Capacidad pronóstica del PIV (pan-immune-inflammation value) en pacientes con carcinoma escamoso de cabeza y cuello / Prognostic capacity of PIV (pan-immune-inflammation value) in patients with head and neck squamous cell carcinoma

Introducción: El PIV (pan-immune-inflammation value), un índice que resulta del cociente (neutrófilos×monocitos×plaquetas) / linfocitos, ha sido propuesto como un biomarcador con capacidad pronóstica en diferentes modelos tumorales. El objetivo del presente estudio es analizar la capacidad pronóstica del PIV en pacientes con carcinoma escamoso de cabeza y cuello. Pacientes y métodos: Estudio retrospectivo de 1.187 pacientes con carcinoma escamoso de cabeza y cuello tratados en nuestro centro durante el periodo 2000-2017. Se obtuvo el valor del PIV a partir de un análisis realizado en un intervalo inferior a las 3 semanas previas al inicio del tratamiento. Resultados: El valor del PIV se relacionó de forma significativa con el consumo de tóxicos (p=0,001), la localización del tumor (0,0001), la extensión tumoral (0,0001), y el grado histológico (0,016). Mediante un análisis de partición recursiva se definieron 4 categorías en función del valor del PIV: categoría i: PIV<136,3 (n=118; 9,9%), categoría ii: PIV 136,3-451,1 (n=594, 50,0%); categoría iii: PIV 451,1-1.141,2 (n=357; 30,1%); categoría iv: PIV>1.141,2 (n=118; 9,9%). Se pudo observar una reducción ordenada y significativa de la supervivencia específica a medida que se incrementaba la categoría en el valor del PIV. Esta disminución en la supervivencia se produjo de forma independiente al tipo de tratamiento, la extensión del tumor, o la localización del tumor primario. La categoría en el valor del PIV se relacionó de forma significativa con la supervivencia específica en un estudio multivariable. Conclusiones: El PIV es un biomarcador con capacidad pronóstica en los pacientes con carcinoma escamoso de cabeza y cuello.(AU)

Introduction: The pan-immune-inflammation value (PIV), an index that results from the following ratio: (neutrophils×monocytes×platelets) / lymphocytes, has been proposed as a prognostic biomarker in different tumor models. The aim of this study is to analyze the prognostic capacity of PIV in patients with head and neck squamous cell carcinoma. Patients and methods: Retrospective study of 1,187 patients with head and neck squamous cell carcinoma treated at our center between 2000-2017. PIV value was obtained from an analysis performed within 3 weeks prior to the start of treatment. Results: PIV value was significantly associated with toxic consumption (0.001), tumor location (0.0001), tumor extension (0.0001), and histological grade (0.016). Four categories were defined based on PIV value using a recursive partitioning analysis: category i: PIV<136.3 (n=118, 9.9%), category ii: PIV 136.3-451.1 (n=594, 50.0%), category iii: PIV 451.1-1,141.2 (n=357, 30.1%), and category iv: PIV>1,141.2 (n=118, 9.9%). A significant and ordered decrease in disease-specific survival was observed as the PIV category increased. This decrease in survival was independent of the type of treatment, tumor extension, or location of the primary tumor. The PIV category was an independent prognostic factor of disease-specific survival in a multivariable study. Conclusions: PIV is a prognostic biomarker in patients with head and neck squamous cell carcinoma.(AU)

Prognostic performance of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio for mortality in patients with acute stroke / Rendimiento pronóstico de la razón neutrófilos/linfocitos y la razón plaquetas/linfocitos para la mortalidad en pacientes con ictus agudo

Objective: To evaluate the prognostic performance of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) for mortality in patients with acute stroke treated at a Peruvian hospital. Design: Retrospective cohort study. Setting: Tertiary care hospital. Patients: Patients aged ≥18 years with a diagnosis of acute stroke and admitted to the hospital from May 2019 to June 2021. Interventions: None. Main variables of interests: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mortality. Results: A total of 165 patients were included. The mean age was 66.1±14.2 years, and 59.4% were male. Only NLR had a performance superior to 0.7 (AUC: 0.75; 95%CI: 0.65–0.85), and its elevated levels were associated with an increased risk of mortality (aRR: 3.66; 95%CI: 1.77–8.85) after adjusting for confounders. Conclusion: The neutrophil-to-lymphocyte ratio has an acceptable prognostic performance for mortality in patients with acute stroke. Its use may be considered to stratify patients’ risk and to consider timely alternative care and management.(AU)

Objetivo: Evaluar el desempeño pronóstico de la relación neutrófilos-linfocitos (NLR) y la relación plaquetas-linfocitos (PLR) para la mortalidad en pacientes con stroke agudo tratados en un hospital peruano. Diseño: Estudio de cohorte retrospectivo. Ámbito: Hospital de atención terciaria. Participantes: Pacientes ≥18 años con diagnóstico de stroke agudo e ingresados en el hospital entre mayo de 2019 y junio de 2021. Intervenciones: Ninguna. Variables de interés principales: Razón neutrófilos/linfocitos, razón plaquetas/linfocitos y mortalidad. Resultados: Se incluyeron un total de 165 pacientes. La edad media fue de 66,1±14,2 años, y el 59,4% eran varones. Sólo el NLR tuvo un rendimiento superior a 0,7 (AUC: 0,75; IC95%: 0,65-0,85), y sus niveles elevados se asociaron con un mayor riesgo de mortalidad (RRa: 3,66; IC95%: 1,77-8,85) tras ajustar por factores de confusión. Conclusiones: La razón neutrófilos/linfocitos tiene un rendimiento pronóstico aceptable para la mortalidad en pacientes con stroke. Su uso puede ser considerado para estratificar el riesgo de los pacientes y considerar oportunamente cuidados y manejo alternativos.(AU)

