Cerebral Palsy (CP) is the main cause of motor disabilities in childhood, necessitating innovative approaches to rehabilitation and assistive technology (AT). Simultaneously, artificial intelligence (AI) is increasingly being integrated into devices to create more adaptive, personalized, and effective AT. This systematic review aimed to evaluate the effectiveness and usability of AI-powered assistive technologies designed to support daily activities and rehabilitation in children with CP. Five databases, including Scopus, Web of Science, PubMed, Embase, and IEEE Xplore, were systematically searched, and 23 articles were included in the final analysis. Articles were identified, selected, and categorized into emerging thematic areas based on the primary function and application of the technology. Five key thematic topics were identified: 1) AI-driven motor rehabilitation and gait training for functional mobility; 2) intelligent assessment and monitoring systems for clinical decision support; 3) AI-supported communication, social interaction, and intention recognition tools; 4) gamified and virtual reality-based interventions to enhance engagement and usability; and 5) smart assistive systems supporting daily living and independent mobility. The findings demonstrate a strong trend toward the application of AI technologies in personalized, engaging, and data-driven interventions for children with CP. However, the field is predominantly in the proof-of-concept stage, with limitations including small sample sizes, lack of long-term clinical validation, challenges in user-centered design, and usability for children with CP. AI-powered assistive technologies hold significant potential for transforming the care of children with CP by enabling highly personalized and engaging interventions. To actualize this potential, future work must realize that practical application remains challenging owing to limited clinical validation, technological integration, and usability barriers for children with CP. Future research must prioritize user-centered design and multidisciplinary collaboration to ensure that AI and robotic advancements improve the usability and quality of life for children with CP. This is a systematic review of 23 research articles evaluating the effectiveness and usability of artificial intelligence-powered assistive technologies for supporting daily activities in children with cerebral palsy.AI is enabling a new generation of assistive technologies for children with cerebral palsy that are adaptive, personalized, and focused on improving function across daily life activities, from motor rehabilitation and communication to independent mobility.The successful adoption of AI technologies depend on a user-centered, multidisciplinary approach that closely involves children, families, and clinicians to ensure solutions are not only technologically advanced but also practical, engaging, and clinically meaningful.
To evaluate the effectiveness and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors in elderly patients with type 2 diabetes mellitus, with particular focus on renal and cardiovascular outcomes. This retrospective cohort study analyzed data from 9,915 diabetic patients aged ≥65 years who received antihyperglycemic therapy at Changhua Christian Hospital, Taiwan, between January 2021 and September 2023. Patients were categorized as SGLT2 inhibitor users (n = 3,345) or non-users (n = 6,570). After 1:1 propensity score matching, 1,529 patients remained in each group. Primary outcomes included renal function (measured by eGFR decline), coronary artery disease, ischemic stroke, and heart failure. Secondary outcomes included urinary tract infection, genital infection, diabetic ketoacidosis, and hypoglycemia. SGLT2 inhibitor use was associated with significant renoprotective effects, demonstrated by reduced risk of 30% eGFR decline (HR 0.69, 95% CI 0.59-0.80, p < 0.001) and 50% eGFR decline (HR 0.60, 95% CI 0.45-0.80, p < 0.001). Subgroup analyses revealed that renoprotective effects were more pronounced in patients with higher baseline eGFR (≥50 mL/min/1.73 m2), suggesting greater benefit with early initiation of SGLT2 inhibitors for kidney protection. However, SGLT2 inhibitor use was associated with an increased risk of genital infections (HR 4.29, 95% CI 1.02-18.04, p = 0.047) in patients without prior history of such infections. In elderly patients with type 2 diabetes, SGLT2 inhibitors demonstrate significant renal protective effects, particularly among those with preserved renal function (eGFR ≥50 mL/min/1.73 m2). These findings highlight the importance of considering patient characteristics when evaluating potential benefits of SGLT2 inhibitor therapy. The differential risk patterns suggest that clinicians should consider individual patient profiles and medical histories when prescribing these medications. The occurrence of major adverse cardiovascular events (MACE) did not exhibit a statistically significant difference between the cohort administered SGLT2 inhibitors and the cohort not receiving SGLT2 inhibitors (log-rank p-value = 0.160). Conversely, the recurrence of MACE was markedly reduced in the cohort receiving SGLT2 inhibitors (log-rank p-value < 0.001). These findings should be interpreted in the context of a single-center retrospective design and the inherent limitations of propensity-score-matched observational analyses.
