Complications Associated with Catheter Ablation of Atrial Fibrillation in Current Practice: Insights from a Large, Real-World Collaboration

Background: Catheter ablation is a cornerstone treatment for symptomatic atrial fibrillation (AF) with major improvements in safety over time. However, rates of adverse events with use of current techniques in a contemporary quality-focused network remain undefined. Objective(s): Across a large, real-world sample, we sought to describe (1) rates of major, adverse events associated with catheter ablation of AF and (2) patient-level factors associated with complications. Method(s): Utilizing the REAL-AF collaboration, a registry of contemporary AF ablation procedures with granular patient, procedural and follow-up data comprised of cases from over 50 operators across academic and non-academic sites, we evaluated all patients undergoing their first ablation procedure from January 2018 - June 2022. Risk-adjusted analyses were conducted to evaluate the relationship between patient factors and complications. Result(s): Among 3144 patients (age 66.1 +/- 11.0 years, 42% female, 67.1% paroxysmal, 32.9% persistent) who underwent AF ablation, procedure-related complications (n =77) were identified in 65 patients (2.1%) with multiple complications occurring in 9 patients (0.2%). Most complications (n=70, 93.5%) occurred in the peri-procedural (within 30 days) period and 6.5% (n=5) after 30 days, the latter of which all represented vascular injuries (Figure). Major complications (18 of 72 peri-procedural complications, 25.0%) are defined, detailed, and associated data reported in the Figure. Unadjusted (16.0% without CHF vs. 33.3% with CHF, p = 0.045) and risk-adjusted (OR 2.8, 95% CI 1.03-7.60, p=0.045) analyses indicated history of CHF was associated with a composite outcome of major complications. Analyses of independent complications showed those who suffered from peri-procedural stroke (n=3) were of significantly greater age (77.3 +/- 5.5 years vs. 66.1 +/- 10.9 years, p=0.035). Risk-adjusted analyses showed history of vascular disease (OR 2.9, 95% CI 1.02-8.20, p=0.045) was associated with vascular injury (n=18). From 0-695 days post-procedure, 31 deaths occurred (unknown cause: 17, COVID-19 related: 4, heart failure: 2, cardiac arrest: 2). Conclusion(s): Major complications represent rare events among those undergoing AF ablation in current practice. Risk-adjusted analyses suggest a history of CHF is associated with major complications. Similarly, older age and a history of vascular disease are associated with stroke and vascular complications, respectively. [Formula presented]Copyright © 2023

Multifactorial Effects of Covid-19: A Review of Published Autopsy Reports

Introduction: SARS-CoV-2 is responsible for the current global pandemic. SARS-CoV-2 infection underlies the novel viral condition coronavirus disease 2019 (COVID-19). COVID-19 causes significant pulmonary sequelae contributing to serious morbidities. The pathogenesis of COVID-19 is complex with a multitude of factors leading to varying levels of injury numerous extrapulmonary organs. This review of 124 published articles documenting COVID- 19 autopsies included 1,142 patients. Method(s): A PubMed search was conducted for COVID-19 autopsy reports published before March 2021 utilizing the query COVID-19 Autopsy. There was no restriction regarding age, sex, or ethnicity of the patients. Duplicate cases were excluded. Findings were listed by organ system from articles that met selection criteria. Result(s): Pulmonary pathology (72% of articles;866/1142 patients): diffuse alveolar damage (563/866), alveolar edema (251/866), hyaline membrane formation (234/866), type II pneumocyte hyperplasia (165/866), alveolar hemorrhage (164/866), and lymphocytic infiltrate (87/866). Vascular pathology (41% of articles;771/1142 patients): vascular thrombi (439/771)-microvascular predominance (294/439)-and inflammatory cell infiltrates (116/771). Cardiac pathology (41% of articles;502/1142 patients): cardiac inflammation (186/502), fibrosis (131/502), cardiomegaly (100/502), hypertrophy (100/502), and dilation (35/502). Hepatic pathology (33% of articles;407/1142 patients): steatosis (106/402) and congestion (102/402). Renal pathology (30% of articles;427/1142 patients): renal arteries arteriosclerosis (111/427), sepsis-associated acute kidney injury (81/427) and acute tubular necrosis (77/427). Conclusion(s): This review revealed anticipated pulmonary pathology, along with significant extrapulmonary involvement secondary to COVID-19, indicating widespread viral tropism throughout the human body. These diverse effects require additional comprehensive longitudinal studies to characterize short-term and long-term COVID-19 sequelae and inform COVID-19 treatment.

Depression in patients with cerebral microangiopathy.

