Elevated Systemic Inflammatory Response Research Articles

Anemia From Inflammation After Intracerebral Hemorrhage and Relationships With Outcome.

Baseline anemia is associated with poor intracerebral hemorrhage (ICH) outcomes. However, underlying drivers for anemia and whether anemia development after ICH impacts clinical outcomes are unknown. We hypothesized that inflammation drives anemia development after ICH and assessed their relationship to outcomes. Patients with serial hemoglobin and iron biomarker concentrations from the HIDEF (High-Dose Deferoxamine in Intracerebral Hemorrhage) trial were analyzed. Adjusted linear mixed models assessed laboratory changes over time. Of 42 patients, significant decrements in hemoglobin occurred with anemia increasing from 19% to 45% by day 5. Anemia of inflammation iron biomarker criteria was met in 88%. A separate cohort of 521 patients with ICH with more granular serial hemoglobin and long-term neurological outcome data was also investigated. Separate regression models assessed whether (1) systemic inflammatory response syndrome (SIRS) scores related to hemoglobin changes over time and (2) hemoglobin changes related to poor 90-day outcome. In this cohort, anemia prevalence increased from 30% to 71% within 2 days of admission yet persisted beyond this time. Elevated systemic inflammatory response syndrome was associated with greater hemoglobin decrements over time (adjusted parameter estimate: -0.27 [95% CI, -0.37 to -0.17]) and greater hemoglobin decrements were associated with poor outcomes (adjusted odds ratio per 1 g/dL increase, 0.76 [95% CI, 0.62-0.93]) independent to inflammation and ICH severity. We identified novel findings that acute anemia development after ICH is common, rapid, and related to inflammation. Because anemia development is associated with poor outcomes, further work is required to clarify if anemia, or its underlying drivers, are modifiable treatment targets that can improve ICH outcomes. https://www.clinicaltrials.gov Unique identifier: NCT01662895.

Phosphate Overload Stimulates Inflammatory Reaction via PiT-1 and Induces Vascular Calcification in Uremia

Vascular calcification (VC) is an important risk factor for cardiovascular disease in maintenance hemodialysis (MHD) patients. Hyperphosphatemia and microinflammation statement are known major contributors to the development of VC; however, the mechanisms are unknown. The aims of this study were to explore the risk factors of VC in MHD patients and to explore whether high phosphate could increase the secretion of inflammatory cytokines via PiT-1 in monocytes. A cross-sectional study was conducted on 65 MHD patients to assess the relevance of coronary artery calcification (CAC), inflammatory factors, serum phosphate, and sodium-dependent phosphate cotransporter (NPT) mRNA expression of peripheral blood mononuclear cells (PBMCs). Multivariate logistic regression analysis was used to analyze the predictors of CAC. The calcification effects of high phosphate (HP), TNF-α, and supernatants of healthy human monocytes treated with HP were further evaluated in cultured HASMCs. Diabetes, longer dialysis vintage, higher serum TNF-α levels, and PiT-1 mRNA expression of PBMCs) were independent risk factors of CAC in MHD patients. The mRNA levels of PiT-1 in PBMCs were positively correlated with serum phosphate, CAC scores, and Pit-2 mRNA levels of PBMCs. The expressions of TNF-α, IL-6, and PiT-1 in human monocytes were significantly increased in a dose-dependent manner after treatment with HP, which was subsequently inhibited by NPT antagonist phosphonoformic acid. Neither TNF-α alone nor supernatants of monocytes stimulated with HP promoted the expression of osteopontin and Runt-related transcription factor 2 (Runx2) or caused mineralization in human aortic smooth muscle cells, but combined with HP intervention, the calcification effects were markedly increased in human aortic smooth muscle cells and ameliorated by phosphonoformic acid treatment. Hyperphosphatemia directly increased the synthesis and secretion of TNF-α by monocytes may via PiT-1 pathway, resulting in elevated systemic inflammatory response, which may further aggravate VC induced by phosphate overload in MHD patients.

Elevated Systemic and Intestinal Inflammatory Response Are Associated With Gut Microbiome Disorder After Cardiovascular Surgery.

