Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose.

BACKGROUND: Despite treatment with pancreatic enzyme replacement therapy (PERT), patients with cystic fibrosis (CF) can still suffer from fat malabsorption. A cause could be low intestinal pH disabling PERT. The aim of this study was to assess the association between faecal pH (as intestinal pH surrogate) and coefficient of fat absorption (CFA). Additionally, faecal free fatty acids (FFAs) were quantified to determine the amount of digested, but unabsorbed fat. METHODS: In a 24-h pilot study, CF patients followed a standardised diet with fixed PERT doses, corresponding to theoretical optimal doses determined by an in vitro digestion model. Study variables were faecal pH, fat and FFA excretion, CFA and transit time. Linear mixed regression models were applied to explore associations. RESULTS: In 43 patients, median (1st, 3rd quartile) faecal pH and CFA were 6.1% (5.8, 6.4) and 90% (84, 94), and they were positively associated (p < 0.001). An inverse relationship was found between faecal pH and total fat excretion (p < 0.01), as well as total FFA (p = 0.048). Higher faecal pH was associated with longer intestinal transit time (p = 0.049) and the use of proton pump inhibitors (p = 0.009). CONCLUSIONS: Although the clinical significance of faecal pH is not fully defined, its usefulness as a surrogate biomarker for intestinal pH should be further explored. IMPACT: Faecal pH is a physiological parameter that may be related to intestinal pH and may provide important physiopathological information on CF-related pancreatic insufficiency. Faecal pH is correlated with fat absorption, and this may explain why pancreatic enzyme replacement therapy is not effective in all patients with malabsorption related to CF. Use of proton pump inhibitors is associated to higher values of faecal pH. Faecal pH could be used as a surrogate biomarker to routinely monitor the efficacy of pancreatic enzyme replacement therapy in clinical practice. Strategies to increase intestinal pH in children with cystic fibrosis should be targeted.

Nomograms for morbidity and mortality after oncologic colon resection in the enhanced recovery era: results from a multicentric prospective national study.

PURPOSE: Predicting postoperative complications and mortality is important to plan the surgical strategy. Different scores have been proposed before to predict them but none of them have been yet implemented into the routine clinical practice because their difficulties and low accuracy with new surgical strategies and enhanced recovery. The main aim of this study is to identify risk factors for postoperative morbidity and mortality after colonic resection (CR) without protective stomas, in order to develop a comprehensive, up-to-date, simple, reliable, and applicable model for the preoperative assessment of patients with colon cancer. METHODS: Multivariable analysis was performed to identify risk factors for 60-day morbidity and mortality. Coefficients derived from the regression model were used in the nomograms to predict morbidity and mortality. RESULTS: Three thousand one hundred ninety-three patients from 52 hospitals were included into the analysis. Sixty-day postoperative complications rate was 28.3% and the mortality rate was 3%. In multivariable analysis the independent risk factors for postoperative complications were age, male gender, liver and pulmonary diseases, obesity, preoperative albumin, anticoagulant treatment, open surgery, intraoperative complications, and urgent surgery. Independent risk factors for mortality were age, preoperative albumin anticoagulant treatment, and intraoperative complications. CONCLUSIONS: Risk factors for morbidity and mortality after CR for cancer were identified and two easy predictive tools were developed. Both of them could provide important information for preoperative consultation and surgical planning in the time of enhance recovery.

Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients.

microRNAs (miRNAs) are small RNAs that regulate different biological processes. Our objective was to identify miRNAs dysregulated in plasma and tissue of patients with abdominal aortic aneurysm (AAA) and explore new potential targets involved in AAA. Fifty-seven subjects were recruited for a plasma study (30 AAA patients, 16 healthy volunteers and 11 patients with atherosclerosis). The expression level of 179 miRNAs was screened in plasma from a subset of samples, and dysregulated miRNAs were validated in the entire study population. Dysregulated miRNAs were also quantified in aortic tissue of 21 AAA patients and 8 organ donors. Applying a gene set enrichment analysis, an interaction map of dysregulated miRNAs and their targets was built, and selected targets were quantified in tissue samples. miR-27b-3p and miR-221-3p were overexpressed in plasma of AAA patients compared with healthy controls, 1.6 times and 1.9 times, respectively. In AAA tissue, six miRNAs (miR-1, miR-27b-3p, miR-29b-3p, miR-133a-3p, miR-133b, and miR-195-5p) were underexpressed from 1.6 to 4.8 times and four miRNAs (miR-146a-5p, miR-21-5p, miR-144-3p, and miR-103a-3p) were overexpressed from 1.3 to 7.2 times. Thrombospondin-2, a target of miR-195-5p, was increased in AAA tissue and negatively correlated with the expression of miR-195-5p, suggesting their involvement in a common regulatory mechanism.

