Comparative Effectiveness and Safety of Monoclonal Antibodies (Bevacizumab, Cetuximab, and Panitumumab) in Combination with Chemotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

Background: The last decade has seen the increasing use of biological medicines in combination with chemotherapy containing 5- Fluorouracil/oxaliplatin or irinotecan for the treatment of metastatic colorectal cancer (mCRC). These combinations have resulted in increased progression-free survival (PFS) in patients with mCRC; however, there are remaining concerns over the extent of their effect on overall survival (OS). Published studies to date suggest no major differences between the three currently available monoclonal antibodies (MoAbs); however, there are differences in costs. In addition, there is rising litigation in Brazil in order to access these medicines as they are currently not reimbursed. Objective: To compare the effectiveness and safety of three MoAbs (bevacizumab, cetuximab and panitumumab) associated with fluoropyrimidine-based chemotherapy regimens or compared to fluoropyrimidine-based chemotherapy alone in patients with mCRC through an updated systematic review and meta-analysis with concurrent or non concurrent observational cohort studies to guide the authorities and judiciary. Method: A systematic review and meta-analysis was performed based on cohort studies published in databases up to November 2017. Effectiveness measures include OS, PFS, post-progression survival (PPS), RECIST (Response Evaluation Criteria In Solid Tumors), response rate, metastasectomy and safety. The methodological quality of the studies was also evaluated. Results: 21 observational cohort studies were included. There were statistically significant and clinically relevant benefits in patients treated with bevacizumab versus no bevacizumab mainly around OS, PFS, PPS and the metastasectomy rate, but not for the disease control rates. However, there was an increase in treatment-related toxicities, and concerns with the heterogeneity of the studies. Conclusion: The results pointed to an advantage in favor of bevacizumab for OS, PFS, PPS, and metastasectomy. Although this advantage may be considered clinically modest, bevacizumab represents a hope for increased survival and a chance of metastasectomy for patients with mCRC. However, there are serious adverse events associated with its use, especially severe hypertension and gastrointestinal perforation that need to be considered

Estimulação cerebral profunda na Doença de Parkinson: evidências de estudos de longa duração

A Doença de Parkinson (DP) é uma condição neurodegenerativa crônica que afeta principalmente idosos, mas pode ocorrer em adultos jovens. É a segunda doença neurodegenerativa mais comum, após o Alzheimer. A DP afeta 1% dos indivíduos acima de 60 anos em países industrializados. Sua causa envolve fatores genéticos e ambientais, como exposição a pesticidas e envelhecimento. A Estimulação Cerebral Profunda (DBS) é um tratamento que simula lesões cerebrais, melhorando sintomas motores e não motores. O presente estudo tem como objetivo analisar evidências de estudos sobre a eficácia da DBS no tratamento da DP. Trata-se de uma revisão sistemática de estudos quantitativos que utiliza as bases de dados PubMed (Medline), Cochrane Library e Scientific Electronic Library Online (SciELO) para selecionar artigos científicos. Os estudos incluídos abrangem o período de 2013 a 2023 e estão em inglês, abordando a DBS no tratamento da DP. A DBS melhora diversos sintomas motores e não motores, resultando em uma melhor qualidade de vida para os pacientes. Tais benefícios são sustentados mesmo em estágios avançados da Doença de Parkinson, a qual consiste em fornecer pulsos de corrente elétrica a áreas cerebrais profundas através de eletrodos implantados cirurgicamente, geralmente quando a terapia medicamentosa já não é eficaz. Em um estudo com 82 pacientes, a terapia com DBS resultou em uma redução de ± 52% nos sintomas motores do UPDRS sob medicação antes da cirurgia. A melhora nos sintomas motores com a estimulação, em comparação com a ausência de estimulação e medicação, foi de ± 61% no primeiro ano e ± 39% de 8 a 15 anos após a cirurgia (antes da reprogramação). A medicação foi reduzida em ± 55% após 1 ano e ± 44% após 8 a 15 anos, com a maioria dos pacientes mostrando melhorias após a reprogramação. De acordo com as literaturas analisadas, a DBS é uma terapia eficaz para a DP. Enfatiza-se a importância da inovação contínua e dos novos estudos para explorar as facetas não investigadas desse campo. Com a abordagem dos aspectos clínicos, cirúrgicos, tecnológicos e científicos, destacam-se os benefícios, limitações e desafios a serem superados. Ademais, inovações tecnológicas na DBS, como a estimulação direcional, adaptativa e a telemedicina estão sendo exploradas. Em suma, este artigo fornece evidências sobre os benefícios da DBS na DP, ressaltando a necessidade de pesquisas adicionais para otimizar tal intervenção terapêutica e melhorar a qualidade de vida dos pacientes

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

PERFIL EPIDEMIOLÓGICO DOS PACIENTES USUÁRIOS DE SUBSTÂNCIAS PSICOATIVAS COM AIDS INTERNADOS EM UM HOSPITAL DE REFERÊNCIA EM SALVADOR, BAHIA

