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.

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.

Predictive value of neutrophil-lymphocyte ratio for long-term cardiovascular event following coronary artery bypass grafting

Abstract Objective: To investigate the predictive value of preoperative neutrophil-lymphocyte ratio (NLR) for long-term major adverse cardiac and cerebrovascular events (MACCE), which have not yet been well described, in patients undergoing coronary artery bypass grafting (CABG). Methods: The records of 751 consecutive patients who underwent elective CABG between January 2008 and January 2010 were retrospectively enrolled and stratified according to quartiles of preoperative NLR. At 7.8-year follow-up, MACCE was considered as an endpoint. Results: Overall MACCE was 11.6% of all cases. Long-term myocardial infarction, percutaneous coronary intervention, stroke and cardiovascular mortality were found associated with the upper NLR quartile (P<0.001, P<0.001, P=0.005, P<0.001, respectively). In multivariate analysis, NLR on admission remained an independent predictor of long-term MACCE (OR 1.087, 95% CI 1.026-1.151; P=0.004), in all EuroSCORE risk groups (P<0.001; P<0.001; P=0.029). The receiver operating characteristic (ROC) curve analyses revealed an NLR cut-off value of 4.32 predicting MACCE. Conclusion: NLR is a useful and readily available predictive marker of long-term MACCE following CABG, independent of the EuroSCORE.

Is neutrophil to lymphocyte ratio a predictive factor for recurrence of urethral stricture?

SUMMARY INTRODUCTION Due to spongiofibrosis and inflammatory processes underlying the pathogenesis of urethral stricture, it is possible that the neutrophil-lymphocyte ratio (NLR) may give essential information about the course of the disease and recurrence possibilities. Our study aims to evaluate the correlation between NLR and recurrence rates. METHODS A total of 512 patients who underwent direct visual internal urethrotomy (DVIU) due to urethral stricture in our clinic between February 2010 and January 2018 were evaluated retrospectively. RESULTS The median follow up for non-recurrent and recurrent groups after DVIU was 30 and 36 months, respectively. During the follow-up, 280 (54.7%) of the patients had recurrences, and 232 (45,3%) had no recurrences. The mean time for recurrence after DVIU was 6,5±1,4 months, with a range of 1-36 months. The mean NLR in the non-recurrence group was 2,02±0,87, with a median of 1.9, and 3,66±2,30, with a median of 3 in the recurrence group. A highly significant statistical difference was observed between two groups in terms of neutrophil count and NLR (p: 0.000 - both). The area under curve value for NLR was 0.767, with a standard error of 0.021 (95% CI 0.727-0.808). The cut-off value of NLR was determined as 2.25, with a 70% sensitivity and 67,7% specificity. CONCLUSION By using NLR, the inflammatory features of the urethral tissue can be predicted, and possible recurrences after surgery can be estimated. Consequently, open urethroplasty techniques can be used in cases with a significant NLR value instead of the recurrent endoscopic procedure.

RESUMO INTRODUÇÃO Devido à espongiofibrose e processos inflamatórios subjacentes à patogênese da estenose uretral, pode-se pensar que a relação de linfócitos neutrofílicos (NLR) pode fornecer informações essenciais sobre o curso da doença e as possibilidades de recorrência. O objetivo do nosso estudo é avaliar a correlação entre NLR e taxas de recorrência. MÉTODOS Quinhentos e doze pacientes submetidos à uretrotomia interna visual direta (DVIU) devido à estenose uretral em nossa clínica entre as datas de fevereiro de 2010 e janeiro de 2018 foram avaliados retrospectivamente. RESULTADOS A mediana de acompanhamento para os grupos não recorrentes e recorrentes após a DVIU foi de 30 e 36 meses, respectivamente. Durante o seguimento, 280 (54,7%) dos pacientes tiveram recidivas e 232 (45,3%) não tiveram recidivas. O tempo médio de recorrência após a DVIU foi de 6,5±1,4 mês, com variação de 1-36 meses. A média da RNL no grupo sem recorrência foi de 2,02±0,87 com mediana de 1,9 e 3,66±2,30 com mediana de 3 no grupo com recidiva. Uma diferença estatística altamente significativa foi observada entre dois grupos em termos de contagem de neutrófilos e NLR (p: 0,000 - ambos). A área sob o valor da curva para NLR foi de 0,767 com um erro padrão de 0,021 (IC 95% 0,727-0,808). Valor de corte de NLR determinado como 2,25 com uma sensibilidade de 70%, especificidade de 67,7%. CONCLUSÃO Ao utilizar a RNL, as características inflamatórias do tecido uretral podem ser previstas e possíveis recidivas após a cirurgia podem ser estimadas. Dessa forma, técnicas de uretroplastia aberta podem ser usadas em casos com valor significativo de NLR em vez de procedimento endoscópico recorrente.