Cerebral microangiopathy (CMA) is one of the significant causes of depression in the elderly. Close associations of the risk of developing depression with white matter hyperintensity, the presence of lacunar infarcts, and other markers of vascular disease are shown. The available data suggest that various vascular mechanisms, in particular, involvement of small vessels of the brain, generalized microvascular and endothelial dysfunction, metabolic risk factors, - are risk factors for the development of depression. Pathogenetic mechanisms include cerebral hypoperfusion and immune dysregulation. Depression is also a common complication of coronavirus infection, occurring both in the acute and post-COVID periods. The same mechanisms as in vascular depression are involved in the pathogenesis of the development of post-COVID depressive disorders. Given the complexity of the mechanisms of development of depressive disorders in patients with CMA, the presence of severe comorbid vascular pathology, antidepressants with an optimal ratio of efficacy and safety should be preferred. Agomelatine (Valdoxan) is one of such drugs.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

Repurposing Metformin for Vascular Disease.

Metformin has seen use as an oral anti-hyperglycaemic drug since the late 1950s; however, following the release in 1998 of the findings of the 20-year United Kingdom Prospective Diabetes Study (UKPDS) metformin use rapidly increased and today is the first-choice anti-hyperglycaemic drug for patients with type 2 diabetes (T2D). Metformin is in daily use by an estimated 150 million people worldwide. Historically, the benefits of metformin as an anti-diabetic and cardiovascular-protective drug have been linked to effects in the liver, where it acts to inhibit gluconeogenesis and lipogenesis, as well as reducing insulin resistance and enhancing peripheral glucose utilization. However, direct protective effects on the endothelium and effects in the gut prior to metformin absorption are now recognized as being important. In the gut, metformin modulates the glucagon-like peptide-1 (GLP-1)- gut-brain axis as well as impacting the intestinal microbiota. As the apparent number of putative tissue and cellular targets for metformin has increased, so has interest in re-purposing metformin to treat other diseases that include polycystic ovary syndrome (PCOS), cancer, neurodegenerative diseases and COVID-19. Metformin is also being investigated as an anti-ageing drug. Of particular interest is whether metformin provides the same level of vascular protection in individuals other than those with T2D, including obese individuals with metabolic syndrome, or in the setting of vascular thromboinflammation caused by SARS-CoV-2. In this review we critically evaluate the literature to highlight clinical settings in which metformin might be therapeutically repurposed for the prevention and treatment of vascular disease.

The metabolic effects of APOL1 in humans.

Harboring apolipoprotein L1 (APOL1) variants coded by the G1 or G2 alleles of the APOL1 gene increases the risk for collapsing glomerulopathy, focal segmental glomerulosclerosis, albuminuria, chronic kidney disease, and accelerated kidney function decline towards end-stage kidney disease. However, most subjects carrying APOL1 variants do not develop the kidney phenotype unless a second clinical condition adds to the genotype, indicating that modifying factors modulate the genotype-phenotype correlation. Subjects with an APOL1 high-risk genotype are more likely to develop essential hypertension or obesity, suggesting that carriers of APOL1 risk variants experience more pronounced insulin resistance compared to noncarriers. Likewise, arterionephrosclerosis (the pathological correlate of hypertension-associated nephropathy) and glomerulomegaly take place among carriers of APOL1 risk variants, and these pathological changes are also present in conditions associated with insulin resistance, such as essential hypertension, aging, and diabetes. Insulin resistance may contribute to the clinical features associated with the APOL1 high-risk genotype. Unlike carriers of wild-type APOL1, bearers of APOL1 variants show impaired formation of lipid droplets, which may contribute to inducing insulin resistance. Nascent lipid droplets normally detach from the endoplasmic reticulum into the cytoplasm, although the proteins that enable this process remain to be fully defined. Wild-type APOL1 is located in the lipid droplet, whereas mutated APOL1 remains sited at the endoplasmic reticulum, suggesting that normal APOL1 may participate in lipid droplet biogenesis. The defective formation of lipid droplets is associated with insulin resistance, which in turn may modulate the clinical phenotype present in carriers of APOL1 risk variants.

Treatment of diseases through stem cell bioengineering techniques

The development of stem cell transplantation technology has opened up the possibility of curing many diseases that were difficult to treat in the past. There are ethical issues in the field of widespread clinical use of human embryonic stem cells, and tissue rejection may also occurs after transplantation. One way to solve these problems is to generate specific pluripotent stem cells directly from patient cells to study specific treatments. Induced stem cells refer to a type of cell produced by the reprogramming of human somatic cells into exogenous transcription factors, which are very similar to embryonic stem cells. Both types of cells express human pluripotent factors and embryonic stem cell surface markers, and have the potential to differentiate into 3 germ layers.The induced pluripotent stem cells can be induced to differentiate into different cells under different conditions. At present, stem cell therapy has entered the clinical trial stage in many fields, and this paper discusses the stem cell regenerative medicine in the field of cardiovascular disease, eye disease, and COVID-19. This paper is a review of the current status of stem cell treatment and the challenges it is facing. © 2023 SPIE.

