• Presence of an external traumatic event that results in a spinal cord injury, including surgical procedures, radiation, and medical complications.
• Temporary or permanent loss of sensory and/or motor function as a result of the traumatic event.
•  Admission to the system within one year of injury.
• Discharge from the System Rehab as:
  • Having completed inpatient acute rehabilitation;
  • Deceased.
• Signed informed consent and HIPAA authorization forms.
• Reside in the geographic catchment area of the system at the time of the injury.  Patients may be injured outside of the catchment area.
• A US citizen or non-US citizen who is expected to stay in the catchment area.

• Must not have previously been treated at another model system for the injury.
  • Ensures that patients are enrolled into the database by only one model system.
• Must not have completed an organized rehabilitation program prior to the admission to the system.

Eligibility last updated 1/24/22. Questions regarding updates should be directed to the study team contact.

• Males and females, ≥ 12 years of age.
• Diagnosed with non-histaminergic normal C1-INH angioedema at the time of enrollment into the antecedent Study SHP643-303.  
• Participants must have completed the treatment period (through Visit 26/Day 182) of Study SHP643-303 without reporting a clinically significant TEAE that would preclude subsequent exposure to lanadelumab.
• Agree to adhere to the protocol-defined schedule of treatments, assessments, and  procedures.
• Males, or non-pregnant, non-lactating females who are of child-bearing potential and who agree to be abstinent or agree to comply with the applicable contraceptive requirements of this protocol for the duration of the study; or females of  non-childbearing potential, defined as surgically sterile (status post hysterectomy,  bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least  12 months.  
• The participant (or the participant's parent/legal guardian, if applicable) has provided written informed consent approved by the institutional review board/research  ethics board/ethics committee (IRB/REB/EC) at any time prior to study start.
• If the  participant is a minor (i.e., less than 18 years of age), have a parent/legal guardian who is informed of the nature of the study provide written informed consent (i.e., permission) for the minor to participate in the study before any study-specific  procedures are performed.
• Assent will be obtained from minor participants.  

• Discontinued from Study SHP643-303 after enrollment but before Visit 26  for any reason.
• Presence of important safety concerns identified in Study SHP643-303 that would preclude participation in this study.  
• Dosing with an investigational product (IP, not including IP defined in antecedent  Study SHP643-303 or exposure to an investigational device within 4 weeks prior to Day 0.
• Participant has a known hypersensitivity to the investigational product or its  components.
• Have any condition (surgical or medical) that, in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude the successful conduct of  the study, or interfere with interpretation of the results (e.g., significant  pre-existing illness or other major comorbidities that the investigator considers may confound the interpretation of study results).

• Patients 18 and older, inclusive; AND
• Patients who meet the 2013 ACR/EULAR classification criteria for systemic sclerosis; AND
• < 5 years from onset of first non-RP symptom attributed to systemic sclerosis.

• Patients under 18 years of age.
• Patients with cognitive impairment that will interfere with conducting the study. Study staff should determine if the patient, at that moment, has the cognitive capacity to understand what the study entails, assent to participate, and complete the assessments. If there is question as to whether a patient may meet this criterion, RCs/RAs should defer to the site PI trained on the study to help determine; OR
• Patients who are non-English Speaking. The patient must be able to proficiently read, speak, and understand English in order to be eligible.

• Parent or LAR has signed information consent.
• Subject weighs between 2.5-10 kg (or 5.5-22 lbs).
• Subject is receiving medical care in an intensive care unit.
• Parental or LAR consent to receive full supportive care through aggressive management utilizing all available therapies for a minimum of 96 hours.
• Subject has a clinical diagnosis of acute kidney injury per Kidney Disease Improving Global Outcomes (KDIGO) criteria or fluid overload requiring CRRT.