Platelet to lymphocyte and neutrophil to lymphocyte ratios as strong predictors of mortality in intensive care population

SUMMARY OBJECTIVE: Patients in intensive care units (ICU) have greater morbidity and mortality. We aimed to study neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in the ICU population. METHODS: Medical and laboratory data of patients treated in ICU were retrospectively analyzed. Patients were divided into deceased and survived groups. RESULTS: The NLR of survived and deceased groups were 3.6 (0.2-31) and 9.5 (1-40), respectively (p<0.001). The PLR of the survived group (111 [16-537]) was significantly lower than the PLR of the deceased (209 [52-1143]), (p<0.001). An NLR higher than 4.9 had 84% sensitivity and 67% specificity is selecting deceased patients (AUC:0.80, p<0.001). A PLR higher than 112 had 83% sensitivity and 52% specificity in predicting deadly cases (AUC:0.76, p<0.001). Both PLR and NLR were significantly and positively correlated with c reactive protein levels. CONCLUSION: We suggest that physicians should pay particular attention to the treatment of patients in ICU with elevated NLR and PLR.

RESUMO OBJETIVO: Pacientes em unidades de terapia intensiva (UTI) apresentam maior morbimortalidade. Nosso objetivo foi estudar a razão de neutrófilos para linfócitos (NLR) e de plaquetas para linfócitos (PLR) na população de UTI. MÉTODOS: Dados médicos e laboratoriais dos pacientes tratados em UTI foram analisados retrospectivamente. Os pacientes foram divididos em grupos de falecidos e de sobreviventes. RESULTADOS: O NLR de indivíduos sobreviventes e falecidos foi de 3,6 (0,2-31) e 9,5 (1-40), respectivamente (p < 0,001). A PLR dos pacientes sobreviventes (111 [16-537]) foi significativamente menor do que a PLR do grupo dos falecidos (209 [52-1143]), (p < 0,001). Uma RNL maior que 4,9 teve 84% de sensibilidade e 67% de especificidade na previsão de casos mortais. (AUC: 0,80, p < 0,001). Uma PLR superior a 112 apresentou sensibilidade de 83% e especificidade de 52% na previsão de casos mortais (AUC: 0,76, p <0,001). Ambos, PLR e NLR, foram significativamente e positivamente correlacionados com os níveis de proteína reativa c. CONCLUSÃO: Sugerimos que os médicos prestem atenção especial ao tratamento de pacientes em UTI com valores elevados de RNL e RPL.

Razão neutrófilo-linfócito no diagnóstico precoce de sepse em unidade de terapia intensiva: um estudo de caso-controle / Neutrophil-lymphocyte ratio in the early diagnosis of sepsis in an intensive care unit: a case-control study

RESUMO Objetivo: Avaliar a razão neutrófilo-linfócito na predição de sepse e mortalidade em pacientes admitidos em uma unidade de terapia intensiva. Métodos: Estudo de caso-controle de pacientes adultos admitidos em terapia intensiva. Foram incluídos como casos pacientes que tiveram sepse como razão de admissão e possuíam exame laboratorial de hemograma prévio. As análises estatísticas realizadas foram curva ROC, regressão logística binária, Mann Whitney e qui-quadrado de Pearson. Foi considerado significativo valor de p < 0,05. Resultados: Os valores de curva ROC foram 0,62 para razão neutrófilo-linfócito, 0,98 para neutrófilos bastonados e 0,51 para leucócitos totais. A presença de razão neutrófilo-linfócito superior a 5,0, o número de leucócitos acima de 12.000mm3/mL e número de neutrófilos bastonados acima 10% foram fatores de risco para sepse, entretanto somente os escores SAPS 3 e SOFA estavam relacionados a mortalidade dos pacientes. Conclusão: A razão neutrófilo-linfócito e os neutrófilos bastonados em combinação com outros parâmetros podem ser marcadores na detecção precoce de sepse em terapia intensiva.

