NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism.

Ultraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor (MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellular redox changes that affect tyrosinase degradation. These changes regulate melanosome maturation and, consequently, eumelanin levels and pigmentation. Topical application of small-molecule inhibitors yielded skin darkening in human skin, and mice with decreased NNT function displayed increased pigmentation. Additionally, genetic modification of NNT in zebrafish alters melanocytic pigmentation. Analysis of four diverse human cohorts revealed significant associations of skin color, tanning, and sun protection use with various single-nucleotide polymorphisms within NNT. NNT levels were independent of UVB irradiation and redox modulation. Individuals with postinflammatory hyperpigmentation or lentigines displayed decreased skin NNT levels, suggesting an NNT-driven, redox-dependent pigmentation mechanism that can be targeted with NNT-modifying topical drugs for medical and cosmetic purposes.

Spatial transcriptome analysis of amelanotic acral melanoma reveals distant molecular determinants compared to pigmented acral melanoma.

BACKGROUND: Amelanotic acral melanoma (AAM) is a rare type of acral melanoma associated with poor prognosis. OBJECTIVES: We aimed to investigate the transcriptomic differences between AAM and pigmented acral melanoma (PAM). METHODS: The differences in spatially resolved transcriptome profiles of 9 AAM patients with 29 regions of interest (ROIs) and 11 PAM patients with 46 ROIs were investigated using S100b and CD3 morphology markers. RESULTS: In S100b-positive tumor cell areas, we detected 11 upregulated differentially expressed genes (DEGs), including chaperone/ubiquitin-associated DEGs, and 82 downregulated DEGs, including human leukocyte antigen, in AAMs compared with PAMs. Protein-protein interaction network and pathway analyses revealed significant enrichment of dysregulated translational and nonsense-mediated decay pathways but significant decreases in antigen processing and presentation, interferon signaling, and melanin biosynthesis pathways in S100b-positive ROIs of AAMs compared with those of PAMs. In tumor-associated immune cell areas, the numbers of CD8 T cells (p = 0.044) and M1 macrophages (p = 0.014) were significantly decreased, whereas those of monocytes (p = 0.045) and endothelial cells (p = 0.04) were increased in AAMs compared with those in PAMs. CONCLUSIONS: In conclusion, these findings could widen our understanding of the biological differences between AAMs and PAMs that might result in a different clinical course.

Baseline Serum neutrophil-to-lymphocyte ratio in acral melanoma compared with nonacral melanoma and its prognostic significance.

BACKGROUND: Acral lentiginous melanoma (ALM), a cutaneous melanoma subtype, exhibits a poorer prognosis than nonacral cutaneous melanoma (NACM). The neutrophil-to-lymphocyte ratio (NLR) is emerging as a prognostic indicator across diverse cancers. OBJECTIVE: We explored the baseline NLR disparities between ALM and NACM, and the NLR's prognostic significance in patients with ALM. METHODS: We reviewed records of patients with ALM and NACM diagnosed between 1997 and 2022, analyzing medical data. RESULTS: Among 327 and 159 patients with ALM and NACM, respectively, baseline NLR varied based on distinct clinicopathologic factors between ALM and NACM. In stage 3 to 4 melanomas, the median NLR for ALM (2.18; IQR, 1.70-3.08) significantly surpassed NACM (1.74; IQR, 1.33-2.53) (P = .029). In patients with ALM, high NLR (hazard ratio, 1.64; 95% CI, 1.02-2.66; P = .043) was independently correlated with poor progression-free survival when adjusting for ulceration, Breslow thickness of ≥2 mm, and nodal invasion. LIMITATIONS: Single-center, retrospective design. CONCLUSION: Advanced-stage ALM exhibited a significantly higher baseline NLR compared with that of NACM. Evaluating baseline NLR could provide valuable prognostic insights for patients with ALM.

A rare case of secondary cutaneous lymphoplasmacytic lymphoma clinically presenting as acquired cutis laxa.

