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Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: B. G. reports receipt of nonfinancial support from Gilead Sciences, MSD, and Pfizer outside the submitted work. F. R. reports receipt of personal fees from AbbVie, AstraZeneca, Gilead Sciences, Janssen, Merck, Roche, and ViiV Healthcare outside the submitted work. E. C. reports personal fees from GILEAD, SANOFI-GENZYME, and BAXTER outside the submitted work. B. T. reports receipt of nonfinancial support from Gilead Sciences and personal fees from AbbVie, Gilead Sciences, Lilly Oncology, and Incyte outside the submitted work. None declared (R. Lécuyer, N. I., F. C., R. Lavergne, F. G., F. M., D. B., A. C., M. G., Y. C., A. N.).

Background: Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated., Research Question: Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease?, Study Design and Methods: In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to the European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality., Results: Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95% CI, 2.16-14.1; P < .001), IMIDs (OR, 2.19; 95% CI, 1.05-4.60; P = .037), long-term corticosteroid exposure (OR, 2.07; 95% CI, 1.03-4.31; P = .045), cysts in sputum/BAL smears (OR, 1.92; 95% CI, 1.02-3.62; P = .043), and SOFA score at admission (OR, 1.58; 95% CI, 1.39-1.82; P < .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95% CI, 1.03-2.71; P = .035), especially for a prednisone daily dose ≥ 10 mg (OR, 1.80; 95% CI, 1.14-2.85; P = .010)., Interpretation: Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: B. G. reports receipt of nonfinancial support from Gilead Sciences, MSD, and Pfizer, outside the submitted work. F. R. reports receipt of personal fees from Abbvie, Astra Zeneca, Gilead Sciences, Janssen, Merck, Roche, and ViiV Healthcare, outside the submitted work. E. C. reports personal fees from Gilead, Sanofi-Genzyme, and Baxter, outside the submitted work. None declared (R. L., N. I., F. C., R.-a. L., F. G., F. M., D. B., A. C., M. G., Y. C., A. N., B. T.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study aims to assess the safety, virological, and clinical outcomes of convalescent plasma transfusion (CPT) in immunocompromised patients hospitalized for coronavirus disease 2019 (COVID-19). We conducted a retrospective multicenter cohort study that included all immunosuppressed patients with COVID-19 and RNAemia from May 2020 to March 2023 treated with CPT. We included 81 patients with hematological malignancies (HM), transplants, or autoimmune diseases (69% treated with anti-CD20). Sixty patients (74%) were vaccinated, and 14 had pre-CPT serology >264 BAU/mL. The median delay between symptom onset and CPT was 23 days [13-31]. At D7 post-CPT, plasma PCR was negative in 43/64 patients (67.2%), and serology became positive in 25/30 patients (82%). Post-CPT positive serology was associated with RNAemia negativity (p < 0.001). The overall mortality rate at D28 was 26%, being higher in patients with non-B-cell HM (62%) than with B-cell HM (25%) or with no HM (11%) (p = 0.02). Patients receiving anti-CD20 without chemotherapy had the lowest mortality rate (8%). Positive RNAemia at D7 was associated with mortality at D28 in univariate analysis (HR: 3.05 [1.14-8.19]). Eight patients had adverse events, two of which were severe but transient. Our findings suggest that CPT can abolish RNAemia and ameliorate the clinical course in immunocompromised patients with COVID-19., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Infective endocarditis (IE) is increasingly affecting older patients. However, data on their management are sparse, and the benefits of surgery in this population are unclear., Methods: We included patients with left-sided IE (LSIE) aged ≥ 80 years enrolled in a prospective endocarditis cohort managed in Aquitaine, France, from 2013 to 2020. Geriatric data were collected retrospectively to identify factors associated with the 1-year risk of death using Cox regression., Results: We included 163 patients with LSIE (median age, 84 years; men, 59%; rate of prosthetic LSIE, 45%). Of the 105 (64%) patients with potential surgical indications, 38 (36%) underwent valve surgery: they were younger, more likely to be men with aortic involvement, and had a lower Charlson comorbidity index. Moreover, they had better functional status at admission (ie, the ability to walk unassisted and a higher median activities of daily living [ADL] score; n = 5/6 vs 3/6, P = .01). The 1-year mortality rate in LSIE patients without surgical indications was 28%; it was lower in those who were operated on compared with those who were not despite a surgical indication (16% vs 66%, P < .001). Impaired functional status at admission was strongly associated with mortality regardless of surgical status. In patients unable to walk unassisted or with an ADL score <4, there was no significant surgical benefit for 1-year mortality., Conclusions: Surgery improves the prognosis of older patients with LSIE and good functional status. Surgical futility should be discussed in patients with altered autonomy. The endocarditis team should include a geriatric specialist., Competing Interests: Potential conflicts of interest . F. B. reports research grants from Gilead and ViiV Healthcare and payments for educational events from Gilead, ViiV Healthcare, and MSD. The remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Gaucher disease type 1 (GD1) is a rare genetic lysosomal storage disorder. Eliglustat is a first-line oral therapy for adult patients with GD1. The aim of the ELIPRO (ELIglustat Patient Reported Outcomes) study was to assess real-world outcomes of eliglustat treatment for over 1 year in patients with GD1, with a focus on patient-reported outcomes (PROs), including treatment adherence., Methods: This was a non-interventional, prospective, multicentric study. Patients were stratified according to their previous time on eliglustat: >6 months (Group1) and ≤ 6 months (Group2). The primary endpoint was adherence to eliglustat, measured by the eight-items Morisky Medication Adherence Scale (MMAS-8; scale of 0-8) at 6 months in Group2. Secondary endpoints were quality of life (QoL) measured by patient input using the European Quality of Life five-dimensional three-level [EQ-5D-3L] questionnaire, fatigue and pain measured by numeric rating scale [NRS; on a scale of 0-10], the evaluation of patient satisfaction level regarding eliglustat treatment measured by Likert scale [scale of 0-7] and treatment adherence at 12 months in both groups. The study also evaluated the safety and effectiveness of eliglustat in the adult GD1 population., Results: Sixty patients with GD1 (approximatively 52% male, mean age: 46.6 ± 13.9 years) were analyzed: 29 in Group1 and 31 in Group2. GD1 was mostly of mild severity (90%) and 95% of patients had extensive CYP2D6 metabolizer phenotype. Fifty-seven patients had previously received treatment for GD1 (91% enzyme replacement therapy) and 15% were splenectomized. Groups1 and 2 were not necessarily matching for all characteristics. At 6 months, 58% of Group2 patients showed medium adherence (6 < MMAS-8 < 7.75) while 21% showed high adherence (MMAS-8: 8) (mean MMAS-8: 6.7 ± 1.0); similar results were obtained in Group1 (50% showed high compliance, 35% showed medium compliance; mean MMAS-8: 6.8 ± 1.4). The mean MMAS-8 for Group1 and Group2 were 7.1 ± 1.2 (vs 7.0 ± 1.0 at baseline) and 6.5 ± 1.0, respectively, at 12 months. At 12 months, the mean NRS scores in Group1 and Group2 were 72.0 ± 18.5 and 77.3 ± 13.7 for QoL (vs. 71.7 ± 18.4 and 80.2 ± 12.4, respectively at baseline), 4.8 ± 2.6 and 3.6 ± 2.7 for fatigue (vs. 4.6 ± 2.7 and 3.6 ± 2.6, respectively at baseline) and 3.3 ± 2.7 and 2.3 ± 2.3 for pain (vs. 3.3 ± 2.7 and 2.0 ± 2.4, respectively at baseline). GD1 assessments (biological, clinical and imaging parameters) remained stable during 12 months in both groups. At the end of the study, majority (97.4%) of patients were satisfied with their treatment with eliglustat (satisfaction score over 5 out of 7). Sixty-six percent of patients (n = 41) experienced mostly mild adverse events (AE) (including four study withdrawals), of whom 27.4% (n = 17) of patients experienced eliglustat-related AEs. Treatment adherence remained stable during 12 months in both groups., Conclusions: Eliglustat treatment compliance was good and sustained, along with overall health state, fatigue and pain levels, which was consistent with overall patients' clinical status. Eliglustat was well tolerated, and had a good safety profile, aligned with a good patient satisfaction. Our study should encourage greater use of PROs for evaluation of impact of the GD treatment on patient's symptoms and well-being., Competing Interests: Declaration of Competing Interest Fabrice CAMOU: consultancies with Sanofi, Takeda, AstraZeneca, Gilead, Pfizer; Scientific Advisory Boards for Sanofi, Pfizer. Angela COUTINHO: consultancies with Amicus Therapeutics, Orchard, Orphazyme and Sanofi. Marc G. BERGER: consultancies with Sanofi, Takeda, Pfizer, Novartis; Scientific Advisory Boards for Sanofi, Takeda, Pfizer, Novartis; GHI: research grants from Pfizer. Bérengère CADOR-ROUSSEAU: consultancies with Sanofi, Amicus, and Takeda. Francis GACHES: consultancies with Sanofi and Novartis; Scientific Advisory Boards for Sanofi. Nadia BELMATOUG: consultancies with Sanofi, Takeda; Scientific Advisory Boards for Sanofi, Takeda; Medical Advisory Boards for Sanofi, Takeda. GHI: research grants from Sanofi, Takeda; Expert testimony to Sanofi, Takeda; Steering Committee for Sanofi, Takeda; Fees for serving on Steering and Data Monitoring Committees from Sanofi, Takeda. Audrey LAGADEC: Employees of Sanofi, may hold shares and/or stock options in the company., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: F. Camou déclare avoir participé à des interventions ponctuelles pour les entreprises Gilead, Novartis, Pfizer et avoir été pris en charge, à l’occasion de déplacements pour congrès, par Novartis, Pfizer, Sanofi.

