Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI<2.3×10^(3)/L(4 vs 18 mo;P<0.000).Among 21 patients with>5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not lose>5%of their weight had an OS of 20 mo,compared to 11 mo for those who did(P<0.001).No association was found between carbohydrate antigen 19-9 levels≥1000 U/mL and weight loss.CONCLUSION A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss.An elevated SIRI is suggested as a predictor of survival,emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.

Assessment of systemic immune-inflammatory index and other inflammatory parameters in predicting mortality in patients with acute cholecystitis:A retrospective observational study

Objective:To investigate the effectiveness of the systemic immune-inflammatory(SII)index and other inflammatory parameters in predicting mortality among patients with acute cholecystitis(AC).Methods:279 Patients presented to the emergency department with abdominal pain and diagnosis of AC between September 2021 and September 2023 were included in the study.Demographic data,laboratory parameters,clinical follow-ups,and outcomes of the patients were recorded.Results:The mean age of the patients was(55.0±16.3)years and 36.6%were male.63.8%Had gallbladder/choledochal stones and 49.5%underwent surgery.The mortality rate was 6.1%.Advanced age(P=0.170)and prolonged hospitalization(P=0.011)were statistically significant risk factors for mortality.Decreased lymphocyte count(P=0.020)and increased C-reactive protein(CRP)levels(P=0.033)were found to be risk factors for mortality.According to the mortality predictor ROC analysis results,the cut-off for SII index was 3138(AUC=0.817,sensitivity=70.5%,specificity=84.7%),the cut-off for neutrophil count was 15.28×10^(3)/mm^(3)(AUC=0.761,sensitivity=52.9%,specificity=95.0%),the cut-off for leukocyte count was 19.0×10^(3)/mm^(3)(AUC=0.714,sensitivity=52.9%,specificity=98.0%),cut-off for CRP was 74.55(AUC=0.758,sensitivity=70.5%,specificity=79.0%),cut-off for aspartate transaminase(AST)was 33.0 IU/L(AUC=0.658,sensitivity=82.3%,specificity=50.3%).Conclusions:The SII index may be a good predictor of mortality with high sensitivity and specificity.Elevated levels of neutrophils,leukocytes,CRP,and AST are other inflammatory parameters that can be used to predict mortality associated with AC.

Correlation between preoperative systemic immune inflammation index, nutritional risk index, and prognosis of radical resection of liver cancer

BACKGROUND Radical surgery is the most commonly used treatment for hepatocellular carcinoma(HCC).However,the surgical effect remains not ideal,and prognostic evaluation is insufficient.Furthermore,clinical intervention is rife with uncertainty and not conducive to prolonging patient survival.AIM To explore correlations between the systemic immune inflammatory index(SII)and geriatric nutritional risk index(GNRI)and HCC operation prognosis.METHODS This retrospective study included and collected follow up data from 100 HCC.Kaplan–Meier survival curves were used to analyze the correlation between SII and GNRI scores and survival.SII and GNRI were calculated as follows:SII=neutrophil count×platelet count/lymphocyte count;GNRI=[1.489×albumin(g/L)+41.7×actual weight/ideal weight].We analyzed the predictive efficacy of the SII and GNRI in HCC patients using receiver operating characteristic(ROC)curves,and the relationships between the SII,GNRI,and survival rate using Kaplan–Meier survival curves.Cox regression analysis was utilized to analyze independent risk factors influencing prognosis.RESULTS After 1 year of follow-up,24 patients died and 76 survived.The area under the curve(AUC),sensitivity,specificity,and the optimal cutoff value of SII were 0.728(95%confidence interval:0.600-0.856),79.2%,63.2%,and 309.14,respectively.According to ROC curve analysis results for predicting postoperative death in HCC patients,the AUC of SII and GNRI combination was higher than that of SII or GNRI alone,and SII was higher than that of GNRI(P<0.05).The proportion of advanced differentiated tumors,tumor maximum diameter(5–10 cm,>10 cm),lymph node metastasis,and TNM stage III-IV in patients with SII>309.14 was higher than that in patients with SII≤309.14(P<0.05).The proportion of patients aged>70 years was higher in patients with GNRI≤98 than that in patients with GNRI>98(P<0.05).The 1-year survival rate of the SII>309.14 group(compared with the SII≤309.14 group)and GNRI≤98 group(compared with the GNRI>98 group)was lower(P<0.05).CONCLUSION The prognosis after radical resection of HCC is related to the SII and GNRI and poor in high SII or low GNRI patients.

The modified systemic inflammation score is a predictor of ICU admission of COVID-19 patients

Objective:To evaluate the effect of the modified systemic inflammation score(mSIS)on prognosis in patients diagnosed with COVID-19.Methods:In this retrospective cross-sectional study,181 patients were selected and divided into two groups:patients with and without admission to the intensive care unit(ICU).An albumin level of≥4.0 g/dL and lymphocyte-to-monocyte ratio(LMR)of≥3.4 was scored 0,an albumin level of<4.0 g/dL or LMR of<3.4 was scored 1,and an albumin level of<4.0 g/dL and LMR of<3.4 was scored 2.Results:A total of 242 COVID-19 positive patients were initially included in this study.Of these patients,61 were excluded and 181 patients remained.Among the 181 participants,94(51.9%)were female,and the median age was 61(51,75)years.The mSIS scale ranged from 0 to 2.After analysis,the median score was 0(0,0)in the non-ICU group and 2(0,2)in the ICU group(P<0.001).The median white blood cell,lymphocyte counts,and albumin levels were lower in the ICU group(P<0.001,P<0.001,and P<0.001,respectively).In logistic regression analysis lymphocytopenia(OR=5.158,95%CI=1.249-21.304,P=0.023),hypoalbuminemia(OR=49.921,95%CI=1.843-1352.114,P=0.020),AST elevation(OR=3.939,95%CI=1.017-15.261,P=0.047),and mSIS=2(OR=5.853,95%CI=1.338-25.604,P=0.019)were identified as independent predictors of ICU admission.Conclusion:The mSIS can be used as an independent parameter for establishing the intensive care needs of patients with COVID-19.

Effects of altering the ratio of C16:0 and cis-9 C18:1 in rumen bypass fat on growth performance, lipid metabolism, intestinal barrier, cecal microbiota, and inflammation in fattening bulls

Background C16:0 and cis-9 C18:1 may have different effects on animal growth and health due to unique metabolism in vivo.This study was investigated to explore the different effects of altering the ratio of C16:0 and cis-9 C18:1 in fat supplements on growth performance,lipid metabolism,intestinal barrier,cecal microbiota,and inflammation in fattening bulls.Thirty finishing Angus bulls(626±69 kg,21±0.5 months)were divided into 3 treatments according to the randomized block design:(1)control diet without additional fat(CON),(2)CON+2.5%palmitic acid calcium salt(PA,90%C16:0),and(3)CON+2.5%mixed fatty acid calcium salt(MA,60%C16:0+30%cis-9 C18:1).The experiment lasted for 104 d,after which all the bulls were slaughtered and sampled for analysis.Results MA tended to reduce 0–52 d dry matter intake compared to PA(DMI,P=0.052).Compared with CON and MA,PA significantly increased 0–52 d average daily gain(ADG,P=0.027).PA tended to improve the 0–52 d feed conversion rate compared with CON(FCR,P=0.088).Both PA and MA had no significant effect on 52–104 days of DMI,ADG and FCR(P>0.05).PA tended to improve plasma triglycerides compared with MA(P=0.077),significantly increased plasma cholesterol(P=0.002)and tended to improve subcutaneous adipose weight(P=0.066)when compared with CON and MA.Both PA and MA increased visceral adipose weight compared with CON(P=0.021).Only PA increased the colonization of Rikenellaceae,Ruminococcus and Proteobacteria in the cecum,and MA increased Akkermansia abundance(P<0.05).Compared with CON,both PA and MA down-regulated the m RNA expression of Claudin-1 in the jejunum(P<0.001),increased plasma diamine oxidase(DAO,P<0.001)and lipopolysaccharide(LPS,P=0.045).Compared with CON and MA,PA down-regulated the ZO-1 in the jejunum(P<0.001)and increased plasma LPS-binding protein(LBP,P<0.001).Compared with CON,only PA down-regulated the Occludin in the jejunum(P=0.013).Compared with CON,PA and MA significantly up-regulated the expression of TLR-4 and NF-κB in the visceral adipose(P<0.001)and increased plasma IL-6(P<0.001).Compared with CON,only PA up-regulated the TNF-αin the visceral adipose(P=0.01).Compared with CON and MA,PA up-regulated IL-6 in the visceral adipose(P<0.001),increased plasma TNF-α(P<0.001),and reduced the Ig G content in plasma(P=0.035).Compared with CON,PA and MA increased C16:0 in subcutaneous fat and longissimus dorsi muscle(P<0.05),while more C16:0 was also deposited by extension and desaturation into C18:0 and cis-9 C18:1.However,neither PA nor MA affected the content of cis-9 C18:1 in longissimus dorsi muscle compared with CON(P>0.05).Conclusions MA containing 30%cis-9 C18:1 reduced the risk of high C16:0 dietary fat induced subcutaneous fat obesity,adipose tissue and systemic low-grade inflammation by accelerating fatty acid oxidative utilization,improving colonization of Akkermansia,reducing intestinal barrier damage,and down-regulating NF-κB activation.

