• Have worked in the outpatient PPT setting at Mayo Clinic within the last 8 years (5 years for recent recall, plus 3 years to account for decreased patient population of interest during Covid-19 pandemic).
• Have worked with at least 1 Arabic speaking patient/family with interpreter services.
• Report ability to discuss experience with this patient population.

• Have not met inclusion criteria.

Eligibility last updated 10/17/22. Questions regarding updates should be directed to the study team contact.

• Clinical diagnosis of Cerebral Cavernous Angioma (CA).
• Age 18 or older.
• Solitary or multiple.
• Familial or sporadic.
• With or without prior symptoms.

• Prior excision of a solitary CA lesion.
• Prior stereotactic radiosurgery or any brain irradiation.
• Spinal cavernoma without brain lesion.
• Other brain pathology unrelated to CA (demyelinating disease, brain tumor).
• Seizures or stroke unrelated to CA in the prior year.
• Current pregnancy or within 6 months postpartum.
• Reluctance to undergo venipuncture or donate blood specimen, or be called for clinical follow-up for up to one year.

Eligibility last updated 9/2/21. Questions regarding updates should be directed to the study team contact.

• Willing and able to provide informed consent.
• First degree relatives (age 2.5 – 45 years) of T1D probands.
• Second and third degree relatives (age 2.5 – 20 years) of T1D probands: nieces, nephews, aunts, uncles, grandchildren, cousins, half-siblings.
• Individuals (age 2.5-45 years) who have diabetes-related autoantibodies potentially eligible for clinical trial.

• Have diabetes by 2011 ADA criteria.

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

Eligibility last updated8/24/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years.
• Ability to provide informed consent.
• Clinical suspicion of UGIB based on initial physical evaluation and intake history; e.g., prior episodes of UGI, presence of comorbid illnesses or medications associated with UGIB, laboratory data and symptom assessment, and patient is a candidate for endoscopy.

Exclusion  Criteria:

• Based on investigator’s assessment there is a clear need for urgent endoscopy or surgery at the time of consent.
• Known GI tract stricture.
• History of Zenker’s diverticulum and fistulas.
• Using a pacemaker or other implantable electrical device.
• Dysphagia or difficulties in swallowing pills the size of the capsule.
• History of achalasia or known esophageal dysmotility.
• History of gastroparesis.
• History of severe constipation (1 bowel movement per week or less).
• Currently taking medications intended for stimulation of GI motility.
• Patients that have had Upper GI barium study within the previous 24 hours.
• Currently pregnant or breastfeeding, or intend to become pregnant during the investigation.
• Presence of psychological issues preventing participation.
• Presence of known gastric bezoar.
• History of Crohn’s disease.
• History of small or large bowel obstruction.
• Suspected or previously diagnosed obstructing gastrointestinal tumor.
• Currently participating in another clinical trial that in the opinion of the investigator would interfere with the outcomes of this study or increase risk to the subject.
• Planned MRI investigation (MRI needed before the capsule is excreted).
• Presence of known hiatal hernia 5 cm or greater.
• Presence of known gastrointestinal abnormalities that could impact capsule performance.
• Presence of other concurrent conditions or known history that in the opinion of the Investigator would compromise patient safety or study objectives

Eligibility last updated 3/4/22. Questions regarding updates should be directed to the study team contact.

PREREGISTRATION (STEP 0) ELIGIBILITY CRITERIA
•INCLUSION

• Patient must be newly diagnosed with B-ALL or is suspected to have ALL.
• Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the presence of BCR-ABL translocation must be confirmed centrally. Patients can be registered and begin Step 1 therapy while awaiting central laboratory eligibility confirmation.
  • NOTE: Bone marrow and/or peripheral blood specimen must be submitted to the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patient's eligibility for registration to Step 1 or confirm patient evaluability. Centrally fluorescence-activated cell sorting (FACS) analysis will be performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of receipt of the specimen to the submitting institution. Bone marrow is to be from first pull (initial or re-direct). Specimens must contain sufficient blast cells. In cases where the bone marrow aspiration may be inadequate, or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood may be submitted, given that adequate circulating blasts are present (> 10%). If a diagnosis of BCR-ABL positive B-ALL has already been established by local Clinical Laboratory Improvement Act (CLIA) certified laboratories, the patient may be registered to Step 1 without waiting for central confirmation.
• Patients who started any kind of TKI prior to study registration are allowed to proceed on the study if they received no more than 14 days of TKI.

