Journal of Clinical Medicine

Background. The optimal anesthetic strategy for mechanical thrombectomy remains contested; clinical trials and meta-analyses yield conflicting results. Emerging evidence has shown stress hyperglycemia ratio (SHR) to be among the strongest independent predictors of poor thrombectomy outcomes. General anesthesia (GA) is known to provoke a more pronounced neuroendocrine stress response than procedural sedation, yet no prior study has investigated perioperative glucose dynamics between GA and sedation in thrombectomy patients. Methods. Using the TriNetX federated research network, we conducted a retrospective propensity score-matched cohort study of non-diabetic adults undergoing mechanical thrombectomy for anterior circulation acute ischemic stroke under GA versus sedation. After propensity score matching 2,556 matched pairs remained. Results. At the population level, mean glucose divergence was modest in absolute terms (Day 0: 110.90 vs 106.77 mg/dL; ? = 4.13 mg/dL; p = 7.82 x 10-11; Day 1: 107.69 vs 103.25 mg/dL; ? = 4.44 mg/dL; p = 8.16 x 10-14). GA conferred an 83.2% relative risk increase to severe-range hyperglycemia, defined as blood glucose > 181 mg/dL on the day of the index procedure (Day 0: RR = 1.832, 95% CI 1.457 ? 2.303; NNH: 29), with effects persisting on day 1 following the thrombectomy (Day 1: RR = 1.66, 95% CI 1.228 ? 2.249). GA patients received significantly more exogenous insulin on both days 0 (GA: 21.24%, Sedation: 17.23%, RR = 1.231, p = 2.96 x 10-4) and day 1 (GA: 11.3%, Sedation: 8.69%, RR = 1.30, p = 0.00178). All primary outcomes survived Bonferroni correction. Conclusion. General anesthesia is strongly associated with persistent hyperglycemia following mechanical thrombectomy in non-diabetic patients. These findings identify anesthesia-modality as a potential modifiable risk and provides a mechanistic hypothesis in the ongoing GA versus CS debate for thrombectomy. Future glucose management protocols may need to be tailored to anesthetic strategy.

Background: Sleeve gastrectomy is the most frequently performed bariatric procedure worldwide but is associated with the development of de novo gastroesophageal reflux disease (GERD). Hiatal hernia has been identified as a relevant anatomical factor in postoperative reflux, although most studies evaluate it dichotomously without analyzing whether its size influences GERD risk. The aim was to evaluate the association between preoperative hiatal hernia size and de novo GERD after sleeve gastrectomy. Methods: Retrospective, single - center, observational study of patients undergoing sleeve gastrectomy at Hospital Central Norte de Petroleos Mexicanos (2018 - 2025). Demographic and clinical characteristics, endoscopic classification of hiatal hernia size (small <2 cm, medium 2.1 - 4 cm, large >4 cm), and evidence of de novo GERD were analyzed using descriptive statistics, Fisher's exact test, odds ratio (=R) estimation with 95% confidence intervals (CI), and binary logistic regression. Statistical significance was set at p<0.05. Results: Fiftysix patients were included (mean age 48.3 {+/-} 8.1 years; 67.9% male). Hiatal hernia classification was conclusive in 46 patients (82.1%): 63.0% no hernia, 4.3% small, 30.4% medium, and 2.2% large. De novo GERD occurred in 14.0% of patients without preexisting GERD (6/43). No significant association was found between hiatal hernia size and de novo GERD (Fisher p=0.515). In the reduced logistic model, neither hiatal hernia (medium/large vs. absent/small; OR 3.47; 95% CI 0.50 - 29.43; p=0.207) nor age (OR 1.02; 95% CI 0.90 - 1.13; p=0.754) was significantly associated. No evaluated factor (sex, smoking, alcohol, age) reached significance. Conclusions: In this cohort, no statistically significant association was demonstrated between preoperative hiatal hernia size and de novo GERD after sleeve gastrectomy; however, the low number of events limits the ability to exclude a clinically relevant association. These findings are compatible with a multifactorial mechanism rather than with the isolated presence of this finding. Prospective studies with larger sample sizes and standardized reflux assessment instruments are required to confirm these results.

