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1.
Vitamin D and prebiotics for intestinal health in cystic fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 x 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D trial) in adults with cystic fibrosis.
Sivapiromrat, AK, Suppakitjanusant, P, Wang, Y, Hu, C, Binongo, J, Hunt, WR, Weinstein, S, Jathal, I, Alvarez, JA, Chassaing, B, et al
Contemporary clinical trials communications. 2024;:101278
Abstract
Individuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI and airway dysbiosis. Thus, a 2 x 2 factorial design, placebo-controlled, double-blinded, pilot and feasibility, clinical trial was proposed to test this hypothesis. Forty adult participants with CF were block-randomized into one of four groups: 1) high-dose oral vitamin D3 (50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3 weekly; 3) combined oral vitamin D3 weekly and oral prebiotic inulin daily; and 4) oral vitamin D3 placebo weekly and oral prebiotic placebo. The primary endpoints included 12-week changes in the microbial bacterial communities, gut and airway microbiota richness and diversity before and after the intervention. This pilot study examined whether vitamin D3 with or without prebiotics supplementation was feasible, changed airway and gut microbiota, and reduced dysbiosis, which in turn, may improve health outcomes and quality of life of patients with CF.
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2.
Maternal and Offspring Fatty Acid Desaturase Variants, Prenatal DHA Supplementation, and Dietary n-6:n-3 Fatty Acid Ratio in Relation to Cardiometabolic Health in Mexican Children.
Wimalasena, ST, Ramírez Silva, CI, Gonzalez Casanova, I, Rivera, JA, Sun, YV, Stein, AD, Ferranti, EP, Alvarez, JA, Demmelmair, H, Koletzko, B, et al
The Journal of nutrition. 2024
Abstract
BACKGROUND Single-nucleotide polymorphisms (SNPs) in fatty acid desaturase (FADS) genes may modify dietary fatty acid requirements and influence cardiometabolic health (CMH). OBJECTIVES We evaluated the role of selected variants in maternal and offspring FADS genes on offspring CMH at the age of 11 y and assessed interactions of genotype with diet quality and prenatal docosahexaenoic acid (DHA) supplementation. METHODS We used data from offspring (n = 203) born to females who participated in a randomized controlled trial of DHA supplementation (400 mg/d) from midgestation to delivery. We generated a metabolic syndrome (MetS) score from body mass index, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and fasting glucose and identified 6 distinct haplotypes from 5 offspring FADS SNPs. Dietary n-6 (ω-6):n-3 fatty acid ratios were derived from 24-h recall data (n = 141). We used generalized linear models to test associations of offspring diet and FADS haplotypes with MetS score and interactions of maternal and offspring FADS SNP rs174602 with prenatal treatment group and dietary n-6:n-3 ratio on MetS score. RESULTS Associations between FADS haplotypes and MetS score were null. Offspring SNP rs174602 did not modify the association of prenatal DHA supplementation with MetS score. Among children with TT or TC genotype for SNP rs174602 (n = 88), those in the highest n-6:n-3 ratio tertile (>8.61) had higher MetS score relative to the lowest tertile [<6.67) (Δ= 0.36; 95% confidence interval (CI): 0.03, 0.69]. Among children with CC genotype (n = 53), those in the highest n-6:n-3 ratio tertile had a lower MetS score relative to the lowest tertile (Δ= -0.23; 95% CI: -0.61, 0.16). CONCLUSIONS There was evidence of an interaction of offspring FADS SNP rs174602 with current dietary polyunsaturated fatty acid intake, but not with prenatal DHA supplementation, on MetS score. Further studies may help to determine the utility of targeted supplementation strategies and dietary recommendations based on genetic profile.
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3.
Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 × 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D Trial) in adults with cystic fibrosis.
