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Effect of brewers' yeast or beta-glucan derived from Saccharomyces cerevisiae on breast milk supply following preterm birth: the BLOOM randomised controlled trial.

OBJECTIVE: Breast milk is the optimal source of nutrition for preterm infants; however, low breast milk production is common following a preterm birth. This study aimed to determine if taking brewers' yeast or beta-glucan improves daily expressed breast milk volume. DESIGN: Randomised, blinded, parallel, placebo-controlled trial. SETTING: Three Australian tertiary-level neonatal units. PATIENTS: Mothers with a singleton or twin pregnancy who gave birth at <34 weeks' gestation. INTERVENTIONS: Mothers were randomised within 72 hours of birth into three parallel groups in a 1:1:1 ratio to receive either brewers' yeast, beta-glucan or placebo capsules for 7&#x2009;days. MAIN OUTCOME MEASURE: Total expressed breast milk volume over a 24-hour period on day 7 of intervention. RESULTS: A total of 105 mothers underwent randomisation between August 2022 and April 2024 (36 brewers' yeast, 35 beta-glucan and 34 placebo). The adjusted mean difference in daily expressed breast milk volume was 94&#x2009;mL/day (95%&#x2009;CI -51 mL/day to 239&#x2009;mL/day) between the brewers' yeast and placebo groups and -25&#x2009;mL/day (95%&#x2009;CI -173 mL/day to 123&#x2009;mL/day) between the beta-glucan and placebo groups. Maternal side effects were similar across groups. CONCLUSION: We found no clear effect of short-term administration of brewers' yeast or beta-glucan on breast-milk production following preterm birth; both interventions were well tolerated. Given the small sample size, these findings do not rule out the possibility of a clinically meaningful benefit of brewers' yeast and suggest further research with a larger sample size may be warranted to clarify the potential clinical impact. TRIAL REGISTRATION NUMBER: ACTRN12622000968774.

Intensive Care Units, Neonatal

Donor Human Milk Utilization in a Level 1 Newborn Unit of a High-Volume Delivery Hospital: A Cautionary Tale.

INTRODUCTION: Donor human milk (DHM) is an alternative to formula for supplementation of breastfed newborns and has been associated with higher in-hospital exclusive breast milk feeding rates. Its use has increased substantially, most recently among term newborns, yet there is scarce data to describe patient characteristics and volumes administered. We aimed to characterize DHM utilization in our level 1 nursery. METHODS: We conducted a retrospective cross-sectional study of newborns discharged in 2022 from the level 1 nursery. Variables included sex, gestational age, birth weight, delivery type, hypoglycemia diagnosis, DHM volume, and length of stay. DHM use was compared across preferred language, race, ethnicity, and payer type using chi-square testing. RESULTS: A total of 10,432 discharges were reviewed-those transferred to Neonatal Intensive Care Unit (NICU) or another unit were excluded. Of 9,074 newborns receiving level 1 care, 1,094 (12.1%) received DHM. Newborns born between 35 and 37 weeks gestation, delivered by cesarean section, or diagnosed with hypoglycemia or small for gestational age were more likely to receive DHM (p < 0.05). DHM was also more common among newborns whose birth parent preferred the English language, identified as White or non-Hispanic, or had non-Medicaid insurance (p < 0.05). 6,552.6 ounces were consumed, with a total median of 3.9 ounces per newborn (dose range 2-50 mL). CONCLUSIONS: DHM use in the level 1 nursery varied by clinical and sociodemographic factors, revealing inequities. In addition, some doses exceeded recommended supplemental volumes. Future efforts should focus on ensuring equitable access to DHM, standardized dosing and discontinuation guidelines, and evaluation of impacts on exclusive breastfeeding rates.

