International Journal of Dermatology最新文献

Vitiligo is a common depigmentation disorder classified into nonsegmental vitiligo (NSV) and segmental vitiligo (SV). SV accounts for 5-27.9% of patients with vitiligo. The primary pathogenesis of NSV involves the autoimmune-mediated destruction of melanocytes. Recently, an autoimmune pathogenesis of SV was identified. High levels of melanocyte antigen-specific CD8+ T cells are found in early SV lesional skin infiltrating around melanocytes along the basal layer. Mixed vitiligo suggests an overlap in pathogenesis between SV and NSV. In active SV, serum innate immune cytokines, and CD8+ T cell cytokines are increased. Oxidative stress in SV may activate autoimmune responses. SV pathogenesis is associated with a local cytotoxic response targeting epidermal melanocytes. Theories have been put forward to explain the segmental pattern in SV. The previous basis of the neurogenic theory that SV results from dermatomes is no longer accepted. However, there are still research reports supporting this theory. Evaluating the distribution pattern of SV lesions has provided clues to the mosaicism detection of suspected melanocytic defects at the site of SV lesions, supporting this theory. Evidence points to a cytotoxic response targeting mosaic melanocytes. Understanding SV's autoimmune pathogenesis prompts a reevaluation of immunosuppressive medical treatments for SV. The excellent results of autologous melanocyte transplantation in SV lesions compared with the moderate to limited results in patients with NSV support the mosaicism theory.

Background: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem.

Objective: Here, we mine large-scale MM proteogenomic data to identify druggable targets and forecast treatment efficacy and resistance.

Methods: Leveraging protein profiles from established MM subtypes and molecular structures of 82 cancer treatment drugs, we identified nine candidate hub proteins, mTOR, FYN, PIK3CB, EGFR, MAPK3, MAP4K1, MAP2K1, SRC, and AKT1, across five distinct MM subtypes. These proteins are potential drug targets applicable to one or multiple MM subtypes. Additionally, by integrating proteogenomic profiles obtained from MM subtypes with MM cell line dependency and drug sensitivity data, we identified a total of 162 potentially targetable genes. Lastly, we identified 20 compounds exhibiting potential drug impact in at least one melanoma subtype.

Results: Employing these unbiased approaches, we have uncovered compounds targeting ferroptosis demonstrating a striking 30× fold difference in sensitivity among different subtypes.

Conclusions: Our results suggest innovative and novel therapeutic strategies by stratifying melanoma samples through proteomic profiling, offering a spectrum of novel therapeutic interventions and prospects for combination therapy.

Background: In dermatology, the majority of opioid prescriptions occur in dermatologic surgery. Even short courses of opioids are linked to substance abuse. Reported rates of opioid prescription in dermatologic surgery are variable, with no consensus on when they should be prescribed. Little population data currently exists on opioids in dermatologic surgery and the potentially serious complications that result. Here, we use an international patient data network to evaluate trends in postoperative opioid prescription in the setting of dermatologic surgery and complications that may result.

Methods: This retrospective cohort study analyzed patients within the TriNetX research network. A total of 1,160,223 dermatologic surgery patients were extracted. Risk analyses were conducted examining (1) oral opioid prescription within 2 days postsurgery; (2) adverse events related to opioid use 3 months to 5 years postsurgery. Propensity score matching included variables: age, gender, race, ethnicity, complex regional pain syndrome, back pain, osteoarthritis, and malignancy.

Results: A total of 124,292 (13.6%) patients received postsurgical opioids. Black or African American race, female gender, and Latino ethnicity were associated with significantly higher absolute risk of postsurgical opioid prescription. A positive history of prior opioid prescription, opioid abuse or dependence, or substance abuse yielded a significant increase in the absolute risk of receiving postsurgical opioids (P < 0.0001). Patients prescribed postsurgical opioids had a statistically significantly higher risk of subsequent oral opioid prescription (P < 0.0001), opioid abuse (P = 0.0005), substance abuse (P < 0.0001), overdose by opioids (P = 0.031), constipation (P < 0.0001), and chronic pain (P < 0.0001) 3 months to 5 years after surgery.

Conclusions: This study finds female, African American, and Latino populations have a higher risk of being prescribed opioids postoperatively. This prescription may confer risks of potentially serious complications related to opioid use. Dermatologic surgeons should be aware of the risks these populations face when determining candidacy for postsurgical opioid analgesia.

Premature hair graying (PHG) is the early loss of natural hair color, influenced by genetic, biological, and environmental factors. This review discusses the significant psychological impacts of PHG and explores its underlying mechanisms, related health conditions, and available treatments. The review examines the roles of genetics, oxidative stress, and lifestyle factors such as smoking and diet in premature graying. It also considers associated medical conditions and current and emerging treatment options. This overview aims to improve understanding of PHG and its broader implications.