Curative Pericardiectomy in Interpheron-Resistant Severe Pericardial Erdheim-Chester Disease.

Erdheim-Chester disease is a rare clonal non-Langerhans cell histiocytosis with multisystemic involvement. It affects bones, large vessels, and retroperitoneum. Cardiac involvement is one of the main mortality predictors.1 We present an unusual case that debuted with cardiac tamponade and pericardial constriction requiring pericardiectomy for definitive control. (Level of Difficulty: Intermediate.).

Impact of intra-abdominal pressure on early kidney transplant outcomes.

Increased intra-abdominal pressure (IAP) is common among post-surgical patients and may cause organ dysfunction. However, its impact after kidney transplantation on early postoperative complications and graft recovery remains unclear. We designed a prospective, observational cohort study to describe the prevalence and determinants of IAP, as well as its effect on delayed graft function, postoperative complications, and graft recovery. IAP was measured in 205 kidney transplant recipients every 8 h during the first 72 h after surgery using the urinary bladder technique. Intra-abdominal hypertension was defined as IAP ≥ 12 mmHg. Patients were followed for 6 months or until graft failure/death. Mean IAP was 12 ± 3.3 mmHg within the first 24 h. 78% of subjects presented with intra-abdominal hypertension during the first 72 h. Increased IAP was associated with higher renal resistive index [r = 0.213; P = 0.003] and lower urine output [r = - 0.237; P < 0.001]. 72 h mean IAP was an independent risk factor for delayed graft function [OR: 1.31; 95% CI: 1.13-1.51], postoperative complications [OR: 1.17; 95% CI: 1.03-1.33], and absence of graft function recovery [HR for graft function recovery: 0.94; 95% CI: 0.88-0.99]. Increased IAP was highly prevalent after transplantation and was independently associated with delayed graft function, postoperative complications, and absence of graft function recovery. Routine IAP monitoring should be considered post-transplantation to facilitate early recognition of relevant complications.

Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients.

BACKGROUND: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. PATIENTS/METHODS: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. RESULTS: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). CONCLUSIONS: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.

Impact of Tricuspid Regurgitation Severity and Repair on Aortic Valve Replacement.

BACKGROUND: Aortic stenosis is one of the most prevalent valve diseases but is rarely accompanied by tricuspid regurgitation. Our objective was to analyze the impact of tricuspid regurgitation severity and its surgical treatment on prognosis of patients undergoing aortic valve replacement. METHODS: This was a retrospective cohort study including all patients presenting with aortic stenosis with some degree of tricuspid regurgitation between 2001 and 2018. Patients were grouped according to the degree of tricuspid regurgitation. RESULTS: From a sample of 8080 patients with aortic stenosis, 143 (1.8%) presented with more than trace tricuspid regurgitation. Among patients with mild, moderate, or severe tricuspid regurgitation, we observed no differences in 30-day (15.1% vs 14.8% vs 8.7%; P = .727), 12-month (51.2% vs 56% vs 55%; P = .892), or 5-year (64% vs 73.3% vs 66.7%; P = .798) survival. Aortic valve replacement plus tricuspid annuloplasty, when compared with aortic valve replacement only was associated with longer intensive care unit stay (9 vs 3 days; P = .043) but not higher 30-day (0% vs 15.5%; P = .112), 12-month (38.5% vs 54.3%; P = .278), or 5-year mortality (57.1% vs 67.1%; P = .594). Only history of liver disease and postoperative major morbidity were independent predictors of survival 30 days, 12 months and 5 years after surgery. CONCLUSIONS: Severity of tricuspid regurgitation in patients with aortic stenosis was not associated with increased mortality. Tricuspid annuloplasty did not improve survival in this subset of patients but was associated with increased postoperative morbidity.

Impact of the Economic Crisis on Endocarditis Mortality in Spain: A Nationwide Study.

Economic recession has dire consequences on overall health. None have explored the impact of economic crisis (EC) on infective endocarditis (IE) mortality. We conducted a retrospective, nationwide, temporal trend study analyzing mortality trends by age, sex, and adverse outcomes in patients diagnosed with IE in Spain from 1997 to 2014. Data were divided into two subperiods: pre-EC (January 1997-August 2008) and post-EC (September 2008-December 2014). A total of 25 952 patients presented with IE. The incidence increased from 301.4 to 365.1 per 10 000 000 habitants, and the mortality rate rose from 24.3% to 28.4%. Those aged >75 years experienced more adverse outcomes. Complications due to sepsis, shock, acute kidney injury requiring dialysis, and heart failure increased after the EC onset, and expenditures soared to €16 216. Expenditure per community was related to mortality (P < .001). The EC resulted as an independent predictor for mortality (hazard ratio 1.06; 95% confidence interval 1.01-1.11). Incidence and mortality rate in patients with IE after the onset of the EC have increased as a result of rising adverse outcomes despite an overall increased investment.

Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials.

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., ß-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA <0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5-5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ >5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8-25.2 g/day (SUCRA = 0.94) and patiromer 8.4-16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430.

A randomized prospective multicenter trial for stroke prevention by prophylactic surgical closure of the left atrial appendage in patients undergoing bioprosthetic aortic valve surgery--LAA-CLOSURE trial protocol.

Patients undergoing surgical aortic valve replacement (SAVR) are at high risk for atrial fibrillation (AF) and stroke after surgery. There is an unmet clinical need to improve stroke prevention in this patient population. The LAA-CLOSURE trial aims to assess the efficacy and safety of prophylactic surgical closure of the left atrial appendage for stroke and cardiovascular death prevention in patients undergoing bioprosthetic SAVR. This randomized, open-label, prospective multicenter trial will enroll 1,040 patients at 13 European sites. The primary endpoint is a composite of cardiovascular mortality, stroke and systemic embolism at 5 years. Secondary endpoints include cardiovascular mortality, stroke, systemic embolism, bleed fulfilling academic research consortium (BARC) criteria, hospitalization for decompensated heart failure and health economic evaluation. Sample size is based on 30% risk reduction in time to event analysis of primary endpoint. Prespecified reports include 30-day safety analysis focusing on AF occurrence and short-term outcomes and interim analyses at 1 and 3 years for primary and secondary outcomes. Additionally, substudies will be performed on the completeness of the closure using transesophageal echocardiography/cardiac computed tomography and long-term ECG recording at one year after the operation.

Outcomes of COVID-19 Among Hospitalized Patients With Non-dialysis CKD.

Background: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Corona Virus 2 has generated significant impact on global health worldwide. COVID-19 can cause pneumonia and organ injury. Chronic kidney disease (CKD) has been associated with increased mortality in previous epidemics, but there is a paucity of data regarding actual risks for non-dialysis CKD patients with COVID-19. Methods: Multicenter, observational cohort study including 136 non-dialysis CKD patients and 136 age- and sex-matched controls that required hospitalization due to COVID-19. Patients with end-stage renal disease, a kidney transplant or without registered baseline glomerular filtration rate prior to COVID-19 infection were excluded. CKD and acute kidney injury (AKI) were defined according to KDIGO criteria. Results: CKD patients had higher white blood cell count and D-dimer and lower lymphocyte percentage. No differences were found regarding symptoms on admission. CKD was associated with higher rate of AKI (61 vs. 24.3%) and mortality (40.4 vs. 24.3%). Patients with AKI had the highest hazard for death (AKI/non-CKD HR:7.04, 95% CI:2.87-17.29; AKI/CKD HR:5.25, 95% CI: 2.29-12.02), followed by CKD subjects without AKI (HR:3.39, 95% CI:1.36-8.46). CKD status did not condition ICU admission or length of in-hospital stay. Conclusions: CKD patients that require hospitalization due to COVID-19 are exposed to higher risk of death and AKI.

Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19.

BACKGROUND: COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. METHODS: A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. RESULTS: The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183-12.968], 0.025), viral RNA load (N1) (1.962 [1.244-3.096], 0.004); viral RNA load (N2) (2.229 [1.382-3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). CONCLUSIONS: SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.

Validation of a survival benefit estimator tool in a cohort of European kidney transplant recipients.

Pre-transplant prognostic scores help to optimize donor/recipient allocation and to minimize organ discard rates. Since most of these scores come from the US, direct application in non-US populations is not advisable. The Survival Benefit Estimator (SBE), built upon the Estimated Post-Transplant Survival (EPTS) and the Kidney Donor Profile Index (KDPI), has not been externally validated. We aimed to examine SBE in a cohort of Spanish kidney transplant recipients. We designed a retrospective cohort-based study of deceased-donor kidney transplants carried out in two different Spanish hospitals. Unadjusted and adjusted Cox models were applied for patient survival. Predictive models were compared using Harrell's C statistics. SBE, EPTS and KDPI were independently associated with patient survival (p ≤ 0.01 in all models). Model discrimination measured with Harrell's C statistics ranged from 0.57 (KDPI) to 0.69 (SBE) and 0.71 (EPTS). After adjustment, SBE presented similar calibration and discrimination power to that of EPTS. SBE tended to underestimate actual survival, mainly among high EPTS recipients/high KDPI donors. SBE performed acceptably well at discriminating post-transplant survival in a cohort of Spanish deceased-donor kidney transplant recipients, although its use as the main allocation guide, especially for high KDPI donors or high EPTS recipients requires further testing.

