Impact of Non-Alcoholic Fatty Liver Disease on Sepsis Inpatient Outcomes: A Nationwide Sample Analysis (2000-2019).

Background/Objectives: Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) are reported to have an increased risk of developing severe infections, leading to hospitalizations with sepsis. However, data regarding the impact of comorbid NAFLD on in-hospital outcomes of patients with sepsis is scarce. Methods: This nationwide retrospective observational study using discharge data from the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), and Agency for Healthcare Research and Quality included 21,057,911 adult patients who were admitted to hospitals in the United States between 2000 and 2019 with a primary discharge diagnosis of sepsis. These patients were categorized according to the presence or absence of comorbid NAFLD. The twenty-year trend of nationwide NAFLD prevalence among sepsis inpatients was elucidated. Multivariable logistic regression analysis was used to analyze NAFLD's impact on sepsis outcomes. Results: In the twenty-year study period, the prevalence of NALFD among sepsis inpatients trended up from 1.2% in 2000 to 4.2% in 2019. Similar trends were observed in regional analysis. While overall sepsis mortality decreased, comorbid NAFLD in sepsis patients was consistently associated with a higher adjusted in-hospital all-cause mortality rate (adjusted odds ratio (OR), 1.19; 95% confidence interval (CI), 1.07-1.32), higher odds of developing septic shock, and higher likelihood of development of multi-organ dysfunction. Conclusions: Comorbid NAFLD in the stage of NASH or cirrhosis is associated with higher in-hospital all-cause mortality and worse clinical outcomes in sepsis inpatients. Addressing this rising epidemic will be of paramount importance to improve sepsis in-hospital outcomes.

Digoxin Discontinuation in Patients with HFrEF on Beta-Blockers: Implication for Future "Knock-Out Trials" in Heart Failure.

BACKGROUND: National heart failure guidelines recommend quadruple therapy with renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors for patients with heart failure with reduced ejection fraction (HFrEF), most of whom also receive loop diuretics. However, the guidelines are less clear about the safe approaches to discontinuing older drugs whose decreasing or residual benefit is less well understood. The objective of this study was to examine whether digoxin can be safely discontinued in patients with HFrEF receiving beta-blockers. METHODS: In OPTIMIZE-HF, of 2,477 patients with HFrEF (EF ≤45%) receiving beta-blockers and digoxin, digoxin was discontinued in 450 patients. We assembled a propensity score-matched cohort of 433 pairs of patients in which digoxin continuation vs. discontinuation groups were balanced on 51 baseline characteristics. Using the same approach, from 992 patients not on beta-blockers, we assembled a matched cohort of 198 pairs of patients also balanced on 51 baseline characteristics. Hazard ratios (HRs) and 95% CIs for one-year outcomes were estimated. RESULTS: Among patients receiving beta-blockers, digoxin discontinuation had no association with the combined endpoint of heart failure readmission or death (HR, 1.01; 95% CI, 0.85-1.19), heart failure readmission (HR, 1.03; 95% CI, 0.85-1.25) or death (HR, 0.91; 95% CI, 0.72-1.14). Respective HRs (95% CIs) among patients not receiving beta-blockers were 1.60 (1.25-2.04), 1.62 (1.18-2.22) and 1.43 (1.08-1.89). CONCLUSIONS: Digoxin can be discontinued without increasing the risk of adverse outcomes in patients with HFrEF receiving beta-blockers. Future studies need to examine the residual benefit of older heart failure drugs to ensure their safe discontinuation in patients with HFrEF receiving newer guideline-directed medical therapy.

Heart Failure Among Asian American Subpopulations.

