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pmc-6022423-1 | A thirty-three-year-old woman was admitted to our clinic at the 37th week of her gestation for delivery with a history of gravidity six, parity two, and abortion three. She had one previous cesarean section delivery. Her preoperative hemoglobin was 10.8 g/dL, prothrombin time (PT) 10.5 seconds, activated partial thromboplastin time (aPTT) 29 seconds, international normalized ratio 2.3, and platelet count 385x109/L. Transabdominal sonography and magnetic resonance imaging displayed total placenta previa, with myometrial invasion to the urinary bladder at the anterior wall of uterus (, ). The patient stated preoperatively that she preferred a conservative approach rather than hysterectomy in case of massive bleeding. After cesarean delivery of a transverse baby through a Pfannenstiel incision and removal of the placenta, a 5-6 cm area of tissue loss was detected at the anterior wall of the uterus and bleeding occurred from the cervix and posterior wall of the bladder. Pelvic packing was applied on the pelvic vessels for 20 minutes, the bleeding sites were sutured with 1.0 polyglactine sutures, and Sengstaken-Blakemore balloon catheter was placed in the uterus before suturing. A stomach balloon was filled with 250 mL saline and an esophageal balloon was filled with 400 mL saline to provide compression on the lower uterine isthmic and cervical bleeds, nevertheless, bleeding continued. Bilateral uterine and hypogastric artery ligations were planned due to hemorrhage. The left external iliac artery was accidentally held and bonded as the left hypogastric artery, which was released within a minute after distinguishing the vessels. Following this mistake, the uterine and hypogastric arteries were ligated on both sides. The patient lost about 2000 cc of blood due to the intraoperative hemorrhage as measured by adding 1650 cc blood in the aspirator and counted gauzes. She received erythrocyte suspension (3 units preoperatively and 4 unites postoperatively) and 3 packs of fresh frozen plasma. The patient had no findings of hypotension or shock at any time. The patient reported severe pain in both legs in the recovery room; it was observed that left dorsalis pedis and femoral artery pulses were absent. Doppler sonography showed a distinct stricture and triphasic flow loss on the left femoral artery. Diagnostic angiography was performed by a cardiologist. After a 6-F introducer sheath was inserted, it was confirmed that both external iliac arteries were occluded (). Intravenous heparin (100 IU/kg) was administered afterwards. A 6-F left internal mammary artery catheter was used with 0.035 hydrophilic guide wires to cross the occlusion. Angioplasty was performed first to the right and then contralaterally to the left external iliac artery with a standard balloon (8x80 mm). A completion angiogram concluded the procedure. The femoral access site managed manually with digital pressure. The balloon catheter was removed after 30 hours. The patient and her child were discharged on the 4th postoperative day with no further events. Informed consent was obtained from the patient. |
pmc-6022434-1 | A 35-year-old African American man was initially sent to our emergency room to evaluate a possible head trauma after a witnessed fall. He complained of frequent falls and leg weakness for 3–4 months. The weakness appeared to be progressive and persistent without episodic worsening. He had to use a cane to compensate but was still able to ambulate. His family members also endorsed cognitive defects over the past few months before admission. These impairments consisted mainly of apathy and withdrawal from social interactions; he used to be fully independent but now stayed at home most of the time. His medical history was only significant for alcohol abuse (three to four cans of beer and red wine daily for 2 years), and his family history was unremarkable.
Physical examinations showed an age-appropriate, alert, and oriented man. He was able to engage in conversations with a paucity of speech and flat affect; he also made eye contact and followed all commands during our evaluations.
There was bilateral weakness with spasticity in all lower extremity muscle groups. The deep tendon reflex was hypoactive with an upward response of the plantar reflex on the left side. He also had a wide-based unsteady gait and poor limb coordination. The remainder of the neurological examination and a general examination were unremarkable.
Initial brain computed tomography (CT) in our emergency room demonstrated a mass lesion occupying the left caudate and extending into his frontal lobe (Fig. ). A brain MRI showed bilateral and symmetric hyperintense signals in the corpus callosum, periventricular white matter, and internal capsule (Fig. ) with an axial fluid-attenuated inversion recovery (FLAIR) sequence with gadolinium enhancement (Fig. ). A cervical spine MRI was negative for cord compression and abnormal signals.
Routine blood tests, as well as human immunodeficiency virus (HIV), syphilis, and thyroid function tests, were unremarkable, and his serum vitamin B12 level was borderline (289 picogram per milliliter). A cerebral spinal fluid sample revealed a mildly elevated protein level (120 mg per deciliter) with a normal cell count (two cells per milliliter) and glucose level (79 mg per deciliter). The sample was negative for cytology, oligoclonal bands, culture, and Epstein–Barr virus DNA polymerase chain reaction (PCR). His urine toxicology panel was negative for common recreational drugs.
The initial impression was an acquired demyelinating white matter disease due to nutritional deficiency. A trial vitamin supplement (500 mg administered intravenously three times a day and 1000 μg of cyanocobalamin administered intramuscularly daily) was given based on his alcohol abuse history, but no symptom improvements were seen during the following week. An inherited condition was thus suspected given the negative workup, the non-response to treatment, and the symmetric involvement in the brain MRI. This suspicion was validated by his peroxisomal fatty acid profile (Table ), and a diagnosis of X-ALD was confirmed according to the identification of a pathogenic mutation in the ABCD1 gene: c.1489 2A>G (g.153005544). Adrenocortical insufficiency was not identified during the evaluation. No seizure activity was witnessed or shown on video-electroencephalography.
His neurological condition deteriorated rapidly. He progressed into a non-verbal, quadriplegic patient dependent on a ventilator within 5 months of the initial encounter, and after 1 year of follow up he had degenerated into a vegetative state. Genetic counseling was offered to his family, and all of his siblings were negative for the ABCD1 gene mutation. |
pmc-6022445-1 | A 73-year-old Japanese man on PD presented with progressive worsening of abdominal pain and cloudy peritoneal fluid. He had high blood pressure, and he started continuous ambulatory peritoneal dialysis (CAPD) because of hypertensive nephrosclerosis 8 years previously. A PD catheter was primarily inserted at the right abdomen, but it was removed and inserted at the left abdomen because of exit site and tunnel infection 5 years previously. He had no past medical history of diabetes mellitus and major abdominal surgery. In the peritoneal equilibration test, his result was high. Bloody ascites was not evident. One year previously, he had been hospitalized for PD-associated peritonitis caused by touch contamination that was treated with intraperitoneal cephazoline and cephtazidime. Bowel adhesion was not noted 5 years previously; however, local bowel adhesions and agglomeration of the intestine were detected by computed tomography (CT) after the identification of PD-associated peritonitis (Fig. , ). The major findings of EPS, such as peritoneal thickening and calcification, were not noted on CT.
On physical examination, his blood pressure was 134/74 mmHg, pulse rate was 76 beats/min, and temperature was 99.7 ° F. He complained of severe pain in the right upper quadrant of the abdomen, and this area was tender on palpation. The exit site was clear. Laboratory tests revealed mild inflammation, with a white blood cell count of 10,100 /μL and C-reactive protein level of 0.9 mg/dL. The peritoneal fluid cell count was increased at 980 /mL. Based on these findings, PD-associated peritonitis was diagnosed. CT showed localized dilation of the intestine, which suggested adhesive small bowel obstruction (Fig. ). As we suspected that the peritonitis might be associated with bacterial translocation from the dilated intestine, he was advised to stop eating and was switched from CAPD to hemodialysis. Additionally, he was treated with intravenous vancomycin and cephtazidime. The PD catheter was flushed once a day to prevent catheter obstruction with fibrin, and the characteristics of the peritoneal fluid were monitored. His abdominal pain was resolved and peritoneal fluid cell count decreased to < 30/mL, and thus, he resumed oral intake on day 8.
After resumption of oral intake, his abdominal pain worsened and his peritoneal fluid cell count dramatically increased to 9600/mL on day 15. The peritoneal fluid became cloudy with a high amount of fibrin and white blood cells (Fig. ). Although he stopped eating again, his abdominal pain did not improve, and fecal material with foul smell was identified from the PD catheter on day 23 (Fig. ). Culture of peritoneal dialysate on admission was negative; however, culture of peritoneal dialysate on hospital day 23 was positive for Enterococcus faecalis and Bacteroides caccae. On CT, the intestinal contents disappeared and the dilated intestine collapsed, indicating that the intestinal contents had leaked into the abdominal cavity (Fig. ). Considering these facts, intestinal perforation was diagnosed, and he underwent ileocecal resection with colostomy creation. Although intra-abdominal adhesion was severe, fibrinous encapsulation of the bowel, which would suggest EPS, was not detected macroscopically during surgery (Fig. ). As indicators of EPS were not evident, the PD catheter was removed. The perforation site was located at the adhesive intestine. The tip of the peritoneal catheter was located in Douglas’ pouch, and it did not injure the adhesive intestine. Pathological examination of the resected specimen revealed inflammatory cells associatet with the peritonitis in the intestinal wall. Intestinal fibrosis, arterial alteration, and tissue calcification were not evident pathologically (Fig. , ). Although his serum beta-2 microglobulin (B2M) level was high (41.05 mg/L), amyloidosis and deposition of B2M were not observed (Fig. -). The postoperative course was uneventful and left arteriovenous fistula surgery was performed on day 42. Since then, he has been on maintenance hemodialysis with no recurrence of peritonitis. |
pmc-6022453-1 | A 5-year-old asymptomatic female was hospitalized in our center for surgical intervention for ALVT with AORCA and BAV. Tracing back to nearly 1 year, this entity of congenital cardiac abnormalities was accidentally detected by a routine echocardiography at a local hospital, with a misleading preliminary diagnosis as BAV with accompanying aortic regurgitation (AR). The patient and her parents reported no evident symptoms, concomitant congenital dysplasia, noteworthy past medical history and family history of inherited cardiac defects. Physical examination showed a grade IV/VI diastolic murmur at auscultatory area of aortic valve. Detailed results from a repeated echocardiography demonstrated: 1) an abnormal tunnel communicating the aortic root and left ventricle, with the opening of aortic segment at the level of the right posterior sinus (0.63 cm at width) and the opening of ventricular segment at the level of membranous interventricular septum (0.43 cm at width); 2) BAV without evident aortic stenosis or AR; 3) the left and right coronary arteries both originating from the left anterior sinus; 4) an enlarged left ventricle (LV) with normal left ventricular function (LV ejection fraction (LVEF) estimated as 65%). The chest X-ray found no significant aberrance (Fig. ). Additionally, a cardiac CTA further confirmed the diagnosis and revealed an abnormal tunnel between the right coronary sinus and left ventricle (Fig. and ). Because the patient presented no obvious symptoms, no medical treatment was perfomed before the surgery.
The patients underwent the surgical repair for ALVT under general anesthesia and cardiopulmonary bypass (CPB). After a median sternotomy was performed and CPB was established, cardiac arrest was achieved using antegrade cardioplegia infusion at the root of aorta for myocardial protection. Subsequent to the horizontal incision at the aortic root, a good view for those anatomical abnormalities was obtained. Except that the AORCA and BAV were confirmed by the surgery, the aortic opening of the tunnel was clearly observed. Near anterolateral commissure the separation between the roots of two leaflets formed into a special ostium with the inner wall of aorta (0.6 cm at width) when the leaflets were closed (Fig. ). The gap between the roots of two leaflets was sutured using 5–0 running polypropylene to turn off the tunnel (Fig. ). Transesophageal echocardiography during the surgery showed no obvious AR. The surgical course went smoothly and the vital signs of the patient remained stable during the operation. No problem during cardioplegia and protection occurred. The CPB time and aortic clamping time were 103 and 75 min respectively.
Nearly 6 h after the surgery, tracheal intubation was weaned sucessfully. During the postoperative period, the continuous intravenous pumping of low-dose dopamine lasted for 7 h without other inotropic drugs administrated. The patient experienced an uneventful recovery without any complication and was discharged home one week after the operation. Echocardiography at discharge demonstrated the trivial AR and normal LV function with a LVEF of 65% (Fig. ). A long-term follow-up for the patient is highly recommended to detect the potential AR and AS caused by BAV in the future. |
pmc-6022486-1 | A 64-year-old woman was diagnosed with locally advanced DTC with invasion to the trachea, esophagus, and left recurrent nerve (Fig. and Fig. (A)). Bronchoscopy revealed that the invasion to the trachea was under half the tracheal circumference, and the distance from the vocal cord to the oral end of the tumor, invasive to the mucosa of the trachea, was 3 cm. Her past medical history included non-insulin dependent diabetes mellitus controlled using insulin injections for a year. She underwent total thyroidectomy with bilateral modified radical neck dissection, followed by a window resection of the trachea invaded by the tumor. A one-stage reconstruction was then performed using an auricular deltopectoral flap. The patient was finally diagnosed with papillary thyroid carcinoma (PTC), pT4aN1bM0, stage IVA, according to the 7th edition of the Union for international cancer control TNM classification of malignant tumors. The operation was macroscopically curative, although a final histopathological estimation of the tracheal margin was positive. Three months after the operation, apart from tracheal anastomosis and the newly emerged lung metastasis, a recurrent tumor was detected outside the left piriform fossa (Figs. and (B)). Therefore, the patient was given 100 mCi of I-131 therapy. No accumulation of I-131 was detected. Nine months after the operation, the patient felt apparent dyspnea and a dull pain in the right shoulder. A CT scan revealed prominent tumor progression in both the neck and the lung, and bone scintigraphy showed bone metastasis in the right scapula (Figs. and (C)). EBRT was performed for the recurrent neck tumor (60 Gy) and the right scapula (36 Gy), and docetaxel was administered once per 3 weeks for 24 months. Docetaxel was temporarily very effective for the local recurrence, although the lung metastasis was remarkably enlarged (Figs. and (D)). Three years after the operation, the patient was started with the newly emerged TKI sorafenib, but because of the progression of lung metastasis, it was terminated in 9 months (Figs. and (E)), although bone scintigraphy demonstrated the disappearance of bone metastasis. Therefore, 45 months after the operation, lenvatinib was started. There are strict regulations regarding the use of lenvatinib at our facility, which must be adhered to (Table ). Within 2 months after the start of lenvatinib, recurrent tumor and lung metastasis was remarkably decreased [partial response (PR), Figs. and (F)], but 1 month later, coughing and dyspnea appeared and XP demonstrated pneumonia. A CT scan demonstrated a pin-hole perforation of the trachea (Figs. and (G)). The symptoms disappeared 1 month after lenvatinib was terminated, and the tracheal fistula naturally closed (Figs. and (H)). Lenvatinib was then restarted, following which the local recurrence decreased and most metastatic tumors in the lung disappeared within 3 months (Figs. and (I)). However, because of the exacerbation of diabetes involving a foot ulcer, the administration was again halted for 2 months, which led to the exacerbation of lung metastasis (Figs. and (J)). After restarting the administration, diabetes, hypertension, and urinary protein as adverse events were well controlled by drugs and nutrition counseling and lung metastasis was controlled; CT scan demonstrated no recurrence in the neck, and bone scintigraphy revealed no bone metastasis (Figs. and (K)). Till the present, lenvatinib has continued to be effective (PR) 1 year and 9 months after the initiation of the drug (Figs. and (L)). Time-course result of patient remedy and effect, including thyroglobulin level, is shown in Fig. . |
pmc-6022698-1 | A 54-year-old Chinese male was referred to our hospital for further evaluation of a liver mass, which was discovered incidentally during routine physical examination in a local hospital. The patient had a 10-year history of hypertension and was diagnosed with diabetes mellitus approximately 5 years before. He denied history of liver cirrhosis and hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. The patient underwent splenectomy 5 years earlier owing to a high-altitude falling accident. No mass was identifiable on abdominal palpation exam. Serum tumor markers (alpha-fetoprotein, CA199, and CA125) were within the normal range. Abdominal ultrasonography (US) revealed a 5 cm iso-echoic lesion that located in the left hepatic lobe near the capsule. A 1.2 cm gallstone was also observed. An abdominal plane-computed tomography (CT) scan revealed an oval, slightly hypodense mass located in segment IV of the left liver lobe measuring 4.5 × 3.3 cm. The lesion had an inhomogeneous enhancement during the arterial phase and diminished enhancement during the portal and equilibrium phases on a contrast-enhanced CT scan (Fig. ). Abdominal magnetic resonance imaging (MRI) showed a slightly hypointense mass on both T1- and T2-weighted images, which appeared slightly hyperintense on diffusion-weighted images. After the injection of gadoxetic acid, the lesion appeared strongly heterogeneous and hyperintense during the arterial phase and relatively hypointense during the portal and equilibrium phases (Fig. ). An indication of a pseudo-capsule was also observed. Partial hepatectomy and cholecystectomy were performed with the suspicion of hepatocellular carcinoma (HCC).
During the operation, the intrahepatic mass was found to be located in segment IV of the liver, measuring 4.0 cm in diameter. It was completely embedded in the liver tissue, and no other mass was found. Postoperative hematoxylin and eosin staining revealed sinusoidal structures and lymphoid tissue hyperplasia. A capsule separating the spleen tissue from liver tissue could be clearly detected (Fig. ), which confirmed intrahepatic splenosis. Detailed immunohistochemical staining showed positivity for CD3 and CD20, specific markers for lymphocyte T cells and B cells, respectively. Meanwhile, the expression of the Ki-67 antigen was quite limited. The polyclonal nature of the lymphocytes and the low proliferation activity further confirmed the benign characteristic of the mass, as malignant tumors are always monoclonal with active proliferation. The patient discharged uneventfully after the operation, and no symptoms of recurrence have been observed during 2 years of follow-up. |
pmc-6022978-1 | The patient is a 43-year-old man, Latin-American, with degree-level education. He attended the medical consultation after his wife noted a two-year history of progressive forgetfulness, mental confusion, disorientation, difficulty finding the right words, changes in mood (basically from being shy to outgoing). He also lost his job for poor performance and was rejected by his friends as a consequence of his new outgoing personality. Concomitantly, he started experiencing sleep changes and apathy, together with anxiety symptoms. Initially he was treated as suffering from major depression, and later as type II bipolar disorder. The treatments failed to change his behavior. The physical examination was completely normal, including pulmonary and cardiac auscultation (normal echocardiogram), except for multiple skin blemishes, mainly on the trunk. Neither he nor his wife recognized his skin changes as abnormal. The blemishes were spread all around his trunk and belly, and changed rapidly under finger pressure ( - right side with blue arrows). The patient was submitted to neuropsychological tests and we provide here a brief overview of the results: he scored 23 points on the Mini-Mental Status Examination and only 15 points on the MOCA test. He scored 30 points on the HAM-D scale and 20 on the Hamilton anxiety scale. The patient was CDR 1 and FAST stage was 5 (moderate disease). In general, the patient performed poorly on all neuropsychological tests, with moderate-to-severe decline in cognitive functions, including declarative memory, attention, and poor language and executive function results. He also presented many emotional disturbances that were negatively affecting his life. No further neurological signs were found. Lastly, neither the patient nor his wife described any stroke-like episodes. He reported no family history of livedo reticularis, stroke, vasculitis, or SS.
Laboratory findings showed undetermined anticardiolipin antibodies, besides the weak presence of lupic anticoagulant. Laboratory studies for venereal disease, human immunodeficiency virus and hepatitis B and C tests, protein C and protein S, C-reactive protein, sedimentation rate, rheumatoid factor, antinuclear factor and other rheumatic testing were completely normal.
The brain MRI () - upper left showed multiple areas of signal changes on cortico-subcortical transition and in the deep periventricular white matter with gadolinium enhancement, consistent with brain ischemia. Imaging also disclosed diffuse cerebral atrophy disproportionate for his age. Brain Perfusion with 99mTc - ECD brain SPECT showed accentuated diffuse hypoperfusion in parietal and frontal areas () - lower left.
Cerebral angiography () revealed slowed distal blood flow of cerebral arteries with decreased vessel diameter and parietal irregularities suggestive of vasculitis. The venous phase was normal, and there was no vascular malformation. The anterior, middle and posterior cerebral arteries in their respective distal segments showed segmental lesions with reduced caliber associated with tortuosity and slowed flow, characterizing a late blush in the territory of the watershed zone. The patient was discharged from the hospital with a diagnosis of SS and the following treatment: acetylsalicylic acid, corticoids and oral anticoagulants.
We obtained the approval of the institution’s ethics committee and the patient’s informed consent form. |
pmc-6023302-1 | We present the case of a 54-year-old female coming to our attention in April 2017 for a single thyroid nodule of 1 cm in its largest diameter, incidentally discovered in the left lobe during an ultrasound US performed for another indication. When the complete biochemical screening (TSH, autoantibodies and Ct) was performed, Ct was found only slightly elevated (40 ng/mL, normal values: 1–4.8), therefore a stimulation test with iv calcium was performed. After stimulation, Ct levels peaked at 1420 ng/mL, indicating surgical treatment. The patient underwent total thyroidectomy and central neck dissection (level VI) on the side of the tumor. The postoperative course was uneventful, with only a slight hypocalcemia recorded in the first postoperative day, which completely recovered 48 hours after surgery when the patient was discharged. Immunohistochemistry performed on the nodule showed the presence of a polilobulated medullary thyroid cancer (MTC) of 1 cm, composed of cells with fused shape with eosynophilic cytoplasm, agglomerated in solid nests with a predominantly expansive growth pattern (A). A histological examination showed that the tumor cells were positive for Ct, Cromogranin A, Synaptofisin, and TTF-1 (B), and negative for the presence of amyloid (not shown). Focal foci of C-cells hyperplasia were spread in the entire gland. In none of the lymph nodes of the central compartment metastases were found.
To perform a more detailed morphological analysis, formalin-fixed paraffin-embedded sections (3-μm-thick) were subjected to antigen retrieval with citrate buffer at high pH, immunolabeled with rabbit monoclonal anti-calcitonin (SP17, Cell Marque) (), and then incubated with appropriate fluorescent secondary antibodies (anti-rabbit Alexa546) from Invitrogen/Life Technologies. As shown in , the tumor cells as well as the C-cells found in the surrounding follicolar parenchima expressed strong intracellular positivity for Ct (A,B), (F) (C).
We next performed immunofluorescence labeling for the RTK receptors ERBB1 (EGFR), using a polyclonal anti-EGFR antibody (Sigma-Aldrich SRL, Milano, Italy), and ERBB2, using the monoclonal humanized anti-ERBB2 antibody trastuzumab, alexa488-conjugated (10 µg/mL), (Genetech-Roche, South San Francisco, CA, USA). The slides were examined and imaged with an inverted Olympus microscope (Olympus Italia, Segrate, Italy) at 40× and 63× magnifications. As shown in A,B, the tumor cells displayed strong punctate positivity for both ERBB1 and ERBB2 receptors, consistent with their localization in intracellular compartments, likely the endolysosomal system. Indeed, double immunofluorescence for ERBB2 and Ct showed a limited overlap of the two proteins, indicating that Ct and ERBB2 were segregated in distinct intracellular compartments.
For electron microscopy, small pieces of fresh tissue were immediately fixed after surgical resection in 2.5% glutaraldehyde, post-fixed with 1% osmium tetroxide, and embedded in epoxy resin. Ultrathin sections were double stained with uranyl acetate and lead citrate and examined under a transmission electron microscope (TEM, CM10 Philips, Eindhoven, The Netherlands). The ultrastructural examination of the tumor nodule displayed heterogeneous spindle-shaped cells containing two distinct classes of tightly packed secretory granules uniformly distributed throughout the cytoplasm (A).
