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.

Vitamin D3 (Calcitriol) Monotherapy Decreases Tumor Growth, Increases Survival, and Correlates with Low Neutrophil-to-Lymphocyte Ratio in a Murine HPV-16-Related Cancer Model.

Vitamin D3 or calcitriol (VitD3) has been shown to have anticancer and anti-inflammatory activity in in vitro models and clinical studies. However, its effect on HPV-16-related cancer has been sparsely explored. In this study, we aimed to determine whether monotherapy or combination therapy with cisplatin (CP) reduces tumor growth and affects survival and systemic inflammation. Treatments were administered to C57BL/6 mice with HPV-16-related tumors (TC-1 cells) as follows: (1) placebo (100 µL vehicle, olive oil, orally administered daily); (2) VitD3 (3.75 µg/kg calcitriol orally administered daily); (3) CP (5 mg/kg intraperitoneally, every 7 days); and (4) VitD3+CP. Tumor growth was monitored for 25 days, survival for 60 days, and the neutrophil-to-lymphocyte ratio (NLR) was evaluated on days 1 (baseline), 7, and 14. VitD3+CP showed greater success in reducing tumor volume compared to CP monotherapy (p = 0.041), while no differences were observed between CP and VitD3 monotherapy (p = 0.671). Furthermore, VitD3+CP prolonged survival compared to CP (p = 0.036) and VitD3 (p = 0.007). Additionally, at day 14 the VitD3 and VitD3+CP groups showed significantly lower NLR values than the CP group (p < 0.05, for both comparisons). Vitamin D3 could be a promising adjuvant in the treatment of cervical cancer or solid tumors and deserves further investigation.

Can direct bilirubin-to-lymphocyte ratio predict surgery for pediatric adhesive small bowel obstruction?

OBJECTIVE: Estimating which patients might require surgical intervention is crucial. Patients with complete bowel obstructions exhibit disrupted enterohepatic cycles of bile and bacteremia due to bacterial translocation. The goal of this study was to develop a prediction index using laboratory inflammatory data to identify patients who may need surgery. MATERIALS AND METHODS: The patients were divided into two groups based on their management strategy: Non-operative management (Group 1) and surgical management (Group 2). RESULTS: The indirect bilirubin, direct bilirubin, and total bilirubin were significantly higher in Group 2 than in Group 1 (p = 0.001, p < 0.001, and p < 0.001, respectively). The neutrophil-to-lymphocyte ratio (NLR), platelet-to-NLR (PNLR), and direct bilirubin-to-lymphocyte ratio (DBR) were significantly higher in Group 2 compared to Group 1 (p = 0.041, p = 0.020, and p < 0.001, respectively). In group 2, 78% have viable bowels. Resection was performed in 40% of cases, with 12% mortality and a 10-day average hospital stay. DLR performs the best overall accuracy (72%), demonstrating a well-balanced sensitivity (62%) and specificity (81%). CONCLUSIONS: This study suggested that DBR is a more accurate predictive index for surgical intervention in pediatric adhesive small bowel obstruction patients compared to NLR and PNLR, providing valuable guidance for treatment strategies.

OBJETIVO: Desarrollar un índice de predicción utilizando datos inflamatorios de laboratorio para identificar qué pacientes podrían necesitar cirugía. MÉTODO: Los pacientes se dividieron en dos grupos según su estrategia de manejo: no quirúrgico (grupo 1) o quirúrgico (grupo 2). RESULTADOS: Las bilirrubinas indirecta, directa y total fueron significativamente más altas en el grupo 2 que en el grupo 1 (p = 0.001, p < 0.001 y p < 0.001, respectivamente). Las relaciones neutrófilos-linfocitos, plaquetas-neutrófilos-linfocitos y bilirrubina directa-linfocitos fueron significativamente más altas en el grupo 2 que en el grupo 1 (p = 0.041, p = 0.020 y p < 0.001, respectivamente). En el grupo 2, el 78% tenían intestino viable. Se realizó resección en el 40% de los casos, con un 12% de mortalidad y una estancia hospitalaria promedio de 10 días. La relación bilirrubina directa-linfocitos tuvo la mejor precisión general (72%), demostrando una sensibilidad bien equilibrada (62%) y una buena especificidad (81%). CONCLUSIONES: Este estudio sugiere que la relación bilirrubina directa-linfocitos es un índice predictivo más preciso para la intervención quirúrgica en pacientes pediátricos con obstrucción adhesiva de intestino delgado en comparación con la de neutrófilos-linfocitos y la de plaquetas-neutrófilos-linfocitos, proporcionando una valiosa orientación para las estrategias de tratamiento.

