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Online-delivered eye movement desensitization and reprocessing treatment for adults with post-traumatic stress disorder due to multiple traumas: a non-concurrent multiple baseline design.

Background: No controlled studies incorporating randomization have been conducted to investigate the effectiveness of online eye movement desensitization and reprocessing (EMDR) treatment, despite its use in clinical practice.Objective: This study evaluated the effect of online EMDR treatment in adults aged 18-65 years with post-traumatic stress disorder (PTSD) resulting from multiple traumas.Method: A multiple baseline single-case experimental design (n = 21) was employed. Participants were patients with PTSD due to multiple traumas, recruited from a mental healthcare institution in the Netherlands. They were randomly assigned to baseline phases of 2, 3.5, or 5.5 weeks. After this, participants received 10 weekly online EMDR sessions. The primary outcome was the total score on an adapted version of the PTSD Checklist for DSM-5 (PCL-5), which was administered twice a week during baseline and intervention phases, and once 12 weeks after the end of the intervention phase. We performed visual analysis and calculated the improvement rate difference (IRD) for each individual separately to determine whether online EMDR was effective. We also performed a paired t-test and calculated Cohen's d for pretreatment and post-treatment comparisons, and pretreatment versus follow-up to evaluate effects at the group level.Results: Visual analysis and IRD scores showed that the treatment was effective for 15 participants, with effect sizes ranging from small to very large. The mean scores on the PCL-5 at group level decreased significantly over time between pretreatment and post-treatment (Mdiff = 23.6, Cohen's d = 1.34, 95% CI 0.74-1.93), as well as between pretreatment and follow-up (Mdiff = 27.2, Cohen's d = 1.62, 95% CI 0.95-2.27).Conclusion: Most participants showed a reduction in symptoms following the start of the online EMDR. Furthermore, at the group level there was a significant and clinically relevant reduction in symptoms over time. This provides preliminary evidence for the effectiveness of online EMDR treatment.

Humans

Multi-omics reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function.

Renal fibrosis (RF), a common pathological process driving chronic kidney disease (CKD) progression to end-stage renal failure, is closely associated with oxidative phosphorylation (OXPHOS). Arctigenin (ATG), the main active component of burdock seed, exhibits anti-inflammatory and anti-fibrotic activities, but its mechanisms in RF treatment remain unclear. Here, we performed integrated transcriptomic and proteomic analyses to identify key targets and pathways of ATG in a unilateral ureteral obstruction-induced rat RF model. Multi-omics enrichment analysis revealed that NDUFS8 and NDUFS2 were the core targets of ATG, with the OXPHOS pathway as the central intersecting pathway. Our results suggest that ATG exerts anti-renal fibrosis effects by targeting the OXPHOS pathway to inhibit excessive reactive oxygen species production and oxidative stress. SIGNIFICANCE: Chronic kidney disease (CKD) continues to impose an escalating global health and socioeconomic burden, while renal fibrosis (RF), as the convergent pathological endpoint of virtually all progressive nephropathies, remains the principal determinant of irreversible renal failure and adverse clinical outcomes. Despite extensive efforts to develop antifibrotic therapies, effective clinical interventions remain elusive, largely due to the complex and multifactorial nature of RF pathogenesis. In this study, we employed an integrated multi-omics framework encompassing transcriptomics, proteomics, and metabolomics to systematically decipher the antifibrotic mechanism of arctigenin (ATG), a bioactive natural compound derived from traditional Chinese medicine. Our findings identify mitochondrial oxidative phosphorylation as the pivotal regulatory axis underlying the renoprotective effects of ATG and further establish key catalytic subunits of mitochondrial complex I as its direct molecular targets. Mechanistically, ATG not only restores complex I activity and reprograms mitochondrial energy metabolism but also preserves the intracellular stability and localization of these subunits, thereby preventing their aberrant release-mediated inflammatory activation and disrupting the self-perpetuating cycle linking metabolic dysfunction, inflammation, and fibrosis progression. Beyond revealing a previously unrecognized dual mechanism integrating metabolic and inflammatory regulation, this study provides compelling evidence that mitochondrial dysfunction is not merely a secondary consequence of tissue injury but a fundamental driver of fibrotic remodeling. Importantly, our work highlights the translational potential of natural product-based mitochondrial interventions for CKD treatment and supports a broader conceptual shift toward metabolism-centered therapeutic strategies for chronic fibrotic diseases. Given the central role of mitochondrial dysfunction across multiple organs, these findings may also have far-reaching implications for the treatment of systemic fibrosis-related disorders beyond the kidney.

