Significance of plasma osteopontin in diagnosis of hepatitis C virus-related hepatocellular carcinoma

Background and study aimsAlfa fetoprotein (AFP) is widely used as a surveillance test for hepatocellular carcinoma (HCC) among patients with liver cirrhosis (LC). However, the clinical use of AFP has been shown to present some important limitations in sensitivity and specificity. Osteopontin (OPN) is a secreted matrix glycoprotein that is emerging as a significant protein in the biology of HCC. The aim of this study was to assess the diagnostic value of plasma OPN compared with that of AFP in the diagnosis of HCC among hepatitis C virus (HCV)-related LC.Patients and methodsPlasma levels of OPN and AFP were measured in 69 Egyptian patients with HCV-related LC (35 with HCC and 34 without HCC) and 20 healthy controls.ResultsBoth median AFP and OPN levels were significantly higher in the HCC group compared to LC and healthy control groups (p < 0.001 in each) and in LC compared to the control group (p < 0.001). In the HCC group, both OPN and AFP levels were significantly higher in patients with Child–Pugh class C and B compared to class A (p < 0.05 in each). There was no correlation between OPN and AFP levels. The OPN level was significantly higher in patients with multiple focal lesions than in those with single lesions (p < 0.05) and in patients with portal vein invasion compared to patients without portal vein invasion (p < 0.05). Receiver operator characteristic (ROC) curves showed that the area under the curve (AUC) for OPN and AFP was 0.824 and 0.730, respectively.ConclusionOPN is a promising tumour marker which could be used as a screening test for the diagnosis of HCC in patients with LC and, hence, improves the prognosis and survival rate of these patients. The association of OPN with the multiplicity of focal lesions and portal vein invasion suggests an additional prognostic value.     

Elevated level of serum osteopontin in school-age children with asthma

BackgroundThe role of osteopontin (OPN) has not been elucidated in childhood asthma.ObjectiveOur purpose was to investigate whether OPN levels change due to allergic inflammation in pre-school and school-age children.MethodsIn this prospective, cross-sectional study, 42 healthy children and a total of 51 children with asthma were recruited. OPN levels and its association with clinical and laboratory parameters were investigated in the study population. The asthma group were divided into two groups with respect to age, ≤5-years (n = 23) and >5-years (n = 28), and labelled Asthma Group 1 and Asthma Group 2, respectively. OPN levels were compared between subgroups.ResultsSerum OPN levels were significantly higher in the asthma group when compared to the control group (p = 0.004). OPN levels were similar in Asthma Group 1 and control groups, whereas it was found to be higher in Asthma Group 2 (p > 0.025, p = 0.001, respectively). In the >5-years age asthmatic group, OPN levels of the patients with allergic rhinitis (n = 15) were higher than those of the patients (n = 13) without allergic rhinitis (p = 0.021).ConclusionThe study underscores the relationship between childhood asthma and OPN as the first study in the literature. In this study we found that OPN, which plays a role in Th2 mediated inflammation, may also play a role in childhood asthma. The fact that OPN levels do not increase in preschool-age children with asthma might be due to the transient wheezing in this group.     

Increased level of resistin predicts development of atrial fibrillation

BackgroundResistin is a peptide hormone that is secreted from lipid cells and is linked to type-2 diabetes, obesity, and inflammation. Being an important adipocytokine, resistin was proven to play an important role in cardiovascular disease. We compared resistin levels in patients with and without atrial fibrillation (AF) to demonstrate the relationship between plasma resistin levels and AF.MethodOne hundred patients with AF and 58 control patients who were matched in terms of age, gender, and risk factors were included in the trial. Their clinical risk factors, biometric measurements, echocardiographic work up, biochemical parameters including resistin and high-sensitivity C-reactive protein (hs-CRP) levels were compared.ResultsIn patients with AF, plasma resistin levels (7.34 ± 1.63 ng/mL vs 6.67 ± 1.14 ng/mL; p = 0.003) and hs-CRP levels (3.01 ± 1.54 mg/L vs 2.16 ± 1.28 mg/L; p = 0.001) were higher than control group. In subgroup analysis, resistin levels were significantly higher in patients with paroxysmal (7.59 ± 1.57 ng/mL; p = 0.032) and persistent AF (7.73 ± 1.60 ng/mL; p = 0.006), but not in patients with permanent AF subgroups (6.86 ± 1.61 ng/mL; p = 0.92) compared to controls. However, hs-CRP levels were significantly higher only in permanent AF patients compared to control group (3.26 ± 1.46 mg/L vs 2.16 ± 1.28 mg/L; p = 0.02). In multivariate regression analysis using model adjusted for age, gender, body mas index, hypertension, diabetes mellitus, and creatinine levels, plasma resistin levels [odds ratio (OR): 1.30; 95% confidence interval (CI): 1.01–1.70; p = 0.04] and hs-CRP levels (OR: 1.44; 95% CI: 1.12–1.86; p = 0.004) were the only independent predictors of AF.ConclusionThe elevated levels of plasma resistin were related to paroxysmal AF group and persistent AF group, but not to permanent AF group.     

Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in rheumatoid arthritis patients: Correlation with serum osteopontin levels and disease activity

BackgroundRheumatoid arthritis (RA) is a systemic, chronic inflammatory disease with genetic predisposition. Osteopontin (OPN) is overexpressed in RA and plays a key role in the perpetuation of synovitis. Not all RA patients show the same level of response to methotrexate (MTX) suggesting genetic variations in the drug-metabolizing enzymes.Aim of the workTo detect methylene-tetra-hydrofolate reductase (MTHFR) 677C/T and 1298A/C gene polymorphisms in RA patients treated with MTX and to investigate the relationship with serum OPN levels and disease activity.Patients and methods62 RA patients and 21 healthy controls were included. Serum OPN was measured using ELISA. Genotyping of MTHFR gene was carried out by polymerase chain reaction-restriction fragment length polymorphism. Disease activity score in 28 joints (DAS28) and the modified health assessment questionnaire (MHAQ) were assessed.ResultsThe patients’ age was 42.7 ± 12.7 years, F:M (4.6:1) and a disease duration of 5.7 ± 4.6 years. Their DAS28 was 4.1 ± 1.6 and the MHAQ (median 1; range 0–2.3). Serum OPN levels in RA patients (median 8.8; range 4–44.5 ng/ml) were significantly higher than in control (5.6; 2.1–10.9) (p = 0.002). In RA patients, serum OPN significantly correlated with the duration of morning stiffness (p = 0.009), ESR (p < 0.0001) and DAS28 (p < 0.0001). MTHFR (677C>T) polymorphisms significantly correlated with MHAQ (p = 0.012) while (1298A>C) polymorphisms significantly correlated with tender joint count (p = 0.04). OPN levels were higher among patients with MTHFR (1298A/C) AC genotype (8.9; 4.1–33.9 ng/ml), while in those with (677C>T) polymorphisms it was higher among those with CT genotype (8.9; 4.1–44.5).ConclusionSerum OPN level relates with the degree of rheumatoid activity.     

Bile acid malabsorption assessed by 7 alpha-hydroxy-4-cholesten-3-one in pediatric inflammatory bowel disease: Correlation to clinical and laboratory findings

Background and aimsMeasurement of 7 alpha-hydroxy-4-cholesten-3-one (C4) in serum is a semiquantitative test for bile acid malabsorption (BAM). We have previously established pediatric normal values for C4 with an upper limit of normal of 66.5 ng/mL, independent of age and sex. Here we performed the C4 test in 58 pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC).MethodsC4 was measured using high performance liquid chromatography (HPLC) in fasting serum samples of 44 patients with CD (range 7–19 years) and 14 with UC (4–18 years). Disease activity was assessed by the pediatric CD and UC activity indices (PCDAI and PUCAI, respectively) plus serum (CRP, ESR) and fecal inflammatory markers (calprotectin).ResultsC4 concentrations were increased in 10 CD (23%) (range: 70.8–269.3 ng/mL) but only one UC patient (72.9 ng/mL). CD patients with diarrhea (n = 12) had higher C4-values compared to those without (76.9 vs. 30.4 ng/mL; p = 0.0043). Ileal resection in CD patients (n = 10) was associated with increased C4 concentrations (81.2 vs. 24.3 ng/mL, p = 0.0004). No correlation was found between C4 values and inflammatory markers. Six of 7 CD patients with persistent diarrhea but quiescent disease (PCDAI ≤ 12.5) had C4 values indicating BAM.ConclusionElevated C4 concentrations indicating BAM are common in children with CD. They are associated with ileal resection and non-bloody diarrhea in the absence of active disease or elevated inflammatory markers. The C4-test identifies a subgroup of CD patients with persistent diarrhea in spite of clinical remission which may benefit from bile acid binding therapy.     

