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To date, there is controversy regarding unilateral versus bilateral stent placement in patients with malignant hilar biliary strictures (MHBSs). The aim of this study was to compare the clinical outcomes and complications of unilateral and bilateral (stent-in-stent method) stent placements for these patients.We conducted a multicenter retrospective analysis of patients with inoperable MHBS who underwent endoscopic self-expandable metal stent (SEMS) placement from January 2009 to December 2019. Two groups classified according to the stent procedure method were compared for demographic, procedural, and postprocedure factors. Survival analysis for patency loss and overall survival was also conducted.A total of 236 subjects were included. A superior technical success rate was found in the unilateral stent group (98.8% vs. 82.5%, P0.001), whereas the clinical success rate was higher in the bilateral group (85.7% vs. 70.5%, P = 0.028). There was no significant difference with respect to complications or patency loss, and the bilateral group had better overall survival (P0.01). In the Cox proportional hazard model, MHBSs from lymph node compression were associated with a higher risk of death (HR = 9.803, P = 0.003). In contrast, bilateral SEMS insertion showed reduced postprocedural mortality (HR = 0.316, P = 0.001).Y-type stent-in-stent bilateral SEMSs are technically difficult but demonstrated more favorable overall survival for palliative bile drainage of inoperable MHBS patients compared to unilateral insertions.

Objective: This study investigated the efficacy of using Nokyonggunbi-tang and other Korean medical treatments for a patient with consumptive disease and chronic fatigue.Methods: A 59-year-old female patient with fatigue, headache, dizziness, and neck pain due to consumptive disease and chronic fatigue was treated with herbal medicine (Nokyonggunbi-tang), together with acupuncture, pharmacopuncture, cupping, and chuna manual therapy, for 22 days. The treatment effects on the pain were evaluated using the scores for the Fatigue Severity Scale (FSS), European Quality of Life Five Dimensions (EQ-5d) Scale, Neck Disability Index (NDI), and Numerical Rating Scale (NRS).Results: Following treatment, the patient showed a decrease in the FSS, NDI, and NRS scores and an improvement in the EQ-5d score.Conclusions: Nokyonggunbi-tang and Korean medical treatment significantly improved fatigue symptoms in a patient with no substrate disease.

Background The rates of very elderly patients (≥85 years old) undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) are rapidly increasing. They are under-represented in clinical trials, and those who are included may not reflect the real-world population. We aim to review the clinical characteristics of very elderly patients undergoing PCI for ACS and identify factors associated with adverse outcomes. Method All very elderly patients undergoing PCI for ACS in the Auckland region between January 2014 to December 2016 were included. Baseline clinical and procedural details were obtained, and the primary endpoint was all-cause mortality measured up to a maximum of 4 years. Secondary endpoints include recurrent myocardial infarction, unplanned revascularisation, stroke and major bleeding. Results A total of 186 patients were included for analysis (mean age 87.6±2.8 years, 51.6% male). Indications for PCI were ST-elevation myocardial infarction (STEMI) in 74 (39.8%), non-ST elevation myocardial infarction (NSTEMI) in 97 (52.2%) and unstable angina in 15 patients (8.1%). Successful PCI was completed in 180 patients. At a maximal follow-up of 4 years (mean 23.4 mo), the rates of all-cause mortality and recurrent myocardial infarction were 22.0% and 14.0% respectively. The risk of mortality was increased by the presence of diabetes (44.8% vs 17.8%, HR=3.0, 95%CI: 1.6–5.9, p=0.001), STEMI (33.8% vs 13.5%, HR=3.1, 95%CI: 1.6–5.9, p=0.001), and reduced eGFR (every -10 mL/min/1.73m2, HR=1.7, 95%CI: 1.3–2.1, p Conclusion Very elderly patients who undergo PCI for ACS have acceptable survival outcomes. STEMI, diabetes and impaired renal function were predictive of mortality in this elderly cohort.

Background The purpose of the present study was to investigate the effectiveness of using the computed tomography (CT) capsular sign with lipohemarthrosis of the hip joint as a selective indicator for preoperative magnetic resonance imaging (MRI) of the hip or prophylactic fixation of the ipsilateral femoral neck for the prevention of unplanned surgery due to delayed diagnosis of occult ipsilateral femoral neck fractures in patients with high-energy femoral shaft fractures. Methods We evaluated the CT capsular sign with lipohemarthrosis in patients with a high-energy femoral shaft fracture without a preoperative diagnosis of an ipsilateral femoral neck fracture. The CT capsular sign with lipohemarthrosis was considered positive when the side-to-side difference in anterior capsular distension was >1 mm and lipohemarthrosis was seen on soft-tissue-window CT images. A positive CT capsular sign with lipohemarthrosis prompts preoperative hip MRI or prophylactic femoral neck fixation with a reconstruction nail. Results One hundred and fifty-six consecutive patients were included. Eight patients were preoperatively diagnosed with a displaced or hairline ipsilateral femoral neck fracture, whereas the remaining 148 patients showed no ipsilateral femoral neck fracture on radiographs and bone-window CT images. On soft-tissue-window CT images, 29 (19.6%) of the 148 patients had a positive CT capsular sign with lipohemarthrosis. We performed preoperative MRI for 3 patients; in the remaining 26 patients, prophylactic femoral neck fixation was performed with a reconstruction nail. We identified 5 occult ipsilateral femoral neck fractures among the 29 patients with a positive sign: 2 on preoperative MRI scans, 2 on immediate postoperative radiographs, and 1 on radiographs made 6 weeks postoperatively. In 119 patients with a negative sign, no occult ipsilateral femoral neck fracture was identified. All occult ipsilateral femoral neck fractures healed without further displacement of the femoral neck. Consequently, additional unplanned surgery for delayed diagnosis of occult ipsilateral femoral neck fracture was not required. Conclusions The use of the CT capsular sign with lipohemarthrosis as a selective indicator for preoperative hip MRI or prophylactic femoral neck fixation with a reconstruction nail in patients with high-energy femoral shaft fractures is effective for preventing unplanned surgery due to delayed diagnosis of occult ipsilateral femoral neck fractures. Level of evidence Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Choledochocele is the least common type of choledochal cyst. Choledochocele has a potential for carcinogenesis, but only a handful of cases with concurrent ampullary carcinoma have been reported. We recently experienced a case of choledochocele with tubulovillous adenoma with focal high-grade dysplasia, which was successfully and completely resected en bloc via endoscopic papillectomy. Prior to endoscopic papillectomy, the endoscopic ultrasonography was able to accurately diagnose the ampullary tumor arising in choledochocele. Herein, we would like to report this case and discuss the potential of malignant transformation and the usefulness of endoscopic ultrasonography in choledochocele.

Aim We scrutinised the computed tomography (CT) capsular sign, which refers to the anterior capsular distension of the hip, to determine whether we can use it as an additional clue for detecting occult ipsilateral femoral neck fracture (IFNF) before operation. Patients and Methods We retrospectively examined 79 patients who suffered high-energy femoral shaft fracture and were evaluated with preoperative CT for occult IFNF. The occult IFNF was defined as a fracture that was not diagnosed confirmatively during preoperative evaluation. Thirteen patients were included in the occult IFNF group and 66 were included in the femoral neck intact group. A side-to-side difference of more than 1 mm of capsular distension was considered a positive CT capsular sign. Results Among 13 patients in the occult IFNF group, 6 had a hairline fracture (bony window images) and 12 had a positive CT capsular sign (soft tissue window images) on preoperative CT scans. The presence of IFNF was more significantly associated with the CT capsular sign than with the hairline fracture (p = 0.031). Among the 66 patients in the femoral neck intact group, the CT capsular sign was false positive in 4. Conclusion The CT capsular sign can be used to detect the presence of occult IFNF in high-energy trauma patients with femoral shaft fractures. During the preoperative evaluation of IFNF, surgeons must pay extra attention to the presence of occult IFNF when the CT capsular sign is positive.

