Basement membrane proteins in various arterial beds from individuals with and without type 2 diabetes mellitus: a proteome study.

BACKGROUND: Basement membrane (BM) accumulation is a hallmark of micro-vessel disease in diabetes mellitus (DM). We previously reported marked upregulation of BM components in internal thoracic arteries (ITAs) from type 2 DM (T2DM) patients by mass spectrometry. Here, we first sought to determine if BM accumulation is a common feature of different arteries in T2DM, and second, to identify other effects of T2DM on the arterial proteome. METHODS: Human arterial samples collected during heart and vascular surgery from well-characterized patients and stored in the Odense Artery Biobank were analysed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We included ascending thoracic aortas (ATA) (n = 10 (type 2 DM, T2DM) and n = 10 (non-DM)); laser capture micro-dissected plaque- and media compartments from carotid plaques (n = 10 (T2DM) and n = 9 (non-DM)); and media- and adventitia compartments from ITAs (n = 9 (T2DM) and n = 7 (non-DM)). RESULTS: We first extended our previous finding of BM accumulation in arteries from T2DM patients, as 7 of 12 pre-defined BM proteins were significantly upregulated in bulk ATAs consisting of > 90% media. Although less pronounced, BM components tended to be upregulated in the media of ITAs from T2DM patients, but not in the neighbouring adventitia. Overall, we did not detect effects on BM proteins in carotid plaques or in the plaque-associated media. Instead, complement factors, an RNA-binding protein and fibrinogens appeared to be regulated in these tissues from T2DM patients. CONCLUSION: Our results suggest that accumulation of BM proteins is a general phenomenon in the medial layer of non-atherosclerotic arteries in patients with T2DM. Moreover, we identify additional T2DM-associated effects on the arterial proteome, which requires validation in future studies.

What to expect after open heart valve surgery? Changes in health-related quality of life.

PURPOSE: To (i) describe changes in health-related quality of life (HRQoL) pre-operatively, at discharge, and 4 weeks after discharge following open heart surgery, (ii) compare the performance of the EuroQol Questionnaire (EQ-5D 5L) and the Kansas City Cardiomyopathy Questionnaire (KCCQ) against an anchor-based approach, and to (iii) investigate the association between HRQoL and 180-day readmission. METHODS: A prospective, consecutive cohort (single-center study) of 291 patients completed the EQ-5D 5L and KCCQ pre-operatively, at discharge and 4 weeks post-discharge. Changes in HRQoL over time were evaluated, and the performance of the instruments was investigated. The association between HRQoL and readmission were investigated with Cox Proportional Hazard models. RESULTS: Scores of the EQ-5D Index and VAS decreased significantly from the pre-operative assessment to discharge and improved from discharge to 4 weeks after. The KCCQ scores significantly improved from baseline to 4 weeks after. Minimal clinically important improvements from before surgery to 4 weeks after were seen among 24% (EQ-5D Index), 45% (EQ-5D VAS), and 57% (KCCQ). More than one-third experienced worse HRQoL 1 month after discharge. Area under the curve (AUC) (performance of the instruments) demonstrated the following: EQ-5D Index AUC 0.622 (95% CI 0.540-0.704), VAS AUC 0.674 (95% CI 0.598-0.750), and KCCQ AUC 0.722 (95% CI 0.65-0.792). None of the HRQoL measurements were associated with 180-day readmission. CONCLUSIONS: This study revealed that HRQoL measured with the EQ-5D is significantly worse at discharge compared to before surgery, but scores increases within the first month measured with the EQ-5D and the KCCQ. The EQ-5D and KCCQ have a moderate correlation with an anchor-based approach but were not associated with readmission.

Experimental comparative study of a novel drug-eluting arteriovenous graft in a sheep model.

