Aortic arch rupture in a patient with Marfan syndrome and previous aortic root repair: A stepwise approach to intraoperative catastrophe.

Marfan syndrome (MS) is an autosomal dominant connective tissue disease associated with significant morbidity and mortality due to progressive dilatation of the thoracic aorta which can lead to aortic rupture. Survival from an aortic rupture is predicated on immediate organized and goal directed care by both surgical and anesthesia teams. This case highlights how coordinated care from a cardiac operating room team, including early preparation of autologous blood products, expeditious placement of intravascular access for rapid high volume transfusion, and intentional communication between anesthesia, perfusion, surgery and nursing during the resuscitation in the OR, can all lead to an improved outcome.

Prevention of postoperative atrial fibrillation in cardiac surgery: a quality improvement project.

PURPOSE: Postoperative atrial fibrillation (POAF) has an incidence of 20-60% in cardiac surgery. The Society of Cardiovascular Anesthesiologists and the European Association of Cardiothoracic Anaesthesiology Practice Advisory have recommended postoperative beta blockers and amiodarone for the prevention of POAF. By employing quality improvement (QI) strategies, we sought to increase the use of these agents and to reduce the incidence of POAF among our patients undergoing cardiac surgery. METHODS: This single-centre QI initiative followed the traditional Plan, Do, Study, Act (PDSA) cycle scientific methodology. A POAF risk score was developed to categorize all patients undergoing cardiac surgery as either normal or elevated risk. Risk stratification was incorporated into a preprinted prescribing guide, which recommended postoperative beta blockade for all patients and a postoperative amiodarone protocol for patients with elevated risk starting on postoperative day one (POD1). A longitudinal audit of all patients undergoing cardiac surgery was conducted over 11 months to track the use of prophylactic medications and the incidence of POAF. RESULTS: Five hundred and sixty patients undergoing surgery were included in the QI initiative from 1 December 2020 to 1 November 2021. The baseline rate of POAF across all surgical subtypes was 39% (198/560). The use of prophylactic amiodarone in high-risk patients increased from 13% (1/8) at the start of the project to 41% (48/116) at the end of the audit period. The percentage of patients receiving a beta blocker on POD1 did fluctuate, but remained essentially unchanged throughout the audit (34.8% in December 2020 vs 46.7% in October 2021). After 11 months, the overall incidence of POAF was 29% (24.9% relative reduction). Notable reductions in the incidence of POAF were observed in more complex surgical subtypes by the end of the audit, including multiple valve replacement (89% vs 56%), aortic repair (50% vs 33%), and mitral valve surgery (45% vs 33%). CONCLUSIONS: This single-centre QI intervention increased the use of prophylactic amiodarone by 28% for patients at elevated risk of POAF, with no change in the early postoperative initiation of beta blockers (46.7% of patients by POD1). There was a notable reduction in the incidence of POAF in patients at elevated risk undergoing surgery.

