Índice neutrófilo-linfocito e índice plaquetas-linfocito: herramientas pronósticas del cáncer de pulmón

El cáncer de pulmón es la neoplasia maligna que causa mayor mortalidad en el mundo. Dentro de los factores pronósticos de esta entidad, se encuentran el índice neutrófilo-linfocito y el índice plaquetas-linfocito, parámetros hematológicos que se utilizan para evaluar la inflamación y la respuesta inmunitaria en el cuerpo humano. Se realizó una revisión bibliográfica con el objetivo de exponer el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón, teniendo en cuenta la evidencia científica publicada hasta el momento. Se estudiaron 46 artículos, 28 de los cuales resultaron seleccionados para la elaboración de la investigación. Se emplearon como criterios de selección la calidad de los estudios, el nivel de actualización sobre el tema en cuestión, así como la fiabilidad de la fuente. Se usaron los recursos disponibles en la red Infomed para la selección de la información, entre ellos: PubMed, SciELO, EBSCO, Cumed, LILACS y Scopus, además de Medline, Academic Search Premier y MedicLatina. Se expuso el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón de células no pequeñas, en todos los estadios y con modalidades terapéuticas diferentes.

Lung cancer is the malignant neoplasm that causes higher mortality in the world. Among the prognostic factors of this entity are the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, hematological parameters that are used to assess inflammation and the immune response in the human body. A bibliographic review was carried out with the objective of exposing the value of the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool for lung cancer, taking into account the scientific evidence published to date. A total of 46 articles were studied, of which 28 were selected for the development of the research. The quality of the studies, the level of updating on the subject in question, as well as the reliability of the source was used as selection criteria. The resources available in the Infomed network were used to select the information, including PubMed, SciELO and EBSCO, Cumed, LILACS and Scopus, as well as Medline, Academic Search Premier and MedicLatina databases. The value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool in non-small cell lung cancer at all stages and with different therapeutic modalities was exposed.

Índice neutrófilo linfocito como predictor de infección del sitio quirúrgico en cirugía abdominal urgente

Introducción: Las infecciones del sitio quirúrgico representan una carga significativa en relación con la morbilidad, la mortalidad y costos adicionales. Por lo tanto, la prevención es importante. Objetivo: Comparar el índice neutrófilos-linfocitos con la escala SENIC para predecir infección del sitio quirúrgico en pacientes que sufrieron una cirugía abdominal de urgencia. Materiales y Métodos: Estudio transversal analítico, realizado en el Hospital de Alta Especialidad de Veracruz en expedientes de pacientes post-operados de urgencia, valorándose la escala SENIC (que incluye tipo de cirugía, duración del procedimiento, grado de asepsia de la intervención y 3 o más diagnósticos posoperatorios) y el índice neutrófilos-linfocitos (definido como la razón neutrófilos sobre linfocitos). Resultados: La edad promedio de los pacientes fue de 47,7 ± 18,7 años, con un predominio del sexo masculino 83 (62%), la estancia hospitalaria media fue de 29,7 ± 14,7 días, los procedimientos fueron la laparotomía exploradora en 57 (42,2%) y la apendicectomía en 26 (19,2%). Se aisló Escherichia coli en 27 (30%). Se obtuvo una sensibilidad de 69% y especificidad de 58% para el índice neutrófilos-linfocitos y para SENIC una sensibilidad 45% y una especificidad de 73%. Las estadísticas C para el índice neutrófilos-linfocitos y SENIC fueron 0,603 (IC: 0,524 − 0,682) y 0,668 (IC 95%: 0,588 − 0,749), respectivamente. Discusión y Conclusión: Ambos métodos muestran una precisión predictiva similar para infección del sitio quirúrgico, si bien calcular el índice neutrófiloslinfocitos es mucho más rápido y sencillo.

Introduction: Surgical site infections represent a significant burden in relation to morbidity, mortality, and additional costs. Therefore, prevention is important. Objective: To compare the neutrophil-lymphocyte index with the SENIC scale to predict surgical site infection in patients who underwent emergency abdominal surgery. Materials and Methods: Analytical cross-sectional study, carried out at the Hospital de Alta Especialidad de Veracruz in records of emergency post-operative patients, evaluating the SENIC scale (which includes type of surgery, duration of the procedure, degree of asepsis of the intervention and 3 or more postoperative diagnoses) and the neutrophil-to-lymphocyte ratio (defined as the ratio of neutrophils to lymphocytes). Results: The average age of the patients was 47.7 ± 18.7 years, with a predominance of males 83 (62%); the mean hospital stay was 29.7 ± 14.7 days, the procedures were exploratory laparotomy in 57 (42.2%) and appendectomy in 26 (19.2%). Escherichia coli was isolated in 27 (30%). A sensitivity of 69% and specificity of 58% was obtained for the neutrophil-lymphocyte index and for SENIC a sensitivity of 45% and a specificity of 73%. The C statistics for the neutrophil-lymphocyte ratio and SENIC were 0.603 (CI: 0.524 − 0.682) and 0.668 (95% CI: 0.588 − 0.749), respectively. Discussion and Conclusion: Both methods show similar predictive accuracy for surgical site infection, although calculating the neutrophil-lymphocyte ratio is much faster and easier.

Índice neutrófilo/linfocito en anestesia general con ventilación controlada por volumen versus ventilación controlada por presión: ensayo clínico aleatorizado / Neutrophil/lymphocyte ratio in general anesthesia with volume-controlled ventilation versus pressure-controlled ventilation: a randomized clinical trial

Resumen: Introducción: se ha demostrado que la ventilación mecánica induce la producción de citocinas proinflamatorias. El IN/L es un parámetro sencillo que se utiliza para evaluar el estado inflamatorio. Objetivo: comparar los promedios y porcentajes del índice neutrófilo/linfocito (IN/L) elevado, entre pacientes con anestesia general con ventilación mecánica controlada por volumen (VMCV) y ventilación mecánica controlada por presión (VMCP). Material y métodos: se seleccionaron adultos ≥ 18 años, ASA I-III con cirugía electiva y anestesia general. Ensayo clínico aleatorizado: 25 pacientes con VMCV y 25 con VMCP. A todos los pacientes se les determinó dos biometrías hemáticas: antes y 2 horas después de la cirugía. El IN/L fue medido en forma de razón y dicotómica (< 3 o ≥ 3). Análisis estadístico: se utilizaron las pruebas t de Student, χ2 y McNemar. Resultados: se estudiaron 50 pacientes (27 mujeres y 23 hombres) con un promedio de edad de 47 ± 16 años. El grupo de VMCV tuvo tendencia a presentar valores más bajos de promedios y porcentajes IN/L; sin embargo, no fue estadísticamente significativa (p = 0.06). En la comparación pareada ambos grupos presentaron incremento estadísticamente significativo de los promedios y porcentajes de IN/L. No obstante, el porcentaje de IN/L > 3 en el grupo de VMCP fue de 64%, mientras que en el grupo de VMCV fue de 40%. Conclusiones: la VMCV presenta promedios y porcentajes más bajos del IN/L comparados con VMCP; sin embargo, no fueron estadísticamente significativos.

Abstract: Introduction: it has been shown that mechanical ventilation induces production of proinflammatory cytokines. The Neutrophil-to-lymphocyte ratio (N/L r) is a simple parameter that is used to assess the inflammatory state. Objective: to compare the means and percentages of elevated neutrophil/lymphocyte ratio (N/L r) in patients under general anesthesia with volume-controlled mechanical ventilation (VCMV) and pressure-controlled mechanical ventilation (PCMV). Material and methods: adults ≥ 18 years old, ASA I-III, with elective surgery and general anesthesia. Randomized clinical trial: 25 patients with VCMV and 25 with PCMV. All patients had two blood counts determined: before and 2 hours after surgery. N/L r was measured as a ratio and dichotomous (< 3 or ≥ 3). Statistical analysis: the t-Student, χ2 and McNemar tests were used. Results: 50 patients (27 women and 23 men) with a mean age of 47 ± 16 years (range 18-84 years) were studied. The VCMV group tended to present lower values of means and percentages N/L r, however, it was not statistically significant (p = 0.06). In the paired comparison, both groups presented a statistically significant increase in the means and percentages of N/L r. However, the percentage of N/L r > 3 in the PCMV group was 64%, while in the VCMV group it was 40%. Conclusions: the VCMV presents lower means and percentages of N/L r compared to PCMV, however, they were not statistically significant.