Background: Arteriovenous (AV) grafts often develop severe complications of stenosis due to neointimal proliferation that occurs either at the venous anastomosis site or at the outflow receiving vein. This study compares primary patency during 12 months of follow up for a new experimental Biomodics© interpenetrating polymer network (IPN) drug-eluting graft prototype with state-of-the-art GORE® ACUSEAL (ACUSEAL) in an AV graft model in sheep. Methods and results: An end-to-end bypass from the common carotid artery to the jugularis vein was performed bilaterally in 12 sheep. The usage of ACUSEAL or the IPN, both 6.0 mm in diameter, was determined via randomization. The sheep were followed up every 4 weeks with ultrasonic duplex scanning to determine patency; the experienced observer was blinded to the randomization. One sheep died after 11 days, and the final sample accordingly consisted of 11 animals. When comparing neointimal hyperplasia after 12 months in the two grafts, Fisher's exact test showed a significant difference with none out of 11 in the IPN grafts and 9 out of 11 in the ACUSEAL graft (p < 0.001). However, the Biomodics© IPN exhibited severe deterioration over time. Conclusions: Almost all of the grafts occluded during the 12 months of follow up. Although the zwitterion-bounded interpenetrating drug eluting polymer network showed signs to impair neointimal hyperplasia and thrombosis, age-related degeneration hindered demonstrating a potential improvement in patency.

Incidence and assessment of delirium following open cardiac surgery; A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis sought i) to provide an overview of the incidence of delirium following open cardiac surgery and ii) to investigate how incidences of delirium are associated with different assessment tools. METHODS AND RESULTS: A systematic search of studies investigating delirium following open cardiac surgery were conducted in Medline (Ovid), EMBASE, PsycINFO, CiNAHL and the Cochrane Database. Only studies with patients diagnosed or screened with a validated tool were included. Studies published from 2005 to 2021 were included in the meta-analysis.Of 7,126 individual studies retrieved, 106 met the inclusion criteria for the meta-analysis, hereof 31% of high quality. The weighted pooled incidence of delirium following open cardiac surgery across all studies was 23% (95% CI 20-26%), however we found a considerable heterogeneity (I2 = 99%), which could not be explained by subgroups or further sensitivity analyses. The most commonly applied screening tool for delirium is CAM/CAM-ICU. The lowest estimates of delirium were found by applying the Delirium Observation Scale (incidence 14%, 95% CI 8-20%), and the highest estimates in studies using "other" screening tools (Organic Brain Symptom Scale, Delirium Symptom Interview) pooled incidence of 43%, (95% CI 19 - 66%), however, only two studies applied these. CONCLUSION: Delirium following open cardiac surgery remains a complication with a high incidence of overall 23%, when applying a validated tool for screening or diagnosis. Nevertheless, this systematic review and meta-analyses highlight the significant inconsistency in current evidence regarding assessment tools and regimens. REGISTRATION: Prospero CRD42020215519.

Factors associated with deep sternal wound infection after open-heart surgery in a Danish registry.

Objective: To conduct a comprehensive multivariate analysis of variables associated with deep sternal wound infection, after open-heart surgery via median sternotomy. Method: A retrospective cohort of all adult patients, who underwent open-heart surgery at Odense University Hospital between 01-01-2000 and 31-12-2020 was extracted from the West Danish Heart Registry. Data were analyzed using maximum likelihood logistic regression. Results: A total of 15,424 patients underwent open-heart surgery and 244 developed a deep sternal wound infection, equivalent to 1,58 %. After data review 11,182 entries were included in the final analysis, of which 189 developed DSWI, equivalent to 1,69 %. Multivariate analysis found the following variables to be associated with the development of deep sternal wound infection (odds ratios and 95%confidens intervals in parentheses): Known arrhythmia (1.70; 1.16-2.44), Left Ventricular Ejection Fraction (1.66; 1.02-2.58), Body Mass Index 25-30 (1.66; 1.12-2.52), Body Mass Index 30-35 (2.35; 1.50-3.71), Body Mass Index 35-40 (3.61; 2.01-6.33), Body Mass Index 40+ (3.70; 1.03-10.20), Age 60-69 (1.64; 1.04-2.67), Age 70-79 (1.95; 1.23-3.19), Chronic Obstructive Pulmonary Disease (1.77; 1.21-2.54), Reoperation (1.63; 1.06-2.45), Blood transfusion in surgery (1.09; 1.01-1.17), Blood transfusion in intensive care unit (1.03; 1.01-1.06), Known peripheral atherosclerosis (1.82; 1.25-2.61), Current smoking (1.69; 1.20-2.35), Duration of intubation (1.33; 1.12-1.57). Conclusion: Increased risk of deep sternal wound infection after open-heart surgery is a multifactorial problem, while some variables are unchangeable others are not. Focus should be on optimizing the condition of the patient prior to surgery e.g. weight loss and smoking. But also factors surrounding the patient e.g. preventing blood loss and minimizing intubation time.

