• Age ≥ 18 years.
• Histological confirmation of esophageal or gastroesophageal junction adenocarcinoma, AJCC 8th ed stage T1-4N0-3M0.
• Candidate for trimodality therapy: neoadjuvant chemotherapy and esophagectomy.
• Surgical consultation to confirm that patient is an appropriate candidate for esophagectomy.
• Medical oncology consultation to confirm that patient is an appropriate candidate for chemotherapy.
• ECOG Performance Status (PS) ≤ 1.
• Negative pregnancy test done ≤ 7 days prior to chemotherapy, for women of childbearing potential only.
• Ability to provide written informed consent and complete questionnaire(s) by themselves or with assistance.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) and provide blood samples for correlative research purposes.

• Clinical or biopsy-proven distant metastatic disease (AJCC 8th ed stage TanyNanyM1).
• Cervical or upper esophageal tumor.
• Prior chemotherapy or radiotherapy for esophageal cancer OR history of radiotherapy to the thorax.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with proper assessment of adverse events.
• Receiving any investigational agent which would be considered as a treatment for the primary neoplasm OR other active malignancy ≤ 1 year prior to registration that is considered by the investigator to interfere with the current treatment or measurement of outcomes.
• Any of the following:
  • Pregnant women;
  • Nursing women;
  • Men or women of childbearing potential who are unwilling to employ adequate contraception.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 11/20/23. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Clinicians:

- All clinicians within identified departments participating are eligible (doctor of medicine [MD]/doctor of osteopathy [DO], fellows/residents, physician assistant [PA]/nurse practitioner [NP]).

Inclusion Criteria
•Patients:

- Adult patients (≥ 18 years of age).

- Appointments at Mayo Clinic in Rochester.

- Non-small cell lung cancer (NSCLC) stage > 1B.

- Eligible by their oncologist for adjuvant treatment.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 11/16/23. Questions regarding updates should be directed to the study team contact.

PRE-REGISTRATION:

• Well- or moderately-differentiated neuroendocrine tumor(s) of bronchial origin (i.e., carcinoid) as assessed by local pathology.
• The pathology report must state ONE of the following:
  • Well- or moderately-differentiated neuroendocrine tumor;
  • Low- or intermediate-grade neuroendocrine tumor.
• Carcinoid tumor (including typical or atypical carcinoid tumors): 
  • Documentation of histology from a primary or metastatic site is allowed.
• Functional (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome) or nonfunctional tumors are allowed.
• Patients with poorly-differentiated or high-grade neuroendocrine carcinoma (i.e., large cell neuroendocrine carcinoma of lung, small cell lung cancer) or mixed tumors (i.e., adenocarcinoid tumor) are not eligible.
• Recurrent or locally-advanced/unresectable or metastatic disease.
• Neuroendocrine tumor of bronchial (i.e., lung) primary site.
• Lesions must have shown radiological evidence of disease progression in the 12 months prior to pre-registration.
• Tumor must have shown somatostatin receptor (SSTR) positivity on 68Ga-DOTATATE PET or other SSTR-PET scan in the 12 months prior to pre-registration; however, documentation of SSTR positivity in the 6 months prior to pre-registration is preferred. SSTR positivity is defined as uptake greater than background liver in all measurable lesions.
• Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 by computer tomography (CT) scan or magnetic imaging (MRI). Any lesions which have undergone percutaneous therapies or radiotherapy should not be considered measurable unless the lesion has clearly progressed since the procedure.
• Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 1 cm with CT or MRI (or ≥ 1.5 cm for lymph nodes). Non-measurable disease includes disease smaller than these dimensions or lesions considered truly non-measurable including: leptomeningeal disease, bone metastases, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung.

REGISTRATION:

