araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Advanced Refractory Solid Tumors With TP53 Mutations Register Study

Summary: The efficacy and safety of the PARP inhibitor in combination with the VEGFR inhibitor will be investigated in advanced refractory solid tumors patients with TP53 mutation .

Detailed description: TP53 is a well-known tumor suppressor gene. Multiple studies have demonstrated that TP53 mutations are poor prognostic factor in advanced solid tumor, the TP53 gene is frequently inactivated by mutation in a majority of human tumors. However, no effective TP53 -based therapy has been successfully translated into clinical cancer treatment. So, investigators intend to review and evaluate the efficacy and safety of the PARP inhibitor in combination with the VEGFR inhibitor for TP53 mutation in advanced refractory solid tumors patients from a real-world population.

Eligibility: Inclusion Criteria:
  1. Is equal to or greater than 18 years of age.
  2. Histologic or cytologic confirmation of advanced refractory solid tumors with no standard treatment options, including some patients with advanced disease in reduced general condition (Eastern Cooperative Oncology Group (ECOG) 3 and 4).
  3. Patients with measurable or evaluable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
  4. Patients must be able to provide blood samples or tissue samples for NGS (Next Generation Sequencing) testing for understanding the TP53 gene status. The amount of blood and tissue samples should be able to meet the requirements of DNA extraction and quality control.
  5. Adequate baseline organ system function.
  6. Patients could receive treatment program from MTB (Molecular Tumor Board).
  7. No prior treatment with PARP combined with VEGFR inhibitions.
  8. Ability to understand and the willingness to provide a written informed consent document.
  Exclusion Criteria:
  1. Women who are pregnant or breastfeeding.
  2. Prior anti-cancer therapy or radiation therapy within 2 weeks prior to enrolment. Palliative radiotherapy to metastatic lesion(s) permitted providing that it has been completed at least 2 days prior to enrolment and no significant toxicity are expected.
  3. Clinically significant (active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months prior to study enrollment; unstable angina, congestive heart failure or a serious cardiac arrhythmia requiring medication.
  4. Active infection requiring systemic therapy.
  5. Patients unable to swallow orally administered medication.
  6. Prior treatment with PARP or VEGFR inhibitions.
  7. According to the investigator'judgment, there are serious, uncontrollable risks to patients'safety, or associated diseases (such as severe diabetes, thyroid disease, infection, spinal cord compression, superior vena cava syndrome, neurological or psychiatric disorders and so on) that affect the patients completion of the study.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Effect of Thyroid Hormone on Post-Myocardial Infarction Remodeling and Prognosis in STEMI Patients

Summary: This study aims to determine whether thyroid hormone levels are predictive of cardiac remodeling following myocardial infarction and the prognosis in patients with STEMI receiving primary percutaneous coronary intervention.


Eligibility: Inclusion Criteria:
  -  with a confirmed STEMI diagnosis
  -  undergoing primary percutaneous coronary intervention (presenting <12h after symptom onset)
  -  patients agreed and provided informed consent
  Exclusion Criteria:
  -  past history of myocardial infarction or percutaneous coronary intervention or coronary artery bypass graft
  -  past history of heart failure (LVEF<40%) or myocardiopathy or atrial fibrillation
  -  past history of thyroid diseases, or were treated with amiodarone, dopamine, or corticosteroids before hospital admission
  -  contraindicating to cardiac magnetic resonance imaging

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Evaluating Mutations in MET and TP53 Among Patients Diagnosed With Squamous Cell Carcinoma

Summary: This study focuses on advanced lung and head and neck SCC tumours, with adjacent normal lung tissues. Biopsies will be performed in National University Health System, Singapore (NUHS) as part of participants' standard care. Patient blood was also required for extraction of cell free DNA (cfDNA) and genomic DNA (gDNA). Patients' medical records will also be reviewed for the purpose of this study.

