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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 30.0-999.0, Cervical Spondylotic Myelopathy Age 30 years and older 2. Diagnosis of CSM with correlative imaging studies (MRI or CT-myelogram) 3. Able to ambulate without assistance and stand without assistance with participant eyes open for a minimum of 10 seconds 4. Able and willing to attend and perform the activities described in the informed consent within the boundaries of the timelines set forth for pre-, and post-operative follow-up History of prior attempt at fusion (successful or not) at the indicated levels, (history of one level fusion is not an exclusion) 2. Major lower extremity surgery or previous injury that may affect gait (a successful total joint replacement is not an exclusion) 3. BMI higher than 35 4. Neurological disorder (beside cervical spondylotic myelopathy), diabetic neuropathy or other disease that impairs the patient's ability to ambulate or stand without assistance 5. Usage of blood thinners 6. Pregnant or wishing to become pregnant during the study

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioma Glioblastoma Arm 1 Patients must have unmethylated MGMT supratentorial high-grade glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed astro oligodendroglioma or glioblastoma). Arm 2 Patients must have supratentorial methylated MGMT high-grade glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed astro oligodendroglioma or glioblastoma). Both Patients must have MRI or CT with contrast within 28 days prior to starting treatment Patients must have a Karnofsky performance status ≥ 70% (i.e. the patient must be able to care for himself/herself with occasional help from others) Patients must have adequate blood, kidney and liver function Patients must be able to provide written informed consent Patients and their sexual partners must agree to avoid conception while on the study due to possible risks from experimental drugs. Women will need a negative pregnancy test to be on the study Patients may not have any other cancers except skin cancer and localized bladder, prostate, cervical, or breast cancer which were cured more than 3 years ago Patients with other serious diseases Pregnant women Patients getting other cancer treatments Patients with other cancers except for localized skin cancer and localized bladder, prostate, cervical, or breast cancer which were cured more than 3 years ago Patients who have had repeat craniotomy for tumor therapy after receiving radiation therapy and temozolomide treatment Patients who have previously received other treatments for their cancers Patient has previously taken ruxolitinib or is allergic to components of the study drug Use of blood thinners Human immunodeficiency virus (HIV) infection Active hepatitis B or C infection

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 16.0-999.0, Anaplastic Astrocytoma, IDH-Mutant Diffuse Astrocytoma, IDH-Mutant Patients must have histopathologic or molecular confirmation of either IDH-mutant DA or IDH-mutant AA. Acceptable IDH mutations for study any IDH1 mutation at codon 132 or any IDH2 mutation at codon 172 Age >= 16 years. The intended neurocognitive tests have not been validated in children below the age of 16 Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) Hemoglobin > 9.0 g/dL Leukocytes >= 3.0 x 10^9/L Absolute neutrophil count >= 1.5 x 10^9/L Platelets >= 100 x 10^9/L International normalized ratio (INR) =< 1.5 x upper limit of normal (ULN) Partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) =< 1.5 x ULN Patients on a stable dose of anti-coagulation therapy will be allowed to participate if they have no signs of bleeding or clotting and the INR/PT and PTT/aPTT results are compatible with an acceptable risk-benefit ratio as per the investigator's discretion Patients must not have received prior chemotherapy to treat the glioma Patients who are receiving any other investigational agents History of allergic reactions attributed to compounds of similar chemical or biologic composition to CB-839 HCl (telaglenastat) or TMZ Patient must not have received prior radiation therapy to the brain. Prior radiation therapy to the head and neck is also excluded if radiation fields overlap No prior use of Gliadel wafers Patient must have no evidence of either infratentorial or spinal involvement with tumor Patients who are unable to swallow tablets Patients who are at risk for impaired absorption of oral medication including, but not limited to, refractory vomiting, gastric resection/bypass, and duodenal/jejunal resection Patients with uncontrolled intercurrent illness Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for more than 3 years

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Spinal Cord Compression Cauda Equina Syndrome Stereotactic Body Radiotherapy Diagnosis of metastatic malignancy (radiologic or pathologic) 2. Evidence of disease in vertebral body with epidural component such that Bilsky radiologic score is 1c-2 on MRI (abuts spinal cord without cord compression (1c), or spinal cord compression but with visible CSF (2) 3. Motor function (MF) of 3 or greater Surgical candidate 2. Instability of vertebral bodies with or without bony retropulsion requiring surgical intervention or hardware placement 3. Previous radiotherapy course to same region of spine with overlapping fields (prior to phase I course) at discretion of treating radiation oncologist 4. No CT or MRI within previous 3 months 5. Life expectancy estimated <3 months 6. Performance status KPS<40 7. On active chemotherapy or targeted therapy or immunotherapy (must be stopped for at least one week prior to and following) 8. Pregnant or lactating 9. Contraindications to radiotherapy (eg. active autoimmune disease requiring medication) 10. Inability to lie flat comfortably for at least 20 minutes 11. Age < 18

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-80.0, Rectal Cancer pathologically confirmed diagnosis of rectal adenocarcinoma located within 15cm from the anal verge; 2. pelvic radiation with a total dose ≥60Gy for the treatment of rectal cancer; 3. refused surgery as the initial treatment; 4. a complete set of clinical information and follow-up data patients with terminal cancer who received palliative treatment; 2. patients received any treatment before admission to Sun Yat-sen University Cancer Center; 3. patients with second primary cancer

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Ascites, Malignant Patient 1. Male or female adult patients 2. Have ascites due to cancer undergoing treatment at Gloucestershire Hospitals NHS Foundation Trust 3. Planned to have an ascitic tap within a week 4. Thought to have an estimated prognosis of 12 weeks or more 5. Willing and able to provide signed written informed consent Patient Patients who, in the opinion of the clinical team, would be too distressed by the idea of participation. 2. Patients who might not adequately understand verbal explanations or written information given in English. Relative 1. Adult supporting patient participant in Rocket Project 1 2. Happy to support patient with completion of patient diaries Relative Relatives who, in the opinion of the clinical team, would be too distressed by the idea of participation. 2. Relatives who might not adequately understand verbal explanations or written information given in English

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Advanced Cancer Ovarian Cancer Glioblastoma Multiforme Anaplastic Astrocytoma Age 18 years and older Diagnosis of or suspected diagnosis of EOC, HGG, high-grade RT Individual must undergo elective surgery or biopsy to remove tumor tissue Consideration as a candidate for systemic therapy with cytotoxic chemotherapy, targeted small molecule inhibitors or immunotherapy Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 3 Written informed consent in accordance with institutional standards must be obtained from the patient or legal guardian Inability or refusal of the patient or legal guardian to sign a written informed consent Failure to have surgery or a biopsy as part of routine clinical practice Refusal to have the Assay performed on their tissue Known active cancer metastatic to the brain except for patients with brain metastases that have been treated and are considered stable Inability or unwillingness to receive chemotherapy treatment beyond surgery Any coincidental medical condition that, in the Investigator's opinion, would preclude participation in the study or compromise the patient's ability to give informed consent

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 3.0-25.0, Anaplastic Astrocytoma Glioblastoma Malignant Glioma Stratum 1 (IDH wild-type): Patients must be >= 3 years of age and =< 21 years of age at the time of enrollment Stratum 2 (IDH mutant): Patients must be >= 3 years of age and =< 25 years of age at the time of enrollment Patients must have confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1 Newly-diagnosed high-grade glioma such as anaplastic astrocytoma or glioblastoma Negative results for H3 K27M by immunohistochemistry (IHC) Negative results for BRAFV600 mutation by next-generation sequencing (NGS) Patients must have histological verification of diagnosis. Patients with M+ disease (defined as evidence of neuraxis dissemination) are not eligible. Cerebrospinal fluid (CSF) cytology is not required but may be obtained if clinically indicated prior to study enrollment. If cytology is positive, the patient would be considered to have metastatic disease and would, therefore, be ineligible Pre-operative and post-operative brain magnetic resonance imaging (MRI) with and without contrast must be obtained. The requirement for a post-operative MRI is waived for patients who undergo biopsy only. A spine MRI is not required, but may be obtained if clinically indicated. If the spine MRI is positive, the patient would be considered to have M+ disease (defined as neuraxis dissemination) and would be ineligible Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age Peripheral absolute neutrophil count (ANC) >= 1,000/uL (within 7 days prior to enrollment) Patients with the following histologies Diffuse astrocytoma (grade 2) Oligodendrogliomas (any grade) Pleomorphic xanthoastrocytoma (PXA, any grade) Patients with primary tumor location of brainstem or spinal cord Patients with M+ disease (defined as neuraxis dissemination either by imaging or by cytology) Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS) or with features suggestive of AML/MDS Prior allogenic bone marrow transplant or double umbilical cord blood transplantation Patients must not have received any prior tumor-directed therapy including radiation therapy, chemotherapy (tumor-directed therapy), molecularly targeted agents, or immunotherapy for the treatment of HGG other than surgical intervention and/or corticosteroids Lumbar CSF cytology is not required, but may be performed if clinically indicated prior to study enrollment. If lumbar CSF cytology is positive, the patient is considered to have M+ disease and is ineligible

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-60.0, Myelopathy Virtual Reality Patients with myelopathy with neurological level of injury below C4. 2. Both traumatic and non-traumatic myelopathy. 3. Duration of illness less than 6 months Severe orthopedic or medical impairment that interfered with sitting. 2. Upper limb muscle power <3/5. 3. Cognitive or visual impairment

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Lower Extremity Amputation Patients >18 years of age diagnosed with peripheral vascular disease and/or diabetes mellitus Patients undergoing trans-tibial or trans-femoral amputations Patients undergoing amputation for trauma, malignancy, or necrotizing fasciitis with no dysvascular diagnosis Patients who have previously undergone an amputation Patients who were unable to function independently prior to admission Patients admitted to the ICU prior to surgery Attending surgeon does not approve of the patient being enrolled Prisoners Pregnant women

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.115-999.0, Glioma BRAF V600E Pleomorphic Xantho-Astrocytoma Glioblastoma Subjects must have a history of primary brain tumor (including but not limited to glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic ganglioglioma (AG), and anaplastic pleomorphic xanthoastrocytoma (PXA)) Subjects must have a BRAF-V600 mutation identified in previous tissue analysis (may be IHC or PCR based). Allowable mutations V600E, V600K, V600R, and V600D Subjects must be taking dabrafenib at a dose of at least 50mg twice daily (adults only) and / or trametinib at a dose of at least 1mg daily (adults only) for at least 7 days prior to surgery as prescribed by their treating physician. Note: Pediatric patients may be taking any dose of dabrafenib and / or trametinib as prescribed by their treating physician for at least 7 days prior to surgery Subjects must be undergoing surgery for clinical purposes Written informed consent a signed informed consent and/or assent (as age appropriate) for study participation will be obtained according to institutional guidelines Subjects who are receiving any other investigational agents or chemotherapeutic agents Subjects for whom collection of blood, spinal fluid, or tissue samples is unsafe or clinically inadvisable

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-65.0, Multiple Sclerosis Participants who 18-65 years of age MS patients who are ambulatory (Expanded Disability Status Scale score ≤ 5,5 ) in a stable phase of the disease, without relapses in the last 3 month Participants who have orthopedic, vision, hearing, or perception problems

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Metastatic Lung Non-Small Cell Carcinoma Recurrent Lung Non-Small Cell Carcinoma Refractory Lung Non-Small Cell Carcinoma Stage IV Lung Non-Small Cell Cancer AJCC v7 Patients must have histologically or cytologically confirmed metastatic or recurrent non-small cell lung cancer; presence of a mutation in KRAS as detected by a Clinical Laboratory Improvement Act (CLIA)-approved assay is required for patients enrolled in cohort 1; central validation is not required for enrollment If, and only if, cohort 1 is positive (at least 1 out of up to 24 patients experience a confirmed durable response, lasting at least 6 months), then cohort 2 will open; this can occur prior to full enrollment to 24 patients; absence of a mutation in KRAS (KRAS wild type) is required for patients enrolled in cohort 2; central validation is not required for enrollment Patients must have primary resistance to anti-PD-1 or anti-PD-L1 therapy, given as monotherapy or in combination with other agents; patients must experienced progressive disease within 6 months (180 days) of initiating treatment with a PD-1/PD-L1 inhibitor Patients with a sensitizing alteration in EGFR, ALK or ROS1 are eligible provided they have experienced disease progression or intolerance to treatment with an approved EGFR, ALK or ROS1 inhibitor, respectively; patients who have received investigational inhibitors may be eligible following discussion with the study principal investigator (PI) Patients must have disease amenable to core biopsy and be willing to undergo the required research biopsies Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) Leukocytes >= 2,500/mcL Absolute neutrophil count >= 1,000/mcL Platelets >= 100,000/mcL Patients who have not recovered from clinically significant adverse events (other than alopecia) due to prior anti-cancer therapy Treatment with any investigational agent within 4 weeks prior to cycle 1, day 1 Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to cycle 1, day 1 Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed Patients with symptomatic central nervous system (CNS) metastases are excluded Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following are met Evaluable or measurable disease outside the CNS No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm) No history of intracranial hemorrhage or spinal cord hemorrhage

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Anaplastic Astrocytoma All patients must have frozen section biopsy proven anaplastic astrocytoma or glioblastoma multiforme without evidence of multifocal tumor or leptomeningeal metastatic disease or brainstem involvement as well as radiographic evidence consistent with these diagnoses Life expectancy ≥ 12 weeks Patient can receive second treatment of HSV-tk after 6 months Patients should have the following characteristics: newly diagnosed anaplastic astrocytoma or glioblastoma demonstrated by frozen section biopsy, ECOG performance status of 0-1. No evidence of other active malignancy (except squamous or basal cell skin cancers) Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks of the study by the investigator (or his/her designee) with the aid of written information Willing to provide biopsies as required by the study WOCBP must have a negative serum pregnancy test within 7 days prior to the administration of the first study treatment. Women must not be lactating WOCBP and men must practice an effective method of birth control Patients must have adequate baseline organ function as assessed by the following laboratory values before initiating the protocol serum creatinine < 1.5 mg/dL Prior treatment with immunomodulatory therapy, immunotherapy, and/or gene vector therapy in the past 3 months Any cytotoxic chemotherapy, RT, or immunotherapy or any investigational drug within 3 weeks of study treatment start Evidence of multifocal disease, brainstem involvement, or leptomeningeal metastasis, Discrete areas of contrast enhancement connected by abnormal T2 FLAIR signal on MRI scan are not considered multifocal disease, as this represents a single tumor Patients on immunosuppressive drugs (other than steroids for brain edema) Liver disease, such as cirrhosis or active/chronic hepatitis B or C History of or current alcohol misuse/abuse within the past 12 months Known or suspected allergy or hypersensitivity to any component of the proposed regimen (gene vector/Valacyclovir) Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications (Valacyclovir) No active malignancy except for non-melanoma skin cancer or in situ cervical cancer or treated cancer from which the patient has been continuously disease free for more than 3 years The presence of active CNS toxoplasmosis infection or Progressive Multifocal Leukoencephalopathy demonstrated on CT or MRI imaging

