The appropriate selection of lung transplant recipients is an important determinant of outcomes. This consensus document is an update of the recipient selection guidelines published in 2006. The ...Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) organized a Writing Committee of international experts to provide consensus opinion regarding the appropriate timing of referral and listing of candidates for lung transplantation. A comprehensive search of the medical literature was conducted with the assistance of a medical librarian. Writing Committee members were assigned specific topics to research and discuss. The Chairs of the Writing Committee were responsible for evaluating the completeness of the literature search, providing editorial support for the manuscript, and organizing group discussions regarding its content. The consensus document makes specific recommendations regarding the timing of referral and of listing for lung transplantation. These recommendations include discussions not present in previous ISHLT guidelines, including lung allocation scores, bridging to transplant with mechanical circulatory and ventilator support, and expanded indications for lung transplantation. In the absence of high-grade evidence to support decision making, these consensus guidelines remain part of a continuum of expert opinion based on available studies and personal experience. Some positions are immutable. Although transplant is rightly a treatment of last resort for end-stage lung disease, early referral allows proper evaluation and thorough patient education. Subsequent waiting list activation implies a tacit agreement that transplant offers a significant individual survival advantage. It is both the challenge and the responsibility of the transplant community globally to ensure organ allocation maximizes the potential benefits of a scarce resource, thereby achieving that advantage.
A decision to withdraw life-sustaining treatment (WLST) is derived by a conclusion that further treatment will not enable a patient to survive or will not produce a functional outcome with acceptable ...quality of life that the patient and the treating team regard as beneficial. Although many hospitalized patients die under such circumstances, controlled donation after the circulatory determination of death (cDCDD) programs have been developed only in a reduced number of countries. This International Collaborative Statement aims at expanding cDCDD in the world to help countries progress towards self-sufficiency in transplantation and offer more patients the opportunity of organ donation. The Statement addresses three fundamental aspects of the cDCDD pathway. First, it describes the process of determining a prognosis that justifies the WLST, a decision that should be prior to and independent of any consideration of organ donation and in which transplant professionals must not participate. Second, the Statement establishes the permanent cessation of circulation to the brain as the standard to determine death by circulatory criteria. Death may be declared after an elapsed observation period of 5 min without circulation to the brain, which confirms that the absence of circulation to the brain is permanent. Finally, the Statement highlights the value of perfusion repair for increasing the success of cDCDD organ transplantation. cDCDD protocols may utilize either in situ or ex situ perfusion consistent with the practice of each country. Methods to accomplish the in situ normothermic reperfusion of organs must preclude the restoration of brain perfusion to not invalidate the determination of death.
Little is known regarding appropriate patient selection for and clinical outcomes with lung transplantation for respiratory failure due to Covid-19. This study analyzes lung transplantations reported ...in the United Network for Organ Sharing registry from August 2020 through September 2021.
Objective The study objective was to compare the outcomes of intraoperative extracorporeal membrane oxygenation versus cardiopulmonary bypass support in lung transplantation. Methods We performed a ...retrospective cohort study from a prospective database of adult lung transplantations performed at the University of Toronto from 2007 to 2013. Among 673 lung transplantations performed in the study period, 267 (39.7%) required cardiopulmonary support. There were 39 cases of extracorporeal membrane oxygenation (2012-2013) and 228 cases of cardiopulmonary bypass (2007-2013). Patients who were bridged with extracorporeal life support, underwent a concomitant cardiac procedure, received a combined liver or heart transplant, were colonized with Burkholderia cenocepacia , or required emergency cannulation for cardiopulmonary support were excluded. Finally, 33 extracorporeal membrane oxygenation cases were matched with 66 cases of cardiopulmonary bypass according to age (±10 years), lung transplantation indication, and procedure type (bilateral vs single lung transplantation). Results Recipient factors such as body mass index and gender were not different between extracorporeal membrane oxygenation and cardiopulmonary bypass groups. Furthermore, donor variables were similar, including age, body mass index, last PaO2/FiO2 ratio, smoking history, positive airway cultures, and donor type (brain death and donation after cardiac death). Early outcomes, such as mechanical ventilation requirement, length of intensive care unit stay, and length of hospital stay, significantly favored extracorporeal membrane oxygenation (median 3 vs 7.5 days, P = .005; 5 vs 9.5 days, P = .026; 19 vs 27 days, P = .029, respectively). Perioperative blood product transfusion requirement was lower in the extracorporeal membrane oxygenation group. The 90-day mortality for the extracorporeal membrane oxygenation group was 6% versus 15% for cardiopulmonary bypass ( P = .32). Conclusions Extracorporeal membrane oxygenation may be considered as the first choice of intraoperative cardiorespiratory support for lung transplantation.
