Icanbelimod (CBP-307), a next-generation Sphingosine-1-phosphate receptor modulator, in healthy men: pharmacokinetics, pharmacodynamics, safety, and tolerability in a randomized trial in Australia.

Background: Icanbelimod (formerly CBP-307) is a next-generation S1PR modulator, targeting S1PR1. In this first-in-human study, icanbelimod was investigated in healthy men in Australia. Methods: Participants were randomized 3:1, double-blind, to icanbelimod or placebo in four single-dose cohorts (0.1 mg, 0.25 mg, 0.5 mg [n=8 per cohort], 2.5 mg [n=4]) or for 28-days once-daily treatment in two cohorts (0.15 mg, 0.25 mg [n=8 per cohort]). Participants in the 0.25-mg cohort received 0.1 mg on Day 1. Treatments were administered orally after fasting; following one-week washout, icanbelimod was administered after breakfast in the 0.5-mg cohort. Results: Icanbelimod exposure increased rapidly and dose-dependently with single and multiple dosing (Tmax 4-7 hours). Lymphocyte counts decreased rapidly after single (-11%, 0.1 mg; -40%, 0.25 mg; -71%, 0.5 mg; -77%, 2.5 mg) and multiple doses (-49%, 0.15 mg; -75%, 0.25 mg), and recovered quickly, 7 days after dosing. After single-dose 0.5 mg, although a high-fat breakfast versus fasting did not affect maximal decrease, lymphocyte counts tended to be lower after breakfast across most timepoints up to 72 hours. Twenty-eight participants (63.6%) experienced mainly mild treatment-emergent adverse events (TEAEs). After single-dose icanbelimod, the most common TEAEs were headache (28.6%, n=6) and dizziness (19.0%, n=4). Three participants experienced transient bradycardia, with one serious, following single-dose 2.5 mg icanbelimod. After multiple-dose icanbelimod, the most common TEAEs were headache (50.0%, n=6) and lymphopenia (41.7%, n=5), and two participants withdrew due to non-serious TEAEs. Up-titration attenuated heart rate reductions. Conclusion: Icanbelimod was well-tolerated up to 0.5 mg and effectively reduced lymphocyte counts. Clinical trial registration: ClinicalTrials.gov, identifier NCT02280434.b.

Association between lymphocyte-to-monocyte ratio and prostate cancer in men: A population-based study.

Using the novel inflammatory biomarker lymphocyte-to-monocyte ratio (LMR), this work aimed to look into any potential connections between LMR and prostate cancer (PCa). A cross-sectional research investigation was conducted on 7706 male participants involved in the National Health and Nutrition Examination Survey from 2001 to 2010. Multivariate logistic regression modeling investigated the relationship between LMR levels and PCa risk. Furthermore, threshold analysis, subgroup analysis, interaction testing, and smoothed curve fitting were carried out. A significant negative correlation was seen between LMR and PCa risk (OR = 0.79, 95% CI: 0.65-0.97, P = .0002), even after controlling for potential confounding factors. A significant nonlinear negative correlation with a threshold effect and a breakpoint of 4.86 was found by smooth curve fitting between LMR and PCa. Subgroup analysis revealed a significant interaction (P for interaction = 0.0448) between the negative correlation between PCa and LMR about hypertension. Moreover, additional stratified smoothed curve fitting demonstrated a statistically significant inverse relationship between PCa risk and LMR. According to our findings, there is a substantial inverse relationship between PCa risk and LMR level. The inflammatory response-related index is quick, easy to use, and offers some clinical references. However, more extensive prospective investigations are required to confirm the involvement of LMR levels in PCa.

A nomogram combining neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) to predict distant metastasis in gastric cancer.