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Coronary Stenosis Acute Coronary Syndrome Acute Myocardial Infarction Atheromatous Plaques Atheroscleroses, Coronary Non-ST Elevation Myocardial Infarction (nSTEMI) Patients aged over 18 years old that have signed the written informed consent Patients with ST and non-ST segment elevation myocardial infarction (as stated in the Third Universal Definition of Myocardial Infarction) at 30 days prior to randomization unwillingness or incapacity to provide informed consent (and if consent of legal guardian or family is not available) acute myocardial infarction at the moment of randomization (as these patients are referred to the hospital for emergency invasive coronary angiography and revascularization) conditions that present an estimated life expectancy of under 5 years acute renal failure or terminal stage chronic kidney disease pregnancy or lactation and women of reproductive age who are not using any contraceptive method allergy and history of allergic reactions to iodine contrast media active malignancy or malignancy within the last 1 year prior to enrollment patients who, in the opinion of the investigators are not compliant and will not present for study visits

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 50.0-999.0, Accidental Falls adults aged 50 years or over Community-dweller independent to be standing and walking, with or without walking aids interest to participate in the study severe sensorial impairments (deafness or blindness) cognitive impairments which precludes the ability to comprehend the questionnaires and functional tests included in the screening protocol

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Urinary Retention Neurogenic Bladder Males age ≥ 18 with clinical diagnosis of neurogenic lower urinary tract dysfunction (NLUTD) 2. Must be clinically suitable and capable of safely managing bladder using an intermittent voiding or indwelling strategy Must have stable urinary management history: no significant changes in bladder management regimen within past 12 months OR Must have urodynamic profile suitable for C2P, as assessed via urodynamics study within past 12 months (including bladder capacity > 200mL without uninhibited bladder contractions) 3. Subject's lower urinary tract anatomy must fall within the ranges serviceable by the C2P device, as specified in the investigational device instructions for use (IFU) Active symptomatic urinary tract infection, as defined in this protocol (subjects may receive the device after Urinary Tract Infection (UTI) has been treated) 2. Significant risk profile or recent history of urethral stricture (e.g. stricture within past 90 days) 3. Significant risk profile or recent history of clinically significant autonomic dysreflexia (AD) (e.g. History of hospitalization due to AD within past 12 months) 4. Significant intermittent urinary incontinence (between catheterizations) 5. Uninhibited bladder contractions and/or vesico-ureteral reflux that is not reliably controlled with medication or alternate therapy (e.g. Botox injections) 6. Pre-existing urinary pathologies and/or morphological abnormalities of the lower urinary tract or bladder (assessed during in-depth medical screening, including cystoscopy and urine analysis) 7. Urinary tract inflammation or neoplasm 8. Urinary fistula 9. Bladder diverticulum (outpouching) > 5cm in size 10. Chronic pyelonephritis (secondary to upper urinary tract infection(s) within past 6 months) 11. Impaired kidney function or renal failure 12. Active gross hematuria 13. Active urethritis 14. Bladder stones 15. Dependence on an electro-magnetic medical implant (e.g. cardiac pacemaker or implanted drug pump) or external device 16. Any unsuitable comorbidities as determined by the investigator or complications related to use of certain medications 17. Any physical or cognitive impairments that diminish the subject's ability to follow directions or otherwise safely use the C2P System

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-70.0, Glioblastoma Multiforme of Brain Anaplastic Astrocytoma of Brain Newly diagnosed glioblastoma and anaplastic astrocytoma age between 18 and 70 years Karnofsky Performance Scale Index equal or more than 60 percent signed informed consent chronic hepatic renal failure cardiac failure history of hematologic malignancies

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 40.0-70.0, HIV AIDS Aging current cannabis use (within 6 months) based on self-report 2. able to perform study procedures, including ability to ambulate independently 3. adequate hearing and vision 4. for HIV+ women use of stable HAART for at least 6 months pregnancy 2. current illicit drug use other than cannabis 3. request for substance use treatment 4. current parole or probation 5. recent history of significant violent behavior (within 12 months) 6. major current Axis I psychopathology (e.g.,bipolar disorder, suicide risk, schizophrenia) 7. current use of psychiatric medication known to influence cognition 8. significant uncontrolled medical illness (such as uncontrolled diabetes or hypertension, clinically significant laboratory abnormalities, liver function tests (LFTs)>3x upper limit of normal) 9. history of active heart disease within 12 months 10. history of dementia 11. severe hand tremor 12. history of Central Nervous System (CNS) diseases or injury 13. poor English fluency. All participants will be consented and compensated for their effort as approved by the Institutional Review Boards (IRBs) of each participating institution (see human subjects)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-75.0, Chronic Urinary Retention Have chronic urinary retention caused by lower motor neuron damage Age 18 to 75 years Have chronic urinary retention caused by injury of sacral plexus, cauda equina and sacral spinal cord, pelvic floor nerve lesion after pelvic surgery and peripheral neuropathy due to diabetes Have postvoid residual urine volume 300 mL or more and sensation of bladder Bladder contractile index is more than 100 or more Duration of disease is more than 3 months Intermittent clean catheterization or indwelling catheterization Sign informed consent and participate in the study voluntarily Have urinary retention due to bladder outlet obstruction (bladder neck contracture, urethral stricture, prostate cancer, prostatic hyperplasia, etc.) Have urinary system tumors or stones Have detrusor underactivity due to other non-lower motor neurogenic disease Have bowel and urinary disorder due to lesions or injuries of thoracic spinal cord, cervical spinal cord and brain After suprapubic cystostomy Have heart, liver, kidney, mental disorders or coagulation disorders Have been implanted a cardiac pacemaker, sacral nerve stimulation electrode, pudendal nerve stimulation electrode, or bladder stimulation electrode During pregnancy or in lactation

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Spinal Tumor Surgical treatment and pathological confirmation of spinal glioma in our department and is the first case without any treatment before operation The tumor is recurrent or has been treated before operation

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Second Degree Perineal Tear During Delivery - Delivered Episiotomy; Complications Anesthesia, Local Maternal age > 18 years of age Gestational age≥34 weeks of gestation Vaginal delivery Perineal laceration (2PT/Epi) Effective epidural anesthesia No known hypersensitivity to bupivacaine or amino-amide anesthetics Medical history of a chronic pain syndrome Intrapartum morphine use

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Cervical Myelopathy The are a clinical diagnosis of CM including the signs of corticospinal lesions together with the appropriate radiographic findings Patients with acute spinal cord injuries, prior spinal intervention, with shrapnel or other metal or electronic implants in their bodies (such as pacemakers, aneurysm clips, surgical devices, metallic tattoos on the head, etc.), with claustrophobia and pregnant women will be excluded

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Chronic Post-stroke Hemiplegic Patients Stroke patient visited Shinchon Severance Hospital Rehabilitation Department Adults over 19 years Ischemic or hemorrhagic stroke confirmed by brain magnetic resonance imaging or computed tomography Patients who have had a stroke for more than 3 months Those who have hemiplegia after a stroke If the walking pattern is abnormal and the walking speed is less than 0.8m / sec Those who have a score of K-MMSE score of 24 or higher in the Korean version A person who can walk independently with 3 or more points in the Functional Ambulation Category (FAC) classified as 0 ~ 5 according to the degree of need for assistance in walking The patients who understand the research and have voluntary participation Those who have difficulty walking before stroke Modified Ashworth scale of the lower extremity muscle is 3 or more Patients with ataxia Severe lower extremity joints, osteoporosis, and untreated fractures Patients who weigh more than 135kg Damage of the skin in contact with the machine during robot walking Patients who underwent orthopedic or neurosurgical surgery within 6 months of the start of the study uncontrolled hypertension or orthostatic hypotension Patients who are likely to spread pathogenic microorganisms due to contact Not cutting

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-65.0, Patellofemoral Pain Syndrome ASA class I-II Diagnosed with patellofemoral pain syndrome Patients with confirmed radiographic evidence explaining knee pain Legally incompetent or mentally impaired (e.g. minors, Alzheimer's subjects, dementia, etc.) Younger than 18 years of age or older than 65 Any patient considered a vulnerable subject Patients with impaired circulation, peripheral vascular compromise, Previous revascularization of the extremity, or severe hypertension Patients with Sickle cell anemia or venous thromboembolism Patients with Sickle cell anemia or venous thromboembolism Patients with cancer or Lymphectomies Patients with increased intracranial pressure

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Anaplastic Ependymoma Ependymoma Ependymomas Stage 1 (Cohort 1 and 2) Cohort 1 Histologically confirmed by NCI Laboratory of Pathology intra-cranial or spinal RELA- fusion ependymoma of grade I, II or III Has received two or fewer prior chemotherapy regimens Cohort 2 Histologically confirmed by NCI Laboratory of Pathology intra-cranial or spinal RELA-fusion ependymoma of grade I, II or III Has received more than two prior chemotherapy regimens Stage 2 (Cohorts 3 and 4) Cohort 3 Histologically confirmed by NCI Laboratory of Pathology intra-cranial or spinal non RELA-fusion ependymoma of grade I, II or III Has received two or fewer prior chemotherapy regimens Cohort 4 Histologically confirmed by NCI Laboratory of Pathology intra-cranial or spinal non RELA-fusion ependymoma of grade I, II or III Has received more than two prior chemotherapy regimens Anticancer treatment within designated period of time before enrollment including surgery within 14 days needle or core biopsy within 7 days prior cytotoxic therapy within 28 days vincristine within 14 days nitrosoureas within 42 days procarbazine administration within 21 days non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid (radiosensitizer does not count) within 7 days; Avastin within 21 days. Any questions related to the definition of non-cytotoxic agents should be directed to the NCI Principal Investigator Treatment with any investigational agent within 28 days before enrollment History of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless patient is in complete remission and off all therapy for that disease for a minimum of 3 years

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Solid Tumor, Adult Pre-screening registration 1. Signed pre-screening Informed Consent Form 2. Patients with recurrent or metastatic solid tumor (any histology), who progress after at least one standard therapy for advanced disease 3. Patient willingness and acceptance to participate in the immunology research is mandatory 4. At least one lesion accessible to biopsy without putting patient at risk 5. Biopsies obtained previously (within a maximum of 12 weeks before pre-screening visit), outside this protocol, for TIL assessment can be also considered for patient selection. Fresh tumor biopsies for subsequent translational studies will be used as baseline and collected at pre-screening (when biopsy will be performed for TIL status) or at screening (when archival biopsy will be used for TIL status). Biopsy from metastatic lymph nodes is accepted. 6. Eastern Cooperative Oncology Group (ECOG) clinical performance status: 0-1 for all patients, independently of the number of previous lines of therapy. 7. Life expectancy of ≥ 12 weeks 8. Patients with Glycose-6-Phosphate Dehydrogenase (G6PD) deficiency or any other hereditary coagulation disorder are excluded, as well as patients with clinical history of Reye syndrome 9. Adequate serology defined by the following laboratory results obtained during pre-screening period (day-28 to day-14). 1. Seronegative for HIV infection (anti-HIV-1/-2) 2. Seronegative for hepatitis B infection (HBs Ag, total anti-hemoglobin C (HBc), anti-HBs). Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen HBsAg test and a positive anti-HBc antibody test) are eligible, if hepatitis B virus (HBV) DNA test is negative. 3. Seronegative for hepatitis C infection (anti-HCV): if a patient has positive anti-HCV antibody, a negative hepatitis C virus (HCV) RNA need to be obtain to register the patient. Study registration 1. Signed main study Informed Consent Form 2. Absence of tumor-infiltrating intraepithelial Cluster of differentiation-8 positive T cells (CD8+ T cells) by immunohistochemistry (IHC) on baseline biopsy defined as <5 CD8+ cells per high power field of tumor 3. At least one lesion accessible to biopsy without putting patient at risk 4. Number of metastatic lesions viewed on Positron emission tomography-computed tomography (PET/CT) scan: for both Phase Ia and Phase Ib, the patient may have any number of metastatic lesions. A maximum of 10 metastatic lesions visible by PET/CT scan will be irradiated at the investigator's discretion. It is at the discretion of the investigator to a metastatic site from the radiation field that, due to the radiotherapy volume, dose or location too close to a healthy organ, may put the patient at risk of suffering from radiation induced toxicity. If this would be the only metastatic site to be irradiated, the concerned patient will be excluded from the study. 5. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol 6. Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment: 1. Absolute neutrophil count ≥ 1.5 g/L (without granulocyte colony-stimulating factor support within 2 weeks prior registration) 2. White Blood Cell (WBC) counts > 2.5 g/L and < 15 g/L 3. Lymphocyte count ≥ 0.5 g/L 4. Platelet count ≥ 100 g/L (without transfusion within 1 week prior registration) 5. Hemoglobin ≥ 90 g/L (Patients may be transfused to meet this criterion but it should not be done within 1 week prior registration) 6. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase ≤ 2.5 x ULN (with the exception for patients with documented liver metastases: AST, ALT and alkaline phosphatase ≤ 5 x ULN) 7. Serum bilirubin ≤ 1.5 x ULN (with the exception for: patients with known or suspicion of Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled) 8. Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or Partial Thromboplastin Time (PTT) is within therapeutic range of intended use of anticoagulants; Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. 9. Serum albumin > 25 g/L 10. Serum creatinine ≤1.5 x ULN or creatinine clearance ≥ 40 ml/min on the basis of Cockcroft-Gault Formula 7. No prior radiation therapy in areas of desired radiation 8. Patients may have had prior therapy provided a washout period of 4 weeks prior to registration is allowed. Exception: hormone therapy for breast and prostate cancer is allowed to be continued during the study. 9. Recovery from any toxic effects of prior therapy before registration to ≤ Grade 1 per the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE v4.03) except for toxicities described below, as they do not put at risk the patient's condition and do not require systemic immunosuppressive steroids at any dose, including but not limited to: fatigue, alopecia, skin disorders, stable neuropathy, endocrinopathies requiring replacement treament. Note: for other medical conditions, or for any other toxicity with a higher grade but controlled by adequate treatment, prior discussion and agreement with the trial chair is mandatory. Note: Patients may have undergone surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less. 10. For women of childbearing potential (WOCBP: sexually mature women who have not undergone a hysterectomy, have not been naturally post-menopausal for at least 12 consecutive months or have a serum follicle-stimulating hormone (FSH) < 40 Millions International Units (mIU)/ml): 1. Agreement to use 2 acceptable methods of contraception during participation in the trial and for 6 months after last study combined treatment and after 5 months of maintenance treatment 2. Women must have a negative urine pregnancy test within 7 days before registration. A positive urine test must be confirmed by a serum pregnancy test, or menopausal as per National Comprehensive Cancer Network (NCCN) guidelines. 11. For men: agreement to use 2 acceptable methods of effective contraception during participation in the trial and for 7 months after last study treatment (combined or maintenance treatment). Female partners of men who take part in this trial must also use at least one method of effective contraception during the trial and 7 months after last study treatment (combined or maintenance) Patients with soft tissue sarcoma, glioblastoma, or lymphoma are excluded. 2. Pregnant or breast-feeding women. 3. Symptomatic brain or leptomeningeal disease; any brain metastases must be stable for at least 6 months 4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) 5. Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab a) Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. 6. Life expectancy of < 12 weeks 7. Current, recent (within 4 weeks prior to registration), or planned participation in an experimental drug study 8. New York Heart Association Class II or greater congestive heart failure 9. History of myocardial infarction or unstable angina within 6 months prior registration 10. History of stroke or transient ischemic attack within 6 months prior registration 11. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior registration) 12. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) 13. Patients with active peptic or duodenal ulceration (within 4 weeks prior to registration) 14. Current or recent (within 14 days prior registration) treatment use of dipyramidole, ticlopidine, clopidogrel, cilostazol, prasugrel, or ticagrelor 15. Current or recent (within 14 days prior registration) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose 1. Prophylactic anticoagulation for the patency of venous access devices is allowed, provided the activity of the agent results in an International Normalized Ratio (INR) < 1.5 x ULN and aPTT is within normal limits within 2 weeks prior registration. 2. Prophylactic use of low molecular-weight heparin (e.g., enoxaparin) is allowed. 16. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins or allergy to biopharmaceuticals produced in Chinese hamster ovary cells 17. Known hypersensitivity to any component of the Investigational Medicinal Products (IMPs) 18. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. The following exceptions are considered: 1. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study. 2. Patients with controlled Type I diabetes mellitus on a stable insulin regimen are eligible 19. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), druginduced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest Computerized Tomography (CT) scan. Exception: history of radiation pneumonitis in previous radiation field (fibrosis) is permitted provided that this area does not undergo current low dose irradiation as part of this protocol. 20. Severe infections within 4 weeks prior registration including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia 21. Signs or symptoms of infection within 2 weeks prior registration 22. Received therapeutic oral or IV antibiotics within 2 weeks prior registration. Exception: patients receiving routine antibiotic prophylaxis (e.g., to prevent chronic obstructive pulmonary disease exacerbation or for dental extraction) are eligible. 23. Prior allogeneic stem cell or solid organ transplant 24. Administration of a live, attenuated vaccine within 4 weeks before registration. Exception: influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine within 4 weeks prior registration or at any time during the study. 25. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications 26. Patients who have received prior treatment with anti-Programmed Cell Death-1 (PD1), anti-Programmed Cell Death Ligand-1 (PD-L1) or anti-Cytotoxic T-lymphocyte Associated 4 (CTLA-4) may be enrolled, provided at least 5 half-lives (approximately 75 days) have elapsed from the last dose to the registration and there was no history of severe immune-mediated adverse effects from such therapy (NCI CTCAE Grade 3 and 4). 27. Treatment with systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-a), interleukin-2 (IL-2)) for any reason within 6 weeks or five half-lives of the drug, whichever is shorter, prior registration 28. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents) within 2 weeks prior registration 1. Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) or physiologic replacement doses (i.e., prednisone 5-7.5 mg/day) for adrenal insufficiency may be enrolled in the study. 2. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 13.0-999.0, Chronic Exertional Compartment Syndrome Male or female ages 13 and over Patients with any combination of the following symptoms who would otherwise be evaluated for CECS Symptoms of leg pain worsened with activity and relieved by rest Pain that is generalized in the anterior or lateral compartments of lower leg Numbness or tingling in the distribution of the superficial peroneal nerve Sensation of "slap foot" or anterior/lateral compartment weakness Able to exercise for CPT testing: Patients will be asked to go through a standardized warm up on a treadmill with increasing speed and incline settings until symptoms are achieved. They will maintain exercise for a minimum of five minutes or to patient tolerance Known vascular disease Neurogenic or radicular symptoms