• Confirmation of SSTR positivity by Alliance Imaging Core Lab (ICL) at Imaging and Radiation Oncology Core (IROC) Ohio central radiographic review.
• Patients with treatment-naive or previously-treated disease are allowed. Patients with previously-treated disease must have demonstrated radiographic disease progression on the prior therapy.
• No prior treatment with peptide receptor radionuclide therapy (PRRT) (e.g. < lutetium Lu 177 dotatate).
• No prior treatment with mammalian target of rapamycin (mTOR) inhibitors (e.g., deforolimus, everolimus, sirolimus, temsirolimus, etc.).
• Prior treatment with hepatic artery embolization (including bland embolization, chemoembolization, and selective radioembolization) or ablative therapies (i.e., cryoablation, radiofrequency ablation, etc.) is allowed if measurable disease remains outside of the treated area or if there is documented disease progression in a treated site. Prior liver-directed or other ablative treatment must be completed at least 28 days prior to registration.
• Prior treatment with 90-Yttrium radioembolization must be completed at least 6 months prior to registration.
• Radiation therapy (conventional fractionated or stereotactic ablative) to the lung and/or mediastinum must be completed at least 28 days prior to registration.
• Prior treatment with systemic anticancer therapy must be completed at least 28 days prior to registration (except for somatostatin analogs in patients with functional tumors). Continuation of treatment with somatostatin analogs while on protocol therapy is allowed provided that the patient:
  • Has functional tumors (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome);
  • Has been on a stable dose of somatostatin analog therapy for at least three months;
  • Has previously demonstrated radiographic disease progression while on somatostatin analog therapy.
• Patients must have completed any major surgery at least 28 days prior to registration. Complete wound healing from major surgery should occur prior to registration.
• Patients should have improvement of any toxic effects of prior therapy (except alopecia, fatigue, and other non-reversible toxic effects such as neuropathy from cisplatin) to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, grade 1 or less.
• Not pregnant and not nursing, because this study involves:
  • An investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown;
  • An agent that has known genotoxic, mutagenic, and teratogenic effects.
  • Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 14 days prior to registration is required.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Hemoglobin ≥ 8.0 g/dL.
• Platelet count ≥ 75,000/mm^3.
• Absolute neutrophil count (ANC) ≥ 1,500/mm^3.
• Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance ≥ 40 mL/min.
• Calculated by the Cockcroft-Gault equation -ION:
• Total bilirubin ≤ 2.0 x ULN.
• In patients with Gilbert's syndrome, if total bilirubin is > 2.0 x ULN, then direct bilirubin must be =< 2.0 x ULN.
• Albumin ≥ 2.8 g/dL.
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x ULN.
• No known central nervous system metastases unless adequately treated, stable, and off steroid support for at least 14 days prior to registration.
• No other currently active malignancy that requires therapy or is expected to require therapy during the study (excluding non-melanoma skin cancers or in situ carcinomas, such as breast or cervical).
• No uncontrolled diabetes mellitus, defined as fasting glucose > 200 mg/dL, despite optimal medical therapy.
• No known uncontrolled hypercholesterolemia (defined as fasting cholesterol > 300 mg/dL OR > 7.75 mmol/L) or hypertriglyceridemia (defined as fasting triglycerides > 2.5 x ULN), despite optimal medical therapy -
• No known active hepatitis B (defined as hepatitis B surface antigen [HbsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) Patients with human immunodeficiency virus (HIV) positivity are allowed if CD4 count > 500 cells/uL.
• No known active or uncontrolled infections requiring ongoing antifungals or antibiotics in the 3 days prior to registration.
• No receipt of live attenuated vaccines in the 7 days prior to registration.
• No known liver cirrhosis.
• No known prior drug-induced pneumonitis that was symptomatic or required treatment
• No known medical condition causing an inability to swallow and no known impairment of gastrointestinal function that may significantly alter the absorption of an oral agent.
• No known hypersensitivity to everolimus or other rapamycin analogs (e.g., sirolimus, temsirolimus, etc.).
• Concurrent somatostatin analog use while on protocol therapy is allowed provided that the patient:
  • has a functional tumor (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome);
  • has been on a stable dose of somatostatin analog therapy for at least three months;
  • has previously demonstrated radiographic disease progression while on somatostatin analog therapy. For subjects receiving lutetium Lu 177 dotatate, there should be a minimum of 14 days between long-acting somatostatin analogue and lutetium Lu 177 dotatate dosing. Short-acting somatostatin analogs should not be administered within 24 hours of lutetium Lu 177 dotatate dosing. Following lutetium Lu 177 dotatate dosing, long-acting somatostatin analogs may be administered between 4 and 24 hours after each dose.
• Chronic concomitant treatment with strong inhibitors or inducers of CYP3A4 is not allowed on this study. Patients on strong inhibitors or inducers of CYP3A4 must discontinue the drug(s) 7 days prior to registration.
• Chronic concomitant treatment with strong inhibitors or inducers of P-glycoprotein (PgP) is not allowed on this study. Patients on strong inhibitors or inducers of PgP must discontinue the drug(s) 7 days prior to registration.

RE-REGISTRATION:

• Confirmation of disease progression by RECIST v1.1 by real-time Alliance ICL at IROC Ohio central radiographic review.
• Not pregnant and not nursing.
• Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 14 days prior to re-registration is required.
• ECOG performance status 0-2.
• Hemoglobin ≥ 8.0 g/dL.
• Platelet count ≥ 75,000/mm^3.
• Absolute neutrophil count (ANC) ≥ 1,500/mm^3.
• Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance ≥ 40 mL/min.
• Calculated by the Cockcroft-Gault equation.
• Total bilirubin ≤ 2.0 x ULN.
• In patients with Gilbert's syndrome, if total bilirubin is > 2.0 x ULN, then direct bilirubin must be ≤ 2.0 x ULN.
• Albumin ≥ 2.8 g/dL.
• AST/ALT ≤ 3.0 x ULN.

Eligibility last updated 1/17/22. Questions regarding updates should be directed to the study team contact.

• Individuals ≥ 18 years of age.
• False positive HIV 2 test with a positive or indeterminate HIV2 antibody test and negative PCR testing.
• Must have been seen in the Mayo Clinic Infectious Disease/HIV Clinic

• Individuals < 18 years of age.

Clinician participants are eligible to be included in the study only if all of the following criteria apply:

• Employed as a Community Pediatric and Adolescent Medicine clinician (consultant or nurse practitioner) at MCR downtown or MCHS Albert Lea/Austin/Red Wing.
• Able to provide written consent.
• Are willing to follow recommendations to schedule/see participant and their caregiver for regular asthma follow-up care every 3-6 months.
  • Note: Asthma care coordinators who are involved in the usual care of the pediatric participant will also be included in the study.

Pediatric participants are eligible to be included in the study only if all of the following criteria apply:

• Ages 6-17 years old with diagnosis of asthma.
• Have a caregiver who is willing to participate alongside pediatric participant and to have regular asthma follow-up care every 3-6 months.
• Adolescent participants ages 13-17 years and their caregivers are able to give written informed consent; or child participants ages 8-12 years are able to provide assent and their caregivers are able to give written informed consent.
• Both participant and caregiver are able to read and write in English.
• Receive pediatric primary care at MCR or MCHS from participating study clinician.
• Access for caregiver and/or adolescent participants to an Android or iPhone with Wi-Fi access and availability for at least monthly use.
• Active asthma defined by at least one clinic visit with a diagnosis of asthma per Mayo EHR or on active asthma control or rescue medication in the past 12 months. Priority will be given to those with persistent asthma on inhaled corticosteroids therapy or those with poorly controlled asthma defined by any of the following criteria in the past 12 months, except item v (past 2-week period);
  • Asthma Control Test15 for adolescents ≥ 12 years or Childhood Asthma Control Test16 for children < 12 years (score< 20);
  • ED visit for asthma; or
  • Hospitalization for asthma; or
  • Unscheduled outpatient visit for asthma requiring oral corticosteroid use; or
  • Asthma symptoms at the screening interview, including 1) more than 2 days per week shortness of breath, wheezing, chest tightness, or 2) more than 1 night awakening due to asthma in the past 2-week period.
• Participant had their latest asthma follow-up visit more than 3 months prior to the screening date of the study.

