Publications by authors named "Yves Hansmann"

79 Publications

Follow-up of COVID-19 patients: LA is transient but other aPLs are persistent.

Autoimmun Rev 2021 Apr 16:102822. Epub 2021 Apr 16.

Service d'Immunologie Clinique-Médecine Interne, Centre National de Référence des Maladies Auto-immunes et Systémiques Rares Est/Sud-Ouest RESO, Hôpitaux Universitaires de Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2021.102822DOI Listing
April 2021

Sex differences in the evolution of neutralizing antibodies to SARS-CoV-2.

J Infect Dis 2021 Mar 7. Epub 2021 Mar 7.

CHU de Strasbourg, Laboratoire de virologie, F-67091 Strasbourg, France.

We measured Anti-Spike (S), Nucleoprotein (N) and neutralizing antibodies (NAbs) in sera from 308 RT-qPCR + healthcare workers with mild disease, collected at two time-points up to 6 months after symptom onset. At Month 1 (M1), anti-S and N antibody levels were higher in males > 50 years or with a body mass index (BMI) > 25. At M3-6, anti-S and anti-N antibodies were detected in 99% and 59% of individuals, respectively. Anti-S antibodies and NAbs declined faster in males than in females, independently of age and BMI, suggesting an association of sex with evolution of the humoral response.
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http://dx.doi.org/10.1093/infdis/jiab127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989436PMC
March 2021

Factors associated with coinfections in invasive aspergillosis: a retrospective cohort study.

Clin Microbiol Infect 2021 Mar 2. Epub 2021 Mar 2.

Department of Haematology, Institut de Cancérologie de Strasbourg (ICANS), Strasbourg, France; Université de Strasbourg, Inserm UMR-S1113/IRFAC, Strasbourg, France. Electronic address:

Objectives: To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality.

Patients And Methods: We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis.

Results: Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8-43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2-4.4)), other haematological malignancies (OR 2.1 (1.2-3.8)), other underlying diseases (OR 4.3 (1.4-13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2-3.0)), fever (OR 2.4 (1.5-4.1)), tracheal intubation (OR 2.6 (1.5-4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1-6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3-3.7) and OR 2.2 (1.2-4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1-1.9), p < 0.01).

Conclusions: Coinfections are frequent in IA patients and are associated with higher mortality.
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http://dx.doi.org/10.1016/j.cmi.2021.02.021DOI Listing
March 2021

Revised version (INFD-D-20-00242): impact of 16S rDNA sequencing on clinical treatment decisions: a single center retrospective study.

BMC Infect Dis 2021 Feb 18;21(1):190. Epub 2021 Feb 18.

Maladies Infectieuses et Tropicales, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: PCRs targeting 16S ribosomal DNA (16S PCR) followed by Sanger's sequencing can identify bacteria from normally sterile sites and complement standard analyzes, but they are expensive. We conducted a retrospective study in the Strasbourg University Hospital to assess the clinical impact of 16S PCR sequencing on patients' treatments according to different sample types.

Methods: From 2014 to 2018, 806 16S PCR samples were processed, and 191 of those were positive.

Results: Overall, the test impacted the treatment of 62 of the 191 patients (32%). The antibiotic treatment was rationalized in 31 patients (50%) and extended in 24 patients (39%), and an invasive procedure was chosen for 7 patients (11%) due to the 16S PCR sequencing results. Positive 16S PCR sequencing results on cerebrospinal fluid (CSF) had a greater impact on patients' management than positive ones on cardiac valves (p = 0.044). The clinical impact of positive 16S PCR sequencing results were significantly higher when blood cultures were negative (p < 0.001), and this difference appeared larger when both blood and sample cultures were negative (p < 0.001). The diagnostic contribution of 16S PCR was higher in patients with previous antibiotic treatment (p < 0.001).

Conclusion: In all, 16S PCR analysis has a significant clinical impact on patient management, particularly for suspected CSF infections, for patients with culture-negative samples and for those with previous antibiotic treatments.
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http://dx.doi.org/10.1186/s12879-021-05892-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890971PMC
February 2021

SARS-CoV-2 viral load in nasopharyngeal swabs in the emergency department does not predict COVID-19 severity and mortality.

Acad Emerg Med 2021 03 5;28(3):306-313. Epub 2021 Feb 5.

INSERM (French National Institute of Health and Medical Research, UMR 1260, Regenerative NanoMedicine (RNM), Fédération de Médecine Translationnelle (FMTS), University of Strasbourg, Strasbourg, France.

Introduction: The ongoing COVID-19 pandemic has led to devastating repercussions on health care systems worldwide. This viral infection has a broad clinical spectrum (ranging from influenza-like disease, viral pneumonia, and hypoxemia to acute respiratory distress syndrome requiring prolonged intensive care unit stays). The prognostic impact of measuring viral load on nasopharyngeal swab specimens (by reverse transcriptase polymerase chain reaction [RT-PCR]) is yet to be elucidated.