Prognostic value of systemic inflammation response indexes obtained from the complete blood count in patients treated for advanced ovarian carcinoma in front line.

OBJECTIVE: Various systemic inflammation response indexes (SIRI) have repeatedly been described as prognostic factors in ovarian cancer. They have not been validated in prospective trials and published results are sometimes contradictory. We aimed to explore their role in a cohort of patients diagnosed with stage III and IV ovarian cancer treated at our institution. METHODS: We retrospectively examined the prognostic influence of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR), the red cell distribution width (RDW), and the mean platelet volume (MPV). RESULTS: A total of 77 patients were analyzed. NLR > 2.243 at diagnosis, NLR before primary surgery, MLR at diagnosis, PLR > 289.1 at diagnosis, and PLR at diagnosis were significant in univariate Cox regression for progression-free survival, but none of them retained their significance in the multivariate Cox regression analysis. For overall survival, NLR > = 2.53 at diagnosis, MLR > = 0.245 at diagnosis, and PLR > = 198.3 at diagnosis resulted significant in univariate COX regression; only PLR > = 198.3 at diagnosis retained its significance in the multivariate analysis. CONCLUSION: In our cohort, PLR > = 198.3 was an independent prognostic factor for worse OS. The definitive role of SIRI in ovarian cancer has not yet been established. If their value as prognostic factors could finally be established, they would become a simple and economical method to predict prognosis in patients with advanced ovarian cancer. Therefore, it is time to conduct prospective, multicenter studies with larger samples to definitively establish its role in ovarian cancer, if any.

[Neutrophil-to-lymphocyte ratio as a predictor of intestinal resection in incarcerated inguinal hernias]. / Otnoshenie neitrofilov k limfotsitam kak prediktor rezektsii kishki u bol'nykh s ushchemlennymi pakhovymi gryzhami.

INTRODUCTION: Inguinal hernia is defined as a projection of an organ through the inguinal canal. This can be incarcerated as a consequence of continuous inflammation of the hernial sac, which will prevent its return, causing damage to the venous and lymphatic return of the viscera. The neutrophil-to-lymphocyte ratio (NLR) is an easily accessible inflammatory biomarker obtained from blood cell counts. Therefore, the objective was to determine if the NLR is useful as a predictor of intestinal resection in incarcerated inguinal hernias. MATERIAL AND METHOD: An observational, analytical, diagnostic test and retrospective study was carried out in a hospital in northern Peru from January 2013 to August 2019 in the Department of General Surgery and Emergency Surgery and Critical Care. Patients diagnosed with unilateral inguinal hernia with intestinal obstruction were included. For the relationship between the event and the exposure, it was analyzed using Chi square (χ2) and T-Student. The sensitivity, specificity, positive predictive value, negative predictive value of the NLR as well as the area under the ROC curve were found to determine the predictive accuracy. RESULTS: 161 patients with incarcerated inguinal hernia were studied: group I (20 patients with intestinal resection) and group II (141 patients without intestinal resection). The mean age in groups I and II were 69±16 and 60±17 years (p<0.05); the frequency in males was 70% in group I and 76% in group II (p>0.05). Intestinal obstruction and duration of incarceration >24 hours and the platelet-to-lymphocyte ratio demonstrated significant differences. With respect to NLR taking a cut-off point ≥6.5, a sensitivity of 75%, a specificity of 93.62%, a positive predictive value of 62.5% and a negative predictive value of 96.35% were observed; In addition, when analyzing with the ROC curve, a value of 5.14 was obtained as a predictor of intestinal resection with a sensitivity of 90% and a specificity of 84.4% (p<0.001). Therefore, the NLR >5.14 predicts intestinal resection in patients with incarcerated inguinal hernias with an area under the curve of 0.92 at the Belen Hospital of Trujillo. CONCLUSIONS: The neutrophil-to-lymphocyte ratio is useful for predicting intestinal resection with a diagnostic accuracy of 92%.