Objectives: Speech outcomes with cochlear implants (CIs) vary widely across patients and remain difficult to predict from pre-operative data. This study addressed three questions with clinical relevance: (RQ1) Can AI models predict individual CI speech outcomes, and if not, why? (RQ2) Can pre-operative data be used to identify patients at risk of poor outcomes? (RQ3) Do post-operative speech scores early after implantation contain prognostic information for later speech outcomes? Design: A retrospective analysis was performed using data from a single centre contributing to the Swiss National Cochlear Implant Database (N = 771 patients; 473 adults after exclusion of single-sided deafness). For RQ1, pre-operative data and seven prediction methods, from standard linear regression to recent machine-learning models, were used to predict post-operative word recognition scores. Prediction models were assessed on held-out data and on data from patients implanted later than the cohort used for model training. For RQ2, the best-performing model under RQ1 was used to predict patients with a poor outcome after implantation (word-recognition score below 40%), and pre-operative variables were grouped by clinical type to identify sources of information for risk prediction. For RQ3, the prognostic value of early post-operative speech measurement was assessed by adding six-month post-operative word scores to the pre-operative data and a clustering analysis was performed to identify distinct trajectories post implantation. Results: Cross-validated R2 for individual CI speech score prediction was small across all algorithms (best model with full feature set: R2 = 0.22) and conformal prediction intervals spanned +/- 41 percentage points, covering nearly the whole range of possible scores. Speech score distributions of patient groups defined by audiometric, aided-field and pre-operative speech variables converged after implantation (mean distance between group distributions decreased from 21.5 to 6.0 percentage points), while distributions of groups defined by developmental and communicative variables diverged. Pre-operative speech scores were much better predicted from pre-operative variables (R2 = 0.48 based on audiometric data only). For risk prediction, the best-performing model identified poor outcome with AUC = 0.71. Self-rated articulation was the dominant pre-operative predictor. Audiometric, aided-field, and pre-operative speech data on which other prediction models have relied classified poor outcome at chance (AUC = 0.53), whereas developmental and communicative variables performed better (AUC = 0.65). Adding the six-month post-operative word score to the pre-operative data substantially raised R2 for long-term outcome from 0.03 to 0.48. Four trajectory types (Early Responders, Late Responders, Non-Responders, and Decliners) emerged from the clustering analysis but were not predictable from pre-operative data. Conclusions: The limited prediction performance for CI speech outcomes appears to be a property of the pre-operative data rather than of the prediction methods applied to them. However, pre-operative data can partially identify patients at risk of poor outcome. Importantly, speech data obtained within six months after implantation significantly improves outcome prediction at later time points. Longitudinal assessments post implantation therefore have potential for clinical intervention to improve long-term CI outcome. These findings support a two-stage framework for clinical translation: data-based risk counselling before surgery and post-operative monitoring for selective intervention after surgery.

Atypical sensory processing is common in attention-deficit/hyperactivity disorder (ADHD), yet decreased sound tolerance has received little attention, and it remains unclear whether it reflects actual auditory sensitivity or a vulnerability to attentional breakdown under acoustic load. The only prior study provided a single overall estimate, unable to separate sensory symptoms such as avoidance and distress from attentional and fatigue-related difficulties under noisy or demanding conditions. Here, we examined whether parent-reported auditory difficulties in children with ADHD are uniform or concentrated within specific symptom domains, and whether they vary with clinical presentation or medication. A total of 226 children (ages 6-12; 162 with ADHD, 64 typically developing controls) were assessed using the parent-report adaptation of the Khalfa Hyperacusis Questionnaire (Turkish version). The ADHD cohort was stratified by medication status and clinical presentation, and total, subscale, and item-level scores were compared across groups. Our findings show that children with ADHD scored higher than controls on the total and hyperacusis-effects subscale, but not on the coping subscale. Only four of the eleven items distinguished the groups, all reflecting concentration in noise or its decline under fatigue; no item reflecting sound avoidance, sensitivity, or distress differed between groups. This pattern was independent of clinical presentation, medication, and age; it persisted after adjustment for parental education. These results suggest that elevated auditory difficulties in ADHD are better explained by attention- and fatigue-related vulnerability than by heightened auditory sensitivity and may warrant environmental rather than audiological interventions.

