Serum ficolin-2 correlates worse than fecal calprotectin and CRP with endoscopic Crohn's disease activity

Background and aimsFicolin-2 is an acute phase reactant produced by the liver and targeted to recognize N-acetyl-glucosamine which is present in bacterial and fungal cell walls. We recently showed that ficolin-2 serum levels were significantly higher in CD patients compared to healthy controls. We aimed to evaluate serum ficolin-2 concentrations in CD patients regarding their correlation with endoscopic severity and to compare them with clinical activity, fecal calprotectin, and CRP.MethodsPatients provided fecal and blood samples before undergoing ileo-colonoscopy. Disease activity was scored clinically according to the Harvey–Bradshaw Index (HBI) and endoscopically according to the simplified endoscopic score for CD (SES-CD). Ficolin-2 serum levels and fecal calprotectin levels were measured by ELISA.ResultsA total of 136 CD patients were prospectively included (mean age at inclusion 41.5 ± 15.4 years, 37.5% females). Median HBI was 3 [2–6] points, median SES-CD was 5 [2–8], median fecal calprotectin was 301 [120–703] μg/g, and median serum ficolin-2 was 2.69 [2.02–3.83] μg/mL. SES-CD correlated significantly with calprotectin (R = 0.676, P < 0.001), CRP (R = 0.458, P < 0.001), HBI (R = 0.385, P < 0.001), and serum ficolin-2 levels (R = 0.171, P = 0.047). Ficolin-2 levels were higher in CD patients with mild endoscopic disease compared to patients in endoscopic remission (P = 0.015) but no difference was found between patients with mild, moderate, and severe endoscopic disease.ConclusionsFicolin-2 serum levels correlate worse with endoscopic CD activity when compared to fecal calprotectin or CRP.     

Hand-held fractional exhaled nitric oxide measurements as a non-invasive indicator of systemic inflammation in Crohn's disease

Background and aimsActive inflammatory bowel disease (IBD) is associated with increased activity of inducible nitric oxide synthase (iNOS), which increases both mucosal and plasma nitric oxide (NO) levels. Increased fractional exhaled nitric oxide (FeNO) levels have been described in patients with IBD. Currently, hand-held FeNO measurement devices are available, enabling a fast in-office analysis of this non-invasive disease activity marker. In this pilot study, we investigated the utility of in-office FENO measurements in patients with Crohn's disease (CD).MethodsFifty CD patients and 25 healthy controls (HC) were included, all of whom were free of atopic or pulmonary disorders and respiratory symptoms at the time of inclusion. The Crohn's disease activity index (CDAI) was calculated, and the inflammatory parameters and fecal calprotectin levels were assessed. FeNO was measured with a hand-held device.ResultsA significant increase in FeNO (median, [interquartile range]) was observed in steroid-free CD patients with clinically active disease (CDAI > 150; 22 [8] ppb) compared with CD patients in clinical remission (CDAI < 150; 11 [6] ppb; P < 0.001) and HC's (17 [9] ppb; P < 0.05). Active CD patients treated with corticosteroids had significantly lower FeNO compared with active CD patients without steroids (12 [10] ppb vs 25 [19] ppb; P < 0.05). FeNO displayed a strong correlation with the CDAI (R = 0.68; P < 0.001). Fair correlations were found between FeNO and several systemic inflammatory markers, but no significant correlation was found with fecal calprotectin.ConclusionThis pilot study suggests that hand-held FeNO measurements could be an attractive non-invasive indicator of systemic inflammation in Crohn's disease.     

