Temporal Cluster Analysis of Deep Sternal Wound Infection in a Regional Quality Collaborative.

INTRODUCTION: Deep sternal wound infection (DSWI) is a rare complication associated with high mortality. Seasonal variability in surgical site infections has been demonstrated, however, these patterns have not been applied to DSWI. The purpose of this study was to assess temporal clustering of DSWIs. METHODS: All cardiac surgery patients who underwent sternotomy were queried from a regional Society of Thoracic Surgeons database from 17 centers from 2001 to 2019. All patients with the diagnosis of DSWI were then identified. Cluster analysis was performed at varying time intervals (monthly, quarterly, and yearly) at the hospital and regional level. DSWI rates were calculated by year and month, and compared using mixed-effects negative binomial regression. RESULTS: A total of 134,959 patients underwent a sternotomy for cardiac surgery, of whom 469 (0.35%) developed a DSWI. Rates of DSWI per hospital across all years ranged from 0.12% to 0.69%. Collaborative-level rates of DSWIs were the greatest in September (0.44%) and the lowest in January (0.30%). Temporal clustering was not seen across seasonal quarters (high rate in preceeding quarter was not associated with a high rate in the next quarter) (P = 0.39). There were yearly differences across all institutions in the DSWI rates. A downward trend in DSWI rates was seen from 2001 to 2019 (P < 0.001). A difference among hospitals in the cohort was observed (P < 0.001). CONCLUSIONS: DSWI are a rare event within our region. Unlike other surgical site infection, there does not appear to be a seasonal pattern associated with DSWI.

Discordance among assays for monitoring? Anticoagulation during extracorporeal life support.

OBJECTIVES: The optimal method for monitoring of anticoagulation in patients on extracorporeal life support (ECLS) is unknown. The objective of this study was to assess the relationship between anti-factor Xa level (anti-Xa; IU/mL) and activated partial thromboplastin time (aPTT; seconds) for monitoring intravenous unfractionated heparin anticoagulation in adult ECLS patients. METHODS: Charts of all adult patients cannulated for ECLS from 2015 through 2017 were reviewed and laboratory and heparin infusion data were extracted for analysis. Time matched pairs of anti-Xa and aPTT were considered concordant if both laboratory values were within the same clinically utilized range. A hierarchical logistic regression model was used to determine factors associated with discordance while accounting for patient level effects. RESULTS: A total of 1016 paired anti-Xa and aPTT values from 65 patients were evaluated. 500 (49.2%) paired samples were discordant with a degree of variability on linear regression (r2 = 0.315). The aPTT fell into a higher therapeutic range compared to the anti-Xa in 31.6% and lower in 17.3%. Logistic regression demonstrated that discordance was independently associated with time from initiation of ECLS (OR 1.17 per day, p < 0.001), average heparin infusion rate (OR 1.25 per U/kg/hr, p < 0.001), and INR (OR 3.22, p < 0.001). CONCLUSIONS: Nearly half of all aPTT and anti-Xa values were in discordant ranges and discordance is more likely as the time on ECLS and the INR level increase. The use of either assay in isolation to guide heparin anticoagulation may lead to misestimation of the degree of anticoagulation in complex ECLS patients.

Genetic and Pharmacological Disruption of Interleukin-1α Leads to Augmented Murine Aortic Aneurysm.

