Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances.

Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and high mortality. Recent advances in molecular pathogenesis have shed light on genetic and epigenetic changes that drive melanoma development. This review provides an overview of these developments, focusing on molecular mechanisms in melanoma genesis. It highlights how mutations, particularly in the BRAF, NRAS, c-KIT, and GNAQ/GNA11 genes, affect critical signaling pathways. The evolution of diagnostic techniques, such as genomics, transcriptomics, liquid biopsies, and molecular biomarkers for early detection and prognosis, is also discussed. The therapeutic landscape has transformed with targeted therapies and immunotherapies, improving patient outcomes. This paper examines the efficacy, challenges, and prospects of these treatments, including recent clinical trials and emerging strategies. The potential of novel treatment strategies, including neoantigen vaccines, adoptive cell transfer, microbiome interactions, and nanoparticle-based combination therapy, is explored. These advances emphasize the challenges of therapy resistance and the importance of personalized medicine. This review underlines the necessity for evidence-based therapy selection in managing the increasing global incidence of melanoma.

Risk of Subsequent Vitiligo in Transplant Recipients With Comorbid Graft-vs-Host Disease.

Importance: Vitiligo is a multifactorial, depigmenting skin disorder characterized by selective loss of melanocytes. Large-scale studies are lacking to determine the risk of vitiligo in transplant recipients with graft-vs-host disease (GVHD). Objective: To investigate the incidence rates and risk of vitiligo in patients who had received solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT) overall and by HSCT graft type and concomitant GVHD. Design, Setting, and Participants: This population-based cohort study included data from the National Health Insurance Service database of Korea for patients aged 20 years or older who had received a transplant (SOT or HSCT) between January 2010 and December 2017, with follow-up until December 2019. A cohort of age- and sex-matched (1:5) control individuals who did not receive a transplant was included for comparison. Data were analyzed from July 2021 to December 2021. Exposure: Transplant (SOT or HSCT) and GVHD. Main Outcomes and Measures: The main outcome was risk of vitiligo, assessed using multivariable Cox proportional hazards regression analyses adjusting for potential confounding factors. Results: The study included 23 829 patients who had undergone SOT or HSCT (62.78% male; mean [SD] age, 49.58 [11.59] years) and 119 145 age- and sex-matched controls. Patients who had undergone transplant had a significantly higher risk of vitiligo compared with controls (adjusted hazard ratio [AHR], 1.73; 95% CI, 1.35-2.22). Risk of vitiligo was also slightly higher in kidney transplant recipients and liver transplant recipients compared with the controls but was highest in HSCT recipients (AHR, 12.69; 95% CI, 5.11-31.50). Patients who had received allogeneic grafts (AHR, 14.43; 95% CI, 5.61-37.15), those who had received autologous grafts (AHR, 5.71; 95% CI, 1.20-3.18), those with comorbid GVHD (AHR, 24.09; 95% CI, 9.16-63.35), and those without GVHD (AHR, 8.21; 95% CI, 3.08-21.87) had a higher risk of vitiligo compared with controls. Conclusion and Relevance: In this study, risk of vitiligo was significantly higher in transplant recipients, especially in HSCT recipients and those with allogeneic grafts or comorbid GVHD. These findings provide new insights into the association between the risk of vitiligo and transplant and GVHD. Clinicians should be aware of these risks, implementing a multidisciplinary approach for monitoring.

Adult-Onset Subungual Eccrine Angiomatous Hamartoma on Right Great Toe: A Case Report.

Eccrine angiomatous hamartoma (EAH) is a benign skin nodule characterized by the proliferation of eccrine glands and vascular structures in the dermis. It usually presents as a single papule or nodule on the extremities, and usually arises at birth or in early childhood, but several cases which appeared in adulthood have been reported. A 52-year-old female presented with a tender subungual nodule on the right great toenail for 3 months. Skin biopsy from the lesion showed proliferation of eccrine glands and capillaries in the dermis, and immunohistochemistry confirmed the diagnosis of EAH. We excised it as a treatment, and at the 3-month follow-up, pain by her lesion has resolved without any adverse effects. Our presented case is an adult-onset EAH that occurred as a subungual lesion. Unlike the previous cases, it did not cause any nail deformity or destruction and initially was misinterpreted as some other subungual tender nodule. To the best of our knowledge, we report the first case of adult-onset subungual EAH without nail deformity.

Hormone Replacement Therapy and Psoriasis Risk: A Nationwide Population-Based Cohort Study.