The width of the third ventricle associates with cognition and behaviour in motor neuron disease.

OBJECTIVES: An enlarged width of the third ventricle (WTV) has been described in amyotrophic lateral sclerosis (ALS) patients, although its clinical meaning is unknown. The aims of this study were to evaluate the contribution of demographical, clinical and genetic factors to the WTV in different motor neuron disease (MND) phenotypes and to assess its brain structural correlates. MATERIALS AND METHODS: The WTV was measured by transcranial ultrasound in 107 MND patients (82 diagnosed with classical ALS, 16 with progressive muscular atrophy and 9 with primary lateral sclerosis) and 25 controls. Genetic analysis, and neurological and neuropsychological examinations were performed in patients. Brain volumetric analysis of MR images was obtained in 85 patients. The association of WTV with demographical, clinical, genetic and neuropsychological variables as well as with brain volumes was assessed by multivariable models. RESULTS: Eighteen patients were diagnosed with genetic MND and 42.3% of patients showed executive or behavioural impairment (EBI). MND patients showed larger WTV than controls. The WTV was significantly associated with age, spinal onset and the presence of EBI, but not with the genetic background, the phenotype or disability. Greater WTV was also associated with reduced subcortical grey matter volume, but not with the cortical or the white matter volume. CONCLUSIONS: The enlargement of the WTV found in the different MND phenotypes is attributable to the subcortical grey matter atrophy and is associated with cognitive and behavioural impairment. Larger longitudinal studies are needed to determine its role as biomarker in MND patients with frontotemporal dementia.

Detection and quantification of gluten immunogenic peptides in feces of infants and their relationship with diet.

BACKGROUND: there are no effective methods to easily control the correct adherence to a gluten-free diet (GFD) in celiac disease (CD) patients. AIM: to assess the sensitivity and specificity of a rapid immunochromatographic (IC) test that detects gluten immunogenic peptides (GIP) in feces, compared to an enzyme-linked immunosorbent assay (ELISA) method. METHODS: fecal samples from healthy infants were analyzed by a rapid IC test and ELISA, both methods are based on the anti-gliadin 33-mer monoclonal antibody. Group 1 included infants aged from 6 to 24 months, with an unrestricted consumption of gluten containing cereals. Group 2 (negative controls) was comprised of infants aged from 0 to 6 months, either breastfed or formula fed who had never ingested gluten. RESULTS: in group 1 (n = 34), all infants had positive values by ELISA, the mean was 13.13 µgGIP/g (range 0.56-46.79). The IC test was negative in 5/20 cases and there was a significant correlation (p=0.006) between the mean daily gluten intake and GIP in feces. In group 2 (n = 20), all the samples were negative by both methods. Moreover, the Kappa Fleiss concordance index (Kappa = 0.79 CI95% [0.616, 0.965]) indicated a moderate concordance between both methods. CONCLUSIONS: according to our results, both methods are highly specific. However, the ELISA test had a higher sensitivity. Although we found a significant correlation between the amount of gluten consumed and GIP recovery in feces, further studies are needed to clarify the impact of individual confounding factors in GIP recovery.

Cytomegalovirus reactivation in liver transplant recipients due to hepatitis C cirrhosis is associated with higher cardiovascular risk - an observational, retrospective study.

