Assessment of nutritional status of patients with Crohn’s disease

Introduction: Crohn's disease (CD) is an inflammatory bowel disease, is characterized by periods of active disease and remission and has been associated with poor nutritional status, contributing to an adverse course of the disease. The aim of this doctoral thesis was to implement a thorough nutritional assessment in a sample of people with CD targeting at the evaluation of the accuracy of various predictive equations for calculating resting energy expenditure and their comparison with indirect calorimetry, the assessment of diet’s adequacy and quality compared with current recommendations, the assessment of the prevalence of nutritional risk and nutritional disorders (i.e. malnutrition, sarcopenia, overweight and obesity) and the assessment of the potential effect of the prevalent nutritional disorders on the course of the disease after a two-years follow-up. Methods: 250 people with CD of different disease activity and disease location were included, completing a thorough medical and nutritional assessment at baseline. Four different studies were carried out. Resting energy expenditure was estimated with 14 different equations with and without body composition analysis parameters and their accuracy was evaluated by comparison with the indirect calorimetry. People’s dietary intake was assessed through two 24-hour recalls and data on energy and macronutrient intake were extracted and a food frequency questionnaire from which data regarding food group consumption were extracted allowing also evaluation of adherence to the Mediterranean diet and the recent dietary recommendations for the primary prevention of cardiovascular disease. Under-reporting of energy intake based on the cut-off points of Goldberg et al. was also estimated. The prevalence of the nutritional risk with seven different nutrition screening tools was evaluated, the prevalence of malnutrition was estimated through the Subjective Global Assessment (SGA) tool, as well as through 18 different combinations of phenotypic and etiologic Global Leadership Initiative on Malnutrition (GLIM) criteria and a version combining these 18 combinations. The prevalence of sarcopenia was based on the revised EWGSOP2 diagnostic criteria, and the prevalence of overweight and obesity was based on the World Health Organization cut-off points. The effect of the presence of malnutrition (using the GLIM criteria or SGA) and the presence of overweight and obesity with the clinical course of the disease at 6, 12 and 24 months from baseline was also examined. Results: All the available predictive equations underestimated resting energy expenditure and showed low accuracy (19-42%) in estimating true energy requirements at individual and group level compared with indirect calorimetry. The assessment of dietary intake showed a high prevalence of low protein intake (25%) and a low-to-moderate diet’s quality, as reflected by a higher intake of sugars and saturated fatty acids, a higher consumption of sweets and a lower consumption of fruits, vegetables, legumes, non-refined cereals and dairy products compared to the recommended. A