Testes de Triagem Prevendo Metástase de Câncer na Etiologia do Derrame Pericárdico: HALP Score e PNI / Screening Tests Predicting Cancer Metastasis in the Etiology of Pericardial Effusion: HALP Score and PNI

Resumo Fundamento: A triagem do câncer é absolutamente necessária em pacientes com derrame pericárdico, pois o câncer é uma das doenças mais graves em sua etiologia. Estudos anteriores indicaram que o índice de inflamação imunológica sistêmica (IIS), o índice prognóstico nutricional (PNI) e o escore de hemoglobina, albumina, linfócitos e plaquetas (HALP) podem ser escores relacionados ao câncer. Objetivos: Este estudo foi iniciado considerando que esses sistemas de pontuação poderiam prever o câncer na etiologia de pacientes com derrame pericárdico. Métodos: Os pacientes submetidos à pericardiocentese entre 2006 e 2022 foram analisados retrospectivamente. A pericardiocentese foi realizada em um total de 283 pacientes com derrame pericárdico ou tamponamento cardíaco de moderado a grande no período especificado. Os índices de HALP, PNI e IIS foram calculados do sangue venoso periférico retirado antes do procedimento de pericardiocentese. O nível de significância estatística foi aceito em p<0,05. Resultados: O escore HALP foi de 0,173 (0,125-0,175) em pacientes com câncer. Detectou-se que em pacientes não oncológicos o escore foi de 0,32 (0,20-0,49; p<0,001). O escore de PNI foi de 33,1±5,6 em pacientes com câncer. Detectou-se que em pacientes não oncológicos o escore foi 39,8±4,8 (p<0,001). Conclusão: Os escores HALP e PNI são testes de triagem de câncer fáceis e rápidos que podem prever metástases de câncer na etiologia de pacientes com derrame pericárdico.

Abstract Background: Cancer screening is absolutely necessary in patients with pericardial effusion, given that cancer is one of the most serious diseases in the etiology of pericardial effusion. In previous studies, it was stated that the systemic immune-inflammation index (SII); the prognostic nutrition index (PNI); and the hemoglobin, albumin, lymphocyte, platelet (HALP) score can produce scores related to cancer. Objectives: This study began considering that these scoring systems could predict cancer in the etiology of patients with pericardial effusion. Methods: This study produced a retrospective analysis of patients who underwent pericardiocentesis between 2006 and 2022. Pericardiocentesis was performed in a total of 283 patients with moderate-to-large pericardial effusion or pericardial tamponade within the specified period. HALP, PNI, and SII scores were calculated according to the peripheral venous blood taken before the pericardiocentesis procedure. The statistical significance level was set at p<0.05. Results: The HALP score proved to be 0.173 (0.125-0.175) in cancer patients and 0.32 (0.20-0.49) in non-cancer patients (p<0.001). The PNI score proved to be 33.1±5.6 in cancer patients and 39.8±4.8 in non-cancer patients (p<0.001). Conclusion: The HALP score and PNI proved to be easy and fast cancer screening tests that can predict cancer metastasis in the etiology of patients with pericardial effusion.

Lung transplantation after paraquat poisoning in an adolescent: one case report and literature review / 器官移植

Objective To summarize the effect of the timing of lung transplantation and related treatment measures on clinical prognosis of patients with paraquat poisoning. Methods Clinical data of a patient with paraquat poisoning undergoing bilateral lung transplantation were retrospectively analyzed. Clinical manifestations, auxiliary examination, diagnosis and treatment of this patient were summarized and analyzed. Results A 17-year-old adolescent was admitted to hospital due to nausea, vomiting, cough and systemic fatigue after oral intake of 20-30 mL of 25% paraquat. After symptomatic support treatment, the oxygen saturation was not improved, and pulmonary fibrosis continued to progress. Therefore, sequential bilateral lung transplantation was performed under extracorporeal membrane oxygenation (ECMO). After postoperative rehabilitation and active prevention and treatment for postoperative complications, the patient was discharged at postoperative 50 d. Conclusions The timing of lung transplantation after paraquat poisoning may be selected when the liver and kidney function start to recover. Active and targeted prevention of potential pathogen infection in perioperative period and early rehabilitation training contribute to improving clinical prognosis of lung transplant recipients.

