Mitochondrial respiration in peripheral arterial disease depends on stage severity.

Peripheral arterial disease (PAD) is an increasing cause of morbidity and its severity is graded based on clinical manifestation. To investigate the influence of the different stages on myopathy of ischemic muscle we analysed severity-dependent effects of mitochondrial respiration in PAD. Eighteen patients with severe PAD, defined as chronic limb-threatening ischemia, 47 patients with intermittent claudication (IC) and 22 non-ischemic controls were analysed. High-resolution respirometry (HRR) was performed on muscle biopsies of gastrocnemius and vastus lateralis muscle of patients in different PAD stages to investigate different respiratory states. Results from HRR are given as median and interquartile range and were normalized to citrate synthase activity (CSA), a marker for mitochondrial content. In order to account for inter-individual differences between patients and controls, we calculated the ratio of O2-flux in gastrocnemius muscle over vastus muscle ('GV ratio'). CSA of the gastrocnemius muscle as a proxy for mitochondrial content was significantly lower in critical ischemia compared to controls. Mitochondrial respiration normalized to CSA was higher in IC compared to controls. Likewise, the GV ratio was significantly higher in IC compared to control. Mitochondrial respiration and CSA of PAD patients showed stage-dependent modifications with greater changes in the mild PAD stage group (IC).

A Free-Floating Aortic Thrombus: An Uncommon Approach to Handle a Rare Clinical Entity.

BACKGROUND: Thrombotic material in the non-aneurysmatic and non-atherosclerotic aorta is a rare entity without any recommended standard treatment so far. We present a successful treatment strategy for patients who do not fit into any of the common approaches. CASE REPORT: A free-floating thrombus in the descending aorta was found as source of embolism in an 82-year-old female patient with lower limb ischemia. After initial heparinization of the patient without relevant reduction of the thrombotic mass, the thrombus was removed using an interdisciplinary approach. Under echocardiographic guidance to locate the thrombus, the AngioVac device, usually licensed to remove floating thrombi from the venous system, was used off-label to remove the thrombus by a transfemoral approach. To avoid rebuilding of a new thrombus, the attachment point with an exulcerated plaque in the descending aorta was covered by a stent graft via the same femoral access. The patient did not experience any further embolic events, and the postoperative course was uncomplicated. CONCLUSION: Patients with uncommon aortic diseases, such as the reported free-floating thrombus, should be treated by an individualized, interdisciplinary approach. Besides the recommended treatment options, there are other uncommon approaches that might offer an alternative in complex cases. CLINICAL IMPACT: Evidence is rare for the treatment of a free-floating thrombus in the descending aorta and the treatment strategy remains discussed controversially. We present a rather uncommon approach of successful off-label treatment for patients who do not fit into any of the common approaches (operative, endovascular, or conservative treatment based on patient's comorbidities). The AngioVac System has already been successfully used off-label in the arterial system but not in the above presented way of treating a free-floating thrombus in a patient with high embolization risk and treatment-limiting comorbidities.

Comparing the Efficacy of Endovascular Simulation Training in different Training Formats: a randomized controlled trial.

INTRODUCTION: High-fidelity endovascular simulators have demonstrated significant potential in enhancing interventionalists' performance metrics, including procedure time, fluoroscopy time, and contrast volume usage. However, it is less clear whether trainee performance, when assessed using both multidimensional global and procedure-specific rating scales, improves in a manner consistent with these metric parameters. This study aimed to determine whether the structure of the training - conducted in block sessions or weekly intervals - impacts the effectiveness of the training. METHODS: 20 students were enrolled in this prospective, randomized, controlled, single-center trial. They were randomly divided into block and weekly training groups, each undergoing 6 hours of supervised endovascular training on a Mentice simulator over a span of 3 weeks. At the outset and conclusion of their training, students performed a predefined peripheral endovascular intervention, which was assessed by an experienced interventionalist. Furthermore, participants were prompted to complete a survey at both the beginning and the end of the study. RESULTS: Both groups exhibited significant improvements in procedure time, fluoroscopy time, contrast volume usage, global rating scale scores, and performance-specific rating scale scores. However, no significant difference was observed between the two groups. The simulator training notably boosted the trainee's self-confidence. CONCLUSION: Simulator training not only enhances metric performance parameters, but also improves performance as assessed by both global rating scale and procedure-specific rating scale. Whether the training is conducted in block sessions or weekly intervals did not affect its efficacy. As such, the training format can be tailored to best fit the specific circumstances and setting.

