Relationship of Aortic Bifurcation with Sacropelvi...
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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Δευτέρα 6 Απριλίου 2020
Medicine by Alexandros G. Sfakianakis
Relationship of Aortic Bifurcation with Sacropelvi...
Relationship of Aortic Bifurcation with Sacropelvic Anatomy: Application to Anterior Lumbar Interbody Fusion
Relationship of Aortic Bifurcation with Sacropelvic Anatomy: Application to Anterior Lumbar Interbody Fusion:
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Abstract
Introduction
Various sacropelvic parameters such as the Pelvic Incidence (PI) are used to predict ideal lumbar lordosis and aid surgical planning. The objective of this study was to establish the relationship between the location of the aortic bifurcation from the sacral promontory and sacropelvic measures including the PI.Materials and Methods
165 CT scans obtained for major trauma including the entire spine were identified. Sacropelvic parameters including Pelvic Incidence (PI), Sacral Anatomic Orientation (SAO), Pelvic Thickness (PTH) and, Sacral Table Angle (STA) were measured. Aortic bifurcation was identified on sagittal and coronal imaging and the distance from the sacral promontory (BPD) measured (mm).Results
Mean age of the cohort was 44.3 years (s.d. 18.5; range 16–88 years); 61.8% male. The mean PI was 49.2° (s.d. 10.2°; range 30°‐80°). The mean BPD was 66.4 mm (s.d. 13.1 mm; range 38.3‐100 mm). In the majority the bifurcation was at the level of the L4 vertebral body (72.7%). Only age (r = −0.389; p < 0.0001) and PTH (r = 0.172; p = 0.027) correlated with the BPD to a significant degree. PI did not correlate with BPD (r = 0.061; p = 0.435). Linear regression analysis provided the following predictive equation: BPD = 34.3 mm + 0.30 x PTH.Conclusion
This study demonstrates a lack of any meaningful correlation between sagittal pelvic parameters and the distance of the aortic bifurcation from the sacral promontory. Surgical planning for fusion surgery in the lumbar spine should include assessment of spinopelvic parameters and if anterior access to the lumbar disc(s) necessary, vascular anatomy should be carefully assessed independent of these measures.This article is protected by copyright. All rights reserved.
The Membranous Septum Revisited – a Glimpse of our Anatomical Past
The Membranous Septum Revisited – a Glimpse of our Anatomical Past:
This article is protected by copyright. All rights reserved.
Abstract
The so‐called membranous septum is the fibrous component of the septal structures within the heart. It is relatively subtle in its appearance, but of considerable significance to the understanding of cardiac function and cardiac disease, both congenital and acquired. Surprisingly, its existence was seemingly unknown until the early decades of the ninetieth century. At this time, those writing in the English language described it as the “undefended space”, recognizing its importance in the setting of its aneurysmal dilation, and as the site of septal defects. By the initial decade of the twentieth century, it had come to be recognized as the landmark to the site of atrioventricular bundle. Over the first decade of the 21st century, its clinical significance has been emphasized in the context of transcutaneous replacement of the aortic valve. In this review, we describe our own recent investigations of this fibrous part of the septal structures. At the same time, we provide a glimpse of our anatomic past, explaining how its initial description relied on the observations of young physicians taking their first steps in the investigation of cardiac anatomy.This article is protected by copyright. All rights reserved.
Co‐targeting BET proteins and MCL1 induces synergistic cell death in melanoma
Co‐targeting BET proteins and MCL1 induces synergistic cell death in melanoma:
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Abstract
The treatment of melanoma has been markedly improved by the introduction of targeted therapies and checkpoint blockade immunotherapy. Unfortunately, resistance to these therapies remains a limitation. Novel anti‐cancer therapeutics targeting the MCL1 anti‐apoptotic protein have shown impressive responses in haematological cancers but are yet to be evaluated in melanoma. To assess the sensitivity of melanoma to new MCL1 inhibitors, we measured the response of 51 melanoma cell lines to the novel MCL1 inhibitor, S63845. Additionally, we assessed combination of this drug with inhibitors of the bromodomain and extra‐terminal (BET) protein family of epigenetic readers, which we postulated would assist MCL1 inhibition by downregulating anti‐apoptotic targets regulated by NF‐kB such as BCLXL, BCL2A1 and XIAP, and by upregulating pro‐apoptotic proteins including BIM and NOXA. Only 14% of melanoma cell lines showed sensitivity to S63845, however, combination of S63845 and I‐BET151 induced highly synergistic apoptotic cell death in all melanoma lines tested and in an in vivo xenograft model. Cell death was dependent on caspases and BAX/BAK. Although the combination of drugs increased the BH3‐only protein, BIM, and downregulated anti‐apoptotic proteins such as BCL2A1, the importance of these proteins in inducing cell death varied between cell‐lines. ABT‐199 or ABT‐263 inhibitors against BCL2 or BCL2 and BCLXL respectively, induced further cell death when combined with S63845 and I‐BET151. The combination of MCL1 and BET inhibition appears to be a promising therapeutic approach for metastatic melanoma, and presents opportunities to add further BCL2 family inhibitors to overcome treatment resistance.This article is protected by copyright. All rights reserved.
