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PubMed2026

Civil liability in oral & maxillofacial surgery: Α systematic review.

Maxillofacial surgery is a surgical specialty with anatomical, functional, and aesthetic requirements, which makes it a field at increased risk of medical negligence and subsequent legal claims. The review was conducted in accordance with the PRISMA guidelines and used international medical and legal databases. Studies that analyzed court decisions, insurance claims, or recorded compensation data related to maxillofacial surgery were included. The extracted data included, among others, the year and country of publication, the causes of action, and the amounts of financial compensation. Most lawsuits originate from countries with developed medical liability systems, primarily the United States and the United Kingdom, and there has been an increasing trend in publications over the last two decades. The most common causes of lawsuits involve nerve injuries, delayed or incorrect diagnoses, technical errors during surgery, and inadequate informed consent. The amounts of compensation vary widely, from lower five-digit amounts in milder cases to particularly high amounts in cases of permanent functional or aesthetic damage, placing a significant overall financial burden on health systems. Medical negligence in maxillofacial surgery constitutes an important forensic and socioeconomic issue. Understanding the causes of lawsuits and their financial consequences can help improve clinical practice, inform patients, and prevent legal disputes.

Humans↗

PubMed2026

How Following Medical Artificial Intelligence Advice Can Mitigate Malpractice Liability: Cross-National Insights from a Randomized Trial.

Artificial intelligence (AI) increasingly influences clinical decision-making, yet its recommendations may diverge from standard care. Although malpractice concerns are thought to discourage physicians from following AI advice, experimental evidence from the United States suggests the opposite: lay jurors are more likely to hold physicians liable when they reject AI recommendations. Whether this pattern extends to systems in which court-appointed experts, not lay jurors, determine liability remains unknown. Methods: To examine how physicians and laypeople in expert-based and lay-juror legal systems evaluate physicians' acceptance or rejection of AI recommendations, particularly when those recommendations deviate from standard care, we designed a randomized vignette study: a 2 × 2 factorial design varying the AI recommendation (standard vs. nonstandard care) and a fictional physician's decision (accept vs. reject). The study was conducted online in 2023 among nationally representative samples of U.S. and German adults and from 2023 to 2024 among German physicians. In total, 387 German physicians, 2291 U.S. adults, and 2283 German adults participated; those not completing the survey or failing attention checks were excluded per preregistered criteria. Participants were randomly assigned to 1 of 4 vignettes, varying the AI recommendation (standard vs. nonstandard care) and physician's decision (accept vs. reject). The reasonableness of the fictional physician's decision was measured, rated by participants on a Likert scale. Results: Analysis, following preregistered exclusion criteria, included 248 German physicians, 1202 U.S. adults, and 1358 German adults. Physicians accepting standard-care AI recommendations were rated more reasonable than those rejecting them (U.S. laypeople: t = 5.36; 95% CI, 0.45-0.97; P < 0.001; German physicians: t = 2.47; 95% CI, 0.14-1.30; P = 0.02; German laypeople: t = 4.14; 95% CI, 0.27-0.76; P < 0.001). Ratings of physicians accepting versus rejecting AI nonstandard-care recommendations were statistically equivalent. Equivalence was tested at an α-value of 0.05 using a two 1-sided tests procedure, reported with 90% CIs per standard convention (U.S. laypeople: t = -4.90; 90% CI, -0.1 to 0.36; P < 0.001; German physicians: t = -1.76; 90% CI, -0.12 to 0.67; P = 0.04; German laypeople: t = 5.35; 90% CI, -0.35 to 0.06; P < 0.001). Conclusion: Across the United States and Germany, samples representative of lay jurors and court-appointed experts viewed accepting standard-care AI advice as more reasonable, whereas accepting or rejecting nonstandard-care AI advice was judged similarly. Contrary to predictions, malpractice liability regimes do not necessarily pose a barrier to AI use in precision medicine.

Artificial Intelligence↗

PubMed2026

Tele-Oncology in the Post-Pandemic Era: Clinical Integration, Access Disparities and Medico-Legal Accountability.

