Search Results (1,887)

Background/Objectives: Falls and upper limb injuries (ULI) are prevalent in older adults, yet whether ULI independently predisposes to subsequent falls remains poorly characterized. This nationwide cohort study evaluated the association between ULI and future fall risk using Taiwan’s National Health Insurance Research Database (2011–2019, follow-up through 2020). Methods: Adults aged ≥ 50 years with newly diagnosed ULI—defined as fractures (clavicle, scapula, humerus, radius, ulna, hand), sprains, strains, or open wounds of the shoulder, arm, elbow, forearm, wrist, or hand—were propensity score-matched 1:1 to controls by age, sex, and eight major comorbidities. Fall occurrence was identified by validated ICD codes, and Cox regression estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Results: The cohort included 110,600 participants (mean follow-up 4.4 years). Fall incidence was 2.8 versus 1.6 per 1000 person-years in ULI versus control groups. Patients with ULI had 62% higher fall risk (adjusted HR 1.62, 95% CI: 1.43–1.84, p < 0.001), corresponding to 1.2 additional falls per 1000 person-years. Kaplan–Meier curves showed early divergence sustained throughout follow-up. Conclusions: ULI is independently associated with subsequent fall risk in older adults and may serve as a sentinel marker warranting fall-prevention strategies in clinical practice. Full article

Background: Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) usually coexist and are related to increased morbidity and mortality. Cardiovascular benefits have been demonstrated by drugs such as sodium-glucose cotransporter-2 inhibitors (SGLT2i) and GLP-1 receptor agonists including the dual GIP/GLP-1 receptor agonist tirzepatide (collectively, incretin-based therapies); however, their relative effectiveness in patients with concomitant AF and HFpEF remains undefined. Methods: We conducted a retrospective, propensity score-matched cohort study utilizing the TriNetX Global Collaborative Network. Adults with AF or atrial flutter with a diagnosis of HFpEF who initiated incretin-based therapies (GLP-1 receptor agonists or dual GLP-1/GIP receptor agonists) or SGLT2i were included; index medication was required to be initiated within 30 days of a qualifying AF/HFpEF diagnosis. 1:1 matching was performed based on baseline medications, demographics, and comorbidities. Co-primary outcomes were all-cause mortality, inpatient visits, and emergency department (ED) visits at 1 year. Secondary outcomes included myocardial infarction, ischemic stroke, acute kidney injury, transient ischemic attack, major adverse cardiovascular events (MACE; all-cause mortality/MI/stroke composite), and AF-related procedures. Agent-specific subgroup analyses were performed for semaglutide and tirzepatide separately. Sensitivity analyses were conducted at 6 months and 2 years. Results: 7624 patients were included in each cohort after matching (mean age: 70.8 years; 52% women). At 1 year, incretin-based therapy was associated with lower all-cause mortality (5.3% vs. 7.3%, HR 0.721, 95% CI 0.634–0.820; p < 0.001), fewer inpatient visits (30.0% vs. 37.4%, HR 0.743, 95% CI 0.702–0.787; p < 0.001), and no statistically significant difference in ED visits (27.0% vs. 28.0%; HR 0.946, 95% CI 0.888–1.007; p = 0.081) compared with SGLT2i. Incretin-based therapy was also associated with lower risk of MACE (HR 0.709), acute kidney injury (HR 0.751), myocardial infarction (HR 0.583), catheter ablation (HR 0.685), and electrical cardioversion (HR 0.472). No significant differences were observed in ischemic stroke or transient ischemic attack. These findings were broadly consistent at 6-month and 2-year follow-up, and directionally consistent in agent-specific subgroup analyses of semaglutide and tirzepatide. Conclusions: In this large propensity-matched cohort of patients with AF and HFpEF, initiation of incretin-based therapy (GLP-1 receptor agonists or dual GLP-1/GIP receptor agonists) was associated with lower all-cause mortality, fewer inpatient visits, and reduced cardiovascular events compared with SGLT2i. These findings, while subject to observational limitations, suggest potential benefits of incretin-based therapy in this high-risk population and support the need for prospective comparative trials. Full article

