Washington Hospital

Circulating microRNAs are promising biomarkers of acute cellular rejection (ACR) and antibody-mediated rejection (AMR) in heart transplantation. The study objective was to assess the characteristics and diagnostic performance of previously identified microRNAs and clinical rejection scores (CRS) in distinct blood samples obtained at the time of an endomyocardial biopsy (EMB). In the 5-center, prospective, longitudinal cohort study, GRAfT (Genomic Research Alliance for Transplantation), microRNA sequencing was performed on blood samples. The previously identified microRNAs associated with ACR (n=12) and AMR (n=17) were used to fit a logistic regression model to the current cohort, and the scores were scaled from 0 to 100. Diagnostic performance of ACR and AMR microRNA panels was assessed by the area under the receiver-operating characteristic curve. An adjusted Cox proportional hazard model evaluated the effect of CRS on long-term outcomes. In 173 heart transplant recipients (29% female sex, 41% Black race, median follow-up 374 days after transplant), 922 blood samples were sequenced, 720 paired with EMB. Among 14 episodes of ACR, the median ACR CRS was 78 compared with 42 without ACR, P<0.001. Among 25 episodes of AMR, median AMR CRS was 75 compared with 53 without AMR, P<0.001. The area under the receiver-operating characteristics curve for the CRS was 0.93 for ACR and 0.92 for AMR. Using a CRS threshold of 65, the ACR CRS had 79% sensitivity, 97% specificity, and 100% negative predictive value; the AMR CRS had 84% sensitivity, 86% specificity, and 99% negative predictive value. The ACR and AMR CRS were both <65 in 589 (82%) of the tests. After adjustment, a 10-point increase in CRS was associated with >40% increase in the hazard of the composite outcome: subsequent ACR or AMR by EMB, allograft dysfunction, or death (ACR hazard ratio, 1.42 [95% CI, 1.20-1.69]; P<0.001; AMR hazard ratio, 1.45 [95% CI, 1.14-1.86]; P=0.003). Circulating microRNAs reliably identified ACR and AMR on EMB. An elevated microRNA CRS was associated with an increased risk of subsequent rejection, allograft dysfunction, or death. This biomarker, with further validation, can serve as a noninvasive test to screen and diagnose ACR and AMR without the need for an EMB. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.

Background:The Mediterranean diet (MD) and low-fat diet (LFD) were well-known dietary interventions for cardiovascular disease prevention. However, there is an ongoing debate about the relative efficacy of improving cardiovascular (CV) risk factors and clinical outcomes between the 2. This systematic review aims to evaluate and summarize findings from randomized controlled trials (RCTs) that directly compare the MD and LFD concerning CV risk factors and clinical outcomes.Methods:Per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a comprehensive literature search was conducted across PubMed, Google Scholar, SCOPUS, Science Direct, and RCTs that compared MD and LFD in adults, and reported data on CV risk factors or clinical outcomes were included.Results:Our systematic review includes 11 RCTs with 5942 participants. MD significantly reduced the formation of procoagulant and prothrombotic microvesicles. Studies have also reported that MD has resulted in greater reductions in total cholesterol, cholesterol-high-density lipoproteins ratios, insulin levels, blood glucose levels, leukocyte count, and body mass index compared to LFD.Conclusion:MD demonstrates superior efficacy over LFD in improving CV risk factors and outcomes. These findings could support the preferential recommendation of MD over LFD for the secondary prevention of cardiovascular diseases. Further research should explore the long-term adherence and implementation of these dietary interventions in diverse populations.

