Multiparametric ultrasound evaluation with CEUS and shear wave elastography for carotid plaque risk stratification.

PURPOSE: To assess the diagnostic effectiveness of Multiparametric ultrasound (MPUS), which includes color Doppler ultrasound (CDUS), CEUS and Shear wave elastography (SWE), for evaluating carotid plaque as compared with CT-angiography (CTA) and histology. MATERIALS AND METHODS: Forty-three consecutive patients scheduled to undergo carotid endarterectomy underwent MPUS. Then, after periods ranging from 2 days to 2 weeks, all underwent CTA. Each plaque was classified by means of dedicated scores for CEUS and SWE as compared with CTA features. At surgery, each plaque was removed in a single fragment to facilitate histological analysis, which evaluated 4 features: extension of the lipid core, thickness of the fibrous cap, inflammatory infiltrate (CD68 + and CD3 + markers) and the presence of intraplaque microvessels. For the CEUS, SWE and CTA, the following values for identifying plaque vulnerability were evaluated: sensitivity, specificity, accuracy, negative predictive value (NPV), positive predictive value (PPV) and Area under the curve (AUC). Cohen's kappa was used to evaluate the concordance between measurements in the different imaging methods. A p < 0.05 was considered statistically significant. RESULTS: At histology, 31 out of 43 plaques were identified as vulnerable because of the presence of at least one of the following criteria: fibrous cap < 200 µm, lipid core, intraplaque hemorrhage, inflammatory infiltrate or intraplaque neovascularization. CTA showed a sensitivity of 87.1%, a specificity of 100%, a PPV of 100%, an NPV of 75% and an AUC of 93.5%. SWE showed a sensitivity of 87.1%, a specificity of 66.7%, a PPV of 87.1%, an NPV of 66.7% and an AUC of 76.9%. CEUS showed a sensitivity of 87.1%, a specificity of 58.3%, a PPV of 84.4%, an NPV of 63.6% and an AUC of 72.7%. CONCLUSIONS: Multiparametric ultrasound is an effective modality to obtain comprehensive information on carotid plaques. Further studies are needed to determine whether it can be considered a diagnostic standard.

What is the role of contrast-enhanced ultrasound in the evaluation of the endoleak of aortic endoprostheses? A comparison between CEUS and CT on a widespread scale.

OBJECTIVE: To evaluate the accuracy of contrast-enhanced ultrasound (CEUS) in comparison to CT angiography (CTA) to identify and classify endoleaks following abdominal aortic aneurism repair with endoprosthesis. MATERIALS AND METHODS: A retrospective analysis of 181 patients treated with EVAR, from September 2009 to September 2014, was performed. Patients were evaluated with CEUS, CTA and angiography in the cases requiring treatment. Sac diameter, sac integrity, identification and classification of endoleaks were taken into consideration. Sensitivity, specificity, accuracy and negative predictive values were considered for each modality of endoleak identification. RESULTS: Forty-two endoleaks (23.2%; type II: 39 cases, type III: 3 cases) were documented. Sensitivity and specificity of CEUS and CT were, respectively, 97.6 and 90.5, 100 and 100%. In two cases, CEUS was able to better classify endoleaks compared to CT. CONCLUSIONS: CEUS accuracy to identify endoleaks following EVAR is similar to CT. CEUS should be considered as an effective modality for the long-term surveillance of EVAR because of its capability to correctly classify endoleaks with no ionizing radiation exposure.

Halting pro-survival autophagy by TGFß inhibition in bone marrow fibroblasts overcomes bortezomib resistance in multiple myeloma patients.

