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The development of suitable methods to deliver peptides specifically to the endoplasmic reticulum (ER) can provide some potential therapeutic applications of such peptides. Ankylosing spondylitis (AS) is strongly associated with the expression of human leukocytic antigen-B27 (HLA-B27). HLA-B27 heavy chain (HC) has a propensity to fold slowly resulting in the accumulation of misfolded HLA-B27 HC in the ER, triggering the unfolded protein response, and forming a homodimer, (B27-HC)2. Natural killer cells and T-helper 17 cells are then activated, contributing to the major pathogenic potentials of AS. The HLA-B27 HC is thus an important target, and delivery of an HLA-B27-binding peptide to the ER capable of promoting HLA-B27 HC folding is a potential mechanism for AS therapy. Here, we demonstrate that a His6-ubiquitin-tagged Tat-derived peptide (THU) can deliver an HLA-B27-binding peptide to the ER promoting HLA-B27 HC folding. The THU-HLA-B27-binding peptide fusion protein crossed the cell membrane to the cytosol through the Tat-derived peptide. The HLA-B27-binding peptide was specifically cleaved from THU by cytosolic ubiquitin C-terminal hydrolases and subsequently transported into the ER by the transporter associated with antigen processing. This approach has potential application in the development of peptide therapy for AS.

Background: Newborn anogenital distance (AGD) has been associated with prenatal exposure of phthalates. The association between prenatal phthalate exposure and sex steroid hormones in newborns is unclear. Object: This study aimed to examine whether cord-blood sex hormone levels were associated with prenatal phthalate exposure and newborn anogenital distance (AGD). Methods: In the Taiwan Maternal and Infant Cohort Study, we recruited 1,676 pregnant women in their third trimester in 2012–2015 in Taiwan. We determined 11 urinary phthalate metabolites in pregnant women, three maternal and five cord-blood steroid sex-hormone concentrations. Five hundred and sixty-five mother-infant pairs with sufficient data were included. Trained neonatologists measured 263 newborns' AGD. We examined the associations of prenatal phthalate metabolite levels with AGD and hormones using linear regression models and evaluated correlations between maternal and cord-blood sex hormone levels and AGD. Results: Compared with the male newborns exposed to maternal phthalate metabolites at the first tertile, AGD was -3.75, -3.43, and -3.53 mm shorter among those exposed at the median tertile of di-2-ethylhexyl phthalate (DEHP) metabolites, monobenzyl phthalate (MBzP), and monomethyl phthalate (MMP), respectively. Compared with those who had exposed at the first tertile, cord-blood follicle-stimulating hormone (FSH) decreased among male newborns exposed at higher levels of MMP, mono-n-butyl phthalate (MnBP), MBzP and DEHP, and among female newborns exposed at higher levels of MMP, MBzP and mono(2-ethyl-5-hydroxyhexyl) phthalate. However, we did not observe significant correlations of maternal or cord-blood sex steroid hormones with newborns' AGDs. Conclusions: Alterations in cord-blood sex steroid hormone levels were associated with prenatal phthalate exposures, particularly in male newborns. Women aspiring to be pregnant should be alerted of the need of reducing phthalate exposure. [ABSTRACT FROM AUTHOR]

Background: To compare the infection rates between cetuximab-treated patients with head and neck cancers (HNC) and untreated patients. Methodology: A national cohort of 1083 HNC patients identified in 2010 from the Taiwan National Health Insurance Research Database was established. After patients were followed for one year, propensity score analysis and instrumental variable analysis were performed to assess the association between cetuximab therapy and the infection rates. Results: HNC patients receiving cetuximab (n = 158) were older, had lower SES, and resided more frequently in rural areas as compared to those without cetuximab therapy. 125 patients, 32 (20.3%) in the group using cetuximab and 93 (10.1%) in the group not using it presented infections. The propensity score analysis revealed a 2.3-fold (adjusted odds ratio [OR] = 2.27; 95% CI, 1.46-3.54; P = 0.001) increased risk for infection in HNC patients treated with cetuximab. However, using IVA, the average treatment effect of cetuximab was not statistically associated with increased risk of infection (OR, 0.87; 95% CI, 0.61-1.14). Conclusions: Cetuximab therapy was not statistically associated with infection rate in HNC patients. However, older HNC patients using cetuximab may incur up to 33% infection rate during one year. Particular attention should be given to older HNC patients treated with cetuximab. [ABSTRACT FROM AUTHOR]

