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Wearable Sleep Monitoring in Pediatric Acute Lymphoblastic Leukemia: Associations With Subjective Sleep Ratings and Neurocognitive Functioning.

BACKGROUND: Sleep disturbances are associated with increased fatigue, reduced quality of life, and neurocognitive dysfunction and have emerged as a common complication among pediatric cancer survivors. Sleep disturbances are particularly concerning given their potential to exacerbate existing neurocognitive impacts of cancer treatments. This pilot study examined the feasibility and acceptability of a home-wearable EEG-based sleep device (Sleep ProfilerTM) for acute lymphoblastic leukemia (ALL) survivors as well as associations between specific sleep parameters and neurocognitive functioning. PROCEDURE: Children (ages 8-12; M = 10 years, SD = 1.6; N = 23) >6 months post-treatment for ALL were enrolled at clinical visits and wore the Sleep ProfilerTM for two consecutive nights at home, followed by neurocognitive testing of attention, inhibitory control, working memory, and processing speed. Parents completed subjective measures of child sleep, anxiety, depression, and acceptability. Feasibility reflected the percentage of children wearing the device at least one night and the percentage of nights with good EEG quality data. RESULTS: All participants wore the device both nights, with 84% meeting the threshold for good quality measurement. Few children met recommended quantity and quality sleep thresholds based on objective measurement, including 5 patients with elevated snoring levels; 43.5% of subjective ratings fell above the threshold for sleep disturbance. Greater sleep latency was associated with worse inhibitory control (r = -0.42, p = 0.046), and total sleep time was positively associated with inhibitory control and attention. CONCLUSIONS: Findings confirm the feasibility and acceptability of home EEG sleep monitoring in school-age survivors, and associations of sleep latency and snoring with reduced neurocognitive functioning may offer modifiable risk factors for aspects of neuropsychological dysfunction common in pediatric survivorship. CLINICAL TRIAL REGISTRATION: At the time this study was conducted, we were not required to register the study on ClinicalTrials.gov. It was a single-institution feasibility study without intervention, which was not considered a clinical trial.

Humans

Feasibility and barriers to same-day physical therapy following lumbar fusion surgery.

OBJECTIVE: To evaluate the feasibility of same-day (postoperative day 0; POD0) physical therapy (PT) following lumbar fusion and to identify factors associated with failure to participate. METHODS: This retrospective study analyzed prospectively collected data from patients undergoing single-level posterior spinal fusion (PSF), with or without anterior (ALIF) or lateral (LLIF) interbody fusion, between January and December 2024 at a single institution. A standardized POD0 PT protocol was implemented for eligible patients. Patients were categorized into two groups: successful POD0 PT (ambulatory on POD0) and unable to participate. Demographic and surgical variables were compared between groups. Reasons for inability to participate were recorded and categorized. RESULTS: Among 129 patients in whom POD0 PT was attempted, 84 (65%) successfully participated, while 45 (35%) were unable. There were no significant differences in age, sex, BMI, ASA class, operative time, estimated blood loss, or surgical approach between groups. Patients who successfully completed POD0 PT had a significantly shorter hospital length of stay compared to those who did not (3.4&#xa0;&#xb1;&#xa0;1.6 vs 5.8&#xa0;&#xb1;&#xa0;2.9&#xa0;days, P&#xa0;<&#xa0;0.001), with no differences in complication rates, discharge disposition, emergency department visits, or reoperation rates. The most common barriers to POD0 PT were postoperative pain, medical issues (e.g., orthostatic hypotension, nausea, dizziness), and anesthesia-related somnolence. Less common factors included postoperative restrictions and logistical issues such as brace availability. CONCLUSIONS: POD0 PT following lumbar fusion is feasible in the majority of patients and is associated with a shorter hospital stay without increased complications. Failure to participate was not associated with the baseline patient or surgical characteristics evaluated in this study. Instead, the most common barriers were postoperative pain, transient medical issues, and anesthesia-related somnolence, suggesting that optimization of modifiable perioperative factors may improve the implementation of POD0 PT.

Humans

Comparison of Keverprazan-based versus esomeprazole-based dual therapy for initial treatment of Helicobacter pylori infection: a prospective, multicenter, randomized controlled trial.

