Background: Frailty increases morbidity and mortality in patients with advanced heart and lung disease. Emerging evidence shows that postoperative cardiac or pulmonary rehabilitation can improve the frailty status of these patients. The aim of this hypothesis-generating study was to test the relationship between prehabilitation and frailty in patients with advanced heart or lung disease referred for heart and lung transplantation.
View Article and Find Full Text PDFBackground: Individuals with leprosy are at risk of leprosy reactions, T-cell mediated immunological complications, which lead to nerve function impairment. Leprosy reactions require systemic immunosuppression which is a risk factor for severe COVID-19. Vaccination for SARS-CoV-2 infection is recommended in the UK and became widely available in 2021 with individuals at increased risk of severe disease, including the immunosuppressed, prioritised.
View Article and Find Full Text PDFLongitudinal bone growth, achieved through endochondral ossification, is accomplished by a cartilaginous structure, the physis or growth plate, comprised of morphologically distinct zones related to chondrocyte function: resting, proliferating and hypertrophic zones. The resting zone is a stem cell-rich region that gives rise to the growth plate, and exhibits regenerative capabilities in response to injury. We discovered a FoxA2+group of long-term skeletal stem cells, situated at the top of resting zone, adjacent the secondary ossification center, distinct from the previously characterized PTHrP+ stem cells.
View Article and Find Full Text PDFBackground: Frailty is associated with adverse outcomes in advanced heart failure. We studied the impact of frailty on postoperative outcomes in bridge to transplant (BTT) durable mechanical circulatory support (MCS) recipients.
Methods: Patients undergoing left ventricular assist device (LVAD, n = 96) or biventricular support (BiV, n = 11) as BTT underwent frailty assessment.
We previously found that FoxA factors are necessary for chondrocyte differentiation. To investigate whether FoxA factors alone are sufficient to drive chondrocyte hypertrophy, we build a FoxA2 transgenic mouse in which FoxA2 cDNA is driven by a reiterated Tetracycline Response Element (TRE) and a minimal CMV promoter. This transgenic line was crossed with a col2CRE;Rosa26 mouse line to generate col2CRE;Rosa26;TgFoxA2 mice for inducible expression of FoxA2 in cartilage using doxycycline treatment.
View Article and Find Full Text PDFMutations in the isocitrate dehydrogenase 1 () and genes are frequently observed in a wide variety of hematologic malignancies, including myeloid and T-cell leukemias. In this study, we generated transgenic mice to examine the role of the mutation in leukemia. No leukemia developed in transgenic mice, suggesting a need for additional genetic events for leukemia development.
View Article and Find Full Text PDFBackground: The aim of this study was to validate our previous finding that frailty predicts early mortality in patients with advanced heart failure (AHF) and that including cognition in the frailty assessment enhances the prediction of mortality.
Methods: Patients with AHF referred to our Transplant Unit between November 2015 and April 2020 underwent physical frailty assessment using the modified Fried physical frailty (PF) phenotype as well as cognitive assessment using the Montreal Cognitive Assessment to identify patients who were cognitively frail (CogF). We assessed the predictive value of the 2 frailty measures (PF ≥ 3 of 5 = frail; CogF ≥ 3 of 6 = frail) for pretransplant mortality.
J Heart Lung Transplant
February 2021
Background: Frailty is prevalent in the patients with advanced heart failure; however, its impact on clinical outcomes after heart transplantation (HTx) is unclear. The aim of this study was to assess the impact of pre-transplant frailty on mortality and the duration of hospitalization after HTx.
Methods: We retrospectively reviewed the post-transplant outcomes of 140 patients with advanced heart failure who had undergone frailty assessment within the 6-month interval before HTx: 43 of them were frail (F) and 97 were non-frail (NF).
Loss of PTEN and loss of TP53 are common genetic aberrations occurring in prostate cancer. PTEN and TP53 contribute to the regulation of self-renewal and differentiation in prostate progenitors, presumptive tumor initiating cells for prostate cancer. Here we characterize the transformed phenotypes resulting from deletion of the Pten and TP53 tumor suppressors in prostate epithelium.
View Article and Find Full Text PDFLoss of PTEN is one of the most common mutations in prostate cancer, and loss of wild-type TP53 is associated with prostate cancer progression and castrate resistance. Modeling prostate cancer in the mouse has shown that while Pten deletion in prostate epithelial cells leads to adenocarcinoma, combined loss of Pten and TP53 results in rapidly developing disease with greater tumor burden and early death. TP53 contributes significantly to the regulation of stem cell self-renewal, and we hypothesized that loss of Pten/TP53 would result in measurable changes in prostate cancer stem/progenitor cell properties.
View Article and Find Full Text PDFThe t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1.
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