Methods: Between March 3 and April 5, 2020, we conducted a retrospective study on a cohort of COVID-19 patients (mild or severe disease) who were hospitalized after presenting to the emergency department (ED) and had at least one positive nasopharyngeal swab during their hospital stay. We led our study at the University Hospitals of Strasbourg in the Greater East region of France, one of the pandemic's epicenters in Europe.

Results: We have collected samples from a cohort of 287 patients with a confirmed diagnosis of COVID-19 who were included in our study. Nearly half of them (50.5%) presented a mild form of the disease, while the other half (49.5%) presented a severe form, requiring mechanical ventilation. Median (interquartile range) viral load on the initial upper respiratory swab at admission was 4.76 (3.29-6.06) log copies/reaction. When comparing survivors and nonsurvivors, this viral load measurement did not differ according to subgroups (p = 0.332). Additionally, we have found that respiratory viral load measurement was predictive of neither in-hospital mortality (adjusted odds ratio [AOR] = 1.05, 95% confidence interval [CI] = 0.85 to 1.31, p = 0.637) nor disease severity (AOR = 0.88, 95% CI = 0.73 to 1.06, p = 0.167).

Conclusion: Respiratory viral load measurement on the first nasopharyngeal swab (by RT-PCR) during initial ED management is neither a predictor of severity nor a predictor of mortality in SARS-CoV-2 infection. Host response to this viral infection along with the extent of preexisting comorbidities might be more foretelling of disease severity than the virus itself.
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http://dx.doi.org/10.1111/acem.14217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014851PMC
March 2021

D-Dimers Level as a Possible Marker of Extravascular Fibrinolysis in COVID-19 Patients.

J Clin Med 2020 Dec 24;10(1). Epub 2020 Dec 24.

Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, 67000 Strasbourg, France.

Background And Objective: Host defence mechanisms to counter virus infection include the activation of the broncho-alveolar haemostasis. Fibrin degradation products secondary to extravascular fibrin breakdown could contribute to the marked increase in D-Dimers during COVID-19. We sought to examine the prognostic value on lung injury of D-Dimers in non-critically ill COVID-19 patients without thrombotic events.

Methods: This study retrospectively analysed hospitalized COVID-19 patients classified according to a D-Dimers threshold following the COVID-19 associated haemostatic abnormalities (CAHA) classification at baseline and at peak (Stage 1: D-Dimers less than three-fold above normal; Stage 2: D-Dimers three- to six-fold above normal; Stage 3: D-Dimers six-fold above normal). The primary endpoint was the occurrence of critical lung injuries on chest computed tomography. The secondary outcome was the composite of in-hospital death or transfer to the intensive care unit (ICU).

Results: Among the 123 patients included, critical lung injuries were evidenced in 8 (11.9%) patients in Stage 1, 6 (20%) in Stage 2 and 15 (57.7%) in Stage 3 ( = 0.001). D-Dimers staging at peak was an independent predictor of critical lung injuries regardless of the inflammatory burden assessed by CRP levels (OR 2.70, 95% CI (1.50-4.86); < 0.001) and was significantly associated with increased in-hospital death or ICU transfer (14.9 % in Stage 1, 50.0% in Stage 2 and 57.7% in Stage 3 ( < 0.001)). D-Dimers staging at peak was an independent predictor of in-hospital death or ICU transfer (OR 2.50, CI 95% (1.27-4.93); = 0.008).

Conclusions: In the absence of overt thrombotic events, D-Dimers quantification is a relevant marker of critical lung injuries and dismal patient outcome.
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http://dx.doi.org/10.3390/jcm10010039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795726PMC
December 2020

Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors.

Viruses 2020 12 2;12(12). Epub 2020 Dec 2.

Virology Laboratory, Strasbourg University Hospitals, 67000 Strasbourg, France.

JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate. In this work, we investigated the compartmentalization of JCV strains as well as the humoral neutralizing response in various matrices to further understand the pathophysiology of PML and define markers of survival. Four patients were included, of which three died in the few months following PML onset. Cerebrospinal fluid (CSF) viral loads were the highest, with plasma samples having lower viral loads and urine samples being mostly negative. Whether at PML onset or during follow-up, neutralizing antibody (NAb) titers directed against the same autologous strain (genotype or mutant) were the highest in plasma, with CSF titers being on average 430-fold lower and urine titers 500-fold lower at the same timepoint. Plasma NAb titers against autologous genotype or mutant were lower in non-survivor patients, though no neutralization "blind spot" was observed. The surviving patient was followed up until nine months after PML onset and presented, at that time, an increase in neutralizing titers, from 38-fold against the autologous genotype to around 200-fold against PML mutants. Our results suggest that patients' humoral neutralizing response against their autologous strain may play a role in PML outcome, with survivors developing high NAb titers in both plasma and CSF.
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http://dx.doi.org/10.3390/v12121380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761562PMC
December 2020

The BASIC Score: A Useful Tool to Identify Patients at High Risk of Early Progression to Severe Coronavirus Disease 2019.