The value of NLR in predicting the efficacy of preoperative nimotuzumab combined with neoadjuvant chemotherapy for local advanced oral squamous cell carcinoma / 口腔疾病防治

Objective@#To investigate the value of the peripheral blood neutrophil to lymphocyte ratio (NLR) before nimotuzumab combined with neoadjuvant chemotherapy in predicting the short-term efficacy of neoadjuvant therapy for advanced oral squamous cell carcinoma (OSCC).@*Methods@#With the approval of the Ethics Committee and the informed consent of the patients, 59 patients with stage Ⅲ and Ⅳ OSCC who were admitted to the Oral and Maxillofacial Surgery Department of the First Hospital of Shanxi Medical University from September 2020 to June 2023 were enrolled. All the patients had complete clinical data, were pathologically diagnosed with squamous cell carcinoma, and received preoperative and received preoperative nimotuzumab + TP (docetaxel + cisplatin) neoadjuvant chemotherapy. The clinical data were analyzed, and the neutrophil and lymphocyte counts in peripheral blood were collected before and after nimotuzumab combined with neoadjuvant chemotherapy. The NLR was calculated, and the threshold value was calculated using the receiver operating characteristic (ROC) curve. Patients were divided into a high NLR group and a low NLR group according to the NLR threshold before nimotuzumab combined with neoadjuvant chemotherapy with TP. The clinical efficacy after nimotuzumab combined with neoadjuvant chemotherapy with TP was evaluated according to the evaluation criteria for solid tumor efficacy, and the correlation between the NLR and recent neoadjuvant therapy efficacy was analyzed. Immunohistochemical staining was used to detect the expression of epidermal growth factor receptor (EGFR) in OSCC tissues before and after nimotuzumab combined with neoadjuvant chemotherapy with TP and to analyze whether the expression of EGFR differed among the different NLR groups.@*Results@#A total of 59 patients with advanced OSCC were included. According to the ROC curve, the NLR threshold was 2.377, and the patients were divided into a <2.377 group (low NLR group), with 24 patients, and a>2.377 group (high NLR group), with 35 patients. The short-term neoadjuvant therapy effect was significantly greater in the lower NLR group than in the higher NLR group (P<0.05); EGFR expression in both the low NLR group and the high NLR group decreased after nimotuzumab combined with neoadjuvant chemotherapy with TP, and the decrease in the low NLR group was significantly greater than that in the high NLR group (P<0.05).@*Conclusion@#A low NLR before nimotuzumab combined with neoadjuvant chemotherapy with TP is associated with better neoadjuvant therapy outcomes, and such patients are more likely to benefit from preoperative nimotuzumab combined with neoadjuvant chemotherapy.

Effect of LAG3 deficiency on natural killer cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis / 中国血吸虫病防治杂志

Objective To investigate the effect of LAG-3 deficiency (LAG3-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. Methods C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. Results Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3-/- group than in the WT group (t = −3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3-/- and WT groups in terms of the percentages of IFN-γ (t = −0.723, P > 0.05), TNF-α (t = −0.659, P > 0.05), IL-4 (t = −0.263, P > 0.05), IL-10 (t = −0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = −4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = −1.902, P > 0.05), IL-4 (t = −1.333, P > 0.05), IL-10 (t = −1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). Conclusions During the course of E. multilocularis infections, LAG3-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.

Effects of occupational radiation exposure on peripheral blood lymphocyte count and cell cycle in logging workers / 中国辐射卫生

Objective To investigate the effects of prolonged low-dose neutron-γ radiation on peripheral blood lymphocytes of logging workers. Methods The health information of workers in a logging company was collected by on-site blood sample collection and questionnaire survey. Individual doses of γ and neutron radiation were recorded using LiF elements and CR-39, respectively. Lymphocyte count in peripheral blood was measured by blood cytometer. Cell cycle and cyclins were detected by flow cytometry. Results The annual dose of some logging workers exceeded 5 mSv. Lymphocyte counts showed a difference of 15% between the group exposed to the lowest annual dose of 0–1 mSv (mean: 2.45 × 109/L) and the group exposed to the highest annual dose of 5–25 mSv (mean: 2.08 × 109/L). In comparison to pre-shift workers, logging workers exhibited a G1-phase arrest in the lymphocyte cycle, along with increased expression of cyclins p21 and CDK2. Conclusion Prolonged exposure to low-dose neutron-γ radiation leads to reduced lymphocyte counts as well as changes in lymphocyte cycle and cyclin expression.

