Assessing the Prognostic Utility of the New Mayo Adhesive Probability Score in East Asian Populations and its Correlation with Metabolic-Associated Fatty Liver Disease.

We assessed the prognostic utility of the new perinephric fat adherence risk score - Mayo Adhesive Probability (MAP), in patients of East Asian ethnicity undergoing either laparoscopic partial nephrectomy (LPN) or laparoscopic radical nephrectomy (LRN). A retrospective analysis of clinical data was carried out on 169 patients who either underwent LPN or LRN surgery. These patients were categorized into two groups, group A (0-2 points) and group B (3-4 points) using the new MAP score. The overall clinical data between these two groups was compared and potential risk factors were investigated using logistic regression analyses. The new MAP score yielded an area under the curve of 0.761 (95 % CI: 0.691-0.831), indicating its effectiveness. Group B had a significantly higher incidence of adherent perirenal fat (APF) during surgery (p<0.001) and had a greater average age (p<0.001). There was an increased prevalence of hypertension (p=0.009), type 2 diabetes mellitus (p<0.001), and MAFLD (p<0.001) in group B. Additionally, there were significant differences in posterior perinephric fat thickness (p<0.05), lateral perinephric fat thickness (p<0.001), and perinephric stranding (p<0.001) between the two groups. The new MAP score holds significance in predicting APF in people of East Asian ethnicity undergoing LPN or LRN, and there is a strong correlation between elevated MAP scores and risk factors such as MAFLD and advanced age.

[Construction of TRAF6 ubiquitin site 331 mutant colorectal cancer cell stable line and its effect on biological behavior of colorectal cancer cells].

Objective: To investigate the effect of ubiquitin mutation at position 331 of tumor necrosis factor receptor related factor 6 (TRAF6) on the biological characteristics of colorectal cancer cells and its mechanism. Methods: lentivirus wild type (pCDH-3×FLAG-TRAF6) and mutation (pCDH-3×FLAG-TRAF6-331mut) of TRAF6 gene expression plasmid with green fluorescent protein tag were used to infect colorectal cancer cells SW480 and HCT116, respectively. The infection was observed by fluorescence microscope, and the expressions of TRAF6 and TRAF6-331mut in cells was detected by western blot. Cell counting kit-8 (CCK-8) and plate cloning test were used to detect the proliferation ability of colorectal cancer cells in TRAF6 group and TRAF6-331mut group, cell scratch test to detect cell migration, Transwell chamber test to detect cell migration and invasion, immunoprecipitation to detect the ubiquitination of TRAF6 and TRAF6-331mut with ubiquitinof lysine binding sites K48 and K63. Western blot was used to detect the effects of TRAF6 and TRAF6-331mut over expression on the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinase mitogen-activated protein kinase (MAPK)/activating protein-1(AP-1) signal pathway. Results: The successful infection of colorectal cancer cells was observed under fluorescence microscope. Western blot detection showed that TRAF6 and TRAF6-331mut were successfully expressed in colorectal cancer cells. The results of CCK-8 assay showed that on the fourth day, the absorbance values of HCT116 and SW480 cells in TRAF6-331mut group were 1.89±0.39 and 1.88±0.24 respectively, which were lower than those in TRAF6 group (2.09±0.12 and 2.17±0.45, P=0.036 and P=0.011, respectively). The results of plate colony formation assay showed that the number of clones of HCT116 and SW480 cells in TRAF6-331mut group was 120±14 and 85±14 respectively, which was lower than those in TRAF6 group (190±21 and 125±13, P=0.001 and P=0.002, respectively). The results of cell scratch test showed that after 48 hours, the percentage of wound healing distance of HCT116 and SW480 cells in TRAF6-331mut group was (31±12)% and (33±14)%, respectively, which was lower than those in TRAF6 group [(43±13)% and (43±7)%, P=0.005 and 0.009, respectively]. The results of Transwell migration assay showed that the migration numbers of HCT116 and SW480 cells in TRAF6-331mut group were significantly lower than those in TRAF6 group (P<0.001 and P<0.002, respectively). The results of Transwell invasion assay showed that the number of membrane penetration of HCT116 and SW480 cells in TRAF6-331mut group was significantly lower than those in TRAF6 group (P=0.008 and P=0.009, respectively). The results of immunoprecipitation detection showed that the ubiquitin protein of K48 chain pulled by TRAF6-331mut was lower than that of wild type TRAF6 in 293T cells co-transfected with K48 (0.57±0.19), and the ubiquitin protein of K63 chain pulled down by TRAF6-331mut in 293T cells co-transfected with K63 was lower than that of wild type TRAF6 (0.89±0.08, P<0.001). Western blot assay showed that the protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-HCT116 cells were 0.63±0.08, 0.42±0.08 and 0.60±0.07 respectively, which were lower than those in TRAF6-HCT116 cells (P=0.002, P<0.001 and P<0.001, respectively). The expression level of AP-1 protein in TRAF6-HCT116 cells was 0.89±0.06, compared with that in TRAF6-HCT116 cells. The difference was not statistically significant (P>0.05). The protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-SW480 cells were 0.50±0.06, 0.51±0.04, 0.48±0.02, respectively, which were lower than those in TRAF6-SW480 cells (all P<0.001). There was no significant difference in AP-1 protein expression between TRAF6-331mut-SW480 cells and TRAF6-SW480 cells. Conclusion: The ubiquitin site mutation of TRAF6 gene at 331 may prevent the binding of TRAF6 and ubiquitin lysine sites K48 and K63, and then affect the expressions of proteins related to downstream NF-κB and MAPK/AP-1 signal pathways, and inhibit the proliferation, migration and invasion of colorectal cancer cells.

Quality validation of platelets obtained from the Haemonetics and Trima Accel automated blood-collection systems.

BACKGROUND: Platelet transfusion is required to treat haemo-oncology or trauma patients. Platelet apheresis (PA) performed with apheresis equipment has increased rapidly in recent years. Leucocyte-reduced platelet apheresis (LRPA) can reduce the risk of platelet refractoriness and febrile nonhemolytic transfusion reactions (FNHTRs) for transfusion. Accordingly, this study aimed to investigate and compare the platelet metabolic and functional responses between PA performed with Haemonetics and LRPA performed with Trima Accel cell separator. METHODS: The qualities of platelets collected through PA and LRPA were evaluated in terms of visual appearance, morphology, platelet-aggregation changes, metabolic activities, and bacterium-screening test during 5-day storage. Statistical analyses included two-sample t-test and generalised estimating equation(GEE) method. RESULTS: During 5-day storage in LRPA, residual leucocytes were all <1.0×106, and the parameters of platelet function were as follows: platelet aggregated to agonists such as adenosine 5'-diphosphate (ADP) and collagen, and the extent of shape change and pO2 showed no statistically significant difference between PA and LRPA. The hypotonic shock reaction (HSR) on days 0, 1, and 3 were significantly higher in LRPA than in PA (71.78±6.92 vs. 64.10±7.42; P=0.002; 71.53±8.98 vs. 62.96±9.84; P=0.007; 68.05±7.28 vs. 57.76±6.80; P<0.0001, respectively). Values of mean platelet volume (MPV) were statistically larger in PA than in LRPA on days 0, 1, and 3. On day 5, the swirling score was higher in LRPA than in PA. The mean lactate levels had no statistically significant difference between PA and LRPA. Moreover, no growth was observed through bacterium-screening test conducted on 40 samples. CONCLUSION: Comparison of LRPA and PA products collected from the Trima Accel and Haemonetics automated blood-collection systems, respectively, revealed that both products possessed good platelet qualities even though additional processes are needed to reduce leucocytes. Furthermore, investigating the outcomes of other apheresis instruments with focus on the safety of donors, products, and recipients is necessary.

Insulin enhances and metformin reduces risk of colorectal carcinoma in type-2 diabetes.

BACKGROUND: Identifying colorectal cancer associated risks is important for conducting a program for the survey and prevention of colorectal cancer. AIM: To investigate the association between use of insulin or metformin with colorectal cancer (CRC) in type 2 diabetes (T2DM). DESIGN: Population-based cohort study. METHODS: Through analysis of National Health Insurance (NHI) database between 1998 and 2010 in Taiwan, we identified 66 324 T2DM patients aged ≥ 20 years and selected subjects without diabetes by 1: 1 randomly matching with the study cohort based on age, sex and index date. We followed up the participants until 31 December 2011 or when they withdrew from the NHI program. RESULTS: Compared with non-diabetic subjects, the T2DM patients exhibited an increased risk of CRC [adjusted HR (aHR) = 1.56, 95% confidence interval (CI) = 1.39-1.75], after adjustment for age, sex, urbanization level, comorbidities and examinations of colonoscopy, sigmoidoscopy, or stool occult blood test. Among the T2DM patients, insulin usage increased the risk of CRC (aHR = 1.86, 95% CI = 1.58-0-2.19) after adjustment for age, sex, urbanization level, comorbidities, metformin usage and examinations; nevertheless, metformin decreased the risk of CRC (aHR = 0.65, 95% CI = 0.54-0.77) after adjustment for age, sex, urbanization level, comorbidities, insulin usage and examinations. Compared with the non-insulin cohort, the risk of CRC tended to increase with the incremental dosage of insulin exposure. CONCLUSION: Our population-based cohort study demonstrated an association between T2DM and CRC. Among the T2DM patients, insulin use was associated with an increased risk of CRC and metformin use was associated with a decreased risk of CRC. Inability to obtain information on several potential confounding factors, such as lifestyle and dietary habits, is the major limitation of the study.

Tunability of Acoustic and Mechanical Behaviors in Breast Tissue Mimicking Materials.

In radiology practices, the ultrasound-guided breast biopsy is among the most commonly performed minimally invasive procedures. However, many radiology residents in their graduate residencies are found with little or no hands-on experience with ultrasound-guided breast procedures. To enhance safety, the problem can be solved by the use of anthropomorphic training phantoms which can provide the resident with realistic ultrasound imaging and needle insertion haptic feedback. Stiffness and acoustic properties of breast tissues vary between different people. The training breast phantom should be able to possess different acoustic and mechanical properties which conform the inconsistencies found in real tissues among people. Therefore, this paper investigates the tunability of acoustic and mechanical behaviors in breast tissue mimicking materials (TMMs). Experiments of central composite design (CCD) with a center point, four corner points, and an additional four axis points were used to fit the non-linear regression model of the speed of sound. The same design of experiment approach was then used to fit the second-order response surface of the attenuation coefficient. Suitable series of tissue mimicking materials for the glandular tissue and malignant lesion were suggested. Latin hypercube design method was conducted to evaluate the main factors that affected the mechanical property (Young's modulus) of tissue mimicking materials. The results showed that the recipe of tissue mimicking materials could be customized to possess different acoustic and mechanical properties which conform the inconsistencies found in real breast tissues.

GPIIb/IIIa expression changes in atrial fibrillation post radiofrequency ablation.

OBJECTIVE: Atrial fibrillation (AF) is one of the most common arrhythmias affecting the patient's quality of life, and its complications of thromboembolism can lead to serious consequences. AF patients are often in hypercoagulation status that can affect the prognosis. GPIIb/IIIa is a fibrinogen receptor that can bind to the ligands of platelet and cause aggregation. Therefore, GPIIb/IIIa can be treated as a marker of hemagglutination. This work aims to analyze the changes of GPIIb/IIIa after radiofrequency ablation of atrial fibrillation, and to investigate its relationship with recurrence. PATIENTS AND METHODS: A total of AF 80 patients in our hospital received radiofrequency ablation from January 2017 to August 2017. Peripheral blood was collected 1 week after surgery. A total of 40 healthy volunteers were enrolled as control group. GPIIb/IIIa was analyzed by enzyme-linked immunosorbent assay (ELISA). High-sensitivity troponin (hs-cTnT), fasting plasma glucose (FPG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglyceride levels (TG) were analyzed by using electrochemical luminescence assay. Body mass index (BMI), smoking index, and age were recorded. RESULTS: Compared with the non-recurrence group, GPIIb/IIIa, hs-cTnT, FPG, LDL, TC, and TG levels increased, whereas HDL level declined in the recurrence group (p < 0.05). There was a positive correlation between GPIIb/IIIa and hs-cTnT, FPG, LDL, TC, TG, BMI, and smoking index, and a negative correlation with HDL (p < 0.05). GPIIb/IIIa was positively correlated with postoperative recurrence (p < 0.05). CONCLUSIONS: Increased GPIIb/IIIa expression after radiofrequency ablation of AF is associated with myocardial injury, suggesting a risk of postoperative recurrence.

Review article: the prevention of hepatitis B-related hepatocellular carcinoma.

BACKGROUND: Ample evidence indicates an aetiological association of persistent hepatitis B virus (HBV) infection with hepatocellular carcinoma (HCC). Several viral, host and external risk factors for the development of HBV-related HCC have been documented. AIMS: To summarise and discuss the risk stratification and the preventive strategies of HBV-related HCC. METHODS: Recent published studies identified from PubMed were comprehensively reviewed. The key words included chronic hepatitis B, HBV, hepatocellular carcinoma, prevention and antiviral therapy. RESULTS: The incidence of HCC is extremely high in HBV hyperendemic areas. For HBV patients left untreated, significant risk factors for HCC include male gender, aging, advanced hepatic fibrosis, persistent serum transaminase elevation, specific HBV entry receptor (NTCP) genotype, PM2.5 exposure, HBeAg positivity, HBV genotype C/D/F, high proportion of core promoter mutation, pre-S deletion, high serum levels of HBV DNA and HBsAg as well as co-infection with HCV, HDV and HIV. Primary prevention of HBV-related HCC can be achieved through universal HBV vaccination and anti-viral prophylaxis for high viraemic mothers. The goal of secondary prevention has been reached by effective anti-viral therapy to reduce the risk of HCC development in chronic hepatitis B patients. However, whether HCC is prevented or delayed deserves further examination. Finally, several studies confirmed the tertiary preventive effect of anti-viral therapy in reducing risk of HCC recurrence after curative therapies. CONCLUSIONS: Through the strategies of three-level prevention, the global burden of HBV-related HCC should decline over time and even be eliminated in conjunction with HBV cure.

Risk of age-related macular degeneration in patients with prostate cancer: a nationwide, population-based cohort study.

BACKGROUND: Prostate cancer (PC) can be related to increased systemic oxidative stress and dihydrotestosterone level, which are also reported to be involved in the pathogenesis of age-related macular degeneration (AMD). We conducted a cohort study to determine whether patients with PC have an increased risk of AMD. PATIENTS AND METHODS: Data were collected from the Taiwan Longitudinal Health Insurance Database for the 1999-2010 period. The study PC cohort comprised 22 084 patients aged ≥18 years with a first diagnosis of PC. The comparison cohort consisted of age-, occupation-, and urbanization level-matched patients at a ratio of 1 : 1. The primary outcome was the incidence of AMD, which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling. RESULTS: The mean follow-up periods (standard deviation) for the patients with AMD in the age-, occupation-, and urbanization level-matched PC cohort and non-PC cohorts were 4.69 (2.90) and 5.51 (2.82) years. The mean age of the PC cohort was 73.9 years and that of the non-PC cohort was 73.2 years, with approximately 85.9% of the patients aged >65 years. The PC cohort had a higher risk of AMD than did the propensity score-matched non-PC cohort with an adjusted hazard ratio of 1.25 (95% confidence interval, 1.12-1.39). Compared with PC cohort receiving no injection hormone therapy, the PC cohort receiving injection hormone therapy had a lower risk of AMD (adjusted hazard ratio, 0.56; 95% confidence interval, 0.41-0.76). CONCLUSION: PC is associated with an increased risk of AMD. Patients with PC receiving injected form of androgen deprivation therapy had a lower risk of AMD than patients with PC not receiving injected form of androgen-deprivation therapy.

The protective role of nitric oxide-dependent innate immunosuppression in the early stage of cartilage damage in rats: Role of nitric oxide in cartilage damage.

OBJECTIVES: Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the human population. Recently, increased concentration of nitric oxide in serum and synovial fluid in patients with OA has been observed. However, the exact role of nitric oxide in the initiation of OA has not been elucidated. The aim of the present study was to investigate the role of nitric oxide in innate immune regulation during OA initiation in rats. METHODS: Rat OA was induced by performing meniscectomy surgery while cartilage samples were collected 0, 7, and 14 days after surgery. Cartilage cytokine levels were determined by using enzyme-linked immunosorbent assay, while other proteins were assessed by using Western blot RESULTS: In the time course of the study, nitric oxide was increased seven and 14 days after OA induction. Pro-inflammatory cytokines including tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 were decreased. L-NG-Nitroarginine methyl ester (L-NAME, a non-specific nitric oxide synthase inhibitor) significantly decreased cartilage nitric oxide and blocked immune suppression. Further, L-NAME decreased Matrix metalloproteinase (MMPs) and increased tissue inhibitor of metalloproteinase (TIMP) expression in meniscectomised rats. CONCLUSION: Nitric oxide-dependent innate immune suppression protects cartilage from damage in the early stages of OA initiation in rats.Cite this article: C-C. Hsu, C-L. Lin, I-M. Jou, P-H. Wang, J-S. Lee. The protective role of nitric oxide-dependent innate immunosuppression in the early stage of cartilage damage in rats: Role of nitric oxide in ca rtilage da mage. Bone Joint Res 2017;6:253-258. DOI: 10.1302/2046-3758.64.BJJ-2016-0161.R1.

Risk of empyema in patients with end-stage renal disease: a nationwide propensity-matched cohort study.

BACKGROUND: Empyema is a rare but important complication among patients with end-stage renal disease (ESRD). However, a nationwide, propensity-matched cohort study has never been performed. METHODS: We conducted a retrospective cohort study using data from the National Health Insurance Research Database of Taiwan. The ESRD group consisted of 82 765 patients diagnosed between 2000 and 2008. The comparison group consisted of individuals without kidney disease selected at a 1:1 ratio matched by propensity score estimated with age, gender, year of diagnosis and comorbidities. The occurrence of empyema was monitored until the end of 2011. The hazard ratios (HRs) of empyema were estimated using the Cox proportional hazards model. RESULTS: The incidence of empyema was 2.76-fold higher in the ESRD group than in the comparison group (23.7 vs. 8.19/10 000 person-years, P <0.001), with an adjusted HR of 3.01 [95% confidence interval (CI) = 2.67-3.39]. There was no difference of the incidence of empyema between hemodialysis (HD) and peritoneal dialysis (PD) (adjusted HR = 0.96, 95% CI = 0.75-1.23). In addition, 30-day mortality rate since empyema diagnosis was significantly higher in ESRD group than the comparison group (15.9% vs. 10.9%), with an adjusted OR of 1.69 (95% CI = 1.17-2.44). CONCLUSION: The risk of empyema was significantly higher in patients with ESRD than in those without kidney disease. The occurrence of empyema was without difference in patients undergoing HD compared to those undergoing PD. The 30-day mortality rate since empyema diagnosis was also significantly higher in patients with ESRD.

Review article: novel therapies for hepatitis B virus cure - advances and perspectives.

BACKGROUND: Current anti-viral therapies, interferon and nucleos(t)ide analogues, have been proven to reduce the progression of chronic hepatitis B (CHB). However, covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) persists, resulting in viral relapse after the discontinuation of treatment. AIM: To discuss and review novel therapies for chronic hepatitis B infection. METHODS: Recent published studies which searched from PubMed were comprehensive reviewed. The key words include chronic hepatitis B, hepatitis B virus cure, covalently closed circular DNA, direct acting anti-virals and host targeting agents. RESULTS: Several novel agents through viral and host targets approaches are under investigations towards functional cure of HBV. On the one hand, direct acting anti-virals targeting virus itself, such as HBV new polymerase inhibitor, entry inhibitor, engineered site-specific nucleases and RNA interference, could inhibit amplification of cccDNA as well as intrahepatic HBV infection and eliminate or silence cccDNA transcription. Inhibitors of HBV nucleocapsid assembly suppress capsid formation and prevent synthesis of HBV DNA. On the other hand, host targeting agents (HTA) include lymphotoxin-ß receptor agonist, toll-like receptor agonist, immune checkpoint inhibitors and adenovirus-based therapeutic vaccine. Through enhancing innate and adaptive immune responses, these agents could induce noncytolytic destruction of cccDNA or attack HBV-infected hepatocytes. CONCLUSION: With these promising approaches, we hope to reach global hepatitis B virus control in the middle of this century.

Unprovoked venous thromboembolism and subsequent cancer risk: a population-based cohort study.

UNLABELLED: ESSENTIALS: A relationship between unprovoked venous thromboembolism (VTE) and cancer risk was investigated. We collected 27,751 VTE patients and compared them with 110,409 frequency-matched people without VTE. This cohort study showed significantly higher risks of overall and site-specific cancers in the VTE group. There is an increased risk in the first 6 months after VTE, and VTE can be an indicator of occult cancer. BACKGROUND: We investigated the relationship between unprovoked venous thromboembolism (VTE) and subsequent cancer risk in Taiwan, focusing on both short-term and long-term cancer development. METHODS: For the case group, we obtained data on 27,751 patients diagnosed with unprovoked VTE between 1 January 1998, and 31 December 2008. For the comparison group, four people without unprovoked VTE were frequency-matched with each unprovoked VTE patient according to age, sex, and index year. Cox proportional hazards regression models were employed to determine the effects of unprovoked VTE on cancer risk. RESULTS: Overall cancer risk was significantly higher in the unprovoked VTE group than in the comparison group (adjusted hazard ratio = 2.26, 95% confidence interval = 2.16-2.37). The increased risk was observed in both men and women in various age groups. The patients in the unprovoked VTE group showed a significantly increased risk of cancer at all site-specific cancer sites. Analyses stratified according to follow-up duration revealed that significant differences were more evident between the two groups over a follow-up duration of < 0.5 years than over a follow-up duration of ≥ 3 years. Furthermore, the 1-year mortality risk of cancer patients with unprovoked VTE was significantly higher than that for cancer patients in the non-VTE group. CONCLUSION: The results of this study show that unprovoked VTE is associated with a consistently high risk of subsequent cancer diagnosis. This is particularly true in the first 6 months after VTE. It suggests that unprovoked VTE can be an indicator of occult malignancy.

Increased risk of lung cancer among patients with bronchiectasis: a nationwide cohort study.

BACKGROUND: We conducted a longitudinal nationwide cohort study in Taiwan to determine whether patients with bronchiectasis are at an increased risk of developing lung cancer. METHODS: This study investigated the incidence and risk for lung cancer in 57 576 patients newly hospitalized with bronchiectasis between 1998 and 2010 from the Taiwan National Health Insurance Research Database. The comparison cohort comprised 230 304 individuals from the general population without bronchiectasis. The follow-up period was from the time of the initial hospitalization for bronchiectasis to the date of a lung cancer diagnosis, censoring, or 31 December 2011. We used Cox proportional hazard regression models to analyse the risk of lung cancer by including the variables of sex, age and comorbidities. RESULTS: The incidence of lung cancer was higher in patients with bronchiectasis than in the comparison cohort (4.58 vs. 2.02 per 1000 person-years). The bronchiectasis patients exhibited a 2.36-fold increased risk of lung cancer compared with the comparison cohort after adjustment for age, sex and comorbidities (adjusted hazard ratio [aHR] = 2.36, 95% confidence interval [CI] = 2.19-2.55). The sex-specific bronchiectasis cohort to comparison cohort revealed that the aHR was 2.41 (95% CI = 2.11-2.76) for the women and 2.33 (95% CI = 2.12-2.56) for the men. The incidence rate of lung cancer increased as age increased in both cohorts. CONCLUSION: This nationwide study determined that the patients with bronchiectasis exhibited an increased risk of lung cancer compared with the general population.

Unresolved issues in the analysis of F2-isoprostanes, F4-neuroprostanes, isofurans, neurofurans, and F2-dihomo-isoprostanes in body fluids and tissue using gas chromatography/negative-ion chemical-ionization mass spectrometry.

F2-isoprostanes (F2-IsoPs) generated from arachidonic acid (AA) have been recognized as the most reliable marker of nonenzymatic lipid peroxidation in vivo. F2-IsoPs are initially produced in esterified form on phospholipids, and then released into body fluids in free form. The same mechanism can lead to generation of F4-neuroprostanes (F4-NPs) and F2-dihomo-IsoPs from docosahexaenoic acid (DHA) and adrenic acid, respectively. In addition, isofurans (IsoFs) and neurofurans (NFs) may be preferentially produced from AA and DHA, respectively, under high oxygen tension. The detection of F2-IsoPs using gas chromatography/negative-ion chemical-ionization mass spectrometry (GC/NICI-MS) has been widely employed, which is important for human body fluids containing low quantity of free-form F2-IsoPs. F4-NPs have also been detected using GC/NICI-MS, but multiple peaks need to be quantified. In this paper, we summarize the basic workflow of the GC/NICI-MS method for analyzing F2-IsoPs and F4-NPs, and various formats of assays conducted by different groups. We then discuss the feasibility of simultaneous analysis of IsoFs, NFs, and F2-dihomo-IsoPs with F2-IsoPs or F4-NPs. Representative GC chromatograms for analyzing these markers in human body fluids and rat brain tissue are demonstrated. Furthermore, we discuss several factors that may affect the performance of the analysis, such as those related to the sample processing steps, interference from specimens, types of GC liners used, and the addition of electron multiplier voltage in the method setting for the MS detector. Finally, we question the appropriateness of measuring total (free plus esterified) levels of these markers in body fluids.

5α-Reductase inhibitors increase acute coronary syndrome risk in patients with benign prostate hyperplasia.

BACKGROUND: This study explored the possible association between the use of two typical 5ARIs (finasteride and dutasteride) and the risk of acute coronary syndrome (ACS) in patients with benign prostate hyperplasia (BPH). METHODS: From the claims data of the Taiwan National Health Insurance (NHI) Taiwan, we identified 1843 ACS cases among BPH patients and randomly selected 7330 controls without ACS, with a similar mean age of 73 years. Multivariate logistic regression analysis estimated the odds ratio (OR) and 95 % confidence interval (CI) for the relationship between the 5ARIs medications and ACS risk. RESULTS: We found that BPH patients who had received treatment with both finasteride and dutasteride were at a higher risk of ACS with an OR of 3.47 (95 % CI 1.05-11.5), compared to patients without 5ARIs treatment. Furthermore, the dosage analysis showed that there were no significant associations between ACS risk and uses of a single drug medication regardless the dosages. The ORs for those who took only dutasteride were 1.07 (95 % CI 0.39-2.99) with low dose and 0.73 (95 % CI 0.38-1.44) with high dose. The ORs for those who took only finasteride were 1.30 (95 % CI 0.89-1.92) with low dose and 0.98 (95 % CI 0.19-5.13) with high dose. CONCLUSION: This population-based nested case-control study suggests that 5ARI use may increase ACS risk among patients with BPH when patients were exposed to both finasteride and dutasteride.

Association between lumbar discectomy and subsequent cervical discectomy.

BACKGROUND: Lumbar discectomy (LD) is one of the most common spinal surgical procedures. However, the remote effect of the cervical spine has seldom been discussed. The comparative incidence of cervical discectomy with or without a previous LD is an essential feature in predicting this effect. METHODS: A cohort comparative study was conducted from the National Health Research Institute, Taiwan, over the period from 1996 to 2010. Patients who received LDs and patients who did not receive LDs in the same period were randomly selected to serve as samples for comparison. A total of 14 480 patients who did not undergo LD surgery and 3620 patients who received LDs were enrolled in this study. The incidence rates of discectomy-cervical in both groups were calculated from the follow-up period until the end of 2010. The baseline comorbidity history was determined for each patient. Comorbidities included facture and osteoporosis. RESULTS: During the follow-up period, the overall incidence rate of CD was significantly higher in patients who were treated with LD than in those who were not (24.7 vs. 2.73 per 10 000 person years). The risk of CD in the LD-treated cohort was ∼9-fold greater than that of the non-LD-treated cohort (HRs = 8.58, 95% CI = 5.38-13.7). CONCLUSION: Patients who have undergone LDs are at A greater risk of subsequent CDs, an increased risk that is evident in all patients regardless of demographics or the presence of fracture or osteoporosis.

Survival outcome of patients with nasopharyngeal carcinoma: a nationwide analysis of 13 407 patients in Taiwan.

OBJECTIVES: We reported the contemporary survival outcome of patients with nasopharyngeal carcinoma (NPC) and analysed the factors affecting survival. DESIGN: A retrospective cohort study. SETTING: A nationwide population-based study in Taiwan. PARTICIPANTS: We identified 13 407 patients with newly diagnosed NPC from 2002 to 2010. MATERIAL AND METHODS: The multivariate Cox proportional hazards model was performed to measure the mortality-association risk factor in patients with NPC after adjusting for NPC treatment and socio-demographic characteristics. RESULTS: The 1-, 2-, 5- and 8-year overall survival (OS) rates were 89.6%, 80.4%, 65.2% and 56.5%, respectively. The factors associated with mortality risk were sex (men versus women, HR = 1.45), age (>60 versus ≤ 40 years, HR = 3.61), geographic region of residence (eastern Taiwan versus northern Taiwan HR = 1.39), income (<15 840 versus >25 000, HR = 1.87) and treatment modality (chemotherapy alone versus radiotherapy alone, HR = 2.25). CONCLUSION: The contemporary 5-year OS rate was 65.2% in Taiwan. Male patients, old age, residing in eastern Taiwan, low income and receiving chemotherapy alone were independent predictors for poor OS.

Helicobacter pylori infection and the risk of acute coronary syndrome: a nationwide retrospective cohort study.

Helicobacter pylori infection (HPI) imposes substantial social costs and is of major etiological importance in peptic ulcer disease, gastric cancer, and accelerated cardiovascular diseases. This study determined the risk of acute coronary syndrome (ACS) associated with HPI in a nationwide retrospective cohort study. By using the Taiwan National Health Insurance Research Database (NHIRD), we identified patients diagnosed with HPI from 1998 to 2010. In addition, we randomly selected non-HPI controls frequency-matched by age, sex, and index year from the general population free of HPI. The risk of ACS was analyzed using Cox proportional hazards regression models in which sex, age, and comorbidities were included as variables. We identified 17,075 participants for the HPI group and selected 68,300 participants for the comparison group. The incidence rates were increased in the patients in the HPI group compared with those in the comparison group. Overall, the HPI patients exhibited a 1.93-fold high crude hazard ratio for ACS, and a 1.48-fold adjusted hazard ratio after age, sex, and comorbidities were adjusted. However, the overall adjusted hazard ratio of ACS increased with increasing age with a 3.11 to 8.24 adjusted hazard ratio among the various age groups. Several comorbidities, such as diabetes, hyperlipidemia, and COPD exhibited synergistic effects for ACS risk. We determined a significant association between ACS and comorbidities and provide evidence to encourage clinicians to observe ACS-related comorbidities.