Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis.

OBJECTIVES: Host responses to infection are a major determinant of outcome. However, the existence of different response profiles in patients with endocarditis has not been addressed. Our objective was to apply transcriptomics to identify endotypes in patients with infective endocarditis. METHODS: A total of 32 patients with infective endocarditis were studied. Clinical data and blood samples were collected at diagnosis and RNA sequenced. Gene expression was used to identify two clusters (endocarditis endotype 1 [EE1] and endocarditis endotype 2 [EE2]). RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression, and molecular pathways involved were assessed. The identified endotypes were recapitulated in a cohort of COVID-19 patients. RESULTS: A total of 18 and 14 patients were assigned to EE1 and EE2, respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the signal transducer and activator of transcription protein family pathway, with higher counts of active T cells and lower counts of neutrophils. A total of 14 patients (nine in EE1 and five in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression toward a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, P = 0.027), with an adjusted hazard ratio of 12.987 (95% confidence interval 3.356-50). Translation of these endotypes to COVID-19 and non-COVID-19 septic patients yielded similar results in cell populations and outcome. CONCLUSIONS: Gene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, responses to surgery, and outcomes.

Preoperative fibrinogen level predicts the risk and prognosis of patients with native valve infective endocarditis undergoing valve surgery.

Aim: The aim of this study was to assess the clinical significance and prognostic value of the preoperative fibrinogen (FBG) level in patients with native valve infective endocarditis (NVIE) who underwent valve surgery. Methods: This retrospective study included a total of 163 consecutive patients who were diagnosed with NVIE and underwent valve surgery from January 2019 to January 2022 in our hospital. The primary endpoint was all-cause mortality. Results: All-cause mortality was observed in 9.2% of the patients (n = 15). Body mass index (BMI) was lower in the survival group (p = 0.025), whereas FBG (p = 0.008) and platelet count (p = 0.044) were significantly greater in the survival group than in the death group. Multivariate Cox proportional hazards analysis revealed that FBG (HR, 0.55; 95% CI, [0.32-0.94]; p = 0.029) was an independent prognostic factor for all-cause mortality. Furthermore, Kaplan‒Meier survival curve analysis revealed that patients with low FBG levels (<3.28 g/L) had a significantly greater mortality rate (p = 0.034) than did those with high FBG levels (>3.99 g/L). In the trend analysis, the FBG tertiles were significantly related to all-cause mortality in all three adjusted models, and the p values for trend were 0.017, 0.016, and 0.028, respectively. Conclusion: Preoperative FBG may serve as a prognostic factor for all-cause mortality, and an FBG concentration less than 3.28 g/L was associated with a greater risk of all-cause mortality in NVIE patients undergoing valve surgery.

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 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.

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.

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.

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.

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.

Baseline C-reactive protein levels and prognosis in patients with infective endocarditis: A prospective cohort study.

BACKGROUND: Early diagnosis and risk-stratification among infective endocarditis (IE) patients are limited by poor microbiological yield and inadequate characterization of vegetations. A simple tool that can predict adverse outcomes in the early phase of management is required. AIM: To study the prognostic value of C-reactive protein (CRP) levels at admission and its role in predicting various clinical outcomes. METHODS: In a prospective study of consecutive IE patients diagnosed by modified Duke's criteria, we measured the peak levels of CRP and erythrocyte sedimentation rate (ESR) in the first 3 days of admission and correlated it with in-hospital mortality, six-month mortality, embolic phenomena and the need for urgent surgery. Predefined laboratory-microbiological sampling protocols and antibiotic-initiation protocols were followed. Receiver-operating-characteristics curves were generated to identify a reliable cut-off for CRP in predicting various outcomes. RESULTS: Out of 101 patients who were treated, 85 patients had 'definite' IE. Blood cultures were positive in 55% (n = 39); and Staphylococcus species was the most common organism. Major complications occurred in 74.1% (n = 63) and in-hospital mortality was 32.9% (n = 28). Mean ESR and CRP levels were 102 ±â€¯31 mm/h and 51 ±â€¯20 mg/l, respectively. In multivariable analysis, high CRP levels were independently predictive of mortality, major complications, embolic events and need for urgent surgery. A CRP >40 mg/l predicted adverse outcomes with a sensitivity of 73% and specificity of 99%. CONCLUSION: The study shows that baseline CRP level in the first 3 days of admission is a strong predictor of short term adverse outcomes in IE patients, and a useful marker for early risk stratification.

Hemoadsorption treatment of patients with acute infective endocarditis during surgery with cardiopulmonary bypass - a case series.

