Reduced Insulin Resistance and Oxidative Stress in a Mouse Model of Metabolic Syndrome following Twelve Weeks of Citrus Bioflavonoid Hesperidin Supplementation: A Dose-Response Study.

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and neurodegenerative diseases. Oxidative stress and inflammation are key drivers of MetS. Hesperidin, a citrus bioflavonoid, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on MetS are not fully established. We aimed to determine the optimal dose of hesperidin required to improve oxidative stress, systemic inflammation, and glycemic control in a novel mouse model of MetS. Male 5-week-old C57BL/6 mice were fed a high-fat, high-salt, high-sugar diet (HFSS; 42% kcal fat content in food and drinking water with 0.9% saline and 10% high fructose corn syrup) for 16 weeks. After 6 weeks of HFSS, mice were randomly allocated to either the placebo group or low- (70 mg/kg/day), mid- (140 mg/kg/day), or high-dose (280 mg/kg/day) hesperidin supplementation for 12 weeks. The HFSS diet induced significant metabolic disturbances. HFSS + placebo mice gained almost twice the weight of control mice (p < 0.0001). Fasting blood glucose (FBG) increased by 40% (p < 0.0001), plasma insulin by 100% (p < 0.05), and HOMA-IR by 150% (p < 0.0004), indicating insulin resistance. Hesperidin supplementation reduced plasma insulin by 40% at 140 mg/kg/day (p < 0.0001) and 50% at 280 mg/kg/day (p < 0.005). HOMA-IR decreased by 45% at both doses (p < 0.0001). Plasma hesperidin levels significantly increased in all hesperidin groups (p < 0.0001). Oxidative stress, measured by 8-OHdG, was increased by 40% in HFSS diet mice (p < 0.001) and reduced by 20% with all hesperidin doses (p < 0.005). In conclusion, hesperidin supplementation reduced insulin resistance and oxidative stress in HFSS-fed mice, demonstrating its dose-dependent therapeutic potential in MetS.

Hydroxychloroquine Induced Cardiotoxicity: A Case Series.

Hydroxychloroquine (HCQ) induced cardiotoxicity is a rare diagnosis and is often associated with chronic use of the medication. It has been shown that chronic HCQ use is associated with a drug-induced cardiomyopathy mainly driven by acquired lysosomal storage defects leading to hypertrophy and conduction abnormalities. As the only proven treatment is the discontinuation of the offending agent, prompt recognition is required to avoid further exposure to the drug and potential progression of disease. History, physical examination and advanced imaging modalities are useful diagnostic tools, but more invasive testing with an endomyocardial biopsy is required for definitive diagnosis. We present a descriptive case series of ten patients that were diagnosed with biopsy proven HCQ cardiotoxicity.

Extra virgin olive oil improves HDL lipid fraction but not HDL-mediated cholesterol efflux capacity: a double-blind, randomised, controlled, cross-over study (OLIVAUS).

Olive oil (OO) polyphenols have been shown to improve HDL anti-atherogenic function, thus demonstrating beneficial effects against cardiovascular risk factors. The aim of the present study was to investigate the effect of extra virgin high polyphenol olive oil (HPOO) v. low polyphenol olive oil (LPOO) on the capacity of HDL to promote cholesterol efflux in healthy adults. In a double-blind, randomised cross-over trial, fifty participants (aged 38·5 (sd 13·9) years, 66 % females) were supplemented with a daily dose (60 ml) of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for 3 weeks. Following a 2-week washout period, participants crossed over to the alternate treatment. Serum HDL-cholesterol efflux capacity, circulating lipids (i.e. total cholesterol, TAG, HDL, LDL) and anthropometrics were measured at baseline and follow-up. No significant between-group differences were observed. Furthermore, no significant changes in HDL-cholesterol efflux were found within either the LPOO and HPOO treatment arms; mean changes were 0·54 % (95 % CI (0·29, 1·37)) and 0·10 % (95 % CI (0·74, 0·94)), respectively. Serum HDL increased significantly after LPOO and HPOO intake by 0·13 mmol/l (95 % CI (0·04, 0·22)) and 0·10 mmol/l (95 % CI (0·02, 0·19)), respectively. A small but significant increase in LDL of 0·14 mmol/l (95 % CI (0·001, 0·28)) was observed following the HPOO intervention. Our results suggest that additional research is warranted to further understand the effect of OO with different phenolic content on mechanisms of cholesterol efflux via different pathways in multi-ethnic populations with diverse diets.

