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Ocular myasthenia is a neuromuscular autoimmune disorder in which the clinical symptoms are restricted to the external ocular muscles with either ptosis or diplopia, or both. The condition may follow a relapsing and remitting course. Conventional therapy consists of anticholinergic drugs, corticosteroids and immunosuppressants. We report a case in which auricular acupuncture was used as an adjunct to pharmacological treatment. The time course of the response suggests that acupuncture appeared to help resolve the current relapse. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSC) include immature monocytic (M-MDSC) and granulocytic (PMN-MDSC) cells that share the ability to suppress adaptive immunity and to hinder the effectiveness of anticancer treatments. Of note, in response to IFNγ, M-MDSCs release the tumor-promoting and immunosuppressive molecule nitric oxide (NO), whereas macrophages largely express antitumor properties. Investigating these opposing activities, we found that tumor-derived prostaglandin E2 (PGE2) induces nuclear accumulation of p50 NF-κB in M-MDSCs, diverting their response to IFNγ toward NO-mediated immunosuppression and reducing TNFα expression. At the genome level, p50 NF-κB promoted binding of STAT1 to regulatory regions of selected IFNγ-dependent genes, including inducible nitric oxide synthase (Nos2). In agreement, ablation of p50 as well as pharmacologic inhibition of either the PGE2 receptor EP2 or NO production reprogrammed M-MDSCs toward a NOS2 low /TNFα high phenotype, restoring the in vivo antitumor activity of IFNγ. Our results indicate that inhibition of the PGE2/p50/NO axis prevents MDSC-suppressive functions and restores the efficacy of anticancer immunotherapy. SIGNIFICANCE: Tumor-derived PGE2-mediated induction of nuclear p50 NF-κB epigenetically reprograms the response of monocytic cells to IFNγ toward an immunosuppressive phenotype, thus retrieving the anticancer properties of IFNγ. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/13/2874/F1.large.jpg., (©2020 American Association for Cancer Research.)

Although tumor-associated macrophages (TAM) display a M2-skewed tumor-promoting phenotype in most cancers, in colorectal cancer, both TAM polarization and its impact remain controversial. We investigated the role of the M2-polarizing p50 NF-κB subunit in orchestrating TAM phenotype, tumor microenvironment composition, and colorectal cancer progression. We first demonstrated, by parallel studies in colitis-associated cancer (CAC) and in genetically driven Apc Min mouse models, that the p50-dependent inhibition of M1-polarized gut inflammation supported colorectal cancer development. In accordance with these studies, p50 -/- mice displayed exacerbated CAC with fewer and smaller tumors, along with enhanced levels of M1/Th1 cytokines/chemokines, including IL12 and CXCL10, whose administration restrained CAC development in vivo The inflammatory profile supporting tumor resistance in colons from p50 -/- tumor bearers correlated inversely with TAM load and positively with both recruitment of NK, NKT, CD8 + T cells and number of apoptotic tumor cells. In agreement, myeloid-specific ablation of p50 promoted tumor resistance in mice, whereas in colorectal cancer patients, a high number of p50 + TAMs at the invasive margin was associated with decreased IL12A and TBX21 expression and worse postsurgical outcome. Our findings point to p50 involvement in colorectal cancer development, through its engagement in the protumor activation of macrophages, and identify a candidate for prognostic and target therapeutic intervention. Cancer Immunol Res; 6(5); 578-93. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Inflammatory cells are an essential component of the tumor microenvironment. Neutrophils have emerged as important players in the orchestration and effector phase of innate and adaptive immunity. The significance of tumor-associated neutrophils (TAN) in colorectal cancer (CRC) has been the subject of conflicting reports and the present study was designed to set up a reliable methodology to assess TAN infiltration in CRC and to evaluate their clinical significance. CD66b and myeloperoxidase (MPO) were assessed as candidate neutrophil markers in CRC using immunohistochemistry. CD66b was found to be a reliable marker to identify TAN in CRC tissues, whereas MPO also identified a subset of CD68(+) macrophages. CRC patients (n = 271) (Stages I-IV) were investigated retrospectively by computer-assisted imaging on whole tumor sections. TAN density dramatically decreases in Stage IV patients as compared to Stage I-III. At Cox analysis, higher TAN density was associated with better prognosis. Importantly, multivariate analysis showed that prognostic significance of TAN can be influenced by clinical stage and 5-fluorouracil(5-FU)-based chemotherapy. On separate analysis of Stage III patients (n = 178), TAN density had a dual clinical significance depending on the use of 5-FU-based chemotherapy. Unexpectedly, higher TAN density was associated with better response to 5-FU-based chemotherapy. Thus, TAN are an important component of the immune cell infiltrate in CRC and assessment of TAN infiltration may help identify patients likely to benefit from 5-FU-based chemotherapy. These results call for a reassessment of the role of neutrophils in cancer using rigorous quantitative methodology., (© 2016 UICC.)

