Diagnosis and treatment of nail melanoma: a review of the clinicopathologic, dermoscopic, and genetic characteristics.

Nail melanoma (NM) is an important differential diagnosis in patients with longitudinal melanonychia. However, diagnosis is often challenging as it is difficult to differentiate from other pigmented nail disorders. The main challenge for diagnosis is obtaining adequate nail matrix biopsy specimens for histopathological assessment. Furthermore, the histopathological changes in the early stages of NM are subtle and contribute to a delay in diagnosis and care. Therefore, the integration of clinical and histopathological analyses is essential. Clinical and dermoscopic features, such as a broadened width of asymmetric bands in an irregular pattern, with multicolour pigmentation, periungual pigmentation, and continuous growth, are features that support the diagnosis of NM. The essential histological features that must be assessed are cellular morphology, architectural features, melanocyte density, and inflammatory changes. The reported mutations in NMs were BRAF (0-43%), NRAS (0-31%), KIT (0-50%), NF1 (0-50%), and GNAQ (0-25%). Surgery is the primary treatment for NM. The recommended treatment for in situ or minimally invasive NM is functional surgery, but cases with suspected bone invasion should be treated with amputation. Targeted therapy and immunotherapy are indicated for advanced stages of NM. This review summarizes the updated guidelines for the diagnosis and treatment of NM.

Improving the bioavailability of manganese and meat quality of broilers by using hot-melt extrusion nano method.

1. Mineral excretion is an issue in the poultry industry. The use of micro minerals in nano form can increase bioavailability and decrease excretion rate. However, information concerning the bioavailability of nano manganese (Mn) in broiler chicks is limited.2. This experiment studied the influences of hot-melt extrusion (HME)-processed manganese sulphate on body weight gain, Mn bioavailability, nutrient digestibility and meat quality in broiler chicks fed a corn-soybean meal-based diet as a starter and grower phase. A total of 700 birds (Ross 308, 1-day-old) were randomly placed in 35 cages (20 birds per cage). The broiler chicks were fed one of seven experimental diets, which consisted of a control (without supplemental Mn), different levels of MnSO4 (IN-Mn60; 60, 120, and 200 mg/kg), or HME MnSO4 (HME-Mn; 60, 120, and 200 mg/kg).3. There was an increased serum Mn content in broilers fed diet supplemented with HME-Mn. In the grower phase, increased dietary Mn levels elevated the concentrations in the serum, liver, and tibia. There were increases in the excreta Mn content of broilers fed increasing levels. The supplementation of HME-Mn showed a lower percentage of abdominal fat compared with the IN-Mn treatment diets. Supplementation with HME-Mn decreased intramuscular fat compared with the diets supplemented with IN-Mn. The supplementation of HME-Mn decreased the thiobarbituric acid reactive substances (TBARS) at d 6 of age. The HME-Mn source showed a greater decrease in TBARS compared with the IN-Mn treatment.4. In conclusion, HME processing increased bioavailability and could be used as an environmentally friendly method to facilitate lower levels of Mn in the diet of broiler chickens.

Developing a predictive model for distinguishing invasive nail unit melanoma from nail unit melanoma in situ.

BACKGROUND: Clinical information that distinguishes invasive nail unit melanoma from nail unit melanoma in situ before surgery would aid physicians in the decision-making process and estimating prognosis. However, limited information is available on the detailed demographic and dermoscopic features of invasive nail unit melanoma and nail unit melanoma in situ for differential diagnosis. OBJECTIVE: This study aimed to investigate the demographic data and dermoscopic features of invasive nail unit melanoma and nail unit melanoma in situ and establish a predictive model for differentiating these two forms of nail unit melanoma. METHODS: A retrospective observational study of ninety-seven patients diagnosed with nail unit melanoma (59 in situ and 38 invasive cases) in four healthcare centres in South Korea (three tertiary referral hospitals and one second referral hospital) from March 2014 to December 2019. RESULTS: A multivariable analysis revealed that ulcer (odds ratio = 21.6, confidence interval = 2.1-219.8, P = 0.009), total melanonychia (odds ratio = 17.6, confidence interval = 3.0-104.0, P = 0.002), nail plate destruction (odds ratio = 10.9, confidence interval = 2.0-59.4, P = 0.006) and polychromia (odds ratio = 5.3, confidence interval = 1.36-20.57, P = 0.016) were distinctive dermoscopic features of invasive nail unit melanoma. A predictive model with scores ranging from 0 to 6 points demonstrated a reliable diagnostic value (C-statistic = 0.902) in differentiating invasive nail unit melanoma from nail unit melanoma in situ. CONCLUSIONS: Invasive nail unit melanoma and nail unit melanoma in situ have different dermoscopic features. A predictive model based on morphologic dermoscopic features could aid in differentiating invasive nail unit melanoma from nail unit melanoma in situ.

