Vitamin K in CKD Bone Disorders.

Vitamin K is principally known because it is involved in blood coagulation. Furthermore, epidemiological studies showed that its deficit was associated with increased fragility fractures, vascular calcification and mortality. There are two main types of vitamin K vitamers: Phylloquinone (or PK) and Menaquinones (MKn). Vitamin K acts both as coenzyme of y-glutamyl carboxylase (GGCX) transforming undercarboxylated in carboxylated vitamin K-dependent proteins (e.g., Osteocalcin and Matrix Gla Protein) and as a ligand of the nuclear steroid and xenobiotic receptor (SXR) (in murine species Pregnane X Receptor: PXR), expressed in osteoblasts. It has been highlighted that the uremic state is a condition of greater vitamin K deficiency than the general population with resulting higher prevalence of bone fractures, vascular calcifications and mortality. The purpose of this literature review is to evaluate the protective role of Vitamin K in bone health in CKD patients.

Influence of cognitive stance and physical perspective on subjective and autonomic reactivity to observed pain and pleasure: An immersive virtual reality study.

Observing others' pain may induce a reaction called personal distress that may be influenced by top-down (imagine self or other in pain, i.e., self- vs other-oriented stance) and bottom-up (physical perspective of those who suffer, i.e., first vs third person perspective- 1PP vs 3PP) processes. The different contributions of these processes have not been teased apart. By capitalizing on the power of Immersive Virtual Reality, we explored how behavioural (subjective ratings) and physiological reactivity (skin conductance reactivity, SCR) to pain and pleasure delivered to an avatar was influenced by Cognitive stance and Physical perspective. Taking an Other-Oriented stance leads to attributing higher congruent valence (i.e. pain rated as unpleasant and pleasure as pleasant) and intensity to the stimuli and induces reduced SCR. Ownership over the virtual limb was maximal in 1PP where physiological reactivity to the stimuli was comparable. Our results highlight different components underpinning reactivity to pain and pleasure.

Short-term swimming exercise attenuates the sensitization of dorsal horn neurons in rats with NGF-induced low back pain.

BACKGROUND: Physical exercise has been shown to be an effective therapy for non-specific low back pain. The study investigated if swimming exercise is a means to reduce the spinal sensitization in an animal model of non-specific low back pain. METHODS: In deeply anesthetized rats, dorsal horn neurons were recorded in spinal segment L2. To induce sensitization of dorsal horn neurons, two injections of nerve growth factor were made into the lumbar multifidus muscle at an interval of 5 days. Swimming exercise for 30 min was performed on the 5 days between both NGF injections. A control group received the NGF injections without exercise treatment. RESULTS: Swimming exercise caused a significant decrease in the NGF-induced hyperexcitability of dorsal horn neurons. Compared to control, the proportion of neurons with input from deep somatic tissues and of convergent neurons with input from at least two types of different tissues decreased significantly (50% vs. 25% and 37% vs. 15%; both p < 0.05). Swimming exercise also reduced the NGF-induced increase in neuronal resting activity. Both the proportion of active neurons and the mean discharge frequency of all neurons decreased significantly (60%, 76.3 ± 23.1 imp/min; vs. 25%, 51.7 ± 35.1 imp/min; both p < 0.01). CONCLUSIONS: In our animal model of low back pain, short-term swimming exercise effectively reduced the latent sensitization of spinal dorsal horn neurons. Swimming exercise decreased the hyperexcitability of the neurons to low back input and lowered the resting activity of sensitized neurons. SIGNIFICANCE: Physical exercise is a common treatment for low back pain. The possible mechanisms underlying the effects of exercise are probably multifold. This work shows that swimming exercise prevents sensitization of dorsal horn neurons, which may be one mechanism for the positive effects of exercise.

A comparison of gamma-glutamyl transferase and alkaline phosphatase as prognostic markers in patients with coronary heart disease.

