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1. Moulting is a natural physiological process in birds when they shed their old feathers and replace them with new ones, and it is followed by reproductive quiescence resulting in reduced egg production. Different birds undergo moulting at different points in their life. Some birds have seasonal moulting while some moult at the end of their breeding cycle. This review will mainly focus on moulting practices associated with commercial layer birds because, in all other bird types, this is not managed.2. Commercial farms commonly analyse the cost-benefit ratio to decide the time and method to adopt for moulting. Commercial layer farms adopt different practices to force birds out of moult and restart the production cycle. Animal welfare groups consider this as stressful and against animal welfare, raising questions about the ethics of this practice.3. Many studies have been conducted using complete or partial feed withdrawal and non-feed withdrawal programs to measure their effectiveness in maintaining animal welfare, economy, and post-moult performance in mind.4. Animal welfare should not be compromised during moulting. The United States Egg Producers and other such groups from the United Kingdom and Europe have decided to sell eggs produced only through a non-feed withdrawal moulting programs.

Background Women with cosmetic breast implants have significantly lower rates of subsequent breast cancer than the general population (relative risk, 0.63; 95 percent CI, 0.56 to 0.71). The authors hypothesize that breast implant-induced local inflammation stimulates immunosurveillance recognition of breast tumor antigen. Methods Sera were collected from two cohorts of healthy women: women with long-term breast implants (i.e., breast implants for >6 months) and breast implant-naive women. Antibody responses to breast tumor antigens were tested by enzyme-linked immunosorbent assay and compared between cohorts by unpaired t test. Of the implant-naive cohort, nine women underwent breast augmentation, and antibody responses before and after implant placement were compared by paired t test. Results Sera were collected from 104 women: 36 (34.6 percent) long-term breast implants and 68 (65.4 percent) implant-naive women. Women with long-term breast implants had higher antibody responses than implant-naive women to mammaglobin-A (optical density at 450 nm, 0.33 versus 0.22; p = 0.003) and mucin-1 (optical density at 450 nm, 0.42 versus 0.34; p = 0.02). There was no difference in antibody responses to breast cancer susceptibility gene 2, carcinoembryonic antigen, human epidermal growth factor receptor-2, or tetanus. Nine women with longitudinal samples preoperatively and 1 month postoperatively demonstrated significantly elevated antibody responses following implant placement to mammaglobin-A (mean difference, 0.13; p = 0.0002) and mucin-1 (mean difference 0.08; p = 0.02). There was no difference in postimplant responses to other breast tumor antigens, or tetanus. Conclusions Women with long-term breast implants have higher antibody recognition of mammaglobin-A and mucin-1. This study provides the first evidence of implant-related immune responses to breast cancer antigens. Clinical question/level of evidence Therapeutic, V.

A major rate-limiting step in developing more effective immunotherapies for GBM is our inadequate understanding of the cellular complexity and the molecular heterogeneity of immune infiltrates in gliomas. Here, we report an integrated analysis of 201,986 human glioma, immune, and other stromal cells at the single cell level. In doing so, we discover extensive spatial and molecular heterogeneity in immune infiltrates. We identify molecular signatures for nine distinct myeloid cell subtypes, of which five are independent prognostic indicators of glioma patient survival. Furthermore, we identify S100A4 as a regulator of immune suppressive T and myeloid cells in GBM and demonstrate that deleting S100a4 in non-cancer cells is sufficient to reprogram the immune landscape and significantly improve survival. This study provides insights into spatial, molecular, and functional heterogeneity of glioma and glioma-associated immune cells and demonstrates the utility of this dataset for discovering therapeutic targets for this poorly immunogenic cancer.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma that has remained a challenge for oncologic and reconstructive surgeons due to a high rate of local recurrence. The objective of this study is to investigate the oncologic and reconstructive benefits of employing a multidisciplinary two-step approach to the treatment of DFSP. A retrospective review was conducted using a prospectively collected database of all patients who underwent resection and reconstruction of large DFSPs by a multidisciplinary team, including a Mohs micrographic surgeon, surgical oncologist, dermatopathologist, and plastic and reconstructive surgeon, at one academic institution from 1998-2018. Each patient underwent Mohs micrographic surgery for peripheral margin clearance (Step 1) followed by wide local excision (WLE) of the deep margin by surgical oncology and immediate reconstruction by plastic surgery (Step 2). 57 patients met inclusion criteria. Average defect size after WLE (Step 2): 87.3 cm

Importance Although various treatments have been found in clinical trials to be effective in treating actinic keratosis (AK), researchers often report different outcomes. Heterogeneous outcome reporting precludes the comparison of results across studies and impedes the synthesis of treatment effectiveness in systematic reviews. Objective To establish an international core outcome set for all clinical studies on AK treatment using systematic literature review and a Delphi consensus process. Evidence Review Survey study with a formal consensus process. The keywordsactinic keratosisandtreatmentwere searched in PubMed, Embase, CINAHL, and the Cochrane Library to identify English-language studies investigating AK treatments published between January 1, 1980, and July 13, 2015. Physician and patient stakeholders were nominated to participate in Delphi surveys by the Measurement of Priority Outcome Variables in Dermatologic Surgery Steering Committee members. All participants from the first round were invited to participate in the second round. Outcomes reported in randomized controlled clinical trials on AK treatment were rated via web-based e-Delphi consensus surveys. Stakeholders were asked to assess the relative importance of each outcome in 2 Delphi survey rounds. Outcomes were provisionally included, pending the final consensus conference, if at least 70% of patient or physician stakeholders rated the outcome as critically important in 1 or both Delphi rounds and the outcome received a mean score of 7.5 from either stakeholder group. Data analysis was performed from November 5, 2018, to February 27, 2019. Findings A total of 516 outcomes were identified by reviewing the literature and surveying key stakeholder groups. After deduplication and combination of similar outcomes, 137 of the 516 outcomes were included in the Delphi surveys. Twenty-one physicians and 12 patients participated in round 1 of the eDelphi survey, with 17 physicians (81%) retained and 12 patients (100%) retained in round 2. Of the 137 candidate outcomes, 9 met a priori Delphi consensus criteria, and 6 were included in the final outcomes set after a consensus meeting: complete clearance of AKs, percentage of AKs cleared, severity of adverse events, patient perspective on effectiveness, patient-reported future treatment preference, and recurrence rate. It was recommended that treatment response be assessed at 2 to 4 months and recurrence at 6 to 12 months, with the AK rate of progression to cutaneous squamous cell carcinoma reported whenever long-term follow-up was possible. Conclusions and Relevance Consensus was reached regarding a core outcome set for AK trials. Further research may help determine the specific outcome measures used to assess each of these outcomes.

Objectives No randomized controlled trials have evaluated the comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. Methods A prospective observational cohort study including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (≥15 years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive antibiotics were included. The rates of treatment failure (premature discontinuation of antibiotics because of adverse effects, switching of antibiotics because of clinical failure, all-cause mortality within 1 month, or recurrence) were compared between the cefazolin and nafcillin groups. Propensity score matching analyses were performed to balance the factors influencing the selection of antibiotics. Results Among the 242 included cases, the bones and joints (36.8%) were the most common sites of infection and 60.7% of the patients had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause mortality within 1 month was 6.2% (15/242). After propensity score matching, the treatment failure rate of cefazolin was lower than that of nafcillin (30.4% (24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation caused by adverse events. When the data were limited to patients with sepsis, the treatment failure rates of both groups were not significantly different. Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect (CIE) that had significant impact on the failure rate and mortality of the cefazolin group. Conclusions Cefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE.