Round-shaped mitochondria (mit) with disorganized cristae were frequently observed (A). Tumor cells containing large, pale-cored secretory granules (LG) were the majority with respect to cells containing small and dense-cored granules (SG). The tumor nodule also contained blood and connective tissue in which cancer cells were scattered. Consistently with other morphological studies [,], a morphometric analysis of granule size and distribution showed two main classes of secretory granules based on their size and morphology (B,C). The small granules (SG) had an electron-dense core and a size ranging from 200 to 400 nm, while the large granules (LG, 300–500 nm in size) were pale-cored. Statistical significant differences in granules’ size (*** p < 0.0001) and morphology might reflect distinct stages of hormonal production [,]. In particular, the mature granules appeared characterized by their uniform and moderate electron density and by their generalized distribution throughout the cytoplasm, while the small electron-dense granules would represent pre-secretory immature granules []. |
pmc-6023324-1 | The subject is a 50-year-old native Canadian woman who resided in an area endemic for LD in eastern Canada. She did not recall an erythema migrans (EM) rash. She developed extreme fatigue and musculoskeletal pain as well as ulcerative skin lesions along with symptoms of formication. Magnification demonstrated filamentous inclusions within the lesions. The subject was seronegative for anti-Bb antibodies excepting two indeterminate IgM bands showing reactivity to the 41-kDa and the 93-kDA proteins, and a weakly positive IgG band showing reactivity to the 41-kDa protein. She was clinically diagnosed with LD by a health care provider in Canada and treated with antibiotics. The subject had discontinued antibiotics three weeks prior to the sampling period, but continued treatment with naturopathic remedies. Despite ongoing treatment with amoxicillin, the subject continues to have persistent symptoms of Lyme disease. |
pmc-6023324-2 | The subject is a 54-year-old Caucasian woman who had a history of outdoor recreational activity in Western Canada including areas in British Columbia that are endemic for LD. She recalled an EM-like rash several years previously, and she did not receive treatment. She developed significant joint pains, muscle aches, headaches, memory loss, fatigue and skin lesions, and she initially tested negative for Lyme disease. She was clinically diagnosed by a Canadian health care provider, and the diagnosis was confirmed later by an American health care provider. She also had positive serological tests for Babesia and Bartonella. She did not have prior knowledge of Morgellons disease, but she did have ulcerative lesions on her face and torso consistent in appearance with the condition. Upon examination with a 50× handheld microscope, filamentous inclusions were observed in her lesions. She has been aggressively treated over the last few years with antibiotic combinations including intravenous ceftriaxone, metronidazole, telithromycin, doxycycline, amoxicillin, ciprofloxacin, tinidazole and atovaquone with little benefit. |
pmc-6023324-3 | The subject is a 63-year-old Caucasian man who had a history of outdoor recreational activity in endemic areas for Lyme disease, including Europe, Western Canada, and the USA (Connecticut and Rhode Island). Although he recalls tick bites, he did not recall an EM rash. The subject developed musculoskeletal pain and extreme fatigue. His wife (Case 4) had an EM rash and a LD diagnosis that prompted him to get tested for LD. He was seroreactive for anti-Bb antibodies, and Bb DNA was detected in serum using PCR technology. He tested serologically positive for Babesia microti and Anaplasma phagocytophylum. He had received ongoing treatment with antibiotics, including doxycycline, clarithromycin, cefdinir, tinidazole, atovaquone, clindamycin and hydroxychloroquine. He was symptomatic and taking doxycycline at the time of sampling. His condition has since improved, but he still suffers from musculoskeletal pain. |
pmc-6023324-4 | The subject is a 53-year-old Caucasian woman and the wife of Case 3. She had a history of outdoor recreational activity in Lyme endemic areas of the USA and Canada. She has a history of tick bites and recalled an EM rash after visiting both Connecticut and Rhode Island. Her symptoms included seizures, neuropathy, palpitations and musculoskeletal pain. She had serological testing for Bb and was initially negative, but she became seropositive after taking antibiotics. She also had positive serological testing for Babesia microti and Anaplasma phagocytophylum. She was symptomatic and taking antibiotics during the time of sample collection. Antibiotics taken included doxycycline, telithromycin, minocycline, clindamycin, clarithromycin, metronidazole, tinidazole, rifampicin, atovaquone, hydroxychloroquine and mefloquine. The subject was taking clarithromycin and cefdinir at the time of sample collection. She is currently asymptomatic. |
pmc-6023324-5 | The subject is a 40-year-old Caucasian woman living in Calgary, Canada, and the partner of Case 6. She is a veterinarian and had a history of work exposure to ticks, and she had also travelled to areas endemic for LD in Europe. She did not recall an EM rash. Her symptoms were primarily musculoskeletal and severe headaches. She was seropositive for Bb and Babesia, and she had been treated with the following antibiotics: doxycycline, clarithromycin, metronidazole and atovaquone. She had been taking doxycycline for one month at the time of sample collection. |
pmc-6023324-6 | The subject is a 42-year-old Caucasian man living in Calgary, Canada, and the partner of Case 5. He is a veterinarian and had a history of work exposure to ticks. He had also travelled to areas endemic for LD in Europe. He did not recall an EM rash. His symptoms were primarily musculoskeletal, severe headaches, memory loss, vision problems and extreme fatigue. He was seropositive for Bb and Babesia, and he had been treated with the following antibiotics: doxycycline, clarithromycin, metronidazole and atovaquone. He had been taking doxycycline for one month at the time of sample collection. |
pmc-6023324-7 | The subject is a 36-year-old Caucasian woman living in Calgary, Canada. She was bitten by many ticks while working as a tree planter in the mountains, but she does not recall an EM rash. In September 1997 she developed profound fatigue, migratory joint pains, peripheral neuropathy and personality changes consistent with depression. She was seropositive for Bb, and she was eventually treated with intramuscular penicillin, amoxicillin, and minocycline over two years. She remains symptomatic despite antibiotic treatment. |
pmc-6023324-8 | The subject is a 39-year-old Caucasian man residing in Calgary, Canada. He has a history of hiking, camping and other outdoor activities in Alberta and Manitoba, Canada, but no known tick bites or EM rash. He complains of joint pain, low back pain and headaches, and he has been treated for sciatica, depression, insomnia, and anxiety. He also has an extensive history of periodontal disease with recurrent gingival infections, and he has received multiple courses of penicillin and amoxicillin over many years. He had positive serological testing for Lyme disease, and he has not been tested for tickborne coinfections. |
pmc-6023324-9 | The subject is a 71-year-old Caucasian woman living in Ontario, Canada and the partner of Case 10. She was 40 years old when she became ill in 1986 with severe flu-like symptoms, fatigue, severe pelvic pain, blurred vision, rib soreness and night sweats. She did not recall a tick bite or an EM rash. The patient had not knowingly visited a Lyme disease endemic area. She consulted six different physicians over a period of four years before being treated with six weeks of doxycycline for what was diagnosed as pelvic inflammatory disease in 1988, and her symptoms transiently improved. She was clinically diagnosed with Lyme disease in 1990 by a physician in Ontario, as the Ontario government’s ELISA test was “negative” for Lyme disease. Over the next 20 years the subject was intermittently treated with doxycycline and her symptoms improved, but never completely resolved, and other symptoms developed such as muscle aches, joint pains, sleep disturbances, bladder and urethral pain, and cognitive impairment. These symptoms waxed and waned over the years. She experienced multiple Jarisch–Herxheimer reactions with repeated doxycycline treatment. The subject’s two children were treated for congenital Lyme disease between 1990 and 2004 and are asymptomatic today. In May 2011, the subject was tested by a CLIA-approved laboratory in the USA and was found to be serologically positive for Lyme disease. |
pmc-6023325-1 | Case 1: An eight-year-old, healthy, African-American female patient presented with her mother at the department of Pediatric Dentistry at Tufts University School of Dental Medicine (TUSDM) complaining of asymptomatic swelling in the labial mucosa of her lower lips. No significant medical history or known allergies were reported. Examination revealed a 0.70 cm silver blue, translucent swelling opposite the right mandibular canine. The mother reported that the swelling started four months before and changed episodically in size and color. They denied any previous trauma or habit of lip biting (). |
pmc-6023325-2 | Case 2: An eight-year-old, healthy, Asian female patient presented with her parents at the department of Pediatric Dentistry at TUSDM for initial dental examination. The patient complained of swelling in her lower lip. No significant medical history or known allergies were reported. Examination revealed a 2-cm translucent swelling in the labial mucosa on the lower lip opposite the left mandibular lateral incisor. Her history revealed that the swelling appeared a long time earlier and did not change in size and color. The parents denied any previous trauma or habit of lip biting (). |
pmc-6023325-3 | Case 3: A four-year-old, healthy Caucasian male patient presented with his parents at the department of Pediatric Dentistry at TUSDM for an emergency, complaining of asymptomatic swelling in the labial mucosa on the lower lip. No significant medical history or known allergies were reported. Examination revealed a 0.60 mm pale pink swelling opposite the right mandibular lateral incisor. It had begun several months before and the parents noticed that it increased in size. The parents confirmed that the patient was in the habit of biting his lip (). All patients reported mild discomfort while eating and speaking. |
pmc-6023335-1 | A 71 year-old woman with a history of hypertension, hypothyroidism, and acoustic neuroma was admitted for right retrosigmoid craniotomy and tumor resection. Her operation was uneventful, with no immediate post-surgical complications. She was discharged on dexamethasone 6 mg daily for 3 days, with tapering doses of steroids over the course of 1 week. Three weeks later, she presented to the hospital with persistent fever and chills, and had experienced occasional headaches for five days. On admission, her vitals were significant with a temperature of 38.5 °C, heart rate of 83 beats per minute, respiratory rate of 14 breaths per minute, and blood pressure of 158/83 mmHg. On examination, she was alert and oriented to person, place, and time. Her right posterior auricular incision site looked clean, with mild erythema but no discharge. Sutures were intact. Neurologic exam did not reveal any focal or meningeal signs. Laboratory studies were significant with a white blood cell count of 8.9 k/μL, hemoglobin of 10.9 g/dL, and a platelet count of 313 k/μL. Urinalysis showed 33 white blood cells, positive leukocyte esterase, and negative nitrates. Urine culture grew more than 100,000 colonies of Klebsiella pneumoniae. She was started on cefepime 2 g intravenously every 12 h for presumptive urinary tract infection. Despite antibiotic coverage for 3 days, the patient continued to have fevers up to 38.7 °C. Given her recent surgical intervention, a computed tomography (CT) scan was ordered, which showed a subgaleal collection overlying the craniotomy site and hypodense areas in the right cerebellum that likely represented postoperative changes. A hypodense extra-axial collection was noted along the right cerebellum. Given the concern for postsurgical meningitis, cefepime was switched to meropenem 2 g every 8 h, and vancomycin 1 g every 12 h was added to her antibiotic regimen. The patient showed a rapid clinical deterioration, with the development of nuchal rigidity, altered mental status, and seizures in the next 24 h. She underwent a lumbar puncture, which evidenced an opening pressure of 30 cm H2O. Cerebrospinal fluid (CSF) analysis showed 800 white blood cells/mm3 with 90% neutrophils, low glucose (31 mg/dL), and high protein (115 mg/dL). The smear for acid-fast bacilli in CSF was negative. CSF Cryptococcus antigen was also negative. The FilmArray® meningitis/encephalitis panel did not identify any organisms. Emergent magnetic resonance imaging (MRI) was ordered, which showed diffuse leptomeningeal enhancement and moderately dilated ventricles. Fluid layering within the bilateral occipital horns was noted, as there were concerns of ventriculitis. Additionally, a 1 cm right cerebellar extra-axial collection was seen (A,B). The patient was immediately taken to the operating room for the placement of an external ventricular drain. Intrathecal colistin and vancomycin were initiated afterwards. Follow-up CSF analysis 48 h later showed normalization of white blood cell count (2 cells/mm3); however, low glucose and high protein persisted. Lactic acid from CSF was elevated (35 mg/dL). Bacterial and fungal cultures from the blood and CSF did not show any growth. Intraventricular antibiotics were discontinued after 48 h, and the patient continued with meropenem and vancomycin intravenously for 2 weeks. Despite antibiotic therapy, the patient’s mental status did not improve significantly, and the fevers continued intermittently. Further studies that included serum galactomannan and (1→3)-β-d-glucan were negative. A repeat MRI showed persistent leptomeningeal enhancement at the cervicomedullary junction at the skull. Extra-axial collection adjacent to the retrosigmoid craniotomy was again noted. A CT scan of the chest, abdomen, and pelvis was ordered to rule out other potential sources of infection, but imaging was unremarkable. On further questioning, the patient’s daughter stated that her mother was in India and Nepal three months prior to the initial craniotomy, where she was working as a volunteer in a clinic and was exposed to patients with tuberculosis (TB). The patient had a history of a positive purified protein derivative (PPD), but was never treated for latent TB. Given her epidemiologic risk factors, MRI findings and clinical deterioration, the patient was started on isoniazid, rifampin, pyrazinamide, and levofloxacin for the treatment of presumptive tubercular meningitis. However, after one week of treatment, no clinical improvement was noted, and she was taken to the operating room for exploration. The patient underwent midline limited suboccipital craniotomy and C1 laminectomy. Clear pus was noted in the area of the foramen magnum, foramina of Magendie, and posterior to the upper cervical cord, with evidence of pachymeningitis of the pia of the upper cervical cord and both cerebellar tonsils. The subdural empyema was evacuated and samples were sent for cultures. A biopsy of the arachnoid tissue was obtained. Intra-operative frozen section revealed chronic mixed inflammatory, but no granulomas. Two days later, histopathology reported fungal elements. Immunohistochemistry for Aspergillus was strongly positive (A,B). Toxoplasma, acid-fast bacilli, and gram stains were negative. Tissue sample was sent to the University of Washington in Seattle, WA for fungal PCR. Anti-tuberculosis treatment was discontinued and the patient was started on liposomal amphotericin 5 mg/kg daily and voriconazole intravenously 6 mg/kg every 12 h as a loading dose, and then 4 mg/kg every 12 h for maintenance. Five days later, tissue real-time PCR came back positive for Aspergillus fumigatus. Amphotericin was discontinued and the patient was kept on voriconazole. The patient’s mental status improved markedly over the following days. The fever subsided as well. Treatment with intravenous voriconazole was eventually transitioned to oral voriconazole 250 mg every 12 h to complete 3 months of therapy. The voriconazole level at 2 weeks of treatment was 2.6 μg/mL, which was within the therapeutic range for central nervous system (CNS) aspergillosis (reference range 2–5 μg/mL). The patient was later transferred to a rehabilitation facility for physical therapy. At the four month follow-up, the patient was fully alert, and her verbal communication was almost back to her baseline. No focal or meningeal signs were noted on examination. A brain MRI was repeated and showed complete resolution of leptomeningeal enhancement, with no collections. |
pmc-6023385-1 | A 48-year-old man originally from Mexico presented to the Infectious Disease clinic with constipation and painful defecation in the last 4 weeks. He had noticed streaks of blood on the toilet paper after wiping. He had a 5-year history of HIV infection treated initially with Tenofovir/emtricitabine/efavirenz that was recently switched to abacavir/lamivudine/dolutegravir. His latest CD4 count was 304 cells/uL and his HIV viral load was undetectable. He was MSM (men who have sex with men), but denied unprotected sex in the last 3 months. His vital signs were within normal limits. He weighed 77.1 kg and did not report any significant weight loss. His abdomen was soft, nontender and non-distended. Bowel sounds were normoactive. Rectal exam was normal. Laboratory studies showed hemoglobin of 14.1 g/dL, leukocyte count of 4.7 K cells/uL and platelet count of 246 K cells/uL. Chemistry panel was significant only for mildly elevated alkaline phosphatase (142 U/L). RPR (rapid plasma reagin) was negative. Stool culture was negative for Salmonella, Shigella, Aeromona and Plesiomona. Campylobacter antigen and Escherichia coli shigatoxins were not detected. Ova and parasites were not isolated in stool studies. He underwent rectal swab for gonorrhea and chlamydia PCR, which gave negative results. Given unrevealing work-up, the patient was referred to Gastroenterology for endoscopic evaluation. Colonoscopy showed moderate inflammation characterized by congestion, erythema and friability of the rectal mucosa. Shallow ulcerations were noted only in the rectum (). The rest of the colon did not show any abnormalities. Histopathology examination of rectal tissue disclosed a mucosa with increased lymphoplasmacytic and neutrophilic infiltrate in lamina propia. Acute cryptitis and focal crypt abscesses were noted, along with erosions and few poorly formed granulomas (). Immunohistochemistry for HSV1, HSV2, and CMV was negative. Tissue AFB (acid-fast bacilli) staining did not show any organisms. AFB smear in stool was negative; however, two weeks later, stool culture grew Mycobacterium sp. that was further identified as Mycobacterium avium-intracellulare complex by DNA probe. No susceptibility testing was performed. Rectal tissue culture did not grow any organisms. To complete the work-up, a chest X-ray and quantiferon gold were ordered. The results were unremarkable. The patient was started on azithromycin 500 mg daily, rifabutin 300 mg daily and ethambutol 1200 mg daily. At 2-month follow up, the patient reported complete resolution of his symptoms. Four months later, rifabutin was discontinued. The plan was to continue with azithromycin and ethambutol for six additional months to complete a total treatment course of one year. |
pmc-6023516-1 | A 67-year-old man from India, who was recently diagnosed with latent tuberculosis, presented to an outside hospital and was admitted for six days with generalized fatigue and hypotension. On presentation, he reported a 2-week history of generalized fatigue with systolic blood pressures in the 60s, as recorded at home. He also reported a 30-pound weight loss which was attributed to diuretic use and dietary changes in the setting of congestive heart failure. With these complaints, his losartan (angiotensin receptor blocker) dose was reduced, which was ineffective in alleviating his symptoms. His history was notable for an LTBI diagnosed three months prior to presentation, for which he was being treated with INH (300 mg daily) and pyridoxine. He had been treated for 11 weeks by the time he presented, and was noted to tolerate the therapy well for at least four weeks without changes in dietary or sleeping habits, per documentation by his primary care provider. His medical history was otherwise notable for atrial fibrillation, beta thalassemia, and tachycardia-induced cardiomyopathy with reduced ejection fraction. He had no known history of liver disease or diabetes. His other medications included apixiban, metoprolol, furosemide, losartan, and hydroxyzine (for insomnia). He had no prior history of heavy alcohol consumption or recreational drug use, and he worked in the electronics and computer industry. There was no family history of cirrhosis or other liver disease.
His initial workup was notable for elevated liver function tests, as shown in . A computed tomography scan of the abdomen demonstrated no intrahepatic biliary dilation and no apparent fatty change. An abdominal ultrasound revealed a simple cyst and heterogenous echotexture, with mild subcapsular nodularity. Based on his workup, his liver dysfunction was postulated to be drug-induced liver injury from INH or apixaban. Both medications were discontinued. He was discharged for outpatient management. However, follow-up laboratory testing indicated an increasing bilirubin, which resulted in readmission to the hospital. A liver biopsy was considered but not performed, as his bilirubin levels began to downtrend.
One week later, the patient experienced a syncopal episode while having a bowel movement, and was admitted to a different hospital. He presented with altered mental status and generalized pruritis. Laboratory data revealed worsening liver function () and acute kidney injury, for which he was treated with albumin, midodrine, and octreotide. His pruritis improved with the introduction of cholestyramine.
Autoimmune serologies, including antinuclear antibody, antimitchondrial antibody, and anti-smooth muscle antibody, were negative. Viral hepatitis serologies were negative. HIV infection was ruled out. The patient’s acetaminophen level, urine toxicology screen, and serum ferritin level were within normal limits. A transjugular liver biopsy was performed and demonstrated cholestatic hepatitis, thought to be drug- or toxin- related. His mental status initially improved with lactulose, but worsened thereafter, prompting a transfer to our hospital for consideration of liver transplantation for acute liver failure, about six weeks after initial presentation.
Physical examination at time of transfer was remarkable for jaundice, icteric sclera, and altered mental status. He was somnolent but arousable to noxious stimuli, oriented only to self, intermittently following some commands, and had notable asterixis. He had an irregular rhythm and a murmur on cardiac examination, vesicular breath sounds, and a benign abdominal examination. He was noted to have Grade III hepatic encephalopathy in the setting of acute liver failure, and was admitted to the intensive care unit before being listed for liver transplantation as Status 1A. On day four in the hospital, he underwent orthotopic liver transplant surgery, and was extubated on post-operative day one. He was transferred to the floor on post-operative day three, but subsequently suffered a sudden aspiration event resulting in a pulseless electrical activity and fatal cardiopulmonary arrest. |
pmc-6023626-1 | Patient 79 years old, female, who came to the Emergency Department with complaints of
epigastralgia with two weeks of evolution and aggravation last night. She denied
another accompanying symptomatology. As personal background, she presented
unmedicated dyslipidemia and intrinsic asthma with onset in adulthood. She was
medicated with bronchodilators and an association of a B2-agonist with inhaled
corticosteroids at low doses.
The objective examination showed tachycardia, confirmed on electrocardiogram with
sinus rhythm of 125 beats per minute. Analytically had leukocytosis (13.2 x
103/uL) and eosinophilia (2.8 x 103/uL or 23%), C-reactive
protein (0.8 mg/dL) and elevation of markers of myocardial necrosis (troponin I of
7.6 ng/mL). Transthoracic echocardiography revealed severe left ventricular systolic
dysfunction with an ejection fraction estimated at 30-35%, ventricular septal
hypocontractility and an increase in the concentric thickness of the ventricular
walls.
Valvular disease was not evident. It was placed as a first hypothesis that it was an
acute coronary syndrome, so anti-ischemic therapy with double platelet
antiaggregation, enoxaparin, was started and the patient was assigned to an invasive
strategy. Coronary angiography did not reveal epicardial coronary disease. After
this, the diagnosis of eosinophilic myocarditis in a patient with a known atopic
component was likely. She was admitted to hospital for treatment and study.
Neuro-humoral, beta-blocker and diuretic therapy were initiated, maintaining
aspirin.
On the third day of hospitalization, cardiac magnetic resonance was performed which
identified subepicardial foci of edema and late enhancement in the left ventricular
myocardium (); she also showed a small
pericardial effusion in the free wall of the right ventricle. The ejection fraction
was quantified by 33%. On the same day, she underwent an endomyocardial biopsy and
collection of right ventricular infarct fragments, which confirmed the diagnosis of
eosinophilic myocarditis (). Systemic
corticosteroid therapy was started with intravenous prednisolone (1 mg/kg/day) with
progressive improvement of general condition. On the 12th day of hospitalization,
the echocardiogram showed a slight improvement in left ventricular global systolic
function (ejection fraction estimated at 35-40%). She was discharged to home with
prednisolone in weaning, and with follow-up consultation of cardiology and
autoimmune diseases.
The autoimmune serological study was negative. After seven months of corticotherapy,
the echocardiogram showed a significant improvement (ejection fraction estimated at
45-50%), and a decrease in concentric hypertrophy. |
pmc-6023661-1 | In 2006, a 44-year-old woman developed a mass on the left breast with no other clinical symptoms. Excisional biopsy revealed invasive ductal carcinoma. Modified radical mastectomy for breast cancer was then conducted. The postoperative pathological report indicated no evidence of residual cancer and no lymph node involvement (0 of 10). Immunohistochemical analysis showed positive expression of ER (approximately 60%) and PR (approximately 30%) but negative expression of human epidermal factor receptor 2 (HER2). The clinical stage was T1N0M0 (IA). Six cycles of cyclophosphamide + adriamycin + fluorouracil (CAF) chemotherapy were administered. Following CAF chemotherapy, the patient was given toremifene ET until the disease progressed (i.e., relapsed) in 2010.
In June 2010, a tumor was found in the right lower lobe of the lung during routine follow-up. A wedge excision biopsy was conducted, and the tumor was determined to be metastatic lung cancer secondary to breast cancer. Immunohistochemical analysis results were similar to those of the original primary tumor (ER+, approximately 70%; PR+, approximately 30%; and HER2+, 0%). After undergoing an ovariectomy, the patient began exemestane treatment to control the disease.
In March 2014, the patient complained of severe stimulating dry cough. Computed tomography (CT) identified metastases in the lungs and the mediastinal lymph nodes. Meanwhile, a left renal mass was found and was considered to be malignant. However, the patient did not complain of hematuria or flank pain and refused a biopsy to obtain a definite pathological diagnosis. From April 2014 onward, several chemotherapy regimens were employed sequentially to control the disease, but all eventually failed. These regimens included paclitaxel combined with capecitabine, vinorelbine combined with epirubicin, gemcitabine combined with cisplatin, and pemetrexed monotherapy. In August 2015, the patient's symptoms became more severe, and the patient presented with bloody phlegm. Multiple bone metastases were subsequently confirmed via single-photon emission computed tomography (SPECT).
To obtain real-time information about the tumor to inform subsequent treatment, a biopsy was recommended, and the patient consented. A CT-guided needle biopsy of the metastatic lesion in the left lung was performed. Lung metastasis of the breast cancer was confirmed (Fig. ). Interestingly, the immunohistochemical analysis showed increased expression of ER (approximately 90% +). On the basis of these findings, the patient began to take the selective ER downregulator (SERD) fulvestrant (500 mg) and zoledronic acid (4 mg) injections starting on August 19, 2015. Two months later, the subjective symptoms (i.e., dry cough and bloody phlegm) were markedly improved, and a partial response was achieved according to the RECIST criteria (Fig. ). Remarkably, the left renal mass also shrank, which confirmed the original metastatic diagnosis (Fig. ). No significant side effects were observed during the treatment administration of fulvestrant. The patient kept taking an intramuscular injection of fulvestrant (500 mg) every month until December 20, 2016, and CT results showed that the tumor had been stable for 16 months.
The patient decided to stop taking fulvestrant in late December 2016 and also refused to undergo any medical examination until the patient developed a severe cough in November 2017. Meanwhile, intracranial metastases were found by magnetic resonance imaging (MRI). The patient refused to participate in any clinical trials and decided on apatinib (250 mg/day), a vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR-TKI), as the main treatment. Although the cough was relieved, the patient died of epilepsia gravior, which we believed to be due to brain metastases, on November 1, 2018. |
pmc-6023666-1 | A 48-year-old woman noticed a palpable mass in the distal phalanx of her left ring finger with a medical history of enchondroma in the same location. Ultrasound examination revealed an exophytic hypoechoic mass that was connected to the medullary cavity through the interrupted bone cortex. No obvious blood signals or calcification were found in this area (Fig. ). It is difficult to characterize or classify the mass by traditional ultrasound. And a mass located close to the bone was described in our ultrasound diagnostic report. |
pmc-6023666-2 | A 25-year-old woman underwent ultrasound examination for a palpable mass in the middle phalanx of her left ring finger. A hypoechoic mass of 20 mm diameter was found. The boundary of the mass was unclear and punctuate or patchy hyperechoic calcification was present in the mass. The bone cortex was involved, with a broken continuity. In addition, a point-like blood signal was observed on switching to Doppler mode (Fig. ). Notably, the pathology report showed active proliferation in the tumor cells. A mass with bone erosion was diagnosed. |
pmc-6023669-1 | A 59-year-old man presented to our institution in September 2014 with a 2-month history of progressive dysphagia, without hoarseness. He had smoked 60 cigarettes per day for 40 years and had been a heavy alcohol drinker for 40 years. For the last 9 years, he had had hypertension, and had been diagnosed with type 2 diabetes over 1 year ago. He had no prior malignant disease or distant metastases.
On physical examination, the neck and supraclavicular lymph nodes were not palpable. No significant abnormal values were detected in the blood count or in serum and biochemical analysis. Iohexol swallowing revealed a malignant-appearing structure in the inferior-thoracic region. Endoscopic assessment revealed a lesion of mucosal hyperplasia forming a luminal stenosis 36 cm from the incisor teeth, which rendered it difficult for the gastroscope to pass through it. Biopsy of the lesion demonstrated an esophageal MEC. On computed tomography (CT) scanning, the tumor was deemed to be resectable (Fig. ). As the patient was found to be medically fit for an esophageal resection, this surgery was performed.
Esophagectomy, 2-field (upper abdominal and mediastinum) lymphadenectomy, and esophagogastrostomy through the esophageal bed were performed on the tenth day of hospital admission. The resected esophagectomy specimen contained a fungating tumor that measured 45 and 40 mm in the longitudinal and cross-sectional dimensions.
Histopathology showed that most tumor tissue was composed of epidermoid cells that were arranged in nests. In addition, keratin pearl formation was identified. Columnar mucus-secreting cells and intermediate cells in small areas that formed tube-like structures with invasive growth were confirmed by hematoxylin and eosin (HE) staining (Fig. ). Immunohistochemically, the tumor was found to be positive for p-63 (Fig. ), and CK5/6 (Fig. ), using the EnVision system (Agilent, Santa Clara, CA) to identify epidermoid cells. Mucus-secreting cells were identified using Periodic Acid-Schiff staining (Fig. ). Based on immunohistochemistry results, the tumor was diagnosed as a poorly differentiated esophageal MEC. According to the esophageal cancer TNM (tumor, node, metastasis) staging system (American Joint Committee on Cancer/International Union for Cancer Control staging system, 2010), the pathological stage was IIIb: T3N1bM0. The tumor dimensions were 45 × 40 × 15 mm. The tumor invaded the outer membrane of the esophagus. All resection margins were negative for tumor involvement, and 3 of 12 lymph nodes from the upper abdominal and mediastinum showed signs of lymphatic metastasis.
One month after surgery, radiotherapy combined with chemotherapy consisting of paclitaxel and cisplatin was provided. Four additional cycles of chemotherapy were administered; the regimen consisted of paclitaxel (200 mg/m2 on day 1 for 3 hours) plus cisplatin (30 mg/m2 per day for 3 days) repeated for 3 weeks. On the last day of the first chemotherapy cycle, radiotherapy against large chest irregular area, including the entire esophageal bed and the mediastina, was provided to the patient, beginning 30 minutes after the end of cisplatin infusion. The total dose for 95% of the planning target volume (PTV) was 50.4 Gy/28 fractions, and for 95% of the PTV for involved lymph nodes (PTVnd) was 56 Gy/28 fractions. No significant complications occurred after administration of adjuvant radio-chemotherapy. The patient was followed up with no evidence of recurrence for 17 months after surgery.
Seventeen months after surgery, an esophageal CT scan revealed that the esophageal wall was evenly thickened (Fig. ). However, endoscopic assessment revealed no evidence of recurrence. Further esophageal CT scans at 19 and 31 months postsurgery also showed a thickened esophageal wall (Fig. ); however, endoscopic assessment still revealed no esophageal stricture and no evidence of recurrence at 31 months after surgery. The patient was alive with no dysphagia and no evidence of recurrence for over 39 months. |
pmc-6023673-1 | This patient was a 55-year-old man who had consulted at a local hospital for incidentally discovered AF. After being treated with amiodarone for a year, his electrocardiogram (ECG) remained abnormal. Then, he was transferred to the cardiovascular department of our hospital. He had no symptoms such as chest congestion, dizziness, or fatigue, nor did he exhibit symptoms of metabolic syndromes as tachycardia, trembling, or hyperhidrosis. Radiofrequency ablation was performed to treat his AF. The ECG recovered, but the laboratory tests showed TSH 8.9 mU/L (RR, 0.27–4.2), FT3 6.61 pmol/L (RR, 3.6–7.5), and FT4 33.47 pmol/L (RR, 12–22). He ignored the suggestion to consult an endocrinologist. Three months later, the AF recurred, so he received radiofrequency ablation again. Nine months after the patient was discharged from the cardiovascular department, he was referred to our outpatient division for tachycardia, tremors, and thermophobia. At that time, the hormonal examination implied thyrotoxicosis, with a positive result for the TSH receptor antibody (FT3 34.34 pmol/L, FT4 > 100 pmol/L, TSH 0.755 mU/L, TRAb 15.28 IU/L). After administration of thyrozol 10 mg twice a day for 4 months, his symptoms resolved, and his thyroid hormone levels returned to within normal ranges; however, his TSH level was markedly increased. It was suggested to the patient that he should consult an endocrinologist for further examination of the inappropriate secretion of TSH due to central hyperthyroidism. On physical examination at admission, the patient was 172.0 cm tall and weighed 73 kg (body mass index, 24.7 kg/m2). His blood pressure was 135/80 mm Hg, and his pulse was 75 beats/min. The thyroid gland was diffusely enlarged, and ultrasonography of the thyroid revealed a rich vascular supply with a nodule located in the left lobe. Fine needle inspiration biopsy suggested the nodule was benign. The computer perimetry suggested a defective visual field. Magnetic resonance imaging (MRI) of the sella region revealed a pituitary tumor measuring 2.3 × 1.7 × 2.2 cm3 in the sella, involving the cavernous sinuses and extending into the suprasellar cistern (Fig. ). Based on these data, we diagnosed the patient with TSH-producing pituitary macroadenoma and central hyperthyroidism. One week after diagnosis, in May 2014, total resection of the pituitary macroadenoma was performed through transsphenoidal neurosurgery. Upon immunohistochemical examination, the resected pituitary adenoma cells exhibited positive staining with the TSH and PRL antibodies, and the percentage of positive Ki-67 was less than 2%, suggesting that the tumor was benign (Fig. ). After surgery, his TSH levels and thyroid hormone levels remained within the normal ranges. His serum thyroid hormone levels increased beyond the normal ranges 1 year later (TSH 0.223, FT3 11.56, FT4 36.36), although no residual tumor was apparent on the MRI. Positive results were obtained for TRAb, and both TgAb and TPOAb were elevated beyond their normal ranges (TRAb 5.62 IU/L, TgAb 32.79 IU/L, TPOAb 14.13 IU/L). The patient was administered thyrozol 10 mg/day, and his thyroid function tests remained clinically acceptable during 3 years of follow-up. Repeated pituitary MRIs showed a possible mass in the pituitary, suggesting tumor recurrence. In addition, recent ultrasonography showed that the thyroid nodule remained the same size. |
pmc-6023680-1 | A 66-year-old man with a history of left knee osteoarthritis and varus deformity was scheduled to undergo TKA at our hospital. The left lower extremity was prepped using a topical solution, which was to disinfect skin 2 times with chlorhexidine alcohol skin disinfectant (mainly consist of 4.5 g/L chlorhexidine acetate and 70% alcohol). Let the skin air dry, and then place the iodophor-impregnated antimicrobial incise drape on the operation area, which included application of an iodophor-impregnated antimicrobial incise drape. Draping was performed using standard aseptic procedure.
Subsequently, surgery was performed using conventional surgical procedures. At the end of the operation, the skin incision was sterilized again and sutured. Upon removal of the adhesive drape by delicate peeling and warm saline lavage, a large area of the skin avulsion happened. The extensive punctate hemorrhage was visible (Fig. ). The skin avulsion was in the posterior part of the patient's left crus. The avulsion area was approximately 6.5 × 30 cm.
Petrolatum gauze was used to dress the areas of epidermal avulsion. Routine postsurgical dressing (gauze, cotton pad, and bandage) was applied to the incision. On postoperative day 2, an initial dressing change was performed. We consulted with doctors from other relevant departments regarding the avulsion injury who advised on the applicable treatment measures. Based on these measures, we asked the patient to raise the affected leg and keep the wound dry. Sulfadiazine cream was applied to the area of epidermal avulsion. Dressing changes were performed daily. On postoperative day 3, oral cefixime therapy of 100 mg bid was initiated as part of the anti-infection treatment. On postoperative day 4, the light yellow liquid exudes and the localized inflammatory response was visible (Fig. ). On postoperative day 7, the exudate decreased and the inflammatory response was reduced. There was no evidence of infection (Fig. ). On postoperative week 2, the wound was dry, and there was no exudate and no obvious inflammatory reaction (Fig. ). The patient was discharged from hospital on postoperative 2 weeks and was required to change the dressing every 3 days until the avulsion area was dry. After 6 weeks of treatment, the avulsed wound showed no signs of infection and had undergone re-epithelialization (Fig. ). |
pmc-6023702-1 | An 82-year-old male patient was originally admitted to the hospital for difficulty in urinating spontaneously on November 24, 2014. The patient was diagnosed with prostatic adenocarcinoma after transurethral resection of the prostate (TURP) and postoperative pathological examination (Fig. ). In addition, a SPECT/CT scan revealed multiple bone metastases (Fig. ). Initial PSA and free PSA (FPSA) levels were 54.54 and 2.63 μg/mL, respectively (Fig. A). The patient exhibited poor tolerance to radiotherapy and chemotherapy, possibly due to advanced age or pacemaker implantation; therefore, immune therapy of alloreactive CTL was selected as a treatment option.
The patient received the first two cycles of ACTL treatment from December 16, 2014 to February 10, 2015. His PSA levels significantly decreased from 54.54 to 1.35 μg/mL after 28 cycles of continuous ACTL immunotherapy, to undetectable levels of <0.003 μg/mL on May 12, 2016; similarly, immediately after completion of ACTL therapy the FPSA levels were down from 2.63 μg/mL to undetectable levels of <0.01 μg/mL. The PSA and FPSA level remained stable in subsequent days. All the changes in PSA and FPSA are plotted in Fig. B, and each test was performed in the same laboratory. Importantly, there were few bone metastatic lesions detected by the SPECT/CT scan in December 2016 (Fig. ). Similarly, no metastatic lesions were detected in other organs, including the lung, liver, and the brain, by the PET-CT scan. Importantly, the patient remains alive after receiving 2 years of immunotherapy, despite being initially diagnosed with metastatic lesions at multiple sites of the body (Fig. ). Conversely, the withdraw of the ACTL immunotherapy was accompanied by a gradual increase in PSA levels in the patient from being undetectable (<0.003 μg/mL) on May 12, 2016 to 1.08 μg/mL on April 6, 2017 (Fig. ). Unfortunately, the ACTL immunotherapy was not applied again because of the expensive cost and lack of proper blood supply.
