BACKGROUND The clinical outcomes of endoscopic rubber band ligation (ERBL), injection sclerotherapy (IS), and endoscopic polidocanol sclerobanding (ESB) have not yet been well studied. AIM To evaluate the efficacy and safety of ERBL, IS, and ESB for treating grade I-III internal hemorrhoids. METHODS This retrospective cohort study was performed on 201 patients, who were grouped according to their endoscopic treatment (ERBL, IS, and ESB groups). Postoperative follow-ups were initially carried out at 1, 3, and 6 months, and then every 6 months, with the longest follow-up extending to 24 months. The study analyzed clinical efficacy, short-term and overall recurrence rates, and postoperative adverse events. Additionally, subgroup analysis was conducted based on the internal hemorrhoid grade (I or II-III). RESULTS The patient distribution across the ERBL, IS, and ESB groups was 70, 66, and 65, respectively. Both the ERBL and ESB groups demonstrated lower overall recurrence rates compared with the IS group (post-hoc analysis, P ’ = 0.024 and P ’ = 0.015, respectively). Subgroup analysis revealed that sclerotherapy resulted in a higher total recurrence rate than that achieved by sclerobanding (45.95% vs 19.57%, P ’ = 0.03), specifically for grade II-III internal hemorrhoids. No significant difference was found in grade I hemorrhoids. The ERBL group exhibited a higher incidence of postoperative pain, a worse median visual analog scale score, and a longer median duration of pain compared with those reported by the other groups (P < 0.001). This trend was consistent for grade II-III hemorrhoids. No significant differences were found among the three groups regarding clinical efficacy or recurrence rates within 6 months post-surgery, even when examined by subgroup. CONCLUSION The three treatments evaluated (ERBL, IS, and ESB) provide durable clinical outcomes for grade I hemorrhoids, with no significant differences in postoperative adverse events. For grade II-III hemorrhoids, ESB possesses the dual advantages of lower recurrence rates and reduced postoperative pain compared with IS and ERBL.

Advancements in monitoring adverse events following immunization in Iraq: Insights from the CIVIE project 2022-2023.

Objective: To evaluate the safety and immunogenicity of a live attenuated varicella vaccine and to explore factors influencing post-vaccination varicella-zoster virus (VZV) antibody levels in healthy children aged 1-6 years in Zhejiang Province. Methods: A total of 378 healthy children aged 1-6 years were enrolled from Quzhou and Lishui in Zhejiang Province and categorized into three groups: 1-3-year-olds without prior vaccination, 4-6-year-olds without prior vaccination, and 4-6-year-olds with one prior dose of vaccination. All participants received one dose of live attenuated varicella vaccine. Serum samples were collected before and 30-35 days after vaccination, and VZV-IgG antibodies were detected using the fluorescent antibody to membrane antigen (FAMA) assay. The incidence of adverse events (AEs) within 30 days post-vaccination was assessed. Geometric mean titers (GMT), seroconversion rates (SCR), and seropositive rates (SPR) of VZV-IgG antibodies were analyzed before and after vaccination. The multiple linear stepwise regression was used to explore factors influencing post-vaccination GMT. Results: All 378 enrolled participants completed vaccination. The overall incidence of AEs was 6.61%, with no significant difference between the primary and booster immunization groups in 4-6-year-olds (6.67% vs. 6.77%, χ2<0.001, P>0.999). Among 355 participants included in the immunogenicity analysis, the pre-vaccination SPR in the 4-6-year-old group with a vaccination history was only 18.64%. The overall SCR after vaccination in children aged 1-6 years was 87.04%, and the overall GMT was 23.14, with GMTs of 22.04, 15.81, and 27.15 in the unvaccinated 1-3-year-olds, unvaccinated 4-6-year-olds, and previously vaccinated 4-6-year-olds, respectively. Multiple linear stepwise regression revealed that pre-vaccination antibody titer (standardized β=0.58, P<0.001) and prior varicella vaccination history (1 dose vs. 0 dose: standardized β=0.11, P=0.011) were positively associated with post-vaccination antibody titer. Focusing on the 4-6-year-old booster group, regression analysis indicated that post-vaccination antibody titer was positively associated with pre-vaccination antibody titer (standardized β=0.60, P<0.001), and participants from Liandu District had higher antibody titers than those from Jiangshan City (standardized β=0.16, P=0.007). Conclusion: The varicella vaccine (human diploid cell SV-1 strain) demonstrates favorable safety and immunogenicity in children aged 1-6 years. Serological evidence indicates a relatively rapid decline in VZV-IgG antibody levels after a single dose, highlighting the need for timely administration of a booster immunization.