Open Forum Infect Dis 2020 Oct 1;7(10):ofaa405. Epub 2020 Sep 1.

CHU de Strasbourg, Department of Infectious and Tropical Diseases, Strasbourg, France.

We developed a score, with easily accessible data (age, sex, body mass index, dyspnea, inflammatory parameters), to predict the risk of rapid progression to severe coronavirus disease 2019. Using a cutoff of >6 points, the negative predictive value was 87%.
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http://dx.doi.org/10.1093/ofid/ofaa405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499730PMC
October 2020

Clinical characteristics and risk factors associated with severe COVID-19: prospective analysis of 1,045 hospitalised cases in North-Eastern France, March 2020.

Euro Surveill 2020 12;25(48)

CHU de Strasbourg, Department of Infectious and Tropical Diseases; Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.

BackgroundIn March 2020, the COVID-19 outbreak was declared a pandemic by the World Health Organization.AimOur objective was to identify risk factors predictive of severe disease and death in France.MethodsIn this prospective cohort study, we included patients ≥ 18 years old with confirmed COVID-19, hospitalised in Strasbourg and Mulhouse hospitals (France), in March 2020. We respectively compared patients who developed severe disease (admission to an intensive care unit (ICU) or death) and patients who died, to those who did not, by day 7 after hospitalisation.ResultsAmong 1,045 patients, 424 (41%) had severe disease, including 335 (32%) who were admitted to ICU, and 115 (11%) who died. Mean age was 66 years (range: 20-100), and 612 (59%) were men. Almost 75% of patients with body mass index (BMI) data (n = 897) had a BMI ≥ 25 kg/m2 (n = 661). Independent risk factors associated with severe disease were advanced age (odds ratio (OR): 1.1 per 10-year increase; 95% CrI (credible interval): 1.0-1.2), male sex (OR: 2.1; 95% CrI: 1.5-2.8), BMI of 25-29.9 kg/m2 (OR: 1.8; 95% CrI: 1.2-2.7) or ≥ 30 (OR: 2.2; 95% CrI: 1.5-3.3), dyspnoea (OR: 2.5; 95% CrI: 1.8-3.4) and inflammatory parameters (elevated C-reactive protein and neutrophil count, low lymphocyte count). Risk factors associated with death were advanced age (OR: 2.7 per 10-year increase; 95% CrI: 2.1-3.4), male sex (OR: 1.7; 95% CrI: 1.1-2.7), immunosuppression (OR: 3.8; 95% CrI: 1.6-7.7), diabetes (OR: 1.7; 95% CrI: 1.0-2.7), chronic kidney disease (OR: 2.3; 95% CrI: 1.3-3.9), dyspnoea (OR: 2.1; 95% CrI: 1.2-3.4) and inflammatory parameters.ConclusionsOverweightedness, obesity, advanced age, male sex, comorbidities, dyspnoea and inflammation are risk factors for severe COVID-19 or death in hospitalised patients. Identifying these features among patients in routine clinical practice might improve COVID-19 management.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.48.2000895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716399PMC
December 2020

Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients.

J Infect Dis 2021 02;223(4):600-609

Service d'Imagerie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings.

Methods: The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed.

Results: Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%).

Conclusions: Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.
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http://dx.doi.org/10.1093/infdis/jiaa745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798956PMC
February 2021

Disappearance of TBEV Circulation among Rodents in a Natural Focus in Alsace, Eastern France.

Pathogens 2020 Nov 10;9(11). Epub 2020 Nov 10.

Nancy Laboratory for Rabies and Wildlife, The French Agency for Food, Environmental and Occupational Health & Safety (ANSES), CS 40009, 54220 Malzéville, France.

