CRP under 130 mg/L rules out the diagnosis of Legionella pneumophila serogroup 1 (URINELLA Study).

INTRODUCTION: In case of pneumonia, some biological findings are suggestive for Legionnaire's disease (LD) including C-reactive protein (CRP). A low level of CRP is predictive for negative Legionella Urinary-Antigen-Test (L-UAT). METHOD: Observational retrospective study in Nord-Franche-Comté Hospital with external validation in Besançon University Hospital, France which included all adults with L-UAT performed during January 2018 to December 2022. The objective was to determine CRP optimal threshold to predict a L-UAT negative result. RESULTS: URINELLA included 5051 patients (83 with positive L-UAT). CRP optimal threshold was 131.9 mg/L, with a negative predictive value (NPV) at 100%, sensitivity at 100% and specificity at 58.0%. The AUC of the ROC-Curve was at 88.7% (95% CI, 86.3-91.1). External validation in Besançon Hospital patients showed an AUC at 89.8% (95% CI, 85.5-94.1) and NPV, sensitivity and specificity was respectively 99.9%, 97.6% and 59.1% for a CRP threshold at 131.9 mg/L; after exclusion of immunosuppressed patients, index sensitivity and NPV reached also 100%. CONCLUSION: In case of pneumonia suspicion with a CRP level under 130 mg/L (independently of the severity) L-UAT is useless in immunocompetent patients with a NPV at 100%. We must remain cautious in patients with symptoms onset less than 48 h before CRP dosage.

Outbreak of Mycoplasma pneumoniae pneumonia in hospitalized patients: Who is concerned? Nord Franche-Comté Hospital, France, 2023-2024.

We report an outbreak of confirmed Mycoplasma pneumoniae community-acquired pneumonia (CAP) in Nord Franche-Comté Hospital, France, from 14 November 2023 to 31 January 2024. All 13 inpatients (11 adults with a mean age of 45.5 years and 2 children) were diagnosed with positive serology and/or positive reverse transcription polymerase chain reaction (RT-PCR) on respiratory specimens. All patients were immunocompetent and required oxygen support with a mean duration of oxygen support of 6.2 days. Two patients were transferred to the intensive care unit (ICU) but were not mechanically ventilated. Patients were treated with macrolides (n = 12, 92.3%) with recovery in all cases. No significant epidemiological link was reported in these patients.

Orf Nodule with Erythema Multiforme during a Monkeypox Outbreak, France, 2022.

A 26-year-old patient in France who worked as a butcher sought care initially for erythema multiforme. Clinical examination revealed a nodule with a crusty center, which upon investigation appeared to be an orf nodule. Diagnosis was confirmed by PCR. The patient was not isolated and had a favorable outcome after basic wound care.

Campylobacter fetus Invasive Infections and Risks for Death, France, 2000-2021.

Campylobacter fetus accounts for 1% of Campylobacter spp. infections, but prevalence of bacteremia and risk for death are high. To determine clinical features of C. fetus infections and risks for death, we conducted a retrospective observational study of all adult inpatients with a confirmed C. fetus infection in Nord Franche-Comté Hospital, Trevenans, France, during January 2000-December 2021. Among 991 patients with isolated Campylobacter spp. strains, we identified 39 (4%) with culture-positive C. fetus infections, of which 33 had complete records and underwent further analysis; 21 had documented bacteremia and 12 did not. Secondary localizations were reported for 7 (33%) patients with C. fetus bacteremia, of which 5 exhibited a predilection for vascular infections (including 3 with mycotic aneurysm). Another 7 (33%) patients with C. fetus bacteremia died within 30 days. Significant risk factors associated with death within 30 days were dyspnea, quick sequential organ failure assessment score >2 at admission, and septic shock.

Positive intrathecal anti-Borrelia antibody synthesis: what are the implications for clinical practice? Clinical features and outcomes of 138 patients in a French multicenter cohort study.

We aimed to describe the clinical characteristics, management, and residual symptoms (RS) in patients with definite and possible Lyme neuroborreliosis (LNB). We conducted a retrospective French multicenter cohort study (2010-2020). Cases of LNB were defined as clinical manifestations attributed to LNB and a positive Borrelia-specific intrathecal antibody index (AI) ("possible" LNB) and with pleocytosis ("definite" LNB). Risk factors of RS were determined using a logistic regression model. We included 138 adult patients with a positive AI. Mean age was 59.5 years (± 14.7). The median duration of symptoms before diagnosis was 1.0 [0.5-4.0] months. The most frequent manifestation was radicular pain (n = 79, 57%). Complete cerebrospinal fluid (CSF) leukocyte analysis was available in 131 patients, of whom 72 (55%) had pleocytosis. Patients with definite LNB had a shorter duration of symptoms (median 1.0 [0.5-2.6] vs. 3.0 [0.6-7.0] months, p < 0.01) and more radicular pain (74% vs 44%, p < 0.01) than patients with possible LNB. At the last visit (median duration of follow-up: 70 [30-175] days), 74/124 patients (59.7%) reported RS, mostly radicular pain (n = 31, 25%). In multivariate analysis, definite LNB (OR = 0.21 [0.05-0.931], p = 0.039) and duration of symptoms less than 3 months (OR = 0.04 [0.01-0.37], p = 0.005) were protective factors against RS at last follow-up. Our study highlights the challenges of LNB management, especially for patients with a positive AI without pleocytosis, questioning whether LB is still ongoing or not. Early diagnosis and treatment are important to improve outcomes and to lower potential RS.