Bronchial challenge testing with methacholine was applied to evaluate and quantify bronchial hyperresponsiveness (BHR) in asthma patients. We aimed to compare the clinical effectiveness between methacholine chloride and methacholine for methacholine challenge testing (MCT) in clinical practice, and investigate the adverse events associated with methacholine chloride. Patients who received methacholine and inhaled methacholine chloride for MCT were included in this retrospective study. All participants completed pulmonary function tests and MCT between January 2022 and February 2024. The provocative dose of methacholine that results in a 20% fall in FEV1 (PD20-FEV1) was used as quantitative measure of bronchial hyperresponsiveness. The primary outcome of the study was the proportion of positive MCT results and the degree of BHR, while the secondary outcome was the incidence rate of respiratory adverse events during methacholine chloride administration. A total of 17,352 participants were included. In patients with bronchial symptoms, those administrated methacholine chloride for MCT demonstrated a significantly higher percentage of positive results compared with those administrated conventional methacholine (36.7% vs. 30.8%, P < 0.001). Moreover, PD20-FEV1 values were significantly lower in methacholine chloride group than methacholine group (P < 0.001). Chest tightness was the most prevalent adverse symptom affecting 30.8% of patients who received methacholine chloride, followed by cough at 27.2%. No serious adverse events were reported in these patients. The data indicated that methacholine chloride yielded a higher positive test rate than methacholine in MCT. Given that only mild adverse symptoms of chest tightness and cough were observed, with no serious adverse events reported, it represents a safe and effective alternative for clinical BHR assessment.

Introduction JAK inhibitors are well-established for their utilization in the treatment of autoinflammatory diseases, with the JAK1 inhibitor abrocitinib primarily employed in the management of atopic dermatitis. To provide new clinical therapeutic experience for patients with chronic actinic dermatitis (CAD), reveal the inflammatory pathways that may be involved in the treatment of CAD with abrocitinib and to provide clues for exploring the pathogenesis of CAD. Methods In a 3-month longitudinal study, we recorded and analyzed laboratory test data and clinical severity assessments in 16 patients diagnosed with chronic actinic dermatitis treated with abrocitinib. And the plasma samples of 6 patients before and after treatment were analyzed proteomically using Olink inflammation panel. Results After 12 weeks of treatment, there was a significant decrease in disease severity scores of 16 patients. No serious adverse events were identified throughout the course of treatment. Significant changes in several inflammatory factors such as EN-RAGE, MCP-3, MCP-4, IL-13, CCL4, FGF21 and TNFRSF9 were observed after treatment. Discussion The analysis of our data demonstrates that abrocitinib may be an effective therapeutic option in the management of CAD. IL-13 and CCL-4 might be the core effective factors after the therapy.