Humans

Efficacy and Safety of Celecoxib Combined With Jintiange Capsules for the Treatment of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND Knee osteoarthritis (KOA) poses a substantial global health burden, and conventional nonsteroidal anti-inflammatory drug (NSAID) therapy with celecoxib is hindered by adverse effects. This study evaluated the efficacy and safety of combining celecoxib with Jintiange capsules, a synthetic tiger bone formulation used in traditional Chinese medicine (TCM), to manage symptomatic KOA. MATERIAL AND METHODS This 12-week, randomized, double-blind, placebo-controlled trial enrolled 120 patients with KOA (age &#xf0b3;40 years; visual analog scale [VAS] score 4-7). Participants received celecoxib (200 mg/day tapered to 100 mg/day) combined with either Jintiange capsules (3.6 g/day) or placebo. The primary outcome was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. Secondary outcomes included WOMAC subscale scores (pain, function, and stiffness), VAS scores, and adverse drug reaction reports. RESULTS The experimental group demonstrated a 23.5-point (37.8%) reduction in WOMAC total score from baseline (P<0.001); the control group showed a 13.2-point (21.6%) reduction (P<0.001). The experimental group achieved 51.6% improvement in the WOMAC pain subscale (P<0.001), whereas the control group showed 33.3% improvement (P<0.001). Relative to the control group, the experimental group demonstrated a greater reduction in VAS score (P<0.001). Combined TCM-NSAID therapy produced significantly greater pain relief and functional improvement than NSAID monotherapy. CONCLUSIONS Celecoxib combined with Jintiange capsules provided clinically meaningful improvements in pain relief and functional outcomes relative to celecoxib monotherapy in patients with KOA. These findings support integration of TCM with conventional pharmacotherapy for osteoarthritis management.

Humans

Pharmacokinetic and Pharmacodynamic Bio-Similarity of ADL-018 to Innovator Omalizumab: A Randomized Study in Healthy Adults.

Bioequivalence and safety of ADL-018, an omalizumab biosimilar, were compared with United States-licensed omalizumab (US-OMA) and European Union-approved omalizumab (EU-OMA), both approved for allergies. Healthy adults were randomized (1:1:1) to receive a dose of ADL-018, US-OMA, or EU-OMA (150 mg/mL). Pharmacokinetic (PK) parameters, including AUC(0-last), AUC(0-&#x221e;), and Cmax, were considered equivalent if 90% CIs of geometric mean ratios (GMRs) were within predefined equivalence margin (0.80-1.25) using ANCOVA model. Other PK parameters, pharmacodynamics (PD) (free/total immunoglobulin E [IgE]), immunogenicity, and safety were compared. Overall, 306 participants (n&#xa0;=&#xa0;102 per arm) were dosed; 287 completed the study. Equivalence of primary PK parameters was confirmed for pairwise comparisons, with 90% CIs within the predefined margin (GMRs of ADL-018 vs US-OMA: AUC(0-last)-1.08, AUC(0-&#x221e;)-1.07, Cmax-1.05; GMRs of ADL-018 vs EU-OMA: AUC(0-last)-1.06, AUC(0-&#x221e;)-1.06, Cmax - 1.05; and GMRs of US-OMA vs EU-OMA: AUC(0-last)-0.99, AUC(0-&#x221e;)-0.99, Cmax-1.00). PK/PD parameters were comparable across arms. Increase in total IgE (AUEC &#x223c;30,000 to 35,000 h IU/mL) and decrease in free IgE (AUEC &#x223c;29,000 to 35,000 h IU/mL) were comparable across arms. Similar incidence of adverse events across arms (treatment-emergent adverse events: ADL-018, n&#xa0;=&#xa0;6; US-OMA, n&#xa0;=&#xa0;5; EU-OMA, n&#xa0;=&#xa0;4) was observed. ADL-018 demonstrated PK/PD equivalence and comparable safety profile to reference omalizumab.

Humans

The Efficacy of Erector Spinae Plane Block Versus Subcostal Transversus Abdominis Plane Block in Laparoscopic Nephrectomy: A Randomized Clinical Trial.