Bortezomib (bort) has improved overall survival in patients with multiple myeloma (MM), but the majority of them develop drug resistance. In this study, we demonstrate that bone marrow (BM) fibroblasts (cancer-associated fibroblasts; CAFs) from bort-resistant patients are insensitive to bort and protect the RPMI8226 and patients' plasma cells against bort-induced apoptosis. Bort triggers CAFs to produce high levels of interleukin (IL)-6, IL-8, insulin-like growth factor (IGF)-1 and transforming growth factor (TGF) ß. Proteomic studies on CAFs demonstrate that bort resistance parallels activation of oxidative stress and pro-survival autophagy. Indeed, bort induces reactive oxygen species in bort-resistant CAFs and activates autophagy by increasing light chain 3 protein (LC3)-II and inhibiting p62 and phospho-mammalian target of rapamycin. The small-interfering RNA knockdown of Atg7, and treatment with 3-methyladenine, restores bort sensitivity in bort-resistant CAFs and produces cytotoxicity in plasma cells co-cultured with CAFs. In the syngeneic 5T33 MM model, bort-treatment induces the expansion of LC3-II(+) CAFs. TGFß mediates bort-induced autophagy, and its blockade by LY2109761, a selective TßRI/II inhibitor, reduces the expression of p-Smad2/3 and LC3-II and induces apoptosis in bort-resistant CAFs. A combination of bort and LY2109761 synergistically induces apoptosis of RPMI8226 co-cultured with bort-resistant CAFs. These data define a key role for CAFs in bort resistance of plasma cells and provide the basis for a novel targeted therapeutic approach.

Statins reduce levels of metalloproteinases in patients with carotid occlusive disease.

AIM: Pharmaceutical stabilization of an unstable low-grade carotid artery stenosis delays surgery and improve outcome. Statins can be used to reduce intimal media thickness. Our aim was to determine the clinical and biological effects of rosuvastatin on plaque stabilization or regression. METHODS: Forty-two consecutive male patients presenting with an asymptomatic internal carotid artery plaque uniformly anechogenic (group 1) 40-50% lumen diameter reduction formed the basis of the study. A group of 35 patients affected with a uniformly echogenic carotid artery stenosis (40-50%) served as control (group 2). Patients were followed-up every 8-month for 2 years with B-mode ultrasonography and color imaging. A computed tomography angiography (CTA) was performed before the initiation of the study period and at the end to confirm plaque characteristics and the degree of stenosis. Ticlopidine (250 mg/day) and rosuvastatin (10 mg/day) were administered. One blood sample was drawn at every control to assess the release of matrix metallopoteinases (MMPs)-1, -2, -3, -9, tissue inhibitors of metalloproteinases (TIMPs)-1 and -2. RESULTS: After the administration of rosuvastatin plasma level of MMP-1, -2, -3 and -9 significantly decreased in both groups (P<0.001). Conversely, plasma level of TIMP-1 and -2 significantly increased in both groups (P<0.001). B-mode ultrasonography and color imaging and CTA failed to demonstrate a stabilization or regression of uniformly anehogenic carotid plaque during follow-up. CONCLUSION: Rosuvastatin decreases the plasma level of MMPs and increases those of TIMPs. However, neither progression nor stabilization of low-grade unstable carotid plaques was seen.

Bone marrow fibroblasts parallel multiple myeloma progression in patients and mice: in vitro and in vivo studies.

The role of cancer-associated fibroblasts (CAFs) has not been previously studied in multiple myeloma (MM). Here, cytofluorimetric analysis revealed higher proportions of bone marrow (BM) CAFs in patients with active MM (both at diagnosis and relapse) compared with patients in remission or those with monoclonal gammopathy of undetermined significance or deficiency anemia (controls). CAFs from MM patients produced increased levels of transforming growth factor-ß, interleukin-6, stromal cell-derived factor-1α, insulin-like growth factor-1, vascular endothelial growth factor and fibroblast growth factor-2 and displayed an activated and heterogeneous phenotype, which supported their origin from resident fibroblasts, endothelial cells and hematopoietic stem and progenitor cells via the endothelial-mesenchymal transition as well as mesenchymal stem cells via the mesenchymal transition, as both of these processes are induced by MM cells and CAFs. Active MM CAFs fostered chemotaxis, adhesion, proliferation and apoptosis resistance in MM cells through cytokine signals and cell-to-cell contact, which were inhibited by blocking CXCR4, several integrins and fibronectin. MM cells also induced the CAFs proliferation. In syngeneic 5T33MM and xenograft mouse models, MM cells induced the expansion of CAFs, which, in turn, promoted MM initiation and progression as well as angiogenesis. In BM biopsies from patients and mice, nests of CAFs were found in close contact with MM cells, suggesting a supportive niche. Therefore, the targeting of CAFs in MM patients may be envisaged as a novel therapeutic strategy.

