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PubMed2028

Parental son preference in childhood and sex differences in the risk of cardiovascular disease in middle-aged and older adults.

INTRODUCTION: Sex differences in cardiovascular disease (CVD) risk are examined through biological and clinical factors, with less attention to early-life social exposures. This study examined associations of childhood parental son preference with CVD risk, sex differences, and mediation by modifiable risk factors. METHODS: This cohort analysis included China Health and Retirement Longitudinal Study participants aged ≥45 years without baseline CVD. Parental son preference was assessed retrospectively in 2014; incident CVD was self-reported physician-diagnosed heart disease or stroke through 2020. Sampling-weighted, community-clustered Cox models estimated adjusted hazard ratios (aHRs) and 95% CIs. Sex was prespecified as an effect modifier; mediation by 13 risk factors used inverse-odds-ratio weighting. Data were collected from 2011 to 2020 and analyzed from 2025 to 2026. RESULTS: Among 8,079 participants (mean age, 57.5 years; 4,216 women [52.2%]), 1,820 (22.5%) reported parental son preference. Son preference was associated with higher CVD risk overall (aHR 1.23 [95% CI 1.04, 1.46]) and among women (aHR 1.25 [95% CI 1.03, 1.53]); among men, the estimate was 1.16 (95% CI 0.87, 1.56), with limited heterogeneity by sex (ratio of aHRs 1.06 [95% CI 0.72, 1.58]). Among women, risk was concentrated in the highest paternal (aHR 1.47 [95% CI 1.14, 1.90]) and maternal (aHR 1.50 [95% CI 1.12, 1.99]) preference categories. Modifiable risk factors mediated 5.8% (95% CI 1.9%, 9.7%) of the association among women, mainly through socioeconomic and psychosocial factors. CVD risk was highest with both son preference and high risk-factor burden overall (aHR 1.97 [95% CI 1.43, 2.73]) and among women (aHR 2.23 [95% CI 1.61, 3.10]). CONCLUSIONS: Parental son preference was associated with higher incident CVD risk, with the largest estimates in the highest paternal or maternal categories among women. Modifiable risk factors explained a modest proportion, supporting life-course cardiovascular prevention that considers sex-differentiated childhood environments alongside risk-factor modification.

cardiovascular disease↗

PubMed2026

Proteomic and phosphoproteomic profiles of time-dependent dynamic changes in LPS-induced macrophage polarization.

The temporal proteomic and phosphoproteomic reprogramming during early M1 macrophage polarization (0-6 h) remains poorly understood. We performed time-resolved proteomic and phosphoproteomic analyses of LPS-stimulated RAW264.7 macrophages at seven time points within 6 h. Time-clustering of differentially expressed molecules revealed two patterns: initial change with partial recovery, and sustained dysregulation. Upregulated proteins and phosphorylation sites were enriched in the Rho GTPase signaling pathway, T-cell receptor signaling pathway, NF-κB cascade, osteoclast differentiation pathway, and antiviral immune pathway. Downregulated pathways were associated with cell cycle regulation, chromatin remodeling, RNA metabolism, and mRNA processing, indicating resource reallocation to prioritize acute inflammatory responses. Kinase-substrate network analysis confirmed the mitogen-activated protein kinase (MAPK), cyclin-dependent kinase (CDK), protein kinase B (AKT), and ribosomal S6 kinase (RSK) families as core upstream phosphorylation regulators. Integrated analysis revealed synergistic and antagonistic relationships between proteomic and phosphoproteomic changes. This study provides a temporal molecular atlas of M1 polarization, delineating inflammatory signaling dynamics and offering a basis for therapeutic target discovery in inflammatory diseases. SIGNIFICANCE: Macrophage M1 polarization is a central event in innate immune defense against pathogenic invasion, yet its dysregulation is a pivotal driver of the onset and progression of a broad spectrum of inflammation-associated disorders, spanning autoimmune diseases, infectious conditions and inflammatory bone diseases, making the dissection of its molecular regulatory mechanisms an urgent research priority in immunology and translational medicine. Dynamic molecular events within 0-6 h after LPS stimulation are critical for initiating and shaping M1 inflammatory activation, yet systematic time-resolved proteomic and phosphoproteomic profiling remains insufficient.In this study, we comprehensively characterized temporal proteome and phosphoproteome changes at seven consecutive time points during macrophage polarization, clarified two distinct dynamic molecular patterns, identified core signaling pathways and key kinase regulators involved in inflammatory reprogramming, and uncovered the leading role of post-translational phosphorylation modifications in initiating polarization. This work delineates the time-series molecular atlas of early macrophage activation, provides novel insights into the temporal regulatory mechanism of inflammatory signaling networks, and lays a solid experimental foundation for exploring new intervention targets and regulatory nodes in clinical translational research.