Past, presence and future of allergen immunotherapy vaccines
Past, presence and future of allergen immunotherapy vaccines:
Abstract
Allergen‐specific immunotherapy (AIT) is an allergen‐specific form of treatment for patients suffering from immunoglobulin E (IgE)‐associated allergy, the most common and important immunologically‐mediated hypersensitivity disease. AIT is based on the administration of the disease‐causing allergen with the goal to induce a protective immunity consisting of allergen‐specific blocking IgG antibodies and alterations of the cellular immune response so that the patient can tolerate allergen contact. Major advantages of AIT over all other existing treatments for allergy are that AIT induces a long‐lasting protection and prevents the progression of disease to severe manifestations. AIT is cost‐effective because it uses the patient´s own immune system for protection and potentially can be used as a preventive treatment. However, broad application of AIT is limited by mainly technical issues such as the quality of allergen preparations and the risk of inducing side effects which results in extremely cumbersome treatment schedules reducing patient´s compliance. In this article we review progress in AIT made from its beginning and provide an overview of the state of the art, the needs for further development and possible technical solutions available through molecular allergology. Finally, we consider visions for AIT development towards prophylactic application.Case of medullary thyroid carcinoma with desmoid‐type fibromatosis
Case of medullary thyroid carcinoma with desmoid‐type fibromatosis:
Abstract
A 36‐year‐old man was admitted to hospital for a right thyroid nodule incidentally discovered on a chest computed tomography scan for a rib fracture. He had no history of radiation to the head and neck, no known family history of endocrine disease, and no medical or surgical history. A 17 × 10 mm, well‐demarcated, multinodular, whitish nodule with neither necrosis nor hemorrhage was found in the right thyroid. Microscopically, the tumor consisted of epithelial cell nests with oval, plasmacytoid or polygonal cells with speckled chromatin, inconspicuous nucleoli and granular cytoplasm. The surrounding stroma showed amyloid deposition and prominent spindle cell proliferation with myxoid substance. Epithelial cell nests showed an immunoreactive pattern for typical medullary thyroid carcinoma (MTC), and the spindle cell stroma showed nuclear expression of beta‐catenin. This may be the first report on histopathologic findings of MTC with desmoid‐type fibromatosis. Further studies are necessary to discover the clinicopathologic characteristics and pathogenesis of this rare type of tumor.Acquired resistance to trastuzumab/pertuzumab or to T‐DM1 in vivo can be overcome by HER2 kinase inhibition with TAS0728
Acquired resistance to trastuzumab/pertuzumab or to T‐DM1 in vivo can be overcome by HER2 kinase inhibition with TAS0728:
Abstract
HER2‐targeting antibodies (trastuzumab, pertuzumab) and a HER2‐directed antibody‐drug conjugate (trastuzumab emtansine: T‐DM1) are used for the treatment of HER2‐overexpressing breast cancer. However, these treatments eventually become ineffective due to acquired resistance and there is an urgent need for alternative therapies. TAS0728 is a small‐molecule, irreversible selective HER2 kinase inhibitor. In the present study, we established new in vivo models of cancer resistance by continuous exposure to a combination of trastuzumab and pertuzumab or to T‐DM1 for evaluating the effect of TAS0728 on HER2 antibodies‐resistant populations. Treatment with trastuzumab and pertuzumab or with T‐DM1 initially induced tumor regression in NCI‐N87 xenografts. However, tumor regrowth during treatment indicated loss of drug effectiveness. In tumors with acquired resistance to trastuzumab and pertuzumab or to T‐DM1, HER2‐HER3 phosphorylation was retained in the tumors. Switching to TAS0728 resulted in a significant anti‐tumor effect associated with HER2‐HER3 signal inhibition. No alternative receptor tyrosine kinase (RTK) activation was observed in these resistant tumors. Furthermore, in a patient‐derived xenograft model derived from breast cancer refractory to both trastuzumab/pertuzumab and T‐DM1, TAS0728 exerted a potent anti‐tumor effect. These results suggest that tumors with acquired resistance to trastuzumab and pertuzumab and to T‐DM1 are still dependent on oncogenic HER2‐HER3 signaling and are vulnerable to HER2 signal inhibition by TAS0728. These results provide a rationale for TAS0728 therapy for breast cancers that are refractory to established anti‐HER2 therapies.Diagnostic performance of peripheral leukocyte telomere G‐tail length for detecting breast cancer
Diagnostic performance of peripheral leukocyte telomere G‐tail length for detecting breast cancer: 
Telomere G‐tail length correlates with the presence of breast cancer.
Telomere G‐tail length correlates with the presence of breast cancer.
Abstract
The telomere G‐tail (G‐tail) plays an essential role in maintaining chromosome stability. In this study, we assessed the leukocyte G‐tail length of breast cancer (BC) patients and cancer‐free individuals and evaluated the association between the G‐tail length and the presence of BC. A significant shortening of the median G‐tail length was observed in BC patients compared with cancer‐free individuals and was found in the early phase of BC. Our study indicated that the leukocyte G‐tail length might be a potential biomarker for BC detection.
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