The anti-inflammatory effects of a Mediterranean diet: a review.

PURPOSE OF REVIEW: Chronic noncommunicable diseases remain the leading cause of morbidity and mortality worldwide and the majority are preventable with a healthy diet and lifestyle, but controversy remains as to the best approach. Greater adherence to a traditional Mediterranean diet has consistently been associated with lower morbidity and mortality from cardiovascular disease, diabetes and many cancers, and lower all-cause mortality. Despite the well known benefits on chronic disease risk there remains some scepticism as to the effects of this dietary pattern across populations outside the Mediterranean and the mechanisms of action of this traditional plant-based dietary pattern.This narrative review aims to summarize the latest evidence on the health protective effects of a traditional Mediterranean diet on chronic noncommunicable diseases, specifically focussing on the anti-inflammatory effects of this highly published dietary pattern. RECENT FINDINGS: Recent high-quality evidence now supports a Mediterranean diet in secondary prevention of cardiovascular disease with impacts on atherosclerosis progression, likely through reduction of systemic inflammation and irrespective of changes in cholesterol or weight. The Mediterranean diet has a low Dietary Inflammatory Index illustrating its anti-inflammatory potential. This dietary pattern beneficially modulates the gut microbiota and immune system, including emerging evidence for efficacy against severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019). Emerging evidence shows clinicians are not routinely recommending a Mediterranean diet despite well known evidence due to barriers such as lack of training, patient materials and concerns about potential patient adherence. SUMMARY: The physiological mechanisms of action of this healthy diet pattern are becoming better understood to be multisystem and involving the gut. Larger controlled trials investigating mechanistic effects in broader non-Mediterranean populations are warranted. Although reflected in therapeutic guidelines for chronic disease management worldwide there are individual, clinical practice and health system barriers to its implementation that need a multisectoral approach to address.

Extra virgin olive oil high in polyphenols improves antioxidant status in adults: a double-blind, randomized, controlled, cross-over study (OLIVAUS).

PURPOSE: Olive oil polyphenols have been associated with cardiovascular health benefits. This study examined the antioxidant and anti-inflammatory effect of extra-virgin high polyphenol olive oil (HPOO) vs. low polyphenol olive oil (LPOO) in healthy Australian adults. METHODS: In a double-blind cross-over trial, 50 participants (aged 38.5 ± 13.9 years, 66% females) were randomized to consume 60 mL/day of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for three weeks. Following a 2-week wash-out period, participants crossed-over to the alternate treatment. Plasma oxidized low-density lipoprotein (ox-LDL), total antioxidant capacity (TAC), high-sensitivity C-reactive protein (hs-CRP) and anthropometrics were measured at baseline and follow-up. RESULTS: Fourty-three participants completed the study. Although there were no significant differences between treatments in the total sample, plasma ox-LDL decreased by 6.5 mU/mL (95%CI - 12.4 to - 0.5) and TAC increased by 0.03 mM (95% CI 0.006-0.05) only in the HPOO arm. Stratified analyses were also performed by cardiovascular disease risk status defined by abdominal obesity (WC > 94 cm in males, > 80 cm in females) or inflammation (hs-CRP > 1 mg/L). In the subgroup with abdominal obesity, ox-LDL decreased by 13.5 mU/mL (95% CI - 23.5 to - 3.6) and TAC increased by 0.04 mM (95% CI 0.006-0.07) only after HPOO consumption. In the subgroup with inflammation, hs-CRP decreased by 1.9 mg/L (95% CI - 3.7 to -0.1) only in the HPOO arm. CONCLUSIONS: Although there were no significant differences between treatments, the changes observed after HPOO consumption demonstrate the antioxidant and anti-inflammatory effect of this oil, which is more pronounced in adults with high cardiometabolic risk (Clinical Trial Registration: ACTRN12618000706279).