Background/Objectives: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with psychiatric burden, but longitudinal data on incident psychiatric outcomes remain limited. This study aimed to evaluate incident psychiatric disorders in adults with HS compared with matched non-HS controls and to assess sex-specific risk. Methods: We conducted a retrospective propensity score–matched cohort study using the TriNetX Global Collaborative Network. Adults with at least two HS diagnoses and no prior psychiatric diagnosis were compared with non-HS controls with repeated general health examination encounters and no psychiatric history. Time-to-event analyses estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses used a 30-day lag and restriction to the most recent 5-year period. Results: After matching, 37,964 pairs were retained for the primary individual-outcome analysis. Median follow-up was shorter in the HS cohort than in matched controls (844 vs. 1505 days). HS was associated with increased risk of any psychiatric disorder (12.3% vs. 5.8%; HR 3.17, 95% CI 3.01–3.34) and severe psychiatric illness (0.6% vs. 0.1%; HR 6.70, 95% CI 4.77–9.41). Elevated risks were observed for bipolar/manic disorders, personality disorders, substance use disorders, psychotic disorders, suicidal ideation, depression, eating disorders, anxiety, and insomnia/parasomnia. Women had higher hazards of depression and anxiety, whereas men had higher hazards of substance use disorders; insomnia/parasomnia showed a nominal association with higher hazard in men. Conclusions: In this observational EHR-based study, HS was associated with broad incident psychiatric morbidity. These findings support consideration of proactive mental health assessment and integrated dermatologic–psychiatric care in patients with HS. Full article

Background: Carpal tunnel syndrome (CTS) is a common peripheral nerve entrapment disorder with multifactorial etiologies, while fibromyalgia is a chronic centralized pain condition characterized by widespread pain and central sensitization. Although shared mechanisms such as neurogenic inflammation and altered pain processing have been proposed, longitudinal evidence evaluating whether CTS predisposes to subsequent fibromyalgia remains limited. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults aged ≥ 18 years with ≥2 clinical encounters between 2018 and 2023 were included. Patients with CTS formed the exposure cohort, while individuals without CTS undergoing routine health examinations served as controls. Those with prior fibromyalgia, malignancy, or death before index were excluded. One-to-one propensity score matching was performed to balance demographics, body mass index, psychiatric conditions, socioeconomic factors, healthcare utilization, and comorbidities including mood, anxiety, stress-related, and sleep disorders. The primary outcome was incident fibromyalgia. Sensitivity analyses included alternative matching strategies, extended washout periods, stricter exposure definitions, and active comparator analyses using osteoarthritis. Stratified analyses by age and sex were conducted. Associations were estimated using hazard ratios with 95% confidence intervals. Results: After matching, 217,208 patients were included in each cohort. CTS was associated with a significantly increased risk of fibromyalgia (HR 2.709, 95% CI 2.521–2.911). Consistent findings were observed across sensitivity analyses. Compared with osteoarthritis, CTS remained associated with higher fibromyalgia risk (HR 1.331, 95% CI 1.254–1.411). Stratified analyses demonstrated consistent associations across age groups (18–64 years: HR 2.820, 95% CI 2.595–3.065; ≥65 years: HR 2.717, 95% CI 2.337–3.159) and sexes (male: HR 3.018, 95% CI 2.482–3.672; female: HR 2.655, 95% CI 2.457–2.869). Conclusions: CTS was associated with coded fibromyalgia diagnosis in this large real-world cohort, and this association was observed across multiple sensitivity and stratified analyses. These findings should be interpreted as evidence of an epidemiologic association rather than a causal relationship. CTS may serve as a clinical marker for patients who warrant attention to broader pain-related symptoms, while future studies are needed to clarify temporality and underlying mechanisms. Full article

