Mohs Micrographic Surgery With Digital Pathology Improves Surgical Quality and Efficiency: A Retrospective Cohort Study.

BACKGROUND: Mohs micrographic surgery, involving pathology of the surgical margin, has the lowest recurrence rate for skin cancer. Moreover, because of technological advances, digital pathology systems are gradually being adopted in hospitals. Yongin Severance Hospital was the first hospital to construct a fully digitalized pathology system in Korea. OBJECTIVE: To evaluate the efficiency and characteristics of the digital pathology system for Mohs micrographic surgery. METHODS: The medical records of 80 patients with skin cancer who underwent Mohs micrographic surgery from March 2020 to August 2022 were analyzed for the number of frozen margins, number of stages, operation time, and recurrence rate to compare cases based on the pathology system. RESULTS: Overall, 23 and 57 patients were examined using the conventional and digital pathology systems, respectively. The mean number of final stages was 0.494 lower ( p -value = .008), the time from the previous to the next stage was 0.687-fold shorter ( p = .002), and the rate of switching from positive to negative margins was 1.990 times higher ( p = .044) in the digital than the conventional group. LIMITATIONS: Retrospective single-center experience; short follow-up time. CONCLUSION: Digital pathology reduces operative time and increases accuracy in Mohs micrographic surgery.

A Novel Method of Steroid Delivery to Improve the Efficacy of Intralesional Injection in Keloid Treatment.

BACKGROUND: Keloids are a chronic disease and cause pain, pruritus, and limitation of motion. Intralesional corticosteroid injection is the first-line treatment, but its effects can be limited, even with repeated injections. OBJECTIVE: To investigate the efficacy and safety of a tunneling method of corticosteroid injection compared with conventional intralesional injection. MATERIALS AND METHODS: A retrospective review was conducted of keloid patients treated with intralesional corticosteroid injection by conventional and tunneling methods. RESULTS: A total of 119 cases of keloid were included in the study. Among 78 patients treated with 20 mg/mL triamcinolone, the Investigators' Global Assessment effectiveness score and Observer Scar Assessment Scale (OSAS) score were significantly higher in the tunneling group than the conventional group at 1 month. At 6 months, the tunneling group showed significantly higher effectiveness in the OSAS score than the conventional group. In the tunneling group, the interval between treatments was significantly longer than in the conventional group. The occurrence of side effects was lower in the tunneling method group than in the conventional method group. CONCLUSION: This study reveals the benefits of the tunneling method over the conventional method for therapeutic effect and side effects in keloid treatment.

Male sex and Breslow thickness are important risk factors for recurrence of localized melanoma in Korean populations.

BACKGROUND: Predicting the recurrence of localized melanoma is important; however, studies investigating risk factors for recurrence of localized melanoma are lacking in Asian populations. OBJECTIVE: To identify risk factors for recurrence of localized melanoma in Korean patients. METHODS: We retrospectively reviewed patients with cutaneous melanoma without evidence of metastasis from 2000 to 2017. Logistic and Cox regression analyses were conducted for recurrence. The average follow-up time was 46.2 months. RESULTS: We reviewed the data of 340 patients diagnosed with cutaneous melanoma and staged as melanoma in situ, stages I and II. Acral melanoma (70.3%, 239/340) was the predominant subtype. Ninety-two patients (27.1%) had a recurrence after primary melanoma removal (29 local recurrences, 49 regional metastases, and 28 distant metastases). Some patients had multiple types of recurrence at the same time. Male sex (P = .030) and Breslow thickness greater than 1 mm (P = .008) correlated with an increased risk of recurrence. Breslow thickness greater than 2.5 mm in males and greater than 4 mm in females showed a higher predictive value for recurrence than traditional stages IIB and IIC (hazard ratio 3.743 vs 2.972). LIMITATIONS: This was a single-center retrospective study. CONCLUSION: In patients with localized cutaneous melanoma, male sex and Breslow thickness are the most important prognostic factors for recurrence in Korean populations. Different cutoff values of Breslow thickness may better predict recurrence according to sex.

