Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses.     

Inter‐serotype reassortment among epizootic haemorrhagic disease viruses in the United States

First described in 1955 in New Jersey, epizootic haemorrhagic disease (EHD) causes a severe clinical disease in wild and domestic ruminants worldwide. Epizootic haemorrhagic disease outbreaks occur in deer populations each year from summer to late autumn. The etiological agent is EHD virus (EHDV) which is a double‐stranded segmented icosahedral RNA virus. EHD virus utilizes point mutations and reassortment strategies to maintain viral fitness during infection. In 2018, EHDV serotype 2 was predominantly detected in deer in Illinois. Whole genome sequencing was conducted for two 2018 EHDV2 isolates (IL41747 and IL42218) and the sequence analyses indicated that IL42218 was a reassortant between different serotypes whereas IL41747 was a genetically stable strain. Our data suggest that multiple strains contribute to outbreaks each year.     

Development of a Simulation-Based Mastery Learning Curriculum for Breaking Bad News

Introduction

Physician communication impacts patient outcomes. However, communication skills, especially around difficult conversations, remain suboptimal, and there is no clear way to determine the validity of entrustment decisions. The aims of this study were to 1) describe the development of a simulation-based mastery learning (SBML) curriculum for breaking bad news (BBN) conversation skills and 2) set a defensible minimum passing standard (MPS) to ensure uniform skill acquisition among learners.

Congenital high airway obstruction syndrome (CHAOS): Natural history,prenatal management strategies,and outcomes at a single comprehensive fetal center

PurposeCongenital high airway obstruction syndrome (CHAOS) is a devastating fetal condition of complete airway discontinuity resulting in significant hydrops and extreme lung hyperplasia. It is universally fatal with survival reported only in the rare spontaneous fistulization or EXIT intervention (Ex Utero Intrapartum Treatment). Even in these cases, mortality remains high, and current investigations are targeting prenatal interventions. This report describes our experience with management and fetal interventions for CHAOS, including laser laryngotomy.MethodsWe retrospectively reviewed all patients diagnosed with CHAOS at a single academic institution between 2006 and 2017.ResultsFifteen patients were identified. Eight had obstruction at the trachea and seven at the larynx. In the laryngeal obstructions, three expired shortly after birth, and one survived after spontaneous fistulization and subsequent EXIT to tracheostomy. The remaining three underwent in-utero treatment with laser laryngotomy. One had preterm premature rupture of membranes (PPROM), delivered 3 days post-operatively, and died. Two underwent EXIT to tracheostomy with one surviving to discharge and is currently 2 years old.ConclusionOur study demonstrates the outcomes of a large series of patients diagnosed with CHAOS. While mortality remains high, options for fetal intervention are being explored to allow alterations in the prenatal natural history and improve postnatal outcomes.Type of StudyRetrospective Treatment Study.Level of EvidenceLevel IV.