Primary Cutaneous Apocrine Carcinoma and Syringocystadenoma Papilliferum Arising in Nevus Sebaceus: A Case Report and Review of the Literature.

Nevus sebaceus is a hamartomatous lesion characterized by epidermal, follicular, sebaceus, and apocrine gland abnormalities. Approximately 25% of affected individuals may develop benign or malignant secondary neoplasms within the preceding nevus sebaceus. Primary cutaneous apocrine carcinoma (PCAC) is a rare malignant skin tumor affecting elderly adults in their sixth decade of life. Histologically, PCAC appears as a dermal tumor displaying apocrine differentiation with decapitation secretion and malignant features. Secondary malignancy arising from nevus sebaceus is a rare complication, especially for apocrine carcinoma. To date, approximately 200 cases of PCAC have been reported in the literature, and only a few cases have developed PCAC on the scalp. Very few cases (approximately only 12) of PCACs developing in nevus sebaceus have been reported. Here, we report an extremely rare case of the coexistence of PCAC and syringocystadenoma papilliferum arising within nevus sebaceus of the scalp.

Hereditary Leiomyomatosis and Renal Cell Cancer: A Case Report of Pilar Leiomyomatosis with History of Kidney Cancer and Review of the Literature.

Pilar leiomyoma or piloleiomyoma is a benign neoplasm of the smooth muscle arising from the arrector pili muscle. It manifests as brown to red firm papulonodules with sites of predilection being the face, trunk, and extensor surfaces of the extremities. Histologically, the lesions exhibit ill-defined dermal tumors with interlacing fascicles of spindle cells. Some genodermatoses are characterized by the development of visceral tumors and cutaneous leiomyomatosis such as Reed's syndrome, and hereditary leiomyomatosis and renal cell cancer (HLRCC). A 55-year-old male presented with reddish-brown papules and nodules on the face and upper back, accompanied by sharp episodic pain on the face. He had undergone nephrectomy for renal cancer 9 years ago, and his younger brother had similar cutaneous manifestation. Histopathologic findings were consistent with pilar leiomyoma, showing bundles of smooth muscle tumors in the dermis. Based on the clinical information including clinical features, past medical history, and family history, HLRCC was highly suspected. To confirm the diagnosis, whole exome sequencing was performed using peripheral blood, which revealed a novel point mutation (c.739G>A, p.Glu247Lys) in the fumarate hydratase (FH) gene. We describe a confirmed case of HLRCC, which is a genetic disorder with a potential to cause visceral cancers, which dermatologists might overlook as a benign condition.

Needleless laser injector versus needle injection for skin enhancement and rejuvenation effect of dermal filler.

BACKGROUND AND OBJECTIVES: A needleless laser-induced microjet injector is a novel transdermal drug delivery system that can rapidly inject a very small and precise drug dose into the skin with minimal pain and downtime. In this study, we aimed to compare the laser-induced microjet injection versus needle injection of polylactic acid/hyaluronic acid filler for skin enhancement and rejuvenation. PATIENTS AND METHODS: A 24-week prospective, single-center, assessor-blinded, randomized, split-face study was conducted. The enrolled patients underwent one treatment session of dermal filler injection using a laser-induced microjet injector on one half of the face or a traditional needle injection on the other half of the face. Evaluation was conducted at baseline before treatment and at 4, 12, and 24 weeks after treatment. RESULTS: A single treatment of filler injection with a laser-induced microjet injector resulted in similar improvements in skin hydration and elasticity as a single treatment of filler injection by using manual needle injection, with reduced pain, side effects, and decreased treatment time. CONCLUSIONS: Laser-induced microjet injector enabled not only the application of a controlled dose and filler depth but also even distribution, improved clinical efficacy, reduced pain and side effects, and sufficient time for clinicians to perform treatment.

Neuroprotective effects of melatonin in neurodegenerative and autoimmune central nervous system diseases.

