Review
Engineering, Biomedical
Zheng Xing, Chen Zhao, Siwen Wu, Chunchen Zhang, Haifeng Liu, Yubo Fan
Summary: Therapeutic angiogenesis provides a potential solution for critical limb ischemia by manipulating blood vessel growth in vivo without the need for extra pharmaceutics and surgery. With the rise of interdisciplinary research, regenerative medicine strategies offer new possibilities for treating various clinical diseases.
Review
Biochemistry & Molecular Biology
Lucia Beltran-Camacho, Marta Rojas-Torres, Ma Carmen Duran-Ruiz
Summary: Critical limb ischemia is the most severe form of peripheral arterial disease, commonly caused by atherosclerosis leading to progressive blockage of arterial vessels. For patients not suitable for surgical intervention, angiogenic cell therapy has emerged as a promising alternative, showing potential for enhancing revascularization by promoting vessel formation and blood flow recovery.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Florian Simon, Mansur Duran, Waseem Garabet, Hubert Schelzig, Michael Jacobs, Alexander Gombert
Summary: A decade ago, gene therapy was seen as a potential treatment for chronic limb-threatening ischemia, but its safety and clinical feasibility are still in question. Gene therapy can be achieved through transduction and transfection methods, but there are risks involved, such as increased neo-vascularization in undesired tissue, malignant transformation and inflammation, and arterial thrombosis. Clinical trials of gene therapy in vascular occlusive disease have shown mixed results, leaving the role of gene therapy unclear.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Engineering, Biomedical
Liang Gui, Youlu Chen, Yongpeng Diao, Zuoguan Chen, Jianwei Duan, Xiaoyu Liang, Huiyang Li, Kaijing Liu, Yuqing Miao, Qing Gao, Zhichao Li, Jing Yang, Yongjun Li
Summary: This study introduces a nanoparticle-based gene delivery system using CYP2J2 and EETs for the treatment of CLI, with demonstrated potential in angiogenesis promotion, biocompatibility, high transfection efficiency, and VEGF expression.
MATERIALS TODAY BIO
(2022)
Article
Cell & Tissue Engineering
Pegah Nammian, Seyedeh-Leili Asadi-Yousefabad, Sajad Daneshi, Mohammad Hasan Sheikhha, Seyed Mohammad Bagher Tabei, Vahid Razban
Summary: The study compared the effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) in the treatment of critical limb ischemia (CLI). The results indicated that BM-MSCs had a stronger effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared to AT-MSCs. This suggests that BM-MSC transplantation could be a more effective therapy for diseases with insufficient angiogenesis, such as hindlimb ischemia.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Cell & Tissue Engineering
Zeinab Shirbaghaee, Mohammad Hassani, Saeed Heidari Keshel, Masoud Soleimani
Summary: This article reviews the immunomodulatory features of mesenchymal stem cells (MSCs) and their potential applications as therapeutic agents in the treatment of critical limb ischemia (CLI). Despite advances in clinical research, MSC therapy is still considered experimental and not recommended for regular clinical use. The article provides recommendations to improve the efficacy of cell therapy for CLI patients.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Medicine, General & Internal
Monil Majmundar, Kunal N. Patel, Rajkumar Doshi, Mahesh Anantha-Narayanan, Ashish Kumar, Grant W. Reed, Rishi Puri, Samir R. Kapadia, Ziad A. Jaradat, Deepak L. Bhatt, Ankur Kalra
Summary: This study compared endovascular revascularization (ER) and surgical revascularization (SR) treatment strategies for patients with critical limb ischemia (CLI). The results showed that ER was safer than SR, with no difference in mortality rates, but had an increased risk of major amputation compared to SR. However, the risk of major amputation was similar when both procedures were performed in high-volume centers.
Review
Genetics & Heredity
Vyacheslav Z. Tarantul, Alexander Gavrilenko
Summary: Peripheral artery diseases are a serious public health problem. This review focuses on gene therapy as an alternative and potentially more effective treatment option for no-option patients. The review presents the results of many years of research and application of gene therapy as a treatment for patients with critical limb ischemia, including successful and unsuccessful attempts. The review also highlights trends in changing approaches to therapeutic angiogenesis.
CURRENT GENE THERAPY
(2022)
Article
Medicine, General & Internal
Nunzio Montelione, Vincenzo Catanese, Teresa Gabellini, Francesco Alberto Codispoti, Antonio Nenna, Francesco Spinelli, Francesco Stilo
Summary: This study reported the early and mid-term outcomes of arterialization of the deep venous system in patients with no-option CLTI. The study used duplex ultrasound and angiographic evaluation to improve limb perfusion. The results showed that this method is feasible and effective in limb salvage.
Review
Peripheral Vascular Disease
Stefanos Giannopoulos, Ehrin J. Armstrong
Summary: This review examines guideline-recommended therapies for cardiovascular and limb-related risk reduction in patients with Critical Limb Ischemia (CLI).
