Significant change in ZAP‐70 expression during the course of chronic lymphocytic leukemia

Introduction: It is widely accepted that expression of ZAP‐70 in chronic lymphocytic leukemia (CLL) remains stable in time. However, data supporting this notion are surprisingly scarce. Therefore, we assessed expression of ZAP‐70 in serial samples taken during the course of the disease. Patients and Methods: We studied 44 patients with CLL diagnosed according to NCI‐WG criteria (34 men, 10 women, median age 62, range, 36–81). A total of 104 samples were examined; all patients had at least two measurements. Median interval between the first and the second sample was 13 months (range, 2–36). ZAP‐70 expression was detected by flow cytometry using phycoerythrin‐conjugated monoclonal antibody clone 1E7.2 and negative isotype control. Twenty percent of positive cells were considered as the threshold of positivity. Results: Significant change in ZAP‐70 expression (i.e. from positivity to negativity and vice versa) was detected in 15/44 patients (34%). Interestingly, 7/8 patients whose ZAP‐70 expression converted to positivity had unmutated IgVH genes. In addition, the conversion was accompanied by clinical progression or relapse in all but one patient. On the other hand, 5/7 patients with loss of ZAP‐70 had stable clinical course. One patient became ZAP‐70‐negative during treatment with prednisone for autoimmune hemolytic anemia. Conclusions: In contrast to commonly accepted opinion, significant change in ZAP‐70 expression in time was detected in a substantial proportion of our patients with CLL. While the conversion to ZAP‐70 negativity was found predominantly in patients with stable disease, change to positivity was typical in patients with unmutated IgVH genes at the time of progression or relapse. Based on our pilot results, repeated assessment of ZAP‐70 expression might be especially useful at the time of progression or relapse in patients who were initially ZAP‐70‐negative.     

Clinical utility of molecular and flow cytometric markers in chronic lymphocytic leukaemia

Background: Chronic lymphocytic leukaemia (CLL) is a clinically heterogeneous disease. While immunoglobulin variable region heavy chain (IgVH) mutational status remains the ‘gold standard’ in molecular prognostication, a range of additional markers is increasingly being used in clinical trials. As awareness of trial data increases, requests to determine these prognostic markers for new CLL patients are becoming more prevalent in Australia. Aim: To explore the clinical utility of currently available prognostic markers for CLL in an Australian cohort. Methods: IgVH mutational status and gene usage was determined and compared with other reported immunophenotypic markers, cytogenetics and clinical outcome as defined by treatment‐free survival (TFS), lymphocyte doubling time and clinical stage in a cohort of 65 CLL patients. Results: An unmutated IgVH gene, high expression of CD38, ZAP‐70, CD25, CD49d, CD54 or low expression of CD49c was associated with shorter TFS indicating an adverse clinical prognosis in our cohort. High expression of each of CD38, ZAP‐70, CD49d and CD54 was significantly associated with an unmutated IgVH gene; however, associations were not absolute. IgVH and CD25 expression retained their significance in multivariate analysis. Concordant CD25^high/IgVH unmutated CLL patients had the shortest median TFS interval (40 months) in our cohort. Conclusions: Molecular and immunophenotypic markers remain useful as adjuncts to clinical prognostication; however, as single parameters they are unable to dictate the timing of therapeutic intervention. The combined use of CD25 and IgVH mutational status may be clinically relevant to CLL prognostication while also providing insight into the biological pathways involved in disease progression.     

Serum adenosine deaminase activity as a predictor of disease severity in ulcerative colitis

Background and aimUlcerative colitis (UC) is a chronic inflammatory disease characterized by recurrent inflammation and ulcerations of colonic mucosa and an inappropriate and delayed healing. Adenosine deaminase (ADA) is a cytoplasmic enzyme involved in the catabolism of purine bases, capable of catalyzing the deamination of adenosine, forming inosine in the result process. Although ADA has been shown to increase in several inflammatory conditions, there are no literature data indicating an alteration in UC.MethodsThis study evaluated the activity of total ADA in serum of 43 patients with UC and 18 healthy controls. Patients’ age, disease duration, drug intake, and other medical history were all noted for each subject. Complete blood count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were determined for both patients and controls. Correlation analysis was also performed between ADA and other inflammation markers of UC.ResultsSerum mean ADA levels were 11.12 ± 2.03 and 7.99 ± 2.04 U/l for patients with UC in active state and in remission and 8.55 ± 2.26 U/l in the healthy control group. Mean serum ADA levels were significantly elevated in active UC patients compared with patients with UC in remission and control groups. Overall accuracy of ADA in determination of active UC was 83.7 with sensitivity 83.3%, specificity 84.2%.ConclusionsSerum ADA levels were found to be elevated in UC patients in active state suggesting a partial role of activated T-cell response in the disease pathophysiology. Further randomized controlled studies are warranted to demonstrate the role of ADA in UC patients, with a special interest in specifically targeted therapies against ADA for achieving disease remission.     

