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1.
Ann Vasc Surg ; 76: 285-288, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1525691

ABSTRACT

The arterial revascularization procedure is still a challenging issue in Covid-19 associated limb ischemia. Herein we aimed to present a case of a 64 year-old woman with acute ischemic signs in upper extremity who was diagnosed as a probable Covid-19 case incidentally after admission. Although late admission and failed recurrent embolectomies lead to an eventful course, intra-arterial thrombolysis seemed to present a benefitable treatment option for our patient.


Subject(s)
COVID-19/complications , Ischemia/etiology , Upper Extremity/blood supply , Acute Disease , Amputation , COVID-19/diagnosis , Embolectomy , Female , Humans , Ischemia/diagnostic imaging , Ischemia/physiopathology , Ischemia/therapy , Middle Aged , Regional Blood Flow , Thrombolytic Therapy , Time-to-Treatment , Treatment Outcome
2.
Ann Vasc Surg ; 76: 289-292, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1525692

ABSTRACT

To describe the case of a young female patient, affected by Systemic Lupus Erythematous, hospitalized for severe SARS-CoV-2 infection pneumonia and presenting a treatment-resistant acute upper limb ischemia. Two days after hospital admission, the patient suffered sudden right upper limb pain associated with mild functional impairment. At physical examination, radial and ulnar pulses were absent, and no flow signal was detected at duplex ultrasound scan. Therefore, an acute limb ischemia diagnoses was posed. Despite several surgical and endovascular revascularization attempts, the patient underwent an above the elbow amputation in 10th postoperative day from first surgical embolectomy, and she died for respiratory failure 25 days after hospitalization. Our case of acute upper limb ischemia seems to confirm that clinical manifestation and fate of thrombotic disorder in COVID-19 patients could be precipitated by concomitant autoimmune diseases.


Subject(s)
COVID-19/complications , Ischemia/etiology , Lupus Erythematosus, Systemic/complications , Upper Extremity/blood supply , Acute Disease , Amputation , COVID-19/diagnosis , COVID-19/therapy , Disease Progression , Embolectomy , Endovascular Procedures , Fatal Outcome , Female , Humans , Ischemia/diagnostic imaging , Ischemia/physiopathology , Ischemia/therapy , Lupus Erythematosus, Systemic/diagnosis , Middle Aged , Treatment Outcome
3.
Trials ; 22(1): 595, 2021 Sep 06.
Article in English | MEDLINE | ID: covidwho-1398873

ABSTRACT

BACKGROUND: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. METHODS: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. DISCUSSION: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Hematopoietic Stem Cell Transplantation , Mesenchymal Stem Cells , Noma , Adipose Tissue , Animals , Clinical Trials, Phase II as Topic , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/therapy , Double-Blind Method , Humans , Ischemia/diagnosis , Ischemia/therapy , Multicenter Studies as Topic , Quality of Life , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
4.
Mol Ther ; 29(10): 3042-3058, 2021 10 06.
Article in English | MEDLINE | ID: covidwho-1331299

ABSTRACT

Reprogramming non-cardiomyocytes (non-CMs) into cardiomyocyte (CM)-like cells is a promising strategy for cardiac regeneration in conditions such as ischemic heart disease. Here, we used a modified mRNA (modRNA) gene delivery platform to deliver a cocktail, termed 7G-modRNA, of four cardiac-reprogramming genes-Gata4 (G), Mef2c (M), Tbx5 (T), and Hand2 (H)-together with three reprogramming-helper genes-dominant-negative (DN)-TGFß, DN-Wnt8a, and acid ceramidase (AC)-to induce CM-like cells. We showed that 7G-modRNA reprogrammed 57% of CM-like cells in vitro. Through a lineage-tracing model, we determined that delivering the 7G-modRNA cocktail at the time of myocardial infarction reprogrammed ∼25% of CM-like cells in the scar area and significantly improved cardiac function, scar size, long-term survival, and capillary density. Mechanistically, we determined that while 7G-modRNA cannot create de novo beating CMs in vitro or in vivo, it can significantly upregulate pro-angiogenic mesenchymal stromal cells markers and transcription factors. We also demonstrated that our 7G-modRNA cocktail leads to neovascularization in ischemic-limb injury, indicating CM-like cells importance in other organs besides the heart. modRNA is currently being used around the globe for vaccination against COVID-19, and this study proves this is a safe, highly efficient gene delivery approach with therapeutic potential to treat ischemic diseases.