Subpoblaciones de linfocitos T en adultos mayores cubanos con leucemia linfoide crónica / Subpopulations of T lymphocytes in Cuban older adults with chronic lymphoid leukemia

Introducción: la inmunosenescencia está asociada con un mayor riesgo de desarrollo de cáncer. Dentro de las hemopatías malignas que afectan a este grupo de edad, está la leucemia linfoide crónica (LLC), caracterizada por trastornos en la inmunidad adaptativa que incluye las subpoblaciones de linfocitos T. Objetivo: Determinar la frecuencia de las subpoblaciones de linfocitos T en los pacientes adultos mayores con leucemia linfoide crónica evaluados en el Instituto de Hematología e Inmunología de Cuba. Métodos: Se realizó un estudio transversal en 30 adultos mayores con leucemia linfoide crónica. Se cuantificaron los linfocitos TCD3+CD4+ y TCD3+CD8+ en sangre periférica por citometría de flujo. Para la lectura y el análisis de los datos se empleó un citómetro de flujo Beckman Coulter Gallios. Se utilizaron los valores porcentuales, la media y la desviación estándar. Se consideró estadísticamente significativo si p≤0.05. Resultados: Hubo un predominio de hombres que representaron el 56,7 por ciento y del grupo de 70-79 años de edad. No se reportó ningún adulto mayor con LLC con valores altos ni normales de linfocitos TCD3+CD4+. Predominaron los hombres con valores bajos porcentuales de linfocitos TCD3+CD4+, TCD3+CD8+ e inversión del índice CD4/CD8 en relación con las mujeres. Conclusiones: Los adultos mayores con LLC presentan alteraciones en el número de las subpoblaciones de linfocitos T. La acción de estas células en relación al crecimiento de células B malignas aún es desconocido y resulta importante determinar si esto puede reflejar un intento de evasión de las células tumorales al control inmunológico(AU)

Introduction: Immunosenescence is associated with an increased risk of cancer development. Among the malignant hemopathies that affect this age group, it is chronic lymphoid leukemia (CLL), characterized by disorders in adaptive immunity, which include subpopulations of T lymphocytes. Objective: To determine frequency of T lymphocyte subpopulations in older adult patients with chronic lymphoid leukemia evaluated at the Institute of Hematology and Immunology of Cuba. Methods: A cross-sectional study was conducted in 30 older adults with chronic lymphoid leukemia. TCD3+CD4+ and TCD3+CD8+ lymphocytes were quantified in peripheral blood by flow cytometry. A Beckman Coulter Gallios flow cytometer was used to read and analyze the data. The percentage values, the mean and the standard deviation were used. It was considered statistically significant if p≤0.05. Results: There was a predominance of men who represented 56.7 percent and the age group of 70-79 years. No older adults with CLL with high or normal values of TCD3+CD4+ lymphocytes were reported. Men predominated with low percentage values of TCD3+CD4+, TCD3+CD8+ lymphocytes and inversion of the CD4/CD8 ratio in relation to women. Conclusions: Older adult with CLL present alterations in the number of T lymphocyte subpopulations. The role of these cells in relation to the growth of malignant B cells it is unknown and it turns out important to determine if this may reflect an attempt to evade tumor cells from immune control(AU)

Neutrophil-lymphocyte ratio, red cell distribution width and mean platelet volume as practical markers in febrile seizure classification / Proporção entre linfócitos e neutrófilos, amplitude de distribuição de hemácias e volume médio de plaquetas como marcadores práticos na classificação de convulsões febris

ABSTRACT Objective: To examine the neutrophil-lymphocyte ratio, red cell distribution width and mean platelet volume in patients with febrile seizure and to determine their role in febrile seizure classification. Methods: This was a retrospective hospital-based study conducted among patients aged 5 to 72 months admitted with febrile seizure. Children who had febrile seizures due to upper respiratory tract infection were included in the study. The children were divided into two groups: simple febrile seizures and complex febrile seizures. Patients with a history of febrile status epilepticus, previous convulsions, use of antiepileptic or other chronic drugs, foci of infection other than the upper respiratory tract infection, abnormal biochemical parameters, and chronic mental or physical disease were excluded from the study. Clinical and laboratory findings of the patients were obtained from digital medical records. Results: The records of 112 febrile seizure patients were reviewed, and 89 were grouped as simple and 23 as complex febrile seizures. Although there was no statistically significant difference between the two groups in terms of the mean red cell distribution width values (p=0.703), neutrophil-lymphocyte ratio and mean platelet volume were significantly higher in patients with complex febrile seizures (p=0.034, p=0.037; respectively). Conclusions: This study showed that neutrophil-lymphocyte ratio and mean platelet volume could be practical and inexpensive clinical markers for febrile seizure classification. A similar result could not be reached for red cell distribution width in this study. These findings should be supported by multicenter studies with large samples.