Systemic inflammatory response after cardiovascular surgery is associated with poor prognosis, to which gut barrier impairment is related. To investigate whether perioperative changes of the gut microbiome are associated with systemic and intestinal inflammatory response, we examined changes of the gut microbiome, intestinal homeostasis, and systemic inflammatory response in cardiovascular patients before (Pre) surgery and on the first defecation day [postoperative time 1 (Po1)] or a week [postoperative time 2 (Po2)] postsurgery. Markedly, the enhanced systemic inflammatory response was observed in Po1 and Po2 compared with that in Pre. In line with inflammatory response, impaired gut barrier and elevated gut local inflammation were observed in Po1 and Po2. Microbiome analysis showed a remarkable and steady decline of alpha diversity perioperatively. In addition, microbial composition in the postoperation period was characterized by significant expansion of Enterococcus along with a decrease in anaerobes (Blautia, Faecalibacterium, Bifidobacterium, Roseburia, Gemmiger, [Ruminococcus], and Coprococcus), which were typically health-associated bacteria. Spearman correlation analysis showed microbiome disorder was associated with enhanced systemic inflammatory response and intestinal dysbiosis. These results suggest that microbiome disorder was related to disturbed gut homeostatic and subsequently elevates plasma endotoxin and systemic inflammatory response after cardiovascular surgery. This study not only highlights gut microbiome would be considered in future clinical practice but also proposes a promising perspective of potential diagnostic and therapeutic options for perioperative management of cardiovascular surgery patients.

Gender differences in immunological response of African-American juveniles with Grade C molar incisor pattern periodontitis.

Prevalence of Grade C molar incisor periodontitis (C/MIP) in females (F) and males (M) is controversial, although some studies suggest higher prevalence in females. The objective of this study was to evaluate differences in clinical parameters, and levels of cyto/chemokines in gingival crevicular fluid (GCF) and peripheral blood response. GCF and blood were collected from 79 C/MIP African-American participants (53F and 26M) and healthy controls (58F and 38M), aged 5 to 23. Blood was stimulated with ultrapure LPS from Escherichia coli (Ec) and Porphyromonas gingivalis (Pg) and we quantified levels of 14 cyto/chemokines. Clinical parameters were collected before and 12 months following treatment RESULTS: No clinical parameters or age differences were found between males and females, although age was negatively correlated with response to treatment. GCF levels of TNFα, IFNγ, MIP1α, and MCP1 from diseased and sites and healthy sites IFNγ levels were higher in M (P<0.05). C/MIP females presented higher Pg and Ec LPS induced levels of Eotaxin, IFNγ, and GMCSF (P<0.05), whereas healthy males presented higher Ec LPS induced levels of Eotaxin and IFNγ (P<0.05). Inflammatory profiles were also different among genders in disease (P=0.004). Although males seemed to present few elevated inflammatory markers in the GCF in disease and in health, females presented an elevated systemic inflammatory response to LPS in disease, which indicates a possible differential susceptibility to inflammation. Future studies need to determine if sex hormones have a role in the peripheral host response and in the pathogenesis of C/MIP.

Elevated preoperative neutrophil\u2010to\u2010lymphocyte ratio predicts early adverse outcomes in uncomplicated type B aortic dissection undergoing TEVAR

BackgroundThoracic aortic endovascular repair (TEVAR) of uncomplicated type B aortic dissection (uTBAD) has favorable long-term outcomes but higher early adverse events compared with the optimal medical treatment. Recently, clinical evidence concerning vascular surgery indicates that elevated preoperative systemic inflammatory response predicts adverse clinical events. The aim of our study was to evaluate the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR) and early outcomes of uTBAD patients undergoing TEVAR.Results216 patients diagnosed with uTBAD were included in this retrospective study between January 2015 and December 2018. The median (IQR) follow-up period was 21 (15–33) months. An early adverse event was defined as occurring within 2 years after the procedure. Median patient age was 60 (IQR, 48–68) years and 78.7 % were male. Early adverse events occurred in 24 patients (11.1 %). In the multivariable analysis, preoperative NLR (HR per SD, 1.98; 95 % CI, 1.14–3.44; P = 0.015) was associated with 2-year adverse events.ConclusionsNLR is an independent predictive factor of early adverse events in uTBAD patients undergoing TEVAR.

Elevated systemic inflammatory responses, factors associated with physical and mental quality of life, and prognosis of hepatocellular carcinoma.

