Markers Of Systemic Inflammatory Response Research Articles

Regional use of extracellular microvesicles of mesenchymal stromal cells in acute necrotizing pancreatitis in an experiment

Background. The significance of the problem of treatment of acute pancreatitis is due to an increase in the incidence with an increase in the number of necrotizing forms, accompanied by a high incidence of severe complications and high mortality.Objective. To identify the impact of regionally used extracellular microvesicles of mesenchymal stromal cells on the endogenous intoxication markers in acute necrotizing pancreatitis in the experiment.Material and methods. Acute pancreatitis was induced by the introduction of a 0.3 ml of 5% solution of non-ionic polyethylene glycol octylphenol ether detergent into the caudal part of the rat pancreas. The study was conducted on 42 adult Wistar rats, which were randomly divided into 4 groups. Group I (n=6) included intact animals, Group II (control group) (n=12) included rats with pancreatitis without treatment, Group III (n=12) consisted of rats with pancreatitis treated with analgesia + infusions of 0.9% sodium chloride solution (saline), Group IV (n=12) included rats with pancreatitis treated with analgesia+ saline infusions + regional application of extracellular microvesicles of mesenchymal stromal cells. Cells were obtained from the bone marrow of healthy animals. Microvesicles were obtained by differential centrifugation under sterile conditions. Microvesicles were administered one day after the pancreatitis induction through the catheter installed into the pathologically altered part of the pancreas. The dose of microvesicles was calculated as equivalent to (derived from) 1 million mesenchymal stromal cells. The hematological parameters, markers of the systemic manifestation of the pathological process (alpha-amylase, aspartate aminotransferase, alanine aminotransferase), the endogenous intoxication markers (lipid peroxidation activity, nitric oxide level), the systemic inflammatory response markers (tumor necrosis factor-alpha, interleukin-6) were studied on the 3rd and 7th day from the start of disease modeling.Results. Regional use of extracellular microvesicles of mesenchymal stromal cells in the treatment of acute experimental necrotizing pancreatitis at an early stage helped to normalize the level of blood platelets, reduce enzymeemia, elements of endogenous intoxication (interleukin-6, tumor necrosis factor-alpha), and the nitric oxide level.Conclusion. The early application of extracellular microvesicles of mesenchymal stromal cells in the treatment of acute necrotizing pancreatitis in an experiment has a positive effect on parameters, which are key links of pathogenesis and leading markers of this disease severity.

Impact of C-reactive Protein-to-albumin Ratio on Lung Cancer With Interstitial Pneumonia

BackgroundLung cancer with interstitial pneumonia is known to be a refractory disease. We explored whether systemic inflammatory response markers are associated with outcomes in these patients. MethodsThe participants of this multicenter retrospective study, consisting of 17 medical institutions, were treatment-naïve patients with lung cancer combined with interstitial pneumonia who underwent surgical resection between 2012 and 2017. We reviewed clinicopathologic characteristics, including systemic inflammatory response markers, and examined the relationship between these characteristics and postoperative survival. ResultsAccording to the inclusion criteria, the final cohort consisted of 181 patients. Among preoperative systemic inflammatory response markers, the C-reactive protein-to-albumin ratio was an independent prognostic factor in multivariable analysis (hazard ratio, 1.71; P = .018). We examined whether the C-reactive protein-to-albumin ratio could be a determining factor in selecting surgical procedures (wedge resection or segmentectomy/lobectomy) preoperatively for patients with early-stage lung cancer. Although not statistically significant, there is a trend that the C-reactive protein-to-albumin ratio can be a possible determining factor in selecting surgical procedures. ConclusionsOur results indicate that the C-reactive protein-to-albumin ratio is an independent prognostic factor for overall survival in treatment-naïve patients with lung cancer combined with interstitial pneumonia.

Correlation between Neurotransmitters (Dopamine, Epinephrine, Norepinephrine, Serotonin), Prognostic Nutritional Index, Glasgow Prognostic Score, Systemic Inflammatory Response Markers, and TNM Staging in a Cohort of Colorectal Neuroendocrine Tumor Patients.

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.

Predictive value of pretreatment circulating inflammatory response markers in the neoadjuvant treatment of breast cancer: meta-analysis.

