Gut microbiota and metabolomics profiles in patients with chronic stable angina and acute coronary syndrome.

Cardiovascular disease (CVD) is the leading cause of death worldwide. The gut microbiota and its associated metabolites may be involved in the development and progression of CVD, although the mechanisms and impact on clinical outcomes are not fully understood. This study investigated the gut microbiome profile and associated metabolites in patients with chronic stable angina (CSA) and acute coronary syndrome (ACS) compared with healthy controls. Bacterial alpha diversity in stool from patients with ACS or CSA was comparable to healthy controls at both baseline and follow-up visits. Differential abundance analysis identified operational taxonomic units (OTUs) assigned to commensal taxa differentiating patients with ACS from healthy controls at both baseline and follow-up. Patients with CSA and ACS had significantly higher levels of trimethylamine N-oxide compared with healthy controls (CSA: 0.032 ± 0.023 mmol/L, P < 0.01 vs. healthy, and ACS: 0.032 ± 0.023 mmol/L, P = 0.02 vs. healthy, respectively). Patients with ACS had reduced levels of propionate and butyrate (119 ± 4 vs. 139 ± 5.1 µM, P = 0.001, and 14 ± 4.3 vs. 23.5 ± 8.1 µM, P < 0.001, respectively), as well as elevated serum sCD14 (2245 ± 75.1 vs. 1834 ± 45.8 ng/mL, P < 0.0001) and sCD163 levels (457.3 ± 31.8 vs. 326.8 ± 20.7 ng/mL, P = 0.001), compared with healthy controls at baseline. Furthermore, a modified small molecule metabolomic and lipidomic signature was observed in patients with CSA and ACS compared with healthy controls. These findings provide evidence of a link between gut microbiome composition and gut bacterial metabolites with CVD. Future time course studies in patients to observe temporal changes and subsequent associations with gut microbiome composition are required to provide insight into how these are affected by transient changes following an acute coronary event.NEW & NOTEWORTHY The study found discriminative microorganisms differentiating patients with acute coronary syndrome (ACS) from healthy controls. In addition, reduced levels of certain bacterial metabolites and elevated sCD14 and sCD163 were observed in patients with ACS compared with healthy controls. Furthermore, modified small molecule metabolomic and lipidomic signatures were found in both patient groups. Although it is not known whether these differences in profiles are associated with disease development and/or progression, the findings provide exciting options for potential new disease-related mechanism(s) and associated therapeutic target(s).

Outcomes of drug-coated balloon angioplasty in patients with dyslipidemia in the BIOLUX P-III registry: A subgroup analysis.

OBJECTIVES: The aim of this study was to assess the mid-term outcomes of the use of drug-coated balloons (DCBs) to treat infrainguinal peripheral arterial disease (PAD) in patients with dyslipidemia. METHODS: BIOLUX P-III is a prospective, international, multicenter, all-comers registry-based study that was conducted at 44 sites with follow-ups at 6, 12 and 24 months. The present study is a subgroup analysis comparing the outcomes associated with endovascular revascularization with those associated with Passeo-18 lux DCBs in patients with and without dyslipidemia. The proportions of patients free from major adverse events (defined as device- or procedure-related mortality within 30 days, clinically driven target lesion revascularization (CD-TLR) and major target limb amputation), target vessel revascularization, and patient-reported outcomes within 24 months postintervention were compared between the two groups. RESULTS: A total of 876 patients with symptomatic PAD who underwent peripheral revascularization with DCBs and had information on their dyslipidemia status were included; 588 of those patients had dyslipidemia. There was no difference in the proportion of patients free from MAEs between the groups. The percentages of patients who were 6, 12 and 24 months free from CD-TLR were significantly lower in the dyslipidemia group than in the nondyslipidemia group (86.3% vs 91.9% at 2 years, p = .0183). Similarly, the percentage of patients free from target vessel revascularization was lower in the dyslipidemia group at all timepoints (83.3% vs 89.3% at 2 years, p = .0203). There was no difference in mortality or major or minor limb amputation rates. Other secondary outcomes were similar between the groups. CONCLUSIONS: Compared to those without dyslipidemia, patients with symptomatic PAD and dyslipidemia who underwent revascularization with a Passeo-18 lux DCB had greater rates of CD-TLR and TVR. However, having dyslipidemia did not increase the risk of mortality or limb amputation. CLINICAL TRIAL REGISTRATION: NCT02276313.