BACKGROUND AND AIMS: Whether gamma-glutamyl transferase (GGT) or alkaline phosphatase (ALP) is a better prognostic marker in patients with coronary heart disease (CHD) remains unknown. The aim of this study was to compare the prognostic value of GGT and ALP in patients with CHD. METHODS AND RESULTS: This study included 3768 patients with CHD. The main study outcome was 3-year all-cause mortality. The median values of GGT and ALP were 36.2 U/L and 69.3 U/L. Patients were divided into subgroups according to GGT or ALP activity > or ≤median. Overall, there were 304 deaths: 195 deaths occurred in patients with GGT >median (n = 1882) and 109 deaths occurred in patients with GGT ≤median (n = 1886); Kaplan-Meier [KM] estimates of all-cause mortality were 11.9% and 6.4% (unadjusted hazard ratio [HR] = 1.85, 95% confidence interval [CI], 1.46 to 2.34]; P < 0.001). According to ALP activity, 186 deaths occurred in patients with ALP >median (n = 1883) and 118 deaths occurred in patients with ALP ≤median (n = 1885); KM estimates of all-cause mortality were 11.4% and 7.1% (unadjusted HR = 1.64 [1.30-2.06]; P < 0.001). After adjustment, GGT (adjusted HR = 1.32 [1.11-1.58]; P = 0.002) but not ALP (adjusted HR = 1.20 [1.00-1.43]; P = 0.051, with both HR calculated per 1 unit increment in logarithmic GGT or ALP scale) remained significantly associated with the risk for mortality. The C statistic of the mortality model with GGT was greater than the C statistic of the model with ALP (0.831 [0.802-0.859] vs. 0.826 [0.793-0.855]; P < 0.001). CONCLUSIONS: In patients with CHD, GGT was a stronger correlate of all-cause mortality than ALP.

Seeing pain and pleasure on self and others: behavioral and psychophysiological reactivity in immersive virtual reality.

Studies have explored behavioral and neural responses to the observation of pain in others. However, much less is known about how taking a physical perspective influences reactivity to the observation of others' pain and pleasure. To explore this issue we devised a novel paradigm in which 24 healthy participants immersed in a virtual reality scenario observed a virtual: needle penetrating (pain), caress (pleasure), or ball touching (neutral) the hand of an avatar seen from a first (1PP)- or a third (3PP)-person perspective. Subjective ratings and physiological responses [skin conductance responses (SCR) and heart rate (HR)] were collected in each trial. All participants reported strong feelings of ownership of the virtual hand only in 1PP. Subjective measures also showed that pain and pleasure were experienced as more salient than neutral. SCR analysis demonstrated higher reactivity in 1PP than in 3PP. Importantly, vicarious pain induced stronger responses with respect to the other conditions in both perspectives. HR analysis revealed equally lower activity during pain and pleasure with respect to neutral. SCR may reflect egocentric perspective, and HR may merely index general arousal. The results suggest that behavioral and physiological indexes of reactivity to seeing others' pain and pleasure were qualitatively similar in 1PP and 3PP. Our paradigm indicates that virtual reality can be used to study vicarious sensation of pain and pleasure without actually delivering any stimulus to participants' real body and to explore behavioral and physiological reactivity when they observe pain and pleasure from ego- and allocentric perspectives.

Nephrolithiasis, bone mineral density, osteoporosis, and fractures: a systematic review and comparative meta-analysis.

Our meta-analysis demonstrates that people with nephrolithiasis have decreased bone mineral density, an increased odds of osteoporosis, and potentially an elevated risk of fractures. INTRODUCTION: People with nephrolithiasis might be at risk of reduced bone mineral density (BMD) and fractures, but the data is equivocal. We conducted a meta-analysis to investigate if patients with nephrolithiasis have worse bone health outcomes (BMD), osteoporosis, and fractures versus healthy controls (HCs). METHODS: Two investigators searched major databases for articles reporting BMD (expressed as g/cm2 or a T- or Z-score), osteoporosis or fractures in a sample of people with nephrolithiasis, and HCs. Standardized mean differences (SMDs), 95 % confidence intervals (CIs) were calculated for BMD parameters; in addition odds (ORs) for case-control and adjusted hazard ratios (HRs) in longitudinal studies for categorical variables were calculated. RESULTS: From 1816 initial hits, 28 studies were included. A meta-analysis of case-control studies including 1595 patients with nephrolithiasis (mean age 41.1 years) versus 3402 HCs (mean age 40.2 years) was conducted. Patients with nephrolithiasis showed significant lower T-scores values for the spine (seven studies; SMD = -0.69; 95 % CI = -0.86 to -0.52; I 2 = 0 %), total hip (seven studies; SMD = -0.82; 95 % CI = -1.11 to -0.52; I 2 = 72 %), and femoral neck (six studies; SMD = -0.67; 95 % CI = --1.00 to -0.34; I 2 = 69 %). A meta-analysis of the case-controlled studies suggests that people with nephrolithiasis are at increased risk of fractures (OR = 1.15, 95 % CI = 1.12-1.17, p < 0.0001, studies = 4), while the risk of fractures in two longitudinal studies demonstrated trend level significance (HR = 1.31, 95 % CI = 0.95-1.62). People with nephrolithiasis were four times more likely to have osteoporosis than HCs (OR = 4.12, p < 0.0001). CONCLUSIONS: Nephrolithiasis is associated with lower BMD, an increased risk of osteoporosis, and possibly, fractures. Future screening/preventative interventions targeting bone health might be indicated.

