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Background Sudden cardiac death (SCD) is the leading cause of duty‐related death among firefighters. Understanding postmortem cardiovascular abnormalities associated with SCD is critical to guiding fire service cardiovascular disease screening and prevention programs. Methods This study included US firefighters who had a duty‐related death over a 16‐year period (1999–2014) with available postmortem reports (autopsy/medical examiner reports). Cases were systematically reviewed to identify cases of SCD. For each SCD case, the primary etiology of SCD was adjudicated by experts in sports cardiology and cardiovascular pathology. Results Postmortem evaluations were available for 794 of 2100 (37.8%) on‐duty firefighter deaths over the study period (average age, 44±13 years; age range, 17–82 years; 4.0% women). A total of 312 of 794 (39.3%) firefighter deaths were adjudicated as SCD. A total of 255 of 312 (81.8%) SCD events were attributable to coronary artery disease/ischemic heart disease or hypertensive heart disease, which both are associated with traditional cardiovascular risk factors. The leading etiology of SCD among young firefighters (aged <40 years) was also coronary artery disease/ischemic heart disease (24/50 [48.0%]). Of firefighters who had an exertional SCD event thought to be secondary to coronary artery disease (n=97), a total of 62 of 91 (68.1%) had severe fixed coronary stenosis, while 29 of 91 (31.9%) demonstrated acute plaque rupture/thrombosis. Conclusions More than 80% of on‐duty SCD events among US firefighters are due to coronary artery disease and hypertensive heart disease that may be prevented by early disease identification and risk factor modification. Future studies should assess the efficacy of more rigorous firefighter cardiovascular disease screening and management practices.

Background: Hyperkinetic biliary dyskinesia, defined as a gallbladder ejection fraction (EF) ≥80% on cholecystokinin (CCK)-stimulated hepatobiliary iminodiacetic acid scans in the setting of biliary-type pain, has been increasingly recognized as a potential functional gallbladder disorder. The clinical significance of this entity and the role of cholecystectomy remain uncertain. Patients and Methods: We conducted a systematic review and meta-analysis of studies reporting outcomes in patients with CCK-hepatobiliary iminodiacetic acid EF ≥80% who underwent cholecystectomy due to non-acute biliary-type pain. Primary outcomes included mean EF, rates of symptom resolution and improvement following cholecystectomy, and prevalence of chronic cholecystitis on pathology. Secondary outcomes included normal histology rates and symptom reproduction with CCK stimulation. All statistical analyses were conducted in R (version 4.5.0) using a random-effects model to obtain pooled estimates. Results: A total of 14 retrospective studies, including 686 patients, were analyzed. The pooled mean gallbladder EF was 90.27% (95% CI: 88.73–91.80, I 2 = 86.6%). Symptom resolution occurred in 83.1% (95% CI: 76.7–89.4, I 2 = 76.8%), and symptom improvement in 91.6% (95% CI: 89.0–94.2, I 2 = 29.7%) of patients following cholecystectomy. Histopathologic analysis revealed chronic cholecystitis in 85.1% (95% CI: 76.9–93.4, I 2 = 90.6%) of surgical specimens, while normal gallbladder histology was rare, observed in only 9.9% (95% CI: 4.6–15.2, I 2 = 83.7%). The pooled risk ratio indicated a 6.70-fold higher likelihood of chronic cholecystitis compared with normal histology (95% CI: 3.69–12.17, I 2 = 65.2%, P = 0.0022). Functional reproduction of symptoms during CCK stimulation was frequent, with a pooled rate of 78.3% (95% CI: 70.4–86.3, I 2 = 35.6%). Egger regression test suggested potential publication bias for the normal histology outcome ( P = 0.0223), but not for symptom resolution ( P = 0.1589). Conclusions: This meta-analysis suggests that a high gallbladder EF in the setting of biliary-type pain could represent clinically relevant hyperkinetic biliary dyskinesia rather than normal physiology. Cholecystectomy appears to provide meaningful symptom relief in appropriately selected patients, and pathologic findings frequently indicate underlying chronic inflammation. Further studies are needed to establish clear diagnostic cutoffs and guide management.

