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Kevin Bryan Lo,1 Jeri Albano,1 Naemat Sandhu,2 Nellowe Candelario11Department of Medicine, Einstein Medical Center, Philadelphia, PA, USA; 2Department of Gastroenterology and Hepatology, Einstein Medical Center, Philadelphia, PA, USAAbstract: Plummer-Vinson syndrome is a rare condition associated with dysphagia, iron deficiency, and esophageal webs. Data regarding this condition is limited to mostly case reports and a few small cohort studies. Although most cases have a benign and indolent course, the risk of malignancy warrants long-term surveillance. A multidisciplinary approach among healthcare providers is of the utmost importance in the management of this condition.Keywords: esophageal webs, iron deficiency anemia, dysphagia, malignancy

Background: Pulmonary hypertension (pH) is a well-known complication among patients with chronic kidney disease (CKD). Arteriovenous fistulae (AVF) have been associated with pH mainly by increasing cardiac output. However, the burden of precapillary pH in individuals with CKD and an AVF is unclear., Objectives: To better and more fully understand the mechanism and development of precapillary pH in patients with AVF, as well as the consequences of precapillary pH in these patients., Methods: This was a large retrospective study of patients with CKD stage 4 or 5 who underwent right heart catheterization (RHC) from 2018 to 2023. The data were stratified according to the presence of AVF. To determine if AVF was independently associated with precapillary pH, we used a multivariable logistic regression analysis adjusting for demographics and potential comorbidities associated with precapillary pH, including diagnosis of chronic lung disease, obstructive sleep apnea, connective tissue disease, history of venous thromboembolism, chronic anemia, and heart failure., Results: Of 651 patients with CKD4 or CKD5, 145 (22 %) had AVF and 506 (78 %) did not have AVF. Within the AVF group, the median age was 64 years (IQR 54-71), and they were predominantly males (61 %, n = 88) and African American (77 %, n = 111). A total of 31 % (n = 45) had evidence of precapillary pH, 30 % (n = 43) of combined pH, and 14 % (n = 20) of isolated postcapillary pH. Compared to the non-AVF group, precapillary pH was more likely in the AVF group (31% vs 17 %, p < 0.0001). On multivariable analysis, AVF was independently associated with precapillary pH (OR 2.47, CI 1.56-3.89; p < 0.0001). The median time from dialysis initiation to RHC date (and precapillary pH diagnosis) was 6 years (IQR 3-8)., Conclusion: Based on RHC findings, almost one-third of patients with CKD and AVF had precapillary pH. The presence of AVF was independently associated with precapillary pH., Competing Interests: Declaration of competing interest The authors have no competing interest to disclose. None declared., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Despite advances in the diagnosis and therapeutics strategies for pulmonary hypertension (PH) in patients with end-stage liver disease (ESLD), the impact of hemodynamic patterns among ESLD patients identified through right heart catheterization (RHC) on clinical outcomes remains poorly understood., Methods: This single-center retrospective cohort study identified patients diagnosed with ESLD who underwent RHC from August 2018 to June 2023. Demographic and clinical data, including comorbidities, transthoracic echocardiography, and RHC findings, were obtained. Our outcomes of interest were all-cause mortality and the chance of receiving orthotopic liver transplantation (OLT) within a year after RHC. Kaplan-Meier with log-rank test was employed to generate survival curves., Results: We identified 415 ESLD patients with the RHC results. The median (IQR) age was 59 years (52-66), and 62% were male. Caucasians accounted for 43%, followed by African Americans (30%). Up to 89% had a diagnosis of portal hypertension. Median MELD-Na score was 30 (19-36). The etiology of ESLD was mainly from alcohol use (55%). Patients were classified based on RHC results as pre-capillary PH (19%), post-capillary PH (28%), and non-PH (53%) groups. Overall, one-year mortality post-RHC was 22%, with no significant difference in mortality regardless of hemodynamic group. However, the pre-capillary PH group was less likely to receive OLT compared to other groups ( P  < 0.001)., Conclusion: We observed no difference in all-cause mortality among hemodynamic groups. However, pre-capillary PH group were less likely to undergo OLT compared to others. Further investigations are necessary to determine how this should be addressed in clinical practice., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Competing Interests: Declaration of competing interest There is no conflict of interest.