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.

Objectives: To assess how patients with non-valvular atrial fibrillation (NVAF) receiving oral anticoagulants are managed in routine primary care practice in Spain. Methods: This observational, descriptive study included patients with NVAF treated with oral anticoagulants for at least 6 months before enrolment and managed in primary care settings in Spain. The Barthel and ACTS questionnaires were administered to evaluate functional autonomy and treatment satisfaction, respectively. Results: A total of 1,901 patients were included: 428 received vitamin K antagonists (VKAs) and 1,473 direct oral anticoagulants (DOACs). Compared with patients receiving DOACs, those treated with VKAs were significantly older and had a higher prevalence of more hypertension. Mean treatment duration was 7.6 years for VKAs and 3.8 years for DOACs. Among patients receiving VKAs, 56.2% and 59.0% achieved good anticoagulation control according to the direct and Rosendaal methods, respectively. Patients in the DOAC group reported greater satisfaction across several domains, including perceived treatment benefits, lower impact on daily life, and overall positive treatment effect. Event incidence rates (per 1,000 person-years) were higher with DOACs than with VKAs for stroke (1.75; 95% CI 1.05-2.92), ischemic stroke (1.78; 95% CI 1.06-3.00), acute myocardial infarction (1.64; 95% CI 0.97-2.79), and major bleeding (3.68; 95% CI 1.81-7.46). Conclusions: In routine primary care practice in Spain, patient profiles and treatment duration varied by oral anticoagulant type. These differences may partly explain the higher rates of stroke and major bleeding observed with DOACs versus VKAs, despite greater treatment satisfaction among patients receiving DOACs.

Background Bethesda III thyroid nodules remain diagnostically indeterminate, and intraoperative frozen section is used selectively to support surgical decision-making. Its value in this specific cytological category is uncertain because a malignant result may be highly specific while non-malignant and non-definitive results may fail to exclude cancer. Objective To estimate the sensitivity and specificity of intraoperative frozen section for detecting malignancy in thyroid nodules with preoperative Bethesda III cytology. Methods The protocol was prospectively registered in PROSPERO (CRD420261416683). A systematic review was conducted in PubMed, Embase, Web of Science, Europe PMC, and the Cochrane Library. Studies were eligible when they reported a separable Bethesda III cohort, intraoperative frozen-section findings, and final histopathology. Frozen section was classified as positive only when malignancy was reported. Benign, suspicious, indeterminate, deferred, inconclusive, and follicular-pattern results were classified as non-malignant. Study-level 2 x 2 tables were synthesised with random-effects logit models. Because all studies reported zero false-positive results, a full bivariate model with freely estimated covariance was not identifiable; a pseudo-bivariate HSROC approximation was therefore used. QUADAS-2 was used for risk-of-bias assessment. Results Ten studies comprising 1,069 Bethesda III patients or nodules were included. The pooled sensitivity was 43.1% (95% CI, 21.3-67.9) and the pooled specificity was 98.8% (95% CI, 97.0-99.5). Sensitivity was highly heterogeneous (Q = 83.45, I2 >90%, T2= 2.15), whereas specificity showed negligible between-study variance. Excluding Mao 2023 reduced pooled sensitivity to 35.6% (95% CI, 23.8-49.5) and reduced sensitivity heterogeneity to moderate levels (Q = 12.44, I2 = 36%, T2 = 0.25); specificity remained 98.7% (95% CI, 96.7-99.5). The approximate HSROC AUC was 0.89 including Mao 2023 and 0.87 excluding Mao 2023, but these values were driven largely by the uniformly high specificity. Conclusions Intraoperative frozen section in Bethesda III nodules has excellent specificity but limited and variable sensitivity. It is more suitable as a rule-in test than as a rule-out test. A non-malignant or non-definitive result should not be used alone to exclude malignancy or determine the extent of thyroid surgery.