Lipopolysaccharides↗

PubMed2026

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 19 433 patients (mean age, 62 years ± 14.2 [SD]; 21 814 men; 39 323 chest CT examinations, 19 190 pre-AI, and 20 133 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 20 000-22 000 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. © 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↗

PubMed2026

Therapeutic-drug-monitoring-based ATG Targeted Dosing Strategy in Unmanipulated Haploidentical Haematopoietic Stem Cell Transplantation: a randomized, multicenter, phase 3 clinical trial.

Anti-thymocyte globulin (ATG) has been a standard prophylaxis for graft-versus-host disease (GVHD). However, the pharmacokinetics of ATG in vivo vary significantly, and weight-based fixed dosing may not optimize efficacy while minimizing toxicity. We investigated the clinical results of a therapeutic-drug-monitoring (TDM)-based, dose-optimized ATG strategy versus weight-based fixed dosing in haploidentical haematopoietic stem cell transplantation (NCT05166967). Patients were randomly assigned in a 1:1 ratio to receive a targeted dose of ATG or a fixed dose of 10 mg/kg. The primary endpoint was the 365-day graft-versus-host disease-free and relapse-free survival (GRFS). From January 1, 2022, to January 16, 2024, 204 patients were enrolled, with 102 patients in each group. The 365-day GRFS was higher in the targeted dose group (66.7%) than in the fixed dose group (50.0%; hazard ratio [HR], 0.666; 95% confidence interval [CI], 0.4456 to 0.9954; P = 0.048). The cumulative incidence of moderate to severe chronic GVHD at day 365 was significantly lower in the targeted dose group (9.8%; 95% CI, 5.0 to 16.5) compared with the fixed dose group (22.5%; 95% CI, 15.0 to 31.1; P = 0.026). Fewer grade 3-5 infections were reported in the targeted dose group (44.1%) than in the fixed dose group (70.6%; P < 0.001). More patients in the targeted dose group achieved optimal ATG exposure (P = 0.007) and superior CD4+ T-cell reconstitution (P = 0.002). These findings support the clinical utility of a TDM-based individualized ATG dosing strategy that balances efficacy and toxicity for GVHD prophylaxis in allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05166967.

Humans↗

PubMed2026

Enhancing Hemoglobin Bart's hydrops fetalis syndrome prevention: a single-tube multiplex real-time PCR assay for the comprehensive detection of four significant α0-thalassemia deletions (--SEA, --THAI, --CR, and --SA) found in Thailand.

BACKGROUND: Hemoglobin (Hb) Bart's hydrops fetalis is a major public health concern in Southeast Asia, particularly in Thailand. Current screening strategies target the two most common α0 -thalassemia deletions (--SEA and --THAI). METHOD: In this study, we developed a single-tube multiplex real-time PCR assay for the simultaneous detection of four clinically relevant α0-thalassemia deletions (--SEA, --THAI, --CR, and --SA). The assay was validated using 538 clinical samples with diverse thalassemia genotypes and compared against conventional gap-PCR as the reference method. Analytical performance, including sensitivity, specificity, and limit of detection (LOD), was evaluated. In addition, clinical utility was assessed in 22 prenatal diagnosis cases at risk of Hb Bart's hydrops fetalis. RESULTS: The study cohort demonstrated substantial genetic heterogeneity, comprising 43 distinct genotypes. The developed assay achieved 100% sensitivity and specificity for all targeted deletions, with complete concordance with gap-PCR results. No cross-reactivity was observed with α+-thalassemia. The assay demonstrated a high analytical sensitivity with a LOD of 9.76 × 10-3 ng per reaction. Whereas in prenatal diagnosis, all 22 fetal genotypes were accurately identified, including five cases of homozygous --SEA and one rare compound heterozygous --SEA/--CR fetus. CONCLUSIONS: This study presents a rapid, accurate, and cost-effective multiplex real-time PCR assay capable of detecting both common and rare α0-thalassemia deletions in a single reaction. The assay demonstrates strong potential for implementation in routine clinical laboratories and large-scale population screening, contributing to improved prevention and control of severe thalassemia syndromes in high-prevalence regions.

