Tag: pubmed

BMC Med Ethics. 2026 May 5. doi: 10.1186/s12910-026-01465-9. Online ahead of print.

ABSTRACT

BACKGROUND: Rapid Autopsy Programs (RAP) are essential research infrastructures for precision medicine, providing high-quality biospecimens. While international standards emphasize the importance of antemortem informed consent, Japan’s ethical and legal frameworks for RAP remain underdeveloped. Currently, Japan lacks a consistent approach to postmortem tissue utilization, with requirements for individual consent varying significantly between pathological autopsies, systematic dissection, and organ transplantation. This study aims to clarify Japanese public perceptions regarding the necessity of antemortem consent for RAP in comparison with these established methods to inform the development of future ethical guidelines.

METHODS: A nationwide internet survey was conducted in January 2025, involving 3,102 participants representative of the Japanese population’s sex, age, and regional distribution. Participants viewed an educational video explaining four methods of postmortem tissue utilization: pathological autopsy, RAP, systematic dissection, and organ transplantation. To prevent bias, actual names and current legal statuses were not disclosed. Respondents rated the necessity of antemortem individual consent for each method using a six-point Likert scale. Statistical analyses were performed to identify differences between methods and demographic influences.

RESULTS: The survey revealed a strong public preference for antemortem consent across all methods. Specifically, over 70% of respondents agreed that antemortem consent is necessary for pathological autopsies, and over 85% expressed the same view for RAP, systematic dissection, and organ transplantation. The results showed a marked discrepancy between Japan’s current legal system-which often relies on family consent-and public ethical awareness emphasizing individual will. While 90% valued antemortem consent for respecting individual wishes, over 50% acknowledged the difficulty of refusing a physician’s request and emphasized the importance of family intentions. Women and older adults placed significantly greater importance on antemortem consent for RAP.

CONCLUSIONS: The Japanese public maintains high expectations for individual antemortem consent that exceed current legal requirements for some procedures. However, the findings also highlight the role of “relational autonomy,” where family involvement and the clinical-research power dynamic influence decision-making. Developing an ethical framework for RAP in Japan requires not only prioritizing individual autonomy but also implementing “supported decision-making” and a clear separation between clinical and research teams to ensure social trust and cultural compatibility.

PMID:42082991 | DOI:10.1186/s12910-026-01465-9

BMC Pulm Med. 2026 May 4. doi: 10.1186/s12890-026-04332-w. Online ahead of print.

ABSTRACT

BACKGROUND: Accurate discrimination between tuberculous (TPE) and malignant pleural effusion (MPE) is a major clinical challenge. Most existing models rely on non-routine laboratory tests and lack rigorous multicenter external validation.

OBJECTIVE: To develop and validate a clinical prediction model integrating the pleural fluid adenosine deaminase to lactate dehydrogenase ratio (ADA/LDH) and routine indicators for TPE vs. MPE differentiation.

METHODS: In this multicenter retrospective study conducted between January 2023 and December 2025, patients from five hospitals in Anhui Province, China, were divided into a training cohort (n = 290), an internal validation cohort (n = 72), and an external validation cohort (n = 93). Predictors were screened via univariable analysis and backward stepwise regression based on the Akaike Information Criterion (AIC). The optimal ADA/LDH cutoff was identified as 5.83% using restricted cubic splines (RCS) and simplified to 6.0% for clinical practicability without compromising model performance. A Firth penalized logistic regression model was constructed to mitigate data separation caused by the strong predictive effect of the ADA/LDH ratio.

RESULTS: The final model included three statistically significant variables: pleural fluid ADA/LDH ratio (≥ 6.0% vs. < 6.0%), age, and sex. An ADA/LDH ratio ≥ 6.0% was the strongest independent predictor (OR = 13.32, 95% CI 6.51-27.28, P < 0.001). The model demonstrated excellent and stable discriminative ability with AUCs of 0.901 (training cohort), 0.893 (internal validation cohort), and 0.916 (external validation cohort). Calibration was good across all cohorts (Brier scores: 0.1235, 0.1249, 0.1159, respectively). Decision curve analysis demonstrated that the model provided numerically higher net benefit than the “treat all” and “treat none” strategies across the clinically relevant threshold range of 0%-90%.