BACKGROUND: Keverprazan offers a new perspective for Helicobacter pylori eradication. This study compared 14-day keverprazan-amoxicillin therapy with esomeprazole-amoxicillin therapy to explore a superior treatment strategy. METHODS: This was a prospective, open-label, multicenter, randomized controlled trial in adult patients with treatment-naive H. pylori infection. Participants were randomly assigned to receive either 14-day of KA therapy (Keverprazan 20&#x2009;mg b.i.d plus amoxicillin 1&#x2009;g t.i.d) or 14-day of EA therapy (Esomeprazole 40&#x2009;mg b.i.d plus amoxicillin 1&#x2009;g t.i.d). The primary outcome was the H. pylori eradication rate. Secondary outcomes were the incidence of adverse events and patient adherence. RESULTS: A total of 264 patients were enrolled in the study. In the intention-to-treat (ITT) analysis, the eradication rates for the 14-day KA group and the 14-day EA group were 87.9% and 80.3%, respectively (p&#x2009;=&#x2009;0.092); in the modified intention-to-treat (mITT) analysis, the eradication rates were 92.1% and 86.2%, respectively (p&#x2009;=&#x2009;0.135); and in the per-protocol (PP) analysis, the eradication rates were 93.5% and 88.3%, respectively (p&#x2009;=&#x2009;0.155). Non-inferiority was confirmed between the two groups (all p&#x2009;<&#x2009;0.001). Adverse events and patient adherence were similar between the two groups. CONCLUSION: For treatment-naive H. pylori infection, the 14-day KA therapy is non-inferior to EA therapy. Given its good tolerability, pharmacogenomic independence, and potent acid suppression, KA is a rational first-line alternative to EA in the Chinese population.

Humans

SBUF-SMUF: On the path to the optimum hemofiltration technique in pediatric cardiopulmonary bypass: A randomized clinical trial.

BACKGROUND: Hemofiltration during pediatric cardiopulmonary bypass (CPB) is essential to mitigate hemodilution, inflammatory responses, and postoperative complications. Conventional ultrafiltration (CUF) is widely practiced, but novel methods such as subzero balanced ultrafiltration combined with simple modified ultrafiltration (SBUF-SMUF) may offer superior outcomes. OBJECTIVE: To compare the clinical efficacy and safety of CUF versus SBUF-SMUF in pediatric patients undergoing open-heart surgery. METHODS: In this prospective randomized, outcome-assessor-blinded clinical trial, 80 pediatric patients with congenital heart disease were allocated to either CUF (n = 40) or SBUF-SMUF (n = 40) during CPB. Baseline demographics, intraoperative characteristics, fluid balance, blood product utilization, and postoperative outcomes were assessed. Statistical analysis was conducted using independent t-tests, Chi-square tests, and Fisher's exact tests. Statistical significance was defined as a two-tailed p-Value of less than 0.05. RESULTS: Demographic and preoperative variables were comparable between groups. Mean fluid balance was significantly positive in the CUF group (+192.1 &#xb1; 178.8 mL) but negative in the SBUF-SMUF group (-105.0 &#xb1; 78.9 mL, p < 0.001). The SBUF-SMUF group required significantly less intraoperative PRBC (141.7 &#xb1; 70.2 vs. 261.0 &#xb1; 68.8 mL, p < 0.001) and postoperative FFP transfusion (2% vs. 10%, p = 0.020). Post-bypass hematocrit levels were higher (31.2% vs. 27.3%, p = 0.001) and extubation occurred earlier in the SBUF-SMUF group (1.05 &#xb1; 1.03 vs. 2.27 &#xb1; 2.37 days, p = 0.006). No significant differences were observed in potassium levels or incidence of acute kidney injury. CONCLUSION: The SBUF-SMUF technique is safe, effective, and superior to CUF in optimizing fluid balance, reducing blood product utilization, and facilitating earlier extubation in pediatric cardiac surgery. No additional risk of oliguria or electrolyte imbalance was observed compared to CUF. Its simplicity and reproducibility support its consideration as a standard approach in pediatric CPB.

Humans

Vitamin D Supplementation Modulates Base Excision Repair (BER) Machinery in Systemic Sclerosis: A Prospective Longitudinal Study.

Systemic sclerosis (SSc) is a chronic, autoimmune, fibrotic disorder involving immune dysregulation, vascular abnormalities and progressive fibrosis. Although oxidative stress and defective DNA repair have been implicated in its pathogenesis, the impact of vitamin D on DNA repair pathways remains unclear. This study aimed to investigate the expression of DNA repair enzymes in SSc, explore their relationship with vitamin D status and assess the effects of vitamin D supplementation on the transcriptional expression of these enzymes. Peripheral blood samples were collected from 52 female patients with SSc and 31 age-matched healthy controls (HCs). Gene expression levels of base excision repair (BER) enzymes (APE1 and OGG1) and nucleotide excision repair (NER) enzymes (XPA and XPC) were analyzed. Serum vitamin D levels were measured and correlated with disease activity scores. In a prospective arm of the study, patients received six months of vitamin D supplementation and their DNA repair capacity was evaluated pre- and post-intervention. Baseline expression of APE1 and OGG1 was significantly lower in SSc patients than in HCs, whereas expression of the NER genes remained unchanged, indicating selective impairment of the BER pathway. Vitamin D deficiency was prevalent in SSc and inversely correlated with disease severity. Supplementation significantly increased serum vitamin D levels and up-regulated APE1 and OGG1 expression; while NER genes remained unaffected. These findings are consistent with evidence of elevated oxidative DNA lesions in SSc and support a mechanistic link between BER activity and the repair of oxidative DNA damage. SSc patients exhibit reduced transcription of BER-specific enzymes associated with vitamin D deficiency andrestoration of vitamin D levels partially rescues BER enzyme expression. These findingshighlight a potentially modifiable axis linking micronutrient status, genomic stability and disease activity and provide a rationale for investigating vitamin D optimization as an adjunctive strategy to enhance DNA repair and potentially attenuate inflammatory and fibrotic processes in SSc.

