Journal of Clinical Medicine

Background Pediatric nephrotic syndrome (NS) significantly increases cardiovascular risk, primarily through activation of the renin-angiotensin-aldosterone system (RAAS) and chronic inflammation. This study aimed to evaluate the relationship between serum aldosterone and interleukin 6 (IL-6) levels with carotid intima-media thickness (CIMT) in children with steroid-sensitive (SSNS) and steroid-resistant NS (SRNS), both before and after combined treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). Materials and methods A prospective cohort study enrolled 32 children aged 2-18 years with idiopathic NS at Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia (May-June 2024). Participants received lisinopril (ACEI) or valsartan (ARB) for 12 weeks. Serum aldosterone was quantified via liquid chromatography-tandem mass spectrometry, IL-6 via electrochemiluminescence immunoassay, and CIMT via high-resolution B-mode Doppler ultrasound. Data were analyzed using SPSS version 26.0, including Shapiro Wilk normality testing, Pearson/Spearman correlations, and multivariate linear regression (enter method, R2=0.022), with statistical significance set at p<0.05. Results CIMT decreased significantly post-treatment (0.13{+/-}0.04 cm to 0.06{+/-}0.01 cm; p<0.001). Serum aldosterone remained stable (5.15 to 4.0 ng/dL; p=0.933), as did IL-6 (3.5 pg/mL; p=0.156). Univariate analyses revealed weak correlations (aldosterone-CIMT: R2=0.075; IL-6-CIMT: R2=0.215). Multivariate regression (R2=0.022) identified SRNS as positively associated with CIMT change (p=0.047), while aldosterone and IL-6 showed no significant independent effects. Conclusion This study highlights that ACEI and ARB therapy improved CIMT regardless of steroid sensitivity, suggesting vascular benefits may occur through pathways independent of aldosterone and IL-6 modulation.

Bilateral cochlear implantation (BCI) can improve spatial hearing in adults with bilateral hearing loss, but the early development of spatial hearing following sequential BCI remains poorly understood. This prospective longitudinal study investigated changes in spatial hearing experience in 23 adults undergoing sequential BCI, assessed before and at ~1, 3, and 8 months after bilateral implantation under two conditions: spontaneous and restrained head movements. Using a motion-tracking system combined with virtual reality, sound localization was assessed through absolute and signed errors, along with self-reported localization confidence and listening effort. Subjective spatial hearing was also assessed using the Speech, Spatial and Qualities of Hearing Scale (SSQ). Localization performance improved by 1 month after bilateral implantation, as evidenced by a reduction of absolute error and in the bias toward the first-implanted ear. Participants reported greater localization confidence and lower listening effort at 1 month, although these changes were not consistently maintained at later follow-ups. SSQ scores showed improved spatial hearing at 1 month, speech perception at 3 months, and sound clarity and discriminability at 8 months. Compared with head-restrained condition, accuracy and confidence improved when spontaneous head rotations were allowed. The temporal trajectories of localization bias, confidence, and effort were modulated by the duration of experience with the first CI. These findings indicate that changes in spatial hearing can emerge soon after second CI activation. They further highlight the contribution of spontaneous head movements and previous CI experience, and support the use of complementary measures to monitor the early development of bilateral listening.

Background: Growth differentiation factor 15 (GDF-15) has emerged as a prognostic biomarker in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Our study evaluated the temporal evolution of GDF-15 in the acute phase and its association with recurrent ischemic events. Methods: Serum samples were collected from patients with NSTE-ACS at admission and at 1 and 3 hours after admission. GDF-15 levels, along with other prognostic biomarkers, NT-proBNP and hs-cTnT, were measured. Spearman rank-correlation coefficients and linear regression models were used to identify the variables associated with GDF-15 levels at admission and with their temporal changes. Associations between GDF-15 and clinical outcomes were evaluated using Cox proportional hazards models. To assess incremental prognostic value, the areas under the curve (AUC) were calculated for each model. Results: GDF-15 levels showed a slight increasing trend within 3 hours of admission. The 1-hour change in GDF-15 was correlated with hs-cTnT changes. Increased 1-hour GDF-15 levels, compared with the admission levels, were associated with a higher risk of recurrent ischemic events during the 1-year follow-up (1.9% vs. 17.5%, P =0.019) and were an independent predictor after adjusting for established clinical variables and biomarkers (adjusted hazard ratio, 1.71 (1.28 to 228.75), P =0.03). Furthermore, serial measurements of GDF-15 provided additional prognostic information beyond traditional risk factors. Conclusions: Serial measurements of GDF-15 of NSTE-ACS patients provided independent and incremental prognostic value for predicting recurrent ischemic events. These findings support the potential utility of GDF-15 as a dynamic biomarker for early risk stratification in the acute management of NSTE-ACS.

