Molecular Characterization of NRXN1 Deletions from 19,263 Clinical Microarray Cases Identifies Exons Important for Neurodevelopmental Disease Expression

PURPOSE: The purpose of the current study was to assess the penetrance of NRXN1 deletions. METHODS: We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions. RESULTS: We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P \u3c 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3\u27 end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5\u27 NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035). CONCLUSIONS: The results support the importance of exons near the 5\u27 end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes.Genet Med 19 1, 53-61

Perioperative bleeding management in pediatric patients

PURPOSE OF REVIEW Managing the bleeding pediatric patient perioperatively can be extremely challenging. The primary goals include avoiding hypotension, maintaining adequate tissue perfusion and oxygenation, and maintaining hemostasis. Traditional bleeding management has consisted of transfusion of autologous blood products, however, there is strong evidence that transfusion-related side-effects are associated with increased morbidity and mortality in children. Especially concerning is the increased reported incidence of noninfectious adverse events such as transfusion-related acute lung injury, transfusion-related circulatory overload and transfusion-related immunomodulation. The current approach in perioperative bleeding management of the pediatric patient should focus on the diagnosis and treatment of anemia and coagulopathy with the transfusion of blood products only when clinically indicated and guided by goal-directed strategies. RECENT FINDINGS Current guidelines recommend that a comprehensive multimodal patient blood management strategy is critical in optimizing patient care, avoiding unnecessary transfusion of blood and blood product and limiting transfusion-related side-effects. SUMMARY This article will highlight current guidelines in perioperative bleeding management for our most vulnerable pediatric patients with emphasis on individualized targeted intervention using point-of-care testing and specific coagulation products

Bleeding management for pediatric craniotomies and craniofacial surgery

Pediatric patients when undergoing craniotomies and craniofacial surgery may potentially have significant blood loss. The amount and extent will be dictated by the nature of the surgical procedure, the proximity to major blood vessels, and the age, and weight of the patient. The goals should be to maintain hemodynamic stability and oxygen carrying capacity and to prevent and treat hyperfibrinolysis and dilutional coagulopathy. Over transfusion and transfusion-related side effects should be minimized. This article will highlight the pertinent considerations for managing massive blood loss in pediatric patients undergoing craniotomies and craniofacial surgery. North American and European guidelines for intraoperative administration of fluid and blood products will be discussed

Implementation of an Enhanced Recovery after Surgery Pathway for Transgender and Gender-Diverse Individuals Undergoing Chest Reconstruction Surgery: An Observational Cohort Study

Enhanced Recovery After Surgery (ERAS) protocols are associated with improved clinical outcomes in cisgender breast surgery patients. However, a paucity of research exists regarding transgender and gender-diverse individuals (TGD) in the ERAS framework. The primary objective of this observational cohort study is to describe the implementation of a gender-affirming ERAS protocol and its relationship to hospital length of stay (LOS) in TGD patients following chest reconstruction surgery. The secondary aim is to identify intraoperative predictors of LOS and define variables associated with adverse outcomes. We identified 362 patients in three epochs: a traditional group (n = 144), a partial ERAS implementation group (n = 92), and an ERAS group (n = 126). Exploratory multivariable median regression modeling was performed to identify independent predictors of LOS. We report that the traditional group’s median hospital LOS was 1.1 days compared to 0.3 days in the ERAS group. Intraoperative tranexamic acid administration was associated with significantly shorter LOS (p p p = 0.047). Our data suggest that implementing a multimodal ERAS gender-affirming pathway was associated with improved patient-centered surgical outcomes such as decreased return to the operating room for hematoma evacuation, higher rates of discharge home, and reduced postoperative drainage output