Sivapiromrat, AK, Suppakitjanusant, P, Wang, Y, Binongo, J, Hunt, WR, Gewirtz, A, Alvarez, JA, Hu, C, Weinstein, S, Jathal, I, et al
medRxiv : the preprint server for health sciences. 2024
Abstract
Individuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI dysbiosis and improving intestinal functions. Thus, a 2 × 2 factorial design, placebo-controlled, double-blind, clinical trial was proposed to test this hypothesis. Forty adult participants with CF will be block-randomized into one of four groups: 1) high-dose oral vitamin D3 (50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3 weekly; 3) combined oral vitamin D3 weekly and oral prebiotic inulin daily; and 4) oral vitamin D3 placebo weekly and oral prebiotic placebo. The primary endpoints will include 12-week changes in the reduced relative abundance of gammaproteobacteria, and gut microbiota richness and diversity before and after the intervention. This clinical study will examine whether vitamin D3 with or without prebiotics will improve intestinal health and reduce GI dysbiosis, which in turn, should improve health outcomes and quality of life of patients with CF.
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4.
Vitamin D for glycemic control following an acute pulmonary exacerbation: A secondary analysis of a multicenter, double-blind, randomized, placebo-controlled trial in adults with cystic fibrosis.
Sivapiromrat, AK, Hunt, WR, Alvarez, JA, Ziegler, TR, Tangpricha, V
medRxiv : the preprint server for health sciences. 2024
Abstract
Individuals with cystic fibrosis (CF) often incur damage to pancreatic tissue due to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein, leading to altered chloride transport on epithelial surfaces and subsequent development of cystic fibrosis-related diabetes (CFRD). Vitamin D deficiency has been associated with the development of CFRD. This was a secondary analysis of a multicenter, double-blind, randomized, placebo-controlled study in adults with CF hospitalized for an acute pulmonary exacerbation (APE), known as the Vitamin D for the Immune System in Cystic Fibrosis (DISC) trial (NCT01426256). This was a pre-planned secondary analysis to examine if a high-dose bolus of cholecalciferol (vitamin D3) can mitigate declined glucose tolerance commonly associated with an acute pulmonary exacerbation (APE). Glycemic control was assessed by hemoglobin A1c (HbA1c) and fasting blood glucose levels before and 12 months after the study intervention. Within 72 hours of hospital admission, participants were randomly assigned to a single dose of oral vitamin D3 (250,000 IU) or placebo, and subsequently, received 50,000 IU of vitamin D3 or placebo every other week, beginning at month 3 and ending on month 12. Forty-nine of the 91 participants in the parent study were eligible for the secondary analysis. There were no differences in 12-month changes in HbA1c or fasting blood glucose in participants randomized to vitamin D or placebo. A high-dose bolus of vitamin D3 followed by maintenance vitamin D3 supplementation did not improve glycemic control in patients with CF after an APE.
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5.
Correction: The effect of a single, large bolus of vitamin D in healthy adults over the winter and following year: a randomized, double-blind, placebo-controlled trial.
Kearns, MD, Binongo, JNG, Watson, D, Alvarez, JA, Lodin, D, Ziegler, TR, Tangpricha, V
European journal of clinical nutrition. 2023;(6):698
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6.
Cystic Fibrosis-Related Diabetes Workshop: Research Priorities Spanning Disease Pathophysiology, Diagnosis, and Outcomes.
Putman, MS, Norris, AW, Hull, RL, Rickels, MR, Sussel, L, Blackman, SM, Chan, CL, Ode, KL, Daley, T, Stecenko, AA, et al
Diabetes. 2023;(6):677-689
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Free full text
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Abstract
Cystic fibrosis (CF) is a recessive disorder arising from mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR is expressed in numerous tissues, with high expression in the airways, small and large intestine, pancreatic and hepatobiliary ducts, and male reproductive tract. CFTR loss in these tissues disrupts regulation of salt, bicarbonate, and water balance across their epithelia, resulting in a systemic disorder with progressive organ dysfunction and damage. Pancreatic exocrine damage ultimately manifests as pancreatic exocrine insufficiency that begins as early as infancy. Pancreatic remodeling accompanies this early damage, during which abnormal glucose tolerance can be observed in toddlers. With increasing age, however, insulin secretion defects progress such that CF-related diabetes (CFRD) occurs in 20% of teens and up to half of adults with CF. The relevance of CFRD is highlighted by its association with increased morbidity, mortality, and patient burden. While clinical research on CFRD has greatly assisted in the care of individuals with CFRD, key knowledge gaps on CFRD pathogenesis remain. Furthermore, the wide use of CFTR modulators to restore CFTR activity is changing the CFRD clinical landscape and the field's understanding of CFRD pathogenesis. For these reasons, the National Institute of Diabetes and Digestive and Kidney Diseases and the Cystic Fibrosis Foundation sponsored a CFRD Scientific Workshop, 23-25 June 2021, to define knowledge gaps and needed research areas. This article describes the findings from this workshop and plots a path for CFRD research that is needed over the next decade.
