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Sex Disparities in Acute Myocardial Infarction Diagnosis and Treatment.
No full textThis study sought to assess sex differences in timely diagnosis (time-to-ECG) and treatment (time-to-percutaneous coronary intervention (PCI)) of ST-elevation myocardial infarction (STEMI) and Non-STEMI (NSTEMI) patients utilizing a retrospective cross-sectional analysis of 1,098 STEMI (306 females and 792 males) and 2,179 NSTEMI (747 females, 1,432 males) patients that presented to 2 urban EDs between January 2022 and December 2024 was performed. Sex differences in time-to-ECG were assessed in both STEMI and NSTEMI patients, whereas differences in time-to-PCI were assessed in STEMI patients only. Time-to-ECG and time-to-PCI were compared continuously, as well as categorically (ECG delay = time-to-ECG \u3e10 min and PCI delay = time-to-PCI \u3e90 min or \u3e120 min when a transfer occurred). Median time-to-ECG was 3.0 min shorter for male STEMI and NSTEMI patients. Males also had a reduced likelihood of an ECG delay (OR: 0.64 [95% CI 0.51 to 0.82]). Sex disparities remained when assessing only patients with a chief complaint of chest pain (OR:0.74 [95% CI 0.56 to 0.97]). Male STEMI patients also had a shorter wait time for PCI compared to females (walk-in: 1:26:00 vs 1:41:00, transfer: 2:19:30 vs 2:44:30, respectively). However, sex was not a significant predictor of PCI delay after controlling for time-to-ECG. In conclusion, sex disparities were found in time-to-ECG for STEMI and NSTEMI patents, as well as time-to-PCI for STEMI patients. However, sex was not significantly associated with PCI delay after controlling for time-to-ECG. This highlights the importance of timely diagnosis to ensure timely revascularization in acute myocardial infarction patients
The LAVA Study: A Prospective, Multicenter, Single-Arm Study of a Liquid Embolic System for Treatment of Peripheral Arterial Hemorrhage.
No full textPURPOSE: To present the results of the Liquid Embolization of Arterial Hemorrhages in Peripheral Vasculature (LAVA) study evaluating safety and effectiveness of Lava Liquid Embolic System, an ethylene vinyl alcohol (EVOH), for peripheral arterial hemorrhage (PAH).
MATERIALS AND METHODS: LAVA was a pivotal, prospective, multicenter, single-group, centrally adjudicated study of adults with active PAH. Patients received EVOH at 1 of 2 viscosities, administered by experienced physicians. The primary safety endpoint was freedom from 30-day major adverse events (MAEs) defined as ischemia/infarction of target territory, non-target embolization, allergic reaction, and catheter breakage/entrapment. The primary effectiveness endpoint was 30-day clinical success defined as absence of bleeding from target lesion after embolization without need for emergency surgery, re-embolization, or other target lesion reinterventions. The secondary endpoints included serious adverse events and mortality.
RESULTS: A total of 113 patients (mean age, 57.4 years [SD ± 18.0; range, 18.0-93.0 years]; male, 63.7%) with 148 lesions were enrolled at 19 US centers. Targeted areas included the nongastrointestinal visceral arteries (31.1%), kidneys (26.3%), upper gastrointestinal (GI) (11.5%), lower GI (6.8%), and extremities (6.1%). Empiric embolization was performed for 20.9% of lesions. The primary effectiveness endpoint was achieved in 94.3% of lesions (95.3% of patients), exceeding the performance goal of 72%. Two target lesions treated with EVOH required subsequent re-embolization. No surgeries were performed for bleeding or ischemia. There were no MAEs reported per study definition. All-cause mortality rate at 30 days was 8.3%.
CONCLUSIONS: The LAVA study suggests that EVOH is effective and can be safely used as an embolic agent for treatment of PAH
The current landscape of single-port robotic surgery in urology.
