Mental health disorders are linked with increased cardiovascular disease and mortality risk, yet national trends in cardiovascular mortality among US adults with mental health disorders remain incompletely characterized. We performed a nationwide multiple cause of death analysis using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death database to evaluate long-term trends and demographic patterns in cardiovascular mortality among US adults aged 25 years or older with mental health disorders between 1999 and 2024. Adults with mental health disorders were identified using International Classification of Diseases, Tenth Revision codes F00-F99, and cardiovascular deaths were reported using circulatory system codes (I00-I99). Age-adjusted mortality rates and crude mortality rates were calculated, and Joinpoint regression was used to derive annual percentage change and average annual percent change (AAPC). Between 1999 and 2024, more than 7.2 million cardiovascular deaths occurred among US adults with mental health disorders. Cardiovascular mortality rose steadily through the study period, and across sex, race/ethnicity, age group, geographic region, and urbanization levels. The greatest increases were noted among adults ages 55-64 years (AAPC: 6.90%, P < 0.001), males (AAPC: 5.40%, P < 0.001), and individuals residing in rural counties and the Northeast. Cardiovascular mortality among US adults with mental health disorders increased significantly between 1999 and 2024, highlighting the persistent disparities in this vulnerable population. These findings reinforce the need for integrated cardiovascular and psychiatric care, targeted prevention strategies, and equitable access to healthcare.

Donation after circulatory death (DCD) has expanded the US heart donor pool yet carries a higher risk of severe primary graft dysfunction (PGD) for recipients compared to donation after brain death (DBD). This study addresses an important knowledge gap of exploring the role of heart size mismatch in contributing to the risk of severe PGD in DCD-HT.

All heart-only, adult transplants from the united network for organ sharing (UNOS) database were collected from 09/2023-06/2025. Univariable (UV) and multivariable (MV) analyses were used to identify associations between various size matching variables and severe PGD in both DCD-HT and DBD-HT.

In the DCD-HT MV analysis, no categorical classifications of size mismatch had significant associations with severe PGD. However, various recipient size metrics, including predicted heart mass (PHM) (OR = 1.01 per gram [1.00-1.01], p = 0.002) were independently associated with severe PGD in DCD-HT. When analyzed in the dataset containing both DCD and DBD cases, PHM's association with severe PGD was found to interact with DCD status (β = 0.009, SE = 0.0032, p = 0.004).

Conventional categorical donor-recipient size-mismatch classifications established in DBD-HT were not associated with severe PGD in DCD-HT. In contrast, larger recipient size was independently associated with an increased risk of severe PGD in DCD-HT, whereas no such association was observed in DBD-HT. These findings highlight potential differences in the determinant of severe PGD between DCD-HT and DBD-HT and support further investigation into the role of recipient size in donor-recipient matching for DCD-HT.

Prehospital stroke trials enable assessments of ultraearly administration of treatments and management strategies, but face unique challenges in their design, conduct, and analysis. We outline important considerations and recommendations for planning prehospital stroke trials, focusing on patient identification, consent models, randomization strategies, end point selection, and statistical frameworks. As this field evolves, multidisciplinary collaboration, pragmatic study design, and scalable technology integration are critical to ensuring scientific rigor and equitable access. This framework is intended to inform and support future investigators in designing effective, ethically sound, and operationally feasible prehospital stroke trials in conventional emergency medical services settings.

Dobutamine is recommended for septic shock with myocardial dysfunction and persistent hypoperfusion despite preload and mean arterial pressure optimization; however, supporting evidence is limited, and predictors of response remain unclear.

To determine whether early hemodynamic responsiveness to dobutamine is associated with clinical outcomes and whether baseline echocardiographic parameters identify responders.

Single-center retrospective cohort study at a quaternary academic medical center. Adults with septic shock who received concomitant dobutamine with vasopressor therapy and underwent transthoracic echocardiography within 12 hours before dobutamine initiation.