Ultra-low profile Ovation device: is it the definitive solution for EVAR?

When Juan Parodi implanted an endograft in a human body for the first time on September 7, 1990 in Buenos Aires, Argentina, the delivery system of the handmade device was primitive, extremely rigid, and had a bulky profile of 27 French (F). Since then, stent-graft technology has evolved rapidly, limitations of earlier-generation devices have been overtaken, and endovascular aneurysm repair (EVAR) eligibility has increased enormously. Nevertheless (still) challenging aortoiliac anatomy such as short and complex proximal aortic neck seal zones and narrow access vessels are responsible for EVAR ineligibility in up to 50% of cases. The Ovation Prime abdominal stent-graft system (TriVascular, Inc., Santa Rosa, CA, USA) is a trimodular device designed with the aortic body delivered via a flexible, hydrophilic-coated, ultra-low profile catheter (14-F outer diameter - OD). The aortic body is provided with a suprarenal nitinol stent with anchors that provide active fixation, while a network of rings and channels that are inflated with a low-viscosity radiopaque polymer during stent-graft deployment, provides effective sealing. The previous EVAR technology aimed to both anchor and seal using stents combined with fabric, with neither optimized for their roles and each forced to compete for the same space within their delivery catheters, which inevitably led to larger profile of the delivery system. The technical revolution of the Ovation endograft includes the idea to truly uncouple the stages of stent-graft fixation and seal during the procedure. In the Ovation endograft platform, stent and fabric are not competing the same space within the delivery system and an ultra-low profile delivery can be achieved without compromise. With such a low-profile delivery catheter, approximately 90% of men and 70% of women with abdominal aortic aneurysm have access vessel diameters considered fit for endovascular repair. The aim of this review paper was to analyze the main properties of Ovation endograft, to emphasize the advantage of the ultra-low profile device, and to sum up current literature.

MMP and TIMP alterations in asymptomatic and symptomatic severe recurrent carotid artery stenosis.

OBJECTIVES: This study aimed to determine whether the plasma levels of matrix metalloproteinases (MMPs)-2 and -9 and their specific inhibitors (tissue inhibitors of metalloproteinases (TIMPs-1 and -2)) were altered in patients with symptomatic and asymptomatic, severe, recurrent carotid artery stenosis. PATIENTS: Fifty-two patients (out of a total of 621) who had undergone successful carotid artery endarterectomy (CEA) between 1999 and 2003 and developed recurrent carotid artery stenosis (>/=70%) were included in the study. Restenosis was symptomatic in 23 patients and asymptomatic in 29 patients. METHODS: Recurrent carotid artery stenosis was classified based on presentation, and as early-intermediate (6 months to 3 years) or late (>3 years). A detailed clinical history was taken and two blood samples were drawn from each patient to determine plasma levels of MMPs and TIMPs along with other biological parameters. Recurrent stenosis was confirmed with computed tomographic angiography. RESULTS: Patients with symptomatic restenosis had significantly (p<0.001) higher active MMP-2 and -9 plasma values and significantly (p<0.001) lower TIMP-1 and -2 plasma values when compared to patients with asymptomatic restenosis. Plasma concentrations of active MMPs were higher and TIMPs lower in patients affected with late recurrent stenosis as compared to early-intermediate restenosis (p<0.001). No differences were recorded in latent MMP plasma values. Multivariate analysis showed that active MMP-2 and -9 were independent predictors of late recurrent carotid artery stenosis (p<0.03 and p<0.001, respectively). CONCLUSIONS: Higher plasma concentrations of active MMP-2 and -9 were associated with an increased risk of carotid restenosis with plaque recurrence.