Asociación entre índice neutrófilo/linfocito como biomarcador de mortalidad en pacientes con quemaduras mayores durante el periodo del 01 de febrero de 2020 al 28 de enero de 2022 / Association between neutrophil/lymphocyte ratio as a biomarker of mortality in patientswith major burns during the period February 1, 2020 to January 28, 2022 / Associação entre a relação neutrófilo/linfócito como biomarcador de mortalidade empacientes com grandes queimaduras no período de 1º de fevereiro de 2020 a 28 de janeiro de 2022

resumen está disponible en el texto completo

Abstract: Introduction: burns are a serious public health problem, with several studies estimating that more than 11 million people were affected by burn injuries with approximately 300,000 deaths worldwide. Studies showed that the main causes of death were inhalation injuries, infection, and metabolic and hemodynamic complications ending in multi-organ failure. It has been shown that the increase in the systemic inflammatory response, whose parameters can be easily obtained, can be useful and directly related to poor prognosis. Several clinical studies indicate that the ratio of neutrophils to lymphocytes, an indicator of systemic inflammatory response, can signify the presence of inflammation in some diseases such as diabetes, coronary artery disease, cholangitis, rheumatoid arthritis, and recently COVID-19. Objective: to know the association between the neutrophil lymphocyte index as a biomarker of mortality in patients with major burns. Material and methods: an observational, retrospective, descriptive, longitudinal study will be carried out: with a user population of the National Center for Research and Attention to Burned Patients (CENIAQ) of the Luis Guillermo Ibarra Ibarra National Rehabilitation Institute. A review of the clinical records of the patients treated in the period will be carried out during the period from February 1, 2020 to February 28, 2022, the data of admission and discharge will be taken into account, as well as initial laboratory studies. The information will be recorded in an Excel spreadsheet to be later analyzed in the SPSS software, the results will be obtained and finally their analysis will be carried out. Results: in the analyzed population we found that the average age is 40 years, it was also found that the most affected gender in this population corresponds to the male gender with 81.2%. It was also found that, within the diagnoses of the population studied, fire burn was the one that most affected the population, this being 67.1% of all diagnoses. However, in this study no significant difference was found in the neutrophil lymphocyte index with respect to the type of burn. In our analysis, the neutrophil lymphocyte index was included as a biochemical predictor of mortality, since high levels of this index at admission are associated with increased mortality. In our population, a significant difference was found between the groups with a fatal clinical outcome and those who recovered, which is why it can be considered as a predictor of mortality in these patients since they presented a p value < 0.023, data that is consistent with what is reported in the international literature where the Neutrophil lymphocyte index value can be used as a predictor of mortality. Conclusions: an association was found between the elevation of the neutrophil/lynphocyte ratio and mortality in patients with severe burns.

Resumo: Introdução: as queimaduras são um grave problema de saúde pública, onde estima-se em diversos estudos que mais de 11 milhões de pessoas foram acometidas por queimaduras com aproximadamente 300.000 mortes em todo o mundo. Estudos mostraram que as principais causas de morte foram lesões inalatórias, infecções e complicações metabólicas e hemodinâmicas que culminaram em falência de múltiplos órgãos. Tem sido demonstrado que o aumento da resposta inflamatória sistêmica, cujos parâmetros podem ser facilmente obtidos, pode ser útil e estar diretamente relacionado ao mau prognóstico. Vários estudos clínicos indicam que a proporção de neutrófilos para linfócitos, um indicador de resposta inflamatória sistêmica, pode significar a presença de inflamação em algumas doenças como diabetes, doença arterial coronariana, colangite, artrite reumatóide e recentemente COVID-19. Objetivo: conhecer a associação entre o índice neutrófilo-linfócito como biomarcador de mortalidade em pacientes com grandes queimaduras. Material e métodos: será realizado um estudo observacional, descritivo, retrospectivo, longitudinal: com a população usuária do Centro Nacional de Pesquisa e Atenção ao Paciente Queimado (CENIAQ), do Instituto Nacional de Reabilitação Luis Guillermo Ibarra Ibarra. Realizaremos uma revisão dos prontuários clínicos dos pacientes atendidos no período de 1º de fevereiro de 2020 a 28 de fevereiro de 2022, serão levados em consideração os dados de admissão e alta, bem como os estudos laboratoriais iniciais. As informações serão registradas em planilha Excel para posteriormente serem analisadas no software SPSS, serão obtidos os resultados e por fim será realizada a análise. Resultados: na população analisada verificamos que a média de idade é de 40 anos, constatou-se também que o gênero mais acometido nesta população corresponde ao gênero masculino com 81.2%. Constatou-se também que, dentro dos diagnósticos da população estudada, a queimadura por fogo foi o que mais afetou a população, sendo este 67.1% do total de diagnósticos. No entanto, neste estudo não foi encontrada diferença significativa no índice neutrófilo-linfócito em relação ao tipo de queimadura. Em nossa análise, foram incluídos o índice neutrófilo-linfócito como preditor bioquímico de mortalidade, uma vez que altos níveis desse índice na admissão estão associados a aumento da mortalidade. Em nossa população, foi encontrada diferença significativa entre os grupos com desfecho clínico fatal e os recuperados, motivo pelo qual pode ser considerado como preditor de mortalidade nesses pacientes, pois apresentaram valor de p < 0.023, dado compatível com o relatado em a literatura internacional onde o valor do índice neutrófilo-linfócito pode ser utilizado como preditor de mortalidade. Conclusões: encontrou-se associação entre a elevação do índice neutrófilo/linfócito e mortalidade em pacientes com queimaduras graves.

Prognostic role of neutrophil-to-lymphocyte ratio to laryngeal squamous cell carcinoma: a meta-analysis / Papel prognóstico da relação neutrófilo-linfócito no carcinoma espinocelular da laringe: uma metanálise

Abstract Introduction New evidence suggests that the ratio of neutrophils to lymphocytes is associated with the prognosis of other carcinoma, but the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma remains controversial. Objective The objective of this meta-analysis was to clarify the prognostic effectiveness of the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma. Methods According to the meta-analysis of the free guide, we searched EMBASE, Pubmed, the Cochrane Library databases. The ratio of neutrophils to lymphocytes of laryngeal squamous cell carcinoma patients was evaluated using mean standard vehicle and confidence interval. The overall survival, disease-free survival and progression free survival of patients with laryngeal squamous cell carcinoma were expressed by standard mean carrier method and confidence interval. The risk ratio of 95% confidence interval was used as an evaluation index for patients with laryngeal squamous cell carcinoma. Results Eight studies, including 1780 patients, used a variety of different end values to classify the ratio of neutrophils to lymphocytes (range 1.78-4.0). Among the eight studies that reported risk ratio of the overall survival, the higher median value was 2.72, and 2 of 4 studies reported disease-free survival results. The critical value of ratio of neutrophils to lymphocytes and overall survival deterioration (risk ratio = 1.68, 95% confidence interval 1.43-1.99, p< 0.001), disease-free survival (risk ratio = 2.09, 95% confidence interval 1.62-2.6, p< 0.001) and progression free survival (risk ratio = 1.92, 95% confidence interval 1.75-2.10, p< 0.001) was associated with with laryngeal aquamous cell carcinoma. The ratio of neutrophils to lymphocytes had prognostic value for laryngeal squamous cell carcinoma. Conclusion The results of this meta-analysis showed that the increase of neutrophils to lymphocytes ratio was related to poor prognosis of laryngeal squamous cell carcinoma. The neutrophils to lymphocytes ratio may serve as a cost-effective prognostic biomarker of poor prognosis of laryngeal squamous cell carcinoma. More high-quality prospective trials are needed to assess the practicability of evaluating the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma.