We analyze data indicating that a set of currently marketed FDA/EMA-approved drugs used to treat parkinsonism, extrapyramidal side effects of antipsychotic drugs, or overactive bladder may have the potential to slow the growth of glioblastoma; diffuse midline glioma, H3K27-altered (DMG); and a particular form of DMG growing in the pons of children, diffuse intrinsic pontine glioma (DIPG). These gliomas are typically associated with poor prognosis. Clinical trials evaluating conventional chemotherapeutic drugs have failed to improve DIPG survival. Our analysis of the biochemistry and physiology of DMG and DIPG concludes that neuronal acetylcholinergic agonisms at muscarinic receptors M1 and M3 on primitive oligodendrocyte precursor cells (OPCs) are trophic, growth-stimulating factors in DMG/DIPG growth. A set of muscarinic receptor inhibitors—benztropine, biperiden, and trihexyphenidyl—is used clinically to treat Parkinson’s disease or the parkinsonian side effects from antipsychotic medicines. Another muscarinic inhibitor, oxybutynin, is used to treat overactive bladder. All four drugs may impose dose-related side effects inherent to muscarinic receptor inhibition, such as xerostomia, asthenia, and mild cognitive impairment. We recount the evidence for the inhibition of OPC proliferation and migration mediated by these four M1/M3 inhibitors and report details on the rationale for selecting oxybutynin as the primary candidate for adjuvant therapy in DMG/DIPG. We chose oxybutynin as the first choice to study in DMG and DIPG compared to other antimuscarinic drugs based on its (i) high brain-tissue concentration, (ii) relatively stronger M3 inhibition, (iii) lower side-effect propensity than scopolamine, (iv) wide availability, and (v) the absence of H1 antihistamine or dopaminergic effects. Given the rapidly fatal nature of DMG and DIPG, the potential of oxybutynin for growth slowing may outweigh the associated risks and mild side-effect burdens. Full article

Background/Objectives: Following heart transplantation (HT), a subset of patients will require an early or late permanent pacemaker (PPM). We explored risk factors and outcomes associated with PPM implantation in this population. Methods: Using the United Network for Organ Sharing (UNOS) database, we identified all adult patients undergoing HT from 2013 to 2023 who received a PPM early (prior to discharge) or late (>6 months post transplant). Propensity score matching (PSM) was used for control cohorts was. Primary outcomes included recipient survival at 30 days and 1 and 5 years. Predictors of early and late PPM, as well as post-PPM mortality, were assessed using Cox and logistic regression models. Kaplan–Meier survival curves were compared using a log-rank test. Results: Following PSM, the early PPM cohort included 354 patients, and the late PPM cohort included 554 patients. Early PPM patients showed similar 30-day and 1- and 5-year survival (p = 0.582, 0.421, and 0.2844 respectively) but lower rates of graft failure (1.1% vs. 4%, p = 0.017) and primary graft dysfunction (PGD) (1.7% vs. 4.2%, p = 0.046). Late PPM patients had reduced survival at 30 days and 1 year but not at 5 years (p < 0.001, p = 0.0023, 0.050 respectively). Neither early nor late PPM was independently associated with increased risk of mortality after HT. Donation after Circulatory Death (DCD) organs were associated with a lower risk of early PPM (aOR = 0.409, p = 0.020). Late PPM patients showed higher rates of PGD (2.5% vs. 0.5%, p = 0.007). Conclusions: Early or late PPM is not an independent risk factor for mortality after HT, but differing short-term morbidity and mortality are observed. Full article

Background: Patients with type 2 diabetes mellitus (T2DM) who present with ST-segment elevation myocardial infarction (STEMI) remain at high risk of adverse remodeling after reperfusion. This observational study examined whether pre-admission glucose-lowering therapy class was associated with six-month left ventricular (LV) reverse remodeling and myocardial work recovery. Methods: We analyzed 253 patients with STEMI, baseline LV ejection fraction ≤ 50%, successful primary PCI, and complete baseline and six-month echocardiography. The primary inferential analyses focused on 75 patients with T2DM, grouped according to pre-admission therapy with SGLT-2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, or conventional therapy; non-diabetic patients were retained as a descriptive reference group. Clinical outcome, propensity-score, subgroup, and mediation analyses were considered exploratory because of small subgroup and event counts. Results: SGLT-2 inhibitor and GLP-1 receptor agonist exposure was associated with larger improvements in LVEF, LV volumes, and global work efficiency than DPP-4 inhibitors or conventional therapy. Crude MACE rates were highest in the conventional-therapy group, but event estimates were imprecise and confounded by baseline risk, revascularization status, and discharge therapy. Conclusions: In patients with T2DM recovering from STEMI, pre-admission exposure to SGLT-2 inhibitors and, to a lesser extent, GLP-1 receptor agonists was associated with more favorable structural and myocardial work recovery. These hypothesis-generating findings should be interpreted as associations and require confirmation in adequately powered prospective studies. Full article