Objectives: Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19., Design: FOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study., Setting: Twelve clinical sites in France (ICU and general hospitals)., Patients: Patients receiving greater than or equal to 5 L oxygen/min to maintain Sp o2 greater than 93% (World Health Organization scale ≥ 5). Patients received conventional oxygen therapy or high-flow oxygen (HFO)/noninvasive ventilation (NIV) in cohort 1; HFO, NIV, or invasive mechanical ventilation (IMV) in cohort 2; and IMV in cohort 3., Interventions: Patients were randomly assigned, in a 1:1 ratio, to receive avdoralimab or placebo. The primary outcome was clinical status on the World Health Organization ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2., Measurements and Main Results: We randomized 207 patients: 99 in cohort 1, 49 in cohort 2, and 59 in cohort 3. During hospitalization, 95% of patients received glucocorticoids. Avdoralimab did not improve World Health Organization clinical scale score on days 14 and 28 (between-group difference on day 28 of -0.26 (95% CI, -1.2 to 0.7; p = 0.7) in cohort 1 and -0.28 (95% CI, -1.8 to 1.2; p = 0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of -6.3 (95% CI, -13.2 to 0.7; p = 0.96) or secondary outcomes in any cohort. No subgroup of interest was identified., Conclusions: In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 and 28 (funded by Innate Pharma, ClinicalTrials.gov number, NCT04371367)., Competing Interests: Dr. Carvelli received support for article research from Innate Pharma. Drs. Carvelli, Allardet-Servent, Barbar, Desgrouas, Camou, Piperoglou, Viotti, Boyer-Chammard, Lacombe, Le Dault, Schleinitz, and Vivier disclosed the off-label product use of avdoralimab. Dr. Guervilly received funding from Xenios FMC. Dr. Demaria’s institution received funding from BPI. Drs. Demaria, Karakunnel, Fares, Batista, Boyer-Chammard, and Vivier received funding from innate pharma. Drs. Demaria, Karakunnel, Fares, Batista, Rotolo, Viotti, Boyer-Chammard, and Vivier disclosed that they are employees of Innate Pharma. Dr. Karakunnel received funding from Primevax Precision Biologics. Dr. Rotolo received funding from Sanofi. Dr. Viotti disclosed work for hire. Dr. Lacombe received funding from MSD, Gilead, Janssen, and ViiV Healthcare. Dr. Vivier disclosed that he is a cofounder, shareholder, and employee of Innate Pharma and that his spouse is a shareholder of Innate Pharma. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: Dexamethasone and tocilizumab are used to treat severely ill COVID-19 patients admitted to intensive care units (ICUs). We explored whether combination therapy increased the risk of superinfection compared to dexamethasone alone., Methods: This observational, retrospective study included critically ill COVID-19 adult patients admitted to our ICU because of respiratory failure. Patients received dexamethasone with (Group 1) or without (Group 2) tocilizumab. Data were collected from electronic medical files., Results: A total of 246 patients were included, of whom 150 received dexamethasone and tocilizumab, while 96 received dexamethasone alone. Acute respiratory distress syndrome was evident on admission in 226 patients, 56 of whom required mechanical ventilation (MV). Superinfections, mainly respiratory, were diagnosed in 59 patients, including 34/150 (23%) in Group 1 and 25/96 (26%) in Group 2 ( p = 0.32). After multivariate analysis, the factors associated with a higher risk of superinfection included hematological malignancy (hazard ratio (HR): 2.47 (1.11-5.47), p = 0.03), MV (HR: 3.74 (1.92-7.26), p = 0.0001), and a higher SAPS-II score on admission (HR: 1.03 (1.01-1.06), p = 0.006)., Conclusion: In critically ill COVID-19 patients, the addition of tocilizumab to dexamethasone was not associated with an increased risk of superinfection.

