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Abstract The relative frequency of primary cutaneous lymphoma (PCL) subtypes shows wide variation across different geographical regions. This retrospective study was conducted in a tertiary referral center located in Korea to describe the relative frequency, demographics, survival outcomes, and temporal trend in PCL. A total of 627 PCL cases diagnosed between January 1994 and December 2022 were included. The majority of PCL cases (87.2%) were of T-/NK-cell lineage (CTCL), while the remaining cases (12.8%) were B-cell lineage lymphomas (CBCL). The prevalence of mycosis fungoides (MF) in CTCL increased significantly over time, while other CTCL subtypes, including primary cutaneous extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), decreased in frequency. Notably, the prevalence of CD4-positive small/medium T-cell lymphoproliferative disorder showed a substantial increase over time. Primary cutaneous marginal zone lymphoma was consistently the commonest CBCL subtype. Survival analysis demonstrated that CTCL had a more favorable 5-year overall survival (OS) than CBCL. OS rate of MF, SPTCL, and primary cutaneous peripheral T-cell lymphoma, NOS improved significantly over time. This study provides comprehensive insights into the dynamic change in the relative frequency and overall survival of PCL subtypes over time.

Purpose Following the introduction of new type of botulinum toxin (MBA-P01), a recent phase 3 study demonstrated that MBA-P01 showed comparable efficacy and safety to onabotulinumtoxin A for reducing glabellar lines. The primary objective of this study was to evaluate the long-term safety of repeated MBA-P01 administration for the treatment of glabellar lines.Materials and methods This multicenter, single-group, repeated-dose, long-term open-label extension study evaluated repeated treatment with MBA-P01 (20 U, five treatments over 16 months), with posttreatment evaluation performed up to 52 weeks.Results Based on the safety assessment results, no specific irreversible adverse reactions were associated with the safety profile of MBA-P01. Repeated treatment with MBA-P01 was effective for a treatment duration of 3–5 months.Conclusion In conclusion, multiple cycles of treatment of glabellar lines with MBA-P01 at a dose of 20 U were well tolerated.Clinical trial registration information: This study is registered in ClincalTrials.gov (NCT05321979).

AbstractPurpose Few studies have investigated the impact of biologics on the risk of major adverse cardiovascular events (MACEs) among Korean patients with psoriatic diseases. We compared the risk of MACEs and all-cause mortality among patients with psoriatic disease treated with tumor necrosis factor (TNF)-α and interleukin (IL)-12/23 inhibitors in Korea.Methods Patients with psoriatic disease prescribed with TNF-α and IL-12/23 inhibitors since 2016 were selected from the Korean National Health Insurance Service (NHIS) Database. Follow-up data for MACEs and all-cause mortality between 2016 and 2020 were collected. A total of 2886 individuals were included, including 1987 IL-12/23 inhibitor users and 899 TNF-α inhibitor users.Results Compared with IL-12/23 inhibitor users, TNF-α inhibitor users had a higher prevalence of dyslipidemia and a significantly higher risk of all-cause mortality but not MACE. After controlling for age, female TNF-α inhibitor users had a significantly increased risk of all-cause mortality. Meanwhile, after controlling for sex, TNF-α inhibitor users aged 60 years or older demonstrated a significantly elevated risk of all-cause mortality. In conclusion, No statistically significant difference in MACE risk was observed between patients who used TNF-α and IL-12/23 inhibitors. Nevertheless, the use of IL-12/23 inhibitors, especially among older and female patients, resulted in a lower overall mortality.

Abstract Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1‐deficient mice are resistant to metastasis and further protected by combined immune‐checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF‐β1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK‐target cell responses, which is dysregulated and hijacked by tumors during metastatic progression.