Hemodynamic responsiveness was defined as the combination of an increase in central venous oxygen saturation (ScvO2) of at least five percentage points and a reduction in norepinephrine-equivalent (NEE) dose measured at 2 hours after dobutamine initiation. The primary outcome was 28-day ICU mortality. Secondary outcomes included ICU-free days and renal replacement therapy (RRT) requirement.

Of 104 patients, 37 (36%) met the composite definition of hemodynamic response. Baseline demographics, illness severity, lactate, and baseline vasopressor dose were similar between groups. Beyond the 2-hour window used to define response, separation persisted at 6 hours: responders showed a greater reduction in NEE dose (ΔNEE, -0.13 vs. 0.04 µg/kg/min; p < 0.001) and a higher MAP/NEE ratio (380 vs. 166; p = 0.003), and a greater increase in ScvO2 (+12% vs. +6%; p = 0.014). 28-day ICU mortality was 41% in responders and 58% in nonresponders (p = 0.13); after multivariable adjustment, hemodynamic response was associated with lower 28-day ICU mortality (odds ratio, 0.18; 95% CI, 0.04-0.68; p = 0.018). Responders had more ICU-free days (17 [0-22] vs. 0 [0-15]; p = 0.017); RRT requirement did not differ (43% vs. 37%; p = 0.7). No baseline echocardiographic parameter was associated with hemodynamic responsiveness.

In septic shock with myocardial dysfunction, early hemodynamic responsiveness to dobutamine identified a subgroup with a more favorable clinical trajectory. Resting echocardiographic parameters did not identify responders. These findings are hypothesis-generating and require prospective confirmation.

Timely antibiotics are associated with reduced sepsis mortality, particularly among patients with hypotension; however, antibiotic delays are common in practice. Presenting symptoms may influence antibiotic timing and confound the association between antibiotic timing and outcomes.

To evaluate whether any presenting symptoms are associated with antibiotic timing and to assess risk-adjusted 30-day mortality by antibiotic timing after adjustment for symptoms.

This cohort study was conducted among adults hospitalized for community-onset presumed bacterial sepsis at 67 hospitals in the Michigan Medicine Safety Consortium from November 2020 to May 2024.

Presenting symptoms; time from hospital presentation to first antibiotic administration.

Timely antibiotics, defined as antibiotic administration within 3 hours of hospital presentation for patients with hypotension and within 5 hours for patients without hypotension, was the primary outcome. Secondary outcomes included time to antibiotics, measured as a continuous variable, and 30-day mortality.

Among 29 647 patients included in this analysis, the median (IQR) age was 71 (61-80) years, 14 676 (49.5%) were male, and the median (IQR) Charlson Comorbidity Index was 3 (1-5). Among 6704 patients (22.6%) presenting with hypotension, 4413 (65.8%) received timely antibiotics (within 3 hours). Among 22 942 (77.4%) patients presenting without hypotension, 17 544 (76.5%) received timely antibiotics (within 5 hours). In multivariable analyses, presenting symptoms were independently associated with antibiotic timing. Among patients with and without hypotension, prehospital fever was associated with increased odds of timely antibiotics (with hypotension: adjusted odds ratio [aOR], 1.34 [95% CI, 1.19 to 1.52]; without hypotension: aOR, 1.26 [95% CI, 1.17 to 1.35]), while gastrointestinal symptoms were associated with decreased odds of timely antibiotics (with hypotension: aOR, 0.84 [95% CI, 0.75 to 0.94]; without hypotension: aOR, 0.80 [95% CI, 0.75 to 0.86]). Urinary and respiratory symptoms were associated with antibiotic timing for patients without hypotension (urinary symptoms: aOR, 1.13 [95% CI, 1.05 to 1.22]; respiratory symptoms: aOR, 0.91 [95% CI, 0.85 to 0.99]). Timely antibiotics were associated with reduced 30-day mortality (adjusted absolute difference, -2.10 [95% CI, -3.01 to -1.10] percentage points) among the overall cohort, after adjustment for presenting symptoms.

