Stephan Schleder

Association of the novel serologic anti-glycan antibodies anti-laminarin and anti-chitin with complicated Crohn's disease behavior.

Background: We tested a panel of novel serological anti‐glycan antibodies including the previously unpublished anti‐laminarin IgA (Anti‐L) and anti‐chitin IgA (Anti‐C) carbohydrate antibodies for the presence in Crohns disease (CD) patients, diagnosis and differentiation of CD, association with complicated disease behavior, and marker stability over time. Methods: The presence of Anti‐L, Anti‐C, anti‐chitobioside IgA (ACCA), anti‐laminaribioside IgG (ALCA), anti‐mannobioside IgG (AMCA), and anti‐Saccaromyces cervisiae IgG (gASCA) carbohydrate antibodies were tested in serum samples from 824 participants (363 CD, 130 ulcerative colitis [UC], 74 other gastrointestinal diseases, and 257 noninflammatory bowel/gastrointestinal disease controls) of the German IBD‐network by enzyme‐linked immunosorbent assay (ELISA; Glycominds, Lod, Israel) and for perinuclear antineutrophil cytoplasmic antibody (pANCA) by immunofluorescence. Results: In all, 77.4% of the CD patients were positive for at least 1 of the anti‐glycan antibodies. gASCA or the combination of gASCA/pANCA remained most accurate for the diagnosis of CD, but the combined use of the antibodies improved differentiation of CD from UC. Several single markers as well as an increasing antibody response were independently linked to a severe disease phenotype, as shown for the occurrence of complications, CD‐related surgery, early disease onset, and ileal disease location. This was observed for both quantitative and qualitative antibody responses. The antibody status remained stable over time in most IBD patients. Conclusions: A panel of anti‐glycan antibodies including the novel Anti‐L and Anti‐C may aid in differentiation of CD from UC, is associated with complicated CD behavior and IBD‐related surgery, and is stable over time in a large patient cohort. Inflamm Bowel Dis 2009

Serum anti-glycan antibodies predict complicated Crohn's disease behavior: A cohort study†

Background: A high proportion of patients with Crohns disease (CD) over time develop complications like fistulae and strictures, requiring surgery. We tested a panel of antiglycan antibodies for predicting the occurrence of complications and CD‐related surgery in an adult patient cohort. Methods: Serum samples of 149 CD patients of the German inflammatory bowel disease (IBD) network were tested for the presence of anti‐laminarin IgA (Anti‐L), anti‐chitin IgA (Anti‐C), anti‐chitobioside IgA (ACCA), anti‐laminaribioside IgG (ALCA), anti‐mannobioside IgG (AMCA), and anti‐Saccaromyces cerevisiae IgG (gASCA) carbohydrate antibodies by enzyme‐linked immunosorbent assay (ELISA) (IBDX® panel, Glycominds, Lod, Israel) in a blinded fashion. Clinical data were available on occurrence of complicated disease or CD‐related surgery as well as disease activity, onset, and location. Results: The median follow‐up of the patients without any previous complication or surgery at time of sample procurement was 53.7 months. Overall, 26.3% developed a complication and 17.1% underwent CD‐related surgery, respectively. Positivity for gASCA, AMCA, ACCA, and Anti‐L alone or an increasing frequency of positive serum antibodies independently predicted a faster progression toward a more severe disease course. Once a complication or surgery had occurred only positivity for Anti‐L or more than 3 markers out of the whole panel indicated progression to an additional surgery or complication. The antibody status of most patients remained stable over time. Conclusions: This is the first study showing the clinical value of serum antiglycan antibodies for prediction of a more complicated disease course in adult patients with CD. (Inflamm Bowel Dis 2010)

