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PubMed2026

Artificial intelligence-supported double reading in European population breast cancer screening: A systematic review and meta-analysis of prospective programs.

BACKGROUND: Most European population mammography screening programs rely on double reading with arbitration, a model that delivers mortality benefit but is increasingly challenged by radiologist workload, variable specificity, and interval cancers. Artificial intelligence (AI) is being evaluated to support or optimize these established European screening pathways. PURPOSE: To synthesize prospective or program-embedded evaluations of AI conducted within European-style population screening programs and to estimate exploratory program-level absolute risk differences (RDs) per 1000 examinations for cancer detection rate (CDR) and recall. MATERIALS AND METHODS: We performed a prespecified, focused evidence synthesis of three large studies embedded within routine population screening programs operating under European-relevant workflows: MASAI (randomized AI-supported risk triage within a national program), ScreenTrustCAD (prospective paired-reader evaluation with AI as an independent reader in a double-reading framework), and PRAIM (nationwide decision-referral implementation). Outcomes were harmonized as AI-control RDs per 1000 examinations. Random-effects pooling used Hartung-Knapp-Sidik-Jonkman models. For the paired-reader design, sensitivity analyses applied a Kish effective sample-size approach across plausible within-examination correlations (ρ = 0.3-0.8). Positive predictive value (PPV) and workflow/time outcomes were summarized descriptively. RESULTS: Across 597,419 examinations, the pooled CDR RD was +0.9 per 1000 (95% CI -0.0 to +1.8; I2 ≈ 12%), consistent with a modest directional increase with borderline statistical uncertainty. The pooled recall RD was -0.6 per 1000 (95% CI -3.1 to +2.1; I2 ≈ 41-43%), indicating no consistent recall increase across screening programs. Where reported, PPV was higher with AI-supported screening. Efficiency signals included 44.3% fewer total readings in MASAI and shorter reading times for AI-normal examinations in PRAIM; in PRAIM, a program-level safety-net mechanism recovered 204 cancers that would otherwise have been missed. CONCLUSION: In European population screening programs characterized by double reading and arbitration, prospective program-embedded evidence suggests that AI integration may yield a small absolute increase in cancer detection (≈1/1000) without a consistent increase in recall, alongside improved PPV and efficiency signals. These findings suggestAI primarily as a complementary reader within European screening workflows, with implementation requiring explicit quality assurance and monitoring of interval cancers and stage distribution.

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PubMed2026

Stage-specific ROMO1 in rheumatoid arthritis: predictive immune insights into the MIF pathway and HLA-DR/IL2RA axis via integrated GWAS, transcriptomic, single-cell, and spatial profiling.

Emerging evidence links reactive oxygen species modulator 1 (ROMO1), a key mitochondrial ROS regulator, to rheumatoid arthritis (RA) pathogenesis. However, its exact mechanism remains elusive given the conflicting evidence about its specific function. We used a four-level integrative framework combining multi-omics data and literature‑supported mechanistic inference. At the genetic level, Mendelian randomization (MR) was performed to explore potential causal relationships between ROMO1, IL2RA, HLA-DR, MIF, and RA risk, followed by differential expression analysis and machine learning-based feature selection to identify key mROS genes. The temporal expression dynamics of ROMO1 were assessed in RA progression. At the cellular and tissue levels, we integrated single-cell RNA sequencing and spatial transcriptomics to map cell-type-specific expression and synovial localization of ROMO1-related immune cells and pathways. Finally, our multi-omics findings were contextualized with literature-supported mechanistic inference. (1) MR results were consistent with a potential protective effect of ROMO1 on RA (OR = 0.52) and its potential regulation of risk factors IL2RA (OR = 0.46) and HLA-DR (OR = 0.40). Conversely, IL2RA (OR = 1.42), HLA-DR (OR = 1.88), and MIF (OR = 1.17) were positively associated with RA risk. Additionally, ROMO1 was identified as a top candidate diagnostic predictor with stage-specific dynamics: downregulated in the early but upregulated in the late/remission stages. (2) Single-cell RNA sequencing showed ROMO1's cell-specific expression in CD14+ HLA-DR+ CD74+ monocytes and CD4+ IL2RA+ T cells. Cell communication analysis further suggested that these cells may participate in MIF pathway regulation. Spatial transcriptomics subsequently identified that ROMO1-related cells localized to synovial pathological regions, with MIF pathway changes correlated with RA progression. (3) Finally, literature-supported mechanistic inference suggests that ROMO1 may modulate mROS levels to promote anti-inflammatory M2 macrophage polarization, which could theoretically contribute to reduced systemic inflammation and the alleviation of multi-organ decline in RA. This integrated multi-omics investigation, supported by literature-based mechanistic inference, suggests ROMO1 as a stage-dependent biomarker candidate and potential immune regulator in RA.

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PubMed2026

Artificial intelligence enabled social robotic interventions (PARO) in Australian dementia care: A systematic review and meta-analysis.

