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Comparison of VCV and PCV-VG modes on diaphragmatic function in diabetic patients undergoing laparoscopic colorectal surgery: a prospective randomized controlled study.

BACKGROUND: Diabetic patients are prone to induce diaphragmatic weakness, which can lead to postoperative pulmonary complications (PPCs). The optimal mechanical ventilation mode may potentially improve postoperative diaphragmatic function. This study evaluates the effects of two ventilation modes under driving pressure-guided ventilation strategy on diaphragmatic function, as assessed by diaphragm thickening fraction (DTF) and diaphragm excursion (DE), in diabetic patients following laparoscopic colorectal surgery. METHODS: Eighty patients diagnosed with Type II diabetes scheduled for elective laparoscopic colorectal surgery, were randomly allocated to either the pressure-controlled volume-guaranteed ventilation (PCV-VG) group (Group P) or the volume-controlled ventilation (VCV) group (Group V) during surgery. The primary outcome was diaphragmatic function assessed during both tidal breathing and maximal inspiratory effort after surgery. Secondary outcomes included intraoperative mechanical power, PPCs, and other complications. RESULTS: A total of eighty patients were included in the final analysis. The averaged area under the curve (AUC) for mechanical power during ventilation was significantly lower in Group P than in Group V (p = 0.002). PCV-VG significantly improved both DE and DTF within the first two days post-surgery (AUCDEtidal: p = 0.088, AUCDTFtidal: p = 0.004, AUCDEmax: p = 0.029, AUCDTFmax: p = 0.017). Postoperative diaphragmatic weakness was less frequent in Group P than in Group V (p = 0.019). However, there was no difference in the incidence of PPCs between the two groups (p = 0.155). CONCLUSION: PCV-VG mode can reduce intraoperative mechanical power, better preserve postoperative diaphragmatic function. However, these improvements did not translate into clinical benefits, as evidenced by the lack of reduction in the incidence of PPCs.

Humans

Clinical and genetic features of Ph-negative myeloproliferative neoplasms with dual-driver gene positivity.

OBJECTIVES: To investigate the clinical laboratory characteristics and gene mutation features of dual-driver gene positivity in patients with Philadelphia chromosome-negative myeloproliferative neoplasm (Ph-negative MPN). METHODS: We conducted a retrospective analysis of clinical data and genetic test results from 203 newly diagnosed patients with Ph-negative MPN. Of these, 194 had single-driver gene positivity and 9 had dual-driver gene positivity. High-throughput sequencing was used to detect mutations in JAK2, CALR, and MPL. Clinical characteristics and gene mutation profiles were compared between the two patient groups. RESULTS: The incidence of dual-driver gene positivity was 4.4% (9/203), with the most common combinations being JAK2 with CALR (4 patients) and JAK2 with MPL (4 patients). Compared with the single-driver group, the dual-driver group had a significantly higher risk of bleeding [4.1% (8/194) vs. 33.3% (3/9), P = 0.008] and a higher proportion of uncommon mutations [3.6% (7/194) vs. 33.3% (3/9), P = 0.006]. No statistically significant differences were observed between the two groups regarding age, thrombosis incidence, splenomegaly, or routine blood test indicators. During follow-up, 1 patient in the dual-driver group died from cerebrovascular disease. No leukaemia transformation or disease-related deaths occurred among the remaining patients. DISCUSSION: The increased bleeding risk in dual-driver patients may be related to a higher proportion of CALR mutations, elevated platelet counts, and higher variant allele frequencies, though these findings require validation in larger cohorts due to the small sample size. The higher prevalence of uncommon mutations suggests a more complex mutational landscape in this subgroup. CONCLUSION: Patients with Ph-negative MPN and dual-driver gene positivity may have a higher risk of bleeding and a more complex gene mutation profile.

Humans

Diabetic macular edema and GLP-1 receptor agonist use: a systematic review and meta-analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type II diabetes and obesity because of their cardiometabolic benefits. However, concerns regarding potential ocular adverse effects, particularly diabetic macular edema (DME), have prompted the need to clarify their retinal safety. METHODS: A systematic review and meta-analysis study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements (PROSPERO registration: CRD420251176164). MEDLINE (Ovid), EMBASE (Ovid), CENTRAL (Ovid), Web of Science, and PubMed were searched from inception to October 24, 2025. Randomized trials and observational cohort or case-control studies, including individuals with diabetes without baseline DME and exposed to GLP-1RAs were eligible. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-I. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation. Random-effects models were used to pool incidence proportions and hazard ratios (HRs). RESULTS: Thirteen retrospective cohort studies (2021-2025) using large real-world databases were included. Across 6 studies, the pooled proportion of incident DME among GLP-1RA users was 0.14 (95% CI: 0.07-0.23; I² = 99.8%). Compared with mixed antihyperglycemic therapies, GLP-1RA use was not associated with increased DME risk (pooled HR: 0.81, 95% CI: 0.52-1.26). GLP-1RAs were associated with a higher relative risk of DME compared with sodium-glucose cotransporter-2 inhibitors (HR: 1.50, 95% CI: 1.17-1.94) but not compared with dipeptidyl peptidase-4 inhibitors (HR: 0.90, 95% CI: 0.69-1.19). Evidence certainty was very low. CONCLUSION: Current low-certainty observational evidence does not support an overall increased risk of DME with GLP-1RA use. Prospective studies are needed to clarify comparative retinal safety.