A new rapid test for fecal calprotectin predicts endoscopic remission and postoperative recurrence in Crohn's disease

IntroductionFecal calprotectin (FC), as determined by the enzyme-linked immunoassay (ELISA) test, has been proposed as a promising biomarker of endoscopic activity in Crohn's disease (CD). However data on its accuracy in predicting endoscopic remission according to location and postoperative recurrence (POR) is scarce.Our objective was to evaluate the ability of FC determined by a new quantitative point-of-care test (FC-QPOCT) to predict endoscopic remission and POR in CD patients.MethodsFC was determined simultaneously by an enzyme-linked immunoassay test (FC-ELISA) and a FC-QPOCT in CD patients undergoing colonoscopy. Clinical disease activity was assessed according to the Crohn's Disease Activity Index (CDAI). Endoscopic results were assessed according to the Crohn's Disease Endoscopic Activity Index of Severity (CDEIS) and postoperative recurrence according to the Rutgeerts' score.ResultsA total of 115 ileocolonoscopies were performed (29 on patients with ileocolonic resection). FC levels correlated more closely with the CDEIS than leucocytes, platelets or CRP. The prediction of “endoscopic remission” (CDEIS < 3), using FC-QPOCT (cut-off 272 μg/g) and FC-ELISA (cut-off 274 μg/g) presented an AUC of 0.933 and 0.935 respectively. FC-QPOCT results correlated better with endoscopic activity in the ileocolonic location (Pearson's correlation, r = 0.879; P < 0.001), than the colonic (r = 0.725; P < 0.001) or the ileal location (r = 0.437; P = 0.016). Median FC-QPOCT levels discriminated Rutgeerts' score i0–i1 from i2–i4 (98 (range 30–306) μg/g vs. 234.5 (range 100–612) μg/g respectively, P = 0.012).ConclusionsFC determined by rapid quantitative test predicts “endoscopic remission” and endoscopic postoperative recurrence in CD patients.     

Trough s-infliximab and antibodies towards infliximab in a cohort of 79 IBD patients with maintenance infliximab treatment

Background and AimsThe anti-TNF antibody infliximab is effective in inducing remission in Crohn's disease as well as in ulcerative colitis and many patients are treated for several years with sustained clinical remission. However, the role of monitoring s-infliximab and antibodies towards infliximab during maintenance treatment remains unclear. Our aim was to correlate serum drug levels and antibodies to clinical activity, CRP, albumin and concomitant immunosuppression in a cohort on maintenance infliximab treatment.MethodsWe included 79 patients with Crohn's disease or ulcerative colitis who had responded to infliximab and received maintenance treatment (4–69 infusions) in this retrospective study. Infliximab levels and antibodies towards the drug were analyzed with in-house-developed ELISA assays.ResultsThe mean s-infliximab was significantly higher in patients in remission (4.1 μg/mL) as compared with disease flare (mean 1.8 μg/mL); p < 0.001. The s-infliximab showed a significant negative correlation with Harvey–Bradshaw index (r = − 0.21; p < 0.05). Serum-infliximab progressively decreased with the number of accumulated infusions (p < 0.05). In patients with undetectable trough levels, 55% of the patients with concomitant immunosuppressive were positive for antibodies against infliximab, as compared with 94% of patients on monotherapy. Patients with undetectable serum-infliximab were in clinical remission at 25% of the visits.ConclusionsThe trough level 4.1 μg/mL may serve as cut-off for clinical remission. Drug trough levels decreased during treatment and almost all patients with undetectable s-infliximab and monotherapy had developed antibodies against the drug.     

Infliximab trough levels and persistent vs transient antibodies measured early after induction predict long-term clinical remission in patients with inflammatory bowel disease

BackgroundThe use of therapeutic drug monitoring has been proposed as a useful tool in the management of patients with loss of response to biological therapy in patients with inflammatory bowel disease.AimsTo evaluate whether early, post-induction anti-tumor necrosis factor trough levels and the presence of different types of anti-drug antibodies may impact long-term clinical remission in patients with inflammatory bowel disease.MethodsWe prospectively assessed anti-tumor necrosis factor trough levels and both persistent and transient anti-drug antibodies. The Harvey–Bradshaw Index and the partial Mayo score were evaluated at each visit or in case of relapse.ResultsAt week 14, median infliximab trough levels were significantly lower in patients who experienced loss of response at week 48 as compared to patients in stable remission (1.3 mcg/mL [range 0–10.2 mcg/mL] vs. 10.1 mcg/mL[range 0–42.8 mcg/mL], P < 0.0004). ROC curve identified an infliximab trough levels of 6.2 mcg/mL as the cut-off value with the highest accuracy (c-index = 0.864) for loss of response at week 48. At week 14 we observed a correlation between anti-drug antibodies concentration and infliximab trough levels (r_s = −0.513, P = 0.04).ConclusionsThe results highlight the usefulness of assessing early biological TL in order to predict patients’ long-term outcome.     

