Linking inflammation and thrombosis:Role of C-reactive protein

C-reactive protein(CRP) is a biomarker of inflammation.Increased plasma levels of CRP are associated with an increased risk of myocardial infarction.However,the correlation between plasma CRP concentration and atherosclerotic plaque burden is poor.Based on these observations,it has been hypothesized that CRP increases the risk of myocardial infarction by promoting thrombosis.This article reviews available data that link enhanced CRP expression to increased risk of thrombosis,with a focus on the effects of CRP on hemostasis,platelet function,and fibrinolysis.Overall,the available data support the hypothesis that CRP is an important mechanistic link between inflammation and throm bosis.

Correlation between carotid atherosclerosis and serum high-sensitivity C-reactive protein in patients with cerebral infarction

BACKGROUND： Some researches demonstrate that high-sensitivity C-reactive protein may be a risk factor to cause carotid atherosclerosis in patients with cerebral infarction. Inflammatory reaction may participate in formation of carotid atherosclerosis in patients with acute cerebral infarction. OBJECTIVE： To investigate the correlation between levels of serum high-sensitivity C-reactive protein and carotid atherosclerosis in patients with acute cerebral infarction accompanied with carotid atherosclerosis. DESIGN： Contrast observation between two groups. SETTING： Department of Neurology, Zhenzhou Hospital, Shenyang Medical College. PARTICIPANTS： A total of 102 patients with acute cerebral infarction regarded as cerebral infarction group were selected from Department of Neurology, Shenzhou Hospital Affiliated to Shenyang Medical College from February 2005 to September 2006. There were 55 males and 47 females and their ages ranged from 55 to 86 years. All patients met the variously diagnostic points of cerebral infarction established by the Fourth National Cerebrovascular Disease Academic Meeting and were finally diagnosed with CT or MRI examination. Illness course was in an acute phase. A total of 96 healthy subjects were regarded as control group, including 51 males and 45 females aged from 48 to 78 years. All accepted subjects provided the confirmed consent. METHODS： ① Patients in the cerebral infarction group received carotid ultrasound Doppler examination and serum high-sensitivity C-reactive protein detection within 72 hours after onset. IMMAGE immune biochemical system and latex reinforcement particle-enhanced nephelometric ilnmunoassay （PENIA） were used for quantitative detection of serum high-sensitivity C-reactive protein. ② Healthy subjects in the control group received the same detection. SEQUOIA512 color Doppler ultrasound （Siemens Company, USA） was used to detect carotid artery of all subjects so as to observe intima media thickness of artery and formation of artery atherosclerostic plaques. If artery atherosclerostic plaques were formed, their properties and amounts were determined based on the characteristics of light-echo signals. Evaluating criteria： Intima media thickness of artery was the vertical dimension from crossed face between lumen and tunica intima to crossed face between tunica media and tunica adventitia. Intima media thickness ≤ 0.9 into was regarded as normal; 0.9 inm 〈 intima media thickness ≤ 1.2 inm was regarded as thickening; when local eminence thickening was processed towards to lumen, the intima media thickness was more than 1.2 into and plaque of tunica intima was formed at the same time. Properties of plaque were classified into 4 types： steady low-echo lipid malacoplakia, equal-echo fiber plaque, strong-echo or sound-imaging calcification hard plaque and unsteady-echo ulcer mixed plaque. Fiber plaque and calcification hard plaque were steady but malacoplakia and mixed plaque were unsteady. MAIN OUTCOME MEASURES： Thickness of tunica media, characteristics of plaque and level of serum high-sensitivity C-reactive protein in carotid artery in two groups. RESULTS： All 102 patients with cerebral infarction and 96 healthy subjects were involved in the final analysis. ①Comparisons of level of high-sensitivity C-reactive protein： Level of high-sensitivity C-reactive protein in normal tunica media was higher in the cerebral infarction group [（4.66±1.55） mg/L] than the control group [（3.49±1.24） mg/L, t =2.541, P 〈 0.05]. In addition, level of high-sensitivity C-reactive protein in patients with thickening tunica media and plaque was not significantly different between the cerebral infarction group and the control group （P 〉 0.05）. ② Correlation between various degrees of vascular lesion and level of high-sensitivity C-reactive protein in the cerebral infarction group： Level of high-sensitivity C-reactive protein was statistically significantly higher in patients with thickening tunica media [（8.16±2.42） mg/L] than patients with normal tunica media [（4.66±1.55） mg/L, t =4.132, P 〈 0.01]. In addition, level of high-sensitivity C-reactive protein was statistically significantly higher in patients with carotid plaque [（12.08±3.85） mg/L] than patients with normal tunica media （t =5.994, P 〈 0.01） and thickening tunica media （t =4.197, P 〈 0.01）. ③ Levels of high-sensitivity C-reactive protein in patients with various kinds of carotid plaque： Level of high-sensitivity C-reactive protein was statistically significantly higher in patients with unsteady carotid plaque [（13.54±2.62） mg/L] than patients with steady carotid plaque [（8.61±3.71） mg/L, t =2.002, P 〈 0.05]. That was to say level of serum high-sensitivity C-reactive protein in patients who suffered acute cerebral infarction combined with carotid atherosclerosis especially carotid plaque was higher than that in those patients who did not have carotid lesions. This suggested that serum high-sensitivity C-reactive protein had a certain correlation with onset of carotid atherosclerosis in patients with acute cerebral infarction. CONCLUSION： Serum high-sensitivity C-reactive protein certainly correlates with onset of carotid atherosclerosis in patients with acute cerebral infarction, while inflammatory reaction may participate in formation of carotid atherosclerosis in patients with acute cerebral infarction.