RESUMO Objetivo: Examinar a relação linfócitos-neutrófilos, amplitude de distribuição de hemácias e volume médio de plaquetas em pacientes com convulsão febril, e determinar seu papel na classificação de convulsão febril. Métodos: Este foi um estudo retrospectivo de base hospitalar realizado com pacientes de 5 a 72 meses admitidos com convulsão febril. Crianças que tiveram convulsões febris em razão de infecção do trato respiratório superior foram incluídas no estudo. As crianças foram divididas em dois grupos: convulsões febris simples e complexas. Pacientes com história de Status epiléptico febril, convulsões prévias, uso de drogas antiepilépticas ou outras drogas crônicas, com focos de infecção que não a do trato respiratório superior, parâmetros bioquímicos anormais e doenças crônicas mentais ou físicas foram excluídos do estudo. Os achados clínicos e laboratoriais dos pacientes foram obtidos a partir dos prontuários médicos digitais. Resultados: Registros de 112 pacientes com convulsão febril foram revisados: 89 com convulsões febris simples e 23 com complexas. Embora não tenha havido diferença estatisticamente significativa entre os dois grupos em termos de valor médio de amplitude de distribuição de hemácias (p=0,703), a relação linfócitos-neutrófilos e o volume médio de plaquetas foram significativamente mais elevados em pacientes com convulsões febris simples (p=0,034, p=0,037; respectivamente). Conclusões: Este estudo mostrou que a relação linfócitos-neutrófilos e o volume médio de plaquetas podem ser marcadores clínicos práticos e de baixo custo para a classificação de convulsão febril. Um resultado semelhante não pôde ser alcançado para a amplitude de distribuição de hemácias neste estudo. Esses achados devem ser apoiados por estudos multicêntricos com grandes amostras.

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.

Evaluación comparativa de medición de linfocitos CD4+ por dos técnicas: estándar nacional versus test rápido de ejecución local

Antecedentes: El recuento de linfocitos CD4+ (LTCD4) es una herramienta fundamental para la evaluación y seguimiento de los pacientes que viven con VIH. En Chile, la medición de LTCD4 estandarizada es por citometría de flujo. En el sistema público se realiza en forma centralizada en tres centros. Actualmente existen tecnologías de medición rápida de recuento de LTCD4 en el lugar de atención, permitiendo optimizar la atención de pacientes con infección por VIH. Objetivo: Comparar la precisión de un test rápido de ejecución local versus la técnica estándar. Metodología: Realización de ambas técnicas en un grupo de 102 pacientes durante su control regular de salud. Resultados: El rango de variación promedio de los resultados entre las dos técnicas fue de 10%, con una concordancia en los recuentos de LTCD4 de 97% para el rango de CD4 < 200 cél/uL, de 88% para los pacientes con recuento de LTCD4 entre 200 y 349 cél/uL y de 67% en los rangos superiores. Conclusión: La técnica por test rápido es un sistema fácil de aplicar, de bajo costo, con alta concordancia con la técnica estándar, lo que debería considerarse en la atención de los pacientes que viven con VIH.

Background: The CD4+ lymphocyte cell count is an instrumental tool for the assessment and follow-up in the therapeutic management of patients living with HIV. In Chile, the standardized CD4+ lymphocyte count technique is by flow cytometry. In the public health system, it is performed centralized in 3 sites. Currently, there are technologies that allow measuring the CD4 lymphocyte count at the point of care, allowing to optimize the care of HIV-infected patients. Aim: To compare the accuracy of a point of care rapid test versus the standard technique in patients under regular care at a single HIV center. Results: The average variation of the results between the two techniques was 10%, with a 97% concordance in CD4 range values for patients with CD4 below 200 cells/uL, 88% for CD4 counts between 200 and 349 cells/uL. and 67% above that range. Conclusion: This point of care test is an easy-to-operate, low-cost system with high correlation with the standard technique and should be considered in the care of patients living with HIV.

Changes of lymphocyte subsets in smear-negative pulmonary tuberculosis

Background and Aims: The host immune system plays an important role in the pathogenesis and defense mechanism of Mycobacterium tuberculosis (Mtb). This study aimed to explore the different changes in the immune system between smear-negative pulmonary tuberculosis (PTB) and smear-positive PTB patients. Materials and Methods: A total of 85 active PTB patients and 50 healthy adults were enrolled. The participants were divided into smear-negative PTB, smear-positive PTB, and control groups. Chest computed tomography (CT) and lymphocyte subgroup counts in peripheral blood were measured in all participants. Results: There were higher numbers of CD4 + T-cells, NK cells, and pulmonary cavities in the smear-positive PTB group, whereas the numbers of B-ells were significantly increased in the smear-negative PTB group. Conclusions: Smear-negative PTB showed fewer pulmonary cavities, mild inflammatory response, lower numbers of immune cells, and higher numbers of B- cells.