Introduction. Hypertrophic cardiomyopathy (HCM) is characterized by clinical and genetic heterogeneity. Age of manifestation, clinical and anatomical phenotypes of HCM vary significantly. This study discusses genetic causes and reconstructive surgery results for patients with particular intracardiac phenotype - diffused generalized HCM (DG-HCM). Methods: personal and familial medical history, general examination, 12-lead resting ECG, 24-hour ECG Holter monitoring, transthoracic and transesophageal EchoCG, cardiac MRI with gadolinium enhancement. A ten-gene panel was sequenced by IonTorrent PGM. Mutational screening in patients with suspected multisystemic diseases was performed by Sanger sequencing. Results: 170 patients with obstructive HCM (oHCM) requesting genetic counseling and surgical correction of HCM were evaluated. We distinguished particular DG-HCM subtype of oHCM (diffuse hypertrophy of IVS, LV free walls, papillary muscles displaced towards the LV apex) in 34 patients; 31 out of 34 underwent open heart reconstructive surgery. Patients with DG-HCM were younger at the time of surgery, had higher risk of SCD, and connective tissue dysplasia of the mitral valve. Hemodynamics normalization was observed in 1, 3, and 5 years after surgery. Eighteen ICDs were implanted; five patients experienced appropriate shocks. The genetic spectrum was enriched up to 30% by multisystem disorders. Mutations in "sarcomeric" genes were detected in 15%. Conclusion: Intracardiac phenotype of HCM may correlate with genetic cause and long-term prognosis. DG-HCM phenotype accounts for 20% oHCM patients and indications for open-heart surgery. Extended myectomy with parietal resection of papillary muscles and correction of mitral valve insufficiency provides long-term benefits for DG-HCM patients. Multisystem disorders in patients with DG-HCM should be of special attention. Study was supported by research project FURG-2024-0004.

Background: Olfactory dysfunction is a recognised but poorly characterised comorbidity of Primary Ciliary Dyskinesia (PCD). No prior systematic review has synthesised its prevalence or clinical correlates. Methodology: A PRISMA compliant systematic review and meta-analysis was conducted. Five databases were searched to February 2026. Observational studies reporting olfactory function in confirmed PCD were included. Risk of Bias was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis using the Freeman-Tukey double arcsine transformation was performed to calculate pooled prevalence with 95% confidence intervals (CI) and prediction intervals (PI). Results: Twelve studies (n=865) were included. Overall pooled prevalence of olfactory dysfunction was 43.4% (95% CI 25.2-62.5%; 95% PI 0.1-99.0%). Objective psychophysical testing yielded a significantly higher pooled prevalence of 66.1% (95% CI 55.5-76.0%; 95% PI 38.4-88.9%) compared to patient-reported outcome measures (30.5%; 95% CI 11.4-54.0%). Older age, greater sinonasal disease burden, and specific ciliary ultrastructural defects were associated with worse olfactory function. A striking discordance between objective dysfunction and subjective awareness was observed across multiple studies. Conclusions: Olfactory dysfunction is highly prevalent in PCD and substantially under-recognised by patients. Routine objective olfactory screening should be integrated into standard multidisciplinary PCD care.