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-65.0, Myasthenia Gravis Being diagnosed with MG by a neurologist Aged between18-65 years To be in Stage II or III according to the Clinical Classification of the Medialia Gravis Functional Assessment (MGFA) The Mini Mental Test score should be over 24 in order to be cooperative to the physiotherapist's instructions To volunteer to participate in the study Having a cognitive problem and having a Mini Mental Test score below 24 To have had myasthenic crisis in the last month Modification of medical treatment and dose in the last month Systemic, orthopedic and neurological disease in addition to the disease Participation in physiotherapy program in the last six months

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Common Peroneal Neuropathy Participants were eligible for in the study if they had clinical and motor electrophysiological evidence suggesting common peroneal mononeuropathy at the fibular neck Clinical evidence of common peroneal mononeuropathy at the fibular neck Numbness of the antero lateral aspect of the lower limb from about midway between the knee and the ankle, most of the dorsal aspect of the foot and toes and the web space between the first and second toes Weakness of the leg muscles innervated by the peroneal nerve. The strength of the tibialis anterior (TA), extensor hallucislongus (EHL), and peroneius longus muscles was tested using the Medical Research Council (MRC) rating scale. Electrophysiological Motor localizing evidence of common peroneal mononeuropathy at the fibular neck: Peroneal motor nerve conduction velocity decrement ≥10 m/s across the fibular neck segment; or focal conduction block, defined as compound motor action potential (CMAP) amplitude and area reduction ≥ 50% across the fibular neck segment Participants were excluded if any of the following was detected Historical or clinical signs suggesting coexisting neurological conditions (e.g. polyneuropathy and motor neuropathy) Foot drop with symptoms, signs or radiological findings of L5 radiculopathy in association with CPN Symptoms or signs suggesting systemic clinical illness like diabetes mellitus, renal failure, and hepatic failure Previous surgery for peroneal nerve

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 50.0-80.0, Lumbar Spinal Stenosis Intermittent Claudication Meet the requirements for a clinical diagnosis of DLSS combined with a MRI or computed tomography (CT)-based radiological diagnosis of central sagittal diameter stenosis of the lumbar spinal canal Have neurogenic intermittent claudication (IC) characterized by progressive pain, numbness, weakness, and tingling of the buttocks and/or legs when standing or walking or with extension of the back, which are relieved upon sitting, lying down, or bending forward [22]; they must always walk in flexion or hunchback posture Have pain of an intensity ≥4 in the buttocks and/or legs when walking, standing, or extending the back, as measured using the Numerical Rating Scale (NRS) Have pain in the buttock and/or leg that is more severe than their pain in the lower back Have a Roland-Morris score of at least 7 Have received a MRI or CT scan within 1 year that showed the anterior posterior diameter of the canal was ≤12 mm Are aged 50-80 years Have provided signed consent and exhibit willingness to participate in the trial Congenital stenosis of the vertebral canal, indications of surgery for DLSS (e.g., segmental muscular atrophy, bowel and bladder disturbances), spinal instability requiring surgery, lumbar tuberculosis, lumbar metastatic carcinoma, or vertebral body/vertebral stenosis segment compression fracture Severe vascular, pulmonary, or coronary artery disease with limited lower extremities motility Clinical comorbidities that could interfere with the collection of data related to pain and walking function such as fibromyalgia, chronic widespread pain, amputation, stroke, Parkinson's disease, spinal cord injury, and dementia Cognitive impairment, such that they are unable to understand the content of the assessment scales or provide accurate data A history of lumbar surgery Plans to become pregnant within 12 months or are already pregnant Received acupuncture treatments for DLSS within the previous 30 days Neurogenic IC mainly manifesting as numbness, weakness, or paraesthesia of the lower extremities instead of pain

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 40.0-80.0, Carpal Tunnel Syndrome Male or female patients, above 40 years of age Able to understand and sign informed consent Pain associated with mild to moderate carpal tunnel syndrome in a single wrist Numbness and tingling in the median nerve distribution Nocturnal Numbness Weakness and/or atrophy of the thenar musculature Demonstrate positive Phalen's Test of the affected extremity Demonstrate positive Tinel's Test of the affected extremity Sensory impairment defined as a loss of 2-point discrimination Have recent (within 3 months) electro-diagnostic evidence of Carpal Tunnel Syndrome • Currently receiving treatment for carpal tunnel syndrome History of surgical carpal tunnel release Pregnancy Diabetes not controlled by medication Radiculopathy i.e., cervical radiculopathy, diabetic radiculopathy Thoracic outlet syndrome Compromised skin integrity Past history of traumatic event, surgery, or congenital impairment of the forearm, wrist, or hand

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Urinary Retention Neurogenic Bladder Urologic Diseases Males age ≥ 18 with clinical diagnosis of significant urinary retention 2. Must be clinically suitable and capable of safely managing bladder using an intermittent voiding or indwelling strategy Must have stable urinary management history as determined by the Investigator OR: Must have urodynamic profile suitable for the Gen 2 Connected Catheter (including bladder capacity > 200mL without uninhibited bladder contractions) 3. Subject's lower urinary tract anatomy must fall within the ranges serviceable by the Gen 2 Connected Catheter device, as specified in the Investigational Device Instructions for use (IFU) Active symptomatic urinary tract infection (UTI), as defined in this protocol (subjects may receive the device after UTI has been treated) 2. Significant risk profile or recent history of urethral stricture (e.g. stricture within past 90 days) 3. Significant risk profile or recent history of clinically significant (uncontrolled) autonomic dysreflexia (AD) 4. Significant intermittent urinary incontinence (between catheterizations) 5. Uninhibited bladder contractions and/or Vesicoureteral reflux that is not reliably controlled with medication or alternate therapy (e.g. Botox injections) 6. Pre-existing urinary pathologies and/or morphological abnormalities of the lower urinary tract or bladder (assessed during in-depth medical screening, including cystoscopy and urine analysis) 1. Urinary tract inflammation or neoplasm 2. Urinary fistula 3. Bladder diverticulum (outpouching) > 5cm in size 4. Chronic pyelonephritis (secondary to upper urinary tract infection(s) within past 6 months) 5. Impaired kidney function or renal failure 6. Active gross hematuria 7. Active urethritis 8. Bladder stones 7. Dependence on an electro-magnetic medical implant (e.g. cardiac pacemaker or implanted drug pump) or external device 8. Any unsuitable comorbidities as determined by the investigator or complications related to use of certain medications 9. Any physical or cognitive impairments that diminish the subject's ability to follow directions or otherwise safely use the Connected Catheter System 10. Catheter Assessment Tool screening yields unacceptable results

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-100.0, Gliosarcoma Glioma Pathologically Confirmed Glioma after completion of planned biopsy or resection. High grade glioma histologies Glioblastoma High Grade or Malignant Glioma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Gliosarcoma Mixture of any of the above histologies Low Grade Histologies Astrocytoma Grade II or low grade glioma Oligodendroglioma Patients who cannot undergo MRIs. 2. Patients who are allergic to gadolinium based contrast agent 3. Patients who have cardiac pacemaker or other electronic or metal implant 4. Patients who have chronic kidney disease judged sufficient to them from the clinically indicated contrast enhanced MRI. 5. Female patients who is pregnant

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Arthroplasty, Replacement, Hip Arthroplasty, Replacement, Knee Urinary Retention ASA grade I III BMI under 36 kg/m^2 Scheduled surgery for primary total hip or knee replacement Age 18+ years Contraindications or failure of neuraxial anesthesia Patients must not be outpatient total hip or knee procedure Known intercurrent UTI, incontinence, or urinary retention not addressed by pre-operative urologic consultation and correction Pregnancy Current nicotine, alcohol or drug abusers Pre-operative narcotic use (any narcotic consumption within 3 days prior to surgery) Post operative parenteral narcotic administration Allergy or intolerance to liposomal bupivacaine, bupivacaine, celecoxib, dexamethasone and/or pregabalin

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-55.0, Chronic Musculoskeletal Pain Tennis Elbow Musculoskeletal Pain Lateral Epicondylitis Patients suffering from chronic pain due to tennis elbow for at least 3 months A clinical diagnosis of chronic lateral epicondylalgia Pain associated with functional activities such as gripping and pain with resisted contraction of the wrist extensors or extensor carpi radialis brevis, or with passive stretching of the wrist extensors Clinical diagnosis of chronic lateral epicondylalgia on both sides, cervicothoracic spinal pathology, other upper limb musculoskeletal disorders or neurological disorders Pregnancy Drug addiction defined as the use of cannabis, opioids or other drugs Previous or current neurologic, musculoskeletal or mental illnesses defined as an on-going systemic condition Lack of ability to cooperate Current use of medications that may affect the trial e.g. analgesics, anti- inflammatory drugs Consumption of alcohol, caffeine, nicotine or painkillers throughout the study period Past history of chronic pain, neurological or psychiatric conditions Participation in other pain trials throughout the study period and one month prior to participation Participation in more than two sessions of muscle training exercises per week involving the upper limb and/or lower back

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Hypertension At least one visit to SCF providers or Community Health Aides within the previous year 2. Alaska Native or American Indian 3. At least 18 years old 4. Hypertension diagnosis based on International Classification of Disease (ICD) version 9 and/or ICD version10 codes 5. Systolic BP ≥ 130 mmHg recorded at 1 or more clinic visits in the past 18 months, OR systolic BP ≥ 130 mmHg at the study screening visit 6. Ability to provide informed consent 7. Willingness and ability to use a HBPM 8. Willingness to complete the necessary data collection procedures, including transmission of BP measurements and permission for study staff to access EHR and/or PHR data Currently pregnant

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Complex Regional Pain Syndromes Fibromyalgia Stroke Traumatic Brain Injury Osteoarthritis Back Pain Sciatica Patients with a diagnosis of stroke (of any cause), traumatic brain injury or chronic pain condition of more than 3 months duration (e.g. back and referred leg pain; complex regional pain syndrome; fibromyalgia) who are undergoing an inpatient or out-patient rehabilitation programme Motor neglect as assessed by standard clinical examination by a physiotherapist trained to detect such motor neglect (EV). This is defined as weakness and functional impairment without a loss of strength, reflexes or sensation Patients with active serious medical problems that might affect their ability to participate in the exercise protocol (e.g. ongoing sepsis; recent myocardial infarction) Patients who are unable to use treadmill safely as judged by the screening physiotherapist (EV) Patients who are unable to give informed consent, either through issues relating to competency or to language Patients with significant previous experience of virtual reality rehabilitation

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Angiospastic; Disorder Interventional revascularization of a coronary lesion Member or beneficiary of a social security system Informed of the study Language barrier Minor Pregnant woman Person under guardianship Person deprived of his/her liberty Refusal to participate

