araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: Effects of Mexiletine on Colonic Transit in a Patient With Irritable Bowel Syndrome - Constipation (IBS-C)

Summary: To understand if Mexiletine will restores normal colonic motility in a patient with irritable bowel syndrome - constipation (IBS-C) and a genetic mutation in SCN5A.

Detailed description: To understand if Mexiletine will restore normal colonic motility in a patient with a missense mutation in SCN5A, which encodes a voltage-sensitive sodium channel NaV1.5 as it is known to rescue certain expression defects of NaV1.5 in vitro.

Eligibility: Inclusion Criteria:
  -  Established IBS diagnosis with a known A997T mutation in NaV1.5T
  Exclusion Criteria:
  -  Normal 48-hour baseline transit study
  -  Current use of mexiletine
  -  Inability to stay in Rochester for 9 days for testing
  -  Known allergy to mexiletine
  -  Inability to complete daily diary
  -  Taking a medication known to affect myotonia, had a coexisting neuromuscular disease, or had another serious medical illness including second- or third-degree heart block, atrial flutter, atrial fibrillation, ventricular arrhythmia, history of cardiac arrhythmia requiring medication, congestive heart failure, symptomatic cardiomyopathy, or symptomatic coronary artery disease
  -  Inability to withdraw medications known to interact with mexiletine. Patient is currently not on any of these medications

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

Clinical trial: Use of GM-CSF Supplemented IVF Medium in Patients With Recurrent Implantation Failure

Summary: The purpose of this study is to determine whether in Assisted Reproductive Technologies the use of culture medium supplemented with GM-CSF, a growth factor working on stem cells, may improve the embryo implantation in patients experiencing recurrent implantation failure in IVF cycles.

Detailed description: In Assisted Reproductive Technologies the rate of pregnancy for cycle and the implantation rate remain low nevertheless the improvement in the last years. In particular there are a group of patients, in young reproductive age, experiencing recurrent implantation failure, nevertheless the good embryos produced and transferred. Recently, it has been showed that culture medium supplemented with GM-CSF, may improve the embryo outcomes in IVF. In this trial the investigators will test the potential benefits of this culture medium on embryos of patients experiencing recurrent implantation failure. 100 women with recurrent implantation failure, at least three failed previous IVF attempts with at least 8 good embryos transferred no more than 40 years old will be selected. These patients will be assigned to two arms, one experimental and one other of control by a computer generated sequence. After the oocyte retrieval and fertilization by ICSI procedure, the fertilised oocyte (2PN)will cultured with the GM-CSF supplemented culture medium (EmbryoGen, Origio, Denmark), or in normal culture in micro drop of 30microliters under oil until the day of transfer (day three or 8 cells sage embryos). A maximum of three embryos will be transferred. The pregnancy rate the implantation rate will be the outcomes considered

Eligibility: Inclusion Criteria:
  -  woman age 40 years old or less,
  -  3 or more consecutive previous failed IVF cycles with a total of at least 8 good embryos replaced in uterus
  Exclusion Criteria:
  -  chromosomal defects in the couple,
  -  metabolic diseases (diabetes, etc),
  -  other genetic diseases (thalassemia, cystic fibrosis, etc.)

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

Clinical trial: Long Term Prophylactic Therapy of Congenital Long QT Syndrome Type III (LQT3) With Ranolazine

Summary: The purpose of this study is to determine whether ranolazine will reduce the risk of arrhythmic events in patients with long QT syndrome type 3.


Eligibility: Inclusion Criteria:
  -  Long QT patients with genetic confirmation of carrier-status for the D1790G mutation in the SCN5A gene
  -  Corrected QT interval > 460 msec
  Exclusion Criteria:
  -  Need for therapy with medications that are potent or moderately potent CYP3A inhibitors (such as ketoconazole, diltiazem, verapamil, macrolide antibiotics or HIV protease inhibitors)

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

Clinical trial: Endometrial Injury and IVF Outcome Parameters in Patients With Failed IVF Cycles

Summary: The iatrogenic induction of local endometrial injury caused through hysteroscopy or pipelle sampling in the preceding non- transfer cycle improves the IVF outcome parameters in patients with previous IVF failures.

