Lung donation after circulatory death

PURPOSE OF REVIEW The current review presents a concise update on published literature on donation after circulatory death (DCD) and lung transplantation (LTx). Worldwide an increasing need for lungs is evident, however the utilization rate of DCD lung donors is still considerably low. In this summary article, we reviewed both the experimental background and international clinical experience. RECENT FINDINGS Our analysis confirmed satisfactory results for LTx from DCD donors, which equals the results from donation after brain death. Although most studies reported on short-term results, some confirmed these results on the long-term and development of chronic lung allograft dysfunction. Our review summarizes the different DCD categories and underlines the potential of the DCD V category. We analyze the barriers to implement a DCD program, discuss the more recent advances like ex-vivo lung perfusion and describe the future challenges. SUMMARY Based on the current short-term and long-term clinical results, we believe that barriers for DCD utilization should be overcome, resulting in a safe implementation of more DCD LTx programs worldwide. VIDEO ABSTRACT

Unusual cause of mechanical ileus: abdominal cocoon syndrome

A 38-year-old black male patient was admitted with diarrhea and nausea over two days and aggravating pain in the meso- and epigastium that resolved after urination. He had no surgical history and only an episode of pulmonary tuberculosis five years earlier, for which he was properly treated. Physical examination revealed a tender and distended abdomen with clangorous sounds. His temperature was 36.1°C. Routine laboratory blood analyses were normal. An abdominal ultrasound revealed diffuse distention of the small intestine. A computed tomography (CT) scan showed a conglomerate of dilated small bowel loops in the meso- and hypogastrium, suggestive for a supravesical mechanical small bowel obstruction. Peritoneal thickening was seen in the right epigastrium (Figure A, white arrow). An explorative laparoscopy revealed a whitish, thickened membrane encapsulating the small bowels as a ‘cocoon’ (Figure B). Extensive adhesiolysis released an intestinal kinking in the lower abdomen, just above the bladder. No resection was needed. Histopathology of the membrane showed fibrocollagenous tissue with mixed inflammatory infiltrate

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

Paneth Cell Alterations During Ischemia-reperfusion, Follow-up, and Graft Rejection After Intestinal Transplantation

BACKGROUND Ischemia-reperfusion (IR) injury is inevitable during intestinal transplantation (ITx) and executes a key role in the evolution towards rejection. Paneth cells (PC) are crucial for epithelial immune defense and highly vulnerable to IR injury. We investigated the effect of ITx on PC after reperfusion (T0), during follow-up, and rejection. Moreover, we investigated whether PC loss was associated with impaired graft homeostasis. METHODS Endoscopic biopsies, collected according to center-protocol and at rejection episodes, were retrospectively included (n=28 ITx, n=119 biopsies) Biopsies were immunohistochemically co-stained for PC (lysozyme) and apoptosis, and PC/crypt and lysozyme intensity were scored. RESULTS We observed a decrease in PC/crypt and lysozyme intensity in the first week after ITx (W1) compared to T0. There was a tendency towards a larger decline in PC/crypt (p=0.08) and lysozyme intensity (p=0.08) in W1 in patients who later developed rejection compared to patients without rejection. Follow-up biopsies showed that the PC number recovered, whereas lysozyme intensity remained reduced. This persisting innate immune defect may contribute to the well-known vulnerability of the intestine to infection. There was no clear evidence that PC were affected throughout rejection. CONCLUSION This study revealed a transient fall in PC numbers in the early post-ITx period, but a permanent reduction in lysozyme intensity following ITx. Further research is needed to determine the potential clinical impact of PC impairment after ITx

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

Allogeneic Hematopoietic Stem Cell Transplantation After Prior Lung Transplantation for Hereditary Pulmonary Alveolar Proteinosis: A Case Report

Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disorder characterized by surfactant accumulation in the small airways due to defective clearance by alveolar macrophages, resulting in impaired gas exchange. Whole lung lavage is the current standard of care treatment for PAP. Lung transplantation is an accepted treatment option when whole lung lavage or other experimental treatment options are ineffective, or in case of extensive pulmonary fibrosis secondary to PAP. A disadvantage of lung transplantation is recurrence of PAP in the transplanted lungs, especially in hereditary PAP. The hereditary form of PAP is an ultra-rare condition caused by genetic mutations in genes encoding for the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, and intrinsically affects bone marrow derived-monocytes, which differentiate into macrophages in the lung. Consequently, these macrophages typically display disrupted GM-CSF receptor-signaling, causing defective surfactant clearance. Bone marrow/hematopoietic stem cell transplantation may potentially reverse the lung disease in hereditary PAP. In patients with hereditary PAP undergoing lung transplantation, post-lung transplant recurrence of PAP may theoretically be averted by subsequent hematopoietic stem cell transplantation, which results in a graft-versus-disease (PAP) effect, and thus could improve long-term outcome. We describe the successful long-term post-transplant outcome of a unique case of end-stage respiratory failure due to hereditary PAP-induced pulmonary fibrosis, successfully treated by bilateral lung transplantation and subsequent allogeneic hematopoietic stem cell transplantation. Our report supports treatment with serial lung and hematopoietic stem cell transplantation to improve quality of life and prolong survival, without PAP recurrence, in selected patients with end-stage hereditary PAP

Uncontrolled DCD lungs can survive the donor's death for an afterlife dimension in another body

Science tells us the human body can only survive for a few minutes without oxygen. In her book "Surviving death", the journalist Leslie Kean investigates evidence for an afterlife [1]. In the introduction she stated "While exploring the evidence for an afterlife, I witnessed some unbelievable things that are not supposed to be possible in our material world…… I also studied numerous published papers, including those by medical doctors, describing clinically dead patients with no brain function who reported journeys to a sublime afterlife dimension."status: publishe