Abstract Background Donor-specific antibodies (DSAs) are common following lung transplantation (LuTx), yet their role in graft damage is inconclusive. Mean fluorescent intensity (MFI) is the main ...read-out of DSA diagnostics; however its value is often disregarded when analyzing unwanted post-transplant outcomes such as graft loss or chronic lung allograft dysfunction (CLAD). Here we aim to evaluate an MFI stratification method in these outcomes. Methods A cohort of 87 LuTx recipients has been analyzed, in which a cutoff of 8000 MFI has been determined for high MFI based on clinically relevant data. Accordingly, recipients were divided into DSA-negative, DSA-low and DSA-high subgroups. Both graft survival and CLAD-free survival were evaluated. Among factors that may contribute to DSA development we analyzed Pseudomonas aeruginosa (P. aeruginosa) infection in bronchoalveolar lavage (BAL) specimens. Results High MFI DSAs contributed to clinical antibody-mediated rejection (AMR) and were associated with significantly worse graft (HR: 5.77, p < 0.0001) and CLAD-free survival (HR: 6.47, p = 0.019) compared to low or negative MFI DSA levels. Analysis of BAL specimens revealed a strong correlation between DSA status, P. aeruginosa infection and BAL neutrophilia. DSA-high status and clinical AMR were both independent prognosticators for decreased graft and CLAD-free survival in our multivariate Cox-regression models, whereas BAL neutrophilia was associated with worse graft survival. Conclusions P. aeruginosa infection rates are elevated in recipients with a strong DSA response. Our results indicate that the simultaneous interpretation of MFI values and BAL neutrophilia is a feasible approach for risk evaluation and may help clinicians when to initiate DSA desensitization therapy, as early intervention could improve prognosis.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Extracellular vesicles (EV) are considered as a potential tool for early disease diagnosis; however, factors modifying EV release remain partially unknown. By using patient-derived organoids that ...capture the cellular heterogeneity of epithelial tissues, here we studied the connection between the Wnt-producing microniche and EV secretion in multiple tissues. Although nearly all cells in pancreatic ductal (PD) and pancreatic ductal adenocarcinoma (PDAC) samples expressed porcupine (PORCN), an enzyme critical for Wnt secretion, only a subpopulation of lung bronchiolar (NL) and lung adenocarcinoma (LUAD) organoid cells produced active Wnt. The microniche for proliferating cells was shaped not only by PORCN + cells in NL and LUAD organoids but also by fibroblast-derived EVs. This effect could be blocked by using Wnt secretion inhibitors. Whereas inhibiting Wnt secretion in PD NL or LUAD organoids critically changed both cell proliferation and EV release, these were uncoupled from each other in PDAC. Sorting for CD133 identified a cell population in the LUAD microniche that produced organoids with a high percentage of PORCN + and proliferating cells and an elevated EV secretion, which may explain that CD133 marks LUAD cells with malignant behavior. Collectively, we show here that high cell proliferation rate, induced by Wnt pathway activation, is coupled to a higher EV release, a critical finding that may be considered when developing EV-based diagnostic tools.
Both lung transplant recipients and candidates are characterised by reduced training capacity and low average quality of life (QoL). This review investigates the impact of training on exercise ...ability and QoL in patients before and after lung transplant.
Searches were conducted from the beginning to 7 March 2022 using the terms "exercise," "rehabilitation," "lung transplant," "exercise ability," "survival," "quality of life" and "telerehabilitation" in six databases, including Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, CINAHL, Nursing and Allied Health, and Scopus. The inclusion criteria were studies evaluating the effects of an exercise training programme concurrent with lung transplantation as well as patients and candidates (>18 years old) through any lung diseases. The term "lung transplant rehabilitation" was used to refer to all carefully thought-out physical activities with the ultimate or intermediate objective of improving or maintaining physical health.
Out of 1422 articles, 10 clinical- and 3 telerehabilitation studies, candidates (n = 420) and recipients (n = 116) were related to the criteria and included in this review. The main outcome significantly improved in all studies. The 6-min walk distance, maximum exercise capacity, peak oxygen uptake, or endurance for constant load rate cycling improved measuring physical activity aerobic exercises, breathing training, and aerobic and inspiratory muscle training sessions (IMT). Overall scores for dyspnoea improved after exercise training. Furthermore, health-related quality of life (HRQOL) also improved after aerobic exercise training, which was performed unsupervised or accompanied by breathing sessions. Aerobic training alone rather than combined with inspiratory muscle- (IMT) or breathing training enhanced exercise capacity.
In conclusion, rehabilitation programmes seem to be beneficial to patients both preceding and following lung transplantation. More studies are required to determine the best training settings in terms of time scale, frequency, and work intensity in terms of improving exercise ability, dyspnoea, and HRQOL.
Lung transplantation is the only successful treatment option for patients experiencing end-stage lung disease. Results have improved significantly in the last decade; however, the number one limiting ...factor is still the shortage of donor lungs. Due to the discrepancy between available donor lungs and patients awaiting lung transplantation, many centers have reintroduced donation after cardiac death (DCD). According to their results, DCD and donation after brain death (DBD) are comparable in terms of survival and graft function.