Tocilizumab in COVID-19 pneumonia: Practical proposals based on a narrative review of randomised trials.

In this article, we express our opinion about tocilizumab as an effective treatment in coronavirus disease 2019, based on a narrative review and a deep analysis of tocilizumab randomised trial results. Eight trials were included. No one was in favour for controlled arm about main endpoint of death or mechanical ventilation incidence at day 28-30. Five trials on heterogenous populations seem to not demonstrate tocilizumab efficacy, but showed encouraging results in subgroup analysis on severe/critical patients (in favour for tocilizumab). Trials on severe/critical COVID-19 pneumonia as REMAP-CAP and RECOVERY showed mortality benefit of tocilizumab administration; CORIMUNO, REMAP-CAP and RECOVERY showed that tocilizumab decreased the incidence of mechanical ventilation. No safety signal about tocilizumab used was noticed in all trials. We concluded that tocilizumab reduces mortality and mechanical ventilation requirement if administered with the right timing in COVID-19 pneumonia. The challenge now is to define the optimal group and timing for tocilizumab benefit and we suggest that: (i) tocilizumab has a place in treatment of severe/critical COVID-19 pneumonia, with a high level of O2 flow or noninvasive ventilation or high flow nasal cannula; (ii) possibly early after intubation in patients on mechanical ventilation. Initiating tocilizumab in critically ill patients early before irreversible respiratory failure, especially in patients at an inflammatory stage could be the key to successful outcome.

Increased COVID-19 Severity among Pregnant Patients Infected with SARS-CoV-2 Delta Variant, France.

We conducted a retrospective study of pregnant persons hospitalized for severe acute respiratory syndrome coronavirus 2 infection in France. Delta variant infection had a relative risk of 14.33 for intensive care unit admission and 9.56 for high supplemental oxygen support. The Delta variant might cause more severe illness during pregnancy.

Olfactory dysfunction in COVID-19, new insights from a cohort of 353 patients: The ANOSVID study.

Olfactory disorders (OD) pathogenesis, underlying conditions, and prognostic in coronavirus disease 2019 (COVID-19) remain partially described. ANOSVID is a retrospective study in Nord Franche-Comté Hospital (France) that included COVID-19 patients from March 1 2020 to May 31 2020. The aim was to compare COVID-19 patients with OD (OD group) and patients without OD (no-OD group). A second analysis compared patients with anosmia (high OD group) and patients with hyposmia or no OD (low or no-OD group). The OD group presented less cardiovascular and other respiratory diseases compared to the no-OD group (odds ratio [OR] = 0.536 [0.293-0.981], p = 0.041 and OR = 0.222 [0.056-0.874], p = 0.037 respectively). Moreover, history of malignancy was less present in the high OD group compared with the low or no-OD group (OR = 0.170 [0.064-0.455], p < 0.001). The main associated symptoms (OR > 5) with OD were loss of taste (OR = 24.059 [13.474-42.959], p = 0.000) and cacosmia (OR = 5.821 [2.246-15.085], p < 0.001). Most of all ORs decreased in the second analysis, especially for general, digestive, and ENT symptoms. Only two ORs increased: headache (OR = 2.697 [1.746-4.167], p < 0.001) and facial pain (OR = 2.901 [1.441-5.842], p = 0.002). The high OD group had a higher creatinine clearance CKD than the low or no-OD group (89.0 ± 21.1 vs. 81.0 ± 20.5, p = 0.040). No significant difference was found concerning the virological, radiological, and severity criteria. OD patients seem to have less comorbidity, especially better cardiovascular and renal function. Associated symptoms with OD were mostly neurological symptoms. We did not find a significant relationship between OD and less severity in COVID-19 possibly due to methodological bias.

Extreme gonococcal susceptibility associated with acquired complement deficiency secondary to hypocomplementemic urticarial vasculitis and systemic lupus erythematosus.

Gonococcal infection is rarely associated with septic shock. We describe a recurrent case of septic shock related to disseminated gonococcemia in a patient with systemic lupus erythematosus and hypocomplementemic urticarial vasculitis, and discuss the implication of profound acquired complement deficiency secondary to these auto-immune diseases. This case raises the question of systematic antibioprophylaxis in patients with acquired complement deficiency.