Inflammation: Complexity and significance of cellular and molecular responses

Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.

Relationship of High Sensitivity C-Reactive Protein with Cardiovascular, Diabetic, and Hepatic Biomarkers

Biomarkers are early predictors of various disorders, circulating level of C-reactive protein is a sensitive biomarker of systemic inflammation and may also be associated with the development of diabetic, hepatic, and cardiovascular diseases. In the present study, we aimed to investigate the association between circulating levels of high sensitive C-reactive protein (hs-CRP) and various biomarkers for hepatic, diabetic, and cardiovascular health. The retrospective analysis included 438 individuals who were tested for these panels simultaneously at Vibrant America Clinical Laboratory. The study population included free-living individuals without any preexisting clinical conditions. Among the cardiovascular markers, a positive correlation and significant association was found between high levels of hs-CRP and serum levels of triglycerides (r = 0.0964, p −0.1423, p −0.1216, p < 0.0105) with circulating levels of hs-CRP. Among all the diabetic markers, glucose (r = 0.1547, p < 0.0011) and glycated serum protein (r = 0.1725, p < 0.0003) were positively correlated with circulating hs-CRP. In the hepatic panel, AST, a transaminase that plays a vital role in amino acid metabolism, was found to have a strong positive correlation with hs-CRP (r = 0.2139, p < 0.0001). In conclusion, the results clearly show the association of hs-CRP with diabetic, hepatic, and cardiovascular risk factors indicating its central value as a key marker for several lifestyle-associated disorders.

Elevated Homocysteine and C-reactive Protein Levels Independently Predict Worsening Prognosis after Stroke in Chinese Patients

Increased plasma total homocysteine (tHcy) and high sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular disease.However, the predictive value of tHcy in combination with hsCRP in patients with stroke is not known.To determine the relationship between tHcy and hsCRP, we enrolled 291 patients with first-onset stroke (196 ischemic and 95 hemorrhagic).Plasma tHcy and hsCRP levels were measured and subsequent vascular events and deaths were determined over a 5-year period.Using the arbitrary cutoff for tHcy (【18 μmol/L and ≥18 μmol/L) and hsCRP (【1 mg/L, 1-3 mg/L and 】3 mg/L), the patients were divided into 6 groups.Survival analysis showed that the probability of death or new vascular events during a 5-year follow-up increased according to tHcy and hsCRP levels (P【0.01).The relative risk (RR) of death or new vascular events was 4.67 (95% CI, 1.96 to 11.14, P=0.001) in patients with high tHcy (≥18 μmol/L) and hsCRP (】3 mg/L) compared with those with low tHcy (【18 μmol/L) and hsCRP (【1 mg/L).The increased tHcy level (≥18 μmol/L) combined with increased hsCRP level (】3 mg/L) was still significantly associated with the risk of death or new vascular events (RR, 4.10, 95% CI, 1.61 to 10.45, P=0.003) even when adjusted for other risk factors at inclusion.The combination of increased tHcy and hsCRP levels had a stronger predictive value than increased hsCRP alone or increased tHcy level alone.Further studies are required to evaluate the potential decrease in risks associated with lowering both Hcy and hsCRP levels in patients that present with both increased tHcy and hsCRP.

