Postoperative gastrointestinal (GI) bleeding is a serious complication after hip fracture surgery in older adults, yet perioperative risk stratification remains limited because commonly used GI-bleeding scores are not tailored to orthopedic settings. This study aimed to develop and internally validate an interpretable model to predict postoperative GI bleeding risk in elderly hip fracture patients, using data routinely available during the perioperative period. We retrospectively included 342 elderly patients who underwent hip fracture surgery at the Third Hospital of Hebei Medical University from January to December 2023. The outcome was GI bleeding within 1 month after surgery, confirmed by medical records and/or telephone follow-up. Patients were randomly split into a training set (n = 242) and a validation set (n = 100). Predictors were screened using LASSO with 10-fold cross-validation, followed by multivariable logistic regression to identify independent risk factors. Ten prediction algorithms were trained and compared. Model performance was assessed by AUC, calibration, and decision curve analysis, and interpretability was evaluated using SHAP. GI bleeding occurred in 38 patients (11.1%). Multivariable analysis identified four independent predictors: alcohol consumption history (OR 8.109, 95% CI 2.463-26.69), glucocorticoid use (OR 4.922, 95% CI 1.055-22.97), NSAID use (OR 6.851, 95% CI 1.811-25.915), and higher systemic immune-inflammation index (SII) (OR 1.001, 95% CI 1.000-1.002). Among the tested models, LightGBM showed the best overall performance, with AUCs of 0.843 (training) and 0.817 (validation), good calibration, and the highest net benefit on decision curve analysis. SHAP results ranked feature importance as SII, NSAID use, alcohol consumption history, and glucocorticoid use, consistent with regression findings. We developed and validated an interpretable LightGBM model that predicts postoperative GI bleeding risk in elderly hip fracture patients using routinely available clinical data. The final model incorporates only preoperative variables, systemic inflammation, NSAID use, alcohol history, and glucocorticoid use, supporting its application for early risk stratification prior to surgery.
To compare perioperative outcomes between the 48-h short-stay pathway and traditional inpatient management for patients undergoing robot-assisted partial nephrectomy (RAPN), and to evaluate the feasibility, safety, recovery efficiency, and economic benefits of the 48-h short-stay pathway. This retrospective study included 175 patients who underwent RAPN between February 2022 and June 2024. Patients were assigned to a 48-h short-stay group (n = 60) or a traditional inpatient group (n = 115). A 1:1 propensity score matching (PSM) was conducted to balance baseline characteristics, including age, sex, BMI, comorbidities, tumor features, surgeon identity, and surgical year. Perioperative outcomes, recovery indicators, complications, and medical costs were compared. After PSM, 53 matched pairs were analyzed. The short-stay group showed significantly shorter operative time, less intraoperative blood loss, shorter warm ischemia time, earlier mobilization, earlier oral intake, faster bowel function recovery, and shorter bed rest (all P < 0.05). The short-stay group had 71.7% of patients discharged on postoperative day (POD) 1 and 100% within 48 h, while the traditional group had 22.6% on POD1, 33.96% on POD2, and 43.4% on POD ≥ 3 (P < 0.001). Both total and postoperative hospital stays were significantly shorter in the short-stay group (2.00 vs. 6.00 days, P < 0.001), with lower hospitalization costs (P < 0.001). Postoperative creatinine was lower in the short-stay group (P = 0.023), while creatinine change was comparable (P = 0.063). Complication rates, emergency department visits, and 30-day readmission rates were similar between groups (all P > 0.05). The short-stay group had a significantly lower drain placement rate (P = 0.002) without increased adverse events. The 48-h short-stay pathway for selected patients undergoing RAPN is feasible and safe. It accelerates postoperative recovery, shortens hospital stay, reduces medical costs, and optimizes healthcare resource utilization, without compromising safety or oncological early outcomes.