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, IDH1 wt Allele Recurrent Anaplastic Astrocytoma Recurrent Glioblastoma Recurrent Gliosarcoma Recurrent Malignant Glioma Subjects must be willing and able to provide informed consent, undergo and comply with all study assessments and adhere to the protocol schedule Patients with recurrent malignant GBM or gliosarcoma will be eligible. Patients with recurrent anaplastic astrocytoma with wild-type IDH-1 gene will also be eligible if there is a significant enhancing mass on magnetic resonance imaging (MRI) because their prognosis/behavior is similar to GBM. A pathology report constitutes adequate documentation of histology for study inclusion. Subjects with an initial diagnosis of a lower grade glioma are eligible if a subsequent biopsy is determined to be GBM and there is a significant enhancing mass on MRI Patients must show unequivocal evidence for tumor recurrence or progression by MRI scan after failing prior surgical resection, biopsy, chemotherapy or radiation. A baseline MRI must be performed within 24 days prior to registration. Biopsy is encouraged at the time of recurrence if it is unclear that there is recurrent tumor. However, biopsy is not required if the practicing physician thinks that there is adequate radiographic and clinical evidence for recurrence Patients must be able to undergo endovascular treatment based on Doppler studies showing internal carotid artery (ICA) that is less than 50% occluded For patients undergoing resection for biological endpoints, tumors must be surgically resectable at the time of baseline evaluation and craniotomy for tumor resection would be part of their standard medical care Tumors must be > 1.0 cm in diameter with upper limit of 5 cm maximal diameter Patients must have a Karnofsky performance score >= 70 Patients must have a life expectancy of at least 16 weeks Absolute granulocyte count >= 1,500 prior to starting therapy Platelet count of >= 75,000 prior to starting therapy Histology other than astrocytoma grade IV (GBM or gliosarcoma), although astrocytoma grade III that is IDH-1 wild-type will be included Tumor foci detected below the tentorium or beyond the cranial vault Tumor within the posterior fossa Tumor with leptomeningeal spread Difficulty in obtaining vascular access for percutaneous procedure Ipsilateral carotid stenosis (> 50%, by Doppler studies) Thrombophilias or primary hematological diseases Transfusions or medications (G-CSF) to treat pancytopenia or other hematological conditions < 28 days prior to baseline/day 0/hMSC-DNX2401 administration Biologic/immunotherapy within 2 weeks of baseline Clinical or laboratory evidence of inflammatory and/or autoimmune disorders

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-99.0, Astrocytoma, Grade II Astrocytoma, Grade III Willing and able to provide written informed consent Stated willingness to comply with all study procedures and availability for the duration of the study Life expectancy of at least 3 months Histologic confirmation of WHO Grade II or III astrocytoma---mixed oligoastrocytomas are permitted /19q intact per FISH and/or ATRX mutation(s) per immunohistochemistry or next-generation sequencing (e.g. Foundation Medicine, Caris, or similar CLIA-certified sequencing service) Mutational identity determined by CLIA-certified sequencing including: 1. IDH1/2 wildtype (i.e. lack of detectable mutations on the sequencing report) and 2. TERT promoter mutation Karnofsky performance status ≥70% Maximal safe resection---biopsy alone is allowed Completed standard chemoradiation with total RT dose of at least 40 Gy and concurrent temozolomide (75mg/m2 daily dose with 80% prescribed dose completed) Patients with a tumor that was biopsied or resected in the past followed by observation only without definitive chemoradiation and/or chemotherapy given will be eligible, as long as: repeat maximal surgical resection (biopsy only allowed) has been performed, definitive temozolomide/RT treatment meets the above, and adjuvant temozolomide treatment is planned Prior treatment with anti-angiogenic agents including bevacizumab Prior treatment with TTFields Progressive disease (according to RANO criteria) after temozolomide/RT Actively participating in another clinical treatment trial intended to treat the underlying astrocytoma Females who are pregnant or breastfeeding Significant co-morbidities at baseline (within 2 weeks prior to adjuvant temozolomide start) which would prevent adjuvant temozolomide treatment: 1. Thrombocytopenia (platelet count < 100 x 103/μL) 2. Neutropenia (absolute neutrophil count < 1.5 x 103/μL) 3. CTC grade 4 non-hematological toxicity (except for alopecia, nausea, vomiting) 4. Significant liver function impairment AST or ALT > 5 times the upper limit of normal 5. Total bilirubin > 2 times upper limit of normal 6. Significant renal impairment (GFR ≤ 30 ml/min) Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias A skull defect such as missing bone with no replacement Bullet fragments embedded the skull

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 35.0-65.0, Hypertension Office blood pressure between 130-179 and 80-110 mmHg for systolic and diastolic blood pressure, respectively Non-engaged in structured exercise programs in the last 3 months before the beginning of this study Able to perform the proposed exercises Underlying cardiovascular disease in the last 24 months such as acute myocardial infarction, angina, stroke or heart failure Diseases that reduce life expectancy Smokers BMI >39.9 kg/m² Diabetic proliferative retinopathy

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 1.0-31.0, B Acute Lymphoblastic Leukemia B Lymphoblastic Lymphoma Down Syndrome All B-ALL patients must be enrolled on APEC14B1 and consented to Screening (Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement for B-LLy patients. B-LLy patients may directly enroll on AALL1731 Age at diagnosis Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS) Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS) Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or without DS) B-ALL patients without DS must have an initial white blood cell count < 50,000/uL (performed within 7 days prior to enrollment) B-ALL patients with DS are eligible regardless of the presenting white blood cell count (WBC) (performed within 7 days prior to enrollment) Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on a bone marrow (BM) aspirate OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis can be established by a pathologic diagnosis of B-ALL on a BM biopsy OR a complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells Patient must not have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior history of transient myeloproliferative disease (TMD) are not considered to have had a prior malignancy. They would therefore be eligible whether or not the TMD was treated with cytarabine With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1731 For patients receiving steroid pretreatment, the following additional apply Non-DS B-ALL patients must not have received steroids for more than 24 hours in the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to initiation of the steroids DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV steroids within 4 weeks of diagnosis Patients who have received > 72 hours of hydroxyurea B-ALL patients who do not have sufficient diagnostic bone marrow submitted for APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells Patient must not have acute undifferentiated leukemia (AUL) Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be known prior to enrollment) Note: DS patients with CNS3 disease are eligible but will be assigned to the DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-65.0, Lipedema Subject diagnosed with lipedema according to the of revised Wold Subject did not participate in any exercise program within the last three months No pregnancy / breastfeeding History of acute infection, cancer, inflammatory rheumatic / connective tissue diseases History of cardiovascular or musculoskeletal problems that may prevent them from participating in the exercise program

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Hodgkin Disease Lymphoma, Large-cell, Anaplastic Male and female participants 18 years or older by the time of enrollment. 2. Histologically confirmed diagnosis of cHL or sALCL. 3. Newly diagnosed participants, or participants with RR cHL or RR sALCL at the time of enrollment, or participants with RR cHL or RR sALCL within 3 years prior to in the Study Unconfirmed diagnosis of cHL or sALCL. 2. Current, previous (within the last 3 years) or planned (for the next 2 years) participation in interventional clinical trials. 3. Participation in the non-interventional study CHL-5001 "An international, multi-centre, non-interventional retrospective study to describe treatment pathways, outcomes, and resource use in participants with classical Hodgkin lymphoma (B-HOLISTIC)" (Sponsor is Takeda Pharmaceuticals International AG). 4. Participants for whom the minimum study dataset was not available from their hospital medical records

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-84.0, Osteoarthritis, Hip undergoing elective primary hip replacement surgery American Society of Anesthesiologists physical status 1-3 hip fracture contraindication to spinal anesthesia (refusal, coagulopathy or recent use of anticoagulant medication that prevents spinal anesthesia, local or systemic infection) any other reason deemed significant by attending anesthesiologist any patient requiring a wheelchair for ambulation or who cannot walk 25 feet with or without an assist device at time of surgery presence of neuropathy in posterior thighs or buttocks use of greater than the equivalent of morphine 25 mg IV (oxycodone 30 mg PO) daily any patient deemed a poor candidate for spinal anesthesia as determined by the attending anesthesiologist

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 40.0-70.0, Prostatic Hyperplasia Male patients presenting with lower urinary tract symptoms to urology outpatient clinic 2. According to the European Association of Urology Guidelines: 1. International prostate symptom score> 8 2. Prostate volume> 40 ml 3. Q max <15 ml /sn 3. Patients who did not receive any treatment for lower urinary tract symptoms and applied for the first time 4. Patients who have not undergone lower urinary tract surgery Patients who had undergone medical and surgical treatment for lower urinary tract symptoms 2. Patients with accompanying urethral stricture 3. Patients with neurological diseases (Parkinson's, Multiple Sclerosis etc ...) 4. Patients with spinal cord trauma 5. Patients with indication for surgical treatment at the time of initial admission (Macroscopic hematuria, bladder stone, urinary retention, upper urinary tract dilatation)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 1.0-24.0, B Acute Lymphoblastic Leukemia B Lymphoblastic Lymphoma Central Nervous System Leukemia Mixed Phenotype Acute Leukemia Testicular Leukemia B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to studies (Part A) prior to treatment and enrollment on AALL1732. Note that central confirmation of MPAL diagnosis must occur within 7 business days after enrollment for MPAL patients. If not performed within this time frame, patients will be taken off protocol APEC14B1 is not a requirement for B-LLy patients but for institutional compliance every patient should be offered participation in APEC14B1. B-LLy patients may directly enroll on AALL1732 White blood cell count (WBC) for patients with B-ALL (within 7 days prior to the start of protocol-directed systemic therapy) Age 1-9.99 years: WBC >= 50,000/uL Age 10-24.99 years: Any WBC Age 1-9.99 years: WBC < 50,000/uL with Testicular leukemia CNS leukemia (CNS3) Steroid pretreatment White blood cell count (WBC) for patients with MPAL (within 7 days prior to the start of protocol-directed systemic therapy) Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL are eligible for AALL1731, regardless of NCI risk group) With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1732 Patients who have received > 72 hours of hydroxyurea within one week prior to start of systemic protocol therapy Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells Patients with acute undifferentiated leukemia (AUL) are not eligible For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid pretreatment, the following additional apply T-lymphoblastic lymphoma Morphologically unclassifiable lymphoma Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.25-999.0, Chronic Thromboembolic Pulmonary Hypertension Pulmonary Arterial Hypertension Patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension diagnosed after 1st March 2018 (incident cases) who are aged > 3 months at the time of enrollment fulfill the following hemodinamic mean pulmonary arterial pressure (mPAP) of 25 mm Hg or more, mean pulmonary arterial wedge pressure (PAWP) or left ventricular end-diastolic pressure (PVEDP) of 15 mm Hg or less, pulmonary vascular resistance (PVR) of 3 Woods. Patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension diagnosed before 1st March 2018 (prevalent cases) who are aged > 3 months at the time of enrollment fulfill the following hemodinamic mean pulmonary arterial pressure (mPAP) of 25 mm Hg or more, mean pulmonary arterial wedge pressure (PAWP) or left ventricular end-diastolic pressure (PVEDP) of 15 mm Hg or less, pulmonary vascular resistance (PVR) of 3 Woods

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, High Grade Glioma BRAF V600E BRAF V600K Anaplastic Astrocytoma Anaplastic Pleomorphic Xanthoastrocytoma Gliosarcoma Glioblastoma Patients receiving any other standard or investigational agents are ineligible. 2. Patients with history or current evidence of the following conditions are excluded: neuromuscular disorder with associated elevated CK (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy), pancreatitis, retinal vein occlusion, uncontrolled HIV, or Hepatitis B/C. An exception will be made for (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months and for subjects with cleared HBV and HCV infections, who may enroll in the study. 3. Patients must have measurable (defined by at least 1 cm x 1 cm) contrast-enhancing disease by MRI imaging within 30 days of starting treatment. 4. The following intervals from previous treatments are required to be eligible weeks from the completion of radiation weeks from an anti-VEGF therapy weeks from a nitrosourea chemotherapy weeks from a non-nitrosourea chemotherapy weeks or 5 half-lives from any investigational (not FDA-approved) agents weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.) 5. Patients must be 18 years of age or older. 6. Patients must have a Karnofsky Performance (KPS) Status ≥ 60% 7. Patients must have adequate organ and marrow function within 30 days of starting treatment. 8. Patients must be able to provide written informed consent. 9. Women of childbearing potential must have a negative serum pregnancy test prior to study start. Women of childbearing potential must agree to use adequate contraception (intrauterine device, barrier, or other non-hormonal method of birth control; or abstinence) and not to donate ova from screening through 30 days after the last dose of study drug. Male participants must also agree to use adequate contraception and not to donate sperm from screening until 90 days after the last dose of study drug. 10. Patients must be maintained on a stable or decreasing dose of systemic corticosteroid regimen (no increase for 5 days) prior to baseline MRI. Topical and inhaled steroid treatment is allowed. 11. Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder. Patients with other malignancies must be disease-free for ≥ 2 years. 12. Patients must be able to swallow tablets and capsules. 13. Patients must have a tumor tissue form completed and signed by a pathologist (see Section 9.6.4). The tumor tissue form must indicate availability of archived tissue. The archived tissue should be from the most recent tumor resection, demonstrating active tumor when sufficient tissue is available. If sufficient tissue is not available from the most recent surgery, then tissue from an earlier surgery is acceptable, if available, including from the initial resection at diagnosis Patients receiving any other standard or investigational agents are ineligible. 2. Patients with history or current evidence of the following conditions are excluded: neuromuscular disorder with associated elevated CK (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy), pancreatitis, retinal vein occlusion, uncontrolled HIV, or Hepatitis B/C. An exception will be made for (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months and for subjects with cleared HBV and HCV infections, who may enroll in the study. 3. Known hypersensitivity or contraindication to any component of binimetinib or encorafenib or their excipients 4. Current use of a prohibited medication (including herbal medications, supplements, or foods), or use of a prohibited medication ≤ 7 days prior to the start of study treatment. 5. Patient has not recovered to ≤ Grade 1 non-hematologic toxic effects of prior therapy before starting study treatment. Note: Stable chronic conditions (≤ Grade 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies) are exceptions and may enroll. 6. Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, any of the following History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) ≤ 180 days prior to start date Congestive heart failure requiring treatment (New York Heart Association Grade ≥ 2) Left ventricular ejection fraction (LVEF) < 50% as determined by MUGA or ECHO Uncontrolled hypertension defined as persistent systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite current therapy History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia) Triplicate average baseline QTc interval ≥ 480 ms. 7. Impairment of gastrointestinal function or disease which may significantly alter the absorption of study drug (e.g., active ulcerative disease, uncontrolled vomiting or diarrhea, malabsorption syndrome, small bowel resection with decreased intestinal absorption), or recent (≤ 90 days) history of a partial or complete bowel obstruction, or other conditions that will interfere significantly with the absorption of oral drugs. 8. History of recent (≤ 90 days) thromboembolic or cerebrovascular event such as transient ischemic attack, cerebrovascular accident, or hemodynamically significant (massive or sub-massive) deep vein thrombosis or pulmonary emboli (DVT/PE). Note: Patients with DVT/PE that does not result in hemodynamic instability may enroll as long as they are anticoagulated for at least 4 weeks. Note: Patients with DVT/PE related to indwelling catheters or other procedures may enroll. 9. Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible. 10. Pregnant women are excluded from this study because the effects of encorafenib and/or binimetinib on a fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with encorafenib or binimetinib, breastfeeding should be discontinued if the mother is treated with encorafenib and/or binimetinib. 11. Patients who previously received BRAF or MEK inhibitors are excluded (including but not limited to dabrafenib, vemurafenib, encorafenib, sorafenib, trametinib, binimetinib, cobimetinib, or selumetinib). 12. Patients will be excluded if their tumor harbors a known RAS activating mutation. This does not need to be specifically tested for eligibility. 3.4 Additional for Surgical Arm Patients must meet the above / for consideration with one exception. Patients with a BRAF-V600 E or K mutated low-grade glioma for whom there is a strong clinical suspicion of progression to high-grade would also be eligible for this arm. Additionally: 1. Patients must have a clinical indication for a tumor surgery. 2. No a priori contraindication to biospecimen collection (blood, tumor, CSF)

