A comprehensive supportive care program for fine-tuning cancer immunotherapy.

Supportive care has become a new pilar of modern oncology, and a great deal of research is being conducted in that area, especially on immune checkpoint inhibitors (ICIs), to help fine-tune immunotherapy. Four major areas of supportive care can enhance responsiveness to cancer immunotherapy whilst minimizing adverse effects: diet (indirectly, by modulating the microbiota or directly, by modulating the immune system), physical activity (by modulating the immune system), electronic patient-reported outcomes (ePRO) (by detecting and treating immune-related adverse events early on), and co-medication management (to possibly suppress those drugs that negatively affect the efficacy of ICIs). Therefore, patients treated with ICIs could receive a systematic multimodal supportive care program encompassing regular nutritional counseling, regular physical activity under the supervision of a physical activity professional, ePRO follow-up, and regular pharmaceutical counseling. This type of approach needs to be evaluated in well-conducted randomized clinical trials.

Torque resistance of impression copings after direct implant impression: An in vitro evaluation of impression materials with and without adhesive.

STATEMENT OF PROBLEM: No data are available on the ability of an impression coping to resist the manual placement of an abutment replica (implant analog) during prosthodontic laboratory procedures after a direct (pick-up) impression. PURPOSE: The purpose of this in vitro study was to evaluate the torque resistance of impression copings after a direct impression, that is, the amount of rotational torque sufficient to induce irreversible displacement of impression copings in the impression material bulk once the impression has been made. MATERIAL AND METHODS: A reference model with 5 abutment replicas was constructed. Five impression copings were screwed onto the abutment replicas, and standardized impressions were made. A controlled twisting force was applied to each impression coping. A torque tester recorded the torque variation. Three elastomeric impression materials were tested. ANOVA and the Tukey test (α=.05) were performed using an average of 30 measurements per impression material, with and without adhesive. RESULTS: ANOVA and the Tukey test results showed that the adhesive, cohesive, and mechanical bonds between the impression coping and the impression material depended greatly on the type of material and that the average rupture threshold of these bonds was statistically significantly different in pairwise comparisons (P<.05). The curve analysis showed that when the impression materials are used with adhesives, the deformation of the interface is irreversible beyond 5 Ncm of torque. CONCLUSIONS: The polyether impression material is the direct impression material that showed the highest breakdown threshold for adhesive bonding when used without an adhesive. The use of an adhesive on impression copings leads to irreversible deformation of the interface at torque stresses well below the adhesive bond threshold of the same materials used without an adhesive.

[Combination strategies for checkpoint inhibition: Current practices and perspectives]. / Combinaisons d'inhibiteurs de points de contrôle immunitaires en oncologie : état de l'art et perspectives.

T-cell checkpoint blockade therapies have revolutionized treatment protocols and prognosis in patients with cancer. Pointed out by the success of PD-1 (programmed cell death-1) plus CTLA-4 (cytotoxic-T-lymphocyte associated antigen 4) blockade in patients with melanoma, the perspective of new synergistic immunotherapy combinations seems to be an important opportunity to improve outcomes for patients. In this article, we first focus on immunotherapy combinations that have shown their efficiency and that are currently approved in solid tumors. Then, we present a summary of emerging targets with reported pre-clinical efficacy and currently evaluated through ongoing clinical trials and other immunomodulatory molecules in the tumor microenvironment.

Temporal trend of mortality from infectious respiratory diseases in childhood in Minas Gerais, Brazil, 2000-2020.

MAIN RESULTS: From 2000 to 2020, there was a downward trend in mortality due to infectious respiratory disease in children living in Minas Gerais - even in 2020, the year of the COVID-19 pandemic. IMPLICATIONS FOR SERVICES: There was a reduction in child deaths due to respiratory infections; health services should be alerted as to the considerable presence of ill-defined or inconclusive codes (garbage codes) on death certificates. PERSPECTIVES: It is necessary to maintain the effectiveness of health actions among the mother and child population and to improve the records held on the Mortality Information System, in order to enable better monitoring of mortality as well as to enable analytical studies to be conducted. OBJECTIVE: to analyze temporal trends in mortality due to infectious respiratory disease in children under 12 years old in Minas Gerais, Brazil, from 2000 to 2020. METHODS: this was an ecological study using data on infectious respiratory disease in children under 12 years old registered on the Mortality Information System; the variables studied were etiological agent, anatomical site of infection and sex; trends were analyzed by joinpoint regression. RESULTS: of the 4,688 registered deaths, the etiological agent of the disease was unspecified for 84.5% of them, and 88% were due to lower respiratory tract infections; there was a decreasing trend in deaths and in the proportion of deaths due to unspecified etiologic agents; in 2020, there was an increase in deaths with viral etiology and systemic involvement. CONCLUSION: in addition to the change in the etiologic profile, there was a reduction in mortality due to infectious respiratory diseases in children, even considering 2020, the year of the COVID-19 pandemic.