Systemic inflammation and immune response after laparotomy vs laparoscopy in patients with acute cholecystitis, complicated by peritonitis

AIM: To evaluate acute cholecystitis, complicated by peritonitis, acute phase response and immunological status in patients treated by laparoscopic or open approach. METHODS: From January 2002 to May 2012, we conducted a prospective randomized study on 45 consecutive patients (27 women, 18 men; mean age 58 years). These subjects were taken from a total of 681 patients who were hospitalised presenting similar preoperative findings: acute upper abdominal pain with tenderness, involuntary guarding under the right hypochondrium and/or in the flank; fever higher than 38 ℃, leukocytosis greater than 10 × 10 9 /L or both, and ultrasonographic evidence of calculous cholecystitis possibly complicated by peritonitis. These patients had undergone cholecystectomy for acute calculous cholecystitis,complicated by bile peritonitis. Randomly, 23 patients were assigned to laparoscopic cholecystectomy (LC), and 22 patients to open cholecystectomy (OC). Blood samples were collected from all patients before operation and at days 1, 3 and 6 after surgery. Serum bacteraemia, endotoxaemia, white blood cells (WBCs), WBC subpopulations, human leukocyte antigen-DR (HLA-DR), neutrophil elastase, interleukin-1 (IL-1) and IL-6, and C-reactive protein (CRP) were measured at 0, 30, 60, 90, 120 and 180 min, at 4, 6, 12, 24 h, and then daily (8 A.M.) until post-operative day 6.RESULTS: The two groups were comparable in the severity of peritoneal contamination as indicated by the viable bacterial count (open group = 90% of positive cultures vs laparoscopic group = 87%) and endotoxin level (open group = 33.21 ± 6.32 pg/mL vs laparoscopic group = 35.02 ± 7.23 pg/mL). Four subjects in the OC group (18.1%) and 1 subject (4.3%) in the LC group (P < 0.05) developed intra-abdominal abscess. Severe leukocytosis (range 15.8-19.6/mL) was observed only after OC but not after LC, mostly due to an increase in neutrophils (days 1 and 3, P < 0.05). This value returned to the normal range within 3-4 d after LC and 5-7 d after OC. Other WBC types and lymphocyte subpopulations showed no significant variation. On the first day after surgery, a statistically significant difference was observed in HLA-DR expression between LC (13.0 ± 5.2) and OC (6.0 ± 4.2) (P < 0.05). A statistically significant change in plasma elastase concentration was recorded post-operatively at days 1, 3, and 6 in patients from the OC group when compared to the LC group (P < 0.05). In the OC group, the serum levels of IL-1 and IL-6 began to increase considerably from the first to the sixth hour after surgery. In the LC group, the increase of serum IL-1 and IL-6 levels was delayed and the peak values were notably lower than those in the OC group. Significant differences between the groups, for these two cytokines, were observed from the second to the twenty-fourth hour (P < 0.05) after surgery. The mean values of serum CRP in the LC group on post-operative days (1 and 3) were also lower than those in the OC group (P < 0.05). Systemic concentration of endotoxin was higher in the OC group at all intra-operative sampling times, but reached significance only when the gallbladder was removed (OC group = 36.81 ± 6.4 ρg/mLvs LC group = 16.74 ± 4.1 ρg/mL, P < 0.05). One hour after surgery, microbiological analysis of blood cultures detected 7 different bacterial species after laparotomy, and 4 species after laparoscopy (P < 0.05). CONCLUSION: OC increased the incidence of bacteraemia, endotoxaemia and systemic inflammation compared with LC and caused lower transient immunological defense, leading to enhanced sepsis in the patients examined.

