Effects of Cudrania tricuspidata and Sargassum fusiforme extracts on hair growth in C57BL/6 mice / 한국실험동물학회지

Background@#Cudrania tricuspidata is a perennial plant, and Sargassum fusiforme is a brown seaweed with numerous potential benefits, including anticancer, anti-inflammatory, and antioxidant activities. However, the efficacies of C. tricuspidata and S. fusiforme on hair growth have not yet been elucidated. Therefore, the present study examined the effects of C. tricuspidata and S. fusiforme extracts on hair growth in C57BL/6 mice. @*Results@#ImageJ demonstrated that drinking and skin application of C. tricuspidata and/or S. fusiforme extracts significantly increased the hair growth rate in the dorsal skin of C57BL/6 mice compared to the control group. Histological analysis confirmed that drinking and skin application of C. tricuspidata and/or S. fusiforme extracts for 21 days significantly increased the length of hair follicles on the dorsal skin of treated C57BL/6 mice compared to that in the control mice. RNA sequencing analysis revealed that hair growth cycle-related factors (anagen factors) such as Catenin Beta 1 (Ctnnb1) and platelet-derived growth factor (Pdgf) were upregulated (> twofold) only by C. tricuspidata extracts, whereas vascular endothelial growth factor (Vegf) and Wnts were upregulated by both C. tricuspidata or S. fusiforme applications in treated mice (compared to the control mice). In addition, oncostatin M (Osm, a catagen-telogen factor) was downregulated (< 0.5 fold) by C. tricuspidata when administered via both skin and drinking mode in treated mice compared to that in control mice. @*Conclusions@#Our results suggest that C. tricuspidata and/or S. fusiforme extracts show potential hair growth efficacy by upregulating anagen factor genes, including β-catenin, Pdgf, Vegf, and Wnts, and downregulating catagen-telogen factor genes, including Osm, in C57BL/6 mice. The findings suggest that C. tricuspidata and/or S. fusiforme extracts are potential drug candidates to treat alopecia.

Survival Rate and Prognostic Factors of 26 Cases of Angiosarcoma and 26 Cases of Kaposi Sarcoma: A Korean Single-Center Experience / 대한피부과학회지

Background@#Angiosarcoma (AS) and Kaposi sarcoma (KS) are rare malignant and borderline malignant vascular tumors that may first present to a dermatologist. There are few Korean studies that particularly focus on their survival due to low incidence. @*Objective@#To investigate the survival and prognostic factors among patients with AS and KS, in addition to their clinical features. @*Methods@#Between 2000∼2021, medical records of 26 AS and 26 KS patients at a single center were analyzed retrospectively. Additionally, we calculated the disease specific survival (DSS) and overall survival (OS) of two diseases. @*Results@#The mean age of patients with AS was 72.9 years and 67.3 years for KS. The most common tumor location was the scalp in patients with AS (80.8%) and the foot (65.4%) in those with KS. In patients with AS, 1-year DSS and OS rates were 36.0% and 34.6%, respectively. Five-year DSS and OS rates were 24.0% and 20.2%, respectively. In patients with KS, the 1-year DSS and OS rates were 96.2% and 84.6%, respectively. The 5-year DSS and OS were 91.6% and 58.0%, respectively. Patients who were older or had larger lesions than average had decreased DSS and OS in AS. Among the patients with KS, immunosuppressed status, including human immunodeficiency virus infection, showed reduced OS. @*Conclusion@#Apart from confirming grave survival of AS and favorable survival of KS, patient’s age and size of lesion affect survival outcomes in patients with AS. Otherwise, immunosuppressed status affects survival outcomes in patients with KS.