Background: Early access to pregnancy assessment units now detects many tubal ectopic pregnancies (TEP) at a stage when they could resolve spontaneously, creating a management dilemma. Methods: We performed a hypothesis-generating exploratory analysis in a retrospective study to assess whether serum progesterone (P4) levels in women with TEP are associated with management outcome. Results: Ninety-one cases of TEP managed in a single centre over three years were analysed. Receiver operating characteristic (ROC) curve analysis was used to explore serum levels of progesterone (P4), first human chorionic gonadotropin (hCG) and peak hCG (alone and in combination) in relation with successful completion of expectant management. Decision-tree analysis using first hCG and P4 was additionally performed to explore clinical sequential risk stratification. 23% (n=21) successfully completed expectant management. P4 concentrations in the expectant management group (median 3 nmol/L, IQR 2.00 to 8.50) were significantly lower than in those requiring surgical or medical management (median 17 nmol/L, IQR 5.75 to 29.25; p=0.0002). Area under the ROC curve (AUC) values for P4, log10 first hCG, log10 peak hCG and P4 with log10 first hCG were 0.766, 0.814, 0.811 and 0.835, respectively, for predicting successful expectant management. However, hCG was not significantly outperformed. Nonetheless, Youden optimised thresholds for hCG and P4 are reported, alongside decision-tree analysis that identified sequential first hCG and P4 thresholds associated with successful expectant management. Conclusion: Lower P4 levels are associated with successful expectant management of TEP but they do not outperform hCG either alone or as an adjunctive marker.

Background: Acute pulmonary embolism (PE) is a major cause of cardiovascular morbidity and mortality. This study aims to describe the epidemiological trends, clinical complexity, and in-hospital mortality of PE admissions in Spain from 2022 to 2024. Methods: We conducted a nationwide, retrospective study using the Spanish Minimum Basic Data Set for Hospitalization (MBDS-H) for adult patients admitted with acute PE. Results: We identified 125,305 hospital admissions for acute PE. The median patient age was 74 years with a slight male predominance (51-52%). A high comorbidity burden was observed: 61-62% had COPD, 35-37% hypertension, and 21-24% malignancy; ICU admissions increased from 11% to 13% (p < 0.001), with median ICU stay rising from 4 to 7 days (p < 0.001). In-hospital mortality significantly decreased during 2022-2024 from 13.12% to 11.44% (p = 0.013). Mortality per 100,000 inhabitants was consistently higher in men. Conclusion: This study highlights the high healthcare burden posed by acute embolism in hospitals, demonstrating an increase in patient complexity alongside a decline in overall mortality.

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.

Objective: To evaluate the rate, timing, and predictors of additional therapy among women with idiopathic overactive bladder (OAB) following initial minimally invasive treatments (MIT). Study Design: Retrospective single center cohort study of women with idiopathic OAB treated between 2012 and 2021. Using ICD and procedural codes, we identified women who underwent posterior tibial nerve stimulation (PTNS), sacral neuromodulation (SNM), or intradetrusor onabotulinumtoxinA (BTX). The primary outcome was receipt of additional OAB treatments,OAB medication initiation or a different MIT. Kaplan-Meier analysis estimated time to additional therapies; Cox proportional hazards and random survival forest models identified predictors. Results: 1,007 women were included (PTNS: 459; SNM: 192; BTX: 356). At three years, 75% of PTNS patients, 58% of BTX patients, and 40% of SNM women required additional therapies with most patients choosing additional pharmacotherapy rather than crossover to a different MIT. Median time to additional treatments was 10 months (PTNS), 19 months (BTX), and 53 months (SNM). Higher BMI was associated with increased risk of further treatment after SNM (HR 2.1, 95% CI: 1.1-4.2), while recurrent urinary tract infections were associated with needing additional therapies in the BTX cohort (HR 1.8, 95% CI: 1.1-3.2). Random survival forest models resulted in poor model performance. Conclusions: Following initial MIT for idiopathic OAB, many women required additional treatment within three years, many choosing pharmacotherapy rather than transition to another MIT.

