Acute limb ischemia (ALI) due to arterial thromboembolic occlusion is a critical emergency in vascular medicine, requiring attention for rapid diagnosis and intervention, to prevent limb loss and major amputation, which is associated with patient disability in the long term. Traditionally, surgical embolectomy has been used for the treatment of ALI. Endovascular treatment of ALI traditionally involved catheter-directed thrombolysis. This option, however, poses some limitations, including an increased risk for access site and systemic bleeding complications, especially in patients with high bleeding risk. Therefore, in the last decades, several devices have been developed and tested for the mechanical endovascular treatment of ALI. Such devices involve either rotational thrombectomy or continuous thrombus aspiration. While rotational thrombectomy is limited in rather large arteries due to the risk of dissection and perforation in arteries <3 mm, continuous thrombus aspiration can be applied in smaller vessels and tortuous anatomies. In our case series we present a minimal-invasive endovascular approach for the treatment of two patients with ALI due to thrombotic occlusion of tortious and small diameter arteries. Minimal-invasive mechanical thrombectomy using the Penumbra Aspiration System emerged as a successful alternative to surgical embolectomy, enabling prompt treatment and with a short hospital stay for both patients. Our article therefore highlights the use of continuous thrombus aspiration in small diameter vessels and tortuous anatomies, which may represent a contraindication for the use of rotational thrombectomy. In addition, this technique may be applied even in patients with higher bleeding risk since additional lysis is not necessary in patients, where complete thrombus removal can be achieved by this device.

OBJECTIVE: Acute aortic occlusion (AAO), though rare, carries a high morbidity and mortality risk. Rapid recognition and revascularization are crucial for limb and life preservation. We present a case of a hybrid approach using open thrombectomy and endovascular arterial stent grafts in lieu of an open bypass for management of AAO.
METHODS: This case describes a 77-year-old man who presented with new-onset lower extremity pain with associated sensory deficits and was found to have acute infrarenal aortic occlusion. Open femoral cutdown for open thrombectomy and distal embolic protection with endovascular balloon occlusion was combined with aortic and bilateral iliac artery stenting.
RESULTS: The patient was discharged home on post-operative day 3 with resolution of his presenting symptoms and remains asymptomatic at 1-month follow-up.
CONCLUSIONS: This technique of aorto-iliac reconstruction using stent grafts has previously been described in the setting of chronic aorto-iliac occlusive disease; however, its use has not been previously documented in the setting of acute aortic occlusion. This case illustrates the safety and feasibility of a hybrid approach to AAO, particularly in patients who are physiologically unfit for open revascularization.

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Aim: This study aims to investigate the effects of large extracellular vesicles (EVs) induced by pluripotent stem cell-derived mesenchymal stem cells on lower limb ischemic disease and explore its potential mechanisms. Materials & methods: The pathology of muscles was accessed by H&E staining and immunofluorescence staining. In vitro, we conducted wound-healing assay, tube formation assay, RT qPCR, ELISA, RNA sequencing and proteomic analysis. Results: iMSCs-lEVs alleviated the injury of ischemic lower limb and promoted the recovery of lower limb function. In vitro, iMSCs-lEVs promoted the proliferation, migration, and angiogenesis of HMEC-1 cells by regulating the ERK/MAPK signing pathway. Conclusion: This study demonstrated that iMSCs-lEVs promoted endothelial cell angiogenesis via the ERK/MAPK signaling pathway, thereby improving function after lower limb ischemic injury.
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Neonatal aortic thrombosis, though rare, is associated with high mortality and is frequently linked to umbilical vessel catheterization, especially in smaller and critically ill infants due to their low levels of natural anticoagulants and increased prothrombotic activity. We report a case of a term neonate with abdominal aortic thrombosis and severe lower limb ischemia, presenting with respiratory distress requiring intubation and subsequent development of thrombosis by day 7. Initial anticoagulation with heparin proved insufficient, necessitating the use of reteplase and intra-arterial thrombolysis, which resulted in clinical improvement despite limited immediate success in Doppler studies. The patient was discharged on low-molecular-weight heparin against medical advice, highlighting the complexities and need for individualized management strategies in neonatal thromboembolism.