Evaluative judgement in practice education: How does the ability to judge the quality of work impact placement performance?

INTRODUCTION: Occupational therapy students need to be ready to work autonomously in a range of environments as soon as they complete their degree. Practice education experiences are considered key to students developing the competencies that autonomous work requires. To function autonomously in practice environments, it is argued that practitioners need to be able to judge the quality of their own work and the work of others. This is referred to as evaluative judgement. However, there is limited empirical literature relating to evaluative judgement and even less exploring the concept within occupational therapy. METHODS: This study used qualitative methods, seeking to understand the evaluative judgements of clinical practice made by third- and fourth-year occupational therapy students during practice education. RESULTS: Twenty-one interviews were conducted with third- (n = 10) and fourth-year occupational therapy students (n = 1), university support staff supporting practice education (n = 4), and practice education supervisors (n = 5) at one Australian university. Practice education grades and documentation were also used as data. Data were analysed thematically, and two themes, each with three sub-themes, were identified: students coming to understand expected standards, with the following sub-themes: students attuning to cues, cues that inform supervisors about students' meeting the standards, and barriers and frustrations to understanding standards; and practising and developing evaluative judgement, with the following sub-themes: making comparisons, acting on feedback, and reflective practice. CONCLUSIONS: Practice education experiences provide many context-specific opportunities for students to develop their evaluative judgement. Students may be supported to come to know what quality work looks like by offering scaffolded opportunities to develop evaluative judgement in university and practice education settings.

Insights into the associations between the gut microbiome, its metabolites, and heart failure.

Heart failure (HF) is the end stage of most cardiovascular diseases and remains a significant health problem globally. We aimed to assess whether patients with left ventricular ejection fraction ≤45% had alterations in both the gut microbiome profile and production of associated metabolites when compared with a healthy cohort. We also examined the associated inflammatory, metabolomic, and lipidomic profiles of patients with HF. This single center, observational study, recruited 73 patients with HF and 59 healthy volunteers. Blood and stool samples were collected at baseline and 6-mo follow-up, along with anthropometric and clinical data. When compared with healthy controls, patients with HF had reduced gut bacterial alpha diversity at follow-up (P = 0.004) but not at baseline. The stool microbiota of patients with HF was characterized by a depletion of operational taxonomic units representing commensal Clostridia at both baseline and follow-up. Patients with HF also had significantly elevated baseline plasma acetate (P = 0.007), plasma trimethylamine-N-oxide (TMAO) (P = 0.003), serum soluble CD14 (sCD14; P = 0.005), and soluble CD163 (sCD163; P = 0.004) levels compared with healthy controls. Furthermore, patients with HF had a distinct metabolomic and lipidomic profile at baseline when compared with healthy controls. Differences in the composition of the gut microbiome and the levels of associated metabolites were observed in patients with HF when compared with a healthy cohort. This was also associated with an altered metabolomic and lipidomic profile. Our study identifies microorganisms and metabolites that could represent new therapeutic targets and diagnostic tools in the pathogenesis of HF.NEW & NOTEWORTHY We found a reduction in gut bacterial alpha diversity in patients with heart failure (HF) and that the stool microbiota of patients with HF was characterized by depletion of operational taxonomic units representing commensal Clostridia at both baseline and follow-up. Patients with HF also had altered bacterial metabolites and increased inflammatory profiles compared with healthy controls. A distinct metabolomic and lipidomic profile was present in patients with HF at baseline when compared with healthy controls.

Anti-inflammatory effect of biologic therapy in patients with psoriatic disease: A prospective cohort FDG PET study.