Objectives: To provide a functional and phenotypic characterization of immune cells infiltrating small intestinal mucosa during non-IPEX autoimmune enteropathy (AIE), as to gain insights on the pathogenesis of this clinical condition., Methods: Duodenal biopsies from a patient with AIE at baseline and following drug-induced remission were analyzed by immunohistochemistry, immunofluorescence, and flow cytometry, and results were compared with those obtained from patients with active celiac disease, ileal Crohn's disease and healthy controls. Lamina propria (LP) and intraepithelial (IELs) lymphocytes from AIE and controls were analyzed for mechanisms regulating cytokine production. Foxp3 expression and suppressive functions of LP regulatory T cells (Tregs) were analyzed., Results: The quantitative deficit of Foxp3 expression in Tregs in AIE associates with unrestrained IL-17 production by IELs. Interleukin (IL)-17-producing IELs were rare in the uninflamed duodenum and in the ileum of Crohn's disease patients, and disappeared upon drug-induced AIE remission. IL-17 upregulation in CD4(+)IELs and CD4(+)LP T cells had different requirements for pro-inflammatory cytokines. Moreover, transforming growth factor-β (TGF-β) selectively enhanced IL-17 production by CD8(+)IELs. Intriguingly, although Foxp3(low)Tregs in AIE were poorly suppressive, they could upregulate GARP-LAP/TGF-β surface expression and enhanced IL-17 production selectively by CD8(+)IELs. Finally, phosphorylated Smad2/3 was detectable in duodenal CD8(+) lymphocytes in active AIE in situ, indicating that they received signals from the TGF-β receptor in vivo., Conclusions: AIE is characterized by the appearance of unconventional IL-17-producing IELs, which could be generated locally by pro-inflammatory cytokines and TGF-β. These results suggest that Foxp3(+)Tregs and Treg-derived TGF-β regulate IL-17 production by IELs in the small intestine and in AIE.

Cancer-driven granulo-monocytopoiesis stimulates expansion of tumor promoting myeloid populations, mostly myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). We identified subsets of MDSCs and TAMs based on the expression of retinoic-acid-related orphan receptor (RORC1/RORγ) in human and mouse tumor bearers. RORC1 orchestrates myelopoiesis by suppressing negative (Socs3 and Bcl3) and promoting positive (C/EBPβ) regulators of granulopoiesis, as well as the key transcriptional mediators of myeloid progenitor commitment and differentiation to the monocytic/macrophage lineage (IRF8 and PU.1). RORC1 supported tumor-promoting innate immunity by protecting MDSCs from apoptosis, mediating TAM differentiation and M2 polarization, and limiting tumor infiltration by mature neutrophils. Accordingly, ablation of RORC1 in the hematopoietic compartment prevented cancer-driven myelopoiesis, resulting in inhibition of tumor growth and metastasis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity., (© 2015 Doni et al.)