It is worth noting that there was no apparent cardiovascular system-related symptom or graft-versus-host disease (GvHD) detected in the patient over the course of the immunotherapy treatment, despite the patient being diagnosed with high blood pressure and Type II diabetes at the beginning the administering immunotherapy. |
pmc-6023704-1 | The patient was a 72-year-old man who was followed up for persistent pain in the left side of the waist for 2 years, radiating to the left hip. The history of schistosomiasis was 40 years, and with hypertension 1 year. On physical examination, he had pain on movement of the spine with bilateral Grade IV motor strength in both lower extremities. There was not numbness in both feet and ankles with normal ankle reflexes bilaterally. There was a normal knee reflex bilaterally. There was no obvious bulge in the bilateral kidney region, and the left lateral kidney region knocks out to be positive for pain. The neurological symptoms were ascribed to the compression of the spinal cord and nerve roots by an expanding mass partly protruding into the vertebral canal.
Magnetic resonance imaging (MRI) was performed that the left side of the vertebral body and the left peritoneum showed an elliptical abnormal signal shadow, which showed a dumbbell growth. The MRI scan showed an area of increased signal intensity on T2-weighted images in the T12-L4 paravertebral region. At discovery, on the left side of the L1 vertebral body, there was a slightly longer T1/T2 signal, with a size of 8.6 × 8.4 × 12.4 cm (Fig. ). The boundary was clear, and the enhanced scan showed an uneven separation. The lesion protruding into the erector spinae muscles and behind the retroperitoneum are connected to the lesion in the vertebral canal through the intervertebral foramen, and the spinal cord was compressed and the boundary was clear. And the computed tomography (CT) showed that bone destruction can be seen on left lateral transverse process of L2, and the left kidney was significantly compressed (Fig. ).
The patient was treated with surgical resection of the total tumor, followed by the spinal internal fixation of L1 to L2 with pedicle screws. A posterior approach was selected for decompression. Intraoperatively, 2 lumps measuring 10 × 9 × 8 cm and 8 × 6 × 3 cm were visible in the focal region. They were well circumscribed and completely resected (Fig. ). Total laminectomy was performed for L1 and L2. On histopathological examination, the gross specimen consisted of ragged pieces of pale-tan, slightly gelatinous material admixed with blood clot. Microscopic examination of the formalin fixed paraffin-embedded specimen showed the presence of a lobulated neoplasm in a prominent extracellular myxoid matrix. The neoplastic cells were composed of syncytial cords of “physaliphorous cells” that contained abundant pale septated and vacuolated clear to bubbly cytoplasm with mild nuclear pleomorphism. Overt mitosis was not identified. Immunohistochemical examination showed that the lesional cells were positive to CK(+++), S100(++), CD65(+), neuron-specific enolase(++), epithelial membrane antigen (+++), and vimentin(+++). The coexpression of epithelial and mesenchymal immunohistochemical markers supported the notochordal lineage of the lesional cells. Ki67 was 3%+ in the lesional cells. The above histomorphological features in conjunction with the immune-phenotype observed confirmed the diagnosis of chordoma.
No heavy ion radiotherapy was performed because the tumor massively invaded into spinal canal and foramen, compressing the spinal cord and nerve root directly. After 5-month follow-up, we find the recurrence in the original lesion through the post-operative CT (Fig. ). In consideration of the huge and complex recurrence, we did not have second operation. At the 15-month follow-up, the patient was dead after a lot of times revisit by various doctors. |
pmc-6023720-1 | The 33-year-old right-handed male patient, with no history of brain damage had suffered from a stroke. Brain magnetic resonance imaging (MRI) revealed an infarction lesion in the left frontal lobe, insula, and basal ganglia (Fig. A). 14 months after stroke, the patient had aphasia only without limb paralysis; thus, he received a 5-month speech therapy composed of spontaneous speech, auditory comprehension, repetition, naming, writing, reading training, and calculation. The speech therapy was carried out for 1 hour per session, for twice a day and 5 days a week. Moreover, the Aphasia Battery of Chinese (ABC) and Boston Diagnostic Aphasia Examination (BDAE) were used to evaluate the language function and the severity of aphasia before and after the speech therapy. Briefly, ABC is a modified Western Aphasia Battery (WAB) adapted to the Chinese culture, which is currently the most extensively used scale in China for aphasia assessment, with well-established reliability and validity.[ Informed consent was given and the experiment was approved by the Ethics Committee of Jinan University First Affiliated Hospital in Guangzhou, China.
The results suggested that the patient had attained certain improvements in his language function (spontaneous speech: 69.8 percentile, auditory comprehension: 66.4 percentile, repetition: 64.0 percentile, and naming: 84.8 percentile). Besides, the severity of aphasia was rated at level 2 before the speech therapy. After the speech therapy, further language functional improvements were achieved (spontaneous speech: 81.1 percentile, auditory comprehension: 69.4 percentile, repetition: 72.0 percentile, and naming: 84.8 percentile), and the severity of aphasia was rated at level 3.
Diffusion tensor imaging (DTI) was carried out before and after the speech therapy, respectively. In addition, an 8-channel head coil equipped on a 3.0 T American GE Discovery 750 MRI with single shot echo-planar imaging was used for the acquisition of DTI data. A total of 47 contiguous slices parallel to the anterior commissure–posterior commissure line was acquired for each of the 25 noncollinear diffusion sensitizing gradients. Specifically, the imaging parameters were as follows: TR/TE = 5000 ms/68.0 ms, acquisition matrix = 96 × 96, reconstructed to matrix = 128 × 128 matrix, field of view = 25.6 × 25.6 mm2, b = 1000 s / mm2, NEX = 1, slice thickness/slice spacing = 3 mm/0 mm. It took 135 seconds for DTI data acquisition. Besides, the corpus callosum was tracked using the self-prepared software package (Functool 9.4.05a). Fiber tracking was initiated at the center of a seed voxel with a fractional anisotropy (FA) of >0.18, apparent diffusion coefficient of >0.01, and the maximum steps of 160.
Results of the follow-up DTI fiber tracking demonstrated that the fiber pathway between the splenium of corpus callosum and the left superior temporal gyrus (Wernicke's area) had been established. In addition, the fiber connections between the genu of corpus callosum and the right inferior frontal gyrus (the mirror region of Broca's area) were increased (Fig. B). |
pmc-6023823-1 | A 61-year-old man who presented with progressive abdominal distention for 8 days was admitted to a local hospital on Feb 23, 2014. Gastroscopic examination and biopsy specimens were evaluated in the local hospital. Histopathological findings showed a suspected diagnosis of squamous-cell carcinoma in the body of the stomach.
On Feb 27, 2014, the patient was transferred to our hospital for further management strategy. Physical examination showed that right upper quadrant pain and tenderness were present and no peristaltic waves. The rest of the physical was unremarkable. A detailed medical history was obtained. The patient lost weight of 3 kg in recent 1 month. He had been previously admitted to the hospital for active tuberculosis 5 years ago and finally recovered completely. No history of diabetes, coronary artery diseases, hypertension, hepatitis, drug allergy, previous trauma, or operation was demonstrated. Laboratory tests revealed the following: red blood cell (RBC) count, 4.18 × 1012/L (normal range, 3.68–5.13 × 1012/L); hemoglobin concentration, 137 g/L (normal range, 114–151 g/L); white blood cell (WBC) count, 11.5 × 109/L (normal range, 4–10 × 1012/L); platelet count, 289 × 109/L (normal range, 100–300 × 109/L). Tumor markers were detected as the following: α-fetoprotein (AFP), 3.60 ng/mL (normal range, 0–15 ng/mL); carcinoembryonic antigen (CEA), 1.26 ng/mL (normal range, 0–5 ng/mL); carcinoma antigen (CA) 19-9, 5.6 U/mL (normal range, 50.1–27 U/mL). A chest x-ray showed bilaterally patchy infiltrates, increased bronchovascular markings and mass in the right lower lung fields (Fig. A), which needed further computerized tomography (CT) detection suggested by radiologists. A plain x-ray of the abdomen showed the gaseous distention of the bowel with air-fluid levels (Fig. B). Abdominal gaseous echoes were detected by ultrasonography. CT scans of the chest showed bilateral upper-lobe with patchy infiltrates, focal calcification and nodular opacities peripherally with cavitation, which indicated the changes of post-primary pulmonary tuberculosis (Fig. A); CT scans of the abdomen showed air-fluid levels in loops of small bowel, which indicated that mechanical obstruction was a likely diagnosis (Fig. B). Pathologic consultation of gastroscopic biopsy specimens in our hospital confirmed the diagnosis of squamous-cell carcinoma. Given the rarity of gastric squamous-cell carcinoma, pathologists suggested that further examination was needed to find the primary tumor. An enhanced CT scan was performed in this condition and the results were shown that the enhancement of right lower lung fields was not evident, which implied lung sclerosis after tuberculosis (Fig. ).
On March 5, 2014, the suddenly occurred abdominal pain was persistent and severe. The diagnosis of acute abdomen was made and urgent surgery was needed. The patient underwent a laparotomy with curative gastrectomy for gastric cancer and small bowel partial resection. Intraoperatively, a mass with a diameter of 0.8 cm was palpable in the greater curvature of the stomach and there was no significant lymphadenopathy (Fig. A, B). In addition, a mass with a diameter of 3 cm was found in the small bowel at the distance of approximately 30 cm to ileocecal area and the bowel became completely obstructed (Fig. C, D). Postoperative histopathology confirmed a moderately-differentiated squamous-cell carcinoma with full-thickness infiltration and vessel invasion in stomach (Fig. A, B) and small bowl (Fig. C, D). The margins of resection were free of tumor in the specimens and no regional lymph node metastasis was found in perigastric and perienteric area. In view of the rareness of gastrointestinal multiple primary squamous-cell carcinoma, further research was recommended by pathologists to exclude the metastatic squamous-cell carcinoma from the lung or the esophagus.
Esophageal mass or lesion was not found on endoscopic examination and the metastatic squamous-cell carcinoma from the esophagus was excluded. It was important to attempt to isolate the tumor cells from the sputum and to carry out a lung biopsy. In the fifth examination of stained smears of sputum, squamous-cells with properties of tumor cells were found. Meanwhile, transbronchial aspirates were obtained with a 19-gauge flexible histology needle by using a CT scan as a guide and squamous-cell lung cancer was confirmed (Fig. A, B).
The diagnosis of lung squamous-cell carcinoma with multiple metastases to the stomach and small bowl was confirmed. As the tumor was not resectable, surgeons recommended conservative treatments. The patient was recommended with combination chemotherapy of carboplatin and paclitaxel for 3 cycles. However, in September 2014, the patient succumbed to respiratory failure. |
pmc-6023843-1 | A 96-year-old woman was admitted to our hospital due to a 7-day history of fever over 39°C and 2 episodes of vomiting. By the time of admission, she had had abdominal pain, nausea, and lack of appetite for over a month. The family called an emergency ambulance but twice did not allow the patient to be taken to hospital. Because of her deteriorating condition, which was showing no improvement with oral amoxicillin with clavulanic acid 3 times a day (0.625 g), she was referred to our department to improve her poor condition. She had undergone appendectomy in her forties and hip bone fracture in 2013. She had not been administered any drugs so far.
Clinical examination revealed full mental conscious, dehydration, pulse rate of 90 beats/min, blood pressure 120/70 mm Hg, a body temperature of 39.5°C, left-side alignment of the alveolar murmur at the base of the left lung, local tenderness in the right upper abdomen without muscular defense. Her initial laboratory measurements showed a white blood cell (WBC) count of 17.77 × 109/L (norm: 4 × 109–10 × 109/L), with 86.8% neutrophils, hemoglobin at 6.80 mmol/L (norm: 7.45–10.00 mmol/L), erythrocyte sedimentation rate (ESR) was 86 mm (norm: 3–15 mm), and C-reactive protein level was 177.00 mg/L (norm: 0.00–5.00 mg/L). AUS showed gallbladder enlargement with stones and widening of the common bile duct (CBD) to 16 mm. The patient was consulted by the surgeon who, due to the high risk of mortality, decided to carry out intravenous antimicrobial therapy with ciprofloxacin 2 times a day with a dose of 0.4 g, metronidazole 2 times a day with a dose of 0.5 g, intravenous rehydration and alimentation, and spasmolytic drugs. We observed a mild improvement in the patient's condition with a decrease of body temperature to 36.8°C. Unexpectedly, 10 days after admission, we observed aggravation of the abdominal pain and fever recurrence up to 39.9°C, with an increase in serum and urine amylase to 257 U/L (norm: 25–115 U/L) and 418 U/L (norm: 30–200 U/L), respectively. CT of the abdomen revealed gallbladder stones with a widening of the CBD to 13 mm and widening of the Virsung duct to 8 mm, as well as some small pancreatic cysts with a pancreas tumor of 38 mm in diameter. CT also revealed aneurysm of the abdominal aorta, left suprarenal tumor, and esophagus hernia that had not been previously diagnosed. Abdominal MRI confirmed calculous cholecystitis and pancreatitis, probably with inflammatory tumor of the pancreas. After multidisciplinary consultation, we decided to treat the patient with meropenem intravenously three times a day at a dose of 1.0 g. The patient did not consent to undergo surgery. Over the next few days, the patient's health significantly improved, and after three weeks of hospitalization she was discharged home, with neither fever nor abdominal pain. She received restricted dietary recommendations. After discharge, the patient further gradually regained her physical health and returned to the condition she had presented before the disease. Four months after hospitalization, her laboratory tests showed a WBC count of 6.09 × 109/L, with 72.5% neutrophils, hemoglobin at 7.70 mmol/L, ESR of 38 mm, and C-reactive protein level at 1.03 mg/L. The patient was administrated pancreatic enzymes twice a day at a dose of 10,000 units before meals. Her blood pressure was well-controlled and she has had no recurrence of the fever or abdominal pain. |
pmc-6023852-1 | A 17-year-old woman, gravida 1, para 0, came to our hospital in labor at 36 weeks of gestation for care at birth. Case history revealed that she had not attended any check-ups during her pregnancy. The physical examination showed a 60% to 70% effaced and 3-cm dilated cervix, the fetus had cephalic presentation, and amniotic membranes were intact. Fetal ultrasound showed an isolated anechoic hepatic cyst measuring 1.32/1.47 cm. The cyst was situated in the right anterior abdominal compartment between the gallbladder and the umbilical vein, and at that time it was not certain if the cyst was located in parenchyma or choledocal. Because of the position of the cyst, close to fetal abdominal wall, we suspected that it was a parenchymal cyst (Fig. ).
Color Doppler flow imaging did not show any flow in the cystic mass and showed that it was situated to the right of the umbilical vein (Fig. ).
A female fetus was vaginally delivered in cephalic presentation shortly after her mother was admitted. The weight at birth was 2440 g, and the newborn was diagnosed with low weight for gestational age. The Apgar score value was 8 at 1 minute and 10 at 5 minutes. Unremarkable acid/base, co-oximetry, oxygen status, and electrolytes values from umbilical arterial blood were documented immediately after birth.
At 36 hours after birth the hepatic function panel showed a slightly elevated aspartate aminotransferase level of 43 U/L, slightly greater than the upper limit of normal (37 U/L). The total bilirubin level was of 5.2 mg/dL, corresponding to the low-risk zone at 36 hours after birth, according to the Bhutani nomogram.
The newborn was referred to the pediatric surgery unit, for further multidisciplinary evaluation. The evaluation by abdominal sonography confirmed the presence of a 1.6/0.93 cm intrahepatic cyst situated to the left of the gall bladder, without communication with the gall bladder or the common bile duct. The multidisciplinary team recommended periodic ultrasound monitoring of the cyst (Figs. and ).
The baby was reevaluated at 18 months after birth. Laboratory evaluation showed normalization of hepatic function panel and sonography showed complete resolution of the hepatic cyst (Fig. ). |
pmc-6023877-1 | A 58-year-old woman with a 2-year history of polyarthropathy had a diagnosis of RA (Fig. ). She was treated with oral corticosteroids (15 mg/QD), methotrexate (MTX) 10 mg weekly, and/or a nonsteroidal antiinflammatory drug. Her steady situation lasted for 16 months. In the recent 8 months, she experienced severely impairing and dizzines s and anemia. The blood test revealed normocytic anemia and she was admitted to the local hospital. Laboratory results were as follows: white blood cell (WBC) count, 5.48 × 109 cells/L; hemoglobin (Hb) count, 34 g/L; erythrocyte mean corpuscular volume (MCV), 89.0 fl, platelet (PLT) count, 381 × 109 cells/L; erythrocyte sedimentation rate (ESR), 138 mm/h; CRP, 117 mg/L; rheumatoid factor, 223 IU/mL; anti-cyclic peptide containing citrulline, 885.6 RU/mL; anti-nuclear antibody/anti-phospholipid antibodies/anti-neutrophil cytoplasmic antibodies, negative; vitamin B12, 368 pmol/L; folic acid, 4.6 nmol/L; erythropoietin, normal; serum ferritin, 287.96 ng/mL. At this point, MTX was discontinued and the patient received red blood cell transfusions. After treatment with glucocorticoids (methylprednisolone 4 mg/TID for 12 weeks), joint symptoms and CRP/ESR improved. However, the patient's hemoglobin level declined to 32 g/L. Even though folic acid tablets and ferrous sulfate were also administered, the response remained poor. The patient was referred to our hospital. Re-examination was conducted after red blood cell transfusion with the following laboratory data: WBC, 2.3 × 109 cells/L; Hb, 49 g/L; PLT, 237 × 109 cells/L; ESR, 108 mm/h; CRP, 61 mg/L; ferritin, 2325 g/L; and IL-6, 214.24 pg/mL.
The examination of bone marrow aspiration demonstrated dysplastic features on 2 hematopoietic lineages, but more prominent in the erythroid, which showed clustering with nuclear budding, pedal nuclei, and H-J bodies (dysplasis >10%). The double nuclei and megaloblastic changes could also be observed in the granulocytic lineage (accounting for 4%). The number of megakaryocytes was increased and the production of thrombocytes was fine (Fig. ). In addition, bone marrow biopsy also revealed hypercellularity and erythroid hyperplasia. Cytogenetic analysis showed a normal 46 XX [20] karyotype.
Combining her medical history with the clinical and laboratory parameters, a diagnosis of treatment-related MDS (t-MDS) was made. Disease modifying antirheumatic drug (MTX) might have been responsible for the bone marrow toxicity.
These results, in combination with the patient's history, led to the addition of tocilizumab to the treatment regimen. To evaluate the clinical effects of tocilizumab in the RA patient, WBC, Hb, ferritin, ESR/CRP, and IL-6 were assessed at baseline, 1st, 3rd, and 6th months of tocilizumab treatment. She started therapy with intravenous injection of tocilizumab (8 mg/kg) every 4 weeks and oral corticosteroids (15 mg/QD), achieving clinical benefit and improvement in symptoms. One month after admission, the patient was discharged from hospital. Laboratory results at that time were: WBC, 8.6 × 109 cells/L; Hb, 97 g/L; CRP, 7.2 mg/L; ESR, 26 mm/h; ferritin, 936 g/L; and IL-6, 23.85 pg/mL. Upon hospital admission, 2 months after the regular checkup, the results were: WBC, 6.9 × 109 cells/L; Hb, 73 g/L; CRP, 41 mg/L; ESR, 38 mm/h; ferritin, 231 g/L; and IL-6, 1.12 pg/mL. Repeat bone marrow aspiration at the 6-month follow-up showed that dysplasia was not obvious. Laboratory results showed no obvious abnormality. This resulted in the prompt resolution of the patient's serological, physical, and pathological abnormalities. Hence, the response to tocilizumab treatment was very good.
However, it was shown to be unlikely that the use of low doses of steroids in the patient was responsible for the sustained disease control. The patient refused the injection of tocilizumab after the 6th month. CRP (92.6 mg/L) increased and joint pain returned. Despite this relapse, the patient's laboratory examination was stable and symptoms significantly improved after resuming treatment with tocilizumab (Fig. ). |
pmc-6024047-1 | A 20-year-old male patient was admitted to our hospital with abdominal pain in the epigastric region, weight loss, and fever for 2 months. He had low back pain for 6 months and was evaluated for this complaint in another hospital. He had significant weight loss of 10 kg in 2 months and fever especially at nights. Past or family history revealed no signs of chronic or significant illnesses. Physical examination was normal. X-ray chest was normal. Anteroposterior plain radiograph of the sacroiliac joints revealed grade II bilateral sacroiliitis. Human leukocyte antigen B27 was positive. Liver and kidney function tests were normal. Lactic acid dehydrogenase was 229 U/L, upper of normal limits. Hemoglobin was 9.6 gm/dL; the patient had iron deficiency anemia. Serum angiotensin-converting enzyme level was 10.7 U/L (normal 8.0-52). His human immunodeficiency virus status was negative. F-18 FDG PET/ CT revealed multiple hypermetabolic malignant lymphadenopathies at gastrohepatic, gastrosplenic, celiac, superior mesenteric, peripancreatic and hepatobiliary region, and paragastric region in size as 18 × 15 mm (SUVmax: 12.3) and diffuse gastric wall thickening as linitis plastica (SUVmax: 13.3), multiple hypermetabolic peritoneal implants in the omentum (SUVmax: 5.7) and peritoneum, and mild hypermetabolic suspected malignant lymph nodes at left supraclavicular region (). Gastric ulcer at incisura angularis was detected on upper GI endoscopy (). Endoscopic biopsies were repeated for histopathological and microbiological differential diagnosis. Histopathological examination showed granulomatous gastritis, Langhans-type giant cells, granulomas composed of epithelioid histiocytes, ulceration, and exudates in the two samples. Real-time TB-PCR were negative, Erlich-Ziehl-Neelsen staining bacteria were negative. Gastric fluid examination revealed Gram-positive cocci, Gram-positive bacillus, and no leukocytes. Exploratory laparotomy was done to sample the biggest sized lymph nodes for tissue diagnosis and explore the peritoneum for TB infection, lymphoma, and Crohn’s disease to make differential diagnosis. During laparotomy, the abdomen and peritoneum were intact and normal; two lymph nodes were extracted for histopathological and microbiologic diagnosis. Histopathology of the lymph nodes extracted by exploratory laparotomy revealed granulamatous lymphadenitis with granulomas including giant cells, mostly suspecting TB (). Ankylosing spondylitis was also diagnosed. Bath ankylosing spondylitis disease activity index score was 1.0, disease activity was low. Patient was put on ATT consisting of (2HREZ/7HR) regimen as isoniazid, rifampicin, ethambutol, and pyrazinamide at therapeutic doses for initial 2 months followed by rifampicin and isoniazide in the same doses for the last 7 months. At the 6th week of treatment, he gained weight about 6 kg and he was feeling healthy. Hemoglobin was 12.6 gm/dL. We performed follow-up F-18 FDG PET/ CT. The F-18 FDG PET/ CT images (maximum intensity projection, CT, and fusion PET/ CT) exhibited a complete response to ATT with no residual disease ().
We have taken written informed consent from the patient reported in this study. |
pmc-6024051-1 | An 11-year-old thin-built, anemic girl was brought to the emergency with complaint of pain in upper abdomen and recurrent vomiting since 1 week. Abdominal examination revealed a nontender lump in the epigastric region, which was moving with respiration. Rest examination was normal. In laboratory examination, microcytic hypochromic anemia was seen; other parameters were normal. Parents gave history of disturbed behavior of child for past few months and decreased appetite. Sibling of the patient had seen her chewing her hairs infrequently, but did not think of it to be a major problem.
She was initially admitted in other hospitals for this, where conservative management was given, but there was no relief. Along with other routine investigations, UGIE was done in which there was a large blackish mass in the stomach and the sample taken from it showed mostly hairs. Based on the history and examination, diagnosis of trichobezoar was made and patient was taken for surgery. Anterior gastrotomy was done () and large hair ball mass () which was occupying the whole stomach and extending into duodenum was removed. Postoperative period was uneventful and she was discharged after psychiatric consultation. After 6 months follow-up, patient is doing well. |
pmc-6024069-1 | This is not a clinical study. Therefore, ethic approval is not needed. Father of the patient provided the written informed consent.
A 19-year-old man presented with polydipsia and polyuria with muscle weakness for more than 1 month. His urine output was approximately 4 to 7 L/d. He later developed vomiting and paralysis. He was admitted to a local hospital and was hospitalized with severe hypokalemia (1.9 mmol/L) and metabolic acidosis (pH 7.22, pCO2 26.0 mm Hg, HCO3 10.6 mmol/L, lactate 7.1 mmol/L, base excess −15.6 mmol/L). The patient recovered from paralysis on the third hospital day with serum potassium level 3.1 mmol/L and normal blood gas results after appropriate therapy. He presented to our hospital for further evaluation. Physical examination was only significant for pallor. He did not have a family or personal history of neuromuscular, thyroid, or autoimmune disease.
At the time of admission, laboratory evaluation revealed the following abnormalities: white blood count 3.16 × 109/L, hemoglobin 74 g/L, and platelet count 128 × 109/L. Serum chemistry showed: sodium 140 mmol/L, chloride 108 mmol/L, potassium 3.18 mmol/L, calcium 1.89 mmol/L, creatinine 57.8 mmol/L, and bicarbonate 19 mmol/L. Urinary pH was 6.5, with sodium 80 mmol/L and potassium 18.68 mmol/L; chloride, calcium, and creatinine were normal. A 24-hour urine test started on the day of admission revealed the following: sodium 320 mmol/24 h, potassium 74.7 mmol/24 h, calcium 12.24 mmol/24 h, and protein 988.00 mg/24 h. Serum and urinary osmolality were 303 and 158 mOsm/kg, respectively. Growth hormone, insulin-like growth factor 1, thyroid hormone, adrenocorticotropic hormone, plasma aldosterone, renin activity, antinuclear antibody, and anti-Smith antibody were within reference range. Other chemistries and coagulation parameters were in normal range.
Brain magnetic resonance imaging showed an abnormal pituitary gland, and he had an insignificant response to a water deprivation test after vasopressin injection. The findings suggested NDI. With overt acidosis (plasma bicarbonate <20 mmol/L) and urinary pH > 6.0, we confirmed the coexistence of renal tubular acidosis. Abdominal ultrasonography revealed symmetrical homogeneous kidneys with hyperechogenic pattern and poor corticomedullary differentiation (Fig. ). Because of the hematologic abnormalities, bone marrow aspiration was performed and revealed 39% blast cells. The immunophenotypic analysis showed blast cells positive for CD34+, CD38+, CD10+, CD19+, CD22+, cyCD22+, CD79+, HLA-DR+, and TdT+. Cytogenetics showed normal male karyotype. Cerebrospinal cytology was negative. He was diagnosed with precursor B-cell ALL with acquired NDI. Leukemic infiltration of the kidneys may have led to polydipsia and polyuria.
This patient had an excellent response to standardized combination chemotherapy and achieved complete remission (CR) at the end of induction. His polydipsia and polyuria improved considerably after 3 days of chemotherapy. He refused the best therapy of allogeneic stem-cell transplantation (allo-HSCT) at that time. Unfortunately, leukemia relapsed after sustained remission for 1 year. As a human leukocyte antigen-matched related or appropriate unrelated donor was not available, haplo-SCT was an alternative. He received haplo-SCT from his father after a second CR. Unfortunately, 20% blast cells were found in bone marrow 6 months after haplo-SCT. Next, a graft-versus-leukemia effect was successfully induced with the intervention of donor lymphocyte infusion, which achieved sustained remission. At 1 year after haplo-SCT, the patient developed a fungal pulmonary infection and was found to have bilateral renal enlargement with low density on abdominal computed tomography (Fig. ). Abdominal ultrasonography revealed symmetrical homogeneous kidneys with a hyperechogenic pattern and poor corticomedullary differentiation. The left kidney measured 17.1 cm × 9.6 cm, and the right kidney measured 16.9 cm × 9.7 cm. He returned 9 days later with muscle weakness, paralysis, polydipsia, and polyuria. Finally, he died of NDI and subsequent medullary relapse. |
pmc-6024093-1 | A 15-month-old girl was admitted to the Peking Union Medical College Hospital (PUMCH). The girl had experienced high fever for 3 weeks, irritability for 2 weeks, and refusal to walk for 1 week. Three weeks before admission to PUMCH, she was seen at a local clinic (Haikou City, Hainan Island, located in the southern end of China) for fever and constipation. Physical examination was normal, and she was treated with ibuprofen. One week later, she presented to Haikou People's Hospital with a persistent high fever of over 39.5°C, irritability, and crying during the night. The result of head computer tomography scan was normal, and lumbar puncture revealed an opening pressure of 140 mm H2O. Her cerebrospinal fluid (CSF) was clear and had 120 × 106/L white blood cells with 38% neutrophils and 62% lymphocytes. The patient was treated for viral meningitis with an antiviral for 2 weeks. Thereafter, she refused to walk because of lower limb pain. The patient's fever was not relieved by treatment.
This girl was gravida 1 para 1 and was the full-term baby of an uncomplicated pregnancy. She had been raised in the countryside of Hainan Island. She had normal developmental milestones, uneventful previous history, and full immunization for her age.
The patient cried and was extremely irritable during the physical examination. The physical examination showed that she had a weight of 11.5 kg and a temperature of 40°C. Rashes, lymphadenectasis, and joint redness were not observed. Skin sensation could not be evaluated because the patient responded to any skin contact with exaggeration and crying. The patient's muscle strength and tone were normal even though she refused to stand or walk. The jerk reflexes of her limbs were symmetrical, and her pathological reflex was negative. No obvious focal neurologic signs were detected.
Laboratory tests showed a peripheral blood leukocyte count of 12.6 × 109/L with an increased eosinophil count of 21.3% and absolute eosinophil count of 2.69 × 109/L. The results of renal and liver function tests and routine urine and stool tests were normal. Serum IgM antibodies to cytomegalovirus, herpes virus simplex, and Epstein-Barr virus were negative.
The magnetic resonance image of her brain was normal. Lumbar puncture disclosed an opening pressure of 200 mm H2O, and the CSF appeared cloudy. CSF cytology showed a white blood cell count of 400 × 106/L with 70% eosinophils, 32% monocytes, and 3% lymphocytes (Fig. ). The chemistry test results of the patient's CSF showed 2.2 mmol/L glucose, 122 mmol/L chloride, and 600 mg/dL total protein. The Gram stain, India ink stain, and the acid-fast stain results of the CSF were negative. CSF aerobic and anaerobic cultures and cultures for Mycobacterium tuberculosis and fungi were all negative.
Parasitic eosinophilic meningitis was highly suspected because of the patient's increased blood and CSF eosinophil count and persistent neurological symptoms. The mother was further questioned for the infant's exposure history. She recalled seeing the child play with slugs.
