Inclusion Criteria
•PAD Patients:

• Mild claudication to minor tissue loss (Rutherford 1-5).
• Resting or exercise ankle-brachial index < 0.9 or toe brachial index < 0.6.
• Age 35 or more.

Inclusion Criteria
•Healthy Volunteers:

• Age 35-90.

Exclusion Criteria
•PAD Patients and Healthy Volunteers: 

• Evidence of active infection.
• Chronic liver disease, end-stage renal disease (CKD 5), or chronic inflammatory disease.
• Poorly controlled diabetes (HbA1c > 8%).
• BMI < 18 or > 35.
• Recent other major surgery or illness within 30 days.
• Use of immunosuppresive medications or steroids.
• History of organ transplantation.
• Pregnancy, or plans to become pregnant, or lactating.

Exclusion Criteria - Healthy Volunteers:

• hsCRP > 2 mg/L.

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

Eligibility last updated 5/19/23. Questions regarding updates should be directed to the study team contact.

• ASA classification I to III, older than or equal to 18 years old.
• All genders.
• Presenting for primary total knee replacement for degenerative joint disease.
• Patient capable of providing their own informed consent.

• Vulnerable study populations including prisoners.
• Patients with a contralateral total knee arthroplasty < 2 years prior to the index procedure.
• Compromised health barring them from proceeding with surgery including acute or chronic kidney injury identified pre-operative.
• Patients unable to provide their own informed consent.
• Pregnancy.
• Patients with documented chronic pain syndromes.
• Patients with a history of prolonged daily opioids (more than 1 month) with an oral morphine equivalent of greater than 5mg/day.
• BMI > 45 kg/m^2.
• Allergies to any component of the study medications, including specific history of type 1 hypersensitivities to any NSAID.
• Patients with impaired cognitive function.
• Major systemic illnesses such as severe renal (estimated glomerular filtration rate less than 50ml/min), coronary artery disease requiring a bypass graft (CABG), other cardiac problems including congestive heart failure (CHF New York Heart Association class III to IV), or severe hepatic disorders defined as current or past diagnosis of acute/subacute liver necrosis, acute hepatic failure, chronic liver disease, liver abscess, hepatic coma, hepatorenal syndrome and other disorders of the liver.

Eligibility last updated 10/12/21. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 9/23/22. Questions regarding updates should be directed to the study team contact.

• Adult 21 years and older.
• English speaking.
• Able to provide consent.
• Clinically diagnosed stable heart failure with NYHA Class I-III symptoms.

• Patients who are unable to engage in a regularly structured exercise training program.
• History of dangerous arrhythmias.
• BMI > 40 kg/m^2
• Current smokers or smoking history of > 20 pack years
• Pregnant women, implanted pacemaker and/or ICD, cochlear implants, drug infusion pump, or any other implanted metal objects.

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

• Adults

• Standard exclusion criteria for clinical MRI; e.g. cardiac pacemaker, claustrophobia, an implanted device that has been determined to be MR conditional at 1.5T but not at 3T, anticipated considerable susceptibility artifact from hip prosthesis, etc.
• previous rectal surgery which may preclude tolerance of an endorectal coil

• All adult patients with at least moderate mx/ml-VHD and those with at least moderate single valve disease who had underwent a clinically indicated stress echocardiography study for their VHD prior to the date of IRB submission.
• All adult patients who would be scheduled for a clinically indicated stress echo study in the future (from the date of IRB submission, up to 31st Dec 2022).

• Patients < 18 years old

• Patient at Mayo Clinic – Rochester
• 18 years of age or older

• None

• Patients will be recruited if they already have MRI scans, DXA scans for bone mineral density, and radiographs of the lumbar spine within the last year.
• Three patient groups will be recruited; the first group includes twenty healthy patients with no history of spine disorders or low back pain. The second group includes twenty patients with symptomatic DD, according to the Pfirrmann grading system. The third group includes scoliotic patients (with deformity ≥ 15°).