Systemic inflammatory response markers have been found to have a prognostic role in several cancers, but their value in predicting the response to neoadjuvant chemotherapy in breast cancer is uncertain. A systematic review and meta-analysis of the literature was carried out to investigate this. A systematic search of electronic databases was conducted to identify studies that explored the predictive value of circulating systemic inflammatory response markers in patients with breast cancer before commencing neoadjuvant therapy. A meta-analysis was undertaken for each inflammatory marker where three or more studies reported pCR rates in relation to the inflammatory marker. Outcome data are reported as ORs and 95% confidence intervals. A total of 49 studies were included, of which 42 were suitable for meta-analysis. A lower pretreatment neutrophil-to-lymphocyte ratio was associated with an increased pCR rate (pooled OR 1.66 (95% c.i. 1.32 to 2.09); P < 0.001). A lower white cell count (OR 1.96 (95% c.i. 1.29 to 2.97); P = 0.002) and a lower monocyte count (OR 3.20 (95% c.i. 1.71 to 5.97); P < 0.001) were also associated with a pCR. A higher lymphocyte count was associated with an increased pCR rate (OR 0.44 (95% c.i. 0.30 to 0.64); P < 0.001). The present study found the pretreatment neutrophil-to-lymphocyte ratio, white cell count, lymphocyte count, and monocyte count of value in the prediction of a pCR in the neoadjuvant treatment of breast cancer. Further research is required to determine their value in specific breast cancer subtypes and to establish optimal cut-off values, before their adoption in clinical practice.

Role of Molecular Biomarkers in Endometriosis-Related Infertility: A Narrative Review of the Literature.

Endometriosis is a chronic benign inflammatory disease that affects womenof reproductive age. The clinical presentations of endometriosis include dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. There is awell-established association between endometriosis and infertility. Therefore, there is a need for an early diagnosis of endometriosis-related infertility. In this study, we aim to identify the role of biomarkers as predictive factors of the presence of the disease and its severity and their correlation with the pregnancy outcome. We performed an electronic database search of all published studies in PubMed and EMBASE from January 2018 to May 2023. Numerous innovative biomarkers identified in cases of endometriosis and infertility have been studied over the past years, including micro-RNAs, BCL6 endometrial expression, cytotoxic T-lymphocyte antigen 4, human leukocyte antigen G, programmed cell death protein 1, programmed cell death ligand 1 immune checkpoint molecules, plasma fibronectin-fibrin complexes, homeobox A10 gene, systemic inflammatory response markers, uterine natural killer cells, and the eutopic endometrium proteome. Considerable research has been done to identify diagnostic biomarkers for the early detection and prevention of endometriosis-associated infertility. However, none of these biomarkers displayed enough diagnostic accuracy to be used in daily clinical practice. Future research is valuable to establish them as reliable diagnostic tools.

The Role of Leu-Enkephalin Synthetic Analogue in Regulation of Systemic Inflammatory Response and Prevention of ARDS in Severe Combined Injury

The aim of the study. To study the effect of ley-enkephalin synthetic analogue on the dynamics of inflammatory response markers and organ dysfunction in patients with severe combined trauma.Materials and methods. A prospective clinical study with historical control from two clinical centers — N. I. Pirogov State Clinical Hospital No. 1 and N.V. Sklifosovsky Clinical and Research Institute for Emergency Medicine — included men and women with severe combined trauma and the ISS scores values of 18–44, aged 18 to 70 years. Diagnostic and therapeutic approaches in all patients followed current international, national&amp; local protocols and 2022 clinical recommendations of the Russian Society of Surgeons «Combined and multiple trauma in combination with shock (Polytrauma)». In the study group, treatment was supplemented with extended (72 hours from the admission) infusion of the test drug through a syringe dispenser following the study protocol. Effects of the test drug prolonged infusion were evaluated for the following laboratory parameters: levels of cortisol, procalcitonin, interleukin 6, NTproBNP and leukocyte count. Laboratory tests were performed at 4 time points: prior to test drug infusion, 24 hours and 72 hours after initiation of infusion, and on Day 7. The study evaluated patient’s dynamics using APACHE II, SOFA and SAPS II scales and percentage of patients developing organ dysfunction (renal, respiratory, cardiovascular), rates of sepsis complications and mortality.Results. Patients who received the test drug had significantly lower concentrations of systemic inflammatory response markers, i. e. PCT (P=0.001) and IL-6 (P=0.010) after 24 hours of follow-up vs the control group patients. The incidence of ARDS has also decreased in the study group (P=0.011 vs control). Acute kidney injury (AKI) rate was insignificantly higher in the control group (P=0.349). The duration of hospital stay in the control group was 35 (17; 51) days vs 18 (14; 30) days in the study group (P=0.140)Conclusion. The use of ley-enkephalin synthetic analogue inhibits production of such key systemic inflammatory response markers as PCT and IL-6, and reduces PCT concentrations within 24 hours in patients with severe combined trauma. ARDS developed less frequently in the study group, but there was no significant difference in the incidence of AKI, AHF and infectious complications between the groups.

The value of lung function assessment and Testin expression detection in clinicopathological features and prognosis of NSCLC patients.

The aim of this study is to investigate the clinical value and potential prognostic significance of lung function assessment and Testin expression in non-small cell lung cancer (NSCLC) patients. The NSCLC patients were classified into three groups according to lung function: group of normal lung function, group of PRISm (preserved ratio impaired spirometry) (FEV1, forced expiratory volume during the first second < 80% predicted and FEV1/FVC (forced vital capacity) ≥ 70%) and group of COPD (chronic obstructive pulmonary disease) (FEV1/FVC < 70%). The pre-operational clinicopathological characteristics of these patients were recorded and the markers of systemic inflammatory response, including neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR) and eosinophils (EOS), were compared between three groups. The expression of Testin in NSCLC samples was detected by IHC and we further explored the correlation between Testin expression and clinicopathological characteristics and prognosis of NSCLC patients. Finally, Cox regression analysis was conducted to study the prognostic factors of NSCLC patients. Of the 158 NSCLC patients, percentages of normal lung function, PRISm and COPD were 41.4%, 22.8% and 36.1%, respectively. Patients with tumor in the left lung were more likely to have pulmonary dysfunction (PRISm and COPD) than the right lung. The markers of systemic inflammatory response showed differences to various degree in the three groups and NSCLC patients with PRISm or COPD presented more unfavorable prognosis than patients with normal function. The expression of Testin correlated with lymph node metastasis, TNM stage and tumor invasion of NSCLC patients. Moreover, patients with low Testin expression exhibited poorer disease-free survival and overall survival than those with high Testin expression. In Cox regression analysis, we found that PRISm, COPD and Testin expression served as prognostic factors in NSCLC patients. The presence of COPD or PRISm influenced systemic inflammatory response and prognosis of NSCLC patients. Testin expression correlated with clinicopathological features and could be potentially used as a prognostic marker in NSCLC.

Microenvironment, systemic inflammatory response and tumor markers considering consensus molecular subtypes of colorectal cancer.

Introduction: Colorectal carcinomas (CRC) are one of the most frequent malignancies worldwide. Based on gene expression profile analysis, CRCs can be classified into four distinct subtypes also known as the consensus molecular subtypes (CMS), which predict biological behaviour. Besides CMS, several other aspects of tumor microenvironment (TME) and systemic inflammatory response (SIR) influence the outcome of CRC patients. TME and inflammation have important role in the immune (CMS1) and mesenchymal (CMS4) subtypes, however, the relationship between these and systemic inflammation has not been assessed yet. Our objective was to evaluate the connection between CMS, TME and SIR, and to analyze the correlation between these markers and routinely used tumor markers, such as CEA (Carcinoembryonic Antigen) and CA19-9 (Carbohydrate Antigen 19-9). Methods: FFPE (Formalin Fixed Paraffin Embedded) samples of 185 CRC patients were collected. TME was described using tumor-stroma ratio (TSR), Klintrup-Makinen (KM) grade, and Glasgow Microenvironment Score (GMS). CMS classification was performed on tissue microarray using MLH1, PMS2, MSH2 and MSH6, and pan-cytokeratin, CDX2, FRMD6, HTR2B and ZEB1 immunohistochemical stains. Pre-operative tumor marker levels and inflammatory markers [C-reactive protein - CRP, albumin, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute platelet count (APC)] and patient history were retrieved using MedSolution database. Results: Amongst TME-markers, TSR correlated most consistently with adverse clinicopathological features (p < 0.001) and overall survival (p < 0.001). Elevated CRP and modified Glasgow Prognostic Score (mGPS) were associated with worse outcome and aggressive phenotype, similarly to tumor markers CEA and CA19-9. Stroma-Tumor Marker score (STM score), a new combined score of CA19-9 and TSR delivered the second best prognostication after mGPS. Furthermore, CMS4 showed association with TSR and several laboratory markers (albumin and platelet derived factors), but not with other SIR descriptors. CMS did not show any association with CEA and CA19-9 tumor markers. Conclusion: More routinely available TME, SIR and tumor markers alone and in combination deliver reliable prognostic data for choosing the patients with higher risk for propagation. CMS4 is linked with high TSR and poor prognosis, but in overall, CMS-classification showed only limited effect on SIR- and tumor-markers.

