BackgroundFunctional recovery after ischemic stroke varies substantially across patients and stages of care. Conventional rehabilitation planning relies mainly on clinical scales and physician judgment, which may not fully capture the nonlinear interactions among neurological severity, functional status, comorbidities, treatment exposure, and rehabilitation stage. This study aimed to develop and internally validate an artificial intelligence-driven precision rehabilitation model for predicting poor rehabilitation outcome across the continuum of care in patients with ischemic stroke.MethodsIn this retrospective cohort study, 268 patients with ischemic stroke were divided into a training cohort (n = 188) and an internal validation cohort (n = 80) using stratified random sampling to preserve the outcome distribution. Candidate predictors included demographic characteristics, vascular risk factors, comorbidity burden, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline Modified Barthel Index (MBI) score, rehabilitation stage, and treatment-related variables. Poor rehabilitation outcome was defined as an MBI score below 85 or a reduction in NIHSS score of less than 2 points during the observation period. Logistic regression, random forest, extreme gradient boosting (XGBoost), and Light Gradient Boosting Machine models were developed and compared. Model performance was evaluated using discrimination, calibration, decision curve analysis, and SHapley Additive exPlanations.ResultsPoor rehabilitation outcome occurred in 104 patients (38.8%). In the internal validation cohort, XGBoost showed the best overall performance, with an area under the receiver operating characteristic curve of 0.862 (95% CI, 0.776–0.923), accuracy of 0.813, sensitivity of 0.806 (95% CI, 0.625–0.926), specificity of 0.816 (95% CI, 0.679–0.912), F1 score of 0.781, and Brier score of 0.139. Calibration analysis showed acceptable agreement between predicted and observed risks. Decision curve analysis indicated greater net clinical benefit than treat-all or treat-none strategies across threshold probabilities of 0.20–0.75. SHAP analysis identified baseline MBI score, baseline NIHSS score, age, structured rehabilitation therapy, rehabilitation stage, and comorbidity burden as the most influential predictors. Model-derived low-, intermediate-, and high-risk groups showed poor outcome rates of 12.8%, 34.4%, and 68.6%, respectively.ConclusionThe proposed artificial intelligence-driven model showed favorable discrimination, acceptable calibration, and clinically meaningful risk stratification for ischemic stroke rehabilitation. It may provide a preliminary framework for individualized rehabilitation risk stratification across the continuum of care; however, external multicenter validation and prospective clinical evaluation are required before routine clinical application.
BackgroundPatients with rheumatoid arthritis (RA) and high levels of Rheumatoid Factor (RF) often present with a higher inflammatory burden and may show a reduced response to JAK inhibitors (JAKi). However, previous studies have demonstrated that certolizumab pegol (CZP) provides comparable efficacy in patients regardless of RF level.ObjectivesTo compare the effectiveness and treatment retention of CZP versus JAKi in patients with RA according to baseline RF levels, assessing (a) changes in disease activity at 6 and 12 months, and (b) treatment retention over a 3-year follow-up period.MethodsThis multicentre retrospective cohort included RA patients initiating CZP or JAKi (baricitinib, filgotinib, tofacitinib, upadacitinib) between 2010 and 2024. Patients were stratified by baseline RF levels (RF < 189 IU/mL and RF ≥ 189 IU/mL). Disease activity was assessed using DAS28-ESR at baseline, 6, and 12 months. Drug retention was analysed using Cox regression models, with a 3-year follow-up. A sensitivity analysis using IPTW was performed to account for baseline differences, while MICE and MNAR sensitivity analysis addressed missing data and informative missingness.ResultsThe study included 370 RA patients (409 treatment episodes: 234 CZP, 175 JAKi). Among patients with RF ≥ 189 IU/mL, CZP was associated with a greater reduction in DAS28-ESR than JAKi at both 6 and 12 months, with statistically significant differences at 12 months. In contrast, among patients with RF < 189 IU/mL, a greater reduction in DAS28-ESR at 6 months was observed in the JAK inhibitor group. CZP also demonstrated substantially higher drug retention at 3 years. In IPTW-weighted analyses, CZP was associated with a greater improvement in disease activity at 12 months in patients with RF ≥189 IU/mL, while treatment retention was numerically higher with CZP than with JAKi in this subgroup. However, the 12-month difference in clinical efficacy did not remain statistically significant under the MNAR sensitivity analysis.ConclusionThis study suggests that CZP may be associated with greater improvement in disease activity at 12 months in patients with RA and high RF levels, although this finding did not remain statistically significant under the MNAR sensitivity analysis and should therefore be interpreted with caution. A numerical difference in treatment retention favouring CZP was also observed. These findings highlight the potential importance of considering RF levels when selecting treatment and warrant further investigation in prospective studies.
