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.

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.

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.

Dialysis access as a source of infective endocarditis in dialysis patients.

The incidence of Infective Endocarditis (IE) is higher in dialysis patients compared to the general population. A major risk factor for IE in this group stems from bacterial invasion during repeated vascular access. Previous studies have shown increased risk of bacteremia in patients with indwelling dialysis catheters compared to permanent vascular access. However, association between the development of IE and the type of dialysis access is unclear. We aimed to examine the associated types of intravascular access and route of infection in dialysis patients who were admitted with infective endocarditis at our center. All patients admitted to Albert Einstein Medical Center in Philadelphia with a diagnosis of infective endocarditis who were on chronic hemodialysis were identified from the hospital database for the period of 1/1/07 to 12/31/18. Modified Duke criteria was used to confirm the diagnosis of infective endocarditis. A total of 96 cases were identified. Of those, 57 patients had an indwelling dialysis catheter while the other 39 had permanent dialysis access. In 82% of patients with dialysis catheters, their dialysis access site was identified as the primary source of infection compared to 30% in those with permanent dialysis access (p<0.001). The number of dialysis catheters placed in the preceding 6 months was strongly associated with endocarditis resulting from the dialysis access site (OR = 3.202, p=0.025). Dialysis catheters are more likely to serve as the source of infection in dialysis patients developing IE compared to permanent dialysis access. Increased awareness of risk of IE associated with dialysis catheters is warranted.

Gastric Lipomas: A Case Series and Review of the Literature.

Introduction: The purpose of this case series was to review a rare subset of tumors known as gastric lipomas, which are typically found incidentally. The motivation for this study arose from the identification of 2 cases within our institution in a short period. Case Presentation: The study involved a review of the diagnosis and management of 2 patients presenting with gastric lipomas at our institution after symptoms of gastrointestinal bleeding. With the advent of new radiologic investigations such as computed tomography and magnetic resonance imaging and advances in endoscopy, there are new approaches to identifying and managing these tumors. On further evaluation of the literature, we found that despite the availability of minimally invasive endoscopic techniques such as mucosal resection and submucosal dissection in the setting of large tumors, most patients tend to have to resort to surgical management. Conclusion: This case series underscores the rarity of gastric lipomas and their often-incidental discovery. Further investigation into endoscopic approaches for managing these tumors is needed, and additionally, there is a need to explore a potential association between gastric lipomas and malignancy, as chronic inflammation of the overlying mucosa may play a significant role.

Nausea, Vomiting, and Dyspepsia Following Solid Organ Abdominal Transplant.

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.

Examining the Rate of Clostridioides (Formerly Clostridium) Difficile Infection Pre- and Post-COVID-19 Pandemic: An Institutional Review.

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.

Prognostic Value of Left Ventricular Global Strain Analysis by Two-Dimensional Speckle-Tracking Echocardiography in Non-Hemodynamically Significant Intermediate Coronary Lesions.

Intermediate coronary lesions represent a major challenge for the invasive and noninvasive cardiologist. Left ventricular strain calculation by speckle tracking echocardiography has the capacity to analyze the motion of the cardiac tissue. This study aimed to evaluate its usefulness and prognostic significance in nonhemodynamically significant intermediate coronary lesions. We studied 247 patients who underwent a clinically indicated coronary angiogram. Each of the patients had a single nonrevascularized nonhemodynamically significant intermediate severity coronary lesion (ISCL) with a fractional flow reserve greater than 0.80. The left ventricular global longitudinal strain (GLS) was calculated using speckle-tracking echocardiography with TomTec 2D Cardiac Performance Analysis (Unterschleissheim, Germany). An abnormal GLS was defined as less than -20%. The primary endpoints were revascularization of the target lesion, admissions for major adverse cardiac events (MACE), and cardiac-related mortality, all within 2 years. On multivariate logistic regression data analysis, we found that patients with an ISCL and abnormal GLS had an increased risk for admissions due to MACE (odds ratio [OR] 1.06, P < 0.05, confidence interval [CI] 95%, 1.005-1.120], and an increased risk of cardiac-related death (OR 1.12, P < 0.05, CI 95% 1.012-1.275). There was no difference in the need for target lesion revascularization among individuals with normal and abnormal GLS (1.00, P 0.88, CI 95% .950-1.061). Left ventricular strain analysis by speckle-tracking echocardiography showed an independent prognostic value in patients with nonrevascularized nonhemodynamically significant coronary lesions.