Humans

Parental son preference in childhood and sex differences in the risk of cardiovascular disease in middle-aged and older adults.

INTRODUCTION: Sex differences in cardiovascular disease (CVD) risk are examined through biological and clinical factors, with less attention to early-life social exposures. This study examined associations of childhood parental son preference with CVD risk, sex differences, and mediation by modifiable risk factors. METHODS: This cohort analysis included China Health and Retirement Longitudinal Study participants aged ≥45 years without baseline CVD. Parental son preference was assessed retrospectively in 2014; incident CVD was self-reported physician-diagnosed heart disease or stroke through 2020. Sampling-weighted, community-clustered Cox models estimated adjusted hazard ratios (aHRs) and 95% CIs. Sex was prespecified as an effect modifier; mediation by 13 risk factors used inverse-odds-ratio weighting. Data were collected from 2011 to 2020 and analyzed from 2025 to 2026. RESULTS: Among 8,079 participants (mean age, 57.5 years; 4,216 women [52.2%]), 1,820 (22.5%) reported parental son preference. Son preference was associated with higher CVD risk overall (aHR 1.23 [95% CI 1.04, 1.46]) and among women (aHR 1.25 [95% CI 1.03, 1.53]); among men, the estimate was 1.16 (95% CI 0.87, 1.56), with limited heterogeneity by sex (ratio of aHRs 1.06 [95% CI 0.72, 1.58]). Among women, risk was concentrated in the highest paternal (aHR 1.47 [95% CI 1.14, 1.90]) and maternal (aHR 1.50 [95% CI 1.12, 1.99]) preference categories. Modifiable risk factors mediated 5.8% (95% CI 1.9%, 9.7%) of the association among women, mainly through socioeconomic and psychosocial factors. CVD risk was highest with both son preference and high risk-factor burden overall (aHR 1.97 [95% CI 1.43, 2.73]) and among women (aHR 2.23 [95% CI 1.61, 3.10]). CONCLUSIONS: Parental son preference was associated with higher incident CVD risk, with the largest estimates in the highest paternal or maternal categories among women. Modifiable risk factors explained a modest proportion, supporting life-course cardiovascular prevention that considers sex-differentiated childhood environments alongside risk-factor modification.

cardiovascular disease

Early and late CTCAE and patient-reported outcomes following lung cancer radiotherapy: A sex-stratified descriptive analysis from the REQUITE cohort.

BACKGROUND: Long-term prospective data on lung cancer patients treated with radiotherapy are limited, restricting understanding of outcomes and sex-specific characteristics. The multicentre REQUITE study provides standardized follow-up data from an international cohort. METHODS: We analysed longitudinal data from 530 lung cancer patients treated with radical radiotherapy (sequential or concurrent chemoradiotherapy, or stereotactic body radiation therapy [SBRT]) between 2014 and 2017 at 16 centres in Europe and the USA. Healthcare professionals prospectively recorded 21 pulmonary, oesophageal, neurological, cardiac, and skin adverse events using CTCAE v4.0. Patient-reported outcomes assessed symptoms, quality-of-life, fatigue, and physical activity. Adverse event incidence was stratified by sex, radiotherapy technique, chemotherapy administration, smoking status, and other clinical factors. RESULTS: At 12 months, 309 patients were evaluable, with 151 having follow-up beyond one year. Pulmonary adverse events were most frequent (40% grade ≥ 2), mainly dyspnoea and cough. Women had higher rates of oesophagitis, and more frequently reported dysphagia, and chest wall pain, while men experienced a higher frequency of cardiac adverse events. Exploratory subgroup analyses identified significant sex-related differences in grade ≥ 3 pulmonary adverse events following SBRT and in overall grade ≥ 2 oesophageal adverse events among patients with clinical stage I-II and those aged >70 years. Patient-reported outcomes showed persistent fatigue and reduced physical activity, particularly in females. Symptom prevalence and severity varied by sex, age, treatment modality, smoking status, and clinical stage. CONCLUSION: The REQUITE-Lung cohort provides prospectively collected real-world data on radiotherapy-related adverse events in lung cancer patients. This study describes patterns of adverse events and patient-reported outcomes according to sex, age, and treatment characteristics. These findings are hypothesis-generating and may support future validation in independent and pooled datasets.