The appearance of disease‑specific autoantibodies (Aab) is a hallmark of celiac disease (CeD). The recent adaption of a no‑biopsy approach places greater reliance on Aab testing. Despite their widespread use, conventional assay formats such as enzyme-linked immunosorbent assays (ELISA) continue to exhibit inherent methodological deficiencies that cannot be readily mitigated. Radio-binding assays (RBA) have historically defined the benchmark for assay performance, but the requirement for radiolabeled reagents and dedicated facilities renders this strategy an untenable solution beyond a limited number of specialized laboratories. This review aims to outline the future role of Aab in the diagnostic algorithm of CeD and to highlight the next-generation techniques that could replace the conventional testing methods. We discuss the diagnostic utility of ELISA, RBA, Electrochemiluminescence assay (ECL), luciferase immunoprecipitation systems (LIPS), antibody detection by agglutination polymerase chain reaction (ADAP) and dissociation enhanced lanthanide fluorescence immunoassay (DELFIA) techniques with emphasis on measuring anti-Transglutaminase 2 (TG2) Aab in the diagnosis of CeD. With the advantages of automation and multiplexing, the new generation of Aab testing modalities like ECL and ADAP may demonstrate sufficient sensitivity and accuracy to warrant inclusion in future CeD diagnostic guidelines. While multiplexing allows the inclusion of multiple Aabs testing from small volumes of blood in an automated manner, this generation of immunoassays are well suited for large-scale screenings and may replace the conventional ELISA and RBA techniques in the near future. Conventional Aab testing with different ELISA kits or RBAs used in specialized laboratories handling radioactivity are still widely being used as clinical diagnostics or in research settings. The analytical performance is still affected by accessibility of limited automation, inter-assay and platform variability, and lack of assay harmonization, emphasizing the need for further technological improvement.With the advantage of automation, multiplexing, and low-volume serum requirements, the new generation of Aab assays such as ECL, DELFIA and ADAP may hold potential for CeD diagnostics and monitoring.The recommendation is to use automated and multiplex platforms for the initial screening of large populations, followed by confirmatory testing in individuals who are Aab positive on screening, using a different modality to confirm results and accurately determine Aab levels.
Sleep disorders-including sleep deprivation, obstructive sleep apnea (OSA), and circadian rhythm disruption-and metabolic diseases such as obesity and type 2 diabetes represent major, interconnected public health challenges. This review aims to synthesize current evidence on the bidirectional crosstalk between these conditions, with a focus on the mediating role of dysregulated adipokine secretion. We elaborate a mechanistic framework wherein specific sleep disturbances disrupt circadian rhythms and alter the secretory profiles of key adipokines, including leptin, adiponectin, interleukin-6 (IL-6), and angiopoietin-like protein 4 (ANGPTL4). Sleep deprivation and fragmentation promote a state of leptin dysregulation and reduce adiponectin levels, while OSA-driven intermittent hypoxia potently upregulates IL-6 and ANGPTL4. These alterations collectively contribute to insulin resistance, dyslipidemia, and chronic low-grade inflammation, thereby elevating metabolic disease risk. Conversely, obesity and diabetes exacerbate sleep disorders through pathways involving visceral adiposity, neuroendocrine dysfunction (e.g. HPA-axis activation), and diabetes-related symptoms (e.g. nocturia, neuropathic pain), forming a vicious cycle. Clinical and preclinical evidence underscores that the synchronization of sleep-circadian biology is fundamental to maintaining adipokine homeostasis and metabolic health. The evidence positions sleep and circadian health as critical, modifiable determinants of metabolic risk. Integrating sleep assessment and evidence-based interventions (e.g. CPAP for OSA, sleep extension, circadian realignment) into standard preventive and clinical frameworks for metabolic diseases is a promising strategy. Public health initiatives should elevate 'quality sleep' as a pillar of health alongside nutrition and physical activity to mitigate the intertwined epidemics of metabolic and sleep disorders. Sleep disorders and metabolic diseases engage in a vicious cycle mediated by the dysregulation of key adipokines (leptin, adiponectin, IL-6, and ANGPTL4), which disrupts circadian rhythms and promotes insulin resistance, inflammation, and dyslipidemia.Adipokine profiling offers a novel mechanistic framework for understanding metabolic risk and serves as a potential early biomarker for individuals with sleep disturbances such as insomnia and obstructive sleep apnea.Integrating sleep assessment and targeted interventions into routine metabolic care represents a promising and cost-effective public health strategy to break this cycle and reduce the global burden of obesity and type 2 diabetes.
