• Olmsted County residents ages 30+ are eligible to participate.

• Non-Olmsted County residents are not eligible.

• All patients who meet the diagnostic criteria for CVID  

• Infants below 6 months of age
• Subjects unable to provide a research blood sample for any medical reason             

1. Willing to give a blood sample
2. Ability to provide informed consent
3. Ability to complete all aspects of this trial
4. At least 18 years of age
5. Have cold agglutin disease with anemia

• None

Inclusion Criteria:

• Age ≥ 18 years.
• Diagnosis of RA fulfilling the ACR/EULAR 2010 classification criteria OR a diagnosis of UA suspected to be early RA with clinical synovitis of ≥ 1 joint and ≥ 1 other tender joint but not fulfilling classification criteria.
• Disease duration ≤ 6 months.
• Intention to start treatment with methotrexate (MTX).

Exclusion Criteria:

• Personal history of another definite autoimmune or inflammatory rheumatic disease (e.g., systemic lupus erythematosus, polymyositis, dermatomyositis, vasculitis, gout, or CPPD) diagnosed by a rheumatologist, excluding secondary Sjogren’s syndrome.
• Personal history of psoriasis diagnosed by a primary care physician or dermatologist.
• Personal history of inflammatory bowel disease diagnosed by a gastroenterologist.
• Unsuitability to participate in the judgment of a study investigator.
• Unwillingness or inability to return to Mayo Clinic for research follow-up visits.

• Subject or legally authorized representative provides written authorization and/or consent per institution and geographical requirements.
• Subject is intended to receive an eligible ISR product.
• Subject is at least 22 years of age.

• Subject is pregnant.
• Subject who is expected to be inaccessible for follow-up.
• Subject with exclusion criteria required by local law.
• Subject is currently enrolled in or plans to enroll in any concurrent drug and/or device study that may confound results (i.e. no required intervention that could affect interpretation of all-around product safety and or effectiveness).

• Adults age 18 years or older.
• Olmsted County residents at the time of survey.

• Pediatric population (age < 18 years old).
• Unwilling to participate or unable to consent.
• Known liver disease other than NAFLD at the time of survey.
• Pregnant women.

• Patients will be recruited who are undergoing MR Imaging studies as part of their routine clinical care for untreated intracranial aneurysms where no interventional treatment is planned.
• Consent to research.

• Unable to undergo MRI or have gadolinium (patients are already having these studies as part of routine clinical exam, so don’t foresee this being pertinent).
• Atypical cause of aneurysm (e.g. infectious, related to atrial myxoma, dissecting, etc.).
• Unable to remain still enough for diagnostic examinations.

• Any gender.
• Age over 4 years.
• Have read, understood and signed the approved informed consent form (parent or legal guardian must sign for anyone younger than 18 years).
• Willing to use the Seer EDS as instructed and provide feedback.

• Subjects considered by the participating site to be unable to operate the medical device due to cognitive or physical impairment.

Eligibility last updated 9/16/21.  Questions regarding updates should be directed to the study team contact.

• Patient with early onset coronary heart disease (CHD)/lipid disorders/other cardiovascular disease (CVD) with suspected/known genetic etiology referred from a clinical provider or found from screening for other research studies.
• Relatives of a patient with a CVD phenotype with suspected/known genetic etiology.

• None.

• Confirmed anhydramnios before 22 weeks GA for patients with FRF or confirmed diagnosis of CoBRA.
  • Anhydramnios in the absence of ruptured membranes (ROM) on ultrasound.
  • No significant bladder filling on ultrasound.
• Consent is signed and first therapeutic amnioinfusion can and does occur before 26 weeks and 0 days gestational age.
• Confirmation that the expectant mother does not wish to undergo termination of the pregnancy.
• Age ≥ 18 years of age for expectant mothers.
• Willingness to be followed and deliver at a RAFT center.
• Willingness for postnatal care to be performed at a RAFT center until discharge.
• Completed consults with Pediatric Nephrology, Neonatology, Transplant Surgery, Pediatric surgery, Maternal-Fetal Medicine Specialist, and Licensed Clinical Social Worker and a Genetic Counselor.

