Can the Glasgow prognostic score predict ischemic stroke in patients with infective endocarditis?

OBJECTIVE: The Glasgow prognosis score is a simple parameter calculated using serum levels of albumin and C-reactive protein. The aim of this study was to examine whether this parameter may predict ischemic stroke in patients with infective endocarditis. METHODS: A total of 80 patients who were diagnosed with definitive infective endocarditis according to Duke criteria between 2016 and 2023 were included in the study. Glasgow prognosis score was based on serum levels of albumin and C-reactive protein. In imaging methods, patients were divided into two groups according to whether they had a stroke or not. These two groups were compared in terms of biochemical parameters, and infective endocarditis findings on echocardiography and Glasgow prognosis score. RESULTS: We found that the results were statistically similar except for serum C-reactive protein (Group 1: 54.9±71.1 and Group 2: 39±70.7; p=0.03), neutrophil (Group 1: 19.8±10.8*109/L and Group 2: 13.3±7.3*109/L; p=0.014), albumin (Group 1: 2.3±0.6 and Group 2: 2.8±0.5; p=0.03), and Glasgow prognosis score (Group 1: median 2, min.-max. (1-2) and Group 2: median 1, min.-max. (0-1); p=0.004). In the receiver operating characteristics analysis, Glasgow prognosis score had 82.4% sensitivity and 58.3% specificity in predicting ischemic stroke if the Glasgow prognosis score cutoff was ≥1. In multivariate logistic regression analysis, chronic renal failure [odds ratio (OR): 1.098; 95% confidence interval: 1.054-1.964; p=0.044], age (OR: 1.050; 95%CI 1.006-1.096; p=0.024), and Glasgow prognosis score (OR: 0.695; 95%CI 0.411-0.949; p=0.035) were independent variables in predicting ischemic stroke. CONCLUSION: High Glasgow prognosis score is an independent predictor of ischemic stroke in patients with infective endocarditis. Glasgow prognosis score, determined using albumin and C-reactive protein levels, is a simple and practical index for predicting the prognosis of patients hospitalized with infective endocarditis.

U-Shaped Association Between Serum Uric Acid and Short-Term Mortality in Patients With Infective Endocarditis.

Background: Increased uric acid (UA) levels have been reported to be associated with poor clinical outcomes in several conditions. However, the prognostic value of UA in patients with infective endocarditis (IE) is yet unknown. Methods: A total of 1,117 patients with IE were included and divided into two groups according to the current definition of hyperuricemia (UA>420 µmol/L in men and >360 µmol/L in women): hyperuricemia group (n=336) and normouricemia group (n=781). The association between the UA level and short-term outcomes were examined. Results: The in-hospital mortality was 6.2% (69/1117). Patients with hyperuricemia carried a higher risk of in-hospital death (9.8% vs. 4.6%, p=0.001). Hyperuricemia was not an independent risk factor for in-hospital death (adjusted odds ratio [aOR]=1.92, 95% confidence interval [CI]: 0.92-4.02, p=0.084). A U-shaped relationship was found between the UA level and in-hospital death (p<0.001). The in-hospital mortality was lower in patients with UA in the range 250-400 µmol/L. The aOR of in-hospital death in patients with UA>400 and <250 µmol/L was 3.48 (95% CI: 1.38-8.80, p=0.008) and 3.28 (95%CI: 1.27-8.51, p=0.015), respectively. Furthermore, UA>400 µmol/L (adjusted hazard ratio [aHR]=3.54, 95%CI: 1.77-7.07, p<0.001) and <250 µmol/L (aHR=2.23, 95%CI: 1.03-4.80, p=0.041) were independent risk factors for the 6-month mortality. Conclusion: The previous definition of hyperuricemia was not suitable for risk assessment in patients with IE because of the U-shaped relationship between UA levels and in-hospital death. Low and high levels of UA were predictive of increased short-term mortality in IE patients.

Infective Endocarditis-Associated Purpura and Glomerulonephritis Mimicking IgA Vasculitis: A Diagnostic Pitfall.

