Comparison between different referral strategies for acute ischemic stroke patients in a hub-spoke emergency stroke network: a real-world experience in south-east Lazio.

AIM: To describe different referral strategies for acute ischemic stroke (AIS) patients in a Hub-Spoke emergency stroke network with their incidence, time metrics and related outcomes. METHODS: Referral paradigms were defined as follows: primary transfer to the comprehensive stroke center (CSC) from a remote region, called mothership (MS); secondary transfer to the CSC from a primary stroke center where intravenous thrombolysis was available, called drip and ship (DS); secondary transfer to the CSC from a community hospital where no reperfusion therapy was available, called ship and drip (SD); primary transfer to the CSC from its catchment area, called direct CSC (dCSC). RESULTS: Among 517 anterior circulation AIS patients treated with mechanical thrombectomy between 2015 and 2020, 16.6% of them were SD, in addition to the well-known referral paradigms of MS (21.8%) and DS (18.1%). This rate grew to 30% when only patients whose place of onset was outside the CSC catchment area were considered. In the SD group, onset to CSC and onset to groin were significantly longer (178±80 min vs. 102±60 min, p<0.001, and 277±77 min vs. 211±61 min, p<0.001, respectively), and the risk of any intracranial hemorrhage (ICH) was significantly higher (OR: 2.514; 95%CI: 1.18-5.35, p=0.017) compared to MS. CONCLUSION: In this hub-spoke stroke network, a high proportion of SD paradigm was found, which was associated with longer times to treatment and higher rates of any ICH. A closer cooperation between hospital stroke physicians, national health system staff, and paramedics is warranted to identify the most appropriate referral strategy for each patient.

Functional and radiological outcomes after bridging therapy versus direct thrombectomy in stroke patients with unknown onset: Bridging therapy versus direct thrombectomy in unknown onset stroke patients with 10-point ASPECTS.

BACKGROUND AND PURPOSE: The aim was to assess functional and radiological outcomes after bridging therapy (intravenous thrombolysis plus mechanical thrombectomy) versus direct mechanical thrombectomy (MT) in unknown onset stroke patients. METHODS: A cohort study was conducted on prospectively collected data from unknown onset stroke patients who received endovascular procedures at ≤6 h from symptom recognition or awakening time. RESULTS: Of the 349 patients with a 10-point Alberta Stroke Program Early Computed Tomography Score (ASPECTS), 248 received bridging and 101 received direct MT. Of the 134 patients with 6-9-point ASPECTS, 123 received bridging and 111 received direct MT. Each patient treated with bridging was propensity score matched with a patient treated with direct MT for age, sex, study period, pre-stroke disability, stroke severity, type of stroke onset, symptom recognition to groin time (or awakening to groin time), ASPECTS and procedure time. In the two matched groups with 10-point ASPECTS (n = 73 vs. n = 73), bridging was associated with higher rates of excellent outcome (46.6% vs. 28.8%; odds ratio 2.302, 95% confidence interval 1.010-5.244) and successful recanalization (83.6% vs. 63%; odds ratio 3.028, 95% confidence interval 1.369-6.693) compared with direct MT; no significant association was found between bridging and direct MT with regard to rate of symptomatic intracerebral hemorrhage (0% vs. 1.4%). In the two matched groups with 6-9-point ASPECTS (n = 45 vs. n = 45), no significant associations were found between bridging and direct MT with regard to rates of excellent functional outcome (44.4% vs. 31.1%), successful recanalization (73.3% vs. 76.5%) and symptomatic intracerebral hemorrhage (0% vs. 0%). CONCLUSIONS: Bridging at ≤ 6 h of symptom recognition or awakening time was associated with better functional and radiological outcomes in unknown onset stroke patients with 10-point ASPECTS.

Treatment of peripheral arterial disease in diabetes: a consensus of the Italian Societies of Diabetes (SID, AMD), Radiology (SIRM) and Vascular Endovascular Surgery (SICVE).