In this study, We aim to explore the association between the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), lymphocyte to monocyte ratio (LMR) and prognostic nutritional index (PNI) and distant metastasis of gastric cancer and develop an efficient nomogram for screening patients with distant metastasis. A total of 1281 inpatients with gastric cancer were enrolled and divided into the training and validation set.Univariate, Lasso regression and Multivariate Logistic Regression Analysis was used to identify the risk factors of distant metastasis. The independent predictive factors were then enrolled in the nomogram model. The nomogram's predictive perform and clinical practicality was evaluated by receiver operating characteristics (ROC) curves, calibration curves and decision curve analysis. Multivariate Logistic Regression Analysis identified D-dimer, CA199, CA125, NLR and PNI as independent predictive factors. The area under the curve of our nomogram based on these factors was 0.838 in the training cohort and 0.811 in the validation cohort. The calibration plots and decision curves demonstrated the nomogram's good predictive performance and clinical practicality in both training and validation cohort. Therefore,our nomogram could be an important tool for clinicians in screening gastric cancer patients with distant metastasis.

The predictors of lymphopenia and its effects on survival in locally advanced esophageal squamous cell carcinoma.

To investigate the impact of the effective radiation dose to immune cells (EDIC) and gross tumor volume (GTV) on lymphopenia and survival in patients with locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2013 and December 2020, 272 LAESCC patients were treated with definitive radiotherapy in two institutions. Based on radiation doses to the lungs, heart, and body region scanned, EDIC was calculated as an equal uniform dose to the total blood considering blood flow and fraction effect. The radiotherapy plan was used to calculate the GTVs. Lymphopenia was graded based on the lowest lymphocyte count during RT. The overall survival (OS), progress-free survival (PFS), and local recurrence-free survival (LRFS) were analyzed statistically. The lowest lymphocyte count was significantly correlated with EDIC (r= -0.389, p < .001) and GTV (r= -0.211, p < .001). Lymphopenia, EDIC, and GTV are risk factors for patients with ESCC. In a Kaplan-Meier analysis with EDIC and GTV as stratification factors, lymphopenia was not associated with OS in the EDIC>12.9 Gy group (p = .294)and EDIC ≤ 12.9 Gy group, and it was also not associated with OS in GTV>68.8 cm3 group (p = .242) and GTV ≤ 68.8 cm3 group(p = .165). GTV and EDIC had an impact on the relationship between lymphopenia and OS in patients with LAESCC undergoing definitive RT. Poorer OS, PFS, and LRFS are correlated with lymphopenia, higher EDIC, and larger GTV.

The prognostic value of the combined neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-platelet ratio (NPR) in sepsis.

Sepsis is a severe disease characterized by high mortality rates. Our aim was to develop an early prognostic indicator of adverse outcomes in sepsis, utilizing easily accessible routine blood tests. A retrospective analysis of sepsis patients from the MIMIC-IV database was conducted. We performed univariate and multivariate regression analyses to identify independent risk factors associated with in-hospital mortality within 28 days. Logistic regression was utilized to combine the neutrophil-to-lymphocyte ratio (NLR) and the neutrophil-to-platelet ratio (NPR) into a composite score, denoted as NLR_NPR. We used ROC curves to compare the prognostic performance of the models and Kaplan-Meier survival curves to assess the 28 day survival rate. Subgroup analysis was performed to evaluate the applicability of NLR_NPR in different subpopulations based on specific characteristics. This study included a total of 1263 sepsis patients, of whom 179 died within 28 days of hospitalization, while 1084 survived beyond 28 days. Multivariate regression analysis identified age, respiratory rate, neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-platelet ratio (NPR), hypertension, and sequential organ failure assessment (SOFA) score as independent risk factors for 28 day mortality in septic patients (P < 0.05). Additionally, in the prediction model based on blood cell-related parameters, the combined NLR_NPR score exhibited the highest predictive value for 28 day mortality (AUC = 0.6666), followed by NLR (AUC = 0.6456) and NPR (AUC = 0.6284). Importantly, the performance of the NLR_NPR score was superior to that of the commonly used SOFA score (AUC = 0.5613). Subgroup analysis showed that NLR_NPR remained an independent risk factor for 28 day in-hospital mortality in the subgroups of age, respiratory rate, and SOFA, although not in the hypertension subgroup. The combined use of NLR and NPR from routine blood tests represents a readily available and reliable predictive marker for 28 day mortality in sepsis patients. These results imply that clinicians should prioritize patients with higher NLR_NPR scores for closer monitoring to reduce mortality rates.

