Topical and oral retinoids are widely used in dermatology for acne and photoaging. Concern regarding a possible increase in all-cause mortality emerged after the VA Topical Tretinoin Chemoprevention Trial reported excess deaths among older patients receiving high-potency topical tretinoin. Subsequent analyses reinforced this signal, leading to caution in prescribing high-strength topical retinoids despite limited confirmatory data in younger acne populations. A retrospective cohort study was conducted using the TriNetX Research Network. Two propensity score matched analyses compared acne patients treated with oral isotretinoin or topical tretinoin 0.1% with acne patients without retinoid exposure. Cohorts were matched 1 to 1 using demographic and clinical covariates. The primary outcome was all-cause mortality. Risk-based and time-to-event analyses were performed. After matching, 13,891 isotretinoin users and 8,070 topical tretinoin users were analyzed alongside matched controls. Oral isotretinoin was associated with a lower absolute mortality risk compared with controls, although no significant difference was observed in time-to-event analysis. Topical tretinoin showed no difference in mortality risk or survival. Subgroup analyses stratified by age and sex demonstrated no increased mortality risk. Neither oral isotretinoin nor high-potency topical tretinoin was associated with increased all-cause mortality in acne patients. These findings provide reassurance for clinicians prescribing retinoids in routine dermatologic care.
Patients with chronic kidney disease (CKD) and dialysis dependence represent high-risk populations with increased demand for total joint arthroplasty (TJA). We aimed to assess surgical outcomes of CKD and dialysis-dependent (DD) patients undergoing TJA. A multicenter retrospective review of TJA records between June 2011 and July 2022 was conducted. Patients with a diagnosis of CKD who were DD at the time of surgery were propensity-matched to non-DD CKD patients and control subjects without CKD in a ratio of 1:5:5. Matched comparisons and Kaplan-Meier survival analyses were conducted for a total of 176 (DD: 16) total knee arthroplasty (TKA) and 297 (DD: 27) total hip arthroplasty (THA) patients. Medical complications within 90 days after both TKA (control: n = 1, 1.3%; CKD: n = 3, 3.8%; DD: n = 3, 18.8%; P = 0.005) and THA (control: n = 4, 3%; CKD: n = 4, 3%; DD: n = 6, 22.2%; P < 0.001) were significantly higher in the DD group. Infection and revision rates at last follow-up were similar between the three groups after TKA (P > 0.05) and THA (P > 0.05). In Kaplan-Meier analyses, survivorship free of mortality was lowest in the DD group after THA at 40.3% compared with 100% in the control and 78.8% in the CKD groups (P < 0.001). Dialysis-dependent patients are at an increased risk of postoperative medical complications and mortality compared with matched groups with and without CKD. Infection and revision rates seem to be similar. We advocate for a shared decision-making approach between patient and surgeon to include a thorough discussion weighing postoperative complication risk, patient function, and life expectancy. III.
Total shoulder arthroplasty (TSA) has experienced rapid growth. Yet graduating orthopaedic surgery resident (GOSR) TSA volumes are not individually reported due to its exclusion from the Accreditation Council for Graduate Medical Education (ACGME) case minimum list. Rather, TSAs are grouped within the shoulder repair/revision/reconstruction (RRR) category. This study evaluated long-term trends and identified disparities in GOSR shoulder case volumes since the inception of case minimums in 2013. Publicly available ACGME case logs of 8247 GOSRs were analyzed from 2014 to 2024. Average case volumes were compared between 2014 and 2024. Trends in case volume differences between the 10th and 90th percentile GOSRs were assessed. Changes in the proportions of each procedure category relative to overall shoulder procedures were analyzed. GOSRs performed more shoulder RRR and overall shoulder cases in 2024 than in 2014 (RRR: 46.4 vs. 24.2 cases [+91.7%]; overall: 174.9 vs. 125.9 cases [+38.9%]; P < 0.001). Differences in shoulder RRR and overall shoulder procedures between the 10th and 90th percentiles increased year-over-year (+2.86 and +5.11 cases/year, respectively; P < 0.001), with the gap between percentile groups demonstrating consistent expansion (RRR: ρ = 0.975; overall: ρ = 0.961; P < 0.001). Relative to overall shoulder procedures, the proportion of shoulder RRRs increased from 2014 to 2024 (19.2% to 26.5%, P = 0.045). Although average GOSR shoulder case volumes increased over the long term, interresident disparities widened. Shoulder RRRs expanded to more than one fourth of resident shoulder procedures, paralleling TSA growth nationally. Residency governance bodies should consider implementing a resident TSA case minimum to ensure experience in this important procedure.
