Project description:BackgroundAlthough single and double lung transplantation outcomes for chronic obstructive pulmonary disease (COPD) have been investigated, right and left single lung transplants have never been rigorously compared to evaluate disease-specific differences. Single lung transplants for COPD often have hyperinflation of the contralateral native lung, which may be more pronounced in left lung transplants.MethodsUsing the United Network for Organ Sharing registry, we conducted a retrospective cohort study of 5,585 adults who underwent lung transplantation for COPD from May 4, 2005 to June 30, 2017. Subjects were followed until March 2019. Post-transplant survival was compared using Cox proportional hazards and Royston and Parmar's flexible parametric survival models. We adjusted for donor and recipient factors with known or plausible associations with survival.ResultsLung transplant recipients who received a left single lung transplant for COPD had an increased risk of post-transplant death when compared with those who received a right single lung transplant for COPD (hazard ratio [HR]: 1.24, 95% CI: 1.08-1.48, p = 0.002). Survival did not differ significantly between double lung transplant and right single lung transplant recipients (HR: 0.88, 95% CI: 0.77-1.02, p = 0.086). Adjusted 5-year survival was 57.8% (95% CI: 55.7-60.1) for double lung recipients, 56.7% (95% CI: 55.4-58.0) for right single lung recipients, and 50.9% (95% CI: 47.2-55.0) for left single lung recipients.ConclusionsIn COPD, right single lung transplantation was associated with improved post-transplant survival compared with left single lung transplantation, and no significant difference in post-transplant survival compared with double lung transplantation was found. In light of the ongoing donor lung shortage, preferential allocation of right single lungs to patients with COPD should be considered.
Project description:Conventional orthotopic implantation of left liver grafts is technically demanding and requires consideration of limited space and vascular complications. The study proposed a modified approach termed "left at right" liver transplantation (LAR-LT), wherein left liver grafts were rotated and implanted in right subphrenic spaces. The selection of recipients for this approach is based on the measurement of the right subphrenic space width and left liver graft length, in which a rotated left liver graft could be comfortably placed in the right subphrenic space. A total of 36 recipients who had undergone LAR-LT between July 2006 and December 2017 were retrospectively reviewed. None of recipients died of complications related to this approach immediately after operation. All grafts showed remarkable increment in liver volume and bi-directional regeneration to fit well within the right abdominal cavity. Meanwhile, the alignment of the biliary tree in LAR-LT is quite straight, making no difficulty in both anastomosis during operation and dealing with biliary stenosis afterward. As such, long-term outcome of LAR-LT is satisfactory. Keeping in mind certain technical concerns, a heterotopic LAR-LT might be safely applied as an alternative with an easier reconstruction procedure for select patients.
Project description:Ex vivo lung perfusion (EVLP) has become a reality as a technique to evaluate and recondition lungs from marginal donors. We report the first case on the use of EVLP followed by separate transplantation in two different centres. The local organ procurement organization proposed the lungs of a 53-year-old non-smoker donor who died for cerebral haemorrhage. P/F ratio was 294 after lung recruitment manoeuvres. Oto score was 10. Two centres accepted the grafts for two single transplantations under the condition of EVLP evaluation. After usual retrieval, the bi-pulmonary block was transferred to Centre 1 and EVLP was run as previously described. At the end of the procedure the two lungs were evaluated separately and both judged suitable for transplantation. After cooling and storage on ice, the block was separated on the back table. The left lung was transplanted in a patient with pulmonary fibrosis at Centre 1; surgery was complicated by cardiac arrhythmias that required several defibrillations. The right lung was transferred on ice to Centre 2, 250 km away from Centre 1, and transplanted in a patient with idiopathic pulmonary fibrosis. Thirty months after transplantations Patient 1 and Patient 2 are both alive, in good clinical conditions. This is the first report of the separate use of lungs after EVLP for non-urgent recipients in two different centres. This experience opens the door to a new allocation model with great potentials on organ shortage. Actually, we demonstrated that the perspective of a 'lung repair centre' is feasible and effective.