Amebic liver abscess: report of three cases.

Amebic abscess is a common manifestation of extraintestinal amebiasis and it is associated with relatively high morbidity and mortality. We present three cases seen in Bari, Southern Italy, one of which was autochthonous and the other two were not. Diagnosis was performed by elevated antibody titre for E. histolytica through immunofluorescence assay and positive antigen determination by ELISA in stools and in abscess aspirate. Fever often accompanied by chills, abdominal pain, weight loss and hepatomegaly were present. Laboratory findings also revealed leukocytosis with neutrophilia. Pleural effusion was observed in two patients. In all our patients multiple abscesses were observed. All the patients were treated with metronidazole and two of them also underwent the aspiration of the amoebic abscess. In all of them there was improvement of the clinical picture, as demonstrated by computerized tomography.

An unusual case of synovial cyst of the hip joint presenting as femoral vein compression and severe lower limb edema.

INTRODUCTION: Synovial cyst of the hip joint causing the compression of the femoral vein is a rare occurrence. We carefully reviewed the international literature collecting 26 additional cases. REPORT: A case of a patient affected with synovial cyst of the hip joint causing the compression of the femoral vein and severe lower limb edema is presented. DISCUSSION: The treatment of choice of synovial cyst compressing the femoral vein is surgical removal.

Basic fibroblast growth factor mediates carotid plaque instability through metalloproteinase-2 and -9 expression.

OBJECTIVE(S): We hypothesized that basic fibroblast growth factor (bFGF) may exert a role in carotid plaque instability by regulating the expression of matrix metalloproteinases (MMP). METHODS: Plaques obtained from 40 consecutive patients undergoing carotid endarterectomy were preoperatively classified as soft or hard. Serum bFGF was pre- and postoperatively measured. The release of MMP-2 and MMP-9 in the blood serum, and the activity, production and expression in the carotid specimens was analyzed. Specific anti-bFGF inhibition tests were performed in vitro on human umbilical artery smooth muscle cells (HUASMC) to evaluate the role of bFGF in the activity, production and expression of MMP-2 and -9. RESULTS: Twenty-one (53%) patients had a soft carotid plaque and 19 (48%) a hard plaque. Preoperative bFGF serum levels were higher in patients with soft plaques [soft=34 (28-39) pg/mL and hard=20 (17-22) pg/mL-p<0.001] and postoperatively returned to normal values (when compared to 10 healthy volunteers). The serum levels of MMP-2 in patients' with soft plaques were higher than those in patients' with hard plaques [soft=1222 (1190-1252) ng/mL and hard=748 (656-793)ng/mL-p<0.0001]. MMP-9 serum values were 26 (22-29) ng/mL for soft plaques and 18 (15-21) ng/mL for hard plaques (p<0.0001). We found increased activity, production and expression of MMP-2 and -9 in soft plaques compared to hard plaques (p<0.001). In vitro inhibition tests on HUASMC showed the direct influence of bFGF on the activity, production and expression of MMP-2 and -9 (p<0.001). CONCLUSIONS: bFGF seems to exert a key role in carotid plaque instability regulating the activity, production and expression of MMP thus altering the physiologic homeostasis of the carotid plaque.

Comparison of femorofemoral and aortofemoral bypass for aortoiliac occlusive disease.

