Myocardial strain is associated with adverse cardiac events in patients treated with chimeric antigen receptor (CAR) T-cell therapy.

BACKGROUND: Cardiovascular events, including heart failure and arrhythmias, following chimeric antigen receptor (CAR) T-cell therapy are increasingly recognized. Although global longitudinal strain (GLS) has demonstrated prognostic utility for other cancer therapy-related cardiac dysfunction, less is known regarding the association of GLS with adverse cardiac events following CAR T-cell therapy. OBJECTIVES: To determine the association of baseline GLS with adverse cardiovascular events in adults receiving CAR-T cell therapy. METHODS: Patients who had an echocardiogram within 6 months prior to receiving CAR T-cell therapy were retrospectively identified. Clinical data and cardiac events were collected via chart review. Echocardiograms were analyzed offline for GLS, left ventricular ejection fraction, and Doppler parameters. Multivariable logistic regression was used to determine the association between adverse cardiovascular events and echocardiographic parameters. RESULTS: Among 75 CAR T-cell therapy patients (mean age 63.9, 34.7% female), nine patients (12%) experienced cardiac events (CEs) including cardiovascular death, new/worsening heart failure, and new/worsening arrhythmia within 1 year of treatment. In univariable models, higher baseline GLS (OR 0.78 [0.63, 0.96], p = .021) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.40 [1.08, 1.81], p = .012) was associated with a higher risk of CE. After adjusting for age and LDH, higher baseline GLS (OR 0.65 [0.48-0.88], p = <.01) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.56 [1.06, 2.29], p = .024) was associated with a higher risk of CE. CONCLUSION: Lower GLS and higher mitral E/e' on a baseline echocardiogram were associated with higher risk for CEs in patients receiving CAR T-cell therapy.

Interventions and contextual factors to improve retention in care for patients with hypertension in primary care: Hermeneutic systematic review.

BACKGROUND: Regular engagement over time in hypertension care, or retention, is a crucial but understudied step in optimizing patient outcomes. This systematic review leverages a hermeneutic methodology to identify, evaluate, and quantify the effects of interventions and contextual factors for improving retention for patients with hypertension. METHODS: We searched for articles that were published between 2000 and 2022 from multiple electronic databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, clinicaltrials.gov, and WHO International Trials Registry. We followed the latest version of the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline to report the findings for this review. We also synthesized the findings using a hermeneutic methodology for systematic reviews, which used an iterative process to review, integrate, analyze, and interpret evidence. RESULTS: From 4686 screened titles and abstracts, 18 unique studies from 9 countries were identified, including 10 (56%) randomized controlled trials (RCTs), 3 (17%) cluster RCTs, and 5 (28%) non-RCT studies. The number of participants ranged from 76 to 1562. The overall mean age range was 41-67 years, and the proportion of female participants ranged from 0% to 100%. Most (n = 17, 94%) studies used non-physician personnel to implement the proposed interventions. Fourteen studies (78%) implemented multilevel combinations of interventions. Education and training, team-based care, consultation, and Short Message Service reminders were the most common interventions tested. CONCLUSIONS: This review presents the most comprehensive findings on retention in hypertension care to date and fills the gaps in the literature, including the effectiveness of interventions, their components, and contextual factors. Adaptation of and implementing HIV care models, such differentiated service delivery, may be more effective and merit further study. REGISTRATION: CRD42021291368. PROTOCOL REGISTRATION: PROSPERO 2021 CRD42021291368. Available at: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=291368.

Clinical characteristics and treatment patterns of pregnant women with hypertension in primary care in the Federal Capital Territory of Nigeria: cross-sectional results from the hypertension treatment in Nigeria Program.