moderate adherence to the Mediterranean diet and dietary guidelines for the primary prevention of cardiovascular disease was observed. Although there was an improvement in dietary intake during remission, it remained far from the recommended. These results did not change after taking into account dietary under-reporting. The prevalence of nutritional risk ranged from 6-41.8%, the prevalence of malnutrition based on SGA was 22.9%, based on the combined version of GLIM criteria was 18.5% and based on 18 different GLIM combinations was 4.9-14.5%. The prevalence of sarcopenia was particularly low (2.1%) and the prevalence of overweight and obesity was high (60.8%). When examining the effect of the nutritional disorders on the course of the disease, it was observed that the presence of malnutrition based on the combined GLIM criteria was associated with an increased likelihood of intensification or change of a biologic agent and total adverse outcome at 6 months, based on the SGA was associated with an increased likelihood of active disease at 12 months and the presence of obesity was associated with an increased likelihood of active disease only at 6 months, taking into account several confounding factors. Conclusions: The results of this thesis highlighted problems when applying methodologies to assess the nutritional status of people with CD and confirmed the presence of nutritional disorders in CD that are associated with clinical outcomes underlining the need for early diagnosis and treatment, aiming to improve people’s health and disease prognosis.Εισαγωγή: Η νόσος Crohn ανήκει στις ιδιοπαθείς φλεγμονώδεις νόσους του εντέρου, χαρακτηρίζεται από περιόδους ενεργούς νόσου και υφέσεων και σχετίζεται με διαταραχές θρέψης των ατόμων, καθιστώντας μια δυσμενέστερη πορεία της νόσου. Σκοπός της παρούσας διδακτορικής διατριβής ήταν η ενδελεχής διατροφική αξιολόγηση των ατόμων με νόσο Crohn με στόχο την αξιολόγηση της ακρίβειας διαφόρων προβλεπτικών εξισώσεων υπολογισμού ενεργειακών αναγκών και τη σύγκριση αυτών με τη μέθοδο της έμμεσης θερμιδομετρίας, την αξιολόγηση της επάρκειας της διαιτητικής πρόσληψης και της ποιότητας της δίαιτας και τη σύγκριση αυτών με τις τρέχουσες κατευθυντήριες συστάσεις, την εκτίμηση του επιπολασμού διατροφικού κινδύνου και των διαταραχών θρέψης (δυσθρεψία, σαρκοπενία, υπέρβαρο και παχυσαρκία) και την εκτίμηση της επίδρασης των διαταραχών θρέψης στην πορεία της νόσου μετά από διετή παρακολούθηση. Μεθοδολογία: Εντάχθηκαν 250 άτομα με νόσο Crohn διαφορετικής ενεργότητας και ταξινόμησης νόσου που υποβλήθηκαν σε πλήρη ιατρική και διατροφική εκτίμηση κατά την εισαγωγή στο ερευνητικό πρωτόκολλο. Οι ενεργειακές ανάγκες ηρεμίας των εθελοντών υπολογίστηκαν με 14 διαφορετικές εξισώσεις, με και χωρίς παραμέτρους της σύστασης σώματος, και η αξιολόγηση της ακρίβειας αυτών πραγματοποιήθηκε με σύγκριση με τη μέθοδο της έμμεσης θερμιδομετρίας. Η διαιτητική πρόσληψη των ατόμων αξιολογήθηκε μέσω δύο ανακλήσεων 24ώρου από τις οποίες εξήχθησαν δεδομένα για την πρόσληψη ενέργειας και μακροθρεπτικών συστατικών και από ένα ερωτηματολόγιο συχνότητας κατανάλωσης τροφίμων από το οποίο εξήχθησαν δεδομένα για την κατανάλωση ομάδων τροφίμων, την