Eosinophil esophagitis (EoE) shares many epidemiologic and pathophysiologic characteristics with other allergic diseases, especially allergic asthma. Since rhinovirus (RV) infection is known to contribute to inflammation in allergic asthma, we sought to investigate whether RV might also contribute to esophageal inflammation in EoE through epithelial activation. In vitro cultures of primary esophageal epithelial cells and a human non-transformed immortalized esophageal epithelial cell line (EPC2-hTERT) grown submerged or at air-liquid interface (ALI) were infected with RV-A1a or RV-A16. In addition, we added Interleukin (IL)-13 to mimic EoE conditions. RV-binding receptors, RV replication, and interferon lambda-1 (IFNL1) response to infection were measured. RNA-Sequencing (RNA-Seq) on RV-infected EPC2-hTERT cultures was performed for gene ontology analysis and compared to published RNA-Seq data of esophageal biopsies from EoE patients. Both RV receptors were expressed by esophageal cells. After infection, we observed higher RV viral gene expression, indicative of active replication. IL-13 had little effect on replication in monolayers but was required in ALI for replication to occur. IFNL1 mRNA was induced by RV-A1a in both cell types and IFNL1 protein was increased in IL-13-treated EPC2-hTERT monolayers. Gene ontology analysis of our in vitro experimental model highlighted virus-induced processes and increased interferon activity. In addition, we found overlapping genes between our RNA-Seq results of EPC2-hTERT cells and publicly available RNA-Seq data from esophageal biopsies of patients with EoE versus healthy control donors. Our data suggest the possibility that viruses such as RV may contribute to esophageal inflammation and play an important role in the inception and/or persistence of EoE.
Coeliac Disease (CeD) is a chronic gastrointestinal inflammatory disease initiated by dietary gluten in genetically predisposed individuals. While the inflammatory processes which drive tissue destruction in the coeliac duodenum have been extensively characterised, an increased oxidative stress (OS) response has also been suggested to contribute to CeD pathogenesis. However, the precise mechanisms which regulate OS in the coeliac mucosa and whether they impact inflammation remain ill defined. The master anti-oxidant transcriptional regulator Nuclear factor erythroid 2-related factor 2 (Nrf2), and its inhibitor, Kelch like ECH-associated protein 1 (Keap1) have been implicated in chronic gastrointestinal inflammatory diseases, such as ulcerative colitis but have been largely unexplored in the context of CeD. To investigate redox balance in the CeD duodenum, we utilised single cell transcriptomics to assess overall OS and cytoprotective Nrf2 activation across cell subsets in duodenal biopsies from CeD patients. OS induced gene expression was broadly increased across multiple cell subsets in the CeD mucosa. Simultaneously, specific markers of Nrf2 activation were decreased in cell subtypes central to pathogenesis of CeD, including activated CD4+ T cells and intraepithelial T lymphocytes, indicating a distinct redox imbalance in these cells. Furthermore, pharmacological activation of Nrf2 significantly decreased gliadin induced IFNG expression in CeD duodenal biopsies. Taken together, our findings demonstrate that redox imbalance represents a therapeutic opportunity for the modulation of proinflammatory responses that drive the pathogenesis of CeD.
Malignant brain tumours have a poor prognosis. Most people would prefer to die in their own home, rather than in a hospital or other settings. We aim to examine predictors of the place of death for adult patients with malignant brain tumours in England. This is a retrospective cohort study. We examined factors associated with death at home using logistic regression. We included adult patients diagnosed with a malignant brain tumour between 2013 and 2018 from England's national cancer registry data (N = 20,598). Our dependent variable was place of death (home/not home) and our independent variables were sex, age, region, tumour type, deprivation index, line of treatment, treatment close to death, and interval between diagnosis and death. The analysis revealed that receiving treatment during the last 3 months had the most substantial effect, with a significant decrease of 38% in the odds of dying at home, while having received one line of treatment increased the odds of dying at home by 21%. Following this, residing in the West Midlands or London was associated with a notable decrease of 20% and 7%, respectively, in the odds of dying at home compared to the South East. Other factors that influenced the likelihood of dying at home included being female, which increased the odds by 2%, whereas living in a deprived area (fourth quintile) decreased the odds by 13%. Furthermore, being diagnosed with glioblastoma (GBM) was associated with 7% higher odds of dying at home. Finally, for one unit of change (day) in the interval between diagnosis and death, the odds of dying at home increases by a factor of 1.09. For one unit of change (year) in the variable age, the odds of dying at home increases by a factor of 1.05. We have presented the first ever national study of place of death and predictors of this for patients with malignant brain tumours in England. Patients with malignant brain tumours are more likely to die at home than the general population; however, this effect is most marked in patients with GBM. Having treatment within the last 3 months of life, living longer post diagnosis, and geographical region also influenced the change of dying at home. This work provides an essential baseline comprehensive national report on place of death for a large national cohort with a poor prognosis.