BACKGROUND: Hypertensive disorders of pregnancy, including hypertension, are a leading cause of maternal mortality in Nigeria. However, there is a paucity of data on pregnant women with hypertension who receive care in primary health care facilities. This study presents the results from a cross-sectional analysis of pregnant women enrolled in the Hypertension Treatment in Nigeria Program which is aimed at integrating and strengthening hypertension care in primary health care centres. METHODS: A descriptive analysis of the baseline results from the Hypertension Treatment in Nigeria Program was performed. Baseline blood pressures, treatment and control rates of pregnant women were analysed and compared to other adult women of reproductive age. A complete case analysis was performed, and a two-sided p value < 0.05 was considered statistically significant. RESULTS: Between January 2020 to October 2022, 5972 women of reproductive age were enrolled in the 60 primary healthcare centres participating in the Hypertension Treatment in Nigeria Program and 112 (2%) were pregnant. Overall mean age (SD) was 39.6 years (6.3). Co-morbidities were rare in both groups, and blood pressures were similar amongst pregnant and non-pregnant women (overall mean (SD) first systolic and diastolic blood pressures were 157.4 (20.6)/100.7 (13.6) mm Hg and overall mean (SD) second systolic and diastolic blood pressures were 151.7 (20.1)/98.4 (13.5) mm Hg). However, compared to non-pregnant women, pregnant women had a higher rate of newly diagnosed hypertension (65.2% versus 54.4% p = 0.02) and lower baseline walk-in treatment (32.1% versus 42.1%, p = 0.03). The control rate was numerically lower among pregnant patients (6.3% versus 10.2%, p = 0.17), but was not statistically significant. Some pregnant patients (8.3%) were on medications contraindicated in pregnancy, and none of the pregnant women were on aspirin for primary prevention of preeclampsia. CONCLUSIONS: These findings indicate significant gaps in care and important areas for future studies to improve the quality of care and outcomes for pregnant women with hypertension in Nigeria, a country with the highest burden of maternal mortality globally.

Echocardiographic correlates of major adverse cardiac events at 1 year in patients with apical ballooning takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction and associated with considerable morbidity and mortality. We sought to evaluate the association between change in cardiac mechanics after diagnosis of TTS with 1-year incidence of major adverse cardiovascular events (MACE). METHODS: We retrospectively identified 85 patients with apical TTS based on ICD 9/10 codes and chart adjudication, who had a follow-up echocardiogram within 6 months of diagnosis. Echocardiograms were analyzed for left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), GLS ratio, global circumferential strain (GCS), and global radial strain (GRS). Multivariable logistic regression was performed to identify parameters associated with MACE (all-cause mortality, heart failure, stroke, and coronary artery disease [CAD] requiring percutaneous coronary intervention [PCI]) at 1 year. Event-free survival was assessed in patients with GLS (≤-18% vs. >18%) and LVEF (≥53% vs. <53%). RESULTS: Within 1 year of diagnosis, MACE occurred in 15 (18%) patients. Between baseline and follow-up echocardiogram (median 15 [range 1-151] days), there were significant differences in change in LVEF and GLS in patients with versus without incident MACE. In multivariate analysis, change in LVEF (odds ratio [OR] = .93 [.87, .98], p = .013) and change in GLS (OR = 1.32 [1.04, 1.67], p = .022) were independently associated with MACE; however, the association with change in GLS was attenuated (odds ratio [OR] = 1.13 [.94, 1.36], p = .21) after adjustment for baseline and change in LVEF. Among patients with normalized LVEF at follow-up, there were five (14.7%) MACE; whereas, there were no events among patients with normalized GLS. CONCLUSIONS: In patients with apical TTS, recovery in GLS and LVEF at follow-up was associated with significantly lower MACE at 1 year. Normalization of GLS at follow-up was better able to discriminate event-free survival than normalization of LVEF.

Eligibility and Prevalence of the American Heart Association Heart Check Certification Program in the US Packaged Food and Beverage Supply: A Cross-Sectional Study.