The use of high-flow oxygen therapy (HFOT) compared with standard low-flow oxygen therapy (LFOT) may improve outcomes in people with oxygen-dependent chronic respiratory failure (CRF). The primary aim of this multicentre trial was to evaluate HFOT in addition to LFOT, compared with regular LFOT in people with CRF due to chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD). Registry-based randomised controlled trial (R-RCT) of people on LFOT for CRF due to COPD (n = 270) and ILD (n = 40), at ten Swedish secondary care centres within the Swedish Register for Respiratory Failure (Swedevox). People with ongoing LFOT are randomised in a 1:1 ratio to standard treatment with LFOT (control) or LFOT with added HFOT during nighttime and at the patient's discretion daytime (intervention). HFOT is provided using the ResMed Lumis HFT system and the AcuCare HFNC Cannula. Primary outcome is time to first hospitalisation or death up to 1 year in people with COPD. Secondary outcomes include symptoms, health-related outcomes (HRQL), health-economics, adverse events, and to explore the effects of HFOT in people with CRF due to ILD. Outcome data will be obtained from national registries and from patient questionnaires at 3 and 12months. This R-RCT will combine the advantages of a prospective randomised trial and large clinical national registries to improve the evidence-based use of long-term oxygen therapy. Recruitment started in June 2024 and is ongoing. ClinicalTrials.gov, ID: NCT06247397. Registered 2024-02-07.

The optimal conversion treatment for patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer (BRPC/LAPC) remains unclear. In this study, we present the efficacy and safety results of a phase II trial evaluating tislelizumab combined with hypofractionated radiotherapy plus nab-paclitaxel/gemcitabine (THAG) in patients with BRPC/LAPC (ChiCTR2000032955, NCT05634564). This phase II trial enrolled 56 patients with BRPC/LAPC (BRPC: 17, 30.4%; LAPC: 39, 69.6%). Participants received tislelizumab plus nab-paclitaxel/gemcitabine (AG) in 21-day cycles. Nonprogressing patients received concurrent radiotherapy during the third chemotherapy cycle. After four treatment cycles, a multidisciplinary team assessed eligibility for radical surgery. Dynamic biomolecular profiling was performed. Fifty-six eligible patients were enrolled. The objective response rate was 51.8% [95% confidence interval (CI), 38.0%-65.3%]. Median progression-free survival (mPFS) was 13.2 months (95% CI, 11.6-19.4 months), and median overall survival (mOS) was 21.3 months [95% CI, 18.8-not reached (NR)]. Among 30 patients who met criteria for surgical resectability, 22 patients (22/56, 39.3%) underwent radical resection, comprising nine patients with BRPC (9/17, 52.9%) and 13 patients with LAPC (13/39, 33.3%). The margin-negative resection rate reached 90.9% (95% CI, 70.8%-98.9%), and the mOS of patients who underwent surgery was 34.0 months (95% CI, 20.1-NR). Grade ≥3 adverse events (AE) occurred in 33/56 patients (58.9%). Dynamic biomarker exploration revealed that baseline IL6 level (>5 pg/mL) predicted better PFS. Moreover, circulating tumor DNA (ctDNA) status and clearance demonstrated superior survival. The THAG regimen as preoperative therapy showed encouraging clinical activity with a manageable safety profile. Dynamic biomarker findings reveal potential for guiding precision treatment strategies with THAG.

Xanomeline and trospium chloride (X/T) reduced symptoms and was generally well tolerated in two phase 3, 5-week, randomized, double-blind, placebo-controlled trials in adults with schizophrenia. The authors evaluated the long-term safety, tolerability, and efficacy of X/T in an open-label extension of the two phase 3 trials. EMERGENT-4 was a 52-week open-label extension trial of participants who completed the EMERGENT-2 and EMERGENT-3 acute trials. Between February 2021 and October 2023, 152 participants initiated twice-daily oral doses of xanomeline 50 mg/trospium 20 mg and titrated to a maximum dosage of twice-daily oral xanomeline 125 mg/trospium 30 mg. The primary endpoint was the proportion of participants reporting a treatment-emergent adverse event (TEAE). Efficacy measures included Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions severity scale (CGI-S). A total of 156 (42.6%) of the 366 participants who completed EMERGENT-2 or EMERGENT-3 enrolled in EMERGENT-4; of these 34 (21.8%) enrolled participants completed the 52-week treatment period. Overall, 81 (53.3%) of 152 treated participants experienced at least one TEAE. Consistent with the acute trials, the most common treatment-related adverse events were gastrointestinal disorders (e.g., nausea, vomiting, dyspepsia, dry mouth) that were mild or moderate in intensity and resolved with continued treatment. No new safety or tolerability issues were observed. X/T was not associated with clinically meaningful motor symptoms, hyperprolactinemia, weight gain, or adverse effects on metabolic parameters. X/T was associated with continued symptom improvement over the trial duration. Mean changes in PANSS total score from acute trial baseline to week 52 were -33.8 and -31.3 in the treatment groups receiving X/T and placebo, respectively, in the acute trials. Similar patterns of continued improvement were observed for scores on the CGI-S, PANSS positive subscale, and PANSS negative subscale. Long-term treatment with X/T over 52 weeks was safe, generally well tolerated, and associated with durable symptom improvement in people with schizophrenia.

