MET alterations in advanced non-small cell lung cancer.

Precision medicine has helped identify several tumor molecular aberrations to be treated with targeted therapies. These therapies showed substantial improvement in efficacy without excessive toxicity in patients with specific oncogenic drivers with advanced cancers. In metastatic lung cancers, the implementation of broad platforms for molecular tumor sequencing has helped oncology providers identify oncogenic drivers linked with better outcomes when treated upfront with targeted therapies. Mesenchymal-epithelial transition factor (MET) alterations are present in up to 60% of non-small cell lung cancer and are associated with a poor prognosis. Capmatinib and tepotinib are currently the only two approved targeted therapies by the U.S. Food and Drug Administration (FDA) for patients with MET exon 14 skipping mutation. Several agents are being developed to tackle an unmet need in patients with MET alterations. Some of these agents are being used in combination with EGFR targeted therapy to mitigate resistance to EGFR inhibitor. These agents are poised to provide new hope for these patients.

Risk factors for mortality in patients with dengue: A systematic review and meta-analysis.

OBJECTIVE: To investigate risk factors for mortality in dengue. METHODS: We performed a systematic review and meta-analysis searching MEDLINE, Embase, SciELO, LILACS Bireme, and OpenGrey databases to identify eligible observational studies of patients with dengue, of both genders, aged 14 years or older, that analysed risk factors associated with mortality and reported adjusted risk measures with their respective confidence intervals (CIs). We estimated the pooled weighted mean difference and 95% CIs with a DerSimonian and Laird random-effects model. We assessed the methodological quality using the Newcastle-Ottawa Scale. RESULTS: Of 1,170 citations reviewed, 18 papers, with a total of 25,851 patients, were included in the systematic review and 12 in the meta-analysis. Severe hepatitis (OR 29.222, 95% CI 3.876-220.314), dengue shock syndrome (OR 23.575, 95% CI 3.664-151.702), altered mental status (OR 3.76, 95% CI 1.67-8.42), diabetes mellitus (OR 3.698, 95% CI 1.196-11.433), and higher pulse rate (OR 1.039, 95% CI 1.011-1.067) are associated with mortality in patients with dengue. All studies included were classified as having a high quality. CONCLUSIONS: Proper identification and management of these risk factors should be considered to improve patient outcomes and reduce the hidden burden of this neglected tropical disease. Future well-designed studies are needed to investigate the association of other clinical, radiological, and laboratorial findings with mortality in dengue, as well as to develop prognostic models based on the risk factors found in our study.

COVID-19 and Kidney: a narrative review / COVID-19 e os rins: uma revisão narrativa

Abstract COVID-19 is a pandemic associated with systemic clinical manifestations. In this study, we aimed to present a narrative review on kidney involvement in COVID-19. Kidney involvement could be derived from direct cytopathic effects, immunological mechanisms, indirect effects on renal tissue through other mediators, and dysfunction or injury of other organs. The evolution of COVID-19 may be complicated with acute kidney injury (AKI) in a significant percentage of patients, and renal dysfunction seems to be associated with worse prognosis. Patients with chronic kidney disease (CKD) seem to be more susceptible to the severe forms of COVID-19. Patients with renal replacement therapy (RRT) are also a vulnerable population as consequence of their advanced age, underlying comorbidities, impaired immune response, and clustering in hemodialysis centers, with requirements for frequent contact with healthcare services. Kidney transplant patients may be at high-risk due to long-term immunosuppression and comorbidities, hence, managing immunosuppression is imperative. Lastly, renal replacement therapy may be required during COVID-19, and different modalities are discussed based on clinical findings and laboratorial aspects. Therefore, COVID-19 seems to affect kidney by different mechanisms, which contributes for AKI development and increases the severity of the disease. Also, patients with CKD and kidney transplant recipients are at higher risk for COVID-19 and mortality.

Resumo COVID-19 é uma pandemia associada a manifestações clínicas sistêmicas. Neste estudo, apresenta-se revisão narrativa acerca do envolvimento renal na COVID-19. Envolvimento renal parece ser relacionado a efeitos citopáticos diretos, mecanismos imunológicos, efeitos indiretos de outros mediadores no tecido renal, além de disfunção e lesão de outros órgãos. A evolução da COVID-19 pode ser complicada por lesão renal aguda (LRA) em percentual significativo dos pacientes, e a disfunção renal parece ser associada a pior prognóstico. Pacientes com doença renal crônica (DRC) parecem ser mais suscetíveis a formas severas da COVID-19. Pacientes em terapia de substituição renal (TSR) contínua também constituem população vulnerável em razão de idade avançada, comorbidades subjacentes, resposta imune disfuncional e aglomeração em unidades de diálise, com necessidade de visitas frequentes aos serviços de saúde. Pacientes transplantados renais podem estar em alto risco dadas imunossupressão a longo prazo e comorbidades; assim, o manejo da imunossupressão é mandatório. Finalmente, TSR pode ser necessária durante a COVID-19, e diferentes modalidades são discutidas conforme manifestações clínicas e aspectos laboratoriais. Assim, COVID-19 parece acometer os rins por diferentes mecanismos, os quais contribuem para o desenvolvimento de LRA e aumento da severidade da doença. Ainda, pacientes com DRC e transplantados renais apresentam elevado risco para desenvolvimento de COVID-19 e de mortalidade.