araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: Personalized Chimeric Antigen Receptor T Cell Immunotherapy for Patients With Recurrent Malignant Gliomas

Summary: A pilot study to determine the safety and efficacy of chimeric antigen receptor T cell (autologous T cells transduced with a lentiviral vector expressing chimeric antigen receptor) personalized immunotherapy for patients with recurrent malignant gliomas based on the expression of tumor specific/associated antigens (EGFRVIII, IL13Rα2, Her-2, EphA2, CD133, GD2).


Eligibility: Inclusion Criteria:
  -  Voluntary informed consent for entry of trial;
  -  Age greater than 18 years, and less than 70 years;
  -  Pathologically confirmed recurrent malignant gliomas;
  -  Tumor cells from resected tissue must be available for antigen testing (EGFRvIII, IL13Rα2, Her-2, CD133, EphA2, GD2) and at least one of the targets should be tested positively by immunohistochemistry study;
  -  If the patient is on dexamethasone, the anticipated dose must be 4 mg/day or less for at least 5 days prior to apheresis.
  -  Patients must have a Karnofsky performance status of greater than or equal to 70.
  -  Life expectancy greater than 3 months;
  -  Participants with adequate organ function as measured by:
  1. White blood count greater than or equal to 2500/mm^3; platelets greater than or equal to 100,000/mm^3, hemoglobin greater than or equal to 10.0 g/dL; without transfusion or growth factor support
  2. Aspartate transaminase (AST), Alanine transaminase (ALT), gamma glutamyl transpeptidase (GGT), lactic acid dehydrogenase (LDH), alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin less than or equal to 2.0 mg/dL
  3. Serum creatinine less than or equal to 1.5 x upper limit of normal
  4. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) have to be within normal limits, unless the patient has been therapeutically anti-coagulated for previous venous thrombosis.
  Exclusion Criteria:
  -  Female subjects of reproductive potential who are pregnant or lactating;
  -  Previous treatment with any gene therapy products or other form immunotherapy;
  -  Uncontrolled active infection.
  -  Active or latent chronic hepatitis B [detectable hepatitis B surface antigen (HBsAg)] or active hepatitis C (positive serology [hepatitis C virus Ab]) infection.
  -  HIV infection;
  -  History of allergy or hypersensitivity to study product excipients (human serum albumin, Dimethyl sulfoxide, and Dextran 40);
  -  Currently enrolled in other clinical trials;

Relevance to patient case: not relevant
Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: MSC-Exos Promote Healing of MHs

Summary: Purpose: To assess the safety and efficacy of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) for promoting healing of large and refractory macular holes (MHs).
  Hypothesis: MSC and MSC-Exo therapy may promote functional and anatomic recovery from MH. MSC-Exo therapy may be a useful and safe method for improving visual outcomes of surgery for refractory MHs.

Detailed description: Based on the purpose and hypothesis,the participants with large and longstanding idiopathic MHs underwent vitrectomy, internal limiting membrane peeling, MSC or MSC-Exo intravitreal injection, and heavy silicon oil, air, 20% SF6, or 14% C3F8 tamponade. MSCs were isolated from human umbilical cord, and MSC-Exos were isolated from supernatants of MSCs via sequential ultracentrifugation. At the time of study enrollment, as well as physical examinations, best-corrected visual acuity (BCVA) and intraocular pressure will be measured and fundoscopy be performed. All diagnoses of MH are going to confirmed via spectral-domain optical coherence tomography (OCT), and the minimum linear diameter (MLD) of each MH will be measured parallel to the retinal pigment epithelium.The participants are going to be followed up for at least 6 months via BCVA measurement, fundoscopy, OCT, and physical examinations.