Subject(s)
Cellular Reprogramming/genetics , Genetic Therapy/methods , Ischemia/therapy , Muscle, Skeletal/blood supply , Myocardial Infarction/therapy , Neovascularization, Physiologic/genetics , Regeneration/genetics , Transfection/methods , Animals , Animals, Newborn , Cells, Cultured , Disease Models, Animal , Female , Fibroblasts/metabolism , Humans , Male , Mice , Mice, Knockout, ApoE , Myocytes, Cardiac/metabolism , RNA, Messenger/genetics
5.
Ann Vasc Surg ; 76: 285-288, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1305205

ABSTRACT

The arterial revascularization procedure is still a challenging issue in Covid-19 associated limb ischemia. Herein we aimed to present a case of a 64 year-old woman with acute ischemic signs in upper extremity who was diagnosed as a probable Covid-19 case incidentally after admission. Although late admission and failed recurrent embolectomies lead to an eventful course, intra-arterial thrombolysis seemed to present a benefitable treatment option for our patient.


Subject(s)
COVID-19/complications , Ischemia/etiology , Upper Extremity/blood supply , Acute Disease , Amputation , COVID-19/diagnosis , Embolectomy , Female , Humans , Ischemia/diagnostic imaging , Ischemia/physiopathology , Ischemia/therapy , Middle Aged , Regional Blood Flow , Thrombolytic Therapy , Time-to-Treatment , Treatment Outcome
6.
Pediatr Rheumatol Online J ; 19(1): 104, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1292002

ABSTRACT

BACKGROUND: H syndrome (HS) is a rare autoinflammatory disease caused by a mutation in the solute carrier family 29, member 3 (SCL29A3) gene. It has a variable clinical presentation and little phenotype-genotype correlation. The pathognomonic sign of HS is cutaneous hyperpigmentation located mainly in the inner thighs and often accompanied by other systemic manifestations. Improvement after tocilizumab treatment has been reported in a few patients with HS. We report the first patient with HS who presented cardiogenic shock, multiorgan infiltration, and digital ischemia. CASE PRESENTATION: 8-year-old boy born to consanguineous parents of Moroccan origin who was admitted to the intensive care unit during the Coronavirus Disease-2019 (COVID-19) pandemic with tachypnoea, tachycardia, and oliguria. Echocardiography showed dilated cardiomyopathy and severe systolic dysfunction compatible with cardiogenic shock. Additionally, he presented with multiple organ dysfunction syndrome. SARS-CoV-2 polymerase chain reaction (PCR) and antibody detection by chromatographic immunoassay were negative. A previously ordered gene panel for pre-existing sensorineural hearing loss showed a pathological mutation in the SCL29A3 gene compatible with H syndrome. Computed tomography scan revealed extensive alveolar infiltrates in the lungs and multiple poor defined hypodense lesions in liver, spleen, and kidneys; adenopathy; and cardiomegaly with left ventricle subendocardial nodules. Invasive mechanical ventilation, broad antibiotic and antifungal coverage showed no significant response. Therefore, Tocilizumab as compassionate use together with pulsed intravenous methylprednisolone was initiated. Improvement was impressive leading to normalization of inflammation markers, liver and kidney function, and stabilising heart function. Two weeks later, he was discharged and has been clinically well since then on two weekly administration of Tocilizumab. CONCLUSIONS: We report the most severe disease course produced by HS described so far in the literature. Our patient's manifestations included uncommon, new complications such as acute heart failure with severe systolic dysfunction, multi-organ cell infiltrate, and digital ischemia. Most of the clinical symptoms of our patient could have been explained by SARS-CoV-2, demonstrating the importance of a detailed differential diagnosis to ensure optimal treatment. Although the mechanism of autoinflammation of HS remains uncertain, the good response of our patient to Tocilizumab makes a case for the important role of IL-6 in this syndrome and for considering Tocilizumab as a first-line treatment, at least in severely affected patients.