Hepatic steatosis,low-grade chronic inflammation and hormone/growth factor/adipokine imbalance

Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.

Even low-grade inflammation impacts on small intestinal function

Independent of the cause and location,inflammation-even when minimal-has clear effects on gastrointestinal morphology and function.These result in altered digestion,absorption and barrier function.There is evidence of reduced villus height and crypt depth,increased permeability,as well as altered sugar and peptide absorption in the small intestine after induction of inflammation in experimental models,which is supported by some clinical data.Identification of inflammatory factors which may promote the process of gastrointestinal dysfunction as well as clinical research to verify experimental observations of inflammatory modulation of gastrointestinal function are required.Moreover,nutritional strategies to support functional restitution are needed.

Role of systemic inflammation in cirrhosis:From pathogenesis to prognosis

The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver failure(ACLF). The latter syndrome has been recently described as an acute deterioration of liver function in patients with cirrhosis, which is usually triggered by a precipitating event and results in the failure of one or more organs and high short-term mortality rates. Each stage is characterized by distinctive clinical manifestations and prognoses. One of the key elements involved in cirrhosis physiopathology is systemic inflammation, recently described as one of the components in the cirrhosis-associated immune dysfunction syndrome. This syndrome refers to the combination of immune deficiency and exacerbated inflammation that coexist during the course of cirrhosis and relates to the appearance of clinical complications. Since systemic inflammation is often difficult to assess in cirrhosis patients, new objective, reproducible and readily-available markers are needed in order to optimize prognosis and lengthen survival. Thus, surrogate serum markers and clinical parameters of systemic inflammation have been sought to improve disease follow-up and management, especially in decompensated cirrhosis and ACLF. Leukocyte counts(evaluated as total leukocytes, total eosinophils or neutrophil:lymphocyte ratio) and plasma levels of procalcitonin or C-reactive protein have been proposed as prognostic markers, each with advantages and shortcomings. Research and prospective randomized studies that validate these and other markers are clearly warranted.

Association of systemic inflammation and body mass index with survival in patients with resectable gastric or gastroesophageal junction adenocarcinomas

Objective:The systemic inflammation index and body mass index(BMI)are easily accessible markers that can predict mortality.However,the prognostic value of the combined use of these two markers remains unclear.The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer.Methods:A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included.Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio(NLR).High systemic inflammation was defined as NLR≥3,and underweight was defined as BMI<18.5 kg/m2.Results:Among 2,542 patients,NLR≥3 and underweight were common[627(25%)and 349(14%),respectively].In the entire cohort,NLR≥3 or underweight independently predicted overall survival(OS)[hazard ratio(HR):1.236,95%confidence interval(95%CI):1.069–1.430;and HR:1.600,95%CI:1.350–1.897,respectively]and recurrence-free survival(RFS)(HR:1.230,95%CI:1.054–1.434;and HR:1.658,95%CI:1.389–1.979,respectively).Patients with both NLR≥3 and underweight(vs.neither)had much worse OS(HR:2.445,95%CI:1.853–3.225)and RFS(HR:2.405,95%CI:1.802–3.209).Furthermore,we observed similar results in subgroup analyses according to pathological stage,age,and postoperative chemotherapy.Conclusions:Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival.Underweight combined with severe inflammation could enhance prognostication.Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.

Systemic immune inflammation index, ratio of lymphocytes to monocytes, lactate dehydrogenase and prognosis of diffuse large Bcell lymphoma patients

