Regenerative engineering of long bones using the small molecule forskolin.

Bone grafting procedures have become increasingly common in the United States, with approximately 500,000 cases occurring each year at a societal cost exceeding $2.4 billion. Recombinant human bone morphogenetic proteins (rhBMPs) are therapeutic agents that have been widely used by orthopedic surgeons to stimulate bone tissue formation alone and when paired with biomaterials. However, significant limitations such as immunogenicity, high production cost, and ectopic bone growth from these therapies remain. Therefore, efforts have been made to discover and repurpose osteoinductive small-molecule therapeutics to promote bone regeneration. Previously, we have demonstrated that a single-dose treatment with the small-molecule forskolin for just 24 h induces osteogenic differentiation of rabbit bone marrow-derived stem cells in vitro, while mitigating adverse side effects attributed with prolonged small-molecule treatment schemes. In this study, we engineered a composite fibrin-PLGA [poly(lactide-co-glycolide)]-sintered microsphere scaffold for the localized, short-term delivery of the osteoinductive small molecule, forskolin. In vitro characterization studies showed that forskolin released out of the fibrin gel within the first 24 h and retained its bioactivity toward osteogenic differentiation of bone marrow-derived stem cells. The forskolin-loaded fibrin-PLGA scaffold was also able to guide bone formation in a 3-mo rabbit radial critical-sized defect model comparable to recombinant human bone morphogenetic protein-2 (rhBMP-2) treatment, as demonstrated through histological and mechanical evaluation, with minimal systemic off-target side effects. Together, these results demonstrate the successful application of an innovative small-molecule treatment approach within long bone critical-sized defects.

A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association.

A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.

Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association.

Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound impacts on morbidity and mortality. There are multisystem consequences of poor cardiovascular-kidney-metabolic health, with the most significant clinical impact being the high associated incidence of cardiovascular disease events and cardiovascular mortality. There is a high prevalence of poor cardiovascular-kidney-metabolic health in the population, with a disproportionate burden seen among those with adverse social determinants of health. However, there is also a growing number of therapeutic options that favorably affect metabolic risk factors, kidney function, or both that also have cardioprotective effects. To improve cardiovascular-kidney-metabolic health and related outcomes in the population, there is a critical need for (1) more clarity on the definition of cardiovascular-kidney-metabolic syndrome; (2) an approach to cardiovascular-kidney-metabolic staging that promotes prevention across the life course; (3) prediction algorithms that include the exposures and outcomes most relevant to cardiovascular-kidney-metabolic health; and (4) strategies for the prevention and management of cardiovascular disease in relation to cardiovascular-kidney-metabolic health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence. It is also critical to incorporate considerations of social determinants of health into care models for cardiovascular-kidney-metabolic syndrome and to reduce care fragmentation by facilitating approaches for patient-centered interdisciplinary care. This presidential advisory provides guidance on the definition, staging, prediction paradigms, and holistic approaches to care for patients with cardiovascular-kidney-metabolic syndrome and details a multicomponent vision for effectively and equitably enhancing cardiovascular-kidney-metabolic health in the population.

CEACAM6 as a Novel Therapeutic Target to Boost HO-1-mediated Antioxidant Defense in COPD.

Rationale: Tobacco smoking and air pollution are primary causes of chronic obstructive pulmonary disease (COPD). However, only a minority of smokers develop COPD. The mechanisms underlying the defense against nitrosative/oxidative stress in nonsusceptible smokers to COPD remain largely unresolved. Objectives: To investigate the defense mechanisms against nitrosative/oxidative stress that possibly prevent COPD development or progression. Methods: Four cohorts were investigated: 1) sputum samples (healthy, n = 4; COPD, n = 37), 2) lung tissue samples (healthy, n = 13; smokers without COPD, n = 10; smoker+COPD, n = 17), 3) pulmonary lobectomy tissue samples (no/mild emphysema, n = 6), and 4) blood samples (healthy, n = 6; COPD, n = 18). We screened 3-nitrotyrosine (3-NT) levels, as indication of nitrosative/oxidative stress, in human samples. We established a novel in vitro model of a cigarette smoke extract (CSE)-resistant cell line and studied 3-NT formation, antioxidant capacity, and transcriptomic profiles. Results were validated in lung tissue, isolated primary cells, and an ex vivo model using adeno-associated virus-mediated gene transduction and human precision-cut lung slices. Measurements and Main Results: 3-NT levels correlate with COPD severity of patients. In CSE-resistant cells, nitrosative/oxidative stress upon CSE treatment was attenuated, paralleled by profound upregulation of heme oxygenase-1 (HO-1). We identified carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as a negative regulator of HO-1-mediated nitrosative/oxidative stress defense in human alveolar type 2 epithelial cells (hAEC2s). Consistently, inhibition of HO-1 activity in hAEC2s increased the susceptibility toward CSE-induced damage. Epithelium-specific CEACAM6 overexpression increased nitrosative/oxidative stress and cell death in human precision-cut lung slices on CSE treatment. Conclusions: CEACAM6 expression determines the hAEC2 sensitivity to nitrosative/oxidative stress triggering emphysema development/progression in susceptible smokers.