Dermatologist-level classification of malignant lip diseases using a deep convolutional neural network.

BACKGROUND: Deep convolutional neural networks (DCNNs) can classify skin diseases at a level equivalent to a dermatologist, but their performance in specific areas requires further research. OBJECTIVE: To evaluate the performance of a trained DCNN-based algorithm in classifying benign and malignant lip diseases. METHODS: A training set of 1629 images (743 malignant, 886 benign) was used with Inception-Resnet-V2. Performance was evaluated using another set of 344 images and 281 images from other hospitals. Classifications by 44 participants (six board-certified dermatologists, 12 dermatology residents, nine medical doctors not specialized in dermatology and 17 medical students) were used for comparison. RESULTS: The outcomes based on the area under curve, sensitivity and specificity were 0·827 [95% confidence interval (CI) 0·782-0·873], 0·755 (95% CI 0·673-0·827) and 0·803 (95% CI 0·752-0·855), respectively, for the set of 344 images; and 0·774 (95% CI 0·699-0·849), 0·702 (95% CI 0·579-0·808) and 0·759 (95% CI 0·701-0·813), respectively, for the set of 281 images. The DCNN was equivalent to the dermatologists and superior to the nondermatologists in classifying malignancy. After referencing the DCNN result, the mean ± SD Youden index increased significantly for nondermatologists, from 0·201 ± 0·156 to 0·322 ± 0·141 (P < 0·001). CONCLUSIONS: DCNNs can classify lip diseases at a level similar to dermatologists. This will help unskilled physicians discriminate between benign and malignant lip diseases. What's already known about this topic? Deep convolutional neural networks (DCNNs) can classify malignant and benign skin diseases at a level equivalent to dermatologists. The lips are a unique feature in terms of histology and morphology. Previous studies of DCNNs have not investigated tumours on specific locations. What does this study add? This study shows that DCNNs can distinguish rare malignant and benign lip disorders at the same rate as dermatologists. DCNNs can help nondermatologists to distinguish malignant lip diseases. What are the clinical implications of this work? DCNNs can distinguish malignant and benign skin diseases even at specific locations such as the lips, as well as board-certified dermatologists. Malignant lip diseases are rare and difficult for less trained doctors to differentiate them from benign lesions. This study shows that in dermatology, DCNN can help improve decision-making processes for rare skin diseases in specific areas of the body.

Asymptomatic solitary mass on the sacral region.

Nuchal-type fibroma (NTF) is a rare, benign, tumour-like fibrous proliferation of unknown pathogenesis. Despite the name, approximately one-third of cases occur at extranuchal sites. We report a rare case of NTF of the sacral region, an extremely uncommon extranuchal site. As NTF is often misdiagnosed because of its rarity and histopathological similarity with other fibrous tumours, we present this case to increase understanding of this rare disease entity.

Contemporary Management of Patients with Concomitant Coronary and Carotid Artery Disease.

The ideal management of concomitant carotid and coronary artery occlusive disease remains elusive. Although researchers have advocated the potential benefits of varying treatment strategies based on either concomitant or staged surgical treatment, there is no consensus in treatment guidelines among national or international clinical societies. Clinical studies show that coronary artery bypass grafting (CABG) with either staged or synchronous carotid endarterectomy (CEA) is associated with a high procedural stroke or death rate. Recent clinical studies have found carotid artery stenting (CAS) prior to CABG can lead to superior treatment outcomes in asymptomatic patients who are deemed high risk of CEA. With emerging data suggesting favorable outcome of CAS compared to CEA in patients with critical coronary artery disease, physicians must consider these diverging therapeutic options when treating patients with concurrent carotid and coronary disease. This review examines the available clinical data on therapeutic strategies in patients with concomitant carotid and coronary artery disease. A treatment paradigm for considering CAS or CEA as well as CABG and percutaneous coronary intervention is discussed.

Thromboembolic Risk of Endovascular Intervention for Lower Extremity Deep Venous Thrombosis.