ObjectiveThis study aimed to investigate the predictive value of the disseminated intravascular coagulation (DIC) score combined with lactate (Lac) for the prognosis of patients with cirrhosis and variceal upper gastrointestinal bleeding (VUGIB).MethodsIn this retrospective cohort study, we enrolled 409 patients with liver cirrhosis and VUGIB who were admitted to Beijing You'an Hospital, Capital Medical University, between July 2023 and July 2025.The predictive outcomes were 28-day mortality, multiple organ dysfunction syndrome (MODS), and admission to the intensive care unit (ICU). Univariate baseline comparisons were performed. A multivariable logistic primary model was constructed, and two types of sensitivity analyses were established. The independence of the DIC score as a prognostic factor was assessed using Wald, likelihood-ratio, and interaction tests. Receiver operating characteristic (ROC) curves were plotted, and the areas under the curves (AUCs) of the models were compared using DeLong's test. Internal validation was conducted with 1,000 bootstrap resamples. Model calibration was evaluated using the Hosmer-Lemeshow test and calibration curves. The optimal cut-off value was determined via 10-fold cross-validation, and survival differences were analyzed using the Kaplan–Meier method. Decision curve analysis was performed to evaluate the net clinical benefit.ResultsUnivariate analysis revealed that lactate, DIC score, and various liver function and bleeding scores differed significantly among the three prognostic outcome groups (all P < 0.05). After adjusting for covariates, DIC score was identified as an independent risk factor for all three outcomes, and its predictive value was independent of Child-Pugh and MELD-Na scores, with no interaction between them. ROC analysis showed that the combined lactate + DIC model had the best discriminative performance (AUC for mortality = 0.892, for MODS = 0.889, for ICU admission = 0.851), and DeLong's test confirmed that it was superior to most conventional scores. After bootstrap correction, the model exhibited no significant optimism bias, and the Hosmer-Lemeshow test indicated good calibration. Stratification by the cross-validation-derived cutoff value revealed statistically significant differences in 28-day survival between high-and low-risk patients across all outcome groups (log-rank P < 0.001). Decision curve analysis demonstrated that the lactate + DIC model provided higher net clinical benefit than DIC score alone. ConclusionThe combination of DIC score and lactate independently predicts the risks of 28-day mortality, MODS, and ICU admission in patients with liver cirrhosis and VUGIB. Multidimensional validation demonstrated that this model exhibited superior discrimination, calibration, and net clinical benefit compared with any single score, and thus can be applied for early risk stratification at admission.
Surgically induced acute kidney injury (AKI) may involve both ischemia–reperfusion and direct mechanical damage to the renal parenchyma, potentially affecting subsequent tissue repair and remodeling. Although bone morphogenetic protein-7 (BMP-7) has shown renoprotective effects in experimental models of acute kidney injury, most studies have evaluated systemic administration in relatively homogeneous injury models. The effects of local BMP-7 delivery in the setting of combined ischemic and surgical parenchymal injury remain insufficiently defined. In this study, a rat model combining transient renal ischemia–reperfusion with a standardized parenchymal incision was used to investigate renal repair following surgical injury. Recombinant human BMP-7 (rhBMP-7) was applied locally to the injured renal parenchyma using Surgicel as a carrier. Serum renal function measures, tubular injury, proliferative activity, fibrosis-associated remodeling, and selected repair- and BMP-associated signaling markers were evaluated at 7 and 28 days after injury. Local Surgicel/rhBMP-7 application was associated with lower serum blood urea nitrogen and creatinine levels at day 7 compared with the suturing-only surgical-injury group. Histopathological tubular injury was observed in both groups, without significant between-group differences. Increased numbers of proliferating cell nuclear antigen (PCNA)-positive tubular epithelial cells were observed in the Surgicel/rhBMP-7 group at both analyzed time points. Compared with the suturing-only group, the Surgicel/rhBMP-7 group showed higher Wnt-4 immunoreactivity at both time points and higher phosphorylated Smad1/5/8 immunoreactivity at day 28, compatible with differences in BMP-associated signaling. Histological analysis demonstrated a reduced collagen-positive area in the Surgicel/rhBMP-7 group, accompanied by a time-dependent pattern of α-SMA expression. In conclusion, local Surgicel/rhBMP-7 delivery was associated with differences in functional, tubular proliferative, repair-associated signaling, and histological remodeling responses following combined renal ischemia–reperfusion and surgical parenchymal injury. These findings support further evaluation of this localized delivery approach in more comprehensively controlled models of surgical kidney injury.
Deep models for oral squamous cell carcinoma (OSCC) detection from haematoxylin-eosin histopathology degrade sharply across laboratories, scanners and magnifications, yet the target centre is usually unavailable during training, making generalization to unseen domains the decisive requirement for reliable screening. We cast multi-centre OSCC classification as a domain-generalization problem and propose SICA (Style-Invariant Consistency Alignment), a single objective combining three established invariance mechanisms: style randomisation of channel-wise feature statistics, a stain-consistency term forcing two independently stained views of each image to agree in embedding and prediction space, and a class-conditional feature alignment that preserves the decision boundary. Two of them rely only on paired stain views, so SICA remains effective with a single source domain, where classical cross-domain alignment collapses to plain risk minimisation. On a reproducible leave-one-domain-out benchmark spanning a genuine cross-magnification shift and a controlled multi-centre stain-shift simulation, SICA is compared against nine baselines over eight metrics. Among the ten algorithms sharing a common ImageNet backbone it attains the best and most stable out-of-domain AUROC (90.6% on the multi-centre protocol), the best worst-case centre, and a balanced operating point better calibrated than empirical risk minimisation. With confidence intervals, paired tests and multiplicity correction, that margin over the strongest baselines proves consistent but not statistically decisive on five simulated centres. Under the same protocol, a frozen pathology foundation model closes part of the stain gap but not the scale gap, and the proposed objective improves it further (92.3% to 93.4% AUROC on identical frozen features), so better representations and explicit invariance are complementary. An audit of the public corpus uncovered 28 byte-identical images filed under contradictory labels, removed before re-running the benchmark under a group-aware, leakage-controlled protocol. Finally, on a genuinely independent 150-patient cohort we report a negative result: every method, ours included, falls to chance-level discrimination, because the binding constraint is field-of-view scale rather than stain. Stain invariance is therefore necessary but not sufficient, and a simulated stain-shift benchmark must not be read as an estimate of deployment performance.