ABSTRACT Background: The esophageal String Test (EST) is emerging as a minimally invasive alternative for assessing disease activity in eosinophilic esophagitis (EoE), yet the molecular composition of its protein content remains unknown. Objective: To comprehensively characterize the esophageal EST proteome, define an EoE-associated luminal protein signature, and evaluate its biological and clinical relevance. Methods: EST samples were obtained from patients with active EoE, healthy controls (C) and patients with gastroesophageal reflux disease (GERD). Label-free proteomic profiling was performed by liquid chromatography-tandem mass spectrometry. Differential protein accumulation, principal component analysis (PCA), pathway annotation, comparison with published esophageal tissue and salivary proteomes, receiver operating characteristic (ROC) analyses and correlations with clinical disease activity were performed. Results: More than 3,000 proteins were identified in esophageal EST samples. Global proteomic profiling clearly separated patients with EoE from both C and GERD, whereas only limited differences were observed between the latter two groups. This enabled the identification of an EoE-associated luminal protein signature comprising inflammatory, epithelial, and tissue remodeling proteins. Comparison with published proteomic datasets indicated that the EST samples a complex esophageal luminal protein microenvironment containing proteins represented in esophageal mucosa and saliva, together with inflammatory and extracellular components. Several individual proteins showed high discriminatory performance in this exploratory cohort for distinguishing EoE from non-EoE subjects, and multiple proteins correlated with eosinophil counts and endoscopic measures of disease activity. Conclusions: This study demonstrates that the EST provides access to a complex esophageal luminal protein microenvironment and establishes a molecular framework for its minimally invasive characterization in EoE. KEYWORDS: eosinophilic esophagitis, esophageal string test, esophageal luminal protein signature

Purpose: Videourodynamics (VUDS) are used to assess bladder dysfunction and risk of upper urinary tract deterioration in patients with spina bifida (SB), but interpretation is subject to interrater variability. Machine learning models have previously classified bladder dysfunction severity and predicted incident hydronephrosis using VUDS data. This study evaluated the performance of adapted versions of these models in an independent external cohort. Materials and Methods: VUDS data were collected from SB patients who underwent VUDS at a single institution between 2016 and 2025. Previously developed machine learning frameworks were adapted for implementation in the independent dataset. Three models were utilized: a deep learning convolutional neural network model using pressure-volume data, a deep learning imaging model using fluoroscopic imaging data, and an ensemble model that averaged the risk data from the pressure-volume and fluoroscopic data. The models were evaluated for prediction of incident hydronephrosis and classification of bladder dysfunction severity compared to expert pediatric urologist reviewers. Results: 70 patients were included in the hydronephrosis cohort, of whom 13 (18%) developed incident hydronephrosis. The ensemble model outperformed individual modalities, with a concordance index of 0.77 (pressure-volume only: 0.70, imaging only: 0.72) and an overall AUROC of 0.75 (pressure-volume: 0.67, imaging: 0.74). For bladder dysfunction classification in 95 VUDS studies, the ensemble model achieved 71% accuracy compared to 60% for pressure-volume data alone and 66% for imaging alone, with no substantial disagreements with expert reviewers. Conclusions: The machine learning models that were developed to predict incident hydronephrosis and classify the severity of bladder dysfunction using VUDS data were able to be adapted to an external, independent dataset and perform with similar discrimination and accuracy as previously reported.

