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Background:The aim of this study was to investigate the relationship between changes in breast density during menopause and breast cancer risk.Methods:This study was a retrospective, longitudinal cohort study for women over 30 years of age who had undergone breast mammography serially at baseline and postmenopause during regular health checkups at Samsung Medical Center. None of the participants had been diagnosed with breast cancer at baseline. Mammographic breast density was measured using the American College of Radiology Breast Imaging Reporting and Data System.Results:During 18,615 person-years of follow-up (median follow-up 4.8 years; interquartile range 2.8–7.5 years), 45 participants were diagnosed with breast cancer. The prevalence of dense breasts was higher in those who were younger, underweight, had low parity or using contraceptives. The cumulative incidence of breast cancer increased 4 years after menopause in participants, and the consistently extremely dense group had a significantly higher cumulative incidence (CI) of breast cancer compared with other groups [CI of extremely dense vs. others (incidence rate per 100,000 person-years): 375 vs. 203, P < 0.01].Conclusion:Korean women whose breast density was extremely dense before menopause and who maintained this density after menopause were at two-fold greater risk of breast cancer.Prevention Relevance:Extremely dense breast density that is maintained persistently from premenopause to postmenopause increases risk of breast cancer two fold in Korean women. Therefore, women having risk factors should receive mammography frequently and if persistently extremely dense breast had been detected, additional modalities of BC screening could be considered.

Neuroendocrine tumors (NETs) can arise throughout the body. Most NETs in the liver are metastatic tumors; primary hepatic NET (PHNET) is extremely rare. A diagnosis of PHNET is very difficult. No single modality can diagnose PHNET by itself, and it often resembles other hypervascular masses of the liver. This paper reports the case of a 51-year old female with a large hepatic mass. Unlike most of PHNETs reported previously, it was composed of a solid mass with mainly multiple cystic lesions, which led to an erroneous diagnosis of hepatic mucinous cystadenoma or cystadenocarcinoma. PHNET with cystic lesions is extremely rare, and the features are not well studied. This case may help physicians suspect PHNET in a differential diagnosis of an atypical hepatic mass.

Aim Recent evidence has revealed an association between neurodegenerative disorders and olfactory dysfunction. However, whether olfactory training can improve cognitive impairment in patients with dementia requires further study. The present study aimed to resolve this by developing an intensive olfactory training (IOT) protocol and assessing its impact on each of the cognitive domains in patients with dementia. Methods Patients were prospectively recruited between June 2020 and September 2020. Baseline evaluations included demographic data, olfactory function test, depression scale and detailed cognitive function tests. Thirty-four patients in the experimental group underwent IOT twice a day with a 40-odor set for 15 days, while 31 individuals in the control group received conservative management. Follow-up evaluations using the depression scale and detailed cognitive function tests were performed after IOT. Results Baseline characteristics were not different between the two groups. The IOT group showed significant improvements in depression, attention, memory and language functions, but not global cognition, frontal executive, or visuospatial functions compared with the control group. Conclusion This study shows the ability of IOT to alleviate depression and improve some cognitive functions in patients with dementia. These results suggest that IOT may be an effective non-pharmacological approach for improving the symptoms of dementia. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2021; ••: ••-••.

Background Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using a lumen-apposing metal stent (LAMS) has rendered endoscopic gallbladder assessment through a stent possible, but an appropriate endoscope is required. We assessed the feasibility of peroral cholecystoscopy (POCC) using a multibending ultraslim endoscope passed through a LAMS after EUS-GBD. Methods 14 patients with a LAMS for EUS-GBD who consecutively underwent POCC were included. POCC was performed using a multibending endoscope inserted through the LAMS. The primary outcome was the technical success rate, defined as complete endoscopic examination of the gallbladder from the orifice of the cystic duct to the fundus. The types of intervention and adverse events were recorded. Results 17 POCCs were performed in 14 patients. Of the 17 POCCs, 15 (88.2 %) were technically successful. Narrow-band imaging endoscopy was performed in 12 procedures (70.6 %), and cholecystoscopy-guided target biopsies were obtained in six. Gallstone extraction was performed in two patients. After POCC, all LAMSs remained stable and no adverse events were observed. Conclusions POCC using a multibending ultraslim endoscope can be effectively and safely performed through a LAMS after EUS-GBD.

Purpose To assess the efficacy and safety of the Orchid drug-coated balloon (coated with paclitaxel) for the treatment of femoropopliteal artery disease versus percutaneous transluminal angioplasty in Chinese population. Methods This is a prospective, single center, single-blinded, randomized controlled trial that randomized (1:1) 60 patients (38 men; mean age 68.7 ± 8.8) to drug-coated balloon group ( n = 30) or percutaneous transluminal angioplasty group ( n = 30). The primary efficacy endpoint was primary patency of the target lesion and clinically driven target lesion revascularization (CD-TLR) at 12 months. The primary safety end point was freedom from perioperative death at 30 days and freedom from limb-related death and major amputation at 12 months. Results Baseline characteristics were similar between the two groups. Drug-coated balloon group resulted in higher primary patency (82.8% vs. 48.3%, p = 0.005) and lower CD-TLR rates (3.5% vs. 27.6%; p = 0.001) versus percutaneous transluminal angioplasty group at 12 months. The ABI was significantly higher in drug-coated balloon group than percutaneous transluminal angioplasty group (0.86 ± 0.13 vs. 0.72 ± 0.18, p = 0.025). There were no perioperative death at 30 days, no limb-related death and no major amputation at 12 months in either group. Conclusions The randomized controlled trial showed superior treatment effect with drug-coated balloon versus percutaneous transluminal angioplasty, with remarkably higher patency and lower CD-TLR rates. The result is consistent with other study and demonstrates the safety and efficacy of the Orchid drug-coated balloon for the treatment of femoropopliteal artery disease.

Background Radial artery cannulation can cause complications such as haematoma formation or thrombosis due to its small diameter. Recently, a novel ultrasound device equipped with an electromagnetic guidance system was introduced, showing the path and alignment of the needle during the procedure. The aim of this study was to investigate the effects of this novel system on both success and complication rates during radial artery cannulation under ultrasound guidance. Methods In this randomized controlled trial, 76 adults scheduled for neurosurgery requiring radial artery cannulation were recruited. In group E (n = 38), radial artery cannulation was performed using the electromagnetic guidance ultrasound system, whereas in group C (n = 38), the procedure was performed using conventional ultrasound guidance. The success rates of cannulation on the first attempt, cannulation times, number of attempts, and incidence of complications were compared between the two groups. Results There was a significant difference in the success rates on the first attempt between the two groups (group C = 78.9% vs. group E = 94.7%, P = 0.042). Incidences of posterior wall puncture and haematoma formation (group C = 8 vs. group E = 1; P = 0.028) were significantly lower in group E than in group C. The median cannulation time for successful attempts was comparable between groups. Conclusions Use of the novel electromagnetic guidance system resulted in a better success rate on the first attempt and a lower incidence of complications during radial artery cannulation. Trial registration This study was registered at http://cris.nih.go.kr (registration number: KCT0002476).

