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Risk factors of venous thromboembolism in ICU patients: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to identify risk factors associated with the development of VTE in patients admitted to the intensive care unit (ICU). METHODS: A systematic literature search was conducted via PubMed, Embase, Web of Science, and Cochrane databases up to 25 April 2025, to identify studies examining the association between risk factors and the occurrence of venous thromboembolism (VTE) in ICU patients. Data were pooled using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 2465 relevant studies were identified through the systematic search, of which 30 were included in the meta-analysis. The pooled data showed that the following were significant risk factors for venous thromboembolism (VTE) in ICU patients: central venous catheterization (OR = 2.67, 95% CI: 1.67-4.28; I2 = 28%), invasive mechanical ventilation (OR = 2.08, 95% CI: 1.46-2.96; I2 = 0%), advanced age (OR = 2.06, 95% CI: 1.28-3.31; I2 = 86%), length of ICU stay (OR = 4.24, 95% CI: 1.43-12.57; I2 = 98%), malignancy (OR = 2.30, 95% CI: 1.03-5.12; I2 = 67%), elevated D-dimer levels (OR = 2.46, 95% CI: 1.37-4.40; I2 = 34%), and a history of VTE (OR = 2.84, 95% CI: 1.45-5.55; I2 = 51%). According to the GRADE assessment, the quality of evidence was rated as moderate for invasive mechanical ventilation, low for central venous catheterization and D-dimer levels, and very low for the remaining factors. CONCLUSION: Invasive mechanical ventilation, central venous catheterization, and elevated D-dimer levels are associated with VTE risk, supported by relatively high-quality evidence. These findings may help identify ICU patients at higher risk of VTE, inform the development of risk assessment models for patient stratification, and ultimately contribute to improved prognosis through optimal screening and management strategies.

Humans

Neuromodulation for Subjective Tinnitus: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: To evaluate the effectiveness and safety of neuromodulation and bimodal stimulation for chronic subjective tinnitus in randomized controlled trials (RCTs). DATA SOURCES: PubMed/MEDLINE, Web of Science, and EMBASE (January 2015-December 2025) searched per PRISMA 2020. REVIEW METHODS: Adult RCTs (≥ 18 years) with chronic subjective tinnitus (> 3 months) assessing validated outcomes (THI, TFI, TQ) for neuromodulation/bimodal interventions vs. sham/controls. Two-stage screening, Cochrane RoB-2 risk-of-bias assessment. Random-effects meta-analyses (REML) were performed when ≥ 3 comparable trials were available; effects reported as standardized mean differences (SMD) with 95% CIs. Main Outcomes and measures included change in tinnitus severity (THI/TFI/TQ) while secondary outcomes included loudness (VAS/NRS), durability, and adverse events. RESULTS: Twenty-six RCTs (n = 1576) met criteria: tES (11; n = 372), rTMS (8; n = 432), acoustic coordinated reset (1; n = 100), vagus nerve stimulation (2; n = 90), and bimodal stimulation (4; n = 582). Meta-analysis showed a nonsignificant pooled effect for tDCS (SMD -0.36; 95% CI -0.75 to 0.02; I 2 = 51%) and rTMS (SMD -0.15; 95% CI -0.37 to 0.07; I 2 = 0%). Single-trial evidence for coordinated reset showed no advantage over broadband noise. VNS demonstrated modest benefits with safety concerns limited to implanted approaches. Bimodal stimulation yielded consistent, clinically meaningful reductions (often ≥ 10-20 points on THI/TFI), with durability up to 12 months. Adverse events were mild/transient across noninvasive modalities. CONCLUSIONS: Noninvasive neuromodulation appears safe with average benefits; among modalities, bimodal stimulation shows the most consistent and durable clinical improvements. Standardized, adequately powered RCTs with harmonized protocols and long-term follow-up are needed to refine targets and dosing.

Humans

Air Pollution and Heat Impacts on Respiratory Morbidity and Mortality Outcomes in Africa: A Systematic Review Towards a Meta-analysis.

