In-hospital mortality of heparin-induced thrombocytopenia in end-stage kidney disease. A retrospective national population-based cohort study.

AIM: Heparin induced thrombocytopenia (HIT) and end stage kidney disease (ESKD) are independent conditions associated with increased mortality and morbidity, however, whether ESKD is an independent risk factor for increased mortality in HIT admissions is not well studied. Therefore, we aimed to compare in-hospital mortality in HIT admissions based on their ESKD status. METHODS: This is a retrospective cohort study of HIT hospitalizations aged 18 and older using the 2016-2019 national inpatient sample (NIS) database. RESULTS: From 2016 to 2019 we had 12 161 admissions for HIT among 28 484 087 total hospitalizations. The annual incidence rate for HIT admissions per 100 000 admissions were: 47, 46, 41.1, and 36.6, respectively (p < .001) in 2016, 2017, 2018, and 2019 respectively. Among HIT admissions, the mean age was 64.3 years, 46.8% were females, 68% were Whites and 16% were Blacks. Black patients have a significantly higher likelihood of in-hospital mortality than White patients (aOR 1.25; 95% CI: 1.06, 1.48; p = .007). Patients who did not have any insurance or self-pay had higher mortality compared to Medicare (aOR 1.64; 95% CI: 1.13, 2.38; p = .009). ESKD status was not associated with higher or lower in-hospital mortality among HIT admissions (aOR 1.002; 95% CI: 0.84, 1.19; p = .981) after adjusting for age, sex, race, and insurance status. CONCLUSION: There are no higher or lower odds of in-hospital mortality in the ESKD subgroup in HIT admissions in adults. Decreasing incidence of HIT hospitalizations was seen over the years from 2016 to 2019.

All-cause and in-hospital mortality after aspirin use in patients hospitalized with COVID-19: a systematic review and meta-analysis.

Background: With the results of the largest randomized controlled trial (RECOVERY) and the most extensive retrospective cohort study on coronavirus disease 2019 (COVID-19) recently published, we performed a meta-analysis on the association of aspirin with mortality of COVID-19. We aimed to investigate the role of aspirin in COVID-19 hospitalizations. Materials and Methods: We searched PubMed, EMBASE and Cochrane databases for studies from 1 January 2020 until 20 July 2022, that compared aspirin versus non-aspirin use in hospitalized COVID-19 patients. We excluded case reports, review articles and studies on non-hospitalized COVID-19 infections. We used the inverse variance method and random effects model to pool the individual studies. Results: Ten observational studies and one randomized controlled trial met the criteria for inclusion. There were 136 695 total patients, of which 27 168 were in the aspirin group and 109 527 were in the non-aspirin group. Aspirin use was associated with a 14% decrease in all-cause mortality compared with non-aspirin use in patients hospitalized with COVID-19 [relative risk (RR) 0.86, confidence interval (95% CI) 0.76-0.97; P = 0.002; I 2 =64%]. Among subgroups of studies reporting in-hospital mortality in COVID-19 hospitalizations, aspirin use was associated with a 16% decrease in in-hospital mortality compared with non-aspirin use (RR 0.84, 95% CI 0.71-0.99; P = 0.007; I 2 =64%). Conclusion: Our study shows that aspirin decreases in-hospital mortality in patients hospitalized with COVID-19. Further studies are needed to assess which COVID-19 patient populations benefit most, such as patients on aspirin for primary versus secondary prevention of atherosclerotic disease. In addition, significant bleeding also needs to be considered when assessing the risk-benefit of aspirin use.

Meta-analysis examining phosphodiesterase-5 inhibitors in heart failure with preserved ejection fraction.