OBJECTIVES: This study compared the efficacy and safety of erector spinae plane block (ESPB) versus subcostal transversus abdominis plane (TAP) block in reducing postoperative pain among patients undergoing laparoscopic nephrectomy. METHODS: This randomized clinical trial enrolled 70 adult patients, ASA physical status I or II, who underwent total (radical) laparoscopic nephrectomy under general anesthesia. Patients were randomly assigned to 2 groups. Group ESPB received an ultrasound-guided ESPB at the T7 transverse process level, while group TAP received an ultrasound-guided subcostal TAP block. The primary outcome was the total amount of morphine consumed at 6 and 24 hours postoperatively. Secondary outcomes included the incidence of patients requiring opioid analgesia, time to rescue analgesia, visual analog scale of pain intensity, time to postoperative ambulation, intraoperative and postoperative hemodynamics, arterial partial pressure of oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 or P /F) ratio, and incidence of complications. RESULTS: Compared with the TAP group, the ESPB group exhibited significantly lower median morphine consumption at 24 hours ( P =0.032), prolonged time to first analgesic rescue ( P =0.049), and lower incidence of rescue morphine requirement (OR=0.23; 95% CI=0.06-0.94; P =0.031), with lower visual analog scale pain scores at 12, 18, and 24 hours postoperatively ( P <0.001). The mean arterial blood pressure and heart rates were comparable between groups. No significant adverse effects from either approach. DISCUSSION: In laparoscopic nephrectomy, ultrasound-guided ESPB may safely and effectively be used to improve pain management and reduce pain intensity, with stable hemodynamics and a comparable risk of postoperative complications to the ultrasound-guided subcostal TAP block.

Humans

Theta-range SEEG stimulation for intracranial mapping: extending conventional 1-Hz and 50-Hz protocols.

OBJECTIVE: Electrical brain stimulations (EBS) are central to epileptic network identification and functional mapping during stereo-electroencephalography, yet stimulation frequencies remain empirical, and standardized across patients and brain regions, producing false negatives and false positives, and potentially compromising surgical outcome. We prospectively investigated theta-range EBS (7&#xa0;Hz) in the temporal lobe, a prominent physiological frequency band in this region, and compared it with conventional 1-Hz and 50-Hz protocols. METHODS: We analyzed 1,408 temporal EBS in 25 drug-resistant epileptic patients. Epileptic responses (afterdischarges, seizures) and clinical signs were assessed across the epileptic network and temporal structures (amygdala, hippocampus, neocortex, parahippocampal gyrus, white matter), and confronted to stimulation parameters (frequency, intensity, duration, total charge). RESULTS: At matched intensity and duration, 7-Hz EBS were associated with a higher occurrence of afterdischarges and clinical signs than 1-Hz EBS in several temporal structures. Effects on usual seizure induction were less consistent. Comparisons with 50&#xa0;Hz showed no systematic significant differences, with responses observed at one or both frequencies depending on structure and outcome. When controlling for total charge, frequency-related differences were attenuated. Some effects were sporadically observed at both intermediate frequency and charge quantity. CONCLUSIONS: EBS responses emerge from the interaction between all electrical parameters and anatomical location and local excitability, and can hardly be disentangled. However, 7-Hz EBS can provide complementary clinical information during temporal-lobe mapping, with a targeted approach. SIGNIFICANCE: These findings support targeted evaluation of broader stimulation parameter spaces, including intermediate frequencies, rather than routine reliance on fixed low- and high-frequency protocols alone.

Humans

Trends in the Prevalence of Foods High in Saturated Fats, Sodium, and Added Sugars among U.S. adults, NHANES 2007-2018.

BACKGROUND: Foods and beverages high in saturated fats, sodium, and added sugars (HFSS) are often ultra-processed and linked to poor health outcomes, but few studies have investigated their intake. OBJECTIVE: To describe the trends in the intake of HFSS foods and beverages between 2007 and 2018 in a nationally representative sample of U.S. adults, by sociodemographic characteristics and What We Eat in America food groups. DESIGN: This is a secondary, cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. PARTICIPANTS/SETTING: The final sample included 27,984 adults 19 years of age or older from NHANES with at least one complete dietary recall. MAIN OUTCOME MEASURES: The primary outcomes are the percentage of total energy intake from foods classified as HFSS according to the Pan American Health Organization (PAHO) Nutrient Profile Model. STATISTICAL ANALYSES PERFORMED: To estimate the percentage of energy intake from foods and beverages HFSS, linear regression models with interaction terms between cycles and covariates were used. RESULTS: The overall intake of foods and beverages HFSS did not change, representing over 60% of the total energy intake between 2007-2010 and 2015-2018. The intake of foods and beverages high in sodium increased by 2.0 percentage points (95% CI: 0.5, 3.5) and 3.5 percentage points (95% CI: 1.1, 5.8), respectively. The intake of foods and beverages high in saturated fats increased by 6.1 percentage points (95% CI: 4.5, 7.6) and 6.1 percentage points (95% CI: 3.9, 8.2), respectively. The intake of foods and beverages high in added sugars did not change. CONCLUSION: In the U.S., intake of HFSS foods and beverages is high. Future research should focus on whether public health interventions and policies might reduce the intake of foods high in nutrients of concern.

