Enhanced Killing of Methicillin-Resistant Staphylococcus aureus with Ceftaroline or Vancomycin in Combination with Carbapenems.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high rates of treatment failure, even when antibiotics showing in vitro susceptibility are used. Early optimization of therapy is crucial to reduce morbidity and mortality. Building on our previous research on carbapenem therapy for methicillin-susceptible S.

Phenotypic and Genetic Heterogeneity of a Pakistani Cohort of 15 Consanguineous Families Segregating Variants in Leber Congenital Amaurosis-Associated Genes.

Background: Leber congenital amaurosis (LCA) is a congenital onset severe form of inherited retinal dystrophy (IRD) and a common cause of pediatric blindness. Disease-causing variants in at least 14 genes are reported to predispose LCA phenotype. LCA is inherited as an autosomal recessive disease.

Two-year follow-up of gait and postural control following initiation of recombinant human tripeptidyl intracerebroventricular enzyme replacement therapy in two atypical CLN2 patients.

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease.

Rapid and quantitative functional interrogation of human enhancer variant activity in live mice.

Functional analysis of non-coding variants associated with congenital disorders remains challenging due to the lack of efficient in vivo models. Here we introduce dual-enSERT, a robust Cas9-based two-color fluorescent reporter system which enables rapid, quantitative comparison of enhancer allele activities in live mice in less than two weeks. We use this technology to examine and measure the gain- and loss-of-function effects of enhancer variants previously linked to limb polydactyly, autism spectrum disorder, and craniofacial malformation.

Adagrasib in KRYSTAL-12 has Not Broken the KRAS G12C Enigma Code of the Unspoken 6-Month PFS Barrier in NSCLC.

Mutations in KRAS G12C are among the more common oncogenic driver mutations in non-small cell lung cancer (NSCLC). In December 2022, the US Food and Drug Administration (FDA) granted accelerated approval to adagrasib, a small molecule covalent inhibitor of KRAS G12C, for the treatment of patients with locally advanced or metastatic KRAS G12C mutant NSCLC who received at least one prior systemic therapy based on promising results from phase 1 and 2 trials wherein adagrasib demonstrated a median PFS of 6.5 months.

Pancreaticoduodenectomy in trauma patients with grade IV-V duodenal or pancreatic injuries: a post hoc analysis of an EAST multicenter trial.

Introduction: The utility of pancreaticoduodenectomy (PD) for high-grade traumatic injuries remains unclear and data surrounding its use are limited. We hypothesized that PD does not result in improved outcomes when compared with non-PD surgical management of grade IV-V pancreaticoduodenal injuries.

Methods: This is a retrospective, multicenter analysis from 35 level 1 trauma centers from January 2010 to December 2020.

Systematic review of long-acting injectable antipsychotic medications approved from 2008 to october 2024 and agents in phase 3.

Objective: The purpose of this systematic review is to provide a detailed summary of the long-acting injectable antipsychotic medications approved by the Food and Drug Administration (FDA) between 2008 to October 2024. We aim to provide an overview of the mechanism of action, indications for both labeled and off-label uses, evidence for efficacy, dosing, and the adverse effects of each drug.

Methods: Studies published from 2008 to October 1, 2024, were identified from the PubMed database, using the keywords: 'long-acting injectables' OR 'LAI*'AND 'psychopharm*" OR 'schizophrenia' The authors conducted a focused analysis independently and reached a consensus on the recently approved long-acting injectable antipsychotic medications to be included in this systematic review.

Dietary methionine supplementation promotes mice hematopoiesis after irradiation.

Background: With the increasing risk of nuclear exposure, more attention has been paid to the prevention and treatment of acute radiation syndrome (ARS). Although amino acids are key nutrients involved in hematopoietic regulation, the impacts of amino acids on bone marrow hematopoiesis following irradiation and the associated mechanisms have not been fully elucidated. Hence, it is of paramount importance to study the changes in amino acid metabolism after irradiation and their effects on hematopoiesis as well as the related mechanisms.

Real-World Prevalence, Treatment Patterns, and Outcomes for Patients With HER2 (ERBB2)-Mutant Metastatic Non-Small Cell Lung Cancer, From a US-Based Clinico-Genomic Database.

Objectives: Targeted therapies have been shown to improve outcomes in metastatic non-small cell lung cancer (mNSCLC) with driver mutations. We evaluated the real-world prevalence of human epidermal growth factor receptor 2 (HER2; ERBB2) tumor gene mutations among patients with mNSCLC and described historical treatments and outcomes in patients with HER2-mutant mNSCLC, during a period when there was no approved targeted therapy for HER2-mutant mNSCLC.