Pediatric participants who do not meet the eligibility criteria described above will be excluded and those will be excluded from the study if any of the following criteria apply:

• Major medical problems prohibiting study participation and inability to perform study procedures (including spirometry); suspected symptoms of exercise-induced laryngeal obstruction (EILO), tracheobronchial foreign body at or about the incidence date of asthma, wheezing occurring only in response to anesthesia or medications, bullous emphysema or pulmonary fibrosis on chest radiograph, PiZZ alpha1-antitrypsin, cystic fibrosis, or other major chest disease such as severe kyphoscoliosis or bronchiectasis.
• Pediatric participant pregnancy.
• Hyposensitization therapy for > 3 months prior to study enrollment.
• Participation in any other interventional studies for asthma within 1 month prior to study.

Eligibility last updated 2/8/22. Questions regarding updates should be directed to the study team contact.

• Informed consent/assent provided by the participant and/or participant's or legally authorized representative.
• Biopsy proven AA amyloidosis.
• Measurable disease.
• Ability to travel to the study site and adhere to study-related follow-up examinations and/or procedures and provide access to participant’s medical records.

• Participant has any condition that in the opinion of the Site Investigator, would ultimately prevent the completion of study procedures.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 3/17/23. Questions regarding updates should be directed to the study team contact

• Diagnosis of clinical stage IIIB and IIIC (AJCC v7) metastatic melanoma, eligible for complete surgical resection of all metastases (surgically resectable).
• Eligible subjects must have measurable disease and must be candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm.
• Males or females, age ≥ 18 years.
• ECOG Performance Status/WHO Performance Status ≤ 1.
• Life expectancy of > 24 months.
• Absolute neutrophil count > 1.5 x 10^9/L.
• Hemoglobin > 9.0 g/dL.
• Platelets > 100 x 10^9/L.
• Total bilirubin ≤ 30 µmol/L (or ≤ 2.0 mg/dl).
• ALT and AST ≤ 2.5 x the upper limit of normal (ULN).
• Serum creatinine < 1.5 x ULN .
• LDH serum level ≤ 1.5 x ULN.
• Documented negative test for HIV, HBV and HCV. For HBV serology, the determination of HBsAg, and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV negative serum HBV-DNA is also required.
• All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.03) Grade ≤ 1 unless otherwise specified above.
• All women of childbearing potential (WOCBP) must have negative pregnancy test results at the screening. WOCBP must be using, from the screening to three months following the last study drug administration, highly effective contraception methods. WOCBP and effective contraception methods are defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomized partner or sexual abstinence.  Pregnancy test will be repeated at the safety visit (only WOCBP and only for patients in Arm 1).
• Male patients with WOCBP partners must agree to use simultaneously two acceptable methods of contraception (i.e., spermicidal gel plus condom) from the screening to three months following the last study drug administration.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

• Uveal melanoma or mucosal melanoma
• Evidence of distant metastases at screening.
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except: cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1), second primary melanoma in situ or any cancer curatively treated ≥ 5 years prior to study entry.
• Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
• History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
• Inadequately controlled cardiac arrhythmias including atrial fibrillation.
• Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).
• LVEF ≤ 50% and/or abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator.
• Uncontrolled hypertension.
• Ischemic peripheral vascular disease (Grade IIb-IV).
• Severe diabetic retinopathy.
• Active autoimmune disease.
• History of organ allograft or stem cell transplantation.
• Recovery from major trauma including surgery within 4 weeks prior to enrollment.
• Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies or any other constituent of the product.
• Breast feeding female.
• Anti-tumor therapy (except small surgery) within 4 weeks before enrollment.
• Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before enrollment.
• Planned administration of growth factors or immunomodulatory agents within 7 days before enrollment.
• Patient requiring or taking corticosteroids or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion.
• Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
• Previous enrolment and randomization in the same study.

Eligibility last updated to match clinicaltrials.gov 3/8/23. Questions regarding updates should be directed to the study team contact.

• Confirmed diagnosis of SCFE.
• Intend to receiving follow-up at participating centre.
• Less than 18 years old at time of admission.
• Adequate diagnostic information and radiographic imaging (for patients previously treated for SCFE).

• No definitive diagnosis of SCFE.
• Do not intend to receive follow-up at a participating centre.
• Greater than 18 years old at time of admission.
• Prior treatment for SCFE not appropriately documented.
• Known or suspected underlying conditions (e.g., cerebral palsy, spina bifida, or osteogenesis imperfecta)

Eligibility last updated 8/18/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Pre-registration: 

• Age ≥ 18 years.
• Disease characteristics.
• Histological confirmation of adenocarcinoma of the stomach or gastroesophageal junction (GEJ).
• Currently receiving first-line therapy with FOLFOX and nivolumab without evidence of disease progression OR planning to start first-line therapy with FOLFOX and nivolumab.
• No radiographic or histological evidence of non-peritoneal metastasis.
• ECOG Performance Status (PS) 0, 1 or 2.
• Willingness to provide mandatory blood specimens for correlative research.
• Willingness to provide mandatory tissue specimens for correlative research.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).

