Francesca Iacoponi

Grading Carotid Intrastent Restenosis: A 6-Year Follow-Up Study

Background and Purpose— The accuracy of carotid ultrasound has not been well established in predicting intrastent restenosis (ISR) after carotid artery stenting (CAS). The aim of this study is to determine different degrees of ISR using ultrasound velocity criteria compared to percentage of stenosis at angiography. Methods— This is a 6-year prospective study. After CAS procedure, each patient underwent angiography for measuring ISR (NASCET method) which was compared to peak systolic velocity (PSV), end diastolic velocity (EDV), and the ratio between PSV of internal carotid artery and common carotid artery (ICA/CCA). This was done within 48 hours, thus creating a baseline value. Ultrasound (US) examination was performed at day 30, at 3, 6, 9, and 12 months, and then yearly. Patients with an increase in PSV greater than 3 times the baseline value or in presence of PSV ≥200 cm/s underwent angiography. Results— 814 CAS procedures, 6427 US examinations, and 1123 angiographies were performed. ISR ≥70% and ISR ≥50% was detected, respectively, in 22 patients and in 73 patients. We defined velocity criteria for grading carotid ISR: PSV ≤104 cm/s, if <30% stenosis; PSV:105 to 174 cm/s if 30% to 50% stenosis; PSV:175 to 299 cm/s if a 50% to 70% stenosis; PSV ≥300 cm/s, EDV ≥140 cm/s, and ICA/CCA ≥3.8 if a ≥70% stenosis. Receiver operator characteristic (ROC) curves for ISR ≥70% were, respectively, for PSV, EDV, and ICA/CCA: 0.99, 0.98, and 0.99. Conclusions— US grading of carotid ISR can guarantee a correct follow-up after CAS if new customized velocity criteria are validated by skilled operators using a specific protocol of follow-up in a certified laboratory.

Siena Carotid Artery Stenting Score. A Risk Modelling Study for Individual Patients

Background and Purpose— Carotid artery stenting (CAS) still entails a considerable peri-interventional risk of serious neurological adverse events. The aim of this study was to generate a score to grade this risk for CAS in individual patients. Methods— This is a 9-year prospective study. Consecutive patients with ≥70% carotid artery stenosis were treated with a standardized CAS procedure. All patients included underwent independent neurological evaluation before and after the procedure and at 30 days. The rates of transient ischemic attack and minor, major, and fatal stroke were recorded. Stroke predictors were analyzed and a score system was generated using Arabic numerals for all variables to preoperatively grade the individual patient risk of stroke. Results— Two thousand one-hundred twenty-four successful CAS procedures were performed. The transient ischemic attack and minor, major, and fatal stroke rates at 30 days were, respectively, 2.72% (n=60), 1.55% (n=33), 1.18% (n=25), and 0.61% (n=13). Multiple regression analysis showed that the following significantly predicted the 30-day risk of treatment-related stroke: cardiac disease, symptomatic patient, diabetes, calcification or ulceration at the level of the lesion, native and ostial lesion, lesion length >15 mm, the need for predilatation, type III arch, bovine arch, arch calcification, procedure time >30 minutes, and the operators experience of <50 CAS procedures. The operators experience of >100 CAS procedures was the only protective factor against the development of stroke at 30 days (odds ratio, 0.81; confidence interval, 0.67–0.95). The Siena CAS score was developed from these variables and predicted the risk of CAS within the 3 categories of low risk (<1%; CAS I), medium risk (1% to 3%; CAS II), and high risk (>3%; CAS III), with a sensitivity of 0.82 and specificity of 0.79. Conclusions— The Siena CAS risk score seems to be a useful tool to help predict stroke after CAS but needs to be validated in independent cohorts at a variety of centers before it can be recommended for application, preferably in a randomized comparison with carotid endarterectomy.

Short- and long-term effects of spa therapy in knee osteoarthritis.

Fioravanti A, Iacoponi F, Bellisai B, Cantarini L, Galeazzi M: Short- and long-term effects of spa therapy in knee osteoarthritis. Objective:To assess both the short- and long-term effectiveness of spa therapy in patients with primary knee osteoarthritis in a prospective, randomized, single-blinded, controlled trial. Design:Eighty outpatients were enrolled in this study; 40 patients were treated with a combination of daily local mud packs and bicarbonate-sulfate mineral bath water from the spa center of Rapolano Terme (Siena, Italy) for 2 wks, and 40 patients continued regular, routine ambulatory care. Patients were assessed at baseline time; after 2 wks; after 3, 6, and 9 mos after the beginning of the study and were evaluated by Visual Analog Scale for spontaneous pain, Lequesne index, Western Ontario and McMaster Universities Index for gonarthrosis, Arthritis Impact Measurement Scale-1, and symptomatic drug consumption. Results:We observed a significant improvement of all evaluated parameters at the end of the cycle of spa therapy, which persisted throughout the whole of the follow-up period, whereas in the control group no significant differences were noted. This symptomatic effect was confirmed by the significant reduction of symptomatic drug consumption. Tolerability of spa therapy seemed to be good, with light and transitory side effects. Conclusions:The results from our study confirm that the beneficial effects of spa therapy in patients with knee osteoarthritis lasts over time, with positive effects on the painful symptomatology and a significant improvement on functional capacities. Spa therapy can represent a useful backup to pharmacologic treatment of knee osteoarthritis or a valid alternative for patients who do not tolerate pharmacologic treatments.

Subintimal Angioplasty with the Aid of a Re-entry Device for TASC C and D Lesions of the SFA

AIM The aim of this prospective study was to assess the clinical effectiveness and related midterm patency of subintimal angioplasty (SAP) in patients suffering from critical limb ischaemia (CLI) in a single tertiary care university centre. The secondary aim was to evaluate the safety and clinical effectiveness of using a re-entry device when re-canalisation by SAP was unsuccessful. METHODS From January 2005 to December 2007, consecutive patients suffering from CLI (Rutherford clinical categories: 4-6) were treated with SAP. All patients included in the study had occluded SFA (TASC C and D) and underwent clinical and ultrasound follow-up examinations at day 30 and at 3, 6, 9 and 12 months, and then yearly. A re-entry device (Outback, Cordis Corporation, Miami Lakes, Florida, USA in all cases) was only used when re-canalisation by simple SAP was unsuccessful, and stenting was used when residual stenosis was >30% or there was a flow-limiting dissection. Factors that could modify the outcome were analysed. RESULTS In this study, 145 patients were treated, with a technical success rate of 83.5% (121 of 145) for simple SAP. Stenting was performed in 43% (n=62) of successful SAP procedures. No death occurred in the perioperative period, while the 30-day mortality was 4.8% (7 of 145). The re-entry device (Outback) was used in 24 cases (16.5%). The technical success of the re-entry device was 79% (19 of 24), with a 90% success rate of stent placement at the site of re-entry. Complications occurred in 6.2% of all procedures (n=9) (three arterial perforations (2.1%), three distal embolisations (2.1%), two femoral artery pseudo-aneurysms (1.4%) and one arterio-venous fistula (0.7%)). Factors capable of independently affecting the patency were renal insufficiency (p=0.03), current smoking (p=0.01) and diabetes (p=0.04). The primary patency at 1 and 3 years was 70% and 34% and the secondary patency at 1 and 3 years was 77% and 43%, respectively. At the same time intervals, the limb-salvage rate was 88% and 49%. CONCLUSIONS SAP with the aid of a re-entry device for TASC C and D lesions of the SFA seems to be safe and clinically effective in patients suffering from CLI, according to the experience at our centre. Further follow-up and more data are necessary to confirm these findings.

In vitro effect of gold and silver nanoparticles on human spermatozoa

The cytotoxicity of Au/Ag nanoparticles (NPs) on human spermatozoa was investigated in vitro. Semen from donors were incubated (37 °C, 60′–120′) with 30, 60, 125, 250 and 500 μM Au/Ag‐NPs. Sperm motility was evaluated following WHO guidelines; sperm viability was assessed with eosin Y test. Au‐NPs were characterised and localised with field emission gun‐based scanning transmission electron microscope/energy dispersive spectroscopy and transmission electron microscopy. Both tested NPs exerted a significant dose‐dependent effect on motility and viability of human spermatozoa (P < 0.001). Ag‐NPs seem to show a slightly elevated toxicity although not significant (P > 0.05). Au‐NPs were localised in spermatozoa, whereas Ag‐NPs were undetectable. In conclusion, Au‐NPs and Ag‐NPs do not appear to be harmful for human spermatozoa up to high concentrations (250–500 μM) that are probably difficult to reach in vivo. It is mandatory to explore the genotoxic effect of NPs in germ cells.

