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Effects of Photobiomodulation Therapy in Lateral Luxation of Anterior Permanent Teeth: A Randomized, Double-Blind Clinical Trial.

BACKGROUND: Among the traumatic dental injuries (TDIs), lateral luxation may present poor prognosis due to frequent root resorption and consequent tooth loss. Photobiomodulation therapy (PBMT) modulates cellular activities (proliferation, differentiation, growth factor secretion) and may improve outcomes. OBJECTIVE: This randomized, double-blind, placebo-controlled trial evaluated PBMT (660 vs. 808&#x2009;nm) for post-operative pain and pulp sensitivity recovery in lateral luxation of permanent anterior teeth. METHODS: Initially, 41 patients were included, with a total of 63 teeth traumatized by lateral luxation and were allocated to G1 (n&#x2009;=&#x2009;21): Splinting&#x2009;+&#x2009;sham PBM (placebo), G2 (n&#x2009;=&#x2009;21): Splinting&#x2009;+&#x2009;808&#x2009;nm infrared PBM and G3 (n&#x2009;=&#x2009;21): Splinting&#x2009;+&#x2009;660&#x2009;nm red PBM. Four weekly sessions (3&#x2009;J/point, 3 points) were administered. Pain (by numeric rating scale) and pulp sensitivity (by cold test) were assessed weekly. Pain was analyzed using the Kruskal-Wallis test, followed by multiple comparisons using Dunn's method with Bonferroni correction, and pulp sensitivity by a logistic regression model (p&#x2009;<&#x2009;0.05). RESULTS: Three participants (total of 5 teeth) were excluded due to loss to follow-up. Fifty-eight teeth were analyzed (G1&#x2009;=&#x2009;21, G2&#x2009;=&#x2009;17, G3&#x2009;=&#x2009;20). Pain: All groups showed a significant reduction in pain over time (p&#x2009;<&#x2009;0.001). Both G2 and G3 demonstrated a significantly greater reduction in pain compared to G1 (p&#x2009;<&#x2009;0.001 and p&#x2009;=&#x2009;0.026, respectively). No significant difference in pain reduction was observed between G2 and G3. Pulp sensitivity: G2 showed a significant improvement over time (p&#x2009;<&#x2009;0.001), despite starting from a more unfavorable baseline. In contrast, no significant change in pulp sensitivity was observed for G1 or G3 between the initial and final assessments. CONCLUSION: Within the limitations of this clinical study, all intervention groups were effective in reducing pain in lateral luxation of permanent anterior teeth, with superior results for laser groups compared to the placebo. However, only the 808&#x2009;nm laser irradiation protocol demonstrated a significant improvement in pulp sensitivity, suggesting it may offer a more complete therapeutic response.

Humans

Exploring the role of successful exercise-induced body weight loss on cardiometabolic health in individuals with metabolic syndrome.

BACKGROUND AND AIM: High-intensity interval training (HIIT) is known to improve cardiorespiratory fitness (i.e., VO2MAX), a key marker of cardiometabolic health in individuals with metabolic syndrome (MetS). Nonetheless, body weight loss is widely recognized as a crucial factor in reducing insulin resistance and improving metabolic risk factors. Thus, we aimed to determine the importance of body weight loss following exercise training on improving MetS. METHODS AND RESULTS: Two hundred and twenty-eight adults (55.3&#xa0;&#xb1;&#xa0;7.9&#xa0;yr) with overweight/obesity (32.5&#xa0;&#xb1;&#xa0;4.6&#xa0;kg&#xb7;m-2) and MetS were randomized to: a) standard health care non-exercise group (CONTROL group, N=58) or b) standard health care plus 16 weeks of HIIT (EXER group, N=170). MetS (MetS z-score), insulin resistance (HOMA-IR), cardiorespiratory fitness (VO2PEAK), maximal cycling power (WPEAK), and body weight/composition were assessed. After intervention, EXER group participants were divided according to their weight loss response to training: i) those achieving the weight loss predicted from estimated exercise energy expenditure (-BW group, n=78; -3.3&#xa0;&#xb1;&#xa0;2.2&#xa0;kg); ii) those not reaching the expected weight loss (=BW group, n=38; -0.7&#xa0;&#xb1;&#xa0;0.5&#xa0;kg); iii) and those who gained weight (+BW group, n=54; 1.1&#xa0;&#xb1;&#xa0;1.0&#xa0;kg). VO2PEAK significantly improved regardless of body weight loss response (-BW, 0.3&#xa0;&#xb1;&#xa0;0.3; =BW, 0.2&#xa0;&#xb1;&#xa0;0.3; +BW, 0.3&#xa0;&#xb1;&#xa0;0.2&#xa0;L&#xb7;min-1; all p&#xa0;<&#xa0;0.001) compared to CONTROL group (0.0&#xa0;&#xb1;&#xa0;0.3&#xa0;L&#xb7;min-1). However, significant improvements in MetS z-score (-0.31&#xa0;&#xb1;&#xa0;0.41) and HOMA-IR (-0.7&#xa0;&#xb1;&#xa0;1.6) were observed only in the -BW group (both p&#xa0;<&#xa0;0.001). CONCLUSIONS: Exercise recommendations should consider that greater improvements in MetS are observed when interventions are accompanied by successful body weight loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05120778.