Nanosecond pulsed field ablation, which offers potential benefits, such as reduced muscle contraction, may enable procedures to be performed under local anesthesia.To evaluate the 12-month safety and efficacy of a novel high-repetition frequency nanosecond pulsed field ablation for treating paroxysmal atrial fibrillation. The prospective, multicenter, single-arm trial SCENA-AF study was conducted across 11 Chinese centers. Symptomatic drug-refractory patients with paroxysmal atrial fibrillation aged 18 to 80 years underwent pulmonary vein isolation using a commercial nanosecond pulsed field ablation system. The primary efficacy end point was freedom from documented atrial fibrillation, atrial flutter, or atrial tachycardia ≥30 seconds from 91 to 365 days postablation without use of class I and III antiarrhythmic drugs. The primary safety end point was freedom from device- or procedure-related death, stroke, transient ischemic attacks, or other major complications during the procedure and 12-month follow-up. Of the 166 enrolled patients who underwent the PFA procedures, 162 completed follow-up. Acute pulmonary vein isolation success was 100% for targeted veins. At 12 months, 88.49% (95% CI, 82.54%-92.50%) met the primary efficacy end point. No device- or procedure-related death, stroke, or transient ischemic attacks occurred. Notably, 92.77% of procedures were performed under local anesthesia and conscious sedation. Procedure-specific serious adverse events occurred in 2.41% of patients and were limited to access-site hematomas or pseudoaneurysms that resolved. No clinical hemolysis signs or symptoms were observed. The novel high-repetition-frequency nanosecond pulsed field ablation demonstrated high 12-month efficacy and a favorable safety profile for paroxysmal atrial fibrillation treatment. The ability to perform most procedures under local anesthesia with conscious sedation, with general anesthesia rarely needed, highlights a potential advantage of this technology. www.clinicaltrials.gov; Unique identifier: NCT06039722.

Anti-vascular endothelial growth factor (anti-VEGF) drugs have limitations in the treatment of neovascular age-related macular degeneration (nAMD). This study aims to evaluate the efficacy and safety of radiotherapy combined with anti-VEGF therapy versus anti-VEGF monotherapy in the treatment of nAMD.Methods: This systematic review and meta-analysis (PROSPERO registration number: CRD420251010811) searched PubMed, Embase, Cochrane, Web of Science, LILACS, ISRCTN registry, and ClinicalTrials.gov up to February 25, 2025. Two radiotherapy modalities were analyzed: epimacular brachytherapy (EBM) and stereotactic radiotherapy (SRT). The primary outcome was the proportion of participants who lost more than 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 12 and 24 months. A total of four studies were included, yielding 7 articles for meta-analysis. For EBM combined with anti-VEGF therapy, compared with anti-VEGF monotherapy, there was a higher risk of losing more than 15 ETDRS letters at 12 months (relative risk [RR] 2.36, 95% confidence interval [CI] 1.49-3.74) and 24 months (RR 2.39, 95% CI 1.68-3.39). The difference in best-corrected visual acuity (BCVA) was 0.10 logarithm of the minimum angle of resolution (logMAR) (95% CI 0.05-0.15) at 12 months and 0.17 logMAR (95% CI 0.13-0.21) at 24 months. For SRT combined with anti-VEGF therapy, there was a greater risk of losing more than 15 ETDRS letters at 24 months (RR 1.75, 95% CI 1.12-2.74) compared with anti-VEGF monotherapy; however, the SRT group required 2.10 fewer ranibizumab injections than the sham-irradiation group (mean difference [MD] -2.10, 95% CI -2.97 to -1.22). Epimacular brachytherapy (EBM) combined with anti-VEGF therapy may worsen patient outcomes and increase the risk of adverse events. In contrast, stereotactic radiotherapy (SRT) combined with anti-VEGF therapy does not improve visual acuity but can reduce the frequency of anti-VEGF injections, potentially alleviating the treatment burden for patients with nAMD.