ABSTRACT Objective: To evaluate the neutrophil-lymphocyte ratio as a predictor of sepsis and mortality in patients admitted to an intensive care unit. Methods: Case-control study of adult patients admitted to an intensive care unit. Patients who had sepsis as the reason for admission and who had a previous complete blood count examination were included as case patients. The following statistical analyses were performed: ROC curves, binary logistic regression, and Mann-Whitney and Pearson's chi-square tests. p < 0.05 was considered significant. Results: The ROC curve values were 0.62 for neutrophil-lymphocyte ratio, 0.98 for band neutrophils and 0.51 for total leukocytes. The presence of a neutrophil-lymphocyte ratio greater than 5.0, leukocyte count above 12,000mm3/mL and band neutrophil percentage above 10% were risk factors for sepsis; however, only the SAPS 3 and SOFA score were related to patient mortality. Conclusion: The neutrophil-lymphocyte ratio and band neutrophils in combination with other parameters may be markers for the early detection of sepsis in intensive care units.

Study of tissue inflammatory response in different mice strains infected by dematiaceous fungi Fonsecaea pedrosoi

Abstract: Background: Diseases caused by melanized fungi include mycetoma, chromoblastomycosis and phaeohyphomycosis. This broad clinical spectrum depends on the dynamic interactions between etiologic agent and host. The immune status of the host influences on the development of the disease, as, an exemple. phaeohyphomicosis is more frequently observed in immunocompromised patients. Objectives: Examine the histological inflammatory response induced by Fonsecaea pedrosoi in several different strains of mice (BALB/c, C57BL/6, Nude and SCID, and reconstituted Nude). Methods: Fonsecaea pedrosoi was cultivated on agar gel and a fragment of this gel was implanted subcutaneously in the abdominal region of female adult mice. After infection has been obtained, tissue fragment was studied histopathologically. Results: There were significant changes across the strains, with the nodular lesion more persistent in Nude and SCID mice, whereas in immunocompetent mice the lesion progressed to ulceration and healing. The histopathological analysis showed a significant acute inflammatory reaction which consisted mainly of neutrophils in the initial phase that was subsequently followed by a tuberculoid type granuloma in immunocompetent mice. Study limitations: There is no a suitable animal model for chromoblastomycosis. Conclusions: The neutrophilic infiltration had an important role in the containment of infection to prevent fungal spreading, including in immunodeficient mice. The fungal elimination was dependent on T lymphocytes. The re-exposure of C57BL/6 mice to Fonsecaea pedrosoi caused a delay in resolving the infection, and appearance of muriform cells, which may indicate that re-exposure to fungi, might lead to chronicity of infection.

Clinical significance and correlation of microRNA-21 expression and the neutrophil-lymphocyte ratio in patients with acute myocardial infarction

OBJECTIVES: To explore the clinical significance and correlation of microRNA-21 (miR-21) and the neutrophil-lymphocyte ratio (NLR) in patients with acute myocardial infarction (AMI). METHODS: The observation group contained 184 patients, while the control group contained 150 patients. The expression of miR-21 in the serum of each group was detected by qRT-PCR. RESULTS: A total of 184 patients and their family members were followed-up for 30 days, among which 35 patients died and 149 patients survived, resulting in a survival rate of 80.97%. According to univariate analysis, there were significant differences in age, cardiac troponin (cTn), heart rate, Killip grade, percutaneous coronary intervention (PCI) operation rate, miR-21 and NLR. In the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) values of miR-21 and NLR for the diagnosis of AMI were 0.909 and 0.868, respectively, and the area under the combined detection curve was 0.960. In the Kaplan-Meier survival analysis, the survival of patients with high miR-21 expression and NLR was significantly higher than that of patients with low miR-21 expression and NLR (p=0.027; p=0.001). The correlation showed that miR-21 expression in serum was positively correlated with the NLR in the observation group (r=0.528, p<0.05). cTn, heart rate, Killip classification, PCI operation rate, miR-21, NLR are independent risk factors for AMI. CONCLUSION: miR-21 and NLR play a role in the diagnosis of AMI and can be used as predictors for the survival of AMI.

Are pre and postoperative platelet to lymphocyte ratio and neutrophil to lymphocyte ratio associated with early postoperative aki following cabg?