The value of D-dimer and platelet-lymphocyte ratio combined with CT signs for predicting intestinal ischemia in patients with bowel obstruction.

OBJECTIVE: To investigate the diagnostic value of D-dimer, platelet-lymphocyte rate (PLR) and CT signs for intestinal ischemia in patients with bowel obstruction. METHODS: We retrospectively analyzed the clinical and imaging data of 105 patients diagnosed with bowel obstruction, and performed univariate and multivariate analyses to determine the independent risk factors for intestinal ischemia in patients with bowel obstruction. Moreover, the receiver operating characteristic curve (ROC) was plotted to examine the diagnostic value of D-dimer, PLR and CT signs in patients with bowel obstruction. Besides, Kappa tests were used to assess inter-observer agreement. RESULTS: We included 56 men (53%) and 49 women (47%) with mean age of 66.05 ± 16 years. Univariate and multivariate analyses showed that D-dimer, PLR and two significant CT signs (i.e., increased unenhanced bowel-wall attenuation and mesenteric haziness) were independent risk factors for intestinal ischemia in patients with bowel obstruction. ROC analysis showed that the combined use of D-dimer, PLR and the said two CT signs had better performance than single indicators in predicting intestinal ischemia in patients with bowel obstruction. The area under the curve (AUC) of the joint model III was 0.925 [95%CI: 0.876-0.975], with a sensitivity of 79.2% [95CI%: 67.2-91.1] and a specificity of 91.2% [95%CI: 83.7-98.9]. CONCLUSION: The combined use of D-dimer, PLR and CT signs has high diagnostic value for intestinal ischemia in patients with bowel obstruction and will prompt surgical exploration to evaluate intestinal blood flow.

Severity predictors for multisystemic inflammatory syndrome in children after SARS-CoV-2 infection in Vietnam.

Multisystemic inflammatory syndrome in children (MIS-C) might manifest in a broad spectrum of clinical scenarios, ranging from mild features to multi-organ dysfunction and mortality. However, this novel entity has a heterogenicity of data regarding prognostic factors associated with severe outcomes. The present study aimed to identify independent predictors for severity by using multivariate regression models. A total of 391 patients (255 boys and 136 girls) were admitted to Vietnam National Children's Hospital from January 2022 to June 2023. The median age was 85 (range: 2-188) months, and only 12 (3.1%) patients had comorbidities. 161 (41.2%) patients required PICU admission, and the median PICU LOS was 4 (2-7) days. We observed independent factors related to PICU admission, including CRP ≥ 50 (mg/L) (OR 2.52, 95% CI 1.39-4.56, p = 0.002), albumin ≤ 30 (g/L) (OR 3.18, 95% CI 1.63-6.02, p = 0.001), absolute lymphocyte count ≤ 2 (× 109/L) (OR 2.18, 95% CI 1.29-3.71, p = 0.004), ferritin ≥ 300 (ng/mL) (OR 2.35, 95% CI 1.38-4.01), p = 0.002), and LVEF < 60 (%) (OR 2.48, 95% CI 1.28-4.78, p = 0.007). Shock developed in 140 (35.8%) patients, especially for those decreased absolute lymphocyte ≤ 2 (× 109/L) (OR 2.48, 95% CI 1.10-5.61, p = 0.029), albumin ≤ 30 (g/L) (OR 2.53, 95% CI 1.22-5.24, p = 0.013), or LVEF < 60 (%) (OR 2.24, 95% CI 1.12-4.51, p = 0.022). In conclusion, our study emphasized that absolute lymphocyte count, serum albumin, CRP, and LVEF were independent predictors for MIS-C severity. Further well-designed investigations are required to validate their efficacy in predicting MIS-C severe cases, especially compared to other parameters. As MIS-C is a new entity and severe courses may progress aggressively, identifying high-risk patients optimizes clinicians' follow-up and management to improve disease outcomes.

Assessment of COVID-19 risk factors of early and long-term mortality with prediction models of clinical and laboratory variables.