Risk Factors for Prevertebral Soft Tissue Swelling Following Single-level Anterior Cervical Spine Surgery

Objective@#: Anterior cervical spine surgery (ACSS) is a common surgical procedure used to treat cervical spinal degenerative diseases. One of the complications associated with ACSS is prevertebral soft tissue swelling (PSTS), which can result in airway obstruction, dysphagia, and other adverse outcomes. This study aims to investigate the correlation between various cervical sagittal parameters and PSTS following single-level ACSS, as well as to identify independent risk factors for PSTS. @*Methods@#: A retrospective study conducted at a single institution. The study population included all patients who underwent single-level ACSS between January 2014 and December 2022. Patients with a history of cervical spine surgery or trauma were excluded from the study. The presence and severity of PSTS was assessed by reviewing pre- and postoperative imaging studies. The potential risk factors for PSTS that were examined include patient age, sex, body mass index, tobacco use, comorbidities, serum albumin levels, operative time, implant type, implanted level, and various cervical spine sagittal parameters. Multivariate linear regression analysis was performed to identify the independent risk factors for PSTS. @*Results@#: A total of 62 consecutive patients who underwent single-level ACSS over a 8-year period at a single institution were enrolled in this study. Only preoperative segmental angle showed positive correlation with PSTS among various cervical spine sagittal parameters (r=0.36, p=0.005). Artificial disc replacement showed a negative correlation with PSTS (β=-0.38, p=0.002), whereas the use of demineralized bone matrix (DBM) had a positive impact on PSTS (β=0.33, p=0.009). We found that male sex, lower preoperative serum albumin, and implantation of upper cervical level (above C5) were independent predictors for PSTS after single-level ACSS (β=1.21; 95% confidence interval [CI], 0.27 to 2.15; p=0.012; β=-1.63; 95% CI, -2.91 to -0.34; p=0.014; β=1.44; 95% CI, 0.38 to 2.49; p=0.008, respectively). @*Conclusion@#: Our study identified male sex, lower preoperative serum albumin levels, and upper cervical level involvement as independent risk factors for PSTS after single-level ACSS. These findings can help clinicians monitor high-risk patients and take preventive measures to reduce complications. Further research with larger sample sizes and prospective designs is needed to validate these findings.

An Incidentally Discovered Primary Hepatic Gastrointestinal Stromal Tumor Treated by Surgical Resection and Adjuvant Imatinib Therapy: A Case Report

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors derived from precursors of the interstitial cells of Cajal that commonly arise from the stomach or small intestine. These tumors usually contain KIT and/or PDGFRA mutations, which encode type III receptor tyrosine kinases. Approximately 10% of GISTs originate from sites other than the gastrointestinal tract, such as the mesentery, urinary bladder, retroperitoneum, pancreas, gallbladder, and liver. These tumors are hypothesized to originate from interstitial Cajal-like cells or undifferentiated pluripotent mesenchymal cells outside the gastrointestinal tract. Primary hepatic GISTs are rare, with most hepatic GISTs being secondary.Here, we report the case of a 69-year-old woman with a rare primary hepatic GIST. The hepatic GIST, measuring 13.5 cm, was incidentally discovered in the right liver lobe and exhibited heterogeneous arterial phase hyperenhancement, washout, diffusion restriction, low signal intensity in the hepatobiliary phase, intratumoral hemorrhage, necrosis, and fluid-fluid levels. Imaging revealed no evidence of extrahepatic primary lesions. GIST was pathologically confirmed via percutaneous biopsy and subsequent surgical resection.Despite adjuvant imatinib therapy, the tumor recurred with peritoneal seeding 15 months postoperatively.

