Morphological Characteristics of the Results of Experimental Modeling of Septic Peritonitis

SUMMARY: Experimental studies devoted to the study of the mechanisms of the pathogenesis of acute peritonitis and the development of new methods of medical and surgical treatment are becoming increasingly relevant. Today, experimental medicine knows many different ways to modeling septic peritonitis and eliminate it, but the role of the local immune system is underestimated, whereas it takes a direct part in inflammation. The objective of our work to study morphological features of results of experimental modeling of septic peritonitis in white rats. The study included 15 sexually mature white male rats weighing 276.75±6.56 grams. A simulation of septic peritonitis was performed by perforating the upper part of the cecum with four punctures with a G16 injection needle. As a result of the experiment, after examination of the peritoneal cavity, all 15 animals were diagnosed with omentum tamponade of perforated damage to the caecum. In 11 cases, the perforated wall of the caecum was covered by the greater omentum (73.34 %), and in the other 4 animals, tamponade was performed by one of the epididymal omentum (26.66 %). The initial stage of tamponade with the greater or epididymal omentums of a perforated caecum begins on the first day of the experiment and consists of tight interstitial consolidation between them, as well as in the invasion of blood vessels from the omentum side to the focus of infection, which ensure the delivery of the appropriate immunocompetent cells. As a result of this process, intensive lymphoid infiltrates are formed in this area, as well as the growth of adipose tissue, which isolates the inflammatory focus from the peritoneal cavity with a thick layer.

Las investigaciones experimentales dedicadas al estudio de los mecanismos de patogénesis de la peritonitis aguda y el desarrollo de nuevos métodos de tratamiento médico y quirúrgico son cada vez más relevantes. Hoy en día, la medicina experimental conoce muchas formas diferentes de modelar la peritonitis séptica y eliminarla, pero se subestima el papel del sistema inmunológico local, mientras que él participa directamente en la inflamación. El objetivo de nuestro trabajo fue estudiar las características morfológicas de los resultados del modelado experimental de peritonitis séptica en ratas blancas. El estudio incluyó 15 ratas macho blancas, sexualmente maduras que pesaban 276,75 ± 6,56 gramos. Se realizó una simulación de peritonitis séptica perforando la parte superior del ciego con cuatro punciones con una aguja de inyección G16. Como resultado del experimento, después del examen de la cavidad peritoneal, a los 15 animales se les diagnosticó taponamiento del omento o lesión perforada del ciego. En 11 casos, la pared perforada del ciego fue recubierta por el omento mayor (73,34 %), y en los otros 4 animales el taponamiento se realizó por uno de los epidídimos (26,66 %). La etapa inicial del taponamiento con omento mayor o epidídimo de un ciego perforado comienza el primer día del experimento y consiste en una estrecha consolidación intersticial entre ellos, así como en la invasión de los vasos sanguíneos desde el lado del omento hasta el foco de infección, que aseguran la entrega de las células inmunocompetentes apropiadas. Como resultado de este proceso, se forman intensos infiltrados linfoides en esta zona, así como el crecimiento de tejido adiposo, que aísla el foco inflamatorio de la cavidad peritoneal con una gruesa capa.

METTL3-mediated HPV vaccine enhances the effect of anti PD-1 immunotherapy to alleviate the development of cutaneous squamous cell carcinoma

Abstract Background Cutaneous squamous cell carcinoma (cSCC) develops from epithelial keratinocytes by dysregulation of self-renewal and differentiation. Recent studies have found that the size and number of cSCC tumors gradually decrease or even disappear after HPV vaccination. However, the role of the HPV vaccine in the cSCC mechanism is poorly understood. Objective The aim of this study is to investigate the effect and mechanism of the HPV vaccine in cSCC. Methods Immunofluorescence was used to study the immune infiltrating cells in the tumor tissues of patients with cSCC. The effects of the HPV vaccine on cSCC cells and tissues were studied by Cell Culture, Real-time PCR, Western Blot, Cytotoxicity Assay, Enzyme-linked Immunosorbent Assay, m6A Blotting, CCK-8 Assay, m6A Ribonucleic acid Methylation Quantification and tumor transplantation. Results The HPV vaccine enhanced the toxic effect of CD8+T cells on cSCC cells and promoted the secretion of multiple cytokines by CD8+T cells. In addition, HPV vaccines can increase tumor sensitivity to anti-PD-1 therapy by downregulating METTL3 in tumor tissue, with the combination of HPV vaccine and PD-1 monoclonal antibodies producing enhanced immune cell infiltration compared to PD-1 blockade alone. Study limitations It is important to note the limitations of this study, including the small sample size, the construction of the mouse model, and the choice of HPV vaccine and PD-1 monoclonal antibody, which may limit the generalization of our findings to a wider population. Conclusions It is hoped that this research will contribute to a deeper understanding of the role of the HPV vaccine in the treatment of cSCC. HPV vaccine is expected to become an important approach to alleviate the development of cSCC.

