Evolving Impact of COVID-19 on Transplant Center Practices and Policies in the United States

In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID-19 on transplant recipients and center-level practices. We therefore conducted a six-week follow-up survey May 7-15, 2020, and linked responses to the COVID-19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID-19–positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS-CoV-2. Our findings demonstrate persistent heterogeneity in center-level response to COVID-19 even as transplant activity resumes, making ongoing national data collection and real-time analysis critical to inform best practices.     

A novel immune competent murine hypertrophic scar contracture model: A tool to elucidate disease mechanism and develop new therapies

Hypertrophic scar (HSc) contraction following burn injury causes contractures. Contractures are painful and disfiguring. Current therapies are marginally effective. To study pathogenesis and develop new therapies, a murine model is needed. We have created a validated immune‐competent murine HSc model. A third‐degree burn was created on dorsum of C57BL/6 mice. Three days postburn, tissue was excised and grafted with ear skin. Graft contraction was analyzed and tissue harvested on different time points. Outcomes were compared with human condition to validate the model. To confirm graft survival, green fluorescent protein (GFP) mice were used, and histologic analysis was performed to differentiate between ear and back skin. Role of panniculus carnosus in contraction was analyzed. Cellularity was assessed with 4′,6‐diamidino‐2‐phenylindole. Collagen maturation was assessed with Picro‐sirius red. Mast cells were stained with Toluidine blue. Macrophages were detected with F4/80 immune. Vascularity was assessed with CD31 immune. RNA for contractile proteins was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). Elastic moduli of skin and scar tissue were analyzed using a microstrain analyzer. Grafts contracted to ～45% of their original size by day 14 and maintained their size. Grafting of GFP mouse skin onto wild‐type mice, and analysis of dermal thickness and hair follicle density, confirmed graft survival. Interestingly, hair follicles disappeared after grafting and regenerated in ear skin configuration by day 30. Radiological analysis revealed that panniculus carnosus doesn't contribute to contraction. Microscopic analyses showed that grafts show increase in cellularity. Granulation tissue formed after day 3. Collagen analysis revealed increases in collagen maturation over time. CD31 stain revealed increased vascularity. Macrophages and mast cells were increased. qRT‐PCR showed up‐regulation of transforming growth factor beta, alpha smooth muscle actin, and rho‐associated protein kinase 2 in HSc. Tensile testing revealed that human skin and scar tissues are tougher than mouse skin and scar tissues.     

Metacognitive mastery moderates the relationship of alexithymia with cluster C personality disorder traits in adults with substance use disorders

Cluster C personality disorder traits have been observed in substance use disorders and linked with poorer outcome. One potential factor which may cause these disturbances in personality function is alexithymia, or the inability to name and express emotion. There may be other proximate factors which moderate the impact of alexithymia on the expression of cluster C traits, such as metacognitive mastery, which is the ability to use knowledge about mental states of self and others to cope with distress and solve social problems. To examine the possibility that mastery mediated the effects of alexithymia on cluster C traits, we assessed each of these constructs using the Metacognitive Assessment Scale Abbreviated, Toronto Alexithymia Scale and SCID II among 58 adults in an early phase of recovery from substance misuse disorders in a residential setting. Results of a multiple regression revealed that, after controlling for symptom severity and severity of substance misuse history, metacognitive mastery moderated the effect of alexithymia on number of cluster C traits. A median split and subsequent ANCOVA revealed that participants with higher levels of alexithymia and poorer metacognitive mastery had more cluster C traits than the other groups. These findings may have clinical implications, suggesting that patients with substance use disorders may benefit from treatment which addresses metacognitive mastery.     

Bayesian Approach to Estimate AUC,Partition Coefficient and Drug Targeting Index for Studies with Serial Sacrifice Design

Purpose

The current study presents a Bayesian approach to non-compartmental analysis (NCA), which provides the accurate and precise estimate of AUC ₀ ^∞ and any AUC ₀ ^∞ -based NCA parameter or derivation.

Methods

In order to assess the performance of the proposed method, 1,000 simulated datasets were generated in different scenarios. A Bayesian method was used to estimate the tissue and plasma AUC ₀ ^∞ s and the tissue-to-plasma AUC ₀ ^∞ ratio. The posterior medians and the coverage of 95% credible intervals for the true parameter values were examined. The method was applied to laboratory data from a mice brain distribution study with serial sacrifice design for illustration.

Results

Bayesian NCA approach is accurate and precise in point estimation of the AUC ₀ ^∞ and the partition coefficient under a serial sacrifice design. It also provides a consistently good variance estimate, even considering the variability of the data and the physiological structure of the pharmacokinetic model. The application in the case study obtained a physiologically reasonable posterior distribution of AUC, with a posterior median close to the value estimated by classic Bailer-type methods.

Conclusions

This Bayesian NCA approach for sparse data analysis provides statistical inference on the variability of AUC ₀ ^∞ -based parameters such as partition coefficient and drug targeting index, so that the comparison of these parameters following destructive sampling becomes statistically feasible.