GPCRs overexpression and impaired fMLP-induced functions in neutrophils from chronic kidney disease patients.

Introduction: G-protein coupled receptors (GPCRs) expressed on neutrophils regulate their mobilization from the bone marrow into the blood, their half-live in the circulation, and their pro- and anti-inflammatory activities during inflammation. Chronic kidney disease (CKD) is associated with systemic inflammatory responses, and neutrophilia is a hallmark of CKD onset and progression. Nonetheless, the role of neutrophils in CKD is currently unclear. Methods: Blood and renal tissue were collected from non-dialysis CKD (grade 3 - 5) patients to evaluate GPCR neutrophil expressions and functions in CKD development. Results: CKD patients presented a higher blood neutrophil-to-lymphocyte ratio (NLR), which was inversely correlated with the glomerular filtration rate (eGFR). A higher frequency of neutrophils expressing the senescent GPCR receptor (CXCR4) and activation markers (CD18+CD11b+CD62L+) was detected in CKD patients. Moreover, CKD neutrophils expressed higher amounts of GPCR formyl peptide receptors (FPR) 1 and 2, known as neutrophil pro- and anti-inflammatory receptors, respectively. Cytoskeletal organization, migration, and production of reactive oxygen species (ROS) by CKD neutrophils were impaired in response to the FPR1 agonist (fMLP), despite the higher expression of FPR1. In addition, CKD neutrophils presented enhanced intracellular, but reduced membrane expression of the protein Annexin A1 (AnxA1), and an impaired ability to secrete it into the extracellular compartment. Secreted and phosphorylated AnxA1 is a recognized ligand of FPR2, pivotal in anti-inflammatory and efferocytosis effects. CKD renal tissue presented a low number of neutrophils, which were AnxA1+. Conclusion: Together, these data highlight that CKD neutrophils overexpress GPCRs, which may contribute to an unbalanced aging process in the circulation, migration into inflamed tissues, and efferocytosis.

Efficacy and safety of camrelizumab combined with chemotherapy in the treatment of advanced biliary malignancy and associations between peripheral blood lymphocyte subsets and clinical outcomes.

BACKGROUND: Biliary tract cancer (BTC) is a highly heterogeneous aggressive tumor, and advanced patients have poor prognosis. This work aimed to evaluate the efficacy and safety of camrelizumab combined with chemotherapy in treating advanced BTC, and to explore predictive biomarkers for distinguishing effective population. METHODS: 183 advanced BTC patients admitted from September 2018 to September 2021 were retrospectively selected. 93 patients were treated with camrelizumab combined with chemotherapy (C+C group) and 90 patients were treated with chemotherapy alone (C group). Objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) were analyzed between two groups. Peripheral blood lymphocyte subsets were assessed by flow cytometry pre- and post-treatment. RESULTS: The mPFS (6.9 months) and mOS (12.1 months) in the C+C group were significantly longer than those in the C group, which were 5.2 months and 9.8 months respectively (HR 0.46, 95% CI 0.38-0.54, p=0.017; HR 0.39, 95% CI 0.32-0.47, p=0.033). The percentage of Total T, CD4+T, natural killer (NK) cells, lymphocyte, and CD4+/CD8+ cell ratios were significantly increased in effective patients after C+C treatment, but didn't increase in progressive disease (PD) patients. Higher percentage of Total T, CD4+T, and higher CD4+/CD8+ cell ratios post-treatment were associated with longer OS. CONCLUSIONS: Camrelizumab combining chemotherapy significantly prolonged the mPFS and mOS of advanced BTC patients. Immunotherapy may improve the immune status of advanced patients, and immunotherapy efficacy might be predicted based on the peripheral blood lymphocyte subsets.

Inflammatory markers related to survival in breast cancer patients: Peru.

INTRODUCTION: Breast cancer is a disease with high global prevalence. Clinical inflammatory biomarkers have been proposed as prognostic indicators in oncology. This research aims to determine the relationship between inflammatory markers and overall survival in breast cancer patients from four representative hospitals in Lima, Peru. METHODS: This is a multicentric, analytical, longitudinal retrospective cohort study with survival analysis in female patients with breast cancer, from 2015 to 2020, who had received at least one complete treatment regimen. The dependent variable was overall survival, and the independent variables were inflammatory markers neutrophil lymphocyte ratio, platelet lymphocyte ratio (PLR), albumin, and red cell distribution width; intervening variables included age, clinical stage, molecular subtype, and other known prognostic factors. The Kaplan-Meier method was applied to generate survival curves with the Log-Rank test, and finally, Cox regression, to find crude and adjusted hazard ratios (HR). RESULTS: Of 705 evaluated patients, 618 were analyzed. The mean age was 56.6 ± 12.3 years, 18.0% of patients were pure HER2 positive, 39.3% luminal A, 29.9% luminal B, 11.0% triple-negative, and 81.4% showed overweight and obesity. The average overall survival was 51.1 months. In the multivariate analysis, factors significantly related to lower overall survival were PLR > 150 (adjusted HR: 2.33; 95% confidence interval (CI): 1.22, 4.44) and stage III (adjusted HR: 4.15; 95% CI: 1.35, 12.83). CONCLUSIONS: The Elevated Platelet-Lymphocyte Index and advanced clinical stage were associated with lower overall survival in breast cancer patients. Furthermore, PLR >150 proved to be an independent prognostic factor for mortality.