Dynamic magnetic resonance defecography in 10 asymptomatic volunteers

AIM Evaluation of the wide range of normal findings in asymptomatic women undergoing dynamic magnetic resonance (MR) defecography. METHODS MR defecography of 10 healthy female volunteers (median age: 31 years) without previous pregnancies or history of surgery were evaluated. The rectum was filled with 180 mL gadolinium ultrasound gel mixture. MR defecography was performed in the supine position. The pelvic floor was visualized with a dynamic T2-weighted sagittal plane where all relevant pelvic floor organs were acquired during defecation. The volunteers were instructed to relax and then to perform straining maneuvers to empty the rectum. The pubococcygeal line (PCGL) was used as the line of reference. The movement of pelvic floor organs was measured as the vertical distance to this reference line. Data were recorded in the resting position as well as during the defecation process with maximal straining. Examinations were performed and evaluated by two experienced abdominal radiologists without knowledge of patient history. RESULTS Average position of the anorectal junction was located at -5.3 mm at rest and -29.9 mm during straining. The anorectal angle widened significantly from 93° at rest to 109° during defecation. A rectocele was diagnosed in eight out of 10 volunteers showing an average diameter of 25.9 mm. The bladder base was located at a position of +23 mm at rest and descended to -8.1 mm during defecation in relation to the PCGL. The bladder base moved below the PCGL in six out of 10 volunteers, which was formally defined as a cystocele. The uterocervical junction was located at an average level of +43.1 mm at rest and at +7.9 mm during straining. The uterocervical junction of three volunteers fell below the PCGL; described formally as uterocervical prolapse. CONCLUSION Based on the range of standard values in asymptomatic volunteers, MR defecography values for pathological changes have to be re-evaluated.

Characterization of Changes in Serum Anti-Glycan Antibodies in Crohn's Disease – a Longitudinal Analysis

Introduction Anti-glycan antibodies are a promising tool for differential diagnosis and disease stratification of patients with Crohns disease (CD). We longitudinally assessed level and status changes of anti-glycan antibodies over time in individual CD patients as well as determinants of this phenomenon. Methods 859 serum samples derived from a cohort of 253 inflammatory bowel disease (IBD) patients (207 CD, 46 ulcerative colitis (UC)) were tested for the presence of anti-laminarin (Anti-L), anti-chitin (Anti-C), anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside (AMCA) and anti-Saccharomyces cerevisiae (gASCA) antibodies by ELISA. All patients had at least two and up to eleven serum samples taken during the disease course. Results Median follow-up time for CD was 17.4 months (Interquartile range (IQR) 8.0, 31.6 months) and for UC 10.9 months (IQR 4.9, 21.0 months). In a subgroup of CD subjects marked changes in the overall immune response (quartile sum score) and levels of individual markers were observed over time. The marker status (positive versus negative) remained widely stable. Neither clinical phenotype nor NOD2 genotype was associated with the observed fluctuations. In a longitudinal analysis neither changes in disease activity nor CD behavior led to alterations in the levels of the glycan markers. The ability of the panel to discriminate CD from UC or its association with CD phenotypes remained stable during follow-up. In the serum of UC patients neither significant level nor status changes were observed. Conclusions While the levels of anti-glycan antibodies fluctuate in a subgroup of CD patients the antibody status is widely stable over time.

Clinical utility of anti‐glycan antibodies in pediatric crohn's disease in comparison with an adult cohort

Background: We tested a panel of serological anti‐glycan antibodies including the novel anti‐laminarin (Anti‐L) and anti‐chitin (Anti‐C) antibodies in pediatric Crohns disease (CD) patients for diagnosis of CD and association with complicated CD behavior. In addition, we compared this panel in pediatric CD with adult CD patients for possible changes in accuracy over time. Methods: Anti‐L, Anti‐C, anti‐chitobioside (ACCA), anti‐laminaribioside (ALCA), anti‐mannobioside (AMCA), and anti‐Saccaromyces cervisiae (gASCA) antibodies were tested in serum samples of 131 pediatric participants (59 CD, 27 ulcerative colitis [UC], and 45 noninflammatory bowel disease [IBD] controls) with enzyme‐linked immunosorbent assay (ELISA). The results were compared to an adult cohort of 728 participants (355 CD, 129 UC, and 244 non‐IBD controls). Results: In all, 78% of the pediatric CD patients were positive for at least one of the anti‐glycan antibodies. gASCA was most accurate for the diagnosis of CD, but combined use of the antibodies improved differentiation of CD from UC. gASCA, AMCA, ALCA, or Anti‐L and an increasing antibody level were independently linked to complicated CD behavior, CD‐related surgery, and ileal disease location (odds ratio 3.9–8.7). Considering the age at sample procurement the accuracy of the markers compared to an adult cohort remained stable for the differentiation of CD versus UC as well as for the association with complications, CD‐related surgery, and ileal disease involvement. Conclusions: A panel of anti‐glycan antibodies including the novel Anti‐L and Anti‐C may aid in the differentiation of pediatric CD from UC and is associated with complicated CD behavior. The marker accuracy remained constant over time. (Inflamm Bowel Dis 2011;)

