The Efficacy and Safety of Angiotensin II for Treatment of Vasoplegia in Critically Ill Patients: A Systematic Review.

Objectives: To summarize evidence regarding intravenous angiotensin II administration in critical illness and provide an updated understanding of its effects on various organ dysfunction and renin-angiotensin system (RAS) biomarkers.

Design: A systematic review.

Setting: A search of PubMed, Embase, and the Cochrane Library from inception to May 3, 2024.

School-Based Physical Activity Program Implementation Is Enhanced With Support From Community-Based Partners.

Background: School-based physical activity (PA) programs are an equitable, evidence-based approach to combat health and PA disparities. This study examined factors associated with implementation of BE Physically Active 2Day (BEPA 2.0), a K-5 school-based PA program, and examined how support from Cooperative Extension via Supplemental Nutrition Assistance Program Education (SNAP-Ed) partners influenced implementation.

The potential of antibody-drug conjugates for effective therapy in diffuse large B-cell lymphoma.

Introduction: Antibody-drug conjugates (ADCs) are a rapidly evolving class of anti-cancer drugs with a significant impact on management of hematological malignancies including diffuse large B-cell lymphoma (DLBCL). ADCs combine a cytotoxic drug (a.k.

Proximal Femur Fractures: Evaluating the Necessity of On-Call Surgery.

The decision of the Joint Federal Committee on the treatment of hip fractures stipulates that proximal femur fractures must be treated within the first 24 h. This leads to organizational and personnel difficulties in day-to-day care. Therefore, we investigated the question at what times of day we operate to maintain this timeline and whether there is a difference in the outcome for the patients according to treatment hours.

Efficacy and Safety of a Mixture of Microencapsulated Sodium Butyrate, Probiotics, and Short Chain Fructooligosaccharides in Patients with Irritable Bowel Syndrome-A Randomized, Double-Blind, Placebo-Controlled Study.

Biotics are increasingly being used in the treatment of irritable bowel syndrome (IBS). This study aimed to assess the efficacy and safety of a mixture of microencapsulated sodium butyrate, probiotics ( DSM 26357, DSM 32418, DSM 32946, DSM 32403, and DSM 32269), and short-chain fructooligosaccharides (scFOSs) in IBS patients. This was a randomized, double-blind, placebo-controlled trial involving 120 adult participants with IBS.

Synthesis of Pyrazole-Based Inhibitors of the Bacterial Enzyme -Succinyl-l,l-2,6-Diaminopimelic Acid Desuccinylase (DapE) as Potential Antibiotics.

Based on the inhibitory potencies from earlier reported tetrazole thioether analogs, we now describe the synthesis and inhibition of pyrazole-based inhibitors of -succinyl-l,l-2,6-diaminopimelic acid desuccinylase (DapE) from (DapE). The most potent pyrazole analog bears an aminopyridine amide with an IC of 17.9 ± 8.

Translational and clinical comparison of whole genome and transcriptome to panel sequencing in precision oncology.

Precision oncology offers new cancer treatment options, yet sequencing methods vary in type and scope. In this study, we compared whole-exome/whole-genome (WES/WGS) and transcriptome sequencing (TS) with broad panel sequencing by resequencing the same tumor DNA and RNA as well as normal tissue DNA for germline assessment, from 20 patients with rare or advanced tumors, who were originally sequenced by WES/WGS ± TS within the DKFZ/NCT/DKTK MASTER program from 2015 to 2020. Molecular analyses resulted in a median number of 2.

Binding mode-guided development of high-performance antibodies targeting site-specific posttranslational modifications.

Posttranslational modifications (PTMs) of proteins play critical roles in regulating many cellular events. Antibodies targeting site-specific PTMs are essential tools for detecting and enriching PTMs at sites of interest. However, fundamental difficulties in molecular recognition of both PTM and surrounding peptide sequence have hindered the efficient generation of highly sequence-specific anti-PTM antibodies.

Discovery of Novel Small-Molecule Inhibitors Disrupting the MTDH-SND1 Protein-Protein Interaction.

MTDH-SND1 protein-protein interaction (PPI) plays an important role in the initiation and development of tumors, and it is a target for the treatment of breast cancer. In this study, we identified and synthesized a series of novel small-molecule inhibitors of MTDH-SND1 PPI. The representative compound showed potent activity against MTDH-SND1 PPI with an IC of 487 ± 99 nM and tight binding to the SND1-purified protein with a value of 279 ± 17 nM.

Exploratory disproportionality analysis of potentially drug-induced eosinophilic pneumonia using United States Food and Drug Administration adverse event reporting system.

Drug-induced eosinophilic pneumonia (EP) is an uncommon adverse drug reaction. Many drugs have been reported to cause EP, the evidence mainly being in the form of case reports/case series. This study aims to conduct an exploratory analysis of the United States Food and Drug Administration adverse event reporting system (FAERS) database to identify previously unknown drugs that can cause EP and supplement the available evidence for known culprit drugs.

Quantitative determination of leptin hormone using gold nanoparticle-based lateral flow assay.

A lateral flow assay (LFA) has been developed that can be used in point-of-care (PoC) use for the sensitive determination of leptin hormone. The limit of detection value was 0.158 ng/mL and the limit of quantification value was 0.

The "Outline Sign": Thin Hyperenhancing Perimeter as an MR Imaging Feature of Meningioma. A Useful Tool in the Temporal Bone Region for Differentiating Meningiomas from Schwannomas and Paragangliomas.