While haemodynamic variability interferes with the assumption of constant flow underlying thermodilution cardiac output calculation, variability in (peripheral) arterial vascular physiology may affect pulse contour cardiac output methods. We compared non-invasive finger arterial pressure-derived continuous cardiac output measurements (Nexfin® ) with cardiac output measured using thermodilution during cardiothoracic surgery and determined the impact of cardiovascular variability on either method. We compared cardiac output derived from non-invasive finger arterial pressure with cardiac output measured by thermodilution at four grades (A-D) of cardiovascular variability. We defined Grade A data as heart rate and mean arterial pressure variability < 5% and the absence of arrhythmias (implying stable flow) and Physiocal® interval (as measure of variability in finger arterial physiology) > 30 beats. Grade B included all levels of heart rate/mean arterial pressure variability and arrhythmias (Physiocal < 30 excluded). Grade C included all Physiocal intervals (heart rate/mean arterial pressure variability > 5% and arrhythmias excluded). Grade D included all data. Comparison results were quantified as percentage errors. We analysed measurements in 27 patients undergoing coronary artery bypass surgery. Before extracorporeal circulation, the percentage error was 23% (n = 14 patients) in grade A, 28% (n = 20) in grade B, 32% (n = 22) in grade C and 37% (n = 26) in grade D, with a significant increase in variance (p = 0.035). Bias did not differ between grades. After extracorporeal circulation (n = 27), percentage errors became larger, but were not different between grades. Variability during cardiothoracic surgery affected the comparison between thermodilution and non-invasive finger arterial pressure-derived cardiac output. When the main sources of variability were included, percentage errors were large. Future cardiac output methodology comparison studies should report haemodynamic variability.

OBJECTIVE: To examine the relationship between high-sensitivity C-reactive protein (hs-CRP) levels and lung function in a community-based cohort of South Korea.DESIGN: The Ansung-Ansan cohort database (an ongoing prospective study of a community-based population) was used in the analysis. We defined airway obstruction as the ratio between forced expiratory volume in 1 sec:forced vital capacity ratio (FEV1:FVC) of RESULTS: A total of 5528 individuals were eligible for the study. The average age was 55.1 years, and 47.8% were males. The prevalence of airway obstruction was 9.0%, and the mean hs-CRP level was 1.51 mg/dl. Serum hs-CRP levels increased with the severity of airway obstruction, and the latter worsened with an increase in the hs-CRP level. In multivariate analysis, as the hs-CRP level increased, FEV1 and FVC decreased. A higher FEV1:FVC ratio was associated with lower hs-CRP levels in males.CONCLUSION: Higher hs-CRP levels were associated with decreased FEV1 and FVC in a general population of Korea. The FEV1:FVC ratio decreased with an increase in the hs-CRP level in males.

Objective To evaluate the acceptance of, adherence to, and outcomes of latent tuberculous infection (LTBI) treatment among health care workers (HCWs). Design This was a retrospective study in a tertiary hospital in Korea. From May to August 2017, 2190 HCWs simultaneously underwent a tuberculin skin test (TST) and interferon-gamma release assay (IGRA). LTBI was diagnosed if the TST induration was 10 mm or IGRA results were positive. Results Of 2190 HCWs tested, 1006 (45.9%) were diagnosed with LTBI. Of these, 655 (65.1%) HCWs visited out-patient clinics, 234 (35.7%) of whom were advised treatment by physicians. Among these, 120 (51.3%) accepted the physicians' recommendations. In general, HCWs who were older, male and smoked were less likely to visit out-patient clinics. Sixty (50%) HCWs received 3 months of isoniazid plus rifampicin (3HR) and 57 (47.5%) HCWs received 4 months of rifampicin (4R). The proportion of HCWs with 2 side effects (3HR 20% vs. 4R 7.0%, P = 0.041) and drug stoppage rate (3HR 20% vs. 4R 5.3%, P = 0.017) were higher in the 3HR group than in the 4R group. Of the 120 HCWs, 78 (65%) completed LTBI treatment. Conclusion Overall, the acceptance and completion rate for LTBI treatment was not adequate. For effective LTBI management in HCWs, further programmatic strategies are needed.

Adnexal torsion occurs when the ovary and fallopian tube twist on the axis created between the infundibulopelvic ligament and the utero-ovarian ligament. The symptoms are mostly unspecific and diagnosis is therefore not simple. Early diagnosis is essential to preserve organ function and fertility. The increased use of assisted reproductive technologies has led to an increase in the risk of adnexal torsion, particularly in pregnant women or women with ovarian hyperstimulation syndrome (OHSS). A gestational age eight-week pregnant woman who received in vitro fertilization (IVF) came to the clinic and was suspected of adnexal torsion. The patient underwent an operation and the biopsy histologically confirmed ischemia. Here the authors report a case with comparison to other studies, the early diagnosis, and early operation that could save adnexa.

Aims To determine quality of life (QoL) outcomes after palliation of pain from bone metastases using magnetic resonance-guided high intensity focused ultrasound (MR-guided HIFU), measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL and the QLQ-BM22 questionnaires. Materials and methods Twenty patients undergoing MR-guided HIFU in an international multicentre trial self-completed the QLQ-C15-PAL and QLQ-BM22 questionnaires before and on days 7, 14, 30, 60 and 90 post-treatment. Descriptive statistics were used to represent changes in symptom and functional scales over time and to determine their clinical significance. QoL changes were compared in pain responders and non-responders (who were classified according to change in worst pain score and analgesic intake, between baseline and day 30). Results Eighteen patients had analysable QoL data. Clinically significant improvements were seen in the QoL scales of physical functioning, fatigue, appetite loss, nausea and vomiting, constipation and pain in the 53% of patients who were classified as responders at day 30. No significant changes were seen in the 47% of patients who were non-responders at this time point. Conclusion Local treatment of pain from bone metastases with MR-guided HIFU, even in the presence of disseminated malignancy, has a substantial positive effect on physical functioning, and improves other symptomatic QoL measures. This indicated a greater response to treatment over and above pain control alone. MR-guided HIFU is non-invasive and should be considered for patients with localised metastatic bone pain and poor QoL., Highlights • High intensity focused ultrasound (HIFU) palliates localised metastatic bone pain. • Quality of life (QoL) after HIFU improved in pain responders more than in non-responders. • Systemic QoL improved after HIFU to a single painful site, even in those with disseminated disease. • Physical functioning was improved after HIFU, even in patients with end-stage disease.