Microinflammation in patients with Crohn's disease in clinical remission

Background and aimsIt is not clear whether Crohn's disease patients in clinical remission (Crohn's disease activity index < 150) display normal concentrations of inflammation sensitive biomarkers. Our goal in this work was to explore the intensity of the microinflammatory response in a group of Crohn's disease patients in clinical remission.MethodsHigh sensitivity C-reactive protein, quantitative fibrinogen, erythrocyte sedimentation rate as well as platelet and leukocyte counts were examined in a group of 76 patients with Crohn's disease in remission and in 228 matched controls.ResultsCrohn's disease patients in clinical remission displayed a statistically significant (p < 0.001) elevated concentration of hs-CRP (4.83 ± 3.8 mg/l) compared to controls (1.05 ± 2.9 mg/l). All other bio-markers were also significantly higher in Crohn's disease patients in remission compared to controls. Similar results were obtained in a subgroup of Crohn's disease patients with very low disease activity — CDAI < 75.ConclusionsClinical remission is not equivalent to biochemical remission raising a question concerning the true definition of remission in Crohn's disease.     

Neuroimmune interactions in patients with inflammatory bowel diseases: Disease activity and clinical behavior based on Substance P serum levels

Background and aimThe neuropeptide Substance P, plays a key role in modulating neuroimmune interactions in patients with inflammatory bowel diseases. We analyzed Substance P serum levels in patients with ulcerative colitis and Crohn's disease, to detail the involvement of the neuropeptide in the pathophysiology of these disorders.MethodsSerum samples were collected from 61 patients with ulcerative colitis (24 with active and 37 with inactive disease), 66 patients with Crohn's disease (29 with active and 37 with inactive disease) and 45 healthy subjects, enrolled into the study. Neuropetide serum levels were measured by means of an ELISA/EIA. Associations with disease activity and patients clinical features were also taken into account.ResultsCompared to controls, Substance P serum levels were significantly increased in both patients with ulcerative colitis and Crohn's disease, (p < 0.001). In patients with ulcerative colitis, levels paralleled disease activity (p = 0.014), and the amount of the neuropeptide was considerably decreased during clinical and endoscopic remission of the disease, (p = 0.025). Conversely, median Substance P levels did not differ between patients with active and inactive Crohn's disease. However, levels of the neuropeptide were more often elevated in patients with inactive and stricturing/fistulizing Crohn's disease, (p = 0.002).ConclusionsData underline that Substance P might exerts important immunomodulatory functions in inflammatory bowel disease. This study suggests a potential role for Substance P serum levels in monitoring intestinal inflammation in patients with inflammatory bowel disease.     

Urinary copper excretion before and after oral intake of d-penicillamine in parents of patients with Wilson's disease

BackgroundUrinary copper excretion higher than 100 μg/24 h is useful for diagnosing Wilson's disease. d-Penicillamine challenge test may produce higher levels than 1400 μg/24 h, allowing for better diagnostic accuracy. This study investigated whether heterozygotes reach this value and compared copper serum levels, ceruloplasmin, and urinary copper excretion before and after administering d-penicillamine to the parents of Wilson's disease patients.MethodsFifty parents of adult patients were enrolled to obtain copper serum levels and ceruloplasmin along with 24-h urinary copper excretion before and after administering 1 g d-penicillamine.ResultsSerum ceruloplasmin and copper levels were significantly lower in fathers than in mothers (mean 21.8 × 27.8 mg%; 71.4 × 88.0 μg%; p ≤ 0.001). The mean of basal 24-h urinary copper excretion was higher in fathers (26.2 × 18.7 μg/24 h, p = 0.01), but did not differ between the genders after d-penicillamine (521.7 × 525.3, range 31.6–1085.1 μg/24 h, p = 0.8).ConclusionsThe mean values of serum copper, ceruloplasmin, and basal urinary copper excretion were different between males and females. The current diagnostic threshold of 24-h urinary copper excretion after d-penicillamine was not reached by heterozygotes. The increased urinary copper excretion after d-penicillamine challenge was much higher than fivefold the upper limit of normal urinary copper excretion in the majority of heterozygotes and should not be taken into account when diagnosing Wilson's disease.     

