Transfusion

Background and Objectives: Preterm infants are commonly transfused, yet direct cardiorespiratory effects of red blood cell (RBC) transfusions remain poorly understood. We explored the feasibility of using multicentre electronic health data (EHD) to study such cardiorespiratory responses. Methods: Highly granular routine EHD were collected from preterm infants born <32 weeks gestational age at three European centres. Heart rate, oxygen saturation, and respiratory rate were evaluated 12 hours before and after the RBC transfusion. Results: A total of 321 transfusions in 164 infants were analysed. Overall, there was no significant change in the rate of bradycardia and apnoea following transfusion. Cardiorespiratory parameters varied substantially between infants; e.g. 20% of transfusions were associated with an unexpected, significant increase in heart rate. Respiratory rate and oxygen saturation exhibited similarly heterogenous patterns following transfusion. In sub-group analysis, the proportion of transfusions with increased heart rate was significantly higher within the first two weeks than later (32% vs 13%, p=0.0019). Conclusions: Multicentre EHD extraction allows to identify otherwise masked short-term effects of RBC transfusions on cardiorespiratory parameters, possibly indicating cardiac or pulmonary overload. Such effects may vary with adaptation to anaemia. Analysing EHD may ultimately enable personalized transfusion practice.

Background. Cardiovascular-kidney-metabolic (CKM) syndrome affects nearly 90% of US adults, yet most individuals at early, modifiable stages remain unidentified outside clinical care. Blood donation centers offer a scalable, non-clinical venue for CKM screening, but the potential benefit of screening in this context remains unclear. We projected the population-level impact of effective digital return of results (ROR) to inform the design of a pragmatic trial. Methods. We developed a Monte Carlo simulation (100,000 iterations) of the incident major adverse cardiovascular events (MACE), end-stage renal disease (ESRD), and type 2 diabetes (T2DM) preventable by ROR-prompted, guideline-concordant follow-up among donors in CKM Stages 1-2. The estimand counts only events averted by donors who act because of ROR; the intervention effect was modeled directly on strictly positive support, and action was translated into prevented events through a hazard-based cumulative-incidence difference that counts each donor at most once. We evaluated 18 design cells (donor volumes 300,000, 1 million, and 8 million/year; 5- and 10-year horizons; action-rate gains of +10, +20, and +30 percentage points [pp]) and, in a complementary two-arm simulation, the assurance (expected power) of detecting the effect in a single deployment. Results. Under the primary +20 pp scenario, ROR at a single large blood center (300,000 donors/year) is projected to prevent a median of 2,201 events (95% uncertainty interval [UI], 1,099-4,364) over 10 years, scaling to 58,526 (29,154-116,769) at the national donor pool. All 18 design cells had strictly positive 95% lower bounds. The number needed to screen was 136 and the screening cost $2,045 per event prevented (at $15/donor), both invariant to donor volume. Impact scaled linearly with volume and effect size but sub-linearly with the horizon. Detection of the effect was effectively certain at gains of +20 pp or larger (assurance [&ge;]99.6% in every cell and >99.9% in all but the smallest 5-year cell). Conclusions. Even under the conservative scenario, digital CKM ROR at blood donation centers is projected to prevent hundreds to tens of thousands of incident cardiometabolic events at a screening cost per event well within accepted prevention benchmarks, providing prospective, quantitative justification for a pragmatic, randomized evaluation of digital ROR in non-clinical screening settings.

Introduction Safe and timely blood availability remains a major global health challenge, especially in low- and middle-income countries. Digital tools may accelerate donor contact, but digital reachability alone does not ensure that people will notice, trust and act on urgent requests to support blood donation efforts. We examined factors associated with anticipated engagement in digitally coordinated urgent blood-donor mobilisation among digitally reachable adults in Ghana. Methods We conducted a cross-sectional online survey from September 2025 to January 2026 across Ghana's 16 regions. Participants were recruited via Facebook advertising and snowball sampling. Factors associated with urgent blood-donor mobilisability were assessed under four criteria: high future-donation willingness; high willingness to install a trusted donation app; high willingness to respond to a trusted urgent-request; and high practical flexibility to leave current activities. Descriptive analyses and multivariable logistic regression examined prevalence and associated factors. Results Among 1,067 participants, 577 (54.1%) met all four criteria. Future-donation willingness (91.8%), trusted-app installation willingness (83.2%) and trusted-request response willingness (82.7%) were common, whereas practical flexibility was lower (66.6%). In the adjusted model, high formal health-system trust (adjusted OR (AOR) 3.95, 95% CI 2.08-7.50), high digital-response readiness (AOR 2.26, 1.66-3.08), previous donation (AOR 1.47, 1.08-2.01), high donation knowledge (AOR 1.42, 1.03-1.97) and willingness to donate to strangers were positively associated with high mobilisability. Women (AOR 0.60, 0.43-0.83), participants reporting a work-schedule barrier (AOR 0.43, 0.29-0.66) and those travelling over 30 min to the nearest healthcare facility at night (AOR 0.66, 0.45-0.96) had lower adjusted odds. Conclusions Digital reachability and stated donation willingness may overestimate the population pool available for emergency donation. Digital blood-donor solutions should consider verifiable health-system requests, account for response readiness and current availability, and connect willing individuals with accessible collection options and transport support where needed.