Deficiency in infiltration of CD8/CD3 positive lymphocytes and macrophages plays a role in lip carcinogenesis: an immunohistochemical study

Abstract Objective To evaluate the immunoexpression profile for CD8, CD3, CD20 and CD68 in the process and carcinogenesis of Carcinoma of the vermilion lip. Methods Average cell count with positive expression for CD3, CD8, CD20 and CD68. The CD8/CD3 ratio calculated in the region was based on the percentage of positive cells in a total of malignant cells. Kruska-Wallis/Dunn, Mann-Whitney and Spearman correlation tests (SPSS, p< 0.05) were used. Results In the Aquitic Cheilitis samples, there was an increase in intraepithelial CD8+ and CD68+. In LSCCs, there was an increase in peritumoral and intratumoral CD3+, CD8+, CD20+ and CD68+ cells. In peritumoral LSCC, CD3+ and CD8+ showed a direct correlation (p= 0.004), and CD68+ and CD8+ (p= 0.017). In the intraepithelial region, CD8+ correlated with CD20+ (p= 0.014) and CD68+ (p= 0.013). In the CAs, CD3 (p< 0.001) and CD8 (p= 0.025) correlated intraepithelial and subepithelial. In LSCC CD3+ (p= 0.002), CD8+ (p= 0.001) and CD68+ (p= 0.030) had intra and peritumoral correlation. Conclusion CD68+ is the first interacting cell with the greatest capacity to migrate to the tumor and interact with CD3, CD8 and CD20. Apparently, CD20 affects perineural invasion. Level of evidence: Level 2.

Safety of the yellow fever vaccine in people living with HIV: a longitudinal study exploring post-vaccination viremia and hematological and liver kinetics

ABSTRACT Background: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]. Methods: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5. Results: A total of 202 PLWH with CD4 > 200 cells/μL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia. Conclusions: 17DD was safe and well-tolerated in PLWH with CD4 > 200 cells/μL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination.

Humoral and Cellular Immunology in Human Prostate Cancer: Plasma Cells and T and B Lymphocytes / Inmunología Humoral y Celular en el Cáncer de Próstata Humano: Células Plasmáticas y Linfocitos T y B

SUMMARY: In solid and malignant tumors, innate and adaptive immunity are combined in antitumor responses. This study aimed to analyze the activation of plasma cells and the correlation between the infiltration of B and T lymphocytes with the degree of malignancy or Gleason grade in human prostate biopsies diagnosed with cancer. Prostate cancer biopsies were obtained from the Clinical Hospital of Universidad de Chile (n=70), according to the bioethical norms of the institution. Histological sections of 5µm thickness were processed for immunohistochemistry with primary antibodies against BL and total TL (HRP/DAB). Recognition and quantification were performed under a Leica DM750 optical microscope. Microsoft Excel and GraphPad software were used for the statistical study. Correlation coefficient (Pearson) and mean comparison tests (Kruskal-Wallis and Dunn) and p≤ 0.05 were developed. B and T lymphocyte populations were inversely interregulated in prostate cancer (Gleason) (r= -0.46). Their relationship with Gleason grade is variable according to lymphocyte type (LB vs. Gleason r= -0.0.47 and LT vs. Gleason r= -0.21). Histological diagnosis of prostate cancer correlates with a predominance of LT. The malignancy of the pathology correlates with a predominance of LTs, according to the Gleason grade. The increased knowledge of B and T lymphocyte infiltration and plasma cell activation could be used to better target clinical trials on treatments based on immune system responses. Immunotherapy could be a new paradigm to apply better antitumor therapy strategies.

En tumores sólidos y malignos, la inmunidad innata y adaptativa se combinan en respuestas antitumorales. Este estudio tuvo como objetivo analizar la activación de células plasmáticas y la correlación entre la infiltración de linfocitos B y T con el grado de malignidad o grado de Gleason en biopsias de próstata humana diagnosticadas con cáncer. Las biopsias de cáncer de próstata se obtuvieron del Hospital Clínico de la Universidad de Chile (n=70), de acuerdo con las normas bioéticas de la institución. Secciones histológicas de 5 µm de espesor fueron procesadas para inmunohistoquímica con anticuerpos primarios contra LB y LT total (HRP/DAB). El reconocimiento y las cuantificaciones se realizaron bajo un microscopio óptico Leica DM750. Para el estudio estadístico se utilizaron los programas Microsoft Excel y GraphPad. Se desarrollaron pruebas de coeficiente de correlación (Pearson) y comparación de medias (Kruskal-Wallis y Dunn) y p≤ 0.05. Los resultados muestran que las poblaciones de linfocitos B y T están inversamente interreguladas en el cáncer de próstata (r= -0,4578). Su relación con el grado de Gleason es variable según el tipo de linfocito (LB vs Gleason r= -0,47* y LT vs Gleason r= -0,21). Se concluye que la malignidad del cáncer de próstata se correlaciona con un predominio de LT, versus el grado de Gleason. El mayor conocimiento de la infiltración de linfocitos B y T y la activación de células plasmáticas podría aprovecharse para una mejor orientación de ensayos clínicos en tratamientos basados en las respuestas del sistema inmunitario. La inmunoterapia podría ser un nuevo paradigma para aplicar mejores estrategias de terapias antitumorales.

Evaluation of lymphocyte count, T-cell subsets and neutrophil-to-lymphocyte ratio as early predictors for severity and outcome of COVID-19 disease-a report from a highly complex hospital in Brazil

ABSTRACT Introduction: Lymphopenia is a laboratory marker of poor prognosis and severity of disease in the SARS-CoV-2 infection. This study aims to describe the immune profile of a Brazilian population. Methods: A total of 121 consecutive patients with severe acute respiratory syndrome (SARS) were analyzed between April and June 2020. Routine peripheral blood counts and multiparametric flow cytometry were performed on admission to assess lymphocytes and subsets (CD3, CD4, CD8). Demographic, clinical and laboratory data were collected from hospital sources. Results: The total of 116 patients included 63 (54.3%) males; 76 (62.8%) COVID-19 patients were divided, based on clinical characteristics and mechanical ventilation (MV) use, into moderate (n = 41; no MV) and severe (n = 35; MV) groups. The control group (n = 40) was comprised of patients with SARS of different etiologies. All patients had lymphopenia, with overall lymphocyte counts and their subsets considerably lower in severe patients, when compared to the moderate and controls. Patients with a high neutrophil-to-lymphocyte ratio (> 15.2) and T-cell lymphopenia (CD3 < 593 cells/μL, CD4 < 326 cells/μL, CD8 < 121 cells/μL) had a higher risk of being intubated and progressing to death. A total of 39 patients (95.1%) in the moderate group and 54.3% (n = 19) in the severe group were discharged; 28 patients died. Conclusion: Laboratory assessment of the neutrophil/lymphocyte ratio and T-cell subsets may be predictive of mortality and may be useful for stratifying COVID-19 patients.