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-90.0, Stroke Weakness of Extremities as Sequela of Stroke All patients with acute hemorrhagic or ischemic stroke documented clinically and by neuroimaging. 2. Medically stable from a cardio-respiratory stand point so that they can participate in daily therapies. 3. Depressed patients will be included in the study 4. Patients able to stand alone 5. Patients able to provide a written informed consent, from cognitively intact patients (admission Mini Mental Scale Examination [MMSE] greater than or equal to 21) Aphasic patients unable to communicate 2. Confused patients 3. Patients medically unstable 4. Patients unable to stand alone 5. Refusal to provide written informed consent

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 20.0-60.0, Chronic Low-back Pain Adults (both male and female) with non-specific low back pain for more than three months Age range: between 20 and 60 years Willingness of the patient to participate in the study, and written informed consent signed and personally dated by the patient Chronic non-specific low back pain clinically diagnosed as repeated lumbar sourness and swelling pain or a chronic progressive process, accompanied by (i) X-ray examination to lumbar vertebrate fractures, spondylolysis, spondylolisthesis and severe osteoporosis, and/or (ii) MRI with normal signal or low nucleus pulposus signal Age less than 20 or greater than 60 years Specific causes of back pain (e.g., cancer, fractures, spinal stenosis, infections) Complicated back problems (e.g., prior back surgery, medico-legal issues) Possible contraindications for acupuncture (e.g., coagulation disorders, cardiac pacemakers, pregnancy, seizure disorder), and conditions that might confound treatment effects or interpretation of results (e.g., severe fibromyalgia, rheumatoid arthritis) Conditions making treatment difficult (e.g., paralysis, psychoses, or other severe psychiatric problems based on the judgment of a physician investigator and/or a T score >60 on the psychological assessments performed during Session 1) Prior acupuncture treatment for back pain; 1 year minimum for any other condition The intent to undergo surgery during the time of involvement in the study History of cardiac, respiratory, or nervous system disease that, in the judgment of a physician investigator, precludes participation in the study because of a heightened potential for adverse outcome (e.g., asthma, claustrophobia) Presence of any contraindications to MRI scanning (e.g., cardiac pacemaker, metal implants, fear of closed spaces, pregnancy) Active substance abuse disorders within the last 24 months, based on subject self-report

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Adults Living in Long Term Care Scott fall risk of 2-17 (this is the current range used by the Glebe Centre, there have been 0 falls during transportation to the equipment and during each session of the BikeAround system) Sufficient visual abilities to observe images on the domed screen Able to comprehend and communicate in English Adequate attentional capacity to remain focused on the pedalling task Minimum height requirement of 5'2" or 157cm in order to successfully fit the BikeAround system's stationary bike Physical limitations (as determined by the Glebe Centre healthcare/physiotherapy team) that prevent use of the jDome bike Cognitive impairment (as determined by the Glebe Centre healthcare/physiotherapy team) Inability to sustain attention Inability to follow one-step commands Known behavioural abnormalities (e.g. overly aggressive behavior) that in the opinion of the clinical care team might impede any meaningful participation in the project Those who are in the opinion of attending physician or clinical team too unwell to participate in the project Fully unable to complete outcome measures indicated (Section 7, Outcomes)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 35.0-85.0, Osteoarthritis, Knee Knee Pain Chronic Key Male or female 35 to 85 years of age (inclusive) Diagnosis of moderate to severe pain in the index knee due to OA Pain in the non-index knee is less than pain in the index knee Body mass index ≤40 kg/m² Experienced treatment failure with at least 2 prior categories of therapies Able to understand and complete study-related forms and communicate with the Investigator and/or site staff. Key Evidence or history of a serious coagulopathy or hemostasis problem, such as inherited bleeding disorders or thrombocytopenia History of or current condition of poorly controlled hypertension, QTc prolongation, history of risk factors for Torsades de Pointes, or family history of long QT syndrome; or is using concomitant medications that prolong the QT interval Received index knee injections with corticosteroids within 30 days, or hyaluronic acid within 3 months, or platelet-rich plasma within 6 months prior to the injection day Pre-existing osteonecrosis, subchondral insufficiency fracture, severe bone on bone OA, or knee pain attributable to disease other than OA Instability or misalignment in the index knee Concurrent use of opioids or indications other than knee pain History within the past 2 years of substance abuse, including alcohol Allergy or hypersensitivity to chili peppers, capsaicin, resiniferatoxin, acetaminophen, tramadol, or radiographic contrast agents Female participants who are pregnant, planning on becoming pregnant, or currently breastfeeding Any medical condition or comorbidities that, in the Investigator's opinion, could adversely impact study participation or safety, conduct of the study, or interfere with pain assessments

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Astrocytoma Glioblastoma Subjects must satisfy the following to be enrolled in the study: 1. Men and women ≥ 18 years of age,) with recurrent or progressive WHO Grade II Diffuse Astrocytoma, Grade III Anaplastic Astrocytoma or recurrent WHO Grade IV Glioblastoma . 2. Subjects must have previously completed standard or a hypofractionated course of radiation therapy and have been exposed to procarbazine, lomustine and vincristine (for Grade II Astrocytoma), including those who have progressed on (or not been able to tolerate due to medical comorbidities or unacceptable toxicity) standard anticancer therapy, with radiation completed > 12 weeks prior to the first CC-90010 dose (Day 1). 3. Subject must be in first or second recurrence. 4. Subject must have archival tumor tissue suitable for genetic testing and must give permission to access and test the tissue. 5. Subject is considered an appropriate candidate for surgical resection of the recurrent tumor tissue (salvage resection). 6. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1. 7. Subject must meet laboratory values at screening Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L without growth factor support for 7 days (14 days if subject received pegfilgrastim) Hemoglobin (Hgb) ≥10 g/dL Platelet count (plt) ≥100 x 10^9/L Serum potassium concentration within normal range, or correctable with supplements Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x Upper Limit of Normal (ULN) Serum total bilirubin ≤ 1.5 x ULN Serum creatinine ≤ 1.5 x ULN or measured glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m2 using an exogenous filtration marker such as iohexol, inulin, 51Cr EDTA or 1 iothalamate, or creatinine clearance of ≥ 50 mL/min using Cockroft-Gault equation Serum albumin > 3.5 g/dL PT (or INR) and APTT ≤ normal range 8. Females and males must agree to contraceptive methods and avoid conceiving throughout study and up to 46 days (females) and 106 days (males) following last dose of CC-90010 The presence of any of the following will a subject from enrollment: 1. Subject has received anti-cancer therapy (either approved or investigational) within ≤ 4 weeks (6 weeks for nitrosoureas) or 5 half-lives, whichever is shorter, prior to starting CC-90010. If subject received prior immunotherapy (immune checkpoint inhibitor, vaccine, etc.), a 2 week wash-out is required. For a subject treated with the Optune-TTF device, a 2 day period without use is required. 2. Toxicities resulting from prior chemotherapy, surgery, or radiotherapy must have resolved to ≤ NCI CTCAE (version 5.0) Grade 1 prior to starting CC-90010 treatment (with the exception of Grade 3 alopecia). 3. Subject has undergone major surgery ≤ 4 weeks or minor surgery ≤ 2 weeks prior to starting CC-90010 or subject who has not recovered from surgery. 4. Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) ≥ NCI CTCAE Grade 2, despite medical management, or any other significant GI disorder that could affect the absorption of CC-90010. 5. Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages. 6. Evidence of CNS hemorrhage on baseline MRI or CT scan (except for post-surgical, asymptomatic Grade 1 hemorrhage that has been stable for at least 4 weeks). 7. Subject who requires increasing doses of corticosteroids to treat symptomatic cerebral edema within 7 days of study therapy. 8. Known symptomatic acute or chronic pancreatitis. 9. Impaired cardiac function or clinically significant cardiac diseases, including any of the following LVEF < 45% as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO) Complete left bundle branch or bifascicular block Congenital long QT syndrome Persistent or clinically meaningful ventricular arrhythmias or atrial fibrillation QTcF ≥ 480 msec on Screening ECG (mean of triplicate recordings); a marked baseline prolongation of QT/QTc interval, using Fridericia´s QT correction formula History of additional risk factors for Torsade de Pointes (TdP) (e.g. heart failure, hypokalemia, family history of Long QT syndrome Use of concomitant medications that prolong the QT/QTc interval Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting CC-90010 Other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure ≥ 160/95 mm Hg). 10. Pregnant or nursing females. 11. Known HIV infection. 12. Known chronic active hepatitis B or C virus (HBV, HCV) infection. 13. Subject with a requirement for ongoing treatment with therapeutic dosing of anticoagulants or for ongoing prophylactic anticoagulation. Low dose low molecular weight heparin for catheter maintenance is allowed. 14. History of concurrent second cancers requiring active, ongoing systemic treatment. 15. Evidence of history of bleeding diathesis. 16. Subject with known prior episodes of non-arteritic anterior ischemic optic neuropathy (NAION) should be excluded from the study. CC-90010 should be used with caution in subjects with retinitis pigmentosa. 17. Subject has any significant medical condition (e.g., active or uncontrolled infection or renal disease), laboratory abnormality, or psychiatric illness that would prevent the subject from participating (or compromise compliance) in the study or would place the subject at unacceptable risk if he/she were to participate in the study. 18. Subject has any condition that confounds the ability to interpret data from the study. 19. Subject with poor bone marrow reserve as assessed by Investigator such as in the following condition: • Requiring regular hematopoietic support (blood or platelet transfusions, erythropoietin, granulocyte colony stimulating factor [GCSF] or other hematopoietic growth factors) 20. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to starting study drug. • Acute symptoms must have resolved and based on investigator assessment in consultation with the medical monitor, there are no sequelae that would place the participant at a higher risk of receiving study treatment. 21. Previous SARS-CoV-2 vaccine within 14 days of starting drug study

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 40.0-999.0, Spinal Stenosis Lumbar Low Back Pain Peripheral Artery Disease Claudication Lumbar spinal stenosis (LSS) group Central stenosis Pain in at least one leg Neurological signs in the lower limbs (numbness or tingling) Weaknesses in the lower limb Pain relieved by sitting or bending the trunk Peripheral artery disease (PAD) group Claudication while walking Ankle-brachial index < 0.9 Pain relieved by rest Low back pain (LBP) Pain radiating in the lower limb Foraminal stenosis Spinal stenosis with predominant back pain Symptomatic disc herniation Previous lumbar surgery Previous vascular surgery Type 1 diabetes Knee or hip osteoarthritis Hip or knee arthroplasty Inability to provide free and informed consent

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Neurogenic Bladder Urinary Retention Urologic Diseases Males age ≥ 18 with clinical diagnosis of significant urinary retention 2. Must be clinically suitable and capable of safely managing bladder using an intermittent voiding or indwelling strategy 1. Must have stable urinary management history as determined by the investigator OR: 2. Must have urodynamic profile suitable for Gen 2 Connected Catheter (including bladder capacity > 200mL without uninhibited bladder contractions) 3. Subject's lower urinary tract anatomy must fall within the ranges serviceable by the Gen 2 Connected Catheter device, as specified in the Investigational Device Instructions for Use (IFU) Active symptomatic urinary tract infection, as defined in this clinical investigation protocol (subjects may receive the device after UTI has been treated) 2. Significant risk profile or recent history of urethral stricture (e.g. stricture within past 90 days) 3. Significant risk profile or recent history of clinically significant (uncontrolled) autonomic dysreflexia 4. Significant intermittent urinary incontinence (between catheterizations) 5. Uninhibited bladder contractions and/or Vesicoureteral reflux that is not reliably controlled with medication or alternate therapy (e.g. Botox injection) 6. Pre-existing urinary pathologies and/or morphological abnormalities of the lower urinary tract or bladder (assessed during in-depth medical screening, including cystoscopy and urine analysis) 1. Urinary tract inflammation or neoplasm 2. Urinary fistula 3. Bladder diverticulum (outpouching) > 5cm in size 4. Chronic pyelonephritis (secondary to upper urinary tract infection(s) within past 6 months) 5. Impaired kidney function or renal failure 6. Active gross hematuria 7. Active urethritis

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Spinal Cord Injuries Adult individual 18 yr. of age or older. 2. Cognitively intact and capable of giving informed consent. 3. Clinical diagnosis of a non-penetrating traumatic SCI to the cervical spine 4. Patient and Caregiver agree to use Care Connect app or web version of VirTrial platform for virtual visits Prior history of: 1. Recent or ongoing infection, 2. Clinically significant cardiovascular, lung, renal, hepatic, or endocrine disease, 3. Neurodegenerative disorders, 4. Cancer, 5. Immunosuppression as defined by WBC < 3, 000 cells/ml at baseline screening, 6. Chemical or ETOH dependency, 2. Having a contraindication to MRI scans 3. Other acute or chronic medical conditions that, in the opinion of the investigator, may increase the risks associated with study participation or HB-adMSC administration 4. Participation in other interventional research studies. 5. Unwillingness to return for follow-up visits

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 6.0-13.0, Cerebral Palsy, Spastic Ashworth scale score +1-3 age between 6 and 13 years able to accept and follow verbal instructions Gross Motor Function Classification System [GMFCS] levels I-III) unstable seizures, any treatment for spasticity or surgical procedures from 3 months (for botulinum toxin type A injections) Suffering from any other condition that interfered with physical activity