Eligibility: Inclusion Criteria:
  1.Clinical diagnosis of idiopathic macular hole whose diameter is greater than 400 microns
  Exclusion Criteria:
  1. Only one functional eye
  2. In other clinical trials.
  3. Other diseases which can affect visual acuity, such as cataract, diabetic retinopathy, glaucoma, corneal diseases, etc.
  4. Eye had undergone vitrectomy or scleral buckling, cataract surgery, Nd:YAG laser less than one month ago.
  5. Contralateral eye has poor prognosis than the study eye.
  6. Idiopathic or autoimmune uveitis history.
  7. Aphakic eye
  8. Physical condition is poor that can not keep prone position.
  9. Secondary macular lesions
  10. The equivalent spherical diopter of the study eye before any refractive correction or cataract surgery, which is greater than 6.0d or above 26mm of the ocular axis of the study eye.
  11. Intraocular pressure is higher than 25mmHg
  12. Within ocular inflammation, such as eye blepharitis, scleritis, keratitis and conjunctivitis.
  13. Systemic condition is poor, such as the poor control of diabetes and hypertension, myocardial infarction, cerebrovascular accident, renal failure and so on,and the researchers assessed those who are unable to complete the trail.

Relevance to patient case: not relevant
Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: Sevoflurane in Chronic Obstructive Pulmonary Disease Exacerbation

Summary: Prospective, open-label, single-center, study to investigate the effect of sevoflurane sedation compared to a propofol-controlled arm during COPD exacerbation requiring invasive mechanical ventilation in ICU.
  Primary outcome measure:
  Evolution of airway resistance before and after sevoflurane in COPD patients,
  Secondary outcomes measures:
  Respiratory mechanics (Maximum pressure, PEEPi and PEEPtot, trapped volume), Gas exchange by the help of blood gases, The heterogeneity of alveolar ventilation by electro-impedancemetry, Evolution of pulmonary inflammation, Trophicity and contractility of the diaphragm,


Eligibility: Inclusion Criteria :
  -  COPD exacerbation
  -  Invasive mechanical ventilation and sedation for a planned duration of at least 24 hours
  -  Consent
  -  Age ≥ 18 years
  -  Affiliation or beneficiary of a social security scheme
  Exclusion Criteria :
  -  Contraindication to the administration of sevoflurane (personal or family history of malignant hyperthermia, allergy or halogenated anesthetic accident, chronic myopathy, halogenated toxic hepatitis, uncontrolled intracranial hypertension, unexplained leukocytosis after anesthesia with a halogenated agent)
  -  Contraindication to the administration of propofol (known hypersensitivity to propofol, soy, peanut or any of the excipients of the emulsion, antecedent of Propofol Related Infusion Syndrome)
  -  Refusal of consent
  -  Guardianship
  -  Age < 18 years
  -  Pregnant or lactating woman

Relevance to patient case: not relevant
Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: Use of a Hand-held Digital Cognitive Aid in the Early Management of Simulated War Wounds.

Summary: Combat casualty care has proven to increase survival rate in military conflict by treating without delay the quickest-to-kill wounds. The French militaries are trained to the MARCHE RYAN acronym, an algorithm designed to help every soldiers provide simple treatment in order to bring the patient to the surgeon alive.
  Our first study (MAX, Lelaidier et al, BJA 2017) clearly showed that the use of a digital cognitive aid in the hand of the leader significantly improves the management of anaesthesia & intensive care emergencies (malignant hyperthermia, anaphylactic shock, acute toxicity of local anaesthetics, severe and symptomatic hyperkalaemia).
  The present study exclusively deals with the management of combat casualties with the same digital cognitive aid adapted for MARCHE RYAN algorithm.

Detailed description: In a first study (MAX, BJA 2017, Lelaidier et al) the investigators designed a digital cognitive aid (MAX for Medical Assistant eXpert) under the form of a smartphone application including 5 scenarios of anaesthesia and intensive care crises (malignant hyperthermia, anaphylactic shock, acute toxicity of local anaesthetics, severe and symptomatic hyperkalaemia, ventricular fibrillation), designed to be used in the hand of the leader managing the situations. Technical and non-technical skills were improved in 4 out of 5 scenarios.
  Combat casualties are dealt with a stereotyped management in the French army, and all soldiers learn the algorithm (acronym) designed for this purpose, the MARCHE RYAN. Situations requiring the use of the MARCHE RYAN are extremely stressful (on the battlefield, performed by non-medical personal, often on a comrade).
  The present study exclusively deals with the management of combat casualties with the digital cognitive aid MAX adapted for MARCHE RYAN algorithm.