Animals

Sodium-glucose cotransporter-2 inhibitors and gastrointestinal neoplasm risk in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

The potential carcinogenic effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) remain controversial, particularly regarding site-specific gastrointestinal (GI) neoplasms. This systematic review and meta-analysis aimed to determine the relationship between SGLT2 inhibitors and the risk of GI neoplasms in patients with T2DM. We searched PubMed, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science through March 17, 2025, for RCTs in T2DM comparing SGLT2 inhibitors with placebo or active comparators. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. The primary outcome was GI neoplasms reported in publications, supplementary materials, or trial registries, usually as adverse events rather than centrally adjudicated cancer endpoints. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in Stata 17.0. In 48 RCTs (n = 48,765), SGLT2 inhibitor therapy was not associated with overall GI neoplasm risk (OR = 1.10, 95% CI: 0.84-1.44; p = 0.46; I² = 0%). Site-specific analyses showed no statistically significant association for esophageal (OR = 1.12, 95% CI 0.37-3.45), gastric (1.20, 0.65-2.23), hepatic (0.62, 0.31-1.22), pancreatic (0.91, 0.51-1.64), colonic (1.28, 0.78-2.08), colorectal (0.76, 0.27-2.17), and rectal neoplasms (0.98, 0.49-1.97), with all p-values > 0.05. Subgroup analyses by agents (e.g., canagliflozin, dapagliflozin, empagliflozin), baseline age, body mass index (BMI), HbA1c, treatment duration, and dose were also non-significant (all p > 0.05). Approximately half of the trials had follow-up of one year or less, limiting our ability to evaluate long-term risk. Available RCT evidence does not show a clear increase in GI neoplasm risk with SGLT2 inhibitors in T2DM. However, limited follow-up, low event counts, and non-cancer-specific outcome ascertainment, the findings should be interpreted as reassuring but not definitive evidence of long-term oncologic safety.Systematic review registration: PROSPERO No. CRD42024619019.

Humans

Paramedian supracerebellar transtentorial approach for Yaşargil T2 tentorial incisura meningiomas.

OBJECTIVE: Tentorial incisura meningiomas, particularly those arising from the middle incisural region (Yaşargil T2), are surgically challenging because of their deep location and compression of critical neurovascular structures. These lesions typically have supratentorial or infratentorial extension but can also extend across both compartments. Although approach selection is often guided by the dominant compartment of tumor extension, for lesions with supratentorial-dominant extension, the optimal approach remains controversial, and a standardized strategy has not been established. Authors of this study evaluated the feasibility and outcomes of the paramedian supracerebellar transtentorial (PST) approach for Yaşargil T2 tentorial incisura meningiomas with a supratentorial-dominant or combined extension. METHODS: The authors retrospectively reviewed data from consecutive patients with radiographic and intraoperative findings consistent with a Yaşargil T2 tentorial incisura lesion treated via the PST approach from September 2005 through December 2025. Patients were placed in a semisitting position whenever feasible and in a semilateral position when semisitting was contraindicated. Collected data included demographics, tumor extension patterns, extent of resection on postoperative MRI, neurological outcomes, histopathology, rate of recurrence, and follow-up. RESULTS: Six patients, 1 male and 5 female, with an overall mean age of 43 years, underwent resection via the PST approach. Four lesions had predominantly supratentorial extension, and 2 had combined supra- and infratentorial growth, with no cases of isolated infratentorial extension. Five patients had been placed in the semisitting position and 1 in a semilateral position because of a cardiac contraindication to the semisitting position. No new permanent neurological deficits were observed. Postoperative MRI showed Simpson grade I resection in all 6 patients. The mean follow-up was 8.6 years. Histopathological analysis revealed 3 WHO grade 1 meningiomas, 1 WHO grade 2 meningioma (clear cell), and 2 solitary fibrous tumors (meningioma mimics). These diagnoses were evaluated according to the 2021 WHO classification. CONCLUSIONS: In this consecutive series, the PST approach was a viable single-corridor strategy for Yaşargil T2 tentorial incisura lesions, including supratentorial-dominant tumors, achieving Simpson grade I resection with no permanent neurological deficits. By providing early devascularization at the tentorial attachment and a gravity-assisted, retractorless working corridor with favorable deep venous visualization, the PST approach challenges compartment dominance as the primary determinant of approach selection.

Humans

Hand Pain and Sensory Deficits: Carpal Tunnel Syndrome: 2026 Revision. Using the Evidence to Guide Musculoskeletal Rehabilitation Practice.

SYNOPSIS: Carpal tunnel syndrome is common in women, manual laborers, and during pregnancy; it is often associated with medical conditions such as obesity and diabetes. The musculoskeletal rehabilitation clinician's approach to managing hand pain and sensory deficits associated with carpal tunnel syndrome should include prescribing a neutral-positioned wrist orthosis plus instructing the patient on how to modify activities, adjust ergonomics, and reduce exposure to risk factors. Here, we present for clinicians the most up-to-date information to guide their work in managing hand pain and sensory deficits associated with carpal tunnel syndrome. J Orthop Sports Phys Ther 2026;56(9):622-623. doi:10.2519/jospt.2026.0502.