In this cohort study of 29 647 adults presenting with community-onset presumed bacterial sepsis, presenting symptoms were associated with timing of antibiotic therapy. Even after adjusting for presenting symptoms, timely antibiotics remained associated with lower mortality. These findings suggest that proactive screening for sepsis among patients with less obvious clinical presentations may promote timely recognition and treatment.

Primary hyperparathyroidism (PHPT) predominantly affects women, particularly after menopause. Whether sex-related differences extend beyond epidemiology to influence the clinical expression of the disease remains incompletely understood. We investigated sex-related differences in the clinical phenotype of PHPT.

We retrospectively analyzed clinical, biochemical, imaging, and histopathological data from patients with PHPT referred to our Endocrinology Unit over a 5-year period.

A total of 315 patients were included (64 men and 251 women; female-to-male ratio 3.9:1). Mean age at diagnosis was similar between sexes (60 ± 16 vs. 59 ± 13 years, p = 0.499), and 77% of women were postmenopausal. Despite comparable mean serum calcium levels, men more frequently presented with serum calcium concentrations > 1 mg/dL above the upper limit of normal (42% vs. 29%, p = 0.042), higher urinary calcium excretion, and lower serum phosphate levels. Women showed significantly greater skeletal involvement, with a higher prevalence of osteopenia/osteoporosis (71.7% vs. 53.1%, p = 0.004), vertebral fractures (44% vs. 12%, p < 0.001), non-vertebral fragility fractures (34% vs. 12%, p = 0.003), and bone and muscle pain (60.7% vs. 10.3%, p < 0.001). Conversely, nephrolithiasis (p = 0.013) and cardiovascular comorbidities (p = 0.046) were more frequent in men. Women also displayed a less favorable metabolic profile, characterized by higher HbA1c and HOMA index values, a greater prevalence of dyslipidemia (p = 0.001), and more frequent depressive symptoms (p = 0.001) and fatigue (p = 0.040).

PHPT exhibits distinct sex-specific clinical phenotypes. Men present a more severe biochemical and cardiovascular profile, whereas women show greater skeletal involvement, a less favorable metabolic profile, and a higher burden of non-classical symptoms. These findings support a sex-specific approach to the evaluation and management of PHPT.

Retrohepatic inferior vena cava (IVC) injury is a rare but frequently fatal challenge in trauma surgery. This study describes a structured cadaveric training sequence for total hepatic vascular exclusion (THVE), including transdiaphragmatic intrapericardial IVC exposure as an alternative escalation route for suprahepatic venous control.

A structured cadaveric dissection study was performed on nine adult cadavers by a multidisciplinary team of vascular and pediatric surgeons. The motivation was derived from an index pediatric blunt trauma case involving life-threatening retrohepatic caval bleeding. Five anatomical exposure steps relevant to THVE were rehearsed sequentially: hepatoduodenal ligament control, infrahepatic IVC exposure above the renal veins, access to the suprahepatic IVC via infradiaphragmatic and transdiaphragmatic intrapericardial IVC exposure and optional supracoeliac aortic exposure. The exposure steps were performed in a fixed sequence that was identical in all nine donors; the sequence was not randomized. After each dissection, procedural difficulty for each anatomical landmark was graded using a five-point scale: 1 = very easy, 2 = easy, 3 = moderate, 4 = difficult, and 5 = very difficult.

Hepatoduodenal ligament control received the lowest difficulty ratings. Perceived difficulty of infrahepatic IVC and supracoeliac aortic exposure decreased after repeated dissections. Infradiaphragmatic suprahepatic IVC exposure remained technically demanding, whereas transdiaphragmatic intrapericardial IVC exposure received significantly lower ratings of perceived difficulty (p = .004), with lower ratings after the initial dissections.

In this cadaveric training model, transdiaphragmatic intrapericardial IVC exposure received significantly lower ratings of perceived difficulty than infradiaphragmatic suprahepatic IVC exposure. Because the order of the two approaches was fixed and difficulty was assessed by team consensus, this finding does not establish that the transdiaphragmatic route is objectively easier, safer, or clinically superior.

