Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040.

BACKGROUND: Patients with advanced hepatocellular carcinoma (aHCC) have a poor prognosis and high mortality. Nivolumab monotherapy demonstrated clinical benefit with an acceptable safety profile in patients with aHCC in the CheckMate 040 study. Five-year follow-up of the sorafenib-naive and sorafenib-experienced groups of CheckMate 040 is presented here. PATIENTS AND METHODS: Patients received nivolumab monotherapy at dose levels of 0.1-10.0 mg/kg (dose-escalation phase) or 3 mg/kg (dose-expansion phase) every 2 weeks until disease progression or unacceptable toxicity. Primary endpoints were safety and tolerability (dose escalation), and objective response rate (ORR) by blinded independent central review (BICR) and by investigator as per RECIST version 1.1 (dose expansion). RESULTS: Eighty sorafenib-naive and 154 sorafenib-experienced patients were treated. Minimum follow-up in both groups was 60 months. ORR as per BICR was 20% [95% confidence interval (CI) 12% to 30%] and 14% (95% CI 9% to 21%) in the sorafenib-naive and sorafenib-experienced groups, respectively. Responses occurred regardless of HCC etiology or baseline tumor cell programmed death-ligand 1 (PD-L1) expression levels. Median overall survival (OS) was 26.6 months (95% CI 16.6-30.6 months) and 15.1 months (95% CI 13.0-18.2 months) in sorafenib-naive and sorafenib-experienced patients, respectively. The 3-year OS rates were 28% in the sorafenib-naive and 20% in the sorafenib-experienced groups; 5-year OS rates were 14% and 12%, respectively. No new safety signals were identified; grade 3/4 treatment-related adverse events were observed in 33% and 21% of patients in the sorafenib-naive and sorafenib-experienced groups, respectively. Biomarker analyses showed that baseline PD-L1 expression ≥1% was associated with higher ORR and longer OS compared with PD-L1 <1%. In the sorafenib-naive group, patients with OS ≥3 years exhibited higher baseline CD8 T-cell density compared with those with OS <1 year. CONCLUSION: With 5 years of follow-up, nivolumab monotherapy continued to provide durable clinical benefit with manageable safety in sorafenib-naive and sorafenib-experienced patients with aHCC.

Shear-wave velocity for colorectal cancer liver metastases as a potential prognostic factor after chemotherapy: a preliminary study.

AIM: To evaluate whether shear-wave velocity (SWV) can be used for predicting the prognoses of patients with colorectal cancer liver metastases (CRLMs) after chemotherapy. MATERIALS AND METHODS: Our institutional review board approved this prospective study, and written informed consent was obtained. SWV of CRLMs were obtained using point shear-wave elastography using acoustic radiation force impulse from 25 patients prior to and 2, 7, and 14 days after chemotherapy. Progression-free survival (PFS) after chemotherapy was estimated using the Kaplan-Meier method. The Cox proportional hazard regression model was used to determine significant predictive factors for PFS. For measurement reproducibility, an additional 37 patients with CRLMs were enrolled and assessed using intraclass correlation coefficients (ICCs). RESULTS: After chemotherapy, 10 and 15 patients were classified into responder and non-responder groups, respectively. The estimated 1- and 3-year PFS values in the whole cohort were 36% and 8%, respectively. A decrease in the SWV value on day 2 relative to the initial value was a significant predictive factor for better PFS outcome (hazard ratio = 0.20, 95% confidence interval = 0.07-0.57, p=0.003). The estimated 1 and 3-year PFS rates were 66.7% and 22.2%, respectively, in nine patients with decreased SWV values on day 2 and significantly higher than 18.8% and 0% of 16 patients with increased SWV values on day 2. The ICC value of SWV of CRLMs in the additional 37 patients was 0.823 (95% CI = 0.685-0.905), indicating good agreement. CONCLUSION: SWV values of CRLMs could provide prognostic information in patients with CRLMs treated with chemotherapy, as decreased SWV values on day 2 after chemotherapy was a significant predictive factor for better PFS.

Differentiation of dural arteriovenous fistula from reflux venous flow on 3D TOF-MR angiography: identifying asymmetric enlargement of external carotid artery branches.