No full textThe advent of the purpose-built da Vinci single-port robotic platform marks a pivotal advancement in minimally invasive urological surgery. Designed to overcome the ergonomic and technical limitations of prior single-site approaches, the single-port system enables complex procedures through a single incision, with enhanced dexterity, optimized use of confined spaces and improved cosmetic and peri-operative outcomes. The single-port system has been increasingly used across a wide range of urological indications, including robot-assisted radical prostatectomy, partial nephrectomy, nephroureterectomy and reconstructive surgeries such as pyeloplasty and ureteral re-implantation. Innovative access strategies, such as the single-port transvesical and low anterior access approaches, have facilitated regionalized and multi-quadrant surgeries without the need for repositioning or robot re-docking. These advances have translated into reduced morbidity, faster recovery and increased feasibility of opioid-sparing, same-day discharge protocols. As surgical expertise deepens and technology evolves, the single-port robotic platform stands as a refinement of minimally invasive surgery, and also as a potential paradigm shift in urological practice
A Robust Serum Proteomic Signature of the E2 Allele of Apolipoprotein E.
No full textA signature of 16 serum proteins that were previously profiled using the aptamer-based Somascan technology highlighted the roles of the e2 allele of APOE in lipid regulation via apolipoprotein B (APOB) and apolipoprotein E (APOE) and in inflammation. Here, the serum protein signature of APOE is validated and expanded using a combination of mass-spectrometry, ELISA, Luminex, blood transcriptomics, and antibody-based Olink serum proteomics. Some of the findings were replicated in the UK Biobank using antibody-based Olink serum proteomics. This analysis replicated the association between APOB and the e2 allele of APOE, detected a new, robust pattern of association between APOE genotypes and the serum level of APOE, and discovered new associations between APOE genotypes and the complex of apolipoproteins APOC1, APOC2, APOC3, APOC4, APOE, APOF, and APOL1. In addition, 13 new proteins correlated with APOE genotypes. This extended signature includes granule proteins CAMP, CTSG, DEFA3, and MPO secreted from neutrophils and points to olfactomedin 4 (OLFM4) as a new target for the prevention of Alzheimer\u27s disease
Improving immunotherapy responses by dual inhibition of macrophage migration inhibitory factor and PD-1.
No full textMacrophage migration inhibitory factor (MIF) is an upstream regulatory cytokine that is associated with advanced disease and poor outcomes in multiple cancer types, including melanoma. We investigated whether anti-MIF therapy could enhance the antitumor effects of the immune checkpoint inhibitor anti-programmed cell death 1 (anti-PD-1) in 2 murine tumor models. The therapeutic efficacy of anti-MIF, alone or combined with anti-PD-1, was tested in the YUMMER1.7 melanoma and MC38 colorectal cancer models. Tumor growth and survival were assessed in untreated Mif-knockout (KO) and low-expression human MIF allele (CATT5) mice and compared with wild-type (WT) or high-expression MIF allele (CATT7) mice. Tumor-bearing animals underwent cytokine profiling, tumor immunohistochemistry, flow cytometry, and scRNA-Seq. We also correlated functional variant MIF alleles with melanoma incidence and progression in patients. Our results showed that combined anti-MIF and anti-PD-1 significantly reduced tumor growth, improved survival, and promoted tumor regression, accompanied by enhanced TH1 cytokine levels, increased macrophage activation-related cytokines, and increased type 1 conventional dendritic cells. scRNA-Seq analysis revealed an expansion of intratumor Cd74/C1q/Aif1-expressing macrophages, which exhibited an antitumor phenotype, in response to anti-MIF therapy. MIF-KO and CATT5 mice exhibited reduced tumor burdens compared with WT or CATT7 mice alone and in the presence of anti-PD-1. In patients with melanoma, the high-MIF expression genotype (-173C/C) occurred at higher frequencies compared with healthy controls. These findings highlight that the addition of anti-MIF to anti-PD-1 reduces tumor growth, enhances antitumor responses, prolongs survival, and augments key intratumor immune cell populations involved in immune activation against tumors. This approach merits further consideration for clinical trial development
Consensus definitions of complex-to-manage and treatment-refractory psoriatic arthritis: a GRAPPA initiative.