Importance: Heart failure (HF) is a leading cause of death in the US. The current evidence on the burdens of HF in Asian American populations, especially Asian American subgroups, is limited and inconsistent. Objective: To assess and compare the incidence and prevalence of HF in Asian American subgroups. Design, Setting, and Participants: This retrospective cohort study used electronic health record data from patients 40 years or older with health care encounters from January 1, 2015, to December 31, 2019, recorded in the Oracle Electronic Health Record Real-World Data database, which has more than 100 health care systems across the US contributing to the database as of February 2024. For prevalence analysis, the study samples were those who had at least 1 encounter in the study calendar year. For incidence analysis, participants were additionally limited to those without HF before the study year who also had encounter(s) the year before the study year. Data analysis was performed from August 1, 2023, to July 31, 2024. Exposure: Race and ethnicity were determined using patient self-reported data, which were categorized as Black, East Asian, South Asian, Southeast Asian, other Asian (without specified ethnicity), and White. Main Outcomes and Measures: Outcomes were incidence and prevalence of HF, identified using recorded International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes. Age- and sex-standardized incidence and prevalence were used to calculate the risk ratio of each racial and ethnic group compared with White patients. Results: Incidence and prevalence analyses were performed for 6 845 791 patients (mean [SD] age, 62.1 [12.5] years; 59.9% female; 2.8% Asian, 6.7% Black, and 90.5% White) and for 13 440 234 patients (mean [SD] age, 61.7 [12.7] years; 57.0% female; 2.9% Asian, 7.1% Black, and 90.0% White), respectively. Using the 2015 population as the standard, age- and sex-standardized HF incidence was 2.26% (95% CI, 2.07%-2.45%) for Southeast Asian patients, 1.56% (95% CI, 1.31%-1.82%) for South Asian patients, and 1.22% (95% CI, 1.06%-1.38%) for East Asian patients compared with 1.58% (95% CI, 1.57%-1.59%) for White patients and 2.39% (95% CI, 2.36%-2.42%) for Black patients. Similarly, heterogeneous rates in Asian American subgroups were also observed in the prevalence analysis. Conclusions and Relevance: In this study of HF outcomes, the disparities between Southeast and East Asian patients were larger than those between Black and White patients, with the estimates in Southeast Asian patients being similar to those of Black patients. These findings reinforce that individual Asian ethnicities and cardiovascular risk factors should be considered in the assessment of HF risks.

Skilled Nursing Facility Rehabilitation Intensity and Successful Discharge in Persons with Dementia.

OBJECTIVES: Skilled therapies (STs), including audiology, speech-language therapy, occupational therapy, and physical therapy, can address functional deficits in dementia. This study aims to quantify the association between ST and successful discharge after heart failure (HF) hospitalization in persons living with dementia. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: We included veterans with dementia (VwD) hospitalized for HF in Veterans Affairs (VA) medical centers and then admitted to non-VA skilled nursing facilities (SNFs) from January 2011 to June 2019. METHODS: Follow-up continued 120 days after SNF admission. We measured ST hours per week using MDS admission assessments. We defined successful discharge as SNF discharge occurring within 90 days of SNF admission with MDS discharge status not hospital or institutional setting, and 30 days' survival after discharge without Medicare or VA-paid rehospitalization or reinstitutionalization. We estimated relative risk using multiple variable regression to adjust for measured sources of confounding. RESULTS: Our final sample included 8255 VwD. The mean (SD) age was 80 (10) years, and 8074 (98%) were male. Successful discharge occurred in 2776 (34%) of the sample. The median (IQR) weekly hours of ST was 10.4 (7.1-12.1). Sextile 1 received less than 5.2 hours per week of ST. The adjusted relative risk (95% CI) for sextiles 2-6 compared with sextile 1 were, respectively, 2.20 (1.85-2.62), 2.48 (2.09-2.94), 2.52 (2.12-2.99), 2.62 (2.21-3.11), and 2.69 (2.27-3.19). DISCUSSION: During SNF care after HF hospitalization, 5.3 or more hours of STs per week was associated with a higher rate of successful discharge, in a roughly dose-dependent fashion, up to a 170% increase in the highest sextile of ST hours. CONCLUSIONS AND IMPLICATIONS: Higher ST hours are associated with successful discharge from SNF after HF hospitalization.