BACKGROUND: Hormone replacement therapy (HRT) is used to relieve menopause symptoms, but has been reported to be associated with coronary heart disease and cancers in women. However, a link between HRT and psoriasis has yet to be established. The aim of this study was to determine the association between HRT and the risk of psoriasis. METHODS: We executed a nationwide population-based study. A total of 1,130,741 post-menopause women were enrolled in the national health care insurance database based on the enrollment criteria. The study population was classified into four groups based on the duration of the HRT, and the risk of psoriasis was analyzed. RESULTS: The incidence rates of psoriasis per 1,000 person-years were 3.36 and 4.09 in the no history of HRT and ≥ 5 years of HRT, respectively. After adjustment for age, smoking, alcohol intake, regular exercise, body mass index, diabetes mellitus, hypertension, and dyslipidemia, the most prolonged duration of the HRT group (≥ 5 years) exhibited significantly increased risk of developing psoriasis (hazard ratio, 1.22; 95% confidence interval, 1.16-1.29). CONCLUSION: We propose that HRT in post-menopausal women is associated with an increased likelihood of psoriasis development.

Molecular Characterization of Filenchus cylindricus (Thorne & Malek, 1968) Niblack & Bernard, 1985 (Tylenchida: Tylenchidae) from Korea, with Comments on Its Morphology.

Filenchus cylindricus (Thorne & Malek, 1968) Niblack & Bernard, 1985 was reported from the sandy rhizospheric soils of Poa pratensis and for the first time in Korea. Females and males are molecularly characterized and morphological and morphometric data supplied. Identification was made using an integrative approach considering morphological characteristics and inferences drawn from the analyses of the D2-D3 expansion segment of 28S rRNA and ITS1-5.8S-ITS2 of rRNA partial sequences. Females and males from Korea conform to the type descriptions and also to subsequent species descriptions from Iowa and Colorado USA, Sudan and Pakistan. Despite the close morphological and morphometric similarities with F. thornei (Andrássy, 1954) Andrássy, 1963, the two species can be adequately differentiated based on molecular data inference.

Risk factors of dermatophytosis among Korean adults.

Dermatophytosis includes all fungal infections caused by dermatophytes in humans. Some risk factors for the development of subtypes of dermatophytosis have been studied; however, large-scale epidemiologic studies on risk factors for total dermatophytosis are scarce. We investigated the risk factors of dermatophytosis using a nationwide study. Total 4,532,655 subjects with dermatophytosis aged between 20 and 40 years were examined using data from the Korean National Health Insurance Service from 2009 to 2018. Women showed a lower risk of development of dermatophytosis compared to men [hazard ratio (HR) 0.848; 95% confidence interval (CI) 0.843-0.853]. Subjects with elevated waist circumference (HR 1.057; 95% CI 1.048-1.065), heavy drinking (HR 1.053; 95% CI 1044-1.061), engaging in mild-to-heavy exercise (HR 1.071; 95% CI 1.064-1.077) had a higher risk of dermatophytosis. In addition, subjects with body mass index (BMI) of more than 30 kg/m2 exhibited a higher risk of dermatophytosis (HR 1.36; 95% CI 1.342-1.378) compared to those with BMIs in the range of 18.5-23 kg/m2. In this study, the risk of developing dermatophytosis significantly increased in individuals with elevated waist circumference or high BMI. Lifestyle modifications, including weight management, are suggested to be important in preventing dermatophytosis.

Treatment of Actinic Keratosis: The Best Choice through an Observational Study.

Actinic keratosis (AK) is a precancerous lesion that can progress to invasive squamous cell carcinoma if untreated. However, no gold standard treatment has been established. We aimed to investigate the management of AK by comparing the effectiveness and treatment duration of treatment modalities, including cryotherapy, imiquimod (IMQ), and photodynamic therapy (PDT). We reviewed the medical records of 316 patients diagnosed with AK at Seoul St. Mary's Hospital from February 2015 to May 2020, and a total of 195 patients were included. The clearance rate was the highest in PDT, followed by cryotherapy and IMQ (82.4%, 71.2%, and 68.0%, respectively). The recurrence rate was the lowest in cryotherapy, followed by PDT and IMQ (3.5%, 6.7%, and 10.5%, respectively, p < 0.05). The average treatment duration was shortest with PDT, followed by IMQ and cryotherapy (5.5 weeks, 6.8 weeks, and 9.1 weeks, respectively, p < 0.05). The number of hospital visits was lowest for PDT, followed by cryotherapy and IMQ (1.8, 2.8, and 3.6, respectively, p < 0.05). PDT showed the highest clearance rate, a moderate recurrence rate, the shortest treatment duration, and the least number of visits, suggesting that PDT could be the first choice for treatment of AK. Considering the advantages as a topical agent, IMQ could also be a treatment option.