BACKGROUND: Purpura and glomerulonephritis are typical presentations in IgA vasculitis. Infective endocarditis mimicking IgA vasculitis by presenting with glomerulonephritis and purpura is rarely reported. METHODS: We searched for cases with infective endocarditis-associated purpura and glomerulonephritis in a tertiary hospital in China and retrospectively reviewed their clinicopathological features. Differential diagnosis and treatment in patients with infective endocarditis-associated purpura and glomerulonephritis were discussed. RESULTS: A total of 20 cases with infective endocarditis-associated purpura and glomerulonephritis were identified among 548 cases with infective endocarditis in our center during an 8-year period: 7 of the 20 cases (35%) were initially misdiagnosed as IgA vasculitis and 10 cases (50%) presented with left-sided endocarditis caused by Streptococcus viridans. Fever (100%, 20 out of 20), prior valvular deformities (80%, 16 out of 20), cardiac murmur (95%, 19 out of 20), splenomegaly (84%, 16 out of 19), embolism (55%, 11 out of 20), and hypocomplementemia (76%, 13 out of 17) were present in most patients. Crescents and mesangial hypercellularity with or without endothelial hypercellularity were the primary findings on light microscopy, with C3-dominant deposition on immunofluorescence. But IgA-dominant staining was also observed (40%, 2 out of 5). In patients with rapidly progressive glomerulonephritis, patients with complete recovery of renal function had shorter disease duration and higher ratio (67% vs 20%) of immunosuppressive therapy compared with patients with partial recovery. CONCLUSIONS: Infective endocarditis-associated glomerulonephritis and purpura can closely mimic IgA vasculitis. Differential diagnosis is challenging, particularly when typical presentations of infective endocarditis are absent. In adults with presentations like IgA vasculitis, infective endocarditis should be evaluated through comprehensive clinical and pathological investigations. Immunosuppressive therapy can be considered in patients with severe glomerulonephritis who do not improve after proper anti-infective therapy.

The effect of perioperative hemadsorption in patients operated for acute infective endocarditis-A randomized controlled study.

Patients operated for infective endocarditis (IE) are at high risk of developing an excessive systemic hyperinflammatory state, resulting in systemic inflammatory response syndrome and septic shock. Hemoadsorption (HA) by cytokine adsorbers has been successfully applied to remove inflammatory mediators. This randomized controlled trial investigates the effect of perioperative HA therapy on inflammatory parameters and hemodynamic status in patients operated for IE. A total of 20 patients were randomly assigned to either HA therapy or the control group. HA therapy was initiated intraoperatively and continued for 24 hours postoperatively. Cytokine levels (IL-6, IL-1b, TNF-α), leukocytes, C-reactive protein (CRP), and Procalcitonin (PCT) as well as catecholamine support, and volume requirement were compared between both groups. Operative procedures included aortic (n = 7), mitral (n = 6), and multiple valve surgery (n = 7). All patients survived to discharge. No significant differences concerning median cytokine levels (IL-6 and TNF-α) were observed between both groups. CRP and PCT baseline levels were significantly higher in the HA group (59.5 vs. 26.3 mg/dL, P = .029 and 0.17 vs. 0.05 µg/L, P = .015) equalizing after surgery. Patients in the HA group required significantly higher doses of vasopressors (0.093 vs. 0.025 µg/kg/min norepinephrine, P = .029) at 12 hours postoperatively as well as significantly more overall volume replacement (7217 vs. 4185 mL at 12 hours, P = .015; 12 021 vs. 4850 mL at 48 hours, P = .015). HA therapy did neither result in a reduction of inflammatory parameters nor result in an improvement of hemodynamic parameters in patients operated for IE. For a more targeted use of HA therapy, appropriate selection criteria are required.

Prognostic value of D-dimer for adverse outcomes in patients with infective endocarditis: an observational study.

BACKGROUND: Increased D-dimer levels have been shown to correlate with adverse outcomes in various clinical conditions. However, few studies with a large sample size have been performed thus far to evaluate the prognostic value of D-dimer in patients with infective endocarditis (IE). METHODS: 613 patients with IE were included in the study and categorized into two groups according to the cut-off of D-dimer determined by receiver operating characteristic (ROC) curve analysis for in-hospital death: > 3.5 mg/L (n = 89) and ≤ 3.5 mg/L (n = 524). Multivariable regression analysis was used to determine the association of D-dimer with in-hospital adverse events and six-month death. RESULTS: In-hospital death (22.5% vs. 7.3%), embolism (33.7% vs 18.2%), and stroke (29.2% vs 15.8%) were significantly higher in patients with D-dimer > 3.5 mg/L than in those with D-dimer ≤ 3.5 mg/L. Multivariable analysis showed that D-dimer was an independent risk factor for in-hospital adverse events (odds ratio = 1.11, 95% CI 1.03-1.19, P = 0.005). In addition, the Kaplan-Meier curve showed that the cumulative 6-month mortality was significantly higher in patients with D-dimer > 3.5 mg/L than in those with D-dimer ≤ 3.5 mg/L (log-rank test = 39.19, P < 0.0001). Multivariable Cox regression analysis showed that D-dimer remained a significant predictor for six-month death (HR 1.11, 95% CI 1.05-1.18, P < 0.001). CONCLUSIONS: D-dimer is a reliable prognostic biomarker that independently associated with in-hospital adverse events and six-month mortality in patients with IE.