Eligibility: Inclusion Criteria:
  -  Soldiers
  -  already trained in Combat Care level 2, under training for external operations.
  Exclusion Criteria:
  -  none

Relevance to patient case: not relevant
Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: Dopamine and Muscle Function in the Heat

Summary: our goal is to study the effects of dopamine activity, using Ritalin ingestion, on neuromuscular function over the course of a progressive heating and cooling protocol developed in our lab. We hypothesize that Ritalin will minimize the previously reported progressive impairment in neuromuscular function with hyperthermia compared to placebo, suggesting that dopamine activity preserves neuromuscular capacity with hyperthermia.

Detailed description: Increased core temperature (hyperthermia) has been associated with impaired neuromuscular performance, with the majority of research suggesting that the observed fatigue is related to the central nervous system. Small doses of Ritalin has been used to study how changes in dopamine activity affects exercise capacity in the heat. This study found that 20 mg of Ritalin had no effect on exercise capacity in a thermoneutral environment of 18°C. However, when in a hot (30°C) environment, the Ritalin resulted in a 16% improvement in finishing time compared to the placebo trial. Interestingly, the higher output during the Ritalin-hot condition also resulted in higher rates of heat production and a higher (~0.6°C) core temperature, suggesting that dopamine enabled greater voluntary tolerance of hyperthermia. This matches recent work from our own work showing that motivational skills training increased both exercise tolerance and final core temperature, and it is possible that dopamine activity played a role in this improvement.
  Ultimately, fatigue is shown in an inability to sustain muscular force. However, the role of dopamine activity on neuromuscular function (e.g., central activation and recruitment of muscle) during hyperthermia is unknown. One study reported that 20 mg of Ritalin did not alter neuromuscular function, but this study was done without thermal stress.
  Therefore, our goal is to study the effects of dopamine activity, using Ritalin ingestion, on neuromuscular function over the course of a progressive heating and cooling protocol developed in our lab. We hypothesize that Ritalin will minimize the previously reported progressive impairment in neuromuscular function with hyperthermia (5, 7) compared to placebo, suggesting that dopamine activity preserves neuromuscular capacity with hyperthermia.

Eligibility: Inclusion Criteria:
  -  High aerobic fitness (>55 mL/kg/min maximal aerobic capacity)
  Exclusion Criteria:
  -  diagnosed cardiovascular, respiratory and/or neuromuscular disease, prescription of Ritalin or any drugs for hyperactivity within the past 1 year, any current prescription medication (except for asthma/allergy inhalers), any contraindications to Ritalin.

Relevance to patient case: not relevant
Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: Macular Hole After Diabetic Vitrectomy

Summary: To present the clinical characteristics and rational treatment of macular hole (MH) after the diabetic vitrectomy (DV) in patients with proliferative diabetic retinopathy (PDR).

Detailed description: All patients had received initial vitrectomy to treat complications of PDR. Recruited patients were divided to two groups: the persistent MH group, who had MH before the primary DV (group 1); and the newly-developed MH group, who developed MH after a successful primary DV (group 2). The patients' demographic data, records of ophthalmological examinations, and surgical procedures were collected, including best-corrected visual acuity before and after each operation, fundus changes, as well as MH repairing techniques. The extent of fibrovascular proliferation(FVP) was separated into four grades based on the severity of vitreoretinal adhesion : multiple-point adhesions with or without one site plaque-like broad adhesion (grade 1), broad adhesions in more than one but fewer than three sites, located posterior to the equator (grade 2), broad adhesions in more than three sites, located posterior to the equator or extending beyond the equator within one quadrant (grade 3), and broad adhesions extending beyond the equator for more than one quadrant (grade 4). The extent of retinal detachment (RD) was classified into "within the arcade" or "beyond the arcade". The macular structure was evaluated by optical coherence tomography (OCT). All patients had a follow-up duration of more than three months after the final surgical procedures.
  Three different surgical techniques were used to treat MH: standard internal limiting membrane (ILM) peeling, inverted ILM flap insertion into the MH, and lens anterior or posterior capsular flap insertion into the MH. The indication(s) for each technique were:
  standard ILM peeling was performed if no ILM peeling had been done in the previous surgery, and the MH size was less than 500um in an attached retina; inverted ILM flap insertion was performed if no ILM peeling had been done in the previous surgery, with a detached retina; lens anterior capsule flap insertion was performed if cataract surgery was performed in the same setting with no ILM tissue available; lens posterior capsule flap insertion was performed in a pseudophakic eye with no ILM tissue available. Only descriptive statistics was obtained.