Objective: To test the hypothesis that body mass index (BMI) replaces sex as the core risk factor for cholecystitis in plateau populations, and to characterize the true risk factor profile of gallstone patients at high altitude. Methods: A single-center retrospective cohort study included 605 elective laparoscopic cholecystectomy patients at Qinghai Red Cross Hospital (2,260 m; 2020-2023), categorized into simple gallstones (n=434) and gallstones with cholecystitis (n=171). Univariate analysis, multivariate logistic regression, nested model comparison, interaction analysis, and sensitivity analyses were performed. All statistics were independently recomputed using Python 3.11 and cross-validated against original statistical deliverables. Results: The original hypothesis was falsified. The cohort had a mean age of 43.7+/-11.8 years, BMI of 24.2+/-3.8 kg/m^2, female-to-male ratio of 2.10:1, and SBP of 117.4+/-15.8 mmHg. Multivariate logistic regression (adjusting for age, BMI categories, sex, SBP, and DBP) showed that SBP was the only significant positive predictor (OR=1.027/mmHg, 95%CI: 1.008-1.047, P=0.005), while BMI overweight (OR=1.038, P=0.856) and obesity (OR=0.645, P=0.137) were non-significant, as was sex (OR=0.814, P=0.322). Age showed a significant negative association (OR=0.978/year, P=0.007), constituting an "age paradox" with younger patients having higher cholecystitis rates (<30 years: 36.8% vs >=60 years: 25.0%; Spearman rho=-0.087, P=0.032), which may reflect selection bias or plateau-specific mechanisms. Nested model comparison showed that adding blood pressure to the classical model (age+BMI+sex, AUC=0.575) significantly improved discrimination (AUC=0.615, DeltaAUC=+0.040, 95%CI: +0.007 to +0.084; LR chi^2=8.19, P=0.017). SBP was non-significant in univariate analysis (OR=1.005, P=0.346) due to a suppression effect: age was a negative confounder, simultaneously increasing SBP and decreasing cholecystitis risk, thereby masking the true SBP effect. Conclusion: The risk weight of cholecystitis is remodeled in the plateau hypoxic environment, but in a direction opposite to the original hypothesis: SBP is the only significant positive predictor (P=0.049 in the SBP-only recommended model), while BMI and sex are non-significant, and age shows an inverse association. Blood pressure management should be integrated into the risk stratification system for plateau cholecystitis. The original hypothesis that BMI replaces sex is explicitly falsified.

Introduction Individuals with Gastroesophageal Reflux Disease (GERD) often experience airway inflammation and bronchoconstriction as a result of reflux aspiration and/or vagally mediated reflexes. The Impulse Oscillometry System (IOS) is a sensitive, non-invasive tool that can detect subtle changes in airway resistance. While there are few studies exploring airway resistance in GERD globally, no studies have been conducted in Sri Lanka. Therefore, we aim to compare the airway resistance using IOS in medical undergraduates with and without symptomatic GERD. Methods A cross-sectional study was conducted among 811 medical undergraduates (31.1% male; mean age 22.9 years) at the Faculty of Medicine, Rajarata University of Sri Lanka. Symptomatic GERD was screened using the validated GerdQ, and a cutoff of[&ge;]8 was used to diagnose those with GERD symptoms. Of the 242 (29.8%) with GERD symptoms, 188 with chronic respiratory diseases or recent respiratory symptoms were excluded, and 50 with GERD symptoms and 50 healthy, age- and sex-matched controls were recruited. Lung function was assessed using IOS and spirometry, according to American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines. Results Prevalence of symptomatic GERD among medical undergraduates was 29.8% (242/811). The common symptoms among GERD were heartburn (89.6%, 217/242) and regurgitation (85.5%, 207/242). Oscillometry parameters including, R5-R20 Hz (15.29% vs 9.69%, p=0.002), Fres (14.95 1/s vs 13.37 1/s, p = 0.04), and AX (0.66 vs 0.48, p = 0.02) were significantly higher in students with symptomatic GERD (mean = 15.29%) than in healthy controls (mean = 9.69%; p = 0.002). However, spirometry parameters including FEV1, FVC, and PERF did not differ between the GERD-positive and control groups. Conclusion Individuals with symptomatic GERD demonstrated a higher peripheral airway resistance compared to controls, whereas no significant difference was observed in upper airway resistance. This could be due to the gastric acid stimulation of vagal nerve terminations in the lower part of the esophageal wall, leading to increased resistance in the peripheral airways through vagally mediated bronchoconstriction.