Angiotensin Receptor Neprilysin Inhibitor Use and Blood Pressure Lowering in Patients With Heart Failure With Reduced Ejection Fraction Across the Spectrum of Kidney Function: An Analysis of the Veterans Administrative Health System.

BACKGROUND: A substantial proportion of patients with heart failure and kidney disease have poorly controlled blood pressures. This study aimed to evaluate patterns of blood pressure after initiation of an angiotensin receptor neprilysin inhibitor (ARNI) or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) across the spectrum of kidney function. METHODS: Between 2016 and 2020, we evaluated 26,091 patients admitted to a Veterans Affairs hospital for an acute heart failure exacerbation with reduced ejection fraction. We assessed patterns of systolic and diastolic blood pressure among those started on ARNI or ACEI/ARB over 6 months, overall and across estimated glomerular filtration rate (eGFR). To account for differential treatment factors, we applied 1:1 propensity score matching using 15 known baseline covariates. RESULTS: There were 13,781 individuals treated with an ACEI or ARB and 2589 individuals treated with an ARNI prescription. After propensity score matching, 839 patients were matched in each of the ARNI and ACEI/ARB groups. Mean baseline estimated glomerular filtration rate (eGFR) was 63.8 (standard deviation 21.6), and 10% had stage 4 or 5 chronic kidney disease. Patients in the ARNI group experienced greater systolic blood pressure reduction at month 3 (-5.2 mmHg vs -2.2 mmHg, ARNI vs ACEI/ARB; P < 0.001), and month 6 (-4.7 mmHg vs -1.85 mmHg, ARNI vs ACEI/ARB; P < 0.001). These differences in systolic blood pressure by 6 months did not vary by eGFR above and below 60 mL/min/1.73m2 or continuously across a wide range of eGFR (Pinteraction > 0.10 for both). CONCLUSION: The use of ARNI was associated with significant reduction in blood pressure as compared to the ACEI/ARB group overall and across the eGFR spectrum, including in advanced chronic kidney disease.

Proportional troponin changes and risk for outcomes with intervention strategies in non-ST-elevation acute coronary syndrome across kidney function.

AIMS: This analysis evaluates whether proportional serial cardiac troponin (cTn) change predicts benefit from an early versus delayed invasive, or conservative treatment strategies across kidney function in non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Patients diagnosed with NSTE-ACS in the Veterans Health Administration between 1999 and 2022 were categorized into terciles (<20%, 20 to ≤80%, >80%) of proportional change in serial cTn. Primary outcome included mortality or rehospitalization for myocardial infarction at 6 and 12 months, in survivors of index admission. Adjusted hazard ratio (HR) with 95% confidence Intervals (95% confidence interval [CI]) were calculated for the primary outcome for an early invasive (≤24 h of the index admission), delayed invasive (>24 h of index admission to 90-days postdischarge), or a conservative management. RESULTS: Chronic kidney disease (CKD) was more prevalent (45.3%) in the lowest versus 42.2% and 43% in middle and highest terciles, respectively (p < 0.001). Primary outcome is more likely for conservative versus early invasive strategy at 6 (HR: 1.44, 95% CI: 1.37-1.50) and 12 months (HR: 1.44, 95% CI: 1.39-1.50). A >80% proportional change demonstrated HR (95% CI): 0.90 (0.83-0.97) and 0.93 (0.88-1.00; p = 0.041) for primary outcome at 6 and 12 months, respectively, when an early versus delayed invasive strategy was used, across CKD stages. CONCLUSIONS: Overall, the invasive strategy was safe and associated with improved outcomes across kidney function in NSTE-ACS. Additionally, >80% proportional change in serial troponin in NSTE-ACS is associated with benefit from an early versus a delayed invasive strategy regardless of kidney function. These findings deserve confirmation in randomized controlled trials.