Inclusion Criteria
•Registration:

• Peritoneal Carcinomatosis Index (PCI) ≥ 1 and ≤ 24 obtained ≤ 30 days prior to registration.
• Clinical, pathological, or radiographic evidence of peritoneal metastasis per PCI (Appendix II) and PGRS.
• The following laboratory values obtained ≤ 15 days prior to registration:
• • Hemoglobin ≥ 8.0 g/dL;
  • Absolute neutrophil count (ANC) ≥ 1000/mm^3;
  • Platelet count ≥ 75,000/mm^3;
  • Total bilirubin ≤ 1.5 x ULN;
  • Alanine aminotransferase (ALT) AND aspartate transaminase (AST) ≤ 1.5 x ULN;
  • PT/INR/aPTT ≤ 1.5 x ULN;
    OR if patient is receiving anticoagulant therapy, then INR or aPTT is within target range of therapy;
• • Calculated creatinine clearance ≥ 45 ml/min using the Cockcroft-Gault formula below:
    • Creatinine clearance for males = (140-age) (weight in kg) (72) (serum creatinine inmgdL);
    • Creatinine clearance for females = (140-age) (weight in kg) (0.85 )(72)(serum creatinine inmgdL).
• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only.
• Provide written informed consent.
• Willingness to provide mandatory blood specimens for correlative research.
• Willingness to provide mandatory tissue specimens for correlative research.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).

Exclusion Criteria
•Pre-registration:

• Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects:
• • Pregnant persons;
  • Nursing persons;
  • Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception.
• Any of the following prior therapies: IL-2 or chronic corticosteroids, or immunosuppressive agents:
  • NOTE: Inhaled corticosteroids are allowed.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy.
• Uncontrolled intercurrent illness including, but not limited to:
• • Ongoing or active infection;
  • Symptomatic congestive heart failure;
  • Unstable angina pectoris;
  • Cardiac arrhythmia;
  • Psychiatric illness/social situations that would limit compliance with study requirements;
  • Autoimmune disease.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Active second malignancy currently receiving systemic treatment ≤ 6 months prior to pre-registration.
• History of myocardial infarction ≤ 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.

Exclusion Criteria
•Registration:

• Identification of non-peritoneal metastasis during laparoscopy.
• Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects:
• • Pregnant persons;
  • Nursing persons;
  • Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception.
• Any of the following therapies: prior immune checkpoint inhibitors, prior IL-2, or chronic corticosteroids or immunosuppressive agents:
  • NOTE: Inhaled corticosteroids are allowed. One-time antiemetic dose is allowed.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy.
• Uncontrolled intercurrent illness including, but not limited to:
• • Ongoing or active infection;
  • Symptomatic congestive heart failure;
  • Unstable angina pectoris;
  • Cardiac arrhythmia;
  • Psychiatric illness/social situations (e.g., substance abuse) that would limit compliance with study requirements;
  • Autoimmune disease requiring systemic treatment;
  • Small bowel obstruction.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Active malignancy currently receiving systemic treatment ≤ 6 months prior to registration.
• History of myocardial infarction ≤ 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
• Small bowel obstruction < 15 days prior to registration.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/31/23. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years
• Radiographic evidence or histopathologic confirmation of CNS malignancy, with or without prior resection. 
• Provide written informed consent for the current study.
• Willing to undergo at least one MRI (at most two) with proton and/or phosphorus magnetic resonance spectroscopy analysis.

• Vulnerable populations:  pregnant or nursing women (Arm B exempt), prisoners, mentally handicapped.
• Cardiac pacemaker or artificial heart valve.
• Metal plate, pin, or other metallic implant.
• Intrauterine device, such as Copper-7 IUD.
• Insulin or other drug pump.
• Non-titanium aneurysm clips.
• Previous gunshot wound.
• Cochlear implant or other hearing device.
• Employment history as a metalworker (had metal in eye).
• Permanent (tattoo) eye-liner.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 11/16/23. Questions regarding updates should be directed to the study team contact.

Stricturing CD Participant Criteria

Inclusion Criteria

• Male or nonpregnant, nonlactating females, 16 to 80 years of age at the time of the SOC MRE.
• An established diagnosis of CD by a gastroenterologist[BDHM1] [FJGM2] .
• Documented symptomatic stricturing small bowel CD in reach of colonoscopy (i.e., a portion of the stricture is located within 15 cm of the ileocecal valve anastomosis).
• Anastomotic or naïve small bowel CD stricture(s) at the time of  clinically-indicated CT entergraphy (CTE[FJGM3] ) or MRE, where naïve small bowel stricture is defined by the combination of:
  • localized luminal narrowing (luminal diameter reduction of at least 50% relative to normal adjacent bowel loop);  AND
  • bowel wall thickening (25% increase relative to adjacent unaffected bowel); AND
  • either: maximum associated small bowel dilation (luminal diameter greater than 3 cm) OR inability to pass an adult or pediatric colonoscope through the narrowed area prior to dilation and unequivocal proximal small bowel dilation (but may be less than 3 cm[FJGM4] ). Endoscopic diagnosis of stricture should be within 6 months of MRE.
• An anastomotic stricture is defined the same as a naïve stricture, but at the site of prior intestinal resection with anastomosis.
• Clinical symptoms consistent with obstruction defined by the S-PRO items including abdominal pain after eating (at least often) and dietary restrictions (at least moderate) within 1 month of the SOC MRE[BDHM5] [FJGM6]  or CTE.
• Radiologically confirmed CD stricture (CONSTRICT criteria)1 as determined by SOC MRE or CTE performed according to accepted technical parameters [refs].
• Surgical resection (Aim 1) or SOC endoscopy (Aim 2) of the small bowel stricture scheduled to occur within 3 months of the research MRE.

Exclusion Criteria

• Internal penetrating disease as shown by fistula, abscess, or inflammatory mass (phlegmon)[FJGM7] . A blind-ending sinus is not excluded.
• Gastrointestinal malignancies.
• More than 2 distal ileal strictures at the time of SOC MRE or CTE (where a long segment with multiple areas of narrowing with confluent inflammation between them is counted as 1 stricture, and 2 strictures within 3 cm are counted as a single stricture).
• A terminal ileal stricture in a patient with end ileostomy, where the stricture is confined within the subcutaneous tissues and does not extend intra-abdominally.
• A diverting loop ileostomy proximal to the dominant stricture.
• Total proctocolectomy with an ileoanal or Kock pouch.
• Stricturoplasty in the distal ileum, which is near or adjacent to a stricture[FJGM8].