Diabetic foot (DF) is a chronic and highly disabling complication of diabetes. The prevalence of peripheral arterial disease (PAD) is high in diabetic patients and, associated or not with peripheral neuropathy (PN), can be found in 50% of cases of DF. It is worth pointing out that the number of major amputations in diabetic patients is still very high. Many PAD diabetic patients are not revascularised due to lack of technical expertise or, even worse, negative beliefs because of poor experience. This despite the progress obtained in the techniques of distal revascularisation that nowadays allow to reopen distal arteries of the leg and foot. Italy has one of the lowest prevalence rates of major amputations in Europe, and has a long tradition in the field of limb salvage by means of an aggressive approach in debridement, antibiotic therapy and distal revascularisation. Therefore, we believe it is appropriate to produce a consensus document concerning the treatment of PAD and limb salvage in diabetic patients, based on the Italian experience in this field, to share with the scientific community.

Endovascular radiofrequency renal denervation in treating refractory arterial hypertension: a preliminary experience.

PURPOSE: This study was done to investigate the efficacy and safety of percutaneous renal denervation with the Symplicity catheter for reducing blood pressure in patients with essential hypertension resistant to medical therapy (systolic blood pressure >160 mmHg despite the use of three or more antihypertensive drugs, including a diuretic). MATERIALS AND METHODS: In September 2010, five patients affected by essential hypertension resistant to medical therapy were treated. All patients were studied by computed tomography angiography (CTA) of the renal arteries before the procedure and underwent follow-up at 30 and 60 days with colour Doppler ultrasound (CDUS) with evaluation of resistive index, glomerular filtration rate (GFR), 24-h blood pressure and serum catecholamine concentration. Student's t test was used to assess the effectiveness of the procedure in lowering blood pressure. RESULTS: In treated patients, mean blood pressure at baseline was 171/100 mmHg [standard deviation (SD) ± 8/10]; mean GFR was 91.6 ml/min/1.73 m(2) (SD ± 15). Blood pressure after the procedure was reduced by -18/-5 and -13/-10 mmHg at 30 and 60 days, respectively, with a mean medication reduction of 3.6. No complications occurred during the intra- or periprocedural period or during short-term follow-up. CONCLUSIONS: The Symplicity system proved to be efficacious and without serious adverse events in reducing blood pressure and antihypertensive medication use in patients affected by essential hypertension resistant to medical therapy. Although encouraging, our data are preliminary and need to be validated by larger prospective randomised studies.

Prevalence study of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: preliminary data.

PURPOSE: This study aimed to evaluate the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS). MATERIAL AND METHODS: From November 2009 to February 2010, 74 participants (40 MS patients and 34 healthy controls) were enrolled in a randomised singleblind prospective study. All participants underwent ultrasonography (US) to detect signs of CCSVI. RESULTS: CCSVI was detected in 55% of patients in the MS group and 35% in the control group; the difference was not statistically significant (p=0.089). CONCLUSIONS: In our experience, a slight difference exists in the prevalence of CCSVI between MS and healthy controls, but it is not as yet clear which parameters may be most significant. This preliminary study failed to show a statistically significant difference in the prevalence of CCSVI among patients affected by MS. It did, however, reveal a tendency that requires a larger number of patients to achieve statistically significant results.

Acute stroke treatment using the Penumbra endovascular mechanical thrombolysis device: a single-centre experience.