Purpose: Stimulability testing involves the evaluation of multiple aspects of a patient's behavior, but the results are most frequently consolidated into a single domain (i.e., "stimulable"). The current study performs preliminary content, construct, concurrent, and predictive validation for the Multidimensional Stimulability Profile for Voice (MSP-V), a rating scale designed to measure multiple domains during stimulability testing (Degree of Change, Rapidity of Change, Generalization, Patient-rated Voice Quality, Patient-rated Voice Feel, and an overall rating of Stimulability Level). Methods: 78 patients with voice disorders (24 functional, 15 structural, 39 neurological) were administered the MSP-V by five speech-language pathologists (SLPs). Content validity was evaluated via the Content Validity Index (CVI) completed by nine voice-specialized SLPs. Construct validity was evaluated via exploratory factor analysis. Concurrent validity was assessed by determining whether MSP-V domains scaled in the expected direction compared to categorical stimulability ratings (e.g., "Highly stimulable" vs. "Stimulable"). Predictive validity was assessed by examining the relationship between MSP-V domains and voice disorder diagnosis, return to voice therapy, and patient-reported practice outside of therapy. Results: The CVI reached the critical value for clinician-rated and patient-rated domains. Two distinct factors were identified during EFA, one consisting of clinician-rated domains and the other of patient-rated domains. All MSP-V domains showed the expected directional relationships as categorical stimulability ratings. No domains differed significantly between disorder etiologies. The Rapidity of Change and Stimulability Level domains both significantly predicted return for voice therapy, where participants who rated lower on each domain were more likely to return to for voice therapy. No domains were predictive of patient-reported practice. Conclusions: The MSP-V is a clinically feasible tool with emerging content, construct, concurrent, and predictive validity that could be used to provide increased clarity and precision in stimulability testing documentation for research and practice.

BACKGROUND: Because of the high mortality rate associated with fulminant myocarditis (FM), there is limited evidence regarding the prognostic efficacy of endomyocardial biopsy (EMB). In this study, we aimed to evaluate the influence of EMB in the early phase after admission on treatment and prognosis in FM using a large-scale nationwide registry in Japan. METHODS: Patients with FM who required catecholamine or mechanical circulatory support between 2012 and 2017 from 235 hospitals across Japan were included. The primary outcome of death or heart transplantation within 90 days according to performance of early EMB were determined using Kaplan-Meier and Cox regression analyses. Factors associated with performance of early EMB, and subsequent medical treatment were analyzed. RESULTS: The median age of 736 patients with clinical FM was 56 years, and 407 patients (55%) received EMB. Most EMB (89%) were performed during the early phase (within 5 days of admission) and 63% were performed on the first day of admission. The prognosis of FM patients who underwent EMB was more favorable than that of those who did not based on the landmark analysis (log-rank test, P=0.04). Factor analysis demonstrated that FM patients who underwent EMB had a lower left ventricular ejection fraction, higher incidence of cardiogenic shock on admission, and higher rate of early mechanical circulatory support, as well as early initiation of corticosteroids and guideline-directed medical therapy (GDMT) for heart failure. Absence of any GDMT was associated with a less favorable prognosis on multivariate analysis (hazard ratio, 4.34 [95% CI, 3.14?6.01]; P<0.0001). CONCLUSIONS: Although performing EMB in the early phase after admission depends on disease severity in FM patients, it is associated with early initiation of advanced medical treatment and may contribute to improving the prognosis.

Objective: Dendritic cells (DCs) are priming local immune responses, and their tissue-associated activity increases in inflammatory conditions. In patients with coronary artery disease (CAD), circulating dendritic cell precursors (DCPs) are reduced. This study investigates circulating DCPs and tissue densities of migrated DCs in CAD patients undergoing bypass surgery, focussing on patients with chronic kidney disease (CKD) as a risk factor for CAD and a condition of chronic vascular inflammation. Approach and Results: Circulating DCPs were measured in the peripheral blood (before surgery) using fluorescence-activated cell sorting (FACS) in n=59 patients and results were compared with an age-matched healthy control group (n=45). DCs were stained (Fascin) in circular sections of the internal thoracic artery taken during bypass surgery and mature (CD83+) and immature (CD209+) DCs were differentiated. Cell densities were obtained digitally. Descriptive statistics and correlation analysis generated hypotheses. Circulating myeloid DCPs were reduced (p<0.001), concomitant CKD added no further reduction. Immature DCs were predominantly detected in the adventitia, mature DCs dominated in the intima (p<0.001). In CKD, reduced circulating myeloid DCPs correlated with immature DCs in the vessel wall (r=0.87; p=0.002) and rather mature DCs were detectable; in patients without CKD immature DCs were dominating. C-reactive protein correlated with mature DCs (r=0.38; p=0.026). Conclusions: Quantities of DCPs and mature and immature DCs vary between the vessel wall layers. The dominance of immature myeloid DCs in the adventitia suggests activation of the vascular-associated lymphoid tissue (VALT). Intensified inflammation associated with CKD may have promoted the maturation of myeloic DCs.