Prognostic value of pro-adrenomedullin and copeptin in acute infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is a life-threatening disease whose prognosis is often difficult to predict based on clinical data. Biomarkers have been shown to favorably affect disease management in a number of cardiac disorders. Aims of this retrospective study were to assess the prognostic role of procalcitonin (PCT), pro-adrenomedullin (pro-ADM) and copeptin in IE and their relation with disease characteristics and the traditional biomarker C-reactive protein (CRP). METHODS: We studied 196 patients with definite IE. Clinical, laboratory and echocardiography parameters were analyzed, with a focus on co-morbidities. PCT, pro-ADM and copeptin were measured on stored plasma samples obtained on admission during the acute phase of the disease. RESULTS: Pro-ADM and copeptin were significantly higher in older patients and associated with prior chronic kidney disease. Pro-ADM was an independent predictor of hospital mortality (OR 3.29 [95%C.I. 1.04-11.5]; p = 0.042) whilst copeptin independently predicted 1-year mortality (OR 2.55 [95%C.I. 1.18-5.54]; p = 0.017). A high PCT value was strictly tied with S. aureus etiology (p = 0.001). CRP was the only biomarker associated with embolic events (p = 0.003). CONCLUSIONS: Different biomarkers correlate with distinct IE outcomes. Pro-ADM and copeptin may signal a worse prognosis of IE on admission to the hospital and could be used to identify patients who need more aggressive treatment. CRP remains a low-cost marker of embolic risk. A high PCT value should suggest S. aureus etiology.

Staphylococcal Enterotoxins and Toxic Shock Syndrome Toxin-1 and Their Association among Bacteremic and Infective Endocarditis Patients in Egypt.

PURPOSE: Infective endocarditis (IE) is a major complication in patients with bacteremia of Staphylococcus (S.) aureus infection. Our aim was to determine the association of the major Staphylococcal superantigens (SAgs), including Staphylococcal enterotoxins (SEs) and toxic shock syndrome toxin-1 (TSST-1), among hospitalized patients diagnosed with bacteremia and those with IE. METHODS: This study was conducted on 88 patients; of these, 84 (95.5%) had two positive blood cultures. Eighteen out of the 84 patients (21.4%) were diagnosed based on the modified Duke criteria by a cardiologist to have IE. The recovered isolates were screened phenotypically using ELISA followed by molecular analysis of sea, seb, sec, sed, see, and tsst-1, the major SAg coding genes, and the obtained findings were statistically analyzed. RESULTS: Phenotypic screening for SE production of 26 selected Staphylococci (15 isolated from the IE patients (10 S. aureus and 5 coagulase negative staphylococci (CoNS)) and 11 from bacteremic patients (10 S. aureus and 1 CoNS)) using ELISA revealed that 12/26 (46%) isolates were SE producers. PCR analysis showed that 19 (73%) isolates were PCR positive for SAg genes with the highest prevalence of the sea gene (79%), followed by seb (63%) and tsst-1 (21%). The least frequent gene was sed (5.3%). Statistical correlations between bacteremic and IE isolates with respect to prevalence of SAgs showed no significant difference (P value = 0.139, effect size = 0.572) indicating no specific association between any of the detected SAgs and IE. CONCLUSION: There is high prevalence of SEs among clinical isolates of Staphylococci recovered from patients suffering bacteremia and those with IE. No significant difference was found among Staphylococcal isolates recovered from patients with bacteremia or IE regarding both phenotypic and genotypic detection of the tested SAgs.

Exploring Potential Proteomic Biomarkers for Prognosis of Infective Endocarditis through Profiled Autoantibodies by an Immunomics Protein Array Technique.