Lymphoplasmacytic lymphoma (LPL) is a rare variant of non-Hodgkin lymphoma, accounting for <1% of cases. Skin involvement in LPL is quite rare-accounting for approximately 5% of extramedullary disease-and includes a variety of clinical morphologies, such as erythematous-to-violaceous plaques, violaceous nodules or tumors, and ulceration at various anatomical sites. Herein, we report the case of a 45-year-old Korean woman who presented with generalized erythematous indurated plaques and pendulous skin growths, which were asymptomatic, with marked diffuse infiltration of lymphocytes and plasma cells in the dermis. Immunohistochemical studies revealed that the lymphoid cells expressed CD3, CD79a, and cytoplasmic IgG, but lacked CD10 and IgM. Moreover, kappa light chain restriction and monoclonal immunoglobulin heavy chain gene rearrangement were observed. Upon further workup, lymphoma involvement was reported in multiple lymph nodes, including those in the cervical and axillary regions. This case shows a unique form of cutaneous LPL clinically presenting as acquired cutis laxa, emphasizing the dermatologists' need to be vigilant for variant forms of this disease.

Spatial transcriptomic analysis of tumour-immune cell interactions in melanoma arising from congenital melanocytic nevus.

BACKGROUND: Studies on the interaction between tumour-infiltrating immune cells (TIICs) and tumour cells in melanoma arising from congenital melanocytic nevus (CMN) are lacking. OBJECTIVE: The aim of this study was to determine the intratumoral immune landscape of TIICs and tumour cells during invasion and metastasis. METHODS: Tissue specimens were obtained from patients with melanoma originating from CMN. Differential gene expression in melanoma cells and TIICs during invasion and metastasis was determined using spatial transcriptomics. RESULTS: As invasion depth increased, the expression of LGALS3, known to induce tumour-driven immunosuppression, increased in melanoma cells. In T cells, the expression of genes that inhibit T-cell activation increased with increasing invasion depth. In macrophages, the expression of genes related to the anti-inflammatory M2 phenotype was upregulated with increasing invasion depth. Compared to primary tumour cells, melanoma cells in metastatic lesions showed upregulated expression of genes associated with cancer immune evasion, including AXL and EPHA2, which impede T-cell recruitment, and BST2, associated with M2 polarization. Furthermore, T cells showed increased expression of genes related to immunosuppression, and macrophages exhibited increased expression of genes associated with the M2 phenotype. CONCLUSIONS: The interaction between melanomas arising from CMN and TIICs may be important for tumour progression and metastasis.

Morphological characteristics of facial scars: A retrospective analysis according to scar location, onset, age, and cause.

The morphology of facial scars shows a wide variation in terms of texture and colour. To date, there are no reliable predictors of aberrant scarring. We conducted a retrospective analysis to identify factors associated with specific scar features and types. Photographs and medical records of 428 patients with facial scars were retrospectively reviewed. Patients with keloids were excluded. The mean age of the patients was 45.43 ± 23.13 years with a male-to-female ratio of 1:1.36. Atrophic scars were the most common (42.8%), followed by flat scars (38.7%) and hypertrophic scars (18.5%). Scars on the forehead were more likely to be atrophic, whereas scars on the chin/jaw and around the mouth were more likely to be hypertrophic. Hypopigmentation was significantly more common in scars located on the forehead. Redness (erythema) was significantly more common in scars located on the chin/jaw. Old scars were less likely to be erythematous, and hypertrophic. Atrophic scars were more common in younger patients. Scars caused by dermatologic conditions, such as acne, were more likely to be atrophic, whereas surgical scars had the lowest risk of being atrophic or hypertrophic. In conclusion, the location, onset, and cause of facial scars were associated with specific features of scars.

Efficacy of Asymmetric siRNA Targeting Androgen Receptors for the Treatment of Androgenetic Alopecia.