Successful Treatment of Riehl's Melanosis With Mid-Fluence Q-Switched Nd:YAG 1064-nm Laser.

BACKGROUND AND OBJECTIVES: Riehl's melanosis is a chronic acquired hyperpigmentation disorder that causes significant cosmetic problems for patients with this condition. Several treatment options, including low-fluence Q-switched Nd:YAG (QSNY) 1064-nm laser treatment, have been attempted with inconsistent results. We aimed to investigate the beneficial effect of mid-fluence QSNY 1064-nm laser in the treatment of Riehl's melanosis. STUDY DESIGN/MATERIALS AND METHODS: A retrospective review was conducted on patients repetitively treated with mid-fluence (3.5-5 J/cm2 with a spot size of 5 mm and a pulse rate of 10 Hz) QSNY 1064-nm laser. Twenty-one patients with Riehl's melanosis were involved. Clinical photographs, treatment parameters, and side effects were reviewed to assess the safety and efficacy of the modality. RESULTS: The mean age of the patients was 57.00 ±8.2 years, and there were 20 female patients and 1 male patient. The mean number of treatment sessions was 5.95 ± 3.6, and the mean interval between each session was 39.12 ± 13.4 days. After treatment, the mean melasma area and severity index score decreased from 12.53 ± 10.2 to 5.98 ± 5.3. At the final visit, 16 of the 21 (76.1%) patients were considered to have moderately or very much improved. No severe side effects were observed. CONCLUSIONS: Repetitive mid-fluence QSNY 1064-nm laser treatment may be an effective and safe optional modality for Riehl's melanosis. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Comparison of treatment options for small to medium congenital melanocytic nevi: A retrospective review of 119 cases.

OBJECTIVES: For small to medium sized congenital melanocytic nevi (CMN), the treatment of choice is staged surgical excision. Ablative lasers or pigment-specific lasers have also been recommended for lesions difficult for surgical removal or to avoid surgery. In this study, we retrospectively analyzed the results of several treatment options for CMN to find out the optimal treatment method. METHODS: Patients with small to medium sized CMN were retrospectively reviewed. Treatment options were categorized into four groups: (i) Excision only; (ii) Excision followed by scar laser; (iii) Excision followed by pigment-specific laser; and (iv) Laser only. Treatment response was assessed by investigator's global assessment (IGA) score on a seven-point scale. RESULTS: A total of 119 cases were included. Lesions were most commonly located on the face (59/119, 49.6%), measured 2 ∼ 10 cm in size (72/119, 60.5%), and treated with excision only (50/119, 42.0%). Among treatment options, excision followed by scar laser showed the highest IGA score of 6.38. Options including surgical methods showed higher IGA scores compared to laser-only treatment (P < 0.01). Staged excisions and single excisions showed no difference in IGA scores. Patient satisfaction scores increased after scar laser treatment of the staged excision scar. CONCLUSIONS: For the treatment of small to medium sized CMN, treatment strategies including surgical methods are cosmetically superior to laser-only treatment. Also, the combination of surgical excision with scar laser has the potential for better clinical outcomes and patient satisfaction. Lasers Surg. Med. 51:62-67, 2019. © 2018 Wiley Periodicals, Inc.

Analysis of Risk Factors to Predict Occurrence and Prognosis of Postsurgical Hypertrophic Scar Development: A Review of 4238 Cases.

