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Background. Blood culture-negative endocarditis (BCNE) may account for up to 31% of all cases of endocarditis. Methods. We used a prospective, multimodal strategy incorporating serological, molecular, and histopathological assays to investigate specimens from 819 patients suspected of having BCNE. Results. Diagnosis of endocarditis was first ruled out for 60 patients. Among 759 patients with BCNE, a causative microorganism was identified in 62.7%, and a noninfective etiology in 2.5%. Blood was the most useful specimen, providing a diagnosis for 47.7% of patients by serological analysis (mainly Q fever and Bartonella infections). Broad-range polymerase chain reaction (PCR) of blood and Bartonella-specific Western blot methods diagnosed 7 additional cases. PCR of valvular biopsies identified 109 more etiologies, mostly streptococci, Tropheryma whipplei, Bartonella species, and fungi. Primer extension enrichment reaction and autoimmunohistochemistry identified a microorganism in 5 additional patients. No virus or Chlamydia species were detected. A noninfective cause of endocarditis, particularly neoplasic or autoimmune disease, was determined by histological analysis or by searching for antinuclear antibodies in 19 (2.5%) of the patients. Our diagnostic strategy proved useful and sensitive for BCNE workup. Conclusions. We highlight the major role of zoonotic agents and the underestimated role of noninfective diseases in BCNE. We propose serological analysis for Coxiella burnetii and Bartonella species, detection of antinuclear antibodies and rheumatoid factor as first-line tests, followed by specific PCR assays for T. whipplei, Bartonella species, and fungi in blood. Broad-spectrum 16S and 18S ribosomal RNA PCR may be performed on valvular biopsies, when available.

BackgroundSince March 2020, health care systems were importantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, with some patients presenting severe acute respiratory distress syndrome (ARDS), requiring extra-corporeal membrane oxygenation (ECMO). We designed an ambispective observational cohort study including all consecutive adult patients admitted to 5 different ICUs from a university hospital. The main objective was to identify the risk factors of severe COVID-19 ARDS patients supported by ECMO associated with 90-day survival.ResultsBetween March 1st and November 30th 2020, 76 patients with severe COVID-19 ARDS were supported by ECMO. Median (interquartile range IQR) duration of mechanical ventilation (MV) prior to ECMO was of 6 (3–10) days. At ECMO initiation, patients had a median PaO2:FiO2 of 71 mmHg (IQR 62–81), median PaCO2 of 58 mmHg (IQR 51–66) and a median arterial pH of 7.33 (IQR 7.25–7.38). Forty-five patients (59%) were weaned from ECMO. Twenty-eight day, 60-day and 90-day survival rates were, respectively, 92, 62 and 51%. In multivariate logistic regression analysis, with 2 models, one with the RESP score and one with the PRESERVE score, we found that higher BMI was associated with higher 90-day survival [odds ratio (OR): 0.775 (0.644–0.934), p = 0.007) and 0.631 (0.462–0.862), respectively]. Younger age was also associated with 90-day survival in both models [OR: 1.1354 (1.004–1.285), p = 0.044 and 1.187 (1.035–1.362), p = 0.014 respectively]. Obese patients were ventilated with higher PEEP than non-obese patients and presented slightly higher respiratory system compliance.ConclusionIn this ambispective observational cohort of COVID-19 severe ARDS supported by ECMO, obesity was an independent factor associated with improved survival at 90-day.

ObjectiveTo assess long-term outcomes and predictors of mortality in patients treated according to current recommendations for cardiac implantable electronic device (CIED) infection.DesignTwo-group matched cohort study.SettingTertiary-care institution.PatientsConsecutive patients admitted for CIED infection between 2004 and 2008 were prospectively enrolled. Study subjects were matched to a cohort of uninfected CIED patients by age, sex and type of device.InterventionsIn all infected patients, the therapeutic approach consisted of complete hardware removal whenever possible, antimicrobial therapy, and implantation of a new device, if indicated. Patients were systematically followed, with standardised outcomes assessment.Main outcome measuresAll-cause mortality and predictors of long-term mortality.Results197 patients were included and matched 1:1 to controls. Pocket infections were present in 41.1% and definite or suspected infective endocarditis in 58.9%. Total or subtotal hardware removal was achieved in 98.5% of cases. Median follow up was 25 months (12–70). Mortality rates in the study group and controls were 14.3% vs 11.0% (NS) at 1 year and 35.4% vs 27.0% (p=NS) at 5 years. Independent predictors of long-term mortality were older age (HR=1.09, p<0.001), cardiac resynchronisation therapy (HR=3.70, p=0.001), thrombocytopenia (HR=5.10, p=0.003) and renal insufficiency (HR=2.66, p=0.006). In patients with reimplanted devices, epicardial right ventricular pacemakers were associated with higher mortality (HR=2.85, p=0.034).ConclusionIn patients with CIED infection managed by recommended therapy, long-term mortality rates are similar to comparable controls. Independent predictors include patient and disease-related factors, in addition to implantation of right ventricular epicardial pacemakers.