AIM: The aim of the study was to evaluate the changes in central vascular inflammation measured by FDG PET and myocardial blood flow reserve (MFR) determined by 82Rb PET following therapy with biologic agents for 6 months in patients with psoriatic arthritis (PsA) and/or cutaneous psoriasis (PsO) (group 1) and compare with PsO subjects receiving non-biologic therapy (group 2) and controls (group 3). METHODS AND RESULTS: Target-to-background ratio (TBR) by FDG PET in the most diseased segment of the ascending aorta (TBRmax) was measured to assess vascular inflammation. 82Rb PET studies were used to assess changes in left ventricular MFR. A total of 34 participants were enrolled in the study (11 in group 1, 13 in group 2, and 10 controls). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (ΔTBRmax: - .46 ± .55) compared to the PsO group treated with non-biologic therapy (ΔTBRmax: .23 ± .67). Those showing response to biologic agents maintained MFR compared to who showed no response. CONCLUSION: In a cohort of psoriasis patients treated with biologics, FDG uptake in the thoracic aorta decreased over the study period. Patients who demonstrated a significant anti-inflammatory response on FDG PET imaging maintained their MFR compared to non-responders.

Long-term dietary nitrate supplementation slows the progression of established atherosclerosis in ApoE-/- mice fed a high fat diet.

BACKGROUND AND AIMS: Atherosclerosis is associated with a reduction in the bioavailability and/or bioactivity of endogenous nitric oxide (NO). Dietary nitrate has been proposed as an alternate source when endogenous NO production is reduced. Our previous study demonstrated a protective effect of dietary nitrate on the development of atherosclerosis in the apoE-/- mouse model. However most patients do not present clinically until well after the disease is established. The aims of this study were to determine whether chronic dietary nitrate supplementation can prevent or reverse the progression of atherosclerosis after disease is already established, as well as to explore the underlying mechanism of these cardiovascular protective effects. METHODS: 60 apoE-/- mice were given a high fat diet (HFD) for 12 weeks to allow for the development of atherosclerosis. The mice were then randomized to (i) control group (HFD + 1 mmol/kg/day NaCl), (ii) moderate-dose group (HFD +1 mmol/kg/day NaNO3), or (iii) high-dose group (HFD + 10 mmol/kg/day NaNO3) (20/group) for a further 12 weeks. A group of apoE-/- mice (n = 20) consumed a normal laboratory chow diet for 24 weeks and were included as a reference group. RESULTS: Long-term supplementation with high dose nitrate resulted in ~ 50% reduction in plaque lesion area. Collagen expression and smooth muscle accumulation were increased, and lipid deposition and macrophage accumulation were reduced within atherosclerotic plaques of mice supplemented with high dose nitrate. These changes were associated with an increase in nitrite reductase as well as activation of the endogenous eNOS-NO pathway. CONCLUSION: Long-term high dose nitrate significantly attenuated the progression of established atherosclerosis in the apoE-/- mice fed a HFD. This appears to be mediated in part through a XOR-dependent reduction of nitrate to NO, as well as enhanced eNOS activation via increased Akt and eNOS phosphorylation.

Meaning making about performance: A comparison of two specialty feedback cultures.

INTRODUCTION: Specialty trainees often struggle to understand how well they are performing, and feedback is commonly seen as a solution to this problem. However, medical education tends to approach feedback as acontextual rather than located in a specialty-specific cultural world. This study therefore compares how specialty trainees in surgery and intensive care medicine (ICM) make meaning about the quality of their performance and the role of feedback conversations in this process. METHODS: We conducted a qualitative interview study in the constructivist grounded theory tradition. We interviewed 17 trainees from across Australia in 2020, eight from ICM and nine from surgery, and iterated between data collection and analytic discussions. We employed open, focused, axial and theoretical coding. FINDINGS: There were significant divergences between specialties. Surgical trainees had more opportunity to work directly with supervisors, and there was a strong link between patient outcome and quality of care, with a focus on performance information about operative skills. ICM was a highly uncertain practice environment, where patient outcome could not be relied upon as a source of performance information; valued performance information was diffuse and included tacit emotional support. These different 'specialty feedback cultures' strongly influenced how trainees orchestrated opportunities for feedback, made meaning of their performance in their day-to-day patient care tasks and 'patched together' experiences and inputs into an evolving sense of overall progress. DISCUSSION: We identified two types of meaning-making about performance: first, trainees' understanding of an immediate performance in a patient-care task and, second, a 'patched together' sense of overall progress from incomplete performance information. This study suggests approaches to feedback should attend to both, but also take account of the cultural worlds of specialty practice, with their attendant complexities. In particular, feedback conversations could better acknowledge the variable quality of performance information and specialty specific levels of uncertainty.

A sex-based analysis of 5-year outcomes following stenting for the treatment of aorto-iliac occlusive disease.