Study Protocol of a Prospective Multicenter Observational Study Evaluating Acute Lower Limb Ischemia.

INTRODUCTION: Acute lower limb ischemia (ALI) is a limb- and potentially life-threatening condition which requires urgent evaluation and treatment. Contemporary data on optimal therapy and prognosis of ALI are lacking, while surgical, hybrid, and foremost endovascular techniques have rapidly evolved over the past decades. Available clinical guidelines are not based on high-level evidence and do not fully reflect day-do-day practice. Contemporary data on etiology, procedural strategies as well as patient outcomes in ALI are urgently needed to improve care and prevent limb loss. The current study was initiated by the European Vascular Research Collaborative (EVRC), established by young European vascular specialists, and aims to provide insight into contemporary treatment strategies in ALI and its clinical results within Europe. In this manuscript we report the rationale and a detailed study protocol. MATERIAL AND METHODS: The proposed study is a prospective, international, multicenter, observational study on ALI (PROMOTE-ALI) (ClinicalTrials.gov - NCT05138679). Patients with ALI (Rutherford classification grade I -III) of one or both lower extremities will be included in the study. The primary endpoint of the study is amputation-free survival (AFS) at 30 d. Secondary endpoints are freedom from target limb reintervention, freedom from complications, clinical outcome of the index leg, and limb salvage and survival at 30 and 90 d after diagnosis of ALI. CONCLUSIONS: ALI remains a challenging condition and due to the heterogeneous etiology, clinical presentation and treatment strategies, a large multicenter study on this topic is needed to gain contemporary data on clinical outcomes and prognosis, especially for modern endovascular techniques. PROMOTE-ALI is expected to provide these data and set a benchmark for future randomized controlled trials (RCTs).

Comparison of Prosthetic and Vein Bypass with Nitinol Stents in Long Femoropopliteal Lesions.

BACKGROUND: Guidelines for the treatment of long femoropopliteal lesions are not based on a high level of evidence and recent randomized controlled trials (RCTs) challenge vein bypass (VBP) as the recommended therapy. This study compared prosthetic (PTFE) bypass, VBP and angioplasty with nitinol stents in long femoropopliteal lesions. METHODS: Pooled data from a RCT and a retrospective database with the same inclusion criteria were analyzed with primary and secondary patency as well as freedom from target lesion revascularization (TLR) as primary endpoints. RESULTS: Between 2016 and 2018 a total of 172 lesions were treated in three groups (PTFE: n = 62, VBP: n = 55, stent: n = 55). Clinical and lesion characteristics were similar with mean lesion lengths between 260 and 279mm. Technical success rate in the stent group was 87%. There were no significant differences between the groups in patency rates, freedom from TLR, limb salvage and survival during 2-year follow-up. The primary patency rates for the PTFE, VBP and stent groups were 50%, 56% and 60% at 2 years. The PTFE group had significantly less complications compared to the other groups and a shorter hospital-stay compared to the VBP group. Clinical improvement was significantly better in the PTFE and VBP group compared to the stent group. CONCLUSIONS: The 2-year results indicate that the role of VBP as the recommended therapy for long femoropopliteal lesions may not be unchallenged due to the similar results in all three groups. Further RCTs are needed to determine the best revascularization modality for long femoropopliteal lesions.

Long-Term Results of Endovascular Treatment with Nitinol Stents for Femoropopliteal TASC II C and D Lesions.