PURPOSE: Ischaemic stroke due to occlusion of large cerebral vessels has a poor prognosis. The clinical outcome is related to efficacy and timing of recanalisation of the occluded arteries. We report our experience with a thrombus aspiration device (Penumbra), and focus on pre- and postprocedural management. MATERIALS AND METHODS: We retrospectively reviewed 18 consecutive patients with acute ischaemic stroke due to the occlusion of large cerebral vessels who were treated with mechanical thrombolysis at our centre between September 2009 and July 2010. Preprocedural symptoms were quantified using the National Institutes of Health Stroke Scale (NIHSS). Mechanical thrombolysis was performed with the Penumbra system. Intravenous thrombolysis was done only if <3 h had elapsed since symptom onset. Associated vessel stenoses were treated with stenting. All patients underwent neurological examination and postprocedural magnetic resonance angiography (MRA) at 3 and 6 months. RESULTS: Mechanical thrombolysis using the Penumbra system was performed in all cases. A total of 83% of treated vessels had a value of 2/3 according to the Thrombolysis in Cerebral Infarction (TICI) scale. In seven patients (39%) intravenous thrombolysis was unsuccessful, and salvage mechanical thrombolysis followed. Three patients died after the procedure (16.7%). Five patients (27.8%) required a stenting procedure. All patients reported a significant improvement in symptoms (mean baseline NIHSS 19.6±5.6; mean postprocedural NIHSS, 7.8±5.5 p<0.0001) CONCLUSIONS: Our preliminary experience with the Penumbra mechanical thrombolysis system confirms previously reported results showing the efficacy and safety of the device in treating acute stroke caused by the occlusion of large intracranial vessels.

Case report of a successful multidisciplinary approach to a giant scrotal malformation.

INTRODUCTION: Congenital pelvic malformations are rare and represent a difficult therapeutic challenge. Scrotal arteriovenous malformations are quite unusual, with only a few such cases reported in the literature. Only one case of scrotal malformation? due to an arteriovenous fistula resulting in azoospermia has been described. PRESENTATION OF CASE: The two-phase strategy adopted in that case permitted complete treatment of a large-sized malformation that was served by 4 main blood confluences. DISCUSSION: Angio-CT performed using reconstructions with MIP and SSD algorithms provided more detailed data about the extension of the afferents and efferents of the arteriovenous malformation, thus enabling us to plan the endovascular treatment of the lesion. CONCLUSION: A multidisciplinary approach is mandatory to achieve good results in these cases.

Applicability and clinical results of percutaneous transluminal angioplasty with a novel, long, conically shaped balloon dedicated for below-the knee interventions.

AIM: The aim of this study was to assess the feasibility, safety and efficacy of percutaneous transluminal angioplasty (PTA) in patients with critical limb ischemia (CLI) using a novel balloon designed for below-the-knee (BTK) indications. METHODS: The authors have prospectively collected baseline, periprocedural and mid-term data of all consecutive patients with CLI due to BTK disease in which PTA was attempted using a long (210 mm), conically-shaped balloon (0.5 mm tapering from proximal to distal balloon edges). The primary objective was the assessment of acute success (composite of technical, angiographic and procedural success). The secondary assessments included limb salvage rate, major (above the ankle) and minor (below the ankle) amputation, change in Rutherford class and cutaneous oxygen tension, reocclusion/restenosis, rehospitalization, and repeat revascularization after one year. RESULTS: A total of 31 patients were treated with 36 long tapered balloons. Ten patients presented with ischemic tissue loss. Target lesions were mostly occlusive and diffuse, commonly involving the tibial arteries as well as the in-flow and out-flow vessels. Acute success was achieved in 100% of the cases without periprocedural complications. Clinical improvement in functional status was obtained and maintained after an average of 12 months, with a significant (P<0.001) decrease in Rutherford class, 100% limb salvage, no major amputation and five (16.1%) minor amputations. Duplex ultrasound control showed restenosis/reocclusion in two (6.5%) cases, whereas a total of seven (22.6%) patients underwent repeat revascularization (2 [6.5%] target lesion re-PTA). CONCLUSIONS: Infra-popliteal PTA with this new, BTK dedicated, long tapered balloon in patients with CLI was feasible and safe, and was associated favorable clinical results at both acute and mid-term follow-up.