• Cervix less than 2.5 cm in length.
• No significant pathogenic or likely significant pathogenic findings on Karyotype or Microarray.
• Other significant congenital anomalies in the fetus.
• Evidence of chorioamnionitis or abruptio placentae.
• Evidence of rupture of membranes or chorioamniotic separation.
• Evidence of preterm labor.
• Multiple gestation.
• Severe maternal medical condition in pregnancy.
• Maternal depression as assessed by a Beck Depression Inventory score equal to or greater than 17 that is refractory to treatment.
• Technical limitations precluding amnioinfusion.

General Eligibility Criteria:

• Assessment for general eligibility criteria is based on medical records of the site and interview with a candidate patient. Patients must meet ALL general inclusion criteria to participate in the clinical investigation. If ANY general exclusion criteria are met, the patient is excluded from the clinical investigation and cannot be enrolled.
• If any clinical and/or laboratory tests are required for patient screening and are not included in a site’s standard tests, they must be completed after written informed consent is obtained.

• Subject must have at least one of the clinical indications before device implant in adherence with ACC/AHA/HRS/ESC dual chamber pacing guidelines.
• Subject is ≥ 18 years of age or age of legal consent, whichever age is greater.
• Subject has a life expectancy of at least one year.
• Subject is willing to comply with clinical investigation procedures and agrees to return to clinic for all required follow-up visits, tests, and exams.
• Subject has been informed of the nature of the clinical investigation, agrees to its provisions and has provided a signed written informed consent, approved by the IRB/EC.

• Subject is currently participating in another clinical investigation that may confound the results of this study as determined by the Sponsor.
• Subject is pregnant or nursing and those who plan pregnancy during the clinical investigation follow-up period.
• Subject has presence of anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator’s opinion, could confound the assessment of the investigational device and/or implant procedure, limit the subject’s ability to participate in the clinical investigation or to comply with follow-up requirements of the clinical investigation results.
• Subject has a known allergy or hypersensitivity to < 1 mg of dexamethasone sodium phosphate or any blood or tissue contacting material listed in the IFU.
• Subject has an implanted vena cava filter or mechanical tricuspid valve prosthesis.
• Subject has pre-existing, permanent endocardial pacing or defibrillation leads (does not include lead fragments).
• Subject has current implantation of either conventional or subcutaneous implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device.
• Subject has an implanted leadless cardiac pacemaker (except for an Aveir ventricular LP).
• Subject is implanted with an electrically-active implantable medical device with stimulation capabilities (such as neurological or cardiac stimulators)*.
• Subject is unable to read or write.
  • * NOTE:  Does not apply to a medical device with no known impact to the Aveir Leadless Pacemaker System, including the Aveir Link Module. Patient evaluation and the decision to implant the LP should take into account the presence of other active implantable devices and should include consultation with the Sponsor and/or manufacturer of the co-existing device.

Eligibility last updated 11/18/21. Questions regarding updates should be directed to the study team contact.

• Patient identified as having CLL or MBL, precursor condition to CLL and over the age of 18

• No diagnosis of CLL or MBL

• Adult patients, 18 years or older.
• Previous participation in an Astex-sponsored ASTX727 clinical trial (including, but not limited to studies ASTX727-01, ASTX727-02, and ASTX727-04) in which the subject was treated with ASTX727 and was still on active treatment with ASTX727 at the time of study completion as determined by Astex. 
• Subject is considered to be benefitting from ASTX727 treatment in the opinion of the treating investigator at the time of parent study completion (subjects must not be withdrawn from the parent study until eligibility for this study is confirmed). 
• Subject is able to understand and comply with the study procedures and understands the risks involved in the study. 
• Subject provides written informed consent before undergoing any study-specific procedure.
• Women of childbearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of childbearing potential must agree to practice 2 highly effective contraceptive methods of birth control and must agree not to become pregnant for 6 months after completing treatment; men with female partners of childbearing potential must agree to practice 2 highly effective contraceptive measures and must agree not to father a child while receiving ASTX727 and for at least 3 months after completing ASTX727 treatment.