LPS-TLR4 pathway exaggerates alcoholic hepatitis via provoking NETs formation / La vía LPS-TLR4 exagera la hepatitis alcohólica al provocar la formación de NET

Background Intrahepatic infiltration of neutrophils is a character of alcoholic hepatitis (AH) and neutrophil extracellular traps (NETs) are an important strategy for neutrophils to fix and kill invading microorganisms. The gut-liver axis has been thought to play a critical role in many liver diseases also including AH. However, whether NETs appear in AH and play role in AH is still unsure. Methods Serum samples from AH patients were collected and LPS and MPO-DNA were detected. WT, NE KO, and TLR4 KO mice were used to build the AH model, and the intestinal bacteria were eliminated at the same time and LPS was given. Then the formation of NETs and AH-related markers were detected. Results The serum MPO-DNA and LPS concentration was increased in AH patients and a correlation was revealed between these two indexes. More intrahepatic NETs formed in AH mice. NETs formation decreased with antibiotic intervention and restored with antibiotic intervention plus LPS supplement. While NETs formation failed to change with gut microbiome or combine LPS supplement in TLR4 KO mice. As we tested AH-related characters, liver injury, intrahepatic fat deposition, inflammation, and fibrosis alleviated with depletion of NE. These related marks were also attenuated with gut sterilization by antibiotics and recovered with a combined treatment with antibiotics plus LPS. But the AH-related markers did show a difference in TLR4 KO mice when they received the same treatment. Conclusion Intestinal-derived LPS promotes NETs formation in AH through the TLR4 pathway and further accelerates the AH process by NETs (AU)

Antecedentes La infiltración intrahepática de neutrófilos es una característica de la hepatitis alcohólica (AH, por sus siglas en inglés) y las trampas extracelulares de neutrófilos (NET, por sus siglas en inglés) son una estrategia importante para que los neutrófilos fijen y maten microorganismos invasores. Se ha pensado que el eje intestino/hígado desempeña un papel crítico en muchas enfermedades hepáticas, incluida la AH. Sin embargo, aún no está claro si las NET aparecen en la AH y desempeñan un papel en la misma. Métodos Se recogieron muestras de suero de pacientes con AH, y se detectaron LPS y MPO-ADN. Se utilizaron ratones WT, NE KO y TLR4 KO para construir el modelo de la AH, y las bacterias intestinales se eliminaron al mismo tiempo y se administró LPS. Luego se detectó la formación de NET y los marcadores relacionados con la AH. Resultados La concentración sérica de MPO-ADN y LPS aumentó en los pacientes con HA, y se reveló una correlación entre estos 2 índices. Se formaron más NET intrahepáticos en ratones con AH. La formación de las NET disminuyó con la intervención antibiótica, y se restauró con la intervención antibiótica más suplemento de LPS. Mientras que la formación de NET no pudo cambiar con el microbioma intestinal o combinar el suplemento de LPS en ratones TLR4 KO. A medida que probamos los caracteres relacionados con la AH, la lesión hepática, la deposición de grasa intrahepática, la inflamación y la fibrosis se aliviaron con el agotamiento de las NET. Estas marcas relacionadas también se atenuaron con la esterilización intestinal con antibióticos, y se recuperaron con un tratamiento combinado con antibióticos más LPS. Pero los marcadores relacionados con la AH mostraron una diferencia en los ratones TLR4 KO cuando recibieron el mismo tratamiento. Conclusión El LPS de origen intestinal promueve la formación de NET en la AH a través de la vía TLR4, y acelera aún más el proceso de AH por NET (AU)

Neutrófilos, trampas extracelulares de neutrófilos y artritis reumatoide: una revisión actualizada para clínicos / Neutrophils, neutrophil extracellular traps, and rheumatoid arthritis: An updated review for clinicians

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by the presence of autoantibodies. Research on the pathogenic mechanisms involved in systemic autoimmune diseases has largely focused on the involvement of the adaptive immune system with dysregulated responses of T and B cells. However, in recent years, there is increasing evidence of the significant role played by the innate immune system, particularly neutrophils, in these diseases, particularly in RA. Neutrophil extracellular traps (NETs) are extracellular structures composed of remodeled and concentrated chromatin with DNA, histones, and neutrophil proteins, and were first described in 2004. It has been studied that NETs may play a pathogenic role in RA and could be a source of autoantigens, increasing the immune response in the form of autoantibodies in this disease. The possible role of NETs and other markers of neutrophil activation as biomarkers of activity in RA and other immune-mediated diseases has also been studied.This article reviews the role of NETs in RA. It discusses the role of neutrophils and the latest advances in NETs, especially their involvement in autoimmune phenomena in RA. Finally, a literature review is conducted on the determination of NETs in peripheral blood and their relationship as a biomarker of RA activity, as well as their potential role in disease monitoring.(AU)