The association between cytomegalovirus (CMV) reactivation and cardiovascular risk has been reported in solid organ transplant populations; however, it has yet to be assessed in liver transplantation (LT). We aim to evaluate whether CMV reactivation is associated with cardiovascular events (CVE) in HCV-LT patients. LT patients (2010 and 2014) due to HCV cirrhosis were included. Clinically significant CMV (CS-CMV) was defined as viral load (VL) >5000 copies/ml, need of therapy or CMV disease. Baseline variables and endpoint measures (CVE, survival, severe recurrent hepatitis C, de novo tumors, and diabetes) were collected. One hundred and forty patients were included. At LT, a history of AHT was present in 23%, diabetes 22%, tobacco use 45%, obesity 20%, and renal impairment (eGFR < 60 ml/min) in 26.5%. CS-CMV reactivation occurred in 25% of patients. Twenty-six patients (18.5%) developed a CVE. Cox regression analysis revealed two factors significantly associated with CVE: Pre-LT DM [HR = 4.6 95% CI (1.6, 13), P = 0.004] and CS-CMV [HR = 4.7 95% CI (1.8, 12.5), P = 0.002]. CS-CMV was not independently associated with the remaining endpoints except for survival (P = 0.03). In our series, CS-CMV reactivation was associated with a greater risk of developing CVE, thus confirming data from other solid organ transplant populations and emphasizing the need for adequate CMV control.

Permanent seed implant brachytherapy in low-risk prostate cancer: Preoperative planning with 145 Gy versus real-time intraoperative planning with 160 Gy.

AIM: The present retrospective study was to compare toxicity and survival outcomes in a group of low-risk PCa patients treated with either the preoperative planning technique (145 Gy) or the real-time IoP technique (160 Gy). BACKGROUND: The two most common permanent seed implantation techniques are preoperative planning (PP) with 145 Gy and real-time intraoperative planning (IoP) with 160 Gy. Although IoP has largely replaced PP at many centres in recent years, few studies have directly compared these two techniques. MATERIALS AND METHODS: Retrospective study of 408 patients with low-risk PCa treated with permanent seed implant brachytherapy at our institution between October 2003 and December 2014. Of these, 187 patients were treated with PP at a dose of 145 Gy while 221 received real-time IoP with 160 Gy. RESULTS: At a median follow up of 90 months, 5- and 8-year rates of biochemical relapse-free survival (BRFS) were 94.8% and 86% with the IoP technique versus 90.8% and 83.9%, respectively, with PP. The maximum dose to the urethra was <217 Gy with both techniques. Despite the higher dose, IoP did not cause any significant increase in toxicity (p = 0.11). CONCLUSIONS: The present study shows that real-time intraoperative brachytherapy at a dose of 160 Gy yield better biochemical control than preoperative planning at 145 Gy. In addition, urinary toxicity did not increase, despite the dose escalation, probably because the dose constraints to the urethra were met despite the increased dose escalation. These findings support the use of real-time IoP.

Exploring the efficacy of dialectical behaviour therapy and methylphenidate on emotional comorbid symptoms in adults with attention Deficit/Hyperactivity disorder: Results of the COMPAS multicentre randomised controlled trial.

This study evaluated the efficacy of dialectical behaviour group therapy (GPT) vs. individual clinical management (CM) and methylphenidate (MPH) vs. placebo (PLB) on emotional symptoms in adults with ADHD. This longitudinal multicentre RCT compared four groups (GPT+MPH, GPT+PLB, CM+MPH, and CM+PLB) over five assessment periods, from baseline to week 130. Emotional symptomatology was assessed using SCL-90-R subscales. Of the 433 randomised participants, 371 remained for final analysis. At week 13, the GPT+MPH group showed smaller reductions in anxiety symptoms than the CM groups, but the differences disappeared at subsequent assessments. Improvements in emotional symptom were significantly predicted by reductions in core ADHD symptoms in all groups except the GPT+MPH group. The unexpected lack of between-group differences may be explained by a "floor effect", different intervention settings (group vs. individual), and psychotherapy type. Multiple regression analyses suggest a more specific effect of combined interventions (GPT+MPH). Implications for clinical practice are discussed. Clinical trial registration: ISRCTN54096201 (Current Controlled Trials).

Influential factors on dose by ionic dialysance in daily practice in chronic hemodialysis.