The suprachiasmatic nucleus (SCN) in the anterior hypothalamus is the major circadian pacemaker in humans. Melatonin is a key hormone secreted by the pineal gland in response to darkness. Light-induced stimuli are transmitted along the retinohypothalamic tract to the SCN. Activation of the SCN inhibits the production of melatonin by the pineal gland through a complex neural pathway passing through the superior cervical ganglion. Accordingly, when light is unavailable, the pineal gland secretes melatonin. The circadian rhythm modulates sleep-wake cycles as well as many physiological functions of the endocrine system, including core body temperature, pulse rate, oxygen consumption, hormone levels, metabolism, and gastrointestinal function. In neurodegenerative disorders, the sleep-wake cycle is disrupted and circadian regulation is altered, which accelerates disease progression, further disrupting circadian regulation and setting up a vicious cycle. Melatonin plays a critical role in the regulation of circadian rhythms and is a multifunctional pleiotropic agent with broad neuroprotective effects in neurodegenerative disorders, viral or autoimmune diseases, and cancer. In this review, I discuss the neuroprotective functions of melatonin in circadian regulation and its roles in promoting anti-inflammatory activity, enhancing immune system functions, and preventing alterations in glucose metabolism and mitochondrial dysfunction in neurodegenerative disorders and autoimmune central nervous system diseases.

Change of iron content in brain regions after intravenous iron therapy in restless legs syndrome: quantitative susceptibility mapping study.

STUDY OBJECTIVES: The pathomechanism of restless legs syndrome (RLS) is related to brain iron deficiency and iron therapy is effective for RLS; however, the effect of iron therapy on human brain iron state has never been studied with magnetic resonance imaging. This study aimed to investigate the change of brain iron concentrations in patients with RLS after intravenous iron therapy using quantitative susceptibility mapping (QSM). METHODS: We enrolled 31 RLS patients and 20 healthy controls. All participants underwent initial baseline (t0) assessment using brain magnetic resonance imaging, serum iron status, and sleep questionnaires including international RLS Study Group rating scale (IRLS). RLS patients underwent follow-up tests at 6 and 24 weeks (t1 and t2) after receiving 1000 mg ferric carboxymaltose. Iron content of region-of-interest on QSM images was measured for 13 neural substrates using the fixed-shaped method. RESULTS: RLS symptoms evaluated using IRLS were significantly improved after iron treatment (t0: 29.7 ± 6.5, t1: 19.5 ± 8.5, t2: 21.3 ± 10.1; p < .001). There was no significant difference in susceptibility values between the controls and RLS patients at t0. In the caudate nucleus, putamen, and pulvinar thalamus of RLS patients, the QSM values differed significantly for three timepoints (p = .035, .048, and .032, respectively). The post-hoc analysis revealed that the QSM values increased at t1 in the caudate nucleus (66.8 ± 18.0 vs 76.4 ± 16.6, p = .037) and decreased from t1 to t2 in the putamen (69.4 ± 16.3 vs 62.5 ± 13.6, p = .025). Changes in the QSM values for the pulvinar and caudate nuclei at t1 were positively and negatively correlated with symptomatic improvement, respectively (r = 0.361 and -0.466, respectively). CONCLUSIONS: Intravenous iron treatment results in changes in brain iron content which correlate to reductions in RLS severity. This suggests a connection between symptom improvement and the associated specific brain regions constituting the sensorimotor network.

A Randomized Split-Face Study of Photodynamic Therapy With St. John's Wort and Indole-3-Acetic Acid for the Treatment of Acne.

