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ABSTRACT: BACKGROUND & AIMS: The European Society for Pediatric Gastroenterology and Nutrition proposed guidelines for the diagnosis of celiac disease, stating that duodenal biopsy is no longer needed if patients have symptoms and levels of immunoglobulin A anti-tissue transglutaminase (IgA anti-tTG) more than 10-fold the cutoff value. We evaluated the accuracy of this guideline in a well-characterized population using different commercial assays. METHODS: We analyzed levels of IgA anti-tTG in serum samples from 104 consecutive pediatric and adult patients who were not deficient in IgA and diagnosed with celiac disease from August 1, 2000 to December 31, 2009. We also analyzed serum samples from 537 consecutive patients without celiac disease (controls), collected from May 1, 2004 to October 12, 2006, who underwent intestinal biopsy analysis. Serum levels of antibodies were quantified using assays from BioRad, INOVA, Genesis, and Thermo Fisher. RESULTS: The likelihood ratio (probability of a specific result in patients divided by probability of the same result in controls) for celiac disease increased with levels of IgA anti-tTG in all assays. Depending on the assay, the likelihood ratio for levels >10-fold the cutoff ranged from 111 to 294. The percentage of patients with celiac disease with levels of IgA anti-tTG>10-fold the cutoff ranged from 41% to 61%, depending on the assay. For levels of anti-tTG>10-fold the cutoff, the post-test probabilities for celiac disease (probability of disease, based on pre-test probability and test result) were, depending on the assay, 89%-96% and 53%-75% (depending on the assay), for pre-test probabilities (probability of disease depending on symptoms) of 7% and 1%, respectively. CONCLUSIONS: To diagnosis celiac disease based on serologic factors, it might be best to define thresholds for levels of IgA anti-tTG based on a predefined likelihood ratio or post-test probability, instead of a multiple of a cutoff value. Patients with a high pre-test probability and levels of anti-tTG >10-fold the cutoff have a high probability for having celiac disease, aiding clinical decision making.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 10/2012; · 5.64 Impact Factor
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ABSTRACT: Different serologic tests are available for the diagnosis of celiac disease (CD).
To evaluate the diagnostic performance of anti-tissue transglutaminase (tTG) and anti-deamidated gliadin (DGP) for the serologic diagnosis of CD.
The study population consisted of 107 consecutive adult CD and 542 consecutive disease controls who underwent an intestinal biopsy. Samples were tested for total IgA, IgA anti-tTG, and IgG anti-DGP antibodies using assays from 2 manufacturers (INOVA and Thermo Fisher). Samples were also tested by a screening assay that simultaneously detects IgA and IgG antibodies to tTG and DGP (tTG/DGP screen) (INOVA).
Positivity for anti-DGP or anti-tTG had a likelihood ratio for CD that varied between 20 and 115, depending on the assay. Double positivity (positive for anti-tTG and anti-DGP) had the highest likelihood ratio (≥ 215) for CD. The likelihood ratios for single positivity (positivity for one assay combined with negativity for the other) had a likelihood ratio between 0.8 and 10.1. The likelihood ratio for CD was lowest (≤ 0.12) for double negative test results. Decision tree analysis revealed that determining IgA anti-tTG and IgG anti-DGP in all patients performed better than other serologic strategies.
The use of likelihood ratios improves the clinical interpretation of serologic testing for CD. Double positive test results had the highest likelihood ratio for CD, whereas double negative test results had the lowest likelihood ratio.
Clinica chimica acta; international journal of clinical chemistry 07/2012; 413(21-22):1761-7. · 2.54 Impact Factor
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Pieter Vermeersch,
Thomas Richter,
Almuthe C Hauer,
Martin Stern,
Holm H Uhlig,
Klaus-Peter Zimmer,
Martin W Laass,
Ilse Hoffman, Martin Hiele,
Thomas Mothes,
Xavier Bossuyt
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ABSTRACT: To evaluate whether taking into account anti-deamidated gliadin peptide (DGP) antibody concentrations improves clinical interpretation.
We calculated likelihood ratios (LR) using data from two previously published studies for assays from EUROIMMUN and INOVA.
LRs markedly increased with increasing IgG anti-DGP concentrations. LRs also increased with increasing IgA anti-DGP concentrations, although they were lower than for IgG anti-DGP.
Use of LRs for different test result intervals improves clinical interpretation.
Clinical biochemistry 10/2010; 44(2-3):248-50. · 2.02 Impact Factor
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ABSTRACT: Detection of IgG antibodies against deamidated gliadin peptides (DGP) is more sensitive and more specific for celiac disease than detection of IgG antibodies against native gliadin. Our aim was to evaluate the technical performance and diagnostic accuracy of four commercial IgG anti-DGP assays.