We compared the accuracy for localizing arterial occlusion sites between delayed-phase computed tomography angiography (CTA) and arterial-phase CTA in acute stroke patients with large vessel occlusion. Institutional Review Board approval was obtained, and informed consent was waived. For patients treated with intra-arterial thrombolysis within a 6 hour window between January 2009 and November 2011, we retrospectively assessed the arterial occlusion sites of pre-treatment, delayed-phase and arterial-phase CTA and compared these with digital subtraction angiography (DSA) findings. The positive predictive value for detection of vessel occlusion for both CTA methods was derived using DSA as a reference standard. The outcomes were compared using the McNemar test. Inter-observer disagreement within each modality was assessed using the Kendall W test. Among 73 patients treated with intra-arterial thrombolysis, 24 (32.9%) underwent both arterial-phase and delayed-phase CTA, and 66 (90.4%) underwent arterial-phase CTA only. For 24 patients undergoing both arterial-phase and delayed-phase CTA, the delayed-phase CTA detected concordant occlusion sites with DSA in 21 patients, yielding a positive predictive value of 87.5%, whereas the arterial-phase CTA detected this in 14 patients, for a positive predictive value of 58.3% (p=0.013). When discordant with DSA, arterial-phase or delayed-phase CTA indicated occlusions in more proximal sites than DSA. Delayed-phase CTA more precisely localized the occlusion site than arterial-phase CTA in acute stroke patients with large vessel occlusion. Thus, delayed-phase CTA findings could guide neurointerventionists in selecting intra-arterial thrombolysis modalities.

Summary Background Androgenetic alopecia (AGA) is the most common type of hair loss, and is characterized by the transformation of terminal scalp hair into vellus hair. The epidemiology of AGA is not fully understood. A strong genetic basis has long been identified, although little is known of its nongenetic causes. Aim To evaluate the association of AGA with a number of environmental factors, including smoking, drinking and sleeping habit. Methods In total, 3114 Korean individuals with AGA who attended any one of 17 dermatology clinics in 6 cities in South Korea between March 2011 and February 2012 were enrolled in the study. Epidemiologic a data were collected using a standard questionnaire. Results No association was seen between eating or sleeping habits and severity of hair loss. However, drinking and smoking were associated with the severity of AGA in male patients. We also found that patients of both genders with a family history had more advanced types of hair loss, and the age of onset of AGA in male patients with a family history was earlier than that in male patients without a family history. Conclusions Although the evidence for an environmental influence on AGA remains very weak, we did find an association between hair loss severity and certain environmental factors, such as smoking and drinking. Family history with more severe hair loss and an earlier age of onset.

To evaluate the long-term clinical benefit and effectiveness of switching to once-daily quetiapine extended release (XR) from an oral antipsychotic in patients with schizophrenia. Reasons for switching included insufficient efficacy, tolerability, and/or non-acceptability. The primary endpoint was the percentage of patients achieving an improvement in Clinical Global Impression - Clinical Benefit (CGI-CB) scale scores.A 24-week, international, multicentre, open-label, prospective study ( www.clinicaltrials.gov : NCT00640601). After a 7-14 day enrolment period (depending whether prior antipsychotic mono- or combination therapy), all patients received quetiapine XR 300 mg once daily (day 1), 600 mg/day (day 2), 600-800 mg/day (day 3) and 400-800 mg/day thereafter, with down-titration and discontinuation of prior antipsychotic by day 4.A total of 62% of patients completed the study and 56.9% (LOCF, ITT) achieved a significant improvement in CGI-CB (95% CI [0.51, 0.63]; p = 0.02). Switches due to insufficient efficacy showed a significant improvement (60%, 95% CI [0.51, 0.68]; p = 0.02), compared to 54.4% ([0.44, 0.64]; p = 0.38) and 52.4% ([0.36, 0.68]; p = 0.76) of switches due to insufficient tolerability and non-acceptability respectively (both p = ns). Patients previously on olanzapine and quetiapine IR showed a significant improvement in CGI-CB (62.6% [p = 0.02] and 61.2% [p = 0.04], respectively). Somnolence (18.0%) and dizziness (14.6%) were the main adverse events. Anticholinergic use decreased from 7.1 to 2.7%. Overall mean weight gain was 0.4 kg; 12.9% of patients experienced a weight gain of ≥7% and 15% experienced a clinically relevant shift in triglycerides from baseline.A majority of patients switched from other antipsychotics to quetiapine XR experienced clinical benefit. This was supported by all other efficacy outcomes regardless of the reason for switching. Safety data confirmed quetiapine XR was safe and well tolerated. The open-label design and lack of a placebo group represent limitations.

Aim This study was designed to assess the efficacy and safety of the dipeptidyl peptidase IV inhibitor gemigliptin (LC15-0444) 50 mg versus placebo in patients with type 2 diabetes. Methods We conducted a 24-week, randomized, double-blind, placebo-controlled phase III trial in 182 patients (74 from Korea and 108 from India) with type 2 diabetes. After an initial 2 weeks of a diet and exercise programme followed by 2 weeks of a single-blind placebo run-in period, eligible patients were randomized to gemigliptin 50 mg or placebo, receiving the assigned treatment for 24 weeks. HbA1c and fasting plasma glucose (FPG) were measured periodically, and oral glucose tolerance test was performed at baseline and weeks 12 and 24. Results At week 24, gemigliptin treatment led to significant reductions in HbA1c measurements compared to placebo (adjust mean after subtracting the placebo effect size: −0.71%, 95% confidence interval: −1.04 to −0.37%). A significantly greater proportion of patients achieved an HbA1c

Background Non-invasive body sculpting procedures are becoming increasingly popular. High-intensity focused ultrasound (HIFU) treatment is a non-surgical fat reduction procedure that permanently destroys unwanted abdominal fat. Despite its increasing popularity, evaluation methods for the procedure have not yet been fully developed. Aims The objective of this study was to develop evaluation methods for HIFU for non-surgical, permanent fat reduction in the anterior abdomen using a porcine model. Methods The abdomens of female pigs (Sus scrofa, n = 7) were treated with a HIFU device (SCIZER™, Classys Inc, Seoul, Korea). We examined treatment effects using photography, ultrasound, gross and microscopic pathology, and serum lipid and liver function level analysis, carbon tracer test, and histological examination in order to determine the mechanism of action, efficacy, and safety of the procedure. Results HIFU treatment effectively reduced abdominal fat in a porcine model; it accurately treated the target subcutaneous fat layer and the subcutaneous fat was reduced effectively via ultrasonic measurement after HIFU treatment. On histological staining (H&E, toluidine blue, oil red O and immunohistochemistry), we found that subcutaneous fat reduction occurred effectively via accurate treatment of the targeted subcutaneous fat layer. On hematological assay, there were changes within normal range, and values remained stable after 48 h. Via carbon tracer test, the migration of activated macrophages was identified within the axillary lymph node (LN). PPAR-delta, a protein defined by immunohistochemistry staining, was overexpressed in the early stage on days 1 and 7, but a gradual decreasing pattern was confirmed. Conclusion We successfully used a HIFU device for body contouring and fat reduction in a pre-clinical study. These results provide that the essential clues toward the effective evaluation, guiding selection of the appropriate diagnostic investigations.

SUMMARYThe incidence and severity ofClostridium difficileinfections (CDI) have increased in Western countries. However, there are limited data regarding the epidemiology of CDI in Eastern countries. This nationwide study was conducted in 17 hospitals to determine temporal trends in CDI incidence (from 2004 to 2008) in South Korea. The total incidence of CDI in Korea was 1·7 cases/1000 adult admissions in 2004, and 2·7/1000 cases in 2008 (P = 0·028). When analysing the clinical features of 1367 CDI patients diagnosed in 2008, oral metronidazole was effective as a first-line treatment for CDI (61·9%). Relapse rate was 8·9% and complicated CDI was only observed in 3·6%. The incidence of CDI increased significantly in Korea from 2004 to 2008. Although the clinical features were milder than in Western countries, the increasing burden of CDI needs ongoing surveillance systems.