Impaired quality of life (QOL) is common in hepatocellular carcinoma (HCC) patients. In this study, we used a large hospital-based multiethnic HCC patient cohort to systematically identify factors associated with QOL and investigate the prognostic value of QOL.The Short Form-12 questionnaire was used to assess QOL. The Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were categorized into three groups (low, medium, and high) and ordered logistic regression analysis was used to analyze the association of PCS and MCS scores with patient characteristics. The association of PCS and MCS scores with mortality was assessed by Cox regression analysis.Notably, a panel of elevated systemic inflammatory response markers was associated with poor QOL. Other significant factors associated with QOL included age, liver function, sex, smoking, HCC etiology, and major clinical features. Patients with low (hazard ratio [95% CI], 1.72 [1.36-2.17]) and medium (1.52 [1.23-1.89]) PCS scores exhibited higher risks of death compared to patients with high PCS score. The association of MCS with the risk of death was not significant. These observations were consistent across all the different ethnicities.The identified factors associated with QOL may help clinicians formulate interventions to improve QOL and outcomes in HCC patients.

Systemic inflammation, adjuvant chemotherapy, and survival in stage III colorectal cancer: Results from the ScotScan Colorectal Cancer Collaborative.

228 Background: The systemic inflammatory response (SIR) is a poor prognostic marker in patients with colorectal cancer (CRC), and predicts poor outcome following adjuvant chemotherapy. Whether this may be influenced by chemotherapy regime is not known. The present study examined the relationship between the pre-operative SIR, adjuvant therapy regime, and survival of patients with stage III CRC in the ScotScan cohort. Methods: Patients with stage III CRC in Scotland (1997-2015, n= 317) and Norway (2000-17, n= 312) were included. The pre-operative SIR was measured using C-reactive protein (CRP≤10mg/L or &gt; 10mg/L). Adjuvant status was categorised as none, 5-fluorouracil-only (5FU or capecitabine), or oxaliplatin-combination (Ox). Relationship with 3 year overall (OS) and cancer-specific survival (CSS) was examined. Results: Rates of Ox were comparable between cohorts (Scotland – 26% vs. Norway 28%), although more patients from Norway received single 5FU (4% vs. 19%, P= 0.005). 36% of each cohort were systemically inflamed. Ox was associated with superior OS (90%) and CSS (92%) when compared to 5FU (77% and 84%) and no therapy (61% and 72%, both P&lt; 0.001). Stratified by SIR, patients with CRP≤10mg/L receiving Ox or 5FU had comparable 3yr OS greater than those receiving none (90% vs. 88% vs. 67%), whereas those with CRP &gt; 10mg/L receiving Ox had superior survival than those receiving 5FU or no therapy (89% vs. 64% vs. 53%, P-for interaction = 0.101). Results were similar for CSS (CRP≤10mg/L: 91% vs. 94% vs. 79%; CRP &gt; 10mg/L: 94% vs. 72% vs. 62%, P-for interaction= 0.01). Although patients receiving Ox were younger and less comorbid, both use of Ox and SIR remained independently associated with OS and CSS. Conclusions: Although selection bias in the choice of adjuvant therapy may confound analysis, this study suggests the SIR may aid in determining response to adjuvant therapy. Whereas non-inflamed patients with stage III CRC may benefit from single 5FU, those with an elevated SIR may benefit greater from more intensive, Ox-based regimes. These results remain to be validated, however support the use of the SIR as a prognostic and predictive biomarker in patients with stage III CRC.

Increased serum levels of high mobility group protein B1 and calprotectin in pre-eclampsia.

To determine whether women with pre-eclampsia have serum levels of biomarkers indicative of an elevated systemic inflammatory response. The present cross-sectional study was conducted among pregnant women either with pre-eclampsia or without pre-eclampsia who were recruited at a single Chinese hospital between August 1, 2016, and April 30, 2017. Eligible women had no history of acute or chronic inflammation. Serum concentrations of high mobility group protein B1 (HMG-1), calprotectin, and Toll-like receptor 4 (TLR4) were measured and compared. There were 55 patients included (25 with pre-eclampsia and 30 without). The mean serum concentration of calprotectin was 2656.76±1724.56μg/L in the pre-eclampsia group versus 1877.33±905.69μg/L in the control group (P=0.036). Among patients with pre-eclampsia, elevated calprotectin levels were positively associated with the duration of hypertension in pregnancy (P=0.031) and were negatively associated with pregnancy duration at delivery (P=0.035). The mean serum concentration of HMG-1 was 72.48±27.57μg/L in the pre-eclampsia group versus 57.57±20.07μg/L in the control group (P=0.017). The mean serum concentration of TLR4 was 22.83±8.46μg/L in the pre-eclampsia group versus 18.83±6.79μg/L in the control group (P=0.057). Elevated levels of HMG-1 and calprotectin could reflect an excessive systemic inflammatory response in pre-eclampsia.