Clinicopathological Aspects and Inflammation-Immune Markers in Alcohol and/or Hepatitis C Virus-Induced Hepatocellular Carcinoma Patients Treated With Sorafenib.

Background: Tyrosine kinase inhibitors have been used to treat hepatocellular carcinoma (HCC), but the outcomes of patients under treatment vary. Since the roles of clinicopathological aspects and markers of chronic inflammation/immune homeostasis in the outcome of HCC patients treated with sorafenib are still unclear, these were the aims of this study. Methods: Patients with alcohol-induced and/or hepatitis C virus (HCV)-induced HCC (n = 182) uniformly treated with sorafenib were included in the study. Baseline clinicopathological aspects of patients were computed from the medical records. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII) were obtained from the hematological exam performed before the administration of sorafenib. Overall survival (OS) was analyzed using Kaplan-Meier probabilities, log-rank test, and univariate and multivariate Cox proportional hazard ratio (HR) analyses. Results: In multivariate analysis, alpha-foetoprotein (AFP) level and Child-Pugh score were predictors of OS. Patients with AFP levels higher than 157 ng/mL and Child-Pugh B or C had 1.40 (95% confidence interval (CI): 1.03 - 1.91, P = 0.03) and 1.64 (95% CI: 1.07 - 2.52, P = 0.02) more chances of evolving to death than the remaining patients, respectively. NLR, PLR, LMR, SIRI, and SII did not alter the OS of HCC patients. Conclusions: AFP level and Child-Pugh score act as independent prognostic factors in patients with alcohol and/or HCV-induced HCC treated with sorafenib, but markers of chronic inflammation/immune homeostasis seem not to alter the outcome of patients with HCC induced by alcohol and/or HCV.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as biomarkers to prognosticate survival in advanced gastric cancer patients in the era of immunotherapy: a systematic review and meta-analysis.

Background: Gastric cancer (GC) remains an important global health concern with limited treatment options for advanced cases. Immunotherapy has shown promising results, but identifying predictive biomarkers for treatment efficacy is challenging. Novel inflammatory markers, such as the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), derived from complete blood count measurements, have gained attention as potential prognostic indicators. This systematic review and meta-analysis investigates the roles of the PLR and NLR as predictors of overall survival (OS) and progression-free survival (PFS) in advanced GC and gastroesophageal junction cancer (GEJC) patients treated with immunotherapy. Methods: A comprehensive search of the literature was conducted through PubMed, Embase, and Cochrane Library to identify relevant studies. A total of 16 studies involving NLR and 8 studies involving PLR were included. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between high biomarker values and poor OS and PFS. Subgroup analyses were performed to explore potential sources of heterogeneity. Poor OS, PFS were defined by each study as statistically significant shorter survival. Results: A high NLR was significantly associated with worse OS (HR: 2.11; 95% CI: 1.70-2.62) and PFS (HR: 1.76; 95% CI: 1.43-2.17). High PLR was also significantly associated with poorer OS (HR: 1.77; 95% CI: 1.44-2.17) and PFS (HR: 1.61; 95% CI: 1.33-1.96). Subgroup analyses and sensitivity analyses supported the robustness of these findings. Publication bias was noted in NLR analysis for OS but not for PFS. PLR analysis showed low publication bias. Conclusions: Elevated NLR and PLR are associated with unfavorable OS and PFS outcomes in advanced GC/GEJC patients on immunotherapy. These findings imply the utility of these easily accessible biomarkers in prognostic assessment. However, standardized cutoff values and further research on interactions with the tumor microenvironment and comorbidities are needed. Additional prospective studies are warranted to validate these findings for both biomarkers.

Identification of prognostic factors for survival in patients with metastatic gastric adenocarcinoma in a Mexican population.