Background: The role of respiratory coinfections at diagnosis of Pneumocystis jirovecii pneumonia (PcP) on clinical impact has been underestimated., Methods: A retrospective observational study was conducted January 2011 to April 2019 to evaluate respiratory coinfections at diagnosis of PcP patients in 2 tertiary care hospitals. Coinfection was defined by identification of pathogens from P. jirovecii-positive samples., Results: Of 7882 respiratory samples tested for P. jirovecii during the 8-year study, 328 patients with diagnosis of PcP were included. Mean age was 56.7 (SD 14.9) years, 193 (58.8%) were male, 74 (22.6%) had positive HIV serology, 125 (38.1%) had viral coinfection, 76 (23.2%) bacterial coinfection, and 90-day mortality was 25.3%. In the overall population, 90-day mortality was independently associated with solid tumor underlying disease (odds ratio [OR], 11.8; 95% confidence interval [CI], 1.90-78.0; P = .008), sepsis-related organ failure assessment score (SOFA) at admission (OR, 1.62; 95% CI, 1.34-2.05; P< .001), and cytomegalovirus (CMV) respiratory coinfection (OR, 3.44; 95% CI, 1.24-2.90; P = .02). Among HIV-negative patients, respiratory CMV coinfection was associated with worse prognosis, especially when treated with adjunctive corticosteroid therapy., Conclusions: Respiratory CMV coinfection at PcP diagnosis was independently associated with increased 90-day mortality, specifically in HIV-negative patients., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Little data is available on extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) rectal colonization in cancer patients admitted to the intensive care unit (ICU). We aimed to describe the epidemiology of ESBL-E in cancer patients hospitalized in the ICU compared with non-cancer patients. ESBL-E colonization was detected in 6.6% of 1,013 cancer patients and 6.4% of 1625 non-cancer patients. At admission, among the 172 colonized patients: 48/67 cancer patients and 78/105 non-cancer patients developed an infection, documented with an ESBL-E for 21% and 24% of them, respectively. The in-hospital mortality rate among colonized patients was 33% in cancer patients and 12% in non-cancer patients. In cancer patients, ESBL-E infections are rare but systematic rectal screening identifies high-risk population and guides empirical antibiotic therapy. It also contributes to being aware of the ICU microbiological ecology., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objectives: The aim of this study was to assess the diagnostic performances of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) in congenital heart disease (CHD) patients with pulmonary prosthetic valve or conduit endocarditis (PPVE) suspicion., Background: PPVE is a major issue in the growing CHD population. Diagnosis is challenging, and usual imaging tools are not always efficient or validated in this specific population. Particularly, the diagnostic yield of 18 F-FDG PET/CT remains poorly studied in PPVE., Methods: A retrospective multicenter study was conducted in 8 French tertiary centers. Children and adult CHD patients who underwent 18 F-FDG PET/CT in the setting of PPVE suspicion between January 2010 and May 2020 were included. The cases were initially classified as definite, possible, or rejected PPVE regarding the modified Duke criteria and finally by the Endocarditis Team consensus. The result of 18 F-FDG PET/CT had been compared with final diagnosis consensus used as gold-standard in our study., Results: A total of 66 cases of PPVE suspicion involving 59 patients (median age 23 years, 73% men) were included. Sensitivity, specificity, positive predictive value, and negative predictive value of 18 F-FDG PET/CT in PPVE suspicion were respectively: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%). 18 F-FDG PET/CT findings would help to correctly reclassify 57% (4 of 7) of possible PPVE to definite PPVE., Conclusions: Using 18 F-FDG PET/CT improves the diagnostic accuracy of the Duke criteria in CHD patients with suspected PPVE. Its high positive predictive value could be helpful in routine to shorten diagnosis and treatment delays and improve clinical outcomes., Competing Interests: Funding Support and Author Disclosures Drs Venet, Jalal, and Thambo were supported by the French Government as part of the “Investments of the future” program managed by the National Research Agency (grant reference ANR-10-IAHU-04). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Within the context of the wide use of fluoroquinolones (FQs) and the emergence of multidrug-resistant bacteria, French recommendations concerning the appropriate use of systemic FQs in adults were published in 2015. This study assessed the impact of antibiotic stewardship intervention on the use of FQs over a 5-year period., Methods: Five annual audits were performed to evaluate FQ prescriptions. Following the baseline audit, a campaign of appropriate antibiotic use was initiated with courses on antibiotics including FQs. All audits included quantitative and qualitative evaluations to calculate an index of therapeutic adequacy (ITA) with six criteria: indication, molecule type, dosage, duration, route of administration and association. These audits were performed annually from 2015 to 2019., Key Findings: The number of prescriptions decreased substantially from 90 in 2015 to 17 in 2019. This reduction was consistent with consumption data, such that the defined daily dose for 1000 bed days diminished from 67 in 2015 to 42 in 2019. Between 2015 and 2016, the ITA decreased significantly from 3.27 to 1.79 (P = 0.001), corresponding to an improvement in prescription quality. The ITA stabilised between 2016 and 2019. Moreover, improvements were observed in the proportion of entirely conforming prescriptions, conformity of indications, choice of molecule type among FQs and proportion of prescriptions with non-conforming treatment durations., Conclusions: Between 2015 and 2019, we observed quantitative and qualitative improvements in FQ prescriptions within the hospital. Prescription follow-up through annual audits, combined with training courses, contributed to consistent results., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: High-resolution free-breathing late gadolinium enhancement (HR-LGE) was shown valuable for the diagnosis of acute coronary syndromes with non-obstructed coronary arteries. The method may be useful to detect COVID-related myocardial injuries but is hampered by prolonged acquisition times. We aimed to introduce an accelerated HR-LGE technique for the diagnosis of COVID-related myocardial injuries., Method: An undersampled navigator-gated HR-LGE (acquired resolution of 1.25 mm 3 ) sequence combined with advanced patch-based low-rank reconstruction was developed and validated in a phantom and in 23 patients with structural heart disease (test cohort; 15 men; 55 ± 16 years). Twenty patients with laboratory-confirmed COVID-19 infection associated with troponin rise (COVID cohort; 15 men; 46 ± 24 years) prospectively underwent cardiovascular magnetic resonance (CMR) with the proposed sequence in our center. Image sharpness, quality, signal intensity differences and diagnostic value of free-breathing HR-LGE were compared against conventional breath-held low-resolution LGE (LR-LGE, voxel size 1.8x1.4x6mm)., Results: Structures sharpness in the phantom showed no differences with the fully sampled image up to an undersampling factor of x3.8 (P > 0.5). In patients (N = 43), this acceleration allowed for acquisition times of 7min21s ± 1min12s at 1.25 mm 3 resolution. Compared with LR-LGE, HR-LGE showed higher image quality (P = 0.03) and comparable signal intensity differences (P > 0.5). In patients with structural heart disease, all LGE-positive segments on LR-LGE were also detected on HR-LGE (80/391) with 21 additional enhanced segments visible only on HR-LGE (101/391, P < 0.001). In 4 patients with COVID-19 history, HR-LGE was definitely positive while LR-LGE was either definitely negative (1 microinfarction and 1 myocarditis) or inconclusive (2 myocarditis)., Conclusions: Undersampled free-breathing isotropic HR-LGE can detect additional areas of late enhancement as compared to conventional breath-held LR-LGE. In patients with history of COVID-19 infection associated with troponin rise, the method allows for detailed characterization of myocardial injuries in acceptable scan times and without the need for repeated breath holds., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aims to assess the efficacy and safety of convalescent plasma therapy (CPT) in COVID-19 critically ill patients with protracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia. A retrospective cohort study was conducted in intensive care unit (ICU). All patients with severe COVID-19 pneumonia for whom RNAemia remained positive more than 14 days after onset of the infection were included and given CPT. The primary objective was to evaluate SARS-CoV-2 RNAemia 7 days (D7) after CPT. A total of 14 patients were included and they received a median CPT volume of 828 ml (range: 817-960). CPT was administered in a median time of 14 days after ICU admission. At D7, 13/14 patients had negative SARS-CoV-2 blood PCR and one patient had negative blood PCR 11 days after CPT. At D7 and at D14, the clinical status was improved in 7/14 and 11/14 patients, respectively. The 28-day mortality rate was 14%. No CPT-related adverse effects had been reported. CPT is safe and may be efficient in patients with protracted RNAemia admitted in ICU for severe COVID-19 pneumonia. Randomized controlled trials are needed to confirm these results., (© 2021 Wiley Periodicals LLC.)