Objective The objective of this study was to evaluate the efficacy and safety of radiofrequency-induced thermotherapy (RFiTT) combined with transilluminated powered phlebectomy (TIPP) in the treatment of lower limb varicose veins (VVs) in comparison with high ligation and stripping (HLS) combined with TIPP. Methods The patients with lower limb VVs were randomly assigned to RFiTT combined with TIPP or HLS combined with TIPP. The primary end point was total closure rate of the great saphenous vein at 12 months. Secondary end points included Venous Clinical Severity Score and 14-item Chronic Venous Insufficiency Questionnaire score changes at 12 months and perioperative complications. Results The total closure rate of the great saphenous vein at 12 months was slightly lower in the RFiTT group (90.9% [90/99]) than in the HLS group (97.0% [98/101]) but not statistically significant (χ2 = 0.068; P = .08). Operation time, intraoperative blood loss, duration in hospital, duration in bed, and resumption of activities were statistically significantly better with RFiTT than with HLS. There were no significant differences between the groups in deep venous thrombosis, phlebitis, hematomas, pain, and infection. However, skin pigmentation and paresthesia were statistically significantly better with RFiTT than with HLS. At 12 months, both groups showed similar improvement from baseline in Venous Clinical Severity Score (1.28 ± 0.57 in the RFiTT group vs 1.33 ± 0.61 in the HLS group) and 14-item Chronic Venous Insufficiency Questionnaire score (67.32 ± 1.29 in the RFiTT group vs 67.45 ± 1.32 in the HLS group); however, neither group was superior to the other. Conclusions RFiTT combined with TIPP is an effective treatment method for lower limb VVs and had a more satisfactory clinical outcome in surgical data, skin pigmentation, and paresthesia than HLS at the 12-month follow-up.

Side effects of tattoos can occur due to unexpected body responses. Concerns about the side effects of tattoos are growing concomitantly with the increasing number of tattooed individuals. We report a rare case of basal cell carcinoma (BCC) on a tattooed eyebrow. A 48-year-old woman with no family history or occupational risk of skin cancer had her eyebrows tattooed 6 years prior, and she noticed a black mass on her right eyebrow 1 year before presentation. Staged excision was planned due to the patient’s reluctance regarding the possibility of a wide scar. After the first surgical procedure, a histopathological examination confirmed BCC. Wide excision and primary closure were performed for remnant BCC, and no recurrence was observed. The mechanism of skin neoplasms involving tattoos has not been clearly identified. Unapproved tattoo inks contain carcinogenic substances, and previous case reports indicate that skin neoplasms may differ depending on the tattoo color. Therefore, the carcinogenic effects of these unknown components of tattoo ink might cause skin neoplasms. Accurate component analysis and systematic management of tattoo ink is necessary, and medical practitioners must also pay attention to this possibility because it is easy to overlook tattoos as a causal factor contributing to cancer.

Background Ventilator-dependent patients in the intensive care unit (ICU) who are difficult to wean from invasive mechanical ventilation (IMV) have been increasing in number. However, data on the clinical outcomes of difficult-to-wean patients are lacking. We aimed to evaluate clinical outcomes in patients discharged from the ICU with tracheostomy and ventilator dependency. Methods We retrospectively investigated clinical course and survival in patients requiring home mechanical ventilation (HMV) with a tracheostomy and difficulty weaning from IMV during medical ICU admission from September 2013 through August 2016 at Severance Hospital, Yonsei University, Seoul, Korea. Results Of 84 difficult-to-wean patients who were started on HMV in the medical ICU, 72 survived, were discharged from the ICU, and were included in this analysis. HMV was initiated after a median of 23 days of IMV, and the successful weaning rate was 46% (n=33). In-hospital mortality rate was significantly lower in the successfully weaned group than the unsuccessfully weaned group (0% vs. 23.1%, respectively; P=0.010). Weaning rates were similar according to primary diagnosis, but high body mass index (BMI), low Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score at ICU admission, and absence of neuromuscular disease were associated with weaning success. After a median follow-up of 4.6 months (range, 1-27 months) for survivors, 3-month (n=64) and 6-month (n=59) survival rates were 82.5% and 72.2%, respectively. Survival rates were higher in the successfully weaned group than the unsuccessfully weaned group at 3 months (96.4% vs. 69.0%; P=0.017) and 6 months (84.0% vs. 62.1%; P=0.136) following ICU discharge. Conclusions In summary, 46% of patients who started HMV were successfully weaned from the ventilator in general wards. High BMI, low APACHE II score, and absence of neuromuscular disease were factors associated with weaning success.

Background. Many different operative options have been used to cover sacral defects. Perforator flap enables wide defect reconstruction with long pedicle and a large arc of rotation while preserving gluteus maximus muscle, but the risk of vessel injury can jeopardize flap survival. Perforator-based flap, the flap transposed without skeletonization of the perforator, requires much experience to be perfect in flap design to achieve tension-free closure. Methods. Fourteen modified parasacral perforator-based flap procedures were carried out on 14 patients. The records of patients at Chungnam National University Hospital from February 2017 to January 2020 were retrospectively reviewed. Results. All 14 flaps survived completely. One patient developed localized hematoma, and another presented with latent seroma. No donor or recipient site dehiscence or recurrence occurred during follow-up. Conclusion. We present our experience of a parasacral perforator-based flap with modified design of bilobed flaps. It could be performed easily and safely with less wound dehiscence and serve as a good practice model for young surgeons to cover small to moderately sized defects.

Background. Nonalcoholic fatty liver disease (NAFLD) may develop into liver cirrhosis and hepatocellular carcinoma (HCC). The aim of this study was to compare the clinical patterns and survival outcomes of NAFLD-related HCC patients and those of alcoholic liver disease (ALD)-related or hepatitis B virus (HBV)-related HCC patients. Methods. A total of 622 HCC patients with associated NAFLD (n = 56), ALD (n = 173), or HBV infection (n = 393) were enrolled. The clinical characteristics and survival were analyzed according to the underlying liver diseases. Results. NAFLD-related HCC patients were more commonly older women and had more metabolic risk factors but were less likely to have cirrhosis and ascites, compared to ALD-related or HBV-related HCC patients. NAFLD-related HCC more often had an infiltrative pattern (P=0.047), a larger tumor (P=0.001), more macrovascular invasion (P=0.022), and exceeded the Milan criteria (P=0.001), but was less frequently diagnosed during tumor surveillance (P=0.025). Survival analysis did not show any difference among NAFLD-related, ALD-related, and HBV-related HCC patients. Furthermore, propensity score matching analysis did not reveal a significant difference in the median survival between the different groups (NAFLD vs. ALD, 14.0 months [95% confidence interval (CI), 2.0–26.0] vs. 13.0 months [95% CI, 0–26.3]; P=0.667, NAFLD vs. HBV, 14.0 months [95% CI, 2.0–26.0] vs. 12.0 months [95% CI, 4.3–17.8]; P=0.573). Conclusions. NAFLD-related HCCs were more often detected at an advanced stage with infiltrative patterns, although they showed no significant difference in survival compared to ALD-related or HBV-related HCCs. A future prospective research should be focused on identifying NAFLD patients who require strict surveillance in order to early detect and timely treat HCC.

The CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor that regulates chemotaxis and effector functions of immune cells. It also serves as the major co-receptor for the entry of human immunodeficiency virus (HIV). Recently, CCR5 inhibitors have been developed and used for the treatment or prevention of HIV infections. Additionally, it has been identified that CCR5 controls bone homeostasis by regulating osteoclastogenesis and the communication between osteoblasts and osteoclasts. However, the effects of CCR5 inhibition on bone tissue in elderly patients are unknown. This study aimed to examine the bone phenotype of aged CCR5 knockout (KO) mice. Femoral and tibial bones were isolated from 12-month and 18-month old wild-type (WT) and CCR5 KO mice, and microcomputed tomography and histology analyses were performed. Twelve-month-old CCR5 KO mice exhibited a decreased trabecular bone mass and cortical bone thickness in both femoral and tibial bones compared with agematched WT mice. Eighteen-month-old mice also showed a decreased trabecular bone mass in femurs compared with control WT mice, but not in tibial bones. Unlike in 12-month-old mice, the cortical margin of femurs and tibias in 18-month-old mice were rough, likely because they were aggravated by the deficiency of CCR5. Overall, our data suggest that the deficiency of CCR5 with aging can cause severe bone loss. When CCR5 inhibitors or CCR5 inactivating technologies are used in elderly patients, a preventive strategy for bone loss should be considered.

To investigate clinical features and treatment outcomes of pingueculitis with morphological assessments using anterior segment optical coherence tomography (AS-OCT).In this retrospective observational study, we examined 22 eyes of 22 patients with pingueculitis. All patients were treated with the same 2-week course of prednisolone acetate 1% drops four times per day. The clinical parameters evaluated were surface dimensions determined by slitlamp biomicroscopy, cross-sectional dimensions determined by AS-OCT, and symptom scores determined by patient surveys. Pretreatment and 1-month posttreatment values were compared with Wilcoxon signed-rank tests. Patients were followed up to 1 year after treatment.Twenty-two eyes from 22 patients (4 men and 18 women) with an average age of 37.7±8.8 (range, 27-57) years and an average duration of symptoms of 22 (range, 5-60) days were included. The average follow-up period was 14.7±0.8 (range, 12-22) months. Mean pretreatment horizontal length, vertical length, conjunctival thickness, and cross-sectional area were 2.4±0.69 mm, 2.0±0.6 mm, 1.82±0.60 μm, and 5.14±2.05 mm, respectively. Mean posttreatment horizontal length, vertical length, conjunctival thickness, and area were 1.93±0.5 mm, 1.52±0.6 mm, 1.03±0.46 μm, and 2.33±0.83 mm, respectively. Mean pretreatment and posttreatment dry eye symptom scores were 3.27±0.77 and 1.13±0.38, respectively. The median pretreatment and posttreatment changes were statistically significant by Wilcoxon signed-rank tests for horizontal length (P0.001), vertical length (P0.001), conjunctival thickness (P=0.003), cross-sectional area (P=0.003), and dry eye symptom scores (P0.001).Anterior segment optical coherence tomography allows the quantification of differences in the pingueculitis measurements before and after treatment. In this retrospective study, a short course of topical steroids effectively treated the inflammation in a sustained manner. Anterior segment optical coherence tomography demonstrated significant reduction in the thickness and cross-sectional area of the pinguecula and a conversion back to a homogeneous conjunctival stroma.

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 525 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we show that CH is associated with severe Covid-19 outcomes (OR = 1.85, 95%=1.15–2.99, p = 0.01), in particular CH characterized by non-cancer driver mutations (OR = 2.01, 95% CI = 1.15–3.50, p = 0.01). We further explore the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH is significantly associated with risk of Clostridium Difficile (HR = 2.01, 95% CI: 1.22–3.30, p = 6×10−3) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15–2.13, p = 5×10−3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation., Clonal haematopoiesis (CH) has been associated with altered inflammatory profiles and increased risk of cardiovascular and malignant diseases. Here, the authors analyze patient data from two different cohorts and show that CH is associated with severe infections and severe Covid19.

Background: GLI-Kruppel family member 3 (GLI3), a zinc finger transcription factor of the sonic hedgehog pathway, is essential for organ development. Mutations in GLI3 cause several congenital conditions, including Pallister-Hall syndrome (PHS), which is characterized by polydactyly and hypothalamic hamartoma. Most patients are diagnosed soon after birth, and surgical removal of hypothalamic hamartoma in the very young is rarely performed because of associated risks.Case presentation: A 7-month-old boy with PHS features, including a suprasellar lesion, bifid epiglottis, tracheal diverticulum, laryngomalacia, left-handed polydactyly and syndactyly, and omental hernia was referred to our service. His suprasellar lesion was partially removed, and whole-exome sequencing was applied to the resected tumor, his peripheral blood, and blood from his parents. Histopathology confirmed the diagnosis of hypothalamic hamartoma, and molecular profiling revealed a likely pathogenic de novo variant, c.2331C>G (p. H777Q), in GLI3. Magnetic resonance imaging follow-up 1 year later showed some residual tumor, and the patient experienced normal development post operation.Conclusions: We presented a case of PHS that carries a novel GLI3 variant. Hypothalamic hamartoma showed a distinct genetic landscape from germline DNA. These data offer insights into the underlying etiology of hypothalamic hamartoma development in patients with PHS.

Virtual reality (VR)-based therapies are widely used in stroke rehabilitation. Although various studies have used VR techniques for bilateral upper limb training, most have been only semi-immersive and have only been performed in an artificial environment. This study developed VR content and protocols based on activities of daily living to provide immersive VR-based bilateral arm training (VRBAT) for upper limb rehabilitation in stroke patients. Twelve patients with chronic stroke were randomized to a VRBAT group or a normal bilateral arm training (NBAT) group and attended 30-min training sessions five times a week for four weeks. At the end of the training, there was a significant difference in upper limb function in both groups (p &lt, 0.05) and in the upper limb function sensory test for proprioception in the NBAT group (p &lt, 0.05). There was no significant between-group difference in upper limb muscle activity after training. The relative alpha and beta power values for electroencephalographic measurements were significantly improved in both groups. These findings indicate that both VRBAT and NBAT are effective interventions for improving upper limb function and electroencephalographic activity in patients with chronic stroke.

