Amalgamation of systemic inflammatory response syndrome score with C-reactive protein level in evaluating acute pancreatitis severity in children

Background and aim: Systemic inflammatory response syndrome (SIRS) has to do with how the body reacts to injury. Herein, we analyzed the clinical features of acute pancreatitis (AP) in children with SIRS complication and investigated the role of SIRS score combined with C-reactive protein (CRP) level in assessing AP severity in children.

Methods: This retrospective cohort study involved 111 children hospitalized with AP at the Children's Hospital of Zhejiang University School of Medicine between January 2012 and August 2017. Presence of SIRS, demographic data, clinical information and laboratory test results on admission were statistically examined.

Results: Out of the 111 AP cases, 45 were diagnosed with SIRS. Differences in CRP, interleukin-6 (IL-6), age, temperature, heart rate (HR), white blood cell (WBC), neutrophil count (NC), body mass index (BMI), duration of onset of disease symptoms as well as cases requiring intensive care unit (ICU) treatment were significantly higher in patients with SIRS than those without SIRS (p?p?p?=?.02) and fever (OR?=?3.56, p?=?.007). SIRS was an independent predictor for AP severity (OR?=?10.820, p?=?.005). The optimal cut-off value of CRP was 27.5?mg/L for severe AP classification according to receiver operating characteristic (ROC) (area under curve was 0.733).

Conclusion: Amalgamation of SIRS criterion with CRP level potentially plays an important role in assessing AP severity in children.     

Predictors of new-onset diabetic ketoacidosis in patients with moderate to severe COVID-19 receiving parenteral glucocorticoids: A prospective single-centre study among Indian type 2 diabetes patients

Background and aimCOVID-19 infection predisposes to diabetic ketoacidosis(DKA); whether glucocorticoids enhances this risk is unknown.We aimed to study the occurrence of DKA after initiating glucocorticoids in patients with type 2 diabetes mellitus(T2DM) and moderate-to-severe COVID-19, and identify predictors for it.MethodsPatients with T2DM and moderate or severe COVID-19 infection were prospectively observed for development of new-onset DKA for one week following initiation of parenteral dexamethasone. Clinical and biochemical parameters were compared between those who developed DKA (Group A) and those who didnot (Group B). Logistic regression was done to identify independent risk-factors predicting DKA; ROC-curve analysis to determine cut-offs for the parameters in predicting DKA.ResultsAmongst 302 patients screened, n = 196 were finally included, of whom 13.2% (n = 26,Group A) developed DKA. Patients in Group A were younger, had lower BMI, increased severity of COVID-19 infection, higher HbA1c%, CRP, IL-6, D-dimer and procalcitonin at admission (p_all < 0.02). Further, admission BMI (OR: 0.43, CI: 0.27–0.69), HbA1c % (OR: 1.68, CI: 1.16–2.43) and serum IL-6 (OR: 1.02, CI: 1.01–1.03) emerged as independent predictors for DKA. Out of these, IL-6 levels had the highest AUROC (0.93, CI: 0.89–0.98) with a cut-off of 50.95 pg/ml yielding a sensitivity of 88% and specificity of 85.2% in predicting DKA.ConclusionThere is significant incidence of new-onset DKA following parenteral glucocorticoids in T2DM patients with COVID-19, especially in those with BMI <25.56 kg/m², HbA1c% >8.35% and IL-6 levels >50.95 pg/ml at admission.     

The correlations between C-reactive protein and MRI-detected inflammation in patients with axial spondyloarthritis: a systematic review and meta-analysis

Background

C-reactive protein (CRP) and magnetic resonance imaging (MRI) are widely used to monitor inflammation in patients with axial spondyloarthritis (axSpA), but the relationship between CRP and MRI-detected inflammation is incompletely understood. The present study was undertaken to assess correlations between CRP and MRI-detected inflammation in axSpA.

Materials and methods

A systematic literature search was performed (Medline, Embase, and Cochrane Library) to identify relevant studies concerning CRP and MRI-detected inflammation in axSpA patients. The MRI-detected inflammation was evaluated by MRI-based disease activity score (DAS). The correlation between CRP and MRI-based DAS was integrated by random-effect models.

