Fecal calprotectin and platelet count predict histologic disease activity in pediatric ulcerative colitis: results from a projection-predictive feature selection.

Especially for pediatric patients, proxies of mucosal inflammation are needed. The Pediatric Ulcerative Colitis Activity Index (PUCAI) has been established to predict clinical and endoscopic disease activity. However, histologic inflammation might persist. We applied a special variable selection technique to predict histologic healing in pediatric ulcerative colitis (UC) as parsimoniously (but still as precisely) as possible. The retrospective analysis included data from two study cohorts, comprising 91 visits from 59 pediatric patients with UC. A Bayesian ordinal regression model was used in combination with a projection-predictive feature selection (PPFS) to identify a minimal subset of clinical and laboratory parameters sufficient for the prediction of histologic disease activity. Following the PPFS, CEDATA-GPGE patient registry data were analyzed to investigate the relevance of the selected predictors in relation to PUCAI and Physician Global Assessment (PGA) in up to 6697 patient visits. Fecal calprotectin (FC) and platelet count were identified as the minimal subset of predictors sufficient for prediction of histologic disease activity in pediatric UC. FC and platelet count also appeared to be associated with increasing disease activity as measured by PUCAI and PGA in the CEDATA-GPGE registry. Based on the selected model, predictions can be performed with a Shiny web app.  Conclusion: Our statistical approach constitutes a reproducible and objective tool to select a minimal subset of the most informative parameters to predict histologic inflammation in pediatric UC. A Shiny app shows how physicians may predict the histologic activity in a user-friendly way using FC and platelet count. To generalize the findings, further prospective studies will be needed. What is Known: • Histologic healing is a major endpoint in the therapy of ulcerative colitis (UC). • The PUCAI score has been established to predict disease activity in pediatric UC but is not suitable for the prediction of histologic healing. What is New: • Our Bayesian ordinal regression model in combination with a projection-predictive feature selection is a reproducible and objective tool to select the minimal subset of clinical and laboratory parameters to predict histologic inflammation in pediatric UC. • Histologic inflammation in pediatric UC can be non-invasively predicted based on the combination of fecal calprotectin levels and platelet count.

[The use of lipid containing nasal ointment for allergic rhinitis--a therapeutic option? A bicentric, prospective, open, randomised, controlled clinical study]. / Die Anwendung lipidhaltiger Nasensalbe bei allergischer Rhinitis--eine Therapieoption? Eine bizentrische, prospektive, offene, randomisierte, kontrollierte klinische Studie.

BACKGROUND: Some 10-20% of the population suffer from allergic rhinitis. A recently discussed and interesting, albeit disputed therapy option is the use of a lipid-based nasal ointment. METHOD: To test the efficacy of this nasal ointment as an adjuvant therapy for allergic rhinitis, a two-centre, prospective, open, randomized, controlled clinical study was carried out. RESULT: In the study, 17 patients using the test agent were compared with 16 who did not. For the group using the test agent, before and after comparisons showed a significant (about 40%) improvement in the medium, relative total range of symptoms (Wilcoxon-Mann-Whitney U-test, P<0.01) based on the individual parameters of sneezing attacks, nasal itching, nasal secretion and nasal obstruction. In the control group, non-use of the test agent meant that the total range of symptoms remained unchanged. No side effects were recorded. CONCLUSION: The test agent used in our study contains a lipid fraction, in this case in the form of high purity, long chain hydrocarbons. By local application, a significant improvement of the total symptomatology was shown. The mechanism has not been clarified. Owing to the efficacy and low risk of side effects, this seems to be a promising adjuvant therapy for allergic rhinitis. The probetoric use of this nasal ointment as a supportive therapeutic option should be reviewed in further clinical studies.

The Munich Barrett follow up study: suspicion of Barrett's oesophagus based on either endoscopy or histology only--what is the clinical significance?

BACKGROUND: The incidence of distal oesophageal adenocarcinoma is rising, with chronic reflux and Barrett's oesophagus being considered risk factors. Reliable detection of Barrett's oesophagus during upper endoscopy is therefore mandatory but requires both endoscopy and histology for confirmation. Appropriate management of patients with endoscopic suspicion but negative on histology, or vice versa, or of patients with no endoscopic suspicion but with a biopsy diagnosis of intestinal metaplasia at the gastro-oesophageal junction, has not yet been studied prospectively. PATIENTS AND METHODS: In a prospective multicentre study, 929 patients (51% male, mean age 50 years) referred for upper gastrointestinal endoscopy were included; 59% had reflux symptoms. The endoscopic aspect of the Z line and any suspicion of Barrett's oesophagus were noted, and biopsies were taken in all patients from the Z line (n = 4), gastric cardia (n = 2), and body and antrum (n = 2 each). Biopsies positive for specialised intestinal metaplasia (SIM) were reviewed by a reference pathologist for a final Barrett's oesophagus diagnosis. All patients with endoscopic and/or histological suspicion of Barrett's oesophagus were invited for a follow up endoscopy; the remaining cases (no endoscopic or histological suspicion of Barrett's oesophagus) were followed clinically. RESULTS: Of 235 patients positive for Barrett's oesophagus on endoscopy and/or histology, 63% agreed to undergo repeat endoscopy (mean follow up period 30.5 months). 46% of patients with an endoscopic Barrett's oesophagus diagnosis but no histological confirmation (group A) showed the same distribution, a further 42% did not have Barrett's oesophagus, and 11% had confirmed Barrett's oesophagus on both endoscopy and biopsy on follow up. In the group with a histological Barrett's oesophagus diagnosis but negative on initial endoscopy (group B), follow up showed the same in 26% whereas 46% had no Barrett's oesophagus, and confirmed Barrett's oesophagus (endoscopy plus histology) was diagnosed in 17%. Of the study population, 16 patients had Barrett's oesophagus on initial endoscopy confirmed by histology which remained constant in 70% at follow up (group C). Of the remaining patients without an initial Barrett's oesophagus diagnosis on either endoscopy or histology (group D) and only clinical follow up (mean follow up period 38 months), one confirmed Barrett's oesophagus case was found among 100 patients re-endoscoped outside of the study protocol. However, no single case of dysplasia or cancer of the distal oesophagus was detected in any patient during the study period. CONCLUSIONS: Even in a specialised gastroenterology setting, reproducibility of presumptive endoscopic or histological diagnoses of Barrett's oesophagus at follow up were poor. Only 10-20% of cases with either endoscopic or histological suspicion of Barrett's oesophagus had established Barrett's oesophagus after 2.5 years of follow up. The risk of dysplasia in this population was very low and hence meticulous follow up may not be required.