PURPOSE: This study aimed to identify the risk factors associated with the occurrence and prognosis of hypertrophic scarring following thyroidectomy. MATERIALS AND METHODS: A total of 4238 patients who underwent thyroidectomy were included in this study. A multivariable logistic regression model was developed to identify the risk factors for hypertrophic scar development and its prognosis. RESULTS: Our analysis revealed that hypertrophic scar development was associated with younger age [odds ratio (OR)=0.949, p<0.0001], male sex (OR=0.562, p<0.0001), higher body mass index (OR=1.137, p<0.0001), prominent sternocleidomastoid muscles (OR=2.522, p<0.0001), scarring located within 1 cm of the sternal notch (OR=4.345, p<0.0001), and a history of keloid development (OR=2.789, p=0.0031). Additionally, scar location within 1 cm of the sternal notch (beta=4.326, p=0.0429) and a history of keloid development (beta=23.082, p<0.0001) were found to be associated with the prognosis of hypertrophic scarring. CONCLUSION: The findings of this study provide valuable insights into the risk factors associated with hypertrophic scarring following thyroidectomy. Clinicians can use this information to predict the occurrence of hypertrophic scarring and its prognosis, and take preventative measures accordingly.

Microenvironmental network of clonal CXCL13+CD4+ T cells and Tregs in pemphigus chronic blisters.

BACKGROUNDPemphigus, a rare autoimmune bullous disease mediated by antidesmoglein autoantibodies, can be controlled with systemic medication like rituximab and high-dose systemic corticosteroids combined with immunosuppressants. However, some patients continue to experience chronically recurrent blisters in a specific area and require long-term maintenance systemic therapy.METHODSSkin with chronic blisters was obtained from patients with pemphigus. Immunologic properties of the skin were analyzed by immunofluorescence staining, bulk and single-cell RNA and TCR sequencing, and a highly multiplex imaging technique known as CO-Detection by indEXing (CODEX). Functional analyses were performed by flow cytometry and bulk RNA-Seq using peripheral blood from healthy donors. Intralesional corticosteroid was injected into patient skin, and changes in chronically recurrent blisters were observed.RESULTSWe demonstrated the presence of skin tertiary lymphoid structures (TLSs) with desmoglein-specific B cells in chronic blisters from patients with pemphigus. In the skin TLSs, CD4+ T cells predominantly produced CXCL13. These clonally expanded CXCL13+CD4+ T cells exhibited features of activated Th1-like cells and downregulated genes associated with T cell receptor-mediated signaling. Tregs are in direct contact with CXCL13+CD4+ memory T cells and increased CXCL13 production of CD4+ T cells through IL-2 consumption and TGF-ß stimulation. Finally, intralesional corticosteroid injection improved chronic blisters and reduced skin TLSs in patients with pemphigus.CONCLUSIONThrough this study we conclude that skin TLSs are associated with the persistence of chronically recurrent blisters in patients with pemphigus, and the microenvironmental network involving CXCL13+CD4+ T cells and Tregs within these structures plays an important role in CXCL13 production.TRIAL REGISTRATIONClinicalTrials.gov NCT04509570.FUNDINGThis work was supported by National Research Foundation of South Korea (NRF-2021R1C1C1007179) and Korea Drug Development Fund, which is funded by Ministry of Science and ICT; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare (grant RS-2022-00165917).

Geranyl derivative of phloroacetophenone induces cancer cell-specific apoptosis through Bax-mediated mitochondrial pathway in MCF-7 human breast cancer cells.

Plant-derived polyhenols inhibit cancer cell proliferation and induce apoptosis. Recently, prenylflavonoids and alkyl-phloroacetophenones have been reported for their in vitro antitumor activity. In the present study, we examined the cytotoxic activity of prenyl (3-PAP) and geranyl (3-GAP) derivatives of phloroacetophenone, and xanthohumol (XN), a prenyl-chalcone, in human breast cancer (MCF-7) and human sarcoma (HT1080) cell lines in vitro. 3-GAP showed the strongest cytotoxicity in these cell lines with IC(50) values of less than 10 µM. In addition, we report that 3-GAP is a more potent anti-cancer agent for breast cancer than XN which is a well-known anticancer flavonoid. Moreover, 3-GAP did not induce cytotoxicity in the normal cell line, TCMK-1, whereas 3-PAP and XN significantly reduced TCMK-1 cell viability. In 3-GAP-treated MCF-7 cells, nuclear accumulation and transcriptional activity of p53 were increased. In addition, pro-apoptotic Bax but not B-cell lymphoma 2 (Bcl-2) expression was increased by 3-GAP. In accordance with the Bax increase, 3-GAP induced mitochondrial cytochrome c release and activated caspase-9, an initiator of the caspase cascade. In the MCF-7 cell line which does not express caspase-3, activation of caspase-7, a member of the caspase-3 subfamily, was increased by 3-GAP. The present results indicate that synthetic 3-GAP is a safe and effective anti-cancer agent, and the Bax-mediated mitochondrial pathway is the main apoptosis signaling pathway of 3-GAP in MCF-7 cells.