Fast and sharp decrease in calprotectin predicts remission by infliximab in anti-TNF naïve patients with ulcerative colitis

AimTo evaluate the effect of infliximab induction therapy on calprotectin levels in patients with ulcerative colitis (UC).Patients and MethodsIn this prospective study 53 patients with active UC from 17 centers were treated with infliximab therapy (5 mg/kg) at baseline, week 2, and week 6. Faecal calprotectin was measured every week. Sigmoidoscopies were performed at baseline, week 6 and week 10.ResultsMedian calprotectin levels decreased from 1260 (IQR 278.5- 3418 ) at baseline to 72.5 (IQR 18.5 - 463) at week 10 (p < 0.001). After 10 weeks, infliximab therapy induced endoscopic remission and a decrease in calprotectin to < 50 mg/kg or at least a 80% decrease from baseline level in 58% of patients.A significant and steep decrease of calprotectin levels was seen at week 2 for patients with an endoscopic remission at week 10 as compared to patients who did not show a remission. (p < 0.001).At week 10 an excellent correlation was found between endoscopic remission and clinical Mayo score reflected by an AUC of ROC analyses of 0.94 (0.87-1) and with calprotectin measurements (AUC 0.91 (0.81-1)) : all patients with calprotectin levels < 50 mg/kg, and a normal clinical Mayo score (= 0) were in endoscopic remission.ConclusionsInfliximab induces a fast and significant decrease of faecal calprotectin levels in anti-TNF naïve patients with ulcerative colitis predictive for remission of disease     

Fecal calprotectin one year after ileocaecal resection for Crohn's disease — A comparison with findings at ileocolonoscopy

Background and AimsIleocaecal resection for Crohn's disease is commonly performed. The severity of endoscopic lesions in the anastomotic area one year postoperatively is considered to reflect the subsequent clinical course.Fecal calprotectin (FC) has been shown to correlate with the findings at ileocolonoscopy in Crohn's disease. The objectives of this study were to assess whether the concentration of FC reflects the endoscopic findings one year after ileocaecal resection and to evaluate the variation of FC in individual patients during 6 months prior to the ileocolonoscopy.MethodsThirty patients with Crohn's disease and ileocaecal resection performed within one year were included. Stool samples were delivered monthly until an ileocolonoscopy was performed one year postoperatively.ResultsOne year after surgery the median values of FC were not significantly different between the patients in endoscopic remission (n = 17) and the patients with an endoscopic recurrence (189 (75–364) vs 227 (120–1066)μg/g; p = 0.25). However, most patients with low values were in remission and all patients with high (> 600 μg/g) calprotectin values had recurrent disease. The variability of the FC concentration was most pronounced in patients with diarrhea.ConclusionsWe found no statistical difference in the concentrations of calprotectin between patients in endoscopic remission and patients with a recurrent disease one year after ileocaecal resection for Crohn's disease. However, among the minority of patients with low or high values, FC indicated remission and recurrence, respectively. There was significant variation of the fecal calprotectin concentrations over time, which affects the utility of calprotectin in clinical practice.     

