Anatomopathological autopsy and postmortem genetic testing play a crucial role in forensic medicine, particularly in elucidating the causes of sudden death (SD) that remain unexplained by conventional methods. This study explores their value in detecting inherited cardiac conditions with medico-legal and preventive implications. From a 15-year forensic cohort, 12 cases of sudden unexpected death in which conventional autopsy was inconclusive or where a hereditary cardiac condition was suspected, were analyzed. Each case underwent histology, toxicology, and targeted next-generation sequencing panels covering genes associated with channelopathies and cardiomyopathies. Variants were classified according to ACMG/AMP guidelines, and family studies were performed when feasible. Integrated pathological and genetic analysis identified pathogenic or likely pathogenic variants in several cases, notably in RYR2 and CALM2 (channelopathies) and FLNC and PPP1R13L (cardiomyopathies). In these cases, genetic findings confirmed the diagnosis, while variants of uncertain significance were detected in others. Postmortem genetic testing proved essential in cases with structurally normal hearts or sub-diagnostic findings, such as concealed arrhythmogenic cardiomyopathy. Familial cascade testing uncovered additional carriers, enabling targeted surveillance and preventive measures. Combining pathological autopsy and postmortem genetic testing significantly improves the diagnostic yield in unexplained SD, uncovers hidden hereditary cardiac conditions, and provides critical information for risk assessment in relatives. Beyond clinical implications, these findings contribute to accurate forensic determinations and prevention of miscarriages of justice. Integrating genetic studies into forensic protocols should become standard practice to ensure both scientific rigor and legal fairness. Not applicable.
OBJECTIVES:Diagnostic delay (DD) is well-documented in SpA, particularly in axial disease. This ancillary analysis from the ASAS-PerSpA study estimated DD across SpA entities, considering the presenting disease manifestation, and evaluated factors associated with DD. METHODS:This study included 4339 patients with any SpA entity (axial (axSpA), peripheral (pSpA), PsA, inflammatory bowel disease-associated SpA (IBD-SpA), ReA and juvenile SpA). DD was assessed using two definitions: (1) the first included extra-musculoskeletal manifestation (EMM) if any, as possible initial symptom, and (2) the second considered strictly the first musculoskeletal manifestation (MM) as the disease onset. DD was statistically compared across disease entities, and associated factors were evaluated using multivariable linear regression models for axSpA, PsA, pSpA and IBD-SpA. RESULTS:The analysis included 2622 axSpA, 1016 PsA, 424 pSpA, 110 IBD-SpA, and 167 other SpA patients. The average DD was shorter using definition 2 (4.5 ± 7.0 vs 6.6 ± 8.6 years). Based on definition 2, DD was longer for axSpA and IBD-SpA (5.6 ± 7.3 and 5.2 ± 7.7 years, respectively), where the first MM was axial, compared with PsA (2.5 ± 6.1 years), pSpA (3.1 ± 5.9 years) and others, where it was peripheral (P < 0.001). Axial first manifestation, younger age at first symptom and older age at study inclusion were associated with longer DD in the four SpA entities. CONCLUSION:DD was longer in axSpA and IBD-SpA compared with PsA, pSpA and other forms of SpA and associated with the phenotype of the presenting symptom. SpA entities and presenting symptoms should be considered when reporting DD in SpA.
