Surgical nonunion treatment of large-sized defects of femur and tibia based on the diamond concept.

Aims: The aim of this study was to evaluate the radiological outcome of patients with large bone defects in the femur and tibia who were treated according to the guidelines of the diamond concept in our department (Centre for Orthopedics, Trauma Surgery, and Paraplegiology).

Methods: The following retrospective, descriptive analysis consists of patients treated in our department between January 2010 and December 2021. In total, 628 patients were registered, of whom 108 presented with a large-sized defect (≥ 5 cm).

Outcomes of Standard-Risk Multiple Myeloma Patients Who Undergo Upfront Autologous Hematopoietic Stem Cell Transplantation.

Background: Patients with multiple myeloma without high-risk cytogenetic abnormalities are classified as having standard-risk MM (SRMM), and data focusing on their outcomes after autologous stem-cell transplantation (autoHCT) are limited.

Objective: To evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes.

Study Design: Single-center retrospective analysis that included consecutive MM patients who received upfront autoHCT between 2013-2021, had available cytogenetic information and had no high-risk chromosomal abnormalities on fluorescence in situ hybridization (FISH), defined as t(4;14), t(14;16), del(17p) or 1q21 gain or amplification.

Impact of glucagon-Like peptide-1 agonists in optimizing abdominal wall Reconstruction patients.

Purpose: Pre-optimization of obese patients prior to abdominal wall reconstruction (AWR) is essential in mitigating their increased preoperative risks. Traditionally diet, exercising, bariatric surgery are the tools typically prescribed for weight loss. The advent of glucagon-like peptide-1 agonists (GLP-1A) which stimulate insulin secretion and inhibit gastric emptying have improved the weight loss armamentarium.

Cryo-EM characterization of the anydromuropeptide permease AmpG central to bacterial fitness and β-lactam antibiotic resistance.

Bacteria invest significant resources into the continuous creation and tailoring of their essential protective peptidoglycan (PG) cell wall. Several soluble PG biosynthesis products in the periplasm are transported to the cytosol for recycling, leading to enhanced bacterial fitness. GlcNAc-1,6-anhydroMurNAc and peptide variants are transported by the essential major facilitator superfamily importer AmpG in Gram-negative pathogens including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa.

Optimal infused CD34 cell dose in multiple myeloma patients undergoing upfront autologous hematopoietic stem cell transplantation.

Autologous transplantation remains the standard of care for eligible multiple myeloma (MM) patients, yet optimal CD34 cell dose remains unclear. We conducted a retrospective study on MM patients undergoing upfront transplant between 2005 and 2021 and divided them into low (≤2.5 × 10 cells/kg) and high (>2.

Antibiotic-induced loss of gut microbiome metabolic output correlates with clinical responses to CAR T-cell therapy.

Antibiotic-induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cell therapies. In this study, we observed that prior exposure to broad-spectrum ABX with extended anaerobic coverage like piperacillin-tazobactam and meropenem was associated with worsened anti-CD19 CAR-T therapy survival outcomes in large B-cell lymphoma patients (n=422), compared to other ABX classes. In a discovery subset of these patients (n=67), we found that the use of these ABX was in turn associated with substantial dysbiosis of gut microbiome function, resulting in significant alterations of the gut and blood metabolome, including microbial effectors such as short-chain fatty acids (SCFAs) and other anionic metabolites, findings that were largely reproduced in an external validation cohort (n=58).

Right ventriculography to guide left bundle branch pacing in pacing-induced cardiomyopathy: a novel case report.

Background: There is emerging evidence for the potential utility of left bundle branch area pacing (LBBAP), as an alternative to conventional cardiac resynchronization therapy (CRT). The utility of right ventriculography by way of power injector to facilitate lead placement has not yet been reported in the literature.

Case Summary: A 79-year-old female, with a background of poorly rate-controlled atrial fibrillation, presented with worsening dyspnoea.

Long-Term Outcomes of Adjuvant Trastuzumab for 9 Weeks or 1 Year for ERBB2-Positive Breast Cancer: A Secondary Analysis of the SOLD Randomized Clinical Trial.

Importance: The standard adjuvant treatment for patients with ERRB2-positive breast cancer is chemotherapy plus 1 year of trastuzumab. Shorter durations of trastuzumab administration improve cardiac safety, but more information is needed about their effect on survival.

Objective: To compare survival outcomes after 9-week vs 1-year administration of trastuzumab with the same adjuvant chemotherapy.