PURPOSE OF THE REVIEW: This review synthesised evidence on associations between air pollution and respiratory morbidity in Africa. Following PRISMA guidelines, we systematically searched PubMed, ScienceDirect and Elicit for case-control studies published between 2015 and 2025. RECENT FINDINGS: Thirteen studies from ten African countries reported pollutant levels far exceeding WHO guidelines. Indoor PM₂.₅ in biomass-using homes ranged from 96 to 177 µg/m³, and ambient PM₂.₅ reached 259 µg/m³. Nitrogen oxides were consistently associated with reduced lung function in children, while household air pollution increased risks of under-five mortality and low birthweight. Associations with acute respiratory infections varied across settings. Vulnerability was greatest among young children, those with airway hyperresponsiveness, and households with poor ventilation. Only three studies included temperature, and none examined heat-respiratory interactions. Across African case-control studies, particulate matter and household air pollution remain consistently linked to adverse respiratory outcomes, highlighting urgent needs for cleaner fuels, improved ventilation, and stronger evidence on combined pollution and heat exposures.

Humans

Respiratory effects of recruitment maneuvers according to lung recruitability assessed by electrical impedance tomography in patients with acute respiratory distress syndrome.

Recruitment maneuvers (RM) can improve oxygenation in patients with acute respiratory distress syndrome (ARDS), but their physiological effects depend on lung recruitability. This secondary analysis of a randomized controlled trial (RCT) evaluated oxygenation, respiratory mechanics, regional ventilation, and cardiorespiratory adverse events responses to a RM followed by electrical impedance tomography (EIT)-guided PEEP titration, using EIT to assess lung recruitability. In this study, fifty patients with moderate-to-severe ARDS underwent a stepwise RM followed by individualized PEEP titration guided by EIT. Lung recruitability was determined using the collapse index at PEEP 6 cmH&#x2082;O (CLPEEP6), defined as the proportion of collapsed lung at this PEEP level. Patients were classified into high- and low-recruitability groups based on median CLPEEP6 values. Oxygenation (PaO&#x2082;/FiO&#x2082;), static compliance (Cstat), driving pressure (Pdriv), regional ventilation distribution, and cardiorespiratory adverse events were compared before and after RM, during subsequent individualized EIT-guided PEEP titration. In patients with high recruitability (CLPEEP6&#x2009;>&#x2009;12.5), the PaO&#x2082;/FiO&#x2082; ratio and Cstat increased significantly after RM (PaO&#x2082;/FiO&#x2082;: 100.8&#x2009;&#xb1;&#x2009;30.3 vs. 125.4&#x2009;&#xb1;&#x2009;38.3&#xa0;mmHg, p&#x2009;<&#x2009;0.05; Cstat: 21.5&#x2009;&#xb1;&#x2009;5.8 vs. 28.0&#x2009;&#xb1;&#x2009;7.0&#xa0;mL/cmH&#x2082;O, p&#x2009;<&#x2009;0.001), Pdriv decreased (19.1&#x2009;&#xb1;&#x2009;3.5 vs. 15.6&#x2009;&#xb1;&#x2009;3.2 cmH&#x2082;O, p&#x2009;<&#x2009;0.001). EIT demonstrated a posterior redistribution of ventilation after RM. In contrast, patients with low recruitability (CLPEEP6&#x2009;&#x2264;&#x2009;12.5) showed no significant mechanical or oxygenation improvement and transient hypotension, arrhythmia, and desaturation appeared numerically more common in this group. No barotrauma or cardiac arrest occurred, and ICU mortality was similar between groups. A strategy combining a RM with subsequent individualized EIT-guided PEEP titration was associated with improved oxygenation and lung mechanics in patients with high lung recruitability, whereas patients with low recruitability showed limited physiological benefit, with cardiorespiratory adverse events appearing numerically more frequent. The EIT-derived CLPEEP6 index represents a feasible and clinically applicable https://clinicaltrials.gov/study/NCT06733168.

Humans

High-Flow Nasal Oxygen and the Risk of Gastric Insufflation: A Systematic Review and Meta-Analysis Supplemented by Narrative Synthesis.