Article
Peripheral Vascular Disease
Yuuki Shimizu, Kazuhisa Kondo, Ryo Hayashida, Ken-ichiro Sasaki, Masanori Ohtsuka, Yoshihiro Fukumoto, Shinichiro Takashima, Oto Inoue, Soichiro Usui, Masayuki Takamura, Masashi Sakuma, Teruo Inoue, Tokuichiro Nagata, Yoshihiro J. Akashi, Yoshihiro Yamada, Tamon Kato, Koichiro Kuwahara, Kaoru Tateno, Yoshio Kobayashi, Rei Shibata, Toyoaki Murohara
Summary: This multicenter clinical trial demonstrated that autologous adipose-derived regenerative cell (ADRC) transplantation is safe and effective for therapeutic angiogenesis in patients with critical limb ischemia (CLI). The overall survival rate was 100% at the post-operative period and 6 months follow-up. 94.1% of limbs were free from major amputation for 6 months. The quality of life score, ulcer size, and walking distance also improved in a significant number of patients.
Article
Engineering, Biomedical
Grazia Marsico, Chunseng Jin, Sunny A. Abbah, Eva M. Brauchle, Dilip Thomas, Ana Lucia Rebelo, Doriana Orbanic, Sandrine Chantepie, Paolo Contessotto, Dulce Papy-Garcia, Carlos Rodriguez-Cabello, Michelle Kilcoyne, K. Schenke-Layland, N. G. Karlsson, Karl J. A. McCullagh, Abhay Pandit
Summary: This study demonstrated glycosylation changes associated with ischemia in a murine CLI model, and evaluated the efficacy of an ELR hydrogel for CLI treatment. The ELR hydrogel modulated angiogenic signaling pathways, promoted capillary formation and ECM remodeling, while also inducing arterioles formation, reducing fibrosis, and polarizing anti-inflammatory macrophages. The study suggests a potential role for mannosylation and sialylation in tissue repair, highlighting glycosylation alterations as new therapeutic targets for CLI.
Article
Peripheral Vascular Disease
Wei-Ting Chang, Po-Sen Huang, Li-Wei Su, Chia-Te Liao, Han Siong Toh, Yi-Chen Chen, Chung-Han Ho, Zhih-Cherng Chen, Po -Chao Hsu, Chon-Seng Hong
Summary: This study validates a modified ACD-GENE-CLI score to improve the prediction of major adverse limb events (MALEs) in patients with CLI receiving clopidogrel.
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
(2023)
Article
Peripheral Vascular Disease
Jeremy B. Provance, John A. Spertus, Philip G. Jones, Mark A. Hoffman, Matthew C. Bunte, Todd R. Vogel, Carlos Mena-Hurtado, Kim G. Smolderen
Summary: This study used an EHR database to investigate the 30-day major amputation rates following PVI in patients with CLI. The results showed that amputation rates varied across institutions, and patient-level factors and site characteristics accounted for most of the variation in these rates.
Article
Cardiac & Cardiovascular Systems
Lirong Xu, Yutong Liu, Qianyun Cheng, Yang Shen, Ye Yuan, Xiaolang Jiang, Xu Li, Daqiao Guo, Junhao Jiang, Changpo Lin
Summary: CLI, the most advanced clinical stage of peripheral vascular disease, leads to lower extremity rest pain, ulceration, and gangrene due to insufficient blood and oxygen supply, making effective biomarkers and therapeutic targets crucial. The study confirmed the downregulation of circadian gene Bmal1 in CLI patients, affecting inflammation and angiogenesis. Bmal1 disruption impairs angiogenesis and endothelial cell functions, suggesting its potential as a biomarker and therapeutic target in CLI.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Dror B. Leviner, Tom Friedman, Barak Zafrir, Mattan Arazi, Anastasia Weis, Gil Bolotin, Erez Sharoni
Summary: The morbidity and mortality of isolated tricuspid valve replacement (TVR) may be influenced by certain variables compared to combined TVR and left-sided valve surgery.
ANNALS OF THORACIC SURGERY
(2022)
Article
Peripheral Vascular Disease
Barak Zafrir, Amir Aker, Yosi Asaf, Walid Saliba
Summary: This study investigated the association between blood pressure measurements during exercise stress testing (EST) and the risk of cardiovascular events and the development of hypertension. The results indicated that higher blood pressure levels at rest, submaximal exercise, peak exercise, and recovery were associated with an increased risk of major adverse cardiovascular events (MACE). The association between blood pressure at submaximal exercise and recovery with MACE showed a J-shaped pattern. Among nonhypertensive patients, excessive blood pressure response during peak exercise, as well as submaximal exercise and recovery, were independent predictors of developing hypertension.
JOURNAL OF HYPERTENSION
(2022)
Article
Cardiac & Cardiovascular Systems
Amir Aker, Amnon Eitan, Walid Saliba, Ronen Jaffe, Barak Zafrir
Summary: In elderly patients undergoing coronary angiography, kidney function as measured by eGFR has a graded inverse association with cardiovascular comorbidities and long-term adverse events.
