Orthotopic transplantation of the bioengineered lung using a mouse-scale perfusion-based bioreactor and human primary endothelial cells.

Whole lung engineering and the transplantation of its products is an ambitious goal and ultimately a viable solution for alleviating the donor-shortage crisis for lung transplants. There are several limitations currently impeding progress in the field with a major obstacle being efficient revascularization of decellularized scaffolds, which requires an extremely large number of cells when using larger pre-clinical animal models. Here, we developed a simple but effective experimental pulmonary bioengineering platform by utilizing the lung as a scaffold. Revascularization of pulmonary vasculature using human umbilical cord vein endothelial cells was feasible using a novel in-house developed perfusion-based bioreactor. The endothelial lumens formed in the peripheral alveolar area were confirmed using a transmission electron microscope. The quality of engineered lung vasculature was evaluated using box-counting analysis of histological images. The engineered mouse lungs were successfully transplanted into the orthotopic thoracic cavity. The engineered vasculature in the lung scaffold showed blood perfusion after transplantation without significant hemorrhage. The mouse-based lung bioengineering system can be utilized as an efficient ex-vivo screening platform for lung tissue engineering.

Long-term survival and clinical outcomes of delayed chest closure following lung transplantation.

PURPOSES: Delayed chest closure (DCC) is a widely accepted procedure in the context of lung transplantation (LTx); yet there are few reports detailing its long-term survival and clinical outcomes. METHODS: We reviewed the medical records of recipients who underwent deceased-donor lung transplantation (LTx) at Tohoku University Hospital. Long-term survival, including overall survival, freedom from chronic lung allograft dysfunction (CLAD), and CLAD-free survival and the clinical outcomes of graft function and physical performance and constitution were reviewed in recipients with DCC. RESULTS: Between 2009 and 2022, 116 patients underwent LTx, 33 of whom (28.4%) required DCC. The intra-and post-operative courses of the recipients who required DCC were more complicated than those of the recipients who underwent primary chest closure (PCC), with frequent volume reduction surgery and longer periods of invasive mechanical ventilation. Pulmonary vascular disease was considered a risk factor for these complications and DCC. Nonetheless, long-term survival and graft functions were comparable between the DCC and PCC groups. The physical performance and constitution of recipients who required DCC continued to improve, and by 2 years after transplantation, exhibited almost no difference from those who underwent PCC. CONCLUSIONS: In view of the profoundly complicated intra- and post-operative courses, DCC should be performed cautiously and only when clinically indicated, despite which it can result in equivalent long-term survival and acceptable outcomes to PCC.

Systemic-to-pulmonary artery shunt treated with transcatheter arterial embolization and subsequent lung segmentectomy.

BACKGROUND: Systemic-to-pulmonary artery shunt (SPAS) is a rare condition that can occur as a result of congenital heart disease or chronic pulmonary inflammation, occasionally leading to life-threatening hemoptysis. Computed tomography (CT) imaging is crucial in the diagnosis of SPAS, and the optimal management approach for SPAS remains uncertain. This case report presents a novel approach to the treatment of SPAS, consisting of transcatheter arterial embolization of the systemic artery followed by lung segmentectomy. CASE PRESENTATION: A 42-year-old man with abnormal chest findings was referred to us and a diagnosis of SPAS was established based on the CT findings showing a blood flow regurgitation from the dilated left 4th intercostal artery to the Lt. A6. The patient was asymptomatic but we decided to treat him to prevent a risk of future hemoptysis. Transcatheter arterial embolization (TAE) of systemic arteries followed by S6 segmentectomy was successfully performed with minimal blood loss and complete removal of the dilated intra-pulmonary blood vessels. Histological analysis confirmed the diagnosis of SPAS. CONCLUSION: We reported a case of SPAS, who was successfully treated with the combination of TAE and subsequent segmentectomy. The blood loss during surgery was minimal and this strategy appeared to minimize future recanalization and hemoptysis. Further studies and long-term follow-up of SPAS patients are required to establish standardized management guidelines for this rare condition.

Outcome and prognostic factors after lung transplantation for bronchiectasis other than cystic fibrosis.