Humans

Electro-clinical efficacy and safety of midazolam in neonatal seizures: a systematic review with individual level exploratory analysis of gestational age-related treatment response.

UNLABELLED: Neonatal seizures are the most common neurological emergency during the neonatal period and are associated with increased mortality and adverse neurodevelopmental outcomes. Despite current recommendations supporting phenobarbital as first-line therapy, seizure control remains suboptimal in a large proportion of neonates, prompting the use of second-line antiseizure medications. Midazolam is increasingly administered in refractory neonatal seizures but evidence regarding its electro-clinical efficacy and safety remains limited and heterogeneous. To systematically review the available evidence on the electro-clinical efficacy and safety of midazolam in neonatal seizures and to perform an exploratory individual-level analysis investigating the association between gestational age and treatment response. A systematic review was conducted according to PRISMA 2020 guidelines. Studies including neonates with EEG- or aEEG-confirmed seizures treated with midazolam were included. Binary logistic regression was performed to assess the individual-level association between gestational age and treatment response. Eleven studies involving 146 neonates treated with midazolam were included. Electro-clinical response was observed in 101/146 neonates (69.2%), while seizure cessation was achieved in 61/146 neonates (41.8%). In an exploratory complete-case logistic regression analysis, higher gestational age appeared to be associated with a greater probability of electro-clinical response. The predicted probability curve crossed the 50% response probability at approximately 36.5&#xa0;weeks of gestation. Hypotension was the most frequently reported adverse event, while respiratory depression, sedation-related effects, and transient EEG/aEEG suppression were reported less frequently. CONCLUSIONS: Midazolam may have a role as an add-on antiseizure medication in neonatal seizures, particularly in refractory cases. However, the evidence remains limited by heterogeneity in study design, EEG monitoring strategies, outcome definitions, and incomplete individual-level data. The observed association between gestational age and response is hypothesis-generating and requires prospective validation. WHAT IS KNOWN: &#x2022; Phenobarbital often provides incomplete seizure control in neonates, making second-line antiseizure therapies necessary in refractory cases. &#x2022; Evidence supporting midazolam for neonatal seizures remains limited and heterogeneous. WHAT IS NEW: &#x2022; This systematic review summarizes the electro-clinical efficacy and safety of midazolam and includes an exploratory patient-level analysis suggesting that higher gestational age may be associated with improved treatment response. &#x2022; These findings support further prospective studies on developmental determinants of response to GABAergic therapy.

Humans

Comparison of analgesic treatments used for ankle sprains in the emergency department.

BACKGROUND: Ankle sprains (ASs) account for approximately 5% of emergency department visits and 40% of all sports-related injuries, causing significant pain and restriction in the range of motion (ROM). This study aims to observe the clinical outcomes of early administration of intravenously administered paracetamol, ibuprofen, and dexketoprofen, which are frequently used in emergency department practice for ASs. For this purpose, pain monitoring and ROM measurements were performed to demonstrate the effectiveness of early functional analgesia. METHODS: This prospective, randomized, double-blind study was conducted between December 2023 and May 2024 on patients diagnosed with grade 1-2 ASs in the emergency department. Patients were divided into three groups and received intravenous dexketoprofen (Group D, n=52), paracetamol (Group P, n=52), and ibuprofen (Group I, n=51). Pain assessment was performed using the numeric rating scale (NRS) and the Wong-Baker FACES Pain Scale (WBS). ROM was evaluated by measuring dorsiflexion ROM (d-ROM) and plantar flexion ROM (p-ROM) angles using a semicircular goniometer. Pre-treatment and 1-h post-treatment measure-ments were compared. RESULTS: In the post-treatment pain assessment, no significant difference was observed between the groups in terms of NRS scores (p=0.352); however, Group I had the lowest WBS scores (p<0.001). Nevertheless, in all three groups, post-treatment pain scores (NRS and WBS) were significantly lower compared to pre-treatment values (p<0.001). Regarding ROM, pre-treatment d-ROM and p-ROM values were similar among the groups (p=0.196) and p=0.287, respectively). Post-treatment measurements revealed that d-ROM was lower in Group I (p=0.034), whereas p-ROM was higher (p=0.011). However, in all groups, ROM values significantly improved after treatment compared to baseline (p<0.001). When pre- and post-treatment changes (&#x394;) in pain scores and ROM values were compared, no statistically significant differences were found between the groups (&#x394;NRS p=0.264, &#x394;WBS p=0.965, &#x394;d-ROM p=0.099, &#x394;p-ROM p=0.073). CONCLUSION: Paracetamol, ibuprofen, and dexketoprofen demonstrated similar efficacy in reducing pain and improving ankle joint ROM during the acute phase of ASs. These findings suggest that the early initiation of analgesic treatment in ASs contributes to clinical recovery.

Humans

Impact of Commercial Artificial Intelligence on Radiologist Reading Time for Pulmonary Nodule Evaluation at Chest CT.