Objective To examine pre-transplant risk factors for the development of post-kidney transplant tuberculosis (TB) in an intermediate TB burden country, as this is important for early detection and prophylaxis to prevent post-transplant TB. Design A retrospective, longitudinal cohort study of 1097 kidney transplant patients was performed at the Severance Hospital, Seoul, South Korea, between January 2000 and March 2010. The standardised incidence ratio (SIR) of post-transplant TB compared to the general population was calculated and pre-transplant risk factors were analysed. Results Among the 1097 kidney transplant patients, 2.1% (23/1097) developed post-transplant TB, with an incidence of 445.2 cases per 100,000 patients per year. The SIR of TB in kidney transplant patients compared with the general population was 4.26 (95%CI 2.6-6.45). A positive tuberculin skin test (TST; RR 3.54, 95%CI 1.13-11.11, P = 0.03) and previously healed TB on chest radiograph (CXR; RR 8.71, 95%CI 1.00-75.84, P = 0.05) were significant pre-transplant risk factors for post-transplant TB on multivariate analysis. Conclusion The incidence of TB in kidney transplant patients was higher than in the general population. Positive TST results and previously healed TB lesions visible on pre-transplant CXR were significant pre-transplant risk factors for post-kidney transplant TB.

We investigated soluble human leukocyte antigen-G (sHLA-G) expression according to the phases of hepatitis B virus (HBV) infections and hepatocellular carcinoma (HCC). A total of 267 sera from anti-HBs positive healthy individuals (n = 50), chronic HBV carriers (n = 45), as well as patients with active hepatitis B (n = 46), liver cirrhosis (LC, n = 46) and early stage HCC (n = 80) were collected and assayed for sHLA-G. Relationships between sHLA-G levels and clinicopathologic parameters including HCC stages, differentiation grades, and levels of aminotransferases, HBV DNA and alpha-fetoprotein (AFP) were assessed. Concentrations of sHLA-G were higher in the active hepatitis B and HCC groups (median sHLA-G 53.7 and 178.8 U/ml, respectively) in comparison to other groups (P < 0.05), and there were no significant differences among sHLA-G levels of the anti-HBs positive, chronic HBV carrier and LC groups. Serum sHLA-G concentrations were not shown to be associated with clinicopathologic indices including the levels of aminotransferases, AFP, anti-HBs titer, HBV DNA, as well as HCC stages, numbers of tumor nodules, pathologic grades and presence of vessel invasion. The receiver-operating characteristic area under the curve (AUC) value of sHLA-G for differentiating HCC from LC was 0.98, which was greater than that of AFP (0.78) (P < 0.0001), and sensitivity and specificity of sHLA-G were, respectively, 90.0% and 95.7% for HCC when applying a cutoff level of 97.3 U/ml. Serum sHLA-G levels could be used as a diagnostic marker for HCC. Although sHLA-G levels did not reflect the severity of HBV infections and HCC, they were related with phases of the disease.

Increased adiposity, shorter stature, shorter leg length and carotid intima-media thickening are associated with cardiovascular (CV) disease. This study aimed to evaluate the sex-specific phenotypic and genetic associations between adiposity and anthropometric measures and carotid intima-media thickness (IMT).We measured IMT at common carotid artery (CCA-IMT), carotid bifurcation and internal carotid artery (ICA-IMT) using B-mode ultrasound, and adiposity and anthropometric measures, including body mass index (BMI), height, leg length, waist circumference (WC), waist-to-hip ratio and percentage of body fat; we also assessed conventional CV risk factors among 706 Korean adults from the Healthy Twin Study. The associations were analyzed using quantitative genetic and linear mixed analyses.In linear mixed analyses, BMI and WC had independent associations with the IMT at CCA-IMT and ICA-IMT and CCA-IMT, respectively, after adjusting for age and conventional CV risk factors in men. By comparison, in women, adiposity and anthropometric measures were associated with carotid IMT only before adjusting for the covariates. In men, there were significant genetic correlations between BMI and CCA-IMT (ρ(G)=0.32±0.11), BMI and ICA-IMT (ρ(G)=0.35±0.11) and WC and ICA-IMT (ρ(G)=0.32±0.13) after adjusting for covariates, whereas in women the cross-trait genetic correlations were no longer significant after adjusting for the covariates.In this Korean twins and families, we found sex-specific associations between adiposity and anthropometric measures and the IMT at each segment of the carotid artery, and BMI and WC in men can be indicators predicting carotid intima-media thickening regardless of age and CV risk factors.

Bone mineral density (BMD), a representative marker of osteoporosis risk, is found to be highly heritable in this Korean study, which is very consistent with the findings in Western populations. This finding strongly supports that genetic factors are significant determinants of osteoporosis risk along with individual biological and behavioral factors.Although genetic factors are known to contribute significantly to variations in BMD in Western populations, such an association has not been fully evaluated in an Asian population. This study was conducted to determine the role of genetic factors on BMD in Korean population.The study participants were 2,728 men and women consisting of 497 monozygotic (MZ) twin pairs, 119 dizygotic (DZ) twin pairs, and 1,496 first-degree relatives from the Healthy Twin Study. BMD was measured using dual-energy X-ray absorptiometry. Quantitative genetic analysis based on a variance decomposition model was performed.Age and the measured covariates accounted for 17~61% of the variation in BMD, depending on the sites of measurement. After accounting for the covariate effects, the heritability of BMD at the whole body, thoracic and lumbar spine, whole ribs, whole pelvis, whole arms, and whole legs were 0.76, 0.72, 0.73, 0.71, 0.51, and 0.75, respectively. The pair-wise correlation of BMD was the highest within MZ twin pairs, followed by DZ twin pairs, sibling pairs, and parents-child pairs. Cross-trait correlation analysis revealed a positive genetic correlation between BMDs at different sites, ranging from 0.80 (arm and leg BMD) to 0.50 (pelvis and arm BMD).The high heritability of BMD in this Korean population similar to those found in Western populations and the significant common genetic basis between BMDs at different sites strongly supports a significant role of genetic determinants on the risk of osteoporosis.

Endoscopic ultrasound (EUS)-assisted biliary access is utilized when conventional endoscopic retrograde cholangiopancreatography (ERCP) fails. We report a 10-year experience utilizing a transduodenal EUS rendezvous via a transpapillary route without dilation of the transduodenal tract, followed by immediate ERCP access. Patients included all EUS-guided rendezvous procedures for biliary access that were performed following ERCP failure. EUS-assisted bile duct puncture was performed via a transduodenal approach and a guide wire was advanced through the papilla without any dilation or bougienage of the tract; ERCP was performed immediately afterwards. EUS-assisted biliary rendezvous was attempted in 15 patients (mean age 66 +/- 18.2 years; malignant = 10, benign = 5). Mean diameter of measured bile ducts was 14.3 +/- 5.17 mm (range 4-23 mm). The reasons for initial ERCP failure were tumor infiltration or edema (n = 9), intradiverticular papilla (n = 2), pre-existing duodenal stent (n = 1), and anatomic anomalies (n = 3). Successful EUS-guided bile duct puncture and wire passage were achieved in all 15 patients (100 %), with drainage being successful in 12 / 15 (80 %). Failures occurred in three patients due to inability to traverse the biliary stricture (n = 2) or dissection of a choledochocele with the guide wire (n = 1); all were subsequently drained via percutaneous methods. Stents placed were metallic in eight patients and plastic in four. Complications consisted of moderate pancreatitis after a difficult ERCP attempt in one patient, and bacteremia after percutaneous biliary drainage in another. There were no instances of perforation, extraluminal air or fluid collections. EUS-assisted biliary drainage utilizing a transduodenal rendezvous approach demonstated a high success rate without any complications directly attributable to the EUS access. Advantages over percutaneous biliary and other methods of EUS biliary access include performance under the same anesthesia, and a very small-caliber needle puncture similar to EUS/fine-needle aspiration.

