Publications by authors named "Akbarshakh Akhmerov"

22 Publications

  • Page 1 of 1

Supporting the Right Heart - Do It Right and Do It Early.

Ann Thorac Surg 2021 Nov 25. Epub 2021 Nov 25.

Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd, Suite A3105 Los Angeles, CA, 90048. Electronic address:

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http://dx.doi.org/10.1016/j.athoracsur.2021.11.007DOI Listing
November 2021

Engineered Fibroblast Extracellular Vesicles Attenuate Pulmonary Inflammation and Fibrosis in Bleomycin-Induced Lung Injury.

Front Cell Dev Biol 2021 23;9:733158. Epub 2021 Sep 23.

Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, United States.

Pulmonary fibrosis is a progressive disease for which no curative treatment exists. We have previously engineered dermal fibroblasts to produce extracellular vesicles with tissue reparative properties dubbed activated specialized tissue effector extracellular vesicles (ASTEX). Here, we investigate the therapeutic utility of ASTEX and in a mouse model of bleomycin-induced lung injury. RNA sequencing demonstrates that ASTEX are enriched in micro-RNAs (miRs) cargo compared with EVs from untransduced dermal fibroblast EVs (DF-EVs). Treating primary macrophages with ASTEX reduced interleukin (IL)6 expression and increased IL10 expression compared with DF-EV-exposed macrophages. Furthermore, exposure of human lung fibroblasts or vascular endothelial cells to ASTEX reduced expression of smooth muscle actin, a hallmark of myofibroblast differentiation (respectively). , intratracheal administration of ASTEX in naïve healthy mice demonstrated a favorable safety profile with no changes in body weight, lung weight to body weight, fibrotic burden, or histological score 3 weeks postexposure. In an acute phase (short-term) bleomycin model of lung injury, ASTEX reduced lung weight to body weight, IL6 expression, and circulating monocytes. In a long-term setting, ASTEX improved survival and reduced fibrotic content in lung tissue. These results suggest potential immunomodulatory and antifibrotic properties of ASTEX in lung injury.
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http://dx.doi.org/10.3389/fcell.2021.733158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512699PMC
September 2021

Commentary: Expecting the unexpected.

JTCVS Tech 2021 Oct 17;9:85-86. Epub 2021 Aug 17.

Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, Calif.

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http://dx.doi.org/10.1016/j.xjtc.2021.08.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501259PMC
October 2021

Regulatory T cell activation, proliferation, and reprogramming induced by extracellular vesicles.

J Heart Lung Transplant 2021 11 24;40(11):1387-1395. Epub 2021 Jun 24.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Background: Extracellular vesicles (EVs) from heart stromal/progenitor cells modulate innate immunity, with salutary effects in a variety of cardiac disease models. Little is known, however, about the effects of these EVs on adaptive immunity.

Methods: Ex vivo differentiation of naïve CD4 T cells was conducted to assess the effect of EVs on cytokine production and proliferation of Th1, Th2, Th17, and regulatory T (T) cells. These effects were further tested in vivo using the experimental autoimmune myocarditis (EAM) model.

Results: Using differentiated CD4 T cells, we show that EVs secreted by human-derived heart stromal/progenitor cells selectively influence the phenotype, activity, and proliferation of regulatory T (T) cells. Exposure of T cells to EVs results in faster proliferation, augmented production of IL-10, and polarization toward an intermediate FOXP3RORγt phenotype. In experimental autoimmune myocarditis, EVs attenuate cardiac inflammation and functional decline, in association with increased numbers of splenic IL10-T cells.

Conclusions: T cell modulation by EVs represents a novel therapeutic approach to inflammation, harnessing endogenous immunosuppressive mechanisms that may be applied in solid organ transplantation, graft-versus-host disease, and autoimmune disorders.
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http://dx.doi.org/10.1016/j.healun.2021.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570987PMC
November 2021

Mechanical Circulatory Support in Right Ventricular Failure.