Resumo Introdução Novas evidências sugerem que a relação neutrófilo-linfócito está associada ao prognóstico de vários carcinomas, mas a relação neutrófilo-linfócito no carcinoma espinocelular da laringe ainda permanece controversa. Objetivo Esclarecer a eficácia prognóstica da relação neutrófilo-linfócito no carcinoma espinocelular de laringe. Método De acordo com as diretrizes de metanálise, conduzimos uma busca nas bases de dados Embase, PubMed, e Cochrane Library. A relação neutrófilo-linfócito de pacientes com carcinoma espinocelular de laringe foi avaliado com a diferença de médias padronizadas e intervalo de confiança. A sobrevida global, sobrevida livre de doença e sobrevida livre de progressão de pacientes com carcinomaespinocelular de laringe foram expressas pelo método da diferença de médias padronizadas e intervalo de confiança. A razão de risco do intervalo de confiança 95% foi usada como um índice de avaliação para pacientes com carcinoma espinocelular de laringe. Resultados Oito estudos, que incluíram 1.780 pacientes, usaram uma variedade de valores finais diferentes para classificar a relação neutrófilo-linfócito (intervalo de 1,78-4,0). Entre os oito estudos que relataram a razão de risco de sobrevida global, o maior valor médio foi de 2,72 e 2 de 4 estudos relataram resultados com sobrevida livre de doença. O valor crítico de relação neutrófilo-linfócito e deterioração da sobrevida global (razão de risco = 1,68, intervalo de confiança 95% 1,43-1,99, p ˂ 0,001), sobrevida livre de doença (razão de risco = 2,09, intervalo de confiança 95% 1,62-2,6, p ˂ 0,001) e sobrevida livre de progressão (razão de risco = 1,92, intervalo de confiança 95% 1,75-2,10, p ˂ 0,001) foi associado com carcinoma espinocelular de laringe. A relação neutrófilo-linfócito tem valor prognóstico para carcinoma espinocelular de laringe. Conclusão Os resultados da metanálise mostraram que o aumento da relação neutrófilo-linfócito estava relacionado ao mau prognóstico do carcinoma espinocelular de laringe. A relação neutrófilo-linfócito pode servir como um biomarcador custo-efetivo de prognóstico do carcinoma espinocelular de laringe. Entretanto, mais estudos prospectivos de alta qualidade são necessários para avaliar a sua praticabilidade.

Prognostic value of pre-operative peripheral inflammation markers in patients with squamous cell carcinoma of the external auditory canal / Valor prognóstico dos marcadores de inflamação periférica pré-operatórios em pacientes com carcinoma espinocelular do meato acústico externo

Abstract Introduction: Squamous cell carcinoma of the external auditory canal is a rare entity. Previous studies have suggested predictors for tumor recurrence. However, most of the prognostic factors were from the clinicopathological aspect. Objective: This study aims to analyze the correlation between pre-operative peripheral inflammation markers and survival outcomes, in order to identify prognostic biomarkers for patients with squamous cell carcinoma of the external auditory canal. Methods: We retrospectively analyzed patients diagnosed with squamous cell carcinoma of the external auditory canal who underwent surgery at our institute. The pre-operative circulating inflammatory markers, such as the neutrophil, lymphocyte, platelet, and monocyte counts were measured and their ratios including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio were calculated. The prognostic value of the measured hematologic parameters in relation to the survival outcomes was also evaluated. Results: A total of 83 patients were included, of which 26 patients showed tumor recurrence and 57 without recurrence. Neutrophil counts and neutrophil-to-lymphocyte ratio were closely connected with tumor stage. In the patients with recurrence, neutrophil counts, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were elevated (p< 0.0001, p< 0.0001 and p = 0.001), while lymphocyte counts and lymphocyte-to-monocyte ratio were decreased (p = 0.013 and p = 0.016, respectively). The receiver operating curve analysis indicated that pre-operative neutrophil-to-lymphocyte ratio is a potential prognostic marker for recurrence of squamous cell carcinoma of the external auditory canal (area under curve = 0.816), and the cut-off points was 2.325. Conclusions: Pre-operative neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte are significantly correlated with tumor recurrence in patients with external auditory canal squamous cell carcinoma. Furthermore, neutrophil-to-lymphocyte ratio may be unfavorable prognostic factors of this disease.

Resumo Introdução: O carcinoma espinocelular do meato acústico externo é uma doença rara. Estudos anteriores sugeriram preditores de recorrência do tumor. Entretanto, a maioria dos fatores prognósticos se originou do aspecto clínico-patológico. Objetivo: Analisar a correlação entre marcadores inflamatórios periféricos pré-operatórios e os desfechos de sobrevida e identificar biomarcadores prognósticos para pacientes com carcinoma espinocelular do meato acústico externo. Método: Analisamos retrospectivamente pacientes com diagnóstico de carcinoma espinocelular do meato acústico externo submetidos à cirurgia em nosso instituto. Os marcadores inflamatórios circulantes pré-operatórios, como as contagens de neutrófilos, linfócitos, plaquetas e monócitos, foram medidos e as suas relações calculadas, inclusive as relações neutrófilos/linfócitos, plaquetas/linfócitos e linfócitos/monócitos. O valor prognóstico dos parâmetros hematológicos medidos em relação aos desfechos de sobrevida também foi avaliado. Resultados: Foram incluídos 83 pacientes, entre os quais 26 apresentaram recorrência tumoral e 57 não apresentaram. A contagem de neutrófilos e a relação neutrófilo/linfócito estavam intimamente associadas ao estágio do tumor. Nos pacientes com recorrência, a contagem de neutrófilos, a relação neutrófilos/linfócitos e a relação plaquetas/linfócitos eram elevadas (p < 0,0001, p > 0,0001 e p = 0,001), enquanto a contagem de linfócitos e a relação linfócitos/monócitos estavam diminuídas (p = 0,012 ep = 0,016, respectivamente). A análise da curva, Receiver Operating Characteristic, indicou que a relação neutrófilos/linfócitos pré-operatória era um potencial marcador prognóstico para a recorrência de carcinoma espinocelular do meato acústico externo (Área sob a curva = 0,816) e o ponto de corte foi de 2,325. Conclusão: A contagem pré-operatória de neutrófilos e linfócitos, as relações neutrófilos/linfócitos, plaquetas/linfócitos e linfócitos/monócitos estão significativamente correlacionadas com a recorrência do tumor em pacientes com carcinoma espinocelular do meato acústico externo. Além disso, a relação neutrófilos/linfócitos pode ser um fator prognóstico desfavorável dessa doença.

Studying Juvenile Idiopathic Arthritis through a Network Medicine Approach / Estudando a Artrite Idiopática Juvenil mediante uma abordagem de medicina de redes

Juvenile Idiopathic Arthritis (JIA) is a group of inflammatory conditions of unknown etiology whose underlying molecular pathophysiology is still not well characterized. Several studies have attempted to fill this gap by characterizing the gene expression profiles of JIA patients. However, there is a lack of systematic assessment of the reliability of these transcriptome results on the disease classification, prescription, and monitoring. In addition, despite this disease is more common in females, none of these studies have tried to assess the impact of sex on disease pathophysiology. In this project, we performed a comprehensive systematic review and a gene expression meta-analysis to reveal the core molecular JIA pathophysiology taking into consideration the patient sex. We gathered and cataloged more than 60,000 entries of genomic features reported as JIA-related in the functional genomics literature, and found a dramatic disparity among the JIA transcriptome studies. Near 15,000 genes have been reported as perturbed in JIA leukocytes. Less than one percent of these genes were reported in at least a quarter of the reviewed studies. We then removed the study-specific analytical bias by re-analyzing more than 700 unique pediatric transcriptome profiles from nine JIA studies using a common analytical framework. The differential expression results from different studies were combined using a random effect model meta-analysis approach. We implemented this differential gene expression meta-analysis methodology in the MetaVolcanoR R package that we made available in Bioconductor. Using this package, we confirmed several gene expression signatures previously associated with JIA and uncover new genes whose expression was perturbed in JIA patients. The effect sizes of the topmost reported perturbed genes coincide with our meta-analysis results. Through a meta-coexpression approach, we characterized the cell type signatures of circulating leukocytes in the JIA affected children. Additionally, we characterized the JIA sexual dimorphism. We found that systemic JIA female patients over-activate a gene expression signature which comprises early myelocytes and band neutrophil expression markers. This signature is correlated with the disease status and response to IL-1 receptor blockade. This suggests that sJIA pathophysiology is characterized by a sexually dimorphic neutrophilia that impacts disease progression and the response to anti-IL-1 treatments. We further assessed this immature neutrophil and female-biased signature in other contexts. We found that this signature presents a sex-dependent expression over human lifetime, in other inflammatory diseases, and its expression increases during pregnancy

