Sacituzumab tirumotecan (sac-TMT) is a novel anti-trophoblast cell-surface antigen 2 antibody-drug conjugate and has been approved for second-line and subsequent treatment of metastatic triple-negative breast cancer (TNBC) in China. This post-hoc exploratory study aims to further characterize the safety profile of sac-TMT to inform clinical practice.

This analysis was based on the safety set from the OptiTROP-Breast01 study, including all subjects who have received at least one dose of sac-TMT or treatment of physician's choice (TPC). Frequencies and patterns of the adverse events (AEs) were reported. Particular emphasis was placed on hematologic toxicities (including anemia, neutropenia, thrombocytopenia) and stomatitis, which were defined as key AEs in this study.

262 patients (130 for sac-TMT, 132 for TPC) were included. Median time to the onset of grade 3 or higher key AEs primarily occurred within the first two cycles. Most patients with key AEs in the sac-TMT arm ultimately recovered to grade 2 or lower, typically within 14 days. Efficacy was generally comparable among subgroups with early/late dose reduction (reduction within/after 2 months from treatment initiation), or without dose reduction of sac-TMT. Among patients with treatment duration more than 7 months, the incidence of treatment related AEs (TRAEs), including both any grade and grade 3 or higher TRAEs, decreased over time.

Sac-TMT demonstrated a manageable safety profile, with adverse events effectively managed through dose modification and appropriate supportive care without compromising its efficacy. Long-term use of sac-TMT further supports its manageable toxicity profile.

NCT05347134.

2022-04-26.

Icariin, a prenylated flavonoid glycoside from Epimedium species, is a representative dietary polyphenol with antioxidant, anti-inflammatory, and antitumor properties. Gastric cancer (GC) is a major non-communicable chronic disease characterized by complex molecular alterations and dysregulated redox homeostasis, yet the molecular targets underlying the potential anti-GC activity of icariin remain poorly defined. In this study, we integrated network pharmacology, bulk transcriptomic analysis (TCGA-STAD; GSE15497, GSE84437, GSE84433, and GSE26253), and single-cell RNA sequencing (GSE183904; 142,053 cells) to identify candidate icariin-associated genes in GC. NOX4 expression, prognostic value, and tumor microenvironment characteristics were systematically evaluated. A NOX4-positive endothelial cell (NOX4pos_Endo)-associated molecular subtyping strategy and a LASSO-Cox prognostic model were constructed and validated. Molecular docking and molecular dynamics simulation were performed to explore a potential interaction between icariin and NOX4, and AGS cells were used for in vitro validation. Network pharmacology identified 24 overlapping icariin-GC targets, among which NOX4 showed prominent prognostic relevance. NOX4 was upregulated in GC and associated with unfavorable prognosis across multiple cohorts. At the single-cell level, NOX4 was predominantly expressed in an endothelial subpopulation characterized by angiogenesis-, adhesion-, and extracellular matrix remodeling-related transcriptional features. Consensus clustering identified two molecular subtypes with distinct clinical outcomes and biological characteristics. A 5-gene prognostic model comprising SPIRE1, PLCH1, KCNS3, SLC27A2, and GRP showed moderate predictive performance across independent cohorts. Molecular docking suggested a potential icariin-NOX4 interaction involving Ser576 and Trp377, while molecular dynamics simulation supported the stability of the predicted binding pose. In AGS cells, icariin treatment was associated with reduced NOX4 expression and intracellular ROS levels. Overall, these findings identify NOX4 as a candidate icariin-associated regulatory node in GC and suggest that NOX4/ROS-related signaling may contribute to the cellular response to icariin. Further experimental studies are required to determine whether NOX4 is a direct molecular target of icariin and to clarify its therapeutic relevance.

Hopelessness is a predictor of depression and suicide. Suicide is a preventable cause of mortality worldwide. Although it is not among the leading overall causes of death in older adults due to the predominance of chronic non-communicable diseases, it remains an epidemiologically relevant issue in this stage of life. Globally, suicide ranked as the twenty-first leading cause of death in 2021, and approximately 16.6% of suicide-related deaths occurred among individuals aged 70 years and older. This highlights the need to assess associated psychological factors, such as hopelessness and depression, in the older adult population.

To evaluate the psychometric properties of the Beck Hopelessness Scale in Ecuadorian older adults by analyzing its factorial structure in one-, two-, and three-factor models, as well as its reliability and validity evidence, in order to determine the most appropriate structure for use in this population.