Pulmonary hypertension (PH) is a prevalent complication among patients with chronic kidney disease (CKD). In these patients, pulmonary vasodilators may be useful but are underused. We describe a group of patients with precapillary PH and advanced CKD treated with pulmonary vasodilators. This was a case series of patients with CKD stage 4 and 5 and precapillary PH (isolated or combined) based on right heart catheterization (RHC) treated with pulmonary vasodilators from 2018 to 2023. Of 263 patients with isolated precapillary or combined PH and advanced CKD, only 17 (6%) were treated with pulmonary vasodilators; 53% ( n  = 9) with precapillary PH and 47% ( n  = 8) with combined PH. Most patients (94%, n  = 16) received phosphodiesterase-5 antagonists, while 12% ( n  = 2) received endothelin receptor antagonists. Adverse clinical outcomes were seen in 35% of patients within a year. The use of pulmonary vasodilator did not prevent adverse outcomes in patients with precapillary PH and advanced CKD., Competing Interests: Given the adherence to ethical and institutional guidelines and the main incentive of academic growth without monetary incentive for the development of this study, the authors declare no conflicts of interest present in this study., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Objective: Systemic lupus erythematosus (SLE) is characterized by widespread organ inflammation. Metformin, commonly used for diabetes mellitus type 2, has been explored for its anti-inflammatory potential in SLE. This study investigates the association of metformin use on renal and cardiovascular outcomes in patients with SLE., Methods: This is a retrospective study. We used the multicenter research network (TriNetX) database from 88 health care organizations globally. Patients with SLE aged 18 and above, admitted between January 1, 2014, and April 21, 2024, were included. Propensity score matching compared patients with SLE on metformin with those not on metformin, considering demographics, laboratory results, comorbidities, and baseline medication use. The study assessed outcomes, including lupus nephritis (LN), chronic kidney disease (CKD), and major adverse cardiovascular events (MACEs) at one and five years after SLE diagnosis., Results: We identified 9,178 patients with SLE on metformin and 78,983 patients with SLE not on metformin. After propensity score matching, patients with SLE on metformin had higher levels of hemoglobin A1C, whereas patients not on metformin had higher levels of urea nitrogen. When comparing both groups, the risk of developing LN (risk ratio [RR] = 1.70 [1.17-2.41]; P = 0.004), CKD (RR = 1.27 [1.07-1.52]; P = 0.007), and MACEs (RR = 1.21 [1.00-1.46]; P = 0.04) was significantly higher among patients not on metformin at one year after SLE diagnosis. After five years, the risk of LN and CKD was also higher in patients with SLE not on metformin. MACE risk was no longer significant after five years of diagnosis between both groups., Conclusion: Patients with SLE not on metformin have a higher risk of developing LN, CKD, and MACEs compared with patients treated with metformin. Metformin's anti-inflammatory potential offers promise as a complementary therapy for SLE. Nonetheless, further research and clinical trials are needed to clarify its mechanisms, optimal dosage, and long-term effects., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Patients who had acute myocardial infarction are at high risk of negative cardiac outcomes and previous SGLT2i landmark trials excluded these patients. It therefore remains unclear if SGLT2i is safe and confers beneficial cardiovascular outcomes after acute myocardial infarction., Methods: We systematically reviewed randomized controlled trials that evaluated the outcomes of adding SGLT2i to conventional post-myocardial infarction care. Random-effects model meta-analysis via RevMan 5.4 was done on data extracted from pooled 11,204 patients., Results: SGLT2i use after acute myocardial infarction was significantly associated with reduced heart failure hospitalization (OR: 0.77, 95%CI: 0.62-0.96, p=0.02), but was not associated with a reduction in all-cause mortality (OR: 1.05, 95%CI: 0.77-1.43, p=0.75), cardiac-related death (OR: 1.04, 95%CI: 0.83-1.30, p=0.76), or major adverse cardiac events (OR: 0.90, 95%CI: 0.77-1.05, p=0.18)., Conclusion: SGLT2 inhibitor therapy after acute myocardial infarction is safe and is associated with a reduced risk of heart failure hospitalization, but not with all-cause mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Midodrine, an FDA-approved medication for orthostatic hypotension, is also used off-label to manage hypotension in dialysis patients, including those with heart failure. However, in patients with reduced ejection fraction (HFrEF) and/or right heart failure, midodrine is potentially harmful. No known studies examine the safety of midodrine in hospitalised kidney failure patients with HF., Methods: The TriNetX database was queried for hospitalised kidney failure patients with HFrEF and/or right heart failure who experienced hypotension (SBP < 110 mm Hg or MAP < 70 mm Hg). Excluding those needing critical care or vasopressors, we compared cohorts based on midodrine use, matching for comorbidities., Results: Analysis showed patients on midodrine had a higher 6-month mortality risk ratio (RR 1.53, 95% CI 1.037 to 2.246) and Hazard Ratio (HR 1.54, 95% CI 1.022 to 2.317) compared to those not on midodrine, indicating an association with increased mortality., Conclusion: This study illuminates the complexities in treating hospitalised patients with kidney failure and HF. Our findings, drawn from an exploratory analysis, indicate that inpatient midodrine use is associated with increased 6-month mortality. This may reflect deleterious effects from vasoconstriction and/or unmeasured confounders in this vulnerable population. This investigation, utilising TriNetX, was limited by access to deidentified aggregate data, preventing detailed exploration of specifics such as timing, dosage, and indications for midodrine use. Moreover, given its observational nature, cause-effect relationship cannot be established. Our findings indicate an increased mortality associated with midodrine use for hypotension, underscoring the need for further research and consideration of alternative strategies.

Pulmonary hypertension (PH) is associated with adverse outcomes in chronic kidney disease (CKD) patients. Our study suggests mildly elevated pulmonary vascular resistance ( > 2 to ≤ 3) is independently associated with major adverse cardiovascular events at 1-year follow-up. Early diagnosis of precapillary PH in CKD patients can potentially improve clinical outcomes., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

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., (© 2023 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

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.

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.

Background: Guideline recommendations regarding the preferred preventive measures for postoperative atrial fibrillation (POAF) are unclear, nor have we found any review articles addressing the combination of amiodarone and beta-blockers for the prevention of POAF., Objectives: To investigate the efficacy and safety of combination beta-blockers and amiodarone in the prevention of POAF while also comparing the use of amiodarone and beta-blockers individually., Methods: We used Pubmed as the primary resource. POAF incidence was the primary outcome of this study. The secondary outcomes were hospital length of stay (LOS), ICU LOS, treatment-related drug discontinuation (TRDD), and mortality. The random-effects model assessed all pooled outcomes with 95% confidence intervals. Statistical significance was set at p≤0.05., Results: The amiodarone subgroup of POAF incidence saw a Risk Ratio (RR) of 0.81 [0.63, 1.06], p=0.12, while the combination subgroup resulted in a RR of 0.63 [0.49, 0.80], p <0.001. TRDD for the amiodarone subgroup resulted in a RR of 0.68 [0.25, 1.82], p=0.44, while the combination subgroup saw a RR of 0.84 [0.57, 1.23], p=0.36. For mortality, the amiodarone subgroup resulted in a RR of 0.97 [0.48, 1.98], p=0.93, while the combination subgroup resulted in a RR of 1.04 [0.27, 4.05], p=0.96. Both hospital and ICU LOS saw no significant difference between treatment arms for both the combination subgroup and amiodarone alone. Except for the incidence of postoperative atrial fibrillation (POAF) in the combination prophylaxis group, most of the measured outcomes did not meet the optimized information size (OIS) that was estimated., Conclusion: Combination prophylaxis with amiodarone and beta-blockers significantly lowered risks of POAF incidence in comparison to beta-blockers alone while also having comparative mortality and TRDD outcomes., Competing Interests: Declaration of Competing Interest There are no competing financial interests or relationships between the authors of this meta-analysis and any entities that could have affected the results of this review., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare.