Abstract Although various comorbidities have been noted to be associated with atopic dermatitis (AD) and psoriasis, few studies have compared comorbidities between the two diseases, and little is known about whether these comorbidities vary by the subtypes of psoriasis. In this study of 1:1 age- and sex-matched pair analysis between patients diagnosed with either psoriasis or AD at Asan Medical Center between 1991 and 2020, comorbidities, as determined by the International Classification of Diseases-10 codes, and likelihood ratios of metabolic and neurologic comorbidities in psoriasis compared with AD were studied using a logistic regression model. Among a total of 14,128 patients, the psoriasis group had higher odds of obesity (odds ratio [95% confidence interval]: 1.49 [1.34–1.66]), hypertension (1.14 [1.03–1.26]), diabetes mellitus (1.46 [1.29–1.66]), chronic kidney disease (1.59 [1.22–2.08]), and Parkinson's disease (2.1 [1.15–3.83]) than the AD group. Subgroup analysis revealed that patients with plaque psoriasis had higher odds of obesity (1.18 [1.05–1.33]), hypertension (1.18 [1.06–1.32]), diabetes mellitus (1.53 [1.34–1.75]), chronic kidney disease (1.66 [1.26–2.17]), and Parkinson’s disease (2.12 [1.16–3.88]) compared with AD. Meanwhile, guttate psoriasis was associated with higher odds of dementia (3.63 [1.06–12.40]) and patients with generalized pustular psoriasis showed higher odds of diabetes mellitus (5.42 [1.56–18.83]) compared with AD. In conclusion, Asian patients with all types of psoriasis should be closely monitored for the development of metabolic and neurologic diseases, especially men and those aged ≥ 40 years.

Abstract There are limited large population-based cohort studies on the risk of incident autoimmune diseases among patients with newly diagnosed psoriatic disease. The objective of this study was to assess the risk of autoimmune diseases in patients with newly diagnosed psoriatic disease. Using the Korean National Health Insurance Service database, patients with newly diagnosed psoriatic disease between 2007 and 2019 were included. Comparators were randomly selected and matched according to age and sex. A total of 321,354 patients with psoriatic disease and 321,354 matched comparators were included in this study. Patients with psoriatic disease had a significantly higher risk of Crohn’s disease [adjusted hazard ratio (aHR), 1.95; 95% confidence interval (CI) 1.42–2.67], ulcerative colitis (aHR, 1.65; 95% CI 1.39–1.96), systemic lupus erythematosus (aHR, 1.86; 95% CI 1.34–2.57), rheumatoid arthritis (aHR, 1.63; 95% CI 1.52–1.76), ankylosing spondylitis (aHR, 2.32; 95% CI 1.95–2.77), alopecia areata (aHR, 1.41; 95% CI 1.35–1.46), and type 1 diabetes (aHR, 1.23; 95% CI 1.11–1.37). However, the risk of Graves’ disease, Hashimoto’s disease, Sjögren’s syndrome, and systemic sclerosis was not significantly different between the groups. In conclusion, patients with newly diagnosed psoriatic disease may have a significantly increased risk of incident autoimmune diseases.

Abstract Background Riehl melanosis, characterized by diffuse brown to grey hyperpigmentation of the face and neck, affects middle‐aged women with dark skin phototypes. Riehl melanosis prevalence has increased in Korea, and a relationship with henna hair dye has been suspected. In this study, we aimed to evaluate clinical features and patch test results of Riehl melanosis patients and analyse them according to age, sex, and hair dye use. Methods We identified patients showing clinical and histopathological manifestations consistent with Riehl melanosis between January 2009 and December 2019 in our medical centre. Results Of 154 patients, 76.5% had positive patch‐test results, and the most common sensitizing agents were nickel, cobalt, and benzyl salicylate. Patients ≥50 years old were more likely to have spotty hyperpigmentation and less likely to have diffuse patterns, while lesions in the younger‐aged group were more commonly accompanied by erythema. Preceding erythema was found more often in female patients. Hair dye usage was more likely to be associated with aggravation of symptoms in females. Patients who developed Riehl melanosis after hair‐dye use more frequently had lesions on the forehead and were diagnosed an average of 14.1 months earlier as compared with other patients. Short disease duration, aggravation by hair dye (except henna), laser therapy, and longer follow‐up periods were related to good treatment responses. Conclusions Detailed history taking regarding disease duration and aggravating factors as well as the length of the period of laser therapy can be important for the management of Riehl melanosis patients.