Subject(s)
Cardiomyopathy, Dilated/physiopathology , Hereditary Autoinflammatory Diseases/physiopathology , Ischemia/physiopathology , Multiple Organ Failure/physiopathology , Shock, Cardiogenic/physiopathology , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 , Cardiomyopathy, Dilated/diagnostic imaging , Cardiomyopathy, Dilated/therapy , Child , Glucocorticoids/therapeutic use , Hereditary Autoinflammatory Diseases/diagnosis , Hereditary Autoinflammatory Diseases/genetics , Hereditary Autoinflammatory Diseases/therapy , Humans , Ischemia/therapy , Kidney Diseases/diagnostic imaging , Kidney Diseases/physiopathology , Kidney Diseases/therapy , Liver Diseases/diagnostic imaging , Liver Diseases/physiopathology , Liver Diseases/therapy , Lung Diseases/diagnostic imaging , Lung Diseases/physiopathology , Lung Diseases/therapy , Lymphadenopathy/diagnostic imaging , Lymphadenopathy/physiopathology , Lymphadenopathy/therapy , Male , Methylprednisolone/therapeutic use , Multiple Organ Failure/therapy , Nucleoside Transport Proteins/genetics , Pulse Therapy, Drug , Respiration, Artificial , SARS-CoV-2 , Shock, Cardiogenic/therapy , Splenic Diseases/diagnostic imaging , Splenic Diseases/physiopathology , Splenic Diseases/therapy , Toes/blood supply , Tomography, X-Ray Computed , Treatment Outcome
7.
Semin Vasc Surg ; 34(2): 8-12, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1240793

ABSTRACT

This literature review discusses the current evidence on acute limb ischemia (ALI) in patients with COVID-19. Throughout the pandemic, these patients have been at increased risk of arterial thrombotic events and subsequent mortality as a result of a hypercoagulable state. The exact mechanism of thrombosis is unknown; however arterial thrombosis may be due to invasion of endothelial cells via angiotensin-converting enzyme 2 (ACE2) receptors, endothelial injury from inflammation, or even free-floating aortic thrombus. Multiple studies have been performed evaluating the medical and surgical management of these patients; the decision to proceed with operative intervention is dependent on the patient's clinical status as it relates to COVID-19 and morbidity of that disease. The interventions afforded typically include anticoagulation in patients undergoing palliation; alternatively, thrombectomy (endovascular and open) is utilized in other patients. There is a high risk of rethrombosis, despite anticoagulation, given persistent endothelial injury from the virus. Postoperative mortality can be high in these patients.


Subject(s)
COVID-19/complications , Ischemia/therapy , Ischemia/virology , Lower Extremity/blood supply , Thrombosis/therapy , Thrombosis/virology , Anticoagulants/therapeutic use , COVID-19/diagnosis , COVID-19/therapy , Humans , Ischemia/diagnosis , Thrombectomy , Thrombosis/diagnosis
8.
Vasc Endovascular Surg ; 55(7): 781-786, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1181066

ABSTRACT

The optimal management strategy of acute limb ischemia in non-ventilated patients with COVID-19 is uncertain. We propose that non-ventilated patients who develop COVID-19 related spontaneous arterial thrombosis with associated limb threat may be best suited with percutnaeous revascularization to achieve limb salvage. Herein we describe 5 cases of patients who had severely threatened limbs with complete thrombosis of all 3 tibial arteries who were treated with percutaneous revascularization. All 5 patients were felt to be facing inevitable amputation without revascularization should they survive their COVID hospitalization. We were able to achieve limb salvage in all 5 patients selected for therapy, although 2 ultimately succumbed to respiratory failure.


Subject(s)
Angioplasty, Balloon , Arterial Occlusive Diseases/therapy , COVID-19/complications , Ischemia/therapy , Thrombectomy , Thrombolytic Therapy , Thrombosis/therapy , Aged , Amputation , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/etiology , COVID-19/diagnosis , Fatal Outcome , Humans , Ischemia/diagnostic imaging , Ischemia/etiology , Limb Salvage , Male , Middle Aged , Thrombosis/diagnostic imaging , Thrombosis/etiology , Treatment Outcome
9.
Ann Vasc Surg ; 74: 88-94, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1163381