Added sugars

Hyperbaric oxygen for the treatment of traumatic incomplete spinal cord injury: a systematic review and meta-analysis of randomized controlled trials.

The therapeutic efficacy of hyperbaric oxygen therapy for traumatic incomplete spinal cord injury remains a subject of debate. To comprehensively evaluate the impact of hyperbaric oxygen on motor function, sensory function, and activities of daily living in patients with traumatic incomplete spinal cord injury, we conducted a systematic review and meta-analysis. We performed a comprehensive search across PubMed, Embase, the Cochrane Library, Web of Science, and major Chinese databases for randomized controlled trials published through June 2025. A total of 15 randomized controlled trials were included. The pooled results indicated that hyperbaric oxygen therapy significantly improved the American Spinal Injury Association motor score (mean difference = 10.30, 95% confidence interval: 7.70-12.90), the total American Spinal Injury Association sensory score (mean difference = 29.29, 95% confidence interval: 18.82-39.75), the American Spinal Injury Association light touch score (mean difference = 9.84, 95% confidence interval: 6.15-13.53), and the American Spinal Injury Association pinprick score (mean difference = 8.75, 95% confidence interval: 4.40-13.11). Furthermore, hyperbaric oxygen therapy was associated with significant enhancements in the Barthel Index (mean difference = 16.60, 95% confidence interval: 10.51-22.68) and the Functional Independence Measure (mean difference = 17.41, 95% confidence interval: 10.83-23.98). In conclusion, adjunctive hyperbaric oxygen therapy appears to improve motor function, sensory function, and activities of daily living in patients with traumatic incomplete spinal cord injury compared to conventional treatments alone. However, due to methodological limitations and potential publication bias in the included studies, these findings should be interpreted with caution, and further high-quality, multi-center randomized controlled trials are warranted.

Humans

Comparative safety of lipid-lowering drugs alone or in combination: insights from a systematic review and network meta-analysis.

BACKGROUND AND AIMS: Although the safety profile of lipid-lowering therapies (LLTs) is known, there are no comprehensive comparative assessments. We aimed to compare the risk of muscle-related events, diabetes, liver dysfunction, and cognitive disorders among LLTs through a network meta-analysis. METHODS AND RESULTS: Databases were searched from inception to May 2025. Eligible studies included adult patients, using statins, ezetimibe, PCSK9 monoclonal antibodies (PCSK9mAbs), inclisiran, bempedoic acid, or their combinations as intervention, reporting the information about any of the selected adverse events, a total sample size of &#x2265;200 subjects, and had &#x2265;1 month of intervention. Pooled estimates were assessed by fixed effects model within a frequentist setting. Pooled relative risks (RR) and their 95% confidence interval were estimated. A total of 303,397 subjects from 153 RCTs were included. Bempedoic acid ranked the lowest risk of myalgia (vs PCSK9mAbs, RR 0.80 [0.69, 0.93]). PCSK9mAbs were associated with lower incidence of creatine kinase (CK) elevation, diabetes, and liver dysfunction comparing to statins (statins vs PCSK9mAbs, RR 1.44 [1.14, 1.81], RR 1.13 [1.05, 1.22], and RR 1.38 [1.17, 1.62], respectively). In terms of muscle-related events and cognitive disorders, no significant risk differences were found among treatments and their combinations. CONCLUSIONS: PCSK9mAbs appear to have a more favourable safety profile regarding the risk of CK elevation, diabetes, and liver dysfunction. Bempedoic acid seem to be a better choice for subjects with high risk of myalgia. This information can be valuable when selecting therapy for specific patient subgroups at higher risk of certain adverse events.

Humans

Dietary approaches for glycemic management in type 1 diabetes: A systematic review of Mediterranean and low-carbohydrate diets.