Humans

Effectiveness of passive vs. assistive robotic gait training on functional recovery and neuroplasticity post-stroke: A randomized controlled trial.

OBJECTIVE: This study seeks to compare the impacts of various robotic gait training (RAGT) modes on lower limb motor function recovery in stroke patients while exploring the corresponding neural mechanisms. DESIGN: A single-blind, randomized controlled trial. SETTING: Inpatient Rehabilitation Facility. PARTICIPANTS: Forty-eight patients aged 18-80 who had experienced their first unilateral subacute stroke accompanied by walking impairments were included. INTERVENTIONS: Participants were randomly assigned to: (1) assistive mode training, (2) passive mode training, or (3) control group receiving only traditional rehabilitation. Clinical and neurological outcomes were assessed at pre-intervention (T0), and post-2-week intervention (T1). MAIN OUTCOME MEASURES: Outcomes were evaluated using the Fugl-Meyer Assessment for Lower Extremity, Berg Balance Scale, Modified Barthel Index, the Functional Ambulatory Category, and functional near-infrared spectroscopy. RESULTS: Among the 48 patients recruited, significant time effects were observed across all groups in FMA-LE scores (p&#x202f;<&#x202f;0.001). Notable improvements were detected in the conventional group (MD = 2.69, p&#xff1c;0.01) and the passive group (MD = 3.67, p&#x202f;<&#x202f;0.001), with the assistive mode also demonstrating a significant effect (MD = 1.79, p&#x202f;<&#x202f;0.05). BBS scores improved across all groups; however, no significant differences were noted between the groups (p&#x202f;=&#x202f;0.11). Similarly, MBI scores showed a significant time effect (p&#x202f;<&#x202f;0.001), without notable group differences (p&#x202f;=&#x202f;0.29). CONCLUSION: All training modalities effectively enhanced motor function, balance, and daily living skills in stroke patients. Distinct cortical activation and connectivity patterns were observed between training modalities, which may reflect different neuroplastic mechanisms. These preliminary neural differences may help inform personalized rehabilitation strategies, although no clinical superiority of one mode over another can be concluded from the present data.

Humans

Ageing effects on chemical, physical, mechanical, and morphological properties of clear aligners - a systematic review.

BACKGROUND: Clear aligner (CA) therapy has experienced rapid use over the past two decades to treat orthodontic malocclusions. However, evidence on CA material degradation in the oral environment remains limited and often focuses on single brands or isolated material properties. OBJECTIVES: To investigate CA ageing characteristics across different materials and brands and evaluate the chemical, physical, mechanical, and morphological changes following simulated or intraoral ageing. SEARCH METHODS: Five databases (PubMed, Web of Science, MEDLINE [Ovid], ProQuest, and Scopus) were searched to 18 March 2026, with no restrictions. ELIGIBILITY CRITERIA: Studies assessing CA properties after intraoral use or simulated ageing (thermocycling, cyclic loading, or liquid immersion) were included. DATA COLLECTION AND ANALYSIS: Study selection followed PRISMA 2020. RoB was assessed using QUIN for purely in vitro studies, JBI for cohort in vivo studies, and Cochrane RoB 2 for RCTs. Results were synthesised narratively and organised by property domain, as substantial methodological heterogeneity precluded formal meta-analysis. Where protocols were comparable, a simple pooled weighted mean was calculated and presented graphically. RESULTS: Ninety-five studies were included. RoB was low in eight studies, moderate in sixty-two, and high in twenty-five. Chemical composition remained largely stable during ageing, though some brands showed trace elemental release. Physical, mechanical, and morphological properties showed material-dependent deterioration. Pooled discolouration was greatest with coffee (weighted mean &#x394;E&#x2009;=&#x2009;70.9), versus tea (&#x394;E&#x2009;=&#x2009;18.4) and red wine (&#x394;E&#x2009;=&#x2009;11.5), with Invisalign&#xae; consistently exceeding the clinically perceptible threshold. Force decay of 40-90% typically occurred within 48&#xa0;h. Thermoplastic polyurethane (TPU)-based and directly printed aligners (DPAs) generally showed greater susceptibility than polyethylene terephthalate glycol-modified (PETG)-based aligners, though findings on hardness, roughness, and stiffness were inconsistent. CONCLUSIONS: CA materials undergo clinically relevant degradation during use, particularly in TPU-based and DPAs aligners. Clinicians may need to prioritise material-specific protocols, reinforce dietary and cleaning instructions, and consider force decay when determining aligner replacement intervals. PROSPERO number: CRD420251110248.