BACKGROUND: Interleukin-1 (IL-1) signaling has an established role as a cytokine signaling pathway important for progression of abdominal aortic aneurysms (AAAs). While the IL-1ß ligand and IL-1R1 have been previously investigated, the role of the IL-1α ligand in AAAs remains unknown. In this study, we sought to examine the role of IL-1α in AAAs using genetic and pharmacologic approaches. METHODS: Eight-week-old wild-type (WT) or IL-1α knock-out (KO) male and female mice (n = 10-16/group) underwent experimental AAA and were harvested 14 days following surgery to assess AAA size and characteristics. In separate studies, 8-week-old WT mice were treated with an inhibitor to IL-1α during AAA formation and harvested 14 days following surgery. Finally, WT and IL-1α KO mice were administered Anakinra, an IL-R1 inhibitor, during AAA formation to determine the effect of inhibiting IL-1R1 when IL-1α is knocked out. RESULTS: Male and female IL-1α KO mice had larger AAAs compared to WT AAAs (male: 153% vs. 89.2%, P = 0.0001; female: 86.6% vs. 63.5%, P = 0.02). IL-1α KO mice had greater elastin breakage (P = 0.01), increased levels of macrophage staining (P = 0.0045), and greater pro-metallo proteinase 2 (P = 0.02). Pharmacologic inhibition of WT male mice with an IL-1α neutralizing antibody resulted in larger AAAs (133.1% vs. 77.0%, P < 0.001). Finally, treatment of IL-1α KO male mice with Anakinra decreased AAA formation compared with vehicle control AAAs (Anakinra + IL-1α KO: 47.7% vs. WT: 147.1%; P = 0.0001). CONCLUSIONS: IL-1α disruption using either genetic or pharmacologic approaches worsens AAAs.

Venoarterial Extracorporeal Life Support Use in Acute Pulmonary Embolism Shows Favorable Outcomes.

BACKGROUND: Differences in outcomes by indication for venoarterial extracorporeal life support (VA-ECLS) are poorly described. We hypothesized that patients on VA-ECLS for acute pulmonary embolism (PE) have fewer complications and better survival than patients on VA-ECLS for other indications. METHODS: All patients ≥18 years on VA-ECLS from the Extracorporeal Life Support Organization global registry (2010-2019) were evaluated (n = 29,842). After excluding patients aged >79 years (n = 729) and those with incomplete indication data (n = 2530), patients were stratified by VA-ECLS indication for PE vs all other indications. The association between being discharged alive and each type of complication with VA-ECLS indication was assessed. RESULTS: Of 26,583 patients included in the analysis, 978 (3.7%) were on VA-ECLS for a primary diagnosis of acute PE. Acute PE patients were younger (53.1 vs 56.7 years, P < .001) and were more likely to be women (52.1% vs 32.3%, P < .001). Patients who underwent VA-ECLS for acute PE were 78% more likely to be discharged alive vs patients supported with VA-ECLS for other reasons (52.8% vs 40.4%; P < .001). Acute PE patients had fewer cardiovascular and renal complications (26.6% vs 38.0% and 31.1% vs 39.4%, respectively; adjusted P < .001). Acute PE patients had higher odds of having clots and mechanical complications (8.7% vs 7.9% and 16.7% vs 14.6%, respectively; adjusted P < .001). CONCLUSIONS: Patients undergoing VA-ECLS for acute PE have higher odds of survival to hospital discharge compared with those supported for other indications. Additionally, VA-ECLS in this population is associated with fewer cardiovascular and renal complications but higher mechanical complications.

Influence of heart transplant allocation changes on hospital resource utilization.

Objectives: The 2018 change in the heart transplant allocation system resulted in greater use of temporary mechanical circulatory support. We hypothesized that the allocation change has increased hospital resource utilization, including length of stay and cost. Methods: All heart transplant patients within a regional Society of Thoracic Surgeons database were included (2012-2020). Patients were stratified before and after the transplant allocation changes into early (January 2012-September 2018) and late eras (November 2018-June 2020). Costs were adjusted for inflation and presented in 2020 dollars. Results: Of 535 heart transplants, there were 410 early and 125 late era patients. Baseline characteristics were similar, except for greater lung and valvular disease in the late era. Fewer patients in the late era were bridged with durable left ventricular assist devices (69% vs 31%; P < .0001), biventricular devices (5% vs 1%; P = .047), and more with temporary mechanical circulatory support (4% vs 46%; P < .0001). There was no difference in early mortality (6% vs 4%; P = .33) or major morbidity (57% vs 61%; P = .40). Length of stay was longer preoperatively (1 vs 9 days; P < .0001), but not different postoperatively. There was no difference in median total hospital cost ($132,465 vs $128,996; P = .15), although there was high variability. On multivariable regression, preoperative extracorporeal membrane oxygenation utilization was the main driver of resource utilization. Conclusions: The new heart transplant allocation system has resulted in different bridging techniques, with greater reliance on temporary mechanical circulatory support. Although this is associated with an increase in preoperative length of stay, it did not translate into increased hospital cost.