Background: High-sensitivity cardiac troponin (hs-cTn) assays enable safe early discharge of patients at very low risk for myocardial infarction. We previously developed a single-sample rule-out pathway using the ARCHITECT hs-cTnI assay to risk stratify patients with suspected acute coronary syndrome. In a secondary analysis of the POC-ET (Point of Care Evaluation of High-sensitivity Cardiac Troponin) study, we evaluated performance of risk stratification with the Alinity hs-cTnI assay. Methods: Patients presenting with possible myocardial infarction in the POC-ET (NCT05665127) study were included. The primary outcome was type 1, 4b or 4c myocardial infarction or cardiac death at 30 days. Cardiac troponin I (cTnI) was measured in stored materials using the ARCHITECT and Alinity hs-cTnI assays. The sex-specific 99th percentile upper reference limit (URL) are 34 ng/L in men and 16 ng/L in women for both assays. Agreement was assessed with Bland-and-Altman limit of agreement method, Passing Bablok regression, and Pearson's correlation coefficient. Distributions of presentation measurements were compared with Kolmogorov-Smirnov test. Performance was evaluated in the overall population and prespecified subgroups. The negative predictive value (NPV) and sensitivity were determined and proportion of patients identified as low, intermediate, and high risk were calculated and modelled using ordinal logistic regression. Results: In 986 patients (60 [51-70] years, 38% female), 78 (7.9%) had a primary outcome. Strong agreement was found in the raw cTnI measurements (99% samples within the Bland-Altman limit of agreement; correlation coefficient r: 0.967 (95% CI 0.964-0.969, P<0.001); Passing Bablok regression: slope 1.12 [1.11-1.13], intercept -0.16 [-0.18 to -0.13]). At presentation, distributions of cTnI measurements by the two assays were similar (P=0.810). Both assays showed comparable diagnostic performance using a risk stratification threshold of <5 ng/L and the sex-specific diagnostic threshold, with the same NPV (Alinity 100 [99.7-100]% versus ARCHITECT 100 [99.7-100]%) and sensitivity (Alinity 100 [97.3-100]% versus ARCHITECT 100 [97.3-100]%). Similar proportions of patients stratified as low- (Alinity 67% versus ARCHITECT 67%), intermediate-risk (23% versus 24%) and high-risk (10% versus 9%) at presentation with minor reclassification. Similar efficacy was observed across subgroups stratified by sex, age, history of myocardial infarction, renal function, and symptom duration. Conclusions: The Alinity hs-cTnI and the ARCHITECT hs-cTnI assays can be used interchangeably in the assessment of suspected myocardial infarction with comparable safety and efficacy.

Background VEXAS syndrome is a late onset autoinflammatory disease caused by somatic UBA1 mutations and characterized by heterogeneous systemic and hematologic manifestations. We aimed to describe all identified Belgian cases through a national multicenter cohort. Methods We conducted a retrospective study across four Belgian tertiary centers. Clinical, biological, genetic, therapeutic, and outcome data were collected using standardized anonymized case report forms. Analyses were descriptive. Results Twenty-one male patients were identified between January 2018 and May 2025. General symptoms such as Fatigue, weight loss and sweating occurred in 95% of cases. The most frequent manifestations were cutaneous (85.7%), hematologic (76.2%), articular (66.7%), thromboembolic (57.1%), chondritis (42.9%), ophthalmologic (38.1%), pulmonary (38.1%). Other manifestations also included vasculitis (61.9%). At diagnosis, 95% had anemia, macrocytic in 57%, and 28.6% had thrombocytopenia. Corticosteroids were the main first line therapy. Second line treatments included anti IL 6 agents (46.7%), JAK inhibitors (20%), and azacitidine (14.3%). Complete remission occurred in 50% of patients receiving anti IL 6 therapy and in 33% treated with either JAK inhibitors or azacitidine. Two patients underwent allogeneic stem cell transplantation, one died from infectious complications. Twenty six infectious episodes were recorded, including opportunistic infections. Six patients (28.6%) died during follow-up, four from infectious complications. Conclusion This first Belgian national cohort confirms the clinical heterogeneity of VEXAS syndrome and highlights substantial infectious morbidity and mortality. Access to targeted second-line therapies, particularly anti IL-6 agents and JAK inhibitors, remains challenging despite apparent clinical benefit.

