Background
Cystic fibrosis (CF) is a multi-organ disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Individuals with CF often have gastrointestinal (GI) dysbiosis due to chronic inflammation and antibiotic use. Previous studies suggested a role for vitamin D in reversing the GI dysbiosis found in CF.
Objective
To explore the potential role of a combination of high-dose oral cholecalciferol (vitamin D3) and fermentable dietary fiber, inulin, to impact bacterial composition, richness, and diversity of intestinal and airway microbiota in adults with CF.
Methods
This was a 2 × 2 factorial, double-blinded, placebo-controlled, randomized, pilot clinical trial in which adults with CF received oral cholecalciferol (vitamin D3) (50,000 IU/week) and/or inulin (12 g/day) for 12 weeks. Thus, there were 4 study groups (n = 10 subjects per group); 1) placebo 2) vitamin D3 3) inulin 4) vitamin D3 plus inulin. Stool and sputum samples were collected at baseline (just before) and after the intervention and were analysed using 16S ribosomal RNA gene sequencing for gut and airway microbiota composition. Statistical analyses assessed alpha and beta diversity to evaluate microbial community changes.
Results
Of a total of 254 screened participants, 40 eligible participants were randomized to one of the 4 treatment arms. Participants receiving vitamin D3 plus inulin exhibited greater changes in microbiome indexes in both intestinal and airway relative to those in the other study groups. Specific taxonomic changes supported the potential beneficial influence of this combination to mitigate both intestinal and airway dysbiosis in adults with CF.
Conclusion
This pilot study established that the combination of oral vitamin D3 and the prebiotic inulin was well tolerated over 12 weeks in adults with CF and altered gut and airway bacterial communities. Future research appear warranted to define clinical outcomes and the role of microbiota changes therein with this approach.
The goal of the study was to examine the association between depression and perceived community tolerance after controlling for various demographic and personal characteristics, treatment receipt, and past experiences with abuse or discrimination. An online survey assessed depressive symptoms among transgender and gender nonconforming individuals. Depression was assessed using the 7-item Beck Depression Inventory for Primary Care (BDI-PC) and the 10-item Center for Epidemiologic Studies Depression (CESD-10) scale. The prevalence ratios (95% confidence intervals) comparing depression in persons who did and did not perceive their area as tolerant were 0.33 (0.20–0.54) for BD-PC and 0.66 (0.49–0.89) for CESD-10. Other factors associated with depression were experience with abuse or discrimination, lower education, and unfulfilled desire to receive hormonal therapy. Depression was common in this sample of transgender and gender nonconforming individuals and was strongly and consistently associated with participants’ perceptions of community tolerance, even after adjusting for possible confounding. The association between desire to receive hormonal therapy and depression is a finding that warrants further exploration. Future research should also assess depression and changes in perception of community tolerance in transgender individuals before and after initiation of gender confirmation treatment.
Purpose of review: This review highlights recent findings in the emerging association between vitamin D and anemia through discussion of mechanistic studies, epidemiologic studies, and clinical trials.
Recent findings: Vitamin D has previously been found to be associated with anemia in various healthy and diseased populations. Recent studies indicate that the association may differ between race and ethnic groups and is likely specific to anemia of inflammation. The mechanism underlying this association involves the reduction of pro-inflammatory cytokines by vitamin D as well as the direct suppression of hepcidin mRNA transcription. There is also evidence that vitamin D may be protective against anemia by supporting erythropoiesis. Other calciotropic hormones, fibroblast growth factor 23 (FGF-23) and parathyroid hormone (PTH) have also been found to be involved in iron homeostasis and erythropoiesis.
Summary: Recent advances in our understanding the association between vitamin D and anemia suggest that maintenance of sufficient vitamin D status may be important in preventing anemia, particularly in diseases characterized by inflammation. Early clinical trials have been promising, but further research is needed to define the efficacy of vitamin D as a future approach for the treatment of anemia.
Background: Patients with cystic fibrosis (CF) may be at risk for micronutrient depletion, particularly during periods of illness and infection. The purpose of this study was to investigate serum micronutrient status over time in adults with CF initially hospitalized with a pulmonary exacerbation.
Materials and Methods: This was an ancillary study of a multicenter trial investigating the role of high-dose vitamin D supplementation in 24 adults with CF (mean age, 29.6 ± 7.3 years). We measured serum concentrations of copper (Cu), iron (Fe), calcium (Ca), magnesium (Mg), potassium (K), and sulfur (S) in subjects at the beginning of a pulmonary exacerbation and again at 3 months.
Results: Serum concentrations of Cu, Fe, and Ca were significantly lower at baseline compared with 3 months following the pulmonary exacerbation (Cu: baseline, 1.5 ± 0.6 vs 3 months, 1.6 ± 0.6 μg/mL, P = .027; Fe: 0.8 ± 0.3 vs 1.3 ± 1.1 μg/mL, P = .026; Ca: 9.7 ± 0.8 vs 10.8 ± 2.0 mg/dL, P = .024). Serum concentrations of K, Mg, and S did not change over time (K: baseline, 4.9 ± 0.3 vs 3 months, 5.1 ± 0.5 mEq/L; Mg: 1.8 ± 0.2 vs 2.0 ± 0.3 mg/dL; S: 1288.6 ± 343 vs 1309.9 ± 290 μg/mL; P > .05 for all).
Conclusion: Serum concentrations of Cu, Fe, and Ca increased significantly several months following recovery from acute pulmonary exacerbation in adults with CF. This may reflect decreased inflammation, improved food intake, and/or increased absorption following recovery.