Socioeconomic Distress Associated With Increased Use of Percutaneous Coronary Intervention Over Coronary Artery Bypass Grafting.

BACKGROUND: The influence of socioeconomic determinants of health on choice of percutaneous coronary intervention (PCI) vs coronary artery bypass grafting (CABG) for coronary artery disease is unknown. We hypothesized that higher Distressed Communities Index (DCI) scores, a comprehensive socioeconomic ranking by zip code, would be associated with more frequent PCI. METHODS: All patients undergoing isolated CABG or PCI in a regional American College of Cardiology CathPCI registry and The Society of Thoracic Surgeons database (2018-2021) were assigned DCI scores (0 = no distress, 100 = severe distress) based on education level, poverty, unemployment, housing vacancies, median income, and business growth. Patients who presented with ST-segment elevation myocardial infarction or emergent procedures were excluded. The most distressed quintile (DCI ≥80) was compared with all other patients. Multivariable logistic regression analyzed the association between DCI and procedure type. RESULTS: A total of 23 223 patients underwent either PCI (n = 16 079) or CABG (n = 7144) for coronary artery disease across 28 centers during the study period. Before adjustment, high socioeconomic distress occurred more frequently among CABG patients (DCI ≥80, 12.4% vs 8.42%; P < .001). After multivariable adjustment, high socioeconomic distress was associated with greater odds of receiving PCI, relative to CABG (odds ratio 1.26; 95% CI, 1.07-1.49; P = .007). High socioeconomic distress was significantly associated with postprocedural mortality (odds ratio 1.52; 95% CI, 1.02-2.26; P = .039). CONCLUSIONS: High socioeconomic distress is associated with greater risk-adjusted odds of receiving PCI, relative to CABG, as well as higher postprocedural mortality. Targeted resource allocation in high DCI areas may help eliminate barriers to CABG.

Changes in Controllable Coronary Artery Bypass Grafting Practice for White and Black Americans.

BACKGROUND: Racial disparities in outcomes after cardiac surgery are well reported. We sought to determine whether variation by race exists in controllable practices during coronary artery bypass graft surgery (CABG). We hypothesized that racial disparities exist in CABG quality metrics, but have improved over time. METHODS: All patients undergoing isolated CABG (2000 to 2019) in a multiple state database were stratified into three eras by race. Analysis included propensity matched White Americans and Black Americans. Primary outcomes included left internal mammary artery use, multiple arterial grafting, revascularization completeness, and guideline-directed medication prescription. RESULTS: Of 72 248 patients undergoing CABG, Black American patients (n = 10 270, 15%) had higher rates of diabetes mellitus, hypertension, prior stroke, and myocardial infarction. After matching, 19 806 patients (n = 9903 per group) were well balanced. Left internal mammary artery use was significantly different early (era 1, Black Americans 84.7% vs White Americans 86.6%; P = .03), but equalized over time. Importantly, multiarterial grafting differed between Black Americans and White Americans over the entire study (9.1% vs 11.5%, P < .001) and within each era. Black Americans had more incomplete revascularization during the study period (14% vs 12.8%, P = .02) driven by a large disparity in era 1 (9.5% vs 7.2%, P < .001). Despite similar rates of preoperative use, Black Americans were more often discharged on a regimen of ß-blockers (91.8% vs 89.6%, P < .001). CONCLUSIONS: Coronary artery bypass graft surgery metrics of left internal mammary artery use and optimal medical therapy have improved over time and are similar despite patient race. Black Americans undergo less frequent multiarterial grafting and greater discharge ß-blocker prescription. Identifying changes in controllable CABG quality practices across races supports a continued focus on standardizing such efforts.