Background: There is paucity of data regarding the impact of concomitant heart failure (HF) on the in-hospital outcomes among hospitalized sarcoidosis patients. We aim to investigate the factors associated with concomitant HF and its impact on in-hospital outcomes among hospitalized sarcoidosis patients., Methods: We utilized the 2018-2020 National Inpatient Sample (NIS) Database in conducting this study. Multivariable logistic and linear regression models were used to examine the factors associated with HF and hospital-associated outcomes among patients with sarcoidosis., Results: A total of 36,864 hospitalized patients with sarcoidosis were identified, of which 24.78 % (n = 9135/36,864) had concomitant HF. Factors associated with concomitant HF were age (aOR 1.03; 95 % CI: 1.02-1.03, p value ≤ 0.001), black race (aOR 1.74; 95 % CI: 1.47-2.05, p value ≤ 0.001), not being female (aOR 0.79; 95 % CI: 0.69-0.91, p value ≤ 0.001), and arrhythmias (aOR 2.50; 95 % CI: 2.10-2.98, p value ≤ 0.001) specifically atrial fibrillation and ventricular tachycardia. Comorbidities associated with concomitant HF in this population were hyperlipidemia, obesity, coronary artery disease, cardiac device implantation history, and chronic kidney disease stage 1-4. Concomitant HF was not an independent predictor of in-hospital mortality or length of stay (LOS). However, age (aOR 1.04; 95 % CI, 1.03-1.06; p ≤ 0.001) and arrhythmia burden (aOR 2.08; 95 % CI, 1.47-2.95; p ≤ 0.001), specifically ventricular tachycardia and fibrillation, were independently associated with in-hospital mortality among sarcoidosis patients., Conclusion: Traditional cardiovascular risk factors were associated with concomitant HF among hospitalized sarcoidosis patients. Moreover, concomitant HF among sarcoidosis patients was not significantly associated with in-hospital mortality or LOS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Introduction: Cirrhosis-associated immune dysfunction (CAID) is a chronic vasodilatory state with hyperdynamic circulation and alterations in thermoregulation that may make patients more susceptible to and mask underlying infection. This study aims to determine whether SIRS criteria are an accurate tool for predicting bloodstream infection (BSI) in cirrhosis., Methods: In our retrospective chart review, study population included patients with cirrhosis that were 18 years or older. For all study patients, model for end-stage liver disease (MELD) scores and values for each SIRS variable at the time of admission and blood culture data were recorded. Univariable and multivariable logistic regression analysis was performed to identify any associations between dichotomized SIRS variables that fulfill SIRS positivity and BSI., Results: Significantly more patients without BSI met positivity criteria for WBC counts (30% vs 13% p < .001). In the analysis of the SIRS variables as continuous variables in prediction of BSI, the AUC curves generated were all unsatisfactory with the temperature (36-38°C) and WBC count (4 × 10 3 to 12 × 10 3 mcL) at the time of admission having the highest areas under the ROC curve (0.52 and 0.55, respectively). Looking at the SIRS variables dichotomized (according to whether fulfilling SIRS criteria or not) in univariable logistic regression, only WBC counts meeting SIRS criteria were significantly associated with BSI OR 0.37 (0.18-0.77); p  = .008, but this was an inverse association. This association was true even in the multivariable model OR 0.38 (0.18-0.80); p  = .01., Conclusion: Our study shows that SIRS criteria are a poor predictor of BSI among patients with cirrhosis., Competing Interests: We have no conflicts of interest to disclose with this original piece of research.