A targeted multiplex mass spectrometry method for quantitation of abundant matrix and cellular proteins in formalin-fixed paraffin embedded arterial tissue.

Assessment of proteins in formalin-fixed paraffin-embedded (FFPE) tissue traditionally hinges on immunohistochemistry and immunoblotting. These methods are far from optimal for quantitative studies and not suitable for large-scale testing of multiple protein panels. In this study, we developed and optimised a novel targeted isotope dilution mass spectrometry (MS)-based method for FFPE samples, designed to quantitate 17 matrix and cytosolic proteins abundantly present in arterial tissue. Our new method was developed on FFPE human tissue samples of the internal thoracic artery obtained from coronary artery bypass graft (CABG) operations. The workflow has a limit of 60 samples per day. Assay precision improved by normalisation to both beta-actin and smooth muscle actin with inter-assay coefficients of variation (CV) ranging from 5.3% to 31.9%. To demonstrate clinical utility of the assay we analysed 40 FFPE artery specimens from two groups of patients with or without type 2 diabetes. We observed increased levels of collagen type IV α1 and α2 in patients with diabetes. The assay is scalable for larger cohorts and advantageous for pathophysiological studies in diabetes and the method is easily convertible to analysis of other proteins in FFPE artery samples. SIGNIFICANCE: This article presents a novel robust and precise targeted mass spectrometry assay for relative quantitation of a panel of abundant matrix and cellular arterial proteins in archived formalin-fixed paraffin-embedded arterial samples. We demonstrate its utility in pathophysiological studies of cardiovascular disease in diabetes.

Atorvastatin and the influence on postoperative atrial fibrillation after surgical aortic valve replacement (STARC) in adults at Odense University Hospital, Denmark: study protocol for a randomised controlled trial.

INTRODUCTION: Atrial fibrillation (AF) is the most common postoperative complication after surgical aortic valve replacement (SAVR) and occurs in up to 50% of the patients. Development of postoperative AF (POAF) is associated with a 2-3 fold increased risk of adverse events, including stroke, myocardial infarction and death.Several studies have implied that prophylactic Atorvastatin therapy could prevent POAF in patients undergoing coronary artery bypass graft. These studies suggest that Atorvastatin has rapid and significant pleiotropic actions that reduce the risk of POAF. However, prophylactic treatment with statins has yet to be understood in SAVR. The aim of this study is to investigate whether prophylactic administration of torvastatin reduces POAF in patients undergoing SAVR. METHODS AND ANALYSIS: In this investigator-initiated, prospective, parallel-group, randomised, double-blind, placebo-controlled single-centre trial, 266 patients undergoing elective solitary SAVR with bioprosthetic valve, with no prior history of AF, and statin-naïve will be randomised (1:1) to treatment with Atorvastatin (80 mg once daily) or matching placebo for 1-2 weeks prior to and 30 days after surgery. The primary endpoint is POAF defined as an episode of irregular RR-intervals without a traceable p-wave of at least 30 s duration. After discharge and until day 30 after surgery, POAF will be documented by either rhythm strip or 12-lead ECG. ETHICS AND DISSEMINATION: Protocol approval has been obtained from the Regional Scientific Ethical Committee for Southern Denmark (S-20210159), The Danish Medicines Agency (2021103821) and the Data Protection Agency (21/65621).The trial is conducted in accordance with the Declaration of Helsinki, the ICH-GCP (International Conference on Harmonisation Good Clinical Practice) guidelines and the legal regulations of Denmark. Study findings will be shared via peer-reviewed journal publication and conference presentations. TRIAL REGISTRATION NUMBER: NCT05076019.

An Antibiotic-Loaded Silicone-Hydrogel Interpenetrating Polymer Network for the Prevention of Surgical Site Infections.