Emergence agitation (EA) is a clinically significant complication during early recovery from general anesthesia. This protocol describes a randomized controlled trial designed to determine whether intraoperative low-dose remimazolam maintenance reduces the incidence of EA without prolonging emergence time in patients undergoing oral surgery. This multicenter, randomized, controlled clinical trial will enroll 388 patients scheduled for oral surgery under general anesthesia. Patients will be randomly allocated in a 1:1 ratio to either the remimazolam group, receiving a low-dose intraoperative infusion of remimazolam, or the control group, receiving an equivalent volume of normal saline. The primary outcome is the incidence of emergence agitation; the key secondary outcome is emergence time. Emergence time will be evaluated within a non-inferiority framework, whereas the incidence of emergence agitation will be tested for superiority. Additional endpoints comprise pain scores, analgesic use, the rate of postoperative nausea and vomiting (PONV), recourse to rescue antiemetics, the occurrence of postoperative sleep disturbance (PSD), time spent in the post-anesthesia care unit (PACU), postoperative hospital length of stay, overall recovery quality, the frequency of perioperative adverse events, and patient satisfaction. This trial will investigate the efficacy and safety of intraoperative low-dose remimazolam maintenance in patients undergoing oral surgery. The findings may provide evidence supporting a practical pharmacological intervention to reduce EA and enhance postoperative recovery. Chinese Clinical Trial Registry (ChiCTR2600116544).
Anti-complex nucleosomal remodelling histone deacetylase (Mi2)-positive dermatomyositis (DM) is characterized by severe muscle damage. This study investigated muscle magnetic resonance imaging (MRI) features in anti-Mi2-positive DM, compared them with other DM subtypes, and evaluated their associations with clinical features. DM patients who underwent thigh MRI were enrolled, including 20 anti-Mi2-positive, 20 anti-TIF1γ-positive, 15 anti-NXP2-positive, and 19 anti-MDA5-positive cases. Clinical and imaging data were collected and compared across subtypes. The relationship between MRI features and clinical characteristics was analysed in the anti-Mi2-positive subgroup. Among the four subtypes, anti-Mi2-positive DM had the highest myofascial oedema frequency in the sartorius and the lowest in the biceps femoris (both p < 0.05). All anti-Mi2-positive patients had muscle oedema - most severe in the quadriceps femoris with relative sparing of the semimembranosus and biceps femoris - and the highest total muscle oedema scores (p < 0.001). Eleven (55%) patients had fatty infiltration, predominantly in the gluteus maximus and hamstrings with sparing of the rectus femoris and adductor longus. In this subgroup, treatment-naïve patients had a higher prevalence of diffuse distribution than treatment-experienced (p = 0.042). Compared with anti-TIF1γ-positive patients, the anti-Mi2-positive subgroup had lower total fatty infiltration scores and milder gluteus maximus, adductor longus, and hamstrings involvement (all p < 0.05). In anti-Mi2-positive DM, total muscle oedema scores correlated negatively with Manual Muscle Testing-8 scores and positively with serum creatine kinase levels (both p < 0.05). Preliminary observations in six anti-Mi2-positive patients followed longitudinally showed that muscle oedema decreased after treatment, resolved during remission, and recurred with relapse. This study delineated baseline thigh MRI patterns in anti-Mi2-positive DM and demonstrated that baseline muscle oedema severity correlated with serological and clinical indicators of muscle damage. Additionally, findings from a small longitudinal cohort suggested a potential role for thigh MRI in assessing and monitoring muscle disease activity in this subtype, although these results are preliminary and require validation in larger studies. Our findings identified baseline patterns of oedema and fatty infiltration on thigh muscle MRI in patients with anti-Mi2-positive DM, with oedema being more pronounced and asymmetric than fatty infiltration.Among the four subtypes, anti-Mi2-positive DM showed the highest frequency of myofascial oedema in the sartorius and the lowest in the biceps femoris; it also exhibited the most severe muscle oedema.This study demonstrated that baseline muscle oedema severity correlated with serological and clinical indicators of muscle damage, and findings from a small longitudinal cohort suggested a potential role for thigh MRI in assessing and monitoring muscle disease activity in this subtype, although these results are preliminary and require validation in larger studies.