Commercial IgG anti-DGP assays from Euroimmun, Inova, Phadia and The Binding Site were evaluated and their diagnostic accuracy (sensitivity and specificity) compared to other serologic assays for celiac disease (3IgA and 2IgG anti-tTG assays, 1IgA and 1IgG anti-gliadin assay, 1IgA anti-DGP assay). The study population consisted of 86 consecutive CD patients and 741 disease controls.
The technical performance (linearity, interference and imprecision) of the IgG anti-DGP assays was acceptable. The sensitivity of the IgG anti-DGP assays varied between 76.7% and 86.0% at the cut-off recommended by the manufacturer and between 74.4% and 86.0% at the cut-off that corresponded to a specificity of 98%. The specificity varied between 97.3% and 99.3%. The diagnostic accuracy of the IgG anti-DGP assays was comparable to the diagnostic accuracy of the IgA anti-tTG assays. The sensitivity of the IgG anti-DGP assays was significantly better than sensitivity of the IgG anti-tTG assays (p<0.05) and the specificity was significantly better than the IgA and IgG anti-gliadin assays (p<0.05).
The overall performance of the four IgG anti-DGP assays was acceptable and the diagnostic accuracy comparable to the three IgA anti-tTG assays.
Clinica chimica acta; international journal of clinical chemistry 02/2010; 411(13-14):931-5. · 2.54 Impact Factor
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European Journal of Internal Medicine 10/2009; 20(6):e143-4. · 2.00 Impact Factor
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ABSTRACT: We investigated whether taking into account IgA anti-tissue transglutaminase antibody concentration (IgA anti-tTG) and total IgA concentration could improve clinical interpretation of serologic testing for celiac disease (CD).
We retrospectively identified 43 consecutive newly diagnosed CD patients and 545 consecutive disease control patients who had an IgA anti-tTG request during the 42-month study period and for whom intestinal biopsy results were available.
Sensitivity and specificity of the IgA anti-tTG assay from Genesis was 95.3% and 92.7%, respectively, with a likelihood ratio (LR) of 12.4. The LR for CD markedly increased with increasing IgA anti-tTG concentration (from 2.0 for results between 7 and 20 U/ml up to 319 for results >100 U/ml). The LR for CD was also higher in patients with a normal IgA concentration (0.82-4.53 g/L) compared to patients with an increased IgA concentration (15.3 vs. 3.1, respectively). These observations were confirmed with a second IgA anti-tTG assay from BioRad.
Sensitivity of IgA anti-tTG was good. Specificity, however, was reduced when IgA anti-tTG was weak positive or when the IgA concentration was increased. Taking into account IgA anti-tTG concentration and IgA concentration improves clinical interpretation of serologic testing for CD.
Clinica chimica acta; international journal of clinical chemistry 09/2009; 411(1-2):13-7. · 2.54 Impact Factor
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ABSTRACT: The study aim is to determine the relationship between the prevalence of colorectal cancer and iron status in elderly anemic and non-anemic patients.
We retrospectively investigated 359 consecutive elderly patients, aged 70 years and more, who presented to a geriatric department and who underwent a total colonoscopy. The histopathologic diagnosis of colorectal carcinoma was the primary outcome measure, and its presence was compared with the iron status, evaluated by serum ferritin and hemoglobin levels.
Less than half of the patients with colorectal carcinoma had iron-deficiency anemia. The prevalence of colorectal carcinoma was similar among patients with a serum ferritin level less than 50 microg/L (16%), between 50 and 100 mirog/L (20%), and greater than 100 microg/L (13%), and was not different between anemic and non-anemic patients. Sex (odds ratio for men 2.1; 95% confidence interval [CI], 1.2-3.9) and increasing age (6.6% per year; 95% CI, 1.2-12.4), but not hemoglobin and serum ferritin, were independent risk factors for colorectal carcinoma. Those with a proximal colorectal carcinoma had a lower hemoglobin and ferritin level and a higher prevalence of iron-deficiency anemia compared with patients with a distal colorectal carcinoma.
The prevalence of colorectal carcinoma is high in anemic and non-anemic elderly symptomatic patients, irrespective of the iron status. Therefore, the decision to order a colonoscopy in older patients should not only be considered in patients with anemia or iron deficiency but also in patients with suspicious symptoms without anemia or iron deficiency.