A new type of hydrogels based on poly(styrene-alt-maleic anhydride) (PSMA) was prepared via Diels-Alder click chemistry. The formulations consisting of tetrazine-functionalized PSMA as a multi-clickable polymer and norbornene-terminated poly(ethylene glycol) (PEG) as a polymeric cross-linker were used as precursors to give ultrafast hydrogels with controlled structures. The hydrogels formed within several minutes under a physiological condition without any catalyst, and their storage modulus (G′) values were in the range 0.3–1.7 kPa suitable for bio-applications. The pore structure and the release profile of doxorubicin hydrochloride (DOX・HCl) of the hydrogels could be manipulated by the molecular weight of PEG. The precursors exhibited practically no depressing effect of the normal HEK293 growth, while the DOX・HCl-loaded hydrogel presented significant anticancer activity towards HeLa cells. The results suggested this biocompatible hydrogel as a potential injectable drug depot for tumor sites.

Objective The aim of this study was to investigate the effects of eupatilin on protein kinase D1 (PKD1) and nuclear factor kappa B (NF-κB) signaling pathways in cerulein-induced in vitro pancreatitis. Methods We used collagenase digestion to isolate pancreatic acinar cells from male C57BL/6 mice. In vitro acute pancreatitis was induced by treatment with a supramaximal dose of cerulein. Eupatilin was pretreated before stimulation with cerulein. Results Eupatilin significantly reduced cerulein-induced amylase release in pancreatic acini. Eupatilin treatment downregulated cerulein-induced expression of interleukin (IL)-1β, IL-6, and CC chemokine ligands 2 and 5, but it upregulated expression of IL-4 and IL-10. We demonstrated that eupatilin pretreatment attenuated cerulein-induced necrosis in isolated pancreatic acinar cells. This effect of eupatilin was confirmed by lactic dehydrogenase assay, fluorescence-activated cell sorting analysis, and cytopathologic analysis. Eupatilin inhibited cerulein-induced activation of PKD1/NF-κB and the nuclear translocation of NF-κB. Conclusions Our data demonstrated that eupatilin is a potential therapeutic candidate for the treatment of pancreatitis through its ability to reduce cellular necrosis and inflammatory responses by inhibition of the PKD1/NF-κB signaling pathway.

Background: Developing personalized strategies for cancer has shown good efficacies. Methods: We assessed the molecular targets programmed death ligand 1 (PD-L1), microsatellite instability (MSI), and PIK3CA. Seventy-four patients with liposarcomas who underwent curative resection were assessed for PD-L1 expression in the tumor and tumor-infiltrating lymphocytes (TILs), mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry, MSI using polymerase chain reaction, and PIK3CA mutation/amplification using pyrosequencing and fluorescence in situ hybridization. Results: Seventeen (23%) cases were TIL+ (≥1 + expression) and associated with longer 5-year overall survival than those with TIL– tumors (84.4 vs. 60.8%, p = 0.007). Six (35.3%) PD-L1+ tumors were detected only in TIL+ cases, with none detected in tumor cells. Two well-differentiated liposarcomas showed MSI, one low and one high with concurrent loss of MLH1, MSH6, and PMS2. PIK3CA mutation was detected in 7 (9.5%) [exon 9 (n = 4) and exon 20 (n = 3)] and only 1 Q546K mutation was a PD-L1+ tumor. PIK3CA copy number gain was detected in 18 (24.4%) and was associated with TIL+ tumors (p = 0.045). Conclusions: Our comprehensive immuno-molecular panel suggests that liposarcoma should be categorized based on the molecular genomic subtype for precision medicine.

Objectives: Hereditary elliptocytosis (HE) is inherited in an autosomal dominant fashion, and the majority of HE-associated defects occur due to qualitative and quantitative defects in the RBC memb...

Public interventions have shown to optimize the use of antibiotics in children with acute otitis media (AOM). In this study, we describe the AOM-related antibiotic use among children in South Korea using national cohort data. We retrieved the Health Insurance Review & Assessment Service data to construct a national cohort of children aged 0–6 years who had been diagnosed with AOM between 2012 and 2018. Of 25,212,264 children included, the antibiotic prescription has increased for amoxicillin/amoxicillin-clavulanate from 56.1% in 2012 to 61.8% in 2018. Prescription has decreased for cephalosporin (35.1% in 2012 to 31.8% in 2018) and macrolide (8.7% in 2012 to 6.4% in 2018). National cohort data have shown an increased trend in AOM-related aminopenicillin prescription and downward trend cephalosporin and macrolide use in South Korea. A multi-faceted approach is required to control the antimicrobial resistance at a population level., Graphical Abstract

Background: About 10% of patients with gallbladder (GB) stones also have concurrent common bile duct (CBD) stones. Laparoscopic cholecystectomy (LC) after removal of CBD stones using endoscopic retrograde cholangiopancreatography (ERCP) is the most widely used method for treating coexisting gallbladder and common bile duct stones. We evaluated the optimal timing of LC after ERCP according to clinical factors, focusing on preoperative relief of jaundice. Methods: A total of 281 patients who underwent elective LC after ERCP because of choledocholithiasis and cholecystolithiasis from January 2010 to April 2018 were retrospectively reviewed. We compared the hospital stay, perioperative morbidity, and rate of surgical conversion to open cholecystectomy according to the relief of jaundice before surgery. These enrolled patients were divided into two groups: relief of jaundice before surgery (group 1, n = 125) or not (group 2, n = 156). Results: The initial total bilirubin level was higher in group 1, however, there were no significant differences in the other baseline characteristics including age, sex, American Society of Anesthesiologists score, previous surgical history, white blood cell count, C-reactive protein, and operative time between the two groups. There was also no significant difference in postoperative hospital stay between the two groups (4.5 ± 3.3 vs. 5.5 ± 5.6 days, p = 0.087). However, after ERCP, the waiting time until LC was significantly longer in group 1 (5.0 ± 4.9 vs. 3.5 ± 2.4 days, p &lt, 0.001). There were no statistical differences in the conversion rate (3.2% vs. 3.8%, p = 0.518) or perioperative morbidity (4.0% vs. 5.8%, p = 0.348), either. Conclusions: LC would not be delayed until the relief of jaundice after ERCP since there were no significant differences in perioperative morbidity or surgical conversion rate to open cholecystectomy. Early LC after ERCP may be feasible and safe in patients with cholangitis and cholecystolithiasis.

Impact of increased osteoporosis diagnosis and treatment among postmenopausal women (PMW) on reduction in fractures and associated costs in Japan from 2020 to 2040 was modeled. Japan is currently home to the world’s oldest population and the 65 + years demographic is expected to grow to 35% by 2040. Thus, identifying strategies to reduce clinical and economic burden associated with osteoporosis among this at-risk population is critical. A microsimulation model was developed to project osteoporotic annual fracture incidence and costs among PMW 2020–2040. Fracture risk was estimated using a simplified Fracture Risk Assessment Tool (FRAX). Fracture estimates were based on annualized FRAX risk and treatment impact. Published literature informed inputs for direct and indirect fracture costs, DXA screening costs, and treatment costs and efficacy. Japan’s current screening and treatment rates were compared against 50% increases to (1) case finding (screening rate and subsequent treatment rate) and (2) treatment rate among those at highest fracture risk. From 2020 to 2040, 21.6 million fractures are projected costing US $410.2 billion. Increased case finding scenario resulted in the prevention of 456.9 thousand primary and 340.9 thousand second + fractures saving US $4.25 billion. Increased treatment scenario led to 500.5 thousand and 435.5 thousand fewer primary and second + fractures, respectively, and reduced economic burden by $3.1 billion. Improvements to rates of osteoporosis screening and preventive treatment in Japan’s aging population through disease awareness campaigns and post-fracture care programs, among others, will likely reduce osteoporosis-associated clinical and economic burden.