Association of neutrophil-to-lymphocyte ratio with age and 180-day mortality after emergency surgery.

BACKGROUND: To examine the relationship between neutrophil-to-lymphocyte ratio (NLR), age, and mortality rates after emergency surgery. METHODS: In this observational study, a total of 851 patients undergoing emergency surgery between January 2022 and January 2023 were retrospective examined. Using 30 and 180 days mortality data, NLR differences and receiver operating characteristic (ROC) curves were analyzed using a 65-year threshold. A multiple logistic regression model was constructed incorporating age and NLR. Finally, Kaplan-Meier curves were constructed for mortality. RESULTS: Among 851 patients, the 30 and 180 days mortality rates were 5.2% and 10.8%, respectively. Median NLR in 30 days was 5.6 (3.1 to 9.6) in survivors and 8.7 (4.6 to 13.4) in deceased patients (p < 0.0001); in 180 days, it was 5.5 (3.1 to 9.8) and 8.8 (4.8 to 14.5), respectively (p < 0.0001). In the 30- and 180-days mortality analyses, median NLRs were 5.1 (2.9 to 8.9) and 4.9 (2.9 to 8.8) in survivors and 10.6 (6.9 to 16.6) and 9.3 (5.4 to 14.9) in deceased patients aged < 65 years, respectively. The ROC AUC in patients younger than 65 years was higher for 30 days (AUC 0.75; 95% CI 0.72 to 0.87) and 180 days (AUC 0.73; 95% CI 0.64 to 0.81). Multivariate logistic regression revealed that the NLR (odds ratio, 1.03 [95% CI 1.005 to 1.053; p = 0.0133) and age (odds ratio, 1.05 [95% CI 1.034 to 1.064; p < 0.0001) significantly contributed to the model. Survival analysis revealed differences in the 180 days mortality (p = 0.0006). CONCLUSION: We observed differences in preoperative NLR between patients who survived and those who died after emergency surgery. Age impacts the use of NLR as a mortality risk factor. TRIAL REGISTRATION: NCT06549101, retrospectively registered.

Clinical predictive factors of the efficacy of immune checkpoint inhibitors and kinase inhibitors in advanced hepatocellular cancer.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly aggressive tumor associated with significant morbidity and mortality rates. Combination therapy with immune checkpoint inhibitors (ICIs) and kinase inhibitors has emerged as a promising strategy for liver cancer treatment in recent years. However, the clinical factors predicting the outcomes of combination therapy in patients with advanced liver cancer remain uncertain. Therefore, this study investigated the relationships between clinical predictors and the efficacy of ICI plus kinase inhibitor therapy to personalize treatment plans. METHODS: We retrospectively enrolled 98 patients who received combination treatment with ICIs and kinase inhibitors for advanced HCC. Based on blood lipid levels and other clinical factors prior to treatment, we investigated potential biomarkers that could predict treatment responses in this patient population. RESULTS: Mean progression-free survival (PFS) and overall survival (OS) in this cohort were 10.1 and 17.2 months, respectively. Via multivariate analysis, the absence of extrahepatic metastasis, the absence of portal vein thrombosis (PVT), neutrophil-to-lymphocyte ratio (NLR) < 3.225, platelet-to-lymphocyte ratio (PLR) < 140.75, and prognostic nutritional index (PNI) ≥ 37.25 were identified as independent predictors of improved PFS. Factors associated with better OS included PLR < 140.75 and total cholesterol (TC) < 3.46 mmol/L. Univariate analysis identified significant associations of Eastern Cooperative Oncology Group performance status (ECOG PS), hepatitis B virus (HBV) DNA levels, Child-Pugh classification, alpha-fetoprotein (AFP), TC, and the receipt of regorafenib with PFS. Additionally, ECOG PS, Child-Pugh classification, AFP, PVT, NLR, PNI, and the receipt of regorafenib were significantly associated with OS. CONCLUSIONS: PLR and TC were potential clinical predictive factors for survival outcomes in patients with advanced HCC who received ICI/kinase inhibitor combination therapy. It is important to know the clinical characteristics of patients prior to treatment initiation to optimize outcomes.