This study compared percutaneous sclerotherapy using 50% acetic acid with that using 99% ethanol for patients with simple renal cysts. The study included 72 simple renal cysts in 64 patients (male/female ratio = 31/33; age range, 31-75 years). Under fluoroscopic guidance, the cyst fluid was aspirated completely. Sclerotherapy was then performed using 50% acetic acid for 32 cysts and 99% ethanol for 40 cysts. The volumes of each renal cyst before and after sclerotherapy were compared using ultrasonography or CT. Medical records were reviewed to analyse any complications. The mean follow-up period was 21.5 months (range, 3-75 months). The mean remnant volume of the cyst after sclerotherapy was 2.6% of the initial volume in the acetic acid group and 14.0% in the ethanol group. The rates of complete remission, partial remission and treatment failure were 90.6%, 9.4% and 0%, respectively, in the acetic acid group, and 60.0%, 30.0% and 10.0%, respectively, in the ethanol group. There were no complications related to sclerotherapy in either group. In conclusion, acetic acid is a safe and effective sclerosing agent, with clinical results superior to those of ethanol, and is an alternative to ethanol for sclerotherapy of renal cysts.

Detailed, country‐specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7001000 cases) and Indonesia (3187000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

High-density lipoprotein cholesterol (HDLC) is anti-inflammatory in the basal state and pro-inflammatory during the acute-phase response. Blood mercury also has an inflammatory property. Therefore, the aim of this study was to investigate the relationship between serum HDLC and blood mercury concentration in relation with metabolic syndrome (MS). The data of 7616 subjects (3713 men and 3903 women), over 20 years of age, from 2008 to 2013, Korea National Health and Nutrition Examination Survey were selected for cross-sectional analyses. Correlation and regression of serum HDLC and blood mercury were initially done. We compared serum HDLC concentration according to blood mercury quartile after adjustment for relevant variables in subjects with MS. Mean blood mercury concentrations is 5.6 and 3.9 μg/dL in men and women, respectively. Blood mercury concentration in MS subjects was positively correlated with serum HDLC concentration, especially in men. In addition, HDLC concentration was significantly higher according to the higher blood mercury quartile. Serum HDLC was positively associated with blood mercury concentration in MS Korean men. Therefore, elevated blood mercury may be a factor to increase serum HDLC concentration in MS men.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV‐related mortality and morbidity. HCV‐related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV‐infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV‐related morbidity and mortality are to be achieved.

Overexpression of p16 is associated with improved outcomes among patients with oropharyngeal carcinoma. However, its role in the outcomes of patients with nasopharyngeal cancer (NPC) remains unclear.Eighty-six patients with NPC treated at MD Anderson Cancer Center from 2000 to 2014 were identified. Epstein-Barr virus (EBV) and human papillomavirus (HPV) status were determined by in situ hybridization (ISH) and p16 by immunohistochemical staining.EBV positivity was associated with extended overall survival (OS; median, 95.0 vs 44.9 months; p.004), progression-free survival (PFS; median, 80.4 vs 28.1 months; p.013), and locoregional control (median, 104.4 vs 65.5 months; p.043). In patients with EBV-positive tumors, p16 overexpression correlated with improved PFS (median, 106.3 vs 27.1 months; p.02) and locoregional control (median, 93.6 vs 64.5 months; p.02).P16 overexpression is associated with improved PFS and locoregional control in patients with EBV-positive NPC. P16 expression may complement EBV status in predicting treatment outcomes for patients with NPC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1459-E1466, 2016.

Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammation-associated diseases. Clusterin levels in childhood asthma have not been evaluated.(1) To evaluate sputum clusterin levels in children with asthma compared to a control group. (2) To assess the relationships between sputum clusterin levels and airway inflammation, pulmonary function, and bronchial hyperresponsiveness.This study included 170 children aged 5-18 years with stable asthma (n = 91), asthma exacerbation (n = 29), or no asthma (healthy controls; n = 50). Induced sputum, pulmonary function, and methacholine challenge tests were performed. Stable asthma was classified into two groups according to the severity. Clusterin levels in sputum were measured using an enzyme-linked immunosorbent assay.Children with stable asthma had a higher clusterin level than healthy controls [4540 (3872-5651) pg/mL vs. 3857 (1054-4369) pg/mL, P 0.001]. The clusterin level was also more elevated in eosinophil-dominant sputum than in non-eosinophilic sputum in stable asthma [5094 (4243-6257) pg/mL vs. 4110 (1871-4839) pg/mL, P = 0.0017]. Clusterin levels were associated with asthma severity. Paradoxically, clusterin levels were lower during asthma exacerbation than in stable asthma [1838 (350-4790] pg/mL vs. 4540 (3872-5651) pg/mL, P 0.001]. Clusterin levels were strongly correlated with the methacholine concentration that caused a 20% decrease in the forced expiratory volume in 1 s (r = -0.617, P 0.001); there was no significant correlation between clusterin levels and other pulmonary function parameters.Clusterin levels were altered in children with stable asthma and asthma exacerbation because of its antioxidant and anti-inflammatory effects. Clusterin may be a marker that reflects airway inflammation and severity of symptoms, and it can be used in the assessment and management of childhood asthma.

Intravenous or volatile agents reduce respiratory function, which can result in respiratory complications in geriatric patients. We hypothesised that there would be no differences in lung function between anaesthesia established using either drug.Elderly patients were randomly assigned to receive either propofol with remifentanil (n = 48) or desflurane (DES) with remifentanil (n = 52) for knee surgery. Spirometry tests including forced expiratory volume in 1 s (FEV1 ), forced vital capacity (FVC), forced mid-expiratory flow (FEF25-75), and FEV1 /FVC ratio were performed preoperatively, and 30 min, 60 min, and 24 h after awakening. Emergence time and post-operative pain scores were also measured.Time to emergence was significantly longer in the propofol than in the DES group (17.0 vs. 12.5 min, P = 0.04). Post-operative FEV1 (1.6 or 1.4 l, P = 0.68 between groups) were significantly lower than preoperative values (2.1 or 2.0 l, P = 0.001 vs. post-operative values, respectively) in both groups. Reduced FEV1 lasted for 24 h after surgery (1.7 or 1.6 l, P = 0.001 vs. preoperative values, respectively). Post-operative FVC or FEF25-75 were lower than preoperative values. FEV1 /FVC ratio did not change during the study period in both groups. There was no difference in FEV1 , FVC, FEF25-75, FEV1 /FVC, and post-operative pain between the two anaesthetic techniques.Although there is a delay in awakening when using propofol, the effects of propofol on post-operative spirometry parameters are similar to those of DES when anaesthesia duration is approximately 3 h. Decreased respiratory parameters persisted up to 24 h after anaesthesia, irrespective of the choice of anaesthetic.