Patient-reported outcomes

The impact of prehabilitation on postoperative outcomes in patients undergoing radical prostatectomy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: Preoperative rehabilitation training can optimize functional reserve before radical prostatectomy (RP), thereby improving postoperative outcomes. However, its effects on urinary incontinence, erectile function, and quality of life (QoL) remain controversial. This study systematically evaluated these outcome measures. METHODS: Data from randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, Embase, and CINAHL databases. The risk of bias was assessed using the RoB-2 tool, and meta-analysis was performed using Stata 18.0 software. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Meta-analyses were conducted using fixed- or random-effects models according to heterogeneity. Outcomes included urinary incontinence incidence, urinary incontinence severity, erectile function, and QoL at different postoperative follow-up time points. RESULTS: 16 randomized controlled trials involving 1,542 participants were included. Prehabilitation significantly reduced the incidence of urinary incontinence at 1 month (OR = 0.58, 95% CI 0.39-0.84) and 6 months (OR = 0.52, 95% CI 0.28-0.96) after RP, with a non-significant borderline reduction at 3 months, and no significant benefit at 12 months. No significant improvement was observed in urinary incontinence severity or erectile function at any follow-up time point. Prehabilitation significantly improved QoL within 3 months (SMD = -0.70, 95% CI -1.08 to -0.32) and 6 months (SMD = -0.45, 95% CI -0.74 to -0.16) postoperatively. However, within 12 months, the effect size attenuated, showing only a marginal trend that did not reach statistical significance (SMD = -0.33, 95% CI -0.66 to 0.00). Risk of bias was generally moderate. CONCLUSION: Prehabilitation reduces early incontinence and improves QoL post-RP, but its effects on severity and erectile function remain unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [CRD420251183407].

Humans

Sex Differences in Postoperative Recovery and Mortality After High-Risk Cardiac Surgery: A Propensity Score-Matched Post Hoc Analysis of the SUSTAIN-CSX Trial.

BACKGROUND: Sex-related differences after cardiac surgery remain controversial because women often present with higher baseline risk and complexity than men. We performed a post hoc propensity score-matched analysis of the SUSTAIN-CSX (Sodium Selenite Administration in Cardiac Surgery) trial to evaluate sex differences in mortality, postoperative complications, and recovery after high-risk cardiac surgery. METHODS: Of 1394 trial participants, 1386 had complete data. Women were matched 1:1 to men using nearest-neighbor propensity score matching based on age and European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), with exact matching on surgical category, yielding 327 female-male pairs. Prespecified sensitivity analyses adjusted for frailty, baseline hemoglobin, renal disease, left ventricular ejection fraction, previous myocardial infarction, preoperative medications, and baseline creatinine. RESULTS: In the primary matched analysis, 180-day survival did not differ between women and men (log-rank P=0.086; unadjusted hazard ratio, 1.80 [95% CI, 0.91-3.55]; P=0.091). In descriptive matched comparisons, women had numerically longer intensive care unit stay (median, 3 days [quartile 1, quartile 3 (Q1, Q3)=1, 6 days] versus 2 days [Q1, Q3=1, 5 days]) and hospital stay (median, 10 days [Q1, Q3=7, 18 days] versus 9 days [Q1, Q3=6, 16 days]; P=0.292), whereas major postoperative complications were similar. In adjusted sensitivity analyses accounting for the matched design and residual imbalance, female sex remained associated with longer intensive care unit stay (adjusted incidence rate ratio [IRR], 1.8 [95% CI, 1.2-2.9]; P=0.009) and hospital stay (adjusted IRR, 1.4 [95% CI, 1.0-1.9]; P=0.031). Mortality sensitivity analyses were model-dependent. CONCLUSIONS: In this propensity score-matched cohort of high-risk cardiac surgery patients, women showed a longer postoperative recovery trajectory in adjusted analyses, whereas mortality findings were sensitive to model specification and should be interpreted cautiously. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002247.

Aged

Oil and gas well development and coccidioidomycosis risk in Kern County, CA, USA: a case-crossover study.