From acute SARS-CoV-2 infection to pulmonary hypertension.

As the world progressively recovers from the acute stages of the coronavirus disease 2019 (COVID-19) pandemic, we may be facing new challenges regarding the long-term consequences of COVID-19. Accumulating evidence suggests that pulmonary vascular thickening may be specifically associated with COVID-19, implying a potential tropism of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus for the pulmonary vasculature. Genetic alterations that may influence the severity of COVID-19 are similar to genetic drivers of pulmonary arterial hypertension. The pathobiology of the COVID-19-induced pulmonary vasculopathy shares many features (such as medial hypertrophy and smooth muscle cell proliferation) with that of pulmonary arterial hypertension. In addition, the presence of microthrombi in the lung vessels of individuals with COVID-19 during the acute phase, may predispose these subjects to the development of chronic thromboembolic pulmonary hypertension. These similarities raise the intriguing question of whether pulmonary hypertension (PH) may be a long-term sequela of SARS-COV-2 infection. Accumulating evidence indeed support the notion that SARS-COV-2 infection is indeed a risk factor for persistent pulmonary vascular defects and subsequent PH development, and this could become a major public health issue in the future given the large number of individuals infected by SARS-COV-2 worldwide. Long-term studies assessing the risk of developing chronic pulmonary vascular lesions following COVID-19 infection is of great interest for both basic and clinical research and may inform on the best long-term management of survivors.

Respiratory function and symptoms after acute COVID-19 infection in children and adolescents

Introduction/Aim: Significant long-term effects on both symptomatology and respiratory function have been recognised in adult populations after COVID-19 infection, termed 'Long COVID'. These have caused loss of productivity and increased need for healthcare services. This study aimed to measure symptoms and lung function in children and adolescents after acute COVID-19 infection Methods: Between June 1 and 31 October 2021 there were 144 children admitted to hospital across the Sydney Children's Hospital Network, Australia. Of these, 63 children were referred to the respiratory clinic with symptoms of ongoing cough, shortness of breath and fatigue, 3-6 months post COVID infection. 20 of these children performed reliable lung function. For these children, body plethysmography and double diffusion testing were performed within 3-6 months of their infection. The Liverpool respiratory questionnaire and PROMIS paediatric sleep questionnaires were also administered. Result(s): Of the 20 patients tested, 7 had COVID pneumonitis requiring hospitalisation during the acute illness. 6 of the 20 patients had significant persistent symptoms as measured by the Liverpool respiratory questionnaire, while none of the children had any significant sleep symptoms. All children had preserved spirometry within normal limits. Of note, 2 children with persistent respiratory symptoms had DLNO/DLCO ratio >1.15, suggesting pulmonary vascular disease. The same two children who had elevated DLNO / DLCO had high ventilator equivalents on CPET testing suggesting increased physiological dead space ventilation. Despite this, their peak aerobic capacity was within normal limits. There were no significant differences between the alpha and delta cohorts or between children treated at home vs those requiring hospitalisation during their infection. Conclusion(s): COVID-19 may cause long-lasting effects in children. In this cohort, all children maintained spirometry results within normal limits despite significant symptoms impacting daily activities. Double diffusion testing may shed some light on lung changes leading to persistent symptomatology after COVID infection.

