Bariatric surgery in women in reproductive age: recommendations from the “Diabetes and Pregnancy” and “Diabetes and Obesity” working committees from the Argentine Society of Diabetes

El incremento de la obesidad en el mundo, a edades más tempranas, ha tenido un impacto negativo especialmente en las mujeres en edad reproductiva. Se ven afectadas tanto la fertilidad como la tasa de embarazos de riesgo, de niños con bajo peso al nacer, pretérmino e índice de cesáreas. La cirugía bariátrica como alternativa de tratamiento de la obesidad ha mejorado la fertilidad, pero el trastorno malabsortivo que provoca modifica la absorción de nutrientes en la madre y en el feto. El diagnóstico de diabetes gestacional se dificulta dado que la prueba de tolerancia oral a la glucosa estaría contraindicada en estos casos. El objetivo de estas recomendaciones es proveer herramientas para el control y seguimiento de mujeres en edad reproductiva sometidas a cirugía bariátrica.Worldwide increased obesity prevalence at early ages particularly affects women of reproductive ages. Both fertility and risk pregnancy rates are affected, of low birth weight infants, prematures and cesarean section rates have been modified considerably. Bariatric surgery is a validated tool to improve fertility but nutrient malabsorption as a consequence of surgery could affect mother and fetus nutrition and development. Gestational diabetes diagnosis turns difficult in this group of obese patients after bariatric surgery since oral glucose tolerance testing would be contraindicated in these cases. The aim of these recommendations was to offer tools for a good control and follow up of women at reproductive age.Fil: Gutt, Susana. Hospital Italiano de Buenos Aires; ArgentinaFil: Rovira, Gabriela. Universidad de Buenos Aires. Facultad de Medicina. Sede Hospital Britanico Bs.as; ArgentinaFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Espinoza, Frank. Instituto Cardiovascular Lezica; ArgentinaFil: Mociulsky, Juliana. Clínica de Nutrición y Salud Dr. Cormillot; ArgentinaFil: Sucani, Stella. Provincia de Misiones. Hospital Escuela de Agudos Dr. Ramon Madariaga; ArgentinaFil: Kojdamanian, Verónica. Centro de Educación, Prevención y Asistencia al paciente diabético; ArgentinaFil: Aguirre Ackermann, Marianela. Centro Integral de Endocrinología y Nutrición; ArgentinaFil: Álvarez, María Graciela. Centro de Estudio y Tratamiento de la Obesidad Severa; ArgentinaFil: Camaño, Alejandro. Centro Médico de Especialidades y Diagnósticos Privado para la Salud; ArgentinaFil: Glatstein, Liliana. Centro Médico San Andrés; ArgentinaFil: Lifszyc, Paula. Hospital Carlos G. Durand; ArgentinaFil: Gómez Martin, Carolina. Centro Integral de Endocrinología y Diabetes; ArgentinaFil: Mendes, Patricio. Maternidad San Lucas; ArgentinaFil: Menéndez, Estrella. Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno; ArgentinaFil: Yuma, María. Hospital Italiano de Buenos Aires; ArgentinaFil: Bertona, Celina. Universidad Nacional de Cuyo; ArgentinaFil: Cafaro, Lilia. Obesidad y Cirugía Mini Invasiva; ArgentinaFil: Fuentes, Susana. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad En Red El Cruce Dr. Nestor Carlos Kirchner Samic; ArgentinaFil: Salzberg, Susana. Instituto Centenario; ArgentinaFil: Basualdo, Natalia. Hospital Materno Infantil Ramón Sardá; ArgentinaFil: González, Sandra . Cínica IMA; ArgentinaFil: Villarroel Parra, Beatriz. Hospital de Agudos Dalmacio Vélez Sarsfield; Argentina. Sanatorio Santa Isabel; ArgentinaFil: Musso, Carla. Fundacion Favaloro; Argentin

A real-world retrospective, observational study of first-line pembrolizumab plus chemotherapy for metastatic non-squamous non-small cell lung cancer with PD-L1 tumor proportion score < 50% (PEMBROREAL)

IntroductionThe phase III Keynote-189 trial established a first-line treatment combining pembrolizumab with pemetrexed and platinum as a standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) without known EGFR and ALK driver mutations and independent of programmed cell death ligand 1 (PD-L1) expression. However, in Italy, eligibility for the National Health Service payment program is limited to patients with PD-L1 &lt;50%. The PEMBROREAL study assesses the real-world effectiveness and safety of pembrolizumab in patients eligible for the National Health Service payment program.MethodsPEMBROREAL is a retrospective, observational study on patients with NSCLC who started pembrolizumab combined with pemetrexed and platinum within the reimbursability time window, considered as December 2019 to December 2020. The primary endpoints were to assess progression-free survival (PFS) and overall survival (OS; using the Kaplan–Meier method), response to therapy, and tolerability.ResultsUntil February 2022, 279 patients (median follow-up: 19.7 months) have been observed. The median PFS was 8.0 months (95% confidence interval: 6.5–9.2). OS was not reached, but we can estimate a 12- to 24-month survival rate for the combined treatment: 66.1% and 52.5%, respectively. PD-L1 expression and Eastern Cooperative Group (ECOG) Performance Status were both associated with PFS and OS. Overall, only 44.4% of patients reported an adverse event, whereas toxicity led to a 5.4% discontinuation rate.ConclusionThe results of the PEMBROREAL study have shown that the combined treatment of pembrolizumab with pemetrexed and platinum is effective for metastatic non-squamous NSCLC, even for patients with PD-L1 levels below 50%, despite the differences in patient demographics and pathological features compared to the Keynote-189 study. The adverse events reported during the study were more typical of chemotherapy treatment rather than immunotherapy, and physicians were able to manage them easily