OBJECTIVES: The aim of this study was to evaluate the impact of sex on mid-term outcomes following stenting for aorto-iliac occlusive disease (AIOD). METHODS: The Covered versus Balloon Expandable Stent Trial (COBEST) compared the safety and efficacy of the covered stent (CS) with those of the bare metal stent (BMS) in the treatment of hemodynamically significant AIOD. It was identified that CS provided a significant benefit. The primary endpoint of our analysis was the rate of primary patency 5 years following stenting for AIOD (inclusive of both CS and BMS) in both sexes. RESULTS: Of the 168 lesions treated, 103 (61%) were present in men and 65 (39%) were present in women. Of the concomitant comorbidities, diabetes mellitus was significantly more common in women (17.5% vs 41.5%, p = .006). Although chronic limb threatening ischemia (CLTI) at the time of intervention was more common in women, the difference was not significant (16.5% vs 24.6%, p = .395). Sex was not associated with the primary patency rate (male; 0.70, 95% confidence interval [CI]: 0.23-2.19, p = .543). When considering both male sex and the utilization of BMS, no significant impact was found on the primary patency rate (hazard ratio [HR]: 3.43, 95% CI: 0.69-17.10, p = .133). All-cause mortality at 60 months was 22.6% in men compared to 19.4% in women (p = .695). CONCLUSIONS: No significant difference was identified in the primary patency rate between the sexes. Further investigation is warranted to ascertain whether sex-specific interventional guidelines are required in this regard.

Molecular Mechanisms of AMPA Receptor Trafficking in the Nervous System.

Synaptic plasticity enhances or reduces connections between neurons, affecting learning and memory. Postsynaptic AMPARs mediate greater than 90% of the rapid excitatory synaptic transmission in glutamatergic neurons. The number and subunit composition of AMPARs are fundamental to synaptic plasticity and the formation of entire neural networks. Accordingly, the insertion and functionalization of AMPARs at the postsynaptic membrane have become a core issue related to neural circuit formation and information processing in the central nervous system. In this review, we summarize current knowledge regarding the related mechanisms of AMPAR expression and trafficking. The proteins related to AMPAR trafficking are discussed in detail, including vesicle-related proteins, cytoskeletal proteins, synaptic proteins, and protein kinases. Furthermore, significant emphasis was placed on the pivotal role of the actin cytoskeleton, which spans throughout the entire transport process in AMPAR transport, indicating that the actin cytoskeleton may serve as a fundamental basis for AMPAR trafficking. Additionally, we summarize the proteases involved in AMPAR post-translational modifications. Moreover, we provide an overview of AMPAR transport and localization to the postsynaptic membrane. Understanding the assembly, trafficking, and dynamic synaptic expression mechanisms of AMPAR may provide valuable insights into the cognitive decline associated with neurodegenerative diseases.

Australian Atherosclerosis Society Position Statement on Lipoprotein(a): Clinical and Implementation Recommendations.

This position statement provides guidance to cardiologists and related specialists on the management of adult patients with elevated lipoprotein(a) [Lp(a)]. Elevated Lp(a) is an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). While circulating Lp(a) levels are largely determined by ancestry, they are also influenced by ethnicity, hormones, renal function, and acute inflammatory events, such that measurement should be done after accounting for these factors. Further, circulating Lp(a) concentrations should be estimated using an apo(a)-isoform independent assay that employs appropriate calibrators and reports the results in molar units (nmol/L). Selective screening strategies of high-risk patients are recommended, but universal screening of the population is currently not advised. Testing for elevated Lp(a) is recommended in all patients with premature ASCVD and those considered to be at intermediate-to-high risk of ASCVD. Elevated Lp(a) should be employed to assess and stratify risk and to enable a decision on initiation or intensification of preventative treatments, such as cholesterol lowering therapy. In adult patients with elevated Lp(a) at intermediate-to-high risk of ASCVD, absolute risk should be reduced by addressing all modifiable behavioural, lifestyle, psychosocial and clinical risk factors, including maximising cholesterol-lowering with statin and ezetimibe and, where appropriate, PCSK9 inhibitors. Apheresis should be considered in patients with progressive ASCVD. New ribonucleic acid (RNA)-based therapies which directly lower Lp(a) are undergoing clinical trials.

Anti-inflammatory effect of rosuvastatin in patients with HIV infection: An FDG-PET pilot study.

AIMS: This study aimed to evaluate markers of systemic as well as imaging markers of inflammation in the ascending aorta, bone marrow, and spleen measured by 18F-FDG PET/CT, in HIV+ patients at baseline and following therapy with rosuvastatin. METHODS AND RESULTS: Of the 35 HIV+ patients enrolled, 17 were randomized to treatment with 10 mg/day rosuvastatin and 18 to usual care for 6 months. An HIV- control cohort was selected for baseline comparison of serum inflammatory markers and monocyte markers of inflammation. 18F-FDG-PET/CT imaging of bone marrow, spleen, and thoracic aorta was performed in the HIV+ cohort at baseline and 6 months. While CD14++CD16- and CCR2 expressions were reduced, serum levels of IL-7, IL-8, and MCP-1 were elevated in the HIV+ population compared to the controls. There was a significant drop in FDG uptake in the bone marrow (TBRmax), spleen (SUVmax) and thoracic aortic (TBRmax) in the statin-treated group compared to the control group (bone marrow: - 10.3 ± 16.9% versus 5.0 ± 18.9%, p = .0262; spleen: - 9.8 ± 20.3% versus 11.3 ± 28.8%, p = .0497; thoracic aorta: - 19.1 ± 24.2% versus 4.3 ± 15.4%, p = .003). CONCLUSIONS: HIV+ patients had significantly markers of systemic inflammation including monocyte activation. Treatment with low-dose rosuvastatin in the HIV+ cohort significantly reduced bone marrow, spleen and thoracic aortic FDG uptake.

Beneficial effects of inorganic nitrate in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic representation of the metabolic disorders. Inorganic nitrate/nitrite can be converted to nitric oxide, regulate glucose metabolism, lower lipid levels, and reduce inflammation, thus raising the hypothesis that inorganic nitrate/nitrite could be beneficial for improving NAFLD. This study assessed the therapeutic effects of chronic dietary nitrate on NAFLD in a mouse model. 60 ApoE-/- mice were fed a high-fat diet (HFD) for 12 weeks to allow for the development of atherosclerosis with associated NAFLD. The mice were then randomly assigned to different groups (20/group) for a further 12 weeks: (i) HFD + NaCl (1 mmol/kg/day), (ii) HFD + NaNO3 (1 mmol/kg/day), and (iii) HFD + NaNO3 (10 mmol/kg/day). A fourth group of ApoE-/- mice consumed a normal chow diet for the duration of the study. At the end of the treatment, caecum contents, serum, and liver were collected. Consumption of the HFD resulted in significantly greater lipid accumulation in the liver compared to mice on the normal chow diet. Mice whose HFD was supplemented with dietary nitrate for the second half of the study, showed an attenuation in hepatic lipid accumulation. This was also associated with an increase in hepatic AMPK activity compared to mice on the HFD. In addition, a significant difference in bile acid profile was detected between mice on the HFD and those receiving the high dose nitrate supplemented HFD. In conclusion, dietary nitrate attenuates the progression of liver steatosis in ApoE-/- mice fed a HFD.

Statin Toxicity.

There is now overwhelming evidence to support lowering LDL-c (low-density lipoprotein cholesterol) to reduce cardiovascular morbidity and mortality. Statins are a class of drugs frequently prescribed to lower cholesterol. However, in spite of their wide-spread use, discontinuation and nonadherence remains a major gap in both the primary and secondary prevention of atherosclerotic cardiovascular disease. The major reason for statin discontinuation is because of the development of statin-associated muscle symptoms, but a range of other statin-induced side effects also exist. Although the mechanisms behind these side effects have not been fully elucidated, there is an urgent need to identify those at increased risk of developing side effects as well as provide alternative treatment strategies. In this article, we review the mechanisms and clinical importance of statin toxicity and focus on the evaluation and management of statin-associated muscle symptoms.

Lipoprotein (a) and Hypertension.

PURPOSE OF REVIEW: To provide an overview of the associations between elevated blood pressure and lipoprotein (a) and possible causal links, as well as data on the prevalence of elevated lipoprotein (a) in a cohort of hypertensive patients. RECENT FINDINGS: Elevated lipoprotein (a) is now considered to be an independent and causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve disease. Despite this, there are limited data demonstrating an association between elevated lipoprotein (a) and hypertension. Further, there is limited mechanistic data linking lipoprotein (a) and hypertension through either renal impairment or direct effects on the vasculature. Despite the links between lipoprotein (a) and atherosclerosis, there are limited data demonstrating an association with hypertension. Evidence from our clinic suggests that ~ 30% of the patients in this at-risk, hypertensive cohort had elevated lipoprotein (a) levels and that measurement of lipoprotein (a) maybe useful in risk stratification.

Flaxseed Supplementation Reduces Plasma Lipoprotein(a) Levels: A Meta-Analysis.

CONTEXT: Elevated levels of lipoprotein (a) [Lp(a)] are an independent risk factor for premature cardiovascular disease (CVD). Flaxseed (Linum usitiatissimum L.) is a rich source of alpha-linolenic acid, phytoestrogens, and lignans and has been shown to improve several cardiovascular risk factors, although the overall effect on Lp(a) is unknown. OBJECTIVE: The study intended to assess the impact of flaxseed on plasma Lp(a) levels through a meta-analysis of the results of randomized controlled trials (RCTs). DESIGN: PubMed-Medline, Scopus, Embase, and Google Scholar databases were searched using the following search terms in titles and abstracts: flaxseed OR Linum usitatissimum OR lignin OR linseed AND lipoprotein(a) OR lipoprotein (a) OR Lp(a) OR Lp (a). RESULTS: Of the 48 RCTs, 6 were eligible for inclusion, and the results suggested a significant decrease in plasma Lp(a) levels-standardized mean difference: -0.22, 95% confidence interval: -0.41 to -0.04, P = .017-following supplementation with flaxseed-containing products. CONCLUSIONS: This finding highlights the potential clinical significance of flaxseed supplementation for patients who are at risk of a high residual CVD despite intensive statin therapy, patients with hyperliporoteinemia(a), and patients who prefer natural remedies for CVD prevention in the context of a healthy lifestyle. Further RCTs are needed to establish the role of flaxseed-containing products on lowering Lp(a).

Extrinsic and Intrinsic Responses in the Development and Progression of Atherosclerosis.

Atherosclerosis is a multifactorial disease that is thought to be primarily inflammatory in origin. Given the contribution of inflammation to the development and progression of atherosclerosis, other conditions that are characterised by a dysregulated inflammatory response have also been proposed to play a role. The purpose of this review is to organise and present the various inflammatory processes that can affect atherosclerosis into two broad categories: extrinsic or host-independent and intrinsic or host-dependent. Within these two categories, we will discuss various processes that may contribute to the development and progression of atherosclerosis and the clinical studies describing these associations. Although the clinical trials investigating anti-inflammatory therapies have to date provided mixed results, further studies, particularly in conjunction with lipid-lowering and blood pressure lowering therapies should be considered.

Mechanisms of the protective effects of nitrate and nitrite in cardiovascular and metabolic diseases.

Within the body, NO is produced by nitric oxide synthases via converting l-arginine to citrulline. Additionally, NO is also produced via the NOS-independent nitrate-nitrite-NO pathway. Unlike the classical pathway, the nitrate-nitrite-NO pathway is oxygen independent and viewed as a back-up function to ensure NO generation during ischaemia/hypoxia. Dietary nitrate and nitrite have emerged as substrates for endogenous NO generation and other bioactive nitrogen oxides with promising protective effects on cardiovascular and metabolic function. In brief, inorganic nitrate and nitrite can decrease blood pressure, protect against ischaemia-reperfusion injury, enhance endothelial function, inhibit platelet aggregation, modulate mitochondrial function and improve features of the metabolic syndrome. However, many questions regarding the specific mechanisms of these protective effects on cardiovascular and metabolic diseases remain unclear. In this review, we focus on nitrate/nitrite bioactivation, as well as the potential mechanisms for nitrate/nitrite-mediated effects on cardiovascular and metabolic diseases. Understanding how dietary nitrate and nitrite induce beneficial effect on cardiovascular and metabolic diseases could open up novel therapeutic opportunities in clinical practice.

Enzymatically modified isoquercitrin improves endothelial function in volunteers at risk of cardiovascular disease.

A higher intake of food rich in flavonoids such as quercetin can reduce the risk of CVD. Enzymatically modified isoquercitrin (EMIQ®) has a bioavailability 17-fold higher than quercetin aglycone and has shown potential CVD moderating effects in animal studies. The present study aimed to determine whether acute ingestion of EMIQ® improves endothelial function, blood pressure (BP) and cognitive function in human volunteers at risk of CVD. Twenty-five participants (twelve males and thirteen females) with at least one CVD risk factor completed this randomised, controlled, crossover study. In a random order, participants were given EMIQ® (2 mg aglycone equivalent)/kg body weight or placebo alongside a standard breakfast meal. Endothelial function, assessed by flow-mediated dilatation (FMD) of the brachial artery was measured before and 1·5 h after intervention. BP, arterial stiffness, cognitive function, BP during cognitive stress and measures of quercetin metabolites, oxidative stress and markers of nitric oxide (NO) production were assessed post-intervention. After adjustment for pre-treatment measurements and treatment order, EMIQ® treatment resulted in a significantly higher FMD response compared with the placebo (1·80 (95 % CI 0·23, 3·37) %; P = 0·025). Plasma concentrations of quercetin metabolites were significantly higher (P < 0·001) after EMIQ® treatment compared with the placebo. No changes in BP, arterial stiffness, cognitive function or biochemical parameters were observed. In this human intervention study, the acute administration of EMIQ® significantly increased circulating quercetin metabolites and improved endothelial function. Further clinical trials are required to assess whether health benefits are associated with long-term EMIQ® consumption.

Family Perspectives on Visiting the Pediatric Emergency Department for Migraine: A Qualitative Study.

OBJECTIVE: The aim of this study was to explore the perspectives of families regarding their expectations and experience of visiting the emergency department (ED) for migraine. METHODS: This was a qualitative study involving the families of 25 patients aged 10 to 18 years receiving ED care for acute migraine. Following their visit, independent semistructured telephone interviews were conducted with both the patient and parent or guardian. Questions were designed to explore factors pertaining to the family's perspective regarding their visit to the ED and expectations for the ED visit. RESULTS: Families reported a variety of reasons for visiting the ED. The majority of participants reported that they were worried about their headaches. Families more commonly had expectations for treatment than they did for investigations. As compared with patients, parents more commonly reported specific expectations for investigations and less commonly expressed concerns about intravenous treatments. Expectations for treatment efficacy varied: whereas some parents expected complete pain relief, for others, lesser degrees of relief were considered satisfactory. The experience of treatment efficacy was related to willingness to receive the same treatment again. CONCLUSIONS: Given that a high frequency of families endorsed that they were worried about the headache when presenting to the ED, clinicians should strive to make a diagnosis of migraine in the ED setting and to educate families about this diagnosis. Because of divergent parent and patient perspectives, health care providers should inquire about family expectations, especially in relation to expectations for investigations and concerns surrounding intravenous interventions, and ensure that both the patient's and parent's perspectives are considered when developing a management plan for pediatric migraine.

Lipid management in people with peripheral artery disease.

PURPOSE OF REVIEW: To summarize recent data on the role of dyslipidaemia and the benefit from managing this in people with disease of the abdominal aorta and its peripheral branches (peripheral artery disease, PAD). RECENT FINDINGS: Findings from the Further Cardiovascular Outcomes Research with Proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibition in Subjects with Elevated Risk (FOURIER) trial demonstrate the benefit of intensely lowering low-density lipoprotein-cholesterol (LDL-c) in people with PAD to substantially reduce the incidence of major cardiovascular events (MACE; myocardial infarction, stroke or cardiovascular death) and major adverse limb events (MALE). Despite the evidence of substantial benefits from lowering LDL-c, the uptake of drug therapies to lower LDL-c remains sub-optimal in people with PAD. SUMMARY: Effective methods to educate physicians and patients on best medical management are needed. Further research is needed to examine the benefit of LDL-c lowering and other lipid therapies for PAD-specific problems like abdominal aortic aneurysm progression and walking impairment. Other novel lipid therapies, such as those that lower lipoprotein (a), maybe particularly beneficial to people with PAD given the evidence indicating high concentrations in this population and the high incidence of MACE in these individuals.