Intraindividual Comparison of MRIs with Extracellular and Hepatobiliary Contrast Agents for the Noninvasive Diagnosis of Hepatocellular Carcinoma Using the Korean Liver Cancer Association–National Cancer Center 2022 Criteria / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The aim of the present study was to evaluate the per-lesion sensitivity and specificity of the Korean Liver Cancer Association–National Cancer Center (KLCA-NCC) 2022 criteria for the noninvasive diagnosis of hepatocellular carcinoma (HCC), with intraindividual comparison of the diagnostic performance of magnetic resonance imaging with extracellular agents (ECA-MRI) and hepatobiliary agents (HBA-MRI). @*Materials and Methods@#Patients at high risk for HCC who were referred to a tertiary academic institution for hepatic lesions with size ≥ 10 mm between July 2019 and June 2022 were enrolled. A total of 91 patients (mean age, 58.1 years; 76 men and 15 women) with 118 lesions who underwent both ECA-MRI and HBA-MRI were eligible for final analysis. The per-lesion sensitivities and specificities of the KLCA-NCC 2022 criteria using ECA-MRI and HBA-MRI were compared using McNemar’s test. @*Results@#The 118 lesions were 93 HCCs, 4 non-HCC malignancies, and 21 benign lesions. On HBA-MRI, the “definite” HCC category showed significantly higher sensitivity than ECA-MRI (78.5% vs. 58.1%, p 0.999). For “probable” or “definite” HCC categories, there were no differences in the sensitivity (84.9% vs. 84.9%, p > 0.999) and specificity (84.0% vs. 84.0%, p > 0.999) between ECA-MRI and HBA-MRI. @*Conclusion@#The “definite” HCC category of the KLCA-NCC 2022 criteria showed higher sensitivity in diagnosing HCC on HBA-MRI compared with ECA-MRI, without compromising specificity. There were no significant differences in the sensitivity and specificity of “probable” or “definite” HCC categories according to ECA-MRI and HBA-MRI.

Radiologic Assessment of Lung Edema Score as a Predictor of Clinical Outcome in Children with Acute Respiratory Distress Syndrome

Purpose@#The radiographic assessment of lung edema (RALE) score enables objective quantification of lung edema and is a valuable prognostic marker of adult acute respiratory distress syndrome (ARDS). We aimed to evaluate the validity of RALE score in children with ARDS. @*Materials and Methods@#The RALE score was measured for its reliability and correlation to other ARDS severity indices. ARDSspecific mortality was defined as death from severe pulmonary dysfunction or the need for extracorporeal membrane oxygenation therapy. The C-index of the RALE score and other ARDS severity indices were compared via survival analyses. @*Results@#Among 296 children with ARDS, 88 did not survive, and there were 70 ARDS-specific non-survivors. The RALE score showed good reliability with an intraclass correlation coefficient of 0.809 [95% confidence interval (CI), 0.760–0.848]. In univariable analysis, the RALE score had a hazard ratio (HR) of 1.19 (95% CI, 1.18–3.11), and the significance was maintained in multivariable analysis adjusting with age, ARDS etiology, and comorbidity, with an HR of 1.77 (95% CI, 1.05–2.91). The RALE score was a good predictor of ARDS-specific mortality, with a C-index of 0.607 (95% CI, 0.519–0.695). @*Conclusion@#The RALE score is a reliable measure for ARDS severity and a useful prognostic marker of mortality in children, especially for ARDS-specific mortality. This score provides information that clinicians can use to decide the proper time of aggressive therapy targeting severe lung injury and to appropriately manage the fluid balance of children with ARDS.

The Clinical Features and Risk Factors of Subglottic Cysts in Children: A Clinical Experience Using the Spontaneous Respiration Technique

Objectives@#. Subglottic cysts (SGCs) are a rare cause of respiratory distress resulting from upper airway obstruction in infants and young children. Risk factors other than prematurity with a history of endotracheal intubation have not yet been well elucidated. Therefore, we aimed to describe the clinical features and analyze the risk factors of SGCs. @*Methods@#. We conducted a retrospective review of medical records of pediatric patients who underwent marsupialization for SGCs between January 2017 and March 2022. These records were then compared with those of controls with a history of neonatal intubation, with a case-to-control ratio of 1:3. @*Results@#. Eleven patients (eight boys and three girls) diagnosed with SGCs and 33 control patients (26 boys and seven girls) were included. All patients had a history of premature birth and neonatal intubation. Symptoms of SGCs appeared at a mean age of 8.2 months (range, 1–14 months) after extubation. The mean duration of intubation was 21.5 days (range, 2–90 days), and the intubation period was longer in patients with SGCs than in controls (21.5±24.8 days vs. 5.3±7.1 days; P<0.001). Furthermore, gestational age (28.3±4.2 weeks vs. 33.8±4.4 weeks; P=0.001) and birth weight (1,134.1±515.1 g vs. 2,178.2±910.1 g; P=0.001) were significantly lower in patients with SGCs than in controls. Multivariable analysis identified the intubation period as an independent risk factor. @*Conclusion@#. This study showed that gestational age, birth weight, and the intubation period were significantly associated with the development of SGCs. Pediatric patients presenting with progressive dyspnea who have the corresponding risk factors should undergo early laryngoscopy for the differential diagnosis of SGC.