• Any subject who, in the opinion of the investigator, may have other conditions, organ dysfunction, or for whom safety data from parent study participation suggests the risks of continuing treatment with ASTX727 may outweigh the benefits.

• KDIGO Stage 3 AKI, PCP @ Mayo Rochester.

• Patient with need for dialysis at discharge from hospital or hospice.
• Enrolled in the Primary Care Transition Program.
• Non-English speaking.
• Cognitive impairment.
• Dementia.

Inclusion Criteria
•For All Participants:

• Have completed the Week 24 visit of the feeder study.

Inclusion Criteria
•For Participants Assigned to the Open-label Treatment Cohort:

• Do not require immediate surgical intervention and is not planning corrective surgery/irradiation or medical therapy for TED during the course of the study.
• Did not permanently discontinue batoclimab.

Exclusion Criteria
•For All Participants:

• In the Investigator's judgement, the benefits of entry in the study do not outweigh the risk.

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

Eligibility last updated 9/30/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria

1. Males and females 12-17 years of age.
2. Residents of the United States.
3. Crohn's disease with single or multiple draining complex perianal fistulae (definition as below) for at least three months despite standard therapy (definition below).
4. Concurrent therapies with corticosteroids, 5-aminosalicylate (5-ASA) drugs, thiopurines, methotrexate (MTX), antibiotics, and anti-tumor necrosis factor (TNF) therapy are permitted.
5. All patients should have undergone a colonoscopy in last 12 months to rule out malignant or premalignant condition
6. Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
7. Ability to comply with protocol
8. Competent and able to provide written informed consent (and assent where appropriate).
9. Must have failed standard medical therapy including anti-TNF agents

Exclusion Criteria

1. Inability to obtain informed consent (and assent where appropriate).
2. Clinically significant medical conditions within the six months before administration of MSCs: e.g. sepsis, pneumonia active serious infection or other conditions that would, in the opinion of the investigators, compromise the safety of the patient.
3. Specific exclusions;
   1. Evidence of hepatitis B, C, or HIV
4. History of cancer including melanoma (with the exception of localized skin cancers)
5. Investigational drug within thirty (30) days of baseline
6. A resident outside the United States
7. Pregnant or trying to become pregnant, or breast feeding.
8. History of clinically significant auto-immunity (other than Crohn's disease) or any previous example of fat-directed autoimmunity
9. Previous allergic reaction to a perianal fistula plug.
10. If adipose tissue is not technically feasible
11. Weight less than 35 kg
12. Allergic to local anesthetics
13. Non-enterocutaneous tracts (i.e. recto-vaginal, entero-vesicular)

• Patients age ≥ 10 to < 22 with the diagnosis of adolescent idiopathic scoliosis being seen for scoliosis treatment (any skeletal maturity level, Risser 0-5).
• Curves > 35 degrees, < 70 degrees,
• Patient has consulted with a spine specialist regarding surgery of treatment of their scoliosis and surgery (fusion or non-fusion) has been considered, or the patient has undergone surgery for treatment of their scoliosis within the past three years.
• English speaking with parent/guardian present and willing to participate.
• Male and females.
• Patients < 3 years postop fusion and/or tether.

• None.

• Patients age ≥ 10 to < 22 with the diagnosis of adolescent idiopathic scoliosis being seen for scoliosis treatment (any skeletal maturity level, Risser 0-5).
• Curves > 35 degrees, < 70 degrees,
• Patient has consulted with a spine specialist regarding surgery of treatment of their scoliosis and surgery (fusion or non-fusion) has been considered, or the patient has undergone surgery for treatment of their scoliosis within the past three years.
• English speaking with parent/guardian present and willing to participate.
• Male and females.
• Patients < 3 years postop fusion and/or tether.

• None.

