modified-langendorff-perfusion-for-extended-perfusion-times-rodent

Modified Langendorff Perfusion for Extended Perfusion Times of Rodent Cardiac Grafts

Despite important advancements in the diagnosis and treatment of cardiovascular diseases (CVDs), the field is in urgent need of increased research and ...

cardiac-loading-using-passive-left-atrial-pressurization-passive

Cardiac Loading using Passive Left Atrial Pressurization and Passive Afterload for Graft Assessment

Ex vivo machine perfusion or normothermic machine perfusion is a preservation method that has gained great importance in the transplantation field. ...

Massachusetts General Hospital

Massachusetts General Hospital, Harvard Medical School

Although immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 (PD-1), can deliver durable antitumor effects, most patients with cancer fail to respond. Recent studies suggest that ICI efficacy correlates with a higher load of tumor-specific neoantigens and development of vitiligo in patients with melanoma. Here, we report that patients with low melanoma neoantigen burdens who responded to ICI had tumors with higher expression of pigmentation-related genes. Moreover, expansion of peripheral blood CD8 T cell populations specific for melanocyte antigens was observed only in patients who responded to anti-PD-1 therapy, suggesting that ICI can promote breakdown of tolerance toward tumor-lineage self-antigens. In a mouse model of poorly immunogenic melanomas, spreading of epitope recognition toward wild-type melanocyte antigens was associated with markedly improved anti-PD-1 efficacy in two independent approaches: introduction of neoantigens by ultraviolet (UV) B radiation mutagenesis or the therapeutic combination of ablative fractional photothermolysis plus imiquimod. Complete responses against UV mutation-bearing tumors after anti-PD-1 resulted in protection from subsequent engraftment of melanomas lacking any shared neoantigens, as well as pancreatic adenocarcinomas forcibly overexpressing melanocyte-lineage antigens. Our data demonstrate that somatic mutations are sufficient to provoke strong antitumor responses after checkpoint blockade, but long-term responses are not restricted to these putative neoantigens. Epitope spreading toward T cell recognition of wild-type tumor-lineage self-antigens represents a common pathway for successful response to ICI, which can be evoked in neoantigen-deficient tumors by combination therapy with ablative fractional photothermolysis and imiquimod.

Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses.

Pregnant and lactating women were excluded from initial coronavirus disease 2019 vaccine trials; thus, data to guide vaccine decision making are lacking.

Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study.

The clinical significance of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) RNA in stool remains uncertain. We found that extrapulmonary dissemination of infection to the gastrointestinal tract, assessed by the presence of SARS-CoV-2 RNA in stool, is associated with decreased coronavirus disease 2019 (COVID-19) survival. Measurement of SARS-CoV-2 RNA in stool may have utility for clinical risk assessment.

Fecal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) RNA Is Associated With Decreased Coronavirus Disease 2019 (COVID-19) Survival.

Commentary: Crossing the Rubicon-pre-emptive recipient bilateral pneumonectomy and delayed lung transplantation.

Donor organ demand continues to outpace supply in heart transplantation. Utilization of donation after circulatory death (DCD) hearts could significantly increase heart donor availability for patients with advanced heart failure.

Hemodynamic and Clinical Performance of Hearts Donated After Circulatory Death.

Donation after circulatory death (DCD) donor hearts recovered using the direct procurement and perfusion method experience variable durations of warm ischemia at the time of procurement (WIP). We used the Organ Procurement and Transplantation Network database to assess the effect of WIP on 30-day mortality after DCD heart transplantation. The analysis evaluated outcomes in 237 recipients of DCD heart transplantation, demonstrating an optimal WIP cut point of <36 minutes. Multivariable logistic regression modeling identified donor left ventricular ejection fraction (LVEF) <60% as an independent predictor of 30-day mortality. The area under the receiver operating characteristic curve for predicting 30-day mortality based on WIP ≥36 minutes and donor LVEF <60% was 0.90. Based on these findings, we do not recommend proceeding with DCD heart transplantation for patients with WIP ≥36 minutes, particularly in donors with LVEF <60%.

The effect of warm ischemia and donor ejection fraction on 30-day mortality after donation after circulatory death heart transplantation: A national database analysis.

Since the beginning of the pandemic, coronavirus disease 2019 (COVID-19) has caused debilitating lung failure in many patients. Practitioners have understandably been hesitant to use lungs from donors with COVID-19 for transplantation. This study aimed to analyze the characteristics and short-term outcomes of lung transplantation from donors with recent positive COVID-19 testing results.