προσκόλληση στη Μεσογειακή δίαιτα και στις πρόσφατες διατροφικές συστάσεις για την πρωτογενή πρόληψη καρδιαγγειακών νοσημάτων. Η εκτίμηση της υποκαταγραφής της ενεργειακής πρόσληψης βασίστηκε στις κατωφλικές τιμές των Goldberg και συν. Αξιολογήθηκε ο επιπολασμός διατροφικού κινδύνου με διαφορετικά εργαλεία ανίχνευσης και ο επιπολασμός δυσθρεψίας βάσει των κριτηρίων Global Leadership Initiative on Malnutrition (GLIM) και του εργαλείου Subjective Global Assessment (SGA), ο επιπολασμός σαρκοπενίας βάσει των αναθεωρημένων διαγνωστικών κριτηρίων σαρκοπενίας European Working Group on Sarcopenia in Older People (EWGSOP2) και ο επιπολασμός υπέρβαρου και παχυσαρκίας με βάση τις κατωφλικές τιμές του Παγκόσμιου Οργανισμού Υγείας. Επιπλέον, δημιουργήθηκαν 18 διαφορετικοί συνδυασμοί φαινοτυπικών και αιτιολογικών κριτηρίων GLIM. Τέλος, η παρουσία δυσθρεψίας (βάσει GLIM και SGA), υπέρβαρου και παχυσαρκίας συσχετίστηκε με την πορεία της νόσου Crohn στους 6, 12 και 24 μήνες από την ένταξη στη μελέτη. Αποτελέσματα: Όλες οι προβλεπτικές εξισώσεις υπολογισμού ενεργειακών αναγκών ηρεμίας υποεκτιμούσαν τον μεταβολικό ρυθμό ηρεμίας και έδειξαν χαμηλή ακρίβεια (19-42%) στην εκτίμηση των πραγματικών ενεργειακών αναγκών σε ατομικό και ομαδικό επίπεδο συγκριτικά με την έμμεση θερμιδομετρία. Η αξιολόγηση της διαιτητικής πρόσληψης έδειξε έναν υψηλό επιπολασμό χαμηλής πρωτεϊνικής πρόσληψης (25%) και προσκόλληση σε μια χαμηλής-μέτριας ποιότητας δίαιτα, με υψηλότερη πρόσληψη απλών υδατανθράκων και κορεσμένων λιπαρών οξέων, υψηλότερη κατανάλωση γλυκών και χαμηλότερη κατανάλωση φρούτων, λαχανικών, οσπρίων, μη επεξεργασμένων δημητριακών και γαλακτοκομικών προϊόντων σε σύγκριση με τη συνιστώμενη. Η προσκόλληση στη Μεσογειακή δίαιτα και στις οδηγίες για την πρόληψη της καρδιαγγειακής νόσου εκτιμήθηκε ως μέτρια. Τα άτομα σε ύφεση ανέφεραν βελτιωμένη διαιτητική πρόσληψη συγκριτικά με εκείνα με ενεργή νόσο, ωστόσο χαμηλότερη από τη συνιστώμενη. Τα αποτελέσματα αυτά δεν διαφοροποιήθηκαν όταν εξετάστηκε η επάρκεια καταγραφής της διαιτητικής πρόσληψης. Ο επιπολασμός διατροφικού κινδύνου ήταν 6-41,8% αναλόγως εργαλείου, ο επιπολασμός δυσθρεψίας βάσει SGA ήταν 22,9%, βάσει συνδυαστικής εκδοχής GLIM 18,5%, και βάσει των 18 εκδοχών GLIM 4,9-14,5%, ο επιπολασμός σαρκοπενίας ήταν ιδιαίτερα χαμηλός (2,1%) και ο επιπολασμός υπέρβαρου/παχυσαρκίας υψηλός (60,8%). Παρατηρήθηκε ότι η παρουσία δυσθρεψίας βάσει GLIM συσχετίστηκε με αυξημένη πιθανότητα εντατικοποίησης ή αλλαγής βιολογικού παράγοντα και δυσμενούς έκβασης στους 6 μήνες, βάσει SGA συσχετίστηκε με αυξημένη πιθανότητα παρουσίας ενεργούς νόσου στους 12 μήνες και η παρουσία παχυσαρκίας συσχετίστηκε με αυξημένη πιθανότητα ενεργούς νόσου μόνο στους 6 μήνες λαμβάνοντας υπόψη διάφορους συγχυτικούς παράγοντες. Συμπεράσματα: Τα αποτελέσματα της παρούσας διατριβής ανέδειξαν προβλήματα κατά την εφαρμογή μεθοδολογιών για την αξιολόγηση της διατροφικής κατάστασης ατόμων με νόσο Crohn και επιβεβαίωσαν την παρουσία διαταραχών θρέψης στη νόσο Crohn που συσχετίζονται με κλινικές εκβάσεις της νόσου και υπογραμμίζουν την ανάγκη έγκαιρης διάγνωσης και αντιμετώπισης, με στόχο τη βελτίωση της υγείας των ασθενών και της πρόγνωσης της νόσου