Muscle hyperalgesia induced by peripheral P2X3 receptors is modulated by inflammatory mediators.

ATP, via activation of P2X3 receptors, has been highlighted as a key target in inflammatory hyperalgesia. Therefore, the aim of this study was to confirm whether the activation of P2X3 receptors in the gastrocnemius muscle of rats induces mechanical muscle hyperalgesia and, if so, to analyze the involvement of the classical inflammatory mediators (bradykinin, prostaglandins, sympathetic amines, pro-inflammatory cytokines and neutrophil migration) in this response. Intramuscular administration of the non-selective P2X3 receptor agonist α,ß-meATP in the gastrocnemius muscle of rats induced mechanical muscle hyperalgesia, which, in turn, was prevented by the selective P2X3 and P2X2/3 receptors antagonist A-317491, the selective bradykinin B1-receptor antagonist Des-Arg9-[Leu8]-BK (DALBK), the cyclooxygenase inhibitor indomethacin, the ß1- or ß2-adrenoceptor antagonist atenolol and ICI 118,551, respectively. Also, the nonspecific selectin inhibitor fucoidan. α,ß-meATP induced increases in the local concentration of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß), which were reduced by bradykinin antagonist. Finally, α,ß-meATP also induced neutrophil migration. Together, these findings suggest that α,ß-meATP induced mechanical hyperalgesia in the gastrocnemius muscle of rats via activation of peripheral P2X3 receptors, which involves bradykinin, prostaglandins, sympathetic amines, pro-inflammatory cytokines release and neutrophil migration. It is also indicated that bradykinin is the key modulator of the mechanical muscle hyperalgesia induced by P2X3 receptors. Therefore, we suggest that P2X3 receptors are important targets to control muscle inflammatory pain.

Peripheral P2X7 receptor-induced mechanical hyperalgesia is mediated by bradykinin.

P2X7 receptors play an important role in inflammatory hyperalgesia, but the mechanisms involved in their hyperalgesic role are not completely understood. In this study, we hypothesized that P2X7 receptor activation induces mechanical hyperalgesia via the inflammatory mediators bradykinin, sympathomimetic amines, prostaglandin E2 (PGE2), and pro-inflammatory cytokines and via neutrophil migration in rats. We found that 2'(3')-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate triethylammonium salt (BzATP), the most potent P2X7 receptor agonist available, induced a dose-dependent mechanical hyperalgesia that was blocked by the P2X7 receptor-selective antagonist A-438079 but unaffected by the P2X1,3,2/3 receptor antagonist TNP-ATP. These findings confirm that, although BzATP also acts at both P2X1 and P2X3 receptors, BzATP-induced hyperalgesia was mediated only by P2X7 receptor activation. Co-administration of selective antagonists of bradykinin B1 (Des-Arg(8)-Leu(9)-BK (DALBK)) or B2 receptors (bradyzide), ß1 (atenolol) or ß2 adrenoceptors (ICI 118,551), or local pre-treatment with the cyclooxygenase inhibitor indomethacin or the nonspecific selectin inhibitor fucoidan each significantly reduced BzATP-induced mechanical hyperalgesia in the rat hind paw. BzATP also induced the release of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6 and cytokine-induced neutrophil chemoattractant-1 (CINC-1), an effect that was significantly reduced by A-438079. Co-administration of DALBK or bradyzide with BzATP significantly reduced BzATP-induced IL-1ß and CINC-1 release. These results indicate that peripheral P2X7 receptor activation induces mechanical hyperalgesia via inflammatory mediators, especially bradykinin, which may contribute to pro-inflammatory cytokine release. These pro-inflammatory cytokines in turn may mediate the contributions of PGE2, sympathomimetic amines and neutrophil migration to the mechanical hyperalgesia induced by local P2X7 receptor activation.