Research on vitamin D in patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) is limited. We aimed to compare the vitamin D parameters of patients with NTM-PD to those of a healthy control group, and to assess the possible predictive markers for a clinical response. We prospectively enrolled 53 patients with NTM-PD between January 2014 and December 2016. The clinical data and vitamin D indices, including total, free, bioavailable 25-(OH)D, and vitamin D binding protein (VDBP) genotyping, were measured at baseline and six months after enrollment. An external dataset of 226 healthy controls was compared with the NTM-PD group. The mean age of subjects was 53 years, 54.5% were male. The NTM-PD group was older, predominantly female, and had a lower body mass index (BMI) than the controls. The proportion of patients with vitamin D concentration &lt, 50 nmol/L was 52.8% in the NTM-PD group and 54.9% in the control group (p = 0.789). The bioavailable 25-(OH)D concentrations of the NTM-PD group and the controls were similar (6.9 nmol/L vs. 7.6 nmol/L, p = 0.280). In the multivariable analysis, bioavailable 25-(OH)D concentrations were associated with NTM-PD, adjusting for age, sex, BMI, and VDBP levels. Bioavailable 25-(OH)D concentrations were significantly associated with susceptibility to NTM-PD, but not with treatment outcomes. Lower bioavailable 25-(OH)D might be a risk factor for NTM-PD.

Lead (Pb) can cause a significant neurotoxicity in both adults and children, leading to the impairment to brain function. Pb exposure plays a key role in the impairment of learning and memory through synaptic neurotoxicity, resulting in the cognitive function. Researches have demonstrated that Pb exposure plays an important role in the etiology and pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease. However, the underlying mechanisms remain unclear. In the current study, a gestational Pb exposure (GLE) rat model was established to investigate the underlying mechanisms of Pb-induced cognitive impairment. We demonstrated that low-level gestational Pb exposure impaired spatial learning and memory as well as hippocampal synaptic plasticity at postnatal day 30 (PND 30) when the blood concentration of Pb had already recovered to normal levels. Pb exposure induced a decrease in hippocampal glucose metabolism by reducing glucose transporter 4 (GLUT4) levels in the cell membrane through the phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) pathway. In vivo and in vitro GLUT4 over-expression increased the membrane translocation of GLUT4 and glucose uptake, and reversed the Pb-induced impairment to synaptic plasticity and cognition. These findings indicate that Pb exposure impairs synaptic plasticity by reducing the level of GLUT4 in the cell membrane as well as glucose uptake via the PI3K-Akt signaling pathway, demonstrating a novel mechanism for Pb exposure-induced neurotoxicity., Graphical Abstract

The 2019 novel coronavirus has spread rapidly around the world. Cancer patients seem to be more susceptible to infection and disease deterioration, but the factors affecting the deterioration remain unclear. We aimed to develop an individualized model for prediction of coronavirus disease (COVID‐19) deterioration in cancer patients. The clinical data of 276 cancer patients diagnosed with COVID‐19 in 33 designated hospitals of Hubei, China from December 21, 2019 to March 18, 2020, were collected and randomly divided into a training and a validation cohort by a ratio of 2:1. Cox stepwise regression analysis was carried out to select prognostic factors. The prediction model was developed in the training cohort. The predictive accuracy of the model was quantified by C‐index and time‐dependent area under the receiver operating characteristic curve (t‐AUC). Internal validation was assessed by the validation cohort. Risk stratification based on the model was carried out. Decision curve analysis (DCA) were used to evaluate the clinical usefulness of the model. We found age, cancer type, computed tomography baseline image features (ground glass opacity and consolidation), laboratory findings (lymphocyte count, serum levels of C‐reactive protein, aspartate aminotransferase, direct bilirubin, urea, and d‐dimer) were significantly associated with symptomatic deterioration. The C‐index of the model was 0.755 in the training cohort and 0.779 in the validation cohort. The t‐AUC values were above 0.7 within 8 weeks both in the training and validation cohorts. Patients were divided into two risk groups based on the nomogram: low‐risk (total points ≤ 9.98) and high‐risk (total points > 9.98) group. The Kaplan‐Meier deterioration‐free survival of COVID‐19 curves presented significant discrimination between the two risk groups in both training and validation cohorts. The model indicated good clinical applicability by DCA curves. This study presents an individualized nomogram model to individually predict the possibility of symptomatic deterioration of COVID‐19 in patients with cancer., This is the first study to present a nomogram model to individually predict the deterioration of COVID‐19 in cancer patients. Clinical symptoms, computed tomography image features, cancer types, and comorbidities were incorporated in the model. Risk stratification was carried out targeting cancer populations for COVID‐19 deterioration. Cancer type was a critical factor affecting symptomatic deterioration. The COVID‐19 patients with lymphoma had the highest risk score for symptomatic deterioration.

ObjectiveTo investigate the effect of different aspects of inequality on childhood immunisation rates in Nepal. The study hypothesised that social inequality factors (eg, gender of a child, age of mother, caste/ethnic affiliation, mother’s socioeconomic status, place of residence and other structural barrier factors such as living in extreme poverty and distance to health facility) affect the likelihood of children being immunised.DesignUsing gender of a child, age of mother, caste/ethnic affiliation, mother’s socioeconomic status, place of residence and other structural barrier factors such as living in extreme poverty and distance to health facility as independent variables, we performed bivariate and multivariate logistic regression analyses.SettingThis study used data from the most recent nationally representative cross-sectional Nepal Demographic and Health Survey in 2016.ParticipantsThe analysis reviewed data from 1025 children aged 12–23 months old.Outcome measuresThe main outcome variable was childhood immunisation.ResultsOnly 79.2% of children were fully immunised. The complete vaccination rate of ethnic/caste subpopulations ranged from 66.4% to 85.2%. Similarly, multivariate analysis revealed that children from the previously untouchable caste (OR 0.58; CI 0.33 to 0.99) and the Terai caste (OR 0.54; CI 0.29 to 0.99) were less likely to be fully immunised than children from the high Hindu caste.ConclusionGiven Nepal’s limited resources, we suggest that programmes that target the families of children who are least likely to be fully immunised, specifically those who are not only poor but also in financial crises and ‘underprivileged’ caste families, might be an effective strategy to improve Nepal’s childhood immunisation rates.

Accumulating studies have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve cognitive dysfunction of the patients with schizophrenia (SCZ), but with inconsistent results. The present study aims to assess the efficacy of different frequencies of neuronavigated rTMS in ameliorating cognitive impairments and alleviating the psychotic symptoms. A total of 120 patients were randomly assigned to 3 groups: 20 Hz rTMS (n = 40), 10 Hz rTMS (n = 40), or sham stimulation (n = 40) for 8 weeks, and then followed up at week 32. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess the cognitive functions of the patients at baseline, at the end of week 8, and week 32 follow-up. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 2, week 4, week 6, week 8, and week 32 follow-up. Our results demonstrated that 20 Hz rTMS treatment produced an effective therapeutic benefit on immediate memory of patients with chronic SCZ at week 8, but not in the 10 Hz group. Interestingly, both 10 Hz and 20 Hz rTMS treatments produced delayed effects on cognitive functions at the 6-month follow-up. Moreover, in both 10 Hz rTMS and 20 Hz rTMS, the improvements in RBANS total score were positively correlated with the reduction of PANSS positive subscore at the 6-month follow-up. Stepwise regression analysis identified that the visuospatial/constructional index, immediate memory index, and prolactin at baseline were predictors for the improvement of cognitive impairments in the patients. Our results suggest that add-on HF rTMS could be an effective treatment for cognitive impairments in patients with chronic SCZ, with a delayed effect. Trial registration: clinicaltrials.gov identifier—NCT03774927.