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely recommended for the treatment of acute (low) back pain, despite modest effectiveness and well-known safety concerns, particularly in older patients. Pridinol is a centrally acting antispasmodic with a mechanism-oriented approach targeting muscle spasm, a key component of acute back pain. While a previous real-world analysis demonstrated a significantly better tolerability and effectiveness of pridinol compared with NSAIDs, age-dependent effects have not yet been systematically evaluated. Objective: To assess the age dependency of effectiveness, safety, and tolerability of pridinol versus NSAIDs in patients with acute (low) back pain under real-world conditions, based on already available data. Methods: This secondary analysis used propensity score-matched real-world data from the German Pain e-Registry (PROVIDENCE study; EUPAS identifier: 49718). A total of 934 patients with acute (low) back pain treated for four weeks with either pridinol (n = 467) or NSAIDs (n = 467) were stratified by age (<65 vs. ≥65 years). Outcomes included the incidence of adverse drug reactions (ADRs), ADR-related treatment discontinuations, time to ADR occurrence, and clinically meaningful improvement in pain-related disability (≥50% reduction in modified Pain Disability Index). Analyses were performed within and between age strata. Results: Overall, ADRs were reported by 9.0% of pridinol-treated patients and 20.8% of NSAID-treated patients (p < 0.001). In the pridinol cohort, ADR rates were virtually identical in patients <65 and ≥65 years (8.9% vs. 9.2%; p = 0.940). In contrast, NSAID-treated patients showed a pronounced age-related increase in ADR incidence (17.3% vs. 32.1%; p < 0.001). ADR-related treatment discontinuation rates under NSAIDs increased markedly with age (5.9% vs. 21.1%; p < 0.001), whereas rates under pridinol remained low and age independent (3.1% vs. 4.6%; p = 0.447). Gastrointestinal and cardiovascular ADRs were the main contributors to the age-related risk increase under NSAIDs, while corresponding events under pridinol were rare across age groups. Clinically meaningful improvement in pain-related disability was achieved with pridinol/NSAIDs in 91.9/48.0% (<65 years) and 88.1/47.7% (≥65 years; p < 0.001 for both). Conclusions: Age is a major modifier of NSAID-related risk but not of pridinol tolerability in acute (low) back pain. While NSAID-associated ADRs and treatment discontinuations increase substantially in patients aged 65 years or older, pridinol demonstrates a stable, age-independent safety profile combined with significantly better functional outcomes. These findings suggest that, particularly in older patients, mechanism-oriented alternatives such as pridinol may offer a more favorable benefit–risk profile than NSAIDs. Full article

Background/Objectives: Functional vulnerability may identify older adults hospitalized with Crohn’s disease flares who are at increased risk for adverse outcomes, but its prognostic significance in this setting remains incompletely defined. We evaluated the association between administratively defined functional vulnerability, identified using administrative diagnostic codes, and short-term clinical outcomes among adults aged ≥65 years hospitalized with Crohn’s disease flares. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Research Network through February 2026. Functional vulnerability was identified using ICD-10-CM codes for frailty, sarcopenia, cachexia, abnormal weight loss, muscle weakness, gait/mobility abnormalities, or reduced mobility within 12 months before or during the index hospitalization. Patients coded only for nonspecific weakness or fatigue were excluded from the functional vulnerability cohort. Patients underwent 1:1 propensity score matching using demographic, comorbidity, Crohn’s disease-related, medication, nutritional, and laboratory variables. The primary outcome was 30-day all-cause mortality. Results: Among 18,420 eligible patients, 2846 met criteria for functional vulnerability, and 15,574 did not. After matching, 2720 patients remained in each cohort. Functional vulnerability was associated with higher 30-day mortality (RR 1.61, 95% CI 1.21–2.14), 90-day mortality (RR 1.40, 95% CI 1.14–1.72), bowel surgery (RR 1.29, 95% CI 1.07–1.56), sepsis (RR 1.41, 95% CI 1.18–1.68), acute kidney injury (RR 1.26, 95% CI 1.10–1.44), ICU admission (RR 1.32, 95% CI 1.13–1.55), TPN use (RR 1.47, 95% CI 1.20–1.79), and 90-day readmission (RR 1.17, 95% CI 1.07–1.29). Functionally vulnerable patients also had longer hospital stays (8.9 vs. 6.7 days; mean difference 2.2 days, 95% CI 1.9–2.5). Conclusions: Administratively defined functional vulnerability identified through diagnostic coding was associated with worse short-term outcomes among older adults hospitalized with Crohn’s disease flares. Although functional vulnerability is a recognized predictor of adverse outcomes across hospitalized populations broadly, these findings quantify its prognostic significance specifically in Crohn’s disease flare hospitalizations and suggest that functional vulnerability may identify a high-risk geriatric IBD phenotype that could benefit from early multidisciplinary assessment, nutritional optimization, rehabilitation planning, and post-discharge care coordination. Full article

