Journal of Clinical Medicine

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.

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.

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.

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)

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

Background Cervical spondylotic myelopathy (CSM) is the most common cause of nontraumatic spinal cord dysfunction in adults. For mild disease, guidelines recommend shared decision-making between surgery and structured rehabilitation on the basis of clinical equipoise, yet no comparative effectiveness study has reported outcomes in this population. Whether a randomized trial is feasible is unknown. Methods We conducted two cross-sectional surveys between December 2025 and July 2026: one of patients with surgeon-confirmed CSM recruited from academic outpatient spine clinics, and one of practicing neurosurgical and orthopedic spine surgeons. Respondents rated willingness to participate in (1) a randomized trial of early surgery versus observation and (2) a prospective observational study in which treatment was patient-selected. Responses of likely or very likely were classified as willing. Groups were compared using Fisher exact tests, designs within respondents using exact McNemar tests, and predictors using univariable logistic regression. Results Fifty-four patients and 52 surgeons completed the surveys. Patients were markedly less willing than surgeons to accept randomization (15 of 54, 27.8% versus 44 of 52, 84.6%; p < 0.001). Both groups accepted the observational design (39 of 54, 72.2% versus 51 of 52, 98.1%; p < 0.001), and 26 of 39 patients unwilling to be randomized were willing to enroll in an observational study (p < 0.001). Willingness to be randomized did not differ across mJOA severity (mild 30.4%, moderate 25.0%, severe 27.3%; p = 0.93). Among patients declining randomization, 85.2% cited a wish to retain control over treatment, whereas fear of surgery was cited by one respondent. Forty-five surgeons (86.5%) considered both surgery and observation reasonable, and preference was divided (46.2% favoring early surgery, 48.1% favoring initial observation). Conclusions Surgeons report equipoise and high willingness to randomize, but most patients would decline random allocation, citing a wish to retain treatment choice rather than fear or distrust. A prospective observational study appears the more feasible route to comparative evidence in mild CSM. Feasibility assessments restricted to clinicians may substantially overestimate attainable accrual.

The availability of hearing aids that can connect wirelessly to smartphone technologies via Bluetooth has grown exponentially in recent years. However, there is limited evidence assessing the benefits of user-adjustability afforded by these devices. This study aimed to assess the benefits of smartphone-connected hearing aids and an accompanying application (or app) in new and existing hearing aid users. In this single-centre, prospective, observational study, 44 adult hearing aid users (14 new and 30 existing) were recruited. Participants were fitted bilaterally with smartphone-connected hearing aids that could be adjusted by the user via an app. Self-reported outcome measures were collected at fitting and after seven-weeks of using the device in everyday life. For both new and existing hearing aid users, significant improvements in social participation, hearing-related fatigue, and hearing aid benefit and satisfaction were found. For existing hearing aid users, all outcomes were significantly better for the smartphone-connected hearing aids plus app in comparison to their existing hearing aids that did not connect to a smartphone, all with moderate-to-large clinical effect sizes (d> .6). User-controllability via the app was identified as the key benefit, and most participants (68%) reported that the app met their needs 'extremely' or 'very well'. These results suggest that, when used in conjunction with an app, smartphone-connected hearing aids can improve hearing outcomes due to greater user-controllability to improve listening. Thus, smartphone-connected hearing aids have the potential to facilitate patient-centred care, empowering the individual to successfully manage their hearing loss.

Background: Sex-related disparities in acute coronary syndrome (ACS) recognition and management remain a global health concern. We examined sex-based differences in clinical presentation, management, and outcomes among patients with chest pain attended by emergency medical services (EMS) across Brazil. Methods: We conducted a retrospective study using a registry from 14 Brazilian states between January 2020 and June 2024 within a private hospital network. Patients with chest pain were classified by cardiologists as unstable angina (UA), ST-elevation myocardial infarction (STEMI), or non-ST-elevation myocardial infarction (NSTEMI). Multivariable regression evaluated sex differences in diagnosis, treatment, and outcomes. Sensitivity analyses included state-clustered standard errors and E-values for unmeasured confounding. Results: Among 7,171 patients with confirmed ACS (68.2% male), median age was 63.0 years [IQR 20.0]; women were older than men (67.0 [20.0] vs 61.0 [19.0] years). Diagnoses were UA in 46.7%, STEMI in 18.8%, and NSTEMI in 34.6%. Overall, 91.7% received aspirin and 89.6% at least one additional antiplatelet agent. After adjustment, women had higher odds of chest pain classified as probably or possibly ischemic versus definitely ischemic (adjusted OR 1.51 [95% CI 1.33-1.72] and 1.60 [1.37-1.86], respectively) and lower odds of STEMI and NSTEMI relative to UA (adjusted OR 0.59 [0.51-0.68] and 0.74 [0.66-0.83], respectively). Door-to-ECG time was longer in women unadjusted ({beta}=1.53 minutes [0.24-2.82]) but not after adjustment ({beta}=1.04 [-0.27 to 2.36]). In-hospital mortality did not differ between sexes, with no evidence of excess short-term mortality in women. Conclusions: Within a private hospital network in Brazil, women with confirmed ACS were more often classified with less definitely ischemic chest pain and less frequently with STEMI or NSTEMI than men. Door-to-ECG differences did not persist after adjustment, and mortality did not differ by sex. These findings support sex-sensitive triage and diagnostic protocols to reduce inequities in ACS recognition and treatment.

