Lung Transplantation in Hungary From Cardiac Surgeons' Perspective.

Thoracic organ transplantation made a fresh start in Hungary with the first double lung transplant in December 2015. This major leap in Hungarian transplantation was preceded by almost 10 years of preparation, new infrastructure development, and structural changes not only at the organizational level but in human resources as well. In the following years, until recently, altogether 47 lung transplants were performed on 24 men and 23 women. The underlying pathologies were as follows: chronic obstructive pulmonary disease, 25; cystic fibrosis, 11; idiopathic pulmonary fibrosis, 7; as well as other diseases, including bronchiectasis, eosinophilic granuloma, lymphangioleiomyomatosis, and primary pulmonary hypertension in 4 cases. The youngest recipient was 13 and the oldest was 65 years old. Overall survival rates at 30 days and at 1 year were 96% and 82%, respectively. No patients were lost in the cystic fibrosis and other diseases group, whereas the 1-year survival rates of the chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis groups were 73% and 71%, respectively. The results show the robustness and viability of the program, although there is still opportunity for further improvement. In this short paper, we summarize the fields of possible further cooperation of thoracic and cardiac teams as well as future challenges facing the new Hungarian lung transplant program.

Antibody-Mediated Rejection in a Multiple Lung Transplant Patient: A Case Report.

Lung transplant is an effective way to treat many end-stage lung diseases. However, one of the main barriers of allograft organ transplant is still the immunologic rejection of transplanted tissue, which is a response of the HLA molecules. Rejection is a complex process involving both T-cell-mediated delayed-type hypersensitivity reactions and antibody-mediated hypersensitivity reactions to histocompatibility molecules on foreign grafts. We report the case of a 25-year-old female patient with cystic fibrosis who underwent 2 lung transplants because of her initial diagnosis and appearance of bronchiolitis obliterans syndrome after the first transplant. Only 13 months after the second transplant, despite the therapies applied, a new rejection occurred associated with high mean fluorescent intensity donor-specific antibody levels, which resulted later in the death of the patient. The present case draws attention to the importance of matching HLA molecules between donor and recipient in addition to immunosuppressive therapy.

Launching the Hungarian Lung Transplantation Program.

The first successful lung transplantation was done in 1963 by James Hardy in the United States. The Vienna Lung Transplant program was launched in 1989 by Professor Walter Klepetko, and in 1996 lung transplantation became available in this center also for Hungarian patients. By 2013, conditions for full-scale Hungarian lung transplantation program were ripe. The Hungarian government invested 3 million Euros for infrastructural developments that made the operation and the perioperative care available. Besides funding, the professional training of medical personnel was also essential for this program to start. Hungarian specialists have had internship opportunities to study all aspects of lung transplantation at the Thoracic Surgery Department in Vienna. After successful preparations, the first lung transplantation in Hungary was performed on December 12, 2015.

Early Postoperative Problems After Lung Transplantation: First-Year Experiences in Light of the Newly Established National Hungarian Lung Transplantation Program.

Until December 2015, Hungarian patients' lung transplantations (LTXs) were done at the Medical University of Vienna. After several years of preparation, the National Hungarian Lung Transplantation Program was launched and the first milestone LTX was performed in Budapest on December 12, 2015. During the first 12 months, 18 lung transplantations took place in Hungary, including the first one. Data were retrospectively collected to analyze the early postoperative problems of the first 18 LTX patients of the newly launched Hungarian National Lung Transplantation Program. No patients with primary pulmonary hypertension and no children were transplanted during this period. We found that the postoperative problems of LTX differ from those of other huge thoracic surgeries both in a quantitative and a qualitative manner. We also reveal problems that are not present with other thoracic surgeries. The wide variety of problems during the early postoperative period after LTX can be managed by a highly organized and coordinated interdisciplinary teamwork.

Urgent Lung Transplantation in Severe Acute Respiratory Failure Based on Rapidly Progressive Interstitial Lung Disease: A Case Report.