Low levels of vitamin D are common in patients with ileal pouches irrespective of pouch inflammation

BackgroundVitamin D (25(OH) D3) levels in pouch patients are not well defined.AimTo evaluate the frequency and factors associated with low 25(OH) D3 levels in pouch patients with underlying inflammatory bowel disease (IBD).MethodsA consecutive of 157 pouch patients was identified from our Pouchitis Registry. A sample of 155 ulcerative colitis (UC) patients without IPAA served as controls.ResultsThe mean age of the cohort was 37.5 ± 14.2 years, with 86 (54.8%) being female. Low 25(OH)D3 levels (< 31 ng/mL) were detected in 69.4% of patients (N = 109). 34 (21.7%) of the 157 patients examined were 25(OH)D3 deficient (< 20 ng/mL). This was higher than the frequency of vitamin D insufficiency or deficiency in a sample of UC patients without IPAA. Between patients with and without normal 25(OH) D3 levels (> 31 ng/mL), no differences were identified in terms of demographic, pouch, and medication variables. A low hemoglobin level was found to be associated with low 25(OH) D3 levels in both univariate (p = 0.02) and multivariate analyses (odds ratio [OR] = 3.37; 95% confidence interval [CI]: 1.41–8.06; p = 0.01). Low levels of 25(OH)D3 was not related to markers of pouch inflammation, in particular there was no relation to pouchitis (OR = 1.20; 95% CI: 0.41–3.52; p = 0.74).ConclusionLow 25(OH)D3 level was common in this cohort, irrespective of inflammation of the pouch, possibly suggesting a strategy of routine testing in this population. Anemia was found to be associated with a low 25(OH)D3 level.     

Radical cystectomy versus organ-sparing trimodality treatment in muscle-invasive bladder cancer: A systematic review of clinical trials

BackgroundRadical cystectomy (RC) represents the mainstay of treatment in patients with muscle-invasive urinary bladder cancer but how it compares with the best organ preservation approach is not known.Materials and methodsThe objective of our review is to compare the 5-year overall survival (OS) rates from retrospective and prospective studies of RC and trimodality treatment (TMT), i.e. concurrent delivery of chemotherapy and radiotherapy after a transurethral resection of bladder tumor (TURBT), involving a total of 10,265 and 3131 patients, respectively. We used random-effect models to pool outcomes across studies and compared event rates of combined outcomes for TMT and RC using an interaction test.ResultsThe median 5-year OS rate was 57% in the TMT group, when compared with 52% (P = 0.04), 51% (P = 0.02) and 53% (P = 0.38) in the whole group receiving RC or the group treated with RC alone or RC + chemotherapy, respectively. The hazard risk (HR) of mortality of patients treated with TMT or RC was 1.22 (95% CI = 1.13–1.32) with an absolute benefit of 5% in favor of the former. The HR of mortality from TMT persisted significantly better not only versus the group treated with RC alone (HR = 1.22; 95% CI = 1.12–1.32), but also versus the group receiving RC + chemotherapy (HR = 1.22; 95% CI = 1.09–1.36). Multivariate analysis confirmed TMT as a significant prognostic variable for both RC alone and RC + chemotherapy.ConclusionCompared with RC, TMT seems to be associated with a better outcome for patients with muscle-invasive bladder cancer (MIBC). The addition of chemotherapy may improve the RC outcome in some subgroups of patients with a higher probability of micrometastases. Prospective randomized trials are urged to verify these findings and better define the role of organ preservation and radical treatment strategy in the management of patients with MIBC.     