Background: Olmesartan-induced enteropathy is a rare complication of a widely used angiotensin II receptor blocker. Patients usually present with chronic diarrhea and weight loss. Histologically, villous atrophy and intraepithelial lymphocyte infiltrates within the duodenum confirm the diagnosis. The prognosis is usually good after withdrawal of the offending drug. Case presentation: Here, we report the case of a 76-year-old woman who developed a severe form of Olmesartan-induced enteropathy complicated by acute kidney injury and acute recurrence after drug rechallenge. After definite cessation of the drug, the patient did not experience any gastrointestinal (GI) symptom recurrence after 6 months of follow-up. However, she experienced chronic kidney disease stage G3b. Histological analysis did not show any villous atrophy or intraepithelial lymphocyte infiltrates within the duodenum or the colon biopsy. Discussion and conclusion: This case highlights the broad spectrum of clinical manifestations and histological findings in Olmesartan-induced enteropathy. It also highlights the importance of rapid diagnosis in order to limit organ damage such as chronic kidney disease.

Coxiella burnetii cardiovascular prosthetic infections are associated with high morbidity and mortality and represent a major health problem due to the lack of standardized management. We were confronted with a C. burnetii infection on Bentall-De Bono prosthesis characterized by a history of vascular infection with relapse that prompted us to screen for cases of C. burnetii on Bentall-De Bono vascular prosthesis monitored in our center. We screened patients between 1991 and 2019, from the French national reference center for Q fever. A microbiological criterion in addition to a lesional criterion was necessary to diagnose C. burnetii persistent vascular infection. Two thousand five hundred and eighty two patient were diagnosed with Coxiella burnetii infection and 160 patients with persistent C. burnetii vascular infection prosthesis, 95 of whom had a vascular prosthesis, including 12 with Bentall-De Bono prosthesis. Among patients with persistent C. burnetii prosthetic vascular infection, patients with Bentall-De Bono prostheses were significantly more prone to develop complications such as aneurysm, fistula, and abscess (62 versus 32%, two-sided Chi-square test, p = 0.04). All but one patient were treated with doxycycline and hydroxychloroquine for a mean (± standard deviation) period of 29.4 ± 13.6 months. Among the 12 patients, 5 had cardio-vascular complications, and 5 had prolonged antibiotherapy with doxycycline and hydroxychloroquine. Patients with C. burnetii vascular infection on Bentall-De Bono tend to be at high risk of developing complications (fistula, aneurysm, abscess, death). Surgery is rarely performed. Clinical, serological, and PET scanner imaging follow-up is recommended.

ObjectiveTo describe the characteristics of infective endocarditis (IE) in octogenarians and assess their prognosis.MethodsPatients with definite IE hospitalised at a referral centre between July 2008 and July 2013 were prospectively included. A total of 454 patients were divided into three groups: 230 patients under 65 years old, 173 patients between 65 and 80 years old, and 51 patients over 80 years old. The main end point was 1-year mortality.ResultsOne-year mortality was higher in the ≥80 years old group (37.3%) than in the <65 years old group (13%; p<0.001) and the 65–80 years old group (19.7%; p=0.009). Enterococci and Streptococcus gallolyticus were the more frequent micro-organisms. Embolism under antibiotic therapy (n=11 (21.6%), p=0.03) and renal failure (n=23 (51%), p=0.004) were more frequent in the ≥80 years old group. Among the ≥80 years old group, 38 patients had theoretical indication for surgery. Mortality was low (6.3%) in the 16 operated patients, but very high (72.7%) in the 22 patients not operated. Even if octogenarians were less often operated, their survival after surgery was excellent like younger patients (93.7%, 89.9% and 90.4%, respectively), whereas the absence of surgery was associated with very poor prognosis.ConclusionsIE in octogenarians is a different disease, with Enterococci as the most frequent micro-organisms and with higher mortality than younger patients. ESC recommendations for surgery are less implemented than in younger patients, yielding dramatic mortality in patients not operated despite a theoretical indication for surgery, while operated patients have an excellent prognosis. These results suggest that surgery is underused in octogenarians.

Background: Arteriovenous fistula (AVF) is the preferred vascular access option for hemodialysis (HD). The latter requires a remodeling process called maturation that can take up to 3 months. Maturation failure is a frequent complication associated with significant morbidity. The prevalence of antiphospholipid antibody (aPL) positivity in HD patients is high and may result in thrombosis of the vascular access. Recently, aPL persistent positivity has been associated with AVF maturation failure in a retrospective study including 116 patients. Methods: We are conducting an observational prospective cohort study aiming to evaluate this association. Included patients are planned for AVF creation, aged over 18 years old, and have an interpretable aPL assay confirmed at 12 weeks and without any other innate or acquired thrombophilia or inflammatory disease. Primary endpoints will be the evaluation of AVF maturation clinically and by ultrasound. Secondary endpoints will focus on clinical outcomes other than AVF maturation (i.e., primary patency, thrombosis or stenosis, bleeding and hemodialysis adequacy parameters). Conclusions: This prospective observational cohort study aims to examine the possibly causative link between aPL persistent positivity and AVF maturation failure. This study was registered on ClinicalTrials.gov (ID number: NCT06112821).