Risk for Behçet's disease gauged via high-density lipoprotein cholesterol: a nationwide population-based study in Korea.

Behçet's disease (BD) is a chronic inflammatory disease. Low levels of plasma high-density lipoprotein cholesterol (HDL-C) are associated with Crohn's disease, another chronic inflammatory disease. However, the effects of low HDL-C levels on BD are unclear. We investigated the effects of HDL-C levels, and variability therein, on the risk for BD. We used the Korean National Health Insurance System database to identify 5,587,754 adults without a history of BD who underwent ≥ 3 medical examinations between 2010 and 2013. Mean HDL-C levels at each visit were used to calculate variability independent of the mean (VIM) and the coefficient of variation (CV). There were 676 new cases of BD (0.012%). The risk for BD was increased in participants with highly variable and low mean HDL-C levels. In a multivariate-adjusted model, the hazard ratios (95% confidence intervals) for BD incidence were 1.335 (1.058-1.684) in a high mean/high VIM group, 1.527 (1.211-1.925) in a low mean/low VIM group, and 2.096 (1.67-2.63) in a low mean/high VIM group compared to a high mean/low VIM group. Low mean HDL-C levels, and high variability therein, are independent risk factors for BD.

Analysis on the Effectiveness and Characteristics of Treatment Modalities for Bowen's Disease: An Observational Study.

Treatment options for Bowen's disease (BD) include surgical excision, cryotherapy, curettage with cautery, topical 5-fluorouracil or imiquimod, and photodynamic therapy. However, it is not clear which treatment is the most effective due to lack of studies. We reviewed the electronic medical records of 158 patients who were diagnosed with BD and treated at Seoul St. Mary's Hospital from January 2011 to December 2020. Treatment modalities were surgical excision, cryotherapy, photodynamic therapy, and imiquimod. A total of 121 patients was enrolled in this study. The average treatment period was longest for cryotherapy, followed by imiquimod, PDT, and excision (119.53, 87.75, 68.50, and 1 day, respectively). The therapeutic efficacy was highest in the surgical excision group (100%) and lowest in the PDT group (62.5%). The recurrence rate was highest in the imiquimod group (33.33%). Surprisingly, only in patients treated with cryotherapy, satellite lesions developed in 9.09% of them during follow-up. Surgical excision exhibited the highest clearance rate and the lowest recurrence rate, and its treatment period was the shortest, confirming that it remains the gold standard. In contrast, since cryotherapy demonstrated a relatively high recurrence rate including development of satellite lesions, careful monitoring is required when performing cryotherapy for treatment of BD.

Inhibitory effects of superoxide dismutase 3 on IgE production in B cells.

Immunoglobulin E (IgE) functions as a first-line defense against parasitic infections. However, aberrant production of IgE is known to be associated with various life-threatening allergic diseases. Superoxide dismutase 3 (SOD3) has been found to suppress IgE in various allergic diseases such as allergic conjunctivitis, ovalbumin-induced allergic asthma, and dust mite-induced atopic dermatitis-like skin inflammation. However, the role of SOD3 in the regulation of IgE production in B cells remains elusive. In this study, we investigated the effect of SOD3 on LPS/IL-4 and anti-CD40/IL-4-mediated secretion of IgE in murine B cells. Our data showed that SOD3 can suppress both LPS/IL-4 and antiCD40/IL-7-induced IgE secretion in B cells isolated from both wild-type (SOD3 +/+ ) and SOD3 knock-out (SOD3 -/- ) mice. Interestingly, B cells isolated from SOD3 -/- mice showed higher secretion of IgE, whereas, the use of DETCA, a known inhibitor of SOD3 activity, reversed the inhibitory effect of SOD3 on IgE production. Similarly, SOD3 was found to reduce the proliferation, IgE isotype switch, ROS level, and CCL17 and CCL22 productions in B cells. Furthermore, SOD3 was found to suppress both LPS/IL-4 and anti-CD40/IL-4-mediated activation of downstream signaling such as JAK1/JAK3, STAT6, NF-κB, p38, and JNK in B cells. Taken together, our data showed that SOD3 can be used as an alternative therapy to restrict IgE-mediated allergic diseases.