Atypical Vogt-Koyanagi-Harada disease or new uveomeningitic syndrome?

Purpose: To report on a patient affected by bilateral intermediate uveitis (IU) as the initial sign of an uveomeningitic syndrome. Methods: Thorough history, physical examination and ancillary laboratory and radiological testing were performed in this observational case study. Results: A 23-year-old Caucasian man developed bilateral IU, primarily diagnosed as "idiopathic” since a detailed etiologic work-up was not indicative of underlying disease. Seven months later, he presented with poliosis and vitiligo. Lumbar puncture revealed cerebrospinal fluid pleocytosis. Optical coherence tomography showed bilateral subclinical macular edema (ME). The visual acuity was still 20/20 in both eyes. Clinical, laboratory and radiological results did not fit into any known syndrome. Conclusions: According to all the tests performed, the disease in our patient is a uveomeningitic disease with IU and ME which could be interpreted as an atypical form of Vogt-Koyanagi-Harada disease or a new uveomeningitic syndrome because there is no evidence for any other known diseas

Mepolizumab and benralizumab in patients with severe asthma and a history of eosinophilic granulomatosis with polyangiitis

IntroductionAsthma associated with eosinophilic granulomatosis with polyangiitis (EGPA) is often severe and corticosteroid-dependent, leading to significant morbidity. Mepolizumab and benralizumab are humanized monoclonal antibodies targeting interleukin 5 (IL-5) and its receptor, respectively. They have been shown to be effective in steroid-sparing in patients with severe eosinophilic asthma.ObjectiveOur aim was to evaluate the efficacy and safety of mepolizumab and benralizumab prescribed for severe asthma in patients with EGPA under “real-world” conditions.MethodsThis was a retrospective analysis of patients with EGPA and persistent asthma who received either mepolizumab 100 or 300 mg administered every 4 weeks, or benralizumab 30 mg administered every 4 weeks for the initial 3 injections and followed by an injection every 8 weeks thereafter, whilst combined with oral glucocorticoids. The follow-up every 6 ± 3 months included an assessment of clinical manifestations, pulmonary function tests and eosinophil cell count. The primary outcome was the proportion of patients at 12 months receiving a daily oral dose of prednisone or equivalent of 4 mg or less with a BVAS of 0.ResultsTwenty-six patients were included. After 12 months of treatment with mepolizumab or benralizumab, 32% of patients met the primary outcome and were receiving less than 4 mg of prednisone per day with a BVAS of 0. The median dose of prednisone was 10 mg per day at baseline, 9 mg at 6 months, and 5 mg at 12 months (p ≤ 0.01). At 12 months, 23% of patients were weaned off corticosteroids, while an increase or no change in dose was observed in 27% of patients. The median eosinophil count was significantly reduced from 365 cells/mm3 to 55 cells/mm3 at 6 months and 70 cells/mm3 at 12 months, respectively. No significant change was observed in FEV1. After 12 months of treatment, 14% of patients had had an average of 1 exacerbation of asthma, compared with 52% of patients before baseline. The tolerability profile was favorable.ConclusionIn this real-world study in patients with severe asthma and a history of EGPA asthma, mepolizumab and benralizumab had a significant steroid-sparing effect and reduced asthma exacerbation, but no significant effect on lung function

Development and Validation of a Bedside Score to Predict Early Death in Cancer of Unknown Primary Patients

BACKGROUND: We have investigated predictors of 90-day-mortality in a large cohort of non-specific cancer of unknown primary patients. METHODS: Predictors have been identified by univariate and then logistic regression analysis in a single-center cohort comprising 429 patients (development cohort). We identified four predictors that produced a predictive score that has been applied to an independent multi-institutional cohort of 409 patients (validation cohort). The score was the sum of predictors for each patient (0 to 4). RESULTS: The 90-day-mortality-rate was 33 and 26% in both cohorts. Multivariate analysis has identified 4 predictors for 90-day-mortality: performance status>1 (OR = 3.03, p = 0.001), at least one co-morbidity requiring treatment (OR = 2.68, p = 0.004), LDH>1.5 x the upper limit of normal (OR = 2.88, p = 0.007) and low albumin or protein levels (OR = 3.05, p = 0.007). In the development cohort, 90-day-mortality-rates were 12.5%, 32% and 64% when the score was [0-1], 2 and [3]-[4], respectively. In the validation cohort, risks were 13%, 25% and 62% according to the same score values. CONCLUSIONS: We have validated a score that is easily calculated at the beside that estimates the 90-days mortality rate in non-specific CUP patients. This could be helpful to identify patients who would be better served with palliative care rather than aggressive chemotherapy