Background: Percutaneous mechanical circulatory support (pMCS) is increasingly used in critically ill patients, yet its value in relation to cost and outcomes remains unclear. We evaluated national variation in utilization, outcomes, and cost, and introduced a value of care framework integrating risk-adjusted outcomes and expenditures. Methods: We performed a retrospective cohort study using the National Inpatient Sample to identify non-elective hospitalizations of critically ill patients undergoing intra-aortic balloon pump (IABP) or percutaneous left ventricular assist device (pLVAD) placement using ICD-10 codes. Multivariable logistic regression and generalized linear models were used to estimate expected outcomes and costs. Observed-to-expected (O/E) ratios were calculated, and a value index was derived to compare procedural strategies. Results: A total of 57,910 weighted hospitalizations were included (IABP 78%, pLVAD 22%). In-hospital mortality exceeded 30% across regions. Significant regional variation was observed, with the West demonstrating the highest costs and the Midwest the lowest (p<0.001). Mean hospital charges were higher for pLVAD compared with IABP ($403,731 vs $320,769). Both strategies achieved outcomes better than expected after risk adjustment (O/E 0.92); however, costs were higher than expected for both, with greater relative cost inflation observed for IABP (O/E 1.41) and higher absolute costs for pLVAD. In value-of-care analysis, IABP was associated with lower cost and comparable outcomes, while pLVAD demonstrated higher cost without proportional outcome improvement. Conclusion: Substantial variation exists in the cost, outcomes, and value of pMCS strategies. While both IABP and pLVAD achieve favorable risk-adjusted outcomes, pLVAD is associated with higher costs without commensurate clinical benefit.

Background: Primary malignant cardiac tumors (PMCTs) are rare and histologically heterogeneous. Objective: To compare demographics, specific ICD-O-3 morphologies, first-course treatment patterns, annual registered case counts, and unadjusted overall survival between soft-tissue and hematologic PMCTs. Methods: We identified 730 PMCT cases diagnosed from 2000 to 2021 in SEER 18 (ICD-O-3 topography C38.0). Histologic lineage was assigned from ICD-O-3 morphology. Comparative analyses included soft-tissue (n=458) and hematologic (n=212) tumors. First-course variables were primary-site surgery, chemotherapy (yes versus no/unknown), and radiotherapy (radiation versus none/unknown). Groups were compared with chi-square tests. Overall survival was estimated with Kaplan-Meier methods; follow-up was truncated at 120 months. Results: Soft-tissue PMCTs occurred predominantly at ages 45-64 years (67.9%), whereas hematologic PMCTs occurred predominantly at age [&ge;]65 years (63.2%; p<0.001). Men comprised 59.9% of hematologic and 49.3% of soft-tissue cases (p=0.014). The leading soft-tissue morphology was hemangiosarcoma/angiosarcoma (ICD-O-3 9120/3; 201/458, 43.9%); synovial sarcoma accounted for 20/458 cases (4.4%). Diffuse large B-cell lymphoma, NOS, accounted for 131/212 hematologic tumors (61.8%). Any primary-site surgery was recorded in 66.6% of soft-tissue versus 15.6% of hematologic cases (p<0.001). Chemotherapy was recorded in 67.5% versus 51.1% (p<0.001), and radiotherapy in 9.0% versus 20.5% (p<0.001). In exploratory Kaplan-Meier analyses, hematologic patients with recorded chemotherapy had higher unadjusted 120-month overall survival than those without recorded chemotherapy (42.0% versus 12.2%; log-rank p=7.5x10-). Radiation-associated survival differences were not statistically significant in either lineage. Conclusions: Soft-tissue and hematologic PMCTs have distinct age distributions, named histologies, and first-course treatment patterns in SEER. These findings describe registry coding and do not establish treatment effectiveness or population incidence.

Background: Sickle cell anaemia (SCA) is characterised by chronic haemolysis, inflammation, platelet activation, and recurrent vaso-occlusive complications. Mean platelet volume (MPV) is a readily available platelet index, but evidence regarding its relationship with disease severity in paediatric SCA remains limited and inconsistent, particularly in African populations. Objective: To evaluate the relationship between MPV and disease severity among children with SCA in Kwara State, North-Central Nigeria. Methods: This hospital-based cross-sectional study included 51 clinically stable children with confirmed SCA consecutively recruited from the paediatric haematology clinic of Children Emergency Specialist Hospital, Ilorin. Complete blood count, including MPV, was performed using a Rayto RT-7600 automated haematology analyser. Disease severity was assessed using a composite clinical and laboratory scoring system based on a previously described method. Pearson's correlation, Spearman's rank correlation, simple linear regression, and the Kruskal-Wallis test were used as appropriate. Statistical significance was set at p < 0.05. Results: Of 51 participants, 14 (27.5%) had mild, 33 (64.7%) moderate, and 4 (7.8%) severe disease. Mean MPV was 9.34 +/- 0.76 fL (range, 8.0-11.2). Pearson's correlation showed a weak positive, non-significant linear relationship with severity score (r = 0.231, p = 0.103), whereas Spearman's analysis showed a weak positive monotonic association (rho = 0.286, p = 0.042). Regression explained 5.3% of severity-score variation (R2 = 0.053, p = 0.103). MPV did not differ significantly across severity categories (H = 2.163, p = 0.339). MPV correlated inversely with haemoglobin (r = -0.556, p < 0.001) and positively with platelet count (r = 0.307, p = 0.029). Conclusion: MPV showed a weak relationship with disease severity but inconsistent statistical evidence across analyses. The limited explained variance and absence of significant differences between severity categories do not support MPV as a standalone severity marker. Larger longitudinal studies are warranted. Keywords: Sickle cell anaemia; Mean platelet volume; Disease severity; Platelet indices; Paediatric haematology; Cross-sectional study; Nigeria.