Results

Eighteen studies reported a total of 1392 axSpA patients which were included in this meta-analysis. CRP was significantly associated with spinal MR DAS (r=0.226, 95%CI [0.149, 0.291], p<0.001, I²=23%). We also found a moderate correlation between CRP change and spinal MR DAS change (r[ASspiMRI-a]=0.354, 95%CI [0.282, 0.422], p<0.001, I²=48%; r[SPARCC]=0.544, 95%CI [0.345, 0.701], p<0.001, I²=19%). CRP at baseline was negatively associated with improvement in spinal MR DAS (r= − 0.327, 95%CI [−0.397, −0.264], p<0.001, I²=0%). However, no significant association was found between CRP and sacroiliac joint (SIJ) MR DAS.

Conclusions

In axSpA patients, CRP is associated with MRI-detected inflammation in the spine but not in SIJ. We speculate that CRP could be a reasonable index to reflect spinal inflammation. Therefore, we suggest it is not essential to repeat spinal MRI in a short term, while SIJ MRI may be necessary to provide additional information on inflammation.

Mononuclear histocompatibility leukocyte antigen-DR expression in the early phase of acute pancreatitis.

BACKGROUND: In acute pancreatitis (AP), several studies indicated that the balance between pro- and anti-inflammatory mediators is more important than the levels of proinflammatory response alone. This balance may be reflected by the expression of monocyte histocompatibility leukocyte antigen (HLA)-DR, with a low concentration indicating an excess of anti-inflammatory stimuli and relative immunodeficiency. We investigated the time course of HLA-DR expression in the early phase of AP and the relationship to markers of inflammation, severity of the disease, organ function, septic complications and outcome during AP. METHODS: The expression of HLA-DR on peripheral monocytes was measured in 74 patients by flow cytometry and serum IL-6 was determined by using an immunochemiluminescence assay obtained 24 h, 48 h, 72 h, 7 days, 10 days and 14 days after admission in parallel with clinical data collection. 25 patients had mild disease (grade 1), 31 had severe disease but recovered without organ failure (grade 2) and 18 had severe disease and developed organ failure (grade 3). RESULTS: In 49 patients with severe disease, 11 patients suffered from sepsis, and 3 of them died during the hospital stay. During the first 14 days of AP, the percentage of HLA-DR in AP was significantly below the normal range of healthy subjects, it dropped to the lowest level on day 3, but then gradually recovered from the prophase depression. The HLA-DR expression decreased in the order grade 3 < grade 2 < grade 1 (p < 0.001). We also observed a significant inverse correlation between the percentage of HLA-DR+ and AP severity as assessed by APACHE-II scores (r = 0.754, p < 0.001) and MODS score (r = 0.675, p < 0.001). The peak of systemic inflammatory reaction, documented by maximum serum concentration of CRP, coincided with the nadir of HLA-DR suppression. Moreover, IL-6 and CRP serum concentrations were inversely correlated with HLA-DR expression over the entire observation period. Persistent HLA-DR suppression and a second decrease in HLA-DR expression are associated with septic complications and poor outcome. CONCLUSION: Immune suppression develops early and rapidly in patients with AP, and the degree is parallel with the severity of the disease. Decreases in HLA-DR expression occurred simultaneously with signs of hyperinflammation in the early phase of AP, and persistent HLA-DR suppression and a second decrease in HLA-DR expression are associated with septic complications and poor outcome.     

Hypoxemia and obesity modulate plasma C-reactive protein and interleukin-6 levels in sleep-disordered breathing

C-reactive protein (CRP) and interleukin-6 (IL-6) are pro-inflammatory proteins and important risk factors for atherosclerosis. Plasma CRP levels in snoring children may or may not be elevated. Since obesity is prevalent among snoring children and is associated with elevated CRP levels, we aimed to investigate the relative contributions of sleep-disordered breathing (SDB) and obesity to the inflammatory processes in snoring children in this prospective study. Two hundred forty-four children (mean age 8.9 ± 3.4 years) underwent polysomnographic evaluation. CRP was measured the following morning, and plasma IL-6 levels from 111 randomly selected children were also examined. Plasma CRP and IL-6 levels were elevated in children with SDB. Log plasma CRP levels were higher in the moderate-severe SDB group (apnea/hypopnea index, AHI ≥ 5) compared to the mild SDB group (AHI ≥ 1 and <5; p < 0.0001) or the control group (AHI < 1; p = 0.0001). Log plasma CRP levels correlated with AHI, arousal index, relative BMI, and SpO₂ nadir (r = 0.30, p < 0.0001; r = 0.21, p = 0.002; r = 0.39, p < 0.0001, r = −0.36, p < 0.0001, respectively). Log plasma CRP levels were lower in children with SpO₂ nadir ≥90 (p < 0.0001). Sub-analysis of the 116 non-obese children in the cohort revealed similar findings. Log plasma IL-6 levels were increased in children with moderate–severe SDB compared to controls (p = 0.03) and correlated with AHI (r = 0.28, p = 0.003) and SpO₂ nadir (r = −0.24, p = 0.02). Children with SDB display significant severity-dependent increases in plasma CRP and IL-6 levels independent of obesity.     