PTX3 is an essential component of the humoral arm of innate immunity, playing a nonredundant role in resistance against selected microbes and in the regulation of inflammation. PTX3 activates and regulates the Complement cascade by interacting with C1q and with Factor H. PTX3 deficiency was associated with increased susceptibility to mesenchymal and epithelial carcinogenesis. Increased susceptibility of Ptx3(-/-) mice was associated with enhanced macrophage infiltration, cytokine production, angiogenesis, and Trp53 mutations. Correlative evidence, gene-targeted mice, and pharmacological blocking experiments indicated that PTX3 deficiency resulted in amplification of Complement activation, CCL2 production, and tumor-promoting macrophage recruitment. PTX3 expression was epigenetically regulated in selected human tumors (e.g., leiomyosarcomas and colorectal cancer) by methylation of the promoter region and of a putative enhancer. Thus, PTX3, an effector molecule belonging to the humoral arm of innate immunity, acts as an extrinsic oncosuppressor gene in mouse and man by regulating Complement-dependent, macrophage-sustained, tumor-promoting inflammation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disorder caused by the degeneration of motor neurons in the CNS, which results in complete paralysis of skeletal muscles. Recent experimental studies have suggested that the disease could initiate in skeletal muscle, rather than in the motor neurons. To establish the timeframe of motor neuron degeneration in relation to muscle atrophy in motor neuron disease, we have used MRI to monitor changes throughout disease in brain and skeletal muscle of G93A-SOD1 mice, a purported model of ALS. Longitudinal MRI examination of the same animals indicated that muscle volume in the G93A-SOD1 mice was significantly reduced from as early as week 8 of life, 4 weeks prior to clinical onset. Progressive muscle atrophy from week 8 onwards was confirmed by histological analysis. In contrast, brain MRI indicated that neurodegeneration occurs later in G93A-SOD1 mice, with hyperintensity MRI signals detected only at weeks 10-18. Neurodegenerative changes were observed only in the motor nuclei areas of the brainstem; MRI changes indicative of neurodegeneration were not detected in the motor cortex where first motor neurons originate, even at the late disease stage. This longitudinal MRI study establishes unequivocally that, in the experimental murine model of ALS, muscle degeneration occurs before any evidence of neurodegeneration and clinical signs, supporting the postulate that motor neuron disease can initiate from muscle damage and result from retrograde dying-back of the motor neurons., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Impairment of mitochondrial function might contribute to oxidative stress associated with neurodegeneration in amyotrophic lateral sclerosis (ALS). Glutamate levels in tissues of ALS patients are sometimes altered. In neurons, mitochondrial metabolism of exogenous glutamine is mainly responsible for the net synthesis of glutamate, which is a neurotransmitter, but it is also necessary for the synthesis of glutathione, the main endogenous antioxidant. We investigated glutathione synthesis and glutamine/glutamate metabolism in a motor neuronal model of familial ALS. In standard culture conditions (with glutamine) or restricting glutamine or cystine, the level of glutathione was always lower in the cell line expressing the mutant (G93A) human Cu, Zn superoxide dismutase (G93ASOD1) than in the line expressing wild-type SOD1. With glutamine the difference in glutathione was associated with a lower glutamate and impairment of the glutamine/glutamate metabolism as evidenced by lower glutaminase and cytosolic malate dehydrogenase activity. d-β-hydroxybutyrate, as an alternative to glutamine as energy substrate in addition to glucose, reversed the decreases of cytosolic malate dehydrogenase activity and glutamate and glutathione. However, in the G93ASOD1 cell line, in all culture conditions the expression of pyruvate dehydrogenase kinase l protein, which down-regulates pyruvate dehydrogenase activity, was induced, together with an increase in lactate release in the medium. These findings suggest that the glutathione decrease associated with mutant SOD1 expression is due to mitochondrial dysfunction caused by the reduction of the flow of glucose-derived pyruvate through the TCA cycle; it implies altered glutamate metabolism and depends on the different mitochondrial energy substrates., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: The objective of our study was to assess a protocol