AIM: To differentiate dural arteriovenous fistula (DAVF) from reflux venous flow (RVF) by assessment of asymmetric enlargement of external carotid artery (ECA) branches on three-dimensional (3D) time-of-flight magnetic resonance angiography (TOF-MRA). MATERIALS AND METHODS: Nineteen patients with DAVF and 27 patients with RVF were included from September 2007 to April 2019. The locations of DAVF were the cavernous (n=9) and sigmoid-transverse (n=6) sinuses, and the jugular (n=3) and sphenoparietal (n=1) veins. Two radiologists visually assessed asymmetric enlargement of the ascending pharyngeal artery (ASP), middle meningeal artery (MMA), accessory meningeal artery (AMA), artery of the foramen rotundum, and occipital artery. MMA size was also measured quantitatively. RESULTS: More frequent asymmetric enlargement of the ASP and MMA were seen in DAVF than in RVF (17 of 19 versus 3 of 27 for ASP; 16 of 19 versus 1 of 27 for MMA, p<0.01). The AMA, artery of the foramen rotundum, and occipital arteries were not visualised in RVF patients. The ipsilateral MMA size was significantly larger in DAVF than in RVF (2.14 versus 0.64 mm2, p< 0.01). The diagnostic performance of ipsilateral MMA size for DAVF was good, with an area under the receiver operating characteristic curve of 0.89, with a sensitivity of 84.2% and a specificity of 81.5% at a cut-off of 1.08 mm2. CONCLUSIONS: DAVF showed significantly larger ECA branches than RVF on 3D TOF-MRA. Therefore, thorough evaluation of ECA branches could help to differentiate DAVF from RVF.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with early breast cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS.

In view of the planned new edition of the most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of primary breast cancer published in 2015, it was decided at the ESMO Asia Meeting in November 2018, by both the ESMO and the Korean Society of Medical Oncology (KSMO), to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the latest ESMO 2019 guidelines to take into account the ethnic and geographical differences associated with the treatment of early breast cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with early breast cancer representing the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO) Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices, and the drug availability and reimbursement situations, in the individual participating Asian countries.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with locally-advanced unresectable non-small-cell lung cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of early and locally-advanced non-small-cell lung cancer (NSCLC) was published in 2017, and covered the diagnosis, staging, management and treatment of both early stage I and II disease and locally-advanced stage III disease. At the ESMO Asia Meeting in November 2018, it was decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the ESMO 2017 guidelines to take into account potential differences related to ethnicity, cancer biology and standard practices associated with the treatment of locally-advanced, unresectable NSCLC in Asian patients. These guidelines represent the consensus opinions reached by those experts in the treatment of patients with lung cancer who represented the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and it was independent of both local current treatment practices and the treatment availability and reimbursement situations in the individual participating Asian countries.

Shift in Sympathovagal Balance Toward Parasympathetic Predominance Is Associated With Attenuation of Portal Hyperperfusion in Cirrhotic Recipients Undergoing Living Donor Liver Transplant.

BACKGROUND: The autonomic innervation to a liver graft remains lost up to 1 year after liver transplant. Therefore, we investigated the effects of recipients' autonomic nervous activity on the extent of portal hyperperfusion of a partial liver graft in the absence of the autonomic innervation. METHODS: A total of 31 cirrhotic recipients undergoing right lobe living donor liver transplant were analyzed. Following a 10-minute absence of surgical stimulation after hepatic artery and bile duct reconstruction, the electrocardiogram and blood pressure waveforms were recorded for 5 minutes. Low-frequency (LF) and high-frequency (HF) powers and their ratio (LF/HF) were calculated using fast Fourier transform from the electrocardiogram waveform. A decrease in LF/HF represents a shift in sympathovagal balance toward parasympathetic predominance. Then, portal venous (PVF) and hepatic arterial (HAF) blood flows were measured in mL/min per 100 g of liver weight using spectral Doppler ultrasonography. A decrease in their ratio (PVF/HAF) represents attenuation of portal hyperperfusion. RESULTS: The medians of the PVF and HAF were 349 and 27 mL/min/100 g liver weight with interquartile ranges of 272 to 617 mL/min/100 g liver weight and 22 to 41 mL/min/100 g liver weight, respectively, yielding a median of the PVF/HAF of 13.7 (interquartile range, 8.5-21.3). The median of LF/HF was 0.67 (interquartile range, 0.16-1.45). With a reduction in LF/HF, PVF/HAF decreased according to an S-curve regression model between them (PVF/HAF=e2.743+-0.031LF/HF,adjustedR2=0.129,P=0.027). CONCLUSION: A shift in sympathovagal balance toward parasympathetic predominance is associated with attenuation of portal hyperperfusion in a partial liver graft.