Incidence of ventilator-associated pneumonia (VAP) is increased in patients admitted for brain injury. Staphylococcus aureus appears to be a particularly common pathogen in these respiratory infections. Our aim was to confirm the extent of S. aureus involvement in VAP among patients with neurological injuries. We conducted a retrospective, multicenter study including patients with and without neurological injuries who developed VAP during their ICU stay. Among 15 702 patients admitted in the participant centers during the study period. 407 were finally included in the study. S. aureus was involved in 122 (61.6%) VAP in brain-injured patients and 63 (30.1%) of non-brain-injured patients. In brain-injured patients, multivariate analysis identified age (0.97 [0.95; 0.98]), antibioprophylaxis (0.31 [0.18; 0.53]; p < 0.0001), subarachnoid hemorrhage (2.18 [1.01; 4.68]; p=0.0461), lower Glasgow coma score (0.92 [0.87; 0.97]; p= 0.004) and SAPS II (0.98 [0.97; 1]; p=0.0174) as critical factors associated with the risk of S. aureus in VAP. In the non-brain-injured population, multivariate analysis identified antibioprophylaxis (0.38 [0.22; 0.65]; p=0.0006), age (0.96 [0.95; 0.98]; p<0.0001), SAPS II (0.98 [0.97; 1]; p=0.0265), thoracic surgery (0.21 [0.09; 0.48]; p=0.0002) and peripheral neurosurgery (1.95 [1.2; 3.19]; p=0.0076) as critical factors. A total of 172 patients (42.3%) died during their ICU stay and 90-days mortality was 194 (47.7%). No difference of mortality was noticed function of VAP-associated pathogen.

Objectives: To describe associations between peripheral arterial disease (PAD) and bladder health (BH) and lower urinary tract symptoms (LUTS) among a subset of women in the Coronary Artery Risk Development In Young Adults (CARDIA) study. Methods: Women from CARDIA at Birmingham, AL and Minneapolis, MN were eligible if they completed a questionnaire about bladder symptoms in 2022-23, an ancillary study post-year 35 called CARDIA-PLUS, including the global BH scale (possible range, 0-100) and the LURN-SI 10 (0-38) and the AUASI (0-35). A subset (n=216) completed an in-person examination, including the ankle brachial index (ABI) procedure (n=194). ABI scores were clinically categorized as normal (1.00-1.40), borderline abnormal (0.91-0.99), and abnormal (</=;0.90; evidence of PAD). Continuous BH and LUTS variables were regressed on ABI category, adjusting for sociodemographics, obstetric/gynecologic variables, co-morbidities, and physical activity. Key Results: Among women who completed BH/LUTS questionnaires and the ABI (n=192), the mean age was 63+/-4 years and racial composition was 47% Black and 53% White. ABI results were normal (74%), borderline abnormal (20%), and abnormal (6%). After adjusting for covariates, women with abnormal ABI scores had higher LURN-SI scores (4.1 points, 95% CI 0.7, 7.5) and did not have higher AUASI scores (1.4 points, 95% CI -3.1, 5.7) or lower BH scores (-9.6 points, 95% CI -24.0, 4.9) compared to women with normal ABI scores. Borderline abnormal ABI was not associated with BH or LUTS. Discussion/Conclusion: In this cohort, PAD was associated with greater LUTS severity. PAD and LUTS may share common etiologies and risk factors that need additional research.

BACKGROUND: Zinc inhibits energy production, growth, and proliferation in normal prostate cells while suppressing the malignant potential and angiogenesis that are essential to prostate cancer aggressiveness. The study aimed to determine the correlation of serum zinc with Gleason score as a marker for prostate cancer aggressiveness METHODOLOGY: We conducted a hospital-based cross-sectional analytical study carried out on forty-two (42) eligible participants with newly diagnosed histologically confirmed prostate adenocarcinoma over one year. Spearman's rank correlation was used to assess the relationship between serum zinc and prostate cancer aggressiveness as measured by the Gleason score. The impact of serum zinc level on the aggressiveness of severe prostate cancer was assessed using a binary regression model, adjusting for age as a confounder in the logistic regression model. A statistically significant P value was set at 0.05. RESULTS: The mean age of participants was 67.12 years, with a range of 45- 90 years. High-grade disease (Gleason 8) was the most common, representing 57.1% of patients. The median serum zinc concentration was 71.5 microgram/dL (IQ: 47.6 to 88.5 microgram/dL). Serum zinc and Gleason score showed a statistically significant inverse correlation (Spearman r = -0.514, p < 0.001). Reduced zinc levels were significantly associated with higher Gleason scores (MannWhitney; 140.0, p = 0.002). Low serum zinc independently predicted high-grade disease after adjusting for age. CONCLUSION: This study found a statistically significant inverse correlation between serum zinc concentrations and Gleason score in men with prostate cancer. This finding indicates that reduced serum zinc levels are associated with higher Gleason scores

