araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 63-year-old female with aortic aneurysm; genetic feature: ACTA2

Clinical trial: Biomarker Profiling in Abdominal Aortic Aneurysm Patients

Summary: The BIOMArCS-AAA study aims to investigate the associations of (temporal patterns of) blood biomarkers with aneurysm growth in patients with abdominal aortic aneurysm (AAA), with particular attention to biomarkers that have demonstrated prognostic value for adverse disease outcomes in coronary artery disease and biomarkers for the main genetic pathways associated with AAA.

Detailed description: BIOMArCS-AAA is an observational, multicenter study. Patients with an abdominal aortic aneurysm (AAA) will be recruited through the vascular surgery outpatient clinic of Erasmus MC and Maasstad Ziekenhuis, the Netherlands. The prospective, longitudinal part of the study will include an arm with 120 AAA watchful waiting patients and an arm with 120 AAA patients undergoing endovascular aneurysm repair (EVAR), both with a 24-month follow-up period. Clinical data collection, and blood sampling will be conducted at baseline, at 1 month after EVAR and at 6, 12, 18 and 24 months for all patients. CT will be conducted at baseline and 12 and 24 months, plus at 1 month in the EVAR patients. Quality of life and depression questionnaires will be performed at baseline, at 12 and 24 months of follow-up in all patients, and at 1 month only in EVAR patients. Additionally, a cross-sectional study will be performed in 200 patients treated for AAA with EVAR in the past years. In these patients, clinical data collection, blood sampling, ultrasound and CT will be performed at their next regular outpatient clinic visit.

Eligibility: Inclusion Criteria:
  -  Age of 18 years or older
  -  Capable of understanding and signing informed consent AND one of the following
  1. Diagnosis of AAA, with a diameter ≥40mm, based on any imaging technique and treated by watchful waiting strategy (Prospective longitudinal study, Arm 1 watchful waiting group)
  2. Planned to undergo EVAR for AAA (Prospective longitudinal study, Arm 2 EVAR group)
  3. Underwent EVAR for AAA in past years (Cross-sectional study)
  Exclusion Criteria:
  -  Patients with isolated iliac artery aneurysm, traumatic aneurysm, anastomotic aneurysm and infectious aneurysm
  -  Patients with a clinical diagnosed thoracic aneurysm (i.e. located in the chest, above the diaphragm)
  -  Coexistent condition with life expectancy ≤ 1 year
  -  Dialysis dependent, (end stage) renal disease patients
  -  Women of childbearing age
  -  Linguistic barrier
  -  Unlikely to appear at all scheduled follow-up visits

Relevance to patient case: not relevant
Patient case: 63-year-old female with aortic aneurysm; genetic feature: ACTA2

Clinical trial: Evaluation of the Effectiveness of Ischemic Pre-conditioning on the Morbidity and Mortality of Open Surgery of Thoracoabdominal Aortic Aneurysms.

Summary: Patients having a planned open surgery of thoracoabdominal aortic aneurysms and enrolled in the study will be randomized the day of the surgery in 2 groups:
  -  Arm 1 : Patients with aortic clamping with pre-conditioning
  -  Arm 2 : Patients with aortic clamping without pre-conditioning Patients will be then followed, during 60 days after surgery.


Eligibility: Inclusion Criteria:
  1. Patient > 18 and <85 years old
  2. Patient having a planned surgery for a thoracoabdominal aortic aneurysm by direct approach,
  3. Patient with aortic aneurysm requiring supra-visceral aortic clamping and visceral artery reconstruction,
  4. Aortic aneurysmal patient with or without distal femoral circulatory assistance,
  5. Patient with aortic aneurysm of atheromatous or dissecting etiology,
  6. Woman of childbearing potential with effective contraception (estrogen-progestin or intrauterine device or tubal ligation), postmenopausal woman (≥ 12 months of amenorrhea not induced by therapy)
  7. Patient who read and understood the newsletter and signed the consent form
  8. Patient affiliated with a social security scheme
  Exclusion Criteria:
  1. Patient with aortic aneurysms requiring supra-visceral aortic clamping but not requiring visceral artery reconstruction (supra-visceral aortic clamping for renal aortic juxtaposition aorta),
  2. Patient with thoraco abdominal aortic aneurysms requiring a circulatory arrest (aortic aneurysms affecting the descending thoracic aorta or the aortic arch)
  3. Patient requiring emergency aortic surgery
  4. Patient under treatment known as interfering with PCI (Nicorandil or oral antidiabetic agents),
  5. Pregnant or lactating woman (negative result of baseline blood test)
  6. Participation in another interventional study within 28 days before randomization or during this study
  7. Person deprived of liberty by an administrative or judicial decision or person subject to a legal measure for the protection of adults,
  8. Patient under the protection of justice, patient under guardianship or curatorship.

