Search Results (2,151)

Background/Objectives: The incidence of Crohn’s disease (CD) is increasing, necessitating effective long-term treatments. Ustekinumab (UST) is a biologic drug that blocks interleukins (ILs) 12/23. It has been approved for moderate-to-severe CD, but real-world long-term data in Chinese populations remain limited. Methods: This retrospective, single-center, cohort study included patients with CD who initiated UST between June 2020 and May 2025. The primary outcomes were clinical remission at week 24 and treatment persistence through week 96. Outcomes were calculated based on the number of patients with available data at each time point. Results: Of 110 patients screened, 95 were included; 69.5% were bio-naïve. The clinical remission rate was 86.3% (n = 82/95) at week 24, with 80% (n = 24/30) of those patients maintaining remission at week 96. Biological remission was achieved by 51.5% (n = 17/33) at week 24, with 47.8% (n = 11/23) maintaining it through week 96. No significant difference in efficacy was observed between UST monotherapy and combination therapy with 5-ASA. Multivariate analysis revealed absence of perianal lesion and normal serum albumin were associated with clinical remission at week 24. Endoscopic remission was documented in 39.3% (n = 11/28) of reassessed patients, with a significant reduction in Simple Endoscopic Score for Crohn’s Disease on UST. Analysis of drug survival on UST revealed no statistically significant difference (p = 0.2044) between bio-naïve and non-naïve patients. Adverse events were reported in 9.5% of patients, with none leading to treatment discontinuation. Conclusions: Ustekinumab was associated with significant long-term effectiveness and a favorable safety profile, including in bio-naïve and non-bio-naïve patients. Full article

Background: Diffuse large B-cell lymphoma (DLBCL) with TP53 abnormalities, corresponding to the LymphGen A53 molecular subtype, represents a biologically high-risk group associated with primary resistance to standard R-CHOP therapy. Epigenetic sensitization using hypomethylating agents may enhance chemosensitivity in this setting. We prospectively evaluated the clinical activity and safety of a molecularly adapted DAC-R-CHOP regimen in newly diagnosed A53-DLBCL. Methods: In this single-center prospective pilot cohort study, 70 consecutive patients with newly diagnosed DLBCL underwent targeted next-generation sequencing using a 60-gene panel with integrated copy number variation analysis. Six patients (8.5%) were classified as the A53 subtype. All patients received one cycle of standard R-CHOP. From cycle 2 onward, A53 patients received decitabine (10 mg/m² IV, days 1–5) prior to R-CHOP (DAC-R-CHOP), for a total of six cycles. The primary endpoint was complete metabolic response (CMR) according to Lugano 2014 criteria. Exact 95% confidence intervals (CI) were calculated. Results: The median age of the A53 cohort was 65 years. CMR was achieved in all six patients (100%; 95% CI, 54–100%). At a median follow-up of 6 months, all patients remained alive in confirmed CMR. Grade III–IV hematologic toxicity occurred in all cases. Febrile neutropenia developed in 100% of patients, requiring mandatory G-CSF support and anti-infective therapy; no treatment-related mortality or permanent dose reductions were observed. Two patients (33%) experienced gastrointestinal bleeding related to local tumor lysis, which was managed conservatively without protocol discontinuation. Conclusions: In this prospective molecularly stratified pilot cohort, integration of decitabine into front-line immunochemotherapy showed promising clinical activity in A53-DLBCL, albeit at the cost of substantial hematologic toxicity requiring intensive supportive care. Given the small sample size, short follow-up, and absence of a comparator arm, these findings should be considered hypothesis-generating and warrant validation in larger multicenter phase II studies with integrated translational biomarker analyses. Full article