Effect of Masking Secondary to the COVID-19 Pandemic on Functional Capacity Improvement in Cardiac Rehabilitation.

PURPOSE: Given the difficulty to perform exercise training wearing a mask, we examined differences in functional capacity improvement between masking during the coronavirus disease 2019 (COVID-19) pandemic and non-masking prior to the pandemic for patients undergoing cardiac rehabilitation (CR). METHODS: Records of 660 patients who underwent and completed ≥ 18 sessions of CR in 2018 (n = 318, non-masking) and in 2022 (n = 342, masking) at an academic health system were analyzed. The primary outcome was post-CR change in functional capacity in metabolic equivalents (MET) measured by exercise stress test. Sessions of CR participation and changes in depression, anxiety, and quality of life scores were secondary outcomes. We used multivariable linear regression to adjust for differences in baseline CR outcome measures, demographics, American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) risk, and comorbid conditions. RESULTS: Baseline age (64.6 ± 0.46 yr), sex (28% female), and racial distribution (85% white) were similar between the masking and non-masking groups. Non-masking patients were more likely to be classified in the AACVPR high risk category and had lower anxiety scores at baseline compared to masking patients. After CR, both groups had similar and significant improvements in depression, anxiety, and quality of life scores, but the improvement in functional capacity was lower in the masking group (-0.62 ± 0.12 MET, P < .001) compared to the non-masking group. Results remained significant after multivariable adjustment. CONCLUSIONS: Cardiac rehabilitation patients requiring masking during the COVID-19 pandemic had less improvement in functional capacity than patients who did not wear masks during CR prior to the pandemic. Interventions to mitigate the potential side effects of masking for CR patients may require further exploration.

Concurrent Care and Use of Advanced Cardiac Therapies for Hospitalized Veterans With Heart Failure.

CONTEXT: Concurrent care allows patients to receive hospice while continuing disease-directed therapies. This treatment model is available in the Veterans Administration (VA) medical system, but its use in Veterans with heart failure (HF) is unexplored. OBJECTIVE: To compare use of advanced HF therapies 30 days posthospitalization in Veterans on hospice versus not on hospice following admission for HF exacerbation. METHODS: We evaluated Veterans admitted for HF exacerbation to VA hospitals between Jan 2011 and June 2019 who received advanced HF therapies, hospice services, or both postdischarge. Concurrent care was defined as receiving both hospice services and advanced HF therapies. Demographics, comorbidities, and prior healthcare utilization were compared. Secondary outcomes included burdensome transitions and mortality. RESULTS: Among 317,967 HF Veterans, 18,350 (5.8%) chose hospice posthospitalization. Only 58 hospice-enrolled Veterans (0.3%) received advanced HF therapies (i.e. concurrent care) within 30 days postdischarge. Of 299,617 Veterans not on hospice, 6,083 (2.0%) received advanced HF therapies (0.3% vs. 2.0%; P < 0.001). Veterans receiving concurrent care had higher six-month mortality than those receiving advanced HF therapies alone (77.6% vs. 14.9%, SMD 1.61). Hazard of burdensome transitions was similar (adjusted HR 1.44, 95% CI 0.95-2.17). CONCLUSION: Veterans with HF receiving concurrent care were few and experienced higher mortality. Rate of burdensome transitions was similar between Veterans receiving concurrent care and those not on hospice. Further research may explore why Veterans infrequently utilize concurrent care at the end of life.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry.

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

Variations in antihypertensive medication treatment and blood pressure control among Veterans with HIV and existing hypertension.