INTRODUCTION AND AIMS: Gastric adenocarcinoma is among the high-ranking tumors, with respect to frequency and mortality, worldwide. The inflammatory process and immune system activity are associated with oncologic control. Our aim was to identify whether the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and other variables are prognostic factors for survival in patients with metastatic gastric cancer in a Mexican population. MATERIAL AND METHODS: Patients diagnosed with metastatic gastric adenocarcinoma, hospitalized within the time frame of December 2011 to 2021, were analyzed. The NLR, PLR, and albumin and hemoglobin levels obtained from blood samples were calculated. Functional status (ECOG and Karnofsky), sex, histology, and the presence of signet ring cells were also considered possible prognostic factors. Each factor's prognostic value for overall survival was determined through univariate and multivariate analyses. RESULTS: The study included 956 patients diagnosed with metastatic gastric cancer, of whom 494 (51.7%) were men and 462 (48.3%) were women. The main histologic finding was diffuse adenocarcinoma (n = 619, 64.7%), followed by intestinal adenocarcinoma (n = 293, 30.6%), and the presence of signet ring cells was found in 659 (68.9%) patients. Diagnostic laparoscopy was performed on 238 patients (24.9%) to confirm peritoneal carcinomatosis. The multivariate analysis showed that an NLR above 3.2 (HR 1.51, 95% CI 1.27-1.8; p < 0.001), albumin below 3.5 g/dl (HR 1.25, CI 1.06-1.47; p = 0.006), and an ECOG performance status of 2 or higher (HR 1.39, CI 1.10-1.76; p = 0.005) were independent factors that predicted a lower survival rate, whereas a Karnofsky score above 70% (HR 0.69, CI 0.53-0.91; p = 0.008) was associated with a better survival rate. Lastly, the PLR was not statistically significant in the multivariate analysis. CONCLUSIONS: The NLR, nutritional status assessed through albumin measurement, and functional status can act as independent prognostic survival factors in hospitalized Mexican patients diagnosed with metastatic gastric adenocarcinoma and be taken into account during therapeutic decision-making.

Neutrophil to lymphocyte ratio and systemic immune-inflammatory index as markers of response to autologous hematopoietic stem cell transplantation in persons with multiple sclerosis.

INTRODUCTION: Biomarkers that help to evaluate the immune system and could be useful in multiple sclerosis (MS) are the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII). The objective of this work is to evaluate the significance of the SII index, PLR, and NLR before and after transplantation in individuals with MS who underwent autologous hematopoietic stem cell transplant (aHSCT) at a single institution. METHODS: Patients with MS who received an aHSCT between 2017 and 2022 were included in the study. NLR, PLR, and SII index were calculated prior to the transplant and 100 days after, and evaluation of the expanded disability status scale (EDSS) was done before the transplant and 12 months after. The cohort was divided into two groups: aHSCT responders (R) and nonresponders (NR). RESULTS: Fifty-eight individuals were examined: 37 patients in the responders group R group and 21 in NR group. There was no statistically significant difference in the SII, NLR, and PLR prior to the transplant, however at 100 days post-HSCT, NLR in the R group was 1.8 versus 3.1 in the NR group (p = 0.003), PLR was 194 versus 295, respectively (p = 0.024), meanwhile SII index was 489.5 versus 729.3 (p < 0.001). CONCLUSION: High NLR and SII index values after the aHSCT were associated with a worsening in the EDSS score. However, since this is the first ever study that compared NLR and SII index with the aHSCT response in persons with MS, further studies must be performed to corroborate this information.

Development of a Prognostic Model for Early Breast Cancer Integrating Neutrophil to Lymphocyte Ratio and Clinical-Pathological Characteristics.

BACKGROUND: Breast cancer-related inflammation is critical in tumorigenesis, cancer progression, and patient prognosis. Several inflammatory markers derived from peripheral blood cells count, such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) are considered as prognostic markers in several types of malignancy. METHODS: We investigate and validate a prognostic model in early patients with breast cancer to predict disease-free survival (DFS) based on readily available baseline clinicopathological prognostic factors and preoperative peripheral blood-derived indexes. RESULTS: We analyzed a training cohort of 710 patients and 2 external validation cohorts of 980 and 157 patients with breast cancer, respectively, with different demographic origins. An elevated preoperative NLR is a better DFS predictor than others scores. The prognostic model generated in this study was able to classify patients into 3 groups with different risks of relapse based on ECOG-PS, presence of comorbidities, T and N stage, PgR status, and NLR. CONCLUSION: Prognostic models derived from the combination of clinicopathological features and peripheral blood indices, such as NLR, represent attractive markers mainly because they are easily detectable and applicable in daily clinical practice. More comprehensive prospective studies are needed to unveil their actual effectiveness.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on postoperative day three as a biochemical predictor of clinically significant pancreatic fistula in patients undergoing distal pancreatectomy.