Background: Resistant hypertension poses a significant therapeutic challenge, often leading to severe polypharmacy. Renal denervation (RDN) has re-emerged as a valuable adjunctive intervention for blood pressure control. Case Presentation: We report the case of a 64-year-old man (body mass index [BMI] 34 kg/m²) with long-standing resistant hypertension (RH), after previous percutaneous coronary intervention (PCI) to the left anterior descending artery, heart failure with preserved ejection fraction (HFpEF), and prior nephron-sparing surgery for clear cell renal carcinoma. Despite treatment with an extensive antihypertensive regimen encompassing nine pharmacological classes including diuretic therapy (angiotensin-converting enzyme inhibitor; calcium channel blocker, thiazide diuretic, β-blocker, α1-blocker, central α2-agonist, mineralocorticoid receptor antagonist, loop diuretic, long-acting nitrates), blood pressure remained severely uncontrolled on both home and office measurements. Persistent hypertension was accompanied by exertional dyspnoea and episodes of exertional chest discomfort. Following comprehensive evaluation and exclusion of secondary causes of hypertension, the patient underwent catheter-based renal denervation using the SymplicitySpyral™ (Medtronic) multi-electrode radiofrequency system. The procedure was associated with substantial and sustained improvement in blood pressure control, with mean 24 h ambulatory blood pressure measurements decreasing to 130/80 mmHg at six-month follow-up. Importantly, successful blood pressure reduction enabled major simplification of pharmacotherapy, including complete discontinuation of clonidine, loop diuretic therapy, and long-acting nitrates, together with marked dose reduction in doxazosin. Conclusions: This case illustrates the potential clinical utility of renal denervation in carefully selected patients with true resistant hypertension and pronounced sympathetic overactivity. Beyond achieving satisfactory blood pressure control, RDN may facilitate meaningful reduction in medication burden, potentially improving treatment adherence, quality of life, and long-term cardiovascular risk. Written informed consent was obtained from the patient for both the procedure and the publication of this case report. Full article

Background: Acute angle-closure glaucoma (AACG) is an emergency requiring rapid intervention to prevent irreversible optic nerve damage and permanent vision loss. Methods: This narrative review synthesizes the systemic medication classes most implicated in medication-induced AACG, outlining their underlying pathophysiological mechanisms, typical timing of onset, and practical risk-reduction strategies. Evidence was collected through targeted searches of the PubMed, Google Scholar, Cochrane Library, and Web of Science databases, focusing on major review articles, pharmacoepidemiologic studies, and clinical consensus guidelines. Source selection and data synthesis followed a narrative approach without formal risk of bias assessment or meta-analysis. Results: The literature consistently implicates sulfonamide derivatives (mainly topiramate), serotonergic antidepressants and triptans, potent systemic anticholinergics, and adrenergic decongestants. Sulfonamides typically precipitate bilateral, non-pupillary-block AACG via ciliochoroidal effusion, secondary anterior displacement of the lens-iris diaphragm, and an acute myopic shift. Conversely, serotonergic, anticholinergic, and adrenergic agents typically trigger classic pupillary-block AACG in anatomically predisposed eyes with pre-existing narrow angles. Adverse events predominantly occur shortly after treatment initiation or dose escalation. Management relies on prompt medication discontinuation and rapid intraocular pressure reduction. Importantly, cycloplegics are preferred over miotics in effusion-induced cases. Given the rarity of these events, brief patient education represents a pragmatic and scalable approach, although its direct clinical effectiveness in reducing event rates has not yet been formally established. Conclusions: A select group of widely prescribed systemic medications are associated with most cases of medication-induced AACG. Improving clinician awareness, providing brief patient counseling on warning symptoms, and ensuring prompt ophthalmic evaluation represent the most practical currently available risk-reduction strategies to prevent vision loss. Full article

Background: Tuberculosis remains a major public health challenge in Latin America, where social inequalities, fragmented health systems, and barriers to care continue to undermine disease control. Although effective treatment is available, treatment abandonment and loss to follow-up remain persistent obstacles to successful outcomes. Methods: A structured critical analysis of the contemporary literature on tuberculosis treatment abandonment and retention in care was conducted using a narrative evidence synthesis approach. Forty scientific documents published between 2018 and 2026 were included. Of these, 23 Latin American studies informed the results synthesis, while 13 international studies supported the comparative critical reflection. Results: Findings were organised into five domains: social vulnerability, clinical complexity, health system barriers, priority populations, and protective factors and innovation. The evidence indicates that treatment abandonment is not an isolated individual behaviour, but a phenomenon associated with the convergence of social, clinical, and institutional determinants across the care trajectory. Poverty, migration, drug resistance, incarceration, weak follow-up systems, and fragmented care were repeatedly associated with discontinuity, whereas social support, active follow-up, digital tools, and economic measures were linked to improved adherence and retention in care. Conclusions: From a biopsychosocial perspective, treatment abandonment should be understood as a systemic and preventable failure across the tuberculosis care continuum. The proposed Latin American Integrated Model for Retention in Tuberculosis Care (MILERTB) offers an anticipatory, equity-oriented, and person-centred framework to strengthen retention in care and guide future implementation research. Full article