STEP 1 REGISTRATION INCLUSION ELIGIBILITY CRITERIA

• The diagnosis of Philadelphia chromosome positive (Ph+) ALL has been determined locally, and bone marrow and/or peripheral blood was sent for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center.
• Total bilirubin =< 3 mg/dL (unless related to Gilbert's syndrome in which case total bilirubin must be =< 5 mg/dL).
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X the institutional upper limit of normal (ULN).
• Estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation).
• Patients with acute organ dysfunction at registration, which may be attributed to leukemia can be registered regardless of lab results at presentation. Such patients will be allowed to register and can start Arm A steroid + TKI therapy but will only be allowed to proceed to Step 2 randomization if the eligibility criteria outlined is met.
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and if indicated, on treatment.
• Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better.
• Investigators must confirm which TKI patient is to receive.
  • NOTE: Patients with known T315I mutation status should receive ponatinib treatment.
  • NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during Step 1. The investigator must re-specify dasatinib or ponatinib prior to Step 2 randomization and from then on patients must receive the pre-selected TKI only.

STEP 2: RANDOMIZATION
•ELIGIBILITY CRITERIA
•INCLUSION

• Patient must have completed at least 7 of 21 days of protocol-treatment on Arm A prior to randomization.
  • NOTE: First day of steroids prescription after registration will be considered as the first day of study therapy. The selected TKI should be initiated prior to randomization.
• Patients who presented with acute organ dysfunction at Step 1 must have their total bilirubin and AST (SGOT)/ALT (SGPT) reduce to < 2 X institutional ULN and have an estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation).
• Investigators must confirm which TKI patient is to receive.
  • NOTE: Patients with known T315I mutation status should receive ponatinib treatment.
• For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization.

STEP 3: REGISTRATION (RE-INDUCTION) - ELIGIBILITY CRITERIA
•INCLUSION

• Institution has received centralized MRD results confirming positive status.
• Patients who presented with acute organ dysfunction must have their total bilirubin and AST (SGOT)/ALT (SGPT) reduce to < 2 X institutional ULN.
• Patients who presented with acute organ dysfunction must have an estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation).
• Investigators must confirm which TKI patient is to receive.
  • NOTE: Patients with known T315I mutation status should receive ponatinib treatment -For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined.

PREREGISTRATION (STEP 0) ELIGIBILITY CRITERIA
•EXCLUSION

• Patient must not have received chemotherapy for B-ALL.
• Patients who received up to five days of hydroxyurea or steroids of any kind with the aim to reduce disease burden prior to study registration are eligible.
• Patient must not have unstable epilepsy that requires treatment.

STEP 1 REGISTRATION ELIGIBILITY CRITERIA
•EXCLUSION

• Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
  • has achieved menarche at some point;
  • has not undergone a hysterectomy or bilateral oophorectomy; or
  • has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of registration, while on study treatment, and until at least six months after the last dose of study treatment.
• Patient must not have active concomitant malignancy. Patients on chronic hormonal therapy for breast or prostate cancer or patients treated with maintenance with targeted agents but are in remission with no evidence for the primary malignancies can be included.
• Patients must not have complaints of symptoms and/or have clinical and/or radiological signs that indicate an uncontrolled infection or any other concurrent medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol.

STEP 2: RANDOMIZATION
•ELIGIBILITY CRITERIA
•EXCLUSION

• Patient must not have active central nervous system (CNS) involvement by leukemic blasts. Patients with signs of CNS involvement at presentation are eligible for randomization if clearance of blasts from the cerebrospinal fluid (CSF) is demonstrated.

Eligibility last updated 2/9/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years.
• Able to provide written informed consent.
• Meets criteria as a High-Risk Individual as defined by protocol.

• Individuals less than 18 years.
• Individual who has a personal history of pancreatic ductal adenocarcinoma (PDAC).
• History of total pancreatectomy.

• Mayo Clinic patients.
• At least 18 years of age.
• Proficient in the English language.

• Inability to read (or lack of a support person to read to them) and lack of capacity to provide informed consent (and therefore lack of capacity to provide independent feedback on questionnaires, etc.).

Inclusion Criteria for Cohort 1:

Women will be ≥45 years of age and meet at least one of the following criteria:

- Abnormal uterine bleeding

- Postmenopausal bleeding

Exclusion Criteria for Cohort 1:

- Prior hysterectomy

- Current known pregnancy diagnosis

- Any prior pelvic or vaginal radiotherapy

- Any prior cancer (except basal cell skin cancer) within the past 5 years

- Chemotherapy within the past 5 years

- Current biopsy-proven cervical, vaginal, or vulvar cancer or lower genital tract
dysplasia

- Current biopsy-proven endometrial cancer or endometrial hyperplasia
•-

- Current biopsy-proven benign endometrial polyp

- Endometrial biopsy/sampling within the preceding 1 month showing benign endometrium

Inclusion Criteria for Cohort 2:

Women will be ≥18 years of age and meet at least one of the following criteria:

- Presence of biopsy-proven EC (any histology, including uterine carcinosarcoma) and
surgical intervention planned. Surgical intervention can include any of the following:
hysterectomy, D&C, hysteroscopic resection

- Biopsy showing AEH or EIN with surgical intervention planned. Surgical intervention
can include any of the following: hysterectomy, D&C, hysteroscopic resection, etc)

Exclusion Criteria for Cohort 2:

- Undergoing surgical procedure for recurrent or metastatic EC

- Receipt of preoperative neoadjuvant chemotherapy or radiotherapy for current EC
diagnosis

- Prior hysterectomy

- Current known pregnancy diagnosis

- Prior or current biopsy-proven cervical cancer

- Presence of concomitant biopsy-proven cervical dysplasia

- Any prior pelvic or vaginal radiotherapy

- Any prior cancer (except basal cell skin cancer) within the past 5 years

- Chemotherapy within the past 5 years

- Prior intervention or surgery with intent to completely remove the target pathology

Inclusion Criteria for Cohort 3:

Women will be ≥18 years of age, have a cervix and meet at least one of the following
criteria:

- History of current abnormal cervical/endocervical Pap test for which the patient is
presenting for colposcopy

- Cervical mass identified on physical exam and patient referred for cervical biopsy,
even if colposcopy not recommended or indicated

- Planned clinically indicated surgical excisional biopsy or removal of the cervix (cold
knife cone, LEEP, hysterectomy) for abnormal Pap test, cervical dysplasia, cervical
mass, or biopsy-proven invasive cervical cancer (adenocarcinoma, squamous cell
carcinoma, adenosquamous carcinoma, or less common primary cervical carcinomas all
eligible)

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

Eligibility last updated 11/15/22. Questions regarding updates should be directed to the study team contact.

• Symptomatic, moderate-to-severe or severe mitral regurgitation (MR ≥ Grade III per American Society of Echocardiography criteria), or severe mitral annular calcification (MAC), where a transcatheter therapy is deemed more appropriate than conventional mitral valve surgery by the local site heart team.
  • Note: MR severity must be determined by assessment of a qualifying transesophageal echocardiogram (TEE) and transthoracic echocardiogram (TTE), obtained within 120 days prior to subject consent, and must be confirmed by the Echocardiography Core Laboratory.
  • Note: Patients with severe MAC must have symptomatic mitral valve disease associated with MR ≥ Grade III, or severe mitral stenosis (MS), or both moderate MR and moderate MS as assessed by the Echocardiography Core Laboratory.
• NYHA Functional Classification ≥ II (if Class IV, patient must be ambulatory).
• The local site heart team determines that the subject has been adequately treated per applicable standards for coronary artery disease (e.g., revascularization), left ventricular dysfunction (e.g., cardiac resynchronization therapy) and heart failure (e.g., GDMT). The Subject Eligibility Committee must concur that the subject has been adequately treated.
• The local site heart team and the Subject Eligibility Committee concur on the intended study cohort for the subject.
  • Randomized Cohort: Eligibility for this cohort is limited to subjects where the local site heart team deems the mitral valve anatomy is amenable to transcatheter edge-to-edge repair within approved MitraClip indications. Subjects with primary MR must be at prohibitive surgical risk, while subjects with secondary MR must be symptomatic despite maximally-tolerated guideline- directed medical therapy.
  • Non-repairable Cohort: Eligibility for this cohort is limited to subjects where the local site heart team deems the mitral valve anatomy is not amenable for transcatheter repair with MitraClip or does not meet MitraClip indications.
  • Severe MAC Cohort: Eligibility for this cohort is limited to subjects where the local site heart team deems the degree of MAC renders the subject unsuitable for mitral valve surgery.
• Age 18 years or older at time of consent.
• Subject has been informed of the nature of the trial and agrees to its provisions, including the possibility of randomization to the Control group, complying with trial required testing, medications, and follow-up visits, and has provided written informed consent.