BACKGROUND: Coccidioidomycosis is an emerging fungal disease caused by inhaling Coccidioides spp spores. As spores reside in soil, activities that disturb soil and generate dust can aerosolise and transport the pathogen. The oil and gas industry has been extensively developed in some regions that are endemic for Coccidioides spp and has been associated with dust emissions. Although several adverse health outcomes have previously been associated with oil and gas development, its impact on coccidioidomycosis risk has not been investigated. We aimed to estimate the association between exposure to oil and gas well development (ie, wells in preproduction) and risk of coccidioidomycosis among residents living near new wells. METHODS: In this case-crossover study, we obtained information on reported coccidioidomycosis cases and oil and gas well development between 2007 and 2022 in Kern County, CA, USA. We then compared exposure to preproduction wells within 5 km of each individual's place of residence during both hazard (ie, the 49-139 days before case onset) and control periods using conditional logistic regression. FINDINGS: During the study period, 658 108 (72·4%) of 909 282 of Kern County residents lived within 5 km of at least one preproduction well, and 116 020 (12·8%) lived within 5 km of 23 or more preproduction wells within a single 90-day period. We estimated that the odds of coccidiomycosis incidence were 12·5% (95% CI 5·8-19·6) higher in the 90 days following exposure to at least one preproduction well within 5 km of an individual's place of residence and that the odds of infection increased by 0·7% (0·4-0·9) for each additional preproduction well developed within this distance. INTERPRETATION: These findings support a previously-unrecognised association between the development of oil and gas wells and transmission of coccidioidomycosis, potentially driven by dust generation. Given the prevalence of oil and gas development in the study region, its impact on coccidioidomycosis incidence might be large. FUNDING: National Institutes of Health, National Science Foundation.

Journal Article

Effectiveness of chlorhexidine gluconate-impregnated dressings in preventing central line-associated bloodstream infection in a paediatric intensive care unit: A randomised controlled trial.

OBJECTIVES: To compare the effectiveness and dermatological safety of chlorhexidine gluconate (CHG)-impregnated dressings versus conventional transparent dressings in preventing central line-associated bloodstream infection (CLABSI) in paediatric patients admitted to a PICU. METHODS: A single-blind, randomised controlled trial with a 1:1 allocation ratio was conducted in a tertiary PICU. A total of 250 paediatric patients with a central venous catheter were included (125 per group). Patient characteristics, catheter-related variables, catheter dwell time and skin alterations were recorded. The primary outcome was CLABSI, defined according to CDC/NHSN criteria. Bivariate analyses and multivariable logistic regression were performed, including clinically relevant covariates related to catheter exposure, dressing type, and vaccination status. The trial was registered at ClinicalTrials.gov (NCT07175116). RESULTS: CLABSI incidence was significantly lower in the CHG group compared with the conventional dressing group (2.4% vs. 18.4%; p&#xa0;<&#xa0;0.001). In multivariable analysis, CHG-impregnated dressings were independently associated with reduced CLABSI risk (OR = 0.15; 95% CI: 0.04-0.58). Longer catheter dwell time (OR = 1.13 per day; 95% CI: 1.04-1.22) and absence of complete vaccination (OR = 8.68; 95% CI: 2.48-30.47) were also associated with increased infection risk. Incomplete vaccination showed a similar trend without reaching statistical significance (OR = 6.48; 95% CI: 0.95-44.20). Skin alterations were more frequent in the CHG group (16.8% vs. 11.2%), predominantly in younger infants. CONCLUSIONS: CHG-impregnated dressings were associated with a significant reduction in CLABSI incidence in critically ill paediatric patients, although their use was linked to a modest increase in mild skin reactions. IMPLICATIONS FOR CLINICAL PRACTICE: CHG-impregnated dressings may be considered as part of a multifaceted infection prevention strategy, alongside appropriate catheter management, minimisation of catheter manipulation and proactive skin monitoring, with cautious and individualised use in infants.

Humans

Esketamine vs. sufentanil for quality of recovery after outpatient gynecological surgery: a randomized clinical trial.

BACKGROUND: Perioperative administration of esketamine has been reported to improve early quality of recovery (QoR). However, data on its effects in outpatient surgery are limited. This study aimed to assess the impact of esketamine on QoR in patients undergoing outpatient gynecological procedures. METHODS: In this investigator-initiated, double-blind, randomized clinical trial, patients aged 18-65&#x2009;years scheduled for outpatient gynecological surgery under sedation were allocated to receive esketamine (0.2&#x2009;mg/kg) or sufentanil (0.1&#x2009;&#x3bc;g/kg) combined with propofol (1.5-3&#x2009;mg/kg). The primary outcome was quality of recovery on postoperative day (POD) 1. Secondary outcomes included quality of recovery on POD2, sedation success rate, length of post-anesthesia care unit (PACU) stay, injection pain, postoperative pain, nausea and vomiting, fatigue, patient and clinician satisfaction, sleep quality, and anxiety and depression. RESULTS: A total of 126 patients were randomized, with 63 assigned to the esketamine group and 63 to the sufentanil group. Of these, 125 patients were included in the final analysis (62 in the esketamine group and 63 in the sufentanil group), as one patient lacked follow-up data. The mean (SD) QoR-15 score on POD1 was 137.9 (14.5) in the esketamine group and 137.8 (10.7) in the sufentanil group, with no significant difference between groups (absolute difference, 0.2; 95% CI, -4.2 to 4.6; p&#x2009;=&#x2009;0.93). For secondary outcomes, the esketamine group had a longer PACU stay (median, 28.0 vs. 23.0&#x2009;min; p&#x2009;<&#x2009;0.001), a lower incidence of severe injection pain (22.6% vs. 50.8%; p&#x2009;=&#x2009;0.002), a higher proportion of patients with pain scores &#x2265; 4 at 30&#x2009;min postoperatively (30.6% vs. 6.3%; p&#x2009;=&#x2009;0.001), and higher fatigue scores (median, 3.0 vs. 2.0; p&#x2009;=&#x2009;0.01). Other secondary outcomes did not differ significantly between groups. CONCLUSION: Among patients undergoing sedation for outpatient gynecological procedures, esketamine did not significantly improve quality of recovery on POD1 compared to sufentanil. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2500098466.