Detailed description: Primary objective:
  To investigate the prevalence of MET and TP53 mutations, as well as HER2 and MET amplification, in lung and head and neck tumours, through prospective collection of tumour specimens in newly recruited patients.
  Secondary objectives:
  1. To distinguish the presence of somatic/germline MET and TP53 mutation in lung and head and neck tumours.
  2. To detect for amplifications of MET and/or HER2 genes in SCC samples.
  3. To investigate the association and interaction of cMet and HER2 in SCC tumours.
  4. To establish a prospective documation of clinical, histopathological, treatment and follow-up (clinic pathological) data of newly recruited patients.

Eligibility: Inclusion Criteria:
  1. Age 18 years or older
  2. Histologic or cytologic confirmation of metastatic squamous cell carcinoma of the lung or head and neck region
  3. No other active malignancy within the past 24 months
  4. Refractory disease
  Exclusion Criteria:
  1. Patient with other active malignancy within the past 24 months
  2. Unable or unwilling to provide signed informed consent

Relevance to patient case: not relevant
Patient case: 32-year-old male with dilated cardiomyopathy; genetic feature: LMNA

Clinical trial: Prevention of Graft-Versus-Host Disease in Patients With Hematologic Malignancies Who Are Receiving a Bone Marrow Transplant

Summary: RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Treatment with sirolimus, methotrexate, and cyclosporine may prevent this from happening.
  PURPOSE: Phase I/II trial to study the effectiveness of sirolimus plus methotrexate and cyclosporine in preventing graft-versus-host disease in patients with hematologic malignancies who are receiving a bone marrow transplant.

Detailed description: OBJECTIVES: I. Estimate the maximum tolerated dose of rapamycin that can be safely combined with standard methotrexate/cyclosporine prophylaxis for graft-versus-host disease (GVHD) in patients with hematologic disorders who have received a bone marrow transplant from a related donor who is mismatched for 1 HLA-A, -B, or -DR antigen in the GVHD direction.
  OUTLINE: This is a dose escalation study. Groups of 6-12 patients receive escalating doses of rapamycin until the maximum tolerated dose of rapamycin given in combination with methotrexate/cyclosporine is determined. All patients receive cyclosporine from the day prior to transplant until day 50 post-transplant; the dose is then tapered over 130 days. Methotrexate is given on days 1, 3, and 6 post-transplant. Rapamycin is given every other day, days 7-59. Bone marrow transplantation occurs on day 0. Patients may not receive concurrent therapy with agents that could interfere with rapamycin metabolism, intravenous lipids, FK506 or other immunosuppressive agents (prednisone allowed), NSAIDs, or other cytotoxic agents. Patients are followed at 6 months for 2 years, then annually.
  PROJECTED ACCRUAL: 12-36 patients will be accrued over 1-2.5 years.

Eligibility: DISEASE CHARACTERISTICS: See General Eligibility Criteria
  PATIENT CHARACTERISTICS: Age: 13 and over Performance status: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No cardiac disease No clinically significant cardiac abnormality No ischemia No recent injury on EKG Other: No intolerance or unresponsiveness to rapamycin No hypersensitivity to macrolide antibiotics, e.g., erythromycin, azithromycin, clarithromycin No requirement for medications that may significantly affect rapamycin metabolism, i.e.: Carbamazepine Ketoconazole Primidone Cimetidine Nicardipine Rifampin Diltiazem Phenobarbital Valproic acid Erythromycin Phenytoin Verapamil No uncontrolled systemic infection No pregnant or nursing women Negative pregnancy test required of fertile women Effective contraception required of fertile patients during and for 3 months after study Able to tolerate less than 400 mL of liquid oral intake
  PRIOR CONCURRENT THERAPY: At least 1 week since any investigational drug

Relevance to patient case: not relevant
Patient case: 32-year-old male with dilated cardiomyopathy; genetic feature: LMNA

Clinical trial: Idiopathic Dilated Cardiomyopathy

Summary: To determine the familial occurrence and pathogenesis of idiopathic dilated cardiomyopathy.

