Outcome Measures for Sjögren Disease-Novel Developments and Further Needs.

Sjögren disease (SjD) is a systemic autoimmune disorder affecting both children and adults, with a wide range of clinical phenotypes. It remains a challenging condition to recognise and diagnose early and manage effectively. The heterogeneous nature of the presentation, variable disease course and overlapping symptoms with other autoimmune conditions often result in delayed diagnosis.

Modulation of Lymphotoxin β Surface Expression by Kaposi's Sarcoma-Associated Herpesvirus K3 Through Glycosylation Interference.

Kaposi's sarcoma-associated herpesvirus (KSHV) employs diverse mechanisms to subvert host immune responses, contributing to its infection and pathogenicity. As an immune evasion strategy, KSHV encodes the Membrane-Associated RING-CH (MARCH)-family E3 ligases, K3, and K5, which target and remove several immune regulators from the cell surface. In this study, we investigate the impact of K3 and K5 on lymphotoxin receptor (LTβR) ligands, LTβ and LIGHT, which are type II transmembrane proteins and function as pivotal immune mediators during virus infection.

The long-term success of cardiovascular surgery in Takayasu arteritis: 48 years of experience in Mexico, beyond forefront techniques.

Background: Takayasu arteritis (TA) affects medium and large caliber arteries causing stenosis, occlusion, or aneurysms. It has great predilection for the aortic arch, subclavian and extracranial arteries. The global prevalence is of 1% to 2% per million inhabitants, which varies by geographical region.

Improving cefazolin administration for surgical prophylaxis in reported penicillin allergy: A retrospective study of a health system intervention.

Background: Cefazolin is the most common first-line antibiotic to prevent surgical-site infections. Patients with penicillin allergy labels often receive alternative antibiotics, which is associated with increased rates of surgical-site infections, multi-drug-resistant infections, and cost.

Objective: We sought to determine whether a hospital-wide guideline recommending first-line surgical prophylaxis in patients with penicillin allergy labels can increase the use of cefazolin without compromising safety.

OA-MEN: a fusion deep learning approach for enhanced accuracy in knee osteoarthritis detection and classification using X-Ray imaging.

Background: Knee osteoarthritis (KOA) constitutes the prevailing manifestation of arthritis. Radiographs function as a common modality for primary screening; however, traditional X-ray evaluation of osteoarthritis confronts challenges such as reduced sensitivity, subjective interpretation, and heightened misdiagnosis rates. The objective of this investigation is to enhance the validation and optimization of accuracy and efficiency in KOA assessment by utilizing fusion deep learning techniques.

Selection and Characterization of a DNA Aptamer Recognizing High Mobility Group Box 1 Protein (HMGB1) and Enhancing Its Pro-inflammatory Activity.

Background: High mobility group box 1 (HMGB1) plays an essential role in various pathological conditions, including inflammation, fibrosis, autoimmune diseases, and carcinogenesis. The quantification of HMGB1 in body fluids holds promise for clinical applications.

Objectives: This study aimed to isolate high-affinity single-stranded DNA (ssDNA) aptamers that target HMGB1.

A Scleroderma and Raynaud's UK (SRUK) national survey to explore rheumatologists' awareness, approaches to diagnosis and management and training needs within systemic sclerosis.

Objectives: Patients' outcomes and experiences can be affected by rheumatologist knowledge and awareness of systemic sclerosis (SSc). Our survey, directed at UK-based rheumatologists, aimed to expand our understanding of the above points along with their ability to keep up to date with guidelines defining best practice.

Methods: Rheumatologists were invited to participate in an online survey, with the results analysed and presented descriptively and graphically by SRUK.

Metabolic reprogramming and macrophage expansion define ACPA-negative rheumatoid arthritis: insights from single-cell RNA sequencing.

Background: Anti-citrullinated peptide antibodies (ACPA)-negative (ACPA-) rheumatoid arthritis (RA) presents significant diagnostic and therapeutic challenges due to the absence of specific biomarkers, underscoring the need to elucidate its distinctive cellular and metabolic profiles for more targeted interventions.

