Enhanced recovery after surgery pathway leads to decreased length of stay for patients undergoing minimally invasive lung resection.

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 1st, 2015 and October 26th, 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.

Vascularized composite allotransplantation combined with costimulation blockade induces mixed chimerism and reveals intrinsic tolerogenic potential.

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.

Mechanical Circulatory Support for Cardiogenic Shock in the Critically Ill.

Patients requiring mechanical circulatory support (MCS) constitute a heterogeneous group whose needs have guided the development of a broad range of MCS devices. Appropriate patient and device selection are important for maximizing the potential benefit of these therapies. Currently available devices can be deployed percutaneously or surgically implanted. They can also be configured for left, right, or biventricular support and remain in place for hours to years, offering varying levels of flow. In the critical care setting, patients with the highest acuity have the worst outcomes when receiving an implantable long-term ventricular assist device (VAD); therefore, shorter-term devices should be considered for stabilization and optimization prior to implantation of a long-term device. In this focused review for the critical care clinician, we discuss important considerations for identifying VAD candidates, identifying the range of devices available to support them, bridging strategies that may improve outcomes for patients who are critically ill, and identifying areas of ongoing research.

Split Tolerance in a Murine Model of Heterotopic En Bloc Chest Wall Transplantation.

BACKGROUND: Congenital and acquired chest wall deformities represent a significant challenge to functional reconstruction and may impact feasibility of heart transplantation for patients with end-stage organ failure. In the recent past, the concept of replacing like-with-like tissue by using vascularized composite allografts (VCA) has been enthusiastically employed for reconstruction of complex tissue defects. METHODS: In this study, we introduce a novel murine model for en bloc chest wall, heart, and thymus transplantation and thereby the use of complex tissue allografts for reconstruction of both chest wall defects and also end-stage organ failure. Additionally, this model allows us to study the features of combined vascularized bone marrow (VBM), thymus, and heart transplantation on allograft survival and function. Heterotopic chest wall, thymus, and heart transplants were performed in untreated syngeneic and allogeneic combinations and in allogeneic combinations treated with costimulation blockade (CTLA4-Ig and MR-1). RESULTS: Indefinite (ie, 150 d, N = 3) graft survival was observed in syngeneic controls. In untreated recipients of allogeneic grafts, the skin component was rejected after 10 (±1) days, whereas rejection of the heart occurred after 13 (± 1) days (N = 3). Costimulation blockade treatment prolonged survival of the heart and chest wall component (130 d, N = 3) as well as the VBM niche as evidenced by donor-specific chimerism (average: 2.35 ± 1.44%), whereas interestingly, the skin component was rejected after 13 (±1) days. CONCLUSION: Thus, this novel microsurgical model of VCA combined with solid organ transplantation is technically feasible and results in split tolerance when treated with costimulatory blockade.

Orthotopic Hind Limb Transplantation in the Mouse.

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.

A Novel Microsurgical Model for Heterotopic, En Bloc Chest Wall, Thymus, and Heart Transplantation in Mice.

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.