ABSTRACT
BACKGROUND: Multi-visceral organ transplant is uncommon. As a result of the rarity of these surgeries, there are limited studies, making it difficult to interpret outcomes and identify specific patient complications. We aim to assess the indications for multi-organ transplant, the time on the wait-list and evaluate outcomes including patient survival, graft survival and postoperative complications in an Australian context. METHODS: Patients undergoing multi-organ transplant from 1993 to 2018 at The Prince Charles Hospital, Brisbane, Australia were retrospectively reviewed, looking at baseline characteristics and post-transplant morbidity, mortality and graft survival. RESULTS: A total of 37 patients were included in the study, comprising 22 heart-lung transplants, eight heart-kidney transplants and seven heart-lung-liver transplants. There were six domino heart transplants performed, all in the heart-lung-liver transplant group. The mean age at transplant was 37 years and the mean wait-list time was 10 months. One patient, receiving a heart-lung transplant, required re-transplantation (bilateral lung) at 3 years. One-year (1-year) survival was 91% for heart-lung transplants, 86% for heart-lung-liver transplants and 87.5% for heart-kidney transplants. Five- and ten-year (5- and 10-year) survival was 79% for both in heart-lung transplant, 43% and 29% for heart-lung-liver transplant and 87.5% for both in heart-kidney transplant. CONCLUSION: Patients undergoing multi-organ transplant at our unit had long-term survival and organ function comparable to international data. In addition, waitlist time for multi-organ transplant was not found to be excessive.
Subject(s)
Hospitals/statistics & numerical data , Organ Transplantation/statistics & numerical data , Postoperative Complications/epidemiology , Registries , Tissue Donors , Tissue and Organ Procurement/methods , Adolescent , Adult , Australia , Female , Graft Survival , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities.
Subject(s)
Analgesics/administration & dosage , Bone Diseases/physiopathology , Chronic Pain/physiopathology , Analgesics/pharmacology , Analgesics, Opioid/administration & dosage , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Bone Diseases/drug therapy , Bone and Bones/innervation , Bone and Bones/physiopathology , Chronic Pain/drug therapy , Chronic Pain/etiology , Humans , Knee Joint/metabolismABSTRACT
Glucose is an important stimulus for glucagon-like peptide 1 (GLP-1) secretion, but the mechanisms of secretion have not been investigated in integrated physiological models. We studied glucose-stimulated GLP-1 secretion from isolated perfused rat small intestine. Luminal glucose (5% and 20% w/v) stimulated the secretion dose dependently, but vascular glucose was without significant effect at 5, 10, 15, and 25 mmol/L. GLP-1 stimulation by luminal glucose (20%) secretion was blocked by the voltage-gated Ca channel inhibitor, nifedipine, or by hyperpolarization with diazoxide. Luminal administration (20%) of the nonmetabolizable sodium-glucose transporter 1 (SGLT1) substrate, methyl-α-D-glucopyranoside (α-MGP), stimulated release, whereas the SGLT1 inhibitor phloridzin (luminally) abolished responses to α-MGP and glucose. Furthermore, in the absence of luminal NaCl, luminal glucose (20%) did not stimulate a response. Luminal glucose-stimulated GLP-1 secretion was also sensitive to luminal GLUT2 inhibition (phloretin), but in contrast to SGLT1 inhibition, phloretin did not eliminate the response, and luminal glucose (20%) stimulated larger GLP-1 responses than luminal α-MGP in matched concentrations. Glucose transported by GLUT2 may act after metabolization, closing KATP channels similar to sulfonylureas, which also stimulated secretion. Our data indicate that SGLT1 activity is the driving force for glucose-stimulated GLP-1 secretion and that KATP-channel closure is required to stimulate a full-blown glucose-induced response.