Humans

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

Specialized pro-resolving mediator (SPM)-enriched supplementation modulates inflammatory biomarkers in patients with symptomatic knee osteoarthritis: Blood plasma analysis from the GAUDI study.

BACKGROUND: Osteoarthritis (OA) is a leading cause of chronic pain and functional impairment, associated with persistent inflammation, potentially due to impaired resolution. Specialized pro-resolving lipid mediators (SPMs) regulate inflammation resolution and restore homeostasis. The GAUDI study previously demonstrated that SPM supplementation reduces pain and improves quality of life (QoL) in patients with knee OA. This analysis assesses the impact of SPM supplementation on inflammatory biomarkers (IB) and SPM levels and their relationship with clinical outcomes. METHODS: This is a secondary analysis of the GAUDI trial, a randomized, multicenter, double-blind, placebo-controlled study conducted in Spain in adults with symptomatic knee OA who received daily supplementation with SPMs or placebo for 12 weeks. Endpoints included changes in plasma IB and SPM levels and their correlation with clinical outcomes. RESULTS: Changes in IL-1 (15.9 vs. -1.1 pg/ml, p-value: 0.051) and IL-18 (10.3 vs. -1.4 pg/ml, p-value: 0.29) showed a tendency toward reduction in the SPM group compared to the placebo group. Changes in IL-1 and IL-8 positively correlated (r = 0.707, p-value: 0.005 and r = 0.551, p-value: 0.04; respectively) with changes in WOMAC score and negatively correlated (r = -0.797, p-value <0.001 and r = -0.804, p-value <0.001; respectively) with changes in EuroQoL-5 VAS score. Changes in IL-1 (r = 0.554, p-value: 0.048) and IL-6 (r = 0.631, p-value: 0.014 and r = 0.572, p-value: 0.031) correlated with changes in OMERACT-OARSI pain score. No significant differences in IB levels were observed between groups during the intervention. Minor changes in SPM levels point to metabolic pathways at work with SPM supplementation. In patients with a BMI &#x2265;25 kg/m&#xb2;, most IB tended to decrease following SPM consumption. CONCLUSIONS: This analysis suggests a potential association between SPM supplementation, decreased inflammation, and improved pain and QoL in patients with knee OA. Subtle changes in blood plasma SPM levels were detected that indicate, through bioinformatics analysis, a pathway-specific metabolome activation induced by SPM supplementation. TRIAL REGISTRATION: NCT05633849. Registered December 1st, 2022. Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT05633849.

Humans

'Sawa Aqwa' (Stronger Together): A multi-site randomized controlled trial of a brief family systemic intervention for adolescent mental health in Lebanon.

BACKGROUND: There are no evaluated family-based mental health and psychosocial support (MHPSS) interventions for adolescents in Southwest Asia (known as the Middle East), and few whole-family interventions in low- and middle-income countries, despite consistent evidence for the impact of family support on mental health and well-being. This study aims to evaluate the effectiveness of a brief family systemic mental health intervention, deliverable by non-specialists in mental health. METHODS: We conducted an assessor-blind type I hybrid effectiveness-implementation multi-site randomized controlled trial comparing the locally developed family intervention to a waitlist control group for randomly allocated families residing in North Lebanon and Beqa'a governorates. Eligible families presented with medium-to-high risk for child protection concerns (abuse, neglect, child labor, early marriage) and had at least one adolescent aged 12-17 who demonstrated psychological distress. Outcomes at the family, caregiver, and adolescent level were measured pre- and post-intervention, and at 3-month follow-up. RESULTS: Intent-to-treat analyses found a significant between-group effect of the intervention on adolescent-reported family functioning, caregiver mental health, and parenting. No change was found for adolescent psychological distress. Further analyses found effects on adolescent well-being for those who completed the intervention, and that father attendance was associated with better outcomes for adolescent well-being in the intervention group. No other significant moderators were found. At the 3-month follow-up for the intervention condition, family functioning and caregiver well-being significantly dropped from endline. CONCLUSIONS: The study demonstrates mixed results for a non-specialist-delivered family-systemic intervention developed in the context of humanitarian crises in Lebanon. While the intervention did not result in benefits in adolescent-reported symptoms of psychological distress, the intervention group did show greater improvements than the control group on a number of other outcomes, showing the potential impact of working with the wider family system to support adolescents in humanitarian settings.