Gastrointestinal (GI) adverse drug reactions (ADRs) are common among glucagon-like peptide-1 receptor agonist (GLP-1 RA) users and frequently contribute to treatment discontinuation and reduced therapeutic benefit. This retrospective study aimed to develop and validate an explainable artificial intelligence (XAI) model to predict GI ADR risk among GLP-1 RA users using real-world clinical data from the NIH All of Us Research Program. Adults prescribed GLP-1 RAs were identified and classified according to the occurrence of GI ADRs following treatment initiation. Multiple supervised machine learning models, including logistic regression, random forest, extreme gradient boosting (XGBoost), support vector machine, neural network, LightGBM, and CatBoost, were evaluated using demographic, socioeconomic, clinical, medication, and laboratory variables. Model performance was assessed using area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1-score. A total of 8697 participants were included, of whom 59.1% experienced GI ADRs. All models demonstrated reasonable predictive performance, with AUC values ranging from 0.82 to 0.84. The XGBoost achieved discrimination of (AUC: 0.84 ± 0.01). SHapley Additive exPlanations (SHAP) identified gastroesophageal reflux disease, hemorrhoids, and elevated HbA1c as important predictors of GI ADR risk. These findings demonstrate the potential utility of explainable machine learning approaches for predicting the safety of GLP-1 RA therapy. Full article

Background/Objectives: Among the most common medical conditions of pregnancy, nausea and vomiting of pregnancy (NVP) and its severe form hyperemesis gravidarum (HG) represent a clinically significant and increasingly researched area of maternal health. However, the global evolution, structural organization, and thematic development of this literature remain insufficiently characterized. This bibliometric study maps five decades of global research on therapeutic and supportive interventions for NVP and HG. Methods: Web of Science Core Collection records were searched on 10 May 2026, restricted to English-language articles and reviews published up to 2025, and deduplicated to 1182 unique documents. A secondary thematic filter was subsequently applied to generate a refined obstetric subset for the country collaboration, keyword co-occurrence, and thematic evolution analyses. Bibliometric performance, collaboration networks, source impact, institutional output, PELT-based changepoint detection, metadata completeness, keyword co-occurrence, and thematic evolution were analyzed using VOSviewer, Bibliometrix/Biblioshiny, and custom Python scripts. Results: Publication output increased markedly after 2010 and reached its maximum in 2025. PELT sensitivity analysis localized the principal transitions to the mid-1990s and early 2010s, informing three broad analytical macroperiods: 1975–1994, 1995–2009, and 2010–2025. The United States dominated cumulative output and collaboration intensity, while Canada, England, Australia, Italy, Germany, and China showed substantial scientific influence. Core publication venues were concentrated in obstetrics, gynecology, reproductive safety, and pregnancy-focused clinical medicine. Keyword and thematic analyses showed a transition from early vomiting, Bendectin, exposure, and pregnancy-safety concerns toward pharmacological treatment, complementary interventions, controlled clinical evaluation, maternal–fetal outcomes, and supportive management. Metadata-completeness analysis identified a major pre-1991 indexing discontinuity, requiring caution when interpreting long-range keyword-based trends. Conclusions: These findings outline the trajectory of the field and highlight priorities for future research, including stronger comparative evidence for pharmacological, complementary, and supportive-care strategies, broader international collaboration, and prospective studies to strengthen the evidence base for managing NVP and HG. Full article