Doxorubicin (DOX) is a widely used anthracycline chemotherapeutic agent; however, its cumulative cardiotoxicity limits its clinical use. Oxidative stress, mitochondrial dysfunction, myocardial senescence, and fibrotic remodeling contribute to chronic DOX-induced cardiac injury. Shikonin (SKN), a natural naphthoquinone compound, possesses antioxidant and mitochondrial protective properties. However, whether SKN can attenuate DOX-induced myocardial senescence and fibrosis remains unclear.

A chronic DOX-induced cardiotoxicity model was established in male Sprague- Dawley rats, followed by treatment with SKN or captopril. Cardiac function, myocardial injury and fibrosis, oxidative stress, mitochondrial dysfunction, and senescence-associated changes were assessed using echocardiography, histological and fluorescence staining, biochemical assays, and Western blotting. Complementary DRP1 loss- and gain-of-function experiments were performed in DOX-treated H9c2 cardiomyoblasts. DOX impaired cardiac function, disrupted myocardial structure, increased collagen deposition, induced redox imbalance and mitochondrial membrane depolarization, and promoted myocardial senescence. SKN ameliorated these alterations and reduced DRP1, FIS1, P-p53, and p21 expression. In H9c2 cells, DRP1 knockdown mimicked several protective effects of SKN, whereas DRP1 overexpression partially reversed its effects on mitochondrial superoxide accumulation and senescence-associated changes.

SKN attenuates DOX-induced myocardial injury, senescence, and fibrosis. These effects are associated with improved redox and mitochondrial homeostasis and suppression of p53/p21-associated senescence signaling, with DRP1-related mitochondrial dysregulation contributing to the protective effects of SKN.

A 46-year-old female presented to her general practitioner with abdominal pain, lethargy, dyspnea and pedal edema. Computed tomography (CT) revealed features of heart and liver failure with pleural fluid and ascites and the liver having a cirrhotic appearance. A gastroenterologist confirmed the diagnosis of cirrhosis, but the etiology was unknown. Pericardial calcifications and elevated jugular venous pressure on examination gave rise to a suspicion of constrictive pericarditis as the cause of the liver cirrhosis. Cardiac catheterization confirmed pericardial constriction, and the patient underwent a total pericardiectomy.

It is easy to miss a diagnosis of constrictive pericarditis because it must be specifically sought after in the echocardiogram, and pericardial calcifications are only present in a minority of cases.

Most studies comparing Off-pump and On-pump coronary artery bypass grafting (CABG) have primarily focused on short-term outcomes. The aim of this study was therefore to evaluate and compare long-term complications and survival between these surgical approaches.

This retrospective study included 2337 patients who underwent primary isolated CABG in Iceland between 2001-2021; 397 (17,0%) performed Off-Pump and 1940 (83,0%) On-Pump. The complications stroke, myocardial infarction (MI), percutaneous coronary intervention (PCI), repeat CABG and death; combined as major adverse cardiovascular and cerebrovascular events (MACCE), were compared between the groups after 1:1 propensity score matching (377 pairs). Long-term survival and MACCE-free survival were estimated using the Kaplan-Meier method and multivariable Cox regression.

Before matching, patients in the On-Pump group had more extensive coronary artery disease and were more often operated on acutely. At 10-year follow-up, the cumulative incidence of PCI (14.0% in the Off-Pump group vs. 10.2% in the On-Pump group, p=0.110), MI (9.0% vs. 8.0%, p=0.784), stroke (4.6% vs. 6.8%, p=0.090) and repeat CABG (0.9% vs. 0.0%, p=0.090) were comparable between groups in the matched cohort. MACCE-free survival (71.0% in the Off-Pump group vs. 71.4% in the On-Pump group, p=0.74) and overall survival (78.5% vs. 73.2%, p=0.095) at 10 years was also comparable between groups. Furthermore, multivariate analysis showed similar overall survival for both surgical techniques (HR: 0.81; 95%-CI: 0.60-1.09; p=0,156).

The long-term outcomes following CABG in Iceland are favorable for both Off-pump and On-pump procedures, both in terms of survival and long-term complications.