Objective: Consumers in the US make choices within a food supply dominated by processed packaged foods and beverage products. Front-of-package nutrition labels (FOPL) equip consumers to make healthier choices, but further evaluation and regulation regarding FOPL format, scope, and display have been recommended by the World Health Organization. As a leader in consumer FOPL guidance, the American Heart Association's (AHA) Heart Check programme certifies food companies seeking to add an AHA Heart Check logo as a FOPL for qualifying heart healthy products. A cross-sectional assessment of the AHA Heart Check Standard Certification was conducted within the US packaged food and beverage supply to assess the eligibility and prevalence of the programme as a FOPL. Methods: Data were derived from Label Insight's Open Data initiative, which is the largest publicly-available US branded food composition database. The proportions of products that were certified and eligible to be certified for the Standard Certification were reported by nutrient attributes, grocery aisles and food brands. Results: Among 153,453 products examined, fewer than 1% exhibited the Heart Check certification on their label. Among products that were not Heart Check certified,13.8% were eligible for Standard Certification. The most common reason for ineligibility was the saturated fat content (52%), followed by total fat content (47%) and sodium content (47%). Heart Check certification and eligibility differed substantially across grocery aisle categories. Conclusions: The abundance of unhealthy products in the US packaged food and beverage supply and absence of harmonized FOPL policies suggest the need for FOPL like the Heart Check label to promote adherence to healthy diets. There are opportunities for food manufacturers and the AHA to certify more heart healthy foods and beverages. However, more consistent criteria and transparent labelling could enhance Heart Check certification to facilitate consumers' ability to make more informed and healthful purchases.

Efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA): Rationale and design for a randomized controlled trial.

BACKGROUND: Over half of patients with elevated blood pressure require multi-drug treatment to achieve blood pressure control. However, multi-drug treatment may lead to lower adherence and more adverse drug effects compared with monotherapy. OBJECTIVE: The Quadruple Ultra-low-dose Treatment for Hypertension (QUARTET) USA trial was designed to evaluate whether initiating treatment with ultra-low-dose quadruple-combination therapy will lower office blood pressure more effectively, and with fewer side effects, compared with initiating standard dose monotherapy in treatment naive patients with SBP < 180 and DBP < 110 mm Hg and patients on monotherapy with SBP < 160 and DBP < 100 mm Hg. METHODS/DESIGN: QUARTET USA was a prospective, randomized, double-blind trial (ClinicalTrials.gov NCT03640312) conducted in federally qualified health centers in a large city in the US. Patients were randomly assigned (1:1) to either ultra-low-dose quadruple combination therapy or standard dose monotherapy. The primary outcome was mean change from baseline in office systolic blood pressure at 12-weeks, adjusted for baseline values. Secondary outcomes included measures of blood pressure change and variability, medication adherence, and health related quality of life. Safety outcomes included occurrence of serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. A process evaluation aimed to understand provider experiences of implementation and participant experiences around side effects, adherence, and trust with clinical care. DISCUSSION: QUARTET USA was designed to evaluate whether a novel approach to blood pressure control would lower office blood pressure more effectively, and with fewer side effects, compared with standard dose monotherapy. QUARTET USA was conducted within a network of federally qualified healthcare centers with the aim of generating information on the safety and efficacy of ultra-low-dose quadruple-combination therapy in diverse groups that experience a high burden of hypertension.

Capacity and site readiness for hypertension control program implementation in the Federal Capital Territory of Nigeria: a cross-sectional study.