Tick-borne encephalitis virus (TBEV) depends mainly on a fragile mode of transmission, the co-feeding between infected nymphs and larvae on rodents, and thus persists under a limited set of biotic and abiotic conditions. If these conditions change, natural TBEV foci might be unstable over time. We conducted a longitudinal study over seven years in a mountain forest in Alsace, Eastern France, located at the western border of known TBEV distribution. The objectives were (i) to monitor the persistence of TBEV circulation between small mammals and ticks and (ii) to discuss the presence of TBEV circulation in relation to the synchronous activity of larvae and nymphs, to the densities of questing nymphs and small mammals, and to potential changes in meteorological conditions and deer densities. Small mammals were trapped five times per year from 2012 to 2018 to collect blood samples and record the presence of feeding ticks, and were then released. Questing nymphs were collected twice a year. Overall, 1344 different small mammals ( and ) were captured and 2031 serum samples were tested for the presence of antibodies against TBEV using an in-house ELISA. Seropositive rodents (2.1%) were only found from 2012 to 2015, suggesting that the virus disappeared afterwards. In parallel, we observed unusual variations in inter-annual nymph abundance and intra-annual larval activity that could be related to exceptional meteorological conditions. Changes in the densities of questing nymphs and deer associated with the natural stochastic variations in the frequency of contacts between rodents and infected ticks may have contributed to the endemic fadeout of TBEV on the study site. Further studies are needed to assess whether such events occur relatively frequently in the area, which could explain the low human incidence of TBE in Alsace and even in other areas of France.
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http://dx.doi.org/10.3390/pathogens9110930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697581PMC
November 2020

The diagnostic utility of the "Thwaites' system" and "lancet consensus scoring system" in tuberculous vs. non-tuberculous subacute and chronic meningitis: multicenter analysis of 395 adult patients.

BMC Infect Dis 2020 Oct 23;20(1):788. Epub 2020 Oct 23.

Department of Internal Medicine, Section of Infectious Diseases, UT Health McGovern Medical School, University of Texas Health Sciences Center, 6431 Fannin St. 2.112 MSB, Houston, Texas, 77030m, USA.

Background: Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The "Thwaites' system" and "Lancet consensus scoring system" are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown.

Methods: A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The "Thwaites' system" and "Lancet consensus scoring system" scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The "Thwaites' system" and "Lancet consensus scoring system" suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively.

Results: A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P < 0.001). A total of 162 patients with TBM and 233 patients with non-TBM had unknown (140, 60.1%), fungal (41, 17.6%), viral (29, 12.4%), miscellaneous (16, 6.7%), and bacterial (7, 3.0%) etiologies. TMB patients were older and presented with lower Glasgow coma scores, lower CSF glucose and higher CSF protein (P < 0.001). Both criteria were able to distinguish TBM from bacterial meningitis; only the Lancet score was able to differentiate TBM from fungal, viral, and unknown etiologies even though significant overlap occurred between the etiologies (P < .001). Both criteria showed poor diagnostic accuracy to distinguish TBM from non-TBM etiologies (AUC-ROC was <. 5), but Lancet consensus scoring system was fair in diagnosing TBM (AUC-ROC was .738), sensitivity of 50%, and specificity of 89.3%.

Conclusion: Both criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.
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http://dx.doi.org/10.1186/s12879-020-05502-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585215PMC
October 2020

Progressive multifocal leukoencephalopathy and sarcoidosis under interleukin 7: The price of healing.

Neurol Neuroimmunol Neuroinflamm 2020 09 11;7(5). Epub 2020 Aug 11.

From the Department of Clinical Immunology and Internal Medicine (A.G., V.G, Y.D., V.P., T.M., A.-S.K.), National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiency, Strasbourg University Hospital; Université de Strasbourg (A.G., M.S., V.G., Y.D., T.M., A.-S.K.), INSERM UMR - S1109; Université de Strasbourg (A.G., M.S., Y.D., C.L., Y.H., T.M., A.-S.K.), Faculty of Medicine; Virology Laboratory (M.S.), Strasbourg University Hospital; Université de Strasbourg (V.G.), Faculty of Pharmacy, Illkirch, France; Internal Medicine and Intensive Care (C.K.), Strasbourg University Hospital; Department of Dermatology (C.L.), Strasbourg University Hospital; Department of Neurology (L.K.), INSERM U1119, Biopathologie de La Myéline, Neuroprotection et Stratégies Thérapeutiques, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS); Université de Strasbourg (A.M., R.C.), INSERM UMR-S1109, GENOMAX Platform, Fédération Hospitalo-Universitaire OMICARE, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), LabEx TRANSPLANTEX; Department of Infectious Diseases (Y.H.), Strasbourg University Hospital; and Departement of Pneumology (S.H.), Strasbourg University Hospital, Strasbourg, France.

Objective: To report the association of JC virus infection of the brain (progressive multifocal encephalopathy [PML]) during the course of sarcoidosis and the challenging balance between immune reconstitution under targeted cytokine interleukin 7 (IL7) therapy for PML and immunosuppression for sarcoidosis.

Methods: Original case report including deep sequencing (whole-exome sequencing) to exclude a primary immunodeficiency (PID) and review of the literature of cases of PML and sarcoidosis.

Results: We report and discuss here a challenging case of immune reconstitution with IL7 therapy for PML in sarcoidosis in a patient without evidence for underling PID or previous immunosuppressive therapy.