Eosinophilic meningitis was diagnosed clinically on the basis of the child's exposure history, and parasite-specific investigations were initiated. The suspected third-stage larvae of A cantonensis were found in the CSF. However, a reference laboratory in Beijing Tropical Medical Research Center reported that the patient's serum sample tested negative for antibodies against A cantonensis.
Considering the patient's clinical symptoms and signs, increased intracranial pressure and eosinophil levels in peripheral and CSF samples, and lack of response to antiviral treatment, as well as the presence of parasites in CSF, oral empiric treatment with 2.5 mg/(kg/day) levamisole and 1.5 mg/(kg/day) prednisone together with mannose was initiated to reduce intracranial pressure.
The patient exhibited rapid recovery, and all of her symptoms resolved approximately 72 hours after the commencement of treatment. Hematological testing and CSF examination revealed that the child's eosinophil count had decreased. Thus, prednisone dosage was gradually decreased. Another lumbar puncture performed 4 weeks after the first lumbar puncture revealed that the eosinophil levels in the child's CSF had decreased to 0. The patient was discharged from the hospital and completed 4 weeks of treatment with levamisole and prednisolone. At the 6-month follow-up, the patient showed normal growth and development without sequelae. |
pmc-6024161-1 | A 10-year-old girl presented with a 2-day history of constant right-sided flank pain with intermittent episodes of increased intensity. Movement and laying supine exacerbated the pain, whereas some relief was found with paracetamol. There was no trauma to the area, but the patient reported playing netball shortly before the pain started. There was no associated nausea, vomiting, or change in bowel or urinary habit. There was no fever and no symptoms of cough or breathing difficulties.
The patient had no significant medical history and immunisations were up to date. On examination, she was apyrexial with a heart rate of 110 beats per minute, oxygen saturations of 99% on room air and respiratory rate of 22 breaths per minute. She was warm and well perfused with a central capillary refill time of <2 seconds. She appeared distressed when laying down reporting worsening pain; however, the abdomen was soft and non-tender to palpation. Systemic examination was otherwise unremarkable.
Urine analysis showed no evidence of infection and blood tests revealed a C-reactive protein (CRP) of 23 mg/L and a normal full blood count with white cells of 13.4 × 109 cells/L. Liver function tests, urea and electrolytes, and venous blood gas were also normal.
With normal observations, examination and investigation results and a good response to analgesia in the department, the patient was discharged with a planned review.
On re-assessment the following day, she continued to complain of significant pain on the right side of the abdomen with similar features on examination. Owing to the persistence of symptoms, chest radiography (Fig. ) and abdominal ultrasound were performed. Both were reported as normal. With no surgical or medical cause of the pain identified, it was deemed musculoskeletal in origin, associated with playing netball. She was discharged with advice to take regular analgesia and to return if symptoms were not settling.
The patient represented the following day looking unwell. She appeared very pale with dry lips and walked slowly, hunched over. She was tachycardic at 130 beats per minute and tachypnoeic with a respiratory rate of 32 breaths per minute. Oxygen saturations, temperature, and blood pressure were normal at 98%, 36.80C, and 119/72 mmHg respectively. She stood with her right hip and knee slightly flexed, with her trunk deviated to the left giving her a marked scoliosis. Musculoskeletal examination of the spine, hips, and knees was unremarkable, but it was noted that abdominal pain worsened on flexion of the hip against resistance. Cardiovascular and respiratory examinations were normal. She was unable to lie supine because of severe pain and was examined in the semirecumbent position. Active distension of the abdomen and coughing further exacerbated the pain and she was found to have guarding with rebound tenderness in the right flank and hypochondrium. An intravenous cannula was inserted and intravenous fluids, paracetamol, and ibuprofen were commenced while awaiting a surgical review for her acute abdomen. Concurrent orthopedic opinion was also sought because of the new-onset scoliosis.
After treatment the patients’ pain was significantly reduced, pallor had resolved and her observations normalised. Abdominal examination at the time of surgical review was normal, but because of repeated presentations with abdominal pain and a rising CRP (93 mg/L) and white cell count (13.9 × 109 cells/L) the patient was admitted and a computed tomography (CT) scan of the abdomen and pelvis was arranged. Orthopedic review did not yield any acute orthopedic concerns regarding the scoliosis and they agreed with the plan for abdominal imaging. The CT scan failed to reveal an abdominal cause for her pain, but to our surprise showed an organizing right lower lobe pneumonia with a small effusion (Figs. and ).
The patient was started on intravenous antibiotics for the thus far silent pneumonia. Despite treatment during the next few days, the pneumonia progressed and she developed a large parapneumonic effusion (Figs. and ). On the 6th day of hospital admission, she deteriorated rapidly with signs of sepsis and respiratory distress. This was accompanied by a further rise in CRP (351 mg/L) and white cell count (17.3 × 109 cells/L). She was stabilized and then transferred to a tertiary hospital for further management.
At the tertiary center, a chest drain was inserted and the patient was treated with intrapleural urokinase therapy and intravenous antibiotics. She was discharged after a 2-week stay.
With the complete resolution of the pneumonia and scoliosis, the patient made a graduated return to school and at 4 months post discharge was almost back to full-time attendance. |
pmc-6024479-1 | A 41-year-old female patient was admitted to the Department of Respiratory Medicine due to hemoptysis. The patient had first experienced hemoptysis with a small amount of fresh blood and neutral-smelling yellow sputum 10 years previously. She denied breathing difficulties and chest pain. Chest computed tomography (CT) scans met the diagnostic criteria for bronchiectasis[ combined with infection (Fig. ). The patient's condition improved after administration of intravenous antibiotics (ceftriaxone and clarithromycin) and intravenous hemostasis (hemocoagulase) treatment. The patient then experienced disease recurrence once or twice per year and was again diagnosed with bronchiectasis combined with infection each time. After treatment with anti-inflammatory and hemostatic therapy, the patient's condition also improved each time. Seven days prior to presentation in our department, the patient began to cough with a small amount of yellow sputum and dark red blood. The same treatment strategy was again given in the local hospital, but the patient's symptoms were not improved. One hour prior to presentation in our department, the patient's symptoms became aggravated with increased hemoptysis of about 100 mL fresh blood combined with chest pain and difficulty breathing.
Laboratory tests showed a white blood cell count of 13.5 × 109/L, neutrophil percentage of 76%, lymphocyte percentage of 17%, neutrophil count of 10.33 × 109/L, and monocyte count of 0.8 × 109/L. The test for tuberculin was negative. Blood gas analysis revealed an oxygen concentration of 33%, pH of 7.36, PCO2 of 44 mmHg, PO2 of 60 mmHg, HCO3− of 24.9 mmol/L, and base excess of –0.8 mmol/L. Tests of coagulation time, liver function, and kidney function showed no abnormalities. Chest CT showed increased patchy high-density shadows in the left lower lobe of the lung with visible bronchial broadening as changes to the patient's “bronchiectasis” (Fig. ).
The patient received a 7-day course of intravenous antibiotics (moxifloxacin) and hemostasis therapy (hemocoagulase/ethylenediamine diaceturate injection) as empiric therapy after admission. The patient's symptoms improved with reductions in coughing, sputum discharge, and hemoptysis involving mostly old clotted blood only. Then, enhanced chest CT showed an increased texture of the 2 lungs, widening of the bronchus of the lower portion of the left lower lobe, thickening of the adjacent left lower pulmonary veins and arteries, enhancement of the arterial phase of enhancement, reduction of venous phase enhancement, an increase in the patchy blur density around the trachea, and the trachea. The opening of the main bronchus was unobstructed. Lymph nodes were not seen in the mediastinum, and no obvious effusion was seen in the chest. A left lower lobe lobectomy was performed, and the postoperative pathology revealed a hemangioma of the left lower lobe of the lung without bronchiectasis (Fig. ). Three months later, the patient had no hemoptysis, sputum, or dyspnea. Lung CT showed only the expected postoperative change and no abnormal shadows or bronchiectasis. |
pmc-6024491-1 | A 44-year-old woman presented to the emergency department with complaint of intractable nausea and vomiting associated with severe epigastric pain of 2 days duration. She denied any changes in her bowel habits. Review of systems was otherwise negative. She is status post sleeve gastrectomy 2 years prior and had a history of a remote laparoscopic cholecystectomy. Physical examination was only notable for mild epigastric tenderness. Laboratory tests showed aspartate aminotransferase 46 IU/L, alanine aminotransferase 65 IU/L, alkaline phosphatase 75 IU/L, and otherwise normal including lipase. A right upper quadrant ultrasound showed dilation of the common bile duct, which was again demonstrated on magnetic resonance cholangiopancreatography as well as a 7-mm common bile duct stone. The patient subsequently underwent ERCP with sphincterotomy. Cholangiogram at the time demonstrated a dilated common bile duct with no obvious cause. A few hours postoperatively, the patient started experiencing severe epigastric and left upper quadrant abdominal pain radiating to the back. She was found to be hypotensive and immediate fluid resuscitation was initiated. Repeat laboratory testing at the time showed a lipase of 1300 IU/L as well as a decline in hemoglobin from baseline of 12.0 g/dL to 7.0 g/dL. A CT (computed tomography) scan of the abdomen illustrated a large splenic heterogeneous subcapsular hematoma and peripancreatic stranding ( and ). The patient was transferred to the intensive care unit and managed conservatively with fluids and blood transfusions. The hematoma regressed, and her hemoglobin remained stable. With clinical improvement, she was discharged home. |
pmc-6024592-1 | A 25-year-old male, right hand dominant and manual labourer by occupation came to our hospital with history of pain and stiffness of right elbow for last 2 years. Pain was mainly worse after periods of rest and after waking up in the morning, with no history of nocturnal exacerbations. Pain relived only partially with salicylates and other non-steroidal anti-inflammatory medications. He had no other musculoskeletal complaints or any other significant past medical history. He had previously sought consultation in other places and various diagnoses such as lateral epicondylitis, mono-articular rheumatoid involvement.
Physical examination revealed no swelling or fullness around the elbow. There was mild tenderness along the anterior aspect of elbow. There was restriction of both flexion and extension with elbow range of motion from 30 to 90°. Supination and pronation were normal. Plain radiographs were normal. Computed tomography (CT) with 3D reconstruction revealed a radio-dense ring measuring about 4 mm in the coronoid fossa of humerus. It had a radiolucent nidus measuring about 2 mm in diameter. There was a thin bony shell in the anterior aspect of the lesion. These findings were consistent with a diagnosis of a sub-periosteal osteoid osteoma. A decision of arthroscopic excision was made .
Elbow arthroscopy was carried out under general anesthesia in lateral decubitus position. Standard proximal anteromedial viewing (anterior and 2 cm proximal to medial epicondyle) and proximal anterolateral instrumentation portals (anterior and 2 cm proximal to lateral epicondyle) were used for elbow arthroscopy. A 2.7-mm, 30° arthroscope was used. The lesion was localised in the coronoid fossa. It appeared as a hyperaemic bony protuberance covered with hypertrophied synovium. Synovium was shaved with an arthroscopic shaver. Thin cortical shell over the lesion was removed with an arthroscopic shaver. The nidus was exposed and it shelled out easily upon manipulation with a curette. It was delivered through the anteromedial arthroscopic portal and sent for histopathology. The base of the lesion was cleaned with curette and burr. Normal bone deeper to the base of the lesion was not removed and posterior cortex was not perforated. No other arthroscopic releases were done. Intraoperative imaging was net required as the lesion was large and easily visible upon insertion of arthroscope.
Histopathology findings of the nidus were consistent with an osteoid osteoma. There was an interlacing network of osteoid and bony trabeculae with some mineralization. Histopathology of the synovium only showed features of non-specific chronic inflammation. Gram stain and culture results were negative. His complete blood counts, erythrocyte sedimentation rate and C-reactive protein were within normal limits.
Pain relief after the procedure was remarkable. He had no pain after 3 days and could resume his work. At latest follow up of 1 year patient is completely pain-free. He has full range of motion of the elbow (0–150°, ). |
pmc-6024813-1 | The first subject is a 25-year-old female with a history of obesity who had undergone RYGB 2 year earlier, at which time her BMI was 35.1 kg/m2. Two years after surgery, she started to experience frequent episodes of hypoglycemia with tachycardia, sweating, and neuroglycopenic symptoms including confusion, dizziness, and blurred vision. Such symptoms occurred both in the postprandial state and during the night and were so frequent to impact negatively on her working capacity and quality of life. On admission to our Clinic, the patient had lost 35 kg and her body weight was stable. Continuous Glucose Monitoring (CGM, Dexcom G4 PLATINUM) for seven days evidenced ample blood glucose excursions throughout the day, with glucose peaks above 200 mg/dL after meals, followed by a rapid fall below 55 mg/dL (a), which were associated with hypoglycemic symptoms as recorded in the patient’s diary. It is interesting to note that low glucose levels occurred also during the night, as demonstrated by the considerable time spent below 55 mg/dL. Based on the continuous glucose profile showing a clear postprandial pattern of hypoglycemia associated with symptoms, we posed the diagnosis of PBH. From CGM, we also calculated the main indexes of glucose variability; i.e., coefficient of variation (CV), standard deviation (SD), and mean amplitude of glycemic excursions (MAGE) that resulted in an increase, as reported in .
The patient was prescribed a normocaloric (1500 kcal) high-fiber (33 g), low-carbohydrate index (55) diet, which was divided into three meals and three snacks to avoid postprandial blood glucose peaks and prolonged fasting intervals (see ). Multivitamin and mineral supplements were also prescribed on the basis of biochemical analysis showing vitamin D (19 ng/mL) and iron (ferritin 10 ng/mL) deficiency.
Following nutritional therapy, the patient demonstrated a modest improvement of hypoglycemic symptoms but asthenia and tiredness in the early morning associated with fingerstick glucose level in the low range (<70 mg/dL) persisted. We supplemented the diet with a starting dose (30 g) of uncooked cornstarch administered before going to bed, which was progressively increased to 85 g/die (30 g in the morning and 55 g at bedtime; 1.25 g/kg b.w.) on the basis of the fingerstick home glucose profile. CGM, performed 12 weeks after beginning the cornstarch administration, showed a remarkable reduction in glucose variability indexes and postprandial glycemic peaks. Furthermore, the overall time spent in hypoglycemia (IG <55 mg/dL) decreased significantly. Of particular relevance is the reduction of the time spent in hypoglycemia during the night (from 23 to 1%; from 9.5 h to 35 min) (b). No side effect was recorded after cornstarch ingestion except for a slight abdominal distension during the first days of treatment. |
pmc-6024875-1 | A 50-year-old healthy female previously revealed the presence of a left renal mass by ultrasound 3 weeks ago. The patient had no significant back pain and gross hematuria. The abdominal contrast-enhanced CT demonstrated the presence of a mixed density mass with a size of 7.9 × 7.6 cm and clear boundary in the upper pole of left kidney (Fig. A). A slightly high- and low-density necrosis was found in the interior of the tumor, revealing an obvious uneven enhancement and the phenomenon of contrast agent fast forward and fast out (Fig. B and C). The left renal pelvis oppressed by the tumor was unclear. After the peritoneum, the nodular shadow was seen in retroperitoneal region, showing an obvious inhomogeneous enhancement (Fig. B and C). MRI revealed that the left kidney had an irregular contour. A mass of about 10.6 × 7.9 cm was observed in the upper left pole of the kidney. This was mixed with a short T1 signal, and showed an uneven internal signal. The vascular shadows and false envelop can be seen in the tumor. The enlarged lymph nodes were observed in the left renal hilum, with a diameter of about 2.3 cm (Fig. D and E). The patient under general anesthesia underwent radical resection of left renal carcinoma and renal hilar lymph node dissection through retroperitoneal route and resected the perirenal fascia, perirenal fat, kidney, ipsilateral adrenal, ureter above the iliac blood vessel bifurcation, and abdominal aorta and inferior vena cava lymph node from the angle of diaphragm to the bifurcation of the abdominal aorta. After incision of the kidney, a cut surface rotten bleeding of gray white tumor of 9 × 8 × 8 cm, and atrophied renal parenchyma were observed. Pathological examination revealed that the case was considered to be XP11.2 tanslocations/TFE3 gene fusions associated renal cell carcinoma with a size of 9× 8 × 8 cm, vascular region showed invasion of carcinoma, and left renal hilar lymph nodes were with metastases (2/2). PET-CT was performed, which revealed no other lymph nodes and organic metastases. So, the tumor observed was in T2N2M0 stage and IV stage according to AJCC Cancer staging Manual. Immunohistochemistry results revealed positive for CAIX, CD117, Ki67, Melan-A, TFE3 (+), AE1 / AE3 and CK8/18 (+), and negative for CD10, CK7, HMB, P504 s, Vimentin, EMA, PAX-8, and SMA. After operation, the patient was given sorafenib 400 mg bid. After 3 months follow-up, the patient was in good condition. |
pmc-6024875-2 | A 31-year-old female, who was not married, has been undergoing hemodialysis for more than 2 years without any obvious symptoms underwent CT for preparation of kidney transplantation. CT showed a solid cystic and low-density foci in the right kidney, and a nodular and slightly high-density shadow within the foci (Fig. A). The patient underwent radical resection of right renal carcinoma under general anesthesia. After the operation, the kidney was opened, and a white mass of 4 cm size and fine papilla on the surface of the lump in the right kidney was observed. Postoperative pathology revealed Xp11.2 translocations/TFE3 gene fusions associated with renal cell carcinoma with a size of 4∗3 cm. Immunohistochemical results showed positive for AE1/AE3, CD10, Vimentin, CD117, P504 s, Melan-A, and TFE3. The patient did not receive any other treatments. She was followed up for one month after operation, and showed no recurrence. |
pmc-6024875-3 | A45-year-old male, with a right lumbago for 1 month, underwent B mode ultrasonography. Results revealed a lower echo mass in the lower pole of the right kidney. The tumor was with a size of 5.4 × 4.8 cm, had a regular shape, but showed no clear boundary, and the internal echo was uneven. Then he was admitted in the hospital, and underwent middle abdomen plain and enhanced CT. Round tumor of 5.2 × 4.9 cm round tumor, with clear boundary and uneven density was observed (Fig. A). Laparoscopic radical nephrectomy was performed to open the right kidney. The right renal tumor with pigmentation had a clear tumor boundary. The tumor was considered as translocation of XP11.2 tumor associated with pigment differentiation, and had a low malignant biological behavior. Immunohistochemistry revealed positive for HMB45, Melan-A, S100, Ki67, and TFE3. After 3 months of operation, the patient showed no recurrence and did not undergo any other treatment. |
pmc-6025454-1 | This case describes a 21 months old, previously healthy boy, who presented with weakness of the lower extremities and lumbar pain after a mild upper respiratory tract infection. For this reason, he was immediately brought to the paediatric emergency department where he underwent a hip ultrasound that excluded a joint effusion. Nevertheless, he was dismissed with a diagnosis of transient hips arthritis and was treated with anti-inflammatory therapy. A few days later, because of worsening pain and the inability to walk, he returned to our department and was hospitalized.
On admission, a spine radiograph showed a slight reduction in the thickness of the L5 soma. Moreover, a spine magnetic resonance imaging (MRI) showed the T1 post-enhancement increased signals of the anulus L4–L5, of the opposite end-plates of L4 and L5, of the adjacent soft tissues and of the osteolytic area of the L5 pedicle. Therefore, a diagnosis of SD with associated osteomyelitis was made.
The blood exams revealed an increase in the inerythrocyte sedimentation rate (ESR) (77 mm/h,) and C reactive protein (CRP) (2.17 mg/dL, normal values < 0.4 mg/dL). In contrast, the patient had a normal white blood cell count (WBC) count, a normal procalcitonin serum concentration (0.12 ng/mL, normal values < 0.25 ng/mL), and a negative Quantiferon TB-gold test.
Broad-spectrum intravenous therapy with meropenem (100 mg/kg/day in three doses) and vancomycin (40 mg/kg/day in three doses) was started. Anti-inflammatory treatment was used for the first week and stopped with the complete resolution of the child’s symptoms and his return to normal walking.
After 3 weeks of therapy, the patient developed leukopenia with severe neutropenia (lowest WBC value of 5410/mm3, with 80/mm3 neutrophils). As both of the administered drugs have been associated with neutropenia [,], therapy was withdrawn and replaced with ceftazidime (100 mg/kg/day in three doses), which was carried on for another week until the second MRI. The images from this exam, performed after 4 weeks of total therapy, showed a reduction in the enhanced contrast, although there was not a complete resolution of the inflamed and infected state.
Because of the radiological improvement, the normalization of the inflammatory factors, and the absence of symptoms in the child, he was discharged with an oral therapy of linezolid (30 mg/kg/day in three doses) and cefuroxime axetil (30 mg/kg/day in two doses). After 12 weeks of oral therapy, another MRI was performed. The images showed a complete resolution of the infectious process. shows differences between the MRI at admission and during the follow-up. Therefore, therapy was stopped (the patient received 16 weeks of therapy in total). The child was completely asymptomatic, and all of the blood exams, including the acute phase reactants and blood culture, were in the normal range or negative.
All of the blood exams that were performed to determine the nature of the infection did not show positivity for any recent, causative infectious agent. Additionally, the immunological and autoimmunity screenings were normal.
The 3 year follow up did not reveal any problem after discharge. The child never felt additional pain or had problems walking again. |
pmc-6025454-2 | A 3 years old boy was admitted to our emergency department because he had been suffering from intermittent lumbar pain for several months and had difficulty walking for a few days. The patient’s personal medical history was uneventful until 4 months earlier when, playing with a friend, the child had a lumbar trauma that caused neither detectable skin lesions nor impairment to leg mobilization, and was not investigated. However, in the following weeks, the child started to feel pain whenever his father picked him up and was clearly more irritable than he had been in the past. A fever was never reported. Three months after the trauma, because of the increased lumbar pain, the child refused to walk. For this reason, he visited an emergency care unit and underwent a physical examination; laboratory blood tests, including a WBC and CRP serum level; and a full spine radiography. No abnormal results were detected. Oral therapy with a nonsteroidal anti-inflammatory drug for a week was prescribed. During this period, a partial resolution of the pain was demonstrated.
However, ten days after the drug discontinuation, the pain worsened. Therefore, the child was brought to our department. Here, a physical examination, an abdominal ultrasonography, and the laboratory blood tests were still normal or only slightly abnormal. The ESR reached 60 mm/h, CRP was 1.47 mg/dL (normal values < 0.4 mg/dL), and procalcitonin was 0.26 ng/mL (normal values < 0.25 ng/mL), but the patient had a normal WBC count. His body temperature was in the normal range. However, an MRI scan of the spine revealed that a T1 post-enhancement had increased the signal of the anulus L3–L4 of the adjacent soft tissue; this outcome is highly suggestive of an infective SD ().
While awaiting the results of the blood culture, a broad-spectrum, anti-infective intravenous therapy was started with piperacillin–tazobactam (100 mg/kg/day divided into three doses) and vancomycin (40 mg/kg/day divided into three doses). Oral anti-inflammatory therapy was also provided.
The boy experienced rapid clinical improvement. In the first weeks, he stopped feeling pain and started walking again without lameness. Anti-inflammatory therapy was discontinued after several days. After 4 weeks of therapy, the boy underwent a second MRI, which showed no significant radiological change (). The CRP was negative, but the ESR and procalcitonin were still slightly abnormal. The therapy was modified, and piperacillin-tazobactam was replaced by meropenem (100 mg/kg/day divided into three doses), while continuing vancomycin.
After 8 weeks of intravenous therapy, the inflammatory index was completely negative, and the child felt no more pain and could walk normally. The intravenous therapy was switched to oral therapy with linezolid (30 mg/kg/day in three doses) and cefuroxime axetil (30 mg/kg/day in two doses), and the child was discharged from the hospital.
After 12 weeks of total therapy, another MRI was performed to determine if therapy should be discontinued. The MRI showed an important reduction in the signal alterations, although residual irregularities of the end-plates of L3 and L4 were reported (). On the basis of these findings, the child remained on antibiotic therapy for another month and then stopped. He received 16 weeks of therapy in total.
During hospitalization, all of the immunological exams that were performed were normal, and no causative infectious agent was documented. The whole therapy was well-tolerated, without any side effects.
During a 3 year follow-up, the child experienced only one episode of back pain, for which he promptly underwent an MRI that ruled out the possibility of a reactivation of the infection, but he showed a slightly adipose evolution of the L3 and L4 body. After that episode, which rapidly and spontaneously resolved, the child never felt lumbar pain again and maintained a normal life. |
pmc-6025476-1 | An 11-year-old boy of Moroccan origin was admitted to the Pediatric Ward of the Perugia General Hospital in July 2016 because, in the last 15 days, he had suffered from mild fever, chills and night sweats, severe itching, continuous dry cough, and right temporal headache. Moreover, in the month before hospital admission, he had lost approximately 7 kg in weight. Finally, a previous evaluation of blood cell count had revealed HE (eosinophils 10,000/µL) without other significant alterations. The patient denied having recently taken drugs and had had contact with animals. His last trip to his country of origin was in December 2015.
On admission, a blood cell count and a morphological evaluation of a peripheral blood smear confirmed HE (white blood cells 21,950/µL, with eosinophils 13,762/µL, hemoglobin 11.9 g/dL, and platelets 237,000/µL) the absence of other cellular morphological abnormalities. In the following days, the patient presented fatigue and worsening of headache; therefore, attempts to evaluate HE and other signs and symptoms origin were made. A parasitological fecal examination and a Scotch tape test were performed on three samples with negative results. Organ infiltration was excluded through chest X-ray, brain magnetic resonance imaging, echocardiography, and abdominal ultrasound. Toxoplasma, Plasmodium falciparum, Leishmania, Schistosoma, Echinococcus, viral hepatitis, and HIV infection were also excluded. Results of tests regarding comprehensive metabolic panel, inflammatory markers, and autoantibodies were negative excluding autoimmune diseases.
A bone marrow aspiration was performed approximately 20 days after hospital admission. Morphological examination documented an increase in eosinophils without cellular morphological abnormalities, and bone marrow immunophenotyping showed that 4.5% of the cells had a phenotype compatible with lymphoid blasts. A lumbar puncture was negative. However, given the poor marrow involvement, it was necessary to repeat the bone marrow aspiration two days later; the results of the new aspiration showed an increase in blasts to 14% () with a normal immunophenotype on mature B ant T cells. Concomitant bone marrow biopsy showed a cellularity of 40% with an infiltration of blasts typical of B-cell ALL equal to 20–30% with marked associated hypereosinophilia.
Cytogenetic analysis showed a hyperdiploid karyotype: 53–55, XY, +X, add(1)(q21q25), +4, +9, +10, +14, +2, +1, +21/46, XY; FISH analysis confirmed the numeric and structural abnormalities revealed by karyotype, without cryptic additional events. In particular, no abnormalities were found on chromosome 5. The main molecular leukemic rearrangements—including BCR/ABL, MLL/AF4, TEL/AML1, and E2A/PBX1—were negative. The in vitro production of interleukin (IL)-5 by T CD4 + lymphocytes was increased (41%) compared to the negative control (11%).
A few days after the start of prednisone prophase, a marked drop in peripheral eosinophil count and rapid clinical improvement were evident. On day 78, the patient was assigned to the standard risk group of the AIEOP ALL 2009 protocol. The patient is now undergoing maintenance therapy (6 Mercaptopurin plus Methotrexate) and will stop it on August 2018. Until now, the patient remains in complete remission; no further increase of eosinophil count was demonstrated. |
pmc-6025697-1 | A 66-year-old woman presented with avascular necrosis in left hip, panniculitis, and later was found with diffuse systemic sclerosis and pulmonary fibrosis. She received low-dose methotrexate (15 mg/week) combined with prednisolone 5 mg b.i.d since 2014. Cyclophosphamide 50 mg twice daily was added in January 2015 and then further reduced to once daily in July 2016. The disease was well controlled with no further visceral organ involvement.
Two years later, she complained of gross hematuria and dysuria. She reported no fever, no suprapubic or flank pain, and no loss of appetite. Clinical examination revealed no abnormality except the diffuse skin thickening from her underlying disease. Urinalysis showed >100 red blood cells and leukocytes/μL, whereas urine culture was negative for organism. Her kidney function was within normal limit. Ultrasonography of the kidney, ureter, and bladder system revealed normal kidneys and turbid urine in the urinary bladder. No vesical mass or stone was detected.
Cystoscopy was done and showed a white-yellowish plaque in the bladder (). Hematoxylin and eosin stain (magnification: 400 × ) shows sheets of large macrophages with granular eosinophilic cytoplasm and mixed inflammatory cells infiltration (). Stain of von Kossa (400 × ) shows Michaelis–Gutmann bodies ().
The cyclophosphamide was permanently stopped, and she was treated with ciprofloxacin 500 mg orally twice daily for 2 weeks. She did not receive any intravenous antibiotics. She reported neither hematuria nor dysuria after full course of antibiotics and the urinalysis showed 5–10 leukocytes/μL and 1–2 red blood cells/μL. She continued the prophylactic dose of trimethoprim–sulfamethoxazole as well as prednisolone and methotrexate. |
pmc-6025712-1 | A 12-year-old girl presented to her general pediatrician complaining of asthenia and weight loss in the previous month. Her past medical and family history were unremarkable. Physical examination revealed a painless hepato-splenomegaly without additional clinical signs. Abdominal ultrasound revealed an inhomogeneous liver appearance, abdominal lymphadenopathy and a hypo-echogenic solid neoformation in front of the celiac artery (35 × 13 mm). The patient was admitted to the Department of Pediatrics of the Meyer Children’s Hospital for further diagnostic investigations.
Physical examination revealed palpable spleen and liver, a right inguinal lymph node of 1 cm and a lymph node in supraclavicular location, without any further objective anomaly. She had no fever. Initial laboratory tests found microcytic iron deficiency anemia (Hb = 9.8 g/dl, MCV = 65.5 ft., Ferritin = 4 ng/ml), with normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), normal total protein and protein electrophoresis, a slight increase of lipase and colic acids with normal amylase. Blood biochemistry for kidney and liver function and urinalysis were normal. Primary immunologic work-up including lymphocyte subset and immunoglobulin levels were normal. Tests for malignancies (tumor markers and peripheral blood smear) and infectious investigations, including Mantoux Test and IGRA Assay resulted negative.
Chest X-ray was negative. Magnetic resonance imaging (MRI) examination of the superior and inferior abdomen with contrast medium confirmed increased liver dimensions and its structural inhomogeneity with zones of signal alteration: some nodular, other confluent. It also revealed increased spleen size with zones of nodular signal alteration and multiple nodular formations in the following locations: hepatic hilar, mesenteric, lombo-aortic, at the retrocavity of the epiploon, and the greatest one in front of the celiac artery (diameter > 3.5 cm).