Objectives: Current guidelines recommend cefazolin as an alternative to antistaphylococcal penicillins (ASPs) in methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis despite the lack of comparative study. The objective of this study was to evaluate the comparative outcomes of cefazolin vs. ASPs in MSSA infective endocarditis., Methods: This was a retrospective analysis of an observational multicentre cohort study using prospectively collected data from patients with MSSA endocarditis confirmed by endocarditis team and treated either with cefazolin or ASPs between July 2013 and December 2018. Patients were excluded if they received both treatments. The primary outcome was 90-day all-cause mortality., Results: Of 210 patients included, 53 patients (25.2%) received cefazolin and 157 (74.8%) received ASPs. The overall 90-day mortality rate was 27.6% (58/210 patients), 24.5% (13/53) in the cefazolin group vs. 28.7% (45/157) in the ASP group (p 0.561). Premature antimicrobial discontinuation due to adverse events occurred less frequently with cefazolin than with ASPs (0/53 vs. 13/157 patients; p 0.042). In multivariate analysis, there was no difference in 90-day mortality between cefazolin and ASPs (adjusted odds ratio (aOR), 1.2; 95% confidence interval (CI), 0.49-2.91; p 0.681), while age (aOR, 1.06; 95% CI, 1.03-1.09; p < 0.001), Charlson comorbidity index (aOR, 1.18; 95% CI, 1.02-1.36 p 0.023), cerebral embolism (aOR, 2.83; 95% CI, 1.33-6.14; p 0.007) and intensive care unit admission (aOR, 4.16; 95% CI, 1.89-9.59; p 0.001) were factors significantly associated with higher mortality., Conclusions: Cefazolin seems to be a possible alternative to ASPs in MSSA endocarditis. More studies are needed to confirm these results and determine which treatment should be recommended as first-line therapy., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin., Methods: This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients., Results: At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported., Conclusions: Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov.

