Highly potent anti-melanogenic effect of 2-thiobenzothiazole derivatives through nanomolar tyrosinase activity inhibition.

Compounds with sulfhydryl substituents and azole compounds exhibit potent anti-tyrosinase potency. 2-Thiobenzothiazole (2-TBT), a hybrid structure of sulfhydryl and azole, exists in two tautomeric forms, with the thione form being predominant according to several studies. 2-TBT derivatives were synthesized as potential tyrosinase inhibitors as the thione tautomeric form has the same N-CS moiety as phenylthiourea (PTU), which is suitable for chelation with the copper ions present in the tyrosinase active site. Eight of the ten 2-TBT derivatives inhibited the monophenolase and diphenolase activities of mushroom tyrosinase, with IC50 values of 0.02-0.83 µM. Kinetic studies and molecular dynamics simulations were performed to determine their mode of action and confirm that the 2-TBT derivatives bind to the tyrosinase active site with high stability. Derivatives 3, 4, 8, and 10 strongly inhibited melanogenesis in B16F10 cells in a pattern similar to the results of cellular tyrosinase inhibition, thereby suggesting that their ability to inhibit melanogenesis was due to their tyrosinase inhibitory activity. In a depigmentation experiment using zebrafish embryos, all 2-TBT derivatives showed better potency than kojic acid, even at 400 to 2000 times lower concentration, and 1 and 10 reduced zebrafish larva pigmentation more strongly than PTU even at 20 times lower concentration. Experiments investigating the changes in tyrosinase inhibitory activity of 2-TBT derivatives in the presence and absence of CuSO4 and their copper chelating ability supported that these derivatives exert their anti-melanogenic effect by chelating the copper ions of tyrosinase. These results suggest that 2-TBT derivatives are promising candidates for the treatment of hyperpigmentation-related disorders.

Targeting pyruvate dehydrogenase kinase 1 overcomes EGFR C797S mutation-driven osimertinib resistance in non-small cell lung cancer.

Osimertinib, a selective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), effectively targets the EGFR T790M mutant in non-small cell lung cancer (NSCLC). However, the newly identified EGFR C797S mutation confers resistance to osimertinib. In this study, we explored the role of pyruvate dehydrogenase kinase 1 (PDK1) in osimertinib resistance. Patients exhibiting osimertinib resistance initially displayed elevated PDK1 expression. Osimertinib-resistant cell lines with the EGFR C797S mutation were established using A549, NCI-H292, PC-9, and NCI-H1975 NSCLC cells for both in vitro and in vivo investigations. These EGFR C797S mutant cells exhibited heightened phosphorylation of EGFR, leading to the activation of downstream oncogenic pathways. The EGFR C797S mutation appeared to increase PDK1-driven glycolysis through the EGFR/AKT/HIF-1α axis. Combining osimertinib with the PDK1 inhibitor leelamine helped successfully overcome osimertinib resistance in allograft models. CRISPR-mediated PDK1 knockout effectively inhibited tumor formation in xenograft models. Our study established a clear link between the EGFR C797S mutation and elevated PDK1 expression, opening new avenues for the discovery of targeted therapies and improving our understanding of the roles of EGFR mutations in cancer progression.

Thiazol-4(5H)-one analogs as potent tyrosinase inhibitors: Synthesis, tyrosinase inhibition, antimelanogenic effect, antioxidant activity, and in silico docking simulation.