BACKGROUND: Hypertension is a leading risk factor for cardiovascular disease among patients living with HIV (PLWH). Understanding the predictors and patterns of antihypertensive medication prescription and blood pressure (BP) control among PLWH with hypertension (HTN) is important to improve the primary prevention efforts for this high-risk population. We sought to assess important patient-level correlates (eg, race) and inter-facility variations in antihypertension medication prescriptions and BP control among Veterans living with HIV (VLWH) and HTN. METHODS: We studied VLWH with a diagnosis of HTN who received care in the Veterans Health Administration (VHA) from January 2018 to December 2019. We evaluated HTN treatment and blood pressure control across demographic variables, including race, and by medical comorbidities. Data were also compared among VHA facilities. Predictors of HTN treatment and control were assessed in 2-level hierarchical multivariate logistic regression models to estimate odds ratios (ORs). The VHA facility random-effects parameters from the hierarchical models were used to calculate the median odds ratios to characterize the variation across the different VHA facilities. RESULTS: A total of 17,468 VLWH with HTN (mean age 61 years, 97% male, 54% Black, 40% White) who received care within the VHA facilities in 2018-2019 were included. 73% were prescribed antihypertension medications with higher prescription rates among Black vs White patients (75% vs 71%) and higher prescription rates among patients with a history of cardiovascular disease, diabetes, and kidney disease (>80%), and those receiving antiretroviral therapy and with controlled HIV viral load (∼75%). Only 27% of VLWH with HTN had optimal BP control of systolic BP <130 mmHg and diastolic BP <80 mmHg, with a lower rate of control among Black vs White patients (24% v. 31%). In multivariate regression, Black patients had a higher likelihood of HTN medication prescription (OR 1.32, 95% CI: 1.22-1.42) but were less likely to have optimal BP control (OR 0.82; 0.76-0.88). Important positive correlates of antihypertensive prescription and optimal BP control included: number of outpatient visits in prior year, and histories of diabetes, coronary artery disease, and heart failure. There was about 10% variability in both antihypertensive prescription and BP control patterns between VHA facilities for patients with similar characteristics. There was increased inter-facility variation in antihypertensive prescription among those with a history of heart failure and those not receiving antiretroviral therapy. CONCLUSION: In a retrospective analysis of large VHA data, we found that VLWH with HTN have suboptimal antihypertensive medication prescription and BP control. Black VLWH had higher HTN medication prescription rates but lower optimal BP control.

Geographic access to cardiac rehabilitation and cardiovascular disease outcomes: A study of rural United States counties.

Prior studies have examined rural-urban disparities in access to cardiac rehabilitation (CR). However, few have examined the relationship between disparate access to CR and cardiovascular disease outcomes in rural areas. In this analysis of 1975 nonmetro United States counties, we investigated the relationship between number of hospitals with CR and Medicare-population hospitalization rates (per 1000 adults ≥65 years) and county-population mortality rates (per 100,000 adults ≥18 years) due to coronary heart disease (CHD), heart failure (HF), or stroke, using multivariable linear-regression-modeling adjusting for socio-demographic and comorbid conditions. Median CHD hospitalization (13.0 vs. 12.2), HF hospitalization (16.1 vs. 13.3), HF death (114.2 vs. 110.9), stroke hospitalization (12.0 vs. 10.9), and stroke death (39.6 vs. 37.1) rates were higher in nonmetro counties without versus with a CR facility (p-values< 0.001). There were inverse correlations between number of hospitals with CR and CHD (r= -0.161), HF (r= -0.261) and stroke (r= -0.237) hospitalization rates, and stroke mortality (r= -0.144) rates (p-values< 0.001). After adjustment, as the number of hospitals with CR increased, there were decreases in hospitalization rates of 1.78 for CHD, 7.20 for HF, and 2.43 for stroke, per 1000 in the population (p-values < 0.001) and decreases in stroke deaths of 9.17 per 100,000 in the population (p= 0.02). Access to hospitals with CR in US nonmetro counties is inversely related to CHD, HF, and stroke hospitalization, and stroke mortality. Our findings call for reducing barriers to CR in nonmetro communities and further exploring the relationship between CR and stroke outcomes.

Time to Dementia Diagnosis Among Veterans with Comorbid Insomnia and Depressive Episodes.