• Mitral valvular vegetation or mass.
• Left Ventricle (LV) or Left Atrium (LA) thrombus.
• Chest condition that prevents transapical access.
• Left Ventricular Ejection Fraction (LVEF) less than 25% assessed by the site based on a TTE obtained within 120 days prior to subject consent.
  • Note: LVEF will be principally based on TTE and must be confirmed by the Echocardiography Core Laboratory.
• Left Ventricular End Diastolic Diameter (LVEDD) > 7.0 cm assessed by the site based on a TTE obtained within 120 days prior to subject consent.
  • Note: A qualifying LVEDD must be confirmed by the Echocardiography Core Laboratory.
• Prior surgical or interventional treatment of mitral valve involving implantation of prosthetic material (e.g. valve repair or replacement, or MitraClip).
• Mitral pathoanatomy and Left Ventricular Outflow Tract (LVOT) anatomy deemed not suitable for Tendyne mitral valve implantation.
• Aortic valve disease requiring surgery or transcatheter intervention.
• Tricuspid valve disease requiring surgery or transcatheter intervention.
• Severe tricuspid regurgitation or severe right ventricular dysfunction.
• Any surgical or interventional procedure within the period of 60 days prior to or planned procedure 60 days following subject registration.
• Implant or revision of Cardiac Resynchronization Therapy (CRT) device within 90 days prior to intended subject registration.
• Myocardial Infarction (MI) within 30 days prior to intended subject registration.
• Symptomatic, unresolved multi-vessel or unprotected left main coronary artery disease (e.g., active ischemia) requiring stenting or Coronary Artery Bypass Grafting (CABG).
• Cerebrovascular accident (CVA) within 6 months prior to intended subject registration.
• Unresolved severe symptomatic carotid stenosis (> 70% by ultrasound).
• Cardiogenic shock or hemodynamic instability requiring inotropes or mechanical support devices at the time of planned implant procedure.
• Hypertrophic or restrictive cardiomyopathy, or constrictive pericarditis.
• Any of the following: leukopenia, acute anemia, thrombocytopenia, history of bleeding diathesis, or coagulopathy if cannot be adequately treated.
• History of endocarditis within 6 months of planned implant procedure.
• Active systemic infection requiring antibiotic therapy.
• Known hypersensitivity or contraindication to procedural or post- procedural medications (e.g., contrast solution, anti-coagulation and antiplatelet therapy) that cannot be adequately managed medically.
• Subjects in whom TEE is contraindicated or high risk.
• Known hypersensitivity to nickel or titanium.
• Subject is undergoing hemodialysis due to chronic renal failure.
• Subject has pulmonary arterial hypertension (fixed PAS > 70mmHg).
  • Note: If PAS > 70mmHg, site must provide documentation PAS is not fixed in order to be eligible.
• Subject has Chronic Obstructive Pulmonary Disease (COPD) requiring continuous home oxygen therapy or chronic outpatient oral steroid use.
• Subjects with non-cardiac comorbidities that are likely to result in a life expectancy of less than 12 months.
• Modified Rankin Scale ≥ 4 disability.
• Status 1 heart transplant or prior orthotopic heart transplantation.
• Pregnant, lactating, or planning pregnancy during the clinical investigation follow-up period.
  • Note: Female subjects of childbearing age should be instructed to use safe contraception (e.g. intrauterine devices, hormonal contraceptives: contraceptive pills, implants, transdermal patches hormonal vaginal devices, injections with prolonged release).
• Currently participating in an investigational drug or another device trial that has not reached its primary endpoint.
  • Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials.
• Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator’s opinion, could limit the subject’s ability to participate in the clinical investigation or to comply with follow- up requirements, or impact the scientific soundness of the clinical investigation results.

Eligibility last updated 4/28/22. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 6/8/22. Questions regarding updates should be directed to the study team contact.

PSC

• Patients diagnosed with Primary Sclerosing Cholangitis (PSC) between the age of 18 and 85.
• The diagnosis of PSC will be based on standard PSC criteria including clinical and biochemical evidence of chronic cholestasis of at least six months duration, positive cholangiographic findings and compatible liver biopsies if available.
• Women with PSC of childbearing potential and pregnant women will be offered enrollment because there is no risk to an unborn child in this investigation. Patients with PSC and Cholangiocarcinoma will be included.

Controls

• Controls without history of PSC or evidence of other chronic liver disease of either gender that will participate in this study should be between the ages of 18-85. 

• Patients unable to provide inform consent.
• Prisoners and institutionalized individuals.
• PSC with orthotopic  liver transplantation.
• History of Roux En Y procedure.

General

EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of HBV vaccination, do
not need to be testing for HBV DNA by PCR; Seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks
after completion of antiviral therapy).

Clinically significant cardiac disease, including: myocardial infarction within 6 months before randomization, or unstable or uncontrolled disease/condition related to or affection
cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV); Uncontrolled cardiac arrhythmia

Specific Exclusion Criteria [AMR Treatment Group]:

- Patients with biopsy evidence of grade 2R or 3R acute cell mediated rejection (CMR)

- Inability to give informed consent

Specific Exclusion Criteria [HLA Desensitization Group]:

- Patients listed for combined heart and liver transplantation will be excluded, as our unique experience with combined heart liver transplant (liver placed first), has demonstrated that in those cases high levels of circulating HLA antibodies may not increase the risk of hyperacute rejection.

- Seropositivity for human immunodeficiency virus (HIV)

- Seropositivity for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or
antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels.
Those who are PCR positive will be excluded.

EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic
marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.

- Seropositivity for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).

- Patients unable to give informed consent will also be excluded.

• Parent provision of consent.
• Student provision of assent.
• Enrollment in one of the 3rd grade classrooms at Gage Community Elementary School or the Rochester Public Schools elementary schools being surveyed.

• Students who do not assent to participate.
• Parents or legal guardian of students who do not consent to the study.

Eligibility last updated 8/25/21. Questions regarding updates should be directed to the study team contact.

• Patients with T2DM prior to transplant who are followed in our kidney transplant clinic at Mayo Clinic Rochester
• Age ≤ 70 at the time of transplant
• Positive C peptide (>2.0 ng/ml)at any time  and/or clinically verified T2DM
• Time post transplant 1- 4 years
• On insulin  ± other antihyperglycemic agents (study group N=15) and on single non-insulin based agent (control group N=15)
• 2 groups : BMI >35 kg/m2 (N=15) and <35 kg/m2 (N=15)

Exclusion Criteria:

• Patients on no anti-hyperglycemic treatment
• Unable to give a consent
• Non-english speaking, unable to fill the questionnaires

• Adult partipicipants, ≥ 18 years of age.
• Participants from the partnering African-American (AA) churches.

• Individuals less than 18 years of age.

• Age ≥ 18 years.
• Histological or cytological confirmation of brain tumor and/or suspected brain tumor based on clinical and radiologic findings.
• Prior chemotherapy and/or radiation treatment directed to the known/suspected tumor.
• Radiographic evidence of residual or previously unresected tumor.
• Willingness to undergo surgery and sign informed consent.
• Patients not currently eligible for an alternate competing interventional clinical trial.
• Enrollment in the Mayo Clinic Cancer Center Neuro-Oncology Program Registry for the study of Nervous System Tumors (IRB#12-003458)

• Age < 18 years.
• Prior gross total resection of brain tumor leading to absence of visible latent disease (exemption available for post-operative enrollment).
• Any contraindication to surgery, including anyone who in the opinion of the surgeon is at unreasonably elevated risk of wound complications.
• Avastin within the past 6 months for any reason.
• Patients who have not yet undergone surgery or radiation, but who would be appropriate candidates for an alternate interventional clinical trial (e.g., post-operative fractionated vs. single fraction radiation to the surgical cavity for surgical brain mets).

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

Eligibility last updated 12/20/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 10/12/22. Questions regarding updates should be directed to the study team contact.

• Patients coming to Mayo Clinic’s Genetic Heart Rhythm Clinic for evaluation or follow-up for their GHD.  
• Patients 18 years and older.

• Patient inability or unwillingness to participate in the study.
• Patients 17 years and under.

• Informed consent, or consent via legally authorized representative, if institutionally required for subjects with decompensated liver cirrhosis with current HE Grade 1 or 2, prior to any study-related procedures.
• Male or female patients age ≥ 18 years old.
• Cirrhosis of the liver.
• Patient has diuretic-resistant ascites, intractable ascites, or in the opinion of the Investigator, is unsuitable for treatment with an effective dose of diuretics for other reasons.
• Patients must have required in the 60-day period from the last LVP before consent, between 3 and 9 LVPs, including the last LVP on or before the day of consent.
• Dates for all LVPs occurring within 90 days prior to consent have been recorded. The volume of ascites removed at each of the LVPs must also have been recorded for the 90 days period prior to the last LVPs before consent.
• Serum creatinine (SCr) ≤ 2.00 mg/dL determined prior to randomization with value at randomization being less than 1.5 fold higher than value obtained at the screening visit.
• Women of child-bearing potential (e.g., not post-menopausal for at least one year or surgically sterile) must be neither pregnant nor lactating and must agree to use adequate birth control or be abstinent for the duration of the study.
• If patient is treated with beta blockers, dose has been stable for at least 30 days prior to randomization and may be maintained on that dose for the trial duration.
• If patient is treated with diuretics, patient has been on a stable daily dose for at least 10 days prior to consent.
• Willing and able to comply with trial instructions.

