Do age-associated changes of voltage-gated sodium channel isoforms expressed in the mammalian heart predispose the elderly to atrial fibrillation?

© The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. The prevalence of the disease increases with age, strongly implying an age-related process underlying the pathology. At a time when people are living longer than ever before, an exponential increase in disease prevalence is predicted worldwide. Hence unraveling the underlying mechanics of the disease is paramount for the development of innovative treatment and prevention strategies. The role of voltage-gated sodium channels is fundamental in cardiac electrophysiology and may provide novel insights into the arrhythmogenesis of AF. Nav1.5 is the predominant cardiac isoform, responsible for the action potential upstroke. Recent studies have demonstrated that Nav1.8 (an isoform predominantly expressed within the peripheral nervous system) is responsible for cellular arrhythmogenesis through the enhancement of pro-arrhythmogenic currents. Animal studies have shown a decline in Nav1.5 leading to a diminished action potential upstroke during phase 0. Furthermore, the study of human tissue demonstrates an inverse expression of sodium channel isoforms; reduction of Nav1.5 and increase of Nav1.8 in both heart failure and ventricular hypertrophy. This strongly suggests that the expression of voltage-gated sodium channels play a crucial role in the development of arrhythmias in the diseased heart. Targeting aberrant sodium currents has led to novel therapeutic approaches in tackling AF and continues to be an area of emerging research. This review will explore how voltage-gated sodium channels may predispose the elderly heart to AF through the examination of laboratory and clinical based evidence

Do T2DM and Hyperglycaemia Affect the Expression Levels of the Regulating Enzymes of Cellular O-GlcNAcylation in Human Saphenous Vein Smooth Muscle Cells?

Protein O-GlcNAcylation, a dynamic and reversible glucose-dependent post-translational modification of serine and threonine residues on target proteins, has been proposed to promote vascular smooth muscle cell proliferation and migration events implicated in vein graft failure (VGF). Therefore, targeting the enzymes (glutamine fructose-6P amidotransferase (GFAT), O-GlcNAc transferase (OGT), and O-GlcNAcase (OGA)) that regulate cellular O-GlcNAcylation could offer therapeutic options to reduce neointimal hyperplasia and venous stenosis responsible for VGF. However, it is unclear how type 2 diabetes mellitus (T2DM) and hyperglycaemia affect the expression of these enzymes in human saphenous vein smooth muscle cells (HSVSMCs), a key cell type involved in the vascular dysfunction responsible for saphenous VGF. Therefore, our aim was to assess whether T2DM and hyperglycaemia affect GFAT, OGT, and OGA expression levels in HSVSMCs in vitro. Expression levels of GFAT, OGT, and OGA were determined in low-passage HSVSMCs from T2DM and non-T2DM patients, and in HSVSMCs treated for 48 h with hyperglycaemic (10 mM and 25 mM) glucose concentrations, by quantitative immunoblotting. Expression levels of OGT, OGA, and GFAT were not significantly different in HSVSMC lysates from T2DM patients versus non-T2DM controls. In addition, treatment with high glucose concentrations (10 mM and 25 mM) had no significant effect on the protein levels of these enzymes in HSVSMC lysates. From our findings, T2DM and hyperglycaemia do not significantly impact the expression levels of the O-GlcNAcylation-regulating enzymes OGT, OGA, and GFAT in HSVSMCs. This study provides a foundation for future studies to assess the role of O-GlcNAcylation on VGF in T2DM

Colorectal Cancer Presenting as Single Pulmonary Hilar Lymph Node Metastasis

Colorectal carcinoma is the second biggest cancer responsible for mortality. Lung metastasis is the commonest, following the liver. It is not uncommon to perform pulmonary metastasectomy and identify mediastinal metastasis. Previous studies have identified incidental lymph node involvement following routine mediastinal lymph node clearance in 20–50% of cases. However, solitary intrathoracic lymph node metastasis is exceedingly rare. Even when present, it is usually metachronous. In our case, we present an exceedingly rare case whereby the intrathoracic lymph node metastasis is solitary, not accompanying pulmonary disease and with no liver metastasis. We also review the evidence for mediastinal lymphadenectomy in the literature

