Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study.

BACKGROUND: Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite. METHODS: A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 µg/kg) and epoetin beta (40,000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses. FINDINGS: We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after transplantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Postoperatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft. INTERPRETATION: Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome. FUNDING: European Commission, Knut and Alice Wallenberg Foundation, Swedish Research Council, StratRegen, Vinnova Foundation, Radiumhemmet, Clinigene EU Network of Excellence, Swedish Cancer Society, Centre for Biosciences (The Live Cell imaging Unit), and UCL Business.

[Lung Transplantation in Icelanders].

INTRODUCTION: Lung transplantation is a treatment option for end-stage lung diseases, excluding lung cancer, when life expectancy is short and quality of life is poor. In most instances pulmonary function and quality of life improves after lung transplantation. Infections and rejection are the most common complications and limit the feasibility of lung transplantation. MATERIALS AND METHODS: Retrospective analysis of lung transplantations performed on Icelanders from February 1988 to January 2015. Clinical information was obtained from medical records and a database was created. Information on demographics, underlying lung disease, type of transplantation, immunosuppression, rejection and other complications was collected. RESULTS: A total of 21 lung transplantations were performed, one of which was a retransplantation. There were 9 females and 11 males and the mean age was 45 years (20-61 years). Most of the operations were done at the Sahlgrenska hospital in Gothenburg. Bilateral lung transplantion was the most common operation. COPD was the most common indication. Rejection and infections were the most common complications. Eight of 20 patients have had acute rejection and half of the patients chronic rejection. Six of 20 patients are deceased, three died from chronic rejection. Median survival is 8,5 years. Five-year survival is 74%. CONCLUSIONS: Lung transplantations are currently performed at the Sahlgrenska hospital in Gothenburg but follow-up is in the hands of specialized pulmonologists in Iceland. Complications and survival for Icelandic patients is similar to larger centers. Close cooperation with the transplanting center is essential. KEY WORDS: lung transplantation, Icelanders, indications, survival, complications.

[Evaluation of thromboprophylactic therapy at Landspítali - The National University Hospital of Iceland; a cross-sectional study on acute wards]. / Frammistada Landspitala i forvornum gegn blaaedasegasjukdomum; thversnidsrannsokn a bradadeildum.

OBJECTIVE: Venous thromboembolic disease is a serious and often fatal complication following hospital admission. Studies show that thromboprophylactic therapy for this condition is often underutilized. The aim of this study was to evaluate the performance of thromboprophylactic therapy at Landspítali - The University Hospital of Iceland in adult patients admitted to acute wards. METHODS AND MATERIALS: On 2 December 2009 hospital charts of admitted patients on acute wards were reviewed and assessed for appropriate thromboprophylactic treatment according to the 2008 guidelines from The American College of Chest Physicians. The results were compared to those of other countries from the multinational Endorse study from 2008. RESULTS: 251 patient were included of whom 47% were considered at risk for venous thromboembolic disease. Of those 57% received appropriate thromboprophylactic treatment or 78% of surgical and 26% of medical patients. CONCLUSIONS: Adherence to clinical guidelines for thromboprophylactic treatment at surgical wards of Landspítali - The National University Hospital of Iceland was good and well above the average compared to the results of the Endorse study. Performance on the medical wards was on the other hand below average. Our results show that application of thromoboprophylactic treatment at Landspítali could be improved and thereby enhance patient safety.