Saliva Interleukin-6 in patients with inflammatory bowel disease

Objective. The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions that affect the gastrointestinal tract. In regulation of this inflammatory process, Interleukin-6 (IL-6) has a major role. Overproduction of IL-6 by immunocompetent cells contributes to development of the inflammatory condition. Elevated levels of IL-6 in saliva could be expected, because the saliva-producing cells are part of the digestive system. Material and methods. IL-6 concentrations in saliva and plasma were studied in patients with CD (n=15), UC (n=7) and reference persons (RP) (n=19) by use of an ELISA method. Results. A significant difference in saliva IL-6 concentration between CD patients (median 16.9 ng/L; p<0.05) and RP (median 6.3 ng/L) was found. A significant difference in plasma IL-6 concentration between CD (median 10.3 ng/L; p<0.001) or UC (median 7.8 ng/L; p<0.001) and RP (median 0.8 ng/L) was observed. In patients with CD, plasma IL-6 correlated significantly with C-reactive protein (CRP) as well as albumin. In patients with UC, saliva IL-6 and plasma IL-6 correlated significantly with AI (activity index) scores as well as albumin. In patients with UC, a significant correlation between the saliva and plasma IL-6 concentrations was found. Conclusions. IL-6 was found in saliva in patients with IBD, documenting the general involvement of the gastrointestinal tract extending to the mouth cavity, and measuring IL-6 may be an additional method for evaluating and monitoring the disease activity.     

An experimental study on ulcerative colitis as a potential target for probiotic therapy by Lactobacillus acidophilus with or without “olsalazine”

Traditional medical treatments for ulcerative colitis (UC) are still compromised by its adverse effects and not potent enough to keep in remission for long-term periods. So, new therapies that are targeted at specific disease mechanisms have the potential to provide more effective and safe treatments for ulcerative colitis. Probiotics is recently introduced as a therapy for ulcerative colitis. In the present study, Lactobacillus acidophilus was selected as a probiotic therapy to investigate its effects in oxazolone-induced colitis model in rats that mimics the picture in human. The rats were grouped (8 rats each) as normal control group (Group I), Group II served as untreated oxazolone-induced colitis, Group III oxazolone-induced colitis treated with probiotic L. acidophilus (1 × 10⁷ colony-forming units (CFU)/mL/day oral for 14 days), Group IV oxazolone-induced colitis treated with olsalazine (60 mg/kg/day oral for 14 days), Group V oxazolone-induced colitis treated with probiotic L. acidophilus and olsalazine in the same doses and duration. Disease activity index (DAI) was recorded, serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and intrleukin-6 (IL-6) was assessed as inflammatory markers and the histopathological picture of the colon of each rat was studied. Disease activity index (DAI) showed significant positive correlation with the elevated serum levels of CRP (r = 0.741, p < 0.05), TNF-α (r = 0.802, p < 0.05) and IL-6 (r = 0.801, p < 0.05). Treatment with either L. acidophilus (group III) or olsalazine (group IV) resulted in significant reduction in serum levels of CRP, TNF-α and IL-6, as well as disease activity index (DAI). Treatment with combination of L. acidophilus and olsalazine (group V) offered more significant reduction in serum levels of CRP, TNF-α, IL-6 and disease activity index (DAI) when compared to either group II (untreated group), group III (treated with L. acidophilus) or group IV (treated with olsalazine). So, it was concluded that L. acidophilus probiotic could be recommended as adjuvant therapy in combination with olsalazine to achieve more effective treatment for ulcerative colitis. For application in human, this needs to be verified in further clinical studies.     

CD99 refers to the activity of inflammatory bowel disease

Background: Inflammatory bowel disease (IBD), composed of Crohn’s disease (CD) and ulcerative colitis (UC), is an inflammatory autoimmune disease. CD99 has been reported to participate in migration of leukocytes and T cell activation. However, the roles of CD99 in IBD are obscure.

Materials and methods: CD99 expression was examined in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa from IBD patients by qRT-PCR. Serum TNF-α and IL-17A levels were detected by ELISA. Correlations of CD99 expression with TNF-α, IL-17A, Crohn’s disease activity index (CDAI), simple endoscopic score for CD (SES-CD), Mayo index, and Truelove grading were performed by Pearson’s correlation.