BACKGROUND/OBJECTIVES: Specific dietary approaches for better management of type 1 diabetes (T1D) have not been thoroughly investigated. We conducted a systematic review to evaluate the Mediterranean and low-carbohydrate diets for glycemic management in people with T1D. METHODS: We examined longitudinal studies (cohort studies and clinical trials) including individuals with T1D who followed low-carbohydrate diets (<26% calories from carbohydrates and/or <130&#x202f;g of carbohydrates per day) and/or a Mediterranean diet, while hemoglobin A1c (HbA1c) and/or time in range (TIR) were measured. Additional eligibility criteria included publication in English and availability of a full-text primary research article. Non-longitudinal studies, abstracts, and studies published in languages other than English were excluded. Results were synthesized narratively, and the GRADEpro Guideline Development Tool was used to assess article quality. RESULTS: A total of 565 studies were identified from PubMed, the Web of Science, and citation chasing. After removal of duplicates and further evaluation, 22 studies (6 cohort studies and 16 clinical trials; total n&#x202f;=&#x202f;3284) were included in this review. The search was initially completed in May 2024, and updated February 2026. Low-carbohydrate diets were associated with better glycemic management when compared to usual diets or baseline glycemic parameters. Studies using CGM were overall underpowered. The impact of Mediterranean diets was less clear, but generally appeared to be less effective at improving glycemic management than low-carbohydrate diets. DISCUSSION: Although structured dietary interventions for T1D hold promise for improving glycemic outcomes, further research is needed to determine exactly which dietary intervention is most beneficial for this population. The evidence provided by included studies is limited by small sample sizes and short durations; better powered, longer-term studies are required to inform clinical recommendations.

Humans

Intravenous Tranexamic Acid Reduces Perioperative Blood Loss in Reduction Mammoplasty With Immediate Implant-Based Reconstruction: A Randomized, Triple-Blinded, Placebo-Controlled Trial.

BACKGROUND: Postoperative hematoma and oozing can compromise outcomes after reduction mammoplasty with immediate reconstruction. Intravenous (IV) tranexamic acid (TXA) is antifibrinolytic, but prospective evidence in this setting is limited. OBJECTIVES: The aim of this study was to determine whether a single pre-incision dose of IV TXA reduces perioperative blood loss and fibrinolytic activation vs placebo. METHODS: In this randomized, triple-blinded, placebo-controlled trial, 60 women (American Society of Anesthesiologists I/II, 18-75 years) undergoing bilateral reduction mammoplasty with immediate implant-based reconstruction received TXA 10&#x2005;mg/kg in 100&#x2005;mL saline or placebo 10&#x2005;min before incision. The primary outcome was total blood loss within 24&#x2005;h (intraoperative suction + swab plus drain output). Secondary outcomes were perioperative changes in hemoglobin, D-dimer and fibrinogen, and complications within 30 days. Intention-to-treat analyses were performed. RESULTS: All patients completed follow-up. Total blood loss was lower with TXA than with placebo (mean &#xb1; standard deviation: 221.1 &#xb1; 72.4 vs 298.1 &#xb1; 90.6&#x2005;mL; mean difference -77.0&#x2005;mL; 95% CI, -122.4 to -31.6; P = .001). Intraoperative loss and 24&#x2005;h drain output were also reduced. Postoperative D-dimer rise was attenuated with TXA (0.31 &#xb1; 0.15 vs 0.49 &#xb1; 0.22&#x2005;&#xb5;g/mL; P = .002); hemoglobin decline was smaller. No thromboembolic, neurologic, or allergic events occurred; no skin-flap necrosis was observed. CONCLUSIONS: Pre-incisional IV TXA safely reduces perioperative bleeding and fibrinolytic activity after reduction mammoplasty. These findings support incorporation of IV TXA into perioperative protocols. LEVEL OF EVIDENCE: 2 (THERAPEUTIC): For image description, please refer to the figure legend and surrounding text.

Humans

Comparison of long-term outcomes between liver transplantation and liver resection for intrahepatic cholangiocarcinoma: An updated systematic review and meta-analysis.