As the ß-phenyl-α,ß-unsaturated carbonyl (PUSC) structure was previously identified to play a key role in tyrosinase inhibition, 14 analogs with a PUSC structure built on a thiazol-4(5H)-one scaffold were synthesized using Knoevenagel condensation to serve as potential tyrosinase inhibitors. Through mushroom tyrosinase inhibition experiments, two analogs 9 and 11 were identified as potent tyrosinase inhibitors, with 11 exhibiting an IC50 value of 0.4 ± 0.01 µM, which indicates its 26-fold greater potency than kojic acid. Kinetic studies using Lineweaver-Burk plots revealed that 9 and 11 are competitive and mixed-type inhibitors, respectively; these kinetic results were supported by docking simulations. According to the B16F10 cell-based experiments, 9 and 11 inhibited melanogenesis more effectively than kojic acid due to their potent cellular tyrosinase inhibitory activity. In addition, analogs 9 and 11 exhibited moderate-to-strong antioxidant capacity, scavenging ABTS+, DPPH, and ROS radicals. In particular, analog 12 with a catechol moiety exhibited very strong ROS-scavenging activity, similar to Trolox. These results suggest that analogs 9 and 11, which exhibit potent tyrosinase inhibitory activity in mushroom and mammalian cells and anti-melanogenic effects in B16F10 cells, are promising antibrowning agents for crops and skin lightening agents for hyperpigmentation-related diseases.

Frankincense ameliorates endometriosis via inducing apoptosis and reducing adhesion.

Background: Frankincense, a resin derived from trees of the Boswellia genus, has been used as an incense and a type of herbal medicine for treating inflammatory diseases such arthritis, chronic bowel illness, and asthma. While endometriosis is a well-known inflammatory gynecological illness caused by the ectopic attachment and development of uterine tissue over the menstrual cycle, the impact of frankincense on this illness is poorly understood. The purpose of this study was to explore the effects of frankincense on endometriosis. Methods: We used a network pharmacological assessment, in vitro and in vivo investigations with a human endometriotic cell line as well as a syngeneic uterine transfer mouse model. High-performance liquid chromatographic analysis was used to compare water-extracted frankincense (Fr) to its reference compounds and validate the sample. Results: A network pharmacological analysis suggested a positive effect of Fr on endometriosis. Fr relieved endometriosis by reducing ectopic endometrial adherence and development, according to both in vivo and in vitro models. We suggested that the ER stress/p53-apoptosis and chemokine-migration/adhesion pathways underlie Fr's anti-endometriotic action using RNA sequencing and bioinformatic analysis. Conclusion: This study revealed the potential effect of Fr on endometriosis using an experimental investigation. Fr may have the potential to be an effective and safe treatment for endometriosis.

Anti-tyrosinase flavone derivatives and their anti-melanogenic activities: Importance of the ß-phenyl-α,ß-unsaturated carbonyl scaffold.

Flavone derivatives were designed and synthesized based on the hypothesis that flavones containing the ß-phenyl-α,ß-unsaturated carbonyl (PUSC) scaffold have potential anti-tyrosinase activity. Flavones 1a and 1e inhibited mushroom tyrosinase more potently than kojic acid, and 1e inhibited monophenolase and diphenolase 61- and 28-fold more than kojic acid, respectively. Kinetic studies on mushroom tyrosinase indicated that 1a and 1e competitively inhibit monophenolase and diphenolase, and docking results supported these results. In an in vitro assay using B16F10 murine cells, 1a and 1e inhibited melanin production more potently than kojic acid, and this was attributed to the inhibition of tyrosinase. Furthermore, 1a and 1e strongly scavenged DPPH and ABTS radicals and ROS, which suggested that their antioxidant properties were at least partly responsible for their anti-melanogenic effects. Moreover, flavone 1a also inhibited the gene expressions of the melanogenesis-related genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. Our findings that flavone derivatives (i) directly inhibit tyrosinase, (ii) act as antioxidants, and (iii) inhibit the expressions of melanogenesis-related genes suggest their potential use as natural melanogenesis inhibitors. Furthermore, the study confirms that the PUSC scaffold confers anti-tyrosinase activity.

Acquired susceptibility to autoimmune diseases in pediatric patients with Escherichia coli infection: A population-matched retrospective cohort study.