CORONARY ARTERY DISEASE
(2022)
Article
Cardiac & Cardiovascular Systems
Adam Timmis, Panos Vardas, Nick Townsend, Aleksandra Torbica, Hugo Katus, Delphine De Smedt, Chris P. Gale, Aldo P. Maggioni, Steffen E. Petersen, Radu Huculeci, Dzianis Kazakiewicz, Victor de Benito Rubio, Barbara Ignatiuk, Zahra Raisi-Estabragh, Agnieszka Pawlak, Efstratios Karagiannidis, Roderick Treskes, Dan Gaita, John F. Beltrame, Alex McConnachie, Isabel Bardinet, Ian Graham, Marcus Flather, Perry Elliott, Elias A. Mossialos, Franz Weidinger, Stephan Achenbach
Summary: This report updates and expands upon the 2019 report, providing cardiovascular disease statistics for the 57 ESC member countries. The report highlights the determinants of CVD and the disparities among different countries.
EUROPEAN HEART JOURNAL
(2022)
Article
Cardiac & Cardiovascular Systems
Dror B. Leviner, Barak Zafrir, Walid Saliba, Nili Stein, Avinoam Shiran, Erez Sharoni
Summary: There is an interaction between age and outcomes of MV and BV in patients aged 50-70 years, with younger patients (under 65 years) having lower mortality risk with MV. Reoperation is a strong predictor of mortality during the study period.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2022)
Article
Cardiac & Cardiovascular Systems
Amir Aker, Walid Saliba, Barak Zafrir
Summary: This study investigated the interplay of hypertension, obesity, and low cardiorespiratory fitness on the development of atrial fibrillation (AF) in patients without known cardiovascular disease. The study found that obesity, hypertension, and low CRF were independently associated with an increased risk of AF, and the risk was further increased when these three factors coexisted.
HELLENIC JOURNAL OF CARDIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Barak Zafrir, Razi Khoury, Walid Saliba
Summary: This study investigated the association between remnant cholesterol (RC) and the risk for myocardial infarction (MI) in patients with coronary artery disease, and compared its predictive value with non-high-density lipoprotein cholesterol (non-HDL-C). The results showed that elevated RC level was associated with a higher risk for MI, and when RC and non-HDL-C levels were discordant, RC better reflected the risk for MI.
JOURNAL OF CLINICAL LIPIDOLOGY
(2023)
Article
Health Care Sciences & Services
Barak Zafrir, Tal Ovdat, Mahmood Abu Akel, Fadel Bahouth, Katia Orvin, Roy Beigel, Offer Amir, Gabby Elbaz-Greener
Summary: In current clinical practice, ACEI/ARB and beta-blockers are commonly used in HF patients with reduced and mildly-reduced LVEF following ACS, while the utilization of MR antagonists is low and the adoption of SGLT2 inhibitors and ARNI is limited.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Barak Zafrir, Amir Aker, Ibrahim Naoum, Walid Saliba
Summary: Patients with ischemic stroke need intensive lipid-modifying treatment, and combination lipid-lowering therapies are often necessary to achieve treatment goals. However, the use of such therapies and the attainment of LDL-C targets after stroke are suboptimal, especially in the early and long-term periods after hospitalization.
AMERICAN JOURNAL OF CARDIOLOGY
(2023)
Article
Peripheral Vascular Disease
Barak Zafrir, Amir Aker, Walid Saliba
Summary: This study found that extremely elevated Lp(a) levels are associated with a 2.5-fold increased risk of ASCVD compared to normal range levels. It was also observed that treatment for CAD patients with extreme Lp(a) was more intense, but combination therapies were underused and LDL-C goal attainment rates were suboptimal.
INTERNATIONAL JOURNAL OF CARDIOLOGY CARDIOVASCULAR RISK AND PREVENTION
(2023)
Letter
Cardiac & Cardiovascular Systems
Ibrahim Naoum, Barak Zafrir
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2023)
Article
Medicine, General & Internal
Amir Aker, Walid Saliba, Fadel Bahouth, Ibrahim Naoum, Barak Zafrir
Summary: This study found that low cardiorespiratory fitness level is an independent risk predictor for major adverse cardiac events in middle-aged individuals without cardiovascular disease. The association of low fitness with a high burden of cardiometabolic risk factors highlights the importance of lifestyle intervention in this patient population.
JOURNAL OF CLINICAL MEDICINE
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
B. Zafrir, R. Khoury, W. Saliba
Article
Medicine, General & Internal
Nurit Naveh, Yuval Avidan, Barak Zafrir
Summary: The ketogenic diet is popular among patients with obesity and metabolic syndrome, but individuals may respond differently, especially in LDL-C levels. This study presented a case of a normal-weight male who experienced a dramatic elevation in LDL-C levels after starting the ketogenic diet, emphasizing the importance of close monitoring of blood lipid profile.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
B. Zafrir, A. Aker, W. Saliba
EUROPEAN HEART JOURNAL
(2022)
