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Chrystalle Katte Carreon Annachiara Benini Christopher Baird David Hoganson Michele Borisuk Sitaram Emani Sophie Hofferberth Robert F. Padera Stephen P. Sanders 《The Journal of thoracic and cardiovascular surgery》2019,157(1):342-350.e3
Objectives
Although valved venous homografts (VVHs) are used for establishing right ventricle-to-pulmonary artery continuity in some complex heart defects, the tissue changes that occur in situ have not been described. We review the gross and microscopic changes observed in explanted VVH conduits and their effects on functionality.Methods
In total, 20 explanted VVH conduits were evaluated for valve integrity, presence of thrombus, and stenosis. Hematoxylin and eosin– and trichrome-stained sections were reviewed for neointima formation, wall remodeling, inflammation, and calcification. Regurgitation and narrowing were assessed on pre-explant echocardiogram, and angiographic video clips were correlated with tissue findings. The source of the proliferating cells within the conduits was investigated by fluorescent in situ hybridization.Results
Thirteen male and 7 female infants underwent VVH implantation either as part of a composite Sano shunt (65%) or to establish right ventricle-to-pulmonary artery continuity in biventricular hearts (35%). The median duration of conduits in situ was 140 days (range: 98-340 days). Conduits were predominantly explanted for staged conversion to bidirectional Glenn (60%) and conduit upsizing (20%). The valves remained intact and functional in 75% of cases. Occlusive thrombosis was absent in all. Wall thickening due to neointima formation and wall remodeling was uniformly present and appeared to be driven by smooth muscle actin–expressing cells, which by fluorescent in situ hybridization are predominantly of recipient origin. Minimal calcification and mild adventitial chronic inflammation were present.Conclusions
Vein wall thickening is a uniform finding and can cause stenosis. The valves remain functional in most, and vein walls undergo remodeling with only minimal inflammation and calcification. 相似文献4.
Multiple opioids are known to trigger mast cell degranulation. We report the case of a neonate with blistering skin lesions at birth who died of multi‐organ failure after administration of morphine. Given the excessive histamine release and potential complications associated with morphine administration, alternative opioids and adjuvants should be considered in infants presenting with evidence of bullous or infiltrative skin lesions until mastocytosis is ruled out. 相似文献
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Dinja T. Kruger Xanthippi Alexi Mark Opdam Karianne Schuurman Leonie Voorwerk Joyce Sanders Vincent van der Noort Epie Boven Wilbert Zwart Sabine C. Linn 《International journal of cancer. Journal international du cancer》2020,146(8):2348-2359
Preclinical studies indicate that activated IGF-1R can drive endocrine resistance in ER-positive (ER+) breast cancer, but its clinical relevance is unknown. We studied the effect of IGF-1R signaling on tamoxifen benefit in patients and we searched for approaches to overcome IGF-1R-mediated tamoxifen failure in cell lines. Primary tumor blocks from postmenopausal ER+ breast cancer patients randomized between adjuvant tamoxifen versus nil were recollected. Immunohistochemistry for IGF-1R, p-IGF-1R/InsR, p-ERα(Ser118), p-ERα(Ser167) and PI3K/MAPK pathway proteins was performed. Multivariate Cox models were employed to assess tamoxifen efficacy. The association between p-IGF-1R/InsR and PI3K/MAPK pathway activation in MCF-7 and T47D cells was analyzed with Western blots. Cell proliferation experiments were performed under various growth-stimulating and -inhibiting conditions. Patients with ER+, IGF-1R-positive breast cancer without p-IGF-1R/InsR staining (n = 242) had tamoxifen benefit (HR 0.41, p = 0.0038), while the results for p-IGF-1R/InsR-positive patients (n = 125) were not significant (HR 0.95, p = 0.3). High p-ERα(Ser118) or p-ERα(Ser167) expression was associated with less tamoxifen benefit. In MCF-7 cells, IGF-1R stimulation increased phosphorylation of PI3K/MAPK proteins and ERα(Ser167) regardless of IGF-1R overexpression. This could be abrogated by the dual IGF-1R/InsR inhibitor linsitinib, but not by the IGF-IR-selective antibody 1H7. In MCF-7 and T47D cells, stimulation of the IGF-1R/InsR pathway resulted in cell proliferation regardless of tamoxifen. Abrogation of cell growth was regained by addition of linsitinib. In conclusion, p-IGF-1R/InsR positivity in ER+ breast cancer is associated with reduced benefit from adjuvant tamoxifen in postmenopausal patients. In cell lines, stimulation rather than overexpression of IGF-1R is driving tamoxifen resistance to be abrogated by linsitinib. 相似文献
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Christiane Horwood Lyn Haskins Ameena Goga Tanya Doherty Vaughn John Ingunn M.S. Engebretsen Ute Feucht Nigel Rollins Max Kroon David Sanders Thorkild Tylleskar 《Maternal & child nutrition》2020,16(2)
Clinical guidelines are used to translate research findings into evidence‐based clinical practice but are frequently not comprehensively adopted by health workers (HWs). HIV and infant feeding guidelines were revised by the World Health Organization to align feeding advice for HIV‐exposed and unexposed infants, and these were adopted in South Africa in 2017. We describe an innovative, team‐based, mentoring programme developed to update HWs on these guidelines. The intervention was underpinned by strong theoretical frameworks and aimed to improve HWs' attitudes, knowledge, confidence, and skills about breastfeeding in the context of HIV. On‐site workshops and clinical mentoring used interactive participatory methods and a simple low‐tech approach, guided by participants' self‐reported knowledge gaps. Workshops were conducted at 24 participating clinics over three sessions, each lasting 1–2 hr. Evaluation data were collected using a self‐administered questionnaire. Of 303 participating HWs, 249/303 (82.2%) attended all workshops. Achieving high workshop attendance was challenging and “catch‐up” sessions were required to achieve good coverage. Common knowledge gaps identified included antiretroviral therapy adherence monitoring during breastfeeding and management of viral load results (173 participants), management of breast conditions (79), and advice about expressing and storing breastmilk (64). Most participants reported all their knowledge gaps were addressed and anticipated that their practice would change. We describe a feasible, sustainable approach to updating HWs on HIV and infant feeding guidelines and improving skills in breastfeeding counselling in resource‐constrained settings. This approach could be adapted to other topics and, with further evaluation, implemented at scale using existing resources. 相似文献
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