BACKGROUND: Although there is a growing body of research indicating that Personal Robot/Social Robot could be used in various aspects of care for individuals with dementia, little is known about how well these types of interventions work in an actual hospital setting in Australia. AIMS & OBJECTIVES: The objective of the present systematic review and meta-analysis is to assess the effectiveness of PARO-based socially assistive robotic intervention in terms of its effectiveness outcomes towards the reduction of dementia-related behavioural and psychological symptoms in Australian based healthcare settings. METHODS: A systematic search was conducted across five electronic databases, including MEDLINE (PubMed), EMBASE, CINAHL, PsycINFO, and the Cochrane Library, to identify randomised controlled trials (RCTs) investigating PARO-based socially assistive robotic interventions for dementia in Australian healthcare settings. This review was registered with PROSPERO (CRD420251251916) and followed the PRISMA 2020 guidelines. In addition, the Cochrane Risk of Bias tool (RoB 2) was used to evaluate the risk of bias across all studies. Pooled standardised mean differences (SMD) with 95 % confidence intervals (CI) were calculated for agitation, anxiety, and depression. Heterogeneity across studies was evaluated using the I2 statistic. RESULTS: Six RCTs involving 1444 participants were identified for inclusion in this review. AI-enabled socially assistive robotic interventions, specifically the PARO therapeutic robot, significantly reduced agitation and anxiety when compared to standard treatment or control conditions. The pooled analysis showed that agitation [SMD = -0.44 (95 % CI: -0.70, -0.18) p = 0.0008] and anxiety [SMD = -0.59 (95 % CI: -0.91, -0.27) p = 0.0003] were reduced significantly, while the decrease in depression [SMD = -0.44 (95 % CI: -0.95, -0.07) p = 0.09] scores was non-significant among dementia patients receiving PARO-based socially assistive robotic interventions as compared to the control. The overall risk of bias across all six studies was considered low to moderate. CONCLUSION: PARO-based socially assistive robotic interventions may provide preliminary evidence of effectiveness in reducing agitation and anxiety in individuals with dementia in Australian healthcare, but the evidence regarding the reduction of depression remains unclear. Therefore, additional high-quality trials with consistent methodology and extended follow-up will be necessary to determine both the short-term and long-term clinical efficacy and practicality of implementing these interventions into practice.

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PubMed2026

A comparative systematic review of pharmacist education systems and pharmacy service quality in ASEAN-5: Indonesia, Malaysia, Thailand, the Philippines, and Singapore.

BACKGROUND: The global transition toward patient-centered pharmaceutical care has exposed structural disparities in ASEAN pharmacy workforce training and deployment. This review examines four research questions: how pharmacy education systems and accreditation standards differ across Indonesia, Malaysia, Thailand, the Philippines, and Singapore (collectively, the ASEAN-5); the extent to which pre-registration education influences clinical service scope and professional confidence; how education reform and regulatory change have shaped pharmacist clinical roles; and what barriers and enablers exist for regional qualification harmonization. METHODS: A systematic literature review following PRISMA 2020 was conducted. Searches of PubMed/MEDLINE and Scopus, supplemented by grey literature, were completed in May 2026. Of 78 unique records screened, 46 studies published between 2005 and 2026 met inclusion criteria. Quality appraisal used an adapted Mixed Methods Appraisal Tool; synthesis employed narrative thematic analysis. RESULTS: The five countries represent four structurally distinct pharmacy education architectures: Thailand's standardized six-year Doctor of Pharmacy with dual specialization tracks; four-year Bachelor of Pharmacy programmes in Malaysia and the Philippines with institutional variation; Indonesia's clinically underdeveloped system despite rapid expansion; and Singapore's four-year Bachelor of Pharmacy followed by a nationally mandated one-year pre-registration pathway. Evidence links deeper clinical training to broader practice scope, higher confidence, and improved patient outcomes. Reform produced uneven results: Thailand's PharmD transition improved clinical recognition but exposed deployment paradoxes; Singapore achieved the strongest training-to-practice alignment; Indonesia's health insurance reforms were not absorbed by an underprepared workforce; the Philippines lacks a national competency framework. No binding mutual recognition arrangement was identified; divergent qualification structures, incompatible accreditation systems, and an asymmetric evidence base remain the primary barriers. DISCUSSION: These findings indicate that clinical service scope is bounded less by national policy ambition than by the depth and clinical orientation of the pre-registration education that precedes it, and that credentialing reforms which outpace a health system's capacity to absorb new clinical roles, or the reverse, do not by themselves translate into expanded practice. CONCLUSIONS: Pharmacy education across the ASEAN-5 remains nationally distinct and clinically uneven. Clinical service scope is directly bounded by pre-registration education quality. No country has fully closed the education-practice gap. Regional harmonization requires national-level educational reform as a prerequisite.