BACKGROUND: The impact of life-course blood pressure (BP) trajectories on later-life focal left ventricular (LV) fibrosis by late gadolinium enhancement (LGE) remains elusive. METHODS: MyoFit46 prospectively recruited ≈500 participants from a 1946 birth cohort for a cardiovascular magnetic resonance scan at 77 years, assessing LV LGE calculated using the 3-SD method or 5-SD method. Systolic BP (SBP) and diastolic BP were recorded at 36, 43, 53, 63, 69, and 77 years. For each participant, annual rates of BP change (steepness) and area under the BP trajectory (cumulative burden) for each age interval were calculated using mixed-effects models. Associations between life-course BPs and LGE were tested using generalized linear models, adjusted for antihypertensives, demographics, lifestyle, and comorbidities. Time-to-event associations between LGE and incident major adverse cardiovascular event (hospitalizations for coronary artery disease, stroke, heart failure, and atrial/ventricular arrhythmias; n=29) were also evaluated. RESULTS: Among 472 participants (54% male), each 10 mm Hg greater individual SBPs at 36 to 69 years were associated with 6% to 11% greater LV LGE calculated using the 3-SD method (all P ≤0.033), whereas each 10 mm Hg sustained greater SBPs on any age interval from 36 to 69 associated with 16% to 24% greater LGE calculated using the 3-SD method at 77(all P ≤0.005), independent of SBP at 77 years. Each 1 mm Hg/y steeper SBP rise during age intervals 36 to 43, 43 to 53, and 53 to 63 was associated with 6% to 12% greater LGE calculated using the 3-SD method at 77 years. LGE presence was associated with greater major adverse cardiovascular event rates (hazard ratio, 2.5 [95% CI, 1.2–5.2]). CONCLUSIONS: Higher life-course BPs, cumulative burden, and steeper increases were associated with greater older-age LV LGE, which was linked to incident major adverse cardiovascular events. BP trajectories, beyond single-point BP measurements, warrant further investigation as tools to guide BP management strategies.

Klippel-Trénaunay syndrome (KTS) is a rare congenital vascular-overgrowth disorder within the broader spectrum of PIK3CA -related overgrowth syndromes. Although clinical, radiologic, and orthopedic manifestations are well described, the histologic spectrum of KTS-associated pathology remains under-characterized. Clinicopathologic findings from 21 patients with clinically established KTS were reviewed, including 18 with longitudinal clinical follow-up and 3 consultation cases of rare malignant mesenchymal neoplasms. Cases were identified from institutional pathology and clinical databases, and available hematoxylin and eosin-stained sections and ancillary studies were reviewed. The cohort included 11 males and 10 females. Among the 18 clinically followed patients, 12 had limb length discrepancy or asymmetric limb overgrowth, 9 had documented deep vascular malformations, 4 had intra-articular/synovial malformations, and 10 underwent initial orthopedic evaluation or intervention before age 18. Orthopedic morbidity clustered into mechanical overgrowth-related, vascular malformation-related, and soft tissue/wound-related complications. Histologic findings included superficial and/or deep slow-flow vascular malformations, ulceration and granulation tissue, hemosiderin-laden reactive synovium, and destructive hemorrhagic arthropathy. Intra-articular disease recapitulated a hemophilic arthropathy-like pattern, with hemosiderotic synovitis, papillary synovial hyperplasia, and progressive joint destruction with loss of articular cartilage, exposed subchondral bone destruction and remodeling, all attributable to long-standing intra-articular hemorrhage. Three consultation cases showed malignant mesenchymal neoplasia, including 2 angiosarcomas. Recognition of these patterns is important for pathologists evaluating specimens from patients with known or suspected KTS, particularly when findings mimic hemophilic arthropathy, diffuse-type tenosynovial giant cell tumor, nonsyndromic vascular malformation, and/or end-stage destructive arthropathy.