Suspecting a systemic lymphoproliferative disease, we performed liver and lymph node ultrasound-guided biopsy, which showed negativity of Polymerase chain reaction (PCR) for potential agents of infectious diseases (including Mycobacteria and Bartonella species) on lymph node material, while it highlighted a non-necrotizing granulomatous inflammation, resembling sarcoidosis, and aspects of non-specific inflammation of the liver. (Fig. , ).
Subsequently, we carried out measurements of serum and urinary calcium, serum phosphorus, Angiotensin-Converting Enzyme (ACE), followed by a complete cardiac evaluation, and a complete ophthalmologic evaluation (including slit lamp), all of which resulted within normality.
At this point, given the biopsy results, we performed further lung studies: pulmonary function tests which showed mild restriction and decreased alveolar capillary diffusion. The chest X-Ray revaluation revealed a pattern compatible with mild fibrosis and enlarged lymph nodes. We decided to carry out a high-resolution chest computed tomography (CT), which showed widespread fibrous strands and multiple enlarged lymph nodes (right paratracheal area, at the supraaortic trunk origin, subcarinal, with the largest in this location measuring 30 × 17 mm, pericardiophrenic, bilaterally at axillary level and along the mammary vessels). The bronchoscopic investigation with analysis of the broncho-alveolar lavage (BAL) fluid revealed: macrophages 70%, neutrophils 4% and lymphocytes 26% with a CD4/CD8 ratio of 9.2 (pathological value > 3.5).
Based on these results, we carried out further investigations on liver tissue and lymph node with histochemical techniques: CD68 + nodules were found, suggestive of microgranulomas (Fig. and ).
Having ruled out other diagnoses, with suggestive histological findings in two different tissues (liver and lymph nodes) and considering lung involvement, we made the diagnosis of pediatric-onset adult sarcoidosis.
During hospitalization, the condition of the child had always been good and she had always been afebrile. Considering lymph node hypertrophy and the signs of initial portal hypertension (due to compression of the hepatic vessels), we started therapy with prednisone 40 mg/day, and subsequent cross-therapy with mycophenolate mofetil (250 mg/m2 increasing up to 1 g/m2).
The girl came back to our attention a month after discharge for a follow-up visit: she was found in good general condition, with hepatomegaly and without other clinical signs or symptoms. A brain MRI was performed in order to rule out cerebral involvement and it revealed normal findings. One year later she maintained good clinical condition and normal laboratory tests, therefore MMF was gradually reduced and definitively suspended after 18 months. Now her periodic follow up consist of clinical and laboratory evaluation every 6 months and annual pulmonary function tests, unless clinical or laboratory new findings. |
pmc-6025733-1 | The proband, 9 year old Sinhalese boy born to unrelated parents after an uncomplicated pregnancy who has an elder sister (14 years) and a younger sister (2 years) presented to our tertiary care children’s hospital in Sri Lanka with abdominal pain and gross haematuria since two weeks. Patient has had repeated episodes of haematuria in the past but urine tests were not available. There was no family history of renal stones. Physical examination was unremarkable. Ultrasonography of abdomen revealed a 2 cm calculus in the right middle moiety of kidney non obstructing. Ultrasound scan of family members was not performed. Biochemical investigations of the proband revealed a persistent hypouricemia (sUA 97 μmol/L, 93 μmol/L). Other biochemical investigations including liver and renal functions were within normal limits. Fractional excretion of uric acid was 33%. Secondary causes of hypouricemia were ruled out. Decreased blood concentrations of UA together with markedly elevated fractional excretion of uric acid (FE-UA) caused us to suspect RHUC and therefore a genetic analysis of the SLC22A12 and SLC2A9 gene was performed after informed consent. Probands parents and other two siblings were asymptomatic.
The sequencing analysis of SLC22A12 revealed a previously identified missence variant c.1400C > T (p.T467 M, rs200104135) in heterozygous state []. The sequencing analysis of SLC2A9 revealed two common variants: homozygous c.757G > A (p.V282I, rs16890979) and heterozygous c.962C > T (p.P350L, rs2280205). Analysis of family members identified p.T467 M variant in father of proband (41 year old male: sUA 172 μmol/L, FE-UA 13%) and the two siblings (14 year old sister: sUA 81 μmol/L, FE-UA 15%; two year old sister: sUA 86 μmol/L, FE-UA 25%). The analysis of mother of proband revealed only heterozygous variants p.V2821 and p.P350L in SLC2A9 (sUA 179 μmol/L, FE-UA 9%). Clinical, biochemical and genetic data are shown in Table . Figure shows the electropherograms of part of the SLC2A9 and SLC22A12 gene sequence of the family members.
Genomic DNA was extracted from blood sample and/or dry blood spot using a QIAmp DNA Mini Kit (QiagenGmbH, Hilden, Germany) in the Institute of Rheumatology, Prague, Czech Republic. All protein-coding exons of SLC22A12 and SLC2A9 were amplified using polymerase chain reaction (PCR) and purified using a PCR DNA Fragments Extraction Kit (Geneaid, Taiwan). DNA sequencing was performed with a DNA sequencer (Applied Biosystems 3130 Genetic Analyzer; Applied Biosystems, USA). Primer sequences and PCR conditions used for amplification were described previously [, , ]. The reference genomic sequence was defined as version NC_000011.8, region 64,114,688..64126396, NM_144585.3 for SLC22A12; NM_020041.2, NP-064425.2,SNP source dbSNP 132 for SLC2A9. |
pmc-6025820-1 | A 76-year-old man was referred to our hospital for having lower back pain for 5 months, which was suspected to be L2/3 spondylitis on magnetic resonance imaging (MRI). He had previously undergone cervical laminoplasty for ossification of the posterior longitudinal ligament and diffuse idiopathic skeletal hyperostosis 19 years earlier. He had a history of hypertension and diabetes. Although a history of BCG vaccination was unknown, he had no previous history of tuberculosis infection. He had also undergone transurethral resection of a bladder tumor (TUR-Bt) and had been treated with intravesical mitomycin C (MMC) for the bladder cancer 1.5 years earlier. Four months later, he again underwent TUR-Bt, received intravesical MMC, and started BCG therapy for the recurrence of bladder cancer. After the sixth course of intravesical BCG therapy, he was aware of systemic weakness and loss of appetite, and was unable to walk. He appeared to have septic shock and therefore was treated in the intensive care unit. In spite of systemic analyses, the source of his infection and the causative bacteria could not be identified. He was subsequently diagnosed with hypercytokinemia caused by BCG therapy. He showed clinical improvement without the administration of antituberculosis drugs, and was discharged 9 months before he came to our hospital.
Except for a temperature of 37.2 °C, his vital signs were within normal limits. Although there were no motor and sensory disturbances in the legs, he was unable to walk owing to lower back pain. Physical examination demonstrated vertebral tenderness at the L2/3 level. Laboratory analysis demonstrated a normal white blood cell (WBC) count of 6300 /μL, a high erythrocyte sedimentation rate (ESR) of 53 mm/h, and a high C-reactive protein (CRP) level of 2.7 mg/dL. There were no other abnormal laboratory findings regarding anemic changes, kidney function, or liver function. The patient did not receive tuberculin skin testing.
There were no notable findings on electrocardiogram or chest X-ray. X-ray of the lumbar spine displayed collapsed endplates of L2/3. Sagittal T1-weighted MRI displayed a decreased signal in the L2/3 disc and the vertebral bodies (Fig. ). Sagittal T2-weighted MRI displayed an increased signal in the L2/3 disc and fluid collection in the anterior part of the vertebral bodies (Fig. ). Axial T2-weighted MRI displayed an increased signal around the posterior area of the vertebral bodies, which extended into the left epidural space and reached the peripheral muscle tissue and the area near the aorta (Fig. ).
On the second day of hospitalization, the patient underwent an L2/3 disc biopsy, but the general bacteria culture was negative, and the smear was negative for Ziehl-Neelsen staining. The patient’s blood culture was negative, and the result of T-SPOT.TB® (T-SPOT), which is a type of interferon-gamma release assay (IGRA), were also negative; the number of spots for both 6-kDa early secretory antigenic target (ESAT-6) and 10-kDa culture filtrate antigen (CFP-10) was 5 or less. The causative bacteria remained unidentified and therefore he was started on empirical therapy with intravenous ceftriaxone. On the fifth day of hospitalization, a plain computed tomography scan, which was performed for systemic examination, showed soft tissue development in the adjacent abdominal aorta at the L3 level (Fig. ), which was suspected to be an infectious aortic aneurysm. A 2-stage operation was planned for the spondylitis with adjacent infectious aortic aneurysm, to prevent rupture of the infectious aortic aneurysm, obtain spine stabilization, drain the abscess and make a diagnosis. On the tenth day in hospital, because the risk of rupture was considered to be low, the patient underwent an L2/3 laminectomy followed by posterior fixation using percutaneous pedicle screws at T12, L1, L4, and L5 as the first stage. Specimen cultures of the lumbar vertebrae, yellow ligament, necrotic tissue, etc., were negative for general bacteria, specimen smears were also negative for Ziehl-Neelsen staining, and there were no pathological findings of caseating granuloma or necrosis. On the fiftieth day of hospitalization, because the infection had been controlled but the inflammatory response was sustained, he underwent replacement of the aneurysm with a synthetic graft by vascular surgeons, and lesion curettage and L2/3 anterior interbody fusion by iliac bone transplantation as the second stage. Spinal surgery was performed in the transabdominal approach owing to the risk of rupture. On pathological analyses, the L2/3 intervertebral disc, vertebral bone, and tissue surrounding the vertebral bone and aorta showed caseating granuloma and necrosis with multinucleated giant cells and epithelioid cells upon hematoxylin-eosin staining, and positive bacilli upon Ziehl-Neelsen staining. The tuberculosis-polymerase chain reaction (Tb-PCR) result of the tissue was also positive, using COBAS® TaqMan® MTB Test, which is a real-time PCR system targeting the 16S rRNA gene region of Mycobacterium tuberculosis complex DNA. Owing to the patient’s history of BCG therapy, negative T-SPOT, pathological findings, and positive Tb-PCR, the pathogenic bacteria of the spondylitis was considered to be BCG. We then started multidrug therapy with antituberculosis drugs, including isoniazid (INH), rifampin (RFP), and ethambutol (EB), because BCG is typically resistant to pyrazinamide (PZA). PCR-based genomic deletion analysis was performed using the specimens to distinguish BCG from the other M. tuberculosis complexes. Specifically, multiplex PCR was performed utilizing region of difference 1 (RD1), which is present in the DNA of other M. tuberculosis complexes but is deleted in the DNA of BCG []. Primers ET1, ET2 and ET3 bind and amplify a 190-bp region in BCG, whereas a 160-bp region is amplified in the other M. tuberculosis complexes, as observed by electrophoresis on an agarose gel. A clinical isolate sample from our patient was identified as BCG with a deletion in RD1 (Fig. ). Specimen cultures from the first-stage and second-stage operation were later identified as members of the M. tuberculosis complex using a mycobacteria growth indicator tube. After therapeutic intervention, the patient’s WBC count, ESR level, and CRP level were improved and MRI displayed no signs of active infection in the spine, epidural space, peripheral muscle tissue, or aorta. On the ninetieth day after hospitalization, the patient was discharged from our hospital and transferred to a different hospital for physical rehabilitation. |
pmc-6025822-1 | A 70-year-old man with a history of hypertension, insulin-dependent diabetes mellitus, and a carotid endarterectomy was admitted to our emergency department with persisting and progressive angina for two hours. Moreover, he complained about general malaise and decreased exercise tolerance in the week prior to hospital admission. On physical examination, cardiac sounds were normal on auscultation. His blood pressure was 110/60 mm Hg and heart rate was 90 bpm. On admission, serum troponin T was 956 ng/L (normal range [NR] < 14 ng/L), creatine kinase myocardial band (CK-MB) 18 U/L (NR < 25 ng/L), creatine kinase (CK) 132 U/L (NR < 132 ng/L), low-density lipoprotein (LDL) cholesterol 3.4 mmol/L, high-density lipoprotein (HDL) cholesterol 0.8 mmol/L, triglyceride 0.75 mmol/L, and C reactive protein 150 mg/L (NR < 5 mg/L). His electrocardiogram (ECG) showed sinustachycardia (118/min) with ST-segment elevation in leads II, III, aVF and V5–6 and ST-segment depression in leads V1-V2. Coronary angiography was performed within one hour of hospital admission and revealed single-vessel coronary artery disease and the patient underwent a percutaneous coronary intervention of the circumflex coronary with placement of a drug-eluting stent. After the procedure, a Thrombolysis In Myocardial Infarction (TIMI) grade 2 flow was achieved in the AMI culprit coronary artery. Peri-procedural hypotension was treated with infusion of 2 l of 0.9% sodium chloride and dobutamine infusion. Postprocedural transthoracic echocardiography showed a moderate left ventricular function with a left ventricular ejection fraction of 40–45% and trivial mitral and tricuspid regurgitation.
Fifty days after PCI the patient experienced progressive fatigue and chest pain with haemodynamic instability. Transthoracic echocardiography showed a covered left ventricular free wall rupture (LVFWR) of the lateral wall and extensive pericardial fluid and inflow obstruction. The free wall rupture was in close proximity to the anterolateral papillary muscle (ALPM), but did not lead to significant mitral regurgitation. The transthoracic echocardiographic images are shown in Fig. .
The patient was brought to the operation room for emergent repair of the rupture. The surgical technique is described and shown in Fig. . The patient was weaned of cardiopulmonary bypass through the use of mild doses of inotropes. Transesophageal echocardiography showed a good result without significant mitral regurgitation. By carefully avoiding damage to the ALPM during the procedure we were able to avoid additional mitral valve repair or replacement.
Postoperative recovery was uneventful and the patient was discharged 12 days after the operation. More than a year later, the patient did not experience any subsequent cardiac events and his functional status was similar to the level before the episode of myocardial infarction and rupture. |
pmc-6025831-1 | A 23-year-old French man of African origin, an elite football player, sustained a midshaft anterior cortex tibial stress fracture 2.5 years ago. Initially, he was treated with cast immobilization, no weight bearing for 3 months, ultrasound stimulation, and electromagnetic field therapy. The fracture did not heal; he had pain during gait, so he continued no weight bearing for 3 additional months. After that period, the fracture site still was not healed, so he underwent an operation performed by his team doctor. In this operation, the medullary canal of his tibia was reamed and an im nail was inserted.
Unfortunately, the fracture site did not consolidate again, even 18-months postoperatively, so he presented to our clinic for counseling. It was obvious from the X-ray (Fig. ) that a nonunion of the fracture had occurred.
He did not smoke tobacco and he had a free medical history. When he presented to our clinic, the area at the fracture site was swollen and painful when palpated. The pain got worse when he attempted to walk with full weight bearing, so he had to use crutches. An examination of the peripheral nervous system of his lower extremities did not provide us with any pathologic findings. In addition, the laboratory examinations for possible endocrine or metabolic disorders were negative (Table ), so he was advised to have a reoperation to address this nonunion. The treatment options for such cases include nail exchange, drilling of the fracture site, bone grafting, or removal of the nail and internal fixation with a plate. We performed a tension band plate fixation, which is a technique already described for the treatment of anterior tibial stress fractures that failed non-operative treatment [], with bone grafting and without removing the nail.
A longitudinal incision was made just lateral to the anterior tibial crest centered over the fracture site. The fascia over the tibialis anterior was divided, the muscle lifted off and the fracture site was visualized. The necrotic bone and callus at the fracture site was debrided with the use of an osteotome and a curette. Transverse drilling around the fracture site was done to promote healing and osteoblastic activity. Bone marrow from the ipsilateral iliac crest was inserted into the fracture site and a tension band plate was applied over the im nail.
We used a 6-hole, 4.5 mm locking compression plate. The plate was prebended and the screws were placed in a compression manner to achieve a tension band effect to the fracture site. A cortical screw was put first to the distal hole closest to the fracture site and then a cortical screw to the closest hole proximal to the fracture site to ensure compression of the fracture. Consequently, one unicortical locking screw was inserted proximally to the fracture site and the other two distally. With the use of locking and non-locking screws we minimized the pressure at the periosteum, which can damage blood supply to the poorly vascularized bone. The screws were angled in a different axis in order to bypass the nail (Fig. ).
Postoperatively, our patient was advised to wear an orthotic boot and to not bear weight for 6 weeks. Range of motion exercise involving knee and ankle and isometric exercises were initiated immediately postoperatively. After 6 weeks he progressed to weight bearing as tolerated. At 3 months postoperatively he was pain free and started light jogging, swimming, and plyometric and core stabilization exercises. At 6 months postoperatively the complete radiologic union of the fracture was evident (Figs. and ). He was symptom free; he resumed at that time a full training program and he returned to play football 6 months postoperatively at his preinjury high competition level. |
pmc-6026101-1 | A 16-year-old boy with bilateral TMJ ankylosis was referred to the oral and maxillofacial surgery department of Tehran University of Medical Sciences. The bilateral TMJ ankylosis had been induced due to trauma when the patient was 4 years old. He had undergone TMJ surgery twice, but the operations had been unsuccessful and the TMJ ankylosis relapsed ().
The clinical examination revealed no systemic diseases. The patient’s maximum incisal opening was 11mm. Because of the old injuries and unsuccessful operations, the mandibular deficiency had developed. The patient was experiencing sleeping disorders and mostly slept in a prone or a sitting position due to respiratory problems. The lateral and forward motions of the mandible were restricted. Based on the patient’s condition and the past surgical history, a two-step treatment was performed. First, the gap arthroplasty method was applied, and afterwards, DO was performed.
The gap arthroplasty surgery was followed by physiotherapy. Approximately 3 to 10 days after the surgery, the patient was put on a soft diet and began the jaw-opening exercises. Three to four weeks after the surgery, a normal diet was started. After the discharge, the patient was visited once a week to evaluate the changes.
The osteodistractor was installed four months later (). After the installation, since the condylar stop had been removed in this case, and there was a possibility of upward and backward shift of the proximal mandibular segment, we used a custom-made device to prevent these movements. The Sh-device has a curved metal rod and two oval stoppers that can be connected to two areas, one to the patient’s forehead and another to the upper lip (below the nose). The stoppers are made of a firm clear plastic; the inner stopper surface is covered with a layer of soft spongy tissue that provides comfort for the patient upon using the Sh-device (). The stoppers are attached to the back of the patient’s head by two elastic bands, which keep the device on the patient’s face. The elastic bands, which are attached to the orthodontic hooks on the mandibular premolars or molars, are connected to a small piece at the bottom of the lower stopper. The main pressure/traction of the Sh-device was applied on the distal mandibular segment, and the Sh-device prevented the proximal mandibular segment from moving upward and backward; therefore, the greatest displacement occurred at the distal mandibular segment. The mandible was driven forward at a rate of 0.5mm per day.
After one month, we separated the Sh-device, and the mandible moved about 15 to 20mm forwards. The patient’s breathing and sleeping improved. At the 8-year follow-up, the patient’s profile was satisfactory. The patient’s maximum incisal opening increased to 38mm (). |
pmc-6026343-1 | A 71-year-old man, originally from North Africa, with a history of insulin-dependent diabetes mellitus, presented to our emergency department with a 2-month history of nonspecific abdominal symptoms: meteorism (bloating) and a subjective feeling of abdominal enlargement. Diarrhea, loss of appetite, weight loss, persistent fever, night sweats, headaches, anxiety, gastric ulcer disease, or skin rash were not reported. He did not report a neoplasm in the past and he had not undergone an abdominal examination before. He could not recall any episodes of pancreatitis or suffering from gall bladder stones. He had undergone a computed tomography (CT) scan a few days before which showed a tumor in the pancreatic head and he was referred to our clinic. Diabetes mellitus occurred 20 years ago and he was initially treated with orally administered anti-diabetic drugs for more than 12 years. Apart from diabetes and arterial hypertension he had no previous medical or surgical history. He has been treated with two different anti-hypertensives, two diuretics, acetylsalicylic acid, and insulin glargine. He reported an allergy to metformin. He did not smoke tobacco or drink alcohol.
On general physical examination, he was conscious and oriented and in fair general condition. He appeared to be in a good nutritional state (height 165 cm, weight 73 kg, body mass index 26.8 kg/m2). His lungs were clear to auscultation and percussion bilaterally. His heart examination was also normal. He had a soft, non-tender abdomen without any palpable masses. Icterus and lymphadenopathy were absent. His vital signs were normal.
A routine laboratory analysis showed the following abnormal values: hemoglobin 12.5 g/dl (13.5–17.5), hematocrit 25% (40–53), mean corpuscular volume (MCV) 78 fl (82–98), uric acid 10.2 mg/dl (< 7.0), creatinine 1.8 mg/dl (< 1.4), and random serum glucose 148 mg/dl. Transaminases and cholestasis parameter were normal. Glycated hemoglobin (HbA1c) was 6.9% (52 mmol/mol). The serum tumor markers carcinoembryonic antigen (CEA) and cancer antigen 19–9 (CA19–9) were in normal range. Serum pancreatic lipase was slightly elevated (88 U/l, reference range < 65 U/l). The pancreatic elastase in stool was normal. There was no clinical evidence for exocrine pancreatic insufficiency.
An ultrasound of his abdomen revealed a tumor of the uncinate process of the pancreas. The endoscopic ultrasound showed a mass in the area between the neck and the body of his pancreas, measuring approximately 24 mm in its largest dimension. The tumor compressed his splenic vein; however, there were no signs of infiltration. Contrast-enhanced CT demonstrated an almost 3 cm round, quite well-defined and homogeneous tumor formation in the area between the neck and absent body of his pancreas (Fig. ). The tail of the pancreas was absent as well. The tumor showed a slightly arterial hypervascular enhancement and a central calcification in the shape of a dot. There was no central hypoperfusion or necrosis. The imaging findings were not typically suggestive of exocrine pancreatic carcinoma or pancreatic endocrine tumor. After discussing the case at our interdisciplinary tumor board, we decided to perform a biopsy.
The initial fine-needle aspiration was performed via endoscopic ultrasound. However, the pathological analysis did not detect tumor cells in the aspiration material.
In the next step our patient underwent CT-guided biopsy of the mass. A histopathological examination (Fig. ) revealed the typical aspect of a well-differentiated neuroendocrine tumor with solid aggregates of isomorphic tumor cells. Immunohistochemistry showed intensive cytoplasmic staining for synaptophysin (Fig. ) and nuclear staining for Ki-67 in less than 2% of the tumor cells (Fig. ). No gastrin expression could be detected by immunohistochemistry.
Our patient underwent pancreas resection because of the presence of a neuroendocrine tumor. On macroscopic examination, the tumor was 1.8 cm in maximum diameter (TNM staging, pT1). There was no vascular invasion present. None of the three lymph nodes was metastatic (TNM staging, pN0). The active proliferative rate of Ki-67 (a pathological grading marker) was 5%.
Well-differentiated neuroendocrine tumors of the pancreas usually show the characteristic nested, trabecular, or gyriform pattern known from neuroendocrine neoplasms of other organs. There are, however, architectural and cytological variations in some tumors, including abortive gland formation or oncocytic and clear cell changes.
In our case, the differential diagnosis of the biopsy specimen was focused on a distinction from other epithelial pancreas neoplasms especially the solid variants of acinar cell carcinoma, solid pseudopapillary neoplasm, as well as pancreatoblastoma. The latter tumor types may also exhibit the nesting pattern observed in our case. Therefore, the intensive homogenous staining pattern for synaptophysin in our case provided an important argument for the diagnosis of a neuroendocrine tumor. This diagnosis was further corroborated in the resection specimen by the lack of features defining acinar cell carcinoma (for example, acinar differentiation) or pancreatoblastoma or solid papillary neoplasm (for example, pseudopapillary growth pattern).
Our patient underwent a 68gallium-DOTATOC positron emission tomography (PET)/CT scan 4 months later, which did not show increased metabolic uptake. Seven months after pancreas resection his HbA1c increased from 6.9 to 8.7%. This led us to modify his diabetes medication to a combination including insulin glargine, insulin glulisine, and metformin. |
pmc-6026501-1 | A 26-year-old right-handed white woman with no significant medical history was diagnosed as having MS in 2013 at age 22 and experienced ongoing radiologic activity on both glatiramer acetate and dimethyl fumarate. She transitioned to natalizumab in July 2014 to stabilize disease activity, and her JCV antibody index was positive at 3.58 prior to starting natalizumab. She became clinically and radiologically stable with the initiation of natalizumab until November 2016 when a surveillance MRI of her brain showed asymmetric confluent non-enhancing hyperintensities in the bilateral subcortical precentral gyri consistent with PML (Fig. , ). Cerebral spinal fluid (CSF) showed quantitative polymerase chain reaction (PCR) for JCV of 15 copies/ml, and other CSF studies were within normal limits. A diagnosis of PML was made based on the compatible neuroimaging findings along with the presence of JCV DNA in the CSF. Natalizumab was discontinued after 27 total treatments. Our patient was asymptomatic at the time of PML diagnosis, and she was highly functioning with an Expanded Disability Status Scale (EDSS) of 0. A decision was made to defer plasmapheresis at the time of diagnosis given her high functional status, subtle radiological change, and low viral titer. She was treated with orally administered mefloquine loading dose followed by 250 mg weekly and mirtazapine 15 mg daily.
Repeat MRI at 2 months following diagnosis showed no changes in her brain lesions. She remained asymptomatic until 3 months after diagnosis when she noticed mild dysmetria of her left hand that progressed to a tremor. The following month a repeat brain MRI revealed a few small enhancing lesions in her left frontal lobe suggestive of IRIS (Fig. , ). The hyperintensities in the bilateral precentral gyri remained stable. Imaging of her cervical spine revealed a new non-enhancing cord lesion. She was then treated for 5 days with intravenously administered immunoglobulin and restarted on glatiramer acetate for MS treatment. A repeat CSF examination in February 2017 showed JCV PCR of 31 copies/ml.
Five months following her diagnosis, a repeat brain MRI showed interval development of T2 signal abnormality with mild enhancement in multiple areas including the brainstem, cerebellum, and bilateral cerebral hemispheres (Fig. , ). A repeat lumbar puncture was performed. JCV PCR in the CSF was undetectable. Mefloquine and mirtazapine were discontinued. Given the MRI findings, she was treated for ongoing inflammation associated with IRIS versus a possible exacerbation of her underlying MS with high-dose intravenously administered methylprednisolone (IVMP) 1500 mg daily for 3 days. She was then transitioned from glatiramer acetate to ocrelizumab for treatment of MS. Six months following her diagnosis she reported changes in left hand dexterity and right upper extremity phasic spasms. A repeat lumbar puncture was performed and JCV PCR remained undetectable. She continued MRI surveillance followed by treatment with high-dose IVMP for a total of six courses until there was significant resolution of enhancement on her brain MRI (Fig. , ). Following treatment, she has residual left hand dysmetria and tremor as well as right upper extremity phasic spasms. At 1-year follow-up, her EDSS is 2.0. |
pmc-6026506-1 | A 67 years old lady came to the out-patient department with a history of acute onset jaw tremor, with tremor predominantly in both upper limbs approximately 2 months prior to consultation. Her symptoms had progressed over a period of 24–48 h and remained static until the consultation. She did not have features of non-motor symptoms to suggest a diagnosis of idiopathic PD.
There was no history of previous stroke or vascular risk factors for stroke. She had not been on any medication which could cause extra-pyramidal symptoms.
General physical examination was normal. Neurological examination revealed hypomimia of the face with cogwheel rigidity and bradykinesia bilaterally (right more than left), predominantly in the upper limbs without pyramidal signs (the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III; item 18–32 was 36). She had a marked tremor of the jaw at rest (Additional file 1). When she was asked to open her mouth the tremor was re-emergent (Additional file 2). There were no pyramidal signs. The rest of the neurological examination was normal which included cognition, speech, cerebellar function and bladder function.
Non-contrast CT scan of her brain revealed an infarction in the region of the putamen on the left with no evidence of diffuse subcortical white matter ischemia or extension to the caudate nucleus (Fig. ). A vascular screen for stroke risk factors was negative. A DAT scan was unavailable due to lack of resources and financial constraints.
She was treated with a trial of levodopa (300 mg per day) and anti-platelet therapy which resulted in marked reduction in her jaw tremor and other extrapyramidal symptoms after 1 month of follow-up (UPDRS part III improved from 36 to 24). |
pmc-6026507-1 | A 55-year-old Japanese woman had developed right-lateral chest and back pain 2 months prior to admission to our hospital. Thirteen years previously, she had undergone concurrent bilateral salpingo-oophorectomy and total hysterectomy for right ovarian tumor in other institution. She had no past history of other neoplasms. Physical examination revealed deep-tendon hyperreflexia in the lower extremities but no muscle weakness. Blood tests were unremarkable apart from a high serum concentration of cancer antigen 125 (134 U/mL; cutoff value, 35 U/mL). On fluorodeoxyglucose (FDG) positron emission tomography the maximum standardized uptake value (SUVmax) was 6.6 in the right paraspinal region at the level of Th12 (Fig. ) and 8.8 in the right thyroid lobe; however, fine-needle aspiration cytology of the latter yielded no evidence of malignancy. CT scan and magnetic resonance imaging (MRI) revealed an irregular mass in the right arch of Th12 vertebral bone that protruded into the spinal canal through the intervertebral foramen and was infiltrating surrounding soft tissue, the whole mass being of 35 × 78 × 36 mm (Fig. -). No primary tumor was detected in other organs or the abdominal or pleural cavities. Pathological examination of a CT-guided needle biopsy of the paraspinal lesion demonstrated papillary proliferation of epithelial cells with blunt nuclear atypia against a fibrotic background with psammomatous calcification (Fig. ). Immunohistochemically, the neoplastic cells were positive for paired box 8 (PAX8) (Roche Diagnostics; Basel, Switzerland), estrogen receptor (ER) (Roche Diagnostics), and Wilms’ tumor 1 (WT1) (Roche Diagnostics), but negative for thyroglobulin (Nichirei; Tokyo, Japan) (Fig. ), thyroid transcription factor 1 (TTF1) (Roche Diagnostics), progesterone receptor (Roche Diagnostics), S100 protein (Roche Diagnostics), and calretinin (Roche Diagnostics). Staining for P53 (Roche Diagnostics) showed a non-mutational “wild type” pattern (Fig. ). Because the lesion was suspected of being a metastatic neoplasm from the previous ovarian tumor, we obtained the relevant clinicopathologic and operative records and found that our patient had had a 13- × 11- × 9-cm cystic tumor that did not involve the ovarian surface (Fig. ). Peritoneal cytology was negative; however, the tumor had been ruptured intraoperatively. Lymph-node biopsy was not performed during the original surgery. The six slides available for microscopic review in retrospect, which included all the 6 sections (1 on each slide) submitted for the previous diagnosis of the primary tumor, showed cuboidal to columnar epithelium with minimal cytologic atypia proliferating in hierarchical branches with no invasive features, micropapillary components, or peritoneal implants (Fig. –), the diagnosis being conventional Stage IC1 SBT/APST according to the current World Health Organization (WHO) and International Federation of Gynecology and Obstetrics (FIGO) 2014 classifications. All the above-listed immunochemistry markers were identical in the previous ovarian tumor and the present paraspinal neoplasm, except for Ki-67 (Agilent Technologies; Santa Clara, CA, USA), which had labeling indices of 1 and 5%, respectively. It was therefore concluded that the paraspinal lesion was a bone metastasis of transformed LGSC originating from the previous SBT/APST in the right ovary. The patient underwent radiotherapy (30 Gray in 10 fractions) for the paraspinal lesion, which relieved her pain, followed by chemotherapy treatment with paclitaxel and carboplatin plus bevacizumab. She remains alive with right-sided pleural effusion and suspected metastases in the Th3 and Th4 vertebrae 168 months after the initial surgery.