UC Control Participant Criteria

Inclusion Criteria

• Male or nonpregnant, nonlactating females, 16 to 80 years of age.
• An established diagnosis of UC by a gastroenterologist and confirmed with endoscopy with histology and cross-sectional imaging.
• Patients with UC that have non-affected areas of the colon (e.g., left-sided colitis) are preferred since this would allow sampling of involved and non-involved segments in the same patient.
• Prior CTE or MRE showing absence of small bowel inflammation and perianal disease.

Exclusion Criteria

• Total proctocolectomy with an ileoanal or Kock pouch.
• Diverting loop ileostomy prior to colectomy.
• Completion proctectomies after prior segmental colon resection or presence of a Hartmann’s pouch.

Non-IBD Control Participant Criteria

Inclusion Criteria

• Male or nonpregnant, nonlactating females, 16 to 80 years of age.
• Patient undergoing colon or small bowel resection.
• Prior abdominopelvic CT or MRI showing lack of small bowel inflammation, segmental or diffuse colitis and perianal disease.

Exclusion Criteria

• Diagnosis of IBD.
• Total proctocolectomy with an ileoanal or Kock pouch.
• Diverting loop ileostomy upstream of resection.
• Ongoing chemotherapy or radiotherapy within 3 months of surgery.
• Completion proctectomies after prior segmental colon resection or presence of a Hartmann’s pouchy.
• Hereditary colorectal cancer (CRC) diagnosis. Sporadic cases of CRC are permitted to enroll.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/4/22. Questions regarding updates should be directed to the study team contact.

• Adults 18 to 65 years of age, inclusive.
• The completion of the following vaccinations at least 14 days prior to Visit 0:
  • COVID-19 vaccination series according to the current Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP); recommendations; and
  • At least one dose of the herpes zoster vaccination series; and
  • Current year seasonal influenza vaccine, if available.
• History of APS according to the updated 2006 Sapporo classification criteria, including at least one of the following within the prior 5 years:
  • Arterial thrombosis, except transient ischemic attack; or
  • Venous thrombosis, except superficial thrombophlebitis; or
  • Pregnancy morbidity, based on the updated 2006 Sapporo APS classification criteria; or
  • Microvascular APS, with at least one of the following:
    • Renal biopsy documentation of aPL-associated nephropathy; or
    • Lung biopsy or bronchoalveolar lavage documentation of diffuse alveolar hemorrhage (DAH); or
    • Skin biopsy documentation of livedoid vasculopathy.
• History of triple positive aPL within the prior 5 years and at least 12 weeks prior to enrollment, including all of the following:
  • aCL IgG level > Upper Limit of Normal (ULN); and
  • aβ2GPI IgG level > ULN; and
  • Positive LA test.
• Confirmation of triple positive aPL at screening, including all of the following:
  • aCL IgG level ≥ 40 GPL; and
  • aβ2GPI IgG level ≥ 40 SGU; and
  • Positive LA test.
• Willing and able to undergo anticoagulation with warfarin or low molecular weight heparin (LMWH), if there is a history of arterial or venous thrombosis.
• Willing and able to discontinue direct oral anticoagulants, including factor Xa inhibitors and direct thrombin inhibitors, if applicable.

