The shortage of donor organs highlights the need to better identify patients most likely to benefit from hepatic transplantation. Reduced aerobic capacity (decreased peak oxygen consumption [V O 2 ] during symptom-limited cardiopulmonary exercise testing) is frequently present in cirrhosis. Peak V O 2 during cardiopulmonary exercise testing may predict short-term outcome after hepatic transplantation. Symptom-limited testing was performed on a cycle ergometer (continuous ramp protocol) and V O 2 determined using a metabolic cart. One hundred fifty-six patients were tested; 59 subsequently underwent hepatic transplantation. Results showed that survivors and nonsurvivors were similar in age, duration of liver disease, Child-Pugh score, MELD score, resting cardiovascular function, pulmonary function, and gas exchange. The 6 (10.2%) patients dying within 100 days of transplantation were more likely to have reduced aerobic capacity (peak V O 2 <60% predicted and V O 2 at anaerobic threshold [V O 2 -AT ] <50% predicted peak V O 2 ) compared to survivors (4/6 vs. 7/53, P < .01). Using a multiple logistic regression model controlling for duration and severity of liver disease and time to transplantation, reduced aerobic capacity was independently associated with 100-day mortality. In conclusion, reduced aerobic capacity during cardiopulmonary exercise testing is associated with decreased short-term survival after hepatic transplantation. Further study is needed to determine if cardiopulmonary exercise testing can be used to improve allocation of donor organs. To ensure optimum allocation of donor organs, it is important to identify patients most likely to benefit from It has been increasingly recognized that exercise limitation and reduced aerobic capacity are common in patients with end-stage liver disease. 1-3 Patients with cirrhosis demonstrate decreased peak oxygen consumption (V O 2 ) and oxygen consumption at the anaerobic threshold (V O 2 -AT) during symptom-limited cardiopulmonary exercise testing when compared to noncirrhotic controls. 2 Cardiopulmonary exercise testing, with determination of peak oxygen uptake, has been investigated as a predictor of cardiopulmonary complications in patients undergoing noncardiac thoracic surgery 4 -7 and major abdominal surgery. 8 We hypothesize that cardiopulmonary exercise testing, with determination of peak V O 2 , may predict short-term outcome of hepatic transplantation.
Pulpal revascularization is commonly used in the dental clinic to obtain apical closure of immature permanent teeth with thin dentinal walls. Although sometimes successful, stimulating bleeding from the periapical area of the tooth can be challenging and in turn may deleteriously affect tooth root maturation. Our objective here was to define reliable methods to regenerate pulp-like tissues in tooth root segments (RSs). G1 RSs were injected with human dental pulp stem cells (hDPSCs) and human umbilical vein endothelial cells (HUVECs) encapsulated in 5% gelatin methacrylate (GelMA) hydrogel. G2 RSs injected with acellular GelMA alone, and G3 empty RSs were used as controls. White mineral trioxide aggregate was used to seal one end of the tooth root segment, while the other was left open. Samples were cultured in vitro in osteogenic media (OM) for 13 d and then implanted subcutaneously in nude rats for 4 and 8 wk. At least 5 sample replicates were used for each experimental group. Analyses of harvested samples found that robust pulp-like tissues formed in G1, GelMA encapsulated hDPSC/ HUVEC-filled RSs, and less cellularized host cell-derived pulp-like tissue was observed in the G2 acellular GelMA and G3 empty RS groups. Of importance, only the G1, hDPSC/HUVEC-encapsulated GelMA constructs formed pulp cells that attached to the inner dentin surface of the RS and infiltrated into the dentin tubules. Immunofluorescent (IF) histochemical analysis showed that GelMA supported hDPSC/HUVEC cell attachment and proliferation and also provided attachment for infiltrating host cells. Human cell-seeded GelMA hydrogels promoted the establishment of well-organized neovasculature formation. In contrast, acellular GelMA and empty RS constructs supported the formation of less organized host-derived vasculature formation. Together, these results identify GelMA hydrogel combined with hDPSC/HUVECs as a promising new clinically relevant pulpal revascularization treatment to regenerate human dental pulp tissues.
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