This study aimed to provide the direct in vivo CT-based visualisation and quantification of local anaesthetic distribution and clearance within the fascial plane following a single-injection serratus anterior plane block (SAPB). A total of 16 participants received an ultrasound-guided SAPB with 40 ml of 0.375% ropivacaine. Computed tomography (CT) scans were performed at 30 and 60 min post-injection. The primary outcome was the clearance rate of ropivacaine from the fascial space between 30 and 60 min. Secondary outcomes included the three-dimensional diffusion range of injectate. CT-based volumetric analysis showed that the volume of the ropivacaine within the fascial plane was 29.1 (28.3, 29.4) ml at 30 min post-injection and decreased to 26.0 (25.2, 26.9) ml at 60 min after a single 40 ml injection of 0.375% ropivacaine, resulting in a clearance rate of 6.4 ± 1.5 ml/h. CT imaging revealed that the injectate was primarily located within the deep serratus anterior plane, showing craniocaudal and anteroposterior spread along the thoracic wall. In the absence of postural restrictions, the injectate exhibited a tendency to migrate caudally over time. This study demonstrates that CT imaging can directly visualise the distribution pattern and quantitatively assess the clearance of local anaesthetic within the fascial plane after a single-injection SAPB.
CD5-positive diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype with poor outcomes. Following the approval of Pola-R-CHP in China, this study aimed to evaluate its efficacy as initial therapy for this high-risk population. We conducted a multicenter, retrospective study of previously untreated CD5-positive DLBCL patients who received Pola-R-CHP as first-line therapy between April 2023 and February 2025. Treatment response was assessed by PET/CT after 3 cycles and at the end of treatment. Among 32 enrolled patients (median age 63.5 years), 78.1% had stage III-IV disease and 59.4% had an International Prognostic Index score ≥3. The overall response rate (ORR) was 100% after 3 cycles, with a complete response rate (CRR) of 71.9%. At end of treatment, the ORR and CRR were 93.8% and 75%, respectively. After a median follow-up of 17.9 months, 2-year progression-free survival (PFS) and overall survival rates (OS) were 70% and 82.7%. After adjusting covariates, failure to achieve a complete response (CR) after 3 cycles was a predictor of inferior survival [PFS HR: 18.1, p = 0.02; OS HR: 12.3, p = 0.033]. Grade 3-4 adverse events occurred in 31.3% of patients, with neutropenia being most common. CD5-positive DLBCL patients exhibited rapid and promising responses to first-line Pola-R-CHP with an acceptable safety profile. Interim response assessment is a potential prognostic factor. In instances where CR is not attained by the interim PET/CT, it is advisable to consider treatment modification, as this may indicate a potential failure to achieve CR.
Myocardial injury in severe community-acquired pneumonia (SCAP) is often under-recognized, and interpretation of high-sensitivity cardiac troponin I (hs-cTnI) may be complicated by renal dysfunction and critical illness. We evaluated whether admission interleukin-8 (IL-8) and soluble suppression of tumorigenicity 2 (sST2) could support early risk stratification of guideline-consistent myocardial injury in patients with SCAP. In this prospective cohort of 146 patients with SCAP, guideline-consistent myocardial injury was defined as hs-cTnI elevation above the assay-specific 99th percentile upper reference limit. Admission IL-8, sST2, and their combination were assessed using receiver operating characteristic curve analysis and 10-fold cross-validation. Fixed and estimated glomerular filtration rate (eGFR)-stratified hs-cTnI thresholds were compared in an exploratory analysis. An exploratory subgroup analysis was performed among patients with CURB-65 ≤ 1. The median age was 71 years; 91 patients (62.3%) were male and 55 (37.7%) were female. Myocardial injury occurred in 88 patients (60.3%). The IL-8 + sST2 model showed good discrimination for myocardial injury, with an AUC of 0.825 (95% CI: 0.751-0.895) and an internally cross-validated AUC of 0.812. Admission IL-8 showed stronger individual discrimination than sST2. eGFR-stratified hs-cTnI thresholds did not reduce discordant hs-cTnI elevations in this cohort, likely because few patients had moderate-to-severe renal dysfunction. Among patients with CURB-65 ≤ 1 (n = 38), IL-8 > 43.53 pg/mL was associated with a higher prevalence of myocardial injury (76.2% vs. 29.4%, p = 0.004). An exploratory 0-2 biomarker score showed a graded increase in myocardial injury prevalence across score categories: 15.4%, 62.5%, and 78.6%. Admission IL-8 was associated with guideline-consistent myocardial injury in patients with SCAP, whereas sST2 showed weaker individual discrimination. The combined model had numerically higher discrimination than IL-8 alone, but the incremental contribution of sST2 remains uncertain. These findings represent an initial evaluation and require external validation before clinical implementation.