The aim of this study was to determine whether early symptom cluster composition at presentation predicts recovery after sport-related concussion, and whether these associations differ by concussion history. The authors conducted a retrospective cohort study of athletes aged 12-22 years who were evaluated at their regional concussion center between November 2017 and April 2022. Cluster ratios for cognitive, somatic, and emotional symptoms were calculated as domain sums divided by the initial Post-Concussion Symptom Scale (PCSS) score. Primary outcomes were the number of days to return to learn (RTL), symptom resolution (SR), and return to play (RTP). Multivariable linear regression models were fit separately for athletes with no prior concussion and for those with ≥ 1 prior concussion, entering all three cluster ratios and adjusting for age, sex, time to presentation, and a history of attention-deficit/hyperactivity disorder, migraine, and psychiatric conditions. Effect modification was assessed using a hierarchical full-cohort model that included a cognitive ratio × number of prior concussions interaction term. Kaplan-Meier curves were used to assess recovery across strata defined by prior concussion (yes/no) and high versus low cognitive burden (median split), with groups compared using log-rank tests. Of 2086 screened patients, 476 met the inclusion criteria (58.4% with no prior concussion and 41.6% with ≥ 1 prior concussion). Athletes with prior concussion were older (mean age 16.43 ± 1.92 vs 15.67 ± 1.55 years, p < 0.001), more often White (87.8% vs 76.3%, p = 0.011), presented later (mean 3.59 ± 3.34 days vs 2.86 ± 3.13 days, p = 0.016), and had similar initial PCSS scores (mean 29.39 ± 22.07 vs 28.32 ± 22.82, p = 0.607), but longer RTP (mean 33.40 ± 24.46 days vs 27.50 ± 22.34 days, p = 0.017). In multivariable models, symptom cluster ratios were not associated with RTL, SR, or RTP in the no prior concussion group. In the prior concussion group, a higher cognitive cluster ratio was associated with longer RTL (p = 0.020) and independently predicted longer SR (p = 0.003). In whole-cohort models, the interaction between cognitive ratio and prior concussion was significant for SR (p = 0.005), indicating that the adverse impact of cognitive-dominant profiles on recovery increased with the number of prior concussions. Kaplan-Meier analyses showed stepwise delays in RTL, SR, and RTP across cognitive burden-prior concussion strata (SR: log-rank χ2(3) = 10.62, p = 0.014; RTP: χ2(3) = 10.48, p = 0.015; RTL: χ2(3) = 8.10, p = 0.044), with the slowest recovery demonstrated in the group with prior concussion and high cognitive burden. Symptom composition at presentation is prognostic primarily in athletes with prior concussion. Cognitive-dominant profiles predicted slower SR and RTL in this subgroup, and the adverse effect of cognitive burden on recovery increased with increasing concussion history.
Procedures have traditionally been delayed 6 to 12 months after isotretinoin because of concerns about abnormal scarring; evidence for fractional ablative CO2 laser is limited in higher Fitzpatrick skin types. To assess the safety and effectiveness of ablative fractional CO2 laser (AFCL) for atrophic acne scars during and after oral isotretinoin. This was a single-center retrospective cohort of 106 patients (188 AFCL sessions) grouped as concurrent isotretinoin, ≤90 days since discontinuation, 91 to 180 days, or >180 days (control). Outcomes included abnormal scarring, delayed re-epithelialization (>14 days), postinflammatory hyperpigmentation (PIH) at 1 and 3 months, and scar-score change. Overall group comparisons and adjusted patient-level and session-level models were performed. Abnormal scarring occurred in 3/106 patients (2.8%) with no significant between-group difference (p = .762). Delayed re-epithelialization >14 days occurred in 11/106 patients (10.4%) and was numerically highest in the concurrent isotretinoin group (6/31 [19.4%]); however, the overall four-group comparison was not significant (p = .243), and concurrent isotretinoin was not statistically significant in an adjusted session-level generalized estimating equation model (OR: 4.79, 95% confidence interval: 0.79-29.13; p = .089). PIH at 3 months was higher in the ≤90-day group versus controls (adjusted OR: 6.03, 95% confidence interval: 1.55-23.52; p = .010). Concurrent isotretinoin was not associated with increased PIH or abnormal scarring. Higher density predicted delayed re-epithelialization. AFCL during low-dose isotretinoin or within 6 months after isotretinoin discontinuation was not associated with increased abnormal scarring. Because delayed re-epithelialization was numerically more frequent during concurrent isotretinoin and density was associated with slower healing, conservative density selection and careful counseling remain appropriate. PIH risk was elevated when treatment occurred within 90 days after discontinuation.