Interv Cardiol Clin 2021 04;10(2):185-194

Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Boulevard, Suite A3105, Los Angeles, CA 90048, USA. Electronic address:

Right ventricular dysfunction presents unique challenges in patients with cardiopulmonary disease. When optimal medical therapy fails, mechanical circulatory support is considered. Devices can by classified according to whether they are deployed percutaneously or surgically, whether the pump is axial or centrifugal, whether the right ventricle is bypassed directly or indirectly, and whether the support is short term or long term. Each device has advantages and disadvantages. Acute mechanical circulatory support is a suitable temporizing strategy in advanced heart failure. Future research in right ventricular mechanical circulatory support will optimize device management, refine patient selection, and ultimately improve clinical outcomes.
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http://dx.doi.org/10.1016/j.iccl.2020.12.010DOI Listing
April 2021

Casein-enhanced uptake and disease-modifying bioactivity of ingested extracellular vesicles.

J Extracell Vesicles 2021 01 11;10(3):e12045. Epub 2021 Jan 11.

Cedars-Sinai Medical Center Smidt Heart Institute Los Angeles California USA.

Extracellular vesicles (EVs) from cardiac stromal cells, developed as therapeutic candidates, improve dystrophic muscle function when administered parenterally, but oral delivery remains untested. We find that casein, the dominant protein in breast milk, enhances the uptake and bioactivity of ingested heart-derived EVs, altering gene expression in blood cells and enhancing muscle function in mice with muscular dystrophy. Thus, EVs, administered orally, are absorbed and exert disease-modifying bioactivity . Formulating EVs with casein enhances uptake and markedly expands the range of potential therapeutic applications.
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http://dx.doi.org/10.1002/jev2.12045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798403PMC
January 2021

Atrial and Ventricular Response to Treatment of Premature Ventricular Complexes.

Acta Cardiol Sin 2020 Sep;36(5):475-482

Graduate Institute of Clinical Medical Science, China Medical University.

Background: Premature ventricular complexes (PVC) may cause ventricular dyssynchrony and lead to left atrium and ventricle mechanical abnormalities. Although ventricular cardiomyopathy due to PVCs has been well studied, little is known about atrial adaptation to PVCs.

Objectives: To assess atrial and ventricular responses to PVC therapy.

Methods: All patients with PVC burden > 5000 beats/day on Holter monitoring were enrolled. Baseline demographics, comorbidities, social habits, Holter parameters, and echocardiography profiles were recorded. Follow-up Holter electrocardiography (ECG) and echocardiography data were compared between PVC-treated and non-treated patients.

Results: Two hundred and eighty-six patients were enrolled, of whom 139 received PVC treatment. Among the treated patients, 125 who underwent follow up Holter ECG or echocardiography were included in the final analysis. The mean follow-up times of Holter ECG and echocardiography were 9.40 ± 6.70 and 9.40 ± 5.52 months, respectively. Ventricular arrhythmic burden was significantly reduced in the treatment group (16.46% vs. 13.41%, p = 0.041) but was significantly increased in the observation group (7.58% vs. 14.95%, p = 0.032). A significant increase in left atrial (LA) diameter (36.94 mm vs. 39.46 mm, p = 0.025) and reduction in left ventricular ejection fraction (LVEF) (57.26% vs. 53.8%, p = 0.040) were noted in the observation group. There were no significant differences in supraventricular arrhythmic burden in the observation group and LA diameter and LVEF in the treatment group.

Conclusions: PVC therapy effectively reduced ventricular arrhythmic burden in the treatment group on follow-up. Our data suggest that PVC treatment may prevent LA dilation and LVEF decline.
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http://dx.doi.org/10.6515/ACS.202009_36(5).20200307ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490612PMC
September 2020

Commentary: Engineering antibody therapies may be the future of therapeutics.

J Thorac Cardiovasc Surg 2021 04 27;161(4):1362-1363. Epub 2020 Jun 27.

Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, Calif. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.06.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319912PMC
April 2021

Successful Outcomes following Repair of a Type A Aortic Dissection during Pregnancy.

Aorta (Stamford) 2020 Feb 29;8(1):14-17. Epub 2020 Jun 29.

Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Type A aortic dissections during pregnancy are rare but lethal events, with reported mortalities as high as 60%. Unique changes in hemodynamics, hormone-related alterations in aortic tissue, and preexisting risk factors place patients at an elevated risk for dissection. We report a successful repair of a Type A aortic dissection at 32 weeks of gestation, with excellent outcomes in both mother and child. This report highlights the importance of gestational age and multidisciplinary effort.
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http://dx.doi.org/10.1055/s-0040-1701605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324251PMC
February 2020

Thoracic Endovascular Aortic Repair in Octogenarians and Nonagenarians.