The remarkable researches have been made to clarify the pathogenesis of DR, but relatively little is known about it. The goal was to summarize the epidemiology and mechanism of DR, provide screening and biomarker information of DR and suggest the strategies for treatment and intervention of DR. This article synthesizes recent findings on intricate interrelated patho-physiological mechanisms elicited by hyperglycaemia underlie the progression of DR. DR has long been considered a microvascular disorder, but accumulating evidences demonstrate that retinal neurodegeneration like activated microglial is involved as well. The progression of DR is underpinned by complex, interconnected pathophysiological mechanisms triggered by hyperglycaemia, including vascular endothelial growth factor (VEGF), methylglyoxal (MGO), Wnt signalling pathways, retinal neurodegeneration and other factors. Enhanced comprehension of the fundamental pathophysiological mechanisms, coupled with advancements in computer technology, fosters the development of innovative approaches to screening, diagnosis and early intervention for DR. DR, a multifactorial complication of diabetes mellitus, necessitates continued research into precise screening methodologies and targeted therapeutic strategies.
We sought to investigate whether growth hormone (GH) treatment increases the risk of scoliosis in children with short stature and analyse a dose-response relationship. A retrospective cross-sectional and cohort study design was used. The cross-sectional study included 1160 children with short stature (355 and 805 in the GH-exposed and non-exposed groups, respectively). The scoliosis prevalence was compared. A total of 313 short stature children without scoliosis at baseline were enrolled in the cohort study (158 and 155, respectively, in the GH and non-GH groups). The median follow-up time was approximately 4.5 years. The relationship between risk factors and GH dose and the occurrence of scoliosis was evaluated with the outcome of new-onset scoliosis. The incidence of scoliosis in the GH exposure group was significantly higher than that in the non-exposure group (5.40% vs. 2.40%, p=0.008). The risk of scoliosis in the GH group was 2.726 times higher than that in the non-GH group (HR=2.726, 95%CI: 1.326-5.605, p=0.006). The total GH dose was positively correlated with scoliosis risk, and there was a dose-response relationship between the total GH dose and the risk (HR=1.002, 95%CI: 1.001-1.003, p<0.001). A dose-response relationship was confirmed, with the predicted probability of scoliosis increasing continuously with cumulative GH dose. GH therapy is an independent risk factor for scoliosis in children with short stature, with a significant dose-response relationship. The cumulative GH dose can be used as a preliminary reference indicator for risk stratification and personalized monitoring.
Patients undergoing minimally invasive esophagectomy (MIE) frequently experience moderate-to-severe postoperative pain and anxiety-depressive symptoms, compromising postoperative quality of recovery (QoR). Esketamine is a promising adjunct for analgesia and anxiolysis; however, the effect of low-dose esketamine on patient-centered recovery outcomes in MIE remains unclear. In this double-blinded, multicenter randomized controlled trial, patients scheduled for elective McKeown esophagectomy were allocated to esketamine (0.25 mg/kg loading dose and 0.125 mg/kg/h continuous infusion during surgery) or placebo (equivalent volume and rate of saline). The primary outcome was the QoR-15 score on postoperative day (POD) 2. Secondary outcomes included QoR-15 scores on POD 1, 3, 7 and 30. Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A) and Depression Subscale (HADS-D) scores, numeric rating scale (NRS) pain scores, and the Brief Pain Inventory (BPI) scores on POD 1 to 3, and safety evaluations. A total of 198 patients were analyzed (esketamine, n = 98; placebo, n = 100). Intraoperative esketamine significantly improved QoR-15 scores on POD 2 (116.9 ± 9.4 vs. 110.2 ± 9.8, p < 0.001) and POD 3 (123.6 ± 7.2 vs. 116.8 ± 8.4, p < 0.001) compared with placebo. HADS-A and HADS-D scores were lower in the esketamine group on POD 1 to 3 (all p < 0.001). Additionally, esketamine recipients reported significantly lower NRS scores at rest and during movement and BPI scores for pain severity and pain interference items (all p < 0.001). There were no significant between-group differences in safety outcomes. Intraoperative low-dose esketamine improved early, patient-reported recovery after MIE by enhancing analgesia and reducing postoperative anxiety and depression without increasing adverse events. Chinese Clinical Trial Register (identifier: ChiCTR2400088916). Patients undergoing minimally invasive esophagectomy often experience poor quality of recovery due to postoperative pain, anxiety, and depression. Effective analgesia and psychological support are essential to improving postoperative recovery in these patients.No prior studies have specifically examined the effect of low-dose esketamine on patient-centered recovery outcomes in patients undergoing minimally invasive esophagectomy.Low-dose esketamine (0.25 mg/kg loading dose and 0.125 mg/kg/h continuous infusion during surgery) improved early, patient-reported recovery after minimally invasive esophagectomy by enhancing analgesia and reducing postoperative anxiety and depression, without increasing adverse events.