Retrospective radiographic study of a multicentric prospective database. This study aimed to analyze lumbar lordosis (LL) proximal and distal arcs relationships with spinopelvic parameters and determine how their distribution varies with pelvic incidence (PI). LL is a key component of sagittal spinal alignment, yet its definition and assessment remain debated. Recent evidence suggests LL is not a uniform curvature but a complex structure with proximal and distal arcs exhibiting possibly distinct biomechanical roles. This study included 642 healthy volunteers (mean age: 37.6±16.3) with full-body stereoradiographs, without spinal deformities. Maximum LL was assessed (LLmax), measured between thoracolumbar inflexion vertebra upper endplate and sacral plateau. Correlations between proximal lordosis (LLprox, measured between thoracolumbar inflexion vertebra upper endplate and lumbar apex upper endplate), distal lordosis (LLdist, measured between lumbar apex upper endplate and sacral plateau) and spinopelvic parameters were sought. Subjects were stratified into five PI groups to determine lordosis distribution variation with PI regarding angle and number of vertebrae included in curvature. LLdist strongly correlated with pelvic parameters, particularly sacral slope (SS, r=-0.83, P<0.001) and PI (r=-0.54, P<0.001), but not with thoracic alignment. LLprox correlated with both pelvic and thoracic parameters, including SS (r=-0.31, P<0.001) and thoracic kyphosis (r=-0.35, P<0.001). As PI increased, the contribution of LLdist to LLmax rose from 55±12% to 66±8% (P<0.001), while the number of vertebrae in the distal arc increased from 1.52±0.50 to 2.32±0.59 (P<0.001). Consequently, LLprox's proportional contribution to LLmax decreased, despite a stable vertebral extent. LL comprises two functionally distinct arcs: a pelvic-driven distal arc and a proximal arc influenced by overlying alignment and pelvic parameters. As PI increases, LL distal arc becomes preponderant. These findings advocate for a segmental approach in clinical assessment and surgical planning, emphasizing the need to consider both arcs independently. 3.
Pancreatitis and pancreatic cancer lead to excess mortality in the general population. Excessive intrapancreatic fat deposition (IPFD) is a common driver of diseases of the exocrine pancreas according to the PANDORA hypothesis. However, the relationship of IPFD with mortality has never been investigated. We aimed to explore the association of IPFD with mortality. Participants from the UK Biobank were divided into two cohorts based on the availability of IPFD quantified using MRI. The Kaplan-Meier survival analysis and multivariable Cox-proportional hazard model were used. Genome-wide association study (GWAS) on IPFD and Mendelian randomization analysis were performed. An IPFD-linked polygenic risk score (PRS) was applied in the MRI-naïve cohort. A total of 55,058 participants were analyzed, 695(1.26%) of whom died during a median follow-up of 4.9 years. Excessive baseline IPFD was significantly associated with an increased risk of all-cause mortality (HR=1.081, p<0.05) and mortality from vascular diseases (HR=1.247, p<0.001). GWAS identified 38 significant IPFD-associated SNPs. The PRS derived from these SNPs showed significant associations with all-cause mortality and mortality from vascular diseases. In the MRI-naïve cohort of 354,761 participants, consistent results were obtained using the PRS as a genetic proxy for IPFD. Excessive IPFD is associated with elevated risk of future mortality especially from vascular diseases in the general population.
