The Use of Cyclosporine for Recurrent Hepatitis C After Liver Transplant: A Randomized Pilot Study

Background  

Cyclosporine has antiviral activity in vitro against hepatitis C (HCV). We performed a pilot study to prospectively determine the antiviral effect of cyclosporine during therapy with PEGalfa-2a and ribavirin in liver transplant recipients with recurrent HCV infection.     

A strategy of rapid cardioversion minimizes the significance of early recurrent atrial tachyarrhythmias after ablation for atrial fibrillation

A Strategy of Rapid Cardioversion. Background: The significance of early recurrent atrial tachyarrhythmias after atrial fibrillation (AF) ablation is unclear. Atrial remodeling driven by these tachyarrhythmias can result in electrical, contractile, and structural changes that may impair long‐term therapy success. Aggressive attempts to restore sinus rhythm in the temporal period of healing after ablation might improve outcomes. Methods: A total of 1,759 AF ablations were performed at Intermountain Medical Center or LDS Hospital. A total of 455 of those were among patients requiring repeat ablations. Patients were instructed to take their pulse daily and, if greater than 100 bpm or irregular, present the following business day fasting to the clinic for evaluation and cardioversion if AF or atrial flutter (AFL) were present. Results: Of the ablations performed, a total of 515 (29%, age: 65.6 ± 11.2 years, male: 57.9%) developed AF/AFL that required cardioverison. The majority of these arrhythmias first occurred in the initial 90 days (63.7%) postablation. During this period, 62.8% were on an antiarrhythmic drug (AAD). Only 25.1% were using an AAD at 3 months. The majority of ablations (75.6%) who experienced AF/AFL within the first 90 days after ablation were in sinus rhythm with no AAD at 1 year. Further, 48% of those with the first recurrence from 90 to 180 days were in sinus rhythm with no AAD at 1 year. Conclusions: The time at which the first recurrence of AF/AFL occurs impacts long‐term outcomes. An aggressive strategy of rapid cardioversion postablation reduces the significance of recurrent AF/AFL during the first 6 months . (J Cardiovasc Electrophysiol, Vol. 22, pp. 761‐766, July 2011)     

CADASIL mutations sensitize the brain to ischemia via spreading depolarizations and abnormal extracellular potassium homeostasis

Cerebral autosomal dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL) is the most common monogenic form of small vessel disease characterized by migraine with aura, leukoaraiosis, strokes, and dementia. CADASIL mutations cause cerebrovascular dysfunction in both animal models and humans. Here, we showed that 2 different human CADASIL mutations (Notch3 R90C or R169C) worsen ischemic stroke outcomes in transgenic mice; this was explained by the higher blood flow threshold to maintain tissue viability compared with that in wild type (WT) mice. Both mutants developed larger infarcts and worse neurological deficits compared with WT mice, regardless of age or sex after filament middle cerebral artery occlusion. However, full-field laser speckle flowmetry during distal middle cerebral artery occlusion showed comparable perfusion deficits in mutants and their respective WT controls. Circle of Willis anatomy and pial collateralization also did not differ among the genotypes. In contrast, mutants had a higher cerebral blood flow threshold, below which infarction ensued, suggesting increased sensitivity of brain tissue to ischemia. Electrophysiological recordings revealed a 1.5- to 2-fold higher frequency of peri-infarct spreading depolarizations in CADASIL mutants. Higher extracellular K⁺ elevations during spreading depolarizations in the mutants implicated a defect in extracellular K⁺ clearance. Altogether, these data reveal a mechanism of enhanced vulnerability to ischemic injury linked to abnormal extracellular ion homeostasis and susceptibility to ischemic depolarizations in CADASIL.     