The American journal of medicine 01/2009; 121(12):1072-7. · 4.47 Impact Factor
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Paul Rutgeerts,
Gert Van Assche,
Séverine Vermeire,
Geert D'Haens,
Filip Baert,
Maja Noman,
Isolde Aerden,
Gert De Hertogh,
Karel Geboes, Martin Hiele,
Andre D'Hoore,
Freddy Penninckx
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ABSTRACT: Crohn's disease almost inevitably recurs after ileocolonic resection, and effective prophylactic therapy has not been identified. We investigated the efficacy and safety of ornidazole, a nitroimidazole antibiotic, for the prevention of clinical recurrence of Crohn's disease after curative ileocolonic resection in a placebo-controlled double-blind clinical trial.
Eighty patients were randomized to ornidazole 1 g/day or placebo started within 1 week of resection and continued for 1 year. The primary end point was the proportion of patients with clinical recurrence at 1 year. Secondary end points were endoscopic recurrence at 3 months and 12 months after resection.
Two patients in the ornidazole group withdrew consent and were not dosed. Ornidazole significantly reduced the clinical recurrence rate at 1 year from 15 of 40 (37.5%) patients in the placebo group to 3 of 38 (7.9%) patients in the ornidazole group (Fisher exact test, 8.03; P = .0046; odds ratio, 0.14; 95% confidence interval, 0.037-0.546). Ornidazole reduced endoscopic recurrence at 12 months from 26 of 33 (79%) in the placebo group to 15 of 28 (53.6%) in the ornidazole group (chi2 , 4.37; P = .037; odds ratio, 0.31; 95% confidence interval, 0.10-0.94). Endoscopic recurrence at 3 and 12 months predicted clinical recurrence. Significantly more patients in the ornidazole group dropped out from the study because of side effects (P = .041).
Ornidazole 1 g/day is effective for the prevention of recurrence of Crohn's disease after ileocolonic resection.
Gastroenterology 04/2005; 128(4):856-61. · 11.68 Impact Factor
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ABSTRACT: To determine the additional value of FDG-positron emission tomography (PET) to optimize delineation of the clinical target volume (CTV) in patients with advanced esophageal carcinoma.
The imaging and radiotherapy data from 30 patients with an advanced esophageal carcinoma were analysed. The lymph node classification for esophageal cancer was modified and translated into anatomical volumes on computed tomography (CT). The so defined 14 different regions were scored individually for lymph node involvement on CT, endoscopic ultrasound (EUS) and FDG-PET. The influence of discordant findings between conventional and functional imaging on the decision as to what should be irradiated was assessed.
In 14 of the 30 patients (47%) discordances were found in detection of the pathological lymph nodes between CT/EUS and FDG-PET. In 8 patients, 9 lymph node regions were found with pathologic nodes on conventional imaging only. In three of these patients the influence of FDG-PET findings would have led to a decrease of the irradiated volume. In 6 patients, 8 lymph node regions were found with a normal CT/EUS and pathologic nodes on FDG-PET. In three of these patients (10%) the influence of the FDG-PET would have led to enlargement of the irradiated volume.
The chance of a false negative result on FGD-PET is not negligible; therefore, the irradiated volume should not be reduced based on a negative FDG-PET in a region with suspect nodes on other investigations. However, due to the high specificity of FDG-PET enlarging the irradiated volume based on a positive FDG-PET in a region without suspected lymph nodes on CT and/or EUS should be considered. This indicates a role for FDG-PET in radiotherapy planning for esophageal cancer.
Radiotherapy and Oncology 01/2005; 73(3):269-75. · 5.58 Impact Factor
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ABSTRACT: Anti-tissue transglutaminase (tTG) assays that use human tTG as antigen have recently become available. We evaluated commercially available assays with human tTG antigen to estimate their diagnostic accuracies and to determine whether they agree sufficiently to be used interchangeably.
Ten commercially available second-generation anti-tTG assays were evaluated. The following populations were studied: celiac disease (CD) patients at the time of diagnosis without (n = 70) or with (n = 5) IgA deficiency; diseased controls (n = 70); and CD patients without (n = 28) or with (n = 2) IgA deficiency during follow-up. All individuals included in the study underwent intestinal biopsy. Technical performance (linearity, interference, precision, correlation, and agreement) and diagnostic accuracy (sensitivity and specificity) were compared. Anti-gliadin and anti-endomysium antibodies were also measured.
IgA anti-tTG results correlated well overall, but numerical values differed. Diagnostic sensitivity ranged between 91% and 97% and specificity between 96% and 100%. These were higher than the sensitivity and specificity of the IgA endomysium assay and the IgA gliadin assay. Generally, IgG anti-tTG was less sensitive but more specific than IgG anti-gliadin for the diagnosis of CD in the small group of IgA-deficient patients.