ABSTRACT

BACKGROUND: COVID-19 is a multisystemic disorder. Hematologic and cardiovascular involvement of COVID-19 causes thromboembolic events across multiple organs which mainly manifest as venous thromboembolism, and rarely, peripheral arterial thromboembolic events. In-situ thrombosis of a healthy, non-atherosclerotic native artery is rare, and COVID-19 has been reported to be a cause of this phenomenon. We aimed to report our institutional experience with COVID-19 patients who developed acute limb ischemia (ALI) during hospitalization or after discharge. METHODS: This was a single-center cross-sectional study. Records of all patients ≥18 years of age admitted to a tertiary center with a confirmed diagnosis of COVID-19 infection between September 1 and December 31, 2020 were retrospectively examined. Data regarding patient demographics, co-morbidities and outcomes were collected. Patients were followed-up during index hospitalization and for 30 days postdischarge. Acute limb ischemia was diagnosed by means of duplex ultrasound and computed tomography angiography in the presence of a clinical suspicion. RESULTS: A total of 681 consecutive patients (38.5% women) were hospitalized with a confirmed diagnosis of COVID-19 during the study period. Median age was 63 years (IQR, 52-74). In-hospital mortality occurred in 94 (13.8%) patients. Ninety (13.2%) patients required intensive care unit admission at some point of their hospital stay. Six (0.9%) patients (one woman) with a median age of 62 years experienced ALI (IQR, 59-64.3). All patients were receiving low molecular weight heparin when they developed ALI. The median of duration between COVID-19 diagnosis and ALI symptom onset was 13 days (IQR, 11.3-14). Three patients underwent emergent surgical thrombectomy combined with systemic anticoagulation, and 3 received systemic anticoagulation alone. Two patients with ALI did not survive to hospital discharge. Among survivors, 1 patient underwent bilateral major amputations, and another underwent a minor amputation within 1 month of hospital discharge. Symptoms of ALI completely resolved in 2 patients without sequelae. CONCLUSIONS: COVID-19 is a multisystemic disorder with involvement of hematologic and cardiovascular systems. Despite widespread use of thromboprophylaxis, hospitalized patients with COVID-19 are at increased risk of ALI, and subsequent limb loss or even death.


Subject(s)
COVID-19/complications , Hospitalization , Ischemia/etiology , Peripheral Arterial Disease/etiology , Acute Disease , Aged , Amputation , Anticoagulants/therapeutic use , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Cross-Sectional Studies , Female , Hospital Mortality , Humans , Ischemia/diagnostic imaging , Ischemia/mortality , Ischemia/therapy , Limb Salvage , Male , Middle Aged , Patient Discharge , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/mortality , Peripheral Arterial Disease/therapy , Retrospective Studies , Risk Assessment , Risk Factors , Thrombectomy , Time Factors , Treatment Outcome
10.
J Thromb Thrombolysis ; 52(3): 974-979, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1163124

ABSTRACT

Coronavirus disease 2019 (COVID-19) has emerged as a pandemic across the world. Hypercoagulability status in COVID-19 is one of the causes of complication from severe COVID-19 with a high risk of arterial thrombosis. Acute Limb Ischemia is a vascular emergency caused by sudden decrease in the arterial perfusion. We report the case of a 53-year-old male patient with COVID-19 Pneumonia, diagnosed with Acute Limb Ischemia. From clinical examination, which included anamnesis, physical examination, and laboratory results as well as chest X-rays, a suspicion of Acute Limb Ischemia was found in a patient with COVID-19 pneumonia. The SARS-CoV-2 real time PCR examination showed positive results. In this patient, the diagnosis of Acute Limb Ischemia with Covid-19 Pneumonia was established through a multidisciplinary approach covering the fields of pulmonology, cardiology, and thoracic and cardiovascular surgery.


Subject(s)
COVID-19/complications , Ischemia/etiology , Lower Extremity/blood supply , Peripheral Arterial Disease/etiology , Thrombosis/etiology , Acute Disease , Anticoagulants/therapeutic use , COVID-19/diagnosis , COVID-19/therapy , Fibrinolytic Agents/therapeutic use , Humans , Ischemia/diagnosis , Ischemia/therapy , Male , Middle Aged , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/therapy , Thrombectomy , Thrombosis/diagnosis , Thrombosis/therapy , Treatment Outcome
11.
Sultan Qaboos Univ Med J ; 21(1): e116-e119, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1156224

ABSTRACT

Objectives: This study aimed to discuss the different challenges faced while managing emergency vascular surgery cases during the COVID-19 pandemic and how these challenges were overcome. Methods: This study details 14 emergency cases that were managed during a period of one month from mid-March to mid-April at Sultan Qaboos University Hospital, Muscat, Oman. The cases included acute limb ischaemia, critical limb ischaemia, type B dissection of the thoracic aorta, thoraco-abdominal aneurysm, critical internal carotid artery stenosis, trauma, infected arteriovenous forearm loop graft and thrombosed arteriovenous fistulas. Results: Only one patient was confirmed to have COVID-19. Five were negative for COVID-19 while the remaining eight were not tested. Various strategies on how the vascular surgical team accommodated changes in hospital protocols and nationwide lockdown are discussed in detail. Conclusions: With the judicious use of personal protective equipment and consumable surgical and endovascular devices, communication with support services and other hospitals and implementation of triage protocols, it was possible to manage vascular surgery emergencies effectively.