The diagnostic evaluation of patients with potential adult-onset autoinflammatory disorders: Our experience and review of the literature

Hereditary periodic fever syndromes (HPFSs) are a group of inherited disorders of the innate immune system caused by mutations of genes involved in the regulation or activation of the inflammatory response, which belong to the category of autoinflammatory disorders. Most HPFs typically have an onset in pediatric age, while a limited number of patients experience disease onset during adulthood. The relative rarity and lack of information on adult-onset autoinflammatory diseases make it likely that genetic testing is often inconclusive. Recently, we have identified a set of variables related to the probability of detecting gene mutations in MEFV, responsible for familial Mediterranean fever, and TNFRSF1A, responsible for tumor necrosis factor receptor-associated periodic syndrome. In addition, we have proposed a diagnostic score for identifying those patients at high risk of carrying mutations in these genes. However, before the score can be recommended for application, further evaluation by means of longitudinal studies on different ethnicities and different populations deriving from other geographical areas is needed in order to definitively verify both its sensitivity and its specificity. The present manuscript offers our suggestions on how to establish a differential diagnosis for adult-onset HPFs, as well as a review of the literature, and we also provide a score revision available online.

Validation of a diagnostic score for the diagnosis of autoinflammatory diseases in adults

Most autoinflammatory disorders typically come out in the pediatric population, although a limited number of patients may experience disease onset during adulthood. To date, a late disease onset has been described only in familial Mediterranean fever, caused by mutations in the MEFV gene, and in tumor necrosis factor receptor-associated periodic syndrome, caused by mutations in the TNFRSF1A gene. The relative rarity and lack of information on adult-onset autoinflammatory diseases make it likely that mutations will be found in an even smaller percentage of cases. With the aim of improving the genetic diagnosis in adults with suspected autoinflammatory disorders, we recently identified a set of variables related to the probability of detecting gene mutations in MEFV and TNFRSF1A and, in addition, we have also proposed a diagnostic score for identifying those patients at high risk of carrying mutations in these genes. In the present study we evaluated the preliminary score sensitivity and specificity on a wider number of patients in order to validate the goodness of fit of the model. Two hundred and nineteen consecutive patients with a clinical history of periodic fever attacks were screened for mutations in MEFV and TNFRSF1A genes; detailed information about family/personal history and clinical manifestations were also collected. For the validation of the score we considered data both from the 110 patients used to build the preliminary diagnostic score and from the additional 219 patients enrolled in the present study, for a total number of 329 patients. Early age at disease onset, positive family history for recurrent fever episodes, thoracic pain, abdominal pain and skin rash, which are the variables that had previously been shown to be significantly associated with a positive genetic test result (12), were used for validation. On univariate analysis the associations with a positive genetic test were: age at onset (odds ratio [OR] 0.43, p=0.003), positive family history for recurrent fever episodes (OR 5.81, p<0.001), thoracic pain (OR 3.17, p<0.001), abdominal pain (OR 3.80, p<0.001) and skin rash (OR 1.58, p=0.103). The diagnostic score was calculated using the linear combination of the estimated coefficients of the logistic multivariate model (cut-off equals to 0.24) revealing good sensitivity (0.778) and good specificity (0.718). In conclusion, our score may serve in the diagnostic evaluation of adult patients presenting with recurrent fever episodes suspected of having an autoinflammatory disorder, helping identify the few subjects among them who may be carriers of mutations in MEFV and TNFRSF1A genes.

Effect of quercetin, rutin, naringenin and epicatechin on lipid peroxidation induced in human sperm.