PTEN Promoter Hypermethylation Is Associated with Breslow Thickness in Acral Melanoma on the Heel, Forefoot, and Hallux.

BACKGROUND: Acral melanoma occurs on glabrous skin or the nail apparatus and is distinct from ultraviolet-related melanoma due to differing genetic alteration patterns. Although the pathogenesis of acral melanoma is not well understood, mechanical stress is thought to induce acral melanoma. The incidence of gene mutation and promoter methylation has been reported in tumors from acral melanoma; however, an association between genetic/epigenetic alterations and mechanical stress in acral melanoma remains unclear. OBJECTIVE: To investigate the relationship between clinical/genetic factors and mechanical stress in acral melanoma. METHODS: A retrospective review of 52 patients diagnosed with acral melanoma was performed. We reviewed the clinical characteristics of patients, tumor status, and tumor location. Mutations in BRAF, NRAS, and the TERT promoter, along with KIT amplification and PTEN promoter methylation were analyzed in the tumors. RESULTS: The heel (34/52, 65.4%) was the most common anatomical tumor site. Mutations in BRAF (6/48, 12.5%), NRAS (6/49, 12.2%), and the TERT promoter (4/33, 12.1%), along with KIT amplification (3/37, 8.1%) and PTEN promoter hypermethylation (12/48, 25.0%) were observed in the tumors. On the forefoot, heel, and hallux, PTEN promoter hypermethylation was significantly associated with Breslow thickness (p=0.001) and ulceration rate (p=0.042). On the midfoot and lesser toes, there was no significant difference in Breslow thickness or ulceration rate regardless of PTEN promoter hypermethylation (p>0.05). CONCLUSION: PTEN promoter hypermethylation is associated with Breslow thickness and tumor ulceration on the forefoot, heel, and hallux in acral melanoma in Korean patients.

Inhibitory effects of clotrimazole on TNF-alpha-induced adhesion molecule expression and angiogenesis.

Cell adhesion molecules play a pivotal role in chronic inflammation and pathological angiogenesis. In the present study, we investigated the inhibitory effects of clotrimazole (CLT) on tumor necrosis factor (TNF)-alpha-induced changes in adhesion molecule expression. CLT dose-dependently inhibited monocyte chemoattractant protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) expressions in TNF-alpha-stimulated HT29 colonic epithelial cells. This inhibitory action of CLT correlated with a significant reduction in TNF-alpha-induced adhesion of monocytes to HT29 cells, which was comparable to the inhibitory effects of anti-ICAM-1 and VCAM-1 monoclonal antibodies on monocyte-epithelial adhesion. These inhibitory actions of CLT were, at least in part, attributable to the inhibition of redox sensitive NF-kappaB activation, as CLT inhibited TNF-alpha-induced ROS generation as well as NF-kappaB nuclear translocation and activation in HT29 cells. Furthermore, the inhibition of TNF-alpha-induced monocyte adhesion was also mimicked by the specific NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC). Inflammatory mediators including TNF-alpha have known to promote angiogenesis, which in turn further contributes to inflammatory pathology. Therefore, we additionally evaluated whether CLT modulates TNF-alpha-induced angiogenesis using in vivo chick chorioallantoic membrane (CAM) assay. The CAM assay showed that CLT dose-dependently attenuated TNF-alpha-induced angiogenesis, and the effect was correlated with decreased inflammation of the CAM tissue. In conclusion, our results suggest that CLT can inhibit TNF-alpha-triggered expression of adhesion molecules, ICAM-1 and VCAM-1, and angiogenesis during inflammation.

