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Importance: Median organ waiting times published by transplant organizations may be biased when not appropriately accounting for censoring, death, and competing events. This can lead to overly optimistic waiting times for all transplant programs and, consequently, may deceive patients on the waiting list, transplant physicians, and health care policymakers., Objective: To apply competing-risk multistate models to calculate probabilities for transplantation and adverse outcomes on the Swiss national transplant waiting list., Design, Setting, and Participants: The WAIT (Waitlist Analysis in Transplantation) study was a retrospective cohort study of all transplant candidates in Switzerland listed from January 1, 2018, or later and observed until December 31, 2023. Transplant candidates were listed in 1 of the 6 transplant centers (Basel, Bern, Geneva, Lausanne, St Gallen, and Zurich) for heart, liver, lungs, kidney, or pancreas and/or islet transplant. A total of 4352 candidates were listed during the study period, of whom 709 (16.3%) were excluded due to living-donor transplant (691 in the kidney program and 18 in the liver program)., Exposure: Waiting for organ transplant., Main Outcomes and Measures: Time to transplantation, death, or delisting. Competing-risk multistate models were used to analyze time-to-event data from the national organ waiting list with the Aalen-Johansen estimator to compute probabilities for both transplant and adverse outcomes. Results were compared with the sample median among only those undergoing transplant and the Kaplan-Meier method with censoring of competing events., Results: Data from 3643 transplant candidates (2428 [66.6%] male; median age, 56 [range, 0-79] years) were included in the analysis. The median time to transplantation (MTT) was 0.91 (95% CI, 0.83-1.07) years for heart, 3.10 (95% CI, 2.57-3.77) years for kidney, 1.32 (95% CI, 0.76-1.55) years for liver, 0.80 (95% CI, 0.37-1.12) years for lung, and 1.62 (95% CI, 0.91-2.17) years for pancreas and/or islet programs. Alternative estimation methods introduced bias to varying degrees: the sample median among only persons undergoing transplantation underestimated the waiting time by 38% to 61% and the Kaplan-Meier method by 2% to 12% compared with the MTT., Conclusions and Relevance: In this cohort study of transplant candidates in Switzerland, the MTT, the duration at which the transplant probability is 0.50, was used as a measure of average waiting time. Suboptimal methods led to biased and overly optimistic waiting time estimations; thus, applying appropriate competing-risk methods to address censoring and competing events is crucial.

Modic type 1 changes (MC1) are painful vertebral bone marrow lesions frequently found in patients suffering from chronic low-back pain. Marrow fibrosis is a hallmark of MC1. Bone marrow stromal cells (BMSCs) are key players in other fibrotic bone marrow pathologies, yet their role in MC1 is unknown. The present study aimed to characterise MC1 BMSCs and hypothesised a pro-fibrotic role of BMSCs in MC1. BMSCs were isolated from patients undergoing lumbar spinal fusion from MC1 and adjacent control vertebrae. Frequency of colony-forming unit fibroblast (CFU-F), expression of stem cell surface markers, differentiation capacity, transcriptome, matrix adhesion, cell contractility as well as expression of pro-collagen type I alpha 1, α-smooth muscle actin, integrins and focal adhesion kinase (FAK) were compared. More CFU-F and increased expression of C-X-C-motif-chemokine 12 were found in MC1 BMSCs, possibly indicating overrepresentation of a perisinusoidal BMSC population. RNA sequencing analysis showed enrichment in extracellular matrix proteins and fibrosis-related signalling genes. Increases in pro-collagen type I alpha 1 expression, cell adhesion, cell contractility and phosphorylation of FAK provided further evidence for their pro-fibrotic phenotype. Moreover, a leptin receptor high expressing (LEPRhigh) BMSC population was identified that differentiated under transforming growth factor beta 1 stimulation into myofibroblasts in MC1 but not in control BMSCs. In conclusion, pro-fibrotic changes in MC1 BMSCs and a LEPRhigh MC1 BMSC subpopulation susceptible to myofibroblast differentiation were found. Fibrosis is a hallmark of MC1 and a potential therapeutic target. A causal link between the pro-fibrotic phenotype and clinical characteristics needs to be demonstrated.

Biomaterials with antimicrobial properties are now commonly used in different clinical specialties including orthopedics, endodontic, and traumatology. As a result, assessing the antimicrobial effect of coatings applied on implants is of critical importance. In this study, we demonstrate that isothermal microcalorimetry (IMC) can be used for monitoring bacterial growth and biofilm formation at the surface of such coatings and for determining their antimicrobial effects. The antibacterial effects of silver doped hydroxyapatite (HA) and calcium hydroxide coatings on Staphylococcus epidermidis were determined with a minimal workload. Using the Gompertz growth model we determined biofilm growth rates close to those values reported in the literature. Furthermore, we were able to estimate the reduction in the bacterial inocula originally applied at the surface of the coatings. Therefore, in addition to monitoring the antimicrobial effect of silver doped HA and calcium hydroxide coatings, we also demonstrate that IMC might be a valuable tool for assessing such antimicrobial properties of implant coatings at a minimal workload., (© 2014 Wiley Periodicals, Inc.)