Abstract Background cUTIs remain a significant cause of hospital admissions and are an economic burden. IV-FOS is a first-in-class injectable epoxide antibiotic under development. A randomized trial (RCT) comparing IV-FOS to piperacillin-tazobactam (PIP-TAZ) in patients suffering from cUTIs demonstrated noninferiority with 64.7% of IV-FOS vs 54.5% of PIP-TAZ groups achieving a favorable response. We sought to compare outcomes within two subgroups: 1) patients with a high burden of chronic illness, and 2) patients with severe acute disease.Table 1.Clinical, Microbiological and Overall Response for Patients meeting SIRs Criteria or a CCI of ≥ 3 (m-MITT population) Methods Two subgroup analyses of the phase 2/3 RCT of IV-FOS vs PIP-TAZ were conducted. A composite of clinical response, defined as both clinical success and microbiologic eradication, within the microbiologic-modified intention to treat (m-MITT) population, served as the primary endpoint. High chronic illness burden was defined as a Charlson co-morbidity index (CCI) &amp;gt; 3, while severe acute disease was based on meeting criteria for the systemic inflammatory response syndrome (SIRS). Results Of 465 patients randomized, 362 (77.8%; 184 IV-FOS and 178 PIP-TAZ) constituted the m-MITT population. Within this group, 140 (38.7%; 37.5% IV-FOS vs 39.9% PIP-TAZ) had a CCI ≥ 3 and 114 (31.5%; 33.7% IV-FOS vs 29.2% PIP-TAZ) met the SIRS criteria. In unadjusted analyses, clinical response rates were similar between IV-FOS and PIP-TAZ in the two treatment groups among both patients with CCI ≥ 3 (49.3% IV-FOS vs 40.8% PIP-TAZ, p=NS) and those with SIRS (66.1% IV-FOS vs 75% PIP-TAZ, p=NS). For both subgroups, the individual components of the composites of clinical response as a function of study drug behaved similarly (Table 1). Conclusion In this Phase 2/3 RCT in cUTI, subgroup analyses in patients with SIRS and those with high burdens of chronic illness demonstrated comparable composite outcomes between IV-FOS and PIP-TAZ treatments. Disclosures Andrew Shorr, MD, MPH, MBA, Bioversys: Advisor/Consultant Keith S. Kaye, MD, MPH, AbbVie: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant Marya D. Zilberberg, MD, MPH, Basilea Pharmaceutica: Grant/Research Support|Eagle Pharmaceuticals: Advisor/Consultant|Eagle Pharmaceuticals: Grant/Research Support|Shionogi: Advisor/Consultant Judith N. Steenbergen, PhD, AcurX: Advisor/Consultant|Basilea: Advisor/Consultant|Bioversys: Advisor/Consultant|Clarametyx: Advisor/Consultant|Eagle Pharmaceuticals: Advisor/Consultant|F2G: Advisor/Consultant|Genentech: Advisor/Consultant|Innoviva: Advisor/Consultant|Meitheal: Advisor/Consultant|Melinta: Advisor/Consultant|Neuraptive: Advisor/Consultant|Neuraptive: Advisor/Consultant|Roche: Advisor/Consultant|Wockhardt: Advisor/Consultant Lauren Bjork, PharmD, Meitheal: employee Mauricio Rodriguez, PharmD, MS-HEOR, BCCCP, BCIDP, Meitheal Pharmaceuticals: employee

Acute myocardial infarction with cardiogenic shock (AMI-CS) remains highly fatal despite advances in revascularization and intensive care. The Impella, a micro-axial pump, offers a potential balance of hemodynamic support and minimal invasiveness. This study examined its optimal configuration of low- versus high-capacity for effectiveness and safety. We conducted a systematic review and pooled analysis of 20 studies, including three randomized controlled trials (RCTs) and 3896 AMI-CS patients, comparing high-capacity (Impella 5.0/5.5) versus low-capacity (Impella 2.5/CP) devices. The primary outcome was in-hospital or 30-day mortality, with secondary endpoints including mortality on support, ischemic and bleeding complications, acute kidney injury requiring renal replacement therapy (RRT), and hemolysis. Among the included patients, 2022 received low-capacity Impella, while 771 received high-capacity Impella. The high-capacity Impella group demonstrated lower in-hospital or 30-day mortality (41.4% vs. 45.4%; p = 0.045) and significantly reduced mortality on support (17.9% vs. 46.1%; p < 0.001). Major bleeding events (1.4% vs. 6.0%; p < 0.001) and ischemic complications (3.9% vs. 5.9%; p = 0.05) were also lower in the high-capacity group. However, transfusion requirements were higher in the high-capacity Impella cohort (52.1% vs. 23.1%; p < 0.001). There were no significant differences in stroke rates (4.3% vs. 4.3%; p = 1.0) or AKI requiring RRT (36.5% vs. 34.9%; p = 0.69). High-capacity Impella, when compared to low-capacity devices, may provide superior survival benefits and lower complication rates, particularly in reducing ischemic and major bleeding events, in AMI-CS patients. These findings support the early consideration of high-capacity Impella in treatment algorithms.