Background Chest CT is a primary method for identifying pulmonary nodules, yet interpreting scans remains time-intensive and demanding. Currently, artificial intelligence (AI) is expected to reduce reading times, but the effect of AI on reporting times in this setting is unknown. Purpose To evaluate the impact of a commercial AI software on radiologists' reading time for pulmonary nodule assessment on chest CT scans within a real-world clinical setting. Materials and Methods This retrospective study included patients who underwent chest CT examinations at a tertiary medical center between September 2021 and May 2024. The study period was divided into pre- and post-AI phases. The primary outcome was radiology reporting time. The association between AI implementation and reporting time was evaluated using a multivariable parametric Weibull shared frailty survival model adjusted for reader function, examination type, patient location, and requesting specialty, with clustering at the radiologist level. Interaction analyses assessed heterogeneity across prespecified subgroups. An exploratory extrapolation estimated projected workforce and financial impact. Results This study included 19&#x2009;433 patients (mean age, 62 years &#xb1; 14.2 [SD]; 21&#x2009;814 men; 39&#x2009;323 chest CT examinations, 19&#x2009;190 pre-AI, and 20&#x2009;133 post-AI). AI implementation was associated with faster report completion (adjusted hazard ratio, 1.17; 95% CI: 1.14, 1.21; P < .001). The adjusted median reporting time decreased from 21.3 minutes pre-AI to 18.2 minutes post-AI (14.6% reduction; P < .001). Heterogeneity was observed across reader function (P < .001), examination type (P = .048), and requesting specialty (P = .03). The largest relative reductions were observed for CT thorax electrocardiogram-gated examinations (-41.1%; P < .001) and thoracic radiologists (-25.0%; P < .001), whereas emergency department examinations showed increased median reporting time (7.1%; P < .001). At institutional scan volumes (approximately 20&#x2009;000-22&#x2009;000 chest CT examinations annually), exploratory modeling suggested an approximate reduction of 0.5 full-time equivalent radiologist workload. Conclusion Implementation of commercial AI-assisted pulmonary nodule assessment on chest CT scans reduced radiologist reporting time in a real-world clinical setting. &#xa9; The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Iwasawa in this issue.

Humans

Safety and Tolerability of Oral Islatravir Once Monthly as Pre-exposure Prophylaxis in Cisgender Men and Transgender Women Who Have an Elevated Likelihood of HIV-1 Exposure: Results From the IMPOWER-24 Randomized Phase 3 Study.

BACKGROUND: Islatravir once monthly (qm), a nucleoside reverse transcriptase translocation inhibitor with a long half-life, was evaluated for safety and tolerability in cisgender men and transgender women who have sex with men and are at increased likelihood of HIV-1 (HIV) exposure. METHODS: IMPOWER-24 (NCT04652700) was a double-blind, Phase 3 study. Participants were randomized 2:1 to islatravir 60 mg oral qm or emtricitabine (FTC; 200 mg) coformulated with either tenofovir disoproxil (245 mg) or tenofovir alafenamide (TAF; 25 mg) once daily (qd). After &#x223c;9 months, blinded islatravir was discontinued due to lymphocyte reductions; participants were offered open-label comparator for 20 months. RESULTS: In total, 494 participants were enrolled (328 islatravir; 166 comparator): 91.5% were cisgender men, 41.7% were White, and median age was 27 years. Mean blinded dosing duration was 4.7 months (islatravir) versus 4.3 months (comparator). Overall, 211 participants (64.3%) in the islatravir group and 128 (77.1%) in the comparator group had &#x2265;1 adverse event (AE). Most AEs were mild or moderate, with 1 AE leading to product discontinuation (islatravir; gastroesophageal reflux). Serious AEs occurred in <2%; none were related to study product. Change in total lymphocytes in the islatravir group at Month 3 was -7.4%; a trend toward recovery was observed after islatravir was stopped. Mean total lymphocytes remained within normal range. No HIV infections occurred in either group during the double-blind phase. CONCLUSIONS: Islatravir qm was generally well tolerated; decreases in total lymphocytes were observed with islatravir. Original primary efficacy objectives were not assessed due to early study stoppage.

Humans

Associations of Illness Perception, Resignation Coping, and Social Support With Self-Regulatory Fatigue in Patients With Type 2 Diabetes: A Cross-Sectional Study.

AIMS: To examine the associations among illness perception, resignation coping, social support, and self-regulatory fatigue (SRF) in patients with Type 2 diabetes mellitus. The study specifically explores whether resignation coping and social support exhibit indirect associations with SRF in the context of illness perception. DESIGN: A cross-sectional study. METHODS: From November 2024 to October 2025, a convenience sample of 302 adult patients with T2DM was recruited from a tertiary general hospital in China. Participants completed validated instruments with established psychometric properties, namely the Brief Illness Perception Questionnaire, the Medical Coping Modes Questionnaire, the Perceived Social Support Scale, and the Self-Regulatory Fatigue Scale. Statistical analyses included Spearman correlation and serial mediation analysis using the PROCESS Macro (Model 6) with bias-corrected bootstrapping. RESULTS: SRF was positively correlated with negative illness perception (r&#x2009;=&#x2009;0.579, p&#x2009;<&#x2009;0.01) and resignation coping (r&#x2009;=&#x2009;0.612, p&#x2009;<&#x2009;0.01), and negatively correlated with social support (r&#x2009;=&#x2009;-0.598, p&#x2009;<&#x2009;0.01). Serial mediation analysis revealed that illness perception was associated with SRF through indirect pathways involving resignation coping and social support. Resignation coping and social support mediated the association between illness perception and self-regulatory fatigue, both individually and sequentially. CONCLUSIONS: Negative illness perception correlates with higher SRF. This observed correlation is additionally linked to indirect pathways involving resignation coping and lower social support. Collectively, these findings highlight a pattern of interrelated cognitive (illness perception), behavioural (resignation coping), and resource (social support) factors that are associated with self-regulatory fatigue in this cross-sectional study. IMPLICATIONS FOR THE PROFESSION: The findings offer a clear, evidence-based framework for nursing practice. They highlight the potential value of integrated assessment and intervention that simultaneously addresses patients' illness beliefs, maladaptive coping strategies, and social support systems, which are associated with lower SRF and better diabetes self-management. REPORTING METHOD: This study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: Patients participated solely as research participants by providing survey data. They were not involved in the study design, implementation, data analysis, interpretation, or manuscript preparation. All patients provided written informed consent prior to questionnaire completion.