Background: In prior studies, central pulmonary embolism (PE) was associated with high clot burden and was considered an independent predictor for thrombolysis. Further information about predictors of adverse outcomes in these patients is needed for better risk stratification. The objective is to describe independent predictors of adverse clinical outcomes in patients with central PE., Methods: Large retrospective, observational, and single-center study of hospitalized patients with central PE. Data were gathered on demographics, comorbidities, clinical features on admission, imaging, treatments, and outcomes. Multivariable standard and Least Absolute Shrinkage and Selection Operator (LASSO) machine learning logistic regressions and sensitivity analyses were used to analyze factors associated with a composite of adverse clinical outcomes, including vasopressor use, mechanical ventilation, and inpatient mortality., Results: A total of 654 patients had central PE. The mean age was 63.1 years, 59% were women, and 82% were African American. The composite adverse outcome was observed in 18% (n = 115) of patients. Serum creatinine elevation (odds ratio [OR] = 1.37, 95% CI = 1.20-1.57; p = 0.0001), white blood cell (WBC) count elevation (OR = 1.10, 95% CI = 1.05-1.15; p < 0.001), higher simplified pulmonary embolism severity index (sPESI) score (OR = 1.47, 95% CI = 1.18-1.84; p = 0.001), serum troponin elevation (OR = 1.26, 95% CI 1.02-1.56; p = 0.03), and respiratory rate increase (OR = 1.03, 95% CI = 1.0-1.05; p = 0.02) were independent predictors of adverse clinical outcomes., Conclusion: Among patients with central PE, higher sPESI score, WBC count elevation, serum creatinine elevation, serum troponin elevation, and respiratory rate increase were independent predictors of adverse clinical outcomes. Right ventricular dysfunction on imaging and saddle PE location did not predict adverse outcomes., Competing Interests: Declaration of competing interest The authors have no competing interest to disclose. None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Given the heterogeneity of predisposing factors associated with pulmonary infarction (PI) and the lack of clinically relevant outcomes among patients with acute pulmonary embolism (PE) complicated by PI, further investigation is required., Methods: Retrospective study of patients with central PE in an 11-year period. Data were stratified according to the diagnosis of PI. Multivariable logistic regression analysis was used to analyze factors associated with PI development and determine if PI was associated with severe hypoxemic respiratory failure and mechanical ventilation use., Results: Of 645 patients with central PE, 24% ( n  = 156) had PI. After adjusting for demographics, comorbidities, and clinical features on admission, only age (OR 0.98, CI 0.96-0.99; p  = 0.008) was independently associated with PI. Regarding outcomes, 35% ( n  = 55) had severe hypoxemic respiratory failure, and 19% ( n  = 29) required mechanical ventilation. After adjusting for demographics, PE severity, and right ventricular dysfunction, PI was independently associated with severe hypoxemic respiratory failure (OR 1.78; CI 1.18-2.69, p  = 0.005) and mechanical ventilation (OR 1.92; CI 1.14-3.22, p  = 0.013)., Conclusions: Aging is a protective factor against PI. In acute central PE, subjects with PI had higher odds of developing severe hypoxemic respiratory failure and requiring mechanical ventilation.

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.

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., (© 2023 Wiley Periodicals LLC.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Patients with advanced chronic kidney disease (CKD) have largely been excluded from randomized control trials (RCTs) in heart failure (HF). This creates a paucity of high quality evidence for guideline directed medical therapy (GDMT), particularly in patients with heart failure with reduced ejection fraction (HFrEF) and CKD. This is a systematic review looking at the patterns and rates of inclusion of CKD in RCTs among patients with HFrEF. The search included RCTs from January 2010 to December 2020. A heat map was constructed to reflect the stages of CKD stages. The percentage of studies that included advanced CKD (stages IV-V) was recorded and log transformed, and then fitted into a time regression model. A P value of <0.05 was considered statistically significant. Out of the 3052 screened, 706 studies were included in the analysis. Only 61% of the RCTs reported at least some information on kidney function. There was a trend of increase in percentage of studies that included CKD stages IV-V from years 2010 to 2020. This was confirmed with a statistically significant linear trend P = 0.02 while the percentage of studies that included dialysis and kidney transplant recipients remained consistently low. There is a paucity of high-quality evidence for GDMT in the HFrEF population with CKD, particularly in those with advanced non-dialytic CKD, those on maintenance dialysis and kidney transplant recipients. There is a pressing need for wider inclusion of patients with advanced CKD in RCTs of GDMT in HFrEF., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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/1.73m 2 or continuously across a wide range of eGFR (P interaction > 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., Competing Interests: Disclosures CAH reports consulting for AstraZeneca, Bayer, Fibrogen, Merck, Diamedica, Boston Scientific, University of Oxford, University of British Columbia; research grants from BristolMyersSquibb, Pfizer; stock ownership in General Electric, Johnson&Johnson; employer in Hennepin Healthcare; author royalties. MV has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; speaks at Novartis and Roche Diagnostics, and participates on clinical trial committees for studies sponsored by Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. JR has served on the advisory boards for Procyrion and as a consultant for Boehringer Ingelheim-Lily, Astra Zeneca and Edwards Lifesciences. ROM is an employer at Loma Linda Veterans Affairs Health Care System and is a consultant for Procyrion and Clinical Trials Endpoint Committee and reports stock ownership in Apple, Lowes, Corning, and Snowflake. All other authors report no disclosures., (Published by Elsevier Inc.)

Background: Our prior analysis demonstrated no significant difference in risk of mortality or disease progression among patients with COVID-19. With the availability of findings from randomized controlled trials (RCTs), we provide an updated review of RCTs which explored the outcomes among hospitalized patients with COVID-19 treated with Angiotensin Converting Enzyme inhibitor (ACEis)/Angiotensin Receptor Blockers (ARBs) versus control., Research Design and Methods: This systematic review and meta-analysis covers RCTs exploring mortality, intensive care unit admission, and mechanical ventilation outcomes among hospitalized COVID-19 patients treated with ACEi/ARBs., Results: Ten studies were included in this meta-analysis. For mortality with ACEi/ARB utilization among hospitalized COVID-19 patients, the pooled risk ratio (RR) was 0.97 (95% CI 0.64-1.47, p = 0.89) with heterogeneity of 26%. Further, the pooled RR for ACEi/ARB use on ICU admission and mechanical ventilation were 0.55 (0.55-1.08, p = 0.13) with a heterogeneity of 0% and 1.02 (0.78-1.32, p = 0.91) with a heterogeneity of 0%, respectively., Conclusion: Among hospitalized patients with COVID-19, the use of ACEi/ARB was not associated with increased risk of mortality, ICU admission, or mechanical ventilation compared to control. These findings support continuation of ACEi/ARB for whom baseline clinical indications for these agents exist.