Programmed cell death protein 1 is a marker for neoadjuvant chemotherapy response in triple-negative breast cancer

SUMMARY OBJECTIVE: Tumor-infiltrating lymphocytes are detectable in up to 75% of triple-negative breast cancer. The composition of these infiltrates may influence prognosis and is not known regarding regulatory or effector lymphocytes. The objectives of this study were to describe and quantify the composition of the tumor-infiltrating lymphocytes before and after chemotherapy (neoadjuvant chemotherapy) and to evaluate their association with complete pathological response and overall survival. METHODS: This was a retrospective observational study. Clinical and pathological data from 38 triple-negative breast cancer patients treated with neoadjuvant chemotherapy at the University Hospital (HUCFF/UFRJ), between November 2004 and November 2018, were analyzed. The Stromal tumor-infiltrating lymphocytes (Stromal tumor-infiltrating lymphocytes) have been identified on hematoxylin and eosin-stained sections according to the guidelines of the "International tumor-infiltrating lymphocytes Working Group." Immunohistochemistry studies were performed to identify T-cell subsets (i.e., CD3, CD4, CD8, and FOXP3) and T-cell exhaustion (i.e., programmed cell death protein 1). RESULTS: Statistically significant changes in stromal tumor-infiltrating lymphocyte categories were observed before and post-neoadjuvant chemotherapy, with 32% of intermediate cases becoming high. The correlation between pre-neoadjuvant chemotherapy stromal tumor-infiltrating lymphocytes and pathological response, pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy, and stromal tumor-infiltrating lymphocytes and overall survival was not statistically significant. However, we noticed an increase of cells that favor the antitumor activity (i.e., CD3, CD8, and CD8/FOXP3 ratio) and decreased levels of cells inhibiting tumor activities (i.e., FOXP3 and programmed cell death protein 1) post-neoadjuvant chemotherapy. Importantly, programmed cell death protein 1 expression pre-neoadjuvant chemotherapy showed an association with pathological response. CONCLUSION: In this study, we observed that chemotherapy significantly increases stromal tumor-infiltrating lymphocytes, CD8 T cells, as well as CD8/FoxP3 ratio. Most importantly, programmed cell death protein 1 expression before neoadjuvant chemotherapy positively correlates with pathological response suggesting the use of programmed cell death protein 1 as a prognostic marker before neoadjuvant chemotherapy.

Linfocitopenia como biomarcador de gravedad en pacientes pediátricos con la COVID-19

Introducción: La COVID-19 en edades pediátricas presenta características singulares; un pequeño número de pacientes pediátricos desarrollan un estado clínico grave. Objetivos: Evaluar si la linfocitopenia es un predictor de gravedad en pacientes pediátricos con la COVID-19. Métodos: Se estudiaron en 706 pacientes, las variables edad, sexo, antecedentes patológicos personales de enfermedades crónicas de la infancia (asma bronquial, diabetes mellitus), comorbilidades, estado clínico, valores de linfocitos, conteo absoluto de linfocitos (≤ 1 x 109/L = linfocitopenia). De acuerdo con el estado clínico los pacientes se agruparon en 5 grupos, de asintomáticos a críticos. Se determinó la correlación entre el estado clínico y el conteo absoluto de linfocitos; de este se determinó su capacidad discriminativa para estimar el pronóstico. Resultados: La media de la edad fue 8,6 años; el 6,2 % de los pacientes evolucionó al estado grave o crítico; 74,6 % tuvo valores normales de linfocitos, el 16,14 % altos y el 9,2 % bajos. Linfocitopenia presentó el 4,2 %; se correlacionó significativamente con estado grave, área bajo la curva de 0,711 (IC 95 %: 0,595-0,827); 46 % de sensibilidad y 98 % de especificidad. Conclusiones: La linfocitopenia es un biomarcador que puede estimar el pronóstico en pacientes pediátricos con la COVID-19 que desarrollan un estado clínico grave.

Introduction: COVID-19 in pediatric ages presents unique features; a small number of pediatric patients develop severe clinical status. Objectives: To evaluate whether lymphocytopenia is a predictor of severity in pediatric patients with COVID-19. Methods: In 706 patients were studied the variables age, sex, personal pathological history of childhood chronic diseases (bronchial asthma, diabetes mellitus), comorbidities, clinical status, lymphocyte values, absolute lymphocyte count (≤ 1 x 109/L = lymphocytopenia). According to clinical status patients were grouped into 5 groups, from asymptomatic to critical. The correlation between clinical status and absolute lymphocyte count was determined; its discriminative capacity to estimate prognosis was determined. Results: The mean age was 8.6 years; 6.2% of patients progressed to severe or critical condition; 74.6% had normal lymphocyte values, 16.14% high and 9.2% low. Lymphocytopenia presented 4.2%; it was significantly correlated with severe condition, area under the curve of 0.711 (95% CI: 0.595-0.827); 46% sensitivity and 98% specificity. Conclusions: Lymphocytopenia is a biomarker that can estimate prognosis in pediatric patients with COVID-19 who develop severe clinical status.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and prognosis after aneurysmal subarachnoid hemorrhage: a cohort study / Razão neutrófilos-linfócitos e razão plaquetas-linfócitos e o prognóstico de hemorragia subaracnóidea aneurismática: um estudo de coorte