An earthquake lethality model was employed to assess the casualty distribution in Yunnan, Guizhou, and Sichuan provinces, taking into account the ground motion acceleration with different 50-year exceedance probabilities. When the probability is 63%, fatalities are predominantly concentrated in central and south-western Yunnan, as well as central, southern, and western Sichuan. At a 10% probability, the peaks of the casualties are observed in southern, eastern, and central Sichuan. In Yunnan (excluding the northwest and southeast regions), the casualty density exhibits unevenness, whereas Guizhou experiences relatively low casualties (except in the eastern and western mountainous areas). Xichang incurs the most substantial losses, followed by Lancang. Xundian, Songming, and Dongchuan demonstrate a high propensity for fatalities, and the risk is relatively high in the vicinity of the Longjiang and Nujiang faults. If a destructive earthquake occurs near these areas within the next 50 years, the probability of a Level-I emergency response exceeds 10%. When the ground motion acceleration doubles (especially when the exceedance probability drops to 2% in 50 year and 0.1% in a year), the predicted number of casualties remains relatively stable. However, the grid of the casualty population exhibits a higher degree of spatial concentration of casualties, and the disaster-affected area expands. There exists no linear correlation between earthquake-induced fatalities and the ground motion level. When the 50-year exceedance probability decreases from 63% to 10%, the casualty rate may increase by several dozen times. Full article

Background/Objectives: This investigation was performed because corticosteroid injections are commonly used for symptomatic relief in patients with meniscal deficiency, yet their effect on graft survivorship and postoperative outcomes following meniscal allograft transplantation (MAT) remains poorly understood, with limited literature specifically addressing this topic. The aim of this study is to evaluate whether preoperative intra-articular corticosteroid injections (ICS) are associated with reoperation after MAT. Secondary aims included comparing reoperation-free survival, patient-reported outcome measures (PROMs), and patient acceptable symptom state (PASS) achievement. Methods: A retrospective review of 130 adults undergoing meniscal allograft transplantation (MAT) between 2011 and 2023 was performed. Patients with documented corticosteroid injection (CSI) status and ≥2 years of follow-up were included. Exclusion criteria included prior meniscal allograft transplantation, receipt of non-corticosteroid injections (e.g., hyaluronic acid or platelet-rich plasma), concomitant osteotomy procedures, multi-ligament knee reconstruction or inadequate follow-up. Propensity score matching (2:1 no steroid: steroid) based on age, sex, body mass index, fixation technique, operative compartment, and concomitant procedures yielded 54 matched patients (35 no steroid, 19 steroid). The primary outcome was ipsilateral knee reoperation, categorized as major reoperation (revision MAT, anterior cruciate ligament reconstruction, osteochondral allograft transplantation, conversion to total knee arthroplasty, meniscectomy and meniscus repair). Minor reoperations included irrigation and debridement, lysis of adhesions or manipulation under anesthesia, hardware removal, chondroplasty, and synovectomy. Reoperation-free survival was assessed using Kaplan–Meier analysis. PROMs and PASS were compared using adjusted regression models. Statistical significance was set at p < 0.05. Results: Baseline characteristics and follow-up were comparable between groups (7.6 ± 3.5 vs. 6.6 ± 3.2 years; p = 0.30). Overall reoperation occurred in 37.1% of patients in the no-steroid group and 31.6% in the steroid group (p = 0.771). Major reoperation rates were similar (17.1% vs. 15.8%; p = 1.000. There was no significant difference in minor reoperations between groups (20.0% vs. 10.5%; p = 0.468). Kaplan–Meier analysis demonstrated no difference in reoperation-free survival (p = 0.903), with comparable survival at the 1-, 2-, and 5-year time points. No individual subtypes differed significantly between groups. PROMs and PASS achievement were also similar, with no statistically significant differences observed. Conclusions: Preoperative corticosteroid injection was not associated with increased reoperation risk, inferior reoperation-free survival, or worse patient-reported outcomes following meniscal allograft transplantation. However, given the study’s limited power, lack of detailed injection characteristics, and the use of a heterogeneous complication outcome, these findings should be interpreted cautiously, as further investigation is warranted. Full article