No full textDespite advances in the treatment of psoriatic arthritis (PsA), a substantial proportion of patients continue to report persistent symptoms and impaired quality of life. However, terminology remains inconsistent for patients who fail to achieve disease control despite treatment, which limits research comparability and contributes to therapeutic inertia. To address this gap, a Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) task force developed consensus definitions for two distinct states: complex-to-manage PsA (C2M-PsA) and treatment-refractory PsA (TR-PsA). C2M-PsA is defined as a state of persistent symptoms despite treatment with at least one biologic or targeted synthetic DMARD (b/tsDMARD), extending beyond biological non-response to include factors such as comorbidities, overlapping conditions, psychosocial burden and treatment-related challenges (for example, non-adherence). TR-PsA, a more specific subset of C2M-PsA, is characterized by failure of at least three therapies with distinct mechanisms of action (including at least two biologic/targeted synthetic DMARDs), persistent symptoms considered problematic by both patient and clinician, and objective evidence of ongoing inflammation - after ruling out alternative explanations for treatment refractoriness. These consensus-derived GRAPPA definitions provide a shared framework to standardize terminology, support individualized care, and improve patient stratification in research and practice. Prospective validation across diverse settings and phenotypes is needed to confirm their reliability, responsiveness and clinical utility
Action Collaborative on Traumatic Brain Injury Care: Adapted Clinical Practice Guideline.
No full textOutpatient follow-up care for traumatic brain injury (TBI) is inconsistent. The Action Collaborative on TBI Care, convened under the auspices of the National Academies of Sciences, Engineering, and Medicine, aimed to standardize management with a clinical practice guideline. The guideline is intended for community-dwelling adults with TBI who are able to care for themselves at hospital discharge or who did not require acute hospital care. Guideline topics were selected and prioritized with input from individuals with lived experience and clinicians. Existing evidence-based clinical practice guidelines (k = 18) were identified from systematic literature reviews. Recommendations for each priority topic were extracted from existing guidelines and synthesized using the ADAPTE process. Strength of evidence ratings were assigned based on the American Academy of Family Physician\u27s adaptation of GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) through consensus voting. A draft guideline underwent external review by 20 health professional and brain injury organizations. The Action Collaborative on TBI Care guideline provides recommendations for 11 priority topics: (1) confirm the diagnosis; (2) determine whether emergency department evaluation is required; (3) request neuroimaging and neuropsychological assessment when indicated; (4) screen for social determinants of health; (5) provide guidance on return to usual activities; (6) educate the patient and family; (7) assess for risk of persistent symptoms; (8) prioritize which symptoms to target first; (9) initiate treatment for posttraumatic headache; (10) screen and initiate treatment for mental health disorders; and (11) decide if and when to refer to specialty care
Exploratory Analysis of the Impact of a Single Dose of Trastuzumab on the Immune Microenvironment in HER2-Positive Early-Stage Breast Cancer.
No full textFacilitators and challenges in the implementation of the Care Ecosystem at six clinical sites in the United States: A qualitative study.
No full textINTRODUCTION: Collaborative care models with care navigation bridge medical and social needs in dementia care. These models, including the Care Ecosystem (CE), are being implemented at health systems and community-based programs across the United States.
METHODS: Interdisciplinary team members from six early adopter CE programs were interviewed about the facilitators and challenges they faced implementing the CE. Interviews were analyzed thematically.
RESULTS: Implementation facilitators included the presence of a champion or visionary, a clinical team with expertise in dementia, easy access to CE care protocols and consultative support, and flexibility in being able to modify the program to meet site-specific needs. Challenges centered on program launch, personnel turnover, reaching people from historically marginalized communities or those facing structural barriers to care, and program sustainability.
DISCUSSION: This study provides practical information to guide successful implementation of effective dementia care from research to practice.
HIGHLIGHTS: Collaborative care models with care navigation bridge medical and social needs in dementia care. Implementation facilitators included a champion, an expert clinical team, and flexibility. Challenges included program launch, personnel turnover, and program sustainability. Findings can guide implementation of effective dementia care from research to practice