Gestational diabetes mellitus (GDM) has a high global prevalence and arises from complex interactions between genetic predisposition and environmental factors. GDM is associated with metabolic disturbances and chronic low-grade inflammation, both of which contribute to its pathogenesis. This study aimed to investigate the association between GDM and 135 single-nucleotide polymorphisms (SNPs) across 20 genes related to metabolic traits. In this case-control study, 152 pregnant women with GDM and 684 pregnant women with normal glucose tolerance (NGT) who underwent antenatal examination at Siriraj Hospital, Bangkok, were enrolled. Clinical data and blood samples were collected from all participants. Genomic DNA was isolated and subjected to whole-genome sequencing using the DNBSEQ-T7RS high-throughput sequencing platform. Genotype analyses were performed using R software, and haplotype analyses were conducted using the online SNPStats software. After adjusting for maternal age and pre-pregnancy body mass index, polymorphisms in TCF7L2 (rs34872471, rs7901695, rs4506565, rs7903146, rs12243326, and rs12255372), NEDD1 (rs10431408, rs11830756, rs249579, rs249585, and rs4762339), CMIP (rs2306115 and rs201681534), CDKAL1 (rs4710942), GCKR (rs2293572 and rs2293571), and GCK (rs5883890) were significantly associated with the risk of GDM. Haplotype analysis demonstrated that the TCF7L2 rs12243326-rs12255372 CA haplotype was associated with a decreased risk of GDM (OR = 0.44, 95% CI: 0.23-0.81), while the NEDD1 rs249579-rs249585-rs4762339 GGT haplotype was associated with an increased risk of GDM (OR = 1.40, 95% CI: 1.08-1.82). These findings suggest that genetic variations in TCF7L2, NEDD1, CMIP, CDKAL1, GCK, and GCKR contribute to GDM susceptibility in the Thai population.
Granulomas can be found in different tissues and are associated with a variety of processes. To understand the primary diagnoses is the aim of this study. We retrospectively described a cohort of patients with a diagnosis of granulomas in histopathological samples over an 11-year period. Demographic characteristics, histopathological pattern and organ involved, diagnostic tests performed (microbiological, radiological and laboratory findings) and final diagnosis were analysed. The principal causes of granulomas were studied according to the organ involved, histopathological characteristics, and the patient's origin. The techniques employed for diagnosis were evaluated. Six hundred twenty-six patients (median [IQR] age, 50 [33-64] years; 52% male) were analysed. Granulomas were non-necrotising in 56% (350) and necrotising in 24% (150) of cases. The main organ affected was gastrointestinal in 25% (157), ganglionic in 23% (142), pulmonary in 11% (71), hepatic in 10% (65) and skin tissue in 7% (44). The main aetiologies were infectious diseases (138; 22%), predominantly mycobacteria, followed by inflammatory bowel disease (IBD) (14%; 85), sarcoidosis (10%; 65), and neoplasms (9%; 56). In Western European patients, IBD was the main diagnosis (17% [78] vs 4% [7]; p < 0.001), whereas in foreign patients, it was tuberculosis (33% [56] vs 9% [41]; p < 0.001). Microbiological culture was performed in only 34% (210) of cases. Infectious diseases were the primary cause of granulomas, followed by inflammatory diseases, sarcoidosis and response to neoplasms. The distribution of aetiologies varies according to the organ affected and the nationality of the patient. The implementation of a structured diagnostic algorithm may facilitate the evaluation and management of patients with granulomatous inflammation.
Minimal residual disease (MRD) is a major cause of postoperative recurrence in colorectal cancer (CRC), significantly impacting survival outcomes. This study aimed to evaluate the methylation status of the SEPTIN9 gene (mS9) in circulating tumor DNA (ctDNA) as a biomarker for detecting MRD and predicting recurrence in post-surgery CRC patients. In this retrospective, single-center analysis, we evaluated mS9 in ctDNA as a biomarker for postoperative recurrence among 68 patients with stage I-IV CRC. The inclusion of stage IV patients is notable, as it substantially affects the overall recurrence risk profile of the cohort. Plasma samples collected after curative resection were analyzed for mS9 via real-time quantitative PCR, and its association with recurrence-free survival (RFS) was retrospectively examined. Postoperative mS9 positivity in ctDNA was significantly associated with reduced RFS. Patients with mS9-positive in ctDNA one month after surgery exhibited markedly shorter RFS than those who were mS9-negative. Additionally, mS9 positivity was correlated with a higher recurrence risk both in early and long-term postoperative stages, demonstrating superior predictive performance to carcinoembryonic antigen (CEA). ctDNA mS9 can serve as an effective non-invasive biomarker for MRD detection and showed stronger recurrence-risk stratification than CEA in this cohort. The combination of mS9 and CEA further enhances prognostic accuracy for CRC patients.