BACKGROUND: This study evaluated the risk of thromboembolism during endovascular interventions in patients with symptomatic lower extremity deep vein thrombosis (DVT) METHODS: Clinical records of all patients who underwent endovascular interventions for symptomatic lower extremity DVT from 2001 to 2017 were retrospectively analyzed using a prospectively maintained database. Only patients who received an inferior vena cava (IVC) filter were included in the analysis. Trapped intrafilter thrombus was assessed for procedure-related thromboembolism. Clinical outcomes of thrombus management and thromboembolism risk were analyzed. RESULTS: A total 172 patients (mean age 57.4 years, 98 females) who underwent 174 endovascular DVT interventions were included in the analysis. Treatment strategies included thrombolytic therapy (64%), mechanical thrombectomy (n = 86%), pharmacomechanical thrombolysis (51%), balloon angioplasty (98%), and stent placement (28%). Thrombectomy device used included AngioJet (56%), Trellis (19%), and Aspire (11%). Trapped IVC filter thrombus was identified in 58 patients (38%) based on the IVC venogram. No patient developed clinically evident pulmonary embolism (PE). IVC filter retrieval was performed in 98 patients (56%, mean 11.8 months after implantation). Multivariate analysis showed that iliac vein occlusion (P = 0.04) was predictive for procedure-related thromboembolism. CONCLUSIONS: Iliac vein thrombotic occlusion is associated with an increased thromboembolic risk in DVT intervention. Retrievable IVC filter should be considered when performing percutaneous thrombectomy in patients with iliac venous occlusion to prevent PE.

The clinical and histopathological characteristics of early-onset basal cell carcinoma in Asians.

BACKGROUND: Basal cell carcinoma (BCC) is by far the most common cancer in white populations. In addition, recent reports have demonstrated an increasing incidence of BCC in Korea. We have observed a significant number of early-onset BCC cases in which the disease occurred in patients younger than 50 years. OBJECTIVE: To investigate the clinicopathological characteristics of early-onset BCC in an Asian population, specifically in Koreans. METHODS: One hundred and five patients with early-onset BCC were enrolled from a total of 1047 BCC patients who underwent surgery between January 1997 and December 2014 (942 patients over the age of 50 years were designated as the control group). RESULTS: Early-onset BCC accounted for 10.03% of all 1047 cases and the incidence over time displayed an incremental trend. The early-onset group displayed similar results as the control group, with a predominance of female BCC patients and the majority of tumours displaying the following characteristics: small in size, occurring in sun-exposed areas and belonging to the noduloulcerative clinical subtype and nodular histopathological subtype. In comparison with a previous study in a Western population, the incidence of the disease in non-exposed areas of the body, as well as the proportion of tumours of the superficial histological subtype, were lower in Asian patients. CONCLUSION: Although the clinicopathological characteristics of BCC are well-known, these characteristics have not been determined for early-onset BCC in an Asian population. Therefore, this study is the first report on early-onset BCC in Asians, specifically in a Korean patient group.

Primary ovarian malignant mixed mesodermal tumor: report of four cases.

Malignant mixed mesodermal tumors (MMMTs) are highly aggressive and usually diagnosed at advanced stages. MMMT originates from either the ovary or the uterus. Because this disease is relatively rare, an optimal treatment modality has not yet been established. The authors report four cases of ovarian MMMT (one heterologous MMMT and three homologous MMMTs) during 1990-2011. The patients underwent operation immediately after histopathologically confirmation and were treated with platinum-based combination chemotherapy. The extent of operation, the outcomes of radiation therapy, and the proper chemotherapeutic regimen are still controversial. The authors report herein four cases of ovarian MMMTs alone with a brief literature review.

Development of a liquid-helium free cryogenic sample holder with mK temperature control for autonomous electron microscopy.

The automated and autonomous cryogenic transmission electron microscopy (Cryo-EM) demands a sample holder capable of maintaining temperatures below 10 K with precise control, long holding times, and minimal helium use. Rising to this challenge, we initiated an ambitious project to develop a novel closed-cycle cryocooler-based cryogenic sample holder that operates without the use of liquid helium and the consumption of gaseous helium. This article presents the design, construction, and experimental testing of the initial prototype, which achieves an ultimate temperature of 5.6 K with exceptional stability close to 1mK, while providing a wide temperature control range from 295 K to 5.6 K, marking a clear advancement in cryo-EM holder development. While the prototype was not designed for atomic resolution imaging and thus lacks a sturdy support system to mitigate mechanical vibrations from the cryocooler's pulsed tube, this innovative approach successfully demonstrates proof of concept. It offers unprecedented capabilities for state-of-the-art cryogenic microscopy and microanalysis in materials and biological sciences.