A 52-year-old man presented with severe irritative lower urinary tract symptoms. Cystoscopy revealed extensive scattered papillary tumor-like lesions, mainly involving the lateral and posterior bladder walls. Computed tomography urography (CTU) showed bladder-wall thickening and reduced bladder capacity. Endoscopic biopsy and transurethral resection of bladder tumor (TURBT) were performed on two occasions; both histopathological examinations demonstrated suppurative inflammation, marked acute and chronic inflammatory cell infiltration, granulation-tissue proliferation, and focal lymphoid hyperplasia. Empirical antituberculous therapy was administered for suspected tuberculosis, but the irritative symptoms persisted. Repeat cystoscopy 6 months later again demonstrated extensive scattered papillary tumor-like lesions. Another TURBT was performed, and subsequent pathological consultation established the diagnosis of bladder nephrogenic adenoma. During follow-up, bladder capacity continued to decline, and retrograde cystography demonstrated left vesicoureteral reflux after instillation of only 30 mL of contrast medium. Because bladder contracture severely impaired quality of life, radical cystectomy with orthotopic ileal neobladder substitution was ultimately performed. At 3 months postoperatively, the voiding interval had increased to 1–2 h, nocturia had decreased to approximately three episodes per night, and the perineal radiating pain had resolved, without significant urgency or urinary incontinence.
BackgroundAntisynthetase syndrome (ASyS) is a distinct subtype of idiopathic inflammatory myopathy (IIM), characterized by multisystem involvement, including the lungs, skin, skeletal muscles, and joints, as well as the presence of anti-aminoacyl-tRNA synthetase (ARS) antibodies. While 8% to 30% of patients present with classic dermatomyositis-like rashes, atypical skin involvement can also occur. Rarely, patients may develop cutaneous edema that mimics cellulitis, which is highly susceptible to misdiagnosis.Case presentationA 72-year-old woman presented with a 1-week history of erythema, swelling, and pain in the right lower limb. Physical examination showed marked edema with a peau d’orange appearance, local warmth, and tenderness. Given the detection of fungal hyphae on the right foot, cellulitis was initially suspected. However, the lesions did not improve after 5 days of cefuroxime sodium treatment, and she developed right gastrocnemius tenderness, markedly elevated muscle enzymes, and interstitial changes on chest computed tomography. Myositis antibody testing was positive for anti-melanoma differentiation-associated gene 5(anti-MDA5) and anti-histidyl-tRNA synthetase(anti-Jo-1) antibodies. Right gastrocnemius biopsy showed fiber-size variation and scattered endomysial inflammatory infiltration, without necrosis or perifascicular atrophy; immunohistochemistry showed focal/patchy major histocompatibility complex class I (MHC-I) expression and weak non-perifascicular sarcoplasmic myxovirus resistance protein A (MxA) positivity. Antisynthetase syndrome was diagnosed. Moderate-dose oral prednisone was added and cefuroxime sodium was discontinued. Eight days later, erythema, swelling, and myalgia improved, with marked decreases in muscle enzymes and hypersensitive C-reactive protein(hs-CRP). After discharge, mycophenolate mofetil(MMF) and nintedanib were added. Three months later, the skin lesions had completely resolved, creatine kinase, lactate dehydrogenase, high-sensitivity troponin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) nearly normalized; interstitial lung disease (ILD) improved, and pleural/pericardial effusions markedly decreased.DiscussionNotably, this case highlights that ASyS may mimic infectious cellulitis and cause misdiagnosis. Inflammatory myopathy should be considered when atypical skin lesions are accompanied by elevated muscle enzymes and ILD.
IntroductionThe associations between gut microbiota and disease progression, as well as the prognostic implications of gut microbiota, remain unclear in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs). This study aimed to delineate gut microbiome differences among ICI-treated patients with intermediate-to-advanced HCC and assess their correlations with clinical outcomes via meta-analysis.MethodsWe searched 4 databases (PubMed, Embase, Web of Science, and the Cochrane Library) and collected related articles published before May 31, 2026. We calculated standard mean differences (SMDs) and 95% confidence intervals (CIs) using a random-effects model. Summarized hazard ratios (HRs) with 95% CIs were used to assess gut microbiome associations with overall survival (OS) and progression-free survival (PFS). Subgroup, sensitivity, and publication bias analyses were further conducted, with all statistical analyses performed using RevMan and R.ResultsA total of 13 eligible papers were included. (1) The meta-analysis of Alpha diversity indices between R and NR was no significant difference, but over 68% of the studies reported significant differences in beta diversity. (2) At the phylum level, Actinobacteriota were significantly enriched in the R group. At the genus level, depleted Bacteroides exhibited distinct relative abundance in the NR group. (3) Protective taxa (Collinsella, Ruminococcus.AF25_28AC, Ruminococcus.AM42_11, Erysipelotrichaceae bacterium-GAM147, Bacteroides stercoris/Parabacteroides merdae) correlated with reduced mortality risk. Risky taxa (Bacteroides.AF20_13LB, Veillonella.atypica, Veillonella.AF13_2, Veillonellaceae and s_Actinomyces_sp_ICM47) showed worse OS outcomes. (4) PFS-protective taxa (Collinsella, Bacteroidales zoogleoformans, Ruminococcus.AF25_28AC, Ru-minococcus callidus, and Erysipelotrichaceae bacterium GAM147) correlated with reduced progression risk. PFS-detrimental taxa (Prevotella 9, Bacteroides_AF20_13LB, Veillonella atypica, and Lachnoclostridium) showed worse outcomes. (5) Responders showed upregulated bile acid metabolism, fatty acid biosynthesis, methanogenesis and carbon fixation pathways associated with beneficial genera, while non-responders exhibited elevated secondary bile acid metabolism, arginine biosynthesis and carbohydrate transport pathways linked to detrimental taxa.ConclusionsHCC patients with varied treatment responses exhibit characteristic shifts in gut flora. Compositional and functional variations of intestinal microbes serve as potential indicators of disease status, promising prognostic predictors, and references for clinical therapeutic decisions.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO CRD420261363281.