Detailed description: Endometrial injury was preformed either through hysteroscope during office hysteroscopy through the non touch technique or through pipelle biopsy in the early follicular phase (days 5 to 9) in the preceding cycle of the IVF treatment.

Eligibility: Inclusion Criteria:
  -  Personal history of 2 or more failed IVF/ICSI cycles (RIF)
  -  Age</= 42 years
  -  Good response with good quality embryos in previous attempts (>2)
  Exclusion Criteria:
  -  Personal history of endometrial tuberculosis/ antituberculous treatment
  -  Sonographically detected hydrosalpinges
  -  Intramural fibroids distorting the endometrial cavity, submucous myomas or Asherman's syndrome
  -  Thrombophilia

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

Clinical trial: Compassionate Use of Stiripentol in Dravet Syndrome

Summary: Compassionate use of Stiripentol in Dravet Syndrome. This is a treatment protocol, not a research study, therefore children will only be monitored on a clinical basis for seizure improvement predominantly by parent and caregiver report.

Detailed description: This is a treatment protocol for compassionate use, not a research study, therefore children will only be monitored on a clinical basis for seizure improvement predominantly by parent and caregiver report.

Eligibility: Children with genetic confirmation of Dravet syndrome (a documented sodium channel, voltage-gated, type I, alpha subunit (SCN1A) mutation) or clinical confirmation of Dravet syndrome by two pediatric neurologist will be considered to have Dravet syndrome. In order to enter the treatment protocol there will be documented treatment failure of at least two therapeutic anticonvulsants excluding Na channel blockers. Anticonvulsants that are Na channel blockers such as carbamazepine and lamotrigine as known to provoke seizures in this patient population.

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

Clinical trial: Investigating Hereditary Cardiac Disease by Reprogramming Skin Cells to Heart Muscle

Summary: Hereditary cardiac arrhythmias (genetically caused disturbances of heart rhythm) are life threatening conditions affecting otherwise healthy young individuals. Due to the inaccessibility of heart tissue, the abnormal electrical current(s) in the heart cells causing the rhythm disturbance can be difficult to study in detail and therefore in many cases remain untreatable. The investigators propose to study heart cell electrical function from such patients by reprogramming skin cells to become stem cells and then differentiating them to heart muscle cells.
  The hypothesis of the study is that the differentiated cardiac cells will display electrical abnormalities dependent on the mutation causing the disease. These abnormalities can therefore provide a clue as to the nature of the mutation causing the disease or information about its effective management


Eligibility: Inclusion Criteria:
  -  Clinical features of Brugada Syndrome (ECG findings)
  -  mutation positive or mutation negative
  -  Idiopathic ventricular fibrillation
  Exclusion Criteria:
  -  not able to give informed consent
  -  Age less than 18 years
  -  clinical diagnosis ambiguous

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

Clinical trial: Gadobutrol/Gadavist-enhanced Cardiac Magnetic Resonance Imaging (CMRI) to Detect Coronary Artery Disease (CAD)

Summary: Participants being evaluated for suspected or known Coronary artery Disease (CAD) based on signs and/or symptoms, will be invited to participate in the study. The duration for a participant in the study may range from 2 days to 4-6 weeks. One to four visits to the study doctor will be required.
  This study will investigate the diagnostic results of gadobutrol-enhanced Cardiac Magnetic Resonance Imaging (CMRI) images regarding the detection (sensitivity) and exclusion (specificity) of coronary artery disease utilizing a uniform image acquisition software. The CMR images will be tested either against the results from routine clinical Coronary Angiography (CA) or those from Computed Tomography Angiography (CTA), which is used as the standard of reference. The CA/CTA may have been performed up to 4 weeks prior to enrollment or be scheduled up to 4/6 weeks after the study.
  CMRI and CA/CTA images will be collected for an independent image review (blinded read).


