Leanne Harling

Body Mass Index Category as a Risk Factor for Colorectal Adenomas: A Systematic Review and Meta-Analysis

OBJECTIVES:The association between increasing body weight and colorectal adenoma prevalence has been suggested to follow a similar pattern to excess weight and colorectal cancer, although the magnitude of this relationship has not been validated. The objective of this study was to quantify the association and dose–response relationship between body mass index (BMI) and colorectal adenoma prevalence in clinical trials.METHODS:We systematically reviewed 23 studies (168,201 participants), which compared the prevalence of colorectal adenomas according to World Health Organization BMI categories. We assessed the effects of each BMI category on colorectal adenomas where odds ratio (OR) was used as a surrogate for effect size, and applied multivariate meta-analysis as a method of sensitivity analysis to evaluate the robustness of our findings and to analyze adenoma prevalence by multiple BMI categories simultaneously to assess for a dose–response relationship. Heterogeneity and publication bias were assessed.RESULTS:Subjects with a BMI of ≥25 had a significantly higher prevalence of colorectal adenomas (OR=1.24 (95% confidence interval (CI): 1.16–1.33), P<0.01) when compared with those with BMI<25. Multivariate meta-analysis also confirmed a positive association between higher BMI categories and the prevalence of colorectal adenoma (BMI: 25–30 vs. BMI<25; OR=1.21 (95% CI: 1.07–1.38), P<0.01; BMI≥30 vs. BMI<25; OR=1.32 (95% CI: 1.18–1.48), P<0.01) and revealed a dose–response relationship.CONCLUSIONS:The positive association between obesity and colorectal adenoma prevalence demonstrates an underlying dose–response relationship according to BMI. Colorectal centers may benefit from the timely screening of obese patients for colorectal adenomas in addition to clarifying the biological role of adiposity on colorectal tumor initiation and progression.

Do antioxidant vitamins have an anti-arrhythmic effect following cardiac surgery? A meta-analysis of randomised controlled trials

Background Postoperative atrial fibrillation (POAF) affects approximately 30% of patients undergoing elective cardiac surgery. While its pathogenesis is multifactorial, increasing evidence supports a role for oxidative stress in the electrophysiological remodelling associated with AF. Although prophylactic antioxidants appear to be a potentially attractive pharmacotherapy, there is still uncertainty regarding their efficacy. This study aims to provide a quantitative summary of the current evidence surrounding antioxidant vitamins and POAF prevention. Methods A systematic literature review identified five randomised controlled trials incorporating 567 patients (n=284 antioxidant, n=283 control). These were meta-analysed using random effects modelling. Heterogeneity, subgroup analysis, quality scoring and risk of bias were assessed. Primary endpoints were the incidence of POAF and all-cause arrhythmia. Secondary endpoints were length of stay in the intensive care unit (ITU) and length of hospital stay. Results Vitamins C and E significantly reduced the incidence of POAF (OR 0.43, 95% CI 0.21 to 0.89) and all-cause arrhythmia (OR 0.54, 95% CI 0.29 to 0.99) compared with controls. A significant reduction in both ITU stay (weighted mean difference (WMD) −0.44, 95% CI −0.70 to −0.17) and hospital stay (WMD −1.11, 95% CI −1.70 to −0.52) was also seen in the antioxidant group, without significant heterogeneity. Conclusions The prophylactic use of vitamins C and E may significantly reduce the incidence of POAF and all-cause arrhythmia following cardiac surgery. However, the overall quality of current studies is poor and further research should focus on adequately powered randomised controlled trials that standardise AF reporting, antioxidant protocol and the use of concomitant agents. Cost analysis should be considered to establish the potential economic benefit of antioxidant vitamin prophylaxis in POAF.

Aortic valve replacement for aortic stenosis in patients with concomitant mitral regurgitation: should the mitral valve be dealt with?

Co-existent mitral regurgitation may adversely influence both morbidity and mortality in patients undergoing aortic valve replacement for severe aortic stenosis. Whilst it is accepted that concomitant mitral intervention is required in severe, symptomatic mitral regurgitation, in cases of mild-moderate non-structural mitral regurgitation, improvement may be seen following aortic valve replacement alone, avoiding the increased risk of double-valve surgery. The exact benefit of such a conservative approach is, however, yet to be adequately quantified. We performed a systematic literature review identifying 17 studies incorporating 3053 patients undergoing aortic valve replacement for aortic stenosis with co-existing mitral regurgitation. These were meta-analysed using random effects modelling. Heterogeneity and subgroup analysis were assessed. Primary end points were change in mitral regurgitation severity and 30-day, 3-, 5- and 10-year mortality. Secondary end points were end-organ dysfunction (neurovascular, renal and respiratory), and the extent of ventricular remodelling following aortic valve replacement. Our results revealed improvement in the severity of mitral regurgitation following aortic valve replacement in 55.5% of patients, whereas 37.7% remained unchanged, and 6.8% worsened. No significant difference was seen between overall data and either the functional or moderate subgroups. The overall 30-day mortality following aortic valve replacement was 5%. This was significantly higher in moderate-severe mitral regurgitation than nil-mild mitral regurgitation both overall (p=0.002) and in the functional subgroup (p=0.004). Improved long-term survival was seen at 3, 5 and 10 years in nil-mild mitral regurgitation when compared with moderate-severe mitral regurgitation in all groups (overall p<0.0001, p<0.00001 and p=0.02, respectively). The relative risk of respiratory, renal and neurovascular complications were 7%, 6% and 4%, respectively. Reverse remodelling was demonstrated by a significant reduction in left-ventricular end-diastolic diameter and left-ventricular mass (p=0.0007 and 0.01, respectively), without significant heterogeneity. No significant change was seen in left-ventricular end-systolic diameter (p=0.10), septal thickness (p=0.17) or left atrial area (p=0.23). We conclude that despite reverse remodelling, concomitant moderate-severe mitral regurgitation adversely affects both early and late mortality following aortic valve replacement. Concomitant mitral intervention should therefore be considered in the presence of moderate mitral regurgitation, independent of the aetiology.

Bariatric Surgery Modulates Circulating and Cardiac Metabolites

Bariatric procedures such as the Roux-en-Y gastric bypass (RYGB) operation offer profound metabolic enhancement in addition to their well-recognized weight loss effects. They are associated with significant reduction in cardiovascular disease risk and mortality, which suggests a surgical modification on cardiac metabolism. Metabolic phenotyping of the cardiac tissue and plasma postsurgery may give insight into cardioprotective mechanisms. The aim of the study was to compare the metabolic profiles of plasma and heart tissue extracts from RYGB- and sham-operated Wistar rats to identify the systemic and cardiac signature of metabolic surgery. A total of 27 male Wistar rats were housed individually for a week and subsequently underwent RYGB (n = 13) or sham (n = 14) operation. At week 8 postoperation, a total of 27 plasma samples and 16 heart tissue samples (8 RYGB; 8 Sham) were collected from animals and analyzed using (1)H nuclear magnetic resonance (NMR) spectroscopy and ultra performance liquid chromatography (UPLC-MS) to characterize the global metabolite perturbation induced by RYGB operation. Plasma bile acids, phosphocholines, amino acids, energy-related metabolites, nucleosides and amine metabolites, and cardiac glycogen and amino acids were found to be altered in the RYGB operated group. Correlation networks were used to identify metabolite association. The metabolic phenotype of this bariatric surgical model inferred systematic change in both myocardial and systemic activity post surgery. The altered metabolic profile following bariatric surgery reflects an enhancement of cardiac energy metabolism through TCA cycle intermediates, cardiorenal protective activity, and biochemical caloric restriction. These surgically induced metabolic shifts identify some of the potential mechanisms that contribute toward bariatric cardioprotection through gut microbiota ecological fluxes and an enterocardiac axis to shield against metabolic syndrome of cardiac dysfunction.

Neurodegenerative disease and obesity: what is the role of weight loss and bariatric interventions?

Neurodegenerative diseases are amongst the leading causes of worldwide disability, morbidity and decreased quality of life. They are increasingly associated with the concomitant worldwide epidemic of obesity. Although the prevalence of both AD and PD continue to rise, the available treatment strategies to combat these conditions remain ineffective against an increase in global neurodegenerative risk factors. There is now epidemiological and mechanistic evidence associating obesity and its related disorders of impaired glucose homeostasis, type 2 diabetes mellitus and metabolic syndrome with both AD and PD. Here we describe the clinical and molecular relationship between obesity and neurodegenerative disease. Secondly we outline the protective role of weight loss, metabolic and caloric modifying interventions in the context of AD and PD. We conclude that the application of caloric restriction through dietary changes, bariatric (metabolic) surgery and gut hormone therapy may offer novel therapeutic strategies against neurodegenerative disorders. Investigating the protective mechanisms of weight loss, metabolic and caloric modifying interventions can increase our understanding of these major public health diseases and their management.

Meta-analysis of robot-assisted vs conventional laparoscopic and open pyeloplasty in children

To critically analyse outcomes for robot‐assisted pyeloplasty (RAP) vs conventional laparoscopic pyeloplasty (LP) or open pyeloplasty (OP) by systematic review and meta‐analysis of published data.

Antioxidant vitamins in the prevention of atrial fibrillation: what is the evidence?

Atrial fibrillation (AF) is the most common sustained arrhythmia that is associated with significant morbidity and mortality. Current available therapies remain inadequate in symptom control and secondary prevention and are often associated with significant side effects. The mechanisms underlying the pathogenesis of AF are poorly understood, although electrophysiological remodeling has been described as an important initiating step. Recently, increasing evidence implicates oxidative stress and inflammation in the pathogenesis of AF. We searched the literature for evidence to support the use of antioxidant vitamins C and E in the prevention of AF. These vitamins, through their reactive-oxygen-species- (ROS-) scavenging effect, have shown a role in AF prevention in both animal and small clinical studies. The available evidence, however, is currently insufficient to support recommendations for their use in the wider patient population. Larger-scale clinical studies are required to confirm these preliminary results. Research is also required to further the understanding of the processes involved in the pathogenesis of AF and the role of antioxidant therapies to prevent the arrhythmia.

Online social networking services in the management of patients with diabetes mellitus: Systematic review and meta-analysis of randomised controlled trials

AIMS Social networking services (SNS) can facilitate real-time communication and feedback of blood glucose and other physiological data between patients and healthcare professionals. This systematic review and meta-analysis aims to summarise the current evidence surrounding the role of online social networking services in diabetes care. METHODS We performed a systematic literature review of the Medline, EMBASE and PsychINFO databases of all studies reporting HbA1c (glycated haemoglobin) as a measure of glycaemic control for social networking services in diabetes care. HbA1c, clinical outcomes and the type of technology used were extracted. Study quality and publication bias were assessed. RESULTS SNS interventions beneficially reduced HbA1c when compared to controls, which was confirmed by sensitivity analysis. SNS interventions also significantly improved systolic and diastolic blood pressure, triglycerides and total cholesterol. Subgroup analysis according to diabetes type demonstrated that Type 2 diabetes patients had a significantly greater reduction in HbA1c than those with Type 1 diabetes. CONCLUSIONS Online SNS provide a novel, feasible approach to improving glycaemic control, particularly in patients with Type 2 diabetes. Further mechanistic and cost-effectiveness studies are required to improve our understanding of SNS and its efficacy in diabetes care.

Do miniaturized extracorporeal circuits confer significant clinical benefit without compromising safety? A meta-analysis of randomized controlled trials.

Miniaturized extracorporeal circulation (mECC) attempts to reduce the adverse effects of conventional extracorporeal circulation (CECC) bypass. However, the potential benefits remain unclear and safety concerns persist. A systematic literature review identified 29 studies incorporating 2,355 patients: 1,181 (50.1%) who underwent cardiac surgery with CECC and 1,174 (49.9%) with mECC. These were meta-analyzed using random effects modeling. Heterogeneity, subgroup analysis, and risk of bias were assessed. Primary endpoints were 30-day mortality, neurovascular compromise, and end organ dysfunction. Secondary endpoints were length of stay and transfusion burden. Miniaturized extracorporeal circulation significantly reduced postoperative arrhythmias (p = 0.03), but no significant difference in 30-day mortality, neurocognitive disturbance, cerebrovascular events, renal failure, or myocardial infarction was identified. Miniaturized extracorporeal circulation also significantly reduced mean blood loss (p < 0.00001) and number of patients transfused (p < 0.00001); however, duration of hospitalization, units transfused per patient, chest tube drainage, and revision for rebleeding remained unchanged. Subgroup analysis of larger studies (10 studies, n ≥ 31) showed mECC to significantly reduce ventilation period, hospital stay, and intensive care unit (ICU) stay. Similarly, a significant reduction in neurocognitive disturbance was seen in studies with closely matched demographic groups. Miniaturized extracorporeal circulation is not associated with increased cerebrovascular injury and may confer an advantage, reducing postoperative arrhythmia, blood loss, and transfusion burden.

Obesity-related cardiorenal disease: the benefits of bariatric surgery

The inexorable increase in the prevalence of obesity is a global health concern, which will result in a concomitant escalation in health-care costs. Obesity-related metabolic syndrome affects approximately 25% of adults and is associated with cardiovascular and renal disease. The heart and kidneys are physiologically interdependent, and the pathological effects of obesity can lead to cardiorenal syndrome and, ultimately, kidney and heart failure. Weight loss can prevent or ameliorate obesity-related cardiorenal syndrome, but long-term maintenance of a healthy weight has been difficult to achieve through lifestyle changes or pharmacotherapy. Bariatric surgery offers both sustained weight loss and favourable metabolic changes, including dramatic improvements in glycaemic control and symptoms of type 2 diabetes mellitus. Procedures such as Roux-en-Y gastric bypass offer immediate multisystemic benefits, including bile flow alteration, reduced gastric size, anatomical gut rearrangement and altered flow of nutrients, vagal manipulation and enteric hormone modulation. In patients with cardiorenal syndrome, bariatric surgery also offers renoprotection and cardioprotection, and attenuates both kidney and heart failure by improving organ perfusion and reversing metabolic dysfunction. However, further research is required to understand how bariatric surgery acts on the cardiorenal axis, and its pioneering role in novel treatments and interventions for cardiorenal disease.