CONCLUSION: This multicenter study developed and validated a robust Firth penalized prediction model centered on the pleural fluid ADA/LDH ratio. The model demonstrates excellent discriminative ability, good calibration, and potential clinical utility for differentiating TPE from MPE in TB-endemic regions of China.

PMID:42082984 | DOI:10.1186/s12890-026-04332-w

BMC Musculoskelet Disord. 2026 May 4. doi: 10.1186/s12891-026-09900-z. Online ahead of print.

ABSTRACT

BACKGROUND: The surgical rate for distal radius fractures is steadily rising despite limited evidence of its benefits over non-surgical treatment. Using a natural experimental approach, we aimed to compare patient-reported outcomes following surgical versus non-surgical treatment of distal radius fractures.

METHODS: Registered in the Swedish Fracture Register by 36 Swedish hospitals from 2013 to 2018, we included a cohort of 13,356 fractures on 13,031 patients aged 18 years or older with distal radius fractures Arbeitsgemeinschaft fur Osteosynthesefragen (AO) 23-A2.1-2, A3, and C1-C3. The observational study utilized differences in the frequency of surgical treatment across hospitals as a source of random treatment assignment and a natural experiment. We assumed that all hospitals encountered a similar range of fractures each year. Therefore, the annual frequency of surgery per hospital was used as a proxy for randomization between surgical and nonsurgical treatment, regardless of each patient’s actual treatment. The outcome was the individual Patient Reported Outcome Measures (PROM) at 1 year, with the Arm and Hand Function Index from the Short Musculoskeletal Function Assessment (SMFA) as the primary measure.

RESULTS: The surgical rate per hospital year ranged from 7 to 66%. Surgical treatment was associated with lower Arm and Hand Function Index scores in comminuted intraarticular fractures of type C2 (11.9 units, p = 0.004) and type C3 (19.4 units, p = 0.029). There was a tendency for a positive association with surgical treatment in dorsally angulated extraarticular fractures (23A2.2), but the difference of 5.1 units (p = 0.079) was below the Minimal Clinically Important Difference (MCID). In other extra-articular fractures (23-A2.1 and 23-A3) and simple intra-articular fractures (23-C1), the benefits of surgical treatment were small and also not statistically significant. Several sensitivity analyses were conducted to test the study design, and all supported the primary results.

CONCLUSIONS: In this comparison of surgical and non-surgical treatment for distal radius fractures across hospitals with varying surgical rates, comminuted intra-articular distal radius fractures (AO 23-C2/C3) treated surgically were associated with better one-year patient-reported outcomes than those treated non-surgically.

PMID:42082980 | DOI:10.1186/s12891-026-09900-z

J Cardiothorac Surg. 2026 May 4. doi: 10.1186/s13019-026-04061-5. Online ahead of print.

ABSTRACT

BACKGROUND: Intravenous drug abuse (IVDA) has increased the incidence of infective endocarditis. Standard management includes traditional open surgery and more recently described percutaneous tricuspid valve debulking. Study goals were to compare clinical outcomes and identify financial differences between percutaneous tricuspid debulking and tricuspid surgery for isolated tricuspid valve endocarditis.

METHODS: A single-center, retrospective cohort patient study of isolated tricuspid valve endocarditis was performed. Patients underwent either percutaneous debulking with the AngioVac system (n=14, 83% IVDA) or tricuspid valve surgery (n=23, 76% IVDA). Length of stay, readmission rates, mortality, echocardiographic parameters, hematologic markers, transfusion rates, and total charges for index hospitalization were evaluated between groups.

RESULTS: In patients who underwent either percutaneous debulking or open surgery, length of stay (17±17 vs 20±13 days, p=0.48), 30-day readmission (29% vs 26%, p=0.87), in-hospital mortality (7% vs 0%, p=0.20), and 30-day mortality (7% vs 0%, p=0.20) were not statistically different. One-year mortality (21% vs 4%, p=0.11) trended toward but did not reach significance. Postoperative tricuspid valve regurgitation (2.5±1.1 vs 1.0±0.3, p<0.0001) and transfusion rates (2±3 vs 6±6 units, p=0.02) were significantly different between therapies. Total charges for hospitalization were not statistically different ($557,066±457,520 vs $571,615±324,254, p=0.91).

CONCLUSIONS: Tricuspid debulking is a potential alternative to surgery for patients with infective tricuspid endocarditis. Similar outcomes, costs, and avoidance of prosthetic material in patients with active IVDA are potential benefits.

PMID:42082977 | DOI:10.1186/s13019-026-04061-5

BMC Palliat Care. 2026 May 4. doi: 10.1186/s12904-026-02132-x. Online ahead of print.

ABSTRACT

BACKGROUND: Early integration of pediatric palliative care (PPC) improves symptom control, communication, and goal-concordant decision-making. Despite these benefits, PPC remains underutilized in many Asian healthcare systems, where referrals are often delayed and most children die in intensive care units (ICUs).

METHODS: This retrospective cohort study included children aged 0-18 years who died between 2008 and 2017 at two medical centers in southern Taiwan (n = 294). A shared PPC program was implemented in 2011, embedding palliative specialists within primary care teams. Documentation of do-not-resuscitate (DNR) orders, family meetings, PPC consultations, cardiopulmonary resuscitation (CPR), and place of death were compared across pre-implementation, early post-implementation, and late post-implementation phases.

RESULTS: Following implementation, DNR documentation increased from 59.2% to 73.9% (p = .03). Documented family meetings rose from 4.1% to 18.2% (p < .001), and PPC consultations increased from 7.1% to 23.9% (p < .001), suggesting potential improvements in interdisciplinary communication and advance care planning. ICU deaths remained high (87.8%-89.8%), and CPR rates declined but did not reach statistical significance (p = .09). Cancer diagnosis (OR = 7.97, 95% CI 2.71-23.42) and increasing age at diagnosis (OR = 1.12 per year, 95% CI 1.06-1.18) were independently associated with PPC consultation.

CONCLUSIONS: Integration of a shared PPC model was associated with improvements in advance care planning and interdisciplinary collaboration. Earlier referral triggers, clinician education, and expansion of community-based PPC services may be important to help reduce high-intensity end-of-life care and better align care delivery with family preferences.

PMID:42082973 | DOI:10.1186/s12904-026-02132-x

J Exp Clin Cancer Res. 2026 May 4. doi: 10.1186/s13046-026-03716-4. Online ahead of print.

ABSTRACT

BACKGROUND: Immunotherapy has emerged as a promising strategy for multiple myeloma (MM), yet relapse remains frequent due to the immunosuppressive bone marrow (BM) microenvironment, characterized by T cell dysfunction and accumulation of immunosuppressive myeloid cells. The co-stimulatory receptor 4-1BB (CD137, TNFRSF9) can enhance T and NK cell effector functions, but its therapeutic utility in MM is not well established. Tasquinimod (TQ), a clinical-stage S100A9 inhibitor, offers a complementary approach by limiting the recruitment and activity of suppressive myeloid cells.

METHODS: 4-1BB expression was assessed during disease progression in MM mice and in newly diagnosed MM patients using single-cell RNA sequencing and flow cytometry. Therapeutic potential was evaluated in 5TGM1 tumor-bearing mice treated with two 4-1BB agonists, LOB12.3 (IgG1κ) and 3H3 (IgG2a), using isotype controls. The lead agonist was subsequently combined with TQ to investigate dual targeting of the immunosuppressive tumor microenvironment. Tumor burden was quantified via BM and spleen plasmacytosis and serum M-protein levels. Immune modulation was analyzed using multi-parameter flow cytometry. Statistical significance was determined using the Mann-Whitney U test or one-way ANOVA (p < 0.05).

RESULTS: 4-1BB expression progressively increased on T and NK cells during tumor development in mice. In primary MM patient BM samples, ex vivo 4-1BB stimulation with urelumab enhanced effector responses, increasing IFN-γ⁺ and Granzyme B⁺ CD3⁺ T cells, alongside trends toward increased CD56⁺ NK cells and elevated IFN-γ⁺ NK cell activity. In vivo, 4-1BB agonist treatment promoted expansion of T cell subsets, with clone-specific effects: the IgG2a clone 3H3 significantly reduced M-protein levels and BM plasmacytosis, whereas the IgG1 clone LOB12.3 induced NK cell depletion and demonstrated limited anti-tumor activity. Combining 3H3 with TQ provided superior anti-myeloma efficacy, reducing BM plasmacytosis from 62.5% in controls to 14.1% under combination treatment. Mechanistically, the combination enhanced Granzyme B expression, effector T cell differentiation, and dendritic cell maturation (CD86 upregulation), collectively overcoming BM immunosuppression.

CONCLUSIONS: These findings establish the isotype-specific efficacy of 4-1BB agonists and support 4-1BB stimulation combined with TQ as a promising strategy to enhance durable immunotherapeutic responses in MM.

PMID:42082972 | DOI:10.1186/s13046-026-03716-4

BMC Med Educ. 2026 May 5. doi: 10.1186/s12909-026-09354-w. Online ahead of print.

ABSTRACT

BACKGROUND: Medical emergencies during dental procedures are not uncommon. Given the high-risk nature of dentistry and the necessity for immediate patient management, this study aimed to evaluate the effectiveness of a targeted educational intervention by expanding assessment parameters for knowledge and performance, including follow-up evaluations.

METHODS: This educational interventional study was conducted in 2023 with 60 senior dental students recruited via an open call. Participants were randomly assigned to intervention and control groups using a random number table. All participants underwent a theoretical and practical assessment based on the American Heart Association (AHA) standardized examination. The intervention group participated in a hands-on emergency medicine and resuscitation workshop, followed by theoretical and practical assessments at one- and three-months post-intervention. Data were analyzed using SPSS version 26. Independent t-tests and ANCOVA were used for between-group comparisons, while repeated measures ANOVA and LSD post hoc tests were applied for within-group analyses. A significance level of 0.05 was adopted.

RESULTS: The mean scores from the workshop questionnaire at baseline, immediately post-intervention, and at one- and three-month follow-ups showed a statistically significant improvement over time in the intervention group (p < 0.001), while no significant change was observed in the control group (p = 0.808). Similarly, practical exam scores demonstrated a significant time-dependent improvement in the intervention group (p < 0.001), with no meaningful change in the control group (p = 0.999).

CONCLUSION: The emergency medicine workshop-covering both basic and advanced resuscitation-significantly enhanced the theoretical knowledge and practical skills of senior dental students. Moreover, the sustained impact observed over time underscores the long-term value of such educational interventions.

PMID:42082971 | DOI:10.1186/s12909-026-09354-w

BMC Pulm Med. 2026 May 4. doi: 10.1186/s12890-026-04319-7. Online ahead of print.

ABSTRACT

BACKGROUND: Asthma is a heterogeneous disease, underscoring the urgent need for reliable diagnostic biomarkers. Vanin-1, a well-recognized sensor of oxidative stress, has been implicated in various inflammatory disorders; however, its diagnostic value in asthma remains to be fully elucidated. This study aimed to evaluate serum Vanin-1 levels in asthmatic patients and explore their correlations with systemic oxidative stress biomarkers-malondialdehyde (MDA) and glutathione (GSH)-as well as inflammatory cytokines, pulmonary function parameters, and to assess its diagnostic potential.

METHODS: A case-control study was conducted, enrolling 169 participants: 129 asthmatic patients and 40 age- and sex-matched healthy controls. Serum concentrations of Vanin-1, MDA, GSH, cytokines (IL-4, IL-13, IL-17, IFN-γ), and total IgE were measured. Pulmonary function tests were also performed. Statistical correlations were analyzed using Spearman’s rank test, and diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curves.

RESULTS: Compared with healthy controls, asthmatic patients exhibited significantly elevated serum levels of Vanin-1 (7.54 ± 1.62 ng/mL vs. 4.59 ± 1.30 ng/mL, P < 0.001) and MDA [0.11 (0.09, 0.12) nmol/mg protein vs. 0.08 (0.06, 0.10) nmol/mg protein, P < 0.001], but markedly reduced GSH [1.44 (1.16, 1.57) nmol/mg protein vs. 2.06 (1.65, 2.37) nmol/mg protein, P < 0.001]. Vanin-1 level was positively correlated with MDA (ρ = 0.342, P < 0.001) and negatively correlated with GSH (ρ = – 0.329, P < 0.001). No significant correlations were observed between Vanin-1 and IL-4, IL-13, IL-17, IFN-γ, eosinophil counts, or pulmonary function indices. ROC analysis demonstrated that Vanin-1 had robust diagnostic utility, with an area under the curve (AUC) of 0.884 (95% CI: 0.832-0.936, P < 0.001). At an optimal cutoff of 6.12 ng/mL, the sensitivity and specificity were 69.0% and 92.5%, respectively.