Asymmetric small interfering RNAs (asiRNAs) that mediate RNA interference have been investigated for therapeutic use in various tissues, including skin tissue. Androgenetic alopecia (AGA) is caused by a combination of genetic factors, resulting in sensitivity to dihydrotestosterone (DHT), which binds to the androgen receptor (AR) to mediate a series of biomolecular changes leading to hair loss. This study aimed to evaluate the therapeutic potential of a cell-penetrating, AR-targeting asiRNA (cp-asiAR) for AGA treatment, which was designed to silence the AR gene. AGA mouse models were developed by stimulation with DHT, and ex vivo human scalp tissues were also used for analysis. Cp-asiAR-mediated changes in mRNA expression and protein levels of AR were assessed along with the examination of phenotypic improvements in mouse model of AGA. We also assessed downstream signaling associated with AR in primary human dermal papilla (DP) cells. Several cp-asiARs were screened for selecting the optimal sequence of AR using cell lines in vitro. A cholesterol-conjugated, chemically modified cp-asiAR candidate was optimized under passive uptake conditions in vitro. Intradermal cp-asiAR injection efficiently reduced mRNA and protein levels corresponding to AR in mouse models. Moreover, cp-asiAR injection promoted hair growth in mouse models with DHT-induced AGA. In ex vivo human hair follicle culture, the proportion of telogen hair decreased, and the mean hair bulb diameter increased in the cp-asiAR-treated group. In isolated primary human DP cells, AR expression was effectively downregulated by cp-asiAR. Furthermore, cp-asiAR attenuated DHT-mediated increases in interleukin-6, transforming growth factor-ß1, and dickkopf-1 levels. No significant toxicity was observed in DP cells after cp-asiAR treatment. Cp-asiAR treatment showed effective downregulation of AR expression and prevention of DHT-mediated alterations in the hair cycle and hair diameter, indicating its potential as a novel therapeutic option for AGA.

Real-time, in vivo skin cancer triage by laser-induced plasma spectroscopy combined with a deep learning-based diagnostic algorithm.

BACKGROUND: Although various skin cancer detection devices have been proposed, most of them are not used owing to their insufficient diagnostic accuracies. Laser-induced plasma spectroscopy (LIPS) can noninvasively extract biochemical information of skin lesions using an ultrashort pulsed laser. OBJECTIVE: To investigate the diagnostic accuracy and safety of real-time noninvasive in vivo skin cancer diagnostics utilizing nondiscrete molecular LIPS combined with a deep neural network (DNN)-based diagnostic algorithm. METHODS: In vivo LIPS spectra were acquired from 296 skin cancers (186 basal cell carcinomas, 96 squamous cell carcinomas, and 14 melanomas) and 316 benign lesions in a multisite clinical study. The diagnostic performance was validated using 10-fold cross-validations. RESULTS: The sensitivity and specificity for differentiating skin cancers from benign lesions using LIPS and the DNN-based algorithm were 94.6% (95% CI: 92.0%-97.2%) and 88.9% (95% CI: 85.5%-92.4%), respectively. No adverse events, including macroscopic or microscopic visible marks or pigmentation due to laser irradiation, were observed. LIMITATIONS: The diagnostic performance was evaluated using a limited data set. More extensive clinical studies are needed to validate these results. CONCLUSIONS: This LIPS system with a DNN-based diagnostic algorithm is a promising tool to distinguish skin cancers from benign lesions with high diagnostic accuracy in real clinical settings.

Clinicopathologic Characteristics of Trauma-Related Nail Apparatus Melanoma: A Comparative Study according to the Presence of Trauma prior to Melanoma Development.