BACKGROUND: Coronavirus disease (COVID-19) may lead to serious complications and increased mortality. The outcomes of patients who survive the early disease period are burdened with persistent long-term symptoms and increased long-term morbidity and mortality. The aim of our study was to determine which baseline parameters may provide the best prediction of early and long-term outcomes. METHODS: The study group comprised 141 patients hospitalized for COVID-19. Demographic data, clinical data and laboratory parameters were collected. The main study endpoints were defined as in-hospital mortality and 1-year mortality. The associations between the baseline data and the study endpoints were evaluated. Prediction models were created. RESULTS: The in-hospital mortality rate was 20.5% (n = 29). Compared with survivors, nonsurvivors were significantly older (p = 0.001) and presented comorbidities, including diabetes (0.027) and atrial fibrillation (p = 0.006). Assessment of baseline laboratory markers and time to early death revealed negative correlations between time to early death and higher IL-6 levels (p = 0.032; Spearman rho - 0.398) and lower lymphocyte counts (p = 0.018; Pearson r -0.438). The one-year mortality rate was 35.5% (n = 50). The 1-year nonsurvivor subgroup was older (p < 0.001) and had more patients with arterial hypertension (p = 0.009), diabetes (p = 0.023), atrial fibrillation (p = 0.046) and active malignancy (p = 0.024) than did the survivor subgroup. The model composed of diabetes and atrial fibrillation and IL-6 with lymphocyte count revealed the highest value for 1-year mortality risk prediction. CONCLUSIONS: Diabetes and atrial fibrillation, as clinical factors, and LDH, IL-6 and lymphocyte count, as laboratory determinants, are the best predictors of COVID-19 mortality risk.

The association between the neutrophil-to-lymphocyte ratio and type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease often accompanied by low-grade inflammation. Recently, the neutrophil-to-lymphocyte ratio (NLR) has garnered researchers' interest as an emerging inflammation biomarker. This study aimed to comprehensively explore the relationship between NLR and T2DM using the National Health and Nutrition Examination Survey (NHANES) database. METHOD: We employed a cross-sectional study design to analyze data from five NHANES cycles from 2007 to 2016, excluding individuals with incomplete data. This study utilized a weighted logistic regression model, subgroup analyses, and restricted cubic spline (RCS) analysis to assess the potential relationship between NLR and T2DM. RESULTS: A total of 9903 participants were eligible for the analysis, of which 1280 were diagnosed with T2DM. The T2DM group exhibited significantly higher NLR levels than the non-T2DM group. After adjusting for potential confounders, elevated NLR levels were associated with an increased risk of developing T2DM, indicated by an odds ratio (OR) of 1.14, 95% CI: (1.05,1.24), P = 0.003. The results of the subgroup analyses revealed a significant interaction effect between NLR and T2DM concerning race and hypertension (P for interaction < 0.05). In contrast, no significant interactions were found for age, sex, education level, body mass index (BMI), smoking status, recreational activities, and alcohol drinker (P for interaction > 0.05). RCS analysis showed a significant non-linear relationship between NLR and T2DM, with an inflection point at 2.27 (all P for non-linearity < 0.05). CONCLUSION: Our study indicates that an elevated neutrophil-to-lymphocyte ratio is associated with a higher risk of T2DM.

Evaluation of immunophenotypic alterations of peripheral blood lymphocytes and their sub-sets in uncomplicated P. Falciparum infection.