• Inability or unwillingness to give written informed consent.
• Inability or unwillingness to comply with study protocol.
• Systemic autoimmune diseases other than APS, including but not limited to:
  • Systemic lupus erythematosus (SLE) meeting the EULAR/ACR criteria;
  • Rheumatoid arthritis meeting the ACR/EULAR classification criteria;
  • Small, medium, or large vessel vasculitis meeting ACR classification criteria.
• Catastrophic APS classification within the prior 90 days.
• Acute arterial or venous thrombosis within the prior 30 days.
• Use of the following medications:
  • Any prior treatment with CD38 targeting monoclonal antibodies, including daratumumab or isatuximab-irfc;
  • Administration of the Janssen COVID-19 vaccine within the prior 14 days;
  • The following within the prior 30 days:
    • Corticosteroids > 10 mg/day prednisone or equivalent;
    • Direct oral anticoagulants (DOACs);
    • Live attenuated vaccines;
    • IVIG.
  • Azathioprine, methotrexate, mycophenolate mofetil, mycophenolate sodium, lefluonomide, or calcineurin inhibitors within the prior 90 days;
  • Cyclophosphamide within the prior 90 days;
  • Immunomodulatory or immunosuppressive biologic agents, including belimumab, within the prior 90 days or 5 half-lives, whichever is greater;
  • Investigational agents within the prior 90 days or 5 half-lives, whichever is greater, except for COVID-19 vaccines and medications for prevention or treatment of COVID-19 per FDA Emergency Use Authorization (EUA);
  • Biologic B cell depleting agents including rituximab with either of the following:
    • Treatment within the prior 180 days; or
    • CD19+ absolute count < Lower Limit of Normal (LLN).
• Plasma exchange within the prior 90 days.
• Hemodialysis within the prior 90 days.
• Major surgical procedure within the prior 60 days.
• Known allergy, hypersensitivity, or intolerance to boron, malitol, sorbitol, corticosteroids, monoclonal antibodies including daratumumab, human proteins, or their excipients.
• Allergy, intolerance, or contraindication to acyclovir, valacyclovir, and famciclovir.
• Active or chronic infection, including the following:
  • Active bacterial, viral, fungal, or opportunistic infection;
  • Chronic infection requiring suppressive antibiotic treatment;
  • Intravenous antibiotics or hospitalization for infection within the prior 30 days;
  • Evidence of current or prior Mycobacterium tuberculosis infection (Section 8.3.3);
  • Human immunodeficiency virus (HIV);
  • Current or prior infection with hepatitis B virus (HBV);
  • Current or prior infection with hepatitis C virus (HCV), except adequately treated HCV with sustained virologic response ≥ 12 weeks;
  • Positive SARS-CoV-2 nucleic acid amplification test (NAAT) within the prior 14 days;
  • History of recurrent herpes zoster, or history of herpes zoster ophthalmicus, disseminated herpes zoster, or disseminated herpes simplex.
• The following laboratory abnormalities:
  • Absolute neutrophil count < 1500/mm^3;
  • Platelets < 100,000/mm^3 ;
  • Hemoglobin (Hgb) < 10 g/dL
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase > 2 x the Upper Limit of Normal (ULN);
  • Total bilirubin > 2 x ULN, except in the case of congenital bilirubinemia then direct bilirubin > 2 x ULN;
  • eGFR < 45 ml/min/1.73 m^2 .
• History of primary immunodeficiency.
• History of solid organ or hematopoietic stem cell transplantation.
• Comorbidities requiring systemic corticosteroid therapy, including those which have required three or more courses of systemic corticosteroids within the 12 months prior to Visit 0.
• Any of the following conditions with FEV1 < 70% predicted within the prior 90 days:
  • Asthma;
  • Chronic obstructive pulmonary disease (COPD);
  • DAH.
• Pulmonary hypertension.
• Poorly controlled diabetes mellitus, defined as hemoglobin A1c (HbA1c) ≥ 8.0%.
• Concomitant malignancy or history of malignancy, except adequately treated or excised nonmetastatic squamous cell carcinoma, basal cell skin carcinoma, or cervical carcinoma in situ.
• Clinically significant cardiac disease, including but not limited to:
  • Myocardial infarction within the prior 6 months; or
  • Unstable or uncontrolled disease or condition related to or affecting cardiac function, including but not limited to:
    • Unstable angina; or
    • Congestive heart failure, New York Heart Association Class II-IV; or
    • Uncontrolled cardiac arrhythmia.
• Current diagnosed mental illness or current diagnosed or self-reported drug or alcohol abuse which, in the opinion of the investigator, would interfere with the participant’s ability to comply with study requirements.
• Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, or neurological disease.
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant’s ability to comply with study requirements, or may impact the quality or interpretation of the data obtained from the study.
• Lack of peripheral venous access.
• Pregnancy, or planning a pregnancy during the 48 week study duration.
• Breast-feeding.
• Unwillingness to use medically acceptable non-prothrombotic contraception if of reproductive potential and engaging in sexual activity that could lead to pregnancy (Section 7.5).

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 9/19/23. Questions regarding updates should be directed to the study team contact.

• Adults aged 18-30 years.
• Have completed at least 12 years of school (i.e., completed through the junior year of high school).
• Currently or recently rostered on a junior, collegiate, semi-professional or professional sports team or individual sport that requires intense physical activity.

• Medical condition that would restrict strenuous physical activity – screened with the Screening for Eligibility Questionnaire.
• Regularly smokes or vapes (by self-report).

Eligibility last updated 12/29/22. Questions regarding updates should be directed to the study team contact.

• Adults aged 18-30 years.
• Have completed at least 12 years of school (i.e., completed through the junior year of high school).
• Currently or recently rostered on a junior, collegiate, semi-professional or professional sports team or individual sport that requires intense physical activity.

• Medical condition that would restrict strenuous physical activity – screened with the Screening for Eligibility Questionnaire.
• Regularly smokes or vapes (by self-report).

Eligibility last updated 12/29/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Pulmonary Arterial Hypertension (PAH) Subjects:

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
• Age ≥ 18 years at the time of signing informed consent.
• NYHA Class II-IV.
• LVEF ≥ 40 % within the preceding year.
• No hospitalizations due to heart failure in the preceding 30 days.
• No recent initiation of pulmonary vasodilator in the last 60 days.
• Pulmonary arterial hypertension by right heart catheterization (Mean PA pressure ≥ 20 mmHg with PVR > 2 Wood units) with no evidence of heart failure with preserved ejection fraction (exercise PCWP < 25 mm Hg).
• Symptomatic PAH patients with plan to undergo exercise RHC for reassessment of exertional symptoms.

Exclusion Criteria
•Pulmonary Arterial Hypertension (PAH) Subjects:

• Myocardial infarction, stroke, hospitalization for heart failure, unstable angina pectoris or transient ischemic attack within 30 days prior to the day of screening.
• Planned coronary, carotid, or peripheral artery revascularization.
• Any other condition judged by the investigator to be the primary cause of dyspnea (such as heart failure due to restrictive cardiomyopathy or infiltrative conditions (e.g., amyloidosis), hypertrophic obstructive cardiomyopathy, anemia, or more than moderate mitral or aortic heart valve disease).
• Wheelchair bound or orthopedic inability to exercise.
• Chronic hypoxemia with inability to exercise without oxygen supplementation.
• Skeletal muscle myopathy.
• History of rhabdomyolysis.
• Participation in any clinical trial of an approved or non-approved device for the treatment of pulmonary hypertension within 30 days before screening.
• Receipt of any investigational medicinal product within 30 days before screening.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
• Major surgery scheduled for the duration of the trial, affecting walking ability in the opinion of the investigator.
• Any disorder, including severe psychiatric disorder, suicidal behavior within 90 days before screening, and suspected drug abuse, which in the investigator´s opinion might jeopardize subject´s safety or compliance with the protocol.
• The criteria will be assessed at the investigator’s discretion unless otherwise stated.

Inclusion Criteria
•Healthy Controls:

Subjects are eligible to be included as controls for baseline assessment only if all the following inclusion criteria and none of the exclusion criteria apply. Patients must not have a known diagnosis of heart failure. Presence of other medical comorbidities is not an exclusion as long as there is no known diagnosis of heart failure, and there are no symptoms or signs of heart failure on evaluation at screening visit.