Introduction: Angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRA) reduce mortality and hospitalizations in heart failure with reduced ejection fraction (HFrEF) but their use is limited in advanced chronic kidney disease (CKD)., Methods: We carried out a systematic review of studies on HFrEF and CKD patients. The mean overall percentage of reported ACEI, ARB, MRA, and ARNI use, and the proportion of trials that included patients with advanced CKD grades 4-5 (estimated glomerular filtration rate (eGFR) <15-30 ml/min/1.73m 2 ) were recorded per year. The proportion of trials with advanced CKD was logtransformed, and then fitted into a time regression model. The interactions between the proportion of trials that included CKD grades 4-5 and the proportion of reported use of ACEI, ARB, and MRAs per year were explored using Pearson's correlation and univariate linear regression., Results: A total of 706 articles were included; 76% reported background ACEI/ARB use, while 51% reported MRA use. ACEI/ARB use averaged 83% and MRA 50%. Of the trials, 57% included CKD grades 4-5. Over 10 years, the proportion of trials with CKD grades 4-5 increased while ACEI/ARB use decreased. MRA use rates remained about the same. There was an inverse association found between the proportion of trials with CKD grades 4-5 and ACEI/ARB use per year., Conclusion: In the past 10 years, CKD grades 4-5 patients have been increasingly included in HFrEF clinical trials. Concurrently, ACEI/ARB use has reportedly decreased., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: There is paucity of data regarding the characteristics and outcomes of patients admitted for ST Elevation Myocardial Infarction (STEMI) complicated by cardiogenic shock (CS) with concomitant Coronavirus Disease 2019 (COVID-19) infection., Methods: Using the National Inpatient Sample (NIS) Database for the year 2020, we conducted a retrospective cohort study to investigate the outcomes of patients who sustained STEMI-associated cardiogenic shock (STEMI-CS) with concomitant COVID-19 infection looking at its impact on in-hospital mortality and secondarily at the in-hospital procedure and intervention utilization rates as well as hospital length of stay., Results: We identified a total of 22,775 patients with STEMI-CS, of which 1.71 % (n = 390/22,775) had COVID-19 infection. Using a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, concomitant COVID-19 infection among STEMI-CS patients was found to be an independent predictor of overall in-hospital mortality compared to those without COVID-19 (adjusted OR 2.10; 95 % confidence interval [CI], 1.30-3.40). STEMI-CS patients with concomitant COVID-19 infection had similar in-hospital utilization rates for percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), extracorporeal membrane oxygenation (ECMO), percutaneous and durable left ventricular device, intra-arterial aortic balloon pump (IABP), renal replacement therapy (RRT), mechanical ventilation, as well as similar hospital lengths of stay., Conclusion: Concomitant COVID-19 infection was associated with higher in-hospital mortality rates among patients with cardiogenic shock related to STEMI but had similar in-hospital procedure and intervention utilization rates as well as hospital length of stay., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

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., (© 2022 American Institute of Ultrasound in Medicine.)

Objective: To investigate whether Adjunctive PD-1 inhibitors have improved clinical outcomes compared to chemotherapy alone in platinum-pretreated and platinum-naive recurrent or metastatic nasopharyngeal carcinoma (R/M NPCA)., Methods: The study involved a literature search from PubMed, Cochrane CENTRAL, and Google Scholar for randomized clinical trials (RCTs) on the use of PD-1 inhibitors versus chemotherapy alone in patients with R/M NPCA. Bias was assessed using Cochrane collaboration's risk of bias tool. Overall Survival (OS) was examined as the primary endpoint. Secondary endpoints were Progression-Free Survival (PFS), Objective Response Rate, Disease Control Rate (DCR), Duration of Response, and Serious/Grade ⩾3 Adverse Events. Outcomes were measured with either Mean Difference, Risk ratio (RR), or Hazard ratios (HRs) at 95% confidence interval., Results: Four RCTs were included in the meta-analysis and systematic review. OS for the monotherapy subgroup was a HR of 0.87 [0.67, 1.13] ( p  = 0.30) while the combination subgroup had 0.64 [0.45, 0.90] ( p  = 0.01). The monotherapy subgroup exhibited significantly worse outcomes in PFS (HR 1.31 [1.01, 1.68]) ( p  = 0.04) and DCR (RR 1.52 [1.12, 2.05]) ( p  = 0.007) but no significant difference in other outcomes. For combination therapy, a statistically significant benefit can be seen in all outcomes except DCR (RR 0.62 [0.38, 1.01]) ( p  = 0.06) which was a non-significant benefit favoring PD-1 inhibitors., Conclusion: Combination PD-1 inhibitor + chemotherapy followed by maintenance PD-1 inhibitor therapy is superior to chemotherapy alone in the first-line treatment of R/M NPCA, implying a potential benefit with the use of PD-1 inhibitors + chemotherapy with maintenance PD-1 inhibitors as first-line in R/M NPCA compared to standard chemotherapy alone., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2022.)

There are limited data on clinical outcomes in patients re-admitted with decompensated heart failure (HF) with concomitant liver cirrhosis. We conducted a cross sectional analysis of the Nationwide Readmissions Database (NRD) years 2010 thru 2012. An Index admission was defined as a hospitalization for decompensated heart failure among persons aged ≥ 18 years with an alive discharge status. The main outcome was 30 - day all-cause rehospitalization. Survey logistic regression provided the unadjusted and adjusted odds of 30 - day rehospitalization among persons with and without cirrhosis, accounting for age, gender, kidney dysfunction and other comorbidities. There were 2,147,363 heart failure (HF) hospitalizations among which 26,156 (1.2%) had comorbid cirrhosis. Patients with cirrhosis were more likely to have a diagnosis of acute kidney injury (AKI) during their index hospitalization (18.4% vs 15.2%). There were 469,111 (21.9%) patients with readmission within 30 - days. The adjusted odds of a 30 - day readmission was significantly higher among patients with cirrhosis compared to without after adjusting for comorbid conditions (adjusted Odds Ratio [aOR], 1.3; 95% Confidence Interval [CI}: 1.2 to 1.4). The relative risk of 30 - day readmission among those with cirrhosis but without renal disease (aOR, 1.3; 95% CI: 1.3 to 1.3) was lower than those with both cirrhosis and renal disease (aOR, 1.8; 95% CI: 1.6 to 2.0) when compared to persons without either comorbidities. Risk of 30 - day rehospitalization was significantly higher among patients with heart failure and underlying cirrhosis. Concurrent renal dysfunction among patients with cirrhosis hospitalized for decompensated HF was associated with a greater odds of rehospitalization., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) may result in rapid onset of hypoxemic respiratory failure. This study aimed to characterize the factors and outcomes associated with prolonged hypoxia in patients with COVID-19. Prolonged severe hypoxia (PSH) was defined as hypoxia requiring ≥6 L/min of oxygen by nasal cannula or equivalent for more than 10 days., Research Design and Methods: This study was designed as a single-center retrospective analysis. Multivariable logistic regression was utilized to assess factors associated with PSH., Results: The sample included 554 patients with 117 (21%) having PSH. Median length of stay of patients with PSH was significantly longer (median IQR: 18 days vs 6 days, p < 0.0001). Patients with PSH had significantly higher rates of venous thromboembolism (p < 0.0001) and major bleeding (p < 0.004). The presence of cirrhosis (OR 3.32, 95% CI [1.02 to 10.83]) and hypertension (OR 1.99, 95% CI [1.12 to 3.53]) were independently associated with PSH, while outpatient use of anti-platelet agents had an inverse association (OR 0.57, 95% CI [0.36 to 0.91])., Conclusion: PSH is associated with increased length of stay, morbidity, and mortality. Hypertension and liver cirrhosis were significantly associated with higher odds of PSH, while use of anti-platelet therapy had a protective effect.

Mechanistic Insights in Cardiorenal SyndromeLo and Rangaswami review the pathophysiology and management of cardiorenal syndrome, with a focus on decongestion, interpretation of kidney function, and implementation of guideline directed medical therapies.

In this systematic review, we seek to clarify the impact of treatment of hyperthyroidism on pulmonary hypertension in patients with both these conditions. We included 39 of 709 articles retrieved, that studied patients with hyperthyroidism and pulmonary hypertension (PH). From these, those with a documented pre-treatment Pulmonary Artery Systolic Pressure (PASP) > 35 mmHg and complete follow up were analyzed, yielding 3 case series and 22 case reports with a total of 81 cases. A significant improvement in PASP was noted with achieving euthyroidism in the 3 case series. The case reports showed a significant reduction in mean PASP from 60.5 ± 13.2 mmHg to 37.5 ± 10.1 mmHg (p < 0.001) in patients with Grave's disease with achieving euthyroidism. No deaths were reported during the follow up period. Achievement of a euthyroid state in patients with hyperthyroidism is associated with statistically significant reductions in PASP., Competing Interests: None., (AJCD Copyright © 2022.)

Background: Hepatorenal syndrome (HRS), a form of kidney dysfunction frequent in cirrhotic patients, is characterized by low filling pressures and impaired kidney perfusion due to peripheral vasodilation and reduced effective circulatory volume. Cardiorenal syndrome (CRS), driven by renal venous hypertension and elevated filling pressures, is a separate cause of kidney dysfunction in cirrhotic patients. The two entities, however, have similar clinical phenotypes. To date, limited invasive hemodynamic data are available to help distinguish the primary forces behind worsened kidney function in cirrhotic patients., Objective: Our aim was to analyze invasive hemodynamic profiles and kidney outcomes in patients with cirrhosis who met criteria for HRS., Methods: We conducted a single center retrospective study among cirrhotic patients with worsening kidney function admitted for liver transplant evaluation between 2010 and 2020. All met accepted criteria for HRS and underwent concurrent right heart catheterization (RHC)., Results: 127 subjects were included. 79 had right atrial pressure >10 mmHg, 79 had wedge pressure >15 mmHg, and 68 had both. All patients with elevated wedge pressure were switched from volume loading to diuretics resulting in significant reductions between admission and post diuresis creatinine values (2.0 [IQR 1.5-2.8] vs 1.5 [IQR 1.2-2.2]; p = 0.003)., Conclusion: 62% of patients diagnosed with HRS by clinical criteria have elevated filling pressures. Improvement of renal function after diuresis suggests the presence of CRS physiology in these patients. Invasive hemodynamic data profiling can lead to meaningful change in management of cirrhotic patients with worsened kidney function, guiding appropriate therapies based on filling pressures., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier B.V.)

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., (© 2022 British Pharmacological Society.)

