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1

Fink, Thomas, Feifan Ouyang, Christian-Hendrik Heeger, Vanessa Sciacca, Bruno Reissmann, Ahmad Keelani, Christopher Schütte, et al. "Management of thrombus formation after electrical isolation of the left atrial appendage in patients with atrial fibrillation." EP Europace 22, no. 9 (August 3, 2020): 1358–66. http://dx.doi.org/10.1093/europace/euaa174.

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Abstract Aims Left atrial appendage (LAA) electrical isolation (LAAEI) in addition to pulmonary vein isolation is an emerging catheter-based therapy to treat symptomatic atrial fibrillation. Previous studies found high incidences of LAA thrombus formation after LAAEI. This study sought to analyse therapeutic strategies aiming at the resolution of LAA thrombi and prevention of thromboembolism. Methods and results Left atrial appendage electrical isolation was conducted via creation of left atrial linear lesions or cryoballoon ablation. Follow-up including transoesophageal echocardiography was conducted. In patients with LAA thrombus, oral anticoagulation (OAC) was adjusted until thrombus resolution was documented. Percutaneous LAA closure (LAAC) under use of a cerebral protection device was conducted in case of medically refractory LAA thrombi. Left atrial appendage thrombus was documented in 54 of 239 analysed patients who had undergone LAAEI. Thrombus resolution was documented in 39/51 patients (72.2%) with available follow-up after adjustment of OAC. Twenty-nine patients underwent LAAC and 10 patients were kept on OAC after LAAEI. No thromboembolic events or further LAA thrombi were documented after 553 ± 443 days of follow-up in these patients. Persistent LAA thrombi despite adaption of OAC was documented in 12/51 patients. One patient remained on OAC until the end of follow-up, while LAAC with a cerebral protection device was performed in 11 patients in the presence of LAA thrombus without complications. Conclusion Left atrial appendage thrombus formation is common after LAAEI. Adjustment of OAC leads to LAA thrombus resolution in most patients. Left atrial appendage closure in the presence of LAA thrombi might be a feasible option in case of failed medical treatment.
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Borowski, Finja, Sebastian Kaule, Stefan Siewert, Klaus-Peter Schmitz, Michael Stiehm, Alper Ö. Öner, Niels Grabow, and Klaus-Peter Schmitz. "Development of an in vitro test procedure for the characterization of left atrial appendage occluder devices." Current Directions in Biomedical Engineering 5, no. 1 (September 1, 2019): 461–63. http://dx.doi.org/10.1515/cdbme-2019-0116.

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AbstractThe implantation of an occluder in the left atrial appendage (LAA) is an emerging therapy for the treatment of patients suffering from atrial fibrillation and with a contraindication to oral anticoagulation. The LAA occluder (LAAO) provides a reduction of the potential risk of strokes by thromboembolism. Currently, only a few CE-approved devices are available on the market and the number of clinical trials is comparatively low. Furthermore, there is currently no standardized test method available for testing functionality of the occluder, especially for testing safe anchorage and permeability. Therefore, the aim of this study is to establish an in vitro test method to prove anchorage mechanism and permeability regarding thromboembolism of the LAAO under physiological conditions. A standardized technical and fully parameterized silicone model of a LAA, based on studies of different morphologies and sizes, was developed. The LAA model was mounted onto the left atrial chamber of a commercial pulse duplicator system to simulate physiological hemodynamic conditions. The test was performed using the Watchman device (Boston Scientific, USA; size: 31 mm). The inner implantation diameter of the LAA model was designed according to a target compression of 10% for the Watchman device in the implanted configuration. Furthermore, thrombus-like particles (n=150, d=1,7±0,05 mm) were added to represent the flushing of thrombi out of the LAA after device implantation. Within several cycles it was confirmed that no particles were washed out of the LAA model with the implanted occluder leading to a full protection against thromboembolism. It could also be shown that the occluder is firmly anchored in the LAA. Pressure measurements with sensors in the left atrium and in the LAA distal to the occluder could also show that the occluder has no influence on the pressure conditions in the LAA.
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Tinggaard, Andreas Bugge, Kasper Korsholm, Jesper Møller Jensen, and Jens Erik Nielsen-Kudsk. "Spontaneously occluded left atrial appendage in a patient with atrial fibrillation and stroke: a case report." European Heart Journal - Case Reports 4, no. 2 (February 27, 2020): 1–4. http://dx.doi.org/10.1093/ehjcr/ytaa027.

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Abstract Background The left atrial appendage (LAA) is the main source of thromboembolism in atrial fibrillation (AF). Transcatheter closure is non-inferior to warfarin therapy in preventing stroke. Case summary A patient with two consecutive strokes associated with AF was referred for transcatheter LAA occlusion (LAAO). Preprocedural cardiac CT and transoesophageal echocardiography demonstrated a spontaneously occluded LAA with a smooth left atrial surface, with stationary results at 6- and 12-month imaging follow-up. Warfarin was discontinued, and life-long aspirin instigated. Discussion Left atrial appendage occlusion has shown non-inferiority to warfarin for prevention of stroke, cardiovascular death, and all-cause mortality. No benefits from anticoagulation have been demonstrated in patients with embolic stroke of undetermined source. In the present case, we observed that the LAA was occluded and, therefore, treated with aspirin monotherapy assuming similar efficacy as transcatheter LAAO.
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Liu, Peng, Rijing Liu, Yan Zhang, Yingfeng Liu, Xiaoming Tang, and Yanzhen Cheng. "The Value of 3D Printing Models of Left Atrial Appendage Using Real-Time 3D Transesophageal Echocardiographic Data in Left Atrial Appendage Occlusion: Applications toward an Era of Truly Personalized Medicine." Cardiology 135, no. 4 (2016): 255–61. http://dx.doi.org/10.1159/000447444.

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Aims and Objectives: The objective of this study was to assess the clinical feasibility of generating 3D printing models of left atrial appendage (LAA) using real-time 3D transesophageal echocardiogram (TEE) data for preoperative reference of LAA occlusion. Background: Percutaneous LAA occlusion can effectively prevent patients with atrial fibrillation from stroke. However, the anatomical structure of LAA is so complicated that adequate information of its structure is essential for successful LAA occlusion. Emerging 3D printing technology has the demonstrated potential to structure more accurately than conventional imaging modalities by creating tangible patient-specific models. Typically, 3D printing data sets are acquired from CT and MRI, which may involve intravenous contrast, sedation, and ionizing radiation. It has been reported that 3D models of LAA were successfully created by the data acquired from CT. However, 3D printing of the LAA using real-time 3D TEE data has not yet been explored. Methods: Acquisition of 3D transesophageal echocardiographic data from 8 patients with atrial fibrillation was performed using the Philips EPIQ7 ultrasound system. Raw echocardiographic image data were opened in Philips QLAB and converted to ‘Cartesian DICOM' format and imported into Mimics® software to create 3D models of LAA, which were printed using a rubber-like material. The printed 3D models were then used for preoperative reference and procedural simulation in LAA occlusion. Results: We successfully printed LAAs of 8 patients. Each LAA costs approximately CNY 800-1,000 and the total process takes 16-17 h. Seven of the 8 Watchman devices predicted by preprocedural 2D TEE images were of the same sizes as those placed in the real operation. Interestingly, 3D printing models were highly reflective of the shape and size of LAAs, and all device sizes predicted by the 3D printing model were fully consistent with those placed in the real operation. Also, the 3D printed model could predict operating difficulty and the presence of a peridevice leak. Conclusions: 3D printing of the LAA using real-time 3D transesophageal echocardiographic data has a perfect and rapid application in LAA occlusion to assist with physician planning and decision making.
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Sun, Xuejun, Dandan Hong, Haibo Liu, and Hongmu Li. "Acute Mitral Valve Injury Following Percutaneous Left Atrial Appendage Occlusion: A Case Report and Literature Review." Heart Surgery Forum 23, no. 6 (October 13, 2020): E743—E745. http://dx.doi.org/10.1532/hsf.3157.

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Acute mitral valve injury following percutaneous left atrial appendage (LAA) occlusion is a rare, but potentially life-threatening complication. This report presents a case of severe mitral valve injury following left atrial appendage occlusion (LAAO) that required mitral valve replacement. The LAAO device successfully was removed, and the LAA was closed with a double-running polypropylene suture. In addition, the mitral valve was replaced with an artificial valve. The patient had an uneventful clinical evolution and was discharged 10 days after emergency surgery.
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6

Ward, Alison F., Robert M. Applebaum, Nana Toyoda, Ans Fakiha, Peter J. Neuburger, Jennie Ngai, Robert G. Nampiaparampil, David W. Yaffee, Didier F. Loulmet, and Eugene A. Grossi. "Totally Endoscopic Robotic Left Atrial Appendage Closure Demonstrates High Success Rate." Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery 12, no. 1 (January 2017): 46–49. http://dx.doi.org/10.1097/imi.0000000000000330.

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Objective In patients with atrial fibrillation, 90% of embolic strokes originate from the left atrial appendage (LAA). Successful exclusion of the LAA is associated with a lower stroke rate in patients with atrial fibrillation. Surgical oversewing of the LAA is often incomplete when evaluated with transesophageal echocardiogram (TEE). External closure techniques of suturing and stapling have also demonstrated high failure rates with persistent flow and large stumps. We hypothesized that the precise visualization of a robotic LAA closure (RLAAC) would result in superior closure rates. Methods Before robotic mitral repair, patients underwent RLAAC; the base of the LAA was oversewn using a running 4–0 polytetrafluoroethylene suture in two layers. Postoperatively, the LAA was interrogated in multiple TEE views. Incomplete closure was defined as any flow across the LAA suture line or a residual stump of greater than 1 cm. Results Seventy-nine consecutive patients underwent RLAAC; no injuries occurred. On postrepair TEE, 73 of 79 patients had LAAs visualized well enough to thoroughly evaluate. Successful ligation was confirmed in 64 (87.7%) of 73 patients. Seven patients (9.6%) had small jet flow into the LAA; no residual stumps were noted. Two patients (2.7%) had undetermined flow. Conclusions We have demonstrated excellent success with RLAAC; we postulate that this may be due to improved intracardiac visualization. Robotic LAA closure was more successful (87.7%) than previously reported results from the Left Atrial Appendage Occlusion Study for suture exclusion (45.5%) and staple closure (72.7%). With success rates equivalent to transcatheter device closures, RLAAC should be considered for robotic mitral valve surgical patients.
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7

Ebelt, Henning, Sarah Goetze, Anja Weida, and Alexandra Offhaus. "Impact of ultrasound contrast agent during transoesophageal echocardiography on the sizing of the left atrial appendage." Open Heart 8, no. 1 (March 2021): e001403. http://dx.doi.org/10.1136/openhrt-2020-001403.