• Ascites with causes other than cirrhosis; such as cardiac or nephrogenic ascites or malignant ascites due to peritoneal carcinomatosis.
• Urinary sodium excretion > 100 mmol/day between day of consent and randomization.
• Total bilirubin > 5 mg/dL.
• Blood clotting International normalized ratio (INR) > 2.5.
• Platelet count ≤ 100,000/µL for the first eight patients enrolled. Eligibility of patients with a platelet count > 65,000 but < 100,000/µL should be confirmed with the Medical Monitor.
• Current or recent (within 3 months of consent) renal dialysis.
• Current or recent (within 1 month of consent) hepatic encephalopathy Grade 3 or 4 (WestHaven criteria).
• Superimposed acute liver failure/injury due to factors including acute alcoholic hepatitis, acute viral hepatitis, drugs, medications (e.g., acetaminophen), or other toxins (e.g., mushroom [Amanita] poisoning).
• History or presence of hepatic hydrothorax that has required a thoracentesis in the 7 days prior to randomization, or anticipated to require one within 7 days post-randomization, known pulmonary hypertension or a history of hepatopulmonary syndrome.
• Current or recent treatment (within 7 days of randomization) with octreotide, midodrine, vasopressin, dopamine or other vasopressors.
• Treatment with ACE inhibitors or ARBs 30 days prior to randomization.
• Current or recent (in the previous 60 days from consent) episode of respiratory failure requiring positive airway pressure (PAP) devices or intubation.
• Sepsis episode in the previous 28 days from consent.
• Episode of SBP within 14 days prior to consent. If a patient develops SBP in the pretreatment period randomization cannot occur for a minimum of 10 days and documented resolution of SBP.
• SBP at baseline visit (LVP -1).
• Episode of gastrointestinal hemorrhage (non-variceal) within 28 days prior to consent.
• Episode of bleeding esophageal varices within one week prior to consent.
• Ongoing documented or suspected infection.
• Severe cardiovascular disease that is a contraindication to terlipressin therapy such as a history of myocardial infarction, angina pectoris, advanced arteriosclerosis, uncontrolled cardiac arrhythmia, severe coronary insufficiency or uncontrolled hypertension.
• Findings suggestive of severe organic renal disease (severe proteinuria/hematuria, or abnormal renal ultrasound suggestive of obstructive renal pathology).
• Use of nephrotoxic drugs (e.g., aminoglycosides) in the 2 weeks before randomization
• Severe comorbidity that in the opinion of the Investigator would affect short-term prognosis and/or disallow safe participation in the trial (such as for example, severe anemia or pancytopenia, advanced progressive neoplasia such as hepatocellular carcinoma, unless eligible for transplant).
• Patients, who in the judgement of the Investigator, have been excessive alcohol drinkers in the past 12 weeks.
• Patient is in the opinion of the investigator, despite previous education on sodium restriction, anticipated to remain grossly non-compliant of sodium restricted diet.
• Recipient of renal or liver transplant.
• Implanted alfapump or previous recipient of alfapump that had pump removed within past 3 months
• Planned elective surgery related to cirrhosis complications, for example for hernia repair.
• Known allergy or hypersensitivity to terlipressin.
• Participation in other clinical research studies involving the treatment with other investigational drugs or evaluation with implantable devices within 30 days of consent.

Eligibility last updated 4/14/22.  Questions regarding updates should be directed to the study team contact.

• Men and women above 18 years of age.
• Diagnosed with POEMS syndrome (newly diagnosed or in remission) or with newly diagnosed multiple myeloma (MM) or with monoclonal gammopathy of undetermined significance (MGUS) or amyloid light-chain (AL) amyloidosis or healthy controls from their households.

• Age under 18 years
• Pregnancy
• Substance abuse
• Antibiotics use or gastrointestinal endoscopy in the 3 months prior to the study participation
• Chronic gastrointestinal disorder
• Gastrointestinal surgeries in the past 2 years  
• Chemotherapy (including anti-plasma cell treatment and steroids) or radiation treatment for cancer within the last 2 years or active cancer (other than plasma cell disorder)

Eligibility last updated6/9/22. Questions regarding updates should be directed to the study team contact.

• English-speaking patient (aged 18 or older).
• Has received dexamethasone either intravenously or as a prescription in the past 2 weeks. 
• Patients do not have to be experiencing hiccups at the time of contact, but it is anticipated that these patients will likely have recurrent symptoms based on further or episodic dexamethasone treatment. 
• Patients must currently be in an outpatient setting, as it is unlikely that an educational session would be relevant or of value to an inpatient.

• Individuals under 18 years of age.

• Ages 18 years of age or older.
• Patients with bleeding secondary to HHT, GAVE, SBA and OGIB.
• Age and sex matched patients without bleeding (controls).
• Patients willing to provide written informed consent.

• Unwillingness/unable to provide informed consent.