Humans

Intensive glycemic control in adults aged 80&#xa0;years and older: A randomized trial evaluating diabetes complications and competing mortality.

AIMS: To evaluate whether intensive glycemic control reduces microvascular or macrovascular events compared with conservative glycemic targets in independently ambulatory adults aged 80&#xa0;years or older with type 2 diabetes. METHODS: We conducted a prospective, randomized, open-label, single-center trial enrolling independently ambulatory adults aged&#xa0;&#x2265;&#xa0;80&#xa0;years with type 2 diabetes. Participants were assigned (1:1) to an intensive glycemic target (HbA1c&#xa0;<&#xa0;7&#xa0;%) or a conservative target (HbA1c&#xa0;<&#xa0;9&#xa0;%) and followed for 5&#xa0;years. Primary outcomes were composite microvascular and macrovascular events. Analyses were done by intention to treat. Cause-specific Cox models and Fine-Gray subdistribution hazard models were used to account for all-cause mortality as a competing event. This trial is registered with ClinicalTrials.gov, NCT00850798. FINDINGS: 206 participants were randomly assigned to intensive (n&#xa0;=&#xa0;102) or conservative (n&#xa0;=&#xa0;104) treatment. At 5&#xa0;years, mean HbA1c was lower in the intensive group than in the conservative group (7&#xb7;42&#xa0;% vs 8&#xb7;21&#xa0;%; p&#xa0;=&#xa0;0&#xb7;005). Intensive therapy did not reduce microvascular events (hazard ratio [HR] 1&#xb7;24, 95&#xa0;% CI 0&#xb7;76-2&#xb7;04) or macrovascular events (HR 1&#xb7;02, 0&#xb7;36-2&#xb7;92). Competing risk analyses showed no reduction in cumulative incidence of vascular outcomes (subdistribution HR approximately 1&#xb7;0 for both). The cumulative incidence of death exceeded that of vascular events, indicating that many participants died before potential glycemic benefits could be realized. Severe hypoglycemia requiring hospitalization was more frequent with intensive therapy (7 vs 1 event). INTERPRETATION: In adults aged 80&#xa0;years or older with type 2 diabetes, intensive glycaemic control improved glycaemic levels but did not reduce vascular events and increased the risk of severe hypoglycaemia. High competing mortality substantially limits the potential long-term benefit of intensive treatment, supporting conservative and individualized glycemic targets in very old adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00850798.

Aged, 80 and over

HSK21542 for Postoperative Analgesia in Gynecological Surgery: A Pooled Post-Hoc Analysis of Two Phase III Randomized Controlled Trials.

BACKGROUND: Effective postoperative pain management in gynecological surgery is challenging because of complex visceral-somatic pain interactions and the adverse effects of conventional analgesics. HSK21542, a novel peripherally restricted kappa-opioid receptor (KOR) agonist that selectively targets visceral pain pathways enriched with KORs, may provide adequate analgesia without systemic adverse events. METHODS: We conducted a pooled post-hoc analysis of data from two phase III, multicenter, triple-blinded, randomized controlled trials (Study 301, HSK21542 vs placebo; Study 303, HSK21542 vs tramadol vs placebo). Eligible patients undergoing elective gynecological surgery were included. The primary outcome was the summed pain-intensity difference over 12 and 24 hours (SPID 12h and SPID 24h ). Secondary outcomes were pain-relief quality (proportion of patients relieved from severe pain with a pain numerical rating score &#x2264; 3 between 0 and 24 hours) and rescue-analgesic requirements (number of doses and time to first rescue analgesic). Adverse events were also assessed. RESULTS: A total of 370 patients were analyzed: 150 received HSK21542, 139 received a placebo, and 81 received tramadol. After inverse probability of treatment weighting (IPTW) adjustment, baseline characteristics were well-balanced across treatment groups (all standardized mean differences [SMD] <0.1; see Table 1 for 95% CIs). HSK21542 produced greater reductions in pain intensity over 12 and 24 hours than placebo (least-squares mean differences -8.1 and -16.3 for SPID 12h and SPID 24h , respectively. Both P < .001) and no statistically significant difference was observed between HSK21542 and tramadol ( P > .05). Significantly more patients in the HSK21542 group were relieved from severe pain at 0 to 12 hours (92.7% vs 82.7%, P < .001) and required fewer rescue doses at 0 to 12 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) and 0 to 24 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) than those in the placebo group, whereas no significant differences with tramadol both in 0 to 12 and 0 to 24 hours. HSK21542 was also associated with significantly lower incidences of nausea (24.7% vs 66.7%) and vomiting (21.3% vs 60.5%) than tramadol. Only one case of dizziness occurred in the tramadol group. CONCLUSIONS: HSK21542 could provide adequate postoperative analgesia with few adverse events in patients undergoing gynecological surgery.