A Artrite Idiopática Juvenil (AIJ) é um grupo de condições inflamatórias de etiologia desconhecida, cuja patofisiologia molecular subjacente ainda não está bem caracterizada. Vários estudos tentaram preencher essa lacuna, caracterizando os perfis de expressão gênica de pacientes com AIJ. No entanto, há uma falta de avaliação sistemática desses resultados transcriptômicos na classificação, prescrição e monitoramento da doença. Além disso, apesar de esta doença ser mais comum em mulheres, nenhum desses estudos tentou avaliar o impacto do sexo na fisiopatologia da doença. Neste projeto, realizamos uma revisão sistemática abrangente e uma metanálise de expressão gênica para revelar a fisiopatologia molecular da AIJ levando em consideração o sexo do paciente. Reunimos e catalogamos mais de 60.000 entradas de características genômicas reportadas como relacionadas à AIJ na literatura. Entre os estudos de transcriptoma, encontramos uma disparidade dramática. Cerca de 15.000 genes foram reportados como perturbados nos leucócitos da AIJ, sendo que menos de um por cento desses genes foram relatados em pelo menos um quarto dos estudos revisados. Em seguida, re-analisamos mais de 700 transcriptomas pediátricos de nove estudos usando uma abordagem analítica comum. Os resultados de expressão diferencial foram combinados usando meta-análise de modelo de efeitos aleatórios. Implementamos esta abordagem de meta-análise de expressão gênica diferencial no pacote MetaVolcanoR R que disponibilizamos no Bioconductor. Usando este pacote, confirmamos várias assinaturas de expressão gênica previamente associadas à AIJ e descobrimos novos genes cuja expressão está perturbada em pacientes com AIJ. Os tamanhos dos efeitos dos genes mais reportados como perturbados coincidem com os resultados da nossa meta-análise. Por meio de uma análise de meta-co-expressão, caracterizamos as assinaturas dos tipos de leucócitos circulantes. Além disso, caracterizamos o dimorfismo sexual da AIJ. Descobrimos que pacientes do sexo feminino com AIJ sistêmica super-ativam genes característicos de mielócitos precoces e neutrófilos bastonetes. Esta assinatura está correlacionada com o estado clínico da doença e à resposta ao tratamento por bloqueio do receptor de IL-1. Isto sugere que a fisiopatologia da AIJs é caracterizada por uma neutrofilia sexualmente dimórfica que afeta a progressão da doença e a resposta aos tratamentos anti-IL-1. Avaliamos ainda esta assinatura neutrofílica em outros contextos. Descobrimos que essa assinatura apresenta uma expressão dependente do sexo ao longo da vida humana, em outras doenças inflamatórias, e sua expressão aumenta durante a gravidez

Índice neutrófilo-linfocito, relación plaquetas-linfocito y distribución de la anchura del eritrocito en pacientes con preeclampsia / Neutrophil-to-lymphocyte ratio, plateletto- lymphocyte ratio, and erythrocyte width distribution. and erythrocyte width distribution in patients with preeclampsia

Resumen OBJETIVO: Comparar el índice neutrófilo-linfocito, la relación plaquetas-linfocito y la distribución de la anchura del eritrocito de mujeres con preeclampsia con o sin criterios de severidad y los de mujeres sin ésta. MATERIALES Y MÉTODOS: Estudio retrospectivo, de casos y controles, efectuado en mujeres con y sin preeclampsia atendidas entre enero y diciembre de 2019. RESULTADOS: Se estudiaron 70 mujeres con preeclampsia y 70 con embarazo sin esta complicación. El índice neutrófilo-linfocito fue significativamente mayor en las mujeres con preeclampsia (4.11 ± 2.76; IC95%: 3.47-4.75) que en las mujeres sin esta complicación (2.99 ± 1.6; IC95%: 2.62-3.36; p = 0.004), similar a la relación plaquetas-linfocitos (117.61 ± 47.53; IC95%:106.48-128.24 vs 97.64 ± 43.67; IC95%: 87.41-107.87; p = 0.006) y para la distribución de la anchura del eritrocito (14.46 ± 1.9; IC95%: 14.02-14.9 vs 13.56 ± 1.38; IC95%: 13-13.72; p = 0.0002). Ninguno de estos parámetros logró discriminar entre las pacientes con preeclampsia con o sin criterios de severidad. CONCLUSIÓN: Un índice neutrófilo-linfocito ≥ 5.1 y una relación plaquetas-linfocito ≥ 113.1 son capaces de discriminar de manera adecuada entre preeclampsia con o sin criterios de severidad.

Abstract OBJECTIVE: To compare the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and erythrocyte width distribution, of women with preeclampsia with or without severity criteria and those of women without. MATERIALS AND METHODS: Retrospective case-control study in 70 women with preeclampsia and 70 with normal pregnancy between January and December 2019. RESULTS: Seventy women with preeclampsia and 70 with pregnancy without this complication were studied. The neutrophil-lymphocyte ratio was significantly higher in women with preeclampsia (4.11 ± 2.76; 95%CI: 3.47-4.75), than in women with normal pregnancies (2.99 ± 1.6; 95%CI: 2.62-3.36; p = 0.004); which is similar for the platelet-lymphocyte ratio (117.61 ± 47.53, 95%CI: 106.48-128.24 vs 97.64 ± 43.67; 95%CI: 87.41-107.87; p = 0.006) and for the distribution of the width of the erythrocyte; (14.46 ± 1.9, CI95%: 14.02-14.9 vs 13.56 ± 1.38; CI95%: 13-13.72; p = 0.0002). None of these parameters was able to discriminate between patients with preeclampsia with or without severity criteria. A neutrophil-lymphocyte ratio ≥ 5.1 discriminates between women with a normal pregnancy and those with preeclampsia with or without severity criteria [area under the curve of 0.746, (95%CI: 0.664-0.827)], sensitivity 42%, specificity 91%, positive predictive value 82%, negative predictive value 60% and Odds Ratio 7.1 (95%CI: 2.7-18.6, p = 0.001). The platelet-lymphocyte ratio ≥ 113.4 can discriminate between women with a normal pregnancy and preeclampsia with or without severity criteria, with an area under the curve of 0.617 (95% CI 0.525-0.709). CONCLUSION: A neutrophil-lymphocyte ratio ≥ 5.1, and a platelet-lymphocyte ratio ≥ 113.1 are able to adequately discriminate between patients with normal pregnancy and those with preeclampsia with or without severity criteria.

Síndrome pulmón-riñón en pacientes con hallazgos incidentales de agentes infecciosos / Pulmonary-renal syndrome in patients with incidental findings of infectious agents

El síndrome pulmón-riñón (SPR) o síndrome reno-pulmonar es la combinación de glomerulonefritis aguda rápidamente progresiva (GNARP) y hemorragia alveolar difusa (HAD) de causa autoinmune. El SPR fue inicialmente descrito por Goodpasture en el contexto del síndrome anti-membrana basal glomerular (MBG). Actualmente, las vasculitis asociadas a ANCA (VAA) explican el 60% (rango 56­77.5%) de casos, el síndrome de Goodpasture el 15% (12.5­17.5%), y un 10% de casos se deben a otras causas. El SPR presenta un gran espectro clínico, desde la capilaritis pulmonar fulminante con HAD y falla respiratoria aguda, hasta formas más sutiles de enfermedad sólo detectables mediante lavado bronquio-alveolar (LBA). El objetivo de este estudio es presentar la primera serie peruana de SPR asociada a agentes infecciosos. Reportamos 3 casos, dos correspondieron a lupus eritematoso sistémico y uno a vasculitis asociada a poliangeítis microscópica. El primer caso se asoció a sobreinfección por C. tropicalis; el segundo caso a A. fumigatus y C. albicans; y el tercero a infestación por A. lumbricoides. Todos los casos se presentaron en mujeres, requirieron soporte ventilatorio invasivo y hemodiálisis, y dos resultaron letales. Concluimos que, el SPR es una condición clínica grave comúnmente asociada a sobreinfecciones o infestaciones, y que conlleva una elevada morbilidad y mortalidad. Puesto que no existen características clínicas específicas, resulta crucial tener un alto índice de sospecha. Las investigaciones pertinentes­pruebas inmunológicas, imagenológicas, y biopsia cutánea, renal y/o pulmonar­para precisar la etiología deben realizarse sin demora ya que el tratamiento precoz puede cambiar el pronóstico de estos pacientes(AU)