Anti-TNF-α antibodies improve intestinal barrier function in Crohn's disease

Background and aimsIntestinal barrier function in Crohn's disease patients and their first degree healthy relatives is impaired. The increased intestinal permeability may result in an enhanced mucosal immune response and thereby aggravate intestinal inflammation. Humanised anti-TNF-α antibodies have been shown to be effective in the treatment of active Crohn's disease and in the treatment of entero-cutaneous fistula.The aim of the present study was to investigate the influence of anti-TNF-α antibody (infliximab) treatment on the intestinal barrier function of patients with active Crohn's disease.MethodsThe differential intestinal uptake of lactulose and mannitol was measured to quantify intestinal permeability in patients with long standing active Crohn's disease (n = 17) directly before and seven days after treatment with infliximab (5 mg/kg bodyweight). In parallel, intestinal permeability was studied in a healthy control group (n = 20). Serum samples were analysed with pulsed amperometric detection after separation on an anion exchange column.ResultsIntestinal permeability was significantly increased in all patients with Crohn's disease (L/M ratio 0.24 ± 0.17) prior to infliximab treatment compared to the control group (L/M ratio 0.01 ± 0.02; p-value < 1 × 10^− 7). Treatment of patients with infliximab resulted in a marked decrease of intestinal permeability as measured by L/M ratio from 0.24 ± 0.17 before to 0.02 ± 0.02 (p-value < 1 × 10^− 7) seven days after infliximab application.ConclusionsTreatment with anti-TNF-α antibodies improved impaired intestinal barrier function in patients with Crohn's disease. This effect may correlate to the well documented anti-inflammatory effect of TNF-α blockade in this intestinal disease.     

Usefulness of abdominal ultrasonography in the analysis of endoscopic activity in patients with Crohn's disease: Changes following treatment with immunomodulators and/or anti-TNF antibodies

ObjectiveThe objective of this study was to analyze the accuracy of abdominal ultrasonography (AUS) in the assessment of mucosal healing in patients with Crohn's disease (CD) receiving immunomodulators and/or biological treatment, with ileocolonoscopy as the reference standard.Materials and MethodsThirty patients were included in a prospective longitudinal study. All patients underwent ileocolonoscopy and AUS before and after a minimum of one year of treatment. The Crohn's Disease Endoscopic Inflammatory Index of Severity (CDEIS) was used for endoscopic assessment whereas AUS was analyzed by means of bowel wall thickness, color Doppler grade and percentage of increase of parietal enhancement after contrast injection.ResultsIn the segmental analysis, endoscopic healing was found in 71.2% of the segments and AUS findings were normalized in 62.8%, with a significant correlation between the two techniques (κ = 0.76, p < 0.001). In the overall assessment performed after treatment, 18 (60%) patients exhibited endoscopic remission (CDEIS < 6 points); of these patients, 15 (83.3%) had normalized sonographic findings, with a good correlation between endoscopic remission and sonographic normalization (κ = 0.73, p < 0.001). Of the three variables assessed by AUS, parietal thickness was the best variable to predict mucosal healing in both analyses, segmental and global.ConclusionAbdominal ultrasonography is a useful and reliable technique for the assessment of the endoscopic response to treatment with immunomodulators and/or biological drugs in Crohn's disease. AUS is a highly accurate technique for evaluating the healing of the intestinal mucosa.     

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.     

Disfunción endotelial en niños con enfermedad renal crónica

Background and objectiveCardiovascular disease is the main cause of death in children with chronic kidney disease. Inflammation and endothelial dysfunction are found in the majority of these patients and are factors associated to cardiovascular disease. Flow mediated dilatation (FMD) is a surrogate marker validated for evaluating endothelial dysfunction. Our objective was to identify risk factors associated to endothelial dysfunction in children with chronic kidney disease.Materials and methodsChildren 2-16 years of age were studied. Clinical information and biochemical variables were gathered, including intact parathyroid hormone (iPTH), interleukins 6 and 1β, high sensitivity C reactive protein (hsCRP), reduced glutathione, nitric oxide, malondialdehyde and homocysteine. FMD was measured, and considered altered if < 7%.ResultsIncluded were 129 patients aged 13.1 ± 2.6 years. FMD < 7% was found in 69 (52.7%). Patients with altered FMD had higher levels of triglycerides and hsCRP than those with normal FMD (145.5 vs. 120.0 mg/dL, P = .042, and 1.24 vs. 0.55 U/L, P = .007, respectively), as well as higher frequency of low iPTH (19.1 vs. 4.9%, P = .036). Levels of hsCRP correlated significantly with FMD (Rho = −0.28, P = .003). Patients with low iPTH (OR 4.41, 95% CI 1.13-17.27, P = .033) and increased hsCRP (OR 2.89, 95% CI 1.16-7.17, P = .022) had higher adjusted risk of having FMD < 7%.ConclusionsHypertriglyceridemia, inflammation and low iPTH associated significantly with altered FMD. They are frequent, treatable risk factors for cardiovascular disease.     