Background: Dementia increases the risk of death in older patients hospitalized for acute illnesses. However, the effect of dementia on the risks of developing acute organ dysfunction and severe sepsis as well as on the risk of hospital mortality in hospitalized older patients remains unknown, especially when treatments for these life-threatening situations are considered. Methods: In this population-based cohort study, we analyzed 41,672 older ($65 years) patients, including 3,487 (8.4%) with dementia, from the first-time admission claim data between 2005 and 2007 for a nationally representative sample of one million beneficiaries enrolled in the Taiwan National Health Insurance Research Database. Outcomes included acute organ dysfunction, severe sepsis, and hospital mortality. The effect of dementia on outcomes was assessed using multivariable logistic regression. Results: Dementia was associated with a 32% higher risk of acute organ dysfunction (adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.19- 1.46), a 50% higher risk of severe sepsis (aOR 1.50, 95% CI 1.32- 1.69) and a 28% higher risk of hospital mortality (aOR 1.28, 95% CI 1.10-1.48) after controlling age, sex, surgical condition, comorbidity, principal diagnosis, infection status, hospital level, and length of hospital stay. However, the significant adverse effect of dementia on hospital mortality disappeared when life-support treatments, including vasopressor use, hemodialysis, mechanical ventilation, and intensive care, were also controlled. Conclusions: In hospitalized older patients, the presence of dementia increased the risks of acute organ dysfunction, severe sepsis and hospital mortality. However, after intervention using life-support treatments, dementia only exhibited a minor role on short-term mortality. [ABSTRACT FROM AUTHOR]

BACKGROUND:Chronic lymphocytic leukemia (CLL) is incurable through conventional chemoimmunotherapy regimens. Despite durable responses to front-line therapy and sustained remission rates in patients with CLL, a majority of patients eventually relapse in 5 years of initial treatment. The depth of the response may affect the length of response. Maintenance therapies were aimed to deep remissions and extend the period of disease quiescence. Lenalidomide, rituximab and ofatumumab had demonstrated some efficacy as a maintenance therapy compared to no intervention for CLL patients. The relative effect on disease control and safety between different maintenance therapies were unclear. METHODS:We performed a systematic literature review and network meta-analysis to evaluate relative effect on disease control and safety of current available maintenance therapies. We searched PubMed, Embase and Cochrane database up to March 6, 2019. Relevant reference of review article and conference abstract including European Hematology Association Annual Meeting (EHA 2018), American Society of Hematology Annual Meeting (ASH 2018) and American Society of Clinical Oncology Annual Meeting (ASCO 2018) were searched. Randomized controlled trials (RCT) involving current available maintenance therapy including "Lenalidomide", "Rituximab", "Ofatumumab", "Ibrutinib", "Idelalisib", "Venetoclax"and "Obinutuzumab"were eligible. Outcomes of interest included progression-free survival (PFS), overall survival (OS) and serious adverse events (SAE) in CLL patients received subsequent maintenance therapy. Two authors CHL and CL) independently assessed eligibility for all identified citations and extracted data from the original trial reports. The selected studies' risk of bias was assessed following the guidelines of Cochrane Collaboration Handbook. RESULTS:In total, six phase III RCTs with total 1,615 CLL patients were identified. Maintenance therapy using lenalidomide, rituximab, and ofatumumab demonstrated a statistically significant effect in prolongation of progression-free survival (HR:0.37, 95% CI: 0.27-0.50 of lenalidomide; HR:0.50, 95% CI: 0.38-0.66 of rituximab; HR:0.52, 95% CI:0.41-0.66 of ofatumumab, separately) compared with no intervention; however, for overall survival, the effect of maintenance therapy showed no significant difference versus no intervention (HR: 0.89, 95% CI: 0.70-1.14). Lenalidomide showed the best efficacy for PFS (HR: 0.37, 95% CI: 0.27-0.50, Probability of being best treatment: 96%). CONCLUSIONS:Our network meta-analysis provided an integrated overview of relative efficacy and safety of different maintenance therapies in CLL. All maintenance therapies were effective in reducing the risk of disease progression versus no intervention. Based on current best evidence, maintenance therapy with lenalidomide is the most efficacious option.