Rationale & Objective: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction., Study Design: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines., Setting & Study Populations: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms., Selection Criteria for Studies: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI., Data Extraction: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis., Analytical Approach: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses., Results: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively., Limitations: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies., Conclusions: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Patients presenting with acute myeloid leukemia (AML) at diagnosis are at high risk of severe complications and death, particularly with high white blood cell (WBC) count. In this retrospective study, we evaluate interest of early and systematic support in the intensive care unit (ICU) for AML with hyperleukocytosis (AML-HL) at diagnosis., Methods: Patients with AML-HL, defined by WBC > 50 × 10 9 /L, primary referred in ICU ("Early ICU") without organ failure and before initiating chemotherapy induction were compared to patients first admitted in the Hematology Department who required a secondary transfer in ICU ("Late ICU") or not ("No ICU"). Primary end point was mortality during the first month, and secondary end points were the use of life-sustaining therapies in ICU and risk factors for ICU transfer and mortality., Results: One hundred fifty-four patients were included: 77 (50%) to the group "No ICU", 18 (12%) to "Late ICU" and 59 (38%) to "Early ICU". Mortality at day 30 was higher in "Late ICU" than in "Early ICU" and "No ICU", with 27.8%; 16.9% and 2.6% respectively (P < 0.001). "Late ICU" patients had an increased use of life-sustaining therapy comparing to "Early ICU" patients (56% vs. 29%, P = 0.04)., Conclusions: Early referral to ICU reduces morbidity and seems an effective strategy to reduce short-term mortality in AML-HL at diagnosis., Competing Interests: The authors have no conflict of interest to declare., (Copyright 2020, Mottal et al.)

Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2., (© 2020 by The American Society of Hematology.)

In nonoperated prosthetic valve endocarditis (PVE), long-term outcome is largely unknown. We report the follow-up of 129 nonoperated patients with PVE alive at discharge. At 1 year, the mortality rate was 24%; relapses and reinfection were rare (5% each). Enterococcal PVE was associated with a higher risk of relapse., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Patients with type 1 Gaucher disease (GD1) present thrombocytopenia, anemia, organomegaly, and bone complications. Most experts consider that the less aggressive forms do not require specific treatment. However, little is known about the disease course of these forms. The objective of this cross-sectional retrospective study was to compare the clinical, radiological, and laboratory characteristics of patients with less severe GD1 at diagnosis and at the last evaluation to identify features that might lead to potential complications. Non-splenectomized and never-treated patients (19 women and 17 men) were identified in the French Gaucher Disease Registry (FGDR). Their median age was 36.6 years (2.4-75.1), and their median follow-up was 7.8 years (0.4-32.4). Moreover, 38.7% were heterozygous for the GBA1 N370S variant, and 22.6% for the GBA1 L444P variant. From diagnosis to the last evaluation, GD1 did not worsen in 75% of these patients. Some parameters improved (fatigue and hemoglobin concentration), whereas platelet count and chitotriosidase level remained stable. In one patient (2.7%), Lewy body dementia was diagnosed at 46 years of age. Bone lesion onset was late and usually a single event in most patients. This analysis highlights the genotypic heterogeneity of this subgroup, in which disease could remain stable and even improve spontaneously. It also draws attention to the possible risk of Lewy body disease and late onset of bone complications, even if isolated, to be confirmed in larger series and with longer follow-up., Competing Interests: C.S., B.C., and I.B. received speaker fees from Shire International GmbH, now part of Takeda and Sanofi Genzyme. M.G.B. received speaker fees and research grants from Shire International GmbH, now part of Takeda. B.H. received speaker fees from Janssen and Sanofi. F.C. received speaker fees from Shire International GmbH, now part of Takeda and Sanofi Genzyme and is primary investigator for Sanofi Genzyme. J.S., A.B., N.B., C.C., T.B.V., F.D., R.F., A.M., A.B., L.S., Claire de Moreuil, B.C., I.D., V.L.S., S.H., L.A., S.P., I.H.R., Catherine Marcel, M.B., and K.Y. have no conflicts to declare.

Background: Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported., Methods: Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated., Results: Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12-23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54-140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 ± 20, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr >200 µmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively., Conclusion: Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Introduction: There is currently a lack of evidence for the relative effectiveness of partial resection (PR) and total resection (TR) before managing abdominal aortic graft infection (AGI). Most authorities agree that TR is mandatory for intracavitary AGI in patients with favorable conditions but there is an increasing number of patients with severe comorbidities for whom this approach is not suitable, resulting in a prohibitive mortality rate. The purpose of this study was to determine the most appropriate indication for TR or PR., Evidence Acquisition: A meta-analysis was conducted on the rates of early/late mortality, amputations and reinfection. A meta-regression was performed with eight variables: patient age, male prevalence, presence of virulent or nonvirulent organisms, urgency, omentoplasty and follow-up., Evidence Synthesis: Twenty-one studies and 1052 patients were included. For TR and PR, the rates of early mortality and reinfection were 16.8% and 10.5%, 11% and 27%, respectively. For TR urgency and male gender were associated with increased rate of early mortality and male gender, PDF and virulent organisms were associated with increased risk of reinfection. For PR no statistical correlation was analyzable except for PDF with increased risk of reinfection., Conclusions: Early mortality rates are higher for TR and reinfection rates are higher for PR. For TR early mortality increases in urgent cases and it is suggested that alternative option must be discussed, reinfection decreases in the presence of nonvirulent organisms and TR seems optimal. For TR and PR reinfection increases in presence of PDF and alternative technique may be more appropriate.