Background: Current guidelines suggest the use of isotonic saline (IS) infusion as the preferred resuscitation fluid in the management of diabetic ketoacidosis (DKA). However, balanced electrolyte solutions (BES) have been proposed as an alternative due to a lower propensity to cause hyperchloremic metabolic acidosis. Evidence regarding the use of BES in DKA remains limited., Objectives: To determine if the use of BES in fluid resuscitation leads to faster resolution of DKA compared to IS., Methods: The study involves a comprehensive search of literature from PubMed, Cochrane CENTRAL, Google Scholar, and Science Direct of clinical trials addressing the use of BES vs IS in fluid resuscitation in DKA. The time to resolution of DKA was examined as the primary endpoint. Pooled hazard ratios (HR) and Mean Difference (MD) in hours with their 95% confidence intervals (CI) were calculated using a random-effects model., Results: The literature search included 464 studies that were screened individually. A total of 9 studies were identified but 6 studies were excluded due to irrelevance in the outcome of interest and target population. The pooled hazard ratio HR significantly revealed 1.46 [1.10 to 1.94] (p = 0.009) with 12% heterogeneity while MD was -3.02 (95% CI -6.78-0.74; p = 0.12) with heterogeneity of 85%., Conclusion: Considering the evidence from pooled small randomized trials with moderate overall certainty of evidence, the use of BES in DKA was associated with faster rates of DKA resolution compared to IS., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Heart failure (HF) with reduced ejection fraction (HFrEF) has been defined by varying ejection fraction (EF) criteria in clinical trials, leading to differences in quantifying treatment effects., Areas Covered: The definitions of HFrEF in randomized controlled trials from 2010 until 2020 were collected. The EF ranges were clustered into very low (<30%), low (30-39%) and mildly reduced (40-49%) stratified by intervention. A time series regression analysis was performed. A total of 3052 articles were screened and 706 were included. Interventions included were pharmacologic (37%), device therapy (10%), and a combination of programs, procedural, and laboratory testing (53%). Regarding EF cutoffs, 41% of the studies utilized <40% while 26% used <35%. About 31% did not have a clearly defined EF. Between 2010 and 2020, studies with HFrEF ranges 30-39% have significantly decreased (p value < 0.001 for trend), but those which included very low EF (<30%) and mildly reduced EF (40-49%) have remained the same., Expert Opinion: EF definitions across clinical trials in HFrEF varied widely. Defining the specific target HF population phenotype when designing trials or in patient treatment is important as various beneficial effects of different heart failure treatment modalities can be modified or even attenuated across the spectrum of EF.

Background and objective Multiple comorbidities may contribute to high readmission rates post-transplant procedures. In this study, we aimed to assess the rates and factors associated with hospital readmissions for dyspeptic symptoms among transplant patients. Methods This was a retrospective analysis of adult patients who underwent solid organ transplants at our institution. Pregnant patients or those patients with preexisting gastroparesis were excluded from the study. Readmissions associated with the International Classification of Diseases (ICD) codes for nausea/vomiting, weight loss, failure to thrive, abdominal pain, and/or bloating were included. Factors associated with 30-day and frequent readmissions (two or more) were explored. Results A total of 931 patients with solid organ transplants were included; 54% had undergone kidney transplants while 34% were liver transplants. Of note, 30% were readmitted within the first 30 days after discharge following transplant while 32.3% had frequent readmissions. A post-transplant upper endoscopy (EGD) was performed in 34% with food residue discovered in 19% suggesting gastroparesis. However, since only 22% of these patients had a gastric emptying study, only 6% were formally diagnosed with gastroparesis, which was independently associated with both 30-day [odds ratios (OR): 2.58, 95% confidence intervals (CI): 1.42-4.69] and frequent readmissions (OR: 6.71, 95% CI: 3.45-13.10). The presence of pre-transplant diabetes (35%) was significantly associated with a diagnosis of gastroparesis following transplant (OR: 5.17, 95% CI: 2.79-9.57). The use of belatacept (OR: 0.63, 95% CI: 0.42-0.94, p=0.023) was associated with a decrease in the odds of 30-day readmissions. Conclusion A significant number of patients were readmitted due to dyspeptic symptoms after solid organ transplants. Diabetes and gastroparesis were significantly associated with higher odds of readmissions while the use of belatacept appeared to be a protective factor., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Jarrett et al.)

Competing Interests: The authors have no competing interests to declare.

Background: Determination of adequacy of decongestion remains a significant challenge in the management of acute heart failure (AHF)., Methods: This is a prospective single center cohort study of patients (>18 years old) admitted for AHF on intravenous diuretics, with BNP >100 pg/mL or echocardiographic findings of reduced ejection fraction or diastolic dysfunction, and at least 1 clinical sign of volume overload. Patients with eGFR ≤45 mL/min or on dialysis, and with exposure to contrast dye or nephrotoxins were excluded. Serum and spot urine osmolality were obtained in the early morning simultaneously daily for 5 days or until discharge. Receiver operating characteristic curves were used to analyze the optimal cutoffs for the osmolality values in the prediction of heart failure (HF) readmissions Results: Of the total 100 patients, 62% were male and 59% were Black American. The mean age was 64.41 ± 12.53 and 34% had preserved ejection fraction. Patients with 30-day readmission had higher serum osmolality (mOsm/kg) on admission (305 [299-310] vs. 298 [294-303]; p = 0.044) and had higher drop in serum osmolality between admission and discharge (-7.5 [-9.0, -1.25] vs. -1.0 [-4.0, 4.0]; p = 0.044). Serum osmolality on admission of >299 mOsm/kg (sensitivity: 83%, specificity: 61%) and drop in serum osmolality between admission and discharge of >2 mOsm/kg (sensitivity: 83%, specificity: 65%) was associated with 30-day HF readmissions. No patients discharged with urine osmolality more than 500 mOsm/kg had 30-day readmissions, but this was not statistically significant, p = 0.334., Conclusion: Measurement of serum osmolality and urine osmolality may have some utility in AHF, but interpretation should consider baseline values and dynamic changes to account for individual differences in sodium and water handling., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background/ Rationale Clostridioides difficile infection (CDI) is transmitted via the fecal-oral route and is implicated in antibiotic-associated colitis. Similar to CDI, patients with coronavirus disease 2019 (COVID-19) require early identification and isolation, appropriate personal protective equipment, and environmental disinfection to prevent further transmission. In light of this similarity between isolation and protective requirements to prevent transmission of these diseases, we aim to investigate whether there was a decrease in the incidence of CDI during the peak periods of the COVID-19 pandemic compared to historical rates. Methods This is a single-center retrospective analysis of the rates of CDI in our institution. COVID-19 time periods were identified from March 2020 to January 2021 and peak periods (with >50 active patients per day) were defined. The non-COVID-19 periods were July 2017 to February 2020. Rates of CDI were also directly compared across the yearly time period. CDI rates were presented in a per 1000 patient days format. Rates were analyzed per year and during the COVID-19 peaks at our institution. Mann-Whitney U test was used to compare rates between two time periods, while differences across multiple time intervals were analyzed using the Kruskal-Wallis test. Results The median (interquartile range [IQR]) of CDI rates of infection per 1000 patient days for the non-COVID time period from July 2017 to February 2020 was 0.34 (0.23-0.45) while COVID time periods had higher 0.44 (0.25-0.51) rates of CDI although this was not statistically significant (p=0.224). However, there was a statistically significant difference (p=0.036) with COVID peak periods having higher rates of CDI 0.49(0.39-0.74) vs 0.34(0.23-0.44). Overall, there was no statistically significant difference in the rates of CDI across years or time periods (p=0.396). Discussion/Conclusion There was no difference in the rates of hospital-acquired CDI between COVID-19 and non-COVID-19 time periods at our institution., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Yadlapati et al.)