Abstract Background Distinguishing benign lesion from early malignancy in melanocytic lesions of the nail unit still remains a diagnostic challenge, both clinically and histopathologically. While several immunohistochemistry (IHC) stainings have been suggested to help discriminate benign subungual melanocytic proliferation (SMP) and subungual melanoma in situ (MIS), the diagnostic utility of IHC staining for cyclin D1 and PRAME has not been thoroughly investigated in melanocytic lesions of nail unit. Methods This retrospective study included cases of benign SMP and subungual MIS confirmed by biopsy at Asan Medical Center from January 2016 to December 2020. Cases of melanocytic activation without proliferation and melanoma where dermal invasion was identified were excluded. Cyclin D1 and PRAME expression was assessed by counting proportion of melanocytes with nuclear positivity under 200x magnification. Results A total of 14 patients with benign SMP and 13 patients with subungual MIS were included in this study. 11 patients with benign SMP (71.4%) and 5 patients with subungual MIS (38.5%) showed > 60% nuclear immunostaining for cyclin D1, respectively. While 13 patients with benign SMP (92.9%) showed totally negative staining for PRAME, 10 patients with subungual MIS (76.9%) exhibited > 50% nuclear immunostaining for PRAME. Using the cutoff of 10%, PRAME exhibited good overall discrimination between benign SMP and subungual MIS (AUC = 0.849, 95% CI = 0.659–0.957). Conclusions This study suggests that PRAME IHC staining as a reliable discriminator in distinguishing subungual MIS from benign SMP.

Abstract Cold atmospheric plasma (CAP) has been incorporated into various fields, including promotion of cutaneous wound healing. Atopic dermatitis (AD) is a chronic cutaneous condition characterized by inflammation-induced skin wounds and impaired skin barrier function. To investigate whether CAP may improve AD using an animal model. Dermatophagoides farinae extracts (DFE)-induced murine models of AD were used in this study. The plasma-treated group received a total of 6 CAP treatments during 2 weeks, while the control group did not receive any treatment. Differences in dermatitis severity, transepidermal water loss (TEWL), serum level of immunoglobulin (Ig) E and epidermal thickness were evaluated in both groups. The dermatitis severity was significantly improved by CAP treatment. TEWL was lower in the plasma-treated group compared with the non-treated control group. Serum Ig E dropped significantly after treatment with CAP. Difference in epidermal thickness of the ear skin was not significant between the plasma-treated and non-treated groups. Localized treatment of AD with CAP decreases dermatitis severity, TEWL, and serum Ig E level. These results show CAP’s potentials as a novel therapeutic modality for AD.

Abstract Cold atmospheric plasma generates free radicals through the ionization of air at room temperature. Its effect and safety profile as a treatment modality for atopic dermatitis lesions have not been evaluated prospectively enough. We aimed to investigate the effect and safety of cold atmospheric plasma in patients with atopic dermatitis with a prospective pilot study. Cold atmospheric plasma treatment or sham control treatment were applied respectively in randomly assigned and symmetric skin lesions. Three treatment sessions were performed at weeks 0, 1, and 2. Clinical severity indices were assessed at weeks 0, 1, 2, and 4 after treatment. Additionally, the microbial characteristics of the lesions before and after treatments were analyzed. We included 22 patients with mild to moderate atopic dermatitis presented with symmetric lesions. We found that cold atmospheric plasma can alleviate the clinical severity of atopic dermatitis. Modified atopic dermatitis antecubital severity and eczema area and severity index score were significantly decreased in the treated group. Furthermore, scoring of atopic dermatitis score and pruritic visual analog scales significantly improved. Microbiome analysis revealed significantly reduced proportion of Staphylococcus aureus in the treated group. Cold atmospheric plasma can significantly improve mild and moderate atopic dermatitis without safety issues.

Cold atmospheric plasma (CAP) may have applications in treating various types of malignant tumors. This study assessed the anticancer effects of CAP using melanoma and colon cancer cell lines. CAP treatment significantly reduced the in vitro viability of melanoma and colon cancer cell lines and had a negligible effect on the viability of normal human melanocytes. Additionally, CAP and epidermal growth factor receptor (EGFR) inhibitor had an additive anticancer effect in a CAP-resistant melanoma cell line. Reactive oxygen and nitrogen species known to be generated by CAP enhanced the anticancer effects of CAP and EGFR inhibitors. The in vivo anticancer activities of CAP were evaluated by testing its effects against syngeneic tumors induced in mice by melanoma and colon cancer cells. CAP treatment reduced tumor volume and weight in both cancer models, with the extent of tumor reduction dependent on the duration and number of CAP treatments. Histologic examination also revealed the tumoricidal effects of CAP in both tumor models. In conclusion, CAP inhibits the growth of mouse melanoma and colon cancer cell lines in vitro and shows tumoricidal effects against mouse models of melanoma and colon cancer in vivo.