Objectives: In the last decades, the number of cancer patients admitted in intensive care units (ICUs) for septic shock has dramatically increased. However, prognosis data remain scarce., Methods: To assess the 180-day mortality rate in cancer patients admitted to the ICU for septic shock, a 5-year prospective study was performed. All adult patients admitted for septic shock were included and categorized into the following two groups and four subgroups: cancer patients (solid tumor or hematological malignancy) and non-cancer patients (immunocompromised or not). Data were collected and compared between the groups. Upon early ICU admission, the decision to forgo life-sustaining therapy (DFLST) or not was made by consultation among hematologists, oncologists, and the patients or their relatives., Results: During the study period, 496 patients were admitted for septic shock: 252 cancer patients (119 hematological malignancies and 133 solid tumors) and 244 non-cancer patients. A DFLST was made for 39% of the non-cancer patients and 52% of the cancer patients. The 180-day mortality rate among the cancer patients was 51% and 68% for those with hematological malignancies and solid cancers, respectively. The mortality rate among the non-cancer patients was 44%. In a multivariate analysis, the performance status, Charlson comorbidity index, simplified acute physiology score 2, sequential organ failure assessment score, and DFLST were independent predictors of 180-day mortality., Conclusions: Despite early admission to the ICU, the 180-day mortality rate due to septic shock was higher in cancer patients compared with non-cancer patients, due to excess mortality in the patients with solid tumors. The long-term prognosis of cancer patients with septic shock is modulated by their general state, severity of organ failure, and DFLST.

Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase; polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (> 30 vs. ≤30 years, HR 4.71, 95%CI [2.40-9.27]; p < 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.

Background: The absence of fever in bacteremia in patients who are older is known to delay diagnosis. Our objective was to determine whether atypical presentation was associated to mortality as a result of bacteremia in this patient cohort as well as possible factors associated with this atypical presentation., Methods: We conducted an observational prospective study in 2 French university hospitals in 2016-2017 including patients ages ≥75 years with bacteremia. Atypical presentation was defined as the absence of a temperature ≥38.3°C or <36°C, chills, or hypotension. Mortality and dependence for activities of daily living (ADL) were recorded at 1 week (D7) and 3 months (D90)., Results: Among the 151 patients (mean age 85.4±5.8 years) enrolled, atypical presentation prevalence was 21.2%. D7 and D90 mortality rates were 7.9% and 40.0%, respectively. Atypical presentation was independently associated with D7 (odds ratio (OR) 4.46, 95% confidence interval (CI) 1.04-19.24) and D90 mortality (OR 3.76, 95% CI 1.30-10.92) after controlling for other prognostic factors. Patients with diabetes and those infected with Staphylococcus aureus were more likely to have atypical signs of infection. ADL score decreased from 3.6±2.0 before bacteremia to 2.8±2.1 at D90 (P <0.001)., Conclusion: Patients who are older with bacteremia have poor vital and functional prognoses in the short and long terms. The absence of typical signs of infection is associated with mortality. Blood culture should be considered for patients who are older, especially with diabetes with acute unexplained clinical manifestations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft-tissue infections (SSTIs), but its real-life use is not well known. The aim of this study was to describe all first prescriptions in France over an 16-month period. A retrospective study on all adult patients receiving at least one dose of dalbavancin from 1 June 2017 to 31 September 2018 was performed (75 patients from 29 French hospitals). Data were collected via a standard questionnaire. Failure was defined as persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment, and/or death from infection. The main indications were bone and joint infection (BJI) (64.0%), endocarditis (25.3%), and SSTI (17.3%). The main bacteria involved were Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%), and coagulase-negative staphylococci (44.4%). Median minimum inhibitory concentrations (MICs) for staphylococci to vancomycin and dalbavancin ranged from 0.875-2.0 mg/L and 0.032-0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. The main treatment regimens for dalbavancin were a two-dose regimen (1500 mg each) in 38 cases (50.7%) and a single-dose regimen (1500 mg) in 13 cases (17.3%). Overall, at the patient's last visit, clinical cure was observed in 54/68 patients, whilst failure was observed in 14/68 patients. First use of dalbavancin in France was mostly off-label. Most were due to BJI, often as rescue therapy for severe infections. Even in off-label situations, dalbavancin appears safe and effective., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: In the management of infective endocarditis (IE), the presence of extracardiac complications has an influence on both diagnosis and treatment. Current guidelines suggest that systematic thoracoabdominal-pelvic computed tomography (TAP-CT) may be helpful. Our objective was to describe how systematic TAP-CT affects the diagnosis and the management of IE., Methods: In this multicenter cohort study, between January 2013 and July 2016 we included consecutive patients who had definite or possible IE according to the Duke modified criteria, validated by endocarditis teams. We analyzed whether the Duke classification and therapeutic management were modified regarding the presence or the absence of IE-related lesion on CT and investigated the tolerance of this examination., Results: Of the 522 patients included in this study, 217 (41.6%) had 1 or more IE-related lesions. On the basis of CT results in asymptomatic patients, diagnostic classification was upgraded from possible endocarditis to definite endocarditis for only 4 cases (0.8%). The presence of IE-related lesions on CT did not modify the duration of antibiotic treatment (P = .55), nor the decision of surgical treatment (P = .39). Specific treatment of the lesion was necessary in 42 patients (8.0%), but only 9 of these lesions (1.9%) were asymptomatic and diagnosed only on the TAP-CT. Acute kidney injury (AKI) within 5 days of CT was observed in 78 patients (14.9%)., Conclusions: The TAP-CT findings slightly affected diagnosis and treatment of IE in a very small proportion of asymptomatic patients. Furthermore, contrast media should be used with caution because of the high risk of AKI., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background and Objectives: Intravenous imiglucerase enzyme replacement therapy for Gaucher disease type 1 administered every 2 weeks is at variance with the imiglucerase plasma half-life of a few minutes. We hypothesized that studying the pharmacokinetics of imiglucerase in blood Gaucher disease type 1 monocytes would be more relevant for understanding enzyme replacement therapy responses., Methods: Glucocerebrosidase intra-monocyte activity was studied by flow cytometry. The pharmacokinetics of imiglucerase was analyzed using a population-pharmacokinetic model from a cohort of 31 patients with Gaucher disease type 1 who either started or were receiving long-term treatment with imiglucerase., Results: A pharmacokinetic analysis of imiglucerase showed a two-compartment model with a high peak followed by a two-phase exponential decay (fast phase half-life: 0.36 days; slow phase half-life: 9.7 days) leading to a median 1.4-fold increase in glucocerebrosidase intra-monocyte activity from the pre-treatment activity (p = 0.04). In patients receiving long-term treatment, for whom the imiglucerase dose per infusion was chosen on the basis of disease aggressiveness/response, imiglucerase clearance correlated with the administered dose. However, the residual glucocerebrosidase intra-monocyte activity value was dose independent, suggesting that the maintenance of imiglucerase residual activity is patient specific. Endogenous pre-treatment glucocerebrosidase intra-monocyte activity was the most informative single parameter for distinguishing patients without (n = 10) and with a clinical indication (n = 17) for starting enzyme replacement therapy (area under the receiver operating characteristic curve: 0.912; 95% confidence interval 0.8-1; p < 0.001), as confirmed also by a factorial analysis of mixed data., Conclusion: This study provides novel pharmacokinetic data that support current imiglucerase administration regimens and suggests the existence of a glucocerebrosidase activity threshold related to Gaucher disease type 1 aggressiveness. These findings can potentially improve Gaucher disease type 1 management algorithms and clinical decision making.