Results: CD99 expression was increased in PBMCs and inflamed mucosa from active CD and UC patients, and CD99 expression was also increased in the inflamed mucosa compared with unaffected control from the same patients. Serum TNF-α and IL-17A levels were increased in active CD or UC patients, and positively correlated with CD99 expression in PBMCs (CD: r?=?.402, p?=?.009; r?=?.350, p?=?.025. UC: r?=?.289, p?=?.028; r?=?.322, p?=?.014). Moreover, CD99 expression in inflamed mucosa was correlated with CDAI, SES-CD, Mayo index, and Truelove grading (r?=?.410, p?=?.012; r?=?.341, p?=?.005; r?=?.366, p?=?.002; r?=?.312, p?=?.011).

Conclusion: CD99 expression is increased in patients with active IBD, and positively correlated with disease activity. Therefore, CD99 expression can be used as an index to evaluate the activity of IBD.     

Plasma ratio of angiopoietin-2 to angiopoietin-1 is a biomarker of vascular impairment in chronic obstructive pulmonary disease patients

Chronic obstructive pulmonary disease (COPD) patients have an increased risk of cardiovascular disease. Muscle biopsies have revealed that the muscle vasculature in COPD patients was characterized by a capillary rarefaction with reduced pericyte coverage. Thus, an imbalance of the plasma Angiopoietin-1 / Angiopoietin-2 (Ang2/Ang1) ratio could constitute a non-invasive marker of the muscle vascular impairment. In 14 COPD patients (65.5±5.1-year-old) and 7 HC (63.3±5.8-year-old), plasma samples were obtained at 3 time-points: before, after 5 weeks (W5), and after 10 weeks (W10) of exercise training. COPD patients showed a muscle capillary rarefaction at baseline with a reduced capillary coverage at W5 and W10. The plasma Ang2/Ang1 ratio was significantly higher in COPD patients vs. HC during the training (Group: p=0.01). The plasma Ang2/Ang1 ratio was inversely correlated with the pericyte coverage index regardless of the time period W0 (r=?0.51; p=0.02), W5 (r=?0.48; p=0.04), and W10 (r=?0.61; p<0.01). Last, in ECFC/MSC co-cultures exposed to the W10 serum from COPD patients and HC, the plasma Ang2/Ang1 at W10 were inversely correlated with calponin staining (r=?0.64. p=0.01 and r= 0.71. p<0.01, Fig. 1B), in line with a role of this plasma Ang2/Ang1 in the MSC differentiation into pericytes. Altogether, plasma Ang2/Ang1 ratio could constitute a potential marker of the vascular impairment in COPD patients.

     

Prevalence and predictors of non-alcoholic steatohepatitis in subjects with morbid obesity and with or without type 2 diabetes

AimTo investigate the prevalence of biopsy-proven non-alcoholic steatohepatitis (NASH) in a cohort of patients with morbid obesity and with or without type 2 diabetes (T2D) and to find non-invasive predictors of NASH severity.MethodsWe evaluated a cohort of 412 subjects (age 19–67 years, body mass index-BMI: 44.98 kg/m²), who underwent fine-needle liver biopsy during bariatric surgery. Thirty-six percent of the subjects were affected by T2D. Liver biopsies were classified according to the Kleiner's NAFLD Activity Score (NAS). NAFLD Fibrosis Score (NFS), AST/ALT ratio, AST to Platelet ratio (APRI), fibrosis-4 score (FIB4) were calculated. A neural network analysis (NNA) was run to predict NASH severity.ResultsThe prevalence of biopsy-proven NASH was 63% and 78% in subjects with obesity and without or with T2D, respectively. T2D doubled the risk of NASH [OR 2.079 (95% IC=1.31–3.29)]. The prevalence of NAFL increased with the increase of BMI, while there was an inverse correlation between BMI and NASH (r=?0.145 p=0.003). Only mild liver fibrosis was observed. HOMA-IR was positively associated with hepatocyte ballooning (r=0.208, p<0.0001) and fibrosis (r=0.159, p=0.008). The NNA highlighted a specificity of 77.3% using HDL-cholesterol, BMI, and HOMA-IR as main determinants of NASH.ConclusionsOur data show a higher prevalence of NASH in patients with morbid obesity than reported in the literature and the pivotal role of T2D among the risk factors for NASH development. However, the inverse correlation observed between BMI and biopsy-proven NASH suggests that over a certain threshold adiposity can be somewhat protective against liver damage. Our model predicts NASH presence with high specificity, thus helping identifying subjects who should promptly undergo liver biopsy.     