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

LYMPHOMES NON HODGKINIENS ET INFECTION PAR LE VIRUS DE L'HEPATITE C (ETUDE CAS-TEMOINS)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

La maladie de Kawasaki chez l'adulte (à propos de 5 cas et revue de la littérature)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Pharmacorésistance et cancer du poumon Non à petites cellules

Au cours de cette thèse, nous avons utilisé une approche immunohistochimique pour évaluer les valeurs pronostiques ou prédictives de protéines respectivement impliquées dans le métabolisme de la gemcitabine et des agents antitubuline dans le cancer du poumon non à petites cellules avancé. Nos résultats montrent que: (1) des faibles niveaux d'expression de cN-II sont les seuls facteurs pronostiques associés à la survie globale chez les patients traités par une chimiothérapie à base de gemcitabine ; (2) un haut niveau d'expression de b-tubuline III est associé à une résistance à la vinorelbine et à un mauvais pronostic chez 93 patients recevant une chimiothérapie à base de vinorelbine ; (3) le niveau d'expression de b-tubuline III est prédictif de la réponse au traitement et du devenir des patients recevant une chimiothérapie par paclitaxel, mais pas un facteur pronostic pour l'ensemble de ces patientsLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Sarcoïdose et cryptococcose (cryptOsarc, une étude comparative à propos de 18 observations)

LYON1-BU Santé (693882101) / SudocSudocFranceF

La sarcoïdose du sujet agé (étude comparative à propos de 30 observations)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Apport du FDG-PET et de la biologie moléculaire dans les fièvres prolongées inexpliquées (à propos d'une série rétrospective de 103 cas)

La prise en charge des fièvres prolongées inexpliquées demeure un défi malgré l'apport des nouveaux outils paracliniques. Des séries récentes suggèrent l'intérêt du PET-scan dans la stratégie diagnostique mais aucune n'a étudié l'apport de' la biologie moléculaire pour le diagnostic des pathologies infectieuses. Nous avons réalisé une étude rétrospective à partir de 1 03 patients afin de préciser l'apport diagnostique de ces outils ainsi que l'évolution clinique et la mortalité de ces patients. Etude rétrospective au sein de 2 services de médecine interne d'un centre hospitalo-universitaire entre 2002 et 2012. Le diagnostic de fièvres prolongées inexpliquées repose sur les critères actualisés par Durack et Street en 1991. Le diagnostic final n'a pas été établi dans 50% des cas (n=52). Les étiologies étaient d'origine infectieuse dans 12% des cas (n=12}, inflammatoires dans 29% des cas (n=30}, tumorale dans 3% des cas (n=3) et diverses dans 6% des cas (n=6). Le taux de mortalité est de 10,5% (n=11) et indépendant de l'existence d'un diagnostic. Le décès est imputable dans 5 cas au tableau clinique et dans 2 cas chez des patients sans diagnostic final. Un PET-scan a été réalisé chez 47% des patients (n=48) et était contributif dans 21% des cas (n=10).Parmi ces 48 patients, 6 résultats de TDM étaient contributifs (12,5%) dont 2 associés à un PET-scan négatif. Aucun facteur prédictif de Pet-scan contributif n'a été identifié .Vingt-huit patients ont bénéficié de techniques de biologie moléculaire dont une seule était contributive au diagnostic (PCR CMV). Comme cela a été observé dans les études récentes, le groupe des patients sans diagnostic rend compte de la majorité des fièvres prolongées inexpliquées et la part de maladies infectieuses diminue. Le rendement du PET -scan est de l'ordre de 20%. L'intérêt de la biologie moléculaire semble mineur. Le taux de mortalité globale observée dans l'étude (10%) et le taux de mortalité dans les groupe avec ou sans diagnostic, respectivement 6% et 4% est conforme aux données de la littérature.LYON1-BU Santé (693882101) / SudocSudocFranceF