A national retrospective cohort study comparing of cefepime versus piperacillin-tazobactam on the development of severe acute kidney injury in patients with septic shock.

Background: Cefepime and piperacillin-tazobactam are commonly used broad-spectrum antibiotics used to treat patients with potential gram-negative bacterial sepsis. Piperacillin-tazobactam has been shown to be associated with acute kidney injury (AKI). However, it has not been compared to cefepime in patients with septic shock.

Medical school ranking and provider outpatient Medicare Part D claims for antibiotics among older patients in the USA.

Background: Our study aimed to assess whether there was a relationship between graduating from higher-ranked medical schools and the rate of prescribing antibiotics among Medicare Part D providers in the USA.

Methods: The study obtained data from the Medicare Part D Prescribers (FY2013-2021) and the Doctor and Clinicians National repositories. A regression model was fitted to assess the relationship between provider medical school ranking and the rate of antibiotic days supplied per 100 beneficiaries at the provider level.

Moral Injury and Healing After the Great War: What G.A. Studdert Kennedy's Experience of Moral Injury Can Teach Us.

In this article, I chart the development of moral injury in the life of Rev. G.A.

Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics.

Purpose: This study investigates a real-world multicenter cohort of patients with urinary tract cancer (UTC), with primary disease sites including the bladder, urethra, and upper tract, who enrolled for research molecular testing of their germline and tumor. The purpose of this study was to evaluate factors that could affect the likelihood of identifying a clinically actionable germline pathogenic variant (PV).

Methods: Patients with UTC were identified from 10 cancer institutes of the Oncology Research Information Exchange Network consortium.

Zinc-alpha-2-glycoprotein Secreted by Triple-Negative Breast Cancer Promotes Peritumoral Fibrosis.

Unlabelled: Obesity is a modifiable predisposition factor for postmenopausal breast cancer. This suggests a localized, reciprocal interaction between breast cancer cells and the surrounding mammary white adipose tissue. To investigate how breast cancer cells alter the composition and function of adipose tissue, we screened the secretomes of 10 human breast cancer cell lines for the ability to modulate the differentiation of adipocyte stem and progenitor cells.

Challenges Facing Antimicrobial Stewardship Programs in the Endemic Region for Coccidioidomycosis.

Coccidioidomycosis poses a significant cost and morbidity burden in the United States. Additionally, coccidioidomycosis requires constant decision-making related to prevention, diagnosis, and management. Delays in diagnosis lead to significant consequences, including unnecessary diagnostic workup and antibacterial therapy.

Apilimod dimesylate in C9orf72 amyotrophic lateral sclerosis: a randomized phase 2a clinical trial.

Apilimod dimesylate is a first-in-class phosphoinositide kinase, FYVE-type zinc finger-containing (PIKfyve) inhibitor with a favourable clinical safety profile and has demonstrated activity in preclinical C9orf72 and TDP-43 amyotrophic lateral sclerosis (ALS) models. In this ALS clinical trial, the safety, tolerability, CNS penetrance and modulation of pharmacodynamic target engagement biomarkers were evaluated. This phase 2a, randomized, double-blind, placebo-controlled, biomarker-end-point clinical trial was conducted in four US centres (ClinicalTrials.

Zinc Alpha-2-Glycoprotein (ZAG/AZGP1) secreted by triple-negative breast cancer promotes tumor microenvironment fibrosis.

Obesity is a predisposition factor for breast cancer, suggesting a localized, reciprocal interaction between breast cancer cells and the surrounding mammary white adipose tissue. To investigate how breast cancer cells alter the composition and function of adipose tissue, we screened the secretomes of ten human breast cancer cell lines for the ability to modulate the differentiation of adipocyte stem and progenitor cells (ASPC). The screen identified a key adipogenic modulator, Zinc Alpha-2-Glycoprotein (ZAG/AZGP1), secreted by triple-negative breast cancer (TNBC) cells.

Hypermedia-based software architecture enables Test-Driven Development.

Objectives: Using agile software development practices, develop and evaluate an architecture and implementation for reliable and user-friendly self-service management of bioinformatic data stored in the cloud.

Materials And Methods: Comprehensive Oncology Research Environment (CORE) Browser is a new open-source web application for cancer researchers to manage sequencing data organized in a flexible format in Amazon Simple Storage Service (S3) buckets. It has a microservices- and hypermedia-based architecture, which we integrated with Test-Driven Development (TDD), the iterative writing of computable specifications for how software should work prior to development.

Trends of Azole Antifungal Prescription in the United States: Medicare Part D Provider Utilization and Payment Data Analysis.