Background: Temporomandibular disorders (TMDs) are common conditions in the general population. Several therapeutic approaches are available, but there is no consensus on the most effective, particularly in physiotherapy. Objectives: To assess the efficacy of manual therapy (MT) and therapeutic exercise (TE) in reducing pain in patients with TMDs. Methods: Four databases (MEDLINE, PEDro, EMBASE, CINAHL) were searched up to March 2025. We included randomized controlled trials (RCTs) evaluating the effects of MT and/or TE in individuals with TMDs, compared to any other rehabilitation treatment, with pain intensity as the primary outcome. The methodological quality was assessed using the PEDro scale. A network meta-analysis was performed to compare the effectiveness of different rehabilitative approaches. Results: 25 RCTs for a total of 1,540 people were included. The main comparisons were: MT and/or TE vs no treatment or placebo, occlusal splint, and instrumental physiotherapy. In most studies, MT and TE were more effective than controls in reducing pain. However, the network meta-analysis indicated that multimodal treatments were the most effective. The methodological quality of the included studies ranged from 3 to 9 points. Conclusion: MT and TE are effective strategies for reducing pain in subjects with TMDs and should be used as first-line interventions before more invasive treatments; the combination of dry needling and manual therapy appears to be the most effective approach. Nonetheless, the variability in study quality suggests that further high-quality research is needed to confirm these findings.

Frailty assessment is important while awaiting lung transplantation (LTx), as frailty is associated with disability and death before and after LTx. We assessed known risk factors and/or frailty indicators in frail, pre-frail, and non-frail patients according to the Short Physical Performance Battery (SPPB) and the Frailty Instrument for primary care of the Survey of Health, Ageing and Retirement in Europe (SHARE-FI), and evaluated the value of SHARE-FI as a proxy to detect frail patients. Frailty was assessed using SPPB and SHARE-FI in 82 patients on a waiting list for LTx. Demographic, anthropomorphic, and clinical variables were collected, and patients underwent respiratory/cardiorespiratory, biochemical, and quadriceps muscle performance assessments. The mean age was 57.3 {+/-} 9.4 years. Chronic obstructive pulmonary disease (COPD) (41.5%) and interstitial lung disease (ILD) (30.6%) were the most common indications for LTx. Four (4.9%), 13 (15.9%), and 65 (79.3%) patients were classified as frail, pre-frail, and non-frail by SPPB, respectively. These figures were 26 (31.7%), 41 (50%), and 15 (18.3%) with SHARE-FI. SPPB found differences between frail/pre-frail and non-frail patients in physical performance (6-minute walking distance) and muscular assessment, while SHARE-FI found differences in age, 6-minute walking distance, and oxygen saturation, and a trend in muscular strength. For COPD and ILD, frailty discrimination was better with SPPB. Concordance between the two measurements was weak, although all SPPB-frail ILD patients were detected by SHARE-FI. In patients awaiting LTx, SPPB showed better discrimination than SHARE-FI for COPD and ILD. SHARE-FI seems appropriate as a preliminary screening instrument for patients with ILD.