Patients with heart failure with preserved ejection fraction have reduced cyclic guanosine 3',5'-monophosphate (cGMP) levels compared to those with reduced ejection fraction. Phosphodiesterase-5 inhibitors may play a cardioprotective role by potentiating the cGMP pathway. To address this question, we conducted a systematic search for randomized trials using the electronic databases of PubMed, Embase, and Google Scholar and used RevMan (version 5.4) for the data analysis. We included 221 subjects in the phosphodiesterase group (mean age 69.2 ± 3.43 years; 58.82% male) and 202 subjects in the control group (mean age 70.4 ± 4.96 years; 53.46% male). The mean follow-up duration was 5.85 ± 3.43 months. The pooled results showed no significant differences in peak oxygen consumption, 6-minute walking distance, mitral annular E/e' ratio, left ventricular ejection fraction, mean pulmonary artery pressure, pulmonary artery systolic pressure, and pulmonary vascular resistance between the phosphodiesterase group and the control group.

The efficacy and safety of roxadustat for the treatment of anemia in non-dialysis dependent chronic kidney disease patients: An updated systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Roxadustat (ROX) is a new medication for anemia as a complication of chronic kidney disease (CKD). Our meta-analysis aims to evaluate the efficacy and safety of ROX, especially on the cardiovascular risks, for anemia in NDD-CKD patients. METHODS: Electronic databases were searched systematically from inception to July 2021 to look for randomized control trials (RCTs) that evaluated ROX NDD-CKD patients. Hemoglobin level and iron utilization parameters, including ferritin, serum iron, transferrin saturation (TSAT), total iron-binding capacity (TIBC), transferrin, and hepcidin were analyzed for efficacy. Pooled risk ratios (RRs) and standardized mean differences (SMDs) were calculated and presented with their 95% confidential intervals (CIs). RESULTS: Nine RCTs included a total of 3,175 patients in the ROX group and 2,446 patients in the control group. When compared the control group, ROX increased Hb level significantly (SMD: 1.65; 95% CI: 1.08, 2.22; P< 0.00001) and improved iron utilization parameters by decreasing ferritin (SMD: -0.32; 95% CI: -0.51, -0.14; P = 0.0006), TSAT (SMD: -0.19; 95% CI: -0.32, -0.07; P = 0.003), and hepcidin (SMD: -0.74; 95% CI: -1.09, -0.39; P< 0.0001) and increasing TIBC (SMD: 0.99; 95% CI: 0.76, 1.22; P< 0.00001) and transferrin (SMD: 1.20; 95% CI: 0.70, 1.71; P< 0.00001). As for safety, ROX was associated with higher serious adverse effects (RR: 1.07; 95% CI: 1.01, 1.13; P = 0.01), deep venous thrombosis (DVT) (RR: 3.80; 95% CI: 1.5, 9.64; P = 0.08), and hypertension (HTN) (RR: 1.37; 95% CI: 1.13, 1.65; P = 0.001). CONCLUSION: We concluded that ROX increased Hb level and improved iron utilization parameters in NDD-CKD patients, but ROX was associated with higher serious adverse effects, especially DVT and HTN. Our results support the use of ROX for NDD-CKD patients with anemia. However, higher-quality RCTs are still needed to ensure its safety and risk of thrombosis.

Meta-analysis comparing dexmedetomidine versus standard of care for sedation in patients with sepsis.

We aimed to evaluate the clinical benefits of dexmedetomidine (DEX) in comparison with the standard of care (SOC) sedation in critically ill, septic patients. Electronic databases (PubMed, EMBASE, Cochrane Central, Scopus, and Google Scholar) were systematically searched to identify only randomized clinical trials performed up until February 12, 2021. The primary outcomes were 28-day mortality, 90-day mortality, and intensive care unit (ICU) length of stay (LOS). We calculated risk ratios (RRs), 95% confidence intervals (CIs) for dichotomous data, and weighted mean differences (WMDs) for continuous data using a random-effects model. Seven randomized clinical trials were included, with a total of 529 patients in the DEX group and 520 patients in the SOC group. Compared with SOC, DEX was associated with a nonstatistically significant reduced 28-day mortality (RR = 0.76; 95% CI [0.51, 1.14]; P = 0.19), 90-day mortality (RR = 0.94; 95% CI [0.75, 1.18]; P = 0.60), and ICU LOS (WMD = -0.85; 95% CI [-2.60, 0.90]; P = 0.34). We conclude that among septic patients on sedation, the use of DEX in the ICU demonstrated no significant difference from SOC sedation protocols with respect to 28-day mortality, 90-day mortality, and total ICU LOS. Our findings suggest that DEX does not confer clinical benefit over SOC sedation in critically ill patients with sepsis.