Pulmonary-renal syndrome (PRS) or reno-pulmonary syndrome is the combination of acute rapidly progressive glomerulonephritis (RPGNARP) and autoimmune diffuse alveolar hemorrhage (DAH). RPS was initially described by Goodpasture in the context of anti-glomerular basement membrane (GBM) syndrome. Currently, ANCA-associated vasculitides (AAV) explain 60% (range 56­77.5%) of cases, Goodpasture syndrome 15% (12.5­17.5%), and 10% of cases are due to other causes. PRS presents a wide clinical spectrum, from fulminant pulmonary capillaritis with ADH and acute respiratory failure, to subtler forms of disease that can only be detected by bronchoalveolar lavage (BAL). The objective of this study is to present the first Peruvian series of SPR associated with infectious agents. We report 3 cases, two corresponded to systemic lupus erythematosus and one to vasculitis associated with microscopic polyangiitis. The first case was associated with superinfection by C. tropicalis; the second case to A. fumigatus and C. albicans; and the third to infestation by A. lumbricoides. All cases occurred in women, required invasive ventilatory support and haemodialysis, and two were fatal. We conclude that SPR is a serious clinical condition commonly associated with superinfections or infestations, and that it carries high morbidity and mortality. Since there are no specific clinical features, a high index of suspicion is crucial. Relevant investigations­immunological tests, imaging tests, and skin, kidney, and/or lung biopsies­to specify the etiology should be carried out without delay, since early treatment can change the prognosis of these patients(AU)

Elevación del índice neutrófilo/linfocito y su relación con la proteína C reactiva en pacientes con diabetes mellitus tipo 2 / Elevation of the neutrophil/lymphocyte ratio and its relationship to C-reactive protein in patients with type 2 diabetes mellitus

Introducción: la proporción entre el recuento absoluto de neutrófilos y el recuento absoluto de linfocitos (índice de neutrófilos/linfocitos, INL) se ha convertido en los últimos años en un marcador crucial de inflamación sistémica, y se ha descrito que su elevación se relaciona con numerosas enfermedades inflamatorias crónicas. Objetivos: determinar el índice de neutrófilos/linfocitos (INL) en pacientes con diabetes mellitus tipo 2 (DM2), comparar con no diabéticos y establecer su correlación con la concentración de proteína C reactiva ultrasensible en una población de la localidad de Riobamba, Ecuador. Materiales y métodos: se realizó una investigación de tipo descriptiva, correlacional, de corte transversal, en el período comprendido desde julio de 2019 a febrero de 2020. Se seleccionaron 80 individuos para participar en el proyecto: 25 sujetos controles y 55 pacientes con diagnóstico de DM2. A cada sujeto se le extrajo una muestra de sangre en ayunas para la determinación de glucosa, colesterol total, triglicéridos, HDL colesterol, LDL colesterol, proteína C reactiva ultrasensible (PCR-us), hemoglobina glicosilada (HbA1c), recuento total de leucocitos, neutrófilos y linfocitos. Resultados: se encontró un incremento significativo en la concentración de glucosa (p<0,0001), HbA1c (p<0,0001), índice de masa corporal (IMC) (p<0,0001), PCR-us (p<0,0001), recuento absoluto de neutrófilos (p=0,001), recuento absoluto de linfocitos (p=0,04) e INL (p=0,0005), y una reducción significativa del HDL colesterol (p=0,02) en los pacientes con DM2 vs los controles. Se observó una correlación positiva (p<0,0001; r=0,7774) entre el INL y la PCR-us en los pacientes con DM2. Conclusiones: los pacientes con DM2 experimentaron elevación en el INL que se correlacionó con el incremento en la concentración de la PCR-us.

Introduction: the ratio between the absolute neutrophil count and the absolute lymphocyte count (neutrophil/lymphocyte ratio, NLR) has become a crucial marker of systemic inflammation in recent years, and its elevation has been described as being related to numerous chronic inflammatory diseases. Objectives: to determine the neutrophil/lymphocyte ratio (NLR) in patients with type 2 diabetes mellitus (T2DM), to compare with non-diabetics and to establish its correlation with the concentration of ultrasensitive C-reactive protein in a population of the town of Riobamba, Ecuador. Materials and methods: a descriptive, correlational, crosssectional, research was conducted from July 2019 to February 2020. Eighty individuals were selected to participate in the project, 25 control subjects and 55 patients with a diagnosis of T2DM. Each subject had a fasting blood sample drawn for the determination of glucose, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, ultrasensitive C-reactive protein (hs-CRP), glycosylated hemoglobin (HbA1c), total leukocyte count, neutrophils and lymphocytes. Results: a significant increase in glucose concentration (p<0.0001), HbA1c (p<0.0001), body mass index (BMI) (p<0.0001), hs-CRP (p<0.0001), absolute neutrophil count (p=0.001), absolute lymphocyte count (p=0.04), and NLR (p=0.0005), and a significant reduction in HDL cholesterol (p=0.02), were found in patients with T2DM vs controls. A positive correlation (p<0.0001; r=0.7774) was observed between NLR and hs-CRP in patients with T2DM. Conclusions: patients with T2DM experience elevation in NLR which correlates with increase in hs-CRP concentration.

Importancia del índice neutrófilo-linfocito en su asociación con mortalidad en pacientes con COVID-19: Experiencia en un centro de salud en Argentina / Importance of the neutrophil-lymphocyte ratio in its association with mortality in patients with COVID-19: Experience in a health center in Argentina

ANTECEDENTES: El COVID-19 presenta una progresión a cuadros respiratorios graves que pueden culminar con la muerte. Al ser una pandemia, hay necesidad de herramientas de bajo costo que permitan determinar su evolución. El índice neutrófilo-linfocito (INL) es un marcador inflamatorio estudiado en diversas patologías. OBJETIVO: Estimar la asociación entre INL > 3 y mortalidad en pacientes hospitalizados con COVID 19. PACIENTES Y MÉTODOS: Se incluyeron pacientes con diagnóstico de COVID 19 que ingresaron a la sala de internación general de nuestro hospital, desde marzo hasta agosto de 2020. Los pacientes se dividieron en dos grupos: con INL 3. Se realizó un modelo de regresión logística múltiple para estimar la asociación entre el INL > 3 y mortalidad. RESULTADOS: Se incluyeron 711 pacientes con COVID-19. El modelo de regresión logística múltiple mostró asociación entre INL > 3 y mortalidad (OR 3.8; IC95% 1,05 a 13,7; p 0,04) ajustado por edad, días de internación, traslados a terapia intensiva, neumonía grave, valores de proteína-C-reactiva, hipertensión arterial, y comorbilidad neurológica, renal crónica, cardiaca y oncológica previas. COCLUSIÓN: El INL es accesible en la evaluación inicial de los pacientes que se internan con COVID-19, habiéndose asociado en nuestra serie con mortalidad.

BACKGROUND: COVID-19 rapidly progresses to acute respiratory failure and mortality. A pandemic needs an urgent requirement for low-cost and easy-access tools that assess the infection evolution. The neutrophil-lymphocyte ratio (NLR) is an inflammatory biomarker used in several diseases. AIM: To estimate the association between NLR > 3 with mortality in hospitalized patients with COVID 19. METHODS: NLR was analyzed in patients with COVID-19 seen at Hospital Fernandez between March and August 2020. Patients were grouped in those with NLR 3. Clinical characteristics and mortality were analyzed and compared between groups. A multivariable regression model was used to estimate the association between NLR > 3 and mortality. RESULTS: We included 711 patients with COVID-19. In a multivariable regression model, NLR > 3 associated with mortality (OR 3.8; 95% CI 1.05 to 13.7; p 0.04) adjusting by age, days of hospitalization, intensive care requirement, severe pneumonia, C-reactive protein levels, arterial hypertension, and comorbidities. CONCLUSION: NLR was associated with mortality, and it is an accessible and easy tool to use in the first evaluation of hospitalized patients with COVID-19.