Background: Sleeve gastrectomy is the most frequently performed bariatric procedure worldwide but is associated with the development of de novo gastroesophageal reflux disease (GERD). Hiatal hernia has been identified as a relevant anatomical factor in postoperative reflux, although most studies evaluate it dichotomously without analyzing whether its size influences GERD risk. The aim was to evaluate the association between preoperative hiatal hernia size and de novo GERD after sleeve gastrectomy. Methods: Retrospective, single - center, observational study of patients undergoing sleeve gastrectomy at Hospital Central Norte de Petroleos Mexicanos (2018 - 2025). Demographic and clinical characteristics, endoscopic classification of hiatal hernia size (small <2 cm, medium 2.1 - 4 cm, large >4 cm), and evidence of de novo GERD were analyzed using descriptive statistics, Fisher's exact test, odds ratio (=R) estimation with 95% confidence intervals (CI), and binary logistic regression. Statistical significance was set at p<0.05. Results: Fiftysix patients were included (mean age 48.3 {+/-} 8.1 years; 67.9% male). Hiatal hernia classification was conclusive in 46 patients (82.1%): 63.0% no hernia, 4.3% small, 30.4% medium, and 2.2% large. De novo GERD occurred in 14.0% of patients without preexisting GERD (6/43). No significant association was found between hiatal hernia size and de novo GERD (Fisher p=0.515). In the reduced logistic model, neither hiatal hernia (medium/large vs. absent/small; OR 3.47; 95% CI 0.50 - 29.43; p=0.207) nor age (OR 1.02; 95% CI 0.90 - 1.13; p=0.754) was significantly associated. No evaluated factor (sex, smoking, alcohol, age) reached significance. Conclusions: In this cohort, no statistically significant association was demonstrated between preoperative hiatal hernia size and de novo GERD after sleeve gastrectomy; however, the low number of events limits the ability to exclude a clinically relevant association. These findings are compatible with a multifactorial mechanism rather than with the isolated presence of this finding. Prospective studies with larger sample sizes and standardized reflux assessment instruments are required to confirm these results.

Background: The relative merits of infrainguinal bypass and primary major lower limb amputation (MLLA) for chronic limb-threatening ischaemia (CLTI) remain uncertain, and the baseline profiles of patients selected for each strategy are poorly described. Methods: A systematic review and meta-analysis were undertaken in accordance with PRISMA 2020 and prospectively registered (PROSPERO: CRD42022356094). MEDLINE, Embase, CENTRAL, and CINAHL were searched from inception to March 2025. Prospective studies of adults with CLTI undergoing primary infrainguinal bypass or primary MLLA were eligible. Mortality, major adverse cardiovascular events (MACE) and subsequent amputation outcomes were synthesised using random-effects meta-analysis of proportions. Baseline comorbidity profiles were also extracted. Results: Twenty-seven studies involving 6,576 patients were included: 5,779 underwent infrainguinal bypass and 797 underwent MLLA. After bypass, pooled mortality was 3.7% at 30 days (95% CI 2.8%-4.9%, I2 = 49.4%), 18.5% at 1 year (95% CI 15.6%-21.9%, I2 = 62.3%), and 54.3% at 5 years (95% CI 50.5%-58.0%, I2 = 0%). After MLLA, pooled mortality was 9.2% at 30 days (95% CI 4.1%-19.3%, I2 = 73.5%), 28.5% at 1 year (95% CI 13.3%-51.0, I2 = 70.8%), and 39.9% at 2 years (95% CI 0.3%-99.3, I2 = 90.5%), although longer-term estimates were limited by sparse data and marked heterogeneity. Thirty-day MACE was 6.5% (95% CI 4.3%-9.7, I2 = 63.5%) after bypass and 2.8% after MLLA (95% CI 0.1%-37.6%, I2 = 0%). Early subsequent major amputation after bypass occurred in 3.9% of patients (95% CI 2.0%-7.7%, I2 = 91.2%), rising to 16.2% at 1 year (95% CI 12.6%-20.5%, I2 = 82.0%) and 33.3% at 3 years (95% CI 20.1%-49.8%, I2 = 0%). Early re-amputation after MLLA occurred in 10.9% of patients (95% CI 4.5%-24.4%, I2 = 40.3%). Baseline comorbidity burden was high in both groups, with substantial heterogeneity across studies. Conclusions: CLTI carries a poor prognosis regardless of treatment strategy. Infrainguinal bypass is associated with lower early mortality and better early limb preservation than primary MLLA, but long-term survival remains poor and later limb failure is common. Primary MLLA is not a low-risk alternative. Better contemporary comparative evidence utilising modern causal inference approaches is needed to support individualised decision-making.