Donation frequency of blood donors participating in a prospective cohort study of iron status.

BACKGROUND: Blood centers are interested in understanding determinants of frequent blood donation. We hypothesized that participation in uncompensated research could result in higher donation rates. STUDY DESIGN AND METHODS: Donation rates for 2425 subjects from six US blood centers enrolled in the Retrovirus Epidemiology Donor Study-II Donor Iron Status Evaluation Study were compared to those of nonenrolled donors (n = 202,383). Over 15 months, we compared mean donation rates and adjusted rate ratios (RRs) between enrolled and nonenrolled for three subgroups, first-time, reactivated, and frequent donors, and donation rates before and after the study enrollment period for frequent donors only. RESULTS: Enrolled donors had higher 15-month mean donation rates than nonenrolled donors (first-time, 1.21 [RR = 1.91]; reactivated, 1.68 [RR = 1.83]; frequent, 3.40 [RR = 1.12]). However, frequent donors donated at approximately the same rate after enrollment as they did before enrollment in the study (3.62 per 15 months [RR = 1.12]). CONCLUSION: Donors enrolled in the study donated at a higher rate than nonenrolled donors, but frequent donors remained consistent in their donation frequency both before and after enrollment. Although increased donation rates could have been causally related to study enrollment, we cannot rule out an enrollment bias whereby more committed donors were more likely to enroll in the study.

Surgical versus transcatheter mitral valve replacement in functional mitral valve regurgitation.

Surgical mitral valve intervention for severe functional, or secondary mitral regurgitation is a viable option for patients deemed to be operative candidates and can be performed via traditional sternotomy or by minimally invasive techniques with similar outcomes. Transcatheter mitral valve replacement is an emerging technology with a potential role in the treatment of functional mitral valve regurgitation. A plethora of devices are currently in development and in various stages of clinical investigation. Operative approach to transcatheter mitral valve replacement varies from a percutaneous transseptal approach to a hybrid percutaneous/surgical apical approach. The Tendyne, Intrepid and Evoque systems show promising results from their early feasibility studies in treatment of patients with mitral regurgitation that were too high risk for surgery. In this review, we describe considerations for surgical and transcatheter mitral valve replacement for functional mitral valve regurgitation.

Towards chronic deep brain stimulation in freely moving hemiparkinsonian rats: applicability and functionality of a fully implantable stimulation system.

Objective.This study aimed at investigating a novel fully implantable deep brain stimulation (DBS) system and its ability to modulate brain metabolism and behavior through subthalamic nucleus (STN) stimulation in a hemiparkinsonian rat model.Approach.Twelve male rats were unilaterally lesioned with 6-hydroxydopamine in the medial forebrain bundle and received a fully implantable DBS system aiming at the ipsilesional STN. Each rat underwent three cylinder tests to analyze front paw use: a PRE test before any surgical intervention, an OFF test after surgery but before stimulation onset and an ON test under DBS. To visualize brain glucose metabolism in the awake animal, two [18F]FDG scans were conducted in the OFF and ON condition. At least 4 weeks after surgery, an [18F]FDOPA scan was used to check for dopaminergic integrity.Main results.In general, STN DBS increased [18F]FDG uptake ipsilesionally and decreased it contralesionally. More specifically, bilateral orbitofrontal cortex, ipsilateral caudate putamen, sensorimotor cortex and nucleus accumbens showed significantly higher tracer uptake in ON compared to OFF condition. Contralateral cingulate and secondary motor cortex, caudate putamen, amygdala, hippocampus, retrosplenial granular cortex, superior colliculus, and parts of the cerebellum exhibited significantly higher [18F]FDG uptake in the OFF condition. On the behavioral level, stimulation was able improve use of the contralesional affected front paw suggesting an effective stimulation produced by the implanted system.Significance.The fully implantable stimulation system developed by us and presented here offers the output of arbitrary user-defined waveforms, patterns and stimulation settings and allows tracer accumulation in freely moving animals. It is therefore a suitable device for implementing behavioral PET studies. It contributes immensely to the possibilities to characterize and unveil the effects and mechanisms of DBS offering valuable clues for future improvements of this therapy.