Plasma and synovial fluid osteopontin levels in patients with knee osteoarthritis: Relation to radiological grade

Aim of workTo investigate osteopontin (OPN) levels in both plasma and synovial fluid of patients with primary knee osteoarthritis (OA) and their relationship with radiological grade.Patient and methodsSixty patients had knee OA and 30 control subjects were included. Anteroposterior knee radiographs were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed by using the Kellgren–Lawrence grading. Osteopontin levels in the plasma and synovial fluid were measured using enzyme-linked immunosorbent assay and compared.ResultsOA patients had higher plasma osteopontin concentrations compared to healthy controls (p < 0.000). Osteopontin levels in synovial fluid were significantly higher with respect to plasma sample (r = 0.694, p < 0.000). The mean plasma levels of osteopontin in KL grade 4 were greater than those in KL grade 3, and the difference was statistically significant (p < 0.01). The plasma osteopontin levels significantly correlated with the severity of disease (r = 0.870, p < 0.000). The synovial fluid levels of osteopontin also correlated with disease severity as regarding the radiological grade (r = 0.817, p < 0.000).ConclusionOsteopontin in plasma and synovial fluid is related to progressive joint damage in knee OA. Osteopontin may serve as a biochemical marker for determining disease severity as regarding radiological grade.     

Altered mRNA expression of telomere binding proteins (TPP1, POT1, RAP1, TRF1 and TRF2) in ulcerative colitis and Crohn's disease

AimsTo determine mRNA expression of telomeric binding proteins in inflammatory bowel disease (IBD), and to note any effects of pharmacotherapy on telomere binding protein expression.MethodsPeripheral blood mononuclear cells (PBMC) obtained from 31 IBD patients and 13 controls were activated with phytohaemagglutinin and purified to yield activated (CD25+) T lymphocytes. TPP1, POT1, RAP1, TRF1 and TRF2 mRNA expression in PBMC and activated T lymphocytes was measured with RT-PCR.ResultsIn activated (CD25+) T lymphocytes, mean TRF2 mRNA levels were lower in both UC (6.6 vs 10, p = 0.004) and CD subjects (6.9 vs 10; p = 0.004). Similarly. in activated (CD25+) T lymphocytes mean RAP1 mRNA expression was significantly lower in UC subjects (4.5 vs 9.8, p = 0.029) but not in CD subjects. In resting PBMC, mean TRF1 mRNA levels were lower in both UC (2.6 vs 3.5; p = 0.008) and CD subjects (1.0 vs 3.5; p = 0.04). No difference in PBMC and activated (CD25+) T lymphocytes mRNA levels of TPP1 and POT1 were noted in either UC or CD subjects. An association with 5-aminosalicylate therapy (R² = 0.4) was only detected with RAP1 mRNA expression. TRF2 mRNA expression was inversely associated with disease duration only in UC subjects (p = 0.05; R² = −0.6).ConclusionsThe downregulation of TRF2 and RAP1 mRNA expression in CD25+ T-lymphocytes in IBD suggests that these telomere binding proteins play a role in telomere regulation and may contribute to the telomeric fusions and chromosomal abnormalities observed in UC. These findings may also indicate a systemic process of telomere uncapping which could represent a biomarker for IBD associated cancer risk.     

Serum vitamin B12 and folate status in patients with inflammatory bowel diseases

BackgroundThe aims of this study were to investigate the prevalence of serum vitamin B₁₂ and folate abnormalities in patients with inflammatory bowel diseases (IBD) and to identify risk factors associated with B₁₂ and folate abnormalities in this entity.Methods138 patients with IBD (45 Crohn's disease and 93 ulcerative colitis) and 53 healthy subjects were enrolled into the study. Fasting serum B₁₂ and folic acid levels were measured and clinical data regarding inflammatory bowel diseases were gathered.ResultsWhile the mean serum B₁₂ concentration in CD patients was 281 ± 166 pg/ml, the mean serum vitamin B₁₂ concentration in UC patients was 348 ± 218 pg/ml (p = 0.224). The number of patients with vitamin B₁₂ deficiency in the CD group was greater than the number of patients with UC [n = 10 (22%) vs. n = 4 (7.5%), p = 0.014]. The number of patients (n = 10, 22%) with B₁₂ deficiency in the CD group was also greater than controls (n = 4, 7.5%) (p = 0.039). With regard to folate levels, the median serum folate level was 7.7 ± 5.3 ng/ml in CD patients, 8.6 ± 8.3 ng/ml in UC patients and 9.9 ± 3.3 ng/ml in the control group (p = n.s.). Patients with a prior ileocolonic resection had an abnormal B₁₂ concentration compared to patients without surgery (p = 0.008). In CD patients, ileal involvement was the only independent risk factor for having a low folate level.ConclusionSerum vitamin B₁₂ and folate deficiencies are common in patients with CD compared to UC patients and controls. In CD patients, prior small intestinal surgery is an independent risk factor for having a low serum vitamin B₁₂ level.     