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IntroductionInterventional closure of the left atrial appendage closure (LAAC) has been established as an alternative treatment in patients with atrial fibrillation (AF) and an increased risk of stroke. So far it is unknown whether the use of ultrasound contrast agent (UCA) would influence the correct sizing of the LAA and thereby have an impact on device selection during interventional LAAC.MethodsBetween January 2017 and April 2018, 223 transoesophageal echocardiography (TOE) examinations were prospectively performed in adult patients with non-valvular AF (Impact of the use of ultrasound contrast agent on the detection of thrombi in the left atrial appendage during transesophageal echocardiography (CONDOR) study). LAA was examined both with and without the use of UCA. The following measurements were taken at 0o, 45o, 90o and 135o: diameter of LAA ostium, maximal depth of the LAA, maximal available depth of the LAA orthogonal to the ostial plane and area of the LAA.ResultsThe use of UCA had no relevant influence on the size determination of the LAA. Additionally, Bland-Altman blots demonstrate a high degree of correlation between the measurements with and without UCA with no evidence for a systematic effect arising from the use of UCA. When comparing the measurements of two independent investigators, the use of UCA rather leads to a higher variability than to an improved precision.DiscussionDespite the fact that the use of UCA during TOE leads to an improved rule out of thrombi, our study shows that there is no advantageous effect of UCA on the size determination of the LAA and should therefore not be used for this purpose.
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Voutiadou, Georgia, Konstantina Kotta, Barbara Tachynopoulou, Apostolia Papalexandri, Chryssanthi Vadikolia, Aliki Tsompanakou, Anastasia Athanasiadou, et al. "Acute Myeloid Leukemia with Coexpression of Lymphoid-Associated Antigens: Clinicobiological Associations and Prognostic Implications,." Blood 118, no. 21 (November 18, 2011): 3596. http://dx.doi.org/10.1182/blood.v118.21.3596.3596.

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Abstract Abstract 3596 Immune phenotyping plays a critical role in the diagnosis and classification of acute leukemia. Several studies have reported a variable proportion of patients with acute myeloid leukemia (AML) expressing lymphoid-associated antigens (LAA). The exact frequency and true clinical significance of this phenomenon remains undefined due to inconsistencies between series, likely related to methodological aspects or potential case selection biases. We retrospectively evaluated the expression of LAA in blast cells from 278 consecutive and unselected patients with AML diagnosed in our Department between 2002 and 2010. The patient cohort included 168 males and 110 females with a median age of 61 years (range, 10–88); 146/278 cases were above the age of 60. Within this cohort, 190 cases (68%) had de novo AML, whereas the remaining 88 cases (32%) concerned secondary AML (sAML) to either MDS (n=80) or other non-hematologic malignancies (n=8). Patients were treated uniformly according to age with Aracytin/Idarubicin induction regimens (“3+7” or “2+5” for ages \q60 or ≥60, respectively). The immunophenotype was determined by flow cytometric analysis of (mainly) bone marrow aspirate and/or peripheral blood samples utilizing a primary CD45/side scatter (SSC) gating procedure with antibodies against CD7, CD13, CD19, CD33, CD4, CD10, CD34, CD117, CD64, HLA-DR, CD20, CD2, CD15, CD56, CD14, CD8, MPO, CD3, CD79a, CD22, TdT and lysozyme; a cut-off value for positivity of 20% was adopted. Overall, we identified 153/278 cases (55%) expressing at least one LAA. The most commonly expressed LAAs were CD4 (outside AML with monocytic differentiation), CD56, CD7, CD2, CD10 and CD79a (in 39%, 33%, 29%, 14%, 10% and 8% of LAA+ AML cases, respectively); interestingly, all CD79a-positive cases co-expressed at least one more LAA. A significant association was identified between LAA expression and cytogenetic profile: in particular, at least one LAA was detected in 37/50 cases (74%) with adverse cytogenetics (SWOG unfavorable and/or monosomal karyotype), compared to 24/41 (58%) cytogenetically favorable cases and 68/134 (51%) cytogenetically intermediate risk cases (p=0.01). No other statistically significant associations were found for LAA expression (positive vs. negative) in respect to age and complete remission (CR) rate. Furthermore, the frequency of LAA-positive cases was identical (55%) in both de novo AML (105/190 cases) and sAML (48/88 cases). Monoparametric statistical analysis was also performed individually for each of the six more frequent LAAs. Significant associations (p<0.05) were identified between: (i) CD7 expression and adverse cytogenetics; (ii) CD10 expression and adverse cytogenetics as well as failure to achieve CR, at both cohort level as well as patients \q60 years with de novo AML; and (iii) CD2 expression and shorter overall and disease-free survival (DFS and OS, respectively). Cox-multivariate analysis identified CD2 expression in addition to advanced age, sAML and adverse cytogenetic profile as negative prognostic indicators (p=0.05) for both DFS and OS. In conclusion, expression of LAAs is frequent in AML, among both de novo AML and sAML cases, and significantly associated with adverse cytogenetics. Although the negative prognostic impact of CD2 expression is noteworthy, however, the precise prognostic implications of the expression of individual LAAs are hard to define on single institution retrospective series and will require evaluation in large prospective and well-controlled studies. Disclosures: No relevant conflicts of interest to declare.
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Mansuri, Zeeshan H., Jit H. Brahmbhatt, Roopesh R. Singhal, and Karthik Natarajan. "Altered left atrial appendage function associated with cardioembolic stroke in patients with rheumatic heart disease." International Journal of Advances in Medicine 8, no. 9 (August 21, 2021): 1395. http://dx.doi.org/10.18203/2349-3933.ijam20213243.

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Background: Left atrial appendage (LAA) is usually the first site for thrombus formation in rheumatic heart disease (RHD). LAA function is altered in RHD which may predispose it to thrombus formation. The aim of this study was to determine an association between function of LAA and cardioembolic stroke.Methods:Total 132 patients with RHD were studied by means of transthoracic echocardiography and/or transesophageal echocardiography and left atrial (LA) size, LAA ejection fraction (EF) and peak flow velocities were measured. These patients were followed up for 18 months with reference to development of cardioembolic stroke.Results: Seventy nine patients had atrial fibrillation (AF), of which 34 had thrombus in LAA. Out of 53 patients with sinus rhythm, 5 had LAA thrombus. Mean LAA EF was significantly lower in patients with thrombus in LAA, so was the peak flow velocity (both variables p<0.0001). Saw tooth LAA outflow velocity pattern was visible in 30 (80%) patients with LAA thrombus versus 20 (28%) patients without LAA thrombus. Total 14 patients experienced cardioembolic stroke. Patients with cardioembolic stroke had lower mean LAA EF and peak flow velocity as compared to patients without cardioembolic stroke.Conclusions:Increased LAA size, reduced LAA EF and reduced peak flow velocity are associated with increased risk of cardioembolic stroke. LAA evaluation should be mandatory in deciding treatment strategies in patients with RHD and AF.
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Pourkia, Roghayeh, Mahsa Panahi, Zahra Emkanjoo, Mozhgan Parsaee, Maryam Shojaeifard, Babak Sattartabar, Yousef Rezaei, and Niloufar Samiei. "Morphologic and functional features of left atrial appendage in Iranian population: an echocardiographic study." Journal of Cardiovascular and Thoracic Research 11, no. 3 (August 29, 2019): 230–36. http://dx.doi.org/10.15171/jcvtr.2019.38.

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Introduction: Cardioembolic events are accompanied by left atrial appendage (LAA) in patients suffering from atrial fibrillation (AF); therefore, the LAA closure is implemented as a preventive strategy. The detection of LAA morphologies and function is a paramount step before establishing the LAA closure. Herein, we sought to determine the morphologic features of the LAA in an Iranian population using echocardiographic evaluation. Methods: Seventy-two near-normal heart patients were investigated by conducting a cross-sectional study. All patients were examined using the 2-dimensional and 3-dimensional transesophageal echocardiography (2D- and 3D-TEE) method. The anatomical features and functions of LAA were examined. All images were stored and analyzed offline. Results: The patients’ mean age was 39 ± 15.5 year and 33 (45.8%) were female. The most frequent shape of LAA was wind sock. More LAA lobes was observed in patients with AF compared to those with NSR. In comparison with AF group, the NSR had higher LAA flow velocity (P < 0.01). The paroxysmal AF had greater LAA flow velocity and LAA ejection fraction in comparison with the chronic AF (39 ± 19 vs. 75 ± 22, P < 0.01; and 49±4 vs. 72±14, P < 0.003; respectively). The paroxysmal AF had smaller systolic LAA orifice area in comparison with the chronic AF (P < 0.02). Conclusion: The morphologic features of LAA in Iranian population were within the range of other studies and LAA length and orifice diameters in 2D- and 3D-TEE were consistent. In addition, AF influenced the morphologies and functions of LAA compared to sinus rhythm.
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11

Krivosheev, Y. S., S. Z. Chukov, D. S. Mkrtychev, D. I. Bashta, N. A. Tikhonova, L. I. Vilenskiy, V. N. Kolesnikov, and A. B. Romanov. "View on the left atrial appendage thrombosis on the heart autopsy." Jounal of arrhythmology 27, no. 1 (June 4, 2020): 5–11. http://dx.doi.org/10.35336/va-2020-1-5-11.

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Introduction. Thromboembolic syndrome is a dangerous complication of atrial fibrillation (AF). Left atrial appendage (LAA) is the most frequent location of the thrombus formation in AF. Enlargement of the LAA, special anatomical forms of the appendage are accepted as a risk factors of the LAA thrombosis.Aim: to assess the revealing macro-/microthrombosis LAA in dependence of the morphological form of the appendage in autopsy.Methods. 85 cadaveric hearts were investigated. LAA was measured in three dimensions, the anatomical form of the LAA were estimated by Wang et al. classification. Histological investigation of the LAA slices was made in Hematoxylin Eosin colouring.Results. Macrothrombosis was revealed in 4 LAA. Microthrombus in the LAA were revealed in 46 (54,1%) specimens. We did not find statistical significance between frequency micro thrombosis of the LAA and morphology of the appendage (p = 0,3) with the trend to revealing more microthrombus in anatomic form of the LAA «chicken wing» (65% of this morphological type). Analysis of the diseases died patients showed absence AF in 54,3% cases of the LAA microthrombosis group. AF was diagnosed only in 16 (45,7%) cases in stroke group with revealed micro thrombosis in the LAA.Conclusion. The investigation did not show statistical significance between the anatomical form of LAA and revealing of appendage microthrombosis. Possibly, there is a common pathomorphological process of the LAA thrombosis independence of the AF presence. Further trials are needed to confirm this consumption.
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Hourigan, Christopher Simon, Meghali Goswami, Nawal Alkharouf, Medha Bhagwat, Heidi May Sardon, Ann L. Williams, J. Phillip McCoy, et al. "Systematic analysis of potential targets for immunotherapy in acute myeloid leukemia." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 3104. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.3104.