Background And Purpose: This study investigates the practicality and utility of the "outline sign," which refers to the thin curvilinear hyperenhancing line that may be seen along the margin of a meningioma on a spin-echo postcontrast T1-weighted image. For cases in which the differential diagnosis may include other tumors, visualization of the outline sign may help to increase the diagnostic confidence for a meningioma. Therefore, in the temporal bone region such as the cerebellopontine angle or jugular foramen, where differential considerations may include a schwannoma or paraganglioma, we additionally investigated whether the outline sign may be observed in these nonmeningioma lesions.

Preparing Surrogates for Decision-Making: Development and Pilot Testing of Prepare for Their Care.

Context: Surrogate decision-makers have expressed the need for better preparation around communication and medical decision-making.

Objectives: This mixed-methods feasibility study aimed to assess the feasibility and usability of an online program to prepare surrogates for their role.

Methods: We developed a 2-part program for surrogates called PREPARE For THEIR Care with a diverse group of Community Advisory Board members and caregivers recruited from the National Patient Advocacy Foundation.

Validation of the inadequate delivery of oxygen index in an adult cardiovascular intensive care unit.

Objective: Machine learning (ML) may allow for improved discernment of hemodynamics and oxygen delivery compared to standard invasive monitoring. We hypothesized that an ML algorithm could predict impaired delivery of oxygen (IDO) with comparable discrimination to invasive mixed venous oxygen saturation (SvO) measurement.

Methods: A total of 230 patients not on mechanical circulatory support (MCS) managed with a pulmonary artery catheter (PAC) were identified from 1012 patients admitted to a single cardiovascular intensive care unit (CVICU) between April 2021 and January 2022.

Toward expert-level medical question answering with large language models.

Large language models (LLMs) have shown promise in medical question answering, with Med-PaLM being the first to exceed a 'passing' score in United States Medical Licensing Examination style questions. However, challenges remain in long-form medical question answering and handling real-world workflows. Here, we present Med-PaLM 2, which bridges these gaps with a combination of base LLM improvements, medical domain fine-tuning and new strategies for improving reasoning and grounding through ensemble refinement and chain of retrieval.

Transplantation of a genetically modified porcine heart into a live human.

Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen.

High-efficiency base editing in the retina in primates and human tissues.

Stargardt disease is a currently untreatable, inherited neurodegenerative disease that leads to macular degeneration and blindness due to loss-of-function mutations in the ABCA4 gene. We have designed a dual adeno-associated viral vector encoding a split-intein adenine base editor to correct the most common mutation in ABCA4 (c.5882G>A, p.

Molecular Evolution of Paralogous Cold Shock Proteins in E. coli: A Study of Asymmetric Divergence and Protein Functional Networks.

Nine homologous Cold Shock Proteins (Csps) have been recognized in the E.coli Cold Shock Domain gene family. These Csps function as RNA chaperones.

Effect of phenylephrine infusion on postpartum blood loss after cesarean delivery: a placebo-controlled, randomized clinical trial.

Background: Preclinical studies have documented the role of alpha-adrenergic agonists in myometrial contraction. Phenylephrine is frequently used to prevent and treat post-spinal hypotension during cesarean delivery. We hypothesized phenylephrine would reduce postpartum blood loss due to alpha-1 receptor-mediated uterine and vascular smooth muscle contraction.

Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma.

Background: Talquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma.

Methods: We conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study.

Validation and Recalibration of a Model for Predicting Surgical-Site Infection After Pelvic Organ Prolapse Surgery.

Introduction And Hypothesis: The objective was to externally validate and recalibrate a previously developed model for predicting postoperative surgical-site infection (SSI) after pelvic organ prolapse (POP) surgery.

Methods: This study utilized a previously validated model for predicting post-POP surgery SSI within 90 days of surgery using a Medicare population. For this study, the model was externally validated and recalibrated using the Premier Healthcare Database (PHD) and the National Surgical Quality Improvement Project (NSQIP) database.

Both English- and Spanish-Language Anterior Cruciate Ligament Reconstruction Online Patient Education Materials Are Written at Higher-Than-Recommended Reading Levels.

Purpose: To examine the overall reading levels of anterior cruciate ligament reconstruction online patient education materials (OPEMs) written in English and Spanish.

Methods: We conducted Google searches for OPEMs using "ACL surgery" and "" as English and Spanish search terms, respectively. Several measures of readability were used to analyze 25 English-language OPEMs (Flesch Reading Ease, Flesch Reading Ease Grade Level, Flesch-Kincaid Grade Level, Coleman-Liau Index, Gunning Fog Index, and Simple Measure of Gobbledygook) and 25 Spanish-language OPEMs (Fernández-Huerta Index, Fernández-Huerta Grade Level, and Índice de Legibilidad de Flesch-Szigriszt).

Obstacle Course Races Present a Risk of Musculoskeletal, Knee, and Anterior Cruciate Ligament Injury, Especially in High-Impact Landing Maneuvers and Female Athletes: A Systematic Review.

Purpose: To determine the incidence rate (IR) of anterior cruciate ligament (ACL) and associated musculoskeletal injuries in recreational and/or military-training obstacle course races (OCRs) and to determine whether there are any risk factors or features of OCRs impacting the rate of ACL injury in race participants.

Methods: This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies were identified using the following electronic databases: PubMed, EMBASE, Cochrane, and Scopus.