Background/Objectives: Preterm (<37 weeks) and very preterm (<32 weeks) infants face considerably higher mortality and morbidity rates than full-term infants. We compared clinical outcomes between small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) preterm infants. Methods: This retrospective cohort study used a prospectively collected database, obtained from 2014 to 2025. Propensity score matching (PSM), multivariate regression, and subgroup analyses of very preterm infants were performed to minimize confounding. Results: Among the 5890 neonatal admissions, 2331 preterm infants met the inclusion criteria. After PSM, 298 SGA and 298 AGA preterm infants were analyzed. Multivariate analysis showed that SGA preterm infants had significantly higher risks of the composite outcome of mortality or major morbidity (adjusted risk ratio [aRR], 1.89; 95% confidence interval [CI], 1.18–3.02), mortality (aRR, 3.53; 95% CI, 1.57–7.95), and mortality or moderate-to-severe bronchopulmonary dysplasia (aRR, 2.13; 95% CI, 1.30–3.48). In the subgroup analysis after PSM, 190 very preterm infants showed similar results, with SGA infants having increased risks of the composite outcome of mortality or major morbidity (aRR, 1.81; 95% CI, 1.02–3.23), mortality (aRR, 3.23; 95% CI, 1.09–9.62), mortality or moderate-to-severe bronchopulmonary dysplasia (aRR, 2.03; 95% CI, 1.10–3.72), and mortality or treated retinopathy of prematurity (aRR, 2.62; 95% CI, 1.03–6.65). Conclusions: SGA status is associated with a higher risk of mortality and major morbidity in preterm and very preterm infants. In resource-limited settings, the focused management of SGA infants is critical to improving short- and long-term outcomes. Full article

Objective: TNFSF13B, which encodes B-cell-activating factor (BAFF) and peptidylarginine deiminase 4 (PADI4), plays crucial roles in the pathogenesis of ANCA-associated vasculitis (AAV). This study investigated the associations of single-nucleotide polymorphisms (SNPs) in TNFSF13B/BAFF and PADI4 genes with AAV susceptibility, clinical phenotypes, and disease activity in a Guangxi Chinese population. Methods: A case–control study included 324 AAV patients and 324 healthy controls. After propensity score matching (201 pairs), genomic DNA was genotyped for TNFSF13B/BAFF rs3759467 (formerly rs386492354) and rs1041569, and PADI4 rs11203366 and rs874881 using multiplex PCR and high-throughput sequencing. Genetic associations were analyzed via logistic regression, subgroup, haplotype, and clinical correlation analyses. For each of the four SNPs separately, machine learning models (logistic regression, SVM, Random Forest, XGBoost) were built and evaluated via 5-fold cross-validation. No formal adjustment for multiple comparisons was applied due to the exploratory nature of this study. Results: For TNFSF13B/BAFF, the rs3759467 C allele was protective (dominant model OR = 0.60, p = 0.011; log-additive OR = 0.71, p = 0.020; CA haplotype OR = 0.71, p = 0.019), while the rs1041569 T allele was a risk factor (dominant model OR = 1.70, p = 0.016). Subgroup analysis revealed stronger protective effects of rs3759467 in females, Han ethnicity, and MPA patients, and stronger risk effects of rs1041569 in Han ethnicity and MPA patients. Haplotype CA was protective (OR = 0.71, p = 0.019), and TT was risk-associated (OR = 1.55, p = 0.017). Both TNFSF13B/BAFF SNPs were associated with rash and hemoptysis incidence (p < 0.05). rs1041569 was also associated with RBC (red blood cell) count and HB (hemoglobin) levels (p < 0.05). For PADI4, rs11203366 and rs874881 showed no association with AAV susceptibility (all p > 0.05). However, their genotypes were associated with disease activity (BVAS, Birmingham Vasculitis Activity Score), RBC count, and HB levels (p < 0.05). Although machine learning was applied to explore predictive patterns, its performance was suboptimal (AUC < 0.6), indicating limited clinical applicability. Accordingly, the primary findings rely on the genetic model analysis, and the machine learning results should not be overinterpreted as clinically actionable. SHAP analysis indicated that risk-associated genotypes contributed most to model predictions. Conclusions:TNFSF13B/BAFF gene polymorphisms rs3759467 and rs1041569 were associated with AAV susceptibility in this Guangxi cohort, influencing clinical manifestations like rash, hemoptysis, and anemia severity. PADI4 polymorphisms rs11203366 and rs874881 are not associated with susceptibility but may correlate with disease activity and hematological parameters. These findings highlight the ethnic and clinical subtype specificity of genetic influences in AAV. Due to the lack of external validation, these findings are exploratory and require replication. Full article