High-flow nasal oxygen (HFNO) generates positive airway pressure, raising concerns about gastric insufflation and aspiration risk. Although most studies report minimal or no gastric distension, some suggest significant changes. This systematic review and meta-analysis applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to evaluate the effect of HFNO on gastric insufflation and related markers across clinical settings. We searched Medline, Embase, Emcare, and CINAHL through August 2025 for studies reporting qualitative or quantitative markers of gastric insufflation during HFNO use, including comet-tail artifacts, antral cross-sectional area, and gastric volume. Eligible designs included randomized trials, observational and volunteer studies, and case reports. Methodological quality was evaluated using the Mixed Methods Appraisal Tool, and certainty of evidence was rated with GRADE. Meta-analysis was performed for outcomes reported in two or more studies. Six randomized trials, five observational studies, two volunteer studies, one case series, and two case reports were included. Observational studies primarily assessed outcomes before and after HFNO intervention. Pooled analysis of four randomized controlled trials (RCTs; n = 375) showed HFNO significantly reduced gastric insufflation compared with face-mask ventilation during elective peri-intubation (risk ratios [RR] = 0.32; 95% confidence interval [CI], 0.19-0.52; P < .00001; I 2 = 0%), rated moderate-certainty. For antral cross-sectional area, pooled analysis of three RCTs (n = 318) found no significant difference between HFNO and face-mask ventilation (MD -0.33 cm 2 ; 95% CI, -0.72 to 0.05; P = .09; I 2 = 74%), rated moderate-certainty. Observational studies assessing pre- and post-HFNO changes showed no significant increase in antral cross-sectional area (MD 0.08 cm 2 ; 95% CI, -0.29 to 0.45; P = .67; I 2 = 0%) and no significant change in gastric liquid volume (MD -0.01 ml/kg; 95% CI, -0.07 to 0.06; P = .80; I 2 = 0%), both rated low certainty. Nonpooled data suggested possible increases in critically ill patients, but the evidence was of very low certainty. A single study assessing microaspiration found HFNO reduced gastroesophageal reflux and prevented microaspiration compared with face-mask ventilation. No clinically significant aspiration events were reported across studies. Moderate-certainty evidence supports HFNO as safe regarding gastric insufflation and antral cross-sectional area in most elective and procedural contexts. Low-certainty evidence suggests no increase in gastric volume. Caution is warranted due to limited, low-to-very-low-certainty evidence at higher flow rates and among critically ill patients. Larger multicenter trials and robust observational studies are necessary to confirm safety in these settings.

Humans

Diagnostic performance of intraoperative in vivo hyperspectral imaging for meningioma grading and molecular alterations: results from a prospective feasibility study.

OBJECTIVE: Hyperspectral imaging (HSI) is an emerging intraoperative, noninvasive, contrast agent-free imaging modality that enables quantitative assessment of tissue composition. The present study aimed to investigate whether HSI-derived tissue parameters correlate with WHO grade and molecular markers of aggressiveness in cranial meningiomas. METHODS: In this prospective study, intraoperative in vivo HSI was performed using the TIVITA tissue system, capturing spectral signatures between 500 and 1000 nm. Quantitative tissue parameters included tissue oxygen saturation (StO2), near-infrared perfusion index, organ hemoglobin index (OHI), and tissue water index (TWI). HSI parameters were correlated with histopathological WHO grade and molecular alterations, including CDKN2A/B deletion, TERT promoter mutation, and 1p/22q loss. Group differences were analyzed using one-way ANOVA, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. RESULTS: Forty-six meningiomas were included, comprising WHO grade 1 (n = 35) and WHO grade 2-3 (n = 11) tumors. TWI was significantly higher in WHO grade 2-3 meningiomas compared with WHO grade 1 tumors (mean 0.49 [SD 0.12] vs 0.38 [SD 0.17], p = 0.048). ROC analysis demonstrated an area under the ROC curve (AUC) of 0.71 (95% CI 0.56-0.86, p = 0.036) for TWI in discriminating higher-grade disease. A TWI cutoff &#x2265; 0.367 identified all WHO grade 2-3 meningiomas with 100% sensitivity and 100% negative predictive value. In a molecular subgroup (n = 15), OHI appeared higher in tumors with homozygous CDKN2A/B deletion than in nondeleted tumors (mean 0.77 [SD 0.04] vs 0.62 [SD 0.10]). However, only 3 CDKN2A/B-deleted cases were available, and these findings should be considered descriptive. ROC analysis yielded an AUC of 0.89 (95% CI 0.71-1.00). An OHI cutoff &#x2265; 0.712 identified all three CDKN2A/B-deleted tumors (100% sensitivity), with 83.3% specificity and 86.7% accuracy. CONCLUSIONS: The present investigation demonstrated that HSI-derived tissue water and hemoglobin metrics provide biologically meaningful information in meningiomas. Low tissue water content appeared to rule out higher-grade diseases in this first subset cohort, while elevated hemoglobin showed a potential association with CDKN2A/B deletion in a small exploratory subgroup. These findings support the potential of HSI as a real-time noninvasive tool for intraoperative risk stratification and should be evaluated in large-scale studies. German Clinical Trials Register no. DRKS00036771 (www.drks.de).