Humans

Risk Factors and Predictive Model for Postoperative High Myopia in Children Undergoing Congenital Cataract Surgery With Intraocular Lens Implantation.

PURPOSE: To identify risk factors associated with the development of high myopia following congenital cataract surgery and to establish a robust predictive model. DESIGN: Retrospective clinical cohort study. SUBJECTS: This retrospective study included 106 pediatric patients who underwent congenital cataract surgery with primary IOL implantation (mean follow-up 8.19 years). The model was externally validated in an independent cohort of 72 patients with a mean follow-up of 7.83 years. METHODS: Preoperative and postoperative ocular biometric parameters were collected. Risk factors for postoperative high myopia were analyzed using Cox proportional hazards regression, which served as the basis for model construction. The predictive performance of the model was rigorously evaluated for discrimination and calibration. Discriminative ability was quantified using Harrell's C-index and the area under the receiver operating characteristic curve (AUC). Model calibration was assessed via calibration plots by comparing predicted probabilities with actual observed outcomes. Internal validation was performed using a bootstrapping method (500 iterations) to ensure model stability and adjust for potential overfitting. RESULTS: An initial postoperative refraction of <+0.75D, and a higher IOL Power to Axial length Ratio (IOL/AL ratio) were identified as significant risk factors for the development of postoperative high myopia. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. The predictive model demonstrated robust performance, achieving a C-index of 0.711 (internal validation C-index: 0.713). The area under the receiver operating characteristic curve (AUC) values for predicting high myopia at 5 and 10 years were 0.858 and 0.745, respectively. Furthermore, calibration curves demonstrated excellent agreement between the predicted and observed outcomes throughout the follow-up period. In external validation, the model achieved a C-index of 0.825, 5-year AUC of 0.833, and 10-year AUC of 0.713. CONCLUSIONS: Our analysis established that initial postoperative refraction <+0.75D, and an elevated IOL/AL ratio are key determinants of high myopia risk following surgery. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. This predictive framework provides clinicians with a practical tool to optimize preoperative IOL selection and identify high-risk infants who require vigilant myopia prevention and balanced amblyopia management.

Humans

Characteristics of post-exercise responders versus non-responders following aerobic or isometric exercise in physically inactive adults of African and South Asian descent with high-normal blood pressure or grade I hypertension.

OBJECTIVE: To investigate interindividual variability in post-exercise hypotension (PEH) and to characterise cardiovascular and autonomic differences between responders and non-responders following aerobic and isometric exercise in adults of African and South Asian descent with elevated blood pressure (BP). METHODS: Physically inactive adults of African and South Asian descent living in Suriname (18-65&#x2009;years) with high-normal BP or grade I hypertension participated in a randomised controlled crossover trial. In this randomised cross-over trial, 47 adults (50.1&#x2009;&#xb1;&#x2009;10.8&#x2009;years; 38% male) with high-normal blood pressure or grade I hypertension completed three conditions: aerobic exercise (30&#x2009;min at 40-60% heart rate reserve), isometric handgrip exercise, and a non-exercise control. Ambulatory BP was assessed over 24&#x2009;h. PEH was defined as the net effect: (post-exercise&#x2009;-&#x2009;pre-exercise) - (post-control&#x2009;-&#x2009;pre-control). Participants were classified as responders if daytime BP decreased &#x2265;5&#x2009;mmHg. Arterial stiffness, cardiac, and autonomic parameters were assessed. RESULTS: Following aerobic exercise, 46% of participants were classified as systolic responders compared with 28% after isometric exercise. No baseline differences were observed in demographic or clinical characteristics between responders and non-responders, suggesting that PEH variability may reflect underlying physiological rather than clinical differences. Aerobic responders demonstrated greater reductions in aortic augmentation index (-19.4% vs. -10.9%, p&#x2009;=&#x2009;0.05), larger increases in stroke volume (+8.1 vs. -5.3&#x2009;mL, p&#x2009;=&#x2009;0.05) and cardiac output (+1.54&#x2009;&#xb1;&#x2009;1.89 vs. +0.58&#x2009;&#xb1;&#x2009;1.60&#x2009;L/min, p&#x2009;=&#x2009;0.009), and more favourable autonomic recovery. Among all variables, only the change in cardiac output was associated with PEH magnitude (r&#x2009;=&#x2009;-0.46, p&#x2009;=&#x2009;0.006). No consistent physiological differences were observed following isometric exercise. CONCLUSION: PEH following aerobic exercise is characterised by a distinct responder phenotype associated with greater reductions in aortic augmentation index and favourable cardiac adaptations. These findings highlight substantial interindividual variability in BP responses and support the need for individualised exercise strategies in hypertension management.