Fast numerical Fourier analysis of moiré pattern induced by a periodic metallic array on top of the microscopically patterned red-green-blue light sources.

An accurate and fast moiré pattern analysis algorithm is proposed for a periodic metallic array placed adjacent to a patterned red-green-blue (RGB) light source with a microscopic gap utilizing Fourier transform along with the human eye contrast sensitivity function. We analyzed how the moiré pattern evolved varying tilt angles and metal array periodicities placed on the top of RGB light sources, which have their own spatial periodicities. Based on multiplicative model, moiré patterns were numerically generated and the influences of 70 tilt angles and 60 periodicities on the moiré standard deviation were thoroughly analyzed to minimize moiré visibility. Our numerical results were compared to a prior analytical approach to obtain a good agreement, and the proposed scheme can be further applied to larger scale display systems with sophisticated touch screen metal arrays.

Simplified Unification Patch Venoplasty for Anomalous Portal Vein Branching in Living Donor Liver Transplantation With Right Lobe Graft.

Double portal vein (PV) branches during living donor liver transplantation (LDLT) with right lobe grafts have been considered challenging both in terms of donor safety and the complexity of vascular reconstruction in the recipient. Herein, we describe our experience with 24 adult LDLT recipients during which we employed unification patch venoplasty to reconstruct right lobe grafts with double PV orifices. We retrospectively reviewed the outcomes of 195 adult LDLT recipients receiving right lobe grafts, including 24 cases of adult LDLT recipients in which unification patch venoplasty was used to treat double PVs from January 2010 to June 2015. The anomalous portal vein branches of the donors were of type II in 7 cases (29.2%), type III in 15 cases (62.5%), and type IV in 2 cases (8.3%). We used propensity score matching analysis to compare the clinical outcomes of these recipients with those of 59 recipients who underwent adult LDLT using right lobe grafts with normal PVs in the same period. Intraoperative PV stenting was necessary in 2 (8.3%) of the 24 recipients undergoing unification patch venoplasty. During the follow-up period, all PVs remained patent until death or censoring. No significant difference in terms of postoperative vascular complications was evident between the 2 groups. Moreover, no major complications requiring reoperation or endoscopic and/or radiologic intervention developed in any of the 24 living donors with double PVs. In conclusion, our simplified unification patch venoplasty could be safe and feasible when used to reconstruct double PV orifices in right lobe LDLT from donors with complex PV anomalies.

ATP triggers a robust intracellular [Ca2+ ]-mediated signalling pathway in human synovial fibroblasts.

NEW FINDINGS: What is the central question of this study? What are the main [Ca2+ ]i signalling pathways activated by ATP in human synovial fibroblasts? What is the main finding and its importance? In human synovial fibroblasts ATP acts through a linked G-protein (Gq ) and phospholipase C signalling mechanism to produce IP3 , which then markedly enhances release of Ca2+ from the endoplasmic reticulum. These results provide new information for the detection of early pathophysiology of arthritis. ABSTRACT: In human articular joints, synovial fibroblasts (HSFs) have essential physiological functions that include synthesis and secretion of components of the extracellular matrix and essential articular joint lubricants, as well as release of paracrine substances such as ATP. Although the molecular and cellular processes that lead to a rheumatoid arthritis (RA) phenotype are not fully understood, HSF cells exhibit significant changes during this disease progression. The effects of ATP on HSFs were studied by monitoring changes in intracellular Ca2+ ([Ca2+ ]i ), and measuring electrophysiological properties. ATP application to HSF cell populations that had been enzymatically released from 2-D cell culture revealed that ATP (10-100 µm), or its analogues UTP or ADP, consistently produced a large transient increase in [Ca2+ ]i . These changes (i) were initiated by activation of the P2 Y purinergic receptor family, (ii) required Gq -mediated signal transduction, (iii) did not involve a transmembrane Ca2+ influx, but instead (iv) arose almost entirely from activation of endoplasmic reticulum (ER)-localized inositol 1,4,5-trisphosphate (IP3 ) receptors that triggered Ca2+ release from the ER. Corresponding single cell electrophysiological studies revealed that these ATP effects (i) were insensitive to [Ca2+ ]o removal, (ii) involved an IP3 -mediated intracellular Ca2+ release process, and (iii) strongly turned on Ca2+ -activated K+ current(s) that significantly hyperpolarized these cells. Application of histamine produced very similar effects in these HSF cells. Since ATP is a known paracrine agonist and histamine is released early in the inflammatory response, these findings may contribute to identification of early steps/defects in the initiation and progression of RA.