Neutrophil-to-Lymphocyte Ratio and Cytokine Profiling as Predictors of Disease Severity and Survival in Unvaccinated COVID-19 Patients.

BACKGROUND: During the COVID-19 pandemic, identifying reliable biomarkers for predicting disease severity and patient outcomes in unvaccinated individuals is essential. This study evaluates the efficacy of key hematological markers, including leukocyte and neutrophil counts, Neutrophil-to-Lymphocyte Ratio (NLR), and cytokine profiles (IL-6, INF-γ, TNF-α, IL-17A, CCL2, and CXCL10) for predicting the necessity for mechanical ventilation and assessing survival probabilities. METHODS: We conducted an in-depth analysis on a cohort of COVID-19 patients, emphasizing the relationship between NLR, cytokine profiles, and clinical outcomes, utilizing routine leukocyte counting and cytokine quantification by flow cytometry. RESULTS: Elevated leukocyte and neutrophil counts, increased NLR, and significant cytokine elevations such as IL-6 and IL-10 were strongly associated with the need for mechanical ventilation, reflecting a pronounced systemic inflammatory response indicative of severe disease outcomes. CONCLUSION: Integrating hematological markers, particularly NLR and cytokine profiles, is crucial in predicting mechanical ventilation needs and survival in non-vaccinated COVID-19 patients. Our findings provide critical insights into the pathophysiology of COVID-19, supporting the development of more targeted clinical interventions and potentially informing future strategies for managing infectious disease outbreaks.

[Neutrophil-lymphocyte ratio as predictor of mortality in patients with necrotizing fasciitis]. / Índice neutrófilo-linfocito como predictor de mortalidad en pacientes con fascitis necrotizante.

Background: Necrotizing fasciitis (NF) can affect any soft tissue and skin of the body. Its progression is rapid and it is associated with a high mortality rate. Therefore, the search for easily accessible and low-cost biomarkers that could predict the prognosis of patients with NF is necessary. Objective: To evaluate the role of neutrophil-lymphocyte ratio (NLR) as a predictor of mortality in patients with NF. Material and methods: Observational, cross-sectional, retrospective and analytical study of patients admitted between April and October 2020 in a tertiary-care hospital. The statistical tests used for the comparison of variables between the study groups were chi-square, Fisher's exact, Student's t and Mann-Whitney U. A receiver operating characteristic (ROC) curve was performed to determine the accuracy of NLR in predicting mortality in patients with NF. Results: A total of 25 patients were included and stratified into non-survivors and survivors. The non-survivor group had an elevated NLR value compared to survivors (15.57 [13.75] vs. 7.91 [4.13]; p = 0.065). The NLR had an area under the curve (AUC) of 0.729 (95% confidence interval [95% CI] 0.516-0.886; p = 0.044), sensitivity of 77.78% (40-97.2), and specificity of 75% (47.6-92.7). The optimal cut-off point obtained for NLR was > 9.21. Conclusions: An NLR value > 9.21 could be a predictor of mortality in patients with NF.

Introducción: la fascitis necrotizante (FN) puede afectar cualquier tejido blando y piel del cuerpo. Su progresión es rápida y está relacionada con un índice de mortalidad alto. Por lo tanto, la búsqueda de biomarcadores de fácil acceso y bajo costo que puedan predecir el pronóstico de los pacientes con FN es necesaria. Objetivo: evaluar el papel del índice neutrofilo-linfocito (INL) como un predictor de mortalidad en los pacientes con FN. Material y métodos: estudio observacional, transversal, retrospectivo y analítico de pacientes admitidos entre abril y octubre del 2020 en un hospital de tercer nivel. Las pruebas estadísticas utilizadas para la comparación de las variables entre los grupos de estudio fueron chi cuadrado, exacta de Fisher, t de Student y U de Mann-Whitney. Una curva característica operativa del receptor (ROC) fue realizada para determinar la precisión del INL en la predicción de mortalidad en pacientes con FN. Resultados: un total de 25 pacientes fueron incluidos y estratificados en no sobrevivientes y sobrevivientes. El grupo no sobreviviente tuvo un valor elevado del INL en comparación con los sobrevivientes (15.57 [13.75] frente a 7.91 [4.13]; p = 0.065). El INL tuvo un área bajo la curva (AUC) de 0.729 (intervalo de confianza del 95% [IC 95%] 0.516-0.886; p = 0.044), sensibilidad de 77.78% (40-97.2) y especificidad de 75% (47.6-92.7). El punto de corte óptimo obtenido para el INL fue > 9.21. Conclusiones: un valor de INL > 9.21 podría ser un predictor de mortalidad en los pacientes con FN.