Abstract Objective: In this study, we investigated the role of two of the recent biomarkers of inflammation on the development of acute kidney injury in the early postoperative period of isolated coronary artery bypass grafting. Methods: Three hundred and eleven patients, who underwent isolated coronary artery bypass grafting with cardiopulmonary bypass by the same surgery team in our clinic between May 2010 and October 2014, who had a preoperative serum creatinine level lower than 1.5 mg/dl were included in the study. These patients' records were reviewed retrospectively. The diagnosis of acute kidney injury was performed according to the Kidney Disease Improving Global Outcomes 2012 Acute Kidney Injury Guideline criteria. Patients who developed acute kidney injury in the early postoperative period were classified as Group-1 (n=62) and the patients with normal postoperative renal functions were classified as Group-2 (n=249). The demographic data, body mass index, comorbidities, hematologic/biochemical profiles, preoperative ejection fraction, blood transfusion history, and operative data of the groups were compared. Univariate analyses were performed to determine significant clinical factors, and multiple logistic regression analyses were subsequently done to determine independent predictors of acute kidney injury. Results: Sixty-two (19.9%) patients developed acute kidney injury during the first 72 hours postoperatively. Multivariate logistic regression analyses revealed preoperative increased creatinine (P=0.0001), C-reactive protein (P=0.02), neutrophil-lymphocyte ratio (P=0.04) and platelet-lymphocyte ratio (P=0.002); increased postoperative first day leukocyte count (P=0.03), C-reactive protein levels (P=0.02), neutrophil-lymphocyte ratio (P=0.002), platelet-lymphocyte ratio (P=0.01) and increased intubation time (P=0.006) as independent predictors of early postoperative acute kidney injury in patients who underwent isolated coronary artery bypass grafting. Conclusion: The preoperative and postoperative increased levels of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio which can be calculated by simple methods from routine blood analysis showed us that these parameters are independent biomarkers directly related to development of acute kidney injury in the early postoperative period.

Can neutrophil to lymphocyte ratio predict lamina propria invasion in patients with non muscle invasive bladder cancer?

ABSTRACT Objective Recent studies have demonstrated the role of systemic inflammation in the development and progression of cancer. In this study, we evaluated whether preoperatively measured neutrophil-to-lymphocyte ratio (NLR) can predict lamina propria invasion in patients with non-muscle-invasive bladder cancer (NMIBC). Material and Methods We reviewed the medical records of 304 consecutive and newly diagnosed patients with bladder cancer who had been treated with transurethral resection between January 2008 and June 2014. In total, 271 patients were included in the study and the patients were divided into two groups according to the pathological stage (Group 1: Ta, Group 2: T1). NLR was calculated by dividing the absolute neutrophil count (N) by the absolute lymphocyte count (L). Results In total, 271 patients (27 women and 244 men) were enrolled. Mean age was higher in Group 2 than in Group 1 (67.3±10.8 vs. 62.9±10.8, p<0.001). Furthermore, the presence of high grade tumors and tumors ≥3cm in size was statistically higher in Group 2 than in Group 1 (70.9% vs. 9.9%, p=0.0001; 71.8% vs. 36%, p=0.0001, respectively). While the mean white blood cell (WBC) and N counts were statistically insignificant (7.63±1.87 vs. 7.69±1.93, p=0.780; 4.72±1.54 vs. 4.46±1.38, p=0.140; respectively), L was significantly lower and NLR was significantly higher in Group 2 than in Group 1 (2.07±0.75 vs. 2.4±0.87, p=0.001; 2.62±1.5 vs. 2.19±1.62, p=0.029; respectively). Conclusion Our data indicate that high NLR and low L are statistically associated with T1 stage, whereas low L are able to predict lamina propria invasion in patients with NMIBC. These findings suggest that pretreatment measurement of NLR may provide valuable information for the clinical management of patients with NMIBC. Prospective studies are now required to further validate the role of NLR as a risk factor in NMIBC.

Clinical significance of preoperative neutrophil -to - lymphocyte ratio in renal cell carcinoma

ABSTRACT Introduction: We investigated the prognostic significance of the neutrophil-to-lymphocyte ratio on tumor stage and Fuhrman nuclear grade in renal cell carcinoma. Methods: The records of 432 patients with RCC who underwent radical or partial nephrectomy between 2005 and 2014 were retrospectively reviewed. Patients were classified as group lower tumor stage(T1 + T2) and higher(T3 + T4). As like tumor stage, Fuhrman nuclear grade were classified lower (G1+G2) and higher(G3+G4) too. The best NLR cut off value was 3.01. Two sample t-test or Mann–Whitney U-test used for the continuous variables and a chi-square test or Fisher's exact test used for the categorical variables. Results: Among the 432 total patients analyzed in our study, there were 275 males (63.7%) and 157 females (36.3%). Mean laboratory values were CRP 2.73 ± 1.93 mg/dL (normal less than 0.3), neutrophil count 4,23 ± 1.46/μL, lymphocyte count 1,61 ± 0,61/μL and NLR 2.64 ± 1.24. According to our data, statistically pretreatment NLR significantly correlated with CRP (p<0.0001). And tumor patologic stage (p=0.08), tumor histologic grade (p<0.001) was significantly associated with NLR. Discussion: We compared the relationship of preoperative NLR and NC parameters with RCC tumor stage and grade. And NLR were found to have statistically significant higher T stage and grade at RCC. Further studies with more patients are needed to confirm our study.