Humans↗

PubMed2026

Origins and timing of somatic variants in the brain.

Somatic variants accumulate in human brain cells throughout the lifespan. Variant allele fraction has traditionally been used as a proxy for both the developmental timing of somatic variants and their functional effect, based on the assumption that earlier mutations are shared by larger cell populations and therefore have greater potential for severe phenotypes. However, recent discoveries challenge this simplified model. Variables such as developmental bottlenecks, lineage restriction, and cellular and molecular context play critical roles in shaping the distribution and functional impact of somatic variants in the brain. These insights support a shift toward a context-dependent framework for interpreting somatic mosaicism.

Humans↗

PubMed2026

Timing of OMERACT core domain measurement in gout clinical trials: a systematic review of randomised trials.

AIMS: The Outcome Measures in Rheumatology (OMERACT) initiative has endorsed core domain sets for gout trials. The aims of this study were to evaluate the time points and frequencies at which the gout core domains are measured in existing gout urate-lowering therapy and gout flare trials, and whether all collected measurements were reported. METHODS: Urate-lowering therapy (n = 29) and gout flare randomised clinical trials (n = 14) from 2005 were identified from a prior systematic review of core domain reporting. Data were extracted for the time points and frequencies at which each core domain was measured, as well as whether all collected measurements were reported. RESULTS: In urate-lowering therapy trials, the core domains were measured at seven different frequencies. Serum urate and gout flares were most commonly measured monthly, and tophus burden was most commonly measured three monthly. Reporting of all collected measurements varied, from 24/29 (83%) trials for serum urate to 0/2 (0%) trials for activity limitation. In gout flare trials, core domains were measured at nine different frequencies. Pain, joint tenderness and joint swelling were most commonly measured monthly. Reporting of all collected measurements varied, from 13/14 (93%) trials for pain to 3/8 (37.5%) trials for joint tenderness. CONCLUSION: In both urate-lowering therapy and gout flare trials, there is substantial variability in when the core domains are measured, and reporting of collected measurements is inconsistent. This work provides the foundation for a consensus process to establish standardised time points and frequencies for measuring the OMERACT-endorsed gout core domains.

Gout↗

PubMed2026

A New Highly Concentrated Insulin Aspart AT278 (500 U/mL) Demonstrates Ultra-Rapid Pharmacokinetic and Pharmacodynamic Properties in Type 2 Diabetes Regardless of BMI.