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PubMed2026

Safety Profile of the Non-steroidal Anti-inflammatory Drug Celecoxib in the Short-Term Management of Acute Non-cancer Pain: A Systematic Review with Meta-analysis of Randomised Controlled Trials.

OBJECTIVE: To summarise the literature regarding the safety of short-term use of the non-steroidal anti-inflammatory drug (NSAID) celecoxib. STUDY DESIGN: Systematic review with meta-analysis of randomised trials. Participants comprised individuals of all ages with acute non-cancer pain. Interventions included celecoxib at 200-400 mg/day for up to 10 days. The comparators were placebo, other NSAIDs (including cyclooxygenase-2 [COX-2] inhibitors and non-selective NSAIDS [nsNSAIDS]), or opioids. DATA SOURCES: Five databases were searched from inception to April 2025: Embase, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus. Additionally, a registry was searched: ClinicalTrials.gov. DATA SYNTHESIS: Meta-analyses using Mantel-Haenszel and random-effects model were used to calculate risk ratios (RRs) and 95% confidence intervals (CIs) for severe cardiovascular, respiratory, and gastrointestinal adverse events and secondary outcomes. The Cochrane Risk of Bias Tool for randomised trials (RoB-2) was used to assess bias risk. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) was conducted to assess the certainty of evidence of each reported outcome. RESULTS: Title/abstract and full text screening comprised 3976 and 273 studies, respectively. Fifty studies were included with 10,693 participants. The RRs for adverse events were no different between celecoxib and placebo for severe events (3 studies) (RR 0.44 [95% CI 0.10-2.03]), cardiovascular (3 studies) (RR 0.84 [95% CI 0.24-2.92]), respiratory (4 studies) (RR 1.23 [95% CI 0.29-5.26]), and gastrointestinal events (33 studies) (RR 0.96 [95% CI 0.64-1.43]). There was no difference between celecoxib and NSAIDS for gastrointestinal adverse events, RR 0.89 (95% CI 0.68-1.17). Celecoxib had a lower risk compared to opioids for gastrointestinal events, RR 0.34 (95% CI 0.14-0.86), and showed a lower risk of nausea compared with placebo, RR 0.75 (95% CI 0.60-0.93), and nsNSAIDS, RR 0.80 (95% CI 0.64-0.99). Most studies had some risk of bias concerns, and the overall certainty of evidence for most outcomes was very low. Celecoxib appears to be safe for acute non-cancer pain when compared to placebo, NSAIDS, and opioids. It had a lower risk compared to opioids for gastrointestinal adverse events in general, nausea and vomiting, as well as a lower risk for nausea adverse events when compared to placebo and nsNSAIDS. REGISTRATION: PROSPERO-CRD42025642152.

Journal Article↗

PubMed2026

Efficacy and safety of Janus kinase inhibitors in Behçet's disease: A systematic literature review.

INTRODUCTION: Behçet's disease e (BD) is a chronic, relapsing, multisystem inflammatory disorder that if not successfully treated can lead to severe, organ or life-threatening complications. Despite treatment with glucocorticoids, immunosuppressants, and tumor necrosis factor (TNF) inhibitors, some patients still have refractory disease that mandates additional therapeutic options. The pathogenesis of BD involves dysregulated innate and adaptive immune responses with multiple cytokines signaling through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. By targeting multiple inflammatory pathways, JAK inhibitors have emerged as a promising therapeutic option. However, current evidence remains limited and heterogeneous. Therefore, we conducted this systematic review to evaluate their efficacy and safety in BD. METHODS: We conducted a systematic literature review in accordance with PRISMA 2020 guidelines (PROSPERO registration: CRD420261381955). PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched from inception to March 2026. Original clinical studies evaluating Janus kinase (JAK) inhibitors in BD were included. Two reviewers independently performed study selection, data extraction, and quality assessment using Joanna Briggs Institute tools. Due to heterogeneity, results were synthesized narratively, focusing on efficacy and safety outcomes. RESULTS: Seventeen studies (99 patients) were included, predominantly case reports and small observational cohorts with overall high methodological quality. All evaluated tofacitinib, baricitinib, or upadacitinib, with no data on other JAK inhibitors. Patients were highly treatment-refractory, with prior failure of conventional and biologic therapies. Upadacitinib was the most frequently studied agent and demonstrated an overall response rate of 85.2% and complete remission in 59.3% in a multi-center study. Efficacy was observed across multiple domains, with the most consistent responses in intestinal disease, including clinical and endoscopic remission, alongside frequent glucocorticoid-sparing effects. Safety findings were consistent with known JAK inhibitor safety profiles, with mainly mild to moderate infections and manageable laboratory abnormalities, and no clear signal for increased thrombotic events, although follow-up was limited. CONCLUSION: JAK inhibitors demonstrate promising efficacy in BD, particularly in refractory and multisystem disease. The most consistent evidence of efficacy was observed in gastrointestinal involvement, whereas data for other disease domains remain limited. Their safety profile appears consistent with existing data, although further follow up and validation is required. High-quality randomized controlled studies are an imminent need to study the potential role of JAK inhibitors in BD.

