Systemic inflammatory cytokine profiles in patients with gout during flare, intercritical and treat-to-target phases: TNFSF14 as new biomarker.

INTRODUCTION: Untreated gout is characterised by monosodium urate (MSU) crystal accumulation responsible for recurrent flares that are commonly separated by asymptomatic phases. Both phases are inflammatory conditions of variable intensity. Gout flares are self-limited inflammatory reactions involving multiple mediators. This study aimed to characterise the inflammatory profiles of gout at different phases. METHODS: Using the Olink targeted proteomics, levels of 92 inflammation-related proteins were measured in plasma samples of a prospective gout population (GOUTROS), collected at gout flare (T1), the intercritical phase (T2) and after reaching the target serum urate level under urate-lowering therapy (T3). Results were validated in an independent cohort (OLT1177-05) with plasmas collected at T1 and T2. Ex vivo and in vitro experiments were performed to assess the inflammatory properties of new biomarkers. RESULTS: In total, 21 inflammatory new biomarkers were differentially expressed during the three time-points of gout disease. The levels of four of these proteins (interleukin 6 (IL-6), colony-stimulating factor 1, vascular endothelial growth factor A and tumour necrosis factor superfamily 14 (TNFSF14)) were increased during gout flare in an independent cohort. IL-6 and TNFSF14 had the highest fold change in expression during T1 versus T2 or T3. TNFSF14 was produced at the inflamed joint and enhanced the inflammatory response induced by lipopolysaccharide and MSU crystal stimulation. Conversely, TNFSF14 blockade reduced the inflammatory response. Additionally, single nucleotide polymorphisms of TNFSF14 affected the ability of myeloid cells to produce inflammatory cytokines. CONCLUSION: Gout flare involves multiple inflammatory mediators that may be used as potential therapeutic targets.

Antimicrobial for 7 or 14 Days for Febrile Urinary Tract Infection in Men: A Multicenter Noninferiority Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

BACKGROUND: The optimal duration of antimicrobial therapy for urinary tract infections (UTIs) in men remains controversial. METHODS: To compare 7 days to 14 days of total antibiotic treatment for febrile UTIs in men, this multicenter randomized, double-blind. placebo-controlled noninferiority trial enrolled 282 men from 27 centers in France. Men were eligible if they had a febrile UTI and urine culture showing a single uropathogen. Participants were treated with ofloxacin or a third-generation cephalosporin at day 1, then randomized at day 3-4 to either continue ofloxacin for 14 days total treatment, or for 7 days followed by placebo until day 14. The primary endpoint was treatment success, defined as a negative urine culture and the absence of fever and of subsequent antibiotic treatment between the end of treatment and 6 weeks after day 1. Secondary endpoints included recurrent UTI within weeks 6 and 12 after day 1, rectal carriage of antimicrobial-resistant Enterobacterales, and drug-related events. RESULTS: Two hundred forty participants were randomly assigned to receive antibiotic therapy for 7 days (115 participants) or 14 days (125 participants). In the intention-to-treat analysis, treatment success occurred in 64 participants (55.7%) in the 7-day group and in 97 participants (77.6%) in the 14-day group (risk difference, -21.9 [95% confidence interval, -33.3 to -10.1]), demonstrating inferiority. Adverse events during antibiotic therapy were reported in 4 participants in the 7-day arm and 7 in the 14-day arm. Rectal carriage of resistant Enterobacterales did not differ between both groups. CONCLUSIONS: A treatment with ofloxacin for 7 days was inferior to 14 days for febrile UTI in men and should therefore not be recommended. CLINICAL TRIALS REGISTRATION: NCT02424461; Eudra-CT: 2013-001647-32.

COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters.