Case Report: C3 deficiency in two siblings.

The complement system, a vital component of innate immunity, consists of various proteins and pathways crucial for the recognition and elimination of pathogens. In addition, it plays a major role in the initiation of adaptive response through the opsonization of antigens, contributing to B-cell activation and memory maintenance. Deficiencies in complement proteins, particularly C3, can lead to severe and recurrent infections as well as immune complex disorders. Here, we present a case report of two siblings with total C3 deficiency resulting from compound heterozygous mutations in C3 (NM_000064.4): c.305dup; [p.Asn103GlnfsTer66] and c.1269 + 5G>T, previously unreported in C3-related diseases. Both, the index case and her sister, presented a history of recurrent infections since early childhood and one of them developed hemolytic uremic syndrome (HUS). Immunological evaluation revealed absent plasma C3 levels, decreased memory B cells, hypogammaglobulinemia, and impaired response to polysaccharide antigens. The siblings showed partial responses to antimicrobial prophylaxis and vaccination, requiring intravenous immunoglobulin replacement therapy, resulting in clinical improvement. Genetic analysis identified additional risk polymorphisms associated with atypical HUS. This case highlights the importance of comprehensive genetic and immunological evaluations in complement deficiencies, along with the potential role of immunoglobulin replacement therapy in managing associated antibody defects.

Weak association between urea-creatinine ratio and c-reactive protein with nutritional risk in hospitalized patients with COVID-19: A cross-sectional study.

BACKGROUND: COVID-19 is a systemic infection with a significant impact on nutrition risk and the hematopoietic system. The neutrophil-lymphocyte ratio (NLR) may have prognostic value in determining severe cases of COVID-19 and the urea-creatinine ratio (UCR) is currently being studied as a potential biomarker of catabolism associated with critical illness. The aim was to assess the association between the NLR, UCR and C-reactive protein (CRP) with nutritional risk in hospitalized patients with COVID-19. METHODS: This is a retrospective cross-sectional study that assessed 589 hospitalized patients with COVID-19, 18 years of age or older, of both sexes. Nutritional risk was assessed by Nutritional Risk Screening (NRS, 2002) and NLR by neutrophils divided by lymphocyte count. The UCR was calculated by the ratio between urea and creatinine and quantified by the calorimetric biochemical method and CRP by the immunoturbidimetric method. Differences between groups were applied by the Mann-Whitney U test and the automated binary regression test. RESULTS: Of the 589 patients, 87.4% were at nutritional risk. When evaluating patients admitted to the ICU, 91.9% were at nutritional risk. Patients with NRS ≥3 are older, with lower body mass and BMI, higher NLR and UCR and lower CRP values. However, 73% of patients admitted to the ward were at nutritional risk, and only age differed between groups, being higher in patients with NRS ≥3. Logistic regression showed a weak association between nutritional risk in NRS and UCR (Model 1) (OR = 0.96, 95%CI: 0.94-0.99, p = 0.003) and NRS with CRP (Model 1) (OR = 1.01, 95%CI: 1.00-1.02, p < 0.001) in patients in the ICU. On the other hand, the logistic regression in ward patients found association only for CRP in both models (Model 1, OR = 1.01, 95%CI: 1.00-1.01, p = 0.041) and (Model 2, OR = 1.01, 95%CI: 1.00-1.01, p = 0.031). CONCLUSION: We found a weak association between nutritional risk and UCR and CRP levels in patients admitted to the ICU, while in the ward patients the nutritional risk also had weak association with CRP.

Walking one hour per day and the derived neutrophil-to-lymphocyte ratio are associated with outcome in palliative second-line immunotherapy for patients with recurrent and/or metastatic squamous cell carcinoma of head and neck.

OBJECTIVES: To determine whether routinary walking activity and the derived neutrophil-to-lymphocyte ratio are associated with outcomes in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. METHODS: This multicenter retrospective cohort study included 64 patients diagnosed with recurrent and/or metastatic squamous cell carcinoma of head and neck and treated with immunotherapy (Programmed Death-1 and Programmed Death-ligand-1 proteins inhibitors) at two tertiary centers. We compared a group that performed uninterrupted physical activity for 1 h per day and controls who performed no activity. The derived neutrophil-to-lymphocyte ratio was calculated as follows: [neutrophils / (leukocytes - neutrophils)]. Progression-free survival and overall survival were evaluated. RESULTS: We included 28 (44%) and 36 (56%) patients in the activity and non-activity groups, respectively. Patient characteristics, treatment details, and tumor Programmed Death-ligand-1 expression were not associated with either progression-free survival or overall survival. Physical activity was an independent beneficial factor for progression-free survival (p < 0.001) and overall survival (p < 0.001). By contrast, a derived neutrophil-to-lymphocyte ratio <3.5 was an independent beneficial factor for overall survival (p = 0.013), but not for progression-free survival (p = 0.328). CONCLUSIONS: Walking one hour per day and having a high proportion of lymphocytes to neutrophiles (expressed as a low derived neutrophil-to-lymphocyte ratio) independently predict a better prognosis in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck treated with immunotherapy. LEVEL OF EVIDENCE: III.