INTRODUCTION: Infective endocarditis is a serious disease condition. Depending on the causative microorganism and clinical symptoms, cardiac surgery and valve replacement may be needed, posing additional risks to patients who may simultaneously suffer from septic shock. The combination of surgery bacterial spreadout and artificial cardiopulmonary bypass (CPB) surfaces results in a release of key inflammatory mediators leading to an overshooting systemic hyperinflammatory state frequently associated with compromised hemodynamic and organ function. Hemoadsorption might represent a potential approach to control the hyperinflammatory systemic reaction associated with the procedure itself and subsequent clinical conditions by reducing a broad range of immuno-regulatory mediators. METHODS: We describe 39 cardiac surgery patients with proven acute infective endocarditis obtaining valve replacement during CPB surgery in combination with intraoperative CytoSorb hemoadsorption. In comparison, we evaluated a historical group of 28 patients with infective endocarditis undergoing CPB surgery without intraoperative hemoadsorption. RESULTS: CytoSorb treatment was associated with a mitigated postoperative response of key cytokines and clinical metabolic parameters. Moreover, patients showed hemodynamic stability during and after the operation while the need for vasopressors was less pronounced within hours after completion of the procedure, which possibly could be attributed to the additional CytoSorb treatment. Intraoperative hemoperfusion treatment was well tolerated and safe without the occurrence of any CytoSorb device-related adverse event. CONCLUSIONS: Thus, this interventional approach may open up potentially promising therapeutic options for critically-ill patients with acute infective endocarditis during and after cardiac surgery, with cytokine reduction, improved hemodynamic stability and organ function as seen in our patients.

[Antineutrophil cytoplasmic antibodies associated with infective endocarditis: Literature review]. / Endocardites infectieuses associées aux anticorps anticytoplasme des polynucléaires neutrophiles (ANCA) : revue de la littérature.

Antineutrophil cytoplasmic antibodies (ANCA) associated with infective endocarditis are a rare disorder. The condition can mimic primary systemic vasculitis (i.e. granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis). Thus, a wrong diagnosis of valvular involvement related to primary systemic vasculitis can be made in patients exhibiting ANCA associated with infective endocarditis. Because treatment of both conditions is different, this wrong diagnosis will lead to dramatic consequences in these latter patients. This review reports the state of knowledge and proposes an algorithm to follow when confronted to a possible case of ANCA associated with infective endocarditis.

[INFLAMMATION AND CARDIAC INSUFFICIENCY ASSOCIATED WITH INFECTIOUS ENDOCARDITIS].

The study included 62 patients with uncomplicated primary and secondary infectious endocarditis admitted to S.PBotkin city hospital from 2011 to 2014. The emphasis is laid on diagnostic significance of dynamic measurements of the levels of C-reactive protein, tumour necrosis factor and highly sensitive troponin-1 for the evaluation of activity of the infectious/toxic process, severity of the disease, and detection of complications. The study revealed the relationship of the enhanced level of troponin-1 with changes of inflammation markers, morphofunctional characteristics of myocardium, and circulatory failure. Morphologicl study demonstrated inflammatory and dystrophic changes in myocardium, focal and diffuse cardiofibrosis suggesting development of non-coronarogenic myocardial lesions that play an important role in the progress of cardiac failure associated with infectious endocarditis.

Clinical Presentation and Multi-Parametric Screening Surrogates of Ischemic Stroke Patients Suffering from Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) represents a life-threatening condition due to complications like cardiac failure and thromboembolism. In ischemic stroke, IE formally excludes patients from approaches addressing the recanalization of occluded vessels, challenging decision-making in the early phase of hospitalization. This study aimed at the rate and clinical course of stroke patients with IE and explored clinical, imaging-based and serum parameters, which would allow early identification. METHODS: A hospital-based registry containing 1,531 ischemic stroke patients was screened for IE identified by echocardiography. In addition to clinical parameters, patterns of cerebral manifestation as well as a variety of inflammatory serum and myocardial markers were analyzed concerning their predictive impact for identifying affected patients. RESULTS: IE was found in 26 patients (1.7%) and was associated with an increased body temperature and cardiac murmurs. Patients suffering from IE demonstrated a more severe clinical affection at hospital discharge and an impaired symptom decline during hospitalization, further deteriorated by the use of systemic thrombolysis. Distribution of cerebral infarction patterns did not differ between the groups. C-reactive protein (CRP) and leukocyte count as well as troponin and myoglobin, taken at hospital admission, were found to be significantly associated with IE. CONCLUSIONS: IE in stroke patients is associated with worse clinical outcome, complicated by intravenously applied thrombolysis, and therefore needs to be screened during the early phase of hospitalization. Increased serum levels of CRP and leukocyte count in combination with an increased body temperature or abnormal cardiac murmurs should entail rapid initiation of further diagnostics, that is, transoesophageal echocardiography.