Eligibility: Inclusion Criteria:
  -  Male or female participants aged ≥18 years
  -  Participants with suspected or known CAD based on signs and/or (typical or atypical) chest pain who have routine CA without intervention or CTA within 4 weeks around gadobutrol-enhanced CMRI
  -  Willingness to undergo stress/rest CMRI and to follow directions and complete all study procedures
  -  Women of childbearing potential (e.g. age < 60y, no history of surgical sterilization or hysterectomy): use of contraception and a negative pregnancy test
  Exclusion Criteria:
  -  Suspected clinical instability or unpredictability of the clinical course during the study period
  -  Contraindication to the cardiac MRI examination (e.g. inability to hold breath; severe claustrophobia, metallic devices such as pace makers)
  -  History of severe allergic or anaphylactoid reaction to any allergen including drugs and contrast agents according to the investigator's assessment / judgment
  -  Estimated glomerular filtration rate (eGFR) value <30 mL/min/1.73 m^2 derived from a serum / blood creatinine result within 2 weeks prior to gadobutrol injection. Any participant on hemodialysis or peritoneal dialysis is excluded from enrollment.
  -  Acute renal insufficiency
  -  Coronary artery bypass grafting (CABG)
  -  Acute myocardial infarction (< 14 days prior to inclusion), unstable angina / acute coronary syndrome, severe congestive heart failure
  -  Irregular heart rhythm
  -  Condition that precludes the safe administration of pharmacological stressor according to the respective approved label such as sinus node disease, 2nd or 3rd degree atrioventricular block, obstructive lung disease

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

Clinical trial: Carfilzomib for the Prevention of Graft Versus Host Disease

Summary: The aim of this study is to evaluate the safety and efficacy of Carfilzumib, which is a novel biological agent used in the treatment of multiple myeloma in preventing graft-versus-host disease, after stem cells transplantation from unrelated donors.


Eligibility: Inclusion Criteria:
  1. Patients with MDS/AML
  2. 18 years or older and willing and able to comply with the protocol requirements.
  3. LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
  4. Patients undergoing 8-10/10 HLA matched unrelated and unmanipulated PBSC transplantation
  5. Patients conditioned with reduced intensity or reduced toxicity conditioning i.e. Fludarabine combine with Treosulfan or 2-4 days of I.V Busulfan.
  6. Patients must sign written informed consent.
  7. Adequate birth control in fertile patients.
  Exclusion Criteria:
  1. Patients undergoing other type of transplantation or with other type of basic disease other than AML or MDS.
  2. Patients with respiratory failure (DLCO < 30%).
  3. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention.
  4. Patients with > grade II liver renal toxicity.
  5. Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate
  6. Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit
  7. Creatinine > 2.0 mg/dl
  8. ECOG-Performance status > 2
  9. Uncontrolled infection
  10. Pregnancy or lactation
  11. CNS disease involvement
  12. Pleural effusion or ascites > 1 liter.

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

Clinical trial: Worm Study: Modifier Genes in Sudden Cardiac Death

Summary: Quest for modifier genes associated with ventricular arrhythmias in presence of a cardiac sodium channel gene (SCN5A-delPhe1617) mutation.

Detailed description: In a large Dutch SCN5A founder population with malignant ventricular arrhythmias, the investigators aim to identify genetic modifiers by means of whole-exome sequencing and to establish a comprehensive genotype-phenotype correlation, focussing on clinical and cellular electrophysiological characteristics and neurocardiac modulation.