BACKGROUND: Nail apparatus melanoma (NAM) is a subtype of cutaneous melanoma occurring at nail units and belongs to the acral lentiginous melanoma subgroup. Due to its unique anatomical structure to protect the acral site, mechanical trauma may have a clinicoprognostic impact on NAM. Therefore, we investigated the clinicoprognostic and histopathological characteristics of NAM according to the presence of trauma history prior to melanoma development. METHODS: Clinicopathological and follow-up data of patients with NAM according to trauma history were obtained. RESULTS: We included 87 patients with NAM, 21.8% of whom had a previous trauma history. Trauma-related NAMs were more likely to involve the toenail (p = 0.040), include a high proportion of amelanotic melanomas (p = 0.038) as well as nail bed tumor (p = 0.013), and have a longer time interval between the onset of nail change and confirmed diagnosis (p = 0.012). Moreover, survival analysis revealed that trauma-related NAMs more frequently showed progression in general (p = 0.034) and nodal metastasis (p = 0.047) and had worse prognosis in terms of progression-free survival (p = 0.004). CONCLUSION: In conclusion, NAMs with previous trauma have unique clinicoprognostic characteristics. The specific clinicopathological features of NAMs according to trauma indicate that trauma may play a role in melanoma development.

Clinicoprognostic Study of Hydroa Vacciniforme-like Lymphoproliferative Diseases: A Systematic Review.

BACKGROUND: Limited clinicopathological and prognostic data are available on hydroa vacciniforme (HV)-like lymphoproliferative diseases (HVLPD). METHODS: This systematic review searched HVLPD reports in Medline via PubMed, Embase, Cochrane, and CINAHL databases in October 2020. RESULTS: A total of 393 patients (65 classic HV, 328 severe HV/HV-like T-cell lymphoma [HVLL]) were analyzed. Among severe HV/HVLL cases, 56.0% were Asians, whereas 3.1% were Caucasians. Facial edema, hypersensitivity to mosquito bites, the onset of skin lesion, and percentage of severe HV/HVLL differed significantly by race. Progression to systemic lymphoma was confirmed in 9.4% of HVLPD patients. Death occurred in 39.7% patients with severe HV/HVLL. Facial edema was the only risk factor associated with progression and overall survival. Mortality risk was higher in Latin Americans than in Asians and Caucasians. CD4/CD8 double-negativity was significantly associated with the worst prognosis and increased mortality. CONCLUSION: HVLPD is a heterogeneous entity with variable clinicopathological features associated with genetic predispositions.

Performance of PRAME immunohistochemistry compared with that of c-Kit, c-Myc, or cyclin D1 for the diagnosis of acral melanocytic tumors.

The diagnostic role of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has not been thoroughly evaluated for acral melanocytic tumors. The objective of this study was to evaluate the utility of this modality for the diagnosis of acral melanocytic tumors compared with other potential markers. Melanocytic tumors were classified as either acral nevi, challenging melanocytic tumors (superficial atypical melanocytic proliferation of uncertain significance (SAMPUS)-favor benign (SAMPUS-FB), SAMPUS-favor malignant (SAMPUS-FM)) or acral melanomas. A total of 106 acral melanocytic tumors including acral nevi (n = 32), SAMPUS-FB (n = 17), SAMPUS-FM (n = 20), and acral melanomas (n = 37) were included. Diagnostic power, assessed using an area under the receiver operating characteristic curve (AUC) for distinguishing acral melanomas and acral nevi, was highest for PRAME (AUC = 0.997), followed by c-Myc (AUC = 0.755), cyclin D1 (AUC = 0.652), and c-Kit (AUC = 0.573). At a PRAME expression level ≥30% as a positive test for acral melanoma, the sensitivity and specificity of this marker for discriminating acral melanoma from acral nevus were 100% and 96.9%, respectively. PRAME immunohistochemistry also discriminated SAMPUS-FM from SAMPUS-FB with a sensitivity and specificity of 90.0% and 76.5%, respectively. In conclusion, PRAME immunohistochemistry can be used effectively to distinguish between various spectra of acral melanocytic neoplasms.

Anticancer Effect of Cold Atmospheric Plasma in Syngeneic Mouse Models of Melanoma and Colon Cancer.