Although proton magnetic resonance spectroscopy (1H-MRS) is a common method for the evaluation of intracranial meningiomas, controversy exists regarding which parameter of 1H-MRS best predicts the histopathological grade of an intracranial meningioma. In this study, we evaluated the results of pre-operative 1H-MRS to identify predictive factors for high-grade intracranial meningioma. Thirteen patients with World Health Organization (WHO) grade II-III meningioma (confirmed by pathology) were defined as high-grade; twenty-two patients with WHO grade I meningioma were defined as low-grade. All patients were evaluated by 1H-MRS before surgery. The relationships between the ratios of metabolites (N-acetylaspartate [NAA], creatine [Cr], and choline [Cho]) and the diagnosis of high-grade meningioma were analyzed. According to Mann-Whitney U test analysis, the Cho/NAA ratio in cases of high-grade meningioma was significantly higher than in cases of low-grade meningioma (6.34 ± 7.90 vs. 1.58 ± 0.77, p

Studies on vitrectomy with and without internal limiting membrane (ILM) peeling for idiopathic epiretinal membrane (ERM) have yielded uncertain results regarding clinical outcomes and recurrence rates.To compare the clinical outcomes of vitrectomy with and without ILM peeling for idiopathic ERM.Databases, including PubMed, Embase, Cochrane, Web of Science, Google Scholar, CNKI databases, FDA.gov, and ClinicalTrials.gov, published until July 2016, were searched to identify studies comparing the clinical outcomes following vitrectomy with ERM and ILM peeling and with only ERM peeling, for treating idiopathic ERM. Studies with sufficient data were selected. Pooled results were expressed as mean differences (MDs) and risk ratios (RRs) with corresponding 95% confidence intervals (CI) for vitrectomy with and without ILM peeling with regard to postoperative best corrected visual acuity (BCVA), central retinal thickness (CRT), and ERM recurrence rate.Eleven retrospective studies and one randomized controlled trial involving 756 eyes were identified. This demonstrated that the postoperative BCVA within 12 months was significantly better in the non-ILM peeling group (MD = 0.04, 95% CI: 0.00 to 0.08; P = 0.0460), but that the patients in the ILM peeling group had significantly better postoperative BCVA after 18 months (MD = -0.13, 95% CI: -0.23 to -0.04; P = 0.0049) than did those in the non-ILM peeling group. The non-ILM peeling group exhibited a higher reduction in postoperative CRT (MD = 51.55, 95% CI:-84.23 to -18.88; P = 0.0020) and a higher recurrence rate of ERM (RR = 0.34, 95% CI:0.16 to 0.72; P = 0.0048) than did the ILM peeling group. However, the improvement rates of BCVA (RR = 1.03, 95% CI:0.72 to 1.47; P = 0.8802) and postoperative CRTs (MD = 18.15, 95% CI:-2.29 to 38.60; P = 0.0818) were similar between the two groups.Vitrectomy with ILM peeling results in better visual improvement in long-term follow-ups and lower ERM recurrence rates, and vitrectomy with only ERM peeling is more efficacious in reduction of CRT than is vitrectomy with ILM peeling.

