Kazunari Tanabe

With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low-level evidence. The number of prospective randomized trials for the treatment of AMR is small, and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated. At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes, and outcomes were discussed. The evidence for different treatments was reviewed, and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented. While it was agreed that the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody, there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.

BACKGROUND: Preliminary data suggest that COVID-19 has reduced access to solid organ transplantation. However, the global consequences of the COVID-19 pandemic on transplantation rates and the effect on waitlisted patients have not been reported. We aimed to assess the effect of the COVID-19 pandemic on transplantation and investigate if the pandemic was associated with heterogeneous adaptation in terms of organ transplantation, with ensuing consequences for waitlisted patients. METHODS: In this population-based, observational, before-and-after study, we collected and validated nationwide cohorts of consecutive kidney, liver, lung, and heart transplants from 22 countries. Data were collected from Jan 1 to Dec 31, 2020, along with data from the same period in 2019. The analysis was done from the onset of the 100th cumulative COVID-19 case through to Dec 31, 2020. We assessed the effect of the pandemic on the worldwide organ transplantation rate and the disparity in transplant numbers within each country. We estimated the number of waitlisted patient life-years lost due to the negative effects of the pandemic. The study is registered with ClinicalTrials.gov, NCT04416256. FINDINGS: Transplant activity in all countries studied showed an overall decrease during the pandemic. Kidney transplantation was the most affected, followed by lung, liver, and heart. We identified three organ transplant rate patterns, as follows: countries with a sharp decrease in transplantation rate with a low COVID-19-related death rate; countries with a moderate decrease in transplantation rate with a moderate COVID-19-related death rate; and countries with a slight decrease in transplantation rate despite a high COVID-19-related death rate. Temporal trends revealed a marked worldwide reduction in transplant activity during the first 3 months of the pandemic, with losses stabilising after June, 2020, but decreasing again from October to December, 2020. The overall reduction in transplants during the observation time period translated to 48 239 waitlisted patient life-years lost. INTERPRETATION: We quantified the impact of the COVID-19 pandemic on worldwide organ transplantation activity and revealed heterogeneous adaptation in terms of organ transplantation, both at national levels and within countries, with detrimental consequences for waitlisted patients. Understanding how different countries and health-care systems responded to COVID-19-related challenges could facilitate improved pandemic preparedness, notably, how to safely maintain transplant programmes, both with immediate and non-immediate life-saving potential, to prevent loss of patient life-years. FUNDING: French national research agency (INSERM) ATIP Avenir and Fondation Bettencourt Schueller.

PURPOSE: We determined the impact of the extent of regional lymphadenectomy on survival in patients with urothelial carcinoma of the upper urinary tract. MATERIALS AND METHODS: Between January 1989 and January 2006, 169 patients with nonmetastatic urothelial carcinoma of the upper urinary tract underwent curative surgery. We previously reported the primary sites of nodal metastases in urothelial carcinoma of the upper urinary tract. Nodal sites where the incidence of metastases was 30% or more were considered regional lymph nodes. When all primary sites were resected, this was considered complete lymphadenectomy. Regional lymphadenectomy without the removal of all primary sites was considered incomplete lymphadenectomy. We retrospectively analyzed the influence of the extent of lymphadenectomy on patient survival. RESULTS: A total of 45 patients (26.6%) underwent complete lymphadenectomy. Lymphadenectomy was performed in an additional 36 patients (21.3%) but it was incomplete. Lymphadenectomy was not performed in 88 patients. Cancer specific survival did not significantly differ between the groups when all patients were analyzed. However, patient survival significantly depended on the extent of lymphadenectomy when we focused on patients with T stage pT3 or higher. Patient survival was likely to improve when the number of lymph nodes removed increased. Multivariate analysis showed that complete lymphadenectomy was a significant prognostic factor for cancer specific survival (p = 0.009) as well as T stage (pT3 or less p = 0.0004) and tumor grade (G3 p = 0.0001). CONCLUSIONS: Although further investigation is required to make a definite conclusion, the extent of lymphadenectomy may significantly influence its therapeutic effect, especially for patients with advanced disease.