BACKGROUND: While lung transplant (LTX) can be an effective therapy to provide the survival benefit in selected populations, post-transplant outcome in LTX recipients with bronchiectasis other than cystic fibrosis (CF) has been less studied. Pseudomonas aeruginosa, often associated with exacerbations in bronchiectasis, is the most common micro-organism isolated from LTX recipients. We aimed to see the outcomes of patients with bronchiectasis other than CF after LTX and seek the risk factors associated with pre- and post-transplant Pseudomonas status. METHODS: Patients who underwent LTX at Tohoku University Hospital between January 2000 and December 2020 were consecutively included into the retrospective cohort study. Pre- and post-transplant prevalence of Pseudomonas colonization between bronchiectasis and other diseases was reviewed. Post-transplant outcomes (mortality and the development of chronic lung allograft dysfunction (CLAD)) were assessed using a Cox proportional hazards and time-to-event outcomes were estimated using the Kaplan-Meier method. RESULTS: LTX recipients with bronchiectasis experienced a high rate of pre- and post-transplant Pseudomonas colonization compared to other diseases with statistical significance (p < 0.001 and p < 0.001, respectively). Nevertheless, long-term survival in bronchiectasis was as great as non-bronchiectasis (Log-rank p = 0.522), and the bronchiectasis was not a trigger for death (HR 1.62, 95% CI 0.63-4.19). On the other hand, the chance of CLAD onset in bronchiectasis was comparable to non-bronchiectasis (Log-rank p = 0.221), and bronchiectasis was not a predictor of the development of CLAD (HR 1.88, 95% CI 0.65-5.40). CONCLUSIONS: Despite high prevalence of pre- and post-transplant Pseudomonas colonization, the outcome in LTX recipients with bronchiectasis other than CF was comparable to those without bronchiectasis.

High Prevalence of Acute Exacerbation of Interstitial Lung Disease in Japanese Patients with Systemic Sclerosis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by extensive fibrosis and autoantibodies. Its clinical manifestations are diverse and include Raynaud's phenomenon, gastrointestinal dysmotility, interstitial lung disease (ILD), pulmonary hypertension, and renal crisis. Among these, ILD is the primary cause of SSc-related death. It has been considered that acute exacerbation of ILD (AE-ILD) is not common in patients with SSc; however, little is known about the prevalence of AE-ILD in Japanese patients with SSc. In this study, we aimed to clarify the prevalence, clinical characteristics, and prognosis of patients with SSc who developed AE-ILD and to identify predictive factors for AE-ILD in our Japanese cohorts. Clinical data of patients who visited our department from 1990 to 2014 and fulfilled the 2013 classification criteria for SSc were retrospectively reviewed. A total of 139 patients were enrolled. The mean age of onset was 49.1 years, and 113 (81.3%) patients were female; 116 (83.5%) had limited cutaneous involvement, and the overall 10-year survival rate was 92.0%. Among 66 (47.5%) patients with ILD, 13 (9.4%) developed AE-ILD. Patients with AE-ILD had a significantly higher incidence of overlap with polymyositis (PM) or dermatomyositis (DM) and lower prevalence of anticentromere antibodies with higher mortality rate compared with those without AE-ILD. Multivariate Cox regression analysis identified that an overlap with PM or DM was the most significant predictive factor for AE-ILD. Our study results suggest that Japanese patients with SSc, particularly patients overlapped with PM or DM, have a high risk of AE-ILD.

Synovitis in a Patient with IgG4-related Disease.

A 71-year-old man was admitted to our department due to arthralgia and renal dysfunction. A physical examination disclosed swelling of the right shoulder and left wrist joints. Laboratory tests showed elevated serum IgG4 and creatinine levels, and magnetic resonance imaging of the wrist revealed bone erosion and synovitis. In addition, fluorodeoxyglucose positron emission tomography showed uptake in the submandibular glands, pancreas, kidneys, and affected joints and a renal biopsy revealed tubulointerstitial nephritis with the infiltration of IgG4+ plasma cells. The patient was subsequently diagnosed with IgG4-related disease (IgG4-RD) and successfully treated with corticosteroid therapy. This case suggests that erosive arthritis may occur in patients with IgG4-RD.