Body composition, physical activity, and quality of life in pediatric patients with inflammatory bowel disease on anti-TNF therapy-an observational follow-up study.

BACKGROUND: Poor outcome of inflammatory bowel disease (IBD) is associated with malnutrition. Our aim was to compare body composition (BC) and physical activity (PA) between patients with IBD and healthy controls, and to assess the changes in BC, PA and health related quality of life (HRQoL) in children with IBD during anti-TNF therapy. METHODS: 32 children with IBD (21 with Crohn's disease (CD), (age: 15.2 ± 2.6 years, 9 male) and 11 with ulcerative colitis (UC), (age: 16.4 ± 2.2 years, 5 male) participated in this prospective, observational follow up study conducted at Semmelweis University, Hungary. As control population, 307 children (age: 14.3 ± 2.1) (mean ± SD) were included. We assessed BC via bioelectric impedance, PA and HRQoL by questionnaires at initiation of anti-TNF therapy, and at two and six months later. The general linear model and Friedman test were applied to track changes in each variable. RESULTS: During follow-up, the fat-free mass Z score of children with CD increased significantly (-0.3 vs 0.1, p = 0.04), while the BC of patients with UC did not change. PA of CD patients was lower at baseline compared to healthy controls (1.1 vs. 2.4), but by the end of the follow up the difference disappeared. CONCLUSIONS: The fat-free mass as well as PA of CD patients increased during the first six months of anti-TNF treatment. As malnutrition and inactivity affects children with IBD during an important physical and mental developmental period, encouraging them to engage in more physical activity, and monitoring nutritional status should be an important goal in patient care.

The Use of Off-Label Medications in Newborn Infants Despite an Approved Alternative Being Available-Results of a National Survey.

Neonates continue to be treated with off-label or unlicensed drugs while in hospital. However, some medications that have previously been used in adults underwent clinical testing and licensure for use with a different indication in the neonatal and pediatric population. Almost always, the marketing of these newly approved substances in a niche indication is accompanied by a steep increase in the price of the compound. We investigated the use of the approved formulation or the cheaper off-label alternative of Ibuprofen (Pedea®), Propanolol (Hemangiol®) and Caffeine Citrate (Peyona®) in neonatal clinical practice by conducting a National Survey of 214 Perinatal Centers in Germany. We also assessed price differences between on- and off-label alternatives and the extend of the clinical development program of the on-label medication in the neonatal population. On-label medication was more frequently used than the off-label alternative in all indications (PDA: on-label to off-label ratio 1:0.26, Apnea: 1:0.56, Hemangioma 1:0.76). All sponsors did conduct placebo-controlled Phase III trials with efficacy and safety endpoints in the target population and the number of participants in the target population varied between 82 and 497. Costs for the three drugs in their approved and marketed formulations increased in median 405-fold compared with the corresponding off-label alternative. Overall, about one out of three neonatologists prescribed an off-label or non-approved drug to patients despite an alternative medication that is approved for the indication in the target population being available.

Bacterial contamination rates in extracorporeal photopheresis.

BACKGROUND: Extracorporeal photopheresis (ECP) is an immunosuppressive treatment that involves leukocyte apheresis, psoralen and UV light treatment, and subsequent reinfusion. Patients treated with ECP are usually immunosuppressed. Bacterial contamination therefore poses a much unwanted risk, but incidence data are lacking. PATIENTS AND METHODS: We screened all 1922 consecutive ECP procedures scheduled within a roughly 3-year period for eligibility. Those with missing data on ECP method (inline or offline) or type of venous access (peripheral or central) were excluded. ECPs with complete aerobic and anaerobic microbial testing of baseline patient blood samples (n = 1637) and of ECP cell concentrates (n = 1814) were included in the analysis. RESULTS: A test for microbial contamination was positive for 1.82% of the cell concentrates, with central venous access was the most significant risk factor for the contamination (odds ratio = 19). Patient blood samples were positive in 3.85% of cases, but no patients became septic. Staphylococcus spp. were most abundant, and products with bacterial contamination did not cause side effects after reinfusion. There were no significant differences in contamination rates between inline and offline ECP. CONCLUSION: These findings stress the importance of sterile procedures and the benefits of using peripheral over central venous access for reducing the risk of bacterial contamination in ECP.

