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© The Author(s) 2020.Intraductal papillomas (IDP) are challenging breast findings because of their variable risk of progression to malignancy. The molecular events driving IDP development and genomic features of malignant progression are poorly understood. In this study, genome-wide CNA and/or targeted mutation analysis was performed on 44 cases of IDP, of which 20 cases had coexisting ductal carcinoma in situ (DCIS), papillary DCIS or invasive ductal carcinoma (IDC). CNA were rare in pure IDP, but 69% carried an activating PIK3CA mutation. Among the synchronous IDP cases, 55% (11/20) were clonally related to the synchronous DCIS and/or IDC, only one of which had papillary histology. In contrast to pure IDP, PIK3CA mutations were absent from clonal cases. CNAs in any of chromosomes 1, 16 or 11 were significantly enriched in clonal IDP lesions compared to pure and non-clonal IDP. The observation that 55% of IDP are clonal to DCIS/IDC indicates that IDP can be a direct precursor for breast carcinoma, not limited to the papillary type. The absence of PIK3CA mutations and presence of CNAs in IDP could be used clinically to identify patients at high risk of progression to carcinoma. © The Author(s) 2020.The genomics-based molecular classifications aim at identifying more homogeneous classes than immunohistochemistry, associated with a more uniform clinical outcome. We conducted an in silico analysis on a meta-dataset including gene expression data from 5342 clinically defined ER+/HER2- breast cancers (BC) and DNA copy number/mutational and proteomic data. We show that the Basal (16%) versus Luminal (74%) subtypes as defined using the 80-gene signature differ in terms of response/vulnerability to systemic therapies of BC. check details The Basal subtype is associated with better chemosensitivity, lesser benefit from adjuvant hormone therapy, and likely better sensitivity to PARP inhibitors, platinum salts and immune therapy, and other targeted therapies under development such as FGFR inhibitors. The Luminal subtype displays potential better sensitivity to CDK4/6 inhibitors and vulnerability to targeted therapies such as PIK3CA, AR and Bcl-2 inhibitors. Expression profiles are very different, showing an intermediate position of the ER+/HER2- Basal subtype between the ER+/HER2- Luminal and ER- Basal subtypes, and let suggest a different cell-of-origin. Our data suggest that the ER+/HER2- Basal and Luminal subtypes should not be assimilated and treated as a homogeneous group. © The Author(s) 2020.Background Weight change, primarily weight gain, is a common problem among solid organ transplant recipients. The incidence of weight gain or loss after successful pancreas transplant alone (PTA) and the effect on graft survival is unknown. Methods This was a single-center observational study among PTA recipients, transplanted at our center between January 1, 2005, and July 31, 2017, who had a functional pancreas graft for at least 1 year and documented weight change at the 1-year clinic visit. Results In this cohort study of 105 PTA recipients, 28 had significant weight gain, 27 had significant weight loss, and the remaining 50 did not have significant weight change at 1-year posttransplant. When comparing the weight gain and no weight change groups, the weight gain cohort started to gain weight at 3 months posttransplant to 5 years or last follow up. Similarly, the weight loss group lost weight at 3 months posttransplant up to last follow up. Clinically significant weight gain or weight loss were not associated with uncensored or death censored graft failure in univariate regression and Kaplan-Meier survival analysis. Also, there were no significant differences between the groups in the glycated hemoglobin at last follow up. Conclusions Approximately 50% of PTA recipients had a significant weight change at 1-year posttransplant, of which 25% gained significant weight and 25% loss. There was no significant difference in graft survival due to the significant weight changes. Further research is needed in this field. Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.Background Our aim was to investigate the bone mineral density (BMD) evolution and incidence of osteoporosis in relation to chronic kidney disease (CKD) up to 10 years after heart transplantation (HT). Methods A retrospective analysis was performed on 159 HT patients at Skåne University Hospital in Lund 1988-2016. Results The median follow-up time was 6.1 years (interquartile range = 7.5 y). HT patients with CKD stage less then 3 or normal kidney function before HT exhibited a greater mean BMD loss in the lumbar spine, compared to patients with CKD stage ≥3 before HT, at the first (-6.6% versus -2.5%, P = 0.029), second (-3.7% versus 2.1%, P = 0.018), and third (-2.0% versus 4.1%, P = 0.047) postoperative years, respectively. All included HT patients exhibited a BMD loss in the femoral neck at the first postoperative year (-8.8% [-10.3 to -7.3] in patients with CKD stage less then 3 or normal kidney function and -9.3% [-13.2 to -5.5] in patients with CKD stage ≥3 before HT), which was not fully reversed up to 10 years after HT. In adjusted models, CKD stage less then 3 before HT did not predict osteopenia and osteoporosis in the lumbar spine or femoral neck. Conclusions CKD before HT did not predict BMD loss or osteoporosis development after HT. The study is, however, limited by a lack of data on fractures, and further studies on the relationship between CKD and postoperative bone strength are encouraged. Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.Background Muslim communities tend to hold more negative attitudes toward organ donation than other communities. These views, in part, reflect the diverse views of Islamic scholars who debate the conditions under which donation and transplantation is morally licit. In December 2018, the Fiqh Council of North America (FCNA) weighed in on the US context of donation and transplantation through an Islamic ethico-legal verdict (fatwa). Methods Between 2016 and 2018, FCNA members engaged in multidisciplinary research using conventions of collective Islamic moral deliberation. They examined rulings on organ donation and transplantation issued by Islamic jurists and juridical councils abroad, convened with organ donation and transplantation professionals and stakeholders including families and patients, and consulted medical and bioethics experts. Results FCNA judges organ donation to be morally permissible from the perspective of Islamic law and ethics, subject to several conditions. These include first-person authorization, that donation occur either while living or after circulatory declaration of death, harm to the donor is minimized, reproductive organs are not donated, among others.
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