Impact of Androgen Deprivation Therapy Associated to Conformal Radiotherapy in the Treatment of D'Amico Intermediate-/High-Risk Prostate Cancer in Older Patients.

PURPOSE/OBJECTIVE: The association of 3D Conformal External Beam Radiotherapy (3D-CEBRT) with adjuvant Androgen Deprivation Therapy (ADT) proved to treat patients with intermediate- and high-risk localized prostate cancer (IR and HR). However, older patients were underrepresented in literature. We aimed to report the oncological results and morbidity 3D-CEBRT +ADT in ≥80 years patients. MATERIAL AND METHODS: From June 1998 to July 2017, 101 patients ≥80 years were included in a tertiary center. The median age was 82 years. ADT was initiated 3 months prior 3D-CEBRT in all patients, with a total duration of 6 months for IR prostate cancer (group A; n = 41) and 15 months for HR prostate cancer (group B; n = 60). Endpoints included overall survival (OS), metastasis-free survival (DMFS), biochemical recurrence-free survival (BRFS) and toxicity. RESULTS: Five years-OS was 95% and 86.7% in groups A and B, respectively. Cardiovascular events occurred in 22.8% of ≥80 years patients with no impact on OS. In the multivariate analysis, age <82 years, Karnofsky index and normalization of testosterone levels were significantly associated with better OS. CONCLUSION: Age ≥80 years should not be a limitation for the treatment of IR and HR prostate cancer patients with 3D-CEBRT and ADT, but cardiovascular monitoring and prevention are mandatory.

Targeting BRCA Deficiency in Breast Cancer: What are the Clinical Evidences and the Next Perspectives?

Breast cancers (BC) associated with germline mutations of BRCA1/2 represent 3⁻5% of cases. BRCA1/2-associated BC have biological features leading to genomic instability and potential sensitivity to DNA damaging agents, including poly(ADP-ribose) polymerase (PARP) and platinum agents. In this review, we will summarize clinical trials of chemotherapy and PARP inhibitors (PARPi), alone or in combination, at the early or late stage of BRCA1/2-associated BC. We will also present the mechanisms of resistance to PARPi as well as the new therapeutic strategies of association with PARPi. Finally, we will discuss under which conditions the use of DNA damaging agents can be extended to the BRCA1/2-wild type population, the BRCAness concept.

Nivolumab in routine practice for older patients with advanced or metastatic non-small cell lung cancer.

BACKGROUND: Nivolumab is approved worldwide as second-line treatment for metastatic non-small cell lung cancer (NSCLC). Despite the fact that most of these cancers are being diagnosed in the older patients, few of the patients were included in pivotal trials. We aimed to describe efficacy and safety in a "real-world" older population. PATIENTS AND METHODS: We retrospectively collected data from older patients (≥70 years old) with advanced or metastatic NSCLC treated with Nivolumab in our institution. We analyzed safety (CTCAE v4.0 criteria), efficacy (clinical benefit rate, progression-free survival, and overall survival), and correlated these features to geriatric parameters and PD-L1 expression. Along with this cohort, we assessed safety at a national level by retrieving all cases of Nivolumab (prescribed for NSCLC) induced adverse events analyzed by the French pharmacovigilance network during the inclusion period. RESULTS: From July 2015 to September 2016, 30 patients were enrolled with a median age of 75.2. Clinical benefit rate was 30.6%. Median progression-free survival and overall survival were 3.3 and 7.1 months, respectively. Fifteen patients (50%) presented an immune-related adverse event (IrAE) of any grade, including four high grade IrAEs. Two hundred and eighty IrAEs had been notified to the French pharmacovigilance network including 91 (35.2%) concerning older patients. Frequency and pattern of IrAEs were similar for older patients and younger subjects. CONCLUSIONS: Even though frequency and patterns of IrAEs are different from pivotal studies, these results don't seem specific to older patients. Further prospective investigations are needed to better characterize and predict the impact of Nivolumab on older patients with NSCLC.