Methods: Single-cell RNA sequencing data from peripheral blood mononuclear cells (PBMCs) and synovial tissues of patients with ACPA- and ACPA+ RA, as well as healthy controls, were analyzed. Immune cell populations were classified based on clustering and marker gene expression, with pseudotime trajectory analysis, weighted gene co-expression network analysis (WGCNA), and transcription factor network inference providing further insights.

New Insights on Childhood Lupus Nephritis.

Approximately one in five patients with systemic lupus erythematosus (SLE) has disease-onset during childhood (cSLE). Lupus nephritis is more common in cSLE than adult-onset SLE and is associated with significant and increased morbidity and mortality. In this article, we review lupus nephritis in cSLE, including pathogenesis, diagnosis, biomarkers, and management through PUBMED search between July and December 2024.

Gait speed assessment in confined spaces: Development of a novel automated 4-m static-start test to measure dynamic-start gait speed.

Objectives: To promote standardization and feasible measurements of gait speed across the field, we developed a device that used light detection and ranging (LiDAR) technology to measure gait speed from a standing-start testing procedure conducted on a 4-m total walkway. We compared this automated (LiDAR-based) standing-start 4-m gait speed test (AS-4MG) with automated and manual (stopwatch-based) dynamic-start 4-m gait speed tests (AD-4MG and MD-4MG, respectively) on between-method agreement, measurement repeatability, and predictive validity with functional outcomes.

Methods: A sample of 48 community-dwelling adults (mean [SD], 69 [9] years) participated in this method comparison study.

The Association Between Myasthenia Gravis and Higher Extrathymic Cancer Risk.

Background: Myasthenia gravis (MG) is strongly associated with thymic tumors, but whether it is also associated with extrathymic cancers is debatable or whether MG can be considered a paraneoplastic disorder for extrathymic cancers.

Methods: This is a retrospective analysis of the MG cohort for 23 years' time (January 2000 to May 2023), extracting cancer rates with clinical, electrophysiological, and biochemical cancer associations and the effect of chronic medications.

Results: We identified 436 patients with MG and 3924 controls.

Physician Views and Attitudes Regarding Tobacco-Cessation Strategies for Patients with Rheumatoid Arthritis.

Objective: In this study, we explored physicians' level of experience with patients with rheumatoid arthritis (RA) who used tobacco; their views on the effects of tobacco use on the efficacy of RA treatments; and their experiences and attitudes with respect to tobacco cessation programs.

Methods: We conducted qualitative, semi-structured interviews of 20 physicians (10 primary-care physicians [PCPs] and 10 rheumatologists).

Results: The physicians had been in clinical practice for a mean of 9.

Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE.

Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the small blood vessels can lead to ischemia, and frequently reported by SLE patients. Using whole blood RNA samples, we asked whether gene signatures discriminate SLE patients with coronary microvascular dysfunction (CMD) on cardiac MRI (n = 4) from those without (n = 7) and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD.

Joint replacement for rheumatoid arthritis: When, why, and how! Insights from an orthopedic surgeon.

The past several decades have seen significant advancements in joint replacement surgery for rheumatoid arthritis (RA). Joint replacement procedures have become vital options for patients with severe joint damage and functional impairment. There has been an increased emphasis on personalized surgical strategies that tailor joint replacement decisions based on a patient's unique clinical characteristics and the extent of joint damage.

Regulation of UCP1 expression by PPARα and pemafibrate in human beige adipocytes.

Aims: Thermogenic adipocytes are able to dissipate energy as heat from lipids and carbohydrates through enhanced uncoupled respiration, due to UCP1 activity. PPAR family of transcription factors plays an important role in adipocyte biology. The purpose of this work was to characterize the role of PPARα and pemafibrate in the control of thermogenic adipocyte formation and function.

A single-arm, phase II study of sotorasib plus carboplatin/pemetrexed in advanced non-squamous non-small cell lung cancer patients with KRAS G12C mutation (WJOG14821L, SCARLET).

Background: The efficacy and safety of sotorasib plus platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous non-small cell lung cancer (non-Sq NSCLC) were previously reported with limited follow-up period.