BACKGROUND: The heparin-bonded expanded polytetrafluoroethylene (He-ePTFE) conduit is an option for patients requiring infrainguinal revascularization (iIR), but the risk of failure may be unpredictable, especially in cases with poor run-off. Intraoperative transit-time flow (TTF) provides an automated and quantitative analysis of flow and may serve as an adjunct evaluation during surgical revascularization. The aim of this study was to assess TTF in patients undergoing iIR with He-PTFE at 3 referral hospitals and to establish a predictive flow threshold for graft occlusion.
METHODS: A prospective registry initiated in 2020 enrolled patients undergoing iIR using He-PTFE for critical limb ischemia or severe claudication, and TTF measurement was analyzed. Preoperative assessments of anatomical and clinical characteristics were available for all patients. The HT353 Optima Meter (Transonic Systems Inc., Ithaca, NY, USA) was used in all procedures according to a standardized protocol. The institutional ethics committee approved the study. A predictive model using receiver operating characteristic curve analysis was utilized to establish the threshold of flow, and variables were compared. Anatomical and clinical evaluation were reported according to Rutherford grade, Global Limb Anatomic System and Wound, Ischemia, and foot Infection classification. The main outcome considered was the correlation between TTF and graft occlusion. Secondary outcomes included survival, other predictors of graft occlusion, freedom from major adverse cardiovascular events, and freedom from major amputation.
RESULTS: Among 68 patients, 55.8% had Rutherford 5-6, 45.6% had Global Limb Anatomic System 3 and 73.5% had Wound, Ischemia, and foot Infection 3-4. Distal anastomosis was at tibial level in 23.5% and mean diameter of conduit was 6.4 mm. Basal and postoperative TTF were 27.8 ± 15.6 ml/min and 109.0 ± 53.0 ml/min, respectively. After a mean follow-up of 18 ± 13 months, 7 (10.9%) patients presented graft occlusion and 5 (7.8%) required major amputation. TTF threshold = 80 ml/min revealed a sensitivity and specificity of 81.8% (95% confidence interval 48.2-97.7) and 80.7% (95% confidence interval 68.1-90.0) respectively, and it was selected as cut-off for graft occlusion. Freedom from graft occlusion in patients with TTF >80 ml/min vs. TTF ≤80 ml/min at 6, 12, and 24 months was 95.7% (standard error (SE) = 0.030) vs. 65.5% (SE = 0.115), 95.7% (SE = 0.030) vs. 58.9% (SE = 0.120) and 90.9% (SE = 0.054) vs. 51.6% (SE = 0.126), P = 0.0003. No statistical difference in primary patency, secondary patency and limb salvage was observed. At multivariate analysis, distal anastomosis at tibial vessel (odds ratio 8.50) and TTF ≤80 ml/min (odds ratio 9.39) were independent predictors of graft occlusion.
CONCLUSIONS: These results suggest that TTF may serve as a valuable tool in the management of iIR. A TTF measurement of ≤80 ml/min should be regarded as a predictor of graft occlusion, prompting consideration of additional intraoperative maneuvers to enhance arterial flow. Caution should be exercised in patients requiring direct tibial artery revascularization, as it represents a predictor of failure independent of TTF levels. Larger cohorts of patients and longer follow-up periods are necessary to confirm these findings.

BACKGROUND: Large cannulae can increase cannula-related complications during venoarterial extracorporeal membrane oxygenation (VA ECMO). Conversely, the ability for small cannulae to provide adequate support is poorly understood. Therefore, we aimed to evaluate a range of cannula sizes and VA ECMO flow rates in a simulated patient under various disease states.
METHODS: Arterial cannulae sizes between 13 and 21 Fr and drainage cannula sizes between 21 and 25 Fr were tested in a VA ECMO circuit connected to a mock circulation loop simulating a patient with severe left ventricular failure. Systemic and pulmonary hypertension, physiologically normal, and hypotension were simulated by varying systemic and pulmonary vascular resistances (SVR and PVR, respectively). All cannula combinations were evaluated against all combinations of SVR, PVR, and VA ECMO flow rates.
RESULTS: A 15 Fr arterial cannula combined with a 21 Fr drainage cannula could provide >4 L/min of total flow and a mean arterial pressure of 81.1 mmHg. Changes in SVR produced marked changes to all measured parameters, while changes to PVR had minimal effect. Larger drainage cannulae only increased maximum circuit flow rates when combined with larger arterial cannulae.
CONCLUSIONS: Smaller cannulae and lower flow rates could sufficiently support the simulated patient under various disease states. We found arterial cannula size and SVR to be key factors in determining the flow-delivering capabilities for any given VA ECMO circuit. Overall, our results challenge the notion that larger cannulae and high flows must be used to achieve adequate ECMO support.