Autologous stem-cell transplantation is a fundamental therapy for multiple myeloma. Although inpatient chemo-based stem-cell mobilization (SCM) is standard care in Germany, outpatient approaches could ease healthcare constraints. We analyzed 109 myeloma patients undergoing SCM and collection at the University Medical Center Göttingen for safety. We then trained machine learning models to predict adverse events (AEs) requiring hospitalization and to forecast AE onset timing for optimized ward management. In our cohort, 97% achieved successful collection, but 69% experienced severe AEs necessitating hospitalization. Simulations suggest a risk-stratified outpatient protocol could cut bed usage by at least one third without compromising safety. Classification models accurately predicted some AE types (e.g., elevated creatinine, ROC-AUC 1.0), though neutropenic fever remained challenging (ROC-AUC 0.67). Regression models forecast AE onset with a mean error of just over one day. These results outline a data-driven roadmap for safely adopting outpatient SCM and optimizing resource allocation in clinical practice.

Triplet therapy with darolutamide, androgen deprivation therapy, and docetaxel (DOC) has emerged as an intensified treatment option for metastatic castration-sensitive prostate cancer (mCSPC). This study evaluated real-world prostate specific antigen (PSA) responses and adverse events (AEs) associated with triplet therapy, with a focus on age-specific differences. We performed a retrospective cohort study across six academic institutions in Japan between February 2023 and February 2025. A total of 137 patients with mCSPC who received triplet therapy were analyzed. PSA responses and AEs were assessed, including subgroup analyses by age (<75 vs ≥75years). The median age was 71years, and 40 patients (29.2%) were aged ≥75years. Six cycles of DOC were completed at similar rates in patients aged <75years (66.0%) and≥75years (57.5%) (P=.435). The median baseline PSA was 298ng/ml, and 107 patients (78.1%) met the CHAARTED high-volume criteria. At three months, the median [interquartile range] PSA decline was 99.8% [99.0-99.9]; 113 patients (92.6%) achieved a PSA decline >90%, and 35 patients (28.7%) achieved a PSA <0.2ng/ml. During follow-up, the proportion achieving a PSA nadir <0.2ng/ml did not differ significantly between patients aged <75years (63.9%) and≥75years (55.0%) (P=.341). Grade≥3 AEs occurred in 56 patients (40.9%), including febrile neutropenia in 29 patients (21.2%). The incidence of AEs did not differ significantly by age. In this real-world cohort, triplet therapy showed substantial PSA declines and acceptable tolerability, with no significant differences in short-term efficacy or safety between patients aged <75 and≥75years. These findings suggest that chronological age alone should not preclude consideration of triplet therapy in appropriately selected patients.