Consenso intersocietario para el tratamiento de la obesidad en adultos en Argentina

La obesidad es una enfermedad crónica que genera altos costos en salud, cuyo tratamiento, en ocasiones, no se aborda o se lo hace de forma inadecuada, y muchas veces no se basa en la evidencia disponible. Es por ello que, a partir de una iniciativa de la Sociedad Argentina de Nutrición, diferentes sociedades científicas se reunieron con el objetivo de construir un documento actualizado, basado en una metodología científica, que aporte al mejor tratamiento de las personas que viven con obesidad en Argentina. Este es el primer Consenso Intersocietario para el tratamiento de la Obesidad en adultos en Argentina a partir del cual se obtuvieron recomendaciones para la práctica clínica basadas en la evidencia científica. Es una necesidad primordial contar con herramientas, adecuadas a la realidad local y consensuadas por expertos de distintas disciplinas

HIV-1 Tat protein vaccination in mice infected with Mycobacterium tuberculosis is safe, immunogenic and reduces bacterial lung pathology

The therapeutic HIV-1 Tat protein vaccine is in advanced clinical development. Tuberculosis, the main AIDS co-infection, is highly endemic in areas where AIDS prevention through vaccination is needed. However, safety and immunogenicity of Tat vaccination in the course of Mycobacterium tuberculosis (Mtb) infection is still unknown and it prevents the possibility to administer the vaccine to Mtb-infected individuals. We addressed the interplay and effects of Tat vaccination on Mtb infection in immunocompetent mice

Metabolism and molecular systems for the biotransformation of aromatic molecules. Annual Project Meeting: Naples, 19 January 2010

The collection of papers is the result of the first year's results of the Project: METABOLISM AND MOLECULAR SYSTEMS FOR THE BIOTRANSFORMATION OF AROMATIC MOLECULES. Aim of the research project is to gain knowledge in microorganisms endowed with the ability of transforming aromatic compounds, and in the genes and enzymes involved in this process. Particular attention is paid to the information acquired for its use in the development of biosynthetic systems for bioremediation and bioconversions. The pathways responsible for the aerobic catabolism of aromatic molecules are generally made up of an upper pathway, where hydroxylation reactions leading to the formation of hydroxylated intermediates occur, and a lower pathway where the aromatic ring of these dihydroxylated molecules are cleaved, and eventually converted, after several enzymatic steps, into intermediates of the Krebs cycle. It goes without saying that the great potential of these systems is related to the acquisition of information about the enzymatic systems involved and the regulation of their corresponding genes. The utilization of these micro-organisms can be expanded and improved by: (i) characterizing new microorganisms and their enzymatic systems to sort out a wide panel of enzymatic systems endowed with different metabolic abilities and different specificity, (ii) elucidating the transcriptional regulation and the molecular determinants responsible for the enzymatic activities in systems that are already known and in those that will be available during the development of the project. Moreover, in order to evaluate the influence of the information gained in developing processes it will be necessary to (iii) validate the development of a small number of applications. More specifically these goals have been achieved through: 1) Isolation and characterization of new bacterial strains either by isolation from polluted sites or by spotting new ones through the analysis of annotated genomes for identifying both new microorganisms and new enzymatic activities with enhanced catalytic biodegradative properties; 2) identification and analysis of the molecular determinants of the specificity of enzymatic systems either already available or new ones which will be available during the development of the project; 3) investigation of the transcription regulative systems involved in the expression of the enzymatic systems (in particular key enzymes in the metabolism of aromatic compounds) in both psychrophilic and mesophilic bacteria; 4) utilization of the results obtained from the different approaches above to set-up new biocatalysts for the bioremediation of model wastewaters and for the biosynthesis of compounds of pharmaceutical and industrial interest

Effect of the redox state on HIV-1 tat protein multimerization and cell internalization and trafficking

The redox state of the cysteine-rich region of the HIV Tat protein is known to play a crucial role in Tat biological activity. In this article, we show that Tat displays two alternative functional states depending on the presence of either one or three reduced sulphydryl groups in the cysteine-rich region, respectively. Using different approaches, a disulfide pattern has been defined for the Tat protein and a specific DTT-dependent breaking order of disulfide bonds highlighted. The Tat redox state deeply influences macrophage protein uptake. Immunoistochemistry analysis shows that the oxidized protein does not enter cells, whereas partially reduced protein reaches the cytosol and, to a limited extent, the nucleus. Finally electrophoretic analysis shows Tat high-molecular weight multi-aggregation, resulting in the loss of biological activity. This is due to strong electrostatic and metal-binding interactions, whereas Tat dimerization involves metal-binding interactions as well as disulfide bond formation