Prevalencia del síndrome metabólico en población laboral española: registro MESYAS

Introducción y objetivos. Estudiar la prevalencia del síndrome metabólico (SM) en la población laboral activa española y analizar sus diferencias según las categorías laborales. Sujetos y método. Se recogieron los datos de 7.256 trabajadores activos (un 82,4% varones), con una edad media de 45,4 ± 9,8 años, empleados en una factoría de coches y unos grandes almacenes. El diagnóstico del SM se realizó mediante los criterios modificados del ATP-III (se utilizó el índice de masa corporal en lugar del perímetro abdominal). Resultados. La prevalencia bruta del SM fue del 10,2%. Ajustada por edad y sexo en una población plana (20-60 años) fue del 5,8% (intervalo de confianza [IC] del 95%, 4,1-7,6%), significativamente más alta en varones que en mujeres (el 8,7%; IC del 95%, 7,3-10,0 frente al 3,0%; IC del 95%, 0,8-5,1). Todos los componentes del SM fueron significativamente más prevalentes en varones, excepto las concentraciones de lipoproteínas de alta densidad, que fueron más bajas. La prevalencia aumentó con la edad y el sexo masculino (odds ratio [OR] = 1,7), la obesidad (OR = 9,6), la hipertensión (OR = 3,4) y la diabetes (OR = 15,4). Los trabajadores manuales presentaron la mayor prevalencia de SM (11,8%), seguidos por EPIDEMIOLOGÍA Y PREVENCIÓN Prevalencia del síndrome metabólico en población laboral española: registro MESYAS Eduardo Alegríaa, Alberto Corderoa, Martín Laclaustrab, Alberto Grimac, Montserrat Leónb, José A. Casasnovasb, Emilio Luengod, Alfonso del Ríob e Ignacio Ferreirab, en representación de los investigadores del registro MESYAS* aDepartamento de Cardiología. Clínica Universitaria de Navarra. Pamplona. Navarra. España. bUnidad de Investigación Cardiovascular. Hospital Clínico Universitario. Zaragoza. España. cServicio de Cardiología Preventiva. Asepeyo. Valencia. España. dServicio de Cardiología. Hospital Militar. Zaragoza. España. *Al final del artículo se relacionan los miembros del equipo de investigación MESYAS. Martín Laclaustra está contratado como investigador en el Instituto Aragonés de Ciencias de la Salud dentro del programa de ayudas a contratos para investigadores que han finalizado su formación médica especializada del Instituto de Salud Carlos III. El registro MESYAS cuenta con una beca de la Sociedad Española de Cardiología (Sevilla, 2003) y la Sección de Cardiología Preventiva y Rehabilitadora. Correspondencia: Dr. E. Alegría Ezquerra. Departamento de Cardiología. Clínica Universitaria de Navarra. Avda. Pío XII, 36. 31008 Pamplona. Navarra. España. Correo electrónico: [email protected] Recibido el 5 de octubre de 2004. Aceptado para su publicación el 18 de marzo de 2005. los trabajadores de oficina (9,3%) y los directivos (7,7%) (gradiente social inverso). Los trabajadores manuales tienen un riesgo superior de presentar SM, con independencia de la edad y el sexo (OR = 1,3); este efecto parece depender de las concentraciones de triglicéridos. Conclusiones. Uno de cada 10 trabajadores activos tiene SM; la prevalencia aumenta con la edad y el sexo masculino. La obesidad y la diabetes suponen gran incremento de la prevalencia. Los trabajadores manuales son el colectivo con mayor prevalencia

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

Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B)