A Case of Multiple Necrotic Dyskeratotic Cells within the Upper Epidermis and Horny Layer Revealing Persistent Papules and Plaques of Adult-Onset Still’s Disease

It is important to differentiate violaceous to dusky red papules and plaques that widely persist on the trunk and extremities because there are dermatoses that could be fatal, such as lupus erythematosus, dermatomyositis, drug eruptions, and graft-versus-host disease.Dyskeratotic cells only in the upper epidermis and horny layer are not well known, but it is a distinctive histopathological pattern of atypical type of rash of adult-onset Still’s disease (AOSD). AOSD rash is a transient salmon-colored rash that occurs and disappears with fever; however, an atypical type of rash called “persistent dermal plaque” or “persistent pruritic eruptions” has also been reported. It occurs and persists even after fever subsides.Herein, we describe a case with necrotic dyskeratotic cells in the upper epidermis and horny layer without AOSD symptoms lasting for five years.

A Case of Lymphomatoid Papulosis, Type F / 대한피부과학회지

Lymphomatoid papulosis (LyP) is a relatively uncommon CD30＋ lymphoproliferative disorder with a good prognosis. However, it is important to be cautious because 4%∼25% of the cases are accompanied by secondary lymphoma. LyP is divided into subtypes of infiltrate-descriptive categories based on the histological findings. Classically, LyP shows a patchy, wedge-shaped, dermal infiltrate of small to intermediate-sized lymphocytes, with atypical lymphoid cells and a variable mixture of neutrophils, histiocytes, and eosinophils. Follicular LyP (type F LyP), which was recently described and is not yet included as an official subtype in the World Health Organization classification, shares these characteristics, although its infiltrate is folliculocentric. Variable folliculotropism, follicular dilation, rupture, and mucinosis can occur. This entity is commonly misdiagnosed and is possibly underreported because its histopathologic features can masquerade as more common follicular-based entities. Herein, we report the case of follicular type LyP, which has not been reported in in Korean dermatology literature.

De Novo Crescentic Glomerulonephritis Following COVID-19 Infection:A Pediatric Case Report

As the global coronavirus disease 2019 (COVID-19) pandemic continues to sweep across the globe, reports of kidney involvement in adult patients infected with COVID-19 have been documented, and recently, cases in the pediatric population have also been reported.This report highlights the case of an 11-year-old boy who developed acute kidney injury presenting as gross hematuria, proteinuria, and hypertension immediately after a COVID-19 infection. A renal biopsy allowed us to diagnose the patient with post-COVID-19 infectionassociated de novo crescentic immune-mediated glomerulonephritis. Oral prednisolone and cyclophosphamide treatments were initiated after methylprednisolone pulse therapy administration. Currently, the patient is receiving medical treatment for five weeks, and his renal function is gradually recovering. Previous studies have suggested that, although quite rare, a variety of kidney complications can occur after COVID-19 infection or vaccination, and it is recommended to monitor renal function through evaluation. Herein, we report a pediatric case of post-COVID-19 infection-associated de novo crescentic immune-mediated glomerulonephritis consistent with rapidly progressive glomerulonephritis.