La artritis reumatoide (AR) es una enfermedad autoinmune sistémica caracterizada por la presencia de autoanticuerpos. Las investigaciones sobre los mecanismos patogénicos implicados en las enfermedades autoinmunes sistémicas se centran en gran medida en la participación del sistema inmunitario adaptativo con las respuestas desreguladas de las células T y B. Sin embargo, en los últimos años, ha aumentado la evidencia del importante papel que juega el sistema inmunitario innato, en particular los neutrófilos, en estas enfermedades, particularmente en la AR. Las trampas extracelulares de neutrófilos (NET) son estructuras extracelulares compuestas por cromatina remodelada y concentrada con ADN, histonas y proteínas de los neutrófilos y son un mecanismo de acción de los neutrófilos que se describió por primera vez en 2004. Se ha estudiado que pueden desempeñar un papel patogénico en la AR y podrían ser fuente de autoantígenos e incrementar la respuesta inmunológica en forma de autoanticuerpos en esta enfermedad. También se ha estudiado el posible papel de las NET y otros marcadores de activación neutrofílica como biomarcadores de actividad en la AR y otras enfermedades inmunomediadas.En el presente artículo se revisa el papel de las NET en la AR. Se revisa el papel del neutrófilo y los últimos avances en NET, especialmente en su participación en los fenómenos de autoinmunidad en la AR. Por último, se hace una revisión de la literatura sobre la determinación de NET en sangre periférica y su relación como biomarcador de actividad de la AR y su posible papel para monitorizar la enfermedad.(AU)

Interplay between tumor-derived factors and tumor-associated neutrophils: opportunities for therapeutic interventions in cancer

Neutrophils have emerged as important players in the tumor microenvironment, largely attributed to their plasticity and heterogeneity. Evidence accumulated thus far indicates that neutrophils signaled by external cues can promote tumor progression via several mechanisms. Hence, in our quest to target tumor-associated neutrophils to improve treatment, understanding the mechanisms by which tumor-derived factors regulate neutrophils to gain pro-tumor functions and the feedback loop by which these neutrophils promote tumor progression is very crucial. Herein, we review the published data on how tumor-derived factors alter neutrophils phenotype to promote tumor progression with particular emphasis on immunosuppression, autophagy, angiogenesis, tumor proliferation, metastasis, and therapeutic resistance. These deeper insights could provide a wider view and novel therapeutic approach to neutrophil-targeted therapy in cancer (AU)

Utility of neutrophil/albumin ratio and C-reactive protein/albumin ratio as novel inflammatory markers in Behcet's disease / Utilidad de la relación neutrófilos/albúmina y la relación proteína C reactiva/albúmina como nuevos marcadores inflamatorios en la enfermedad de Behçet

Introduction and objectives: Behcet's disease (BD) is an autoimmune systemic inflammatory disease, and its exact pathogenesis is unknown. There are currently no specific tests to evaluate the disease activity of BD, making its management more difficult. This study aims to determine the neutrophil/albumin ratio (NAR) and C-reactive protein (CRP) to albumin ratio (CAR) and investigate their associations with clinical findings in patients with BD and to determine optimum cutoff levels of CAR and NAR. Methods: The study included 75 consecutively recruited patients with BD with a mean age of 33.29±6.23 years and disease duration of 7.21±4.64 years, as well as 75 healthy participants. Clinical characteristics and laboratory data were obtained. Disease activity was assessed using the BD current activity form score (BDCAF). Results: NAR and CAR were elevated in patients with BD compared with those of healthy controls (NAR: 1.08±0.34 vs. 0.607±0.06, CAR: 2.49±1.73 vs. 0.39±0.142; p<0.0001), as well as in active BD versus inactive BD. Both NAR and CAR were significantly correlated with CRP, active uveitis, and BDCAF score (p≤0.05). In patients with active BD, the cutoff value of NAR was >0.9744 (sensitivity: 89.74%, specificity: 80.56%), while that of CAR was >2.04 (sensitivity: 74.36%, specificity: 83.33%). Conclusions: NAR and CAR are both elevated in patients with BD and may contribute to its active state. NAR and CAR can be feasible and inexpensive markers for predicting BD activity.(AU)

Introducción y objetivos: La enfermedad de Behçet (EB) es una enfermedad inflamatoria sistémica autoinmune y se desconoce su patogenia exacta. Actualmente no existen pruebas específicas para evaluar la actividad de la EB, lo que dificulta su manejo. El objetivo de este estudio es determinar la proporción neutrófilos/albúmina (NAR) y de proteína C reactiva (CRP)/albúmina (CAR) e investigar sus asociaciones con los hallazgos clínicos en pacientes con EB y determinar los niveles de corte óptimos de CAR y NAR. Métodos: El estudio incluyó a 75 pacientes con EB reclutados consecutivamente con una edad media de 33,29±6,23 años y una duración de la enfermedad de 7,21±4,64 años, así como a 75 participantes sanos. Se obtuvieron características clínicas y datos de laboratorio. La actividad de la enfermedad se evaluó utilizando la puntuación del formulario de actividad actual de la EB (BD Current Activity Form [BDCAF]). Resultados: NAR y CAR estaban elevados en pacientes con EB en comparación con controles sanos (NAR: 1,08±0,34 vs. 0,607±0,06, CAR: 2,49±1,73 vs. 0,39±0,142; p<0,0001), así como en pacientes EB activos versus EB inactivos. Tanto la NAR como la CAR se correlacionaron significativamente con la PCR, la uveítis activa y la puntuación BDCAF (p≤0,05). En pacientes con EB activa, el valor de corte de NAR fue>0,9744 (sensibilidad: 89,74%, especificidad: 80,56%), mientras que el de CAR fue>2,04 (sensibilidad: 74,36%, especificidad: 83,33%). Conclusiones: NAR y CAR están elevados en pacientes con EB y pueden contribuir a su estado activo. NAR y CAR pueden ser marcadores factibles y económicos para predecir la actividad de EB.(AU)