INTRODUCTION AND AIMS: Distal pancreatectomy is a frequent procedure and postoperative fistula, its most common complication, has an incidence of 30 to 60%. The aim of the present work was to study the role of the neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio, as indicators of inflammatory response in the setting of pancreatic fistula. METHODS: A retrospective observational study was conducted on patients that underwent distal pancreatectomy. The diagnosis of postoperative pancreatic fistula was made according to the definition proposed by the International Study Group on Pancreatic Fistula. The relation of postoperative pancreatic fistula to the neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio was determined in the postoperative evaluation. SPSS v.21 software was utilized for the statistical analysis and a P<.05 was considered statistically significant. RESULTS: A total of 12 patients (27.2%) developed grade B or grade C postoperative pancreatic fistula. ROC curves were constructed and a threshold of 8.3 (PPV 0.40, NPV 0.86) was established for the neutrophil-to-lymphocyte ratio, with an area under the curve of 0.71, sensitivity of 0.81, and specificity of 0.62, whereas a threshold of 33.2 (PPV 0.50, NPV 0.84) was established for the platelet-to-lymphocyte ratio, with an area under the curve of 0.72, sensitivity of 0.72, and specificity of 0.71. CONCLUSION: The neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio are serologic markers that can aid in identifying patients that will present with grade B or grade C postoperative pancreatic fistula, thus helping to provide an opportune focus on care and resources.

Immature granulocytes and neutrophil-to-lymphocyte ratio as markers of treatment response in subacute thyroiditis

ABSTRACT Objective Subacute thyroiditis is also known as subacute granulomatous thyroiditis, giant cell thyroiditis, painful thyroiditis, and De Quervain's thyroiditis. Immature granulocytes (IG) and neutrophil-to-lymphocyte ratio (NLR) are new inflammatory markers that are easily detected in routine complete blood count (CBC) tests. The aim of this study was to investigate the role of IG and NLR as markers of treatment response in patients with subacute thyroiditis. Subjects and methods The study included 41 patients with subacute thyroiditis treated and monitored in our outpatient clinic between April 2020 and April 2022. From a retrospective review of medical records, we recorded results of IG, NLR, thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) from blood tests obtained routinely before and after treatment. Results Overall, 31 (75.6%) patients were women and 10 (21.4%) were men. The median age was 41 years (range 22-68 years). The laboratory tests showed the following median (range) results: IG, 0.03 (0.01-0.08); NLR, 3.6 (1.2-5.2); TSH, 0.02 mIU/L (0.01-3.35 mIU/L); fT4, 2.3 ng/dL (1.0-7.0 ng/dL); fT3, 5.6 pmol/L (2.6-15.2 pmol/L); ESR, 49 mm/h (17.0-87 mm/h); and CRP, 73 mg/dL (3.0-188 mg/dL). Conclusion Early diagnosis and treatment of subacute thyroiditis is fundamental. In the present study, the new inflammatory markers IG and NLR, measured routinely on CBC tests, decreased significantly after subacute thyroiditis treatment relative to pretreatment values. After treatment, the NLR change correlated with ESR and CRP changes, while the IG change correlated only with CRP change. These findings suggest that the markers IG and NLR may be used to evaluate treatment response in patients with subacute thyroiditis.

Segmented neutrophil-to-monocyte ratio and systemic immune-inflammation index associated with the severity and functional prognosis of acute ischemic stroke.