Non-steroidal mineralocorticoid receptor antagonists and cardiorenal outcomes in chronic kidney disease.

The burden of adverse cardiorenal outcomes among patients with the trifecta of diabetes, heart failure (HF) and chronic kidney disease (CKD) remains high. Steroidal mineralocorticoid receptor antagonists (MRAs) have been shown to improve clinical outcomes in patients with HF, however, there is significant underutilization of these agents, especially in patients with advanced CKD. Non-steroidal MRAs are an emerging therapeutic option for patients with diabetic kidney disease and are now guideline-supported in this population. Non-steroidal MRAs have a unique pharmacological profile distinct from their steroidal counterparts that retains the class-specific cardiorenal benefits but may help mitigate adverse effects, especially hyperkalaemia, in patients with CKD. In this review we summarize the current evidence on the use of non-steroidal MRAs for improving cardiorenal outcomes in patients with CKD and diabetes, as well as for combination use alongside other foundational medical therapies used in HF and CKD.

Adjunctive Dexmedetomidine in Alcohol Withdrawal Syndrome: A Systematic Review and Meta-analysis of Retrospective Cohort Studies and Randomized Controlled Trials.

OBJECTIVE: To investigate whether dexmedetomidine (DEX), as adjunctive therapy to benzodiazepine (BZD), is superior to BZD alone in critically ill patients with alcohol withdrawal syndrome (AWS). DATA SOURCES: PubMed Central, Cochrane CENTRAL, ClinicalTrials.gov and Google Scholar were used as search databases. Specific keywords and MeSH terms were "dexmedetomidine," "benzodiazepine," and "alcohol withdrawal syndrome." The last search was on September 16, 2022. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials (RCTs) and nonrandomized/cohort studies exploring the use of DEX in the management of AWS were included. A total of 12 studies were included in the systematic review and 7 in the meta-analysis. DATA SYNTHESIS: The intensive care unit length of stay (ICU LOS) was found to have a mean difference (MD) of 48.06 [37.48, 58.64], P = <0.001 for the cohort subgroup, significantly favoring the DEX arm, but, in contrast, pooled RCT data showed a result of -20.07 [-36.86, -3.28], P = 0.02, a shorter ICU LOS for the DEX arm. Bradycardia and hypotension incidence significantly favored the BZD arm in both subgroups. This study compares the effectiveness of adjunctive DEX in clinical practice and aims to help providers in critical decision-making by compiling and analyzing the best current available evidence of its use in AWS. CONCLUSIONS: Based on low to very low level of evidence, adjunctive DEX showed no significant difference for ICU LOS when compared with BZD alone. Pooled randomized trials potentially show a benefit but are similarly limited by their low quality of evidence.

Elderly people's preferences for healthcare facilities in Shanghai: gender features and influencing factor analysis.

BACKGROUND: China has one of the fastest paces of the growing aging population, High-level policymakers have recently recognized the aging population presents significant challenges to the Chinese healthcare system. In this context, the healthcare-seeking behaviors of the elderly population have become an essential field of study. It is necessary to understand their access to health services and to improve their quality of life, as well as to help policymakers to formulate healthcare policy. The study empirically investigates the factors influencing the elderly population's healthcare-seeking behaviors in Shanghai, China, especially in choosing the quality of healthcare facilities to visit. METHODS: We designed a cross-sectional study. The data of this study were derived from the "Shanghai elderly medical demand characteristics questionnaire" in the middle of November to early December 2017. A total of 625 individuals were included in the final sample. Logistic regression was adopted to investigate the differences in healthcare-seeking behaviors between elderly people when suffer from mild illness, severe illness and follow-up treatment. Next, the differences in gender were also discussed. RESULTS: Factors affecting the healthcare-seeking behaviors of the elderly differ in mild illness and severe illness situations. For mild illness, demographic factors (gender and age) and socioeconomic factors (income and employment) play an important role in elderly healthcare choices. Female and older elderlies are more likely to choose local, lower-quality facilities, whereas those with high income and private employment are more likely to choose higher-quality facilities. For severe illness, socioeconomic factors (income and employment) are important. Furthermore, individuals with basic medical insurance are more likely to choose lower-quality facilities. CONCLUSION: This study has shown that the affordability of public health services should be addressed. Medical policy support may be an important way to reduce the gap in access to medical services. We should pay attention to the gender differences in the elderly's choice of medical treatment behavior, consider the differences in the needs of male and female elderly. our findings are only for elderly Chinese participants in the greater Shanghai area.