Background: Older adults with heart failure are at elevated risk of Alzheimer's disease and related dementias (AD/ADRD). Research suggests that insomnia and depressive episodes contribute somewhat dissociable impacts on risk for AD/ADRD in this patient population, although the temporal ordering of effects is unknown. Objective: This study examined time to dementia diagnosis among patients with comorbid insomnia and/or depressive episodes in an epidemiological sample. Methods: Secondary data analyses were conducted using a cohort study of 203,819 Veterans with a primary admission diagnosis of heart failure in 129 VA Medical Centers. Results: Patients with diagnoses of both insomnia and depressive episodes had the shortest time to a dementia diagnosis at both 1-year (Hazard ratio = 1.43, 95% CI [1.36, 1.51]) and 3-year follow-up time points (Hazard ratio = 1.40, 95% CI [1.34, 1.47]) versus patients with one or neither comorbidity. Conclusions: Individuals with both comorbidities had the shortest time to dementia onset. Screening for these comorbidities may help to identify patients at elevated risk of dementia who could benefit from enhanced monitoring or early intervention strategies for more rapid detection and management of dementia symptoms.

Shared Medical Appointments in Heart Failure for Post Acute Care Follow-Up: A Randomized Controlled Trial.

BACKGROUND: Shared medical appointments (SMAs) in heart failure (HF) are medical visits where several patients with HF meet with multidisciplinary providers at the same time for efficient and comprehensive care. It is unknown whether HF-SMAs can improve overall and cardiac health status for high-risk patients with HF discharged from acute care. METHODS AND RESULTS: A 3-site, open-label, randomized-controlled-trial was conducted. Participants within 12 weeks of HF acute care (emergency-room/hospitalization) requiring intravenous diuretic therapy were randomized to receive either HF-SMA or usual HF clinical care (usual-care) on a 1:1 ratio. The HF-SMA team, which consisted of a nurse, nutritionist, psychologist, nurse practitioner and/or a clinical pharmacist, provided four 2-hour session HF-SMAs that met every other week for 8 weeks. Primary outcomes were the overall health status measured by European Quality of Life Visual Analog Scale and cardiac health status by Kansas City Cardiomyopathy Questionnaire, 180 days postrandomization. Of the 242 patients enrolled (HF-SMA n=117, usual-care n=125, mean age 69.3±9.4 years, 71.5% White patients, 94.6% male), 84% of participants completed the study (n=8 HF-SMA and n=9 usual-care patients died). After 180 days, both HF-SMA and usual-care participants had significant improvements from baseline in Kansas City Cardiomyopathy Questionnaire that were not statistically different. Only HF-SMA participants had significant improvements in European Quality of Life Visual Analog Scale (mean change = 7.2±15.8 in HF-SMA versus -0.4±19.0 points in usual-care, P < 0.001). CONCLUSIONS: Both HF-SMA and usual-care in participants with HF achieved significant improvements in cardiac health status, but only a team approach through HF-SMA achieved significant improvements in overall health status. Future larger studies are needed to evaluate hospitalization and death outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02481921.

Artificial intelligence approaches for phenotyping heart failure in U.S. Veterans Health Administration electronic health record.

AIMS: Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD-code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients. METHODS AND RESULTS: The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP-HF) and non-HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF-related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP-HF as cases (PPV, 0.86; sensitivity, 0.86). From the 'HF ICD-code universe', we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54). CONCLUSIONS: These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.

Identification and outcomes of KDIGO-defined chronic kidney disease in 1.4 million U.S. Veterans with heart failure.