Peptide-Based Vaccines for Neurodegenerative Diseases: Recent Endeavors and Future Perspectives

The development of peptide-based vaccines for treating human neurodegenerative diseases has been the eventual aim of many research endeavors, although no active immunotherapies have been approved for clinical use till now. A typical example of such endeavors is the effort to develop vaccines for Alzheimer’s disease based on the beta-amyloid peptide, which continues to be intensively investigated despite previous setbacks. In this paper, recent developments in peptide-based vaccines which target beta-amyloid as well as tau protein and α-synuclein are presented. Particular focus has been directed toward peptide epitopes and formulation systems selected/developed and employed to enhance vaccine efficacy and safety. Results from both, human clinical trials and animal preclinical studies conducted mainly in transgenic mice have been included. Future perspectives on the topic are also briefly discussed

A cohort of children with type 1 diabetes in Greece: predictors of direct costs of care

AimTo examine the predictors of direct costs of pediatric type 1 diabetes (T1D) in a hospital-based outpatient clinic in Greece. MethodsThe outpatient records of 89 children and adolescents (mean age: 12.055.15y) with T1D followed in the Second Department of Pediatrics, University of Athens Medical School, were analyzed. ResultsThe mean +/- SD diabetes duration was 4.9 +/- 3.88y (range: 0.25-17) and glycated hemoglobin (HbA1c) was 8.2 +/- 1.09% (66 +/- 11.9mmol/mol). A total of 80% of patients were on multiple daily injections regimen, 10% on pump therapy, and 10% on conventional regimen. Total direct costs per patient-year (ppy) were estimated at Euro2.712 [95% confidence interval (CI): 2.468-2.956]. Supply costs accounted for 73.7% of total costs and were the highest for pump therapy (P<.001). Multivariate linear regression analysis showed that costs were significantly higher for children (1) on multiple daily injections or pump therapy (r=0.364, P<.001), (2) of older age (r=0.25, P<.001) and (3) higher daily insulin dose (r=0.46, P<.001). Patients on pump therapy had significantly higher costs Euro5.538 (95%CI 4480-6597) compared with patients on multiple daily injections Euro2.447 (95% CI 2320-2574) and conventional regimen Euro1.978.5 (95%CI 1682-2275) (P=.0001). Patients on pump therapy had better glycemic control compared with all other patients [HbA1c (mean +/- SD): 7.2%+/- 1.0 vs 8.3% +/- 1.5, P=.039]. Conclusion The total T1D cost in this cohort of Greek children was Euro2712 ppy. The main factor that predicted direct cost was the use of pump. However, pump therapy was associated with better glycaemic control, which may decrease the risk of total long-term diabetes care cost

Radiochemical and radiobiological evaluation of a new Tc-99m-labelled litorin derivative

WOS: 00028107510011

Assessment of Dietary Adequacy and Quality in a Sample of Patients with Crohn’s Disease

Both under-and over-nutrition are prevalent in patients with Crohn’s Disease (CD). The aim of the present study was to evaluate dietary intake and compare it with relevant recommendations during active disease and remission, also taking into consideration the adequacy of energy reporting. Dietary quality was assessed through adherence to the Mediterranean diet and to the European dietary guidelines for cardiovascular disease prevention (CVD-score). Malnutrition was diagnosed with the GLIM criteria. There were 237 patients evaluated (54.9% males, 41.3 ± 14.1 years and 37.6% with active disease). In the total sample, high prevalence of overweight/obesity (61.6%) and low prevalence of malnutrition (11.4%) were observed, whereas 25.5% reported low protein intake in the sub-sample of adequate energy reporters. The mean MedDietScore was 28.0 ± 5.5 and the mean CVD-score was 5.25 ± 1.36, both reflecting moderate dietary quality. Patients with active disease reported higher prevalence of low protein intake, lower carbohydrate, fibers, fruits, vegetables, legumes, and sweets consumption and a lower MedDietScore compared to patients in remission. Consumption of fibers, fruits, vegetables, and legumes while in remission did not result in reaching the recommended intakes, and dietary quality was low as reflected by the MedDietScore. In conclusion, both protein undernutrition and energy overconsumption were prevalent in the current sample and overall patients adhered to a moderate quality diet irrespective of disease stage

Perinatal, sociodemographic and lifestyle correlates of increased total and visceral fat mass levels in schoolchildren in Greece: the Healthy Growth Study

Objective: To identify possibly independent associations of perinatal, sociodemographic and lifestyle factors with childhood total and visceral body fat. Design: A representative sample of 2655 schoolchildren (9-13 years) participated in the Healthy Growth Study, a cross-sectional epidemiological study. Setting: Seventy-seven primary schools in four large regions in Greece. Subjects: A sample of 1228 children having full data on total and visceral fat mass levels, as well as on anthropometric, dietary, physical activity, physical examination, socio-economic and perinatal indices, was examined. Results: Maternal (OR= 3.03 and 1.77) and paternal obesity (OR= 1.62 and 1.78), maternal smoking during pregnancy (OR = 1.72 and 1.93) and rapid infant weight gain (OR= 1.42 and 1.96) were significantly and positively associated with children's increased total and visceral fat mass levels, respectively. Children's television watching for > 2 h/d (OR= 1.40) and maternal pre-pregnancy obesity (OR= 2.46) were associated with children's increased total and visceral fat mass level, respectively. Furthermore, increased children's physical activity (OR= 0.66 and 0.47) were significantly and negatively associated with children's total and visceral fat mass levels, respectively. Lastly, both father's age > 46 years (OR= 0.57) and higher maternal educational level (OR= 0.45) were associated with children's increased total visceral fat mass level. Conclusions: Parental sociodemographic characteristics, perinatal indices and pre-adolescent lifestyle behaviours were associated with children's abnormal levels of total and visceral fat mass. Any future programme for childhood prevention either from the perinatal age or at late childhood should take these indices into consideration