Transcranial Doppler Sonography Defined Vasospasm, Ischemic Brain Lesions, and Delayed Ischemic Neurological Deficit in Younger and Elderly Patients after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Vasospasm, delayed ischemic neurologic deficit (DIND), and ischemic brain lesions after acute subarachnoid hemorrhage (SAH) are associated with increased morbidity and mortality. The purpose of this study was to analyze age cutoffs for vasospasm, DIND, and ischemic brain lesions after SAH. METHODS: This study included 292 aneurysmal SAH patients from January 2005 to December 2015. Patients' data were extracted from a prospective database with measurements of transcranial Doppler sonography. Any vasospasm was defined as a maximum mean flow velocity (MMFV) >120 cm/sec. Severe vasospasms were defined as at least 2 measurements of MMFVs >200 cm/sec or an increase of MMFV >50 cm/sec/24 hours over 2 consecutive days or a new neurologic deficit. All MMFVs >120 cm/sec in absence of severe vasospasm criteria were defined as mild vasospasm. Age-related cutoff values were calculated using receiver operating curve analysis. RESULTS: Any vasospasms occurred in 142 patients and thereof mild vasospasm in 86/142 (60.6%) patients and severe vasospasm in 56/142 patients (39.4%). Significantly higher incidences of any vasospasm (P = 0.005), severe vasospasm (P = 0.003), DIND (P = 0.031), and ischemic brain lesions (P = 0.04) were observed in patients aged <50 years. According to receiver operating curve analysis, the optimal age cutoff was 50 years for the presence of overall vasospasms, severe vasospasms, DIND, and ischemic brain lesions and 65 years for mild vasospasms. CONCLUSIONS: Higher incidences of any vasospasms, severe vasospasms, DIND, and ischemic brain lesions were observed in younger SAH patients.

Parenteral nutrition support for patients with pancreatic cancer--improvement of the nutritional status and the therapeutic outcome.

BACKGROUND: Malnutrition is a frequent and serious problem of patients with pancreatic cancer (i.e. due to exocrine pancreatic insufficiency, postoperative syndromes, anorexia, chemotherapy, and/or tumor progression). In many cases it has negative effects on the quality of life or on the tumor therapy. We investigated if malnutrition can be resolved or corrected by adequate home parenteral nutrition (PN) of pancreatic cancer (PaCa) patients, in cases where dietary advice and oral nutrition supplementation failed to correct the deficiencies. The energy supply via PN was analyzed in patients with PaCa, with focus on the single components in compounded PN. PATIENTS AND METHODS: We examined a group of six women and eleven men with assured PaCa disease at different tumor stages (mean age: 64 years). Indications for PN were a reduction of body weight of >5 % in three months and/or a long-term reduced nutritional status, reduced results of the bio-electrical impedance analysis (BIA), malassimilation and/or clinical symptoms like severe diarrhoea/vomitus, preventing adequate oral nutrition for weeks. The PN, administered via port-catheter, was initiated while the patients were undergoing chemotherapy. The course of treatment was assessed based on body weight, BIA (Data-Input Nutriguard-M), on laboratory parameters and on personal evaluation of the patients' quality of life. Retrospectively, the patients were subdivided into two groups (Gr): Gr1 (n=10) had a survival period of more than 5, up to more than 37 months, after the start of PN and Gr2 (n=7) had a survival between 1-4 months after start of PN. The calculations of the energy supply were based on the patients' body weight (per kg). Fluid volume, relation of macronutrients and addition of fish oil to PN are described in detail. RESULTS: Gr1: Eight of ten patients already showed an increase of body weight with the initial PN, two patients after dose adaption. This positive impact was also observable on the cellular level by means of BIA results (phase angle, body cell mass (BCM), extracellular mass (ECM), cell content and ECM/BCM Index). Two patients, who were receiving PN for over two or three periods, showed reproducibility of the results; while when PN was interrupted all BIA parameters degraded and they ameliorated with the restart of PN. Gr2: In these patients PN was started in the late stage of the tumor disease in order to allow for a--from the retrospective point of view--last, but ineffective chemotherapy. The data indicated that the weight loss could be retarded, even if the effects on body weight and BIA parameters were found to be less pronounced compared to Gr1. The mean energy supply of both groups, however, was similar: 8,823 kcal (Gr1) per week compared to 9,572 kcal (Gr2) per week. The majority of patients claimed to be quicker and more powerful under PN and to some extent the appetite was enhanced. CONCLUSION: A timely onset of PN with sufficient calories leads to an improved nutritional status of patients with PaCa disease. PN enhances the quality of life, the administration of tumor therapy without interruption and therefore may lead to a better success of the entire therapy. For late-stage tumor patients (Gr2) the quality of life can, at least, be improved. The success of PN is significantly dependent upon the patients' compliance, which could be achieved through intensive consulting and support of all patients and their relatives.