The internal factorial structure, reliability, and construct validity of the Beck Hopelessness Scale were analyzed in Ecuadorian older adults. A total of 2,233 participants were assessed. Analyses were conducted for one-, two-, and three-factor variants. Reliability was examined using McDonald's omega coefficient and Cronbach's alpha, while validity was assessed through confirmatory factor analysis using the Weighted Least Squares Mean and Variance Adjusted (WLSMV) estimation method.

The Beck Hopelessness Scale was evaluated in 2,233 Ecuadorian older adults (M = 74.02 years, SD = 8.96). Confirmatory factor analyses demonstrated an adequate fit for the one-, two-, and three-factor structures, with the one-factor model standing out due to its greater parsimony. The scale showed high internal consistency (ω = 0.933; α = 0.909) and adequate convergent validity (average variance extracted = 0.657). Factor loadings were significant across all models, supporting the relevance of the items for measuring hopelessness, although items D16 and D17 showed comparatively lower performance.

Overall, the findings support the validity and reliability of the scale for assessing hopelessness in Ecuadorian older adults.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed the management of type 2 diabetes and obesity. Gastrointestinal (GI) adverse events are the most common limitation of these therapies and a leading cause of discontinuation.

This narrative expert review synthesizes evidence from randomized controlled trials, observational studies, meta-analyses, and pharmacovigilance data to characterize the incidence, mechanisms, and clinical implications of GI adverse effects across approved agents and late-stage pipeline therapies.

Nausea, vomiting, diarrhea, and constipation are established class effects, occurring in approximately 30%-50% of patients, typically during initiation and dose escalation. These events are generally mild to moderate and manageable with dose titration and dietary modification. Mechanisms include delayed gastric emptying, central activation of emetic pathways, altered intestinal motility, and physiologic effects of rapid weight loss itself. Randomized trial data are reassuring for acute pancreatitis, with no class-level excess risk demonstrated; pharmacovigilance signals are most plausibly explained by diagnostic misclassification rather than true causal risk. Cholelithiasis shows a probable class-level association, substantially mediated by weight loss rather than direct receptor signaling. Peri-procedural data show increased residual gastric volume without confirmed aspiration events. Preliminary data on late-stage pipeline agents (retatrutide, survodutide, and cagrilintide-semaglutide) suggest a similar GI adverse event profile to approved agents, though evidence remains largely limited.

GI adverse events with GLP-1-based therapies are predictable and manageable. A proactive, patient-centered approach is essential to optimize adherence, safety, and clinical outcomes as newer agents expand the therapeutic landscape.

Mesenchymal stem cells (MSCs)/mesenchymal stromal cells and their extracellular vesicles (EVs), particularly exosomes, have emerged as therapeutic candidates in regenerative medicine due to their multipotency, low immunogenicity, and extensive immunomodulatory properties. This narrative review provides a narrative synthesis of MSC- and MSC-EV-mediated immunomodulation and its translational potential across four major autoimmune diseases: multiple sclerosis (MS), type 1 diabetes mellitus (T1D), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Mechanistically, MSCs regulate both innate and adaptive immune cell populations, modulate pro- and anti-inflammatory cytokine secretion, downregulate pro-inflammatory Th1/Th17 responses, and promote regulatory phenotypes, including regulatory T cells, regulatory B cells, and M2-polarized macrophages. Preclinical and clinical investigations suggest therapeutic potential across these diseases; however, much of the clinical evidence derives from small, early-phase, and frequently uncontrolled studies with limited follow-up, and safety outcomes vary according to MSC source, manufacturing process, dose, route of administration, and clinical indication. In these studies, the absence of serious adverse events does not constitute definitive evidence of long-term safety. Clinical studies have reported reductions in disease activity scores and inflammatory biomarkers, as well as improvements in disease-specific functional outcomes; however, these findings should be regarded as preliminary evidence of therapeutic potential rather than established efficacy across autoimmune diseases. Nonetheless, clinical translation remains hindered by manufacturing heterogeneity, variability in dosing, routes of administration, and treatment protocols, as well as challenges related to allogeneic immunogenicity and MSC-EV standardization. Overcoming these barriers will require standardized manufacturing and characterization protocols, alongside further investigation into the integration of MSC- and MSC-EV-based therapies within multimodal, personalized, and patient-tailored treatment frameworks.