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.

Clinicoprognostic implications of head and neck involvement by mycosis fungoides: A retrospective cohort study.

BACKGROUND: The clinicoprognostic implications of head and neck involvement of mycosis fungoides (MF) are poorly understood. OBJECTIVES: To evaluate the association of head and neck involvement on the clinicoprognostic features of MF. METHODS: The clinical features and survival outcomes of patients with MF in a Korean academic medical center database were retrospectively evaluated according to the presence of head and neck involvement at diagnosis. FINDINGS: Cases of MF with (group A, n = 39) and without (group B, n = 85) head and neck involvement at diagnosis were identified. Advanced-stage disease (stages IIB-IVB) was more common in group A (43.6%) than in group B (5.9%) (P < .001). MF progression, extracutaneous dissemination, and large-cell transformation more commonly occurred in group A than in group B. The 10-year overall survival rate was worse in group A (53.4%) compared with group B (81.6%) (P < .001). Head and neck involvement at diagnosis was associated with poor prognosis in early-stage MF (stages IA-IIA) and was independently associated with worse progression-free survival (hazard ratio, 24.4; 95% confidence interval, 2.2-267.6; P = .009). LIMITATIONS: A single center, retrospective design. CONCLUSION: Head and neck involvement of MF was associated with a poor prognosis.

A randomized, double-blind, multi-center, placebo-controlled, Phase 2 clinical trial to evaluate the efficacy and safety of DWJ211 in the treatment of moderate to severe submental fat.

Excessive accumulation of submental fat (SMF) causes a lower face cosmetic problem. A lipolytic injectable has recently been developed as a solution. The objective of this study is to investigate the effects and safety of DWJ211 (a newly developed lipolytic injectable) in the reduction of SMF and to identify the optimum dose. In this multi-center, double-blind, placebo-controlled study, subjects with moderate to severe SMF were randomized to injections of DWJ211 0.5%, DWJ211 1%, DWJ211 2% or placebo in the submental area, every 4 weeks, up to Week 12. Efficacy was determined by improvements in physician-assisted SMF rating scales (PA-SMFRS) and subject-assisted SMF rating scales (SA-SMFRS) 4 weeks after the last treatment (Week 16). Safety was assessed by inquiries, subject diary entries of adverse events, laboratory tests, and vital sign checks. Of 140 enrolled subjects, 136 were included in the analysis. The proportions of subjects, who achieved ≥1-grade improvement on the PA-SMFRS were 41.7%, 65.7%, 84.4%, and 72.7%, and the proportions of subjects, who achieved ≥1-grade improvement on the SA-SMFRS were 50.0%, 71.4%, 93.8%, and 81.8% for the placebo, DWJ211 0.5%, DWJ211 1%, and DWJ211 2% group, respectively. Adverse drug reactions (ADRs) were more common in each of the treatment groups compared with placebo, with the most common ADR being injection site pain. No subjects experienced any serious adverse events. In conclusion, the 1% DWJ211 dose was beneficial for SMF reduction and had a tolerable safety profile. Thus, we selected 1% as the dose to be tested in a Phase 3 clinical trial.

Clinical implications of facial psoriasis in children and adolescents.

BACKGROUND/OBJECTIVES: The clinical implications of facial involvement in pediatric patients with psoriasis have not been adequately studied. The objectives of this study are to evaluate the association between facial involvement and clinical features including disease severity of psoriasis in children and adolescents. METHODS: The clinical features of patients aged below 20 years diagnosed with psoriasis were retrospectively evaluated and grouped based on the presence or absence of facial involvement at presentation. Demographic and clinical data were compared between groups. RESULTS: Of the 175 patients, 110 patients (62.9%) had facial involvement of psoriasis at presentation. The group with facial involvement was significantly younger at disease onset (p = .032) and had a higher body mass index (BMI) (p = .043) and psoriasis area and severity index (PASI) score (p <.001). The severity of pruritus was significantly higher in the facial than in the non-facial group (p = .020). Involvement of the nose was associated with the highest disease severity as assessed by the PASI score and affected body surface area. A significantly higher number of treatment modalities were used in the facial group than in the non-facial group (p = .013). The BMI (odds ratio (OR), 1.39; 95% CI (confidence interval), 1.07-1.80) and PASI score (OR, 1.45; 95% CI, 1.03-2.03) were independent factors associated with facial involvement of psoriasis. CONCLUSIONS: Facial involvement in psoriasis was associated with higher disease severity and more treatment modalities in children and adolescents.