PURPOSE/AIM OF THE STUDY: To identify the inflammation indexes associated with the severity and functional prognosis in ischemic stroke. MATERIAL AND METHODS: A prospective study was conducted with ischemic stroke cases included in the i-ReNe clinical registry. Patients were divided into groups according to the severity on admission measured by the National Institutes of Health Stroke Scale (NIHSS) and the functional prognosis at 30 and 90 days of discharge measured by the modified Rankin Scale (mRS). RESULTS: We included 145 patients with a mean age of 61.5 ± 12.75, 97 (66.9%) were men. The leukocyte and neutrophil counts, Neutrophil-to-Lymphocyte ratio (NLR), Derived Neutrophil-to-Lymphocyte ratio (dNLR), Platelet-to-Lymphocyte ratio (PLR), Segmented Neutrophil-to-Monocyte ratio (SeMo ratio), and Systemic Immune-inflammation index (SII) were higher in moderate-to-severe stroke (NIHSS ≥6). NLR, PLR, SeMo ratio, and SII were higher in the group with severe disability and death at 30 days (mRS ≥4). In the multiple logistic regression analyses, SeMo ratio >14.966 and SII >623.723 were associated with moderate-to-severe stroke (NIHSS ≥6). In addition, SeMo ratio >7.845 was associated with severe disability and death at 30 days (mRS ≥4). CONCLUSIONS: Systemic inflammation indexes could be rapid and low-cost markers used in the initial evaluation of ischemic stroke, whose values could help to stratify patients according to their severity and functional prognosis. This is the first study to establish a relationship between ischemic stroke and the SeMo ratio.

Decrease in cognitive performance and increase of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with higher doses of antipsychotics in women with schizophrenia: a cross-sectional study.

BACKGROUND: We explored the relationship between symptoms, cognitive performance, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) (three markers of inflammation), and antipsychotic dose (in chlorpromazine units) in male and female patients with schizophrenia. METHODS: We conducted a cross-sectional analysis in patients with schizophrenia of the complete blood count and the results of neuropsychological testing, using the Welch t-test to compare groups and the Pearson test for correlations. RESULTS: We found that the NLR and the PLR are higher among women with schizophrenia when compared with men. In women, the NLR and the PLR correlate positively with antipsychotic drug dose and inversely with a working memory test (Direct Digit Span). Higher doses of antipsychotics are associated with worse working and semantic memory and mental flexibility in the women in our sample. CONCLUSION: Higher doses of antipsychotics were associated with worse working and semantic memory and mental flexibility in women with schizophrenia. No such correlations were present in men, suggesting that, in female patients, cognitive performance deteriorates as the antipsychotic dose is increased, a finding that could be mediated by inflammatory mechanisms, given the demonstrated relationship to biomarkers of inflammation - e.g., the NLR and the PLR. TRIAL REGISTRATION: NCT03788759 (ClinicalTrials.gov).

Could a simple biomarker as neutrophil-to-lymphocyte ratio reflect complex processes orchestrated by neutrophils?

The complex pathological mechanisms of autoimmune diseases have now been discovered and described, including interactions between innate and adaptive immunity, the principal cells of which are neutrophils and lymphocytes. Neutrophil-to-lymphocyte ratio (NLR) was proposed as a biomarker for inflammation that reflects the balance between these aspects of the immune system. NLR is widely studied as a prognostic or screening parameter in quantity diseases with important inflammatory components such as malignancies, trauma, sepsis, critical care pathology, etc. Although there are still no consensually accepted normal values for this parameter, there is a proposal to consider an interval of 1-2 as a normal value, an interval of 2-3 as a grey area indicating subclinical inflammation and values above 3 as inflammation. On the other hand, several studies have been published indicating that a particular morphological type of neutrophils, low-density neutrophils (LDNs), play a pathological role in autoimmune diseases. Probably, the LDNs detected in patients with different autoimmune diseases, mostly than normal density neutrophils, are involved in the suppression of lymphocytes through different pathways: inducing of lymphopenia through neutrophil depending overproduction of type I interferon (IFN)-α/ß and direct suppression by a hydrogen-peroxide-dependent mechanism. Their functional features involvement in IFN production is of particular interest. IFN is one of the critical cytokines in the pathogenesis of many autoimmune diseases, primarily systemic lupus erythematosus (SLE). An interesting and important feature of IFN involvement in the pathogenesis of SLE is not only to be directly related to lymphopenia but also its role in the inhibition of the production of C-reactive protein (CRP) by hepatocytes. The CRP is the primary acute phase reactant, which in SLE often does not correlate with the extent of inflammation. NLR in such a case can be an important biomarker of inflammation. The study of NLR as a biomarker of inflammation also deserves attention in other diseases with established interferon pathways, as well as in hepatopathies, when CRP does not reflect the proper inflammation activity. Also, it may be interesting to study its role as a predictor of relapses in autoimmune diseases.