Although the formation of NETs contributes to cancer cell invasion and distant metastasis, its role in the pathological progression of limb ischemia remains unknown. This study investigated the functional significance of NETs in cell-cell crosstalk during limb ischemia. The changes of cell subsets in lower limb ischemia samples were detected by single-cell RNA sequencing. The expression of neutrophil extracellular traps (NETs) related markers in lower limb ischemia samples was detected by immunohistochemistry and Western blotting. The signaling pathway of NETs activation in fibroblasts was verified by immunofluorescence, PCR and Western blotting. Through single-cell RNA sequencing (scRNA-seq), we identified 9 distinct cell clusters, with significantly upregulated activation levels in fibroblasts and neutrophils and phenotypic transformation of smooth muscle cells (SMCs) into a proliferative state in ischemic tissue. At the same time, the interaction between fibroblasts and smooth muscle cells was significantly enhanced in ischemic tissue. NETs levels rise and fibroblast activation is induced in ischemic conditions. Mechanistically, activated fibroblasts promote smooth muscle cell proliferation through the Wnt5a pathway. In ischemic mice, inhibition of Wnt5a mitigated vascular remodeling and subsequent ischemia. These findings highlighting the role of cell-cell crosstalk in ischemia and vascular remodeling. We found that the NETs-initiated fibroblast-SMC interaction is a critical regulator of limb ischemia via Wnt5a pathway, a potential therapeutic target for the treatment.

This article presents the case of a 57-year-old woman with a history of rheumatoid arthritis who developed severe coronavirus disease 2019 (COVID-19) pneumonia that progressed to acute respiratory distress syndrome (ARDS) and multi-system organ failure. Despite initial slow progression and multiple hospital readmissions, her condition rapidly deteriorated, leading to full respiratory failure requiring intubation and ventilation. She was transferred to a specialized center where she underwent extracorporeal membrane oxygenation (ECMO) and hemodialysis for acute renal failure. Unfortunately, she remained dependent on ECMO for an extended period of six months. Although she made a gradual recovery, the prolonged critical care treatment resulted in critical ischemia of multiple extremities, necessitating a below-knee amputation (BKA) of her left lower extremity and transmetatarsal amputations of her right hand. This case reports one of the longest ECMO treatments for COVID-19 and associated comorbidities in the literature. Clinicians could include a longer duration of treatment and potential associated disabilities in the informed consent.

Objective This study aimed to investigate the causes of amputation and the associated biochemical parameters in patients with acute limb ischemia (ALI). Methods Patients who presented to our clinic with ALI between January 2012 and January 2022 were deemed eligible for participation. Patients who developed ALI owing to atherosclerosis or atrial fibrillation were included in the study. In contrast, patients who developed ALI owing to trauma, iatrogenic causes, or popliteal artery aneurysms were excluded. Patients\' demographic data, biochemical parameters, and hemogram values at the time of admission were retrospectively analyzed. Results A total of 374 patients were included in the study. Of them, 57.82% (n = 218) were male and 42.18% (n= 156) were female. Amputation was required in 7.95% (n = 30) of the patients after presenting with ALI and receiving necessary surgical or medical intervention. Multivariate analysis revealed the symptom-to-door time to be the primary factor determining the need for amputation in patients. With each passing hour following the manifestation of symptoms, the risk of amputation increased by 1.3 times [odds ratio (OR): 1.289%, 95% confidence interval (CI): 1.079-1.540 p = 0.05]. The neutrophil-to-lymphocyte ratio (NLR) and other hematological parameters had no effect on amputation in both univariate and multivariate analyses (OR: 1.49%; 95% CI: 0.977-2.287 p = 0.512). Conclusions Based on our findings, the main factor affecting the need for amputation in ALI patients was the symptom-to-door time. Biochemical and hematological parameters had no effect on amputation in ALI.