Current studies that compare the efficacy and safety of micafungin (MCFG) with that of triazoles for the prophylaxis and treatment of invasive fungal infections (IFIs) demonstrate a lack of sufficient evidence and yield conflicting results. To compare the efficacy and safety of MCFG and triazoles in the prevention and treatment of IFIs, we conducted a meta-analysis and trial sequential analysis (TSA).For the meta-analysis, we systematically searched the databases of PubMed, Embase and Cochrane Central Register of Controlled Trials and relevant database articles for randomized controlled studies published through November 2016. Comparative studies of the efficacy and safety of MCFG versus triazoles in the prevention and treatment of IFIs were selected. Meta-analysis was performed by R software with the "metafor" package. Pooled results were expressed as risk ratios (RRs) with corresponding 95% confidence intervals (CI). TSA was adopted to assess the studies' power with TSA version 0.9 beta.Nine current studies were included in the meta-analysis (1049 cases and 959 controls). Pooled trial comparisons indicated that MCFG does have significantly higher treatment success rates (RR = 1.13; 95% CI, 1.02-1.25; p = 0.0205) and reduces the number of overall IFIs (RR = 0.75; 95% CI, 0.61-0.92; p = 0.0056). However, MCFG demonstrates no difference in all-cause mortality (RR = 0.76; 95% CI, 0.52-1.12, p = 0.1624). For the safety evaluation, MCFG had a significantly lower incidence of severe adverse events (AEs) (RR = 0.45; 95% CI, 0.25-0.83; p = 0.0105), hepatic impairment (RR = 0.70; 95% CI, 0.50-0.97; p = 0.0363) and premature discontinuation (RR = 0.51; 95% CI, 0.34-0.76, p = 0.0010). Meta-regression analysis disclosed the correction of mean age and treatment success rates (P < 0.0001). Meanwhile, TSA demonstrated sufficient power to show efficacy.The treatment success rate of MCFG is superior to that of triazoles for the prophylaxis and treatment of IFIs, and correction of the mean patient age demonstrates that efficacy increases as patient age decreases. MCFG appears to be well-tolerated with manageable side effects and lower withdrawal rates. However, additional clinical trials should be conducted on specific drug-related mortality and AEs to gather sufficient evidence on these matters.

We conducted a retrospective study to investigate the anesthesia-controlled time and factors that contribute to prolonged extubation in open colorectal surgery. Using our hospital database, demographic data, various time intervals (waiting for anesthesia time, anesthesia time, surgical time, emergence time, exit from operating room after extubation, total operating room time, and post-anesthesia care unit stay time), and incidence of prolonged extubation (≥ 15 mins), were compared between patients who received desflurane/fentanyl-based anesthesia and total intravenous anesthesia via target-controlled infusion with fentanyl/propofol. Logistic regression analyses were performed to assess the association between variables that contributed to prolonged extubation. In conclusion, the anesthesia-controlled time was similar in desflurane anesthesia and propofol-based total intravenous anesthesia for open colorectal surgery in our hospital. Surgical time greater than 210 minutes, as well as age, contributed to prolonged extubation.

BACKGROUND:Studies of angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and the risks of knee osteoarthritis (OA) have yielded conflicting results. OBJECTIVE:To determine the association between ACE I/D and knee OA, we conducted a combined case-control study and meta-analysis. METHODS:For the case-control study, 447 knee OA cases and 423 healthy controls were recruited between March 2010 and July 2011. Knee OA cases were defined using the Kellgren-Lawrence grading system, and the ACE I/D genotype was determined using a standard polymerase chain reaction. The association between ACE I/D and knee OA was detected using allele, genotype, dominant, and recessive models. For the meta-analysis, PubMed and Embase databases were systematically searched for prospective observational studies published up until August 2015. Studies of ACE I/D and knee OA with sufficient data were selected. Pooled results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for the D versus I allele with regard to knee OA risk. RESULTS:We found no significant association between the D allele and knee OA [OR: 1.09 (95% CI: 0.76-1.89)] in the present case-control study, and the results of other genetic models were also nonsignificant. Five current studies were included, and there were a total of six study populations after including our case-control study (1165 cases and 1029 controls). In the meta-analysis, the allele model also yielded nonsignificant results [OR: 1.37 (95% CI: 0.95-1.99)] and a high heterogeneity (I2: 87.2%). CONCLUSIONS:The association between ACE I/D and knee OA tended to yield negative results. High heterogeneity suggests a complex, multifactorial mechanism, and an epistasis analysis of ACE I/D and knee OA should therefore be conducted.