Clinical characteristics and treatment of patients with central pulmonary embolism and right heart thrombus.

INTRODUCTION: Right heart thrombus (RHT), also known as clot in transit, is an uncommon finding in pulmonary embolism (PE) that is associated with increased inpatient mortality. To date, there is no consensus on the management of RHT. Therefore, we aim to describe the clinical features, treatments, and outcomes of patients with simultaneous RHT and PE. METHODS: This is a retrospective, cross-sectional, and single-center study of hospitalized patients with central PE who had RHT visualized on transthoracic echocardiography (TTE) from January 2012 to May 2022. We use descriptive statistics to describe their clinical features, treatments, and outcomes, including mechanical ventilation, major bleeding, inpatient mortality, length of hospital stay, and recurrent PE on follow-up. RESULTS: Of 433 patients with central PE who underwent TTE, nine patients (2%) had RHT. The median age was 63 years (range 29-87), most were African American (6/9), and females (5/9). All patients had evidence of RV dysfunction and received therapeutic anticoagulation. Eight patients received RHT-directed interventions, including systemic thrombolysis (2/9), catheter-directed suction embolectomy (4/9), and surgical embolectomy (2/9). Regarding outcomes, 4/9 patients were hemodynamically unstable, 8/9 were hypoxemic, and 2/9 were mechanically ventilated. The median length of hospital stay was six days (range 1-16). One patient died during hospital admission, and two patients had recurrent PE. CONCLUSION: We described the different therapeutic approaches and outcomes of patients with RHT treated in our institution. Our study adds valuable information to the literature, as there is no consensus on the treatment of RHT. HIGHLIGHTS: Right heart thrombus (RHT) was a rare finding in central pulmonary embolism. Most patients with RHT had evidence of RV dysfunction and pulmonary hypertension. Most patients received RHT-directed therapies in addition to therapeutic anticoagulation.

Adverse fetal and neonatal outcomes following in-utero exposure to oxcarbazepine: A systematic review and meta-analysis.

AIM: This systematic review aims to assess the safety profile of oxcarbazepine during pregnancy. METHODS: Observational studies that included women who took oxcarbazepine anytime during pregnancy were included in our systematic review. The review did not include non-English articles, reviews, meta-analyses, case reports and animal studies. Different online sources such as MEDLINE, Cochrane library, Virtual Health Library, etc., were searched for published and unpublished literature. Assessment of the risk of bias in observational studies was carried out using the Newcastle-Ottawa Scale. The meta-analyses were performed using a random-effect model. GRADE was used for the evaluation of the quality of evidence for the primary outcomes. RESULTS: We included 19 cohort studies with a total of 5 071 137 patients, of which 2450 were exposed to oxcarbazepine either as monotherapy or polytherapy. The summary odds ratio (OR) was 1.69 (95% CI, 0.95-2.98) for congenital malformations following in-utero exposure to oxcarbazepine as compared to the control group of unexposed patients (seven studies [n = 625]), and was 1.19 (95% CI, 0.67-2.12) when compared to those following lamotrigine (LTG) exposure during pregnancy (3 studies [n = 591]). In total, three studies (n = 770) reported the association between in-utero oxcarbazepine exposure and fetal/perinatal deaths. The meta-analysis yielded a summary OR of 3.33 (95% CI, 1.70-6.51). CONCLUSION: Our systematic review will help healthcare providers and guideline developers regarding the treatment of epilepsy and other neurological disorders during pregnancy. More cohort studies with a higher sample size concerning oxcarbazepine use in pregnant patients are required to truly assess the in-utero safety profile of the drug.

Follow Up Imaging in Hepatocellular Cancer Ultrasound Screening Exams With Poor Visualization Scores.