Overall diagnostic performance of IgA tTG assays is acceptable and comparable among the different assays, but numerical values differ. Standardization is needed.
Clinical Chemistry 12/2004; 50(11):2125-35. · 7.91 Impact Factor
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ABSTRACT: Iv cyclosporin A (CSA) is an effective therapy in patients with severe ulcerative colitis (UC). It remains unclear if this treatment affects the course of the disease in the long run. We investigated the long-term efficacy and safety in 86 patients with ulcerative colitis treated with i.v. CSA at our center.
The records of all patients treated with i.v. CSA between 11/1992 and 11/2000 were reviewed.
Seventy-two of 86 patients (83.7%) responded to i.v. CSA therapy, administered for a mean of 9 +/- 2 days. Following the initial treatment, 69 patients (96%) were discharged on oral CSA with mean blood CSA concentrations of 192 +/- 55 ng/mL. Azathioprine was added in 64 (89%) patients. A second treatment with CSA was necessary in 11 patients; 1 patient received three courses of i.v. treatment. The duration of follow-up averaged 773 +/- 369 days. Patients who were responders but were still having certain symptoms at discharge had a higher incidence of colectomy during follow-up. Of all initial responders, 18 (25%) underwent colectomy after a mean interval of 178 +/- 141 days. The life-table predicts that of all treated patients, 55% will avoid a colectomy during a period of 3 years. Complications of CSA treatment were mostly reversible, but 3 patients (3.5%) died of opportunistic infections (1 of Pneumocystis carinii pneumonia and 2 of Aspergillus fumigatus pneumoniae). One patient with anaphylactic shock caused by the CSA solvent was successfully resuscitated.
CSA is an effective treatment of the majority of patients with severe attacks of UC, although the toxicity and even mortality associated with its use necessitates careful evaluation, selection, and follow-up.
Inflammatory Bowel Diseases 04/2004; 10(2):73-8. · 4.86 Impact Factor
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ABSTRACT: Cyclosporine A is highly effective in severe attacks of ulcerative colitis (UC) but is associated with important adverse effects that are mainly dose dependent. Our single center, randomized, double-blind, controlled trial aimed to evaluate the additional clinical benefit of 4 mg/kg over 2 mg/kg IV cyclosporine in the acute treatment of severe UC.
Primary end point was the proportion of patients with a clinical response. Secondary end points included time to response, colectomy rate, and adverse effects.
Seventy-three patients were included. Day-8 response rates were 84.2% (32 of 38, 4 mg/kg) and 85.7% (32 of 35, 2 mg/kg) after a median of 4 days in both groups. Short-term colectomy rates were 13.1% (4 mg/kg) and 8.6% (2 mg/kg). Mean cyclosporine blood levels were 237 +/- 33 in the 2-mg/kg group and 332 +/- 43 ng/mL in the 4-mg/kg group. Active smoking was inversely correlated with clinical response (odds ratio, 0.06), but concomitant azathioprine or steroids were not predictive. A trend toward a higher incidence of hypertension was observed in the 4-mg/kg group (23.7% vs. 8.6%, 2 mg/kg, P < 0.08).
High-dose IV cyclosporine has no additional clinical benefit over low dose in the treatment of severe UC. Although we did not observe differences in adverse effects on the short term, the use of 2 mg/kg IV cyclosporine should provide an improved toxicity profile for medical treatment of severe UC.
Gastroenterology 10/2003; 125(4):1025-31. · 11.68 Impact Factor
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ABSTRACT: A randomized comparative study was conducted of injection therapy with epinephrine-polidocanol (1%) versus hemoclip application, versus injection combined with hemoclip for bleeding peptic ulcers.
One hundred five patients were randomized and 101 could be evaluated (46 had active spurting or oozing of blood; 55 a visible vessel). Patients were randomized to 1 of the 3 treatment modalities during endoscopy performed within 12 hours of admission. Endoscopy was repeated after 1 day or at recurrence of bleeding and before discharge. In case of recurrent bleeding, patients were retreated with the same modality.
Initial failure or the rate of early recurrence of bleeding was highest (but not statistically significant) in the hemoclip group (13/35; 37%), versus the injection (5/34; 15%) and combination (8/32; 25%) groups. Overall failure was significantly (p = 0.01) different among the 3 groups with the highest rate in the hemoclip group (12/35; 34%), versus the injection (2/34; 6%) and combination therapy (8/32; 25%) groups. The use of hemoclips alone appeared to fail because of difficulty with hemoclip placement and incomplete vessel compression. Complications included 1 perforation in the injection group and possibly 1 case of septic arthritis in the combination therapy group.
In this study, endoscopic treatment of bleeding peptic ulcers with the hemoclip was inferior overall to injection therapy.
