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INTRODUCTION: Carbon monoxide (CO) has been shown to exert protective effects in multiple organs following ischemic injury, including the lung. The purpose of this study was to examine the effects of CO administration during ex vivo lung perfusion (EVLP) on lung grafts exposed to prolonged cold ischemia. METHODS: Ten porcine lungs were subjected to 18 h of cold ischemia followed by 6 h of EVLP. Lungs were randomized to EVLP alone (control, n = 5) or delivery of 500 ppm of CO during the 1st hour of EVLP (treatment, n = 5). Following EVLP, the left lungs were transplanted and reperfused for 4 h. RESULTS: At the end of EVLP, pulmonary vascular resistance (P = 0.007) and wet to dry lung weight ratios (P = 0.027) were significantly reduced in CO treated lungs. Posttransplant, lung graft PaO2/FiO2 (P = 0.032) and compliance (P = 0.024) were significantly higher and peak airway pressure (P = 0.032) and wet to dry ratios (P = 0.003) were significantly lower in CO treated lungs. Interleukin-6 was significantly reduced in plasma during reperfusion in the CO treated group (P = 0.040). CONCLUSIONS: In this preclinical porcine model, CO application during EVLP resulted in better graft performance and outcomes after reperfusion.
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Background: Marijuana use has become more common since its legalization, as have reports of marijuana-associated spontaneous pneumomediastinum. Non-spontaneous causes such as esophageal perforation are often ruled out on presentation due to the severe consequences of untreated disease. Here we seek to characterize the presentation of marijuana-associated spontaneous pneumomediastinum and explore whether esophageal imaging is necessary in the setting of an often benign course and rising healthcare costs. Materials and Methods: Retrospective review was performed for all 18-55 year old patients evaluated at a tertiary care hospital between 1/1/2008 and 12/31/2018 for pneumomediastinum. Iatrogenic and traumatic causes were excluded. Patients were divided into marijuana and control groups. Results: 30 patients met criteria, with 13 patients in the marijuana group. The most common presenting symptoms were chest pain/discomfort and shortness of breath. Other symptoms included neck/throat pain, wheezing, and back pain. Emesis was more common in the control group but cough was equally prevalent. Leukocytosis was present in most patients. Four out of eight of computed tomography esophagarams in the control group showed a leak requiring intervention, while only one out of five in the marijuana group showed even a possible subtle extravasation of contrast but this patient ultimately was managed conservatively given the clinical picture. All standard esophagrams were negative. All marijuana patients were managed without intervention. Discussion: Marijuana-associated spontaneous pneumomediastinum appears to have a more benign clinical course compared to non-spontaneous pneumomediastinum. Esophageal imaging did not change management for any marijuana cases. Perhaps such imaging could be deferred if clinical presentation of pneumomediastinum in the setting of marijuana use is not suggestive of esophageal perforation. Further research into this area is certainly worth pursuing.
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OBJECTIVE: Acceptance of lungs from donation after circulatory determination of death has been generally restricted to donors who have cardiac arrest within 60 minutes after withdrawal of life-sustaining therapies. We aimed to determine the effect of the interval between withdrawal of life-sustaining therapies to arrest and recipient outcomes. Second, we aimed to compare outcomes between donation after circulatory determination of death transplants and donation after neurologic determination of death transplants. METHODS: A single-center, retrospective review was performed analyzing the clinical outcomes of transplant recipients who received donation after circulatory determination of death lungs and those who received donation after neurologic determination of death lungs. Donation after circulatory determination of death cases were then grouped on the basis of the interval between withdrawal of life-sustaining therapies and asystole: 0 to 19 minutes (rapid), 20 to 59 minutes (intermediate), and more than 60 minutes (long). Recipient outcomes from each of these groups were compared. RESULTS: A total of 180 cases of donation after circulatory determination of death and 1088 cases of donation after neurologic determination of death were reviewed between 2007 and 2017. There were no significant differences in the 2 groups in terms of age, gender, recipient diagnosis, and type of transplant (bilateral vs single). Ex vivo lung perfusion was used in 118 of 180 (65.6%) donation after circulatory determination of death cases and 149 of 1088 (13.7%) donation after neurologic determination of death cases before transplantation. The median survivals of recipients who received donation after circulatory determination of death lungs versus donation after neurologic determination of death lungs were 8.0 and 6.9 years, respectively. Time between withdrawal of life-sustaining therapies and asystole was available for 148 of 180 donors (82.2%) from the donation after circulatory determination of death group. Mean and median time from withdrawal of life-sustaining therapies to asystole were 28.6 minutes and 16 minutes, respectively. Twenty donors required more than 60 minutes to experience cardiac arrest, with the longest duration being 154 minutes before asystole was recorded. Recipients of donation after circulatory determination of death lungs who had cardiac arrest at 0 to 19 minutes (90 donors), 20 to 59 minutes (38 donors), and more than 60 minutes (20 donors) did not demonstrate any significant differences in terms of short- and long-term survivals, primary graft dysfunction 2 and 3, intensive care unit stay, mechanical ventilation days, or total hospital stay. CONCLUSIONS: Short- and long-term outcomes in recipients who received donation after neurologic determination of death versus donation after circulatory determination of death lungs are similar. Different withdrawals of life-sustaining therapies to arrest intervals were not associated with recipient outcomes. The maximum acceptable duration of this interval has yet to be established.