Linear and nonlinear rheological properties of cellulose nanofiber (CNF) suspensions were measured under small and large amplitude oscillatory shear (SAOS and LAOS) flow. Four different CNFs were produced, two by only mechanical disintegration and two with chemical pretreatments. Linear viscoelastic properties distinguished chemically treated CNFs from two untreated fibers via a different scaling exponent of the elastic modulus. However, different mechanical fibrillation degree was not characterized via linear viscoelastic properties. In contrast, nonlinear viscoelastic properties reflected both effects of chemical pretreatments and mechanical fibrillation. More fibrillated CNFs exhibited nonlinear rheological phenomena at larger deformations. In addition, chemically treated CNFs exhibited greater network stiffness and higher network recovery rates due to the presence of charged functional groups on the fiber surfaces. A material-property co-plot showed that network stiffness and recovery rate were in a trade-off relationship.

The purpose of this study is to compare the acetabular teardrop (the structure located inferomedially in the acetabulum, just superior to the obturator foramen. The medial lip is the interior, and the lateral lip is the exterior of the acetabular wall) with the inferior acetabular rim as anatomical landmarks to measure the acetabular abduction angle (AAD) using coronal CT images from different levels. Our retrospective study included 120 pelvic CT scans from patients with non-orthopedic pathologies or stress fractures of the proximal femur. The patients included 60 females with a mean age of 48 years (range 40–66) and 60 males with a mean age of 46 years (range 38–65). Each AAD was measured using coronal plane CT slices from five levels: AAD (+ 10) (10 mm anterior to the femoral head center), AAD (+ 5) (5 mm anterior to the femoral head center), AAD (0) (through the femoral head center), AAD (− 5) (5 mm posterior to the femoral head center), and AAD (− 10) (10 mm posterior to the femoral head center). The measurements were then divided into two groups: teardrop-based AADs [AAD (+ 10), AAD (+ 5), and AAD (0)] and rim-based AADs [AAD (− 5) and AAD (− 10)]. There were no mean significant differences in AAD within the groups, whereas the difference between the groups was significant. The mean teardrop-based AAD was quite significantly different from the mean rim-based AAD due to the use of different anatomical landmarks. Teardrop-based AADs are lower than rim-based AADs, leading to measurement differences of more than 10°. AAD measurements considering the inferior acetabular rim can be more accurate than those considering the acetabular teardrop because the inferior rim represents the nearly hemispheric acetabulum better than does the teardrop. It is recommended to differentiate between the teardrop and the inferior acetabular rim when measuring AAD to avoid confusion regarding acetabular abduction.

Background and Objectives Although it is well known that hypoxic culture conditions enhance proliferation of human mesenchymal stem cells, the exact mechanism is not fully understood. In this study, we investigated the effect of fibroblast growth factor (FGF)-17 from hypoxic human Wharton’s Jelly-derived mesenchymal stem cells (hWJ-MSCs) on cell proliferation at late passages. Methods and Results hWJ-MSCs were cultured in α-MEM medium supplemented with 10% fetal bovine serum (FBS) in normoxic (21% O2) and hypoxic (1% O2) conditions. Protein antibody array was performed to analyze secretory proteins in conditioned medium from normoxic and hypoxic hWJ-MSCs at passage 10. Cell proliferation of hypoxic hWJ-MSCs was increased compared with normoxic hWJ-MSCs from passage 7 to 10, and expression of secretory FGF-17 was highly increased in conditioned medium from hypoxic hWJ-MSCs at passage 10. Knockdown of FGF-17 in hypoxic and normoxic hWJ-MSCs decreased cell proliferation, whereas treatment of hypoxic and normoxic hWJ-MSCs with recombinant protein FGF-17 increased their proliferation. Signal transduction of FGF-17 in hypoxic and normoxic hWJ-MSCs involved the ERK1/2 pathway. Cell phenotypes were not changed under either condition. Differentiation-related genes adiponectin, Runx2, and chondroadherin were downregulated in normoxic hWJ-MSCs treated with rFGF-17, and upregulated by siFGF-17. Expression of alkaline phosphatase (ALP), Runx2, and chondroadherin was upregulated in hypoxic hWJ-MSCs, and this effect was rescued by transfection with siFGF-17. Only chondroadherin was upregulated in hypoxic hWJ-MSCs with rFGF-17. Conclusions In hypoxic culture conditions, FGF-17 from hypoxic hWJ-MSCs contributes to the maintenance of high proliferation at late passages through the ERK1/2 pathway.

Measuring cortisol in hair has recently been established as a reliable physiological index to evaluate chronic stress conditions in humans and many animal species. The aim of this study was to determine serum cortisol and the concentrations of hair cortisol from various body sites of lactating Holstein cows and heifers during thermal comfort zone. Forty-seven multiparous lactating Holstein cows (average milk yield 37.5 ± 2.3 kgd−1, days in milk = 110 ± 47 days, body weight = 623 ± 75 kg) and 23 Holstein heifers (10-12 months of age, body weight = 258 ± 20 kg) were used in this study. Blood samples were collected on days (d) 0, 30, and 60 of the study. Hair samples were harvested from the forehead, withers, and rump sites of the animals. Data for temperature-humidity index (average THI = 69.3 ± 1.2) represented the threshold environmental conditions during the experiment. Serum cortisol concentration was higher on day 0 of the study and lower on day 30 and day 60 of sampling in lactating Holstein cows and heifers (P 0.05). Conclusions drawn indicate that the distribution of cortisol into the hair shaft does not depend on hair sampling sites, and so that of the hair cut for cortisol analysis can be collected from any of the three body sites.

This study investigates the anti-cancer effects of cervical cancer (HeLa) cells in a conditioned medium (CM) obtained from normoxic and hypoxic cultured human adult dermal fibroblasts (HDFs). The HeLa cells showed decreased cell viability, arrested cell cycles, and increased apoptosis in CM from hypoxic cultured HDFs (H-CM) compared with normoxic cultured HDFs (N-CM). In up-regulated (> 2-fold) proteins of H-CM compared with N-CM, the top enriched term of biological process of gene ontology (GO) was GO:0006955~immune response. In intracellular down-regulated (> 2-fold) proteins of HeLa cells treated with H-CM compared with N-CM, the top enriched term of biological process of GO was GO:0016579~protein deubiquitination, and the terms of the KEGG pathway were determined to be hsa05166:HTLV-I infection, hsa03410:base-excision repair, and hsa05340:primary immunodeficiency. Among down-regulated hub proteins with ≥ 5 edges (ESR1 MCL1, TBP, CD19, LCK, PCNA, CHEK1, and POLA1) of HeLa cells treated with H-CM, the top enriched term of biological process of GO and the KEGG pathway were GO:0006272~leading strand elongation and hsa05166:HTLV-I infection. H-CM displayed not only enhanced anti-cancer effects on HeLa cells compared with N-CM, but also induced intracellular signaling patterns with 9 hub proteins.