BACKGROUND: Malaria is a life-threatening parasitic disease typically transmitted through the bite of an infected Anopheles mosquito. There is ample evidence showing the potential of malaria infection to affect the counts of lymphocyte subpopulations in the peripheral blood, but the extent of alteration might not be consistent in all geographical locations, due to several local factors. Although Ghana is among the malaria-endemic countries, there is currently no available data on the level of alterations that occur in the counts of lymphocyte subpopulations during P. falciparum malaria infection among adults. AIM: The study was to determine the immunophenotypic alterations in the level of peripheral blood lymphocytes and their subsets in adults with uncomplicated P. falciparum malaria infection and apparently healthy participants. METHODS: The study was a cross-sectional comparative study conducted in two municipalities of the Volta region of Ghana. Blood samples were collected from study participants and taken through serology (P. falciparum/Pan Rapid Diagnostic Kits), microscopy (Thick and thin blood films) and Haematological (Flow cytometric and Full blood count) analysis. RESULTS: A total of 414 participants, comprising 214 patients with malaria and 200 apparently healthy individuals (controls) were recruited into this study. Parasite density of the malaria patients ranged from 75/µL to 84,364/µL, with a mean of 3,520/µL. It was also observed that the total lymphocytes slightly decreased in the P. falciparum-infected individuals (Mean ± SD: 2.08 ± 4.93 × 109/L) compared to the control group (Mean ± SD: 2.47 ± 0.80 × 109/L). Again, there was a significant moderate positive correlation between parasite density and haematocrit levels (r = 0.321, p < 0.001). Apart from CD45 + T-cells, more people in the control group had normal values for the lymphocyte subsets measured compared to the malaria patients. CONCLUSIONS: From the results obtained, there was high parasite density among the malaria patients suggestive of high intensity of infection in the case group. The malaria patients again showed considerable haematological alterations in lymphocyte sub-sets and the parasite density appeared to be strongly associated with CD4 + T-cell reduction. Also, the parasite density significantly associated with decreasing haematocrit levels. This indicates that lymphocyte subset enumeration can be used to effectively support malaria diagnosis.

Influence of cryoablation versus operation on circulating lymphocyte subsets in patients with early-stage renal cell carcinoma.

Immune response is known to play an important role in local tumor control especially in renal cell carcinoma (RCC), which is considered highly immunogenic. For localized tumors, operative resection or local ablative procedures such as cryoablation are common therapeutical options. For thermal ablative procedures such as cryoablation, additional immunological anti-tumor effects have been described.The purpose of this prospective study was to determine changes in peripheral blood circulating lymphocytes and various of their subsets in RCC patients treated with cryoablation or surgery in a longitudinal approach using extensive flow cytometry. Additionally, lymphocytes of RCC patients were compared to a healthy control group.We included 25 patients with RCC. Eight underwent cryoablation and 17 underwent surgery. Univariate and multivariable analysis revealed significantly lower values of B cells, CD4 and CD8 T cells, and various of their subsets in the treatment groups versus the healthy control group. Comparing the two different therapeutical approaches, a significant decline of various lymphocyte subsets with a consecutive normalization after three months was seen for the surgery group, whereas cryoablation led to increased values of CD69 + CD4 + and CD69 + CD8 + cell counts as well as memory CD8 + cells after three months.Treatment-naïve RCC patients showed lower peripheral blood lymphocyte counts compared to healthy controls. The post-treatment course revealed different developments of lymphocytes in the surgery versus cryoablation group, and only cryoablation seems to induce a sustained immunological response after three months.

PD-L1 and CD8+ T cell evaluation in breast cancers and their correlation with clinicopathological parameters.

OBJECTIVE: To determine the immunohistochemical expression of Programmed cell Death Ligand 1 and intratumoural cluster of differentiation-8-positive T lymphocyte count in primary breast cancer cases, and to ascertain their association with different clinicopathological parameters. Methods: The cross-sectional study was conducted at the Pakistan Navy Station Shifa Hospital, Karachi, from January 2020 to December 2021, and comprised patients of breast cancer regardless of age. Representative tissue blocks, both prospective and from the 2019 institutional archives, were exposed to immunohistochemical staining with Programmed cell Death Ligand 1 and intratumoural cluster of differentiation-8-positive T lymphocyte antibodies. Pathological and clinical records were used for assessing clinicopathological parameters. Data was analysed using SPSS 23. RESULTS: Of the 70 women with mean age 52.04±12.54 years, 30(42.9%) expressed high Programmed cell Death Ligand 1 positivity, and 55(78.6%) revealed low intratumoural cluster of differentiation-8-positive T lymphocyte count, while 23 (32.9%), had both Programmed cell Death Ligand 1 high positivity and low intratumoural cluster of differentiation-8-positive T lymphocyte count. The association between Programmed cell Death Ligand 1 and intratumoural cluster of differentiation- 8-positive T lymphocytes was not significant (p=0.813). A strong significant association was observed between Programmed cell Death Ligand 1 expression and progesterone receptor negative status (p=0.008). No significant association was observed with any other clinicopathological parameter. CONCLUSIONS: Programmed cell Death Ligand 1 high positivity and low intratumoural cluster of differentiation-8-positive T lymphocyte count were together observed in one-third of the breast cancer cases. A strong significant association existed between Programmed cell Death Ligand 1 high positivity and progesterone receptor negative status.