Prognostic value of increased B type natriuretic peptide in cases with acute pancreatitis

BackgroundAcute pancreatitis (AP) is a systemic disease with a rising incidence. Cardiac dysfunction may occur as an early complication of AP. B type natriuretic factor (BNP) is a diagnostic and prognostic indicator of cardiac disorders. Therefore, in this study we aimed to assess the relationship between serum BNP concentrations and severity of AP.MethodsPatients with AP who were admitted to gastroenterology clinic of our center, were included in this study. BNP measurements were performed twice, once on admission to the hospital and another after clinical and laboratory remission of the disease. All patients underwent echocardiography, abdominal ultrasonography and/or computed tomography chest X-ray and routine biochemical assays. Disease severity was determined by Ranson, Balthazar and Glasgow scoring systems.ResultsA total of 55 patients with AP (33 male, 60%) were enrolled in the study. Causes of AP were biliary in 32 patients (58%), alcoholic in 10 (18%), idiopathic in 8 (15%), hyperlipidemic in 4 (7%) and ERCP related in one patient (2%), respectively. Serum BNP levels in first 2 days of admission and after the clinical and laboratory remission of disease were 444 ± 295.9 and 124 ± 109.5 pg/ml, respectively (p < 0.001). Increased serum BNP levels were positively correlated with severity of the disease (p < 0.001). We could not find a difference between serum BNPe levels of edematous and necrotizing patients (P = 0.683).ConclusionIncreased serum BNP levels might be a plausible indicator of severity of AP during the course of the disease.     

Copper Deficiency After Gastric Surgery: A Reason for Caution

BackgroundAcquired copper deficiency in adults leads to hematological and neurological manifestations that mimic vitamin B12 deficiency. A significant number of patients with copper deficiency syndrome have a history of gastric surgery, often remote. We sought to determine whether copper deficiency is present in a population of individuals with longstanding partial gastric resection.MethodsSerum copper, ceruloplasmin, and zinc levels were determined in 20 patients with a history of partial gastric resection and 50 controls, randomly selected from the Oklahoma City Veterans Affairs Medical Center electronic database.ResultsHypocupremia and symptoms of copper deficiency were detected in patients with partial gastric resection in contrast to controls (3/20 versus 0/50, P = 0.02). Serum copper and ceruloplasmin levels were significantly lower in individuals with partial gastric resection than in controls (P = 0.04 and P = 0.001, respectively). The mean interval between gastric surgery and testing was 20.7 years.ConclusionsOur results indicate that a significant number of individuals with longstanding history of partial gastric resection have undiagnosed hypocupremia. Screening for copper deficiency after gastric surgery may prevent the development of hematological and neurological complications in these patients.     

Serum hepcidin concentrations correlate with ferritin in patients with inflammatory bowel disease

Background and aimsAnemia is a frequent complication of inflammatory bowel disease (IBD). Hepcidin, a key mediator in this anemia, is up-regulated by high iron levels and inflammation, and serum levels are elevated in IBD. However, the extent of inflammatory activity and iron deficiency for the regulation of hepcidin is not known. This study aimed to evaluate serum hepcidin levels in anemic and non-anemic IBD patients, with iron or non-iron deficiency, and active or inactive disease.MethodsThis retrospective, observational study analyzed serum hepcidin levels from 247 patients with IBD (130 Crohn's patients and 117 with ulcerative colitis) recruited at Swiss Inflammatory Bowel Disease Cohort Study centers. Patients were divided into 5 different groups using criteria of active and inactive diseases (C-reactive protein, and CDAI/MTWAI = disease activity-index), anemia (hemoglobin) and iron deficiency (ferritin) and compared to healthy controls with no signs of anemia and normal ferritin levels. Hepcidin was measured using enzyme-linked immunosorbent assay.ResultsIndependent of inflammatory activity, all patients with decreased ferritin (< 30 μg/L) had significantly lower hepcidin levels when compared to patients and healthy controls having normal ferritin (> 30 μg/L). A significant correlation between serum ferritin levels and serum hepcidin was found (Spearman's Rho = 0.491; p < 0.001). A backward multi-linear stepwise regression analysis showed that only ferritin, and none of the inflammatory markers or age and sex correlated significantly (p = 0.005) with hepcidin.ConclusionThis retrospective analysis suggests that iron deficiency is the key trigger for hepcidin regulation in IBD patients with anemia.     