Inflammatory and immunological profiles in patients with COPD: relationship with FEV 1 reversibility / Perfil inflamatório e imunológico em pacientes com DPOC: relação com a reversibilidade do VEF 1

ABSTRACT Objective: To determine whether COPD severity correlates with sputum cell counts, atopy, and asthma. Methods: This was a cross-sectional study involving 37 patients with COPD and 22 healthy subjects with normal lung function (controls). Sputum cell counts were determined by microscopy after centrifugation of samples. Skin prick tests were performed, and serum cytokines were determined by ELISA. Results: Patients were stratified by bronchodilator response: a non-reversible airflow limitation (nonRAL) group comprised 24 patients showing no significant post-bronchodilator change in FEV1; and a partially reversible airflow limitation (partialRAL) group comprised 13 patients showing FEV1 reversibility (post-bronchodilator FEV1 increase ≥ 12%). The proportion of eosinophils in sputum was higher in the partialRAL group than in the nonRAL group (p < 0.01), and there was an inverse correlation between the proportion of eosinophils and FEV1 (p < 0.05). However, none of the patients had a history of asthma and skin prick test results did not differ between the two groups. In the patient sputum samples, neutrophils predominated. Serum levels of TNF, IL-6, IL-8, and RANTES (CCL5) were higher in patients than in controls (p < 0.001) but did not differ between the two patient groups. Conclusions: COPD patients with partial FEV1 reversibility appear to have higher sputum eosinophil counts and greater airway hyperresponsiveness than do those with no FEV1 reversibility. However, we found that COPD severity did not correlate with atopy or with the cytokine profile.

RESUMO Objetivo: Determinar se a gravidade da DPOC se correlaciona com a contagem de células no escarro, atopia e asma. Métodos: Estudo transversal com 37 pacientes com DPOC e 22 indivíduos saudáveis com função pulmonar normal (controles). As contagens de células no escarro foram determinadas por microscopia após a centrifugação das amostras. Foram realizados testes cutâneos de puntura, e as citocinas séricas foram determinadas por ELISA. Resultados: Os pacientes foram estratificados pela resposta ao broncodilatador: o grupo de limitação ao fluxo aéreo não reversível (LFAnr) envolveu 24 pacientes sem alteração significativa do VEF1 pós-broncodilatador, e o grupo de limitação ao fluxo aéreo parcialmente reversível (LFApr) envolveu 13 pacientes com reversibilidade do VEF1 (aumento do VEF1 pós-broncodilatador ≥ 12%). A proporção de eosinófilos no escarro foi maior no grupo LFApr do que no LFAnr (p < 0,01), e houve uma correlação inversa entre a proporção de eosinófilos e VEF1 (p < 0,05). Entretanto, nenhum dos pacientes apresentou histórico de asma e os resultados dos testes cutâneos não diferiram entre os dois grupos. Nas amostras de escarro dos pacientes, os neutrófilos predominaram. Os níveis séricos de TNF, IL-6, IL-8 e RANTES (CCL5) foram maiores nos pacientes que nos controles (p < 0,001), mas não diferiram entre os dois grupos de pacientes. Conclusões: Pacientes com DPOC e reversibilidade parcial do VEF1 parecem apresentar maiores contagens de eosinófilos no escarro e maior hiper-responsividade das vias aéreas que aqueles sem reversibilidade do VEF1. Entretanto, a gravidade da DPOC não se correlacionou com atopia ou perfil das citocinas.