• Individuals with prior spine, knee, or hip surgery within the last year will be excluded. Patients without imaging data will be excluded. Patients who are not able to perform the physical activities will be excluded. BMI ≥ 35.

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

Eligibility last updated 9/11/23. Questions regarding updates should be directed to the study team contact.

• At least 18 years of age.
• Previous diagnosis of type II diabetes mellitus on antihyperglycemics.
• Cell phone capable of uploading glycemic data through the Libre 3 app.
• Willing to give informed consent.

• Type I diabetes mellitus.
• Unable to return at 3 month evaluation.
• Unwillingness to provide informed consent.

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

Eligibility last updated 11/14/22. Questions regarding updates should be directed to the study team contact.

All Patients (Stages 2 and 3A):

1.            The patient is ≥18 years old.       

2.            The patient has a life expectancy of >6 months.               

3.            The patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.             

4.            The patient has adequate baseline organ function, including cardiac, renal, and hepatic function:

•             Left ventricular ejection fraction (LVEF) ≥ institutional lower limit of normal as measured by multigated acquisition scan (MUGA) or 2-dimensional (2-D) echocardiogram (ECHO) within 28 days prior to start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG).

•             Serum creatinine ≤1.5 mg/dL.

•             Serum albumin ≥3.2 g/dL (or ≥32 g/L) in the absence of receipt of IV albumin within the previous 72 hours.

•             Bilirubin ≤1.5 mg/dL.

•             Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 times the upper limit of normal (ULN).

•             Creatine phosphokinase (CPK) ≤2.5 times the ULN.

•             Absolute neutrophil count (ANC) ≥0.5 x 109/L.  

5.            If a woman of child-bearing potential (WOCBP), the patient has a negative serum or urine pregnancy test within 1 week prior to tagraxofusp treatment (intervals shorter than 1 week are acceptable, if required by institutional guidelines).       

6.            The patient (either male or female) agrees to use acceptable contraceptive methods for the duration of time in the study, and to continue to use acceptable contraceptive methods for 1 week after the last tagraxofusp infusion.                

7.            The patient has signed informed consent prior to initiation of any study-specific procedures or treatment.          

8.            The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for response assessments.                

 Additional Abbreviated Inclusion Criteria Specific to Patients with MF (Stage 2):

1.            Patient meets the 2016 WHO diagnostic criteria for MF and has an IPSS/DIPSS/DIPSS-plus intermediate-2 or high-risk disease. Patients with IPSS/DIPSS/DIPSS-plus low or intermediate-1 risk disease who have at least one of the following symptoms are also eligible: MF-related anemia (Hb <10 g/dL), splenomegaly (palpable size >10 cm), leukocytosis (WBC >25 x 109/L), marked thrombocytosis (platelet count >1000 x 109/L), or constitutional symptoms (weight loss >10%, during prior 6 months or fever [>37.5°C or drenching night sweats for >6 weeks]), as recommended by the ELN/IWG 2018 criteria (Barbui 2018).         

2.            Patient is approved JAK therapy (JAK1/JAK2 or JAK 2) resistant/refractory or intolerant, in accordance with the ELN/IWG 2018 criteria (Barbui 2018), and at least 4 weeks have elapsed between the last dose of any MF-directed drug treatments, excluding HU, and study enrollment (first dose). HU can be continued until 2 weeks prior to study enrollment.       

3.            Patient is not eligible for an immediate allogeneic stem cell transplantation (SCT).

Additional Abbreviated Inclusion Criteria Specific to Patients with CMML (Stage 3A):

1.            Patient has a 2016 WHO-defined diagnosis of CMML (persistent monocytosis ≥1x109/L for at least 3 months, with other causes excluded, and monocytes ≥10% of WBC in peripheral blood, no criteria and no previous history of CML, ET, PV, and acute promyelocytic leukemia; if eosinophilic, neither PDGFRA, PDGFRB, FGFR1 rearrangements nor PCM1-JAK2 translocation; <20% blasts in peripheral blood and bone marrow aspirate; >1 following criteria: dysplasia in >1 myeloid lineage, acquired clonal cytogenetic or molecular abnormality in hematopoietic cells).    