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
• Age ≥18 years at the time of signing informed consent.
• No known diagnosis of heart failure.

Exclusion Criteria
•Healthy Controls:

• Myocardial infarction, stroke, hospitalization for heart failure, unstable angina pectoris or transient ischemic attack within 30 days prior to the day of screening.
• Planned coronary, carotid, or peripheral artery revascularization.
• Any other condition judged by the investigator to contribute to abnormal effort tolerance (such as heart failure due to restrictive cardiomyopathy or infiltrative conditions (e.g., amyloidosis), hypertrophic obstructive cardiomyopathy, anemia, or more than moderate mitral or aortic heart valve disease).
• Wheelchair bound or orthopedic inability to exercise.
• Chronic hypoxemia with need for oxygen supplementation.
• Skeletal muscle myopathy.
• History of rhabdomyolysis.
• Participation in any clinical trial of an approved or non-approved device for the treatment of pulmonary hypertension within 30 days before screening.
• Receipt of any investigational medicinal product within 30 days before screening.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
• Major surgery scheduled for the duration of the study, affecting walking ability in the opinion of the investigator.
• Any disorder, including severe psychiatric disorder, suicidal behavior within 90 days before screening, and suspected drug abuse, which in the investigator´s opinion might jeopardize subject´s safety or compliance with the protocol.
• The criteria will be assessed at the investigator’s discretion unless otherwise stated.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/5/23. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 8/9/23. Questions regarding updates should be directed to the study team contact.

• Subjects over the age of 18 years.
• Ability of subject to provide written, informed consent.
• Patients with Chronic Liver Disease undergoing Transient Elastography (Fibroscan).

• Individuals under the age of 18.

Eligibility last updated 1/12/23. Questions regarding updates should be directed to the study team contact.

• Ages 14 to 65 years, inclusive, at the time of consent.
• Pathogenic or likely pathogenic Plakophilin 2 (PKP2) gene mutation.
• Diagnosed with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) and meet 2010 Modified Task Force Criteria for ARVC as affected.
• Functioning ICD.

• Currently receiving systemic immunosuppressive therapy, cytotoxic chemotherapy, immunoglobulin therapy, or monoclonal antibody therapy. 
• History of clinically significant liver disease, hepatitis B virus, hepatitis C virus, human immunodeficiency virus, or tuberculosis infection. 
• Previously dosed with any investigational or approved gene therapy product at any time. 
• Concurrent participation in another interventional clinical trial unless approved by the Sponsor. Participation in a noninterventional study may be allowed at the investigator’s discretion. 
• History of cardiac transplant.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 4/19/23. Questions regarding updates should be directed to the study team contact.

• Non-obese (BMI 20-25.0 kg/m^2) adults.
• 10 young (18-35y) and 10 older (65-80y) with both age groups balanced for sex (5F and 5M each).
• All subjects will not have cardiometabolic diseases (e.g., T2DM, HTN) and will not be taking anticoagulants, nor prescriptions or supplements that effect adipose tissue metabolism (i.e., statins, Thiazolidinediones, niacin, atypical antipsychotics, or fish oil).

• < 18 years of age.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 5/15/23. Questions regarding updates should be directed to the study team contact.

Inclusion Criiteria:

• AIAN person based on self-reported race/ethnicity.
• Gender identity as a woman.
• At least 18 years of age with no upper age limit.
• Resides in Minnesota.
• Meets criteria for OUD based on the DSM-5 Checklist (American Psychiatric Association, 2013).
• Self-reports at least one month of abstinence from opioid use based on TLFB interview and negative urine opiate screen.
• Current use of MOUD.
• Is comfortable speaking and reading English.
• Has an existing Facebook account or willing to set one up.
• Is willing and able to participate in the Facebook intervention for 3 months.
• Has access to broadband internet on a mobile phone/computer/tablet at any location.
• Is willing and able to travel to a community clinic in Minneapolis, Minnesota for the UDS.
• Provides written informed consent.
• No current suicidality.
• Has not participated in our formative work (Aim 1).

Exclusion Critiera:

• < 18 years of age. 

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 5/24/23. Questions regarding updates should be directed to the study team contact.

• Any ADPKD patient (ages 9-18 years) with confirmed ADPKD (via a combination of imaging, family history, and/or genetic testing), identified from existing and newly identified families for the proposed study.

• ADPKD patients with liver and or kidney transplant.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 5/23/23. Questions regarding updates should be directed to the study team contact.

• Individuals with constitutional MLH1 promoter hypermethylation who also have a blood relative with constitutional MLH1 promoter hypermethylation.
• Individuals without constitutional MLH1 promoter hypermethylation who have two or more blood relative with constitutional MLH1 promoter hypermethylation.
• 18 years of age and older.

• Individuals < 18 years of age.
• Individuals who neither have constitutional MLH1 promoter hypermethylation or family relatives with constitutional MLH1 promoter hypermethylation.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 6/13/23. Questions regarding updates should be directed to the study team contact.

• Adult donors aged 18 years and older.
• Donors who are scheduled for a clinically planned kidney donation surgical procedure at Brigham and Women’s Hospital or UT San Antonio Medical Center.
• Adult recipients aged 18 years and older
• Adult recipients who are scheduled for a clinically planned kidney transplant surgical procedure at Brigham and Women’s Hospital or UT San Antonio Medical Center.

• Adults on anticoagulants.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 5/16/23. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 6/15/23. Questions regarding updates should be directed to the study team contact.

Patients with acute PE will be eligible for participation in the study if:

• Acute PE < 24 hours from diagnosis.
• Signs of right heart strain:
  • Elevated troponin;
  • Elevated pro-BNP;
  • CT or echo evidence of right heart strain.