Background and Objectives: The feasibility of endovascular treatment (EVT) for Trans-Atlantic Inter-Society Consensus (TASC) II C and D femoropopliteal artery lesions has been described, but no prospective study has performed a long-term follow-up. The aim of this study was to report the long-term results of nitinol stents (NS) for the treatment of long femoropopliteal lesions. Materials and Methods: A single-center prospective, randomized controlled trial (RCT) comparing EVT with NS and vein bypass surgery was previously performed. The EVT group's follow-up was extended and separately analyzed with primary patency as the primary endpoint. The secondary endpoints were technical success, secondary patency, reinterventions, limb salvage, survival, complications, and clinical improvement. Results: Between 2016 and 2020, 109 limbs in 103 patients were included. A total of 48 TASC II C and 61 TASC II D lesions with a mean lesion length of 264 mm were reported. In 53% of limbs, the indication for treatment was chronic limb-threatening ischemia. The median follow-up was 45 months. Technical success was achieved in 88% of cases, despite 23% of the lesions being longer than 30 cm (retrograde popliteal access in 22%). At four-year follow-up, primary patency, secondary patency, and freedom from target lesion revascularizations were 35%, 48%, and 58%, respectively. Limb salvage and survival were 90% and 80% at 4 years. Clinical improvement of at least one Rutherford category at the end of follow-up was achieved in 83% of limbs. Conclusions: This study reports the longest follow-up of endovascular treatment with nitinol stents in femoropopliteal TASC II C and D lesions. The results emphasize the feasibility of an endovascular-first strategy, even in lesions beyond 30 cm in length, and clarify its acceptable long-term durability and good clinical outcomes. Large multicenter RCTs with mid- and long-term follow-up are needed to investigate the role of different endovascular techniques in long femoropopliteal lesions.

The effect of revascularization on recovery of mitochondrial respiration in peripheral artery disease: a case control study.

BACKGROUND: Peripheral arterial disease (PAD) is accompanied by myopathy characterized by mitochondrial dysfunction. The aim of this experimental study was to investigate the effect of revascularization procedures on mitochondrial function in ischemic and non-ischemic muscle. METHODS: Muscle biopsies from patients with symptomatic stage IIB/III PAD caused by isolated pathologies of the superficial femoral artery were obtained from muscle regions within the chronic ischemic muscle (gastrocnemius) and from non-ischemic muscle (vastus lateralis) before and 6 weeks after invasive revascularization. High-resolution respirometry was used to investigate mitochondrial function and results were normalized to citrate synthase activity (CSA). Results are given in absolute values and fold over basal (FOB). RESULTS: Respiratory states (OXPHOS (P) and electron transfer (E) capacity) normalized to CSA decreased while CSA was increased in chronic ischemic muscle after revascularization. There were no changes in in non-ischemic muscle. The FOB of chronic ischemic muscle was significantly higher for CSA (chronic ischemic 1.37 (IQR 1.10-1.64) vs. non-ischemic 0.93 (IQR 0.69-1.16) p = 0.020) and significantly lower for respiratory states normalized to CSA when compared to the non-ischemic muscle (P per CSA chronic ischemic 0.64 (IQR 0.46-0.82) vs non-ischemic 1.16 (IQR 0.77-1.54) p = 0.011; E per CSA chronic ischemic 0.61 (IQR 0.47-0.76) vs. non-ischemic 1.02 (IQR 0.64-1.40) p = 0.010). CONCLUSIONS: Regeneration of mitochondrial content and function following revascularization procedures only occur in muscle regions affected by malperfusion. This indicates that the restoration of blood and oxygen supply are important mediators aiding mitochondrial recovery.

The Role of Mitochondrial Function in Peripheral Arterial Disease: Insights from Translational Studies.

Recent evidence demonstrates an involvement of impaired mitochondrial function in peripheral arterial disease (PAD) development. Specific impairments have been assessed by different methodological in-vivo (near-infrared spectroscopy, 31P magnetic resonance spectroscopy), as well as in-vitro approaches (Western blotting of mitochondrial proteins and enzymes, assays of mitochondrial function and content). While effects differ with regard to disease severity, chronic malperfusion impacts subcellular energy homeostasis, and repeating cycles of ischemia and reperfusion contribute to PAD disease progression by increasing mitochondrial reactive oxygen species production and impairing mitochondrial function. With the leading clinical symptom of decreased walking capacity due to intermittent claudication, PAD patients suffer from a subsequent reduction of quality of life. Different treatment modalities, such as physical activity and revascularization procedures, can aid mitochondrial recovery. While the relevance of these modalities for mitochondrial functional recovery is still a matter of debate, recent research indicates the importance of revascularization procedures, with increased physical activity levels being a subordinate contributor, at least during mild stages of PAD. With an additional focus on the role of revascularization procedures on mitochondria and the identification of suitable mitochondrial markers in PAD, this review aims to critically evaluate the relevance of mitochondrial function in PAD development and progression.

Regeneration of Mitochondrial Function in Gastrocnemius Muscle in Peripheral Arterial Disease After Successful Revascularisation.

