BackgroundThe aim of this study was to assess the relationship between extracorporeal blood flow (EBF) and left ventricular (LV) performance during venoarterial extracorporeal membrane oxygenation (VA ECMO) therapy.MethodsFive swine (body weight 45 kg) underwent VA ECMO implantation under general anesthesia and artificial ventilation. Subsequently, acute cardiogenic shock with signs of tissue hypoxia was induced. Hemodynamic and cardiac performance parameters were then measured at different levels of EBF (ranging from 1 to 5 L/min) using arterial and venous catheters, a pulmonary artery catheter and a pressure–volume loop catheter introduced into the left ventricle.ResultsMyocardial hypoxia resulted in a decline in mean (±SEM) cardiac output to 2.8 ± 0.3 L/min and systolic blood pressure (SBP) to 60 ± 7 mmHg. With an increase in EBF from 1 to 5 L/min, SBP increased to 97 ± 8 mmHg (P < 0.001); however, increasing EBF from 1 to 5 L/min significantly negatively influences several cardiac performance parameters: cardiac output decreased form 2.8 ± 0.3 L/min to 1.86 ± 0.53 L/min (P < 0.001), LV end-systolic volume increased from 64 ± 11 mL to 83 ± 14 mL (P < 0.001), LV stroke volume decreased from 48 ± 9 mL to 40 ± 8 mL (P = 0.045), LV ejection fraction decreased from 43 ± 3 % to 32 ± 3 % (P < 0.001) and stroke work increased from 2096 ± 342 mmHg mL to 3031 ± 404 mmHg mL (P < 0.001). LV end-diastolic pressure and volume were not significantly affected.ConclusionsThe results of the present study indicate that higher levels of VA ECMO blood flow in cardiogenic shock may negatively affect LV function. Therefore, it appears that to mitigate negative effects on LV function, optimal VA ECMO blood flow should be set as low as possible to allow adequate tissue perfusion.
Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion. Hyalinizing clear cell carcinoma is a low-grade tumor with infrequent nodal and distant metastasis, recently shown to harbor an EWSR1-ATF1 gene fusion. The CRTC1-MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low-grade and high-grade mucoepidermoid carcinomas associated with improved survival. A t(6;9)(q22-23;p23-34) translocation resulting in a MYB-NFIB gene fusion has been identified in the majority of adenoid cystic carcinomas. Polymorphous (low-grade) adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin are related entities with partly differing clinicopathologic and genomic profiles; they are the subject of an ongoing taxonomic debate. Polymorphous (low-grade) adenocarcinomas are characterized by hot spot point E710D mutations in the PRKD1 gene, whereas cribriform adenocarcinoma of (minor) salivary glands origin are characterized by translocations involving the PRKD1-3 genes. Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with morphologic and molecular features akin to invasive ductal carcinoma of the breast, including HER2 gene amplification, mutations of TP53, PIK3CA, and HRAS and loss or mutation of PTEN. Notably, a recurrent NCOA4-RET fusion has also been found in SDC. A subset of SDC with apocrine morphology is associated with overexpression of androgen receptors. As these genetic aberrations are recurrent they serve as powerful diagnostic tools in salivary gland tumor diagnosis, and therefore also in refinement of salivary gland cancer classification. Moreover, they are promising as prognostic biomarkers and targets of therapy.
ETV6 gene abnormalities are well described in tumor pathology. Many fusion partners of ETV6 have been reported in a variety of epithelial, mesenchymal, and hematological malignancies. In salivary gland tumor pathology, however, the ETV6-NTRK3 translocation is specific for (mammary analog) secretory carcinoma, and has not been documented in any other salivary tumor type. The present study comprised a clinical, histologic, and molecular analysis of 10 cases of secretory carcinoma, with typical morphology and immunoprofile harboring a novel ETV6-RET translocation.
IntroductionExtracorporeal membrane oxygenation (ECMO) is increasingly used in cardiac arrest (CA). Adequacy of carotid and coronary blood flows (CaBF, CoBF) and coronary perfusion pressure (CoPP) in ECMO treated CA is not well established. This study compares femoro-femoral (FF) to femoro-subclavian (FS) ECMO and intraaortic balloon counterpulsation (IABP) contribution based on CaBF, CoBF, CoPP, myocardial and brain oxygenation in experimental CA managed by ECMO.MethodsIn 11 female pigs (50.3 ± 3.4 kg), CA was randomly treated by FF versus FS ECMO ± IABP. Animals under general anesthesia had undergone 15 minutes of ventricular fibrillation (VF) with ECMO flow of 5 to 10 mL/kg/min simulating low-flow CA followed by continued VF with ECMO flow of 100 mL/kg/min. CaBF and CoBF were measured by a Doppler flow wire, cerebral and peripheral oxygenation by near infrared spectroscopy. CoPP, myocardial oxygen metabolism and resuscitability were determined.ResultsCaBF reached values > 80% of baseline in all regimens. CoBF > 80% was reached only by the FF ECMO, 90.0% (66.1, 98.6). Addition of IABP to FF ECMO decreased CoBF to 60.7% (55.1, 86.2) of baseline, P = 0.004. FS ECMO produced 70.0% (49.1, 113.2) of baseline CoBF, significantly lower than FF, P = 0.039. Addition of IABP to FS did not change the CoBF; however, it provided significantly higher flow, 76.7% (71.9, 111.2) of baseline, compared to FF + IABP, P = 0.026. Both brain and peripheral regional oxygen saturations decreased after induction of CA to 23% (15.0, 32.3) and 34% (23.5, 34.0), respectively, and normalized after ECMO institution. For brain saturations, all regimens reached values exceeding 80% of baseline, none of the comparisons between respective treatment approaches differed significantly. After a decline to 15 mmHg (9.5, 20.8) during CA, CoPP gradually rose with time to 68 mmHg (43.3, 84.0), P = 0 .003, with best recovery on FF ECMO. Resuscitability of the animals was high, both 5 and 60 minutes return of spontaneous circulation occured in eight animals (73%).ConclusionsIn a pig model of CA, both FF and FS ECMO assure adequate brain perfusion and oxygenation. FF ECMO offers better CoBF than FS ECMO. Addition of IABP to FF ECMO worsens CoBF. FF ECMO, more than FS ECMO, increases CoPP over time.
The role of nonclassical human leukocyte antigens G and E (HLA-G and HLA-E) was originally thought to be restricted to the protection of the fetus from a maternal allorecognition. Now it is known that HLA-G and HLA-E exert multiple immunoregulatory functions. A prognostic significance of the expression of HLA-G and HLA-E by neoplastic cells in glioblastoma is not well characterized. In this study, we evaluated the expression of HLA-G and HLA-E by neoplastic cells in 39 cases of glioblastoma. We found the production of HLA-G and HLA in a majority of cases. There was an unexpected positive correlation between the expression of HLA-E and length of survival. We speculate that the expression of this molecule by neoplastic cells may represent a coincidental selective pro-host advantage related to better response to subsequent therapeutic modalities. Mechanisms of glioblastoma cell pathophysiology and mechanisms of responses to therapeutic interventions in respect to the expression of these molecules deserves further study.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.