BACKGROUND: Liver resection (LR) has been the standard treatment for intrahepatic cholangiocarcinoma (ICC), but is associated with high recurrence rates and poor prognosis. Recently, outcomes for liver transplantation (LT) in highly selected ICC patients have significantly improved. This review compares the long-term prognosis of LT versus LR for ICC. METHODS: A systematic review of databases including Web of Science, MEDLINE, Scopus, and Cochrane CENTRAL for comparative studies on the long-term outcomes of LT versus LR for ICC was completed. The primary outcome was 5-year overall survival (OS). Meta-analysis was performed using random-effects models. RESULTS: A total of 7 retrospective comparative studies were included. A total of 5478 patients were analyzed (LT group: 346 patients; LR group: 5132 patients). Pooled analysis showed significantly improved long-term prognosis in the LT group compared to the LR group. Five-year OS was higher in the LT group (OR 0.59, 95% CI 0.37- 0.93, p&#x202f;=&#x202f;0.02) and 5-year recurrence-free survival (RFS) was also higher in the LT group (OR 0.44, 95% CI 0.22- 0.89, p&#x202f;=&#x202f;0.02), although the comparison of 1-year OS (p&#x202f;=&#x202f;0.52) and 3-year OS (p&#x202f;=&#x202f;0.88) between the LT and LR groups showed no significant difference. However, sensitivity analysis revealed that excluding one study resulted in changes to the statistical significance of both 5-year OS and 5-year RFS. This suggests that individual studies have some influence. CONCLUSIONS: LT may be associated with improved long-term survival and recurrence outcomes compared with LR for ICC; however, the evidence is limited and should be interpreted with caution. These findings suggest a potential benefit of LT in carefully selected patients, but further prospective studies are needed to confirm these results.

Humans

Predictors of transition readiness in adolescents with neurogenic lower urinary tract dysfunction.

PURPOSE: Adolescents with Neurogenic Lower Urinary Tract Dysfunction (NLUTD) face significant challenges in their quality of life and readiness to transition to adult healthcare services. This study examines the impact of various demographic and clinical factors on transition readiness. METHODS: We performed a retrospective review of prospectively collected data from 75 adolescents with NLUTD managed at a specialized tertiary referral pediatric facility. We employed multivariate linear regression analysis to explore the relationship between transition readiness scores collected from the Good2Go questionnaire, including the total transition readiness score and its sub-domains (self-advocacy, knowledge, self-care, and social support), and predictors such as age, sex, reconstructive surgery status, and clean intermittent catheter (CIC) usage. RESULTS: The mean age of participants was 16.74 years (SD 2.44). Reconstructive surgery had been performed in 32 % of patients, and 77.3 % were on CIC. Multivariate regression analysis indicated that age significantly predicted transition readiness across several domains. Each additional year of age was associated with a 4.40-point increase in the total transition readiness score, a 3.66-point increase in knowledge, a 4.26-point increase in self-advocacy and a 5.41-point increase in self-care. Conversely, CIC significantly negatively impacted the social support domain, with scores decreasing by 9.69 points. Reconstructive surgery was significantly associated with lower self-care scores, with an average decrease of 12.12 points among those who had undergone surgery. CONCLUSION: Age significantly improves transition readiness in adolescents with NLUTD, reflecting cognitive and developmental growth. However, the negative effects of CIC on social support and reconstructive surgery on self-care underscore the need for personalized interventions to optimize health outcomes during the transition to adult care.

Humans

Incidence of Cirrhosis in Fibrotic Metabolic Dysfunction-Associated Steatohepatitis: A Meta-Analysis of Placebo Arms from Randomized Clinical Trials.