Humans

Comparison of deep and nondeep hypothermia in thoracic and thoracoabdominal aortic surgery: A systematic review and meta-analysis.

OBJECTIVE: Deep hypothermic circulatory arrest (DHCA) remains a cornerstone technique for neuroprotection and end-organ preservation during ascending aorta and arch surgeries. However, its benefits and risks compared with non-DHCA strategies in thoracic and thoracoabdominal aortic aneurysm (TAAA) repair are uncertain owing to conflicting evidence and variable institutional practices. METHODS: A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Cochrane guidelines. PubMed, Embase, and Cochrane Library were searched for comparative studies evaluating DHCA and non-DHCA techniques for open thoracic and TAAA repair. Random-effects models were applied to calculate pooled effect estimates. Effect sizes were risk ratio (RR) for binary end points and mean difference for continuous end points, both with 95% confidence intervals. Statistical significance was set at P < .05. Between-study heterogeneity was estimated using the I2 statistic. Metaregression analyses were used to explore the sources of heterogeneity. RESULTS: Nine observational studies, including 1041 patients, were analyzed. DHCA use was associated with a significantly lower risk of spinal cord injury (RR, 0.44; P = .012) compared with non-DHCA. However, DHCA was also associated with prolonged postoperative ventilation time (RR, 1.34; P = .003). No significant differences were observed in overall mortality, length of hospital and intensive care unit stay, stroke, or renal complications. Metaregression identified patient age as a moderator of length of stay variability, with older cohorts demonstrating longer recovery periods. CONCLUSIONS: DHCA is associated with a lower risk of spinal cord injury during TAAA repair without increasing mortality or stroke risk, although it is associated with longer ventilation times.

Humans

Comparison of Adult Tracheostomy Outcomes Before and After Implementation of a Dedicated Tracheostomy Team.

OBJECTIVE: (A) Determine patient and institutional factors associated with increased length of stay (LOS) and complications of tracheostomy, (B) Develop data-driven quality improvement in tracheostomy care. DESIGN: Mixed methods protocol used cross-sectional survey assessing institutional trends in tracheostomy-specific care. Retrospective chart review compared tracheostomy patient outcomes prior to and during implementation of a multidisciplinary tracheostomy care team and standardized guidelines. PARTICIPANTS: Patients undergoing tracheostomy from January 2019 to December 2021 at a tertiary hospital. METHODS: Patient factors, procedure type and indication, tracheostomy tube size, management timeline, insurance, and disease severity using Acute Physiology and Chronic Health Evaluation II (APACHE II) score were analyzed for associations with LOS and adverse events. Multivariate analyses controlled for APACHE II score and payer source. LOS and complications were compared between patients before and during implementation of multidisciplinary tracheostomy care team and standardized guidelines. RESULTS: Three-hundred and eighteen patients met criteria with a 21.7% complication rate, average LOS of 24 days (SD&#x2009;=&#x2009;28.523), and median LOS post-tracheostomy of 14 days (IQR 7, 29). Departments without standardized protocols had greater LOS (F[1,316]&#x2009;=&#x2009;28.706, P&#x2009;<&#x2009;.001]) and complication odds (OR&#x2009;=&#x2009;2.92, P&#x2009;=&#x2009;.015, 95% CI[1.231, 6.930]). Larger tracheostomy tube size was linked to increased LOS (&#x3b2;&#x2009;=&#x2009;.253, t(314)&#x2009;=&#x2009;4.741, P&#x2009;<&#x2009;.001, 95% CI[4.137, 10.081]). Delays from ventilation discontinuation to cuffless tube exchange and decannulation correlated with increased LOS (&#x3b2;&#x2009;=&#x2009;.406, t(184)&#x2009;=&#x2009;6.321, P&#x2009;<&#x2009;.001, 95% CI[.928, 1.771]); (&#x3b2;&#x2009;=&#x2009;.554, t(129)&#x2009;=&#x2009;7.625, P&#x2009;<&#x2009;.001, 95% CI[1.008, 1.715]). When focusing on a single department, comparing 2019 patients to 2021 patients (pre- and post-guideline and care team), overall, LOS decreased from 33.08 to 30.83 days (P&#x2009;=&#x2009;.586). When excluding patients discharged on a ventilator, the 2019 group had average LOS of 37.938 days versus 33.41 days in 2021 (P&#x2009;=&#x2009;.344). CONCLUSIONS: Standardized tracheostomy care guidelines and multidisciplinary care teams are critical to improving institutional outcomes. Data-driven approaches to quality improvement ensure efficient and targeted methods to improving patient care. LEVEL OF EVIDENCE: 4.