Ann Vasc Surg 2020 Oct 18;68:299-304. Epub 2020 May 18.

Department of Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Division of Vascular Surgery, Cedars-Sinai Medical Center, Los Angeles, CA. Electronic address:

Background: The oldest segments of the population are expanding rapidly, and the number of thoracic endovascular aortic repairs (TEVARs) performed in the elderly parallels this trend. We describe our institutional TEVAR experience in octogenarians and nonagenarians.

Methods: All patients 80 years and older undergoing TEVAR at a single institution were reviewed using a prospectively maintained database. Baselines demographics, operative details, and outcomes were retrospectively analyzed.

Results: Twenty-five octogenarians and nonagenarians (age, 84.8 ± 3.7 years; 64% male) underwent TEVAR between January 2014 and January 2019. The most common preoperative comorbidities were hypertension (n = 24; 96%) and tobacco use (n = 18; 72%), and the mean modified frailty index was 0.32 ± 0.17. Degenerative aneurysms constituted the majority of aortic pathologies (60%), and most patients were symptomatic (64%), with a mean maximal aortic diameter of 62.7 ± 15.6 mm. Endoleaks were noted in 3 (12%) patients. Intensive care unit length of stay was 2.0 (1.5, 3.0) days, and the total length of stay was 5.0 (3.0, 7.0) days. In-hospital mortality was 12% (n = 3), while the overall 30-day mortality was 16% (n = 4). The median follow-up was 469.0 (76.0, 586.0) days. On univariate analysis, the presence of a postoperative complication was associated with a significantly increased risk of 30-day mortality (P < 0.01).

Conclusions: Despite the inherently elevated operative risk among the elderly, this study demonstrates reasonable success rates for TEVAR in octogenarian and nonagenarian patients. In properly selected patients, advanced age alone should not be a prohibitive factor for TEVAR.
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http://dx.doi.org/10.1016/j.avsg.2020.04.066DOI Listing
October 2020

Allogeneic cardiosphere-derived cells (CAP-1002) in critically ill COVID-19 patients: compassionate-use case series.

Basic Res Cardiol 2020 05 12;115(4):36. Epub 2020 May 12.

Cedars-Sinai Medical Center, Smidt Heart Institute, 127 S. San Vicente Boulevard, Advanced Health Sciences Pavilion, Third Floor, Suite A3100, Los Angeles, CA, 90048, USA.

There are no definitive therapies for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Therefore, new therapeutic strategies are needed to improve clinical outcomes, particularly in patients with severe disease. This case series explores the safety and effectiveness of intravenous allogeneic cardiosphere-derived cells (CDCs), formulated as CAP-1002, in critically ill patients with confirmed coronavirus disease 2019 (COVID-19). Adverse reactions to CAP-1002, clinical status on the World Health Organization (WHO) ordinal scale, and changes in pro-inflammatory biomarkers and leukocyte counts were analyzed. All patients (n = 6; age range 19-75 years, 1 female) required ventilatory support (invasive mechanical ventilation, n = 5) with PaO/FiO ranging from 69 to 198. No adverse events related to CAP-1002 administration were observed. Four patients (67%) were weaned from respiratory support and discharged from the hospital. One patient remains mechanically ventilated as of April 28th, 2020; all survive. A contemporaneous control group of critically ill COVID-19 patients (n = 34) at our institution showed 18% overall mortality at a similar stage of hospitalization. Ferritin was elevated in all patients at baseline (range of all patients 605.43-2991.52 ng/ml) and decreased in 5/6 patients (range of all patients 252.89-1029.90 ng/ml). Absolute lymphocyte counts were low in 5/6 patients at baseline (range 0.26-0.82 × 10/µl) but had increased in three of these five patients at last follow-up (range 0.23-1.02 × 10/µl). In this series of six critically ill COVID-19 patients, intravenous infusion of CAP-1002 was well tolerated and associated with resolution of critical illness in 4 patients. This series demonstrates the apparent safety of CAP-1002 in COVID-19. While this initial experience is promising, efficacy will need to be further assessed in a randomized controlled trial.
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http://dx.doi.org/10.1007/s00395-020-0795-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214858PMC
May 2020

COVID-19 and the Heart.