AIMS: To evaluate the pharmacokinetics, pharmacodynamics, and safety of a novel U500 insulin aspart formulation (AT278 [500 U/mL]; AT278-U500) compared with standard concentration insulin aspart (InsAsp [100 U/mL]; InsAsp-U100) and U500 human regular insulin (HumIns [500 IU/mL]; HumIns-U500). MATERIALS AND METHODS: This single-centre, randomised, double-blind crossover 12-h euglycaemic clamp study was conducted in 41 overweight and obese people with type 2 diabetes (BMI 25.0-38.7 kg/m2) receiving a single subcutaneous dose (0.5 U/kg) of AT278-U500 and InsAsp-U100. HumIns-U500 was consecutively studied open label in a 24-h clamp. RESULTS: AT278-U500 exhibited a significantly faster insulin absorption than InsAsp-U100 and HumIns-U500 (t Early50%Cmax: 9 min vs. 35 min vs. 55 min), leading to a significantly higher glucose-lowering effect within the first hour (AUCGIR,0-60min) compared with both InsAsp-U100 (treatment ratio 2.02 [95% CI 1.64; 2.50]) and HumIns-U500 (3.91 [2.89; 5.27]). When divided by median BMI (29.7 kg/m2), AUCGIR,0-60min was significantly higher with AT278-U500 in both the low-BMI and high-BMI subgroup compared to InsAsp-U100. Linear regression showed a significant inverse relationship between BMI and AUCGIR,0-60min for InsAsp-U100 (slope -0.142, p < 0.0001), whereas AT278-U500 showed no such relationship. Overall insulin exposure was similar for AT278-U500 and InsAsp-U100, while overall glucose-lowering effect was comparable across all three treatments. CONCLUSIONS: AT278-U500 maintains its ultra-rapid onset characteristics independent of BMI, representing the first ultra-rapid U500 option for prandial dosing in insulin-resistant people with type 2 diabetes requiring high-dose therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05754424.

Humans↗

PubMed2026

Visualizing the future: impact of holographic visualization on teaching minimally invasive veneer preparation: a randomized controlled trial.

BACKGROUND: Minimally invasive veneer preparation in prosthodontic education requires advanced spatial understanding and psychomotor precision. Although immersive technologies are increasingly used in dental education, evidence regarding the educational effectiveness of holographic visualization in prosthodontics remains limited. This randomized controlled trial evaluated the impact of holographic visualization on preparation quality and student-reported educational outcomes during preclinical training in minimally invasive veneer preparation. METHODS: Sixty undergraduate dental students were randomly assigned to receive either conventional two-dimensional photographic visualization (n = 30) or holographic three-dimensional visualization (n = 30). Following a standardized calibration session and baseline preparation, participants performed a second veneer preparation after exposure to the assigned visualization modality. Preparations were independently assessed by two blinded evaluators using a predefined scoring rubric. Within-group changes were analysed using Wilcoxon signed-rank tests, and between-group differences were assessed using analysis of covariance adjusted for baseline performance. Student-reported outcomes were compared using Mann-Whitney U tests with false discovery rate correction. RESULTS: Both groups showed significant improvements in preparation quality from baseline to post-intervention (both p < 0.001). However, no significant between-group differences were observed (adjusted mean difference: 0.60 points; 95% confidence interval: -0.48 to 1.67; p = 0.269). Overall student-reported outcomes were comparable between groups. Spatial understanding showed the largest between-group effect in favour of holographic visualization, although this difference was not significant after correction for multiple comparisons. Holographic visualization was highly accepted by students, and 70% supported its future integration into dental education. CONCLUSIONS: Although holographic visualization did not significantly improve immediate preparation quality compared with conventional two-dimensional photographs, it was highly accepted by students and showed the largest observed effect for perceived spatial understanding. These findings suggest that holographic visualization may primarily support spatial understanding and represent a valuable adjunct for teaching complex three-dimensional concepts in preclinical prosthodontic education. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00040713, prospectively registered on 22 June 2026.

Humans↗

PubMed2026

Assessing time to symptomatic progression, a patient-relevant efficacy endpoint, in the MARIPOSA study in non-small cell lung cancer.