Though infective endocarditis (IE) is a life-threatening cardiac infection with a high mortality rate, the effective diagnostic and prognostic biomarkers for IE are still lacking. The aim of this study was to explore the potential applicable proteomic biomarkers for IE through the Immunome™ Protein Array system. The system was employed to profile those autoantibodies in IE patients and control subjects. Our results showed that interleukin-1 alpha (IL1A), nucleolar protein 4 (NOL4), tudor and KH domain-containing protein (TDRKH), G antigen 2B/2C (GAGE2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and X antigen family member 2 (XAGE2) are highly differentially-expressed among IE and non-IE control. Furthermore, bactericidal permeability-increasing protein (BPI), drebrin-like protein (DBNL), signal transducing adapter molecule 2 (STAM2), cyclin-dependent kinase 16 (CDK16), BAG family molecular chaperone regulator 4 (BAG4), and nuclear receptor-interacting protein 3 (NRIP3) are differentially-expressed among IE and healthy controls. On the other hand, those previously identified biomarkers for IE, including erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, procalcitonin, and N-terminal-pro-B-type natriuretic peptide demonstrated only minor significance. With scientific rationalities for those highly differentially-expressed proteins, they could serve as potential candidates for diagnostic biomarkers of IE for further analysis.

Injection Drug Use-Associated Candidemia: Incidence, Clinical Features, and Outcomes, East Tennessee, 2014-2018.

BACKGROUND: Injection drug use (IDU) is an established but uncommon risk factor for candidemia. Surveillance for candidemia is conducted in East Tennessee, an area heavily impacted by the opioid crisis and IDU. We evaluated IDU-associated candidemia to characterize the epidemiology and estimate the burden. METHODS: We assessed the proportion of candidemia cases related to IDU during January 1, 2014-September 30, 2018, estimated candidemia incidence in the overall population and among persons who inject drugs (PWID), and reviewed medical records to compare clinical features and outcomes among IDU-associated and non-IDU candidemia cases. RESULTS: The proportion of IDU-associated candidemia cases in East Tennessee increased from 6.1% in 2014 to 14.5% in 2018. Overall candidemia incidence in East Tennessee was 13.5/100 000, and incidence among PWID was 402-1895/100 000. Injection drug use-associated cases were younger (median age, 34.5 vs 60 years) and more frequently had endocarditis (39% vs 3%). All-cause 30-day mortality was 8% among IDU-associated cases versus 25% among non-IDU cases. CONCLUSIONS: A growing proportion of candidemia in East Tennessee is associated with IDU, posing an additional burden from the opioid crisis. The lower mortality among IDU-associated cases likely reflects in part the younger demographic; however, Candida endocarditis seen among approximately 40% underscores the seriousness of the infection and need for prevention.

Factors associated with delayed diagnosis of infective endocarditis: A retrospective cohort study in a teaching hospital in Japan.

Patients with infective endocarditis (IE), have high mortality and morbidity, however, its early diagnosis is difficult. Few studies have examined the delayed diagnosis of IE. We aimed to investigate the factors associated with the diagnostic delay of IE.A retrospective cohort study was conducted for consecutive patients diagnosed with IE in an acute care teaching hospital in Japan from April 2006 to March 2018. Time-to-diagnosis was analyzed using a multivariate Cox hazard model for determining factors associated with days required for IE diagnosis. Factors analyzed in the model included age, gender, activities of daily living, Charlson comorbidity index, presence of internal device, chief complaint, inappropriate antibiotics use, shaking chill, fever >38°C, hypoxemia, serum C-reactive protein (CRP) < 10 mg/dL, Staphylococcus aureus as causative pathogen, findings on first echocardiography, resident as a first contact physician, primary care physician as a first contact doctor, and transport measures to the clinic/hospital.There were 145 IE patients with a mean age of 70 years and 90 were male (62.1%). The median time to the diagnosis of definite IE was 13 days and median time to consider the diagnosis of IE from first clinic/hospital visit was 6 days. The time to consider IE diagnosis was significantly delayed in patients who had inappropriate prior antibiotic use (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.01 to 2.57; P = .045), in patients without fever >38°C (HR, 1.80; 95% CI, 1.11 to 2.90; P = .016), in patients with serum CRP level < 10 mg/dL (HR, 1.53; 95% CI, 1.01 to 2.33; P = .046), and in patients who did not use an ambulance for hospital arrival (HR, 3.18; 95% CI, 1.72 to 5.85; P < .001).Delay in considering IE diagnosis is associated with inappropriate prior antibiotics use, absence of high fever, absence of high CRP level, and use of a hospital arrival vehicle other than an ambulance. For earlier IE diagnosis, inappropriate use of antibiotics should be avoided and IE should not be excluded by relatively low level of temperature or serum CRP.