BackgroundMycobacterium abscessus (M. abscessus), a rapidly growing non-tuberculous mycobacterium (NTM), rarely causes extrapulmonary disease involving more than one serosal compartment.Case presentationAn 83-year-old man developed intermittent fever about 6 weeks after coronary stent implantation. Multiple antibiotics were ineffective, and he was admitted for fever of unknown origin. Echocardiography showed newly developed pericardial adhesion with echocardiographic changes suggestive of possible early constrictive physiology. These were absent on the echocardiogram performed on the day of percutaneous coronary intervention. During admission, he underwent surgery for mechanical small-bowel obstruction, in which dense omental adhesions were found. With no prior abdominal surgery, the synchronous pericardial, pleural, and peritoneal abnormalities raised suspicion of a systemic inflammatory or infectious process. A single blood-culture draw at the outside hospital grew coagulase-negative staphylococcus, but blood cultures repeated after admission and a bone-marrow culture were negative. Blood metagenomic next-generation sequencing (mNGS) detected M. abscessus at very low abundance (three species-level reads, below the ≥8-read threshold), reported as a suspected organism. Temperature improved during the administration of agents with recognized activity against M. abscessus (linezolid, tigecycline) and relapsed during the administration of β-lactams not active against this organism. Integrating the clinical course, treatment response, and consultation from a tuberculosis specialty hospital, a clinically suspected diagnosis of M. abscessus infection supported by mNGS was made, although microbiological confirmation was not obtained. Temperature normalized on tigecycline and the patient’s condition improved, and he was transferred for continued anti-NTM therapy. He was subsequently lost to follow-up, and therefore, the long-term outcome is unknown.ConclusionWe report a rare presentation of suspected M. abscessus-associated polyserositis following coronary stenting, in which mNGS provided the etiologic clue when cultures were unrevealing. NTM should be considered in older patients with unexplained fever after cardiovascular intervention. Low-abundance mNGS results, although below reporting thresholds, may be clinically meaningful when interpreted alongside the clinical course and treatment response, while remaining open to contamination and misclassification. NTM-associated myeloperoxidase-antineutrophil cytoplasmic antibody positivity is non-specific and must be distinguished from primary vasculitis.
ObjectiveTo explore the predictive value of nutritional status combined with Probable sarcopenia assessment for all-cause readmission of elderly inpatients with multimorbidity within 90 days after discharge.MethodsIn this single-centre retrospective cohort study, a total of 244 patients aged ≥65 years admitted to our hospital from January 2023 to March 2025 were selected as the research subjects. Abnormal nutritional status (malnutrition or risk of malnutrition, MNA-SF ≤11) and probable sarcopenia (per modified EWGSOP2-based criteria) were assessed within 48 h of admission, and patients were divided into a readmission group (59 cases) and a non-readmission group (185 cases) according to whether they were readmitted within 90 days after discharge.ResultsThe age of patients in the readmission group was significantly higher than that in the non-readmission group (P < 0.05), the Charlson Comorbidity Index was higher (P < 0.05), the level of C-reactive protein was higher (P < 0.05), and the serum albumin, handgrip strength and calf circumference were lower (P < 0.05). The overall prevalence of probable sarcopenia was 31.1%, and the prevalence of malnutrition (including risk) was 73.8%. Abnormal nutritional status was defined as MNA-SF ≤11 (combining at-risk and malnourished categories). The combined group analysis showed that the 90-day readmission rate of patients with abnormal nutritional status and probable sarcopenia (Group D) was the highest, reaching 47.8%, which was significantly higher than that of other groups (P < 0.05). Multivariate logistic regression analysis showed that after adjusting for age, sex, comorbidities and inflammatory markers, the combined status was independently associated with higher odds of 90-day readmission (aOR=3.94, 95%CI: 1.73–8.96, P = 0.001). The combined assessment model demonstrated moderate discriminative ability (AUC 0.724, 95% CI: 0.651–0.797), which was statistically significantly better than that of nutrition or probable sarcopenia assessment alone (DeLong P < 0.05).ConclusionIn this single-center retrospective cohort, the coexistence of abnormal nutritional status (MNA-SF ≤11) and probable sarcopenia was independently associated with higher odds of 90-day readmission in elderly hospitalized patients with multimorbidity. Larger prospective multicenter studies are needed to validate the combined assessment and determine whether targeted interventions reduce readmission.
