The effects of cholecalciferol and afamelanotide on vitamin D levels in erythropoietic protoporphyria; a multicentre cohort study.

BACKGROUND: Erythropoietic protoporphyria (EPP) patients experience lifelong painful photosensitivity resulting in a lack of sunlight exposure. Previous studies have shown that 47-63% of EPP patients suffer from vitamin D deficiency and a high prevalence of osteoporosis. As of 2016 an effective treatment for EPP is available: the alpha-MSH analogue afamelanotide. So far studies on vitamin D levels in EPP have only investigated patients who were not treated with afamelanotide. OBJECTIVES: To investigate the effects of afamelanotide treatment on vitamin D levels in EPP. METHODS: A multi-centre observational cohort study, in adult patients with EPP from the Erasmus Medical Centre, the Netherlands and the University Hospital Düsseldorf, Germany. Routinely-collected vitamin D levels between 2005 and 2021 were used for analysis. Patient exposure to cholecalciferol or afamelanotide was categorized into four treatment groups; untreated, cholecalciferol, afamelanotide, and combined treatment. A linear mixed model for longitudinal data was applied to measure the effect of the treatment groups, compared to the untreated, on vitamin D levels. RESULTS: A total of 230 patients and 1774 vitamin D measurements were included. Prevalence of vitamin D deficiency remained high despite afamelanotide treatment: <50 nmol/l in 71.8% of patients, and severe deficiency <30 nmol/l in 48.1%. Afamelanotide treatment alone did not lead to a significant average increase in vitamin D levels (ß:0.5, 95% Confidence Interval [CI]: -3.2 - 4.2). In contrast, cholecalciferol and combined therapy with afamelanotide, led to a significant increase in vitamin D levels (ß:11.6, CI: 7.2-15.9 and ß:15.2, CI: 12.3-18.1). CONCLUSION: Cholecalciferol remains essential for treatment of vitamin D deficiency in EPP, irrespective of new treatment options like afamelanotide. Afamelanotide treatment did not affect vitamin D levels. We suggest that future guidelines include continuous monitoring of vitamin D and prescription of cholecalciferol in all patients with EPP, including those treated with afamelanotide.

OCT Evaluation of Marginal and Internal Interface Integrity of Class V Composite Restorations after 36 to 48 Months.

PURPOSE: To compare a self-etch and a two-step etch-and-rinse adhesive in terms of internal and marginal composite-tooth bond failure separately on enamel and dentin/cement at 36-48 months after restoration placement using optical coherence tomography (OCT). MATERIALS AND METHODS: Twenty-seven patients with two or three class V composite restorations of noncarious cervical lesions 36-48 months after placement were included. The one-step self-etch adhesive Futurabond M ([Voco] group SE, n = 25) and the two-step etch-and-rinse adhesive Solobond M ([Voco] group ER, n = 20) combined with the nanohybrid composite Amaris (Voco) were evaluated. The four-step etch-and-rinse adhesive Syntac classic combined with Tetric EvoCeram (Ivoclar Vivadent) served as the control (n = 18). Spectral-domain OCT (SD-OCT, 1310-nm center wavelength) was applied. Marginal gaps and internal interfacial adhesive defects were quantified in cross-sectional OCT images. Groups were statistically compared using the Friedman/Wilcoxon test (α = 0.05). RESULTS: In enamel, nonsignificantly different percentages of marginal gap formation and internal interfacial adhesive defects were found between the groups (pi ≥ 0.258). In dentin/cement, SE showed significantly less marginal gap formation compared to ER (p < 0.001) and control (p = 0.001), and at the internal dentin-composite interface less adhesive defects were found compared to ER (p < 0.001) and control (p = 0.003). CONCLUSION: The self-etch adhesive used in the current study appears recommendable for restoration of noncarious cervical lesions with composite.

Fatigue in patients with inflammatory bowel disease is associated with distinct differences in immune parameters.

BACKGROUND: Although it is well recognized that fatigue is an important problem in many of the quiescent inflammatory bowel disease (IBD) patients, it is unknown whether the immune status is different in fatigued versus non-fatigued patients. In this study, we contrasted various characteristics of the immune system in fatigued against non-fatigued patients with IBD in clinical remission. PATIENTS AND METHODS: Patients with IBD in clinical remission were phenotyped according to the Montreal classification, and the checklist individual strength-fatigue (CIS-fatigue) was used to assess fatigue (CIS-fatigue ≥ 35). Flow cytometry on peripheral blood samples was used to investigate differences in leukocyte subsets. The expression of various cytokines was determined in stimulated whole blood and serum samples using enzyme-linked immunosorbent assay. Differences between fatigued and non-fatigued patients with IBD were assessed. RESULTS: In total, 55 patients were included in the fatigue group (FG) and 29 patients in the non-fatigue group (NFG). No differences in demographic and clinical characteristics were observed between the groups. Flow cytometry data showed a significantly lower percentage of monocytes (p = 0.011) and a higher percentage of memory T-cells (p = 0.005) and neutrophils (p = 0.033) in the FG compared with the NFG. Whole blood stimulation showed increased TNF-α (p = 0.022) and IFN-γ (p = 0.047) in the FG. The median serum level was significantly higher for IL-12 (p < 0.001) and IL-10 (p = 0.005) and lower for IL-6 (p = 0.002) in the FG compared with NFG. CONCLUSION: Significant differences in immune profile between fatigued and non-fatigued patients with IBD in clinical remission were found, which point out to a chronically active and Th1-skewed immune system in patients with fatigue. Whether these immune differences are directly involved in the fatigue complaints via immune-to-brain communication pathways remains to be determined. As such, further exploration of the underlying immune effects associated with fatigue is warranted to determine potential treatment options.