Background. In Europe, first-trimester combined screening with the Fetal Medicine Foundation (FMF) algorithm identifies women at increased risk of preeclampsia who may benefit from personalized aspirin prophylaxis. However, a substantial proportion of early-onset preeclampsia (EOPE) remains undetected at clinically acceptable specificity. Objective. To evaluate the first-trimester performance of MaiRa for early-onset preeclampsia (EOPE) risk stratification by benchmarking it against FMF screening in the same women, characterizing discordant patient-level classification profiles and exploring potential implementation strategies. Study Design. This secondary case-control analysis was nested within the prospective, multicentre PREMOM cohort [NCT04990141], which enrolled women with singleton pregnancies across 14 tertiary hospitals in Spain. First-trimester MaiRa and FMF risk estimates were evaluated in the same 126 pregnant women, comprising 99 uncomplicated controls and 27 EOPE cases, defined by disease onset before 34 weeks. Discrimination was compared using a stratified paired bootstrap analysis of the areas under the receiver-operating-characteristic curves. Performance was assessed at prespecified clinical thresholds, and detection rates were evaluated at fixed false-positive rates. Universal and contingent MaiRa implementation strategies were also evaluated. Results. MaiRa showed greater first-trimester discrimination for EOPE than FMF combined screening (AUC, 0.974 vs 0.900; P=.040) and consistently achieved higher detection rates across fixed false-positive rates. At false-positive rates of 5% and 10%, MaiRa detected 85.2% and 92.6% of EOPE cases, compared with 44.4% and 70.4% for FMF, respectively. Patient-level analysis demonstrated that MaiRa identified 12 of 27 EOPE cases (44.4%) classified as low risk by FMF; these pregnancies generally exhibited less abnormal conventional first-trimester profiles, including fewer maternal risk factors, lower mean arterial pressure and lower uterine artery pulsatility index, yet 8 of 12 (66.7%) subsequently developed severe EOPE. Exploratory implementation analyses showed that universal MaiRa screening achieved the highest EOPE detection, whereas a contingent strategy using FMF for triage and reflex MaiRa testing reduced molecular testing to 35.7% of pregnancies while maintaining 77.8% sensitivity and 97.0% specificity. Conclusion. MaiRa provided greater first-trimester discrimination for EOPE than conventional combined screening and detected additional pregnancies that later developed severe disease despite less abnormal conventional screening profiles. The findings suggest that maternal plasma cfRNA profiling captures biological alterations not fully reflected by combined first-trimester screening and support further prospective evaluation in an independent, unselected obstetric population. Key words: early-onset preeclampsia; first-trimester screening; cell-free RNA; liquid biopsy; Fetal Medicine Foundation algorithm; combined screening; risk stratification; aspirin prophylaxis.