Currently in Hungary, donation is only allowed from DBD donors; however, due to the Eurotransplant agreement, non-heart-beating donation (NHBD) organs can be transplanted into Hungarian patients, and in some cases Hungarian transplant teams can also take part in NHBDs within the Eurotransplant region.
The Hungarian experience. A Hungarian patient received a lung from a 15-year-old uncontrolled DCD in Vienna. The donor was reanimated for 54 minutes and after lung procurement the lungs were put on ex vivo lung perfusion and later successfully implanted into the Hungarian recipient. The recovery was very successful and the patient is still alive.
The Hungarian Lung Transplantation Team was involved in a controlled Maastricht III donation in 2017. A 49-year-old female donor was reported from Ghent, Belgium. A multiorgan donation was carried out with 15 minutes of warm ischemic time in the case of the lungs.
DCD is an effective, safe, and available method to increase the donor pool. In the case of controlled donations, the necessary protocols have already been prepared. Although DBD is working very successfully in Hungary, infrastructural developments, education of professionals, and social preparations are all needed to implement a DCD protocol in Hungary.
After its initial difficulties were overcome, lung transplantation became an accepted and effective treatment for end-stage lung disease. Patients can take part in almost all kinds of sports after ...lung transplantation, including high-altitude mountaineering, which is an extreme sport even for healthy individuals. Several articles have been published about high-altitude tolerance of transplanted patients. However, this was the first high-altitude expedition that included only lung transplant patients.
The Vienna lung transplantation team organized an expedition in 2017 to conquer the peak of Mount Kilimanjaro, which consisted of 10 lung transplanted patients and 24 accompanying medical personnel. The participants were tested before and several times during the hike to evaluate their general and cardiopulmonary status, the severity of altitude sickness, and radio-morphologic changes. The results of the lung transplanted patients were compared to the results of their healthy companions.
The group started at 2360 meters and reached the 5895-meter-high summit of Mount Kilimanjaro after 6 days on June 18, 2017. Eight transplant patients and 24 escorting medical personnel reached the peak. This means that the success rate was 94%, which is significantly higher than the reported 85% for this route. The 2 transplant patients who did not make the summit turned back on the first and second day because they lacked the necessary fitness for the trip. We did not see a significant difference in the results regarding cardiopulmonary status or the severity of altitude sickness, although we observed mildly higher blood pressure and altitude sickness score results in the lung transplant group.
Based on our experiences, we can state that a stable patient after lung transplantation who attains the necessary physical fitness can achieve similar or even better physical results than an average healthy individual.
In this article we summarize the results of the first 3 years after launching the Hungarian Lung Transplantation Program.
The first lung transplant in Hungary was carried out on December 12, 2015, ...with the collaboration of the National Institute of Oncology and the Semmelweis University. Up to December 31, 2018, a total of 62 lung transplants were performed. Data were analyzed retrospectively. Patients were listed for lung transplant after the indication was established by the National Lung Transplantation Committee. Donor lungs were procured from brain-dead donors only.
Within this period our team was involved in 87 lung procurements, 61 of which resulted in bilateral lung transplant and 1 in single-sided transplant. The operative approach was unilateral thoracotomy (n = 1), bilateral thoracotomy (n = 1), or clamshell incision (n = 60) with venoarterial extracorporeal membrane oxygenation support. The underlying disease of the recipients was obstructive lung disease (n = 30), lung fibrosis (n = 11), cystic fibrosis (n = 18), primary pulmonary hypertension (n = 2), histiocytosis-X syndrome (n = 1), bronchiectasis (n = 2), lymphangioleiomyomatosis (n = 1), and retransplant because of bronchiolitis obliterans syndrome (n = 1). The youngest patient was 13 years of age, while the oldest was 65 years. Three patients died in the early postoperative phase. One-year survival was 80%.
The number of cases rises steadily in the Hungarian Lung Transplantation Program, which is exceptional compared with the start of other centrums. The incidence of complications and mortality is comparable with those of other experienced centers around the world. Our future goal is to broaden our waiting list, thus increasing the number of lung transplants carried out.
Abstract
OBJECTIVES: In the European Society of Thoracic Surgeons (ESTS) survey about management of malignant pleural effusions (MPE), 56% of respondents are not informed of any relevant clinical ...guidelines and 52%, who are aware of the existence of guidelines, declared that they are in need of updating or revision. The ESTS Pleural Diseases Working Group developed a benchmarking project on quality of previous guidelines on the management of MPE.
METHODS: The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument was used to assess each guideline. Each item was scored on a 7-point scale. Scores for each domain were calculated. Economic data for the nations which have issued the guidelines were collected from the Organisation for Economic Cooperation and Development health statistics database.
RESULTS: Six guidelines fitted the inclusion criteria and were assessed. Five out of 6 guidelines were produced by a multinational collaboration. Observers would recommend only 2 guidelines with minimal modification. Two areas that received the best score were clarity of presentation and scope and purpose (objectives and health questions target population). The applicability of guideline domain had the lowest score. Multivariate analysis demonstrated that clarity of presentation, international guidelines and publication through medical journal were related to improved scores. A strong correlation was observed between the measures of economic status.