BackgroundShoulder arthroplasty is a well-established surgical intervention for osteoarthritis, rotator cuff arthropathy, and complex shoulder diseases. While effective in pain relief and functional improvement, perioperative complications remain a major concern. Patients with diabetes present metabolic disturbances and suboptimal glycemic control, conferring higher risks of adverse perioperative events. Nevertheless, evidence regarding the impact of diabetes subtypes on short-term perioperative outcomes after shoulder arthroplasty remains scarce. This study employed the U.S. National Inpatient Sample (NIS) database to explore the association between diabetes subtypes and perioperative outcomes following shoulder arthroplasty.MethodData were derived from the National Inpatient Sample (NIS) database from 2016 to 2022. Patients undergoing shoulder arthroplasty were included and classified into three groups: patients with type 1 diabetes mellitus (T1DM), patients with type 2 diabetes mellitus (T2DM), and patients without diabetes. Patient demographics, hospital characteristics, surgical parameters, comorbidities, perioperative complications, and postoperative outcomes were assessed. Propensity score matching was applied to balance baseline characteristics between groups. Regression analyses were conducted to evaluate postoperative outcomes among patients with different DM subtypes.ResultA total of 137,651 shoulder arthroplasty cases were identified, comprising 107,388 patients without diabetes, 376 patients with type 1 DM, and 29,887 patients with type 2 DM. Following propensity score matching, multivariate analysis demonstrated no significant between-group differences in most medical and surgical complications when comparing patients without diabetes and patients with type 1 DM. In contrast, type 2 DM was identified as an independent risk factor for pneumonia/acute respiratory failure (OR = 1.19, P < 0.001), surgical site/periprosthetic joint infection (OR = 1.25), urinary tract infection (OR = 1.25), acute renal failure (OR = 1.53), non-routine discharge (OR = 1.34), prolonged length of stay (GMR = 1.04), and increased total hospital charges (GMR = 1.02).ConclusionCompared with patients without diabetes, patients with type 2 DM undergoing shoulder arthroplasty exhibited higher risks of several adverse in-hospital outcomes, whereas most outcomes in patients with type 1 DM were not significantly different. These findings may facilitate improved risk stratification and tailored perioperative management.
ObjectiveThis study seeks to develop and compare four machine learning models using the MIMIC-IV database to identify predictive variables associated with invasive mechanical ventilation (MV) requirement in patients with embolic cerebral infarction.MethodsThis study included 568 patients with embolic cerebral infarction from the MIMIC-IV database. Data collected encompassed demographic information, vital signs, laboratory results, and other relevant variables. The dataset was randomly split into a development set and a validation set in a 7:3 ratio. Feature selection was performed using univariable and multivariable analyses. Four prediction models, namely decision tree (DT), logistic regression (LR), eXtreme Gradient Boosting (XGB), and Light Gradient Boosting Machine (LGBM), were developed. Model performance was assessed using receiver operating characteristic (ROC) curve analysis. Calibration was evaluated through calibration curves and Brier scores. Clinical utility was examined using decision curve analysis (DCA), and Shapley additive explanations (SHAP) were used to interpret model predictions. ICU admission was t0 and predictors were summarized over the first 24 h. Because exact MV-initiation times were unavailable, robustness analyses addressed optimism, class imbalance, and temporal ambiguity using repeated nested cross-validation, an all-MV benchmark, inverse-frequency weighting, and exclusion of pneumonia and log input amount.ResultsAmong 568 patients, 438 received invasive MV. XGB achieved an AUROC of 0.839 (95% CI, 0.796–0.883) in the development set and 0.720 (95% CI, 0.637–0.801) in the validation set; repeated nested cross-validation yielded 0.713 (95% CI, 0.665–0.757). The all-MV benchmark had a specificity of 0 and 0.500 balanced accuracy, whereas XGB achieved 0.700 and 0.659, respectively. Excluding pneumonia and log input amount reduced the nested-CV AUROC to 0.654 (95% CI, 0.595–0.703). SHAP analysis identified pneumonia, hematocrit, INR, weight, heart failure, log input amount, and glucose as the highest-importance features.ConclusionThis study developed four machine learning models to assess the necessity of mechanical ventilation support in patients with embolic cerebral infarction and compared their performance. XGB showed the most favorable overall validation profile but requires time-stamped external validation before clinical use.
