Evaluation of the efficiency of nanomicellar formulation of fat-soluble vitamins in patients with cystic fibrosis: the study protocol for a randomized controlled trial.

BACKGROUND: Cystic fibrosis is an inherited disease, which is caused by the CFTR protein defects due to mutations in the CFTR gene. Along with CFTR dysfunction, exocrine pancreatic insufficiency plays a key role in persistent fat malabsorption in CF patients; therefore, deficiency of fat-soluble vitamins (A, D, E, and K) is still a therapeutic challenge. Even with efficient pancreatic enzyme medication and CF-specific vitamins, many patients with CF have fat-soluble vitamins deficiency. The present study aims to evaluate the efficiency of nanomicelle formulation of fat-soluble vitamins in children with CF in order to achieve the appropriate serum levels of these vitamins. METHODS: This prospective, single-blind control trial will be conducted at the Akbar Children's Hospital in Mashhad, Iran. Patients with CF will be enrolled based on the eligibility criteria. The control group will receive the standard formulation of fat-soluble vitamins similar to the routine CF treatment, and for the intervention group, the nanomicelle formulation of fat-soluble vitamins will be administered for 3 months. The primary outcome of this study is the measurement of serum levels of fat-soluble vitamins. The secondary outcomes are clinical assessment by the Shwachman-Kulczycki score, anthropometrics, and quality of life. Outcomes will be assessed before and after 3 months. DISCUSSION: Due to persistent fat-soluble vitamin deficiency in CF disease, the nanomicelle formulation could be proposed as a new delivery method of fat-soluble vitamins in the treatment of cystic fibrosis. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20220415054541N1. Registered on July 23, 2022.

Adjunctive nano-curcumin therapy improves inflammatory and clinical indices in children with cystic fibrosis: A randomized clinical trial.

Inflammation may develop due to internal dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein or external factors in patients with cystic fibrosis (CF). This prospective randomized clinical trial aimed to ascertain the effects of nano-curcumin as an anti-inflammatory agent and a CFTR modulator on clinical and inflammatory markers in children with CF. Children with CF were randomly assigned to receive daily curcumin or a placebo for 3 months. The primary outcome measure was to evaluate inflammatory indices, nasopharyngeal swab analysis, and clinical assessments via spirometry, anthropometric measurements, and quality of life (QOL) analysis. Sixty children were included. Intra-group changes comparison showed that curcumin decreased the level of high-sensitivity C-reactive protein (hs-CRP) (median: -0.31 mg/L, IQR: -1.53 to 0.81; p = .01) and fecal calprotectin level (-29 µg/g, -57.5 to 11.5; p = .03), also increased the level of interleukin (IL)-10 (6.1 pg/mL, 4.5-9; p = .01). Moreover, curcumin improved the overall QOL and the subscales of the questionnaire. Inter-group changes comparison depicted the number of Pseudomonas colonies reduced by about 52% in the curcumin group and gained weight by about 16% (p > .05). Nano-curcumin seems to be considered as an effective nutritional supplement on hs-CRP, IL-10, fecal calprotectin levels, and improving QOL in patients with CF.

Designing blenderized tube feeding diets for children and investigating their physicochemical and microbial properties and Dietary Inflammatory Index.

BACKGROUND: Due to the benefits of blenderized tube feeding (BTF) diets, the interest in using them is increasing. This study aimed to design BTFs for children and investigate their physicochemical and microbial properties, as well as Dietary Inflammatory Index (DII). METHODS: Five BTF diets were formulated mainly with fresh foods; their DII, physical (viscosity), and chemical (moisture, ash, protein, fat, energy, and micronutrients) characteristics were assessed. Also, the Hazard Analysis and Critical Control Points (HACCP) system was implemented for quality assurance of preparation, storage, and delivery of BTFs to patients in hospital. The microbial contamination (total count, Salmonella, Escherichia coli, Bacillus cereus, Listeria monocytogenes, coliforms, Staphylococcus aureus coagulase positive, mold, and yeast) was analyzed. RESULTS: Energy and percentages of protein, fat, and carbohydrate in BTFs were in the range of 103-112 kcal/100 ml, 16%-22%, 28%-34%, and 48%-52%, respectively. The viscosity of the five developed BTFs was between 29 and 64 centipoises, which allows the formulas to flow without syringe pressure. The DII of all BTFs was between -0.73 and -2.24. Due to the implementation of HACCP, monitoring the production line of BTFs, and performance of corrective measures, no microbial contamination was observed by indicator pathogenic microorganisms. CONCLUSION: A planned BTF diet can be an excellent selection for children using enteral nutrition with tube feeding especially when they are made from fresh and anti-inflammatory foods such as recipes prepared in this study.

Fecal Calprotectin and Phenotype Severity in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis.