Background: Adult congenital heart disease (ACHD) patients are prone to HLA-antibody formation from multiple surgeries, transfusions, and prosthetic surgical material. Females with ACHD may accrue additional, non-surgical alloantigen exposure. Whether sex modifies the impact of allosensitization on heart transplant (HT) access and outcomes in ACHD remains unknown. Methods: We retrospectively analyzed the OPTN/UNOS registry of adults with ACHD listed for first-time HT (2018-2025). Sensitization was defined by calculated panel reactive antibodies (cPRA) at listing. We tested the sex x sensitization (highly sensitized, cPRA >50%) interaction on transplant access using Fine-Gray competing-risks regression, treating transplantation as the event of interest and death or removal from the waitlist as competing events, and on post-transplant survival using multivariable Cox proportional-hazards regression, both adjusted for age at listing, mechanical support at listing, and the number of distinct prior cardiac surgery categories. Results: Among 856 candidates (38% female), females were more often highly sensitized than males (23% vs 14%; age-adjusted OR 1.81, 95% CI 1.26-2.61), even after adjusting for surgical burden. Sensitization reduced transplant access in females (84% to 71%; median wait 60 to 110 days, p < 0.001) but not males (79% vs 79%, median wait 88 vs 98 days). In adjusted Fine-Gray models, the subdistribution hazard for transplant was reduced in sensitized females (sHR 0.54, 95% CI 0.41-0.72) with no effect in males (sHR 0.96, 95% CI 0.73-1.26), and the sex x sensitization interaction was significant (interaction sHR 0.64, 95% CI 0.44-0.94, p = 0.02). Post-transplant mortality was numerically higher in sensitized than non-sensitized candidates in both sexes and the sex x sensitization interaction on 1-year mortality was not significant. The sex-asymmetric effect persisted and was more pronounced in the multiorgan candidates. Conclusions: Allosensitization is not a sex-neutral barrier to transplant in HT candidates with ACHD. Females are more sensitized and have reduced transplant access without differences in 1-year mortality. The female excess in sensitization is not accounted for by surgical burden, and the exposures responsible remain to be defined. These findings warrant a sex-aware listing strategy and further studies.

Background: Bailout cardiac surgery during transcatheter aortic valve replacement (TAVR) is uncommon but remains associated with substantial morbidity and mortality. Although registries have described its incidence and major causes, they often provide limited detail regarding device-related failure mechanisms, attempted transcatheter rescue, and the clinical pathway leading to surgical conversion. We aimed at analyzing post-marketing safety reports from the U.S. Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database to characterize the mechanisms, management strategies, and reported outcomes of bailout surgery during or shortly after TAVR. Methods: We retrospectively analyzed FDA MAUDE reports received from July 1, 2016, through June 30, 2026. Eligible reports described unplanned urgent or emergent open cardiac surgery during or immediately after TAVR. Candidate reports were screened, adjudicated, and deduplicated at the clinical-event level. Events were classified by precipitating complication, transcatheter rescue, operative pathway, and reported outcome. Associations were evaluated using permutation tests, Fisher exact tests with Benjamini?Hochberg correction, adjusted regression models, and sensitivity analyses. Results: After screening 43,239 initial reports, we identified 376 bailout-surgery events, with survival status was documented in 254, including 104 deaths and 150 survivors, corresponding to 40.9% reported mortality. Valve embolization, migration, or malposition was the most frequent complication phenotype (32.4%), whereas ventricular perforation or laceration was associated with the highest mortality (74.1%; OR, 4.86; 95% CI, 1.97?11.99). Mortality differed across complication phenotypes (p<0.001) and operative pathways (p<0.001), but not across transcatheter rescue pathways (p=0.355). Valve explantation with SAVR was associated with lower reported mortality (18.9%; OR, 0.29; 95% CI, 0.12?0.69), whereas unspecified surgery or access/support alone was associated with higher mortality (56.9%; OR, 3.04; 95% CI, 1.80?5.12). Ancillary analyses identified potential platform-specific differences in complication and management patterns, while bailout timing was not independently associated with mortality after adjustment. Conclusions: In this MAUDE analysis, bailout cardiac surgery after TAVR was most commonly precipitated by valve embolization, migration, or malposition, whereas ventricular perforation or laceration was associated with the highest reported mortality. Outcomes differed across complication and operative pathways but not across transcatheter rescue strategies or bailout timing after adjustment. These findings identify clinically relevant post-marketing safety signals but should not be interpreted as incidence estimates, comparative device risks, or causal treatment effects.