BACKGROUND: St. John's wort (SJW) contains hypericin, a powerful photosensitizer with antimicrobial and anti-inflammatory activities. OBJECTIVE: To compare the efficacy and safety of SJW-photodynamic therapy (PDT) with that of indole-3-acetic acid (IAA)-PDT for the treatment of acne and investigate the skin rejuvenating effects of SJW-PDT. MATERIALS AND METHODS: In vitro experiments were conducted to examine the generation of reactive oxygen species and the antimicrobial effects of SJW-PDT. In the prospective, double-blind, split-face, randomized study, 31 patients with facial acne were treated with SJW or IAA with simultaneous illumination of red light and green light. RESULTS: SJW produces free radicals with visible light irradiation, and the growth of Cutibacterium acnes and Staphylococcus aureus is significantly suppressed. One week after the last treatment, the acne lesion counts were significantly decreased in both groups (56.5% reduction in SJW, p < .001 vs 57.0% in IAA, p < .001). Significant reductions in sebum secretion, erythema index, roughness, and wrinkles were observed in both groups after the treatment. No side effects were observed. CONCLUSION: SJW-PDT is a simple, safe, and effective treatment option for acne that is also beneficial for skin rejuvenation.

Efficacy and Safety of the Micro-insulated Needle Radiofrequency Device for Reduction of Submental Fat.

BACKGROUND: Recently, it has been reported that a micro-insulated needle radiofrequency (RF) system is effective at achieving subcutaneous fat reduction; however, no study has yet applied this technique to reduce submental fat. OBJECTIVE: To evaluate the efficacy and safety of a fractional RF device with a micro-insulated needle to reduce submental fat. MATERIALS AND METHODS: In this prospective, single-blinded, pre-post comparative study, 24 adults with excess submental fat were treated once using a micro-insulated needle RF device. Outcomes included efficacy (submental fat rating by an independent investigator, fat volume quantified with a 3-dimensional camera, and patient satisfaction), assessed 1 and 2 months after the procedure, and safety (adverse events), assessed throughout the study. RESULTS: The patients' Physician-Assisted Submental Fat Rating Scale score significantly decreased after 1 month and further decreased after 2 months. The average volume of submental fat was significantly decreased after 2 months (20.44 ± 5.53 cc to 16.41 ± 4.58 cc, p < .001). Patient satisfaction was high. Transient and mild local skin reactions without long-term sequelae were observed in 4 patients. CONCLUSION: The micro-insulated needle RF device is beneficial for the reduction of submental fat and has tolerable safety profiles. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05517824.

Early Postoperative Injections of Polydeoxyribonucleotide Prevent Hypertrophic Scarring After Thyroidectomy: A Randomized Controlled Trial.

Objective: Polydeoxyribonucleotide (PDRN) is known to enhance wound healing, but there has been no clinical trial investigating the effect of PDRN on scar prevention in surgical wounds. This study aimed to evaluate the efficacy of PDRN administration in preventing postoperative scars. Approach: In this randomized controlled trial (NCT05149118), 44 patients who underwent open thyroidectomy were randomly assigned to the PDRN treatment or untreated control group. Only patients in the treatment group received two consecutive injections of PDRN 1 and 2 days after surgery. The modified Vancouver Scar Scale (mVSS), patients' subjective symptoms, erythema index (EI), melanin index (MI), and scar height were assessed 3 months after surgery. Results: Patients in the treatment group had lower mVSS scores (1.619 ± 1.244 vs. 2.500 ± 1.540, respectively; p = 0.059) and a significantly lower vascularity subscore (0.476 ± 0.512 vs. 0.900 ± 0.447, respectively; p = 0.010) than those in the control group at the 3-month follow-up. Compared with the control group, the level of subjective symptoms, EI, and scar height were all significantly lowered in the PDRN injection group. No specific side effects related to PDRN injection were observed. Innovation: This is the first clinical study that demonstrated that PDRN injections rapidly decreased postsurgical wound erythema and as a result, significantly reduced both excessive scar formation and accompanying symptoms. Conclusion: Early postoperative injection of PDRN is an effective and safe treatment to prevent hypertrophic scars and improve scar outcomes.

The degradation of performance of a state-of-the-art skin image classifier when applied to patient-driven internet search.