Breast cancer patients often experience significant psychological distress. This study examined distress trajectories from diagnosis to 6 months post-treatment and explored differences across demographic, medical, and psychosocial subgroups. In this prospective cohort study, 528 patients with breast cancer were recruited between 1 December 2023 and 31 December 2024. Assessments were conducted at baseline (at diagnosis, T0), after the first treatment (T1), mid-treatment (T2), at treatment completion (T3), and at three (T4) and six months (T5) post-treatment. Growth mixture modeling (GMM) was used to identify distinct trajectories of psychological distress. Multinomial logistic regression analysis was performed to examine associations between patient-related factors and trajectory membership. Three psychological distress trajectories were identified: a high-distress remission group (17.05%), a moderate-stable distress group (11.93%), and a low-fluctuating distress group (71.02%). Multivariable analyses showed that higher educational attainment, breast-conserving surgery, early disease stage, partial self-management ability, and strong social support were associated with membership in the moderate-stable or low-fluctuating groups (p < 0.05). Employment, health insurance coverage, avoidant medical coping style, and higher baseline anxiety and depression scores were concurrently associated with membership in the high-distress remission group (p < 0.05). Although psychological distress generally decreased over time, 71.02% of patients followed a low-fluctuating trajectory, 11.93% maintained moderate distress with potential risk of persistence, and 17.05% showed high initial distress that remitted substantially within 6 months. Continuous monitoring and early psychosocial support are recommended, particularly for patients with moderate- or high-risk trajectories.
Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors composed of cells exhibiting an epithelioid morphology. These cells typically arrange around small blood vessels (perivascular spaces) and display dual differentiation characteristics of smooth muscle cells and melanocytes. Diagnosis is challenging due to the absence of specific symptoms or tumor markers. This case features a young male patient with a large hepatic PEComa, whose imaging findings resemble those of hepatocellular carcinoma. We have detailed the entire process from diagnosis to treatment to aid in differential diagnosis and surgical planning. A 31-year-old male patient with no prior medical history underwent a routine health examination 20 days prior to presentation. Although the patient was asymptomatic, ultrasound revealed an incidental hepatic lesion measuring 58 × 50 × 45 mm (maximum diameter 58 mm, or 5.8 cm). The screening center suspected a hemangioma. Subsequently, he presented to our hospital. Comprehensive imaging studies, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), revealed a 58 mm-diameter space-occupying lesion in segments V and VIII of the right hepatic lobe. Imaging findings initially raised suspicion for hepatocellular carcinoma. To minimize surgical trauma and preserve liver function, our team discussed surgical approaches and ultimately decided on a laparoscopic partial hepatectomy. During the procedure, we obtained a specimen for pathological examination. The final histopathological analysis confirmed the diagnosis of a PEComa with undetermined malignant potential. The patient recovered smoothly postoperatively and was successfully discharged. PEComa has an insidious onset and is rare. Early diagnosis is often challenging, and imaging studies typically show no highly specific findings. Clinical diagnosis frequently relies on biopsy. In terms of treatment, radical resection (R0 resection, i.e., negative margins) represents the definitive therapeutic approach.