Background and Objectives: Recurrence following burr-hole drainage of chronic subdural haematoma (cSDH) occurs in 10-25% of cases, sustained by neovascularisation of the subdural neomembrane supplied by the middle meningeal artery (MMA). MMA embolisation reduces recurrence; whether incidental burr-hole intersection of MMA branches during drainage confers similar benefit is unknown. Methods: We performed a multicentre retrospective cohort study of consecutive adults undergoing burr-hole drainage for cSDH at two UK tertiary neurosurgical centres. Postoperative thin-slice CT was used to classify burr-hole intersection of the underlying MMA groove (no hit, distal-branch hit or main-branch hit) and measure perpendicular burr-hole-to-MMA-groove distance. Co-primary outcomes were radiological recurrence and recurrence requiring intervention. Patient-clustered multivariable logistic regression adjusted for prespecified clinical covariates and treating site. Results: 227 patients (284 operated hemispheres) were included. Radiological recurrence decreased from 34.4% with no branch hit to 22.9% with main-branch intersection, with the gradient confined predominantly to unilateral cSDH. Main-branch intersection was associated with lower adjusted odds of radiological recurrence in unilateral cSDH (adjusted OR 0.30, 95% CI 0.11- 0.81; P = .018), with a similar but non-significant association in the overall cohort (adjusted OR 0.53, 95% CI 0.26-1.07; P = .075). Burr-hole-to-MMA-groove distance demonstrated a more consistent association: in the overall cohort, each 5-mm increase independently increased the odds of radiological recurrence (adjusted OR 1.38, 95% CI 1.04-1.82; P = .025). In unilateral cSDH, each 5-mm increase was independently associated with both radiological recurrence (adjusted OR 1.45, 95% CI 1.03-2.04; P = .034) and recurrence requiring intervention (adjusted OR 1.52, 95% CI 1.05-2.20; P = .027). Conclusion: Main-branch intersection of the middle meningeal artery during routine burr-hole surgery is associated with lower recurrence of unilateral cSDH, while the accompanying burr-hole-to-MMA-groove distance gradient provides biologically plausible support for a dose-response relationship. Together, these findings provide mechanistic rationale for prospective evaluation of intentional neuronavigation-guided MMA targeting (BURR-MMA; NCT07549893).

Background. Durable mitral isthmus (MI) block remains challenging in persistent atrial fibrillation (PeAF) ablation. Recent epicardial vein of Marshall (VoM) recordings have shown incomplete MI transmurality and time-dependent conduction recovery after pulsed field ablation (PFA). Whether systematic VoM ethanol infusion (VoM-EI) followed by focal PFA provides stable acute MI block remains unknown. **Objectives.** To assess the incidence, timing, and procedural implications of early MI conduction recovery after systematic VoM-EI followed by focal Sphere-9 PFA. Methods.In this prospective single-center study, 55 consecutive patients undergoing first ablation for symptomatic PeAF with planned MI ablation were screened. VoM-EI was systematically attempted before left atrial access and successfully performed in 51 (92.7%), who constituted the study cohort. Pulmonary vein isolation, roof-line, and MI ablation were performed with the Sphere-9? lattice-tip catheter. After bidirectional MI block, conduction was systematically reassessed during a standardized 30-minute waiting period. Results.Mean age was 70.3 {+/-} 8.2 years, and 36 patients (70.6%) were men. Initial bidirectional MI block was achieved in 50/51 patients (98.0%). During the waiting period, conduction recovered in 9/50 (18.0%; 95% CI, 9.8%-30.8%), at a median of 16 minutes (IQR, 10-20; range, 8?23). Six of 9 patients with recovery (66.7%) required targeted coronary sinus (CS) ablation. Block was restored in all 9, yielding a final block rate of 50/51 (98.0%). Median procedure duration was 82 minutes (IQR, 73-95), with no major complications. Conclusions. Immediate bidirectional MI block was not synonymous with stable block. Despite systematic VoM-EI followed by focal Sphere-9 PFA, conduction recovered in approximately one in five patients, including beyond 20 minutes, and two thirds required targeted CS ablation. These findings support standardized 30-minute reassessment and targeted CS interrogation rather than reliance on immediate block. Chronic invasive remapping is required to determine whether this strategy improves long-term MI block durability.