Multiple Sex- and Circuit-Specific Mechanisms Underlie Exercise-Induced Stress Resistance.

Prior physical activity reduces the risk of future stress-related mental health disorders including depression, anxiety, and post-traumatic stress disorder. Rodents allowed to engage in voluntary wheel running are similarly protected from behavioral consequences of stress. The present review summarizes current knowledge on mechanisms underlying exercise-induced stress resistance.

Occupational exposure to malaria, leishmaniasis and arbovirus vectors in endemic regions: A systematic review.

Vector-borne diseases, including dengue, leishmaniasis and malaria, may be more common among individuals whose occupations or behaviours bring them into frequent contact with these disease vectors outside of their homes. A systematic review was conducted to ascertain at-risk occupations and situations that put individuals at increased risk of exposure to these disease vectors in endemic regions and identify the most suitable interventions for each exposure. The review was conducted in accordance with PRISMA guidelines on articles published between 1945 and October 2021, searched in 16 online databases.

Predictors of the efficacy of His bundle pacing in patients with a prolonged PR interval: A stratified analysis of the HOPE-HF randomized controlled trial.

Aims: The randomized, double-blind, placebo-controlled HOPE-HF trial assessed the benefit of atrio-ventricular (AV) delay optimization delivered using His bundle pacing. It recruited patients with left ventricular ejection fraction ≤40%, PR interval ≥200 ms, and baseline QRS ≤140 ms or right bundle branch block. Overall, there was no significant increase in peak oxygen uptake (VOmax) but there was significant improvement in heart failure specific quality of life.

Mobile-CRISPRi protocol optimization for .

Mobile clustered regularly interspaced palindromic repeats interference (Mobile-CRISPRi) is an established method for bacterial gene expression knockdown. The deactivated Cas9 protein and guide RNA are isopropyl β-D-1-thiogalactopyranoside inducible, and all components are integrated into the chromosome via Tn transposition. Here, we optimized methods specific for applying Mobile-CRISPRi in multiple species.

In T1DM without CVD, the LIFE-T1D model predicted lifetime risk for CVD and non-CVD mortality.

Helmink MAG, Hageman SHJ, Eliasson B, et al. Diabetes Obes Metab. 2024;26:2229-2238.

Fluorescence lifetime imaging with distance and ranging using a miniaturised SPAD system.

In this work we demonstrate a miniaturised imaging system based around a time-gated SPAD array operating in a "chip-on-tip" manner. Two versions of the system are demonstrated, each measuring 23 mm × 23 mm × 28 mm with differing fields of view and working distances. Initial tests demonstrate contrast between materials in widefield fluorescence imaging (WFLIm) mode, with frame rates of > 2 Hz achievable.

Trends in Outcomes After Upfront Autologous Transplant for Multiple Myeloma Over Three Decades.

Upfront autologous stem cell transplantation (auto-SCT) remains standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM), although recently its role has been questioned. The aim of the study was to evaluate trends in patient characteristics, treatment, and outcomes of NDMM who underwent upfront auto-SCT over three decades. We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-SCT at MD Anderson Cancer Center between 1988 to 2021.

Mobile-CRISPRi as a powerful tool for modulating gene expression.

CRISPRi (Clustered Regularly Interspaced Palindromic Repeats interference) is a gene knockdown method that uses a deactivated Cas9 protein (dCas9) that binds a specific gene target locus dictated by an encoded guide RNA (sgRNA) to block transcription. Mobile-CRISPRi is a suite of modular vectors that enable CRISPRi knockdowns in diverse bacteria by integrating IPTG-inducible and genes into the genome using Tn transposition. Here, we show that the Mobile-CRISPRi system functions robustly and specifically in multiple species: , , , , and .

Pharmacological manipulations of the dorsomedial and dorsolateral striatum during fear extinction reveal opposing roles in fear renewal.

Systemic manipulations that enhance dopamine (DA) transmission around the time of fear extinction can strengthen fear extinction and reduce conditioned fear relapse. Prior studies investigating the brain regions where DA augments fear extinction focus on targets of mesolimbic and mesocortical DA systems originating in the ventral tegmental area, given the role of these DA neurons in prediction error. The dorsal striatum (DS), a primary target of the nigrostriatal DA system originating in the substantia nigra (SN), is implicated in behaviors beyond its canonical role in movement, such as reward and punishment, goal-directed action, and stimulus-response associations, but whether DS DA contributes to fear extinction is unknown.