Quercetin, rutin, naringenin, epicatechin are flavonoids with diverse properties, including antioxidant potential. We evaluated, in vitro, the cytotoxicity of these flavonoids (20, 30, 50, 100, 200, 400 μM) in swim-up selected human sperm. Antioxidant activity was tested against tert-butylhydroperoxide induced lipid peroxidation using a C11-BODIPY(581/591) probe and transmission electron microscopy. A significant concentration-dependent effect on sperm viability (P<0.001) and motility (P<0.001) was observed. Lipid peroxidation was decreased in samples treated with 30 μM quercetin (P<0.01) and 30 μM rutin (P<0.05) versus samples incubated with tert-butylhydroperoxide alone. Naringenin (50-100 μM) showed a low protective effect and epicatechin (200 μM) was not efficacious. Transmission electron microscopy analysis confirmed the protective action of rutin and in particular quercetin on damages induced by lipid peroxidation. These results underlined the antioxidant properties of quercetin and rutin. A possible role of these compounds in the supplementation of media used during semen handling warrants attention and further studies.

Development and preliminary validation of a diagnostic score for identifying patients affected with adult-onset autoinflammatory disorders.

To date, the rate of detection of autoinflammatory gene mutations in patients suspected of having an autoinflammatory disorder is very low. However, most of these data refer to pediatric populations. The relative rarity and lack of information on adult-onset autoinflammatory diseases make it likely that mutations will be found in an even smaller percentage of cases. Our aim was to develop and validate a set of variables for predicting the risk that a given adult patient presenting with recurrent fever episodes carries mutations in the MEFV or TNFRSF1A genes, in order to increase the probability of obtaining positive results on genetic testing. One hundred and ten consecutive patients with a clinical history of periodic fever attacks were screened for mutations in the TNFRSF1A and the MEFV genes. The mean age at disease onset was 27.85 years. Detailed information about each patients family history, personal history, and clinical manifestations were retrospectively collected. A diagnostic score was constructed based on univariate and multivariate analysis in a randomly-selected dataset (training set; n=40). The score was validated on an independent set of the remaining patients (validation set; n=70). Age at onset (odds ratio [OR] 0.958, P = 0.050), positive family history of recurrent fever episodes (OR 5.738, P = 0.006), thoracic pain (OR 7.390, P = 0.002), abdominal pain (OR 2.853, P = 0.038) and skin involvement (OR 8.241, P = 0.003) were independently correlated with a positive genetic test result. A diagnostic score was calculated using the linear combination of the estimated coefficients of the logistic model (cut off equal to 0.24) revealing high sensitivity (0.94), high specificity (0.94) and high accuracy (0.94). We have identified variables that appear to be strongly related to the probability of detecting gene mutations in MEF and TNFRSF1A in adults, thus improving the evaluation of patients with suspected autoinflammatory disorders.

AAA with a Challenging Neck: Early Outcomes Using the Endurant Stent-Graft System

OBJECTIVES The efficacy and safety of endovascular aneurysm repair is disputable in aneurysms with a short, angulated, wide, conical, or thrombus-lined neck making a reliable seal difficult to achieve. The influence of a challenging neck on early results using the Endurant stent-graft system in high risk patients was investigated. MATERIALS AND METHODS A retrospective study conducted on a prospectively compiled database of 72 elective patients with challenging neck treated with the Endurant system (Endurant Stent Graft, Medtronic AVE, Santa Rosa, CA, USA). These patients were compared to a control group (n = 65) without significant neck problems. Endpoints were early technical and clinical success, deployment accuracy and differences in operative details at one month follow-up. Data are reported as mean and standard deviation or as absolute frequency and percentage (%). Normality distribution and homogeneity of variances were tested by Shapiro-Wilks and Levene tests, respectively. Inter-group comparisons for each variable were made by t-test or χ2-test or Fisher exact test. A p < 0.05 was considered statistically significant. RESULTS Mean age was 76.12 years; 76.6% were males. Risk factors and pre-operative variables did not differ significantly between the two groups. Mean neck length was 10.56 mm in patients with challenging anatomies and 22.85 mm in controls. Patients with a challenging neck differed significantly (p < 0.001) from controls in terms of mean infrarenal (37.67° vs. 20.12°) and suprarenal angle (19.63° vs. 15.57°); 82% of patients with a challenging neck were ASA III/IV (vs. 86%). Technical success was 100%, with four unplanned proximal extension in challenging group. No type I endoleaks or aneurysm-related deaths occurred in either group; major complications were 1.54% vs. 1.39% (p = 0.942). Operative details were similar in both groups. CONCLUSION Treatment with the Endurant stent-graft is technically feasible and safe, yielding satisfactory results even in challenging anatomies. Medium- and long-term data are needed to verify durability, but early results are promising.