AIMS: According to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline, the definition of chronic kidney disease (CKD) requires the presence of abnormal kidney structure or function for >3 months with implications for health. CKD in patients with heart failure (HF) has not been defined using this definition, and less is known about the true health implications of CKD in these patients. The objective of the current study was to identify patients with HF who met KDIGO criteria for CKD and examine their outcomes. METHODS AND RESULTS: Of the 1 419 729 Veterans with HF not receiving kidney replacement therapy, 828 744 had data on ≥2 ambulatory serum creatinine >90 days apart. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (n = 185 821) or urinary albumin-to-creatinine ratio (uACR) >30 mg/g (n = 32 730) present twice >3 months apart. Normal kidney function (NKF) was defined as eGFR ≥60 ml/min/1.73 m2, present for >3 months, without any uACR >30 mg/g (n = 365 963). Patients with eGFR <60 ml/min/1.73 m2 were categorized into four stages: 45-59 (n = 72 606), 30-44 (n = 74 812), 15-29 (n = 32 077), and <15 (n = 6326) ml/min/1.73 m2. Five-year all-cause mortality occurred in 40.4%, 57.8%, 65.6%, 73.3%, 69.7%, and 47.5% of patients with NKF, four eGFR stages, and uACR >30mg/g (albuminuria), respectively. Compared with NKF, hazard ratios (HR) (95% confidence intervals [CI]) for all-cause mortality associated with the four eGFR stages and albuminuria were 1.63 (1.62-1.65), 2.00 (1.98-2.02), 2.49 (2.45-2.52), 2.28 (2.21-2.35), and 1.22 (1.20-1.24), respectively. Respective age-adjusted HRs (95% CIs) were 1.13 (1.12-1.14), 1.36 (1.34-1.37), 1.87 (1.84-1.89), 2.24 (2.18-2.31) and 1.19 (1.17-1.21), and multivariable-adjusted HRs (95% CIs) were 1.11 (1.10-1.12), 1.24 (1.22-1.25), 1.46 (1.43-1.48), 1.42 (1.38-1.47), and 1.13 (1.11-1.16). Similar patterns were observed for associations with hospitalizations. CONCLUSION: Data needed to define CKD using KDIGO criteria were available in six out of ten patients, and CKD could be defined in seven out of ten patients with data. HF patients with KDIGO-defined CKD had higher risks for poor outcomes, most of which was not explained by abnormal kidney structure or function. Future studies need to examine whether CKD defined using a single eGFR is characteristically and prognostically different from CKD defined using KDIGO criteria.

Clinical Outcomes After Acute Coronary Syndromes or Revascularization Among People Living With HIV: A Systematic Review and Meta-Analysis.

Importance: Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately. Objective: To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group. Data Sources: Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023. Study Selection: Included studies met the following criteria: patients living with HIV and HIV-negative comparator group included, patients presenting with ACS or undergoing PCI included, and longitudinal follow-up data collected after the initial event. Data Extraction and Synthesis: Data extraction was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Clinical outcome data were pooled using a random-effects model meta-analysis. Main Outcome and Measures: The following clinical outcomes were studied: all-cause mortality, major adverse cardiovascular events, cardiovascular death, recurrent ACS, stroke, new heart failure, total lesion revascularization, and total vessel revascularization. The maximally adjusted relative risk (RR) of clinical outcomes on follow-up comparing patients living with HIV with patients in control groups was taken as the main outcome measure. Results: A total of 15 studies including 9499 patients living with HIV (pooled proportion [range], 76.4% [64.3%-100%] male; pooled mean [range] age, 56.2 [47.0-63.0] years) and 1 531 117 patients without HIV in a control group (pooled proportion [range], 61.7% [59.7%-100%] male; pooled mean [range] age, 67.7 [42.0-69.4] years) were included; both populations were predominantly male, but patients living with HIV were younger by approximately 11 years. Patients living with HIV were also significantly more likely to be current smokers (pooled proportion [range], 59.1% [24.0%-75.0%] smokers vs 42.8% [26.0%-64.1%] smokers) and engage in illicit drug use (pooled proportion [range], 31.2% [2.0%-33.7%] drug use vs 6.8% [0%-11.5%] drug use) and had higher triglyceride (pooled mean [range], 233 [167-268] vs 171 [148-220] mg/dL) and lower high-density lipoprotein-cholesterol (pooled mean [range], 40 [26-43] vs 46 [29-46] mg/dL) levels. Populations with and without HIV were followed up for a pooled mean (range) of 16.2 (3.0-60.8) months and 11.9 (3.0-60.8) months, respectively. On postdischarge follow-up, patients living with HIV had lower prevalence of statin (pooled proportion [range], 53.3% [45.8%-96.1%] vs 59.9% [58.4%-99.0%]) and ß-blocker (pooled proportion [range], 54.0% [51.3%-90.0%] vs 60.6% [59.6%-93.6%]) prescriptions compared with those in the control group, but these differences were not statistically significant. There was a significantly increased risk among patients living with HIV vs those without HIV for all-cause mortality (RR, 1.64; 95% CI, 1.32-2.04), major adverse cardiovascular events (RR, 1.11; 95% CI, 1.01-1.22), recurrent ACS (RR, 1.83; 95% CI, 1.12-2.97), and admissions for new heart failure (RR, 3.39; 95% CI, 1.73-6.62). Conclusions and Relevance: These findings suggest the need for attention toward secondary prevention strategies to address poor outcomes of cardiovascular disease among patients living with HIV.