Conventional genome-wide association studies (GWAS) have been proven to be a successful strategy for identifying genetic variants associated with complex human traits. However, there is still a large heritability gap between GWAS and transitional family studies. The "missing heritability" has been suggested to be due to lack of studies focused on epistasis, also called gene-gene interactions, because individual trials have often had insufficient sample size. Meta-analysis is a common method for increasing statistical power. However, sufficient detailed information is difficult to obtain. A previous study employed a meta-regression-based method to detect epistasis, but it faced the challenge of inconsistent estimates. Here, we describe a Markov chain Monte Carlo-based method, called "Epistasis Test in Meta-Analysis" (ETMA), which uses genotype summary data to obtain consistent estimates of epistasis effects in meta-analysis. We defined a series of conditions to generate simulation data and tested the power and type I error rates in ETMA, individual data analysis and conventional meta-regression-based method. ETMA not only successfully facilitated consistency of evidence but also yielded acceptable type I error and higher power than conventional meta-regression. We applied ETMA to three real meta-analysis data sets. We found significant gene-gene interactions in the renin-angiotensin system and the polycyclic aromatic hydrocarbon metabolism pathway, with strong supporting evidence. In addition, glutathione S-transferase (GST) mu 1 and theta 1 were confirmed to exert independent effects on cancer. We concluded that the application of ETMA to real meta-analysis data was successful. Finally, we developed an R package, etma, for the detection of epistasis in meta-analysis [etma is available via the Comprehensive R Archive Network (CRAN) at https://cran.r-project.org/web/packages/etma/index.html].

Extensive genetic studies have identified a large number of causal genetic variations in many human phenotypes; however, these could not completely explain heritability in complex diseases. Some researchers have proposed that the "missing heritability" may be attributable to gene-gene and gene-environment interactions. Because there are billions of potential interaction combinations, the statistical power of a single study is often ineffective in detecting these interactions. Meta-analysis is a common method of increasing detection power; however, accessing individual data could be difficult. This study presents a simple method that employs aggregated summary values from a "case" group to detect these specific interactions that based on rare disease and independence assumptions. However, these assumptions, particularly the rare disease assumption, may be violated in real situations; therefore, this study further investigated the robustness of our proposed method when it violates the assumptions. In conclusion, we observed that the rare disease assumption is relatively nonessential, whereas the independence assumption is an essential component. Because single nucleotide polymorphisms (SNPs) are often unrelated to environmental factors and SNPs on other chromosomes, researchers should use this method to investigate gene-gene and gene-environment interactions when they are unable to obtain detailed individual patient data.

Renal failure is a common morbidity in multiple myeloma (MM). Although proteinuria has been increasingly reported in malignancies, it is not routinely used to refine risk estimates of survival outcomes in patients with MM. Here we aimed to investigate initial serum albumin and 24-hour daily protein excretion (24-h DPE) before treatment as prognostic factors in patients with MM. We conducted a retrospective analysis of 102 patients with myeloma who were ineligible for haematopoietic stem cell transplantation between October 2000 and December 2012. Initial proteinuria was assessed before treatment by quantitative analysis of 24-hour urine samples. The demographic and laboratory characteristics, survival outcome, and significance of pre-treatment 24-h DPE and albumin in the new staging system of MM were analyzed. Pre-treatment proteinuria (>300 mg/day) was present in 66 patients (64.7%). The optimal cut-off value of 24-h DPE before treatment was 500 mg/day. Analysis of the time-dependent area under the curve showed that the serum albumin and 24-h DPE before treatment were better than 24-h creatinine clearance rate and β2-microglobulin. A subgroup analysis showed that an initial excess proteinuria (24-h DPE ≥ 500 mg) was associated with poor survival status (17.51 vs. 34.24 months, p = 0.002). Furthermore, initial serum albumin was an independent risk factor on multivariate analysis (