OBJECTIVES: The Ultrasound Liver Imaging Reporting and Data Systems (LI-RADS) provides standardized terminology and reporting for ultrasound (US) examinations performed for hepatocellular cancer (HCC) screening. However, there are no recommendations regarding follow up imaging for visualization scores with suboptimal visualization. Therefore, the aim of this study is to examine follow up imaging practices in the setting of US studies scored as B (moderate limitations) and C (severe limitations). METHODS: A single center retrospective analysis of studies from 2017 to 2021 with HCC US screening visualization scores of B and C was performed. Follow up imaging with US, CT, or MRI within 6 months with visualization score B or C on initial US were included. RESULTS: Five hundred and sixty HCC US studies with suboptimal imaging were reviewed. Of those with follow up imaging, patients with a visualization score of B underwent US in more than half (58%) of the cases while those with visualization score of C underwent more CT/MRI studies (62.5%, P = .12) Patients with visualization score of B had more MRI exams performed (55%) while patients with a visualization score of C underwent more CT exams (70%, P = .16). CONCLUSIONS: Currently, there are no guidelines instructing follow up imaging on HCC screening ultrasounds with poor visualization, and the data suggests that providers have taken a heterogeneous approach. This suggests a need for society recommendations on how to approach HCC screening ultrasounds in patients with suboptimal studies.

Cardiorenal Protection With the Newer Antidiabetic Agents in Patients With Diabetes and Chronic Kidney Disease: A Scientific Statement From the American Heart Association.

Chronic kidney disease (CKD) with type 2 diabetes (T2D) is a major public health problem, resulting in significant cardiovascular and kidney adverse outcomes worldwide. Despite the widespread use of standard-of-care therapies for CKD with T2D over the past few decades, rates of progression to end-stage kidney disease remain high with no beneficial impact on its accompanying burden of cardiovascular disease. The advent of the newer classes of antihyperglycemic agents, including SGLT2 (sodium glucose cotransporter 2) inhibitors and GLP-1 (glucagon-like peptide-1) receptor agonists, has changed the landscape of therapeutic options for patients with CKD with T2D, with demonstration of significant reductions in cardiovascular adverse events and progression to end-stage kidney disease. Several potential mechanisms exist through which these beneficial effects are achieved in both drug classes, which may be independent of their antihyperglycemic effects. This scientific statement summarizes the current literature on the cardiorenal protective effects with SGLT2 inhibitors and GLP-1 receptor agonists in patients with CKD and T2D. It reviews potential mechanistic pathways that may drive these benefits and summarizes the literature on adverse effects in patients with CKD and T2D at risk for or with established cardiovascular disease. Last, it provides practical guidance on a proposed collaborative care model bridging cardiologists, nephrologists, endocrinologists, and primary care physicians to facilitate the prompt and appropriate integration of these therapeutic classes in the management of patients with T2D and CKD.

COVID-19 in HIV-infected patients: A case series and literature review.

During the current COVID pandemic, there is growing interest to identify subsets of the population that may be at a higher than average risk of infection. One such group includes people living with HIV.

Factors associated with hospital readmissions among patients with COVID-19: A single-center experience.

Identify factors associated with readmission after an index hospital admission for coronavirus disease 2019 (COVID-19) infection in a single center serving an underserved and predominantly minority population. This retrospective descriptive study included 275 patients who tested COVID-19 positive via reverse transcriptase-polymerase chain reaction assay at our institution and who survived the index hospitalization. The main outcomes were 1- and 6-month readmission rates after an index hospitalization for COVID-19. The mortality rate among the readmitted patients was also determined. Factors independently associated with readmission were investigated using multivariable logistic regression. A final sample of 275 patients was included. The mean age was 64.69 ± 14.64 (SD), 133 (48%) were female and 194 (70%) were African American. Their chronic medical conditions included hypertension 203 (74%) and diabetes mellitus 121 (44%). After the hospitalization, 1-month readmission rate was 7.6%, while 6-month readmission rate was 24%. Nine percent of patients who were readmitted subsequently died. Coronary artery disease (CAD) was significantly associated with 6-month readmission odds ratio (OR), 2.15 (95% confidence interval [CI]: 1.04-4.44; p = 0.039) after adjustment for age, gender, ethnicity, and comorbidities. Readmissions were due to cardiac, respiratory, and musculoskeletal symptoms. Hispanic ethnicity was associated with increased readmission OR, 3.16 (95% CI: 1.01-9.88; p = 0.048). No significant difference was found between inflammatory markers or clinical outcomes during the index hospitalization among patients who were readmitted compared to those who were not. A significant number of patients hospitalized for COVID-19 may be readmitted. The presence of CAD is independently associated with high rates of 6-month readmission.