PURPOSE OF THE REVIEW: Tele-health has evolved from a marginal tool confined to rural populations and selected follow-up programs into a structurally integrated component of modern cancer care. Prior to COVID-19, its adoption was constrained by regulatory fragmentation, non-uniform reimbursement, and licensure barriers. This narrative review evaluates the evolutionary integration of tele-health in oncology post-COVID-19, examines digital disparities across patient populations, and addresses the medico-legal implications of this integration, with the objective of providing a comprehensive and clinically actionable framework for the governance of virtual oncology care. RECENT FINDINGS: The pandemic acted as a global catalyst, driving telehealth to over 50% of oncology outpatient encounters in some settings, before stabilising post-pandemic at approximately 10-20% of consultations within hybrid care models. Evidence supports meaningful clinical benefits - improved access to specialist services, reduced travel burden, and sustained continuity of care - with outcomes comparable to in-person care in postoperative follow-up, symptom monitoring, and survivorship. However, persistent disparities in device availability, connectivity, and digital literacy disproportionately affect older, rural, and socioeconomically disadvantaged patients, raising the risk that geographic inequalities are replaced by technological ones. From a medico-legal standpoint, the remote modality does not modify the applicable standard of care, yet restricted physical examination and reliance on patient-reported data introduce risks of diagnostic delay and incomplete clinical assessment, with direct implications for professional liability, data protection under HIPAA and GDPR, cross-border licensure, and multi-party accountability across physicians, institutions, and technology providers. Tele-oncology has become a permanent structural feature of modern cancer care, offering demonstrable benefits in access, continuity, and patient satisfaction. Yet its integration has been uneven, its governance remains fragmented, and its medico-legal landscape is still evolving. Realising the full potential of virtual oncology care - equitably and safely - requires coherent regulatory frameworks, sustained investment in digital infrastructure, and explicit attention to the populations at greatest risk of being left behind.

Humans↗

PubMed2026

Alcohol use disorder and childhood adversity in the association between polygenic risk and suicidality.

OBJECTIVE: Suicidal ideation (SI) and suicide attempt (SA) are both influenced by genetic, behavioral, and environmental factors. Alcohol use disorder (AUD) and adverse childhood experiences (ACEs) may mediate or moderate the effects of genetic liability for suicidality. METHODS: Using data from 10,275 participants (43.8% female; 47.2% African-like genetic ancestry [AFR], 52.8% European-like genetic ancestry [EUR]), we tested whether polygenic scores (PGS) for SI and SA predicted lifetime suicidality outcomes. We evaluated whether AUD partially accounted for these associations and ACEs moderated the direct and indirect associations. RESULTS: The SA PGS was significantly associated with SA (AFR: b = 0.36, SE = 0.01; EUR: b = 0.17, SE = 0.01; both ps < 2e-16), but the SI PGS was not associated with SI (p > 0.55). AUD statistically mediated the association between the SA PGS and SA, accounting for approximately 2% of the total association in AFR individuals and 10% in EUR individuals (both ps < 2e-16). Notably, the proportion of the association that was accounted for by AUD decreased as ACEs exposure increased, from 4.30% to 0.54% in AFR individuals and from 13.31% to 3.44% in EUR individuals. In contrast, there was only very modest mediation and no moderated mediation for SI. CONCLUSIONS: Particularly among individuals with lower ACEs exposure, AUD accounted for a meaningful proportion of the association between genetic liability to SA and lifetime SA. These findings highlight different correlates across suicidality phenotypes and suggest potential clinical relevance for AUD in the association between genetic liability and SA.

Adult↗

PubMed2026

Integrative multi-omics reveals a fibroblast-centered, ZFHX3-prioritized regulatory framework linking sick sinus syndrome and atrial fibrillation.

OBJECTIVE: To define shared genetic and multi-scale mechanisms underlying comorbidity between sick sinus syndrome (SSS) and atrial fibrillation (AF). METHODS: We integrated genome-wide association study (GWAS) summary statistics for SSS and AF with Genotype-Tissue Expression (GTEx) expression and splicing quantitative trait loci (eQTL/sQTL), atrial single-cell and spatial transcriptomics, and epigenomics. We identified trait-relevant tissues and pathways, prioritized shared cell types, quantified genome-wide and local genetic sharing, detected joint loci by cross-trait meta-analysis, and linked loci to regulatory programs via colocalization and cell-prioritized co-expression networks. RESULTS: Both traits showed strongest enrichment in cardiac tissue, especially Heart Atrial Appendage. Fibroblasts from the left atrial appendage were consistently prioritized as the key shared cell population. SSS and AF displayed significant positive genome-wide genetic correlation, with multiple locally shared regions, including six major loci. Cross-trait meta-analysis identified eight joint-phenotype SNPs implicating four susceptibility genes. ZFHX3 was the leading tissue-cell-gene candidate, acting as a hub in fibroblast co-expression modules and colocalizing with cardiac regulatory signals. CONCLUSION: Shared liability for SSS and AF is highly tissue- and cell-specific, converging on regulatory networks in atrial appendage fibroblasts, with ZFHX3 serving as a central mechanistic and biomarker node.