Antineutrophil cytoplasmic antibodies (ANCA)-positive patient with infective endocarditis and chronic hepatitis B virus: a case report and review of the literature.

BACKGROUND: Antineutrophil cytoplasmic antibodies comprise a family of autoantibodies that are often used as biomarkers for certain forms of small-vessel vasculitis; however, chronic infections tend to induce the production of antineutrophil cytoplasmic antibodies. Infective endocarditis and hepatitis B virus infection have been reported to exhibit antineutrophil cytoplasmic antibody positivity and to mimic antineutrophil cytoplasmic antibody-associated vasculitis, which may lead to misdiagnosis and inappropriate treatment. CASE PRESENTATION: We report a case of a 46-year-old Han Chinese man with untreated chronic hepatitis B virus infection who featured proteinase-3 antineutrophil cytoplasmic antibody positivity while hospitalized with infective endocarditis. Cardiac ultrasound echocardiography disclosed mitral and aortic regurgitation with vegetation. On the 15th hospital day, the patient underwent mitral and aortic valve replacement and was then treated with antibiotics for more than 1 month. On the 57th hospital day, the patient was discharged. His urinary abnormalities and renal function were gradually recovering. Four months after being discharged, his proteinase-3 antineutrophil cytoplasmic antibody levels had returned to the normal range. CONCLUSIONS: The findings in this study update and expand current understanding of antineutrophil cytoplasmic antibody positivity in patients with both infective endocarditis and hepatitis B virus. Treatment (including surgery, antibiotics, corticosteroids and/or cyclophosphamide, antiviral agents, and even plasma exchange) is challenging when several diseases are combined. Renal biopsy is suggested if the patient's condition allows. Antineutrophil cytoplasmic antibody testing should be repeated after therapy, because some cases might require more aggressive treatment.

Red Blood Cell Distribution Width Predicts Postoperative Death of Infective Endocarditis.

Infectious endocarditis (IE) is a rare disease with high mortality rate. Recently, red cell distribution width (RDW) has drawn special attention for predicting cardiovascular disease. This study aims to explore the relationship between RDW value and postoperative death of IE patients.Clinical records of patients with definite IE from Chinese People's Liberation Army General Hospital department of cardiovascular surgery were collected and analyzed. Clinical, echocardiographic, and biochemical variables were evaluated along with RDW.Results: A total of 158 consecutive IE patients (mean age 47.0 ± 16.3 years, male 61.4%) were enrolled in this study. According to receiver operating characteristic (ROC) curve analysis, the optimal RDW cutoff value for predicting mortality was 15.45% (area under the curve 0.913, P < 0.001). A total of 28 patients (17.8%) died postoperatively; of these, 89.3% had RDW value >15.45%. Binary regression analysis showed that aging, multiple valvular involved, valvular vegetation formation, pulmonary hypertension, and high RDW are strong predictors of postoperative death. Multiple regression analysis revealed that high RDW value was independent predictors of postoperative mortality in patients with IE (ß: 3.704, 95% confidence interval (95%CI): 2.729-604.692, P < 0.05).IE has a high inhospital mortality rate, and increased RDW is an independent predictor of postoperative death in these patients.

Biomarkers for prediction of mortality in left-sided infective endocarditis.

BACKGROUND: Evidence regarding biomarkers for risk prediction in patients with infective endocarditis (IE) is limited. We aimed to investigate the value of a panel of biomarkers for the prediction of in-hospital mortality in patients with IE. METHODS: Between 2016 and 2018, consecutive IE patients admitted to the emergency department were prospectively included. Blood concentrations of nine biomarkers were measured at admission (D0) and on the seventh day (D7) of antibiotic therapy: C-reactive protein (CRP), sensitive troponin I (s-cTnI), procalcitonin, B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL6), tumor necrosis factor α (TNF-α), proadrenomedullin, alpha-1-acid glycoprotein, and galectin 3. The primary endpoint was in-hospital mortality. RESULTS: Among 97 patients, 56% underwent cardiac surgery, and in-hospital mortality was 27%. At admission, six biomarkers were independent predictors of in-hospital mortality: s-cTnI (OR 3.4; 95%CI 1.8-6.4; P<0.001), BNP (OR 2.7; 95%CI 1.4-5.1; P=0.002), IL-6 (OR 2.06; 95%CI 1.3-3.7; P=0.019), procalcitonin (OR 1.9; 95%CI 1.1-3.2; P=0.018), TNF-α (OR 1.8; 95%CI 1.1-2.9; P=0.019), and CRP (OR 1.8; 95%CI 1.0-3.3; P=0.037). At admission, S-cTnI provided the highest accuracy for predicting mortality (area under the ROC curve: s-cTnI 0.812, BNP 0.727, IL-6 0.734, procalcitonin 0.684, TNF-α 0.675, CRP 0.670). After 7 days of antibiotic therapy, BNP and inflammatory biomarkers improved their performance (s-cTnI 0.814, BNP 0.823, IL-6 0.695, procalcitonin 0.802, TNF-α 0.554, CRP 0.759). CONCLUSION: S-cTnI concentration measured at admission had the highest accuracy for mortality prediction in patients with IE.

Towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysis.

INTRODUCTION: Infective endocarditis (IE) has high mortality, partly due to delayed diagnosis. No biomarker can identify IE in patients with fever and clinical picture of infection. To find putative biomarkers we analyzed serum levels of two proteins found in cardiac valves, fibulin-1 (n=696) and osteoprotegerin (n=689) among patients on clinical suspicion of IE. Proteomic analyses were performed in 24 patients with bacteremia, 12 patients with definite IE and 12 patients with excluded IE. METHODS: Fibulin-1 and osteoprotegerin were studied by enzyme linked immunosorbent assay (ELISA). Proteomic analyses were conducted by 2-dimensional polyacrylamid gel electrophoresis (2D-PAGE) and label-free quantitative liquid chromatography - tandem mass spectrometry (LFQ LC-MS/MS). Controls for 2D 2D-PAGE and LFQ LC-MS/MS had bacteremia and excluded IE. RESULTS: Osteoprotegerin levels were significantly increased in IE patients compared with non-IE patients. Fibulin-1 showed no difference. 2D-PAGE showed significant differences of 6 proteoforms: haptoglobin, haptoglobin-related protein, α-2-macroglobulin, apolipoprotein A-I and ficolin-3. LFQ LC-MS/MS analysis revealed significant level changes of 7 proteins: apolipoprotein L1, complement C1q subcomponent B and C, leukocyte immunoglobulin-like receptor subfamily A member 3, neuropilin-2, multimerin-1 and adiponectin. CONCLUSIONS: The concentration changes in a set of proteoforms/proteins suggest that stress and inflammation responses are perturbed in patients with IE compared to patients with bacteremia without IE.

Changes in inflammatory and vasoactive mediator profiles during valvular surgery with or without infective endocarditis: A case control pilot study.

BACKGROUND: More than 50% of patients with infective endocarditis (IE) develop an indication for surgery. Despite its benefit, surgery is associated with a high incidence of multiple organ dysfunction syndrome (MODS) and mortality, which may be linked to increased release of inflammatory mediators during cardiopulmonary bypass (CPB). We therefore assessed plasma cytokine profiles in patients undergoing valve surgery with or without IE. METHODS: We performed a prospective case-control pilot study comparing patients undergoing cardiac valve surgery with or without IE. Plasma profiles of inflammatory mediators were measured at 7 defined time points and reported as median (interquartile). The degree of MODS was measured using sequential organ failure assessment (SOFA) score. RESULTS: Between May and December 2016 we included 40 patients (20 in each group). Both groups showed similar distribution of age and gender. Patients with IE had higher preoperative SOFA (6.9± 2.6 vs 3.8 ± 1.1, p<0.001) and operative risk scores (EuroSCORE II 18.6±17.4 vs. 1.8±1.3, p<0.001). In-hospital mortality was higher in IE patients (35% vs. 5%; p<0.001). Multiple organ failure was the cause of death in all non-survivors. At the end of CPB, median levels of following inflammatory mediators were higher in IE compared to control group: IL-6 (119.73 (226.49) vs. 24.48 (40.09) pg/ml, p = 0.001); IL-18 (104.82 (105.99) vs. 57.30 (49.53) pg/ml, p<0.001); Mid-regional pro-adrenomedullin (MR-proADM) (2.06 (1.58) vs. 1.11 (0.53) nmol/L, p = 0.003); MR- pro-atrial natriuretic peptide (MR-proANP) (479.49 (224.74) vs. 266.55 (308.26) pmol/l, p = 0.028). IL-1ß and TNF- α were only detectable in IE patients and first after starting CPB. Plasma levels of IL-6, IL-18, MRproADM, and MRproANP during CPB were significantly lower in survivors than in those who died. CONCLUSION: The presence of infective endocarditis during cardiac valve surgery is associated with increased inflammatory response as evident by higher plasma cytokine levels and other inflammatory mediators. Actively reducing inflammatory response appears to be a plausible therapeutic concept. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02727413.