Patients undergoing dialysis are at an elevated risk of cardiovascular events. This study aimed to develop machine learning (ML) prediction models to identify risk factors for major adverse cardiovascular events (MACE) in dialysis patients. This retrospective study included 203 patients undergoing dialysis with a median age of 45.0 years and 64.0% male. The participants were divided into training and test sets in a 7:3 ratio. LASSO regression selected characteristic variables from patients'general information, laboratory tests, and echocardiographic parameters (including global longitudinal strain [GLS]). Eight ML models were constructed,and SHAP analysis evaluated feature importance. The incidence of MACE (including myocardial infarction, unstable angina, heart failure, and cardiovascular death) in dialysis patients was 38.92%. The average follow-up period was 18 months. LASSO regression identified eight feature variables. Among the ML models, AdaBoost demonstrated superior performance, with an AUC of 0.883 (95% CI: 0.830-0.937), accuracy of 0.804, sensitivity of 0.864 and specificity of 0.762 in the training set, and an AUC of 0.809 (95% CI: 0.706-0.912), accuracy of 0.750, sensitivity of 0.90 and specificity of 0.675 in the test set. The SHAP analysis identified N-terminal pro-brain natriuretic peptide (NT-proBNP) level, estimated glomerular filtration rate (eGFR), GLS and age as the four most important features for predicting MACE in patients undergoing dialysis (mean absolute SHAP values: 0.199, 0.176, 0.096 and 0.091, respectively). Elevated NT-proBNP, advanced age, reduced eGFR and impaired GLS were independently associated with an increased risk of MACE in patients undergoing dialysis.
This study aimed to investigate the biomechanical effect of external trunk perturbations on the plant leg during a football instep kick. Fifteen healthy male national level division-II football athletes were recruited as participants. A Vicon three-dimensional motion capture system synchronized with Kistler force plates was utilized to collect kinematic and kinetic data during standardized instep kicking. Joint angles, moments, and stiffness of the plant leg under four perturbation conditions. Two-way repeated measures ANOVA were employed for statistical analysis. Significant main effects of perturbation anticipation and direction on the biomechanical variables of the plant leg were found. UN perturbation increased hip flexion-extension (F = 21.94, p < 0.01) and abduction-adduction (F = 30.64, p < 0.01) and knee abduction-adduction (F = 20.13, p < 0.01) range of motion. Reduced knee extension angles, increased ankle inversion angles, and abnormal changes in knee flexion-extension moments and ankle plantarflexion moments were observed, indicating compromised joint stability. Regarding directional effects, contralateral perturbations (right side) produced more pronounced alterations with increased hip adduction angles (F = 20.75, p < 0.01) and moments, higher peak knee adduction angles (F = 8.8, p = 0.01), and enhanced ankle inversion-eversion stiffness (F = 9.11, p < 0.01). As the key findings suggested, the dynamic stability under UN perturbation should be enhanced to improve the resistance of perturbations and movement control, thereby providing reference for injury prevention and training optimization.