Development of Eco-Friendly Polymer Foam Using Overcoat Technology of Deodorant.

Development of eco-friendly polymer foams is an urgent research topic because of the serious environmental pollution caused by trash heaps and the time-release of harmful gases. Polymer PVC foam using azodicarbonamide as a chemical foaming agent has been highly requested for further improvement due to the residual ammonia gas that continuously leaks out. Here, we demonstrate an effective and costless process for the reduction of releasing ammonia from PVC foams using the overcoat technology of deodorants. We have selected four candidate materials, gelite, zeolite, terra alba, and fumed silica as original materials for the deodorant of ammonia, and they showed an ammonia deodorization rate (ADR) of over 80% without any treatment except the fumed silica. When we over-coated the UV-curing agent mixed deodorants on the PVC foams (thickness ~300 µm), the ADR of the terra alba and zeolite complex foams was remarkably higher than 90%, however, the specific gravity and chromaticity were not changed within 20%. This indicates that our developed process using deodorant layer for ammonia reduction has a high potential for the production of eco-friendly polymer foams.

Highly sensitive and novel point-of-care system, aQcare Chlamydia TRF kit for detecting Chlamydia trachomatis by using europium (Eu) (III) chelated nanoparticles.

BACKGROUND: The bacterium Chlamydia trachomatis is one of the leading causes of sexually transmitted diseases worldwide. Since no simple and effective tool exists to diagnose C. trachomatis infections, we evaluated a novel point-of-care (POC) test, aQcare Chlamydia TRF kit, which uses europium-chelated nanoparticles and a time-resolved fluorescence reader. METHODS: The test performance was evaluated by comparing the results obtained using the novel POC testing kit with those obtained using a nucleic acid amplification test (NAAT), using 114 NAAT-positive and 327 NAAT-negative samples. RESULTS: The cut-off value of the novel test was 20.8 with a detection limit of 0.27 ng/mL. No interference or cross-reactivity was observed. Diagnostic accuracy showed an overall sensitivity of 93.0% (106/114), specificity of 96.3% (315/327), positive predictive value (PPV) of 89.8% (106/118), and negative predictive value (NPV) of 97.5% (315/323). The sensitivity of the novel test was much higher than that of currently available POC tests. Furthermore, the relative ease and short turnaround time (30 min) of this assay enables C. trachomatis-infected individuals to be treated without a diagnostic delay. CONCLUSIONS: This simple and novel test is a potential tool to screen a larger population, especially those in areas with limited resources.

Effects of aromatherapy on the anxiety, vital signs, and sleep quality of percutaneous coronary intervention patients in intensive care units.

The purpose of this study was to investigate the effects of aromatherapy on the anxiety, sleep, and blood pressure (BP) of percutaneous coronary intervention (PCI) patients in an intensive care unit (ICU). Fifty-six patients with PCI in ICU were evenly allocated to either the aromatherapy or conventional nursing care. Aromatherapy essential oils were blended with lavender, roman chamomile, and neroli with a 6 : 2 : 0.5 ratio. Participants received 10 times treatment before PCI, and the same essential oils were inhaled another 10 times after PCI. Outcome measures patients' state anxiety, sleeping quality, and BP. An aromatherapy group showed significantly low anxiety (t = 5.99, P < .001) and improving sleep quality (t = -3.65, P = .001) compared with conventional nursing intervention. The systolic BP of both groups did not show a significant difference by time or in a group-by-time interaction; however, a significant difference was observed between groups (F = 4.63, P = .036). The diastolic BP did not show any significant difference by time or by a group-by-time interaction; however, a significant difference was observed between groups (F = 6.93, P = .011). In conclusion, the aromatherapy effectively reduced the anxiety levels and increased the sleep quality of PCI patients admitted to the ICU. Aromatherapy may be used as an independent nursing intervention for reducing the anxiety levels and improving the sleep quality of PCI patients.