BACKGROUND In malignant tumors,inflammation plays a vital role in the development,invasion,and metastasis of cancer cells.Diffuse large B-cell lymphoma(DLBCL),the most common malignant proliferative disease of the lymphatic system,is commonly associated with inflammation.The international prognostic index(IPI),which includes age,lactate dehydrogenase(LDH),number of extranodal lesions,Ann Arbor score,and Eastern Cooperative Oncology Group(ECOG)score,can evaluate the prognosis of DLBCL.However,its use in accurately identifying highrisk patients and guiding treatment is poor.Therefore,it is important to find novel immune markers in predicting the prognosis of DLBCL patients.AIM To determine the association between the systemic immune inflammation index(SII),ratio of lymphocytes to monocytes(LMR),ratio of LMR to LDH(LMR/LDH),and prognosis of patients with DLBCL.METHODS A total of 68 patients diagnosed with DLBCL,treated in our hospital between January 2016 and January 2020,were included.χ2 test,Pearson’s R correlation,Kaplan Meier curves,and Cox proportional risk regression analysis were used.The differences in the SII,LMR,and LMR/LDH among patients with different clinicopathological features were analyzed.The differences in progression-free survival time among patients with different SII,LMR,and LMR/LDH expressions and influencing factors affecting the prognosis of DLBCL patients,were also analyzed.RESULTS The LMR and LMR/LDH in patients with Ann Arbor stage III–IV,ECOG score≥2,and SII,IPI score 2–5 were significantly higher than those of patients with Ann Arbor stage I-II and ECOG score<2(P<0.05).Patients with high SII,LMR,and LMR/LDH had progression-free survival times of 34 mo(95%CI:32.52–38.50),35 mo(95%CI:33.42–36.58)and 35 mo(95%CI:33.49–36.51),respectively,which were significantly lower than those with low SII,LMR,and LMR/LDH(P<0.05);the SII,LMR,and LMR/LDH were positively correlated(P<0.05).Cox proportional risk regression analysis showed that the SII,LMR,and LMR/LDH were influencing factors for the prognosis of DLBCL patients(hazard ratio=1.143,1.665,and 1.704,respectively;P<0.05).CONCLUSION The SII,LMR,and LMR/LDH are related to the clinicopathological features of DLCBL,and they also influence the prognosis of patients with the disease.

Prognostic value of systemic immune.inflammation index in patients with gastric cancer

Background:Inflammation-based indexes have been used to predict survival and recurrence in cancer patients.Systemic immune-inflammation index(Sll) was reported to be associated with prognosis in some malignant tumors.In the present study,we aimed to explore the association between Sll and the prognosis of patients with gastric cancer.Methods:We retrospectively analyzed data from 444 gastric cancer patients who underwent gastrectomy at the First Affiliated Hospital of Sun Yat-sen University between January 1994 and December 2005.Preoperative Sll was calculated.The Chi square test or Fisher's exact test was used to determine the relationship between preoperative Sll and clinicopathologic characteristics.Overall survival(OS) rates were estimated using the Kaplan-Meier method,and the effect of Sll on OS was analyzed using the Cox proportional hazards model.Receiver operating characteristic(ROC)curves were used to compare the predictive ability of Sll,NLR,and PLR.Results:Sll equal to or higher than 660 was significantly associated with old age,large tumor size,unfavorable Borrmann classification,advanced tumor invasion,lymph node metastasis,distant metastasis,advanced TNM stage,and high carcino-embryonic antigen level,high neutrophil-lymphocyte ratio,and high platelet-lymphocyte ratio(all P<0.05).High Sll was significantly associated with unfavorable prognosis(P<0.001) and Sll was an independent predictor for OS(P=0.015).Subgroups analysis further showed significant associations between high Sll and short OS in stage Ⅰ,Ⅱ,Ⅲ subgroups(all P<0.05).Sll was superior to NLR and PLR for predicting OS in patients with gastric cancer.Conclusion:Preoperative Sll level is an independent prognostic factor for OS in patients with gastric cancer.

Efficacy of Ulinastatin Combined with Continuous Renal Replacement Therapy in the Treatment of Sepsis Acute Kidney Injury and Its Effects on Systemic Inflammation, Immune Function and miRAN Expression