Hidradenitis suppurativa (HS), an inflammatory skin disorder characterized by painful nodules and abscesses, has varying prevalence among different races/ethnicities. This study explored the social drivers of health, burden, and impact of HS among different racial and ethnic groups. An online, cross-sectional survey was conducted among adult patients with HS (September 2023-December 2023) in the USA. Patients were recruited through HS Connect (patient advocacy group) and AmeriSpeak (US national sample panel). Descriptive data were collected using patient-reported outcome measures and de novo questions about patients' disease knowledge and perception, healthcare access and utilization, impact on quality of life (QoL), and social impact. All analyses were descriptive and stratified by racial/ethnic groups. The study included 583 patients (mean age, 34.8 years; 95.5% female) representing a range of racial backgrounds: Black or African American (n = 273; 46.8%), white (n = 236; 40.5%), Two or More Races (n = 47; 8.1%), American Indian or Alaska Native (n = 18; 3.1%), Asian (n = 7; 1.2%), and Native Hawaiian and Other Pacific Islander (n = 2; 0.3%). Ethnic representation also varied (Hispanic/Latino = n = 76; 13.0%). Patients of all races and ethnicities reported considerable QoL impact (Dermatology Life Quality Index, EQ-5D-5L), with results for smaller subgroups (n < 10) included for descriptive completeness only and not intended for comparison with other groups. During flaring, most patients used over-the-counter products/medications (54.2%) or nonmedical intervention/home remedy (56.9%) Up to 36.5% of patients reported challenges in procuring food, utilities, medicine/healthcare, phone, clothing, or childcare when needed in the past year. Among those who paid out-of-pocket for their HS treatment, 55.6% reported that it stopped them from visiting a healthcare provider for treatment. The findings indicate a high burden and impact of HS across all races and ethnicities. Patients reported social drivers of health and challenges with healthcare utilization, indicating the need for integrating social workers and care management teams in dermatology practice, which could facilitate improved care of patients with HS. Hidradenitis suppurativa is a painful skin condition that causes lumps and abscesses. It affects people of all races and ethnicities but is more common in Black or African American individuals. This study surveyed 583 adults in the USA to understand how hidradenitis suppurativa affects people from different racial and ethnic backgrounds. Our focus was on how the disease impacts their daily lives, their ability to access healthcare, how often they visit doctors, their quality of life, and their mental and emotional well-being. Most people said that hidradenitis suppurativa lowers their quality of life and makes daily activities harder. During flaring, many used home remedies instead of seeing a doctor. People suffering from hidradenitis suppurativa also reported trouble getting basic needs such as food, medicine, and transportation. These challenges occurred among patients from different racial and ethnic groups; results for very small subgroups (Asian, Native Hawaiian/Other Pacific Islander) are reported descriptively only and should not be interpreted as representative of these groups or compared with other groups. The research underscores the importance of improving awareness and tailoring care for people with hidradenitis suppurativa, particularly those facing barriers to healthcare.
Work in eating disorder (ED) services presents unique challenges and rewards that may affect clinicians' work-related and personal wellbeing. However, research on ED clinician needs, views, and experiences is still sparse, despite major service changes since the COVID pandemic. This study aims to explore and conceptualise NHS ED clinicians' work-related experiences, challenges, and needs, in order to inform future clinicians wellbeing and service improvement strategies. Clinicians working in ED services (N = 19) were interviewed using a semi-structured interview guide that probed their professional experiences, work-related needs, and views. Interviews were analysed using NVivo, following guidance from Braun and Clarke (2006) for reflexive thematic analysis. A holistic ecological systems framework for ED services was created, comprised of five levels of influence: intrinsic, intra-personal, departmental, systemic, and societal. These levels contain nine themes: [1] clinician motivation for working in ED services [2], complexities of ED management [3], clinician personality and emotional disposition [4], team dynamics [5], supervision, management, and organizational support [6], service-level concerns [7], macro-level systemic concerns [8], broader societal challenges in ED care, and [9] COVID-related challenges. Key concerns included the chronic nature and risk of EDs, growing service demands amid limited resources, and regulation through guidelines and commissioning targets. This presented framework illustrates the multifaceted array of complexities faced by ED clinicians. The interplay of personal, inter-personal, and systemic factors is explored, with clinicians' interest in and commitment to ED care at the core of the framework. These areas can be targeted to improve clinician job satisfaction and reduce burnout risk, with the goal to provide optimal patient care. This study explores the experiences and wellbeing of clinicians working in NHS eating disorder (ED) services. Through interviews with clinicians, the research explored both the positive and difficult parts of their job. While staff felt strongly committed to helping people with EDs, many also described feeling emotionally drained and frustrated. This was often due to high workloads, not enough resources, and long waiting lists. Clinicians found it especially hard when they had to follow strict service rules that didn’t work well for individual patients, and when they had to manage complex medical risks. Supportive teams and good supervision helped some staff cope. Wider problems like staff shortages, poor communication between services, and lack of funding compounded emotional strain. The findings show that ED clinicians urgently need more support, including better resources, more flexible ways of working, and proper training, to give safe, effective care without burning out.