Stable carbon isotope composition of c9,t11-conjugated linoleic acid in cow's milk as related to dietary fatty acids.

This study explores the potential use of stable carbon isotope ratios (δ(13)C) of single fatty acids (FA) as tracers for the transformation of FA from diet to milk, with focus on the metabolic origin of c9,t11-18:2. For this purpose, dairy cows were fed diets based exclusively on C(3) and C(4) plants. The FA in milk and feed were fractionated by silver-ion thin-layer chromatography and analyzed for their δ(13)C values. Mean δ(13)C values of FA from C(3) milk were lower compared to those from C(4) milk (-30.1‰ vs. -24.9‰, respectively). In both groups the most negative δ(13)C values of all FA analyzed were measured for c9,t11-18:2 (C(3) milk = -37.0 ± 2.7‰; C(4) milk -31.4 ± 1.4‰). Compared to the dietary precursors 18:2n-6 and 18:3n-3, no significant (13)C-depletion was measured in t11-18:1. This suggests that the δ(13)C-change in c9,t11-18:2 did not originate from the microbial biohydrogenation in the rumen, but most probably from endogenous desaturation of t11-18:1. It appears that the natural δ(13)C differences in some dietary FA are at least partly preserved in milk FA. Therefore, carbon isotope analyses of individual FA could be useful for studying metabolic transformation processes in ruminants.

Dietary α-linolenic acid inhibits arterial thrombus formation, tissue factor expression, and platelet activation.

OBJECTIVE: Plant-derived α-linolenic acid (ALA) may constitute an attractive cardioprotective alternative to fish-derived n-3 fatty acids. However, the effect of dietary ALA on arterial thrombus formation remains unknown. METHODS AND RESULTS: Male C57Bl/6 mice were fed a high-ALA or low-ALA diet for 2 weeks. Arterial thrombus formation was delayed in mice fed a high-ALA diet compared with those on a low-ALA diet (n=7; P<0.005). Dietary ALA impaired platelet aggregation to collagen and thrombin (n=5; P<0.005) and decreased p38 mitogen-activated protein kinase activation in platelets. Dietary ALA impaired arterial tissue factor (TF) expression, TF activity, and nuclear factor-κB activity (n=7; P<0.05); plasma clotting times and plasma thrombin generation did not differ (n=5; P=not significant). In cultured human vascular smooth muscle and endothelial cells, ALA inhibited TF expression and activity (n=4; P<0.01). Inhibition of TF expression occurred at the transcriptional level via the mitogen-activated protein kinase p38 in smooth muscle cells and p38, extracellular signal-regulated kinases 1 and 2, and c-Jun N-terminal kinases 1 and 2 in endothelial cells. CONCLUSIONS: ALA impairs arterial thrombus formation, TF expression, and platelet activation and thereby represents an attractive nutritional intervention with direct dual antithrombotic effects.

