Meta-analysis: A practical decision making tool for surgeons

AbstractBackgroundThe exponential rise in published medical research on a yearly basis demands a method to summarise best evidence towards its application to patient care in clinical practice. A robust meta-analysis is a valid tool. It is often considered to be a simple process of pooling results from different studies. This is not true. It appears that surgeons lack a reference guide to help them conduct and appraise a meta-analysis.MethodsThis paper provides a structural framework to perform a meta-analysis. It guides the surgeon on a journey from identification of the correct clinical question to data analysis and through to producing a structured report. Statistical methods are discussed briefly as most commercial software calculates most results in the background. An example of a recent meta-analysis is given. However, important caveats are mentioned as there are limitations of the meta-analytical technique.ConclusionWhereas meta-analyses of homogeneous studies are the highest form of evidence, poorly conducted meta-analyses create confusion and serve to harm the patient. Surgeons practising their art in an era of evidence-based surgery need to understand the principles of meta-analyses

Allelic and phenotypic heterogeneity in Junctophillin-3 related neurodevelopmental and movement disorders.

Junctophilin-3 belongs to a triprotein junctional complex implicated in the regulation of neuronal excitability and involved in the formation of junctional membrane structures between voltage-gated ion channels and endoplasmic (ryanodine) reticular receptors. A monoallelic trinucleotide repeat expansion located within the junctophilin-3 gene (JPH3) has been implicated in a rare autosomal dominant (AD) late-onset (and progressive) disorder clinically resembling Huntington disease (HD), and known as HD-like 2 (HDL2; MIM# 606438). Although the exact molecular mechanisms underlying HDL2 has not yet been fully elucidated, toxic gain-of-function of the aberrant transcript (containing the trinucleotide repeat) and loss of expression of (full-length) junctophilin-3 have both been implicated in HDL2 pathophysiology. In this study, we identified by whole exome sequencing (WES) a JPH3 homozygous truncating variant [NM_020655.4: c.17405dup; p.(Val581Argfs*137)]. in a female individual affected with genetically undetermined neurodevelopmental anomalies (including delayed motor milestones, abnormal social communication, language difficulties and borderline cognitive impairment) and paroxysmal attacks of dystonia since her early infancy. Our study expands the JPH3-associated mutational spectrum and clinical phenotypes, implicating the loss of Junctophilin-3 in heterogeneous neurodevelopmental phenotypes and early-onset paroxysmal movement disorders

Laparoscopic Approach to Incarcerated and Strangulated Inguinal Hernias

Introduction: Acute inguinal hernias are a common presentation as surgical emergencies, which have been routinely managed with open surgery. In recent years, the laparoscopic approach has been described by several authors but has been controversial amongst surgeons. We describe the laparoscopic approach to incarcerated/strangulated inguinal hernias based on a review of the literature with regards to its feasibility in laparoscopically managing the acute hernia presentation. Methods: A systematic literature search was carried out including Medline with PubMed as the search engine, and Ovid, Embase, Cochrane Collaboration, and Google Scholar databases to identify articles reporting on laparoscopic treatment, reduction, and repair of incarcerated or strangulated inguinal hernias from 1989 to 2008. Results: Forty-three articles were found, and 7 were included according to the inclusion criteria set. Articles reporting on the use of laparoscopy for the evaluation of the hernia but not reducing and repairing it, the use of the open technique, elective hernia repairs, pediatric series, review articles, and other kinds of hernias were excluded after title and abstract review. This resulted in 16 articles that were reviewed in full. Of these 16 articles, 7 reported on the use of the laparoscopic approach exclusively. From these 7 studies, there were 328 cases reported, 6 conversions, average operating time of 61.3 minutes (SD 12.3), average hospital stay of 3.8 days (SD 1.2), 34 complications (25 of which were reported as minor), and 17 bowel resections performed either laparoscopically or through a minilaparotomy incision guided laparoscopically. Conclusion: The laparoscopic repair is a feasible procedure with acceptable results; however, its efficacy need

The role of minimal access valve surgery in the elderly. A meta-analysis of observational studies

Background Minimal access valve surgery, both mitral and aortic, may be related to improvement in specific post-operative outcomes, therefore may be beneficial for the subgroup of the elderly referred for valve surgery. Methods A systematic literature review identified several different studies, of which 6 fulfilled criteria for meta-analysis. Outcomes for a total of 1347 patients (675 conventional standard sternotomy and 672 minimally invasive valve surgery) were assessed with a meta-analysis using random effects modeling. Heterogeneity, subgroup analysis with quality scoring were also assessed. The primary endpoint was early mortality. Secondary endpoints included intra and post-operative outcomes. Results In the context of elderly patients, minimal access valve surgery conferred comparable early mortality to standard sternotomy (odd ratio (OR) 0.79, CI [0.40,1.56], p\ua0=\ua00.50) with no heterogeneity (p\ua0=\ua00.13); it was also associated with reduced mechanical intubation time (OR 0.48, CI [0.30,0.78], p\ua0=\ua00.003) and reduced post-operative length of stay (weighted mean difference (WMD)\ua0 122.91, CI [ 123.09,\ua0 122.74] p\ua0<\ua00.00001), however both cardio-pulmonary bypass time and cross clamp time were longer (WMD 24.29, CI [22.97, 25.61] p\ua0<\ua00.00001 and WMD 8.61, CI [7.61, 9.61], p\ua0<\ua00.00001, respectively); subgroup analysis demonstrated statistically significant reduced post-operative length of stay for both minimally invasive aortic and mitral surgery (WMD\ua0 122.84, CI [ 123.07,\ua0 122.60] p\ua0<\ua00.00001 and WMD\ua0 122.98, CI [ 123.25,\ua0 122.71] p\ua0<\ua00.00001 respectively). Conclusions Despite a prolonged cardiopulmonary bypass and cross clamp time, minimally invasive valve surgery is a safe alternative to standard sternotomy in the elderly, with similar early mortality, and improvements in intubation time as well as length of stay

Evaluation of computational methodologies for accurate prediction of wall shear stress and turbulence parameters in a patient-specific aorta

Background: Recent studies suggest that blood flow in main arteries is intrinsically disturbed, even under healthy conditions. Despite this, many computational fluid dynamics (CFD) analyses of aortic haemodynamics make the assumption of laminar flow, and best practices surrounding appropriate modelling choices are lacking. This study aims to address this gap by evaluating different modelling and post-processing approaches in simulations of a patient-specific aorta. Methods: Magnetic resonance imaging (MRI) and 4D flow MRI from a patient with aortic valve stenosis were used to reconstruct the aortic geometry and derive patient-specific inlet and outlet boundary conditions. Three different computational approaches were considered based on assumed laminar or assumed disturbed flow states including low-resolution laminar (LR-laminar), high-resolution laminar (HR-Laminar) and large-eddy simulation (LES). Each simulation was ran for 30 cardiac cycles and post-processing was conducted on either the final cardiac cycle, or using a phase-averaged approach which utilised all 30 simulated cycles. Model capabilities were evaluated in terms of mean and turbulence-based parameters. Results: All simulation types, regardless of post-processing approach could correctly predict velocity values and flow patterns throughout the aorta. Lower resolution simulations could not accurately predict gradient-derived parameters including wall shear stress and viscous energy loss (largest differences up to 44.6% and 130.3%, respectively), although phase-averaging these parameters improved predictions. The HR-Laminar simulation produced more comparable results to LES with largest differences in wall shear stress and viscous energy loss parameters up to 5.1% and 11.6%, respectively. Laminar-based parameters were better estimated than turbulence-based parameters. Conclusions: Our findings suggest that well-resolved laminar simulations can accurately predict many laminar-based parameters in disturbed flows, but there is no clear benefit to running a HR-Laminar simulation over an LES simulation based on their comparable computational cost. Additionally, post-processing ‘typical’ laminar simulation results with a phase-averaged approach is a simple and cost-effective way to improve accuracy of lower-resolution simulation results

Analysis of turbulence effects in a patient-specific aorta with aortic valve stenosis

Blood flow in the aorta is often assumed laminar, however aortic valve pathologies may induce transition to turbulence and our understanding of turbulence effects is incomplete. The aim of the study was to provide a detailed analysis of turbulence effects in aortic valve stenosis (AVS). Methods: Large-eddy simulation (LES) of flow through a patient-specific aorta with AVS was conducted. Magnetic resonance imaging (MRI) was performed and used for geometric reconstruction and patient-specific boundary conditions. Computed velocity field was compared with 4D flow MRI to check qualitative and quantitative consistency. The effect of turbulence was evaluated in terms of fluctuating kinetic energy, turbulence-related wall shear stress (WSS) and energy loss. Results: Our analysis suggested that turbulence was induced by a combination of a high velocity jet impinging on the arterial wall and a dilated ascending aorta which provided sufficient space for turbulence to develop. Turbulent WSS contributed to 40% of the total WSS in the ascending aorta and 38% in the entire aorta. Viscous and turbulent irreversible energy losses accounted for 3.9 and 2.7% of the total stroke work, respectively. Conclusions: This study demonstrates the importance of turbulence in assessing aortic haemodynamics in a patient with AVS. Neglecting the turbulent contribution to WSS could potentially result in a significant underestimation of the total WSS. Further work is warranted to extend the analysis to more AVS cases and patients with other aortic valve diseases

Using Higher Moments of Fluctuations and their Ratios in the Search for the QCD Critical Point

The QCD critical point can be found in heavy ion collision experiments via the non-monotonic behavior of many fluctuation observables as a function of the collision energy. The event-by-event fluctuations of various particle multiplicities are enhanced in those collisions that freeze out near the critical point. Higher, non-Gaussian, moments of the event-by-event distributions of such observables are particularly sensitive to critical fluctuations, since their magnitude depends on the critical correlation length to a high power. We present quantitative estimates of the contribution of critical fluctuations to the third and fourth moments of the pion, proton and net proton multiplicities, as well as estimates of various measures of pion-proton correlations, all as a function of the same five non-universal parameters, one of which is the correlation length that parametrizes proximity to the critical point. We show how to use nontrivial but parameter independent ratios among these more than a dozen fluctuation observables to discover the critical point. We also construct ratios that, if the critical point is found, can be used to overconstrain the values of the non-universal parameters.Comment: 16 pages, 5 figures. Version to appear in PRD. Footnote and reference adde