Conclusions: New targeted therapies in immunology and infectiology open the doors of more specific and more specialized therapies for patients with immunodeficiencies, autoimmune diseases, or cancers. However, before instauration of these treatments, the risk of immune reconstitution inflammatory syndrome and potential exacerbation of an underlying disease must be considered. It is particularly true in case of autoimmune disease such as sarcoidosis or lupus.
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http://dx.doi.org/10.1212/NXI.0000000000000862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428361PMC
September 2020

CT lung lesions as predictors of early death or ICU admission in COVID-19 patients.

Clin Microbiol Infect 2020 Oct 24;26(10):1417.e5-1417.e8. Epub 2020 Jul 24.

Department of Infectious Disease, Strasbourg University Hospital, Strasbourg, France.

Objective: The main objective of this study was to investigate the prognostic value of early systematic chest computed tomography (CT) with quantification of lung lesions in coronavirus disease 2019 (COVID-19) patients.

Methods: We studied 572 patients diagnosed with COVID-19 (confirmed using polymerase chain reaction) for whom a chest CT was performed at hospital admission. Visual quantification was used to classify patients as per the percentage of lung parenchyma affected by COVID-19 lesions: normal CT, 0-10%, 11-25%, 26-50%, 51-75% and >75%. The primary endpoint was severe disease, defined by death or admission to the intensive care unit in the 7 days following first admission.

Results: The mean patient age was 66.0 ± 16.0 years, and 343/572 (60.0%) were men. The primary endpoint occurred in 206/572 patients (36.0%). The extent of lesions on initial CT was independently associated with prognosis (odds ratio = 2.35, 95% confidence interval 1.24-4.46; p < 0.01). Most patients with lung involvement >50% (66/95, 69.5%) developed severe disease compared to patients with lung involvement of 26-50% (70/171, 40.9%) and ≤25% (70/306, 22.9%) (p < 0.01 and p < 0.01, respectively). None of the patients with normal CT (0/14) had severe disease.

Conclusion: Chest CT findings at admission are associated with outcome in COVID-19 patients.
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http://dx.doi.org/10.1016/j.cmi.2020.07.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378475PMC
October 2020

Rapid Radiological Worsening and Cytokine Storm Syndrome in COVID-19 Pneumonia.

Eur J Case Rep Intern Med 2020 2;7(7):001822. Epub 2020 Jul 2.

Department of Infectious Diseases, Strasbourg University Hospital, Strasbourg, France.

Background: In June 2020, a large randomised controlled clinical trial in the UK found that dexamethasone was effective in reducing the number of deaths in patients with severe coronavirus disease 2019 (COVID-19).

Case Description: We describe a patient with rapid worsening of COVID-19 pneumonia and its dramatic improvement under corticosteroids.

Discussion: Corticosteroids could be useful in patients with an inflammatory profile, considering that acute respiratory distress syndrome may be the consequence of cytokine storm syndrome.

Learning Points: One of the main pathophysiological hypotheses for severe COVID-19 pneumonia is inappropriate immunological hyperactivation.Corticosteroid therapy may be useful in these patients.
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http://dx.doi.org/10.12890/2020_001822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350974PMC
July 2020

Tick-Borne Encephalitis Virus: Seasonal and Annual Variation of Epidemiological Parameters Related to Nymph-to-Larva Transmission and Exposure of Small Mammals.

Pathogens 2020 Jun 27;9(7). Epub 2020 Jun 27.

Nancy Laboratory for Rabies and Wildlife, The French Agency for Food, Environmental and Occupational Health and Safety (ANSES), 54220 Malzéville, France.

A greater knowledge of the ecology of the natural foci of tick-borne encephalitis virus (TBEV) is essential to better assess the temporal variations of the risk of tick-borne encephalitis for humans. To describe the seasonal and inter-annual variations of the TBEV-cycle and the epidemiological parameters related to TBEV nymph-to-larva transmission, exposure of small mammals to TBEV, and tick aggregation on small mammals, a longitudinal survey in ticks and small mammals was conducted over a 3-year period in a mountain forest in Alsace, eastern France. TBEV prevalence in questing nymphs was lower in 2013 than in 2012 and 2014, probably because small mammals ( and ) were more abundant in 2012, which reduced tick aggregation and co-feeding transmission between ticks. The prevalence of TBEV in questing nymphs was higher in autumn than spring. Despite these variations in prevalence, the density of infected questing nymphs was constant over time, leading to a constant risk for humans. The seroprevalence of small mammals was also constant over time, although the proportion of rodents infested with ticks varied between years and seasons. Our results draw attention to the importance of considering the complex relationship between small mammal densities, tick aggregation on small mammals, density of infected questing nymphs, and prevalence of infected nymphs in order to forecast the risk of TBEV for humans.
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http://dx.doi.org/10.3390/pathogens9070518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400523PMC
June 2020

Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birth.

Am J Obstet Gynecol 2020 12 15;223(6):914.e1-914.e15. Epub 2020 Jun 15.

