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This approach may not be best for patients with severe AWS in the ICU, as evidenced by the high use of DEX as an adjunctive medication. B Conclusions: b The most common AWS management strategy in our ICU was a symptom-triggered approach. B Introduction: b Alcohol withdrawal syndrome (AWS) is a common, complicating factor affecting the care of hospitalized patients. [Extracted from the article]

B Learning Objectives: b Organ donation awareness is increasing but the donor pool has plateaued despite an ever-growing need. Data were collected from the local organ procurement organization (OPO) and electronic health record, including patient characteristics, family demographics, hospital outcomes, communication, and organ donation authorization. Understanding these associations will guide future studies of modifiable processes surrounding organ donation authorization, and thereby inform best practices to increase the pool of pediatric organ donors. [Extracted from the article]

Objective: To evaluate the accuracy of next-generation sequencing-based quantitative cell-free DNA analysis for fetal antigen genotyping in individuals with alloimmunized pregnancies undergoing clinical testing in practices across the United States as early as 10 weeks of gestation, with the objective of identifying individuals with pregnancies at risk for hemolytic disease of the fetus and newborn and guiding management., Methods: This prospective cohort study included patients with alloimmunized pregnancies undergoing clinical fetal antigen cell-free DNA analysis between 10 0/7 and 37 0/7 weeks of gestation at 120 clinical sites. Both the pregnant person with the alloimmunized pregnancy and the neonates resulting from the pregnancies were included. The laboratory issued the cell-free DNA results prospectively as a part of clinical care. After delivery, neonatal buccal swabs collected between 0 and 270 days of life were sent to an outside independent laboratory for antigen genotyping. The outside laboratory was blinded to the fetal cell-free DNA results, and the results were compared. Concordance was reported for the fetal antigen cell-free DNA analysis for antigens to which the pregnant person was alloimmunized and for all antigens for which the pregnant person was genotype negative., Results: A total of 156 pregnant people who received clinically ordered cell-free DNA fetal antigen testing provided neonatal buccal swabs for genotyping after delivery. Overall, 15.4% of participants were Hispanic, 9.0% were non-Hispanic Black, 65.4% were non-Hispanic White, 4.5% were Asian, 1.3% were more than one race or ethnicity, and 4.5% were unknown. The median gestational age at the time of testing was 16.4 weeks with a median fetal fraction of 11.1%. Concordance between cell-free DNA analysis results and neonatal genotype was determined for 465 antigen calls for the following antigens: K1 (n=143), E (124), C (60), Fy a (50), c (47), and D(RhD) (41). These 465 calls included 145 in which the fetus was antigen positive and 320 in which the fetus was antigen negative. We observed complete concordance between prenatal fetal antigen cell-free DNA analysis results and neonatal genotypes for the 465 calls, resulting in 100% sensitivity, specificity, and accuracy., Conclusion: In a diverse multicenter cohort, cell-free DNA analysis was highly sensitive and specific for determining fetal antigen genotype as early as 10 weeks of gestation in individuals with alloimmunized pregnancies. Taken together with previously published evidence, this study supports the implementation of cell-free DNA testing to manage individuals with alloimmunized pregnancies in the United States., Competing Interests: Financial Disclosure Jennifer Hoskovec, Julia Wynn, and Shannon Rego are employees of BillionToOne, Inc and have options/equity in BillionToOne, Inc. Haley King and Ashley Wilson are paid contractors with BillionToOne, Inc. Kenneth J. Moise is a paid consultant of BillionToOne, Inc. Olaide Ashimi Balogun, Kirsten Emanuel, and Rachael Overcash received research funding from BillionToOne, Inc. Julia Wynn received National Society of Genetic Counselor National Meeting Speaker compensation. Shannon Rego received a stipend from the American College of Medical Genetics and Genomics as part of the Clingen Adult Actionability Working Group. The other authors did not report any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Bullous pemphigoid (BP) is the most common autoimmune blistering disorder of the skin. It is typified by tense blisters with a subepidermal split and mixed dermal inflammatory infiltrate on histology. Biopsy of the perilesional skin for direct immunofluorescence (DIF) has become the gold standard in the diagnosis of BP. Currently there is a pervasive clinical opinion that the lower extremity is a site with a high false-negative rate (FNR) for DIF in the diagnosis of BP. This notion is primarily based on 2 early studies from the 1980s without more recent confirmatory studies. To readdress this question regarding the lower extremities, a retrospective study from 2012 to 2018 was performed in our institution that evaluated the FNR of DIF by an anatomical site in the diagnosis of BP. Cases of BP were identified using standard criteria (clinical and histological data reviewed in cases with negative DIF), and overall, 79 patients were included in the study. A total of 4 false-negative DIF biopsies were verified. Two negative DIF were from the lower extremity yielding a FNR of 10% compared with 4% on the trunk and 3% from the upper extremity, with no statistically significant difference by anatomical sites. Our study fails to demonstrate a high FNR of DIF from the lower extremity in the diagnosis of BP., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified RASA1 mutations in 50% of patients with CM-AVM. Herein we studied non-RASA1 patients to further elucidate the pathogenicity of CMs and AVMs., Methods: We conducted a genome-wide linkage study on a CM-AVM family. Whole-exome sequencing was also performed on 9 unrelated CM-AVM families. We identified a candidate gene and screened it in a large series of patients. The influence of several missense variants on protein function was also studied in vitro., Results: We found evidence for linkage in 2 loci. Whole-exome sequencing data unraveled 4 distinct damaging variants in EPHB4 in 5 families that cosegregated with CM-AVM. Overall, screening of EPHB4 detected 47 distinct mutations in 54 index patients: 27 led to a premature stop codon or splice-site alteration, suggesting loss of function. The other 20 are nonsynonymous variants that result in amino acid substitutions. In vitro expression of several mutations confirmed loss of function of EPHB4. The clinical features included multifocal CMs, telangiectasias, and AVMs., Conclusions: We found EPHB4 mutations in patients with multifocal CMs associated with AVMs. The phenotype, CM-AVM2, mimics RASA1 -related CM-AVM1 and also hereditary hemorrhagic telangiectasia. RASA1 -encoded p120RASGAP is a direct effector of EPHB4. Our data highlight the pathogenetic importance of this interaction and indicts EPHB4-RAS-ERK signaling pathway as a major cause for AVMs., (© 2017 American Heart Association, Inc.)

The proliferation of clandestine methamphetamine laboratories (meth labs) as a result of the growing popularity of the drug has resulted in an increasing incidence of burn injuries associated with laboratory accidents. We undertook this study to characterize these injuries. Fifteen consecutive patients were identified and case-matched by age and TBSA to 45 control subjects. Most meth lab patients were men, Caucasian, unemployed, and positive for polysubstance abuse. Resuscitation requirements were 1.8 times greater in these patients. There was a higher incidence of inhalational injury corresponding to higher intubation and tracheostomy rate and longer ventilator days among meth lab patients. The rate of nosocomial pneumonia, skin graft loss, and mortality were not different between the two groups. Meth lab injury is unique and requires more critical care resources. It also is associated with lack of insurance coverage and poor follow-up after injury. This injury has a significant impact not only on patients but also on the healthcare system.