Relación de los índices neutrófilo-linfocito y plaquetas-linfocito con desenlaces de severidad en isquemia aguda de miembros inferiores / Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio relation with outcomes in acute lower limb ischemia

Introducción: los índices neutrófi los/linfocitos (nLr) y plaquetas/linfocitos (pLr) son marcadores de infl amaciónsistémica y podrían correlacionarse con amputación y muerte en pacientes con isquemia aguda de miembrosinferiores. Métodos: estudio retrospectivo, analítico y multicéntrico en una cohorte de pacientes con isquemia aguda demiembros inferiores no traumática ni iatrogénica entre 2017 y 2018. Se analizaron los datos clínicos y paraclínicos,se calcularon los nLr y los pLr al ingreso y se buscó su relación con la amputación y la muerte. además, se realizóel seguimiento de dichos desenlaces hasta 24 meses después del evento. Resultados: se identifi caron 140 pacientes, 56 % de género masculino y con una edad media de 76 años. Un nLr> 5,2 es un factor de riesgo para amputación intrahospitalaria (Or: 3,16) y para una menor supervivencia libre deamputación (Hr: 3,75). Un nLr > 8,4 es factor de riesgo para mortalidad intrahospitalaria (Or: 6,38) y para unasupervivencia global menor (Hr: 2,58). por su parte, el pLr > 208 se relaciona con una menor supervivencia librede amputación (Hr: 1,93) y un pLr > 226 se correlaciona con una mortalidad intrahospitalaria mayor (Or 4,48) y esun factor de riesgo para una supervivencia global menor (Hr: 2,33). Se encontró, además, que una clasifi cación derutherford IIb o III al ingreso, edad > 60 años o antecedente de enfermedad renal crónica se asociaban con unamayor mortalidad intrahospitalaria. Conclusiones: valores elevados en nLr y pLr se relacionan con un mayor riesgo de amputación y de mortalidadintrahospitalaria y con una menor supervivencia libre de amputación y supervivencia global en pacientes conisquemia aguda de extremidades inferiores, por lo que pueden usarse como una herramienta más a la hora deestadificar a los pacientes de alto riesgo que ingresan con dicho diagnóstico.(AU)

Introduction: neutrophil/lymphocyte (nLr) and platelet/lymphocyte (pLr) ratio are markers of systemic inflammation and may correlate with major outcomes in patients with acute lower limb ischemia. Methods: a retrospective, analytic and multicenter study in a cohort of patients with acute lower limb ischemia,not traumatic or iatrogenic, between 2017 and 2018. Clinical and paraclinical data were analyzed, the nLr and pLrwere calculated on admission and their relationship with amputation and death was sought. In addition, theseoutcomes were monitored up to 24 months after the event. Results: 140 patients were identified, 56 % was male and they had a mean age of 76 years old. an nLr > 5,2is a risk factor for intra-hospital amputation (Or: 3,16) and for survival free of minor amputation (Hr: 3,75). annLr > 8,4 is a risk factor for in-hospital mortality (Or: 6,38) and for a lower overall survival (Hr: 2,58). Further-more, pLr > 208 is associated with a minor amputation-free survival (Hr: 1,93) and a pLr > 226 is correlatedwith greater hospital mortality (Or 4,48) and is a risk factor for a lower overall survival (Hr: 2,33). It was alsofound that a classification of rutherford IIb or III at admission, ages > 60 years and/or history of chronic kidneydisease were associated with higher intra-hospital mortality. Conclusions: high values in the nLr and pLr are associated with increased risk of amputation and hospital mor-tality and are risk factors for free survival of amputation and reduced overall survival in patients with acute lowerlimb ischemia. therefore, it can be used as one more tool when we’re staging high-risk patients who are admittedwith such a diagnosis.(AU)

Utilidad del índice neutrófilo-linfocito en la detección de apendicectomías negativas / The role of the neutrophil-to-lymphocyte ratio in avoiding negative appendectomies

