Pragmatic strategies to address health disparities along the continuum of care in chronic liver disease.

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.

Hereditary thrombotic thrombocytopenic purpura acquired through liver transplantation: A case report.

A 62-year-old received orthotopic liver transplantation. Three weeks later, thrombotic microangiopathy developed. Testing revealed thrombotic thrombocytopenic purpura (TTP) characterized by low ADAMTS13 (A Disintegrin-like Metallopeptidase with ThromboSpondin type 1 motif 13) activity and no inhibitor of ADAMTS13 protein. Retrospective attainment of donor records revealed a TTP diagnosis, presumably hereditary TTP (hTTP), as an ADAMTS13 protein inhibitor was not mentioned. As the grafted liver does not produce ADAMTS13 protein, the recipient now functionally has hTTP and will likely need plasma transfusions indefinitely. While hTTP is extremely rare, it should be considered a contraindication to liver donation outside of exceptional circumstances. If a potential liver donor has TTP listed on medical history, attempts should be made to determine whether it is autoimmune or hereditary. An accurate medical history is critical as it is the only reliable way to identify hTTP, as outside of acute exacerbations of TTP, donors with hTTP can have normal laboratory values, including normal hemoglobin, platelets, and renal function.

"Can i donate a kidney?" Common questions and simplified answers to the prospective kidney donor.

For individuals with end stage kidney disease (ESKD), kidney transplantation is associated with reduced morbidity, mortality, and decreased health care costs. African Americans have higher rates of end stage kidney disease (ESKD) and reduced access to transplantation compared to their White counterparts. One way to improve access to transplantation is by increasing the number of living donors. Currently, African Americans with ESKD comprise 31% of the transplant waitlist and only 8% of the living kidney donors. Often individuals with ESKD are hesitant to inform loved ones about living donation out of concerns that their donors may feel pressured or may be harmed by donation. Even when patients discuss donation with loved ones, these potential donors may not seek information from their physicians. As an important first step, we provide general information about living donation to primary care physicians for their African Americans patients with ESKD and potential African American donors.

Telemedicine and Health Disparities.

Content available: Author Audio Recording.

Gender and racial disparities in the transplant surgery workforce.

PURPOSE OF REVIEW: This review explores trends in the United States (US) transplant surgery workforce with a focus on historical demographics, post-fellowship job market, and quality of life reported by transplant surgeons. Ongoing efforts to improve women and racial/ethnic minority representation in transplant surgery are highlighted. Future directions to create a transplant workforce that reflects the diversity of the US population are discussed. RECENT FINDINGS: Representation of women and racial and ethnic minorities among transplant surgeons is minimal. Although recent data shows an improvement in the number of Black transplant surgeons from 2% to 5.5% and an increase in women to 12%, the White to Non-White transplant workforce ratio has increased 35% from 2000 to 2013. Transplant surgeons report an average of 4.3 call nights per week and less than five leisure days a month. Transplant ranks 1st among surgical sub-specialties in the prevalence of three well-studied facets of burnout. Concerns about lifestyle may contribute to the decreasing demand for advanced training in abdominal transplantation by US graduates. SUMMARY: Minimal improvements have been made in transplant surgery workforce diversity. Sustained and intentional recruitment and promotion efforts are needed to improve the representation of women and minority physicians and advanced practice providers in the field.

Black Patients With Cirrhosis Have Higher Mortality and Lower Transplant Rates: Results From a Metropolitan Cohort Study.

BACKGROUND AND AIMS: Estimates of racial disparity in cirrhosis have been limited by lack of large-scale, longitudinal data, which track patients from diagnosis to death and/or transplant. APPROACH AND RESULTS: We analyzed a large, metropolitan, population-based electronic health record data set from seven large health systems linked to the state death registry and the national transplant database. Multivariate competing risk analyses, adjusted for sex, age, insurance status, Elixhauser score, etiology of cirrhosis, HCC, portal hypertensive complication, and Model for End-Stage Liver Disease-Sodium (MELD-Na), examined the relationship between race, transplant, and cause of death as defined by blinded death certificate review. During the study period, 11,277 patients met inclusion criteria, of whom 2,498 (22.2%) identified as Black. Compared to White patients, Black patients had similar age, sex, MELD-Na, and proportion of alcohol-associated liver disease, but higher comorbidity burden, lower rates of private insurance, and lower rates of portal hypertensive complications. Compared to White patients, Black patients had the highest rate all-cause mortality and non-liver-related death and were less likely to be listed or transplanted (P < 0.001 for all). In multivariate competing risk analysis, Black patients had a 26% increased hazard of liver-related death (subdistribution HR, 1.26; 95% CI, [1.15-1.38]; P < 0.001). CONCLUSIONS: Black patients with cirrhosis have discordant outcomes. Further research is needed to determine how to address these real disparities in the field of hepatology.