This study evaluated the pharmacokinetics (PK), safety, and tolerability of TV-44749 in patients with schizophrenia or schizoaffective disorder. TV-44749 is a novel, long-acting, subcutaneous (SC) olanzapine injection designed to leverage the benefits of long-acting injectable treatment, reduce the risk for post-injection delirium/sedation syndrome (PDSS), and maintain the efficacy of olanzapine. In this open-label phase I study, patients completed an oral olanzapine treatment period followed by administration of TV-44749 single doses (SD cohort; 318 mg, 425 mg, or 531 mg) or multiple doses (MD cohort; three consecutive monthly doses of 283 mg or 566 mg). For the SD cohort, the follow-up period was up to 84 days (i.e., day 85) after TV-44749 administration. Patients in the MD cohort received TV-44749 on days 1, 29, and 57 over an 84-day treatment period and were followed until the end of the study. Evaluations included PK, adverse events (AEs), clinical assessments, and injection-site pain. A total of 71 (SD, 42; MD, 29) patients each received ≥ 1 dose of TV-44749. Both cohorts had overall similar baseline characteristics. Following subcutaneous administration, TV-44749 reached clinically relevant plasma concentrations (≥ 10 ng/mL) within 1-2 days, with a maximum observed plasma drug concentration (Cmax) within 11-14 days, followed by a sustained release profile over the dosing period of 1 month. The mean beta half-life values ranged from 5 to 10 days, and the mean apparent terminal half-life range was 11-17 days. The systemic exposure (Cmax and area under the plasma concentration-time curve (AUC)) of olanzapine and its two major metabolites, 10N‑glucuronide and N-desmethyl olanzapine, increased in an approximate dose-proportional manner over the clinically relevant dose range of 283 mg through 566 mg. The relative bioavailability of TV-44749 SD and MD compared with oral olanzapine after single or multiple doses was 112% (90% confidence interval (CI) 97, 129%) and 95% (90% CI 86, 106%), respectively. There were no grade ≥3 adverse events, no serious treatment-related adverse events, no suspected or confirmed post-injection delirium/sedation syndrome events, and no deaths. TV-44749 administration resulted in a sustainedrelease profile and comparable exposure to daily therapeutic doses of oral olanzapine over a monthly dosing interval. The TV-44749 systemic safety profile was consistent with approved oral olanzapine. The local tolerability was acceptable, and there were no PDSS events. These results contributed to the dose selection of TV-44749 in a phase III study evaluating its efficacy and safety in adults with schizophrenia (SOLARIS; NCT05693935).

Although PD-1/PD-L1 inhibitors have revolutionized advanced non-small cell lung cancer (NSCLC) treatment, systemic administration is limited by suboptimal local drug concentrations in tumors and the occurrence of immune-related adverse events (irAEs). This study aimed to evaluate the efficacy and safety of local administration of PD-1 inhibitors via bronchial artery infusion (BAI) for the treatment of NSCLC. This single-center prospective cohort study enrolled a total of 47 patients with advanced NSCLC (stage IIIB-IV) who were EGFR and ALK wild-type and exhibited poor response following 2 to 4 cycles of standard treatment. Patients were divided into BAI (n = 23) and Venous (n = 24) groups based on the route of PD-1 inhibitor administration. Both groups received PD-1 inhibitors combined with platinum-based chemotherapy. Notably, chemotherapy was administered via BAI in both groups, with the only difference being the route of PD-1 inhibitor delivery. The primary endpoints of the study was progression-free survival (PFS), and the secondary endpoints were objective response rates(ORR), disease control rates (DCR), overall survival (OS) and safety. At 6-month follow-up, higher ORR (47.8% vs. 16.7%, P = 0.026) and DCR were observed in the BAI group compared to the Venous group (73.9% vs. 41.6%, P = 0.014). The BAI cohort was associated with longer median PFS (11.1 vs. 6.6 months; HR = 0.372, 95% CI: 0.150-0.919; P = 0.030), with a trend toward improved OS (17.9 vs. 15.2 months, P = 0.085). Multivariable analysis identified BAI administration (HR = 0.372, P = 0.032) and younger age (HR = 2.838, P = 0.039) as independent predictors of prolonged PFS. No grade 3-4 treatment-related adverse events were observed in either group of patients. Immune-related pneumonitis (grade 1-2) occurred in 4.3% of patients in the BAI group and 4.2% in the venous group. Due to the limited sample size, a statistical comparison between groups was not performed. All adverse events were manageable with appropriate supportive treatment. BAI administration of PD-1 inhibitors was associated with improved therapeutic efficacy in advanced NSCLC, yielding longer PFS and higher ORR and DCR compared to the Venous group, without increasing severe toxicity.