OBJECTIVE: Myopathy, characterised by altered mitochondrial function, is a central part of the pathophysiology of peripheral arterial disease and the aim of this study was to investigate the effect of revascularisation on mitochondrial function. METHODS: High resolution respirometry was used to investigate mitochondrial respiration and the results were normalised to citrate synthase activity (CSA), a marker of mitochondrial content. Ten patients with symptomatic peripheral arterial disease (study group) and 10 subjects without ischaemia (control group) were included. Ankle brachial index and ultrasound imaging were performed before and after vascular intervention to confirm technically successful revascularisation. Within the study group, muscle biopsies from the gastrocnemius muscle were taken before vascular intervention and six weeks after revascularisation. Within the control group, tissue was harvested once. RESULTS: There were no significant group differences regarding anthropometric data. CSA showed a significant increase after successful revascularisation (CSA pre-operative 281.4 (252.4-391.8) nmol/min/mg protein vs. CSA post-operative 438.5 (361.4-471.3) nmol/min/mg protein; p = .01) with post-operative return of values to the range of control subjects (CSA control 396.6 (308.2-435.9)). Mitochondrial respiration normalised to CSA in oxidative phosphorylation (P) as well as in electron transfer (E) capacity were significantly reduced post-operatively when compared with pre-operative values (P pre-operative 0.218 (0.196-0.266) pmol/(sec×mg) per CSA vs. post-operative 0.132 (0.116-0.150) pmol/(sec×mg) per CSA, p = .007; E pre-operative 0.230 (0.195-0.279) pmol/(sec×mg) per CSA vs. post-operative 0.129 (0.120-0.154) pmol/(sec×mg) per CSA, p = .005) meaning a post-operative return of values to within the range of control subjects (P control 0.124 (0.080-0.155) pmol/(sec×mg) per CSA; E control 0.121 (0.079-0.125) pmol/(sec×mg) per CSA). CONCLUSION: With these results, it has been shown that the initially impaired mitochondrial function and content can normalise after revascularisation.

Aortic Foreign Body Caused by Rupture of Endobag after EVAS Using the Nellix Aneurysm Sealing System-A Case Report.

The Nellix aneurysm sealing system aims at sealing the cavity of the sac of the aneurysm, to reduce typical complications such as migration or endoleak. We report on a case of a unique device-associated complication: rupture and displacement of the filling material into the aortic lumen, causing peripheral ischemia and imminent renal and visceral occlusion, in a patient with anastomotic ulcer after an open aortobiiliac bypass and calcified and tortuous iliac arteries. The material was removed by open surgery. The patient recovered completely. The device should be handled with great caution in cases with hostile access routes, and in secondary interventions.

Treatment options of crural pseudoaneurysms.

BACKGROUND: Pseudoaneurysms (PAs) of crural arteries represent rare complications of vascular interventions or surgery. Management of crural PAs includes different treatment options, conservative treatment as well as open surgery or endovascular procedures. We reviewed our experience. PATIENTS AND METHODS: We retrospectively analysed all patients who were diagnosed with crural PAs since 2003. We evaluated etiology, treatment and outcome. Endpoints were target vessel patency, vascular re-intervention and limb loss. RESULTS: A total of 30 patients were diagnosed with crural PAs. PA was caused by vascular intervention in 27 patients (90 %): open balloon thrombectomy (n = 25), subfascial endoscopic perforator vein surgery (n = 1) and transcutaneous catheter-assisted thrombus aspiration (n = 1). In 3 patients (10 %) it was caused by orthopaedic surgical procedures. Location of crural PAs were peroneal artery (n = 11; 36.7 %), posterior tibial artery (n = 10; 33.3 %), anterior tibial artery (n = 5; 16.7 %), and tibioperoneal trunk (n = 4; 13.3 %). Treatment of crural PAs included open surgery (n = 3; 10 %), endovascular procedures (n = 13; 43.3 %) such as endograft implantation (n = 9) or coil embolisation (n = 4), and conservative management (n = 14; 46.7 %). After a median follow-up period of 7 months (range: 0 - 46 months) 8 of 9 endografts were occluded, in none of these patients a minor or a major amputation was necessary. None of the surgically, endovascularly and conservatively treated patients needed a re-intervention for crural PA. A major amputation was necessary in 4 patients due to progression of peripheral arterial disease; none was a directly consequence of the crural PA. CONCLUSIONS: Crural PAs are mainly caused by vascular intervention, most frequently by catheter thrombectomy. As a consequence, we recommend fluoroscopic-assisted balloon thrombectomy over a guide wire as routine technique. In many cases of crural PAs, conservative management is sufficient. The choice of treatment of crural PAs depends on size, location and associated symptoms. Endovascular treatment using endografts is limited by poor long-term patency.