Surgical site infections (SSIs) are among the most frequent healthcare-associated infections, resulting in high morbidity, mortality, and cost. While correct hygiene measures and prophylactic antibiotics are effective in preventing SSIs, even in modern healthcare settings where recommended guidelines are strictly followed, SSIs persist as a considerable problem that has proven hard to solve. Surgical procedures involving the implantation of foreign bodies are particularly problematic due to the ability of microorganisms to adhere to and colonize the implanted material and form resilient biofilms. In these cases, SSIs may develop even months after implantation and can be difficult to treat once established. Locally applied antibiotics or specifically engineered implant materials with built-in antibiotic-release properties may prevent these complications and, ultimately, require fewer antibiotics compared to those that are systemically administered. In this study, we demonstrated an antimicrobial material concept with intended use in artificial vascular grafts. The material is a silicone-hydrogel interpenetrating polymer network developed earlier for drug-release catheters. In this study, we designed the material for permanent implantation and tested the drug-loading and drug-release properties of the material to prevent the growth of a typical causative pathogen of SSIs, Staphylococcus aureus. The novelty of this study is demonstrated through the antimicrobial properties of the material in vitro after loading it with an advantageous combination, minocycline and rifampicin, which subsequently showed superiority over the state-of-the-art (Propaten) artificial graft material in a large-animal study, using a novel porcine tissue-implantation model.

Early follow-up after open heart valve surgery reduces healthcare costs: a propensity matched study.

Objectives: The objective was to assess differences in healthcare costs within 180 days after discharge from open heart valve surgery in an intervention group receiving early, individualised and intensified follow-up compared with a historical control group. Methods: A cost-minimisation analysis comparing costs from a consecutive prospective cohort compared with a propensity matched cohort. Costs related to the intervention, hospital (outpatient visits and readmissions) and general practitioners (all contacts) were included. Data were obtained from electronic patient records and registry data. A logistic propensity model was used to identify the historical control group. Main results are presented as mean differences and 95% CIs based on bootstrapping. Results: After matching, the analysis included 300 patients from the intervention group and 580 controls. The mean intervention cost was €171 (SD 79) per patient. After 180 days, the mean healthcare costs were €1284 (SD 2567) for the intervention group and €2077 (SD 4773) for the controls. The cost of the intervention group was €793 (p<0.001) less per patient. The cost differences were explained mainly by fewer readmissions, fewer overall emergency visits and fewer contacts to the general practitioner during out-of-hours in the intervention group. Conclusions: The intervention consisting of early, individualised and intensified follow-up after open heart valve surgery significantly reduced the healthcare costs within 180 days after discharge.

Effect of early, individualised and intensified follow-up after open heart valve surgery on unplanned cardiac hospital readmissions and all-cause mortality.

BACKGROUND: Unplanned readmissions after heart valve surgery are common, and constitute a significant burden for the patient and the health care system. The objective was to investigate the effect of individualised follow-up after open heart valve surgery on a composite endpoint of first unplanned cardiac hospital readmission or all-cause mortality within 180 days of discharge. METHODS: The study is a prospective cohort study comparing the composite endpoint in patients undergoing early, individualised and intensified follow-up after heart valve surgery with a propensity matched historical control group. A total of 308 consecutive patients were enrolled in the prospective cohort study, 980 consecutive patients comprised the control group. The propensity matched group consisted of n = 300 (intervention) and n = 580 (controls). Time to first event was analysed using uni- and multivariable Cox proportional hazard analysis. Kaplan-Meier survival curves were constructed to assess the probability of survival without readmission. RESULTS: After 180 days, the proportion of patients experiencing the composite endpoint was significantly lower in the intervention group compared with the controls for the overall, unmatched population (23% vs. 38%; HR 0.55; 95% CI, 0.42 to 0.73; P < 0.001). The effect did not change in the propensity matched population (HR 0.57; 95% CI 0.43;0.75, P < 0.001). The difference was related to reduction in readmission rates, whereas death rates were similar in intervention and control group (1.6% vs. 1.8%). CONCLUSION: An intervention consisting of early, individualised and intensified follow-up after open heart valve surgery reduced the risk of a composite endpoint of first, unplanned cardiac hospital readmission or all-cause mortality within 180 days.

Data on an intervention to reduce readmissions after open heart valve surgery.

Data describe supplementary tables and figures related to the research article; Effect of early, individualised and intensified follow-up after open heart valve surgery on unplanned cardiac hospital readmissions and all-cause mortality [1]. Data on patients undergoing open heart valve surgery were presented in 308 patients in a prospective cohort and compared with 980 patients in a historical cohort. Included figures show inclusion and exclusion of patients (flowchart) and the specific elements of the intervention. Tables show causes of readmission and sensitivity analyses of differences among patients in the prospective intervention group compared with patients in the historical control group. Further results, interpretation and discussion of the included data can be found in the main research paper.