National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States.

BACKGROUND: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. METHODS: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. RESULTS: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. CONCLUSION: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety.

Public discourse and policy change: Absence of harm from increased oversight and transparency in OPO performance.

The Centers for Medicare and Medicaid Services announced changes to the Final Rule for organ procurement organizations (OPOs) in November 2020, after a 23-month period of public debate. One concern among transplant stakeholders was that public focus on OPO underperformance would harm deceased donation. Using CDC-WONDER data, we studied whether donation performance dropped during the era of public debate about OPO reform (December 2018-February 2020). Overall OPO performance as measured relative to cause, age, and location-consistent deaths rose by 12.3% in 2019, compared to a median annual change of 2.5% 2009-2019. Organ recoveries exceeded seasonally adjusted forecasts by 4.2% in the first half of 2019, by 8.1% following the Executive Order issuing a mandate for OPO metric reform, and by 14.1% between the Notice of Public Rule Making and the onset of COVID-19-related systemic disruptions. We describe changes in donor phenotype in the period of increased performance; improvement was greatest for older and donation after cardiac death (DCD) donors, and among decedents who did not have a drug-related mechanism of death. In summary, performance during an era of intense public debate and proposed regulatory changes yielded 692 additional donors over expectations, and no detriment to organ donation was observed.

Surface Engineering of Auxetic Scaffolds for Neural and Vascular Differentiation from Human Pluripotent Stem Cells.

Auxetic materials are the materials that can display negative Poisson's ratio that describes the degree to which a material contracts (or expands) transversally when axially strained. Human stem cells sense the mechanical properties of the microenvironment, including material surface properties, stiffness, and Poisson's ratio. In this study, six different auxetic polyurethane (PU) foams with different elastic modulus (0.7-1.8 kPa) and Poisson's ratio (-0.1 to -0.5) are used to investigate lineage specification of human induced pluripotent stem cells (hiPSCs). The surfaces of the foams are modified with chitosan or heparin to enhance the adhesion and proliferation of hiPSCs. Then, the vascular and neural differentiation of hiPSCs are investigated on different foams with distinct elastic modulus and Poisson's ratio. With different auxetic foams, cells show differential adherent density and differentiation capacity. Chitosan and heparin surface functionalization promote the hindbrain and hippocampal markers, but not forebrain markers during neural patterning of hiPSCs. Properly surface engineered auxetic scaffolds can also promote vascular differentiation of hiPSCs. This study represents a versatile and multifunctional scaffold fabrication approach and can lead to a suitable system for establishing hiPSC culture models in applications of neurovascular disease modeling and drug screening.

Digital Twin Modeling of Flexible Perovskite Nano-Films with In-Situ Mechanical Microscopy Validation.

Flexible perovskite solar cells introduce opportunities for high throughput, high specific weight, and short energy payback time photovoltaics. However, they require additional investigation into their mechanical resiliency. This work investigates the mechanical properties and behaviors of perovskite thin films and builds a robust model for future research. A two-pronged approach was utilized. Perovskite thin films were flexed in a three-point bend mode with in-situ SEM. Novel insights into the perovskite mechanical behaviors with varying substrate layers were gained. Modeling and validation, the second prong, was completed with finite element analysis. Model coupons of the imaged perovskite architectures were built, with sensitivity analysis completed to provide mechanical property estimates. The results demonstrate that mechanical degradation of perovskite thin films on polyethylene terephthalate (PET) primarily presents as a crack in the grain boundaries between crystals. Perovskite thin films on Indium Tin Oxide (ITO) and PET primarily crack in a periodic pattern regardless of the placement of perovskite crystals.

Design, Fabrication, Structure Optimization and Pressure Sensing Demonstration of COC Piezoelectret Sensor and Sensor Array.

This study reported on the design and fabrication of a pseudo-piezoelectric material (piezoelectret) from cyclic olefin copolymer (COC) based on a micropillar structure. The fabrication feasibility of such structure was explored and piezoelectret with the good piezoelectric activity (characterized by quasi-static piezoelectric coefficient d33) was demonstrated. Response surface method with a central composite design was employed to investigate the effects of the structure parameter on the piezoelectric coefficient d33. An optimal structure design was obtained and was validated by experiments. With the optimal design, d33 can reach an exceptional high value of ~9000 pC/N under low pressure. The charging process and the electrical and electromechanical characteristics were further investigated by experimentation and modeling. We further demonstrated the scalability of the fabrication process and demonstrated the application of these sensors in position specific pressure sensing (pressure mapping).

Procurement of Pancreatic Tissue for Research From Deceased Donors Before vs After the CMS Final Rule in 2020.

This cohort study examines changes in research pancreas procurement from deceased donors before and after the Centers for Medicare & Medicaid Services (CMS) updated its Final Rule in November 2020.