Multiomic single cell sequencing identifies stemlike nature of mixed phenotype acute leukemia.

Despite recent work linking mixed phenotype acute leukemia (MPAL) to certain genetic lesions, specific driver mutations remain undefined for a significant proportion of patients and no genetic subtype is predictive of clinical outcomes. Moreover, therapeutic strategy for MPAL remains unclear, and prognosis is overall poor. We performed multiomic single cell profiling of 14 newly diagnosed adult MPAL patients to characterize the inter- and intra-tumoral transcriptional, immunophenotypic, and genetic landscapes of MPAL.

CAR T-cell-mediated delivery of bispecific innate immune cell engagers for neuroblastoma.

Novel chimeric antigen receptor (CAR) T-cell approaches are needed to improve therapeutic efficacy in solid tumors. High-risk neuroblastoma is an aggressive pediatric solid tumor that expresses cell-surface GPC2 and GD2 with a tumor microenvironment infiltrated by CD16a-expressing innate immune cells. Here we engineer T-cells to express a GPC2-directed CAR and simultaneously secrete a bispecific innate immune cell engager (BiCE) targeting both GD2 and CD16a.

Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease.

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.

Methods: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing.

Acute nicotinamide riboside supplementation increases human cerebral NAD levels in vivo.

Purpose: The purpose of this study was to determine the effect of acute nicotinamide riboside (NR) supplementation on cerebral nicotinamide adenine dinucleotide (NAD) levels in the human brain in vivo by means of downfield proton MRS (DF H MRS).

Methods: DF H MRS was performed on 10 healthy volunteers in a 7.0 T MRI scanner with spectrally selective excitation and spatially selective localization to determine cerebral NAD levels on two back-to-back days: once after an overnight fast (baseline) and once 4 h after oral ingestion of nicotinamide riboside (900 mg).

Genetic and phenotypic characterization of Parkinson's disease at the clinic-wide level.

Observational studies in Parkinson's disease (PD) deeply characterize relatively small numbers of participants. The Molecular Integration in Neurological Diagnosis Initiative seeks to characterize molecular and clinical features of every PD patient at the University of Pennsylvania (UPenn). The objectives of this study are to determine the feasibility of genetic characterization in PD and assess clinical features by sex and GBA1/LRRK2 status on a clinic-wide scale.

Lessons Learned from a Citywide Abandoned Housing Experiment.

Problem Research Strategy And Findings: The negative impact of vacant and abandoned housing in city neighborhoods is extreme, affecting health and quality of life, promoting violence, and leading to further abandonment. One approach to addressing abandoned housing is to intervene with low-cost interventions that provide a visual sense of ownership. We tested whether a low-cost remediation of abandoned and vacant houses or a trash cleanup intervention would make a noticeable difference in the levels of nearby disrepair, disorder, and public safety.

The Alopecia Areata Severity and Morbidity Index (ASAMI) Study: Results From a Global Expert Consensus Exercise on Determinants of Alopecia Areata Severity.

Importance: Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact.

Objective: To explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI).

Evidence Review: A total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds.

Incidence of Tether Breakage in Anterior Vertebral Body Tethering.

Background: Thoracic anterior vertebral body tethering (TAVBT) is an emerging treatment for adolescent idiopathic scoliosis. Tether breakage is a known complication of TAVBT with incompletely known incidence. We aim to define the incidence of tether breakage in patients with adolescent idiopathic scoliosis who undergo TAVBT.

Characterization of Amyloidosis in the Gastrointestinal Tract With an Emphasis on Histologically Distinct Interstitial Patterns of Deposition and Misinterpretations.

Amyloidosis can involve the gastrointestinal (GI) tract, and deposition can present with varied histologic patterns that make recognition challenging. This retrospective observational study aimed to characterize the deposition patterns in the GI tract and evaluate key quality metrics, including discrepant cases, to improve recognition and provide insight for accurate diagnosis. Sixty-two patients (195 biopsies) with amyloid involvement of the luminal tract were reviewed.

Pimavanserin for psychosis in Parkinson's disease dementia: Subgroup analysis of the HARMONY Trial.

Introduction: Pimavanserin is FDA-approved to treat Parkinson's disease (PD) psychosis. We analyzed the effect of pimavanserin on psychosis in the PD dementia (PDD) subgroup from the phase 3 HARMONY trial.

Methods: This subgroup analysis included PDD patients enrolled in an international, multicenter, randomized discontinuation study of pimavanserin for dementia-related psychosis.

Dasiglucagon for the Treatment of Congenital Hyperinsulinism: A Randomized Phase 3 Trial in Infants and Children.

Context: Congenital hyperinsulinism (CHI) is characterized by dysregulated insulin secretion causing hypoglycemia and consequent brain damage. Dasiglucagon is a glucagon analogue under investigation to treat CHI.

Objective: To evaluate the efficacy and safety of dasiglucagon delivered via continuous subcutaneous infusion to children with CHI and persistent hypoglycemia as add-on to standard of care (SoC).

ECMO in trauma care: What you need to know.

Over the past 10 years, extracorporeal membrane oxygenation (ECMO) use in trauma patients has increased significantly. This includes adult and pediatric trauma patients and even combat casualties. Most ECMO applications are in a venovenous (VV ECMO) configuration for acute hypoxemic respiratory failure or anatomic injuries that require pneumonectomy or extreme lung rest in a patient with insufficient respiratory reserve.

Association between the presence of an advanced airway and ventilation rate during pediatric CPR: A report from the Videography in Pediatric Resuscitation (VIPER) collaborative.

Objective: To determine the association between presence of an advanced airway during pediatric cardiopulmonary resuscitation (CPR) and ventilation rates.

Methods: Prospective observational study, January 2017 to June 2020. Patients ≤18 years receiving CC for ≥2 minutes were enrolled.

Novel Use of Dasiglucagon, a Soluble Glucagon Analog, for the Treatment of Hyperinsulinemic Hypoglycemia Secondary to Suspected Insulinoma: A Case Report.

Introduction: Hyperinsulinemic hypoglycemia is the most common cause of persistent hypoglycemia in children and adults. In adolescents and adults, hyperinsulinemic hypoglycemia is most frequently caused by an insulin-producing tumor.

Case Presentation: A 17-year-old, previously healthy male presented with recurrent and severe episodes of hypoglycemia.

Whole-Exome sequencing analysis identified TMSB10/TRABD2A locus to be associated with carfilzomib-related cardiotoxicity among patients with multiple myeloma.

Background: Proteasome inhibitor Carfilzomib (CFZ) is effective in treating patients with refractory or relapsed multiple myeloma (MM) but has been associated with cardiovascular adverse events (CVAE) such as hypertension, cardiomyopathy, and heart failure. This study aimed to investigate the contribution of germline genetic variants in protein-coding genes in CFZ-CVAE among MM patients using whole-exome sequencing (WES) analysis.

Methods: Exome-wide single-variant association analysis, gene-based analysis, and rare variant analyses were performed on 603,920 variants in 247 patients with MM who have been treated with CFZ and enrolled in the Oncology Research Information Exchange Network (ORIEN) at the Moffitt Cancer Center.

Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus in Children.

Background And Objectives: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children.

Methods: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort.

Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification.

Mixed phenotype acute leukemia (MPAL) is a leukemia whose biologic drivers are poorly understood, therapeutic strategy remains unclear, and prognosis is poor. We performed multiomic single cell (SC) profiling of 14 newly diagnosed adult MPAL patients to characterize the immunophenotypic, genetic, and transcriptional landscapes of MPAL. We show that neither genetic profile nor transcriptome reliably correlate with specific MPAL immunophenotypes.