Determinants of lymph node count and positivity in patients undergoing surgery for colon cancer.

Prognosis in colon cancer is based on pathological criteria including TNM staging. However, there are deficiencies in this approach, and the lymph node ratio (LNR) has been proposed to improve the prediction of outcomes. LNR is dependent on optimal retrieval of lymph nodes—lymph node count (LNC). Recent studies have suggested that an elevated preoperative systemic inflammatory response (SIR) was associated with a lower LNC and a higher LNR. However, there are a number of potential confounding factors. The aim of the present study was to examine, in detail, these relationships in a large cohort of patients.A prospectively maintained database of all patients undergoing colon cancer resection in our institution was examined. The SIR was measured by a number of inflammatory markers and their scores: modified Glasgow Prognostic Score (mGPS) (C-reactive protein/albumin), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and lymphocyte monocyte ratio (LMR) using standard thresholds. The relationships between LNC and LNR, and clinicopathological characteristics (including the mGPS, NLR, PLR, and LMR) were examined using chi-square test for trend and binary logistic regression analysis, where appropriate.Of the 896 patients included in the study, 418 (47%) were male, the median LNC was 17 (1–71), and the median LNR in node positive disease was 0.16 (0.03–1). On multivariate analysis, there was a significant independent relationship between an elevated LNC (≥12) and laparoscopic surgery (P < .001), right-sided tumors (P < .001), later date of resection (2007–2016) (P < .001), T stage (P < .001), and venous invasion (P < .001). In those patients with a LNC ≥12 and node-positive disease (n = 272), on multivariate analysis, there was a significant relationship between an elevated LNR (≥0.25), and T stage (P < .01) and differentiation (P < .05). Finally, in patients with node-positive disease who had surgery later (2007–2016), LNR was directly superior to N stage for both cancer-specific survival (LNR: hazard ratio [HR] 2.62, 95% confidence interval [CI] 1.25–5.52, P = .011) and overall survival (LNR: HR 2.02, 95% CI 1.12–3.68, P = .022).Neither LNC nor LNR was associated with markers of the SIR; however, LNC and LNR were directly associated. In high-quality surgical and pathological practice, LNR had superior prognostic value compared with N stage in patients undergoing surgery for colon cancer.

The relationship between right-sided tumour location, tumour microenvironment, systemic inflammation, adjuvant therapy and survival in patients undergoing surgery for colon and rectal cancer

Background:There has been an increasing interest in the role of tumour location in the treatment and prognosis of patients with colorectal cancer (CRC), specifically in the adjuvant setting. Together with genomic data, this has led to the proposal that right-sided and left-sided tumours should be considered as distinct biological and clinical entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), adjuvant chemotherapy and survival in patients undergoing potentially curative surgery for stage I–III colon and rectal cancer.Methods:Clinicopathological characteristics were extracted from a prospective database. MMR and BRAF status was determined using immunohistochemistry. The tumour microenvironment was assessed using routine H&E pathological sections. SIR was assessed using modified Glasgow Prognostic Score (mGPS), neutrophil:lymphocyte ratio (NLR), neutrophil:platelet score (NPS) and lymphocyte:monocyte ratio (LMR).Results:Overall, 972 patients were included. The majority were over 65 years (68%), male (55%), TNM stage II/III (82%). In all, 40% of patients had right-sided tumours and 31% had rectal cancers. Right-sided tumour location was associated with older age (P=0.001), deficient MMR (P=0.005), higher T stage (P<0.001), poor tumour differentiation (P<0.001), venous invasion (P=0.021), and high CD3+ within cancer cell nests (P=0.048). Right-sided location was consistently associated with a high SIR, mGPS (P<0.001) and NPS (P<0.001). There was no relationship between tumour location, adjuvant chemotherapy (P=0.632) or cancer-specific survival (CSS; P=0.377). In those 275 patients who received adjuvant chemotherapy, right-sided location was not associated with the MMR status (P=0.509) but was associated with higher T stage (P=0.001), venous invasion (P=0.036), CD3+ at the invasive margin (P=0.033) and CD3+ within cancer nests (P=0.012). There was no relationship between tumour location, SIR or CSS in the adjuvant group.Conclusions:Right-sided tumour location was associated with an elevated tumour lymphocytic infiltrate and an elevated SIR. There was no association between tumour location and survival in the non-adjuvant or adjuvant setting in patients undergoing potentially curative surgery for stage I–III colon and rectal cancer.