INTRODUCTION: In the phase 3 randomized MARIPOSA study, amivantamab and lazertinib combination therapy demonstrated improved progression-free survival (PFS) and overall survival (OS) versus osimertinib in participants with previously untreated, epidermal growth factor receptor-mutated advanced non-small cell lung cancer. Time to symptomatic progression (TTSP) was introduced to assess clinical worsening and complement endpoints that investigate radiographic disease progression and patient-reported outcomes. TTSP provides an easily interpretable measure of disease-specific symptom worsening to further support patient experience. METHODS: In MARIPOSA, TTSP was quantitatively assessed as a secondary efficacy endpoint and defined as the time from randomization until participants experience disease-specific symptom worsening requiring a clinical intervention or treatment change, or death. To evaluate the impact of amivantamab and lazertinib on TTSP considering its established OS benefit against osimertinib, an exploratory analysis censoring death events was performed. RESULTS: At the final protocol-specified OS analysis (median follow up: 37.8 months), median TTSP was 43.6 months with amivantamab and lazertinib versus 29.3 months with osimertinib (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.57-0.83; p < 0.0001). Amivantamab and lazertinib reduced deaths following a TTSP event compared to osimertinib. A strong correlation between TTSP and PFS or OS was observed. CONCLUSIONS: Amivantamab and lazertinib significantly delayed TTSP versus osimertinib. TTSP offers a clinician-validated measurement of disease-specific symptom worsening, capturing symptoms perceived by patients that prompt clinical action. TTSP is highly correlated with PFS and OS, providing complementary insights alongside traditional endpoints. TTSP enhances understanding of treatment benefit and supports informed clinical decision-making by integrating patient experience.

Humans↗

PubMed2026

Association of Baloxavir Treatment Timing with Serial Interval and Household Transmission of Influenza through a Likelihood-Based Analysis.

BACKGROUND: Baloxavir treatment is associated with reduced influenza transmission within households, and the serial interval varies by treatment status. However, it remains unclear how baloxavir-induced changes in the serial interval relate to household transmission. We aimed to quantify the model-based association between baloxavir treatment timing and the serial interval and household transmission risk. METHODS: We conducted a household survey of influenza cases in Japan between October 2018 and February 2019. We defined the likelihood-based model integrating the serial interval distribution by treatment status and the secondary attack rate (SAR) using individual-level data from index cases. Using this model, we estimated the reduction in the serial interval associated with baloxavir treatment. RESULTS: Compared with untreated index cases, baloxavir-treated cases were estimated to have a serial interval density reduced by 21.42% following treatment. Treatment within 24 hours was associated with a 0.1685 reduction in the area under the curve, with smaller reductions as treatment was delayed. Earlier treatment was associated with a shorter, more concentrated distribution, whereas treatment 72 hours after onset resembled untreated cases. CONCLUSIONS: Our findings highlight that baloxavir treatment is associated with a shorter serial interval and lower estimated secondary household transmission risk. We provide model-based estimates suggesting that earlier administration is associated with a greater reduction in serial interval density and estimated transmission risk, which may inform public health strategies for infection control.

Influenza↗

PubMed2026

Examining early-phase symptom trajectories in interpersonal psychotherapy versus antidepressant medication for adults with depression: A dynamic time warp network analysis.

BACKGROUND: Depression is characterized by substantial symptom heterogeneity, which is often concealed when examining total severity scores. Analyzing symptom-level change can improve our understanding of treatment effects and recovery processes. This study, therefore, examined dynamic symptom networks during early-phase interpersonal psychotherapy (IPT) and selective serotonin reuptake inhibitor (SSRI) antidepressant treatment, assessing patterns of symptom change across as well as differences between treatments. METHODS: Using weekly item-level Hamilton Depression Rating Scale (HAM-D) data from a randomized clinical trial comparing IPT and SSRIs for adults with depression, this preregistered study examined symptom trajectories in the first six weeks of treatment with Dynamic Time Warping (DTW). RESULTS: Depressive symptom trajectories and DTW-based symptom networks were largely similar for IPT and SSRI. In both conditions, changes in somatic symptoms of anxiety and middle insomnia tended to precede improvements in depressed mood. CONCLUSIONS: Early symptom change may occur outside the core affective domain, underscoring the importance of monitoring symptoms broadly. Symptom-level patterns may reflect patients' stage of recovery and provide clinically relevant information beyond total severity scores. The absence of differences in improvement patterns between IPT and SSRI suggest few indications for treatment selection based on baseline symptom profiles. Future research should replicate and extend these findings to subsequent treatment phases using more frequent assessments and a broader range of interventions.

Humans↗

PubMed2026

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

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

Humans↗

PubMed2026

Comparison of Ketamine and Pregabalin on Postoperative Opioid Usage and Pain Management in Spinal Fusion: Systematic Review and Network Meta-analysis.