Background Cardiac magnetic resonance imaging (CMR) T1 and T2 mapping accurately detect acute heart transplant rejection, but the diagnostic value of CMR-derived strain imaging remains uncertain, particularly for right ventricular strain. Data incorporating donor-derived cell-free DNA (dd-cfDNA) into a composite reference standard are limited. We evaluated the diagnostic accuracy of CMR-derived left and right ventricular strain and ejection fraction for detecting acute rejection in pediatric and adult heart transplant recipients. Methods Blinded analysis of 1.5T CMR studies was performed in pediatric and adult heart transplant recipients 1-24 months post-transplant, as well as during five additional episodes of acute rejection occurring 3-14 years post-transplant. Left and right ventricular strain and ejection fraction were quantified using semi-automated post-processing. Acute rejection was defined using a composite reference standard comprising endomyocardial biopsy (EMB), clinical assessment, and dd-cfDNA. Diagnostic performance was assessed using cut-off values derived from receiver operator characteristic (ROC) analysis. Results Among 214 CMR studies in 58 patients, 13 cases of acute rejection were identified. Diagnostic performance for detecting acute rejection was moderate for pediatric right ventricular longitudinal strain (AUC 0.782, 95% CI 0.565-0.999), whereas all other cardiac functional parameters demonstrated limited discrimination in both pediatric and adult patients (AUC 0.536-0.739). Models based on individual rejection indicators (EMB, clinical assessment, and dd-cfDNA) also showed poor diagnostic accuracy. Conclusion CMR-derived left and right ventricular strain and ejection fraction demonstrated limited ability to independently detect acute rejection. However, strain abnormalities, particularly RVLS in pediatric patients, may reflect downstream functional effects in more advanced rejection and may complement T1 and T2 mapping in assessing rejection severity.

Background. Guidelines recommend surgery for moderate and severe cervical spondylotic myelopathy (CSM) but support either surgery or nonoperative care for mild disease. How patients weigh the adverse events associated with each pathway is not well characterized. Methods. We conducted a three-arm randomized vignette experiment among United States adults aged 40 years and older recruited through an online research panel. All participants read an identical description of mild CSM and were randomized to one of three scenarios: surgery that improved symptoms, surgery that halted progression without improvement, or nonoperative management with symptom progression. Participants in the surgical scenarios rated 12 possible complications and those in the nonoperative scenario rated 8 progression outcomes. For each item, participants rated how strongly it would influence their decision (0-10) and whether they would still choose the same treatment. Items for which participants would no longer choose the same treatment were termed dominant decision factors. Results. Of 276 respondents, 263 (95.2%) were analyzed. Dominant factor rates ranged from 13.5% to 87.8% across complications. Complications described as persisting at one year produced substantially higher rates than the same complications described as resolving by three months. Adverse events more frequently constituted dominant factors when surgery was framed as offering less benefit, although differences between scenarios were not statistically significant. In the nonoperative scenario, worsening bladder control (56.6%) and neck pain interfering with sleep (53.0%) were the strongest influences, exceeding needing a cane to walk (32.1%). Conclusions. Treatment decisions for mild CSM are driven primarily by the expected permanence of adverse events and their anticipated impact on daily quality of life, rather than by conventional neurological metrics or surgical benefit framing.

Rationale: Dislocation is the leading reason for early revision surgery. To address the problem of dislocation, the dual-mobility (DM) cup was developed in France in the 1970s. This cup should provide more stability and biomechanically reduce the risk of dislocation. In the Netherlands, most DM cups are placed in specific patients, e.g. with cognitive impairment and for revisions due to recurrent dislocations. Despite the increased and, in some countries, broad use of DM cups, high quality evidence of their (cost)effectiveness is lacking. This study aims to perform a trial to fill this gap in knowledge. Much of the information needed to judge the effectiveness of DM cups is already incorporated in the Dutch Arthroplasty Register (LROI). This register lends itself perfectly for a nested RCT towards this aim. Objective: The primary objective is to investigate whether there is a difference in the number of hip dislocations following primary total hip arthroplasty (THA), using the posterolateral approach, with a DM cup compared to a unipolar cup in elderly patients 1 year after surgery. The secondary objectives are: to investigate whether there is a difference in the number of revisions; to investigate what the cost-effectiveness and cost-utility is of a DM cup compared to a unipolar cup at 1 year follow-up; to investigate whether there is a difference in the number of hip dislocations and revisions between a DM cup and a unipolar cup 2 years after surgery; to investigate whether there is a difference in patient reported outcomes between a DM cup compared to a unipolar cup 1 and 2 years after surgery; to compare the number of hip dislocations, revisions and PROM data between patients in the randomized DM group and patients in an observational cohort DM group. Finally, long-term survival of DM and unipolar cups will be evaluated based on revision and mortality data registered in the LROI. Study design: Prospective multi-center international wide within the European Union (EU), single blinded RCT, nested in the national registry. Study population: Patients [&ge;] 70 years old, undergoing an elective primary THA. Intervention (if applicable): The intervention group receives a THA with a dual mobility cup, the control group receives a THA with a unipolar cup. Main study parameters/endpoints: Primary: The number of dislocations. Secondary: costs, patient reported outcomes and implant survival.