Association between Inhaled Corticosteroid Use and SARS-CoV-2 Infection: A Nationwide Population-Based Study in South Korea / 결핵및호흡기질환

Background@#Although it is known that inhaled corticosteroid (ICS) use may increase the risk of respiratory infection, its influence on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Thus, the aim of this study was to investigate the association between ICS use and the positivity of SARS-CoV-2 infection among patients with chronic respiratory diseases. @*Methods@#Nationwide data of 44,968 individuals with chronic respiratory diseases tested for SARS-CoV-2 until May 15, 2021 were obtained from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea. The positivity of SARS-CoV-2 infection was retrospectively analysed according to the prescription, type, and dose of ICS taken one year before SARS-CoV-2 test. @*Results@#Among 44,968 individuals tested, 931 (2.1%) were positive for SARS-CoV-2. A total of 7,019 patients (15.6%) were prescribed ICS one year prior to being tested for SARS-CoV-2. Low, medium, and high doses of ICS were prescribed in 7.5%, 1.6%, and 6.5% of total cases, respectively. Among types of ICS, budesonide, fluticasone, beclomethasone, and ciclesonide were prescribed in 3.7%, 8.9%, 2.3%, and 0.6% of total cases, respectively. A multivariate analysis showed no significant increase in infection with ICS use (odds ratio, 0.84; 95% confidence interval, 0.66–1.03). Moreover, there were no associations between the positivity of infection and the dose or type of ICS prescribed. @*Conclusion@#Prior ICS use did not increase the positivity for SARS-CoV-2 infection. Moreover, different doses or types of ICS did not affect this positivity.

Dermatofibrosarcoma Protuberans with Diversely Atypical Clinical Presentation:Three Case Reports / 대한피부과학회지

Dermatofibrosarcoma protuberans (DFSP) is a relatively rare, slow-growing dermal spindle cell tumor characterized by high local recurrence rates and a low risk of metastasis. It starts as an erythematous indurated papule or plaque where firm nodules subsequently arise, forming typical ‘protuberant’ morphology. However, atypical DFSP presentations, which are difficult to diagnose clinically, have been reported. In this study, we describe three patients diagnosed with diversely atypical DFSP, which were pigmented, hemangioma-like, and cystic DFSP variants. Among them, two patients were misdiagnosed with other diseases, resulting in delayed treatment, with much larger resections needed to achieve local control or avoid recurrence. Therefore, dermatologists should pay attention to these diverse clinical variants of DFSP.

Anti-adipogenic effect of the flavonoids through the activation of AMPK in palmitate (PA)-treated HepG2 cells

Objectives@#The present study observed the anti-adipogenic effects of five major citrus flavonoids, including hesperidin (HES), narirutin (NAR), nobiletin (NOB), sinensetin (SIN), and tangeretin (TAN), on AMP-activated protein kinase (AMPK) activation in palmitate (PA)-treated HepG2 cells. @*Methods@#The intracellular lipid accumulation and triglyceride (TG) contents were quantified by Oil-red O staining and TG assay, respectively. The glucose uptake was assessed using 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG) assay. The levels of AMPK, acetyl-CoA carboxylase (ACC), and glycogen synthase kinase 3 beta (GSK3β) phosphorylation, and levels of sterol regulatory element-binding protein 2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) expression were analyzed by Western blot analysis. The potential interaction between the flavonoids and the γ-subunit of AMPK was investigated by molecular docking analysis. @*Results@#The flavonoid treatment reduced both intracellular lipid accumulation and TG content in PA-treated HepG2 cells significantly. In addition, the flavonoids showed increased 2-NBDG uptake in an insulin-independent manner in PA-treated HepG2 cells. The flavonoids increased the AMPK, ACC, and GSK3β phosphorylation levels and decreased the SREBP-2 and HMGCR expression levels in PA-treated HepG2 cells. Molecular docking analysis showed that the flavonoids bind to the CBS domains in the regulatory γ-subunit of AMPK with high binding affinities and could serve as potential AMPK activators. @*Conclusion@#The overall results suggest that the anti-adipogenic effect of flavonoids on PAtreated HepG2 cells results from the activation of AMPK by flavonoids.