Abstract Background Subarachnoid hemorrhage (SAH) prognosis remains poor. Vasospasm mechanism might be associated with inflammation. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been studied as inflammation markers and prognostic predictors. Objective We aimed to investigate NLR and PLR in admission as predictors of angiographic vasospasm and functional outcome at 6 months. Methods This cohort study included consecutive aneurysmal SAH patients admitted to a tertiary center. Complete blood count was recorded at admission before treatment. White blood cell count, neutrophil count, lymphocyte count, platelet count, NLR, and PLR were collected as independent variables. Vasospasm occurrence-modified Rankin scale (mRS), Glasgow outcome scale (GOS), and Hunt-Hess score at admission and at 6 months were recorded as dependent variables. Multivariable logistic regression models were used to adjust for potential confounding and to assess the independent prognostic value of NLR and PLR at admission. Results A total of 74.1% of the patients were female, with mean age of 55.6 ± 12.4 years. At admission, the median Hunt-Hess score was 2 (interquartile range [IQR] 1), and the median mFisher was 3 (IQR 1). Microsurgical clipping was the treatment for 66.2% of the patients. Angiographic vasospasm incidence was 16.5%. At 6 months, the median GOS was 4 (IQR 0.75), and the median mRS was 3 (IQR 1.5). Twenty-one patients (15.1%) died. Neutrophil-to-lymphocyte ratio and PLR levels did not differ between favorable and unfavorable (mRS > 2 or GOS < 4) functional outcomes. No variables were significantly associated with angiographic vasospasm. Conclusion Admission NLR and PLR presented no value for prediction of functional outcome or angiographic vasospasm risk. Further research is needed in this field.

Resumo Antecedentes O prognóstico da hemorragia subaracnoidea (HSA) permanece ruim. Vasoespasmo pode estar associado à inflamação. Razões neutrófilo-linfócito (NLR) e plaqueta-linfócito (PLR) têm sido estudadas como marcadores de inflamação e prognóstico. Objetivo Investigar NLR e PLR na admissão como preditores de vasoespasmo angiográfico e desfecho aos 6 meses. Métodos Este estudo de coorte incluiu pacientes consecutivos com HSA aneurismática de um centro terciário. Contagem de leucócitos, neutrófilos, linfócitos e plaquetas, proporção de neutrófilos para linfócitos e de plaquetas para linfócitos foram coletados como variáveis independentes. Ocorrência de vasoespasmo, escala de Rankin modificada, escala de desfecho de Glasgow e o escore de Hunt-Hess na admissão e 6 meses após a mesma foram registradas como variáveis dependentes. Modelos de regressão logística multivariável foram usados para ajustar potenciais fatores de confusão e avaliar valor prognóstico independente de NLR e PLR. Resultados Um total de 74,1% pacientes eram do sexo feminino, com idade média de 55,6 ± 12,4 anos. Na admissão, a pontuação média de Hunt-Hess foi de 2 (IQR 1) e a mediana de mFisher foi de 3 (IQR 1). Clipagem microcirúrgica foi o tratamento escolhido para 66,2% dos pacientes. A incidência de vasoespasmo angiográfico foi de 16,5%. Aos 6 meses, a escala de desfecho de Glasgow mediana era 4 (IQR 0,75) e a escala de Rankin modificada mediana era 3 (IQR 1,5). Vinte e um pacientes (15,1%) morreram. Os níveis de NLR e PLR não diferiram entre resultados funcionais favoráveis e desfavoráveis (mRS > 2 ou GOS < 4). Nenhuma variável foi significativamente associada ao vasoespasmo angiográfico. Conclusão Razão neutrófilo-linfócito e a PLR não apresentaram valor preditivo de desfecho funcional ou risco de vasoespasmo angiográfico. Mais pesquisas são necessárias neste campo.

Inflammation in Cardiovascular Disease: Current Status and Future Perspectives

Abstract Atherosclerosis has been defined as an inflammatory disease. Three decades of research have pointed to a pivotal role of interleukin 6 for many aspects of cardiovascular disease, not the least of which is atherosclerosis. In this review, experimental and clinical studies are reported on a timeline, exploring mechanisms and possible explanations that form the basis of current knowledge. Some successful clinical trials were proof of concept studies, showing that not only inflammatory biomarkers are related to cardiovascular outcomes, but also that decreasing inflammation can reduce cardiovascular events. Great advances have been made in the management of residual cardiovascular risk due to cholesterol, thrombosis, and metabolic diseases, but the next frontier now seems to be targeting inflammation. In the upcoming years, the importance of inflammation will be evaluated in high-risk patients with chronic kidney disease, after acute coronary heart disease or heart failure with preserved ejection fraction. Inflammation seems to precede the development of cardiovascular risk factors. Moreover, counseling for a heathy lifestyle and, when necessary, the use of cardiometabolic therapies capable of decreasing inflammation, might be important.

