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/μg 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

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.: 6.0–14.2%) among heterosexuals with multiple partners and 22.0% (51/232; 95% C.I.: 16.9–28.0%) 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 – 4.8) and 21 (IR = 3.3/100 p-y, 95% C.I:.2.1 – 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:0.89–12.46) and among the multiple-partner heterosexuals (> 10 partner; AOR = 3.46, 95% CI:0.42–28.2). Moreover, among MSM, HHV-8 seroconversion tended to be associated with STI (AOR = 1.80 95%CI: 0.52–7.96).</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

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 1·05–2·37; 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

Résumé Objectif Le devenir professionnel des asthmatiques est souvent défavorable avec des conséquences fréquentes de l’asthme sur le statut socioéconomique (diminution de revenus et/ou perte de l’emploi). L’objectif de ce travail était d’étudier l’itinéraire socioprofessionnel des asthmatiques à partir des données de l’enquête Santé et itinéraire professionnel. Méthodes En 2006, 13 648 individus de 20 à 74 ans vivant en France métropolitaine en ménage ordinaire ont participé à l’enquête. En 2010, ils ont été recontactés et 11 220 individus ont été réinterrogés. La présente analyse a porté sur les 11 068 individus ayant participé aux deux vagues de l’enquête et ayant un itinéraire professionnel. L’asthme aux différents moments de la vie a été repéré par les déclarations des individus. Les antécédents professionnels et médicaux ont été recueillis. Résultats Chez les femmes, après ajustement sur l’âge, la probabilité d’être asthmatique était plus élevée chez celles ayant eu au moins une période de chômage au cours de leur itinéraire professionnel, une durée de périodes de chômage de plus d’un an et une durée d’emploi plus courte, et était plus faible chez celles ayant les revenus les plus élevés. Entre 2006 et 2010, les femmes asthmatiques ont connu plus fréquemment des périodes de chômage et des arrêts maladie que les non-asthmatiques. Aucune différence statistiquement significative n’était observée chez les hommes. Conclusions Ces résultats suggèrent que les femmes asthmatiques comparées au non-asthmatiques, connaissent des parcours professionnels plus instables et ont des revenus inférieurs, ce qui n’est pas observé chez les hommes. Les cohortes Coset et Constances devraient permettre d’étudier plus en détail l’impact de l’asthme sur la carrière 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 Santé et Itinéraire 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 individuals’ 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

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