Lipoprotein lipase in relation to inflammatory activity in rheumatoid arthritis

Objective. To evaluate the impact of chronic inflammation on lipoprotein lipase (LPL) levels and triglyceride metabolism in patients with rheumatoid arthritis (RA). Design. Plasma levels of LPL activity and mass before and after heparin were determined in post-menopausal women with active RA and in controls. The results were related to lipid levels and inflammatory variables. The LPL activity and mass together with triglyceride levels were also measured before and 6 h after an oral fat load. Setting. The study was performed on in- and out-patients at a University Rheumatology clinic. The controls came from the same reference area. Subjects. Altogether 17 consecutive post-menopausal female patients with RA and 16 age and sex matched controls were enrolled for the initial determination of LPL. Fifteen of the patients and 15 of the controls agreed to take part in the fat load. Of these, one patient and one control were excluded. Main outcome measures. LPL determination: basal levels and post-heparin levels of LPL activity and mass. Correlations between LPL and blood lipids (cholesterol, triglycerides), lipoprotein levels (high density lipoprotein, HDL; low density lipoprotein, LDL), erythrocyte sedimentation rate (ESR) acute phase proteins (orosomucoid, haptoglobin, fibrinogen mass) and cytokines (tumour necrosis factor α, TNF-α; interleukin 1β, IL-1β; and interleukin-6, IL-6). Fat tolerance test: LPL activity, mass and triglyceride levels before and 6 h after a per oral fat load. Results. Pre-heparin LPL mass (P<0.01) and activity (P<0.01) were significantly lower in the rheumatoid patients. Pre-heparin LPL mass showed no correlation to the lipid levels, but an inverse correlation to several inflammatory parameters; it was significant for orosomucoid (r_s=?0.63, P<0.05) and C-reactive protein (CRP) (r_s=?0.54, P<0.05) and close to significant for haptoglobin (r_s=?0.48, P=0.087) and IL-6 (r_s=?0.52, P=0.061). Six hours after a lipid load the LPL activity and mass were significantly lower in RA (P<0.05 and P<0.01, respectively) but the triglyceride level was not significantly different compared to controls. Conclusion. An inverse relationship exists between inflammatory status and pre-heparin LPL mass. Pre-heparin LPL mass reflects mainly the inactive monomeric fraction of LPL. This has been shown to hinder the uptake of remnant lipoprotein particles through competition with lipoprotein bound dimeric LPL for the LDL receptor-related protein (LRP receptor) on hepatocytes and macrophages in culture. A decrease of the level of monomeric LPL in plasma may thus be beneficial for remnant catabolism. The same mechanism may on the other hand increase macrophage uptake of lipids. This may not affect global lipid metabolism but may be important in driving the atherosclerotic process in the vessel wall.     

Does treatment affect the levels of serum Interleukin-6, Interleukin-8 and procalcitonin in diabetic foot infection? A pilot study

AimsTo investigate about serum PCT, IL-6 and IL-8 levels and how they are affected by the treatment in diabetic foot patients.MethodsFifty patients’ blood samples were taken to study ESR and CRP, IL-6, IL-8 and PCT before and at the 14th day of the treatment.ResultsThe pretreatment results of the 50 patients showed positive correlations between PCT and either ESH (r = 0.49, p < 0.001), or CRP (r = 0.56, p < 0.001). Similarly, there was a positive correlation between IL-6 and ESH (r = 0.46, p = 0.001), just like as it was between IL-6 and CRP (r = 0.54, p < 0.001). At the 14th day, the levels of ESR (70 ± 30.2 and 58.4 ± 26.2, p = 0.02), CRP (63.8 ± 73.1 and 18.1 ± 19.7, p < 0.001) and PCT (0.6 ± 2.1 and 0.05 ± 0.02, p = 0.007) were significantly decreased while IL-6 was decreased at a close range to statistical significancy at healing patients (97.5 ± 147.2 and 47.1 ± 77.6; p = 0.05), but they did not at nonhealing patients. IL-8 levels were not changed anyhow.ConclusionsPCT was significantly decreased such as ESR and CRP were in the early phase of healing; IL-6 and IL-8 levels were also decreased by the treatment, but not statistically significantly. IL-6 and PCT were affected in correlation with the other inflammatory parameters in the beginning, but IL-8 was not. PCT and IL-6 may be useful like CRP and ESR in the diagnosis and follow up of diabetic foot infection, but IL-8 is not. Further investigation is needed.     