Primary cribriform carcinoma of the skin is an indolent, rare, adnexal tumor. Although its malignant potential remains uncertain, no recurrence or metastasis has been reported. A 33-year-old man presented with a solitary, erythematous, subcutaneous nodule on the right knee. The clinical impression was epidermal cyst, and the resected tumor demonstrated a well-circumscribed mass in the dermis and subcutis. The tumor was composed of two regions: a solid component and a cribriform component. The solid component (90%) showed multiple solid nests of epithelial cells. Individual cells had large, oval-to-round, hyperchromatic, pleomorphic nuclei with a nuclear groove. The cribriform component (10%) showed similar neoplastic cells with many prominent lumina. Some lumina had an eosinophilic substance that exhibited a positive periodic acid-Schiff reaction. No recurrence or metastasis was observed within a follow-up period of eight months after excision. In conclusion, we report the first case of primary cribriform carcinoma of the skin in Korea.

Background:. Botulinum neurotoxin A (BoNT-A) injection is the most widely performed aesthetic procedure and a first-line therapeutic option for various medical conditions. The potential for BoNT-A immunoresistance and secondary nonresponse related to neutralizing antibody (NAb) formation warrants attention as the range of BoNT-A aesthetic applications continues to expand. Methods:. An international multidisciplinary panel reviewed published evidence on BoNT-A immunoresistance in aesthetic and therapeutic applications and discussed best practices integrating clinical, ethical, and aesthetic considerations. Consensus statements relating to awareness, assessment, and management of the risk of NAb-related secondary nonresponse in aesthetic practice were developed. Results:. There was a consensus that, as doses used in aesthetic practice become like those in therapeutics, rates of NAb formation may be expected to increase. However, the true extent of NAb formation in aesthetics is likely underestimated due to limitations of published evidence and variability in treatment patterns of aesthetic patients. Since BoNT-A therapy is often lifelong, practitioners need to recognize immunogenicity as a potential complication that might affect future therapeutic use and strive to minimize modifiable risk factors. The selection and use of a BoNT-A product with the least immunogenic potential from the beginning may thus be advantageous, especially when treatment with high doses is planned. Conclusions:. In view of current trends in BoNT-A aesthetic use, it is essential for practitioners to conduct thorough clinical assessments, inform patients of treatment risks, and develop BoNT-A treatment plans to minimize immunogenicity. This can help preserve the option of continued or future BoNT-A treatment with satisfactory outcomes.

Background Although deep neural networks have shown promising results in the diagnosis of skin cancer, a prospective evaluation in a real-world setting could confirm these results. This study aimed to evaluate whether an algorithm (http://b2019.modelderm.com) improves the accuracy of nondermatologists in diagnosing skin neoplasms. Methods A total of 285 cases (random series) with skin neoplasms suspected of malignancy by either physicians or patients were recruited in two tertiary care centers located in South Korea. An artificial intelligence (AI) group (144 cases, mean [SD] age, 57.0 [17.7] years; 62 [43.1%] men) was diagnosed via routine examination with photographic review and assistance by the algorithm, whereas the control group (141 cases, mean [SD] age, 61.0 [15.3] years; 52 [36.9%] men) was diagnosed only via routine examination with a photographic review. The accuracy of the nondermatologists before and after the interventions was compared. Results Among the AI group, the accuracy of the first impression (Top-1 accuracy; 58.3%) after the assistance of AI was higher than that before the assistance (46.5%, P = .008). The number of differential diagnoses of the participants increased from 1.9 ± 0.5 to 2.2 ± 0.6 after the assistance (P < .001). In the control group, the difference in the Top-1 accuracy between before and after reviewing photographs was not significant (before, 46.1%; after, 51.8%; P = .19), and the number of differential diagnoses did not significantly increase (before, 2.0 ± 0.4; after, 2.1 ± 0.5; P = .57). Conclusions In real-world settings, AI augmented the diagnostic accuracy of trainee doctors. The limitation of this study is that the algorithm was tested only for Asians recruited from a single region. Additional international randomized controlled trials involving various ethnicities are required.