The Effect of Vasopressin and Methylprednisolone on Return of Spontaneous Circulation in Patients with In-Hospital Cardiac Arrest: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Cardiac arrest is often fatal if not treated immediately by cardiopulmonary resuscitation to restore a normal heart rhythm and spontaneous circulation. We aim to evaluate the clinical benefits of vasopressin and methylprednisolone versus placebo for patients with in-hospital cardiac arrest. DATA SOURCES: We searched PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar from inception to October 17, 2021, by using search terms included "Vasopressin" AND "Methylprednisolone" AND "Cardiac arrest". STUDY SELECTION AND DATA EXTRACTION: We included randomized controlled trials (RCTs) that compared vasopressin and methylprednisolone to placebo. The main outcomes were the return of spontaneous circulation (ROSC) and survival to hospital discharge. DATA SYNTHESIS: A total of three RCTs, with a total of 869 patients, were included. The pooled risk ratios (RRs) were calculated along with their 95% confidence intervals (CIs). Our result showed an increase in ROSC in patients who received vasopressin and methylprednisolone (RR = 1.32; 95% CI = [1.18, 1.47], p < 0.00001) when compared with the placebo group. However, there was no difference between both groups regarding survival to hospital discharge (RR = 1.76; 95% CI = [0.68, 4.56], p= 0.25). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The current guidelines recommend epinephrine for patients with in-hospital cardiac arrest. Our meta-analysis updates clinicians about using vasopressin and methylprednisolone besides epinephrine, providing them with the best available evidence in managing patients with in-hospital cardiac arrest. CONCLUSION: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone besides epinephrine is associated with increased ROSC compared with placebo and epinephrine. However, high-quality RCTs are necessary before drawing a firm conclusion regarding the efficacy of vasopressin and methylprednisolone for patients with in-hospital cardiac arrest.

Hypothyroidism Is Associated With Longer Hospital Stay Following Implantation Of Left Ventricular Assist Device.

BACKGROUND: There has been a steady and consistent rise in the use of left ventricular assist devices in the management of patients with advanced heart failure. Hypothyroidism also remains one of the most common endocrine conditions with a significant impact on the development and overall outcomes of heart failure. The authors analyzed the National Inpatient Sample to evaluate the effect of hypothyroidism on the in-hospital outcomes of patients with end-stage heart failure following the placement of left ventricular assist device. METHODS: The national inpatient sample was queried to identify all adult patients who had LVAD placement from 2004 to 2014. They were subsequently divided into those with hypothyroidism and those without hypothyroidism. The primary outcome was in-hospital mortality. Other outcomes were acute kidney injury, length, and cost of hospitalization. Logistic regression models were created to determine the outcomes of interest. RESULTS: Of 2643 patients in the study, 5.4% had hypothyroidism, and 94.6% did not. The hypothyroid patients were significantly older compared to the non-hypothyroid patients (mean age 58.6 years vs 49.95 years, P-value <.0001). Both groups had similar gender composition. In-hospital mortality was similar across both groups. However, there was a higher incidence of acute kidney injury (AKI) in the hypothyroid group (adjusted odds ratio [aOR 1.83, P-value <.001]). Hypothyroid patients had longer hospital stays (adjusted mean difference [aMD] 5.19, P-value .0001). Hospital charges were also higher in the hypothyroid group. CONCLUSION: This study found that LVAD is associated with longer hospital stay in hypothyroid patients with heart failure.

Ipilimumab and Nivolumab induced ventricular tachycardia in a patient with metastatic renal cell carcinoma.