Poor growth has long been a characteristic feature of cystic fibrosis (CF) and is significantly linked to lung function and overall health status. Improvements in pulmonary and nutrition care for patients with cystic fibrosis (CF) have resulted in better growth outcomes; however, height gains have not paralleled the improvements in weight in children with CF, and patients with more severe CF mutations remain significantly more affected. Many factors affect the growth hormone-IGF-1 axis and the growth plate of the long bones, including the chronic inflammatory state associated with CF. There are also increasing data on the direct effects of CFTR on bone and implications for CFTR modulators in attaining optimal growth. Treatments aimed at improving growth in CF are also reviewed here.
Purpose: Transgender and gender-nonconforming individuals have unique health care needs and have difficulty accessing health care services because of a lack of qualified health care providers, insurance coverage, mistreatment, and bias by the medical community. Medical trainees and physicians report a lack of education in, and exposure to, the clinical care and unique aspects of this field. We assessed the use of a standardized patient as a tool to evaluate 4 core medical competencies (patient care, medical knowledge, professionalism, and interpersonal communication) of endocrinology fellows at a single training program. Methods: Endocrine fellows were evaluated by faculty in different aspects of transgender care and completed a self-assessment before and after the exercise. Faculty viewed the fellows during the Objective Clinical Structured Examination. Fellows were provided feedback by a faculty member and the standardized patient after the exercise. Results: Deficits were found in patient care and professionalism. Fellows scored well in medical knowledge. Fellows did not report an improvement in comfort and communication skills after the exercise. Interestingly, fellows' self-assessment scores in several domains declined after the standardized patient encounter, highlighting an occasion for self-reflection and growth within the realms of cultural competency and medical knowledge. Main conclusions: We conclude that use of standardized patients to teach medical competencies in transgender medicine may be one approach to improve exposure to, and training in, transgender medicine. Endocrine fellows still had discomfort treating transgender individuals after the standardized patient encounter and require other training activities that may include didactics and clinical case discussions.
Background: Anemia, iron deficiency, and hypovitaminosis D are well-known comorbidities in inflammatory bowel disease (IBD). Epidemiologic studies have linked vitamin D deficiency with increased risk of anemia, and in vitro studies suggest that vitamin D may improve iron recycling through downregulatory effects on hepcidin and proinflammatory cytokines. Methods: We aimed to investigate the association of vitamin D status with inflammation, iron biomarkers, and anemia in pediatric IBD. Cross-sectional data were obtained from N = 69 patients with IBD aged 5 to <19 years. Iron biomarkers (ferritin, soluble transferrin receptor), and 25-hydroxyvitamin D (25(OH)D), inflammatory biomarkers (C-reactive protein and α-1-acid glycoprotein), hepcidin, and hemoglobin were collected. Iron biomarkers were regression corrected for inflammation. Multivariable logistic/linear models were used to examine the associations of 25(OH)D with inflammation, iron status, hepcidin, and anemia. Results: Approximately 50% of subjects were inflamed (C-reactive protein >5 mg/L or α-1-acid glycoprotein >1 g/L). Iron deficiency prevalence (inflammation-corrected ferritin <15 g/L or soluble transferrin receptor >8.3 mg/L) was 67%; anemia was 36%, and vitamin D insufficiency (25(OH)D <30 ng/mL) was 77%. In linear regression models, vitamin D insufficiency was associated with increased hepcidin levels (β [SE] = 0.6 [0.2], P = 0.01) and reduced hemoglobin (β [SE] = -0.9 [0.5], P = 0.046), controlling for age, sex, race, insurance status, body mass index for age, inflammation, disease diagnosis (ulcerative colitis versus Crohn's disease), and disease duration, compared with 25(OH)D ≥30 ng/mL. Conclusions: Our results suggest that concentrations of 25(OH)D ≥30 ng/mL are associated with lower hepcidin and higher hemoglobin levels. Further research is needed to clarify the association of vitamin D with inflammation, iron status, and anemia in pediatric IBD.
Post-menopausal osteoporosis is associated with estrogen deficiency and rapid bone loss. The mechanism by which estrogen deficiency results in bone loss has not been fully explained. Studies in mice rendered acutely estrogen deficient by ovariectomy have suggested that estrogen deficiency results in an activated T-lymphocyte phenotype and increased production of pro-osteoclastic cytokines. The aim of this study was to translate these findings from mouse models that suggest that the T-lymphocyte plays an important role in the etiology of post-menopausal osteoporosis. We recruited pre-menopausal women who underwent ovariectomy (OVX) for benign gynecologic conditions or for prophylaxis against ovarian cancer and a group of matched control women without OVX. Subjects provided blood samples to characterize T-lymphocyte phenotype by Fluorescence-activated cell sorting (FACS) and for T-lymphocyte culture and collection of conditioned media. Bone mineral density at the lumbar spine and left femoral neck was performed annually for two years and volumetric measurements by computed tomography (CT) of the thymus were obtained during the first 6 months. We enrolled 6 OVX and 13 control women. The OVX subjects had a significant loss of bone mineral density at the lumbar spine and left femoral neck. The volumetric thymus measurements suggested an increase in thymus size in the OVX subjects but did not reach statistical significance due to the small sample size. The T-lymphocyte phenotype in the OVX subjects demonstrated increased T-lymphocyte activation by FACS compared to the control subjects. Our preliminary findings support the hypothesis that estrogen deficiency leads to an activated T-lymphocyte phenotype which may contribute to the bone loss seen in estrogen deficiency. Larger clinical studies are necessary to confirm these findings.