BACKGROUND: Associations between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and chronic kidney disease (CKD) have been extensively studied, with most studies reporting that individuals with the D allele have a higher risk. Although some factors, such as ethnicity, may moderate the association between ACE I/D polymorphisms and CKD risk, gender-dependent effects on the CKD risk remain controversial. OBJECTIVES: This study investigated the gender-dependent effects of ACE I/D polymorphisms on CKD risk. DATA SOURCES: PubMed, the Cochrane library, and EMBASE were searched for studies published before January 2013. STUDY ELIGIBILITY CRITERIA PARTICIPANTS AND INTERVENTIONS: Cross-sectional surveys and case-control studies analyzing ACE I/D polymorphisms and CKD were included. They were required to match the following criteria: age >18 years, absence of rare diseases, and Asian or Caucasian ethnicity. STUDY APPRAISAL AND SYNTHESIS METHODS: The effect of carrying the D allele on CKD risk was assessed by meta-analysis and meta-regression using random-effects models. RESULTS: ETHNICITY [ODDS RATIO (OR): 1.24; 95% confidence interval (CI): 1.08-1.42] and hypertension (OR: 1.55; 95% CI: 1.04-2.32) had significant moderate effects on the association between ACE I/D polymorphisms and CKD risk, but they were not significant in the diabetic nephropathy subgroup. Males had higher OR for the association between ACE I/D polymorphisms and CKD risk than females in Asians but not Caucasians, regardless of adjustment for hypertension (p

Hepatic metastases are diagnosed synchronously in 3-14% of patients with gastric cancer, and metachronously in up to 37% of patients following ''curative" gastrectomy. Most patients who have gastric cancer and hepatic metastasis are traditionally treated with palliative chemotherapy. The impact of liver resection is still controversial. We attempted to assess whether liver resection can improve survival in cases of metachronous hepatic metastases from gastric cancer through a nationwide database.We conducted a nationwide cohort study using a claims dataset from Taiwan's National Health Insurance Research Database (NHIRD). We identified all patients with gastric cancer (diagnostic code ICD-9: 151.x) from the Registry for Catastrophic Illness Patient Database (RCIPD) of the NHIRD who received gastrectomy and as well as those with metachronous (≥180 days after gastrectomy) liver metastases (ICD-9 code: 197.7) between 1996/01/01 and 2012/12/31. Patients with other malignancies, with metastasis in the initial admission for gastrectomy and with other metastases were excluded. They were divided into two groups, liver resection group and non-resection group. All patients were followed till 2013/12/31 or withdrawn from the database because of death.653 patients who fullfilled the inclusion criteria were included in the research. They were divided into liver resection group (34 patients) and non-resection group (619 patients). There were no differences between the two groups in gender, Charlson Comorbidity index and major coexisting disease. Kaplan-Meier analysis demostrated the liver resection group had significantly better overall survival than the non-resection group. (1YOS: 73.5% vs. 19.7%, 3YOS: 36.9% vs. 6.6%, 5YOS: 24.5.3% vs. 4.4%, p

