A Comprehensive Review on the Surgical Aspect of Lung Transplant Models in Mice and Rats

Lung transplantation improves the outcome and quality of life of patients with end-stage pulmonary disease. However, the procedure is still hampered by the lack of suitable donors, the complexity of the surgery, and the risk of developing chronic lung allograft dysfunction. Over the past decades, translational experiments in animal models have led to a better understanding of physiology and immunopathology following the lung transplant procedure. Small animal models (e.g., rats and mice) are mostly used in experiments regarding immunology and pathobiology and are preferred over large animal models due to the ethical aspects, the cost-benefit balance, and the high throughput possibility. In this comprehensive review, we summarize the reported surgical techniques for lung transplantation in rodent models and the management of perioperative complications. Furthermore, we propose a guide to help identify the appropriate species for a given experiment and discuss recent experimental findings in small animal lung transplant models

Controlled Hypothermic Storage for Lung Preservation: Leaving the Ice Age Behind

Controlled hypothermic storage (CHS) is a recent advance in lung transplantation (LTx) allowing preservation at temperatures higher than those achieved with traditional ice storage. The mechanisms explaining the benefits of CHS compared to conventional static ice storage (SIS) remain unclear and clinical data on safety and feasibility of lung CHS are limited. Therefore, we aimed to provide a focus review on animal experiments, molecular mechanisms, CHS devices, current clinical experience, and potential future benefits of CHS. Rabbit, canine and porcine experiments showed superior lung physiology after prolonged storage at 10°C vs. ≤4°C. In recent molecular analyses of lung CHS, better protection of mitochondrial health and higher levels of antioxidative metabolites were observed. The acquired insights into the underlying mechanisms and development of CHS devices allowed clinical application and research using CHS for lung preservation. The initial findings are promising; however, further data collection and analysis are required to draw more robust conclusions. Extended lung preservation with CHS may provide benefits to both recipients and healthcare personnel. Reduced time pressure between procurement and transplantation introduces flexibility allowing better decision-making and overnight bridging by delaying transplantation to daytime without compromising outcome

Gamma-glutamyltransferase is a strong predictor of secondary sclerosing cholangitis after lung transplantation for COVID-19 ARDS

Background: Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown. Methods: This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis. Results: A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the ‘SSC’ group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of ‘SSC’ patients was severely impaired compared to ‘no SSC’ patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004). Conclusions: SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing

Lung transplantation following controlled hypothermic storage with a portable lung preservation device: first multicenter European experience

IntroductionCompared with traditional static ice storage, controlled hypothermic storage (CHS) at 4–10°C may attenuate cold-induced lung injury between procurement and implantation. In this study, we describe the first European lung transplant (LTx) experience with a portable CHS device.MethodsA prospective observational study was conducted of all consecutively performed LTx following CHS (11 November 2022 and 31 January 2024) at two European high-volume centers. The LUNGguard device was used for CHS. The preservation details, total ischemic time, and early postoperative outcomes are described. The data are presented as median (range: minimum–maximum) values.ResultsA total of 36 patients underwent LTx (i.e., 33 bilateral, 2 single LTx, and 1 lobar). The median age was 61 (15–68) years; 58% of the patients were male; 28% of the transplantations had high-urgency status; and 22% were indicated as donation after circulatory death. In 47% of the patients, extracorporeal membrane oxygenation (ECMO) was used for perioperative support. The indications for using the CHS device were overnight bridging (n = 26), remote procurement (n = 4), rescue allocation (n = 2), logistics (n = 2), feasibility (n = 1), and extended-criteria donor (n = 1). The CHS temperature was 6.5°C (3.7°C–9.3°C). The preservation times were 11 h 18 (2 h 42–17 h 9) and 13 h 40 (4 h 5–19 h 36) for the first and second implanted lungs, respectively, whereas the total ischemic times were 13 h 38 (4 h 51–19 h 44) and 15 h 41 (5 h 54–22 h 48), respectively. The primary graft dysfunction grade 3 (PGD3) incidence rates were 33.3% within 72 h and 2.8% at 72 h. Intensive care unit stay was 8 (4–62) days, and the hospital stay was 28 (13–87) days. At the last follow-up [139 (7–446) days], three patients were still hospitalized. One patient died on postoperative day 7 due to ECMO failure. In-hospital Clavien–Dindo complications of 3b were observed in six (17%) patients, and 4a in seven (19%).ConclusionCHS seems safe and feasible despite the high-risk recipient and donor profiles, as well as extended preservation times. PGD3 at 72 h was observed in 2.8% of the patients. This technology could postpone LTx to daytime working hours. Larger cohorts and longer-term outcomes are required to confirm these observations