BackgroundTo systematically evaluate the effects of acupuncture in improving cardiac function and the reported adverse events in patients after percutaneous coronary intervention (PCI) through meta-analysis.MethodsElectronic databases including PubMed, China National Knowledge Infrastructure, Wanfang Medical, China Biomedical Literature Database, VIP Database, Embase, Ovid Medline, Sinomed Database and the Cochrane Library were searched from inception to May 2026. Two reviewers independently screened the literature according to the inclusion and exclusion criteria and extracted data. The methodological quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1), and meta-analysis was performed with Review Manager 5.3. The evidence was appraised per the GRADE framework.ResultsA total of 8 RCTs involving 759 patients were included, with 379 patients in the acupuncture group (247 males and 132 females) and 380 in the control group (conventional treatment or sham acupuncture; 257 males and 123 females). The results of the meta-analysis showed that, revealing that acupuncture was associated with better outcomes than conventional treatment or sham acupuncture in several measures. Specifically, the intervention led to a substantial boost in left ventricular ejection fraction (LVEF) by an average of 4.26 percentage points [95% CI (1.21, 7.31), P = 0.006], while also enhancing functional capacity as evidenced by a 43.88-m improvement in the 6-minute walk distance [95% CI (10.40, 77.36), P = 0.01]. On the biochemical front, acupuncture demonstrated its efficacy by reducing serum creatine kinase-MB (CK-MB) levels [SMD = −1.99, 95% CI (−3.46, −0.52), P = 0.008]. The treatment also showed favorable effects on cardiac remodeling, evidenced by decreased left ventricular end-systolic diameter (LVESD) by 2.56 mm [95% CI (−4.65, −0.46), P = 0.02] and left ventricular end-diastolic diameter (LVEDD) by 1.36 mm [95% CI (−2.34, −0.37), P = 0.007]. Additionally, acupuncture was associated with a lower risk of major adverse cardiovascular events (MACE) by 60% [RR = 0.40, 95% CI (0.24, 0.66), P = 0.0005], positioning it as a promising adjunctive therapy for cardiovascular management.ConclusionCurrent evidence suggests that acupuncture may improve cardiac function in patients after PCI. However, the available literature is limited in both quantity and methodological quality. More rigorously designed, large-sample, high-quality RCTs are warranted to further validate these findings and provide more robust evidence for evidence-based practice.Systematic Review Registrationidentifier CRD420261410954.
BackgroundThe systemic impact of dementia on musculoskeletal health remains poorly characterized. We investigated associations of algorithmically ascertained dementia status with bone fragility, functional trajectories, and low grip strength-defined probable sarcopenia, and explored candidate circulating proteomic indirect-effect signals for these associations.MethodsIn a prospective UK Biobank cohort of 151,751 participants (median follow-up 15.1 years), dementia status was defined from algorithmically derived diagnosis records spanning linked follow-up. Descriptive fixed group-status models evaluated associations with incident osteoporosis and fracture, longitudinal grip-strength and physical-activity trajectories, and baseline probable sarcopenia and probable osteosarcopenia proxy. A time-updated Cox analysis assigned person-time before and on the recorded diagnosis date to the reference state and person-time strictly after that date to the exposed state. In a proteomic subcohort (n = 16,652; Olink Explore 3,072), two-stage screening of 2,923 proteins identified candidate protein signals; these were then evaluated using exploratory, model-based indirect-effect analyses with bootstrap resampling.ResultsIn time-updated models, all-cause dementia after diagnosis was associated with osteoporosis (HR = 1.78, 95% CI 1.43–2.20) and fracture (HR = 3.68, 95% CI 2.34–5.77), with estimates strongest within 0–2 years after diagnosis and attenuated thereafter. For descriptive context, fixed group-status analyses of recorded dementia ascertainment status showed associations with osteoporosis (HR = 2.31, 95% CI 2.06–2.59) and fracture (HR = 3.13, 95% CI 2.27–4.31), accelerated grip decline (β = −0.317 kg/year, p = 1.3 × 10−5), and higher baseline odds of probable sarcopenia (OR = 1.41, 95% CI 1.23–1.61). Under the prespecified observed-sample criteria, EGFR (proportion mediated [PM] = 8.7%), EBI3/IL27 (PM = 5.9%), and CKB (PM = 3.8%) had modest indirect-effect estimates. Across the age-adjusted first-stage screen and the 500-resample full-pipeline bootstrap, EGFR and EBI3/IL27 were the most consistently supported signals; CKB showed lower joint selection stability and was classified as exploratory.ConclusionIn the UK Biobank, algorithmically ascertained dementia status was associated with bone fragility, functional trajectories, and baseline probable sarcopenia-related phenotypes. Time-updated analyses supported elevated postdiagnosis bone risks, with the strongest estimates near the time of diagnosis. EGFR and EBI3/IL27 were the most consistently supported candidate circulating indirect-effect signals for the recorded dementia status–probable sarcopenia association. CKB met the prespecified observed-sample criteria but showed lower selection stability and was retained as exploratory; individual proportions mediated were modest.
BackgroundAntineutrophil cytoplasmic antibody (ANCA) positivity is not uncommon in patients with systemic lupus erythematosus (SLE), however, the diagnosis of concurrent SLE and ANCA-associated vasculitis (AAV) is challenging because SLE tends to mask the clinical manifestations of AAV. Since the kidney is the most frequently affected organ in AAV, we consider that SLE patients with concurrent renal biopsy-proven AAGN warrant the greatest clinical attention.MethodsWe enrolled two patients with newly diagnosed SLE and renal biopsy-proven AAV glomerulonephritis (AAGN). After a literature search, another 57 similar patients were identified. Then the clinical characteristics of these patients were analyzed.ResultsIncluding the two newly reported patients, a total of 51 female and 8 male patients were included. Compared with patients with AAGN alone, patients with combined lupus nephritis (LN) and AAGN had higher SLEDAI scores [14.00 (10.00–18.00) vs. 5.00 (2.50–12.50), P = 0.028], and the 24-h urinary protein level tended to be higher in the LN + AAGN group [3.10 (1.70, 6.69) g/d vs. 1.66 (0.88, 2.15) g/d, p = 0.066]. Patients with elevated C-reactive protein (CRP) levels had lower SLEDAI scores (P = 0.021), higher leukocyte counts (P = 0.005). Patients with elevated leukocyte counts had the lowest proteinuria levels (P = 0.029) but the highest incidence of pulmonary hemorrhage (P = 0.016) compared to those with normal or decreased counts. Low complement 4 and high proteinuria levels were associated with high SLEDAI scores (P = 0.041 and P = 0.027, respectively). Patients who progressed to end-stage renal disease had a higher mortality than those who achieved renal remission (P < 0.001). Renal prognosis did not differ between LN + AAGN and AAGN alone groups (23.1% vs. 25.0%, p = 1.000). The mortality rate was 23.1% in the LN + AAGN group and 5.0% in the AAGN alone group (P = 0.166).ConclusionFor ANCA-positive SLE patients, renal injury may be caused by LN, LN combined with AAGN, or even isolated AAGN. So renal biopsy plays a crucial role in guiding the accurate choice of therapeutic strategy. Further studies are required owing to the heterogeneity of case sources.
