Cardiovascular risk in a contemporary cohort of patients with myeloproliferative neoplasms'.

BACKGROUND: Myeloproliferative neoplasms (MPNs) are a group of disorders of clonal haemopoiesis associated with an inherent risk of arterial and venous thrombotic complications. The prevalence of thrombotic complications and the impact of cardiovascular risk factors (CVRFs) in contemporary patient cohorts within the current era of MPN treatments have not been completely defined. OBJECTIVES: We aim to characterise the cardiovascular risk of patients with MPN by identifying the prevalence of CVRFs and describing the pattern of thrombotic events. We also aim to utilise the QRISK3 algorithm, which is a validated model used to estimate an individual's risk of developing cardiovascular disease, to further phenotype this cohort of patients. METHODS: We perform a retrospective analysis on a single-centre cohort of 438 patients with MPN. RESULTS: MPN patients continue to carry a high burden of vascular morbidity with a prevalence of arterial thrombotic events in 15.8 % (69/438) and venous thrombotic events in 13.2 % (58/438) of the cohort. The novel use of the QRISK3 algorithm, which showed a mean score of 13.7 % across the MPN population, provides further evidence to suggest an increased cardiovascular risk in MPN patients. CONCLUSION: With an increased risk of cardiovascular disease in patients with MPN, we propose an integrated approach between primary and specialised healthcare services using risk stratification tools such as QRISK3, which will allow aggressive optimisation of CVRFs to prevent thrombosis and reduce the overall morbidity and mortality in patients with MPN.

What proportion of people have a follow-up biopsy in randomized trials of treatments for non-alcoholic steatohepatitis?: A systematic review and meta-analysis.

BACKGROUND AND AIM: Trials of treatments for non-alcoholic steatohepatitis require endpoint assessment with liver biopsies. Previous large-scale trials have calculated their sample size expecting high retention but on average did not achieve this. We aimed to quantify the proportion of participants with a valid follow-up biopsy. METHODS: We conducted a systematic review of MEDLINE and Embase until May 2020 and included randomized clinical trials of any intervention in non-alcoholic steatohepatitis with at least 1-year follow-up. We were guided by Cochrane methods to run a meta-analysis with generalized linear mixed models with random effects. RESULTS: Forty-one trials (n = 6,695) were included. The proportion of participants with a valid follow-up biopsy was 82% (95%CI: 78%-86%, I2 = 92%). There was no evidence of a difference by location, trial length, or by allocated treatment group. Reasons for missing follow-up biopsies were, in ranked order, related to participants (95 per 1,000 participants (95%CI: 69-129, I2 = 92%), medical factors, protocol, trial conduct, and other/unclear. Biopsy-related serious adverse events occurred in 16 per 1,000 participants (95% CI: 8-33, I2 = 54%). No biopsy-related deaths were reported. CONCLUSIONS: The proportion of participants with a valid follow-up biopsy in therapeutic trials in non-alcoholic steatohepatitis is on average 82%, with around 1 in 10 participants declining a follow-up biopsy. These findings can inform adequately-powered trials.

The effect of the magnitude of weight loss on non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND: Trials show that weight loss interventions improve biomarkers of non-alcoholic fatty liver disease (NAFLD), but it is unclear if a dose-response relationship exists. OBJECTIVE: We aimed to quantify the dose-response relationship between the magnitude of weight loss and improvements in NAFLD. METHODS: Nine databases and trial registries were searched until October 2020. Single-arm, non-randomized comparative, or randomized trials of weight loss interventions (behavioral weight loss programs [BWLPs], pharmacotherapy, or bariatric surgery) in people with NAFLD were eligible for inclusion if they reported an association between changes in weight and changes in blood, radiological, or histological biomarkers of liver disease. The review followed Cochrane methods and the risk of bias was assessed using the Newcastle-Ottawa scale. Pooled unstandardized b coefficients were calculated using random-effect meta-analyses. RESULTS: Forty-three studies (BWMPs: 26, pharmacotherapy: 9, surgery: 8) with 2809 participants were included. The median follow-up was 6 (interquartile range: 6) months. The direction of effect was generally consistent but the estimates imprecise. Every 1 kg of weight lost was associated with a 0.83-unit (95% CI: 0.53 to 1.14, p < 0.0001, I2 = 92%, n = 18) reduction in alanine aminotransferase (U/L), a 0.56-unit (95% CI: 0.32 to 0.79, p < 0.0001, I2 = 68%, n = 11) reduction in aspartate transaminase (U/L), and a 0.77 percentage point (95% CI: 0.51 to 1.03, p < 0.0001, I2 = 72%, n = 11) reduction in steatosis assessed by radiology or histology. There was evidence of a dose-response relationship with liver inflammation, ballooning, and resolution of NAFLD or NASH, but limited evidence of a dose-response relationship with fibrosis or NAFLD activity score. On average, the risk of bias for selection and outcome was medium and low, respectively. CONCLUSION: Clinically significant improvements in NAFLD are achieved even with modest weight loss, but greater weight loss is associated with greater improvements. Embedding support for formal weight loss programs as part of the care pathway for the treatment of NAFLD could reduce the burden of disease. PROSPERO: CRD42018093676.

Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI.

Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects culminating in congestive heart failure (HF). There are currently no clinical imaging techniques or biomarkers available to detect DOX-cardiotoxicity before functional decline. Mitochondrial dysfunction is thought to be a key factor driving functional decline, though real-time metabolic fluxes have never been assessed in DOX-cardiotoxicity. Hyperpolarized magnetic resonance imaging (MRI) can assess real-time metabolic fluxes in vivo. Here we show that cardiac functional decline in a clinically relevant rat-model of DOX-HF is preceded by a change in oxidative mitochondrial carbohydrate metabolism, measured by hyperpolarized MRI. The decreased metabolic fluxes were predominantly due to mitochondrial loss and additional mitochondrial dysfunction, and not, as widely assumed hitherto, to oxidative stress. Since hyperpolarized MRI has been successfully translated into clinical trials this opens up the potential to test cancer patients receiving DOX for early signs of cardiotoxicity.

Cardiac applications of hyperpolarised magnetic resonance.

Cardiovascular disease is the leading cause of death world-wide. It is increasingly recognised that cardiac pathologies show, or may even be caused by, changes in metabolism, leading to impaired cardiac energetics. The heart turns over 15 times its own weight in ATP every day and thus relies heavily on the availability of substrates and on efficient oxidation to generate this ATP. A number of old and emerging drugs that target different aspects of metabolism are showing promising results with regard to improved cardiac outcomes in patients. A non-invasive imaging technique that could assess the role of different aspects of metabolism in heart disease, as well as measure changes in cardiac energetics due to treatment, would be valuable in the routine clinical care of cardiac patients. Hyperpolarised magnetic resonance spectroscopy and imaging have revolutionised metabolic imaging, allowing real-time metabolic flux assessment in vivo for the first time. In this review we summarise metabolism in the healthy and diseased heart, give an introduction to the hyperpolarisation technique, 'dynamic nuclear polarisation' (DNP), and review the preclinical studies that have thus far explored healthy cardiac metabolism and different models of human heart disease. We furthermore show what advances have been made to translate this technique into the clinic, what technical challenges still remain and what unmet clinical needs and unexplored metabolic substrates still need to be assessed by researchers in this exciting and fast-moving field.

Illicit drugs and surgery.

Depending on their pharmacology and the ways they are used, illicit drugs can lead to a wide range of medical and surgical problems. The drug-using patient requiring surgery or pain relief needs special attention in order to avoid interactions and complications, especially as most of these patients will be using more than one drug. In order to raise awareness, we review the different drugs, their clinical effects and the problems which may be encountered.

Cost-effectiveness of screening and referral to an alcohol health worker in alcohol misusing patients attending an accident and emergency department: a decision-making approach.

We present the cost and cost-effectiveness of referral to an alcohol health worker (AHW) and information only control in alcohol misusing patients. The study was a pragmatic randomised controlled trial conducted from April 2001 to March 2003 in an accident and emergency department (AED) in a general hospital in London, England. A total of 599 adults identified as drinking hazardously according to the Paddington Alcohol Test were randomised to referral to an alcohol health worker who delivered a brief intervention (n = 287) or to an information only control (n = 312). Total societal costs, including health and social services costs, criminal justice costs and productivity losses, and clinical measures of alcohol consumption were measured. Levels of drinking were observably lower in those referred to an AHW at 12 months follow-up and statistically significantly lower at 6 months follow-up. Total costs were not significantly different at either follow-up. Referral to AHWs in an AED produces favourable clinical outcomes and does not generate a significant increase in cost. A decision-making approach revealed that there is at least a 65% probability that referral to an AHW is more cost-effective than the information only control in reducing alcohol consumption among AED attendees with a hazardous level of drinking.

Cannabis as a precipitant of cardiovascular emergencies.

Cannabis smoking is on the increase both in the United Kingdom and in the United States. For over three decades it has been known that cannabis has pathophysiological effects on the cardiovascular system, and previously an association with an increased risk of myocardial infarction has been reported. However, it is not yet known whether cannabis contributes directly to coronary artery disease. We describe two distinct cases; in the first cannabis use precipitated a malignant arrhythmia in a patient with critical ischaemia from longstanding coronary artery disease. In the second, a young patient presented with an acute myocardial infarction that had started whilst smoking marijuana; subsequently diffuse coronary artery disease was found at angiography despite the patient's low risk factor status. Patients who are known cannabis smokers and who have cardiovascular disease should be warned that it is likely to aggravate coronary ischaemia, and may even trigger myocardial infarction.