The role of the systemic inflammatory response in predicting outcomes in patients with operable cancer: Systematic review and meta-analysis

Cancer remains a leading causes of death worldwide and an elevated systemic inflammatory response (SIR) is associated with reduced survival in patients with operable cancer. This review aims to examine the evidence for the role of systemic inflammation based prognostic scores in patients with operable cancers. A wide-ranging literature review using targeted medical subject headings for human studies in English was carried out in the MEDLINE, EMBASE, and CDSR databases until the end of 2016. The SIR has independent prognostic value, across tumour types and geographical locations. In particular neutrophil lymphocyte ratio (NLR) (n = 158), platelet lymphocyte ratio (PLR) (n = 68), lymphocyte monocyte ratio (LMR) (n = 21) and Glasgow Prognostic Score/ modified Glasgow Prognostic Score (GPS/mGPS) (n = 60) were consistently validated. On meta-analysis there was a significant relationship between elevated NLR and overall survival (OS) (p < 0.00001)/ cancer specific survival (CSS) (p < 0.00001), between elevated LMR and OS (p < 0.00001)/CSS (p < 0.00001), and elevated PLR and OS (p < 0.00001)/CSS (p = 0.005). There was also a significant relationship between elevated GPS/mGPS and OS (p < 0.00001)/CSS (p < 0.00001). These results consolidate the prognostic value of the NLR, PLR, LMR and GPS/mGPS in patients with resectable cancers. This is particularly true for the NLR/GPS/mGPS which should form part of the routine preoperative and postoperative workup.

Clinicopathological Determinants of an Elevated Systemic Inflammatory Response Following Elective Potentially Curative Resection for Colorectal Cancer

IntroductionThe postoperative systemic inflammatory response (SIR) is related to both long- and short-term outcomes following surgery for colorectal cancer. However, it is not clear which clinicopathological factors are associated with the magnitude of the postoperative SIR. The present study was designed to determine the clinicopathological determinants of the postoperative systemic inflammatory response following colorectal cancer resection.MethodsPatients with a histologically proven diagnosis of colorectal cancer who underwent elective, potentially curative resection during a period from 1999 to 2013 were included in the study (n = 752). Clinicopathological data and the postoperative SIR, as evidenced by postoperative Glasgow Prognostic Score (poGPS), were recorded in a prospectively maintained database.ResultsThe majority of patients were aged 65 years or older, male, were overweight or obese, and had an open resection. After adjustment for year of operation, a high day 3 poGPS was independently associated with American Society of Anesthesiologists (ASA) grade (hazard ratio [HR] 1.96; confidence interval [CI] 1.25–3.09; p = 0.003), body mass index (BMI) (HR 1.60; CI 1.07–2.38; p = 0.001), mGPS (HR 2.03; CI 1.35–3.03; p = 0.001), and tumour site (HR 2.99; CI 1.56–5.71; p < 0.001). After adjustment for year of operation, a high day 4 poGPS was independently associated with ASA grade (HR 1.65; CI 1.06–2.57; p = 0.028), mGPS (HR 1.81; CI 1.22–2.68; p = 0.003), NLR (HR 0.50; CI 0.26–0.95; p = 0.034), and tumour site (HR 2.90; CI 1.49–5.65; p = 0.002).ConclusionsASA grade, BMI, mGPS, and tumour site were consistently associated with the magnitude of the postoperative systemic inflammatory response, evidenced by a high poGPS on days 3 and 4, in patients undergoing elective potentially curative resection for colorectal cancer.