Endoscopic measurement of Barrett's esophagus length is unreliable - a prospective comparative biopsy study.

BACKGROUND AND AIMS: Endoscopic assessment of the length and area of Barrett's esophagus (BE) has become crucial in assessing its spontaneous course as well as any effect of pharmacological or endoscopic treatment. Little, however, is known about the extent to which the endoscopic assessment of BE length and area correlates with the histopathological confirmation of BE epithelium. PATIENTS AND METHODS: 75 consecutive patients (mean age 60 years; 58 men, 17 women) were included in a prospective study on the basis of the endoscopic suspicion of BE. BE was endoscopically defined as gastric-type epithelium between the proximal cardiac folds and the Z line, on moderate air insufflation. Stepwise four-quadrant biopsies (4QB) were then taken, beginning at the proximal cardiac folds and then every 2 cm up to the Z line. RESULTS: Among the 75 study patients, BE was histologically verified in 57 cases (group 1) and not confirmed in any of the endoscopic biopsy samples in 18 cases (group 2). In group 1, the mean difference between the endoscopic and histological assessment of BE length was + 1 cm (range 0 - 5 cm); when determining the BE area histologically from 4QB the mean difference to the endoscopic determination was + 36 % (range 0 - 93 %). These differences were independent of the presence and degree of hiatal hernia or the presence of long or short BE. CONCLUSIONS: In the majority of patients, there is only a moderate correlation between the endoscopic and the histological extent of BE. However, we also found a substantial individual variability in endoscopic-histological correlation; therefore studies on the effects of treatment on BE must consider both the endoscopic and histopathological BE lengths.

Bacteriobilia in percutaneous transhepatic biliary drainage: occurrence over time and clinical sequelae. A prospective observational study.

BACKGROUND: In the diagnosis and treatment of biliary disorders, establishing percutaneous transhepatic biliary drainage (PTBD) is an invasive procedure that can potentially lead to infectious complications in both the short and long-term. We therefore prospectively analysed the time course and spectrum of biliary bacteria in patients undergoing PTBD. METHODS: Forty-nine patients (19 F, 30 M; mean age 64 years) with malignant (65%) or benign (35%) biliary disorders were included, 20 of whom had a newly established PTBD (group A), while the remaining 29 had already had their PTBD in situ (group B) for a mean of 8 months. Bacteriological analyses of bile and blood were carried out, and clinical symptoms and laboratory values were obtained. RESULTS: Biliary bacteria were found in 60% of cases during the initial PTBD placement, and 24 h later this rate had already increased to 85%; two or more microorganisms were found in 40% initially and in 70% after a few days. At later PTBD exchanges, bacteriobilia was found in 100%, with all patients harbouring multiple organisms. Whereas the initial spectrum was mixed, Escherichia coli and enterococci (97% each), Klebsiella (73%) and Bacteroides species (37%) later predominated; Candida increased initially from 15% to 80%, but later decreased to 30%. Clinical signs of cholangitis were observed in 30% initially (no sepsis), but decreased to 6% at later exchanges. CONCLUSIONS: Bacteriobilia is initially a frequent, and later a regular, event in PTBD; however, clinically significant complications are rare during the long-term course and limited to the initial, more invasive, phase of PTBD. A knowledge of the bacterial spectrum is important for selecting appropriate antibiotic coverage if complications arise and/or major interventions such as surgery are planned.

Fatal outcome of lung transplantation in cystic fibrosis patients due to small-colony variants of the Burkholderia cepacia complex.

The aim of this study was to investigate the possible role of small-colony variant morphotypes of Burkholderia cepacia-like organisms in infectious complications in cystic fibrosis patients following lung transplantation. Respiratory tract specimens from 470 cystic fibrosis patients were screened over a 22-month period for Burkholderia cepacia-like organisms. Nineteen patients were positive for these organisms, eight of whom harboured small-colony-variant morphotypes. Three patients underwent bilateral lung transplantation during the study, two of whom harboured small-colony variants in addition to clonally identical wildtypes of Burkholderia multivorans and Burkholderia cepacia genomovar III prior to lung transplantation. Both patients developed fatal systemic infections post transplantation due to small-colony variants. In vitro testing revealed that small-colony variants exhibited increased serum resistance in comparison to wildtypes. The results of this study indicate that diagnostic efforts should be undertaken to carefully identify small-colony variants of Burkholderia cepacia complex, since they might be an indicator of poor post-transplantation outcome in patients with cystic fibrosis.