Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues.

Although biliary tract cancers are traditionally considered rare in Western countries, their incidence and mortality rates are rising worldwide. A better knowledge of the genomic landscape of these tumor types has broadened the number of molecular targeted therapies, including angiogenesis inhibitors. The role of immune checkpoint inhibitors (ICIs) could potentially change the first-line therapeutic approach, but monotherapy with ICIs has shown disappointing results in CCA. Several clinical trials are evaluating combination strategies that include immunotherapy together with other anticancer agents with a synergistic activity. The tumor microenvironment (TME) composition plays a pivotal role in the prognosis of BTC patients. The accumulation of immunosuppressive cell types, such as tumor-associated macrophages (TAMs) and regulatory T-cells, together with the poor infiltration of cytotoxic CD8+ T-cells, is known to predispose to a poor prognosis owing to the establishment of resistance mechanisms. Likewise, angiogenesis is recognized as a major player in modulating the TME in an immunosuppressive manner. This is the mechanistic rationale for combination treatment schemes blocking both immunity and angiogenesis. In this scenario, this review aims to provide an overview of the most recent completed or ongoing clinical trials combining immunotherapy and angiogenesis inhibitors with/without a chemotherapy backbone.

History of Extensive Disease Small Cell Lung Cancer Treatment: Time to Raise the Bar? A Review of the Literature.

Several trials have tried for decades to improve the outcome of extensive disease small cell lung cancer (ED-SCLC) through attempts to modify the standard treatments. Nevertheless, platinum/etoposide combination and topotecan have remained respectively the first and the second line standard treatments for the last 40 years. With the advent of immunotherapy, this scenario has finally changed. Our review aims to provide an overview of the primary studies on the actual therapeutic strategies available for ED-SCLC patients, and to highlight emerging evidence supporting the use of immunotherapy in SCLC patients.

Effectiveness of screening and treatment of children with severe acute malnutrition by community health workers in Simiyu region, Tanzania: a quasi-experimental pilot study.

Health system constraints hamper treatment of children with severe acute malnutrition (SAM) in Tanzania. This non-inferiority quasi-experimental study in Bariadi (intervention) and Maswa (control) districts assessed the effectiveness, coverage, and cost-effectiveness of SAM treatment by community health workers (CHWs) compared with outpatient therapeutic care (OTC). We included 154 and 210 children aged 6-59 months with SAM [mid-upper arm circumference (MUAC) < 11.5 cm] without medical complications in the control and intervention districts, respectively. The primary treatment outcome was cure (MUAC ≥ 12.5 cm). We performed costing analysis from the provider's perspective. The probability of cure was higher in the intervention group (90.5%) than in the control group (75.3%); risk ratio (RR) 1.17; 95% CI 1.05, 1.31 and risk difference (RD) 0.13; 95% CI 0.04, 0.23. SAM treatment coverage was higher in the intervention area (80.9%) than in the control area (41.7%). The cost per child treated was US$146.50 in the intervention group and US$161.62 in the control group and that per child cured was US$161.77 and US$215.49 in the intervention and control groups, respectively. The additional costs per an additional child treated and cured were US$134.40 and US$130.92, respectively. Compared with OTC, treatment of children with uncomplicated SAM by CHWs was effective, increased treatment coverage and was cost-effective.

Next Generation Sequencing in Non-Small Cell Lung Cancer: Pitfalls and Opportunities.

Lung cancer remains the first cause of cancer-related deaths worldwide. Thanks to the improvement in the knowledge of the biology of non-small cell lung cancer (NSCLC), patients' survival has significantly improved. A growing number of targetable molecular alterations have been identified. Next-generation sequencing (NGS) has become one of the methodologies entered in clinical practice and was recently recommended by the European society for medical oncology (ESMO) to perform a comprehensive molecular characterization in patients with cancer. The current review provides an overview of the clinical trials that have explored the impact of NGS in patients with cancer, its limits, and advantages.

Evaluation of tuberculosis cases occurring in ten outlying cities and reported in the Entorno region of the state of Goiás and reported in the neighboring Federal District: analysis of the incidence of tuberculosis in those cites.

OBJECTIVE: To evaluate tuberculosis cases occurring in the greater metropolitan area of the Distrito Federal (MADF, encompassing the Federal District, i.e., the national capital of Brasília, located in the state of Goiás) but reported in Brasília itself and to analyze the influence that this has on the effectiveness of the tuberculosis control program, as well as on the collection of socioeconomic and demographic data related to tuberculosis incidence rates. METHODS: Rates of tuberculosis incidence, cure, noncompliance, treatment failure, mortality, and referral, as well as socioeconomic and demographic data, were reviewed for patients from ten MADF cities. RESULTS: From 2000 to 2004, 714 new cases of tuberculosis were reported in the cities studied, 436 (61%) of which were treated in Brasília and were therefore not included in the Goiás database. Among patients treated only in the MADF cities studied, the mean incidence of tuberculosis ranged from 4.40 to 10.02/100,000 inhabitants. When those treated in Brasília were included, the incidence significantly increased, ranging from 15.16 to 20.54/100,000 inhabitants (p < 0.001). The rate at which contacts of tuberculosis patients were investigated was low, and treatment outcomes were unsatisfactory in the MADF cities studied and in Brasília. Socioeconomic and demographic data were consistent with the tuberculosis incidence. CONCLUSION: The number of tuberculosis patients treated in the city in which they resided was lower than expected. Treatment in another city might impair tuberculosis control. The recalculated tuberculosis incidence is consistent with the socioeconomic and demographic profile of the region. A federal surveillance system could be efficiently optimized, improving the control of this disease.