BACKGROUND: Role and results of femorofemoral bypass grafting, usually reserved to high-risk patients affected with unilateral iliac artery occlusion, are still debated. EXPERIMENTAL DESIGN: retrospective clinical study. SETTINGS: University Hospital. PATIENTS: seventy-six high-risk patients (group 1) who underwent a primary expanded polytetrafluoroethylene (ePTFE) externally supported femorofemoral bypass graft were retrospectively compared to two additional groups of patients selected from the entire series of patients who underwent an aortobifemoral bypass graft. Patients of group 2 (n=80) were randomly chosen to determine differences in risk factors, associated diseases, previous abdominal operations, operative indications, preoperative findings and outcome. Patients of group 3 (n=50) were matched for sex, risk factors, associated diseases, previous abdominal operations, operative indications and preoperative findings with those of group 1 to assess the importance of the type of operation in determining the outcome of the procedure. RESULTS: Postoperative mortality (6, 4 and 6%, respectively), 5-year primary and secondary patency (71, 80, 83% and 80, 87, 87%, respectively) and limb salvage rates (78, 87 and 87%, respectively) were similar among the groups (p=NS, p=NS, p=NS, respectively). Five-year survival rate of group 2 was significantly better than that of group 1 and 3 (p<0.04 and p<0.04, respectively). CONCLUSIONS: Primary ePTFE externally supported femorofemoral bypass graft in high-risk patients is safe and produces long-term results similar to aortofemoral reconstruction.

[Inflammatory aneurysm of the abdominal aorta. Study of 355 patients with aortic aneurysm]. / Aneurisma infiammatorio dell'aorta addominale. Studio su 355 portatori di aneurisma aortico.

The Authors report their experience in the treatment of inflammatory aneurysm, on a whole of 355 patients consecutively operated on for abdominal aortic aneurysm. The incidence was 5.6% when relying on clinical aspects; 10.6% when considering the results of microscopy. All patients were operated on through a retroperitoneal approach: early and late results of surgery were not significantly different between the two groups of patients (inflammatory aneurysm 38, atherosclerotic aneurysm 317).

[Inflammatory aneurysm of the abdominal aorta. Review of the literature of the past 30 years]. / Gli aneurismi infiammatori dell'aorta addominale. Revisione della letteratura dell'ultimo trentennio.

A careful review of the available literature on the clinical and pathologic features of the so-called inflammatory aneurysm of the abdominal aorta is reported. The etiology of this peculiar disease is still obscure and controversial, even if the current trend is to define it as an immunomediate phenomenon consisting on an "exaggerated" inflammatory response to atherosclerosis. Suggestions about the similarity or identity from the pathologic viewpoint, of inflammatory aneurysm, periaortic fibrosis and idiopathic retroperitoneal fibrosis are attractive, but not universally accepted. The surgical treatment aims at the same objectives than for atherosclerotic aneurysms (i.e. prevention of rupture); operative management is however endangered by greater difficulties which hopefully may be reduced in the coming years by the use of corticosteroids and mainly through the wider application of endografting procedures.

Femorofemoral bypass grafts: Factors influencing long-term patency rate and outcome.