The relationship between clinical characteristics including presence of exposed lesions and health-related quality of life (HRQoL) in patients with psoriasis: analysis from the nationwide epidemiologic study for psoriasis in Korea (EPI-PSODE study).

BACKGROUND: Psychological aspect and quality of life should be considered in treating patients with psoriasis. OBJECTIVE: We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the Psoriatic Arthritis (PsA) Screening and Evaluation (PASE), Dermatology Life Quality Index (DLQI), MOS 36-Item Short-Form Health Survey (SF-36), Work Productivity and Activity Impairment Questionnaire Psoriasis (WPAI: PSO) and Medication Satisfaction Questionnaire (MSQ). RESULTS: Patients with a DLQI score > 5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA) and had higher PASE scores than patients with DLQI ≤ 5 (n = 266). The group of patients with exposed lesions (n = 871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n = 389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental). CONCLUSION: The presence of exposed lesions has a negative impact on quality of life, mental health and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.

Validity of the intra-operative measurement of stem anteversion and factors for the erroneous estimation in cementless total hip arthroplasty using postero-lateral approach.

BACKGROUND: Intra-operative estimation of stem anteversion in total hip arthroplasty (THA) using postero-lateral approach is made by the surgeon's visual assessment, using the tibia as a guide, with the assumption that tibial axis is vertical to the trans-epicondylar axis. However, the accuracy of the intra-operative estimation has rarely been verified with postoperative CT-scans, with controversies regarding these measurements particularly in case of knee osteoarthritis. Therefore we performed a prospective study to: (1) determine the accuracy of the intra-operative measurement and (2) investigate factors affecting the discrepancy between the surgeon's estimation and the real stem anteversion. HYPOTHESIS: Intra-operative estimation of stem anteversion correlated with the real stem anteversion on CT-scan. PATIENTS AND METHODS: Sixty-seven THAs using cementless straight stems (65 patients) without ipsilateral total knee arthroplasty were prospectively evaluated to compare the intra-operative measurement of stem anteversion with the real stem anteversion on computed tomography (CT) scans. There were 33 men and 34 women with a mean age of 59.7years (range, 27-84years) at the time of surgery. Age, tibia plateau angle, native femoral anteversion, femoro-tibial angle, body mass index, operative site, gender, coronal and sagittal tilt of the stem, stem type, ipsilateral knee osteoarthritis, and preoperative diagnosis were analyzed to evaluate the factors affecting the discrepancy between the intra-operative and CT measurements. RESULTS: The intra-operative estimation (mean, 21.5°±8.5°; range, 5.0°-39.0°) was greater than the CT measurement (mean, 19.5°±8.7°; range, 4.5°-38.5°) by 2.0°. The mean absolute value of discrepancy was 4.5°. The correlation coefficient between intra-operative and CT measurements was 0.837. The femoro-tibial angle was associated with the discrepancy between the two measurements. In the presence of genu varum deformity, the intra-operative measurement underestimated the stem anteversion. DISCUSSION: Although intra-operative estimation of stem anteversion was slightly greater than the real stem anteversion, there was an excellent correlation between the two. The femoro-tibial angle should be considered to optimize the stem anteversion during cementless THA using postero-lateral approach. LEVEL OF EVIDENCE: Level III, prospective case control study.