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Anaplastic Astrocytoma Glioblastoma Oligodendroglioma Supratentorial Glioblastoma Presumptive diagnosis of glioblastoma based on magnetic resonance imaging (MRI) imaging within 14 days prior to registration NOTE: Patients who undergo treatment with Toca 511 whose final pathology shows diagnosis other than glioblastoma (e.g. anaplastic astrocytoma or oligodendroglioma or any other histology) will be treated with Toca FC and chemoradiation; however they will not be analyzed in the primary endpoint. The outcomes of these patients will be reported descriptively. Similarly the patients with anaplastic astrocytoma or oligodendroglioma or any other histology treated on the standard-of-care arm will be reported separately and they are allowed to receive the treatment per choice of the treating physician/ investigator (for e.g. radiation therapy [RT] plus temozolomide or RT plus procarbazine-lomustine-vincristine [PCV]) In addition, patients who have undergone biopsy with diagnosis of glioblastoma and who have never received any chemotherapy and/or radiation and are candidates for >= 80% resection of enhancing region are eligible The tumor must be unifocal, confined to the supratentorial compartment and based on the pre-operative evaluation, the patient is a candidate for >= 80% resection of enhancing region Measurable disease preoperatively, defined as at least 1 contrast enhancing lesion, with 2 perpendicular measurements of at least 1 cm, as per Response Assessment in Neuro-Oncology (RANO) The hematoxylin and eosin (H&E) slide and formalin-fixed paraffin-embedded (FFPE) tumor tissue block must be available to be sent for mandatory central pathology review after registration Patients must be able to undergo an evaluation by MRI within 96 hours post surgery to assess extent of resection Karnofsky performance status >= 70 within 14 days prior to registration History/physical examination within 14 days prior to registration Platelet count >= 100,000/mm^3 (within 14 days prior to registration) History of prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years A contrast enhancing brain tumor on MRI that is any of the following Multi focal (defined as 2 separate areas of contrast enhancement measuring at least 10 mm in 2 planes that are not contiguous on either fluid attenuated inversion recovery [FLAIR] or T2 hyperintensity) Associated with either diffuse subependymal or leptomeningeal dissemination; or > 50 mm in any dimension Active infection (excluding skin or toenail infections) requiring systemic antibiotic, antifungal or antiviral therapy within 28 days prior to registration Bleeding diathesis, or must take anticoagulants, or antiplatelet agents, including nonsteroidal anti inflammatory drugs (NSAIDs), at the time of the scheduled resection that cannot be stopped for surgery Known human immunodeficiency virus (HIV) positive status History of allergy or intolerance to flucytosine Swallowing difficulty that would prevent patient from being able to swallow either temozolomide or Toca FC or severe active mal-absorption

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-100.0, Primary Brain Tumor Radiation Toxicity The participant must be 18 years or older and Danish speaking Performance status 0-2 Capable of cooperating on testing Diagnosed with one of the following diagnoses according to WHO 2016 classification 16 and been treated between 2006 and 2016 1. ZM93803 glioma (exclusive glioblastoma) 2. ZM9401/3 anaplastic astrocytoma, IDH mutant 3. ZM9400/3 diffuse astrocytoma, IDH-mutant 4. ZM9411/3 gemistocytisk astrocytoma, IDH mutant 5. ZM9400/3 diffuse astrocytoma, NOS 6. ZM9451/3 anaplastic oligodendroglioma, IDH mutant and 1p/19q-co deleted 7. ZM9450/3 oligodendroglioma, IDH mutant and 1p/19q-co deleted 8. ZM9450/3 oligodendroglioma, NOS 9. ZM9451/3 anaplastic oligodendroglioma, NOS 10. ZM9530/0 meningioma 11. ZM9470/3 medulloblastoma, NOS 12. DD352A pituitary adenoma 13. Other rare brain tumours including skull base sarcomas - Performance status 3-4 Progression after radiation therapy -

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 60.0-999.0, Diabetes Senior Syndrome Frailty Age ≥ 65 years Type 2 diabetes Hispanic ethnicity >3/5 points in the Mini Cog test Score >17 on the Mini Nutritional Assessment Not willing or not able to exercise due to medical issues or physical limitations Malnutrition: Score <17 on the Mini Nutritional Assessment On dialysis Liver disease Cancer HIV/AIDS Other physical/psychological condition preventing participation

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 35.0-85.0, Lower Extremity Arterial Disease (Fontaine Stages IIb-IV) Fontaine stage I-IIa acute limb ischemia age <35 or >85 years fasting < 6 hours time since the last use of tobacco products < 4 hours body mass index ≥ 40 kg/m2 blood pressure ≥ 180/120mmHg unstable angina atrial fibrillation at the time of presentation myocardial infarction, stroke or TIA during the preceding 3 months

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Stroke Movement, Abnormal Postural, Balance 18 years old and over 2. First stroke Recurrent stroke 2. Having other neurological diseases such as brain tumor, Parkinson's Disease 3. Systolic blood pressure greater than 160 mmHg and/or diastolic blood pressure greater than 100 mmHg 4. Having heart failure recorded in patient's file 5. Having joint limitation in functional range 6. Difficulty in communication (i.e. sensory aphasia, severe hearing loss)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-85.0, Intermittent Fasting Obesity, Morbid Comorbidities and Coexisting Conditions Weight Loss Fluid Retention 1. Subjects with complicated obesity grade 2 or higher (Body Mass Index [BMI]>35kg/m2), i.e., obesity associated with renal failure with eGFR<60cc/min or heart failure with preserved ejection fraction (EF) (≥50%) and clinical evidence of fluid retention evidenced by the use of loop diuretic, or the presence of peripheral edema; or treatment in congestive heart failure clinics or history of admission to the hospital for heart failure during the past 3 years; OR • b. Subjects with complicated obesity, grade 2 or higher (BMI>35 kg/m2) [with renal failure as defined above-delete this requirement] and at least one of the following comorbidities: 1) Uncontrolled hypertension despite the use of at least 3 drugs administered at their maximal or close to maximal dose 2) Severe sleep apnea (based on a sleep lab report) 3) Pulmonary hypertension 4) Coronary heart disease 5) Type 2 diabetes mellitus 6) History of stroke (> 3 months prior to the recruitment to the trial) 2) Subjects who failed to lose weight on standard treatment, refuse standard medical treatment or are judged as unable to tolerate/unsuitable to receive standard medical treatment to lower body weight and in whom bariatric surgery is deemed unacceptable due to excessive surgical risk by the referring physician and/ or the PI and / or the patient and fulfill the following 1. Wish to fast 36 hours, twice a week, over three months 2. Committed to attend the clinic at least once a week and perform blood tests every 2-14 days, as detailed in the protocol. 3. Are well trained in-home glucose monitoring and are willing to monitor glucose levels during the fasting days. 4. Are well trained in-home monitoring of blood pressure and are willing to measure blood pressure twice a day during the fasting days. 5. Own and control a dependable means of 24/7 communication device, eg, cell phone, and are committed to avail this route of communication to the study staff Severe renal failure (eGFR<20cc/min) 2. Liver disease other than non-alcoholic fatty liver disease or cardiac cirrhosis or any liver disease with aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase levels>3 times of the upper limit of the normal range, albumin< 3.5 gr% or direct bilirubin>1.2 mg%. 3. Cognitive impairment assessed by a Mini-Mental State Exam (MMSE) score < 24 4. Living in a single household (caretaker is allowed) 5. Age less than 18 or >85 years 6. Pregnancy or intention to conceive or female at the reproductive age not using birth control means. 7. History of documented hypoglycemia during the past year despite attempted adjustment of treatment. 8. Unintended weight loss > 2kg over the past 2 months. 9. The initiation, within the study period of any one of the following medications, including topiramate, lyxumia, byetta, bydureon, belviq, Xenical, victoza, saxenda, trulicity, semaglutide or any other glucagon-like peptide-1 (GLP-1) analog. However, subjects already treated with these agents before the initiation of the trial may be included provided that the medication has been started at least 4 months prior to the beginning of the study and that weight loss during the 2 months preceding the trial did not exceed 2 kgs. 10. A subject who must use drugs whose use is not recommended on an empty stomach and in whom this qualification appears, in the investigator's opinion more critical than the potential chance to lose weight and excrete excess bodily fluids

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Anaplastic Astrocytoma, IDH-Wildtype Glioblastoma, IDH-Wildtype Lung Non-Small Cell Carcinoma Metastatic Malignant Neoplasm in the Central Nervous System Metastatic Malignant Neoplasm in the Leptomeninges Pre-Registration Specific to Dose Escalation Cohort Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) EGFR Status GBM/AA must have EGFR amplification and/or EGFRvIII mutation NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) Pre-Registration Specific to Dose Expansion Cohorts Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) Registration for Dose Escalation and Dose Expansion Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown Pregnant persons Nursing persons Persons of childbearing potential who are unwilling to employ adequate contraception Any of the following prior therapies Any cytotoxic chemotherapy or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen =< 14 days prior to registration In patients with NSCLC, treatment with an EGFR TKI (e.g., erlotinib, gefitinib, afatinib or osimertinib) within 8 days or approximately 5 x half-life, whichever is the longer, prior to registration (if sufficient wash-out time has not occurred due to schedule or PK properties, an alternative appropriate wash-out time based on known duration and time to reversibility of drug related adverse events could be agreed upon by the Investigator and Wayshine) Radiation therapy to the brain =< 12 weeks prior to registration

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Squamous Cell Carcinoma Pilonidal; Cyst, Malignant Surgery Squamous cell carcinoma over pilonidal disease Distant Metastases

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-80.0, Spinal Cord Astrocytoma patients that histologically diagnosed as primary spinal cord astrocytoma patients with spinal cord tumors rather than astrocytoma metastatic astrocytoma tumor sample can not be obtained

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Obturator Jerk in TURBT All patients undergoing TURBT for suspected bladder tumors Consent withdrawal, bladder tumour other than in the lateral wall, unfit for spinal anesthesia and need of general anesthesia or obturator nerve block

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Urinary Retention Underactive Bladder Clinically referred as having bladder problems that have not responded to conservative treatment. Normal clinical care includes referral to implant of Medtronic Interstim neurostimulator at the pudendal nerve. Fully eligible to receive an Interstim implant Adult (18 or older), capable of providing own informed consent and communicating clearly with research team Capable of speaking, reading, and understanding English, as all study questionnaires are standardized assessments only available in English Capable of attending all experimental sessions (Visit 1: pre-stage-1 imaging, Visit 2: stage-1 surgery, Visit 3: CT after stage-2 surgery, Visit 3: cystometrogram test) Implanted materials that prohibit magnetic imaging Any medical problems that prevent an individual from laying flat in an MRI or CT scanner, are are claustrophobic Areflexive or atonic bladder Pregnant or planning to become pregnant. If a woman of child-bearing potential wishes to participate in this study, they will be pre-screened with a test to detect pregnancy Diagnosed neurogenic bladder, pudendal nerve damage, lower motor dysfunction, or other conditions that would affect the neural circuits involved in micturition Unwilling to allow de-identified data to be stored for future use or shared with other researchers

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 3.0-17.0, High Grade Glioma Patients must have a histologically-confirmed recurrent non-metastatic supratentorial WHO Grade III malignant glioma (anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, and anaplastic pleomorphic xanthoastrocytoma) or WHO Grade IV malignant glioma (glioblastoma multiforme, gliosarcoma, malignant glioma NOS) 2. Patients should be candidates for resection/open biopsy of the recurrent tumor and be deemed candidate for placement of an Ommaya reservoir placed intra-cavitary/ intra-tumoral; measurable residual tumor after surgery is not required for study entry 3. Given the lack of a standard of care treatment for children with recurrent grade III/IV gliomas, patients must have completed first-line treatment with 54 Gy of radiation prior to participating in this trial 4. All patients must be ≥ 3 years of age and <18 years of age at the time of study entry into the study 5. Lansky score of 50 or greater if ≤ 16 years of age or a Karnofsky score of 50 or greater if >16 years of age 6. Adequate bone marrow function, without transfusion or growth factors within 21 days of NK cell administration, defined as a white blood cell ≥ 2.5 x 103/microliter, hemoglobin ≥ 9 gm/dL, absolute neutrophil count ≥ 1,000 cells/microliter and platelet count of ≥ 75,000 cells/microliter 7. Patients must be off systemic steroids (except replacement therapy) for at least 3 days prior to NK cell infusion 8. Adequate liver function (ALT, AST and alkaline phosphatase < 2 times ULN, bilirubin < 1.5 times ULN), and adequate renal function (BUN or creatinine < 1.5 times ULN) prior to NK cell 9. Must have recovered from the toxic effects of prior therapy (i.e., NCI-CTCEA version 5 grade 1 or less) 9a. An interval of at least 12 weeks must have elapsed since the completion of initial radiation therapy 9b. At least 6 weeks since the completion of any cytotoxic chemotherapy regimen 9c. For targeted agents only, patient should have recovered from any toxicity of the agent and have a minimum of 2 weeks since the last dose 9d. For patients who have received prior bevacizumab, at least 6 weeks is required before starting study treatment 10. Patients of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation Patients with intra or extra-CNS metastasis 2. Tumor involvement that would require ventricular, brainstem or posterior fossa injection or access through a ventricle or risk of ventricular penetration in order to deliver the NK cells 3. Tumors involving both hemispheres or those involving the subependyma or suspected CSF dissemination 4. Patients undergoing needle biopsies (Open biopsies are the minimum requirement for enrollment) 5. Pregnant or lactating patients 6. Patients on chronic corticosteroid therapy (except for replacement therapy) 7. Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions. All subjects must be afebrile at baseline (i.e., < 38.0 Celsius [C]) 8. Any medical condition that precludes surgery 9. Prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) > 1.5 x ULN 10. Patients with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV), or an auto immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible 11. Evidence of bleeding diathesis or use of anticoagulant medication or any medication which may increase the risk of bleeding. If the medication can be discontinued >1 week prior to NK cell infusion then the subject may be eligible following consultation with the principal investigator (PI) 12. Subjects with significant systemic or major illnesses including but not limited to: congestive heart failure, ischemic heart disease, kidney disease or renal failure, organ transplantation, or significant psychiatric disorder 13. History or current diagnosis of any medical or psychological condition that in the Investigator's opinion, might interfere with the subject's ability to participate or inability to obtain informed consent because of psychiatric or complicating medical problems

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 30.0-65.0, Low Back Pain aged between 30 and 65 y diagnosis of aspecific chronic low back pain minimum of 3 on the NRS score Neuropathic pain or chronic widespread pain Low back spinal surgery in the last three years Low back spinal surgery to osteoporosis and/or traumatic fractures Rheumatic disease Pregnancy or having a baby in the last 12 months Painful disease in evidence through RX, MRI or CT in the last 6 months (listesis, moderate arthrosis, severe, algodystrophy etc.) The subjects have not to be treated with physical or manual therapies or psychotherapy in the last 6 months

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-100.0, Brain Tumor Cognitive Impairment Radiation Toxicity years or older and Danish speaking Performance status WHO 0-2 Capable of cooperating on testing Tumor histology (WHO 2016 classification) of the following types: anaplastic astrocytoma (IDH mutant), diffuse astrocytoma (IDH-mutant), gemistocytic astrocytoma (IDH mutant), diffuse astrocytoma (NOS), oligidendroglioma, meningioma, medulloblastoma (NOS), pituitary adenoma, other brain tumours including skull base sarcomas Glioblastoma Performance status 3-4

