- Islet-Immune Interactions in Type 1 Diabetes: The Nexus of Beta Cell Destruction. [Review]
- CEClin Exp Immunol 2019 Jul 15
- Recent studies in Type 1 Diabetes (T1D) support an emerging model of disease pathogenesis that involves intrinsic β-cell fragility combined with defects in both innate and adaptive immune cell regula…
Recent studies in Type 1 Diabetes (T1D) support an emerging model of disease pathogenesis that involves intrinsic β-cell fragility combined with defects in both innate and adaptive immune cell regulation. This combination of defects induces systematic changes leading to organ-level atrophy and dysfunction of both the endocrine and exocrine portions of the pancreas, ultimately culminating in insulin deficiency and β-cell destruction. In this review, we discuss the animal model data and human tissue studies that have informed our current understanding of the cross-talk that occurs between β-cells, the resident stroma, and immune cells that potentiate T1D. Specifically, we will review the cellular and molecular signatures emerging from studies on tissues derived from organ procurement programs, focusing on in situ defects occurring within the T1D islet microenvironment, many of which are not yet detectable by standard peripheral blood biomarkers. In addition to improved access to organ donor tissues, various methodological advances, including immune receptor repertoire sequencing and single-cell molecular profiling, are poised to improve our understanding of antigen-specific autoimmunity during disease development. Collectively, the knowledge gains from these studies at the islet-immune interface are enhancing our understanding of T1D heterogeneity, likely to be an essential component for instructing future efforts to develop targeted interventions to restore immune tolerance and preserve β-cell mass and function. This article is protected by copyright. All rights reserved.
- The systemic activin response to pancreatic cancer: implications for effective cancer cachexia therapy. [Journal Article]
- JCJ Cachexia Sarcopenia Muscle 2019 Jul 08
- CONCLUSIONS: Pancreatic adenocarcinoma tumours are a source of activin and elicit a systemic activin response in hosts. Human tumours express activins and related factors, while mortality correlates with tumour activin A expression. PDAC tumours also choreograph a systemic activin response that induces organ-specific and gene-specific expression of activin isoforms and muscle wasting. Systemic blockade of activin signalling could preserve muscle and prolong survival, while skeletal muscle-specific activin blockade was only protective for weight loss. Our findings suggest the potential and need for gene-specific and organ-specific interventions. Finally, development of more effective cancer cachexia therapy might require identifying agents that effectively and/or selectively inhibit autocrine vs. paracrine activin signalling.
- Intestinal Preservation Injury: A Comparison Between Rat, Porcine and Human Intestines. [Journal Article]
- IJInt J Mol Sci 2019 Jun 27; 20(13)
- Advanced preservation injury (PI) after intestinal transplantation has deleterious short- and long-term effects and constitutes a major research topic. Logistics and costs favor rodent studies, where…
Advanced preservation injury (PI) after intestinal transplantation has deleterious short- and long-term effects and constitutes a major research topic. Logistics and costs favor rodent studies, whereas clinical translation mandates studies in larger animals or using human material. Despite diverging reports, no direct comparison between the development of intestinal PI in rats, pigs, and humans is available. We compared the development of PI in rat, porcine, and human intestines. Intestinal procurement and cold storage (CS) using histidine-tryptophan-ketoglutarate solution was performed in rats, pigs, and humans. Tissue samples were obtained after 8, 14, and 24 h of CS), and PI was assessed morphologically and at the molecular level (cleaved caspase-3, zonula occludens, claudin-3 and 4, tricellulin, occludin, cytokeratin-8) using immunohistochemistry and Western blot. Intestinal PI developed slower in pigs compared to rats and humans. Tissue injury and apoptosis were significantly higher in rats. Tight junction proteins showed quantitative and qualitative changes differing between species. Significant interspecies differences exist between rats, pigs, and humans regarding intestinal PI progression at tissue and molecular levels. These differences should be taken into account both with regards to study design and the interpretation of findings when relating them to the clinical setting.
- Successful preservation and transplant of warm ischaemic lungs from controlled donors after circulatory death by prolonged in situ ventilation during normothermic regional perfusion of abdominal organs. [Journal Article]
- ICInteract Cardiovasc Thorac Surg 2019 Jun 26
- CONCLUSIONS: Our approach resulted in adequate lung preservation and successful transplants without detrimental effects on abdominal organ procurement, confirming the possibility of overcoming the obstacle of a long no-touch period in a DCD setting.
- Intraoperative management of brain-dead organ donors by anesthesiologists during an organ procurement procedure: results from a French survey. [Journal Article]
- BABMC Anesthesiol 2019 Jun 15; 19(1):108
- CONCLUSIONS: Declared anesthetic practice appeared in accordance with guidelines concerning organ donor management in the ICU. Further studies are needed to evaluate the specific impact of intraoperative management during this procedure and thus the need for specific anesthetic guidelines.
- The Kidney-Transplant Waiting List and the Opioid Crisis. [Letter]
- NEJMN Engl J Med 2019 06 06; 380(23):2273-2274
- Pretransplant Biopsy of Marginal Kidneys: Is It Necessary? [Journal Article]
- TPTransplant Proc 2019; 51(5):1585-1589
- CONCLUSIONS: Selection of kidneys based on histological findings may not influence the graft survival and implies a higher cold ischemia time. More data are necessary to provide insight into which clinical, histologic, and biochemical parameters are necessary for decision making on kidney acceptance.
- Attitudes of Iranian students about organ donation: a qualitative study. [Journal Article]
- BMBMC Med Ethics 2019 May 28; 20(1):36
- CONCLUSIONS: Many factors influence the students' attitudes toward organ donation. Identification and explanation of these factors can help healthcare managers and policymakers for planning and improving the organ donation culture in the society.
- Pulmonary arteriopexy to prevent pulmonary artery kinking in orthotopic heart transplantation. [Journal Article]
- JCJ Card Surg 2019; 34(7):617-619
- Heart transplantation is still the best treatment for patients with end-stage heart failure unresponsive to medical therapy or those treated with mechanical circulatory support. The surgical techniqu…
Heart transplantation is still the best treatment for patients with end-stage heart failure unresponsive to medical therapy or those treated with mechanical circulatory support. The surgical technique for heart transplantation is fraught with potential complications. One of these potential complications, kinking of the pulmonary artery after anastomosis of the recipient and donor pulmonary arteries, has been reported as a cause of acute right ventricular failure. We describe a technique to ensure proper configuration of the pulmonary artery after heart transplantation via a pulmonary arteriopexy to restore a physiologically appropriate angle of the great vessels.
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- Measures influencing post-mortem organ donation rates in Germany, the Netherlands, Spain and the UK : A systematic review. [Journal Article]
- AAnaesthesist 2019; 68(6):377-383
- CONCLUSIONS: Donation after cardiac death (DCD), expanded donor criteria, increasing public awareness and introduction of an organ donor register should be discussed as measures to increase organ donation rates in Germany.