Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease

peer reviewedOBJECTIVES: The use of monoclonal anti-tumor necrosis factor (TNF) antibodies (infliximab, Remicade) is a new therapeutic approach for severe refractory luminal or fistulizing, Crohn's disease (CD). However, up to 30% of patients do not respond to this treatment. So far, no parameters predictive of response to anti-TNT have been identified. Our aim was to determine whether serological markers ASCA (anti-Saccharomyces cerevisiae antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibodies) could identify Crohn's patients likely to benefit from anti-TNF therapy. METHODS: Serum samples of 279 CID patients were analyzed for ASCA and pANCA before anti-TNF therapy. A blinded physician determined clinical response at week 4 (refractory luminal CD) or week 10 (fistulizing CD) after the first infusion of infliximab (5 mg/kg). RESULTS: Overall, there was no relationship between ASCA or pANCA and response to therapy. However, lower response rates were observed for patients with refractory intestinal disease carrying the pANCA+/ASCA- combination, although this lacked significance (p = 0.067). CONCLUSIONS: In this cohort of infliximab-treated patients, neither ASCA nor pANCA could predict response to treatment. However, the combination pANCA+/ASCA- might warrant further investigation for its value in predicting nonresponse in patients with refractory luminal disease

ESPEN guidelines on definitions and terminology of clinical nutrition

BACKGROUND: A lack of agreement on definitions and terminology used for nutrition-related concepts and procedures limits the development of clinical nutrition practice and research. OBJECTIVE: This initiative aimed to reach a consensus for terminology for core nutritional concepts and procedures. METHODS: The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a consensus group of clinical scientists to perform a modified Delphi process that encompassed e-mail communication, face-to-face meetings, in-group ballots and an electronic ESPEN membership Delphi round. RESULTS: Five key areas related to clinical nutrition were identified: concepts; procedures; organisation; delivery; and products. One core concept of clinical nutrition is malnutrition/undernutrition, which includes disease-related malnutrition (DRM) with (eq. cachexia) and without inflammation, and malnutrition/undernutrition without disease, e.g. hunger-related malnutrition. Over-nutrition (overweight and obesity) is another core concept. Sarcopenia and frailty were agreed to be separate conditions often associated with malnutrition. Examples of nutritional procedures identified include screening for subjects at nutritional risk followed by a complete nutritional assessment. Hospital and care facility catering are the basic organizational forms for providing nutrition. Oral nutritional supplementation is the preferred way of nutrition therapy but if inadequate then other forms of medical nutrition therapy, i.e. enteral tube feeding and parenteral (intravenous) nutrition, becomes the major way of nutrient delivery. CONCLUSION: An agreement of basic nutritional terminology to be used in clinical practice, research, and the ESPEN guideline developments has been established. This terminology consensus may help to support future global consensus efforts and updates of classification systems such as the International Classification of Disease (ICD). The continuous growth of knowledge in all areas addressed in this statement will provide the foundation for future revisions

Biogeographical Survey Identifies Consistent Alternative Physiological Optima and a Minor Role for Environmental Drivers in Maintaining a Polymorphism

The contribution of adaptive mechanisms in maintaining genetic polymorphisms is still debated in many systems. To understand the contribution of selective factors in maintaining polymorphism, we investigated large-scale (>1000 km) geographic variation in morph frequencies and fitness-related physiological traits in the damselfly Nehalennia irene. As fitness-related physiological traits, we investigated investment in immune function (phenoloxidase activity), energy storage and fecundity (abdomen protein and lipid content), and flight muscles (thorax protein content). In the first part of the study, our aim was to identify selective agents maintaining the large-scale spatial variation in morph frequencies. Morph frequencies varied considerably among populations, but, in contrast to expectation, in a geographically unstructured way. Furthermore, frequencies co-varied only weakly with the numerous investigated ecological parameters. This suggests that spatial frequency patterns are driven by stochastic processes, or alternatively, are consequence of highly variable and currently unidentified ecological conditions. In line with this, the investigated ecological parameters did not affect the fitness-related physiological traits differently in both morphs. In the second part of the study, we aimed at identifying trade-offs between fitness-related physiological traits that may contribute to the local maintenance of both colour morphs by defining alternative phenotypic optima, and test the spatial consistency of such trade-off patterns. The female morph with higher levels of phenoloxidase activity had a lower thorax protein content, and vice versa, suggesting a trade-off between investments in immune function and in flight muscles. This physiological trade-off was consistent across the geographical scale studied and supports widespread correlational selection, possibly driven by male harassment, favouring alternative trait combinations in both female morphs