• Age ≥ 1 year(s) old (no maximum age).
• Radiologic appearance of diffuse midline glioma of the pons, including diffuse infiltration of ≥ 50% of the pons on MRI, with or without extension to the midbrain and/or medulla oblongata with at least 1 of the 3 brainstem symptoms (cranial nerve deficit, long tract sign, or cerebellar sign).
• If all features of this clinicoradiologic criteria are met, then patients can continue on protocol with or without a biopsy.
• If all features of this clinicoradiologic criteria are not met, patients must receive a brainstem lesion biopsy to be treated on protocol. If this cannot be completed, patients will be withdrawn from the study.
• If biopsy has already been completed at an outside institution, pathology must be reviewed at Mayo Clinic for trial enrollment.
• Able to undergo MRI Brain.
• Negative urine pregnancy test completed ≤ 7 days prior to registration, for women of childbearing potential only.
• Primary language of English or Spanish for patients and their caregiver.
• Patient or caregiver willing and able to provide written informed consent.
• Caregiver able to complete questionnaires by themselves or with assistance.
• Willing to return to enrolling institution for follow-up during the active monitoring phase of the study.

• Any patient who has received previous radiation to the brain.
• Any patient who has received previous chemotherapy.
• Any patient with a diagnosis of neurofibromatosis type 1 or 2 (NF1 or NF2).
• Any of the following:
  • Pregnant women;
  • Nursing women;
  • Women of childbearing potential who are unwilling to employ adequate contraception.
• 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.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Other active malignancy ≤ 5 years prior to registration.
  • EXCEPTIONS: Non-melanotic skin cancer, breast cancer, prostate cancer, well-differentiated thyroid cancer, carcinoma-in-situ of the cervix.
  • NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer.
• Patients > 16 years with an Eastern Cooperative Oncology Group (ECOG) score ≥ 4 and patients ≤ 16 years with a Lansky play scale ≤ 20.

Eligibility last updated 2/11/22. Questions regarding updates should be directed to the study team contact.

• Adults ≥ 18 years old.
• DLMP employees who work on-site at SDSC.
• Plan to complete the two dose SARS-CoV-2 vaccination schedule.

• Children < 18 years old.
• Subjects who have previously been diagnosed with SARS-CoV-2 infection.
• Subjects who test SARS-CoV-2 antibody positive on the pre-vaccination sample indicating prior infection.

• Adult participants (≥ 25 years of age).
• PLS diagnosis is based on the new PLS diagnostic criteria.
• Symptom onset was no more than 15 years prior to baseline.
• Ability to independently walk with or without an assistive device (e.g., walker) at the baseline evaluation.
• In cases where a molecular test has been done prior to enrollment in this study, HSP or HSP- related mutations are negative.
• Expected to have at least some bulbar symptoms (dysarthria, dysphagia, drooling or pseudobulbar affect); however, the absence of these symptoms will not exclude participants when molecular testing is negative for known HSP.
• UMN symptoms and signs in a region other than the legs.
• Normal brain and spinal cord neuroimaging except for changes expected for PLS.
• No active major neurological diseases other than PLS and no history of major neurological diseases.
• No major unstable medical diseases that require treatment (e.g., active cancer, dialysis) in the past 6 months.
• Participant is residing within a commutable distance to the study site and is willing to visit the study site as required.
• No history of ALS or PLS in immediate family and no family history of hereditary spastic paraplegia (HSP).
• gia (HSP) If disease duration is less than 5 years, no significant lower motor neuron (LMN) degeneration upon the EMG examination within 12 months before enrollment (evident entrapment neuropathy or radiculopathy are acceptable). If EMG tests were not done in this period, an EMG test should be obtained through regular patient care (through insurance) in order to make a diagnosis of PLS (this cost will not be covered by this research study). If disease duration is more than 5 years and at least one EMG was performed post-diagnosis, an EMG examination 12 months prior to enrollment is not required.
• Participant understands the study’s purpose, has capacity to consent, and is willing to sign the informed consent form.

• Unwilling or unable to give informed consent.
• UMN symptoms and signs only in the legs.
• Unwilling or unable to visit the study site as required.
• Clinically obvious cognitive impairment that precludes obtaining informed consent, as determined by the site PI.
• Participating in clinical treatment trials.

Eligibility last updated 5/3/22. Questions regarding updates should be directed to the study team contact.

• Subject is female.
• Subject has a BMI ≤ 29.
• Subject is between 18 and 80 years of age.
• Subject is a candidate for a unilateral or bilateral nipple sparing mastectomy procedure with mmediate reconstruction.
• Subject is at increased risk for breast cancer and is seeking prophylactic NSM surgery.
• Subject has no presence of occult cancer as confirmed by physical exam and by preoperative imaging per institution’s guidelines.  Known carriers of pathogenic BRCA1/2 mutations should have negative breast MRI.
• Subject has breast ptosis ≤ Grade 2.
• Subject has cup size ≤ C.
• Subject is at low to moderate risk for anesthesia (ASA class I, II or III).
• Subject is willing and able to provide written informed consent.
• Subject is willing and able to comply with the study protocol requirements including follow up examinations up to 5 years (+/- 90 days) post operatively.