Humans↗

PubMed2026

Mendelian randomisation for rheumatology: beyond hype-what it's good for, what it can't do, and how to read it critically.

Mendelian randomisation (MR) has become abundant in the literature, with variation in quality and frequent overinterpretation of causality. This creates a problem for clinical readers, reviewers, and editors: some MR studies can sharpen causal thinking, prioritise drug targets, and challenge misleading observational claims, whereas others are little more than automated exposure-outcome scans with causal claims disproportionate to the evidence. MR can strengthen causal inference when randomised trials are impractical and conventional observational studies are vulnerable to confounding, reverse causation, or selection bias. In rheumatology, credible MR can contribute to questions about disease aetiology, modifiable risk factors, therapeutic target validation, adverse-effect anticipation, and phenotype validation. However, its interpretation depends on whether the exposure is plausibly instrumentable, whether the genetic instruments are biologically defensible, whether assumptions are interrogated in ways appropriate to the design, and whether findings are triangulated with clinical, observational, experimental, and mechanistic evidence. Instead of recapitulating all methodological issues of MR, this review aims to help rheumatologists distinguish robust MR from weak or overinterpreted analyses quickly. We provide an accessible framework for reading and triaging MR studies in rheumatology. Papers that use poorly justified instruments, treat medication use as drug-target evidence, interpret genetic liability as diagnosis, rely on mechanical sensitivity analyses, ignore prior evidence or ask no clinically meaningful question can often be passed over by readers. The goal is not to discourage MR in rheumatology, but to raise the standard; useful MR should clarify causal reasoning rather than simply generate another statistically significant association.

Journal Article↗

PubMed2026

Shared genetic architecture and cellular convergence between female reproductive disorders and pulmonary function: a genome-wide cross-trait analysis.

Female reproductive disorders (FRDs), including polycystic ovary syndrome, endometriosis, uterine leiomyomata, and infertility, have been epidemiologically associated with impaired pulmonary function. However, it remains unclear whether this cross-organ link reflects shared genetic etiology and, if so, which cellular mechanisms mediate it. We performed a systematic genome-wide cross-trait analysis of three FRDs and lung function traits (FEV₁, FVC, FEV₁/FVC) using GWAS summary statistics from individuals of European ancestry, integrating genetic correlation, bidirectional causal inference, pleiotropy mapping, and single-cell enrichment analyses. We identified significant negative genetic correlations between FRDs and lung volume traits, most prominently for FVC (rg range: - 0.077 to - 0.178). Bidirectional causal analyses indicated that FRDs have a detrimental effect on lung volume, with higher FRD genetic liability associated with reduced lung volume. Cross-trait meta-analysis identified 17 pleiotropic variants across 11 loci, with the 19q13.2 (LTBP4) and 12q13.13 (HOXC6/HOXC9) loci showing strong evidence of shared causal variants. Critically, single-cell analyses revealed that shared genetic risk converged on mesenchymal lineages across organs, specifically alveolar adventitial fibroblasts in the lung and stromal/smooth muscle cells in the endometrium. Transcriptome-wide analyses further nominated the estrogen-responsive gene RERG as a convergent gene linking these conditions with lung function. Our study revealed a shared genetic architecture between female reproductive disorders and lung function traits, providing a basis for further mechanistic investigations and potential clinical evaluation. Furthermore, our findings suggest that shared fibroproliferative and hormone-responsive pathways may offer insights into the biological mechanisms underlying these conditions.

Female↗

PubMed2026

Polygenic risk scores in major depressive disorder: A systematic review across diagnostic, treatment, course/severity, and subtype domains.