Morbimortalidade por zoonoses de acometimento respiratório em Minas Gerais: um estudo epidemiológico descritivo / Morbimortality due to respiratory affecting zoonoses in Minas Gerais: a descriptive epidemiological study

Objetivo: descrever os registros de óbitos e hospitalizações por zoonoses respiratórias em residentes de Minas Gerais, de 2000 a 2020. Métodos: utilizou-se abordagem quantitativa descritiva com dados secundários não nominais da Secretaria Estadual de Saúde do estado. Os dados referem-se a 2000 a 2020 e foram retirados do SIM e SIH, sendo analisados sob a estatística descritiva. Resultados: registraram-se 46.178 hospitalizações e 13.317 óbitos, sendo os vírus os principais agentes nas taxas de internação e mortalidade, com pico em 2020. Entre 2000 e 2019, as internações foram predominantes em homens, faixa etária 0-17 anos (42,8%) e raça branca (13,6%), com maior mortalidade na faixa 45-59 anos (34,7%) e raça branca (54,0%). Em 2020, ambas predominaram em homens, acima de 60 anos e nas raças branca e parda. Conclusão: os achados contribuem para conhecer a ocorrência das zoonoses na população mineira e subsidiar futuras ações de vigilância e controle dessas doenças.

Objective: to describe the records of deaths and hospitalizations due to respiratory zoonoses in residents of Minas Gerais from 2000 to 2020. Methods: a descriptive quantitative approach was used with non-nominal secondary data from the State Department of Health. Data refers to the years between 2000-2020 and were taken from SIM and SIH, being analyzed under descriptive statistics. Results: there were 46,178 hospitalizations and 13,317 deaths, with viruses being the main agents in hospitalization and mortality rates, with a peak in 2020. Between 2000 and 2019, hospitalizations were predominant in men aged 0-17 years (42.8%) and white race (13.6%), with higher mortality in the 45-59 age group (34.7%) and white race (54.0%). In 2020, both predominated in men over 60 years old, both in white and Hispanic races. Conclusion: the findings explain the occurrence of zoonoses in the population of Minas Gerais and support future surveillance and control actions for these diseases.

Temporal trend of mortality from infectious respiratory diseases in childhood in Minas Gerais, Brazil, 2000-2020 / Tendencia temporal de la mortalidad por enfermedades respiratorias infecciosas en la infancia en Minas Gerais, Brasil, 2000-2020 / Tendência temporal da mortalidade por doenças respiratórias infecciosas na infância, em Minas Gerais, 2000-2020

ABSTRACT Objective: to analyze temporal trends in mortality due to infectious respiratory disease in children under 12 years old in Minas Gerais, Brazil, from 2000 to 2020. Methods: this was an ecological study using data on infectious respiratory disease in children under 12 years old registered on the Mortality Information System; the variables studied were etiological agent, anatomical site of infection and sex; trends were analyzed by joinpoint regression. Results: of the 4,688 registered deaths, the etiological agent of the disease was unspecified for 84.5% of them, and 88% were due to lower respiratory tract infections; there was a decreasing trend in deaths and in the proportion of deaths due to unspecified etiologic agents; in 2020, there was an increase in deaths with viral etiology and systemic involvement. Conclusion: in addition to the change in the etiologic profile, there was a reduction in mortality due to infectious respiratory diseases in children, even considering 2020, the year of the COVID-19 pandemic.

RESUMEN Objetivo: analizar las tendencias temporales de mortalidad por enfermedades respiratorias infecciosas en niños de hasta 12 años incompletos en Minas Gerais, Brasil, de 2000 a 2020. Métodos: estudio ecológico con datos de muertes en niños de hasta 12 años incompletos, registradas en el Sistema de Información de Mortalidad; las variables estudiadas fueron: agente etiológico, sitio anatómico de infección y género; las tendencias se analizaron mediante la regresión jointpoint. Resultados: de las 4.688 muertes registradas, el 84,5% tenía un agente etiológico de la enfermedad no especificado y el 88% se debía a infecciones de las vías respiratorias bajas; hubo una tendencia decreciente en las muertes y en la proporción de muertes por agente no especificado; en 2020, hubo un aumento en el número de muertes de etiología viral y acometimiento sistémico. Conclusión: además del cambio en el perfil etiológico, hubo una reducción de la mortalidad por enfermedades respiratorias infecciosas en niños, incluso considerando 2020, año de la pandemia de Covid-19.