Testosterone immunomodulation in free-living and captive Rhinella icterica male toads.

Testosterone (T) regulates immune function, with both immunostimulatory and immunosuppressive effects on several vertebrates. We investigated the covariation between plasma T and corticosterone (CORT) levels and immunity (plasma bacterial killing ability (BKA), and neutrophil to lymphocyte ratio (NLR)) in free-living Rhinella icterica male toads inside and outside the reproductive season. We found an overall positive correlation between steroids and immune traits, with toads during the reproductive season displaying increased T, CORT and BKA. We also investigated the T transdermal application effects on T, CORT, phagocytosis of blood cells, BKA and NLR in captive toads. Toads were treated with T (1, 10 or 100 µg) or vehicle (sesame oil) for eight consecutive days. Animals were bled on the first and eighth days of treatment. Increased plasma T was observed on the first and last day of T-treatment, while increased BKA was observed following all T doses on the last day, with a positive correlation between T and BKA. Plasma CORT, NLR and phagocytosis increased on the last day for all T-treated and vehicle groups. Overall, we demonstrated a positive covariation between T and immune traits in the field and T-induced augmented BKA in captive toads, indicating a T immunoenhancing effect in R. icterica males. This article is part of the theme issue 'Amphibian immunity: stress, disease and ecoimmunology'.

The neutrophil-to-lymphocyte ratio as a prognostic biomarker in Guillain-Barre syndrome: a systematic review with meta-analysis.

Background and objectives: Guillain-Barre syndrome (GBS) is an immune-mediated neuropathy. This has raised the possibility that the neutrophil-lymphocyte ratio (NLR) may be a biomarker of its activity. We conducted a systematic review and meta-analysis to summarize the evidence of NLR as a potential biomarker for GBS. Methods: We systematically searched databases (PubMed, Ovid-Medline, Embase, Scopus, Web of Science, SciELO Citation Index, LILACS, and Google Scholar) until October 2021 for studies evaluating pre-treatment NLR values in GBS patients. A meta-analysis using a random-effects model to estimate pooled effects was realized for each outcome and a narrative synthesis when this was not possible. Subgroup and sensitivity analysis were realized. GRADE criteria were used to identify the certainty of evidence for each result. Results: Ten studies from 745 originally included were selected. Regarding GBS patients versus healthy controls, a meta-analysis of six studies (968 patients) demonstrated a significant increase in NLR values in GBS patients (MD: 1.76; 95% CI: 1.29, 2.24; I2 = 86%) with moderate certainty due to heterogeneity of GBS diagnosis criteria used. Regarding GBS prognosis, assessed by Hughes Score ≥ 3, NLR had a sensitivity between 67.3 and 81.5 and a specificity between 67.3 and 87.5 with low certainty due to imprecision, and heterogeneity. In relation to respiratory failure, NLR had a sensitivity of 86.5 and specificity of 68.2 with high and moderate certainty, respectively. Discussion: With moderate certainty, mean NLR is higher in GBS patients compared to healthy controls. Furthermore, we found that NLR could be a prognostic factor for disability and respiratory failure with low and moderate certainty, respectively. These results may prove useful for NLR in GBS patients; however, further research is needed. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021285212.

Inflammation associated with lung function abnormalities in COVID-19 survivors.

BACKGROUND: Activation of inflammatory pathways promotes organ dysfunction in COVID-19. Currently, there are reports describing lung function abnormalities in COVID-19 survivors; however, the biological mechanisms remain unknown. The aim of this study was to analyze the association between serum biomarkers collected during and following hospitalization and pulmonary function in COVID-19 survivors. METHODS: Patients recovering from severe COVID-19 were prospectively evaluated. Serum biomarkers were analyzed from admission to hospital, peak during hospitalization, and at the time of discharge. Pulmonary function was measured approximately 6 weeks after discharge. RESULTS: 100 patients (63% male) were included (age 48 years, SD ± 14) with 85% having at least one comorbidity. Patients with a restrictive spirometry pattern (n = 46) had greater inflammatory biomarkers compared to those with normal spirometry (n = 54) including peak Neutrophil-to-Lymphocyte ratio (NLR) value [9.3 (10.1) vs. 6.5 (6.6), median (IQR), p = 0.027] and NLR at hospital discharge [4.6 (2.9) vs. 3.2 (2.9) p = 0.005] and baseline C-reactive protein value [164.0 (147.0) vs. 106.5 (139.0) mg/dL, p = 0.083). Patients with an abnormal diffusing capacity (n = 35) had increased peak NLR [8.9 (5.9) vs. 5.6 (5.7) mg/L, p = 0.029]; baseline NLR [10.0 (19.0) vs. 4.0 (3.0) pg/ml, p = 0.002] and peak Troponin-T [10.0 (20.0) vs. 5.0 (5.0) pg/ml, p = 0.011] compared to patients with normal diffusing capacity (n = 42). Multivariable linear regression analysis identified predictors of restrictive spirometry and low diffusing capacity, but only accounted for a low degree of variance in pulmonary function outcome. CONCLUSION: Overexpression of inflammatory biomarkers is associated with subsequent lung function abnormalities in patients recovered from severe COVID-19.