BACKGROUND: Escherichia coli (E.coli) infection has been proposed to play an important role as an initial trigger in the development of autoimmunity via molecular mimicry. However, there has been no preliminary cohort study to establish the association of E.coli infection with autoimmune diseases. Therefore, we conducted a large scale, population-matched cohort study to determine the risk of autoimmune disease among patients with exposure to E.coli. METHODS: Utilizing the National Health Insurance Service database, we retrospectively analyzed a total of 259,875 Korean children that consisted of 23,625 exposed and 236,250 unexposed persons from January 1, 2002 to December 31, 2017. The exposed cohort was defined as patients diagnosed with E.coli infection. Unexposed controls were matched by birth year and sex at a 1:10 ratio for each exposed patient, using incidence density sampling. The primary outcome was autoimmune disease development. We used the Cox model to estimate the risks of autoimmune diseases among patients diagnosed with E.coli infection. RESULTS: Over a mean follow-up of 10 years, there were 1455 autoimmune disease cases among exposed patients (incidence rate, 63.6 per 10,000 person-years) and 11,646 autoimmune disease cases among unexposed persons (incidence rate, 50.4 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.254 (95% CI 1.187-1.325). E.coli infection was associated with increased risks of autoimmune diseases; Reactive arthritis, HR 1.487, 95% CI 1.131-1.956; Henoch Schönlein purpura, HR 1.265, 95% CI 1.050-1.524; Systemic lupus erythematosus, HR 1.838, 95% CI 1.165-2.898; Sjögren's syndrome, HR 2.002, 95% CI 1.342-2.987; IgA nephropathy, HR 1.613, 95% CI 1.388-1.874. Kaplan-Meier cumulative incidence curves also showed a significant association between E.coli infection and incident autoimmune disease (p < 0.0001). This relationship was not only independent of demographic variables, but also remained consistent across various sensitivity analyses. On the other hand, patients with longer hospital stay for E.coli infection were at a higher risk of autoimmune disease (p = 0.0003), and the risk of autoimmune disease also tended to increase, as the frequency of E.coli infection was higher. Moreover, the relative risk of autoimmune disease seemed to be attenuated by use of antibiotics and a history of intestinal infectious disease, but elevated by coexistence of other autoimmune diseases. CONCLUSIONS: Our cohort study indicates that E.coli infection was significantly associated with increased susceptibility to autoimmune diseases, even after adjusting for different factors. Thus, among environmental factors, a previous history of E.coli infection could be a predisposing risk factor in the development of autoimmune diseases.

Coordination Changes in Densified Aluminate Glass upon Compression up to 65 GPa: A View from Solid-State Nuclear Magnetic Resonance.

Deciphering the structural evolution in irreversibly densified oxide glasses is crucial for fabricating functional glasses with tunable properties and elucidating the nature of pressure-induced anomalous plastic deformation in glasses. High-resolution NMR spectroscopy quantifies atomic-level structural information on densified glasses; however, its application is limited to the low-pressure range due to technical challenges. Here, we report the first high-resolution NMR spectra of oxide glass compressed by diamond anvil cells at room temperature, extending the pressure record of such studies from 24 to 65 GPa. The results constrain the densification path through coordination transformation of Al cations. Based on a statistical thermodynamic model, the stepwise changes in the Al fractions of oxide glasses and the effects of network polymerization on the densification paths are quantified. These results extend the knowledge on densification of the previously unattainable pressure conditions and contribute to understanding the origin of mechanical strengthening of the glasses.

Factors affecting good prognosis for out-of-hospital cardiac arrest patients in interhospital helicopter transport in rural area

Objective@#Out-of-hospital cardiac arrest (OHCA) is a common cause of death and serious neurological morbidity. Efforts to reduce the mortality due to OHCA focus on the “chain of survival.” The survival rates of OHCA patients are known to be related to prehospital conditions. @*Methods@#Helicopter emergency medical services (HEMS) provide a variety of procedures, such as cardiopulmonary resuscitation (CPR) and other advanced interventions that may improve the prognosis of OHCA patients. HEMS can respond quickly to long-distance or difficult-to-access places. This study attempted to investigate the characteristics of OHCA patients who had utilized inter-hospital air transport. The study was an observational cohort study using prospective data from a single suburban tertiary care hospital over a period of 7 years. The study data were analyzed using the SPSS version 28 software. @*Results@#In the survival group, the cause was more cardiac-related than in the death group (54% vs. 23.4%; P<0.001). CPR by bystanders and defibrillation by the emergency medical technicians were more frequent than in the death group. Also, the initial rhythm of the survivors was mainly VT or VF (48.0% vs. 14.9%; P<0.003). @*Conclusion@#In the HEMS mission with OHCA arrest, the patients with a cardiac origin, witnessed arrest, those with a shockable rhythm and shorter CPR time had a trend towards better survival and neurological outcomes in this study.