Humans

[Efficacy and safety of thoracic paravertebral block combined with thoracic nerve block for acute herpes zoster neuralgia involving upper thoracic dermatomes in middle-aged and elderly patients].

To investigate the clinical efficacy and safety of ultrasound-guided thoracic paravertebral block (TPVB) combined with pectoral nerve block (Pecs) in the treatment of acute herpetic neuralgia (AHN) involving the upper thoracic segments in middle-aged and elderly patients, a prospective study was conducted. A total of 70 middle-aged and elderly patients with upper thoracic AHN who visited the Department of Pain Medicine at Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, from June to December 2023, were enrolled and randomly divided into a control group and an experimental group using a random number table, with 35 patients in each group. The control group received TPVB once weekly for a total of 3 sessions, while the experimental group received TPVB combined with Pecs block using the same regimen. Outcome measures included the Visual Analogue Scale (VAS) for pain, Pittsburgh Sleep Quality Index (PSQI), 7-item Generalized Anxiety Disorder Scale (GAD-7), 9-item Patient Health Questionnaire (PHQ-9), treatment satisfaction score, incidence of postherpetic neuralgia (PHN), rescue analgesia, and adverse events. Assessments were conducted at 1, 4, 8, and 12 weeks post-treatment, and between-group differences were compared. Ultimately, 33 patients in the experimental group and 31 in the control group completed the follow-up and were included in the final analysis. The results showed that both groups demonstrated significant improvements in VAS scores, PSQI, GAD-7, PHQ-9, and satisfaction scores compared with baseline (all P<0.05). Compared with the control group, the experimental group exhibited significantly lower VAS scores and higher satisfaction scores at 1, 4, and 8 weeks post-treatment (P<0.05), as well as significantly lower PSQI, GAD-7, and PHQ-9 scores at 4 and 8 weeks (P<0.05). There were no statistically significant differences between the two groups in the incidence of PHN, rescue analgesia, or adverse events (all P>0.05). This study demonstrates that compared with TPVB alone, the combination of TPVB and Pecs block provides better pain relief, improves sleep quality, and alleviates anxiety and depression in middle-aged and elderly patients with upper thoracic AHN, with a favorable safety profile.

Humans

The analgesic efficacy of intrathecal morphine compared to peripheral regional analgesia in total hip arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Following elective total hip arthroplasty, pain continues to be a significant problem. Intrathecal morphine or peripheral regional analgesia, that is local infiltration analgesia or peripheral nerve block, are common analgesic modalities, but it is still not known which is superior. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: The following electronic databases were searched from inception to 24 March 2026: CENTRAL; Ovid Embase; Ovid MEDLINE; Scopus; and Web of Science. ELIGIBILITY CRITERIA: Randomised controlled trials that compared intrathecal morphine to peripheral regional analgesia in patients scheduled for elective total hip arthroplasty under general or spinal anaesthesia. RESULTS: Eight trials and 471 patients were included. The peripheral regional analgesia was peripheral nerve block in six trials and local infiltration analgesia in two trials. No difference was demonstrated between intrathecal morphine and peripheral regional analgesia in regard to the first coprimary outcome, the pain score at rest at 24&#x200a;h. The quality of evidence was moderate. Intrathecal morphine was found to be superior to peripheral regional analgesia with respect to the second coprimary outcome, the cumulative intravenous morphine equivalent consumption at 24&#x200a;h. Mean difference (95% CI) was 11.38&#x200a;mg (4.31-18.45; P &#x200a;=&#x200a;0.002, I2 &#x200a;=&#x200a;81%). The quality of evidence was low. Intrathecal morphine was revealed to be superior to peripheral regional analgesia at 8-12&#x200a;h for the pain score at rest, 1.24 (0.60-1.88); P &#x200a;=&#x200a;0.0001, I2 &#x200a;=&#x200a;68%; pain score on movement, 1.15 (0.12-2.17), P &#x200a;=&#x200a;0.03, I2 &#x200a;=&#x200a;65%; but the rate of in hospital pruritus was reduced with peripheral regional analgesia, 0.31 (0.17-0.58), P &#x200a;=&#x200a;0.0002, I2 &#x200a;=&#x200a;0%. No differences in functional status were shown. CONCLUSIONS: We found no difference between intrathecal morphine and peripheral regional analgesia in regard to pain score at rest at 24 h. Intrathecal morphine may lead to a favourable effect on some but not all analgesic indices compared to peripheral regional analgesia in elective total hip arthroplasty. The quality of evidence for these positive effects was low. Intrathecal morphine reduced the systemic opioid consumption, but is not in itself an opioid free strategy. This notion is supported by the increased incidence of in hospital pruritus with intrathecal morphine. The quality of evidence for this was high. In view of the quality of evidence, high quality randomised controlled trials are required to substantiate these results.