Nuevo sistema de calificación diagnóstica para apendicitis pediátrica basado en parámetros hematológicos ajustados por edad y sexo / A novel diagnostic scoring system for pediatric appendicitis based on age and sex-adjusted hematological parameters

Resumen Antecedentes: El diagnóstico de apendicitis aguda representa un reto en pacientes pediátricos. Objetivo: Establecer la importancia del índice neutrófilos-linfocitos (INL), índice plaquetas-linfocitos (IPL) y otros parámetros hematológicos ajustados por edad y sexo en la predicción de apendicitis aguda, así como describir un nuevo sistema de calificación. Material y métodos: Se analizaron retrospectivamente expedientes clínicos de 946 niños hospitalizados por apendicitis aguda. Se desarrolló un sistema de calificación basado en INL, IPL, ILM y proteína C reactiva (PCR) ajustados por edad y sexo. Resultados: Los pacientes se dividieron en grupo I de exploración negativa y grupo II de apendicitis aguda; las medias de edad correspondientes fueron 12.20 ± 2.31 y 11.56 ± 3.11. El recuento leucocitario, porcentaje de neutrófilos, INL, IPL, ILM y PCR fueron superiores en el grupo II. La calificación osciló entre 0 y 8 puntos; se determinó que 4.5 fue el mejor punto de corte para apendicitis aguda con mayor área bajo la curva (0.96), sensibilidad (94 %), especificidad (86 %), valor predictivo positivo (97.5 %), valor predictivo negativo (65 %), precisión (92.6 %) y tasa de clasificación errónea (7.4 %). Conclusión: El sistema de calificación que se propone, calculado por edad y sexo de los pacientes, se puede utilizar para evitar cirugías innecesarias.

Abstract Background: Acute appendicitis diagnosis can sometimes be a real challenge in pediatric patients. Objective: To establish the importance of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and other hematological parameters adjusted for age and sex in the prediction of acute appendicitis, as well as to describe a new scoring system. Material and methods: Medical records of 946 children hospitalized for acute appendicitis were retrospectively analyzed. A scoring system based on NLR, PLR, lymphocyte/monocyte ratio (LMR), and C-reactive protein (CRP) adjusted for age and sex was developed. Results: Patients were divided into group I, with negative examination, and group II, with acute appendicitis; mean ages were 12.20 ± 2.31 and 11.56 ± 3.11, respectively. Leukocyte count, neutrophil percentage, NLR, PLR, LMR and PCR were higher in group II. The scores ranged from 0 to 8 points; 4.5 was determined to be the best cut-off point for acute appendicitis with the highest area under the curve (0.96), sensitivity (94%), specificity (86%), positive predictive value (97.5%), negative predictive value (65%), accuracy (92.6%) and misclassification rate (7.4%). Conclusion: The proposed scoring system, calculated based on patient age and gender, can be used for unnecessary surgeries to be avoided.

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.

Significance of immune-inflammatory markers in predicting clinical outcome of COVID-19 patients

Background: The epidemic of coronavirus disease 2019 (COVID-19) has been rapidly spreading on a global scale affecting many countries and territories. There is rapid onset of generalized inflammation resulting in acute respiratory distress syndrome. We, thus, aimed to explore the potential of immune-inflammatory parameters in predicting the severity of COVID-19. Materials and Methods: Age, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), Lactate Dehydrogenase (LDH), C-reaction protein (CRP), and procalcitonin (PCT) of 611 patients with laboratory-confirmed COVID-19 were investigated and compared. Patients were divided on the basis of severity and survival into two groups. Data were expressed as mean or median values and percentages. The receiver operating characteristic curve was applied to determine the optimal cut-off values of these biomarkers. Results: The median age was 50 years and the male to female ratio was 3.7:1. The mean NLR, LMR, PLR, LDH, CRP, and Procalcitonin for the non-severe group were 4.16, 10.8, 133.7, 666.1, 49.9, and 0.15, respectively. In the severe group mean values of the above-mentioned immune-inflammatory markers were 17.8, 4.69, 268.2, 1277, 158.6, and 3.05, respectively. Elevated levels were significantly associated with disease severity. In ROC curve analysis, NLR had the largest area under the curve at 0.923 with the highest specificity (0.83) and sensitivity (0.88). Conclusion: This study shows that NLR, PLR, LDH, CRP, and Procalcitonin may be a rapid, widely available, useful predictive factor for determining the severity of COVID-19 patients.