BACKGROUND: Major depressive disorder (MDD) is heterogeneous across diagnostic, treatment-related, course/severity, and subtype domains. Polygenic risk score (PRS) studies have examined these domains, but differences in PRS sources, samples, methods, and endpoint definitions have fragmented the evidence. We synthesised findings and examined potential contributors to heterogeneity. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and Web of Science were searched for studies published from January 2016 through 25 November 2025. Result records were synthesised using SWiM, and certainty was assessed with an adapted GRADE framework. RESULTS: Sixty studies contributed 493 retained records; 450 were descriptively classified as positive, null, or reverse, although records were not independent. Positive findings accounted for 44/56 diagnostic, 61/273 treatment-related, 64/100 course/severity, and 14/21 subtype records. For MDD/depression-derived PRSs and case-control MDD status, all 10 contributing studies showed higher liability in cases (exploratory exact sign test p = 0.002; FDR q = 0.004). The same PRS group showed positive findings for overall depressive symptom severity (14/18), although the study-level test was imprecise (5/5 studies; p = 0.063). Pharmacological response/remission findings for these PRSs were mostly null or directionally mixed (10 positive, 18 null, and 9 reverse). Treatment-resistant depression (TRD) findings differed by operational definition. Atypical and psychotic subtype signals arose mainly from single-study PRS and endpoint contrasts. CONCLUSIONS: PRS evidence was clearest for MDD diagnostic status and showed a tentative pattern for overall symptom burden. Treatment and subtype findings were less consistent or less replicated. Larger, ancestrally diverse studies with standardised endpoints and transparent PRS methods are needed.

Humans↗

PubMed2026

Utility of monocyte-derived cells to investigate immune-mediated drug-induced liver injury.

Immune-mediated drug-induced liver injury (DILI) is triggered or exacerbated by the immune system mounting an attack against the drug or its metabolites. The array of in vitro assays for evaluating drug immune liability is limited, highlighting a significant gap in effectively predicting and understanding immune-mediated hepatotoxicity. We aimed to investigate whether monocytes differentiated with the Metaheps (MH) protocol could provide insights into the molecular mechanisms of immune-mediated DILI. MH were generated from monocytes of healthy volunteers (HV) and DILI patients. MH phenotypic characterization was performed by proteomics and qPCR. MH sensitivity to drugs associated with immune-mediated DILI was assessed by lactate dehydrogenase (LDH) assay. Drug-induced LDH release by DILI-derived MH was compared to the upper limit of the 95% CI calculated from HV-derived MH cells treated with the same drug. The 95% CI determined in HV-derived MH was set as the sensitivity threshold for the specific drug. MH cells retain the expression of several immune-related proteins of the parental monocytes and activate a pro-inflammatory response upon exposure to lipopolysaccharide. For all MH (6 out of 6) generated from patients with penicillin-induced DILI, the LDH release upon re-challenge was above the threshold. The sensitivity of MH generated from seven patients with immune checkpoint inhibitor (ICI)-induced hepatotoxicity was ICI-dependent, responding to nivolumab and/or ipilimumab (4 out of 5), but not to pembrolizumab (0 out of 2). Additionally, DILI-derived MH were not sensitive to non-DILI drugs. In conclusion, monocyte-derived cells may serve as an additional tool for drug-specific mechanistic studies of immune-mediated DILI.

Humans↗

PubMed2026

Patterns and implications of co-use between vaping and hallucinogens: a systematic review and meta-analysis.

BACKGROUND: The co-occurrence use of e-cigarettes and hallucinogens has become increasingly common, particularly among youth and young adults. However, evidence regarding the association between these behaviors remains limited and fragmented. This systematic review and meta-analysis aimed to synthesize current evidence, examining the correlation between hallucinogen use and the likelihood of being an e-cigarette user. METHODS: A comprehensive search was conducted in PubMed, Scopus, Web of Science, EMBASE, and Cochrane CENTRAL up to June 2025. Eligible studies measured both hallucinogen and e-cigarette use and reported quantitative associations between these behaviors. Data extraction and risk-of-bias assessments were performed independently by three reviewers using the Newcastle-Ottawa Scale. Pooled effect sizes were calculated using a random-effects model (REML). Certainty of evidence was evaluated with the GRADE approach. RESULTS: Eleven studies met the inclusion criteria (n = 247,904), and seven were included in the meta-analysis (n = 217,478). The pooled analysis demonstrated that hallucinogen users had 4.47 times higher odds of being e-cigarette users (OR: 4.47, 95% CI 2.72 to 7.34; p < 0.001; I2 = 95.7%, n = 7). The certainty of evidence was rated as low. CONCLUSIONS: Hallucinogen use is directionally and strongly associated with e-cigarette use across diverse populations. Although the direction of association was consistent across studies, the magnitude of effect was heterogeneous. These behaviors likely share psychosocial and environmental determinants, although alternative explanations, including shared genetic liability, recall bias, and residual confounding, cannot be excluded. Further longitudinal studies are needed to clarify the underlying mechanisms of this association and establish temporality. The findings also support integrating hallucinogen-use screening into e-cigarette prevention and harm-reduction programs targeting youth and young adults.

Humans↗