BASELINE AND TEMPORAL DIFFERENCES IN PROTEOMICS FOLLOWING SARS-CoV-2 INFECTION IN PWH

Background: COVID-19 may be more severe in persons with HIV (PWH). However, underlying biological mechanisms associated with the development of COVID-19 and its clinical severity among antiretroviral therapy (ART) treated PWH are largely unknown. Therefore, we wished to evaluate temporal changes in plasma proteins following SARS-CoV-2 infection and identify pre-infection proteomic markers associated with future COVID-19. Method(s): We analyzed the data of clinical, antibody-confirmed COVID-19 ARTtreated PWH from the global Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE). Individuals were matched on geographic region, age, and sample timing to antibody-negative controls. For cases and controls, pre-COVID-19 pandemic specimens were obtained prior to January 2020 to assess temporal changes and baseline differences in protein expression in relationship to COVID-19 severity, using mixed effects models adjusted for false-discovery rate. Result(s): We compared 257 unique plasma proteins (Olink Proteomics) in 94 COVID-19 antibody-confirmed clinical cases and 113 matched antibody-negative controls, excluding COVID-19 vaccinated participants (median age 50 years, 73% male). 40% of cases were characterized as mild;60% moderate to severe. Median time from COVID-19 infection to follow-up sampling was 4 months. Temporal changes in protein expression differed based on COVID-19 disease severity. Among moderate to severe cases vs. controls, NOS3 increased, whereas ANG, CASP-8, CD5, GZMH, GZMB, ITGB2, and KLRD1 decreased. Higher baseline circulating concentrations of granzymes A, B and H (GZMA, GZMB and GZMH) were associated with the future development of moderate-severe COVID-19 in PWH and were related to immune function, including CD4, CD8 and the CD4/ CD8 ratio. Conclusion(s): We identified temporal changes in novel proteins in closely linked inflammatory, immune, and fibrotic pathways which may relate to COVID-19-related morbidity among ART-treated PWH. Further, we identified key granzyme proteins, serine proteases expressed by cytotoxic T lymphocytes and NK cells in response to foreign antigens, associated with future COVID-19 in PWH. Our results provide unique insights into the biological susceptibility and responses to COVID-19 infection in PWH. (Figure Presented).

Simultaneous systemic thrombosis as a manifestation of COVID-19.

BACKGROUND: The current COVID-19 pandemic mainly affects the respiratory system;however, with the increase in cases worldwide, there is evidence of compromise at the cardiovascular level, which can manifest as acute myocardial infarction, myocarditis, pericarditis, myopericarditis, heart failure, cardiogenic shock, vasculitis, deep vein thrombosis, pulmonary embolism, ischemic stroke, acute arterial insufficiency, arrhythmias, and sudden death. CLINICAL CASE: A 70-year-old male patient who simultaneously presented multisystemic thrombosis manifested by cerebral vascular event, pulmonary thromboembolism, acute myocardial infarction and acute arterial insufficiency in the context of SARSCoV-2 pneumonia. CONCLUSION(S): In patients with COVID-19 there is a high thrombogenic potential secondary to blood stasis, hypercoagulability and endothelial dysfunction, which worsens the prognosis and increases mortality, mainly in patients who require ICU stay, so an adequate thromboprophylactic or anticoagulant scheme and follow-up in the convalescent phase must be provided to detect sequelae associated with COVID-19.Copyright © 2022 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.

Prevalence of adverse drug reactions associated with emergency department visits and risk factors for hospitalization

Objective: Adverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. Method(s): Observational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Result(s): 10,799 patients visited the emergency department and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 +/- 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24, 95% CI: 1.47-7.13, p = 0.003, in Charlson comorbidity index 4-6;and aOR 20.07, 95% CI: 6.87-58.64, p = 0.000, in Charlson comorbidity index >= 10). Conclusion(s): The prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.Copyright © 2022 Sociedad Espanola de Farmacia Hospitalaria (S.E.F.H)

Application of Neoaortoiliac System For Contained Rupture of Mycotic Infrarenal Aortic Aneurysm

Funding: None. Synopsis: 61-year-old male who initially presented to an outside facility with streptococcal pneumoniae meningitis and bacteremia. Of note, he had history of COVID-19 pneumonia a month prior. On hospital day 15, he reported sudden onset lower back pain prompting imaging which demonstrated a contained rupture of an infrarenal aortic aneurysm that had significantly evolved in comparison to admission imaging where his infrarenal aorta had the largest dimension measuring 2.9cm. We present the successful application of neoaortoiliac system (NAIS). Method(s): Proceeding with midline laparotomy we encountered dense adhesive disease due to his history of surgery for colon cancer. After adhesiolysis, we exposed the aorta and aneurysm with severe surrounding inflammatory changes. 20cm of femoral vein was harvested, reversed, and joined for a span of 4cm using an Endo GIA 45mm vascular load to create our neoaorta. Proximal and distal clamp zones were developed. Upon entering the aneurysm, a foul smell was encountered, revealing that the noxious process had destroyed the posterior wall of the aorta and paraspinal tissues. Our neoaorta was anastomosed in end-to-end fashion to the infrarenal aorta and subsequently to the common iliac arteries. Flow was initially restored to the hypogastric arteries and then the external iliac arteries. The retroperitoneum was closed over our repair and covered with omentum. Result(s): On post-operative day 2, he had hematochezia;intraoperatively, the IMA was noted to be 1mm in size, though had brisk back-bleeding and was ultimately ligated. A flexible sigmoidoscopy revealed ischemic sloughing of the sigmoid colon near his previous anastomosis from his colon cancer resection though no transmural necrosis. He remains on high-dose ceftriaxone to complete a 6-week course and metronidazole for 10 days due to his sigmoid mucosal ischemia per infectious disease recommendations. He is now post-operative day 10 and remains in the ICU. Conclusion(s): Mycotic aortic aneurysms constitute 1-1.8% of aortic aneurysms. The standard of treatment is aggressive debridement of involved aortic wall and periaortic tissue, in-situ or extra-anatomic reconstruction, coverage with an omental flap and long-term antibiotic therapy. NAIS is resistant to infection and aneurysmal dilation, however, is a time-consuming procedure with a mean completion time of 8 hours. Dorweiler et al. demonstrated that vascular reconstruction with femoral vein in infected aortoiliofemoral fields has a mortality of 9-10% with negligible rate of late complications (graft stenosis, thrombosis, and dilation) and that venous morbidity after femoral vein harvest is well tolerated. Clagett et al. demonstrated that NAIS fashioned from greater saphenous vein had a failure rate requiring intervention of 64% compared to 0% for those constructed with deep femoral vein. Lastly, it is important to note that our patient was previously COVID-19 positive. This case demonstrates that the sequela of COVID-19 may have been a significant factor in our patient's pathophysiology. As we continue to learn about the effects of COVID-19 on vascular pathology, we must keep a large repertoire of operative techniques at hand in order to treat complex presentations of vascular emergencies. [Formula presented] [Formula presented] [Formula presented] Institution: Orlando Health, Orlando, FLCopyright © 2022

