Chronic intermittent intravenous immunoglobulin in heart transplant recipients with elevated donor-specific antibody levels.

Donor-specific antibodies (DSA) are associated with antibody-mediated rejection (AMR) and poor patient survival. In heart transplant, the efficacy of intermittent intravenous immunoglobulin (IVIg) in reducing de novo DSA levels and treating AMR has not been characterized. We retrospectively studied a cohort of 19 patients receiving intermittent IVIg for elevated DSA and examined changes in DSA levels and graft function. Intermittent IVIg infusions were generally safe and well tolerated. Overall, 23 of 62 total DSA (37%) were undetectable after treatment, 21 DSA (34%) had MFI decrease by more than 25%, and 18 (29%) had MFI decrease by less than 25% or increase. The average change in MFI was -51% ± 71% (P < .001). Despite reductions in DSA, among the six patients (32%) with biopsy-confirmed AMR, left ventricular ejection fraction (LVEF) decreased in five (83%) and cardiac index (CI) decreased in three (50%). Conversely, LVEF increased in 91% and CI increased in 70% of biopsy-negative patients. All six AMR patients were readmitted during treatment, four for confirmed or suspected rejection. IVIg infusions may stabilize the allograft in patients with elevated DSA and negative biopsies, but once AMR has developed does not appear to improve allograft function despite decreasing DSA levels.

An Analysis of 5 Years of Randomized Trials in Gastroenterology and Hepatology Reveals 52 Medical Reversals.

BACKGROUND AND AIMS: One manifestation of low-value medical practice is the medical reversal, a practice in widespread use that, once subjected to a randomized controlled trial (RCT), is found to be no better-or worse-than a prior established standard of care. We aimed to determine the prevalence of medical reversals in gastroenterology (GI) journals and characterize these reversals. METHODS: We searched the American Journal of Gastroenterology, Clinical Gastroenterology and Hepatology, Gastroenterology, Gut, Hepatology, and the Journal of Hepatology, reviewing studies published in 2015-2019. We identified RCTs that tested an established clinical practice and produced negative results, considered tentative reversals. Any systematic review or meta-analysis that included the article was categorized as confirming the reversal, refuting the reversal, or providing insufficient data. RESULTS: During the 5-year period, we identified 5,898 original articles, of which 212 tested an established practice and 52 were categorized as unrefuted medical reversals (25% of articles testing standard of care). Of the reversals, 21 (40%) tested procedures and devices, 15 (29%) tested medications, and 8 (15%) tested vitamins/supplements/diet. Twenty-three (44%) considered the alimentary tract, 12 (23%) considered the liver, pancreas, or biliary tract, and 17 (33%) considered endoscopy. Thirty-eight (73%) were funded exclusively by non-industry sources. CONCLUSION: This review reveals a total of 52 reversals across all subfields of GI and medical, procedural, screening, and diagnostic interventions, occurring in 25% of randomized trials testing an established practice. More research is needed to determine the optimal way to engage stakeholders and remove reversed practices from medical care.

Developmental Regulation of Effector and Resident Memory T Cell Generation during Pediatric Viral Respiratory Tract Infection.

Viral respiratory tract infections (VRTI) remain a leading cause of morbidity and mortality among infants and young children. In mice, optimal protection to VRTI is mediated by recruitment of effector T cells to the lungs and respiratory tract, and subsequent establishment of tissue resident memory T cells (Trm), which provide long-term protection. These critical processes of T cell recruitment to the respiratory tract, their role in disease pathogenesis, and establishment of local protective immunity remain undefined in pediatric VRTI. In this study, we investigated T cell responses in the upper respiratory tract (URT) and lower respiratory tract (LRT) of infants and young children with VRTI, revealing developmental regulation of T cell differentiation and Trm generation in situ. We show a direct concurrence between T cell responses in the URT and LRT, including a preponderance of effector CD8+ T cells that was associated with disease severity. During infant VRTI, there was an accumulation of terminally differentiated effector cells (effector memory RA+ T cells) in the URT and LRT with reduced Trm in the early neonatal period, and decreased effector memory RA+ T cell and increased Trm formation with age during the early years of childhood. Moreover, human infant T cells exhibit increased expression of the transcription factor T-bet compared with adult T cells, suggesting a mechanism for preferential generation of effector over Trm. The developmental regulation of respiratory T cell responses as revealed in the present study is important for diagnosing, monitoring, and treating VRTI in the critical early life stages.

Direct-to-Consumer Telemedicine.

The telemedicine industry and adoption of services have grown exponentially in the last 5 years, and the market is expected to reach more than $130 billion by 2025. Most US health institutions and hospital systems are currently using some form of telehealth, and more than 90% of health care executives surveyed across the United States have virtual care on their roadmap for growth. Telemedicine has been proposed as a way to expand the reach of allergy services and allow more patients to manage their disease with an allergy specialist. Technology can help address fragmentation of allergy care, which is currently provided in multiple clinical settings beyond the allergist's office including in primary care, pulmonary, dermatology, ear, nose, and throat, urgent care, and the emergency room. Remote monitoring, specialist second opinions, and synchronous and asynchronous encounters offer opportunities to streamline routine care, especially as smart hardware such as digital inhalers hit the market and reimbursement for telehealth services evolve. To date, allergy care has been a significant area of interest for direct-to-consumer telemedicine solutions, although the care has mainly been offered by nonallergists. Quality assurance and adherence to evidence-based standards, particularly in the self-pay direct-to-consumer space, warrant attention.