Aberrant GATA2 epigenetic dysregulation induces a GATA2/GATA6 switch in human gastric cancer.

Six GATA transcription factors play important roles in eukaryotic development. Among these, GATA2, an essential factor for the hematopoietic cell lineage, exhibits low expression in human gastric tissues, whereas GATA6, which is crucial for gastrointestinal development and differentiation, is frequently amplified and/or overexpressed in human gastric cancer. Interestingly, we found that GATA6 was overexpressed in human gastric cancer cells only when GATA2 expression was completely absent, thereby showing an inverse correlation between GATA2 and GATA6. In gastric cancer cells that express high GATA6 levels, a GATA2 CpG island is hypermethylated, repressing expression in these cells. In contrast, GATA6 expression is undetectable in GATA2-overexpressing gastric cancer cells, which lack GATA2 DNA methylation. Furthermore, PRC2 complex-mediated transcriptional silencing of GATA6 was observed in the GATA2-overexpressing cells. We also show that the GATA2 and PRC2 complexes are enriched within the GATA6 locus, and that the recruitment of the PRC2 complex is impaired by disrupting GATA2 expression, resulting in GATA6 upregulation. In addition, ectopic GATA2 expression significantly downregulates GATA6 expression, suggesting GATA2 directly represses GATA6. Furthermore, GATA6 downregulation showed antitumor activity by inducing growth arrest. Finally, we show that aberrant GATA2 methylation occurs early during the multistep process of gastric carcinogenesis regardless of Helicobacter pylori infection. Taken together, GATA2 dysregulation by epigenetic modification is associated with unfavorable phenotypes in human gastric cancer cells by allowing GATA6 expression.

Non-local means filter denoising for DEXA images.

Dual high and low energy images of Dual Energy X-ray Absorptiometry (DEXA) suffer from noises due to the use of weak amount of X-rays. Denoising these DEXA images could be a key process to enhance and improve a Bone Mineral Density (BMD) map which is derived from a pair of high and low energy images. This could further improve the accuracy of diagnosis of bone fractures, osteoporosis, and etc. In this paper, we present a denoising technique for dual high and low energy images of DEXA via non-local means filter (NLMF). The noise of dual DEXA images is modeled based on both source and detector noises of a DEXA system. Then, the parameters of the proposed NLMF are optimized for denoising utilizing the experimental data from uniform phantoms. The optimized NLMF is tested and verified with the DEXA images of the uniform phantoms and real human spine. The quantitative evaluation shows the improvement of Signal-to-Noise Ratio (SNR) for the high and low phantom images on the order of 30.36% and 27.02% and for the high and low real spine images on the order of 22.28% and 33.43%, respectively. Our work suggests that denoising via NLMF could be a key preprocessing process for clinical DEXA imaging.

Detection and classification of the breast abnormalities in digital mammograms via regional Convolutional Neural Network.

Automatic detection and classification of the masses in mammograms are still a big challenge and play a crucial role to assist radiologists for accurate diagnosis. In this paper, we propose a novel computer-aided diagnose (CAD) system based on one of the regional deep learning techniques: a ROI-based Convolutional Neural Network (CNN) which is called You Only Look Once (YOLO). Our proposed YOLO-based CAD system contains four main stages: mammograms preprocessing, feature extraction utilizing multi convolutional deep layers, mass detection with confidence model, and finally mass classification using fully connected neural network (FC-NN). A set of training mammograms with the information of ROI masses and their types are used to train YOLO. The trained YOLO-based CAD system detects the masses and classifies their types into benign or malignant. Our results show that the proposed YOLO-based CAD system detects the mass location with an overall accuracy of 96.33%. The system also distinguishes between benign and malignant lesions with an overall accuracy of 85.52%. Our proposed system seems to be feasible as a CAD system capable of detection and classification at the same time. It also overcomes some challenging breast cancer cases such as the mass existing in the pectoral muscles or dense regions.

Gq-activated fibroblasts induce cardiomyocyte action potential prolongation and automaticity in a three-dimensional microtissue environment.