The progression of androgenetic alopecia is closely related toandrogen-inducible transforming growth factor (TGF)-β1 secretionby hair follicle dermal papilla cells (DPCs) in bald scalp.Physiological levels of androgen exposure were reported toincrease reactive oxygen species (ROS) generation. In thisstudy, rat vibrissae dermal papilla cells (DP-6) transfected withandrogen receptor showed increased ROS production followingandrogen treatment. We confirmed that TGF-β1 secretion isincreased by androgen treatment in DP-6, whereas androgeninducibleTGF-β1 was significantly suppressed by the ROSscavenger,N-acetyl cysteine. Therefore, we suggest that inductionof TGF-β1 by androgen is mediated by ROS in hair follicleDPCs. [BMB Reports 2013; 46(9): 460-464]

A recent study suggested that a cell-free extract of human adipose stem cells (hASCs-E) has beneficial effects on neurological diseases by modulating the host environment. Here, we investigated the effects of hASCs-E in several experimental models of stroke in vitro (oxygen and glucose deprivation, OGD) and in vivo (transient or permanent focal cerebral ischemia and intracerebral hemorrhage, ICH). Ischemia was induced in vitro in Neuro2A cells, and the hASCs-E was applied 24 h before the OGD or concurrently. Focal cerebral ischemia was induced by unilateral intraluminal thread occlusion of the middle cerebral artery (MCA) in rats for 90 min or permanently, or by unilateral MCA microsurgical direct electrocoagulation in mice. The ICH model was induced with an intracerebral injection of collagenase in rats. The hASCs-E was intraperitoneally administered 1 h after the stroke insults. Treatment of the hASCs-E led to a substantially high viability in the lactate dehydrogenase and WST-1 assays in the in vitro ischemic model. The cerebral ischemic and ICH model treated with hASCs-E showed decreased ischemic volume and reduced brain water content and hemorrhage volume. The ICH model treated with hASCs-E exhibited better performance on the modified limb placing test. The expression of many genes related to inflammation, immune response, and cell-death was changed substantially in the ischemic rats or neuronal cells treated with the hASCs-E. These results reveal a neuroprotective role of hASCs-E in animal models of stroke, and suggest the feasible application of stem cell-based, noninvasive therapy for treating stroke.

The dermal papilla cells (DPCs) of hair follicles are known tosecrete paracrine factors for follicular cells. Shotgun proteomicanalysis was performed to compare the expression profiles ofthe secretomes of human DPCs and dermal fibroblasts (DFs).In this study, the proteins secreted by DPCs and matched DFswere analyzed by 1DE/LTQ FTICR MS/MS, semi-quantitativelydetermined using emPAI mole percent values and then characterizedusing protein interaction network analysis. Among the1,271 and 1,188 proteins identified in DFs and DPCs, respectively,1,529 were further analyzed using the IngenuityPathway Analysis tool. We identified 28 DPC-specific extracellularmatrix proteins including transporters (ECM1, A2M),enzymes (LOX, PON2), and peptidases (C3, C1R). The biochemically-validated DPC-specific proteins included thrombospondin1 (THBS1), an insulin-like growth factor binding protein3(IGFBP3), and, of particular interest, an integrin beta1subunit (ITGB1) as a key network core protein. Using the shotgunproteomic technique and network analysis, we selectedITGB1, IGFBP3, and THBS1 as being possible hair-growthmodulating protein biomarkers. [BMB reports 2012; 45(4):253-258]

Tissue pericytes respond to injury, and support vascular and tissue regeneration. The presence of pericytes in the circulation may provide an attractive framework for tissue regeneration. Here, we detected multipotent pericyte-like cells in the circulating blood and determined its profiles during cerebral ischemia. Pericyte-like cells were isolated from the peripheral blood of acute stroke patients or asymptomatic individuals with vascular risk factors by fluorescence or magnetic activated cell sorting with anti-PDGF receptor-beta (PDGFRβ) antibody. The morphologic and molecular features of circulating PDGFRβ+ cells were compared with tissue pericytes, and the associations with respect to quantity in the blood, culture outcome, and patient characteristics were analyzed. We found an increase in circulating PDGFRβ+ cells in acute stroke patients compared to controls and a correlation with neurologic impairment. The isolated PDGFRβ+ cells expressed mesenchymal stem cell markers, proliferated, and were multipotent under permissive culture conditions. The multipotent nature of these cells was comparable to fat-derived PDGFRβ+ cells. These cells could be obtained by pharmacologic stimulation using bone marrow mobilizer. Circulating PDGFRβ+ cells will be useful for future research involving endogenous recovery or autologous cell-based therapy.