Serum levels of Apelin-36 are decreased in older hospitalized patients with heart failure

PurposeApelin is an endogenous peptide, it is a potent inotropes, a peripheral vasodilator, involved in fluid homeostasis, balancing the harmful effects of Ang-II-AT1 system. The apelin-APJ axis is down regulated in chronic heart failure (CHF), but the role of apelin has not yet been studied in elderly patients with CHF. The aim of our study is to investigate serum levels of apelin-36 in a group of older subjects with CHF.Subjects/Materials and methodsThe study population consisted of 30 consecutive patients aged 80 ± 7.8 years with CHF. Serum apelin levels were quantified by enzyme immunoassay (ELISA). Results were considered significant if P was < 0.05.ResultsMean values of apelin-36 in CHF patients were 0.47 ± 0.21 ng/mL, and 0.95 ± 0.37 ng/mL in control subjects (P < 0.0001). Patients in IV NYHA class showed lower levels of apelin (0.38 ± 0.16 ng/mL). Direct correlations between apelin levels and ADLs (P = 0.0008, r = 0.61), and IADLs (P = 0.008, r = 0.50) were observed.Discussion and conclusionsThis study confirms that apelin levels are decreased in patients with CHF, also in the elderly and frail; since apelin represents a potential, promising novel therapeutic target for patients with CHF, geriatric patients should be considered for future clinical trials.     

Correlation of metabolic syndrome severity with cardiovascular health markers in adolescents

Background and ObjectivesThe presence of metabolic syndrome (MetS) in childhood is a significant risk factor for later cardiovascular disease (CVD). Recent data showed temporal decreases in a sex- and race/ethnicity-specific MetS severity z-score among U.S. adolescents. Our goal was to characterize the relationship of this MetS z-score with other CVD risk indicators and assess their temporal trends and lifestyle influences.MethodsWe analyzed 4837 participants aged 12–20 years from the National Health and Nutrition Examination Survey by 2-year waves from 1999 to 2012. We used linear regression to compare MetS z-score and dietary factors with serum levels of low-density lipoprotein (LDL), apolipoprotein-B (ApoB), high-sensitivity C-reactive protein (hsCRP) and uric acid.ResultsMetS severity z-score was positively correlated with LDL, ApoB, hsCRP, and uric acid measurements (p < 0.0001 for all). These correlations held true among individual racial/ethnic groups. LDL, ApoB, and hsCRP measurements decreased over time among U.S. adolescents (p = 0.002, p < 0.0001, and p = 0.024, respectively). Saturated fat consumption was positively correlated with LDL (p = 0.005) and ApoB (p = 0.012) and inversely related to serum uric acid (p = 0.001). Total caloric intake was inversely related to LDL (p = 0.003) and serum uric acid (p = 0.003). Unsaturated fat, carbohydrate, and protein consumption were not related to LDL, ApoB, hsCRP, or serum uric acid.ConclusionsThere is a positive correlation between MetS severity and all four CVD risk indicators studied. LDL, ApoB, and hsCRP showed favorable temporal trends, which could be related to similar trends in MetS z-score. These data support the importance of considering multiple inter-related factors in clinical CVD risk assessment.     

Does fecal calprotectin predict relapse in patients with Crohn's disease and ulcerative colitis?