Efficacy of sarilumab and dexamethasone co-administration for lowering multiple blood biomarkers in the treatment of cytokine release syndrome in hospitalized COVID-19 patients.

The current study was planned to explore the potential synergistic role of the co-administration of sarilumab and dexamethasone in reducing blood biomarkers associated with cytokine release syndrome in hospitalised patients of coronavirus disease-2019. The sample comprised 22 patients hospitalised with severe and critical severity levels and who were treated with sarilumab and dexamethasone. Positive responses were seen in blood biomarkers, including decreased interleukin-6 alpha levels and improved oxygen saturation. Tumour necrosis factor, Ddimer, C-reactive protein, ferritin and lymphocyte count also showed positive responses in patients who survived than those who died. Lactate dehydrogenase levels fluctuated with improvement among the survivors, but had limited effectiveness in those who died. The findings suggested promising avenues for future treatment strategies in patients with severe coronavirus disease-2019 and cytokine release syndrome.

Absolute Lymphocyte Count: a Predictor of Positive Serum PCR for Trypanosoma cruzi in Patients with Chagas Disease Undergoing Heart Transplantation. / Contagem Absoluta de Linfócitos: um Preditor de PCR Sérica Positiva para o Trypanosoma cruzi em Pacientes com Chagas Submetidos ao Transplante Cardíaco.

BACKGROUND: It is unknown whether lymphopenia is a risk factor for the reactivation of Chagas disease in heart transplantation (HTx), as recently described in the reactivation of cytomegalovirus in transplant patients. OBJECTIVE: To evaluate whether lymphopenia in the perioperative period of heart transplantation is related to early Trypanosoma cruzi parasitemia. METHODS: This observational, retrospective study analyzed a sample from January 2014 to January 2023). Parasitemia was evaluated in the first 3 months after HTx using serum polymerase chain reaction (PCR) and compared with the total lymphocyte count in the perioperative period of HTx using receiver operating characteristic curves. Baseline characteristics were compared with PCR for Chagas using independent Cox proportional hazards models. A significance level of 5% was adopted. RESULTS: The sample (n = 35) had a mean age of 52.5 ± 8.1 years, and 22 patients (62.8%) had positive PCR for Chagas. The mean lowest lymphocyte values in the first 14 days after HTx were 398 ± 189 and 755 ± 303 cells/mm3 in patients with and without parasitemia, respectively, within 3 months after HTx (area under the curve = 0.857; 95% confidence interval: 0.996 to 0.718, sensitivity and specificity of 83.3% and 86.4%). A cutoff value of less than 550 lymphocytes/mm3 was determined as a risk factor for the presence of parasitemia. Patients with lymphocytes < 550 units/mm3 in the first 14 days after HTx presented positive PCR in 80% of cases. For every increase of 100 lymphocytes/mm3, the risk of PCR positivity was reduced by 26% (hazard rate ratio = 0.74; 95% confidence interval: 0.59 to 0.93, p = 0.009). CONCLUSION: There was an association between lymphopenia in the perioperative period of HTx and early T. cruzi parasitemia detected by PCR.