Signal Transduction and Activator of Transcription-3 (STAT3) in Patients with Colorectal Cancer: Associations with the Phenotypic Features of the Tumor and Host.

Purpose: In patients with colorectal cancer, a high-density local inflammatory infiltrate response is associated with improved survival, whereas elevated systemic inflammatory responses are associated with poor survival. One potential unifying mechanism is the IL6/JAK/STAT3 pathway. The present study examines the relationship between tumor total STAT3 and phosphorylated STAT3Tyr705 (pSTAT3) expression, host inflammatory responses, and survival in patients undergoing resection of stage I-III colorectal cancer.Experimental Design: Immunohistochemical assessment of STAT3/pSTAT3 expression was performed using a tissue microarray and tumor cell expression divided into tertiles using the weighted histoscore. The relationship between STAT3/pSTAT3 expression and local inflammatory (CD3+, CD8+, CD45R0+, FOXP3+ T-cell density, and Klintrup-Mäkinen grade) and systemic inflammatory responses and cancer-specific survival were examined.Results: A total of 196 patients were included in the analysis. Cytoplasmic and nuclear STAT3 expression strongly correlated (r = 0.363; P < 0.001); nuclear STAT3 and pSTAT3 expression weakly correlated (r = 0.130; P = 0.068). Cytoplasmic STAT3 was inversely associated with the density of CD3+ (P = 0.012), CD8+ (P = 0.003), and FOXP3+ T lymphocytes (P = 0.002) within the cancer cell nests and was associated with an elevated systemic inflammatory response as measured by modified Glasgow Prognostic Score (mGPS2: 19% vs. 4%, P = 0.004).The combination of nuclear STAT3/pSTAT3 stratified 5-year survival from 81% to 62% (P = 0.012), however, was not associated with survival independent of venous invasion, tumor perforation, or tumor budding.Conclusions: In patients undergoing colorectal cancer resection, STAT3 expression was associated with adverse host inflammatory responses and reduced survival. Upregulation of tumor STAT3 may be an important mechanism whereby the tumor deregulates local and systemic inflammatory responses. Clin Cancer Res; 23(7); 1698-709. ©2016 AACR.

Editor's Choice

A comparison of tumour and host prognostic factors in screen-detected vs non screen-detected colorectal cancer: a contemporaneous study. Mansouri D, McMillan DC, McIlveen E, Crighton EM, Morrison DS, Horgan PG.1 Current guidelines generally recommend screening for colorectal cancer from the age of 50, as there is compelling evidence that the benefits outweigh the risks. Screening can either prevent cancer by early polyp removal or improve disease-specific survival due to detection of early tumours. As prognosis in colorectal cancer is directly related to stage, the beneficiary effect of screening is by no means a surprise. I have been wondering for a long time, however, whether improved survival is also related to a different biological entity of screen-detected (SD) tumours, with better prognosis than non-screen-detected (NSD) cancer. After all, it might be possible that we are (also) looking at the effect of length-time bias (i.e. artificially improved cancer outcome due to the identification of indolent slow growing tumours). The study in this issue by Mansouri et al. assesses for the first time both host-factors and tumour-phenotype, in addition to tumour stage and site, within the context of a colorectal cancer screening programme. Compared to NSD tumours (both non-responders to screening and patients with interval tumours), patients with SD tumours had less advanced T-stage and less evidence of venous invasion. They had also less evidence of an elevated preoperative systemic inflammatory response. When adjustment was made for stage, however, the two key features representing phenotypically more aggressive tumours (i.e. venous invasion and poor differentiation) did not achieve statistical significance. Subgroup analysis comparing SD tumours with (more aggressive) interval tumours also did not show difference in prognostic factors when adjusted for stage. The conclusion was therefore drawn that the inherent biological characteristics of SD tumours do not differ from those of NSD disease. I agree, although it should be realized that the present study represents a population setting where compliance to the screening programme was just over 50%, and only a minority of interval tumours was detected, which might have influenced the results. So, although slightly reassured, I am still hoping for more studies which address this fascinating subject.

Preoperative platelet/lymphocyte ratio is a superior prognostic factor compared to other systemic inflammatory response markers in ovarian cancer patients.