2.            Patient has 2016 WHO-defined CMML-1 (2-4% blasts in peripheral blood and/or 5-9% blasts in bone marrow) and CMML-2 (5-19% blasts in peripheral blood and/or 10-19% blasts in bone marrow, and/or presence of Auer rods) (Arber 2016).    

3.            Patient is refractory/resistant/intolerant, as defined for the purposes of this study (in the absence of a standard definition for CMML) below, to HMAs, or HU, or intensive chemotherapy, including:

•             Resistance/intolerance to HU is defined as:

o             Uncontrolled myeloproliferation, (platelets >400x109/L and WBC >10x109/L after 3 months of at least 2 g/day of HU); or

o             Myelosuppression at a clinically relevant dose; or

o             Presence of unacceptable HU-related non-hematological toxicities, such as mucocutaneous manifestations, gastrointestinal symptoms, pneumonitis or fever at any dose of HU.

Conventional definition for HMA failure is defined for the purposes of this study (in the absence of a standard definition for CMML) as:

o             Disease progression following at least 4 to 6 cycles of 5-azacitidine or decitabine; or

o             Relapse after achieving response; or

o             Intolerance to 5-azacitidine or decitabine at the prescribed dose.

OR

•             Patient is classified as high-risk based on the presence of morphological features, as described by the 2016 WHO prognostic system (Arber 2016), and the clinical and molecular features described in molecularly-integrated prognostic systems, such as the Groupe Français des Myélodysplasies (GFM), Mayo Molecular Model (MMM), and the CMML specific prognostic model (CPSS-Mol) (Woo 2020), and thus is not expected to benefit from HMAs.  

4.            Patient is ineligible for an immediate allogeneic stem cell transplantation (SCT).

All Patients (Stages 2 and 3A):

1.            Patient has persistent clinically significant toxicities Grade ≥2 from previous therapies, including cytotoxic chemotherapy, targeted therapies, biological therapies, or immunotherapies, not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue).      

2.            Patient has received treatment with any disease-related therapy, including radiation therapy within 14 days of study entry.      

3.            Patient has received an allo-SCT within 3 months of study entry.              

4.            Patient has received treatment with another investigational agent within 14 days of study entry or concurrent treatment with another investigational agent.  

5.            Patient has previously received treatment with tagraxofusp or has a known hypersensitivity to any components of the drug product.           

6.            Patient has an active malignancy and/or cancer history (excluding myeloproliferative disorders and concomitant myeloid malignancies as specified in the inclusion criteria) that can confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) and/or ongoing active malignancy or substantial potential for recurrence must be discussed with the Sponsor before study entry. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including superficial bladder cancer), cervical intraepithelial neoplasia, or organ-confined prostate cancer with no evidence of progressive disease.      

7.            Patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).     

8.            Patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator’s opinion, would put the patient at significant risk for pulmonary complications during the study.

9.            Patient has known active or suspected disease involvement of the central nervous system (CNS). If suspected due to clinical findings, CNS disease should be ruled out with relevant imaging and/or examination of cerebrospinal fluid.     

10.          Patient is receiving immunosuppressive therapy, with the exception of corticosteroids as specified in the inclusion criteria and tacrolimus, for treatment or prophylaxis of graft-versus-host disease (GVHD). If the patient has been on immunosuppressive treatment or prophylaxis for GVHD, the treatment(s) must have been discontinued at least 14 days prior to study drug and there must be no evidence of Grade ≥2 GVHD. 

11.          Patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness that would limit compliance with study requirements.     

12.          Patient is pregnant or breast feeding.   

13.          Patient has known human immunodeficiency virus (HIV).            

14.          Patient has evidence of active or chronic Hepatitis B or Hepatitis C infection.      

15.          Patient is oxygen-dependent.  

16.          Patient has any medical condition that in the Investigator’s opinion places the patient at an unacceptably high risk for toxicities.     