FUNDAMENTO: É desconhecido se a linfopenia é fator de risco para a reativação da doença de Chagas no transplante cardíaco (TxC), como recentemente descrito na reativação de citomegalovírus em pacientes transplantados. OBJETIVO: Avaliar se a linfopenia no perioperatório do TxC está relacionada à parasitemia precoce pelo Trypanosoma cruzi. MÉTODOS: Amostra analisada (janeiro de 2014 a janeiro de 2023) em estudo observacional e retrospectivo. A parasitemia foi avaliada nos primeiros 3 meses após o TxC por meio da reação em cadeia da polimerase sérica (PCR) e comparada com a contagem total de linfócitos no perioperatório do TxC por curvas ROC. Comparadas características de base com a PCR Chagas por modelos de risco proporcionais de Cox independentes. Nível de significância adotado de 5%. RESULTADOS: Amostra (n = 35) apresentou idade média de 52,5 ± 8,1 anos e PCR Chagas positiva em 22 pacientes (62,8%). As médias dos menores valores de linfócitos nos primeiros 14 dias do TxC foram 398 ± 189 e 755 ± 303 células/mm3 em pacientes com e sem parasitemia nos 3 meses após o TxC, respectivamente (área sob a curva = 0,857; intervalo de confiança de 95%: 0,996 a 0,718, sensibilidade e especificidade de 83,3% e 86,4%). Determinado valor de corte inferior a 550 linfócitos/mm3 como fator de risco para presença de parasitemia. Pacientes com linfócitos < 550 unidades/mm3 nos primeiros 14 dias do pós-TxC apresentaram PCR positiva em 80% dos casos. Para cada aumento de 100 linfócitos/mm3, o risco de positividade da PCR é reduzido em 26% (razão de riscos = 0,74; intervalo de confiança de 95%: 0,59 a 0,93, p = 0,009). CONCLUSÃO: Houve associação entre a linfopenia no perioperatório do TxC com a parasitemia precoce pelo T. cruzi detectada por PCR.

Circulating/cerebrospinal T lymphocytes as indicators of clinical prognosis in intracerebral hemorrhage: A prospective study.

Secondary injury of cerebral hemorrhage is induced by systemic inflammatory cascades, which are related to perihematomal brain edema, cellular apoptosis, and the disruption of the blood-brain barrier. This study was to specifically elaborate the relationship of circulating/cerebrospinal T lymphocytes and Glasgow Coma Scale (GCS) score at 6 months after intracerebral hemorrhage (ICH). The enrolled patients were divided into 2 groups based on GCS score: the favorable prognosis group (GCS > 12) and unfavorable prognosis group (GCS ≤ 12). T lymphocyte subpopulations were analyzed by flow cytometry. A total of 30 samples of peripheral blood and 17 samples of cerebrospinal fluid were collected and analyzed, including 19 cases and 12 cases in the favorable prognosis group (GCS > 12) respectively. Both CD3+ and CD3+CD4+ T lymphocyte counts on Day 1 after ICH were lower in the peripheral blood of patients with unfavorable prognosis (GCS ≤ 12) (P = .025 and .022, respectively). There were correlation trends between the GCS scores and CD3+ T lymphocyte count (P = .0144), and CD3+CD4+ T lymphocyte count (P = .0135). In cerebrospinal fluid, there was a close correlation between the GCS scores and CD3+CD4+ percentage, CD4+/CD8+ ratio, CD3+ and CD3+CD4+ T lymphocyte counts. The area under the curve of CD4+/CD8+ T lymphocyte ratio was the largest among them (P = .000 and area under the curve = 0.917), with a significantly high specificity and sensitivity (0.917 and 1.000). Based on cerebrospinal fluid samples, the CD4+/CD8+ T lymphocyte ratio on Day 1 after ICH may be a more significant indicator to predict the short-term prognosis at 6 months after ICH.

Prognostic value of systemic immune-inflammation index, neutrophil-lymphocyte ratio, and thrombocyte-lymphocyte ratio in critically ill patients with moderate to severe traumatic brain injury.