Inflammation plays an important role in the outcome of patients with cystic fibrosis (CF). It may develop due to cystic fibrosis transmembrane conductance regulator protein dysfunction, pancreatic insufficiency, or prolonged pulmonary infection. Fecal calprotectin (FC) has been used as a noninvasive method to detect inflammation. Therefore, the aim of the current meta-analysis was to investigate the relationship between FC and phenotype severity in patients with CF. In this study, searches were conducted in PubMed, Science Direct, Scopus, and Embase databases up to August 2021 using terms such as "cystic fibrosis," "intestine," "calprotectin," and "inflammation." Only articles published in English and human studies were selected. The primary outcome was the level of FC in patients with CF. The secondary outcome was the relationship between FC and clinical severity. Statistical analysis was performed using Comprehensive Meta-Analysis software. Of the initial 303 references, only six articles met the inclusion criteria. The mean (95% confidence interval [CI]) level of FC was 256.5 mg/dL (114.1-398.9). FC levels were significantly associated with pancreatic insufficiency (mean, 243.02; 95% CI, 74.3 to 411.6; p=0.005; I2=0), pulmonary function (r=-0.39; 95% CI, -0.58 to -0.15; p=0.002; I2=60%), body mass index (r=-0.514; 95% CI, 0.26 to 0.69; p<0.001; I2=0%), and Pseudomonas colonization (mean, 174.77; 95% CI, 12.5 to 337.02; p=0.035; I2=71%). While FC is a reliable noninvasive marker for detecting gastrointestinal inflammation, it is also correlated with the severity of the disease in patients with CF.

Biological and pharmacological effects and nutritional impact of phytosterols: A comprehensive review.

Phytosterols (PSs), classified into plant sterols and stanols, are bioactive compounds found in foods of plant origin. PSs have been proposed to exert a wide number of pharmacological properties, including the potential to reduce total and low-density lipoprotein (LDL) cholesterol levels and thereby decreasing the risk of cardiovascular diseases. Other health-promoting effects of PSs include anti-obesity, anti-diabetic, anti-microbial, anti-inflammatory, and immunomodulatory effects. Also, anticancer effects have been strongly suggested, as phytosterol-rich diets may reduce the risk of cancer by 20%. The aim of this review is to provide a general overview of the available evidence regarding the beneficial physiological and pharmacological activities of PSs, with special emphasis on their therapeutic potential for human health and safety. Also, we will explore the factors that influence the physiologic response to PSs.

The effects of nano-curcumin as a nutritional strategy on clinical and inflammatory factors in children with cystic fibrosis: the study protocol for a randomized controlled trial.

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder, which is caused by the CFTR protein defects. Along with CFTR dysfunction, inflammation plays a key role in the disease outcomes. Inflammation may develop due to the internal dysfunction of the CFTR protein or external factors. Curcumin affects the CFTR protein function primarily as a corrector and potentiator and secondary as an anti-inflammatory and antimicrobial agent. The present study aims to assess the impact of nano-curcumin on clinical and inflammatory markers in children with CF. METHODS: This prospective, double blind control trial will be conducted at the Akbar Children's Hospital in Mashhad, Iran. Children with CF will be enrolled based on the eligibility criteria. Placebo and curcumin with the maximum dose of 80 mg considering the body surface of the patients will be administrated for 3 months. The primary outcome is to evaluate inflammation based on serum interleukin-6, interleukin-10, and hs-CRP, stool calprotectin, and neutrophil count of nasopharyngeal swab. The secondary outcome involved clinical assessment via spirometry, anthropometrics, and quality of life. They will be assessed before and after 3 months. DISCUSSION: Due to the multifarious effects of curcumin on CF disease, it could be proposed as a nutritional strategy in the treatment of cystic fibrosis. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20200705048018N1 . Registered on July 10, 2020.

Predisposing factors for nephrolithiasis and nephrocalcinosis in cystic fibrosis.

OBJECTIVE: Cystic fibrosis (CF) is characterized by chronic pulmonary disease, insufficient pancreatic and digestive function, and abnormal sweat concentration. There is controversy about predisposing factors of nephrolithiasis and nephrocalcinosis in patients with cystic fibrosis. We assessed the results of metabolic evaluation in patients with cystic fibrosis and its correlation with nephrocalcinosis. METHODS: Forty five CF patients, mean age 47.1 months, were enrolled in the study. No one had past history of nephrolithiasis and/or nephrocalcinosis. The records were reviewed for clinical characteristics and all patients underwent metabolic evaluation including serum electrolyte measurements and spot urine analysis. Ultrasonography was performed in all patients to detect nephrocalcinosis and urolithiasis. FINDINGS: Nephrocalcinosis was found in 5 (11%) patients. No patient had clinical symptoms of nephrolithiasis and/or micro/macroscopic hematuria. Metabolic evaluation of the CF patients versus normal reference values showed decreased serum uric acid in 48.8%, elevated serum phosphate in 24.4%, and urine oxalate excretion in 51%. Metabolic evaluation of the nephrocalcinosis positive patients versus nephrocalcinosis negative group showed no statistical difference in serum electrolytes. The mean value of urine calcium excretion was lower in patients with nephrocalcinosis (P=0.001). Despite lack of any significant correlation, higher numerical hyperoxaluria was observed in patients with severe steatorrhea. There was no statistical correlation between steatorrhea and urine calcium as well as oxalate excretion. CONCLUSION: Hypocalciuria in the nephrocalcinotic CF patients may be seen. It can be hypothesized that hypocalciuria may be due to a primary defect in renal calcium metabolism in CF patients.