Relevance to patient case: not relevant
Patient case: 63-year-old female with aortic aneurysm; genetic feature: ACTA2

Clinical trial: Study to Evaluate Efficacy and Safety of JTT-251 in Participants With Pulmonary Arterial Hypertension

Summary: Study to evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-251 administered for 24 weeks in participants with pulmonary arterial hypertension (PAH)

Detailed description: This is a study to evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-251 administered for 24 weeks in participants with pulmonary arterial hypertension (PAH). Participants completing this study (RELIEF-PAH) will be eligible to enroll in an open-label extension study (RELIEF-PAH OLE) to evaluate the long-term efficacy, safety, tolerability and pharmacokinetics of JTT-251 in participants with PAH.

Eligibility: Inclusion Criteria:
  -  Diagnosis of PAH as classified by idiopathic, heritable, drug and toxin- induced, congenital heart disease or associated with connective tissue disease (i.e., WHO Group 1)
  -  Clinical diagnosis of PAH confirmed by RHC at any time prior to Visit 1
  -  WHO functional status of Class II-IV at Visit 1
  -  Two 6MWD test measurements between 100 and 450 meters with a relative difference of ≤15%. The baseline 6MWD test must be performed at Visit 2 before randomization.
  -  Have a qualifying RHC performed between Visit 1 and Visit 2
  -  On stable dose(s) of guideline-directed medical therapy for PAH (endothelin receptor antagonists, phosphodiesterase type-5 (PDE-5) inhibitors, soluble guanylate cyclase stimulators and prostacyclin pathway analogs) for at least 90 days prior to the qualifying RHC
  Exclusion Criteria:
  -  PAH associated with portal hypertension, human immunodeficiency virus (HIV), schistosomiasis or sickle cell disease as well as participants with pulmonary parenchymal disease or thromboembolic disease
  -  Known significant left heart disease including: left ventricular dysfunction (i.e., left ventricular ejection fraction <35%); hemodynamically compromising, symptomatic, or severe aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation
  -  Pulmonary hypertension belonging to WHO groups 2 to 5
  -  Moderate to severe obstructive lung disease defined as forced expiratory volume in 1 second (FEV1) <55% of predicted value
  -  Moderate to severe restrictive lung disease defined as total lung capacity (TLC) <60% of predicted value
  -  Acute decompensated heart failure or hospital admission for worsening PAH symptoms within 30 days prior to the qualifying RHC

Relevance to patient case: not relevant
Patient case: 63-year-old female with aortic aneurysm; genetic feature: ACTA2

Clinical trial: Anticoagulation for Aortic Bioprosthesis (ANTIPRO)

Summary: This study evaluates the clinical and hemodynamic outcome in patients after aortic valve replacement. Half of the patients will receive warfarin + aspirin and the other half will receive only aspirin. The investigators will focus mainly on early bioprosthesis degeneration.

Detailed description: Aortic bioprosthesis have the advantage that they do not require life-long anticoagulation. Current guidelines support the use of aspirin (AAS) 100 mg as a class I indication.
  Current evidence, mainly derived from transaortic valve implantation (TAVI) patients, have shown that aortic bioprosthesis suffer subclinical thrombosis which may explain the increase in gradient and bioprosthetic degeneration. Anticoagulation in this cases improve leaflet mobility and decrease in gradient. Evidence supporting early anticoagulation in patients with aortic bioprosthesis is not as strong as in the case of mitral bioprosthesis. Nonetheless, current American Heart Association/American College of Cardiology (AHA/ACC) guidelines recommend (IIa) the use of warfarin for at least 3 months after aortic valve replacement.
  The aim is to conduct a single blinded (echocardiographist) randomized control study in patients who receive an aortic bioprosthesis. Comparison will be performed between the use of warfarin + aspirin vs aspirin alone. Duration of anticoagulation will be for 3 months and patients follow-up for 1 year. Clinical and echocardiographic evaluation will be performed in every patients. Some patients will undergo Positron Emission Tomography (PET-Scan).