Current clinical risk tools in type 1 diabetes do not include left ventricular dysfunction or inflammation, potentially limiting early risk detection. We aimed to evaluate the associations and predictive value of combining echocardiography with inflammatory biomarkers for mortality and major adverse cardiovascular events (MACE). In a prospective cohort of individuals with type 1 diabetes without known cardiovascular disease, we evaluated whether subclinical left ventricular dysfunction, defined by an elevated ratio of early mitral inflow velocity to early diastolic mitral annular velocity (E/e') or impaired global longitudinal strain (GLS), combined with elevated levels of an inflammatory biomarker (interleukin-6 [IL-6], soluble urokinase-plasminogen-activator-receptor [suPAR], or high-sensitivity C-reactive-protein [hsCRP]), was associated with all-cause mortality and MACE. Cox models were adjusted for all 10 variables included in the Steno T1 Risk Engine variables: age, sex, systolic blood pressure, duration of diabetes, HbA1c, low-density lipoprotein, estimated glomerular filtration rate, albuminuria status, smoking, and physical activity. C-statistics and net reclassification improvement were assessed. Among 876 participants (51% male, median age 50 years), 114 deaths occurred over 14.5 years of follow-up. Elevated E/e' combined with IL-6 or suPAR, but not hsCRP, was independently associated with mortality. Compared with individuals with E/e' <8 and non-elevated IL-6, the hazard ratio (HR) for E/e' 8-13 with elevated IL-6 was 2.5 (95% CI 1.4 to 4.6, P < 0.01), and for E/e' ≥13 with elevated IL-6 was 3.4 (1.5-7.6; P < 0.01). Corresponding HRs for suPAR were 2.4 (1.2 to 4.7, P < 0.01) and 3.9 (1.8 to 8.5, P < 0.01). Adding E/e' and an inflammatory biomarker increased the C-statistic from 0.839 (Steno T1 Risk Engine alone) to 0.887 (E/e' and IL6) and 0.868 (E/e' and suPAR). Findings were similar for GLS and with MACE as the outcome. Echocardiography combined with inflammatory biomarkers synergistically identifies individuals with type 1 diabetes, without known cardiovascular disease, who are at high risk of mortality and MACE.

Psoriasis and psoriatic arthritis (PsA) are chronic inflammatory diseases, affecting patients' quality of life, particularly when involving difficult-to-treat areas. While randomized controlled trials (RCTs) have shown that ixekizumab is effective for psoriatic disease, real-world evidence (RWE) is essential for assessing its broader applicability. This retrospective, single-center study evaluated the effectiveness and safety of ixekizumab in 37 Greek patients with psoriasis and/or PsA, including involvement of difficult-to-treat areas, over 52 weeks of treatment. Ixekizumab led to significant and sustained improvements in skin disease up to week 52. Joint manifestations and difficult sites showed marked improvement, as did patient-reported quality of life. Biologic-naïve patients and those with early disease onset showed better responses. No serious adverse events were reported, and cardiovascular parameters remained stable. These findings support ixekizumab's strong efficacy and safety in routine clinical use, including patients with prior biologic exposure and complex disease, reinforcing its role as a cornerstone therapy.

To describe a biopsy procedure to obtain subcutaneous adipose tissue (SAT) samples for fibrosis assessment in patients with adipose-based chronic disease (ABCD) and to explore potential associations between SAT fibrosis and comorbidities. Single-center, cross-sectional study conducted at the Arnau de Vilanova University Hospital (Lleida, Spain) between January and December 2024. We included patients aged 18-65 years attending their first appointment in the Obesity Unit. Between-group comparisons were performed using Student's t-test for continuous variables and chi-square tests for categorical variables, and correlations were assessed using Spearman's rank correlation coefficient. 58 patients were recruited and 50 were included in the final analysis. Most were female (76.0%), with a mean age of 47.1 years (SD: 10.8), and a mean BMI of 46.3 kg/m2 (SD: 5.0). The biopsy technique evolved over time, reducing the procedure duration from 55 minutes to under 10 minutes without any adverse events. SAT fibrosis was observed in 10 patients (20.0%), who showed a higher prevalence of type 2 diabetes (50.0% vs. 15.0%, P=0.017), significantly higher aspartate transaminase and gamma-glutamyl transferase, and elevated signs of liver fibrosis. SAT fibrosis was associated with ABCD comorbidities and could serve as a tool for risk stratification beyond traditional indicators.