Left ventricular thrombus (LVT) is a significant complication in ischemic cardiomyopathy (ICM). However, factors associated with LVT have mainly been reported in patients with recent myocardial infarction (MI), while data in chronic ICM remain limited. This study aimed to identify factors associated with CMR-detected LVT in patients with chronic ICM (left ventricular ejection fraction [LVEF] < 50% of ischemic etiology, >40 days post-MI), develop a CMR-based risk score, and evaluate the prognostic implications of LVT on major adverse cardiovascular events (MACE). This study included 790 patients with ICM who underwent CMR at an academic hospital in Thailand between 2016 and 2023. Factors associated with LVT were identified using logistic regression analyses. A CMR-based risk score was developed and validated, with discriminative performance assessed by the area under the receiver operating characteristic curve (AUC-ROC). MACE, defined as a composite of cardiovascular death, ischemic stroke, transient ischemic attack, systemic embolism, nonfatal MI, or heart failure hospitalization, was also evaluated. Factors associated with MACE were assessed using Cox regression analysis. The mean age was 66.9 ± 11.3 years, and 75.3% were male. LVT was detected in 116 patients. Independent factors associated with LVT included apical aneurysm, apical late gadolinium enhancement (LGE), and the number of LGE segments. The CMR-LVT Score, incorporating these variables, demonstrated an AUC of 0.73 (95%CI, 0.68-0.77;p < 0.001) in the derivation cohort and 0.79 (95%CI, 0.69-0.90;p < 0.001) in the validation cohort. During a median follow-up of 3.2 years (IQR, 1.6-5.5), 150 MACE occurred. Baseline LVT was independently associated with MACE (adjusted HR 2.38, 95%CI 1.31-4.30;p = 0.004). In patients with ICM undergoing CMR, apical aneurysm, apical LGE, and LGE extent were independently associated with LVT. The CMR-LVT Score demonstrated acceptable discriminative performance for identifying higher-risk patients who may benefit from more intensive follow-up. LVT was also independently associated with MACE.
The coexistence of acute ischemic stroke (AIS) and unruptured intracranial aneurysms (UIAs) is relatively common, but the safety of antithrombotic therapy in this population remains uncertain. This study evaluated whether different secondary prevention regimens influence UIA progression or rupture risk. This single-center retrospective cohort study included patients with AIS and concomitant saccular UIAs between January 2016 and December 2021. Patients were categorized according to long-term antithrombotic exposure: single antiplatelet therapy (SAPT), anticoagulation, or no regular therapy. Dual antiplatelet therapy (DAPT) was analyzed separately. The primary outcome was aneurysm rupture; secondary outcomes included symptomatic events and radiographic progression (≥1 mm growth). Among 197 patients (mean age 68.4 ± 10.2 years; 53.8% female), 140 received SAPT, 36 received anticoagulation, and 21 received no regular therapy. During a mean follow-up of 28.6 ± 18.4 months, aneurysm rupture occurred in two patients (1.0%). No ruptures occurred in the anticoagulation group. Firth's penalized logistic regression showed no significant association between antithrombotic regimen and aneurysm rupture (anticoagulation vs SAPT: OR 0.41, 95% CI 0.01-5.21; no therapy vs SAPT: OR 3.21, 95% CI 0.21-45.6; both p > 0.05). In patients with small incidental saccular UIAs and AIS, standard secondary prevention regimens were not associated with an increased risk of aneurysm rupture. However, the limited number of rupture events and potential residual confounding warrant cautious interpretation. Secondary stroke prevention should remain the priority, with individualized assessment of aneurysm-related risks.
Multiple sclerosis (MS) significantly affects patients' quality of life (QoL), particularly in resource-limited settings. This multicentre study aimed to identify factors influencing QoL among MS patients in Northwest Ethiopia, where data are scarce. A cross-sectional study was conducted from January to June 2024 among 427 MS patients (≥18 years, diagnosed using McDonald criteria) attending three referral hospitals (University of Gondar, Debre Tabor, Felege Hiwot). Stratified sampling ensured representation across disease severity. Sociodemographic, clinical, psychological and behavioural data were collected. QoL was measured using the MSQOL-54 questionnaire. Multiple regression identified predictors of QoL, expressed as β coefficients and p values. Treatment adherence was assessed only among patients receiving disease-modifying therapy (DMT) (n = 310), and this subgroup was used for adherence-related analyses. The mean age of participants was 43 years, and 58.3% were female. Disease severity was classified as mild in 50.4%, moderate in 34.7%, and severe in 15.0% of participants. Low physical and mental QoL were reported in 34.9% and 31.6%, respectively. Lower QoL was significantly associated with greater disease severity (β = -0.85, p = 0.001), illness duration >10 years (β = -0.35, p = 0.002), fatigue (β = -1.10, p < 0.001), anxiety (β = -1.00, p < 0.001), depression (β = -1.20, p < 0.001), cognitive impairment and treatment non-adherence (evaluated only among DMT-treated patients). Moderate-to-high physical activity (β = 0.60, p = 0.001) and strong social support (β = 0.70, p = 0.001) were associated with higher QoL. QoL among MS patients was strongly influenced by disease severity, treatment adherence (among patients receiving DMT), fatigue, psychological distress, cognitive function, physical activity and social support. Interventions targeting these modifiable factors may improve patient outcomes. This study provides important evidence from Ethiopia and helps address a significant knowledge gap regarding MS care in resource-limited settings.