Circ Res 2020 05 7;126(10):1443-1455. Epub 2020 Apr 7.

From the Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA.

Infection with the severe acute respiratory syndrome novel coronavirus produces a clinical syndrome known as 2019 novel coronavirus disease (COVID-19). When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm, and elevations of cardiac injury biomarkers. Here, we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.317055DOI Listing
May 2020

Access to extracorporeal life support as a quality metric: Lessons from trauma.

J Card Surg 2020 Apr 24;35(4):826-830. Epub 2020 Feb 24.

Division of Acute Care Surgery and Surgical Critical Care, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.

Background: Access to centers with extracorporeal membrane oxygenation (ECMO) capabilities varies by region and may affect overall outcomes. We assessed the outcomes of trauma patients requiring ECMO support and compared the overall survival of all patients with trauma at facilities with and without ECMO capabilities.

Methods: A retrospective review of the National Trauma Data Bank was performed to identify all trauma patients receiving care at ECMO and non-ECMO centers. Baseline patient characteristics and outcomes were analyzed. Adjusted odds ratio (OR) was used to compare survival at ECMO and non-ECMO facilities.

Results: Between 2007 and 2015, a total of 5 781 123 patients with trauma were identified with 1 983 986 (34%) admitted to an ECMO facility and 3 797 137 (66%) admitted to a non-ECMO facility. A total of 522 (0.03%) patients required ECMO. Both the number of patients with trauma requiring ECMO support and the number of trauma facilities utilizing ECMO increased over the 9-year-study period (4.9 to 13.8 patients per 100 000 admissions, and 18 to 77 centers, respectively). The mortality for ECMO patients was 40.5%. Patients with trauma admitted to ECMO facilities had more severe injuries (injury severity score: 9.0 vs 8.0; P < .001). The overall mortality was 3.3%. The adjusted OR for mortality associated with admission to an ECMO facility vs a non-ECMO facility was 0.96 (95% confidence interval: 0.95-0.97; adjusted P < .001).

Conclusions: The use of ECMO for patients with trauma is expanding. Our study demonstrates a survival benefit associated with admission to a facility with ECMO capabilities. Thus, access to ECMO is a potential quality metric for trauma centers.
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http://dx.doi.org/10.1111/jocs.14474DOI Listing
April 2020

Successful robotic resection of a primary cardiac synovial sarcoma.

JTCVS Tech 2020 Jun 24;2:104-106. Epub 2020 Feb 24.

Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, Calif.

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http://dx.doi.org/10.1016/j.xjtc.2020.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298838PMC
June 2020

Use of a Dual-Filter Cerebral Embolic Protection Device in Thoracic Endovascular Aortic Repair.

Ann Vasc Surg 2020 May 22;65:54.e1-54.e4. Epub 2020 Jan 22.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Division of Vascular Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA.

Background: The risk of periprocedural stroke after thoracic endovascular aortic repair (TEVAR) ranges from 3% to 8%. Although cerebral embolic protection devices (CEPD) are widely utilized in transcatheter aortic valve replacement, there are currently no Food and Drug Administration approved CEPDs for use in TEVAR. We report our initial experience with the off-label use of a dual-filter CEPD in patients undergoing TEVAR.

Methods: Two patients at high risk for embolic stroke underwent TEVAR for descending thoracic aortic aneurysms (DTAAs) at a single institution. A dual-filter CEPD (Sentinel; Boston Scientific, Marlborough, MA) was used in an off-label fashion in both cases. Patient 1 was a 62-year-old woman with a 6.2-cm DTAA, extending from the left subclavian artery (LSCA) to the diaphragm (Zones 3-5) and associated with extensive atherosclerotic disease of the aortic arch. Patient 2 was a 78-year-old woman with a 6.3-cm DTAA, extending from the LSCA (Zone 2) to the sixth intercostal space (Zone 4) with associated mural thrombus. Given the proximity of the aneurysm to the LSCA, a left carotid-subclavian bypass was performed for planned LSCA coverage.