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.     

Serum BLyS and APRIL as possible indicators of disease activity in pediatric systemic lupus erythematosus and juvenile idiopathic arthritis

Aim of the workTo assess serum levels of B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) to determine their correlations with disease activity in pediatric systemic lupus erythematosus (pSLE) and juvenile idiopathic arthritis (JIA) patients.Patients and methodsTwenty-nine pSLE patients and 33 JIA patients were recruited. SLE disease activity was assessed using the systemic lupus erythematosus disease activity index (SLEDAI), while the juvenile arthritis 27 joint disease activity score (JADAS-27) was calculated for JIA patients. Serum samples were assayed for BLyS and APRIL by the enzyme linked immunosorbent assay (ELISA).ResultsSerum BLyS and APRIL were elevated in both pSLE and JIA patients compared to controls. Serum BLyS levels correlated with both SLE and JIA disease activity (p = 0.042, p = 0.019, respectively) whereas serum APRIL levels correlated positively with JADAS-27 and inversely with SLEDAI (p = 0.001, p = 0.02, respectively). Elevated serum BLyS and APRIL were significantly associated with a lower incidence of nephritis (p = 0.043, p = 0.016, respectively), while elevated serum APRIL significantly associated with negative anti-dsDNA in pSLE patients (p = 0.017). In JIA patients, both serum BLyS and APRIL were significantly associated with the presence of ANA (p = 0.008, p < 0.001, respectively), while high serum APRIL associated with the presence of RF (p = 0.035). APRIL and BLYS levels correlated with each other positively in JIA but inversely in pSLE patients.ConclusionSerum BLyS showed elevated levels that correlated significantly with pSLE and JIA disease activity, accordingly anti-BLyS therapy might be of great benefit to offset disease flare. The inverse correlations observed between APRIL with both BLyS and disease activity in pSLE patients raises the possibility of being a down regulator of the disease process.     

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.     

A prospective evaluation of the predictive value of faecal calprotectin in quiescent Crohn's disease

BackgroundFaecal calprotectin (FC) is a non-invasive marker of gastrointestinal inflammation.AimTo determine whether higher FC levels in individuals with quiescent Crohn's disease are associated with clinical relapse over the ensuing 12 months.MethodsA single centre prospective study was undertaken in Crohn's disease patients in clinical remission. The receiver operating characteristic (ROC) curve for the primary endpoint of clinical relapse by 12 months, based on FC at baseline, was calculated. Kaplan–Meier curves of time to relapse were based on the resulting optimal FC cutoff for predicting relapse.ResultsOf 97 patients recruited, 92 were either followed up for 12 months without relapsing, or reached the primary endpoint within that period. Of these, 10 (11%) relapsed by 12 months. Median FC was lower for non-relapsers, 96 μg/g (IQR 39–237), than for relapsers, 414 μg/g (IQR 259–590), (p = 0.005). The area under the ROC curve to predict relapse using FC was 77.4%. An optimal cutoff FC value of 240 μg/g to predict relapse had sensitivity of 80.0% and specificity of 74.4%. Negative predictive value was 96.8% and positive predictive value was 27.6%, FC ≥ 240 μg/g was associated with likelihood of relapse by 12-months 12.18 (95%CI 2.55–58.2) times higher than lower values (p = 0.002).ConclusionsIn this prospective dataset, FC is a useful tool to help identify quiescent Crohn's disease patients at a low risk of relapse over the ensuing 12 months. FC of 240 μg/g was the optimal cutoff in this cohort.     