Evaluation of trefoil factor 3 as a non-invasive biomarker of gastric intestinal metaplasia and gastric cancer in a high-risk population

BackgroundAdenocarcinoma is preceded by chronic atrophic gastritis, gastric intestinal metaplasia and dysplasia. Trefoil factor 3 (TFF3) is a peptide secreted by goblet cells, which is abundantly present in intestinal metaplasia.AimTo evaluate the utility of serum TFF3 as a non-invasive biomarker for the diagnosis of intestinal metaplasia and gastric cancer.MethodsSingle-center, cross-sectional study of 274 patients who consecutively underwent upper gastrointestinal endoscopy with gastric biopsies (updated Sydney system). TFF3 levels were measured in serum by a commercial ELISA kit. Patients with normal histology or chronic atrophic gastritis without intestinal metaplasia comprised the control group. In addition, 14 patients with invasive gastric cancer were included as a reference group. The association between TFF3 levels and intestinal metaplasia was assessed by logistic regression.ResultsPatients with intestinal metaplasia (n = 110) had a higher median TFF3 level as compared to controls (n = 164), 13.1 vs. 11.9 ng/mL, respectively (p = 0.024). Multivariable logistic regression showed a no significant association between TFF3 levels and intestinal metaplasia (OR = 1.20; 95%CI: 0.87–1.65; p-trend = 0.273). The gastric cancer group had a median TFF3 level of 20.5 ng/mL, and a significant association was found (OR = 3.26; 95%CI: 1.29–8.27; p-trend = 0.013).ConclusionSerum levels of TFF3 do not discriminate intestinal metaplasia in this high-risk Latin American population. Nevertheless, we confirmed an association between TFF3 levels and invasive gastric cancer.     

Low mannose-binding lectin (MBL) is associated with paediatric inflammatory bowel diseases and ileal involvement in patients with Crohn disease

BackgroundMannose-binding lectin (MBL) is a pattern-recognition molecule of the innate immune system and may be involved in the pathogenesis of inflammatory bowel disease (IBD). Our aim was to assess the prevalence of MBL deficiency in a cohort of patients with paediatric-onset IBD and study whether it is associated with the clinical manifestations, serum antibody formation, or genetic factors.MethodsThis prospective study included 159 paediatric patients (mean age: 14.0 years) with IBD [107 patients with Crohn disease (CD) and 52 patients with ulcerative colitis (UC)]. Furthermore, 95 controls were investigated. Serum samples were determined for MBL by enzyme-linked immunosorbent assay (ELISA) and for serologic markers [autoantibodies against Saccharomyces cerevisiae (ASCA) and perinuclear components of neutrophils (pANCA)] by indirect immunofluorescent assay. NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism.ResultsThe MBL serum concentration was significantly lower in IBD patients(both with CD and UC) compared to controls (IBD, p = 0.007, CD, p = 0.04, UC p = 0.004). Prevalence of low MBL level (< 500 ng/mL) was significantly higher in both CD and UC groups compared to controls (p = 0.002 and p = 0.006). Furthermore, low MBL level was associated with isolated ileal involvement (p = 0.01) and MBL deficiency (< 100 ng/mL) with male gender (p = 0.004) in patients with CD. We failed to confirm any correlation between MBL deficiency and serum autoantibodies or NOD2/CARD15 variants.ConclusionsOur results suggest that low MBL associated with paediatric-onset IBD and ileal CD may be considered an additional marker of the IBD pathogenesis.     