Fused filament fabrication (FFF) is one of the most widely adopted additive manufacturing methods for thermoplastic polyurethane (TPU)-based soft pneumatic actuators, enabling low-cost fabrication, geometric customization, embedded pneumatic architectures, and rapid prototyping for soft robotic systems. However, despite these advantages, achieving reliable airtightness remains a major challenge due to process-induced anisotropy, interlayer voids, incomplete filament fusion, residual porosity, seam discontinuities, material permeability, and interface-related leakage. These defects can significantly reduce pressure retention, actuation efficiency, deformation repeatability, and long-term pneumatic reliability. This review systematically examines the dominant leakage mechanisms affecting FFF-printed soft pneumatic actuators and comparatively analyzes fabrication approaches, TPU material systems, geometric design factors, post-processing methods, sealing strategies, and leakage characterization techniques. Representative experimental observations, including pressure-decay testing, submerged-bubble visualization, microscopy, and localized thermal surface treatment, are also discussed to connect the findings reported in the literature with experimentally observed leakage behavior. Emerging analytical leakage models, sensing technologies, AI-assisted predictive monitoring, and digital-twin-enabled manufacturing frameworks are reviewed as promising approaches for developing leakage-aware soft robotic systems. The review highlights current limitations related to standardized leakage testing, cyclic durability evaluation, scalable sealing strategies, and intelligent manufacturing integration. Overall, airtightness is identified as a coupled material-process-geometry challenge that must be systematically addressed to improve the reliability, scalability, and long-term operational stability of next-generation TPU-based soft pneumatic actuators. The review was conducted following the PRISMA-ScR framework and includes 248 studies published between 2017 and 2026. Full article

Dysgeusia is a clinically consequential, but still under-standardized, toxicity of cancer treatment. In the immunotherapy era, taste disturbances are increasingly relevant for patients receiving immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapies and T-cell-redirecting bispecific antibodies, with G protein-coupled receptor family C group 5 member D (GPRC5D)-directed treatment in multiple myeloma representing a particularly instructive high-burden model. We performed a structured critical narrative review with evidence mapping. PubMed/MEDLINE was searched from database inception to June 2026, complemented by citation tracking in Google Scholar, ClinicalTrials.gov searches and guideline documents relevant to oncology nutrition, oral supportive care and cancer-related taste dysfunction. Search concepts covered cancer-related dysgeusia, immunotherapy-associated oral toxicity, GPRC5D/talquetamab-associated dysgeusia, oncology nutrition, oral–gut microbiome biology, natural taste modulators and miraculin-based interventions. Dysgeusia can reduce appetite, food enjoyment, dietary diversity and protein energy intake, thereby contributing to weight loss, malnutrition risk, distress, social withdrawal and, in severe cases, treatment modification or discontinuation. Available evidence is heterogeneous: general cancer-treatment-associated dysgeusia is supported by broader observational and interventional literature; immunotherapy-associated dysgeusia is less systematically characterized; and GPRC5D/talquetamab-associated dysgeusia represents the most clinically visible and target-specific immunotherapy-associated phenotype. Emerging pilot data suggest that dried miracle berry or miraculin-containing products may improve selected taste perception and nutritional parameters in cancer-related dysgeusia, but direct evidence in immunotherapy-associated dysgeusia is not yet established. We, therefore, propose a claim-disciplined precision supportive-care framework integrating systematic taste phenotyping, early nutritional risk assessment, oral health evaluation, microbiome-aware but hypothesis-generating endpoints, individualized flavor and texture adaptation, cautious use of natural taste modulators in selected patients and iterative monitoring of patient-centered outcomes. Future trials should test whether dysgeusia-focused nutritional and taste-modulating supportive care interventions can improve intake, quality of life and treatment persistence without compromising immunotherapy safety or efficacy. Full article