Effects of geranyl-phloroacetophenone on the induction of apoptosis and chemosensitization of adriamycin-resistant MCF-7 human breast cancer cells.

Polyphenols are known to induce apoptosis in many cancer cells and are proposed to be promising modulators of drug resistance. In the present study, we report that 3-geranyl-phloroacetophenone (3-GAP), a synthetic polyphenol, induces apoptosis and modulates drug resistance. In adriamycin-resistant MCF-7 human breast cancer (MCF-7/ADR) cells, which express a mutant form of p53, 3-GAP induced significant apoptosis, which was accompanied by no change in p53 transcriptional activity, but an increase in Bax expression, cyt c release, and activation of caspase-9, 7, and 3. In addition, 3-GAP significantly decreased the activity and expression level of glutathione S-transferase pi (GSTπ), a factor that induces drug resistance. Along with GSTπ inhibition, 3-GAP also induced a marked depletion of GSH, an endogenous antioxidant. The GST-inhibitory activity of 3-GAP correlated with the sensitization of MCF-7/ADR cells to doxorubicin. Under serum withdrawal conditions, the JNK inhibitor SP600125 significantly decreased the viability of the parent MCF-7 cells but not of MCF-7/ADR cells. In addition, the viability of 3-GAP-treated MCF-7/ADR cells was similar to those of MCF-7 cells treated with SP600125 alone or MCF-7/ADR cells co-treated with SP600125 and 3-GAP. These results indicate that JNK activity in MCF-7/ADR cells is halted by high levels of GSTπ, and that 3-GAP releases JNK from GSTπ's inhibition. In conclusion, 3-GAP induces apoptosis in and sensitizes drug-resistant MCF-7/ADR cells. These effects are mediated through p53-independent caspase-3 activation and reduction of the capacity for cellular antioxidants, such as GSTπ and GSH.

High-detectivity multilayer MoS(2) phototransistors with spectral response from ultraviolet to infrared.

Phototransistors based on multilayer MoS(2) crystals are demonstrated with a wider spectral response and higher photoresponsivity than single-layer MoS(2) phototransistors. Multilayer MoS(2) phototransistors further exhibit high room temperature mobilities (>70 cm(2) V(-1) s(-1) ), near-ideal subthreshold swings (~70 mV decade(-1) ), low operating gate biases (<5 V), and negligible shifts in the threshold voltages during illumination.

Poly(3-hexylthiophene)/multiwalled carbon hybrid coaxial nanotubes: nanoscale rectification and photovoltaic characteristics.

We fabricate hybrid coaxial nanotubes (NTs) of multiwalled carbon nanotubes (MWCNTs) coated with light-emitting poly(3-hexylthiophene) (P3HT). The p-type P3HT material with a thickness of approximately 20 nm is electrochemically deposited onto the surface of the MWCNT. The formation of hybrid coaxial NTs of the P3HT/MWCNT is confirmed by a transmission electron microscope, FT-IR, and Raman spectra. The optical and structural properties of the hybrid NTs are characterized using ultraviolet and visible absorption, Raman, and photoluminescence (PL) spectra where, it is shown that the PL intensity of the P3HT materials decreases after the hybridization with the MWCNTs. The current-voltage (I-V) characteristics of the outer P3HT single NT show the semiconducting behavior, while ohmic behavior is observed for the inner single MWCNT. The I-V characteristics of the hybrid junction between the outer P3HT NT and the inner MWCNT, for the hybrid single NT, exhibit the characteristics of a diode (i.e., rectification), whose efficiency is clearly enhanced with light irradiation. The rectification effect of the hybrid single NT has been analyzed in terms of charge tunneling models. The quasi-photovoltaic effect is also observed at low bias for the P3HT/MWCNT hybrid single NT.