Caracterización de la periferia mieloide de los gliomas

Gliomas are the most common primary brain tumors with a mortality rate of 75%. Despite aggressive treatment, aggressive gliomas recur in almost 100% of cases, mainly at or near the margins of resection, so it is of great interest to understand the cellular and molecular context in which the tumor develops. One of the main challenges in the treatment of gliomas is the great inter- and intra-tumoral heterogeneity and the complex tumor microenvironment that favors its progression and immune evasion. Among the cells that participate in the tumor microenvironment, myeloid cells are especially relevant, with tumor-associated macrophages and microglia constituting up to 40% of the tumor mass. However, while the tumor core is well characterized, the periphery of gliomas remains a great unknown. Thus, the neuro-oncology laboratory has begun to study the border niche of gliomas based on single-cell RNA sequencing data, identifying genes specific for the different cell types present in gliomas. This allowed them to characterize proliferative, oligodendrocyte, and endothelial fractions, but the myeloid part remained poorly clustered. However, it is of great relevance to better understand the interaction between glioma and myeloid cells and to expand the current knowledge of the peripheries’ myeloid composition in order to discover new biomarkers and identify different molecular profiles of gliomas. Therefore, the main objective of this work was to provide a better and in-depth characterization of the myeloid environment in gliomas, and especially in the peri-tumoral zone. To this end, myeloid-focused analyses from various scRNAseq databases and survival studies with already measured gene expression data have been carried out. In addition, in order to enrich the myeloid cluster, the expression of canonical markers has been measured in patient samples. Finally, immunohistochemical analysis in mouse glioma models representing different tumor subtypes were performed to validate the genes of interest found in the human samples. An inverse expression pattern between the expression of TREM2 and CD68, which allowed the characterization of two different types of immune environments in gliomas, has been found. In addition, it has been possible to relate the CD68/TREM2 ratio, particularly in a peripheral zone, to the tumor progression. Furthermore, the analysis of the myeloid environment with canonical markers has revealed the ability of microglial markers to distinguish between the tumor core and its periphery. In addition, ITGA4 and TMEM119, and the ratio characterized the tumoral areas, ITGA4/TMEM119 showing a prognosis value in patients. Finally, in the validation of these four genes at the protein level, CD68 and ITGA4 distinguished between the different subtypes of gliomas, while TMEM119 and ITGA4 characterized tumoral areas. In conclusion, this study identified some myeloid markers (ITGA4, TMEM119, TREM2, and CD68), which seem to correlate with different immune profiles related to progression and survival, making them possible prognostic biomarkers. All in all, characterization of the myeloid periphery of gliomas has been achieved, but further studies are needed to obtain more definitive and robust results

CONTRIBUIÇÃO DE FATORES QUÍMICOS E METEOROLÓGICOS PARA A FORMAÇÃO DE OZÔNIO TROPOSFÉRICO EM SÃO PAULO

O ozônio (O3) é um dos poluentes responsáveis pela deterioração da qualidade do ar em áreas urbanas. Trata-se de um poluente secundário, formado na atmosfera a partir de reações fotoquímicas, sendo que sua produção depende tanto de fatores meteorológicos quanto de fatores químicos. Este trabalho tem por objetivo analisar a variabilidade interanual das concentrações de O3 na região metropolitana de São Paulo entre 2005 e 2015, isolando a contribuição de fatores químicos, através da aplicação do filtro Kolmogorov–Zurbenko. Os resultados mostram que a variabilidade das condições meteorológicas explicou de 39 a 52% da variância das concentrações de O3 no período de estudo. Picos de concentração de O3 na componente de longo prazo foram atribuídos majoritariamente a fatores químicos, associados a mudanças no padrão de emissão de precursores. Nos anos em que foram observadas altas concentrações de O3 houve um aumento no consumo de gasolina em relação a etanol

Libro de Actas del XV Congreso de estudiantes de Ciencia, Tecnología e Ingeniería Agronómica

Trabajos científicos, de prácticas, revisiones bibliográficas de estudiantes de la ETSIAAB presentados como comunicaciones orales y pósters

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used