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Ischemia-reperfusion injury is an inevitable event during organ transplantation and represents a primary risk factor for the development of early graft dysfunction in lung, heart, liver, and kidney transplant recipients. Recent studies have implicated recipient neutrophils as key mediators of this process and also have found that early innate immune responses after transplantation can ultimately augment adaptive alloimmunity and affect late graft outcomes. Here, we discuss signaling pathways involved in neutrophil recruitment and activation after ischemia-mediated graft injury in solid organ transplantation with an emphasis on lung allografts, which have been the focus of recent studies. These findings suggest novel therapeutic interventions that target ischemia-reperfusion injury-mediated graft dysfunction in transplant recipients.

The rising need for lung transplantation over recent years has not paralleled the availability of suitable lung allografts. The number of lung transplantations performed each year in the United States remains limited by an inadequate supply of suitable donors as well as low donor utilization rates. While several methods have been proposed for increasing the donor pool, there is considerable disparity between acceptance and utilization of these practices among transplant centers. In this review article, we explore various approaches for enhancing donor selection and expanding the donor pool. We discuss the use of “extended criteria” donors including high risk groups such as drug overdose donors, and we examine the role of techniques in donor assessment and selection such as the use of computed tomography for accurate size matching. We review topics in donor management such as the establishment of specialized donor care facilities and the implementation of lung-focused resuscitation protocols, and we discuss advancements in donor procurement such as the utilization of local procurement teams. We also review barriers to donation, such as variability in organ procurement organization (OPO) consent practices, as well as patient-specific factors such as religious or cultural beliefs. Addressing these aspects of donor evaluation, management, and accessibility is essential in maximizing the number of lungs available for transplantation within the existing donor pool.

The new lung allocation policy has led to an increase in distant donors and consequently enhanced logistical burden of procuring organs. Though early single-center studies noted similar outcomes between same-team transplantation (ST, procuring team from transplanting center) and different-team transplantation (DT, procuring team from different center), the efficacy of DT in the contemporary era remains unclear. In this study, we evaluated the trend of DT, rate of transplanting both donor lungs, 1-year graft survival, and risk of Grade 3 primary graft dysfunction (PGD) using the Scientific Registry of Transplant Recipient (SRTR) database from 2006 to 2018. A total of 21619 patients (DT 2085, 9.7%) with 19837 donors were included. Utilization of DT decreased from 15.9% in 2006 to 8.5% in 2018. Proportion of two-lung donors was similar between the groups, and DT had similar 1-year graft survival as ST for both double (DT, HR 1.108, 95% CI 0.894 – 1.374) and single lung transplants (DT, HR 1.094, 95% CI 0.931 – 1.286). Risk of Grade 3 PGD was also similar between ST and DT. Given our results, expanding DT may be a feasible option for improving lung procurement efficiency in the current era, particularly in light of the COVID-19 pandemic.

Innate immune pathways early after pulmonary transplantation have been shown to cause primary graft dysfunction (PGD) and also predispose to late graft failure. Recent studies in animal models have elucidated critical mechanisms governing such innate immune responses. Here, we discuss pathways of inflammatory cell death, triggers for sterile and infectious inflammation, and signaling cascades that mediate lung injury early after transplantation. These studies highlight potential avenues for lung-specific therapies early following lung transplantation to dampen innate immune responses and improve outcomes.

Purpose of review Immune responses following lung transplantation continue to result in high rates of allograft failure and rejection, and current immunosuppression does not address the unique immunologic properties of the lung. Here, we review recent studies on lung allograft tolerance and alloimmunity and discuss implications for immunosuppression. Recent findings Processes governing tolerance and alloimmunity in lung allografts differ from other solid organs. Recent studies have suggested that allorecognition is regulated at the level of the lung graft. Furthermore, certain cell populations essential for lung allograft tolerance may facilitate rejection in other organs. Induction of lung allograft tolerance is associated with the formation of tertiary lymphoid organs, which are enriched in regulatory T cells and play an important role in preventing rejection. Summary Recent discoveries regarding alloactivation and the regulation of tolerance following lung transplantation have introduced exciting potential avenues for the development of lung-specific immunosuppression.