Recovery from Upper Eyelid Sulcus Deepening Following Switch from Prostaglandin Analogues to EP2 Receptor Agonist

Purpose@#To report a case of recovery from deepening of the upper eyelid sulcus after switching from prostaglandin FP receptor agonists to an EP2 receptor agonist.Case summary: A 65-year-old male patient with suspicion of glaucoma presented for detailed examinations. At the initial visit, his best-corrected visual acuity was 1.0 in both eyes, and the intraocular pressure (IOP) was 14/14 mmHg. Examination revealed no specific findings in the anterior segment, mild early cataracts bilaterally, and moderate glaucomatous changes. Therefore, bimatoprost/timolol fixed-combination eye drops were administered in both eyes. After 1 month, the IOP was 11/11 mmHg and no evidence of glaucoma progression was found. After 10 months, the IOP was 17/18 mmHg and there was deepening of the upper eyelid sulcus bilaterally. Consequently, bimatoprost/timolol fixed combination eye drops were switched to omidenepag isopropyl. Within 2 months of the switch, the deepening of the upper eyelid sulcus recovered completely and the IOP was 14/13 mmHg. @*Conclusions@#Patients with prostaglandin-associated periorbitopathy should be switched to non-prostaglandin drugs or EP2 receptor agonists. Our patient exhibited complete recovery of the upper eyelid sulcus deepening after switching to an EP2 agonist.

Effects of a Proton-Pump Inhibitor on Postnasal Drip Symptoms in Patients With Laryngopharyngeal Reflux

Background and Objectives@#Laryngopharyngeal reflux (LPR) is an increasingly common disease, characterized by stomach acid reflux reaching the upper airways. Postnasal drip (PND) is a known consequence of LPR, defined as mucus accumulation perceived in the posterior areas of the nose and throat. PND is among the most common causes of persistent cough, hoarseness, sore throat, and other symptoms, affecting the quality of life. This study aimed to evaluate the effects of a proton-pump inhibitor (PPI) on PND symptoms in patients with LPR. @*Methods@#We prospectively enrolled patients diagnosed with LPR at our institution between September 2019 and June 2020. The patients were randomly assigned to either the treatment group (20 mg of ilaprazole daily for 8 weeks) or the control group. The scores for the Reflux Symptom Index (RSI), Reflux Finding Score (RFS), and Sino-Nasal Outcome Test (SNOT)-20 were evaluated at baseline and at the end of treatment, focusing on PND symptoms. @*Results@#Eighty patients (28 men and 52 women; mean age, 48.8 years, range, 22–78 years) were enrolled, with 43 in the treatment group and 37 in the control group. The initial RSI, RFS, and SNOT-20 scores were similar between the two groups, and they decreased significantly only in the treatment group (p=0.002, p<0.001, and p=0.015, respectively). However, the PND symptom scores showed a significant decrease in the treatment group only in the RSI (p=0.012). @*Conclusion@#PPI treatment for 8 weeks may be effective in improving PND symptoms in patients with LPR.