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PubMed2026

Changes in heroin-related ambulance attendances following the introduction of a medically supervised injecting room in Victoria, Australia.

BACKGROUND: Injecting drug use contributes significantly to morbidity, mortality and broader social harms globally. Supervised Injecting Facilities (SIFs) are harm reduction interventions that reduce overdose risk and facilitate access to health services for marginalised individuals. While international evidence supports the effectiveness of SIFs, Australian population-level surveillance data quantifying their impact on emergency medical service utilisation remain limited. METHODS: Using data from the National Ambulance Surveillance System, we conducted a retrospective, interrupted time series analysis of heroin-related ambulance attendances within the local catchment of the Medically Supervised Injecting Room (MSIR) between January 2015 and December 2023. Supplementary analysis included comparisons with central Melbourne suburbs and the broader state of Victoria. Key intervention timepoints, including the opening of the MSIR on 30 June 2018, expansion of its operating hours in July 2019, and the COVID-19 pandemic from April 2020 to October 2021, were examined to assess changes in heroin-related attendances over time. Segmented regression models were used to assess changes in heroin-related ambulance attendance trends over time. RESULTS: At the time the MSIR opened, the model-predicted heroin-related ambulance attendance rate within the MSIR catchment was 123 per 100,000 population per month, equivalent to approximately 48 heroin-related ambulance attendances per month. Prior to implementation, the attendance rate was increasing by an estimated 0.74 per 100,000 population per month. Following the opening of the MSIR, the previously increasing trajectory reversed, with ambulance attendance rates declining by approximately 2.3 per 100,000 population per month relative to the pre-intervention trend. By the end of the study period (December 2023), the predicted monthly heroin-related ambulance attendance rate had declined to 36 per 100,000 population (approximately 14 attendances per month), representing an overall reduction of 70.7% from the time of MSIR implementation. These reductions persisted throughout the COVID-19 lockdown period and were sustained after restrictions lifted. Supplementary analysis showed no comparable reductions in the central Melbourne region or the remainder of Victoria. CONCLUSIONS: The introduction of the MSIR in Richmond was associated with a sustained reduction in heroin-related ambulance attendances within its catchment area. These findings provide strong population-level evidence that SIFs reduce acute heroin-related harms requiring emergency ambulance response, reinforcing their role as an effective harm reduction strategy within the Australian context.

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PubMed2026

Unanticipated Effects of Parental Social Media Use: Guidance for Clinicians.

"Sharenting," the practice of parents posting photographs, videos, and information about their children on social media, has an ever-growing presence in modern society. However, researchers and the public are now recognizing the potential consequences of sharing, including creation of permanent digital footprints, strained familial relationships, and threats to children's safety. Despite this emerging evidence, no U.S. clinical or legal guidelines exist for parents on safe sharing. Visits with behavioral health providers and family physicians can serve as key points for intervention. This column aims to provide clinicians with a better understanding of sharenting and its potential effects on patients and families, guidance on discussing safe online sharing, and a tool for parents and other caregivers to use when deciding whether to post.

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PubMed2026

Ribosomal protein S3: a critical regulator of human disease mechanisms.

Ribosomal protein S3 (RPS3) is an essential structural component of the 40S ribosomal subunit, yet growing evidence highlights crucial extraribosomal roles in genome maintenance, cell-cycle control, and immune signaling. Dysregulation of RPS3 contributes to diverse human disorders, including cancer, inflammatory diseases, neurodegeneration, and resistance to antimicrobial and anticancer therapies. As a cofactor of NF-κB and a participant in DNA damage responses, RPS3 occupies a node that integrates stress signaling with transcriptional reprogramming, enabling both protective and pathological outcomes. The present review critically evaluates mechanistic insights into RPS3 biology, emphasizing recent findings that delineate its context-dependent effects, discrepancies across models, and remaining gaps that restrict translational applications. Understanding these complexities is essential to assess RPS3's potential as a biomarker and therapeutic target.

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PubMed2026

Fracture-related infection following open forefoot fractures caused by dropped objects.