Background The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparison with cyclophosphamide, doxorubicin, vincristin and prednisone plus radiotherapy for young patients with localized diffuse large B-cell lymphoma (DLBCL) was previously demonstrated. We report the results of a trial which evaluates the role of rituximab combined with ACVBP (R-ACVBP) in these patients. Patients and methods Untreated patients younger than 66 years with stage I or II DLBCL and no adverse prognostic factors of the age-adjusted International Prognostic Index were randomly assigned to receive three cycles of ACVBP plus sequential consolidation with or without the addition of four infusions of rituximab. Results A total of 223 patients were randomly allocated to the study, 110 in the R-ACVBP group and 113 in the ACVBP group. After a median follow-up of 43 months, our 3-year estimate of event-free survival was 93% in the R-ACVBP group and 82% in the ACVBP group (P = 0.0487). Three-year estimate of progression-free survival was increased in the R-ACVBP group (95% versus 83%, P = 0.0205). Overall survival did not differ between the two groups with a 3-year estimates of 98% and 97%, respectively (P = 0.686). Conclusion In young patients with low-risk localized DLBCL, rituximab combined with three cycles of ACVBP plus consolidation is significantly superior to ACVBP plus consolidation alon

PHASED VARIANTS IMPROVE DLBCL MINIMAL RESIDUAL DISEASE DETECTION AT THE END OF THERAPY

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Efficacy and safety assessment of prolonged maintenance with subcutaneous rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma: results of the phase III MabCute study

Rituximab plus chemotherapy induction followed by rituximab maintenance for up to 2 years confers a long-term benefit in terms of progression-free survival in patients with indolent non-Hodgkin lymphoma. It is not known whether further prolonged maintenance with rituximab provides additional benefit. The phase III MabCute study enrolled 692 patients with relapsed or refractory indolent non-Hodgkin lymphoma. Patients who responded to induction with rituximab plus chemotherapy and were still responding after up to 2 years’ initial maintenance with subcutaneous rituximab were randomized to extended maintenance with subcutaneous rituximab (n=138) or observation only (n=138). The primary endpoint of investigator-assessed progression-free survival in the randomized population was un-addressed by the end of study because of an insufficient number of events (129 events were needed for 80% power at 5% significance if approximately 330 patients were randomized). In total, there were 46 progression-free survival events, 19 and 27 in the rituximab and observation arms, respectively (P=0.410 by stratified log-rank test; hazard ratio 0.76 [95% confidence interval: 0.37– 1.53]). The median progression-free survival was not reached in either randomized arm. There were no new safety signals; however, adverse events were seen slightly more frequently with rituximab than with observation during extended maintenance. Maintenance for up to 2 years with rituximab after response to initial induction therefore remains the standard of care in patients with relapsed or refractory indolent non- Hodgkin lymphoma. (Clinicaltrials.gov identifier: NCT01461928).</jats:p

A novel series of compositionally biased substitution matrices for comparing Plasmodium proteins

<p>Abstract</p> <p>Background</p> <p>The most common substitution matrices currently used (BLOSUM and PAM) are based on protein sequences with average amino acid distributions, thus they do not represent a fully accurate substitution model for proteins characterized by a biased amino acid composition. This problem has been addressed recently by adjusting existing matrices, however, to date, no empirical approach has been taken to build matrices which offer a substitution model for comparing proteins sharing an amino acid compositional bias. Here, we present a novel procedure to construct series of symmetrical substitution matrices to align proteins from similarly biased <it>Plasmodium </it>proteomes.</p> <p>Results</p> <p>We generated substitution matrices by selecting from the BLOCKS database those multiple alignments with a compositional bias similar to that of <it>P. falciparum </it>and <it>P. yoelii </it>proteins. A novel 'fuzzy' clustering method was adopted to group sequences within these alignments, showing that this method retains more complete information on the amino acid substitutions when compared to hierarchical clustering. We assessed the performance against the BLOSUM62 series and showed that the usage of our matrices results in an improvement in the performance of BLAST database searches, greatly reducing the number of false positive hits. We then demonstrated applications of the use of novel matrices to improve the annotation of homologs between the two <it>Plasmodium </it>species and to classify members of the <it>P. falciparum </it>RIFIN/STEVOR family.</p> <p>Conclusion</p> <p>We confirmed that in the case of compositionally biased proteins, standard BLOSUM matrices are not suited for optimal alignments, and specific substitution matrices are required. In addition, we showed that the usage of these matrices leads to a reduction of false positive hits, facilitating the automatic annotation process.</p