BACKGROUNDS AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) with stage F2-F3 fibrosis represents the main target population for emerging pharmacotherapies. However, data on short-term progression to cirrhosis (F4) in this group remain limited. We aimed to evaluate the incidence of cirrhosis in placebo-treated patients with fibrotic MASH in randomized controlled trials (RCTs). METHODS: In this single-arm meta-analysis, we systematically searched PubMed and Cochrane Library from inception to December 13, 2024, for pharmacological Phase&#x2009;&#x2265;&#x2009;2 RCTs reporting cirrhosis events (detected in liver biopsy or clinical signs) among patients with fibrotic MASH receiving placebo. Incidence rates were pooled using generalized linear mixed models with Clopper-Pearson confidence intervals (CIs). RESULTS: We identified a total of 11 RCTs, including 586 patients with fibrotic MASH. Total follow-up was 657.23 person-years (PYs), with 83 cirrhosis events reported. The pooled incidence rate was 13.09 per 100 PYs (95% CI 7.81 to 21.12, I2&#x2009;=&#x2009;75.6%, &#x3c4;2&#x2009;=&#x2009;0.682). In subgroup analysis, the incidence of cirrhosis was 3.40 per 100 PYs in MASH F2 (95% CI 1.10 to 10.02, I2&#x2009;=&#x2009;0%, &#x3c4;2&#x2009;=&#x2009;0) and 17.90 per 100 PYs (95% CI 10.63 to 28.55, I2&#x2009;=&#x2009;70.2%, &#x3c4;2&#x2009;=&#x2009;0.561) in MASH F3, with significant differences between stages (p&#x2009;=&#x2009;0.006). Sensitivity analyses showed consistent estimates. Most RCTs were judged to have a low risk of bias. CONCLUSIONS: This study provides stage-specific data on cirrhosis incidence in fibrotic MASH, highlighting the high short-term risk associated with MASH F3 in trial settings. These data may inform benchmarks to guide event expectations, enrichment strategies, sample size assumptions, and the interpretation of future MASH clinical trials.

Humans

Transcranial Alternating Current Stimulation at 40 Hz Improves Social Functioning in Children With Autism Spectrum Disorder: A Randomized Clinical Trial.

BACKGROUND: Autism spectrum disorder (ASD) lacks rapid and effective interventions for its core social difficulties. The right temporoparietal junction (rTPJ), a critical hub for social cognition, together with gamma band abnormalities implicated in ASD, provides a promising neuromodulation target. METHODS: In this randomized, double-blind, sham-controlled trial, 47 children with ASD (39 male; mean [SD] age = 8.79 [2.71] years) were assigned to receive either 21 sessions of 40-Hz high-definition transcranial alternating current stimulation (tACS) targeting the rTPJ (3 sessions/day for 7 days) or sham stimulation, with assessments conducted at baseline, postintervention (week 1), and a 3-week follow-up (week 4). The primary outcome was change in Ohio State University Autism Rating Scale-DSM-5 (OARS-5) total scores. Secondary outcomes included the Aberrant Behavior Checklist-Second Edition, Social Responsiveness Scale-Second Edition, and Short Sensory Profile. Eye-tracking metrics during Frith-Happ&#xe9; animations were exploratory measures of theory of mind (ToM)-related social cognitive processing. RESULTS: The active group demonstrated significant improvements in OARS-5 total scores at week 1 (mean difference = -1.13, 95% CI [-1.78 to -0.47], p < .001) and week 4 (mean difference = -1.47, 95% CI [-2.20 to -0.74], p < .001). Improvements in selected behavioral and sensory domains were observed. Average fixation duration during ToM animations showed a significant group &#xd7; time interaction. No serious adverse events occurred. CONCLUSIONS: These findings suggest that 40-Hz tACS targeting the rTPJ may be associated with rapid improvements in ASD symptom severity, particularly social functioning, in children with ASD, while being well tolerated. Clinical significance requires further evaluation.

Humans

Analgesia for Awake Internal Jugular Vein Cannulation in Trauma Emergency Bay: A Randomized Comparison of Ultrasound-Guided Superficial Cervical Plexus Block With Local Infiltration.

BACKGROUND: Internal jugular vein (IJV) cannulation is a critical component of trauma resuscitation but is often associated with significant pain during vessel dilation and suturing when performed under local anesthetic (LA) infiltration. OBJECTIVES: We hypothesized that an ultrasound (USG)-guided superficial cervical plexus block (SCPB) would provide superior analgesia and improve procedural efficiency in awake trauma patients compared to standard LA infiltration. METHODS: This was a prospective, randomized study of conscious, adult trauma patients requiring IJV cannulation. Participants were randomized to receive either 10 mL of 1% lignocaine via ultrasound-guided SCPB (Group S) or LA infiltration (Group L). The primary outcome was procedural pain measured by Numeric Rating Scale (NRS 0-10) during skin puncture, vessel dilation, catheter insertion, and suturing. Secondary outcomes included total procedure time, Verbal Numeric Rating Discomfort Scale (0-10), and complications. RESULTS: We enrolled 60 patients, with 30 patients assigned to each study group. Median NRS pain scores were significantly lower in Group S compared to Group L at all procedural time points (p < 0.01). The total procedure time was reduced by approximately 50% in Group S (7.5 min [interquartile range (IQR) 6.0-9.3]) compared to Group L (15.5 min [IQR 9.5-16.5]; p < 0.01). Patient discomfort scores were also significantly lower in Group S (p < 0.01). No periprocedural complications were reported in either group. CONCLUSION: Ultrasound-guided SCPB may be a useful alternative to local infiltration for IJV cannulation in selected awake trauma patients, when performed by clinicians experienced in ultrasound-guided regional anesthesia. By providing comprehensive sensory coverage, the technique significantly reduces procedural time and enhances patient cooperation without need for systemic sedation.

