No abstract

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.

No abstract

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.

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.