Background: Given the heterogeneity of etiologies, pathophysiology, and presentation of angioedema, variations in clinical outcomes, such as intubation and hospital readmissions, need further clarification., Objective: To determine the factors associated with intubation and hospital readmissions in patients with angioedema., Methods: Retrospective study of patients evaluated with a diagnosis of angioedema in a 6-year period. Demographic and clinical data, such as medication use, family history, comorbidities, and symptoms, were recorded. Multivariable logistic regression was used to analyze factors associated with intubation, whereas Cox regression was used to analyze readmissions., Results: Of 636 patients, the most common cause of angioedema was that induced by angiotensin-converting enzyme inhibitor (ACEI) at 58%. The overall mortality was 0.5%. After adjusting for sex, race, comorbidities, and type of angioedema, smoking (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.10-2.93; P = .02), calcium channel blocker therapy (OR, 1.91; 95% CI, 1.18-3.10; P = .009), histaminergic symptoms (OR, 3.21; 95% CI, 1.93-5.33; P < .001), and age (OR, 1.02; 95% CI, 1.00-1.04; P = .02) were independently associated with increased odds of intubation. Involvement of either the pharynx, larynx, or tongue was associated with higher odds of intubation (OR, 20.96; 95% CI, 10.63-41.33; P < .001). A total of 10% of the patients had a readmission for angioedema within 90 days, and 75% occurred within 30 days. After multivariable Cox regression analysis, only chronic obstructive pulmonary disease and asthma (OR, 2.13; 95% CI, 1.12-4.07; P = .02) and ACEI-related angioedema (OR, 2.93; 95% CI, 1.33-6.47; P = .008) were significantly associated with readmissions., Conclusion: Smoking, calcium channel blocker use, histaminergic symptoms, age, and upper airway involvement were markedly associated with intubation. The presence of chronic obstructive pulmonary disease, asthma and ACEI-related angioedema were independently associated with increased odds of readmission., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Direct oral anticoagulants (DOAC) off-label use data is lacking. Our study aimed to assess the clinical outcomes in a racially mixed population treated for atrial fibrillation (AF) and venous thromboembolism (VTE)., Methods: We retrospectively evaluated six months of DOAC prescriptions for AF or VTE treatment. Prescriptions were classified as off-label or appropriate following FDA labeling. The off-label group was sub-classified as under or overdosing., Results: Of the 1,087 DOAC prescriptions, 67% were for AF. African Americans and Caucasians were equally represented. There were 171 (16%) inappropriate prescriptions, with 106 (62%), being underdosed. The off-label group had a higher 30-day readmissions risk (OR = 1.69, 95% CI:1.11-2.54, p = 0.012) and 1-year all-cause mortality (OR = 1.90, 95% CI:1.02-3.37, p = 0.032). There was no difference in major bleeding (OR = 1.27, 95% CI:0.63-2.37, p = 0.480) or new thromboembolism (OR = 1.27, 95% CI:0.73-2.13, p = 0.369) between the groups. Underdosing carried a higher risk of new thromboembolism (OR = 3.15, 95% CI:1.09-9.15, p = 0.024)., Conclusions: One in every six patients received off-label DOACs dosing. Off-label use had increased 30-day readmissions and 1-year all-cause mortality. Underdosing was associated with a higher risk of new thromboembolism.

Background: Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin-receptor blocker (ARB) are cornerstones in the treatment of heart failure with reduced ejection (HFrEF). However, there are limited data on their risk-benefit profile in patients with acute heart failure requiring hospitalizations., Methods: We did a meta-analysis pooling data from all studies examining the use of ACEi/ARB in patients hospitalized for heart failure compared to patients without ACEi/ARB use. We calculated pooled hazard ratios (HR) and their 95% confidence intervals (CI) using a random-effects model., Results: Twenty-five studies were included in the meta-analysis. Continued use of ACEi/ARBs in hospitalized patients with HFrEF was associated with lower 1-year mortality risk (pooled HR 0.68 [0.60-0.77] p < 0.001) and with lower 1-6-year mortality risk in those with heart failure preserved ejection fraction (HFpEF) (pooled HR 0.86 [0.78-0.94] p = 0.002). There were significant reductions in 1-year HF readmissions among hospitalized HFrEF patients (pooled HR 0.83 [0.73-0.95] p = 0.005)., Conclusion: Maintaining or initiating patients with HFrEF hospitalized for acute decompensated heart failure (ADHF) on ACEi/ARB is associated with a reduce risk of mortality and 1-year admissions, but the effect size is lower among those with HFpEF with more heterogeneous outcomes.