Humans

Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.

BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n&#xa0;=&#xa0;549) and a validation set (n&#xa0;=&#xa0;236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60&#xa0;mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60&#xa0;mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.

Humans

Diagnostic Value and Limitations of Dermoscopy in Humans and Animals: A Critical Comparative Analysis.

BACKGROUND: Dermoscopy is a noninvasive imaging technique that is well-established in human dermatology, where it enhances the diagnosis of neoplastic, inflammatory, infectious, and alopecic skin disorders. In veterinary dermatology, its use is expanding yet remains heterogeneous and largely descriptive, despite growing evidence of conserved dermoscopic patterns across species. HYPOTHESIS/OBJECTIVES: To review the applications of dermoscopy in veterinary dermatology, and to provide a comparative analysis of dermoscopic features observed in dogs, cats, and horses in relation to corresponding findings in human dermatology. MATERIALS AND METHODS: A systematic review of the literature reporting dermoscopic findings in veterinary dermatology was conducted in accordance with PRISMA guidelines. PubMed, Scopus and Google Scholar were searched for studies published up to 30 July 2025. Eligible studies included original articles describing dermoscopic features in dogs, cats, or horses. Extracted data included species, dermatological condition, dermoscopic findings, device type and histopathological correlation, when available. Levels of evidence were assessed using the Oxford Centre for Evidence-Based Medicine criteria. RESULTS: Thirty studies met the inclusion criteria. Most were descriptive case reports or case series. Dermoscopy was applied to a wide range of conditions, including alopecias, parasitic infestations, dermatophytosis, neoplastic and sebaceous lesions, inflammatory dermatoses, and congenital vascular anomalies. Recurrent dermoscopic features showed strong similarities to those described in human dermatology, although species-specific anatomical differences influenced interpretation. CONCLUSIONS: Dermoscopy represents a valuable adjunct diagnostic tool in veterinary dermatology, with clear translational relevance. Standardisation of terminology and further prospective studies are required to support its broader clinical integration.

Animals

Effect of transcutaneous auricular vagus nerve stimulation on postoperative pain in patients undergoing thoracoscopic partial lung resection: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Postoperative pain after thoracic surgery remains common and challenging. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique with potential analgesic effects. This study aimed to evaluate the efficacy and safety of taVNS for postoperative pain management in patients undergoing thoracoscopic partial lung resection. METHODS: Adults undergoing thoracoscopic partial lung resection were randomized to active or sham taVNS. The primary outcome was cough pain intensity at 48h post-surgery, assessed by Numeric Rating Scale (NRS). Secondary outcomes included cough pain at 24h and 72h, resting pain, moderate-to-severe pain incidence,&#xa0;opioid consumption, quality of recovery, postoperative pulmonary complications , chest tube duration, hospital stay, postoperative nausea/vomiting, and adverse events. RESULTS: Among 119 analyzed patients (active n&#x2009;=&#x2009;60, sham n&#x2009;=&#x2009;59), active taVNS reduced cough pain scores at 24h, 48h, and 72h postoperatively, as well as resting pain (p < 0.05). It also lowered the incidence of moderate-to-severe cough pain at 24h and 48h, reduced cumulative postoperative opioid use at 24h and 72h, and decreased rescue analgesia on postoperative day 3 (p < 0.05). Active taVNS was associated with a lower incidence of postoperative pneumothorax (p < 0.05). No serious adverse events occurred. CONCLUSION: Perioperative taVNS was associated with a modest analgesic benefit and reduced postoperative opioid requirements after thoracoscopic partial lung resection. The observed reduction in postoperative pneumothorax requires cautious interpretation, and further multicenter trials are needed to determine its clinical utility.

Humans

Changes in ACL T2* Metrics Over the Course of the Female Menstrual Cycle: A New Biomarker for the ACL Injury Risk?