Diagnostic proficiency test using digital cytopathology and comparative assessment of whole slide images of cytologic samples for quality assurance program in Korea

Background@#The Korean Society for Cytopathology introduced a digital proficiency test (PT) in 2021. However, many doubtful opinions remain on whether digitally scanned images can satisfactorily present subtle differences in the nuclear features and chromatin patterns of cytological samples. @*Methods@#We prepared 30 whole-slide images (WSIs) from the conventional PT archive by a selection process for digital PT. Digital and conventional PT were performed in parallel for volunteer institutes, and the results were compared using feedback. To assess the quality of cytological assessment WSIs, 12 slides were collected and scanned using five different scanners, with four cytopathologists evaluating image quality through a questionnaire. @*Results@#Among the 215 institutes, 108 and 107 participated in glass and digital PT, respectively. No significant difference was noted in category C (major discordance), although the number of discordant cases was slightly higher in the digital PT group. Leica, 3DHistech Pannoramic 250 Flash, and Hamamatsu NanoZoomer 360 systems showed comparable results in terms of image quality, feature presentation, and error rates for most cytological samples. Overall satisfaction was observed with the general convenience and image quality of digital PT. @*Conclusions@#As three-dimensional clusters are common and nuclear/chromatin features are critical for cytological interpretation, careful selection of scanners and optimal conditions are mandatory for the successful establishment of digital quality assurance programs in cytology.

Usefulness of a new polyvinyl alcohol hydrogel (PVA-H)-based simulator for endoscopic submucosal dissection training: a pilot study

Background/Aims@#We developed a new endoscopic submucosal dissection (ESD) simulator and evaluated its efficacy and realism for use training endoscopists. @*Methods@#An ESD simulator was constructed using polyvinyl alcohol hydrogel sheets and compared to a previous ESD simulator. Between March 1, 2020, and December 30, 2021, eight expert endoscopists from three different centers analyzed the procedure-related factors of the simulator. Five trainees performed gastric ESD exercises under the guidance of these experts. @*Results@#Although the two ESD simulators provided overall favorable outcomes in terms of ESD-related factors, the new simulator had several benefits, including better marking of the target lesion’s limits (p<0.001) and overall handling (p<0.001). Trainees tested the usefulness of the new ESD simulator. The complete resection rate improved after 3 ESD training sessions (9 procedures), and the perforation rate decreased after 4 sessions (12 procedures). @*Conclusions@#We have developed a new ESD simulator that can help beginners achieve a high level of technical experience before performing real-time ESD procedures in patients.

Effects of Particulate Matter on Allergic Rhinitis and Possible Mechanisms / 대한이비인후과학회지

Health impacts of particulate matter (PM) have become a global concern. PM tends to affect patients with allergic diseases, such as allergic rhinitis (AR), more severely. Many epidemiological studies have shown that PM increases outpatient clinic visits as well as the prevalence and severity of AR, while decreasing the quality of life of AR patients. However, the exact mechanisms underlying the effects of PM on the development and exacerbation of AR are still poorly understood. Various mechanisms are involved in the effects of PM on AR, including immunological response, oxidative stress, epithelial barrier dysfunction, allergic sensitization, and epigenetic modification. This article reviews epidemiological and clinical studies on the effects of PM on AR, and the mechanisms by which PM aggravates AR.

Effects of Atomoxetine for the Treatment of Neurogenic Orthostatic Hypotension in Patients With Alpha-synucleinopathies: A Systematic Review of Randomized Controlled Trials and a Focus-Group Discussion

Background@#and PurposeNeurogenic orthostatic hypotension (nOH) is one of the most important nonmotor symptoms in patients with α-synucleinopathies. Atomoxetine is a selective norepinephrine transporter blocker that is a treatment option for nOH. This systematic review and expert focus-group study was designed to obtain evidence from published data and clinical experiences of Korean movement-disorder specialists about the efficacy and safety of atomoxetine for the pharmacological treatment of nOH in patients with α-synucleinopathies. @*Methods@#The study comprised a systematic review and a focus-group discussion with clinicians. For the systematic review, multiple comprehensive databases including MEDLINE, Embase, Cochrane Library, CINAHL, PsycInfo, and KoreaMed were searched to retrieve articles that assessed the outcomes of atomoxetine therapy. A focus-group discussion was additionally performed to solicit opinions from experts with experience in managing nOH. @*Results@#The literature review process yielded only four randomized controlled trials on atomoxetine matching the inclusion criteria. Atomoxetine effectively increased systolic blood pressure and improved OH-related symptoms as monotherapy or in combination with other drugs. Its effects were pronounced in cases with central autonomic failure, including multiple-system atrophy (MSA). Atomoxetine might be a safe monotherapy regarding the risk of supine hypertension. @*Conclusions@#Atomoxetine is an effective and safe option for short-term nOH management, which could be more evident in patients with central autonomic dysfunction such as MSA. However, there is a paucity of evidence in the literature, and data from the focus-group discussion were inadequate, and so further investigation is warranted.