Preoperative differentiation of thyroid adenomas and thyroid carcinomas using high resolution contrast-enhanced ultrasound (CEUS)

BACKGROUND To evaluate the impact of high-resolution contrast-enhanced ultrasound (CEUS) in combination with Color Coded and Power Doppler Sonography (CCDS/PD) in the preoperative differentiation of thyroid adenomas and thyroid carcinomas. METHODS A total of 101 patients (55 female, median age 54 years) underwent surgery for thyroid adenoma and thyroid carcinoma. CCDS/PD and CEUS were performed in all patients by an experienced examiner using a multifrequency linear transducer (6-9 or 6-15 MHz) and were digitally stored. Reading of the ultrasound images was performed by two experienced radiologists in consensus. A histopathological evaluation was obtained as standard of reference in all patients. RESULTS Altogether, 75 thyroid adenomas and 26 thyroid carcinomas were detected. Mean diameter of thyroid adenomas and thyroid carcinomas was 27 mm and 32 mm, respectively. The differences in microcirculation of thyroid adenomas and thyroid carcinomas were statistically highly significant (p <  0.01). Representative features for thyroid adenomas were either no wash-out or wash-out with persisting edge in late phase, for thyroid carcinomas a complete wash-out in late phase. Thus, a calculation of sensitivity, specificity, positive and negative predictive value of 81% , 92% , 97% and 63%, respectively, for the differentiation of benignity and malignancy was possible. CONCLUSIONS Dynamic evaluation of microcirculation using CEUS and CCDS/PD enables a more reliable preoperative discrimination between thyroid adenomas and thyroid carcinomas.

Hemoglobin and hematocrit levels in the prediction of complicated Crohn's disease behavior--a cohort study.

Background Markers that predict the occurrence of a complicated disease behavior in patients with Crohns disease (CD) can permit a more aggressive therapeutic regimen for patients at risk. The aim of this cohort study was to test the blood levels of hemoglobin (Hgb) and hematocrit (Hct) for the prediction of complicated CD behavior and CD related surgery in an adult patient population. Methods Blood samples of 62 CD patients of the German Inflammatory Bowel Disease-network “Kompetenznetz CED” were tested for the levels of Hgb and Hct prior to the occurrence of complicated disease behavior or CD related surgery. The relation of these markers and clinical events was studied using Kaplan-Meier survival analysis and adjusted COX-proportional hazard regression models. Results The median follow-up time was 55.8 months. Of the 62 CD patients without any previous complication or surgery 34% developed a complication and/or underwent CD related surgery. Low Hgb or Hct levels were independent predictors of a shorter time to occurrence of the first complication or CD related surgery. This was true for early as well as late occurring complications. Stable low Hgb or Hct during serial follow-up measurements had a higher frequency of complications compared to patients with a stable normal Hgb or Hct, respectively. Conclusions Determination of Hgb or Hct in complication and surgery naïve CD patients might serve as an additional tool for the prediction of complicated disease behavior.

Diagnostic value of a hand-carried ultrasound device for free intra-abdominal fluid and organ lacerations in major trauma patients