The Clinical Genome Resource (ClinGen) Von Hippel-Lindau (VHL) Variant Curation Expert Panel (VCEP) has created variant classification specifications tailored to the VHL gene, including phenotype-driven and evidence-based criteria, utilizing somatic and germline mutational hotspots, along with functional and in-silico data. Using the American College of Medical Genetics and Genomics (ACMG) guidance and the ClinGen Sequence Variant Interpretation (SVI) recommendations, the VCEP made substantial modifications to 8 evidence codes (PVS1, PS3, PS4, PM1, BS2, BS3, BS4, BP5), while 14 had minor changes, and 6 were not used (PM3, PP2, BP1, PP4, PP5/BP6). The VHL VCEP applied two literature sets of over >428 papers in Clinical Interpretations of Variants in Cancer (CIViC) and >8700 structured annotations using Hypothesis. From 31 pilot variants, 15 remained pathogenic/likely pathogenic, 9 resolved to benign through the stand-alone benign evidence code while 7 variants with initial uncertain classifications lacking additional evidence, remained uncertain. The versioned VHL VCEP specifications are publicly available in the ClinGen Criteria Specifications Registry and will enhance the transparency and consistency of variant classifications for this highly sequenced hereditary cancer gene.
Tanzania has adopted artificial intelligence (AI)-assisted chest X-ray screening for tuberculosis (TB), including the use of CAD4TB version 6, which is registered by the Tanzania Medicines and Medical Devices Authority (TMDA). While GeneXpert, practical reference standard used in routine practice, remains the primary bacteriological confirmatory test in routine practice, there is currently no established national threshold for CAD4TB use in either active case finding (ACF) or passive case finding (PCF) settings. This study evaluates the implementation and operational use of CAD4TB version 6 within mobile TB screening units in Tanzania and highlights challenges affecting its effective use. We conducted a retrospective analysis of screening data from 11,923 individuals collected from mobile clinics equipped with digital X-ray, CAD4TB version 6, and GeneXpert systems. Comparisons were made between manual chest X-ray interpretation, CAD4TB scores, and GeneXpert results within the subset of individuals who underwent confirmatory testing. The findings reveal substantial inconsistencies in screening workflows, including non-uniform use of CAD4TB prior to GeneXpert testing, missing radiological records, and deviations from intended protocols across sites. Descriptive analysis showed that CAD4TB scores generally aligned with GeneXpert-positive cases within the tested subset; however, due to selective application of GeneXpert and incomplete data, these observations cannot be interpreted as measures of diagnostic accuracy. This study should be interpreted as an implementation and operational assessment of AI-assisted TB screening rather than a diagnostic accuracy or threshold-setting study. The findings highlight important gaps in protocol adherence, data completeness, and workflow standardization, underscoring the need for prospective, protocol-driven studies to establish validated national thresholds for CAD4TB use in Tanzania.
The progressive skeletal muscle degeneration observed in Duchenne Muscular Dystrophy (DMD) patients requires multiple cycles of satellite cells (SCs) activation to promote tissue regeneration. Dystrophic SCs present intrinsic defects, and the disrupting fibrotic niche hinders appropriate muscle recovery. Traditional 2D culture systems face challenges in modeling the DMD muscle niche and SCs behavior. Our aim was to validate a 3D culture of skeletal muscle spheroids (iSMS) for DMD modeling, as compared to the traditional 2D culture, while investigating the pathophysiological mechanisms of dystrophin deficiency in vitro. To compare iSMS with traditional 2D myogenic differentiation, we differentiated wild-type (WT), dystrophic (DMD) isogenic induced pluripotent stem cells (iPSCs), as well as iPSCs derived from DMD patients, characterized myogenic markers levels and assessed differences in proliferation and differentiation using RT-qPCR, immunofluorescence, and flow cytometry. Our data showed that iSMS improved PAX7 expression in vitro, while MYOD1, MYOG, MYF5, and MYH3 expression were significantly reduced. These findings suggest that, at three weeks of myogenic differentiation, iSMS cultures retained satellite-like cells in a less activated, progenitor-like state. Accordingly, we identified higher expression of canonical Notch signaling genes such as JAG1 and NOTCH1 in iSMS compared to 2D. We also characterized the response of 2D and iSMS to terminal differentiation medium, providing a valuable comparison with muscle fibers derived from human adult myoblasts. Additionally, we showed that DMD iSMS-derived progenitors proliferated at reduced levels compared with WT, a characteristic not observed in progenitors derived from 2D cultures. Finally, we performed iSMS and 2D myogenic differentiation of iPSC lines from three patients with DMD. Our results highlight important advantages of using the iSMS differentiation platform over 2D for DMD in vitro modeling. Exploring these 3D systems may help to gain a deeper understanding of SCs behavior to advance in novel treatments for DMD, which might be applicable to other forms of muscular disorders.