Introduction Severe valgus-impacted femoral neck fractures are associated with femoral neck shortening (FNS). However, no study has focused on the effect of reduction for severe valgus impaction in terms of healing and restoration of the femoral neck length. This study aimed to compare FNS and treatment outcomes of in situ fixation and fixation after reduction for severe valgus-impacted femoral neck fractures in patients aged 65 years or younger. Methods This retrospective study included 55 patients who underwent internal fixation with three parallel screws for femoral neck fractures with valgus impaction >15° (AO/OTA classification 31-B1.1) between January 2006 and December 2018. Twenty-eight and 27 patients underwent in situ fixation (in situ group) and fixation after reduction (reduction group), respectively. In the reduction group, reduction using lateral traction with a Schanz pin was performed before internal fixation. Complications such as fixation failure, non-union, and avascular necrosis (AVN), caput-collum-diaphysis (CCD) angle, posterior tilt angle, amount of FNS, and Harris Hip Score (HHS) were compared between the groups. Results Bone union was achieved in all patients; AVN occurred in two patients in each group. No significant difference was seen in the preoperative characteristics between the groups. The CCD angle at 1 year postoperatively was significantly different between the groups, whereas the posterior tilt angle at 1 year postoperatively was not different. FNS at 1 year postoperatively was significantly lower in the reduction group than in the in situ group. FNS by >5 mm was significantly less frequent in the reduction group than in the in situ group (11% versus 75%). The mean HHS at 1 year and 2 years postoperatively was significantly higher in the reduction group than in the in situ group. FNS and HHS were negatively correlated; the mean HHS was significantly higher in patients with none/mild shortening ( Conclusion In patients aged 65 years or younger, internal fixation after reduction for severe valgus-impacted femoral neck fractures is safe and effective for achieving successful bone union and restoring the femoral neck length.

The objective of the present study was to compare sex hormone-binding globulin (SHBG) levels according to sex (healthy male and female volunteers) and age to determine reference values. Serum SHBG expression levels in patients with breast cancer with different tumor burden states were also determined. A total of 109 samples were obtained from 34 patients in 3 different disease states (non-tumor, localized tumor and systemic metastasis) during follow-up. A sandwich ELISA was conducted to measure SHBG, cancer antigen (CA)15-3 and CA125 expression levels. Wilcoxon rank-sum tests were performed on non-normally distributed data and an unpaired t-test was used for normally distributed variables. SHBG expression levels were higher in females compared with males (P

Background Despite many reports on the diagnostic yield of cytology from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), inter-slide differences are unknown. This prospective study aimed to compare diagnostic yield and cellular characteristics of bottom slides (BS) and top slides (TS) from EUS-FNA cytology performed without an on-site cytopathologist. Methods In patients with suspected pancreatic cancer on previous imaging explorations, a single endoscopist performed EUS-FNA and obtained 2 sets of cytology slide (8 BS and 8 TS), 1 cellblock slide, and 1 biopsy slide. Both slide sets were randomly assigned. A cytopathologist with more than 10 years of expertise in pancreatic cytopathology blindly inspected and compared two slide sets. Results In total, 73 specimens [42 head (57.5%), 16 body (21.9%), and 15 tail (20.5%)] were acquired for final analysis. Seventy-one cases were finally diagnosed with pancreatic cancer. The sensitivity and specificity of BS were 80.3% and 100.0%; and of TS 78.9% and 100.0%, respectively. In analyzing inter-slide difference, 66 cases (90.4%) showed consistent results between BS and TS. However, seven (9.6%) were positive only in one slide sets (4 BS and 3 TS). The proportions of specimens more than moderate and high cellularity were 75.3% and 60.3% in both slide sets (P> 0.99), and the proportion of artifact-free sets were 50.7%, and 52.1% for the BS and TS, respectively (P= 0.869). Conclusions Although BS and TS exhibited highly consistent diagnostic yields in cytologic smears from EUS-FNA, the proportion of inter-slide discordance is clinically considerable. Both slide sets need to be examined if there is no on-site cytopathologist.

PURPOSE Melanoma is a highly heterogeneous neoplasm, composed of subpopulations of tumor cells with distinct molecular and biological phenotypes and genotypes. In this study, to determine the genetic heterogeneity between primary and metastatic melanoma in Korean melanoma patients, we evaluated several well-known genetic alterations of melanoma. In addition, to elucidate the clinical relevance of each genetic alteration and heterogeneity between primary and metastatic lesions, clinical features and patient outcome were collected. Materials and Methods In addition to clinical data, BRAF, NRAS, GNAQ/11 mutation and KIT amplification data was acquired from an archived primary Korean melanoma cohort (KMC) of 188 patients. Among these patients, 43 patients were included for investigation of tumor heterogeneity between primary melanoma and its corresponding metastatic lesions. RESULTS Overall incidence of genetic aberrations of the primary melanomas in KMC was 17.6% of BRAF V600, 12.6% of NRAS mutation, and 28.6% of KIT amplification. GNAQ/11 mutation was seen in 66.6% of the uveal melanoma patients. Patients with BRAF mutation were associated with advanced stage and correlated to poor prognosis (p < 0.01). Among 43 patients, 55.8% showed heterogeneity between primary and metastatic lesion. The frequency of BRAF mutation and KIT amplification significantly increased in the metastatic lesions compared to primary melanomas.

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.

BACKGROUND To assess the association between HLA-B57.01 (Human leukocyte antigen) and clinical parameters of chronic periodontitis in people living with HIV (PLWHIV). METHODS All patients were recruited from the HIVCENTER at the University Hospital Frankfurt during April 2014 and July 2015. Periodontal examination included Periodontal Screening Index (PSI), Gingivalindex (GI), Bleeding on Probing Index (BOP), Periodontal Probing Depth (PD), Clinical Attachment Level (CAL) and DMF-T Score (decayed, missing, filled teeth). Associations among periodontitis, HLA-system and additional risk factors in PLWHIV were evaluated in multivariate analyses. RESULTS One hundred PLWHIV were enrolled. Forty-five patients were naive, meaning that these patients never took antiretroviral (ARV) drugs before, 55 patients treated with combined antiretroviral therapy (cART). Nineteen patients presented a positive HLA-B 57.01 status. PLWHIV who were carriers of HLA-B 57.01 had significantly lower PSI-scores (Grade 3 or higher; 0/19 [0%] versus 16/41 [39%] versus 17/40 [42%]; p =

RATIONALE Emphysematous pancreatitis, a rare complication of acute necrotizing pancreatitis with a high mortality rate, is associated with gas-forming bacteria. When using the step-up approach for treating emphysematous pancreatitis, it is preferable to delay drainage interventions for 4 weeks. However, percutaneous drainage may be necessary, even in the early phase of acute pancreatitis, for a patient whose sepsis deteriorates despite optimal medical management. Percutaneous drainage can then be followed by endoscopic necrosectomy through the percutaneous tract. PATIENT CONCERNS A 52-year-old man was transferred to our hospital for treatment of sepsis and multiorgan failure associated with emphysematous pancreatitis. DIAGNOSIS An abdominal computed tomography scan had shown pancreatic and peripancreatic necrosis, along with extensive gas bubbles. INTERVENTIONS Despite optimal medical management, the patient's condition continued to deteriorate, and it became necessary to insert 2 percutaneous catheter drainages (PCDs), even though the patient was still in the early phase of pancreatitis. Each PCD was upsized and irrigated with sterile saline by an interventional radiologist twice a week. The infected necrosis around the tail of the pancreas was completely resolved after PCD. However, PCD through the transperitoneal route did not resolve necrosis around the pancreatic head. Following the PCDs, percutaneous pancreatic necrosectomy using an ultra-slim upper endoscope was performed, after which the patient recovered quickly and was discharged. OUTCOMES Follow-up computed tomography was performed 12 weeks after the patient was discharged, and it showed complete resolution of the walled-off necrosis. The patient's condition improved without any fluid collection or complications. LESSONS PCD can be used in the early phase of emphysematous pancreatitis for patients who continue to deteriorate due to sepsis. This can easily be followed, if necessary, by percutaneous pancreatic necrosectomy using an ultra-slim endoscope.