Humans

MIS-TLIF Versus Open TLIF in Combined Lumbar Stenosis and Low-Grade Spondylolisthesis : Of Discharge Timing and Treatment Pricing.

STUDY DESIGN: An open-label, randomized, noninferiority clinical trial. OBJECTIVE: To determine the effectiveness of the MIS-TLIF over the O-TLIF in patients with symptomatic lumbar stenosis combined with low-grade spondylolisthesis by comparing the clinical efficacy and safety. SUMMARY OF BACKGROUND DATA: In patients with combined lumbar spinal stenosis and spondylolisthesis, it remains uncertain whether minimally invasive fusion surgery is noninferior to the open approach. MATERIALS AND METHODS: We conducted an open-label, noninferiority trial involving patients with symptomatic lumbar stenosis combined with low-grade spondylolisthesis. Patients were randomly assigned in a 1:1 ratio to undergo either MIS-TLIF or open TLIF surgery. The primary endpoint was the reduction in the Oswestry disability index (ODI) score from baseline to three months postsurgery, with a noninferiority margin of 12 points. Secondary outcomes included three-month changes from baseline in back and leg pain, neuropathic pain, satisfaction with treatment, intraoperative data, and cost-effectiveness. RESULTS: In the modified intention-to-treat population, the mean difference was 0.4, with the corresponding 90% CI of -5.7 to 6.5, having a lower bound below the noninferiority margin of 12. Similar results were obtained by analysis of the per-protocol population. 82.8% of patients achieved the MCID for the ODI. Results for secondary outcomes (clinical scales, complications) showed no significant differences between the treatment groups (all P >0.05). Although the open TLIF group had a hospital stay that was 1.5 days longer ( P =0.005) and required additional analgesia more frequently ( P =0.026), direct costs were 10.5% higher in the MIS-TLIF group ( P <0.001). CONCLUSIONS: This is the first high-quality study comparing open TLIF and MIS-TLIF with a validated primary endpoint. Among patients with combined lumbar degenerative stenosis and degenerative spondylolisthesis, MIS-TLIF resulted in clinical outcomes at three months that were noninferior to those with open TLIF.

Humans

Dual-Reporter Gene-Based Multimodal Imaging for Tracking Mesenchymal Stem Cells in Diabetic Skin Wound Repair.

BACKGROUND: Diabetic foot ulcer (DFU) is a clinically challenging complication characterized by poor healing outcomes, and conventional therapies provide limited benefit. Mesenchymal stem cell (MSC) transplantation offers a promising strategy for DFU repair. However, the low survival of transplanted MSCs in the hostile wound microenvironment, coupled with the lack of real-time, non-invasive methods to track these cells in vivo, severely hampers their therapeutic efficacy and clinical translation. METHODS: We engineered MSCs to co-express a dual reporter system comprising near-infrared fluorescent protein (iRFP) and ferritin heavy chain (FTH1). These modified cells were then integrated with a fibrin glue (FG) scaffold to create a unified platform that supports both multimodal imaging and therapeutic function within skin wounds. First, FTH1 overexpression enhances the antioxidant capacity of MSCs, while the FG scaffold provides structural support; this combination enhances cell survival and retention. Second, the iRFP/FTH1 dual reporter enables near-infrared fluorescence imaging and MRI-based localization, establishing a multimodal platform for real-time cell tracking. RESULTS: In a full-thickness skin defect model in diabetic mice, multimodal imaging revealed that transplanted cells persisted in the wound area for approximately seven days. Treatment with iRFP/FTH1-MSCs/FG significantly accelerated wound closure and promoted hair follicle regeneration and angiogenesis. Additionally, local iron deposition resulting from FTH1 expression enhanced fibroblast migration and collagen synthesis, further facilitating extracellular matrix remodeling. Mechanistic studies demonstrated that this therapy drives macrophage polarization toward the anti-inflammatory M2 phenotype and activates the PI3K-AKT-VEGF signaling pathway. These complementary effects synergistically enhance tissue regeneration and systematically improve diabetic wound healing. CONCLUSIONS: Collectively, this multimodal stem cell-scaffold system effectively integrates dynamic cell tracking with stem cell therapy during skin wound repair. It addresses a critical technical gap in visualizing stem cells within the wound microenvironment and provides valuable methodological and theoretical foundations for optimizing regenerative strategies for diabetic skin wounds.