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 13%. Surgical resection followed by adjuvant chemotherapy remains the only curative approach. However, complications such as postoperative pancreatic fistula (POPF) and postpancreatectomy hemorrhage (PPH) often delay or prevent further treatment. Reliable preoperative biomarkers for predicting these complications are lacking. This study investigated soluble CD40 (sCD40) as a potential predictive marker for pancreas-specific complications after pancreatoduodenectomy (PD) in patients with PDAC. Preoperative serum samples from 185 patients with PDAC undergoing pylorus-preserving pancreatoduodenectomy or a Whipple procedure were analyzed using enzyme-linked immunosorbent assay to quantify sCD40 levels. Clinical and postoperative data were systematically collected and classified. Of the 185 patients, 151 underwent pylorus-preserving PD and 34 a Whipple procedure. Clinically relevant POPF occurred in 9.7% and PPH in 7.6% of patients. Preoperative sCD40 levels were significantly lower in patients who developed POPF or PPH (P = 0.025 and P = 0.008). The association remained significant in multivariable analysis. Receiver operating characteristic analysis demonstrated an area under the curve of 0.660 for sCD40. Adding leukocytes and body mass index improved predictive performance (area under the curve 0.705 for POPF and 0.752 for PPH). Reduced preoperative sCD40 serum levels are associated with a higher risk of POPF and PPH after PD. Combining sCD40 with leukocytes and BMI may enhance preoperative risk assessment in patients with PDAC.
With the advent of the immunotherapy era, the combination of radiotherapy and immunotherapy has become a critical strategy to enhance patient outcomes. In addition to its direct cytotoxicity, radiotherapy modulates the immune response within the tumor and its surrounding microenvironment by stimulating the body's anti-tumor immune response. This interplay provides the rationale for combining radiotherapy with immunotherapy. This review will summarize the immunomodulatory mechanisms of radiation therapy, evaluate the clinical efficacy and safety of combining radiotherapy with immunotherapy, and outline its current applications, challenges, and future potential. In the future, the combination of radiotherapy and immunotherapy holds immense potential in esophageal cancer treatment. Through additional prospective clinical trials exploring optimal combinations, timing, and biomarkers, we can further refine treatment strategies and enhance patient survival.
The role of diet in multiple sclerosis (MS) development is still a matter of debate and its impact on MS course is not well understood. We tried to investigate the possible role of adolescent diet in late-onset multiple sclerosis (LOMS) odds. LOMS patients were obtained from the National MS Registry of Iran. Controls were sex and age matched with no history of neurological disorders. We assessed dietary factors using a questionnaire based on multinational studies. Food consumption levels were classified into low, medium, and high for each item. Logistic regression models were used to evaluate diet's impact on LOMS odds. We included 83 LOMS cases and 207 matched healthy controls. The mean age for LOMS patients was 61.14, compared to 61.51 years for controls. The results showed that higher consumption of dairy as in the third tertile associated with 79% decline in LOMS odds (AOR: 0.21; 95%CI: 0.09-0.47). Higher seafood consumption, in the third tertile was associated with a decrease in the odds of LOMS (AOR: 0.32; 95%CI: 0.14-0.72). Furthermore, increased nut consumption, in the third tertile (AOR: 0.37; 95%CI: 0.18-0.77), decreased the odds of LOMS. Additionally, higher consumption of fruits (AOR: 0.22; 95%CI: 0.07-0.63) and vegetables (AOR: 0.26; 95%CI: 0.12-0.55) was linked to a reduced odds of LOMS. This research highlights the advantageous impact of dairy products, seafood, nuts, fruits, and vegetables in lowering the LOMS odds. Hence, advocating for nutrition role in development of LOMS could represent a preventive measure for people susceptible to MS.