The Risk and Reward of Speaking Out for Racial Equity in Surgical Training.

In order to maintain productivity and career advancement, Black and Brown individuals often find themselves downplaying persistent elements of bias and racism experienced in predominantly white fields. These elements are commonly reinforced by institutional and departmental policies that hinder the creation of an equitable and inclusive environment for all. In this manuscript, we outline specific challenges faced by Black and Brown trainees and faculty that are perpetuated by such policies. The challenges are followed by specific recommendations for change as they may apply to faculty, staff and trainees. The outlined recommendations or "action items" may be enacted by any residency program or department based on perceived timeliness and should serve as a foundation for change-one that is intently created through a lens of anti-racism. The risk of speaking up for racial equity is outweighed by the potential rewards of building an environment that is diverse, inclusive and better for everyone.

Biospecimen repositories: are blood donors willing to participate?

BACKGROUND: Sponsored by the National Heart, Lung, and Blood Institute, the Retrovirus Epidemiology Donor Studies (REDS-I/-II) have conducted epidemiologic, laboratory, and survey research on volunteer blood donors. Some studies request additional permission to store biospecimens for future studies. The representativeness and applicability of studies performed using repositories may be reduced by low participation rates. STUDY DESIGN AND METHODS: Demographics from subjects consenting to participate in the 2007 REDS-II Leukocyte Antibodies Prevalence Study (LAPS) repository were compared to "study-only" subjects. Data from the 1998 REDS-I survey of donor opinion regarding storage and use of biospecimens were also explored. RESULTS: Overall, 91% of LAPS subjects agreed to participate in the repository. Odds of repository participation were lower among African American and Hispanic donors, 35- to 44-year-olds, donors who had not completed high school, and donors from one geographic location, regardless of other variables. Survey data from 1998 revealed that 97% of respondents approved of long-term storage of biospecimens, although only 87% indicated that they would personally participate. Many respondents would require notification or their permission be obtained before participation. Minority respondents would require permission or notification more often and were less certain they would personally participate in a repository. CONCLUSION: Blood donors are quite willing to participate in biospecimen repositories. Regional differences and lower odds of participation in the minority blood donor population may result in a reduced number of biospecimens available for study and a decreased ability to definitely answer specific research questions in these populations.

Enhanced Recovery After Thoracic Surgery.

Enhanced recovery pathways (ERPs), used across multiple surgical subspecialties, is a multidisciplinary delivery of perioperative care designed to lessen the psychological stress of patients undergoing surgery. Thoracic ERP has been implemented but is not widespread, and variations exist between programs. Evidence of the benefit of thoracic ERP is emerging. This article presents common components of a thoracic surgery ERP and reviews contemporary outcomes.

Evaluation and comparison of coagulation factor activity in fresh-frozen plasma and 24-hour plasma at thaw and after 120 hours of 1 to 6°C storage.

BACKGROUND: Current transfusion-related acute lung injury reduction strategies include avoiding transfusion of plasma products collected from female donors or female donors that have been pregnant to reduce transfusion of plasma-containing HLA antibodies. Such a policy considerably decreases the number of donors available for generation of fresh-frozen plasma (FFP). To increase the supply of FFP, substitution of 24-hour plasma (FP24) and thawed plasma (TP) derived from either FFP or FP24 may be viable substitutes. To justify such a policy the coagulation factor content of FFP, FP24, and TP derived from both product types was assessed. STUDY DESIGN AND METHODS: Coagulation factor (F)II, FV, FVII, FVIII, F IX, and FX; protein C (PC) and protein S (PS); von Willebrand factor antigen and ristocetin cofactor; fibrinogen; and antithrombin activities were analyzed in nonpaired FFP and FP24 at the time of product thaw and again after 120 hours of 1 to 6°C storage. RESULTS: At thaw, mean FVIII and PC activities were lower in FP24 than FFP. Mean PC and PS activities were lower in FP24- than FFP-derived 120-hour-old TP. No other differences in mean activity reached significance. Activity levels were generally lower in TP; FVIII, FV, and FVII showed the largest changes. However, prestorage leukoreduction appears to improve the stability of FV. CONCLUSION: FFP, FP24, and the derived TP all contain adequate coagulation factor activities to maintain hemostatic activity. As FFP becomes less available, increased use of FP24 and TP are viable alternatives for most clinical situations.