Establishment of Nasal Tolerance to Heat Shock Protein-60 Alleviates Atherosclerosis by Inducing TGF-β-dependent Regulatory T Cells

Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether nasal tolerance to antigen likewise induces the novel Tregs production and the relevant antiatherosclerotic benefit.We investigated the effect of nasal administration of heat shock protein-60 (HSP60) on atherogenesis.HSP60 or phosphate buffer solution (PBS) was nasally adminis-tered to six-week-old male ApoE-/-mice.At the 10th week after the nasal administration,there was a significant decrease in atherosclerotic plaque areas of aortic roots in the HSP60-treated mice as com-pared with those in the PBS-treated mice.Atherosclerosis suppression was accompanied with a signifi-cant increase in CD4+LAP+ and CD4+CD25+Foxp3+ Tregs and a concurrently increased production of TGF-β in the HSP60-treated mice.The protective effect of HSP60 was offset by injection of anti-TGF-βantibody.It is concluded that nasal administration of HSP60 can inhibit atherosclerotic formation through immune tolerance which is established by Tregs depending on the induction of anti-inflammatory cytokine TGF-β.Immune tolerance induced by nasal administration of HSP60 may provide an alternative therapeutic method for atherosclerosis.

C-reactive protein and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus

AIM：To investigate the relationship between Creactive protein（CRP）and diabetic retinopathy（DR）in a cohort of Chinese patients with type 2 diabetes mellitus（T2DM）.·METHODS：Community-based observational cohort study.There were 1131 participants recruited from November 2009 to September 2011 in Desheng community in urban Beijing.Patients diagnosed T2DM were recruited and underwent a standardized evaluation consisting of a questionnaire,ocular and anthropometric examinations and laboratory investigation.The presence and severity of DR were assessed by seven fields 30°color fundus photographs.Subjects were then classified into groups with no DR,any DR,or vision-threatening DR.CRP was analyzed from serum of study subjects.·RESULTS：A total of 1007 patients with T2DM were included for analysis,including 408（40.5%）men and 599（59.5%）women.The median CRP level was 1.5 mg/L for women and 1.1 mg/L for men（=0.004,OR 0.37,95%CI0.18-0.74）.After adjusting for possible covariates,higher levels of CRP were associated with lower prevalence of any DR（=0.02,OR 0.55,95%CI 0.35-0.89）,but not associated with vision-threatening DR（=0.62,OR 0.78,95%CI 0.28-2.14）.After stratification by sex,the inverse association between CRP and DR was found to be statistically significant in men（=0.006,OR 0.35,95%CI0.16-0.73）,but not in women（=0.58,OR 0.88,95%CI0.29-1.16）.·CONCLUSION：The data drawn from a Chinese population with T2DM suggest that increasing CRP levels may be inversely associated with development of DR.

Study on correlation between C-reactive protein and gestational diabetes mellitus

Objective：To investigate correlation between C-reactive protein（CRP） and gestational diabetes mellitus（GDM）, Methods：Twentyfive GDM women were served as study group, and thirty normal pregnant women were selected as control group. The serum FPG, 2hPG, HbAlc and CRP levels and the leukocyte count were detected in the two groups, in order to observe the relationship between gestational diabetes mellitus and inflammatory markers. Results：The age and gestational week did not show difference in the two groups（P〉 0.05）. But there was a significant difference in body mass index（BMI） between the GDM group and the controtgroup（P 〈 0.05）. The serum FPG, 2hPG, HbAlc and CRP levels and the leukocyte count in the GDM group were higher than those in the control group, and the difference was significant（P 〈 0.05）, There was positive correlation between serum C-reactive protein value and FPG, 2hPG, HbAlc serum levels or the leukocyte count in GDM group. But in the control group there was no correlation between them. Conclusion：The results suggest that there is correlation between C-reactive protein and gestational diabetes mellitus, and inflammation may play an important role in the development of gestational diabetes mellitus.

