Thoracic Aortic Frontier: Review of Current Applications and Directions of Thoracic Endovascular Aortic Repair (TEVAR)

Thoracic endovascular aortic repair, a minimally invasive technique is replacing the maximally invasive gold standard of thoracotomy and replacement of the descending thoracic aorta. With experience, indications have expanded to encroach on the arch and even ascending aorta. This review highlights the current state of technology, discusses controversies, and takes the perspective of a forward-thinking review to describe novel, innovative techniques that might make the entire thoracic aorta amenable to minimally invasive repair.     

Discovery and Development of Potent and Selective Inhibitors of Histone Methyltransferase G9a

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Parenteral monofluorophosphate (MFP) is a more potent inducer of enamel fluorotic defects in neonatal hamster molars than sodium fluoride

Supra-optimal intake of sodium fluoride (NaF) during early childhood results in formation of irreversible enamel defects. Monofluorophosphate (MFP) was considered as less toxic than NaF but equally cariostatic. We compared the potency of MFP and NaF to induce pre-eruptive sub-ameloblastic cysts and post-eruptive white spots and pits in developing hamster enamel. Hamster pups were injected subcutaneously with either NaF or MFP in equimolar doses of either 9 mg or 18 mg F/kg body weight. At 9 mg F/kg, MFP induced more but smaller sub-ameloblastic cysts with a collective cyst volume twice as large as that induced by NaF. Eight days after F injection, all F-injected groups had formed 4–6 white spots per molar, with an additional 2 pits per molar in the low MFP group. Twenty-eight days after injection, most white spots had turned into pits (5–6 per molar) and only the high MFP group still contained 2 white spots per molar. We conclude that parenterally applied MFP is more potent in inducing enamel defects than NaF. Most white spots formed turn into pits by functional use of the dentition. The higher potency of parenteral MFP may be associated with sustained elevated F levels in the enamel organ by enzymatic hydrolysis of MFP by alkaline phosphatase activity.     

Motivation to Consent and Adhere to the FORT Randomized Controlled Trial

The aim of this qualitative study was to identify the motivational factors that influence cancer survivors to participate and adhere to the fear of cancer recurrence (FCR) FORT randomized controlled trial (RCT). Fifteen women diagnosed with breast and gynecological cancer who took part in the FORT RCT were interviewed about their experience to consent and adhere to the trial. The transcribed interviews were content analyzed within a relational autonomy framework. The analysis revealed that the participants’ motivation to consent and adhere to the FORT RCT was structured around thirteen subthemes grouped into four overarching themes: (1) Personal Influential Factors; (2) Societal Motivations; (3) Structural Influences; and (4) Gains in Emotional Support. The unique structures of the trial such as the group format, the friendships formed with other participants in their group and with the group leaders, and the right timing of the trial within their cancer survivorship trajectory all contributed to their motivation to consent and adhere to the FORT RCT. While their initial motivation to participate was mostly altruistic, it was their personal gains obtained over the course of the trial that contributed to their adherence. Potential gains in emotional and social support from psycho-oncology trials should be capitalized when approaching future participants as a mean to improve on motivations to consent and adhere.     

Combining Analysis of Tumor-infiltrating Lymphocytes (TIL) and PD-L1 Refined the Prognostication of Breast Cancer Subtypes

BackgroundPD-L1 has been used as a biomarker to select patients for treatment of PD-1/PD-L1 inhibitors.Materials and MethodsIn this study, we assessed the clinicopathological features of breast cancers that are associated with PD-L1 expression, as well as its relationship with other immune components and its prognostic significance.ResultsTotally 1752 cases were included in this cohort. PD-L1 expression in tumor-infiltrating immune cells (PD-L1-IC) expression and in tumor cells (PD-L1-TC) expression were identified in 34.2% and 10.1% of cases, respectively, and they showed a positive correlation with higher tumor grade, morphological apocrine features, presence of necrosis, and higher stromal tumor-infiltrating lymphocytes (sTIL). PD-L1-IC and PD-L1-TC expression correlated positively with each other, and both of them were negatively associated with estrogen receptor and progesterone receptor and positively associated with Ki67, HER2, EGFR, p63, and p-cadherin. In survival analysis, PD-L1-IC expression was associated with better disease-free survival (DFS) and breast cancer-specific survival (BCSS) in HER2-overexpressed (HER2-OE) cancers and high–grade luminal B cancers. In triple–negative breast cancers (TNBC) and HER2–OE cancers, compared with sTIL low PD-L1-IC negative cases, sTIL high cases showed significantly better DFS independent of PD-L1-IC status. sTIL low PD-L1-IC positive cases also demonstrated a better DFS in HER2–OE cancers. In high–grade luminal B cancers, sTIL high PD-L1-IC positive cases showed the best BCSS.ConclusionThe data suggested that the combining analysis of sTIL and PD-L1-IC expression refined the prognostication of breast cancer subtypes. Cases with high TIL and PD-LI-IC expression appear to be more immune active.