Introduction: The morbi-mortality related to infective endocarditis (IE) remains high as the epidemiology has changed over the last years: ageing of patients, comorbidity and healthcare-associated infections. To optimize IE management, a weekly endocarditis multidisciplinary meeting (EMM) was set up at our facility. We present the activity report of the EMM., Patients and Methods: All patients hospitalized for IE who were presented at the weekly EMM between January 2013 and June 2017 were prospectively included. The main objective was to assess the impact of the EMM on the management of community-acquired IE and healthcare-associated IE by analyzing in-hospital case fatality., Results: Of the 1139 cases reported during the EMM for suspicion of IE, 493 (86% were definite cases) were selected for the study: 262 patients had community-acquired IE and 231 had healthcare-associated IE; 43% of IEs involved a valvular prosthesis. Following the EMM, infections were documented in 92% of cases: staphylococci in 45% of healthcare-associated IEs and streptococci in 44% of community-acquired IE cases. A septic embolism was diagnosed in 57% of cases. Finally, 49% of patients underwent surgery. The in-hospital case fatality was 12% with no significant difference between community-acquired IEs and healthcare-associated IEs. Case fatality was also significantly higher in elderly patients, in the absence of surgical treatment, initial heart failure, or Staphylococcus aureus IE., Conclusion: The weekly EMM allows our facility to follow the European Society of Cardiology guidelines and to adapt the management of each patient to improve IE prognosis., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: The usage of left-ventricular-assist device (LVAD) is increasing in patients presenting with advanced heart failure. However, device-related infections are a challenge to recognize and to treat, with an important morbidity and mortality rate. The role of nuclear medicine imaging remains not well established for LVAD infections. The present study compared the accuracy of positron emission tomography/computed tomography with 18 F-fludeoxyglucose ( 18 F-FDG PET/CT) and radiolabeled leucocyte scintigraphy for the diagnosis of infections in patients supported with a continuous-flow LVAD., Methods: From a prospectively maintained database, we retrospectively analyzed the diagnostic performance of radiolabeled leucocyte scintigraphy and 18 F-FDG PET/CT in 24 patients who had a LVAD with a suspected device-related infection. Both examinations were routinely performed in all patients. Infection was assessed by the International Society for Heart and Lung Transplantation criteria., Results: Twenty-four patients were included: 15 had a specific VAD infection (5 cardiac-LVAD and 10 driveline), 6 had a VAD-related infection, while 3 patients had a non-VAD-related infection. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.2%, 66.7%, 95.2%, 66.7%, and 91.6%, respectively, for 18 F-FDG-PET; and 71.4%, 100%, 100%, 33.3%, and 75%, respectively, for leucocyte scintigraphy. 18 F-FDG PET/CT showed significantly higher sensitivity (P = 0.01) than leucocyte scintigraphy., Conclusion: 18 F-FDG PET/CT and radiolabeled leucocyte scintigraphy single-photon emission computed tomography carry high performance in the diagnostic of LVAD infections. 18 F-FDG PET/CT shows significantly higher sensitivity and could be proposed as first-line nuclear medicine procedure.

Objective: Pneumocystis pneumonia (PCP) is now predominantly observed in immunosuppressed non-HIV-infected patients. The sensitivity of the PCR is here higher than direct examination (DE) of respiratory secretions because the infection is caused by a lower inoculum of Pneumocystis jirovecii (P. jirovecii). The objective of our retrospective study was to assess the contribution of quantitative PCR (qPCR) in the diagnosis of PCP., Patients and Methods: All patients hospitalized for PCP suspicion with a positive qPCR were included. Irrespective of the qPCR value, patients were initially classified into two groups (infection and colonization [PCP ruled out]) based on clinical, radiological, and microbiological data. Both groups were then compared based on the qPCR value., Results: Between 2013 and 2016, 150 patients were included; 75% of them were not infected with HIV. The diagnosis of PCP was retained for 129 patients and rejected for 21 patients. The DE was negative in 60% of PCP cases. The median value of qPCR was 76,650copies/mL among infected patients and 3220copies/mL among colonized patients. The threshold corresponding to a specificity of 100% was 56,000copies/mL. The optimal value to distinguish an infection from a colonization was 10,100copies/mL., Conclusion: Our study confirms the diagnostic value of the qPCR in immunosuppressed patients, especially when the DE is negative. When the qPCR is˂56,000copies/mL, the result should be interpreted based on the clinical context and paraclinical examinations., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: To confirm the advantage of in situ reconstruction (ISR) over extra-anatomic reconstruction (EAR) for aortic graft infection and determine the most appropriate conduit including autogenous veins, cryopreserved allografts, and synthetic prosthesis (standard, rifampicin of silver polyesters)., Methods: A meta-analysis was conducted with rate of mortality, graft occlusion, amputation, and reinfection. A meta-regression was performed with 4 factors: patients' age, presence of prosthetic-duodenal fistula (PDF), virulent organisms, or nonvirulent organisms., Results: In situ reconstruction over EAR seems to favor all events. For the 5 conduits used for ISR, according to operative mortality, age of the patients looks to have a positive correlation only for silver polyester and no conduit present any advantage in the presence of PDF. Reinfection seems to be not significantly different for the 5 conduits, and only autogenous veins appear to have a positive correlation with infecting organisms., Conclusion: In situ reconstruction may be considered as first-line treatment. Our results suggest that silver polyesters appear to be most appropriate for older patients, and in order to limit reinfection, autogenous veins are probably the most suitable conduit.