Gastrointestinal Endoscopy 05/2002; 55(4):466-9. · 4.88 Impact Factor
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ABSTRACT: Intestinal transplantation (Itx) remains the most difficult form of transplantation. This is due to the high immunogenicity of the bowel that currently obligates Itx patients to heavy immunosuppression, which causes infection, posttransplant lymphoproliferative disease (PTLD), and drug toxicity. Wider application of Itx depends on the development of tolerogenic strategies to promote engraftment while reducing the need for immunosuppression. We applied a strategy to clinical Itx that combines intraportal donor-specific blood transfusion with a deliberately low immunosuppression protocol (no high-dose steroids; lower tacrolimus level).
A 55-year-old patient received a combined liver/Itx. Donor-specific whole blood was taken from the donor during procurement and transfused in the recipient portal vein after graft reperfusion. For induction immunosuppression, no intravenous bolus of steroids was given; only two doses of anti-interleukin 2 receptor antibody were administered. The patient received posttransplantation maintenance immunosuppression with lower tacrolimus levels than average (15 ng/ml first month; 5-10 ng/ml thereafter), low-dose azathioprine (1 mg/kg first to third months; 0.5 mg/kg thereafter), and low-dose steroids (Medrol 8 mg twice daily first and second months; 4 mg twice thereafter). The patient was monitored for rejection, graft-versus-host disease, infection, and PTLD. Protocol biopsy specimens were taken from the distal ileum (2 per week).
Clinical, endoscopic, and histologic signs of rejection did not develop. Chimerism was identified at day 28. Graft-versus-host disease was absent clinically. Chimerism was self-limiting and disappeared without modifying baseline immunosuppression and without observing a change in graft function. The patient remained free of systemic opportunistic infections, PTLD, and drug toxicity. Total parenteral nutrition was stopped at 7 weeks after transplantation. The patient remains free of total parenteral nutrition and free of rejection at 14 months after transplantation.
We describe an Itx patient who remained rejection free despite receiving significantly lower immunosuppression than average. We hypothesize that intraoperative immunomodulation via intraportal donor-specific blood transfusion in the absence of nonspecific overimmunosuppression promoted Itx acceptance.
Transplantation 04/2002; 73(6):966-8. · 4.00 Impact Factor
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ABSTRACT: To investigate permeability alterations of the macroscopically normal jejunum in Crohn's disease, the permeation of two probes was measured during perfusion of an isolated jejunal segment. The data were compared with the results obtained by the standard per oral test in the same patients. Test probes were PEG-400 and [51Cr]EDTA. Ten normal individuals, 12 patients with Crohn's ileitis or ileocolitis, and seven patients with isolated Crohn's colitis all with normal jejunum on x-ray series were studied. Upon perfusion of the proximal small bowel, the 3-hr [51Cr]EDTA excretion was significantly increased in ileitis patients (P=0.023) as compared to normals. The excretion exceeded the highest value of normals in eight of 12 ileitis patients. The excretion in Crohn's colitis patients was not significantly increased (P=0.24) and abnormal excretion was found only in one of the Crohn's colitis patients. PEG-400 permeation during perfusion did not differentiate between the groups, but five of the seven patients with isolated Crohn's colitis had PEG-400 excretion exceeding the highest value in normals. Overall, 13 of the 19 patients had increased permeation of one of the two probes through jejunal mucosa during perfusion. These data suggest that the permeability is increased in the majority of patients even in segments that seem normal on x-ray.
Digestive Diseases and Sciences 09/1994; 39(10):2170-2176. · 2.12 Impact Factor
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ABSTRACT: The metabolism of erythritol was assessed in six normal volunteers by measuring the amount of 13CO2 excretion and H2 excretion in breath, and erythritol in urine after intake of 25 g 13C-labelled erythritol. The results were compared with the same variables obtained after intake of 25 g 13C-labelled glucose and13C-labelled lactitol. In addition, the H2 production by faecal flora supplemented with small amounts of erythritol, glucose and lactitol was measured in vitro, as an index of bacterial metabolism of non-absorbed substrate. In contrast to the results obtained after intake of glucose and lactitol, no increase in breath 13CO2 and H2 was observed after intake of erythritol, and erythritol was nearly completely recovered in urine. The in vitro experiments showed that no H2 was formed by faecal flora from erythritol as compared with glucose and lactitol. It is concluded that erythritol is a substrate that is readily absorbed, and undergoes no metabolism by the host. If part of it escapes absorption, it is not metabolized by faecal flora.
The British journal of nutrition 12/1992; 69(01):169 - 176. · 3.45 Impact Factor