Clinical Implication of Candida Score in Multidrug-Resistant Pneumonia with Airway Candida Colonization / 감염과화학요법

Background@#The growth of Candida in respiratory secretions is usually considered colonization, and antifungal therapy is rarely required. The role of Candida colonization in the progression of bacterial pneumonia remains controversial. The aim of this study was to identify the clinical implication of Candida score by analyzinge the relationship with multidrug-resistant (MDR) pneumonia and prognosis in patients with airway Candida colonization. @*Materials and Methods@#This study was a retrospective review of patients with airway Candida colonization by bronchial washing or bronchoalveolar lavage. The Candidascore was calculated according to the four factors (severe sepsis, surgery at baseline, total parenteral nutrition, and multifocal Candida colonization). Pneumonia related mortality or hopeless discharge expecting death was defined as a poor outcome. @*Results@#A total of 148 patients were enrolled in the study. In a multivariate analysis model, Candida score was identified as an independent predictor of poor outcomes (odds ratio 2.23;95% confidential interval 1.57 – 3.17; P<0.001) in pneumonia patients with airway Candida colonization. With a Candida score of three or higher compared with low score group, it was associated with bacterial pneumonia, especially methicillin-resistant Staphylococcus aureus (MRSA) infection (0.0% vs. 15.2%, P = 0.004). In addition, patients with a high Candida score had a longer hospital stay (13 vs. 38 days, P <0.001), longer duration of intensive care (7 vs.18 days, P <0.001), and higher pneumonia-related mortality (0.0% vs. 45.5%,P <0.001) as compared to the low Candida score group. The Candida score showed a positive correlation with other pneumonia severity scales such as CURB-65 (Confusion, Urea, Respiratory rate, Blood pressure, and age ≥65 years) (r = 0.461, P <0.001), Pneumonia Severity Index (r = 0.397, P <0.001), and predisposition, insult, response, and organ dysfunction (PIRO) score (r = 0.425, P <0.001). @*Conclusion@#This study revealed that Candida is no longer a bystander of airway colonization, and that it affects the progression of bacterial pneumonia, including multidrug-resistant pathogens, particularly MRSA infection. Also Candida score can be used to predict the prognosis of patients with pneumonia.

Clinical outcomes in pediatric patients with normal renal histopathology

There have been some cases where abnormal histopathologic findings could not be found in the kidney could even with proper specimen collection through percutaneous renal biopsy (PRB) in accordance with its indication. We analyzed the incidence and clinical outcomes of children who showed normal histopathological findings in their PRBs. Methods: The medical records of 552 pediatric subjects who underwent PRB between 2005 and 2016 were reviewed. Twenty-six subjects were excluded because allograft biopsy was performed in nine subjects, and the age at biopsy was greater than 18 years in 17 subjects. Finally, 526 subjects were enrolled in this study. Results: Of the 526 pediatric patients, 32 (6.1%) showed no histopathological abnormalities in their PRBs. The male-to-female ratio of the patients was 1.9:1, and the mean ages at the first visit and at biopsy were 10.6 ± 4.1 and 11.4 ± 3.8 years, respectively. In accordance with the biopsy indications, recurrent gross hematuria showed the highest incidence rate, but combined hematuria and proteinuria had the lowest incidence rate regarding normal renal histopathology among all the subjects. At a mean follow-up of 35.5 ± 23.6 months, urinary abnormalities had improved in more than 50% of the subjects with normal renal histopathology, and none of the patients showed progression to end-stage renal disease or required rebiopsy due to symptom worsening during the follow-up period. Conclusion: The clinical outcomes of children with normal PRB histopathologic findings are generally good. Further studies to evaluate their long-term outcomes are needed.

Acute Ischemic Stroke Caused by Detachment of Cardiac Papillary Fibroelastomas

Cardiac papillary fibroelastomas are associated with a high risk of systemic embolization in spite of benign nature. We report a case of 85-year-old patient with left supraclinoid internal carotid artery occlusion who treated with aspiration thrombectomy. Despite of the absence of residual mass on echocardiography, we could analyze pathologic specimens using retrieved embolus and confirmed cardiac papillary fibroelastoma as a rare cause of stroke.