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-22.0, Acute Myeloid Leukemia All patients must be enrolled on APEC14B1 and consented to Screening (Part A) prior to enrollment and treatment on AAML1831. Submission of diagnostic specimens must be done according to the Manual of Procedures). Risk stratification will not be possible without the submission of viable samples. Given there are multiple required samples, bone marrow acquisition techniques such as frequent repositioning or performing bilateral bone marrow testing should be considered to avoid insufficient material for required studies. Consider a repeat marrow prior to starting treatment if there is insufficient diagnostic material for the required studies Patients must be less than 22 years of age at the time of study enrollment Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease Patient must have 1 of the following >= 20% bone marrow blasts (obtained within 14 days prior to enrollment) In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy < 20% bone marrow blasts with one or more of the genetic abnormalities (sample obtained within 14 days prior to enrollment) A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell [WBC] count >= 10,000/uL with >= 10% blasts or a WBC count of >= 5,000/uL with >= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (performed within 7 days prior to enrollment) ARM C: Patient must be >= 2 years of age at the time of Late Callback ARM C: Patient must have FLT3/ITD allelic ratio > 0.1 as reported by Molecular Oncology Patients with myeloid neoplasms with germline predisposition are not eligible Fanconi anemia Shwachman Diamond syndrome Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 Any other known bone marrow failure syndrome Any concurrent malignancy Juvenile myelomonocytic leukemia (JMML) Philadelphia chromosome positive AML Mixed phenotype acute leukemia Acute promyelocytic leukemia

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 40.0-80.0, Knee Osteoarthritis Male or female between the age of 40 and 80 with BMI ≤ 40 Monolateral (unless contralateral knee is grade I and asymptomatic) femorotibial knee OA associated or not with femoropatellar knee OA Responding to clinical and radiological of the American College of Rheumatology (ACR) (Appendix 1) Symptomatic for more than 6 months in the most painful knee Radiological Kellgren & Lawrence (K&L) II or III in radiographs from less than 12 months (Appendix 2) Mean knee pain score at rest over the last 24 hours evaluated on VAS (0-100) ≥ 40 (Appendix 3) with a washout period for Paracetamol and oral NSAIDs depending on the half-life of the drug (Appendix 4). The most painful knee is considered Able to follow the instructions of the study Having signed an ICF Related to the OA pathology Bilateral (except asymptomatic and grade I) OA of the knee Radiological K&L grade I or IV (Appendix 2) Chondromatosis or villonodular synovitis of the knee Recent trauma (< 1 month) of the knee responsible of the symptomatic knee Acute inflammatory OA (KOFUS (Knee Osteoarthritis Flare Up Scale) score ≥ 7, Appendix 5) Articular disease resulting from articular dysplasia, aseptic osteonecrosis, acromegaly, Paget's disease, hemophilia, hemochromatosis… Inflammatory disease i.e. rheumatoid arthritis, gout, infectious arthritis, acute calcium pyrophosphate arthritis Pathologies interfering with the evaluation of OA (radiculalgia in the lower limbs, arteritis…..) Presence of another joint (other than the target knee) affected by OA (confirmed in radiographs and symptomatic) Related to treatments

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Spinal Stenosis Intermittent claudication with pain or numbness or weakness of lower limb(s) with or without low back pain An imaging study (MRI or CT) showing single level lumbar spinal stenosis Insufficient conservative treatment (6 weeks) Cauda equina syndrome or progressive neurologic deficit requiring urgent surgical intervention Previous spinal surgery Other comorbid conditions that contraindicating surgery Possible pregnancy that contraindicating radiological examination Age less than 18 years old Combination with 2°spondylolisthesis or segmental instability (slip distance >4mm or angle change >10° in dynamic plain film) Combination with other spinal disorder requiring advanced surgery (such as lumbar stenosis, spondylolisthesis, deformity, fracture, infection, tumor and so on) Equal to or more than two responsible level

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Hamstring Contractures Participants over 18 years of age Athletes from the university teams in the branches of rugby, soccer, basketball or tennis Presence of hamstring shortening in one of the two extremities (positive straight leg elevation test or Straight Leg Raising). It will be considered as a positive test when the participant, in the supine position, shows tension or discomfort in the posterior region of the thigh when passively raising the lower limb for any angle less than 80 ° of hip flexion with extended knee. In the event that the participant presents a bilateral shortening, the limb with the lower elevation will be taken as shortened hamstrings Pain when performing hip or knee movements Musculoskeletal injuries such as fractures, sprains, tears, dislocations, contusions, or joint problems of the lower extremities in the past 3 months Skin disorders such as scars, burns, psoriasis or wounds in the posterior region of the thighs Neurological signs or symptoms such as tingling, loss of sensation in the lower extremities (partial or complete), weakness, changes in color or temperature in the thigh, legs or foot Background or circulatory abnormalities in the lower extremities such as arterial ischemia, venous insufficiency, embolism, post-phlebitic syndrome, lymphedema or deep vein thrombosis Joint hypermobility (positive Beighton hypermobility test) Intake of medications or anti-inflammatory drug treatment at the time of recruitment (includes non-steroidal or steroidal anti-inflammatory drugs) Allergy to metals Apprehension or fear of the application of electric current Belonephobia (extreme and uncontrollable fear of needles and other objects that can cause bloody wounds such as pins, knives, pocket knives, syringes, etc.). Elimination criteria

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Fall Multiple Sclerosis Lower Urinary Tract Symptoms age ≥ 18 years Multiple sclerosis (MS) diagnosis Lower urinary tract symptoms with or without treatment Expanded Disability Status Scale score between 1 and 6.5 relapse of MS in the past month urinary tract infection the day of impossibility to complete the symptoms' questionnaires

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-65.0, Dual Task Amputation Gait Using a transtibial or transfemoral prosthesis for at least 1 year Between the ages of 18-65 To be diagnosed as a neurological, orthopedic, cognitive disorder Having a condition other than amputation that may affect gait Having different permanent disabilities other than amputation Using walking aid

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Weakness of the Lower Limbs For patients Step 1: Patient hospitalized in the Physical Medicine and Rehabilitation department of the Rennes University Hospital following a stay in intensive care or in a Continuing Care Unit, in particular following a COVID-19 infection, and with muscle weakness of the lower limbs with an MRC motor testing on the main muscle segments giving a score less than or equal to 48/60 (diagnostic criterion of ICU Weakness) Steps 2 and 3: Patient hospitalized in one of the ICU of the Rennes University Hospital and presenting post-resuscitation muscle weakness in the lower limbs with MRC motor testing on the main muscle segments giving a score less than or equal to 48/60 (diagnostic criterion of ICU Weakness) Steps 4 and 5: Patient hospitalized in one of the ICU or in the Physical Medicine and Rehabilitation service of the Rennes University Hospital and presenting post-resuscitation muscle weakness in the lower limbs with an MRC motor testing on the main muscle segments giving a score less than or equal to 48/60 (diagnostic criterion of ICU-Weakness) For nursing staff: Step 2: Person with one of the following professions: nursing assistant, nurse, doctor, physiotherapist, and practicing for more than a month in one of the ICU of the Rennes University Hospital . For everyone Person of full age Affiliation to a social security insurance Free, informed and written consent signed For patients History of central neurological event with clinical repercussions Gait disturbances preexisting in ICU hospitalization and limiting the gait perimeter (declaration by the patient) or requiring the use of technical assistance Uncontrolled epilepsy (last crisis occurring less than 6 months old) Persons of full age subject to legal protection (safeguard of justice, curators, guardians), persons deprived of their liberty Pregnant or lactating woman. For caregivers Non-French fluent people Adults over the age of legal protection (safeguard of justice, curators, guardians), persons deprived of their liberty

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 40.0-65.0, Knee Osteoarthritis Knee pain for most days of previous month 2. Age 40 years Knee OA grade 2-3 on kellgren Lawrence grading scale. Unilateral or bilateral (provided that they radiologically have one knee ≤ grade 1 on KL score, and clinically pain ≤2 in VAS. The more severally affected knee will be included in evaluation and treatment) BMI= 25-32 kg/m2 Symptomatic hip OA Hip or pelvis trauma Knee or hip infection Congenital or developmental disorder of lower limbs Intra-articular corticosteroid or hyaluronic acid injection into the knee within the last 3 months. Previous surgery of the affected knee or spine. Significant injury to the knee within the past 6 months. Any disease or medication worsens physical function or hampers with knee evaluation (e.g. rheumatoid arthritis, canal stenosis..)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 20.0-999.0, Healthy Healthy adults (age > 20 years old) Be able to cooperate with the measurements of this study any clinical diagnosis that will influence the measurement, including any history of neuromyopathy angina, acute myocardial infarction in the previous one month pregnancy history of syncope during exercise any musculoskeletal system disorder that unable to perform cardiopulmonary exercise test

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-70.0, Coronavirus Infection Covid19 SARS (Severe Acute Respiratory Syndrome) AKI Subjects over 18 years of age Subjects admitted with a diagnosis of probable SARS-CoV-2 pneumonia Subjects with a diagnosis of SARS-CoV-2 pneumonia confirmed by Real-time quantitative-Polymerase Chain Reaction (qRT-PCR) Subjects with qRT-PCR negative for SARS-CoV-2, but who meet clinical and radiological for COVID-19, and no other causes have been identified Pregnant women Incomplete medical records. Elimination Patients who die within the first 24 hours of entering the institute Patients discharged for any reason not considered death within the first 48 hours, such as voluntary discharge or transfer to other health institutions Patients who during their hospitalization report a positive PCR for other non-respiratory viruses without identifying SARS-CoV-2 Patients who withdraw their consent

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 20.0-999.0, Hemorrhoids Haemorrhoids Piles Hemorrhoidal Disease The age is more than 20 years old, the action is convenient, you can get out of bed and take a bath. 2. Diagnosed as symptomatic grade III or IV hemorrhoid by a surgeon. 3. Accept epidural anesthesia. 4. Perform an open hemorrhoidectomy. 5. After the researcher explains the purpose of the study, the person with a clear consciousness and willing to participate and fill out the study consent form Disease around the anus (fistula, abscess). 2. Urinary tract problems (in the past, there was a hypertrophy of the prostate; the routine urine test for admission had a urinary tract infection, and the bladder volume tester evaluated urinary retention). 3. Take analgesics before surgery

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Central Nervous System Neoplasms Glioblastoma Gliosarcoma, Adult Anaplastic Oligodendroglioma Anaplastic Astrocytoma Pilocytic Astrocytoma Oligodendroglioma Gliomatosis Cerebri Pleomorphic Xanthoastrocytoma Anaplastic Pleomorphic Xanthoastrocytoma Diffuse Midline Glioma, H3 K27M-Mutant Ependymoma Ependymoma, Anaplastic Medulloblastoma Teratoid Rhabdoid Tumor Neuroectodermal Tumors, Primitive Neuroectodermal Tumors Anaplastic Meningioma Atypical Meningioma Choroid Plexus Neoplasms Pineal Tumor Diffuse Astrocytoma Glial Tumor Age ≥ 18 years with a recurrent, primary CNS neoplasm. Primary CNS neoplasms included in this study: glioblastoma and glioblastoma histologic subtypes, gliosarcoma, primary CNS sarcomas, anaplastic glial neoplasms including anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed neuronal-glial tumors, and pilocytic astrocytoma with anaplastic features, diffuse astrocytoma, oligodendroglioma, gliomatosis cerebri, pleomorphic xanthoastrocytoma, anaplastic pleomorphic xanthoastrocytoma, diffuse midline gliomas and histone mutated gliomas, ependymoma, anaplastic ependymoma, and all ependymoma subtypes, medulloblastoma and all medulloblastoma subtypes, ATRT, primary CNS embryonal/primitive neuroectodermal tumors, atypical and anaplastic meningiomas, choroid plexus tumors, and pineal region tumors Advanced disease after having received established standard of care treatment for their disease and have no standard treatment options available Karnofsky Performance Score (KPS) of greater than or equal to 70 Measurable or evaluable disease defined by RANO criteria. The exception will be patients who have had surgery in the past 4 weeks, patients who are post-operative after a maximal resection will be allowed to enroll after 4 weeks from surgical resection Washout for prior investigational or approved cytotoxic chemotherapy is 28 days prior to the first dose of ONC206; 42 days in the case of nitrosoureas; 28 days or 5 half-lives (whichever is less; but not less than 14 days) in case of investigational or approved molecularly targeted agent; 14 days in the case of radiotherapy Patients will be required to enroll on the NCI Neuro-Oncology Branch natural history study (16-C-0151) No major surgery in the prior 4 weeks Patients must have normal organ and marrow function as defined below An available tumor specimen (paraffin-embedded block and/or frozen tissue) from prior resection or biopsy, ≥15 unstained slides for IHC analysis Ability to swallow oral capsules Prior bevacizumab for treatment of high-grade glioma Known HIV-positive test on combination antiretroviral therapy Active cardiac disease Ischemic or hemorrhagic stroke in last 3 months Refractory epilepsy and patients with primary or secondarily generalized seizures in the 28 days before enrollment are excluded. Peri-operative seizures occurring within 7 days of surgery with resolution by day 8 after surgery are allowable. Patients must be on stable doses of one or two seizure medications for 14 days prior to study enrollment Impairment of gastrointestinal (GI) function Concurrent use of warfarin sodium or other Coumadin-derivative anti-coagulants Concurrent use of strong inhibitors or inducers of CYP3A4, 2D6, 1A2, 2C9 and 2C19 are excluded at least 14 days prior to and throughout the study

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 1.0-30.0, Down Syndrome Recurrent B Acute Lymphoblastic Leukemia Patients must be >= 1 and < 31 years at time of enrollment Patients must have first relapse of CD19+ B-ALL (relapse blasts must express CD19) in one of the following categories Isolated bone marrow relapse Isolated central nervous system (CNS) (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse Combined bone marrow with extramedullary relapse in the CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testes Patients with Down syndrome (DS) are eligible in the following categories Isolated bone marrow relapse Combined bone marrow with CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study Patients with B-lymphoblastic lymphoma (B-LLy) Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia Patients with Philadelphia chromosome positive (Ph+) B-ALL Patients with mixed phenotype acute leukemia (MPAL) Patients with known Charcot-Marie-Tooth disease Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype Patients with active, uncontrolled infection defined as Positive bacterial blood culture within 48 hours of study enrollment Receiving IV or PO antibiotics for an infection with continued signs or symptoms. Note: Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline Fever above 38.2 degrees Celsius (C) within 48 hours of study enrollment with clinical signs of infection. Fever without clinical signs of infection that is attributed to tumor burden is allowed as long as blood cultures are negative for > 48 hours

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 25.0-999.0, Hypertension Hypertensive Crisis Hypertensive Emergency Adults who visit the Aga Khan University Hospital Emergency Department with acute severe hypertension able to provide consent to participate Age >25 years of age Meeting the of acute severe hypertension (SBP>180 and DBP>110) Patients not providing consent or are unconscious are excluded from participation