BACKGROUND: The determination of Kt/V by ionic dialysance is a technique that has extended its use in hemodialysis clinics. The clinical guidelines have reflected the need to validate this method as a determinant of the dose of dialysis. OBJECTIVES: Determine in daily practice, the influence of hemodialysis characteristics and medication on Kt/V results by ionic dialysance (Kt/V OCM) and compare them with Kt/V measures by serum urea (Kt/V Daugirdas). DESIGN: Cross-sectional and observational study. PARTICIPANTS: 127 patients on chronic hemodialysis. MEASUREMENTS: Descriptive variables, study variables (Kt/VOCM, Kt/VDaugidas), and the variables that modified the effect (patient temperature, serum sodium, vascular access, recirculation, blood flow, hemodialysis technique, dialyzer, acid concentrate, conductivity, dialyzate flow). RESULTS: The mean of Kt/V Daugirdas was 1.84 and the Kt/VOCM mean 1.65; Pearson's was CC r=0.54; P<0.001 and Lin CCC=0.48. In the linear regression, the variables related to hemodialysis technique showed no statistical association with the measurement obtained by Kt/VOCM. Monosodium phosphate and 20% sodium chloride dispensing were associated with a higher Kt/VOCM. CONCLUSIONS: The different technical aspects noted during HD sessions do not influence Kt/V OCM outcomes. Kt/V determined by ionic dialysance isn't similar to that determined by serum urea. When assessing dialysis doses measured by dialysance, consider that it is not the same as determined with serum urea, but it provides an approximation to estimate dialysis doses in real time. It is necessary to consider if drugs or supplements have been administered that can modify it when interpreting the results.

Cohort study with patients older than 80 years with stage 5 chronic kidney failure on hemodialysis vs conservative treatment: Survival outcomes and use of healthcare resources.

Renal replacement treatment has not been generalized to the elderly for different reasons. The main objective of the present cohort study is to compare survival in patients older than 80 years with chronic kidney disease stage 5 on renal replacement treatment with those on conservative treatment. The use of healthcare resources is compared too. A Cox proportional hazards regression analysis was run with the outcome variable death during the follow-up period. The independent variables were treatment type, age, gender, smoking habit, serum albumin, hemoglobin, Charlson Index, diabetes mellitus, arterial hypertension, ischemic cardiopathy, and neoplasm. For outcome variable "death," renal replacement treatment obtained a hazard ratio of 0.273 (P .006, CI95% 0.108-0.686) vs conservative treatment. In conclusion, patients older than 80 years with chronic kidney disease stage 5 on renal replacement treatment presented a lower mortality risk than those receiving conservative treatment. Comorbidity and age are both associated with mortality, but do not cancel out the survival advantage. In healthcare resources, the renal replacement treatment group made greater use of tests, medical visits and consumption of hospital dispensing drugs, but there were no differences with respect to the days of hospital admission or assistance in home hospitalization.

Publisher Correction: Clinical Features of Neuroblastoma With 11q Deletion: An Increase in Relapse Probabilities In Localized And 4S Stages.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

In vitro digestion models to assess lipolysis: The impact of the simulated conditions of gastric and intestinal pH, bile salts and digestive fluids.

In vitro digestion models are a valid methodology to study nutrient hydrolysis by simulating standard physiological gastrointestinal conditions. However, there are pathologies in which some conditions are affected, which should be considered in the design of an in vitro digestion study. Our work aims at elucidating the role of different gastrointestinal conditions on lipolysis. In the context of exocrine pancreatic insufficiency, gastric pH, intestinal pH, bile salts composition, bile salts concentration, fat concentration in the digestion medium and volumetric ratio digestion fluid/food were the selected study parameters. The pH-stat method was applied to assess lipolysis extent and kinetics. Descriptive results were summarised in digestibility curves and beta regression models were used to explain the effect (odds ratio, OR) of the studied conditions on lipolysis. Additionally, distribution of emulsion droplets was measured and optical microscopy images of fat globules were taken in a selection of experimental conditions. Results showed that intestinal pH was the variable with the highest effect on lipolysis (OR 22.86, p < 0.001), followed by fat concentration in the digestion medium (OR 6.76, p < 0.001) and bile salts concentration (OR 1.56, p < 0.001). Overall, lipolysis was significantly associated with particle size (OR - 6.98, p < 0.001). We conclude that the assessment of lipolysis by means of in vitro digestion models is sensitive to the simulated gastrointestinal conditions, which should be adapted to the real physiological conditions occurring in altered health conditions.