Application of mesenchymal stem cells in severe acute experimental pancreatitis

Background. The significance of the problem of acute pancreatitis is due to an increase in the incidence with an increase in the number of common forms of pancreatic necrosis, accompanied by a high incidence of severe complications.Aim. To determine the effect of regional application of mesenchymal stromal cells on the systemic manifestations of severe acute experimental pancreatitis.Material and methods. This experimental study was carried out on 42 adults Wistar rats. Acute pancreatitis was induced by administering 0.3 ml of 5% solution of non-ionic polyethylene glycol octylphenol ether detergent into the caudal part of the pancreas. The animals were randomly divided into 4 groups: Group I (n=6) consisting of intact animals, Group II (control group) (n=12) of rats with untreated pancreatitis, Group III (n=12) of rats with pancreatitis treated: anesthesia + infusions of 0.9% sodium chloride solution (saline), and Group IV (n=12) of rats with pancreatitis treated: anesthesia + infusions of saline + regional application of mesenchymal stromal cells. Animals were taken out of the experiment by euthanasia on the 3rd and 7th day. The hematological parameters, markers of systemic manifestation of the pathological process (pancreatic amylase, aspartate aminotransferase, alanine aminotransferase, urea, creatinine), markers of endogenous intoxication (lipid peroxidation activity, nitric oxide level), markers of systemic inflammatory response (C-reactive protein, tumour necrosis factor-alpha, interleukin-6) have been evaluated.Results. The application of mesenchymal stromal cells in the early stages of acute pancreatitis made a favourable effect on the platelet count, the level of glycemia, helped to reduce the content of endogenous intoxication elements (malonic dialdehyde, nitric oxide) and of those of the systemic inflammatory response (interleukin-6, tumor necrosis factor-α, C-reactive protein), which are key links in the pathogenesis of severe acute pancreatitis.Conclusion. Comparison of different treatment regimens for acute experimental pancreatitis has shown that the early use of mesenchymal stromal cells has a systemic positive effect and confirms the therapeutic efficacy of the method in the treatment of this disease.

O184: Predictive value of pre-treatment circulating inflammatory response markers in the neoadjuvant treatment of breast cancer: a systematic review and meta-analysis

Abstract Purpose Systemic inflammatory response markers have been found to have a prognostic role in several cancers, but their value in predicting response to neoadjuvant chemotherapy is uncertain. A systematic review and meta-analysis of the literature was carried out to investigate this. Methods A systematic search of electronic databases was conducted to identify studies that explored the predictive value of circulating systemic inflammatory response markers in patients with breast cancer prior to commencing neoadjuvant therapy. A meta-analysis was undertaken for each inflammatory marker where three or more studies reported pathological complete response (pCR) rates in relation to the inflammatory marker. Outcome data were reported as odds ratios (ORs) using 95% confidence intervals (CIs). Results Forty-nine studies were included in total, of which 42 were suitable for meta-analysis. Lower pre-treatment neutrophil-lymphocyte-ratio (NLR) was associated with an increased rate of pCR (pooled OR 1.66, 95% CI 1.32 to 2.09; P&amp;lt;0.001). Lower white cell count (WCC) (OR 1.96, 95% CI 1.29 to 2.97, P=0.002) and lower monocyte count (OR 3.20, 95% CI 1.71 to 5.97) were also associated with pCR. Higher lymphocyte count was associated with increased pCR rate (OR 0.44, 95% CI 0.30 to 0.64, P&amp;lt;0.0001). Conclusion The present study found pre-treatment NLR, WCC, lymphocyte count and monocyte count of value in the prediction of pCR in the neoadjuvant treatment of breast cancer. However, further research is required to determine their value in specific breast cancer subtypes and to establish optimal cut-off values, prior to their adoption in clinical practice.

Prognostic significance of the preoperative C-reactive protein-albumin-lymphocyte (CALLY) index on outcomes after gastrectomy for gastric cancer.

Systemic inflammatory response markers are reported to be prognostic for patients with cancer. The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index has been established as an immuno-nutritional scoring system. The aim of this study was to clarify the impact of the preoperative CALLY index on the outcome of patients undergoing gastrectomy for gastric cancer. We analyzed the data of 826 patients who underwent gastrectomy for stage I, II, or III gastric cancer between 2010 and 2017. The CALLY index was defined as (albumin × lymphocyte)/(CRP × 104). The cut-off of the CALLY index was 2. The 147 patients with a preoperative CALLY index < 2 had significantly worse overall survival (OS) and relapse-free survival (RFS) than those with a CALLY index ≥ 2 (P < 0.01, P < 0.01, respectively). Multivariate analysis identified that a CALLY index < 2 (P = 0.02), intraoperative blood loss (P < 0.01), and stage II or III disease (P < 0.01) were independent and significant predictors of worse RFS. A CALLY index < 2 (P = 0.01), intraoperative blood loss (P < 0.01), postoperative complications (P = 0.02), and stage II or III disease (P < 0.01) were independent and significant predictors of worse OS. The preoperative CALLY index was independently associated with a poor prognosis for patients after gastrectomy for gastric cancer.