Lung transplantation (LUTX) became a worldwide accepted standard therapy for certain well-defined chronic end-stage lung diseases. Until recently, patients on mechanical ventilation or extracorporeal life support techniques were hardly eligible for LUTX because of the inferior short-term results. However, a paradigm shift has occurred, and now these techniques represent bridging options to LUTX for listed patients. In the current practice, transplantation from the intensive care unit (ICU) is not extraordinary in patients on the waiting list. On the other hand, transplantation of an ICU patient who has previously been healthy without any chronic lung disease is still exceptional. Here we report a unique case of a 37-year-old woman without any relevant medical history who developed acute lung failure based on a cryptogenic organizing pneumonia. Her condition rapidly deteriorated and she required mechanical support, then she was bridged to transplantation on venovenous extracorporeal membrane oxygenation. She was listed for LUTX, and despite elevated panel-reactive antibody values, positive crossmatch LUTX was performed. Induction therapy, alemtuzumab, plasmapheresis, and intravenous immunoglobulin were administered. Her recovery was slow but finally she could be discharged from hospital in stable condition. After 2 months at home, she was readmitted to the hospital with respiratory failure from combined antibody-mediated rejection and infection. Before December 2015, the launch of Hungarian National Lung Transplantation Program, Hungarian patients were transplanted in Vienna. This case presents an exceptional example of national and international teamwork that aimed to save a young woman's life.

Soluble interleukin 6 (IL-6) receptor influences the expression of the protooncogene junB and the production of fibrinogen in the HepG2 human hepatoma cell line and primary rat hepatocytes.

Interleukin 6 (IL-6) belongs to a family of cytokines using receptors sharing a common signal-transducing chain, gp130 and containing a specific ligand-binding chain (IL-6R alpha). It was shown that both the membrane-bound and the soluble form (sIL-6R) of this ligand specific receptor chain occurs naturally. The soluble form of IL-6 receptor was found to be able to associate with the membrane-bound gp130 and to generate active IL-6 receptor complex capable of inducing signal transduction. This study on a human hepatoma cell line and primary rat hepatocytes examined how the effectiveness of IL-6 is modified by the presence of soluble IL-6 receptor and whether the sIL-6R in the absence of IL-6 acts on hepatocytes. The authors studied the gene expression of junB, a member of the Jun family of transcription factors, and the production of fibrinogen in response to IL-6 and sIL-6R. The data show that in hepatic cells, endogeneously expressing IL-6R, the IL-6 induced junB and fibrinogen expression is inhibited by the presence of sIL-6R. In addition we found that sIL-6R alone (in the absence of IL-6) induced junB mRNA expression, but had no effect on fibrinogen production.

[Interleukin-6 acts in different ways via soluble and membrane-bound receptors]. / Az interleukin-6 különbözöképpen fejti ki hatását szolubilis és membránreceptorán keresztül.

Interleukin-6 is a multifunctional cytokine participating in the regulation of several immunologic and other cell-physiological phenomena. It acts via a receptor consisting of two components, that besides the ligand-specific chain also contains a second component of 130 kD (gp 130). The soluble form of the ligand-specific component of this receptor was shown to occur physiologically in body fluids and -following the binding of interleukin-6-to be capable of associating with the membrane-bound receptor component and inducing signal-transduction. We studied the possible differences between the effects of interleukin-6 exerted via membrane-bound or soluble receptors on HepG2 human hepatoma and primary rat hepatocyte cultures. We used two methods to study the action of interleukin-6: the mRNA expression of the protooncogene junB as an early marker, and the protein production of fibrinogen as a late one. The effect of interleukin-6 on both cell types examined with both methods used was lower via the soluble than the membrane-bound receptor. In addition, the soluble receptors alone (without interleukin-6) could induce the expression of the junB gene. Considering the wide-spread biological and pathological activities of interleukin-6 these phenomena could have some role in the pathogenesis of some diseases.