Many drugs have been approved for clinical trials for the treatment of COVID-19 disease, focusing on either antiviral or anti-inflammatory approaches. Combining antiviral and anti-inflammatory drugs ...or therapies together may be more effective. Human alpha-1 antitrypsin (A1AT) is a blood circulating glycoprotein that is best known as a protease inhibitor. It has been used to treat emphysema patients with A1AT deficiency for decades. We and others have demonstrated its role in reducing acute lung injury by inhibiting inflammation, cell death, coagulation, and neutrophil elastase activation. Recently, A1AT has been found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by inhibiting transmembrane serine protease 2 (TMPRSS2), a protease involved in the entry of SARS-CoV-2 into host cells. This dual role of both antiviral infection and anti-inflammation makes A1AT a unique and excellent candidate for COVID-19 treatment. Three clinical trials of A1AT for COVID-19 treatment have recently been approved in several countries. It is important to determine whether A1AT can prevent the progress from moderate to severe lung injury and eventually to be used to treat COVID-19 patients with acute respiratory distress syndrome.
Objective Lung cancer is the leading cause of cancer death in North America. Low-dose computed tomography screening can reduce lung cancer–specific mortality by 20%. Method The American Association ...for Thoracic Surgery created a multispecialty task force to create screening guidelines for groups at high risk of developing lung cancer and survivors of previous lung cancer. Results The American Association for Thoracic Surgery guidelines call for annual lung cancer screening with low-dose computed tomography screening for North Americans from age 55 to 79 years with a 30 pack-year history of smoking. Long-term lung cancer survivors should have annual low-dose computed tomography to detect second primary lung cancer until the age of 79 years. Annual low-dose computed tomography lung cancer screening should be offered starting at age 50 years with a 20 pack-year history if there is an additional cumulative risk of developing lung cancer of 5% or greater over the following 5 years. Lung cancer screening requires participation by a subspecialty-qualified team. The American Association for Thoracic Surgery will continue engagement with other specialty societies to refine future screening guidelines. Conclusions The American Association for Thoracic Surgery provides specific guidelines for lung cancer screening in North America.
Availability of organs is a limiting factor for lung transplantation, leading to substantial mortality rates on the wait list. Use of organs from donors with transmissible viral infections, such as ...hepatitis C virus (HCV), would increase organ donation, but these organs are generally not offered for transplantation due to a high risk of transmission. Here, we develop a method for treatment of HCV-infected human donor lungs that prevents HCV transmission. Physical viral clearance in combination with germicidal light-based therapies during normothermic ex-vivo Lung Perfusion (EVLP), a method for assessment and treatment of injured donor lungs, inactivates HCV virus in a short period of time. Such treatment is shown to be safe using a large animal EVLP-to-lung transplantation model. This strategy of treating viral infection in a donor organ during preservation could significantly increase the availability of organs for transplantation and encourages further clinical development.
Abstract Objective To evaluate a new protocol of accelerated hemithoracic intensity-modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP) for patients with resectable ...malignant pleural mesothelioma (MPM). Methods A total of 25 Gy of radiation was delivered in 5 daily fractions over 1 week to the entire ipsilateral hemithorax with concomitant boost of 5 Gy to volumes at high risk based on computed tomography and positron emission tomography scan findings. EPP was performed at 6 ± 2 days after the end of radiation therapy. Adjuvant chemotherapy was offered to patients with ypN2 disease. Results A total of 62 patients were included between November 2008 and October 2014. One patient died in the hospital 2 months after EPP, for an operative mortality of 1.6%, and 2 died after discharged from the hospital for an overall treatment-related mortality (grade 5 toxicity) of 4.8%. Twenty-four patients (39%) developed grade 3 to 5 (grade 3+) complications. On final pathology, 94% of the patients were stage III or IV, and 52% had ypN2 disease. The median survival for all patients as an intention-to-treat analysis was 36 months. The median overall survival and disease-free survival was 51 and 47 months, respectively, in epithelial subtypes, compared with 10 and 8 months in biphasic subtypes ( P = .001). Ipsilateral chest recurrence occurred in 8 patients. Conclusions Accelerated hemithoracic IMRT followed by EPP has become our preferred approach for resectable MPM. The results have been encouraging in patients with epithelial subtype.
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