ObjectiveTo systematically synthesize the available evidence regarding the effects of rehabilitation interventions on upper limb function, pain and activity performance in patients with systemic sclerosis (SSc), and to further evaluate the limitations of current evidence base and the comparative effectiveness of rehabilitation delivery modes.MethodsComputer searches of databases such as PubMed, Embase, Web of Science, The Cochrane Library, Medline, CINAHL, the SinoMed (China Biomedical Literature Service System), CNKI, WanFang Data Knowledge Service Platform,and VIP were conducted to collect randomized controlled trials on rehabilitation interventions for upper limb function in patients with systemic sclerosis, with search time spanning from database inception (January 1, 1990) to May 2026. Considering the limited number, high clinical heterogeneity and generally moderate-to-high methodological bias risk of included trials, this study adopted a combination of meta-analysis and cautious narrative synthesis. Two researchers independently screened the literature and extracted data according to inclusion and exclusion criteria, and assessed the quality of included studies using the bias risk assessment tool recommended in the Cochrane Handbook 5.1.0. Meta-analysis was performed using RevMan 5.4 software for outcomes with acceptable heterogeneity.ResultsA total of 8 studies were included, with a total of 729 cases. The overall evidence base is limited, with no high-quality low-bias Grade A studies, and a single large trial dominates the pooled weight of many analyses. Meta-analysis results showed that patients with systemic sclerosis who received rehabilitation intervention demonstrated significant improvements in pain [MD = −4.41, 95% CI (−6.54, −2.29), P < 0.0001], hand mobility [MD = −2.58, 95% CI (−4.09, −1.06), P = 0.0009], and DASH score [MD = −6.91, 95% CI (−12.54, −1.27), P = 0.02] at the end of intervention compared to the control group, with statistically significant differences. For outcome indicators that could be subjected to subgroup analysis, the results showed that face-to-face rehabilitation guidance yielded a marginally significant improvement in hand function [SMD = −0.40, 95% CI (−0.77, −0.02), P = 0.04]; however, such subgroup findings should be interpreted cautiously due to small sample size and confounding factors. Meanwhile, the effect of rehabilitation exercises on improving patients' SHAQ scores was not significant [MD = −0.03, 95% CI (−0.25, 0.20), P = 0.81], with no statistically significant difference.ConclusionRehabilitation interventions have a positive effect on the hand function, hand mobility, and local upper limb function of patients with systemic sclerosis, and can also aid in pain relief. However, rehabilitation cannot improve the multidimensional overall disease status reflected by SHAQ. Current evidence is limited by small trial quantity, high heterogeneity and suboptimal methodological quality; firm definitive conclusions and practice-changing recommendations cannot be drawn. Face-to-face rehabilitation displays only preliminary favorable signals compared with remote rehabilitation, and definite superiority cannot be verified. In clinical practice, rehabilitation programs may be selected based on individual patient circumstances with very cautious reference to the limited evidence base.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=1019908, PROSPERO CRD420251019908.
BackgroundTo investigate the effects of different resting intervals on successive intraocular pressure (IOP) and biomechanically corrected IOP (bIOP) measurements from corneal visualization Scheimpflug technology tonometry (CST).MethodsThis was a prospective repeated-measures observational study in young healthy myopes. Three successive IOP and bIOP measurements were acquired using the CST in both eyes of each participant, using four intervals between three successive measurements in the following order, 5 min (T5), 2 min (T2), 30 s (T30), and immediately after the other (Ti). T5-1 was the baseline measurement followed by T5-2 5 minlater, and T5-3 after another 5-min interval. A similar approach was applied to other intervals. A 5-min resting period was provided between successive sets of triplicate measurements. IOP and bIOP results were compared with four intervals and three measurements as the main effects.ResultsA total of 88 myopic participants were recruited. Their mean age was 21.5 ± 2.5 years (from 19 to 31 years). There were 68 right eyes and 20 left eyes, with a spherical equivalent of −4.49 ± 2.39 D (from −9.88 to −0.50 D). A generalized linear mixed model showed that the order of interval did not show significant effect on IOP (p = 0.404), nor the measurement interval (p = 0.074). For bIOP, interval did not show significant effect (p = 0.325) whereas difference in measurement interval, and the effect of successive measurement approached statistical significance (p = 0.054). There was a decreasing trend of bIOP when measurement intervals were 2 min (Friedman test, p < 0.001) and 30 s (Friedman test, p = 0.035). The difference was less than 1 mmHg.ConclusionBoth IOP and bIOP obtained from CST were stable across successive measurement. Although bIOP decreased slightly with 2-min and 30-s, the reduction was small and not clinically significant.