Eligibility: Inclusion Criteria:
  -  Patients with indication of aortic valve replacement with bioprosthesis
  Exclusion Criteria:
  -  Concomitant mitral valve replacement
  -  Previous atrial fibrillation
  -  Previous use oral anticoagulation
  -  Contraindication for the use of oral anticoagulation (high risk of bleeding, intolerance, allergy)
  -  Jehovah witness
  -  Platelet count below 90,000.
  -  Liver disease

Relevance to patient case: not relevant
Patient case: 63-year-old female with aortic aneurysm; genetic feature: ACTA2

Clinical trial: Induced Pluripotent Stem Cells for Niemann Pick Disease

Summary: Establishment of individualized human cellular disease models based on induced pluripotent stem cells that reflect the broad heterogeneous phenotypic spectrum of Niemann Pick disease

Detailed description: Niemann-Pick disease type C (NPC) is a lipid storage disease that can present in infants, children, or adults. Neonates can present with ascites and severe liver disease from infiltration of the liver and/or respiratory failure from infiltration of the lungs. Other infants, without liver or pulmonary disease, have hypotonia and developmental delay. The classic presentation occurs in mid-to-late childhood with the insidious onset of ataxia, vertical supranuclear gaze palsy, and dementia. Dystonia and seizures are common. Dysarthria and dysphagia eventually become disabling, making oral feeding impossible; death usually occurs in the late second or third decade from aspiration pneumonia. Adults are more likely to present with dementia or psychiatric symptoms. The diagnosis of NPC is confirmed by biochemical testing that demonstrates impaired cholesterol esterification and positive filipin staining in cultured fibroblasts. Biochemical testing for carrier status is unreliable. Most individuals with NPC have NPC1, caused by mutations in the NPC1 gene; fewer than 20 individuals have been diagnosed with NPC2, caused by mutations in the NPC2 gene. Molecular genetic testing of the NPC1 genes detects disease-causing mutations in approximately 94% of individuals with NPC. Such testing is available clinically.
  NPC is inherited in an autosomal recessive manner. The phenotype (i.e., age of onset and severity of symptoms) usually runs true in families. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible when the two disease-causing mutations have been identified in the family.
  Though NPC is a pan-ethnic disorder, the prevalence of this autosomal-recessive disorder is elevated in countries with a higher frequency of consanguinity.
  Therefore, the goal of the study to prepare a cell culture from patients affected with Niemann Pick disease in order to identify novel pathways and proteins involved in disease progression that allow for an earlier diagnosis (i.e. before symptom onset) and that are suitable targets for an individualized therapeutic approach able to address not only the hepatic form, but also the neurologic form of the disease, which is less responsive to the current therapeutic approaches.

Eligibility: Inclusion Criteria:
  -  Informed consent will be obtained from the patient or the parents before any study related procedures
  -  Patients of both genders older than 6 months and younger than 80 years
  -  The patient has a diagnosis of Niemann Pick disease
  Exclusion Criteria:
  -  No Informed consent from the patient or the parents before any study related procedures
  -  Patients of both genders younger than 6 months or older than 80 years
  -  No diagnosis of Niemann Pick disease

Relevance to patient case: not relevant
Patient case: 63-year-old female with aortic aneurysm; genetic feature: ACTA2

Clinical trial: The 3q25 rs2305619 Polymorphism Associates With Microvascular Obstruction in STEMI

Summary: The investigators enrolled 217 patients with acute STEMI undergoing primary PCI. The rs2305619 polymorphism was evaluated by real time PCR and plasma PTX3 concentration was assessed by human PTX3 ELISA kit.

Detailed description: The investigators enrolled 217 patients with acute STEMI undergoing primary PCI in a tertiary care academic cardiovascular center. The rs2305619 polymorphism was evaluated by real time PCR and plasma PTX3 concentration was assessed by human PTX3 ELISA kit. The primary outcome of the study was the incidence of coronary microvascular obstruction defined as thrombolysis in myocardial infarction (TIMI) grade <3 flow after primary PCI or TIMI grade 3 flow with myocardial blush grade 0 or 1. Patients were grouped based on the genotypic variants (AA, AG and GG). The primary outcome was compared among the three variants, as well as the PTX3 concentration and 30-day mortality.