Dismantling structural racism as a root cause of racial disparities in COVID-19 and transplantation.

As the United States faces unparalleled challenges due to COVID-19, racial disparities in health and healthcare have once again taken center stage. If effective interventions to address racial disparities in transplantation, including those magnified by COVID-19, are to be designed and implemented at the national level, it is first critical to understand the complex mechanisms by which structural, institutional, interpersonal, and internalized racism influence the presence of racial disparities in healthcare and transplantation. Specifically, we must deeply re-evaluate how scientists and clinicians think about race in the transplant context, and we must actively shift our efforts from merely observing disparities to acknowledging and acting on racism as a root cause underlying the vast majority of these disparities. We must do better to ensure equitable access and outcomes for all transplant patients, including within the current COVID-19 pandemic. We respectfully offer this viewpoint as a call to action to every reader to join us in working together to help dismantle racist influences and advance transplant equity.

Mechanostructural adaptations preceding postpneumonectomy lung growth.

In many species, pneumonectomy results in compensatory growth in the remaining lung. Although the late mechanical consequences of murine pneumonectomy are known, little is known about the anatomic adaptations and respiratory mechanics during compensatory lung growth. To investigate the structural and mechanical changes during compensatory growth, mice were studied for 21 days after left pneumonectomy using microCT and respiratory system impedance (FlexiVent). Anatomic changes after left pneumonectomy included minimal mediastinal shift or chestwall remodeling, but significant displacement of the heart and cardiac lobe. Mean displacement of the cardiac lobe centroid was 5.2 ± 0.8 mm. Lung impedance measurements were used to investigate the associated changes in respiratory mechanics. Quasi-static pressure-volume loops demonstrated progressive increase in volumes with decreased distensibility. Measures of quasi-static compliance and elastance were increased at all time points postpneumonectomy (P < .01). Oscillatory mechanics demonstrated a significant change in tissue impedance on the third day after pneumonectomy. The input impedance on day 3 after pneumonectomy demonstrated a significant increase in tissue damping (5.8 versus 4.3 cm H(2)O/mL) and elastance (36.7 versus 26.6 cm H(2)O/mL) when compared to controls. At all points, hysteresivity was unchanged (0.17). We conclude that the timing and duration of the mechanical changes was consistent with a mechanical signal for compensatory growth.

Cross-circulation and cell distribution kinetics in parabiotic mice.

Blood-borne nucleated cells participate not only in inflammation, but in tissue repair and regeneration. Because progenitor and stem cell populations have a low concentration in the blood, the circulation kinetics and tissue distribution of these cells is largely unknown. An important approach to tracking cell lineage is the use of fluorescent tracers and parabiotic models of cross-circulation. Here, we investigated the cross-circulation and cell distribution kinetics of C57/B6 GFP(+)/wild-type parabionts. Flow cytometry analysis of the peripheral blood after parabiosis demonstrated no evidence for a "parabiotic barrier" based on cell size or surface characterstics; all peripheral blood cell subpopulations in this study reached equilibrium within 14 days. Whole blood fluorescence analysis indicated that the mean exchange flow rate was 16 µl/h or 0.66% of the circulating blood volume per hour. Studies of peripheral lymphoid organs indicated differential cell distribution kinetics. Some subpopulations, such as CD8(+) and CD11c(+), equilibrated in both lymph nodes and spleen indicating a residence time <28 days; in contrast, other lymphocyte subpopulations, such as B220(+) and CD4(+) cells, had not yet reached equilibrium at 28 days. We conclude that parabiosis can provide important insights into defining tissue distribution, residence times, and recirculating pools using fluorochrome markers of cell lineage.

CD34+ progenitor to endothelial cell transition in post-pneumonectomy angiogenesis.