This study investigates the enhanced efficacy of photoinduced microbial inactivation targeting both planktonic and biofilm forms of Gram-negative bacteria, specifically Acinetobacter baumannii and Proteus mirabilis. The approach utilizes diaminocyclohexane (DACH)-based diamines to augment antibacterial photodynamic therapy (aPDT) employing 5-aminolevulinic acid. Results demonstrated that blue light irradiation produced the highest bactericidal effects, achieving mortality rates of 99.9990 ± 0.0008% for P. mirabilis and 99.990 ± 0.001% for A. baumannii at a light dose of 70 J·cm-2 in the presence of a non-cytotoxic concentration of (1R,2R)-N,N'-bis([1,1'-biphenyl]-4-ylmethyl)cyclohexane-1,2-diamine. The biofilm destruction efficiency was suboptimal, with maximum bactericidal efficiencies of 87.1 ± 0.1% and 73.1 ± 0.2% for P. mirabilis and A. baumannii, respectively, after exposure to blue light at a dose of 93.5 J·cm-2. Increased accumulation of protoporphyrin IX within bacterial cells was identified as a key factor contributing to the enhanced photobiocidal efficacy. Additionally, molecular docking analysis was employed to explore potential structural insights into the biological activity of this cyclohexane-1,2-diamine-based ligand. Computational simulations suggested that the ligand could plausibly accommodate within the protoporphyrin IX binding pocket of the modeled ferrochelatase, indicating a potential binding mode compatible with the catalytic cavity.
Cold stress is a major environmental constraint limiting crop productivity and quality. Here, we identify a transcription factor MdGeBP3 in apple, which responds to cold stress at both transcriptional and post-translational levels. Functional analysis revealed that overexpression of MdGeBP3 significantly enhances cold tolerance in both apple calli and the model plant Arabidopsis, and the transcript levels of cold-responsive genes were induced in MdGeBP3 overexpression plants. Furthermore, MdGeBP3 was found to participate in anthocyanin biosynthesis. Overexpression of MdGeBP3 in Arabidopsis and apple calli promoted anthocyanin accumulation. Moreover, temporary overexpression of MdGeBP3 in both apple leaves and fruit peel led to increased anthocyanin accumulation, while silencing the MdGeBP3 gene via a virus-induced method decreased anthocyanin content. Collectively, these findings demonstrate that MdGeBP3 acts as a positive regulator of cold tolerance and anthocyanin biosynthesis, providing new insights into the coordination between stress responses and secondary metabolism in apple.
To evaluate longitudinal trends in gender and regional equity in membership and governance representation within the European Society of Gynaecological Oncology and the European Network of Young Gynaecological Oncologists. We analyzed European Society of Gynaecological Oncology and European Network of Young Gynaecological Oncologists membership and governance data from 2013 to 2024. Descriptive analyses were supplemented with multi-variable logistic regression models to identify predictors of female membership and European Society of Gynaecological Oncology Council representation, including European Network of Young Gynaecological Oncologists status, calendar year or Council term, and United Nations geographic region. European Society of Gynaecological Oncology and European Network of Young Gynaecological Oncologists membership increased from 1588 members in 2013 to 3385 in 2024, and female members reached parity by 2024. Female membership was associated with European Network of Young Gynaecological Oncologists participation (odds ratio 1.82, 95% confidence interval 1.73 to 1.91, p <.001) and calendar year (odds ratio 1.04 per year, 95% confidence interval 1.03 to 1.05, p <.001). Compared with Western Europe, female membership was higher in Northern Europe (odds ratio 1.69, 95% confidence interval 1.55 to 1.84, p <.001) and lower in Eastern Europe (odds ratio 0.78, 95% confidence interval 0.71 to 0.85, p <.001) and non-European regions (odds ratio 0.80, 95% confidence interval 0.74 to 0.86, p <.001). Gender was not associated with Council membership (odds ratio 0.95, 95% confidence interval 0.63 to 1.42, p =.79), and no independent temporal trend was observed (odds ratio 0.91 per term, 95% confidence interval 0.81 to 1.03, p =.13). Geographic variation was evident, with lower odds of Council representation in Eastern Europe (odds ratio 0.54, 95% confidence interval 0.28 to 0.98, p =.05), while estimates for non-European regions were unstable because of sparse representation. European Society of Gynaecological Oncology and European Network of Young Gynaecological Oncologists have made substantial progress toward gender equity at the membership level, largely through early-career engagement. Governance representation appears to be influenced more by geographic and structural factors than by gender, highlighting the need for equity-focused strategies that sustain gender-balanced leadership development while addressing regional disparities.