Humans

Deucravacitinib 5-Year Safety and Efficacy Results in Plaque Psoriasis: A Phase 3 Open-Label Extension of Randomized Clinical Trials.

BACKGROUND: Deucravacitinib, an oral, selective, tyrosine kinase 2 inhibitor, is approved for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy and for adults with active psoriatic arthritis. OBJECTIVE: We evaluated deucravacitinib safety and efficacy over 5 years in the phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials in patients with moderate to severe plaque psoriasis. METHODS: PSO-1 and PSO-2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At 52 weeks, patients enrolled in the LTE trial received open-label deucravacitinib. Safety was reported as exposure-adjusted incidence rates (EAIRs) per 100 person-years (PY). Clinician- and patient-reported outcomes were analyzed using modified nonresponder imputation in patients receiving continuous deucravacitinib from day 1 (PSO-1/PSO-2) through 5 years. RESULTS: Overall, 1519 patients received one or more deucravacitinib dose; total exposure was 5046.7 PY through data cutoff (September 2, 2024). EAIRs/100 PY were comparable or decreased from the 1-year to 5-year cumulative period for adverse events (AEs) (229.23, 127.40, respectively), serious AEs (5.68, 5.06), discontinuation due to AEs (4.38, 2.09), deaths (0.20, 0.22), serious infections excluding coronavirus disease 2019 (COVID-19) (1.53, 0.94), malignancies (1.02, 0.92), major adverse cardiovascular events (0.30, 0.34), and venous thromboembolism (0.20, 0.06). Clinical outcomes were well-maintained in patients receiving continuous deucravacitinib (n = 513) from 1 through 5 years, including achievement of a &#x2265;&#xa0;75% reduction from baseline in the Psoriasis Area and Severity Index (1 year, 72.1% [95% CI 68.2-76.1]; 5 years, 67.3% [62.0-72.6]) and a static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (1 year, 57.5% [53.1-61.9]; 5 years, 52.6% [47.0-58.1]). Dermatology Life Quality Index 0 or 1 was well-maintained from 1 year (52.5% [48.0-57.1]) through 5 years (45.4% [40.0-50.8]). CONCLUSIONS: These findings demonstrate a consistent safety profile with no new safety signals and durable clinical response through 5 years of treatment with deucravacitinib. CLINICAL TRIAL REGISTRATION: NCT03624127, NCT03611751, NCT04036435.

Humans

Clinical outcomes of Epstein-Barr virus infection/reactivation following CAR-T cell therapy: A systematic review.

BACKGROUND: Epstein-Barr virus (EBV) infection or reactivation is an emerging but underrecognized complication following chimeric antigen receptor T-cell (CAR-T) therapy and is likely associated with treatment-induced immune dysregulation. Data regarding its clinical impact remain limited. OBJECTIVE: To evaluate the reported occurrence, clinical manifestations, and outcomes of EBV infection or reactivation in adults undergoing CAR-T therapy. METHODS: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Embase, and Cochrane CENTRAL were searched from inception to March 2025 for studies reporting EBV infection or reactivation after CAR-T therapy in adults. Due to limited and heterogeneous data, results were synthesized descriptively. RESULTS: Five studies comprising 80 patients were included (median age, 55&#xa0;years; 52.6% male among patients with reported sex data [10/19]). Across the included studies, 11 EBV infection/reactivation events were identified among 80 described CAR-T recipients, representing 13.8% of the reported sample rather than a true incidence estimate. Among events with usable individualized timing data, the median interval from CAR-T infusion to EBV detection/reactivation was 9.8&#xa0;months (approximate range, 1-44&#xa0;months). Because EBV surveillance strategies and definitions were inconsistently reported across studies, this proportion should not be interpreted as a true incidence estimate. Four patients (36.4%) developed EBV-associated disease, including three cases of EBV-related lymphoproliferative disorder and one case of EBV-associated diffuse large B-cell lymphoma. Among seven patients with reported post-CAR-T treatment response, four achieved Complete Remission/ Continuous Complete Remission; treatment response should be interpreted separately from final survival status. Confirmed EBV-related mortality occurred in 2/11 patients with reported EBV infection/reactivation and in 2/4 patients with EBV-associated disease; all-cause mortality could not be reliably estimated because patient-level vital status could not be fully attributed to the EBV-reactivated subgroup. Reported toxicities predominantly consisted of low-grade cytokine-release syndrome; however, toxicity data were limited. CONCLUSION: Although infrequently reported, EBV infection or reactivation after CAR-T therapy may be associated with substantial morbidity and mortality among affected patients. However, the available evidence is limited by the small sample size, heterogeneous study designs, and inconsistent EBV surveillance practices.