Evolución de los parámetros hematológicos y óbito en internados con COVID-19 en un hospital de Paraguay, 2021

Introducción: Los parámetros hematológicos proporcionan al equipo médico marcadores pronósticos útiles en la evolución clínica de la enfermedad de COVID-19. El objetivo fue analizar la relación entre la evolución desfavorable de los valores hematológicos y el óbito de los pacientes internados con COVID-19. Metodologia: El estudio es observacional, correlacional y longitudinal. Se realizó la revisión de fichas clínicas de los pacientes mayores a 18 años internados entre enero y marzo del 2021. Se registró en una planilla Excel el resultado de los parámetros hematológicos al ingreso, a las 48 horas, a los 8 días y al egreso. Los datos fueron analizados con Epi Info 7.1 (CDC, Atlanta) según estadística descriptiva. Resultados: De 144 pacientes, se observaron 68 (47,2%) muertes, con predominio del sexo masculino (63,2%) y, mayores a 60 años (47,1%). Los factores asociados a mortalidad fueron la hipertensión (52,9% vs 31,6%; p=0,009), la diabetes (50% vs 26,3%; p=0,003) y, la obesidad (41,2% vs 25%; p=0,039). Los parámetros hematológicos desfavorables asociados a la mortalidad se presentaron a partir de los 8 días de internación con leucocitosis (64,1% vs 33,3%; p=0,003), linfopenia (96,8% vs 79%; p=0,008), neutrofilia (98,5% vs 87,7%; p=0,029) y, un elevado índice neutrófilo/linfocito (INL) (96,9% vs 75,4%; p=0,001). Discusión: Los parámetros hematológicos que se asociaron con la mortalidad fueron leucocitosis con neutrofilia, linfopenia e INL elevado. Estos parámetros podrían tener valor pronóstico en el seguimiento para contribuir en el manejo de estos pacientes.

Introduction: Hematological parameters provide the medical team with useful prognostic markers in the clinical evolution of COVID-19 disease. The objective was to analyze the relationship between the unfavorable evolution of hematological values and the death of patients hospitalized with COVID-19. Methodology: The study is observational, correlational, and longitudinal. A review of the clinical records of patients over 18 years of age hospitalized between January and March 2021 was carried out. The results of the hematological parameters at admission, at 48 hours, at 8 days and at discharge were recorded in an Excel spreadsheet. The data were analyzed with Epi Info 7.1 (CDC, Atlanta) according to descriptive statistics. Results: Of 144 patients, 68 (47.2%) deaths were observed, with a predominance of males (63.2%) and those over 60 years of age (47.1%). The factors associated with mortality were hypertension (52.9% vs 31.6%; p=0.009), diabetes (50% vs 26.3%; p=0.003) and obesity (41.2% vs 25 %; p=0.039). The unfavorable hematological parameters associated with mortality occurred after 8 days of hospitalization with leukocytosis (64.1% vs 33.3%; p=0.003), lymphopenia (96.8% vs 79%; p=0.008), neutrophilia (98.5% vs 87.7%; p=0.029) and a high neutrophil/lymphocyte ratio (NLR) (96.9% vs 75.4%; p=0.001). Discussion: The hematological parameters that were associated with mortality were leukocytosis with neutrophilia, lymphopenia, and elevated NLR. These parameters could have prognostic value in follow-up to contribute to the management of these patients.

Lower proportion of intra-thyroidal B lymphocytes CD20+ associated to methimazole and lack of influence of iodide on lymphocyte subpopulations in Graves' disease.