Microplastics in the surgical environment

Atmospheric microplastics (MPs) have been consistently detected within indoor and outdoor air samples. Locations with high human activity are reported to have high MP levels. The aim was to quantify and characterise the MPs present within the surgical environment over a one-week sampling period. MPs were collected in samplers placed around an operating theatre and adjoining anaesthetic room at 12 hour intervals. Particles were filtered onto 0.02 micron membranes and analysed using micro-Fourier-transform infrared spectroscopy. The number of MPs identified during the working day sampling period varied, with a mean of 1,924 ± 3,105 MP m-2 day-1 and a range of 0 – 9,258 MP m-2 day-1 observed in the theatre, compared with a mean of 541 ± 969 MP m-2 day-1 and a range of 0 – 3,368 MP m-2 day-1 for the anaesthetic room. Across both rooms and at all sampling points, an increase in levels with a decrease in MP size was observed. Identified particles consisted of mainly fragment shaped MPs (78%) with polyethylene terephthalate (37%), polypropylene (25%), polyethylene (7%) and nylon (13%) representing the most abundant polymer types. MPs were not detected in the theatre during non-working hours. The results provide novel information on defining polymer levels and types, in a room environment where the use of single plastics has been regarded as beneficial to practice. These results can inform cellular toxicity studies, investigating the consequences of human MP exposure as well as represent a potentially novel route of exposure for humans for this emerging contaminant of concern, via surgery

Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure

Current trends in cannulation and neuroprotection during surgery of the aortic arch in Europe†‡

OBJECTIVES To conduct a survey across European cardiac centres to evaluate the methods used for cerebral protection during aortic surgery involving the aortic arch. METHODS All European centres were contacted and surgeons were requested to fill out a short, comprehensive questionnaire on an internet-based platform. One-third of more than 400 contacted centres completed the survey correctly. RESULTS The most preferred site for arterial cannulation is the subclavian-axillary, both in acute and chronic presentation. The femoral artery is still frequently used in the acute condition, while the ascending aorta is a frequent second choice in the case of chronic presentation. Bilateral antegrade brain perfusion is chosen by the majority of centres (2/3 of cases), while retrograde perfusion or circulatory arrest is very seldom used and almost exclusively in acute clinical presentation. The same pumping system of the cardio pulmonary bypass is most of the time used for selective cerebral perfusion, and the perfusate temperature is usually maintained between 22 and 26°C. One-third of the centres use lower temperatures. Perfusate flow and pressure are fairly consistent among centres in the range of 10-15 ml/kg and 60 mmHg, respectively. In 60% of cases, barbiturates are added for cerebral protection, while visceral perfusion still receives little attention. Regarding cerebral monitoring, there is a general tendency to use near-infrared spectroscopy associated with bilateral radial pressure measurement. CONCLUSIONS These data represent a snapshot of the strategies used for cerebral protection during major aortic surgery in current practice, and may serve as a reference for standardization and refinement of different approache

Quality of Life after Type A Aortic Dissection Surgery in the United Kingdom: The QUADS Study

\ua9 2025. The Author(s).Background Acute Type A aortic dissection (TAAD) is a life-threatening condition that carries significant mortality and morbidity; a proportion of the survivors might require further aortic procedures in the mid-/long-term follow-up. Quality of life (QoL) after TAAD is not well studied. Quality of life after Type A Aortic Dissection Surgery (QUADS) is the first multicentre study to assess QoL in survivors of surgically treated TAAD. Methods A tailored questionnaire for survivors of TAAD was designed with patient and public involvement. Patients who underwent surgery from 2018 to 2022 in eight United Kingdom centres were invited to participate. Preoperative, intraoperative, and postoperative prospectively collected data were collated and analyzed retrospectively. The data were analyzed with SPSS v29. Patient\u27s questionnaire was validated with a Cronbach\u27s alpha analysis, exploratory factor analysis, and AMOS confirmatory factor analysis. Three groups were created according to QoL (Good, Fair, Poor). Results A total of 162 patients were recruited. Majority were male with a mean age of 63 years (24-92). Surgical procedures for TAAD were root and ascending aorta replacement (n = 61, 38%), ascending (n = 81, 50%), and/or arch replacement (n = 20, 12%). Eleven patients (7%) required later intervention. Patient\u27s answers regarding overall QoL were good (n = 67, 41%), fair (n = 89, 55%), and poor (n = 6, 4%). Neurological complications, circulatory arrest duration, reoperation for bleeding, postoperative myocardial infraction, arrhythmias, wound infection, and patient destination at discharge have been identified as main variables impacting on QoL after TAAD surgery across different domains of this questionnaire. Conclusion QUADS questionnaire is the first tailored and validated questionnaire for TAAD survivors. Results in the United Kingdom population suggest that it is a useful tool to assess QoL after TAAD surgery

PRESS survey: PREvention of surgical site infection—a global pan-specialty survey of practice protocol