Abstract Background The SYNTAX score (SS) quantifies the severity and complexity of coronary artery lesions and serves as an independent predictor of major adverse cardiovascular events and mortality in patients with acute coronary syndrome (ACS). However, few studies have examined the association between SS and in-hospital cardiac arrest (IHCA) in this population. Therefore, this study aims to elucidate the relationship between SS and the incidence of IHCA in patients with ACS. Methods This study consecutively enrolled 3,224 patients undergoing percutaneous coronary intervention (PCI). Logistic regression and restricted cubic spline (RCS) analyses were employed to examine the association between SS and the incidence of IHCA. Participants were stratified into three groups based on SS: Group T1 (SS ? 10, N = 1,097), Group T2 (10 < SS ? 18, N = 1,089), and Group T3 (SS > 18, N = 1,038). The primary endpoint was the incidence of IHCA. Results The overall incidence of IHCA was 4% (N=147). After adjusting for covariates, SS was significantly associated with the incidence of IHCA in ACS patients treated with PCI (OR = 1.0400; 95% confidence interval (CI) = 1.0200?1.0700; p < 0.001). Compared with the T1 group, the T3 group exhibited an increased risk of IHCA (OR = 2.1800; 95% CI = 1.2900?3.6900; p = 0.0040). Subgroup analyses revealed that, after covariate adjustment, patients with ST-segment elevation myocardial infarction (STEMI) had an increased risk of IHCA (OR = 1.0700; 95% CI = 1.0300?1.1100; p < 0.001). Similarly, both patients with diabetes mellitus (DM) (OR = 1.0400; 95% CI = 1.000?1.0700; p = 0.0270) and those without DM (OR = 1.0600; 95% CI = 1.0200?1.1000; p = 0.0020) showed an increased risk. Furthermore, elderly patients (?60 years) (OR = 1.0300; 95% CI = 1.0100?1.0700; p = 0.0210) and non-elderly patients (<60 years) (OR = 1.0500; 95% CI = 1.000?1.1000; p = 0.0470) had an increased risk, as did male patients (OR = 1.0500; 95% CI = 1.0200?1.0700; p = 0.0020). RCS analysis indicated a dose-response relationship between IHCA incidence and SS (nonlinear p-value = 0.906), with the risk of IHCA increasing when SS exceeded 23.975. Incorporating SS into the baseline risk model improved the predictive value for IHCA incidence in ACS patients undergoing PCI (Net reclassification improvement [NRI]: 0.3537 [0.1906?0.5167], p < 0.001; Integrated discriminant improvement [IDI]: 0.0104 [0.0025?0.0183], p = 0.0097). Conclusions Among patients with ACS undergoing PCI, SS is significantly associated with the incidence of IHCA. Consequently, SS may serve as an effective predictor of IHCA in this population.

Background: Robot-assisted radical prostatectomy is the standard minimally invasive treatment for localized prostate cancer. Conventional multiport robotic surgery is widely applied yet associated with more abdominal trauma and postoperative discomfort. Single-port robotic surgery can further minimize surgical injury. The domestic KangDuo robotic system has been gradually used in urological oncology, but high-level prospective evidence comparing single-port and multiport extraperitoneal radical prostatectomy remains scarce. This trial aims to compare the efficacy and safety of these two surgical approaches. Methods: This is a single-center, prospective, 1:1 randomized, non-inferiority trial. Eligible patients diagnosed with cT1c-cT2cN0M0 localized prostate cancer will be randomized to receive either single-port (experimental group) or multiport (control group) extraperitoneal robotic radical prostatectomy using the KangDuo system. All participants will receive standardized enhanced recovery after surgery (ERAS) protocols. The primary endpoint is postoperative positive surgical margin rate. Perioperative parameters, postoperative recovery, medium-term functional recovery and oncological outcomes will be assessed comprehensively. Expected results: We hypothesize that the single-port approach is non-inferior to the multiport approach in terms of oncological radical effect. The single-port technique is expected to provide better minimally invasive benefits, with comparable perioperative safety, urinary/sexual function recovery and mid-term oncological outcomes between groups. Conclusions: This randomized trial will provide high-quality clinical evidence for the application of domestic single-port robotic surgery. The findings will facilitate individualized surgical selection for patients with localized prostate cancer. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2600125669 (http://www.chictr.org.cn/showproj.aspx?proj=2600125669).