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7.
Cystic Fibrosis-Related Diabetes Workshop: Research Priorities Spanning Disease Pathophysiology, Diagnosis, and Outcomes.
Putman, MS, Norris, AW, Hull, RL, Rickels, MR, Sussel, L, Blackman, SM, Chan, CL, Ode, KL, Daley, T, Stecenko, AA, et al
Diabetes care. 2023;(6):1112-1123
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Free full text
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Abstract
Cystic fibrosis (CF) is a recessive disorder arising from mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR is expressed in numerous tissues, with high expression in the airways, small and large intestine, pancreatic and hepatobiliary ducts, and male reproductive tract. CFTR loss in these tissues disrupts regulation of salt, bicarbonate, and water balance across their epithelia, resulting in a systemic disorder with progressive organ dysfunction and damage. Pancreatic exocrine damage ultimately manifests as pancreatic exocrine insufficiency that begins as early as infancy. Pancreatic remodeling accompanies this early damage, during which abnormal glucose tolerance can be observed in toddlers. With increasing age, however, insulin secretion defects progress such that CF-related diabetes (CFRD) occurs in 20% of teens and up to half of adults with CF. The relevance of CFRD is highlighted by its association with increased morbidity, mortality, and patient burden. While clinical research on CFRD has greatly assisted in the care of individuals with CFRD, key knowledge gaps on CFRD pathogenesis remain. Furthermore, the wide use of CFTR modulators to restore CFTR activity is changing the CFRD clinical landscape and the field's understanding of CFRD pathogenesis. For these reasons, the National Institute of Diabetes and Digestive and Kidney Diseases and the Cystic Fibrosis Foundation sponsored a CFRD Scientific Workshop, 23-25 June 2021, to define knowledge gaps and needed research areas. This article describes the findings from this workshop and plots a path for CFRD research that is needed over the next decade.
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8.
Diagnostic Accuracy of the RDW for Predicting Death in COVID-19.
Guaní-Guerra, E, Torres-Murillo, B, Muñoz-Corona, C, Rodríguez-Jiménez, JC, Macías, AE, Scavo-Montes, DA, Alvarez, JA
Medicina (Kaunas, Lithuania). 2022;(5)
Abstract
Background and Objectives: An association between high red blood cell distribution width (RDW) and mortality has been found in several diseases, including infection and sepsis. Some studies have aimed at determining the association of elevated RDW with adverse prognosis in COVID-19, but its usefulness has not been well established. The objective of this study was to determine the accuracy of the RDW, measured at hospital admission and discharge, for predicting death in patients with COVID-19. Materials andMethods: An observational, retrospective, longitudinal, and analytical study was conducted in two different COVID-19 reference centers in the state of Guanajuato, Mexico. A total of 323 patients hospitalized by COVID-19 were included. Results: We found higher RDW levels at the time of hospital admission in the non-survivors group compared to levels in survivors (median = 13.6 vs. 13.0, p < 0.001). Final RDW levels were even higher in the deceased group when compared with those of survivors (median = 14.6 [IQR, 12.67−15.6] vs. 12.9 [IQR, 12.2−13.5], p < 0.001). For patients who died, an RDW > 14.5% was more common at the time of death than for patients who survived at the time of discharge (81 vs. 13 patients, p < 0.001; RR = 2.3, 95% CI 1.89−2.81). Conclusions: The RDW is an accessible and economical parameter that, together with other characteristics of the presentation and evolution of patients with COVID-19, can be helpful in determining the prognosis. An RDW that increases during hospitalization could be a more important mortality predictor than the RDW at hospital admission.