Background Technological progress has led to the introduction of hand-carried ultrasound (HCU) imagers in clinical workflow. The aim of this study is to analyse whether examination with a HCU device is a rapid and reliable alternative to contrast-enhanced multidetector CT (MDCT) scans in diagnosis of free intra-abdominal fluid and organ lacerations in major trauma patients. Methods 31 major trauma patients with an injury severity score >15 and the necessity of a MDCT scan (standard of reference) were enrolled prospectively to this study, and additionally examined with a HCU, according to ‘focused assessment with sonography for trauma’ principles for the assessment of organ lacerations and free intra-abdominal fluid. The HCU device employed was of the latest generation. Statistical analysis was performed using PASW V.18. Results Four patients were diagnosed with free intra-abdominal fluid (prevalence 12.9%). HCU showed a sensitivity and specificity of 75% and 100%, respectively. Positive predictive value and negative predictive value were 100% and 96%, respectively. Five patients had organ lacerations (prevalence 16.1%). In these cases, the HCU was able to detect organ lacerations with a sensitivity and specificity of 80% and 100%, respectively. Therefore, a positive predictive value and negative predictive value of 100% and 96%, respectively, were calculated. Conclusion In major trauma patients, examination with HCU according to the ‘focused assessment with sonography for trauma’ principles for the diagnosis of organ lacerations and free intra-abdominal fluid is a reliable and rapid alternative to MDCT scans and can help save precious time in emergency situations, and should, additionally, be evaluated in the pre-clinical workflow.

Interobserver Agreement in MR Enterography for Diagnostic Assessment in Patients with Crohn's Disease

PURPOSE To evaluate the extent to which MRE can be used as an observer-independent, objective imaging method for the diagnosis and evaluation of CD with respect to the detection of inflammatory changes of the small bowel and lymphadenopathy as diagnostic criterion and bowel distension as a quality criterion. MATERIALS AND METHODS MRE scans of 84 patients (42 female, median age 37 years) were evaluated independently by 4 experienced radiologists. Analysis of inflammatory changes of the bowel wall, lymphadenopathy and adequate bowel distension was conducted separately for the jejunum, ileum and terminal ileum. The Kendalls W-test was used for the statistical comparison of concordance. RESULTS In a total of 55 patients, inflammatory activity of the bowel wall was detected and MRE was found to have a high interobserver reproducibility concerning inflammatory changes of the intestinal wall (Kendalls W 0.527 - 0.823). Concerning lymphadenopathy (31 cases, 36.9 %), a low to moderate consensus could be shown with a Kendalls W value of 0.402 - 0.505. For the assessment of adequate bowel distension, a moderate concordance between the operators could be found (Kendalls W 0.497 - 0.581). CONCLUSION MRE has proven high interobserver agreement with respect to the diagnosis of inflammatory disease activity of the bowel as a diagnostic criterion in patients with CD. Concerning adequate bowel distension as a quality criterion of the examination itself and lymphadenopathy as a diagnostic criterion, moderate interobserver agreement could be found. This is thought to have a rather small effect on the diagnostic significance and conclusiveness of the method in the daily routine. KEY POINTS ▶ MR enterography as observer independent diagnostic procedure in patients with Chrons Disease. ▶ Highest interobserver concordance for the criterion of inflammatory bowel wall affection. ▶ Moderate interobserver concordance for lymphadenopathy and bowel distension.

Preoperative diagnosis of thyroid adenomas using high resolution contrast-enhanced ultrasound (CEUS)

To evaluate the impact of high-resolution contrast-enhanced ultrasound (CEUS), Color Coded and Power Doppler Sonography (CCDS/PD), in the preoperative recognition of thyroid adenomas. A total of 64 patients (36 female, median age 54 years) underwent surgery for thyroid adenoma. CEUS with linear multifrequency probes (6-9 or 6-15 MHz) and CCDS/PD was performed in all patients preoperatively by an experienced examiner and images were stored in PACS. Reading of the ultrasound images was performed in consensus by two experienced radiologists. Histopathology was achieved as standard of reference in all patients. Median diameter of the tumor lesions was 27 mm. 31 nodules were found on the left side. In B-Scan mode 13 (20%) adenomas showed complex cystic echo pattern and 44 (69%) had a complete and sharp hypoechoic edge. 43 (67%) thyroid adenomas had strong hypervascularization in CCDS/PD. In 61 (95%) adenomas early contrast enhancement was present in CEUS and 50 (78%) adenomas proved no wash-out or central wash-out with persisting edge enhancement. In 47 (73%) cases early contrast enhancement was combined with no washout or with central wash-out with persisting edge enhancement. 45 (70%) thyroid lesions had preoperatively been classified as benign lesions correctly. Dynamic evaluation of microcirculation by CEUS and CCDS/PD enables a more reliable preoperative characterization of thyroid adenomas.