Graves' disease (GD), an autoimmune thyroid disease, is one of the main autoimmune diseases in the general population. It is known that the pathophysiology of this disease may be related to immunological mechanisms dysregulation. These mechanisms can be influenced by GD therapies, such as iodide or antithyroid drugs (ATD). OBJECTIVE: Verify relation between clinical, biochemical and treatment modalities used prior to surgery and histopathological characteristics observed in total thyroidectomy products from patients previously diagnosed with Graves' disease. Furthermore, these data were related to composition of lymphocytic infiltrate in terms of proportions of lymphocytes CD4+, CD8+, CD25+ and CD20+. We aim to contribute to the understanding of the evolution pattern of GD, whose pathophysiology is not yet completely understood. METHODS: Cross-sectional study assessing thyroidectomy products for the presence of lymphocytic infiltrate, as well as the proportion and intensity of CD4+, CD8+, CD25+ and CD20+ markers. We selected 50 patients who underwent total or partial thyroidectomy in a tertiary service between 1996 and 2013 due to GD with histopathological confirmation. The control group (non-autoimmune disease group) consisted of 12 patients with histopathological data compatible with normal perilesional thyroid parenchyma. The intensity of lymphocytic infiltrate and immunohistochemical expression of the markers CD4+ (helper T lymphocytes), CD8+ (cytotoxic T lymphocytes), CD25+ (regulatory T lymphocytes) and CD20+ (B lymphocytes) were retrospectively evaluated and relationship with ultrasound, laboratory and clinical data was assessed. RESULTS: No differences were found in intensity, presence of lymphoid follicles, and expression of CD4+/CD8+/CD25+ in patients with GD who did or did not use ATD or iodide. In the group that did not use ATD, a higher proportion of CD20+ expression was found. The GD group was associated with hyperplastic epithelium and the control group was associated with simple epithelium. There was no difference in ultrasound thyroid volume between the groups. In GD patients with mild lymphocytic infiltrate, higher free thyroxin (FT4) levels were observed than those in patients with no infiltrate or moderate infiltrate. CONCLUSION: We found a lower proportion of intrathyroidal CD20+ B lymphocytes in patients under use of methimazole. However, no difference was observed in intrathyroidal lymphocyte subpopulations related to the short-term use of iodide. The understanding of thyroid autoimmunity, as well as identifying points of pharmacological modulation, are very important for advancement and improvement in treatments for these diseases.

Immune response and cytokine profiles in post-laminectomy pain syndrome: comparative analysis after treatment with intrathecal opioids, oral opioids, and non-opioid therapies.

INTRODUCTION: This study explores the interaction between cytokines, cell-mediated immunity (T cells, B cells, and NK cells), and prolonged morphine administration in chronic neuropathic pain patients without cancer-related issues. Despite evidence of opioid immunomodulation, few studies have compared these interactions. METHODS: In a cross-sectional and comparative study, 50 patients with chronic low back radicular pain ("Failed Back Surgery Syndrome") were categorized into intrathecal morphine infusion (IT group, n = 18), oral morphine (PO group, n = 17), and non-opioid treatment (NO group, n = 15). Various parameters, including plasma and cerebrospinal fluid (CSF) cytokine concentrations, lymphocyte immunophenotyping, opioid escalation indices, cumulative morphine dose, and treatment duration, were assessed. RESULTS: CSF IL-8 and IL-1ß concentrations exceeded plasma levels in all patients. No differences in T, B, and NK lymphocyte numbers were observed between morphine-treated and non-treated patients. Higher plasma IL-5 and GM-CSF concentrations were noted in IT and PO groups compared to NO. CSF IFNγ concentrations were higher in PO and NO than IT. Positive correlations included CD4 concentrations with opioid escalation indices, and negative correlations involved NK cell concentrations, CSF TNFα concentrations, and opioid escalation indices. Positive correlations were identified between certain cytokines and pain intensity in IT patients, and between NK cells and cumulative morphine dose. Negative correlations were observed between CSF IL-5 concentrations and pain intensity in IT and PO, and between opioid escalation indices and CSF cytokine concentrations in PO and IT. CONCLUSION: Associations between cytokines, cellular immunity, and prolonged morphine treatment, administered orally and intrathecally were identified.

Current status and perspectives of clinical trials for tumor-infiltrating lymphocyte therapy.

Immunotherapies, mainly immune checkpoint inhibitors (ICIs), have revolutionized cancer treatment strategies over the past decade, but their limitations have limited clinical applications. Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive cell therapy (ACT), which collects infiltrating lymphocytes at the tumor site and expands them in vitro to obtain TIL final products cloned by various T-cell receptors, subsequently reinfused TIL into the patient, which is effective for the treatment of solid tumors. The approval of Lifileucel for commercialization marks the success of TIL therapy. This review summarizes the current status of clinical trials of TIL treatment. In addition, it is suggested that the current research trend of TIL should focus on improving the survival time of TIL in vivo, reducing drug toxicity, and searching for prognostic markers. Finally, it is expected that TIL therapy can be applied to a more wide range of clinical treatments.

Association of albumin, neutrophil-lymphocyte ratio and lymphocytes with clinical stage in cervical cancer patients.