Animals

Interactive gaming during inhalational induction of anesthesia reduces pediatric patient anxiety and improves induction compliance: A randomized controlled trial.

BACKGROUND: Preoperative anxiety affects up to 75% of pediatric surgical patients and is associated with adverse postoperative outcomes. Traditional anxiolytic strategies with premedication carry drawbacks including delayed recovery and paradoxical reactions, driving interest in non-pharmacologic alternatives. Audiovisual distraction represents one approach, encompassing passive methods (e.g. watching a video) and active modalities (e.g. interactive gaming). The Bedside Entertainment and Relaxation Theater (BERT) is a projection-based environment that enables audiovisual distraction during induction. Whether BERT-based interactive gaming reduces anxiety and improves induction compliance compared to standard perioperative care remains unknown. METHODS: This single-center RCT enrolled 74 pediatric patients aged 4 to 14 undergoing inhalational induction, randomized to standard care (SOC) or interactive gaming via BERT added to SOC during induction (BERT). The primary outcome was change in patient anxiety from baseline to induction, measured using the Modified Yale Preoperative Anxiety Scale (mYPAS). Secondary outcomes included caregiver anxiety, induction compliance, OR efficiency, opioid administration, and OR staff perceptions. RESULTS: Patients in the BERT group experienced significantly smaller increases in anxiety from baseline to induction than SOC (median mYPAS increase [IQR]: 0 [0 to 0] vs 10 [0 to 38], p&#xa0;<&#xa0;0.001). Induction compliance improved, with lower Induction Compliance Checklist (ICC) scores indicating fewer induction-related disruptive behaviors than SOC (median: 0 vs 1, shift -1 [95% CI: -2 to 0]; p&#xa0;=&#xa0;0.004). Caregiver anxiety increased less in the BERT group than SOC (mean STAI increase: 0.18 vs 1.89, difference&#xa0;-&#xa0;1.7, [95% CI: -3.2 to -0.26]; p&#xa0;=&#xa0;0.022). OR staff reported high acceptability, with 97% supporting continued use. No differences were observed in OR efficiency or opioid administration between groups. CONCLUSIONS: Interactive gaming via BERT attenuated increases in patient anxiety, improved induction compliance, and reduced the rise in caregiver anxiety without prolonging OR time. These findings support BERT as an effective, workflow-compatible anxiolytic strategy for pediatric inhalational induction.

Humans

A single session of high-definition transcranial direct current stimulation does not modulate effects of knee two-point discrimination training or sensorimotor function in healthy adults: Double-blind randomised controlled trial.

BACKGROUND: Benefits of sensory-training interventions on sensorimotor outcomes are inconsistent, and it is unclear whether transcranial direct current stimulation (tDCS) can enhance proprioception, which is fundamental to neuromuscular control. Existing evidence is dominated by upper-limb studies, so transferability to the knee is unclear. This study investigated whether a single session of anodal high-definition (HD)-tDCS, alone or combined with brief two-point discrimination (TPD) training, enhances knee sensorimotor function and performance in healthy adults. METHODS: In a double-blind randomised-controlled trial, 57 healthy participants received (1) 20-min, 1&#xa0;mA anodal HD-tDCS over the knee primary somatosensory (S1) map or sham stimulation, and (2) 15-min knee TPD training or no training. Knee somatosensory, sensorimotor, and functional performance measures were assessed pre- and immediately post-intervention. Three-way mixed-design ANOVAs, equivalence testing (smallest effect size of interest &#x3b7;2&#xa0;=&#xa0;0.02), Bayes factors, and linear mixed-effects models quantified effects. RESULTS: HD-tDCS, TPD training, and their sequential combination had no effect on any outcome measure (p&#xa0;&#x2265;&#xa0;0.05; &#x3b7;2&#xa0;&#x2264;&#xa0;0.015). Confidence intervals spanned equivalence bounds, and equivalence testing results were non-significant (p&#xa0;&#x2265;&#xa0;0.05). Bayes factors (<0.33) showed moderate evidence for the null (no effect). Mixed-effects modelling attributed &#x2264;8% of total variance to intervention fixed effects, with the remainder captured by participant-level random effects. CONCLUSION: A single 20-minute session of 1&#xa0;mA HD-tDCS, with or without brief TPD training, does not acutely modify knee somatosensory, sensorimotor, or functional performance in healthy adults. Existing evidence at the hand may not translate to the lower limb. Future work should investigate higher-dose, multi-session, task-concurrent, or network-targeted strategies in clinical populations.