Humans

Intravenous lidocaine reduces the propofol EC50 for loss of consciousness and intraoperative anesthetic consumption in gynecological laparoscopy: A randomized controlled trial.

BACKGROUND: Intravenous lidocaine reduces propofol requirements and procedure-related adverse events. OBJECTIVES: The study aimed to test whether intravenous lidocaine would reduce the effect-site concentration of propofol required to achieve loss of consciousness and decrease propofol consumption during total intravenous anesthesia in gynecological laparoscopy. METHODS: This was a prospective, randomized, double-blind, placebo-controlled trial. Sixty patients were randomly allocated to receive either intravenous lidocaine (1.5 mg&#xb7;kg-&#xb9; bolus) followed by continuous infusion or an equal volume of saline. Propofol was administered via target-controlled infusion starting at an effect-site concentration of 3.5 &#x3bc;g/mL. The concentration was then adjusted in steps of 0.5 &#x3bc;g/mLaccording to Dixon's up-and-down sequential method: decreased if loss of consciousness was achieved, or increased if not. Loss of consciousness was defined as loss of response to verbal commands. The median effective concentration (EC50) of propofol for inducing loss of consciousness was calculated using the Dixon's up-and-down method. General anesthesia was maintained with propofol and remifentanil, guided by state entropy (target 40-60) and surgical pleth index (target 20-50). Drug consumption was normalized to anesthesia duration and body weight. RESULTS: The estimated EC50 of propofol for inducing loss of consciousness was significantly lower in the lidocaine group than in the saline group (3.32 &#x3bc;g/mL, 95% Confidence Interval (CI): 3.04-3.59 vs. 3.89 &#x3bc;g/mL, 95% CI: 3.50-4.28). Under the study protocol, the lidocaine group also required less propofol (8.62 mg&#xb7;kg-1&#xb7;h-1, 95% CI: 8.10-9.15 vs. 9.89 mg&#xb7;kg-1&#xb7;h-1, 95% CI: 9.05-10.73) and less remifentanil (0.23 &#x3bc;g&#xb7;kg-1&#xb7;min-1, 95% CI: 0.21-0.24 vs. 0.27 &#x3bc;g&#xb7;kg-1&#xb7;min-1, 95% CI: 0.24-0.30) compared with the saline group. CONCLUSION: Intravenous lidocaine reduced the propofol EC50 for Loss of Consciousness (LOC) and decreased intraoperative propofol and remifentanil consumptions in patients undergoing gynecological laparoscopy. These findings suggest a propofol- and opioid-sparing effect of intravenous lidocaine in this setting, although confirmation in larger multicenter trials is needed.

Humans

Corneal Epithelial Alterations Associated With Cyclin-Dependent Kinase 4/6 Inhibitor Therapy in Hormone Receptor-Positive Breast Cancer.

IMPORTANCE: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard therapy for hormone receptor-positive (HR+), HER2-negative breast cancer. By blocking the G1/S cell-cycle transition, these agents may impair renewal of the corneal epithelium. No controlled study has systematically evaluated corneal epithelial changes in patients receiving CDK4/6 inhibitors. OBJECTIVE: To determine whether CDK4/6 inhibitor-based therapy is associated with cornealepithelial alterations independent of aromatase inhibitor exposure and tear film dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Retrospective comparative cross-sectional study at a tertiary ophthalmology center. A total of 132 women were enrolled: 45 receiving a CDK4/6 inhibitor plus an aromatase inhibitor (CDKAI group), 44 receiving aromatase inhibitor monotherapy (AI group), and 43 age-matched postmenopausal controls without systemic oncologic therapy. EXPOSURES: CDK4/6 inhibitor (ribociclib, palbociclib, or abemaciclib) combined with an aromatase inhibitor; aromatase inhibitor alone; or no systemic oncologic therapy. MAIN OUTCOMES AND MEASURES: Prevalence and severity of punctate epitheliopathy and vortex keratopathy, assessed by a masked ophthalmologist. Secondary outcomes included Schirmer I test, tear film break-up time, and Ocular Surface Disease Index (OSDI). RESULTS: PE was present in 44.4% of eyes in the CDKAI group vs 4.7% in the AI group and 2.3% in controls (&#x3c7;&#xb2; = 34.31; P < .001). All moderate (13.3%) and severe/complicated (8.9%) PE cases occurred exclusively in the CDKAI group. Vortex keratopathy was observed in 13.3% of CDKAI patients and in none of the other groups (P = .025). Schirmer values, tear film break-up time, and OSDI scores did not differ among groups (all P > .05). Within the CDKAI group, PE was not associated with treatment duration (P = .963) or tear film parameters. CONCLUSIONS AND RELEVANCE: In this comparative study, CDK4/6 inhibitor-based therapy was associated with significantly higher prevalence and severity of PE and vortex keratopathy, independent of aromatase inhibitor exposure and in the absence of measurable tear film dysfunction. These findings suggest a direct cytostatic effect on the corneal epithelium. Symptom scores were low, although OSDI interpretation was limited by incomplete responses. Proactive corneal surface evaluation with fluorescein staining may be warranted during CDK4/6 inhibitor treatment.