Safety and efficacy of the Yukon Choice Flex sirolimus-eluting coronary stent in an all-comers population cohort.

AIMS: The use of biodegradable-polymer drug-eluting stents has been shown to provide favorable results when compared with durable polymer drug-eluting stents and long-term follow up data have recently shown significant reductions in terms of very late stent thrombosis. Aim of the present study was to assess the safety and efficacy profile of a novel biodegradable polymer DES, the Yukon Choice Flex sirolimus-eluting stent. METHODS: We report here the one-year clinical outcomes associated with the use of the Yukon Choice Flex sirolimus-eluting stent in an all-comers patient population. The present stent represents a further refinement of the stent platform tested in the ISAR TEST 3 and 4 randomized clinical trials. A total of 778 consecutive patients undergoing implantation of this stent were enrolled in the present observational study and prospectively followed for one year. RESULTS: The use of the Yukon Choice Flex stent in a patient population with complex coronary lesion morphology was associated with optimal immediate angiographic results. At one year follow up the rates of death, myocardial infarction, definite stent thrombosis and ischemia-driven target lesion revascularization were respectively 2.4%, 1.9%, 0.3% and 11.3%. CONCLUSIONS: The use of the sirolimus-eluting biodegradable polymer Yukon Choice Flex stent in an all-comers population of patients with complex coronary artery disease is associated with a favorable safety and efficacy profile up to one year follow up.

A gender-specific analysis of association between hyperuricaemia and cardiovascular events in patients with coronary artery disease.

BACKGROUND AND AIMS: Gender-related differences in the association between hyperuricaemia and cardiovascular events remain poorly understood. The objective of this study was to assess gender-related differences in the association between hyperuricaemia and cardiovascular events in patients with coronary artery disease (CAD). METHODS AND RESULTS: This study included 13,273 patients with CAD. Hyperuricaemia was defined as a plasma uric acid >7.0mgdl(-1) in men and >5.7mgdl(-1) in women. The primary outcome was 1-year all-cause mortality. Hyperuricaemia was found in 3745 men (36.5%) and 1562 women (50.3%); odds ratio (OR)=1.76, 95% confidence interval (CI) 1.62-1.91; P<0.001. Women with hyperuricaemia were older, had higher proportions of patients with diabetes and arterial hypertension and had reduced renal function and higher C-reactive protein levels compared with men with hyperuricaemia. One-year all-cause mortality was 9.3% (n=143) in women with hyperuricaemia versus 6.9% (n = 252) in men with hyperuricaemia (P=0.002). After adjustment in multivariable Cox proportional hazards model, uric acid predicted 1-year mortality with an adjusted hazard ratio (HR)=1.17, 95% CI (1.03-1.31), P=0.012 in men and HR=1.25, 95% CI (1.06-1.48), P=0.007 in women, for each standard deviation increase in the natural logarithm. Uric acid predicted 1-year mortality with an area under the receiver-operating characteristic curve=0.625, 95% CI (0.594-0.656) in men and 0.676, 95% CI (0.635-0.717) in women (P=0.044, for women versus men). CONCLUSION: Hyperuricaemia predicts an increased risk of 1-year mortality in both genders with a stronger association in women. Differences in cardiovascular risk profile may explain the stronger association between hyperuricaemia and cardiovascular events in women.

Neuronal P2X3 receptor activation is essential to the hyperalgesia induced by prostaglandins and sympathomimetic amines released during inflammation.