Therapeutic inertia has been extensively examined in chronic medical conditions but remains insufficiently conceptualized and empirically studied in psychiatry. This structured narrative review examines therapeutic inertia as a multilevel and potentially bidirectional phenomenon arising when clinically relevant care is not reconsidered or modified despite unmet therapeutic goals and the availability of a reasonable and feasible alternative. A targeted PubMed search was supplemented by backward and forward citation searching, prioritizing psychiatric evidence and foundational literature on clinical decision-making under uncertainty. The review distinguishes therapeutic inertia from appropriate caution, watchful waiting, informed refusal, structural non-access, therapeutic nihilism, medical futility, therapeutic obstinacy, and evidence-based deprescribing. Potential determinants include cognitive and emotional mechanisms, diagnostic and prognostic uncertainty, adverse-effect concerns, patient preferences and previous experiences, therapeutic relationships, resource constraints, fragmented care, guideline structures, workload, and medicolegal culture. Clozapine underutilization in treatment-resistant schizophrenia represents the most compelling psychiatric example, while direct but more limited evidence is available in major depressive and bipolar disorders; applications to anxiety, obsessive-compulsive, substance-use, and non-pharmacological care remain largely hypothesis-generating. Strategies include explicit therapeutic goals, planned reassessment, measurement-based and guideline-informed care, shared decision-making, multidisciplinary review, improved access, clinical decision support, and audit and feedback. Future research should use operational definitions, experimental and observational designs, patient-centered outcomes, and real-world data to determine when treatment non-modification is inappropriate and whether corrective interventions improve care without promoting indiscriminate escalation, coercion, polypharmacy, or premature discontinuation. Full article

Background: Dual immune checkpoint inhibitor therapy with nivolumab plus relatlimab has substantial clinical activity against metastatic melanoma. The incidence and timing of endocrine immune-related adverse events with this treatment remain poorly characterized. Methods: We conducted a retrospective record review of 52 sequential patients who received nivolumab plus relatlimab as initial therapy for metastatic cutaneous melanoma. All patients underwent sequential endocrine screening (TSH, FT4, ACTH, cortisol) prior to each monthly treatment cycle. The incidence and onset of hypothyroidism and hypopituitarism were evaluated, as was cancer treatment outcome. Results: Biochemical evidence for endocrinopathy was identified in 25% of patients. This included a 13.5% incidence of hypothyroidism (median onset 79.0 ± 63.9 days) and 11.5% incidence of hypopituitarism (median onset 243.5 ± 75.6 days). Due to screening and early replacement therapy, there were no related hospitalizations. Patients who developed endocrinopathy showed a trend toward improved progression-free and overall survival. An exploratory analysis suggested that the incidence of endocrinopathy was significantly lower in patients treated with nivolumab plus relatlimab than in those treated with ipilimumab plus nivolumab. Conclusions: During treatment with nivolumab plus relatlimab, endocrinopathy developed in approximately 25% of metastatic melanoma patients, emphasizing a need for screening testing. In an exploratory analysis, endocrinopathy appeared less frequent than in ipilimumab-plus-nivolumab-treated patients. Recovery from endocrinopathy appeared uncommon. Development of delayed endocrinopathy following elective treatment discontinuation for patients in remission was rare (3.8%). Patients who developed endocrinopathy showed a trend toward improved clinical outcome. Full article

Wave propagation modeling in heterogeneous media requires numerical methods that can simultaneously handle complex geometries, artificial boundary reflections, and spatially varying resolution demands. In this study, we present a Discontinuous Galerkin (DG) forward modeling method for wave propagation with split-field absorbing boundary conditions and gradient-based adaptive meshes. The wave equation is formulated as a first-order hyperbolic system and discretized by the DG method, which preserves local conservation and is well suited for explicit Runge–Kutta time integration on unstructured meshes. To reduce spurious reflections from truncated computational boundaries, a split-field absorbing boundary treatment is introduced in the absorbing layer through directional damping terms, maintaining the first-order structure and local update form of the DG scheme. In addition, a physics-based mesh metric is constructed from the local velocity-gradient length scale, allowing the mesh to be automatically coarsened in smooth regions and refined near strong velocity contrasts, interfaces, and discontinuities. Numerical convergence tests show that the quadratic DG scheme achieves the expected third-order accuracy in the L2 norm. Quantitative PML evaluation gives a reflection coefficient of approximately $1.65\times {10}^{-5}$, indicating effective suppression of artificial boundary reflections. For the three-dimensional Marmousi model, the proposed adaptive mesh reduces the number of tetrahedral elements from 158,492 to 88,681, decreases the CPU time from 241.4453 s to 139.1328 s, and reduces memory consumption from 3788.67 MB to 2109.55 MB compared with the uniform mesh. These results demonstrate that the proposed method can improve the balance between computational efficiency and solution accuracy while maintaining stable and physically interpretable wavefield modeling in heterogeneous media. Full article