Background: Lumbar disc herniation, with or without concomitant disc degeneration, is a major cause of lumbar radiculopathy and low back pain, which also a key public musculoskeletal disorder without an exact pathophysiology. Studies have suggested that inflammatory cells and biochemical markers of inflammation also play an important role in lumbar radiculopathy in addition to nerve compression. The aim of the present study was to assess the association of selected circulatory inflammatory markers (CRP, hs-CRP and E-selectin) in patients with lumbar disc herniation without radiological degeneration (LDH) and lumbar disc herniation with radiological degeneration (LDHD). Materials & methods: This case-control study included 208 participants, comprising 104 patients with lumbar disc pathology and 104 controls. Patients were further stratified into LDH (n=67) and LDHD (n=37). Serum CRP, hs-CRP and E-selectin concentrations were measured. Results: Among the patients, 35.6 % presented with LDHD while 64.4 % had only LDH. Significantly increased median hs-CRP (p<0.001) and CRP (p<0.001) were observed in patients groups compared to controls, while CRP showing a consistent independent association across the combined disease (OR=1.68, 95% CI=1.33-2.14, p<0.001), LDHD (OR=1.62, 95% CI=1.16-2.20, p=0.005) and LDH (OR=1.69, 95% CI=1.30-2.20, p<0.001) multivariable models. No significant difference was observed in serum E-selectin between the study groups. Multivariable models incorporating inflammatory and clinical variables demonstrated substantially greater discriminatory performance than individual biomarkers alone. Conclusion: Elevated circulating CRP and hs-CRP concentrations were associated with lumbar disc pathology, with CRP showing a consistent independent association across the combined disease, LDH and LDHD multivariable models, whereas E-selectin showed no significant association. Multivariable models incorporating inflammatory and clinical variables demonstrated greater discriminatory performance than individual biomarkers. These findings support a potential systemic inflammatory component in lumbar disc pathology, although the cross-sectional nature of the measurements does not establish causality or a local inflammatory response within the disc.

Background: The placenta has a unique transcriptomic profile, including microRNAs that are secreted into maternal circulation throughout pregnancy. MicroRNAs are small, non-coding RNA that post-transcriptionally regulate gene expression. Spontaneous preterm birth (sPTB) is associated with substantial differences in both placental pathophysiology and placental gene expression compared to term birth. We aimed to generate microRNA signatures of sPTB and map them to target genes using a microRNA-mRNA network. Methods: This study was conducted within the Conditions Affecting Neurocognitive Development and Learning in Early childhood (CANDLE) study. Placental samples were collected at delivery, and RNA was isolated for mRNA and microRNA sequencing. To investigate sPTB, this study excluded placental samples of participants with iatrogenic indications for PTB or induced labor. We examined differences in microRNA expression in participants who delivered before 37 weeks (N=35) compared to term participants (N=404) in a series of covariate-adjusted linear regression models. We used paired placental microRNA and mRNA expression data from this cohort to validate associations between computationally predicted microRNA-mRNA pairs and establish a microRNA-mRNA network. Results: Expression of 7 microRNAs were increased in sPTB (FDR<0.05) and were inversely correlated with sPTB-associated genes involved in immune signaling. Expression of 12 microRNAs were decreased in sPTB, including 4 members of the maternally expressed chromosome 14 microRNA cluster (miR-376a-3p, miR-376c-3p, miR-377-3p, and miR-381-3p). These microRNAs were predicted to negatively regulate oxidative phosphorylation genes that were increased in sPTB. The associations between miR-376c-3p and miR-377-3p and oxidative phosphorylation were confirmed in microRNA knockdown experiments. Conclusions: This study highlights potential biological mechanisms by which placental microRNA dysfunction might contribute to sPTB and highlights putative sPTB biomarkers that may be detectable in maternal circulation.