Results: Through a percutaneous right radial artery approach using a 6F sheath, the Sentinel dual-filter CEPD was delivered over a 0.014″ guidewire into the thoracic aorta. Under fluoroscopic guidance, the 2 filters were sequentially deployed in the innominate and left common carotid arteries, respectively. Appropriately sized devices were successfully delivered and deployed in the proximal and distal landing zones, respectively. Two devices were used for each patient. Completion angiograms showed successful exclusion of the DTAAs in both cases, without evidence of endoleak. The CEPD filters were retrieved in standard fashion without difficulty. Pathology demonstrated successful capture of embolic debris and fibrin clot in both patients. Neither patient exhibited neurological deficits or device-related complications. Both patients remained neurologically intact at 1- and 2-month follow-up, respectively. Surveillance angiograms revealed successful exclusion of the aneurysm without any evidence of endoleak.

Conclusions: We report the novel off-label use of a dual-filter CEPD in 2 patients undergoing TEVAR. Pathological confirmation of embolic debris in the filters makes this a potential tool for stroke prevention during TEVAR in high-risk patients.
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http://dx.doi.org/10.1016/j.avsg.2020.01.077DOI Listing
May 2020

A New Paradigm in Mechanical Circulatory Support: 100-Patient Experience.

Ann Thorac Surg 2020 05 26;109(5):1370-1377. Epub 2019 Sep 26.

Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Background: Acutely decompensated heart failure presents a complicated challenge. Established temporary support measures have significant adverse effects. A minimally invasive temporary left ventricular assist device (LVAD), the Impella 5.0 (Abiomed, Danvers, MA), has been developed to support these patients.

Methods: Patients with acutely decompensated heart failure in whom medical management had failed and who required additional support using an Impella 5.0 device were evaluated from January 2014 to September 2018 at a single center in a retrospective manner using a prospectively maintained database. Patients were treated with the device as a bridge to recovery (BTR; n = 30), bridge to durable device (BTDD; n = 23), or bridge to transplantation (BTT; n = 47). All devices were placed using an axillary artery approach. Demographic features and outcomes were evaluated for each group and compared.

Results: A total of 100 patients underwent insertion of an axillary Impella 5.0 LVAD. Patients had an average age of 56.7 ± 13.2 years, were predominantly male (84%), and had a severely depressed left ventricular ejection fraction (average 16%), and most had an Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 (57%) or 2 (33%) score. When divided into groups, there was no difference in age or INTERMACS score, but a statistical difference was noted in baseline left ventricular ejection fraction (20%, 14%, 15%) and creatinine level (1.0, 2.0, 1.6), in the BTR, BTDD, or BTT group, respectively (all P < .05). Survival was 64% overall, and it was 50%, 48%, and 81% for BTR, BTDD, and BTT, respectively (P = .007). Survival improved during this experience and was 90% overall in the most recent 30 patients.

Conclusions: Use of this minimally invasive LVAD system is an attractive strategy to support patients with acute decompensated heart failure to recovery, durable LVAD, or heart transplantation.
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http://dx.doi.org/10.1016/j.athoracsur.2019.08.041DOI Listing
May 2020

Augmenting canonical Wnt signalling in therapeutically inert cells converts them into therapeutically potent exosome factories.

Nat Biomed Eng 2019 09 26;3(9):695-705. Epub 2019 Aug 26.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Cardiosphere-derived cells are therapeutic candidates with disease-modifying bioactivity, but their variable potency has complicated their clinical translation. Transcriptomic analyses of cardiosphere-derived cells from human donors have revealed that their therapeutic potency correlates with Wnt/β-catenin signalling and with β-catenin protein levels. Here, we show that skin fibroblasts engineered to overexpress β-catenin and the transcription factor Gata4 become immortal and therapeutically potent. Transplantation of the engineered fibroblasts into a mouse model of acute myocardial infarction led to improved cardiac function and mouse survival, and in the mdx mouse model of Duchenne muscular dystrophy, exosomes secreted by the engineered fibroblasts improved exercise capacity and reduced skeletal-muscle fibrosis. We also demonstrate that exosomes from high-potency cardiosphere-derived cells exhibit enhanced levels of miR-92a (a known potentiator of the Wnt/β-catenin pathway), and that they activate cardioprotective bone-morphogenetic-protein signalling in cardiomyocytes. Our findings show that the modulation of canonical Wnt signalling can turn therapeutically inert mammalian cells into immortal exosome factories for cell-free therapies.
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http://dx.doi.org/10.1038/s41551-019-0448-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736698PMC
September 2019

Effect of Percutaneous Suction Thromboembolectomy on Improved Right Ventricular Function.