Serum IL-6 level as a marker of disease activity in ankylosing spondylitis patients with pure axial involvement

BackgroundThe assessment of disease activity in patients with ankylosing spondylitis (AS) continues to be a challenging issue. The currently available markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) show poor correlation with clinical disease activity.ObjectivesTo compare serum IL-6 and hs-CRP levels between patients with AS with pure axial involvement and healthy controls; and to correlate them with Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI) and Bath ankylosing spondylitis metrology index (BASMI).MethodsSixty-two consecutive patients of AS with pure axial involvement satisfying the modified New York criteria and 60 age-matched healthy controls were recruited. In all patients, Bath indices were measured and fasting venous blood samples for serum IL-6 and hs-CRP levels were obtained. Comparison of median of serum IL-6 and hs-CRP levels was done between cases and healthy controls and levels also correlated with Bath indices by appropriate statistical methods.ResultsThe median serum IL-6 and hs-CRP levels were significantly higher in cases as compared to healthy controls (p = 0.001). Serum IL-6 levels correlated significantly with BASDAI and BASFI (r = 0.61, p = 0.001 and r = 0.27, p = 0.032 respectively) but no correlation was found with BASMI (r = −0.08, p = 0.53). Serum hs-CRP did not correlate with Bath indices except BASMI (r = 0.28, p = 0.03).ConclusionSerum IL-6 levels can be reliably used as an aid in monitoring of disease activity in AS patients with pure axial involvement.     

Trans-Myocardial Blood Interleukin-6 Levels Relate to Intracoronary Imaging-Defined Features of Plaque Vulnerability and Predict Procedure-Induced Myocardial Infarction

BackgroundIntravascular imaging has defined various vulnerable plaque (VP) phenotypes that predict future clinical events. Atherosclerosis is an inflammatory process and inflammation, measured by systemic biomarkers can also predict events and anti-inflammatory therapy is beneficial. We were interested to assess the relationship between plaque phenotypes and key inflammatory biomarkers, measured close to the coronary.MethodsNinety-two patients scheduled for elective percutaneous coronary intervention (PCI) underwent virtual histology intravascular ultrasound, optical coherence tomography, pressure wire and blood sampling from the guide catheter (GC), coronary sinus (CS) to determine trans-myocardial gradient (TMG = CS-GC) and from peripheral blood. Procedure related troponin release was assessed at 6-hours post-PCI from peripheral venous blood. Biomarker data were analysed and compared with coronary data.ResultsInterleukin (IL)-6 was associated with increased levels of tumour necrosis factor (TNF)-α and C-reactive protein (CRP) and the pre-PCI IL-6 TMG correlated with plaque features of vulnerability: plaque burden - PB (r = 0.253, p = 0.04) and minimal lumen area - MLA (r = −0.438, p = 0.007), although no relationship existed for thin-capped fibroatheroma defined by either imaging modality. Peripheral IL-6 levels had no correlation with post PCI troponin, although the pre-PCI IL-6 TMG was related (r = 0.334, p = 0.006), as was PB (r = 0.27, p = 0.029).ConclusionIL-6 TMG pre-PCI correlates with plaque burden and MLA that have been shown to predict future clinical events and is correlated with post-PCI troponin release. These associations were not apparent from peripheral blood and suggest that local coronary biomarker signatures may help further define vulnerability and risk.     

Effect of metformin and sulfonylurea on C-reactive protein level in well-controlled type 2 diabetics with metabolic syndrome

The objective of this study was to examine the effect of the antihyperglycemic agents metformin (insulin sensitizer) and glibenclamide (insulin secretory agent) on the serum level of C-reactive protein (CRP) in well-controlled type 2 diabetics with metabolic syndrome. The participants were diabetic patients being followed in the medical outpatient clinic of King Abdulaziz University Hospital. The inclusion criteria were type 2 diabetics with the metabolic syndrome, well-controlled blood glucose on metformin alone or glibenclamide alone, and exclusion of major medical illness. Patients were divided into two groups according to the antihyperglycemic agent used. CRP level was measured 4-wk apart and the mean was calculated. The following data were collected from the study groups: age, sex, body mass index (BMI), duration of diabetes, smoking history, presence of hypertension, hyperlipidemia, and mean CRP level. A total of 110 patients were studied, 65 using metformin and 45 using glibenclamide. CRP level was significantly lower in patients using metformin for blood glucose control compared with those using glibenclamide, 5.56 and 8.3 mg/L, respectively (p=0.01). A significantly higher level was observed in hypertensive and hyperlipidemic patients compared with normotensive and normolipidemic, 5.3 vs 3.2 mg/L and 7.1 vs 4.3 mg/L, respectively (p=0.02, 0.01). There was a statistically significant correlation between CRP and BMI (r=0.37) and age (r=0.36) (all p=0.01). The data showed that metformin decreases the level of circulating CRP, a marker of inflammation, more than glibenclamide.     

Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability

A chronic (auto)immune response is the critical mechanism in atherosclerosis. Interleukin-17A is a pivotal effector cytokine, which modulates immune cell trafficking and initiates inflammation in (auto)immune and infectious diseases. However, expression of IL-17A in the context of human atherosclerosis has hardly been explored. Carotid artery plaques were collected from 79 patients undergoing endarterectomy. Patients were grouped according to their symptomatic status (TIA, stroke), plaque morphology and medication. Quantitative RT-PCR was used to analyze tissue inflammation and immunohistochemistry to assess cellular source of IL-17A expression and lesion morphology. Carotid plaques from patients with ischemic symptoms were characterized by a highly activated inflammatory milieu including accumulation of T cells (p = 0.04) and expression of IL-6 and VCAM1 (p = 0.02, 0.01). Expression of IL-17A and its positive regulators IL-21 and IL-23 was present in atherosclerotic lesions, significantly upregulated in atheromas of symptomatic patients (p = 0.005, 0.004, 0.03), and expression of IL-17A and IL-21 showed a strong correlation (p = 0.002, r = 0.52). The cellular sources of lesional IL-17A expression are T cells, macrophages, B cells and plasma cells. Vulnerable/ruptured (complicated) plaques were significantly associated with IL-17A expression levels (p = 0.003). In addition, IL-17A showed a marked negative correlation with the potent anti-inflammatory/atheroprotective cytokine IL-10 (p = 0.0006, r = −0.46). Furthermore, treatment with a HMG-CoA reductase inhibitor or acetylsalicylic acid showed reduced levels of IL-21, IL-23 and VCAM1 (all p < 0.05), but did not influence IL-17A. The association of IL-17A with ischemic symptoms and vulnerable plaque characteristics suggests that the pro-inflammatory cytokine IL-17A may contribute to atherosclerosis und plaque instability.     

CECDAIic – a new useful tool in pan-intestinal evaluation of Crohn’s disease patients in the era of mucosal healing

Abstract

Background: Pan-intestinal capsule endoscopy (Pan-CE) has been used to assess both the small and large bowel inflammation in Crohn’s disease (CD) patients in a single examination. The capsule endoscopy Crohn’s disease activity index (CECDAI) was initially developed to measure mucosal disease activity in the small bowel, although in 2018, it was extended to the colon for standardization of inflammatory activity (CECDAIic). The aim of this study was to apply the CECDAIic in a cohort of CD patients that underwent Pan-CE to evaluate the inter-observer agreement and the correlation between this score and inflammatory parameters.

Methods: The videos were read and scored using the CECDAIic by three independent experienced operators, blinded to the results of the standard workup. Statistical analysis was performed with SPSS^®, using Kendall’s coefficient to evaluate the inter-observer agreement. Spearman correlation (r_s) was used to access the correlation between the score and inflammatory biomarkers.

Results: Included 22 patients, 59.1% males with mean age of 30.7?±?11.1 years. The median CECDAIic score was 9.17 (0–37). The overall CECDAIic score Kendall coefficient was 0.94, demonstrating a statistically significant (p?<?.001) and excellent agreement between the three observers. In addition, we found a very good correlation between CECDAIic and calprotectin (r_s?=?0.82; p?=?.012) and a moderate correlation with C-reactive protein (CRP, r_s?=?0.50; p?=?.019).

Conclusions: CECDAIic is a new score with excellent inter-observer agreement and strong correlation with calprotectin levels.     