BACKGROUND AND STUDY AIMS: We evaluated the therapeutic effects of percutaneous transhepatic photodynamic therapy (PDT) in patients with advanced bile duct cancer. The utility of intraductal ultrasonography (IDUS) for the assessment of responses and for regular follow up after PDT was also examined. METHODS: Percutaneous transhepatic biliary drainage (PTBD) was initiated before PDT. Following dilation and maturation of the PTBD tract, percutaneous PDT was performed. Intraluminal photoactivation was carried out using percutaneous cholangioscopy 2 days after intravenous application of a hematoporphyrin derivative. All patients were additionally provided with percutaneous bile duct drainage catheters after PDT. IDUS was conducted monthly to measure the thickness of the tumor mass before and after PDT. RESULTS: 24 patients with advanced cholangiocarcinomas (Bismuth IIIa, n = 4; IIIb, n = 10; IV, n = 10) were treated with PDT. At 3 months after PDT, the mean thickness of the tumor mass had decreased from 8.7 +/- 3.7 mm to 5.8 +/- 2.0 mm (P < 0.01). At 4 months after PDT, the thickness of the mass had increased to 7.0 +/- 3.7 mm. Quality of life indices improved dramatically and remained stable 1 month after PDT; the Karnofsky index increased from 39.1 +/- 11.36 to 58.2 +/- 22.72 points (P = 0.003). The 30-day mortality rate was 0 %, and the median survival time was 558 +/- 178.8 days (current range 62 - 810 days). CONCLUSIONS: PDT using percutaneous cholangioscopy is safe and effective for advanced hilar cholangiocarcinoma, and seems to prolong survival. IDUS is useful for evaluating changes in the thickness of the tumor mass after PDT.

Aims Transforming growth factor (TGF)-beta1 is a cytokine with both beneficial anti-inflammatory effects and detrimental profibrotic activity in the pathophysiology and progression of glomerulonephritides. The transcriptional activity of the gene for TGF-beta1 and the plasma levels of TGF-beta1 protein are associated with C-509T polymorphism at the promoter region, and with T869C (Leu 10Pro) polymorphism at codon 10, of the TGF-beta1 gene. Methods Using PCR-RFLP and the amplification refractory mutation system PCR, we investigated the C-509T and T869C polymorphisms, respectively, to elucidate whether allele frequency differences exist between IgA nephropathy (IgAN) patients who were followed up for at least 3 years (n = 108) and a normal population (n = 55). We also determined the correlations between the TGF-beta1 polymorphisms and the progression of IgAN. Results In C-509T polymorphism, there were significant differences in genotype frequency between IgAN patients and normal controls (CC: CT: TT, 20:29:33 vs. 11:31:13, chi2 = 6.299, p = 0.043). In Kaplan-Meier survival analysis, the patients with TT genotype showed a poorer renal survival than those with CC + CT genotypes (p = 0.042). In T869C polymorphism, there were also significant differences in genotype frequency between IgAN patients and normal controls (TT : TC : CC, 4 : 79 : 25 vs. 0 : 52 : 2, chi2 = 12.552, p = 0.002). The initial serum creatinine (Scr) level was higher in the patients with CC genotype than in those with TT + TC genotypes. In Kaplan-Meier survival analysis, the patients with CC genotype showed a poorer renal survival than those with TT + TC genotypes, but not to a statistically significant extent (p = 0.076). In the combined survival analyses, the high TGF-beta1 producer group showed a poor renal survival rate (p = 0.014). Conclusion Compared to normal population, the frequencies of genotypes producing high TGF-beta1 protein were higher in IgAN patients. Moreover, patients with genotypes producing high TGF-beta1 plasma levels showed a poor renal survival rate.

Rhinoplasty in the aging patient poses a unique set of challenges to the plastic surgeon. Aging patients usually have different expectations and motivations than their younger counterparts; therefore, open communication and frank discussions are paramount to define realistic goals. Anatomically, changes in skin quality, cartilage characteristics, underlying bony framework, and the nasal airways mandate special considerations to optimize the functional and aesthetic results. This review will present a practical approach to the management of the nose in the aging patient.

Limb salvage is a viable alternative to amputation in many cases of advanced sarcoma. The authors examined their experience with microvascular reconstruction of upper extremity defects after sarcoma resection, focusing on oncologic and functional outcomes. A retrospective analysis yielded 17 patients who underwent 18 free flap procedures and met the inclusion criteria. Most patients (71 percent, n = 12) had recurrent sarcoma at presentation to the authors' institution. Malignant fibrous histiocytoma was the most common pathologic subtype (n = 6). High-grade tumors were present in 94 percent of patients (n = 16). The free flap survival rate was 100 percent. The rectus abdominis flap was the most common free flap used (39 percent; n = 7). Local recurrence occurred in nine flaps (50 percent), and five patients ultimately required amputations. Six patients (35 percent) had distant recurrence. The mean Enneking score for limb function was 73 percent of the maximum (21.9 of 30). The 5-year disease-specific survival rate was 61.3 percent. In select patients with advanced upper extremity sarcoma undergoing limb salvage, microvascular flap reconstruction can provide reliable, safe coverage with reasonable preservation of function.

Distraction has proven to be a useful technique in cases of severe bone deficiency in the craniofacial skeleton. This is a report of its use in the treatment of a child affected by amniotic band sequence. This 5 year old Hispanic female presented with transverse deficiences of one lower extremity and both upper extremities. Additionally, she was missing the mandible and overlying soft tissue from ramus to ramus. Although free fibula transfer was a possibility, due to the presence of only one lower extremity, it was elected to utilize the technique of distraction. After preliminary bone grafting to unite these two hemimanibles, the bone graft was distracted bilaterally to create a neomandible. Following consolidation and removal of the distraction devices, the child was markedly improved despite what appeared to be a pathologic fracture in the region of the mandibular angle. Repeat distraction was planned.

An 81-year-old woman was admitted with epigastric pain and weight loss. She had been diagnosed with an intraductal papillary mucosal tumor (IPMT) 7 years previously, but had refused surgery for religious reasons. Esophagogastroduodenoscopy revealed a nodular, elevated lesion that was discharging mucin into the duodenal bulb and posterior wall of the upper body of the stomach. Endoscopic ultrasonography, abdominal computed tomography, and endoscopic retrograde cholangiography were carried out, and a highly invasive IPMT with simultaneous invasion of the stomach and duodenum was diagnosed.

Interleukin-8 (IL-8) plays an important role in the host immune response to Mycobacterium tuberculosis by recruiting inflammatory cells to the site of infection. Here, we investigated the role of pleural macrophages and mesothelial cells in the production of IL-8 in tuberculous pleurisy. Large concentrations of IL-8 were detected in tuberculous pleural effusions, but not in pleural effusions associated with congestive heart failure (CHF). Tuberculous pleural macrophages and M. tuberculosis-infected CHF pleural macrophages produced large concentrations of IL-8. When immunohistochemistry was performed on pleural tissues, antigenic IL-8 was detected in the mesothelial cells lining the tuberculous pleura. Direct stimulation of cultured CHF pleural mesothelial cells with M. tuberculosis induced IL-8 secretion. However, conditioned media from M. tuberculosis-infected pleural macrophages (CoMTB) induced greater mesothelial cell IL-8 secretion. Tumour necrosis factor-alpha (TNF-alpha) and IL-1beta induced mesothelial cell IL-8 mRNA expression, and neutralizing anti-TNF-alpha antibody and IL-1 receptor antagonist nearly completely obliterated CoMTB-induced mesothelial cell IL-8 mRNA expression and protein secretion. These findings demonstrate that both pleural macrophages and mesothelial cells produce IL-8 in tuberculous pleurisy, and cytokines produced by M. tuberculosis-infected macrophages mediate mesothelial cell IL-8 production.