Introducción: El índice neutrófilo-linfocito (INL) es un biomarcador inflamatorio fácilmente calculable a partir del recuento diferencial de leucocitos. El objetivo de este estudio es analizar el papel del INL en la detección de apendicetomías negativas, y comparar su utilidad con otros factores clínicos, ecográficos y de laboratorio previamente descritos. Métodos: Estudio retrospectivo en pacientes menores de 16 años con sospecha de apendicitis aguda intervenidos en nuestra institución entre 2017-2020, que fueron divididos en 2 grupos según hallazgos histológicos apendiculares: Grupo AN: apendicitis negativa; ausencia de inflamación y grupo AP: apendicitis positiva; presencia de inflamación en la pared apendicular. Se analizaron las características demográficas, clínicas, ecográficas y de laboratorio. Resultados: Se incluyeron 1.269 pacientes (1.244 en el grupo AP; 25 en el grupo AN), sin diferencias demográficas entre ellos. Los pacientes del grupo AN presentaron un porcentaje significativamente menor de náuseas y vómitos en comparación con el grupo AP (p<0,001) y menor diámetro ecográfico apendicular (8,1±2,1 vs. 9,7±2,8mm; p<0,001). Los recuentos de leucocitos, neutrófilos e INL fueron significativamente superiores en el grupo AP (p<0,001), así como la proteína C reactiva (18,6 vs. 2,6; p=0,005). El análisis mediante curva ROC mostró que el INL fue el parámetro con mayor AUC (0,879) para el diagnóstico de apendicitis negativa, con un punto de corte de 2,65 con una sensibilidad del 84,2% y una especificidad del 83,8% máximas. Conclusiones: El INL es el parámetro preoperatorio que mejor distingue a los pacientes sin apendicitis aguda. Los valores inferiores a 2,65 deben hacernos sospechar otra causa diferente a la apendicitis. (AU)

Introduction: The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory biomarker that is easily calculated with data from the differential white blood cell count. The aim of our study was to analyse the role of the NLR in the detection of negative appendectomies and to compare its usefulness with other clinical, sonographic and laboratory factors previously described. Methods: We conducted a retrospective study in patients aged less than 16 years who underwent appendectomy in our hospital between 2017 and 2020. We divided patients into 2 groups based on appendiceal histological findings: NA group (negative appendicitis: absence of appendiceal inflammation) and PA group (positive appendicitis: presence of inflammation in any layer of the appendiceal wall). We analysed demographic, clinical, sonographic and laboratory characteristics. Results: We included a total of 1269 patients, 1244 in the PA group and 25 in the NA group, with no differences between groups in demographic characteristics. The proportion of patients that presented with nausea and vomiting was significantly smaller in the NA group compared to the PA group (P<.001), and there were no other differences in symptoms. The appendiceal diameter on ultrasound was significantly smaller in the NA group (8.1±2.1 vs. 9.7±2.8mm; P<.001). The white blood cell and neutrophil counts and the NLR were significantly higher in the PA group (P<.001), as was the level of C-reactive protein (18.6 vs. 2.6; P=.005). The ROC curve analysis revealed that the NLR was the parameter with the highest AUC (0.879) for the diagnosis of negative appendicitis, with a cut-off point of 2.65 for a maximum sensitivity of 84.2% and specificity of 83.8%. Conclusion: The NLR is the preoperative parameter that best discriminates patients without acute appendicitis. Values of less than 2.65 should make clinicians contemplate diagnoses other than appendicitis. (AU)

Pre-radiotherapy systemic immune inflammation index associated with overall survival in patients with advanced EGFR mutant non-small cell lung cancer receiving thoracic radiotherapy

Purpose This study aimed to investigate the prognostic potential of the pre-radiotherapy systemic immune-inflammation index (SII) for the survival of advanced lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations, which might provide a basis for optimizing the comprehensive treatment scheme. Methods A total of 111 lung adenocarcinoma patients with EGFR mutations, who received thoracic radiotherapy, were included in this retrospective study. The primary endpoint of the study was based on the overall survival (OS) of patients. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value of each immune inflammation index. Kaplan–Meier analysis was performed for the comparison of OS. The Cox proportional-hazard model was used for the multivariate and univariate regression analyses to determine the correlations of prognostic factors with the disease. Results SII was divided into the high SII group (≥ 620.2; 45.95%) and the low SII group (SII < 620.2; 54.05%) based on the optimal cutoff values. The median OS rates were 53.3 and 33.3 months in the low and high SII groups, respectively, showing statistically significant differences ( hazard ratio (HR) = 0.459; 95% CI 0.286–0.736; P < 0.001). The multivariate analysis showed that, after adjusting for the significant covariates, the SII values were independently associated with the improved OS of the patients (adjusted HR = 0.444; 95% CI 0.279–0.709; P = 0.001). The low NLR values were associated with the better OS of patients (HR = 0.509; 95% CI 0.326–0.792; P = 0.005) and vice versa (HR = 0.422; 95% CI 0.213–0.836; P < 0.001). The patients in the low LMR group before radiotherapy exhibited longer OS as compared to those in the high LMR group (HR = 0.497; 95% CI 0.308–0.802; P = 0.001) (AU)

Rosavin inhibits neutrophil extracellular traps formation to ameliorate sepsis-induced lung injury by regulating the MAPK pathway