Efecto de la inmunidad celular en el tratamiento de las úlceras del pie diabético con Heberprot-P® / Effect of cellular immunity in the treatment of diabetic foot ulcers with Heberprot-P®

Introducción: Los diabéticos muestran una disminuida función del sistema inmune. Su complicación más temida es la aparición de las úlceras del pie. El Heberprot-P® tiene efectos beneficiosos en la curación de estas úlceras. Objetivo: Evaluar el efecto de la inmunidad celular en el tratamiento de las úlceras del pie diabético con Heberprot-P®. Métodos: Se realizó un estudio observacional, prospectivo, de serie de casos, en 30 pacientes con úlcera de pie diabético, ingresados en el Instituto Nacional de Angiología y Cirugía Vascular. Se administraron 75 µg de Heberprot-P®, tres veces por semana, a través de vías peri- e intralesional, durante ocho semanas. Se evaluaron las variables edad, sexo, glucemia en ayunas, creatinina, urea, ácido úrico, prueba de hipersensibilidad retardada, porcentaje de granulación, tiempo de cierre de la lesión y localización de la úlcera, antes de comenzar el tratamiento, a las 4 y 8 semanas. Resultados: Se precisó un predominio del 60 por ciento en el sexo femenino y del color de piel blanca. Los niveles de glucemia y creatinina se comportaron más elevados en los anérgicos; la urea fue similar tanto en anérgicos como en reactivos; y el ácido úrico resultó mayor en hombres reactivos y en mujeres anérgicas. Hubo mayor proporción de reactivos (63,6 por ciento), que en la cuarta semana presentaron un tejido de granulación igual o mayor al 50 por ciento; y a la octava, igual o mayor al 70 por ciento. Conclusiones: La condición en los pacientes diabéticos de ser reactivo a las pruebas de hipersensibilidad retardada con úlcera de pie diabético de tipo neuropática, tratados con Heberprot-P®, está asociada directamente con una mejor respuesta en la cicatrización de sus lesiones, mediante la formación del tejido de granulación, que favorece el cierre total o parcial de la lesión. Esto no ocurrió con los pacientes anérgicos a dicha prueba(AU)

Introduction: Diabetics show decreased immune system function. Its most feared complication is the appearance of foot ulcers. Heberprot-P® has beneficial effects in healing these ulcers. Objective: To assess the effect of cellular immunity in the treatment of diabetic foot ulcers with Heberprot-P®. Methods: An observational, prospective, case series study was conducted in 30 patients with diabetic foot ulcer admitted to the National Institute of Angiology and Vascular Surgery. 75 µg of Heberprot-P®, three times a week, were administered through peri- and intralesional routes, during eight weeks. The variables age, sex, fasting blood glucose, creatinine, urea, uric acid, delayed hypersensitivity test, percentage of granulation, time of closure of the lesion and location of the ulcer, before starting treatment, at 4 and 8 weeks were evaluated. Results: A predominance of 60 % in females and white skin color were specified. Blood glucose and creatinine levels behaved higher in the anergics; urea was similar in both anergics and reagents; and uric acid was higher in reactive men and anergic women. There was a higher proportion of reagents (63.6 por ciento), which in the fourth week presented a granulation tissue equal to or greater than 50 por ciento; and at the eighth week, it was equal to or greater than 70 por ciento. Conclusions: The condition of being reactive to delayed hypersensitivity tests in diabetic patients with diabetic foot ulcer of neuropathic type, treated with Heberprot-P® is directly associated with a better response in the healing of their lesions, through the formation of granulation tissue, which favors the total or partial closure of the lesion. This did not occur with patients who were anergic to this test(AU)

TTYH3 is a prognostic biomarker and associates with immune cell infiltrations of lung adenocarcinoma / TTYH3 es un biomarcador pronóstico y se asocia con infiltraciones de células inmunitarias del adenocarcinoma de pulmón

SUMMARY: We investigated Tweety Family Member 3 (TTYH3) level in lung adenocarcinoma (LUAD) and its relationship with immune infiltration in tumors by bioinformatics. Differential expressions of TTYH3 in lung cancer were analyzed with Oncomine, TIMER, GEO, UALCAN and HPA. Relationship of TTYH3 mRNA/protein levels with clinical parameters was analyzed by UALCAN. Co-expressed genes of TTYH3 in LUAD were analyzed using Cbioportal. Its relationship with LUAD prognosis was analyzed by Kaplan-Meier plotter. GO and KEGG analysis were performed. Correlation between TTYH3 and tumor immune infiltration were tested by TIMER, TISIDB and GEPIA. We found that TTYH3 was significantly increased in LUAD tissues. TTYH3 high expression was closely related to poor overall survival, post progression survival and first progression in LUAD patients. TTYH3 mRNA/protein levels were significantly associated with multiple pathways. Specifically, TTYH3 up-regulation was mostly related to biological regulation, metabolic process, protein blinding, extracellular matrix organization and pathways in cancer. Moreover, TTYH3 was positively associated with immune cell infiltration in LUAD. Finally, TTYH3 was highly expressed in LUAD as revealed by meta-analysis. TTYH3 is closely related to the prognosis of LUAD and immune cell infiltration, and it can be used as a prognostic biomarker for LUAD and immune infiltration.

Investigamos por bioinformática el nivel de Tweety Family Member 3 (TTYH3) con adenocarcinoma de pulmón (LUAD) y su relación con la infiltración inmune en tumores. Las expresiones diferenciales de TTYH3 en cáncer de pulmón se analizaron con Oncomine, TIMER, GEO, UALCAN y HPA. Con UALCAN se analizó la relación de los niveles de ARNm/proteína de TTYH3 con los parámetros clínicos. Los genes coexpresados de TTYH3 en LUAD se analizaron utilizando Cbioportal. Su relación con el pronóstico LUAD se analizó mediante plotter de Kaplan- Meier. Se realizaron análisis GO y KEGG. TIMER, TISIDB y GEPIA probaron la correlación entre TTYH3 y la infiltración inmune tumoral. Encontramos que TTYH3 aumentó significativamente en los tejidos LUAD. La alta expresión de TTYH3 estuvo estrechamente relacionada con una supervivencia general deficiente, supervivencia posterior a la progresión y primera progresión en pacientes con LUAD. Los niveles de ARNm/ proteína de TTYH3 se asociaron significativamente con múltiples vías. Específicamente, la regulación positiva de TTYH3 se relacionó principalmente con la regulación biológica, el proceso metabólico, el cegamiento de proteínas, la organización de la matriz extracelular y las vías en el cáncer. Además, TTYH3 se asoció positivamente con la infiltración de células inmunitarias en LUAD. Finalmente, TTYH3 se expresó altamente en LUAD como lo reveló el metanálisis. TTYH3 está estrechamente relacionado con el pronóstico de LUAD y la infiltración de células inmunitarias, y se puede utilizar como biomarcador pronóstico para LUAD y la infiltración de células inmunitarias.

