Revising model for end-stage liver disease from calendar-time cross-sections with correction for selection bias.

BACKGROUND: Eurotransplant liver transplant candidates are prioritized by Model for End-stage Liver Disease (MELD), a 90-day waitlist survival risk score based on the INR, creatinine and bilirubin. Several studies revised the original MELD score, UNOS-MELD, with transplant candidate data by modelling 90-day waitlist mortality from waitlist registration, censoring patients at delisting or transplantation. This approach ignores biomarkers reported after registration, and ignores informative censoring by transplantation and delisting. METHODS: We study how MELD revision is affected by revision from calendar-time cross-sections and correction for informative censoring with inverse probability censoring weighting (IPCW). For this, we revised UNOS-MELD on patients with chronic liver cirrhosis on the Eurotransplant waitlist between 2007 and 2019 (n = 13,274) with Cox models with as endpoints 90-day survival (a) from registration and (b) from weekly drawn calendar-time cross-sections. We refer to the revised score from cross-section with IPCW as DynReMELD, and compare DynReMELD to UNOS-MELD and ReMELD, a prior revision of UNOS-MELD for Eurotransplant, in geographical validation. RESULTS: Revising MELD from calendar-time cross-sections leads to significantly different MELD coefficients. IPCW increases estimates of absolute 90-day waitlist mortality risks by approximately 10 percentage points. DynReMELD has improved discrimination over UNOS-MELD (delta c-index: 0.0040, p < 0.001) and ReMELD (delta c-index: 0.0015, p < 0.01), with differences comparable in magnitude to the addition of an extra biomarker to MELD (delta c-index: ± 0.0030). CONCLUSION: Correcting for selection bias by transplantation/delisting does not improve discrimination of revised MELD scores, but substantially increases estimated absolute 90-day mortality risks. Revision from cross-section uses waitlist data more efficiently, and improves discrimination compared to revision of MELD exclusively based on information available at listing.

Immediate impact of COVID-19 on transplant activity in the Netherlands.

The rapid emergence of the COVID-19 pandemic is unprecedented and poses an unparalleled obstacle in the sixty-five year history of organ transplantation. Worldwide, the delivery of transplant care is severely challenged by matters concerning - but not limited to - organ procurement, risk of SARS-CoV-2 transmission, screening strategies of donors and recipients, decisions to postpone or proceed with transplantation, the attributable risk of immunosuppression for COVID-19 and entrenched health care resources and capacity. The transplant community is faced with choosing a lesser of two evils: initiating immunosuppression and potentially accepting detrimental outcome when transplant recipients develop COVID-19 versus postponing transplantation and accepting associated waitlist mortality. Notably, prioritization of health care services for COVID-19 care raises concerns about allocation of resources to deliver care for transplant patients who might otherwise have excellent 1-year and 10-year survival rates. Children and young adults with end-stage organ disease in particular seem more disadvantaged by withholding transplantation because of capacity issues than from medical consequences of SARS-CoV-2. This report details the nationwide response of the Dutch transplant community to these issues and the immediate consequences for transplant activity. Worrisome, there was a significant decrease in organ donation numbers affecting all organ transplant services. In addition, there was a detrimental effect on transplantation numbers in children with end-organ failure. Ongoing efforts focus on mitigation of not only primary but also secondary harm of the pandemic and to find right definitions and momentum to restore the transplant programs.

Blood sample stability at room temperature for counting red and white blood cells and platelets.

Blood handling required for different cellular variables is different. In a practical setting of blood sampling approximately 4 h separated from the first analysis, we compared the analysis of blood cell variables at this 4-h point with analysis of blood stored for approximately 48 h (over the weekend) at room temperature. Blood was collected from 304 apparently healthy individuals aged between 17 and 70 years, with a female/male ratio of 1.8, in K3EDTA. Measurement was performed with a Beckman Coulter Counter Maxm. In addition to the comparison of the data and their correlation on the two time points, we investigated agreement between the data using analysis according to Bland and Altman. Counts of white and red blood cells and platelets were found stable over time and agreement of data was excellent. Platelet mean volume increased as expected between the two time points from 8.8 to 10.3 fl. The white blood cell subpopulations, however, changed over time with a decrease in neutrophils and monocytes and increases in lymphocytes and eosinophils. Apparently, ageing of the sample resulted in the alteration of certain cell characteristics leading to a change in automated cell classification without changing the total number of cells. Among the preanalytical variables recorded, only the time of the year and gender were found to be minor determinants (r < .25) of some of the differences between approximately 4 and approximately 48 h analysis delay. It is concluded that after storage at room temperature over approximately 48 h counts of red, total white cells, platelets and analysis of platelet volume can be combined in one assay session.