Subject(s)
COVID-19/diagnosis , Emergencies , Referral and Consultation , Vascular Diseases/therapy , Vascular Surgical Procedures/methods , Adult , Aged , Aged, 80 and over , Amputation/methods , Aneurysm, Dissecting/therapy , Angioplasty/methods , Aortic Aneurysm/therapy , Arteriovenous Shunt, Surgical , COVID-19/complications , Carotid Stenosis/therapy , Disease Management , Embolectomy/methods , Female , Graft Occlusion, Vascular/complications , Graft Occlusion, Vascular/therapy , Humans , Ischemia/therapy , Lower Extremity , Male , Middle Aged , Oman , SARS-CoV-2 , Tertiary Care Centers , Upper Extremity
14.
Vasc Endovascular Surg ; 55(2): 196-199, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1024339

ABSTRACT

COVID-19 has to date affected over 5 million people worldwide and caused in excess of 300000 deaths. One of the principal finding is that of a thrombotic tendency within the lungs leading to high mortality. There have been increasing number of reports of peripheral arterial thrombosis as well. Most cases of arterial thrombosis is noted in patient in intensive care setting. Here-in we report a case of acute bilateral lower limb arterial thrombosis in a patient recovering at home with mild COVID-19 symptoms, highlighting that patients with milder symptoms may also suffer from prothrombotic state resulting in acute arterial occlusions. Arterial thrombosis should be suspected in these patients despite the absence of predisposing factors.


Subject(s)
Arterial Occlusive Diseases/virology , COVID-19/complications , Ischemia/virology , Lower Extremity/blood supply , Thrombosis/virology , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/therapy , COVID-19/diagnostic imaging , COVID-19/therapy , Humans , Ischemia/diagnostic imaging , Ischemia/therapy , Male , Middle Aged , Thrombosis/diagnostic imaging , Thrombosis/therapy
16.
Ann Vasc Surg ; 70: 314-317, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-739734

ABSTRACT

Thrombotic complications associated with coronavirus disease 2019 (COVID-19) have been described; these have mainly included venous thromboembolic events. Limited literature is available regarding arterial thrombosis. Acute limb ischemia is associated with severe complications that can result in significant morbidity and mortality. Herein, we report 3 cases of COVID-19 infection complicated by arterial thrombosis in the form of acute limb ischemia. Our case series adds to the limited literature regarding arterial thrombosis.


Subject(s)
Arterial Occlusive Diseases/etiology , COVID-19/complications , Ischemia/etiology , Lower Extremity/blood supply , Thrombosis/etiology , Aged , Anticoagulants/therapeutic use , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/therapy , COVID-19/diagnosis , COVID-19/therapy , Fatal Outcome , Female , Humans , Ischemia/diagnostic imaging , Ischemia/therapy , Male , Palliative Care , Thrombolytic Therapy , Thrombosis/diagnostic imaging , Thrombosis/therapy , Treatment Outcome , Vascular Surgical Procedures
17.
Ann Vasc Surg ; 69: 80-84, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-703963

ABSTRACT

Novel 2019 coronavirus (COVID-19) infection usually causes a respiratory disease that may vary in severity from mild symptoms to severe pneumonia with multiple organ failure. Coagulation abnormalities are frequent, and reports suggest that COVID-19 may predispose to venous and arterial thrombotic complications. We report a case of acute lower limb ischemia and resistance to heparin as the onset of COVID-19 disease, preceding the development of respiratory failure. This case highlights that the shift of coagulation profile toward hypercoagulability was associated with the acute ischemic event and influenced the therapy.


Subject(s)
Coronavirus Infections/diagnosis , Ischemia/diagnosis , Ischemia/therapy , Lower Extremity/blood supply , Pneumonia, Viral/diagnosis , Acute Disease , Anticoagulants/administration & dosage , Betacoronavirus , Biomarkers/blood , COVID-19 , Diagnosis, Differential , Diagnostic Imaging , Heparin/administration & dosage , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2 , Thrombectomy , Thrombophilia/complications , Thrombophilia/drug therapy
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