In this study, the effects of cone-plate (C/P) and parallel-plate (P/P) geometries were investigated on the rheological properties of various complex fluids, e.g. single-phase (polymer melts and solutions) and multiphase systems (polymer blend and nanocomposite, and suspension). Small amplitude oscillatory shear (SAOS) tests were carried out to compare linear rheological responses while nonlinear responses were compared using large amplitude oscillatory shear (LAOS) tests at different frequencies. Moreover, Fourier-transform (FT)-rheology method was used to analyze the nonlinear responses under LAOS flow. Experimental results were compared with predictions obtained by single-point correction and shear rate correction. For all systems, SAOS data measured by C/P and P/P coincide with each other, but results showed discordance between C/P and P/P measurements in the nonlinear regime. For all systems except xanthan gum solutions, first-harmonic moduli were corrected using a single horizontal shift factor, whereas FT rheology-based nonlinear parameters (I3/1, I5/1, Q3, and Q5) were corrected using vertical shift factors that are well predicted by single-point correction. Xanthan gum solutions exhibited anomalous corrections. Their first-harmonic Fourier moduli were superposed using a horizontal shift factor predicted by shear rate correction applicable to highly shear thinning fluids. The distinguished corrections were observed for FT rheology-based nonlinear parameters. I3/1 and I5/1 were superposed by horizontal shifts, while the other systems displayed vertical shifts of I3/1 and I5/1. Q3 and Q5 of xanthan gum solutions were corrected using both horizontal and vertical shift factors. In particular, the obtained vertical shift factors for Q3 and Q5 were twice as large as predictions made by single-point correction. Such larger values are rationalized by the definitions of Q3 and Q5. These results highlight the significance of horizontal shift corrections in nonlinear oscillatory shear data.

Mesenchymal stem cells (MSCs) have been considered an alternative source of neuronal lineage cells, which are difficult to isolate from brain and expand in vitro. Previous studies have reported that MSCs expressing Nestin (Nestin+ MSCs), a neuronal stem/progenitor cell marker, exhibit increased transcriptional levels of neural development-related genes, indicating that Nestin+ MSCs may exert potential with neurogenic differentiation. Accordingly, we investigated the effects of the presence of Nestin+ MSCs in bone-marrow-derived primary cells (BMPCs) on enhanced neurogenic differentiation of BMPCs by identifying the presence of Nestin+ MSCs in uncultured and cultured BMPCs. The percentage of Nestin+ MSCs in BMPCs was measured per passage by double staining with Nestin and CD90, an MSC marker. The efficiency of neurogenic differentiation was compared among passages, revealing the highest and lowest yields of Nestin+ MSCs. The presence of Nestin+ MSCs was identified in BMPCs before in vitro culture, and the highest and lowest percentages of Nestin+ MSCs in BMPCs was observed at the third (P3) and fifth passages (P5). Moreover, significantly the higher efficiency of differentiation into neurons, oligodendrocyte precursor cells and astrocytes was detected in BMPCs at P3, compared with P5. In conclusion, these results demonstrate that neurogenic differentiation can be enhanced by increasing the proportion of Nestin+ MSCs in cultured BMPCs.

Background/Aims In inflammatory bowel disease (IBD), repeated bouts of remission and relapse occur in patients and can impose a risk of colitis-associated cancer. We hypothesized that plant extracts of Atractylodes macrocephala (AM) or Taraxacum herba (TH) may be better than sulfasalazine for treating this disease because these extracts can promote additional regeneration. Methods Murine intestinal epithelial IEC-6 cells were pretreated with AM or TH before a lipopolysaccharide (LPS)-induced challenge. Acute colitis was induced with 7 days of dextran sulfate sodium (DSS) in male C57BL/6 mice, and extracts of AM and TH were administered for 2 weeks before DSS administration. Results In vitro studies demonstrated that AM or TH treatment reduced LPS-induced COX-2 and tumor necrosis factor-α mRNA levels but increased heme oxygenase-1 (HO-1). Oral preadministration of AM and TH rescued mice from DSS-induced colitis by inhibiting inflammatory mediators via inactivated extracellular signal regulated kinase and repressed nuclear factor κB and signal transducer and activator of transcription 3, but the effect was weaker for sulfasalazine than that for the extracts. Anti-inflammatory activities occurred via the inhibition of macrophage and T lymphocyte infiltrations. Unlike sulfasalazine, which did not induce HO-1, TH extracts afforded significant HO-1 induction. Conclusions Because the AM or TH extracts were far superior in preventing DSS-induced colitis than sulfasalazine, AM or TH extracts can be considered natural agents that can prevent IBD relapse.

BACKGROUND Intramedullary nailing is the treatment of choice for atypical femoral fractures. However, several problems, such as iatrogenic fracture and medial gap opening, can occur during intramedullary nailing when atypical femoral fractures are associated with excessive anterolateral bowing. To overcome these problems, we have developed a new grading system for anterolateral femoral bowing and a new technique for intramedullary nailing. The core of this new technique is matching the anterior curvature of the femoral nail with the anterolateral bowing of the femur when the nail passes the apex of the curvature, by rotating the nail externally. METHODS From January 2005 through March 2016, 24 female patients (30 cases) who underwent a surgical procedure for atypical femoral fracture with anterolateral bowing at 2 institutes were evaluated. The postoperative outcomes (anterolateral bowing grade, anterior and lateral bowing angles, medial gap and posterior gap of the fracture site, iatrogenic fracture, and time to initial medial callus formation and osseous union) were compared between the new technique (18 cases) and the conventional technique (12 cases). RESULTS With regard to the reliability of the new grading system, the interobserver and intraobserver reliability of the new grading system demonstrated an almost perfect agreement (kappainter = 0.893, kappaintra = 0.883). For patients with complete fractures, the differences between the preoperative and postoperative anterior and lateral bowing angles were significantly less (p = 0.013 for both) in the new technique group. The medial and posterior gaps at the fracture site were also significantly less in the new technique group (p = 0.013 for the medial gaps and p = 0.022 for the posterior gaps). Iatrogenic fracture occurred only in the conventional technique group, affecting 2 cases. The time to initial medial callus formation was significantly shorter (p = 0.033) in the new technique group compared with the conventional technique group. CONCLUSIONS Our new grading system for anterolateral femoral bowing is convenient and reliable. Furthermore, the new intramedullary nailing technique with the current intramedullary nail system is appropriate for the repair of atypical femoral fractures with excessive anterolateral bowing. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background FOLFIRINOX has increased efficacy but also toxicity. Despite various modified FOLFIRINOX regimens, how much reduction is acceptable remains unclear. This study aimed to find the optimal relative dose intensity (RDI, %) of FOLFIRINOX that preserves tumour responses in patients with advanced pancreatic cancer (PC). Methods We reviewed 201 patients with PC treated with first-line FOLFIRINOX during 2012–2015. We established a modified Hryniuk model ( http://www.rdicalc.com ) and defined cumulative RDI (cRDI, %). The optimal cRDI thresholds for response rate (RR) and disease control rate (DCR) were assessed using receiver operating characteristic (ROC) analysis. Relationships between cRDI and haematologic toxicities (neutropenia and febrile neutropenia [FN]) were also analysed according to use of granulocyte colony-stimulating factor (G-CSF). Results Among 156 eligible patients, 133 (48 locally advanced PC and 85 metastatic PC) completed initial treatment plan prior to the first radiological evaluation (median 58 days; 71.8% cRDI). For optimal cRDI thresholds, ROC curves showed a 71.2% cRDI for RR (83.3% sensitivity, 64.7% specificity, and 0.746 area under the curve [AUC]) and a 55.3% cRDI for DCR (93.6% sensitivity, 62.5% specificity and 0.805 AUC). Among 96 patients who did not receive prophylactic G-CSF, cRDI ≥80.1% was a significant predictor for frequent FN (73.7% sensitivity, 72.7% specificity and 0.793 AUC). There was no correlation between cRDI and haematologic toxicities in patients receiving prophylactic G-CSF. Conclusion To preserve optimal RR and DCR in advanced PC, cRDI values for FOLFIRINOX >70% and >55%, respectively, are recommended. If cRDI is >80%, primary G-CSF prophylaxis is needed.