Project description:According to a theory of magnitude (ATOM, Walsh, 2003, 2015), the cognitive representations of quantity, time, and space share a general magnitude code. Interestingly though, research has largely ignored the relationship between physical (stimulus) size and spatial (response) location. We conducted two experiments investigating compatibility effects between physical stimulus size and left-right responses. In both experiments, right-handed participants responded to a small or a large square stimulus by pressing a left or a right key. In Experiment 1, size was the relevant stimulus feature and we varied the S-R mapping within participants. Results revealed a strong compatibility effect: Performance was better with the compatible mapping (small-left and large-right) than with the incompatible mapping (large-left and small-right). In Experiment 2, participants responded to stimulus color, which varied independently of stimulus size, by pressing a left or right key. Results showed a congruency effect that mirrored the compatibility effect of Experiment 1. The results of our experiments suggest a strong relationship between the cognitive representation of physical (stimulus) size and response location in right-handers. The findings support the notion of a general magnitude code, as proposed in ATOM.
Project description:A 56-year-old woman was referred to the cardiology department of the Shahid Modarres hospital. The patient had a history of pulmonary thromboembolism 20 years ago which had been managed by the inferior vena cava filter and since then the patient has been on warfarin. Her chief complaint was chronic dyspnea on exertion (NYHA class II) from several years ago. Right and left heart catheterization was performed for evaluation of pulmonary artery pressure. We found rich collateral formations between LCX as well as RCA and right pulmonary artery, primarily assumed as multiple fistulas. Among patients who have chronic thromboembolic pulmonary hypertension, systemic collateral supply to the pulmonary parenchyma has been previously reported to occur from both bronchial and/or nonbronchial systemic circulations. Our patient had neither signs of heart failure nor myocardial ischemia and, thus, was a candidate for conservative management. The adenosine pulmonary reactivity test was not performed because of low pulmonary pressure which had been estimated to be high.
Project description:Colorectal cancers (CRCs) exhibit differences in incidence, pathogenesis, molecular pathways, and outcome depending on the location of the tumor. The transcriptomes of 27,927 single human CRC cells from 3 left-sided and 3 right-sided CRC patients were profiled by single-cell RNA-Seq (scRNA-Seq). Right-sided CRC harbors a significant proportion of exhausted CD8+ T cells of a highly migratory nature. One cluster of cells from left-sided CRC exhibiting states preceding exhaustion and a high ratio of preexhausted/exhausted T cells were favorable prognostic markers. Notably, we identified a potentially novel RBP4+NTS+ subpopulation of cancer cells that exclusively expands in left-sided CRC. Tregs from left-sided CRC showed higher levels of immunotherapy-related genes than those from right-sided CRC, indicating that left-sided CRC may have increased responsiveness to immunotherapy. Antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) induced by M2-like macrophages were more pronounced in left-sided CRC and correlated with a good prognosis in CRC.
Project description:Inherent hemispheric asymmetry is significant for cognition, language and other functions. An understanding of normal brain and asymmetry development in the early period will further the knowledge of how different hemispheres prioritize specific functions, which is still unknown. We analysed the developmental changes in and asymmetry of the proteome in the bilateral frontal lobes of three foetal specimens in the late first trimester of pregnancy (9, 11, 13 gestational weeks). We found that during this period, the difference in expression between gestational weeks increased, and the difference in asymmetric expression decreased. The patterns of protein expression changes in the bilateral frontal lobes were different. Our results show that brain asymmetry can be observed in the early stage. Researchers can use these findings to further investigate the mechanisms of brain asymmetry.
Project description:Understanding how left-right (LR) asymmetry is generated in vertebrate embryos is an important problem in developmental biology. In humans, a failure to align the left and right sides of cardiovascular and/or gastrointestinal systems often results in birth defects. Evidence from patients and animal models has implicated cilia in the process of left-right patterning. Here, we review the proposed functions for cilia in establishing LR asymmetry, which include creating transient leftward fluid flows in an embryonic 'left-right organizer'. These flows direct asymmetric activation of a conserved Nodal (TGF?) signalling pathway that guides asymmetric morphogenesis of developing organs. We discuss the leading hypotheses for how cilia-generated asymmetric fluid flows are translated into asymmetric molecular signals. We also discuss emerging mechanisms that control the subcellular positioning of cilia and the cellular architecture of the left-right organizer, both of which are critical for effective cilia function during left-right patterning. Finally, using mosaic cell-labelling and time-lapse imaging in the zebrafish embryo, we provide new evidence that precursor cells maintain their relative positions as they give rise to the ciliated left-right organizer. This suggests the possibility that these cells acquire left-right positional information prior to the appearance of cilia.This article is part of the themed issue 'Provocative questions in left-right asymmetry'.