BACKGROUND: Nigeria faces an increase in the burden of non-communicable diseases (NCDs), including cardiovascular diseases (CVDs), leading to an estimated 29% of all deaths in the country. Nigeria has an estimated hypertension prevalence ranging from 25 to 40% of her adult population. Despite this high burden, awareness (14-30%), treatment (< 20%), and control (9%) rates of hypertension are low in Nigeria. Against this backdrop, we sought to perform capacity and readiness assessments of public Primary Healthcare Centers (PHCs) to inform Nigeria's system-level hypertension control program's implementation and adaptation strategies. METHODS: The study employed a multi-stage sampling to select 60 from the 243 PHCs in the Federal Capital Territory (FCT) of Nigeria. The World Health Organization (WHO) Service Availability and Readiness Assessment was adapted to focus on hypertension diagnosis and treatment and was administered to PHC staff from May 2019 - October 2019. Indicator scores for general and cardiovascular service readiness were calculated based on the proportion of sites with available amenities, equipment, diagnostic tests, and medications. RESULTS: Median (interquartile range [IQR]) number of full-time staff was 5 (3-8), and were predominantly community health extension workers (median = 3 [IQR 2-5]). Few sites (n = 8; 15%) received cardiovascular disease diagnosis and management training within the previous 2 years, though most had sufficient capacity for screening (n = 58; 97%), diagnosis (n = 56; 93%), and confirmation (n = 50; 83%) of hypertension. Few PHCs had guidelines (n = 7; 13%), treatment algorithms (n = 3; 5%), or information materials (n = 1; 2%) for hypertension. Most sites (n = 55; 92%) had one or more functional blood pressure apparatus. All sites relied on paper records, and few had a functional computer (n = 10; 17%) or access to internet (n = 5; 8%). Despite inclusion on Nigeria's essential medicines list, 35 (59%) PHCs had zero 30-day treatment regimens of any blood pressure-lowering medications in stock. CONCLUSIONS: This first systematic assessment of capacity and readiness for a system-level hypertension control program within the FCT of Nigeria demonstrated implementation feasibility based on the workforce, equipment, and paper-based information systems, but a critical need for essential medicine supply strengthening, health-worker training, and protocols for hypertension treatment and control in Nigeria.

Differences in the sodium content of bread products in the USA and UK: implications for policy.

OBJECTIVE: Americans consume Na in excess of daily recommendations. Most dietary Na comes from packaged foods, and bread is a major contributor. In the UK, national Na reduction strategies contributed to lower Na levels in packaged foods and lower population Na intake. Similar initiatives are emerging in the USA and require surveillance to assess effectiveness. We aimed to examine Na levels in bread products in the USA and compare levels with similar UK products. DESIGN: Na data for bread products were obtained from the US Label Insight Open Data Initiative (n 4466) and the FoodSwitch UK database (n 1651). Mean, median and range of Na content, and proportion of products meeting Na targets established by the National Salt Reduction Initiative (NSRI) and the UK Department of Health (DH) were calculated overall, by bread type and by country. RESULTS: Mean (sd) Na content in bread was 455 (170) mg/100 g in the USA and 406 (179) mg/100 g in the UK. In both countries, savoury bread had the highest mean Na (USA=584 mg/100 g, UK=543 mg/100 g) and fruit bread the lowest mean Na (USA=345 mg/100 g, UK=277 mg/100 g). Na content of US bread products was 12 % higher than in the UK, with 21 % of US bread products and 31 % of UK bread products meeting the NSRI and DH targets, respectively. CONCLUSIONS: US bread products have, on average, 12 % more Na than similar products in the UK. Variation in Na content within product categories, and between countries, suggests the feasibility of manufacturing products with lower Na to lower dietary Na intake.

Effect of a Quality Improvement Intervention on Clinical Outcomes in Patients in India With Acute Myocardial Infarction: The ACS QUIK Randomized Clinical Trial.