There is a paucity of data regarding the longer-term durability of transcatheter heart valves. This analysis aimed to describe the 5-year clinical outcomes and valve durability for patients treated with the Portico transcatheter heart valves across 3 studies harmonized in their prospective enrollment, inclusion/exclusion criteria, centralized independent core laboratory echocardiographic analysis, and independent clinical events committee adjudication. Patient-level data from the PORTICO IDE randomized controlled trial, the PORTICO I postmarket study, and the PORTICO continued access protocol were pooled using a random-effects meta-analysis model. All 3 studies collected follow-up data at discharge, 30 days, and annually through 5 years. Adverse events and pooled echocardiographic data were assessed using Valve Academic Research Consortium-2 definitions. Durability definitions were adapted from Valve Academic Research Consortium-3 and European Association of Percutaneous Cardiovascular Interventions/European Society of Cardiology/European Association for Cardio-Thoracic Surgery consensus guidelines. A total of 1464 patients with severe symptomatic aortic stenosis and high or extreme surgical risk were included. Median age was 83 years, 61.7% were women, and the median Society of Thoracic Surgeons score was 4.9%. At 5 years, all-cause mortality and stroke rates were 49.4% and 12.3%, respectively. Transvalvular gradient and effective orifice area at 5 years were 6.2 mm Hg and 1.83 cm2, respectively, with paravalvular leak ≥moderate severity occurring in 1.9%. The 5-year bioprosthetic valve failure rate was 2.7%, including a 0.7% valve-related death rate and a 2.0% valve reintervention rate, but no patients with severe hemodynamic structural valve deterioration. Moderate hemodynamic structural valve deterioration occurred in 0.9% of the patients at 5 years. Hemodynamic performance and transcatheter heart valve durability remained stable irrespective of annular size. The use of the Portico transcatheter heart valve system in patients at high or extreme surgical risk demonstrated favorable clinical outcomes and hemodynamic performance with low transvalvular gradients and greater than mild paravalvular leak. Furthermore, bioprosthetic valve failure rates were low with no incidence of severe hemodynamic structural valve deterioration at 5 years, irrespective of annular size. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02000115 and NCT01802788.

The Safe Babies Safe Moms Women's and Infants' Services Perinatal Mental Health and Wellness Program offers screening, assessment, prevention, and treatment options, as well as referrals, for complex care needs using an integrated collaborative care framework. Group and individual therapy options are available, leveraging both office-based and telehealth options. The article details the program's framework for services, describes the care team and program workflow, and summarizes program activities. In calendar year 2024, 3383 screenings using the Edinburgh Postnatal Depression Scale were completed for 1914 unique patients. Perinatal social workers conducted 1328 care coordination visits and completed 148 perinatal mental health assessments for elevated screenings. Integrated therapeutic services reached 220 people, and 53 were referred to psychiatry for complex care needs. The strengths of this program stem from early initiation of screening, multiple screenings throughout the perinatal period, care coordination for social services interventions, and a shared-decision-making process centered around the patients' needs and goals for perinatal mental health care. This integrated mental health model establishes a distinct, well-defined, yet dynamic pathway to provide screening, care coordination, and interventions for both prevention and treatment to optimize perinatal mental health outcomes. Evaluation of program outcomes is ongoing.