Introduction: Endothelial dysfunction is a common feature of end-stage kidney disease, requiring hemodialysis (HD) and antiphospholipid antibody (aPL) persistent positivity. Endothelial dysfunction can be assessed with noninvasive tests such as flow-mediated dilation (FMD). In the HD population, it is not known whether aPL persistent positivity is associated with a more severe endothelial dysfunction. Methods: We performed a cross-sectional study in our HD patients. The FMD of the brachial artery was measured in 17 aPL-positive patients who fulfilled the inclusion criteria and were matched to 17 controls according to age, gender, diabetes mellitus, smoking status and markers of dialysis adequacy (Kt/V). Results: FMD was significantly lower in the aPL group with a mean of 6.9% and 11.8% in the aPL-positive and the control groups, respectively (mean difference (IC 95%): −4.9 (−8.3; −1.6), p = 0.006). aPL was associated with a higher c-reactive protein level, and longer HD vintage. There was no statistical difference between groups in terms of pre-dialysis urea and urinary output, dialysis adequacy (Kt/V), and history of cardiovascular disease or treatments. Conclusions: aPL persistent positivity in HD patients was associated with worse endothelial dysfunction, reflected by FMD measurements. These findings have to be confirmed in larger studies.

Although bicuspid aortic valve (BAV) is one of the most common congenital heart diseases, clinical data associated with valve dysfunction are still limited. We evaluated clinical characteristics and echocardiography of French patients with BAV associated with leaking and stenosis degeneration. We initiated a prospective registry from 2014 to 2018 at a tertiary center. A total of 223 patients (168 males [75%], age 53 ± 17 years) were enrolled. Among these patients 83% had left–right coronary cusps fusion, 80% Sievers type 1 BAV and 49% showed aortic dilatation. Twenty-four patients (11%) had normal valve function, 66 patients (31%) had aortic stenosis (AS), 91 patients (41%) had aortic regurgitation (AR) and 40 patients (17%) had AR and AS. BAV phenotype did not predict neither AS nor AR (all p > 0.1). By multivariable analysis, age > 50 (41.6[10.3–248.2], p < 0.001) and presence of raphe/fusion (12.8[2.4–87.4], p < 0.001) were significantly associated with AS, whereas male gender was associated with AR (5[1.6–16.4], p = 0.005). In addition, leaking degeneration was observed at a much younger age than stenosis (44 ± 14 years vs. 66 ± 10 years, p < 0.01) and among patients with valve dysfunction younger age was independently associated with AR (1.9[1.85–1.94], p < 0.001). In this study we confirmed high prevalence of valve dysfunction at first diagnosis of BAV in a referred population. The degenerative process differs according to type of dysfunction and is mainly dependent on age and gender.

The arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. AVF stenosis is a common complication, often requiring balloon angioplasty. For recurrent stenosis, AVF stenting may be an option. Persistent antiphospholipid antibody (aPL) positivity is frequently observed in hemodialysis (HD) patients and is associated with AVF thrombosis and stenosis. This study aimed to evaluate AVF stent survival without stenosis in aPL-positive hemodialysis patients. A monocentric retrospective observational study was conducted on 35 patients who underwent AVF stenting between 1st January 2014 and 31st December 2023. The patients were divided into two groups: the aPL+ group [defined by a score of 3 or more based on the laboratory criteria of the 2023 ACR/EULAR for antiphospholipid syndrome (APS)] and the control group. Intrastent restenosis was defined as a chronic change in the AVFphysical examination or blood flow, confirmed by ultrasound (US) or angiography. Kaplan-Meier survival analysis was used to estimate the probability of stent survival without restenosis. The prevalence of intrastent restenosis was significantly higher in the aPL+ group at 24 months. The Kaplan-Meier survival analysis showed a significantly lower probability of AVF stent survival without restenosis in the aPL+ group (age-adjusted Hazard Ratio, 2.13 [IC95%, 1.70-2.69]). To the best of our knowledge, we describe for the first time a statistically significant association between aPL+ and AVF intrastent restenosis. Intimal hyperplasia is a non-thrombotic lesion associated with aPL+ and is linked to the mammalian target of rapamycin (mTOR) signaling pathway. We hypothesize that aPL may contribute to intrastent restenosis by inducing intimal hyperplasia. Whether this phenomenon is mTOR-mediated and whether sirolimus-eluting stents or balloons could be a better option for aPL+ patients requires further study.