Background: Sepsis is a systemic organ dysfunction caused by infection, and the most affected organ is the lungs. Rosavin, a traditional Tibetan medicine, exerts an impressive anti--inflammatory effect. However, its effects on sepsis-related lung damage have not been investigated. Purpose: This study aimed to investigate the effects of Rosavin on cecal ligation and puncture (CLP)-induced lung injury. Methods: The sepsis mouse model was established by CLP, and the mice were pretreated with Rosavin to explore whether it contributed to the alleviation of lung injury. Hematoxylin-eosin (H&E) stain and lung injury score were used to assess the severity of lung injury. The bronchoalveolar lavage fluid (BALF) inflammatory mediators (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], IL-1β, and IL-17A) were detected by ELISA. The number of neutrophils in BALF was detected using flow cytometry. The immunofluorescence assay was used to detect histone and myeloperoxidase (MPO) in lung tissues. Then, the western blot was performed to detect the expression of mitogen-activated protein kinase (MAPK) pathways (extracellular regulated kinase [ERK], p-ERK, p38, p-p38, Jun N-terminal kinase 1/2 [JNK1/2], and p-JNK1/2) in lung tissues. Results: We found that Rosavin significantly attenuated sepsis-induced lung injury. Specifically, Rosavin significantly inhibited inflammation response by decreasing the secretion of inflammatory mediators. The level of neutrophil extracellular traps (NETs) and MPO activity in CLP were decreased after administration with Rosavin. Moreover, the western blot showed that Rosavin could suppress NETs formation by inhibiting the MAPK/ERK/p38/JNK signaling pathway. Conclusion: These findings demonstrated that Rosavin inhibited NETs formation to attenuate sepsis-induced lung injury, and the inhibitory effect may be exerted via deregulation of the MAPK pathways (AU)

The Value of Lymphocyte-CRP Ratio Predicting the Prognosis in COVID-19 Patients / El valor de la relación linfocito-PCR para predecir el pronóstico en pacientes con COVID-19

Introduction: Although prevention of the disease and its spread is the primary goal in the fight against the pandemic, studies on the correct management of those who have the disease and the predictability of the prognosis are also important. This study aimed to determine whether lymphocyte-C-reactive protein ratio, together with other inflammation markers, would be useful in predicting intensive care unit admission and mortality in Coronavirus disease 2019 cases.Material and methods: 883 patients were followed in 758 wards and 125 intensive care units. Data of the patients included in the study were compared with those admitted to the service and intensive care unit, and with those who survived and developed mortality.Results: According to the receiver operating characteristic analysis to distinguish the patients followed in the intensive care unit from the patients hospitalized in the ward that was determined that lymphocyte-C-reactive protein ratio, C-reactive protein ratio, CRP-albumin ratio, and neutrophil-lymphocyte ratio were moderate (70%–80%). D-dimer was good (80%–90%) predicting follow-up in intensive care unit. Increase in age, increase in lactate dehydrogenase and interleukin-6 levels, and uptake in tomography were determined as independent risk factors that increase intensive care unit admission. 243 (27.5%) of the patients were mortal. The mean age of the patients with a mortal course was 70±14 years, and mortality increased with increasing age. In the receiver operating characteristic analysis of patients with a mortal course that was determined that lymphocyte-C-reactive protein ratio, neutrophil-lymphocyte ratio, and D-dimer had a good (80–90%) ability to distinguish patients with a mortal course. Age, fever, and increases in lactate dehydrogenase and interleukin-6 levels were determined to be independent risk factors increasing mortality. Conclusions: ... (AU)

Introducción: Si bien la prevención de la enfermedad y su propagación es el objetivo principal en la lucha contra la pandemia, también son importantes los estudios sobre el correcto manejo de los pacientes con la enfermedad y la previsibilidad del pronóstico. El objetivo de este estudio fue determinar si la proporción de linfocitos y proteína C reactiva, junto con otros marcadores inflamatorios, sería útil para predecir el ingreso a la unidad de cuidados intensivos y la mortalidad en casos de enfermedad por coronavirus en 2019.Material y métodos: Se siguieron 883 pacientes en 758 salas y 125 unidades de cuidados intensivos. Los datos de los pacientes incluidos en el estudio se compararon con los ingresados en el servicio y unidad de cuidados intensivos, y con los que sobrevivieron y desarrollaron mortalidad.Resultados: Según el análisis de las características operativas del receptor para distinguir los pacientes seguidos en la unidad de cuidados intensivos de los pacientes hospitalizados en el servicio, se encontró que la relación linfocitos a proteína C reactiva, proteína C reactiva a albúmina y neutrófilos a la proporción de linfocitos fue moderada y el dímero D fue bueno para predecir el seguimiento en la unidad de cuidados intensivos. Se encontró que el aumento de la edad, el aumento de los niveles de lactato deshidrogenasa e interleucina-6 y la captación en la tomografía eran factores de riesgo independientes para el ingreso a la unidad de cuidados intensivos. 243 (27,5%) de los pacientes fallecieron. En el análisis de las características operativas del receptor de pacientes con un desenlace fatal, se encontró que la proporción de linfocitos a proteína C reactiva, la proporción de neutrófilos a linfocitos y el dímero D tenían una buena capacidad para discriminar a los pacientes con un desenlace fatal. ... (AU)

Correlación de los días de estancia hospitalaria con el índice neutrófilo-linfocítico en pacientes con diagnóstico de angina de Ludwig / Correlation of the days of hospital stay with the neutrophillymphocyte ratio in patients with a diagnosis of Ludwig's angina: pilot study