Overexpression/amplification of erb-b2 receptor tyrosine kinase 2 (ERBB2) is a major prognostic factor in gastroesophageal cancers; it is currently the only biomarker established for the selection of targeted therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). Current standard procedure for determining ERBB2 status in such patients is immunohistochemistry (IHC), followed by in situ hybridization (ISH), when IHC result is equivocal. Insufficient knowledge regarding the utilities of chromosomal microarray (CMA) has hindered its use as an adjunct tool in ERBB2 analysis. Here, we performed CMA on 7 formalin-fixed paraffin-embedded (FFPE) GEA specimens previously tested by ERBB2 fluorescence in situ hybridization (FISH) and evaluated the concordance and performance of CMA. CMA identified 4 (57.1%) samples with amplification of ERBB2, compared to 3 (42.9%) by FISH. CMA also detected several additional DNA copy number variants in these samples, which may have prognostic and therapeutic indications. Further case studies and clinical trials may provide evidence for the utility of CMA-based genomic studies in the management of patients with suspected ERBB2-positive gastroesophageal adenocarcinoma.

Background/Aims: Sofosbuvir plus ribavirin is a standard treatment for patients infected with chronic hepatitis C virus (HCV) genotype 2 in Korea. The purpose of this study was to examine the efficacy and safety of this treatment in Korean patients with chronic HCV genotype 2 infection. Methods: We retrospectively analyzed clinical data of patients treated with sofosbuvir plus ribavirin for chronic HCV genotype 2 from May 2016 to December 2017 at eight hospitals located in the Daejeon-Chungcheong area. Results: A total of 172 patients were treated with sofosbuvir plus ribavirin. Of them, 163 patients completed the treatment, and 162 patients were tested for sustained virologic response 12 weeks after treatment discontinuation (SVR12). Mean age was 59.6±12.3 years (27-96), and 105 (64.4%) patients were female. Of the total patients, 49 (30.1%) were diagnosed with cirrhosis, and 31 of them were treated for 16 weeks. Sofosbuvir plus ribavirin was the first-line treatment for 144 (88.3%) patients. Eleven (6.7%) patients were intolerant to previous interferon-based treatment. Eight (5.0%) patients relapsed after interferon-based treatment. HCV RNA non-detection rate at 4, 8, and 12 weeks was 97.5%, 99.1%, and 99.3%, respectively, and SVR12 was 98.8% (161/163). During treatment, 18 (11.0%) patients had to reduce their administrated dose of ribavirin because of anemia. One patient stopped the treatment because of severe anemia. Other adverse events, including dizziness, indigestion, and headache, were found in 26 (16.0%) patients. Conclusions: A 12-16 week treatment with sofosbuvir plus ribavirin is remarkably effective and well tolerated in Korean patients with chronic HCV genotype 2 infection. (Clin Mol Hepatol 2018;24:311-318)

Background Physical function may influence perioperative outcomes of lung transplantation. We investigated the feasibility of a pulmonary rehabilitation program initiated in the immediate postoperative period at an intensive care unit (ICU) for patients who underwent lung transplantation. Methods We retrospectively evaluated 22 patients who received pulmonary rehabilitation initiated in the ICU within 2 weeks after lung transplantation at our institution from March 2015 to February 2016. Levels of physical function were graded at the start of pulmonary rehabilitation and then weekly throughout rehabilitation according to criteria from our institutional pulmonary rehabilitation program: grade 1, bedside (G1); grade 2, dangling (G2); grade 3, standing (G3); and grade IV, gait (G4). Results The median age of patients was 53 years (range, 25 to 73 years). Fourteen patients (64%) were males. The initial level of physical function was G1 in nine patients, G2 in seven patients, G3 in four patients, and G4 in two patients. Patients started pulmonary rehabilitation at a median of 7.5 days (range, 1 to 29 days) after lung transplantation. We did not observe any rehabilitation-related complications during follow-up. The final level of physical function was G1 in six patients, G3 in two patients, and G4 in 14 patients. Fourteen of the 22 patients were able to walk with or without assistance, and 13 of them maintained G4 until discharge; the eight remaining patients never achieved G4. Conclusions Our results suggest the feasibility of early pulmonary rehabilitation initiated in the ICU within a few days after lung transplantation.

Youngmok Park, Ji Ye Jung, Young Sam Kim, Kyung Soo Chung, Joo Han Song, Song Yee Kim, Eun Young Kim, Young Ae Kang, Moo Suk Park, Joon Chang, Ah Young Leem Division of Pulmonology, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seodaemun-gu, Seoul, South Korea Background: Lung function and depression are closely related to many chronic lung diseases. However, few studies have evaluated this association in the general population. In this study, we evaluated the relationship between lung function and depression in the general population in Korea. Participants and methods: Data from the Ansung–Ansan cohort, a community-based cohort in Korea, were used to analyze the relationships between depression and lung function parameters. A total of 3,321 men and women aged 40–69years were enrolled. Spirometry data included the forced expiratory volume in 1second (FEV1), forced vital capacity (FVC), and the FEV1/FVC ratio. Depression was defined as a score of ≥16 by the Beck Depression Inventory (BDI). A propensity score analysis was conducted with the aim of reducing the bias of the retrospective study. Results: The overall prevalence of depression in the study population was 13.1% (434/3,321 participants). Depression was significantly more prevalent in women than in men (P

Background To assess the efficacy and safety of Orchid drug-coated balloon (DCB) for treatment of femoropopliteal (FP) artery in-stent restenosis (ISR) in Chinese patients. Methods The study is a prospective, single center, single-blinded, randomized controlled trial (RCT) that randomized (1:1) 74 patients to DCB group (N.=38) and PTA group (N.=36). The primary efficacy endpoint was primary patency of the target lesion at 12 months. Second efficacy endpoint included clinically-driven target-lesion revascularization (CD-TLR) and ABI change at 12 months. The primary safety endpoint included peri-operative death at 30 days, all-cause death, major amputation, and other major adverse events (MAEs) at 12 months. The primary functional endpoint included Walking Impairment Questionnaire (WIQ), quality-of-life measures (EQ-5D) and 6-minute walking test (6MWT). Results The DCB group had higher primary patency (87.9% vs. 51.6%; P=0.001) and lower rates of CD-TLR (6.1% vs. 35.5%; P=0.003) than the PTA group at 12 months. There were no peri-operative deaths, and no major amputations at 12 months in two groups. There were 1(2.6%) in the DCB group and 2 (5.6%) in the PTA group of all-cause deaths (P=0.524). Conclusions Results from the study showed superior treatment effect with Orchid DCB versus PTA for the treatment of FP ISR, and without an apparent difference in safety.