Murine models of cardiac transplantation are frequently utilized to study ischemia-reperfusion injury, innate and adaptive immune responses after transplantation, and the impact of immunomodulatory therapies on graft rejection. Heterotopic cervical heart transplantation in mice was first described in 1991 using sutured anastomoses and subsequently modified to include cuff techniques. This modification allowed for improved success rates, and since then, there have been multiple reports that have proposed further technical improvements. However, translation into more widespread utilization remains limited due to the technical difficulty associated with graft anastomoses, which requires precision to achieve adequate length and caliber of the cuffs to avoid vascular anastomotic twisting or excessive tension, which can result in damage to the graft. The present protocol describes a modified technique for performing heterotopic cervical cardiac transplantation in mice which involves cuff placement on the recipient's common carotid artery and the donor's pulmonary artery in alignment with the direction of the blood flow.

Background Pancreatic cancer has been shown to cause diabetes mellitus, and diabetes mellitus has been shown to be a risk factor for pancreatic cancer. The effect of pancreaticoduodenectomy on risk for development of diabetes mellitus is unclear. This study used hemoglobin A1c to determine the incidence of diabetes mellitus development following pancreaticoduodenectomy based on preoperative risk of diabetes mellitus. Methods Retrospective review of patients undergoing pancreaticoduodenectomy was performed with comparison of preoperative diabetes mellitus status and hemoglobin A1c with development of diabetes mellitus postoperatively. Risk ratios were calculated to determine the risk for diabetes mellitus development. Results Among 90 patients who met inclusion criteria, 26.7% developed new-onset or worsening diabetes mellitus following pancreaticoduodenectomy. Of those with hemoglobin A1c ≤ 5.6%, only 7.7% of patients developed diabetes mellitus. Patients at risk for diabetes mellitus preoperatively had 4.0 times greater risk for development of diabetes mellitus following pancreaticoduodenectomy. Conclusion Hemoglobin A1c levels should be used to identify patients at risk for new-onset or worsening diabetes mellitus following pancreaticoduodenectomy., Highlights • Preoperative hemoglobin A1c (HbA1c) is a useful marker for predicting development of new-onset or worsening diabetes mellitus (DM) following pancreaticoduodenectomy (PD). • Patients with HbA1c ≤ 5.6% are very unlikely to develop DM following PD. • Patients at risk for DM (HbA1c 5.7%–6.4%) have a 4-fold greater risk for developing DM following PD than patients with HbA1c ≤ 5.6%. • For patients who develop DM following PD, median time to diagnosis is 12 months.

Scarce data is available on therapeutic anticoagulation (AC) in patients undergoing pulmonary transplantation. We describe our institutional experience with AC-induced coagulopathy in recipients at the time of transplantation and evaluate its impact on posttransplant outcomes.Records of adult patients on therapeutic AC at the time of lung transplantation from January 2014 to July 2021 were reviewed. Administration of preoperative pharmacologic reversal was assessed, with adequate reversal defined as international normalized ratio (INR) ≤1.5. We evaluated the incidence of major bleeding complications [delayed sternal closure, reoperation due to bleeding, chest tube output ≥1,500 cc, ≥4 units of packed red blood cells, ≥4 units of platelets, or ≥5 units of fresh frozen plasma (FFP)], major thrombotic complications [venous thromboembolism (VTE) or other major thrombosis on imaging], and inpatient mortality.Of 602 lung transplant recipients, 10 patients taking preoperative warfarin were included in the study. While most patients received pharmacologic reversal preoperatively (n=9, 90%), successful reversal was rarely achieved (n=3, 30%). Inadequate INR reversal was associated with major bleeding events (n=6, 60%). Major thrombotic complications were more frequent (n=7, 70%) than bleeding events. Notably, all fatalities within the cohort (n=2, 20%) were associated with thrombotic, but not bleeding, complications.This is the first known report on the incidence and impact of AC-induced coagulopathy in patients undergoing lung transplantation. Major thrombotic events are frequent and associated with high mortality. Routine surveillance and treatment may be warranted.

Acute interstitial pneumonia (AIP), also known as Hamman-Rich syndrome, is a rare and rapidly progressive idiopathic interstitial lung disease with a high mortality rate. Treatment is limited to supportive care and empirical high-dose steroids; however, outcomes are generally poor. There are few reports of lung transplantation (LTx) in patients with AIP.We retrospectively identified patients with AIP among those who underwent LTx at our center between January 2008 and December 2020.During the study period, 4 patients with AIP underwent bilateral LTx: 3 men and 1 woman, between 30 and 57 years of age. The lung allocation score ranged between 71 and 89. Of the 4 patients, 2 needed extracorporeal membrane oxygenation and mechanical ventilation (MV) and 1 needed MV preoperatively. Time of onset to transplant ranged from 1 to 3 months. None of the patients had primary graft dysfunction after LTx; 2 had acute cellular rejection and 1 had chronic lung allograft dysfunction. The 4 patients are alive with survival ranging between 1 and 12 years after LTx.AIP should be considered in patients with acute respiratory failure without a clear etiology. Our study showed that LTx led to good outcomes and should be considered as a treatment option in appropriate candidates.