Clinical characteristics of infective endocarditis in patients with antineutrophil cytoplasmic antibody or antiphospholipid antibody: a retrospective study in Shanghai.

OBJECTIVE: This study aimed to characterise rheumatic manifestations and autoantibodies in 432 patients diagnosed with infective endocarditis (IE) in Shanghai. DESIGN, SETTING AND PARTICIPANTS: A retrospective study was conducted in Ruijin Hospital from 1997 to 2017. The clinical and laboratory characteristics of a total of 432 patients were analysed. In addition, the differences between patients with positive and negative antineutrophil cytoplasmic antibodies (ANCA) and antiphospholipid (aPL) antibodies as well as the survival rates of these patients were compared. RESULTS: A total of 432 patients, including 278 male patients and 154 female patients, were included. The mean age of the patients was 46±16 years. A total of 346 patients (80%) had cardiac surgery, and 55 patients (13%) died in the hospital. Among the IE patients, 104 were tested for either ANCA or aPL and were analysed in different groups. Twenty-one (24%) positive ANCA patients were proteinase 3-ANCA positive. Compared with the ANCA-negative group, patients with positive ANCA had higher IgM (p=0.048), lower haemoglobin (p=0.001) and a higher likelihood of arthritis (p=0.003). Twenty-one (40%) aPL-positive patients had a higher erythrocyte sedimentation rate than was found in the aPL-negative group (p=0.003). In addition, the survival rate of the ANCA-positive IE patients was lower (p=0.032) than that of the ANCA-negative group, while there was no difference between patients with or without aPL antibodies (p=0.728). CONCLUSION: This study supports the claim that rheumatic manifestations and autoantibodies are frequently present in patients with IE and might lead to early misdiagnosis. Physicians should pay more attention to the measurement of autoantibodies in these patients.

High level of D-dimer predicts ischemic stroke in patients with infective endocarditis.

BACKGROUND: Ischemic stroke is one of the most prominent and serious neurological complications of infective endocarditis (IE). Our study was designed to evaluate the predictive value of higher level of plasma D-dimer on admission for the development of ischemic stroke in patients with IE. METHODS: In this prospective study, a total of 173 consecutive patients with IE were recruited from January 2016 to December 2018. Plasma D-dimer and other clinical indexes of IE patients were measured after admission. The number of patients who developed ischemic stroke during 6-month follow-up was recorded, as well as the occurrence time of ischemic stroke. RESULTS: Ischemic stroke was observed in 38 (22%) patients during 6-month follow-up since definite diagnosis of IE. Patients with ischemic stroke had significantly higher levels of plasma D-dimer than those of patients without stroke (4982 vs 2205 µg/L, P < .001). In addition, Staphylococcus aureus infection (HR: 1.96, 95% CI: 1.51-2.42), mitral valve vegetation (HR: 1.52, 95% CI: 1.32-1.75), and higher levels of on-admission plasma D-dimer (HR: 1.35, 95% CI: 1.27-1.43) were significantly associated with ischemic stroke. Moreover, D-dimer levels ≥3393 µg/L served as a strong predictor for ischemic stroke in patients with IE, and the sensitivity and specificity were 78% and 83%, respectively. CONCLUSION: Our study suggested that higher level of D-dimer on admission was an independent predictor for ischemic stroke in patients with IE. These patients may require special attention, in particular within the first trimester after IE diagnosis.

Effect of conjugated bilirubin on clinical outcomes in infective endocarditis.

Liver dysfunction is associated with adverse events in infective endocarditis (IE). However, few studies have explored the predictive value of conjugated bilirubin (CB) in IE. We aimed to investigate the nature of the link between CB and adverse prognosis in patients with IE. Consecutive patients with IE between January 2009 and July 2015 were enrolled. Multivariate analysis was performed to confirm whether CB was an independent risk factor for adverse outcomes. In all, 1010 patients were included and divided into two groups according to admission CB level (µmol/L): normal (≤ 7.0, n = 820) and elevated (> 7.0, n = 190) CB groups. In-hospital mortality (5.0% vs. 22.1%, p < 0.001) and major adverse cardiac events (16.8% vs. 36.3%, p < 0.001) were significantly higher in patients with increased CB. A possible J-shaped relationship was found between CB and in-hospital events. Further, CB had more predictive power than total bilirubin in predicting in-hospital death (AUC 0.715 vs. 0.674, p = 0.010). Elevated CB was an independent predictor of in-hospital death (adjusted OR = 2.62, 95%CI 1.40-4.91, p = 0.003). Moreover, CB (increment 1 µmol/L) was independently associated with higher long-term mortality. Kaplan-Meier curves indicated that patients with elevated CB were associated with higher cumulative rate of long-term death (log-rank = 21.47, p < 0.001). CB, a biomarker of liver function, was a relatively powerful predictor of in-hospital and long-term adverse prognosis of IE and could likely comprise a novel risk evaluation strategy.