Model Dermatology ( https://modelderm.com ; Build2021) is a publicly testable neural network that can classify 184 skin disorders. We aimed to investigate whether our algorithm can classify clinical images of an Internet community along with tertiary care center datasets. Consecutive images from an Internet skin cancer community ('RD' dataset, 1,282 images posted between 25 January 2020 to 30 July 2021; https://reddit.com/r/melanoma ) were analyzed retrospectively, along with hospital datasets (Edinburgh dataset, 1,300 images; SNU dataset, 2,101 images; TeleDerm dataset, 340 consecutive images). The algorithm's performance was equivalent to that of dermatologists in the curated clinical datasets (Edinburgh and SNU datasets). However, its performance deteriorated in the RD and TeleDerm datasets because of insufficient image quality and the presence of out-of-distribution disorders, respectively. For the RD dataset, the algorithm's Top-1/3 accuracy (39.2%/67.2%) and AUC (0.800) were equivalent to that of general physicians (36.8%/52.9%). It was more accurate than that of the laypersons using random Internet searches (19.2%/24.4%). The Top-1/3 accuracy was affected by inadequate image quality (adequate = 43.2%/71.3% versus inadequate = 32.9%/60.8%), whereas participant performance did not deteriorate (adequate = 35.8%/52.7% vs. inadequate = 38.4%/53.3%). In this report, the algorithm performance was significantly affected by the change of the intended settings, which implies that AI algorithms at dermatologist-level, in-distribution setting, may not be able to show the same level of performance in with out-of-distribution settings.

Early diagnosis of Gaucher disease in Korean patients with unexplained splenomegaly: a multicenter observational study.

Background: Gaucher disease (GD) is an autosomal recessive disorder characterized by excessive accumulation of glucosylceramide in multiple organs. This study was performed to determine the detection rate of GD in a selected patient population with unexplained splenomegaly in Korea. Methods: This was a multicenter, observational study conducted at 18 sites in Korea between December 2016 and February 2020. Adult patients with unexplained splenomegaly were enrolled and tested for ß-glucosidase enzyme activity on dried blood spots (DBS) and in peripheral blood leukocytes. Mutation analysis was performed if the test was positive or indeterminate for the enzyme assay. The primary endpoint was the percentage of patients with GD in patients with unexplained splenomegaly. Results: A total of 352 patients were enrolled in this study (male patients, 199; mean age, 48.42 yr). Amongst them, 14.77% of patients had concomitant hepatomegaly. The most common sign related to GD was splenomegaly (100%), followed by thrombocytopenia (44.32%) and, anemia (40.91%). The ß-glucosidase activity assay on DBS and peripheral leukocytes showed abnormal results in sixteen and six patients, respectively. Eight patients were tested for the mutation, seven of whom were negative and one patient showed a positive mutation analysis result. One female patient who presented with splenomegaly and thrombocytopenia was diagnosed with type 1 GD. The detection rate of GD was 0.2841% (exact 95% CI, 0.0072‒1.5726). Conclusion: The detection rate of GD in probable high-risk patients in Korea was lower than expected. However, the role of hemato-oncologists is still important in the diagnosis of GD.

Basal cell carcinoma of the scalp shows distinct features from the face in Asians.

Basal cell carcinoma (BCC) affecting different sites has been reported to have different clinicopathological features. In previous studies, the scalp was commonly classified to the head and neck region. However, the scalp has distinct characteristics from those of other parts of the skin. We retrospectively reviewed the medical records of patients who underwent surgical treatment for BCC. A total of 734 lesions were examined, and 13.2% originated from the scalp. The nodular type was the most common histologic subtype; however, the proportion of the superficial type was significantly higher than that of facial BCC (p < 0.001). Compared with facial BCC, younger age (p = 0.046) and larger tumor size (p < 0.001) were observed in scalp BCC. These characteristics were similar to those of truncal BCC in that they demonstrated a higher proportion of the superficial type (p < 0.001), younger age (p = 0.001), and larger tumor diameter (p < 0.001) compared with BCC in the head and neck region. Scalp BCC and truncal BCC were not significantly different in terms of age (p = 0.052) and tumor size (p = 0.230). In conclusion, despite the anatomical proximity, features of scalp BCC were similar to those of truncal lesions compared with facial lesions. Scalp BCC might be a separate entity from facial BCC.