Humans

Efficacy and safety of Janus kinase inhibitors in Beh&#xe7;et's disease: A systematic literature review.

INTRODUCTION: Beh&#xe7;et's disease e (BD) is a chronic, relapsing, multisystem inflammatory disorder that if not successfully treated can lead to severe, organ or life-threatening complications. Despite treatment with glucocorticoids, immunosuppressants, and tumor necrosis factor (TNF) inhibitors, some patients still have refractory disease that mandates additional therapeutic options. The pathogenesis of BD involves dysregulated innate and adaptive immune responses with multiple cytokines signaling through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. By targeting multiple inflammatory pathways, JAK inhibitors have emerged as a promising therapeutic option. However, current evidence remains limited and heterogeneous. Therefore, we conducted this systematic review to evaluate their efficacy and safety in BD. METHODS: We conducted a systematic literature review in accordance with PRISMA 2020 guidelines (PROSPERO registration: CRD420261381955). PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched from inception to March 2026. Original clinical studies evaluating Janus kinase (JAK) inhibitors in BD were included. Two reviewers independently performed study selection, data extraction, and quality assessment using Joanna Briggs Institute tools. Due to heterogeneity, results were synthesized narratively, focusing on efficacy and safety outcomes. RESULTS: Seventeen studies (99 patients) were included, predominantly case reports and small observational cohorts with overall high methodological quality. All evaluated tofacitinib, baricitinib, or upadacitinib, with no data on other JAK inhibitors. Patients were highly treatment-refractory, with prior failure of conventional and biologic therapies. Upadacitinib was the most frequently studied agent and demonstrated an overall response rate of 85.2% and complete remission in 59.3% in a multi-center study. Efficacy was observed across multiple domains, with the most consistent responses in intestinal disease, including clinical and endoscopic remission, alongside frequent glucocorticoid-sparing effects. Safety findings were consistent with known JAK inhibitor safety profiles, with mainly mild to moderate infections and manageable laboratory abnormalities, and no clear signal for increased thrombotic events, although follow-up was limited. CONCLUSION: JAK inhibitors demonstrate promising efficacy in BD, particularly in refractory and multisystem disease. The most consistent evidence of efficacy was observed in gastrointestinal involvement, whereas data for other disease domains remain limited. Their safety profile appears consistent with existing data, although further follow up and validation is required. High-quality randomized controlled studies are an imminent need to study the potential role of JAK inhibitors in BD.

Humans

[Clinical efficacy and cost-effectiveness evaluation of acupoint thread-embedding for knee osteoarthritis of early to middle stage].

OBJECTIVE: To compare the clinical efficacy of acupoint thread-embedding and electroacupuncture for knee osteoarthritis (KOA) of early to middle stage, and to evaluate their economic benefits based on cost-effectiveness analysis. METHODS: A total of 66 patients with KOA of early to middle stage were randomized into an acupoint thread-embedding group (33 cases, 1 case dropped out) and an electroacupuncture group (33 cases, 2 cases dropped out). In the acupoint thread-embedding group, acupoint thread-embedding was applied at Xuehai (SP10), Liangqiu (ST34), Weizhong (BL40), etc.on the affected side, once a week. In the electroacupuncture group, electroacupuncture was applied at Xuehai (SP10),Liangqiu (ST34), Zusanli (SP36), etc. on the affected side, with disperse-dense wave, in frequency of 2 Hz/100 Hz, once every other day, 3 times a week. Both groups were treated for 4 weeks. The Western Ontario and McMaster Universities arthritis index(WOMAC) score was observed before and after treatment, as well as at the follow-up of 4 weeks after treatment completion,the visual analogue scale (VAS) score of pain and the Lysholm score were observed before and after treatment in the two groups. The clinical efficacy was evaluated between the two groups, and the cost-effectiveness analysis was conducted based on WOMAC score. RESULTS: After treatment, the WOMAC and pain VAS scores were decreased compared with those before treatment (P<0.001), and the Lysholm scores were increased compared with those before treatment (P<0.001) in both groups. At follow-up, the WOMAC score in the acupoint thread-embedding group was decreased compared with that before treatment (P<0.001), and was lower than that in the electroacupuncture group (P<0.05). The total effective rates were 93.8% (30/32) in the acupoint thread-embedding group and 87.1% (27/31) in the electroacupuncture group, with no statistically significant difference between the two groups (P>0.05). The cost-effectiveness ratio (CER) and the total cost of the acupoint thread-embedding group were lower than those in the electroacupuncture group. CONCLUSION: Both acupoint thread-embedding and electroacupuncture can improve knee joint function, pain and stability in patients with KOA of early to middle stage, with comparable efficacy, and the acupoint thread-embedding group shows better long-term efficacy, lower cost and higher economic benefit.