Massive vulvar edema revealing idiopathic systemic capillary leak syndrome.

Idiopathic systemic capillary leak syndrome is a rare disease characterized by recurrent episodes of hypotension, hypoalbuminemia and peripheral edema caused by capillary hyperpermeability with approximately 350 documented cases worldwide. We report herein the case of a 22-year-old primiparous patient with an unusual compartment syndrome represented with spontaneous massive vulvar edema. Treatment consisted of volume replacement and intravenous polyvalent immunoglobulins perfusions. Vulvar edema was treated surgically by incision and drainage with favorable outcome. The pregnancy follow-up did not show any fetal abnormalities. The childbirth at 35 weeks was natural and the newborn was healthy.

Pauci-symptomatic foodborne botulism due to Clostridium botulinum type B with predominant ophthalmologic presentation possibly after consumption of honey.

Foodborne botulism, a toxin-mediated illness caused by Clostridium botulinum, is a public health emergency, and rarely reported in France. We report herein the case of two family members (a father and his son) from Franche-Comté, France, presented with ophthalmological symptoms which occurred after non-specific gastro-intestinal symptoms after a trip to Serbia with a recent consumption of artisanal honey, and suggestive of botulism. The suspected intoxication appeared to be caused by a type B strain of C. botulinum, as demonstrated by toxin-neutralization in the lethal mouse bioassay. Regarding the mild-to-moderate form, the patients were treated symptomatically with monitoring, against antitoxins, with no evidence of relapse afterwards. We want to highlight the importance of recognizing clinical ophthalmologic botulism symptoms as unreactive bilateral mydriasis with lack of accommodation to contribute to earlier diagnosis in case of pauci-symptomatic botulism.

Successful benralizumab for eosinophilic myocarditis in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is characterised by many features, including asthma, allergic rhinitis, peripheral and tissue eosinophilia, and vasculitis. Its pathophysiology is still unclear and we suggest that there are different phenotypes of EGPA, which may respond differently to available treatments. Within the most promising targeting biotherapy, benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, has proved both highly effective and safe. We report herewith a case of EGPA presenting a myocarditis relapse successfully treated with benralizumab.

Acute Cerebral Stroke with Multiple Infarctions and COVID-19, France, 2020.

We describe 2 cases in coronavirus disease patients in France involving presumed thrombotic stroke that occurred during ongoing anticoagulation treatment for atrial fibrillation stroke prophylaxis; 1 patient had positive antiphospholipid antibodies. These cases highlight the severe and unique consequences of coronavirus disease-associated stroke.

Biomarker variation in patients successfully treated with tocilizumab for severe coronavirus disease 2019 (COVID-19): results of a multidisciplinary collaboration.

OBJECTIVES: Acute respiratory distress syndrome (ARDS) related to SARS-CoV-2 is likely due to a cytokine storm characterised by a major release of pro-inflammatory cytokines, including interleukin-6 (IL-6). Blocking excessive IL-6 production might be the key to the COVID-19-ARDS treatment. Beneficial effects of IL-6 blockade using a humanised anti-IL-6 receptor antibody, tocilizumab (TCZ) were previously reported in patients with COVID-19 related ARDS. The aim of the study was to study the variation over time of several biomarkers, demonstrated to be predictors of poor prognostic, in subjects successfully treated with TCZ for severe COVID-19. METHODS: Retrospective analysis of a case series of patients with COVID-19-ARDS, evidenced by RT-PCR and lung CT-scan. Patients with increasing O2 requirements, within the window of opportunity for TCZ treatment (Day 7 to Day 17 after onset of symptoms) were treated with TCZ (2 infusions of 8 mg/kg). Demographic, biological and clinical data were collected from the patients' files. Serum levels of CRP, ferritin, fibrinogen, lymphocytes, platelets, creatinine, D-dimer and liver enzymes were assayed at the time of the first TCZ administration, then every two days for 8 days. RESULTS: 40 patients were treated with TCZ. Most of them had several comorbidities, and all had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer, liver enzymes). 30 patients (75%) benefited from TCZ and 10 patients died. In the survivors, following TCZ administration CRP decreased dramatically as early as day 4 (-86.7%, p<0.0001) and returned to normal at day 6. Fibrinogen and lymphocyte count returned to normal values at day 6. Ferritin also decreased significantly. No significant change was observed for D-dimer (p=0.68) and other studied biomarkers (haemoglobin, leucocyte count, AST). CONCLUSIONS: In patients with COVID-19 acute respiratory distress syndrome, treatment with TCZ resulted in favourable evolution in 75% of the cases. Biomarkers of inflammation (CRP, ferritin, fibrinogen) decreased dramatically as early as the 4th day after TCZ injection. Lymphopenia, a predictor of poor prognostic, was reversed 6 days after TCZ injection.