The prognostic value of central lymph node (CLN) status in papillary thyroid cancer (PTC) remains controversial. This study aimed to provide the first evidence on this issue for the aggressive tall-cell variant (TCV) subtype.The study identified TCV patients from the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method, log-rank test, and multivariate Cox regression models were used for analysis.Of the 744 patients included, 404 were recorded as N0, which were pathologically or only clinically confirmed. Overall survival (OS) and cancer-specific survival (CSS) did not differ significantly between the N0 and pN1a patients (p 0.05). To investigate the reason, the N0 patients were subdivided according to the number of examined lymph nodes (ELN). The patients with a N0 diagnosis confirmed by two or more ELNs (N0-e2+) showed significantly better outcomes than the pN1a patients and their N0 counterparts without ELN (N0-e0) (p 0.05), whereas the N0-e0 and pN1a groups demonstrated comparable outcomes in both the log-rank and multivariate analyses (p 0.05). Moreover, the subgroup analyses showed that even among the patients with early T-staging (T1-T2) or receipt of radioactive iodine (RAI) therapy, the N0-e0 patients still demonstrated compromised OS compared with the N0-e2+ group (p 0.05).The cN0 patients without ELN (N0-e0) had outcomes similar to those of the pN1a patients, but showed a poorer OS than the N0-e2+ group regardless of T-staging and RAI administration, suggesting that occult CLN metastases might act as a negative prognosticator in cN0 TCV. Therefore, prophylactic central neck dissection might be considered for biopsy-proven cN0 TCV patients. Prospective studies are expected to further validate our conclusions.

Background: Approximately 50% of non-small cell lung cancer (NSCLC) patients with acquired resistance to EGFR-TKI harbor the EGFR mutation T790M. The recent development and wide use of third-generation EGFR-TKIs targeting T790M-mutant NSCLCs have increased the importance of rebiopsy after EGFR-TKI failure. We aimed to investigate the advantages of flexible bronchoscopy as a rebiopsy method and the prevalence of and factors affecting the T790M mutation after EGFR-TKI failure. Methods: We investigated 139 patients who had undergone bronchoscopic rebiopsy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) between Sep 2014 and Jul 2016. Results: Among the 139 patients, bronchoscopic rebiopsy yielded successful pathological diagnoses in 102 (73.4%). Among them, 41 patients with EGFR-mutant lung adenocarcinoma and EGFR-TKI progression were selected for an investigation of T790M mutation prevalence at rebiopsy. The initial EGFR mutations were exon 19 del (56.1%), L858R or L861Q (34.1%), and others (9.8%). The most common rebiopsy method was transbronchial lung biopsy (41.5%), followed by EBUS-TBNA (26.8%) and endobronchial biopsy (19.5%). The median interval to T790M emergence was the longest among cases with exon 19 deletion (14.1 months), followed by exon 21 L858R or L861Q (11.3 months) and other rare EGFR mutations (2.9 months). The T790M mutation was identified in 18 (43.9%) patients, and exon 19 del was the most significant factor affecting T790M mutation development (hazard ratio: 6.875, P = 0.014). Conclusions: Bronchoscopy was more useful than other rebiopsy approaches. The T790M emergence rate was highest in cases with exon 19 deletion, likely as a consequence of long-term EGFR-TKI exposure.

Soft tissue loss in the lower leg presents a challenge for reconstructive surgeons. When a defect is large, free flap transfer provides a well-established method, but local flaps are more convenient for small to moderately sized soft tissue defects. When a defect is very small, even local flaps are too invasive, leave additional scar, and cause bulky flaps. We present our case aiming to underline the usefulness of percutaneous aponeurotomy and lipofilling in a small lower leg defect with several advantages.

Background: Lung transplantation is the last treatment option for end-stage lung disease, and the number of lung transplantations has been steadily increasing. Hyperbilirubinemia is a rare complication after lung transplantation. The aim of this study was to review rare causes of hyperbilirubinemia after lung transplantation at our center. Methods: In this single-center study, we retrospectively reviewed the records of 116 consecutive lung transplantation patients who underwent lung transplantation at Severance Hospital and Gangnam Severance Hospital of Yonsei University College of Medicine in South Korea between December 22, 2010 and January 1, 2016. Hyperbilirubinemia was defined as a total bilirubin level exceeding 5 mg/dL for at least 3 days after lung transplantation. Results: Hyperbilirubinemia occurred in 33 patients (28.4%) who received lung transplants at our institution. Twenty-four cases involved common causes such as drug toxicity, biliary tract stone, sepsis, and bleeding. However, rare causes of hyperbilirubinemia including hemophagocytic lymphohistiocytosis (HLH), thrombotic microangiopathy (TMA), and ischemic cholangiopathy were observed in 9 (7.8%) patients during the study period. All patients with hyperbilirubinemia due to a rare cause died despite aggressive treatment. Conclusion: Causes of hyperbilirubinemia after lung transplantation are varied, and the prognosis of patients with hyperbilirubinemia arising from rare causes was poor. Therefore, early evaluation and management of hyperbilirubinemia after lung transplantation is important to improve patient outcomes.

The aim of this single-center study is to review the transplant outcomes of patients receiving lung transplantation (LTx) using intraoperative extracorporeal membrane oxygenation (ECMO) according to the perioperative use of ECMO.We retrospectively reviewed the transplant outcomes of 107 consecutive patients who underwent LTx using intraoperative ECMO between March 2013 and August 2016 at Severance Hospital of Yonsei University (Seoul, Korea).Patients were divided into the following three groups according to the use of perioperative ECMO: only intraoperative ECMO (n=47) or extended post-operative ECMO but no bridging and no postoperative ECMO re-implantation (secondary ECMO; n=28) as Group A (n=75); bridging ECMO without secondary ECMO (n=14) as Group B; and secondary ECMO with (n=7) or without (n=11) bridging as Group C. Baseline demographics were comparable among the three groups. The mean duration of preoperative ECMO bridging was 16.4±15.6 (n=21). After a median of 17.7 months (range, 3.1-40.9 months) for survivors, the one year overall survival (OS) rates after LTx for the three groups were 76.3%±5.2% for Group A, 59.9%±14.3% for Group B, and 14.0%±9.0% for Group C (P0.0001). The secondary ECMO (Group C) was established a mean of 7.9±5.3 days after LTx. The main cause of secondary ECMO was acute respiratory failure from pneumonia, and the main cause of death was infection-related events.Our data suggests that the use of perioperative ECMO, including its extended postoperative use during LTx, is feasible and has favorable outcomes. However, as shown by the poor survival outcome after secondary ECMO, the development of solid strategy to reduce the need for secondary ECMO implantation after LTx seems important.

Background: Most studies about the risk factors of 1-year mortality after lung transplantation were performed on non-Asians. This study aimed to evaluate the perioperative factors related to the 1-year mortality after lung transplantation in Korea. Methods: Sixty-eight consecutive patients who underwent lung transplantation without preoperative extracorporeal membrane oxygenation treatment at 1 tertiary hospital in South Korea between October 24, 2012, and October 16, 2015, were analyzed retrospectively. Results: Forty-four patients (64.7%) lived for >1 year after lung transplantation. The median age of all patients was 55 years (range, 16–75 years), and men accounted for 57.4%. The major cause of lung transplantation was idiopathic pulmonary fibrosis (48.5%); the other causes were interstitial lung disease related to connective tissue disease (17.6%) and bronchiolitis obliterans after stem cell transplantation (14.7%). In univariate analysis, higher median age (52 vs . 61.5 years, P vs . 79.2%, P=0.007), lower preoperative albumin level ( vs . 45.8%, P=0.049), need for renal replacement therapy (RRT) after surgery (4.5% vs . 37.5%, P=0.001), and postoperative delta neutrophil index (DNI) >5.5 higher than the preoperative DNI (22.7% vs . 70.8%, P Conclusions: Recipients with advanced age should be carefully selected, and patients who need RRT or with increased DNI after transplantation should be managed accordingly.

