COVID-19 Related Acute Lower Limb Ischemia Treated Via Percutaneous Thrombectomy and Catheter Direct Thrombolisis

Background: The aim of this report is to describe and discuss a unique case of acute lower limb ischemia presented in a recovered COVID-19 patient treated via percutaneous mechanical thrombectomy and catheter directed thrombolysis. Starting from this singular case a wide literature review regarding COVID-19-related thrombo-embolic complications has been accomplished. Methods: A 47-year-old male was admitted to the emergency unit with acute lower limb ischemia three weeks after testing positive for COVID-19. He had been isolated at home because of minor COVID-19-related symptoms. Angio-CT-imaging showed a segmental occlusion of the common iliac artery coupled with retro-articular popliteal artery and leg vessels thrombosis. The patient was first unsuccessfully submitted to trans-femoral iliac thrombo-embolectomy. Results: Instead of peripheral limb vessel re-thromboembolectomy, a percutaneous mechanical thrombectomy coupled with leg vessel catheter direct thrombolysis was performed. The completion angiography showed the recanalization of the popliteal artery and leg vessels as far as the ankle but with a reduced forefoot vascularization. The fibrinolytic treatment was continued for 8 hours post-operatively. A compartment syndrome complicated the early post-operative course. There was a progressive recovery of ischemic symptoms and at 6-month follow-up, peripheral pulses were palpable with an almost complete normalization of foot and toe perfusion and motility. Conclusion: Acute lower limb ischemia following COVID-19-related arterial thrombo-embolic events represents a severe complication of COVID-19 infection and may result in a high rate of revascularization failure. In these cases, Percutaneous Mechanical thrombectomy coupled with catheter directed thrombolysis might represent a less traumatic and more selective approach.

Acute Lower Limb Ischemia in COVID-19 Patient with Delayed Presentation

Thromboembolism is a common complication of SARS-CoV-2, which generally involves venous thromboembolism, although there have been reported cases of arterial thrombosis affecting cerebral, coronary, and visceral arteries, as well as arteries in the extremities. We discuss a case of a 45-year-old diabetic man with COVID-19 who developed late-onset acute lower limb ischemia.

Genetics of Vascular Inflammation in Lower Limb Ischemia: The TNF-α Hypothesis in Peripheral Arterial Disease

Background: Vascular inflammation plays a crucial role in peripheral arterial disease (PAD), although the role of the mediators involved has not yet been properly defined. The aim of this work is to investigate gene expression and plasma biomarkers in chronic limb-threating ischemia (CLTI). Methods: Using patients from the GHAS trial, both blood and ischemic muscle samples were obtained to analyze plasma markers and mRNA expression, respectively. Statistical analy-sis was performed by using univariate (Spearman, t-Student, X2) and multivariate (multiple lo-gistic regression) tests. Results: 35 patients were available at baseline (29 for mRNA expression). Baseline characteristics (mean): Age:71.4±12.4 (79.4% male); TNF-α:10.7±4.9; hs-CRP:1.6±2.2; Neutrophil-to-lymphocyte ratio (NLR):3.5±2.8. Plasma TNF-α was found elevated (≥8.1) in 68.6% of patients, while high hs-CRP (≥0.5) in 60.5%. Diabetic patients with high level of inflammation showed significantly higher levels of NOX4 expression at baseline (p=0.0346). Plasma TNF-α had a negative correlation with eNOS expression (-0.5, p=0.015) and hs-CRP with VEGF-A (-0.63, p=0.005). The expression of NOX4 was parallel to that of plasma TNF-α (0.305, p=0.037), especial-ly in DM. Cumulative mortality at 12-month was related to NLR ≥3 (p=0.019) and TNF-α ≥8.1 (p=0.048). The best cut-off point for NLR to predict mortality was 3.4. Conclusions: NOX4 and TNF-α are crucial for the development and complications of lower limb ischemia, especially in DM. hs-CRP could have a negative influence on angiogenesis too. NLR and TNF-α represent suita-ble markers of mortality in CLTI. These results are novel because they connect muscle gene expres-sion and plasma information in patients with advanced PAD, deepening the search of new and ac-curate targets for this condition.