Cardiometabolic diseases-principally cardiovascular disease, type 2 diabetes, and obesity-remain leading global drivers of premature mortality, disability, and healthcare expenditure, despite substantial advances in their biological understanding, risk assessment, and treatment. This narrative review critically examines why increasingly effective preventive interventions have failed to yield a commensurate reduction in population-level disease burden, identifying the biological, clinical, organizational, economic, and social factors that sustain this evidence-to-practice gap. It integrates evidence across three complementary dimensions: (1) The biological continuum, linking metabolic dysfunction, chronic low-grade inflammation, and cumulative exposure to apolipoprotein B (ApoB)-containing lipoproteins with atherosclerotic cardiovascular disease; (2) The clinical continuum, extending from early risk recognition and targeted diagnostic evaluation to individualized intervention and longitudinal reassessment; and (3) The organizational continuum, required to deliver coordinated, multidisciplinary prevention across health systems. Particular attention is given to total and lifetime cardiovascular risk, the clinical application and limitations of SCORE2 and SCORE2-OP, and the diagnostic challenges of identifying younger or apparently healthy individuals whose low short-term risk masks significant cumulative lifetime exposure. The review critically evaluates the causal role and clinical interpretation of ApoB-containing lipoproteins, including lipoprotein(a) [Lp(a)], and the complementary role of emerging biomarkers and subclinical atherosclerosis imaging, while carefully distinguishing enhanced risk prediction from demonstrated improvements in hard clinical outcomes. An educational and translational clinical vignette illustrates how the longitudinal interpretation of routine clinical and laboratory data supports proportionate assessment of persistent dyslipidemia, treatment response, and plausible primary and secondary contributors to cardiometabolic risk well before symptom onset. Rather than attributing borderline abnormalities to a single occult disorder, the vignette demonstrates how standardized confirmation, verification of medication exposure, etiological assessment, targeted referral, and structured reassessment can translate routine data into actionable preventive pathways. Ultimately, this analysis indicates that cardiometabolic prevention is constrained less by a lack of scientific evidence or effective pharmacotherapies than by delayed risk recognition, therapeutic inertia, poor treatment adherence, fragmented care pathways, limited multidisciplinary coordination, structural health inequalities, and the incomplete integration of clinical, laboratory, behavioral, environmental, and patient-reported data. Improving outcomes therefore demands a systemic shift from episodic, disease-specific management toward early, lifelong, proportionate, coordinated, equitable, and patient-centered cardiometabolic prevention-underpinned by implementation science, precision prevention, digital health solutions, health-economic evaluations, patient-reported outcome measures (PROMs), and patient-reported experience measures (PREMs).

To evaluate whether ultrasound-guided mini-midline catheter use (8-15 cm) is associated with treatment completion and safety outcomes compared with short peripheral catheters (<8 cm) for intravenous antimicrobial therapy lasting no more than 14 days, while additionally characterizing device specifications, peripheral drug compatibility, and cumulative vascular-access burden.

This single-center retrospective comparative cohort study included 134 hospitalized adults (55 mini-midline, 79 short PIVC) receiving planned intravenous antimicrobial therapy for 5-14 days. The primary endpoint was treatment completion through the index device. Secondary outcomes included catheter-related complications, re-catheterization, cumulative catheter burden, inflammatory markers, and descriptively summarized dwell time among devices with documented insertion and removal timestamps.

Treatment completion was 46/51 (90.2%) for mini-midlines and 79/79 (100.0%) for short PIVCs (unadjusted p=0.005; absolute RD -9.8%; Holm-adjusted p=0.015). Among devices with documented timestamps, median dwell time was 310.0 hours (12.9 days) for mini-midlines and 71.5 hours (3.0 days) for short PIVCs. Complication rates were low, with 3/55 mini-midline patients experiencing 5 catheter-related events and 0/79 short-PIVC patients experiencing catheter-related events. No bloodstream infection or symptomatic thrombosis occurred in either group. Mini-midline patients required fewer total PIVCs per treatment episode, while cumulative insertion attempts were 61 and 85 in the mini-midline and short-PIVC groups, respectively. Diabetes mellitus and ≥2 puncture attempts were associated with treatment non-completion in the mini-midline group.