An international study of the quality of life of adult patients treated with home parenteral nutrition

Background & aims: Home parenteral nutrition-quality of life (HPN-QOL©) is a self-assessment tool for the measurement of QOL in patients on HPN. The aims of this study were: to re-assess the basic psychometric properties of the HPN-QOL© in a multinational sample of adult patients; to provide a description of QOL dimensions by short and long HPN treatment duration; to explore clinical factors potentially associated to QOL scores. Methods: Patients (n = 699) from 14 countries completed the HPN-QOL©. The questionnaires were analysed to evaluate data completeness, convergent/discriminant validity and internal-consistency reliability. The association of overall QOL and HPN treatment duration as well as other clinical factors were investigated using multivariable linear regression models. Results: The analysis of the multitrait-scaling and internal consistency indicates a good fit with the questionnaire structure for most items. Item discriminant validity correlation was satisfactory and psychometric evaluation of the HPN-QOL© in the different English, French and Italian language patient sub-groups confirmed psychometric equivalence of the three questionnaire versions. The results of the multivariable linear regression showed that QOL scores were significantly associated with HPN duration (better in long-term), underlying disease (better in Crohn's disease and mesenteric ischaemia) and living status (worse in living alone) and, after adjusting for the other factors, with the number of days of HPN infusion per week. Conclusions: The HPN-QOL©, is a valid tool for measurement of QOL in patients on HPN, to be used in the clinical practice as well as in research

Second-generation colon capsule endoscopy compared with colonoscopy

Colon capsule endoscopy (CCE) represents a noninvasive technology that allows visualization of the colon without requiring sedation and air insufflation. A second-generation colon capsule endoscopy system (PillCam Colon 2) (CCE-2) was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. OBJECTIVE: To assess the feasibility, accuracy, and safety of CCE-2 in a head-to-head comparison with colonoscopy. DESIGN AND SETTING: Prospective, multicenter trial including 8 European sites. PATIENTS: This study involved 117 patients (mean age 60 years). Data from 109 patients were analyzed. INTERVENTION: CCE-2 was prospectively compared with conventional colonoscopy as the criterion standard for the detection of colorectal polyps that are >/=6 mm or masses in a cohort of patients at average or increased risk of colorectal neoplasia. Colonoscopy was independently performed within 10 hours after capsule ingestion or on the next day. MAIN OUTCOME MEASUREMENTS: CCE-2 sensitivity and specificity for detecting patients with polyps >/=6 mm and >/=10 mm were assessed. Capsule-positive but colonoscopy-negative cases were counted as false positive. Capsule excretion rate, level of bowel preparation, and rate of adverse events also were assessed. RESULTS: Per-patient CCE-2 sensitivity for polyps >/=6 mm and >/=10 mm was 84% and 88%, with specificities of 64% and 95%, respectively. All 3 invasive carcinomas were detected by CCE-2. The capsule excretion rate was 88% within 10 hours. Overall colon cleanliness for CCE-2 was adequate in 81% of patients. LIMITATIONS: Not unblinding the CCE-2 results at colonoscopy; heterogenous patient population; nonconsecutive patients. CONCLUSION: In this European, multicenter study, CCE-2 appeared to have a high sensitivity for the detection of clinically relevant polypoid lesions, and it might be considered an adequate tool for colorectal imaging