Method: SCARLET was a single-arm phase II study of chemotherapy-naïve patients with KRAS G12C-mutated non-Sq NSCLC. Participants received sotorasib 960 mg daily plus four cycles of carboplatin (area under the curve, 5)/pemetrexed 500 mg/m, followed by sotorasib/pemetrexed until disease progression.

Low Survival Due to Higher Risk of Relapse and Nonrelapse Mortality After Allogeneic HSCT in ATL Compared with AML and ALL.

Background: Patients with adult T-cell leukemia/lymphoma (ATL) are considered to have worse outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) than patients with other hematological malignancies, owing to high risk of relapse and immunocompromised status. However, no studies have compared transplant outcomes between patients with ATL and those with other hematological malignancies using a large-scale database.

Objectives: To compare transplant outcomes between patients with ATL and those with other leukemias and to identify factors contributing to worse transplant outcomes in ATL patients.

Impairment of the T cell memory response in chronic lymphocytic leukemia patients after SARS-CoV-2 vaccination.

CLL patients face increased vulnerability to COVID-19 because of weakened immune systems from comorbidities and treatments. Therefore, the need for these patients of vaccination is of outermost importance. In our study we have evaluated T cell-mediated responses to COVID19 vaccines by performing the activation-induced markers (AIM) assay which allows to determine spike-specific CD4+ and CD8+ T cell responses.

Investigating the role of the metabolic score for visceral Fat in assessing the prevalence of chronic kidney disease from the NHANES 1999-2018.

This study investigates the association between the Metabolic Score for Visceral Fat (METS-VF) and chronic kidney disease (CKD), assessing METS-VF as a potential predictor of CKD risk. Utilizing data from the 1999-2018 National Health and Nutrition Examination Survey (NHANES), this cross-sectional study included 24,387 adult participants. Multivariable logistic regression, restricted cubic spline models, and threshold effect analyses were employed to explore the relationship.

Reverse mutational scanning of SARS-CoV-2 spike BA.2.86 identifies epitopes contributing to immune escape from polyclonal sera.

The recently detected Omicron BA.2.86 lineage contains more than 30 amino acid mutations relative to BA.

Quantitative liver function imaging and whole genome sequencing - Effective modalities for a new era in personalised decision-making for operable colorectal liver metastases?

Background: The optimal strategy for patients with colorectal liver metastases (CRLM) is unclear. The Precision1 prospective, observational trial assessed whether pre-operative functional imaging and whole genome sequencing (WGS), could enhance individualized decision-making.

Methods: Patients with CRLM considered for hepatectomy were recruited.

Primary Antibody Deficiencies: Curation Of Gene-Disease Relationships Using A ClinGen Validation Framework.

Background: The Clinical Genome Resource (ClinGen) is an international collaborative effort between scientists and clinicians, diagnostic and research laboratories as well as the patient community. Using a standardized framework, ClinGen has established guidelines to classify gene-disease relationships as Definitive, Strong, Moderate, and Limited based on available scientific and clinical evidence. When the genetic and functional evidence for a gene-disease relationship has conflicting interpretations or contradictory evidence, they can be Disputed or Refuted.

A simulation study showed that linear regression and Mann-Whitney test can be used to analyse the Days Alive and at Home by day 30 (DAH30) outcome in a randomized controlled trial.

Objective: The aims of the work were to consider the properties of the DAH30 from a statistical perspective, and to conduct a simulation study exploring the use of simple (unadjusted) linear regression and Mann-Whitney test as the method of analysis reflect realised analysis options.

Study Design And Setting: The days alive and at home by day 30 (DAH30) has been proposed a patient-centric outcome, and clinically relevant outcome suitable for clinical trials. It has unusual statistical properties, and suitability of standard statistical analysis methods is unclear.

Immunosuppressive therapy to treat newly diagnosed primary heart involvement in patients with systemic sclerosis: An Italian cardiac magnetic resonance based study.

Background: Primary heart involvement (pHI) is frequent in systemic sclerosis (SSc), and is associated with a poor prognosis. Therapeutic strategies to treat SSc-pHI are not yet defined.

Objectives: To evaluate the efficacy of immunosuppressive therapy on cardiac magnetic resonance (CMR) features in patients with CMR-proven SSc-pHI.