Ultrasound-guided mini-midlines were associated with acceptable safety, longer observed peripheral dwell time, and reduced overall PIVC burden in selected hospitalized patients receiving up to 14 days of peripherally compatible intravenous antimicrobial therapy. Mini-midlines should be considered a complementary vascular-access strategy rather than a universal replacement for short PIVCs.

To investigate the ecological level associations and spatial co-variation among ambient air pollutants, Type 2 diabetes (T2D) related clinical markers, and gut microbiome composition in urban populations of Bhopal, India.

A cross-sectional ecological study was conducted involving 95 participants from three urban locations in Bhopal. Ambient air quality data, including PM_2.5, PM₁₀, NO_x, and SO₂, were obtained from local monitoring stations. Exposure assessment was based on location level ambient monitoring data corresponding to participants' residential localities rather than individual level personal exposure measurements. Clinical assessments were performed to measure T2D related metabolic parameters, and fecal samples were analyzed using full-length 16S rRNA sequencing to profile gut microbiome composition. Associations between pollutant levels, metabolic markers, and microbial taxa were evaluated using exploratory correlation and compositional analyses.

Variability was observed in both air pollutant concentrations and metabolic parameters. NO_x levels were positively correlated with glycemic indices, while particulate pollutants (PM_2.5 and PM₁₀) showed inconsistent and non-directional associations with metabolic markers. Gut microbiome analyses revealed broadly similar microbial community structures with subtle differences in diversity and composition across locations. Although variations were observed in selected microbial taxa, most genus-level differences did not remain statistically significant following multiple testing correction.

Air pollution and gut microbiome composition appear to have a descriptive role in metabolic health. The findings describe ecological level co-variation between ambient air pollution indicators, metabolic parameters, and gut microbiome composition across the study populations. Because the study design was cross-sectional and exposure assessment relied on location level monitoring data, the results should be interpreted as descriptive and hypothesis-generating rather than causal. Further longitudinal studies incorporating individual level exposure assessment and functional microbiome analyses are required to better evaluate these relationships.

The diabetes prevalence is increasing worldwide. Urban slum populations may face heightened vulnerability because of poverty, overcrowding, food insecurity, and limited access to healthcare. This scoping review mapped the available evidence on diabetes burden, determinants, interventions, healthcare utilization, and health-system challenges among people living in Iranian urban slums.

A scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR). PubMed/MEDLINE, Scopus, the Scientific Information Database (SID), and Magiran were searched without date or language restrictions. Peer-reviewed observational, qualitative, and interventional studies addressing diabetes in Iranian urban slums were eligible. Two reviewers independently performed study selection, quality appraisal, and data extraction.

Seven studies published between 2010 and 2024 were included: five cross-sectional studies, one community-based intervention, and one qualitative study. Two studies reported diabetes prevalence data in Rasht and Tabriz. One Interventional study in Yasouj and four study on health service utilization conducted in Tabriz. The mapped evidence identified financial, insurance, organizational, educational, and infrastructural barriers to diabetes care, as well as substantial unmet needs for medication support, glucose-monitoring supplies, self-management education, and communication with healthcare providers.

The available evidence suggests important diabetes-related care needs in the studied urban slum populations, but its limited geographical coverage and heterogeneous outcomes prevent national generalization. Broader studies are needed to quantify inequalities in awareness, treatment, complications, and service accessibility. Meanwhile, strengthening primary healthcare, insurance protection, and equity-oriented urban health policies may improve diabetes care in marginalized communities.

This study aimed to develop and validate a nomogram for predicting subsyndromal delirium (SSD) risk in critically ill patients with diabetes.

Critically ill adult patients with diabetes were retrospectively included in the emergency department of Peking Union Medical College Hospital from January 2025 to December 2025. Univariate and multivariate logistic regression analyses identified independent predictors for SSD. A nomogram was constructed based on these predictors. The model's performance was assessed by the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA).

A total of 297 patients with diabetes were included and the overall incidence of SSD was 38.7%. Univariate and multivariate analysis identified six independent predictors: higher NRS score, RASS score, APACHE II score, PSQI score, random blood glucose level at admission, and lower Barthel index. The nomogram incorporating these factors demonstrated good discrimination, with an AUC of 0.922 (95% CI: 0.891-0.953). Calibration curves showed good agreement between predicted and observed probabilities, and DCA indicated favorable clinical utility.

We developed and internally validated a nomogram for predicting SSD in critically ill patients with diabetes. The model may be useful for risk stratification, but prospective and external validation are required before clinical implementation.