Whereas recent investigations have revealed viral, inflammatory, and vascular factors involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung pathogenesis, the pathophysiology of neurological disorders in coronavirus disease 2019 (COVID-19) remains poorly understood. Olfactory and taste dysfunction are common in COVID-19, especially in mildly symptomatic patients. Here, we conducted a virologic, molecular, and cellular study of the olfactory neuroepithelium of seven patients with COVID-19 presenting with acute loss of smell. We report evidence that the olfactory neuroepithelium is a major site of SARS-CoV2 infection with multiple cell types, including olfactory sensory neurons, support cells, and immune cells, becoming infected. SARS-CoV-2 replication in the olfactory neuroepithelium was associated with local inflammation. Furthermore, we showed that SARS-CoV-2 induced acute anosmia and ageusia in golden Syrian hamsters, lasting as long as the virus remained in the olfactory epithelium and the olfactory bulb. Last, olfactory mucosa sampling from patients showing long-term persistence of COVID-19-associated anosmia revealed the presence of virus transcripts and of SARS-CoV-2-infected cells, together with protracted inflammation. SARS-CoV-2 persistence and associated inflammation in the olfactory neuroepithelium may account for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management of this disease.

Emergency department diagnosis and management of skin diseases with real-time teledermatologic expertise.

IMPORTANCE: Skin conditions are a common reason for patients to consult emergency department (ED) physicians. OBJECTIVE: To evaluate real-time teledermatologic expertise with the use of mobile telephones for the diagnosis and management of skin conditions in patients seen in the ED. DESIGN, SETTING, AND PARTICIPANTS: This observational study of adults who consecutively consulted in the ED for a dermatologic condition was conducted under routine conditions in the ED from May 1, 2008, through June 30, 2010. MAIN OUTCOMES AND MEASURES: Diagnosis agreement and management concordance. RESULTS: One hundred eleven patients were enrolled in the study. Eighty-three patients (74.8%) were evaluated using videoconferencing. Dermatologic remote expertise invalidated, enlarged, or clarified ED physicians' diagnosis and management in 75 of 110 cases (68.2%). Videoconferencing improved the diagnostic performance in 57 of 83 cases (68.7%) (P < 10(-4)). Management concordance was moderate between ED physicians and dermatologists for specialist consultation within 24 hours (κ, 0.49; 95% CI, 0.14-0.84) and immediate hospitalization (κ, 0.49; 95% CI, 0.41-0.57). Patients were significantly more often discharged by dermatologists (46.8% vs 39.1%) (P < 10(-4)). CONCLUSIONS AND RELEVANCE: Compared with standard hardware, new-generation mobile devices reduce the cost of videoconferencing, increase the versatility of teledermatology, and decrease general practitioner investment time.

[Proposal of HIV, HBV and HCV targeted screening: short period feasibility study in a free-access outpatient medical structure]. / Faisabilité du dépistage ciblé VIH, VHB, VHC dans une structure de soins ambulatoires avec un système de permanence d'accès aux soins de santé intégré

OBJECTIVES: In France, patients coming from sub-Saharan Africa, French Indies and French Guiana are frequently missed HIV, HBV and HCV diagnosis, despite high prevalence of these infections. METHODS: Targeted proposal of HIV, HBV and HCV screening, using sensitive enzyme immunoassays, to any adult patient originating of the above mentioned areas, with/without medical insurance, consulting for a medical issue in outpatients' department. Monocentric prospective study in a hospital in Paris during 28 consecutive days in 2010. RESULTS: Among the 272 eligible patients, 166 were tested (patients' acceptance: 61%). 180/272 (66%) alleged being tested previously for HIV, women (66/87, 76%) more frequently than men (114/185, 62%), P=0.02. Patients' acceptance seemed higher in patients mentioning no previous test than in patients reporting previous test. Among the patients who refused being tested, reporting a previous negative HIV test, more than a quarter has been tested more than 1 year ago. Among the 166 tested patients, 120 (72%) came back to get their results, men (89/113, 79%) more frequently than women (31/53, 58.5%), P=0.009; recently metropolitan patients more frequently than longer metropolitan patients, P=0.01; patients without any job more frequently than patients with a job, P=0.01. Three (1.8%) HIV tests returned positive; HBsAg was positive in 13 (7.8%) patients; 54 patients (32.7%) had a negative hepatitis B screening (anti-HBcAb+HBsAg+anti-HBsAb), attesting to sensitivity to this infection, only 18 patients (10.9%) showed isolated anti-HBsAb at protective levels. Eighty-one patients (49.1%) exhibited anti-HBcAb, confirming the high prevalence of HBV infection in the areas the patients came from. Six patients (3.6%) had anti-HCVAb. There was no co-infection. CONCLUSION: Targeted HIV, HBV and HCV screening to patients coming from high prevalence areas in outpatients' department appears a very cost-effective strategy.