Anticuerpos contra el citoplasma del neutrófilo y actividad clínica en pacientes cubanos con artritis reumatoide / Antineutrophil cytoplasmic autoantibodies and clinical activity in Cuban patients with rheumatoid arthritis

Introducción: Los anticuerpos contra el citoplasma del neutrófilo se detectan normalmente en pacientes con vasculitis. Aunque estos anticuerpos pueden estar presentes en un amplio número de enfermedades asociadas a estados inflamatorios y autoinmunes, como la artritis reumatoide, no se ha demostrado su significado clínico. Objetivo: evaluar la utilidad de diferentes especificidades antigénicas de los anticuerpos contra el citoplasma del neutrófilo para medir la actividad clínica en pacientes cubanos con artritis reumatoide. Material y Métodos: Se realizó un estudio transversal con 77 pacientes cubanos con artritis reumatoide. Se determinaron la velocidad de sedimentación globular, la proteína C reactiva, el indicador clínico de actividad de la enfermedad, los anticuerpos anti-proteínas citrulinadas, el factor reumatoide y los anticuerpos contra el citoplasma del neutrófilo frente a diferentes especificidades antigénicas. Resultados: La mayor cantidad de pacientes con actividad clínica elevada (> 5,1) pertenecieron al grupo de pacientes positivos de anticuerpos contra el citoplasma del neutrófilo (p=0,0364). Los pacientes con anticuerpos anti-lactoferrina tuvieron mayores valores de actividad clínica (p=0,0304). Mediante análisis multivariado se demostró la influencia de la positividad de anticuerpos anti-lisozima (p=0,0391), de la positividad doble de los anticuerpos anti-proteínas citrulinadas y anti-lactoferrina (p=0,0282), así como de la doble positividad de los anticuerpos anti-proteínas citrulinadas y anti-elastina (p=0,0182) en la actividad clínica. Conclusión: La presencia de anticuerpos contra el citoplasma del neutrófilo que reconocen las especificidades antigénicas lisozima, lactoferrina y elastina se relacionan con mayor actividad clínica en pacientes con artritis reumatoide(AU)

Introduction: Antibodies against neutrophil cytoplasm are normally detected in patients with vasculitis. Although these antibodies can be present in a wide number of diseases associated with inflammatory and autoimmune conditions such as rheumatoid arthritis, their clinical significance has not been demonstrated. Objective: To evaluate the usefulness of different antigenic specificities of antibodies against neutrophil cytoplasm to measure the clinical activity in Cuban patients with rheumatoid arthritis. Material and Methods: A cross-sectional study was conducted on 77 Cuban patients with rheumatoid arthritis. Erythrocyte sedimentation rate, C-reactive protein, the clinical indicator of disease activity, anti-citrullinated protein antibodies, rheumatoid factor, and antibodies against neutrophil cytoplasm against different specificities were determined. Results: The largest number of patients with elevated disease activity (> 5.1) belonged to the group of antibodies against neutrophil cytoplasm positive patients (p=0.0364). Patients with anti-lactoferrin antibodies had higher disease activity values ​​(p=0.0304). Through multivariate analysis, the influence of positive anti-lysozyme antibodies (p=0.0391), of double positivity of anti-citrullinated protein and anti-lactoferrin antibodies (p=0.0282), as well as that of double positivity of anti-citrullinated protein and anti-elastin antibodies (p=0.0182) on disease activity were demonstrated. Conclusion: The antibodies against neutrophil cytoplasm that recognize the antigenic specificities of lysozyme, lactoferrin and elastin are related to higher clinical activity in patients with rheumatoid arthritis(AU)

Evolución clínica de pacientes internados con cáncer e infección por COVID-19 / Clinical outcomes in cancer patients hospitalized with COVID-19

Resumen Los pacientes con cáncer y COVID-19 tienen más complicaciones que la población general. Comunicamos una cohorte de 74 pacientes con cáncer y COVID-19 internados en una institución on cológica. El 87.8% tenía diagnóstico de tumores sólidos y 12.2% oncohematológicos. Entre los tumores sólidos, el 61.5% presentó enfermedad metastásica. El 78.3% (N = 58) tenía infiltrados pulmonares al diagnóstico de COVID-19. La infección fue intrahospitalaria en 20 pacientes. Habían recibido tratamiento antineoplásico den tro de los 30 días anteriores al diagnóstico 39 pacientes (52.7%); uno se encontraba recibiendo radioterapia. Veinticuatro pacientes (32.4%) se derivaron a terapia intensiva (UTI) y 18 (75%) de ellos requirieron asistencia respiratoria mecánica (ARM). La mortalidad general durante la internación fue 32.4% (N = 24). La mortalidad en UTI fue 62.5% (N = 15). La mortalidad en ARM fue 72.2% (N = 13). La edad, recuento de neutrófilos, índice neutrófilo/linfocito, dímero D, ferritina, tabaquismo y haber adquirido la infección durante la internación resultaron estadísticamente significativos en el análisis univariado para mortalidad. No hallamos diferencias en mortalidad por estadio de enfermedad, en los pacientes con tumores sólidos, ni por haber recibido tratamiento antineoplá sico dentro de los 30 días del diagnóstico de COVID-19. En el análisis multivariado con el modelo de regresión logística, solo la edad y el tabaquismo fueron predictores de mortalidad. Los odds ratios (IC 95) ajustados para la edad ≥65 años y el tabaquismo fueron 8.87 (1.35-58.02) y 8.64 (1.32-56.64), respectivamente. Este trabajo puede resultar de utilidad para instituciones polivalentes que asistan pacientes oncológicos durante la pandemia.

Abstract Cancer patients are exposed to more complications from COVID-19 than non-cancer patients. We report a cohort of 74 cancer patients (87.8% with solid neoplasia and 12.2% with hematological diseases) with COVID-19 infection admitted to a tertiary medical cancer center in Argentina. Pulmonary infiltrates were diagnosed at admission in 78.3% (N = 58) of the cases. COVID-19 infection was hospital-acquired in 20 (27.0%) patients. Thirty-nine patients (52.7%) received anticancer therapy within the 30 days prior to COVID-19 diagnosis; one was on radiation therapy. Twenty-four (32.4%) patients were admitted in the intensive care unit (ICU) and 18 (75.0%) required mechanical ventilation. All cause in-hospital mortality was 32.4% (N = 24) and ICU mortality was 62.5% (N = 15). Mortality under me chanical ventilation was 72.2% (N = 13). In the univariate analysis age, neutrophil count, neutrophil/lymphocyte index, D-dimer, ferritin, smoking, and nosocomial acquired infection were associated with in-hospital mortality. There were no statistically significant differences in mortality related to disease stage for solid tumors, neither cancer treatment within 30 days of COVID-19 diagnosis. Age and smoking were associated with mortality in the multivariate analysis. The adjusted odds ratios (95 CI) for age ≥ 65 years and smoking were 8.87 (1.35-58.02) and 8.64 (1.32 - 56.64), respectively. Our experience can be useful for other institutions that assist cancer patients during the pandemic.