Background and aimsAn evaluation is made of the utility of fecal calprotectin in predicting relapse in patients with inflammatory bowel disease (IBD). The possible differences in its predictive capacity in Crohn's disease (CD) versus ulcerative colitis (UC), and the different phenotypes, are also examined.MethodsThis is a prospective study with 135 patients diagnosed with IBD in clinical remission for at least 3 months. The patients submitted a stool sample within 24 hours after the baseline visit, for the measurement of fecal calprotectin. All patients were followed-up on for one year.ResultsSixty-six patients had CD and 69 UC. Thirty-nine (30%) suffered from relapse. The fecal calprotectin concentration was higher among the patients with relapse than in those that remained in remission: 444 µg/g (95% CI 34–983) versus 112 µg/g (95% CI 22–996); p < 0.01. Patients with CD and calprotectin > 200 µg/g relapsed 4 times more often than those with lower marker concentrations. In UC, calprotectin > 120 µg/g was associated with a 6-fold increase in the probability of disease activity outbreak. The predictive value was similar in UC and CD with colon involvement and inflammatory pattern. In this group, calprotectin > 120 µg/g predicted relapse risk with a sensitivity of 80% and a specificity of 60%. Relapse predictive capacity was lower in patients with ileal disease.ConclusionsFecal calprotectin may be a useful marker for predicting relapse in patients with IBD. Its predictive value is greater in UC and CD with colon involvement and inflammatory pattern, compared with ileal CD.     

Correlación entre la endoscopia y la ecografía intestinal para la evaluación de la recurrencia posquirúrgica de la enfermedad de Crohn

ObjectiveIntestinal ultrasound is considered to be a valid alternative for the evaluation of post-operative recurrence (POR) of Crohn's disease. The aim of this study is to assess the correlation between ultrasound and endoscopic findings.MethodsPatients with Crohn's disease were retrospectively recruited who had undergone ileocecal resection, and for whom a colonoscopy and intestinal ultrasound had been performed for the detection of POR. Recurrence was assessed using the Rutgeerts score (RS). The ultrasound findings analysed were bowel wall thickness (BWT), parietal hyperaemia using power Doppler, loss of layer pattern and mesenteric fat hypertrophy.ResultsA total of 31 patients were included, of which 15 (48.4%) had no POR (RS < 2b) and 16 (51.6%) had POR (RS ≥ 2b). A statistically significant association was identified between BWT and the presence of endoscopic recurrence (a mean of 2.75 mm vs. 5.68 mm, P>0.001). There was also a statistically significant difference in hyperaemia between the 2 groups (P=0.03). For wall thickness, an area under the ROC curve (AUC) of 92.9% was obtained, and with a cut-off point of 3.4 mm, a sensitivity of 100% and specificity of 86.6%. When comparing with the most frequent biomarkers (fecal calprotectin and serum CRP), a higher AUC was obtained for wall thickness (72.3% and 72.3% vs. 92.9%).ConclusionsIn our experience, ultrasound has high diagnostic efficacy in the detection of POR and can be considered a valid non-invasive alternative to endoscopy.     

The risks of post-operative complications following pre-operative infliximab therapy for Crohn's disease in patients undergoing abdominal surgery: A systematic review and meta-analysis