Department of Obstetrics and Gynecology, Strasbourg University Hospitals, Strasbourg, France.

Background: Despite the mainly reassuring outcomes for pregnant women with coronavirus disease 2019 reported by previous case series with small sample sizes, some recent reports of severe maternal morbidity requiring intubation and of maternal deaths show the need for additional data about the impact of coronavirus disease 2019 on pregnancy outcomes.

Objective: This study aimed to report the maternal characteristics and clinical outcomes of pregnant women with coronavirus disease 2019.

Study Design: This retrospective, single-center study includes all consecutive pregnant women with confirmed (laboratory-confirmed) or suspected (according to the Chinese management guideline [version 7.0]) coronavirus disease 2019, regardless of gestational age at diagnosis, admitted to the Strasbourg University Hospital (France) from March 1, 2020, to April 3, 2020. Maternal characteristics, laboratory and imaging findings, and maternal and neonatal outcomes were extracted from medical records.

Results: The study includes 54 pregnant women with confirmed (n=38) and suspected (n=16) coronavirus disease 2019. Of these, 32 had an ongoing pregnancy, 1 had a miscarriage, and 21 had live births: 12 vaginal and 9 cesarean deliveries. Among the women who gave birth, preterm deliveries were medically indicated for their coronavirus disease 2019-related condition for 5 of 21 women (23.8%): 3 (14.3%) before 32 weeks' gestation and 2 (9.5%) before 28 weeks' gestation. Oxygen support was required for 13 of 54 women (24.1%), including high-flow oxygen (n=2), noninvasive (n=1) and invasive (n=3) mechanical ventilation, and extracorporeal membrane oxygenation (n=1). Of these, 3, aged 35 years or older with positive test result for severe acute respiratory syndrome coronavirus 2 using reverse transcription polymerase chain reaction, had respiratory failure requiring indicated delivery before 29 weeks' gestation. All 3 women were overweight or obese, and 2 had an additional comorbidity.

Conclusion: Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birth. Its association with other well-known risk factors for severe maternal morbidity in pregnant women with no infection, including maternal age above 35 years, overweight, and obesity, suggests further studies are required to determine whether these risk factors are also associated with poorer maternal outcome in these women.
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http://dx.doi.org/10.1016/j.ajog.2020.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294260PMC
December 2020

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.

Radiology 2020 11 16;297(2):E242-E251. Epub 2020 Jun 16.

From the Hôpitaux Universitaires de Strasbourg, Service d'Imagerie 2, Hôpital de Hautepierre, Strasbourg, France (S.K.).

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were () positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, () severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, () neurologic manifestations, and () abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student test or Wilcoxon test. < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.
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http://dx.doi.org/10.1148/radiol.2020202222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301613PMC
November 2020

The Good, the Bad, and the Hoax: When Publication Instantaneously Impacts Treatment Strategies for COVID-19.

Antimicrob Agents Chemother 2020 07 22;64(8). Epub 2020 Jul 22.

CHU de Strasbourg, Service de Maladies Infectieuses et Tropicales, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.

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http://dx.doi.org/10.1128/AAC.01127-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526849PMC
July 2020

Assessment of Borrelia miyamotoi in febrile patients and ticks in Alsace, an endemic area for Lyme borreliosis in France.

Parasit Vectors 2020 Apr 17;13(1):199. Epub 2020 Apr 17.

University of Strasbourg, Virulence bactérienne précoce UR7290-Lyme borreliosis group, FMTS - CHRU Strasbourg, Institut de Bactériologie, Strasbourg, France.

Background: Borrelia miyamotoi is a relapsing fever Borrelia species transmitted by ticks of the Ixodes ricinus complex. Human disease caused by B. miyamotoi was first described in Russia and later in the USA and Japan. Additionally, five cases of meningoencephalitis in immunocompromised patients and one case in an apparently immunocompetent patient were described.

Methods: We investigated the presence of B. miyamotoi in I. ricinus nymphs and in patients suspected of human granulocytic anaplasmosis, in Alsace (France), an endemic area for I. ricinus ticks and Lyme borreliosis, using direct (PCR) and indirect diagnosis (glycerophosphoryldiester-phosphodiesterase (GlpQ) serology).

Results: Borrelia miyamotoi was found in 2.2% of 4354 ticks collected between 2013 and 2016. None of the 575 blood samples, collected from the patients suspected of HGA, was found positive for B. miyamotoi by PCR. Acute and late sera from 138 of these 575 patients were available. These paired sera were tested for IgM and IgG antibodies against the B. miyamotoi GlpQ antigen. A total of 14 out of 138 patients had at least one positive parameter (i.e. anti-GlpQ IgG and/or IgM). One patient seroconverted for IgG, and three had isolated IgM in the acute serum. These three patients were treated with doxycycline which could have prevented seroconversion. After reviewing clinical data and other biological tests performed, co-exposure among different microorganisms vectored by ticks or serological cross-reactivity could not be ruled out in these different cases. One patient had persistent IgG, which strongly suggests previous exposure to B. miyamotoi.