Incidence and treatment of local stenosis or occlusion at the vascular access site leading to limb ischemia and new-onset intermittent claudication after percutaneous interventions: implications of vascular closure devices.

OBJECTIVE: Vascular access site complications (ASCs) are an ongoing hazard of percutaneous interventions (PI). We analyzed incidence, indication, and results of operative repair of access site complications leading to acute limb ischemia (ALI) or new-onset severe claudication (CI) in our institution during an 8-year period. METHODS: Retrospective analysis: demographic parameters, details of coronary or vascular intervention, use of a vascular closure device (VCD), clinical presentation, diagnosis and therapy. ENDPOINTS: perioperative outcome (death, limb loss, and need for re-operation/intervention) and length of hospital stay. For comparison of annual operation rates, patients were grouped by the years 2001 to 2004 (no use of VCD) and 2005 to 2008 (selective use of a VCD; in all cases: Angio-Seal), and Chi-Square-test was applied. RESULTS: Fifty-one patients (19 female; median age: 64.5 years) underwent repair of arterial ASCs causing ALI (n = 32) or new-onset severe CI (n = 19) after 58,453 catheter interventions (overall rate: 0.087%; ALI: 0.055%; CI: 0.032%). Corresponding with more widespread VCD use, the annual number of ALI and new onset CI increased significantly (P < 0.001). PERIOPERATIVE OUTCOME: 30 day mortality was 4%. No limb loss occurred. Re-operations were indicated in 10 patients (20%) for: hematoma (n = 5), local infection (n = 3), revision of fasciotomy (n = 1), and repeated thrombectomy (n = 1). Median length of postoperative hospital stay: 7 days (range: 1-28). CONCLUSION: ALI and new-onset severe CI due to access site complications after PI are rare, however, they are potentially threatening life and limb. The use of VCDs results in an overall increase of ischemic complications.

[Establishment of a new research concept at a university location]. / Die Etablierung eines neuen Forschungskonzepts an einem universitären Standort.

Apart from daily clinical work and patient care, research and student teaching are essential assignments of a university hospital. The implementation of a completely new research laboratory at the Department of Vascular Surgery at the Medical University of Innsbruck led to the creation of a novel infrastructure for the design and set-up of a newly founded research focus. The cooperation with national as well as international research collaborators was essential for this process. The construction of a research network is not only important for the design and conception of a new research laboratory but also for the development of new study protocols and exchange and discussion of results. After the successful implementation of Experimental Vascular Surgery in Innsbruck, the realization of basic research projects as well as translational research projects is possible at this university location. Moreover, simulation training is an emerging field of research that aims to add more realistic surgical skills to residency programs, attract future residents and teach more complex novel techniques.

Neuronal Pre- and Postconditioning via Toll-like Receptor 3 Agonist or Extracorporeal Shock Wave Therapy as New Treatment Strategies for Spinal Cord Ischemia: An In Vitro Study.

Spinal cord ischemia (SCI) is a devastating and unpredictable complication of thoracoabdominal aortic repair. Postischemic Toll-like receptor 3 (TLR3) activation through either direct agonists or shock wave therapy (SWT) has been previously shown to ameliorate damage in SCI models. Whether the same applies for pre- or postconditioning remains unclear. In a model of cultured SHSY-5Y cells, preconditioning with either poly(I:C), a TLR3 agonist, or SWT was performed before induction of hypoxia, whereas postconditioning treatment was performed after termination of hypoxia. We measured cytokine expression via RT-PCR and utilized Western blot analysis for the analysis of signaling and apoptosis. TLR3 activation via poly(I:C) significantly reduced apoptotic markers in both pre- and postconditioning, the former yielding more favorable results through an additional suppression of TLR4 and its downstream signaling. On the contrary, SWT showed slightly more favorable effects in the setting of postconditioning with significantly reduced markers of apoptosis. Pre- and post-ischemic direct TLR3 activation as well as post-ischemic SWT can decrease apoptosis and proinflammatory cytokine expression significantly in vitro and might therefore pose possible new treatment strategies for ischemic spinal cord injury.

The Mangled Extremity Severity Score (MESS) does not predict amputation in popliteal artery injury.