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3104 Background: The ability to target myeloid malignancies using immunotherapy, without allogeneic transplantation, depends on the capability to target leukemic clones while sparing normal tissues. A variety of putative leukemia associated antigens (LAA) have been identified but an evidence-based list of targets for acute myeloid leukemia (AML) has not yet been established. Methods: De-identified, clinically annotated, samples of peripheral blood and/or bone marrow aspirate from untreated AML patients were collected under IRB-approved protocols from three NCCN cancer centers. Samples were analyzed for commonly observed somatic mutations in ASXL1, DNMT3A, FLT3, IDH1/2, KIT, NPM1, NRAS, RUNX1, TET2, and WT1. Gene expression of 75 consensus LAAs were determined using a custom-designed RT-PCR array. 12 samples underwent extended LAA analysis by flow sorting into “bulk leukemia” and “stem cell enriched” populations. LAA expression was normalized using the geometric mean of three control genes. Results: Samples from 48 AML patients (30 blood, 22 marrow) were suitable for analysis. Average age of patients was 53 (24-86), 50% were female. Cytogenetics were favorable (17%), intermediate (65%) or adverse (19%); 29% presented with a white blood cell count >50,000. Over 10,000 individual data-points were collected. Five distinct patterns of LAA expression were observed in blood from AML patients compared to healthy donors. Conclusions: Understanding the heterogeneity and patterns of AML LAA expression between individuals allows the rational prioritization of potential targets for immunotherapy. Based on our data we predict that targeting any single LAA will likely often be ineffective but that it may be possible to create an inclusive panel of multiple targets with coverage of most AMLs, eliminating the need for individualized personalization of therapy. Such AML antigen signatures may also have utility for minimal residual disease monitoring. [Table: see text]
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Malakouti-Nejad, Bayan B., Eliot J. Winkler, Marjorie I. Johnson, Jorge Catrip, Katie L. Losenno, Bob B. Kiaii, and Michael W. A. Chu. "Complete Obliteration of the Left Atrial Appendage an Analysis of Epicardial Excision and Novel Pericardial Patch Exclusion." Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery 11, no. 4 (July 2016): 282–87. http://dx.doi.org/10.1097/imi.0000000000000281.

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Objective Conventional epicardial excision is believed to be the most effective method of surgically obliterating the left atrial appendage (LAA), although incomplete resection and residual LAA volume may undermine its effectiveness. We sought to compare the impact of conventional epicardial excision with a novel LAA pericardial patch exclusion on residual LAA volume. Methods We performed LAA obliteration using pericardial patch exclusion, followed by conventional epicardial excision, in 27 cadaveric hearts. After each procedure, residual LAA volume was measured by two different techniques and compared with baseline volume. There was no difference in baseline LAA volume between each procedure. Results Procedural success was achieved in all hearts. Conventional epicardial excision left a residual LAA volume of 0.95 mL (24%), as compared with pericardial patch exclusion, which left a residual volume of 0.17 mL (4%, P = 0.0001). Further analysis of fixed and fresh hearts showed that reduction of LAA volume was more pronounced in the fresh hearts, suggesting effectiveness in live patients. Neither technique resulted in any significant change in the endocardial shape of the LAA orifice or injury to the circumflex artery. Conclusions Conventional epicardial excision of the LAA results in significantly more residual LAA volume, which may have important implications in persistent stroke risk. Pericardial patch exclusion seems to achieve near-total elimination of the LAA and may be a superior surgical option.
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Zsarnóczay, Emese, Lili Száraz, Anikó Ilona Nagy, Béla Merkely, Pál Maurovich-Horvat, and Judit Simon. "Left atrial appendage morphology and the risk of stroke." Romanian Journal of Cardiology 31, no. 1 (March 31, 2021): 46–51. http://dx.doi.org/10.47803/rjc.2021.31.1.46.

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In patients with non-valvular atrial fibrillation (AF) the risk of stroke is fi ve times higher than in patients with sinus rhythm. Moreover, stroke is likely to be more severe in the AF patient population. Left atrial appendage (LAA) is the most common source of emboli in AF-related stroke. LAA thrombus is present in 15% of AF patients. Therefore, numerous studies aimed to evaluate the role of LAA structure and function in stroke formation. Higher LAA volume and bigger LAA orifice have been reported to be associated with increased risks of stroke. Moreover, not only the size, but also the shape of the LAA influences thrombus formation. The presence of an obvious bend in the proximal part of the dominant LAA lobe, described as chicken wing LAA morphology has been reported to be protective against stroke. However, other studies are not consistent with this fi nding and there is no consensus about LAA morphology categories. LAA has reservoir, contractile, electric and endocrine functions, that can provide essential information about the risk of clot formation and embolic events. Decreased LAA flow velocity, reflecting lower LAA contractility has been described to be associated with higher stroke risk. All in all, even if the LAA plays an important role in stroke formation, there are controversial literature data, therefore further studies are needed to evaluate the underlying mechanisms.
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Italiano, Gianpiero, Anna Maltagliati, Valentina Mantegazza, Laura Fusini, Maria Elisabetta Mancini, Alessio Gasperetti, Denise Brusoni, et al. "Multimodality Approach for Endovascular Left Atrial Appendage Closure: Head-To-Head Comparison among 2D and 3D Echocardiography, Angiography, and Computer Tomography." Diagnostics 10, no. 12 (December 17, 2020): 1103. http://dx.doi.org/10.3390/diagnostics10121103.

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Background: Percutaneous left atrial appendage closure (LAAC) requires accurate pre- and intraprocedural measurements, and multimodality imaging is an essential tool for guiding the procedure. Two-dimensional (2D TOE) and three-dimensional (3D TOE) transoesophageal echocardiography, cardiac computed tomography (CCT), and conventional cardiac angiography (CCA) are commonly used to evaluate left atrial appendage (LAA) size. However, standardized approaches in measurement methods by different imaging modalities are lacking. The aims of the study were to evaluate the LAA dimension and morphology in patients undergoing LAAC and to compare data obtained by different imaging modalities: 2D and 3D TOE, CCT, and CCA. Methods: A total of 200 patients (mean age 70 ± 8 years, 128 males) were examined by different imaging techniques (161 2D TOE, 103 3D TOE, 98 CCT, and 200 CCA). Patients underwent preoperative CCT and intraoperative 2D and 3D TOE and CCA. Results: A significant correlation was found among all measurements obtained by different modalities. In particular, 3D TOE and CCT measurements were highly correlated with an excellent agreement for the landing zone (LZ) dimensions (LZ diameter: r = 0.87; LAA depth: r = 0.91, p < 0.001). Conclusions: Head-to-head comparison among imaging techniques (2D and 3D TOE, CCT, and CCA) showed a good correlation among LZ diameter measurements obtained by different imaging modalities, which is a parameter of paramount importance for the choice of the LAAC device size. LZ diameters and area by 3D TOE had the best correlation with CCT.
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Shinoda, Koichi, Shogo Hayashi, Daisuke Fukuoka, Ryo Torii, Tsuneo Watanabe, and Takashi Nakano. "Structural Comparison between the Right and Left Atrial Appendages Using Multidetector Computed Tomography." BioMed Research International 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/6492183.

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The three-dimensional (3D) structures of the right atrial appendage (RAA) and left atrial appendage (LAA) were compared to clarify why thrombus formation less frequently occurs in RAA than in LAA. Morphological differences between RAA and LAA of 34 formalin-preserved cadaver hearts were investigated. Molds of RAA and LAA specimens were made and the neck areas, volumes of the atrial appendages (AA), and amount of pectinate muscles (PMs) were analyzed using multidetector computed tomography. In RAA, most PMs were connected to one another and formed a “dendritic” appearance and the inner surface area was smaller than in LAA. RAA had smaller volumes and larger neck areas than LAA. The ratios of the neck area/volume were larger and the amounts of PMs were smaller in RAA than in LAA. The volumes, neck areas, and amount of PMs of RAA were significantly correlated with those of LAA. According to the 3D structure, RAA appears to be suited for a more favorable blood flow, which may explain why the thrombus formation is less common in RAA than in LAA. Examining not only LAA but also RAA by transesophageal echocardiography may be useful in high-risk patients of thrombus formation in LAA because the volume, neck area, and amount of PMs of LAA reflect the shape of RAA.
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Greiner, Jochen, Marlies Götz, Vanessa Schneider, Hubert Schrezenmeier, Markus Wiesneth, Lars Bullinger, Hartmut Döhner, and Susanne Hofmann. "Specific Immune Responses for Leukemia-Associated Antigens Against Myeloid Leukemic Cells Are Increased By Immune Checkpoint Inhibition." Blood 128, no. 22 (December 2, 2016): 4054. http://dx.doi.org/10.1182/blood.v128.22.4054.4054.

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Abstract Immunotherapy in cancer treatment has gained importance in the last few years. The efficacy of immunotherapeutic approaches such as immune-checkpoint inhibitors, chimeric antigen receptor T cells (CARs) or bi-specific T cell activating antibodies becomes more and more obvious. However, mechanisms of these immune responses and responsible antigen structures have to be further elucidated. Leukemia-associated antigens (LAA) represent immunogenic antigens that are candidates for specific immunotherapy since they are target structures relevant for elimination of malignant cells by cytotoxic T cells (CTL). In this work, we investigated the influence of PD-1 antibody Nivolumab and CTLA-4 antibody Ipilimumab on the antigen-specific immune responses by specific T cells against leukemic myeloid blasts in functional T cell assays using ELISpot Assays, tetramer-analysis and colony-forming immunoassays. We investigated T cell responses stimulated against known LAAs like RHAMM, PRAME, WT-1, SSXIP2, Proteinase 3, Survivin, Aurorakinase A and NPM1 against several AML cell lines and samples of AML patients. Expression of different LAAs were measured and correlated to functional T cell assays. Colony forming unit immunoassays displayed a significant inhibition of CFU (colony forming units) in AML patient samples when adding T cells stimulated against various LAA. In all patient samples, effectors activated against at least one LAA were successful to decrease the colony number significantly. The LAAs PRAME, RHAMM and WT1 showed highest frequency and intensity of immunogenic reactions: PRAME stimulated CTL induced an immune response in 83% of tested samples in CFU, stimulated with WT1 in 75% and with RHAMM in 58% of colonies from AML samples. Specific immune responses of cytotoxic T cells were additionally detected by ELISpot assays and correlated to results detected in CFU. Immune effects increased adding nivolumab to the CTL for several days before starting CFU immunoassays whereas no effect was measured when CTL were incubated with Ipilimumab. The combination of Nivolumab and Ipilimumab showed no additional effect of immune responses compared to Nivolumab alone. Taken together, the immune checkpoint inhibitor Nivolumab increases specific T cell responses of LAA-stimulated cytotoxic T cells and the cytotoxic effect of T cells against blasts of AML patients. No additional effect was detected with Ipilimumab. These data suggest that PD-1 antibodies could be an immunotherapeutic approach in AML and combination with LAA-directed vaccination strategies might open interesting application possibilities. Disclosures Greiner: BMS: Research Funding.
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Omran, Heyder. "Cardiac Computed Tomography versus 3D-Transesophageal Echocardiography in Preprocedural Planning of Left Atrial Appendage Closure." Clinical Cardiology and Cardiovascular Interventions 04, no. 06 (March 18, 2021): 01–09. http://dx.doi.org/10.31579/2641-0419/145.

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Aim: Preprocedural imaging of the left atrial appendage (LAA) plays a crucial role in the process of LAA closure (LAAC). This study aimed to compare the influence of preprocedural planning of the LAAC with 3D-transesophageal echocardiography (TEE) and cardiac computed tomography (CCT) versus 3D-TEE alone in patients who underwent LAAC with an Amplatzer Cardiac Plug or Amulet. Materials and Methods: In a retrospective study, 176 patients received a preprocedural 3D-TEE and CCT and 167 patients a 3D-TEE only. Both groups had similar patient characteristics and indications for LAAC. Results: There was no difference in terms of procedural success, procedure time, amount of contrast medium, fluoroscopy time, or radiation dose. Patients with CCT/3D-TEE had a longer hospital stay on average. Besides, there was a different incidence of renal diseases (49% for 3D-TEE versus 27% for CCT/3D-TEE; p < 0.001). The number of periprocedural adverse events was comparable. A device-related thrombus occurred three times in each group, and the peri-device leaks reported were similar. Conclusion: A preprocedural CCT does not decrease major adverse events or improve outcome in patients undergoing LAAC.
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Sylvester, Eric, Mitchell McGovern, An Young Lee, Phanxico Nguyen, Jungeun Park, and Jason B. Benedict. "Partial charge transfer in the salt co-crystal of L-ascorbic acid and 4,4′-bipyridine." Acta Crystallographica Section E Crystallographic Communications 75, no. 6 (May 3, 2019): 728–31. http://dx.doi.org/10.1107/s2056989019005334.

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In the title 1:2 co-crystal, C10H9N2 +·(C6H7.75O6·C6H7.25O6)−, L-ascorbic acid (LAA) and 4,4′-bipyridine (BPy) co-crystallize in the chiral space group P21 with two molecules of LAA, and one molecule of bpy in the asymmetric unit. The structure was modeled in two parts due to possible proton transfer from LAA to the corresponding side of the bpy molecule having an occupancy of approximately 0.25 and part 2 with an occupancy of approximately 0.75. In this structure, LAA forms hydrogen bonds with neighboring LAA molecules, forming extended sheets of LAA molecules which are bridged by bpy molecules. A comparison to a related and previously published co-crystal of LAA and 3-bromo-4-pyridone is presented.
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20

Matko, Sarah, Marcus Odendahl, Martin Bornhaeuser, and Torsten Tonn. "High Prevalence of Functional Laa Specific Cytotoxic T Lymphocytes in Healthy Individuals-Implications for Strategies in Adoptive T Cell Therapies of Relapsed Leukemia." Blood 126, no. 23 (December 3, 2015): 5428. http://dx.doi.org/10.1182/blood.v126.23.5428.5428.

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Abstract While adoptive transfer of virus antigen specific T cells has shown to be effective in therapy of resistant recurrent viremia which is frequently associated with the lack of protective immunity following hematopoietic stem cell transplantation, the transfer of leukemia associated antigen specific (LAA) T cells is less implemented and appears to depend on factors that hamper a successful translation into the clinic. Among them are low frequencies and low antigen affinity of LAA specific T cells which currently mandate laborious in vitro expansion protocols. Moreover, screening of healthy individuals with regard to the presence of LAA specific T cells revealed contradictory results. Since we failed to detect LAA specific T cells in healthy donors using single peptide specificities to known LAA epitopes coupled to MHC Streptamers, here we asked if the use of peptide mixes comprising 15mers overlapping by 11 amino acids and spanning the entire LAA protein could elicit in vitro T cell responses in healthy donors, otherwise undetectable by single peptide staining. A cohort of 48 HLA A*0201 healthy individuals was screened using intracellular cytokine staining (ICS) after stimulation with tumor specific peptide mixes representing well known LAAs (WT1, PRAME, NY-ESO, Survivin and p53). While distinct T-helper cell responses were not observed in either of the specimen tested, cytotoxic T lymphocytes could be elicited and measured after incubation with peptide mixes for 5 hours and subsequent CD8+ IFNγ+ staining in 12 out of 48 healthy subjects. Only one individual displayed specifies against multiple antigens (WT1:0,1%; PRAME:0,5%; NY-ESO:0,1%; p53:0.06%), while the remaining responses were directed to one single antigen per individual. Most prevalent and highest T cell frequencies were found against PRAME in 5 out of all screened subjects (mean 0.4±0.3%; max. 0.8%), followed by WT1 in 4 (mean 0.07±0.03%; max. 0.1%) and NY-ESO in 3 individuals (mean 0,07±0,04%; max. 0,1%); one showed CD8 T cells specific against Survivin (0,03%) and 2 individuals had CD8 frequencies specific against p53 (0,05±0,01; max. 0,06%), respectively. The calculated limit of detection (LOD) for the enumeration of LAA specific T cells was 0,02%. In contrary, testing LAA positive individuals with according MHC Streptamers presenting single peptides of previously described epitopes showed no frequencies exceeding LOD. Further analysis showed LAA specific CD8+ IFNγ+ T cells exhibit mainly a less differentiated phenotype (CD45RA+, CCR7+/-, TNFα+, IL-2+/-) and could be immune-magnetically isolated to purities of 94.5±0.7% using a PRAME-specific IFN-γ capture assay yielding 1*104 antigen specific T cells out of 4*107 PBMCs. Simultaneous enrichment of helper T cells to a purity of 73.0±7.6% proofed their existence, despite no CD4+ response could be detected via ICS in the first place. The cytotoxic potential of the cell product was confirmed in an Europium assay using T2 cells loaded with PRAME peptide mix. The specific lysis accounted to 19.3% at an E:T ratio of 1:1 after 90 minutes of co-incubation. In conclusion, using LAA specific peptide mixes in combination with ICS we were able to show a relatively high prevalence of LAA specific T cells, especially for PRAME, in healthy donors. These LAA specific T cells can be enriched without the need of in vitro expansion culturing ex vivo using the IFN-γ capture assay with regard to achieving a functional LAA specific T cell product for adoptive T cell transfer. Furthermore, a less differentiated phenotype exhibited by a large proportion of LAA specific T cells might contribute to their long term survival in a patient after transplantation. Disclosures No relevant conflicts of interest to declare.
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Melenhorst, J. Joseph, Phillip Scheinberg, Pratip K. Chattopadhyay, Emma Gostick, Kristin Ladell, Mario Roederer, Nancy F. Hensel, Daniel C. Douek, A. John Barrett, and David A. Price. "High avidity myeloid leukemia-associated antigen-specific CD8+ T cells preferentially reside in the bone marrow." Blood 113, no. 10 (March 5, 2009): 2238–44. http://dx.doi.org/10.1182/blood-2008-04-151969.

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Abstract The activity of allogeneic CD8+ T cells specific for leukemia-associated antigens (LAAs) is thought to mediate, at least in part, the curative effects of hematopoietic stem cell transplantation (HSCT) in myeloid malignancies. However, the identity and nature of clinically relevant LAA-specific CD8+ T-cell populations have proven difficult to define. Here, we used a combination of coreceptor-mutated peptide-major histocompatibility complex class I (pMHCI) tetramers and polychromatic flow cytometry to examine the avidity profiles, phenotypic characteristics, and anatomical distribution of HLA A*0201-restricted CD8+ T-cell populations specific for LAAs that are over-expressed in myeloid leukemias. Remarkably, LAA-specific CD8+ T-cell populations, regardless of fine specificity, were confined almost exclusively to the bone marrow; in contrast, CD8+ T-cell populations specific for the HLA A*0201-restricted cytomegalovirus (CMV) pp65495-503 epitope were phenotypically distinct and evenly distributed between bone marrow and peripheral blood. Furthermore, bone marrow-resident LAA-specific CD8+ T cells frequently engaged cognate antigen with high avidity; notably, this was the case in all tested bone marrow samples derived from patients who achieved clinical remission after HSCT. These data suggest that concomitant examination of bone marrow specimens in patients with myeloid leukemias might yield more definitive information in the search for immunologic prognosticators of clinical outcome.
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CHEN, BOR-YANN, YUAN-HAUN LEE, WU-CHING LIN, FENG-HUEI LIN, and KING-FU LIN. "UNDERSTANDING THE CHARACTERISTICS OF L-ASCORBIC ACID-MONTMORILLONITE NANOCOMPOSITE: CHEMICAL STRUCTURE AND BIOTOXICITY." Biomedical Engineering: Applications, Basis and Communications 18, no. 01 (February 25, 2006): 30–36. http://dx.doi.org/10.4015/s1016237206000075.

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Following the previous study to intercalate a 5-fluorouracil (5-FU) into the interlayer spacing of montmorillonite (MMT) for colorectal cancer treatment, we selected a safe and non-pathological microorganism, Saccharomyces cerevisiae, as indicator microorganism to proceed risk assessment on MMT for feasibility study. Dose-response analysis from the perspective in toxicology was conducted to reveal the toxicity rankings of MMT, L-ascorbic acid (LAA) and montmorillonite-L-ascorbic acid (MMT-LAA) composites. This study also tended to intercalate LAA into MMT, observing chemical-structure stabilities of LAA-MMT composites. According to infrared spectroscopic analysis via FTIR, the lattice-vibration peaks of the distorted tetrahedron of SiO4 for MMT were ranged in 400-1200 cm−1. X-ray diffraction analysis also addressed the layer spacing changes in the MMT lattice with pH changes. The variation in the [001] d-spacing changed from 12.4 to 19.4 Å with the increased pH, allowing higher intercalation of viable compounds (e.g., LAA) for controlled-release applications. Compared to MMT, LAA, the lowest toxicity (e.g., EC50=3.77°105 ppm ) of the hybrid MMT-LAA also strongly suggested that MMT-LAA composite is safe to be used for further applications. In contrast, the lowest EC0 (0.564 ppm ) suggested the most sensitive characteristics for MMT-LAA composite to induce the toxic response from no-effect condition. MMT is thus feasible for intercalation of LAA in controlled release to pH changes; particularly, MMT-LAA is considered non-toxic for further applications.
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De Maat, Gijs E., Stefano Benussi, Yoran M. Hummel, Sebastien Krul, Alberto Pozzoli, Antoine H. G. Driessen, Massimo A. Mariani, Isabelle C. Van Gelder, Wim-Jan Van Boven, and Joris R. de Groot. "Surgical Left Atrial Appendage Exclusion Does Not Impair Left Atrial Contraction Function: A Pilot Study." BioMed Research International 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/318901.

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Background. In order to reduce stroke risk, left atrial appendage amputation (LAAA) is widely adopted in recent years. The effect of LAAA on left atrial (LA) function remains unknown. The objective of present study was to assess the effect of LAAA on LA function.Methods. Sixteen patients with paroxysmal AF underwent thoracoscopic, surgical PVI with LAAA (LAAA group), and were retrospectively matched with 16 patients who underwent the same procedure without LAA amputation (non-LAAA group). To objectify LA function, transthoracic echocardiography with 2D Speckle Tracking was performed before surgery and at 12 months follow-up.Results. Mean age was 57 ± 9 years, 84% were male. Baseline characteristics did not differ significantly except for systolic blood pressure (p=0.005). In both groups, the contractile LA function and LA ejection fraction were not significantly reduced. However, the conduit and reservoir function were significantly decreased at follow-up, compared to baseline. The reduction of strain and strain rate was not significantly different between groups.Conclusions. In this retrospective, observational matched group comparison with a convenience sample size of 16 patients, findings suggest that LAAA does not impair the contractile LA function when compared to patients in which the appendage was unaddressed. However, the LA conduit and reservoir function are reduced in both the LAAA and non-LAAA group. Our data suggest that the LAA can be removed without late LA functional consequences.
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Suo, Ya, Zhiwei Zhang, Huaying Fu, Yue Zhang, Meng Yuan, Yuanyuan Wang, Christos A. Goudis, Gary Tse, Tong Liu, and Guangping Li. "Inhibition of renin-angiotensin axis reduces the risk of thrombus formation in the left atrial appendage in patients with hypertension complicated by atrial fibrillation." Journal of the Renin-Angiotensin-Aldosterone System 19, no. 2 (June 2018): 147032031878262. http://dx.doi.org/10.1177/1470320318782623.