BackgroundSurgical site infections (SSI) complicate up to 40% of surgical procedures, leading to increased patient morbidity and mortality. Previous research identified disparities in SSI prevention guidelines and clinical practices across different institutions. The study aims to identify variations in SSI prevention practices within and between specialties and financial systems and provide a representation of existing SSI preventative measures to help improve the standardization of SSI prevention practices.MethodsThis collaborative cross-sectional survey will be aimed at pan-surgical specialties internationally. The study has been designed and will be reported in line with the CROSS and CHERRIES standards. An international study steering committee will design and internally validate the survey in multiple consensus-based rounds. This will be based on SSI prevention measures outlined in the CDC (2017), WHO (2018), NICE (2019), Wounds UK (2020) and the International Surgical Wound Complications Advisory Panel (ISWCAP) guidelines. The questionnaire will include demographics, SSI surveillance, preoperative, peri-operative and postoperative SSI prevention. Data will be collected on participants' surgical specialty, operative grade, of practice and financial healthcare system of practice. The online survey will be designed and disseminated using Qualtrics XM Platform™ through national and international surgical colleges and societies, in addition to social media and snowballing. Data collection will be open for 3 months with reminders, and raking will be used to ascertain the sample. Responses will be analyzed, and the chi-square test used to evaluate the impact of SSI prevention variables on responses.DiscussionCurrent SSI prevention practice in UK Vascular surgery varies considerably, with little consensus on many measures. Given the inconsistency in guidelines on how to prevent SSIs, there is a need for standardization. This survey will investigate the disparity in SSI preventative measures between different surgical fields and countries

Intersectionality of inequalities in revascularization and outcomes for acute coronary syndrome in England: nationwide linked cohort study

\ua9 The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. Background: Inequalities in access to care for women, people of non-white ethnicity, who live in areas of social deprivation, and with multiple long-term conditions lead to inequity of outcomes. We investigated the intersectionality of these causes of health inequality on coronary revascularization and clinical outcomes for admissions with acute coronary syndrome (ACS). Methods and results: We included hospital admissions in England for types of ACS from April 2015 to April 2018 and linked Hospital Episode Statistics to the Office for National Statistics mortality data. The primary outcome was time to all-cause mortality. Time-to-event analyses examined the associations of sex, ethnicity, and socioeconomic deprivation with revascularization. Of 428 700 admissions with ACS, 212 015 (48.8%) received revascularization within 30 days. Women, black ethnicity, multimorbid, and frail patients were less likely to undergo revascularization. South Asian ethnicities had higher [hazard ratio (HR) = 1.15, 95% confidence interval (CI) 1.14–1.17] revascularization rates and comparable risk-adjusted survival but higher re-admission rates when compared to other ethnic groups. Women had higher 1-year all-cause [25.5% vs. 14.7%—ST-elevation myocardial infarction (STEMI); 24.9% vs. 18.7%—non-ST-elevation myocardial infarction (NSTEMI)] and cardiovascular (22.6% vs. 13.2%—STEMI; 20.3% vs. 15.6%—NSTEMI) mortality than men. After adjusting for confounders, women had a lower all-cause mortality when compared to men. Discussion: Outcomes attributed to women and people of South Asian ethnicity may be attributable to age, comorbidity and frailty at presentation. Black ethnicity, geography, and social deprivation may be sources of inequality. These findings highlight the unmet need and may provide potential targets for interventions that address inequalities

Microplastics in cardiopulmonary bypass: quantification and characterisation of particles across systems

OBJECTIVESThis study determines the microplastic (MP) levels, dimension, shape, and chemical composition generated from conventional cardiopulmonary bypass and minimally invasive extracorporeal circulation (MiECC) circuits.METHODSIn vitro conventional and MiECC circuits, mimicking realistic setups with 2 L of Hartmann’s solution were run for 90 min (n = 3 circuit runs each), filtered, and analysed using micro-Fourier transform infrared spectroscopy alongside procedural blanks (n = 5).RESULTSConventional circuits produced 60.4 ± 7.6 MPs L−1h−1 (77.0% of the total particles). MiECC circuits produced 48.4 ± 31.3 MPs L−1h−1 (45.3% of total particles). MP levels in each circuit type were significantly elevated compared with procedural blank (n = 5) samples (5.6 ± 10.4 MPs L−1h−1) but did not differ with respect to the other. Twenty different MP polymer types were detected whereby polydimethyl siloxane, poly(decyl methacrylate), and poly(N-butyl methacrylate) represented the most MPs within conventional circuits. For MiECC, the most abundant were polypropylene, polyethylene, and polyamide. Average MP lengths differed significantly: 93.5 ± 98.6 µm (conventional) versus 62.0 ± 54.4 µm (MiECC) (P < 0.001), although widths did not differ. Film particles (48.2%) were the predominant shape for conventional circuits and fragments (50.5%) for MiECC.CONCLUSIONSSignificant levels of MP particles were produced across the two systems. Future studies can determine the time points at which they are produced in machine use, to mitigate their production, as well as inform cell/tissue culture investigations into the clinical significance of their introduction into patients undergoing cardiac surgery