Peptic ulcer disease (PUD) remains a significant public health concern globally, particularly in regions with high prevalence of risk factors such as Helicobacter pylori infection and Non-Steroidal Anti-Inflammatory Drug (NSAID) use. This study aimed to investigate the prevalence of PUD and its associated risk factors among hospitalized patients in a tertiary hospital in southwest Iran. A mixed-methods design was employed, including a comprehensive literature review, checklist development and validation via a modified Delphi process, a cross-sectional prevalence study, and a hospital-based case-control study. Data were collected from 43,324 patient records (2019-2023) at Abadan University Teaching Hospital. Risk factors were assessed using a validated 21-item checklist, and multivariate logistic regression was used to identify independent predictors of PUD. Among all admissions, 6,874 cases of PUD were identified, indicating a point prevalence of 15.9% (95% CI: 15.6-16.2). NSAID use (75.3%), H. pylori infection (70.1%), smoking (46.9%), and corticosteroid use (30.2%) were highly prevalent among PUD patients. Significant independent risk factors included age ≥ 60 years (AOR: 1.65), NSAID use (AOR: 2.58), H. pylori positivity (AOR: 2.41), smoking (AOR: 1.45), and ulcer size ≥ 5 mm (AOR: 2.19). Despite the high rate of NSAID use, only 26.4% received gastroprotective therapy. The findings underscore the high burden of PUD in hospitalized patients in southwest Iran, with modifiable risk factors such as NSAID use, H. pylori infection, and smoking playing a critical role. Targeted interventions, including Proton Pump Inhibitor (PPI) co-prescription, H. pylori eradication, and lifestyle modifications, are essential to reduce PUD incidence and its complications.
Proximal femoral fractures are highly prevalent in Japan, with over 200,000 cases annually and a rising trend. Fracture liaison service (FLS) interventions improve osteoporosis treatment initiation and reduce refracture rates. The content of FLS interventions varies by institution, and the effectiveness of our intervention remains unclear. The aim of this study was to evaluate the effectiveness of our FLS intervention in preventing fragility fractures within 1 year after proximal femoral fracture surgery. A retrospective case-control study was performed on patients aged ≥ 50 undergoing surgery for proximal femoral fracture between February 2021 and January 2024. Patients were divided into non-FLS (pre-August 2022) and FLS groups. Data including demographics, comorbidities, fracture type, medication initiation, and refracture occurrence within 1 year were extracted. Statistical analyses involved Mann-Whitney U, χ2 tests, and Cox proportional hazards modeling. Among 521 eligible patients, osteoporosis medication initiation within 3 months improved from 14% in the non-FLS group to 100% in the FLS group (p < 0.05). Time to medication initiation decreased from 20 to 12 days (p < 0.05). The refracture rate was significantly lower in the FLS group (1.8% vs. 5.7%, p < 0.05). Multivariate analysis showed FLS intervention significantly reduced refracture risk (HR 0.32, 95% CI 0.12-0.89, p = 0.03) and robust in sensitivity analyses for cognition, walking ability, and discharge destination. FLS intervention effectively reduced fragility fractures within 1 year postoperatively by enhancing early osteoporosis treatment initiation. Continued FLS programs and long-term follow-up are recommended to sustain benefits.