CONCLUSIONS: The quality of guidelines assessed by the AGREE II criteria was found to be extremely variable. Guidelines achieving higher AGREE II scores were more likely to come from the European Union with the direct involvement of scientific societies in their development. It was also recognized that some fundamental unanswered questions remain about the management of MPE.
Introduction. Thymoma is the most common tumour of the anterior mediastinum. Video-Assisted Thoracic Surgery technique of thymoma resection is spreading world-wide, but the thoracoscopic method is ...still contentious in many ways. Authors evaluate the early and mid-term results of a 17 years period of VATS unilateral approach at 2 Hungarian thoracic surgical centers. Method. Depending on the anatomical situation of the thymoma, we performed thymectomy, or partial thymectomy (thymomectomy) for the Masaoka–Koga I–II–III stage thymoma from the right or left side through 2 or 3 intercostal ports. We managed the operations with ultrasonic dissector and electrocauter. By using international standards we evaluated perioperative morbidity, mid-term oncological results and clinical symptoms of myasthenia. Results. 23 of the 54 patients were man, 31 were woman, the average age was 58 (26–79) years, 23 of them had myasthenia. The conversion rate was 11,5% (7/61). The average operation time was 84 (39–150) minutes. The average hospitalisation time was 5.5 (3–19) days. The average size of the thymomas was 46 (18–90) mm. The histology resulted thymoma type A in 2 cases, AB in 19 cases, B1/2/3 in 11/11/1 cases, mixed B in 10 cases. The examination of the resection line was R0/1/2 in 42/11/1 cases. The Masaoka–Koga stages were: I (17), IIA (28), IIB (2), III (7). There was 25 thymomectomies, and 29 thymectomies. In seven cases there were extension of the operation to the pericardium (2), to the lung (2), to the phrenic nerve (6), and to innominate vein (1). The in-hospital mortality over 30 day was in 1 case (1.85%). The morbidity was 11/54 (20.4%). The average follow-up time was 62.56 (5–198) months. In the group with myasthenia the effectivity of the operation was 18/21 (85.7%), including complete remission of 5/21 (23.8%). Post-thymectomy myasthenia gravis developed in 2/31 cases (6.5%). The average 5 years survival was 100%, tumour-free 5 years survival was 96%. Conclusions. The higher proportion of the thymomectomy in the early results, higher conversion rate and lower R0 proportion might be in connection with the attitude of the surgeons, with the learning curve and with the limitations of the unilateral method. After a longer follow-up time late results may become more real and comparable. Instead of unilateral VATS technique we have changed to the subxyphoideal approach of VATS because of its better visualisation.
Introduction: Surgical technique of thymectomy performed for treatment of myasthenia gravis has considerably changed in the last almost 30 years. In addition to standard interventions – transsternal ...and transcervical thymectomy –, video-assisted thoracoscopic interventions (VATS), later on robotic surgery came into general use. In our two institutions, we apply VATS thymectomy since 2011. Methods: There are several different surgical techniques for this purpose; we approached the mediastinum through the right thoracic cavity. We prepared initially 3, later on 2 perimammal ports for the access of the thymus; the patients were in supine position during surgery. We used an ultrasonic cutting device in all cases. In order to perform extended thymectomy, we removed the fatty tissue around the thymus and opened widely the left thoracic cavity, too. During patient enrollment, we preferred patients with normal or lower body weight. Results: During 8 years and 4 months, we operated on 92 patients using this method for myasthenia gravis without thymoma; there were 20 male and 72 female patients at the age of 33 years on average (19–75 years). Duration of surgery was 35–160 minutes, 82.3 minutes on average. The bulky fatty tissue around the thymus made the orientation and the complete removal more difficult in a few patients. We experienced vascular injury in 4 cases and injury of the contralateral lung in 3 cases. Conversion was necessary in 2 cases (1 sternotomy and 1 thoracotomy), there were no nerve injuries. Assisted ventilation was necessary in case of ten patients in the postoperative period for a few hours; all other patients were extubated on the operating table. There was no need for repeated intubation and tracheostomy; there was no respiratory insufficiency and perioperative mortality. Duration of ICU care was 1.1 days on the average (0–11 days), that of the total hospital care 4.8 days on average (3–15 days). Duration of thoracic drainage was 1.16 days on average (1–4 days). Two patients (2.41%) died within one and five years after surgery. During 12–108 months (48 months on average) follow-up of 81 patients, 21 patients (25.3%) suffering from myasthenia total recovery was observed, pharmacologic remission was achieved in 4 patients (5.3%), minimal manifestation remained in 23 patients (24.1%), while in 28 patients (33.73%) other improvement was observed. The status of 4 patients (4.82%) remained unchanged and that of 4 patients (5.3%) worsened. Conclusion: VATS thymectomy represents a completely new surgical method for surgeons having experience in transsternal surgical technique. Bulky mediastinal fatty tissue makes surgery very difficult. The perioperative period is advantageous for the patients and also the long term follow-up results are acceptable. It is questionable that the thymus can be completely removed with this method in all cases.
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