Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

Background: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear.

Methods: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline.

Optimization of Vancomycin Initial Dosing Regimen in Neonates Using an Externally Evaluated Population Pharmacokinetic Model.

Background: Vancomycin therapeutic monitoring guidelines were revised in March 2020, and a population pharmacokinetics-guided Bayesian approach to estimate the 24-hour area under the concentration-time curve to the minimum inhibitory concentration ratio has since been recommended instead of trough concentrations. To comply with these latest guidelines, we evaluated published population pharmacokinetic models of vancomycin using an external dataset of neonatal patients and selected the most predictive model to develop a new initial dosing regimen.

Methods: The models were identified from the literature and tested using a retrospective dataset of Canadian neonates.

Racial Disparities in Medication Use During Pregnancy: Results from the NISAMI Cohort.

Purpose: This study aimed to evaluate racial disparities in medication use and associated factors among pregnant women receiving prenatal care at Brazilian Unified Health System primary care health units in the northeast region.

Patients And Methods: A total of 1058 pregnant women in the NISAMI Cohort were interviewed between June 2012 and February 2014. Medicines used during pregnancy were classified according to the Anatomical Therapeutic Chemical (ATC) classification system and ANVISA pregnancy risk categories.

Immunotherapeutic targeting of surfaceome heterogeneity in AML.

Immunotherapy remains underexploited in acute myeloid leukemia (AML) compared to other hematological malignancies. Currently, gemtuzumab ozogamicin is the only therapeutic antibody approved for this disease. Here, to identify potential targets for immunotherapeutic intervention, we analyze the surface proteome of 100 genetically diverse primary human AML specimens for the identification of cell surface proteins and conduct single-cell transcriptome analyses on a subset of these specimens to assess antigen expression at the sub-population level.

Outcomes of treatment of patella fractures in children and adolescents.

Purpose: The purpose of this study is to assess clinical and functional outcomes in separate cohorts of operatively and nonoperatively managed pediatric patella fractures.

Methods: A retrospective review was completed for patients aged 5-19 years treated for a unilateral patella fracture at a single pediatric level-1 trauma center. Patients were excluded for osteochondral fracture associated with patellar dislocation, polytrauma presentation with additional fractures, or <3 months of clinical follow-up.

Local delivery of accutox synergises with immune-checkpoint inhibitors at disrupting tumor growth.

Background: The Accum platform was initially designed to accumulate biomedicines in target cells by inducing endosomal-to-cytosol escape. Interestingly however, the use of unconjugated Accum was observed to trigger cell death in a variety of cancer cell lines; a property further exploited in the development of Accum-based anti-cancer therapies. Despite the impressive pro-killing abilities of the parent molecule, some cancer cell lines exhibited resistance.

A modified position for optimized skeletal maturity assessment of AIS patients and its impact on 3D spinal and pelvic parameters.

Purpose: A hands-on-wall (HOW) position for low-dose stereoradiography of adolescent idiopathic scoliosis (AIS) patients would allow for skeletal maturity assessment of the hand and wrist. Our aims were twofold: confirm the reliability and validity of skeletal maturity assessment using the HOW radiographs and compare the spinal and pelvic 3D parameters to those of standard hands-on-cheeks (HOC) stereoradiographs.

Methods: Seventy AIS patients underwent two successive stereoradiographs and a standard hand and wrist radiograph on the same day.

Atypical Presentation and Evolution of Necrotizing Enterocolitis as a PIK3CA Pathological Variant.

Activating mutation of PIK3CA is linked with cases of overgrowth syndromes and belongs to the PIK3CA-related overgrowth spectrum (PROS). Mutations in this gene are associated with vascular malformations, brain abnormalities, and an increased risk for certain tumors. We report the case of a newborn girl, preterm at 34 weeks of gestation, referred to our center for atypical necrotizing enterocolitis (NEC).

Distinct personality profiles associated with disease risk and diagnostic status in eating disorders.

Background: Personality traits have been associated with eating disorders (EDs) and comorbidities. However, it is unclear which personality profiles are premorbid risk rather than diagnostic markers.

Methods: We explored associations between personality and ED-related mental health symptoms using canonical correlation analyses.

Feasibility, acceptability, and safety of a novel device for self-collecting capillary blood samples in clinical trials in the context of the pandemic and beyond.

Background: Home blood self-collection devices can enable remote monitoring, but their implementation requires validation. Our objectives were to explore (i) the impact of sampling sites and topical analgesia on capillary blood volume and pain perception and (ii) the safety, acceptability, and failure of capillary self-collection among adults and children using the Tasso-SST device.

Methods: We conducted a two-phase study.

Heterologous HSPC Transplantation Rescues Neuroinflammation and Ameliorates Peripheral Manifestations in the Mouse Model of Lysosomal Transmembrane Enzyme Deficiency, MPS IIIC.