Adolescent

[Clinical efficacy and cost-effectiveness evaluation of acupoint thread-embedding for knee osteoarthritis of early to middle stage].

OBJECTIVE: To compare the clinical efficacy of acupoint thread-embedding and electroacupuncture for knee osteoarthritis (KOA) of early to middle stage, and to evaluate their economic benefits based on cost-effectiveness analysis. METHODS: A total of 66 patients with KOA of early to middle stage were randomized into an acupoint thread-embedding group (33 cases, 1 case dropped out) and an electroacupuncture group (33 cases, 2 cases dropped out). In the acupoint thread-embedding group, acupoint thread-embedding was applied at Xuehai (SP10), Liangqiu (ST34), Weizhong (BL40), etc.on the affected side, once a week. In the electroacupuncture group, electroacupuncture was applied at Xuehai (SP10),Liangqiu (ST34), Zusanli (SP36), etc. on the affected side, with disperse-dense wave, in frequency of 2 Hz/100 Hz, once every other day, 3 times a week. Both groups were treated for 4 weeks. The Western Ontario and McMaster Universities arthritis index(WOMAC) score was observed before and after treatment, as well as at the follow-up of 4 weeks after treatment completion,the visual analogue scale (VAS) score of pain and the Lysholm score were observed before and after treatment in the two groups. The clinical efficacy was evaluated between the two groups, and the cost-effectiveness analysis was conducted based on WOMAC score. RESULTS: After treatment, the WOMAC and pain VAS scores were decreased compared with those before treatment (P<0.001), and the Lysholm scores were increased compared with those before treatment (P<0.001) in both groups. At follow-up, the WOMAC score in the acupoint thread-embedding group was decreased compared with that before treatment (P<0.001), and was lower than that in the electroacupuncture group (P<0.05). The total effective rates were 93.8% (30/32) in the acupoint thread-embedding group and 87.1% (27/31) in the electroacupuncture group, with no statistically significant difference between the two groups (P>0.05). The cost-effectiveness ratio (CER) and the total cost of the acupoint thread-embedding group were lower than those in the electroacupuncture group. CONCLUSION: Both acupoint thread-embedding and electroacupuncture can improve knee joint function, pain and stability in patients with KOA of early to middle stage, with comparable efficacy, and the acupoint thread-embedding group shows better long-term efficacy, lower cost and higher economic benefit.

Humans

First insights into the role of evolutionary history in shaping venom composition of Vipera ammodytes.

Understanding intraspecific venom variation requires distinguishing the contributions of neutral population history from natural selection. This study aims to determine whether venom variation in Vipera ammodytes species complex is structured across eight phylogenetic groups. Despite a complex evolutionary history, venom composition did not differ among phylogenetic groups within the analytical framework used, suggesting that shared ancestry alone does not explain venom variation. Whether local adaptation to environmental conditions explains the observed variation remains an open question for future studies.

Animals

Comparative Efficacy of Insulin and Alternative Therapies for Hypertriglyceridemia-Associated Acute Pancreatitis: A Systematic Review and Network Meta-Analysis.

BACKGROUND AND AIMS: Hypertriglyceridemia-induced acute pancreatitis is associated with high triglyceride levels and may lead to significant clinical complications. Rapid TG-lowering strategies, including insulin, therapeutic plasma exchange (TPE), heparin, hemofiltration, and conservative management, are used in clinical practice; however, their comparative efficacy and impact on clinical outcomes remain uncertain. METHODS: Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and International Prospective Register of Systematic Reviews (PROSPERO) registration (CRD420251239674), we searched PubMed, Embase, Web of Science, Scopus, CINAHL, Google Scholar, and Cochrane. Primary outcomes included TG reduction, C-reactive protein (CRP), length of stay, mortality, and organ failure. Secondary outcomes included renal and respiratory failure. Random-effects network meta-analyses estimated mean differences or relative risks with 95% confidence intervals; treatments were ranked using the Surface Under the Cumulative Ranking curve (SUCRA). Predefined sensitivity analyses were conducted according to study design (RCTs) and risk of bias (ROB). RESULTS: Across predominantly observational evidence, no intervention demonstrated statistically significant superiority over insulin-based therapy for mortality, organ failure, or length of stay, and no consistent clinical benefit was observed despite differences in biochemical TG reduction. Although some interventions showed relatively favorable SUCRA rankings across selected outcomes, these findings were not consistently supported by statistically significant or high-certainty evidence. In RCT-restricted analyses, therapeutic plasma exchange (TPE) significantly reduced TG levels versus insulin (MD&#x2009;-&#x2009;620.0; p&#x2009;=&#x2009;0.03) and CRP versus conservative therapy (MD&#x2009;-&#x2009;0.80; p&#x2009;<&#x2009;0.01), while insulin plus heparin was associated with shorter hospital stay (MD&#x2009;-&#x2009;1.60&#xa0;days; p&#x2009;<&#x2009;0.01). However, faster triglyceride reduction did not consistently translate into improved mortality, organ failure, ICU-related outcomes, or length of stay. CONCLUSION: Despite improvements in biochemical markers, the clinical significance of rapid TG reduction in HTG-AP remains uncertain, as these effects were not consistently associated with improvements in mortality, organ failure, ICU-related outcomes, or hospital length of stay. Given that most available evidence was derived from nonrandomized studies and that the certainty of evidence was predominantly low or very low, adequately powered randomized controlled trials are needed to determine whether accelerated triglyceride lowering improves clinically meaningful patient outcomes.