Distribution of High-sensitivity C-reactive Protein Status in an Urban Population in China

Objectives To evaluate the distribution by age and sex of serum high-sensitivity C-reactive protein(hsCRP)in an urban Chinese population and to provide a profile prediction for the risk of bacterial infection,inflammatory diseases,or tissue damages in the body.Methods Serum hsCRP was determined using the Roche Tina-quant immuno-turbidimetric assay on a Hitachi 7600–010 automatic biochemical analyzer(Roche Diagnostics)in 1,572 males and 1,800 females,including 78 pregnant women,who were derived from the National Health and Nutrition Survey in2010–2012.Results The average hsCRP concentration in urban China was 0.68 mg/L for males and 0.65 mg/L for females.Significant differences in hsCRP were found among different age groups(P<0.05).Monitoring results showed no significant differences among the 6–11,45–59,and≥60-year-old groups in the comparison of hsCRP between males and females in large cities.However,hsCRP concentration was significantly higher in men aged 12–17 and 18–44 years than in women.Conclusion The distribution of the hsCRP status of residents in large cities in China was influenced by age and gender,and the hsCRP levels of both sexes increased gradually with age.In addition,hsCRP concentration was higher in healthy pregnant women than in non-pregnant women.Basing on our results,we recommend that this parameter be included in future national and international screening for early detection of various illnesses.

Preoperative lymphocyte to C-reactive protein ratio as a new prognostic indicator in patients with resectable gallbladder cancer

Background:Inflammation is often related to cancer,and several inflammatory scores have been established to predict the prognosis of various types of cancer.Our study aimed to determine the prognostic value of the preoperative lymphocyte to C-reactive protein ratio(LCR)for predicting postoperative outcomes in patients with resectable gallbladder cancer(GBC).Methods:A retrospective analysis of 104 GBC patients who received curative surgery at Xinhua Hospital,Affiliated to Shanghai Jiao Tong University School of Medicine from January 2000 to December 2016 was performed.A time-dependent receiver operating characteristic curve was constructed to evaluate the accuracy of different markers.Univariate and multivariate Cox proportional hazard models were used to define factors associated with overall survival.Results:Among the assessed variables,the preoperative LCR showed the highest accuracy in predicting the overall survival of GBC patients(AUC:0.736).Decreased preoperative LCR was significantly associated with advanced tumor stage,including tumor invasion(P=0.018),lymph node metastasis(P=0.011)and TNM stage(P=0.022).A low preoperative LCR(cutoff threshold=145.5)was an independent risk factor for overall survival in patients with resectable GBC(P<0.001).Conclusions:The preoperative LCR is a novel and valuable prognostic indicator of postoperative survival in patients with resectable GBC.

Prospects and advancements in C-reactive protein detection

C-reactive protein(CRP) is one of the earliest proteins that appear in the blood circulation in most systemic inflammatory conditions and this is the reason for its significance,even after identification of many organ specific inflammatory markers which appear relatively late during the course of disease.Earlier methods of CRP detection were based on the classical methods of antigen-antibody interaction through precipitation and agglutination reactions.Later on,CRP based enzymatic assays came into the picture which were further modified by integration of an antigen-antibody detection system with surface plasma spectroscopy.Then came the time for the development of electrochemical biosensors where nanomaterials were used to make a highly sensitive and portable detection system based on silicon nanowire,metal-oxide-semiconductor field-effect transistor/bipolar junction transistor,ZnS nanoparticle,aptamer,field emission transmitter,vertical flow immunoassay etc.This editorial attempts to summarize developments in the field of CRP detection,with a special emphasis on biosensor technology.This would help in translating the latest development in CRP detection in the clinical diagnosis of inflammatory conditions at an early onset of the diseases.