Viral suppression and adverse events following antiretroviral therapy optimization among children and adolescents in Uganda, 2018-2023.

Objective: Surgical Site Infections (SSIs) are a serious complication in orthopedic surgery, While isotonic saline has long been considered the gold standard for wound irrigation, the current rate of SSIs and the recent saline shortage in 2024 have prompted consideration for using other types of wound irrigation. Vashe Wound Solution (Urgo Medical, Fort Worth, TX, USA) is a pure hypochlorous acid solution that kills bacteria and biofilms by disrupting cell membranes. However, Vashe, in its current commercial product, is not terminally sterilized and there is concern that there is an increased risk of infection. It was hypothesized that Vashe is not inferior to isotonic saline in orthopedic surgery. Methods: With institutional review board approval, a retrospective chart review was performed to include patients treated by our orthopedic trauma service. The final cohort included 100 patients in the Vashe group and 201 patients in the isotonic saline group. Data collected included patient demographics, type of injury, surgical procedure, the type and amount of solution used for irrigation and postoperative complications. Results: There were no statistically significant differences between the two groups regarding postoperative infection, adverse events or complications. Conclusion: The results of this study demonstrate that the use of Vashe for irrigation in orthopedic surgery is safe and is not inferior to isotonic saline.

Recently, increasing studies have reported that Parkinson's disease (PD) may experience an increased incidence of venous thromboembolic events and complications for patients who undergo surgery. We aimed to explore the actual prevalence and risk factors of venous thromboembolism (VTE) for patients with PD as well as its influence on the operative outcomes. We searched PubMed, Embase, and Cochrane library up to 1 May 2025 for observational studies exploring the risk factors of venous thromboembolic events or comparing the frequency of venous thromboembolic events and complications in PD and non-PD patients. The primary outcomes were the risk factors for and incidence of venous thromboembolic events in patients with PD. The secondary outcome was comparing the complications or adverse events between PD and non-PD patients. Two reviewers screened the titles and abstracts of searched records for qualified reports according to the including and excluding criteria and extracted the data independently. Finally, we totally identified 17 observational studies involving 760380 patients for the present analysis. Our pooled results indicated that when compared to patients without PD, patients with PD had significantly higher incidence of venous thromboembolic events, including VTE (OR 1.35, 95% CI 1.11-1.65), deep vein thrombosis (DVT; OR 1.56, 95% CI 1.24-1.96) and pulmonary embolism (PE; OR 1.54, 95% CI 1.20-1.96), respectively. In addition, when comparing DVT (+) and DVT (-) in patients with PD, female patients with PD had a higher frequency of DVT (OR 2.45, 95% CI 1.47-4.06), patients with lower Barthel index [mean difference (MD) -11.5, 95% CI -20.85-2.15] and those with smaller abdominal circumference (MD -7.13 cm, 95% CI -9.99 to -4.26), respectively. When compared to PD patients without DVT, PD patients with DVT had significantly higher average real variability of systolic blood pressure (MD 3.2mmHg, 95% CI 0.75-5.65), lower heart rate at admission (MD -3.32bpm, 95% CI -6.58 to -0.06), higher D-dimer (MD 2.14µg/mL, 95% CI 1.20-3.08), and longer duration of illness (MD 22.68months, 95% CI 6.77-38.58), respectively. Our pooled analysis also indicated that PD increased complications and adverse events of patients receiving operation. Patients with PD were more prone to venous thromboembolic events and had an increased incidence of intra- and post-operative complications. Though several risk factors of DVT were identified for Parkinson's patients, they need further demonstration with specific researches in the future. Greater vigilance should be exercised to make an informed decision regarding patient care and preferred healthcare setup for patients with PD.