Is Transplantation With Coronavirus Disease 2019-Positive Donor Lungs Safe? A US Nationwide Analysis.

Static ice storage has long been the standard-of-care for lung preservation, although freezing injury limits ischemic time (IT). Controlled hypothermic storage (CHS) at elevated temperature could safely extend IT. This retrospective analysis assesses feasibility and safety of CHS with IT > 15 hours. Three lung transplant (LuTx) centers (April-October 2023) included demographics, storage details, IT, and short-term outcome from 13 LuTx recipients (8 male, 59 years old). Donor lungs were preserved in a portable CHS device at 7 (5-9.3)°C. Indication was overnight bridging and/or long-distance transport. IT of second-implanted lung was 17.3 (15.1-22) hours. LuTx were successful, 4/13 exhibited primary graft dysfunction grade 3 within 72 hours and 0/13 at 72 hours. Post-LuTx mechanical ventilation was 29 (7-442) hours. Intensive care unit stay was 9 (5-28) and hospital stay 30 (16-90) days. Four patients needed postoperative extracorporeal membrane oxygenation (ECMO). One patient died (day 7) following malpositioning of an ECMO cannula. This multicenter experience demonstrates the possibility of safely extending IT > 15 hours by CHS.

Extended ischemic time (>15 hours) using controlled hypothermic storage in lung transplantation: A multicenter experience.

The current understanding of the safety of heart transplantation from COVID-19+ donors is uncertain. Preliminary studies suggest that heart transplants from these donors may be feasible. We analyzed 1-year outcomes in COVID-19+ donor heart recipients using 1:3 propensity matching. The OPTN database was queried for adult heart transplant recipients between 1 January 2020 and 30 September 2022. COVID-19+ donors were defined as those who tested positive on NATs or antigen tests within 21 days prior to procurement. Multiorgan transplants, retransplants, donors without COVID-19 testing, and recipients allocated under the old heart allocation system were excluded. A total of 7211 heart transplant recipients met the inclusion criteria, including 316 COVID-19+ donor heart recipients. Further, 290 COVID-19+ donor heart recipients were matched to 870 COVID-19- donor heart recipients. Survival was similar between the groups at 30 days ( = 0.46), 6 months ( = 0.17), and 1 year ( = 0.07). Recipients from COVID-19+ donors in the matched cohort were less likely to experience postoperative acute rejection prior to discharge ( = 0.01). National COVID-19+ donor heart usage varied by region: region 11 transplanted the most COVID-19+ hearts (15.8%), and region 6 transplanted the fewest (3.2%). Our findings indicate that COVID-19+ heart transplantation can be performed with safe early outcomes. Further analyses are needed to determine if long-term outcomes are equivalent between groups.

ArticleTotal : 2	Year
Publication title Cited by 2	2024
Publication title Cited by 7	2024

Article	Year
Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses. Science translational medicine\| PubMed ID: 33597266	2021
Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study. American journal of obstetrics and gynecology\| PubMed ID: 33775692	2021
Fecal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) RNA Is Associated With Decreased Coronavirus Disease 2019 (COVID-19) Survival. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America\| PubMed ID: 34245255	2022
Commentary: Crossing the Rubicon-pre-emptive recipient bilateral pneumonectomy and delayed lung transplantation. JTCVS techniques\| PubMed ID: 35224517	2022
Hemodynamic and Clinical Performance of Hearts Donated After Circulatory Death. Journal of the American College of Cardiology\| PubMed ID: 36175050	2022
The effect of warm ischemia and donor ejection fraction on 30-day mortality after donation after circulatory death heart transplantation: A national database analysis. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation\| PubMed ID: 37506954	2023
Is Transplantation With Coronavirus Disease 2019-Positive Donor Lungs Safe? A US Nationwide Analysis. The Annals of thoracic surgery\| PubMed ID: 37506993	2023
Extended ischemic time (>15 hours) using controlled hypothermic storage in lung transplantation: A multicenter experience. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation\| PubMed ID: 38360161	2024
One Year Outcomes Following Transplantation with COVID-19-Positive Donor Hearts: A National Database Cohort Study. Journal of cardiovascular development and disease\| PubMed ID: 38392260	2024
Pulsatile ECMO: The Future of Mechanical Circulatory Support for Severe Cardiogenic Shock. JACC. Basic to translational science\| PubMed ID: 38680959	2024

S. Alireza Rabi

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