Objectives: The purpose of this pilot study was to investigate (1) if the Speech Intelligibility Index (SII) could be used to identify ears that meet cochlear implant (CI) candidacy beyond the "60/60" referral guidelines and (2) investigate the relationship between SII from patients' own hearing aids (HAs) and SII from optimally fit clinic-stock HAs such that a patient's own HAs can act as a proxy for an optimally fit HA and thus as a referral metric. Design: Prospective study of 23 participants ([&ge;] 18 years) with bilateral moderate to profound sensorineural hearing loss who were CI candidates in at least one ear. SII-Clinic (SII-C) values were recorded with probe-microphone measures using a Verifit II device (NAL-N2 targets) with speech stimuli presented at 60 dB A during patient CI evaluation in either their own HAs or clinic-stock HAs. SII values from participants' own HAs were recorded as part of a larger research protocol, thus SII-Personal (SII-P), with probe-microphone measures using a Verifit I device (NAL-RP targets) with pink noise stimuli presented at 65 dB A. Participants that did not wear HAs did not have SII-P calculated. Data was collapsed across ears. Correlation analysis between SII and best-aided consonant-nucleus-consonant (CNC) was conducted. Benchmark SII values were extrapolated using a best-fit line and CI candidacy rates reflecting various aided CNC scores that could be applied across CI centers. Nested logistic regression models were used to determine if the SII-C could improve model fit beyond the revised ear-specific 60/60 referral guideline. The relationship between SII-C and SII-P was assessed with Wilcoxon signed-rank test and Spearman correlation. Results: Correlation between SII-C and aided CNC score was r = 0.82 (p < 0.001), and the correlation between SII-P and aided CNC was r = 0.46 (p = 0.014). Extrapolated benchmarks of SII were calculated based on different CNC candidacy cutoffs, and benchmarks were able to capture at least 83% of the ears that met CNC candidacy cutoffs. SII was also found to improve model fit with word recognition score (WRS) and pure tone average (PTA) for 60% CNC candidacy cutoff ({chi}2 = 9.7; p = 0.002) and increased discrimination (AUC = 0.89 to AUC = 0.99). There was no significant difference between SII-C and SII-P using the Wilcoxon signed-rank test (p = 0.559). Conclusions: A larger study is needed that includes more ears that do not qualify for a CI; however, the results of this study demonstrate that (1) SII has the potential to be used in conjunction with the 60/60 referral guideline for CI candidacy evaluations and (2) SII can be used as a marker of audibility across different devices, including patients' own HAs, making SII an accessible metric during HA fittings and fine tunings.

Background: Early identification of complicated appendicitis is essential for appropriate management, yet accurate preoperative risk stratification remains challenging. Whether objective laboratory-based models can achieve predictive performance comparable to models incorporating clinical findings remains unclear. Objective: To compare clinical, laboratory-based, and combined clinical-laboratory prediction models for complicated appendicitis and to evaluate the incremental value of the Prognostic Nutritional Index (PNI). Methods: This retrospective study included 1,132 consecutive patients with acute appendicitis. Cases were classified as uncomplicated or complicated appendicitis based on pathological findings and imaging. Three multivariable logistic regression models were developed: a clinical model (Model A), a laboratory-based model (Model B), and a combined clinical-laboratory model (Model C). Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC), and AUCs were compared using DeLong's test. Results: Complicated appendicitis was identified in 341 patients (30.1%). Higher C-reactive protein, higher neutrophil percentage, and lower PNI were independent predictors of complicated appendicitis. The AUCs were 0.791 for Model A, 0.847 for Model B, and 0.857 for Model C. Model B significantly outperformed Model A (P = 0.0020), whereas no significant difference was observed between Models B and C (P = 0.0816). PNI remained an independent predictor after adjustment for conventional inflammatory markers. Conclusion: A laboratory-based prediction model incorporating PNI demonstrated discrimination comparable to that of a combined clinical-laboratory model while relying exclusively on routinely available objective laboratory parameters. These findings support laboratory-based risk stratification as a practical adjunct to clinical assessment for the early identification of complicated appendicitis.