The co-occurrence of mirror-image dextrocardia and tetralogy of Fallot (TOF) is a rare congenital condition. Reoperative multivalve surgery in such patients, especially after repaired TOF, presents exceptional challenges due to the mirrored cardiac anatomy and altered surgical field. This case highlights the surgical strategy for concomitant tricuspid, mitral, and pulmonary valve replacement in this unique setting. A 14-year-old male patient with a history of corrected TOF and mirror-image dextrocardia presented with progressive heart failure due to severe regurgitation of the tricuspid, mitral, and pulmonary valves. Preoperative imaging confirmed the complex anatomy, with the atria positioned posteriorly, rendering the atrioventricular valve orifices near-vertical during surgery. The patient successfully underwent triple valve replacement under cardiopulmonary bypass. Key technical adaptations were made to select the valve model and position. The postoperative course was uneventful, with significant symptomatic and echocardiographic improvement at discharge and during the two-month and six-month follow-up. This case demonstrates that concomitant triple valve replacement is feasible in patients with mirror-image dextrocardia and a history of TOF repair, despite the profound technical challenges posed by the anatomical distortions. Success hinges on meticulous preoperative planning using advanced imaging and the development of an individualized surgical approach. This report provides a valuable reference for managing such complex, high-risk reoperations in the setting of congenital situs inversus.
The Clinical Genome Resource (ClinGen) is creating a central resource of clinically relevant genetic knowledge to improve genomic medicine. Dissemination and use of the ClinGen Resource is essential to ensure broad community uptake. We report on experiences and sustained use of ClinGen tools through engaging international genetics groups based in India, Africa and Singapore in variant classification training workshops using the ClinGen Variant Curation Interface (VCI). We developed pre and post workshop questionnaires and analyzed ClinGen tool use following the workshops. We evaluated organizational aspects and costs of creating a dedicated ClinGen VCI instance for each workshop. The workshops yielded >200 participants, with local scientists as essential participants. While ∼55% of participants were unfamiliar with variant classification, we found ∼79% were likely to use the VCI after the workshop. Further, we identified about ∼10% of workshop participants created permanent accounts. We estimate costs at ∼$3 per VCI instance. Our efforts highlight the yield of international workshops to sustained use of ClinGen's curation tools and identify areas for future consideration such as creating user-groups by experience level, and the importance of local scientist engagement in workshop deployment and organizational aspects.
This study aims to evaluate the outcomes of a new PND initiative designed to optimize healthcare delivery in a highly consanguineous population. A descriptive study was conducted at a major tertiary referral center for genetic diseases in Saudi Arabia with a large scope objective to improve the existing prenatal diagnosis (PND) process. Consequently, a new prenatal workflow featuring a structured checklist, a dedicated prenatal board, and enhanced genetic counseling has been implemented since September 2023. The study included all prenatal cases with a documented autosomal recessive (AR) disease. The program processed 1128 cases, with 952 cleared by the prenatal checklist. In total, the board has discussed 160 variants of unknown significance (VUS), of which 122 (76%) were upgraded to likely pathogenic/pathogenic. Remarkably, the prenatal checklist enhanced patient safety and reduced serious harm incidents, while the prenatal board facilitated precision medicine by leveraging collective expertise in variant interpretation. This initiative significantly improved the healthcare, safety, and accessibility of PND services. The prenatal board and checklist streamlined decision-making, minimized errors, and enhanced patient outcomes. The model provides a cost-effective approach to preventing genetic diseases in highly consanguineous populations and serves as a replicable framework for similar settings worldwide.