Background: Invasive fungal infections carry a substantial risk of mortality and morbidity. Azole antifungals are used in the treatment of such infections; however, their extensive use can lead to the emergence of antifungal resistance and increased costs to patients and healthcare systems. The aim of this study is to evaluate trends in these antifungals use and costs.

Risk for primary cephalosporin resistance in Gram-negative bacteremia.

Objective: This study aimed to examine the clinical risk factors for cephalosporin resistance in patients with Gram-negative bacteremia caused by (EC), (KP), (ENC), and (PS).

Methods: This retrospective cohort study included 400 adults with Gram-negative bacteremia. The goal was to review 100 cases involving each species and approximately half resistant and half susceptible to first-line cephalosporins, ceftriaxone (EC or KP), or cefepime (ENC or PS).

Response to high dose ipilimumab plus temozolomide after progression on standard or low dose ipilimumab in advanced melanoma: a retrospective analysis.

Background: Despite advancements in checkpoint inhibitor-based immunotherapy, patients with advanced melanoma who have progressed on standard dose ipilimumab (Ipi) + nivolumab continue to have poor prognosis. Several studies support a dose-response activity of Ipi, and one promising combination is Ipi 10mg/kg (Ipi10) + temozolomide (TMZ).

Methods: We performed a retrospective cohort analysis of patients with advanced melanoma treated with Ipi10+TMZ in the immunotherapy refractory/resistant setting (n = 6), using similar patients treated with Ipi3+TMZ (n = 6) as comparison.

Accelerated Infliximab Infusion Safety and Tolerability Is Non-inferior to Standard Infusion Protocol in Inflammatory Bowel Disease Patients: A Randomized Controlled Study.

Background And Aim: Infliximab is typically given over an infusion time of 2 hours, leading to a significant burden in inflammatory bowel disease (IBD) patients. We aimed to determine the safety and cost-effectiveness of an accelerated infliximab infusion of 1 hour, compared with the standard 2-hour infusion.

Methods: Open-label randomized trial where IBD patients receiving maintenance infliximab infusions were randomly assigned to 1- and 2-hour infusion groups, corresponding to study and control groups, respectively.

Performance of Bayesian Area Under the Concentration-Time Curve-Based Pharmacokinetic Dosing Based on a One-Compartment Model and Trough-Only Monitoring for Vancomycin.

A novel Bayesian method was developed to interpret serum vancomycin concentrations (SVCs) following the administration of one or more vancomycin doses with potential varying doses and intervals based on superposition principles. The method was evaluated using retrospective data from 442 subjects from three hospitals. The patients were required to receive vancomycin for more than 3 days, have stable renal function (fluctuation in serum creatinine of ≤0.

Medication dosing in adult patients with reduced lean body mass and kidney injury: A focus on cystatin C.

Purpose: Creatinine-based estimates of glomerular filtration rate (GFR) have been the standard for classifying kidney function and guiding drug dosing for over 5 decades. There have been many efforts to compare and improve different methods to estimate GFR. The National Kidney Foundation recently updated the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without race for creatinine (CKD-EPIcr_R) and creatinine and cystatin C (CKD-EPIcr-cys_R), and the 2012 CKD-EPI equation based on cystatin C (CKD-EPIcys) remains.

Differences in the gut microbiome by physical activity and BMI among colorectal cancer patients.

Associations of energy balance components, including physical activity and obesity, with colorectal cancer risk and mortality are well established. However, the gut microbiome has not been investigated as underlying mechanism. We investigated associations of physical activity, BMI, and combinations of physical activity/BMI with gut microbiome diversity and differential abundances among colorectal cancer patients.

Replicative Instability Drives Cancer Progression.

In the past decade, defective DNA repair has been increasingly linked with cancer progression. Human tumors with markers of defective DNA repair and increased replication stress exhibit genomic instability and poor survival rates across tumor types. Seminal studies have demonstrated that genomic instability develops following inactivation of BRCA1, BRCA2, or BRCA-related genes.

The relationship of vancomycin 24-hour AUC and trough concentration.

Purpose: Prior to the 2020 release of a joint consensus guideline on monitoring of vancomycin therapy for serious methicillin-resistant Staphylococcus aureus (MRSA) infections, clinicians had escalated vancomycin doses for 2 decades while targeting trough concentrations of 15 to 20 µg/mL, leading to an increased frequency of nephrotoxicity. For MRSA infections, the 2020 guideline recommends adjusting doses to achieve a 24-hour area under the concentration-time curve (AUC) of 400 to 600 µg · h/mL; however, monitoring of trough concentrations has been entrenched for 3 decades. Calculating dose regimens based on AUC will require obtaining an increased number of vancomycin serum concentrations and, possibly, advanced software.