Introduction We are currently working on the BEARS (Both Ears) virtual reality (VR) Randomised Controlled Trial. We are recruiting 272 deaf children and young people who use bilateral (both ears) cochlear implants (CI) to examine if using the BEARS VR games helps their hearing in background noise and ultimately their quality of life. Clinical trial participants should be representative of the population with the health condition, although this is rarely achieved in practice as people from ethnic minorities or those from more deprived areas may face barriers to participation. Study Design Mixed methods design Objectives Use a literature review and collection of data from cochlear implant centres to establish the sociodemographic characteristics of deaf children aged 8 to 16 years with bilateral cochlear implants in the United Kingdom (UK). a. Establish the sociodemographic characteristics of the families recruited to the BEARS clinical trial in the first six months, and compare with the age-matched population of deaf children with bilateral cochlear implants in the UK. b. Analyse the BEARS clinical trial pre-screening diversity data. c. Implement an established recruitment intervention method in a workshop to explore and optimise recruitment number and diversity. d. Compare the final six months of recruitment data diversity with the initial six months. Use interviews and focus groups to collect qualitative data from children and their families who chose not to take part in BEARS, clinicians, and family representatives (e.g. teachers) to explore barriers and facilitators to families taking part in BEARS. Amend the BEARS scale-up plan based on new learning. Methods Literature and scoping reviews, quantitative analysis of BEARS recruitment data, in-depth interviews, paired interviews, focus groups Sample size Qualitative sample: 10-15 children aged 8-16 with bilateral CI, 10-15 parents/carers of children with bilateral CI, 10-12 clinicians and 10-12 family representatives. Significance This work will evaluate how diverse the BEARS clinical trial recruitment is and whether it is representative of the UK population of children with bilateral cochlear implants. We will investigate recruitment barriers and implement measures to try to improve recruitment diversity.

Gaps remain in the evidence base for postoperative management following forefoot surgery. A recent randomized controlled trial (ClinicalTrials.gov NCT04927234) demonstrated improved outcomes with intermittent one Hertz (Hz) neuromuscular electrical stimulation (NMES) of the common peroneal nerve. This sub-analysis evaluates its effect in patients undergoing forefoot surgery. Forty-two patients undergoing forefoot procedures were included; 26 received NMES plus standard of care (SOC) and 16 received SOC alone. Wound healing was assessed at 14 days. Edema was measured using the figure-of-eight (FO8) method. Patient-reported outcomes were assessed using the Manchester-Oxford Foot Questionnaire (MOXFQ). At 14 days, complete wound healing occurred in 77% of patients receiving NMES plus SOC compared with 40% in the SOC group (p<0.05). Edema reduction was significantly greater in the NMES group, with a 74% relative reduction compared with SOC (p=0.02). Intermittent one Hz NMES of the common peroneal nerve was associated with improved wound healing and reduced postoperative edema following forefoot surgery.

Background Optimal timing for resuming direct oral anticoagulants (DOACs) after high-risk endoscopic procedures remains uncertain, and existing recommendations derive largely from expert opinion. The objective of this study was to characterize practice patterns and perceptions among endoscopists and outcome prioritization among patients with atrial fibrillation, in order to inform the design of the planned RESUME randomized trial. Methods We conducted parallel, cross-sectional surveys of practicing endoscopists and patients with atrial fibrillation using electronic questionnaires administered via Qualtrics. The endoscopist survey, distributed through the American Society for Gastrointestinal Endoscopy, assessed practice patterns, acceptability of early (postoperative day [POD] +1), intermediate (POD +3), and late (POD +5) resumption strategies, and perceptions of clinical equipoise. The patient survey, distributed through two advocacy organizations, assessed perceived confidence in existing guidance and prioritization of bleeding versus thromboembolic risk. Results A total of 201 endoscopists and 477 patients (92.5% taking a DOAC) provided evaluable responses. Endoscopists demonstrated wide variability in preferred timing of DOAC resumption after a standardized high-risk mucosal resection vignette, ranging from same-day resumption to delays beyond five days. POD +2 was the most commonly selected strategy, and most respondents rated more than one proposed RESUME trial arm as acceptable. Nearly all endoscopists (98.9%) rated a randomized trial to determine optimal timing as important. Patient preferences regarding bleeding versus stroke risk were heterogeneous and symmetrically distributed around the neutral response on a five-point ordinal scale. Preferences did not differ by prior stroke or transient ischemic attack, prior major bleeding, age, sex, or geographic region. More than half of patients (54.6%) reported being very or somewhat confident that clear guidance exists regarding DOAC resumption, despite the absence of high-quality randomized evidence informing this question. Conclusions Endoscopists demonstrate substantial practice variability and clinical equipoise, and patients demonstrate heterogeneous and balanced outcome preferences, regarding the timing of DOAC resumption after high-risk endoscopy. These findings support the ethical justification and relevance of the planned RESUME trial.