Additional Exclusion Criteria Specific to Patients with MF (Stage 2) apply.

1.            Patient has a platelet count <20x109/L and either a history of a recent or active bleed or known acquired von Willebrand disease.       

2.            Patient fulfills the 2016 WHO criteria defining leukemic transformation of MF (presence of peripheral blood or bone marrow blast count >20%).         

3.            Patient received splenic irradiation within 28 days prior to study entry.  

Additional Exclusion Criteria Specific to Patients with CMML (Stage 3A) apply.

1.            Patient requires corticosteroid therapy at a dose of >20 mg daily >7 days or has had changes to their steroid regimen within 28 days of screening.     

2.            Patient has 2016 WHO-defined transformation to leukemia.       

3.            Patient has AML M4 (French-American-British subtype; myelomonocytic). (NB if this is suspected, the NPM1 gene must be assessed to determine eligibility.)         

• Age 18- 90 years.
• Able to communicate and participate in their own care.

• Speak a language that we do not have in-person translator at the clinic.

• Have a diagnosis of metastatic non small cell lung cancer.
• Undergoing 1st, 2nd or 3rd line of treatment or are in maintenance therapy.
• Subjects will be limited to older than 18 years old at the time of diagnosis.

• Have advanced terminal cancer, severe depression, or other psychiatric disorder or a sleep disorder other than insomnia (sleep apnea, restless leg syndrome, sleep related disorder of breathing).
• Regular use of psychotropic medication other than hypnotics (e.g., antidepressants) per chart review.

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

Inclusion Criteria - Longhaulers Cohort:

Subject population: 100 men and women who have been diagnosed with Post-COVID syndrome.

• Ability to give informed consent or LAR.
• At least 18 years old.
• Ability of subject or LAR to read and speak the English language.
• Positive PCR or antibody test within 18 months of initial study visit.
• Patient of the Long-Hauler Syndrome clinic and differential diagnosis of Long-Hauler Syndrome.

• Any potential participant who refuses medical record review.
• Pregnant females.
• Incarcerated individuals.
• Inability to cooperate or any medical condition that, in the opinion of the investigator, interferes with the evaluation of the study objectives or increases the subject’s risk by participating in the study.
• Patient is unfit to participate at the discretion of the Principal Investigator.

Inclusion Criteria - Control Cohort:

Subject population: 50 men and women who have not had a known case of COVID or Longhauler’s syndrome.

• Ability to give informed consent or LAR.
• At least 18 years old.
• Ability of subject or LAR to read and speak the English language.

• Known case of COVID-19.
• Any potential participant who refuses medical record review.
• Pregnant females.
• Incarcerated individuals.
• Inability to cooperate or any medical condition that, in the opinion of the investigator, interferes with the evaluation of the study objectives or increases the subject’s risk by participating in the study.
• Patient is unfit to participate at the discretion of the Principal Investigator.

Inclusion Criteria - COVID-19 Control Cohort:

Subject population: 50 men and women who have had a known case of COVID, but not Longhauler’s syndrome.

• Ability to give informed consent or LAR.
• At least 18 years old.
• Ability of subject to read and speak the English language.
• Known case of COVID-19.

• Known Longhauler’s syndrome/Post-COVID
• Any potential participant who refuses medical record review.
• Pregnant females.
• Incarcerated individuals.
• Inability to cooperate or any medical condition that, in the opinion of the investigator, interferes with the evaluation of the study objectives or increases the subject’s risk by participating in the study.

Eligibility last updated 11/19/21. Questions regarding updates should be directed to the study team contact.