Introducción: El objetivo del presente estudio es correlacionar los días de estancia hospitalaria con el índice neutrófilo-linfocitico (INL) como biomarcador, en los pacientes con diagnóstico de angina de Ludwig que fueron admitidos en urgencias. Pacientes y métodos: Se realizó una búsqueda en los expedientes clínicos del hospital, donde solo se obtuvieron los que tenían diagnóstico de angina de Ludwig desde junio de 2016 hasta junio de 2020, y que cumplieran con los criterios de selección. Posteriormente se recabaron los datos sociodemográficos, días de hospitalización, biometría hemática y valores de neutrófilos y linfocitos para su posterior análisis estadístico. Resultados: Obtuvimos 21 pacientes (9 mujeres y 12 hombres). La edad promedio fue de 43,1 años (rango: 27-70 años). Se transformó la variable de días de hospitalización: en corta estancia hospitalaria aquellos pacientes que estuvieron hospitalizados 5 días o menos; y los de larga estancia hospitalaria aquellos pacientes que estuvieron hospitalizados 6 días o más, para el INL se consideró un índice alto aquellos pacientes que se encontraran con un INL ≥ 6 y un índice bajo aquellos pacientes con un índice ≤ 5, tomando en cuenta el punto de corte con respecto a estudios previamente realizados. Se observó que aquellos pacientes con un INL alto tuvieron una estancia hospitalaria larga, y de acuerdo con los resultados obtuvimos significación estadística (p = 0,02). Conclusiones: El INL parece ser un buen biomarcador para predecir los días de estancia hospitalaria de los pacientes con angina de Ludwig. Sin embargo, se necesitan más estudios para confirmar nuestros resultados. (AU)

Introduction: The aim of this study is to correlate the number of days of hospital stay with the neutrophil-lymphocyte index (NLI) as a biomarker in patients diagnosed with Ludwig's angina who were admitted to the emergency department. Patients and methods: A search was conducted in the hospital's medical records, where only those with a diagnosis of Ludwig's angina from June 2016 to June 2020 and that met the selection criteria were obtained. Afterwards, sociodemographic data, days of hospitalization, hematological parameters, and values of neutrophils and lymphocytes were collected for subsequent statistical analysis. Results: We obtained 21 patients (9 females and 12 males). The average age was 43.1 years (range: 27-70 years). The variable of days of hospitalization was transformed into: short hospital stay for patients who were hospitalized for 5 days or less, and long hospital stay for patients who were hospitalized for 6 days or more. For the NLI, a high index was considered for patients with an NLI ≥ 6 and a low index for patients with an NLI ≤ 5, taking into account the cut-off point with respect to previously conducted studies. We observed that patients with a high NLI had a long hospital stay and according to the results, we obtained statistical significance (p = 0.02). Conclusions: The NLI appears to be a good biomarker for predicting the number of days of hospital stay for patients with Ludwig's angina. However, more studies are needed to confirm our results. (AU)

Neutrophil-to-lymphocyte ratio is not associated with risk of sarcopenia in elderly COVID-19 patients / La proporción de neutrófilos a linfocitos no está asociada con el riesgo de sarcopenia en pacientes ancianos con COVID-19

Background: To assess the existence of association between neutrophil to lymphocyte ratio (NLR) and the risk of sarcopenia in COVID-19 patients. Methods: A retrospective cross-sectional study was conducted in a university hospital with patients with an active COVID-19 infection admitted to the nursing ward or intensive care unit (ICU) between September to December 2020. Sarcopenia risk was assessed using the Strength, Assistance for walking, Rise from a chair, Climb stairs and Falls (SARC-F). Biochemical analyses were assessed by circulating of C-reactive protein, D-dimer, neutrophils, lymphocytes count and NLR. Sixty-eight patients were evaluated and divided into tertiles of NLR values and the association between NLR and sarcopenia risk were tested using the linear regression analyses and p<0.05 were considered as significant. Results: Sixty-eight patients were evaluated and divided in NLR tertiles being the 1st (men=52.2%; 71.1±9.0 y; NLR: 1.1–3.85), 2nd (women=78.3%; 73.2±9.1 y; NLR: 3.9–6.0) and 3rd (men=72.7%; 71.7±10.4 y; NLR: 6.5–20.0). There was a difference between the tertiles in relation to the first to the biochemical parameters of total neutrophils count (p=0.001), C-reactive protein (p=0.012), and D-dimer (p=0.012). However, no difference was found in linear regression analysis between tertiles of NLR and SARC-F, if in total sample (p=0.054) or divided by sex, if men (p=0.369) or women (p=0.064). Conclusion: In elderly patients hospitalized with COVID-19, we do not find an association between the risk of sarcopenia and NLR. (AU)