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Parada Cardíaca , Pneumopatias/mortalidade , Pneumopatias/cirurgia , Transplante de Pulmão , Disfunção Primária do Enxerto/epidemiologia , Obtenção de Tecidos e Órgãos , Adulto , Idoso , Cuidados Críticos , Feminino , Sobrevivência de Enxerto , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Suspensão de TratamentoRESUMO
BACKGROUND: There are limited therapeutic options directed at the underlying pathological processes in acute respiratory distress syndrome (ARDS). Experimental therapeutic strategies have targeted the protective systems that become deranged in ARDS such as surfactant. Although results of surfactant replacement therapy (SRT) in ARDS have been mixed, questions remain incompletely answered regarding timing and dosing strategies of surfactant. Furthermore, there are only few truly clinically relevant ARDS models in the literature. The primary aim of our study was to create a clinically relevant, reproducible model of severe ARDS requiring extracorporeal membrane oxygenation (ECMO). Secondly, we sought to use this model as a platform to evaluate a bronchoscopic intervention that involved saline lavage and SRT. METHODS: Yorkshire pigs were tracheostomized and cannulated for veno-venous ECMO support, then subsequently given lung injury using gastric juice via bronchoscopy. Animals were randomized post-injury to either receive bronchoscopic saline lavage combined with SRT and recruitment maneuvers (treatment, n = 5) or recruitment maneuvers alone (control, n = 5) during ECMO. RESULTS: PaO2/FiO2 after aspiration injury was 62.6 ± 8 mmHg and 60.9 ± 9.6 mmHg in the control and treatment group, respectively (p = 0.95) satisfying criteria for severe ARDS. ECMO reversed the severe hypoxemia. After treatment with saline lavage and SRT during ECMO, lung physiologic and hemodynamic parameters were not significantly different between treatment and controls. CONCLUSIONS: A clinically relevant severe ARDS pig model requiring ECMO was established. Bronchoscopic saline lavage and SRT during ECMO did not provide a significant physiologic benefit compared to controls.
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A large proportion of controlled donation after circulatory death (cDCD) donor lungs are declined because cardiac arrest does not occur within a suitable time after the withdrawal of life-sustaining therapy. Improved strategies to preserve lungs after asystole may allow the recovery team to arrive after death actually occurs and enable the recovery of lungs from more cDCD donors. The aim of this study was to determine the effect of donor positioning on the quality of lung preservation after cardiac arrest in a cDCD model. Cardiac arrest was induced by withdrawal of ventilation under anesthesia in pigs. After asystole, animals were divided into 2 groups based on body positioning (supine or prone). All animals were subjected to 3 hours of warm ischemia. After the observation period, donor lungs were explanted and preserved at 4°C for 6 hours, followed by 6 hours of physiologic and biological lung assessment under normothermic ex vivo lung perfusion. Donor lungs from the prone group displayed significantly greater quality as reflected by better function during ex vivo lung perfusion, less edema formation, less cell death, and decreased inflammation compared with the supine group. A simple maneuver of donor prone positioning after cardiac arrest significantly improves lung graft preservation and function.
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Transplante de Pulmão , Pulmão/fisiopatologia , Preservação de Órgãos/métodos , Decúbito Ventral , Traumatismo por Reperfusão/prevenção & controle , Doadores de Tecidos/provisão & distribuição , Isquemia Quente , Animais , Morte , Circulação Extracorpórea , SuínosRESUMO
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.
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Lesão Pulmonar Aguda/cirurgia , Hepacivirus/efeitos da radiação , Hepatite C/prevenção & controle , Transplante de Pulmão , Pulmão/virologia , Complicações Pós-Operatórias/prevenção & controle , Inativação de Vírus/efeitos da radiação , Animais , Modelos Animais de Doenças , Hepacivirus/fisiologia , Hepatite C/virologia , Humanos , Masculino , Fototerapia , Complicações Pós-Operatórias/virologia , Suínos , Doadores de TecidosRESUMO
OBJECTIVE: The efficacy of radiofrequency ablation (RFA) for symptomatic varicose veins is well established. Alternatively, there is less consensus and little data on outcomes when treating great saphenous veins (GSV) of small diameter (≤5 mm). The purpose of this study is to assess clinical and anatomical outcomes of RFA on symptomatic patients with small GSV. METHODS: A retrospective analysis was performed on our symptomatic patients who received RFA of incompetent GSV without any concomitant adjunctive procedures between January 2008 and December 2011. Limbs with GSV thigh diameter ≤5 mm and >5 mm on duplex while standing were subject to review. Clinical success was defined as an improvement in Venous Clinical Severity Score (VCSS) at 3 months. Anatomic success was defined as absence of venous flow ≤3 cm distal to the saphenofemoral junction on duplex ultrasound examination. Changes in CEAP class were noted. RESULTS: In 307 patients, 55 limbs in 44 patients met inclusion criteria. Baseline median VCSS was 4 (interquartile range [IQR], 4, 5) for those patients with diameter ≤5 mm. Clinical success was seen in 83% of limbs at 3 months with a median VCSS change of -2 (IQR, -3, -1). None of the treated limbs had phlebectomy for symptomatic refluxing GSV varicosities prior to 3-month follow up. One phlebectomy was performed for cosmesis at 78 days postprocedure. Anatomic success was achieved in 96% of limbs at 3 months. Baseline median CEAP was 2 (IQR, 2, 2). The median CEAP change at 3 months was 0 (IQR, -1, 0). One patient experienced thrombus extension into the saphenofemoral junction at 4 days. CONCLUSIONS: In our experience, RFA of symptomatic small-diameter GSV provides comparable clinical and anatomic outcomes to that of current published data. Our findings suggest that these patients benefit clinically from RFA.