The immune checkpoint inhibitor (ICIs) as Nivolumab and Ipilimumab is a novel class of medication used in the management of several metastatic malignancies. ICIs can cause immune-related adverse events due to autoreactive T cell activation. Cardiovascular complications comprised myocarditis, conduction abnormalities, ventricular storm, and cardiomyopathy. Cardiomyopathy is one of the significant side effects highlighted in some of the case reports. The physicians should include autoimmune toxicities as the potential differential diagnosis in patients presenting with an unusual presentation and receiving ICIs. We report a case of a 66-year-old female with advanced renal cell carcinoma who developed cardiomyopathy and ventricular tachycardia from nivolumab and ipilimumab therapy.

Cancer-Related Non-Bacterial Thrombotic Endocarditis Presenting as Acute Ischemic Stroke.

Non-bacterial thrombotic endocarditis (NBTE), also known as marantic endocarditis, is a rare form of noninfectious endocarditis presenting with thromboembolism including ischemic cerebral stroke. It is mostly associated with advanced malignancy and characterized by the presence of sterile vegetation on heart valves. The diagnosis is usually based on vegetations seen on an echocardiogram, with negative blood cultures suggesting a noninfectious etiology. The treatment for this condition includes systemic anticoagulation. In this report, we discuss the case of a 61-year-old Caucasian female who presented to our facility with an ischemic stroke. She was found to have vegetations on the mitral valve with negative blood cultures. Further studies revealed metastatic pancreatic cancer. The patient's condition improved following in-hospital management, and she was discharged home for outpatient follow-up and treatment. Through this report, we highlight the importance of considering a search for malignancy in patients presenting with these clinical features. Early diagnosis and prompt management are critical to reduce the complications of NBTE and improve the patients' quality of life.

Systematic Review and Meta-Analysis: Can We Compare Direct Oral Anticoagulants to Warfarin in Patients With Atrial Fibrillation and Bio-Prosthetic Valves?

Background There are no clear consensus guidelines on the indications and types of anticoagulation therapies in patients with bio-prosthetic valves either with concomitant atrial fibrillation (AF) or sinus rhythm. In our meta-analysis, we assessed the safety and efficacy of DOACs as compared to the standard treatment with warfarin in patients with AF and bioprosthetic valves. Methods We included randomized controlled trials (RCTs), cohort studies in the English language, and studies reporting patients with valvular heart disease that included bioprosthetic valvular disease. A systematic literature review using Embase, PubMed, and Web of Science was performed using the terms "Direct Acting Oral Anticoagulant," "Oral Anticoagulants," "Non-Vitamin K Antagonist Oral Anticoagulant," "Atrial Fibrillation," "Bioprosthetic Valve" for literature published prior to January 2021. Extraction of data from included studies was carried out independently by three reviewers from Covidence. We assessed the methodical rigor of the included studies using the modified Downs and Black checklist. Results Four RCTs and one observational study (n=1776) were included in our study. A random-effect model using RevMan (version 5.4; The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen) was used for data analysis. The pooled data showed that there was a non-significant reduction in the incidence of stroke and systemic embolism in the patients taking DOACs as compared to warfarin (HR 0.69; 95% CI, 0.29, 1.67; I2 = 50%). The incidence of major bleeding was lower in the DOACs group; the difference was statistically significant (HR 0.42; 95% CI, 0.26, 0.67; I2 = 7%). The difference was not statistically significant for all-cause mortality in both groups (HR 1.24; 95% CI, 0.91, 1.67; I2 = 0%). Conclusion Our results showed that there was no difference in the outcomes of stroke and systemic embolism between DOACs and warfarin but there were statistically significantly lower major bleeding events. We conclude that larger clinical trials are needed to assess the true safety and efficacy of DOACs in patients with AF and bioprosthetic valves.