of study of carotid atherosclerosis coupling vascular wall imaging and luminal imaging in the same examination and to evaluate the accuracy of high-resolution MRI with a neurovascular coil in carotid plaque characterization., Subjects and Methods: Thirty-two consecutive patients with 34 carotid artery stenoses were prospectively enrolled. MRI was performed on a 1.5-T unit. Plaque assessment was performed starting with a diffusion-weighted sequence and followed by a fat-suppressed T1-weighted sequence; after contrast-enhanced MR angiography (CE-MRA), all patients were evaluated with a T1-weighted 3D high-resolution sequence. Carotid plaques were classified as type A, having a large lipid-necrotic core; type B, being a complex fibrotic-calcified plaque with soft content (mixed plaque); or type C, being a fibrotic-calcified plaque (hard). Additional features indicative of vulnerable plaque such as intraplaque hemorrhage (IPH), ulceration, and severe stenosis were registered. MR findings were compared with surgical specimens., Results: MRI correctly identified 11 of 13 type A, eight of 11 type B, and eight of 10 type C plaques (sensitivity, 84.6%, 72.7%, and 80%, respectively). In the identification of lipid-necrotic core plaque, MRI showed a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 84.6%, 100%, 100%, and 91.3%, respectively (κ = 0.87). For reordering all plaques in two groups (i.e., soft vs nonsoft) in the identification of soft plaques, MRI had a sensitivity, specificity, PPV, and NPV of 83.3%, 80%, 90.9%, and 66.7%, respectively (κ = 0.59). IPH, ulcers, and severe stenosis were detected in eight of eight, 11 of 13, and 25 of 25 cases, respectively., Conclusion: In patients with carotid atherosclerosis, ongoing CE-MRA with a neurovascular coil for the simultaneous detection of unstable plaques is feasible. Our MR protocol accurately identifies the major features of vulnerable plaque.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease, and protein aggregation has been proposed as a possible pathogenetic mechanism. However, the aggregate protein constituents are poorly characterized so knowledge on the role of aggregation in pathogenesis is limited., Methodology/principal Findings: We carried out a proteomic analysis of the protein composition of the insoluble fraction, as a model of protein aggregates, from familial ALS (fALS) mouse model at different disease stages. We identified several proteins enriched in the detergent-insoluble fraction already at a preclinical stage, including intermediate filaments, chaperones and mitochondrial proteins. Aconitase, HSC70 and cyclophilin A were also significantly enriched in the insoluble fraction of spinal cords of ALS patients. Moreover, we found that the majority of proteins in mice and HSP90 in patients were tyrosine-nitrated. We therefore investigated the role of nitrative stress in aggregate formation in fALS-like murine motor neuron-neuroblastoma (NSC-34) cell lines. By inhibiting nitric oxide synthesis the amount of insoluble proteins, particularly aconitase, HSC70, cyclophilin A and SOD1 can be substantially reduced., Conclusion/significance: Analysis of the insoluble fractions from cellular/mouse models and human tissues revealed novel aggregation-prone proteins and suggests that nitrative stress contribute to protein aggregate formation in ALS.

Motor neuron degeneration in amyotrophic lateral sclerosis involves oxidative damage. Glutathione (GSH) is critical as an antioxidant and a redox modulator. We used a motor neuronal cell line (NSC-34) to investigate whether wild-type and familial amyotrophic lateral sclerosis-linked G93A mutant Cu,Zn superoxide dismutase (wt/G93ASOD1) modified the GSH pool and glutamate cysteine ligase (GCL), the rate-limiting enzyme for GSH synthesis. We studied the effect of various G93ASOD1 levels and exposure times. Mutant Cu,Zn superoxide dismutase induced an adaptive process involving the upregulation of GSH synthesis, even at very low expression levels. However, cells with a high level of G93ASOD1 cultured for 10 weeks showed GSH depletion and a decrease in expression of the modulatory subunit of GCL. These cells also had lower levels of GSH and GCL activity was not induced after treatment with the pro-oxidant tert-butylhydroquinone. Cells with a low level of G93ASOD1 maintained higher GSH levels and GCL activity, showing that the exposure time and the level of the mutant protein modulate GSH synthesis. We conclude that failure of the regulation of the GSH pathway caused by G93ASOD1 may contribute to motor neuron vulnerability and we identify this pathway as a target for therapeutic intervention.