EHR-based cohort assessment for multicenter RCTs: a fast and flexible model for identifying potential study sites

ObjectiveThe Recruitment Innovation Center (RIC), partnering with the Trial Innovation Network and institutions in the National Institutes of Health-sponsored Clinical and Translational Science Awards (CTSA) Program, aimed to develop a service line to retrieve study population estimates from electronic health record (EHR) systems for use in selecting enrollment sites for multicenter clinical trials. Our goal was to create and field-test a low burden, low tech, and high-yield method.Materials and MethodsIn building this service line, the RIC strove to complement, rather than replace, CTSA hubs’ existing cohort assessment tools. For each new EHR cohort request, we work with the investigator to develop a computable phenotype algorithm that targets the desired population. CTSA hubs run the phenotype query and return results using a standardized survey. We provide a comprehensive report to the investigator to assist in study site selection.ResultsFrom 2017 to 2020, the RIC developed and socialized 36 phenotype-dependent cohort requests on behalf of investigators. The average response rate to these requests was 73%.DiscussionAchieving enrollment goals in a multicenter clinical trial requires that researchers identify study sites that will provide sufficient enrollment. The fast and flexible method the RIC has developed, with CTSA feedback, allows hubs to query their EHR using a generalizable, vetted phenotype algorithm to produce reliable counts of potentially eligible study participants.ConclusionThe RIC’s EHR cohort assessment process for evaluating sites for multicenter trials has been shown to be efficient and helpful. The model may be replicated for use by other programs.     

The OneFlorida Data Trust: a centralized,translational research data infrastructure of statewide scope

The OneFlorida Data Trust is a centralized research patient data repository created and managed by the OneFlorida Clinical Research Consortium (“OneFlorida”). It comprises structured electronic health record (EHR), administrative claims, tumor registry, death, and other data on 17.2 million individuals who received healthcare in Florida between January 2012 and the present. Ten healthcare systems in Miami, Orlando, Tampa, Jacksonville, Tallahassee, Gainesville, and rural areas of Florida contribute EHR data, covering the major metropolitan regions in Florida. Deduplication of patients is accomplished via privacy-preserving entity resolution (precision 0.97–0.99, recall 0.75), thereby linking patients’ EHR, claims, and death data. Another unique feature is the establishment of mother-baby relationships via Florida vital statistics data. Research usage has been significant, including major studies launched in the National Patient-Centered Clinical Research Network (“PCORnet”), where OneFlorida is 1 of 9 clinical research networks. The Data Trust’s robust, centralized, statewide data are a valuable and relatively unique research resource.     

Adoptive T-Cell Therapy in Advanced Colorectal Cancer: A Systematic Review

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the US. For the vast majority of patients with advanced CRC (ie, for those in whom metastatic tumors are unresectable), treatment is palliative and typically involves chemotherapy, biologic therapy, and/or immune checkpoint inhibition. In recent years, the use of adoptive T-cell therapy (ACT), leveraging the body’s own immune system to recognize and target cancer, has become increasingly popular. Unfortunately, while ACT has been successful in the treatment of hematological malignancies, it is less efficacious in advanced CRC due in part to a lack of productive immune infiltrate. This systematic review was conducted to summarize the current data for the efficacy and safety of ACT in advanced CRC. We report that ACT is well tolerated in patients with advanced CRC. Favorable survival estimates among patients with advanced CRC receiving ACT demonstrate promise for this novel treatment paradigm. However, additional stage I/II clinical trials are needed to establish the efficacy and safety of ACT in patients with CRC.     

Point-of-Care Cardiac Ultrasound: Feasibility of Performance by Noncardiologists

Cardiac ultrasound has been used for decades to assess a wide variety of structural and functional pathology, as well as to monitor response to therapy. It offers the advantages of noninvasive, real-time dynamic functional assessment without the risk of radiation. Cardiologists have traditionally employed this modality and have established robust guidelines on the use of echocardiography. However, other specialties such as emergency medicine and critical care have realized the benefit of cardiac ultrasound and have established specialty guidelines in its use. There is growing evidence for the benefit of cardiac ultrasound at the point of care on hospital wards, clinics, and even pre-hospital environments as well. The pervasive use of focused ultrasound is perhaps most evident in the advent of ultrasound training in undergraduate medical curricula. This paper reviews some of the key literature on the use of focused, point-of-care ultrasound by noncardiologists. Feasibility, clinical utility, and emerging trends are reviewed.