Neoadjuvant chemotherapy improves survival rate in advanced urothelial carcinoma

Radical surgery (RS) with adjuvant chemotherapy (AC) or radiotherapy has been conventionally used for patients with advanced urothelial carcinoma (AUC). Recent research has indicated that systemic neoadjuvant chemotherapy (NC) with RS yields better outcomes than RS alone for patients with locally advanced bladder cancer. However, there are no reports indicating whether NC or AC would be beneficial for patients with AUC. The present study compared the survival rate for AUC patients receiving NC or AC. A retrospective analysis was conducted using data for 64 patients with AUC who underwent RS and systemic chemotherapy at our institution between March 2002 and March 2011. Of the 64 patients, 30 received NC before RS and 34 received RS followed by systemic AC. Pathologic stages (p = 0.002), grades (p = 0.018) and lymphovascular invasion (p = 0.047) were significantly lower in the patients who received NC first than in those who received RC first. Furthermore, analysis of the surgical specimens revealed that 26.7% of patients who received NC before RS had complete remission. There were no significant differences in demographic data, surgical complications, and chemotoxicity between the two patient groups. The progression-free survival (PFS) and overall survival (OS) of patients who received initial NC were significantly better than those of patients who received initial RC (p = 0.002 and 0.018, respectively). Our results indicate that NC administration before RS significantly improved the PFS and OS of AUC patients, without increasing surgical complications and chemotoxicity. Further prospectively controlled trials need to be conducted to confirm the effectiveness of NC for AUC patients.     

Prospective study of matrix metalloproteinase-9 and risk of myocardial infarction and stroke in older men and women

ObjectivesThe endopeptidase matrix metalloproteinase-9 (MMP-9) is implicated in atherosclerotic plaque rupture. We investigate prospective associations between MMP-9 and MI or stroke in an older general population cohort, accounting for established and novel cardiovascular risk factors.MethodsBaseline serum MMP-9 was measured in incident MI (n = 368) and stroke (n = 299) cases and two controls per case, ‘nested’ in prospective studies of 4252 men and 4286 women aged 60–79 years, sampled from General Practices in Britain in 1998–2000, with 7-year follow-up for fatal and non-fatal MI and stroke.ResultsGeometric mean MMP-9 was 528 ng/mL (IQR 397, 743) in MI cases compared to 501 ng/mL (IQR 370, 743) in controls, p = 0.10. Participants in the top compared to bottom third of MMP-9 levels had an age-adjusted odds ratio for MI of 1.53 (95% CI 1.09, 2.13), which attenuated to 1.18 (95% CI 0.81, 1.70) after adjustment for established and novel cardiovascular risk factors. There was weak evidence that OR differed according to pre-existing CVD; the OR for MI in 187 participants with pre-existing CVD was 2.20 (1.04, 4.64) and 1.24 (0.84, 1.82) in 715 participants without (LR test for interaction p = 0.06). Geometric mean MMP-9 levels were higher in stroke cases than controls; 522 ng/mL (IQR 363, 673) vs 487 (IQR 393, 704), p = 0.045; however adjustments similarly attenuated the associations.ConclusionsWhile serum MMP-9 is univariately associated with risk of MI and stroke, it is not a strong independent risk marker for either.     

Reference interval of pregnancy-associated plasma protein-A in healthy men and non-pregnant women

ObjectiveThe serum pregnancy-associated plasma protein-A (PAPP-A) concentration is a predictor of ischemic cardiac events and renal impairment. However, the reference interval of PAPP-A has not been determined. This study determined the reference interval of PAPP-A in men and non-pregnant women.MethodsThe study enrolled 126 apparently healthy individuals (52 males and 74 females). The mean age of the men and women was 34.7 (range 20–66) years and 34.6 (range 18–65) years, respectively. Serum PAPP-A concentrations were determined using an ultrasensitive enzyme-linked immunoassay kit. Reference intervals were calculated using the bootstrap method.ResultsThe results for three subjects were outliers, so the reference interval of PAPP-A was calculated using the data for 123 subjects. PAPP-A was undetectable in 26 subjects. The reference interval of PAPP-A for men and women (with the 90% confidence interval) was <22.9 ng/mL (19.7–23.3) and <33.6 ng/mL (25.2–36.7), respectively. In male subjects, serum PAPP-A levels of smokers [3.10 (UD, 7.30) ng/mL] were significantly lower than that of non-smokers [11.00 (UD, 24.4) ng/mL] (p < 0.001) and there was a positive correlation between serum PAPP-A levels and subjects’ age (r = 0.439; p < 0.001).ConclusionsThe reference interval of PAPP-A differed for men and non-pregnant women. In clinical practice, <22.9 ng/mL for men and <33.6 ng/mL for non-pregnant women may be used as reference intervals for PAPP-A.     

