Lisfranc Fracture-dislocation With Extensor Hallucis Brevis Tendon Interposition: A Case Report.

Case: A 14-year-old adolescent girl sustained a Lisfranc fracture-dislocation with an interposed extensor hallucis brevis (EHB) tendon. Following multiple failed attempts at closed reduction in both the emergency department and the operating room, the patient was treated in a staged manner with temporizing closed reduction and percutaneous pinning in improved alignment, followed by definitive open reduction and internal fixation once soft tissues allowed.

Conclusions: Anatomic reduction and stable fixation of Lisfranc injuries is vital to regain stability and reduce the risk of midfoot arthritis and collapse.

Treatment With Avacopan in Patients With Respiratory Tract Manifestations of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Objective: The ADVOCATE trial demonstrated that treatment of active granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) with avacopan was noninferior in achieving remission at week 26 and superior for sustained remission at week 52 compared with a prednisone taper. This analysis of ADVOCATE evaluated the efficacy and safety of avacopan in patients with ear, nose, throat (ENT), or lung manifestations.

Methods: This post hoc analysis included patients enrolled in ADVOCATE with ENT or lung manifestations at baseline.

Role of NLRP3 Inflammasome in Chronic Pain and Alzheimer's Disease-A Review.

The coexistence of Alzheimer's disease (AD) and chronic pain (CP) in the elderly population has been extensively documented, and a growing body of evidence supports the potential interconnections between these two conditions. This comprehensive review explores the mechanisms by which CP may contribute to the development and progression of AD, with a particular focus on neuroinflammatory pathways and the role of microglia, as well as the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The review proposes that prolonged pain processing in critical brain regions can dysregulate the activity of the NLRP3 inflammasome within microglia, leading to the overproduction of pro-inflammatory cytokines and excessive oxidative stress in these regions.

Symptomatic Improvement in Adults and Adolescents With Eosinophilic Esophagitis Requires Higher Systemic Dupilumab Exposure Than Histologic Response.

Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications.

Methods: Results for the phase 3 LIBERTY EoE TREET study coprimary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses.

Results: A steep initial relationship then plateau was observed between higher dupilumab steady-state trough concentrations and decreased eosinophilic infiltration at week 24, whereas a graded exposure-response relationship was observed for symptomatic improvement at week 24.

Different PD-L1 Assays Reveal Distinct Immunobiology and Clinical Outcomes in Urothelial Cancer.

Testing for PD-L1 expression by immunohistochemistry (IHC) is used to predict immune checkpoint blockade (ICB) benefit but has performed inconsistently in urothelial cancer (UC) clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on UC samples using the SP142 and 22C3 assays from the phase 3 IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays (PD-L1 double positive; PD-L1DP), PD-L1 positive by the SP142 assay only (SP142 single positive; SP142SP), PD-L1 positive by the 22C3 assay only (22C3 single positive; 22C3SP), and PD-L1 negative by both assays double negative (PD-L1 double negative; PD-L1DN).

Genomic analyses reveal high diversity and rapid evolution of within a neonatal intensive care unit in Delhi, India.

causes life-threatening infections in immunocompromised hosts, including hospitalized neonates. This pathogen is intrinsically resistant to fluconazole, while uncommon strains resistant to multiple antifungal drugs, including voriconazole, amphotericin B, and echinocandins, have also been reported from healthcare environments. Thus, understanding how spread, persist, and adapt to healthcare settings could help us develop better infection management strategies.

An Enigmatic Wild Passerine Mortality Event in the Eastern United States.

The ability to rapidly respond to wildlife health events is essential. However, such events are often unpredictable, especially with anthropogenic disturbances and climate-related environmental changes driving unforeseen threats. Many events also are short-lived and go undocumented, making it difficult to draw on lessons learned from past investigations.

Bridging the Gaps in Atrial Fibrillation Management in the Emergency Department.

Atrial fibrillation (AF) frequently presents in emergency departments (EDs), contributing significantly to adverse cardiovascular outcomes. Despite established guidelines, ED management of AF often varies, revealing important gaps in care. This review addresses specific challenges in AF management for patients in the ED, including the nuances of rate versus rhythm control, the timing of anticoagulation initiation, and patient disposition.

A New Risk Prediction Model for the Assessment of Myocardial Injury in Elderly Patients Undergoing Non-Elective Surgery.

Currently, recommended pre-operative risk assessment models including the revised cardiac risk index (RCRI) are not very effective in predicting postoperative myocardial damage after non-elective surgery, especially for elderly patients. This study aimed to create a new risk prediction model to assess myocardial injury after non-cardiac surgery (MINS) in elderly patients and compare it with the RCRI, a well-known pre-operative risk prediction model. This retrospective study included 370 elderly patients who were over 65 years of age and had non-elective surgery in a tertiary hospital.

Coronavirus Disease 2019 (COVID-19) Real World Data Infrastructure: A Big-Data Resource for Study of the Impact of COVID-19 in Patient Populations With Immunocompromising Conditions.

Background: We developed a United States-based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials.

Methods: The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and End Results registry data.

Results: The CRWDi contains 4 cohorts: patients with cancer; patients with rheumatic diseases receiving pharmacotherapy; noncancer solid organ and hematopoietic stem cell transplant recipients; and people from the general population including adults and pediatric patients.

Review of Statistical Considerations and Data Imputation Methodologies in Psoriasis Clinical Trials.