Conclusions: Humans can be exposed to B. miyamotoi through tick bites in Alsace. We present serological data for possible B. miyamotoi exposure or infection of patients with fever after tick bite. Future studies should determine the incidence, clinical course and burden of this emerging tick-borne disease in other parts of Western Europe.
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http://dx.doi.org/10.1186/s13071-020-04071-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165395PMC
April 2020

Impact of Setting up an "Endocarditis Team" on the Management of Infective Endocarditis.

Open Forum Infect Dis 2019 Sep 16;6(9):ofz308. Epub 2019 Jul 16.

Department of Infectious Disease, Strasbourg University Hospital, Strasbourg, France.

Background: Infective endocarditis (IE) remains a severe disease with a high mortality rate. Therefore, guidelines encourage the setup of a multidisciplinary group in reference centers. The present study evaluated the impact of this "Endocarditis Team" (ET).

Methods: We conducted a monocentric observational study at Strasbourg University Hospital, Strasbourg, France, between 2012 and 2017. The primary end point was in-hospital mortality. Secondary end points were 6-month and 1-year mortality, surgery rate, time to surgical procedure, duration of effective antibiotic therapy, length of in-hospital stay, and sequelae. We also assessed predictors of in-hospital mortality.

Results: We analyzed 391 episodes of IE. In the post-ET period, there was a nonsignificant decrease in in-hospital mortality (20.3% vs 14.7%, respectively; = .27) and sequelae, along with a significant reduction in time to surgery (16.4 vs 10.3 days, respectively; = .049), duration of antibiotic therapy (55.2 vs 47.2 days, respectively; < .001), and length of in-hospital stay (40.6 vs 31.9 days, respectively; < .01). In a multivariate analysis, the post-ET period was positively associated with survival (odds ratio, 0.45; 95% confidence interval, 0.20-0.96; = .048).

Conclusions: This multidisciplinary approach exerted a positive impact on the management of IE and should be considered in all hospitals managing IE.
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http://dx.doi.org/10.1093/ofid/ofz308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735925PMC
September 2019

Virulence of beta-hemolytic streptococci in infective endocarditis.

Infection 2020 Feb 13;48(1):91-97. Epub 2019 Sep 13.

Department of Infectious Disease, Strasbourg University Hospital, Strasbourg, France.

Background: Streptococci involved in infective endocarditis (IE) primarily comprise alpha- or non-hemolytic streptococci (ANHS). Moreover, beta-hemolytic streptococci (BHS) can be involved, and guidelines recommend the addition of gentamicin for the first 2 weeks of treatment and the consideration of early surgery in such cases. This study compared the morbidity and mortality associated with IE depending on the microorganisms involved (BHS, ANHS, staphylococci, and enterococci).

Methods: We conducted a retrospective observational study between 2012 and 2017 in a single hospital in France. The endpoints were overall in-hospital mortality, 1-year mortality and the occurrence of complications.

Results: We analyzed 316 episodes of definite IE including 150 (38%), 96 (25%), 46 (12%), and 24 cases (6%) of staphylococcal, ANHS, enterococcal, and BHS IE, respectively. In-hospital mortality was significantly higher in the staphylococcal (n = 40; 26.7%) and BHS groups (n = 6; 25.0%) than in the ANHS (n = 9; 9.4%) and enterococcal groups (n = 5; 10.9%) (all p < 0.01). The rates of septic shock and cerebral emboli were also higher in the BHS group than in the ANHS group [n = 7 (29.2%) vs. n = 3 (3.1%), p < 0.001; n = 7 (29.2%) vs. n = 12 (12.5%); p = 0.05, respectively].

Conclusion: This study confirmed that BHS IE has a more severe prognosis than ANHS IE. The virulence of BHS may be similar to that of staphylococci, justifying increased monitoring of these patients and more 'aggressive' treatments such as early surgery.
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http://dx.doi.org/10.1007/s15010-019-01358-7DOI Listing
February 2020

Safety and efficacy of percutaneous instrumentation combined with antibiotic treatment in spondylodiscitis.

Orthop Traumatol Surg Res 2019 10 27;105(6):1165-1170. Epub 2019 Aug 27.

Service de chirurgie du Rachis, hôpitaux universitaires de Strasbourg, 67200 Strasbourg, France.

Background: Patients with spondylodiscitis are treated with antibiotics and braces for 6 to 12 weeks. Braces aim to decrease pain and prevent kyphotic deformity due to vertebral body collapse. Percutaneous instrumentation could be an alternative to influence pain and patient's autonomy.