•  age >18
• Healthy control volunteers
• Patients with Multiple Sclerosis (Relapsing remitting multiple sclerosis and progressive multiple sclerosis)

Exclusion criteria:

Patients with anxiety or claustrophobia

• This study will include both a prospective component looking forward, and a retrospective component looking backward.
• Participants in the established clinical HABIT program will be invited to participate in this study, including patients diagnosed with Mild Cognitive Impairment and a partner. The partners are often spouses, but could be adult children, other family members, or friends.
• In addition, this study includes a retrospective arm, using information already collected under related IRB-approved studies.

• Any inclusion criteria that cannot be met.

• Participants undergoing corneal endothelial transplantation because of corneal endothelial dysfunction
• Any age (expected range will be 40-90 in FECD)
• Any sex or race

• Corneal disease other than FECD

• Patients must be considered suitable candidates for a penile prostheses as dictated by the surgeon.
• All stages of PP surgery will be included: primary implants, revision, salvage, infected.
• Patients with prior histories of penile prostheses will have data obtained about their prior devices where available. This information will include the number of devices, penile prostheses-related surgeries, and complications relating to these procedures.
• Each time a new device or new component is placed (revision, salvage) will result in a new data entry point.

• Male or female, ≥ 10 years of age.
• Diagnosis of Hidradenitis Suppurativa (HS) by a dermatologist or practitioner experienced in making a diagnosis of HS.
• Written informed consent (and assent when applicable) obtained from subject or subject’s legal representative and ability for subject to comply with the requirements of the study.
• Immediate family members (for saliva and genetics data).

• Inability to give informed consent or unavailability of a parent/guardian who is able and willing to give informed consent.

Inclusion Criteria;

• Pre-menopausal (21
  •50 years of age).
• Study group will consist of women seeking hysterectomy for possible adenomyosis adenomyomectomy.
• Controls will consist of women seeking hysterectomy for uterine prolapse or pelvic pain or transgender men prior to androgen treatment and whose pathology shows a uterus < 100 grams with no evidence of adenomyosis, endometriosis, or leiomyomas.

• No ua\se of GnRH analogues, aromatase inhimitors, selective E2 or P4 receptor modulators, oral contraceptives, or immunotherapy within 3 months prior to surgery in any patient.
• No history /confirmation or suspicion of autoimmune disease, fibromyalgia, endometriosis, or leiomyomas in any patient.
• No current or previous history of STDs, pelvic inflammatory disease, endometrial/cervical cancer in any patient.
• Women who do not exhibit menstrual cycles.

Eligibility last updated 10/21/21. Questions regarding updates should be directed to the study team contact.

• Treated with CARPEDIEM as part of standard of care at a participating institution.
• Within the United States.

• Parents/legally authorized representative unable or unwilling to provide consent.

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

Eligibility last updated 9/12/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria:

• Must be ≥ 18 years old.
• Individual undergoing elective ureteroscopy and laser lithotripsy for renal or ureteral stones.

• Under 18 years of age.
• Individual cannot be undergoing elective ureteroscopy and laser lithotripsy for renal or ureteral stones.

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

Eligibility last updated 3/20/23. Questions regarding updates should be directed to the study team contact.

• Patients diagnosed with or suspected to have a mitochondrial disorder
• Adult carriers of known mitochondrial DNA mutations
• Patients with laboratory analysis indicative of a mitochondrial disorder.
• Medical information and tissue samples are also accepted from deceased individuals who fulfill the above criteria.

• Patients not suspected of having a mitochondrial disorder
• Patients not suspected of carrying a mitochondrial DNA or nuclear DNA mutation that affects mitochondrial function.

• Children aged 14 days
  •17 years.
• At least moderate PARDS, bilateral lung disease, intubated within four days of severe PARDS and no exclusion criteria.