Importance: Wide heterogeneity exists in acute myocardial infarction treatment and outcomes in India. Objective: To evaluate the effect of a locally adapted quality improvement tool kit on clinical outcomes and process measures in Kerala, a southern Indian state. Design, Setting, and Participants: Cluster randomized, stepped-wedge clinical trial conducted between November 10, 2014, and November 9, 2016, in 63 hospitals in Kerala, India, with a last date of follow-up of December 31, 2016. During 5 predefined steps over the study period, hospitals were randomly selected to move in a 1-way crossover from the control group to the intervention group. Consecutively presenting patients with acute myocardial infarction were offered participation. Interventions: Hospitals provided either usual care (control group; n = 10 066 participants [step 0: n = 2915; step 1: n = 2649; step 2: n = 2251; step 3: n = 1422; step 4; n = 829; step 5: n = 0]) or care using a quality improvement tool kit (intervention group; n = 11 308 participants [step 0: n = 0; step 1: n = 662; step 2: n = 1265; step 3: n = 2432; step 4: n = 3214; step 5: n = 3735]) that consisted of audit and feedback, checklists, patient education materials, and linkage to emergency cardiovascular care and quality improvement training. Main Outcomes and Measures: The primary outcome was the composite of all-cause death, reinfarction, stroke, or major bleeding using standardized definitions at 30 days. Secondary outcomes included the primary outcome's individual components, 30-day cardiovascular death, medication use, and tobacco cessation counseling. Mixed-effects logistic regression models were used to account for clustering and temporal trends. Results: Among 21 374 eligible randomized participants (mean age, 60.6 [SD, 12.0] years; n = 16 183 men [76%] ; n = 13 689 [64%] with ST-segment elevation myocardial infarction), 21 079 (99%) completed the trial. The primary composite outcome was observed in 5.3% of the intervention participants and 6.4% of the control participants. The observed difference in 30-day major adverse cardiovascular event rates between the groups was not statistically significant after adjustment (adjusted risk difference, -0.09% [95% CI, -1.32% to 1.14%]; adjusted odds ratio, 0.98 [95% CI, 0.80-1.21]). The intervention group had a higher rate of medication use including reperfusion but no effect on tobacco cessation counseling. There were no unexpected adverse events reported. Conclusions and Relevance: Among patients with acute myocardial infarction in Kerala, India, use of a quality improvement intervention compared with usual care did not decrease a composite of 30-day major adverse cardiovascular events. Further research is needed to understand the lack of efficacy. Trial Registration: clinicaltrials.gov Identifier: NCT02256657.

Acute coronary syndrome quality improvement in Kerala (ACS QUIK): Rationale and design for a cluster-randomized stepped-wedge trial.

Ischemic heart disease is the leading cause of death in India, and there are likely more myocardial infarctions in India than in any other country in the world. We have previously reported heterogeneous care for patients with myocardial infarction in Kerala, a state in southern India, including both gaps in optimal care and inappropriate care. Based on that prior work, limitations from previous nonrandomized quality improvement studies and promising gains in process of care measures demonstrated from previous randomized trials, we and the Cardiological Society of India-Kerala chapter sought to develop, implement, and evaluate a quality improvement intervention to improve process of care measures and clinical outcomes for these patients. In this article, we report the rationale and study design for the ACS QUIK cluster-randomized stepped-wedge clinical trial (NCT02256657) in which we aim to enroll 15,750 participants with acute coronary syndromes across 63 hospitals. To date, most participants are men (76%) and have ST-segment elevation myocardial infarction (63%). The primary outcome is 30-day major adverse cardiovascular events defined as death, recurrent infarction, stroke, or major bleeding. Our secondary outcomes include health-related quality of life and individual- and household-level costs. We also describe the principal features and limitations of the stepped-wedge study design, which may be important for other investigators or sponsors considering cluster-randomized stepped-wedge trials.

Genetic loci associated with ideal cardiovascular health: A meta-analysis of genome-wide association studies.

BACKGROUND: Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CV disease morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study on the trait. METHODS AND RESULTS: We examined 2 dichotomous phenotypes of ideal CV health-clinical (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80, not diabetic) and clinical+behavioral (clinical plus: not a current smoker, body mass index <25 kg/m(2))-among white participants aged 50±5 years. We performed a meta-analysis of 4 genome-wide association studies (total n=11,708) from the MESA, CARDIA, ARIC, and Framingham Heart Study cohorts. We identified a single-nucleotide polymorphism (rs445925) in the APOC1/APOE region that was associated with clinical ideal CV health at genome-wide level of significance (P<2.0 × 10(-9)). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for low-density lipoprotein cholesterol. CONCLUSION: A common single-nucleotide polymorphism in the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower CV risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.