RéSUMé: OBJECTIF: Il y a une incidence de 20 à 60 % de fibrillation auriculaire postopératoire (FAPO) en chirurgie cardiaque. Dans un avis de pratique, la Society of Cardiovascular Anesthesiologists et l'European Association of Cardiothoracic Anaesthesiology ont recommandé l'utilisation de bêtabloquants et d'amiodarone en postopératoire pour la prévention du FAPO. En employant des stratégies d'amélioration de la qualité (AQ), nous avons cherché à augmenter l'utilisation de ces agents et à réduire l'incidence de FAPO chez nos patient·es bénéficiant d'une chirurgie cardiaque. MéTHODE: Cette initiative d'AQ monocentrique a suivi la méthodologie scientifique traditionnelle du cycle Plan, Do, Study, Act (PDSA), soit Planifier, Réaliser, Étudier, Agir. Un score de risque de FAPO a été mis au point pour catégoriser toute la patientèle bénéficiant d'une chirurgie cardiaque comme présentant un risque normal ou élevé. La stratification du risque a été intégrée dans un guide de prescription préimprimé, qui recommandait des bêtabloquants en période postopératoire pour tou·tes les patient·es et un protocole postopératoire d'amiodarone pour celles et ceux présentant un risque élevé et débutant à partir du premier jour postopératoire (JPO1). Une vérification longitudinale de toute la patientèle bénéficiant d'une chirurgie cardiaque a été menée sur une période de 11 mois afin de suivre l'utilisation de médicaments prophylactiques et l'incidence de FAPO. RéSULTATS: Cinq cent soixante personnes opérées ont été incluses dans l'initiative d'AQ entre le 1er décembre 2020 et le 1er novembre 2021. Le taux initial de FAPO pour tous les sous-types chirurgicaux était de 39 % (198/560). L'utilisation d'amiodarone prophylactique chez les patient·es à risque élevé est passée de 13 % (1/8) au début du projet à 41 % (48/116) à la fin de la période de vérification. Le pourcentage de patient·es recevant un bêtabloquant au JPO1 a fluctué, mais est resté fondamentalement inchangé tout au long de la période de vérification (34,8 % en décembre 2020 vs 46,7 % en octobre 2021). Après 11 mois, l'incidence globale de FAPO était de 29 % (réduction relative de 24,9 %). Des réductions notables de l'incidence de FAPO ont été observées dans des sous-types chirurgicaux plus complexes à la fin de la vérification, y compris le remplacement de plusieurs valves (89 % vs 56 %), la réparation aortique (50 % vs 33 %) et la chirurgie valvulaire mitrale (45 % vs 33 %). CONCLUSION: Cette intervention monocentrique d'amélioration de la qualité a augmenté l'utilisation de l'amiodarone prophylactique de 28 % chez les patient·es présentant un risque élevé de FAPO, sans changement dans l'amorce postopératoire précoce des bêtabloquants (46,7 % des patient·es au JPO1). Il y a eu une réduction notable de l'incidence de FAPO chez les patient·es à risque élevé bénéficiant d'une intervention chirurgicale.

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

Rationale and design of the colchicine for the prevention of perioperative atrial fibrillation in patients undergoing major noncardiac thoracic surgery (COP-AF) trial.

BACKGROUND: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. METHODS AND RESULTS: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023. CONCLUSIONS: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery.

Assessing the Benefits of Preoperative Thoracic Epidural Placement for Lung Transplantation.

OBJECTIVE: The authors investigated the effect of preoperative thoracic epidural (PreTE) catheter placement versus not placing a preoperative thoracic epidural catheter (NoPreTE) on the duration of postoperative ventilation time, time to become coherent (measured as time to become Confusion Assessment Method-intensive care unit [ICU] negative), opioid consumption, ICU length of stay (LOS), and hospital LOS. DESIGN: Retrospective cohort design. SETTING: Single institution, university hospital. PARTICIPANTS: Patients undergoing lung transplantation. COMPARISON GROUPS: PreTE group was defined as patients who received a thoracic epidural preoperatively. NoPreTE group was defined as patients who either received a thoracic epidural postoperatively or who did not receive a thoracic epidural postoperatively. MEASUREMENTS AND MAIN RESULTS: Fifty-six patients for the PreTE and 99 for NoPreTE groups were included in the study. After a excluding patients with postoperative ventilation times greater than 96 hours, preoperative thoracic epidural was associated with shorter time on the ventilator (19.1 hours v 30.6 hours; p < 0.001), time to become coherent (26.4 hours v 37.6 hours; p = 0.008), ICU LOS (6.4 days v 12.4 days; p = 0.018), and hospital LOS (15.9 days v 23.5 days; p = 0.04) compared to patients who did not receive a preoperative epidural. After controlling for single versus double lung transplantation and duration of cardiopulmonary bypass (CPB), differences in time to become coherent, ICU LOS, and hospital LOS became nonsignificant. Opioid consumption was significantly higher in those patients who did not receive a preoperative epidural. Despite a high rate of anticoagulation for CPB (89.5%), no neurologic complications or epidural hematomas were observed. CONCLUSION: For those lung transplant patients ventilated for less than 96 hours postoperatively, preoperative thoracic epidural placement is associated with shorter postoperative ventilator time and reduced opioid consumption. Time to become coherent postoperatively, ICU LOS, and hospital LOS also improved in this cohort, though the significance decreased after adjusting for possible confounders. A larger prospective study is necessary to confirm if timing of thoracic epidural placement alters time to become coherent postoperatively and ICU LOS.