Purpose: The purpose of this study was to analyze back pain, quality of life, sagittal deformity, and complications after percutaneous instrumentation in spondylodiscitis.

Patients And Methods: VAS for back pain, EQ-5D, radiographic sagittal index were assessed retrospectively for 28 patients who had a standardized follow-up at 5 days, 6 weeks, 3 months, 1 and 2 years. Probabilities>0.95 indicated significant changes (Bayesian model).

Results: VAS was 7.0 preoperatively, 3.2 (day 5), 2.2 (6 weeks), 1.9 (3 months), 1.6 (1 year), 1.4 (2 years): probabilities>0.95 within 6 weeks. EQ-5D was 0.229 preoperatively, 0.563 (6 weeks), 0.687 (3 months), 0.755 (1 year), 0.787 (2 years): probabilities>0.95 within 1 year. Sagittal index was 15.1° preoperatively, 9.6° postoperatively: probability>0.95. Inter-body fusion was: complete 60.7%, partial 17.9%, and nonunion 21.4%. Antibiotic treatment was stopped at 6 weeks in 82.1%, at 3 months in 17.9%, without septic complication.

Conclusion: Percutaneous instrumentation improved pain control, quality of life and prevented kyphosis. Antibiotic treatment was not influenced. Septic complications were not observed.

Level Of Evidence: IV.
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http://dx.doi.org/10.1016/j.otsr.2019.05.016DOI Listing
October 2019

Tick-borne encephalitis virus: molecular determinants of neuropathogenesis of an emerging pathogen.

Crit Rev Microbiol 2019 Aug 3;45(4):472-493. Epub 2019 Jul 3.

Virology Laboratory, University Hospital of Strasbourg , Strasbourg , France.

tick vector, and a vertebrate reservoir, such as small mammals (rodents, or shrews). Humans are accidentally involved in this transmission cycle. Tick-borne encephalitis (TBE) has been a growing public health problem in Europe and Asia over the past 30 years. The mechanisms involved in the development of TBE are very complex and likely multifactorial, involving both host and viral factors. The purpose of this review is to provide an overview of the current literature on TBE neuropathogenesis in the human host and to demonstrate the emergence of common themes in the molecular pathogenesis of TBE in humans. We discuss and review data on experimental study models and on both viral (molecular genetics of TBEV) and host (immune response, and genetic background) factors involved in TBE neuropathogenesis in the context of human infection.
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http://dx.doi.org/10.1080/1040841X.2019.1629872DOI Listing
August 2019

[Epidemiology of Lyme borreliosis in France - both certainties and uncertainties].

Sante Publique 2019 May;S1(HS):51-63

Epidemiological evidence for tick-borne infections, particularly those related to Lyme borreliosis, is heterogeneous. Lyme borreliosis is a tick-born zoonosis transmitted by ticks of the genus Ixodes ricinus. After tick bite, the risk of transmission of an infectious agent remains low, most often represented by Borrelia burgdorferi sensu lato; co-infections in Humans by several different infectious agents (bacterial, viral or parasitic) are possible but a priori rare. In addition, besides well-known tick-borne pathogens, new species or gender of micro-organisms are regularly described in ticks but their pathogenicity in human pathology is not described or not yet established. The clinical presentation of Lyme borreliosis is varied, with localized and disseminated forms occurring long ago after tick bite, making diagnosis sometimes difficult. The natural course of Lyme borreliosis is insufficiently known because of recommendations of antibiotherapy in case of illness; however, some historical studies seem reassuring with possible spontaneous healing and seemingly minor sequelae. The diagnosis of disseminated forms requires paraclinical examinations, in first place serology, whose sensitivity increases with time of evolution of borreliosis; this is all the more interesting as the disseminated forms are of more difficult clinical diagnosis. After antibiotherapy, the clinical course is good, the sequelae remain possible especially in case of late diagnosis or late disseminated form; however, their frequency remains unknown.
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http://dx.doi.org/10.3917/spub.190.0051DOI Listing
May 2019

Portraying infective endocarditis: results of multinational ID-IRI study.

Eur J Clin Microbiol Infect Dis 2019 Sep 11;38(9):1753-1763. Epub 2019 Jun 11.

Department of Infectious Diseases and Clinical Microbiology, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey.

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).
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http://dx.doi.org/10.1007/s10096-019-03607-xDOI Listing
September 2019

Comment on "Effect of Artemisia annua and Artemisia afra tea infusions on schistosomiasis in a large clinical trial".

Phytomedicine 2019 09 25;62:152804. Epub 2018 Dec 25.

GMRC, Service de Santé Publique, Université de Strasbourg, CHU de Strasbourg. iCUBE, UMR7357, 67000 Strasbourg, France.

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http://dx.doi.org/10.1016/j.phymed.2018.12.027DOI Listing
September 2019