Clinical and Laboratory Features and Maternal Outcomes in Pregnant Women with Critical Lung Damage in the COVID-19

Introduction. The spread of the delta strain of the SARS-CoV-2 virus during the third and fourth waves of the pandemic led to the fact that a large cohort of pregnant women and maternity women needed respiratory support, standard treatment methods had no effect, and negative outcomes for the mother and fetus has increased.Purpose of the study. The aim is to determine clinical and laboratory features and maternal outcomes in pregnant women with the coronavirus disease 2019 (COVID-19) and critical lung damage.Materials and methods. A comparative study was conducted, followed by a retrospective analysis of clinical and laboratory features, maternal outcomes in 56 pregnant women with COVID-19 treated in this maternity hospital in the first-fourth wave of the pandemic. The research method is continuous, sequential. The first group (main) consisted of 28 women with severe or extremely severe form of the course of COVID-19 and critical lung damage (more 75 %); The second group (comparison) — 28 pregnant women with a moderate form of the disease and lung damage of 25–50 %. Screening assessment of the degree of endogenous intoxication was carried out. The severity of the disease was determined by the evaluation scale National Early Warning Score (NEWS).Results. Laboratory parameters of patients at admission and at the height of the disease have statistically significant differences in the general blood test, such as higher levels of leukocytes, eosinophils, rod-shaped neutrophils, hemoglobin, as well as lymphopenia and monocytopenia in women of the main group at the height of the disease. At the same time, the hematological indices of intoxication in the main group exceed the value of these indicators in the comparison group by two times. Patients of both groups had high levels of acute-phase markers of inflammation — C-reactive protein and ferritin, — an indicator of tissue destruction of lactate dehydrogenase, however, both at admission and at the height of the disease, these indicators were statistically significantly higher in the group of women with critical lung damage. In general, 20/28 patients (71.4 %) of group 1 had an extremely severe course of the disease, 8/28 (28.6 %) had a severe course. In second group, 28/28 patients (100 %) had moderate-severe NCI (p = 0.000), while recovery was noted in all of them. Outcomes of COVID-19 in women with critical lung damage: recovered — 25/28 (89 %); 3/28 (10.7 %) the patients died from complications of COVID-19 of an extremely severe degree.Discussion. The most frequent laboratory anomaly was leukocytosis and a rod-shaped shift in the midst of the disease in women with critical lung damage, as well as a statistically significant increase in the level of C-reactive protein, lactate dehydrogenase, D-dimer. Pulmonary complications (parapneumonic pleurisy, pneumothorax, pneumomediastinum, hydrothorax, lung abscess) and extrapulmonary complications (encephalopathy, panic attacks, acute liver injury, sepsis, thromboembolic complications) were observed only with critical lung damage.Conclusion. In the laboratory, at the height of the disease, in the group of pregnant women with critical lung damage, leukocytosis and stab shift are statistically significantly more common. Hematological indices of intoxication, leukocyte and hematological, confirm endogenous intoxication at the height of the disease. A statistically significantly higher level of aspartate aminotransferase, lactate dehydrogenase, C-reactive protein, D-dimer is determined upon admission to the hospital and at the height of the disease as markers of systemic inflammatory response and cytolysis, which demonstrates the defeat of several organ systems simultaneously.

Prognostic significances of systemic inflammatory response markers in patients with synchronous esophageal and head and neck cancers.

Patients with head and neck squamous cell carcinoma (HNSCC) frequently develop synchronous esophageal cancer (ESCC), but there is a lack of clinical predictors. The neutrophil to lymphocyte (NLR), platelet to lymphocyte (PLR), and lymphocyte to monocyte ratios (LMRs), reflect the balance between pro-cancer inflammation and anti-cancer immune responses, but their role in HNSCC and synchronous cancer remain uncertain. The study consecutively enrolled a total of 717 patients with newly diagnosed HNSCC who received pre-treatment esophageal endoscopic screening. The pretreatment NLR, LMR and PLRs were calculated and analyzed in comparison with the clinical factors. A total of 103 patients (14.4%) were found to have synchronous ESCCs, and were associated with a significantly lower absolute lymphocyte count (p < 0.001), higher NLRs (p = 0.044) and lower LMRs (p = 0.001), but not PLRs (p = 0.49). The ROC curve for the presence of synchronous ESCC verified the optimal cutoff value as 2.5 for NLRs and 4.0 for LMRs. Multivariable logistic regression revealed that a LMR <4 (OR 2.22; 95% CI 1.27-3.88, p = 0.005), alcohol consumption (OR 4.19; 95% CI 1.47-11.91, p = 0.007), tumor location over the pharynx (OR 1.68; 95% CI 1.07-2.64, p = 0.025), and low body mass index (OR 0.94; 95% CI 0.88-0.99, p = 0.039) were risk factors for developing synchronous ESCC. A low-LMR was significantly associated with decreases in overall survival (p < 0.0001), in both synchronous and non-synchronous groups. Multivariate analysis demonstrated that LMR <4 (HR 1.97; 95% CI 1.38-2.81, p < 0.001), a low-BMI (HR 0.96; 95% CI 0.93-0.99, p = 0.044) and presence of synchronous ESCC (HR 1.56; 95% CI 1.10-2.22, p = 0.013) were independent prognostic factors for HNSCC patients. Incorporation of LMR into other identified risk factors, such as alcohol consumption, tumor location over pharynx, and low-BMI, may establish a more efficient screening program for esophageal exploration in HNSCC patients. The significances of LMR also suggest that anti-cancer immunity may play a role in the filed cancerization to initiate multiple cancers, and the immunotherapy may have potentials for prevention or as an adjuvant treatment for synchronous SCC in the future.