Previous studies have provided evidence indicating that the nuclear orphan receptor RTR plays an important role during embryonic development and in spermatogenesis. In this study, we examine the expression of RTR in murine placenta and several human placental choriocarcinoma cell lines. Northern blot analysis showed high expression of RTR mRNA in placental tissue. In contrast to murine testis, which contains 7.4 and 2.3 kb transcripts, placental tissue expressed only the larger transcript. Examination of RTR expression in murine placental tissue by immunohistochemistry demonstrated the presence of RTR protein in the nuclei of giant trophoblasts and spongiotrophoblasts. RTR mRNA was also expressed in rat choriocarcinoma Rcho-1 cells and in the human placental choriocarcinoma cell lines BeWo, JAR, and JEG-3. In trophoblasts, RTR was co-expressed with the estrogen-related receptors ERR alpha and ERR beta. Giant trophoblast differentiation in Rcho-1 cells, characterized by induction of placental lactogen I (PL-I), was accompanied by a steady decrease in the expression of RTR mRNA and down-regulation of ERR beta expression while levels of ERR alpha mRNA did not change significantly. RTR was able to inhibit ERR alpha-mediated transactivation through the consensus RTR-response element (RTRE) likely by competing with ERR alpha for binding to the RTRE. These results suggest the possibility of cross-talk between RTR and ERR alpha receptor signalling pathways in trophoblasts.

The aim of this study was to describe the glycaemic and metabolic control and diabetes-related complications in type 1 and type 2 Asian patients.Data of diabetes patients from 230 diabetes centres in 12 Asian regions were collected on a retrospective-prospective basis through review of medical records, interview and laboratory assessments. Analysis of glycated haemoglobin (HbA1c) was carried out in central laboratories appointed by Bio-Rad. The data collection case record forms were scanned electronically.22177 patients with valid data made up the analysis population. Among patents with type 1 and type 2 diabetes, there was a higher proportion of women than men (53% vs. 47% for type 1 patients and 56% vs. 44% for type 2 diabetes). Hypertension (61%) and overweight (40% with BMIor = 25 kg/m2 were common in type 2 patients. Dyslipidaemia was also present in at least half of both types of patients. Control of glycaemia (mean HbA,1c and fasting blood glucose [FBG]) was poor in type 1 (9.9 +/- 2.5%; 10.2 +/- 5.2 mmol/l) and type 2 patients (8.5 +/- 2.0%; 8.9 +/- 3.4 mmol/l). Glycaemia in the majority of both types of patients fell short of those stipulated by various guidelines. In type 2 patients, glycaemia deteriorated (HbA1c7.5%, FBGor = 7.0 mmol/l) with duration of diabetes7 years. Both types of diabetes appear to share a similar high prevalence of complications of cataract, retinopathy and neuropathy, although the prevalence of cataract (27%) and neuropathy (35%) was higher in type 2 diabetes. Screening for microalbuminuria was not common.The Inadequate metabolic and hypertension control, especially in type 2 patients, needs to be addressed.

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer’s disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE. Chronic traumatic encephalopathy (CTE) and Alzheimer's disease share common disease mechanisms, according to recent research on human brains. Jeong-Sun Seo and colleagues from Seoul National University, South Korea, and Hoon Ryu, Ann McKee and collegues from Boston University, USA sequenced all the RNA found in post-mortem brain tissue taken from six people with CTE, a progressive neurodegenerative disorder caused by repeated blows to the head, and compared the expression profile with seven normal control individuals. The researchers found that genes in two important signaling pathways were significantly less active in people with CTE. Altered expression of certain genes in these pathways suggested that the buildup of the aberrant tau protein in CTE occurs by a similar mechanism to that seen in Alzheimer's disease. Experiments in cell lines and mouse models substantiated this finding.

Intraoperative experience is an essential element of surgical training, but has the potential to impact patient outcomes. The purpose of this study was two-fold: 1) to evaluate the effect of resident involvement on morbidity and mortality following otolaryngology procedures and 2) to examine the influence of resident training level on the same outcomes.Retrospective cohort study.This study reviewed 2,320,920 patients captured in the 2005 to 2012 National Surgical Quality Improvement Program databases to identify surgical otolaryngology cases. Outcomes of interest included surgical complications, medical complications, and mortality. Cases with and without resident involvement were propensity matched (caliper = 0.2) to account for nonrandomized assignment, and data were subject to multivariate logistic regression analyses.Residents participated in 38.4% of the 20,307 cases identified. Cases with resident involvement demonstrated longer operative duration (178.8 minutes vs. 80.1 minutes, P.001), increased surgical complexity (23.5 relative value units [RVU] vs. 12.4 RVU, P.001) and greater overall morbidity burden. Logistic regression analyses of the matched cohort revealed that resident participation did not independently increase morbidity (odds ratio [OR] = 0.969, P = .751) or mortality (OR = 0.893, P = .758). A separate logistic regression analysis of the unmatched cohort using resident postgraduate year showed that training level did not confer differential risk to patients.Our data indicate that resident involvement does not increase the risk of morbidity or mortality, and that trainees are being assigned to appropriate cases for their level of experience. These findings suggest that the contemporary paradigm of graduate otolaryngology surgical education does not negatively impact patient outcomes.2c Laryngoscope, 126:602-607, 2016.

BACKGROUND The prevalence and economic burden of chronic obstructive pulmonary disease (COPD) are increasing worldwide. However, little information is available concerning COPD-associated health care use and costs in Korea. OBJECTIVE To analyse 1) health care use, medical costs and medication use in 2009, and 2) changes in costs and medication use over 5 years (2006-2010). DESIGN Using the database of the Korean Health Insurance Review and Assessment Service, COPD patients were identified by searching on both ICD-10 codes and COPD medication. RESULTS A total of 192,496 COPD patients were identified in 2009. Total medical costs per person were US$2803 ± 3865; the average annual number of days of out-patient care and days of hospitalisation were respectively 40 ± 36 and 11 ± 33. Methylxanthine and systemic beta-agonists were the most frequently used drugs. However, the number of prescriptions for long-acting muscarinic antagonist increased rapidly. The total cost of COPD-related medications increased by 33.1% over 5 years. CONCLUSION The present study provides new insight into health care use and the economic burden of COPD in Korea. Changing patterns of COPD-related medication use could help inform COPD management policies.