Effects of Folinic Acid Administration on Lower Limb Ischemia/Reperfusion Injury in Rats

Surgery under ischemic conditions, lasting up to 3 h, is routinely performed in orthopedic surgery, causing undesirable injury due to ischemia-reperfusion syndrome, with short and medium-term functional repercussions. To date, there is no established prophylactic treatment. In this work we evaluated folinic acid (FA) in a rodent model of lower limb ischemia-reperfusion (IRI-LL). 36 male WAG rats underwent 3 h of lower limb ischemia. In the saline group, rats received intraperitoneal administration of saline (used as vehicle for treatment). In the experimental group, rats were pretreated with FA (2.5 mg/kg) before the end of ischemia. After ischemia, animals were sacrificed at 3 h, 24 h or 14 days (for biochemical determination (Na+, K+, Cl-, urea, creatinine, CK, LDH, ALP, ALT, and AST), pathological assessment, or functional study using the rotarod test; respectively). Another six animals were used to establish the reference values. The prophylactic administration of FA significantly reduced the elevation of biochemical markers, especially those that most directly indicate muscle damage (CK and LDH). In addition, it also improved direct tissue damage, both in terms of edema, weight, PMN infiltrate and percentage of damaged fibers. Finally, the administration of FA allowed the animals to equal baseline values in the rotarod test; what did not occur in the saline group, where pre-ischemia levels were not recovered. Following 3 h of lower limb ischemia, FA minimizes the increase of CK and LDH, as well as local edema and leukocyte infiltration, allowing a faster recovery of limb functionality. Therefore, it could be considered as a prophylactic treatment when tourniquet is used in clinics.

Acute leukemia presenting as acute lower limb ischemia

Summary: Objectives: Acute lower limb ischemia (ALLI) is a common vascular emergency. However, ALLI presenting as the initial symptom of acute leukemia (AL) is scarce. Here we present a case of ALLI in the setting of acute myeloid leukemia (AML) while systematically reviewing the current literature to withdraw conclusions about the management, prognosis, and treatment for this atypical presentation of AL. Methods: We conducted a systematic electronic research according to Preferred Reporting Items for Systematic Review and Meta-Analysis protocol (PRISMA) for articles published from January 1981 up to January 2021 concerning ALLI in the setting of acute leukemia (AL). Patients’ baseline characteristics were recorded and nine outcomes of interest were studied. Results: Twenty-six individuals, 16 males with a mean age of 46.3 years (±20) were included in this review. The diagnosis included 13 AML patients (50%), 11 acute promyelotic leukemia (APL) (42.3%) and two acute lymphoblastic leukemias (ALL) (7.7%). Treatment varied among nine different regimens. Four patients were treated with chemotherapy alone (15.4%), four with thrombectomy alone (15.4%), and 11 with a combination of chemotherapy and thrombectomy (42.3%). Eight major amputations were recorded (30. 8%). Thirty-day mortality was 35.7%. Forty-eight peripheral thrombotic events were recorded with 12 patients suffering recurrent thrombotic events. Conclusion: ALLI as the presenting symptom of AL is a rare condition that carries significant mortality and amputation rates. Timely diagnosis is crucial concerning short-term survival and limb salvage. APL, despite being the rarest form of AL, represented a significant proportion of the patient population in this review. The role of leukostasis in the disease’s progression and the efficacy of leukapheresis as a treatment regimen should be further investigated through case-control studies.

Study of lncRNA TUG1/miR-320 in EPC Transplantation to Improve Lower Limb Ischemia and Promote Angiogenesis in Mice

To The aim of the current study was to investigate the changes in lncRNA TUG1/miR-320 and related proteins with ischaemic time in an ischemia model. A nude mouse model of lower limb ischemia was established by ligating the femoral artery, and laser Doppler measurements were used to demonstrate the successful establishment of the ischemia model. The cells were extracted from the bone marrow of nude mice, and the proliferation, migration and vascular-forming ability of the cells were analysed. When transplanted into ischemia model mice, blood flow measurements indicated that EPCs can speed up blood flow recovery. The results of HE staining indicated an improvement in inflammatory damage, and immunohistochemistry revealed an increase in capillaries. RT-PCR and Western blot experiments showed that the improvement of ischemia was related to an increase in lncRNA TUG1 and a decrease in miR-320 and that the expression of the related downstream proteins STAT3, VEGFR-2, Wnt-5a and β-catenin increased gradually. These changes promoted an increase in capillaries, the recovery of blood flow, and the improvement of muscle damage. Therefore, EPC transplantation can improve the inflammatory response of lower limb muscles by increasing the expression of lncRNA TUG1 and thereby accelerate the recovery of ischaemic limbs.