• Subject is not expected to survive 72 hours due to an irreversible medical condition, in the opinion of the investigator.
• Subject has irreversible brain damage, in the opinion of the investigator.
• Subject is intolerant to anticoagulation, as documented in the medical record.
• Subject has a Do Not Attempt Resuscitate (DNAR), Allow Natural Death (AND), withdrawal of care or similar order, or anticipated change in status, in the opinion of the investigator, within the next 7 days.
• Subject has pre-existing end-stage renal disease or pre-existing, advanced chronic kidney disease, defined as an estimated Glomerular Filtration Rate (eGRF) < 30 ml/min/1.73m^2.
• Subject has received at least 12 hours of CRRT with another machine (not including ECMO) during the current hospitalization.
• Subject is currently or has chronically been treated with a circulatory support device (i.e., left ventricular assist device (LVAD)) other than ECMO.
• Subject has had prior CRRT treatments using the Carpediem™ system.
• Subject is enrolled in clinical trials or being treated with other investigational therapeutic devices or products for acute kidney injury or fluid overload.
• Subject has any other medical condition that may confound the study objectives, in the opinion of the investigator.

Eligibility last updated 12/9/21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 1/25/23. Questions regarding updates should be directed to the study team contact.

ts who tend to hyperhidrosis in the back area

Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this
study:
1. At the time of randomization, requires supplemental oxygen ≥2 LPM due to hypoxemia.
Hypoxemia can be defined by meeting at least one of the following criteria:
 
•SpO2 <92% on or off supplemental oxygen
  - Respiratory failure necessitating mechanical or non-invasive ventilation (CPAP or Bi-PAP)
  - Written declaration from Investigator that subject is clinically hypoxemic and removal of oxygen supplementation would not be considered clinically appropriate for the purpose of measuring SpO2 while on room air
   Note: Documentation of hypoxemia prior to or during the most recent oxygen supplementation must be available in source.
   Note: Subjects who also require invasive mechanical ventilation (MV) or non-invasive positive pressure ventilation (CPAP or bi-PAP) are eligible, although ventilator support is not mandatory
2. Immunocompromised, as defined by one or more of the following:
  - Received an autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at any time in the past
 
•Received a solid organ transplant at any time in the past
  - Has been or is currently being treated with chemotherapy for hematologic malignancies (e.g., leukemia, myeloma, lymphoma) and/or solid tumor malignancies (e.g., lung, breast, brain cancer) at any time in the past
 
•Has an immunodeficiency due to congenital abnormality (only applicable to subjects age < 18 years old) or pre-term birth (only applicable to subjects age ≤ 2 years old)
3. Has, within 3 days prior to randomization, a confirmed LRTI with a sialic acid dependent respiratory virus (SAD-RV, see definition). This can be confirmed by:
 
•bronchoalveolar lavage (BAL) positive for SAD-RV
 
•lung biopsy positive for SAD-RV
 
•chest imaging with a new or worsening finding of pulmonary infiltrate, bronchiolitis, or pneumonitis temporally associated with an upper respiratory tract sample (e.g., tracheal aspirate, sputum, nasopharyngeal swab (NPS), nasopharyngeal wash) positive for SADRV
   Note: These requirements can be fulfilled by results from samples and/or chest imaging that are collected/performed locally as per standard of care within 3 days prior to randomization.
   Note: For all subjects, after obtaining informed consent but within 3 days prior to randomization, a separate nasopharyngeal swab sample will be collected and sent to thecentral laboratory for confirmation of a SAD-RV. The results from the central lab analysis are not required to initiate the subject on study treatment.
4. If female, subject must meet one of the following conditions:
 
•Not be of childbearing potential, defined as one or more of the following conditions:
     - Premenarchal
     - Postmenopausal for at least 1 year
     - Surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy;
 