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 35.0-60.0, Coronary Artery Disease Body mass index (BMI) between 20 and 30 kg/m2 Hemodynamic stability with or without use of positive inotropic drugs Absence of arrhythmias and angina Mean blood pressure (MBP) 60 ⩽ MBP ⩽ 100 mmHg Heart rate (HR) 60 ⩽ HR ⩽ 100 bpm without respiratory distress Respiratory rate (RR) ⩽ 20 without signs of infection Previous pulmonary disease and acute lung disease Mechanical ventilation >24 h Left ventricular ejection fraction (LVEF) <35% or >54% Surgical reintervention Intraoperative death or any contraindications for the proposed measurements and/or treatment Contraindications for the 6MWT or any proposed protocol Orthopedic impairments Unstable angina HR >120 bpm at rest, and systolic blood pressure >180 mmHg or diastolic >100 mmHg

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-75.0, Postoperative Pain After a High Tibial Osteotomy adult patients scheduled for a high tibial osteotomy under spinal anesthesia at the Hopital de la Croix Rousse, Hospice Civils de Lyon, France ASA (American Society of Anesthesiology) class between 1 et 3 written informed consent any contraindication for nefopam (known hypersensitivity, past medical history of seizures, urinary retention, benign prostate hyperplasia, angle glaucoma, ischemic cardiomyopathy waiting for revascularization, atrial fibrillation) medical conditions known to influence the pharmacokinetics of nefopam (chronic kidney failure with Glomerular Filtration Rate (GFR) <30mL/min/1,73m2, liver failure, current treatment with rifampicin, carbamazepine, azoles fungicides, macrolides) current treatment with benzodiazepines, anxiolytics, antidepressants, histamine H1 antagonists, neuroleptics, baclofen, thalidomide, barbiturates medical history of gastric or esophageal surgery phenylketonuria pregnancy or breastfeeding past use of oral nefopam

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 45.0-85.0, Patient Satisfaction Bladder Cancer patients with bladder cancer eligible for surgery Patients who refuse to contribute in this study patients who are unfit for surgery patients refusing cystectomy patients with metastatic or inoperable cancer bladder

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Lumbar Spinal Stenosis Low Back Pain Adults aged 18 years or older Previous diagnosis of lumbar spinal stenosis, mild-severe lumbar central canal stenosis identified by MRI or CT scan Symptoms Lower extremity symptoms consistent with neurogenic claudication Pain, weakness &/or numbness triggered by standing or walking, and relieved by sitting Must be able to read English and complete questionnaire Was prescribed Misoprostol specifically for lumbar spinal stenosis Cognitive impairment that renders the patient unable to give informed consent or provide accurate data Clinical co-morbidities that could interfere with the collection of data concerning pain and function Severe vascular, pulmonary, or coronary artery disease that limits ambulation including recent myocardial infarction (within 6 months) Spinal instability requiring surgical fusion Severe osteoporosis as defined by multiple compression fractures or a fracture at the same level as the stenosis Metastatic cancer Excessive alcohol consumption or evidence of non-prescribed or illegal drug use Pregnancy Concordant pain with internal rotation of the hip (or known hip joint pathology) Active local or systemic infection

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-65.0, Low Back Pain Acute Pain patients aged>18 years old initiation of acute low back pain in the 10 days prior to study entry and functionally impairing low back pain, which we defined as a score of > 5 on the Roland-Morris Disability Questionnaire (RMDQ) aged>65 years old history of trauma radicular pain, which we defined as pain radiating below the gluteal folds history of vertebral tumor or metastasis patients who were pregnant or lactating unavailable for follow-up with allergy or contraindication to the investigational medications chronic analgesic use autoimmune diseases or inflammatory rheumatic disorders cardiopulmonary restrictions

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Chronic Pain Have a complex, prolonged axial neck pain or lower back pain Have been followed by a pain management specialist for at least 3 months or have a history of chronic pain for at least 3 months as recorded by physician Be >18 years of age Have a goal and motivation that is adequate in relation to the program offered Be medically prepared Have no major change in interventional treatment or be a surgical candidate Own a smart phone, tablet or computer or have the knowledge to use one Chronic pain requiring imminent surgical intervention Reported severe or acute psychiatric illness, severe anxiety or depression Current history of substance abuse Serious health risks or scheduled major health interventions for other medical reasons Pain related to malignancy Pain duration <3 months Other areas of pain exceeding the amount of back or neck pain Not currently involved in lawsuit or pending litigation

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-80.0, Osteo Arthritis Knee Analgesia Pain, Postoperative Patients scheduled for elective unilateral TKA Planned for regional anesthesia for the procedure Age >=18 Contraindications to regional anesthesia or peripheral nerve blocks Allergy to local anesthetics or any of the study medications Severe hepatic or renal insufficiency Chronic opioid consumption Patient with difficulty comprehending visual analogue scale pain scores Pre-existing lower extremity neurologic abnormalities Patients classified as American Society of Anesthesiologists score 3 or 4 Language/communication barrier

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-70.0, Solid Tumor, Adult Patients with advanced (not radically treatable), recurrent or metastatic solid tumors of any histology with the exception of primary central nervous system tumors, who have received, and then progressed or been intolerant to at least one standard therapy regimen in the advanced or metastatic setting if such a therapy exists, and have been considered for all other potentially efficacious therapies prior to enrollment. If the participant refuses, or is not eligible for these regimens in the opinion of the investigator, the reason must be documented in the medical record. 2. Patients who have previously undergone tumor resection or biopsy and for whom pre-Rapid Expansion Protocol (REP) NeoTIL cultures are ongoing or completed. 3. At least one lesion accessible to biopsy for translational research (TR) at baseline and D30, without putting the patient at unusual risk. 4. Male or female age ≥ 18 to ≤ 70 years at the time of informed consent. Patients aged >70 will be evaluated by the investigator, and decision will be made according to patient's status, upon agreement with the PI. 5. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) of 0 to 2. 6. Life expectancy of greater than 12 weeks. 7. Radiologically measurable disease (as per Response Evaluation in Solid Tumours [RECIST] v1.1). 1. Modified should be used for mesothelioma 2. Prostate Cancer Working Group 3 (PCWG3) should be used for prostate cancer 8. Adequate serology defined by the following laboratory results: 1. Negative test for Human Immunodeficiency Virus (HIV) 2. Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at pre-screening) are not eligible Patients with past/resolved Hepatitis B virus (HBV) infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen (anti-HBc) antibody test) are eligible, if HBV deoxyribonucleic acid (DNA) test is negative HBV DNA must be obtained in patients with positive hepatitis B core antibody prior start of study treatment. 3. Patients with active hepatitis C are not eligible. Patients positive for Hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). 9. Hematology 1. Absolute neutrophil count ≥ 1.0 x 109 cell/L without the support of granulocyte colony stimulating factor (G-CSF). 2. Platelet count ≥ 100 x109 cell/L 3. Hemoglobin ≥ 80 g/L. Subjects may be transfused to reach this cut-off. 10. Coagulation a. International normalization ratio (INR) ≤1.5 times the upper limit of normal (x ULN) unless the subject is receiving anticoagulant. i) Exception: for patients with hepatocellular carcinoma (HCC), the INR may be up to 2.2, as long as the Child-Pugh score is A6 maximum. b. Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless the subject is receiving anticoagulant therapy. 11. Chemistry: 1. Serum alanine transaminase (ALT) / aspartate aminotransferase (AST) ≤ to 3 x ULN i) Exception: ALT/AST considered related to liver metastasis ≤ to 5 x ULN ii) Exception: for patients with HCC serum ALT/AST ≤ to 5 x ULN 2. Total bilirubin ≤1.5 x ULN i) Exception: in patients with Gilbert's syndrome who must have a total bilirubin ≤2.5 x ULN ii) Exception: total bilirubin considered related to liver metastasis ≤3 x ULN iii) Exception: for patients with HCC total bilirubin ≤2.3 x ULN, as long as the Child-Pugh score is A6 maximum 3. Creatinine clearance by Cockcroft-Gault formula ≥ 40 ml/min 12. Adequate cardiovascular function, with documented left ventricular ejection fraction (LVEF) ≥ 45%. This parameter must be documented within 12 weeks before registration 13. Adequate respiratory function with forced expiratory volume in 1 second (FEV1) ≥ 50% predicted, forced vital capacity (FVC) ≥ than 50% predicted and diffusing capacity for carbon monoxide (DLCO) ≥ than 50% predicted corrected. Patients with lung cancer or mesothelioma and values slightly under these limits (but >30% of predicted) can be enrolled after discussion and approval by the PI. These parameters must be documented within 12 weeks before registration 14. At the time the patient receives the NMA chemotherapy regimen (D-7): 1. ≥14 days or 5 half-lives must have elapsed from any chemotherapeutic cytotoxic drug, whichever is shorter. 2. ≥28 days must have elapsed from bevacizumab, aflibercept and other anti-angiogenic antibodies 3. ≥28 days or 5 half-lives (whichever is shorter) must have elapsed from a non-cytotoxic drug including but not limited to trastuzumab, pertuzumab, and other molecular targeted therapy (such as tyrosine kinase inhibitors, etc…) i) Note: In case of probable tumor flare upon stopping of the non-cytotoxic drug, the investigator may decide to shorten this delay, upon agreement of the Principal Investigator (PI), in a case-by-case approach. 4. ≥21 days must have elapsed from the last antibody therapy that could affect an anti-cancer immune response, including but not limited to anti-Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-Programmed cell death protein 1 (PD-1), anti-Programmed death-ligand 1 (PD-L1), anti-Tumor Necrosis Factor Receptor Superfamily, member 4 (OX-40), or anti-Lymphocyte-activation gene 3 (LAG3) antibody therapy or their combination 5. Exceptions: denosumab and biphosphonates are permitted (and will be administered as standard of care [SOC]). 6. Exceptions: androgen-deprivation therapy (ADT) for prostate cancer and hormonal therapy for breast cancer are permitted (and will be administered as SOC). 15. Patients' toxicities from previous therapies must have recovered to at least grade 1 according to National Cancer Institute Common Terminology for Adverse v5.0 (NCI CTCAE v5.0), except for toxicities described below, as long as they do not put at risk the patient's condition and do not require systemic immunosuppressive steroids at immunosuppressive doses, including but not limited to Fatigue Alopecia Skin disorders Stable neuropathy Endocrinopathies requiring replacement treatment Note: For other medical conditions, or for any other toxicity with a higher grade but controlled by adequate treatment, prior discussion and agreement with the PI is mandatory. Note: Patients may have undergone surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less. 16. For women of childbearing potential (WOCBP: sexually mature women who have not undergone a hysterectomy and/or bilateral oophorectomy, have not been naturally post-menopausal for at least 12 consecutive months or have a serum follicle-stimulating hormone (FSH) < 40 milli-International Unit [mIU]/ml): 1. Agreement to follow instructions for method(s) of contraception for the couple, from screening until month 6 post start of NMA chemotherapy of the study. 2. Negative pregnancy test (urine or serum) during screening 17. For men participating in the trial and their female partners: agreement to follow instructions for method(s) of contraception for the couple from screening until month 6 post start of NMA chemotherapy of the study Patients with an active second malignancy, except for 1. non-melanoma skin cancer that has been apparently cured or successfully resected 2. carcinoma in situ as long as they have been adequately treated 3. Any malignancy that can be adequately managed expectantly without compromising prognosis, and after PI agreement. Patients who have a history of malignancy are not considered to have an active malignancy if they have completed therapy since at least 2 years and are considered by their treating investigator to be at ≤ 30% risk for relapse. 2. Patients with symptomatic and/or untreated brain metastases. Patients with definitively-treated brain metastases will be considered for enrollment after agreement with PI, as long as lesions are stable for ≥ 14 days prior to beginning the chemotherapy, there are no new brain lesions, and the patient does not require ongoing corticosteroid treatment. 3. Patients with known peritoneal metastases who have a recent history of intermittent bowel obstruction (even partial), unless such obstruction has been resolved. Agreement with the PI is mandatory. 4. Patients with leptomeningeal carcinomatosis 5. History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any origin) 6. History of recent myocardial infarction or unstable angina, either within six months of enrolment 7. Documented Child-Pugh score of B or C for hepatocellular carcinoma patients with known underlying liver dysfunction 8. Active severe systemic infections within four weeks prior to beginning of NMA chemotherapy. 9. Patient requiring regular systemic immunosuppressive therapy (for example for organ transplantation, chronic rheumatologic disease); all immunosuppressive medications including but not limited to steroids, mycophenolate mofetil, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha (TNF-alpha) agents must have been discontinued within the last two weeks prior to starting NMA chemotherapy. 1. Note: Use of inhaled or topical steroids or corticosteroid use for radiographic procedures is permitted 2. Note: The use of physiologic corticosteroid replacement therapy is permitted. 10. History of severe immediate hypersensitivity reaction to any of the agents used in this study. 11. Women who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant. 12. Subjects for whom there are concerns that they will not reliably comply with the requirements for contraception should not be enrolled into the study. 13. Any serious underlying medical condition that could interfere with study medication and potential adverse events. 14. Any mental or other impairment that may compromise compliance with the requirements of the study. 15. Patient participation in any other study currently receiving treatment. If the patient is in the follow-up period, he/she may be enrolled, as far as the elapsed time since the last previous treatment administration and the preparative regimen (NMA chemotherapy) is respected according to n°14. 16. Participation in a research project using radiation sources exceeding an effective dose of 5 millisievert (mSv) with no direct benefit within the 12 last months

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Transforaminal Lumbar Interbody Fusion Patients undergoing a primary single-level MIS TLIF (Diagnosis: radiculopathy, stenosis, herniated nucleus pulposus, degenerative disc disease, spondylosis, osteophytic complexes, spondylolysis, spondylolisthesis) Patients able to provide informed consent Patients with baseline urinary dysfunction requiring manual bladder emptying via intermittent straight catheterization, suprapubic catheters, or other indwelling catheters. -Allergies or other contraindications to medicines in the post operative urinary retention protocol Lack of consent

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-65.0, Burns Conscious patients Enterally fed >18 years old With inhalation burn In addition to existing burn trauma, those with other trauma (fracture, loss of limb, etc.) Organ dysfunctions or multiple organ failure History of chronic diseases such as diabetes, cholesterol and blood pressure

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-90.0, Hypertension Participants must be age 18 years or older Self-identified as a black or African American male Have uncontrolled hypertension defined as SBP>135 mmHg or DBP>85 mmHg and SBP >130 mmHg or DBP >80 mmHg (in those with diabetes) at the screening Under the age of 18 Does not consent to participate

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 19.0-999.0, Hip Fractures Regional Anesthesia ASA PS 1-4 age: ≥19 baseline pain score (associated with hip fracture): ≥4 patients who do not agree to participate in this study patients with uncontrolled hypertension, hyperthyroidism, severe dementia allergic to ropivacaine contraindicated to spinal anesthesia due to coagulopathy, severe aortic stenosis/mitral stenosis, or active infection on lumbar region patients who are considered ineligible with any other reason by investigators

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-100.0, Covid19 Pain Muscle Atrophy COVID-19 test positive critically ill non-paralized patients in need of mechanical ventilation requiring care in the intensive care unit Subject has a demand-type cardiac pacemaker, implanted defibrillator or other implanted electronic device Active wound infection Below the knee amputations Based on the clinicians decision whether the patient is eligible for the study

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