BACKGROUND: Sex-based disparities in the anterior cruciate ligament (ACL) injury risk may be partly explained by cyclic variations in sex hormones that drive systemic shifts in tissue osmoregulation. Ultrashort echo time (UTE) T2* magnetic resonance imaging provides a noninvasive, quantitative means of evaluating the water content and collagen orientation in tissue. HYPOTHESIS: Eumenorrheic female participants will exhibit significant ACL T2* changes across the cycle, while anovulatory control participants will demonstrate no significant changes over time. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 25 women with no prior knee injuries were enrolled: 10 premenopausal, eumenorrheic participants and 15 anovulatory control participants (6 postmenopausal and 9 premenopausal using oral contraceptives). Bilateral knee magnetic resonance imaging was performed at 4 time points evenly spaced over 1 month, with the first visit within 24 hours of menses onset. Ovulation status was confirmed using commercially available ovulation predictor kits. Three-dimensional UTE sequences (11 echoes; 0.03-25 ms) were acquired to evaluate bicomponent ACL T2* metrics. Linear mixed-effects models assessed temporal differences in long and short T2* values, and the Cohen d quantified effect size. RESULTS: Eumenorrheic participants demonstrated significantly shorter preovulatory long T2* values compared with postovulatory values (mean difference, 1.0 ms [95% CI, 0.2-1.9 ms]; P = .015; Cohen d = 0.51). No significant temporal differences were observed for any T2* metric in anovulatory controls. CONCLUSION: Eumenorrheic female participants exhibited significant preovulatory to postovulatory changes in ACL T2* metrics, while anovulatory controls demonstrated no significant changes over time. These findings suggest that ACL T2* metrics are sensitive to cyclic fluctuations in female sex hormones across the menstrual cycle.

Humans

Repetitive transcranial magnetic stimulation in substance use disorders is safe and tolerable: A Systematic review of 141 clinical trials including 4299 participants.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation intervention investigated as a treatment for substance use disorder (SUD) and its co-occurring disorders. As the number of rTMS SUD clinical trials increase, the safety and tolerability profile should be assessed. In this systematic review, we investigate adverse events (AEs) of rTMS in individuals with SUD and factors that may influence their occurrence. METHODS: We performed a systematic PubMed search to identify all controlled trials of rTMS in SUD published up to January 2025. Eligible studies were assessed, and safety information was extracted for analysis. RESULTS: A total of 141 clinical trials with 4299 participants were included in their active arms. rTMS trials recruited participants who were engaged in active substance use, were in the pre-treatment phase, in early recovery, or in sustained recovery. Twenty-two studies explicitly reported no AEs. Sixty-nine studies reported only mild AEs, while only six studies reported moderate AEs. Thirty-five studies did not report safety-outcomes/AEs. As expected, participants reported mild and temporary AEs such as headaches, pain or discomfort under the coil, or dizziness. Only nine studies reported serious AEs (7 studies in active TMS and 2 in sham TMS). Importantly, no seizures attributable to active rTMS were reported in these SUD samples. CONCLUSION: Overall, rTMS in SUD samples is safe and well-tolerated regardless of recovery stage and substance. Most reported side effects were mild, self-limiting, and tolerable. However, AE reporting was incomplete, as 35 of 141 trials reported no safety data, limiting conclusions to reported outcomes. This evidence supports the safety of rTMS as a potential stand-alone or adjunctive treatment for SUD.

Humans

Effect of intraoperative 40-hz gamma-frequency auditory stimulation on postoperative delirium in older adults undergoing major surgery: a randomized clinical trial protocol.