Dietary α-linolenic acid diminishes experimental atherogenesis and restricts T cell-driven inflammation.

AIMS: Epidemiological studies report an inverse association between plant-derived dietary α-linolenic acid (ALA) and cardiovascular events. However, little is known about the mechanism of this protection. We assessed the cellular and molecular mechanisms of dietary ALA (flaxseed) on atherosclerosis in a mouse model. METHODS AND RESULTS: Eight-week-old male apolipoprotein E knockout (ApoE(-/-)) mice were fed a 0.21 % (w/w) cholesterol diet for 16 weeks containing either a high ALA [7.3 % (w/w); n = 10] or low ALA content [0.03 % (w/w); n = 10]. Bioavailability, chain elongation, and fatty acid metabolism were measured by gas chromatography of tissue lysates and urine. Plaques were assessed using immunohistochemistry. T cell proliferation was investigated in primary murine CD3-positive lymphocytes. T cell differentiation and activation was assessed by expression analyses of interferon-γ, interleukin-4, and tumour necrosis factor α (TNFα) using quantitative PCR and ELISA. Dietary ALA increased aortic tissue levels of ALA as well as of the n-3 long chain fatty acids (LC n-3 FA) eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. The high ALA diet reduced plaque area by 50% and decreased plaque T cell content as well as expression of vascular cell adhesion molecule-1 and TNFα. Both dietary ALA and direct ALA exposure restricted T cell proliferation, differentiation, and inflammatory activity. Dietary ALA shifted prostaglandin and isoprostane formation towards 3-series compounds, potentially contributing to the atheroprotective effects of ALA. CONCLUSION: Dietary ALA diminishes experimental atherogenesis and restricts T cell-driven inflammation, thus providing the proof-of-principle that plant-derived ALA may provide a valuable alternative to marine LC n-3 FA.

Characterization of rapeseed (Brassica napus) oils by bulk C, O, H, and fatty acid C stable isotope analyses.

Rapeseed ( Brassica napus ) oils differing in cultivar, sites of growth, and harvest year were characterized by fatty acid concentrations and carbon, hydrogen, and oxygen stable isotope analyses of bulk oils (delta(13)C(bulk), delta(2)H(bulk), delta(18)O(bulk) values) and individual fatty acids (delta(13)C(FA)). The delta(13)C(bulk), delta(2)H(bulk), and delta(18)O(bulk) values were determined by continuous flow combustion and high-temperature conversion elemental analyzer-isotope ratio mass spectrometry (EA/IRMS, TC-EA/IRMS). The delta(13)C(FA) values were determined using gas chromatography--combustion-isotope ratio mass spectrometry (GC/C/IRMS). For comparison, other C(3) vegetable oils rich in linolenic acid (flax and false flax oils) and rich in linoleic acid (poppy, sunflower, and safflower oils) were submitted to the same chemical and isotopic analyses. The bulk and molecular delta(13)C values were typical for C(3) plants. The delta(13)C value of palmitic acid (delta(13)C(16:0)) and n-3 alpha-linolenic acid (delta(13)C(18:3n-3)) differed (p < 0.001) between rape, flax, and poppy oils. Also within species, significant differences of delta(13)C(FA) were observed (p < 0.01). The hydrogen and oxygen isotope compositions of rape oil differed between cultivars (p < 0.05). Major differences in the individual delta(13)C(FA) values were found. A plant-specific carbon isotope fractionation occurs during the biosynthesis of the fatty acids and particularly during desaturation of C(18) acids in rape and flax. Bulk oil and specific fatty acid stable isotope analysis might be useful in tracing dietary lipids differing in their origin.