Introduction Deafness is the most common human sensory deficit. Cochlear implantation is the primary intervention for severe-to-profound deafness. Currently, over 7000 people have bilateral cochlear implants (CIs) in the United Kingdom (UK), most of whom are children. Patient feedback suggests that for children with bilateral CIs, everyday communication is challenging and tiring, with extra effort required to integrate information from two ears, especially in noise, and that current rehabilitation techniques are not engaging, or appropriate to their lifestyles. To address these issues, researchers developed the Both EARS (BEARS) training package comprised of three virtual reality games to improve sound localization and listening in noise. Objectives This protocol describes the design and methodology of a multi-center phase III randomized controlled trial (RCT) to evaluate whether use of the BEARS training package alongside usual care compared to only receiving usual care improves speech-in-noise perception, hearing experiences, vocabulary and quality of life and reduces listening effort in children and young people (aged 8 -16 years (inclusive) with bilateral CIs. Methods This RCT is currently underway in 16 clinical CI departments in National Health Service or university hospitals across the UK. The intervention involves 3 months of spatial-listening training delivered via the BEARS training package in addition to any routine rehabilitation. The control is usual care (routine rehabilitation clinical care pathway). The primary outcome is the difference between the intervention groups in speech-in-noise perception score at 3 months derived from the spatial speech in noise (SSiN-VA) test. Recruitment closes at the end of the day on 31st July 2026, and end of data collection is 31st October 2026. Data analyses will be reported by 31st March 2026. Significance This is the largest known trial of children and young people with bilateral CIs. It will generate high-quality evidence on speech-in-noise outcomes and inform training interventions to improve spatial listening. Trial registration ClinicalTrials.gov registration: NCT05808543; UKs clinical study registry (ISRCTN92454702)

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.

Structural musculoskeletal pain, defined as pain associated with musculoskeletal conditions of the spine and peripheral joints, afflicts persons widely, independent of demographic, and continues to contribute substantially to disability on a global scale. Osteopathic manipulative treatment (OMT) is a non-invasive therapy performed by osteopathic physicians, encompassing a wide variety of techniques meant to heal the dysfunctions manifesting structural musculoskeletal pain. However, the efficacy of OMT in relieving pain symptomatology remains subject to debate. This meta-analysis examines the effect OMT serves to manage structural musculoskeletal pain, measured on a Visual Analog Scale. Three randomized control studies (RCTs) were included, with a total of 231 participants, 117 of which received OMT as part of pain management treatment, the other 114 receiving other treatment modalities. Using the random effects model, the mean difference between OMT and non-OMT treated groups was -1.80 (-7.31; 3.78). Although this mean difference favors OMT with regard to greater reduction in pain, the finding is not statistically significant. Heterogeneity was found to be extraordinarily high (I2 = 96%) and statistically significant (p = <0.0001), albeit attributed to one of the papers, deemed an outlier. With its removal, heterogeneity was still moderate (I2 = 54.4%). Given these findings, the efficacy of OMT in reducing structural musculoskeletal pain cannot be proven. A significant limitation of this study was a low sample size, consisting of 3 RCTs, reducing statistical power. In addition, there was high heterogeneity between studies. More high-quality RCTs with larger sample sizes, standardized methods, and an examination of a broader set of structural musculoskeletal conditions are necessitated to better evaluate the contribution of OMT in pain reduction. Key Words: Pain Management, Osteopathic Manipulative Medicine, Osteopathic Manipulative Treatment, Structural Pain, Orthopaedics, Knee Arthritis, Shoulder Pain, Cervical Spondylosis