•Be of childbearing potential and meet all of the following criteria:
     - Has a negative urine or serum pregnancy test (beta-human chorionic gonadotropin) at screening
     - Agrees to practice an acceptable method of contraception (or meets criteria for waiving contraception) from screening until at least 30 days after last dose of study medication (see Section 8.10.1 for details)
Additional contraception requirements may need to be followed according to local regulations and/or requirements.
5. Non-vasectomized males are required to practice effective birth control methods (see Section 8.10.1) from screening until at least 30 days after last dose of study medication
6. Capable of understanding and complying with procedures as outlined in the protocol as judged by the Investigator and able to sign informed consent form prior to the initiation of any screening or study-specific procedures. Subjects must have the ability to return to the hospital to comply with required procedures if they are discharged during the study.
   Note: For subjects, including minors and patients with medical incapacity or impaired consciousness such that they are not able to give fully informed voluntary consent, the subjects' legal representative (parent, guardian or surrogate) must sign an institutional review board (IRB)/independent ethical committee (IEC)-approved informed consent document prior to the initiation of any screening or study-specific procedures. Minor subjects must also sign an IRB/IEC-approved assent form unless not required per local and institution regulations
 

 Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
1. Subjects may not be on hospice care or, in the opinion of the investigator, have a low chance of survival during the first 10 days of treatment
2. Subjects with Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or Alkaline Phosphatase (ALP) ≥3x ULN and Total Bilirubin (TBILI) ≥2x ULN
Note: Subjects with ALT/AST/ALP ≥ 3x ULN AND TB ≥2x ULN that have been chronically stable (for >1 year on more than one assessments) due to known liver pathology including malignancy (primary or metastasis), chronic medications, transplantation, or chronic infection will not be excluded
3. Female subjects breastfeeding or planning to breastfeed at any time through 30 days after the last dose of study drug
4. Subjects taking any other investigational drug used to treat pulmonary infection.
5. Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect subject safety and/or compliance
6. Subjects with known hypersensitivity to DAS181 and/or any of its components

7. Subjects with severe sepsis due to either their baseline SAD-RV infection or a concurrent viral, bacterial, or fungal infection and meet at least one of the following criteria:
   - Has evidence of vital organ failure outside of the lung (e.g., liver, kidney)
   - Requires vasopressors to maintain blood pressure

Inclusion Criteria

Subjects must meet the following inclusion criteria to qualify for the study:

• Willing and able to provide written informed consent. If the subject is unable to consent for himself/herself, a legally authorized representative must provide informed consent on his/her behalf.
• Males or females ≥18 years of age.
• Have received solid organ transplant or allogeneic hematopoietic stem cell transplant at any time or have another immunocompromising condition.

Exclusion Criteria

Subjects must NOT meet any of the following exclusion criteria to qualify for the study:

• Severe neutropenia (absolute neutrophil count <500 cells/microL).
• Profound lymphopenia (<300 cells/microL).
• The Principal Investigator (PI) is of the opinion the subject should not participate in the study.
• Females who are pregnant.

Eligibility last updated 11/3/22. Questions regarding updates should be directed to the study team contact.

• Adults, 18-75 years of age.
• Children 3 to < 18 years of age.
• Able to read or understand English or Spanish.
• Able to provide a healthcare provider or clinician to receive results.
• Willing to accept GIRA report.

• Inability to provide consent.
• Transplant (solid organ or bone marrow) or transfusion within 8 weeks.
• Research staff and investigators in eMERGE.
• Unable to provide a HCP to receive results.
• Not a patient at parent institution.

• Patients must understand and provide written informed consent prior to initiation of any study-specific procedures.
• ≥ 18 years of age.
• Patients must have a diagnosis of confirmed malignancy.
• Patient is a good medical candidate for a standard of care or research biopsy or surgical procedure to obtain tissue or has tissue available for analysis that has been collected within 12 months of signing consent.

• Uncontrolled concurrent illness including psychiatric illness, or situations that would limit compliance with the study requirements or the ability to willingly give written informed consent.
• Inaccessible tumor for biopsy or patient does not have tumor tissue available for research use.
• Biopsy must not be considered to be more than minimal risk to the patient.
• Contraindications to percutaneous biopsy:
  • Significant coagulopathy that cannot be adequately corrected;
  • Severely compromised cardiopulmonary function or hemodynamic instability;
  • Lack of a safe pathway to the lesion;
  • Inability of the patient to cooperate with, or to be positioned for, the procedure.

Eligibility last updated 11/10/21. Questions regarding updates should be directed to the study team contact.