Objectives: Guidelines for preventing Pneumocystis pneumonia (PCP) in HIV patients are based on CD4 below 200/mm3. Such cut-off value is suggested to guide prophylaxis in non-HIV conditions (NHIV) especially in autoimmune and inflammatory diseases (AD). We aimed to determine if CD4 could be used to guide PCP prophylaxis in AD., Methods: CD4 and lymphocyte-count were retrospectively studied in patients diagnosed with PCP between January 2013 and February 2016., Results: 129 patients were included. The median CD4-count was 302/mm3 in AD, which was significantly higher than in HIV patients (19/mm3; p<0.0001). Fifty percent (n=10) of AD patients had CD4 counts greater than 300/mm3., Conclusions: Prophylaxis for PCP cannot rely solely on CD4-count in NHIV patients especially in AD.

Objectives: Type 1 Gaucher disease may be related to the presence of autoantibodies. Their clinical significance is questioned. Primary endpoint was to compare the prevalence of autoantibodies in type 1 Gaucher disease patients with healthy subjects, seeking correlations with autoimmune characteristics. Secondary endpoints were to determine whether patients with autoantibodies reported autoimmunity-related symptoms and if genotype, splenectomy or treatment influenced autoantibodies presence., Methods: Type 1 Gaucher disease patients and healthy volunteers were included in this national multicenter exploratory study. Autoantibodies presence was compared in both groups and assessed regarding to genotype, splenectomy, Gaucher disease treatment and autoimmunity-related symptoms., Results: Twenty healthy subjects and 40 type 1 Gaucher disease patients were included. Of the studied group: 15 patients undergone splenectomy, 37 were treated either with enzyme replacement therapy (34) or with substrate reduction therapy (3), 25 were homozygous/heterozygous for the N370S mutation. In type 1 Gaucher disease group (studied group), 52% had positive autoantibodies versus 26% in control group. Antiphospholipid antibodies were more frequent in the studied group (30% vs. 5%), but without correlation to thrombosis, osteonecrosis or bone infarcts. In the studied group, antinuclear antibodies were more frequent (25% vs. 16%). None of the patients with autoantibodies had clinical manifestations of autoimmune diseases. Autoantibodies were not correlated with treatment, genotype, or splenectomy, except for anticardiolipid, more frequent in splenectomized patients., Conclusions: In type 1 Gaucher disease, autoantibodies were more frequent compared to a healthy population. However, they were not associated with an increased prevalence of clinical active autoimmune diseases., (Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Introduction: The Bentall procedure is a cardiac surgery involving graft replacement of the aortic valve, aortic root and ascending aorta. Graft infection after Bentall's procedure (BGI) is infrequent but severe, and often difficult to diagnose and treat., Patients and Methods: A retrospective cohort study was performed using the Bordeaux endocarditis database of adult patients admitted to the Bordeaux University Medical Hospital for BGI between 2008 and 2014. Published case reports were identified in the literature., Results: We identified 10 BGI patients in the database and 13 in the literature. The majority of infections were late-onset (20/23) and occurred as a result of gram positive cocci bacterial infection (16/22). Detailed diagnoses of the described BGI were determined using echocardiography, computed tomography (CT) and positron emission tomography/CT (PET/CT). Labeled-leukocyte scintigraphy was not reported in any case. Prolonged antibiotic therapy and surgery were found to be the treatment of choice for BGI; however it was not always possible to perform a surgical intervention. Clinical relapses occurred even with a negative PET/CT, while PET/CT consistently positive for BGI occurred in the absence of clinical relapse. This suggests that the use of PET/CT for follow-up is questionable., Conclusion: Diagnosis of BGI is difficult, due to the combination of clinical, biological, and radiological observations obtained through transesophageal echocardiography and CT. PET/CT is an alternative method to diagnosis BGI, but its impact on clinical management remains unclear. Current data suggests that if surgical replacement of the prosthesis is not possible, patients should be treated with prolonged antibiotic therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the majority of patients (90% in Europe and USA, but less in other regions), is characterized by effects on the viscera, whereas types 2 and 3 are also associated with neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in the GBA1 gene should be identified as they may be of prognostic value in some cases. Patients with type-1 GD-but also carriers of GBA1 mutation-have been found to be predisposed to developing Parkinson's disease, and the risk of neoplasia associated with the disease is still subject to discussion. Disease-specific treatment consists of intravenous enzyme replacement therapy (ERT) using one of the currently available molecules (imiglucerase, velaglucerase, or taliglucerase). Orally administered inhibitors of glucosylceramide biosynthesis can also be used (miglustat or eliglustat).

Introduction: Hyperammonemia attributed to multiple myeloma has been rarely reported., Case Report: We report a 63-year-old man who was admitted to an intensive care unit for confusion and altered mental status progressing to coma that was related to a relapsing multiple myeloma. Chemotherapy allowed the reduction of serum ammonia and the return to a normal state of consciousness., Conclusion: Hyperammonemic encephalopathy is a rare complication of multiple myeloma and is associated with high in-patient mortality. To our knowledge, this is the first case of hyperammonemic encephalopathy due to a relapsing myeloma diagnosed and treated in intensive care unit., (Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)