LEA 13. Safety and Effectiveness of a New Valvulotome: Insights From the LIMBSAVE Registry (treatment of critical Limb IscheMia with infragenicular Bypass adopting in situ SAphenous VEin technique)

Objectives Guidelines recommend open bypass surgery for long occlusions of infrainguinal arteries. In situ saphenous vein bypass is a standardized technique. The aim of this study was to report preliminary six-month outcomes of a national, multicenter, observational, prospective registry based on the examination of treatment of critical Limb IscheMia with infragenicular Bypass adopting the in situ SAphenous VEin technique (LIMBSAVE). Methods From January 2018 until October 2019, 428 patients from 41 centers were enrolled in the LIMBSAVE registry. Data were prospectively collected in a dedicated database, including demographics, preoperative risk factors, clinical and diagnostic preoperative assessments, intraoperative measures (including safety and effectiveness of the valvulotome during the surgical procedures), and 30-day follow-up data. Furthermore, estimated six-month outcomes according to Kaplan–Meier curves in terms of primary patency, primary assisted patency, secondary patency, and limb salvage were evaluated. Results Patients were predominantly male ( n = 332, 77.6%) with a mean age of 73.3 years (range 39–95). Technical success, defined as bypass pulse after use of the valvulotome, was obtained in all cases. The proximal anastomosis could be reached by the valvulotome in all cases. The mean number of valvulotome uses was 2.5 (range 1–5). No vein perforation was reported. In nine cases (2.1%), a vein lesion with intramural hemorrhage occurred. The mean length of hospital stay was 11.1 days (range 1–60). At 30-day follow-up, the overall bypass patency rate was 97.4%, and the rate of open or endo reinterventions for failing bypass was 5.4%. At six-month follow-up, the estimated primary patency, primary assisted patency, secondary patency, and limb salvage were 78.1%, 86.2%, 92.1%, and 94.7%, respectively. Conclusions Preliminary intraprocedural outcomes of the LIMBSAVE registry show that the in situ technique with the valvulotome is safe and effective in disrupting valves and obtaining pulsatility in the saphenous vein. The complication rate related to the use of the valvulotome is low. The six-month preliminary outcomes in terms of overall patency and limb salvage are promising. Further examinations and continuous follow-up are needed to evaluate long-term outcomes.

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Treatment of critical limb ischemia with infragenicular bypass adopting the in-situ saphenous vein technique: protocol for a national, multicenter, observational, prospective registry (LIMBSAVE)

Italian Journal of Vascular and Endovascular Surgery ◽

10.23736/s1824-4777.18.01378-5 ◽

2019 ◽

Vol 26 (1) ◽

Cited By ~ 3

Author(s):

Nicola Troisi ◽

Giovanni De Blasis ◽

Mauro Salvini ◽

Stefano Michelagnoli ◽

Keyword(s):

Critical Limb Ischemia ◽

Saphenous Vein ◽

Limb Ischemia

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Deciphering the in vivo Dynamic Proteomics of Mesenchymal Stem Cells in Critical Limb Ischemia

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.682476 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yipeng Du ◽

Xiaoting Li ◽

Wenying Yan ◽

Zhaohua Zeng ◽

Dunzheng Han ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Protein Synthesis ◽

Critical Limb Ischemia ◽

Click Reaction ◽

Limb Ischemia ◽

Trna Synthetase ◽

Doppler Imaging

ObjectiveRegenerative therapy using mesenchymal stem cells (MSC) is a promising therapeutic method for critical limb ischemia (CLI). To understand how the cells are involved in the regenerative process of limb ischemia locally, we proposed a metabolic protein labeling method to label cell proteomes in situ and then decipher the proteome dynamics of MSCs in ischemic hind limb.Methods and ResultsIn this study, we overexpressed mutant methionyl-tRNA synthetase (MetRS), which could utilize azidonorleucine (ANL) instead of methionine (Met) during protein synthesis in MSCs. Fluorescent non-canonical amino-acid tagging (FUNCAT) was performed to detect the utilization of ANL in mutant MSCs. Mice with hindlimb ischemia (HLI) or Sham surgery were treated with MetRSmut MSCs or PBS, followed by i.p. administration of ANL at days 0, 2 6, and 13 after surgery. FUNCAT was also performed in hindlimb tissue sections to demonstrate the incorporation of ANL in transplanted cells in situ. At days 1, 3, 7, and 14 after the surgery, laser doppler imaging were performed to detect the blood reperfusion of ischemic limbs. Ischemic tissues were also collected at these four time points for histological analysis including HE staining and vessel staining, and processed for click reaction based protein enrichment followed by mass spectrometry and bioinformatics analysis. The MetRSmut MSCs showed strong green signal in cell culture and in HLI muscles as well, indicating efficient incorporation of ANL in nascent protein synthesis. By 14 days post-treatment, MSCs significantly increased blood reperfusion and vessel density, while reducing inflammation in HLI model compared to PBS. Proteins enriched by click reaction were distinctive in the HLI group vs. the Sham group. 34, 31, 49, and 26 proteins were significantly up-regulated whereas 28, 32, 62, and 27 proteins were significantly down-regulated in HLI vs. Sham at days 1, 3, 7, and 14, respectively. The differentially expressed proteins were more pronounced in the pathways of apoptosis and energy metabolism.ConclusionIn conclusion, mutant MetRS allows efficient and specific identification of dynamic cell proteomics in situ, which reflect the functions and adaptive changes of MSCs that may be leveraged to understand and improve stem cell therapy in critical limb ischemia.

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