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     

Serum copper as a marker of inflammation in prediction of short term outcome in high risk patients with chronic heart failure

BackgroundOxidative process and inflammation are regarded as important factors in the pathogenesis of chronic heart failure. Our study was aimed at investigating the prognostic value of serum copper levels in high risk subjects with chronic heart failure.MethodsSerum copper levels and other prognostic indicators were determined in the group of 60 patients with chronic heart failure due to ischemic heart disease: 30 consecutive subjects with acute decompensation of chronic heart failure (acute group A) and 30 patients with chronic stable heart failure (group B). Patients were followed prospectively 12 months. Primary end-point was the mean time to death and/or heart failure hospital admission.ResultsThe mean time to death was in the group A 279.4 ± 18.9 days and 351.7 ± 13.6 days in the group B (p < 0.0001). Cox proportional hazard model revealed that the time to death for all subjects (n = 60) was affected by cardiothoracic ratio (p < 0.001). The time to combined end-point death or hospital admission was affected by serum copper concentration (p < 0.0001).ConclusionSerum copper levels predicted short term outcome in high risk patients with chronic heart failure.     

Efficacy,tolerability, and predictors of response to infliximab therapy for Crohn's disease: A large single centre experience

BackgroundInfliximab is licenced for use in Crohn's disease (CD). Trial data demonstrate that infliximab is effective for inducing remission of active CD, healing fistulising CD, and preventing relapse once in remission. However, long-term data regarding efficacy, safety, and predictors of response are still emerging.AimTo examine these issues in a large cohort of patients who received infliximab for CD.MethodsA retrospective analysis of prospectively collected data was performed for 210 patients receiving infliximab for luminal or fistulising CD. Response to infliximab induction therapy, and sustained clinical benefit, were assessed by a decrease in Harvey–Bradshaw Index (HBI) of ≥2 points. Remission was defined as an HBI ≤ 4. Physician's global assessment was used where HBI could not be obtained. Demographic and disease factors that may predict response to therapy were analysed by Kaplan–Meier plots and univariate and multivariate analyses.ResultsOverall, 173 (82.4%) patients responded to infliximab induction, with 114 (65.9%) achieving sustained clinical benefit. Almost 40% of the study cohort had an HBI ≤ 4, indicating remission, at last point of follow-up (median 24 months). Concomitant immunosuppression predicted sustained clinical benefit in the first 6 months of therapy (P = 0.03). An inflammatory disease phenotype (P = 0.04 univariate analysis, P = 0.03 Kaplan Meier analysis) and male gender (P = 0.03) also predicted sustained clinical benefit. Episodic therapy was associated with an increased likelihood of secondary non-response. Adverse events, including malignancies, were few.ConclusionIn this single centre study, infliximab was efficacious and well-tolerated in CD.     

Acute histological inflammatory activity is associated with clinical relapse in patients with ulcerative colitis in clinical and endoscopic remission

BackgroundIt has been suggested that acute histological activity has a prognostic value in the outcome of ulcerative colitis (UC) patients in clinical and endoscopic remission. Our aim was to assess the role of histology as a risk factor for clinical relapse (CR) in patients in both clinical and endoscopic remission.MethodsPatients with left-sided or extensive UC in clinical and endoscopic remission (Mayo endoscopic subscore ≤1) undergoing colonoscopy for dysplasia surveillance with random colonic biopsies between 2005–2015 were included. Basal plasmacytosis, acute (AHA), and the chronic (CHA) histological inflammatory activity of all biopsy sets were evaluated.ResultsOne hundred and thirteen patients were included. Median time in clinical remission at inclusion was 27 months (IQR 15–56). Eight percent of patients relapsed within the first year and 33% during the whole follow-up period. In the univariate analysis, the presence of AHA, alone (P = 0.048) or together with a past flare within the previous 12 months (P = 0.01), was associated with CR within the first year of follow-up. In the multivariate analysis, AHA, together with a flare within the previous 12 months, remained the only risk factor for relapse (RR = 7.5; IC95%; 1.8–29.9; P = 0.005).ConclusionsIn UC patients in clinical and endoscopic remission, the presence of AHA is a risk factor for clinical relapse.     

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.     

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.