Augmenting the accuracy of trainee doctors in diagnosing skin lesions suspected of skin neoplasms in a real-world setting: A prospective controlled before-and-after study.

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.

Clinical Implication of the Regional Thickness of the Lower Facial Skin, Superficial Fat, and Superficial Musculoaponeurotic System on High-Intensity Focused Ultrasound Treatment.

BACKGROUND: Knowledge of the topographic thickness of the skin and soft tissues is necessary when performing a high-intensity focused ultrasound (HIFU) procedure. Thermal tissue injury to the superficial musculoaponeurotic system (SMAS) or deeper can injure the facial nerve and its branches. OBJECTIVE: To demonstrate the topographic thickness of the lower facial skin, superficial fat, and SMAS. MATERIALS AND METHODS: The ultrasound data of 200 healthy patients who underwent lower facial rejuvenation were retrospectively reviewed. RESULTS: The mean age was 41.1 ± 13.7 years (range, 19-76 years). The jowl had thinner skin, thicker superficial fat, and deeper superficial and deep margins of the SMAS than the preauricle or lower cheek. The thickness of the superficial fat decreased with age, especially on the preauricle, lower cheek, and jowl. Women had thicker superficial fat than men on the preauricle and lower cheek. The superficial and deep margins of the SMAS were located more superficially in old and male patients with a slim facial figure than in young and female patients with a chubby facial figure. CONCLUSION: The present findings provide anatomical information regarding the superficial fat and SMAS, which is useful in determining the focal penetration depth of HIFU treatment for lower face rejuvenation.

The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

Bioinformatic analysis of proteomic data for iron, inflammation, and hypoxic pathways in restless legs syndrome.

OBJECTIVE/BACKGROUND: We performed bioinformatic analysis of proteomic data to identify the biomarkers of restless legs syndrome (RLS) and provide insights into the putative pathomechanisms, including iron deficiency, inflammation, and hypoxic pathways. PATIENTS/METHODS: Patients with drug-naïve idiopathic RLS were recruited at a university hospital from June 2017 to February 2018. Serum samples from patients with RLS (n = 7) and healthy sex- and age-matched controls (n = 6) were evaluated by proteomic analysis. For differentially expressed proteins (DEPs) in patients with RLS, compared to those in controls, the expression profiles and protein-protein interaction (PPI) network were characterized between dysregulated proteins and extracted proteins involved in iron deficiency, hypoxia, and inflammation responses using the String database (http://string-DB.org). The PPI network was visualized by Cytoscape ver. 3. 7. 1. Statistical analyses of the validation Western blot assays were performed using a Student's t-test. RESULTS: Interactome network analysis revealed a relationship among the eight proteins, their associated genes, and 150, 47, and 11 proteins related to iron deficiency, inflammation, and hypoxic pathways, respectively. All DEPs were well associated with inflammation, and complement 3, complement C4A, alpha-2 HS glycoprotein, and alpha-2 macroglobulin precursor were found to be in hub positions of networks involved in PPIs including iron deficiency, hypoxia pathway, and inflammation. C3 and C4A were verified using western blotting. CONCLUSIONS: We identified key molecules that represent the selected cellular pathways as protein biomarkers by PPI network analysis. Changes in inflammation can mediate or affect the pathomechanism of RLS and can thus act as systemic biomarkers.

Resveratrol Inhibits Particulate Matter-Induced Inflammatory Responses in Human Keratinocytes.