Mosaic composition of ribA and wspB genes flanking the virB8-D4 operon in the Wolbachia supergroup B-strain, wStr.

The obligate intracellular bacterium, Wolbachia pipientis (Rickettsiales), is a widespread, vertically transmitted endosymbiont of filarial nematodes and arthropods. In insects, Wolbachia modifies reproduction, and in mosquitoes, infection interferes with replication of arboviruses, bacteria and plasmodia. Development of Wolbachia as a tool to control pest insects will be facilitated by an understanding of molecular events that underlie genetic exchange between Wolbachia strains. Here, we used nucleotide sequence, transcriptional and proteomic analyses to evaluate expression levels and establish the mosaic nature of genes flanking the T4SS virB8-D4 operon from wStr, a supergroup B-strain from a planthopper (Hemiptera) that maintains a robust, persistent infection in an Aedes albopictus mosquito cell line. Based on protein abundance, ribA, which contains promoter elements at the 5'-end of the operon, is weakly expressed. The 3'-end of the operon encodes an intact wspB, which encodes an outer membrane protein and is co-transcribed with the vir genes. WspB and vir proteins are expressed at similar, above average abundance levels. In wStr, both ribA and wspB are mosaics of conserved sequence motifs from Wolbachia supergroup A- and B-strains, and wspB is nearly identical to its homolog from wCobU4-2, an A-strain from weevils (Coleoptera). We describe conserved repeated sequence elements that map within or near pseudogene lesions and transitions between A- and B-strain motifs. These studies contribute to ongoing efforts to explore interactions between Wolbachia and its host cell in an in vitro system.

Performance of an electronic health record-based phenotype algorithm to identify community associated methicillin-resistant Staphylococcus aureus cases and controls for genetic association studies.

BACKGROUND: Community associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is one of the most common causes of skin and soft tissue infections in the United States, and a variety of genetic host factors are suspected to be risk factors for recurrent infection. Based on the CDC definition, we have developed and validated an electronic health record (EHR) based CA-MRSA phenotype algorithm utilizing both structured and unstructured data. METHODS: The algorithm was validated at three eMERGE consortium sites, and positive predictive value, negative predictive value and sensitivity, were calculated. The algorithm was then run and data collected across seven total sites. The resulting data was used in GWAS analysis. RESULTS: Across seven sites, the CA-MRSA phenotype algorithm identified a total of 349 cases and 7761 controls among the genotyped European and African American biobank populations. PPV ranged from 68 to 100% for cases and 96 to 100% for controls; sensitivity ranged from 94 to 100% for cases and 75 to 100% for controls. Frequency of cases in the populations varied widely by site. There were no plausible GWAS-significant (p < 5 E -8) findings. CONCLUSIONS: Differences in EHR data representation and screening patterns across sites may have affected identification of cases and controls and accounted for varying frequencies across sites. Future work identifying these patterns is necessary.

Factors Associated With Long-Term Weight Loss Following Bariatric Surgery Using 2 Methods for Repeated Measures Analysis.

