Delving into the Latest Updates on Hartford Hospital, Inc. with Synapse

Overview

Genome-wide association has identified regions of the genome that mediate risk for psychosis. It is possible that variants in these regions confer risk by altering gene expression. This work has predominantly been conducted in individuals of European descent and has focused narrowly on schizophrenia rather than psychosis as a syndrome. In the present study we investigated alterations in gene expression in African American individuals with a range of psychotic diagnoses to increase understanding of the etiology in an underserved population. We performed RNA-seq in whole bloody to survey the transcriptome in 126 patients with a psychosis-spectrum disorder and 217 healthy controls and applied differential gene expression analyses across the genome while controlling for age, sex, population stratification and batch. We found 18 differentially expressed genes (DEGs), some of the locations of the corresponding genes overlap with previously implicated regions for psychosis, but many of which were novel associations. Enrichment analysis of nominally significant genes (p < 0.05) revealed overrepresentation of biological processes relating to platelet, immune and cellular function, and sensory perception. Weighted gene co-expression network analysis, applied to identify modules of co-expressed genes associated with psychosis, revealed 10 modules, one of which was significantly associated with psychosis. This module was significantly enriched for DEGs, and for platelet function. These results support the potential role of immune function in the etiology of psychosis, identify novel candidate gene expression phenotypes that correspond to both established and new genomic regions, in individuals of African American ancestry.

01 May 2025·International Journal of Antimicrobial Agents

Cefiderocol pharmacokinetics in critically-ill patients receiving extra-corporeal membrane oxygenation (ECMO)

Article

Author: Kuti, Joseph L ; Nicolau, David P ; Gluck, Jason A ; Koenig, Christina ; Abouelhassan, Yasmeen ; Fratoni, Andrew J

OBJECTIVECritical illness and organ support such as extracorporeal membrane oxygenation (ECMO) may influence antimicrobial pharmacokinetics. This study investigated cefiderocol pharmacokinetics in critically-ill patients receiving ECMO to understand if standard dosing achieves optimal exposure.METHODSCefiderocol was prescribed according to approved package insert recommendations based on creatinine clearance (CL). Blood sampling was performed at steady-state. Protein binding was determined by ultrafiltration. Concentrations were fitted using the non-parametric adaptive grid algorithm in Pmetrics for R. The fT > MIC for each patient was assessed at MICs of 4, 8, and 16 mg/L. Total AUC_24h was calculated to evaluate comparative exposure to non-ECMO patients.RESULTSFive patients receiving 1.5 g q8h to 2 g q6h dosing regimens were enrolled. Three patients received venous-arterial and two veno-venous ECMO (mean flow rate of 3.9 [range: 2.7-4.9] L/min). A two-compartment model fitted the data best with mean ± standard deviation estimates for CL, volume of the central compartment (V), K₁₂, and K₂₁ of 2.3 ± 0.5 L/h, 4.8 ± 2.3 L, 5.1 ± 2.8 h^-1, and 3.9 ± 3.3 h^-1, respectively. Mean protein binding was 41% (range: 31%-50%). Prescribed dosing regimens achieved 100% fT > MIC up to 16 mg/L for all patients, with a total steady-state AUC_24h of 2501 (range: 1631-3276) mg/L·h.CONCLUSIONSThese are the first data to describe cefiderocol pharmacokinetics in critically-ill patients undergoing ECMO. The currently labelled dosing recommendations based on creatinine CL in these patients were well tolerated and achieved 100% fT > MIC against susceptible bacteria and AUC exposures similar to values in non-ECMO patients.

01 May 2025·Urogynecology

American Urogynecologic Society Best Practice Statement: Evaluation and Counseling of Patients With Pelvic Organ Prolapse

Author: Carberry, Cassandra L. ; Adam, Rony A. ; Ridgeway, Beri M. ; Tulikangas, Paul K. ; Collins, Sarah A.

AbstractWomen with prolapse should have an examination to quantify the loss of anatomic support and should be evaluated for associated bladder, bowel, and prolapse symptoms as well as associated bother. Treatment options should be tailored to meet the patient’s medical health and personal functional goals. In most cases, women should be informed of the range of treatment options including observation as well as nonsurgical and surgical management.

100 Deals associated with Hartford Hospital, Inc.

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100 Translational Medicine associated with Hartford Hospital, Inc.

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Pipeline

Pipeline Snapshot as of 13 May 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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