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Aims: We examined whether the use of a renin-angiotensin-aldosterone system (RAS) inhibitor plays a role in protecting against left atrial appendage thrombus (LAAT) in patients with hypertension complicated by atrial fibrillation (AF). Methods: Two observational studies were conducted on patients with diagnoses of hypertension and AF, who were categorized into RAS inhibitor user or nonuser groups. Demographic characteristics, clinical characteristics, echocardiographic parameters and hemostatic markers were examined and the occurrence of LAAT during follow-up were recorded. Results: In the first study ( n = 131), LA peak systolic strain and LAA emptying flow velocity (LAA eV) were significantly increased in patients on RAS inhibitors compared with the nonuser group ( p < 0.05). Lower D-dimer and fibrinogen levels were observed in patients on RAS inhibitors ( p < 0.05). In the second study ( n = 99), 25.9% ( n = 11) of patients on RAS inhibitors developed LAAT, compared with 46.7% ( n = 21) in the nonuser group ( p < 0.05). After controlling for risk factors related to LAAT, use of RAS inhibitors remained associated with a significantly lower risk of developing LAAT (HR, 0.406; 95% CI, 0.191–0.862; p = 0.019). Conclusions: RAS inhibitors use was associated with a significant reduction in the risk of LAAT in patients with hypertension and AF.
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Karim, Nabeela, Siew Yen Ho, Edward Nicol, Wei Li, Filip Zemrak, Vias Markides, Vivek Reddy, and Tom Wong. "The left atrial appendage in humans: structure, physiology, and pathogenesis." EP Europace 22, no. 1 (October 3, 2019): 5–18. http://dx.doi.org/10.1093/europace/euz212.

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Abstract For many years, the left atrial appendage (LAA) was considered a dormant embryological remnant; however, it is a structurally complex and functional organ that contributes to cardiac haemodynamic changes and volume homeostasis through both its contractile properties and neurohormonal peptide secretion. When dysfunctional, the LAA contributes to thrombogenesis and subsequent increased predisposition to cardioembolic events. Consequently, the LAA has gained much attention as a therapeutic target to lower this risk. In addition, attention has focused on the LAA in its role as an electrical trigger for atrial tachycardia and atrial fibrillation with ablation of the LAA to achieve electrical isolation showing promising results in the maintenance of sinus rhythm. This in-depth review explores the structure, physiology and pathophysiology of the LAA, as well as LAA intervention and their sequelae.
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26

Caliskan, Etem, Matthias Eberhard, Volkmar Falk, Hatem Alkadhi, and Maximilian Y. Emmert. "Incidence and characteristics of left atrial appendage stumps after device-enabled epicardial closure." Interactive CardioVascular and Thoracic Surgery 29, no. 5 (August 22, 2019): 663–69. http://dx.doi.org/10.1093/icvts/ivz176.

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Abstract OBJECTIVES High success rates for left atrial appendage (LAA) exclusion with the AtriClip (Atricure, USA) device have been reported in the literature. This study evaluated the presence and characteristics of residual LAA stumps after AtriClip LAA exclusion using postoperative short- and long-term computed tomography angiography (CTA). METHODS In this retrospective analysis, 43 of 291 consecutive patients undergoing cardiac surgery with concomitant LAA occlusion using the AtriClip device were identified with available postoperative short- and long-term follow-up by CTA. LAA patency and the absence or the size of a present residual LAA stump were assessed on 2-dimensional multiplanar reconstructions, on maximum intensity projection images and on volume-rendered 3-dimensional computed tomography reconstructions. Based on current recommendations, the threshold for a significant LAA stump length was defined <10 mm. RESULTS The LAA was successfully occluded in all 43 patients (100%) as confirmed by intraoperative transoesophageal echocardiography and CTA imaging with a mean follow-up duration of 7.1 ± 0.8 years post-implant. The absence of blood flow in the excluded LAA was confirmed in all cases. In 31 of 43 patients (72%), no residual stump (0 mm) was observed creating a smooth endocardial surface, CTA revealed residual LAA stumps in 11/43 patients (26%) with a length <10 mm and a significant residual stump with a depth of >10 mm (12 mm) in 1 patient (2%). The mean length, width and depth of the residual stumps were 5.8 ± 2.1, 4.4 ± 1.2 and 7.3 ± 2.3 mm, respectively. CONCLUSIONS This study investigated the incidence of residual stump formation (>10 mm) after LAA closure with the AtriClip device based on CTA imaging data obtained during short- and long-term follow-up. While no LAA stump was detectable in the majority of patients, a non-significant LAA stump (<10 mm) was present in 26% of cases, indicating a favourable LAA occlusion profile for the AtriClip device. However, although a LAA stump length <10 mm is currently considered clinically safe, this definition needs further attention in future studies with regards to its potential clinical implications.
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Abdel Mawla, Tamer, Osama Momtaz, Mohamed Abdel Gayed, and Gomaa Abdelrazek. "Left Atrial Appendage Function Assessment by Tissue Doppler Transesophageal Echocardiography in Acute Ischemic Stroke Patients." Open Access Macedonian Journal of Medical Sciences 9, B (September 7, 2021): 858–64. http://dx.doi.org/10.3889/oamjms.2021.5842.

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Background: Strokes due to Cardioembolic causes are the most severe in ischemic stroke subtypes. LAA flow patterns and function could be assessed accurately by TEE. The study aimed to present the importance of Transesophageal echocardiography in the assessment of LAA function and its relation to cardioembolic stroke. Methods: 120 patients were enrolled in the study and were subdivided into 3 subgroups, each group included 40 patients. Group A; patients had a stroke with normal sinus rhythm, Group B; patients had a stroke with atrial fibrillation, and Group C; normal control subjects. The study participants were evaluated by medical history, physical examination, standard 12-leads electrocardiogram, a transesophageal echocardiographic detailed evaluation of the LAA, and brain CT and/or MRI for patients with stroke. Results: both stroke patients with AF and sinus rhythm had significantly higher LAA mean orifice diameter and higher LAA length than control patients, significantly lower mean LAA medial wall tissue Doppler upward and downward motion velocities than control patients and that patients with stroke and AF had significantly lower mean LAA pulsed wave emptying and filling velocities than both patients with stroke and sinus rhythm and control patients. Presence of LAA thrombi, spontaneous echo contrast, and stroke recurrence were higher in stroked AF patients than stroke patients with sinus rhythm. Conclusion: increased LAA orifice diameter, LAA length, and reduced filling and emptying velocities and upward and downward motion velocities of the medial wall of LAA as detected by TEE are associated with stroke and cardio embolization.
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Vivoli, Giorgia, Emanuele Gasparotti, Marco Rezzaghi, Elisa Cerone, Massimiliano Mariani, Luigi Landini, Sergio Berti, Vincenzo Positano, and Simona Celi. "Simultaneous Functional and Morphological Assessment of Left Atrial Appendage by 3D Virtual Models." Journal of Healthcare Engineering 2019 (May 21, 2019): 1–8. http://dx.doi.org/10.1155/2019/7095845.

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Purpose. The left atrial appendage (LAA) is responsible for thrombus formation in patients with atrial fibrillation. The evaluation of both LAA function and morphology is crucial for the patient characterization and the preprocedural planning of LAA closure intervention. Despite the availability of 3D imaging modalities, the current standard image analysis is based on manual delineation of the LAA contours on 2D views. Methods. In this study, a comprehensive approach based on a full 3D analysis of the tomographic dataset by surface extraction and processing (3D-S) is presented. The proposed method allows extracting functional and morphologic information in the entire cardiac cycle by minimalizing manual user interaction. The proposed methodology has been validated on ten computer tomography datasets. Results. The proposed 3D-S method was feasible in all cases. Reproducibility was improved with respect to the reference 2D manual procedure (2D-S) (coefficient of variation 2.9 vs. 4.1% for diastolic ostium area; 3.8 vs. 6.1% for systolic ostium area; 2.4 vs. 5.3% for diastolic LAA volume; 2.7 vs. 5.9% for systolic LAA volume; and 7.7 vs. 17.1% for LAA ejection fraction). No significant differences were found between 2D-S and 3D-S measurements. Conclusions. In this study, we introduced a fully 3D approach for LAA characterization, allowing the simultaneous assessment of LAA function and geometry. The proposed approach could be used to improve the patient selection and the best sizing of the device for LAA closure and to allow a patient-specific 3D printing.
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Lee, Yuan-Haun, Bor-Yann Chen, and Chi-Yu Chang. "ASSESSMENT UPON CHARACTERISTICS OF CONSTRUCTED L-ASCORBIC ACID/MONTMORILLONITE COMPOSITE." Biomedical Engineering: Applications, Basis and Communications 19, no. 03 (June 2007): 145–55. http://dx.doi.org/10.4015/s1016237207000185.

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This study constructs new L-ascorbic acid (LAA) composites in low toxicity and high stability for feasible application. Although literature reveals that sodium thiosulphate could stabilize the activity of LAA, our findings show that the significant toxicity was provoked by sodium thiosulphate. A safe and non-toxic material montmorillonite (MMT) was thus used to attenuate this toxicity and to sustain the stability of composites with economic feasibility for practical use. As the proton released from LAA promots the increases of interlayer spacing of clay layers in MMT, the formation of stable and safe LAA composites resulted. The most feasible were found to be the composites [ MMT + 10% LAA + 0.90% Na 2 S 2 O 3] and [ MMT + 5% LAA + 1.35% Na 2 S 2 O 3].
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30

Asai, S., R. Ohta, M. Shirota, G. Watanabe, and K. Taya. "Differential responses of the hypothalamo-pituitary-adrenocortical axis to acute restraint stress in Hatano high- and low-avoidance rats." Journal of Endocrinology 181, no. 3 (June 1, 2004): 515–20. http://dx.doi.org/10.1677/joe.0.1810515.

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The high- and low-avoidance animal (HAA and LAA respectively) strains of Hatano rats were originally selected and bred from Sprague-Dawley rats for their performance in the shuttle-box task. The present study focused on the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis of HAA and LAA rats in response to restraint stress. The restraint stress induced an elevation in plasma concentrations of ACTH, prolactin, corticosterone and progesterone. Peak levels of plasma ACTH during stress conditions were significantly higher in HAA rats than in LAA rats, while peak levels of prolactin were significantly lower in HAA rats than in LAA rats. Under stress conditions, ACTH and prolactin synthesis in the anterior pituitary glands was significantly higher in HAA rats compared with LAA rats. The peak plasma concentrations of corticosterone, during restraint stress, were significantly higher in LAA rats compared with HAA rats. These results indicate that the response of the hypothalamo-pituitary axis to acute restraint stress is greater in HAA rats than in LAA rats, whereas the ACTH-induced adrenal response of corticosterone release is higher in LAA rats than in HAA rats. On the other hand, prolactin secretory activity is higher in LAA rats compared with HAA rats. These differences in endocrine responses to stress may be involved in the regulation of the avoidance responses in the shuttle-box task.
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Takahashi, Mamoru, Gen Yamada, Hiroyuki Koba, and Hiroki Takahashi. "Computed Tomography-Based Centrilobular Emphysema Subtypes Relate with Pulmonary Function." Open Respiratory Medicine Journal 7, no. 1 (June 14, 2013): 54–59. http://dx.doi.org/10.2174/1874306401307010054.