Humans

Ultrashort vs Standard-Duration Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients Undergoing PCI: A Meta-Analysis.

BACKGROUND: The efficacy and safety of ultrashort (&#x2264;1-month) dual antiplatelet therapy (DAPT) followed by antiplatelet monotherapy remain uncertain in acute coronary syndrome (ACS) patients. OBJECTIVES: This study sought to compare ultrashort vs standard-duration DAPT in patients with ACS undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials until February 15, 2026. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), major bleeding, and net adverse clinical event (NACE). Prespecified subgroup analyses examined by ethnicity (East Asian vs non-East Asian) and abbreviation strategy (intensive: &#x2264;1-week DAPT or clopidogrel/aspirin monotherapy vs moderate: &#x2265;2-week DAPT, followed by ticagrelor/prasugrel monotherapy). RESULTS: Across 10 trials (n = 29,232), ultrashort DAPT did not increase MACCE risk (HR: 1.06; 95% CI: 0.93-1.20; P = 0.38; I2 = 24%), with higher MACCE risk observed in ST-segment elevation myocardial infarction (STEMI) but not non-ST-segment elevation ACS (NSTE-ACS), and significantly reduced major bleeding (HR: 0.47; 95% CI: 0.35-0.64; P < 0.00001; I2 = 44%), resulting in a net clinical benefit (HR: 0.83; 95% CI: 0.72-0.97; P = 0.02; I2 = 61%). Bleeding reduction was more pronounced in East Asians (HR: 0.35; 95% CI: 0.25-0.49; P < 0.00001; I2 = 0%) than non-East Asians (HR: 0.63; 95% CI: 0.43-0.93; P = 0.02; I2 = 44%), with a significant interaction (P = 0.02). The abbreviation strategy significantly modified outcomes (P for interaction = 0.003): intensive abbreviation raised MACCE risk (HR: 1.37; 95% CI: 1.11-1.69; P = 0.003; I2 = 0%), while moderate abbreviation had no statistically significant difference (HR: 0.96; 95% CI: 0.85-1.08; P = 0.47; I2 = 0%). CONCLUSIONS: In patients with ACS undergoing PCI, ultrashort DAPT reduced bleeding without increasing ischemic events overall, although a signal of increased MACCE was observed in STEMI but not in NSTE-ACS. Bleeding reduction was greater in East Asians, while &#x2264;1-week DAPT or clopidogrel/aspirin monotherapy may increase ischemic risk.

Humans

Changes in hippocampal functional connectivity and volume associated with cognitive improvement and decline in amnestic mild cognitive impairment following computerized cognitive training.

BACKGROUND: The hippocampus influences the outcomes of amnestic mild cognitive impairment (aMCI) and undergoes different changes during the cognitive decline or recovery of aMCI compared to elderly individuals with normal cognition, which may reveal disease-dependent neurodegeneration or plasticity. We first aimed to investigate the hippocampal changes associated with cognitive changes in aMCI using a combined case-control study design. METHODS: In total, 50&#x202f;aMCI individuals and 50 healthy controls (HCs) were recruited in Shenyang, China, and separately randomized into training and control groups: aMCI training group, aMCI no training group, HC training group, and HC no training group. The aMCI and HC training groups received computerized cognitive training (CCT) thrice weekly for 12 weeks. Cognitive assessments and MRI data were collected at baseline and follow-up. RESULTS: The primary outcome was significant CCT&#xd7;diagnosis interaction effect on the change in cognitive performance as measured by clock drawing test (CDT) scores (F&#x202f;=&#x202f;4.322, P&#x202f;=&#x202f;0.041); this interaction was driven by CCT specifically in aMCI (F&#x202f;=&#x202f;4.465, P&#x202f;=&#x202f;0.038). Significant CCT&#xd7;diagnosis interaction effects of right-hippocampal FC changes were observed in the bilateral precuneus/cuneus (Pvoxel<0.05) driven by CCT in aMCI (F&#x202f;=&#x202f;5.429, P&#x202f;=&#x202f;0.023), and in the left superior temporal gyrus/middle temporal gyrus (STG/MTG, Pvoxel<0.05), driven by CCT of only in HCs (F&#x202f;=&#x202f;6.587, P&#x202f;=&#x202f;0.013). A significant interaction effect of left-hippocampal FC changes were observed in the right triangular part of the inferior frontal gyrus (IFGtriang, Pvoxel<0.05), driven by CCT in aMCI and HCs (F&#x202f;=&#x202f;6.550, P&#x202f;=&#x202f;0.013; F&#x202f;=&#x202f;7.097, P&#x202f;=&#x202f;0.010). No significant interaction effect on the change in hippocampal GMV was noted (P&#x202f;>&#x202f;0.05). CONCLUSION: CCT can improve the visuospatial ability of aMCI, which is reflected by the CDT scores. CCT can alter hippocampal FC in the bilateral precuneus/cuneus, the right IFGtriang, and the left STG/MTG. The hippocampal GMV is difficult to change in both HCs and aMCI during the cognitive decline. REGISTRATION NUMBER: ChiCTR1900026849. DATE OF REGISTRATION: 24 October 2019 NAME OF TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR).