INTRODUCTION: This study evaluated the rate of fracture-related infection (FRI) of open forefoot fractures caused by dropped objects, and examined associations of treatment characteristics, including intravenous and oral antibiotics and operative debridement, with FRI. METHODS: Patients aged 18-80 years who sustained an open metatarsal or phalanx fracture caused by a dropped object between January 2021 and June 2024 were retrospectively identified from two Level 1 trauma centers. The primary outcome was FRI, determined based on the FRI consensus criteria. FRI rates were compared between those who underwent irrigation and debridement (I&D) at bedside versus in the operating room, and between those who received oral versus intravenous (IV) antibiotics. Patient characteristics were also analyzed to determine host factors associated with FRI. RESULTS: A total of 86 patients (median age 41 years [IQR: 29-56], 58% male) were included. Eighty-five patients (99%) received antibiotics, 31 (36%) of whom received intravenous antibiotics. Sixty-six patients (77%) received an I&D at presentation, 57 (66%) at bedside and 9 (10%) in the operating room. Thirteen patients (15%, 95% CI: 8.3%-24%) developed FRI. No significant difference in FRI rate was found between patients who underwent I&D at bedside versus in the operating room (12% versus 11%, p > 0.99). Among patients who did not undergo I&D in the operating room, no significant difference in FRI rate was found between patients who received oral versus IV antibiotics (17% versus 13%, p = 0.74). Insulin-dependent diabetes was associated with an increased risk of FRI (60% versus 12%, p = 0.02). CONCLUSIONS: In this cohort, one in seven patients developed FRI. No statistically significant differences in FRI rates were observed by I&D setting (bedside versus operative) or antibiotic route (oral versus IV), including in a subgroup analysis excluding patients treated with operating room I&D. These findings are limited by sample size and potential treatment selection bias and should not be interpreted as evidence of equivalence. Management should be individualized based on clinical judgement, resource availability, and patient factors. These findings can help guide the management protocols for "dropped objects" open forefoot fractures presenting to urgent care and the emergency department. LEVEL OF EVIDENCE: Therapeutic Level III.

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PubMed2026

Primary ACL Repair and Reconstruction in Isolated ACL Ruptures: Forgotten Joint Scores and the Association Between Residual Laxity and Joint Awareness.

BACKGROUND: Primary anterior cruciate ligament (ACL) repair has recently reemerged as a treatment option for carefully selected proximal ACL tears. However, evidence regarding patient-reported joint awareness and the relationship between postoperative laxity and joint awareness remains limited. PURPOSE: To compare joint awareness, clinical outcomes, and postoperative laxity between primary ACL repair and hamstring tendon autograft reconstruction in carefully selected patients with isolated ACL rupture, and to explore the association between residual laxity and postoperative joint awareness. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective cohort study included 85 patients with isolated ACL rupture treated with either primary ACL repair (n = 26) or hamstring autograft reconstruction (n = 59), with a minimum follow-up of 24 months. Clinical outcomes, including visual analog scale score, Lysholm score, International Knee Documentation Committee (IKDC) score, Tegner activity scale score, postoperative knee laxity, return to sport, and rerupture rates, were evaluated. The authors also used the Forgotten Joint Score-12 (FJS-12), a measure of joint awareness, to evaluate patients. A higher score reflects lower joint awareness, suggesting function more similar to a native knee. Multivariable regression analyses were performed to evaluate variables associated with postoperative FJS-12 values. RESULTS: No differences were observed between groups in postoperative Lysholm, IKDC, and Tegner activity scale scores; Lachman- and pivot-shift-assessed postoperative laxity; and return-to-sport rates. However, postoperative FJS-12 values were significantly higher in the repair group compared with the reconstruction group (87.0 ± 15.0 vs 77.5 ± 14.2; mean difference, 9.5 points [95% CI, 2.8-16.3]; P = .006), corresponding to a moderate effect size (Cohen d = 0.66). Secondary exploratory regression analyses demonstrated that residual postoperative laxity was associated with lower postoperative FJS-12 values in both Lachman- and pivot-shift-based models (R2 = 0.649 and 0.680, respectively; P < .001 for both). CONCLUSION: In carefully selected patients with proximal ACL tears and adequate tissue quality, no significant between-group differences were detected in conventional clinical outcomes, postoperative laxity, return-to-sport rates, or rerupture rates between primary ACL repair and reconstruction. Primary ACL repair was associated with higher postoperative FJS-12 values at short- to midterm follow-up, suggesting function more similar to that of a native knee. Residual postoperative laxity was associated with lower FJS-12 values in secondary exploratory analyses.