BACKGROUND: Anemia affects more than two billion people worldwide and is common among surgical patients. Despite growing recognition of the risks associated with preoperative anemia, we have limited understanding of the epidemiology of anemia development and recovery. METHODS: This is an observational cohort study of adults undergoing surgery at a large tertiary care medical center from August 2012 to July 2023. Hemoglobin concentrations were obtained preoperatively, during postoperative hospitalization, and through 12 months after surgery. Anemia was defined primarily using World Health Organization criteria (hemoglobin <12 g/dL in women, <13 g/dL in men) and secondarily with a gender-neutral threshold of <13 g/dL. Descriptive analyses summarize preoperative anemia prevalence, postoperative anemia prevalence and incidence, and post-hospitalization anemia recovery across demographic, clinical, and surgical features. RESULTS: 281,217 patients undergoing 423,066 procedures (51.9% among women) were included. Among those with available preoperative hemoglobin assessments (n = 308,959), 28.9% had anemia, with similar prevalence in men (29.5%) and women (28.4%) using World Health Organization (WHO) definitions, but with prevalence increasing to 51.0% in women when using the gender-neutral anemia definition. Preoperative anemia was most common in Black patients (44.0%) and in those ≥75 years (39.6%). Surgical subspecialties showed wide variation in preoperative anemia prevalence, ranging from 18.6% in spine surgery to 45.8% in vascular surgery. Among previously nonanemic patients admitted to the hospital postoperatively, 76.9% developed new postoperative anemia, with the highest incidence in cardiac surgery (97.5%). Women experienced more severe postoperative anemia than men. Overall, 81.1% of patients were anemic at hospital discharge. Recovery was gradual and incomplete: among those discharged with mild, moderate, or severe anemia, 28.5%, 51.9%, and 66.3%, respectively, remained anemic at 12 months. Among patients who were nonanemic preoperatively but developed new postoperative anemia, 29.3% remained anemic at 12 months. CONCLUSIONS: Preoperative and postoperative anemia are highly prevalent, and anemia frequently persists for months after hospitalization. Older adults, women, and Black patients bear a disproportionate burden. Despite this, anemia evaluations and treatments remain underutilized. These findings highlight substantial opportunities for patient blood management (PBM) programs to improve perioperative anemia detection, optimization, and post-discharge management.

Background: The limb symmetry index (LSI) is a measure comparing strength and functional movement between the surgical and nonsurgical limbs, used after anterior cruciate ligament reconstruction (ACLR) to guide rehabilitation and assess return-to-sport readiness. With increasing use of the quadriceps tendon autograft (QT-ACLR), limited data exist on whether the LSI score correlates with patient-reported outcome measures (PROMs). Hypothesis/Purpose: To evaluate the predictive value of postoperative strength and functional LSI tests at 3, 6, and 9 months for short-term PROMs, determine Patient Acceptable Symptom State (PASS) thresholds, and assess differences based on PASS achievement. It was hypothesized that quadriceps strength LSI score would more strongly predict 2-year PROMs than hamstring strength LSI score, and that higher 9-month isokinetic quadriceps LSI scores would be associated with higher International Knee Documentation Committee (IKDC) and Lysholm scores. Study Design: Case series; Level of evidence, 4. Methods: Patients undergoing primary QT-ACLR from 2021 to 2024 with LSI testing during rehabilitation (isometric and isokinetic lower extremity strength, Y-Balance, hop testing) and no revision or additional knee surgery were included. The LSI score was assessed at 3, 6, and 9 months, and PROMs, including Lysholm and IKDC scores, were collected at a mean follow-up of 2.0 ± 0.7 years. Multivariable linear regression was used to evaluate associations between LSI measures and PROMs after adjusting for age, sex, and body mass index (BMI). Receiver operating characteristic analysis was used to determine PASS thresholds. Results: A total of 100 knees in 100 patients (mean age, 25.3 ± 11.2 years; BMI, 25.9 ± 6.5 kg/m 2 ; 52% male) were included. Quadriceps and hamstring strength and functional performance progressively improved from 3 to 9 months, with the LSI score reaching 77% to 81% for quadriceps strength and 98% to 100% for hamstring strength by 9 months postoperatively. At a mean follow-up of 2.0 ± 0.7 years, the mean satisfaction score was 8.4 of 10, the Lysholm score was 90.7, and the IKDC score was 77.8. Linear regression, adjusted for age, sex, and BMI, demonstrated that 3-month isometric quadriceps LSI score had a strong effect on IKDC score, explaining substantial variance (β = 3.9; adjusted R 2 [Adj R 2 ] = 0.36; P < .03); 6-month isokinetic quadriceps and hamstrings showed moderate but significant effects (β = 2.9-3.7; Adj R 2 = 0.13-0.17; P < .05) on IKDC score; and 9-month fast quadriceps had a strong effect explaining substantial variance in Lysholm and IKDC scores (β = 3.9-4.7; Adj R 2 = 0.34-0.35; P ≤ .003). Lysholm and IKDC scores correlated with satisfaction and accurately discriminated PASS thresholds (area under the curve, 0.927-0.937; P < .001). Patients achieving the IKDC PASS demonstrated higher LSI scores across time points and all PROMs. Conclusion: After QT-ACLR, strength-associated LSIs were independently associated with PROMs at a mean 2-year follow-up, after adjusting for age, sex, and BMI. Early isometric quadriceps strength at 3 months predicted higher 2-year IKDC scores, with PASS achievers generally attaining a 60% to 70% LSI score by 3 months. Isokinetic quadriceps strength at 9 months predicted both IKDC and Lysholm scores. These findings highlight the importance of early quadriceps strength recovery and the value of LSI measures in predicting PROMs and informing early rehabilitation.