Genetic and environmental factors as predictors of disease severity and extent at time of diagnosis in an inception cohort of inflammatory bowel disease,Copenhagen County and City 2003–2005

Background and aimsThe etiology of the inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) remains unknown. We aimed to investigate the influence of genetic, serological, and environmental factors on phenotypic presentation of IBD at diagnosis in a population-based Danish inception cohort from 2003–2005.MethodsThree-hundred-forty-seven (62%) of 562 cohort patients were genotyped. ASCA and p/c-ANCA were determined and patients answered a questionnaire concerning environmental factors with possible influence on IBD.ResultsFourteen percent of CD patients vs. 11% of controls were positive for common CARD15 mutation (ns), whereas more CD patients than healthy controls were homozygous for the OCTN-TC haplotype (p = 0.03). ASCA was more common in CD (22%) than UC (14%) (p = 0.045) and was related to age and localization of CD. p-ANCA was more frequent in UC (p = 0.00001) but was related to pure colonic CD (p = 0.0001). Sugar consumption was significantly higher in CD patients than in UC patients (p = 0.0001) and more CD patients than UC patients had undergone appendectomy prior to IBD diagnosis (p = 0.03). A possible relation between tonsillectomy and disease severity in CD, and a relation between use of oral contraception and disease localization of UC to rectum/left-sided colon were found.ConclusionsIn this cohort of unselected IBD patients we found a very low frequency of mutations in IBD susceptibility genes and observed a greater impact of ASCA and ANCA than of genetic factors on disease phenotypes. In addition, several environmental factors seemed to influence disease occurrence and disease presentation in both UC and especially CD.     

Evaluation of galectin-3 levels in acute coronary syndrome

Galectin-3 is a new biomarker that is assumed to reflect fibrogenesis and inflammation. In this study, we aimed to evaluate the levels of galectin-3 in patients with acute coronary syndrome (ACS) and the relation of galectin-3 to the burden of atherosclerosis. Nineteen patients with ACS who underwent coronary angiography and 17 age-matched healthy controls were enrolled. The burden of atherosclerosis was assessed with Gensini score and with the number of involved vessels. Galectin-3 levels were measured on admission by using ELISA. The mean age of the cohort was 62.8 ± 10.6 and 56% of the patients were male. Compared to control group, median galectin-3 levels were significantly higher in ACS patients (0.77 ng/mL [0.50–1.19] vs. 0.51 ng/mL [0.41–0.78], P = 0.01). Patients were classified into three groups according to the number of involved vessels. Median galectin-3 levels did not differ significantly among groups (one vessel: 0.68 ng/mL [0.55–0.74], two vessels: 0.67 ng/mL [0.46–1.84], three vessels 0.90 ng/mL [0.53–1.38], P = 0.62). There was a strong correlation between galectin-3 levels and Gensini score (r = 0.625, P = 0.004). In conclusion, galectin-3 levels were elevated in patients with ACS and there was a strong correlation between galectin-3 levels and Gensini score.     

Prevalence of Inflammatory Bowel Disease in the Canton of Vaud (Switzerland): A population-based cohort study