Patients presenting with an incipient clinical diagnosis for FSGS/MCD or MN or pediatric participants not previously biopsied, with a clinical diagnosis for FSGS/MCD or MN meeting the following inclusion criteria:

• Documented urinary protein excretion ≥500 mg/24 hours or spot protein: creatinine ratio equivalent at the time of diagnosis or within 3 months of the screening/eligibility visit.
• Scheduled renal biopsy

• Prior solid organ transplant
• A clinical diagnosis of glomerulopathy without diagnostic renal biopsy
• Clinical, serological or histological evidence of systemic lupus erythematosus (SLE) as defined by the ARA criteria. Patients with membranous in combination with SLE will be excluded because this entity is well defined within the International Society of Nephrology/Renal Pathology Society categories of lupus nephritis, and frequently overlaps with other classification categories of SLE nephritis (68)
• Clinical or histological evidence of other renal diseases (Alport, Nail Patella, Diabetic Nephropathy, IgA-nephritis, monoclonal gammopathy (multiple myelomas), genito-urinary malformations with vesico-urethral reflux or renal dysplasia)
• Known systemic disease diagnosis at time of enrollment with a life expectancy less than 6 months
• Unwillingness or inability to give a comprehensive informed consent
• Unwillingness to comply with study procedures and visit schedule
• Institutionalized individuals (e.g., prisoners)

• Consented participants in IRB study 489-04, Genetic Epidemiology of B-Cell Lymphoproliferative Disorders.
• History of MBL if not in study 489-04.

• Is unable to understand English and/or complete the informed consent form.

Eligibility last updated 8/20/21. Questions regarding updates should be directed to the study team contact.

• Current participant in the Mayo Clinic Biobank (08-007049, Cerhan PI), the Vascular Disease Biorepository (08-008355, Kullo PI), or the Study of the Genetic Determinants of Peripheral Artery Disease (PAD) (06-002911, Kullo PI) with blood derived DNA available
• Moderate to severe hypercholesterolemia, elevated triglycerides or colon polyps
• Age 0 to 70 years
• Resident of SE Minnesota area 
• Able to provide informed consent

Specific Aim 3 – Clinical Trial of FH

• Cases:
  • Proband with mutation in FH-related gene
    • First degree family member of above
• Age, sex and LDL-C matched Controls:
  • Proband with no mutation identified in FH related gene
    • First degree family member of above

• Pregnant women will be allowed to enroll in the study.  This is not an interventional study and there will be no risk to the mother or neonate.  Other vulnerable study populations will be excluded

Inclusion Criteria

• Study subjects with the glomerular diseases

1. Adults (18 years and up) Males and females
2. Diagnosed with an unruptured brain arteriovenous malformation (bAVM) at time of enrollment*
3. Willing and able to provide informed consent to participate in the study at enrollment * and be followed at one of the participating MARS Consortium Sites

Inclusion Criteria:

• An adult with any symptomatic disorder clinically diagnosed as Lewy Bodies, Parkinson disease dementia, Progressive Supranuclear Palsy, Multiple System Atrophy.

Exclusion Criteria: 

• An alternative diagnosis (including but not limited to: major head trauma, major psychiatric disorder, major systemic illness, substantial cerebrovascular disease) likely to be playing a substantial role in the manifestations of the parkinsonism.

Inclusion Criteria
•Cognitively Impaired (EOAD and EO-nonAD) Cohorts Only:

• Meets NIA-AA criteria for MCI due to AD or probable AD dementia.
• Have a global CDR score ≤ 1.0.
• Have capacity to provide informed consent (IC) or has a legal authorized representative or guardian who provides IC.
• Age between 40-64 years (inclusive) at the time of consent .
• Must have a study partner (informant) who spends a minimum average of 10 hours per week with the participant (e.g., family member, significant other, friend, caregiver) who is generally aware of the participants' daily activities and can provide information about the participant's cognitive and functional performance. If the participant does not have a study partner who spends 10 face-to-face hours per week, other arrangements for identifying a viable study partner will be granted on a case-by-case basis by the Site PI .
• Willing and able to complete longitudinal study procedures aside from LP which is an optional procedure.
• Not pregnant or lactating. Women must be two years post-menopausal, be surgically sterile, or have a negative pregnancy test prior to each PET scan.
• Fluent in English.

