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Background: Enhanced recovery after surgery (ERAS) protocols in thoracic surgery have been demonstrated to impact length of stay (LOS), complication rates, and postoperative opioid use. However, ERAS protocols for minimally invasive lung resections have not been well described. Given most lung resections are now performed minimally invasively, there is a gap in the literature regarding the efficacy of ERAS protocols in this setting. In this study, we analyzed patient outcomes following implementation of an ERAS protocol for minimally invasive lung resections., Methods: Outcome data was retrospectively collected for 442 patients undergoing minimally invasive lung resections between January 1 st , 2015 and October 26 th , 2021. Patients were divided into either a pre-ERAS (n=193) or ERAS (n=249) group. Primary outcomes included LOS, postoperative complications, intensive care unit (ICU) admission status, 30-day hospital readmissions, and 30-day mortality. Secondary outcomes included common postoperative complications required for the Society for Thoracic Surgeons (STS) database., Results: We observed an overall decrease in median LOS (4.0 vs. 3.0 days, P=0.030) and ICU admission status (15% vs. 7.6%, P=0.020) after implementation of our ERAS protocol. The difference in LOS was significantly lower for anatomic lung resections, but not non-anatomic resections. There was no difference in 30-day readmissions and a 0% mortality rate in both groups. Overall, there was a low complication rate that was similar between groups., Conclusions: The implementation of an ERAS protocol led to decreased LOS and decreased ICU admission in patients undergoing minimally invasive lung resection. Process standardization optimizes performance by providers by decreasing decision fatigue and improving decision making, which may contribute to the improved outcomes observed in this study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1500/coif). M.W.M. received lecture fees from Intuitive Surgical, unrelated to the content of this manuscript. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Vascularized composite allotransplantation (VCA) has become a valid therapeutic option to restore form and function after devastating tissue loss. However, the need for high-dose multidrug immunosuppression to maintain allograft survival is still hampering more widespread application of VCA. In this study, we investigated the immunoregulatory potential of costimulation blockade (CoB; CTLA4-Ig and anti-CD154 mAb) combined with nonmyeoablative total body irradiation (TBI) to promote allograft survival of VCA in a fully MHC-mismatched mouse model of orthotopic hind limb transplantation. Compared with untreated controls (median survival time [MST] 8 days) and CTLA4-Ig treatment alone (MST 17 days), CoB treatment increased graft survival (MST 82 days), and the addition of nonmyeloablative TBI led to indefinite graft survival (MST > 210 days). Our analysis suggests that VCA-derived BM induced mixed chimerism in animals treated with CoB and TBI + CoB, promoting gradual deletion of alloreactive T cells as the underlying mechanism of long-term allograft survival. Acceptance of donor-matched secondary skin grafts, decreased ex vivo T cell responsiveness, and increased graft-infiltrating Tregs further indicated donor-specific tolerance induced by TBI + CoB. In summary, our data suggest that vascularized BM-containing VCAs are immunologically favorable grafts promoting chimerism induction and long-term allograft survival in the context of CoB.

In vivo animal model systems, and in particular mouse models, have evolved into powerful and versatile scientific tools indispensable to basic and translational research in the field of transplantation medicine. A vast array of reagents is available exclusively in this setting, including mono- and polyclonal antibodies for both diagnostic and interventional applications. In addition, a vast number of genotyped, inbred, transgenic, and knock out strains allow detailed investigation of the individual contributions of humoral and cellular components to the complex interplay of an immune response and make the mouse the gold standard for immunological research. Vascularized Composite Allotransplantation (VCA) delineates a novel field of transplantation using allografts to replace "like with like" in patients suffering traumatic or congenital tissue loss. This surgical methodological protocol shows the use of a non-suture cuff technique for super-microvascular anastomosis in an orthotopic mouse hind limb transplantation model. The model specifically allows for comparison between established paradigms in solid organ transplantation with a novel form of transplants consisting of various different tissue components. Uniquely, this model allows for the transplantation of a viable vascularized bone marrow compartment and niche that have the potential to exert a beneficial effect on the balance of immune acceptance and rejection. This technique provides a tool to investigate alloantigen recognition and allograft rejection and acceptance, as well as enables the pursuit of functional nerve regeneration studies to further advance this novel field of transplantation.

Exploration of novel strategies in organ transplantation to prolong allograft survival and minimizing the need for long-term maintenance immunosuppression must be pursued. Employing vascularized bone marrow transplantation and co-transplantation of the thymus have shown promise in this regard in various animal models. Vascularized bone marrow transplantation allows for the uninterrupted transfer of donor bone marrow cells within the preserved donor microenvironment, and the incorporation of thymus tissue with vascularized bone marrow transplantation has shown to increase T-cell chimerism ultimately playing a supportive role in the induction of immune regulation. The combination of solid organ and vascularized composite allotransplantation can uniquely combine these strategies in the form of a novel transplant model. Murine models serve as an excellent paradigm to explore the mechanisms of acute and chronic rejection, chimerism, and tolerance induction, thus providing the foundation to propagate superior allograft survival strategies for larger animal models and future clinical application. Herein, we developed a novel heterotopic en bloc chest wall, thymus, and heart transplant model in mice using a cervical non-suture cuff technique. The experience in syngeneic and allogeneic transplant settings is described for future broader immunological investigations via an instructional manuscript and video supplement.