BACKGROUND Mild to moderate blepharoptosis, or ptosis, is relatively common among Asians, and it is not uncommon to offer ptosis correction at the time of double-eyelid surgery in this patient population. The traditional open approaches to ptosis correction are subject to scarring and prolonged recovery time, whereas the newer nonincisional approaches are marred by issues of incomplete correction or recurrence. This study describes a new nonincisional technique that overcomes the limitations of current methods by using conjoint fascial sheath (CFS) for suspension. METHODS From January 2014 to April 2015, a retrospective review was conducted on 21 patients (41 eyelids) who underwent simultaneous nonincisional ptosis correction and double-eyelid surgery. All patients had either mild or moderate ptosis without excess skin hooding and excellent or good levator palpebrae function. RESULTS Mild ptosis correction (1-loop CFS suspension) was performed in 25 eyelids, and moderate ptosis correction (2-loop CFS suspension) was performed in 16 eyelids. At 6 months of follow-up, 23 eyelids (56.1 %) improved to "normal" with overall improvement seen in 33 eyelids (80.0%). The mean marginal reflex distance 1 increased from 3.16 ± 0.61 mm preoperatively to 4.11 ± 0.61 mm postoperatively, which was statistically significant (P < 0.001). CONCLUSIONS Mild to moderate ptosis correction with nonincisional CFS suspension technique is a safe and effective method that combines the benefits of nonincisional procedure with longevity and precision seen in the traditional open approaches. The procedure is easy to perform with minimal recovery time and high patient satisfaction and can be combined with nonincisional double-eyelid surgery.

We aimed to investigate the influence of high frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex on excitability of the masseter inhibitory reflex (MIR) in healthy subjects. Our goal in conducting this study was to obtain a better understanding of the subcortical and cortical networks related to the excitability of the central masticatory pathway.Twenty healthy volunteers participated in this study. MIRs were evaluated both before and after high frequency rTMS to elicit motor evoked potentials (MEPs) using single- and double-shock techniques over the motor cortex. During measurements, the latency and duration of silent periods (SPs) with single magnetic stimulation, and the recovery of SP2 with the double-shock technique, were recorded in basal conditions and immediately after high frequency rTMS. The "real" rTMS condition consisted of 20 stimulus trains delivered at 10Hz with a 5-s stimulation duration and an intensity of 70% of the active motor threshold (AMT) over the right optimal motor spot for the masseter muscle.were also compared to those obtained after "sham" rTMS 1 week later RESULTS: Using the double-shock technique, SP2 recovery time was significantly shorter after high frequency rTMS compared to the basal condition (from 100 to 400ms; p0.001), while at ISIs of 500 and 600ms, no significant effect was observed (p=0.084, p=0.948). There was also no significant change in the SP latency or duration between groups (p0.05).High frequency, sub-threshold rTMS of the motor cortex had a facilitative after-effect on the excitability of the MIR. This effect was likely mediated through increased cortical drive to brainstem reflex pathways, which would ultimately accelerate MIR recovery.

Although affective disorders have been known to have sex differences in the associated clinical characteristics and quality of life (QOL), sex differences among patients with panic disorder (PD) have remained relatively unexplored in Korea. We examined the sex differences in different types of stressful life events (SLEs), coping styles, symptom severity, and health-related QOL (HRQOL) in patients with PD. Data from 291 female and 254 male participants diagnosed with PD were analyzed using a structured clinical interview following the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. Females with PD reported more SLEs including separation issues, physical illness or disability, and pregnancy-related problems than males. They also reported lower levels of confrontation and help-seeking coping strategies and higher levels of agoraphobia in symptom severity than males. The HRQOL of females with PD was significantly lower than male in physical functioning of HRQOL. This study suggests that the patient's sex is relevant to the assessment and treatment of PD.

Purpose Posterior fossa epidural hematomas (PFEDH) are uncommon in children but usually require timely surgical intervention due to the risk of life-threatening brainstem compression. We attempt to make the surgical procedure less invasive by treating selected pediatric patients with trephination mini-craniectomy. Methods We retrospectively reviewed the clinical courses, radiological findings, surgical procedures, and prognoses of the pediatric patients who were treated in our departments for traumatic PFEDH from January 2010 to January 2015. Results During this period, a total of 17 patients were surgically treated for PFEDH and 7 were managed with trephination mini-craniectomy for hematoma evacuation. The outcomes were good in all 7 patients as evaluated with Glasgow Outcome Score. There was no mortality in this series. The on average 30-month clinical follow-up showed that patients experienced satisfactory recoveries without complications. Conclusion Our results suggest that trephination mini-craniectomy is a safe surgical technique for selected PFEDH patients with moderate hematoma volume and stabilized neurological functions. However, standard craniectomy is recommend when there are rapid deteriorations in patients' neurological functions or the hematomas are large and exerted severe mass effects.

Background/aims The invasiveness of a liver biopsy and its inconsistent results have prompted efforts to develop noninvasive tools to evaluate the severity of chronic hepatitis. This study was intended to assess the performance of serum biomarkers for predicting liver fibrosis in patients with chronic viral hepatitis. Methods A total of 302 patients with chronic hepatitis B or C, who had undergone liver biopsy, were retrospectively enrolled. We investigated the diagnostic accuracy of several clinical factors for predicting advanced fibrosis (F≥3). Results The study population included 227 patients with chronic hepatitis B, 73 patients with chronic hepatitis C, and 2 patients with co-infection (hepatitis B and C). Histological cirrhosis was identified in 16.2% of the study population. The grade of porto-periportal activity was more correlated with the stage of chronic hepatitis compared with that of lobular activity (r=0.640 vs. r=0.171). Fibrosis stage was correlated with platelet count (r=-0.520), aspartate aminotransferase to platelet ratio index (APRI) (r=0.390), prothrombin time (r=0.376), and albumin (r=-0.357). For the diagnosis of advanced fibrosis, platelet count and APRI were the most predictive variables (AUROC=0.752, and 0.713, respectively). Conclusions In a hepatitis B endemic region, platelet count and APRI could be considered as reliable non-invasive markers for predicting fibrosis of chronic viral hepatitis. However, it is necessary to validate the diagnostic accuracy of these markers in another population.