Mechanisms of C-reactive protein, interleukin-6 and soluble CD40L blood concentration changes after coronary stent implantation

Background: The pathway linking inflammation and thrombosis has been extensively studied. Experimental data support that arterial thrombosis also induces a detectable inflammatory response, which in turn, activates prothrombotic pathways closing a vicious circle that interconnects inflammation and thrombosis. Aim: We designed this study to investigate the causes of inflammatory markers increase after coronary angioplasty. Methods: We analyzed the interrelationship of thrombotic and inflammatory markers and the effect of blocking thrombus formation on the inflammatory response in 50 patients undergoing high thrombotic risk coronary angioplasty. The relationship of platelet number to soluble CD40 Ligand, Interleukin-6 and C-reactive protein blood levels was studied. Half of the study population was treated with standard antithrombotic drugs and the other half with the standard therapy plus platelet GP IIb-IIIa receptor inhibitor Eptifibatide. Results: There was a clear correlation between basal platelet count and sCD40L basal levels, post-angioplasty sCD40L increase and post-angioplasty IL-6 levels and post-angioplasty IL-6 levels with post-angioplasty CRP levels. Postangioplasty CRP, IL-6 and sCD40L blood levels were influenced by GP IIb-IIIa treatment in patients with angiographic thrombus. Conclusion: Platelet aggregation induces a proinflammatory response which is blocked by a GP IIb-IIIa inhibitor agent, particularly in patients with patent angiographic thrombus.

Diagnostic and prognostic significance of the lymphocyte/C-reactive protein ratio,neutrophil/lymphocyte ratio,and D-dimer values in patients with COVID-19

In this study,our aim was to examine the diagnostic and prognostic significance of lymphocyte/C-reactiveprotein ratio(LCR),neutrophil/lymphocyte ratio(NLR)and D-dimer parameters in COVID-19 infection.The LCR,NLR,neutrophil count,mean platelet volume(MPV),C-reactive protein(CRP),and D-dimer parameters wereevaluated retrospectively.This was a retrospective cohort study with 1000 COVID-19 positive and 1000 healthycontrol groups,all over the age of 18 years.Odds ratio(OR)and 95%confidence interval(CI)values were calculatedfor each parameter found to be statistically significant in the univariate and multivariate logistic regression models.Herein,127(12.7%)of the COVID-19^(+)patients,whose data was included in this study,died.The neutrophil,MPV,CRP,D-dimer,and NLR values were higher in the COVID-19^(+)/deceased group than in the COVID-19^(+)/alive andcontrol groups(p<0.001,p<0.001,p<0.001,p<0.001,p<0.001).The lymphocyte and LCR values were lower inthe COVID-19^(+)/deceased group than in the COVID-19^(+)/alive and control groups(p<0.001,p<0.001).Variableswith statistically significance in predicting COVID-19 infection were lymphocyte,LCR,D-dimer,NLR,CRP,MPV,PLT,and neutrophil values.Statistically significant variables in predicting mortality due to COVID-19 were LCR,CRP,NLR,lymphocyte,D-dimer,neutrophil,and MPV values.A low LCR and high NLR are associated with thepresence,prognosis,and mortality due to COVID-19.LCR and NLR parameters can thus be used in clinicalmonitoring to reduce morbidity and mortality rates.

Correlation between LDL-cholesterol and C-reactive protein among an apparently healthy population in the city of Athens

Background: The atherogenic LDL is an impor-tant generative cause for the endothelial dys-function and the configuration of the athero-sclerotic lesions. CRP is a sensitive marker of inflammation on the vascular wall, but also seems to participate in the atheromatic process. The correlation between LDL and CRP could form valuable guidelines for the initiation of a treatment with statins for individuals with an increased risk of ischemic incidents. Objectives: The aim of the study was to investigate a pos-sible correlation between LDL and CRP in an important number of apparently healthy indi-viduals. Methods: The study material consisted of the test results of 260 male and 484 female adults with normal LDL levels who were clini-cally healthy. The correlation between the LDL and the CRP values of this group was investi-gated in this group and CRP was compared with the respective values of a group of 60 male and 204 female adults with elevated LDL levels. Re-sults: It was ascertained that there is not a sta-tistically important correlation between LDL and CRP values in all groups (men, women, total) of the population with normal LDL levels. Addi-tionally, the CRP mean values were not statisti-cally different between the individuals with normal and raised LDL. Conclusion: A number of causes are incriminated for the results. More studies are definitely needed for the confirma-tion of the results, particularly if the findings could lead to the formation of guidelines for the application of a treatment in people with normal LDL levels but increased CRP levels.