PURPOSE: Vascular injuries in lower extremity trauma, especially with involvement of the popliteal artery, are associated with considerably high rates of limb loss, especially with blunt trauma mechanisms. The aim of this study was to evaluate the risk of amputation in patients with traumatic popliteal artery lesions with special focus on the validity of the Mangled Extremity Severity Score (MESS). METHODS: In this retrospective study, all patients treated for isolated lesions of the popliteal artery following trauma between January 1990 and December 2020 at a high-volume level I trauma center were included. Primary outcome was limb salvage dependent on MESS and the influence of defined parameters on limb salvage was defined as secondary outcome. The extent of trauma was assessed by the MESS. RESULTS: A total of 50 patients (age 39.2 ± 18.6 years, 76% male) with most blunt injuries (n = 47, 94%) were included. None of the patients died within 30 days and revascularization was attempted in all patients with no primary amputation and the overall limb salvage rate was 88% (44 patients). A MESS ≥ 7 was observed in 28 patients (56%) with significantly higher rates of performed fasciotomies (92.9% vs. 59.1%; p < 0.01) in those patients. MESS did not predict delayed amputation within our patient cohort (MESS 8.4 ± 4.1 in the amputation group vs. 8.1 ± 3.8 in the limb salvage group; p = 0.765). CONCLUSION: Revascularization of limbs with isolated popliteal artery injuries should always be attempted. MESS did not predict delayed amputation in our cohort with fasciotomy being an important measure to increase limb salvage rates.

Risk factors for major amputation after arterial vascular trauma of the lower extremity.

BACKGROUND & OBJECTIVE: Arterial vascular trauma bears a great risk of poor functional outcome or limb loss. The aim of this study was to analyze amputation rates of patients after vascular trauma and to perform a predictor analysis for the risk of major amputation. METHODS: In a single-center retrospective analysis of 119 extremities treated for arterial vascular injury between 1990 and 2018 amputation rates and factors associated with limb loss were assessed. All patients were treated for traumatic vascular injuries; iatrogenic injuries were not included in the study. RESULTS: During the study period, a total of 119 legs in 118 patients were treated after arterial vascular trauma. The in-hospital major amputation rate was 16.8% and the mortality rate was 2.5%. In the predictors analysis, vascular re-operation (amputation rate 53.8% vs 12%, odds ratio = 8.56), a Rutherford category ⩾IIb (25.4% vs 4.2%, odds ratio = 6.43), work-related or traffic accidents (28.2% vs 0%, odds ratio = 4.86), concomitant soft tissue or bone injuries (26.7% vs 7.3%, odds ratio = 4.64), polytrauma (33.3% vs 12%, odds ratio = 3.68), and blunt trauma (18.9% vs 0% for penetrating trauma, odds ratio = 1.64) were found to be associated with amputation. CONCLUSIONS: Lower extremity arterial vascular trauma was associated with a significant major amputation rate. Several predictors for limb loss were identified, which could aid in identifying patients at risk and adapting their treatment.

A Modified Run-Off Resistance Score from Cross-Sectional Imaging Discriminates Chronic Critical Limb Ischemia from Intermittent Claudication in Peripheral Arterial Disease.

Atherosclerotic peripheral arterial disease (PAD) leads to intermittent claudication (IC) and may progress into chronic limb-threatening ischemia (CLTI). Scoring systems to determine the atherosclerotic burden of a diseased extremity have been developed. This study aimed to evaluate a modification of the run-off resistance (mROR) score for its usability in cross-sectional imaging. The mROR was determined from preoperative imaging of patients undergoing revascularization for PAD. A total of 20 patients with IC and 20 patients with CLTI were consecutively included. A subgroup analysis for diabetic patients was conducted. The mROR was evaluated for its correlation with disease severity and clinical covariates. Patients with CLTI were older; cardiovascular risk factors, diabetes, and ASA 4 were more frequent. The mROR scores were higher in CLTI than in IC. In diabetic patients, no difference was detected between CLTI and IC. In CLTI, non-diabetic patients had a higher mROR. The mROR score is positively correlated with the severity of PAD and can discriminate CLTI from IC. In diabetic patients with CLTI, the mROR is lower than in non-diabetic patients. The mROR score can be determined from cross-sectional imaging angiographies. It may be useful for clinicians helping with vascular case planning, as well as for scientific purposes.