Comorbidities Associated With Myocarditis In Hospitalized COVID-19 Patients

Introduction: While COVID-19 is predominantly a lung infection, it can cause systemic viremia in susceptible patients and lead to cardiac involvement and myocarditis (MC);an inflammation of the myocardium characterized by arrhythmias, cardiogenic shock, acute heart failure, and death. Although rare, there is evidence of a surge in MC-related admissions during the COVID-19 pandemic, implying a correlation. However, the risk factors associated with MC susceptibility in these patients remain unclear. This study aims to assess the comorbidities and demographic features associated with the development of MC in adult patients with COVID-19. Method(s): Data were obtained from the PearlDiver database (PearlDiver Technologies, Fort Wayne, IN). The database provides all-payers administrative claims data on the patient level. Using ICD-10-CM codes, a cohort of patients hospitalized with a primary diagnosis of COVID-19 was identified. The study included only patients admitted to the hospital between January and October 2020 to minimize bias associated with vaccine-related MC. Within this cohort, patients diagnosed with MC during and up to one month after admission were identified and their demographic features and comorbidities to were compared to those without MC. We calculated Risk Ratios with their respective 95% CI. A p-value <0.05 was deemed significant. Result(s): We found 627,465 admissions due to COVID-19 from January to October 2020, with 506 (0.08 %) diagnosis of MC. Patients with MC were more likely to be males (60%), younger (mean age 48, SD= 23 vs. 60, SD =17 - p<0.01), and they had more comorbidities (mean Elixhauser Comorbidity Index: 7.52, SD= 5 vs. 6.9, SD = 5 - p<0.001). The development of MC was significantly associated with a history of coagulopathies [0.55(0.46-0.66);p<0.0001], asthma [1.20 (1.06-1.23);p= 0.01], deep venous thrombosis [1.54(1.38-1.68);p<0.0001], renal disease[1.15 (1.02-1.27);p= 0.03], congestive heart failure [1.24 (1.12-1.34);p=0.006], ischemic heart disease [1.25 (1.14-1.35);p=0.0001], and arrhythmias [1.24 (1.14-1.32);p< 0.0001]. However, a history of diabetes [0.89 (0.67-0.99);p=0.02], hypertension [0.71 (0.62-0.80);<0.000.1], depression [0.71(0.52-0.88);p=0.0001], and hypothyroidism [0.42(0.08-0.69);p<0.0001] was associated with lower risk of MC-related hospitalization. Other preexistent conditions including, psychosis, rheumatoid arthritis, cerebrovascular disease, obesity, tobacco use, alcohol abuse, HIV, anemia, peripheral vascular disease, and non-metastatic solid tumor were not significantly correlated with MC. Discussion(s): MC is a rare yet serious complication of COVID-19. Therefore, a better knowledge of the pathophysiology of COVID-19 and the patient factors associated with development to MC is crucial for prognostication and providing risk-adjusted treatment. Conclusion(s): Patients with a history of cardiovascular disease, renal and pulmonary disease were more likely to develop MC as a result of COVID-19. However, hypertension and diabetes were associated with lower risk of MC, which warrants further investigation.Copyright © 2022