Humans

How I do it: 3-Suture robotic pyeloplasty: Step-by-step technique.

Robot-assisted pyeloplasty is now a gold standard in the treatment of pediatric ureteropelvic junction obstruction. We describe a standardized "3-suture" technique designed to facilitate the pyelo-ureteral anastomosis. We used this technique in 65 paediatric patients aged 3-17 years. Early major complications (Clavien-Dindo grade III) occurred in 3 patients (4.6%). The median operative time was 150 min. Surgical success was achieved in 96% of cases at a median follow-up of 9.5 months. This 3-suture approach offers a highly reproducible method for robotic pyeloplasty, facilitating accurate anatomical reconstruction with excellent surgical outcomes.

Humans

Temporal proteomic analysis reveals a three-phase adaptation strategy in Phytophthora cinnamomi during salinity stress.

Phytophthora cinnamomi, a highly invasive hemibiotrophic oomycete, threatens global agriculture, forestry, and native ecosystems. Although drought and temperature effects on P. cinnamomi-host interactions are well studied, current knowledge of abiotic stress responses in P. cinnamomi remains largely centered on infection and phytopathology, with limited molecular insight into the pathogen's direct response to salinity independent of its host. To address this gap, we combined growth assays, time-resolved proteomics, and network analysis to define how P. cinnamomi responds and adapts to salinity exposure. Growth assays showed that NaCl-modified agar enhanced mycelial expansion in a concentration-dependent manner, with 100&#xa0;mM NaCl significantly increasing growth at 48, 72, and 96&#xa0;h compared with controls, while 50&#xa0;mM NaCl remained comparable to control conditions. Temporal proteomic analysis of 100&#xa0;mM NaCl treatment at 0, 1, 6, 12, and 24&#xa0;h post treatment revealed dynamic shifts in protein abundance. Early induction of ROS (Reactive Oxygen Species)-detoxifying enzymes, including glutathione S-transferases and peroxidases, was consistent with ROS-specific staining assays. Network analysis identified modules enriched for redox regulation, ATP generation, ion transport, and translational control, highlighting multi-layered adaptation to elevated NaCl levels. Notably, clusters of conserved hypothetical proteins were strongly upregulated, indicating unexplored stress tolerance components in Phytophthora species. Here, we propose that P. cinnamomi rapidly activates a three-phase strategy involving metabolism readjustments, redox defenses, and cellular structure alterations under salinity conditions. With increasing soil salinization due to climate change, our study provides first mechanistic insights into P. cinnamomi's adaptive plasticity and ecological resilience to abiotic stress. SIGNIFICANCE: This study represents the first temporal proteomic analysis of salinity stress adaptation in Phytophthora cinnamomi, revealing a sophisticated three-phase adaptation strategy. This research fundamentally advances our understanding of how this globally destructive plant pathogen, P. cinnamomi, maintains environmental resilience. Our findings reveal proteome remodelling as a mechanistic framework for understanding stress tolerance in oomycetes, a group of microorganisms responsible for some of the world's most destructive agricultural and forest diseases. Our results show proteins involved in emergency damage control through metabolic recalibration to sustained adaptation. These findings have relevance for predicting pathogen behavior under climate change scenarios, where increasing soil salinity threatens agricultural productivity while simultaneously enhancing pathogen survival and virulence. Understanding how P. cinnamomi responds to prolonged salinity exposure may inform targeted biocontrol strategies and improve predictive models of disease pressure in salt-affected agricultural regions. The temporal analysis framework we present offers a broadly applicable approach for understanding microbial stress adaptation, with implications extending beyond plant pathology to environmental microbiology and biotechnology applications where stress tolerance is paramount.

Phytophthora

Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial.