We have demonstrated that the activation of P2X3 receptor on peripheral afferent neurons is critical to development of inflammatory hyperalgesia in peripheral tissue, although pharmacological administration of prostaglandin E(2) or sympathomimetic amines is enough to sensitize primary afferent neurons by acting directly in neuronal receptors. Therefore, to clarify this ambiguity this study verifies whether P2X3 receptor activation on primary afferent neurons enables the sensitization induced by prostaglandin E(2) or sympathomimetic amine. Initially, this study confirmed that co-administration of A317491 (60 µg/paw), a selective P2X3 receptor antagonist, or pre-treatment with dexamethasone (1 mg/mL/kg) prevents the mechanical hyperalgesia induced by carrageenan (300 µg/paw) in the rat's hind paw. Sub-threshold doses of PGE(2) (4 ng/paw) or dopamine (0.4 µg/paw), that do not induce hyperalgesia by themselves, when injected just following αßmeATP or carrageenan in rats treated with dexamethasone induced hyperalgesia, which is prevented by A317491 or treatment with periganglionar (DRG-L5) injections of ODN-antisense, against P2X3 receptor. Furthermore, because PKCɛ translocation induces an increase of neuronal susceptibility to inflammatory mediators, this study demonstrates that αßmeATP in peripheral tissue increases the expression of PKCɛ in cell membranes of DRG-L5, and in contrast, the administration of PKCɛ translocation inhibitor (1 µg/paw) in peripheral tissue 45 min before αßmeATP, prevented the hyperalgesia induced by sub-threshold dose of PGE(2) (4 ng/paw). In conclusion, this study suggests that neuronal P2X3 receptor activation and the consequent PKCɛ translocation increase the susceptibility of nociceptor to inflammatory mediators allowing the development of inflammatory hyperalgesia.

Vitamin K, bone fractures, and vascular calcifications in chronic kidney disease: an important but poorly studied relationship.

Vitamin K denotes a group of lipophilic vitamins determining post-translational modification of proteins. There are 2 main forms of vitamin K: vitamin K1 (phylloquinone, found in vegetables); vitamin K2 (menaquinone, produced by bacteria in the intestine and in fermented foods). Vitamin K stores are limited in humans, but it can be recycled. Vitamin K1 is principally transported to the liver, regulating the production of coagulation factors. Vitamin K2, instead, is also transported to extra-hepatic tissues, such as bone and arteries, regulating the activity of matrix Gla-protein (MGP) and osteocalcin [bone Gla-protein (BGP)]. In patients with chronic kidney disease (CKD), cardiovascular mortality is the first cause of death. Some pathogenetic mechanisms of vascular calcification (such as hyperparathyroidism, hyperphosphatemia, hypercalcemia, role of vitamin D) have been widely investigated, but the potential role of vitamin K is still uncertain. Vitamin K could play a key role, as it transforms glutamic acid residues into γ-carboxyglutamic acid, through a carboxylation process, makings both MGP (cMGP) and BGP (cBGP) biologically active. cMGP inhibits vascular calcifications (VC), while cBGP has an important role for a proper mineralization process. Uncarboxylated MGP and BGP (ucMGP and ucBGP) concentrations are indirect markers of vitamin K2 deficiency. The purpose of this review is to analyze the current literature to understand the relationship between vitamin K2 status, fragility fractures and VC in CKD patients. This analysis could be of help in planning investigations of Vitamin K status and its possible supplementation in CKD patients to avert fragility fractures and VC.

Vertebral fractures in dialysis: Endocrinological disruption of the bone-kidney axis.

The occurrence of metabolic bone disease in patients with renal dysfunction is due to the key role played by the kidney in regulating calcium-phosphate metabolism. The incidence of hip fractures in end-stage renal disease is 3- to 4-fold higher than the general population, while poor data about vertebral fractures show similar prevalence. Bone health has been mainly evaluated in the general population through bone mass density (BMD) measurements, while in Chronic Kidney Disease (CKD) patients, bone turnover (low or high turnover) has been considered the most relevant parameter. Indeed, in CKD patients, the association between BMD and fractures is unclear, and even studies on established risk factors (body mass index, PTH, and vitamin D) for fractures have contrasting outcomes. Recently, an important association has been found between bone disorders and vascular calcifications in CKD patients that has changed the denomination of renal osteodystrophy in CKD mineral and bone disorder. In this article, a poorly investigated subject, vertebral fractures in CKD patients, is addressed, as it is underestimated despite its remarkable clinical relevance.

Cardiac computed tomography in the evaluation of left anterior descending coronary artery with vein patch reconstruction.