Quality evaluation of anti-PD-1/CTLA-4 bispecific antibody / 中国生物制品学杂志

@#Objective Establish quality control methods for critical quality attribute of bispecific antibody against programmed cell death protein 1(PD-1)/cytotoxic T-lymphocyte-associated protein 4(CTLA-4).Methods The biological activity of PD-1 target was determined by reporter gene assay,and the competitive binding activity of CTLA-4 target was determined by flow cytometry;The antibody molecular size variants were controlled by reducing/non-reducing capillary electrophoresis-sodium dodecyl sulfonate(CE-SDS) and size exclusion chromatography-high performance liquid chromatography(SEC-HPLC);Charge heterogeneity was determined by imaging capillary isoelectric focusing electrophoresis(iCIEF);Bispecific anti-PD-1/CTLA-4 antibody was identified by peptide map analysis;Glycosylation was analysed by high performance liquid chromatography(HPLC)Results The concentration for 50% of maximal effect(EC_(50)) of PD-1target was(6.91±0.78) nmol/L,and the relative biological potency to the reference was(103.50±13.08)% with the RSD of 12.64%;The EC_(50) of CTLA-4 target activity was(0.35±0.28) nmol/L,and the relative biological potency was(99.30±9.15)% with the RSD of 8.32%.The percentage of peak area of light chain and heavy chain of reducing CE-SDS was(98.86±0.02)%.The main peak area percentage of non-reducing CE-SDS was(93.07±0.13)%,fragment percentage was(4.44±0.13)%,and polymer percentage was(2.49±0.15)%.The peak area percentage of SEC-HPLC monomer and polymer were(97.20±0.01)% and(2.68±0.01)%,respectively.The area percentage of peak A group,peak B group,peak C group and peak D group were(38.43±0.54)%,(43.26±0.32)%,(11.31±0.14)% and(7.00±0.17)%,respectively.Peptide mapping showed the specific spectrum of the bispecific anti-PD-1/CTLA-4 antibody,which could be adopted for identification test.The highest proportion of glycotype was GOF,with a content of(41.06±0.11)%,There were three types of glycan containing sialic acid,namely G2F+G1F-NANA,G2F-NANA and G2F-2NANA,with the content of(12.44±0.12)%,(12.00±0.05)% and(5.37±0.05)%,respectively.The total content of glycan containing sialic acid was(29.80±0.20)%.Conclusion The critical quality attributes of bispecific anti-PD-1/CTLA-4 antibody were studied and the corresponding quality control methods were established to ensure its safety,effectiveness and quality control,which provides a reference for the quality control methods and strategies of this type of monoclonal antibody products.

Correlation of preoperative peripheral blood neutrophil-lymphocyte ratio and blood platelet-lymphocyte ratio and immune indexes with the prognosis of cervical cancer patients / 肿瘤研究与临床

Objective:To evaluate the value of preoperative peripheral blood neutrophil-lymphocyte ratio (NLR) and blood platelet-lymphocyte ratio (PLR) and immune indexes in the evaluation of the prognosis of cervical cancer patients.Methods:The clinical data of 283 patients with cervical cancer who underwent radical surgery in Shanxi Province Cancer Hospital from May 2017 to September 2018 were retrospectively analyzed, and 100 healthy people who underwent physical examination during the same period were collected as the healthy control group. Test results of blood cells and immune cells expressions of all subjects were collected. Peripheral blood NLR and PLR of cervical cancer patients, people in the healthy control group and cervical cancer patients with different pathological characteristics were compared. Kaplan-Meier method was used to make survival analysis and Cox regression risk model was used to analyze the factors influencing the prognosis of patients with cervical cancer.Results:The preoperative peripheral blood NLR and PLR in patients with cervical cancer was higher than that of the healthy control group (NLR: 2.53±1.35 vs. 2.00±1.21, t = 5.35, P < 0.001; PLR: 163±57 vs.144±38, t = 4.71, P = 0.006). Pathological results showed that there were no statistically significant differences in NLR and PLR in peripheral blood of cervical cancer patients with different pathological types, tumor diameter, vascular invasion, and nerve invasion (all P > 0.05), while there were statistically significant differences in NLR and PLR in peripheral blood of cervical cancer patients with different clinical staging and muscle wall invasion (all P < 0.05). When the proportions of the expression levels of preoperative CD3 positive cells, CD4 positive cells, CD8 positive cells, CD19 positive cells, CD56 positive cells, and CD127 positive cells were 60%-85%, 30%-40%, < 25%, 8%-15%, 15%-25% and < 5%, respectively, the overall survival of cervical cancer patients was the best. Univariate analysis showed that pathological type, clinical staging, vascular invasion, preoperative NLR, preoperative PLR,CD3 positive cells, CD4 positive cells, CD8 positive cells, CD19 positive cells, CD56 positive cells and CD127 positive cells were influencing factors of the overall survival of cervical cancer patients (all P < 0.05). Multivariate analysis showed that clinical staging, vascular invasion, preoperative NLR, preoperative PLR, and preoperative CD4 positive cells were independent influencing factors for the overall survival of cervical cancer patients (all P < 0.05). Conclusions:Preoperative high NLR and PLR in peripheral blood have a certain impact on the clinicopathological characteristics and poor prognosis of cervical cancer patients. When the immune cells in peripheral blood are in dynamic balance, the prognosis of cervical cancer patients is the best.