Inclusion Criteria
•Cognitively Normal (CN) Cohort Only:

• Meets criteria for cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living.
• Have a global CDR score = 0.
• Have capacity to provide informed consent.
• Have a Mini-Mental State Exam score between 26-30 (inclusive). Exceptions may be made for participant with less than 8 years of education at the discretion of the Site PI.
• Age between 40-64 years (inclusive) at the time of consent.
• Must have a study partner (informant) who spends a minimum average of 10 hours per week with the participant (e.g., family member, significant other, friend, caregiver) who is generally aware of the participants' daily activities and can provide information about the participant's cognitive and functional performance. If the participant does not have a study partner who spends 10 face-to-face hours per week, other arrangements for identifying a viable study partner will be granted on a case-by-case basis by the Site PI.
• Willing and able to complete longitudinal study procedures aside from LP which is an optional procedure.
• Not pregnant or lactating. Women must be two years post-menopausal, be surgically sterile, or have a negative pregnancy test prior to each PET scan.
• Fluent in English.

Exclusion Criteria
•All (EOAD, EO-nonAD and CN) Cohorts:

• Meets core clinical criteria for non-AD dementia.
• Two or more first degree relatives with a history of early-onset dementia suggestive of autosomal dominant transmission, unless known pathogenic mutations in APP, PSEN1, PSEN2 have been excluded.
• Known mutation in an ADAD gene (APP, PSEN1, PSEN2) or other autosomal dominant genes associated with other neurodegenerative disorders.
• Contraindications to 3T MRI (e.g., claustrophobia, pacemaker, select aneurismal clip, artificial heart valve, select ear implants, select stents incompatible with 3T MRI, metal fragments or foreign objects in the eyes, skin or body, etc.).
• Lifetime medical history of a brain disorder other than the disorder causing dementia except for headache (exceptions are allowed at the discretion of the Site PI
  •e.g., seizure disorder thought to be due to EOAD).
•  MRI scan with evidence of infection or focal lesions, cortical strokes, multiple lacunes (single lacune is allowable unless it meets criteria for strategic lacune affecting cognition).
• Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol (at the discretion of the Site PI).
• Medical radiation exposure will be assessed by the study physician. If the candidate participant has had more than one nuclear medicine study in the prior 12 months, study inclusion will require approval from the PET Core.
• Investigational agents are prohibited 30 days prior to entry.
• Previous enrollment in a therapeutic trial targeting amyloid or tau.
• Participation in other clinical studies with neuropsychological measures, with the exception of participants who are co-enrolled in the NACC Uniform Data Set (UDS) protocol (Note: This criterion is intended to reduce repeat measures effects during neuropsychological testing. Exceptions are allowed at the discretion of the Site PI).
• Lifetime history of schizophrenia spectrum disorders (DSM-5 criteria).
• Current history (in previous 12 months) of DSM-5 diagnosis of mania, bipolar disorder with or without psychotic features.
• Current history (in previous 6 months) of moderate or severe substance abuse (nicotine or caffeine is allowed).
• Suicidal behaviors in the past 12 months or active suicidal ideations.
• Residing in a 24-hour care skilled nursing facility (at the time of screening).
• History of torsades de pointes or taking medications known to prolong the QT interval.
• Corrected QT (QTc) interval ≥ 458 msec in males or ≥ 474 msec in females.
• For optional lumbar puncture procedure only:
  • Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be not clinically significant by the Site PI:
    • Platelet count <100,000/µl; 
    • INR>1.2;
    • Abnormal PT or PTT at screening.
  • Contraindications to the procedure, including but not limited to severe degenerative joint disease, deformity of the spine, history of a bleeding disorder. 
  • Suspected elevated intracranial pressure, Arnold Chiari malformation or mass lesion d. Use of the anticoagulant medications such as but not limited to warfarin, rivaroxaban, dabigatran.
• Deemed ineligible by the Site PI for any other reason.

