How I manage differential gas exchange in peripheral venoarterial extracorporeal membrane oxygenation.

Dual circulation is a common but underrecognized physiological occurrence associated with peripheral venoarterial extracorporeal membrane oxygenation (ECMO). Competitive flow will develop between blood ejected from the heart and blood travelling retrograde within the aorta from the ECMO reinfusion cannula. The intersection of these two competitive flows is referred to as the "mixing point". The location of this mixing point, which depends upon the relative strengths of the native and extracorporeal pumps, will determine which regions of the body are perfused with blood ejected from the left ventricle and which regions are perfused by reinfused blood from the ECMO circuit, effectively establishing dual circulations. Because gas exchange within these circulations is dictated by the native lungs and membrane lung, respectively, oxygenation and carbon dioxide removal may differ between regions-depending on how well gas exchange is preserved within each circulation-potentially leading to differential oxygenation or differential carbon dioxide, each of which may have important clinical implications. In this perspective, we address the identification and management of dual circulation and differential gas exchange through various clinical scenarios of venoarterial ECMO. Recognition of dual circulation, proper monitoring for differential gas exchange, and understanding the various strategies to resolve differential oxygenation and carbon dioxide may allow for more optimal patient management and improved clinical outcomes.

2021: Perioperative and critical care year in review for the cardiothoracic surgery team.

For yet another year, our lives have been dominated by a pandemic. This year in review, we feature an expert panel opinion regarding extracorporeal support in the context of COVID-19, challenging previously held standards. We also feature survey results assessing the impact of the pandemic on cardiac surgical volume. Furthermore, we focus on a single center experience that evaluated the use of pulmonary artery catheters and the comparison of transfusion strategies in the Restrictive and Liberal Transfusion Strategies in Patients With Acute Myocardial Infarction (REALITY) trial. Additionally, we address the impact of acute kidney injury on cardiac surgery and highlight the controversy regarding the choice of fluid resuscitation. We close with an evaluation of dysphagia in cardiac surgery and the impact of prehabilitation to optimize surgical outcomes.

Technical Aspects of Lung Volume Reduction Surgery Including Anesthetic Management and Surgical Approaches.

As palliative treatment, lung volume reduction surgery can be offered to a selected subset of chronic obstructive pulmonary disease patients. Careful adherence to established inclusion and exclusion criteria is critical to achieve good outcomes. The evolution of surgical techniques toward minimally invasive approaches has improved outcomes. The fully extrathoracic access combining a subxiphoid incision with subcostal port placement allowed a further decrease in perioperative pain, which favors spontaneous respiratory drive and early postoperative mobilization. Less aggressive resections and better match for size of the hemithorax have contributed to a short-term reduction in morbidity and continued improvements in cardiopulmonary function.

Uniportal Video-Assisted Transcervical Thymectomy.

Surgery has proven superiority over medical management for patients with nonthymomatous myasthenia gravis. The key is complete resection of the gland, which can be achieved with various techniques. The uniportal video-assisted transcervical technique allows minimally invasive surgery with a low complication rate, a good cosmetic result, and a short length of recovery.

IL-17A and IL-2-expanded regulatory T cells cooperate to inhibit Th1-mediated rejection of MHC II disparate skin grafts.

Several evidences suggest that regulatory T cells (Treg) promote Th17 differentiation. Based on this hypothesis, we tested the effect of IL-17A neutralization in a model of skin transplantation in which long-term graft survival depends on a strong in vivo Treg expansion induced by transient exogenous IL-2 administration. As expected, IL-2 supplementation prevented rejection of MHC class II disparate skin allografts but, surprisingly, not in IL-17A-deficient recipients. We attested that IL-17A was not required for IL-2-mediated Treg expansion, intragraft recruitment or suppressive capacities. Instead, IL-17A prevented allograft rejection by inhibiting Th1 alloreactivity independently of Tregs. Indeed, T-bet expression of naive alloreactive CD4+ T cells and the subsequent Th1 immune response was significantly enhanced in IL-17A deficient mice. Our results illustrate for the first time a protective role of IL-17A in CD4+-mediated allograft rejection process.

IL-17A mediates early post-transplant lesions after heterotopic trachea allotransplantation in Mice.

Primary graft dysfunction (PGD) and bronchiolitis obliterans (BO) are the leading causes of morbidity and mortality after lung transplantation. Reports from clinical and rodent models suggest the implication of IL-17A in either PGD or BO. We took advantage of the heterotopic trachea transplantation model in mice to study the direct role of IL-17A in post-transplant airway lesions. Across full MHC barrier, early lesions were controlled in IL-17A(-/-) or anti-IL17 treated recipients. In contrast, IL-17A deficiency did not prevent subsequent obliterative airway disease (OAD). Interestingly, this early protection occurred also in syngeneic grafts and was accompanied by a decrease in cellular stress, as attested by lower HSP70 mRNA levels, suggesting the involvement of IL-17A in ischemia-reperfusion injury (IRI). Furthermore, persistence of multipotent CK14(+) epithelial stem cells underlined allograft protection afforded by IL-17A deficiency or neutralisation. Recipient-derived γδ(+) and CD4(+) T cells were the major source of IL-17A. However, lesions still occurred in the absence of each subset, suggesting a high redundancy between the innate and adaptive IL-17A producing cells. Notably, a double depletion significantly diminished lesions. In conclusion, this work implicated IL-17A as mediator of early post-transplant airway lesions and could be considered as a potential therapeutic target in clinical transplantation.

Critical role of regulatory T cells in Th17-mediated minor antigen-disparate rejection.

Th17-mediated immune responses have been recently identified as novel pathogenic mechanisms in a variety of conditions; however, their importance in allograft rejection processes is still debated. In this paper, we searched for MHC or minor Ag disparate models of skin graft rejection in which Th17 immune responses might be involved. We found that T cell-derived IL-17 is critical for spontaneous rejection of minor but not major Ag-mismatched skin grafts. IL-17 neutralization was associated with a lack of neutrophil infiltration and neutrophil depletion delayed rejection, suggesting neutrophils as an effector mechanism downstream of Th17 cells. Regulatory T cells (Tregs) appeared to be involved in Th17 reactivity. We found that in vivo Treg depletion prevented IL-17 production by recipient T cells. An adoptive cotransfer of Tregs with naive monospecific antidonor T cells in lymphopenic hosts biased the immune response toward Th17. Finally, we observed that IL-6 was central for balancing Tregs and Th17 cells as demonstrated by the prevention of Th17 differentiation, the enhanced Treg/Th17 ratio, and a net impact of rejection blockade in the absence of IL-6. In conclusion, the ability of Tregs to promote the Th17/neutrophil-mediated pathway of rejection that we have described should be considered as a potential drawback of Treg-based cell therapy.