Lung resection after pneumonectomy: is it worth the risk?

According to the National Cancer Database between 2004 and 2013, pneumonectomy for non-small cell lung cancer (NSCLC) (n=79,953 patients) accounted for 5 percent of all resections (1). After successful treatment however, patients remain at risk (1–5%) for developing malignant lesions (recurrence or second primary) in the contralateral lung (2,3). Although—for resectable lesions—cure could be attained by surgery, the previous contralateral lung resection is a relative (but no absolute) contra-indication for which the risk-benefit ratio of every case should be discussed multidisciplinary. Outcome after post-pneumonectomy lung resection has improved over the last years due to improvement in surveillance techniques [positron emission tomography-computed tomography (PET-CT)] resulting in early diagnosis, careful selection of surgical candidates, advances in anaesthesiology and increasing experience with minimal invasive surgical techniques. In this paper we review these improvements and summarize the reported outcome of the largest reported single-center series.status: Published onlin

A case report of peritoneal tuberculosis diagnosed by laparoscopy in a low prevalence setting

Peritoneal tuberculosis is a rare extrapulmonary manifestation of tuberculosis. Considering the diagnosis of peritoneal tuberculosis in a low prevalence setting can be vital for further clinical management in selected patients. In a young male with migration background, presenting with generalised abdominal pain, computed tomography revealed ascites, omental and peritoneal thickening and enlarged mesentery lymph nodes. Computed tomography also revealed a distal ureteral calculus at the right vesico-ureteral junction. Diagnostic laparoscopy showed a nodular degeneration of the visceral and parietal peritoneum and adhesions in the upper peritoneal cavity. Tissue biopsy of peritoneal lesions and omentum was performed. Histological examination revealed granulomas with central caseating necrosis. The ureteral stone was removed by means of ureteroscopy. Prompt diagnosis of peritoneal TB made possible to start anti-tuberculous chemotherapy without significant delay. The low prevalence of peritoneal TB demands a high index of suspicion in patients at risk presenting with nonspecific abdominal complaints, ascites and constitutional symptoms. Diagnostic laparoscopy leads to a quick diagnosis by direct visualisation of the peritoneal cavity and tissue biopsy. When available, it is the diagnostic procedure of choice to confirm tuberculous peritonitis. The concomitant presentation of tuberculous peritonitis and ureteral calculus can be explained by hypercalciuria in granulomatous disease.status: publishe

Iterative correction of beam hardening artifacts in CT

Purpose. To reduce beam hardening artifacts in CT in case of an unknown X-ray spectrum and unknown material properties. Methods. We assume that the object can be segmented into a few materials with different attenuation coefficients, and parameterize the spectrum using a small number of energy bins. The corresponding unknown spectrum parameters and material attenuation values are estimated by minimizing the difference between the measured sinogram data and a simulated polychromatic sinogram. Three iterative algorithms are derived from this approach: two reconstruction algorithms IGR and IFR, and one sinogram precorrection method ISP. Results. The methods are applied on real X-ray data of a high and a low-contrast phantom. All three methods successfully reduce the cupping artifacts caused by the beam polychromaticity in such a way that the reconstruction of each homogeneous region is to good accuracy homogeneous, even in case the segmentation of the preliminary reconstruction image is poor. In addition, the results show that the three methods tolerate relatively large variations in uniformity within the segments. Conclusions. We show that even without prior knowledge about materials or spectrum, effective beam hardening correction can be obtained.status: publishe