Gender specific associations between matrix metalloproteinases and inflammatory markers in post myocardial infarction patients

ObjectiveAtherothrombotic disease in the coronary arteries leads to myocardial infarction (MI) through plaque rupture or erosion of the endothelium, the former mechanism predominating in men and the latter in women. Inflammation is a key feature of these processes, and the interplay between inflammation and matrix metalloproteinases (MMPs) in this context is not fully understood. In this study, we investigated the association between inflammatory markers and MMPs in men and women.MethodsBlood samples were drawn 3 months after a first MI in 387 patients and 387 sex- and age-matched controls (82% men). C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, -18, tumour necrosis factor-α (TNF-α), macrophage chemoattractant protein-1 (MCP-1), MMP-1, -3 and -9 were measured. Coronary angiography was performed in 243 of the patients, and they were classified into 0-, 1-, 2- or 3-vessel disease groups.ResultsCRP, IL-6, -8, -18 and TNF-α were higher, and MMP-3 and -9 were lower, in patients than in controls. A greater proportion of women (49%) had 0-vessel disease than men (16%, p < 0.0001). A gender specific pattern of associations between inflammatory markers and MMPs was found as IL-6 (r_S = 0.29, p < 0.05), IL-18 (r_S = 0.34, p < 0.01) and MCP-1 (r_S = 0.35, p < 0.01) correlated with MMP-3 in female patients, whereas CRP (r_S = 0.23, p < 0.0001), IL-6 (r_S = 0.13, p < 0.05) and IL-8 (r_S = ?0.21, p < 0.01) correlated with MMP-9 in male patients.ConclusionsThe present study demonstrates different patterns of association between inflammatory markers and MMPs in men and women, strengthening the hypothesis of gender specific differences in pathophysiological mechanisms of MI.     

Collagenase-3 (MMP-13) expression by inflamed mucosa in inflammatory bowel disease

Objective. To determine whether the expression of collagenase-3 (MMP-13) in biopsies from patients with inflammatory bowel disease is correlated with histological inflammation parameters. Material and methods. Fifty-nine patients with inflammatory bowel disease were included in the study. The control group comprised 20 patients free of inflammatory disease and ten patients with acute diverticulitis. MMP-13 expression was determined by immunohistochemical staining and the specimens were assigned a histological inflammation score. Results. It was found that 62.8% of patients with ulcerative colitis (UC) and 54.1% of patients with Crohn's disease (CD) showed MMP-13-positive immunostaining in biopsies from affected areas. MMP-13-positive staining was more intense in ulcerated colonic mucosa. A positive and significant correlation was found between MMP-13 expression and the histological inflammation scores in mucosal samples from patients with CD (r=0.74, p<0.0001) or UC (r=0.62, p<0.0001). However, no MMP-13-positive immunostaining was found in either the biopsy specimens of the control group or those biopsies taken from patients with UC or CD in microscopically confirmed non-affected areas of the colonic mucosa. Similarly, colonic mucosa samples of the 10 patients with acute diverticulitis did not show immunostaining for MMP-13. Conclusions. Our findings demonstrating the absence of MMP-13 expression in non-inflamed colonic mucosa or in acute diverticulitis, as well as a positive correlation between elevated MMP-13 expression and histological criteria of inflammation in patients with inflammatory bowel diseases (CD and UC) suggest a role of the protease in the pathogenesis of these latter processes.     

C-reactive protein is directly related to plasminogen activator inhibitor type 1 (PAI-1) levels in diabetic subjects with the 4G allele at position -675 of the PAI-1 gene

Background and aimsC-reactive protein (CRP) has been identified as a possible factor able to promote atherosclerosis. “In vitro” studies have demonstrated that CRP induces plasminogen activator inhibitor type 1 (PAI-1) expression, suggesting a hypofibrinolytic role for CRP. As CRP and PAI-1 levels increase in type 2 diabetic subjects, we decided to study the relationship between CRP and PAI-1, and the role of the 4G/5G polymorphism of the PAI-1 gene on this relationship in a diabetic population without complications.Methods and resultsTwo hundred and ninety-five type 2 diabetic patients (age 60.9 ± 10.5 years) and 290 healthy controls (age 59.2 ± 11.5 years) were enrolled. A significant correlation between PAI-1 and CRP in diabetic subjects was found (r = 0.45, p < 0.001), whereas no relationship was evident in the control subjects between these inflammatory markers. Multiple regression analysis highlighted that CRP is the only one significant variable of PAI-1 antigen in diabetic subjects (partial r = 0.31, p < 0.01). Stratifying by genotype, a positive correlation between PAI-1 and CRP in 4G/4G (partial r = 0.64 p < 0.001) and 4G/5G (partial r = 0.47, p < 0.001) subjects was found, whereas no correlation in 5G/5G was present. Multiple regression analysis confirmed the presence of this correlation in 4G/4G (partial r = 0.45, p < 0.001) and in 4G/5G (partial r = 0.34, p = 0.007) diabetic patients.ConclusionsThese findings demonstrate that CRP plays an important role in the complex mechanism regulating PAI-1 antigen in 4G diabetic carriers.