Aim: The aim of the study was the evaluation of postoperative short term analgesia-based sedation provided by a continuous i.v. morphine vs morphine+remifentanil infusion in the ICU., Methods: A prospective, randomized, controlled study was carried out., Inclusion Criteria: patients aged > 18 years undergoing major surgery (abdominal, vascular, thoracic). A total of 100 patients undergoing balanced anaesthesia, were enrolled; at the end of surgery an i.v. loading morphine dose (0.1 mg/kg) was administered and a continuous ground i.v. infusion (0.24 microg/kg/min) was started. When the patient was admitted to the ICU, a second i.v. continuous infusion was started and patients were allocated into 2 groups with regard to the second opioid: MM = morphine + morphine, MR = morphine + remifentanil. The second continuous infusion (boluses allowed) was titrated to obtain a numerical rate score (NRS) < 3 and Ramsay Scale =or>2. If Ramsay =or< 2 rescue sedation was administered (diazepam)., Results: The groups were homogeneous with regard to gender, age, weight, duration of surgery, intraoperative opioids, SAPS II. The second infusion rate in the first 24 postoperative hours was 0.73+/-0.55 microg/kg/min morphine in MM and 0.06+/-0.05 microg/kg/min remifentanil in RM. Hemodynamic parameters and SpO(2) were similar. Hypnotic consumption and NRS were significantly lower in RM, while Ramsay Scale was higher. Postextubation respiratory rate and minute volume were lower in group MM, while PaCO(2), postoperative nausea and vomiting (PONV) incidence and frequency of diazepam administration were higher. In both groups more than 70% of the patients were very satisfied., Conclusion: The combination of morphine + remifentanil provided better analgesia and sedation than morphine alone, with a lower incidence of side effects and a similar hemodynamic profile and patient satisfaction. The adherence to a clear analgesia based sedation protocol probably represents the most important issue carrying out analgosedation; however, the continuous infusion of a short acting drug, although more expensive, allows better titration and adjustment of the desired level of analgesia and sedation, avoiding the risk of undersedation as well as oversedation with a potential reduction of otherwise unnecessary ICU stays and, consequently, a decrease in comprehensive costs.

Objectives.  Vertebral fractures are the most common consequences of severe osteoporosis. The chronic pain from collapse of osteoporotic vertebrae affects quality of life (QoL) and autonomy of patients. The management of pain with oral or transdermal opiates can cause severe side-effects. Continuous intrathecal administration of morphine through an implantable pump might represent an alternative therapy to conventional oral or transdermal administration of opioids and has some advantages and disadvantages for pain relief and improvement in QoL when compared to conventional opioid delivery. It is our objective to report our experience using intrathecal delivery of analgesics in a population of patients with refractory pain due to vertebral fractures. Materials and Methods.  In 24 patients, refractory to conventional delivery of opioids, we used intrathecal analgesic therapy. To test for efficacy and improvement in QoL, we administered the visual analog scale (VAS) for pain and the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). Before patients were selected for pump implantation, an intraspinal drug delivery trial was performed to monitor side-effects and responses to intrathecal therapy. Results.  Significant pain relief was obtained in all implanted patients. Using the QUALEFFO, we observed significant improvement of all variables such as QDL (quality of daily life), DW (domestic work), ambulation, and PHS (perception of health status), before and after one year after pump implantation. With intrathecal morphine infusion, none of the 24 patients required additional systemic analgesic medication. The mean morphine dose during the spinal trial was 11.28 mg/day, 7.92 mg/day at pump implantation, and 16.32 mg/day at one-year follow-up. Conclusions.  Our results show that intrathecal administration of morphine efficiently relieves the symptoms of pain and improves QoL. Continuous intrathecal administration of morphine appears to be an alternative therapy to conventional analgesic drug delivery and has advantages in those patients who have severe side-effects with systemic administration of analgesics.

Mitochondrial damage induced by superoxide dismutase (SOD1) mutants has been proposed to have a causative role in the selective degeneration of motoneurons in amyotrophic lateral sclerosis (ALS). In order to investigate the basis of the tissue specificity of mutant SOD1 we compared the effect of the continuous expression of wild-type or mutant (G93A) human SOD1 on mitochondrial morphology in the NSC-34 motoneuronal-like, the N18TG2 neuroblastoma and the non-neuronal Madin-Darby Canine Kidney (MDCK) cell lines. Morphological alterations of mitochondria were observed in NSC-34 expressing the G93A mutant (NSC-G93A) but not the wild-type SOD1, whereas a ten-fold greater level of total expression of the mutant had no effect on mitochondria of non-motoneuronal cell lines. Fragmented network, swelling and cristae remodelling but not vacuolization of mitochondria or other intracellular organelles were observed only in NSC-G93A cells. The mitochondrial alterations were not explained by a preferential localization of the mutant within NSC-G93A mitochondria, as a higher amount of the mutant SOD1 was found in mitochondria of MDCK-G93A cells. Our results suggest that mitochondrial vulnerability of motoneurons to G93ASOD1 is recapitulated in NSC-34 cells, and that peculiar features in network dynamics may account for the selective alterations of motoneuronal mitochondria.