IntroductionRoutine blood tests are often combined into composite indices meant to summarize nutritional, inflammatory, or metabolic status in a single value. Whether these indices reflect the broad syndrome burden seen in geriatric outpatients is unclear, since most of the supporting evidence comes from oncological or surgical cohorts.MethodsWe reviewed the records of 289 patients seen consecutively at a geriatric outpatient clinic over an approximately one-year period and calculated thirteen indices from the first available laboratory panel. The outcome was multisyndrome burden, scored across ten geriatric syndromes, with a burden of four or more defined as high. Each index was entered into a separate logistic regression adjusted for age, sex, comorbidity, and polypharmacy, and the thirteen p-values were corrected for multiple testing with the Benjamini–Hochberg procedure.ResultsOnly the Prognostic Nutritional Index (PNI) and the HALP score remained associated with high burden after correction (adjusted odds ratio per standard deviation 0.55 and 0.64, respectively); none of the inflammatory or metabolic indices reached significance in the full cohort, although the neutrophil-to-lymphocyte ratio and the systemic immune-inflammation index did so in the subgroup in whom all ten components were assessed. Removing the two activity-of-daily-living measures from the outcome left neither association significant, which places the relationship mainly on functional status rather than on an independent inflammatory pathway. Neither index discriminated better than serum albumin measured alone (PNI, area under the curve 0.679 vs. 0.677, DeLong p = 0.90; HALP, 0.654 vs. 0.677, p = 0.52).DiscussionTaken together, the results argue against treating composite laboratory indices as independent markers of geriatric vulnerability: their apparent value largely reflects the albumin and functional components already captured in routine assessment. A low PNI or HALP may still draw attention to a patient who warrants closer functional evaluation, but should not replace direct geriatric assessment.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss, and no established treatment restores impaired motor function. In mouse models of ALS, bone marrow mononuclear cell (BM-MNC) injection improved motor function. In patients with ALS, direct spinal cord injection of BM-MNCs has also been reported to improve motor function. Here, we report the case of a 52-year-old male patient with ALS who underwent intravenous autologous BM-MNC transplantation and demonstrated improved motor function. His revised ALS Functional Rating Scale score increased from 17 before treatment to 18 at 24 weeks after transplantation. The score of Manual Muscle Testing of fifth finger metacarpophalangeal joint flexion improved from 0 before treatment to 2(-) at 24 weeks after transplantation. No serious adverse events were observed. As this is a single case report, additional case series and subsequent randomized clinical trials are essential to clarify the effect of BM-MNC transplantation on ALS outcomes. This case suggests, however, that motor dysfunction in patients with ALS might be reversible. These findings encourage future studies investigating motor function improvement, rather than disease progression slowing, by elucidating the mechanisms underlying BM-MNC transplantation and optimizing treatment.
IntroductionLung cancer is one of the most prominent causes of cancer-related death worldwide, primarily driven by apoptosis resistance linked to the overexpression of antiapoptotic proteins. BCL-XL plays a regulatory function in cellular apoptosis, making it a critical therapeutic target in cancer treatment. In this study, we explored the potential therapeutic effects of phytocompounds isolated from leaves of Ailanthus excelsa to inhibit BCL-XL using an integrated approach combining in silico and in vitro methods.MethodsPhytochemical analysis of the chloroform extract of A. excelsa leaves was performed via gas chromatography-mass spectrometry (GC-MS). Compounds were selected based on their favorable pharmacokinetic properties and subjected to molecular docking against BCL-XL, followed by molecular dynamics simulations over 100 ns, analysis of the simulation trajectory RMSF, principal component analysis, and free-energy landscape. In vitro cytotoxicity of the leaf extract was assessed by MTT assay on lung cancer cell lines.ResultsGC-MS identified 32 major bioactive compounds. Among these, decane,1,9-bis[(trimethylsilyl)oxy] and squalene were selected based on their favorable pharmacokinetic properties. Molecular docking studies revealed that both these compounds interact with the BH3-binding groove of BCL-XL through hydrophobic interactions. Further molecular dynamics simulations of decane,1,9-bis[(trimethylsilyl)oxy] and squalene over 100 ns confirmed the stability and compactness of the protein-ligand complex. The results of the simulation trajectory RMSF indicated stable structural conformations and minor fluctuations around the BH3 domain, suggesting effective binding. Principal component analysis and free-energy landscape exhibited that the binding of squalene promotes multiple conformational states, while decane,1,9-bis[(trimethylsilyl)oxy] limits flexibility in the protein conformations. In addition, the MTT assay conducted on lung cancer cell lines showed significant cytotoxicity of the A. excelsa leaf extract in a dose-dependent manner, highlighting its anticancer properties.DiscussionThis study emphasizes the therapeutic potential of phytocompounds as natural inhibitors of BCL-XL. The integration of GC-MS profiling, molecular docking, molecular dynamics simulations, and in vitro studies provides a comprehensive strategy for the identification of plant-derived lead molecules targeting critical cancer pathways. Further in vivo investigations and molecular validations would provide better insights into BCL-XL-targeted Phyto-therapeutics for lung cancer.