Eligibility: Inclusion Criteria:
  -  Patients with acute STEMI with symptom onset <12 h and treated by primary PCI
  Exclusion Criteria:
  -  STEMI patients who received fibrinolytic therapy

Relevance to patient case: not relevant
Patient case: 63-year-old female with aortic aneurysm; genetic feature: ACTA2

Clinical trial: LCZ696 in Advanced LV Hypertrophy and HFpEF

Summary: Patients with advanced LVH and HFpEF will be randomly assigned in open-label fashion to receive LCZ696 titrated to 200 mg twice daily or enalapril titrated to 20 mg twice daily, and will be treated for 24 weeks.

Detailed description: Heart failure with preserved ejection fraction (HFpEF) has a signiﬁcant morbidity and mortality, and therapies that have proven effective in HF with reduced EF have not been shown to improve long-term prognosis in HFpEF. Inhibition of circulating neprilysin could augment deficient NP-receptor GC signaling and therefore be beneficial in HFpEF, as suggested by the decrease in NP following administration of valsartan/sacubitril in the phase 2 (PARAMOUNT study). Use of valsartan/sacubitril is currently being tested in the multicenter PARAGON-HF trial with HFpEF patients. The investigators suppose the best candidates for LCZ696 therapy will be patients with HFpEF and advanced concentric LV hypertrophy and obesity, i.e. having the lowest BNP bioavailability.

Eligibility: Inclusion Criteria:
  1. Moderate/severe hypertensive left ventricular (LV) hypertrophy (LVMi ≥109 g/m² in women and ≥132 g/m² in men);
  2. New York Heart Association (NYHA) class II-III heart failure;
  3. Left ventricular ejection fraction > 50%;
  4. Increased LV filling pressures assessed at rest or at peak exercise by echocardiography
  5. Body mass index (BMI) > 30 kg/m²
  6. Signed and data informed consent
  Exclusion Criteria:
  1. Age ≤ 18 years;
  2. Evidence of myocardial ischemia during stress echocardiography;
  3. Chronic atrial flutter or atrial fibrillation;
  4. Alternative cause of left ventricular hypertrophy and impaired diastolic function (hypertrophic/restictive cardiomyopathy, aortic stenosis, constrictive pericarditis and etc.);
  5. NYHA classification I or decompensated heart failure at screening;
  6. Systolic blood pressure < 110 mmHg or > 180 mmHg;
  7. Diastolic blood pressure < 40 mmHg or > 100 mmHg;
  8. Anemia (Hb < 100 g/l);
  9. Significant left sided structural valve disease;
  10. Secondary hypertension;
  11. Dyspnea due to non-cardiac causes such as pulmonary disease, anemia, severe obesity, primary valvular, or myocardial diseases;
  12. Myocardial infarction or myocardial revascularization within the last 3 months of screening;
  13. Stroke or TIA within the last 3 months of screening;
  14. Autoimmunic and oncological diseases;
  15. Impaired renal function, defined as eGFR < 30 ml/min/1.73 m²;
  16. Impaired liver function;
  17. Potassium concentration >5.2 mmol/L.

Relevance to patient case: not relevant
Patient case: 63-year-old female with aortic aneurysm; genetic feature: ACTA2

Clinical trial: Fibroblast Specific Inhibition of LOXL2 and TGFbeta1 Signaling in Patients With Pulmonary Fibrosis.

Summary: This is a two part study. In the first part, the pharmacokinetic profile of Epigallocatechin-3-gallate (EGCG) in normal human volunteers given a single oral dose will be determined to set the dose for the second part of the study. In the second part of this study, lung biopsy fragments and urine samples from patients with interstitial lung disease treated with EGCG will be evaluated in biochemical assays and compared to samples from untreated control patients.

Detailed description: This is an interventional study intended to test inhibition of a signaling pathway in vivo in patients with interstitial lung disease, but not intended to affect lung function or disease modifications. Doses of oral Epigallocatechin-3-gallate (EGCG) that achieve plasma levels known to be safe in human volunteers and likely to target fibroblast TGFbeta RI kinase will be established. Disposable fragments of biopsies will be evaluated in biochemical assays including pSmad3 and Snail 1 or assayed to determine lysyl oxidase-like 2 (LOXL2) protein and LOXL2 enzyme activity. Urine collected before and after EGCG exposure will be used to determine whether terminal collagen cross-link breakdown products, termed pyridinoline/deoxypyridinoline (PYD/DPD) are changed from baseline.