INTRODUCTION: Postoperative delirium (POD) is a common and clinically significant complication among older adults undergoing major surgery under general anesthesia. Gamma-frequency (40-Hz) auditory stimulation has demonstrated potential neuroprotective and cognition-enhancing effects, suggesting a plausible role in perioperative delirium prevention. However, direct clinical evidence supporting intraoperative 40-Hz auditory stimulation in reducing POD remains limited, warranting rigorous evaluation in a randomized trial. PATIENTS AND METHODS: This prospective, parallel-group, randomized controlled trial will enroll 550 older adults scheduled for major noncardiac, nonneurosurgical surgery under general anesthesia. Participants will be randomized in a 1:1 ratio to either the active stimulation group, receiving intraoperative 40-Hz gamma-frequency auditory stimulation delivered via headphones for 2&#x2009;h following successful anesthesia induction, or the sham stimulation group, wearing headphones without active auditory output. The primary outcome is the incidence of POD on postoperative day 1 though 3, assessed using the Confusion Assessment Method (CAM) or the CAM for the ICU (CAM-ICU). Secondary outcomes include POD severity, sleep quality, pain scores, analgesic consumption, the incidence of postoperative nausea and vomiting (PONV), rescue antiemetic use, duration of post-anesthesia care unit (PACU) stay, length of hospital stay, quality of postoperative recovery, incidence of perioperative adverse events; postoperative morbidity, health-related quality of life, and all-cause 30-day mortality. DISCUSSION: This trial will determine whether intraoperative 40-Hz gamma-frequency auditory stimulation reduces the incidence of POD among older adults undergoing major surgery under general anesthesia. If efficacious, this noninvasive intervention could constitute a feasible perioperative strategy to mitigate delirium risk and enhance postoperative recovery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500115156).

Humans

Teaching Engagement and Caregiving Help in the Intensive Care Unit (TEACH-ICU) Scale: Content Validity.

BACKGROUND: Having family members provide care to their loved ones in the intensive care unit (ICU) is a beneficial yet seldom implemented approach. For family members to perform caregiving, nurses must be willing to teach, and such willingness is a developing area of research. OBJECTIVES: To adapt an instrument validated in family members, the Family Willingness for Caregiving Scale, to address nurses' willingness to teach family members caregiving skills. METHODS: Purposive and snowball sampling were used to recruit 10 expert ICU nurses through the American Association of Critical-Care Nurses' research website and social media platforms. The researchers conducted cognitive interviews with the nurses to address the instrument's content validity. RESULTS: The scale was refined based on the participants' feedback. Items were deleted, added, and revised. Furthermore, scale instructions were adjusted to emphasize the willingness to teach families of patients receiving mechanical ventilation. Qualitative themes emerged related to barriers to family engagement, including time constraints, patient acuity, and nurse and family characteristics. CONCLUSIONS: Content validity of the scale was assessed, with future research aimed at pilot testing and evaluating construct validity before using the scale as a research instrument. Practical implications include using the scale as an evaluation tool to determine nurses' willingness to teach family members about caregiving. After evaluation, various strategies could be incorporated to enhance family engagement in adult ICUs.

Humans

Effects of Transcranial Direct Current Stimulation and Individualized Physical Therapy on Pain and Function in Individuals With Chronic Knee Pain: A Pilot Study.

BACKGROUND AND PURPOSE: Noninvasive brain stimulation is a promising neuromodulatory intervention for chronic pain. This study aimed to determine the impact that transcranial direct current stimulation (tDCS) in combination with individualized physical therapy (PT) has on pain and function in individuals with chronic knee pain. METHODS: This study was a preliminary pragmatic, triple-blinded, randomized, and sham-controlled clinical trial performed in an outpatient orthopedic physical therapy clinic. Participants participated in 5 sessions of active or sham tDCS followed by individualized PT intervention. Pain outcomes included the Numeric Pain Rating Scale, Movement-Evoked Pain, pressure pain thresholds (PPT), and the Central Sensitization Inventory. Functional outcomes included the 2-minute walk test, 5-time sit-to-stand test, quadriceps strength, knee range of motion, Patient Specific Functional Scale, and the Lower Extremity Functional Scale. RESULTS: Thirty participants with chronic knee pain completed the study. There were no significant differences observed for primary patient-centered pain and functional outcomes. For secondary outcomes, the active tDCS group had a significant effect (p&#xa0;<&#xa0;0.05) on percent change in lateral joint line PPT and a significant multivariate effect of group on PPT change scores for 3-site and 5-site clusters (p&#xa0;<&#xa0;0.05). Exploratory responder analyses demonstrated that the active tDCS group was 12.8 times more likely to achieve the minimum detectable change in quadriceps strength improvement compared with the sham tDCS group (p&#xa0;<&#xa0;0.05). DISCUSSION: There were no significant between-group differences for primary pain and functional outcomes. However, the active tDCS group showed improvements in pain sensitivity, as measured by PPT, and quadriceps strength, which were superior to those seen in the sham tDCS group. These preliminary findings provide insight into possible mechanisms of tDCS in addressing pain as opposed to efficacy. Given that there were no clear between-group differences in patient-centered outcomes, there is insufficient evidence for routine tDCS use for chronic knee pain. TRIAL REGISTRATION: NCT06132412.