Humans

Impact of Diabetes on Outcomes of Contemporary PCI Guided by OCT vs Angiography: The ILUMIEN IV Trial.

BACKGROUND: Patients with diabetes are at higher risk for adverse events after percutaneous coronary intervention (PCI) compared with patients without diabetes. OBJECTIVES: This study sought to assess the influence of diabetes and complex lesions on the outcomes of patients undergoing PCI with and without optical coherence tomography (OCT) guidance during a follow-up period of 2 years. METHODS: Patients in ILUMIEN IV randomized to OCT-guided vs angiography-guided PCI were grouped into those with (n = 1,044) and without diabetes (n = 1,443). Study endpoints were target vessel failure (TVF) and serious major adverse cardiovascular events (MACE). RESULTS: After adjustment for differences in clinical and angiographic characteristics, the 2-year rates of both TVF (9.9% vs 6.3%; adjusted HR: 1.48; 95% CI: 1.09-2.02; P = 0.01) and serious MACE (5.3% vs 2.7%; adjusted HR: 1.77; 95% CI: 1.14-2.76; P = 0.01) were increased in diabetic compared with nondiabetic patients, consistently in patients with and without complex lesions (Pinteraction = 0.22 and 0.14, respectively), although the highest 2-year rates were in patients with diabetes and complex lesions. In all randomized patients, OCT guidance compared with angiography guidance did not reduce TVF or serious MACE. These effects were consistent in patients with and without diabetes (Pinteraction = 0.41 and 0.20, respectively), and were not modified by treatment of complex lesions. CONCLUSIONS: In the large-scale ILUMIEN IV trial, patients with diabetes remained at increased risk for adverse events after PCI compared with nondiabetic patients despite the use of OCT procedural guidance. Patients with diabetes and complex lesions were at particularly high risk for adverse outcomes after PCI.

Humans

Cardiometabolic Multimorbidity Increases the Risk of Hip Fracture: A Longitudinal Cohort Study Based on CHARLS.

BACKGROUND: Cardiometabolic Multimorbidity (CMM) is defined as the co-occurrence of two or more conditions among heart disease, diabetes mellitus, stroke, and hypertension. Previous studies have shown associations between cardiometabolic diseases and fragility fractures; however, the relationship between CMM and hip fractures remains unclear in the Chinese population. This study therefore aims to investigate this association in a Chinese cohort to inform fracture prevention strategies. METHODS: This prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS) collected from 2011 to 2020. Participants from the 2011 baseline survey cohort were initially included. Subsequently, individuals were sequentially excluded if they were under 45&#x2009;years of age, had incomplete baseline CMM information, had a history of hip fracture, lost to follow-up, or had missing data on confounders. Kaplan-Meier survival analysis, Cox proportional hazards regression, subgroup analyses, and sensitivity analyses were performed to evaluate the association between CMM and the risk of hip fracture. RESULTS: A total of 6314 participants aged 45&#x2009;years and older were included, of whom 544 had CMM. Over a 9-year follow-up period, 287 incident hip fractures (4.55%) were identified. Among these, 36 participants had been diagnosed with CMM at baseline, whereas 251 had not. The incidence of hip fracture was significantly higher in participants with CMM than in those without CMM (13% vs. 8%, p&#x2009;=&#x2009;0.015). After full adjustment for confounders, multivariable Cox regression showed that CMM was associated with a 70% increased risk of hip fracture (HR&#x2009;=&#x2009;1.70, 95% CI: 1.318-2.47; p&#x2009;=&#x2009;0.005). Subgroup analyses indicated that age and history of falls were significant effect modifiers. The association between CMM and hip fracture was more pronounced in participants under 60&#x2009;years old (P for interaction&#x2009;=&#x2009;0.048) and those with a history of falls (P for interaction&#x2009;=&#x2009;0.014). CONCLUSION: These findings suggest that CMM increases the risk of hip fracture, particularly among relatively younger individuals and those with a history of falls.

Humans

Clinical Performance of Bulk-Fill Versus Incremental Composite Placement Approaches in Vital Posterior Teeth: A 24&#x2009;Months Randomized Controlled Trial.