Cytokine Signature in Infective Endocarditis.

Infective endocarditis (IE) is a severe disease with high mortality rate. Cytokines participate in its pathogenesis and may contribute to early diagnosis improving the outcome. This study aimed to evaluate the cytokine profile in IE. Serum concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor (TNF)-α were measured by cytometric bead array (CBA) at diagnosis in 81 IE patients, and compared with 34 healthy subjects and 30 patients with non-IE infections, matched to the IE patients by age and gender. Mean age of the IE patients was 47±17 years (range, 15-80 years), and 40 (50%) were male. The IE patients had significantly higher serum concentrations of IL-1ß, IL-6, IL-8, IL-10 and TNF-α as compared to the healthy individuals. The median levels of IL-1ß, TNF-α and IL-12 were higher in the IE than in the non-IE infections group. TNF-α and IL-12 levels were higher in staphylococcal IE than in the non-staphylococcal IE subgroup. There was a higher proportion of both low IL-10 producers and high producers of IL-1ß, TNF-α and IL-12 in the staphylococcal IE than in the non-staphylococcal IE subgroup. This study reinforces a relationship between the expression of proinflammatory cytokines, especially IL-1ß, IL-12 and TNF-α, and the pathogenesis of IE. A lower production of IL-10 and impairment in cytokine network may reflect the severity of IE and may be useful for risk stratification.

Usefulness of thrombocytopenia at admission as a prognostic marker in native valve left-sided infective endocarditis.

In-hospital mortality of patients with infective endocarditis (IE) remains exceedingly high. Quick recognition of parameters accurately identifying high-risk patients is of paramount importance. The objective of this study was to analyze the incidence and severity of thrombocytopenia at presentation and its prognostic impact in patients with native valve left-sided IE. We studied a cohort of 533 consecutive episodes of native valve left-sided IE prospectively recruited. We distinguished 2 groups: group I (n = 175), episodes who had thrombocytopenia at admission, and group II (n = 358) gathered all the episodes who did not. Thrombocytopenia at admission was defined as a platelet count of <150,000/µl. No differences were found in the need for surgery, but in-hospital mortality was significantly higher in patients with thrombocytopenia (p <0.001). Mortality rate was associated with the degree of thrombocytopenia (p <0.001). In the multivariable analysis, thrombocytopenia at admission was an independent predictor of higher mortality (p = 0.002). A synergistic interaction between thrombocytopenia and Staphylococcus aureus on mortality risk was also observed (p = 0.04). In conclusion, thrombocytopenia at admission is an early risk marker of increased mortality in patients with native valve left-sided IE. Mortality rates increased with increasing severity of thrombocytopenia. Thrombocytopenia at admission should be used as an early marker for risk stratification in patients with native valve IE to identify those at risk of complicated in-hospital evolution and increased mortality.

Infective endocarditis caused by Scedosporium prolificans infection in a patient with acute myeloid leukemia undergoing induction chemotherapy.

Disseminated Scedosporium prolificans infection occurs mainly in immunocompromised patients. The mortality rate is high, as the fungus is resistant to most antifungal agents. Here, we present the case of a 66-year-old female with acute myeloid leukemia who developed infective endocarditis caused by S. prolificans infection during induction chemotherapy. Her 1,3-ß-D-glucan levels were elevated and computed tomography revealed bilateral sinusitis and disseminated small nodular masses within the lungs and spleen; it nonetheless took 6 days to identify S. prolificans by blood culture. The patient died of multi-organ failure despite the combined use of voriconazole and terbinafine. Autopsy revealed numerous mycotic emboli within multiple organs (caused by mitral valve vegetation) and endocarditis (caused by S. prolificans). The geographic distribution of this infection is limited to Australia, the United States, and southern Europe, particularly Spain. The first Japanese case was reported in 2011, and four cases have been reported to date, including this one. Recently, the incidence of S. prolificans-disseminated infection in immunocompromised patients has increased in Japan. Therefore, clinicians should consider S. prolificans infection as a differential diagnosis when immunocompromised patients suffer disseminated infections with elevated 1,3-ß-D-glucan levels.