Objective: Whether a scheduled antiseizure medication (ASM) continues on schedule across the ICU-to-floor transfer has not been characterized. We quantified ASM administration-gap frequency across this transfer and compared it with gap frequency during matched non-transfer intervals in the same patient and drug. Methods: In this retrospective MIMIC-IV (version 3.1) cohort study, we identified epilepsy and status-epilepticus admissions with an ICU stay followed by floor transfer and a scheduled ASM order active at ICU departure. A gap was defined as an interval exceeding 1.5 times the expected dosing interval between the last ICU dose and first floor dose, or no further dose before discharge, and compared with a matched non-transfer control interval in the same patient and drug (paired McNemar test). A multivariable model evaluated six prespecified clinical predictors; sociodemographic variables were summarized descriptively. Results: Among 2,469 ASM transition-by-drug observations (1,583 admissions, 1,335 patients), an administration gap occurred in 251 (10.2%; 95% CI, 8.7%-11.7%). Gap frequency across the transfer exceeded frequency during matched non-transfer control intervals in the same patient and drug: a paired rate difference of 5.8 percentage points (95% CI, 4.4-7.1; 7.5% vs 1.7%; P = 7.3 x 10^-22) before the transfer and 6.4 percentage points (95% CI, 4.9-7.9; 8.9% vs 2.5%; P = 1.9 x 10^-23) after. Gap rates were similar for intravenous-available (9.9%) and oral-only (11.4%) drugs (rate difference, 1.5 percentage points; 95% CI, -1.6 to 4.5; P = .34). None of six prespecified predictors reached significance after correction. Significance: An antiseizure medication administration gap occurred in approximately 1 of every 10 drug-transition observations at the ICU-to-floor transfer, exceeding matched non-transfer gap rates by 5.8 to 6.4 percentage points. This transfer-associated excess, rather than any single medication or patient characteristic, supports a structured medication-continuity check.

Objective: To determine whether paradoxical relief, feeling unusually better after a seizure compared to before it, is more common after functional/dissociative seizures (FDS) than epileptic seizures (ES), quantify its diagnostic accuracy, and explore its relationship with preictal symptoms. Methods: Consecutive patients admitted to a tertiary epilepsy unit for prolonged inpatient EEG monitoring underwent a structured clinical interview on admission, before final multidisciplinary diagnostic classification. Preictal dissociative and autonomic/somatic symptom burden was assessed using items adapted from established questionnaires. Diagnostic classification incorporated clinical history, seizure semiology, video electroencephalography findings, and collateral information. Patients with dual or indeterminate diagnoses were excluded. Associations with paradoxical relief were examined using logistic regression, followed by an exploratory mediation analysis. Results: Of 176 patients assessed, 66 with FDS and 65 with ES were included. Paradoxical relief was reported by 46/66 patients with FDS (69.7%) and 10/65 with ES (15.4%; unadjusted odds ratio [OR] 12.65, 95% confidence interval [CI] 5.57 to 31.09). As a diagnostic signal for FDS, paradoxical relief had 69.7% sensitivity (95% CI 57.1 to 80.4), 84.6% specificity (95% CI 73.5 to 92.4), a positive likelihood ratio of 4.53 (2.51 to 8.19), and a negative likelihood ratio of 0.36 (0.24 to 0.52). FDS diagnosis remained independently associated with paradoxical relief after adjustment (OR 10.59, 95% CI 3.42 to 38.06). In a parallel mediation analysis, dissociative symptom burden showed a significant indirect effect, accounting for 19.5% of the association between diagnostic group and relief, whereas the indirect effect through somatic/autonomic symptom burden was not significant. Significance: Paradoxical relief is substantially more common after FDS than ES and may provide a simple, clinically useful diagnostic signal. Its absence does not exclude FDS, and the finding requires external validation. The association with dissociative symptoms is exploratory and supports prospective investigation of whether relief reflects transient resolution of a disturbed, disembodied preictal state.

Background: Fluctuations in pain intensity are intrinsic to non-specific chronic low back pain (nsCLBP). Nevertheless, pain fluctuations have rarely been considered when investigating pathophysiological mechanisms. Therefore, a novel study protocol was developed and implemented to systematically assess the impact of fluctuating pain states on pain-related measures. Methods: The final study cohort consisted of 45 nsCLBP patients and 47 age- and sex-matched healthy controls (HCs). Patients participated in three visits, conducted during different pain states (i.e. clinically relevant pain, low-intensity clinical pain / pain-free, clinically irrelevant pain induced using a Qutenza 8% capsaicin patch). Pain fluctuations were monitored through online assessments every four days and guided the pseudorandomized visit scheduling. HCs participated in a single visit. Each study visit comprised a multimodal battery of pain-related measures. Results: 93.33% of patients completed all three visit types in a pseudorandomized order (chi-squared=1.50, p=0.826). Visit scheduling was possible due to the high self-report adherence (median=93.48%), unrelated to self-report burden (rho=-0.097, p=0.53). Study visits were conducted during different pain states, as indicated by: i) the significantly higher low back pain intensity in the clinically relevant pain visit (mean[SD]: 3.98[0.90]), compared to the low-intensity clinical pain (1.03[0.86]) and clinically irrelevant pain (1.13[0.82]) visits (p-values<0.001), as well as by ii) the successful induction of a moderate-to-high clinically irrelevant pain across assessments. Conclusion: Despite scheduling complexity and pain state transition uncertainty, a pain state-dependent pseudorandomized study design is feasible and could improve the understanding of nsCLBP mechanisms.