Eligibility: Inclusion Criteria (mutation carrier group):
  -  Age ≥ 18 years.
  -  Heterozygous or homozygous carriership of SCN5A-delPhe1617.
  -  Confirmed kinship to the founder population by haplotype analysis using predefined microsatellite markers.
  -  Written informed consent.
  Inclusion Criteria (non-mutation carrier group):
  -  Age ≥ 18 years.
  -  Non SCN5A-delPhe1617 genotype.
  -  Confirmed kinship to the Founder Group by haplotype analysis using predefined microsatellite marker.
  -  Written informed consent.
  Inclusion criteria Spouse Group
  -  Age ≥ 18 years.
  -  Biological parent of SCN5A-delPhe1617 positive subject participating to the Worm Study, and not belonging to study group 1 or 2.
  -  Written informed consent.
  Exclusion Criteria:
  -  Age ≥ 18 years.
  -  Biological parent of SCN5A-delPhe1617 positive subject participating to the Worm Study, and not belonging to study group 1 or 2.
  -  Written informed consent.

Relevance to patient case: definitely relevant
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: AnalyST & Brugada Syndrome - Feasibility Study

Summary: Brugada syndrome is characterized by a ST shift on the surface ECG, and a specific morphology of the Twave. This ECG abnormality is called a type 1-ECG, and is variable in time. Patients presenting a Brugada syndrome are exposed to sudden cardiac death, although it's difficult to predict patients at high risk. It is suspected that the type 1-ECG burden might be correlated to the ventricular fibrillation risk of these patients, but there is no mean to record the ECG over a long period of time.
  The objective of the study is to evaluate the correlation between ST elevation on the electrocardiogram (ECG) and ST shift on the intracardiac electrograms (EGM) recorded with the AnalyST ICD, to assess the ability of the device to detect the type 1-ECG. Patients enrolled in the study are patients already implanted with a defibrillator for their Brugada syndrome. During an Ajmalin test, which unmasks the type 1-ECG, both intracardiac EGM and surface ECG will be compared to assess the detection of the typical ST-shift by the ICD.

Detailed description: To evaluate the correlation between ST elevation on the ECG and ST shift on the intracardiac EGM recorded with the AnalyST ICD, patients enrolled will have to be already diagnosed as presenting the Brugada Syndrome. They will undergo an ajmaline test, to unmask the type 1-ECG, characteristic from the Brugada syndrome.During the test, both surface ECG and intracardiac signal will be continuously recorded; then the signals will be compared in terms of amplitude of the ST shift, duration of the shift, and recovery period.

Eligibility: Inclusion Criteria:
  -  Patients with Brugada syndrome and previous positive Ajmalin test

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

Clinical trial: Detection of SLN in Patients With Endometrial Cancer Undergoing Robotic Assisted Staging: Comparison of ISB and ICG

Summary: The investigators hypothesis is that if sensitivity and specificity are found to be significantly higher than the current reports with Technesium-99 and ISB colorimetric dye, SLN biopsies might allow omission of full lymphadenectomy in lower-risk cases, thereby limiting peri-operative morbidity. SLN biopsies might also improve the detection of metastatic disease, essentially lowering the recognized false-negative rate of standard lymphadenectomy analyzed by routine H&E pathologic analysis.

Detailed description: The study objective is to compare two sentinel lymph node detection technologies [fluorescence imaging and Indocyanine Green (ICG) dye verses standard laparoscopic colorimetric analysis using Isosulfan Blue (ISB) dye] for sensitivity and specificity of detecting metastatic disease in pelvic lymph nodes of women with endometrial cancer undergoing robotic-assisted laparoscopic hysterectomy and lymphadenectomy. The following three specific aims would be addressed in this research proposal:
  Specific Aim 1: To determine the ability of mapping bilaterally pelvic SLN in women with endometrial cancer undergoing robotic-assisted laparoscopic staging comparing two different methods (i.e., comparing the combination of colorimetric analysis-ISB dye + fluorescence imaging-ICG dye vs. colorimetric analysis-ISB dye alone).
  Specific Aim 2: To estimate the negative predictive value (NPV) of pelvic SLN in endometrial cancer with respect to predicting nodal metastasis.
  Specific Aim 3: To evaluate the ability of sentinel lymph nodes to increase the detection of metastatic disease through ultra-sectioning and immuno-histochemical (IHC) staining by comparing IHC results and standard hematoxolin and eosin (H&E) results.