Linfoma em cão da raça cane corso: relato de caso / Lymphoma in a cane corso dog: case report / Linfoma en un perro cane corso: relato de un caso

Os linfócitos são células de defesa do organismo que funcionam como barreira contra infecções e células cancerígenas, elas circulam pelo sistema linfático e estão presentes por todo o organismo do animal, podem se proliferar de forma maligna, caracterizando o linfoma. Acometem em sua maioria, cães de raças de grande porte, animais de meia idade e idosos. Sendo uma doença de etiologia desconhecida, vários fatores podem contribuir para sua evolução, como deficiências autoimunes, bem como hábitos alimentares ao longo da vida do animal, ou até por predisposição genética. O presente relato de caso, tem o objetivo de mostrar a evolução gradual da doença, quais sinais clínicos o animal poderá apresentar, e como os exames laboratoriais podem nos auxiliar em seu diagnóstico.(AU)

The lymphocytes are defense cells of the body that act as a barrier against infection and cancer cells, they circulate through the lymphatic system and are present throughout the animal's body, and can proliferate in a malignant way, characterizing the lymphoma. They mostly affect large breed dogs, middle-aged and elderly animals. Being a disease of unknown etiology, several factors may contribute to its evolution, such as autoimmune deficiencies, as well as food habits throughout the animal's life, or even genetic predisposition. The present case report has the objective of showing the gradual evolution of the disease, which clinical signs the animal may present, and how laboratory tests can help us in its diagnosis.(AU)

Los linfocitos son células de defensa del organismo que actúan como barrera contra infecciones y células cancerígenas, circulan por el sistema linfático y están presentes en todo el organismo del animal, pudiendo proliferar de forma maligna, caracterizando el linfoma. Afectan sobre todo a perros de razas grandes, animales de mediana edad y ancianos. Siendo una enfermedad de etiología desconocida, varios factores pueden contribuir a su evolución, como deficiencias autoinmunes, así como hábitos alimentarios a lo largo de la vida del animal, o incluso predisposición genética. El presente caso clínico tiene como objetivo mostrar la evolución gradual de la enfermedad, qué signos clínicos puede presentar el animal y cómo las pruebas de laboratorio pueden ayudarnos en su diagnóstico.(AU)

Investigation on the incidence of IRIS in HIV patients with TB infection and its relationship with Th17/Treg, CD4 + T lymphocyte levels / 中国医师杂志

Objective:To investigate the incidence of immune reconstitution inflammatory syndrome (IRIS) in patients with HIV (HIV) and tuberculosis (TB) infection, and analyze the relationship between Th17/Treg cytokines, CD4 + T lymphocytes and IRIS. Methods:HIV patients with TB infection admitted to Public Health Clinical Center of Chengdu from June 2020 to June 2022 were divided into IRIS group (31 cases) and non IRIS group (93 cases) according to whether IRIS occurred after highly active antiretroviral therapy (HAART). The Demography data, clinical data and laboratory indicators of the two groups were compared. Multivariate logistic regression analysis was conducted to investigate the influencing factors of IRIS in HIV patients with TB infection.Results:There was no significant difference in Demography data between the two groups ( P>0.05). There was a statistically significant difference in the history of opportunistic infection between the IRIS group and the non IRIS group (χ 2=5.194, P<0.05). The levels of HIV RNA, interleukin (IL)-17, and IL-23 in the IRIS group were higher than those in the non IRIS group (all P<0.05). The levels of the γ interferon (IFN- γ), the transforming growth factor-β (TGF- β) and baseline CD4 + T lymphocyte count were lower than those in the non IRIS group (all P<0.05). The results of multivariate logistic regression analysis showed that IL-17 ( OR: 1.266, 95% CI: 1.095-1.464), IL-23( OR: 1.384, 95% CI: 1.120-1.710), and TGF- β( OR: 0.589, 95% CI: 0.436-0.797) were influencing factors for the occurrence of IRIS in HIV patients with TB infection (all P<0.05). Conclusions:For patients with high IL-17 levels, high IL-23 levels, and low TGF- β level of HIV complicated with TB infection, clinical prevention and control should be carried out as soon as possible to prevent the occurrence of IRIS.

The relationship of RDW-SD, NLR and FIB with the prognosis of multiple myeloma patients and their predictive value / 中国医师杂志

Objective:To explore the relationship between the standard deviation of red blood cell distribution width (RDW-SD), neutrophil/lymphocyte value (NLR), fibrinogen (FIB) and the prognosis of multiple myeloma (MM) patients and their predictive value.Methods:In this study, a retrospective study method was used to select 120 patients with MM who were initially diagnosed in the department of hematology of the Affiliated Hospital of Jining Medical College from January 2017 to October 2019. The follow-up time was 24 months, including 62 patients who survived (survival group) and 58 patients who died (death group). The RDW-SD, NLR and FIB values of the two groups were compared, and the value of the three indicators in predicting the follow-up outcome of MM patients was analyzed using the receiver operating characteristic (ROC) curve. Logistic regression model was used to analyze the related factors affecting the prognosis of MM patients.Results:Among 120 newly treated MM patients, the RDW-SD, NLR and FIB of the survival group were significantly lower than those of the death group (all P<0.05); The sensitivity, specificity and area under ROC curve (AUC) of RDW-SD+ NLR+ FIB in predicting adverse outcomes of MM patients were 88.96%, 84.50% and 0.919 respectively. Logistic multivariate regression analysis showed that ≥60 years old, International Staging System (ISS) Ⅲ, β2-microglobulin (β2-MG)≥3 500 ng/ml, increased RDW-SD, NLR, and FIB will increase the risk of poor prognosis in MM patients (all P<0.05). Conclusions:The RDW-SD, NLR and FIB have a close relationship with the poor prognosis of newly treated MM patients, and the combined application has certain value in predicting the prognosis of patients.