Pharmacotherapies in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) causes significant cardiovascular morbidity and mortality. It is a growing problem in the developed world, especially, in the aging population. There is a paucity of data on the treatment of patients with HFpEF. We aimed to identify pharmacotherapies that improve peak oxygen consumption (peak VO2), cardiovascular mortality, and HF hospitalizations in patients with HFpEF. METHODS: We conducted a systematic literature search for English studies in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and Google scholar. We searched databases using terms relating to or describing HFpEF, stage C HFpEF, and diastolic HF and included only randomized controlled trials (RCTs). RevMan 5.4 (The Cochrane Collaboration, 2020, London, UK) was used for data analysis, and two independent investigators performed literature retrieval and data-extraction. We used PRISMA guidelines to report the outcomes. We included 14 articles in our systematic review and six studies in meta-analysis. RESULTS: We calculated the pooled mean difference (MD) of peak VO2 between placebo and pharmacotherapies. Our meta-analysis showed that the peak VO2 was comparable between pharmacotherapies and placebo in HFpEF (MD = 0.09, 95% CI: -0.11, 0.30, I2 =28%). Our systematic review highlights that statins and spironolactone use should be further studied in larger RCTs due to their potential beneficial effect on all-cause mortality and hospitalizations, respectively. CONCLUSION: Compared to placebo, none of the pharmacotherapies significantly improved peak VO2 in HFpEF except ivabradine. In our meta-analysis, the pooled improvement in peak VO2 is non-significant. This needs validation with larger studies. We are lacking larger studies on pharmacotherapies that improve peak VO2 in HFpEF. Statin and spironolactone should be further studied in patients with HFpEF as few trials have shown improvement in all-cause mortality and reduction in HF hospitalizations in selected patients, respectively.

The efficacy of Roxadustat for the treatment of anemia in dialysis dependent chronic kidney disease patients: an updated systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Anemia is a common complication in chronic kidney disease (CKD) with increased morbidity and mortality. Recently published RCTs were conducted to compare the effect of the new medication roxadustat (ROX) with erythropoiesis-stimulating agent (ESA) in dialysis-dependent CKD (DD-CKD) patients. Our article aimed to meta-analyze published RCTs to investigate the efficacy and safety of ROX for anemia in DD-CKD patients and update the effect of the new studies on overall analysis with subsequent impact on management. METHODS: Electronic databases (PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar) were searched systematically from inception to July 2021 by using this search term (Roxadustat OR ASP1517 OR FG4592 OR "FG-4592") AND (kidney OR renal) AND (Anemia). We only included randomized control trials (RCTs) that reported the primary outcome of change in hemoglobin (Hb) level and iron utilization parameters, including ferritin, serum iron, TSAT, TIBC, transferrin, and hepcidin. RESULTS: Ten RCTs were finally included with 3031 patients in the ROX group and 2737 patients in the control group. ROX was associated with increase in Hb level (SMD: 0.2; 95% CI: 0.02, 0.39; P=0.03), TIBC (SMD: 0.79; 95% CI: 0.61, 0.98; P<0.00001), serum iron (SMD: 0.27; 95% CI: 0.18, 0.36; P<0.00001), transferrin (SMD: 0.98; 95% CI: 0.81, 1.15; P<0.00001) and decrease in hepcidin (SMD: -15.53; 95% CI: -28.07, -3.00; P<0.02) when compared with control group. There was no difference between ROX and the control group regarding ferritin level and TSAT. Sensitivity analysis by removing the most recent studies, Chen et al. or Hou et al. did not show significant difference in regard to change in Hb level. There was no difference between both groups regarding the serious side effects. However, ROX showed higher TEAEs when compared to the control group (RR: 1.03; 95% CI: 1.01, 1.05; P=0.002). DISCUSSION: Our updated meta-analysis concluded that ROX increased Hb level and improved iron utilization parameters in DD-CKD patients, but ROX was associated with higher TEAEs. Our results support the use of ROX for DD-CKD patients with anemia. However, higher-quality RCTs are still needed to confirm the results of our review.