Introdução: A infecção pelo HIV tem alta prevalência em pacientes usuários de substâncias psicoativas. Essa associação contribui para piores desfechos de saúde individuais e representa uma significativa barreira no combate à transmissão do vírus e aderência ao tratamento. Objetivos: Apresentar o perfil clínico-epidemiológico dos pacientes usuários de substâncias ilícitas internados com AIDS em um hospital especializado em doenças infecto-contagiosas na capital da Bahia. Métodos: Neste estudo transversal, foi realizada uma análise descritiva dos dados levantados por meio do prontuário eletrônico de pacientes internados no hospital entre julho e outubro de 2022. Foram incluídos pacientes com 18 anos ou mais, portadores do vírus HIV e usuários de maconha, cocaína ou crack. Resultados: Dos 131 prontuários revisados, houve 47 internações de 43 pacientes usuários de substâncias psicoativas com AIDS. Destes: 62,79% (27) eram homens, 79,07% eram heterossexuais, 72,09% eram autodeclarados pardos, 58,14% possuíam ensino fundamental incompleto, 76,74% eram solteiros, 48,84% tinham renda inferior a um salário-mínimo. A idade média dos pacientes foi de 39,27 (Min 18; Max 72) anos, o tempo médio de internação foi de 26,17 dias, 51,16% dos pacientes tiveram pelo menos 1 internação prévia no mesmo hospital, a mediana do CD4/mm3 desses pacientes foi de 132,5 (10 a 1266), e mediana da carga viral foi de 222.702 (26 a 9.868.945); 12 (28,0%) pacientes referiam boa adesão a TARV. 12 (28%) pacientes tiveram o diagnóstico de HIV nessa internação e a média de CD4 nesse grupo foi de 111 cel/mm3. Tuberculose (26,32%), Toxoplasmose (19,3%) foram as principais infecções diagnosticadas durante o internamento. VDRL reagente em 13 (30,2%), HCV 2 (4,6%), Ag Hbs 1 (2,3%) dos pacientes. Desfecho foi alta com melhora em 76,7%, evasão/alta a pedido em 11,64% e 11,64% evoluíram para óbito. Conclusão: Na amostra, houve predomínio de homens adultos, pardos, heterossexuais, com baixo nível de escolaridade e renda. Dentre as causas de internação prevaleceram as coinfecções por doenças oportunistas. Esses apresentaram internações de longa duração, com altos índices de mortalidade, evasão do serviço e reinternação. Para minimizar os danos, são necessárias medidas de saúde pública voltadas para essa população

Mutagenic and Cytotoxicity LQB 123 Profile: Safety and Tripanocidal Effect of a Phenyl-t-Butylnitrone Derivative

Submitted by Sandra Infurna ([email protected]) on 2018-02-27T13:29:45Z No. of bitstreams: 1 rubem_mennabarreto_etal_IOC_2017.pdf: 1911190 bytes, checksum: 4c162cf9427198496253166cb5741a47 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-02-27T13:51:49Z (GMT) No. of bitstreams: 1 rubem_mennabarreto_etal_IOC_2017.pdf: 1911190 bytes, checksum: 4c162cf9427198496253166cb5741a47 (MD5)Made available in DSpace on 2018-02-27T13:51:49Z (GMT). No. of bitstreams: 1 rubem_mennabarreto_etal_IOC_2017.pdf: 1911190 bytes, checksum: 4c162cf9427198496253166cb5741a47 (MD5) Previous issue date: 2017Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Unidade de Desenvolvimento Tecnológico de Triagem de Compostos Químicos para Doenças Negligenciadas com Ênfase Farmacológica contra a Doença de Chagas. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Unidade de Desenvolvimento Tecnológico de Triagem de Compostos Químicos para Doenças Negligenciadas com Ênfase Farmacológica contra a Doença de Chagas. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Biofísica e Biometria. Laboratório de Mutagênese Ambiental. Rio de janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.Universidade do Estado do Rio de Janeiro. Departamento de Química Orgânica. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Unidade de Desenvolvimento Tecnológico de Triagem de Compostos Químicos para Doenças Negligenciadas com Ênfase Farmacológica contra a Doença de Chagas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Química Bioorgânica. Rio de Janeiro, RJ, BrasilUniversidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Unidade de Desenvolvimento Tecnológico de Triagem de Compostos Químicos para Doenças Negligenciadas com Ênfase Farmacológica contra a Doença de Chagas. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Biofísica e Biometria. Laboratório de Mutagênese Ambiental. Rio de janeiro, RJ, BrasilUniversidade do Estado do Rio de Janeiro. Departamento de Química Orgânica. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Unidade de Desenvolvimento Tecnológico de Triagem de Compostos Químicos para Doenças Negligenciadas com Ênfase Farmacológica contra a Doença de Chagas. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia, Entomologia Molecular. Rio de Janeiro, RJ, Brasil.The therapeutic options for Chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease. Therefore, new therapeutical options are mandatory. In the present work, we evaluated the effect of a phenyl-tert-butylnitrone (PBN) derivate, LQB 123, againstTrypanosoma cruziforms. LQB 123 presented a trypanocidal effect against bloodstream trypomastigotes (IC50= 259.4 ± 6.1 μM) and intracellular amastigotes infecting peritoneal macrophages (IC50= 188.2 ± 47.5 μM), with no harmful effects upon the mammalian cells (CC50values greater than 4 mM), resulting in a high selectivity index (CC50/IC50> 20). Additionally, metacyclic trypomastigotes submitted to LQB 123 presented an IC50of about 191.8 ± 10.5 μM and epimastigotes forms incubated with different concentrations of LQB 123 presented an inhibition of parasite growth with an IC50of 255.1 ± 3.6 μM. Finally, we investigated the mutagenic potential of the nitrone by theSalmonella/microsome assay and observed no induction of mutagenicity even in concentrations as high as 33000 μM. Taken together, these results present a nonmutagenic compound, with trypanocidal activity against all relevant forms ofT. cruzi, offering new insights into CD treatment suggesting additional in vivo tests