RESUMO Objetivo: analisar as tendências temporais de mortalidade por doença respiratória infecciosa em crianças com até 12 anos incompletos, Minas Gerais, Brasil, de 2000 a 2020. Métodos: estudo ecológico dos óbitos por doença respiratória infecciosa em crianças com até 12 anos incompletos, registrados no Sistema de Informações sobre Mortalidade; as variáveis estudadas foram o agente etiológico, o sítio anatômico da infecção e o sexo; as tendências foram analisadas por regressão joinpoint. Resultados: dos 4.688 óbitos registrados, 84,5% tiveram agente etiológico não especificado e 88% decorreram de infecções nas vias aéreas inferiores; observou-se tendência decrescente nos óbitos e na proporção de óbitos provocados por agente etiológico não especificado; em 2020, houve incremento do número de óbitos de etiologia viral e de acometimento sistêmico. Conclusão: além da alteração no perfil etiológico, notou-se redução da mortalidade por doenças respiratórias infecciosas em crianças - mesmo em 2020, ano de pandemia de covid-19.

Epidemiologia da dengue em Minas Gerais de 2009 a 2019: uma análise descritiva / Epidemiology of dengue in Minas Gerais from 2009 to 2019: a descriptive analysis

Introdução: Atualmente, a dengue gera um importante impacto sobre o bem-estar dos pacientes e a economia do sistema público de saúde. Nesse sentido, evidencia-se a necessidade da realização de estudos epidemiológicos de modo a auxiliar nas análises acerca da realidade estadual. Objetivo: Caracterizar o perfil epidemiológico da dengue em Minas Gerais, de 2009 a 2019. Material e Métodos: Estudo observacional de caráter descritivo e quantitativo utilizando dados de notificações e internações obtidos do Sistema de Informação de Agravos de Notificação e do Sistema de Informações Hospitalares, a partir do TABNET. Calcularam-se taxas de letalidade, incidência e internação, utilizando dados demográficos do Departamento de Informática do Sistema Único de Saúde para os cálculos de incidência e internação. As variáveis de estudo foram: ano de ocorrência, macrorregião de residência, faixa etária, evolução e classificação clínica da doença, sexo, escolaridade e raça. Resultados: A dengue possui um caráter cíclico de incidência, e as taxas de letalidade e internação oscilam anualmente. As macrorregiões Centro, Triângulo do Sul, Noroeste, Oeste, Triângulo do Norte e Vale do Aço obtiveram elevadas taxas de incidência, e a macrorregião Leste a maior taxa de internação. A maioria dos casos de dengue foram classificados como "dengue clássica", e a classificação "dengue grave" foi a de menor incidência. Em relação à faixa etária, o intervalo de 15 a 39 anos apresentou maior taxa de incidência e menores taxas de letalidade e de internação, quando comparado à população idosa. Ademais, a evolução a óbito ocorreu mais frequentemente em indivíduos analfabetos. Conclusão: Os achados desse estudo elucidam o perfil epidemiológico da dengue em Minas Gerais, que se caracteriza por apresentar um padrão nacional cíclico de casos, manifestando-se principalmente de forma branda, mas com um acréscimo da morbimortalidade em analfabetos e idosos.

Introduction: Currently, dengue has an important impact on the well-being of patients and the economy of the public health system. In this sense, the need to carry out epidemiological studies is highlighted in order to assist in the analysis of the state's reality. Objective: To characterize the epidemiological profile of dengue in Minas Gerais, from 2009 to 2019. Material and Methods: Observational descriptive and quantitative study based on data on notifications and admissions obtained from the Notifiable Diseases Information System and the Hospital Information System, from TABNET. Rates of lethality, incidence and hospitalization were calculated using demographic data from the information technology department of the Unified Health System to calculate incidence and hospitalization. The study variables were: the year of occurrence, macro-region of residence, age group, evolution and clinical classification of the disease, gender, education and race. Results: Dengue has a cyclical nature of incidence, and lethality and hospitalization rates fluctuate annually. The Central, Southern Triangle, Northwest, West, Northern Triangle and Vale do Aço macro-regions had high incidence rates, and the Eastern macro-region had the highest hospitalization rate. Most dengue cases were classified as 'classic dengue', and the classification 'severe dengue' had the lowest incidence. Regarding the age group, the 15 to 39-year age group had a higher incidence rate and lower mortality and hospitalization rates, when compared to the elderly population. Furthermore, the evolution to death occurred more frequently in illiterate individuals. Conclusion: The findings of this study elucidate the epidemiological profile of dengue in Minas Gerais, which is characterized by presenting a cyclical national pattern of cases, manifesting itself mainly in a mild form, but with an increase in morbidity and mortality in illiterate and elderly people.