Clinical and histopathological analysis of 141 dermatofibrosarcoma protuberans in Korea: A comparative study according to trauma.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare fibrohistiocytic tumour of unknown pathogenesis with intermediate malignant potential. Although trauma has been hypothesized as a predisposing factor for DFSP development, clinicopathological characteristics of trauma-related DFSP have not been investigated. OBJECTIVE: This study investigated the differences between trauma-associated DFSP and trauma-unrelated DFSP. METHODS: Patients histopathologically diagnosed with DFSP from January 2000 to December 2019 at the Dermatology Department were included. Clinical, histopathological, prognostic features and trauma history were analysed. RESULTS: We recruited 141 patients with DFSP (mean age, 36.1 years; male: female, 1:1.01). Recurrence and systemic metastasis were observed in 15.6% and 2.8% of patients, respectively. Older patients were likely to develop DFSP at the trauma sites more frequently on the face and lower legs. The active-growing lesions were more frequently associated with trauma-related DFSP. Multivariable logistic regression revealed that age at diagnosis (OR: 1.031; 95% CI: 1.004-1.059; p = 0.024) and tumour growth (OR: 3.336; 95% CI: 1.162-9.578, p = 0.025) were significantly associated with trauma-related DFSPs. CONCLUSIONS: The age at diagnosis, lesion location and tumour growth were associated with DFSPs in this study. Analysis of DFSP with trauma history provides a deeper understanding of long-term trauma effects on sarcoma development.

Efficacy and safety of a novel combined 1060-nm and 635-nm laser device for non-invasive reduction of abdominal and submental fat.

The aim of this study was to evaluate the safety and efficacy of combined 1060-nm diode laser and 635-nm low-level laser therapy (LLLT) device for non-invasive reduction of the abdominal and submental fat. Forty-two healthy subjects received single laser treatment on both the abdomen and submental area. Ultrasound images measuring the thickness of abdominal and submental fat were taken at baseline, follow-up at 4, 8, and 12 weeks after treatment. Waist circumference and body weight were also measured at all visits. Adverse events were recorded at all visits. Subjects completed a satisfaction questionnaire at the end of the trial. Twelve weeks after a single treatment with the investigational device, ultrasound images showed statistically significant (P < 0.0001) reductions in abdominal and submental fat by 18.62 and 26.4%, respectively. In addition, significant (P < 0.0001) reduction in waist circumference was observed. Ninety-six percent of subjects rated that they were satisfied. Noted side effects were transient mild to moderate tenderness which subsided within 1 to 3 weeks. No serious treatment-related adverse events were reported. The dual wavelength device combining 1060-nm diode laser with 635-nm LLLT was safe and effective for non-invasive reduction of both abdominal and submental fat.

The efficacy and safety of a fractional microneedle radiofrequency device for the treatment of axillary hyperhidrosis: clinical prospective pilot study.