While ovarian cancer screening is not recommended in the general population, attention has shifted to screening women with elevated hereditary risks. Although germline BRCA 1/2 pathogenic variants account for 40% of inherited ovarian cancer risk and family history (FH) remains important, known germline variants alone do not fully explain familial ovarian cancer risk. Whole-exome sequencing (WES) was performed on blood samples taken from 231 individuals, including 39 patients with high-grade serous ovarian cancer (HGSOC) and 192 healthy controls (HCs) stratified by FH. We analyzed pathogenic or likely pathogenic (P/LP) germline variants in cancer-related genes and assessed their association with family cancer history. Additionally, we performed somatic variant comparisons using 1:4 propensity score matching and analyzed clonal hematopoiesis of indeterminate potential (CHIP)-related somatic variants. P/LP germline variants were detected in 56.4% of HGSOC patients, 49.4% of controls with FH, and 33.3% without. The HGSOC group and controls with FH exhibited similar P/LP germline mutation patterns in ovarian cancer-related genes. From CHIP analysis, somatic CHIP mutations were detected in 6.3% of the HGSOC group and 8.5% in HCs. Our findings demonstrate genomic overlap between ovarian cancer patients and FH-positive individuals. Therefore, germline variant screening could be considered to facilitate early diagnosis. Full article

Background/Objectives: Patients with unresectable pancreatic ductal adenocarcinoma (UR-PDAC) are vulnerable to rapid nutritional deterioration. The clinical relevance of short-term nutritional change during the diagnostic-to-treatment interval (DTI) remains unclear. In this study, we evaluated whether a dynamic change in the Geriatric Nutritional Risk Index (ΔGNRI) during the DTI is associated with treatment tolerability, treatment continuity, and survival. Methods: This single-center retrospective study included 120 patients with histologically confirmed UR-PDAC who initiated first-line palliative chemotherapy between January 2016 and April 2024. ΔGNRI was defined as the GNRI immediately before chemotherapy minus the GNRI at the initial visit. ΔGNRI was primarily analyzed as a continuous variable, and an exploratory cut-off value of −6.8 was determined by receiver operating characteristic analysis. One-to-one propensity score matching was performed as a sensitivity analysis. Clinically significant adverse events (AEs) were defined as grade ≥3 AEs or AEs requiring treatment modification, hospitalization, or treatment discontinuation. Results: Patients in the GNRI-decreased group had more frequent clinically significant non-hematologic AEs, including gastrointestinal AEs, higher hospitalization rates due to AEs, and more frequent early treatment discontinuation. ΔGNRI remained independently associated with early treatment discontinuation and failure to transition to second-line therapy in multivariable analyses. Patients in the GNRI-decreased group also had significantly shorter times to treatment failure and overall survival. These findings were consistent in propensity score-matched analyses. Conclusions: Dynamic nutritional decline during the DTI was associated with impaired treatment resilience and poor survival outcomes in UR-PDAC. ΔGNRI may help identify patients with emerging nutritional vulnerability before chemotherapy. Full article