Patients with PE will be excluded when:

• Age <18 years of age.
• Known pulmonary hypertension from another condition (other than PE).
• Pulmonary emboli only involve the subsegmental vessels.
• Hypotension (systolic blood pressure < 80mmHg) or requiring vasopressors.
• Cardiac pacemaker present.
• PE occurred despite adequate anticoagulation (acute on chronic PE).
• History of pulmonary valve repair/replacement.
• Status post systemic or catheter-directed thrombolytic therapy for acute PE.
• Pregnant.

Healthy control patients (without PE).

• All exclusion criteria above would apply to the control population as well. Consented, healthy controls, will have Eko stethoscope recordings at rest and after exertion. Subjects will be asked to ascend 1-4 flights of stairs, based on the judgment of the participant and their level of activity, to elevate respiratory and heart rates. Exercise will be supervised by study personnel (nurse or physician).

• Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

  Eligibility last updated 7/24/23. Questions regarding updates should be directed to the study team contact.

• Provide written informed consent.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Age ≥ 18 years.
• Diagnosed with MACS:
  • At least 2 abnormal post-dexamethasone cortisol results:
    • 1 mg post-dexamethasone cortisol > 1.8 mcg/d;  or
    • 8 mg post-dexamethasone cortisol > 1 mcg/dL;
  • Historical dexamethasone suppression test results can be used if performed within 6 months prior to enrollment.
• Adrenal imaging phenotype consistent with benign disease (adrenal adenoma/s, macronodular or micronodular adrenal hyperplasia).
• At least one of the following comorbidities:
  • Obesity (BMI > 30 kg/m^2);
  • Dysglycemia;
  • Dyslipidemia;
  • Hypertension;
  • Osteopenia;
  • Osteoporosis;
  • Fragility fractures.
• Ability to take oral medication and be willing to adhere to the study intervention regimen.
• For females of reproductive potential: use of highly effective contraception initiated prior to baseline visit and for 1 month after completing metyrapone study.
• For persons of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of <5% per year during the treatment period and for 6 months after the last dose of study treatment.
• Stable timing for bedtime for at least one week prior to on-site study visits

• Planned alternative therapy for MACS within 6 months after joining the study.
• Current use of oral exogenous glucocorticoid therapy.
• Current use of opioid therapy > 20 MME/day.
• Planned use of oral exogenous glucocorticoid therapy.
• Planned use of opioid therapy > 20 MME/day.
• Use of injectable glucocorticoid within the last 6 weeks.
• Investigator’s judgement based on history/physical examination that a comorbidity or concomitant medication may impact the hypothalamic-pituitary-adrenal axis or steroid metabolome.
• Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection;
  • Symptomatic congestive heart failure;
  • Unstable angina pectoris;
  • Cardiac arrhythmia;
  • Psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnancy or lactation.
• Known allergic reactions to metyrapone.
• Suspected false positive post-dexamethasone cortisol results due to increased metabolism, poor absorption, or noncompliance with dexamethasone.
• Treatment with another investigational drug or other intervention within lower than specific therapy washout period.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 8/14/23. Questions regarding updates should be directed to the study team contact.

• 18 years of age and older.
• Patients undergoing left ventricular assist device implantation, heart transplantation, and donor hearts.

• Patients with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 8/15/23. Questions regarding updates should be directed to the study team contact.

• Adults > 18 years of age who have received fecal microbiota spores live bprk (VOWST) and fecal microbiota spores live-jslm (REBYOTA) for treatment of recurrent CDI.

• Pediatric patients, healthy individuals who have not received fecal microbiota spores live bprk (VOWST) and fecal microbiota spores live-jslm (REBYOTA) for treatment of recurrent CDI.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 8/15/23. Questions regarding updates should be directed to the study team contact.

• Individuals ≥ 18 years of age.
• Participants will be recruited from the Rochester Mayo Clinic Hospitals, from all units, excepting ICUs.
• Admission/Readmission to a medical hospital service.

Exclusion Criteria:

• Current admission to ICU.
• Under 18 years of age.
• Interpreter requirement.
• Acute intoxication.
• Aggressive/combative behavior.
• Sedation.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/25/23. Questions regarding updates should be directed to the study team contact.

1. Inclusion Criteria:

- Campylobacter PI-IBS defined by Rome III or Rome IV criteria

- Non IBS-C

- Moderate to severe symptoms defined by IBS-SSS≥175

- Able to safely undergo and consent to colonoscopy

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/18/23. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria - Group A Germline and Somatic Testing:

• Has Mayo Clinic medical record number.
• Confirmed cancer diagnosis which is either recurrent, relapsed, refractory, metastatic, or advanced.
• Participant aware of cancer diagnosis.
• Able to provide informed consent.
• ≥ 18 years old.
• Ability to provide blood, saliva, bone marrow aspirate or hair follicle sample.
• Ability to provide archived tissue.
  • NOTE: if tissue unavailable participant may still enroll onto the study for the germline collection.

• Individuals who have situations that would limit compliance with the study requirements.
• Institutionalized (i.e., Federal Medical Prison).
• Prior germline genetic testing with a 100+ multi-gene panel within the last 1 year of enrollment AND/OR
• Prior somatic tissue (250+ gene) testing within the prior 3 months of enrollment.
  • NOTE: Women, who are pregnant, or planning to become pregnant, can take part in this study.

Inclusion Criteria
•Group B Germline Testing Only:

• Has Mayo Clinic medical record number.
• Confirmed cancer diagnosis.
• Participant aware of cancer diagnosis.
• Able to provide informed consent.
• ≥ 18 years old.
• Ability to provide blood, saliva, or hair follicle sample.

• Individuals who have situations that would limit compliance with the study requirements.
• Institutionalized (i.e. Federal Medical Prison).
• Prior germline genetic testing with a 100+ multi-gene panel within the last 1 year of enrollment.

Eligibility last updated 12/28/23. Questions regarding updates should be directed to the study team contact.