Early variation of inflammatory indexes refines prognostic prediction in patients with hepatocellular carcinoma under systemic treatment.

Prognostic markers in advanced hepatocellular carcinoma (HCC) are relevant for clinical decisions. Variations in inflammatory indexes, such as neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), may correlate with outcomes. In the present study, it was aimed to assess the prognostic role of inflammation indexes in patients with HCC and the evolutionary behavior of these variables within the first month of treatment in a cohort of patients treated with sorafenib from 2009-2021. Subgroups were divided based on the median of each variable ('low' or 'high)'. Survival was estimated using the Kaplan-Meier method. Hazard Ratio (HR) with 95% confidence interval (CI) were estimated using Cox regression models. A total of 373 patients were included, most Child-Pugh-A (83.1%) and BCLC-C (74%). Child-Pugh-A (P=0.011), performance status 0 (P<0.001), no ascites (P<0.001) and NLR<2.6 (P<0.001) were independently associated with improved survival. Baseline PLR was not correlated with survival (P=0.137). Patients who maintained low NLR at baseline and at 1 month (reference subgroup) had improved survival (18.6 months, 95% CI:15.4-22.0) compared with the subgroup that maintained high NLR at baseline and at 1 month (4.2 months, 95% CI:3.6-5.9), with HR: 3.80 (95% CI: 2.89-4.96). The subgroup with low NLR at baseline and high NLR at 1 month had a worse prognosis compared with the reference group (HR:1.4, 95% CI: 1.1-2.0), whereas the subgroup with high NLR at baseline and low at 1 month had similar outcome (HR:1.2, 95% CI: 0.8-1.6). It was concluded that evolutionary variation of NLR has a prognostic role in HCC patients under systemic therapy. This finding suggested that systemic inflammation and early modulation of the immune environment during treatment may correlate with outcomes.

Right-sided acute diverticulitis in the West: experience at a university hospital in Argentina.

PURPOSE: In the West, diverticular disease is located mainly in the left colon. However, it can also present in the right colon, with an incidence of 1% to 2% in Caucasians. The purpose of this study was to describe our experience in right-sided acute diverticulitis (RD). METHODS: In this retrospective study, 410 patients with acute diverticulitis treated from 2013 to 2020 were included in a university hospital in Córdoba, Argentina. Colonic diverticulitis was stratified into 2 groups; RD and left-sided acute diverticulitis. Demographic and clinical variables, laboratory and imaging findings, type of treatment, follow-up, and recurrence were analyzed. RESULTS: Sixteen patients (3.9%) with RD were identified; 62.5% were male and the mean age was 40.7±11.7 years. A total of 81.3% were Caucasian and 18.7% Native American. Significant differences were found between both groups of diverticulitis; patients with RD were younger (P=0.001), with lower BMI (P=0.01), comorbidity rate (P=0.01), Charlson comorbidity index (P=0.02), hospital stay (P=0.01), severity according to the Hinchey classification (P=0.001) and had a lower recurrence rate (P=0.001). There were no significant differences in sex (P=0.95), duration of pain until admission (P=0.05), laboratory findings (P=0.23) and treatment (P=0.34). CONCLUSION: Conservative treatment predominated in RD, with a lower rate of complications and recurrences, providing data that support conservative therapy as initial treatment in RD in our environment.