BackgroundOral squamous cell carcinoma (OSCC) is one of the most common malignant neoplasms in Taiwan. Activation of the mTOR signaling pathway has been linked to decreased radiation responsiveness in human oral cancer, thus it limits efficacy of radiotherapy. To address this question, we investigated the effect of AZD2014, a novel small molecular ATP-competitive inhibitor of mTORC1 and mTORC2 kinase, as a radiosensitizer in primary OSCC and OSCC-derived cell line models.MethodsWe isolated primary tumor cells from OSCC tissues and cell lines. AZD2014 was administered with and without ionizing radiation. The radiosensitizing effect of AZD2014 were then assessed using cell viability assays, clonogenic survival assays, and cell cycle analyses. Western blotting was used to detect protein expression.ResultsCombination treatment with AZD2014 and irradiation resulted in significant reduction in OSCC cell line and primary OSCC cell colony formation due to the enhanced inhibition of AKT and both mTORC1 and mTORC2 activity. Pre-treatment with AZD2014 in irradiated oral cancer cells induced tumor cell cycle arrest at the G1 and G2/M phases, which led to disruption of cyclin D1-CDK4 and cyclin B1-CDC2 complexes. Moreover, AZD2014 synergized with radiation to promote both apoptosis and autophagy by increasing caspase-3 and LC3 in primary OSCC cells.ConclusionsThese findings suggest that in irradiated OSCC cells, co-treatment with AZD2014, which targets mTORC1 and mTORC2 blockade, is an effective radiosensitizing strategy for oral squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) activation has been shown to play a critical role in tumor angiogenesis. In this study, we investigate the correlation between EGFR mutations and cadherin-5 (CDH5), which is an angiogenic factor, in lung cancer cells. Increased expression CDH5 is observed in lung cancer cells with EGFR mutations. Stable lung cancer cell lines expressing mutant (exon 19 deletion E746-A750, and exon 21 missense mutation L858R) and wild type EGFR genes are established. A significantly higher expression of CDH5 is observed in exon 19 deletion stable lung cancer cells and mouse xenografts. Further studies show that expression of CDH5 is decreased after the inhibition of EGFR and downstream Akt pathways in lung cancer cells with EGFR mutation. In addition, mutant EGFR genes potentiates angiogenesis in lung cancer cells, which is inhibited by CDH5 siRNA, and potentiates migration and invasion in lung cancer cells. Our study shows that mutant EGFR genes are associated with overexpression of CDH5 through increased phosphorylation of EGFR and downstream Akt pathways. Our result may provide an insight into the association of mutant EGFR and CDH5 expression in lung cancer and aid further development of target therapy for NSCLC in the future.

BackgroundThe worldwide elderly (≥ 65 years old) dialysis population has grown significantly. This population is expected to have more comorbid conditions and shorter life expectancies than the general elderly population. Predicting outcomes for this population is important for decision-making. Recently, a new comorbidity index (nCI) with good predictive value for patient outcomes was developed and validated in chronic dialysis patients regardless of age. Our study examined the nCI outcome predictability in elderly dialysis patients.Methods and findingsFor this population-based cohort study, we used Taiwan's National Health Insurance Research Database of enrolled elderly patients, who began maintenance dialysis between January 1999 and December 2005. A total of 21,043 incident dialysis patients were divided into 4 groups by nCI score (intervals ≤ 3, 4-6, 7-9, ≥ 10) and followed nearly for 10 years. All-cause mortality and life expectancy were analyzed. During the follow-up period, 11272 (53.55%) patients died. Kaplan-Meier curves showed significant group difference in survival (log-rank: PConclusionThe nCI, even without the age component, is a strong predictor of mortality in elderly dialysis patients. Because patients with lower nCI scores may predict better survival, more attention should paid to adequate dialysis rather than palliative care, especially in those without obvious functional impairments.

BACKGROUND: Dementia increases the risk of death in older patients hospitalized for acute illnesses. However, the effect of dementia on the risks of developing acute organ dysfunction and severe sepsis as well as on the risk of hospital mortality in hospitalized older patients remains unknown, especially when treatments for these life-threatening situations are considered. METHODS: In this population-based cohort study, we analyzed 41,672 older (≥ 65 years) patients, including 3,487 (8.4%) with dementia, from the first-time admission claim data between 2005 and 2007 for a nationally representative sample of one million beneficiaries enrolled in the Taiwan National Health Insurance Research Database. Outcomes included acute organ dysfunction, severe sepsis, and hospital mortality. The effect of dementia on outcomes was assessed using multivariable logistic regression. RESULTS: Dementia was associated with a 32% higher risk of acute organ dysfunction (adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.19-1.46), a 50% higher risk of severe sepsis (aOR 1.50, 95% CI 1.32-1.69) and a 28% higher risk of hospital mortality (aOR 1.28, 95% CI 1.10-1.48) after controlling age, sex, surgical condition, comorbidity, principal diagnosis, infection status, hospital level, and length of hospital stay. However, the significant adverse effect of dementia on hospital mortality disappeared when life-support treatments, including vasopressor use, hemodialysis, mechanical ventilation, and intensive care, were also controlled. CONCLUSIONS: In hospitalized older patients, the presence of dementia increased the risks of acute organ dysfunction, severe sepsis and hospital mortality. However, after intervention using life-support treatments, dementia only exhibited a minor role on short-term mortality.