• Adult (18 years or older).
• Able to provide informed consent 
• Able to provide samples in English.
• U.S. based patient.

• Age < 18 years of age.
• Unable to provide samples in English (i.e., need for interpreter flag in Epic).
• Nonverbal / No speech.
• HPP (High Profile Patient) status.
• International patient.

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

• Patient must be ≥ 2.5 years of age.
• Patient and/or authorized representative must be willing and able to give informed consent/assent and any authorizations required by local law for participation in the study.
• Patient and their caregiver must be willing and able (in the Investigator’s opinion) to comply with all protocol requirements.
• Patient must have completed dosing with STK-001 and the End of Study Visit in Study STK-001-DS-101, with an acceptable safety profile per Investigator judgment.
• Patient must have satisfactory compliance with study visits and procedures in Study STK-001-DS-101 per Investigator and Sponsor judgment.
• Patient must meet age-appropriate institutional standard practices for intrathecal (IT) drug administration procedures.
• Patient and/or family (or caretaker) must be sufficiently fluent in English or Spanish to be able to complete questionnaires relevant to this study.
• Patient must have completed Study STK-001-DS-101 within 4 weeks of the start of their participation in Study STK-001-DS-501, unless approved by the Sponsor.

• Patient has met any withdrawal criteria from Study STK-001-DS-101.
• Patient is currently being treated as maintenance therapy with an antiepileptic drug acting primarily as a sodium channel blocker including phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide.
• Patient has clinically significant unstable medical conditions other than epilepsy.
• Patient has had clinically relevant symptoms or a clinically significant illness (in the judgment of the Investigator) at Screening or prior to dosing on Day 1, other than epilepsy.
• Patient has a spinal deformity or other condition that may alter the free flow of CSF or has an implanted CSF drainage shunt.
• Patient has clinically significant (in the judgment of the Investigator) abnormal laboratory values at baseline or prior to dosing on Day 1.
• Patient has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3-fold upper limit of normal (ULN), serum creatinine > ULN or platelet count < lower limit of normal at baseline and upon repeat testing.
• Patient has clinically significant abnormalities (in the judgment of the Investigator) in the 12-lead ECG measured at Screening/Baseline (This includes 12-lead ECG from STK-001-DS-101 [Visit 6 or Visit 9], if STK-001-DS-101 Visit 6 or Visit 9 and STK-001-DS-501 Visit 1 are the Same Day).
• Patient has a psychiatric or behavioral disorder which, in the opinion of the Investigator, may interfere with the patient’s participation in the study.
• Patient is currently taking, or within 4 weeks prior to Screening/Baseline has taken any anticoagulant (including but not limited to heparins, warfarin and other vitamin K antagonists, dabigatran, rivaroxaban and apixaban), or within 7 days prior to Screening/Baseline, has taken any antiplatelet (including but not limited to aspirin, non-steroidal anti-inflammatory drugs, clopidogrel, ticlopidine. and dipyridamole).
• Patient is a female of childbearing potential, or patient is a fertile male with female partner(s) of childbearing potential, unless willing to ensure that they or their partners use effective contraception throughout the duration of the study and for at least 6 months after their last dose of STK-001.
• . Patient is a female who is lactating or planning pregnancy during the duration of the study and for at least 6 months after their last dose of STK-001.
• Patient has any other significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, may influence the results of the study, or may affect the patient’s ability to participate in the study.
• Patient has been treated (or is being treated) with an investigational product (other than STK-001) since participating in Study STK-001-DS-101.
• Patient is participating in an observational study, unless approved by the Sponsor.

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

Eligibility last updated 4/25/23. Questions regarding updates should be directed to the study team contact.

• Patients referred to the Mayo Clinic cardio-oncology clinic.
• Adults ≥ 18 years old.

• Individuals < 18 years old.

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

Eligibility last updated 10/18/22. Questions regarding updates should be directed to the study team contact.