Background The purpose of this prospective, open-label, observational study was to assess the fracture preventing effect of Maxmarvil® tablets (alendronate 5 mg + calcitriol 0.5 µg) in patients with osteoporosis and to evaluate the change in bone mineral density (BMD) at the minimum 1-year follow-up. Methods In this multicenter observational study, 691 patients with osteoporosis (aged 50 years or older) were treated with alendronate 5 mg + calcitriol 0.5 µg/day during their normal course of care. Patients were assessed at baseline and at 6 and 12 months. Baseline characteristics (including age, gender, concomitant disease, and baseline fractures) were evaluated. Results From among the 848 participants, 149 individuals were lost to follow-up at the time of the study and 8 people had died. The 691 participants (54 men and 637 women) finished the follow-up study and completed the questionnaire. The mean age of the participants was 71.5 years (range, 50-92 years; mean age, 72.3 years for men and 71.4 years for women). Osteoporotic fracture occurred in 19 patients (2.7%). BMD of the lumbar spine and hip was improved by 5% and 1.5% at the latest follow-up. At the latest follow-up, 24 patients (3.5%) complained of drug-related complications such as dyspepsia, constipation, and nausea. Conclusions This prospective observational study demonstrated that alendronate 5 mg + calcitriol 0.5 µg/day had a preventive effect on osteoporotic fracture and it increased the BMD of the lumbar spine by 5% at the latest follow-up.

Background and Aim Palliative endoscopic or percutaneous biliary drainage is used for unresectable advanced hilar cancer (HC). The best option for drainage in Bismuth type III or IV HC has not been established. The aims of this study are to identify factors predictive of endoscopic stenting failure and evaluate the effectiveness of rescue percutaneous stenting in patients with advanced HC. Methods Data from 110 patients with inoperable advanced HC were retrospectively reviewed. All received bilateral self-expandable metallic stents. Patients were divided into three groups: I, successful initial endoscopic stenting; II, unsuccessful initial endoscopic stenting, followed by percutaneous stenting; and III, initial percutaneous stenting. We analyzed clinical results and radiologic tumor characteristics. Results Baseline characteristics and clinical outcomes of all groups were similar, except the hospital stay was longer in group III than group I. Technical success rate was higher in groups II and III (100%) than in group I (72.4%). The functional success rate, stent patency time, patient survival time, and complication rate were similar between groups. Endoscopic stenting failed because of guide-wire passage failure (n = 12) or stent passage failure (n = 7). The only factor significantly associated with endoscopic failure was a smaller left intrahepatic duct–common bile duct angle. Conclusions As clinical outcomes were generally similar between approaches, percutaneous stenting is recommended for patients with Bismuth type III or IV advanced HC. Acute left intrahepatic duct–common bile duct angulation predicts endoscopic stenting failure. If endoscopic stenting fails, immediate conversion to the percutaneous approach is a necessary and effective rescue method.

Background and Aims Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been proposed as an alternative management strategy for acute cholecystitis caused by malignant cystic duct obstruction in patients for whom surgery is not an option. This study aimed to compare the results of EUS-GBD with those of percutaneous transhepatic gallbladder drainage (PTGBD) for palliative management of malignant cystic duct obstruction with acute cholecystitis or symptomatic gallbladder hydrops. Methods Between November 2013 and November 2015, 14 patients with acute cholecystitis or symptomatic gallbladder hydrops as a result of malignant cystic duct obstruction underwent EUS-GBD with covered metal stents. Nineteen patients with acute cholecystitis as a result of malignant cystic duct obstruction who received PTGBD served as a control group. Patients' medical records were reviewed retrospectively. Results The technical and clinical success rates of EUS-GBD were 85.7% (12/14) and 91.7% (11/12) and of PTGBD were 100% (19/19) and 86.4% (17/19), respectively. The groups had similar adverse event rates (28.5% and 21.1%, respectively). The average duration of stent patency in patients with EUS-GBD was 130.3 ± 35.3 days, and no patient required an additional procedure before death. In 6 of 17 patients (35.3%) with clinically successful PTGBD, the catheter was not removed until the end stage of life. Conclusions EUS-GBD is a feasible, safe, and effective modality for the treatment of malignant cystic duct obstruction in patients who are not indicated for surgery. It enables improved long-term quality of life in patients with advanced-stage cancer.

Background: Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods: The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings: Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p

Objective: Delirium is an acute brain failure related to uncertain problems in neural connectivity, including aberrant functional interactions between remote cortical regions. This study aimed to elucidate the underlying neural mechanisms of delirium by clarifying the changes in resting-state functional connectivity induced by postoperative delirium using imaging data scanned before and after surgery. Method: Fifty-eight patients with a femoral neck fracture were preoperatively scanned using resting-state functional magnetic resonance imaging. Twenty-five patients developed postoperative delirium, and 14 of those had follow-up scans during delirium. Eighteen patients without delirium completed follow-up scans 5 or 6 days after surgery. We assessed group differences in voxel-based connectivity, in which the seeds were the posterior cingulate cortex, medial prefrontal cortex and 11 subcortical regions. Connections between the subcortical regions were also examined. Results: The results showed four major findings during delirium. Both the posterior cingulate cortex and medial prefrontal cortex were strongly connected to the dorsolateral prefrontal cortex. The posterior cingulate cortex had hyperconnectivity with the inferior parietal lobule, whereas the medial prefrontal cortex had hyperconnectivity with the frontopolar cortex and hypoconnectivity with the superior frontal gyrus. Connectivity of the striatum with the anterior cingulate cortex and insula was increased. Disconnections were found between the lower subcortical regions including the neurotransmitter origins and the striatum/thalamus in the upper level. Conclusions: Our findings suggest that cortical dysfunction during delirium is characterized by a diminution of the anticorrelation between the default mode network and task-positive regions, excessive internal connections in the posterior default mode network and a complex imbalance of internal connectivity in the anterior default mode network. These dysfunctions can be attributed to the loss of reciprocity between the default mode network and central executive network associated with defective function in the salience network, which might be closely linked to aberrant subcortical neurotransmission-related connectivity and striato-cortical connectivity.

The use of xanthan gum (XG) as a thickener increases solution viscosity, and therefore, the cost of subsequent processes such as fluid transportation and purification. Herein, we investigate the degradation of XG by urea, sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB). The results showed that CTAB degraded the XG more than SDS or urea. Interestingly, the degree of CTAB-induced degradation varied with the concentration regime. Thus, increasing CTAB concentration from 0.01 to 0.1 M decreased the complex viscosity (|η*|), whereas from 0.2 to 0.5 M the |η*| increased. For XG/SDS, the |η*| was unchanged with increasing SDS concentration from 0.01 to 0.1 M, whereas it decreased from 0.2 to 0.5 M. For XG/urea, the |η*| was stable in all concentrations. At the atomic-scale, computer simulations revealed that the degrading effect of CTAB was due to preferential interaction with the XG sidechain. These findings can enhance industrial applications of XG.