Detailed description: BACKGROUND:
  In 1987 idiopathic dilated cardiomyopathy was a disorder of unknown cause that directly affected one or both cardiac ventricles in a diffuse or multifactorial fashion, and that produced heart failure, at least in some patients. Although a viral etiology had been proposed, dilated cardiomyopathy could be associated with numerous genetic and non-genetic diseases. However in 1987, the role of genetic factors was not known in humans. Although the condition was usually dismissed as sporadic, numerous families with multiple affected members have been observed.
  The role of atrial natriuretic peptide levels in the pathogenesis or progression of idiopathic dilated cardiomyopathy was just beginning to be explored in 1987. Although Syrian hamster studies did not suggest a genetic deficiency as the primary cause of dilated cardiomyopathy in that model, it was thought possible that ANP production or levels were somehow involved in how the myocardium responds in idiopathic dilated cardiomyopathy patients.
  DESIGN NARRATIVE:
  Eligible patients were interviewed and asked whether any first-degree relatives were willing to participate. If family members participated, a three generation pedigree was constructed and first-degree relatives contacted. The relatives were interviewed for a medical history and medical records from other institutions were reviewed. Each family member had a brief cardiovascular examination, a 12-lead electrocardiogram and 2-dimensional, M-mode, and Doppler echocardiogram. Blood was drawn for determination of atrial natriuretic peptide (ANP) levels. The contributions of variability in age, sex, drug use, smoking, and other concomitants to variability in ANP and echocardiographic data were estimated. After removing these sources of variability, the strength of similarity among family members was assessed. The relative contributions of genes and shared environments to the similarity among family members were estimated.
  Heterogeneity in the mean levels of echocardiographic indices and ANP levels, familial aggregation and etiology of aggregation were assessed between families with familial idiopathic dilated cardiomyopathy and families with non-familial idiopathic dilated cardiomyopathy.
  The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.

Eligibility: No eligibility criteria

Relevance to patient case: not relevant
Patient case: 32-year-old male with dilated cardiomyopathy; genetic feature: LMNA

Clinical trial: Epidemiology of Idiopathic Dilated Cardiomyopathy (Washington, DC Dilated Cardiomyopathy Study)

Summary: To identify risk factors for idiopathic dilated cardiomyopathy and to examine prognostic factors over a follow-up period of two to three years.

Detailed description: BACKGROUND:
  Idiopathic dilated cardiomyopathy is an often fatal cause of heart failure in young adults which is characterized by dilatation of the ventricles, increased myocardial mass, and impairment of systolic function. Dilated cardiomyopathy is more common than hypertrophic and restrictive cardiomyopathy, and the symptoms and physical signs are those of left-sided and eventually right-sided heart failure. Histologic findings in the condition include nonspecific interstitial myocardial fibrosis and myocyte hypertrophy. Despite the large number of systemic or generalized disease processes which have been associated with secondary dilated cardiomyopathy, the majority of cases are idiopathic. Mortality rates from cardiomyopathy have increased dramatically since 1970, and in 1990 over 10,000 deaths annually were attributed to cardiomyopathy in the United States.
  DESIGN NARRATIVE:
  The study had a prospective case-control design. Medical records of possible cases of idiopathic dilated cardiomyopathy who were discharged from five Washington, D. C. acute care hospitals over a two year period were abstracted so that standard diagnostic criteria could be applied. Two neighborhood controls were identified for each case. Cases and controls were matched on five year age intervals, sex, and telephone exchange. Cases were contacted annually during the two to three year follow-up period to determine vital status. The study determined whether the reported association between idiopathic dilated cardiomyopathy and asthma could be confirmed and the possible role of asthma medications, cigarette smoking, moderate alcohol consumption, and diabetes mellitus in the etiology of idiopathic dilated cardiomyopathy. The role of hypertension was also studied.. Statistical analysis consisted of case-control comparisons using conditional logistic regression techniques, and survival analyses using Kaplan-Meier curves and proportional hazards models.
  The study was also known as the Washington, D.C. Dilated Cardiomyopathy Study. Dr. Coughlin started his research at Georgetown University in Washington, D.C. and transferred to Tulane University.
  The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.