Background: Robust evidence linking individual surgeon technical performance to patient outcomes in complex minimally invasive surgery remains scarce. Crowd-sourced video assessment offers a scalable alternative to expert review, but its clinical relevance in complex oncologic procedures such as robot-assisted minimally invasive esophagectomy (RAMIE) is unestablished. Methods: In this exploratory study, video recordings of 60 consecutive RAMIE procedures performed by 7 surgeons (2018-2023) were segmented into five representative surgical steps and rated by 93 blinded crowd-raters per segment using a modified GEARS instrument. Tertiles were used to compare top-performing operations and steps against the remaining two terciles for overall and step-specific performance, and associations with perioperative outcomes were analyzed. Results: Top-tercile overall performance was associated with significantly shorter operative time (abdominal, thoracic, and total) and less intraoperative blood loss (all p<0.05), without differences in postoperative outcomes. In exploratory step-specific analyses, top-tertile performance during infracarinal lymphadenectomy was associated with significantly fewer surgical complications (30.0% vs 60.0%; p=0.028), fewer severe surgical complications (25.0% vs 52.5%; p=0.043), and higher lymph node yield (22.8 vs 18.9; p=0.037), while the purse-string suture step showed the broadest operative-time benefit. These step-specific findings are hypothesis-generating and were not adjusted for multiple testing. Conclusion: Crowd-sourced video assessment enables scalable, step-specific evaluation of surgical performance in RAMIE associated with intraoperative blood loss and operative time. Exploratory analyses suggest that the relationship between technical performance and clinical outcomes might be step-specific, with infracarinal lymphadenectomy emerging as risky step linked to postoperative morbidity. These findings support further investigation of individualized performance assessment for quality improvement and risk stratification.

Background Postoperative nausea and vomiting (PONV) remains a frequent and distressing complication after gynecologic laparoscopic surgery, with residual incidence approaching 30-40% despite contemporary multimodal antiemetic prophylaxis. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique that activates auricular vagal afferents projecting to brainstem nuclei implicated in emetic reflexes. We present the protocol of a randomized trial to evaluate taVNS as an adjunctive, nonpharmacologic strategy to reduce PONV in this high-risk population. Methods This single-center, prospective, randomized, double-blind, sham-controlled, parallel-group superiority trial will enroll 146 adult women undergoing elective gynecologic laparoscopy under general anesthesia. Participants will be randomized 1:1 to active taVNS or sham stimulation, with stratification by Apfel risk score ([&le;]2 vs. [&ge;]3). Two 30-minute sessions will be delivered: one beginning 30 minutes before anesthesia induction and another 30 minutes after arrival in the post-anesthesia care unit. The primary outcome is the incidence of PONV within 48 hours postoperatively. Secondary outcomes include nausea severity (11-point numerical rating scale), time to first PONV episode, number of vomiting/retching episodes, rescue antiemetic use, postoperative pain intensity, cumulative opioid consumption (morphine equivalents), Quality of Recovery-15 scores at 24 and 48 hours, and gastrointestinal recovery indices. Analyses will follow intention-to-treat and per-protocol principles; missing data will be addressed via multiple imputation. Conclusions This trial aims to provide rigorous evidence on the efficacy and safety of perioperative taVNS for PONV prevention in women undergoing gynecologic laparoscopy. If proven effective, taVNS could be integrated into enhanced recovery after surgery (ERAS) pathways as a mechanistically grounded, nonpharmacologic adjunct to standard antiemetic regimens. Trial registration Chinese Clinical Trial Registry ChiCTR2600115965 (prospectively registered).

BACKGROUND Twin pregnancies have a two- to three-fold higher risk of preeclampsia (PE), but early prediction remains poor because current biomarkers and prediction models are largely derived from singleton pregnancies. Defining the biological changes that precede PE in twins may facilitate the development of more effective risk assessment approaches. OBJECTIVE We aimed to characterize maternal plasma protein changes preceding PE in twin pregnancies and to explore whether early circulating proteins could serve as improved risk stratification for twin PE. STUDY DESIGN We performed a nested case-control study within a prospective twin pregnancy cohort at Peking University Third Hospital. A total of 84 women with twin pregnancies were included, comprising 40 pregnancies complicated by PE and 44 normotensive controls. Longitudinal maternal plasma samples were collected in the first, second, and third trimesters. In the discovery cohort, maternal plasma proteins were profiled by mass spectrometry to identify trimester-specific protein changes associated with PE. Candidate proteins were then validated in an independent validation set. We further assessed the functional relevance of selected proteins in trophoblast and endothelial cell models and constructed prediction models integrating biomarkers with maternal clinical characteristics. RESULTS Twin pregnancies complicated by PE showed distinct trimester-dependent protein alterations, with first- and second-trimester changes mainly involving immune regulation and glycolipid metabolism, and later changes enriched in cardiovascular-related pathways. Several proteins demonstrated early discriminatory patterns, including increased annexin A3, chitotriosidase-1, and ferritin light chain (FTL), together with decreased annexin A2 in the first trimester, whereas the conventional singleton markers (sFlt-1 and PAPP-A) did not differ. ELISA validation of these candidate biomarkers yielded an AUC of 0.93 for twin preeclampsia prediction; integration with standard maternal clinical factors further improved discriminatory performance to an AUC of 0.97. Accordingly, a multivariable model combining annexin A2, annexin A3, chitotriosidase-1, FTL, and maternal clinical factors achieved strong internal performance for early discrimination of PE in twin pregnancies (AUC, 0.97; 95% CI, 0.93-1.00). Moreover, annexin A2 knockdown impaired trophoblast migration and invasion and reduced inflammatory cytokine secretion in endothelial cells, supporting a role in placental development and maternal vascular adaptation. CONCLUSION Twin pregnancies that later develop PE exhibit early and progressive maternal plasma protein alterations that can be detected before clinical disease onset. These findings identify candidate biomarkers and biologically relevant pathways that may help explain why PE in twins differs from singleton disease and may support future twin-specific risk stratification strategies. These results require external validation before clinical application.