OBJECTIVE: To determinate the association between of albumin, neutrophil-lymphocyte ratio and lymphocytes (NLR) with clinical stage in cervical cancers. METHODS: Design a retrospective cross-sectional study of consecutive subjects diagnosed with cervical cancer for the first time. The Bethesda system was used for histological diagnosis and the subjects were stratified with the FIGO system, considering stages IA to IIB as localized; while, IIIA and IVB as advanced stages. Albumin, NLR and lymphocytes were evaluated as inflammatory biomarkers and the cut-off points generated by the ROC curves were albumin < 3 mg/dL, NLR ≥ 2.0 and lymphocytes < 1.2 103/ul. The association was calculated by Odds Ratios (OR) with 95% confidence intervals. RESULTS: A total of 152 patients were analyzed, with mean age of 49.3 ± 14.0 years. Epidermoid cancer was the most frequent in 70.6% and 51.3% were classified as advanced clinical stages. A bivariate analysis showed significant relationships between advanced clinical stages and albumin < 3 mg/dL with OR 5.72 (CI95% 2.62-12.4; p < 0.001); for NLR ≥ 2.0 an OR 2.53 (CI95% 1.34-4.89; p = 0.005) and for lymphocytes < 1.2 103/ul of OR 3.39 (CI95% = 1.73-6.65; p < 0.001). CONCLUSIONS: Albumin levels < 3 mg/dL, NLR ≥ 2.0 and lymphocytes < 1.2 103/ul, were associated with advanced stages in subjects with cervical cancer.

The potential value of dual-energy CT radiomics in evaluating CD8+, CD163+ and αSMA+ cells in the tumor microenvironment of clear cell renal cell carcinoma.

PURPOSE: This study aims to develop radiomics models and a nomogram based on machine learning techniques, preoperative dual-energy computed tomography (DECT) images, clinical and pathological characteristics, to explore the tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC). METHODS: We retrospectively recruited of 87 patients diagnosed with ccRCC through pathological confirmation from Center I (training set, n = 69; validation set, n = 18), and collected their DECT images and clinical information. Feature selection was conducted using variance threshold, SelectKBest, and the least absolute shrinkage and selection operator (LASSO). Radiomics models were then established using 14 classifiers to predict TME cells. Subsequently, we selected the most predictive radiomics features to calculate the radiomics score (Radscore). A combined model was constructed through multivariate logistic regression analysis combining the Radscore and relevant clinical characteristics, and presented in the form of a nomogram. Additionally, 17 patients were recruited from Center II as an external validation cohort for the nomogram. The performance of the models was assessed using methods such as the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: The validation set AUC values for the radiomics models assessing CD8+, CD163+, and αSMA+ cells were 0.875, 0.889, and 0.864, respectively. Additionally, the external validation cohort AUC value for the nomogram reaches 0.849 and shows good calibration. CONCLUSION: Radiomics models could allow for non-invasive assessment of TME cells from DECT images in ccRCC patients, promising to enhance our understanding and management of the tumor.

Lymphocyte Levels and Morbidity and Mortality in Cardiovascular Surgery With Cardiopulmonary Bypass.

INTRODUCTION: A year ago, in a sample of 113 patients, our research group found that a high number of lymphocytes in the immediate postoperative period was correlated to a poor prognosis in cardiovascular surgeries. This study is an expansion of the initial study in order to confirm this finding. METHODS: We analyzed the data of 338 consecutive patients submitted to cardiovascular surgeries with cardiopulmonary bypass performed at Hospital Universitário Ciências Médicas (Belo Horizonte/Brazil) from 2015 to 2017. We analyzed 39 variables with the outcomes death, hospital stay, and intensive care unit stay. RESULTS: The value of lymphocytes in the immediate postoperative period > 2175.0/mm³ was an indicator of poor prognosis in this sample (P<0.001). The variables female sex, age, high level of European System for Cardiac Operative Risk Evaluation II, increased stay in the intensive care unit and in the ward, elevation of creatinine in the preoperative period and at intensive care unit discharge, elevation of the percentage of immediate postoperative period segmented neutrophils, high immediate postoperative period neutrophil/lymphocyte ratio, fasting hyperglycemia, preoperative critical condition, reintubation, mild or transient acute renal failure, surgical infection, cardiopulmonary bypass, and aortic cross-clamping and mechanical ventilation durations also had an impact on the mortality outcome. CONCLUSION: The value of lymphocytes in the immediate postoperative period > 2175.0/mm3 was an indicator of poor prognosis in cardiovascular surgery with cardiopulmonary bypass.

Neutrophil-to-lymphocyte ratio may predict complications and patency in bile duct injury repair.