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
• The patient must have an ECOG performance status of 0 or 1.
• The patient must have undergone a lumpectomy and the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. (Patients with margins positive for LCIS are eligible without additional resection).
• The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
• Patient must have undergone axillary staging (sentinel node biopsy and/or axillary node dissection).
• The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
  • By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm);
  • By pathologic evaluation, ipsilateral nodes must be pN0. (Patients with pathologic staging of pN0(i+) or pN0(mol+) are NOT eligible);
  • Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core biopsy or resected specimen;
    • ** For patients with a T1a tumor (less than or equal to 0.5 cm in size) who do not already have an Oncotype DX Recurrence Score at study entry, a specimen (unstained blocks or slides) must be sent to the Genomic Health centralized laboratory.
  • The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with greater than or equal to 1% ER or PgR staining by IHC are considered positive;
  • The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines.
• Patients may be premenopausal or postmenopausal at the time of study entry. For study purposes, postmenopausal is defined as: age 56 or older with no spontaneous menses for at least 12 months prior to study entry; or a documented hysterectomy; or age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) and with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standard; or documented bilateral oophorectomy.
• The interval between the last surgery for breast cancer (including re-excision of margins) and study entry must be no more than 70 days.
• The patient must have recovered from surgery with the incision completely healed and no signs of infection.
• Bilateral mammogram or MRI within 6 months prior to study entry. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Patients must be intending to take endocrine therapy for a minimum 5 years duration (tamoxifen or aromatase inhibitor). The specific regimen of endocrine therapy is at the treating physician's discretion.

• Definitive clinical or radiologic evidence of metastatic disease. -pT2
  •pT4 tumors including inflammatory breast cancer.
• Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease.
• Patient had a mastectomy.
• Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
• Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by 4 or more centimeters. (Patients with multifocal carcinoma are eligible).
• Paget's disease of the nipple.
• Any history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated or not treated. (Patients with synchronous or previous ipsilateral LCIS are eligible).
• Synchronous or previous contralateral invasive breast cancer or DCIS. (Patients with synchronous and/or previous contralateral LCIS are eligible).
• Surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re- excision, the patient is eligible).
• Treatment plan that includes regional nodal irradiation.
• Any treatment with radiation therapy, chemotherapy, biotherapy, and/or endocrine therapy administered for the currently diagnosed breast cancer prior to study entry. (Short course endocrine therapy of less than 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18).
• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry.
• Current therapy with any endocrine therapy such as raloxifene (Evista®), tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or breast cancer prevention. (Short course endocrine therapy of < 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18).
• Patients intending to continue on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible.
• Patients that discontinue oral, transdermal, or subdermal estrogen replacement prior to registration are eligible.
• Prior breast or thoracic RT for any condition.
• Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.
• Pregnancy or lactation at the time of study entry or intention to become pregnant during treatment.
  • Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to study entry.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of study therapy or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
• Use of any investigational product within 30 days prior to study entry.

Eligibility last updated 9/20/21. Questions regarding updates should be directed to the study team contact.

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
• The patient must have an ECOG performance status of 0 or 1.
• The patient must have undergone a lumpectomy and the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. (Patients with margins positive for LCIS are eligible without additional resection).
• The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
• Patient must have undergone axillary staging (sentinel node biopsy and/or axillary node dissection).
• The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
  • By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm);
  • By pathologic evaluation, ipsilateral nodes must be pN0. (Patients with pathologic staging of pN0(i+) or pN0(mol+) are NOT eligible);
  • Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core biopsy or resected specimen;
    • ** For patients with a T1a tumor (less than or equal to 0.5 cm in size) who do not already have an Oncotype DX Recurrence Score at study entry, a specimen (unstained blocks or slides) must be sent to the Genomic Health centralized laboratory.
  • The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with greater than or equal to 1% ER or PgR staining by IHC are considered positive;
  • The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines.
• Patients may be premenopausal or postmenopausal at the time of study entry. For study purposes, postmenopausal is defined as: age 56 or older with no spontaneous menses for at least 12 months prior to study entry; or a documented hysterectomy; or age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) and with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standard; or documented bilateral oophorectomy.
• The interval between the last surgery for breast cancer (including re-excision of margins) and study entry must be no more than 70 days.
• The patient must have recovered from surgery with the incision completely healed and no signs of infection.
• Bilateral mammogram or MRI within 6 months prior to study entry. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Patients must be intending to take endocrine therapy for a minimum 5 years duration (tamoxifen or aromatase inhibitor). The specific regimen of endocrine therapy is at the treating physician's discretion.