Inflammatory markers in the diagnostic workup of pacemaker- and defibrillator­related infections in patients referred for transvenous lead extraction.

BACKGROUND: Infectious complications can be life­threatening in patients with permanent transvenous pacemakers and their diagnosis can be challenging. AIMS: The aim of the study was to assess the diagnostic utility of white blood cell (WBC) count and C­reactive protein (CRP) concentrations in infectious complications in patients with cardiac pacemakers. METHODS: The prospective study included patients who underwent transvenous lead extraction (TLE) due to various indications. The diagnosis of lead­dependent infective endocarditis (LDIE) was based on the modified Duke criteria, and the diagnosis of local infection was based on symptoms related to device pocket. The study population consisted of 640 patients: 63 (9.9%) with LDIE, 61 (9.5%) with local infection, and 516 controls (80.6%) referred for TLE due to noninfectious indications. We evaluated WBC count and CRP concentrations in each group of patients and assessed the predictive value of these tests for the diagnosis of LDIE and local infection. RESULTS: Patients with local infection did not differ in terms of median WBC and CRP values compared with controls (P = 0.99 and P = 0.13, respectively), whereas patients with LDIE had higher median WBC count and CRP level (P <0.001 and P <0.001, respectively). In the LDIE group, WBC diagnostic test showed 46.0% sensitivity, 95.3% specificity, 90.5% accuracy, 51.8% positive predictive value, and 94.2% negative predictive value. The diagnostic test based on CRP levels showed 84.1% sensitivity, 81.8% specificity, 82.0% accuracy, 33.5% positive predictive value, and 97.9% negative predictive value. CONCLUSIONS: In patients undergoing TLE due to infectious indications, inflammatory markers (WBC count, CRP level) were within normal range in the local­infection group and markedly elevated in the LDIE group. Inflammatory markers were useful to determine the extent of the infection in patients with local infection.

Tick-borne pathogens Bartonella spp., Borrelia burgdorferi sensu lato, Coxiella burnetii and Rickettsia spp. may trigger endocarditis.

BACKGROUND: Infections caused by tick-borne pathogens such as Bartonella spp., Borrelia burgdorferi s.l., Coxiella burnetii, and Rickettsia spp. are capable of causing serious lesions of the mitral and aortic valves, leading to a need for valve replacement. OBJECTIVES: The aim of the study was to determine whether such cases are sporadic or frequent. An additional goal was to establish effective diagnostic methods to detect these infections. MATERIAL AND METHODS: The study involved 148 patients undergoing valve replacement. Blood samples were drawn for serological testing. Samples of the removed mitral and aortic valves were tested with polymerase chain reaction and immunohistochemical staining. RESULTS: Specific antibodies to Bartonella spp. were detected in 47 patients (31.7%) and in 1 of the healthy controls (1%) (p < 0.05). Antibodies to B. burgdorferi spirochetes were found in 18 of the patients (12.2%) and in 6 blood donors from the control group (5.8%) (p < 0.1). Antibodies to Rickettsia spp. were detected in 12 (8.1%) and to C. burnetii phase I and II antigens in the serum of 1 patient. All the participants in the control group were seronegative to C. burnetii and Rickettsia spp. antigens. Polymerase chain reaction (PCR) tests for detection of Bartonella spp., B. burgdorferi s.l., C. burnetii and Rickettsia spp. DNA in the valve samples were all negative. Inflammation foci with mononuclear lymphoid cells in the aortic and mitral valves were seen in sections stained with hematoxiline and eozine. In sections dyed using the indirect immunofluorescence method with hyperimmune sera, Bartonella spp. and Rickettsia spp. were found. CONCLUSIONS: The results obtained indicate that laboratory diagnostics for patients with heart disorders should be expanded to include tests detecting tick-borne zoonoses such as bartonelloses, Lyme borreliosis, rickettsioses and Q fever.