BACKGROUND: Bile duct injury (BDI) repair surgery is usually associated with morbidity/mortality. The neutrophil-to-lymphocyte ratio (NLR) easily assesses a patient's inflammatory status. The study aims to determine the possible relationship between preoperative NLR (pNLR) with postoperative outcomes in BDI repair surgery. METHODS: Approved Ethics/Research Committee retrospective study, in patients who had a Bismuth-Strasberg type E BDI repair (2008-2023). Data registered was: morbidity, mortality, and long-term outcomes (primary patency and loss of primary patency) (Kaplan-Meier). Group comparison (U Mann-Whitney), receiver operator characteristic (ROC): area under curve [AUC]; cut-off value, and Youden index [J], and logistic regression analysis were used for pNLR evaluation. RESULTS: Seventy-three patients were studied. Mean age was 44.4 years. E2 was the commonest BDI (38.4%). Perioperative morbidity/mortality was 31.5% and 1.4%. Primary patency was 95.9%. 8.2% have lost primary patency (3-year actuarial patency: 85.3%). Median pNLR was higher in patients who had any complication (4.84 vs. 2.89 p = 0.015), biliary complications (5.29 vs. 2.86 p = 0.01), and patients with loss of primary patency (5.22 vs. 3.1 p = 0.08). AUC's, cut-off values and (J) were: any complication (0.678, pNLR = 4.3, J = 0.38, p = 0.007), serious complication (0.667, pNLR = 4.3, J = 0.34, p = 0.04), biliary complications (0.712, pNLR = 3.64, J = 0.46, p = 0.001), and loss of primary patency (0.716, pNLR = 3.24, J = 0.52, p = 0.008). Logistic regression was significant in any complication (Exp [B]: 0.1, p = 0.002), serious complications (Exp [B]: 0.2, p = 0.03), and biliary complications (Exp [B]: 8.1, p = 0.003). CONCLUSIONS: pNLR is associated with complications in BDI repair with moderate to acceptable predictive capacity. pNLR could potentially predict patency of a BDI repair.

Association between CD4 lymphocyte count and the incidence of comorbidities in Human immunodeficiency virus positive patients with virological suppression after antiretroviral treatment.

BACKGROUND: The incidence of comorbidities is higher in HIV-positive patients than in the general population due to factors, such as HIV-related chronic inflammation. There is no consensus on whether a low CD4 lymphocyte count after virological suppression at long-term follow-up increases the risk of comorbidities. This study evaluates the association between CD4 lymphocyte count and the incidence of comorbidities during the first 5 years of virological suppression after highly active antiretroviral treatment. METHODS: We conducted a cohort study of HIV-positive adults who achieved virological suppression in an HIV program between 2002 and 2016 in Colombia. A generalized equation estimation model was used to estimate the association between CD4 lymphocyte count and the incidence of comorbidities. RESULTS: A follow-up period of at least 1 year was completed in 921 HIV-positive patients with virological suppression. We found 71 comorbidities during a maximum of 5 years of follow-up; 41 (59%) were AIDS-defining comorbidities and 19 (46%) of them occurred during the first semester. Thirty cases of non-AIDS- defining comorbidities were diagnosed.We did not find any association between CD4 lymphocyte count and the incidence of comorbidities (OR 0.92, CI 95% 0.45 -1.91 for CD4 201-499 cells/µL vs CD4 ≤200 cells/µL, and OR 0.55, 95% CI 0.21-1.44 for CD4 ≥500 cells/µL vs CD4 ≤200 cells/µL). CONCLUSION: No association was found between CD4 lymphocyte count and the incidence of AIDS-defining or non-AIDS-defining comorbidities in patients with virological suppression. Further studies are needed to assess the risk of comorbidities in this population to design interventions aimed at improving their prognosis.

Association of neutrophil/lymphocyte and platelet/lymphocyte ratios with inflammation and survival in Mexican patients on chronic hemodialysis.

INTRODUCTION: Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are markers of systemic inflammatory status. The relationship between NLR, PLR, and mortality is controversial among hemodialysis (HD) patients. OBJECTIVE: Evaluate NLR and PLR in the prediction of mortality in chronic HD patients. MATERIALS AND METHODS: We analyzed 130 patients with a follow-up for 66 months. Four groups were established according to NLR-PLR values. Kaplan-Meier curves and Cox proportional hazards analysis were used. RESULTS: NLR-PLR correlated positively with C-reactive protein. Cox regression analysis for overall mortality among the four groups included age (HR 1.027, 95% CI 1.003-1.053) and albumin (HR 0.25, 95% CI 0.073-0.85). For cardiovascular (CV) mortality only pulse pressure differential (PPD) was included (HR 1.033; 95% CI 1.014-1.052). Low NLRs and high PLRs were associated with CV mortality (Log Rank test, p = 0.033). CONCLUSIONS: Low NLRs and high PLRs predict the risk of CV mortality among HD patients.