The Importance of Simulation in Vascular Training: A Literature Review

Funding: None. Synopsis: Once a subspecialty of general surgery, vascular surgery has transitioned to an entity with its own training paradigms and board certification. Part of this transition is due to many advances in technology, devices, and techniques. The management of vascular pathology that was at one time relegated to open procedures has now shifted to a field where endovascular options can be performed. These advances come with the concern of training competent vascular surgeons who are already under stringent duty hours restrictions, deal with heightened scrutiny associated with patient safety, and recently have had their operative volumes decreased due to COVID-19-related cancellations and shut downs. Simulation has been offered as a possible means to mitigate these limitations and shift the learning curve to competency. Despite this, little is known regarding the efficacy and best practices of incorporating simulation into vascular training. Method(s): A literature review was performed of English language articles on the EBSCO database without publication date restrictions on vascular surgery simulation. Search terms included vascular surgery simulation, endovascular surgery simulation and vascular education simulation. Additional studies were found by searching reference lists of relevant articles. All study designs were included if they pertained to simulation for open vascular or endovascular procedures. Simulator fidelity, educational efficacy, validity of the simulator, transfer of skill, and cost and time effectiveness were assessed. With endovascular simulation we assessed the amount of handling error, procedure time, fluoroscopy time, and the amount of contrast used. Result(s): Using these methods, twenty-two articles were identified. In regards to simulation used for open procedures in vascular surgery, the analysis showed that the most important factors in determining efficacy were the involvement of expert level (attending) proctors and the use of high fidelity (cadaver) simulators. Other important determinants were the use of trainee-specific models and the employment of specific learning objectives. The use of virtual endovascular simulators in enhancing trainee competence is supported by better quality data in the literature. Specifically measured and proven outcomes are a decrease in catheter handling errors, a reduction in both procedure and fluoroscopy time, and a diminished volume of contrast used. Endovascular simulators also allowed for reliable and consistent assessment of operator performance and showed a good transfer of skill to actual cases. Conclusion(s): Simulation is an important tool for both the assessment and training of vascular residents. The use of expert proctors, appropriate simulators, and well-designed curricula are the keys to success. Further studies connecting simulation training to patient-centered outcomes are still needed to define the true potential of these tools and methods. Institution: Lousiana State University HSC, New Orleans, LACopyright © 2022

Constructing custom-made radiotranscriptomic signatures from CT angiograms: An application in COVID-19 vascular inflammation

Background: Advances in computational methodologies have enabled processing of large datasets originating from imaging studies. However, most imaging biomarkers suffer from a lack of direct links with underlying biology, as they are only observationally correlated with pathophysiology. Purpose(s): To develop and validate a novel AI-assisted image analysis platform, by applying quantitative radiotranscriptomics that quantifies cytokinedriven vascular inflammation from routine CT angiograms (CTA) performed as part of clinical care in COVID-19. Method(s): We used this platform to train the radiotranscriptomic signature C19-RS, derived from the perivascular space around the aorta and the internal mammary artery in routine chest CTAs, to best describe cytokinedriven vascular inflammation, defined using transcriptomic profiles from RNA sequencing data from human arterial biopsies (A). This signature was validated externally in 358 clinically indicated CT pulmonary angiograms from patients with or without COVID-19 from 3 different geographical regions. Result(s): First, 22 patients who had a CTA before the pandemic underwent repeat CTA <6 months post COVID-19 infection (B). Compared with 22 controls (matched for age, gender, and BMI) C19-RS was increased only in the COVID-19 group (C). Next, C19-RS was calculated in a cohort of 331 patients hospitalised during the pandemic, and was higher in COVID-19 positives (adjusted OR=2.97 [95% CI: 1.43-6.27], p=0.004, D). C19-RS had prognostic value for in-hospital mortality in COVID-19, with HR=3.31 ([95% CI: 1.49-7.33], p=0.003) and 2.58 ([95% CI: 1.10-6.05], p=0.028) in two testing cohorts respectively (E, F), adjusted for clinical factors and biochemical biomarkers of inflammation and myocardial injury. The corrected HR for in-hospital mortality was 8.24 [95% CI: 2.16-31.36], p=0.002 for those who received no treatment with dexamethasone, but only 2.27 [95% CI: 0.69-7.55], p=0.18 in those who received dexamethasone subsequently to the C19-RS based image analysis, suggesting that vascular inflammation may have been a therapeutic target of dexamethasone in COVID-19. Finally, C19-RS was strongly associated (r=0.61, p=0.0003) with a whole blood transcriptional module representing dysregulation of coagulation and platelet aggregation pathways. Conclusion(s): We present the first proof of concept study that combines transcriptomics with radiomics to provide a platform for the development of machine learning derived radiotranscriptomics analysis of routine clinical CT scans for the development of non-invasive imaging biomarkers. Application in COVID-19 produced C19-RS, a marker of cytokine-driven inflammation driving systemic activation of coagulation, that predicts inhospital mortality and identifies people who will have better response to anti-inflammatory treatments, allowing targeted therapy. This AI-assisted image analysis platform may have applications across a wide range of vascular diseases, from infections to autoimmune diseases.