Accuracy of the fetal cerebroplacental ratio for the detection of intrapartum compromise in nonsmall fetuses.

Objective: To study the accuracy of the cerebroplacental ratio (CPR) for the detection of intrapartum fetal compromise (IFC) in fetuses growing over the 10th centile. Methods: This was a prospective study of 569 nonsmall fetuses attending the day hospital unit of a tertiary hospital that underwent an ultrasound examination at 36-40 weeks, and were delivered within 4 weeks of examination. IFC was defined as a composite of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20 requiring cesarean section, neonatal umbilical cord pH <7.20, 5 min Apgar score <7 and postpartum admission to neonatal or pediatric intensive care units. The accuracy of CPR for the prediction of IFC was calculated alone and in combination with other perinatal parameters using univariate and multivariate logistic regression models, which alternatively included the onset of labor to evaluate the influence of induction of labor (IOL) on IFC, and a brief composite adverse outcome of two parameters to prove the strength of the approach. Results: The incidence of IFC was 17.9%. CPR sensitivity was 30.4% for a false positive rate (FFR) of 10 and 14.7% for an FPP of 5% (AUC = 0.62, p < .001). The multivariate analysis showed that only fetal gender and parity increased the predictive accuracy of CPR alone, although the improvement was poor (AUC = 0.67, p < .001). No differences were observed using any of the alternative models. Finally, IOL had no influence on IFC. Conclusions: Despite their apparent normality, a proportion of fetuses growing over the 10th centile suffer IFC. Some of them are suitable for detection by means of CPR.

A first approach for an evidence-based in vitro digestion method to adjust pancreatic enzyme replacement therapy in cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis have to take enzymatic supplements to allow for food digestion. However, an evidence-based method to adjust Pancreatic Enzyme Replacement Therapy (PERT) is inexistent, and lipid content of meals is used as a rough criterion. OBJECTIVE: In this study, an in vitro digestion model was set up to determine the theoretical optimal dose (TOD) of enzymatic supplement for a selection of foods, which is the dose that allows for maximum lipolysis extent. METHODS: A static in vitro digestion model was applied to simulate digestion of eight foods covering a wide range of lipid contents. First, the dose of the enzymatic supplement was fixed at 2000 lipase units per gram of fat (LU/g fat) using intestinal pH and bile salt concentration as variables. Second, intestinal pH and bile salt concentrations were fixed and the variable was the dose of the enzymatic supplement. Lipolysis extent was determined by measuring the free fatty acids released from initial triglycerides content of foods after digestion. Results in terms of percentage of lipolysis extent were fitted into a linear-mixed segmented model and the deducted equations were used to predict the TOD to reach 90% of lipolysis in every food. In addition, the effect of intestinal pH and bile salt concentration were investigated. RESULTS: The predictive equations obtained for the assessed foods showed that lipolysis was not only dependent on the dose of the enzyme supplement or the lipid content. Moreover, intestinal pH and bile salt concentration had significant effects on lipolysis. Therefore an evidence-based model can be developed taking into account these variables. CONCLUSIONS: Depending on food characteristics, a specific TOD should be assigned to achieve an optimal digestion extent. This work represents a first step towards an evidence-based method for PERT dosing, which will be applied in an in vivo setting to validate its efficacy.

Differences in the macronutrient and dietary fibre profile of gluten-free products as compared to their gluten-containing counterparts.

BACKGROUND/OBJECTIVES: Gluten-free diet is the lifelong therapy for patients with coeliac disease. A wide range of gluten-free products (GFP) is available, which mimics the characteristics of their gluten-containing counterparts (GCC). The aim of this study was to compare the macronutrient and dietary fibre composition of GFP and GCC currently available in Spain. SUBJECTS/METHODS: A cross-sectional study analysing the nutritional differences between 621 GFP and 600 GCC based on labelling information was conducted. Food items were categorized in one of 14 food groups. The first six ingredients were noted for each food item. A linear regression model was used to explain differences in nutritional composition between GFP and GCC and three independent models were created for bread, pasta and biscuits. RESULTS: Results showed that GCC had higher protein content than GFP, especially in flour, bread, pasta and pizza. Bread had higher total and saturated fat contents in the GFP in which palm oil was the main fat used. Flours and starchy ingredients used in GFP formulation were mainly rice and corn flours and corn starch, and palm oil was the most commonly used fat. CONCLUSIONS: In conclusion, GFP cannot currently be considered as equivalent substitutes for their GCC. The reformulation of the GFP with more healthy ingredients and ingredients is encouraged, using a healthy oil, pseudocereals and whole flour.