BackgroundInfliximab is an anti-TNF alpha blocker frequently utilized in the management of moderate to severe Crohn's Disease. The immunosuppressive effects of infliximab may increase the risk for post-operative complications among Crohn's Disease patients undergoing abdominal surgery. We conducted a systematic review and meta-analysis of studies comparing the rates of post-operative complications among Crohn's disease patients treated with Infliximab therapy versus alternative therapies.MethodsWe used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and searched 4 electronic databases along with major conference abstract databases from inception of database until November, 2012. English-language articles and abstracts evaluating post-operative complications among Crohn's disease patients were considered eligible. We applied meta-analysis with random effects model to calculate the overall odds ratio for total major complications as well as several secondary outcomes.ResultsData were extracted from six studies including 1159 patients among whom 413 complications were identified. The most common complications were wound infections, anastomotic leak and sepsis. There was no significant difference in the major complication rate (OR = 1.59[95% C.I.: 0.89–2.86]; p = 0.15), minor complication rate (OR = 1.80 [C.I.: 0.87–3.71]; p = 0.11), reoperation rate (OR = 1.33 [C.I.: 0.55–3.20]; p = 0.52) or 30 day mortality rate (OR = 3.74 [C.I.: 0.56–25.16]; p = 0.13) between the Infliximab and control groups.ConclusionsThis meta analysis provides some evidence that infliximab may be safe to continue in the pre-operative period without increasing the risk of post-operative complications for Crohn's disease patients undergoing abdominal surgery.     

Crohn's disease outcome in patients under azathioprine: A tertiary referral center experience

Background and aimsAzathioprine is of major importance in the treatment of Crohn's disease; its efficacy has been showed in several works, but real-life data regarding its use is scarce. Our aim was to address the outcome of patients with Crohn's disease under azathioprine in the real-life setting.MethodsCrohn's disease patients followed at an Inflammatory Bowel Disease Outpatient Clinic under azathioprine were consecutively enrolled, being allocated in one of four groups. Two groups included patients on treatment with this drug, regarding its two major indications — prevention of post-operative recurrence and steroid-dependent disease; a third group included patients who needed infliximab in addition to azathioprine and a fourth group comprised patients who did not tolerate azathioprine.ResultsA total of 221 patients were enrolled, 180 on azathioprine due to steroid-dependency (64 needing additional treatment with infliximab) and 41 for prevention of post-operative recurrence. Steroid-free remission was obtained in 48%. Immunosuppression decreased the number of hospitalized patients (64% vs 36%; p < 0.001), but not the surgery rates per person per year. Azathioprine as a post-operative drug was effective in decreasing hospitalizations. The addition of infliximab decreased the number of patients hospitalized (p = 0.009) and hospitalization rates per person per year (p < 0.001), but had no effect in the surgery rates per person per year. Sixty patients (23%) experienced adverse effects with AZA, 39 requiring discontinuation of the drug.ConclusionsIn this real-life study, azathioprine had a long-term steroid sparing effect and reduced hospitalizations. Combination with infliximab reduced hospitalizations but did not decrease the surgery rate.     

The Relationship Between Neutrophil Lymphocyte Ratio With Urinary Protein Albumin Excretion in Newly Diagnosed Patients With Type 2 Diabetes

BackgroundRecent evidence suggests that neutrophil/ lymphocyte (N/L) ratio play a role in the development and progression of cardiovascular complications. Increased urinary albumin and protein excretion has been shown to be a risk factor for cardiovascular disease. Thus, this study aimed to investigate the relationship between circulating total and differential leukocyte counts including N/L ratio with urinary protein and albumin excretion in patients with newly diagnosed type 2 diabetes.MethodsAll patients underwent history taking, physical examination, blood pressure measurement, 12-lead electrocardiographic evaluation, routine urine analysis, biochemical analysis, 24-hour urine collection to measure protein and albumin excretion and creatinine clearance. Peripheral total and differential leukocyte analyses were performed using an automated cell counter.ResultsIn total, 80 patients were included. spearman correlation analysis revealed that 24-hour urinary protein excretion was correlated with neutrophil count (ρ = 0.280, P = 0.012), lymphocyte count (ρ = − 0.365, P = 0.001) and N/L ratio (ρ = 0.474, P < 0.0001). Spearman correlation analysis revealed that 24-hour urinary albumin excretion was correlated with neutrophil count (ρ = 0.261, P = 0.019), lymphocyte count (ρ = − 0.278, P = 0.013) and N/L ratio (ρ = 0.415, P < 0.0001). In stepwise linear regression analysis, 24-hour urinary protein excretion was independently associated with high-density lipoprotein cholesterol (P = 0.01), blood urea (P = 0.014) and N/L ratio (P = 0.041). On the other hand, 24-hour urinary albumin excretion was independently associated with creatinine clearance (P = 0.004), albumin (P < 0.0001) and N/L ratio (P = 0.011).ConclusionsThis study demonstrated that increased N/L ratio was independently related with both 24-hour urinary protein and urinary albumin excretion in newly diagnosed patients with type 2 diabetes.     