Efficacy of Jiangzhi Xiaoban tablet(降脂消斑片)on toll-like receptor 4/nuclear factor-kappa B/nod-like receptor protein 3 signaling pathway in mice with atherosclerosis induced by high-fat diet

OBJECTIVE:To study the effect of Jiangzhi Xiaoban tablet(降脂消斑片,JZXB)on toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/Nod-like receptor protein 3(NLRP3)signaling pathway expression in atherosclerosis(AS)mice by establishing a mouse model of AS,and to explore its mechanism of prevention and treatment of AS.METHODS:Sixty-four male C57BL/6J mice were randomly divided into two groups,12 in the normal control group and 52 in the model group(MOD).Seven weeks later,two mice in each of the above two groups were randomly sacrificed,and the whole aortic tissue of the mice was taken out for hematoxylin-eosin staining.After successful modeling,50 mice in the modeling group were randomly divided into 5 groups:MOD,atorvastatin group(ATO),low-dose group of JZXB(JZXB-L),middle-dose group of JZXB(JZXB-M),and high-dose group of JZXB(JZXB-H),10 mice in each group.The mice in each group were killed after 6 weeks of preventive administration.HE staining was used to observe the pathological changes of aorta in AS mice.The levels of serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected by automatic biochemical analyzer.The levels of inflammatory factor interleukin-1β(IL-1β)were detected by enzyme linked immunosorbent assay.The expression of TLR4,NF-κB and NLRP3 proteins in aortic tissue was detected by immunohistochemistry.RESULTS:Compared with the MOD,the levels of serum TC,TG and LDL-C in the JZXB-H and ATO were significantly decreased,while the level of HDL-C was significantly increased.The levels of serum TG,LDL-C in the JZXB-M were significantly decreased,and the level of HDL-C was significantly increased.Compared with the MOD,the levels of IL-1βwere significantly decreased,aortic lesions were significantly improved,and the expression of TLR4,NF-κB,and NLRP3 proteins in the aortic tissue was significantly decreased in the JZXB-H,JZXB-M,and ATO.CONCLUSION:JZXB has inhibitory effect on atherosclerosis in mice,and its mechanism may be through regulating the TLR4/NF-κB/NLRP3 signaling pathway and reducing the inflammatory response,so as to play a role in inhibiting atherosclerosis.

Prognostic role of C-reactive protein to albumin ratio in lung cancer:An updated systematic review and meta-analysis

Background: C-reactive protein to albumin ratio(CRP/Alb ratio,CAR)has been suggested as a potential prognostic biomarker in lung cancer.This updated systematic review and meta-analysis aimed to assess the association between CAR and lung cancer prognosis in current literature.Methods: A systematic search of databases was conducted to identify relevant studies published up to April 2023.Pooled hazard ratios(HRs)and 95%confidence intervals(CIs)were calculated to assess the association between CAR and overall survival(OS)and progression-free survival(PFS)and recurrence-free survival(RF)in lung cancer patients.Results: This meta-analysis includes 16 studies with a total of 5337 patients,indicating a significant association between higher CAR and poorer OS,PFS,and RFS in lung cancer patients,with a pooled HR of 1.78(95%CI=1.60-1.99),1.57(95%CI=1.36-1.80),and 1.97(95%CI=1.40-2.77),respectively.Conclusions: This updated meta-analysis provides evidence for the potential prognostic role of CAR in lung cancer,suggesting its utility as an effective and noninvasive biomarker for identifying high-risk patients and informing treatment decisions in a cost-effective manner.However,further large-scale studies will be necessary to establish the optimal cut-off value for CAR in lung cancer and confirm the present findings.

Systemic inflammation in colorectal cancer: Underlying factors,effects, and prognostic significance

Systemic inflammation is a marker of poor prognosis preoperatively present in around 20%-40%of colorectal cancer patients.The hallmarks of systemic inflammation include an increased production of proinflammatory cytokines and acute phase proteins that enter the circulation.While the low-level systemic inflammation is often clinically silent,its consequences are many and may ultimately lead to chronic cancer-associated wasting,cachexia.In this review,we discuss the pathogenesis of cancer-related systemic inflammation,explore the role of systemic inflammation in promoting cancer growth,escaping antitumor defense,and shifting metabolic pathways,and how these changes are related to less favorable outcome.