Índice neutrófilo linfocitario en la predicción del infarto del miocardio tipo 4a / Lymphocyte neutrophilic index in the prediction of type 4 myocardial infarction

Introducción: El infarto del miocardio tipo 4a es una complicación del intervencionismo coronario percutáneo, que se asocia a un proceso inflamatorio. El índice neutrófilo linfocitario, como marcador de inflamación, pudiera incluirse en su estratificación del riesgo. Objetivos: Evaluar la sensibilidad, especificidad, los valores predictivos y la variación del índice neutrófilo linfocitario en la predicción del infarto del miocardio tipo 4a. Métodos: Investigación de cohorte prospectiva, en 184 pacientes a los que se les realizó intervencionismo coronario percutáneo. Resultados: Para un valor mayor e igual a 2,74, el índice mostró una sensibilidad de 72,0 por ciento, una especificidad de 74,8 por ciento un valor predictivo negativo de 94,4 por ciento en la predicción de infarto tipo 4a. La variación del índice fue predictor independiente de la complicación p < 0,001. Conclusiones: El índice neutrófilo linfocitario tiene alta sensibilidad, especificidad y valor predictivo negativo en la predicción del infarto tipo 4a. Su elevación a las seis horas del proceder es un predictor independiente para dicha complicación(AU)

Introduction: Type 4a myocardial infarction is a complication of percutaneous coronary intervention, which is associated with an inflammatory process. The lymphocyte neutrophilic index, as a marker of inflammation, could be included in your risk stratification. Objectives: To assess the sensitivity, specificity, predictive values and the variation of the lymphocyte neutrophilic index in the prediction of type 4a myocardial infarction. Methods: A prospective cohort investigation was carried in 184 patients who underwent percutaneous coronary intervention. Results: For a value higher than and equal to 2.74, the index showed 72.0 percent, sensitivity, 74.8 percent specificity and 94.4 percent negative predictive value in the prediction of type 4a infarction. The variation of the index was an independent predictor of the complication p < 0.001. Conclusions: The lymphocyte neutrophil index has high sensitivity, specificity and negative predictive value in the prediction of type 4a infarction. Its elevation six hours after the procedure is an independent predictor for this complication(AU)

Detection of Leishmania infantum amastigotes in neutrophil from peripheral blood in a naturally infected dog / Detecção de formas amastigotas de Leishmania infantum em neutrófilos do sangue periférico de cão naturalmente infectado

Abstract Canine visceral leishmaniasis (CVL) is a zoonotic disease of high lethality caused by Leishmania infantum in the Americas. In the infected dog, the amastigotes are scarce in blood, especially in the late phase of the disease. This study aimed to report a rare case of L. infantum amastigotes found in neutrophils from peripheral blood of a naturally infected dog in terminal phase of CVL, also describing its clinical status before and after treatment with miltefosine 2%. The dog, which presented as polysymptomatic and with classical signs and symptoms of CVL was submitted to the following tests: Dual Path Platform (DPP) rapid test, ELISA and parasitological examination of peripheral blood. Hematological and biochemical parameters were obtained before and after treatment. All diagnostic tests were positive for CVL. The identification of L. infantum amastigotes inside neutrophils from peripheral blood was confirmed through microscopy, and the species was confirmed by molecular analysis. At the end of the treatment, peripheral parasitemia was not detected, and improvements were observed in clinical and laboratorial parameters. Finally, this atypical finding can be used as example to raise discussions about the real immunological role of neutrophils in late phases of CVL and its clinical/therapeutic implications.

Resumo A leishmaniose visceral canina (LVC) é uma doença zoonótica de alta letalidade causada por Leishmania infantum nas Américas. No cão infectado, as formas amastigotas são escassas no sangue, principalmente na fase tardia da doença. Este estudo teve como objetivo relatar um caso raro de amastigotas de L. infantum encontradas em neutrófilos do sangue periférico de um cão naturalmente infectado e terminal da LVC, descrevendo também seu estado clínico antes e após o tratamento com miltefosina a 2%. O cão, que se apresentou como polissintomático e com sinais e sintomas clássicos da LVC foi submetido aos seguintes testes: teste rápido Dual Path Platform (DPP), ELISA e exame parasitológico de sangue periférico. Os parâmetros hematológicos e bioquímicos foram obtidos antes e após o tratamento. Todos os testes diagnósticos foram positivos para LVC. A identificação de formas amastigotas de L. infantum, dentro de neutrófilos do sangue periférico foi confirmada por microscopia, e a espécie foi confirmada por análise molecular. Ao final do tratamento, não foi detectada parasitemia periférica, observando-se melhora dos parâmetros clínicos e laboratoriais. Por fim, esse achado atípico pode ser usado como exemplo para levantar discussões sobre o real papel imunológico dos neutrófilos nas fases tardias da LVC e suas implicações clínicas/terapêuticas.

Nanogels as prospective Biomaterial: Radio-induced Synthesis, Characterization, and Biological Assays / Los nanogeles como biomateriales prospectivos: síntesis radioinducida, caracterización y ensayos biológicos

Nowadays, there is a growing interest in biodegradable polymers-based materials due to their diverse application in the biomedical field. Most studied systems involve biocompatible micro and nanodevices, such as liposomes, dendrimer, micelles or polymeric nanogels. The use of Radiation Technology, specifically gamma radiation, to produce micro and nanogels raises the possibility to obtain higher purity products, an important feature for biomedical and pharmaceutical applications. The radio-induced synthesis, characterization, cytotoxicity evaluation, and immunological response of nanogels are described in this study. Nanogel synthesis was performed in the absence of oxygen using aqueous polyvinylpyrrolidone solutions. Crosslinking reactions were carried out at 25 °C in a gamma irradiation chamber with a 60Co source. Nanogels properties were analysed by Scanning Electron Microscopy, Attenuated Total Reflection-Fourier Transform Spectroscopy, Dynamic Light Scattering, and Viscosimetry. The cytotoxicity and immunological response were evaluated by MTT test and analysis of the neutrophil respiratory burst. The results showed that nanogels formation strongly depends on the total absorbed dose. The nanogels have an elliptical shape and their chemical structure is similar to the initial polymer. The nanogels are biocompatible and promote a low-intensity neutrophil activation, similar to the well-characterized biomaterial TiO2, suggesting their potential biomedical uses(AU)

En la actualidad existe un interés creciente en los materiales biodegradables basados en polímeros, debido a sus diversas aplicaciones en la esfera de la biomedicina. En la mayoría de los sistemas estudiados participan micro- y nanodispositivos biocompatibles, tales como liposomas, dendrímeros, micelas o nanogeles poliméricos. El uso de la tecnología de radiaciones, en particular de radiaciones gamma, para producir micro- y nanogeles, eleva la posibilidad de obtener productos de mayor pureza, un rasgo importante con vistas a su aplicación biomédica y farmacéutica. El estudio describe la síntesis radioinducida, caracterización, evaluación de la citotoxicidad y respuesta inmunológica de los nanogeles. La síntesis de los nanogeles se realizó en ausencia de oxígeno, usando soluciones acuosas de polivinilpirrolidona. Las reacciones de entrecruzamiento se realizaron a 25 ºC en cámara de irradiación gamma con una fuente de 60Co. Las propiedades de los nanogeles se analizaron mediante microscopía electrónica de barrido, espectroscopia por transformada de Fourier total atenuada, dispersión dinámica de luz y viscosimetría. La citotoxicidad y la respuesta inmunológica se evaluaron mediante prueba MTT y análisis del estallido respiratorio de neutrófilos. Los resultados muestran que la formación de nanogeles depende en gran medida de la dosis total absorbida. Los nanogeles tienen forma elíptica y su estructura química es similar a la del polímero inicial. Los nanogeles son biocompatibles y promueven una activación de neutrófilos de baja intensidad similar al bien caracterizado material TiO2, lo que sugiere usos biomédicos potenciales(AU)

Indicadores de valor pronóstico de amputación en pacientes hospitalizados con pie diabético / Indicators of amputation´s prognostic value in hospitalized patients with diabetic foot