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Introduction: Centrilobular emphysema (CLE) is recognized as low attenuation areas (LAA) with centrilobular pattern on high-resolution computed tomography (CT). However, several shapes of LAA are observed. Our preliminary study showed three types of LAA in CLE by CT-pathologic correlations. This study was performed to investigate whether the morphological features of LAA affect pulmonary functions. Materials and Methods: A total of 73 Japanese patients with stable CLE (63 males, 10 females) were evaluated visually by CT and classified into three subtypes based on the morphology of LAA including shape and sharpness of border; patients with CLE who shows round or oval LAA with well-defined border (Subtype A), polygonal or irregular-shaped LAA with ill-defined border (Subtype B), and irregular-shaped LAA with ill-defined border coalesced with each other (Subtype C). CT score, pulmonary function test and smoking index were compared among three subtypes. Results: Twenty (27%), 45 (62%) and 8 cases (11%) of the patients were grouped into Subtype A, Subtype B and Subtype C, respectively. In CT score and smoking index, both Subtype B and Subtype C were significantly higher than Subtype A. In FEV1%, Subtype C was significantly lower than both Subtype A and Subtype B. In diffusing capacity of lung for carbon monoxide, Subtype B was significantly lower than Subtype A. Conclusion: The morphological differences of LAA may relate with an airflow limitation and alveolar diffusing capacity. To assess morphological features of LAA may be helpful for the expectation of respiratory function.
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Tilz, Roland Richard, Thomas Fink, Krzysztof Bartus, Tom Wong, Julia Vogler, Karin Nentwich, Sandeep Panniker, et al. "A collective European experience with left atrial appendage suture ligation using the LARIAT+ device." EP Europace 22, no. 6 (February 11, 2020): 924–31. http://dx.doi.org/10.1093/europace/euaa004.

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Abstract Aims We report the collective European experience of percutaneous left atrial appendage (LAA) suture ligation using the recent generation LARIAT+ suture delivery device. Methods and results A total of 141 patients with non-valvular atrial fibrillation and contraindication to oral anticoagulation (OAC), thrombo-embolic events despite OAC or electrical LAA isolation were enrolled at seven European hospitals to undergo LAA ligation. Patients were followed up by clinical visits and transoesophageal echocardiography (TOE) following LAA closure. Left atrial appendage ligation was completed in 138/141 patients (97.8%). Three patients did not undergo attempted deployment of the LARIAT device due to pericardial adhesion after previous epicardial ventricular tachycardia ablation (n = 1), a pericardial access-related complication (n = 1), and multiple posterior LAA lobes (n = 1). Serious 30-day procedural adverse events occurred in 4/141 patients (2.8%). There were two device-related LAA perforations (1.4%) not resulting in any corrective intervention as the LAA was completely sealed with the LARIAT. Minor adverse events occurred in 19 patients (13.5%), including two pericardial effusions due to procedure-related pericarditis requiring pericardiocentesis. Transoesophageal echocardiography was performed after LAA ligation in 103/138 patients (74.6%) after a mean of 181 ± 72 days. Complete LAA closure was documented in 100 patients (97.1%). Two patients (1.8% of patients with follow-up) experienced a transient ischaemic attack at 4 and 7 months follow-up, although there was no leak observed with TOE. There were two deaths during long-term follow-up which were both not device related. Conclusion Initial experience with the LARIAT+ device demonstrates feasibility of LAA exclusion. Further larger prospective studies with longer follow-up are warranted.
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Senadeera, Sajith C., David G. Palmer, Ross Keenan, James Beharry, Jen Yuh Lim, Michael A. Hurrell, Paul Mouthaan, et al. "Left Atrial Appendage Thrombus Detected During Hyperacute Stroke Imaging Is Associated With Atrial Fibrillation." Stroke 51, no. 12 (December 2020): 3760–64. http://dx.doi.org/10.1161/strokeaha.120.030258.

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Background and Purpose: Left atrial appendage (LAA) is the likely embolic source in atrial fibrillation (AF)–related cardioembolic strokes. We sought to determine the prevalence of LAA thrombus on hyperacute stroke imaging and its association with AF. Methods: We retrospectively examined the clinical and radiological features of patients assessed through the hyperacute stroke imaging pathway over a 12-month period at Christchurch Hospital. The LAA was included in the computed tomography angiogram scan-range as part of the multimodal imaging protocol. Two radiological readers blinded to clinical information independently assessed for the presence of LAA thrombus. The association between AF and LAA thrombus was determined by multivariable logistic regression analysis. Results: Of 303 patients included in the analysis, the overall prevalence of LAA thrombus was 6.6% and 14.9% in patients with known AF. Patients with LAA thrombus were older (85 versus 75 years, P <0.01), more commonly had known or newly diagnosed AF (75% versus 30%, P <0.01) and heart failure (30% versus 8%, P =0.01), and was associated with intracranial large vessel occlusion (65% versus 39%, P =0.02). In the multivariable model, AF (odds ratio, 3.71 [95% CI, 1.25–11.01] P =0.02) was independently associated with LAA thrombus after adjusting for age and congestive heart failure. Interrater reliability was moderate (kappa=0.56). Conclusions: LAA thrombus is a potential radiological marker of AF and can be assessed as a part of hyperacute stroke imaging.
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Jang, Sun-Joo, S. Chiu Wong, and Bobak Mosadegh. "Leaks after Left Atrial Appendage Closure: Ignored or Neglected?" Cardiology 146, no. 3 (2021): 384–91. http://dx.doi.org/10.1159/000513901.

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Left atrial appendage (LAA) closure has recently been approved as an alternative management for stroke prevention in patients with chronic atrial fibrillation who have difficulties with long-term oral anticoagulation. The various shapes and sizes of LAA and orientation of the atrial ostium may contribute to the incomplete LAA closure from circular design devices and orientation of the non-steerable delivery catheter. Incomplete closure of LAA leads to a high-velocity blood flow through the peri-device gap, resulting in peri-device leak (PDL). Residual leaks are frequently diagnosed after LAA closure procedures, regardless of closure methods. There is a controversy in the clinical significance of the leaks, particularly about its association with thromboembolic events. PDL &#x3c;5 mm was not associated with any increase of risk for thromboembolism. Current literatures with small study population have not been sufficient to clarify the role of the leaks after LAA closure. Nevertheless, management of severe leaks has been a challenging concern for cardiologists. Leaks after epicardial LAA closures are at the neck of the incompletely closed LAA and have shown to increase the risk of thromboembolism. Percutaneous closure of the leaks after LAA closure has been attempted with good safety and success, but long-term safety and efficacy remains unclear. Further large long-term studies which aim to assess the role of leaks or PDLs in predicting thromboembolic events and management strategies are warranted.
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Palios, John, and Ioannis Paraskevaidis. "Thromboembolism Prevention via Transcatheter Left Atrial Appendage Closure with Transeosophageal Echocardiography Guidance." Thrombosis 2014 (February 11, 2014): 1–6. http://dx.doi.org/10.1155/2014/832752.

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Atrial fibrillation (AF) is an independent risk factor for stroke. Anticoagulation therapy has a risk of intracerebral hemorrhage. The use of percutaneous left atrial appendage (LAA) closure devices is an alternative to anticoagulation therapy. Echocardiography has a leading role in LAA closure procedure in patient selection, during the procedure and during followup. A comprehensive echocardiography study is necessary preprocedural in order to identify all the lobes of the LAA, evaluate the size of the LAA ostium, look for thrombus or spontaneous echo contrast, and evaluate atrial anatomy, including atrial septal defect and patent foramen ovale. Echocardiography is used to identify potential cardiac sources of embolism, such as atrial septal aneurysm, mitral valve disease, and aortic debris. During the LAA occlusion procedure transeosophageal echocardiography provides guidance for the transeptal puncture and monitoring during the release of the closure device. Procedure-related complications can be evaluated and acceptable device release criteria such as proper position and seating of the occluder in the LAA, compression, and stability can be assessed. Postprocedural echocardiography is used for followup to assess the closure of the LAA ostium. This overview paper describes the emerging role of LAA occlusion procedure with transeosophageal echocardiography guidance as an alternative to anticoagulation therapy in patients with AF.
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Othman, Nurhanisah, Mas Masarudin, Cha Kuen, Nurul Dasuan, Luqman Abdullah, and Siti Md. Jamil. "Synthesis and Optimization of Chitosan Nanoparticles Loaded with L-Ascorbic Acid and Thymoquinone." Nanomaterials 8, no. 11 (November 7, 2018): 920. http://dx.doi.org/10.3390/nano8110920.

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The combination of compounds with different classes (hydrophobic and hydrophilic characters) in single chitosan carrier is a challenge due to the hydrophilicity of chitosan. Utilization of l-ascorbic acid (LAA) and thymoquinone (TQ) compounds as effective antioxidants is marred by poor bioavailability and uptake. Nanoparticles (NPs) solved the problem by functioning as a carrier for them because they have high surface areas for more efficient delivery and uptake by cells. This research, therefore, synthesized chitosan NPs (CNPs) containing LAA and TQ, CNP-LAA-TQ via ionic gelation routes as the preparation is non-toxic. They were characterized using electron microscopy, zetasizer, UV–VIS spectrophotometry, and infrared spectroscopy. The optimum CNP-LAA-TQ size produced was 141.5 ± 7.8 nm, with a polydispersity index (PDI) of 0.207 ± 0.013. The encapsulation efficiency of CNP-LAA-TQ was 22.8 ± 3.2% for LAA and 35.6 ± 3.6% for TQ. Combined hydrophilic LAA and hydrophobic TQ proved that a myriad of highly efficacious compounds with poor systemic uptake could be encapsulated together in NP systems to increase their pharmaceutical efficiency, indirectly contributing to the advancement of medical and pharmaceutical sectors.
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Tokunaga, Keisuke, Go Hashimoto, Tadataka Mizoguchi, Kota Mori, Masahiro Shijo, Juro Jinnouchi, Takahiro Kuwashiro, Masahiro Yasaka, Takanari Kitazono, and Yasushi Okada. "Left Atrial Appendage Flow Velocity and Multiple Infarcts in Cryptogenic Stroke." Cerebrovascular Diseases 50, no. 4 (2021): 429–34. http://dx.doi.org/10.1159/000514672.