Tertiary lymphoid organs (TLOs) are collections of immune cells resembling secondary lymphoid organs (SLOs) that form in peripheral, non-lymphoid tissues in response to local chronic inflammation. While their formation mimics embryologic lymphoid organogenesis, TLOs form after birth at ectopic sites in response to local inflammation resulting in their ability to mount diverse immune responses. The structure of TLOs can vary from clusters of B and T lymphocytes to highly organized structures with B and T lymphocyte compartments, germinal centers, and lymphatic vessels (LVs) and high endothelial venules (HEVs), allowing them to generate robust immune responses at sites of tissue injury. Although our understanding of the formation and function of these structures has improved greatly over the last 30 years, their role as mediators of protective or pathologic immune responses in certain chronic inflammatory diseases remains enigmatic and may differ based on the local tissue microenvironment in which they form. In this review, we highlight the role of TLOs in the regulation of immune responses in chronic infection, chronic inflammatory and autoimmune diseases, cancer, and solid organ transplantation.

Bronchial arteriovenous malformations (AVMs) are usually asymptomatic findings noted on imaging but may present with massive hemoptysis following endobronchial rupture. Initial treatment usually involves transcatheter embolization with surgery reserved for refractory cases. Here, we present a patient with large-volume hemoptysis following bronchial AVM rupture. Attempted endovascular management was unsuccessful due to unfavorable anatomy and hemodynamic instability, necessitating emergent use of extracorporeal membrane oxygenation (ECMO) followed by right bilobectomy.

Background Donor hearts and lungs are more susceptible to the inflammatory physiologic changes that occur after brain death. Prior investigations have shown that protocolized management of potential organ donors can rehabilitate donor organs that are initially deemed unacceptable. In this review we discuss advances in donor management models with particular attention to the specialized donor care facility model. In addition we review specific strategies to optimize donor thoracic organs and improve organ yield in thoracic transplantation. Methods We performed a literature review by searching the PubMed database for medical subject heading terms associated with organ donor management models. We also communicated with our local organ procurement organization to gather published and unpublished information first-hand. Results The specialized donor care facility model has been shown to improve the efficiency of organ donor management and procurement while reducing costs and minimizing travel and its associated risks. Lung protective ventilation, recruitment of atelectatic lung, and hormone therapy (eg, glucocorticoids and triiodothyronine/thyroxine) are associated with improved lung utilization rates. Stroke volume–based resuscitation is associated with improved heart utilization rates, whereas studies evaluating hormone therapy (eg, glucocorticoids and triiodothyronine/thyroxine) have shown variable results. Conclusions Lack of high-quality prospective evidence results in conflicting practices across organ procurement organizations, and best practices remain controversial. Future studies should focus on prospective, randomized investigations to evaluate donor management strategies. The specialized donor care facility model fosters a collaborative environment that encourages academic inquiry and is an ideal setting for these investigations.

Objectives To investigate clinicopathologic and treatment factors associated with survival in adult head and neck sarcomas in the National Cancer Database (NCDB). To analyze whether treatment settings and therapies received influence survival outcomes and to compare trends in utilization via an aggregated national data set. Study Design Prospectively gathered data. Setting NCDB. Subjects and Methods The study comprised a total of 6944 adult patients treated for a head and neck sarcoma from January 2004 to December 2013. Overall survival (OS) was the primary outcome. Results Increased age and tumor size, nodal involvement, and poorly differentiated histology had significantly reduced OS ( P < .001). Angiosarcoma, malignant nerve sheath tumor, malignant fibrous histiocytoma, osteosarcoma, and rhabdomyosarcoma histologic subtypes had significantly reduced OS, while liposarcoma, chondrosarcoma, and chordoma had improved OS ( P < .001). Utilization of surgical therapy was associated with improved OS, while positive surgical margins were associated with treatment at a community-based cancer program and had reduced OS ( P < .001). On multivariate analysis, treatment with radiation and/or chemotherapy was not significantly associated with OS; however, primary treatment with definitive chemoradiotherapy had significantly reduced OS. Patients treated at academic/research cancer programs (n = 3874) had significantly improved 5- and 10-year OS (65% and 54%, respectively) when compared with patients treated at community-based cancer programs (n = 3027; 49% and 29%; P < .001). The percentage utilization of these programs (56% vs 44%) did not change over the study period. Conclusion For adult head and neck sarcomas, treatment at an academic/research cancer program was associated with improved survival; however, despite increasing medical specialization, the percentage utilization of these programs for this rare tumor remains constant.