AIMS: The endothelium maintains vascular health by regulating blood flow and protecting against inflammatory damage. In type 2 diabetes (T2DM), however, hyperglycemia, hypertension, and hyperlipidemia place a significant burden on the endothelium, potentially leading to atherosclerosis and cardiovascular disease (CVD). While semaglutide and empagliflozin have been shown to reduce CVD risk in T2DM, it remains unclear whether these benefits are mediated by improved endothelial function. This post-hoc analysis explores the effects of these agents on markers of endothelial function, i.e. the reactive hyperaemic index (RHI) and the endothelial-derived cell adhesion molecules (CAMs) E-Selectin, ICAM-1, P-Selectin, and VCAM-1. METHODS: This was a post-hoc analysis of a 32-week randomized trial evaluating the separate and combined effects of semaglutide and empagliflozin on cardio-renal organ damage. One hundred and twenty participants with type 2 diabetes, age&#xa0;&#x2265;&#xa0;50 were randomized to four groups (semaglutide, empagliflozin, the combination or placebo). An increase in RHI and/or a decrease in CAMs were considered beneficial. RESULTS: RHI increased compared to baseline (0.11, 95%CI [0.008;0.21], p&#xa0;=&#xa0;0.03) but not compared to placebo in the semaglutide group (0.11, 95%CI [-0.04;0.24], p&#xa0;=&#xa0;0.16). There was no effect on RHI in the empagliflozin group. Compared to placebo, E-Selectin decreased significantly in the semaglutide and combination groups (-9, 95%CI [-14.1;-5.1] p&#xa0;<&#xa0;0.01 and&#xa0;-&#xa0;9, 95%CI [-14.3; -5.2] p&#xa0;<&#xa0;0.01, respectively). VCAM-1 increased in the same groups, compared to placebo (12.3, 95%CI[2.8;20.8] p&#xa0;=&#xa0;0.01 and 16.2, 95%CI [7.2;24.3], p&#xa0;<&#xa0;0.01, respectively).P-Selectin and ICAM-1 was not significantly affected in any of the groups, compared to placebo (p&#xa0;&#x2265;&#xa0;0.11 and p&#xa0;&#x2265;&#xa0;0.09, respectively). CONCLUSION: Semaglutide improved endothelial function compared to baseline, but not significantly versus placebo, which likely is due to limited power. CAM responses were heterogeneous, suggesting distinct roles in endothelial dysfunction and atherosclerosis. ClinicalTrialsRegister.eu: EudraCT 2019-000781-38.

Aged

Primary ACL Repair and Reconstruction in Isolated ACL Ruptures: Forgotten Joint Scores and the Association Between Residual Laxity and Joint Awareness.

BACKGROUND: Primary anterior cruciate ligament (ACL) repair has recently reemerged as a treatment option for carefully selected proximal ACL tears. However, evidence regarding patient-reported joint awareness and the relationship between postoperative laxity and joint awareness remains limited. PURPOSE: To compare joint awareness, clinical outcomes, and postoperative laxity between primary ACL repair and hamstring tendon autograft reconstruction in carefully selected patients with isolated ACL rupture, and to explore the association between residual laxity and postoperative joint awareness. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective cohort study included 85 patients with isolated ACL rupture treated with either primary ACL repair (n = 26) or hamstring autograft reconstruction (n = 59), with a minimum follow-up of 24 months. Clinical outcomes, including visual analog scale score, Lysholm score, International Knee Documentation Committee (IKDC) score, Tegner activity scale score, postoperative knee laxity, return to sport, and rerupture rates, were evaluated. The authors also used the Forgotten Joint Score-12 (FJS-12), a measure of joint awareness, to evaluate patients. A higher score reflects lower joint awareness, suggesting function more similar to a native knee. Multivariable regression analyses were performed to evaluate variables associated with postoperative FJS-12 values. RESULTS: No differences were observed between groups in postoperative Lysholm, IKDC, and Tegner activity scale scores; Lachman- and pivot-shift-assessed postoperative laxity; and return-to-sport rates. However, postoperative FJS-12 values were significantly higher in the repair group compared with the reconstruction group (87.0 &#xb1; 15.0 vs 77.5 &#xb1; 14.2; mean difference, 9.5 points [95% CI, 2.8-16.3]; P = .006), corresponding to a moderate effect size (Cohen d = 0.66). Secondary exploratory regression analyses demonstrated that residual postoperative laxity was associated with lower postoperative FJS-12 values in both Lachman- and pivot-shift-based models (R2 = 0.649 and 0.680, respectively; P < .001 for both). CONCLUSION: In carefully selected patients with proximal ACL tears and adequate tissue quality, no significant between-group differences were detected in conventional clinical outcomes, postoperative laxity, return-to-sport rates, or rerupture rates between primary ACL repair and reconstruction. Primary ACL repair was associated with higher postoperative FJS-12 values at short- to midterm follow-up, suggesting function more similar to that of a native knee. Residual postoperative laxity was associated with lower FJS-12 values in secondary exploratory analyses.

Humans

A standardised risk-stratified approach to the urological management of children with spina bifida.