Avaliação da notificação no Distrito Federal de casos de tuberculose residentes em dez municípios goianos do entorno e análise da incidência de tuberculose nestas localidades / Evaluation of tuberculosis cases occurring in ten outlying cities and reported in the Entorno region of the state of Goiás and reported in the neighboring Federal District: analysis of the incidence of tuberculosis in those cites

OBJETIVO: Avaliar a notificação, no Distrito Federal (DF), de casos de tuberculose em residentes nos municípios goianos da região do Entorno e possíveis influências no Plano de Controle da Tuberculose; analisar a taxa de incidência da tuberculose nos municípios e a interferência da situação socioeconômica e das características demográficas sobre esta taxa. MÉTODO: Analisaram-se dados relativos à incidência de tuberculose, taxas de cura, abandono, falência de tratamento, óbito, transferência e informações socioeconômicas e demográficas de dez municípios goianos. RESULTADOS: No período de 2000 a 2004, foram notificados 714 casos novos de tuberculose em residentes nos municípios estudados, sendo que 436 (61,0 por cento) foram atendidos no DF, não sendo registrados no Sistema de Informação de Goiás. Considerando-se os casos atendidos somente em Goiás, a média de incidência de tuberculose do grupo variou de 4,40 a 10,02/100.000 habitantes; somando-se os atendidos no DF, a incidência aumentou significativamente, variando de 15,16 a 20,54/100.000 habitantes (p < 0,001). A taxa de contatos examinados foi baixa e os resultados de tratamento insatisfatórios, tanto em Goiás como no DF. Os dados socioeconômicos e demográficos foram compatíveis com as taxas de incidência. CONCLUSÃO: O número de casos de tuberculose atendidos pelos próprios municípios foi abaixo do esperado e o atendimento fora do município de residência pode comprometer o controle da tuberculose. A incidência de tuberculose recalculada é compatível com o perfil socioeconômico e demográfico da região. Um sistema de vigilância com base territorial pode ter sua eficiência otimizada, melhor contribuindo para o controle da enfermidade.

OBJECTIVE: To evaluate tuberculosis cases occurring in the greater metropolitan area of the Distrito Federal (MADF, encompassing the Federal District, i.e., the national capital of Brasília, located in the state of Goiás) but reported in Brasília itself and to analyze the influence that this has on the effectiveness of the tuberculosis control program, as well as on the collection of socioeconomic and demographic data related to tuberculosis incidence rates. METHODS: Rates of tuberculosis incidence, cure, noncompliance, treatment failure, mortality, and referral, as well as socioeconomic and demographic data, were reviewed for patients from ten MADF cities. RESULTS: From 2000 to 2004, 714 new cases of tuberculosis were reported in the cities studied, 436 (61 percent) of which were treated in Brasília and were therefore not included in the Goiás database. Among patients treated only in the MADF cities studied, the mean incidence of tuberculosis ranged from 4.40 to 10.02/100,000 inhabitants. When those treated in Brasília were included, the incidence significantly increased, ranging from 15.16 to 20.54/100,000 inhabitants (p < 0.001). The rate at which contacts of tuberculosis patients were investigated was low, and treatment outcomes were unsatisfactory in the MADF cities studied and in Brasília. Socioeconomic and demographic data were consistent with the tuberculosis incidence. CONCLUSION: The number of tuberculosis patients treated in the city in which they resided was lower than expected. Treatment in another city might impair tuberculosis control. The recalculated tuberculosis incidence is consistent with the socioeconomic and demographic profile of the region. A federal surveillance system could be efficiently optimized, improving the control of this disease.

Capacitação em tuberculose. Experiência do serviço público de Saúde em Goiás

Introdução: A capacitação de profissionais de saúde no âmbito da Saúde Pública é uma das ações importantes para o controle da tuberculose. Objetivo: Relatar uma experiência inter-institucional entre a Secretaria Estadual de Saúde de Goiás, a Secretária Municipal de Saúde de Goiânia, a Universidade Federal de Goiás e a Fundação Belga Damien, com capacitação em tuberculose para profissionais da rede pública durante os anos de 2003, 2004 e 2005. Método: Foram realizados cursos com conteúdo e métodos pedagógicos padronizados e os resultados foram avaliados por meio de testes de conhecimento feitos no início e após o término dos cursos. Resultados: A avaliação dos alunos em relação aos cursos foi positiva. O número de acertos no teste de conhecimentos inicial foi maior entre médicos que entre enfermeiros. Houve avanço no aprendizado da tuberculose tanto para profissionais do nível médio quanto do superior, na capital e interior. Esta evolução foi menor, porém significativa, para alunos dos cursos de nível médio. Conclusão: A experiência foi positiva do ponto de vista pedagógico. Considerou-se o conteúdo objetivo e qualitativamente adequado e a metodologia atrativa