Bacterial infections and patterns of antibiotic use in patients with COVID-19.

Bacterial coinfection is associated with poor outcomes in patients with viral pneumonia, but data on its role in the mortality of patients with coronavirus disease 2019 (COVID-19) is limited. This is a single-center retrospective analysis of 242 patients with confirmed COVID-19 admitted to both intensive care and non-intensive care settings. Bacterial coinfection was determined by the presence of characteristic clinical features and positive culture results. Multivariable logistic regression was used to analyze the association of concomitant bacterial infection with inpatient death after adjusting for demographic factors and comorbidities. Antibiotic use pattern was also determined. Bacterial coinfection was detected in 46 (19%) patients. Genitourinary source was the most frequent, representing 57% of all coinfections. The overall mortality rate was 21%. Concomitant bacterial infections were independently associated with increased inpatient mortality (OR, 5.838; 95% CI, 2.647-12.876). Patients with bacterial coinfection were relatively older (71.35 ± 11.20 vs 64.78 ± 15.23; P = .006). A total of 67% of patients received antibiotic therapy, yet 72% did not have an obvious source of bacterial infection. There was a significantly higher rate of inpatient mortality in patients who received antibiotics compared to those who did not (30% vs 5%; P < .0001). Bacterial coinfection in COVID-19 is associated with increased mortality.

Characteristics and clinical outcomes of COVID-19 patients in an underserved-inner city population: A single tertiary center cohort.

There is limited information describing the characteristics and clinical outcomes of patients infected with coronavirus disease 2019 (COVID-19) especially those in underserved urban area with minority population in the United States. This is a retrospective single-center study for patients who were admitted with COVID-19 infection. Data collection was from 1 March through 24 April 2020. Demographic, clinical, laboratory, and treatment data were presented using descriptive statistics and frequencies. The χ2 test and multivariate logistic regression were used to determine association of risk factors and clinical outcomes. A total of 242 inpatients were included with a mean age of 66 ± 14.75 (±standard deviation). A total of 50% were female and 70% were African American. Comorbidities included hypertension (74%), diabetes mellitus (49%), and 19% had either COPD or asthma. Older age was associated with higher risk of inpatient death odds ratio (OR): 1.056 (95% confidence interval [CI]: 1.023-1.090; P = .001). Inpatient mortality occurred in 70% who needed mechanical ventilation (OR: 29.51; 95% CI: 13.28-65.60; P < .0001), 58% who required continuous renal replacement therapy/hemodialysis (CRRT/HD) (OR: 6.63; 95% CI: 2.74-16.05; P < .0001), and 69% who needed vasopressors (OR: 30.64; 95% CI: 13.56-69.20; P < .0001). Amongst biomarkers of disease severity, only baseline CRP levels (145 ± 116 mg/L) were associated with mortality OR: 1.008 (95% CI: 1.003-1.012; P = .002). Majority of hospitalized patients had hypertension and diabetes. Older age was an independent risk factor for inpatient mortality. Requirement of mechanical ventilation, vasopressor use, and CRRT/HD was associated significantly with inpatient mortality. Higher baseline CRP was significantly associated with inpatient death.

Etiologies and predictors of readmission among obese and morbidly obese patients admitted with heart failure.

The relationship between severity of obesity and outcomes in heart failure (HF) has long been under debate. We studied index HF admissions from the 2013-14 National Readmission Database. Admissions were separated into three weight-based categories: non-obese (Non-Ob), obese (Ob), and morbidly obese (Morbid-Ob) to analyze hospital mortality and readmission at 30 days and 6 months. We investigated etiologies and predictors of 30-day readmission among these weight categories. We studied a total of 578,213 patients of whom 3.0% died during index hospitalization (Non-Ob 3.3% vs. Ob 1.9% vs. Morbid-Ob 1.9%; p < 0.01). Non-Ob comprised 79.5%, Ob 9.9%, and Morbid-Ob 10.6% of patients. Morbid-Ob patients were the youngest among age categories and more likely to be female. In-hospital mortality during readmission at 30 days and 6 months was significantly lower among Morbid-Ob and Ob compared with Non-Ob patients (all p < 0.01). Thirty-day readmission among Morbid-Ob was lower than Non-Ob and higher than Ob patients (19.6% vs. 20.5% vs. 18.6%, respectively; p < 0.01). Morbid-Ob patients were less likely to be readmitted for cardiovascular etiologies compared with both Ob and Non-Ob (45.0% vs. 50.3% vs. 50.6%; p < 0.01). Multivariable regression analysis revealed that Ob (adjusted odds ratio 0.84, 95% confidence intervals 0.82-0.86) and Morbid-Ob (aOR 0.83, 95% CI 0.81-0.85) were independently associated with lower 30-day readmission. Readmission at 6 months was highest among Morbid-Ob followed by Non-Ob and Ob (51.1% vs. 50.2% vs. 49.1%, p < 0.01). Morbid-Ob and Ob patients experience lower in-hospital mortality during index HF admission and during readmission with 30 days or 6 months compared with Non-Ob. Morbid-Ob patients experience greater readmission at 6 months despite the lower rate at 30 days post discharge. Morbid-Ob patients are most likely to be readmitted for non-cardiovascular causes.