We used electronic health record data from 162 patients enrolled in the NUgene Project (2002-2013) to determine demographic factors associated with long-term (from 1 to up to 9.5 (mean = 5.6) years) weight loss following Roux-en-Y gastric bypass surgery. Ninety-nine (61.1%) patients self-reported white, and 63 (38.9%) self-reported black, mixed, or missing race. The average percent weight loss was -33.4% (standard deviation, 9.3) at 1 year after surgery and -30.7% (standard deviation, 12.5) at the last follow-up point. We used linear mixed and semiparametric trajectory models to test the association of surgical and demographic factors (height, surgery age, surgery weight, surgery body mass index, marital status, sex, educational level, site, International Classification of Diseases code, Current Procedural Terminology code, Hispanic ethnicity, and self-reported race) with long-term percent weight loss and pattern of weight loss. We found that black, mixed, and missing races (combined) in comparison with white race were associated with a decreased percent weight loss of -4.31% (95% confidence interval: -7.30, -1.32) and were less likely to have higher and sustained percent weight loss (P = 0.04). We also found that less obese patients were less likely to have higher and sustained percent weight loss (P = 0.01). These findings may be helpful to patients in setting expectations after weight loss surgery.

Proteomic profiling of a robust Wolbachia infection in an Aedes albopictus mosquito cell line.

Wolbachia pipientis, a widespread vertically transmitted intracellular bacterium, provides a tool for insect control through manipulation of host-microbe interactions. We report proteomic characterization of wStr, a Wolbachia strain associated with a strong cytoplasmic incompatibility phenotype in its native host, Laodelphax striatellus. In the Aedes albopictus C/wStr1 mosquito cell line, wStr maintains a robust, persistent infection. MS/MS analyses of gel bands revealed a protein 'footprint' dominated by Wolbachia-encoded chaperones, stress response and cell membrane proteins, including the surface antigen WspA, a peptidoglycan-associated lipoprotein and a 73 kDa outer membrane protein. Functional classifications and estimated abundance levels of 790 identified proteins suggested that expression, stabilization and secretion of proteins predominate over bacterial genome replication and cell division. High relative abundances of cysteine desulphurase, serine/glycine hydroxymethyl transferase, and components of the α-ketoglutarate dehydrogenase complex in conjunction with above average abundances of glutamate dehydrogenase and proline utilization protein A support Wolbachia genome-based predictions for amino acid metabolism as a primary energy source. wStr expresses 15 Vir proteins of a Type IV secretion system and its transcriptional regulator. Proteomic characterization of a robust insect-associated Wolbachia strain provides baseline information that will inform further development of in vitro protocols for Wolbachia manipulation.

The risk vs. benefit calculus of anticoagulation in patients with ibrutinib-related atrial fibrillation.

For ibrutinib-related atrial fibrillation (IRAF), guidelines for anticoagulation do not exist. We sought to describe stroke, bleeding, and anticoagulation rates among patients with IRAF. We performed a single-center retrospective review of 168 patients treated with ibrutinib followed from 2013 to 2022. Over a median follow-up of 6.4 years, 44 (26.0%) patients developed IRAF of which 38 (86.4%) had a CHA2DS2-VASc ≥2 and 7 (15.9%) had a HAS-BLED ≥3. Anticoagulation was initiated in 20 (45.5%) without a clear pattern in scores, risk factors, or cumulative dose, besides having another reason for anticoagulation. Few patients with IRAF developed non-hemorrhagic CVA (n = 3, 6.8%) or significant bleeding (n = 3, 6.8%). Among those with each adverse outcome, 2 in each group were anticoagulated and all were older than 65 years old. In conclusion, decisions for anticoagulation vary widely and patients who are elderly or with HTN may be most at risk for CVA or significant bleed.

Anticoagulation Bridging in Patients With Left Ventricular Assist Device: A Regional Analysis of HeartMate 3 Recipients.

Advances in left ventricular assist device technologies have led to an improvement in pump hemocompatibility and outcomes. Because of concerns of thromboembolic complications in prior generations of left ventricular assist devices, bridging with parenteral anticoagulants was routinely. Management strategies of subtherapeutic INRs and their effects on the current generation of devices deserve review. We performed analysis of the MOMENTUM 3 trial including 6 centers in the mid-America region. Patients with subtherapeutic INRs (INR < 2) occurring after the index admission underwent chart review to determine the management strategies taken by clinicians. Strategies were divided into two groups, bridging or nonbridging. Of the 225 patients included in the analysis, 130 (58%) patients had a total of 235 subtherapeutic international normalized ratio (INR) events. Most (n = 179, 76.2%) of these INRs were not bridged (n = 100 warfarin dose adjustment, n = 79 no change in warfarin dose). Among those INRs (n = 56, 23.8%) treated with bridging, approximately half (n = 30, 53.6%) were treated with subcutaneous agents and other half (n = 26, 46.4%) were treated with intravenous agents. There was no difference in individual outcomes or composite endpoints of death, rehospitalization, CVA, or bleeding events between the groups.