PURPOSE: This study evaluated the morphological and functional results of surgical reconstruction of the left anterior descending (LAD) coronary artery with an autologous vein patch, associated with left internal mammary artery (LIMA) grafting onto the patch. MATERIALS AND METHODS: Cardiac computed tomography (CT) images were assessed in terms of functional and morphological parameters. Function was evaluated by assessing patency at 36 months of the reconstructed LAD (based on the attenuation of the native vessel distal to the anastomosis). Morphology was evaluated by studying vein-patch diameters, profiles and margins, shape and structure to categorise the patches into three groups (A, B, C). Within 1 month of CT, all patients underwent functional testing (bicycle ergometry). RESULTS: CT imaging correctly depicted the LAD graft, revealing it to be fully patent in all cases. On the basis of our morphological classification, 21 patients were classed as group A, two as group B and two as group C. At bicycle ergometry, 23 patients were negative and two were positive. Group C patients had the worst functional results. CONCLUSIONS: Cardiac CT allowed adequate evaluation of the LAD graft patency and morphology, and in consideration of its noninvasive nature, it may become the imaging tool of choice for evaluating extended LAD reconstruction.

Cleaved high-molecular-weight kininogen and its domain 5 inhibit migration and invasion of human prostate cancer cells through the epidermal growth factor receptor pathway.

Upregulation and activation of epidermal growth factor receptor and/or urokinase-type plasminogen activator receptor in a variety of cancers have been shown to be associated with poor prognosis. High-molecular-weight kininogen can be hydrolysed by plasma kallikrein to bradykinin and cleaved high-molecular-weight kininogen (HKa). HKa and its domain 5 (D5) both have been shown to have potent anti-angiogenic activity. We now show that HKa blocks human prostate cancer cell (DU145) migration by 76.0+/-2.4% at 300 nM and invasion by 78.0+/-12.9% at 11.1 nM. D5 inhibits tumor migration and invasion in a concentration-dependent manner. Stimulation by basic fibroblast growth factor (bFGF) or vascular endothelial growth factor results in clustering of urokinase-type plasminogen activator receptor (uPAR) and epidermal growth factor receptor (EGFR) on the surface of DU145 cells. The co-localization of uPAR and EGFR is prevented by HKa. Immunoprecipitation suggests that uPAR, EGFR and alpha5beta1 integrin formed a ternary complex. Immunoblotting shows that HKa significantly decreases the bFGF-transactivated phosphorylation of EGFR at Tyr 1173 between 30 min and 4 h. The phosphorylation of extracellular signal-regulated kinase (ERK) and AKT, which are downstream effectors of EGFR, is also inhibited by HKa. These novel data indicate that HKa and D5 inhibit migration and invasion of human prostate cancer cells through an EGFR/uPAR pathway, suggesting the therapeutic potential of HKa and D5 to decrease metastasis of human prostate cancer.

Clinical results of below-the knee intervention using pedal-plantar loop technique for the revascularization of foot arteries.

AIM: Recent registries and randomized trials support the role of percutaneous revascularization in patients with critical limb ischemia (CLI) due to below-the-knee (BTK) atherosclerotic disease, as percutaneous transluminal angioplasty (PTA) for BTK disease has shown to be feasible and safe in this setting. Nonetheless, succes rates remain suboptimal with current techniques. The authors aimed to appraise clinical results following PTA of foot vessels exploiting a novel technique, based on the recanalization of both pedal and plantar arteries and their anatomical anastomosis in order to restore direct arterial in-flow from both anterior and posterior tibial vessels, defined as the pedal-plantar loop technique. METHODS: Baseline, procedural and mid-term outcome data of all consecutive patients with CLI due to BTK disease in which PTA was attempted using the pedal-plantar loop technique were prospectively collected between January 2007 and September 2008. The primary end-point was acute success (i.e. the composite of technical, angiographic and procedural success). Secondary end-points included limb salvage rate, major (above the ankle) and minor (below the ankle) amputation, change in Rutherford class and transcutaneous oxygen tension, reocclusion/restenosis, rehospitalization, and repeat revascularization after 12 months. RESULTS: A total of 1331 consecutive patients with CLI were treated using BTK PTA and 135 (10.1%) were approached with the pedal-plantar loop technique in order to recanalize the foot arteries. Target lesions were mostly occlusive and diffusely diseased, involving in most cases the tibial arteries as well as the in-flow and out-flow vessels. Acute success was achieved for tibial PTA in 100% of the cases, with ability to position and inflate the balloon and achieve adequate angiographic results without peri-procedural complications in all, whereas acute success for the pedal-plantar loop technique was 85%. Clinical improvement in functional status was obtained and maintained after an average of 12 months, with a significant improvement of transcutaneous oxygen tension after 15 days, 59+/-16 mmHg in the group of patients in which the foot arteries revascularization was successfully feasible, versus 42+/-12 mmHg in patients achieving patency of two BTK vessels at the ankle level with partial out-flow in the foot (P<0.001). CONCLUSIONS: Percutaneous revascularization of foot arteries in patients with CLI is feasible and safe, and appears to provide positive clinical results at both acute and mid-term follow-up.