Numerous clinical trials have established that various biologic and oral small-molecule therapies are efficacious in patients with psoriasis. However, as there are limited head-to-head trials, healthcare providers may compare results across multiple trials when providing treatment recommendations. Direct comparisons among agents are challenging because psoriasis trials differ in terms of study design, patient population, and data analysis methodologies.

Human iPSC Reprogramming Success: The Impact of Approaches and Source Materials.

Since their discovery, human induced pluripotent stem cells (hiPSCs) have been instrumental in biomedical research, particularly in the fields of disease modelling, drug screening and regenerative therapies. Their use has significantly increased over recent years driven by the ability of hiPSCs to provide differentiated cell models without requiring embryonic stem cells. Furthermore, the transition from integrating to non-integrating reprogramming methodologies has contributed to the increase in utilisation.

Assessment of oral health status among occupational chefs and pantry workers in Hyderabad city.

Background: The chefs and pantry workers environment plays a crucial role in the general and oral health. These workers have some unusual work timings and have a lot of stress and anxiety, and they also consume tobacco, alcohol, and smoke the cigarettes, which has a greater impact on oral health.

Material And Methods: A total of 86 kitchen workers (53 chefs and 33 pantry workers) of ten well-known restaurants in Hyderabad city were included.

Ethnic and racial differences in children and young people with respiratory and neurological post-acute sequelae of SARS-CoV-2: an electronic health record-based cohort study from the RECOVER Initiative.

Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health.

Methods: We conducted a retrospective cohort study of individuals <21 years seeking care at 24 health systems across the U.

Methylmercury in subarctic amphibians: environmental gradients, bioaccumulation, and estimated flux.

Rapid warming in polar regions is causing large changes to ecosystems, including altering environmentally available mercury (Hg). Although subarctic freshwater systems have simple vertebrate communities, Hg in amphibians remains unexplored. We measured total Hg (THg) in wetland sediments and methylmercury (MeHg) in multiple life-stages (eggs to adults) of wood frogs (Rana sylvatica) and larval boreal chorus frogs (Pseudacris maculata) from up to 25 wetlands near Churchill, Manitoba (Canada), during the summers of 2018-2019.

Pharmacokinetics of Nivolumab and Erythropoietin in a Rat Model of Diet-Induced Obesity.

Purpose: To investigate how obesity affects the pharmacokinetics of biologics in a rat model.

Method: Male Long-Evans rats were fed a high-fat diet from the age of 3 weeks and development of obesity was monitored by measuring body size and composition (fat and lean mass). The animals received nivolumab (1 and 8 mg/kg) or recombinant human erythropoietin (rHuEPO, 1000 IU/kg) by intravenous or subcutaneous injection.

Microstructure response of concentrated suspensions to flow reversal.

We study experimentally at the macroscopic and microstructure scale a dense suspension of non-Brownian neutrally buoyant spherical particles experiencing periodic reversals of flow at constant rate between parallel plates and tracked individually. We first characterize the quasi-steady state reached at the end of half periods. The volume fraction of particles increases from the walls to the center as a result of migration induced by the nonuniform strain rate.

Schizophrenia and retention in HIV care among adults insured through Medicaid in the United States: a population-based retrospective cohort study.

Background: People with schizophrenia spectrum disorders are at elevated risk of HIV, and people with both HIV and schizophrenia are at elevated risk of death compared to individuals with either diagnosis alone. Limited research has assessed the HIV care cascade, and in particular retention in care, among people with HIV (PWH) and schizophrenia in the U.S.

Opportunities for More Tailored Approaches to Genotoxicity Testing and Carcinogenicity Strategy for Oligonucleotide Therapeutics: Outcome of an Industry Survey.

The Oligonucleotide Nonclinical Working Group (WG) of the European Federation of Pharmaceutical Industries and Associations conducted an industry survey to understand current practices and regulatory expectations for genotoxicity and carcinogenicity assessment of oligonucleotide therapeutics (ONTs), along with historical genotoxicity testing results. The survey, involving 29 pharmaceutical and biotechnology companies, revealed a consistent absence of genotoxicity across a diverse range of oligonucleotide classes and chemistries, consistent with previous observations. Despite the lack of genotoxicity, companies continue to follow standard testing guidelines, with only limited divergence.

Intratumoral or Subcutaneous MK-2118, a Non-Cyclic Dinucleotide STING Agonist, With or Without Pembrolizumab for Advanced or Metastatic Solid Tumors or Lymphomas.

Background: We evaluated the non-cyclic dinucleotide stimulator of interferon genes agonist MK-2118 ± pembrolizumab in patients with advanced solid tumors or lymphomas.

Methods: This first-in-human study (NCT03249792) enrolled patients with refractory, advanced solid tumors or lymphomas. Patients received intratumoral (IT) MK-2118 100-20,000 µg (arm 1), IT MK-2118 900-15,000 µg plus intravenous (IV) pembrolizumab 200 mg every 3 weeks (Q3W; arm 2), or subcutaneous (SC) MK-2118 5000-150,000 µg plus IV pembrolizumab 200 mg Q3W (arm 4); arm 3 (visceral injection of MK-2118) was not pursued.

Coupling high-throughput and modeling approaches to streamline early-stage process development for biologics.

Platforms have long been implemented for downstream process development of monoclonal antibodies (mAbs) to streamline development and reduce timelines. These platforms are also increasingly being used for other complex biologics modalities. While development has traditionally been conducted at the lab bench scale in a sequential manner, automated miniaturized and parallelized approaches like RoboColumns and resin plates have also been implemented for chromatographic screening.