BACKGROUND: Crossover femorofemoral bypass graft (CFFBG) was proposed in the early days of modern vascular surgery to treat patients affected with unilateral iliac artery disease who were a high surgical risk. We investigated factors influencing short- and long-term outcomes of CFFBG: METHODS: The study was designed as a retrospective clinical study in a university hospital setting with a base of 228 patients. Of these patients, 154 (67.5%) presented a high surgical risk. The indication for operation was limb-threatening ischemia in 188 (82.5%) patients. All patients underwent CFFBG: The procedure was performed in 150 patients as the primary operation and in 78 patients after previous vascular graft failure or infection, or both. A preoperative percutaneous transluminal angioplasty was performed in 57 patients (25%) to correct donor iliac artery disease. In 127 patients (55.7%), an associated vascular procedure was performed to improve the outflow. Postoperative complications; 5- and 10-year primary, secondary, and limb salvage rates; and factors influencing short- and long-term results were assessed. RESULTS: Thirteen (5.7%) postoperative deaths occurred. Postoperative mortality and morbidity rates were significantly higher in patients aged more than 65 years (7.9% versus 3.5% and 18.6% versus 6.1%, respectively, P <.03). Primary and secondary patency rates at 5 and 10 years were 70.2% and 48.1%, 82.8% and 63.2%, respectively; 5- and 10-year limb salvage and survival rates were 85.5% and 80.1%, 63.3% and 31.0%, respectively. Ten-year primary and secondary patency and limb salvage rates were significantly lower when the procedure was performed after previous vascular graft failures (50.2% versus 26.5%, P <.007; 74.1% versus 44.1%, P <.01; and 84.3% versus 72.5%, P <.03, respectively). Five- and 8-year patency rates of autogenous vein CFFBG (34.3% and 22.8%, respectively, P <.03) were significantly lower than those of expanded polytetrafluoroethylene (71.1% and 59.8%, respectively) and polyester (77.3% and 50.3%, respectively) CFFBG: Moreover, 5- and 10-year primary and secondary patency rates were significantly better when externally supported grafts were used as compared with those without external support (80.1% and 69.9% versus 61.1% and 21.1%, P <.01; 88.8% and 75.9% versus 78.9% and 45.4%, P <.05, respectively). Multivariate analysis showed that the only variable associated with poor primary and secondary patency and limb salvage rates was the operation performed after previous vascular graft failures (P <.04, P <.03 and P<.05, respectively). CONCLUSIONS: CFFBG allows early and long-term results similar to those obtained with reconstructions originating from the aorta when it is performed as a primary operation when an adequate outflow is provided and externally supported prosthetic material is used.

Inflammatory aneurysm of the abdominal aorta. A prospective clinical study.

OBJECTIVE: This study was undertaken to investigate a consecutive series of abdominal aortic aneurysm studied with histology to highlight the etiology, the incidence, the value of preoperative studies and intraoperative findings. EXPERIMENTAL DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Between 1992 and 1994, 102 patients underwent elective surgical repair of an abdominal aortic aneurysm. The patients were prospectively divided as having an inflammatory aneurysm (IA) or an atherosclerotic aneurysm (AA) on the basis of preoperative and intraoperative findings. Further histological evaluation assigned the patients to one of the two groups. RESULTS: The incidence of IA was 15%. Overall, symptoms, CT scan studies, aneurysmal wall thickness, white glistening perianeurysmal fibrosis, bleeding from the aneurysmal wall and adhesion to the duodenum diagnosed 11 (73%) cases of IA. Histology showed that a granulomatous reaction against some components of the atherosclerotic plaques resulting in an auto-allergic response to this component could initiate the inflammatory process thus resulting in a progressive adventitial and peri-adventitial fibrosis with inflammation, lymphadenitis and lymphatic dilatation. CONCLUSIONS: Preoperative and intraoperative findings underestimate the incidence of IA. Aortic resection can prevent the progression of the inflammatory process and the complications usually observed when the exposure to the allergen determines an involvement of the periaortic structures.

Long-term results and outcomes of crossover axilloaxillary bypass grafting: A 24-year experience.