CONCLUSION: Serum Vanin-1 is significantly elevated in asthmatic patients and is closely associated with an oxidative stress imbalance. It may serve as a potential biomarker for distinguishing asthma patients from healthy individuals.

PMID:42082969 | DOI:10.1186/s12890-026-04319-7

BMC Musculoskelet Disord. 2026 May 4. doi: 10.1186/s12891-026-09838-2. Online ahead of print.

ABSTRACT

BACKGROUND: Differentiating between spinal tuberculosis, pyogenic (bacterial) spondylitis and spinal metastasis remains a major diagnostic challenge because their radiological features often overlap. Delayed or incorrect diagnosis may lead to inappropriate treatment, permanent disability or death.

OBJECTIVE: To develop and evaluate deep learning models for automated classification of spinal tuberculosis, pyogenic infection, and spinal metastasis using magnetic resonance imaging (MRI).

METHODS: T2-weighted sagittal MRI scans from 120 patients (40 per disease group) with pathologically or microbiologically confirmed diagnoses between 2014 and 2019 were retrospectively analyzed. Lesion regions were manually annotated by radiologists, and data were split into 80% training and 20% testing sets at the patient level. Extensive data augmentation (rotation ± 5°, zoom 1.1-1.2×, shearing ± 5°, grid distortion 2 × 2) was applied to mitigate overfitting. Three models were trained and compared: (1) a single-layer perceptron baseline, (2) a custom dense neural network (2 × 1024 neurons), and (3) pre-trained convolutional neural networks (ResNet50, VGG16, InceptionV3). Model performance was evaluated using accuracy, precision, recall, and F1-score on both whole and segmented images.

RESULTS: After augmentation, 1,000 synthetic samples were generated per class. The baseline model achieved 27-33% accuracy, whereas the dense and pre-trained models achieved 98-100% accuracy on the test set. Although pre-trained networks demonstrated marginally higher performance, the difference compared with the dense model was not statistically significant. Activation heatmaps revealed inconsistent localization of attention regions, suggesting potential overfitting and limitations in visualization interpretability.

CONCLUSION: Deep learning models demonstrated strong potential in distinguishing between spinal tuberculosis, bacterial spondylitis, and spinal metastasis on MRI. However, the near-perfect performance likely reflects dataset homogeneity and augmentation effects rather than full generalization. External, multi-center validation and improved interpretability methods (e.g., Grad-CAM) are warranted to confirm clinical applicability and ensure reliable decision support for radiologists.

PMID:42082966 | DOI:10.1186/s12891-026-09838-2

BMC Psychiatry. 2026 May 4. doi: 10.1186/s12888-026-08136-4. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) is a prevalent degenerative neurological disorder with limited treatment options. Prior studies reported specific metabolites and inflammatory proteins to be related to AD risk. However, the intricate relationship between inflammatory proteins, blood metabolites, and AD risk in European population remains unclear. Genetic instruments for 1,091 metabolites and 736 inflammatory proteins were derived from two recent comprehensive genome-wide association studies. Univariable Mendelian Randomization was employed to assess potential causal effects of metabolites on AD risk, potential effects of inflammatory proteins on metabolites, and effects of inflammatory proteins on AD risk. Multivariable MR (MVMR) was further applied to disentangle direct effects of proteins and metabolites on AD. Twelve metabolites were identified to be associated with AD risk, and 226 inflammatory proteins demonstrated likely to be causal effects on these 12 metabolites. Further examining the associations between such inflammatory proteins and AD risk revealed 22 associations for which the effect directions from inflammatory proteins to metabolites, from metabolites to AD risk, and from inflammatory proteins to AD risk were aligned, suggesting inflammatory protein – metabolite – AD risk pathway. MVMR further highlighted four trios in which the effect directions were consistent with the UVMR results, supporting a metabolite‑mediated pattern. This large‑scale genetic analysis highlights specific metabolites as direct contributors to AD risk and suggests that certain inflammatory proteins may influence AD primarily through downstream metabolic pathways. Our findings offer potential novel therapeutic targets for AD intervention.

PMID:42082960 | DOI:10.1186/s12888-026-08136-4