Local cytokine concentrations are required for inhibition of tumor growth with less toxic side-effects. However, genetically engineered tumor cells secreting cytokines still induce toxicity and activate bystander cells. To circumvent such problems, membrane-bound forms of IL-4 (IL-4m) were expressed on MethA fibrosarcoma tumor cells. Chimeric forms of IL-4 with the type I transmembrane protein CD4 or type II transmembrane protein TNF were designed to express IL-4 in opposite orientations on the tumor cell surface. The IL-4m on tumor clones was able to support cell growth of the IL-4 dependent cytotoxic cell line (CT.4S) and the Th2 cell clone (D10). Furthermore, the IL-4m tumor clones stimulated proliferation of 2C TCR transgenic spleen cells which are responsive to Ld MHC class I molecules. Expression of the IL-4/TNF chimeric protein on MethA cells elicited antitumor immunity and protected from MethA tumor challenge. The proposed tumor vaccine may serve as an effective gene therapy method to avoid the toxicity of recombinant cytokines and bulk bystander leukocyte stimulation encountered in conventional cytokine gene therapy.

OBJECTIVE: The goal of this study was to determine the feasibility and outcomes of percutaneously implantable catheter-port system placement in the hepatic artery for the purpose of intraarterial chemotherapeutic infusion. CONCLUSION: Percutaneously implantable catheter-port system placement is safe and technically feasible for use in the hepatic artery. The implantation procedure is less invasive than surgical implantation of similar port systems.

Reduction mammaplasty is commonly performed in women who are considered obese by the body mass index (BMI) classification of the World Health Organization.The authors compare complication rates among breast reduction patients, stratified by BMI, across multiple institutions.A retrospective analysis was performed of all reduction mammaplasties in the database of the National Surgical Quality Improvement Program for 2006 through 2010. Demographic, comorbidity, and BMI data were collected. Data on medical and surgical complications, reoperation, and mortality were collected through 30 days postsurgery.Of 2492 patients, 55% were considered obese (BMI30). The overall rate of surgical complications was 4.0%, increasing from 2.4% for BMI25 to 7.1% for BMI45 (P = .006), with an adjusted odds ratio of 2.97 for BMI45 versus BMI25. The most common surgical complication was superficial surgical site infection; it was found in 2.9% of patients, increasing from 2.1% for BMI25 to 5.1% for BMI45 (P = .03). The medical complication rate was 0.6%, and the reoperation rate was 2.1%. There were no deaths. A maximal point analysis showed that BMI ≥39 was associated with a significantly higher complication rate, with an odds ratio of 2.38.Reduction mammaplasty is a safe surgical procedure, even when performed on obese patients. However, patients with higher BMI have a greater risk of surgical site complications. This risk should be discussed preoperatively with obese patients.

BACKGROUND Recent health care legislation institutes penalties for surgical readmissions secondary to complications. There is a paucity of evidence describing risk factors for readmission after breast reconstruction procedures. METHODS Patients undergoing breast reconstruction in 2011 were identified in the National Surgical Quality Improvement Program database. Patients were grouped as purely immediate implant/tissue-expander reconstructions or purely autologous reconstruction for analysis. Reconstructions involving multiple types of procedures were excluded due to difficulty with classification. Perioperative variables were analyzed using χ and Student t test as appropriate. Multivariate regression modeling was used to identify risk factors for readmission. RESULTS Of 5012 patients meeting inclusion criteria, 3960 and 1052 underwent implant/expander and autologous reconstructions, respectively. Implant/expander and autologous cohorts experienced similar readmission rates (4.34% vs 5.32%, respectively; P = 0.18). However, autologous reconstructions experienced a higher rate of overall complications than implant/expander reconstructions (19.96% vs 5.86%, respectively; P < 0.05), as well as higher rates of reoperation (9.7% vs 6.5%, respectively; P < 0.05). Common predictors of readmission for implant/expander and autologous cohorts included operative time, American Society of Anesthesiologist class 3 and 4, and superficial surgical site infection. Smoking, sepsis, deep wound infection, organ space infection, and wound disruption were predictive of readmission for implant/expander reconstruction only, whereas hypertension was predictive of readmission after autologous reconstruction only. CONCLUSIONS This is the first study of readmission rates after breast reconstruction. Knowledge of specific risk factors for readmission may improve patient outcomes, steer strategies for optimizing reconstructive outcomes, and minimize readmissions.

Unplanned readmissions serve as a marker for health care quality. Risk factors associated with unplanned readmission after microvascular free tissue transfer have never been examined. In this study, we sought to identify perioperative predictors of 30-day unplanned readmission in free flap patients.The National Surgical Quality Improvement Program (NSQIP) database was retrospectively reviewed to identify all patients who underwent microvascular free tissue transfer in 2011. Multivariate logistic regression models were used to estimate independent predictors of unplanned readmission.Among free flap patients, unplanned readmission rate was 7.9%. In multivariate analysis, the only factor that significantly predicted unplanned readmission (P 0.05) was open wound/wound infection (odds ratio [OR] 2.71). Postoperative variables significantly associated with unplanned readmission included surgical complications (OR 5.43), medical complications (OR 5.62), and unplanned reoperation (OR 3.94). Flap failure was not associated with unplanned readmission.In our study, the presence of either open wound/wound infection, development of surgical complications, medical complications, and unplanned reoperations were associated with unplanned readmissions. Further research in predictive factors is suggested to avoid costly, unnecessary, and preventable readmissions.

Thrombosis is a common cause of flap failure in microvascular tissue transfer, which questions the effects of anemia on this outcome. This article seeks to contribute a large, multi-institutional data analysis to this debate.Free tissue transfer patients were identified in the National Surgical Quality Improvement database through a specified Current Procedural Terminology algorithm. Bivariate analysis compared anemic and nonanemic groups with respect to flap failure and other outcomes. Multivariable logistic regression was used to determine risk factors for flap failure.Of the 864 patients who met inclusion criteria, 244 were anemic and 620 were not. Bivariate analysis showed no significant difference between groups with respect to flap failure (3.28% vs. 4.03%, P = 0.0603). Multivariate regression analysis supported this (OR 95% CI = 0.371-1.912).These findings, based on the largest sample in the literature, show anemia is neither a predictor of free tissue transfer failure nor is it protective.

In 1994 the first heat shock protein 90 (Hsp90) inhibitor was identified and Hsp90 was reported to be a target for anticancer therapeutics. In the past 18 years there have been 17 distinct Hsp90 inhibitors entered into clinical trial, and the small molecule Hsp90 inhibitors have been highly valuable as probes of the role of Hsp90 and its client proteins in cancer. Although no Hsp90 inhibitor has achieved regulatory approval, recently there has been significant progress in Hsp90 inhibitor clinical development, and in the past year RECIST responses have been documented in HER2-positive breast cancer and EML4-ALK-positive non-small cell lung cancer. All of the clinical Hsp90 inhibitors studied to date are specific in their target, i.e. they bind exclusively to Hsp90 and two related heat shock proteins. However, Hsp90 inhibitors are markedly pleiotropic, causing degradation of over 200 client proteins and impacting critical multiprotein complexes. Furthermore, it has only recently been appreciated that Hsp90 inhibitors can, paradoxically, cause transient activation of the protein kinase clients they are chaperoning, resulting in initiation of signal transduction and significant physiological events in both tumor and tumor microenvironment. An additional area of recent progress in Hsp90 research is in studies of the posttranslational modifications of Hsp90 itself and Hsp90 co-chaperone proteins. Together, a picture is emerging in which the impact of Hsp90 inhibitors is shaped by the tumor intracellular and extracellular milieu, and in which Hsp90 inhibitors impact tumor and host on a microenvironmental and systems level. Here we review the tumor intrinsic and extrinsic factors that impact the efficacy of small molecules engaging the Hsp90 chaperone machine.