Objetivo: Evaluar la existencia de asociación entre la relación neutrófilos a linfocitos (RNL) y el riesgo de sarcopenia en pacientes con COVID-19. Métodos: Se realizó un estudio transversal retrospectivo en un hospital universitario con pacientes con infección activa por COVID-19 ingresados en sala de enfermería o unidad de cuidados intensivos (UCI) entre septiembre a diciembre de 2020. El riesgo de sarcopenia se evaluó utilizando: fuerza, ayuda para caminar, levantarse de una silla, subir escaleras y caídas (SARC-F). Los análisis bioquímicos se evaluaron mediante circulación de proteína C reactiva, dímero D, neutrófilos, recuento de linfocitos y RNL. Sesenta y ocho pacientes fueron evaluados y divididos en terciles de valores de RNL y la asociación entre RNL y el riesgo de sarcopenia se evaluó mediante análisis de regresión lineal; p<0,05 se consideró significativo. Resultados: Sesenta y ocho pacientes fueron evaluados y divididos en terciles de RNL, siendo el primero (hombres=52,2%; 71,1±9,0años; RNL: 1,1-3,85), el segundo (mujeres=78,3%; 73,2±9,1años; RNL: 3,9-6,0) y el tercero (hombres=72,7%; 71,7±10,4años; RNL: 6,5-20,0). Hubo diferencia entre los terciles con relación al primero en los parámetros bioquímicos de recuento de neutrófilos totales (p=0,001), proteínaC reactiva (p=0,012) y dímeroD (p=0,012). Sin embargo, no se encontró diferencia en el análisis de regresión lineal entre terciles de RNL y SARC-F, si en muestra total (p=0,054) o dividida por sexo, si hombres (p=0,369) o mujeres (p=0,064). Conclusiones: En pacientes ancianos hospitalizados con COVID-19 no encontramos asociación entre el riesgo de sarcopenia y RNL. (AU)

Prognostic Value of the Neutrophil/Lymphocyte Ratio in Squamous Cell Carcinoma of the Penis

Introduction: To determine the predictive role of the neutrophil/lymphocyte ratio (NLR) in the prognosis and survival of patients with squamous cell carcinoma of the penis. Materials and Methods: A retrospective cohort study of 96 patients with squamous cell carcinoma of the penis (SCCP). Clinical and histological data, bloodwork and disease evolution information were collected. We determined neutrophil/lymphocyte ratios and analyzed their relationship to prognosis and survival. Results: The mean age of patients was 72,1 years. The average follow-up time for the sample was 3,8 years (CI 95%: 3,0–4,6). Compared to patients with NLR <3, those with NLR >3 presented a higher proportion of cancers in stages cN1 (29.7% vs 6.8%; p = 0,004), stages pT3 and pT4 (24,3% vs 9,5%; p = 0,05), and stages TNM III and IV (32,4% vs 10,2%; p = 0,01); additionally, there were more cases of perineural invasion in the NLR >3 patients (29,7% vs 10,2%; p = 0,03). The mean overall survival (OS) was 7,9 years (CI 95%: 6,2–9,6) and the cancer-specific survival (CSS), 1,3 years (CI 95%: 0,7–1,9). There were no differences in OS, CSS or in progression-free survival (PFS) in patients with NLR >3 compared to those with NLR <3 . However, in the Cox regression analysis, a higher NLR was independently associated (along with metastasis and need for adjuvant treatment) with lower PFS, with an HR: 1,27 (CI 95%: 1,02–1,57; p = 0,02). Conclusions: The utilization of NLR in clinical practice can be considered an additional tool to aid in the diagnosis and prognosis of patients with squamous cell carcinoma of the penis (AU)

Mycobacterium abscessus Infected Neutrophils as an In Vitro Model for Bronchiectasis. Neutrophils Prevent Mycobacterial Aggregation

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The Clinicopathological and Prognostic Value of NLR, PLR and MLR in Non-Muscular Invasive Bladder Cancer

Background: The clinicopathological and prognostic relevance of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) in non-muscular invasive bladder cancer (NMIBC) was investigated. Methods: All patients who underwent transurethral resection of bladder tumor (TURBT) and postoperative intravesical chemotherapy had their peripheral blood levels of NLR, PLR, and MLR quantified. The preoperative peripheral blood levels of NLR, PLR, and MLR were analyzed in patients with G1, G2, and G3 NMIBC. A total of 208 patients was divided into poor prognosis (PP, with recurrence, n=51) and good prognosis (GP, no recurrence, n=157) groups, according to whether the recurrence of NMIBC was observed at 1-year follow-up after treatment. Univariate and multivariate logistic regression analyses were performed to evaluate the prognostic factors in NMIBC. In addition, receiver operating characteristic (ROC) curves were used to analyze the prognostic performance of NLR, PLR, and MLR in NMIBC. Results: The preoperative peripheral blood level of PLR was significantly increased in patients with G3 NMIBC compared with that in patients with G1 (p < 0.05) and G2 NMIBC (p < 0.05). The results of univariate and multivariate logistic regression analyses showed that the tumor diameter, differentiation grade, and preoperative peripheral blood levels of NLR, PLR, and MLR were independent prognostic factors for NMIBC recurrence (p < 0.05). Compared with the NMIBC patients without recurrence, 3.490%, 177.575% and 3.175% were determined as the optimum prognostic cutoffs for NLR, PLR, and MLR, respectively. ROC curve was used to evaluate the sensitivity, specificity, and area under the curve (AUC) of NLR, PLR, MLR, and combinations. In contrast to NLR, PLR, or MLR, the combination of NLR, PLR, and MLR (AUC 0.758, sensitivity 66.70%, specificity 89.80%,Youden index 0.565) (AU)

Treating Neutrophilic Inflammation in Airways Diseases

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