The aim of our study was to identify the risk factors for avascular necrosis of the femoral head (AVN) and fixation failure (FF) after screw osteosynthesis in patients with valgus angulated femoral neck fractures.We conducted a retrospective study of 308 patients (mean age, 72.5 years, range, 50-97 years), with a mean follow-up of 21.4 months (range, 12-64 months). The risk for failure in treatment (FIT) associated with patient- and fracture-related factors was evaluated by logistic regression analyses.FIT was identified in 32 cases (10.3%): 22 cases (7.1%) of AVN and 10 cases (3.2%) of FF. Initial valgus tilt15° (p=0.023), posterior tilt15° (p=0.012), and screw sliding distance (p=0.037) were significantly associated with FIT. FIT occurred in 7 patients (5.2%) with B1.2.1 fractures and 17 patients (48.6%) with B1.1.2 fractures (p0.001). The odds of FIT were 17-fold higher in patients with initial valgus and posterior tilts15° (B1.1.2) compared to patients with15° of tilt in both planes (B1.2.1).The severity of initial deformity predicts AVN and FF in patients with valgus angulated femoral neck fractures. Patients with an initial valgus and posterior tilt15° are reasonable candidates for primary arthroplasty due to high risk of FIT.

Ischemic limb diseases are induced by different obstructions of peripheral arteries. These obstructions result in insufficient nutrient and oxygen supplies to the extremities, thereby leading to severe tissue damage that is in turn related to severe morbidities and mortalities. Mesenchymal stem cells (MSCs) have been isolated from various sources. These cells are multipotent with respect to differentiation and are also characterized by migration, immune suppression, and secretion of paracrine factors. Mesenchymal stem cells have been proposed to have therapeutic potential for the treatment of ischemic limb diseases. In preclinical experiments, injection of single MSCs has been shown to increase angiogenesis and blood flow in ischemic hindlimb animal models; several molecular mechanisms of angiogenesis have also been elucidated. Furthermore, modified strategies have been developed for enhancing angiogenesis and the efficacy of MSCs. These strategies have demonstrated significant effects in pre-clinical studies. In clinical trials, MSCs have shown significant effects in the treatment of ischemic limb diseases. In this review, we focus on the therapeutic properties of human MSCs and the modified methods for enhancing angiogenesis in pre-clinical experiments. We also discuss the clinical applications of MSCs for treating limb ischemia.

An entrapment of the femoral artery by cerclage wiring is a rare complication after spiral diaphyseal femoral fractures. We report the case of an 82-year-old female treated by an antegrade intramedullary nailing and multiple cable augmentation, which was then complicated by injury to the femoral artery that resulted in ipsilateral leg necrosis and amputation. The entrapment was caused by direct belting by the cable and resulted in a total obstruction of the femoral artery.

Gelatin has been reported to induce generation of mesenchymal stem cells (MSCs) with enhanced potential of differentiation into neuronal lineage cells. However, the presence of various cell types besides MSCs in bone marrow has raised doubts about the effects of gelatin. In the following report, we determined whether gelatin can directly enhance neurogenic differentiation potential in MSCs without proliferation of neural progenitor cells (NPCs). MSCs comprised a high proportion of bone marrow-derived primary cells (BMPCs) and gelatin induced significant increases in MSC proliferation during primary culture, and the proportion of MSCs was maintained at more than 99% throughout the subculture. However, NPCs comprised a low percentage of BMPCs and a decrease in proliferation was detected despite gelatin treatment during the primary culture, and the proportion of subcultured NPCs gradually decreased. In a similar manner, MSCs exposed to gelatin during primary culture showed more enhanced neurogenic differentiation ability than those not exposed to gelatin. Together, these results demonstrate that gelatin directly enhances neurogenic differentiation in bone marrow-derived MSCs without stimulating NPC proliferation.

The treatment of a large segmental defect of over 6 cm in a long bone is a challenging procedure. Treatment options include cancellous bone graft (e.g., the Masquelet technique), vascularized fibular graft (VFG), and internal bone transport (IBT) with an external fixator. These methods may be performed with intramedullary (IM) nailing or plate fixation to enhance stability or to lessen the time of external fixation. Each method has its own advantages and limitations. This study aimed to describe the advantages of additional plate augmentation and autologous bone grafting after IM nail implantation. Three patients with large segmental femoral bone defects were treated with IM nail implantation; then, one- or two-stage autologous iliac bone grafting with additional plate augmentation was performed. All patients achieved bony union without metal failure. We describe a technique involving additional plate augmentation and autologous iliac bone grafting for treating large femoral defects after restoring the length of the femur using an IM nail implantation and an external fixator.

Structural compromise of the tumor suppressor gene, phosphatase and tensin homolog (PTEN), occurs in 10% of melanoma specimens, and loss of PTEN expression through DNA methylation of the PTEN promoter region has also been reported in a number of other malignancies. However, the role of PTEN promoter methylation in melanoma is not well understood. We thus sought to elucidate the prevalence of PTEN promoter methylation in melanoma specimens, its relationship to clinical features, and its impact on the outcome of patients with melanoma. PTEN promoter methylation data were acquired from an archived primary Korean melanoma cohort (KMC) of 158 patients and, for validation, 234 patients from The Cancer Genome Atlas melanoma (TCGA-MEL) cohort. Hierarchical clustering was performed to identify PTEN "high methylated" and "low methylated" samples. Subsequently, differences in clinical features and outcomes based on PTEN promoter methylation status were then analyzed using SPSS and R. In the KMC, all tumors were acquired from primary tumors and 65.7% (n = 105) were acral or mucosal by site, whereas in the TCGA-MEL cohort, 90.5% of the tumors were from regional lymph node and distant metastatic lesions. Overall, 17.7% and 45.7% of the specimens harbored BRAF mutations in the KMC and TCGA-MEL cohort, respectively. Neuroblastoma RAS viral oncogene homolog was mutated in 12.2% and 26.9% of the tumors in the KMC and TCGA-MEL cohort, respectively. In the KMC, 31 cases (19.6%) were included in the high methylated group versus 142 cases (60.7%) in the TCGA-MEL cohort (P0.001). Multivariate Cox-regression analysis revealed promoter methylation of PTEN to be an independent negative prognostic factor for survival in both the KMC (hazard ratio 3.76, 95% confidence interval = 1.24-11.12, P = 0.017) and TCGA-MEL cohort (HR 1.88, 95% confidence interval = 1.13-3.12, P = 0.015). Our results indicate that PTEN promoter methylation is an independent predictor for impaired survival in patients with melanoma.

Sinonasal mucosal melanoma (SMM) is an aggressive and rare type of melanoma. Although the classic RAS-RAF-MEK pathway is thought to be the main pathway involved in melanoma pathogenesis, genetic alterations in the phosphatidylinositol 3-kinase-AKT pathway, including PTEN-regulated signaling, are also thought to contribute. So far, data regarding altered PTEN expression and epigenetic mechanism of PTEN silencing in development of SMM is extremely limited. Herein we report on a case of SMM with liver and bone metastases with an epigenetic alteration of PTEN. Results of mutation analysis for BRAF, NRAS, HRAS, KRAS, PIK3CA, c-Kit, and PTEN were negative; however, methylation of PTEN CpG islands was observed. Our case not only supports PTEN as a major tumor suppressor involved in melanoma tumorigenesis, but also a potential epigenetic mechanism of PTEN silencing in development of SMM.