Aim: The purpose of this prospective, randomized, controlled study was the comparison of maximal sterile barrier (consisting of mask, cap, sterile gloves, gown, large drape) vs control precautions (mask, cap, sterile gloves, small drape) and of transparent polyurethan film vs gauze dressing for use on central venous (CVC) nontunneled catheters, inserted via the jugular vein. Skin colonization at the insertion site (defined by quantitative skin cultures performed at the time of insertion and in days 2 and 5) was used as a primary endpoint. Catheter tip colonization was also assessed through qualitative culture and CVC related sepsis was defined by the isolation of the same organism from the catheter tip and the blood, with clinical sepsis of no other apparent source., Methods: Eighty-two consecutive patients were enrolled, admitted to a mixed medical-surgical ICU, aged 72+/-12 years, 58% male, SAPS II 42+/-13. One-hundred and seven CVCs were studied (presenting 750 catheter in situ days); CVCs were in place for a mean period of 6.9+/-4.7 days and 5 episodes of central catheter-related bloodstream infection were detected (6.6 per 1000 catheter days)., Results: A multiple logistic regression detected an increased risk of skin colonization in male gender (OR=2.5) and control precautions (OR=3.4) and no difference with regard to age, dressing and diagnostic group., Conclusions: Maximal sterile barrier proved to be an effective and recommended practice. However surveillance skin cultures revealed the common and changing nature of colonization of skin at the insertion site.

Aim: To evaluate the feasibility and efficacy of subintimal infrapopliteal angioplasty (SIA) as a method for recanalization of occluded tibial arteries in the treatment of critical limb ischaemia (CLI)., Materials and Methods: Between January 2002 and September 2003, 20 patients with CLI were submitted to SIA; of these, 16 had diabetes mellitus. All patients had foot ulceration or gangrene and ten had rest pain. All patients were treated with SIA of one or more vessels of the popliteal district. Overall, thirty-four arteries of the infrapopliteal district underwent revascularization; in 9 cases, SIA of superficial femoral artery occlusions was associated. Technical success was evaluated on angiography at the end of the procedure: revascularization of at least one of the 3 leg vessels with re-establishment of arterial flow to the foot was regarded as a technical success. Pain relief (when pain was present) and healing of foot ulceration, without above-the-ankle major amputation (limb salvage), were defined as clinically successful. During the follow-up (mean: 9 months; range: 6-21 months) all patients were checked 6 months after the procedure by clinical examination and colour-Doppler ultrasound., Results: The technical success rate of SIA in the revascularization of the infrapopliteal vessels was 85%. In the 17 technically successful cases, pain had entirely resolved in 9/10 cases and trophic lesions of the foot healed in 14/17 cases. In this group, 9 patients underwent minor amputation; 2 underwent major above-the-ankle amputation; one underwent to surgery 20 days after the SIA and required a femoro-tibial by-pass. In the 3 cases of technical failure (15%), revascularization of the entire occluded tract could not be achieved. Of these, one patient subsequently underwent major amputation. Nine months after SIA, the cumulative limb salvage rate was 85% (17/20 clinically successful cases) and the survival rate was 90%. Colour-Doppler US at 6 months showed 70% primary patency. No major complication occurred during the procedure. Five minor complications in four patients were managed endovascularly or healed spontaneously., Conclusions: SIA is a feasible and effective technique for foot revascularization in patients with CLI. Long occlusions or diffusely calcified arteries are suitable indications. Technical failure does not preclude conventional surgery. In patients treated with SIA, the risk of major amputation is low and mortality rate is nil. Minor complications can be managed using endovascular techniques.