Humans

Outcome of conservative management of small renal stones in prepubertal children.

INTRODUCTION: Renal stones are relatively uncommon in the pediatric population. This study aimed to evaluate the utility of conservative management of small renal stones in prepubertal children. PATIENTS AND METHODS: A retrospective chart review was conducted for children (&#x2264;12 years old) with small renal stones (3-10 mm) from 2016 to 2023 who underwent conservative management. Management included periodic renal ultrasonography, every 6 months, in addition to good hydration. Stones were confirmed by two consecutive ultrasounds. We recorded the patient's demographics and ultrasound findings (stone side, size, laterality, location, number, and associated hydronephrosis). Surgical intervention was indicated if recurrent loin pain, recurrent UTI, or worsening hydronephrosis (obstructing stone). Nephrolithiasis was considered resolved if stones were not visualized on 2 consecutive ultrasounds. Moreover, we evaluated conservative management outcomes for those presented during infancy (<12 months) versus later. RESULTS: We included 52 patients (65renal units) who presented at a median age of 46.1months (5.3-155.1). Seventy-five percent of patients had incidental renal stones. The median stone size was 4 mm (3-10). Forty-six percent of stones were in the lower calyx. The majority (70.8 %) had no hydronephrosis at presentation. During a median follow-up of 39months, 15patients with 17units (26.2 %) were documented stone-free. Ten patients (19.2 %) had symptomatic stone events, all measured &#x2265;4 mm. Of them, 6 patients (6 units) underwent surgical interventions, and 4 patients (4 units) experienced complications. A ROC curve analysis identified a stone size cutoff of 4 mm (sensitivity 100 % and 29 % specificity) that could be associated with symptomatic stone events. Using a multivariate Cox regression model, stone size was the only significantly associated factor with subsequent surgical intervention (p = 0.007). 19 % (10patients,12units) presented during infancy. Notably, the incidence of stone-free rate was significantly higher during infancy compared to older children (58.3 % vs 18.9 %,respectively). DISCUSSION: During a 39-month follow-up, 4 patients developed complications (2recurrent pain and 2 experienced UTI), supporting the safety of conservative management of small renal stones. This study is limited due to its retrospective design and the reliance on ultrasound as the main imaging method. To minimize that, all ultrasound images were carefully reviewed by two pediatric urologists. Moreover, renal stones were confirmed using strict criteria, which required detection in two consecutive ultrasounds. CONCLUSION: Although 26.2 % of units had spontaneously resolved nephrolithiasis, surgical intervention was only required in 11.5%of patients, all of whom had renal stones&#x2265;4 mm. Infants had higher spontaneous resolutions without complications, suggesting that conservative management may be especially effective in this subgroup.

Humans

The Childhood Cancer and Leukemia International Consortium (CLIC): Expanding global collaboration in pediatric cancer etiology research.

Childhood cancers are rare, but incidence has risen modestly in countries with robust registration, partly reflecting improved diagnosis. In high-income countries, cancer is the leading cause of disease-related death in children. Marked inequities in incidence, survival, and research capacity underscore the need for large-scale collaboration to identify environmental, genetic, and contextual determinants of risk. The Childhood Cancer and Leukemia International Consortium (CLIC) was established in 2007 to study the etiology of childhood leukemia and later expanded in 2019 to include other childhood cancers, principally solid tumors. CLIC pools harmonized, individual-level data from case-control and cohort studies, obtained through interviews, record linkage (insurance claims, registries), or geographic information systems, and integrates germline genomic data where available. Membership has grown from 13 studies in 9 countries to 57 studies in 21 countries; recruitment spans the early 1960s to the present and encompasses approximately 150,000 cases across all tumor types and 300,000 controls with clinical, demographic, and exposure data, centralized via harmonized data dictionaries at the Data Coordination Center, established in 2014 at the International Agency for Research on Cancer, and supported by a secure analysis platform. Pooled analyses across diverse populations have implicated parental age, prenatal vitamin or folic acid use, mode of delivery, fetal growth, selected congenital anomalies, occupational or household exposures (e.g., pesticides), paternal smoking, and markers of early-life immune modulation (e.g., breastfeeding, daycare attendance) in leukemia risk, informing carcinogen evaluation and prevention. The integration of genetic ancestry and germline susceptibility data is clarifying ancestry-related differences in leukemia biology and outcomes, while confirming risk loci with population-specific effects. CLIC is now adding polygenic risk scores and exposomic data to refine etiologic subtyping and identify modifiable pathways, while broadening representation from underserved regions through partnership-building and capacity-strengthening.

Humans