Clinical Features of Neuroblastoma With 11q Deletion: An Increase in Relapse Probabilities In Localized And 4S Stages.

Neuroblastoma (NB) is a heterogeneous tumor with an extremely diverse prognosis according to clinical and genetic factors, such as the presence of an 11q deletion (11q-del). A multicentric study using data from a national neuroblastic tumor database was conducted. This study compared the most important features of NB patients: presence of 11q-del, presence of MYCN amplification (MNA) and remaining cases. A total of 357 patients were followed throughout an 8-year period. 11q-del was found in sixty cases (17%). 11q-del tumors were diagnosed at an older age (median 3.29 years). Overall survival (OS) was lower in 11q-del patients (60% at 5 years), compared to all other cases (76% at 5 years) p = 0.014. Event free survival (EFS) was 35% after 5 years, which is a low number when compared with the remaining cases: 75% after 5 years (p < 0.001). Localized tumors with 11q-del have a higher risk of relapse (HR = 3.312) such as 4 s 11q-del patients (HR 7.581). 11q-del in NB is a dismal prognostic factor. Its presence predicts a bad outcome and increases relapse probability, specially in localized stages and 4 s stages. The presence of 11q aberration should be taken into consideration when stratifying neuroblastoma risk groups.

Assessing gastro-intestinal related quality of life in cystic fibrosis: Validation of PedsQL GI in children and their parents.

BACKGROUND: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency, leading to fat malabsorption, malnutrition and abdominal discomfort. Until recently, no specific tool was available for assessing gastro-intestinal related quality of life (GI QOL) in patients with CF. As the Horizon2020 project MyCyFAPP aims to improve GI QOL by using a newly designed mobile application, a sensitive and reliable outcome measure was needed. We aimed to study the applicability of the existing child-specific Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Scales and Module (PedsQL GI) in children with CF. METHODS: A multicenter, prospective observational study was performed in 6 European centers to validate the PedsQL GI in children with CF during 3 months. RESULTS: In total, 248 children and their parents were included. Within-patient variability of PedsQL GI was low (24.11), and there was reasonable agreement between children and parents (ICC 0.681). Nine of 14 subscales were informative (no ceiling effect). The PedsQL GI and the median scores for 4 subscales were significantly lower in patients compared to healthy controls. Positive associations were found between PedsQL GI and age (OR = 1.044, p = 0.004) and between PedsQL GI and BMI z-score (OR = 1.127, p = 0.036). PedsQL GI correlated with most CFQ-R subscales (r 0.268 to 0.623) and with a Visual Analogue Scale (r = 0.20). CONCLUSIONS: PedsQL GI is a valid and applicable instrument to assess GI QOL in children with CF. Future research efforts should examine the responsiveness of the CF PedsQL GI to change in the context of clinical interventions and trials.

Clinical validation of an evidence-based method to adjust Pancreatic Enzyme Replacement Therapy through a prospective interventional study in paediatric patients with Cystic Fibrosis.

BACKGROUND: A method to adjust Pancreatic Enzyme Replacement Therapy in Cystic Fibrosis is not currently available. OBJECTIVES: To assess the in vivo efficacy of a method to adjust the dose of enzymatic supplement in CF extrapolated from previous in vitro digestion studies (theoretical optimal dose, TOD). Secondly, to assess how individual patient characteristics influence the expected coefficient of fat absorption (CFA) and thus to identify an individual correction factor to improve TOD. METHODS: A prospective interventional study in 43 paediatric patients with CF from 5 European centres. They followed a 24h fixed diet with the theoretical optimal dose for each meal. Faecal collection was carried out between colorimetric markers in order to include all the faeces corresponding to the fixed diet. Beta regression models were applied to assess the associations of individual patient characteristics with the CFA. RESULTS: Median CFA was 90% (84, 94% 1st, 3rd Q.) with no significant differences among centres. Intestinal transit time was positively associated with CFA (p = 0.007), but no statistical associations were found with and age, gender, phenotype or BMI. Regression model showed no improvement of the in vitro predicted theoretical optimal dose when taking individual patient characteristics into account. CONCLUSION: Strict adherence to the theoretical optimal dose of enzymatic supplement for a prescribed meal, led to median CFA levels at the clinical target of 90% with a low variability between patients. The proposed method can be considered as a first approach for an evidence-based method in PERT dosing based on food characteristics. Results have to be confirmed in free dietary settings.