In many species, pneumonectomy triggers compensatory lung growth that results in an increase not only in lung volume, but also in alveolar number. Whether the associated alveolar angiogenesis involves the contribution of blood-borne progenitor cells is unknown. To identify and characterize blood-borne progenitor cells contributing to lung growth after pneumonectomy in mice, we studied wild-type and wild-type/green fluorescence protein (GFP) parabiotic mice after left pneumonectomy. Within 21 days of pneumonectomy, a 3.2-fold increase occurred in the number of lung endothelial cells. This increase in total endothelial cells was temporally associated with a 7.3-fold increase in the number of CD34(+) endothelial cells. Seventeen percent of the CD34(+) endothelial cells were actively proliferating, compared with only 4.2% of CD34(-) endothelial cells. Using wild-type/GFP parabiotic mice, we demonstrated that 73.4% of CD34(+) cells were derived from the peripheral blood. Furthermore, lectin perfusion studies demonstrated that CD34(+) cells derived from peripheral blood were almost uniformly incorporated into the lung vasculature. Finally, CD34(+) endothelial cells demonstrated a similar profile, but had enhanced transcriptional activity relative to CD34(-) endothelial cells. We conclude that blood-borne CD34(+) endothelial progenitor cells, characterized by active cell division and an amplified transcriptional signature, transition into resident endothelial cells during compensatory lung growth.

Angiogenesis gene expression in murine endothelial cells during post-pneumonectomy lung growth.

Although blood vessel growth occurs readily in the systemic bronchial circulation, angiogenesis in the pulmonary circulation is rare. Compensatory lung growth after pneumonectomy is an experimental model with presumed alveolar capillary angiogenesis. To investigate the genes participating in murine neoalveolarization, we studied the expression of angiogenesis genes in lung endothelial cells. After left pneumonectomy, the remaining right lung was examined on days 3, 6, 14 and 21 days after surgery and compared to both no surgery and sham thoracotomy controls. The lungs were enzymatically digested and CD31+ endothelial cells were isolated using flow cytometry cell sorting. The transcriptional profile of the CD31+ endothelial cells was assessed using quantitative real-time polymerase chain reaction (PCR) arrays. Focusing on 84 angiogenesis-associated genes, we identified 22 genes with greater than 4-fold regulation and significantly enhanced transcription (p <.05) within 21 days of pneumonectomy. Cluster analysis of the 22 genes indicated that changes in gene expression did not occur in a single phase, but in at least four waves of gene expression: a wave demonstrating decreased gene expression more than 3 days after pneumonectomy and 3 sequential waves of increased expression on days 6, 14, and 21 after pneumonectomy. These findings indicate that a network of gene interactions contributes to angiogenesis during compensatory lung growth.

Intravascular pillars and pruning in the extraembryonic vessels of chick embryos.

To investigate the local mechanical forces associated with intravascular pillars and vessel pruning, we studied the conducting vessels in the extraembryonic circulation of the chick embryo. During the development days 13-17, intravascular pillars and blood flow parameters were identified using fluorescent vascular tracers and digital time-series video reconstructions. The geometry of selected vessels was confirmed by corrosion casting and scanning electron microscopy. Computational simulations of pruning vessels suggested that serial pillars form along pre-existing velocity streamlines; blood pressure demonstrated no obvious spatial relationship with the intravascular pillars. Modeling a Reynolds number of 0.03 produced 4 pillars at approximately 20-µm intervals matching the observed periodicity. In contrast, a Reynolds number of 0.06 produced only 2 pillars at approximately 63-µm intervals. Our modeling data indicated that the combination of wall shear stress and gradient of shear predicted the location, direction, and periodicity of developing pillars.

Blood flow shapes intravascular pillar geometry in the chick chorioallantoic membrane.

The relative contribution of blood flow to vessel structure remains a fundamental question in biology. To define the influence of intravascular flow fields, we studied tissue islands--here defined as intravascular pillars--in the chick chorioallantoic membrane. Pillars comprised 0.02 to 0.5% of the vascular system in 2-dimensional projection and were predominantly observed at vessel bifurcations. The bifurcation angle was generally inversely related to the length of the pillar (R = -0.47, P < .001). The pillar orientation closely mirrored the axis of the dominant vessel with an average variance of 5.62 +/- 6.96 degrees (p = .02). In contrast, the variance of pillar orientation relative to nondominant vessels was 36.78 +/- 21.33 degrees (p > .05). 3-dimensional computational flow simulations indicated that the intravascular pillars were located in regions of low shear stress. Both wide-angle and acute-angle models mapped the pillars to regions with shear less than 1 dyn/cm2. Further, flow modeling indicated that the pillars were spatially constrained by regions of higher wall shear stress. Finally, the shear maps indicated that the development of new pillars was limited to regions of low shear stress. We conclude that mechanical forces produced by blood flow have both a limiting and permissive influence on pillar development in the chick chorioallantoic membrane.