Propensity-Matched Comparison of Robotic-Assisted Pulmonary Lobectomy Outcomes in Pre-COVID-19 Patients versus COVID-19-Era Patients

INTRODUCTION: The COVID-19 pandemic has presented patients with barriers to receiving healthcare. We sought to determine whether changes in healthcare access and practice during the COVID-19 pandemic has affected perioperative outcomes after robotic-assisted pulmonary lobectomy (RAPL). METHOD(S): We retrospectively analyzed 721 consecutive patients who underwent RAPL between September 2010 and March 2022 by one surgeon at one institution. With March 1st, 2020, defining the start of the COVID-19 pandemic, we grouped 638 patients as PreCOVID-19 and 83 patients as COVID-19-Era based on surgical date. An optimal variable ratio matching method of one to four PreCOVID-19 patients (with average of three) were matched to each COVID-19-Era patient. Variables used for matching were age, gender, smoking history in pack-years, and preoperative diabetes mellitus, coronary artery disease or myocardial infarction, and FEV1%. Variables of interest were compared utilizing Student's t-test, Wilcoxon rank-sum test, and Chi-square (or Fisher's exact) test, with significance at p<=0.05. Multivariable generalized linear regression was used to investigate predictors of the presence of postoperative complications and report odds ratios (OR). RESULT(S): COVID-19-Era patients had higher incidences of preoperative atrial fibrillation (p=0.027), peripheral vascular disease (p=0.0425), and pancreatitis (p=0.0349) compared to PreCOVID-19 patients. Differences in tumor size and histology, nodal status, and AJCC v8 pathologic stage were statistically insignificant. COVID-19-Era patients experienced a high incidence of effusion or empyema postoperatively (p< 0.0001). The PreCOVID-19 and COVID-19-Era cohorts had comparable odds for developing a postoperative complication. Older age, longer intraoperative skin-to-skin duration, and preoperative COPD are all predictive of an increased risk of developing a postoperative complication (Table 1). CONCLUSION(S): Despite our COVID-19-Era patients having greater indices of preoperative comorbidities, our analysis showed that they had a similar risk of developing a postoperative complication when compared to our PreCOVID-19 patients. Risk factors for development of postoperative effusion should be determined to minimize risk of empyema in COVID-19-Era patients. Patient age, skin-to-skin duration of the procedure, and preoperative COPD should be considered when planning for complication risk following RAPL.

Glutamine Deficiency Promotes Immune and Endothelial Cell Dysfunction in COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has caused the death of almost 7 million people worldwide. While vaccinations and new antiviral drugs have greatly reduced the number of COVID-19 cases, there remains a need for additional therapeutic strategies to combat this deadly disease. Accumulating clinical data have discovered a deficiency of circulating glutamine in patients with COVID-19 that associates with disease severity. Glutamine is a semi-essential amino acid that is metabolized to a plethora of metabolites that serve as central modulators of immune and endothelial cell function. A majority of glutamine is metabolized to glutamate and ammonia by the mitochondrial enzyme glutaminase (GLS). Notably, GLS activity is upregulated in COVID-19, favoring the catabolism of glutamine. This disturbance in glutamine metabolism may provoke immune and endothelial cell dysfunction that contributes to the development of severe infection, inflammation, oxidative stress, vasospasm, and coagulopathy, which leads to vascular occlusion, multi-organ failure, and death. Strategies that restore the plasma concentration of glutamine, its metabolites, and/or its downstream effectors, in conjunction with antiviral drugs, represent a promising therapeutic approach that may restore immune and endothelial cell function and prevent the development of occlusive vascular disease in patients stricken with COVID-19.