Prognostic value of 64-slice coronary angiography in diabetes mellitus patients with known or suspected coronary artery disease compared with a nondiabetic population.

PURPOSE: This study aimed to determine the prognostic value of coronary angiography with multislice computed tomography (MSCT) in a population of diabetic subjects with known or suspected ischaemic heart disease compared with a nondiabetic control population. MATERIALS AND METHODS: Forty-nine patients with type 2 diabetes mellitus (DM) [group 1; mean age 67.7+/-8.8 years; 32 men; mean body mass index (BMI) 28+/-3.9] and 49 patients without DM (group 2, with similar demographic and clinical characteristics) were studied with MSCT coronary angiography to exclude the presence of ischaemic coronary artery disease (CAD). Each group comprised 26 patients (53%) with no history of ischaemic coronary disease and 23 patients (47%) with a history of myocardial infarction and/or myocardial revascularisation. Clinical follow-up was performed by analysing correlations between the rate of cumulative cardiac events (cardiac death, nonfatal myocardial infarction, unstable angina, and myocardial revascularisation), the severity of CAD identified on MSCT, and the presence of DM as a cardiovascular risk factor. RESULTS: At mean follow-up of 20 months, univariate analysis of survival showed significant differences between the two groups (group 1 vs. group 2, p=0.046). Moreover, the cumulative cardiac event rate correlated significantly with the presence of significant CAD (>50% stenosis) in both groups (group 1: p=0.003; group 2: p=0.0004). CONCLUSIONS: Event-free survival is significantly lower in the diabetic population compared with the normal control population (p=0.046) and is closely correlated with the presence of significant CAD. MSCT is an effective method for stratifying such risk and, together with high diagnostic accuracy, provides additional prognostic value.

Prevalence and characteristics of coronary artery disease in a population with suspected ischemic heart disease using CT coronary angiography: correlations with cardiovascular risk factors and clinical presentation.

PURPOSE: This study was undertaken to describe the correlation between the distribution of coronary artery disease (CAD) in a symptomatic population with suspected ischaemic heart disease, cardiovascular risk factors (RF) and clinical presentation. MATERIALS AND METHODS: we studied 163 patients (mean age 65.5 years; 101 men and 62 women) referred for multidetector computed tomography coronary angiography (MDCT-CA) to rule out CAD. The patients had no prior history of revascularisation or myocardial infarction. We analysed how the characteristics of CAD (severity and type of plaque) can change with the increase in RF and how they are related to different clinical presentations. RESULTS: patients were divided into three groups according to the number of RF: zero or one, two or three, and four or more. The percentage of coronary arteries with no plaque, nonsignificant disease and significant disease was 55%, 41% and 4%, respectively, in patients with zero or one RF; 27%, 51% and 22%, respectively, in patients with two or three RF; and 19%, 38% and 44%, respectively, in patients with four or more RF. Plaque in patients with nonsignificant disease was mixed in 65%, soft in 18% and calcified in 17%. The percentage of coronaries with no plaque in the three RF groups was 50%, 20% and 0% in patients with typical chest pain and 46%, 24% and 12% in those with atypical pain. The percentage of significant disease in patients with typical pain was 0%, 47% and 86% and in those with atypical pain 4%, 20% and 29%. CONCLUSIONS: MDCT plays an important role in the identification of CAD in patients with suspected ischaemic heart disease. Severity and type of disease is highly correlated with RF number and assumes different characteristics according to clinical presentation.