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<b><i>Background:</i></b> To validate the hypothesis that cryptogenic stroke with multiple infarcts included embolic stroke due to left atrial appendage (LAA) dysfunction, the present retrospective observational study was aimed to clarify the association between LAA flow velocity (LAA-FV) and multiple infarcts in patients with cryptogenic stroke. <b><i>Methods:</i></b> From consecutive patients with cryptogenic stroke admitted to our hospital within 7 days after onset, patients without brain magnetic resonance imaging (MRI) on admission or without transesophageal echocardiography (TEE) during acute hospitalization were excluded, and the remaining patients were enrolled. Multiplicity of fresh infarcts was assessed using diffusion-weighted images from brain MRI. LAA-FV was defined as LAA peak emptying flow velocity on TEE. <b><i>Results:</i></b> Of 786 enrolled patients, 522 patients (66%) had a single infarct, and the remaining 264 patients (34%) had multiple infarcts. The percentage of multiple infarcts decreased with increasing quartiles of LAA-FV (<i>p</i> for trend &#x3c;0.001). The adjusted odds ratio for multiple infarcts decreased with increasing quartiles of LAA-FV (adjusted odds ratio in the fourth quartile, 0.39; 95% confidence interval, 0.25–0.60; compared with the first quartile). LAA-FV as a continuous variable was negatively associated with multiple infarcts (adjusted odds ratio per 10 cm/s, 0.87; 95% confidence interval, 0.81–0.92). <b><i>Conclusions:</i></b> Reduced LAA-FV on TEE was associated with multiple infarcts in patients with cryptogenic stroke. The present findings indicate that cryptogenic stroke with multiple infarcts includes embolic stroke due to LAA dysfunction.
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Hill, Arthur C., and T. Sloane Guy. "Minimally Invasive Surgical Implantation of the Percutaneous Left Atrial Appendage Transcatheter Occlusion Device Initial Experience in a Canine Model." Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery 7, no. 1 (January 2012): 52–58. http://dx.doi.org/10.1097/imi.0b013e3182551936.

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Objective Atrial fibrillation (AF) is a significant cause of thromboembolism and stroke. Left atrial appendage (LAA) occlusion is associated with a decreased risk of stroke in patients with AF. Percutaneous implantation of the percutaneous LAA transcatheter occlusion (PLAATO) device has shown reduction in stroke risk and decreased need for anticoagulation. A surgical method of PLAATO implantation is proposed for its utility and efficacy in cardiac surgical procedures, where LAA occlusion is indicated as a primary procedure or as an adjunct. We describe a surgical method for PLAATO deployment in an experimental model that simulates various operative scenarios including right minithoracotomy, right video-assisted thoracoscopic, or median sternotomy. Methods The PLAATO LAA occlusion device was deployed into the LAA in six dogs using a right minithoracotomy incision and catheter deployment via direct left atrial access. Intracardiac echocardiography and left atrial angiography were used to size, position, and verify proper deployment of the device. Results Successful PLAATO deployment was achieved in six of the six dogs. One dog required replacement of an undersized device. One dog required replacement of an oversized device. Four dogs required minor repositioning for optimal positioning. Complete flush occlusion of the LAA was achieved in three dogs; the other three dogs had trace leak by LAA angiography. Conclusions Experimental surgical implantation of the PLAATO device produces stable and complete occlusion of the LAA. Potential surgical indications for PLAATO implantation include patients with AF where a percutaneous approach to LAA occlusion is contraindicated or in patients with AF who require concurrent cardiac surgery.
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Franciulli, Marco, Giuseppe De Martino, Mariateresa Librera, Ahmed Desoky, Antonio Mariniello, Annarita Iavazzo, Fabio Scigliano, Giampiero Esposito, and Luigi Chiariello. "Stand-Alone Thoracoscopic Left Atrial Appendage Closure in Nonvalvular Atrial Fibrillation Patients at High Bleeding Risk." Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery 15, no. 6 (October 13, 2020): 541–46. http://dx.doi.org/10.1177/1556984520960116.

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Objective In nonvalvular atrial fibrillation (AF) patients at high bleeding risk, oral anticoagulants (OAC) may be contraindicated, and percutaneous left atrial appendage (LAA) closure has been advocated. However, following percutaneous procedure, either OAC or dual antiplatelet treatment is required. In this study, we present our experience in treating nonvalvular AF patients at high bleeding risk with thoracoscopic LAA closure with no subsequent antithrombotic therapy. Methods From April 2019 to January 2020, 20 consecutive AF patients, mean age 75.1 years, 16 (80%) males, underwent thoracoscopic LAA closure as a stand-alone procedure, using an epicardial clip device. OAC and antiplatelet therapy were contraindicated. Mean CHA2DS2-VASc score was 3.61, and the mean HAS-BLED score was 4.42. Successful LAA closure was assessed by transesophageal echocardiography. Primary endpoints were complete LAA closure (no residual LAA flow), operative complications, and all-cause mortality; secondary endpoints were 30-day and 6-month complications (death, ischemic stroke, hemorrhagic stroke, transient ischemic attack, any bleeding). Mean follow-up was 6 ± 4 months. Results Complete LAA closure was achieved in all patients. No operative clip-related complications or deaths occurred. At follow-up, freedom from postoperative complications was 95% and from any cerebrovascular events was 100%. Overall survival rate was 100%. Conclusions In nonvalvular AF patients at high bleeding risk (HAS-BLED score >3), thoracoscopic LAA closure appears to be a valid alternative to percutaneous techniques not requiring dual antiplatelet or OAC treatment. Apparently, external LAA clipping minimizes the risk of thromboembolic events as compared with percutaneous procedures.
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Crijns, Harry J., Stefan G. Spitzer, and Claudio Tondo. "Targeting Atrial Fibrillation Patients for Left Atrial Appendage Occlusion with Epicardial Closing Devices." European Journal of Arrhythmia & Electrophysiology 4, no. 2 (2018): 53. http://dx.doi.org/10.17925/ejae.2018.4.2.53.

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The left atrial appendage (LAA) is a key source of thrombi in patients with non-valvular atrial fibrillation (AF) and a major clinical focus for stroke prevention. Current surgical exclusion remains suboptimal and percutaneous approaches targeting the LAA, although well validated, fail to offer complete and durable occlusion for all patients. The high anatomical variability of the LAA demands a more tailored and targeted treatment approach. Epicardial LAA clip occlusion represents an important alternative approach for patients with AF not amenable to catheter closure or where anticoagulation is contraindicated. In this article, we briefly review the clinical evidence for epicardial devices in LAA occlusion, with a focus on the AtriClip and discuss their role in stroke prevention strategies.
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Othman, Nurhanisah, Siti Nurul Ain Md. Jamil, Mas Jaffri Masarudin, Luqman Chuah Abdullah, Rusli Daik, and Nor Syazwani Sarman. "l-Ascorbic Acid and Thymoquinone Dual-Loaded Palmitoyl-Chitosan Nanoparticles: Improved Preparation Method, Encapsulation and Release Efficiency." Processes 8, no. 9 (August 26, 2020): 1040. http://dx.doi.org/10.3390/pr8091040.

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Encapsulation of dual compounds of different characters (hydrophilic and hydrophobic) in single nanoparticles carrier could reach the site of action more accurately with the synergistic effect but it is less investigated. In our previous findings, combined-compounds encapsulation and delivery from chitosan nanoparticles were impaired by the hydrophilicity of chitosan. Therefore, hydrophobic modification on chitosan with palmitic acid was conducted in this study to provide an amphiphilic environment for better encapsulation of antioxidants; hydrophobic thymoquinone (TQ) and hydrophilic l-ascorbic acid (LAA). Palmitoyl chitosan nanoparticles (PCNPs) co-loaded with TQ and LAA (PCNP-TQ-LAA) were synthesized via the ionic gelation method. Few characterizations were conducted involving nanosizer, Fourier-transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HRTEM). UV–VIS spectrophotometry was used to analyze the encapsulation and release efficiency of the compounds in PCNPs. Successfully modified PCNP-TQ-LAA had an average particle size of 247.7 ± 24.0 nm, polydispersity index (PDI) of 0.348 ± 0.043 and zeta potential of 19.60 ± 1.27 mV. Encapsulation efficiency of TQ and LAA in PCNP-TQ-LAA increased to 64.9 ± 5.3% and 90.0 ± 0%, respectively. TQ and LAA in PCNP-TQ-LAA system showed zero-order release kinetics, with a release percentage of 97.5% and 36.1%, respectively. Improved preparation method, encapsulation and release efficiency in this study are anticipated to be beneficial for polymeric nanocarrier development.
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Wang, Yu, Mingqi Li, Lishan Zhong, Siqi Ren, Hezhi Li, Yongwen Tang, Zhilian Li, and Hongwen Fei. "Left Atrial Strain as Evaluated by Two-Dimensional Speckle Tracking Predicts Left Atrial Appendage Dysfunction in Chinese Patients with Atrial Fibrillation." Cardiology Research and Practice 2020 (March 21, 2020): 1–8. http://dx.doi.org/10.1155/2020/5867617.

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Left atrial appendage (LAA) dysfunction identified by transesophageal echocardiography (TEE) is a powerful predictor of stroke in patients with atrial fibrillation (AF). The aim of our study is to assess if there is a correlation between the left atrial (LA) functional parameter and LAA dysfunction in the AF patients. This cross-sectional study included a total of 249 Chinese AF patients who did not have cardiac valvular diseases and were undergoing cardiac ablation. TEE was performed in all the patients who were categorized into two groups according to their left atrial appendage (LAA) function. A total of 120 of the 249 AF patients had LAA dysfunction. Univariate and multivariate logistic regression was conducted to assess the independent factors that correlated with the LAA dysfunction. Different predictive models for the LAA dysfunction were compared with the receiver operating characteristic (ROC) curve. The final ROC curve on the development and validation datasets was drawn based on the calculation of each area under the curves (AUC). Univariate and multivariate analysis showed that the peak left atrial strain (PLAS) was the most significant factor that correlated with the LAA dysfunction. PLAS did not show inferiority amongst all the models and revealed strong discrimination ability on both the development and validation datasets with AUC 0.818 and 0.817. Our study showed that a decrease in PLAS is independently associated with LAA dysfunction in the AF patients.
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Vecherskiy, Yu Yu, Yu I. Bogdanov, R. E. Batalov, V. V. Zatolokin, V. V. Saushkin, K. V. Zavadovskiy, and S. V. Popov. "A new method of left atrial appendage occlusion for the prevention of thromboembolic complications in patients with atrial fibrillation during coronary artery bypass grafting." Russian Journal of Cardiology 25, no. 8 (September 14, 2020): 3699. http://dx.doi.org/10.15829/1560-4071-2020-3699.

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Aim. To optimize the surgical technique for left atrial appendage (LAA) occlusion in patients with atrial fibrillation (AF) during coronary artery bypass grafting.Material and methods. The study included 60 patients with atrial fibrillation (AF). The patients were randomly divided into 2 groups. In the first group of patients, LAA was closed using the developed two-suture technique. In patients of the second group, a purse string suture was applied to the LAA. All patients underwent transesophageal echocardiography (TEE) before surgery to rule out the presence of intracardiac blood clots. To assess the effectiveness of the method in the postoperative period, TEE was performed.Results. According to postoperative TEE, one case of LAA recanalization in each group was revealed (p>0,05). In the second group, the residual LAA cavity after applying a purse string suture was revealed. During the follow-up period, there were no neurological complications and deaths.Conclusion. According to the study results, it was found that the proposed two-suture technique for LAA occlusion is not less effective than the purse-string suture. The developed technique of two-suture epicardial occlusion of LAA showed actual technical advantages, allowing to optimize this surgery in different categories of patients.
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Ряшенцев, Дмитрий Сергеевич, and Евгений Анатольевич Беленков. "INVESTIGATION OF NEW POLYMORPHIC VARIETIES OF BORON NITRIDE WITH DIAMOND-LIKE STRUCTURES." Physical and Chemical Aspects of the Study of Clusters, Nanostructures and Nanomaterials, no. 12() (December 15, 2020): 493–503. http://dx.doi.org/10.26456/pcascnn/2020.12.493.