Comparison of platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios with epithelial ovarian cancer stages

Objectives: Epithelial ovarian cancer (EOC) is the most common histologic type among ovarian cancers. It is usually diagnosed at an advanced stage and the prognosis worsens. The aim of our study was to investigate the predictive value of serum platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), which are systemic inflammatory response markers in EOC stages. Methods: In this study, 140 patients diagnosed with primary EOC in İzmir Katip Çelebi University Atatürk Training and Research Hospital Gynecology and Obstetrics Clinic between 01.01.2012-01.07.2019 were included. The cases were staged using the FIGO 2014 Ovarian Cancer Staging system. Whether the PLR and NLR values were different between the stages were analyzed with appropriate statistical analysis methods. Results: A total of 140 patients, 54 were in the early stage (Stage I: 47; Stage II: 7) and 86 were in the advanced stage (Stage III: 73; Stage IV: 13). The PLR and NLR values differed between the four stages (p = 0.003 and p = 0.032, respectively). The PLR value was different between the early and advanced stages (p = 0.033), the AUC value was 0.607, the optimum cut-off was 220, the sensitivity was 47%, and the specificity was 81% in the early and advanced stage discrimination. Accordingly, the Odds ratio of PLR for advanced EOC was 3.82 (95% CI: 1.70-8.57, p = 0.0011). Conclusions: The NLR and PLR values were found to have a prognostic value in the discrimination of EOC stages. It has been determined that PLR value may play a predictive role in advanced EOC before surgery.

Systemic Inflammatory Response Following Preoperative Chemoradiotherapy Can Affect Oncologic Outcomes in MSI-H/dMMR Rectal Cancer.

Systemic inflammatory response (SIR) is a crucial determinant of disease progression and survival in patients with colorectal cancer. This study investigated the prognostic relevance of changes in the platelet count on survival and the predictive value of changes in the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) on the pathological tumor response to preoperative chemoradiotherapy (CRT) in patients with microsatellite instability-high (MSI-H) rectal cancer. From 2011 to 2022, data of 46 consecutive patients with MSI-H rectal cancer who were treated with preoperative CRT followed by curative surgery at Kyungpook National University Chilgok Hospital (Daegu, South Korea) were retrospectively analyzed. A 235 cut-off value was used to define whether PLR was high or low. Any change in the PLR or NLR was calculated on the basis of subtracting the pre-CRT PLR or NLR from the post-CRT values. Both pre-CRT and post-CRT values of the NLR and PLR were not significantly associated with clinical outcomes. Simple logistic regression analysis showed that a change in the PLR following CRT was not significantly associated with survival outcomes; however, patients who maintained a high change in the PLR following CRT showed significantly better pathologic T-stage. No statistically significant association was noted between changes in the platelet count and clinical outcomes of patients. The results suggested that changes in the PLR following CRT are associated with pathologic T-stage of the group. However, the SIR markers showed no prognostic values on the survival outcomes of the patients with MSI-H/mismatch repair-deficient (dMMR) locally advanced rectal cancer (LARC).

The diagnostic value of systemic inflammatory response markers as predictors of epithelial ovarian cancer

Background: Early detection of ovarian neoplasms confers a better outcome and prognosis for patients. Although newer diagnostic modalities have been recently developed, the availability and accessibility of complete blood count parameters make it a convenient and cost-effective marker for malignancy. Objectives were to evaluate the diagnostic accuracy of pretreatment neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in patients with late-stage epithelial ovarian malignancy at the University of Port Harcourt Teaching Hospital. Methods: A prospective analysis of fifty-seven women with histologic diagnosis of epithelial ovarian cancer who were managed at the University of Port Harcourt Teaching Hospital between January 1, 2018, and December 31, 2022, was conducted. A data collection form was used to obtain socio-demographic and clinico-pathological characteristics from the patients after informed consent was obtained. Pretreatment levels of NLR and PLR were determined from complete blood count. The Receiver Operating Characteristic (ROC) curve analysis was used to assess the predictive accuracy of the haematological parameters for late-stage epithelial ovarian cancer. Results: Higher values of NLR and PLR were significantly associated with the stage of ovarian cancer (p=0.001). The optimal cut-off points based on ROC curve analyses for NLR and PLR were found to be 2.6 (AUC=0.61, p&gt;0.05), and 155.8 (AUC=0.62, p&gt;0.05) respectively. However, none of the haematological parameters could be used as predictive markers for advanced-stage ovarian cancer in this study. Conclusions: Pretreatment NLR and PLR cannot be used as a stand-alone predictor of advanced ovarian cancer, and should be correlated with other clinical, laboratory and radiologic parameters.