The aim of the present study was to determine the most meaningful preoperative prognostic factor of cancer-related death in ovarian cancer patients by comparing potentially prognostic systemic inflammatory response (SIR) markers. The levels of fibrinogen, albumin, C-reactive protein (CRP), and serum cancer antigen-125 (CA-125) and the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were evaluated in 190 ovarian cancer patients to identify predictors of overall survival (OS) and progression-free survival (PFS) using univariate and multivariate analyses. Patients with a PLR >203 had a shorter PFS and OS than the patients in PLR ≤203 group (11 vs. 24 months and 28 vs. 64 months). Univariate analyses revealed that tumor stage, postoperative residual tumor mass, ascites, and the levels of all SIR markers were associated with PFS and OS. Multivariate analysis revealed that PLR was independently associated with PFS (hazard ratio [HR] 1.852, 95% confidence interval [CI] 1.271-2.697, P = 0.001) and OS (HR 2.158, 95%CI 1.468-3.171, P < 0.001), as well as tumor stage and postoperative residual tumor mass. In contrast, fibrinogen remained significant only for PFS (HR 1.724, 95%CI 1.197-2.482, P = 0.003). Patients with a PLR >203 were more prone to have advanced tumor stage (P = 0.002), postoperative residual tumor mass >2 cm (P = 0.032), malignant ascites (P < 0.001), and all the other elevated SIR markers (P < 0.001). Preoperative PLR is superior to other SIR markers (CA-125, NLR, fibrinogen, CRP, and albumin) as a predictor of survival in ovarian cancer patients.

Systemic inflammatory response syndrome and platelet count ≥250×10(9) are associated with venous thromboembolic disease.

IntroductionPrior research has demonstrated that platelet count and inflammation are dominant contributors to hypercoagulability. Our objective is to determine whether elevated platelet count and systemic inflammatory response syndrome (SIRS) have an association with the development of venous thromboembolism (VTE) in hospitalized patients with a high clinical index of suspicion for thromboembolic disease.MethodsWe performed a retrospective medical record review of 844 medical and surgical patients with suspected VTE hospitalized from July 2012 to May 2013 who underwent screening by venous duplex and computed tomography pulmonary angiogram. For our purposes, thrombocytosis was arbitrarily defined as platelet count ≥250×109/L.ResultsVenous thromboembolic disease was detected in 229 patients (25.9%). Thrombocytosis was present in 389 patients (44%) and SIRS was present in 203 patients (23%) around the time of imaging. Thrombocytosis and SIRS were positively correlated with VTE (P<0.001). There was no correlation between thrombocytosis and SIRS. Multivariate analysis revealed that SIRS (odds ratio 1.91, 95% confidence interval 1.36–2.68, P<0.001) and thrombocytosis (odds ration 1.67, 95% confidence interval 1.23–2.26, P=0.001) were independently associated with VTE.ConclusionPatients at high risk for VTE should be routinely assessed for thrombocytosis (≥250×109/L) and SIRS; if either is present, consideration for empiric anticoagulation should be given while diagnostic imaging is undertaken.

Alziemer's Disease and Periodontal Disease Bidirectional Interrelationships

Alzheimer’s disease is the most common form of dementia. It is a brain disorder which gradually destroys the ability to reason, remember imagine and learn. Over the course of the disease people with alziemer disease no longer recognizes themselves or much about the world around them. Periodontal infections may result in harmful pathogenic products leading to systemic inflammatory responses. Elevated systemic inflammatory response may contribute to the exacerbation of existing brain pathologies. Infections may also contribute to vascular pathology with the potential to impact brain function.

The relationship between systemic inflammation-based prognostic scores and body composition analysis in colorectal cancer patients.