Humans

A Novel Multiple Sensory Nerve Block Combination Using Ultrasound Guidance in Knee Arthroplasty: A Randomized Clinical Trial.

INTRODUCTION: Combining adductor canal block (ACB), infiltration between the popliteal artery and posterior capsule of the knee (IPACK), and genicular nerve blocks provides motor-sparing analgesia in total knee arthroplasty (TKA). Adding nerve blocks targeting the nerve to vastus medialis, vastus intermedius, and anterior femoral cutaneous nerve may improve postoperative pain management without affecting mobility. This study evaluated the effect of an eight-nerve block combination for pain relief after TKA versus local infiltration analgesia (LIA). METHODS: Participants were randomized into intervention or standard treatment groups. The intervention group received an eight-nerve block combination using 40 mL ropivacaine, 5&#x2009;mg/mL, with 75 &#xb5;g of clonidine. The control group received LIA comprising 150 mL ropivacaine, 2&#x2009;mg/mL, supplemented with 0.5&#x2009;mg adrenaline. The primary outcome was postoperative pain intensity, measured by the numeric rating scale (NRS) at postanesthesia care unit (PACU) arrival, 1 hour, 2 hours after PACU arrival, at ward arrival, evening of surgery, morning of postoperative day 1 (POD1), and at 14:00 POD1. Statistical analysis was performed using the Mann-Whitney U test. Secondary outcomes included 48-hour oral morphine equivalent (OME) consumption and length of hospital stay (LOS). RESULTS: A total of 217 patients scheduled for TKA were randomized. No significant differences were observed in the primary outcome. NRS at rest, presented as median (IQR), did not differ between groups at any time point. At PACU arrival 0 (0-3) vs 0 (0-4), at 1 hour 2 (0-4) vs 2 (0-5), at 2 hours 2 (0-6) vs 2.5 (0-4), at ward arrival 3 (2-5) vs 3 (2-5), on the evening of POD0 4 (3-5) vs 3.5 (2-6), on the morning of POD1 4 (3-6) vs 4 (2-5), and at 14:00 POD1 3 (2-5) vs 3 (2-5) for nerve block and LIA groups, respectively (all P > .05). Exploratory secondary outcomes indicated reduced 48-hour OME consumption presented as median (IQR), 70&#x2009;mg (52.5-96.3), vs 96&#x2009;mg (61.3-148.8); P = .008) and shortened hospital stay, median (IQR), 1 day (1-2), vs 2 days, (1-3); P < .001) in the nerve block group compared to the LIA group. CONCLUSIONS: No differences were observed in pain scores between the eight-nerve block combination and LIA. Secondary outcomes revealed a reduction in 48-hour opioid consumption and a modestly shorter hospital stay with nerve block compared to LIA.

Humans

Impact of a thermal care bundle on peri-operative hypothermia, surgical site infection, and readmissions in osteosynthesis patients: A randomised controlled trial.

BACKGROUND: Maintaining normothermia throughout the peri-operative period prevents the occurrence of complications related to hypothermia. OBJECTIVE: To determine the effect of a thermal care bundle with a short prewarming period on inadvertent peri-operative hypothermia (IPH), surgical site infection (SSI), and unplanned readmission among osteosynthesis patients, and to identify associated variables. DESIGN: Open-label, randomised controlled trial. SETTING: University hospital. PATIENTS: One hundred and forty-eight patients who underwent osteosynthesis surgery. INTERVENTION: The intervention group received the thermal care bundle, which consisted in prewarming patients 10&#x200a;min before anaesthesia delivery and maintaining body temperature with a forced air device during surgery and the immediate postoperative period; in addition, the operating room environmental temperature was kept at 21&#x200a;&#xb0;C, and fluids were warmed to 38&#x200a;&#xb0;C. MAIN OUTCOME MEASURES: For the primary objective, hypothermia was defined as core body temperature below 36&#x200a;&#xb0;C and measured using the 3M Spot On zero heat flux sensor. Core temperature was recorded upon admission to the pre-operative holding area and subsequently every 30&#x200a;min until postanaesthesia care unit (PACU) discharge. Secondary objectives were SSI and readmissions: a follow-up at 30 to 60 and 90&#x200a;days was performed by the principal investigator. RESULTS: All 148 patients completed the study, and there were no significant differences between the groups at baseline. At the start of surgery, the incidence of hypothermia was significantly lower in the bundle group (1.3 vs. 9.9% among controls; odds ratio&#x200a;=&#x200a;7.59, P &#x200a;=&#x200a;0.021). A significantly lower incidence of hypothermia was also observed at admission to the PACU (14.3% in the bundle group vs. 29.6% among controls; odds ratio&#x200a;=&#x200a;2.07; P &#x200a;=&#x200a;0.024). Application of the bundle increased patients' core body temperature by 0.13&#x200a;&#xb0;C (95% confidence interval (CI), 0.003 to 0.254; P &#x200a;=&#x200a;0.045). Patients in the bundle group had a slightly lower observed incidence of wound infections requiring readmission (odds ratio&#x200a;=&#x200a;0.35; 95% CI, 0.04 to 2.92), although this difference was not statistically significant ( P &#x200a;=&#x200a;0.332). CONCLUSIONS: The bundle reduces peri-operative hypothermia by up to 59%, but does not affect on SSI; factors like presurgery hospital stay, operating room and PACU occupancy were identified as risk factors for SSI. REGISTRATION: 21 July 2022: NCT05469958 (Clinical Trials.gov), first recruitment 15 August 2022.