A Prospective Study on the Roles of the Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), and Platelet-to-Lymphocyte Ratio (PLR) in Patients with Locally Advanced Rectal Cancer.

Rectal cancer constitutes over one-third of all colorectal cancers (CRCs) and is one of the leading causes of cancer-related deaths in developed countries. In order to identify high-risk patients and better adjust therapies, new markers are needed. Systemic inflammatory response (SIR) markers such as LMR, NLR, and PLR have proven to be highly prognostic in many malignancies, including CRC; however, their roles in locally advanced rectal cancer (LARC) are conflicting and lack proper validation. Sixty well-selected patients with LARC treated at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, between August 2017 and December 2020 were prospectively enrolled in this study. The reproducibility of the pre-treatment levels of the SIR markers, their correlations with clinicopathological characteristics, and their prognostic value were evaluated. There was a significant positive correlation between LMR and cancer-related inflammatory infiltrate (r = 0.38, p = 0.044) and PD-L1 expression in tumor cells, lymphocytes, and macrophages (combined positive score (CPS)) (r = 0.45, p = 0.016). The PLR level was correlated with nodal involvement (p = 0.033). The SIR markers proved to be only moderately reproducible and had no significant prognostic value. In conclusion, the LMR was associated with local cancer-related inflammation and PD-L1 expression in tumor microenvironments. The validity of SIR indices as biomarkers in LARC requires further investigation.

Systemic inflammatory response markers for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer

BackgroundTumour development is greatly influenced by the systemic inflammatory response. Inflammatory factors, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphcyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), mirror the balance between systemic inflammation and anti-tumour response. The current investigation examined the predictive and prognostic value of NLR, PLR, and LMR in advanced gastric cancer (GC) patients. MethodsThis study is a retrospective, observational analysis involving 105 GC patients treated with neoadjuvant chemotherapy (NAC). Thestudy population included patients who met the eligibility criteria.The relationship between NLR, PLR, LMR and demographic and clinical variables was assessed using theΧ2test. Survival data were analysed by Kaplan-Meier curves. ResultsHigh NLR levels were associated with more advanced tumour stage.Higher risk of no tumour regression after NAC was observed if a high pretreatment level of NLR or PLR was found. All patients with an increase in NLR after NAC had a significantly higher risk of no tumor response.In groups high (no change), increase, decrease, and low (no change), NLR and PLR OS medians were: 33, 67, 78, and not reached–NR and 34, 29, 36, and NR, respectively. All patients had a significantly higher risk of death if NLR increased after NAC. An increase in post-NAC PLR level was associated with an increased risk of death only if the PLR baseline value was low. ConclusionNLR and PLR are promising predictive and prognostic factors in advanced GC patients treated with NAC.