143 Background: In ARASENS, darolutamide (DARO) + ADT + docetaxel (DOC) significantly reduced the risk of death by 32.5% (HR 0.68; 95% CI 0.57–0.80; P <0.0001) vs placebo (PBO) + ADT + DOC with similar incidence of treatment-emergent adverse events (TEAEs) between groups in patients (pts) with mHSPC. DARO + ADT + DOC has become one of the standards of care in mHSPC. We report post-hoc efficacy and safety in pts by age subgroups (<75 y, ≥75 y) in ARASENS. Methods: Pts were randomized to receive DARO 600 mg orally twice daily or PBO, with ADT + DOC. Age subgroups were analyzed for baseline characteristics including ongoing comorbidities, treatment duration, completion of DOC therapy, use of first subsequent therapy, key efficacy outcomes, and safety. Results: Of 1305 pts analyzed in ARASENS, ages ranged from 41–89 y, with 1086 pts <75 y (83%; DARO n=546; PBO, n=540) and 219 pts ≥75 y (17%; DARO n=105; PBO n=114). Baseline characteristics were generally similar in the DARO and PBO groups by age subgroup. The most common comorbidities by system organ class in pts <75 y and ≥75 y were vascular (55%, 67%), musculoskeletal/connective tissue (42%, 42%), and metabolism/nutrition (35%, 43%) disorders. Treatment duration was consistently longer with DARO vs PBO (<75 y: 41.2 vs 16.8 mo; ≥75 y: 38.5 vs 15.0 mo). Most patients completed 6 cycles of DOC (<75 y: 89%, 88%; ≥75 y: 80%, 76%). Among pts who entered follow-up, fewer DARO vs PBO pts initiated subsequent therapy independent of age (<75 y: 57% vs 76%; ≥75 y: 54% vs 73%). The overall survival (OS) benefit of DARO vs PBO was consistent across age subgroups (<75 y: HR 0.70, 95% CI 0.58–0.84; ≥75 y: HR 0.61, 95% CI 0.41–0.91). Time to metastatic castration-resistant prostate cancer (mCRPC) was longer with DARO vs PBO across age subgroups (<75 y: HR 0.35, 95% CI 0.30–0.43; ≥75 y: HR 0.42, 95% CI 0.28–0.64) as was time to initiation of subsequent therapy (<75 y: HR 0.40, 95% CI 0.34–0.48; ≥75 y: HR 0.35, 95% CI 0.22–0.54). TEAEs were generally similar between DARO and PBO, with slightly higher incidence rates in older pts. Few patients discontinued DARO or PBO due to TEAEs in both age subgroups (<75 y: 13.2%, 9.1%; ≥75 y: 15.1%, 17.7%). The most common grade 3/4 TEAEs were generally similar between DARO and PBO across age subgroups and occurred most frequently during overlapping DOC treatment. TEAEs commonly associated with androgen receptor pathway inhibitors occurred at similar incidences between treatment groups in both age subgroups. Conclusions: Pts with mHSPC benefited from DARO + ADT + DOC irrespective of age (<75 y and ≥75 y), with consistent improvements in OS, time to mCRPC, and time to initiation of subsequent therapy. DARO was well tolerated in both age subgroups, with similar incidences of TEAEs vs PBO. Clinical trial information: NCT02799602 .
BACKGROUND:Although mechanical thrombectomy (MT) is an effective treatment for large vessel occlusion (LVO) with a high successful recanalization rate, MT failure (MTF) occurs in 10-15% of cases and is associated with unfavorable outcomes. However, little is known about the clinical, technical, and radiological reasons for MTF. We investigated the technical factors associated with MTF. METHODS:We conducted a retrospective analysis of consecutive patients with anterior LVO prospectively included in the ongoing observational multicenter ROSSETTI registry. Patients were categorized according to the success (≥mTICI 2b) or failure (<mTICI 2b) of the MT procedure. Baseline clinical and demographic characteristics, endovascular MT techniques, and angiographic and clinical outcomes were compared. Multivariate analysis for prediction of MTF was performed. RESULTS:We analyzed 4135 patients, including 325 patients (7.9%) with MTF. Patients in the MTF group had a significantly lower Alberta Stroke Program Early CT Score (ASPECTS) at baseline (8 (7-10) vs 9 (8-10)), longer time since last time seen well (279 min vs 262 min), increased MT procedure time (76 min vs 31 min), higher rate of complications (23% vs 4%), higher symptomatic intracerebral hemorrhage (21% vs 7.9%), higher 24 hour National Institutes of Health Stroke Scale score (19 vs 6), worse functional outcome at 3 months (modified Rankin Scale score 0-2, 15.6% vs 53%), and higher mortality (45% vs 20%). Four or more passes were an independent predictor of MTF (OR 3.46, 95% CI 2.58 to 4.63; P<0.001). None of the endovascular techniques demonstrated a higher likelihood of MTF. CONCLUSION:In this study, MTF in anterior circulation LVO was associated with a high complication rate and worse outcomes.