Importance Patients with head and neck squamous cell cancer (HNSCC) are often uninsured or underinsured at the time of their diagnosis. This access to care has been shown to influence treatment decisions and survival outcomes. Objective To examine the association of the Patient Protection and Affordable Care Act (ACA) health care legislation with rates of insurance coverage and access to care among patients with HNSCC. Design, Setting, and Participants Prospectively gathered data from the Surveillance, Epidemiology, and End Results (SEER) database were used to examine rates of insurance coverage and access to care among 89 038 patients with newly diagnosed HNSCC from January 2007 to December 2014. Rates of insurance were compared between states that elected to expand Medicaid coverage in 2014 and states that opted out of the expansion. Statistical analysis was performed from January 1, 2007, to December 31, 2014. Main Outcomes and Measures Rates of insurance coverage and disease-specific and overall survival. Results Among 89 038 patients newly diagnosed with HNSCC (29 384 women and 59 654 men; mean [SD] age, 59.8 [7.6] years), there was an increase after implementation of the ACA in the percentage of patients enrolled in Medicaid (16.2% after vs 14.8% before; difference, 1.4%; 95% CI, 1.1%-1.7%) and private insurance (80.7% after vs 78.9% before; difference, 1.8%; 95% CI, 1.2%-2.4%). In addition, there was a large decrease in the rate of uninsured patients after implementation of the ACA (3.0% after vs 6.2% before; difference, 3.2%; 95% CI, 2.9%-3.5%). This decrease in the rate of uninsured patients and the associated increases in Medicaid and private insurance coverage were only different in the states that adopted the Medicaid expansion in 2014. No survival data are available after implementation of the ACA, but prior to that point, from 2007 to 2013, uninsured patients had reduced 5-year overall survival (48.5% vs 62.5%; difference, 14.0%; 95% CI, 12.8%-15.2%) and 5-year disease-specific survival compared with insured patients (56.6% vs 72.2%; difference, 15.6%; 95% CI, 14.0%-17.2%). Conclusions and Relevance Access to health care for patients with HNSCC was improved after implementation of the ACA, with an increase in rates of both Medicaid and private insurance and a 2-fold decrease in the rate of uninsured patients. These outcomes were demonstrated only in states that adopted the Medicaid expansion in 2014. Uninsured patients had poorer survival outcomes.

Evaluate current practice patterns in the use of adjuvant radiation for T1-2N1 OCSCC patients and investigate its efficacy in the population-based setting.This study extracted patients who were treated surgically for T1N1 and T2N1 OCSCC without adverse nodal features from the SEER database from 2004 to 2013. Patients with distant metastatic disease, unknown surgery or radiation status, or prior malignancies were excluded. Patients were divided into those who underwent surgical resection with and without adjuvant radiation. Disease-specific survival (DSS) and overall survival (OS) were the primary outcomes measured.746 patients met inclusion criteria and 70% received adjuvant radiation therapy. Treatment with adjuvant radiation therapy was significantly associated with improved 5-year DSS (65% versus 51%; p 0.001) and OS (54% versus 44%; p = 0.007) for T1N1 tumors. Likewise, improved 5-year DSS (58% versus 38%; p = 0.009) and OS (48% versus 28%; p = 0.004) was shown in T2N1 tumors. Patients with T2N1 tumors wer significantly more likely to receive adjuvant radiation (75% versus 63%; p 0.001). Those with insurance and high risk primary subsites: buccal, retromolar trigone, and hard palate were more likely to receive adjuvant radiation. The percent utilization of adjuvant radiation remained constant through the study period for T2N1 tumors (72-74%) but significantly decreased for T1N1 (71-55%) (p = 0.047).Adjuvant radiation therapy is independently associated with a significant survival benefit for patients with both T1N1 and T2N1 OCSCC. However, this study demonstrates that patients with T1N1 cancer are less likely to receive adjuvant radiation and utilization is decreasing.