• Definitive clinical or radiologic evidence of metastatic disease. -pT2
  •pT4 tumors including inflammatory breast cancer.
• Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease.
• Patient had a mastectomy.
• Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
• Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by 4 or more centimeters. (Patients with multifocal carcinoma are eligible).
• Paget's disease of the nipple.
• Any history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated or not treated. (Patients with synchronous or previous ipsilateral LCIS are eligible).
• Synchronous or previous contralateral invasive breast cancer or DCIS. (Patients with synchronous and/or previous contralateral LCIS are eligible).
• Surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re- excision, the patient is eligible).
• Treatment plan that includes regional nodal irradiation.
• Any treatment with radiation therapy, chemotherapy, biotherapy, and/or endocrine therapy administered for the currently diagnosed breast cancer prior to study entry. (Short course endocrine therapy of less than 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18).
• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry.
• Current therapy with any endocrine therapy such as raloxifene (Evista®), tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or breast cancer prevention. (Short course endocrine therapy of < 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18).
• Patients intending to continue on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible.
• Patients that discontinue oral, transdermal, or subdermal estrogen replacement prior to registration are eligible.
• Prior breast or thoracic RT for any condition.
• Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.
• Pregnancy or lactation at the time of study entry or intention to become pregnant during treatment.
  • Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to study entry.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of study therapy or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
• Use of any investigational product within 30 days prior to study entry.

Eligibility last updated 9/20/21. Questions regarding updates should be directed to the study team contact.

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
• The patient must have an ECOG performance status of 0 or 1.
• The patient must have undergone a lumpectomy and the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. (Patients with margins positive for LCIS are eligible without additional resection).
• The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
• Patient must have undergone axillary staging (sentinel node biopsy and/or axillary node dissection).
• The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
  • By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm);
  • By pathologic evaluation, ipsilateral nodes must be pN0. (Patients with pathologic staging of pN0(i+) or pN0(mol+) are NOT eligible);
  • Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core biopsy or resected specimen;
    • ** For patients with a T1a tumor (less than or equal to 0.5 cm in size) who do not already have an Oncotype DX Recurrence Score at study entry, a specimen (unstained blocks or slides) must be sent to the Genomic Health centralized laboratory.
  • The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with greater than or equal to 1% ER or PgR staining by IHC are considered positive;
  • The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines.
• Patients may be premenopausal or postmenopausal at the time of study entry. For study purposes, postmenopausal is defined as: age 56 or older with no spontaneous menses for at least 12 months prior to study entry; or a documented hysterectomy; or age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) and with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standard; or documented bilateral oophorectomy.
• The interval between the last surgery for breast cancer (including re-excision of margins) and study entry must be no more than 70 days.
• The patient must have recovered from surgery with the incision completely healed and no signs of infection.
• Bilateral mammogram or MRI within 6 months prior to study entry. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Patients must be intending to take endocrine therapy for a minimum 5 years duration (tamoxifen or aromatase inhibitor). The specific regimen of endocrine therapy is at the treating physician's discretion.