Objective: To research the effectiveness of ulinastatin in combination with continuous renal replacement therapy in treating sepsis acute kidney injury and its effect on systemic inflammation, immune function and miRAN expression. Methods: The 84 patients who were diagnosed with sepsis complicated by acute kidney injury in our hospital between May 2020 and June 2022 were chosen and randomly assigned to the study group (n = 42) and the control group (n = 42). Ulinastatin in combination with continuous renal replacement therapy was administered to the study group, whereas the control group was administered with continuous renal replacement therapy alone. Both groups’ clinical effects were observed. The levels of blood urea nitrogen (BUN), serum creatinine (SCr), tumor necrosis factor-α (TNF-α), high sensitivity Creactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1), IgG, IgA, IgM, expression levels of miR-233 and miR-10a were compared among both the groups, pre-, and post-treatment. Results: The study group’s overall effectiveness rate was higher that is 95.24%, in comparison to the control group’s 78.57%, and this difference was statistically significant (P α, hs-CRP, VCAM-1, and miR-233 and miR-10a expression levels in both the study and control groups were decreased, however, the study group had reduced levels in comparison to the control group, with statistically significant differences (P P Conclusion: Ulinastatin in combination with continuous renal replacement therapy for treating sepsis acute kidney injury exhibits a positive effect and can significantly improve the systemic inflammation and immune function in patients.

Serum Markers of Systemic Inflammation in Patients with Pulmonary Tuberculosis

Serum markers of systemic inflammation （SAA （serum amyloid protein A）, CRP （C-reactive protein）, cq-AT （ct l-antitripsin）, Hp （haptoglobin） and F （fibrinogen）） have been studied in 317 patients with pulmonary tuberculosis. It was established that sensitivity of SAA as an activity marker was higher than of other acute phase reactants, because its levels were increased in 98.8% patients, whereas the level of CRP exceeded the norm in 80.8%, α1-AT--in 59.3%, Hp----in 43.5% and F--in 63.1% cases. The degree of increase of acute phase reactants directly related to the expressiveness of tuberculosis intoxication, the extent of the process in the lung and the quantity of MTB （M. tuberculosis） in sputum. We concluded that SAA was a useful marker of the process activity in patients with pulmonary tuberculosis and its sensitivity was higher than that of other acute phase reactants.

Effects of Meglumine Cyclic Adenylate Pretreatment on Systemic inflammatory Response Syndrome Induced by Lipopolysaccharide in Rats

Studies showed that the use of cyclic adenosine monophosphate(cAMP) substitutes or intracellular c AMP activators increased intracellular cAMP level, causing anti-inflammatory effects. This study was to investigate the effects of pretreatment with meglumine cyclic adenylate(MCA), a compound of meglumine and cAMP, on systemic inflammation induced by lipopolysaccharide(LPS) in rats. Eighteen adult male Sprague-Dawley rats were randomly divided into 3 groups(n=6 each): control group(NS group), LPS group(LPS group) and LPS with MCA pretreatment group(MCA group). Systemic inflammation was induced with LPS 10 mg/kg injected via the femoral vein in LPS and MCA groups. In MCA group, MCA 2 mg/kg was injected via the femoral vein 20 min before LPS injection, and the equal volume of normal saline was given in NS and LPS groups at the same time. Three hours after LPS injection, the blood samples were taken from the abdominal aorta for determination of plasma concentrations of TNF-α, IL-1, IL-6, IL-10, cAMP by ELISA and NF-κBp65 expression by Western blotting. The experimental results showed that inflammatory and antiinflammatory indices were increased in LPS group compared to NS group; inflammatory indices were declined and anti-inflammatory indices were increased in MCA group relative to LPS group. Our study suggested that MCA pretreatment may attenuate LPS-induced systemic inflammation.

Systemic Inflammatory Markers and Disease Severity in Chronic Obstructive Pulmonary Disease—The Effect of Acute Exercise and Pulmonary Rehabilitation

Background: Decreased physical capacity and increased systemic inflammatory response are frequently observed in patients with chronic obstructive pulmonary disease (COPD). The relationship between the inflammatory response and disease severity and the immunological response to exercise were addressed in COPD. Objective: The first objective was to identify systemic biomarkers and their relationship with COPD severity. The second objective was to examine the effect of both acute exercise and pulmonary rehabilitation on these biomarkers. Methods: Forty subjects participated in the study. Thirty-two patients with moderate or severe COPD and 8 healthy non-smokers completed the study. Spirometry was preformed. Physical capacity was determined by a progressive symptom-limited cycle ergo meter (incremental) test. Blood samples were analyzed for C-reactive protein (CRP), pro-inflammatory cytokines (IL-6, TNF-α), pro-fibrotic cytokines (TGF-β) and oxidative burst in circulating leukocytes before and after exercise, and before and after pulmonary rehabilitation. Results: IL-6, CRP, WCC and TGF-β were higher in COPD (p α, CRP and TGF-β were negatively related to forced expiratory volume in 1 s (FEV1) (r = 0.4054, 0.3221, 0.1528, 0.1846 and 0.1187, respectively). Acute exercise increased circulating leucocytes and oxidative stress in both groups (p = 0.000, 0.0049 respectively), while IL-6 was increased in COPD group ((p = 0.0115) and circulating TNF-α in healthy control (p = 0.0369). Pulmonary rehabilitation didn’t modify the levels of inflammatory mediators. Conclusions: Reduced lung function is associated with increased levels of systemic inflammatory markers and acute exercise can further increase this inflammatory response. However pulmonary rehabilitation is unlikely to exacerbate systemic inflammation in COPD.