Eligibility: Inclusion Criteria:
  -  Part 1: healthy volunteers
  -  Part 2:
  -  study will consist of patients presenting to the UCSF interstitial lung disease (ILD) outpatient clinic with imaging indicative of lung fibrosis but of uncertain classification, and who are willing to take EGCG for a minimum of 2 weeks prior to surgery.
  Exclusion Criteria:
  -  co-morbidities affect hepatic function, such as HCV infection, cirrhosis, or
  -  using drugs with significant hepatic toxicities

Relevance to patient case: not relevant
Patient case: 63-year-old female with aortic aneurysm; genetic feature: ACTA2

Clinical trial: INST 1204: PIK3CA Mutations as Biomarkers for Metastasis in Colon Cancer

Summary: This proposal seeks to further understand the contribution of the PIK3CA mutations in colon cancer, by correlating the type of hotspot mutation with the development of metastases in stage II and stage Ill patients.
  In order to do this, DNA will be extracted from either frozen or paraffin embedded colon cancer tissues to sequence PIK3CA, KRAS and BRAF. Clinical outcome data will be gathered to include metastases and survival to correlate with PIK3CA, KRAS and BRAF mutational status. Patients with stage II and stage Ill colon cancers will be identified in the University of New Mexico Human Tissue Repository and the NIH PLCO prevention trial biorepository.
  Existing banked tissues of stage II and Ill colon cancers will be collected. There will be no direct contact with living individuals. Epidemiological factors such as age, race, gender and outcome data of metastases and survival will be collected.

Detailed description: This proposal aims to identify PIK3CA mutations as a biomarker for metastasis.
  In order to do this, DNA will be extracted from either frozen or paraffin embedded colon cancer tissues to sequence PIK3CA, KRAS and BRAF. Clinical outcome data will be gathered to include metastases and survival to correlate with PIK3CA, KRAS and BRAF mutational status. Patients with stage II and stage Ill colon cancers will be identified in the University of New Mexico Human Tissue Repository and the NIH PLCO prevention trial biorepository.
  Existing banked tissues of stage II and Ill colon cancers will be collected. There will be no direct contact with living individuals. Epidemiological factors such as age, race, gender and outcome data of metastases and survival will be collected.
  Specific Aims:
  1. To develop and standardize methods for high throughput DNA extraction and analysis from colon tumors of patients with stage II and stage III disease harboring PIK3CA exon 9 and exon 20 mutations.
  2. To determine the correlation between wild type and PIK3CA, PIK3CA exon 9 and PIK3CA exon 20 mutations and development of metastatic disease and overall survival in stage II and stage III patients with colorectal cancer.

Eligibility: Inclusion Criteria:
  -  Specimen from patients with stage II and stage III colon cancer.
  Exclusion Criteria:
  -  Any other stage or type of disease outside of stage II and stage III colon cancer.

Relevance to patient case: not relevant
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: Effects of Meditation on Mechanism of Coronary Heart Disease

Summary: To study the effects of Transcendental Meditation on Coronary Heart Disease

Detailed description: Recent advances in our understanding of the pathophysiology of acute cardiac events - specifically, identification of the roles that arterial vasomotor dysfunction and autonomic nervous system imbalances play in the pathophysiologic cascade during such acute events - provides a platform for new mechanistic investigation of the interplay of psychosomatic stress and CHD (coronary heart disease). Preliminary evidence further suggests that Complementary and Alternative Medicine (CAM) practices, such as the Transcendental Meditation (TM) technique, can not only reduce stress but also reduce acute cardiac events in patients with CHD. Based on these and related data, we propose a randomized, blinded, controlled study of the effects of one CAM practice, the TM technique, compared to a control group, on the primary outcomes of (1) arterial vasomotor dysfunction (brachial artery reactivity); (2) autonomic nervous system imbalances (heart rate variability); (3) transient myocardial ischemia (ST-segment depression); and (4) the secondary outcomes of psychological stress and quality of life (anger, hostility, anxiety, depression, perceived health, disease-specific symptoms, and life stress/social resources).

Eligibility: Inclusion Criteria:
  -  Able to attend training sessions and meetings
  -  Local residence
  Exclusion Criteria:
  -  Comorbid disease precluding survival in group
  -  MI, unstable angina, CABG or PTCA within last three months.
  -  Cognitive/psychological/substance abuse impairment
  -  Atrial fibrillation, predominant pacemaker rhythm or significant conduction system disease
  -  Significant valvular heart disease
  -  Class III or IV heart failure
  -  Renal failure
  -  Participating in a formal stress management program
  -  Participation in another trial

Relevance to patient case: not relevant