Dermoscopy of subungual haemorrhage: its usefulness in differential diagnosis from nail-unit melanoma.

BACKGROUND: Subungual haemorrhages are characterized by well-circumscribed dots or blotches with a red to red-black pigmentation, but some cases can be difficult to distinguish from subungual melanoma by the naked eye alone. Dermoscopy has proven to be a useful, noninvasive tool in the diagnosis of pigmented lesions in the nail; however, few dermoscopic studies of subungual haemorrhages have been reported. OBJECTIVES: To investigate characteristic dermoscopic patterns of subungual haemorrhages, and to find distinctive features that can differentiate them from nail-unit melanomas. METHODS: Patients with a confirmed diagnosis of either subungual haemorrhage or nail-unit melanoma at a tertiary university hospital were included in the study. Clinical features and dermoscopic patterns were evaluated. RESULTS: Sixty-four patients with a total of 90 lesions of subungual haemorrhage were enrolled in the study. The majority of cases (84%) showed combinations of more than one colour, while 16% had only one colour. The most common colour of the subungual haemorrhages was purple-black, in 37% of cases. A homogeneous pattern was observed in 92% of cases, globular patterns in 42% and streaks in 39%. Peripheral fading and periungual haemorrhages were found in 54% and 22% of cases, respectively. Destruction or dystrophy of the nail plate was observed in 16% of cases. In the 16 cases of nail-unit melanomas, Hutchinson sign, longitudinal irregular bands or lines, triangular shape of bands, vascular pattern, and ulcerations were found in 100%, 81%, 25%, 6% and 81% of cases, respectively. In contrast, these features were not found in subungual haemorrhages. CONCLUSIONS: Dermoscopy provides valuable information for the diagnosis of subungual haemorrhage and aids in the differential diagnosis from nail-unit melanoma.

The use of dermatoscopy to monitor therapeutic response of Bowen disease: a dermatoscopic pathological study.

BACKGROUND: Dermatoscopy is a noninvasive technique that can be helpful in the diagnosis of pigmented and nonpigmented skin tumours. The dermatoscopic evaluation of Bowen disease (BD) improves diagnostic accuracy. OBJECTIVE: To evaluate the usefulness of dermatoscopy as a tool for assessing responses to therapy and recurrence of BD. METHODS: Patients with histopathologically diagnosed BD were prospectively enrolled. In all lesions, 3 months after the end of treatment (photodynamic therapy or 5% imiquimod cream), dermatoscopic and histopathological examinations were repeated to evaluate and correlate changes in dermatoscopic features and histopathological results. Cured lesions were monitored using dermatoscopy during the follow-up period. RESULTS: A total of 23 patients with 29 histopathologically diagnosed BD lesions were included in this study. After treatment, dermatoscopic examination revealed the disappearance of pre-existing vascular structures in 16 lesions, and remaining vascular structures in 13 lesions. Histopathological evaluation of the treated lesions showed remnant intraepithelial neoplasms and increased dermal vascularity in lesions with persistent dermatoscopic vascular structures. However, normal epidermis and decreased dermal vascularity were observed in all but one of the lesions without previous dermatoscopic vascular structures. During the follow-up period, one lesion showed reappearance of previous vascular structures on dermatoscopy 9 months after treatment. Histopathological examination confirmed the recurrence of BD. CONCLUSIONS: Our study demonstrates that the persistence of dermatoscopic vascular structures of BD appears to be associated with residual disease, and disappearance of vascular structures suggests that the disease has been cured. In addition, reappearance of previous dermatoscopic vascular structures indicates the recurrence of BD. Therefore, we suggest that dermatoscopy can be a useful, reliable and noninvasive tool in the therapeutic follow-up of BD.

Novel anti-wrinkle effect of cosmeceutical product with new retinyl retinoate microsphere using biodegradable polymer.

