Bevacizumab biosimilar and reference bevacizumab in subjects with stage IIIB/IV non-squamous non-small cell lung cancer (STELLA): Design of a confirmatory, double-blind, randomized, controlled study

Background: MB02 is a bevacizumab biosimilar developed to stringent guidelines, including non-clinical and preclinical investigations and a clinical trial as first-line treatment in metastatic colorectal cancer (Romera A et al. Lancet Gastroenterol Hepatol 2018;3 (12): 845-855). A clinical trial (STELLA) has been initiated to confirm there are no clinically meaningful differences between MB02 and reference bevacizumab (Avastin) in terms of efficacy, safety, and immunogenicity (NCT03296163). Methods: STELLA study is a multinational, double-blind, randomized, parallel-group, equivalence study comparing the efficacy and safety of MB02 vs reference bevacizumab plus chemotherapy in subjects with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC)

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Desenvolvimento da inteligência linguística com base na concepção triádica do cérebro

The pedagogical research "Development of linguistic intelligence based on the triadic conception of the brain" was carried out for several years and its population and sample was the educational community of the "Concentración Escolar el Poblado de Girón", grade 5-B of the morning session. This research took as its theoretical basis the authors Waldemar de Gregori with the "Triadic conception of the brain" and Howard Gardner with "The theory of multiple intelligences".Durante varios años se realizó la investigación pedagógica "Desarrollo de la inteligencia linguistica a partir de la concepción trádica del cerebro" cuya población y muestra fue la comunidad educativa de la Concentración Escolar el Poblado de Girón, grado 5-B de la jornnada de la mañana. Esta investigación tomó como base teórica a los autores Waldemar de Gregori con la "Concepción triádica del cerebro" y a Howard Gardner con "La teoría de las inteligencias múltiples".La recherche pédagogique "Développement de l\u27intelligence linguistique basé sur la conception triadique du cerveau" a été menée pendant plusieurs années avec la population et l\u27échantillon de la communauté éducative de la Concentración Escolar el Poblado de Girón, classe 5-B dans la session du matin. Cette recherche a pris pour base théorique les auteurs Waldemar de Gregori avec la "Conception triadique du cerveau" et Howard Gardner avec "La théorie des intelligences multiples".A pesquisa pedagógica "Desenvolvimento da inteligência lingüística com base na concepção triádica do cérebro" foi realizada durante vários anos com a população e a amostra da comunidade educacional da Concentración Escolar el Poblado de Girón, 5ª série B, no período da manhã. Essa pesquisa teve como base teórica os autores Waldemar de Gregori com a "Concepção triádica do cérebro" e Howard Gardner com "A teoria das inteligências múltiplas"

Systemic Bevacizumab for Treatment of Respiratory Papillomatosis: International Consensus Statement

Objectives/Hypothesis: The purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality. Study Design: Delphi method-based survey series. Methods: A multidisciplinary, multi-institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work-up. Results: The international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18). Conclusion: This consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best-practice applications of systemic bevacizumab for patients with early-onset or less-severe disease phenotypes. Level of Evidence: 5 Laryngoscope, 131:E1941–E1949, 2021

Systemic Bevacizumab for Treatment of Respiratory Papillomatosis: International Consensus Statement

Objectives/Hypothesis: The purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality. Study Design: Delphi method-based survey series. Methods: A multidisciplinary, multi-institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work-up. Results: The international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18). Conclusion: This consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best-practice applications of systemic bevacizumab for patients with early-onset or less-severe disease phenotypes. Level of Evidence: 5 Laryngoscope, 131:E1941–E1949, 2021