Clinical outcomes in patients with heart failure with and without cirrhosis: an analysis from the national inpatient sample.

Outcomes of heart failure (HF) hospitalization are driven by the presence or absence of comorbid conditions. Cirrhosis is associated with worse outcomes in patients with HF, and both HF and cirrhosis are associated with worse renal outcomes. Using a nationally representative sample we describe inpatient outcomes of all-cause mortality and length of stay (LOS) among patients with and without cirrhosis hospitalized for decompensated with HF. We conducted a cross sectional analysis using Nationwide Inpatient Sample (2010-2014) data including patients hospitalized for decompensated HF, with or without cirrhosis. We calculated the adjusted odds of all-cause mortality, acute kidney injury (AKI), and target LOS after adjusting for potential confounders. Out of the 2,487,445 hospitalized for decompensated HF 39,950 had cirrhosis of which majority (75.1%) were non-alcoholic cirrhosis. Patients with comorbid cirrhosis were more likely to die (OR, 1.26; 95% CI, 1.11 to 1.43) and develop AKI (OR, 1.26; 95% CI, 1.16 to 1.36) as compared to those without cirrhosis. Underlying CKD was associated with a greater odds of AKI (OR, 4.99; 95% CI, 4.90 to 5.08), and the presence of cirrhosis amplified this risk (OR, 6.03; 95% CI, 5.59 to 6.51). There was approximately a 40% decrease in the relative odds of lower HF hospitalization length of stay among those with both CKD and cirrhosis, relative to those without either comorbidities. Cirrhosis in patients with hospitalizations for decompensated HF is associated with higher odds of mortality, decreased likelihood of discharge by the targeted LOS, and AKI. Among patients with HF the presence of cirrhosis increases the risk of AKI, which in turn is associated with poor clinical outcomes.

Angiotensin converting enzyme inhibitors and angiotensin receptor blockers in acute heart failure: invasive hemodynamic parameters and clinical outcomes.

There are limited data regarding the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) in acute heart failure (AHF). The purpose is to determine the patterns of ACEi/ARB use at the time of admission and discharge in relation to invasive hemodynamic data, mortality, and heart failure (HF) readmissions. This is a retrospective single-center study in patients with AHF who underwent right heart catheterization between January 2010 and December 2016. Patients on dialysis, evidence of shock, or incomplete follow up were excluded. Multivariate logistic regression analysis was used to analyze the factors associated with continuation of ACEi/ARB use on discharge and its relation to mortality and HF readmissions. The final sample was 626 patients. Patients on ACEi/ARB on admission were most likely continued on discharge. The most common reasons for stopping ACEi/ARB were worsening renal function (WRF), hypotension, and hyperkalemia. Patients with ACEi/ARB use on admission had a significantly higher systemic vascular resistance (SVR) and mean arterial pressure (MAP), but lower cardiac index (CI). Patients with RA pressures above the median received less ACEi/ARB (P = 0.025) and had significantly higher inpatient mortality (P = 0.048). After multivariate logistic regression, ACEi/ARB use at admission was associated with less inpatient mortality; OR 0.32 95% CI (0.11 to 0.93), and this effect extended to the subgroup of patients with HFpEF. Patients discharged on ACEi/ARB had significantly less 6-month HF readmissions OR 0.69 95% CI (0.48 to 0.98). ACEi/ARB use on admission for AHF was associated with less inpatient mortality including in those with HFpEF.