Thoracoscopic wedge resection of the lung using high-frequency jet ventilation in a postpneumonectomy patient.

A 61-year-old female ex-smoker presented with a suspicious right lower lobe mass after previously undergoing a left pneumonectomy. Due to the peripheral nature of the lung lesion, a right thoracoscopic wedge resection was proposed by the surgical team. Adequate ventilation, oxygenation, and surgical conditions were obtained using high-frequency jet ventilation to the operative lung throughout the procedure. The trachea was extubated in the operating room, and the patient recovered uneventfully from the procedure. This case demonstrates the feasibility of limited thoracoscopic lung resections postpneumonectomy with the use of high-frequency jet ventilation.

Metastatic ductal eccrine adenocarcinoma masquerading as an invasive ductal carcinoma of the male breast.

We report the case of a 38-year-old man with metastatic ductal eccrine adenocarcinoma (DEA) of the left breast responding to 5-flourouracil, epirubicin and cyclophosphamide (FEC) chemotherapy. He initially presented with a 2-week history of difficulty walking because of bilateral hip and lower back pain. Examination showed an ulcerating cutaneous mass over the left anterior chest wall, left axillary lymphadenopathy and tenderness over the spine. A punch biopsy of the breast lesion resulted in a diagnosis of metastatic invasive ductal carcinoma (IDC) of the breast. He received palliative radiotherapy to the spine and also received six cycles of FEC chemotherapy and was subsequently commenced on tamoxifen and ibandronate. There was a symptomatic and radiological response to the FEC chemotherapy. Referral was subsequently made to our institution where the original punch biopsy was reviewed. This showed tumor cells that were polygonal with darkly stained pleomorphic nuclei and abundant eosinophilic cytoplasm and were also localized to areas of fibrotic stroma containing eccrine glands and ducts but did not appear to involve mammary tissue. Immunohistochemical studies showed the tumors to be cytokeratin 7 and gross cystic disease fluid protein-15/prolactin inducible protein negative and estrogen receptor alpha positive. Both the morphological and the immunohistochemical characteristics of the tumor were consistent with a revised diagnosis of DEA rather than IDC. When last reviewed, the patient remains pain free and his disease stable 17 months after his original presentation. This case emphasizes the challenge in discriminating histopathologically between two rare tumors of the male breast, namely DEA and IDC. In addition, clinical response to FEC by metastatic DEA has not been previously documented, and this therapeutic regimen warrants further investigation.

Imatinib binding and cKIT inhibition is abrogated by the cKIT kinase domain I missense mutation Val654Ala.

Several activating mutations in the cKIT receptor tyrosine kinase are associated with the development and progression of gastrointestinal stromal tumors (GIST). Treatment of GIST with the tyrosine kinase inhibitor imatinib (Gleevec, STI571; Novartis, Basel, Switzerland) increases patient survival. However, many patients develop resistance to imatinib following initial responses. We sequenced cKIT exons from two patients with GIST after the development of imatinib resistance, revealing a point mutation in kinase domain I (exon 13), Val654Ala, which has been associated previously with relapse and resistance. Molecular modeling of cKIT-imatinib complexes shows that this residue is located in the drug-binding site and that the Val654Ala mutation disrupts drug binding by removing hydrophobic contacts with the central diaminophenyl ring of imatinib. Loss of these contacts results in a destabilizing effect on two key hydrogen bonds between imatinib and Asp310 and Thr670 of cKIT. Calculations based on published crystallography data show an estimated destabilization energy of 2.25 kcal/mol in the Val654Ala cKIT compared with wild type. When present on the same cKIT allele as an oncogenic mutation, the Val654Ala mutation abolishes imatinib-mediated inhibition of cKIT phosphoactivation in vitro. These results highlight some of the structural and functional consequences of the Val654Ala mutation in relapsing imatinib-resistant GIST and emphasize the importance of tumor genetics in drug development and patient-specific cancer treatment regimens.