Performance of Simplified Modification of Diet in Renal Disease and Cockcroft-Gault Equations in Patients With Chronic Spinal Cord Injury and Chronic Kidney Disease

IntroductionThe purpose of the study was to compare the performance of the simplified Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (CG) equations with 24-hour urinary creatinine clearance (Ccr) in patients with spinal cord injury (SCI) and chronic kidney disease.MethodsA retrospective diagnostic accuracy study of 116 patients with chronic SCI followed at the Memphis Veterans Affairs Medical Center Spinal Cord Injury Unit with measured Ccr (mCcr) < 90 mL/min/1.73 m².ResultsLinear regression analysis relating estimated glomerular filtration rate (eGFR) to mCcr showed a highly significant correlation between mCcr and eGFR (n = 116; r = 0.81, r² = 0.65, P < 0.0001); however, the relationship was more variable in the quadriplegic subjects (n = 52; r = 0.74, r² = 0.54, P < 0.0001) than in the paraplegic subjects (n = 64; r = 0.86, r² = 0.73, P < 0.0001). Both eGFR equations overestimated glomerular filtration rate (GFR) at all ranges of GFR in both subgroups of paraplegic subjects and quadriplegic subjects, with an MDRD fractional prediction error of 49% and 62%, respectively. Addition of a correction factor of 0.7 for MDRD and 0.8 for CG equations resulted in clinically acceptable fractional prediction error (below 20%) in both subgroups, especially in paraplegics with 3.9% and 3.6%, respectively. There was marked improvement in the performances of both eGFR equations, with better accuracy and precision after application of the correction factors.ConclusionsBoth MDRD and CG equations overestimate GFR in patients with chronic SCI at all stages of chronic kidney disease, particularly in quadriplegic subjects. An empirically derived correction factor markedly improved the performance and accuracy of both prediction equations.     

When do we dare to stop biological or immunomodulatory therapy for Crohn's disease? Results of a multidisciplinary European expert panel

BackgroundSafety and economic issues have increasingly raised concerns about the long term use of immunomodulators or biologics as maintenance therapies for Crohn's disease (CD). Despite emerging evidence suggesting that stopping therapy might be an option for low risk patients, criteria identifying target groups for this strategy are missing, and there is a lack of recommendations regarding this question.MethodsMultidisciplinary European expert panel (EPACT-II Update) rated the appropriateness of stopping therapy in CD patients in remission. We used the RAND/UCLA Appropriateness Method, and included the following variables: presence of clinical and/or endoscopic remission, CRP level, fecal calprotectin level, prior surgery for CD, and duration of remission (1, 2 or 4 years).ResultsBefore considering withdrawing therapy, the prerequisites of a C-reactive protein (CRP) and fecal calprotectin measurement were rated as “appropriate” by the panellists, whereas a radiological evaluation was considered as being of “uncertain” appropriateness. Ileo-colonoscopy was considered appropriate 1 year after surgery or after 4 years in the absence of prior surgery. Stopping azathioprine, 6-mercaptopurine or methotrexate mono-therapy was judged appropriate after 4 years of clinical remission. Withdrawing anti-TNF mono-therapy was judged appropriate after 2 years in case of clinical and endoscopic remission, and after 4 years of clinical remission. In case of combined therapy, anti-TNF withdrawal, while continuing the immunomodulator, was considered appropriate after two years of clinical remission.ConclusionA multidisciplinary European expert panel proposed for the first time treatment stopping rules for patients in clinical and/or endoscopic remission, with normal CRP and fecal calprotectin levels.