Treatment for subarachnoid hemorrhage due to ruptured posterior cerebral arterial dolichoectasia with aortic arch anomaly

Subarachnoid hemorrhage (SAH) due to ruptured posterior cerebral artery (PCA) intracranial arterial dolichoectasia (IADE) is very rare. As these lesions are difficult to treat microsurgically, neurointervention is preferred because the dolichoectatic artery does not have a clear neck, and the surgical field of view was deep seated with the SAH. However, in some cases, neurointervention is difficult due to anatomical variation of the blood vessel to access the lesion. In this case, a 30-year-old male patient presented with a ruptured PCA IADE and an aortic arch anomaly. Aortic arch anomalies render it difficult to reach the ruptured PCA IADE via endovascular treatment. The orifice of the vertebral artery (VA) was different from the usual cases, so it was difficult to find the entrance. After only finding the VA and arriving at the lesion along the VA, trapping was performed. Herein, we report the PCA IADE with aortic arch anomaly endovascular treatment methods and results.

Relationships between Clinical Status and Gait Parameters in Ankylosing Spondylitis

Background@#This study aimed to identify the relationship between gait parameters and health-related quality of life (HRQOL) in patients with ankylosing spondylitis (AS). @*Methods@#The study group comprised 134 patients with AS and 124 patients were enrolled as controls. All study participants underwent instrumented gait analysis and completed clinical questionnaires. The kinematic parameters of gait were walking speed, step length, cadence, stance phase, single support, double support, phase coordination index (PCI), and gait asymmetry (GA). For each patient, a visual analog scale (VAS; 0–10) score was used to assess back pain, 36-item short form survey (SF-36) questionnaire was administered to evaluate the HRQOL, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was calculated.Using kinematic parameters and questionnaires, statistical analyses were done to investigate significant differences between the groups. Relationship of gait kinematic data and questionnaires of clinical outcome was also evaluated. @*Results@#Among the 134 patients with AS, 34 were women and 100 were men. In the control group, 26 were women and 98 were men. The patients with AS and control group patients had significant differences in terms of walking speed, step length, single support, PCI, and GA. However, such differences were not observed in cadence, stance phase, and double support (p > 0.05). In correlation analyses, gait kinematic parameters and clinical outcomes were significantly related with each other. In multiple regression analysis performed to identify predictive factors for clinical outcome, walking speed was found to predict VAS, and walking speed and step length were found to predict the BASDAI and SF-36 scores. @*Conclusions@#Patients with and without AS had significant differences in the gait parameters. Correlation analysis showed significant correlation between the gait kinematic data and clinical outcomes. In particular, walking speed and step length successfully predicted clinical outcomes in patients with AS.

Picropodophyllotoxin Inhibits Cell Growth and Induces Apoptosis in Gefitinib-Resistant Non-Small Lung Cancer Cells by Dual-Targeting EGFR and MET

Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive muta-tions initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resis-tance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunc-tion, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.

Efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for hepatitis C in Korea: a Phase 3b study

Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.

Two Cases of Linear Lichen Planus Pigmentosus of the Chin in Korean Women Treated by Fractional Lasers and Polydeoxyribonucleotide Injection

Linear lichen planus pigmentosus is a rare subtype of lichen planus pigmentosus that follows Blaschko’s lines, leaving long-standing residual atrophy and pigmentation, especially in dark-skinned populations. Conventional treatments have several limitations regarding the alleviation of pigmentation and atrophy. We report two cases of Korean women with linear lichen planus pigmentosus on their faces who were successfully treated with fractional lasers and intralesional injection of polydeoxyribonucleotide.