Background/Aims: The combination of daclatasvir (DCV) and asunaprevir (ASV) has demonstrated a high sustained virologic response at 12 weeks (SVR12) and a low rate of adverse events in previous clinical studies. The purpose of this study was to clarify the results of treatment and side effects in Korean patients with chronic hepatitis C virus (HCV) genotype Ib infection. Methods: We retrospectively analyzed clinical data from chronic HCV genotype Ib patients treated with DCV+ASV from August 2015 to September 2016 at five hospitals in the Daejeon-Chungcheong area. Results: A total of 152 patients were examined for resistance associated variants (RAVs). Among them, 15 (9.9%) were positive for Y93 and one (0.7%) was positive for L31. Of 126 patients treated with DCV+ASV, 83 patients completed treatment and 76 patients were included in safety and efficacy analysis. Five (6.6%) were positive for Y93 and 12 (15.8%) exhibited cirrhotic change. DCV+ASV was the first-line treatment for 58 (76.3%) patients. Eleven (14.5%) patients relapsed after previous treatment that included interferon and seven (9.2%) of these patients were found to be intolerant of interferon. Adverse events occurred in 10 (13.2%) patients and two patients stopped the medication because of severe itching and skin rash. SVR12 was 89.5% (68/76) in all patients and 91.5% (65/71) in RAV-negative patients. Conclusions: DCV+ASV showed good efficacy in patients with HCV Ib infection in Korea. Close monitoring is needed for severe adverse events and treatment failure, which were uncommon. (Clin Mol Hepatol 2017;23:51-56)

Background: Despite many ongoing, prospective studies on the topic, sepsis still remains one of the main causes of death in hospital. The hormone insulin-like growth factor 1 (IGF-1) has a similar molecular structure to that of insulin. IGF-1 exerts anabolic effects and plays important roles in both normal physiology and pathologic processes. Previous studies have observed low serum IGF-1 level in patients with critical illnesses. Here, we evaluated changes in IGF-1 level based on survival of septic patients. Methods: We evaluated 140 patients with sepsis and septic shock (21 with sepsis and 119 with septic shock) admitted to the intensive care unit of a university-affiliated hospital in Korea. Serum IGF-1 level was measured on days 0, 1, 3, and 7. Patients with liver disease were excluded from this study. All data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA). Results: Patients with septic shock had significantly lower serum IGF-1 level on days 1 and 3 than patients without septic shock (p = 0.002 and p = 0.007, respectively). Generally, there was a negative relationship between IGF-1 and serum cortisol levels; however, this relationship was only significant on day 3 (p = 0.029). Furthermore, renin showed significantly negative correlation with IGF-1 on day 3 (p = 0.038). IGF-1 level did not show significant difference between survivors and non-survivors. Conclusions: Our results showed that IGF-1 was associated with septic shock, and that the IGF-1 axis is severely disrupted in septic patients. Additionally, serum cortisol and renin levels were associated with IGF-1 level.

CD4+ T cell activation and adequate differentiation into effector T helper (Th) cells are crucial for mediating adaptive immune responses to cope with foreign pathogens. Despite the significant role of Th cells, excessive increases in their numbers result in inflammatory and autoimmune diseases. In this study, we investigated the effects of costunolide, a plant-derived natural compound with an anti-inflammatory activity, in regulating Th cells and the underlying mechanisms. Costunolide significantly decreased cell populations of differentiated Th1, Th2, and Th17 subsets under Th subset-polarizing conditions, while exerting statistically negligible effects on Treg cell differentiation. Furthermore, costunolide inhibited the expression level of Th subset-polarizing master genes such as T-bet, GATA3, and RORγt, indicating that costunolide inhibits the differentiation of CD4+ T cells into Th subsets. Additionally, costunolide suppressed the proliferative activity of CD4+ T cells and the expression of CD69 activation marker on CD4+ T cells. When the molecular targets of costunolide were investigated, phosphorylation of ERK and p38 was found to be decreased under Th subset-polarizing conditions, whereas activity of JNK remained unchanged. U0126, an ERK inhibitor, and SB203580, a p38 inhibitor, decreased the expression of CD69 upon TCR stimulation and inhibited CD4+ T cell differentiation, indicating that both ERK and p38 are suggested to be critical molecular targets of costunolide. Taken together, these results suggest that costunolide inhibits the differentiation of CD4+ T cells by suppressing ERK and p38 activities and can be an effective therapeutic agent for T cell-mediated immune diseases.

Background Xylocarpus granatum Koenig, widely used in folk medicine in southeast countries, has been reported to exert neuropharmacological activities as well as mood regulation. The neuroprotective activities of limonoids, riches in X. granatum, are poorly understood. Hypothesis/Purpose To investigate the potential antidepressant-like effects and the underlying mechanisms of cipadesin A, one limonoid component, extracted from X. granatum, in acute stress-induced depression mouse models. Study design Antidepressant-like effects of cipadesin A were investigated through behavioral tests, and potential mechanism was assessed by neuroendocrine system. Methods Antidepressant-like effects of cipadesin A (5, 15, 50 mg/kg/day for 7days, intragastrically) were estimated through forced-swimming test (FST), tail suspension test (TST) and open field test (OFT). Effects of cipadesin A on hypothalamus-pituitary- adrenal (HPA) axis were evaluated by analysis of serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) using enzyme-linked immunosorbent assay (ELISA). Results Cipadesin A administration significantly reduced the floating time in the FST and immobility time in the TST (15–50 mg/kg). Cipadesin A dose-dependently increased the time in the central zone in the OFT (5–50 mg/kg), without altering the locomotor activity. Moreover, repeated cipadesin A treatment significantly inhibited the increase levels of serum CORT (5–50 mg/kg), ACTH (15–50 mg/kg) following the forced swimming, but not in the absence of stress. Conclusions Cipadesin A has antidepressant-like activities in acute stressed mice model of depression, which likely occurs by inhibiting the HPA axis activity response to stress. These data support further exploration for developing cipadesin A as a potential agent to treat depression and anxiety disorders.

The peroxisome proliferator-activated receptor (PPAR)-α agonist fenofibrate is used as a lipid-lowering agent to reduce cholesterol and triglyceride in blood. In this study, we investigated whether fenofibrate affects osteoblast differentiation of osteogenic precursor cells. Quantitative real-time PCR and alkaline phosphatase (ALP) staining assays revealed that fenofibrate can enhance the osteoblast differentiation of C3H10T1/2 and MC3T3-E1 cells. In contrast with fenofibrate, the PPARγ agonist rosiglitazone decreased or did not affect the expression of osteogenic genes in these cells. Fenofibrate dose- and time-dependently increased PPARα expression, and concomitantly increased the expression of bone morphogenetic protein 2 (BMP2). Knockdown of PPARα abolished fenofibrate-induced BMP2 expression, activity of the BMP2 promoter gene, and calcium deposition. The chromatin immunoprecipitation assay demonstrated that fenofibrate increased BMP2 expression by inducing direct binding of PPARα to the BMP2 promoter region. Taken together, we suggest that fenofibrate has a stimulatory effect on osteoblast differentiation via the elevation of PPARα levels and the PPARα-mediated BMP2 expression. Our findings provide fenofibrate as a useful agent for controlling hypercholesterolemic patients with osteoporosis.