Minimal invasive extracorporeal circulation in comorbid patients

Background: As the severity of comorbid diseases increases, risks of cardiopulmonary bypass (CPB) complications significantly increase. A complex of the procedure’s damaging factors provokes a systemic inflammatory response that in some cases is accompanied by the damage to target organs, transitioning from chronic organ dysfunctions into acute ones. Some studies on the use of minimal invasive extracorporeal circulation (MiECC) systems show their advantage over conventional extracorporeal circulation (CECC); however, the diversity of MiECC systems, patients, and outcomes precludes us from confidently extrapolating these data to older comorbid patients.Objective: To compare the severity of systemic inflammation and treatment outcomes in comorbid patients who underwent cardiac surgery with CECC and MiECC.Methods: We conducted a retrospective cohort study of 760 patients who consecutively underwent elective cardiac operations in 2019-2022. Inclusion criteria: comorbid status (age-adjusted Charlson Comorbidity Index score of ≥6); CPB time ≥90 min. Exclusion criteria: emergency surgery, refusal to participate in the study. A total of 68 patients met the inclusion criteria. We formed 2 study groups based on the extracorporeal circulation method: CECC group (n = 51) and MiECC group (n = 17). Control points: before CPB and 24 hours after the surgery (lactate; creatinine; oxygenation index, hemolysis level). For systemic inflammatory response markers: 1 hour after the CPB start and 24 hours after the CPB end (interleukin 6; interleukin 10; procalcitonin; C-reactive protein; soluble Triggering Receptor Expressed on Myeloid Cells-1 [sTREM-1]). We evaluated respiratory and renal complications, drainage-related hemorrhages, hemostatic disorders, the need for sympathomimetic drugs, and the length of stay in an intensive care unit and inpatient hospital.Results: Between the groups there were no statistically significant differences in gender and anthropometric characteristics, surgery types, and main perfusion parameters. In the CECC group, we observed significantly higher doses of vasoconstrictors (norepinephrine) as well as a decrease in urine output and lung injury and an increase in lactate and hemolysis. The systemic inflammatory response markers were also significantly higher.Conclusion: Compared with CECC, MiECC does not significantly affect the frequency of organ dysfunctions; however, it reduces the severity of the systemic inflammatory response and immune suppression that are trigger mechanisms for multiple organ dysfunction syndrome. It is particularly important for patients with chronic organ dysfunctions. A range of indications for MiECC systems should be defined given its high cost and off-target effect on pleiotropic factors of systemic inflammatory response development. Received 6 April 2023. Revised 17 August 2023. Accepted 18 August 2023. Funding: The study was conducted within the framework of the research project "Development of minimally invasive and hybrid technologies for surgical treatment of heart diseases". Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: A.Sh. Revishvili, G.P. Plotnikov, V.A. PopovData collection and analysis: R.A. Kornelyuk, L.B. Berikashvili, I.P. Komkov, E.S. Malyshenko, V.M. ZemskovStatistical analysis: L.B. BerikashviliDrafting the article: R.A. Kornelyuk, G.P. Plotnikov, L.B. Berikashvili Critical revision of the article: G.P. PlotnikovFinal approval of the version to be published: A.Sh. Revishvili, R.A. Kornelyuk, G.P. Plotnikov, L.B. Berikashvili, I.P. Komkov, E.S. Malyshenko, V.M. Zemskov, V.A. Popov

Phases of systemic inflammation in septic and haemorrhagic shocks

Shocks of different origin (both septic and aseptic) be be considered clinical equivalents of systemic inflammation (SI) with following main manifestations : pronounced hypercytokinemia, other markers of systemic inflammatory response (SIR), coagulopathy, multiple organ failure (MOF), hypothalamic-pituitary-adrenal (HPA) distress, systemic tissue alteration. In general, these phenomena are directly and inversely related to systemic microcirculatory disturbances which determine the pathogenesis of distinct shock states. The aim of our study was to identify the features of SI phases in the development of two variants of septic shock, i.e., acute course (first week of the process) and prolonged/subacute sepsis (2 to 6 weeks from the onset of manifestations), as well as haemorrhagic shock studied 4-12 hours from the onset of massive blood loss. To verify the SI phases, we used the previously proposed SI scale, including the value of six SIR levels (RL-0-5), as well as additional criteria of SI, i.e., evaluation of clinical MOF grade (SOFA scale), plasma D-dimers ( 500 ng/mL), cortisol ( 1380 nmol/mL), tissue alteration markers, e.g., myoglobin ( 800 ng/mL) and/or troponin I ( 0.2 ng/mL). To calculate RL in SIR, plasma CRP and four cytokines (IL-6, IL-8, IL-10, TNF) were determined. The presence of SI was established if the SI scale exceeded 5 points (numerical RL values + presence of additional criteria, each equal to 1 point). The time and severity of the developing critical state, as well as the RL scores, were taken into account when reviewing the phases.&#x0D; There were three main SI phases: (1) evolving condition, (2) cytokine storm/phlogogenic hit (SD-4-5), and depressive (exhausting) phase. The latter was characterized by relatively low SIR values (RL-2-3). The lethality rate for shock in the presence of acute sepsis (n = 13) was 71.4%, reaching 94.1% in prolonged sepsis (n = 17). For haemorrhagic shock after massive blood loss, if not resolved within 24 hoursm the mortality rates was 53.8% (n = 13). Development of shock in acute sepsis, and haemorrhagic shock (within 4 to 12 hours after the onset of massive blood loss) is accompanied by the severity of critical-phase cytokine storm/PPS with a predominance of RL-5 in cases of lethal outcomes, and by a depression phase (RL-2-3) in prolonged sepsis. Overall mortality (for all groups) was 66.7% in the PS phase, 89.5% in the depressive phase and 15.4% in the evolvingl phase of haemorrhagic shock (with possible transition from this phase to the more critical SI phases until lethal outcome).&#x0D; Shock states of both septic and aseptic origin are based on a typical pathological process of SI, which should be distinguished from the signs of SIR characteristic of high-intensity canonical inflammation. It is characterized by higher cytokinemia (cytokine storm phase) or by the presence of additional SI phenomena with relatively moderate SIR levels (depressive SI phase). Thus, the depressive phase of SI is more fatal for disease outcome compared to the cytokine storm phase with higher intensity of SIR.