22 research outputs found
Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA.
Background In angioimmunoblastic T-cell lymphoma, symptoms linked to B-lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts, often infected by Epstein-Barr virus, are found in tumor tissues. We postulated that the disruption of putative B-T interactions and/or depletion of the Epstein-Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could improve the clinical outcome produced by conventional chemotherapy. DESIGN AND METHODS: Twenty-five newly diagnosed patients were treated, in a phase II study, with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B-blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were fully characterized at diagnosis and were correlated with clinical outcome. RESULTS: A complete response rate of 44% (95% CI, 24% to 65%) was observed. With a median follow-up of 24 months, the 2-year progression-free survival rate was 42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%). The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes (P<0.004) and the detection of circulating tumor cells (P=0.0019). Despite peripheral Epstein-Barr virus clearance after treatment, the viral load at diagnosis (>100 copy/ÎŒg DNA) was associated with shorter progression-free survival (P=0.06). Conclusions We report here the results of the first clinical trial targeting both the neoplastic T cells and the microenvironment-associated CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear benefit of adding rituximab to conventional chemotherapy. A strong relationship, not previously described, between circulating Epstein-Barr virus and circulating tumor cells is highlighted
Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA
Incidence of Human Herpesvirus 8 (HHV-8) infection among HIV-uninfected individuals at high risk for sexually transmitted infections
<p>Abstract</p> <p>Background</p> <p>The occurrence of, and risk factors for, HHV-8 infection have yet to be definitively determined, particularly among heterosexual individuals with at-risk behavior for sexually transmitted infections (STI). The objective of this study was to estimate the incidence and determinants of HHV-8 infection among HIV-uninfected individuals repeatedly attending an urban STI clinic.</p> <p>Methods</p> <p>Sera from consecutive HIV-uninfected individuals repeatedly tested for HIV-1 antibodies were additionally tested for HHV-8 antibodies using an immunofluorescence assay. To identify determinants of HHV-8 infection, a nested case-control study and multivariate logistic regression analysis were performed.</p> <p>Results</p> <p>Sera from 456 HIV-uninfected individuals (224 multiple-partner heterosexuals and 232 men who have sex with men (MSM]) were identified for inclusion in the study. The HHV-8 seroprevalence at enrollment was 9.4% (21/224; 95% C.I.: 6.0â14.2%) among heterosexuals with multiple partners and 22.0% (51/232; 95% C.I.: 16.9â28.0%) among MSM. Among the 203 multiple-partner heterosexuals and 181 MSM who were initially HHV-8-negative, 17 (IR = 3.0/100 p-y, 95% C.I.: 1.9 â 4.8) and 21 (IR = 3.3/100 p-y, 95% C.I:.2.1 â 5.1) seroconversions occurred, respectively. HHV-8 seroconversion tended to be associated with a high number of sexual partners during the follow-up among MSM (> 10 partners: AOR = 3.32 95% CI:0.89â12.46) and among the multiple-partner heterosexuals (> 10 partner; AOR = 3.46, 95% CI:0.42â28.2). Moreover, among MSM, HHV-8 seroconversion tended to be associated with STI (AOR = 1.80 95%CI: 0.52â7.96).</p> <p>During the study period the HIV-1 incidence was lower than that of HHV-8 among both groups (0.89/100 p-y among MSM and 0.95/100 p-y among multiple-partner heterosexuals).</p> <p>Conclusion</p> <p>The large difference between the incidence of HHV-8 and the incidence of HIV-1 and other STIs may suggest that the circulation of HHV-8 is sustained by practices other than classical at-risk sexual behavior.</p
Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis
BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London
Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study
Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world.
Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231.
Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05â2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001).
Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication
Archives des Maladies Professionnelles et de l'Environnement
RĂ©sumĂ© Objectif Le devenir professionnel des asthmatiques est souvent dĂ©favorable avec des consĂ©quences frĂ©quentes de lâasthme sur le statut socioĂ©conomique (diminution de revenus et/ou perte de lâemploi). Lâobjectif de ce travail Ă©tait dâĂ©tudier lâitinĂ©raire socioprofessionnel des asthmatiques Ă partir des donnĂ©es de lâenquĂȘte SantĂ© et itinĂ©raire professionnel. MĂ©thodes En 2006, 13 648 individus de 20 à 74 ans vivant en France mĂ©tropolitaine en mĂ©nage ordinaire ont participĂ© Ă lâenquĂȘte. En 2010, ils ont Ă©tĂ© recontactĂ©s et 11 220 individus ont Ă©tĂ© rĂ©interrogĂ©s. La prĂ©sente analyse a portĂ© sur les 11 068 individus ayant participĂ© aux deux vagues de lâenquĂȘte et ayant un itinĂ©raire professionnel. Lâasthme aux diffĂ©rents moments de la vie a Ă©tĂ© repĂ©rĂ© par les dĂ©clarations des individus. Les antĂ©cĂ©dents professionnels et mĂ©dicaux ont Ă©tĂ© recueillis. RĂ©sultats Chez les femmes, aprĂšs ajustement sur lâĂąge, la probabilitĂ© dâĂȘtre asthmatique Ă©tait plus Ă©levĂ©e chez celles ayant eu au moins une pĂ©riode de chĂŽmage au cours de leur itinĂ©raire professionnel, une durĂ©e de pĂ©riodes de chĂŽmage de plus dâun an et une durĂ©e dâemploi plus courte, et Ă©tait plus faible chez celles ayant les revenus les plus Ă©levĂ©s. Entre 2006 et 2010, les femmes asthmatiques ont connu plus frĂ©quemment des pĂ©riodes de chĂŽmage et des arrĂȘts maladie que les non-asthmatiques. Aucune diffĂ©rence statistiquement significative nâĂ©tait observĂ©e chez les hommes. Conclusions Ces rĂ©sultats suggĂšrent que les femmes asthmatiques comparĂ©es au non-asthmatiques, connaissent des parcours professionnels plus instables et ont des revenus infĂ©rieurs, ce qui nâest pas observĂ© chez les hommes. Les cohortes Coset et Constances devraient permettre dâĂ©tudier plus en dĂ©tail lâimpact de lâasthme sur la carriĂšre professionnelle des travailleurs. Summary Purpose of the study The working life of people with asthma and the consequences of asthma on their socio-economic status are often unfavorable (decreased income and/or loss of employment). The objective of our analysis was to study the socio-professional itinerary of asthmatic people using data from SantĂ© et ItinĂ©raire Professionnel survey. Methods In 2006, 13,648 individuals aged 20 to 74 years living in France participated in the survey, among whom 11,220 individuals were re-interviewed in 2010. Our study population included 11,068 persons who participated in both phases of the survey and had a occupational itinerary. Asthma at different times of life was identified through individualsâ reporting. Data on occupational and medical history were collected. Results In women, the age-adjusted probability of having asthma was higher in those with at least one period of unemployment during their working life, a period of unemployment of more than one year, and a shorter duration of employment. It was lower in those with the highest incomes. Between 2006 and 2010, women with asthma experienced more often periods of unemployment and sick leave than non-asthmatics. In men, no significant difference was observed. Conclusion These results suggest that asthmatic women experience a more unstable working life and have lower incomes as compared to non-asthmatics, which is not observed in men. The ongoing Coset and Constances cohorts would allow to assess more deeply the impact of asthma on the working life