Reconstitución inmune exitosa mediante trasplante de células madre hematopoyéticas en un paciente colombiano afectado con enfermedad granulomatosa crónica / Successful immune reconstitution by means of hematopoietic stem cell transplantation in a Colombian patient with chronic granulomatous disease

Introducción. La enfermedad granulomatosa crónica es una inmunodeficiencia primaria causada por mutaciones en los genes que codifican para las proteínas del sistema de la oxidasa de NADPH ( Nicotinamide Adenine Dinucleotide Phosphate ) de las células fagocíticas, las cuales afectan la producción de especies reactivas del oxígeno y la actividad microbicida. Actualmente, la única terapia curativa para esta enfermedad es la reconstitución inmune mediante el trasplante de células madre hematopoyéticas. Objetivo. Reportar la caracterización clínica y molecular de un paciente con enfermedad granulomatosa crónica ligada al cromosoma X y su reconstitución inmunitaria exitosa mediante el trasplante de células madre hematopoyéticas. Materiales y métodos. El estallido respiratorio en neutrófilos de sangre periférica se midió por citometría de flujo mediante la prueba de oxidación de la dihidrorrodamina 123 (DHR 123). El análisis de las mutaciones del gen CYBB se hizo mediante reacción en cadena de la polimerasa (PCR) en el ADN complementario y la secuenciación e hibridación genómica comparativa en el ADN genómico. En el trasplante se emplearon células madre del hermano menor con HLA idéntico, y previamente se hizo un acondicionamiento de intensidad reducida. La reconstitución inmunitaria después del trasplante se evaluó periódicamente con hemoleucogramas y la prueba DHR 123 en neutrófilos de sangre periférica. Resultados. El diagnóstico de la enfermedad granulomatosa crónica ligada al cromosoma X se estableció como resultado de una deleción hemicigota en la banda Xp21.1 que implicó la deleción completa del CYBB . La toma de injerto postrasplante para plaquetas y neutrófilos fue en los días 10 y 11, respectivamente. En el día 30 después del trasplante se logró la reconstitución hematológica completa y en los tres años siguientes no se observaron complicaciones ni infecciones. Conclusión. El trasplante de células madre hematopoyéticas permite la reconstitución completa de la función inmunitaria relacionada con la actividad microbicida de las células fagocíticas de pacientes con enfermedad granulomatosa crónica ligada al cromosoma X.

Introduction: Chronic granulomatous disease is a primary immunodeficiency that results from mutations in proteins of the NADPH oxidase system that affect the microbicidal activity of phagocytes. Immune reconstitution by hematopoietic stem cell transplantation is currently the only curative therapy for this disease. Objective: To describe the clinical and molecular characterization of a patient with X-linked chronic granulomatous disease and the successful immune reconstitution by means of a hematopoietic stem cell transplantation. Materials and methods: The respiratory burst was measured by flow cytometry using the dihydrorodamine 123 (DHR) oxidation test in neutrophils of peripheral blood. Mutational analysis of CYBB was performed by PCR amplification in complementary DNA, as well as sequencing and comparative genomic hybridization in genomic DNA. HLA-identical stem cells from the patient´s younger brother were used for the transplantation and reduced intensity pre-transplantation conditioning was administered. Post-transplantation immune reconstitution was evaluated periodically by serial complete blood counts and DHR 123 in peripheral blood neutrophils. Results: The diagnosis of X-linked chronic granulomatous disease resulted from a hemizygous deletion affecting Xp21.1 that included the entire CYBB . Post-transplantation engraftment was documented in platelets and peripheral blood neutrophils at days 10 and 11, respectively. Total hematological reconstitution was achieved by day 30 post-transplantation and no complications or infections have been observed in the three years since the transplantation. Conclusion: Hemopoietic stem cell transplantation allows for total reconstitution of the immune function related to microbicidal activity of phagocytic cells from patients with X-linked chronic granulomatous disease.

Función del sistema NADPH oxidasa en la formación de trampas extracelulares de los neutrófilos (NETs) / Role of nadph oxidase system in the neutrophil extracelular Traps (NETs) formation

Las trampas extracelulares de los neutrófilos son estructuras fundamentalmente compuestas de cromatina y proteínas granulares, que una vez liberadas constituyen un mecanismo de defensa que tiene la capacidad de atrapar y destruir microorganismos patógenos. El proceso que libera estas estructuras es conocido como NETosis y en el caso que provoque muerte celular, esta es diferente a la apoptosis y a la necrosis. Si bien no se conocen todos los eventos moleculares involucrados en la formación de las NETs, se sabe que dependiendo del estímulo, las especies reactivas del oxígeno son esenciales para que ocurra la descondensación de la cromatina y se lleve a cabo el proceso de NETosis(AU)

Neutrophil extracellular traps (NETs) are structures mainly composed of chromatin and granule proteins that once released constitute a defense mechanism due to their ability to trap and destroy pathogen microorganisms. The process by which these structures are released is known as NETosis and in case this may lead to cell death is different to apoptosis and necrosis. Although all the molecular events involved in the formation of NETs are poorly understood, it is known that depending on the stimulus, reactive oxygen species (ROS) are essential to the chromatin decondensation and subsequent NETs formation(AU)