Posterior or transforaminal lumbar interbody fusion (PLIF/TLIF) has become the standard procedure for treating degenerative lumbar diseases. With the increasing number of surgeries, adjacent segment disease (ASD) is becoming widely known as a postoperative complication. However, the association between lumbosacral sagittal alignment and ASD following L4-5 isolated fusion surgery has not been fully elucidated. The aim of this study was to identify the preoperative radiological risk factors for L3-4 ASD and L5-S1 ASD independently after isolated L4-5 PLIF/TLIF. The authors retrospectively reviewed the data of 151 patients with degenerative lumbar diseases who underwent isolated L4-5 PLIF/TLIF at their institution between April 2013 and August 2022. L3-4 ASD and L5-S1 ASD were evaluated separately, and these groups were compared with the non-ASD group. Radiological ASD was defined as disc height (DH) loss (> 3 mm), posterior opening (> 5°) on flexion, or progression of slippage (> 3 mm) as observed on plane radiographs. Symptomatic ASD was defined as the presence of symptoms attributable to the adjacent segment that required revision surgery within 2 years. Preoperative lumbosacral parameters, including slippage at L4-5 (Meyerding grade), pelvic tilt, sacral slope, pelvic incidence (PI), lumbar lordosis (LL), PI-LL, L1 sagittal vertical axis (SVA), and L4 SVA, were measured using standing radiographs. Intraoperative distraction at the L4-5 DH, preoperative disc degeneration (Pfirrman grade), vacuum phenomenon, foraminal stenosis, and additional decompression at adjacent segments were also evaluated. Of 151 unique patients, 31 (20.5%) had ASD, with 20 (13.2%) included in the L3-4 ASD group and 13 (8.6%) included in the L5-S1 ASD group (2 patients were included in both groups). Multivariate analysis revealed that additional L3-4 decompression and distraction at L4-5 DH were significantly associated with L3-4 ASD, whereas L1 SVA > L4 SVA (L1 plumb line anterior to the L4 plumb line) was associated with L5-S1 ASD. The risk of L5-S1 ASD increased by a factor of 4.13 (p = 0.004) in patients with sagittal imbalance, as indicated by L1 SVA > L4 SVA. These findings suggest distinct characteristics between L3-4 ASD and L5-S1 ASD. L3-4 ASD was not associated with lumbosacral sagittal imbalance. By contrast, an anterior shift of the lumbar loading axis, as indicated by L1 SVA > L4 SVA, was associated with the development of L5-S1 ASD. Preoperative L1 SVA > L4 SVA might serve as a convenient predictive parameter for L5-S1 ASD after isolated L4-5 fusion surgery.
Clinicians spend a substantial share of their working hours on documentation, contributing to workflow inefficiencies, reduced patient-facing time, and increased burnout. Artificial intelligence (AI) medical scribes have emerged as a promising solution to reduce this burden, yet real-world evidence remains limited and heterogeneous, and data from European health systems are especially scarce. This evaluation combines 2 complementary data sources: objective editing metadata from 236,153 notes generated by 1295 clinicians, describing operational editing behavior within the AI medical scribe, and paired self-reported survey responses from 177 fully onboarded clinicians, capturing perceived change in documentation time and clinician experience. This study aimed to evaluate the association of an AI medical scribe on documentation time and clinician experience. This observational real-world evaluation was conducted between April 26, 2024, and October 27, 2025, using retrospective paired ratings. The study was carried out across multiple specialties in primary, secondary, and hospital care within Capio Ramsay Santé, a large integrated health care provider operating in Sweden. Eligibility was limited to fully onboarded users, defined as clinicians who had used the scribe for at least 3 months, created more than 100 notes, generated at least 1 document or certificate, and used the conversational edit ("Add or adjust") feature at least once. Following the introduction of the AI medical scribe, the estimated time spent on documentation per note was lower than before (4.72 vs 6.69 minutes; -29%, P<.001). On a 5-point Likert scale, ratings for the ability to work without stress related to administrative tasks were higher after introduction than before (mean 3.14 vs 2.41; P<.001; median change 0 points, 95% CI 0-1), as were ratings for perceived presence with patients (mean 4.33 vs 3.73; P<.001; median change 0 points, 95% CI 0-1). The median editing time was 93 seconds, and it did not decrease significantly over continued use. Among sustained, fully onboarded adopters in a European health care system, use of an AI medical scribe was associated with reductions in self-reported documentation time, administrative stress, and increase of presence with patients, consistent with findings from prior US-based studies. Because the survey cohort represents a highly selected subgroup of users who adopted and continued using the tool mainly in general practice, these associations may not generalize to clinicians who discontinued use or never fully adopted the scribe, and the generalizability across specialties remains unverified. The single-arm observational design and reliance on retrospective self-report are important considerations when interpreting these associations. A limitation of this analysis is that 138,196 notes were excluded because their recorded editing time was 0; these notes may have been used as generated, used as a starting point and later modified in the medical record system, or discarded, which limits the operational interpretation of the editing-time findings.