Cardiac fibroblasts (CFs) are known to regulate cardiomyocyte (CM) function in vivo and in two-dimensional in vitro cultures. This study examined the effect of CF activation on the regulation of CM electrical activity in a three-dimensional (3-D) microtissue environment. Using a scaffold-free 3-D platform with interspersed neonatal rat ventricular CMs and CFs, Gq-mediated signaling was selectively enhanced in CFs by Gαq adenoviral infection before coseeding with CMs in nonadhesive hydrogels. After 3 days, the microtissues were analyzed by signaling assay, histological staining, quantitative PCR, Western blots, optical mapping with voltage- or Ca2+-sensitive dyes, and microelectrode recordings of CF resting membrane potential (RMPCF). Enhanced Gq signaling in CFs increased microtissue size and profibrotic and prohypertrophic markers. Expression of constitutively active Gαq in CFs prolonged CM action potential duration (by 33%) and rise time (by 31%), prolonged Ca2+ transient duration (by 98%) and rise time (by 65%), and caused abnormal electrical activity based on depolarization-induced automaticity. Constitutive Gq activation in CFs also depolarized RMPCF from -33 to -20 mV and increased connexin 43 and connexin 45 expression. Computational modeling confers that elevated RMPCF and increased cell-cell coupling between CMs and CFs in a 3-D environment could lead to automaticity. In conclusion, our data demonstrate that CF activation alone is capable of altering action potential and Ca2+ transient characteristics of CMs, leading to proarrhythmic electrical activity. Our results also emphasize the importance of a 3-D environment where cell-cell interactions are prevalent, underscoring that CF activation in 3-D tissue plays a significant role in modulating CM electrophysiology and arrhythmias.NEW & NOTEWORTHY In a three-dimensional microtissue model, which lowers baseline activation of cardiac fibroblasts but enables cell-cell, paracrine, and cell-extracellular matrix interactions, we demonstrate that selective cardiac fibroblast activation by enhanced Gq signaling, a pathophysiological trigger in the diseased heart, modulates cardiomyocyte electrical activity, leading to proarrhythmogenic automaticity.

Atypical subtrochanteric fractures in Korean hip fracture study.

In Korean, atypical subtrochanteric fractures (ASF) were rare. Higher BMI and use of bisphosphonate were significant risk factors of ASF. INTRODUCTION: Recently, ASF have been reported to increase among patients on bisphosphonate. However, the incidence of ASF and the association between ASF and bisphosphonate use have not been well defined in Asian population. Our purposes are (1) to estimate the proportion of ASF among Korean patients with proximal femur fracture and (2) to determine the associated risk factors of ASF in the Korean patients. METHODS: We conducted a multicenter (16 academic hospitals), prospective Korean hip fracture study on hip fracture in a cohort of patients aged 50 years or older from South Korea between July 2014 and May 2016. As a part of Korean hip fracture study, primary analysis examined the proportion of ASF among proximal femur fracture. To identify ASF, according to the definition by ASBMR task force, all radiographs of subtrochanteric fracture were reviewed. Associated risk factors for occurrence of ASF were also evaluated by using multivariable logistic regression analysis. RESULTS: Among 1361 patients with proximal femoral fractures due to low-energy trauma, 17 fractures (1.2%) were identified as ASF. Higher BMI and use of bisphosphonate before injury were independent risk factors of ASF. CONCLUSION: In Korean, ASF were rare. Higher BMI and use of bisphosphonate were significant risk factors of ASF.

Long-term effect of aromatase inhibitors on bone microarchitecture and macroarchitecture in non-osteoporotic postmenopausal women with breast cancer.