• Definitive clinical or radiologic evidence of metastatic disease. -pT2
  •pT4 tumors including inflammatory breast cancer.
• Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease.
• Patient had a mastectomy.
• Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
• Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by 4 or more centimeters. (Patients with multifocal carcinoma are eligible).
• Paget's disease of the nipple.
• Any history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated or not treated. (Patients with synchronous or previous ipsilateral LCIS are eligible).
• Synchronous or previous contralateral invasive breast cancer or DCIS. (Patients with synchronous and/or previous contralateral LCIS are eligible).
• Surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re- excision, the patient is eligible).
• Treatment plan that includes regional nodal irradiation.
• Any treatment with radiation therapy, chemotherapy, biotherapy, and/or endocrine therapy administered for the currently diagnosed breast cancer prior to study entry. (Short course endocrine therapy of less than 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18).
• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry.
• Current therapy with any endocrine therapy such as raloxifene (Evista®), tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or breast cancer prevention. (Short course endocrine therapy of < 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18).
• Patients intending to continue on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible.
• Patients that discontinue oral, transdermal, or subdermal estrogen replacement prior to registration are eligible.
• Prior breast or thoracic RT for any condition.
• Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.
• Pregnancy or lactation at the time of study entry or intention to become pregnant during treatment.
  • Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to study entry.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of study therapy or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
• Use of any investigational product within 30 days prior to study entry.

Eligibility last updated 9/20/21. Questions regarding updates should be directed to the study team contact.

• Southeast Minnesota (SEMN, covering MCR and MCHS vicinities), Southwest Wisconsin (SWWI, covering MCR and MCHS vicinities), Florida (covering Jacksonville FL region) and Arizona (covering Scottsdale AZ region) residents (residency established at least one year prior to consent).
• Aged 18- 64 years at the time of consenting.
• Those who have primary care physician at Mayo Clinic and had at least one visit to one of Mayo Clinic sites within 3 years prior to the study index date.
• Those who authorize use of their medical record for research (MN only).
• Those who provide written consent to participate in the study.

• Subjects without authorization for use of medical records for research.
• Those who do not reside in catchment areas served by MCR/MCHS, MCF, and MCA.
• Those who receive primary care at a non-Mayo medical facility.
• Those who develop ARI after October 1st, 2022, if consent is done between October 1st, 2022, and November 30th, 2022.
• Those who refuse swab test.
• Those who cannot ambulate or those who are bedridden.
• Those with known cognitive impairment.
• Those who reside out of their resident counties > 2 weeks during winter season (Oct-April) and/or >4 weeks during summer season (May-Sep).

Both of the following criteria must be met for inclusion in this study OR Family members who are clinically unaffected or affected with the same suspected disorder as a patient with VUS:

• Clinically suspected diagnosis of a genetic disorder.
• All genetic testing performed to date has been equivocal.
• Examples of “equivocal” results include:
  • A variant or variants of uncertain significance identified in a gene or genes of interest; borderline hypo- or hypermethylation on a previous targeted methylation assay such as methylation-sensitive MLPA; borderline droplet count or copy number detected by ddPCR or qPCR, respectively;
  • A single mutation identified in a gene of interest, such as via Sanger sequencing, next generation sequencing, or chromosomal microarray, associated with an autosomal recessive disorder in which two mutations must be present in order to be causative (i.e., no second mutation was identified); a pathogenic or likely pathogenic finding that is inconsistent with the current clinical phenotype of the patient  (i.e., the patient’s presentation is still unsolved) or inconsistent with the currently known mode of inheritance for a particular genetic disorder.

• Blood transfusion within the past 2 weeks.
• Previous bone marrow transplant.
• Chemotherapy or radiation therapy within the past 6 months.

Eligibility last updated 3/7/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria;

• Individuals ≥ 18 years old.
• Documentation by a doctor of allergic reactions upon cannabis exposure.

• Individuals < 18 years old.
• Currently undergoing anti-IgE drug treatment (e.g., Omalizumab).

Eligibility last updated 12/3/21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 4/18/23. Questions regarding updates should be directed to the study team contact.

• Patients who receive a Hepatic Artery Infusion Pump at Mayo Clinic Rochester for localized unresectable liver metastases from colorectal cancer.
• Age ≥ 18 years old.
• Written consent.

• Age < 18 years old.
• Absence of written consent.
• Systemic disease.
• Pregnancy.

• Adult postmenopausal women, aged 45-60 years.
• Menopause symptoms (hot flashes/night sweats) rated moderate or greater or total MRS score ≥ 14.

• Current use of hormone therapy.

Eligibility last updated 3/10/22. Questions regarding updates should be directed to the study team contact.