Diagnostic analysis of cTTE for patent foramen ovale and the value of combined NLR monitoring in predicting cryptogenic stroke / 中国医师杂志

Objective:To investigate the diagnostic value of transthoracic echocardiographic contrast-enhanced ultrasound (cTTE) in patent foramen ovale (PFO) and the value of combined neutrophil to lymphocyte ratio (NLR) in predicting cryptogenic stroke.Methods:A total of 120 suspected PFO patients admitted to the Affiliated Hospital of Jining Medical College from January 2021 to December 2021 were selected and examined by cTTE and transesophageal echocardiography (TEE) to analyze the diagnostic value of cTTE in PFO. The clinical data and cTTE parameters of PFO patients with and without cryptogenic stroke were analyzed.Results:A total of 69 patients with PFO were confirmed. Among the 69 patients, 23 patients with cryptogenic stroke and 46 patients without cryptogenic stroke were confirmed by magnetic resonance imaging (MRI). The value of cTTE in the diagnosis of PFO was high: the sensitivity, accuracy and negative predictive value of cTTE under Valsalva motion in the diagnosis of PFO were 95.65%, 91.67% and 93.62%, respectively, which were significantly higher than that of cTTE at rest (all P<0.05). The NLR, the proportion of large shunt of PFO right to left shunt (PFO-RLS), the inlet width of patent foramen ovale (PFO) and the outlet width of PFO in patients with PFO complicated with cryptogenic stroke were (3.01±0.89), 43.48%(10/23), (2.54±0.65)mm and (1.51±0.35)mm, respectively, which were significantly higher than those in patients without cryptogenic stroke (all P<0.05). Logistic regression analysis showed that NLR and the degree of PFO-RLS shunt were the influencing factors of patients with PFO complicated with cryptogenic stroke (both P<0.05). The area under the Receiver operating characteristic (ROC) curve predicted by NLR combined with PFO-RLS shunt was 0.905, which was significantly higher than that predicted by NLR and PFO-RLS shunt alone (all P<0.05). Conclusions:cTTE has a good value in the diagnosis of PFO, and cTTE combined with NLR has a certain application value in predicting PFO complicated with cryptogenic stroke.

Influencing factors of severe pneumonia in children with respiratory syncytial virus infection / 中国医师杂志

Objective:To explore the influencing factors of severe pneumonia in children with respiratory syncytial virus (RSV) infection.Methods:A retrospective case-control study was used to collect 210 children with RSV infected pneumonia admitted to Hebei Children′s Hospital from October 2017 to October 2020. Among them, 70 children with severe pneumonia were included in the severe pneumonia group, and 140 children with common pneumonia were included in the common pneumonia group; the baseline data and relevant laboratory indicators of the two groups were compared; Logistic regression was used to analyze the influencing factors of severe pneumonia in children infected with RSV.Results:The proportions of wheezing, congenital heart disease, respiratory failure, heart failure and pleural effusion of children in severe pneumonia group were higher than those in common pneumonia group, and the forced vital capacity (FVC) and forced expiratory volume in the first second (FEV 1) were lower than those in common pneumonia group (all P<0.05); the levels of C-reactive protein (CRP), CD8 + cells, RSV load and Beclin-1 in severe pneumonia group were higher than those in common pneumonia group, and the levels of CD4 + cells and 1, 25-dihydroxyvitamin D [1, 25-(OH) 2D] were lower than those in common pneumonia group (all P<0.05). After treatment, the levels of CRP, CD8 + cells and Beclin-1 in children with severe pneumonia were lower than those before treatment, and the levels of CD4 + cells and 1, 25-(OH) 2D were higher than those before treatment (all P<0.05). Multiple regression model analysis was established. The results showed that congenital heart disease, high CRP level, high CD8 + cells, high RSV load and high Beclin-1 level were risk factors for severe pneumonia in children with RSV infected pneumonia (all OR>1, P<0.05), and high CD4 + cells and 1, 25-(OH) 2D level were protective factors (all OR<1, P<0.05). Conclusions:Severe pneumonia in children with RSV infected pneumonia may be affected by congenital heart disease, CRP, CD4 + cells, CD8 + cells, 1, 25-(OH) 2D, RSV load and Beclin-1.

The relationship between albumin, erythrocyte sedimentation rate, platelet/lymphocyte ratio, neutrophil/lymphocyte ratio and the degree of coronary artery disease in children with Kawasaki disease / 中国医师杂志