BACKGROUND: Composite resin placement technique may influence marginal integrity, polymerization stress distribution, and long-term clinical performance of posterior restorations. This randomized controlled clinical trial evaluated the 24-month clinical performance of four different placement techniques in Class I posterior composite restorations. METHODS: Fifty patients aged 20-35&#x2009;years presenting with four occlusal carious lesions each were enrolled, resulting in 200 restorations. Cavities (4-5&#x2009;mm depth) were prepared according to caries extension. Restorations were randomly allocated into four equal groups (n&#x2009;=&#x2009;50) according to placement technique: stamp technique, snowplow technique, modified incremental "pizza" technique, and bulk-fill technique. All materials were applied following manufacturers' instructions. Clinical evaluation was performed at baseline and after 6, 12, and 24&#x2009;months using FDI criteria. Functional (fracture/retention, marginal adaptation), esthetic (marginal staining, anatomical form), and biological (postoperative sensitivity, secondary caries) properties were assessed by two calibrated evaluators. Statistical analysis was performed at a significance level of &#x3b1;&#x2009;=&#x2009;0.05. RESULTS: Thirty-eight patients with a total of 152 restorations were evaluated at the end of the 24&#x2009;months in line with FDI at the end of the study with 76% recall rates. No statistically significant differences were observed among groups regarding fracture/retention or secondary caries (p&#x2009;>&#x2009;0.05). Marginal adaptation and marginal staining demonstrated minor deterioration over time across all groups, with statistically significant intergroup differences found (p&#x2009;<&#x2009;0.05). Postoperative sensitivity was minimal and transient in all groups with no significant difference (p&#x2009;=&#x2009;0.181). CONCLUSIONS: Within the limitations of this 24-month follow-up, the four placement techniques demonstrated comparable clinical performance in Class I posterior composite restorations. Selection of technique may therefore be guided by clinical preference and procedural efficiency rather than differences in short-term clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07415317.

Humans

Tele-Oncology in the Post-Pandemic Era: Clinical Integration, Access Disparities and Medico-Legal Accountability.

PURPOSE OF THE REVIEW: Tele-health has evolved from a marginal tool confined to rural populations and selected follow-up programs into a structurally integrated component of modern cancer care. Prior to COVID-19, its adoption was constrained by regulatory fragmentation, non-uniform reimbursement, and licensure barriers. This narrative review evaluates the evolutionary integration of tele-health in oncology post-COVID-19, examines digital disparities across patient populations, and addresses the medico-legal implications of this integration, with the objective of providing a comprehensive and clinically actionable framework for the governance of virtual oncology care. RECENT FINDINGS: The pandemic acted as a global catalyst, driving telehealth to over 50% of oncology outpatient encounters in some settings, before stabilising post-pandemic at approximately 10-20% of consultations within hybrid care models. Evidence supports meaningful clinical benefits - improved access to specialist services, reduced travel burden, and sustained continuity of care - with outcomes comparable to in-person care in postoperative follow-up, symptom monitoring, and survivorship. However, persistent disparities in device availability, connectivity, and digital literacy disproportionately affect older, rural, and socioeconomically disadvantaged patients, raising the risk that geographic inequalities are replaced by technological ones. From a medico-legal standpoint, the remote modality does not modify the applicable standard of care, yet restricted physical examination and reliance on patient-reported data introduce risks of diagnostic delay and incomplete clinical assessment, with direct implications for professional liability, data protection under HIPAA and GDPR, cross-border licensure, and multi-party accountability across physicians, institutions, and technology providers. Tele-oncology has become a permanent structural feature of modern cancer care, offering demonstrable benefits in access, continuity, and patient satisfaction. Yet its integration has been uneven, its governance remains fragmented, and its medico-legal landscape is still evolving. Realising the full potential of virtual oncology care - equitably and safely - requires coherent regulatory frameworks, sustained investment in digital infrastructure, and explicit attention to the populations at greatest risk of being left behind.

Humans

Probiotic supplementation increases fecal TLR4 agonists without improving disease activity in juvenile idiopathic arthritis: a randomized placebo-controlled trial.

Gut dysbiosis has been implicated in the pathogenesis of juvenile idiopathic arthritis (JIA), suggesting that microbiota-targeted interventions may influence immune signalling during early immune development. We conducted the PERMAJI multicentre randomized, double-blind, placebo-controlled trial to evaluate the effects of probiotic supplementation (VSL#3) on host-microbiota immune interactions and disease activity in children with oligoarticular or RF-negative polyarticular JIA. Participants were randomly assigned (1:1) to receive VSL#3 or placebo for 3 months in addition to standard therapy. Stool and serum samples collected at baseline and month 3 were used to assess gut microbiota composition, fecal innate immune agonists, intestinal permeability, and systemic cytokines. The primary clinical endpoint was the proportion achieving an ACR Pedi 30 response at 3 months. Forty-four children were enrolled between September 2017 and July 2022. Clinical responses did not differ between groups (ACR Pedi 30: 47% with VSL#3 vs 63% with placebo; p&#x2009;=&#x2009;0.33), and conservative worst-case assumptions for missing data suggested lower response rates with VSL#3 (36% vs 68%; p&#x2009;=&#x2009;0.03). Probiotic supplementation significantly increased fecal Toll-like receptor 4 (TLR4) agonist activity, whereas gut microbiota diversity, intestinal permeability, and systemic cytokine levels remained unchanged. These findings indicate that probiotic supplementation can modify microbial innate immune signalling without detectable changes in microbial community diversity and may increase exposure to pro-inflammatory microbial stimuli in early-life autoimmune disease. The results highlight the complexity of host-microbiota immune interactions and underscore the need for careful evaluation of microbiome-targeted therapies in paediatric autoimmune disorders.