Introducción: La diabetes mellitus es la causa más importante de amputaciones no traumáticas en el mundo. El pronóstico de riesgo de amputación resulta vital para el tratamiento óptimo de los pacientes hospitalizados con pie diabético. Objetivo: Caracterizar las variables con valor pronóstico de amputación en pacientes hospitalizados con diagnóstico de pie diabético. Método: Se realizó un estudio analítico longitudinal prospectivo en el período desde diciembre de 2015 hasta diciembre de 2017, con una muestra constituida por 77 pacientes. Las variables recogidas fueron edad, sexo, resultados hemoquímicos al ingreso, co-morbilidad, control glucémico y amputaciones realizadas, estos dos últimos durante la estadía hospitalaria. Se hizo inclusión de las variables con asociación significativa en un análisis univariado (p < 0,05) en un modelo de regresión logística múltiple para evaluar su asociación independiente. Se determinaron los valores predictivos positivos, negativos, y el grado de sensibilidad y especificidad. Resultados: Los indicadores pronósticos resultantes del análisis de las variables fueron el índice leuco-hematocrito (p = 0,045), el nivel de albúmina en sangre (p = 0,004), la glicemia a mitad del ingreso (p = 0,045) y la glicemia al ingreso (p = 0,039). El índice leuco-hematocrito, menor de 6 al ingreso, se relacionó con una especificidad de 92 por ciento; la albúmina, menor de 29,9 g/L, presentó un valor predictivo positivo de 71 por ciento; la glicemia al ingreso, mayor de 21,5 mmol/L, mostró una sensibilidad de 75 por ciento; y la glicemia a mitad del ingreso, mayor de 12,9 mmol/L, manifestó una sensibilidad de 71 por ciento. Conclusiones: La evolución a la amputación de los pacientes ingresados por pie diabético se relaciona con el estado inflamatorio crónico, el estado nutricional y el control glucémico(AU)

Introduction: Diabetes mellitus is the most important cause of non-traumatic amputations in the world. The prognosis of amputation risk is vital for the optimal treatment of patients hospitalized with diabetic foot disease. Objective: Characterize variables with amputation´s prognostic value in hospitalized patients diagnosed with diabetic foot disease. Method: A prospective longitudinal analytical study was conducted in the period from December 2015 to December 2017, with a sample consisting of 77 patients. The variables collected were age, sex, hemochemical results upon admission, co-morbidity, glycaemic control and amputations performed, the latter two during the hospital stay. Variables with significant association were included in a one-variety analysis (p < 0.05) in a multiple logistic regression model to evaluate their independent association. Positive, negative predictive values, and the degree of sensitivity and specificity were determined. Results: The prognosis indicators resulting from the analysis of the variables were the leuko-hematocrit index (p = 0.045), the level of albumin in blood (p = 0.004), the glycaemia at the mid-time of the stay (p = 0.045) and the glycaemia at the admission time (p = 0.039). The leuko-hematocrit index, in less than 6 patients at admission time, was related to a specificity of 92 percent; albumin, in less than 29.9 g/L, had a positive predictive value of 71 percent; glycaemia at admission time, higher than 21.5 mmol/L, showed a sensitivity of 75 percent;and glycaemia at mid-time of the stay, higher than 12.9 mmol/L, showed a sensitivity of 71 percent. Conclusions: The evolution to amputation of patients admitted due to diabetic foot is related to chronic inflammatory state, nutritional state and glycaemic control(AU)

Asociación entre los niveles séricos de vitamina D y marcadores inflamatorios en pacientes en hemodiálisis / Association between vitamin D serum levels and inflammatory markers in patients on hemodialysis

Resumen Introducción: La relación entre 25-OH-vitamina D y el sistema inmune en pacientes con enfermedad renal crónica es objeto de atención. Objetivos: Evaluar la prevalencia de la deficiencia de vitamina D en pacientes en hemodiálisis e investigar la asociación entre la vitamina D y proteína C reactiva ultrasensible (PCRus), índice neutrófilo/linfocito (INL) e índice plaqueta/linfocito (IPL). Método: Estudio transversal de 80 pacientes en hemodiálisis, divididos en dos grupos: un nivel sérico de 25-OH-vitamina D < 20 ng/mL se consideró como deficiencia de vitamina D y ≥ 20 ng/mL, como normal. Con el análisis de correlación de Spearman se definió la relación entre los parámetros. Resultados: 40 % de los pacientes presentó deficiencia de vitamina D. Hubo diferencias significativas entre los grupos en PCRus (p = 0.047), INL (p = 0.039), IPL (p = 0.042) y tratamiento con análogos de vitamina D (p = 0.022). La vitamina D tuvo una correlación negativa significativa con PCRus (p = 0.026), INL (p = 0.013) e IPL (p = 0.022). Conclusiones: La deficiencia de vitamina D fue de 40 %. Los niveles de PCRus, INL e IPL fueron significativamente más altos ante deficiencia de vitamina D. Se encontró correlación inversa significativa entre vitamina D y PCRus, INL e IPL.

Abstract Introduction: The relationship between 25-OH-vitamin D and the immune system in patients with chronic kidney disease is a subject of attention. Objectives: To assess the prevalence of vitamin D deficiency in patients on hemodialysis and to investigate the association between vitamin D, ultra-sensitive C-reactive protein (US-CRP), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Method: Cross-sectional study of 80 patients on hemodialysis, divided into two groups: a serum 25-OH-vitamin D level < 20 ng/mL was considered to be vitamin D deficiency and a serum level ≥ 20 ng/mL was regarded as normal. The relationship between the parameters was defined with Spearman’s correlation analysis. Results: 40 % of the patients had vitamin D deficiency. There were significant differences between groups in US-CRP (p = 0.047), NLR (p = 0.039), PLR (p = 0.042) and treatment with vitamin D analogues (p = 0.022). Vitamin D had a significant negative correlation with US-CRP (p = 0.026), NLR (p = 0.013) and PLR (p = 0.022). Conclusions: The prevalence of vitamin D deficiency was 40 %. The values of US-CRP, NLR and PLR were significantly higher in the presence of vitamin D deficiency. A significant inverse correlation was found between vitamin D levels and US-CRP, NLR and PLR.

Índices neutrófilo/linfocito, plaqueta/linfocito e inmunidad/inflamación sistémica en pacientes con neumonía por COVID-19 / Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index in patients with COVID-19-associated pneumonia

Resumen Introducción: Existen índices hematológicos que correlacionan la severidad y predicen la mortalidad, principalmente en estados sépticos y de inflamación. Objetivo: Correlacionar los índices neutrófilo/linfocito (INL), plaqueta/linfocito (IPL) e inmunidad/inflamación sistémica (IIIS) con la severidad de COVID-19. Método: Estudio descriptivo, analítico y retrospectivo de pacientes con neumonía por COVID-19, en quienes se analizaron INL, IPL e IIIS. Resultados: Se incluyeron 100 pacientes, 54 hombres y 46 mujeres, con una media de 49.4 ± 19.3 años. Las medias de INL, IPL e IIIS fueron 10.7 ± 10.9, 290.1 ± 229.2 y 2.6 ± 3.4 × 109, respectivamente. En 54 %, la neumonía fue leve y en 46 %, grave. En cuanto a los desenlaces hospitalarios, 75 % egresó por mejoría y 25 % falleció. Las medias de INL, IPL e IIIS de los pacientes que fallecieron versus las de los pacientes que mejoraron fueron 20.4 ± 16.9 versus 7.5 ± 4.9 (p = 0.001), 417.1 ± 379.7 versus 247.7 ± 127.4 (p = 0.038) y 4.8 ± 6.1 versus 1.9 ± 1.2 × 109 (p = 0.030), respectivamente. Conclusión: Los índices hematológicos en pacientes con neumonía por COVID-19 pueden ser empleados como predictores de severidad y pronóstico.

Abstract Introduction: There are hematological parameters that correlate severity and predict mortality mainly in septic and inflammatory states. Objective: To correlate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) with COVID-19 severity. Method: Descriptive, analytical, retrospective study of patients with COVID-19 pneumonia, in which NLR, PLR and SII were analyzed. Results: One-hundred patients were included, 54 men and 46 women, with a mean age of 49.4 ± 19.3 years. NLR, PLR and SII means were 10.7 ± 10.9, 290.1 ± 229.2, and 2.6 ± 3.4 × 109, respectively. In 54 %, pneumonia was mild, and in 46 %, severe. Regarding hospital outcomes, 75 % were discharged due to improvement and 25 % died. NLR, PLR and SII means of the patients who died versus the patients who improved were 20.4 ± 16.9 versus 7.5 ± 4.9 (p = 0.001), 417.1 ± 379.7 versus 247.7 ± 127.4 (p = 0.038) and 4.8 ± 6.1 versus 1.9 ± 1.2 × 109 (p = 0.030), respectively. Conclusion: Hematological parameters can be used in patients with COVID-19-associated pneumonia as predictors of severity and prognosis.