Knowledge gaps in surgical management for aortic dissection.

Aortic dissection (AD) is recognized as a potentially fatal condition and its standard treatment has been surgical intervention for acute type A AD (TAAD) and complicated acute type B AD (TBAD), and medical management for uncomplicated acute type B AD. Due to rapidly evolving device technologies and minimally invasive surgical techniques that have lowered perioperative risk, there are paradigm shifts for the indications and treatment options for both TAAD and TBAD. In this article, we will discuss the current indications and treatment options for TAAD and TBAD by chronicity of the disease, which comprises four categories: acute TAAD, chronic (repaired) TAAD, acute TBAD, and chronic TBAD. We will also discuss the knowledge gaps in the current surgical management strategies and literature evidence. Open surgical intervention remains the reference standard for acute TAAD and chronic TAAD with complications until an endoprosthesis that will suit the complex anatomy of aortic root, ascending aorta, and aortic arch is developed. Thoracic endovascular aortic repair is now the first line for complicated acute and chronic TBADs. However, we need a larger trials to support the safety and durability of the procedures in patients with uncomplicated TBAD. Without additional data, patients are left to choose between existing treatment options, such as open surgical repair and stent-grafting.

Efficacy and safety of intramuscular administration of allogeneic adipose tissue derived and expanded mesenchymal stromal cells in diabetic patients with critical limb ischemia with no possibility of revascularization: study protocol for a randomized controlled double-blind phase II clinical trial (The NOMA Trial).

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.

Corrigendum: Cost-Effective, Safe, and Personalized Cell Therapy for Critical Limb Ischemia in Type 2 Diabetes Mellitus.

[This corrects the article DOI: 10.3389/fimmu.2019.01151.].

Cost-Effective, Safe, and Personalized Cell Therapy for Critical Limb Ischemia in Type 2 Diabetes Mellitus.

Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI.

Prognostic significance of an elevated neutrophil-lymphocyte ratio in the amputation-free survival of patients with chronic critical limb ischemia.

BACKGROUND: The aim of this study was to investigate the utility of admission neutrophil-lymphocyte ratio (NLR) in predicting the amputation-free survival (AFS) of patients with critical limb ischemia (CLI) who underwent an elective infrainguinal therapeutic intervention. METHODS: All patients with CLI undergoing elective infrainguinal vascular surgery (open or endovascular) at a single university teaching hospital between January 2005 and December 2009 were retrospectively identified from a prospectively maintained database. The primary end point was AFS. The cut-off of NLR >5 was used to categorize patients into low- and high-NLR groups. Kaplan-Meier analysis and long-rank test were used to compare survival between both groups. Cox regression analysis was conducted to determine independent factors affecting the AFS. RESULTS: During a median follow-up of 31 months, 561 patients with chronic CLI underwent infrainguinal revascularization. Five-year mortality was lower in the NLR <5 group (33%) than in the NLR >5 group (49%) (P ≤ 0.001), and the AFS was significantly higher in the NLR <5 group (50%) than in the NLR >5 group (26%) (P ≤ 0.001). In a multivariate analysis, preoperative NLR >5 was independently associated with 5-year AFS (hazard ratio 2.325, 95% CI 1.732-3.121). CONCLUSIONS: Elevated NLR predicts a worse AFS in patients undergoing infrainguinal vascular revascularization with chronic CLI, suggesting that the NLR conveys powerful prognostic information that is independent of other conventional clinical risk factors.