Traumatic brain injury (TBI) is a significant health problem with a high mortality rate. Inflammatory markers can predict the prognosis of TBI where neuroinflammation is essential. In this study, the prognostic value of the systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) at admission in patients with critical TBI was investigated. Patients with moderately severe TBI in the intensive care unit (ICU) of a tertiary center between June 2020 and June 2022 were retrospectively reviewed. Patients were classified into survivor and mortality groups. The predictive performance of SII, PLR, and NLR levels calculated from blood results at admission and 28-day mortality and patient outcomes were analyzed. One hundred sixty-one patients were included in this study. The median age of the entire population was 41 (18-90) years, and 80.7% (n = 130) of the patients were male. Falls (42.2%) and traffic accidents (40.4%) were the most common causes of TBI. The most common primary diagnoses in patients with TBI were acute subdural hematoma (30.4%) and subarachnoid hemorrhage (26.1%). The SII and NLR levels were significantly higher in the mortality group, and PLR levels were significantly lower (P = .004, P < .001, P < .001, respectively). In multivariate regression analysis, SII and PLR were independent predictors of mortality (P = .031 and P < .001, respectively). In the receiver operating characteristics (ROC) curve analysis, the cutoff value for SII was ≥ 2951, and the area under the curve (AUC) was 0.662 (95% CI, 0.540-0.784). The cutoff value for NLR was ≥ 9.85, AUC was 0.717 (95% CI, 0.600-0.834), and the cutoff value for PLR was ≤ 130.4, AUC was 0.871 (95% CI, 0.796-0.947). 28-day mortality was 21.1%. Neuroinflammation is essential in patients with critical TBI, and inflammatory markers SII, NLR, and PLR have prognostic importance. SII and PLR are independent predictors of mortality. Early detection of those with a poor prognosis in critically ill TBI patients and planning aggressive treatments may contribute to reducing mortality.

Biomarker of severity in hospitalised patients with COVID-19: a retrospective study.

BACKGROUND: The novel COVID-19 was rapidly spreading and was highly contagious. COVID-19 caused over 6 million deaths worldwide, with high mortality rates, particularly in severe cases. OBJECTIVE: This study aimed to investigate whether serum albumin-neutrophil count to lymphocyte count ratio (NLR) score (ANS) could be used as a prognostic indicator of COVID-19 severity. DESIGN: A retrospective study. PARTICIPANTS: Based on the WHO diagnostic criteria, patients were classified as either non-severe (n=270) or severe (n=100). PRIMARY AND SECONDARY OUTCOME MEASURES: NLR, serum albumin level and ANS. MAIN RESULTS: The NLR of patients with severe disease was significantly higher than that of those with non-severe disease. Serum albumin levels were significantly lower in patients with severe disease than in those with non-severe disease. The cut-off values representing the maximum potential effectiveness of serum albumin and NLR were 33.5 g/L and 8.25, respectively, according to the Youden index. In patients with severe COVID-19, we observed that the serum albumin level, NLR and ANS were independent prognostic indicators of severe COVID-19 using logistic analysis. The relative risk of severe COVID-19 was 7.65 (95% CI 3.72 to 15.75, p<0.05) in the ANS 2 group compared with that in ANS 0. CONCLUSIONS: ANS could be used as a prognostic indicator of COVID-19 severity.

Prognostic value of sarcopenia and inflammatory indices synergy in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapy.

BACKGROUND AND PURPOSE: Sarcopenia has been demonstrated to be adversely correlated with the prognosis of various cancers. Our study aimed to estimate the prognostic value of sarcopenia in conjunction with inflammatory indices [neutrophil-to-lymphocyte ratio (NLR)] for evaluating the prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing chemoradiotherapy. MATERIALS AND METHODS: This study retrospectively analyzed 255 patients with ESCC who received chemoradiotherapy from January 2012 to December 2018. Multivariate Cox regression analysis was employed to identify prognostic values of assessed factors following a novel prognostic scoring system (SMI-NLR), covering sarcopenia and NLR during different treatment courses. RESULTS: Kaplan-Meier analysis revealed significantly greater overall survival (OS) rates in the nonsarcopenia group than in the sarcopenia group (P = 0.011). The low NLR group (< 4.84) demonstrated significantly higher OS rates than the high NLR group (≥ 4.84) (P < 0.001). The SMI-NLR prognostic model was established through multivariate analysis, revealing that Karnofsky performance status [hazard ratio (HR) = 0.285; 95% confidence interval (CI) = 0.117-0.699; P = 0.006], clinical staging (HR = 5.223; 95% CI = 1.879-14.514; P = 0.002), and preSMI-NLR (HR = 0.544; 95% CI = 0.330-0.898; P = 0.017) were independent factors affecting the prognosis of patients with ESCC. Nomograms were constructed based on these data providing more accurate 1-, 3-, and 5-year survival rates for patients with ESCC. CONCLUSION: Our study indicates the effectiveness of the combined sarcopenia and NLR prognostic model for the prognostic evaluation of patients with ESCC having undergone chemoradiotherapy.