Adult

Adding Rib Mobilization to Diaphragm Release Techniques in Patients With Non-Specific Neck Pain: Randomized Controlled Trial.

BACKGROUND: Non-specific neck pain (NSNP) is a frequent issue that can negatively affect both mobility and function. Recently, there has been growing interest in newer therapeutic approaches, including rib mobilization and diaphragm release techniques, as potential ways to address NSNP and support better outcomes for those affected. PURPOSE: To find out the immediate effects of how (DRT) combined with (RMT) affects the level of pain and the extent to which patients' functional abilities are improved in cases of NSNP. METHODS: For this prospective RCT, 96 participants aged 20 to 45&#xa0;years were randomly assigned to one of three equal groups based on their pain score (VAS). Group B engaged in (DRT) for 40&#xa0;minutes, three times weekly for 8&#xa0;weeks, in contrast to Group A, which got both RMT combined with DRT. Group C (active control) received advice and some exercises. Measurements were collected before and after the intervention; the primary outcomes included pain severity, evaluated using a visual analog scale (VAS); active neck range of motion (ROM), measured with a cervical range of motion (CROM) device; and neck flexion endurance. Additionally, the secondary outcome of neck-related disability was assessed using the Neck Disability Index (NDI). RESULTS: No statistically significant difference was identified among the three groups at baseline; nevertheless, a treatment effect emerged after 8&#xa0;weeks (p&#xa0;=&#xa0;0.001 and f-value&#xa0;=&#xa0;4.15, &#x19e;2&#xa0;=&#xa0;0.306). A statistically significant time-treatment interaction was seen when comparing the pre- and post-treatment periods in groups A and B (p&#xa0;=&#xa0;0.001, f-value&#xa0;=&#xa0;3.16, &#x19e;2&#xa0;=&#xa0;0.251). CONCLUSION: The addition of rib mobilization to diaphragm release techniques in patients with non-specific neck pain resulted in statistically significant improvements in pain intensity, cervical flexion, right lateral rotation, left lateral rotation, right rotation, and neck flexor endurance, with moderate to large effect sizes for pain reduction and cervical motion. However, no statistically significant differences were observed between groups for cervical extension, left rotation, or the Neck Disability Index (NDI), and only a marginal clinical improvement in NDI was noted in Group A. The observed benefits in the combined intervention group may not be attributable solely to rib mobilization. The increased treatment complexity and greater therapist interaction inherent in the combined approach could also have influenced the outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07133646.

Humans

Gout and allopurinol adherence in newly diagnosed patients and the risk of fractures: a nationwide cohort study.

INTRODUCTION / OBJECTIVES: The association between gout and fractures remains controversial due to the competing effects of uric acid's antioxidant properties and gout-induced chronic inflammation. Our study aimed to evaluate the risk of fractures in newly diagnosed gout patients and to analyze the impact of Allopurinol medication adherence on this risk. METHODS: This nationwide cohort study utilized the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database (2002-2019). We identified 4,107 patients newly diagnosed with gout who remained on continuous allopurinol therapy during the 24-month medication assessment period and matched them 1:3 with 12,321 non-gout controls using propensity score matching. Allopurinol adherence was assessed via the Medication Possession Ratio (MPR) over a 24-month period and categorized into three groups: MPR&#x2009;<&#x2009;0.3, 0.3&#x2009;&#x2264;&#x2009;MPR&#x2009;<&#x2009;0.8, and MPR&#x2009;&#x2265;&#x2009;0.8. Multivariable Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for fractures (vertebral, hip, and distal radius). RESULTS: Gout patients demonstrated a significantly higher risk of overall fractures compared to the non-gout group (aHR 5.52; 95% CI 4.19-7.26). A significant inverse linear relationship was observed between allopurinol adherence and fracture risk (P for trend&#x2009;<&#x2009;.001). The risk was highest in the low-adherence group (MPR&#x2009;<&#x2009;0.3; aHR 5.91; 95% CI 4.40-7.93) and relatively lower in the high-adherence group (MPR&#x2009;&#x2265;&#x2009;0.8; aHR 4.77; 95% CI 2.94-7.72). Consistent trends were observed for vertebral (aHR 5.68) and hip (aHR 4.22) fractures. These associations remained consistent across all subgroups, including age, sex, and comorbidities. CONCLUSION: Newly diagnosed gout is associated with a substantially increased risk of fractures. Higher adherence to Allopurinol therapy is correlated with a significant reduction in this risk, suggesting that consistent urate-lowering therapy may mitigate gout-related bone fragility. Key Points &#x2022; Newly diagnosed gout patients have a significantly higher risk of major osteoporotic fractures compared to the non-gout population. &#x2022; A significant inverse linear relationship exists between Allopurinol adherence and fracture risk, with the highest adherence group (MPR &#x2265; 0.8) showing a relatively lower risk. &#x2022; Consistent urate-lowering therapy (ULT) may mitigate bone fragility in gout patients by reducing systemic inflammatory burden caused by urate crystal deposition.

Humans