Particulate matter (PM), a major air pollutant, is a complex mixture of solid and liquid particles of various sizes. PM has been demonstrated to cause intracellular inflammation in human keratinocytes, and is associated with various skin disorders, including atopic dermatitis, eczema, and skin aging. Resveratrol is a natural polyphenol with strong antioxidant properties, and its beneficial effects against skin changes due to PM remain elusive. Therefore, in the present study, we investigated the effect of resveratrol on PM-induced skin inflammation and attempted to deduce the molecular mechanisms underlying resveratrol's effects. We found that resveratrol inhibited PM-induced aryl hydrocarbon receptor activation and reactive oxygen species formation in keratinocytes. It also suppressed the subsequent cellular inflammatory response by inhibiting mitogen-activated protein kinase activation. Consequentially, resveratrol reduced PM-induced cyclooxygenase-2/prostaglandin E2 and proinflammatory cytokine expression, including that of matrix metalloproteinase (MMP)-1, MMP-9, and interleukin-8, all of which are known to be central mediators of various inflammatory conditions and aging. In conclusion, resveratrol inhibits the PM-induced inflammatory response in human keratinocytes, and we suggest that resveratrol may have potential for preventing air pollution-related skin problems.

Time-Dependent Risk of Acute Myocardial Infarction in Patients With Alopecia Areata in Korea.

Importance: Alopecia areata (AA) is a common autoimmune disease presenting as nonscarring hair loss. Although AA can be associated with other autoimmune comorbidities or atopic diseases, little is known about the risk of cardiovascular diseases in patients with AA. Objective: To investigate the risk of acute myocardial infarction (AMI) and cardiovascular risk profiles (CVRPs) in patients with AA via a large-scale epidemiologic study. Design, Setting, and Participants: This was a retrospective cohort study using data from the Korean National Health Insurance claims database, including data from the National Health Screening Program. Patients aged 30 to 89 years who were newly diagnosed with AA between January 1, 2006, and December 31, 2017, and controls without AA matched by age and sex were enrolled. Data were analyzed between July 2018 and August 2019. Exposures: Presence of AA. Main Outcomes and Measures: The CVRPs and incidence rates of AMI were assessed in participants with and without AA. The stratified Cox regression hazard model was used to estimate the relative hazards over time. Results: A total of 228 886 patients with AA, ranging in age from 30 to 89 years (mean [SE] age, 44.37 [0.005] years; 127 564 [55.7%] men) and 4 577 720 matched controls without AA were identified. Patients with AA tended to have slightly better CVRPs than controls in all items except smoking status before and after the diagnosis (participants with normal systolic blood pressure who were nonsmokers: 44.6% vs 42.7% and 57.8% vs 61.6% in patients with AA vs controls before and after the diagnosis, respectively). In the early phase of observation, the cumulative incidence of AMI in patients with AA was lower than that in controls (incidence rate ratio of AMI in patients with AA compared with that in controls, 0.52 [95% CI, 0.42-0.65] between 2-4 years); however, during the later phase of the 12-year follow-up period, it increased exponentially and was greater than in the control group (incidence rate ratio, 2.06 [95% CI, 1.71-2.45] between 8-10 years). Similarly, after adjusting for CVRPs, the risk of developing AMI was lower in patients with AA than in controls at the beginning of the observation period (adjusted hazard ratio (HR), 0.17 [95% CI, 0.12-0.25] between 0-2 years); however, by 8 years postdiagnosis, the risk was higher in those with AA (adjusted HR, 1.37 [95% CI, 1.11-1.70] between 8-10 years), and it increased thereafter (adjusted HR, 4.51 [95% CI, 3.65-5.58] between 10-12 years). Conclusions and Relevance: In patients with AA, there was a significantly increased risk of AMI over time during the 12-year follow-up period independent of CVRPs. Close long-term monitoring of cardiovascular health in patients with AA might be appropriate.

A Randomized, Active-Controlled, 52-Week Study of Hyaluronic Acid Fillers for Anteromedial Malar Region Augmentation.