Association of Patient Reported Outcomes With Caregiver Burden in Older Patients With Advanced Heart Failure: Insights From the SUSTAIN-IT Study.

BACKGROUND: Caregivers of patients with advanced heart failure may experience burden in providing care, but whether changes in patient health status are associated with caregiver burden is unknown. METHODS: This observational study included older patients (60-80 years old) receiving advanced surgical heart failure therapies and their caregivers at 13 US sites. Patient health status was assessed using the 12-item Kansas City Cardiomyopathy Questionnaire (range, 0-100; higher scores are better). Caregiver burden was assessed using the Oberst Caregiving Burden Scale, which measures time on task (OCBS-time) and task difficulty (OCBS-difficulty; range, 1-5; lower scores are better). Measurements occurred before surgery and 12 months after in 3 advanced heart failure cohorts: patients receiving long-term left ventricular assist device support; heart transplantation with pretransplant left ventricular assist device support; and heart transplantation without pretransplant left ventricular assist device support. Multivariable linear regression was used to identify predictors of change in OCBS-time and OCBS-difficulty at 12 months. RESULTS: Of 162 caregivers, the mean age was 61.0±9.4 years, 139 (86%) were female, and 140 (86%) were the patient's spouse. At 12 months, 99 (61.1%) caregivers experienced improved OCBS-time, and 61 (37.7%) experienced improved OCBS-difficulty (versus no change or worse OCBS). A 10-point higher baseline 12-item Kansas City Cardiomyopathy Questionnaire predicted lower 12-month OCBS-time (ß=-0.09 [95% CI, -0.14 to -0.03]; P<0.001) and OCBS-difficulty (ß=-0.08 [95% CI, -0.12 to -0.05]; P<0.001). Each 10-point improvement in the 12-item Kansas City Cardiomyopathy Questionnaire predicted lower 12-month OCBS-time (ß=-0.07 [95% CI, -0.12 to -0.03]; P=0.002) and OCBS-difficulty (ß=-0.09 [95% CI, -0.12 to -0.06]; P<0.001). CONCLUSIONS: Among survivors at 12 months, baseline and change in patient health status were associated with subsequent caregiver time on task and task difficulty in dyads receiving advanced heart failure surgical therapies, highlighting the potential for serial 12-item Kansas City Cardiomyopathy Questionnaire assessments to identify caregivers at risk of increased burden. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT02568930.

Race, substance use, and evaluation for heart transplantation: Insights from a large urban medical center.

It is unknown whether racial disparities in access to heart transplantation (HT) are amplified when coupled with substance use. We examined patients evaluated for HT over 8 years at an urban transplant center. We evaluated substance use and race/ethnicity as independent and interactive predictors of HT and left ventricular assist device (LVAD) implantation. Of 1,148 patients evaluated for HT, substance use was cited as an ineligibility factor in 151 (13%) patients, 16 (11%) of whom ultimately received HT. Significantly more non-Hispanic Black (NHB) patients were deemed ineligible due to substance use (n = 59, 19%) compared to other races/ethnicities (non-Hispanic white: n = 68, 12%; other race/ethnicity: n = 24, p = 0.002). No racial differences were observed in the likelihood of HT among patients initially excluded for substances, but more NHB patients ultimately received LVAD than the other racial groups. This study encourages greater awareness of the role of substance use and race in the HT evaluation.