Rare genetic variation in VE-PTP is associated with central serous chorioretinopathy, venous dysfunction and glaucoma.

Central serous chorioretinopathy (CSC) is a fluid maculopathy whose etiology is not well understood. Abnormal choroidal veins in CSC patients have been shown to have similarities with varicose veins. To identify potential mechanisms, we analyzed genotype data from 1,477 CSC patients and 455,449 controls in FinnGen. We identified an association for a low-frequency (AF=0.5%) missense variant (rs113791087) in the gene encoding vascular endothelial protein tyrosine phosphatase (VE-PTP) (OR=2.85, P=4.5×10-9). This was confirmed in a meta-analysis of 2,452 CSC patients and 865,767 controls from 4 studies (OR=3.06, P=7.4×10-15). Rs113791087 was associated with a 56% higher prevalence of retinal abnormalities (35.3% vs 22.6%, P=8.0×10-4) in 708 UK Biobank participants and, surprisingly, with varicose veins (OR=1.31, P=2.3×10-11) and glaucoma (OR=0.82, P=6.9×10-9). Predicted loss-of-function variants in VEPTP, though rare in number, were associated with CSC in All of Us (OR=17.10, P=0.018). These findings highlight the significance of VE-PTP in diverse ocular and systemic vascular diseases.

Real-World Efficacy and Safety of Universal 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve Patients from a Nationwide HCV Registry in Taiwan.

INTRODUCTION: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). METHODS: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. RESULTS: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. CONCLUSION: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

A multi-ancestry GWAS of Fuchs corneal dystrophy highlights the contributions of laminins, collagen, and endothelial cell regulation.

Fuchs endothelial corneal dystrophy (FECD) is a leading indication for corneal transplantation, but its molecular etiology remains poorly understood. We performed genome-wide association studies (GWAS) of FECD in the Million Veteran Program followed by multi-ancestry meta-analysis with the previous largest FECD GWAS, for a total of 3970 cases and 333,794 controls. We confirm the previous four loci, and identify eight novel loci: SSBP3, THSD7A, LAMB1, PIDD1, RORA, HS3ST3B1, LAMA5, and COL18A1. We further confirm the TCF4 locus in GWAS for admixed African and Hispanic/Latino ancestries and show an enrichment of European-ancestry haplotypes at TCF4 in FECD cases. Among the novel associations are low frequency missense variants in laminin genes LAMA5 and LAMB1 which, together with previously reported LAMC1, form laminin-511 (LM511). AlphaFold 2 protein modeling, validated through homology, suggests that mutations at LAMA5 and LAMB1 may destabilize LM511 by altering inter-domain interactions or extracellular matrix binding. Finally, phenome-wide association scans and colocalization analyses suggest that the TCF4 CTG18.1 trinucleotide repeat expansion leads to dysregulation of ion transport in the corneal endothelium and has pleiotropic effects on renal function.