BACKGROUND: Hyaluronic acid (HA) fillers for volume augmentation in the anteromedial malar region of Asians have been popular for many years. However, studies on their long-term effectiveness are lacking. This study aimed to evaluate the effectiveness and safety of HA fillers injected into the anteromedial malar region for volume augmentation for up to 52 weeks. METHODS: Each anteromedial malar region of the subjects was treated with YVOIRE Contour (YVOC) in one side and Restylane Sub-Q (RESS) in the other and followed up at weeks 2, 14, 26, and 52. The volume using the mid-face aesthetic scale (MFAS) ranging from 0 (full) to 4 (very severely sunken) and the subject's satisfaction and adverse events were evaluated. RESULTS: Total 83 subjects were randomized and treated with YVOC and RESS. The LS means (standard error) of MFAS score in the YVOC and RESS groups were both 2.56 (0.05) at baseline, 1.32 (0.07) and 1.39 (0.07) at week 26, and 1.84 (0.10) and 1.89 (0.10) at week 52, respectively. The difference in the LS mean of MFAS score between the groups at week 26 was 0.07 (95% confidence interval, 0.01-0.12), showing the non-inferiority of YVOC to RESS. About 70% of subjects were still satisfied with the results at week 52. No specific safety concern was detected. CONCLUSIONS: The HA fillers injected for the anteromedial malar augmentation maintained the volume well for up to 52 weeks. Additionally, both YVOC and RESS show similar effectiveness and safety profiles.

Reconstruction of nasal supratip defect using vertical alar groove tissue.

Background: Several local flaps have been introduced for the reconstruction of small-to-medium-sized nasal supratip defects.Objective: To evaluate the outcome of reconstructing supratip defects using tangential advancement flaps from the vertical alar groove tissue.Methods and materials: Medical records of 20 patients who underwent supratip reconstruction using this flap between January 2012 and July 2018 were retrospectively analyzed. The postoperative photographs were assessed by three dermatologists using a four-scale investigator's global assessment.Results: The male-to-female ratio was 9:11, with a mean age of 72.6 years (range, 56-89 years). In all 20 cases, defects were caused by a wide local excision of non-melanoma skin cancer on the nose. The mean diameter of the defects was 1.20 cm (ranging from 0.5 to 1.9 cm). The mean follow-up period was 14.0 months (ranging from 0.5 to 48 months). Excellent or good surgical outcome was reported in 95% of patients.Conclusions: Creating a tangential advancement flap using the vertical alar groove tissue is a simple, single-stage procedure with excellent surgical outcome. It may be useful in the reconstruction of supratip defects with a diameter of less than 2 cm.

The HER2 S310F Mutant Can Form an Active Heterodimer with the EGFR, Which Can Be Inhibited by Cetuximab but Not by Trastuzumab as well as Pertuzumab.

G309 or S310 mutations on the HER2 extracellular domain II induce receptor activation. Clinically, S310F is most frequent among HER2 extracellular domain mutations and patients with the S310F mutation without HER2 amplification responded to trastuzumab with or without the pertuzumab combination. However, the ability of S310F mutant to form homodimers or heterodimers with wild-type HER2 and other HER receptors, or their reactivity to trastuzumab and pertuzumab treatments, has not been reported. We overexpressed S310F as well as G309A, G309E and S310Y HER2 mutants and tested their reactivity to trastuzumab and pertuzumab. All mutants reacted to trastuzumab, but S310F mutant did not react to pertuzumab along with S310Y or G309E mutants. Thereafter, we tested the effects of trastuzumab and pertuzumab on 5637 cell line expressing both wild-type HER2 and S310F mutant. The ligand-independent HER2 homodimerization blocking antibody, trastuzumab, did not inhibit the activation of the HER2 receptor, suggesting that the S310F HER2 mutant did not form homodimers or heterodimers with wild-type HER2. Because 5637 cells overexpressed the EGFR, the effects of cetuximab and gefitinib were determined, and both inhibited the activation of HER2 and significantly reduced cell growth. Because pertuzumab did not inhibit the phosphorylation of HER2 while it bound to wild-type HER2, EGFR-mediated phosphorylation is expected to occur on the S310F mutant. To confirm whether the S310F mutant HER2 retained its affinity to the EGFR, single molecule interaction analyses using TIRF microscopy were performed, which showed that S310F mutant successfully formed complexes with EGFR. In conclusion, HER2 S310F mutant can form an active heterodimer with the EGFR and it can be inhibited by cetuximab, but not by trastuzumab in combination with pertuzumab.