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PubMed2026

Efficacy and Safety of Psychedelic Microdosing on Psychological Outcomes in Healthy Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Psychedelic microdosing has gained increasing popularity for enhancing mood and cognition, yet its effects on psychological outcomes in healthy adults remain unclear. We aim to evaluate the efficacy and safety of psychedelic microdosing on psychological outcomes in healthy/non-clinical adult population. METHODS: This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251035294). We searched Embase, MEDLINE, and PsycINFO from inception to February 2026 for original studies in healthy adults using sub-hallucinogenic psychedelic doses on separate days. We included randomized studies, nonrandomized prospective studies, cross-sectional studies, and observational longitudinal designs and stratified meta-analyses by design. Random-effects models were used; safety in randomized controlled trials (RCTs) was pooled as risk differences (RDs). Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design. RESULTS: 24 studies (3,681 participants) met inclusion criteria, 6 contributed to meta-analyses. RCTs of psilocybin and LSD microdosing showed subjective and neurophysiological effects but minimal impact on cognition, creativity, or sustained mood. Psilocybin altered EEG and speech with little behavioral change, while LSD caused transient mood and minor physiological effects without lasting cognitive or personality benefits. Observational studies indicated mood and personality improvements, likely influenced by expectancy or lifestyle factors. Meta-analyses included two parallel RCTs (3 comparisons; n = 117) and three non-RCT studies (n = 1,013). Adverse event analyses included two RCTs (4 comparisons; n = 109). RCTs showed no clear evidence of immediate symptom reduction: depressive symptoms (SMD = -0.19; 95% CI -0.56, 0.19; I2 = 0%), anxiety (SMD = -0.20; 95% CI -1.11, 0.71; I2 = 82.3%),and stress (SMD = 0.02; 95% CI -0.39, 0.43; I2 = 0%). Non-RCT within-arm estimates were imprecise and heterogeneous for depressive symptoms (SMCC -0.33; 95% CI -0.75, 0.08) and anxiety (SMCC -0.29; 95% CI-0.84, 0.26). Exploratory pooling across all designs suggested decreases in depressive symptoms and stress, while anxiety remained uncertain. Adverse event risks were similar between treatment and control. CONCLUSIONS: Microdosing does not show consistent immediate benefits for depressive, anxiety, or stress symptoms in healthy adults, and evidence from RCTs remains inconclusive. Although improvements were observed in some studies, these effects were not significantly different from placebo. Larger, well-designed RCTs are needed to clarify the efficacy and safety of psychedelic microdosing beyond placebo.

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PubMed2026

Comparative efficacy and safety of pharmacokinetically guided and body surface area-based 5-fluorouracil dosing in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Body surface area (BSA)-based 5-fluorouracil (5-FU) dosing remains the standard in colorectal cancer despite substantial interpatient pharmacokinetic variability, which may lead to underexposure, treatment failure, or severe toxicity. This systematic review and meta-analysis evaluated whether pharmacokinetically guided 5-FU dosing improves efficacy and safety compared with conventional BSA-based dosing. METHODS: PubMed/MEDLINE, Embase, and Scopus databases were searched from inception to the final search date. The search identified 1,802 records: PubMed/MEDLINE, 47; Embase, 118; and Scopus, 1,637 records. Comparative randomized and non-randomized studies evaluating pharmacokinetically guided, area under the curve-guided, or therapeutic drug monitoring-based 5-FU dosing versus BSA-based dosing in colorectal cancer were included. Random-effects models were employed. The risk of bias was assessed using RoB 2 and ROBINS-I, and the certainty of evidence was evaluated using GRADE. RESULTS: Five studies comprising 809 unique patients were included. Across the primary severe-toxicity analysis, the pooled denominator was 1,338 reported observations, including 625 in the PK-guided 5-FU dosing arm and 713 in the BSA-based 5-FU dosing arm, because one study reported severe toxicity by treatment cycle rather than by patient. PK-guided dosing was associated with lower severe or grade ≥ 3 toxicity (RR 0.50, 95% CI 0.33-0.76; P = 0.001; I²=79%). PK-guided dosing was also associated with a higher objective response rate (RR 1.50, 95% CI 1.24-1.80; P < 0.0001) and disease control rate (RR 1.18, 95% CI 1.07-1.30; P = 0.001). Severe diarrhea was reduced (RR 0.33, 95% CI 0.18-0.62; P = 0.0006), whereas mucositis, neutropenia/leukopenia, and hand-foot syndrome were not significantly different between dosing strategies. CONCLUSION: PK-guided 5-FU dosing was associated with lower severe toxicity and diarrhea and higher objective response and disease-control rates than conventional BSA-based dosing. However, the evidence was derived from a small and clinically heterogeneous group of studies, and progression-free or overall-survival benefits could not be established. The findings apply predominantly to metastatic colorectal cancer treated with infusional 5-FU within FOLFOX- or FOLFIRI-based regimens. CLINICAL TRIAL REGISTRATION: Not applicable. This study was a systematic review and metaanalysis, and not a clinical trial.