Tex Heart Inst J 2019 Apr 1;46(2):115-119. Epub 2019 Apr 1.

Venous thromboembolism is a leading cause of cardiovascular death. Historically, surgical intervention has been associated with high morbidity rates. Pharmacologic therapy alone can be inadequate for patients with substantial hemodynamic compromise, so minimally invasive procedures are being developed to reduce clot burden. We describe our initial experience with using the AngioVac system to remove thromboemboli percutaneously. We reviewed all suction thromboembolectomy procedures performed at our institution from March 2013 through August 2015. The main indications for the procedure were failed catheter-directed therapy, contraindication to thrombolysis, bleeding-related complications, and clot-in-transit phenomena. We collected details on patient characteristics, procedural indications, thrombus location, hemodynamic values, cardiac function, pharmacologic support, and survival to discharge from the hospital. The Wilcoxon signed-rank test was used for statistical analysis. Thirteen patients (mean age, 56 ± 15 yr; 10 men) underwent suction thromboembolectomy; 10 (77%) survived to hospital discharge. The median follow-up time was 74 days (interquartile range [IQR], 23-221 d). Preprocedurally, 8 patients (62%) had severe right ventricular dysfunction; afterwards, 11 (85%) had normal function or mild-to-moderate dysfunction, and only 2 (17%) had severe dysfunction (=0.031). Percutaneous suction thromboembolectomy, a promising therapeutic option for patients, appears to be safe, and we found it to be associated with improved right ventricular function.
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http://dx.doi.org/10.14503/THIJ-17-6551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555294PMC
April 2019

Blunt Thoracic Aortic Injury: Current Therapies, Outcomes, and Challenges.

Ann Vasc Dis 2019 Mar;12(1):1-5

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Blunt thoracic aortic injuries are rare occurrences but carry an increased risk of mortality. Over the last two decades, however, major advances in diagnostic imaging, staging, and treatment have significantly improved outcomes. Modern imaging paved the way for a new staging system based on the anatomical layers of the aortic wall. This staging system, in turn, allowed for refinement of treatment, which now includes nonoperative management with anti-impulse therapy, endovascular intervention, and, if needed, open surgical repair. As is the case with any other rapidly evolving therapy, however, new challenges and controversies arise. The resolution of these challenges will rely on a broad, international, and multidisciplinary effort. (This is a review article based on the invited lecture of the 46th Annual Meeting of Japanese Society for Vascular Surgery.).
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http://dx.doi.org/10.3400/avd.ra.18-00139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434345PMC
March 2019

The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas.

Neurosurgery 2018 06;82(6):808-814

Depart-ment of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs.

Objective: To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs.

Methods: We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan-Meier method.

Results: Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively).

Conclusion: Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.
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http://dx.doi.org/10.1093/neuros/nyx265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571505PMC
June 2018

Ablation of astrocytic laminin impairs vascular smooth muscle cell function and leads to hemorrhagic stroke.

J Cell Biol 2013 Jul 15;202(2):381-95. Epub 2013 Jul 15.

Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065, USA.

Astrocytes express laminin and assemble basement membranes (BMs) at their endfeet, which ensheath the cerebrovasculature. The function of astrocytic laminin in cerebrovascular integrity is unknown. We show that ablation of astrocytic laminin by tissue-specific Cre-mediated recombination disrupted endfeet BMs and led to hemorrhage in deep brain regions of adult mice, resembling human hypertensive hemorrhage. The lack of astrocytic laminin led to impaired function of vascular smooth muscle cells (VSMCs), where astrocytes have a closer association with VSMCs in small arterioles, and was associated with hemorrhagic vessels, which exhibited VSMC fragmentation and vascular wall disassembly. Acute disruption of astrocytic laminin in the striatum of adult mice also impaired VSMC function, indicating that laminin is necessary for VSMC maintenance. In vitro, both astrocytes and astrocytic laminin promoted brain VSMC differentiation. These results show that astrocytes regulate VSMCs and vascular integrity in small vessels of deep brain regions. Therefore, astrocytes may be a possible target for hemorrhagic stroke prevention and therapy.
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http://dx.doi.org/10.1083/jcb.201212032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718965PMC
July 2013
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