BACKGROUND CONTEXT: Spinal fusion is associated with substantial early postoperative pain and opioid exposure. Both ketamine and pregabalin are widely incorporated into Enhanced Recovery After Surgery (ERAS) protocols as opioid-sparing adjuncts. However, their comparative efficacy and safety in this specific setting remain uncertain. Our objective was to compare ketamine and pregabalin indirectly for early postoperative opioid consumption, pain, and adverse events in adults undergoing spinal fusion. METHODS: Pubmed, Embase, and Cochrane Trials were searched from inception through October 2025. Eligible studies were randomized trials enrolling adults undergoing instrumented spinal fusion, randomized to perioperative ketamine, pregabalin, or control, and reported extractable 24-hour opioid consumption or pain outcomes. Continuous outcomes were pooled as mean differences in MME or VAS units, and adverse events were reported descriptively. A connected treatment network was analyzed using random-effects models. Risk of bias (RoB) was assessed with the Cochrane RoB 2 tool. RESULTS: Thirteen trials (n=879) were included: ketamine (n=210), pregabalin (n=271), and control (n=398). Six trials contributed opioid data (3 ketamine, 3 pregabalin). Using pregabalin 150 mg as reference, ketamine was associated with lower 0-24-hour opioid use (MD -56.99 mg MME; 95% CI -99.56 to -14.43). Control (MD +21.31; 95% CI -1.05 to +43.66) and pregabalin 300 mg (MD -13.22; 95% CI -40.41 to +13.96) did not significantly differ from pregabalin 150 mg. Seven trials contributed 24-hour VAS data, with control being associated with higher pain versus pregabalin 150 mg (MD +0.84; 95% CI +0.01 to +1.66), while ketamine and pregabalin 300 mg were not k significantly different. Adverse events were generally infrequent and similar to control. CONCLUSIONS: Both ketamine and pregabalin provide early opioid sparing with comparable 24-hour analgesia. Ketamine showed a larger opioid-sparing point estimate, but indirect comparisons are imprecise. Adequately powered head-to-head trials with standardized protocols and adverse event reporting are needed.

Humans↗

PubMed2026

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

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

AP↗

PubMed2026

Bypassing the emergency department for testicular torsion.

BACKGROUND: Testicular torsion is a time-sensitive urologic emergency that can result in testicular ischemia, atrophy, and loss if detorsion is delayed. Patients transferred from outside hospitals oftentimes experience prolonged ischemia due to repetitive assessments in the receiving emergency department (ED) and lengthy interhospital transfers. To address these delays, our institution created a pathway allowing patients with a confirmed diagnosis of testicular torsion to bypass the ED and proceed directly to the OR. OBJECTIVE: To evaluate the efficacy of an emergency department bypass pathway on time to surgical intervention and testicular salvage rates for patients transferred from outside hospitals with confirmed testicular torsion. STUDY DESIGN: Following one year of pathway implementation and institutional review board approval, a retrospective chart review was performed. Patients aged 12-18 years that were transferred from outside hospitals for confirmed testicular torsion were included in the pathway. A pre-pathway cohort (January 2022-December 2022) of patients with ED management was compared to a post-pathway cohort (August 2023-September 2024) of patients managed via direct OR transfer. Comparisons included patient age, mean time from ED registration to surgery start, orchiectomy rates, testicular atrophy rates at follow-up, and overall length of follow-up. T-tests and Fisher's exact tests were used for statistical analysis. RESULTS: 71 patients were included. Mean time from registration to OR start was significantly shortened in the post-pathway cohort compared to the pre-pathway cohort (70 min vs. 23 min, p < 0.0001). This represents a 67% decrease in time to surgery. Post-pathway patients were significantly older than pre-pathway patients (15 years vs. 13 years, p = 0.0025). Orchiectomy rates did not significantly differ between the two groups (14% post-pathway and 28% pre-pathway, p = 0.2454). Similarly, no significant difference was observed for testicular atrophy at follow-up (17% post-pathway and 15% pre-pathway, p = 1.0). Mean length of follow-up was insignificant (90 days for post-pathway and 76 days for pre-pathway, p = 0.6605). DISCUSSION: Direct transfer to the OR with ED bypass significantly reduced time to surgical detorsion. Other variables such as orchiectomy and testicular atrophy rates were not significantly impacted. Patient-limited factors may have influenced outcomes, such as delays in symptom recognition and time to initial care. CONCLUSION: An ED bypass pathway for transferred patients with testicular torsion was highly effective at reducing time to surgical intervention. Although testicular salvage rates were not significantly affected, reducing ischemia time is clinically important and encourages pathway refinement and broader use.