Eligibility: No eligibility criteria

Relevance to patient case: not relevant
Patient case: 32-year-old male with dilated cardiomyopathy; genetic feature: LMNA

Clinical trial: Genetic Study of the FBN1 Gene and Fibrillin-1 Abnormalities in Choctaw Native Americans and Other Patients With Systemic Sclerosis

Summary: OBJECTIVES: I. Determine whether defects in fibrillin-1 cellular processing are present in the tsk1 mouse model that carries a known FBN1 gene rearrangement and in a population of Choctaw Native American patients with systemic sclerosis who have a strong genetic predisposition to the disease.
  II. Determine the ultrastructural features of fibrillin-1 in these patients. III. Screen the FBN1 gene for mutations beginning at the regions homologous to the tsk1 duplication and latent transforming growth factor binding proteins in these patients and in an unaffected Choctaw control group.
  IV. Determine the correlation between fibrillin-1 abnormalities and clinical presentation, autoantibodies, and ethnicity.

Detailed description: PROTOCOL OUTLINE:
  Patients undergo punch skin biopsy obtained from the upper arm or back. Studies of fibrillin-1 synthesis and cellular processing, and FBN1 mutational analysis, linkage analysis, and genetic mapping are performed on the tissue samples. Patients from all major US ethnic groups (Caucasian, Hispanic, African Americans) will be recruited for the study in the next 2 years.

Eligibility: PROTOCOL ENTRY CRITERIA:
  --Disease Characteristics--
  Diagnosis of systemic sclerosis in accordance with the American College of Rheumatology preliminary criteria
  Positive for systemic sclerosis antibodies (e.g., anticentromere, antitopo, antifibrillarin, or antiRNA polymerase)

Relevance to patient case: not relevant
Patient case: 32-year-old male with dilated cardiomyopathy; genetic feature: LMNA

Clinical trial: Estrogen, Cytokines and Heart Failure in Women

Summary: To determine the effects of estrogen therapy on postmenopausal women with congestive heart failure.

Detailed description: BACKGROUND:
  Congestive heart failure (CHF) is a leading cause of morbidity, mortality, and hospitalization in women. The increase in mortality suggests that postmenopausal estrogen loss may alter the phenotypic expression of CHF. Because estrogen is a potent in vitro inhibitor of pro-inflammatory cytokines (e.g., TNFa, IL-1B, IL-6), which are re-expressed by the failing myocardium in patients with CHF and are related to an adverse prognosis, the study postulates that estrogen replacement will improve the outcome of postmenopausal women with CHF.
  DESIGN NARRATIVE:
  The randomized, double blind study was conducted in 166 postmenopausal women with congestive heart failure due to idiopathic (i.e.nonischemic) dilated cardiomyopathy and NYHA class II or III symptoms on either combined estrogen and progestin or placebo. Women maintained their then current congestive heart failure medications for six months. Three outcomes were measured: 1) Congestive heart failure severity/functional capacity quantified by maximum oxygen consumption during metabolic stress testing; 2) Left and right ventricular remodeling quantified by electron bean CT scan; 3) quality of life assessment by the Minnesota Living with Heart Failure and Kansas City cardiomyopathy questionnaires. In addition, measurements were made of pro-inflammatory markers, that had been demonstrated to be elevated in congestive heart failure to assess whether hormone replacement therapy reduced them.
  The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.

Eligibility: Postmenopausal women with NYHA Class II or Class III congestive heart failure due to idiopathic dilated cardiomyopathy.