A Step-By-Step Method to Detect Neutralizing Antibodies Against AAV using a Colorimetric Cell-Based Assay.

Recombinant adeno-associated viruses (rAAV) have proven to be a safe and successful vector for transferring genetic material to treat various health conditions in both the laboratory and the clinic. However, pre-existing neutralizing antibodies (NAbs) against AAV capsids pose an ongoing challenge for the successful administration of gene therapies in both large animal experimental models and human populations. Preliminary screening for host immunity against AAV is necessary to ensure the efficacy of AAV-based gene therapies as both a research tool and as a clinically viable therapeutic agent. This protocol describes a colorimetric in vitro assay to detect neutralizing factors against AAV serotype 6 (AAV6). The assay utilizes the reaction between an AAV encoding an alkaline phosphatase (AP) reporter gene and its substrate NBT/BCIP, which generates an insoluble quantifiable purple stain upon combination. In this protocol, serum samples are combined with an AAV expressing AP and incubated to permit potential neutralizing activity to occur. Virus serum mixture is subsequently added to cells to allow for viral transduction of any AAVs that have not been neutralized. The NBT/BCIP substrate is added and undergoes a chromogenic reaction, corresponding to viral transduction and neutralizing activity. The proportion of area colored is quantitated using a free software tool to generate neutralizing titers. This assay displays a strong positive correlation between coloration and viral concentration. Assessment of serum samples from sheep before and after administration of a recombinant AAV6 led to a dramatic increase in neutralizing activity (125 to >10,000-fold increase). The assay displayed adequate sensitivity to detect neutralizing activity in >1:32,000 serum dilutions. This assay provides a simple, rapid, and cost-effective method to detect NAbs against AAVs.

Twelve-Week Mediterranean Diet Intervention Increases Citrus Bioflavonoid Levels and Reduces Inflammation in People with Type 2 Diabetes Mellitus.

The benefits of a Mediterranean Diet (MedDiet) in the management of diabetes have been reported, but the contribution of polyphenol-rich citrus fruit has not been studied widely. Here, we report the sub-study findings of a previously conducted MedDiet intervention clinical trial in patients with type 2 diabetes mellitus (T2DM), where we aimed to measure the diet intervention effects on plasma citrus bioflavonoids levels and biomarkers of inflammation and oxidative stress. We analysed plasma samples from 19 (of original 27) participants with T2DM who were randomly assigned to consume the MedDiet intervention or their usual diet for 12 weeks and then crossed over to the alternate diet. Compared with baseline, MedDiet significantly increased levels of the citrus bioflavonoids naringin, hesperitin and hesperidin (by 60%, 58% and 39%, respectively, p < 0.05) and reduced plasma levels of the pro-inflammatory cytokine IL-6 (by 49%, p = 0.016). Oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) decreased by 32.4% (p = 0.128). Usual diet did not induce these beneficial changes. The reduced inflammatory profile of T2DM participants may, in part, be attributed to the anti-inflammatory actions of citrus bioflavonoids. Together with indications of improved oxidative stress, these findings add to the scientific evidence base for beneficial consumption of citrus fruit in the MedDiet pattern.

The Effect of High Polyphenol Extra Virgin Olive Oil on Blood Pressure and Arterial Stiffness in Healthy Australian Adults: A Randomized, Controlled, Cross-Over Study.

Extra virgin olive oil (EVOO) is suggested to be cardioprotective, partly due to its high phenolic content. We investigated the effect of extra virgin high polyphenol olive oil (HPOO) versus low polyphenol olive oil (LPOO) on blood pressure (BP) and arterial stiffness in healthy Australian adults. In a double-blind, randomized, controlled cross-over trial, 50 participants (age 38.5 ± 13.9 years, 66% female) were randomized to consume 60 mL/day of either HPOO (360 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for three weeks. Following a two-week washout period, participants crossed over to consume the alternate oil. Anthropometric data, peripheral BP, central BP and arterial stiffness were measured at baseline and follow up. No significant differences were observed in the changes from baseline to follow up between the two treatments. However, a significant decrease in peripheral and central systolic BP (SBP) by 2.5 mmHg (95% CI: -4.7 to -0.3) and 2.7 mmHg (95% CI: -4.7 to -0.6), respectively, was observed after HPOO consumption. Neither olive oil changed diastolic BP (DBP) or measures of arterial stiffness. The reductions in SBP after HPOO consumption provide evidence for a potentially widely accessible dietary intervention to prevent cardiovascular disease in a multiethnic population. Longer intervention studies and/or higher doses of EVOO polyphenols are warranted to elucidate the potential effect on DBP and arterial stiffness.

Effect of high polyphenol extra virgin olive oil on markers of cardiovascular disease risk in healthy Australian adults (OLIVAUS): A protocol for a double-blind randomised, controlled, cross-over study.

BACKGROUND: Previous clinical studies have suggested that high polyphenol extra virgin olive oil (EVOO) provides a superior cardioprotective effect compared to low polyphenol olive oil. However, further studies are required to replicate these results in non-Mediterranean populations. AIM: To investigate the effect of high polyphenol EVOO versus low polyphenol olive oil with known polyphenol composition on markers of cardiovascular disease risk in a healthy non-Mediterranean cohort. METHODS: In a double-blind randomised cross-over trial, the present study will examine the effect of high polyphenol EVOO versus low polyphenol olive oil in 50 healthy participants. Each intervention phase will be 3 weeks long with a 2-week washout period between each phase. Outcomes to be assessed include HDL cholesterol efflux, oxidised LDL, blood lipids, C-reactive protein, arterial stiffness, blood pressure and cognitive function. Dietary intake, physical activity levels and anthropometry will also be collected. DISCUSSION: Because of the rigorous trial design, novel and clinically relevant outcomes, the use of a well-characterised EVOO, and, in contrast to the current literature, the non-Mediterranean study population, the present study will provide a significant contribution to the understanding of the clinical importance of polyphenol intake in the Australian sociocultural context.

The effect of high-polyphenol extra virgin olive oil on cardiovascular risk factors: A systematic review and meta-analysis.

The polyphenol fraction of extra-virgin olive oil may be partly responsible for its cardioprotective effects. The aim of this systematic review and meta-analysis was to evaluate the effect of high versus low polyphenol olive oil on cardiovascular disease (CVD) risk factors in clinical trials. In accordance with PRISMA guidelines, CINAHL, PubMed, Embase and Cochrane databases were systematically searched for relevant studies. Randomized controlled trials that investigated markers of CVD risk (e.g. outcomes related to cholesterol, inflammation, oxidative stress) were included. Risk of bias was assessed using the Jadad scale. A meta-analysis was conducted using clinical trial data with available CVD risk outcomes. Twenty-six studies were included. Compared to low polyphenol olive oil, high polyphenol olive oil significantly improved measures of malondialdehyde (MD: -0.07µmol/L [95%CI: -0.12, -0.02µmol/L]; I2: 88%; p = 0.004), oxidized LDL (SMD: -0.44 [95%CI: -0.78, -0.10µmol/L]; I2: 41%; P = 0.01), total cholesterol (MD 4.5 mg/dL [95%CI: -6.54, -2.39 mg/dL]; p<0.0001) and HDL cholesterol (MD 2.37 mg/dL [95%CI: 0.41, 5.04 mg/dL]; p = 0.02). Subgroup analyses and individual studies reported additional improvements in inflammatory markers and blood pressure. Most studies were rated as having low-to-moderate risk of bias. High polyphenol oils confer some CVD-risk reduction benefits; however, further studies with longer duration and in non-Mediterranean populations are required.

Simulation: An Effective Method of Teaching Cosmetic Botulinum Toxin Injection Technique.

BACKGROUND: Learning to inject botulinum toxin for cosmetic purposes is difficult for beginners, given the nature of the procedure and patient population. Simulation training is an effective modality for medical professionals to acquire skills in an environment that provides low stress and ample opportunity for questions and correction of mistakes. OBJECTIVES: Compare posttraining comfort, knowledge, and practical botulinum toxin injection scores among trainees who underwent simulation vs video training only. METHODS: A total of 20 nurse practitioners, physician assistants, and resident physicians underwent cosmetic botulinum toxin injection training either through lecture and video, or lecture and hands-on simulation training. Comfort, knowledge, and practical test scores were recorded and compared between the groups. RESULTS: There was no evidence of a statistically significant difference in comfort or knowledge scores between simulation and video groups. The median (range) practical score was significantly higher in the simulation group compared to the video group (59.0 [31-60] vs 44.5 [27-57]; P < 0.01). CONCLUSIONS: Despite feeling similarly comfortable and having similar written knowledge test scores, the trainees who underwent simulation training had significantly higher hands-on practical test scores compared to trainees who underwent video training only for cosmetic botulinum toxin injections.

The AUStralian MEDiterranean Diet Heart Trial (AUSMED Heart Trial): A randomized clinical trial in secondary prevention of coronary heart disease in a multiethnic Australian population: Study protocol.

The Mediterranean diet was first characterized as a heart-protective diet in the 1960s. The significant cardioprotective effects of the Mediterranean diet in comparison to the standard-care low-fat diet have been established in the primary prevention of cardiovascular disease (CVD); however, there is insufficient evidence in secondary prevention research to influence the current standard of care. Opportunity exists to assess the Mediterranean diet as a therapeutic target for secondary CVD prevention within Australia's ethnoculturally diverse communities. The AUSMED Heart Trial is a multisite randomized controlled trial that will evaluate the efficacy of the Mediterranean diet for secondary prevention of CVD in the Australian health care setting. This trial aims to evaluate the effect of a 6-month Mediterranean diet intervention (delivered by dietitians) versus a "standard-care" low-fat diet in reducing the composite incidence of cardiovascular events at 12 months and at trial end in participants with documented evidence of a previous acute myocardial infarction at trial entry. The quality of the diet at baseline and follow-up will be assessed using comprehensive dietary questionnaires and diaries as well as relevant dietary biomarkers (such as urinary polyphenols and erythrocyte fatty acids). Cardiovascular risk markers, including novel measures of immune and inflammatory status, endothelial function, vascular compliance, platelet activity, and body composition, will be collected to explore possible mechanisms for treatment effect. Cost-effectiveness will also be estimated to support policy translation. We plan to recruit 1,032 participants (516 per arm) from cardiology clinics in major Australian hospitals in Melbourne, Adelaide, and Brisbane.

Randomization to 6-month Mediterranean diet compared with a low-fat diet leads to improvement in Dietary Inflammatory Index scores in patients with coronary heart disease: the AUSMED Heart Trial.

A higher dietary inflammatory index (DII®) score is associated with inflammation and incidence of coronary heart disease (CHD). We hypothesized that a Mediterranean diet (MedDiet) intervention would reduce DII score. We assessed dietary data from a randomized controlled trial comparing 6-month MedDiet versus low-fat diet intervention, in patients with CHD. We aimed to determine the DII scores of the prescribed diets' model meal plans, followed by whether dietary intervention led to lower (i.e., more anti-inflammatory) DII scores and consequently lower high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (hs-IL-6). DII scores were calculated from 7-day food diaries. The MedDiet meal plan had a markedly lower DII score than the low-fat diet meal plan (-4.55 vs. -0.33, respectively). In 56 participants who completed the trial (84% male, mean age 62 ±â€¯9 years), the MedDiet group significantly reduced DII scores at 6 months (n = 27; -0.40 ±â€¯3.14 to -1.74 ±â€¯2.81, P = .008) and the low-fat diet group did not change (n = 29; -0.17 ±â€¯2.27 to 0.05 ±â€¯1.89, P = .65). There was a significant post-intervention adjusted difference in DII score between groups (compared to low-fat, MedDiet decreased by -1.69 DII points; P = .004). When compared to the low-fat diet, the MedDiet non-significantly reduced hs-IL-6 (-0.32 pg/mL, P = .29) and increased hs-CRP (+0.09 mg/L, P = .84). These findings demonstrated that MedDiet intervention significantly reduced DII scores compared to a low-fat diet. However, in this small cohort of patients with CHD this did not translate to a significant improvement in measured inflammatory markers. The effect of improvement in DII with MedDiet should be tested in larger intervention trials and observational cohorts.

Improvement in dietary inflammatory index score after 6-month dietary intervention is associated with reduction in interleukin-6 in patients with coronary heart disease: The AUSMED heart trial.

The Dietary Inflammatory Index (DII) was designed to measure the inflammatory potential of one's diet. Evidence from observational studies supports that a higher (ie, more pro-inflammatory) DII score is associated with inflammation and cardiometabolic diseases. We hypothesized that reduction in DII score would improve inflammatory cytokines. To test this hypothesis, we assessed data from a dietary intervention trial in patients with diagnosed coronary heart disease (CHD) to determine whether reduction in DII scores through healthy diets is linked to improvement in inflammatory and related cardiometabolic risk markers. Participants (n = 65, 83% male) were randomized to a Mediterranean diet or low-fat diet intervention for 6-months. Anthropometry, body composition and blood markers were measured and DII scores were calculated from 7-day food diaries. After 6-months, in participants who completed the intervention (n = 56), reduction in DII score correlated significantly with reduction in high sensitivity interleukin-6 (hs-IL-6) (r = 0.34, 95% CI 0.05, 0.56) and triglycerides (r = -0.30, 95% CI -0.51, -0.06) but not with C-reactive protein, adiponectin, glucose, body composition or anthropometry. The adjusted mean difference in hs-IL-6 and triglycerides between the highest and lowest tertiles of DII improvement was -0.47 pg/mL (95% CI 0.41, 1.10) and +0.30 mmol/L (95% CI 1.06, 1.59), respectively. The present study found that improvement in DII score through healthy diet intervention was linked with reduced levels of hs-IL-6, but also increased triglycerides, in adult Australian patients with CHD. Future research is warranted to investigate the impact of change in DII on cardiometabolic risk markers in larger cohorts, other disease populations or healthy subjects and with longer-term follow up.

Adeno-Associated Virus Gene Therapy: Translational Progress and Future Prospects in the Treatment of Heart Failure.

Despite advances in treatment over the past decade, heart failure remains a significant public health burden and a leading cause of death in the developed world. Gene therapy provides a promising approach for preventing and reversing cardiac abnormalities, however, clinical application has shown limited success to date. A substantial effort is being invested into the development of recombinant adeno-associated viruses (AAVs) for cardiac gene therapy as AAV gene therapy offers a high safety profile and provides sustained and efficient transgene expression following a once-off administration. Due to the physiological, anatomical and genetic similarities between large animals and humans, preclinical studies using large animal models for AAV gene therapy are crucial stepping stones between the laboratory and the clinic. Many molecular targets selected to treat heart failure using AAV gene therapy have been chosen because of their potential to regulate and restore cardiac contractility. Other genes targeted with AAV are involved with regulating angiogenesis, beta-adrenergic sensitivity, inflammation, physiological signalling and metabolism. While significant progress continues to be made in the field of AAV cardiac gene therapy, challenges remain in overcoming host neutralising antibodies, improving AAV vector cardiac-transduction efficiency and selectivity, and optimising the dose, route and method of delivery.

Endogenous Annexin-A1 Regulates Haematopoietic Stem Cell Mobilisation and Inflammatory Response Post Myocardial Infarction in Mice In Vivo.

Endogenous anti-inflammatory annexin-A1 (ANX-A1) plays an important role in preserving left ventricular (LV) viability and function after ischaemic insults in vitro, but its long-term cardioprotective actions in vivo are largely unknown. We tested the hypothesis that ANX-A1-deficiency exaggerates inflammation, haematopoietic stem progenitor cell (HSPC) activity and LV remodelling in response to myocardial ischaemia in vivo. Adult ANX - A1 -/- mice subjected to coronary artery occlusion exhibited increased infarct size and LV macrophage content after 24-48 h reperfusion compared with wildtype (WT) counterparts. In addition, ANX - A1 -/- mice exhibited greater expansion of HSPCs and altered pattern of HSPC mobilisation 8 days post-myocardial infarction, with increased circulating neutrophils and platelets, consistent with increased cardiac inflammation as a result of increased myeloid invading injured myocardium in response to MI. Furthermore, ANX - A1 -/- mice exhibited significantly increased expression of LV pro-inflammatory and pro-fibrotic genes and collagen deposition after MI compared to WT counterparts. ANX-A1-deficiency increased cardiac necrosis, inflammation, hypertrophy and fibrosis following MI, accompanied by exaggerated HSPC activity and impaired macrophage phenotype. These findings suggest that endogenous ANX-A1 regulates mobilisation and differentiation of HSPCs. Limiting excessive monocyte/neutrophil production may limit LV damage in vivo. Our findings support further development of novel ANX-A1-based therapies to improve cardiac outcomes after MI.

Development and validation of a prediction model for adenoma detection during screening and surveillance colonoscopy with comparison to actual adenoma detection rates.

OBJECTIVE: The adenoma detection rate (ADR) varies widely between physicians, possibly due to patient population differences, hampering direct ADR comparison. We developed and validated a prediction model for adenoma detection in an effort to determine if physicians' ADRs should be adjusted for patient-related factors. MATERIALS AND METHODS: Screening and surveillance colonoscopy data from the cross-sectional multicenter cluster-randomized Endoscopic Quality Improvement Program-3 (EQUIP-3) study (NCT02325635) was used. The dataset was split into two cohorts based on center. A prediction model for detection of ≥1 adenoma was developed using multivariable logistic regression and subsequently internally (bootstrap resampling) and geographically validated. We compared predicted to observed ADRs. RESULTS: The derivation (5 centers, 35 physicians, overall-ADR: 36%) and validation (4 centers, 31 physicians, overall-ADR: 40%) cohort included respectively 9934 and 10034 patients (both cohorts: 48% male, median age 60 years). Independent predictors for detection of ≥1 adenoma were: age (optimism-corrected odds ratio (OR): 1.02; 95%-confidence interval (CI): 1.02-1.03), male sex (OR: 1.73; 95%-CI: 1.60-1.88), body mass index (OR: 1.02; 95%-CI: 1.01-1.03), American Society of Anesthesiology physical status class (OR class II vs. I: 1.29; 95%-CI: 1.17-1.43, OR class ≥III vs. I: 1.57; 95%-CI: 1.32-1.86), surveillance versus screening (OR: 1.39; 95%-CI: 1.27-1.53), and Hispanic or Latino ethnicity (OR: 1.13; 95%-CI: 1.00-1.27). The model's discriminative ability was modest (C-statistic in the derivation: 0.63 and validation cohort: 0.60). The observed ADR was considerably lower than predicted for 12/66 (18.2%) physicians and 2/9 (22.2%) centers, and considerably higher than predicted for 18/66 (27.3%) physicians and 4/9 (44.4%) centers. CONCLUSION: The substantial variation in ADRs could only partially be explained by patient-related factors. These data suggest that ADR variation could likely also be due to other factors, e.g. physician or technical issues.

Impact of an Endoscopic Quality Improvement Program Focused on Adenoma Detection on Sessile Serrated Adenoma/Polyp Detection.

BACKGROUND: Sessile serrated adenomas/polyps (SSA/P) are an under-recognized disease with a unique malignant pathway. Improved endoscopic recognition and pathological interpretation is needed. AIMS: To determine whether an educational intervention that improved adenoma detection rate (ADR) could improve SSA/P detection rate after reclassification of previously termed "hyperplastic" polyps. METHODS: We reanalyzed data from a prospective randomized trial of an educational intervention aimed at increasing ADR. All hyperplastic polyps ≥6 mm reported in a previously published study were rereviewed and reclassified using standardized criteria for serrated lesions. Detection rates of sessile serrated adenomas/polyps and other clinically relevant serrated polyps were calculated in the baseline and post-training phases of the original study. RESULTS: Of 263 available for rereview, 33 (12.5%) were reclassified as SSA/P (N = 32) or traditional serrated adenoma (TSA) (N = 1). Reclassification was more common in the right colon (18 vs. 8%, p = 0.02). Baseline SSA/P detection rate was 0.7% in the untrained group and 1.3% in the trained group. Post-training, the SSA/P detection rate increased to 2.1 and 1.5%, respectively. The clinically relevant serrated polyp detection rate at baseline was 14.2% in the untrained group and 11.3% in the trained group. After the educational intervention, the clinically relevant serrated polyp detection rates increased to 16.5 and 14.8% in the untrained and trained groups, respectively. The estimated odds of an endoscopist detecting either a SSA/P or other clinically relevant serrated polyp during colonoscopy increased by only 3% with the educational intervention (OR 1.03, 95% CI 0.61-1.74, p = 0.91). CONCLUSIONS: Pathological re-interpretation of larger serrated polyps resulted in the reclassification of 12.5% of lesions. Quality improvement methods focused on adenoma detection did not impact SSA/P detection, and thus specific methods for serrated polyp detection are needed.

Prevalence of BCL-2/J(H) Translocation in Healthy African Americans.

The translocation t(14;18)(q32;q21) (BCL-2/J(H)) is present in over 80 % of all follicular lymphomas and is detectable in peripheral blood lymphocytes (PBL) of healthy individuals. The prevalence of this translocation has not been studied in African Americans (AAs). Given the higher incidence of follicular lymphomas in whites compared to AAs in the United States (USA), we hypothesized that the translocation prevalence in the blood of AAs would be lower. DNA was isolated from PBL from blood samples collected from participants from FL. Polymerase chain reaction was performed on the BCL-2/J(H) major (MBC) and minor breakpoint cluster (mBC) regions. Eight of the 77 (10.4 %) blood samples from AA participants were positive for MBC (95 % CI, 4.6-19.5 %), and three (3.9 %) were positive for mBC (95 % CI, 0.81-10.97 %) of BCL-2/J(H), with a total of 11 (14.3 %) participants with positive samples (95 % CI, 7.35-24.13 %). In 167 white patient samples, 22 (13.2 %; 95 % CI, 8.44-19.26 %) were positive for MBC, and five (3.0 %; 95 % CI, 0.98-6.85 %) were positive for mBC, with a total of 25 (15 %) participants with positive samples (CI, 9.93-21.30 %). The prevalence of t(14;18)(q32;q21) is not significantly different among AAs and whites from the USA. The lower prevalence of follicular lymphomas in AAs compared with whites is likely a result of differences in secondary molecular alterations involved in follicular lymphoma development. This study is the first report of prevalence of t(14;18) in an AA cohort.

Diffusion of Robotic Technology Into Urologic Practice has Led to Improved Resident Physician Robotic Skills.

OBJECTIVE: To investigate whether propagation of robotic technology into urologic practice and training programs has improved baseline urology resident trainee robotic skills. DESIGN: Questionnaires were completed by each urology resident trainee participating in a training course and asked about access to robotic simulation, robot experience, and console time. Baseline resident trainee scores on the Mimic Robotic Simulator (Mimic Technologies, Inc., Seattle, WA) from 27 participants of 2012 course were compared with the 2015 scores of 34 trainees on 4 standard Mimic exercises using Wilcoxon rank-sum tests. p = 0.05 or less were considered statistically significant. PARTICIPANTS AND SETTING: Totally, 34 resident trainees from 17 programs in the Southeast Section of the American Urological Association participated in an annual 2-day robotic training course. RESULTS: Overall score, economy of motion score, and time to complete exercise were all significantly better in the 2015 trainee group compared with the 2012 trainee group (p < 0.001) for the Peg Board 1, Camera Targeting 2, and Energy Dissection exercises. Overall scores for needle targeting improved between 2012 and 2015 (p = 0.04). Trainee access to a simulator was not associated with overall score on any of the 4 exercises in the 2015 group. In the 2015 group, actual robotic console time was associated with better overall scores in Camera Targeting 2 (p = 0.02) and Peg Board 1 (p = 0.04). CONCLUSIONS: Baseline resident trainee performance on basic robotic simulator exercises has improved over the past 3 years irrespective of robotic simulator access or console time.