Eligibility: Inclusion Criteria:
  -  Proliferative diabetic retinopathy patients presenting with macular hole after primary diabetic vitrectomy
  -  The persistent MH group after surgery, who had MH before the primary DV
  -  Newly-developed MH group, who developed MH after a successful primary diabetic retinopathy
  Exclusion Criteria:
  -  Patients with peripheral breaks
  -  Patients with macular hole before surgery, which closed after primary diabetic retinopathy
  -  Missing clinical data

Relevance to patient case: not relevant
Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: Effects of Aromatase Inhibitor Therapy on Muscle Function

Summary: This is a pilot study designed to examine changes in muscle function after Aromatase Inhibitor (AI) therapy, at both the molecular and clinical level.


Eligibility: Inclusion Criteria:
  1. Age ≥ 18 years
  2. Post-menopausal
  3. Diagnosis of ductal carcinoma in situ (DCIS) or stage I, II, or III ER positive breast cancer
  4. Plan to initiate an AI per treating physician.
  5. Completion of all primary therapy for breast cancer, including surgery, radiation, and chemotherapy (should be completed 14 days or more prior to obtaining the baseline muscle biopsy). Ongoing HER2 targeted therapy with trastuzumab and/or pertuzumab is allowed. Ongoing neratinib therapy is not allowed.
  6. Body weight less than 350 lbs., as dictated by the weight limit for DXA (dual energy x-ray absorptiometry) scanner
  7. Must be willing to undergo muscle biopsy at baseline and after 24 weeks of AI therapy
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at the time of study enrollment
  9. Informed consent and authorization of the release of health information must be obtained according to institutional guidelines
  Exclusion Criteria:
  1. Unwilling to co-enroll into the FIT core study
  2. Diagnosis of severe osteopenia or osteoporosis, defined as a bone mineral density of ≥ 2.0 standard deviations below the young adult female reference mean (T score)
  3. Diagnosis of other disorder affecting bone function or turnover, such as Paget's disease, renal osteodystrophy, parathyroid disorders, or vitamin D deficiency/osteomalacia
  4. Prior history of non-traumatic, fragility bone fracture
  5. Any muscle or neuromuscular disorder affecting muscle function, such as muscular dystrophy, myositis, or amyotrophic lateral sclerosis
  6. Any condition precluding power protocol participation (i.e. exertion on a stationary bicycle), including: New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled angina, myocardial infarction in the prior 12 months, orthopedic surgery in the previous 6 months or plans for orthopedic surgery during the study period, chronic uncontrolled pulmonary conditions such as uncontrolled asthma (symptoms > 2 days/week) or dyspnea requiring oxygen, symptomatic peripheral vascular disease, or any other comorbidity that would interfere with the ability to complete and comply with the protocol in the opinion of the investigator
  7. Need for daily anticoagulation use
  8. Allergy to local anesthetic
  9. Locally recurrent or metastatic breast cancer a. History of prior treated malignancies, other than breast cancer, that are now stable, are in remission, and do not require active therapy, are acceptable.

Relevance to patient case: not relevant
Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: Effect of Dexmedetomidine on Emergence Agitation and Postoperative Behavior Changes in Children

Summary: Emergence agitation (EA) is a dissociated state of consciousness in which the child is inconsolable, irritable, uncooperative, typically thrashing, crying, moaning, or incoherent. Although usually transient, it is not only an extremely distressing event for children, parents, and staff, but may also result in self-injury or the need for restraint. The prevalence in children appears to be between 10% and 80% depending upon the definition and measurement tools used and is more frequently observed in the pre-school age-group. A clear correlation has been found between EA and negative postoperative behavioral changes, including anxiety, eating and sleeping disorders, enuresis, fear of darkness, that may persist for an extended period of time affecting emotional and cognitive development.Currently, numerous interventions have been studied to manage EA after surgery. Among them, dexmedetomidine (DEX) as a kind of highly selective α2 adrenergic receptor agonist has been done to reduce EA in children. Unfortunately, no studies examined posthospitalization negative behaviour changes.