Humans↗

PubMed2026

Timeliness of publication of randomized controlled trials in rheumatology: A systematic review.

OBJECTIVE: To systematically review the (1) timeliness of publication of randomized controlled trials (RCTs) in rheumatology, (2) impact of the COVID-19 pandemic on time to publication, and (3) factors associated with publication delays. METHODS: We searched Medline, Embase, EBM Reviews, Cochrane Central Register of Controlled Trials, and Scopus from January 1, 2018, to June 30, 2023 for Phase 3, superiority, parallel-design RCTs that evaluated any treatment for a rheumatologic illness or a rheumatologic treatment for COVID-19 and reported clinical primary efficacy outcome. Outcomes of interest were time to publication after trial completion and publication delay of >2 years after trial completion. RESULTS: 448 RCTs were included in this systematic review. Median time from completion to publication was 549 days and 65.9 % RCTs were published within 2 years of completion. Compared with RCTs on rheumatologic diseases, RCTs on COVID-19 were published sooner (253 vs. 549 days; p < 0.001) and were more likely to be published within 2 years (adjusted OR 9.49, 95 % CI 2.07 to 43.61). Compared with RCTs completed before March 1, 2020, RCTs completed after March 1, 2020, were published sooner (327 vs. 724 days; p < 0.001) and were more likely to be published within 2 years (adjusted OR 9.40, 95 % CI 5.14 to 17.21). Time from RCT completion to submission accounted for most (67 %) of the time to publication. CONCLUSIONS: Publication delay continues to be an important concern in dissemination of clinical research. Most of the delays in publication were attributable to delays in submission to journals after trial completion.

Humans↗

PubMed2026

Effects of intensive lifestyle interventions with calorie-carbohydrate-restricted diet versus time-restricted eating on appetite and binge eating in type 2 diabetes: A randomized controlled trial.

The impact of intensive lifestyle interventions on appetite regulation and binge eating in individuals with type 2 diabetes (T2D) remains unclear. This study evaluated the effects of combined lifestyle interventions on appetite responses and binge eating in overweight or obese adults with T2D. In a randomized trial, 120 participants with T2D were allocated to three groups (n = 40 each): (1) Calorie-carbohydrate restriction (CCR), (2) Time-restricted eating with CCR (TRE + CCR), or (3) Control. Intervention groups received structured exercise and behavioral education based on the Information-Motivation-Behavioral Skills model. Appetite perceptions (hunger, satiety, desire to eat, and prospective food consumption) and binge eating (Binge Eating Scale; BES and objective binge episodes) were evaluated at baseline, week 12, and week 24 using linear mixed models. Both CCR and TRE + CCR significantly improved subjective appetite compared with the control group at 12 and 24 weeks (all p < 0.01). At 24 weeks, hunger decreased by -24.1 mm (95% CI: -35.8, -12.5) in the CCR group and -32.7 mm (95% CI: -44.2, -21.3) in the TRE + CCR group. Satiety also increased by 21.7 mm (95% CI: 9.46, 33.9) and 29.4 mm (95% CI: 17.4, 41.4), respectively. Significant reductions were observed for desire to eat and prospective food consumption. In contrast, changes in BES and objective binge episodes were not significantly different between groups at any time point. No significant differences were detected between the CCR and the TRE + CCR groups. Intensive lifestyle interventions incorporating CCR or TRE + CCR effectively reduced appetite in adults with T2D but did not significantly affect binge eating. Future research should target individuals with higher baseline BES scores to clarify potential benefits for binge eating behavior.

Humans↗