We aimed to evaluate the efficacy and safety of a fractional microneedle radiofrequency device (FMRD) for the treatment of primary axillary hyperhidrosis (PAH). The FMRD adopted insulated microneedles, which could be located at a depth of up to 4.5 mm and deliver a radiofrequency current in a fractional manner. Also, the device could automatically regulate the amount of the delivered energy. Sixteen Korean patients with PAH received two FMRD treatment sessions at a 3-week interval and were followed-up until week 15. The primary outcome was Patient Satisfaction Scale (PSS) score at each visit. Hyperhidrosis Disease Severity Scale (HDSS) and Global Aesthetic Improvement Scale (GAIS) were also assessed. The area and amount of sweat produced were evaluated by specific tests. Mean PSS score significantly improved from 1.6 at week 3 to 2.5 at week 15 by 56%. More than a 50% improvement in sweating assessed by the PSS score was seen in 63% and 50% of patients at weeks 11 and 15, respectively. Mean HDSS score significantly decreased by week 3 and further decreased by week 7. Mean GAIS scores improved from the first follow-up visit at week 3 and improved again at week 7. The mean hyperhidrosis area assessed by starch-iodine test significantly decreased by 36% at week 15 compared with baseline. Mean transepidermal water loss level significantly decreased by 42% at week 15 compared with baseline. No patients experienced any serious adverse events. FMRD can be an effective and safe treatment modality for PAH.

PD-1 and PD-L1 expression in Kaposi sarcoma: A comparative study according to the pathological stage and clinical characteristics.

BACKGROUND: Kaposi sarcoma (KS) is a mesenchymal tumor with distinct histopathological features according to stage of progression. Programmed death-1 (PD-1) and its ligand PD-L1 play major roles in the immune escape strategy of tumors. OBJECTIVES: This study evaluated expression of PD-1 and PD-L1 in various stages of KS and investigated associations between their expression and clinical characteristics. METHODS: Fifty cases with histopathologically diagnosed KS were classified as early or late stage. These specimens were stained with anti-PD-1 and anti-PD-L1 antibodies. The extent of expression in the intratumoral and peritumoral areas was judged by two dermatopathologists. RESULTS: PD-1 and PD-L1 were expressed in 72.2% (13/18) and 11.1% (2/18) of early-stage cases, respectively, compared with 43.8% (14/32) and 28.1% (9/32) of late-stage cases, respectively. At the late stage, PD-1 expression was significantly higher in the peritumoral area than in the intratumoral area (P = 0.001). PD-1 expression in the intratumoral area was significantly higher at the early stage than at the late stage (P = 0.013). PD-L1 expression in the peritumoral area was significantly higher at the late stage than at the early stage (P = 0.038). CONCLUSIONS: The pattern of PD-1 and PD-L1 expression differs according to the stage of KS, but is unaffected by clinical variables.

A multicenter, randomized, double-blind comparison of two hyaluronic acid fillers in mid-face volume restoration in Asians: A 2-year extension study.

The long-term effectiveness and safety of hyaluronic acid fillers in mid-face volume restoration in Asians remain unclear. The objective of this study was to compare the long-term effectiveness and safety of Neuramis Volume Lidocaine (SHAPE-NVL) and Juvederm Voluma with Lidocaine (VYC-20L) in mid-face volume restoration in Asians. Overall, 88 Korean subjects with moderate-to-severe age-related mid-face volume deficit on the Mid-Face Volume Deficit Scale (MFVDS) received SHAPE-NVL on one side and VYC-20L on the contralateral side of the face. Of the 81 subjects who completed the 48-week primary study, 69 subjects were enrolled in an extension study lasting 104 weeks. MFVDS score and global aesthetic improvement were assessed at each visit. Response was defined as a ≥1-point reduction in MFVDS. At weeks 36 and 48, the responder rates for SHAPE-NVL were 81.93% and 80.72%, while those for VYC-20L were 85.54% and 81.92%, respectively. At the 104-week visit, the responder rates were 73.91% and 72.46% for SHAPE-NVL and VYC-20L, respectively. No subjects experienced any serious adverse events during the trial. SHAPE-NVL and VYC-20L showed comparable longevity and safety in mid-face volume restoration over 2 years in Asians. Both had durable effects for up to 2 years with minimal safety concerns.