Application of free/total prostate-specific antigen ratio, peripheral blood neutrophil-to-lymphocyte ratio, interleukin-6 and prostate health index density detection in early diagnosis of prostate cancer / 肿瘤研究与临床

Objective:To investigate the clinical application of free/total prostate-specific antigen (f/tPSA), peripheral blood neutrophil-to-lymphocyte ratio (NLR), interleukin-6 (IL-6) and prostate health index density (PHID) detection in the early diagnosis of prostate cancer.Methods:The clinical data of 160 patients with abnormal prostate specific antigen (PSA) who were admitted to the Second Affiliated Hospital of Xuzhou Medical University from January 2020 to January 2022 were retrospectively analyzed. According to the pathological results of prostate biopsy or electrical resection, the patients were divided into prostate cancer group (68 cases) and benign prostatic hyperplasia group (92 cases), and 50 male healthy physical examiners in the Second Affiliated Hospital of Xuzhou Medical University during the same period were selected as healthy control group. All enrolled members were tested for total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and prostate specific antigen isoform 2 (p2PSA), IL-6 and other indicators, and the f/tPSA, prostate health index (PHI), PHID and NLR were calculated. Receiver operating characteristic (ROC) curve was plotted to compare the efficacy of each index in diagnosing and differentially diagnosing prostate cancer and benign prostatic hyperplasia.Results:The serum levels of tPSA, fPSA, p2PSA, PHI and PHID in the prostate cancer group were higher than those in the benign prostatic hyperplasia group and the healthy control group (all P < 0.05), and the serum f/tPSA was lower than that in the benign prostatic hyperplasia group and the healthy control group ( P < 0.05). The area under the curve (AUC) of PHID for the diagnosis of early stage prostate cancer was the largest [0.915 (95% CI 0.864-0.966)], followed by PHI [0.884 (95% CI 0.823-0.944)]. The sensitivity of both f/tPSA and PHI in diagnosing early stage prostate cancer was 86.80%, which was higher than other indicators; the specificity of PHID in diagnosing early stage prostate cancer was 94.00%, which was higher than other indicators. The AUC of f/tPSA for the diagnosis of benign prostatic hyperplasia was the largest [0.828 (95% CI 0.739-0.917)], followed by PHID [0.826 (95% CI 0.760-0.892)]. The sensitivity of f/tPSA in diagnosing benign prostatic hyperplasia (85.90%) was higher than other indicators, and the specificity of PHI in diagnosing benign prostatic hyperplasia (94.00%) was higher than other indicators. The AUC of fPSA, PHID, f/tPSA and p2PSA in differentiating early stage prostate cancer and benign prostatic hyperplasia were 0.752 (95% CI 0.663-0.841), 0.730 (95% CI 0.647-0.812), 0.713 (95% CI 0.623-0.803), 0.710 (95% CI 0.629-0.791), respectively, and there was no significant difference in each pairwise comparison (all P > 0.05). The sensitivity of NLR in differentiating early stage prostate cancer and benign prostatic hyperplasia was 91.20%, which was higher than other indicators, and the specificity of fPSA in differentiating early stage prostate cancer and benign prostatic hyperplasia was 94.00%, which was higher than other indicators. Conclusions:The f/tPSA, PHI and PHID detection have certain clinical values in the early diagnosis of prostate cancer, and can provide references for early diagnosis, early treatment and prognosis evaluation of high-risk population of prostate cancer.