Although nonmodifiable medical comorbidities are known to increase postoperative risk following total shoulder arthroplasty (TSA), the impact of potentially modifiable behavioral risk factors is less established. This study evaluated the effects of ischemic heart disease (IHD), type II diabetes mellitus (T2DM), cannabis use disorder (CUD), and nicotine dependence (ND), on short-term postoperative complications following TSA. This retrospective cohort study used the TriNetX US Collaborative Network to identify patients undergoing primary TSA from 2004 to 2024 using CPT codes. Patients were stratified into cohorts according to ICD-10-CM diagnoses of IHD, T2DM, CUD, and ND. Propensity score matching (1:1) was done to balance baseline demographics and BMI. The primary outcome was 90-day complications. Among 59,473 patients included, each comorbidity cohort showed notable increases in complications. Patients with IHD had greater odds of postoperative cardiac arrest (OR 6.825, CI, 3.513 to 13.26), acute kidney failure (OR 3.642, CI, 3.108 to 4.268), and pneumonia (OR 2.892, CI, 2.411 to 3.467). Patients with CUD had the highest odds of acute kidney failure (OR 2.539, CI, 1.556 to 4.143). T2DM was associated with increased skin infections (OR 2.151, CI, 1.806 to 2.562) and cardiac arrest (OR 3.159, CI, 1.692 to 5.898), whereas ND was associated with higher rates of pneumonia (OR 2.081, CI, 1.651 to 2.624) and acute kidney failure (OR 1.893, CI, 1.535 to 2.334). Both nonmodifiable comorbidities and modifiable risk factors markedly increase the risk of specific 90-day postoperative complications following TSA. These findings support targeted preoperative risk stratification and suggest optimizing CUD and ND may improve perioperative outcomes, although prospective studies are needed.
This study aimed to compare the immunogenicity of three meningococcal vaccines used as booster doses in children primed with MPCV-AC in China. A total of 250 eligible children were enrolled to receive MPSV-AC, MPCV-ACYW135, or MPCV-AC as a booster dose. Participants were subdivided into day 7 and day 28 subgroups based on the timing of sample collection. Blood samples were collected at baseline, day 7, and day 28 to measure IgG antibodies against serogroups A and C by ELISA. Baseline GMCs of IgG were 4.34 μg/mL (seropositivity: 79.2%) for serogroup A and 4.36 μg/mL (seropositivity: 82.0%) for serogroup C, both negatively correlated with age and time interval (p < 0.05). All vaccines significantly increased IgG levels at days 7 and 28 post-booster compared with baseline (p < 0.01). In the day 7 group, MPSV-AC yielded a lower GMC (19.14 μg/mL) and seroconversion rate (43.8%) for serogroup A compared with MPCV-ACYW135 (44.69 μg/mL, 78.9%) and MPCV-AC (43.06 μg/mL, 78.1%). In the day 28 group, MPSV-AC showed a comparable GMC for serogroup A (44.42 μg/mL vs. 60.39 μg/mL and 44.66 μg/mL) and a higher GMC for serogroup C (113.40 μg/mL) than MPCV-ACYW135 (59.62 μg/mL) and MPCV-AC (72.75 μg/mL). Only two mild adverse events were reported during the study period. These findings suggest that boosting with MPSV-AC, MPCV-ACYW135, or MPCV-AC is safe and immunogenic; however, further studies are warranted to assess the long-term persistence of immunity conferred by these booster vaccines.
Visit-to-visit blood pressure variability (BPV) may contribute to cerebral white matter lesions (WML) progression, but previous evidence has been inconsistent and limited by methodological heterogeneity. This study aimed to assess the association between BPV and WML progression and its mediating role in the neuroprotective effects of intensive blood pressure (BP) control. This post hoc individual participant data pooled analysis included the MRI substudies of ACCORD MIND and SPRINT MIND. Participants were eligible if they had both baseline and follow-up MRI scans and at least 3 BP measurements from the 3-month visit onward. Systolic BPV was calculated using multiple indices, with variation independent of mean (VIM) prespecified as the primary metric. WML progression was quantified as absolute and annualized changes in abnormal white matter (AWM) volume, with inverse hyperbolic sine (asinh)-transformed total change as the primary metric. Associations between systolic BPV and AWM volume changes were examined using multivariable linear regression, and causal mediation analysis assessed whether systolic BPV mediated the effects of intensive BP control. A total of 952 participants (mean age 64.8 years [SD 7.1]; 400 [42%] women) were included, contributing a median of 12 (interquartile range 10-14) BP measurements. Median AWM volume increased from 1.69 mL to 2.58 mL (0.43 mL per year [SD 0.84]). Higher systolic BPV was independently associated with faster AWM volume progression (β = 0.017, 95% CI 0.001 to 0.033). In raw annualized terms, participants in the highest tertile of SBP-VIM had 0.160 mL/y faster AWM progression than those in the lowest tertile. Intensive BP control was associated with slower AWM volume progression (β = -0.270, 95% CI -0.393 to -0.146). Mediation analysis indicated that systolic BPV partially mediated the association between intensive BP control and reduced AWM volume progression (average causal mediation effect 0.014, 95% CI 0.001-0.034), accounting for 9.15% of the total effect. Higher visit-to-visit systolic BPV was independently associated with faster WML progression. The benefit of intensive BP lowering on white matter integrity was partly mediated by reduced BPV, suggesting BP stability as a modifiable target to prevent white matter injury.