Rare diseases affect small, dispersed populations and are often studied through multisite designs where equity-relevant demographic data are essential for inclusive recruitment and accurate interpretation. This study examined how sociodemographic variables are collected and reported in rare disease research and evaluated their alignment with the PROGRESS-Plus framework, which outlines Place of residence, Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education, Socioeconomic status, social capital, and additional "Plus" factors such as age and disability status. A systematic review of peer-reviewed articles was conducted alongside an environmental scan of demographic instruments from governmental, health-system, academic, and rare disease organizations. Screening and extraction coded variables as reported, indirectly derivable, or not reported and compared them with established standards. Of 647 records identified, 37 met inclusion criteria. Reporting was dominated by age and sex, while most other equity-relevant variables including gender identity, sexual orientation, race/ethnicity, distinctions-based Indigenous identity, socioeconomic position, language, migration, disability/function, religion, occupation, and social capital, were inconsistently captured. Environmental scan instruments were more comprehensive, revealing a capture-to-reporting gap. Demographic reporting in rare disease research is heterogeneous and insufficient for equity-focused analyses. A concise, standards-aligned sociodemographic dataset is needed to improve transparency, comparability, and detection of inequities across rare disease populations.
Myasthenia Gravis (MG) is divided into ocular (OMG) and generalized (GMG) subtypes. While clinical diagnosis is well-established, understanding the underlying biochemical mechanisms and metabolic shifts during disease progression remains challenging; untargeted metabolomics offers a novel perspective to explore these systemic alterations. To characterize the serum metabolic landscape of MG patients and identify potential metabolic signatures associated with disease subtypes (OMG and GMG) via untargeted metabolomics. 91 participants (41 GMG, 22 OMG, 28 healthy controls [HC]) were enrolled. Fasting serum samples were analyzed by LC-MS/MS. Multivariate analyses (PCA, PLS-DA/OPLS-DA), differential metabolite screening (VIP > 1.0, p < 0.05), and KEGG pathway enrichment were performed. HC and MG groups showed distinct metabolic profiles. MG had 515 (175 up, 340 down) and 368 (146 up, 222 down) differential metabolites in positive/negative ion modes, respectively. Key perturbed pathways included glycerophospholipid, sphingolipid metabolism, and unsaturated fatty acid biosynthesis. Ten representative metabolites (e.g., ubiquinone, cortisol) differed significantly among groups; clustering analysis revealed distinct metabolite abundance trajectories across HC, OMG, and GMG. MG is associated with notable systemic metabolic dysregulation, particularly in lipid-related pathways. Rather than serving as immediate diagnostic tools, these integrative metabolic signatures provide a crucial biochemical framework for understanding disease pathogenesis and offer valuable clues for future hypothesis-driven research and prospective validation.
The association between preoperative peripheral nerve block (PNB), major adverse cardiovascular events (MACE), and postoperative length of hospital stay (LOS) in elderly patients who underwent major thoracic and abdominal surgery remains unclear. This study aims to explore the potential mediating effect of MACE on the association between preoperative PNB and postoperative LOS using a statistical mediation framework. In this retrospective cohort study, perioperative data were collected from elderly patients (aged over 65 years) who underwent major thoracic and abdominal surgery. Mediation analysis was employed to examine the relationships between PNB, MACE, and postoperative LOS. A total of 1915 patients were included in the analysis, with 68.7% (1316/1915) receiving preoperative PNB. Compared to patients who did not receive PNB, those who did had a significantly lower incidence of MACE (P < 0.001) and a shorter postoperative LOS (P < 0.001). The adjusted total and direct associations of PNB with postoperative LOS were - 0.809 days (95% confidence interval [CI], -1.236 to -0.390; P < 0.001) and - 0.661 days (95% CI, -1.077 to -0.250; P = 0.003), respectively. A statistically significant indirect association via MACE was observed (adjusted β=-0.149 days; 95% CI, -0.271 to -0.060; P < 0.001), indicating that 18.1% (95% CI, 6.7% to 41.0%) of the total association was statistically attributable to the indirect pathway through MACE under the model assumptions. A sensitivity analysis excluding postoperative covariates yielded consistent results (proportion mediated: 25.3%). Our findings suggest that the observed association between preoperative PNB and reduced postoperative LOS in elderly patients following major thoracic and abdominal surgery may be partly explained by a statistically significant indirect pathway through a reduction in MACE, potentially accounting for approximately 18% of the total effect. These findings are hypothesis-generating and represent statistical associations rather than demonstrated causal mechanisms. ChiCTR2400087610; https://www.chictr.org.cn.