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PubMed2026

Evaluating the utility of melatonin in spine surgery: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Spine surgery is increasingly performed worldwide, and acute postoperative stressors such as pain and anxiety remain highly prevalent despite historical management with opioids and other pharmacological agents. Recently, interest has emerged in melatonin administration given its endogenous physiological roles, low cost, favorable adverse event profile, and documented benefits throughout surgical literature. PURPOSE: This study aims to consolidate the existing evidence on melatonin's utility specifically in spine surgery, an area not yet comprehensively evaluated, to inform clinical practice and enhance spine surgeon comprehension. STUDY DESIGN/SETTING: Preregistered on PROSPERO, this systematic review queried PubMed/MEDLINE, CINAHL, SPORTDiscus, and Web of Science on November 21st, 2025, for studies reporting outcomes following melatonin administration in patients undergoing spine surgery. METHODS: Study quality was assessed using the Cochrane Risk-of-Bias 2 tool. Extracted variables included demographics, comparator medications, dosages, and other relevant details. Statistical analyses included frequency-weighted means (FWMs), associated standard deviations, narrative syntheses, and limited meta-analyses, where appropriate. RESULTS: A total of 6 moderate-quality randomized trials were included from 749 screened. Melatonin (3-10 mg) was administered to 227 patients (FWM age=43.3±8.6 years; 46.2% male; BMI=26.6±3.2 kg/m2), placebo to 125 patients (age=43.2±10.1 years; 60% male; BMI=28.5±4.3 kg/m2), and active pharmacologic comparators (fentanyl, gabapentin, dexmedetomidine, zolpidem) to 151 patients (age=46.6±8.9 years; 40.5% male; BMI=26.3±3.5 kg/m2). Procedures primarily involved uncomplicated lumbar laminectomies (1-4 levels), with outcomes assessed up to 24 hours postoperatively. Melatonin was associated with significant improvements in early postoperative VAS-pain scores, blood-pressure-related, analgesic-related, and anxiety-related outcomes versus placebo across most reporting studies. Compared with active pharmacologic agents, significant benefits were observed only in select nausea- and anxiety-related instances. Limited meta-analysis (n=2) demonstrated higher 24-hour VAS-pain for melatonin versus gabapentin, though mean difference was near-negligible and harbored extensive statistical constraints. CONCLUSION: Melatonin demonstrates variable utility following spine surgery, with generally consistent anxiolysis and frequent benefit versus placebo but less consistent and comparatively weaker efficacy relative to active pharmacologic comparators. Future outcome-homogenous studies incorporating more granular, expansive comparator arms and more robust quantitative analyses are needed to further elucidate melatonin's role in advancing spine care. LEVEL OF EVIDENCE: Level II.

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PubMed2026

Human endogenous retroviruses leading to autoimmune diseases.

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and were long regarded as inert remnants of ancestral retroviral infections. Increasing evidence indicates that HERVs are active genomic elements capable of influencing transcriptional programs, modulating immune responses, and contributing to disease pathogenesis. Under physiological conditions, HERV expression is tightly controlled by epigenetic mechanisms; however, infections, chronic inflammation, aging, and diverse environmental stimuli can promote HERV reactivation. HERV-derived RNAs and proteins engage innate immune sensors and trigger antiviral-like responses through mechanisms of viral mimicry, leading to activation of type I interferon and other inflammatory pathways. HERV dysregulation has been associated with disease-relevant immune pathways. This review summarizes recent advances linking HERVs to autoimmune disease pathogenesis and discusses their potential translational relevance as biomarkers and therapeutic targets.

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PubMed2026

Robotic-assisted transbronchial biopsy versus computed tomography-guided transthoracic needle biopsy for peripheral pulmonary lesions: a systematic review and meta-analysis of direct comparative studies.

Robotic-assisted bronchoscopy (RAB) and computed tomography-guided transthoracic biopsy (CTTB) are competing strategies for sampling peripheral pulmonary lesions (PPLs). Whether they differ in yield or safety is uncertain. To our knowledge, this is the first systematic review restricted to direct comparisons. We searched MEDLINE, Europe PMC, Scopus, Web of Science and ClinicalTrials.gov from inception to 7 July 2026 for studies directly comparing RAB with CTTB in adults with PPLs. The primary outcome was strict 2024 American Thoracic Society/American College of Chest Physicians diagnostic yield. Risk of bias was assessed with ROBINS-I and certainty with GRADE. A cohort-genealogy step identified, per outcome, the largest set of cohorts sharing no patients; only that set was pooled, with Hartung-Knapp and Mantel-Haenszel sensitivity analyses. Five retrospective studies from one US health system were eligible. Four share patients; at most three cohorts are mutually independent. Across those three, diagnostic yield was comparable (risk ratio [RR] 0.99, 95% confidence interval [CI] 0.93-1.06; I²=24%; Hartung-Knapp 0.87-1.13), with an identical relative effect under strict and intermediate definitions although absolute yields fell from 88% to 74-84% under strict criteria. Pneumothorax requiring a chest tube and/or admission was about three-quarters less frequent with RAB across all three cohorts (RR 0.25, 95% CI 0.14-0.46; I²=0%; Hartung-Knapp 0.07-0.96). Strict yield (RR 0.99) and any pneumothorax (RR 0.06) were reported by two cohorts each and neither survives the few-studies correction. RAB took about 50 min longer than CTTB where same-session staging endobronchial ultrasound was counted in the robotic time, but only about 8 min longer than CTTB where it was not. Only one cohort reported yield by lesion size category and none reported yield by bronchus sign or lung zone, so lesion-level subgroups could not be pooled. Certainty was low for pleural complications and very low elsewhere. Low-certainty evidence indicates that RAB is associated with fewer pleural complications, with no statistically detectable difference in diagnostic yield; equivalence was not formally established. Because all evidence is retrospective, confined to one health system, and almost never stratified by lesion size or accessibility, these findings are hypothesis-generating and require a multicenter randomized trial.