Humans

Meta-analysis of prostacyclin therapy for persistent pulmonary hypertension with congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the efficacy and safety of prostacyclin in the treatment of persistent pulmonary hypertension in congenital diaphragmatic hernia. METHODS: A systematic literature search was conducted in four main databases (PubMed, Web of Science, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The protocol was registered in advance in the International Prospective of Systematic Reviews (CRD420261325458). RESULTS: A total of nine studies were included involving a total of 7009 infants in this systematic review and meta-analysis. GRADE assessment revealed substantial heterogeneity in the quality of evidence across outcomes, with most outcomes rated very low quality and only one rated moderate quality. Studies were performed meta-analysis, which showed the use of prostacylin resulted a statistically significant decrease in the OI compared to the control group (Mean Difference (MD), 9.34; I2 0%; p < 0.00001), no statistically significant in mortality (OR, 0.83; I2 84%; p = 0.70), ECMO (OR = 4.9; I2 98%; p = 0.27), BNP (std MD, 6.98; I2 98%; p = 0.31), FiO2 (SMD = 8.0;, I2 64%; p = 0.11), Systolic orientation of IVS curvature (SMD = 0.69; I2 97%; p = 0.32), Diastolic orientation of IVS differences (MD = 0.62; I2 93% p = 0.26). After applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. CONCLUSION: In conclusion, this meta-analysis has confirmed that prostacyclin may temporarily improve oxygenation. However, after applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. Further validation through high-quality studies are still needed. TRIAL REGISTRATION: PROSPERO: CRD420261325458.

Humans

One-carbon metabolism and chemotherapy-induced toxicities in patients with stage II-III colorectal cancer: a prospective cohort study.

BACKGROUND: One-carbon metabolism (OCM) is a target of the chemotherapeutic agent capecitabine. OBJECTIVES: We investigated OCM biomarker concentrations in relation to capecitabine-induced toxicities in patients with stage II-III colorectal cancer. METHODS: Within a prospective cohort, 297 patients receiving adjuvant capecitabine-based chemotherapy were included. Pretreatment plasma concentrations of the OCM biomarkers folate, vitamin B2, vitamin B6, vitamin B12, total homocysteine, methionine, serine, and glycine were determined. We also investigated whether associations differed according to methylenetetrahydrofolate reductase (MTHFR) C677T genotypes. Chemotherapy-induced toxicities were defined as toxicity-induced modifications of capecitabine treatment. To allow for inspection of shapes of the associations, restricted cubic splines and Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and sex. RESULTS: In total, 156 (53%) patients experienced toxicity-induced modifications of capecitabine treatment. Folate was not associated with toxicities in the overall population. Higher folate concentrations were associated with a lower risk of toxicities in patients with MTHFR C677T CT/TT genotype (HRperdoubling: 0.75; 95% CI: 0.57, 0.98) but not in patients with CC genotype (HRperdoubling: 1.17; 95% CI: 0.84, 1.63). Higher concentrations of vitamin B2 were associated with a lower risk of toxicities (HRperdoubling: 0.81; 95% CI: 0.67, 0.99), whereas higher glycine concentrations were associated with a higher risk of toxicities (HRperdoubling: 1.87; 95% CI: 1.18, 2.94). The association between vitamin B6 and vitamin B12 and toxicities appeared nonlinear. Homocysteine, methionine, and serine were not associated with toxicities. CONCLUSIONS: Future studies investigating whether nutrition-guided optimization of OCM biomarkers will result in improved treatment tolerance are warranted.

Humans