• Ages 18 to 22 years old.

• Subjects outside the inclusion criteria age range.

• Patient has a Class I or IIa indication for implantation of an ICD according to the ACC/AHA/HRS Guidelines, or ESC guidelines. 
• Patient is at least 18 years of age and meets age requirements per local law. 
• Patient is geographically stable and willing and able to complete the study procedures and visits for the duration of the follow-up.

• Patient is unwilling or unable to personally provide Informed Consent. 
• Patient has indications for bradycardia pacing or Cardiac Resynchronization Therapy (CRT) (Class I, IIa, or IIb indication). 
• Patient with an existing pacemaker, ICD, or CRT device implant or leads. 
• Patients with these medical interventions are excluded from participation in the study: 
  • Prior sternotomy;
  • Any prior medical condition or procedure that leads to adhesions in the anterior mediastinal space (i.e., prior mediastinal instrumentation, mediastinitis);
  • Prior abdominal surgery in the epigastric region;
  • Planned sternotomy;
  • Prior chest radiotherapy Or any other prior/planned medical intervention not listed that precludes their participation in the opinion of the Investigator.
• Patient has previous pericarditis that:
  • Was chronic and recurrent; or
  • Resulted in pericardial effusion; or
  • Resulted in pericardial thickening or calcification. 
• Patients with these medical conditions or anatomies are excluded from participation in the study: 
  • Hiatal hernia that distorts mediastinal anatomy;
  • Marked sternal abnormality (e.g., pectus excavatum);
  • Decompensated heart failure;
  • COPD with oxygen dependence;
  • Gross hepatosplenomegaly.
• Or any other known medical condition or anatomy type not listed that precludes their participation in the opinion of the Investigator.
• Patients with a medical condition that precludes them from undergoing defibrillation testing: 
  • Severe aortic stenosis;
  • Intracardiac LA or LV thrombus;
  • Severe proximal three-vessel or left main coronary artery disease without revascularization;
  • Hemodynamic instability;
  • Unstable angina;
  • Recent stroke or transient ischemic attack (within the last 6 months);
  • Known inadequate external defibrillation; 
  • LVEF < 20%;
  • LVEDD > 70 mm.
• Or any other known medical condition not listed that precludes their participation in the opinion of the Investigator. 
• Patient with any evidence of active infection or undergoing treatment for an infection. 
• Patient is contraindicated from temporary suspension of oral/systemic anticoagulation.
• Patient with current implantation of neurostimulator or any other chronically implanted device that delivers current in the body. 
• Patient meets ACC/AHA/HRS or ESC clinical guideline Class III criteria for an ICD (e.g., life expectancy of less than 12 months). 
• Patient is enrolled or planning to enroll in a concurrent clinical study that may confound the results of this study, without documented pre-approval from a Medtronic study manager. 
• Patient with any exclusion criteria as required by local law (e.g., age or other).
• Pregnant women or breastfeeding women, or women of child bearing potential and who are not on a reliable form of birth regulation method or abstinence.

• Able and willing to provide written informed consent.
• Age ≥ 18 years of age.
• AFP lab result within past 180 days.
• All other lab results within past 90 days.
• Diagnosis HCC based on one of the following:
  • Histology (required if only one lesion < 2 cm is present) – Must have CT/MRI to calculate stage;
  • Two imaging tests, with at least one (CT/MRI/Angiography) within the past 3 months or up to 2 weeks after consent showing evidence of arterial hypervascularization, and the other within the past 6 months (US, CT, MRI/Angiography) indicating a mass in the liver.
• MELD < 15 OR INR is < 1.5, Total Bilirubin is < 1.7 and patient has a history of intrinsic renal disease.

• Prior or current therapeutic treatment of HCC.
• Cancer history within the last 5 years (excluding non-melanoma skin cancer).
• Participation in a treatment trial for HCC, before blood and data obtained.
• Undiagnosed liver mass.