Objective:To explore the relationship between serum albumin (ALB), erythrocyte sedimentation rate (ESR), platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR) and coronary artery disease in children with Kawasaki disease (KD).Methods:120 KD children diagnosed in the Affiliated Hospital of Jining Medical College from December 2016 to November 2021 were selected as the research objects. They were divided into observation group (KD with coronary artery disease) and control group (KD with coronary artery disease) according to whether they had coronary artery disease, with 60 cases in each group; the serum ALB, ESR, PLR, NLR values of the two groups of children were compared. Receiver operating characteristic (ROC) curve was used to analyze the value of the above indicators in diagnosing KD children with coronary artery disease. The serum ALB, ESR, PLR, NLR levels of KD children with different degrees of coronary artery disease were analyzed.Results:The main manifestations of coronary artery disease in 60 children with KD combined with coronary artery disease were left main coronary artery and left anterior descending branch widening [56.67%(34/60)], left main coronary artery and left anterior descending branch widening [20.00%(12/60)], left anterior descending branch widening [16.67%(10/60)], left main coronary artery widening [11.67%(7/60)]. The serum ALB in the observation group was significantly lower than that in the control group ( P<0.05), and ESR was significantly higher than that in the control group ( P<0.05). There was no significant difference in serum PLR and NLR between observation group and control group (all P>0.05). The sensitivity, specificity and area under curve (AUC) value of serum ALB in diagnosing coronary artery disease in KD children were 73.61%, 78.42% and 0.813 respectively; The sensitivity, specificity and AUC of ESR in diagnosing coronary artery disease in KD children were 88.36%, 83.14% and 0.892 respectively; The sensitivity, specificity and AUC value of ESR combined with ALB in diagnosing coronary artery disease in KD children were 90.67%, 97.54% and 0.953 respectively. Among 60 children with KD complicated with coronary artery disease, 39 were diagnosed as coronary artery dilatation and 21 had coronary artery aneurysm. The serum ALB of children in the coronary artery aneurysm group was significantly lower than that in the coronary artery dilatation group ( P<0.05), and ESR was significantly higher than that in the coronary artery dilatation group ( P<0.05). There was no significant difference in PLR and NLR between the coronary artery aneurysm group and the coronary artery dilatation group (all P>0.05). Conclusions:Children with KD and coronary artery disease have lower serum ALB levels and higher ESR level. The above two indicators are of great value for the diagnosis of children with KD and coronary artery disease.

Risk factors of drug resistance in diabetes mellitus complicated by pulmonary tuberculosis / 中国基层医药

Objective:To investigate the risk factors of diabetes mellitus complicated by pulmonary tuberculosis.Methods:The clinical data of 83 patients with diabetes mellitus complicated by pulmonary tuberculosis who received treatment in Taiyuan Fourth People's Hospital from March 2020 to March 2022 were collected. These patients were divided into sensitive group ( n = 45) and resistant group ( n = 38 ) according to the results of drug sensitivity test. Univariate and multivariate non-conditional logistic regression was performed to analyze the influential factors of drug resistance. Results:Univariate logistic regression results revealed that there were significant differences in blood CD4 +T lymphocyte count ( χ2 = 11.73, P = 0.001) and diabetic complications ( χ2 = 4.94, P = 0.026). Multivariate non-conditional logistic regression analysis was performed taking whether blood CD4 +T lymphocyte count was lower than the average level and whether patients with diabetes mellitus had complications as independent variables, and taking whether drug resistance was a dependent variable. The results showed that the OR (95% CI) value of the decreased blood CD4 +T lymphocyte count was 4.909 (1.926-12.514). It is a risk factor for drug resistance of diabetes mellitus complicated by pulmonary tuberculosis. Conclusion:The decrease of blood CD4 +T lymphocyte count is a risk factor of drug resistance in diabetes mellitus complicated by pulmonary tuberculosis, and it should be intervened early in the clinic.

Efficacy of Zhibitai capsules combined with low-dose atorvastatin in the treatment of cervical arteriosclerosis and its effects on high-sensitivity C-reactive protein and regulatory T cells in the peripheral blood / 中国基层医药

Objective:To investigate the efficacy of Zhibitai capsules combined with low-dose atorvastatin in the treatment of cervical arteriosclerosis and its effects on high-sensitivity C-reactive protein and regulatory T cells in the peripheral blood. Methods:A total of 104 patients with carotid arteriosclerosis admitted to Fenyang Hospital from January 2021 to April 2022 were retrospectively included in this study. They were divided into a control group ( n = 52) and an observation group ( n = 52) according to different treatment methods. The control group was orally given atorvastatin calcium tablets 20 mg once a day. The observation group was orally given atorvastatin calcium tablets 10 mg once a day, and Zhibitai capsules 0.24 g, one capsule in the morning and one capsule in the evening. After 8 weeks of treatment, changes in total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and regulatory T cell proportion in the peripheral blood were evaluated. Results:After treatment, high-density lipoprotein cholesterol level and regulatory T cell proportion in the observation group were (1.53 ± 0.29) mmol/L and (5.52 ± 1.38)%, respectively, which were significantly higher than (1.19 ± 0.21) mmol/L and (4.48 ± 0.86)% respectively in the control group ( t = 6.84, 4.61, both P < 0.05). Total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein levels in the observation group were (2.88 ± 0.27) mmol/L, (1.21 ± 0.15) mmol/L, (2.01 ± 0.19) mmol/L, (2.58 ± 0.43) mg/L, respectively, which were significantly lower than (3.68 ± 0.41) mmol/L, (1.33 ± 0.19) mmol/L, (2.69 ± 0.31) mmol/L, (3.70 ± 0.25) mg/L, respectively in the control group ( t = 11.75, 3.57, 12.31, 17.23, all P < 0.05). There was no significant difference in carotid plaque size pre-treatment between the two groups, but the plaque size decreased after treatment compared with before treatment. The efficacy of Zhibitai capsules combined with low-dose atorvastatin in the treatment of cervical arteriosclerosis in the observation group was superior to that in the control group ( P < 0.05). Conclusion:Oral administration of Zhibitai capsules combined with low-dose atorvastatin for the treatment of cervical arteriosclerosis is safe and has few adverse reactions. The combined therapy can decrease serum high-sensitivity C-reactive protein levels, increase the proportion of regulatory T cells in the peripheral blood, help stabilize plaques, and reduce plaque size.