The Relative Contribution of Food Groups to Macronutrient Intake in Children with Cystic Fibrosis: A European Multicenter Assessment.

BACKGROUND: Optimal nutrition for children with cystic fibrosis (CF) improves prognosis and survival, but an increased caloric intake recommendation for this population raises concerns about the nutrient profile of their diets. OBJECTIVE: Our aim was to assess the relative contribution of food groups to the total macronutrient intake of European pediatric patients with CF. DESIGN: We conducted a cross-sectional study in which the participants recorded dietary intake from 2016 to 2017. Specifically developed nutritional composition databases were used to obtain nutritional data, including macronutrients and food groups, according to previously standardized criteria. PARTICIPANTS/SETTING: Two hundred and seven pediatric patients with CF from six European centers were involved in the My App for Cystic Fibrosis self-management project. MAIN OUTCOME MEASURES: Participants reported dietary intake with a detailed 4-day food record. STATISTICAL ANALYSIS PERFORMED: Descriptive analyses of nutrient intake, food group consumption, and dietary origin of macronutrients were conducted with R software. RESULTS: Similar patterns were found in nutrient and food group intake; both sugar and saturated fatty acids contributed >10% each to the total daily energy intake in all the centers. Large mean and median percent differences were observed in the intake of other nutrient and food groups, because sweets and snacks were consumed once or twice a day, and fruit and vegetables were consumed two or three times a day. Milk, meat, sweets and snacks, and oils were the main sources of fat in all centers. CONCLUSIONS: Study findings indicated less than optimal nutrient profiles, especially for sugars and saturated fatty acids, resulting from the high consumption of meat, dairy, and processed products and low consumption of fish, nuts, and legumes. These results can serve as a basis for future tailored interventions that target improved adherence to nutritional recommendations for patients with CF.

In Vitro Digestion of Lipids in Real Foods: Influence of Lipid Organization Within the Food Matrix and Interactions with Nonlipid Components.

In vitro digestion research has scarcely addressed the assessment of the complexity of digestion in real food. The aim of the present study was to evaluate the influence of intestinal conditions, nonlipid components, and lipid organization within the food matrix on lipolysis extent. A selection of 52 foods was studied under different simulated intestinal conditions, including those related to patients with cystic fibrosis (pH6, bile salts 1 mM due to decreased pancreatic and biliary secretions) and to healthy subjects (pH7, bile salts 10 mM). Linear mixed regression models were applied to explain associations of food properties with lipolysis. Normal intestinal conditions allowed for optimal lipolysis in most of the foods in contrast to the altered intestinal scenario (30 compared with 1 food reaching > 90% lipolysis). Lipid-protein and lipid-starch interactions were evidenced to significantly affect lipolysis (P < 0.001) in all the digestion conditions, decreasing in those foods with low fat and high protein or high starch content. In addition, under decreased intestinal pH and bile concentration, lipolysis was lower in foods with complex solid structures and continuous lipid phase than in the oil-in-water continuous aqueous phase (global P < 0.01). However, in the normal conditions lipid organization within the food matrix did not show a significant effect on lipolysis (global P = 0.08). In conclusion, food properties play a crucial role in lipolysis, which should be considered when establishing dietary recommendations. PRACTICAL APPLICATION: Food composition, lipid organization within the food matrix, and gastrointestinal conditions are key factors affecting lipolysis. Knowledge on that can be used to modulate lipolysis performance after food ingestion. Different applications are foreseen, as food design and nutritional recommendations for the general populations and specific target groups. The most immediate application is related to the scope of the research project that frames this work (www.mycyfapp.eu). These results have contributed to the development of a mobile app for cystic fibrosis patients, which includes an algorithm for enzyme dose prediction based on food properties. The app is currently being tested in a clinical trial setting.