Humans↗

PubMed2026

Maternal anemia and the risk of preterm birth: a meta-analysis.

BACKGROUND: Globally, preterm birth continues to be a primary contributor to neonatal complications and fatalities. Anemia among the most common nutritional disorders in pregnancy has been proposed as a potential contributor to early delivery. Although extensively studied, the available evidence does not yet provide a clear consensus. This study aimed to conduct a meta-analysis to quantitatively assess the relationship between maternal anemia and the risk of preterm birth. METHODS: This meta-analysis was conducted and reported in accordance with the PRISMA guidelines and the MOOSE checklist. A systematic and exhaustive search was performed across multiple electronic databases PubMed, Scopus, Web of Science, Embase, and the Cochrane Library to identify relevant studies published from inception to 1 January 2025. Effect sizes were combined using a random-effects meta-analysis. RESULTS: A total of 45 articles, reporting 60 independent study populations comprising 2,119,392 pregnant individuals were included. Considerable heterogeneity was found across the included studies (I2 = 95.54%, p < 0.001), which justified the application of a random-effects model for pooling effect sizes. Maternal anemia was significantly associated with an increased risk of preterm birth (pooled odds ratio[OR] = 1.28, 95% confidence interval [CI]: 1.20-1.36, p < 0.001). Despite substantial heterogeneity, sensitivity analyses confirmed the robustness of this association. The relationship was strongest in studies conducted in Asia (OR = 1.30, 95% CI: 1.22-1.40; p < 0.001) and the Europe (OR = 1.24, 95% CI: 1.08-1.41; p = 0.001) and reached statistical significance when anemia was assessed during the first trimester (OR = 1.12, 95% CI: 1.03-1.51; p = 0.007) and the third trimester (OR = 1.65, 95% CI: 1.42-1.91; p < 0.001), while no significant associations were found in the second trimesters (OR = 1.10, 95% CI: 0.99-1.22; p = 0.05). Funnel plot asymmetry and a significant Egger's test (p = 0.001) indicated potential publication bias, although Begg's test was not significant (p = 0.425). CONCLUSIONS: The current evidence suggests that maternal anemia, particularly in the third trimester, is significantly associated with an increased risk of preterm birth. These findings emphasize the clinical imperative for comprehensive and timely anemia screening during the third trimester. Integrating targeted interventions such as iron and micronutrient supplementation, is essential to mitigate the risk of preterm delivery and improve neonatal outcomes.

Humans↗

PubMed2026

Early mobilization within 24 to 48 h improves postoperative clinical outcomes in older adults with hip fracture: A systematic review and meta-analysis.

BACKGROUND: Hip fracture is a major public health concern among older adults, often resulting in prolonged disability, institutionalization, and increased healthcare burden. Early mobilization has been widely recommended to enhance postoperative recovery; however, there is a lack of consolidated evidence quantifying its impact on clinical and functional outcomes. This study aimed to synthesize and evaluate the impact of early mobilization following hip fracture surgery in older adults and to explore potential sources of heterogeneity to better inform clinical and nursing practice. METHODS: A comprehensive literature search was conducted across seven databases (PubMed, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Emcare) from inception to June 15, 2025. Eligible studies included randomized controlled trials and observational cohort studies comparing early mobilization (defined as ambulation within 24 to 48 h postoperatively) to delayed or usual mobilization in patients undergoing hip fracture surgery. Primary outcomes included mortality, discharge destination, and length of hospital stay. Secondary outcomes included postoperative complications, functional recovery, and readmission. Risk of bias was assessed using funnel plots and Egger's test. RESULTS: Twenty-six studies involving 297,435 patients were included. Compared with delayed mobilization, early mobilization significantly reduced 30-day mortality (relative risk = 0.40, 95% confidence interval: 0.25-0.64) and 1-year mortality (relative risk = 0.57, 95% confidence interval: 0.40-0.80) (both p < 0.05). In regional analyses of pooled mortality, similar reductions were observed across Asia-Pacific, North America, and Europe. Patients receiving early mobilization were more likely to be discharged home and had shorter hospital stays. Early mobilization also resulted in a reduced risk of postoperative complications (relative risk = 0.79, 95% confidence interval: 0.74-0.84, p < 0.05), with specific improvements in pneumonia and thromboembolism rates. Functional independence was significantly improved, as shown by higher Barthel Index scores and increased odds of achieving Functional Independence Measure ≥5 at discharge. No significant difference was observed in readmission rates. CONCLUSIONS: lization within 24 to 48 h following hip fracture surgery was associated with favorable outcomes, including reduced mortality, improved functional independence, higher rates of discharge to home, shorter hospital length of stay, and fewer postoperative complications. Although heterogeneity across studies and the predominance of observational evidence warrant cautious interpretation, these findings support current recommendations for early mobilization and highight the potential value of structured and standardized mobilization protocols in routine postoperative hip fracture care.

Humans↗