• Children will be excluded if they have any of the following at the start of mechanical ventilation: perinatal related lung disease, congenital diaphragmatic hernia or congenital/acquired diaphragm paralysis, respiratory failure explained by cardiac failure or fluid overload, cyanotic heart disease, cardiomyopathy, unilateral lung disease, primary pulmonary hypertension, status asthmaticus (patient with a severe asthma exacerbation. A previous history of asthma or the use of bronchodilators is NOT an exclusion if the primary disease process is not considered to be obstructive airway disease), obstructive airway disease (e.g., severe airways disease without parenchymal involvement or disease characterized by hypercapnia with FiO2 < 0.30 and/or evidence of increased resistance visible on the flow – time scalar and/or presence of intrinsic PEEP),  bronchiolitis obliterans, post Hematopoietic Stem Cell Transplant, post lung transplant, home ventilator (including noninvasive) dependent, neuromuscular respiratory failure, critical airway (e.g., post laryngotracheal surgery or new tracheostomy) or anatomical obstruction of the lower airway (e.g., mediastinal mass), facial surgery or trauma in previous 15 days, head trauma, intracranial bleeding, unstable spine, femur or pelvic fractures, acute abdominal process/open abdomen, supported on ECMO, previously enrolled in current study, family/medical team deciding not to provide full support, enrolled in any other critical care interventional clinical trial concurrently and known pregnancy.

Eligibility last updated 10/7/21. Questions regarding updates should be directed to the study team contact.

• Male or female, ≥ 18 year of age.
• Group 1: : Papilledema from idiopathic intracranial hypertension and others suspected of elevated intracranial pressure, including obstructive hydrocephalus, or suspected biomechanical changes to the eye, such as choroidal fold.
• Group 2: Patients without raised intracranial pressure.

• Age < 18.
• Pregnancy (self-reported).
• Individuals for whom MR is contraindicated.

Eligibility last updated 10/27/21. Questions regarding updates should be directed to the study team contact.

• Wait listed for liver transplantation with poor 6 MWT

• Age < 18 years
• Recent hospitalization (within 14 days) due to decompensation, variceal bleeding in the previous 1 month
• Large esophageal varices without primary prophylaxis
• Active excessive alcohol intake (in the previous 3 months)
• Current overt uncontrolled hepatic encephalopathy
• Hepatopulmonary syndrome with uncontrolled hypoxia
• Portopulmonary hypertension
• Inability to perform exercise
• Marked symptomatic comorbidities (cardiac, pulmonary, renal)

• Diagnosis of IPF or other progressive fibrotic interstitial lung disease, with a minimum of > 10% fibrosis on computed tomography imaging.
• Clinically meaningful breathlessness: modified Medical Research Council (mMRC) dyspnea score >1.

• Inability to walk (orthopedic/neurologic/cardiac limitation causing immobility).
• Cognitive impairment or inability to understand and follow instructions.
• Traditional PR completed within 3 months of study recruitment.
• Hospice or end-of-life care at the time of screening.
• Acute exacerbation at the time of screening.

Eligibility last updated 8/13/21. Questions regarding updates should be directed to the study team contact.

• Participants from an existing IRB approved protocol (#18-008476, #14-004401, #712-98)

• Unable to complete study activities.
• Unable to read and speak English.

• Patient must be ≥ 18 years and ≤ 39 years of age at registration.
• Patient must have a histologically confirmed diagnosis of primary cancer of any stage within 12 weeks (84 days) at registration.
• Patient must have received, be currently receiving or planning to receive treatment for cancer, including surgery and/or chemotherapy and/or radiation therapy.
• Patient must have an ECOG performance status 0-3.
• Patient must have a life expectancy > 24 months.
• Patient must be able to complete questionnaires in English.
• Patient must have internet access through computer, tablet, or smartphone.
• Patient must have an email address.
• Patient must have a mobile phone able with text messaging capabilities.
• Patient must be able to accurately provide self-report data (e.g., per clinical judgment, cognitive function is intact). Patient must be able to provide informed consent.

• Patient must not have a recurrence or second primary cancer.
• Patient must not have basal cell skin carcinoma.

Eligibility last updated 2/17/22. Questions regarding updates should be directed to the study team contact.

• Resident, fellow or teaching physicians participating and endoscopic sinus surgery for chronic rhinosinusitis.

• Anyone not meeting inclusion criteria or anyone not wishing to participate.