Efectores celulares de la respuesta inflamatoria en la enfermedad pulmonar obstructiva crónica / Cellular effectors of the inflammatory response in chronic obstructive pulmonary disease (COPD)

Approximately 3 million people in the world die every year as a consequence of COPD, which is associated with an abnormal inflammatory response of the lung to noxious particles and gases. This inflammatory pattern causes pathological changes leading to a narrowing of small airways and destruction of lung parenchyma, also known as emphysema. Classically, these changes were associated to macrophages and neutrophils, although T CD8+ lymphocytes were latter added to the equation to explain the origin of emphysematous lesions. However, in recent years, multiple evidences have arisen indicating that inflammatory response in COPD is much more complex. These findings point to a key role for mast cells, dendritic cells, T CD4+ and B cells. The aim of this article is to review such evidence and report what is known so far about those cells involved in the inflammatory response in COPD.

Implicancias de la muerte del neutrófilo por NETtosis en la fisiopatogenia de la enfermedad pulmonar obstructiva crónica / Implications of the death of neutrophil by NETtosis in the pathophysiology of the disease chronic obstructive pulmonary

La enfermedad pulmonar obstructiva crónica (EPOC) incluye la bronquitis crónica y el enfisema pulmonar, es actualmente la sexta causa de muerte en todo el mundo, aunque se estima que llegará a ocupar el tercer lugar en el 20201. Constituye la quinta causa de incapacidad después de las enfermedades cardio y cerebrovasculares. La EPOC representa asimismo una significativa carga en términos de pérdidas en productividad, y los costos directos e indirectos asociados con ella podrían ser comparables a los de las enfermedades más incapacitantes como el ataque cardíaco, cáncer de pulmón o de mama

Increased neutrophil-to-lymphocyte ratio predicts persistent coronary no-flow after wire insertion in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

OBJECTIVES: Acute ST-segment elevation myocardial infarction patients presenting persistent no-flow after wire insertion have a lower survival rate despite successful mechanical intervention. The neutrophil-to-lymphocyte ratio has been associated with increased mortality and worse clinical outcomes in ST-segment elevation myocardial infarction. We hypothesized that an elevated neutrophil-to-lymphocyte ratio would also be associated with a persistent Thrombolysis In Myocardial Infarction flow grade of 0 after wire insertion in patients undergoing primary percutaneous coronary intervention. METHODS: A total of 644 patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention within 12 hours of symptom onset were included in our study. Blood samples were drawn immediately upon hospital admission. The patients were divided into 3 groups according to their Thrombolysis In Myocardial Infarction flow grade: Thrombolysis In Myocardial Infarction flow grade 0 after wire insertion, Thrombolysis In Myocardial Infarction flow grade 1-3 after wire insertion and Thrombolysis In Myocardial Infarction flow grade 1-3 at baseline. RESULTS: The neutrophil-to-lymphocyte ratio was significantly higher in the group with Thrombolysis In Myocardial Infarction flow grade 0 after wire insertion compared with the group with Thrombolysis In Myocardial Infarction flow grade 1-3 after wire insertion and the group with Thrombolysis In Myocardial Infarction flow grade 1-3 at baseline. The group with Thrombolysis In Myocardial Infarction flow grade 0 after wire insertion also had a significantly higher in-hospital mortality rate. Persistent coronary no-flow after wire insertion was independently associated with the neutrophil-to-lymphocyte ratio. CONCLUSIONS: An increased neutrophil-to-lymphocyte ratio on admission is significantly associated with persistent coronary no-flow after wire insertion in patients with ST-segment ...

Chronic granulomatous disease: why an inflammatory disease?

Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the genes encoding subunits of the phagocytic NADPH oxidase system. Patients can present with severe, recurrent infections and noninfectious conditions. Among the latter, inflammatory manifestations are predominant, especially granulomas and colitis. In this article, we systematically review the possible mechanisms of hyperinflammation in this rare primary immunodeficiency condition and their correlations with clinical aspects.