BACKGROUND: The establishment of a multidisciplinary spina bifida (SB) clinic in 2006 resulted in a review of the literature and an audit of renal outcomes based on then management practices. The audit showed 17% new onset renal scarring over a mean 5.8-year follow-up period. This prompted the development of a local protocol based on risk stratification combining serial ultrasound and non-invasive bladder function assessments, with invasive urodynamic studies reserved for high-risk patients. OBJECTIVE: This study sought to assess the impact of a risk stratified protocol on renal scarring and continence outcomes in children with SB. METHODS: A single centre, retrospective case review of SB patients treated after the introduction of the protocol was conducted. Electronic medical records were used to access patient demographics, continence status and the results of investigations and adherence to the local management protocol. Management that deviated from the protocol was deemed non-adherence. Renal scarring was determined by the presence of scarring on DMSA renogram. Continence was defined as having no urinary incontinence or no more than a single episode of incontinence in a month in patients above the age of 5. For statistical analysis, descriptive statistics in percentages were used, for comparisons of dichotomous variables the Students t-test was performed and to calculate statistical significance a Fisher exact test was done. RESULTS: 167 SB patients were identified with a mean follow up of 56 months. 141 patients were considered adherent to the protocol, 26 were non-adherent. In the protocol adherent group 5 patients (3.5%) developed renal scarring compared with 6 patients (23%) managed out of protocol (p = 0.002). Overall, 49/108 patients were continent either self-voiding 8/108 (7%), with urethral CIC 19/108 (20%) and 22/108 (45%) of them required bladder augmentation. Urinary continence improved with age with 26% continence at age 10, 64% continence by age 15 and 90% continent above 15 years of age. CONCLUSION: A management approach based on risk stratification resulted in incidence of renal scarring that is better than historical controls and comparable to published outcomes. Social continence was achieved in 90% of SB patients by 15 years of age. Hostile bladder changes can be readily identified using non-invasive assessment methods. An expectant treatment approach based on risk stratification is associated with good long term renal outcome and utilises invasive urodynamic resources for SB patients at high risk of renal injury or to address urinary continence in the older child.

Humans

Impact of a thermal care bundle on peri-operative hypothermia, surgical site infection, and readmissions in osteosynthesis patients: A randomised controlled trial.

BACKGROUND: Maintaining normothermia throughout the peri-operative period prevents the occurrence of complications related to hypothermia. OBJECTIVE: To determine the effect of a thermal care bundle with a short prewarming period on inadvertent peri-operative hypothermia (IPH), surgical site infection (SSI), and unplanned readmission among osteosynthesis patients, and to identify associated variables. DESIGN: Open-label, randomised controlled trial. SETTING: University hospital. PATIENTS: One hundred and forty-eight patients who underwent osteosynthesis surgery. INTERVENTION: The intervention group received the thermal care bundle, which consisted in prewarming patients 10&#x200a;min before anaesthesia delivery and maintaining body temperature with a forced air device during surgery and the immediate postoperative period; in addition, the operating room environmental temperature was kept at 21&#x200a;&#xb0;C, and fluids were warmed to 38&#x200a;&#xb0;C. MAIN OUTCOME MEASURES: For the primary objective, hypothermia was defined as core body temperature below 36&#x200a;&#xb0;C and measured using the 3M Spot On zero heat flux sensor. Core temperature was recorded upon admission to the pre-operative holding area and subsequently every 30&#x200a;min until postanaesthesia care unit (PACU) discharge. Secondary objectives were SSI and readmissions: a follow-up at 30 to 60 and 90&#x200a;days was performed by the principal investigator. RESULTS: All 148 patients completed the study, and there were no significant differences between the groups at baseline. At the start of surgery, the incidence of hypothermia was significantly lower in the bundle group (1.3 vs. 9.9% among controls; odds ratio&#x200a;=&#x200a;7.59, P &#x200a;=&#x200a;0.021). A significantly lower incidence of hypothermia was also observed at admission to the PACU (14.3% in the bundle group vs. 29.6% among controls; odds ratio&#x200a;=&#x200a;2.07; P &#x200a;=&#x200a;0.024). Application of the bundle increased patients' core body temperature by 0.13&#x200a;&#xb0;C (95% confidence interval (CI), 0.003 to 0.254; P &#x200a;=&#x200a;0.045). Patients in the bundle group had a slightly lower observed incidence of wound infections requiring readmission (odds ratio&#x200a;=&#x200a;0.35; 95% CI, 0.04 to 2.92), although this difference was not statistically significant ( P &#x200a;=&#x200a;0.332). CONCLUSIONS: The bundle reduces peri-operative hypothermia by up to 59%, but does not affect on SSI; factors like presurgery hospital stay, operating room and PACU occupancy were identified as risk factors for SSI. REGISTRATION: 21 July 2022: NCT05469958 (Clinical Trials.gov), first recruitment 15 August 2022.

Adult