A phase 1/2, open-label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma

Patients with relapsed or refractory lymphoma have limited treatment options, requiring newer regimens. In this Phase 1/2 study (NCT03769181), we assessed the safety, efficacy, and pharmacokinetics of isatuximab (Isa, anti-CD38 antibody) in combination with cemiplimab (Cemi, anti-programmed death-1 [PD-1] receptor antibody; Isa&nbsp;+&nbsp;Cemi) in patients with classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), and peripheral T-cell lymphoma (PTCL). In Phase 1, we characterized the safety and tolerability of Isa&nbsp;+&nbsp;Cemi with planned dose de-escalation to determine the recommended Phase 2 dose (RP2D). Six patients in each cohort were treated with a starting dose of Isa&nbsp;+&nbsp;Cemi to determine the RP2D. In Phase 2, the primary endpoints were complete response in Cohort A1 (cHL anti-PD-1/programmed death-ligand 1 [PD-L1] naïve), and objective response rate in Cohorts A2 (cHL anti-PD-1/PD-L1 progressors), B (DLBCL), and C (PTCL). An interim analysis was performed when the first 18 (Cohort A1), 12 (Cohort A2), 17 (Cohort B), and 11 (Cohort C) patients in Phase 2 had been treated and followed up for 24&nbsp;weeks. Isa&nbsp;+&nbsp;Cemi demonstrated a manageable safety profile with no new safety signals. No dose-limiting toxicities were observed at the starting dose; thus, the starting dose of each drug was confirmed as the RP2D. Based on the Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of patients achieved a complete or partial response. Pharmacokinetic analyses suggested no effect of Cemi on Isa exposure. Modest clinical efficacy was observed in patients with cHL regardless of prior anti-PD-1/PD-L1 exposure. In DLBCL or PTCL cohorts, interim efficacy analysis results did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Isa&nbsp;+&nbsp;Cemi did not have a synergistic effect in these patient populations

Integrative analysis of a phase 2 trial combining lenalidomide with CHOP in angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) is a frequent T-cell lymphoma in the elderly population that has a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy. Lenalidomide, which has been safely combined with CHOP to treat B-cell lymphoma, has shown efficacy as a single agent in AITL treatment. We performed a multicentric phase 2 trial combining 25 mg lenalidomide daily for 14 days per cycle with 8 cycles of CHOP21 in previously untreated AITL patients aged 60 to 80 years. The primary objective was the complete metabolic response (CMR) rate at the end of treatment. Seventy-eight of the 80 patients enrolled were included in the efficacy and safety analysis. CMR was achieved in 32 (41%; 95% confidence interval [CI], 30%-52.7%) patients, which was below the prespecified CMR rate of 55% defined as success in the study. The 2-year progression-free survival (PFS) was 42.1% (95% CI, 30.9%-52.8%), and the 2-year overall survival was 59.2% (95% CI, 47.3%-69.3%). The most common toxicities were hematologic and led to treatment discontinuation in 15% of patients. This large prospective and uniform series of AITL treatment data was used to perform an integrative analysis of clinical, pathologic, biologic, and molecular data. TET2, RHOA, DNMT3A, and IDH2 mutations were present in 78%, 54%, 32%, and 22% of patients, respectively. IDH2 mutations were associated with distinct pathologic and clinical features and DNMT3A was associated with shorter PFS. In conclusion, the combination of lenalidomide and CHOP did not improve the CMR in AITL patients. This trial clarified the clinical impact of recurrent mutations in AITL. This trial was registered at www.clincialtrials.gov as #NCT01553786