Materials And Methods: This retrospective observational study used a US nationwide de-identified NSCLC clinico-genomic database.

Qualitative Assessment of Health-Related Quality of Life Impacts Associated with Sickle Cell Disease in the United States and United Kingdom.

Introduction: Individuals living with sickle cell disease (SCD) commonly report impaired health-related quality of life (HRQoL). However, impacts of SCD on HRQoL and the unmet needs of SCD treatment/management are under-researched. This study characterized the impact of SCD on HRQoL and identified the unmet needs of individuals with SCD.

Creating a plasma coordination center to support COVID-19 outpatient trials across a national network of hospital blood banks.

Introduction: In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

Methods: A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

Adagrasib in the Treatment of KRAS p.G12C Positive Advanced NSCLC: Design, Development and Place in Therapy.

One of the most common mutations seen in lung cancers are mutations in Kristen Rat Sarcoma Viral Oncogene Homolog (KRAS), observed in 25-30% of patients with NSCLC. Mutations in KRAS result in oncogenesis via persistent activation of the MAPK/ERK pathways. Although once thought to be "undruggable", KRAS p.

Infectivity and Immunogenicity of Live-Attenuated Respiratory Syncytial Virus Vaccines in Human Immunodeficiency Virus-Exposed Uninfected Children.

Background: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory illness among young children. Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) children experience a higher burden of RSV disease and have immune abnormalities that may influence their responses to live-attenuated RSV vaccines.

Methods: In a pooled analysis of clinical trials of 7 live-attenuated, intranasal RSV vaccines conducted by the IMPAACT Network among children 6 to <25 months of age with serum RSV-neutralizing titers of <1:40, the infectivity and immunogenicity of these vaccines were compared among HEU and HIV-unexposed, uninfected (HUU) children.

Opioid prescriptions following behavioral health training among primary care providers.

Background: Overdose deaths due to opioids are a major concern in the United States. Physicians often report inadequate training in chronic pain and substance use disorder management. Here, we evaluate whether a specialized program, the Train New Trainers Primary Care Psychiatry (TNT PCP) Fellowship, affected opioid prescription practices among primary care physicians.

Dihydroxyacetone phosphate is a novel predictor of hepatic fibrosis in Latino adolescents with obesity.

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common pediatric liver disease and can progress to liver fibrosis. Latino adolescents have increased MASLD and fibrosis risk. While fibrosis is diagnosed by biopsy or imaging, more accessible, noninvasive, and economical screening methods are needed.

Case report: High grade serous fallopian tube carcinoma with rare gene fusion presenting as widespread peritoneal carcinomatosis.

The discovery of gene fusions involving Neuregulin-1 () within solid tumors has important therapeutic implications, as they are being actively explored as targets for emerging ERBB/ERBB2/ERBB3-directed anti-cancer agents. fusions are very uncommon across all tumor types and are infrequently documented in the medical literature. We report a female patient presenting with widespread peritoneal carcinomatosis diagnosed as high grade serous fallopian tube carcinoma, which harbored a previously undescribed :: fusion.

Combined impact of prediabetes and hepatic steatosis on cardiometabolic outcomes in young adults.

Objectives: This study aimed to investigate the impact of hepatic steatosis on cardiometabolic outcomes in young adults with prediabetes.

Methods: A nationwide cohort study was conducted with 896,585 young adults under 40 years old without diabetes or previous history of cardiovascular disease. Hepatic steatosis was identified using a fatty liver index of ≥ 60.

Dimerization of the deaminase domain and locking interactions with Cas9 boost base editing efficiency in ABE8e.

CRISPR-based DNA adenine base editors (ABEs) hold remarkable promises to address human genetic diseases caused by point mutations. ABEs were developed by combining CRISPR-Cas9 with a transfer RNA (tRNA) adenosine deaminase enzyme and through directed evolution, conferring the ability to deaminate DNA. However, the molecular mechanisms driving the efficient DNA deamination in the evolved ABEs remain unresolved.

Correction Rates and Clinical Outcomes in Hospitalized Adults With Severe Hyponatremia: A Systematic Review and Meta-Analysis.

Importance: Hyponatremia treatment guidelines recommend limiting the correction of severe hyponatremia during the first 24 hours to prevent osmotic demyelination syndrome (ODS). Recent evidence suggests that slower rates of correction are associated with increased mortality.

Objective: To evaluate the association of sodium correction rates with mortality among hospitalized adults with severe hyponatremia.