Neither the primary nor metastatic tumor harbored KRAS mutation (codon 12, 13, 59, 61, 117, or 146) according to polymerase chain reaction (PCR) using a reverse sequence-specific oligonucleotide methodology (LSI Medience; Tokyo, Japan), nor BRAF V600E mutation according to real-time PCR (LSI Medience). |
pmc-6026788-1 | A 35-year-old female (body weight 60.5 kg; height 1.55 m; body fat 16%; back squat 143 kg; front squat 125 kg; clean 97 kg; snatch 63 kg) without medical history of disease presented worsening abdominal pain approximately 24 h after completing a rigorous extreme conditioning competition (), which consisted of two days of five workouts. She was healthy overall and had been active in ECP over the previous five years and trained four or five times per week. The patient gave informed written consent for the use of her clinical and personal data in this paper.
The patient visited her physician one day after the ECP competition and was found to have a serum CK of 43,322 U/L. However, after receiving initial medical attention, she was sent home with instructions to take Tenoxicam (anti-inflammatory drug), bed rest, and drink plenty of water. On the third day post-competition, the pain and muscle swelling did not diminished, and she checked into an emergency room. At this stage her CK concentration was tested again and was 77,590 U/L. However, her kidney function, as indicated by blood urea, creatinine, sodium, and potassium concentrations was normal. On the other hand, her liver enzymes were elevated (aspartate aminotransferase (AST) of 477 U/L and alanine amino transferase (ALT) of 74 U/L). Chronological values of serum biochemistry and associated biomarkers over 25 days of follow-up are presented in . The patient was diagnosed with rhabdomyolysis by the medical attending physician and was treated with aggressive intravenous fluid resuscitation.
She was discharged on the fourth day of hospitalization and she was advised to avoid intense exercise. A follow-up examination revealed that her serum level of CK was still elevated to 3034 U/L on the 10th day and 1257 U/L on the 25th day following the ECP competition (). The subject reported myalgia even 25 days after the ECP competition. |
pmc-6026928-1 | The patient, a 46-year-old female, presented to our department with complaints of continuous urinary incontinence. Her medical history included laparoscopic hysterectomy because of uterine myoma 2 months before her visit. Complete blood count, routine biochemistry parameters, urinalysis, urine culture, and urinary system ultrasonography results were all normal. We identified a 5-mm wide fistula between the bladder trigone and the upper part of the vaginal vault with flexible cystoscopy at the outpatient clinic. The patient was catheterized for 3 weeks. The patient who had catheterization failure underwent transvesicoscopic bipolar sealing of the vesicovaginal fistula (TBSF) after 3 months from her primary gynecologic surgery. The patient signed an informed consent form after she was advised on the use of the novel modified surgical procedure.
The operation was conducted with the patient in lithotomy position under spinal anesthesia. A prophylactic antibiotic (second-generation cephalosporin) was given half an hour before the induction. The VVF was identified with a cystoscope using insufflation of gas and it was verified by a guidewire (). The vagina was packed with vaseline-soaked gauze to prevent leakage during bladder filling and escape of CO2 during vesicoscopy. A 5-mm laparoscopic port was placed into the bladder under cystoscopic guidance in the lateral of the midline, halfway between the umbilicus and symphysis pubis. The second 5-mm port was placed into the bladder laterally at the midline and inferior to the first port (). A cystoscope was used as a transurethral camera for vesicoscopy. Bladder mucosa and muscular layer were gripped with a forceps and raised up for a multilayer closure. The fistula tract was grasped and sealed by an EBVS (LigaSure™ 5 mm blunt tip 37 cm sealer; Medtronic, Inc., Dublin, Ireland) (). An 18F Ryle's tube was kept in the bladder as a cystostomy through one of the existent ports. The bladder was also catheterized.
The operative time was 65 minutes. Blood loss was minimal and could not be measured in the case. There were no intraoperative or postoperative complications. The patient was allowed oral intake within 3 hours, to move within 12 hours postoperatively, and was discharged after removal of the cystostomy on the first postoperative day. The Foley catheter was kept in place for 3 weeks. An oral anticholinergic was given until the removal of the Foley catheter. The patient was instructed to return to our office 3 weeks after surgery for urethral Foley catheter removal and subsequent cystoscopic and vaginal inspection to confirm VVF repair (). During a 3-month follow-up, the patient remained continent, and the laboratory results were within normal range. |
pmc-6027573-1 | A 65-year old woman, on dialysis for 17 years, told her doctor she was exhausted and that she thought it was because she was taking too many drugs. The patient is an intelligent, independent, acculturated woman who lives alone in the French countryside.
Her medical history is complex: she was treated with lithium for about 20 years (from age 20 to 40). This was discontinued after she developed CKD; in recent years, under treatment with valproic acid and lamotrigine, her psychophysical balance has been good,.
She started smoking when she was 19 years old (30 cigarettes/day) and developed a smoke-related chronic obstructive pulmonary disease. She was obese in early adulthood; arterial hypertension was diagnosed at age 30 and type 2 diabetes at age 32, treated using oral hypoglycemic drugs, but she eventually lost about 20 kg, making it possible for antidiabetic drugs to be discontinued. She underwent total thyroidectomy for papillary carcinoma at age 41, and started levothyroxine therapy afterwards. Due to a progressive worsening of the kidney function she started hemodialysis at age 50. Her kidney disease was probably multifactorial (hypertension, diabetes, obesity, heavy smoking, lithium therapy).
Seven years after dialysis start, she underwent left hemicolectomy for colon adenocarcinoma, and two years later, left quadrantectomy followed by radiotherapy for ductal mammary adenocarcinoma. She underwent subtotal parathyroidectomy for severe tertiary hyperparathyroidism at age 62. Due to the presence of severe scoliosis, and the development of peripheral neuropathy, she uses painkillers regularly.
At the time of the present report, she was on thriceweekly hemodiafiltration, with good dialysis tolerance and high dialysis efficiency (Daugirdas 2 Kt/V: 1.6–1.8).
Her most recent treatment included antihypertensive drugs (spironolactone 100 mg, amlodipine 20 mg, perindopril 2.5 mg), antipsychotic drugs (valproic acid 600 mg, lamotrigine 100 mg), thyroid hormone (levothyroxine 150 μg), vitamin D, bicarbonate and calcium supplements (calcium carbonate 1 g, sodium bicarbonate 500 mg, vitamin D 25-OH 100,000 UI once a month), potassium and phosphate binders (sodium polystyrene sulphonate, on non-dialysis days and sevelamer 2.4 g per day), darbopoietin 20 μcg once weekly.
The clinical examination revealed a woman with good psychophysical balance, a moderate impairment in nutritional status, and a severe comorbidity burden (weight 54 Kg, height 155, BMI: 23 Kg/m2; subjective global assessment: B; malnutrition inflammation index: 10; Charlson index: 9). Apart from signs of chronic bronchitis, and an aortic 2/6 heart bruit, the clinical examination was unremarkable; arterial blood pressure was 150/90 mmHg, with mild orthostatic hypotension (135/80 mmHg); heart rate was 68 bpm. The most recent biochemical results are reported in Table .
The patient complained of severe fatigue, which had recently increased, and asked her doctor if he thought this could be the result of taking too many drugs.
In fact we thought our patient was right about pharmacologic interference, and felt that levothyroxine was the most likely candidate. A biochemical control disclosed a relevant increase in TSH (13.07 mU/L), as compared with her previous routine twice-yearly control (4.14 mU/L).
In retrospect, the levothyroxine dose was already high for a woman weighing about 55 Kg, and a reduction in the absorption of levothyroxine should already have been suspected.
Three of her chronic drugs display potential interference with levothyroxine: calcium carbonate, sevelamer and kayexelate. Since her sevelamer dose had recently been increased from 800 mg once daily to 800 mg 3 times per day, this long-scting phosphate binder was the most likely candidate. In keeping with this hypothesis, one month after discontinuation of sevelamer and modification of the timing of levothyroxine treatment (in the morning after night fasting) TSH was once more in the normal range. In the three months that followed, her levothyroxine dose was reduced to 100 micrograms per day. A further attempt to reintroduce sevelamer, taken at least 6 h after levothyroxine, led to a new increase in TSH (TSH 12.66 mUI/l), once more corrected by discontinuation of sevelamer.
Pubmed and EMBASE were explored (start to February 15th 2018) with the aim of retrieving papers related to dialysis, levothyroxine and phosphate binders. The following terms were employed: (a) dialysis, hemodialysis, hemodiafiltration, renal replacement therapy; (b) phosphate binder(s), sevelamer, calcium carbonate, calcium acetate, aluminum hydroxide, lanthanum carbonate; (c) levothyroxine, thyroid hormone replacement therapy. Due to the low number of papers retrieved by this search, a further search was performed combining (b) and (c). The searches, paper selection and data extraction were performed in duplicate (EC and VC); a further search on Google med did not lead to further papers. Discrepancies were resolved by discussion with a third party (GBP). A manual search of the reference lists from identified articles was done to identify additional articles. The search strategy and flow-chart is reported in Fig. .
Given the small number of papers retrieved, and their high heterogeneity, a meta-analysis was not performed, and the data were narratively discussed, in relation to other sources of information (data obtained in healthy volunteers, or in other diseases). |
pmc-6027734-1 | A 23-year-old Asian man was referred to the ER of Xiamen Chang Gung Memorial Hospital with a 1-day history of right-sided chest pain that had been aggravated for 1 hour. He had no known medical illnesses and was well until the evening prior to presentation, at which time he developed obvious right-sided chest pain radiating to his ipsilateral shoulder with persistent chest tightness. This tightness was described as sticking in nature, significantly worse on deep inspiration and with movement, and relieved by leaning forward or lying down. There was an associated dry cough but no hemoptysis. There was no history of trauma, injury, difficulty in breathing, or palpitations. He was tall and thin and described himself as otherwise quite healthy. He had never previously been admitted to a hospital. He reported no significant chronic medical history, such as primary hypertension, any type of heart disease, disturbed microcirculation, peripheral neuropathy, diabetes mellitus, an impaired immune system, malignancies, leukemia, the long-term administration of corticosteroids, liver cirrhosis, renal failure, urinary tract infection, or hemodialysis. He also reported no history of infection, such as tuberculosis, any type of hepatitis, or acquired immunodeficiency syndrome (AIDS). There was no prior history of traumas, blood transfusions, surgical procedures, or other serious events in his medical history. He had not lived in an epidemic area and had no history of toxin or radioactive exposure. He denied a personal or family history of bleeding diathesis but reported a 10-year history of smoking 8–10 cigarettes per day. He was an office worker by occupation. He had experienced similar symptoms on one occasion 4 years previously. No abnormalities were detected at that time, and his symptoms resolved.
A physical examination (PE) revealed a young man who was awake and alert but in mild to moderate painful distress. His respiratory rate was 22–26 breaths/minute with an oxygen saturation of 97%. His pulse was 96 beats/minute, his blood pressure was 115/74 mmHg, and his temperature was 36.7 °C. The examining physician noted slight tenderness along the right posterolateral chest wall along the eighth and tenth ribs. Breath sounds and percussion were documented as normal. An electrocardiogram revealed sinus rhythm with a normal axis. PSP was considered, and a standing chest X-ray (CXR) was requested. The radiographic findings revealed a right-sided PSP (approximately 30%) with a small amount of pleural effusion (Fig. ). A right thoracostomy tube (28-F, straight) was immediately placed under sterile conditions; approximately 50 mL of light red pleural effusion flowed out from the chest tube after placement, and good fluctuation of the water column in the drainage reservoir was observed. Another CXR was performed to evaluate the position of the thoracostomy tube and re-expansion of his right lung (Fig. ). Our patient’s vital signs stabilized, and his right-sided chest pain was apparently alleviated after chest tube placement; therefore, he was referred to the respiratory service with parenteral analgesia.
While in the respiratory department, approximately 420 mL of blood was drained from the thoracostomy tube over 15 minutes. He developed obvious hemodynamic instability with hypovolemic shock (his blood pressure dropped from 110/70 to 75/50 mmHg), and he was subsequently admitted to the cardiothoracic surgical ward after fluid resuscitation. During the 4 hours after admission, 750 mL of blood was drained through the thoracostomy tube. His hemoglobin level dropped from 12.6 g/dL to 9.2 g/dL. A prolonged prothrombin time (PT) of 19 seconds was noted (normal reference of 14 seconds). Packed red cells and fresh frozen plasma were administered to our patient. Vitamin K (10 mg) and tranexamic acid (1 g) were also administered parenterally. He was unable to undergo an emergency chest computed tomography scan as his vital signs remained unstable after fluid resuscitation. Alternatively, a bedside supine CXR was performed when he was temporarily hemodynamic stable (Fig. ). A primary SHP associated with right TP was considered based on the radiographic findings. A re-examination of his chest revealed markedly decreased air entry on the right side with mild tracheal deviation.
An emergency limited posterolateral thoracotomy was performed for resection of the bullae, ligation of the bleeding adhesion, and irrigation of the pleural cavity, and mechanical pleurodesis was implemented. Approximately 800 mL of blood and clots and a collapsed right lung with several apical bullae were observed. There was a small (less than 1.0 cm) tan lesion noted on the dome of the right side of his chest. Bullous apical tissues of the right lung adhering to the thoracic wall and adhesions at the region of the subclavian artery were identified as the source of bleeding. Aberrant blood vessels growing from the chest wall through the adhesion bands into the pleural lesion were thought to be torn once the lung collapsed. These bleeding blood vessels may also have arisen from the surface of ruptured bullae. Histopathology revealed that the bullous and string-like tissues were rich in blood vessels and were granulomatous.
Subsequently, the drainage from his chest tube became minimal. A standing CXR performed on day 6 of admission after removal of the thoracostomy tube showed complete re-expansion of his right lung. His hemoglobin level rose to 10.1 g/dL after a transfusion of two units of packed red blood cells, and his PT normalized. He remained stable and was discharged within 1 week (6 days postoperatively). He returned to an out-patient department for follow-up two times. The right-sided posterolateral surgical incision had healed on the 14th postoperative day. Full expansion of lungs was confirmed using a standing CXR on the 14th postoperative day and at 3 months after discharge. He was healthy as usual with no complaints or illness. |
pmc-6027982-1 | A 62-year-old Caucasian man, nonsmoker, had recto-sigmoid carcinoma in September 2015. Initial investigations showed the cancer was T3, N2 and M0 (grade II adenocarcinoma). He received neoadjuvant chemoradiotherapy with Capecitabine and radiotherapy (50Gy in 25 fractions) which was completed in December 2015.
Post chemo-radiotherapy, computed tomography (CT) scan and positron emission tomography (PET)/CT showed favourable rectal tumour response, but there were six small new liver lesions on magnetic resonance imaging (MRI). He was started on Modified De Gramont regimen plus Oxaliplatin in March 2016, Panitumumab was added in May 2016 as K-RAS was wild-type. Reassessment CT scan, MRI and PET scans in September 2016 showed a very good response in the liver and rectal primary lesions with no evidence of extra-hepatic disease. Only two lesions had been identified in the liver MRI while the rest of the lesions disappeared (). He underwent resection of the rectal disease with loop ileostomy by end of January 2017. The postoperative pathology showed a complete response. After recovery from bowel surgery, he continued on systemic chemotherapy and Panitumumab early March 2017 for three more cycles.
In May 2017, he was admitted with a 3-day history of fever, dry cough, progressive shortness of breath and decreased exercise tolerance. SpO2 was reduced at 88%. The total number of Panitumumab treatment cycles the patient received prior to this acute admission was 18. |
pmc-6028358-1 | A 54-year-old man was diagnosed with MPL mutated, primary myelofibrosis in 2004 with a hypercellular marrow, MF-2 fibrosis with megakaryocytic atypia, peripheral leukoerythroblastosis, splenomegaly, and an elevated lactate dehydrogenase. He was observed until 2010, when he was started on hydroxycarbamide for increasing symptoms. Prior to his 2011 enrollment in a clinical trial utilizing a novel JAK2 inhibitor, fedratinib, a bone marrow biopsy (Figure , Panel A; hematoxylin and eosin stain above, reticulin stain below, 10×) showed progressive megakaryocytic atypia and MF-3 fibrosis. Nearly 1 year into the trial, a repeat bone marrow (Figure , Panel B; hematoxylin and eosin stain above, reticulin stain below, 20×) was hypocellular with MF-3 fibrosis only in the cellular areas. The patient was taken off trial in 2013 and started on ruxolitinib. Repeat bone marrow biopsies in 2016 (Figure , Panel C; hematoxylin and eosin stain above, reticulin stain below, 10×) show a marrow comprised entirely of adipose tissue with osteosclerosis. Quantitative fat magnetic resonance (MR) imaging, utilizing methods reported separately, shows replacement of the marrow with fat. Representative transaxial MR images of the pelvis show water-only, and fat-only (Figure , top row) constituents. Arrows show the iliac crests. A representative pseudocolor display that depicts 100% fat as dark red and 0% fat as dark blue is shown (Figure , bottom row). The percent fat evident in the bone marrow imaging approximates that in the subcutaneous fat. After 3 bone marrow biopsies and the MR demonstrating this unusual transition of primary myelofibrosis to a fatty, aplastic appearing marrow, a repeat bone marrow in 2017 (Figure , Panel D; hematoxylin and eosin stain above, reticulin stain below, 20×) now showed a hypocellular marrow with histopathologic findings consistent with his marrow at the time of diagnosis. To our knowledge, this is the first case of a fibrotic marrow developing such an aplastic appearance in a patient treated with a JAK2 inhibitor. |
pmc-6028360-1 | A 61-year-old man had originally presented in 2012 with stage IVA oropharyngeal squamous cell carcinoma (SCC). He was treated with surgery followed by chemoradiation. Eighteen months later, he presented with a pancreatic mass and multiple osteolytic lesions. These were proven by biopsy to be metastatic oropharyngeal SCC. He was treated with carboplatin, 5-fluorouracil, and cetuximab with resolution of the pancreatic mass. On follow-up CT post 6 months of maintenance cetuximab, he was noted to have an asymptomatic left occipital brain metastasis for which he underwent stereotactic radiation. Three months later, he underwent left occipital craniotomy for relapsed disease. Imaging revealed a new enlarged paratracheal lymphadenopathy, and he was started on nivolumab at a dose of 3 mg/kg. After 3 months, he had a partial response. However, when he presented for day one of cycle 8, he complained of sudden onset fatigue. Brain MRI showed no new lesions. There was no evidence of pituitary inflammation. Blood work revealed a low random cortisol level of 1.8 μg/dL that did not have a satisfactory response to the ACTH stimulation test (Table ). With ACTH <0.5 pg/mL, primary adrenal insufficiency was ruled out, and he was started on dexamethasone followed by hydrocortisone for grade 2 immune-related central adrenal insufficiency. Because his fatigue was resolved, he resumed nivolumab treatment 5 weeks later. Restaging scans continue to show no evidence of progression. The patient continues to be on hydrocortisone with no complaints of fatigue. |
pmc-6028360-2 | A 61-year-old man with oral cavity SCC, who had been originally treated with surgery in 2011 for stage I disease, presented with cervical and left axillary lymphadenopathy after being lost to follow-up for over 4 years. Biopsy of the lymph nodes revealed metastatic SCC. He was then treated with carboplatin, 5-FU, and pembrolizumab on a trial. Pembrolizumab was dosed at 200 mg. After 4 cycles, his scans showed a partial response, but the patient presented with fatigue and hypotension to systolic blood pressure of 70 seconds. He was found to have a random cortisol level <0.5 μg/d that did not have a satisfactory response to the ACTH stimulation test (Table ). His ACTH level was <5 pg/mL. He was diagnosed with immune-related central adrenal insufficiency and was started on high-dose dexamethasone and later transitioned to hydrocortisone. Brain MRI did not show any inflammation of the pituitary stalk, and it was without metastatic lesions. Ten days later, his fatigue was resolved, and he resumed treatment with pembrolizumab. He continues to take hydrocortisone. |
pmc-6028360-3 | A 77-year-old man with stage IV lung SCC with metastasis to the liver was originally treated with carboplatin and nab-paclitaxel achieving a partial response. Unfortunately, he was found to have disease progression and was started on nivolumab 3 mg/kg. On subsequent scans, he continued to show stable disease. On day 1 of cycle 8, he complained of profound fatigue. He was found to have a random cortisol level of 1.3 μg/dL that did not have a satisfactory response to the ACTH stimulation test. His ACTH was <5 pg/mL (Table ). As immune-related central adrenal insufficiency was suspected, he was started on dexamethasone followed by hydrocortisone, and his symptoms were resolved immediately. The patient opted to discontinue nivolumab. Repeat scans 3 months postdiscontinuation of nivolumab continues to show no evidence of progression. He continues to be asymptomatic on hydrocortisone. |
pmc-6028363-1 | The patient, a 7-year and 6-month-old girl, was admitted to our hospital for premature thelarche. Her previous clinical history was negative. Her height was 131.5 cm (+1.06 SDS), and breast development was Tanner stage 3. LHRH test showed a LH peak equal to 17.7 mUI/mL and a FSH peak equal to 8.3 mUI/mL. 17β-estradiol level was 35 pg/mL; adrenal and thyroid functions and cancer markers (α-fetoprotein, βHCG, CEA) were in the normal range. The pelvic ultrasonography showed the presence of transitional uterus and ovaries with increased dimension and normal echostructure. Bone age assessed with Greulich and Pyle method was advanced (9 years). Nuclear magnetic resonance imaging of the pituitary and brain was normal. Diagnosis of idiopathic central precocious puberty was performed. She started a gonadotropin-releasing hormone (GnRH) analogue therapy with triptorelin i.m. 3.75 mg every 28 days, and after 6 months, a new LHRH test showed suppressed gonadotropin peaks (a LH peak equal to 0.67 mUI/mL and a FSH peak equal to 0.60 mUI/mL) confirming the efficacy of treatment.
At the age of 8 years and 4 months, the patient was admitted to our Emergency Department for the appearance of abdominal pain, burning sensation at neck and dyspnea occurred two hours after the last injection of i.m. triptorelin. At the examination, pruriginous whistles of about 20 mm were present on the whole body. Diagnosis of anaphylactic reactions was performed, and a treatment with systemic epinephrine and intravenous hydrocortisone was started with prompt resolution of symptoms. Skin prick tests performed the day after showed a positive result at very low dilution of the drug (1:10.000). As a result, therapy with triptorelin was discontinued. At 6 months of follow-up, no substantial progress of puberty or other anaphylactic reactions have been observed. |
pmc-6028364-1 | A 73-year-old man (body mass index: 23.5 kg/m2) complained of an urge to move the legs accompanied by an unpleasant sensation that he could not describe in words, worsened during rest and precipitated before night sleep, resulting in difficulty in falling asleep and nonrestorative sleep. His symptoms were relieved by mobilization and met the RLS diagnostic criteria. His IRLS score was 11. He felt very uncomfortable upon waking in the morning and claimed that even prolonged sleep did not relieve his fatigue. His average sleep duration was 10 hours. His physical examination and laboratory tests yielded normal findings, including a serous ferritin level of 69 ng/mL. He had been previously treated for hyperlipidemia and ischemic heart disease, and he declined the use of additional medication, apart from hypnotics.
I obtained a full-night diagnostic PSG recording while the patient was on hypnotic medication (zolpidem, 5 mg). I found that he experienced difficulty in initiating and maintaining sleep due to the discomfort associated with periodic leg movement (PLM) bursts. He received 4W-acuinjections of normal saline doses (0.25 mL each) supplemented with pentazocine (0.5 mg per dose) in both legs after the first 115 min of PSG. Immediately afterward, the patient felt a comfortable warmth to both legs, his discomfort subsided completely, and the PLMs ceased (Figure ).
Although short PLM bursts reappeared 124 minutes later, the patient reported remarkably restorative sleep in the morning. Most of the PLMs were observed during stage wakefulness periods, where slow eye movements were observed while EEG was alpha-rhythm dominant. Thus, discomfort accompanied by PLMs during drowsy periods, rather than wakefulness, seemed to disrupt his attempts to fall asleep.
After the 4W-acuinjections, his PLM index (number of PLMs/total recording h) decreased, and his percent sleep efficiency (total sleep time/total recording time × 100%) increased (Table ). |
pmc-6028364-2 | An 81-year-old man experienced symptoms including interrupted sleep (ie, waking up every 2 hours), excessive daytime sleepiness, and intolerable fatigue throughout the day. He experienced unpleasant paresthesia of the left leg urging to move. The symptoms worsened at rest and precipitated during the evening and night and were relieved by mobilization. His symptoms met the RLS diagnostic criteria, with an IRLS score of 16. However, he involuntarily tapped his right heel once every few seconds but did not report any discomfort related to this. Ordinarily, leg discomfort is bilateral in RLS. The patient's discomfort in the right leg could have been masked by his tapping; thus, his symptoms were consistent with RLS's typical presentation.
His average sleep duration was 9.5 hours. He was receiving pharmacotherapy for panic disorder, hypertension, hyperlipidemia, and dyspepsia. He refused additional pharmacotherapy. Laboratory tests returned normal findings, except for a ferritin level of 34.7 ng/mL and a hypoproteinemic serum protein level of 6.6 g/dL. His physical examination was unremarkable, except for emaciation (body mass index: 17.0 kg/m2).
Diagnostic PSG revealed a high baseline obstructive apnea-hypopnea index in the supine position (Table ), which was associated with remarkable respiratory efforts, and a PLM index of 32.2, which was associated with bilateral gross knee flexion accompanied by EEG arousals (PLM arousal index during sleep: 10.3). All his PLMs occurred during sleep. No tapping-like movements were observed when he lay on the bed with extended knees, which suggested that knee flexion induced the movements.
At-home continuous positive airway pressure (CPAP) treatment was initiated with an auto-titrating device. During a month-long period preceding the follow-up visit, the patient's average apnea-hypopnea index was 0.7, and his compliance was 100%, but he continued experiencing discomfort of the left leg, right foot tapping, and nonrestorative sleep.
The second diagnostic PSG under auto-titrated CPAP was obtained 2 months after the first PSG. Before the PSG, he received 4W-acuinjections of normal saline doses (0.25 mL each) supplemented with pentazocine (1 mg per dose) in both legs in the sitting position while tapping his right heel, and immediately afterward, he felt warmth to both legs with a pleasant sensation, and his left lower leg discomfort and involuntary right leg movements were completely relieved. During the PSG, his PLMs were almost completely suppressed except for one leg movement. The 4W-acuinjections caused no major change in percent sleep efficiency, but the patient reported remarkably restorative sleep upon waking up in the morning. |
pmc-6028366-1 | A 34-year-old Caucasian male had undergone intestinal transplantation originally more than 3 years ago because of chronic intestinal pseudo-obstruction due to familial visceral myopathy . The first intestinal transplant was lost due to volvulus 2 months post-transplant. Retransplantation was performed 18 months ago. Viremic cytomegalovirus (CMV) gastroenteritis was diagnosed 1 year post-transplant. Treatment with intravenous ganciclovir and later oral valganciclovir was successful, and CMV PCR remained negative in blood and intestinal biopsies during follow-up. The patient also suffered another volvulus of the colon, which was successfully corrected operatively. Mild grade 1 acute rejection in the colon occurred 2 months later; the small intestine was normal. The rejection resolved quickly with intravenous steroids; follow-up biopsies at 1 week were normal. After the rejection episode, there were nine follow-up endoscopies showing only mild segmental erythema and distorted mucosal vascular pattern on a confined area in the colon; we speculated the previous volvulus as a cause for these mild findings. In biopsy specimens, there were no signs of rejection or inflammation, and viral samples were negative.
Norovirus gastroenteritis was diagnosed 2 months after the rejection. The patient was admitted to the hospital due to dehydration, abdominal pain, and fever. Prior to this, the patient's family members had suffered symptoms of gastroenteritis, presumably of viral origin. In our patient, gastroenteritis symptoms with watery diarrhea persisted, and the patient needed repeated episodes of hospitalization due to dehydration. Norovirus PCR from the stools remained repeatedly positive, and the norovirus infection was considered a cause for the chronic diarrhea. Endoscopy findings were unchanged. Nearly 3 months after the initial norovirus infection diagnosis, treatment with oral immunoglobulin was started. An intravenous immunoglobulin solution (Privigen®) was given orally at a dose of 1250 mg (25 mg/kg body weight) four times daily for 2 days (altogether eight doses). The immunoglobulin solution did not bypass the gastric barrier. Tacrolimus trough levels during the preceding 4 months had been stable above 10 ng/L (range 11.5–18.3 ng/L), and the patient had received triple immunosuppression therapy with MPA 360 mg twice daily and methylprednisolone 6 mg daily.
Four days after the end of the immunoglobulin treatment, the patient was again admitted to hospital due to fever, increased diarrhea, and abdominal pain. Endoscopy via colostomy was performed, and severe biopsy-proven rejection grade 2–3 was diagnosed in the small-bowel and colon (Fig. and Fig. ). CMV and Epstein–Barr virus samples were negative. Tacrolimus trough level was 12.4 ng/L. Initial therapy was by high-dose intravenous methylprednisolone. However, signs of rejection persisted on repeat endoscopy, and finally, a 10-day course of intravenous antithymocyte globulin was started, whereby the acute rejection resolved both symptomatically and in graft biopsies (Fig. ). Donor-specific antibodies were negative. Follow-up endoscopies showed persisting signs of colitis and distal ileitis, but these finally resolved at 3 months after starting immunoglobulin therapy, and the patient has remained rejection-free now 10 months later.
The norovirus infection persisted, and the patient was started on nitazoxanide 500 mg twice daily, but without any clear clinical or virologic response. Bacterial, other viral, and parasitic samples were negative (Fig. ). |
pmc-6028367-1 | A 55-year-old male patient presented to our department with progressively worsening, right hypochondrium pain. He complained for abdominal distention and early satiety for the last 2 months. His history was significant for a one-year onset of mildly elevated arterial pressure, successfully managed with administration of low-dose amlodipine. Clinical examination revealed a voluminous palpable mass occupying the left quadrat of his abdomen. Abdominal ultrasound imaging showed a huge cystic mass posterior to the pancreas, compressing the stomach. Abdominal computer tomography (CT) confirmed the presence of a huge cystic retroperitoneal lesion, which measured 22 × 22 × 10 cm (Figure A,B). The lesion showed close intimacy to the posterior aspect of the pancreas. Endoscopic ultrasound fluid aspiration was negative for CA19-9 and amylase, whereas biopsy samples were inconclusive on the nature of the lesion. Albeit the fact that the lesion was not shown to arise from the left adrenal, 24-hour urine catecholamine levels were also examined and were within normal range. The patient's vital signs and blood CEA and CA19-9 were within normal range. The patient underwent complete excision of the cystic mass. Histology demonstrated the presence of pheochromocytoma, which arose from adrenal tissue and demonstrated immunohistopositivity to chromogranin and synaptophysin. Due to lesion size and microvascular invasion, it was categorized as malignant.
Due to their evolution in the retroperitoneal space, pheochromocytomas may grow significantly in size and remain asymptomatic for a long period of time. Moreover, contrary to solid, cystic pheochromocytomas may not present typical clinical symptomatology or urine values of catecholamine metabolites may be found within normal range. Such atypical presentation makes the preoperative diagnosis of giant retroperitoneal cystic lesions challenging. |
pmc-6028371-1 | A 26-year-old man who was referred to our hospital presented with a clinical history of exercise-related syncope. Coronary CT angiography revealed an anomalous aortic origin of the right coronary artery (RCA) from the left coronary ostium. The proximal portion of the RCA seemed to be coursing along the aortic vessel wall before running between the aorta and pulmonary artery (Figure A,B). CT-based fractional flow reserve (FFRCT) (HeartFlow, Redwood, CA, USA) in the RCA was 0.77 (ischemic cutoff ≤0.8), suggesting significant ischemia (Figure C,D). Coronary angiography suggested the presence of a slit-like ostium of the anomalous RCA (Figure E). Invasive FFR evaluation confirmed significant ischemia (Figure F). The treating physicians decided on surgical treatment.
An anomalous origin of the RCA from the left sinus of Valsalva is rarely seen congenital anatomy. Although the presentation is usually silent, clinical manifestations may include aborted sudden death, chest pain, arrhythmia, and/or exercise-induced presyncope or syncope. The FFRCT, derived from the usual data set from coronary CT angiography, was recently developed to evaluate functional ischemia of the coronary artery. In the present case, FFRCT revealed ischemia in an anomalous coronary artery, which was confirmed by the invasive FFR measurement. Thus, the FFRCT technique has potential for innovation in the assessment of anomalous coronary arteries. |
pmc-6028400-1 | We present the case of a 53-year-old female who transferred from an outside facility requiring a higher level of care, due to worsening pneumonia with possible abscess and the need for cardiothoracic surgery (CTS) consultation. Past medical history included previous breast cancer post-lumpectomy and radiotherapy, remote history of vulvar and rectal cancer post wide-debulking, chronic obstructive pulmonary disease, and ventilator-dependent respiratory failure with tracheostomy. Home medications included albuterol/ipratropium nebulizer, alprazolam, amlodipine, aripiprazole, budesonide/formoterol metered dose inhaler, citalopram, tamoxifen, tiotropium inhaler, trazodone, and oxycodone. She reported an allergy to nonsteroidal anti-inflammatory drugs. The patient initially presented to another facility complaining of fever, diarrhea, shortness of breath, and increasing oxygen demands. On examination, the patient was not in acute distress. All systems were negative except for diminished lung sounds with rhonchi bilaterally. A chest X-ray demonstrated left upper lobe pneumonia. Blood cultures were drawn, and a sample of tracheostomy secretions was sent for culture and sensitivities. She was initiated on vancomycin and piperacillin-tazobactam for treatment of healthcare-associated pneumonia. The patient reported a history of Clostridium difficile colitis and was started on oral vancomycin and IV metronidazole. On day 2, a bronchoscopy was performed with washings sent for culture. Both respiratory cultures grew MDRPA while blood cultures remained negative. The susceptibility profile is outlined in Table . Piperacillin-tazobactam was switched to meropenem at 2 g IV every 8 hours, and inhaled tobramycin was added. A repeat bronchoscopy was performed on day 12 due to mucus plugging and lack of clinical response. This culture grew persistent MDRPA, necessitating the addition of IV tobramycin on day 16. Inhaled tobramycin was switched to inhaled colistin on day 20. On day 23, tobramycin IV and metronidazole were discontinued and the meropenem dose was decreased.
On day 24, a 12-French chest tube was successfully placed into the left upper lobe abscess. Approximately 30 mL of purulent material was aspirated and sent for culture. Growth from this drainage continued to demonstrate MDRPA. One day after chest tube insertion, a computed tomography (CT) scan of the chest demonstrated significantly diminished fluid component of the left upper lobe abscess with drain positioned in the air-containing component; residual left upper lobe and left lingular pneumonia and pulmonary emphysema was also noted. The patient failed to improve and on day 28 ceftolozane-tazobactam was initiated at 1.5 g IV every 8 hours. A repeat chest CT scan on day 30 showed a decrease in the left upper gas-fluid collection, but persistent dense pneumonia of the left upper lung and a new smaller infiltrate in the left lower lobe.
Two days after the repeat chest CT, the patient was transferred to our facility for worsening pneumonia, requiring a higher level of care and CTS consultation. Abnormal clinical examination findings included diffusely diminished lung sounds, rales in the left lower lobe, a left pigtail chest tube drain, tachycardia with heart rate of 120 beats per minute, and tachypnea with a respiratory rate of 22 breaths per minute. The patient's chest tube was intact with a small amount of thick, white drainage, which was sent for culture, along with 2 sets of blood cultures. Ceftolozane-tazobactam 1.5 g IV every 8 hours was continued, and meropenem was stopped. The patient was initiated on tobramycin 280 mg (7 mg/kg) IV every 24 hours. CTS diagnosed the condition as a pulmonary abscess with bronchopulmonary fistula (BPF). The patient was deemed a poor surgical candidate, and continued medical management and drainage via chest tube was recommended. Repeat cultures from the pleural fluid drainage continued to grow MDRPA, while blood cultures remained negative. Susceptibility testing for ceftolozane-tazobactam was requested and performed using an investigational elipsometer (E)-strip. On day 36 overall (day 5 post-transfer), a repeat bronchoscopy was performed. Culture of the washings grew Acinetobacter baumaunii. Additionally, the results from the ceftolozane-tazobactam E-strip for Pseudomonas finalized, demonstrating an MIC of 12 mg/L (nonsusceptible). Chest CT on day 37 demonstrated mild interval increase in the air-fluid collection size, drain in place, persistent extensive left upper lobe pneumonia, and mild improvement in the lingula and left lung base. With no improvement and the growth of Acinetobacter, ceftolozane-tazobactam was discontinued on day 39, after 12 days total. Meropenem at 1.5 g (pediatric dosing of 40 mg/kg) IV every 8 hours and colistin 100 mg (2.5 mg/kg) IV every 12 hours were started. After 14 days of meropenem and colistin without improvement, all therapy was stopped and the patient was transitioned to comfort care and ultimately expired. |
pmc-6028404-1 | The patient is a 53-year-old male with a history of alcoholic cirrhosis, who presented with a one-day history of severe generalized muscle weakness and myalgias; he was unable to rise from a chair without assistance. His cirrhosis was diagnosed in October 2016 per clinical history and findings on Computed Tomography (CT). His disease was complicated by Grade 2 esophageal varices, ascites, and hepatic encephalopathy (HE). He also had one hospitalization approximately 1 month prior to admission for an upper gastrointestinal bleed (UGIB), requiring four variceal bands. He had no history of spontaneous bacterial peritonitis (SBP). On admission, his model for end-stage liver disease (MELD) score was 20; his Child-Pugh Score was 12, placing him in Class C. His last drink was 32 days prior to presentation.
On arrival he was afebrile, tachycardic, and mildly hypertensive, but appeared comfortable. Physical examination was remarkable for symmetrical proximal muscle tenderness and weakness - ⅘ in the upper extremities and ⅗ in the lower extremities. Reflexes were 1+ and symmetric; sensation was intact. Laboratory testing was significant for leukocytosis, as well as elevations in the creatinine, aspartate aminotransferase (AST), white blood cells (WBC), and creatine kinase (CK) (Table ). The patient was also found to have an elevated erythrocyte sedimentation rate (ESR) at 71 mm/h, C-reactive Protein-Quantitative (CRP-QT) at 2.7 mg/dL, and lactate 3.5 mmol/L. Chronic abnormalities in his hemoglobin, albumin, INR, bilirubin, and alkaline phosphatase were also present, although remained stable throughout admission. Urinalysis demonstrated large blood on the dipstick, but was likely due to myoglobin, as microscopy revealed only 0-5 RBCs per high-power field. The etiology of his rhabdomyolysis was not apparent: he denied seizures, trauma, increased exertion, prolonged immobilization, recent travel, or use of statins, supplements, alcohol, or illicit drugs.
He was treated with aggressive intravenous fluid resuscitation. Despite resolution of his acute kidney injury, clearing of his lactate, and initial improvement in his laboratory values, his CK, WBC, and AST plateaued and began to rise again on day four (Figure and Table ). With ongoing muscle injury and persistent weakness, other etiologies (including autoimmune, infectious, and malignant) were investigated. CT chest/abdomen/pelvis was negative for abscess or mass lesions; muscle biopsy of the right thigh showed no evidence of vasculitis or acquired inflammatory, necrotizing, or metabolic myopathy (Figure ). Anti-Jo-1 and anti-HMG-CoA reductase antibodies were both negative. Further medication review revealed he was recently started on rifaximin for hepatic encephalopathy prophylaxis. Rifaximin has been occasionally reported to cause rhabdomyolysis in patients with hepatic insufficiency. We subsequently held his rifaximin on day six and noted a marked downtrend of CK the next day (Figure and Table ). The CK continued to downtrend and his myoglobinuria resolved soon after. The patient’s strength continued to improve with therapy, and he was discharged on day 16 with a diagnosis of rifaximin-induced rhabdomyolysis. |
pmc-6028405-1 | A 59-year-old man presented with eight-week history of nausea, abdominal pain, and 20-lbs weight loss. Two years prior to the current presentation, the patient was diagnosed with a stage T1A nonsmall cell lung cancer of the right upper lobe (large cell carcinoma) and his initial staging Positron Emission Tomography and Computed Tomography (PET-CT) was negative except for the above-mentioned lesion. The patient refused surgery at the time and completed Stereotactic Body Radiation Therapy (SBRT). His serial six-month interval surveillance imaging has been negative.
With his prior history of cancer and the current presentation, a total body PET-CT was ordered. This showed thickening of the wall of the gastric fundus, a mass in the tail of the pancreas (both with increased radiotracer uptake), and a 1.1-cm filling defect within the splenic vein consistent with thrombus (Figure ). Upper endoscopy showed a 5-cm infiltrative and ulcerated mass with heaped-up margins and necrotic center located in the gastric fundus (Figure ). Gastric biopsies showed poorly differentiated carcinoma (positive TTF1 and cytokeratin AE1-3, negative CDX-2) (Figure ), suggestive of metachronous metastasis from a lung primary. Endoscopic ultrasound (EUS) was performed and showed a 26 mm × 23 mm hypoechoic round mass in the tail of the pancreas with local vascular involvement and splenic vein thrombus (Figure ). EUS-guided fine needle aspiration (FNA) and fine needle biopsy (FNB) of the mass was performed through the gastric lumen (away from the gastric tumor to avoid tumor contamination or seeding by the needle tract). This confirmed neuroendocrine carcinoma (positive synaptophysin and chromogranin, positive Ki-67 and CDX-2, negative TTF1) (Figure ). Findings were suggestive of synchronous primary pancreatic neuroendocrine carcinoma. Treatment options were discussed with the patient and his family. Patient opted for palliative care and received symptomatic treatment.
Metastasis of primary lung tumor to the stomach is infrequent and sporadic. The pathogenesis is thought to be related to the tumor cell spread via the hematogenous and lymphatic routes, but there is no specific data demonstrating a particular tropism for a segment of the gastrointestinal (GI) tract. Only 21 sporadic cases have been reported in the English literature and involved different malignant cell types: squamous cell carcinoma (10 cases), adenocarcinoma (6 cases), small cell carcinoma (2 cases), pleomorphic (2 cases), and large cell carcinoma (1 case). Symptomatic cases presented with epigastric pain, chronic anemia, signs of GI bleed (hematemesis, melena), and gastric perforations (in two cases). The definite role of PET-CT in the diagnosis of GI metastasis from lung cancer is still controversial because of the few cases and lack of enough clinical data. EUS-FNA in combination with immunohistochemistry is useful for diagnosing metastatic lesions and differentiating those from synchronous primary lesions., |
pmc-6028406-1 | The patient was a 65-year-old man histopathlogically diagnosed with cardiac sarcoidosis at the age of 35 years. The 12-lead electrocardiogram exhibited an intraventricular conduction disturbance and left superior axis. The left ventricle (LV) exhibited a progressive dilation with a contractile dysfunction (severe hypokinesis on the inferior and inferior and septum). He was implanted with a cardiac resynchronization therapy device with defibrillator capability. In spite of the administration of amiodarone 100 mg, sotalol 160 mg, carvedilol 7.5 mg, mexiletine 400 mg, enalapril 2.5 mg, and spironolactone 25 mg, the patient was admitted to our hospital due to repetitive drug-resistant VT episodes and decompensated heart failure. The LV exhibited dilation and contractile dysfunction with an LV ejection fraction of 18%. In addition to the amiodarone, sotalol, carvedilol, mexiletine, enalapril, and spironolactone, intensive treatment of a VT storm and decompensated heart failure was performed with lidocaine 40-100 mg/h and furosemide; however, the VTs still could not be controlled.
The clinical VT on the 12-lead electrocardiogram exhibited a right bundle branch block pattern and left superior axis (Figure ). The VT cycle length was 380 millisecond, with a widened QRS duration of 184 millisecond. RFA was performed to manage the VT storm.
Steerable catheters were inserted from the right femoral vein and placed in the right atrium and ventricle of interest. The LV endocardium was accessed using the trans-septal approach. Electroanatomical mapping was performed with EnSite (Abbott, Chicago, IL). A 3.5-mm open-irrigated ablation catheter (Therapy™ Cool Path™ Duo: Abbott) was used for the ablation and mapping. Bipolar voltage maps of the endocardium of the LV and right ventricle (RV) were constructed at baseline (pacing rhythm). Low voltage zones, defined as <1.5 mV, were mainly located on the interventricular septum (IVS) and postero-inferior wall of the LV. The clinical VT was induced and was hemodynamically stable. Entrainment mapping revealed that the VT had a reentrant mechanism. Activation mapping was performed; however, it could not depict the entire circuit, suggesting that a part of the circuit was intramural and/or epicardial. We performed RFA on the inferior and infero-septal walls of the LV and IVS from both the RV and LV endocardium, based on the activation and/or substrate maps, targeting the low voltage zones and/or abnormal electrograms such as those with fragmented and double potentials (Figure A). The procedural endpoint was the noninducibility of the clinical VTs. RF current was delivered for up to 60 seconds in the power-controlled mode with 30-45 watt and an irrigation rate of 17 mL/min.
We performed sequential RFA from the LV and RV; however, the VT did not terminate or slow. A SURF ablation on the inferior IVS from both the LV and RV endocardium was also performed. The ablation catheter used on the LV was a 3.5-mm open-irrigated ablation catheter (Therapy™ Cool Path™ Duo: Abbott), and that on the RV was a 4-mm nonirrigated ablation catheter (Therapy™ Thermocouple: Abbott). When performing the SURF ablation, two separate dispersive patches were used as the indifferent electrodes, with two separate generators in the power-control mode for the delivery of the SURF. RF current was delivered in the power-control mode starting at 10 watts, independently titrated up to 30 watts for each catheter with care taken to limit the temperature to <42°C for the irrigated catheter and <55°C for the nonirrigated catheter. The RF delivery was discontinued when the catheter tip impedance of either catheter dropped by more than 15 Ω as monitored from both RF generators. Figure B shows the position of the two ablation catheters when the SURF ablation was performed from both the RV and LV endocardium. We performed the SURF ablation at two sites on the IVS. The mean percentage of the R-wave reduction achieved by the SURF ablation was 67% on the LV endocardium and 86% on the RV endocardium. The VT was terminated and/or slowed during the RF application on the inferior wall of the LV and inferior IVS. The total application time of the RFA was 3502 seconds.
The clinical VT could not be induced at the end of the procedure. However, a VT with a slightly different QRS morphology emerged 2 days after the session and his heart failure worsened and became more serious due to VT storms. He developed pulseless electrical activity after that, and required intubation, sedation with propofol, percutaneous cardiopulmonary support, and intra-aortic balloon pumping. A second ablation session was performed 9 days after the first session. The VT was eliminated by RF applications on the infero-septal wall of the LV. No further VTs emerged after the RFA. The patient, however, died from deterioration of his heart failure 12 days after the procedure. A postmortem examination of the heart was performed.
Figure A shows a cross section of the ablation lesions on the IVS in a four chamber slice, where the ablation lesions from the SURF ablation were assessed. The heart was significantly enlarged and weighed 505 g. The ventricular septum was thin. The yellow arrow heads in Figure A indicate the ablation lesions. The black-colored areas were lesions with hemorrhaging caused by damage to small intramural coronary arteries and capillaries and the adjacent cloudy discolored areas were necrotic tissue caused by the RF energy. The ablation lesions were mainly located on the IVS and inferior wall of the LV. Figure B shows identical histologic sections to those ablation lesions on the IVS in Figure A. The original pathologic fibrosis resulting from the cardiac sarcoidosis extended diffusely onto the IVS. In Figure B, the area surrounded by the blue line was assumed to be the ablation lesions created from the LV endocardium, and the area surrounded by the yellow line was the lesions created from the RV endocardium. Those lesions were contiguous, creating a transmural ablation lesion on the IVS. There was, however, a little spared viable myocardial tissue that escaped the RF energy on the LV endocardial surface (area surrounded by the red dotted line) despite the deeper sites having been completely ablated.
There was no active epithelioid granuloma from the sarcoidosis observed in the autopsy. |
pmc-6028407-1 | In 2012, a 22-year-old edentulous female patient was referred to the Oral and Maxillofacial Surgery Department of Tehran University of Medical Sciences. She had severe class III malocclusion and facial deformity, which included nasal and mandibular deviation to the right. After taking a comprehensive medical and dental history, we noticed that the patient had hypodontia with several impacted teeth due to amelogenesis imperfecta (Figure ).
Intra-oral clinical examination revealed horizontal discrepancy of alveolar ridge, knife-edge mandibular alveolar ridge, uneven alveolar ridge, and a deep palate (Figure ).
Routine radiographic examinations consisting of panoramic radiography and lateral cephalometry were requested. The cephalogram exhibited anterior-posterior discrepancy of the jaw in the horizontal plane and a pseudo-long face.
Following consultation with a prosthodontist, cosmetic surgery was scheduled for the patient to correct her long face, mid-face deficiency, jaw deviation to the right, class III discrepancy, and alveolar ridge deficiency followed by dental implant placement and full mouth prosthetic rehabilitation. After consultation with an orthodontist, it was found that forced eruption of the impacted teeth was not possible; thus, the teeth were extracted under local anesthesia.
Primary impressions were made using irreversible hydrocolloid impression material (Kimica, Tokyo, Japan). Special trays were fabricated, and final impression was made by zinc oxide eugenol (Wuhan Xingzhengshun, Hubei, China). Then, the occlusal rims were made to record the inter-arch relationship, and the casts were mounted in a semi-adjustable articulator (Dentatus, New York, USA) in centric relation. The teeth were arranged in class III occlusion, and then they were coated with barium sulfate (Foshan Xinmei Chemical, Guangdong, China) to make them opaque for easy detection of the occlusal line for Epker cephalometric prediction tracing (Figure ).
The Epker prediction tracing was performed for preoperative assessments, which included analysis of the maxillary retrognathism, mandibular prognathism, and excess skeletal vertical growth. Sagittal split ramus osteotomy and LeFort I osteotomy were scheduled. According to the data obtained from the lateral cephalogram of the patient and clinical examinations (zygomatic regions, paranasal area, nasolabial, and gonial angles, SNA, SNB, and ANB angles), the surgeon planned a mandibular setback procedure by 7 mm and repositioning of the maxilla by 2 mm superiorly and 5 mm anteriorly on surgical casts. Then, the casts were mounted in this new position and the jaw relations were determined. Posterior teeth were arranged in new articulation and the final dentures were fabricated. The surgeon used these dentures for the edentulous patient as the final surgical splint. Mandibular cast and denture setback by 7 mm relative to its current position and an intermediate stent was fabricated using auto-polymerizing acrylic resin (Kulzer, Newbury, UK). Then, dentures were fabricated as splint and after polishing, several holes were drilled in the base of denture, and the arch bar was bonded to it. Circummandibular wires for the mandible and palatal screws were used to fix the splints to the corresponding jaws. The surgical procedure of the maxilla and mandible was performed using these splints (Figure ).
Alveolar ridge augmentation was performed by harvesting a graft from the iliac crest. The graft was placed upon a surgical stent and fixed to the external maxillary surfaces with a screw and plate.
After 2 weeks, temporary complete dentures were delivered to the patient. They were adjusted using tissue conditioner (Kerr, USA). Six months later, an impression was made and a radiographic stent was fabricated for implant placement. To determine the proper location for placement of implants, gutta-percha points (VDW, Munich, Germany) were placed at the center of desired teeth in ideal direction of implant, and the outer surfaces of the teeth were coated with barium sulfate (Foshan Xinmei Chemical, Guangdong, China) (Figure ).
The patient underwent cone beam computed tomography with stent to determine the proper site of implant placement (Figure ). Proper diagonal length and angle of 16 implants (Dentium, Implantium, Korea, Seoul), eight in each jaw, were determined by stent according to the available bone volume. Implants were inserted using a surgical stent. The temporary complete dentures of patient were relined and delivered to the patient. Three months later, the implants were uncovered, and healing abutments were tightened. Primary impression of the healing was made by alginate (Kimica, Tokyo, Japan). Primary cast was poured. After fabrication of special tray, final impression was made using the open tray technique following splinting of impression copings using polyvinyl siloxane (Zhengzhou Huaer, Henan, China). The final cast was fabricated. Impression verification jig was fabricated in a dental laboratory and was tried in patient's mouth to confirm the accuracy of impression. Next, the record base and wax rims were fabricated. The jaw relations were recorded by rims, and after that the teeth were arranged. The teeth set-up was checked in the mouth. A putty index was made from the arranged teeth and accordingly, proper abutment angle and gingival height were determined.
The three-part frames (Degubond, Dentsply sirona prosthetics, U.S.A, Pennsylvania) for the maxilla and mandible were fabricated. Frames were tried in the mouth, and the fit of frames was checked radiographically (Figure ). Porcelain crowns with A2 shade were fabricated. Implant-supported crowns were cemented with a temporary cement (Kerr, Toronto, Canada) (Figure ). The patient was fully satisfied with the results at the six-year follow-up. |
pmc-6028412-1 | A 38-year-old male underwent a tissue-matched renal allograft transplant for end-stage renal failure secondary to hypertension and primary antiphospholipid syndrome. Primary antiphospholipid syndrome was diagnosed 2 years prior to renal transplantation when he developed recurrent episodes of thrombosis of the arteriovenous fistula and neck veins, for which he was started on warfarin. Anticoagulation was optimized prior to surgery by withholding warfarin 5 days before surgery while bridging with heparin. During the early postoperative period (first postoperative week), he developed a peri-renal hematoma (ultrasonography 13 cm × 7 cm). Noncontrast computed tomography scan detected a homogenous fluid collection posterior to the transplanted kidney which extended superiorly up to the right subhepatic area and inferiorly into the pelvis, displacing the bladder to the left (Figure ). Anticoagulation was then withheld and he recovered over the next few days with normalization of serum creatinine and urine output. Prior to discharge, his urethral catheter and ureteric stent were removed and warfarin was restarted.
Three weeks after the surgery, he presented with reduced urine output and progressive abdominal distension associated with pain and fever. Ultrasound scan revealed a large perigraft collection. Resuscitation and urgent exploration revealed a viable graft with a large urinoma posterior to the kidney. A possible anastomotic leak was suspected and a passive external drain was placed to allow adequate drainage of urine and healing of the anastomotic site. However, the conservative approach failed and there was no reduction in the drain output. Therefore, surgical exploration and definitive reconstruction were planned.
Surgical exploration revealed an allograft vascular pedicle in the inferolateral aspect of the graft with a completely sloughed off allograft ureter (Figure ). Sloughed part of the allograft ureter was excised up to the pelviureteric junction where the graft renal pelvis appeared well-perfused and healthy. Free flow of urine from the graft was noted. Ipsilateral native ureter was divided close to the native renal pelvis and approximated to the graft extraperitoneally, posterior to the vas deferens. Allograft pelvis- native ureter ureteropyelostomy was performed over a 6 French double J stent connecting the native ureter and the allograft renal pelvis, essentially similar to the technique described for the Anderson and Hynes dismembered pyeloplasty (Figure ). Recovery following surgery was uneventful with no evidence of obstruction or allograft failure. Six months following surgery, he developed a perirenal abscess around the graft kidney, which was successfully drained. A 99 m-Technetium DTPA (diethylene-triamine-pentaacetate) renography was carried out 9 months after surgery, which showed normal uptake and excretion with no evidence of obstruction (Figure ). At 1 year following the reconstructive surgery, the patient had good urine output with a stable serum creatinine at 1.2 mg/dL. |
pmc-6028413-1 | The patient was a 3-year-old boy of Ecuadorian, English, and German ancestry with overall growth delay, failure to thrive, global developmental delays, sensory feeding issues, ostium secundum-type atrial septal defect, kyphoscoliosis, 2-3 toe syndactyly, bilateral cryptorchidism, phimosis, hypotonia, dysmorphic features, and chronic constipation. Prenatal course was complicated by intrauterine growth retardation (IUGR) for which an amniocentesis was performed and demonstrated mosaic trisomy 20 by karyotyping. He was born at 34 weeks with a weight of 2 pounds 4 ounces and a length of 14 inches. Follow-up postnatal karyotype and chromosome microarray analyses (CMA) were normal, with no copy number abnormalities or large regions of homozygosity (ROH) identified. Additional features included microcephaly, midface hypoplasia, delicate facies, hypotelorism, epicanthal folds, low set ears, small nose, crowded gums (narrow alveolar arches), thin lips, small mouth, bilateral hockey-stick creases, and broad short neck. He had abnormal strength, mild joint limitation, hunched posture, and wide-based, irregular gait. His features were thought to resemble his father who was 5′7″ with a history of constitutional delay and 2-3 toe syndactyly. At the age of 16 years, the father was 4′8″ but then had a growth spurt in high school. The parents reported an early miscarriage. Maternal family history was noncontributory. Consanguinity was not reported. |
pmc-6028417-1 | A 70-year-old man with a 50-pack-year smoking history was suspected to have lung cancer and underwent pulmonary resection of the right lower lobe in December 2014. He was diagnosed with PPC (Figure A,B; EGFR/ALK-mutation negative) and pT2aN0M0 Stage IB (Union for International Cancer Control, UICC 7th edition) disease. Expression of programmed death ligand 1 (PD-L1) was detected in 80% of the resected lung using an anti-PD-L1 SP142 antibody (Figure C). Although the patient had received adjuvant chemotherapy with tegafur/uracil, bilateral adrenal gland metastasis was detected in April 2015. We administered several chemotherapy regimens: carboplatin and paclitaxel (4 cycles); pemetrexed (9 cycles); vinorelbine (8 cycles); and docetaxel (2 cycles). Right adrenal metastasis increased and compressed the inferior vena cava, which caused leg swelling. At that time, CT revealed pleural effusion and pulmonary metastasis (Figure A). We administered nivolumab therapy as the fifth-line therapy in October 2016. After 6 cycles of nivolumab therapy, the right adrenal gland metastasis was reduced, and his swollen legs and performance status improved; however, the pleural effusion and pulmonary metastasis were exacerbated (Figure B). The cytological analysis revealed that malignant cells were not detected and lymphocytes were predominant in pleural effusion. The left ventricular ejection fraction measured by echocardiography was 70% and the brain natriuretic peptide was 9.2 ng/mL (normal range < 18.4 ng/mL). The inferior vena cava (IVC) diameter was 20 × 8 mm and the respiratory variation in the IVC was more than 50%. Malignant pleural effusion and heart failure were unlikely. After 13 cycles, these lesions were improved by continuous nivolumab therapy (Figure C). Moreover, serum cytokeratin 19 fragment (CYFRA 21-1) levels were 40.7 ng/dL (normal range <3.5 ng/mL) before the initiation of nivolumab therapy and they decreased to 8.7 ng/dL after 6 cycles and to 4.1 ng/dL after 13 cycles. Serum carcinoembryonic antigen (CEA) levels were 2.9 ng/mL (normal range <5.0 ng/mL) before the initiation, 2.6 ng/mL after 6 cycles, and 3.9 ng/mL after 13 cycles. We diagnosed the patient with pseudoprogression of PPC. Follow-up is ongoing to date (June 2017), and he has achieved a partial response with continuous nivolumab therapy without exacerbation or adverse effects. |
pmc-6028419-1 | A 48-year-old female patient sought medical attention due to increased abdominal size, daily fever, significant weight loss, and cholestatic jaundice initiated about 2 years previously. The patient also reported dyspnea under moderate stress. Physical examination showed hepatomegaly and erythematous plaques on the face (Figure A) and left inferior limb. Laboratory evaluation demonstrated elevated hepatic enzymes, hyperbilirubinemia, anemia, and polyclonal hypergammaglobulinemia. Abdominal magnetic resonance imaging (MRI) revealed hepatosplenomegaly with hypointense nodules, as well as lymph node enlargement at the splenic hilum (Figure B). Chest computed tomography demonstrated pulmonary nodules predominating along the bronchovascular bundles, with bilateral hilar enlargement (Figure C,D). Histologic samples from hepatic and cutaneous biopsies exhibited granulomas with epithelioid cells and multinucleated giant cells. The final diagnosis was sarcoidosis.
Sarcoidosis is an immune-mediated systemic inflammatory disease of unknown etiology, characterized by noncaseating epithelioid-cell granulomas. Sarcoidosis may affect virtually any organ system, although 90% of patients present with pulmonary involvement., ,
Extrapulmonary disease is reported in 30% of patients, with the liver and spleen being the most frequently affected abdominal organs. Homogeneous hepatomegaly often associated with splenomegaly and enlarged lymph nodes is the typical imaging feature of abdominal sarcoidosis., Multiple nodules may also be found. Cutaneous lesions occur in about 20%-30% of patients and may assume numerous morphologic presentations. In conclusion, the clinical course of sarcoidosis is highly variable. Thus, knowledge of the clinical and radiologic features of the disease is imperative for its diagnosis and management. |
pmc-6028421-1 | We report a case of 34-year-old woman in her 11th week of pregnancy with recurrent symptomatic refractory SVT who underwent a successful fluoroless ablation.
Her electrocardiogram (Figure ) demonstrated a long RP SVT with a heart rate of 180 beats per minute. She failed vagal maneuvers and adenosine administration and was started on a Diltiazem and Esmolol drip. Although her rate decreased to 120 beats per minute she became hypotensive. A cardioversion with anesthesia was transiently successful; however, she had shortly a recurrence of her tachycardia. A repeat cardioversion with an amiodarone bolus was also unsuccessful. With sotalol the SVT was no longer incessant, but the patient continued to show frequent long periods of SVT or salvos of premature atrial contractions (PACs). Given her continued instability, she was referred for an electrophysiology study and ablation.
To minimize the radiation risk to the fetus we attempted a fluoroless ablation. Three dimensional (3D) electro-anatomical mapping (CARTO 3 Version 4 software, Biosense Webster, Irwindale, California) was created with an irrigated contact force sensing catheter (Figure A). With the right atrial (RA) geometry including the coronary sinus delineated, a steerable decapolar catheter was placed in the coronary sinus (CS) using our map as a reference. Although with sedation the patient was not in tachycardia, she was having frequent salvos of PACs (Figure B) with proximal to distal activation on the CS tracings. The differential for the origin of the tachycardia was thought to be from the right-sided pulmonary veins, superior vena cava (SVC) tachycardia or crista terminalis (CT). The patient therefore had another decapolar catheter placed along the CT with its most distal pole in the SVC. Isoproterenol of 2 mcg/min was administered; however, we could still not induce the tachycardia. Activation mapping of these PACs consistently demonstrated earliest activity on the anterior-superior portion of the CT. At this location, we had poor contact force and therefore the short sheath was exchanged for a Schwartz Right 0 (SR0) sheath. Prior to ablation high output pacing was performed and demonstrated no phrenic nerve capture. With the sheath, we could obtain a contact force between 10-20 g and ablation at 30-35 Watts resulted in immediate termination of the PACs (Figure C). The Holter at the end of the case demonstrated no further PACs (Figure ). |
pmc-6028424-1 | A 49-year-old male presented to hospital in May 1998 because of spontaneous bruising and mucosal bleeding. His platelet count was 2 × 109/L. The other blood counts were normal, and no other laboratory abnormalities were noted. He had a history of alopecia totalis, but no other concomitant illness and no family history of blood disorders. He was treated with prednisone (100 mg daily) and his platelet count improved, but when the dose of prednisone was gradually reduced and stopped, the thrombocytopenia returned. He subsequently underwent laparoscopic splenectomy in December 1998, which resulted in a positive platelet count response that lasted 4 years. In April 2003, the thrombocytopenia relapsed and after another course of prednisone, platelet count levels displayed a pronounced cyclical pattern of thrombocytopenia alternating with thrombocytosis (Figure A), with platelet count fluctuating with a statistically significant (P ≤ 10−22) period of 39 days (Figure B) from nadir values of less than 5 × 109/L to peak values of greater than 900 × 109/L. Statistically significant (P ≤ .001, Figure D) oscillations of exactly the same period in neutrophil counts (Figure C) were also found, but the neutrophil nadir never dropped below the normal range.
Cyclic thrombocytopenia persisted for over 10 years despite treatment with corticosteroids, intravenous immunoglobulin, danazol, pulse dexamethasone, and rituximab (4 weekly doses 375 mg/m2). TPO levels were measured serially for a period of 6 weeks (Figure E): TPO levels were undetectable during periods of extreme thrombocytosis and increased when platelet counts were low.
Treatment with the oral TPO receptor agonist eltrombopag was started and timed with anticipated periods of thrombocytopenia; specifically, treatment was withheld during anticipated periods of escalating platelet counts and restarted when platelet count was anticipated to drop below 100 × 109/L. The patient received 50 mg of eltrombopag daily from 30 November to 6 December 2010, 2 January to 15 January 2011, and 22 February to 14 March 2011. This resulted in extreme thrombocytosis and did not alter the cycle pattern or period (Figure F, periods of treatment within the double arrows); thus, eltrombopag was discontinued thereafter. |
pmc-6028424-2 | A 53-year-old male presented with severe thrombocytopenia in 1999. Splenectomy was carried out in October 1999, but he continued to have severe thrombocytopenia and required frequent doses of intravenous immunoglobulin (IVIG) and corticosteroids. Two years later, he was started on a combination of immunosuppressant medications, which included azathioprine, cyclosporine, and mycophenolate for presumed ITP. In April 2003, the platelet count levels began to oscillate periodically (Figure A) with a statistically significant (P ≤ .05) period of 23 days (Figure B) from a nadir of <10 × 109/L and a peak of 300-400 × 109/L. During episodes of severe thrombocytopenia, he frequently had bleeding with oral mucosal blood blisters. Treatment with danazol was added but had no effect. The patient's neutrophil count was normal, and despite apparent fluctuations (Figure C), statistically significant cyclicity in the neutrophil count was not detected (Figure D).
Six years later, eltrombopag was started at a dosage of 50 mg per day. This resulted in extreme thrombocytosis (peak platelet counts 1361 × 109/L) and eltrombopag and all immunosuppressant medications were stopped (Figure E, period of treatment within the double arrows). Following that, the patient experienced a period of severe thrombocytopenia (platelets <10 × 109/L) for approximately 4 weeks. Subsequently, eltrombopag was slowly restarted and immunosuppressant medications were re-introduced. The cyclical thrombocytopenia became less severe with higher nadir platelet values and 4 years later the cyclical pattern resolved. At the last follow-up in May 2015, the patient's medications were eltrombopag 75 mg daily, and low doses of azathioprine and mycophenolate. |
pmc-6028432-1 | An 85-year-old man with coronary artery disease (CAD), prior coronary artery bypass graft (CABG) surgery and permanent atrial fibrillation (AF) was admitted with recurrent, unexplained syncope. His baseline electrocardiogram (ECG) and telemetry monitoring showed AF with a slow ventricular rate as well as right bundle branch block (RBBB) and left anterior fascicular block (LAFB; Figure A). The QRS duration was 156 milliseconds. Due to concern over paroxysmal AV block or ventricular arrhythmia as the cause of his syncope, electrophysiology (EP) study with possible device implantation was recommended. An octapolar catheter (Biosense Webster, Diamond Bar, CA) was positioned near the His-bundle location. Intracardiac electrograms (EGMs) revealed infra-Hisian block at baseline, and there were no inducible ventricular arrhythmias during the EP study (Figure A). Pacing from the His catheter in this location resulted in QRS narrowing, so the decision was made to implant a permanent His-bundle (PHB) pacemaker. The octapolar catheter was left in the His-bundle position as a fluoroscopic marker for PHB lead placement.
A fixed-curve delivery sheath (His C315, Medtronic, Inc.) was used to direct the PHB lead (Model 3830, Medtronic, Inc.) toward the membranous septum. The PHB lead was connected to the EP laboratory recording system (Cardiolab, GE), and a His potential was recorded from the PHB lead (Figure A). High-output unipolar pacing from the PHB lead at this location resulted in a narrow QRS complex (104 milliseconds) with resolution of the RBBB and LAFB (Figure B). However, despite resolution of the conduction abnormalities, intracardiac EGMs on the octapolar catheter revealed that the recorded His-bundle potential was not captured during PHB lead pacing. The octapolar catheter was advanced beyond the PHB lead tip to ensure there was not capture of the distal His bundle (or right bundle branch; Figure A). Recordings from the octapolar catheter in this location revealed antegrade activation of the His bundle, again without capture of this electrogram during pacing (Figure B). Pacing at lower outputs resulted in non-selective His capture with a His threshold of 1.75 V @ 1.0 milliseconds and an RV septal threshold of 0.75 V @ 1.0 milliseconds. The thresholds remained stable, and the patient was discharged the next morning. What is the mechanism of QRS narrowing in this patient with advanced conduction disease? |
pmc-6028442-1 | A 73-year-old overweight male patient complained about mild right subcostal abdominal pain and deteriorating dyspnea upon exertion. The patient had previously undergone multiple thorax X-rays and was diagnosed with an asymptomatic elevation of his right hemidiaphragm (Figure A). A new thorax X-ray showed persistent right-sided hemidiaphragmatic elevation (Figure B). Physical examination revealed decreased to eliminated right lung base breath sounds. Percussion in this area was evident for a solid mass. Lung or subdiaphragmatic liver tumor was part of the differential diagnosis. Abdominal ultrasound and cross-sectional imaging (thorax-CT, abdominal MRI) revealed a giant subdiaphragmatic hepatic lesion (16 × 12 × 9 cm), centrally located in the liver (segments IVa, VIII, VII, and partially IVb and V) (Figures C-E). Serological examinations were negative for viral hepatitis. Alcohol intake was referred to as light to moderate. The suspicion of hepatocellular adenoma was raised. The patient was admitted to our hospital and underwent an atypical central hepatic resection (Figures F,G). His postoperative course was uneventful and he was discharged on 8th postoperative day. Histological examination showed a well-differentiated HCC, (pT1) arising from nonalcoholic steatohepatitis, resected in clear margin (R0). The patient remains in excellent general condition and recurrence-free 38 months postoperatively.
Progressive dyspnea can be a frequent finding in geriatric patients due to several causes. On the other hand, dyspnea as a primary symptom due to hemidiaphragm elevation in the context of an underlying liver tumor is extremely rare. Moreover, symptomatic elevation of the right hemidiaphragm should always raise suspicion of a silent hepatic tumor. |
pmc-6028443-1 | Our case was a 28-year-old male heavy smoker with morbid obesity (initial weight = 150 kg, height = 180 cm BMI = 46 kg/m2) that was operated with a LSG at another institution with a stable postoperative course. He reported chronic dysphagia and vomiting despite normal postop imaging (upper GI series and CT scan). Patient has lost the foreseen weight at 6 months (50 kg, BMI = 30.86 kg/m2, %EWL = 72.5%), but he presented to our institution 8 months later with a left pleuritic chest pain, nonradiating in nature associated with left shoulder pain, dyspnea, fever, chills, and decrease food intake (he stopped eating well 2 weeks prior to presentation because of described odynophagia and took multiple doses of IV NSAIDS). Upon admission, patient was hypotensive with a deteriorating general status (anxious, nadir GCS was 11, hypotensive, tachycardic) and a bad respiratory status (dyspnea, tachypnea, crackles on physical exam specially in the left side, with decrease left sided air entry). A chest x-ray showed a left massive pleural effusion with left lower lobe consolidation (effusion + pneumonia) (Fig. ). In an effort to explain the cause of the effusion, a CT scan chest, abdomen and pelvis with IV and oral contrast, showed a proximal stomach (gastro-esophageal junction) staple line fistula that was draining to what was first described as a left upper quadrant abscess later found to be a GC fistula causing a left pleural effusion (reactional effusion) (Figs. and ). He had a chest tube placed immediately that drained nonpurulent sero-sanguinous liquid of which one set of culture was taken. He was then started on empiric antibiotics, ceftriaxone, and levofloxacin, after cultures were taken and the patient was kept NPO. Four days later, chest tube was removed, and conservative management was continued. Total parenteral nutrition was started because the patient was malnourished, with low serum albumin, low iron, and evident muscular wasting (although he maintained a BMI of 26). Results of new cultures were out and showed no growth. Patient's antibiotics were switched to piperacillin/tazobactam and fluconazole. He was scheduled for a salvage surgery with a laparoscopic esophagogastrectomy with a Roux-en-Y esophagojejunal reconstruction when his nutritional status was adequate enough for the procedure, and after resolution of his infection. Ten days after, a repeat CT scan was done that showed a smaller residual left pleural effusion plus enhancement of the visceral and peritoneal pleura, and persistence of the gastro-colic fistula (Fig. ). GP fistula was excluded and GC fistula was confirmed. Patient was discharged home with a naso-jejunal tube (placed 1 day before discharge) for enteral feeding with high protein shakes (1500 mL Fresubin HP and 10 scoops of Protiphar/day to compensate for his daily caloric needs of 2400 kcal per day) and was kept on PO antibiotics (co-amoxiclav). A total of 14 days of IV antibiotics and another 2 weeks of PO antibiotics were taken. Upon many outpatients’ consultations, the patient family was concerned with the possible risks and benefits of the reoperation that was thoroughly explained to them and to the patient with multiple counseling sessions. They opted to continue conservative treatment (antibiotics + naso-jejunal enteral nutrition) in an attempt for the fistula to resolve without surgery because they feared the possible outcomes. The patient was carefully monitored over the course of 8 weeks with serial CT scans and outpatient visits, and finally on the last CT scan, the GC fistula had completely resolved (Fig. ), with no evidence of pleural effusion and the patient was started on a progressive oral diet after removal of the Naso-Jejunal tube. On future follow-ups, the patient seemed to do well, with adequate nutrition and good quality of life. |
pmc-6028797-1 | A 37-year-old man (height, 170 cm; weight, 96.7 kg) was transported to our Poison Center 12 h after ingesting 500 mL of a fuel alcohol product containing 70% MeOH and 30% EtOH in a suicide attempt. On arrival, his vital signs were: Glasgow Coma Scale, E3V4M6; heart rate, 88 b.p.m.; blood pressure, 158/117 mmHg; respiration rate, 15 breaths/min; SpO2, 98% (room air); and body temperature, 36.2°C. He had no remarkable medical history and did not take medication. Arterial blood gas findings were: pH 7.344; PaCO2, 31.7 mmHg; PaO2, 102 mmHg; , 17.2 mmol/L; BE, −8.5 mmol/L. Plasma osmolality was 359 mOsm/kg, the osmolal gap (OG) was 75.8 mOsm/kg, and the anion gap was 13.8 mOsm/kg. Other blood laboratory findings were unremarkable.
We hypothesized that the patient had metabolized most of the EtOH because EtOH has a much higher affinity for alcohol dehydrogenase than MeOH and 12 h had already passed since ingestion of the product. The estimated serum concentration of MeOH (eMeOH) was calculated by 75.8 (OG) × 3.2 (molecular weight/10) to be 242.6 mg/dL. Given the diagnosis of lethal MeOH poisoning, repeated doses of fomepizole, an alcohol dehydrogenase inhibitor, were given i.v. and hemodialysis (HD) was intermittently carried out twice for 4 h each. After the first round of HD, OG and eMeOH decreased to 23.7 mOsm/kg and 75.8 mg/dL, respectively. During the second round of HD, OG and eMeOH decreased from 11.1 mOsm/kg and 35.5 mg/dL to 1.9 mOsm/kg and 6.0 mg/dL, respectively. As the patient was coherent and did not develop any serious signs or symptoms due to toxic metabolites of MeOH (e.g., vision abnormality), he was discharged on hospital day 4.
Serum samples were stored at −80°C. Serum concentrations of MeOH and EtOH were measured by headspace gas chromatography/mass spectrometry (HS-GC/MS) (GCMS-QP2020; Shimadzu, Kyoto, Japan). Sample injections into GC/MS were carried out using an HS sampler (HS-20; Shimadzu) at 50°C for 60 min. The GC/MS analysis conditions were: column oven temperature, 50°C; and column flow rate, 2.43 mL/min. AQUATIC-2 (0.25 mm I.D. × 60 m, df = 1.4 μm) (GL Sciences, Tokyo, Japan) was used for the separation column. Standard solutions containing 50–5,000 μg/mL of MeOH, 0.1–10 μg/mL of EtOH, and acetonitrile as an internal standard substance, were prepared, and a calibration curve was drawn by the internal standard method. Formic acid analysis was not possible due to the limited amount of sample. The MeOH, EtOH, and acetonitrile used for the analysis were purchased from Wako Pure Chemical Industries (Osaka, Japan). |
pmc-6029048-1 | A 60-year-old man was diagnosed with nuclear cataract in his right eye about 15 years after myopic LASIK surgery. His corrected distance visual acuity (CDVA) of the right eye was 0.52 logMAR with the refraction of − 4.50/− 0.75*29. He asked for a FLACS and desired spectacle independence after the IOL implantation. Corneal topography (Pentacam, Oculus Optikgerate GmbH, Wetzlar, Germany) showed a uniform, well-centered corneal flap (Fig. ), with a total corneal astigmatism of 0.9D, and a corneal irregular astigmatism of 0.115 μm. Besides, the 6 mm zone corneal spherical aberration (SA) was 0.392 μm while the angle kappa was 0.15. After a series of thorough assessments, we decided to implant a multifocal IOL with negative SA. For IOL power calculations, the standard IOLMaster (Carl Zeiss Meditec,Jena, Germany) biometry was performed and the Haigis-L formula was chosen to determine an IOL power of +23D for emmetropia. A steep merdian corneal incision was designed at 140 degree according to the Pentacam results.
The LenSx laser system (LenSx Laser; Alcon Laboratories, Inc., Fort Worth,TX, USA) was used to perform the surgery. After the patient’s eye was properly docked to the system, the arc cuts of the primary and side port incision were adjusted towards the limbus, anterior to the conjunctival vascular arcades, under the guided of the LenSx real-time imaging system. A 2.0 mm primary corneal incision (Fig. ), a 1.0 mm side port incision and a 5.0 mm capsulotomy were created by the laser. Nuclear prefragmention was performed to obtain 6 pieces in a cross pattern (Fig. ). Then phacoemulsification was proceeded in a standard stop-and-chop manner with the Stellaris system (Bausch + Lomb Laboratories, Rochester, NY, USA), and an AT Lisa tri 839MP IOL (Carl Zeiss Meditec AG) was implanted right afterwards. All surgical procedures were uneventful. The patient was instructed to apply topical dexamethasone tobramycin for 2 weeks and pranoprofen for 1 month postoperatively.
Anterior segment optical coherence tomography (AS-OCT, Carl Zeiss Meditec) showed a smooth corneal flap 1 week after FLACS (Fig. ). The distance from the external wound opening to the corneal flap edge was 0.15 mm. At 3 months postoperatively, the IOL was well centered in the capsule (Fig. ). Pentacam showed a uniform corneal flap (Fig. ) with slightly decreased total corneal astigmatism and corneal SA (Table ). Uncorrected visual acuitis were 0.00 LogMAR for distance, 0.10 LogMAR for intermediate at 80 cm, 0.10 LogMAR for near at 40 cm. The defocus curve (Fig. ) showed an optimal visual acuity at -3D apart from 0D, but maintained a functional range of visual acuity across from 0D to − 3.5D with visual acuity no less than 0.22 logMAR. Results of ocular aberrations (OPD Scan, Nidek Co., Ltd.) for 5 mm diameter pupils showed 0.831um of high order aberration (HOA), 0.648um of coma, 0.327um of trefoil, 0.119um of tetrafoil, and 0.311um of SA. Contrast sensitivity (CS, CSV-1000, Vector Vision, Greenville, OH) at 4 spatial frequencies (A: 3 cpd, B: 6 cpd, C:12 cpd and D:18 cpd) under both mesopic (3 cd/m2) and photopic (85 cd/m2) conditions were at a relatively low level within the normal range (Fig. ). Despite a mild halo, the patient was very satisfied with his vision. |
pmc-6029059-1 | A 59-year-old and overweight man (weight = 87 kg, BMI = 29.75) who suffered from a sleep apnea syndrome, was diagnosed with a stage III mantle cell lymphoma in December 2014. On admission, he presented systemic lymphadenopathy without any bone marrow involvement. Laboratory tests showed normal liver enzymes levels as well as negative hepatitis B and C serological profiles.
An oxaliplatin-based polychemotherapy followed by high-dose therapy and autologous stem cell transplantation was proposed. First-line chemotherapy with four cycles of R-DHAX regimen, including rituximab, dexamethasone, cytarabine and oxaliplatin was administered. After three courses, PET-CT (positron emission tomography) response assessment indicated a complete metabolic response. The patient then received conditioning regimen with BEAM 400, consisting of bicnu (300 mg/m2) for 1 day, etoposide (400 mg/m2) combined to cytarabine (400 mg/m2) for 4 days and melphalan (140 mg/m2) for 1 day prior to autologous HSCT. Anti-infective prophylaxis included valacyclovir and fluconazole, starting on Day −7. On March 16th, 2015 (Day 0), 9.8 × 106 cells CD34+/kg were infused. During this procedure, laboratory data did not display any abnormality, especially hepatic enzymes levels that were within the normal range. Despite antimicrobial therapy with Piperacillin–Tazobactam, the patient had persistent fever over the ensuing 72 h, requiring an empiric antifungal treatment with Voriconazole. No signs of invasive aspergillosis were detected (normal CT-scan) and aspergillus antigenemia were negative. Voriconazole was then replaced by Caspofungin on Day +6. On Day +8, oligoanuria was observed and physical examination revealed hepatomegaly, fluid retention, ascites and weight gain < 5% (i.e. 90 kg, +2 kg/48 h). Additionally, thrombocytopenia refractory to platelet transfusion was noted. On Day +9, the serum transaminase concentration increased in an explosive manner from 75 to 2914 UI/L in the morning and 5046 UI/L in the evening for aspartate aminotransferase (AST) and from 45 to 1216 UI/L for alanine aminotransferase (ALT). Similarly, the bilirubin level had reached 67 µmol/L (N < 21) accompanied with elevated creatinine level shifting from normal value to 230 µmol/L within 24 h (Fig. ). Alkaline phosphatase levels were initially normal and progressively increased along with SOS/VOD syndrome (2× ULN). The patient developed coagulation disorders as revealed by a progressive increase of INR whereas the Factor V remained normal (Fig. ). An elevated level of plasminogen activator inhibitor (PAI-1) was also noted with a value of 51 UA/mL (N < 16). An abdominal ultrasound was performed and confirmed hepatomegaly, ascites and decreased velocity in the portal venous flow. The subject whose weight increased more than 5% (i.e. 92 kg) was therefore diagnosed with hepatic VOD and was admitted to the Intensive Care unit. A treatment with Defibrotide at a dose of 25 mg/kg/day was immediately initiated.
Because of the atypical major increase in transaminases levels, a transvenous liver biopsy was performed on Day +10 and showed a patchy perivenular sinusoidal dilatation and congestion with hepatocyte plate disruption (Fig. ). A second abdominal ultrasound further supported the diagnosis of SOS/VOD with a worsening of doppler parameters, then harboring a reversed hepatic venous flow. Moreover, differential diagnoses such as fulminant viral hepatitis (hepatitis A, B, C and E, herpes simplex virus, cytomegalovirus, Epstein–Barr virus) were excluded. Despite symptomatic measures along with the maintenance of an adequate fluid balance and ascites removal with albumin infusion, renal failure could not be controlled. Because of anuria, hemodialysis was thus implemented on Day +9.
Neutrophils recovery was achieved on Day +11 and liver dysfunction gradually improved from Day +13 to Day +15 with decreased transaminases levels ([AST] 408 UI/L; [ALT] 494 UI/L) (Fig. ). Although his overall condition was progressively recovering, the patient presented a sudden hemodynamic instability with an acute respiratory distress syndrome requiring mechanic ventilation, on Day +16. A fulminant liver failure with uncontrolled lactic acidosis was observed. An abdominal CT scan was performed and showed an acute mesenteric ischemia with hepatic and renal ischemic injury. The patient died a few hours later of a multi-organ-system failure. |
pmc-6029076-1 | A 46-year-old Caucasian male was assigned to tolvaptan treatment as part of the TEMPO 3:4 trial in 2008. ADPKD had been diagnosed by ultrasound in 1998, which was performed because of hypertension and a positive family history for ADPKD. DNA analysis later showed a PKD2 mutation. In 2008, serum creatinine level was 94 μmol/L, with an eGFR of 83 mL/min/1.73m2 as calculated by the CKD-EPI formula []. Total kidney volume (TKV) was 2351 mL, and height adjusted TKV 1292 mL/m, corresponding to MAYO risk class 1D []. Urine showed microalbuminuria (albumin: creatinine ratio 4.75 g/mmol). Pre-tolvaptan, his 24-h urine volume was 1300 mL.
In that same year, tolvaptan was initiated and uptitrated to the maximum dose of 120 mg per day (90/30 mg) within three weeks. After completion of the TEMPO 3:4 trial, tolvaptan was stopped for one month. Thereafter tolvaptan was re-started as part of a compassionate use program. In 2015 this patient developed hypertension despite use of an angiotensin II receptor blocker (losartan 100 mg q.d.) and a beta-blocker (metoprolol 100 mg b.i.d.). Previously an alpha-blocker and a calcium antagonist had led to intolerable side-effects. Therefore HCT was started at a dose of 12.5 mg q.d. that was well-tolerated, and was later increased to 25 mg q.d.
Urinary volumes before and during tolvaptan treatment are shown in Fig. . In 2011, this patient collected 24-h urine once during the month in which tolvaptan was temporarily stopped. At that time urine volume was 1280 mL and urine osmolality 632 mOsm/kg. Mean 24-h urine volume (based on five measurements) on tolvaptan before HCT initiation was 4867 mL, mean urine osmolality was 212 mOsm/kg (range 164–250 mOsm/kg). After initiation of HCT (12.5 mg q.d.) 24-h urine production declined to 2878 mL, while urine osmolality increased to 290 mOsm/kg. After the increase of HCT to 25 mg q.d. the last 24-h urine collection measured 2699 mL and 280 mOsm/kg. Mean 24-h urine volume had declined during HCT co-treatment by 2078 mL (43%).
24-h creatinine excretion was used to verify whether urine collections were complete, assuming unchanged muscle mass over time creatinine excretion should be similar between urine collections. Mean 24-h creatinine excretion before start of HCT was 18.1 mmol/24 h, and after start of HCT 16.7 mmol/24 h, indicating no difference in urine collected.
During the nine-year treatment period, serum electrolytes were measured 37 times and stayed within the normal range during the whole period. These electrolytes include potassium (range 3.9–4.6 mmol/L), sodium (range 136–144 mmol/L) and calcium (range 2.34–2.57 mmol/L). There were no differences in average electrolyte concentration between the period with tolvaptan monotherapy and the period with tolvaptan-HCT combination therapy.
eGFR declined from 83 mL/min/1.73m2 in 2008 to 57 mL/min/1.73m2 in 2017 (Fig. ). While on tolvaptan monotherapy the slope of eGFR decline was − 1.35 mL/min/1.73m2 per year, whereas this was − 3.97 mL/minute/1.73m2 per year while on tolvaptan-HCT combination therapy.
Copeptin, a surrogate marker of vasopressin [], was measured a total of five times, all in a fasting state around the same time in the morning. In the three years on tolvaptan monotherapy it was measured twice, with values of 24.4 and 20.5 pmol/L. In the month the patient temporarily stopped using tolvaptan, copeptin dropped to 11.1 pmol/L. Thereafter, tolvaptan was reinitiated and copeptin increased to 23.3 pmol/L. Copeptin was highest during tolvaptan-HCT combination therapy: 29.7 pmol/L. |
pmc-6029167-1 | A 58-year-old man was referred for ophthalmologic evaluation by the rheumatology department with the diagnosis of IgG4-RD after submandibular gland biopsy showing increased IgG4+ cells (> 200 cells/HPF). Serum IgG4 level was elevated to 1295.0 mg/dL (normal range, 6.1~ 121.4) at the time of diagnosis.
On examination, his uncorrected visual acuities were 20/20 OU. He had orthotropia at distance and at near in the primary position with the alternate prism and cover test (Fig. ). Ductions and versions were full without limitation (Fig. ). Exophthalmometry showed 14.5 mm OU. He remained orthotropic until the last follow-up examination one year later.
Orbit CT images showed enlargement of lymph nodes in both peribronchial areas and right level I/III, right superior rectus, right medial rectus, left lateral rectus, and left inferior rectus muscles (Figs. ), and infiltrative lesions in both lungs and perirenal space. |
pmc-6029167-2 | A 62-year-old woman presented with left upper eyelid swelling which developed 1 year ago. She also had experienced recurrent conjunctival injection for 3 years.
On examination, her uncorrected visual acuities were 20/20 OU. She had orthotropia at distance and at near in the primary position with the alternate prism and cover test (Fig. ). Ductions and versions were full. Marginal reflex distances (MRD) were + 3 OD and + 2 OS. Exophthalmometry showed 16.5 mm OD and 18 mm OS.
Orbit CT showed a 2.5 cm sized enhancing mass in the left lacrimal gland and enlargement of the left lateral rectus muscle belly like a spindle shaped mass (Figs. ). Anterior orbitotomy and lacrimal gland biopsy showed increased positive IgG4 cells (> 30–50 cells/HPF) and positive CD3, CD20 and Ki-67. Serum IgG4 level was 74.0 mg/dL (normal range, 6.1~ 121.4) and IgG2 level was 770.0 mg/dL (165–545). He was diagnosed with IgG4-ROD and treated with oral steroids. |
pmc-6029167-3 | A 66-year-old man was referred from the outside hospital for further evaluation of enlarged extraocular muscles which were incidentally found on CT during evaluation of sinusitis.
On examination, his corrected visual acuities were 20/30 OU. Automatic refraction showed + 0.00 Dsph − 0.25 Dcyl x 110A OD and + 0.25 Dsph − 1.00 Dcyl x 75A OS. He showed 4 Δ of exotropia (XT) and 3 Δ of right hypertropia (RHT) in the primary position, XT 4 Δ and RHT 3 Δ in right gaze, XT 2 Δ and RHT 3 Δ in left gaze, XT 2Δ and RHT 4 Δ in upgaze, and RHT 1 Δ in downgaze. With either right or left head tilt, he showed XT 2 Δ and RHT 3 Δ. Ductions and versions were full (Fig. ). He had intermittent diplopia. MRD were + 2 mm OU. Exophthalmometry showed 18 mm OD and 16.5 mm OS.
Orbit MR imaging showed enlargement of the left lacrimal gland, right medial rectus, right inferior rectus, right lateral rectus, and right inferior oblique with nodular components (Figs. ). Serum IgG4 level was elevated to 429.0 mg/dL (normal range, 6.1~ 121.4). Anterior orbitotomy and lacrimal gland biopsy showed increased positive IgG4 cells (> 50–70 cells/HPF), and focally positive CD3, CD20 and Ki-67 (6%). He was diagnosed with IgG4-ROD and treated with oral steroids. |