• Subject has current or prior history of ipsilateral in-situ or invasive breast carcinoma.
• Subject has had previous breast surgery of the ipsilateral breast (excluding needle or core biopsies).
• Subject has an inflammatory and/or infectious skin condition and/or unhealed wounds on the ipsilateral breast.
• Subject has had chemotherapy for contralateral breast cancer within 3 weeks.
• Subject has had previous radiation treatment to the ipsilateral breast/chest area.
• Subject is planned to have other concomitant procedures (oophorectomy, hysterectomy, etc.).
• Subject has a current history of smoking or has smoked within 1 month of screening.
• Subject has hemoglobin A1C levels ≥ 8.
• Subject has a high risk for anesthesia (ASA class ≥ IV) or significant medical comorbidities (i.e., cardiac, pulmonary and neurologic) that preclude longer anesthesia times.
• Subject is contraindicated for general anesthesia or surgery.
• Subject has a known bleeding or clotting disorder.
• Subject is pregnant or suspected to be pregnant or is lactating.

• Unimpaired APOE e4/4 homozygotes age 65-75 and APOE e3/4 heterozygotes age 75-85 for the preclinical AD subset and age, sex, and education matched APOE e4 noncarriers for the unaffected controls. 
• Biomarker confirmation for preclinical diagnosis will be utilized to the extent possible (a subset of 130 members of our cohort have undergone amyloid-PET resulting in approximately 45 who are amyloid positive).

Exclusion Criteria:

• Previous stroke.
• Severe head injury.
• Craniotomy.
• Any other potentially confounding neurologic illness (typically anything that causes structural brain damage). 
• Psychoactive medication use will not be an absolute exclusionary criterion in patients with moderate to severe dementia but patients who are relatively drug-free will be prioritized to the extent they are available within the study period. 
• Psychoactive drug use will be exclusionary in the prospectively obtained clinical patients.

• Provide written informed consent from subjects, an impartial witness (for a subject who is physically unable to sign the informed consent form, but able to provide his/her consent by some other means [e.g., speaking, nodding, blinking]), or the subject’s legally authorized representative (LAR) (for a subject who lacks capacity to consent for him/herself [e.g., a subject without mental capacity to consent]), prior to beginning any study procedures.
• Cervical spinal cord injury who meet either of the following criteria:
  • AIS A with ISNCSCI neurological level of injury between C4 and C7 (for C4, the subject must have at least 1 point of motor activity within the ZPP inclusive of C5 to T1);
  • AIS B or C with ISNCSCI neurological level of injury between C4 and C7, and UEMS ≤ 28.
• Male and female subjects, age between 18 and 70 years at time of consent.
• Body mass index (BMI) < 40 kg/m^2.
• Acute traumatic spinal cord injury subjects who can receive MT-3921 as soon as possible after the injury, at least within 48 hours from the time of the injury.
• Willing and able to participate in all aspects of the study, including completion of subjective evaluations, attendance at scheduled clinic visits, and compliance with all protocol requirements as evidenced by providing informed consent.
• Both female and male subjects of childbearing potential must agree to use of contraception or abstinence during the study.

• Any concomitant injury that, in the judgement of the Investigator, interferes with the performance, interpretation or validity of neurological examinations (including fractures requiring casts), such as but not limited to multiple spinal cord lesions, brachial/lumbar plexus injury, cauda equina injury or traumatic brain injury defined by a Glasgow Coma Scale (GCS) <14 at time of examination.
• Poly-traumatic Injury as defined by Injury Severity Score (ISS) values > 25 at time of Screening.
• Penetrating spinal cord injuries.
• Complete transection of the spinal cord or spinal cord contusion size > 3 cm determined by MRI.
• Subjects who are highly anticipated to be dependent on long-term mechanical ventilation (e.g., beyond 10-14 days), which would interfere with study procedures including neurological exams.
• Any other significant pre-existing medical conditions prior to spinal cord injury or current conditions that, in the judgement of the Investigator, may increase the risks associated with study participation, and would preclude successful participation in the study.
• Subjects with history of active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV), except for adequately treated hepatitis B (HBV) and hepatitis C virus (HCV) with documentation of sustained virologic response defined as undetectable HCV RNA at least 12 weeks after the end of treatment.
• History of anaphylaxis or significant allergy to any food and medications.
• History or presence of malignancy within the last 3 years prior to screening, except subjects who have been treated successfully with no recurrence for >1 year of basal cell or squamous cell carcinoma of the skin or in-situ cervical cancer.
• Subjects with hereditary fructose intolerance.
• Psychoactive substance use disorder at any time during the 3 months preceding study entry (as defined by Diagnostic and Statistical Manual of Mental Disorders [DSM-5]).
• Participation in any clinical trial of a new chemical entity within 12 weeks prior to Screening.
• Pregnant or nursing women.