Comparison of Patient Clinical characteristics and Outcomes Between Different COVID-19 Peak Periods: A Single Center Retrospective Propensity Matched Analysis.

Introduction While Coronavirus disease 2019 (COVID-19) specific treatments have been instituted, overall mortality rates among hospitalized patients remain significant. Our study aimed to evaluate patient clinical characteristics and outcomes comparing the different COVID-19 infection peak periods. Methods This is a retrospective study of all adult patients hospitalized with a confirmed diagnosis of COVID-19 between March 1 to April 24, 2020 and November 1 to December 31, 2020, which corresponded to the first and second waves of COVID-19 infection in our institution, respectively. Demographic and clinical characteristics of the patients were compared and used for propensity matching. Clinical outcomes, such as need for intubation, renal replacement therapy and inpatient mortality were subsequently compared between the two groups. Results Patients in the second COVID-19 wave had a significantly higher body mass index (32.58 vs 29.83, p <0.001), as well as prevalence of asthma (14% vs 8%, p=0.019) and chronic kidney disease (42% vs 18%, p <0.001). Almost all patients in the second COVID-19 wave received corticosteroid treatment (99% vs 30%, p <0.001), and significantly more patients received remdesivir (43% vs 2%, p <0.001). Meanwhile, none of the patients in the second COVID-19 wave were treated with tocilizumab or hydroxychloroquine. Differences in clinical outcomes, such as need for renal replacement therapy or intubation, and median length of stay were not statistically significant. Inpatient mortality remained largely unchanged between the two COVID-19 peak periods. Discussion/ Conclusion In our institution, after propensity matched analysis, clinical outcomes such as need for renal replacement therapy, intubation and inpatient mortality remained unchanged between the two COVID-19 peak periods.

Off-label direct oral anticoagulants dosing in atrial fibrillation and venous thromboembolism is associated with higher mortality.

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.

National trends in hospitalizations and outcomes in patients with alcoholic cardiomyopathy.

BACKGROUND: Numerous studies have shown conflicting results regarding the natural history and outcomes with alcoholic cardiomyopathy (AC). HYPOTHESIS: Determining the trends in hospitalization among patients with AC and associated outcomes will facilitate a better understanding of this disease. METHODS: We conducted our analysis on discharge data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) from 2002 through 2014. We obtained data from patients aged ≥18 years with diagnosis of "Alcoholic Cardiomyopathy." Death was defined within the NIS as in-hospital mortality. By using International Classification of Disease-9th edition-Clinical Modification (ICD-9CM) diagnoses and diagnosis-related groups different comorbidities were identified. RESULTS: We studied a total of 45 365 admissions among patients with AC. The absolute number of admissions decreased from 2002 to 2014 (3866-2834 admissions). In-hospital mortality was variable throughout study duration without a clinically relevant trend (Mean 4.5%, range 3.6%-5.6%). The patients were mostly male (87%) and Caucasian (50.5%). Commonest age groups involved were 45-59 years (46.7%) followed by 60-74 years (29.2%). Trends in associated comorbidities such as smoking, drug abuse, depression, and hypertension increased over the same time period. Among all admissions, almost half were for cardiovascular etiologies (48.9%) and heart failure (≈24%) was the commonest reason for hospital admission. CONCLUSION: While the overall admissions among patients with AC decreased over time, the proportion of patients with high-risk characteristics such as smoking, depression, and drug abuse increased. Patients aged 45 and older were largely affected and cardiovascular etiologies predominated among causes for admission.