BACKGROUND: The novel hybrid retinoid, retinyl retinoate, is a synthetic material that was designed to reduce the side effects of retinoic acid and to increase the stability of retinol. The formulation of the retinyl retinoate, however, is required to enhance skin permeation, and thus to increase the anti-wrinkle effect. AIM: To identify the efficacy of retinyl retinoate microsphere using biodegradable polymer as an anti-aging agent of cosmetics in treating females over 30 years old with periorbital wrinkles. METHODS: The retinyl retinoate microsphere was prepared using the biodegradable polymer; polylactic acid (PLA). We also conducted two clinical studies with a total of 44 Korean women for 12 weeks. In the first clinical study, 20 patients completed a 12-week trial of cream A [3% PLA-retinyl retinoate (2%) microsphere] applied twice daily to the face. In the second clinical study, 24 patients completed a 12-week trial of cream B (0.06% retinyl retinoate) applied twice daily to the face. Efficacy was based on a global photodamage score, photographs, and image analysis using replicas and Visiometers every 4 weeks. RESULTS: The PLA-retinyl retinoate microsphere was more effective for the permeation of retinyl retinoate than retinyl retinoate in itself. The cream A, which contains 3% PLA-retinyl retinoate (2%) microsphere, showed a statistically significant improvement in facial wrinkles (P<0.05) in 20 volunteers after only 4 weeks of application in a clinical trial test. The visual wrinkle improvement and the maximum roughness improvement rate (R2) for cream A was 6.05%, 8.03% higher than that of cream B which contains 0.06% retinyl retinoate, after 4 weeks. CONCLUSION: Retinyl retinoate has a potent anti-wrinkle activity, and the PLA-retinyl retinoate microsphere could be a useful cosmeceutical product for anti-aging purposes.

Design and operational parameters of a rooftop rainwater harvesting system: definition, sensitivity and verification.

The appropriate design and evaluation of a rainwater harvesting (RWH) system is necessary to improve system performance and the stability of the water supply. The main design parameters (DPs) of an RWH system are rainfall, catchment area, collection efficiency, tank volume and water demand. Its operational parameters (OPs) include rainwater use efficiency (RUE), water saving efficiency (WSE) and cycle number (CN). The sensitivity analysis of a rooftop RWH system's DPs to its OPs reveals that the ratio of tank volume to catchment area (V/A) for an RWH system in Seoul, South Korea is recommended between 0.03 and 0.08 in terms of rate of change in RUE. The appropriate design value of V/A is varied with D/A. The extra tank volume up to V/A of 0.15∼0.2 is also available, if necessary to secure more water. Accordingly, we should figure out suitable value or range of DPs based on the sensitivity analysis to optimize design of an RWH system or improve operation efficiency. The operational data employed in this study, which was carried out to validate the design and evaluation method of an RWH system, were obtained from the system in use at a dormitory complex at Seoul National University (SNU) in Korea. The results of these operational data are in good agreement with those used in the initial simulation. The proposed method and the results of this research will be useful in evaluating and comparing the performance of RWH systems. It is found that RUE can be increased by expanding the variety of rainwater uses, particularly in the high rainfall season.

Basic studies toward ultrafast soft x-ray photoelectron diffraction; its application to probing local structure in iodobenzene molecules.

Ultrafast x-ray photoelectron diffraction (UXPD) for free molecules has a promising potential to probe the local structures of the molecules in an element-specific fashion. Our UXPD scheme consists of three steps: (1) near-infrared laser (NIR) with ns pulse duration aligns sample molecules, (2) ultra-violet laser with fs pulse duration pumps the aligned molecules, and (3) soft x-ray free-electron laser (SXFEL) with fs pulse duration probes the molecules by measuring x-ray photoelectron diffraction (XPD) profiles. Employing steps of (1) and (3), we have measured I 3d XPD profiles from ground state iodobenzene aligned by the NIR laser with the SXFEL. Then, we have intensively calculated I 3d XPD profiles with density functional theory, taking degrees of alignments of the molecules into account, to extract a distance between C and I atoms in iodobenzene from the experimental I 3d XPD profiles. Although we have failed to determine the distance from the comparison between the experimental and theoretical results, we have succeeded in concluding that the degeneracies of the initial state eliminate the sensitivity on molecular structure in the I 3d XPD profiles. Thus, the observation of fine structures in the XPD profiles could be expected, if a nondegenerate molecular orbital is selected for a probe of UXPD. Finally, we have summarized our criteria to perform UXPD successfully: (1) to use SXFEL, (2) to prepare sample molecules with the degree of alignment higher than 0.8, and (3) to select a photoemission process from a nondegenerate inner-shell orbital of sample molecules.