Liver transplant (LT) candidates today are older, have greater medical severity of illness, and have more cardiovascular comorbidities than ever before. In addition, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Cirrhotic cardiomyopathy, a condition characterized by increased cardiac output and a reduced ventricular response to stress, is present in up to 30% of patients with cirrhosis, thus challenging perioperative management. Current noninvasive tests that assess for subclinical coronary and myocardial disease have low sensitivity, and altered hemodynamics during the LT surgery can unmask latent cardiovascular disease either intraoperatively or in the immediate postoperative period. Therefore, this review, assembled by a group of multidisciplinary experts in the field and endorsed by the American Society of Transplantation Liver and Intestine and Thoracic and Critical Care Communities of Practice, provides a critical assessment of the diagnosis of cardiac and pulmonary vascular disease and interventions aimed at managing these conditions in LT candidates. Key points and practice-based recommendations for the diagnosis and management of cardiac and pulmonary vascular disease in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.
Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage‐specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer‐specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.
Patients undergoing evaluation for solid organ transplantation (SOT) frequently have a history of malignancy. Only patients with treated cancer are considered for SOT but the benefits of transplantation need to be balanced against the risk of tumor recurrence, taking into consideration the potential effects of immunosuppression. Prior guidelines on timing to transplant in patients with a prior treated malignancy do not account for current staging, disease biology, or advances in cancer treatments. To update these recommendations, the American Society of Transplantation (AST) facilitated a consensus workshop to comprehensively review contemporary literature regarding cancer therapies, cancer stage specific prognosis, the kinetics of cancer recurrence, as well as the limited data on the effects of immunosuppression on cancer‐specific outcomes. This document contains prognosis, treatment, and transplant recommendations for melanoma and hematological malignancies. Given the limited data regarding the risk of cancer recurrence in transplant recipients, the goal of the AST‐sponsored conference and the consensus documents produced are to provide expert opinion recommendations that help in the evaluation of patients with a history of a pretransplant malignancy for transplant candidacy.
IMPORTANCE Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis. OBJECTIVE To assess the effect of antimicrobial therapy on clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years were randomized from August 2017 to June 2019 (final follow-up was January 2020).INTERVENTIONS Patients were randomized in a 1:1 allocation ratio to receive antimicrobials (n = 254) or usual care alone (n = 259). Antimicrobials included co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily plus folic acid 5 mg daily, n = 128) or doxycycline (100 mg once daily if body weight <50 kg or 100 mg twice daily if Ն50 kg, n = 126). No placebo was administered in the usual care alone group. MAIN OUTCOMES AND MEASURESThe primary end point was time to first nonelective respiratory hospitalization or all-cause mortality. RESULTS Among the 513 patients who were randomized (mean age, 71 years; 23.6% women), all (100%) were included in the analysis. The study was terminated for futility on December 18, 2019. After a mean follow-up time of 13.1 months (median, 12.7 months), a total of 108 primary end point events occurred: 52 events (20.4 events per 100 patient-years [95% CI, 14.8-25.9]) in the usual care plus antimicrobial therapy group and 56 events (18.4 events per 100 patient-years [95% CI, 13.2-23.6]) in the usual care group, with no significant difference between groups (adjusted HR, 1.04 [95% CI, 0.71-1.53; P = .83]. There was no statistically significant interaction between the effect of the prespecified antimicrobial agent (co-trimoxazole vs doxycycline) on the primary end point (adjusted HR, 1.15 [95% CI 0.68-1.95] in the co-trimoxazole group vs 0.82 [95% CI, 0.46-1.47] in the doxycycline group; P = .66). Serious adverse events occurring at 5% or greater among those treated with usual care plus antimicrobials vs usual care alone included respiratory events (16.5% vs 10.0%) and infections (2.8% vs 6.6%); adverse events of special interest included diarrhea (10.2% vs 3.1%) and rash (6.7% vs 0%).CONCLUSIONS AND RELEVANCE Among adults with idiopathic pulmonary fibrosis, the addition of co-trimoxazole or doxycycline to usual care, compared with usual care alone, did not significantly improve time to nonelective respiratory hospitalization or death. These findings do not support treatment with these antibiotics for the underlying disease.