Clinical and laboratorial features of spontaneous bacterial peritonitis in southern Brazil / Características clínicas e laboratoriais da peritonite bacteriana espontânea no sul do Brasil

CONTEXT AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is a severe complication that occurs in 8-27% of hospitalized patients with liver cirrhosis and ascites, with high mortality rates. This study aimed to identify the clinical characteristics associated with SBP. DESIGN AND SETTING: Cross-sectional study, conducted in a public university. METHODS: The study consecutively included individuals with liver cirrhosis and ascites between September 2009 and March 2012. Forty-five patients were included: mean age 53.2 ± 12.3 years, 82.2% male, 73.8% Caucasian, mean Model of End-stage Liver Disease (MELD) score of 19.5 ± 7.2, and 33.3% with SBP. The subjects were divided into two groups: SBP and controls. RESULTS: Comparison between individuals with SBP and controls showed that those with SBP had lower mean prothrombin activity time (36.1 ± 16.0% versus 47.1 ± 17.2%; P = 0.044) and lower median serum-ascites albumin gradient (SAAG) (1.2 versus 1.7, P = 0.045). There was a tendency towards higher mean MELD in the SBP group, not significant (22.2 ± 7.6 versus 17.9 ± 6.7; P = 0.067). There was a strong positive correlation between the neutrophil count in ascitic fluid and serum leukocyte count (r = 0.501; P = 0.001) and a negative correlation between the neutrophil count in ascitic fluid with prothrombin activity time (r = -0.385; P = 0.011). CONCLUSION: A few characteristics are associated with the presence of SBP, especially liver dysfunction, SAAG and peripheral leukocytosis. .

CONTEXTO E OBJETIVO: Peritonite bacteriana espontânea (PBE) é uma complicação grave que ocorre em 8-27% dos pacientes hospitalizados com cirrose hepática e ascite, e apresenta altas taxas de mortalidade. O objetivo deste estudo é identificar as características clínicas associadas à PBE. TIPO DE ESTUDO E LOCAL: Estudo transversal, conduzido em uma universidade pública. MÉTODOS: O estudo incluiu, consecutivamente, indivíduos com cirrose hepática e ascite entre setembro 2009 e março 2012. Foram incluídos 45 indivíduos com média de idade de 53,2 ± 12,3 anos, sendo 82,2% homens, 73,8% brancos, com MELD (Modelo para Doença Hepática Terminal) de 19,5 ± 7,2, e 33,3% com PBE. Os indivíduos foram divididos em dois grupos: PBE e controles. RESULTADOS: Quando se compararam os indivíduos com PBE aos controles, observou-se menor média de tempo de atividade da protrombina (TAP; 36,1 ± 16,0% versus 47,1 ± 17,2%; P = 0,044) e menor mediana de gradiente albumina soro-ascite (GASA; 1,2 versus 1,7; P = 0,045). Houve tendência do grupo com PBE de apresentar maior média de MELD, sem significância estatística (22,2 ± 7,6 versus 17,9 ± 6,7; P = 0,067). Foi observada forte correlação positiva entre neutrófilos do líquido ascítico e contagem sérica de leucócitos (r = 0,501; P = 0,001) e correlação negativa de neutrófilos do líquido ascítico com TAP (r = -0,385; P = 0,011). CONCLUSÃO: Poucas características estão associadas à presença de PBE, em especial a disfunção hepática, o GASA e a leucocitose periférica. .

Evaluation of Toll-like, chemokine, and integrin receptors on monocytes and neutrophils from peripheral blood of septic patients and their correlation with clinical outcomes

Recognition of pathogens is performed by specific receptors in cells of the innate immune system, which may undergo modulation during the continuum of clinical manifestations of sepsis. Monocytes and neutrophils play a key role in host defense by sensing and destroying microorganisms. This study aimed to evaluate the expression of CD14 receptors on monocytes; CD66b and CXCR2 receptors on neutrophils; and TLR2, TLR4, TLR5, TLR9, and CD11b receptors on both cell types of septic patients. Seventy-seven septic patients (SP) and 40 healthy volunteers (HV) were included in the study, and blood samples were collected on day zero (D0) and after 7 days of therapy (D7). Evaluation of the cellular receptors was carried out by flow cytometry. Expression of CD14 on monocytes and of CD11b and CXCR2 on neutrophils from SP was lower than that from HV. Conversely, expression of TLR5 on monocytes and neutrophils was higher in SP compared with HV. Expression of TLR2 on the surface of neutrophils and that of TLR5 on monocytes and neutrophils of SP was lower at D7 than at D0. In addition, SP who survived showed reduced expression of TLR2 and TLR4 on the surface of neutrophils at D7 compared to D0. Expression of CXCR2 for surviving patients was higher at follow-up compared to baseline. We conclude that expression of recognition and cell signaling receptors is differentially regulated between SP and HV depending on the receptor being evaluated.