The outcome of pulmonary function tests and high-resolution computed tomography of chest in post-coronavirus disease 2019-confirmed cases after 3 months of recovery

Background: Coronavirus disease (COVID-19) is a recently prevalent infectious disease that is caused by a virus from the coronavirus family and causes acute respiratory syndrome. It is a pandemic catastrophe that has affected more than 60 million people around the world and has caused about 1.5 million deaths, as reported by the WHO. This disease affects the respiratory system and leads to different forms of symptoms and signs. Pneumonia is a common cause for hospitalization, with most patients treated in hospital wards and others requiring ICU. Although the number of complete recoveries from COVID-19 has increased, there is still concern about complications associated with the disease that appear after recovery. The studies that have looked at past types and other forms of coronavirus epidemics, such as SARS have shown that some cases had respiratory complications from the infection after being full recovered, as 36 and 30% of the entire study population had clinical and high-resolution computed tomography (HRCT) changes at 3 and 6 months after recovery, respectively. Mostly, the abnormalities seen in pulmonary function test (PFT) results are sequelae of diffusion capacity defect. In recovered cases of Middle East respiratory syndrome, 36% of patients showed HRCT sequelae at follow-up of 6 weeks, because of fibrosis. Data on COVID-19 indicate that prolonged disease and persistent symptoms show post-PFT affection and follow-up radiographic changes after recovery from COVID-19 as interstitial pulmonary changes and a degree of pulmonary vasculopathy. In recovered cases of COVID-19, capacity of diffusion is the commonest defect in lung function, followed by the restrictive pattern defects on spirometry;both are related to the degree of severity of pneumonic COVID-19. PFTs (involving spirometry as well as diffusion capacity) are considered as routine follow-up examinations for some of the recovered cases, especially severe cases. Rehabilitation programs of the respiratory system are an option strategy that might be considered. This study aims to show changes in pulmonary function and HRCT of chest in post-COVID-19-infected patients to detect long-term effects on the lungs after 3 months as obstructive or restrictive, or both, lung diseases. Patients and Methods: The study was conducted on 100 confirmed PCR-positive COVID-19 cases that were admitted to Ain Shams University Isolation Hospitals, and the follow-up was performed in the outpatient clinic. PCR samples (Combined nasopharyngeal and oropharyngeal swab) were taken after 3 months from discharge of patients above the age of 18 years who become negative with clinical improvement. PFT [spirometry and diffusion for carbon monoxide (DLCO)] and chest HRCT were done. All patients' clinical data were recorded, and CT chest imaging data of these patients were correlated with the clinical data. Result(s): A total of 100 patients were included in this study, where males represented 58% and female represented 42%. The mean+/-SD age of cases in this study was 45.05 +/- 11.80 years and ranged from 20 to 79 years. CT chest severity score (SS) of abnormality in COVID-19-infectedd patients based on HRCT chest findings before and after 3 months from treatment showed a highly significant correlation (P=0.000). The results of PFT in the studied group after 3 months of discharge showed restrictive pattern in 14.9%, obstructive pattern in 17.8%, and both obstructive and restrictive patterns in 5.9% of the total number of cases. There was a significant correlation between DLCO abnormality findings and age of studied group (P=0.032), a significant correlation between abnormality findings on PFT and HRCT chest SS after discharge of the studied group (P0.001). There was a significant correlation between abnormality findings of DLCO and HRCT chest SS after 3 months of the studied group (P=0.000) and before treatment (P=0.001), whereas there was no significant correlation between other findings of PFT and HRCT chest SS after 3 months and before. There was a significant correlation between H

Temporal Trend in Mortality from Covid-19 Associated with Cardiovascular Disease

Background Coronavirus disease 2019 (COVID-19) mortality remains high in those with cardiovascular disease (CVD). The temporal trend in higher COVID-19 mortality due to CVD has public health implications. We assessed the association between CVD and COVID-19 mortality throughout the COVID-19 pandemic. Methods We retrospectively studied all patients who received care for COVID-19 at Rush University System for Health during the pandemic (divided into 7 waves based on predominant virus variants and vaccine rollouts). CVD was defined as congestive heart failure (CHF), myocardial infarction (MI), cerebrovascular or peripheral vascular disease (ascertained by ICD codes). Using multivariable logistic regression, we assessed independent associations of COVID-19 mortality with age, sex, race, and 17 comorbidities in the Charlson comorbidity index, overall and stratified by pandemic waves. Results Of 43876 patients (mean age 40, 56% female, 14% with CVD), 1032 (2%) died from COVID-19 between March 2020 and August 2022. Adjusted for covariables, mortality was 3.2 times as likely in those with CVD as those without (OR=3.2, 95%CI 2.7-3.9;p<0.001). There was a trend toward increasing mortality associated with co-existing CVD as pandemic progressed to later waves (where Delta and Omicron were predominant), particularly in those with CHF or MI (Figure). Conclusion We found that COVID-19 mortality associated with co-existing CVD (particularly CHF and MI) increased temporally throughout the pandemic. [Formula presented]Copyright © 2023 American College of Cardiology Foundation