Humans

Relationship Between Number of Acute Pancreatitis Episodes and Risk of New-onset Diabetes in the U.S.: A Real-world Data Analysis.

INTRODUCTION: Acute pancreatitis (AP) is a common inflammatory disorder that is associated with increased risk for diabetes mellitus (DM). It remains unclear whether recurrent acute pancreatitis (RAP) is associated with further increased risk of incident DM. This study aims to investigate the association between RAP and incident DM using real-world data. METHODS: We conducted a retrospective cohort study using the MerativeTM MarketScan&#xae; claims database (2016-2023), identifying patients with AP and no prior history of DM at baseline. The primary exposure of interest, RAP, was defined as one or more episodes of AP occurring &#x2265;90 days after the index AP diagnosis, whereas one episode of AP referred to a single episode of AP (SAP) with no subsequent recurrence within 90 days following the index event. A multivariable stratified Cox proportional hazards regression models were used to determine the association between RAP and incident DM, identified using ICD-10 codes. RESULTS: In total, 16,184 individuals with AP (mean [SD] age: 45.8 [12.3]) contributed 40,712 person-years of follow-up, during which 1,477 incident cases of DM were documented. Individuals with RAP had an increased risk of incident DM compared with those with a SAP(adjusted HR, 1.92; 95% CI, 1.61-2.29). The risk increased significantly with the frequency of RAP. In comparing the modifying effect of patient demographics and comorbidities, a stronger association between RAP and incident DM was observed in females (adjusted HR, 2.44; 95% CI, 1.87-3.19) than in males (adjusted HR, 1.64; 95% CI, 1.30-2.07; Pinteraction=0.03). Also, stronger associations were observed among younger patients (18-46&#xa0;y) (adjusted HR=2.56; 95% CI, 1.97-3.31) and among non-tobacco abuse (adjusted HR=2.19; 95% CI, 1.81-2.65), with significant interactions for all comparisons (Pinteraction<0.05. CONCLUSIONS: In this real-world study, RAP was associated with an increased risk of incident DM. Our findings highlight an opportunity for glycemic monitoring and proactive management of patients with RAP to mitigate their risk of developing DM.

AP

Clinical performance of monolithic and veneered zirconia three-unit posterior FDPs: A five-year multicenter randomized controlled trial.

AIM: This randomized controlled clinical study compared monolithic, partially veneered, and fully veneered zirconia FDPs over a 5-year period with respect to survival, technical and biological complications, and patient-reported outcome measures (PROMs). MATERIALS AND METHODS: Sixty-four patients requiring three-unit posterior FDPs were randomly allocated to monolithic (MONO-FDP), partially veneered (PV-FDP), or fully veneered (FV-FDP) groups. All FDPs were fabricated from 4 mol% Y&#x2082;O&#x2083; partially stabilized zirconia (4Y-TZP). Follow-up examinations were conducted at baseline, 1, 3, and 5 years. Technical parameters were evaluated using modified USPHS criteria. Periodontal measurements (PPD, BOP, PI) and patient satisfaction were assessed at all time points. RESULTS: A total of 63 FDPs were evaluated at baseline, 57 at 3 years, and 54 at 5 years. Survival at 5 years was 94.7% for MONO-FDPs, 100% for FV-FDPs and 100% for PV-FDPs. Technical complications occurred exclusively in PV-FDP (33%) and FV-FDP (38%) groups and consisted of minor, polishable chipping; no chipping or fractures were recorded in MONO-FDPs (0%) with statistically significant difference between MONO-FDP and the other two groups (p &#x2264; 0.014). Biological parameters remained stable across all groups, with no significant differences in PPD, BOP, or PI. PV-FDPs and FV-FDPs tended to receive more favorable professional color ratings, whereas PROMs were similar among the groups. CONCLUSIONS: All three FDP designs-monolithic, partially veneered, and fully veneered-fabricated from 4Y-TZP zirconia demonstrated excellent 5-year clinical performance. Technical complications were limited to PV- and FV-FDPs and consisted of minor chipping. Biological outcomes and patient satisfaction were similar across groups. CLINICAL SIGNIFICANCE: The five-year outcomes suggest that veneered, partially veneered, and monolithic FDPs can be used with high clinical reliability; however, restorations incorporating veneering ceramic may present an elevated risk of ceramic chipping.

Humans