Retrospective study. To clarify the extent to which hip joint mobility increases before and after spinal fusion involving the lumbar spine, and depending on the fused levels. Postoperative changes in hip alignment and mobility in functional positions in patients without obvious organic hip disease remain unclear, particularly with respect to fused levels. This retrospective cohort study included patients who underwent lumbar fusion and had functional lateral radiographs obtained preoperatively and 2 years postoperatively in standing, extension and flexed-seated positions. Lumbar mobility (ΔLL), hip mobility (ΔPFA), and hip-lumbar mobility (defined as the sum of lumbar and hip mobility) were calculated as the change from standing or extension to the flexed-seated position. Patients were categorized by the number of fused levels into the S group (1-4 levels) and the L group (≥5 levels). Longitudinal changes were analysed using a mixed-effects model for repeated measures. The included patients were 100 males and 158 females, with a mean age of 71 years and a mean BMI of 24 kg/m2. In the flexed-seated position, lumbar flexion ability adjusted for pelvic incidence decreased, whereas the pelvic-femoral angle increased after lumbar fusion by a mean of 22° and 8°, respectively, with these changes being more pronounced in the L group. From extension to the flexed-seated position, ΔLL decreased by a mean of 18°, whereas ΔPFA increased compensatorily by a mean of 7° in patients without obvious organic hip disease; however, this increase was insufficient to offset the loss of ΔLL. Lumbar fusion is associated with a postoperative reduction in hip-lumbar mobility despite compensatory increases in hip motion, particularly in patients undergoing long fusion. These findings highlight the importance of evaluating hip mobility before and after lumbar fusion, given its potential implications for adjacent joint loading.
Hypertension is an important risk factor for erectile dysfunction. Yes-associated protein (YAP) is a multifunctional protein involved in diverse biological processes; whether hypertension influences erectile function through the regulation of YAP remains unclear; therefore, this study investigated whether hypertension impairs erectile function in spontaneously hypertensive rats (SHR) by upregulating YAP expression in the penile corpus cavernosum. Twelve 8-week-old male WKY rats were randomly divided into the WKY group and the WKY + LV group (n = 6), and twenty-four 8-week-old male SHR rats were randomly divided into four groups: the SHR group, SHR + NC group, SHR + LV group, and SHR + RES group (n = 6). SHR + RES group received resveratrol (10 mg/kg/d) by gavage for 4 weeks, and the WKY + LV,SHR + LV and SHR + NC groups were treated with a single intracavernosal injection of YAP siRNA lentivirus or empty vector (20 μL/rat, 1 × 109 TU/mL) at week 4. One week later, ICPmax/MAP, serum testosterone, NO, and expression of YAP, Caspase-1, Gasdermin D-N, Caspase-3, and p-eNOS/eNOS in the corpus cavernosum were measured. YAP was predominantly expressed in the cytoplasm and nuclei of endothelial cells in the corpus cavernosum. Compared with the WKY group, the SHR group showed significantly lower NO levels, ICPmax/MAP, and p-eNOS/eNOS expression, but significantly higher expression of YAP, Caspase-1, GSDMD-N, and Caspase-3. In contrast, both the SHR + LV and SHR + RES groups showed significantly increased NO levels and ICPmax/MAP, decreased YAP, Caspase-1, GSDMD-N, and Caspase-3 expression, and reduced endothelial apoptosis and pyroptosis compared with the SHR group (P < .05). Hypertension impairs erectile function by upregulating YAP expression in the penile corpus cavernosum, thereby promoting endothelial apoptosis and pyroptosis and reducing p-eNOS/eNOS and NO production, whereas resveratrol may ameliorate these changes by suppressing YAP expression.