Background: Fibrosis, characterised by excessive accumulation of collagen type I (COL1), is a common feature of chronic diseases, including liver diseases (LDs), chronic kidney disease (CKD) and heart failure (HF). COL1 degradation products can be detected in urine by proteomics/ peptidomics analyses and may serve as non-invasive biomarkers of fibrosis. We aimed to identify a common molecular signature of fibrosis across these diseases that may ultimately guide interventions to slow disease progression and prevent organ damage. Methods: Using capillary electrophoresis coupled to mass spectrometry (CE-MS), naturally occurring COL1 degradation products (peptides) in the urine of patients with fibrotic disease, LDs (n=127), CKD (n=263) or HF (n=187), were investigated and compared with the same number of matched controls. Disease-associated COL1 peptides were identified separately for each condition, and peptides showing consistent associations across the three diseases were selected to define a common fibrosis signature. A support vector machine model based on the selected peptides was developed and validated in independent cohorts of patients with LDs (n=110), CKD (n=93), HF (n=32) and controls (n=643). Results: We identified a common fibrotic signature consisting of 50 COL1 degradation products, mainly downregulated in fibrosis. A model based on these peptides achieved a strong performance, with an area under the receiver operating characteristic curve (AUC) of 0.935 (95% confidence interval (CI) 0.917-0.953, p<0.0001) in an external validation cohort comprising pooled disease groups (LDs, CKD, and HF) and controls. Performance was maintained in LDs, CKD and HF, with AUCs of 0.917 (95% CI 0.890-0.944, p<0.0001), 0.951 (95% CI 0.931-0.971, p<0.0001) and 0.950 (95% CI 0.903-0.997, p<0.0001), respectively. The model scores were significantly associated with fibrosis stage in LDs (p=0.0097) and with interstitial fibrosis and tubular atrophy in CKD (p=0.045). Conclusion: A model of urinary COL1 peptides captures a shared collagen degradation signature across organs and diseases, enabling the non-invasive assessment of fibrosis irrespective of its origin. As these peptides exclusively reflect collagen degradation, the findings suggest impaired collagen degradation as a driver in fibrosis. Future clinical studies are warranted to evaluate the utility of this model for early fibrosis detection and earlier implementation of anti-fibrotic interventions.

Background: Higher Body Mass Index (BMI) is an established risk factor of sleep disturbance. It is not known if the effect is homogeneous across the lifecourse or if there is a particular time point in life that might be best to target. Methods: Two-sample Mendelian randomization (MR) was used to investigated the effect of childhood adiposity (adjusting on adulthood adiposity and obstructive sleep apnea (OSA)) on insomnia, morning chronotype, sleep duration, daytime sleepiness and daytime napping. Similarly, total, and direct effect of adulthood adiposity on these outcomes was explored. We used summary statistics from a genome-wide association study (GWAS) of UK Biobank for childhood and adulthood adiposity (n=453,169) and large-scale consortia of OSA (Million Veteran Program) (n=410,268), insomnia, and chronotype (23andMe) (n=1,978,022 and n=248,1000, respectively). Results: Two-sample univariable MR analysis provided no evidence of an effect of genetically predicted childhood adiposity on later life insomnia (Odds ratio (OR)= 0.94, 95% Confidence interval (CI)= 0.87, 1.03). Whereas, multivariable MR (adjusted for adulthood adiposity) analysis provide strong evidence of direct protective effect of genetically predicted childhood adiposity on later life insomnia (OR= 0.70, CI= 0.64, 0.77). Further, both in univariable and multivariable MR, a strong positive effect of increased childhood body size on morning chronotype was observed (OR= 1.16, CI= 1.01, 1.33 and OR= 1.36, CI= 1.15, 1.62, respectively) after accounting for adulthood body size. In both analysis the estimate did not change considerably after aditionally adjusting for OSA. However, childhood and adulthood adiposity found to be associated with OSA and OSA with insomnia. In both univariable and multivariable analysis, increased body size in adulthood increased the risk of having insomnia and a morning chronotype. Conclusions: The findings suggest that higher body size in childhood is not a risk factor for later life insomnia, whereas higher body size in adulthood was. Further, if healthy body size is maintained in adulthood, high childhood adiposity may decrease the risk of insomnia and increase the risk of being a morning person in later life. Keywords: childhood, adulthood, obesity, insomnia, morning chronotype, medelian randomization

To evaluate the cost-utility and 5-year budget impact of first-line olaparib plus abiraterone versus abiraterone alone for metastatic castration-resistant prostate cancer (mCRPC) in China after the eleventh round of volume-based procurement (VBP). The intention-to-treat (ITT) population was assigned primary decision-analytic weight; the prespecified BRCA1/2-mutated (BRCAm) subgroup was a supporting analysis.