Intracardiac thrombus (ICT) is an intraoperative complication with high mortality that occurs during orthotopic liver transplantation (OLT). Patients with end‐stage liver disease have compromised coagulation pathways, and when combined with stressors of surgery, thrombi can form. However, it is unknown which patients are most likely to develop ICT. We performed a retrospective cohort study of all OLT patients at our hospital from 2010 to 2017 to identify risk factors for ICT. An analysis was performed with conventional bivariate tests and logistic regression. The incidence of ICT during OLT was 4.2% (22/528) with a 45.5% (10/22) mortality. Patients who developed ICT had higher physiologic Model for End‐Stage Liver Disease scores at the time of transplant (25.1 versus 32.4; P = 0.004), received grafts from donors with a higher body mass index (28.1 versus 32.2 kg/m2; P = 0.007), and had longer intraoperative warm ischemia times (53.1 versus 67.5 minutes; P = 0.001). The odds of developing ICT were significantly lower after administration of intravenous (IV) heparin prior to inferior vena cava (IVC) clamping compared with no administration of heparin (odds ratio, 0.25; 95% confidence interval, 0.08‐0.75; P = 0.01). In conclusion, the incidence of ICT at our institution is higher than previously reported, which may be explained by our routine use of transesophageal echocardiography. Although many factors associated with ICT in this study are nonmodifiable, administration of IV heparin prior to IVC cross‐clamping is modifiable and was found to be protective. Further studies will be needed to confirm findings and ultimately aid in preventing these lethal events.
Background. Portopulmonary hypertension is present in an estimated 5.3% to 8.5% of liver transplant candidates. Untreated, 5-year survival is estimated between 14% and 28%. Moderate-severe disease is a contraindication to liver transplant due to the high perioperative mortality, but patients optimized with pulmonary vasodilator therapy can become eligible for transplant. There is minimal data regarding posttransplant outcomes and ability to discontinue pulmonary vasodilator therapy posttransplant. Methods. We performed a single-center retrospective analysis to evaluate long-term outcomes of patients with moderate-severe portopulmonary hypertension who were optimized with pulmonary vasodilator therapy, became eligible for liver transplant, and subsequently underwent transplant. We identified 24 patients optimized with pulmonary vasodilator therapy who underwent subsequent liver transplantation and 25 patients who were treated with pulmonary vasodilator therapy alone. Results. In the transplanted cohort, 1-year survival from portopulmonary hypertension diagnosis date: 95.8%, 3-year survival: 90.9%, and 5-year survival: 90.9%. Posttransplant; 1-, 3-, and 5-year survival was 86.9%. Among transplanted patients, 41.6% (10/24) were optimized with nonparenteral therapy. Following transplantation, 100% (14/14) of the surviving patients were able to discontinue parenteral therapy; median time: 7.2 months (interquartile range: 5.1–8.9 mo), while 61.9% (13/21) were able to discontinue pulmonary vasodilator therapy altogether; median time: 13.9 months (interquartile range: 5.1–17.6 mo). Conclusions. Patients who are optimized with pulmonary vasodilator therapy before liver transplant can have excellent long-term outcomes posttransplant. Oral pulmonary vasodilator therapy can be effective treatment to qualify a patient for transplant, and the majority are able to wean from pulmonary vasodilator therapy entirely posttransplant.
Existing methods of academic publication provide limited opportunity to obtain stakeholder input on issues of broad interest. This article reports the results of an experiment to produce a collaborative, crowdsourced article examining a current controversial issue in transplant medicine (hereby referred to as the "C4 Article"). The editorial team as a whole selected the topic of organ allocation, then divided into six sections, each supported by an individual editorial team. Widely promoted by the American Journal of Transplantation, the C4 Article was open for public comment for 1 month. The nonblinded editorial teams reviewed the contributions daily and interacted with contributors in near-real time to clarify and expand on the content received. Draft summaries of each section were posted and subsequently revised as new contributions were received. One hundred ninety-four individuals viewed the manuscript, and 107 individuals contributed to the manuscript during the submission period. The article engaged the international transplant community in producing a contemporary delineation of issues of agreement and controversy related to organ allocation and identified opportunities for new policy development. This initial experience successfully demonstrated the potential of a crowdsourced academic manuscript to advance a broad-based understanding of a complex issue. K E Y W O R D S disparities, donors and donation, editorial/personal viewpoint, organ transplantation in general, waitlist management 1 | INTRODUC TI ON This manuscript is the result of an experiment to produce a collaborative, crowdsourced article examining a current and controversial issue in the field of transplantation. This C4 Article examines the issue of organ allocation. The perennial shortage of organs impacts all aspects of transplantation from basic research to health policy. Unlike other areas of medicine in which the need for care exceeds available resources, the scarcity of organs for transplantation cannot be rectified by a simple injection of funds. The rationing of available lifesaving organs is a reality of contemporary transplant medicine achieved through organ allocation rules. Principles of both utility and justice inform these rules. In the context of organ allocation, these principles are frequently in conflict. Periodic review of organ allocation policies ensures the optimal balance of the principles of justice and utility, and ensures policies are consistent with the values of all stakeholders. This C4 Article provides a unique opportunity to acquire broad stakeholder input on several key issues related to organ allocation policy. Contributors examined six issues selected by the editors, including who should determine organ allocation policy, which policies should be adopted to increase organ utilization, what is the minimal acceptable outcome for an organ transplant, what role should patient choice play in organ allocation policy, should nonmedical factors be used in organ allocation policy, and which policies should be advanced...
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