Mucopolysaccharidosis III type C (MPS IIIC) is an untreatable neuropathic lysosomal storage disease caused by a genetic deficiency of the lysosomal N-acetyltransferase, HGSNAT, catalyzing a transmembrane acetylation of heparan sulfate. HGSNAT is a transmembrane enzyme incapable of free diffusion between the cells or their cross-correction, which limits development of therapies based on enzyme replacement and gene correction. Since our previous work identified neuroinflammation as a hallmark of the CNS pathology in MPS IIIC, we tested whether it can be corrected by replacement of activated brain microglia with neuroprotective macrophages/microglia derived from a heterologous HSPC transplant.

ZO-1 interacts with YB-1 in endothelial cells to regulate stress granule formation during angiogenesis.

Zonula occludens-1 (ZO-1) is involved in the regulation of cell-cell junctions between endothelial cells (ECs). Here we identify the ZO-1 protein interactome and uncover ZO-1 interactions with RNA-binding proteins that are part of stress granules (SGs). Downregulation of ZO-1 increased SG formation in response to stress and protected ECs from cellular insults.

Structure and mechanism of lysosome transmembrane acetylation by HGSNAT.

Lysosomal transmembrane acetylation of heparan sulfates (HS) is catalyzed by HS acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT), whose dysfunction leads to lysosomal storage diseases. The mechanism by which HGSNAT, the sole non-hydrolase enzyme in HS degradation, brings cytosolic acetyl-coenzyme A (Ac-CoA) and lysosomal HS together for N-acyltransferase reactions remains unclear. Here, we present cryogenic-electron microscopy structures of HGSNAT alone, complexed with Ac-CoA and with acetylated products.

Environmental Factors Associated With Risk of Crohn's Disease Development in the Crohn's and Colitis Canada - Genetic, Environmental, Microbial Project.

Background & Aims: To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers.

Methods: We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project.

Therapeutic Inducers of Natural Killer cell Killing (ThINKK): preclinical assessment of safety and efficacy in allogeneic hematopoietic stem cell transplant settings.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) remains the standard of care for chemotherapy-refractory leukemia patients, but cure rates are still dismal. To prevent leukemia relapse following HSCT, we aim to improve the early graft-versus-leukemia effect mediated by natural killer (NK) cells. Our approach is based on the adoptive transfer of Therapeutic Inducers of Natural Killer cell Killing (ThINKK).

Unraveling robust brain-behavior links of depressive complaints through granular network models for understanding heterogeneity.

Background: Depressive symptoms are highly prevalent, present in heterogeneous symptom patterns, and share diverse neurobiological underpinnings. Understanding the links between psychopathological symptoms and biological factors is critical in elucidating its etiology and persistence. We aimed to evaluate the utility of using symptom-brain network models to parse the heterogeneity of depressive complaints in a large adolescent sample.

Copy-number variants and polygenic risk for intelligence confer risk for autism spectrum disorder irrespective of their effects on cognitive ability.

Introduction: Rare copy number variants (CNVs) and polygenic risk for intelligence (PRS-IQ) both confer susceptibility for autism spectrum disorder (ASD) but have opposing effects on cognitive ability. The field has struggled to disentangle the effects of these two classes of genomic variants on cognitive ability from their effects on ASD susceptibility, in part because previous studies did not include controls with cognitive measures. We aim to investigate the impact of these genomic variants on ASD risk while adjusting for their known effects on cognitive ability.

Intraoperative changes in large-scale thalamic circuitry following laser ablation of hypothalamic hamartomas.

Background And Objectives: Gelastic seizures due to hypothalamic hamartomas (HH) are challenging to treat, in part due to an incomplete understanding of seizure propagation pathways. Although magnetic resonance imaging-guided laser interstitial thermal therapy (MRgLITT) is a promising intervention to disconnect HH from ictal propagation networks, the optimal site of ablation to achieve seizure freedom is not known. In this study, we investigated intraoperative post-ablation changes in resting-state functional connectivity to identify large-scale networks associated with successful disconnection of HH.

Skin-centered strategies in food allergy prevention.

While the early introduction of food allergens in the infant diet has been shown to be effective at preventing the development of food allergy (FA), its implementation in real life has been associated with various challenges. Interventions aimed at correcting skin barrier dysfunction have been explored in recent decades as a distinct or complementary mean to prevent allergic sensitization through the skin and subsequent development of FA. Studies assessing the application of emollient from birth have yielded conflicting results, and meta-analyses have demonstrated either no effect or only a slight positive effect on FA prevention.

Survival outcomes in pediatric patients with metastatic Ewing sarcoma who achieve a rapid complete response of pulmonary metastases.

Purpose: Our objectives were to compare overall survival (OS) and pulmonary relapse between patients with metastatic Ewing sarcoma (EWS) at diagnosis who achieve rapid complete response (RCR) and those with residual pulmonary nodules after induction chemotherapy (non-RCR).

Patients And Methods: This retrospective cohort study included children under 20 years with metastatic EWS treated from 2007 to 2020 at 19 institutions in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups.