Chronic thoracic pain after cardiac surgery: role of inflammation and biomechanical sternal stability.

Introduction: The pathogenesis of chronic chest pain after cardiac surgery has not been determinate. If left untreated, postoperative sternal pain reduces the quality of life and patient satisfaction with cardiac surgery. The purpose of the study was to examine the effect of chest inflammation on postoperative pain, risk factors for chronic pain after cardiac surgery and to explore how chest reconstruction was associated with the intensity of pain. Methods: The authors performed a study of acute and chronic thoracic pain after cardiac surgery in patients with and without sternal infection and compared different techniques for chest reconstruction. 42 high-risk patients for the development of mediastinitis were included. Patients with mediastinitis received chest reconstruction (group 1). Their demographics and risk factors were matched with no-infection patients with chest reconstruction (group 2) and subjects who underwent conventional sternal closure (group 3). Chronic pain was assessed by the numeric rating scale after surgery. Results: The assessment of the incidence and intensity of chest pain at 3 months post-surgery demonstrated that 14 out of 42 patients across all groups still experienced chronic pain. Specifically, in group 1 with sternal infection five patients had mild pain, while one patient experienced mild pain in group 2, and eight patients in group 3. Also, follow-up results indicated that the highest pain score was in group 3. While baseline levels of cytokines were increased among patients with sternal infection, at discharge only the level of interleukin 6 remained high compared to no infection groups. Compared to conventional closure, after chest reconstruction, we found better healing scores at 3-month follow-up and a higher percentage of patients with the complete sternal union. Conclusions: Overall, 14 out of 42 patients have chronic pain after cardiac surgery. The intensity of the pain in mediastinitis patients significantly decreased at 3 months follow-up after chest reconstruction. Thus, post-surgery mediastinitis is not a determining factor for development the chronic chest pain. There is no correlation between cytokines levels and pain score except interleukin 6 which remains elevated for a long time after treatment. Correlation between sternal healing score and chronic chest pain was demonstrated.

Multivariable regression: understanding one of medicine's most fundamental statistical tools.

Multivariable regression is a fundamental tool that drives observational research in orthopaedic surgery. However, regression analyses are not always implemented correctly. This study presents a basic overview of regression analyses and reviews frequent points of confusion. Topics include linear, logistic, and time-to-event regressions, causal inference, confounders, overfitting, missing data, multicollinearity, interactions, and key differences between multivariable versus multivariate regression. The goal is to provide clarity regarding the use and interpretation of multivariable analyses for those attempting to increase their statistical literacy in orthopaedic research.

Unsupervised machine learning methods and emerging applications in healthcare.

Unsupervised machine learning methods are important analytical tools that can facilitate the analysis and interpretation of high-dimensional data. Unsupervised machine learning methods identify latent patterns and hidden structures in high-dimensional data and can help simplify complex datasets. This article provides an overview of key unsupervised machine learning techniques including K-means clustering, hierarchical clustering, principal component analysis, and factor analysis. With a deeper understanding of these analytical tools, unsupervised machine learning methods can be incorporated into health sciences research to identify novel risk factors, improve prevention strategies, and facilitate delivery of personalized therapies and targeted patient care.Level of evidence: I.

Choosing the appropriate measure of central tendency: mean, median, or mode?

Mean, median, and mode are among the most basic and consistently used measures of central tendency in statistical analysis and are crucial for simplifying data sets to a single value. However, there is a lack of understanding of when to use each metric and how various factors can impact these values. The aim of this article is to clarify some of the confusion related to each measure and explain how to select the appropriate metric for a given data set. The authors present this work as an educational resource, ensuring that these common statistical concepts are better understood throughout the Orthopedic research community.

Fragility Part I: a guide to understanding statistical power.

The aim of this paper is to close the knowledge-to-practice gap around statistical power. We demonstrate how four factors affect power: p value, effect size, sample size, and variance. This article further delves into the advantages and disadvantages of a priori versus post hoc power analyses, though we believe only understanding of the former is essential to addressing the present-day issue of reproducibility in research. Upon reading this paper, physician-scientists should have expanded their arsenal of statistical tools and have the necessary context to understand statistical fragility.

Picking apart p values: common problems and points of confusion.

Due to its frequent misuse, the p value has become a point of contention in the research community. In this editorial, we seek to clarify some of the common misconceptions about p values and the hazardous implications associated with misunderstanding this commonly used statistical concept. This article will discuss issues related to p value interpretation in addition to problems such as p-hacking and statistical fragility; we will also offer some thoughts on addressing these issues. The aim of this editorial is to provide clarity around the concept of statistical significance for those attempting to increase their statistical literacy in Orthopedic research.

Efficient cardiac gene transfer and early-onset expression of a synthetic adeno-associated viral vector, Anc80L65, after intramyocardial administration.

OBJECTIVE: Gene therapy is a promising approach in the treatment of cardiovascular diseases. Preclinical and clinical studies have demonstrated that adeno-associated viral vectors are the most attractive vehicles for gene transfer. However, preexisting immunity, delayed gene expression, and postinfection immune response limit the success of this technology. The aim of this study was to investigate the efficacy of the first synthetic adeno-associated viral lineage clone, Anc80L65, for cardiac gene therapy. METHODS: By combining 2 different reporter approaches by fluorescence with green fluorescent protein and bioluminescence (Firefly luciferase), we compared transduction efficiency of Anc80L65 and adeno-associated virus, serotype 9 in neonatal rat cardiomyocytes ex vivo and rat hearts in vivo after intramyocardial and intracoronary administration. RESULTS: In cardiomyocytes, Anc80L65 provided a green fluorescent protein expression of 28.9% (36.4 ± 3.34 cells/field) at 24 hours and approximately 100% on day 7. In contrast, adeno-associated virus, serotype 9 green fluorescent protein provided minimal green fluorescent protein expression of 5.64% at 24 hours and 11.8% on day 7. After intramyocardial injection, vector expression peaked on day 7 with Anc80L65; however, with adeno-associated virus, serotype 9 the peak expression was during week 6. Administration of Anc80L65 demonstrated significantly more efficient expression of reporter gene than after adeno-associated virus, serotype 9 at 6 weeks (6.81 ± 0.64 log10 gc/100 ng DNA vs 6.49 ± 0.28 log10 gc/100 ng DNA, P < .05). These results were consistent with the amount of genome copy per cell observed in the heart. CONCLUSIONS: Anc80L65 vector allows fast and robust gene transduction compared with adeno-associated virus, serotype 9 vector in cardiac gene therapy. Anc80L65 did not adversely affect cardiac function and caused no inflammatory response or toxicity.

Inflammatory Responses with Left Ventricular Compromise after Induction of Myocardial Infarcts in Sheep (Ovis aries).

Ischemic myocardial disease is a major cause of death among humans worldwide; it results in scarring and pallor of the myocardium and triggers an inflammatory response that contributes to impaired left ventricular function. This response includes and is evidenced by the production of several inflammatory cytokines including TNFα, IL1ß, IL4, IFNγ, IL10 and IL6. In the current study, myocardial infarcts were induced in 6 mo old male castrated sheep by ligation of the left circumflex obtuse marginal arteries (OM 1 and 2). MRI was used to measure parameters of left ventricular function that include EDV, ESV, EF, SVI, dp/dt max and dp/dt min at baseline and at 4 wk and 3 mo after infarct induction. We also measured serum concentrations of an array of cytokines. Postmortem histologic findings corroborate the existence of left ventricular myocardial injury and deterioration. Our data show a correlation between serum cytokine concentrations and the development of myocardial damage and left ventricular functional compromise.

Use of longitudinal rigid sternal fixation in prevention and treatment of wound complications among high-risk patients after cardiac surgery.

BACKGROUND: Traditionally, wire cerclage closure has been used to reapproximate the sternum after cardiac surgery. Recent evidence suggests that rigid sternal fixation may reduce the risk of wound complications. The aim of this study was to analyze our 10-year experience with longitudinal rigid sternal fixation (LRSF) for prevention and treatment of wound complications in high-risk patients. METHODS: We reviewed data from cardiac surgical database of patients who underwent LRSF, and compared their outcomes with conventional wire cerclage closure (CWS). Among these 319 patients were designated as having high-risk for the development of deep wound complications and received primary LRSF (treatment group). We matched their outcomes with 319 patients who met indications for LRSF however, underwent standard closure with CWC (control group). RESULTS: Both groups were comparable regarding preoperative and intraoperative variables. The benefit observed among matched patients who had undergone LRSF was largely driven by a decreased rate of deep wound infections (0.63% vs. 3.45% vs., p < .01), 30-day mortality (1.57% vs. 5.96%) and hospital length (8.2 vs. 11.7 days) p < .05, respectively. A multivariate logistic regression analysis found four independent risk factors for the development of sternal dehiscence. Sternal healing evaluated by computerized tomography scan using 6-point scale at 3 months after surgery was superior in LRSF patients. Pain scores were significantly lower in LRSF patients as well. CONCLUSIONS: In patients with an increased risk for sternal instability and wound infections after cardiac surgery, sternal reconstruction using LRSF is an effective technique to stabilize sternum for preventive and treatment purposes.