Detailed description: The high incidence of EA and postoperative behavioural changes has encouraged paediatric anaesthetists and researchers to study methods to improve the perioperative care of children. Dexmedetomidine is a selective alpha-2 receptor agonist with properties that make it attractive to pediatric use. It provides sedation and anxiolysis acting on these receptors in the locus ceruleus of the pons. It also exerts dose-dependent moderate primary analgesic effects through activation of alpha-2 adrenoreceptors in the dorsal spinal horn causing a subsequent decrease in substance P release. The study aims to explore whether a single low-dose dexmedetomidine in the perioperative period has a preventive effect on EA in children, and through short-term and long-term follow-up, to investigate the effect on post-hospitalization behavioural changes.

Eligibility: Inclusion Criteria:
  1. Age between 2-7 years old
  2. American Society of Anesthesiologists（ASA） score of I or II
  3. Selective ear, nose, and throat surgery under general anaesthesia with sevoflurane
  Exclusion Criteria:
  1. Emergency surgery
  2. were intubated before induction of anaesthesia or not planned for extubation after anaesthesia
  3. had critical illness with haemodynamic instability, active bleeding, cancer, cardiac diseases including arrhythmias, malignant hyperthermia
  4. intellectual disability, or neurological illness with agitation-like symptoms
  5. weighed more than 50 kg
  6. were allergic to dexmedetomidine
  7. The use of sedative or analgesic medications before surgery

Relevance to patient case: not relevant
Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: Study to Assess the Efficacy and Safety of Ryanodex as Adjuvant Treatment in Subjects With EHS

Summary: A double-blind, parallel study of Ryanodex for the adjuvant treatment of exertional heat stroke (EHS) compared to current Standard of Care (SOC) for EHS.

Detailed description: Following triage and primary assessment in the emergency medical facility, subjects will be randomized to 1 of 2 treatment arms, SOC plus Ryanodex or SOC only. Subjects will be dosed and followed for up to 6 hours post-randomization. Current SOC is limited to body cooling and supportive measures.

Eligibility: Inclusion Criteria: Core body temperature of greater than or equal to 40.0 degrees C (104 degrees F); recent history of exertional activity; GCS score less than 13; tachycardia -
  Exclusion Criteria: clinical severe infection; hyperthermia secondary to another condition; endotracheal intubation;; sedative drugs administered prior to or at time of study entry; likelihood of head trauma within 6 months pre-study; positive pregnancy test; history of myocardial infection within 30 days; history of seizure disorder or epilepsy; concomitant or prior use of calcium channel blockers.
  -

Relevance to patient case: not relevant
Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: Differential EBI2 Expression Upon Allelic Status of the rs9557195 Polymorphism

Summary: EBI2 is a risk gene for inflammatory bowel diseases (rs9557195). Patients of the Swiss IBD cohort study have been genotyped for the allelic status of EBI2. The investigators will test the influence of rs9557195 genoty (TT or CC allel), inflammatory activity and current treatment (infliximab vs. vedolizumab) on expression and activity of EBI2 on blood lymphocytes, mRNA expression of EBI2 and UBAC2 (located on the opposite DNA strand of EBI2) and activity of lymphocytes on a migraton assay.

Detailed description: EBI2 is a risk gene for inflammatory bowel diseases (rs9557195). EBI2 is a G protein coupled receptors expressed on the immune cells. EBI2 directs migration and activity of immune cells.
  Patients of the Swiss IBD cohort study have been genotyped for the allelic status of EBI2. The investigators will recruit patients with Crohn's disease and ulcerative colitis, assess epidemiological and clinical parameters (including clinical activity of IBD) draw blood, isolate lymphocytes, DNA and RNA.
  The investigators will test the influence of rs9557195 genotype (TT or CC allel), inflammatory activity and current treatment (infliximab vs. vedolizumab) on expression and activity of EBI2 on blood lymphocytes (by FACS using an EBI2-antibody), mRNA expression (by qPCR) of EBI2 and UBAC2 (located on the opposite DNA strand of EBI2) and activity of lymphocytes on a migration assay.

Eligibility: Inclusion Criteria:
  -  Patient with IBD OR healthy volunteer
  -  No major uncontrolled medical/ surgical/ psychiatric condition requiring ongoing management besides IBD in the respective study groups. Well controlled conditions (i.e. medically controlled arterial hypertension, occupational asthma) may be present
  Exclusion Criteria: none

Relevance to patient case: not relevant