Background. Information is lacking about everyday psychological states of individuals with a recent myocardial infarction (MI) and whether they influence outcomes. We investigated real world psychological experiences and their association with subsequent cardiovascular events in survivors of an MI. Methods. We studied 287 individuals [&le;] 60 years of age within 8 months from an MI. At the baseline visit, we assessed sociodemographic and clinical factors, and administered a battery of psychological scales of depression, anxiety, anger, perceived stress and social support. Participants underwent a 7-day home monitoring of mood and stress using ecological momentary assessments, and a momentary negative affect (MNA) score, integrating daily mean ratings of sadness, anxiety, anger, distress and loneliness, was calculated. Participants were followed for a median time of 28 months. The study endpoint was a composite index of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal MI, stroke or hospitalizations for heart failure. Cox proportional hazards models adjusted for sociodemographic and clinical factors. Results. The mean age of the sample was 51 years, and 43% of participants were women. Each standard deviation increase in MNA was significantly associated with a 60% increased risk of MACE (95% confidence interval (CI), 20% to 100%), irrespective of adjustment for sociodemographic factors and clinical characteristics. The association was similar in women and men. Momentary positive mood and momentary perceived stress were not associated with MACE. The MNA score showed a larger independent contribution to MACE compared to the combined battery of baseline psychological assessments and the association was independent of baseline history of depression. Conclusion. Among individuals after MI, moment-to-moment negative affect during one week of monitoring in daily life is a powerful predictor of subsequent cardiovascular events. A prospective evaluation of negative mood during everyday living could represent a novel strategy to uncover residual risk after MI.

Background: The systemic immune-inflammation index (SII) is a routinely available blood-derived marker with potential prognostic relevance after coronary artery bypass grafting (CABG). We evaluated associations between preoperative SII and postoperative outcomes. Methods: PubMed, Embase, Scopus and Web of Science were searched to 1 October 2026, with supplementary searches through 14 October 2026. Peer-reviewed observational studies evaluating preoperative SII in adults undergoing CABG were eligible. Methodological quality was assessed using the Newcastle-Ottawa Scale. Compatible categorical associations and exploratory adjusted continuous mortality effects were pooled separately using restricted maximum-likelihood random-effects models; other findings were summarized descriptively. Results: Thirty-one reports were included, with an aggregate sample of 30,976 and possible cohort overlap; five contributed to meta-analysis. Two off-pump cohorts comprising 1,378 patients and 180 atrial-fibrillation events yielded an imprecise crude association with postoperative atrial fibrillation (OR 1.60, 95%CI 0.53-4.82; I2=68%). An exploratory crude synthesis indicated greater intra-aortic balloon pump use with higher SII (OR 2.45, 95%CI 1.16-5.18; I2=51%). Two cohorts with differing follow-up yielded an exploratory adjusted mortality HR of 1.11 (95% Wald CI 1.05-1.18) per study-specific SD increase in log-SII. In one 624-patient cohort, high SII was associated with postoperative acute kidney injury after adjustment (OR 3.35, 95% CI 2.25-4.97).Apparent atrial-fibrillation discrimination varied (AUC 0.587-0.946). Conclusions: Preoperative SII showed associations with selected adverse outcomes after CABG, supporting further evaluation as an accessible prognostic marker. Its incremental value beyond established clinical risk models requires validation. Keywords: Systemic immune-inflammation index; Coronary artery bypass grafting; Atrial fibrillation; Prognosis; Systematic review