Porcine Model of Infrarenal Abdominal Aortic Aneurysm.

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called ß-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease. Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone. Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% ± 47.4% at day 7, 105.4% ± 58.1% at day 14, and 113.5% ± 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p < 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease. Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN.

An integrated, accurate, rapid, and economical handheld consumer gluten detector.

Celiac disease, characterized by autoimmune reactions to dietary gluten, affects up to 3 million in the US and approximately 0.5%-1% globally. A strict, lifelong gluten-free diet is the only treatment. An economic, simple, accurate, rapid and portable gluten testing device would enable gluten-sensitive individuals to safeguard their food safety. We developed a novel solution, Nima™, a gluten sensor that integrates food processing, gluten detection, result interpretation and data transmission in a portable device, detecting gluten proteins at or below the accepted 20 ppm threshold. We developed specific monoclonal antibodies, an optimized lateral flow immunoassay strip, and one-step aqueous extraction. Compared with reference R5, NimaTM antibodies (13F6 and 14G11) had 35- and 6.6-fold higher gliadin affinities, respectively. We demonstrated device performance using a comprehensive list of foods, assessing detection sensitivity, reproducibility, and cross-reactivity. Nima™ presented a 99.0% true positive rate, with a 95% confidence interval of 97.8%-100%.

Predicting charge-times of implantable cardioverter defibrillators.

A novel method of validation of the mathematical model for batteries that power Medtronic's Implantable Cardioverter Defibrillators (ICDs) is presented. In a conventional approach used in the past, the model has been validated against data collected in controlled laboratory conditions. To supplement this approach, we now validate the model against ICD performance data reported from devices used in the field for periods ranging from about five to seven years. The key model output is ICD "charge time" - the time required to charge a high voltage capacitor in preparation to deliver shock to the heart. This validation is carried out for five of Medtronic's ICD designs and very close agreement is obtained between model predictions and field data.

Comparison and stability of ADAMTS13 activity in therapeutic plasma products.

BACKGROUND: The von Willebrand factor (VWF)-cleaving protease, ADAMTS13, is often deficient in cases of thrombotic thrombocytopenic purpura (TTP). The primary treatment of TTP is therapeutic plasma exchange (TPE) utilizing a variety of plasma products that help restore ADAMTS13 activity. However, multiple replacement products are available to choose from. Thawed plasma products have a variable refrigerated shelf life depending on the product type; stability of ADAMTS13 in thawed products stored at 1 to 6 degrees C has not been determined. STUDY DESIGN AND METHODS: ADAMTS13 activity was measured in three types of plasma products and cryoprecipitate. Fresh-frozen plasma (FFP) aliquots and cryoprecipitate-poor plasma (CPP) products were produced from 10 whole-blood (WB) donations. Twenty-four-hour plasma products were manufactured from 10 additional WB donations. ADAMTS13 activity in these products at time of thaw and after 5 days of storage at 1 to 6 degrees C was measured with a modified version of the FRETS-VWF73 fluorogenic assay. ADAMTS13 activity at time of thaw was measured in 10 units of cryoprecipitate and five related CPP products. RESULTS: ADAMTS13 is present in similar amounts in FFP, CPP, and 24-hour plasma products. Storage at 1 to 6 degrees C for up to 5 days did not significantly diminish ADAMTS13 activity. The concentration of ADAMTS13 in cryoprecipitate was significantly higher than that observed in plasma products. CONCLUSION: FFP, CPP, and 24-hour plasma products should be equally effective for ADAMTS13 restoration through TPE and should remain so for the duration of the shelf life of the thawed products.