// Joo Hoon Kim 1, * , Jae Seok Lee 2, * , Eo Jin Kim 2 , Kyu Hyun Park 3 , Ki Hyang Kim 4 , Seong Yoon Yi 5 , Han Seong Kim 6 , Yong Jin Cho 7 , Kyoo-Ho Shin 7 , Joong Bae Ahn 1 , Hyuk Hu 8 , Kyung Sik Kim 8 , Young Deuk Choi 9 , Sunghoon Kim 10 , Young Han Lee 11 , Jin-Suck Suh 11 , Sung Hoon Noh 8 , Sun Young Rha 1 , Hyo Song Kim 1 1 Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea 2 Department of Pathology, Dongguk University College of Medicine, Dongguk University Ilsan Hospital, Goyang, Korea 3 Cancer Metastasis Research Center, Song Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Korea 4 Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea 5 Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Ilsan, Korea 6 Department of Pathology, Ilsan Paik Hospital, Inje University College of Medicine, Ilsan, Korea 7 Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, Korea 8 Department of Surgery, Yonsei University College of Medicine, Seoul, Korea 9 Department of Urology, Yonsei University College of Medicine, Seoul, Korea 10 Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea 11 Department of Radiology, Yonsei University College of Medicine, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Sun Young Rha, e-mail: rha7655@yuhs.ac Hyo Song Kim, e-mail: hyosong77@yuhs.ac Keywords: liposarcoma, PIK3CA, amplification, mutation Received: January 05, 2016 Accepted: March 02, 2016 Published: March 21, 2016 ABSTRACT Background: We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutations/amplifications in curative resected liposarcoma. Patients and methods: A total of 125 liposarcoma tissue samples were collected over a 12-year period. PIK3CA mutations and gene copy number amplifications were analyzed by pyrosequencing and fluorescence in situ hybridization (FISH). Results: Nine of the 105 liposarcomas (8.6%) had activating PIK3CA mutation. PIK3CA mutations were more frequent in myxoid/round cell and pleomorphic tumors compared with well-differentiated/dedifferentiated tumors (13.3% vs. 2.2%, P=0.043). In FISH PIK3CA analysis, copy number gain was detected in 14 of the 101 tumors (13.9%): 11 (10.9%) tumors had increased gene copy number (polysomy) and 3 (3.0%) exhibited gene amplification. In survival analysis, patients with PIK3CA copy number gain had a worse prognosis compared to patients without PIK3CA amplification (median disease-free survival [DFS] 22.2 vs. 107.6 months p=0.005). By multivariate analysis, PIK3CA copy number gain was an independent prognostic factor for worse DFS (P=0.027; hazard ratio, 2.400; 95% confidence interval 1.105 to 5.213). PIK3CA mutation was not associated with DFS and overall survival. Conclusions: We demonstrated PIK3CA mutation and amplification in liposarcoma. PIK3CA copy number gain was an independent poor prognostic factor for DFS. Further studies are needed to evaluate the potential diagnostic and therapeutic role of PIK3CA mutations and amplifications in liposarcoma.

PURPOSE Hypermethylation of the CpG island of p16(INK4a) occurs in a significant proportion of colorectal cancer (CRC). We aimed to investigate its predictive role in CRC patients treated with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), and cetuximab. MATERIALS AND METHODS Pyrosequencing was used to identify KRAS mutation and hypermethylation of 6 CpG island loci (p16, p14, MINT1, MINT2, MINT31, and hMLH1) in DNA extracted from formalin-fixed paraffin-embedded specimens. Logistic regression and Cox regression were performed for analysis of the relation between methylation status of CpG island methylator phenotype (CIMP) markers including p16 and clinical outcome. RESULTS Hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) and showed significant association with KRAS mutation (Fisher exact, p=0.01) and CIMP positivity (Fisher exact, p=0.002). Patients with p16-unmethylated tumors had significantly longer time to progression (TTP; median, 9.0 months vs. 3.5 months; log-rank, p=0.001) and overall survival (median, 44.9 months vs. 16.4 months; log-rank, p=0.008) than those with p16-methylated tumors. Patients with both KRAS and p16 aberrancy (n=6) had markedly shortened TTP (median, 2.8 months) compared to those with either KRAS or p16 aberrancy (n=11; median, 8.6 months; p=0.021) or those with neither (n=32; median, 9.0 months; p < 0.0001). In multivariate analysis, KRAS mutation and p16 methylation showed independent association with shorter TTP (KRAS mutation: hazard ratio [HR], 3.21; p=0.017; p16 methylation: HR, 2.97; p=0.027). CONCLUSION Hypermethylation of p16 was predictive of clinical outcome in metastatic CRC patients treated with cetuximab and FOLFIRI, irrespective of KRAS mutation.

Background/Aims: For the suspected choledocholithiasis, the American Society for Gastrointestinal Endoscopy has proposed guidelines to assign risk based on clinical predictors. The study aimed to assess the usefulness of clinical predictors of choledocholithiasis set forth by the guidelines in patients with intermediate risk of choledocholithiasis. Methods: In 2014, 109 patients with intermediate risk of choledocholithiasis underwent endoscopic ultrasound. Their medical records were retrospectively reviewed. The gold standard for choledocholithiasis was endoscopic retrograde cholangiopancreatography or clinical follow-up. Results: Based on endoscopic ultrasound findings, choledocholithiasis was suspected in 18 patients, and it was removed in 17 patients. Choledocholithiasis was absent in the remaining 91 who did not show any signs from endoscopic ultrasound. Among the 2 strong (common bile duct (CBD) diameter >6 mm and bilirubin 1.8-4 mg/dl) and 3 moderate (abnormal liver biochemical test other than bilirubin, age >55 years and gallstone pancreatitis) clinical predictors, 28.8% of patients with one of the strong predictors had choledocholithiasis; however, only 3.5% of patients with any one of the moderate predictors had choledocholithiasis. As a result, only strong clinical predictors showed predictability: increased bilirubin level (OR 3.23; 90% CI 0.85-12.28) and dilated CBD diameter (OR 5.83; 90% CI 1.93-17.57). Conclusion: Only strong clinical predictors of choledocholithiasis showed predictability for patients with intermediate risk of choledocholithiasis.

Peritoneal carcinomatosis accompanied by malignant ascites is a major cause of death of advanced gastric cancer (GC). To comprehensively characterize the underlying genomic events involved in GC peritoneal carcinomatosis, we analyzed whole-exome sequences of normal gastric tissues, primary tumors, and malignant ascites from eight GC patients. We identified a unique mutational signature biased toward C-to-A substitutions in malignant ascites. In contrast, the patients who received treatment of adjuvant chemotherapy showed a high rate of C-to-T substitutions along with hypermutation in malignant ascites. Comparative analysis revealed several candidate mutations for GC peritoneal carcinomatosis: recurrent mutations in COL4A6, INTS2, and PTPN13; mutations in druggable genes including TEP1, PRKCD, BRAF, ERBB4, PIK3CA, HDAC9, FYN, FASN, BIRC2, FLT3, ROCK1, CD22, and PIK3C2B; and mutations in metastasis-associated genes including TNFSF12, L1CAM, DIAPH3, ROCK1, TGFBR1, MYO9B, NR4A1, and RHOA. Notably, gene ontology analysis revealed the significant enrichment of mutations in the Rho-ROCK signaling pathway-associated biological processes in malignant ascites. At least four of the eight patients acquired somatic mutations in the Rho-ROCK pathway components, suggesting the possible relevance of this pathway to GC peritoneal carcinomatosis. These results provide a genome-wide molecular understanding of GC peritoneal carcinomatosis and its clinical implications, thereby facilitating the development of effective therapeutics.