Humans

Clinical Utility of Ultra-Widefield Swept-Source OCT for Intraocular Tumors: Comparison With Ultrasonography, SD-OCT, and MRI.

PURPOSE: To evaluate the clinical performance of ultra-widefield swept-source optical coherence tomography (UWF-OCT) in the assessment of choroidal tumors and to compare it with ultrasonography (US), spectral-domain (SD)-OCT, and magnetic resonance imaging (MRI). DESIGN: Retrospective diagnostic comparison. SUBJECTS: Thirty-nine eyes from 39 patients diagnosed with choroidal tumors at a single tertiary referral center. METHODS: This retrospective diagnostic comparison evaluated patients diagnosed with choroidal tumors at a single tertiary referral center between January 2023 and August 2025. All patients underwent UWF-OCT imaging at diagnosis. Tumor measurements obtained with UWF-OCT were compared with US, SD-OCT, and MRI. Comparative analysis among imaging modalities and predictors affecting UWF-OCT applicability was performed. MAIN OUTCOME MEASURES: Tumor thickness (mm) and largest basal diameter (LBD, mm) measurements, and complete measurability rate across different tumor size categories. RESULTS: Thirty-nine eyes from 39 patients (mean age 59.2 &#xb1; 16.9 years) were analyzed, including 27 choroidal melanomas (69.2%), 5 metastatic tumors (12.8%), 4 hemangiomas (10.3%), 2 osteomas (5.1%), and 1 (2.6%) indeterminate choroidal melanocytic lesion. UWF-OCT successfully measured both tumor thickness and largest basal diameter (LBD) in 100% (31/31) of small and medium choroidal tumors, substantially outperforming SD-OCT (complete measurement achieved in 63.6% of small tumors, and 0% of medium or large tumors). UWF-OCT measurements were systematically smaller than ultrasonography (thickness: -32.3%, P < .01; LBD: -11.1%, P < .01) and MRI (thickness: -29.2%, P < .01). Mushroom-shaped tumor morphology was the strongest negative predictor of UWF-OCT quality (OR = 0.015, 95% CI 0.001-0.196, P < .01). UWF-OCT's complete measurability was limited in large tumors (12.5%, 1/8). CONCLUSIONS: UWF-OCT provides precise, noninvasive, single-scan assessment of small-to-medium choroidal tumors with detailed structural visualization. It may be particularly useful for dome-shaped tumors, while multimodal imaging with US and MRI remains optimal for complex morphologies. Overall, UWF-OCT represents a valuable tool for diagnosis and treatment planning, with potential utility for longitudinal follow-up in choroidal tumor management.

Humans

Effects of cold-water immersion after rugby-specific training on endurance performance.

BACKGROUND: This study investigated whether whole-body cold-water immersion (CWI) following rugby-specific training influences endurance exercise performance 24 h later. METHODS: Eleven healthy male collegiate rugby players completed an incremental cycling test to determine peak oxygen uptake (V&#x307;O 2peak ) and time to exhaustion at baseline (Pre). One week later, participants performed a standardized rugby-specific training session consisting of warm-up, skill-based passing, contact drills, individual training (i.e., conversion kicking and scrummaging), and a bronco endurance test (total duration: 180 min), followed by one of two recovery interventions in a randomized order: 1) whole-body CWI for 8 min at 15 &#xb0;C (CWI) or 2) seated rest for 8 min (Control). Participants then performed the incremental cycling test 24 h after each intervention. RESULTS: Training load during the rugby-specific training, assessed using heart rate-based training load and blood lactate concentrations, did not differ between the trials. Time to exhaustion (485&#xb1;72 vs. 518&#xb1;77 s, P=0.107, d=0.45) and V&#x307;O 2peak did not differ between the Control and CWI trials, whereas the relative changes in these variables from Pre were greater in the CWI than in the Control trials (both P<0.05). Oxygen uptake, minute ventilation, and rating of perceived exertion during submaximal exercise were similar across the Pre, Control, and CWI trials. CONCLUSIONS: These results suggest that whole-body CWI following rugby-specific training may be associated with favorable changes in endurance exercise performance 24 h post-intervention compared with the control condition. However, the expectancy/placebo effect of water immersion on exercise performance could not be excluded.

Humans