Chimeric antigen receptor (CAR) therapies are emerging as promising strategies, particularly for metastatic castration-resistant prostate cancer (PCa), as they can act independently of the androgen receptor axis. Adapter CAR-T cell platforms, such as the RevCAR system, offer precise therapeutic control and tumor targeting via small, rapidly eliminated tumor-specific adapters. To enable more convenient late-stage RevCAR-T therapy in PCa patients, allowing for discontinuous reverse target module (RevTM) infusion, we developed novel, larger IgG4-based RevTMs targeting prostate stem cell antigen (PSCA) and benchmarked them against previously described smaller adapter formats. Within the RevCAR system, PSCA-IgG4 RevTMs effectively mediated PCa killing at low effector-to-target ratios and low RevTM concentrations in a strictly antigen-dependent manner. Oncolytic activity was accompanied by a rapid and pronounced release of proinflammatory cytokines across a broad RevTM concentration range, which is particularly advantageous for immunologically cold PCa. Finally, anti-tumor activity was confirmed in a short-term mouse model. Preliminary PET studies further indicate slow blood elimination and tumor-specific accumulation of novel IgG4-RevTMs. Together, these data position PSCA-IgG4 RevTMs as promising candidates for stepwise RevCAR-T treatment in PCa, in which short-lived scFv-RevTMs are initially used to ensure a rapid safety switch, followed by larger IgG4-RevTMs once the risk profile is known. Full article

Background: Feline hyperthyroidism is the most prevalent endocrine disorder of older cats; TT4 monitoring is costly and often inaccessible. Methods: Forty-three cats with primary hyperthyroidism were followed prospectively at baseline (T0) and at 1, 3 and 6 months (T1, T2, T3). Hct, Hgb, MCV, ALT and TT4 were measured at each visit. Per-timepoint correlations, repeated-measures correlation (rmcorr), linear mixed-effects models, and Friedman and ROC analyses were performed. Results: TT4 correlated with Hct (r = 0.875 at T1 to 0.943 at T3), MCV (0.907 to 0.964), Hgb (0.836 to 0.946) and ALT (0.919 to 0.981), intensifying progressively. Within individual cats, Hct (rmcorr r = 0.873) and MCV (rmcorr r = 0.881) tracked TT4, and for Hct, the within-cat coefficient exceeded the between-cat coefficient. All primary parameters and ALT changed significantly from T0 to T1 (all p < 0.001). ROC analysis identified Hct ≥ 35.2% at T2 as the optimal cut-off (AUC = 0.972, 95% CI 0.914–1.000; sensitivity 96.7%, specificity 92.3%). Conclusions: Hct and MCV tracked TT4 within individual cats during methimazole therapy and returned toward pre-treatment values after discontinuation. A rising Hct or MCV in a treated cat may signal loss of therapeutic control and prompt TT4 re-evaluation, without replacing hormonal monitoring. Full article

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, and lowering low-density lipoprotein cholesterol (LDL-C) remains a cornerstone of cardiovascular prevention. Statins are among the most extensively studied and widely prescribed medications and have demonstrated substantial benefits in reducing major adverse cardiovascular events in both primary and secondary prevention settings. Nevertheless, the effectiveness of statin therapy in routine clinical practice is frequently compromised by poor adherence, treatment discontinuation, concerns regarding adverse effects, and persistent residual cardiovascular risk. This narrative review synthesises contemporary evidence relating to the mechanisms of action of statins, their role in primary and secondary prevention, determinants of medication adherence, statin-associated muscle symptoms (SAMSs), and emerging developments in precision cardiovascular medicine. Current evidence indicates that although statins remain highly effective in reducing cardiovascular risk, long-term treatment success is strongly influenced by behavioural, psychological, social, and healthcare system factors. Increasing attention has also been directed towards the multifactorial nature of SAMSs and the contribution of nocebo effects to perceived statin intolerance. Emerging approaches involving pharmacogenomics, artificial intelligence, digital health technologies, and multidimensional risk assessment offer opportunities for more individualised prevention strategies, although important limitations relating to cost, accessibility, and external validity remain. Overall, contemporary cardiovascular prevention requires a patient-centred approach that integrates biological, behavioural, and social determinants of health to optimise treatment adherence and improve long-term cardiovascular outcomes. Full article