Role of the Furosemide Stress Test in Renal Injury Prognosis.

Risk stratification and accurate patient prognosis are pending issues in the management of patients with kidney disease. The furosemide stress test (FST) has been proposed as a low-cost, fast, safe, and easy-to-perform test to assess tubular integrity, especially when compared to novel plasma and urinary biomarkers. However, the findings regarding its clinical use published so far provide insufficient evidence to recommend the generalized application of the test in daily clinical routine. Dosage, timing, and clinical outcomes of the FST proposed thus far have been significantly different, which further accentuates the need for standardization in the application of the test in order to facilitate the comparison of results between series. This review will summarize published research regarding the usefulness of the FST in different settings, providing the reader some insights about the possible implications of FST in clinical decision-making in patients with kidney disease and the challenges that research will have to address in the near future before widely applying the FST.

Near-Infrared Spectroscopy Monitoring in Cardiac and Noncardiac Surgery: Pairwise and Network Meta-Analyses.

Goal-directed therapy based on brain-oxygen saturation (bSo2) is controversial and hotly debated. While meta-analyses of aggregated data have shown no clinical benefit for brain near-infrared spectroscopy (NIRS)-based interventions after cardiac surgery, no network meta-analyses involving both major cardiac and noncardiac procedures have yet been undertaken. Randomized controlled trials involving NIRS monitoring in both major cardiac and noncardiac surgery were included. Aggregate-level data summary estimates of critical outcomes (postoperative cognitive decline (POCD)/postoperative delirium (POD), acute kidney injury, cardiovascular events, bleeding/need for transfusion, and postoperative mortality) were obtained. NIRS was only associated with protection against POCD/POD in cardiac surgery patients (pooled odds ratio (OR)/95% confidence interval (CI)/I2/number of studies (n): 0.34/0.14-0.85/75%/7), although a favorable effect was observed in the analysis, including both cardiac and noncardiac procedures. However, the benefit of the use of NIRS monitoring was undetectable in Bayesian network meta-analysis, although maintaining bSo2 > 80% of the baseline appeared to have the most pronounced impact. Evidence was imprecise regarding acute kidney injury, cardiovascular events, bleeding/need for transfusion, and postoperative mortality. There is evidence that brain NIRS-based algorithms are effective in preventing POCD/POD in cardiac surgery, but not in major noncardiac surgery. However, the specific target bSo2 threshold has yet to be determined.

Nosocomial Vs. Community-Acquired Infective Endocarditis in Spain: Location, Trends, Clinical Presentation, Etiology, and Survival in the 21st Century.

Major changes have occurred in the epidemiology and etiology of infective endocarditis (IE). Nevertheless, the differences between nosocomial infective endocarditis (NIE) and community-acquired infective endocarditis (CIE) have not been addressed in a population-based study. We conducted a retrospective, nationwide, temporal trend study from 1997 to 2014 analyzing the epidemiology, clinical, geographical, meteorological characteristics of patients diagnosed with IE in Spain, to distinguish NIE from CIE. Among 25,952 patients with IE (62.2 ± 18·6 years; 65.9% men), 45.9% had NIE. The incidence of IE increased from 2.83 to 3.73 due to the NIE incidence increment with a decline in CIE. Patients with NIE were older (63.8 years vs. 60.8 years, p < 0·001), presented a higher Charlson index (1.22 vs. 1.03, p < 0.001), a greater history of implanted cardiac devices (8.7% vs. 4.6%, p < 0.001), and higher mortality (31.5% vs. 21.7%, p < 0.001). The most frequent microorganism for both NIE and CIE was Staphylococcus (p < 0.001), and the North reported a higher incidence (p < 0.001). Risk factors of mortality for NIE were age, Charlson index, hemodialysis, shock, heart failure, and stroke. Risk factors for CIE included female sex, renal disease, and cardiac-device carriers. The etiology of IE shifted from community origins to mostly nosocomial-associated infections. Higher morbidity, mortality, and poorer outcomes are associated with NIE.