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Effect of CFTR Modulators on Anthropometric Parameters in Individuals with Cystic Fibrosis: An Evidence Analysis Center Systematic Review.
Bailey, J, Rozga, M, McDonald, CM, Bowser, EK, Farnham, K, Mangus, M, Padula, L, Porco, K, Alvarez, JA
Journal of the Academy of Nutrition and Dietetics. 2021;(7):1364-1378.e2
Abstract
There is a strong positive association between nutrition status and lung function in cystic fibrosis (CF). Improvements in clinical care have increased longevity for individuals with CF, and it is unknown how cystic fibrosis transmembrane regulator (CFTR) modulation therapy affects nutrition status over time. The objective of this systematic review of the literature was to examine anthropometric (height, weight, and body mass index [BMI; calculated as kg/m2]) and body composition outcomes of CFTR modulation therapy. A literature search of Medline (Ovid), Embase, and CINAHL (EBSCO) databases was conducted for randomized controlled trials examining the effect of CFTR modulation therapy on anthropometric and body composition parameters, published in peer-reviewed journals from January 2002 until May 2018. Articles were screened, data were synthesized qualitatively, and evidence quality was graded by a team of content experts and systematic review methodologists. Significant weight gain with ivacaftor was noted in children and adults with at least 1 copy of G551D mutation. In adults with at least 1 copy of R117H the effect of ivacaftor on BMI was not significant. Effects on BMI were mixed in adults with class II mutations taking ivacaftor with lumacaftor. There was no significant change in BMI in children homozygous for F508del who took ivacaftor with tezacaftor. Elexacaftor-tezacaftor-ivacaftor increased BMI and body weight in individuals 12 years of age and older who were hetero- or homozygous for the F508del mutation. The effect of CFTR modulation therapy on anthropometric parameters depends on the genetic mutation and the type of modulation therapy used. More research is needed to understand the long-term clinical impact of these drugs on nutritional status, including body composition and the role of dietary intake.
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10.
Dietary Macronutrient Distribution and Nutrition Outcomes in Persons with Cystic Fibrosis: An Evidence Analysis Center Systematic Review.
McDonald, CM, Bowser, EK, Farnham, K, Alvarez, JA, Padula, L, Rozga, M
Journal of the Academy of Nutrition and Dietetics. 2021;(8):1574-1590.e3
Abstract
Cystic fibrosis (CF) increases risk for undernutrition and malabsorption. Individuals with CF traditionally have been counseled to consume a high-fat diet. However, a new era of CF care has increased lifespan and decreased symptoms in many individuals with CF, necessitating a re-examination of the high-fat CF legacy diet. A literature search was conducted of Medline (Ovid), Embase, and CINAHL (EBSCO) databases to identify articles published from January 2002 to May 2018 in the English language examining the relationships between dietary macronutrient distribution and nutrition outcomes in individuals with CF. Articles were screened, risk of bias was assessed, data were synthesized narratively, and each outcome was graded for certainty of evidence. The databases search retrieved 2,519 articles, and 7 cross-sectional articles were included in the final narrative analysis. Three studies examined pediatric participants and 4 examined adults. None of the included studies reported on outcomes of mortality or quality of life. Very low certainty evidence described no apparent relationship between dietary macronutrient distribution and lung function, anthropometric measures, or lipid profile in individuals with CF. The current systematic review demonstrates wide ranges in the dietary macronutrient intakes of individuals with CF with little to no demonstrable relationship between macronutrient distribution and nutrition-related outcomes. No evidence is presented to substantiate an outcomes-related benefit to a higher fat-diet except in the context of achieving higher energy intakes in a lesser volume of food.