Eligibility: Inclusion Criteria:
  1. The patient must be ≥18 and ≤85 years of age.
  2. The patient must be female.
  3. The patient must be willing and able to provide informed consent.
  4. The patient is willing and able to comply with the study protocol.
  5. The patient has endometrial cancer and is scheduled for robotic hysterectomy and lymphadenectomy.
  6. The patient agrees to follow-up examinations out to 6-weeks post-treatment
  Exclusion Criteria:
  1. The patient is not a candidate for robotic assisted hysterectomy and lymphadenectomy.
  2. The patient has known or suspected allergies to iodine, ICG or ISB.
  3. The patient has hepatic dysfunction confirmed by elevated liver function studies (i.e., hepatic enzyme SGOT, SGPT or Bilirubin > 2 x normal (based on reference values from the laboratory used by the patient)

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

Clinical trial: The Mechanism of TCF7L2 and SLC30A8 on Antipsychotic-induced Metabolic Syndrome

Summary: Almost all of antipsychotics can induce metabolic syndrome,Genetic factors play a key role in the development of metabolic syndrome,TCF7L2 and SLC30A8 are strongestly correlated with metabolic syndrome.Moreover,Antipsychotics have an effect on the expression of TCF7L2 and SLC30A8 genes.It indicates the variations of TCF7L2 and SLC30A8 play an important part in the development of antipsychotics-induced metabolic syndrome.

Detailed description: -  In this study, we will determine the effect of olanzapine on the expression of TCF7L2 and SLC30A8.
  -  The relationship of the polymorphism of TCF7L2 and SLC30A8 with antipsychotic-induced metabolic syndrome in schizophrenia patients.

Eligibility: Inclusion Criteria:
  -  Clinical diagnosis of first episode schizophrenia
  -  Must be able to swallow tablets
  -  Take only one antipsychotics
  Exclusion Criteria:
  -  liver or renal or cardiovascular diseases
  -  pregnant or lactating women
  -  drug and alcohol dependence

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

Clinical trial: Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations.

Summary: Entrectinib (RXDX-101) is an orally available inhibitor of the tyrosine kinases TrkA (coded by the gene NTRK1), TrkB (coded by the gene NTRK2), TrkC (coded by the gene NTRK3), ROS1 (coded by the gene ROS1), and ALK (coded by the gene ALK). Molecular alterations to one or more of these targets are present in several different tumor types, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), prostate cancer, papillary thyroid cancer, pancreatic cancer, and neuroblastoma. Patients with locally advanced or metastatic cancer with a detectable molecular alteration in targets of interest may be eligible for enrollment.
  Phase 1 will assess safety and tolerability of entrectinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and efficacy will be assessed in the dose expansion portion of the study.


Eligibility: Key Inclusion Criteria:
  -  Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors that have a NTRK1, NTRK2, NTRK3, ROS1, or ALK molecular alteration.
  -  Measurable disease according to RECIST version 1.1.
  -  Prior cancer therapy is allowed, including crizotinib, ceritinib, and investigational drugs.
  -  Prior radiotherapy is allowed
  -  Patients with controlled asymptomatic central nervous system involvement are allowed.
  -  Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
  -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
  -  Adult patients age 18 years or older.
  -  Life expectancy of at least 3 months.
  Key Exclusion Criteria:
  -  Current participation in another therapeutic clinical trial.
  -  Prior treatment with entrectinib.
  -  History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds).
  -  History of additional risk factors for torsade de pointes (e.g., family history of long QT syndrome).
  -  Known active infections (bacterial, fungal, viral including HIV positivity).
  -  Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
  -  Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis.
  -  Peripheral neuropathy ≥ Grade 2.

Relevance to patient case: not relevant