Predictive value of blood platelet-lymphocyte ratio and neutrophil-lymphocyte ratio in the therapeutic efficacy of neoadjuvant therapy for breast cancer patients / 肿瘤研究与临床

Objective:To investigate the predictive value of the changes of platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) in the therapeutic efficacy of the neoadjuvant treatment for breast cancer.Methods:The clinical data of 72 breast cancer patients who received neoadjuvant therapy in Nantong Tumor Hospital between February 2020 and January 2022 were retrospectively analyzed and the changes of PLR and NLR before and after neoadjuvant therapy were also analyzed. The receiver operating characteristic (ROC) curves were used to assess the predictive value of PLR, NLR and their changes in pathological complete remission (pCR) after neoadjuvant therapy.Results:The area under the ROC curve of PLR and NLR before the treatment, the difference in PLR before and after the treatment (ΔPLR), the difference in NLR before and after the treatment (ΔNLR) in predicting pCR was 0.520, 0.505,0.724 and 0.686,and the corresponding cut-off value was 269.231, 2.559, -2.840 and -1.457; the patients were divided into high and low groups according to the cut-off values. NLR before the treatment was not correlated with clinicopathological characteristics (all P > 0.05),while PLR before the treatment was correlated with tumor size ( P = 0.029), and ΔPLR was correlated with progesterone receptor expression ( P = 0.025), human epidermal growth factor receptor 2 (HER2) expression ( P < 0.001), molecular subtype ( P < 0.001), N stage ( P = 0.002), clinical stage ( P = 0.002) and treatment modality ( P < 0.001). ΔNLR was associated with HER2 expression ( P = 0.002), molecular subtype ( P = 0.024), tumor size ( P = 0.007), neural invasion ( P = 0.006), N stage ( P = 0.006), clinical stage ( P = 0.016) and treatment modality ( P = 0.014). ΔPLR and ΔNLR were influencing factors for patients achieving pCR after neoadjuvant therapy (all P < 0.05). Conclusions:Stage Ⅲ invasive breast cancer patients with higher ΔPLR and ΔNLR after neoadjuvant therapy have better prognosis.

Analysis of peripheral blood lymphocyte status in low-level-viremia patients with chronic hepatitis B virus infection after nucleos(t)ide analogue treatment / 中华微生物学和免疫学杂志

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

Immunophenotype and function of peripheral blood lymphocyte subsets in Chinese rhesus macaques / 中华微生物学和免疫学杂志

Objective:To provide data reference for using Chinese rhesus macaques as research model by studying the immunophenotype and function of peripheral blood lymphocytes in Chinese rhesus macaques.Methods:By optimizing antibody clones and fluorescent colors, the lymphocyte subset assay and T cell function assay panels were determined. Then the panels were used to analyze the proportion of T, B, NK and other cell subsets in peripheral blood mononuclear cells (PBMCs) in 15 healthy Chinese rhesus monkeys, and the ability of T cells to secrete cytokines after non-specific stimulation.Results:Two multi-color flow cytometry analytic panels were established. Panel 1 could simultaneously detect a variety of lymphocyte subsets, including cytotoxic T lymphocytes, follicular helper T cells, regulatory T cells, B cells and NK cells. Panel 2 could detect the functions of multiple T cell subsets and the expression of immune checkpoint moleculars. The mean percentages of T, B, NK, Tfh, Treg, CD16 + NK and CD56 + NK cells in PBMCs of the Chinese rhesus macaques were (75.32±7.73)%, (13.22±7.50)%, (0.88±0.48)%, (0.73±0.27)%, (0.75±0.43)%, (47.87±22.35)% and (10.69±12.41)%. After non-specific stimulation, the proportion of CD4 + T cells secreting IL-2 and TNF-α was higher than that of CD8 + T cells, and the proportion of CD8 + T cells secreting CD107a and IFN-γ was higher than that of CD4 + T cells, while the proportion of CD4 + and CD8 + T cells secreting IL-17A was low. Conclusions:This study established a multi-color flow detection scheme that could simultaneously detect multiple cellular surface molecules and cytokines at the single cell level and could accurately and comprehensively analyze the immune cell subsets, functions and the immune checkpoint molecules in peripheral blood of Chinese rhesus macaques, providing a new experimental method and basic data for the development of vaccines and drugs against infectious diseases.