Objective To characterize regional brain atrophy patterns, evaluate their association with regional leucine‐rich glioma‐inactivated‐1 ( LGI1 ) gene expression, and identify clinical predictors of hippocampal atrophy in LGI1 autoimmune encephalitis (AE). Methods This study compared regional brain volumes in LGI1‐AE patients versus age‐ and sex‐matched healthy controls (HC) and Alzheimer's disease (AD) patients. LGI1 gene expression was derived from the Allen Human Brain Atlas. Multivariable linear regression and generalized linear models were utilized. Results A total of 55 LGI1‐AE patients were included. Median age was 68 years (IQR 62.5–74.2 years) at volumetric analysis, after 19 months (IQR 11–45 months) from symptom onset. Compared with HC ( n = 55) and AD patients ( n = 55), LGI1‐AE patients had greater regional atrophy of the hippocampus, insula, caudate, and putamen ( p < 0.002). Longitudinal analyses demonstrated hippocampal and pallidal atrophy after covariate adjustment. Among those who did not fulfill limbic encephalitis criteria and/or had non‐lesional magnetic resonance imaging, limbic and striatal atrophy were identified compared with HC ( p < 0.01). Regions with the greatest differential atrophy corresponded to higher LGI1 gene expression (Spearman ρ = 0.7, p = 0.005). Severe cognitive deficits at diagnosis ( β = −0.56; p = 0.002) and longer disease duration ( β = −0.01; p = 0.001) independently predicted total hippocampal volume ( R 2 = 0.31). Interpretation LGI1‐AE demonstrates a distinct pattern of limbic and striatal atrophy that differs from AD and aligns with regional LGI1 expression, supporting a model of selective network vulnerability. Greater baseline cognitive impairment and longer disease duration independently associated with hippocampal atrophy, underscoring the potential importance of early diagnosis and treatment to limit structural brain injury. ANN NEUROL 2026

ABSTRACT Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation is a serious complication which may necessitate temporary mechanical support in refractory cases. Here we describe a 63‐year‐old man with end‐stage ischemic cardiomyopathy and severe combined pre‐ and post‐capillary pulmonary hypertension who developed persistent RV failure post‐LVAD. He was intolerant to speed optimization secondary to preload mismatch, and invasive hemodynamics confirmed LV underfilling. An Impella RP Flex was placed for RV support, and biventricular (BiV) pressure‐volume (PV) loops were utilized to ascertain hemodynamic response. With increasing Impella RP Flex support, left ventricular end‐diastolic volume increased with subsequent improvement in left ventricular performance. This case represents the first reported use of BiV PV loop analysis to characterize the physiological effects of Impella RP Flex in a patient with LVAD support, underscoring its utility in understanding device‐ventricular interactions.