407 Background: Weight loss in cancer is increasingly recognised as part of syndrome associated with chronic activation of the systemic inflammatory response (McMillan DC, 2009). The aim of the present study was to examine the relationship between systemic inflammation based prognostic scores (SIBPS) and CT measured parameters of body composition in patients with primary operable colorectal cancer (CRC). Methods: 303 patients with primary operable CRC who underwent resection with curative intent (2003-2012) were studied. Image analysis of CT scans was used to measure total fat index (cm2/m2), subcutaneous fat index (cm2/m2), visceral fat index (cm2/m2) and skeletal muscle index (cm2/m2). SIBPS included the Glasgow Prognostic Score (mGPS), Neutrophil: Lymphocyte ratio (NLR), Platelet: Lymphocyte Ratio (PLR), Prognostic Index (PI), and Prognostic Nutritional Index (PNI). Results: In all patients there was a significant association between lower BMI and skeletal muscle index and an elevated systemic inflammatory response, as measured by the mGPS (p=0.028 and p&lt;0.001), NLR (p=0.004 and p=0.002), and PNI (p=0.001 and p=0.022). In male patients there was a significant association between lower BMI, total fat mass and skeletal muscle index and an elevated systemic inflammatory response, as measured by the mGPS (p= 0.027, p=0.048 and p=0.001), NLR (p=0.002, p=0.034 and p=0.003), and PNI (p=0.003, p&lt;0.001 and p0.048). In female patients total body fat was associated with the PLR (p=0.001) and PNI (p=0.009) but only the mGPS (p=0.007) and the PI (p=0.013) were associated with reduced skeletal muscle. Conclusions: The present study highlights a consistent association between lower BMI and skeletal muscle mass and the presence of a systemic inflammatory response. These results are consistent with the hypothesis that chronic activation of the systemic inflammatory response results in the loss of lean tissue and that ultimately compromises survival in patients with CRC. McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009;12:223-6.

The Relationships between Body Composition and the Systemic Inflammatory Response in Patients with Primary Operable Colorectal Cancer

BackgroundWeight loss is recognised as a marker of poor prognosis in patients with cancer but the aetiology of cancer cachexia remains unclear. The aim of the present study was to examine the relationships between CT measured parameters of body composition and the systemic inflammatory response in patients with primary operable colorectal cancer.Patient and Methods174 patients with primary operable colorectal cancer who underwent resection with curative intent (2003–2010). Image analysis of CT scans was used to measure total fat index (cm2/m2), subcutaneous fat index (cm2/m2), visceral fat index (cm2/m2) and skeletal muscle index (cm2/m2). Systemic inflammatory response was measured by serum white cell count (WCC), neutrophil:lymphocyte ratio (NLR) and the Glasgow Prognostic Score (mGPS).ResultsThere were no relationships between any parameter of body composition and serum WCC or NLR. There was a significant relationship between low skeletal muscle index and an elevated systemic inflammatory response, as measured by the mGPS (p = 0.001). This was confirmed by linear relationships between skeletal muscle index and both C-reactive protein (r = −0.21, p = 0.005) and albumin (r = 0.31, p<0.001). There was no association between skeletal muscle index and tumour stage.ConclusionsThe present study highlights a direct relationship between low levels of skeletal muscle and the presence of a systemic inflammatory response in patients with primary operable colorectal cancer.

Plasma calprotectin as inflammation marker in pregnancies complicated by diabetes mellitus and superimposed preeclampsia

Objective We hypothesized that pregnancies complicated by diabetes mellitus with or without preeclampsia show an elevated systemic inflammatory response evaluated by the inflammation markers calprotectin and high-sensitivity C-reactive protein (hsCRP). Study design Third trimester EDTA plasma and serum from 138 women with diabetes mellitus (type 1, n = 53; type 2, n = 11; gestational diabetes mellitus (GDM), n = 63; diabetes mellitus with preeclampsia, n = 11) were analyzed for calprotectin and hsCRP and compared to previously published results from 37 healthy and 27 preeclamptic pregnancies. Results Median plasma calprotectin concentration was intermediate in women with GDM as compared to healthy and preeclamptic pregnancies (729 vs 552 and 1081 μg/L, P = .006 and P = .001, respectively). In diabetic pregnancies with preeclampsia, median plasma calprotectin concentration was elevated as compared to controls, but not different from women with preeclampsia alone (969 vs 552 and 1081 μg/L, P = .01 and P = .1, respectively). hsCRP was only elevated in type 2 diabetic pregnancies as compared to healthy pregnancies (6.6 vs 3.8 mg/L, P =.02). Conclusion Elevated plasma calprotectin concentrations in GDM may reflect an accentuated inflammatory process, possibly contributing to the augmented preeclampsia risk. Increased plasma calprotectin in diabetic pregnancies with preeclampsia may originate from the excess systemic inflammatory response associated with preeclampsia.