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В работе проведено теоретическое исследование новых полиморфных разновидностей нитрида бора, имеющих алмазоподобные структуры. В результате расчетов методом теории функционала плотности в градиентном приближении была установлена возможность устойчивого существования четырех новых структурных разновидностей нитрида бора: BN - LA4, BN - LA5, BN - LA6 и BN - LA7 . Энергия сублимации новых BN фаз варьируется в диапазоне от 16,85 до 17,84 эВ/(BN), ширина запрещенной зоны - от 4,34 до 6,07 эВ. Объемная плотность BN полиморфов изменяется от 3,020 до 3,452 г/см. The article presents a theoretical study of new polymorphic varieties of boron nitride with diamond-like structures. As a result of calculations by the density functional theory method in the gradient approximation, the possibility of stable existence of four new structural varieties of boron nitride: BN - LA4, BN - LA5 , BN - LA6, and BN - LA7 was established. The sublimation energy of new BN phases varies in the range from 16,85 to 17,84 eV/(BN), the band gap is from 4,34 to 6,07 eV. The bulk density of BN polymorphs varies from 3,020 to 3,452 g/cm.
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Sakamoto, I., K. Hayashi, N. Matsunaga, Y. Ogawa, Y. Matsuoka, T. Okimoto, M. Takagi, K. Yano, G. Toda, and Y. Miyahara. "Coronary Angiographic Finding of Thrombus in the Left Atrial Appendage." Acta Radiologica 37, no. 3P2 (May 1996): 749–53. http://dx.doi.org/10.1177/02841851960373p264.

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Purpose: The value of coronary angiography in the diagnosis of thrombus in the left atrial appendage (LAA) was retrospectively analyzed. Material and Methods: The study covers 34 patients in whom coronary angiography showed coronary neovascularity in LAA with coronary artery-left atrial fistula indicating LAA thrombus. All 34 patients underwent transthoracic echocardiography within one week of coronary angiography. Open-heart surgery was undertaken 2–31 months after angiography in 28 patients. Results: Coronary neovascularity and coronary artery-left atrial fistula arose from the left circumflex artery in 28 patients, and from the left circumflex artery and the right coronary artery in the remaining 6 patients. By echocardiography, LAA thrombus was detected in only one of the 34 patients. In 18 of the 28 patients who underwent open-heart surgery, LAA thrombus was found at surgery to have resolved. Conclusion: Coronary angiography is useful in the diagnosis of LAA thrombus, and coronary neovascularity and fistula formation may indicate that the thrombus can spontaneously resolve.
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Miyashita, S., Y. Inaba, T. Somfai, M. Geshi, T. Nagai, H. Koyama, and O. Dochi. "165 THE EFFECTS OF L-CARNITINE AND LINOLEIC ACID ALBUMIN SUPPLEMENTATION ON THE DEVELOPMENT AND CRYOSURVIVAL OF BOVINE IN VITRO-MATURED/IN VITRO-FERTILIZED EMBRYOS IN IN VITRO CULTURE MEDIUM." Reproduction, Fertility and Development 24, no. 1 (2012): 194. http://dx.doi.org/10.1071/rdv24n1ab165.

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The objective of this study was to investigate the effects of the supplementation of a lipid metabolism inducer, L-carnitine (LC) and a membrane stabilizer, linoleic acid albumin (LAA), on the developmental competence and cryosurvival of bovine in vitro-matured/in vitro-fertilized embryos in in vitro culture medium. Cumulus–oocyte complexes collected from the ovaries of slaughtered cattle were matured for 20 h in TCM-199 supplemented with 5% calf serum (CS) and 0.02 AU mL–1 of FSH at 38.5°C in an atmosphere of 5% CO2 in air. After IVF (Day 0), presumptive zygotes were cultured in CRlaa containing 5% CS at 38.5°C in an atmosphere of 5% CO2, 5% O2 and 90% N2 for 9 days. The culture medium was supplemented with 0.6 mg mL–1 of LC (LC group; n = 180) or with 0.25 mg mL–1 of LAA (LAA group; n = 180) or with both LC and LAA (LC + LAA group; n = 180) or without LC and LAA (control; n = 178). The cleavage rates were recorded on Day 2 and the blastocyst formation rates were recorded on Day 7 to 9. Expanded blastocysts harvested on Day 7 and 8 (LAA group: n = 31; LC group: n = 29; LC + LAA group: n = 25; control group: n = 33) were used for freezing in modified PBS supplemented with 1.5 M ethylene glycol, 0.1 M sucrose and 20% CS. After thawing, they were cultured in TCM-199 supplemented with 20% FBS and 0.1 mM β-mercaptoethanol at 38.5°C under 5% CO2 in air for 72 h. The rates of re-expansion, hatching and formation of hatched blastocysts were determined at 24, 48 and 72 h after thawing, respectively. The rates of cleavage and blastocyst formation were expressed as mean ± s.e.m. and analysed by ANOVA. The post-thaw survival rates of frozen embryos were analysed by chi-square test. The cleavage rate in the control group (69.1 ± 2.5%) was significantly lower than that in the LAA (81.8 ± 3.8%) and LC + LAA groups (77.9 ± 1.4%) but did not differ from that in the LC group (73.8 ± 2.4%). The blastocyst formation rate in the control group (21.7 ± 2.8%) was significantly lower (P < 0.05) than those in the LAA and LC + LAA groups (33.5 ± 2.8% and 31.4 ± 2.4%, respectively), but it did not differ significantly from that of the LC group (32.1 ± 3.3%) despite a strong tendency (P = 0.06). There were no significant differences among the control, LC, LAA and the LC + LAA groups in post-thaw re-expansion rates (66.7, 75.9, 67.7 and 76.0%, respectively), hatching rates (48.5, 69.0, 58.1 and 64.0%, respectively) and rates of formation of hatched blastocysts (51.5, 62.1, 61.3 and 64.0%, respectively). These results indicate that the addition of LC and LAA to the medium for in vitro culture of in vitro-matured/in vitro-fertilized bovine embryos improved their ability to develop to the blastocyst stage; however, the effects on the freezing tolerance were not verified.
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Yeow, Wen-Loong, and Saibal Kar. "Device- and LAA-Specific Characteristics for Successful LAA Closure." Interventional Cardiology Clinics 3, no. 2 (April 2014): 239–54. http://dx.doi.org/10.1016/j.iccl.2013.12.002.

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Han, Frederick T., Krzysztof Bartus, Dhanunjaya Lakkireddy, Francia Rojas, Jacek Bednarek, Boguslaw Kapelak, Magdalena Bartus, et al. "The effects of LAA ligation on LAA electrical activity." Heart Rhythm 11, no. 5 (May 2014): 864–70. http://dx.doi.org/10.1016/j.hrthm.2014.01.019.

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Fontenla Cerezuela, A., I. Gomez-Blazquez, C. Corros, D. Rodriguez, L. Borrego-Bernabe, A. Marco Del Castillo, J. Ramos-Jimenez, et al. "Left atrial appendage closure in the presence of thrombus: incidence, technique and outcomes." EP Europace 23, Supplement_3 (May 1, 2021). http://dx.doi.org/10.1093/europace/euab116.286.

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Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with left atrial appendage (LAA) thrombus are excluded for LAA occlusion (LAAO) in clinical trials. However, some of them may require this therapy due to repeated thromboembolisms despite accurate anticoagulation. Aim The aim of the study is to describe the prevalence of LAA thrombosis in patients submitted for LAAO in a high-volume center of LAAO procedures, explaining the employed technique and results in this scenario. Methods Single-center retrospective analysis including all consecutive patients referred for LAAO. Results LAA thrombus was detected by TEE in 8/76 patients referred for LAAO (10.5%). Five of them underwent LAAO despite the presence of thrombus due to clinical conditions. All the procedures were successfully performed with Amulet devices (Table). The following preventive measures were putting in place during the implants: avoidance of contrast injection into the LAA during the procedure (non-touch technique), TEE measure for device size election; and TEE device deployment guidance with special care to the the sheath orientation and depth enabling a slow and single implant of the device partially released in the LAA before complete implantation at the entrance of the LAA (Figure. A&B: Large LAA thrombus partially occupying the landing zone. C: Thrombus sealed by LAAO device. D&E: Non-touch technique: echo-guided progressive deployment of the LAAO device without thrombus shifting). No cerebral protection devices were used. TEE performed one month after the procedure ruled out the presence of residual thrombi or leaks in all cases. There were no events after a median follow-up of 17.1 months (range: 32.3-1.1) Conclusion LAAO in patient with LAA thrombus can be effectively and safely performed, in high-volume centers and with an accurate technique, under accurate TEE guidance. Abstract Figure. LAA thrombus and occlusion technique
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García-Villalba, Manuel, Lorenzo Rossini, Alejandro Gonzalo, Davis Vigneault, Pablo Martinez-Legazpi, Eduardo Durán, Oscar Flores, et al. "Demonstration of Patient-Specific Simulations to Assess Left Atrial Appendage Thrombogenesis Risk." Frontiers in Physiology 12 (February 26, 2021). http://dx.doi.org/10.3389/fphys.2021.596596.

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Abstract:
Atrial fibrillation (AF) alters left atrial (LA) hemodynamics, which can lead to thrombosis in the left atrial appendage (LAA), systemic embolism and stroke. A personalized risk-stratification of AF patients for stroke would permit improved balancing of preventive anticoagulation therapies against bleeding risk. We investigated how LA anatomy and function impact LA and LAA hemodynamics, and explored whether patient-specific analysis by computational fluid dynamics (CFD) can predict the risk of LAA thrombosis. We analyzed 4D-CT acquisitions of LA wall motion with an in-house immersed-boundary CFD solver. We considered six patients with diverse atrial function, three with either a LAA thrombus (removed digitally before running the simulations) or a history of transient ischemic attacks (LAAT/TIA-pos), and three without a LAA thrombus or TIA (LAAT/TIA-neg). We found that blood inside the left atrial appendage of LAAT/TIA-pos patients had marked alterations in residence time and kinetic energy when compared with LAAT/TIA-neg patients. In addition, we showed how the LA conduit, reservoir and booster functions distinctly affect LA and LAA hemodynamics. Finally, fixed-wall and moving-wall simulations produced different LA hemodynamics and residence time predictions for each patient. Consequently, fixed-wall simulations risk-stratified our small cohort for LAA thrombosis worse than moving-wall simulations, particularly patients with intermediate LAA residence time. Overall, these results suggest that both wall kinetics and LAA morphology contribute to LAA blood stasis and thrombosis.
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