Neuronal Intranuclear Inclusion Disease with Abnormal Peripheral Nerve Conduction

A 70-year-old female presented with progressive gait disturbance. Neurologic examination revealed sensory impairment, hyporeflexia, and sensory ataxia. Nerve conduction study demonstrated mildly decreased velocity in motor nerves. Brain magnetic resonance imaging showed high signal intensities in the corticomedullary junction on diffusion weighted imaging. Neurocognitive function test implied mild cognitive impairment. Based on eosinophilic intranuclear inclusions in pathology, neuronal intranuclear inclusion disease was confirmed. Neuronal intranuclear inclusion needs to be considered when abnormal nerve conduction studies are consistent with abnormal brain imaging findings.

A Multi-Center, Double-Blind Randomized Controlled Phase III Clinical Trial to Evaluate the Antiviral Activity and Safety of DA-2802 (Tenofovir Disoproxil Orotate) and Viread (Tenofovir Disoproxil Fumarate) in Chronic Hepatitis B Patients

Background@#Tenofovir disoproxil fumarate (TDF, Viread® ) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. @*Methods@#The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. @*Results@#A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was −5.13 ± 1.40 in the DA-2802 group and −4.97 ± 1.40 log 10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. @*Conclusion@#DA-2802 is considered an effective and safe treatment for patients with CHB.

Cumulative Sum Analysis of the Learning Curve of Free Flap Reconstruction in Head and Neck Cancer Patients

Objectives@#. Owing to the functional and structural complexity of the head and neck area, the reconstruction of defects in these areas is challenging. Free flap surgery has become standard for the reconstruction of the head and neck with improvements in microvascular surgery. The aim of this study was to use the cumulative sum (CUSUM) method to evaluate the learning curve for free-flap head and neck reconstruction performed by a single surgeon. @*Methods@#. We retrospectively reviewed the medical records of 47 patients who underwent free-flap reconstruction from 2017 to 2021. The clinical demographics and surgical outcomes were analyzed. The total operation time was analyzed using the CUSUM method, which is an analytical approach for visualizing patterns in data by converting raw data into an accumulation of deviations from the average value. @*Results@#. CUSUM analysis showed two phases of the learning curve: phase 1 (cases 1–22) and phase 2 (cases 23–47). The operative time in phase 1 (579.9±128.2 minutes) was significantly longer than that in phase 2 (418.6±80.9 minutes) (P<0.001). The re-exploration rate was higher in phase 1 (31.8%) than in phase 1 (4%) (P=0.018). The flap failure rate was higher in phase 1 (9.1%) than in phase 1 (4%), but this difference was not statistically significant (P=0.593). @*Conclusion@#. The learning curve of free-flap head and neck reconstruction seems to stabilize after approximately 20 cases.

Circulating Cancer Stem Cells Expressing EpCAM/CD90 in Hepatocellular Carcinoma: A Pilot Study for Predicting Tumor Recurrence after Living Donor Liver Transplantation

Background/aims@#Circulating tumor cells (CTCs) with cancer stemness have been demonstrated to be a direct cause of tumor recurrence, and only few studies have reported the role of CTCs in liver transplantation (LT) for hepatocellular carcinoma (HCC). @*Methods@#Epithelial cell adhesion molecule+ (EpCAM+), cluster of differentiation 90+ (CD90+) and EpCAM+/CD90+ CTCs were sorted via fluorescence-activated cell sorting, and transcripts level of EpCAM, K19 and CD90 in the peripheral blood were analyzed via real-time polymerase chain reaction preoperatively and on postoperative days 1 and 7 in 25 patients who underwent living donor liver transplantation (LDLT) for HCC. EpCAM protein was assessed in HCC tissue using immunohistochemical staining. The median follow-up duration was 40 months. @*Results@#HCC after LDLT recurred in four out of 25 patients. Detection of EpCAM+ or CD90+ CTCs correlated well with their messenger RNA levels (p100 mAU/mL and postoperative day 1 EpCAM+/CD90+ CTCs were independent risk factors for HCC recurrence (hazard ratio, 14.64; 95% confidence interval, 1.08 to 198.20; p=0.043 and hazard ratio, 26.88; 95% confidence interval, 1.86 to 387.51; p=0.016, respectively). @*Conclusions@#EpCAM+/CD90+ CTCs can be used preoperatively and 1 day after LDLT as key biological markers in LT candidate selection and post-LDLT management.