OBJECTIVE: The outcome of crossover axilloaxillary bypass grafting in patients with stenosis or occlusion of the innominate or subclavian arteries was investigated. METHODS: The study was designed as a retrospective clinical study in a university hospital setting with 61 patients as the basis of the study. Fifty-eight patients (95.1%) had at least two risk factors or associated medical illnesses for atherosclerosis, and 35 patients (57.4%) had concomitant carotid artery stenosis that necessitated a staged procedure in 12 patients (19.7%). The patients underwent a total of 63 crossover axilloaxillary bypass grafting procedures. Demographics, risk factors and associated medical illnesses, preoperative symptoms and angiographic data, blood flow inversion in the vertebral artery, concomitant carotid artery disease, graft shape, caliber and material, and intraoperative and postoperative complications were studied to assess the specific influence in determining the outcome. RESULTS: One postoperative death (1.6%), four early graft thromboses (6.2%), and six minor complications (9. 8%) occurred. The overall mortality and morbidity rates were 1.6% and 16.1%, respectively. During the follow-up period (mean, 97.3 +/- 7.9 months), we observed five graft thromboses (8.3%). Primary and secondary patency rates at 5 and 10 years were 86.5% and 82.8% and 88.1% and 84.3%, respectively. Overall, two patients (3.3%) had recurrence of upper limb symptoms and none had recurrence of symptoms in the carotid or vertebrobasilar territory. The 5-year and 10-year symptom-free interval rates were 97.7% and 93.5%, respectively. Nine patients (15%) died of unrelated causes. The 5-year and 10-year survival rates were 93.2% and 67.3%, respectively. Multivariate analysis showed that no specific variables exerted an influence in the short-term and long-term results and the outcome. CONCLUSION: The optimal outcome of axilloaxillary bypass grafting supports its use as the most valuable surgical alternative to transthoracic anatomic reconstructions for innominate lesion, long stenosis of the subclavian artery, and short subclavian artery stenosis associated with ispilateral carotid artery lesions.

Iliorenal bypass for the treatment of type-3 Takayasu's disease. A case report with 10-year follow-up.

The case of a 16-year old female with severe renovascular hypertension resulting from type-3 Takayasu's arteritis is reported. The entire thoracic and abdominal aorta was affected by an active inflammatory process and all its branches were stenotic or occluded. After the early failure of a percutaneous balloon angioplasty of the left renal artery, an iliac to renal artery bypass graft using a reversed autologous saphenous vein was performed through a retroperitoneal tunnel The patient is asymptomatic and the graft is patent at 10-year follow-up.

31Phosphorus magnetic resonance spectroscopy to evaluate medical therapy efficacy in peripheral arterial disease. A pilot study.

BACKGROUND: Human and animal studies have shown that propionyl-L-carnitine, increasing carnitine content, improves the energy metabolism of ischemic skeletal muscle. The aim of the study was to evaluate the accuracy of Doppler continuous wave, Treadmill test and 31Phosphorus magnetic resonance spectroscopy in determining the efficacy of propionyl-L-carnitine in patients with peripheral arterial disease. EXPERIMENTAL DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Eighteen male patients with peripheral arterial disease (category 3) and 8 healthy volunteers form the basis of the study. Patients quit smoking, start physical training (2-3 Km walk per day) and were assigned to medical therapy consisting of propionyl-L-carnitine (8 patients) or placebo (10 patients). Patients were studied with Doppler continuous wave, Treadmill test and 31Phosphorus magnetic resonance spectroscopy at day 0 and at day 90. The following parameters were assessed by the principal component analysis: clinical (absolute claudication, ankle brachial index at rest and at 2, 5 and 10 minutes after completing Treadmill exercises) and biochemical (inorganic phosphorus/phosphocreatine ratio and pH profiles at 20% and 50% of the maximum load, the recovery half time of phosphocreatine, number of exercise steps and slope of linear relationship between muscle power and inorganic phosphorus/phosphocreatine ratio). RESULTS: Final evaluation showed a significant improvement of clinical and biochemical variables (p < 0.05 and p < 0.02 respectively). Breaking down the results on the basis of the two study arms, 31Phosphorus magnetic resonance spectroscopy showed a significant improvement of biochemical variables in the group of patients treated with propionyl-L-carnitine (p < 0.05) and was more sensitive in the evaluation of changes induced by 90-day treatment as compared with the other noninvasive examinations. CONCLUSIONS: 31P-MRS permits the evaluation of muscle metabolic effect induced by PLC after a 90-day-period in patients affected by category 3 of peripheral arterial disease and it is a more sensitive tool in the evaluation of the pharmacological effects of medical therapy.