Clinical, histopathological and immunohistochemical evaluation of ultraviolet A1 treatment in early-stage mycosis fungoides.

BACKGROUND/PURPOSE: Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphomas primarily involving the skin. Early-stage MF is characterised by non-specific skin lesions and non-diagnostic biopsies. While skin-focused treatments, such as PUVA and narrowband UVB (nbUVB), are the most frequently recommended treatments, the UVA1 efficacy has been researched in recent years. The purpose of this study was to evaluate the clinical, histopathological and immunohistochemical aspects of UVA1 treatment in patients with early-stage MF. METHODS: The modified severity weighted assessment scale (mSWAT) was used for total skin body scoring before and after treatment. Skin punch biopsies were taken from the patients before and after treatment. UVA1 therapy was performed five times each week. RESULTS: This study included 26 patients with early-stage MF. The total number of UVA1 sessions varied between 15 and 34. Complete response was observed in 8 (30.8%) of 26 patients (30.8%). The median mSWAT score decreased statistically significantly from 7.1 to 2.0 after treatment (p < .001). Histopathological complete response was observed in 2 (9.5%) of 21 patients. A statistically significant decrease in dermal interstitial infiltrate was observed on histopathological examination after treatment (p = .039). Epidermal CD4/CD8 levels decreased statistically significantly higher from a median of 2.5-1.2 in the complete clinical response group after treatment (p = .043). CONCLUSION: According to our results, UVA1 treatment has an effect on early-stage MF in terms of clinical, histopathological and immunohistochemistry.

Biological therapy management from the initial selection of biologics to switching between biologics in severe asthma.

The aim of this review is to elaborate the management of biologic therapy from initial selection to switching biologics in severe asthma. A nonsystematic review was performed for biological therapy management in severe asthma. Depending on clinical characteristics and biomarkers, selecting the preferred biologic based on super-responder criteria from previous studies may result in adequate clinical efficacy in most patients. On the other hand, no matter how carefully the choice is made, in some patients, it may be necessary to discontinue the drug due to suboptimal clinical response or even no response. This may result in the need to switch to a different biological therapy. How long the biological treatment of patients whose asthma is controlled with biologics will be continued and according to which criteria they will be terminated remains unclear. It has been shown that in patients with a long history of good response to biologics, asthma control may be impaired when biologics are discontinued, while it may persist in others. Therefore, discontinuation of biologics may be a viable strategy in a particular patient group. Clinicians should make the best use of all predictive factors to identify patients who will most benefit from each biologic. Patients who do not meet a predefined response criterion after sufficient time for response evaluation and who are eligible for one or more alternative biological agents should be offered the opportunity to switch to another biologic. There is no consensus on when the biologics used in severe asthma that produce favorable results should be discontinued. In our opinion, treatment should continue for at least five years, as premature termination may potentially deteriorate asthma control.

Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density.

The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease.