Improved risk stratification of nasopharyngeal cancer by targeted sequencing of Epstein-Barr virus DNA in post-treatment plasma.

BACKGROUND: Quantitative measurement of plasma Epstein-Barr virus (EBV) DNA by real-time PCR at the end of primary treatment is a robust prognostic marker for nasopharyngeal carcinoma (NPC) patients. However, up to 40% of patients who would later develop disease recurrence had undetectable post-treatment plasma EBV DNA. Targeted sequencing for the entire EBV genome potentially allows a more comprehensive and unbiased detection of plasma EBV DNA and enables the use of other parameters such as fragment size as biomarkers. Hence, we explored if plasma EBV DNA sequencing might allow more accurate prognostication of NPC patients. PATIENTS AND METHODS: Plasma samples collected from 769 patients with stage IIB-IVB NPC at 6-8 weeks after radiotherapy were analysed using targeted sequencing for EBV DNA. RESULTS: The sensitivities of the PCR-based analysis, at a cut-off of any detectable levels of plasma EBV DNA, for prediction of local and distant recurrences were 42.3% and 85.3%, respectively. The sequencing-based analysis (involving quantitation and size profiling) achieved better performance for both local and distant recurrences than PCR. Using a cut-off of the proportion of plasma EBV DNA deduced by sequencing at 0.01%, the sensitivities of the sequencing-based analysis for local and distant recurrences were 88.5% and 97.1%, with the resultant negative predictive values of 99.1% and 99.4%, respectively. Among patients with undetectable EBV DNA on quantitative PCR, sequencing could further define a subgroup that enjoyed superior survival outcomes based on the proportion of plasma EBV DNA, with a 5-year progression-free survival (PFS) approaching 90%. On multivariate analysis, sequencing-based quantitative level of plasma EBV DNA was the independent prognostic factor with the highest hazard ratio for prediction of overall survival and PFS. CONCLUSION: NPC prognostication using post-treatment plasma EBV DNA could be enhanced through sequencing.

One-year outcomes of an osteoporosis liaison services program initiated within a healthcare system.

Due to the huge gap in the care of patients with osteoporosis and fragility fractures, we aimed to explore the effectiveness of the osteoporosis liaison service (OLS) in osteoporosis care. We found that OLS can improve osteoporosis care, including increasing medication compliance, increasing calcium/vitamin D/protein intake, and reducing fall rate. INTRODUCTION: A significant gap exists in the care of patients with osteoporosis and fragility fractures. This study aimed to evaluate 1-year outcomes of an osteoporosis liaison service (OLS) program that includes two independent components: medication management services (MMS) to improve medication adherence and fracture liaison services (FLS) for secondary prevention. METHODS: Patients with new hip fracture or untreated vertebral fractures enrolled in the FLS program (n = 600), and those with osteoporosis medication management issues but not necessarily fragility fractures enrolled in the MMS program (n = 499) were included. To evaluate outcomes, care coordinators assessed baseline items adapted from the 13 Best Practices Framework (BPF) standards of the International Osteoporosis Foundation, with telephone follow-up every 4 months for 1 year. RESULTS: Mean age of this cohort was 76.2 ± 10.3 years, 78.8% were female. After 1-year participation in the program, all patients had received bone mineral density tests, and medication adherence for the entire cohort at 12 months was 91.9 ± 19.6%, with significant improvement in fall rates (23.4% reduction), exercise rates (16.8% increase), calcium intake (26.5% increase), vitamin D intake (26.4% increase), and adequate protein intake (17.3% increase) (all p < 0.05). After 1-year OLS program, the overall rates of mortality, incident fracture, and falls were 6.6%, 4.0%, and 24.3%, respectively. CONCLUSIONS: The OLS program is associated with improved osteoporosis care, including increased medication adherence, calcium/vitamin D and protein intake, and reduced fall rate.

Development of the Asia Pacific Consortium on Osteoporosis (APCO) Framework: clinical standards of care for the screening, diagnosis, and management of osteoporosis in the Asia-Pacific region.

Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. PURPOSE: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. METHODS: We conducted a structured comparative analysis of existing CPGs in the AP region using a "5IQ" model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. RESULTS: Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. CONCLUSION: The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.

Chronic kidney disease-related osteoporosis is associated with incident frailty among patients with diabetic kidney disease: a propensity score-matched cohort study.

Chronic kidney disease (CKD)-related osteoporosis is a major complication in patients with CKD, conferring a higher risk of adverse outcomes. We found that among those with diabetic kidney disease, this complication increased the risk of incident frailty, an important mediator of adverse outcomes. INTRODUCTION: Renal osteodystrophy and chronic kidney disease (CKD)-related osteoporosis increases complications for patients with diabetic kidney disease (DKD). Since musculoskeletal degeneration is central to frailty development, we investigated the relationship between baseline osteoporosis and the subsequent frailty risk in patients with DKD. METHODS: From the Longitudinal Cohort of Diabetes Patients in Taiwan (n = 840,000), we identified 12,027 patients having DKD with osteoporosis and 24,054 propensity score-matched controls having DKD but without osteoporosis. The primary endpoint was incident frailty on the basis of a modified FRAIL scale. Patients were prospectively followed-up until the development of endpoints or the end of this study. The Kaplan-Meier technique and Cox proportional hazard regression were used to analyze the association between osteoporosis at baseline and incident frailty in these patients. RESULTS: The mean age of the DKD patients was 67.2 years, with 55.4% female and a 12.6% prevalence of osteoporosis at baseline. After 3.5 ± 2.2 years of follow up, the incidence rate of frailty in patients having DKD with osteoporosis was higher than that in DKD patients without (6.6 vs. 5.7 per 1000 patient-year, p = 0.04). A Cox proportional hazard regression showed that after accounting for age, gender, obesity, comorbidities, and medications, patients having DKD with osteoporosis had a significantly higher risk of developing frailty (hazard ratio, 1.19; 95% confidence interval, 1.02-1.38) than those without osteoporosis. CONCLUSIONS: CKD-related osteoporosis is associated with a higher risk of incident frailty in patients with DKD.

Secondary prevention of fragility fractures in Asia Pacific: an educational initiative.

The Asia -Pacific Bone Academy (APBA) Fracture Liaison Service (FLS) Focus Group educational initiative has stimulated activity across the Asia -Pacific region with the intention of supporting widespread implementation of new FLS. In 2017, the APBA FLS Focus Group developed a suite of tools to support implementation of FLS across the Asia-Pacific region as a component of a multi-faceted educational initiative. This article puts this initiative into context with a narrative review describing the burden of fragility fractures in the region, the current secondary fracture prevention care gap and a summary of emerging best practice. The results of a survey to evaluate the impact of the APBA educational initiative is presented, in addition to commentary on recent activities intended to improve the care of individuals who sustain fragility fractures across the Asia -Pacific. A FLS Toolbox for Asia-Pacific was developed which included the following sections:1. The burden of fragility fractures in the Asia-Pacific region.2. A summary of evidence for FLS in the Asia-Pacific.3. A generic, fully referenced FLS business plan template.4. Potential cost savings accrued by each country, based on a country-specific FLS Benefits Calculator.5. How to start and expand FLS programmes in the Asia-Pacific context.6. A step-by-step guide to setting up FLS in countries in the Asia-Pacific region.7. Other practical tools to support FLS establishment.8. FLS online resources and publications.The FLS Toolbox was provided as a resource to support FLS workshops immediately following the 5th Scientific Meeting of the Asian Federation of Osteoporosis Societies (AFOS) held in Kuala Lumpur in October 2017. The FLS workshops addressed three key themes:• The FLS business case.• Planning the FLS patient pathway.• The role of the FLS coordinator in fragility fracture care management.A follow-up survey of 142 FLS workshop participants was conducted in August-September 2018. The survey included questions regarding how FLS were developed, funded, the scope of service provision and the support provided by the educational initiative. Almost one-third (30.3%) of FLS workshop participants completed the survey. Survey responses were reported for those who had established a FLS at the time the survey was conducted and, separately, for those who had not established a FLS. Findings for those who had established a FLS included:• 78.3% of respondents established a multidisciplinary team to develop the business case for their FLS.• 87.0% of respondents stated that a multidisciplinary team was established to design the patient pathway for their FLS.• 26.1% of respondents stated that their FLS has sustainable funding.• The primary source of funding for FLS was from public hospitals (83.3%) as compared with private hospitals (16.7%).Most hospitals that had not established a FLS at the time the survey was conducted were either in the process of setting-up a FLS (47%) or had plans in place to establish a FLS for which approval is being sought (29%). The primary barrier to establishing a new FLS was lack of sustainable funding. The APBA FLS Focus Group educational initiative has stimulated activity across the Asia-Pacific region with the intention of supporting widespread implementation of new FLS. A second edition of the FLS Toolbox is in development which is intended to complement ongoing efforts throughout the region to expedite widespread implementation of FLS.

Identifying characteristics of an effective fracture liaison service: systematic literature review.

Fracture liaison services (FLS) have been demonstrated to improve outcomes following osteoporotic fracture. The aim of this systematic literature review (SLR) was to determine the characteristics of an FLS that lead to improved patient outcomes. We conducted a SLR, including articles published between 2000 and February 2017, using global (Medline, EMBASE, PubMed and Cochrane Library) and local databases. Studies including patients aged ≥ 50 years with osteoporotic fractures enrolled in an FLS were assessed. Information extracted from each article included key person coordinating the FLS (physician, nurse or other healthcare professional), setting (hospital vs community), intensity (single vs multiple), duration (long vs short term), fracture type and gender. A meta-analysis of randomised controlled trials was conducted based on the key person coordinating the FLS. Out of 7236 articles, 57 were considered to be high quality and identified for further analysis. The SLR identified several components which contributed to FLS success, including multidisciplinary involvement, driven by a dedicated case manager, regular assessment and follow-up, multifaceted interventions and patient education. Meta-analytic data confirm the effectiveness of an FLS following an osteoporotic fracture: approximate 27% increase in the likelihood of BMD testing and up to 21% increase in the likelihood of treatment initiation compared with usual care. The balance of evidence indicates that the multifaceted FLS and dedicated coordination are important success factors that contribute to effective FLS interventions which reduce fracture-related morbidity and mortality.

Nutrition and physical activity in the prevention and treatment of sarcopenia: systematic review.

This systematic review summarizes the effect of combined exercise and nutrition intervention on muscle mass and muscle function. A total of 37 RCTs were identified. Results indicate that physical exercise has a positive impact on muscle mass and muscle function in subjects aged 65 years and older. However, any interactive effect of dietary supplementation appears to be limited. INTRODUCTION: In 2013, Denison et al. conducted a systematic review including 17 randomized controlled trials (RCTs) to explore the effect of combined exercise and nutrition intervention to improve muscle mass, muscle strength, or physical performance in older people. They concluded that further studies were needed to provide evidence upon which public health and clinical recommendations could be based. The purpose of the present work was to update the prior systematic review and include studies published up to October 2015. METHODS: Using the electronic databases MEDLINE and EMBASE, we identified RCTs which assessed the combined effect of exercise training and nutritional supplementation on muscle strength, muscle mass, or physical performance in subjects aged 60 years and over. Study selection and data extraction were performed by two independent reviewers. RESULTS: The search strategy identified 21 additional RCTs giving a total of 37 RCTs. Studies were heterogeneous in terms of protocols for physical exercise and dietary supplementation (proteins, essential amino acids, creatine, ß-hydroxy-ß-methylbuthyrate, vitamin D, multi-nutrients, or other). In 79% of the studies (27/34 RCTs), muscle mass increased with exercise but an additional effect of nutrition was only found in 8 RCTs (23.5%). Muscle strength increased in 82.8% of the studies (29/35 RCTs) following exercise intervention, and dietary supplementation showed additional benefits in only a small number of studies (8/35 RCTS, 22.8%). Finally, the majority of studies showed an increase of physical performance following exercise intervention (26/28 RCTs, 92.8%) but interaction with nutrition supplementation was only found in 14.3% of these studies (4/28 RCTs). CONCLUSION: Physical exercise has a positive impact on muscle mass and muscle function in healthy subjects aged 60 years and older. The biggest effect of exercise intervention, of any type, has been seen on physical performance (gait speed, chair rising test, balance, SPPB test, etc.). We observed huge variations in regard to the dietary supplementation protocols. Based on the included studies, mainly performed on well-nourished subjects, the interactive effect of dietary supplementation on muscle function appears limited.

Association between teriparatide treatment persistence and adherence, and fracture incidence in Taiwan: analysis using the National Health Insurance Research Database.

UNLABELLED: Medication persistence and adherence are critical for osteoporosis outcomes. Using the Taiwan National Health Insurance Research Database, we found that persistence and adherence to teriparatide were low in Taiwanese patients with osteoporosis and that greater persistence and adherence were associated with a lower incidence of hip and other nonvertebral fractures. INTRODUCTION: The purpose of this study was to determine the persistence and adherence to teriparatide treatment in Taiwanese patients with osteoporosis, and to examine the association between persistence and adherence to teriparatide with fracture risks. METHODS: Medical and pharmacy claims for 4,692 patients with vertebral or hip fractures and teriparatide prescriptions between 2005 and 2008 were identified (Taiwan National Health Insurance Research Database). Persistence was the time from the start of treatment to the first 90-day gap between two teriparatide prescriptions. Adherence was the number of teriparatide pens (each pen is used over 1 month) prescribed over 24 months. Association of persistence and adherence to teriparatide with fracture incidence was assessed using adjusted Cox proportional hazards models. RESULTS: The proportion of patients persisting with teriparatide for >6 months and >12 months was 44.6 and 24.9 %, respectively. Over 24 months, 53.6 % of patients were adherent for >6 months and 33.9 % were adherent for >12 months. Patients persisting for >12 months had a significantly lower incidence of hip (adjusted hazard ratio [HR], 0.61 [95 % confidence interval (CI), 0.40-0.93], P = 0.0229) and nonvertebral fracture (HR, 0.79 [95 % CI, 0.63-0.99], P = 0.0462) compared with those who persisted for ≤12 months. Patients adherent for >12 months had a lower incidence of hip (HR, 0.66 [95 % CI, 0.46-0.96], P = 0.0286) and nonvertebral fracture (HR, 0.81 [95 % CI, 0.66-0.99], P = 0.0377) compared with those adherent for ≤12 months. CONCLUSIONS: Persistence and adherence to teriparatide over 24 months were low in Taiwanese patients with osteoporosis; greater adherence and persistence were associated with a lower incidence of nonvertebral fractures.

Effect of niacin on triglyceride-rich lipoprotein apolipoprotein B-48 kinetics in statin-treated patients with type 2 diabetes.

AIM: To investigate the effects of extended-release (ER) niacin on apolipoprotein B-48 (apoB-48) kinetics in statin-treated patients with type 2 diabetes (T2DM). METHODS: A total of 12 men with T2DM were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed to the alternate therapy. Postprandial metabolic studies were performed at the end of each treatment period. D3-leucine tracer was administered as subjects consumed a high-fat liquid meal. ApoB-48 kinetics were determined using stable isotope tracer kinetics with fractional catabolic rates (FCRs) and secretion rates derived using a non-steady-state compartmental model. Area-under-the-curve (AUC) and incremental AUC (iAUC) for plasma triglyceride and apoB-48 were also calculated over the 10-h period after ingestion of the fat meal. RESULTS: In statin-treated patients with T2DM, apoB-48 concentration was lower with ER niacin (8.24 ± 1.98 vs 5.48 ± 1.14 mg/l, p = 0.03) compared with statin alone. Postprandial triglyceride and apoB-48 AUC were also significantly lower on ER niacin treatment (-15 and -26%, respectively; p < 0.05), without any change to triglyceride and apoB-48 iAUC. ApoB-48 secretion rate in the basal state (3.21 ± 0.34 vs 2.50 ± 0.31 mg/kg/day; p = 0.04) and number of apoB-48-containing particles secreted in response to the fat load (1.35 ± 0.19 vs 0.84 ± 0.12 mg/kg; p = 0.02) were lower on ER niacin. ApoB-48 FCR was not altered with ER niacin (8.78 ± 1.04 vs 9.17 ± 1.26 pools/day; p = 0.79). CONCLUSIONS: ER niacin reduces apoB-48 concentration by lowering fasting and postprandial apoB-48 secretion rate. This effect may be beneficial for lowering atherogenic postprandial lipoproteins and may provide cardiovascular disease risk benefit in patients with T2DM.

Effect of omega-3 fatty acid supplementation on arterial elasticity in patients with familial hypercholesterolaemia on statin therapy.

BACKGROUND AND AIMS: Increased arterial stiffness is closely linked with raised blood pressure that contributes substantially to enhanced risk of coronary heart disease in high risk individuals with familial hypercholesterolaemia (FH). Omega-3 fatty acid (ω3-FA) supplementation has been demonstrated to lower blood pressure in subjects with a high cardiovascular disease risk. Whether ω3-FA supplementation improves arterial stiffness in FH subjects, on background statin therapy, has yet to be investigated. METHOD AND RESULTS: We carried out an 8-week randomized, crossover intervention trial to test the effect of 4 g/d ω3-FA supplementation (46% eicosapentaenoic acid and 38% docosahexaenoic acid) on arterial elasticity in 20 adults with FH on optimal cholesterol-lowering therapy. Large and small artery elasticity were measured by pulse contour analysis of the radial artery. ω3-FA supplementation significantly (P < 0.05 in all) increased large artery elasticity (+9%) and reduced systolic blood pressure (-6%) and diastolic blood pressure (-6%), plasma triglycerides (-20%), apoB concentration (-8%). In contrast, ω3-FAs had no significant effect on small artery elasticity. The change in large artery elasticity was not significantly associated with changes in systolic blood pressure or plasma triglyceride concentration. CONCLUSIONS: ω3-FA supplementation improves large arterial elasticity and arterial blood pressure independent of statin therapy in adults with FH. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.com/NCT01577056.

Association between skeletal muscle fat content and very-low-density lipoprotein-apolipoprotein B-100 transport in obesity: effect of weight loss.

AIMS: Ectopic deposition of fat in skeletal muscle is a feature of metabolic syndrome, but its specific association with very-low-density lipoprotein (VLDL)-apolipoprotein (apo) B-100 metabolism remains unclear. METHODS: We examined the association between skeletal muscle fat content and VLDL-apoB-100 kinetics in 25 obese subjects, and the responses of these variables to weight loss. The fat contents of liver, abdomen and skeletal muscle were determined by magnetic resonance imaging, and VLDL-apoB-100 kinetics were assessed using stable isotope tracers. RESULTS: In obese subjects who were insulin sensitive (homeostasis model assessment, HOMA, score ≤ 2.6, n = 12), skeletal muscle fat content was significantly associated with hepatic fat content (r = 0.636), energy intake (r = 0.694), plasma triglyceride (r = 0.644), apoB-100 (r = 0.529), glucose (r = 0.622), VLDL-apoB-100 concentrations (r = 0.860), VLDL-apoB-100 fractional catabolic rate (FCR; r = -0.581) and VLDL-apoB-100 secretion rate (r = 0.607). These associations were not found in obese subjects who were insulin resistant (HOMA score >2.6, n = 13). Of these 25 subjects, 10 obese subjects underwent a 16-week weight loss program. The low-fat diet achieved significant reduction (p < 0.05) in body weight, visceral and subcutaneous fat areas, liver and skeletal muscle fat, energy intake, triglyceride, insulin, HOMA score, VLDL-apoB100 concentrations and VLDL-apoB100 secretion rate. The percentage reduction of skeletal muscle fat with weight loss was significantly associated with the corresponding changes in VLDL-apoB100 concentration (r = 0.770, p = 0.009) and VLDL-apoB-100 secretion (r = 0.682, p = 0.030). CONCLUSIONS: Skeletal muscle fat content is associated with VLDL-apoB-100 transport. Weight loss lowers skeletal muscle fat and VLDL-apoB-100 secretion.

Atorvastatin plus omega-3 fatty acid ethyl ester decreases very-low-density lipoprotein triglyceride production in insulin resistant obese men.

AIM: To test the effect of atorvastatin (ATV) and ATV plus ω-3 FAEEs on VLDL-TG metabolism in obese, insulin resistant men. METHODS: We carried out a 6-week randomized, placebo-controlled study to examine the effect of ATV (40 mg/day) and ATV plus ω-3 FAEEs (4 g/day) on VLDL-TG metabolism in 36 insulin resistant obese men. VLDL-TG kinetics were determined using d5 -glycerol, gas chromatography-mass spectrometry and compartmental modelling. RESULTS: Compared with the placebo, ATV significantly decreased VLDL-TG concentration (-40%, p < 0.001) by increasing VLDL-TG fractional catabolic rate (FCR) (+47%, p < 0.01). ATV plus ω-3 FAEEs lowered VLDL-TG concentration to a greater degree compared with placebo (-46%, p < 0.001) or ATV monotherapy (-13%, p = 0.04). This was achieved by a reduction in VLDL-TG production rate (PR) compared with placebo (-32%, p = 0.008) or ATV (-20%, p = 0.03) as well as a reciprocal increase in VLDL-TG FCR (+42%, p < 0.05) compared with placebo. CONCLUSION: In insulin resistant, dyslipidaemic, obese men, ATV improves VLDL-TG metabolism by increasing VLDL-TG FCR. The addition of 4 g/day ω-3 FAEE to statin therapy provides further TG-lowering by lowering VLDL-TG PR.

Evaluating compliance with the care standard of proactively assessing bone health in patients with diabetes: a pilot audit of practice across Asia by the Asia Pacific Consortium on Osteoporosis (APCO).

This pilot audit explored how bone health is assessed patients with diabetes in diverse centres across Asia. Only 343 of 1092 (31%) audited patients had a bone health assessment, 27% of whom were diagnosed with osteoporosis. Quality improvement strategies are needed to address gaps in patient care in this area. PURPOSE: The Asia Pacific Consortium on Osteoporosis (APCO) Framework outlines clinical standards for assessing and managing osteoporosis. A pilot audit evaluated adherence to clinical standard 4, which states that bone health should be assessed in patients with conditions associated with bone loss and/or increased fracture risk; this report summarises the audit findings in patients with diabetes. A secondary aim was to assess the practicality and real-world use of the APCO bone health audit tool kit. METHODS: Eight centres across Asia participated in the pilot audit, selecting diabetes as the target group. Participants reviewed their practice records for at least 20 consecutively treated patients with the target condition. Questions covered routine investigations, bone health assessment, osteoporosis diagnosis, and patient referral pathways. Data were summarised descriptively. RESULTS: The participants represented public hospitals, university medical centres, and private clinics from India, Malaysia, Pakistan, Singapore, Taiwan, and Vietnam that see an estimated total of 95,000 patients with diabetes per year. Overall, only 343 of 1092 audited patients (31%) had a bone health assessment. Osteoporosis was subsequently diagnosed in 92 of 343 (27%) patients. CONCLUSION: Bone health was not assessed in most patients with diabetes. The results provide insight into current practices across diverse Asian centres and demonstrate the practical value of the audit tool kit. Participant feedback has been used to improve the tool kit. Results of this pilot audit are being used in the respective centres to inform quality improvement projects needed to overcome the gap in patient care.

Postprandial hypertriglyceridemia and cardiovascular disease: current and future therapies.

Exaggerated postprandial hypertriglyceridemia is a risk factor for cardiovascular disease. This metabolic abnormality is principally due to overproduction and/or decreased catabolism of triglyceride-rich lipoproteins (TRLs) and is a consequence of pathogenic genetic variations and other coexistent medical conditions, particularly obesity and insulin resistance. Accumulation of TRL in the postprandial state promotes the formation of small, dense low-density lipoproteins, as well as oxidative stress, inflammation, and endothelial dysfunction, all of which compound the risk of cardiovascular disease. The cardiovascular benefits of lifestyle modification (weight loss and exercise) and conventional lipid-lowering therapies (statins, fibrates, niacin, ezetimibe, and n-3 fatty acid supplementation) could involve their favorable effects on TRL metabolism. New agents, such as dual peroxisome-proliferator-activated receptor α/δ agonists, diacylglycerol, inhibitors of diacylglycerol acyltransferase 1 and microsomal triglyceride transfer protein, antisense oligonucleotides for apolipoprotein B-100 and apolipoprotein C-III, and incretin-based therapies, may enhance the treatment of postprandial lipemia, but their efficacy needs to be tested in clinical end point trials. Further work is required to develop a simple clinical protocol for investigating postprandial lipemia, as well as internationally agreed management guidelines for this type of dyslipidemia.

Does the presence of a cesarean section scar influence the site of placental implantation and subsequent migration in future pregnancies: a prospective case-control study.

OBJECTIVES: To describe placental location in the first trimester of pregnancy and subsequent placental migration in women with and without a history of previous cesarean delivery. METHODS: In this prospective case-control study, placental location was defined according to five anatomical sites in relation to the endometrial cavity. Placental localization was carried out by transabdominal ultrasound between 11 and 14 weeks' gestation. We recruited 738 women who had undergone one or more previous cesarean sections (CS) and 1856 patients without previous cesarean delivery. Comparative analysis was performed of placental location between the two groups, and to assess placental migration of those classified as being low lying at 20 and 32 weeks' gestation. RESULTS: There were significant differences in placental location between the two groups. In the CS group there were significantly more posterior and fewer fundal placentae than in the control group (47.2 vs 31.5% and 4.7 vs 15.5%, respectively). The number of previous cesarean deliveries did not have a significant effect on placental location. There was no significant difference in the incidence of anterior low-lying placenta between groups (1.5 vs 0.9%). Placental migration of the low-lying subtypes was similar in both groups (62 vs 64%). CONCLUSION: The presence of CS scars in the uterus are associated with an increase in the number of posterior placentae and a reduced number that implant in the fundus of the cavity. Migration of a low-lying placenta is independent of the presence of a CS scar in the uterus.

Penetration pattern of rhodamine dyes into enamel and dentin: confocal laser microscopy observation.

Enamel and dentin are susceptible to extrinsic and intrinsic stains. The purposes of this study were to determine the penetration pattern of Rhodamine B and dextran-conjugated Rhodamine B into the enamel and dentin as observed by confocal laser microscopy and to relate it to the penetration pattern of hydrogen peroxide commonly used as an active ingredient in tooth-whitening agents and high-molecular-weight staining molecules. Eighteen recently extracted human maxillary anterior teeth were used. Teeth were cleaned and painted with nail varnish except for the crown area above the cemento-enamel junction (CEJ). The painted teeth were then immersed in Rhodamine B and dextran-conjugated Rhodamine B (70 000 MW) for 4, 7, 10 and 15 days. Teeth were sliced to 3 mm thickness in transverse plane and mounted on a glass slide just prior to observation with confocal laser microscopy. Rhodamine B and dextran-conjugated Rhodamine B readily penetrated into the enamel and dentin when exposed for 4 and 7 days, respectively. Rhodamine B penetrated along the interprismatic spaces of the enamel into the dentin. The penetration was accentuated in sections with existing crack lines in the enamel. Rhodamine B was readily absorbed into the dentinal tubules at the dentino-enamel junction and continued to penetrate through the dentin via the dentinal tubules into the pre-dentin. Within the limitations of this study, it is concluded that Rhodamine B and dextran-conjugated Rhodamine B when applied to the external surface of the tooth readily penetrate into the enamel and dentin via the interprismatic spaces in the enamel and dentinal tubules in the dentin, suggesting that stain molecules and bleaching agents possibly exhibit similar penetration pathways.

Successful treatment of mucormycosis infection after liver transplantation: report of a case and review of the literature.

Mucormycosis (zygomycosis) is a rare opportunistic fungal infection mainly affecting patients with diabetes mellitus, immunodeficiency, malignancies and solid organ transplant. We present a 55-year-old female with a mucormycosis infection primarily affecting the paranasal sinuses after liver transplantation. The patient presented with a one-week history of right-sided occipital headache and gradual loss of vision in the right eye just 6 months after liver transplantation. Imaging studies revealed a right-sided sphenoiditis with orbital apex involvement. The patient underwent endoscopic sinus surgery and the histology confirmed the diagnosis of mucormycosis. Aggressive surgical ablation of the infected parts, along with antifungal treatment and adjustment of her immunosuppressive maintenance resulted in a good outcome and long-term survival.

Influence of age on PPV of sonographic BI-RADS categories 3, 4, and 5.

PURPOSE: The purpose of this retrospective study was to calculate the positive predictive value (PPV) of sonographic Breast Imaging Reporting and Data System (BI-RADS) categories 3, 4, and 5 in different age groups to investigate whether age influences the PPV of the BI-RADS category in breast ultrasound. MATERIALS AND METHODS: From our sonography-guided core biopsy database of breasts between 2006 and 2008, we identified 2817 BI-RADS category 3, 4, and 5 lesions with known pathological diagnosis in 2587 women, all of whom underwent the earlier breast assessment via ultrasound with a sonographic BI-RADS lexicon and later sonography-guided core biopsy. All lesions were classified into three age groups (< 45, 45 - 59, and > 59 years). The age-related PPVs of each BI-RADS category among three age groups were calculated on the basis of pathological diagnoses and were compared using a χ(2)-test. RESULTS: The overall PPV of each BI-RADS category was 2.2 % in category 3, 6.5 % in category 4a, 35.2 % in category 4b, 79.6 % in category 4c, and 99.6 % in category 5. The age-related PPVs of category 3 varied significantly among the three age groups (0.9 % versus 3.9 % versus 2.0 % p = 0.048), and notably, the age-related PPV in group 2 was higher than the others. Additionally, there was a significant positive association between the age-related PPVs and increasing age in categories 4a and 4b (4a, p < 0.0001 and 4b, p = 0.0139), but not in categories 4c and 5 (4c, p = 0.1853 and 5, p = 0.2871). CONCLUSION: The incidence of female breast cancer differs not only in different sonographic BI-RADS categories, but also in different age groups. Therefore, more attention should be paid to the special age group that we found for sonographic BI-RADS categories 3, 4a, and 4b.

The accuracy of optical scanning: influence of convergence and die preparation.

The purpose of this study was to determine the reliability of the data acquisition and modeling process of laser and white light scanners by evaluating the reproducibility of digitized simulated crowns with different convergences. A secondary purpose was to analyze the influence of die preparation by testing this hypothesis with a set of dies without ditching compared with a set with well-defined margins. Ditching or trimming the die defines the position of the margin and acts as a guide to gingival contour when the restoration is being waxed. Two light scanners (a white light optical scanner [Steinbichler Gmbh, Neubeuern, Germany] and red laser light scanner [TurboDent System, Taichung, Taiwan]) were evaluated. Two sets of simulated crowns were fabricated as cone frustrum models with a total occlusal convergence (TOC) of 0°, 5°, 10°, 15°, 20°, and 25° and a 9-mm base and 3-mm height using a precision milling machine and computer-aided design/computer-aided manufacturing (CAD/CAM) technique. One set of the dies was ditched immediately below the finish line to enhance marginal definition. Each die was optically digitized five times directly with the two different measuring systems. The area of each triangle in the scan that is occlusal to the margin line was calculated and summed to produce the final surface area measurement provided. The digitizing error was compared with the computed surface area of the original master die sets and compared with a paired t-test (df=4; 95% CI). There was no difference in accuracy of the untrimmed dies between the two systems evaluated. We also did not find any difference in the 0° (p=0.12) and 5° degree (p=0.21) groups among the ditched dies. However, when the TOC exceeded 5°, there was a significant difference between the two groups, with the laser groups having a smaller error percentage. Three-dimensional light scanning was not affected by the convergence angle except in the 0°-5° range. Trimming the dies greatly affected the accuracy of scanning.