Inflammation, oxidative stress and renin angiotensin system in atherosclerosis

Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.

Relationships between blood chromium exposure and liver injury:Exploring the mediating role of systemic inflammation in a chromate-exposed population

Hexavalent chromium and its compounds are prevalent pollutants,especially in the work environment,pose a significant risk for multisystem toxicity and cancers.While it is known that chromium accumulation in the liver can cause damage,the dose-response relationship between blood chromium(Cr)and liver injury,as well as the possible potential toxic mechanisms involved,remains poorly understood.To address this,we conducted a follow-up study of 590 visits from 305 participants to investigate the associations of blood Cr with biomarkers for liver injury,including serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),and direct bilirubin(DBIL),and to evaluate the mediating effects of systemic inflammation.Platelet(PLT)and the platelet-to-lymphocyte ratio(PLR)were utilized as biomarkers of systemic inflammation.In the linear mixed-effects analyses,each 1-unit increase in blood Cr level was associated with estimated effect percentage increases of 0.82%(0.11%,1.53%)in TBIL,1.67%(0.06%,3.28%)in DBIL,0.73%(0.04%,1.43%)in ALT and 2.08%(0.29%,3.87%)in AST,respectively.Furthermore,PLT mediated 10.04%,11.35%,and 10.77%increases in TBIL,DBIL,and ALT levels induced by chromate,respectively.In addition,PLR mediated 8.26%and 15.58%of the association between blood Cr and TBIL or ALT.These findings shed light on the mechanisms underlying blood Cr-induced liver injury,which is partly due to worsening systemic inflammation.

Link between periodontitis and diabetic retinopathy:Inflammatory pathways and clinical implications

The bidirectional relationship between periodontitis and type 2 diabetes mellitus has been well-established.However,the underlying molecular mechanisms remain unclear.Diabetic retinopathy(DR)is an important complication of diabetes,but there are few studies on the relationship between DR and periodontitis,especially on the intrinsic inflammatory pathway mechanism.This article reviews the latest clinical data on how diabetes promotes susceptibility to periodontitis from the epidemiological and molecular perspectives,with a special focus on the key roles of systemic inflammation and endothelial dysfunction in the interplay between DR and periodontitis.Comprehension of the intertwined pathogenesis of DR and periodontitis can better guide the development of comprehensive management strategies for glycemic control and periodontal health,with the aim of mitigating the progression of DR and enhancing overall well-being.

Prognostic impact of preoperative nutritional and immune inflammatory parameters on liver cancer

The immune response to tissue damage or infection involves inflammation,a multifaceted biological process distinguished by immune cell activation,mediator secretion,and immune cell recruitment to the site of injury.Several blood-based immune-inflammatory biomarkers with prognostic significance in malignancies have been identified.In this issue of the World Journal of Gastrointestinal Surgery,they examined the prognosis of liver cancer radical resection in relation to pre-operative systemic immune-inflammation and nutritional risk indices.Comparing older and younger individuals often reveals compromised nutritional and immu-nological statuses in the former.Therefore,performing preoperative evaluations of the nutritional status and immunity in geriatric patients is critical.In addition to being a primary treatment modality,radical resection is associated with a sig-nificant mortality rate following surgery.Insufficient dietary consump-tion and an elevated metabolic rate within tumor cells contribute to the increased proba-bility of malnutrition associated with the ailment,consequently leading to a sub-stantial deterioration in prognosis.Recent studies,reinforce the importance of nu-tritional and immune-inflammatory biomarkers.Prior to surgical intervention,geriatric nutritional risk and systemic immune-inflammatory indices should be prioritized,particularly in older patients with malignant diseases.