Fecal lactoferrin accurately reflects mucosal inflammation in inflammatory bowel disease

BACKGROUND Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin(FC)and fecal lactoferrin(FL)in monitoring inflammatory bowel diseases(IBD)-Crohn's disease(CD)and ulcerative colitis(UC).However,their correlation to endoscopic scores,disease severity and affected intestinal surface has not been extensively investigated.AIM To correlate FL,and for comparison white blood cell(WBC)and C-reactive protein(CRP),with endoscopic scores,disease extent and location in CD and UC.METHODS Retrospective analysis in 188 patients who had FL,CRP and WBC determined within 30 d of endoscopy.Disease location,disease extent(number of intestinal segments involved),disease severity(determined by endoscopic scores),timing of FL testing in relation to colonoscopy,as well as the use of effective fast acting medications(steroids and biologics)between colonoscopy and FL measurement,were recorded.RESULTS In 131 CD and 57 UC patients,both CRP and FL-but not WBC-distinguished disease severity(inactive,mild,moderate,severe).In patients receiving fastacting(steroids or biologics)treatment in between FL and colonoscopy,FL showed a higher correlation to endoscopic scores when tested before vs after the procedure(r=0.596,P<0.001,vs r=0.285,P=0.15 for the Simple Endoscopic Score for CD;and r=0.402,P=0.01 vs r=0.054 P=0.84 for Disease Activity Index).Finally,FL was significantly correlated with the diseased mucosal surface(colon-ileocolon>small bowel)and the number of inflamed colon segments.CONCLUSION FL and CRP separated disease severity categories with FL showing lower discriminating P-values.FL showed a close correlation with the involved mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before the procedure–this indicating that inflammatory activity changes associated with therapy might be rapidly reflected by FL levels.FL can accurately and timely characterize intestinal inflammation in IBD.

Effect of high dose intravenous ascorbic acid on the level of inflammation in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a major inflammatory joint disease that causes cartilage destruction, bone erosions, and joint destruction. Oxidative stress is elevated in RA patients implying reactive oxygen species (ROS) are possible mediators of tissue damage. ROS trigger a cascade of events through nuclear factors’ activation (NF-kappa B), which up-regulates gene expression of pro-inflammatory cytokines that mediate the immune responses causing inflammation. As ascorbic acid can reduce oxidative stress, decrease production of pro-inflammatory cytokines, and suppress the activation of NF-kappa B, we suggest that millimolar concentration of ascorbic acid may be useful in RA treatment. In our study we analyzed the effect of intravenous vitamin C (IVC) treatment on eleven subjects with RA. Our data suggest that IVC therapy with dosages of 7.5 g - 50 g can reduce inflammation. The level of inflammation as measured by C-reactive protein levels was decreased on average by 44%. Based on our pilot study, we hypothesize that IVC therapy can be a useful strategy in treating RA.

Residual Cardiovascular Risk—Is Inflammation the Primary Cause?

Every cardiovascular clinical trial that has examined the beneficial effects of lowering LDL cholesterol to prevent cardiovascular events has demonstrated residual cardiovascular risk in the interventional treatment group. Residual risk is the term applied to the cardiovascular events (e.g., myocardial infarction, stroke, and cardiovascular death) that occur in spite of being on “optimal” medical therapy. This term is usually applied to secondary intervention studies,?i.e., lipid lowering treatments in subjects who have already had at least one cardiovascular event. Studies that described residual risk have attributed it, at least in part, to the fact that the LDLc has not been lowered sufficiently to stop atherosclerotic plaque formation and rupture into the arterial lumen. However, a recent cardiovascular intervention clinical trial which achieved a very low group median LDLc of 30 mg/dl still demonstrated significant residual risk. Of more importance to reducing residual risk may be addressing the ongoing inflammation in the coronary arteries that results in cellular liberation of cytokines and proteases that attack the atherosclerotic plaque’s fibrous cap. Recent studies have shown that inflammation may act independently of LDL to cause cardiovascular events. This article provides evidence that inflammation is the primary cause of residual risk and will need to be treated as aggressively as LDL lowering if CVD events in the post treatment period are to be significantly reduced. Addressing major risk factors including obesity, diabetes, smoking, hypertension and hyperlipidemia are critical to reducing inflammation. Statins and aspirin are the mainstay medications to reduce ongoing inflammation. However, newer pharmaceuticals may also be required to reduce inflammation to undetectable levels. Targeting inflammation to eradicate residual cardiovascular risk will be the next therapeutic challenge facing primary care physicians.