Relevance to patient case: not relevant
Patient case: 32-year-old male with dilated cardiomyopathy; genetic feature: LMNA

Clinical trial: Mapping Novel Disease Genes for Dilated Cardiomyopathy

Summary: To identify new dilated cardiomyopathy genes by genetic linkage and mutational analyses.

Detailed description: BACKGROUND:
  Dilated cardiomyopathy (DCM) is a heritable, genetically heterogeneous disorder causing congestive heart failure. Current medical therapy has minimal impact on prognosis and cardiac transplantation is the only definitive treatment for end-stage disease. The molecular and cellular mechanisms underlying DCM are poorly defined, but the importance of single gene defects in disease pathogenesis is becoming increasingly apparent.
  DESIGN NARRATIVE:
  The genetic epidemiology study will identify novel dilated cardiomyopathy genes using genetic linkage and mutational analyses. The first aim is to determine the chromosomal location of novel familial dilated cardiomyopathy genes. This will be accomplished by genome-wide genotyping and genetic linkage analyses in three large families with autosomal dominant dilated cardiomyopathy. Previously identified dilated cardiomyopathy genes have been excluded in these families. The second aim is to identify mutations in novel genes that cause familial dilated cardiomyopathy by linkage and sequence analyses of candidate genes mapping to dilated cardiomyopathy loci. Once novel genes for familial dilated cardiomyopathy are identified, the third aim will be to determine the role of these genes in a large cohort of unrelated patients with familial and sporadic dilated cardiomyopathy. High throughput DNA sequence analyses will be performed to identify additional inherited and de novo mutations.

Eligibility: No eligibility criteria

Relevance to patient case: not relevant
Patient case: 32-year-old male with dilated cardiomyopathy; genetic feature: LMNA

Clinical trial: Cohorts and Collections: Clinical and Genetic Study of Parkinson's Disease and Epilepsies

Summary: The DNA and Cell Bank of Instituts Federatifs de Recherche (IFR) of Neurosciences has been running for the last 15 years at the Institut National de la Santé Et de la Recherche Médicale (INSERM) Unit 679 (former unit 289). Since its creation, this structure has been the support of research projects in genetics for neurological and psychiatric disorders. The cohorts established have led to discoveries in monogenic disorders, such as cerebellar ataxias, spastic paraplegias, frontotemporal dementias, epilepsies, Parkinson’s and Alzheimer’s disease, Charcot-Marie-Tooth disease and related entities. The research projects based on the study of the genetic bases in Parkinson’s disease and epilepsies are especially developed for this grant.
  Concerning Parkinson’s disease, the project is based on the extension of the existing cohort throughout the French Parkinson’s Disease Study Group network. Concerning epilepsies, this project is the occasion to build this network with the constitution of a new cohort.
  The specific aims of the scientific projects are the following for Parkinson’s disease:
  -  to evaluate the frequency, the nature and the phenotype associated with parkin mutations in familial or sporadic forms of the disease, according to the age at onset, and
  -  to identify the genetic susceptibility factors in Parkinson’s disease with the study of affected sibpairs and with case/controls association studies.
  For epilepsies, the aims are:
  -  to evaluate the frequency, the nature and the phenotype associated with SCN1A, SCNab and GABR2 gene mutations in familial or sporadic forms of the affection associated with febrile seizures, and
  -  to search for an intervention SCN1A, SCN1B and GABRG2 as susceptible genes in these forms of epilepsies.


Eligibility: Inclusion Criteria:
  -  Patients presenting with Parkinson's disease, with a family history or not,
  -  Minors presenting clinical signs of the disease,
  -  Controls (without signs of the disease), matched by sex and age with the patients,
  -  Relatives for the familial cases,
  -  Patients presenting with an epilepsy episode (myoclonic epilepsy of the newborn, with febrile seizures, of the frontal lobe)
  Exclusion Criteria:
  -  Lack of signed informed consent

Relevance to patient case: not relevant