Background and aimsBecause of the changing epidemiology of Inflammatory Bowel Diseases (IBD), we set out to characterize the population-based prevalence of Crohn's Disease (CD) and Ulcerative Colitis (UC) in a defined population of Switzerland.MethodsAdult IBD patients were identified by a cross-matched review of histological, hospital and gastroenterologist files throughout a geographical defined population (Canton of Vaud). Demographic factors statistically significantly associated with prevalence were evaluated using a stepwise Poisson regression analysis. Results were compared to IBD prevalence rates in other population-based studies and time trends were performed, based on a systematic literature review.ResultsAge and sex-adjusted prevalence rates were 205.7 IBD (100.7 CD and 105.0 UC) cases per 10⁵ inhabitants. Among 1016 IBD patients (519 CD and 497 UC), females outnumbered males in CD (p < 0.001), but males were more represented in elderly UC patients (p = 0.008). Thus, being a male was statistically associated with UC (Relative Risk (RR) 1.25; p = 0.013), whereas being a female was associated with CD (RR 1.27; p = 0.007). Living in an urban zone was associated with both CD and UC (RR 1.49; p < 0.001, 1.63; p < 0.001, respectively). From 1960 to 2005, increases in UC and CD prevalences of 2.4% (95%CI, 2.1%–2.8%; p < 0.001) and 3.6% (95%CI, 3.1%–4.1%; p < 0.001) per annum were found in industrialised countries.ConclusionsExtrapolating our data to all of Switzerland yields an estimate of 12,000 IBD cases for the country, or 1 in 500 inhabitants. Our study gives support to an increase in IBD prevalence in Europe.     

Total soluble and endogenous secretory receptor for advanced glycation endproducts (RAGE) in IBD

Background and aimsRecruitment and activation of neutrophils, with release of specific proteins such as S100 proteins, is a feature of inflammatory bowel disease (IBD). Soluble forms of the receptor for advanced glycation endproducts (sRAGE), and variants such as endogenous secretory (esRAGE), can act as decoy receptors by binding ligands, including S100A12. The aims of this study were to determine total sRAGE and esRAGE concentrations in patients with IBD and correlate these with C-reactive protein (CRP), endoscopic scores and clinical disease activity scores.MethodsEDTA-plasma was collected from patients undergoing colonoscopy including those with Crohn's disease (CD: n = 125), ulcerative colitis (UC: n = 79) and control patients without endoscopic signs of inflammation (non-IBD: n = 156). Concentrations of sRAGE and esRAGE were determined by enzyme-linked immunosorbent assay and plasma CRP concentrations measured. Standard clinical disease activity and endoscopic severity scores were defined for all subjects.ResultsPlasma sRAGE concentrations were lower in UC (but not CD) than non-IBD subjects (p < 0.01). Whilst sRAGE concentrations correlated negatively with endoscopic activity in UC (p < 0.05), this was not seen in CD. In contrast, esRAGE correlated negatively with disease activity in both UC (p = 0.002) and CD (p = 0.0001). Furthermore, sRAGE and esRAGE concentrations correlated inversely with CRP values (p < 0.0001).ConclusionsAlthough total sRAGE varied with activity in UC, esRAGE concentrations correlated inversely with endoscopic disease activity and CRP levels in both UC and CD. Additional studies are required to further define the significance of sRAGE and esRAGE in IBD.     

Blood levels of glucose and insulin and insulin resistance in patients with schizophrenia on clozapine monotherapy

ObjectiveWe tested the hypothesis that fasting blood glucose and insulin levels are higher in schizophrenic subjects on clozapine monotherapy compared with healthy controls and they correlate with anthropometric measurements, laboratory tests and body composition.MethodsData for 24 subjects with schizophrenia treated with clozapine and 24 age- and sex-matched healthy volunteers was analyzed.ResultsPatients taking clozapine had higher fasting levels of glucose (103.5 ± 31.6 vs. 87.8 ± 11.7 mg/dL, z = −2.03, p = 0.04), there was no difference for insulin concentrations and markers of insulin resistance. In the clozapine group glucose levels correlated with clozapine dose (R = −0.43, p = 0.03), while insulin levels correlated with weight (R = 0.66, p < 0.001), body mass index (R = 0.54, p = 0.007), abdominal (R = 0.53, p = 0.007) and waist (R = 0.43, p = 0.04) circumference, total body fat (R = 0.51, p = 0.01), and uric acid levels (R = 0.50, p = 0.01). In the clozapine group insulin levels were lower in subjects with body mass index <25 kg/m² (7.0 ± 3.3 vs. 13.4 ± 8.8 μU/mL, p = 0.04) and in subjects without abdominal obesity (6.3 ± 2.4 vs. 13.3 ± 8.6 μU/mL, p = 0.03).ConclusionsWe found higher blood glucose levels in subjects taking clozapine and no differences in blood insulin levels between subjects with schizophrenia and controls. Associations between blood insulin levels and abdominal/waist circumferences support the role of abdominal obesity as an important risk factor of insulin resistance.