In non-osteoporotic postmenopausal women with breast cancer, aromatase inhibitors (AIs) negatively affected bone mineral density (BMD), lumbar spine trabecular bone score (TBS) as a bone microarchitecture index, and hip geometry as a bone macroarchitecture index. INTRODUCTION: AIs increase the risk of fracture in patients with breast cancer. Therefore, we aimed to evaluate the long-term skeletal effects of AIs in postmenopausal women with primary breast cancer. METHODS: We performed a retrospective longitudinal observational study in non-osteoporotic patients with breast cancer who were treated with AIs for ≥3 years (T-score >-2.5). Patients with previous anti-osteoporosis treatment or those who were given bisphosphonate during AI treatment were excluded from the analysis. We serially assessed BMD, lumbar spine TBS, and hip geometry using dual-energy X-ray absorptiometry. RESULTS: BMD significantly decreased from baseline to 5 years at the lumbar spine (-6.15%), femur neck (-7.12%), and total hip (-6.35%). Lumbar spine TBS also significantly decreased from baseline to 5 years (-2.12%); this change remained significant after adjusting for lumbar spine BMD. The annual loss of lumbar spine BMD and TBS slowed after 3 and 1 year of treatment, respectively, although there was a relatively constant loss of BMD at the femur neck and total hip for up to 4 years. The cross-sectional area, cross-sectional moment of inertia, minimal neck width, femur strength index, and section modulus significantly decreased, although the buckling ratio increased over the treatment period (all P < 0.001); these changes were independent of total hip BMD. CONCLUSIONS: Long-term adjuvant AI treatment negatively influenced bone quality in addition to BMD in patients with breast cancer. This study suggests that early monitoring and management are needed in non-osteoporotic patients with breast cancer who are starting AIs.

Optimal maintenance treatment with calcipotriol/betamethasone dipropionate gel in Korean patients with psoriasis vulgaris: a multicentre randomized, controlled clinical trial.

BACKGROUND: There is a lack of response data for topical treatments for psoriasis vulgaris in Asian patients. OBJECTIVES: To determine the optimal maintenance regimen for topical treatment with calcipotriol monohydrate/betamethasone dipropionate gel in Korean patients with psoriasis vulgaris, by comparing the efficacy of three 8-week maintenance regimens. METHODS: This was a multicentre, prospective, randomized, controlled, parallel-group, open-label, phase 4 clinical trial, conducted in South Korea. Patients with psoriasis vulgaris on the limbs/trunk received once-daily treatment with calcipotriol monohydrate (50 µg/g)/betamethasone dipropionate (500 µg/g) gel for 8 weeks (induction phase). Responders (defined as an Investigator's Global Assessment of Disease Severity (IGA) grade of 'clear' or 'almost clear') were then randomized to receive 8 weeks' maintenance treatment with Xamiol® gel once daily as needed [pro re nata (PRN Group)], once daily every day (Continuous group), or twice weekly - on Saturday and Sunday (Weekend group). The primary endpoint was the percentage of IGA responders at week 16. RESULTS: At the end of the induction phase, 62.18% of patients were IGA responders. At the end of the maintenance phase (week 16), the responder rate was 63.89% for the PRN group, 67.5% for the Continuous group and 31.43% for the Weekend group. The PRN and Continuous groups were statistically superior to the Weekend group (P = 0.0109 and P = 0.0015), but the PRN and Continuous groups did not differ statistically. The incidence of adverse events did not differ significantly between the groups. CONCLUSION: Among Korean patients with psoriasis vulgaris, maintenance treatment with calcipotriol monohydrate/betamethasone dipropionate using a continuous daily regimen or an 'as needed' daily regimen provided similar efficacy, whereas a twice-weekly regimen was significantly less efficacious than either of these regimens.

Epigenetic alterations of the BDNF gene in combat-related post-traumatic stress disorder.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) plays a crucial role in modulating resilience and vulnerability to stress. The aim of this study was to investigate whether epigenetic regulation of the BDNF gene is a biomarker of post-traumatic stress disorder (PTSD) development among veterans exposed to combat in the Vietnam War. METHODS: Using the Clinician-Administered PTSD Scale, combat veterans were grouped into those with (n = 126) and without (n = 122) PTSD. DNA methylation levels at four CpG sites within the BDNF promoter I region were quantified in the peripheral blood using pyrosequencing. The effects of BDNF DNA methylation levels and clinical variables on the diagnosis of PTSD were tested using binary logistic regression analysis. RESULTS: Subjects with PTSD showed a higher DNA methylation of four CpG sites at the BDNF promoter compared with those without PTSD. High methylation levels at the BDNF promoter CpG site, high combat exposure, and alcohol problems were significantly associated with PTSD diagnosis. CONCLUSIONS: This study demonstrated an association between higher DNA methylation of the BDNF promoter and PTSD diagnosis in combat-exposed individuals. Our findings suggest that altered BDNF methylation may be a valuable biomarker of PTSD after trauma exposure.