The endovascular management of open aortic surgery complications with emergency stent-graft repair in high-risk patients.

The aim of the study was to demonstrate the utility of endovascular stent-graft repair for emergency management of aorto-iliac surgery complications. Between 1997 and 2004, in our institute, 201 patients underwent transluminal endovascular graft placement. In 3 patients (1.4%), previously submitted to conventional aortic surgery, endovascular treatment was carried out due to the occurrence of late complications: 1 secondary aortocaval fistula, 1 impending rupture of aortic pseudoaneurysm and 1 secondary aorto-enteric fistula. All candidates were high surgical risk patients (ASA III-IV) suitable for endoprosthesis positioning by endovascular stent-graft implantation presenting with severe worsening conditions in an emergency situation. The patients were treated under local anesthesia and mild sedation. After treatment there was complete resolution of the clinical presentation and an improvement of general conditions in all 3 patients. In the 1(st) patient legs edema disappeared and in the 2(nd) patient mesogastric pain is absent, respectively at 30 and 8 months. The 3(rd) patient, with secondary aorto-enteric fistula, was submitted 2 months later to aortic graft removal and axillo-bifemoral bypass because of infection development. For the treatment of abdominal aortic surgery complications in high risk patients, particularly in emergency situations, endovascular approach is a feasible and safe alternative to conventional open repair. Further evaluation of this technique and longer follow-up will determine its exact role in the management of these life-threatening complications.

CT Angiography ASPECTS Predicts Outcome Much Better Than Noncontrast CT in Patients with Stroke Treated Endovascularly.

BACKGROUND AND PURPOSE: Noncontrast CT ASPECTS has been investigated as a predictor of outcome in patients with acute ischemic stroke. Our purpose was to investigate whether CTA source images are a better predictor of clinical and radiologic outcomes than NCCT ASPECTS in candidates for endovascular stroke therapy. MATERIALS AND METHODS: CT scans of patients (n = 124) were independently evaluated by 2 readers for baseline NCCT and CTA source image ASPECTS and for follow-up ASPECTS. An mRS of ≤2 at 3 months was considered a favorable outcome. Receiver operating characteristic curve analysis was used to assess the ability of NCCT and CTA source image ASPECTS to identify patients with favorable outcomes. A stepwise multiple regression analysis was performed to find independent predictors of outcome. RESULTS: Baseline CTA source image ASPECTS correlated better than NCCT ASPECTS with follow-up ASPECTS (r = 0.76 versus r = 0.51; P for comparison of the 2 coefficients < .001). Receiver operating characteristic curve analysis showed that baseline CTA source image ASPECTS compared with NCCT ASPECTS can better identify patients with favorable outcome (CTA source image area under the curve = 0.83; 95% CI, 0.76-0.91; NCCT area under the curve = 0.67; 95% CI, 0.58-0.77; P < .001). Finally, the stepwise regression analysis showed that lower age, good recanalization, lower time to recanalization, and good baseline CTA source image ASPECTS, not NCCT ASPECTS, were independent predictors of favorable outcome. CONCLUSIONS: CTA source image ASPECTS predicts outcome better than NCCT ASPECTS; this finding suggests CTA rather than NCCT as a main step in the decision-making process for patients with acute ischemic stroke.

Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators.

Digitalis, diuretics and vasodilators are considered the standard therapy for patients with congestive heart failure, for which treatment is tailored according to the severity of the syndrome and the patient profile. Apart from the clinical seriousness, heart failure is always characterized by an energy depletion status, as indicated by low intramyocardial ATP and coenzyme Q10 levels. We investigated safety and clinical efficacy of Coenzyme Q10 (CoQ10) adjunctive treatment in congestive heart failure which had been diagnosed at least 6 months previously and treated with standard therapy. A total of 2664 patients in NYHA classes II and III were enrolled in this open noncomparative 3-month postmarketing study in 173 Italian centers. The daily dosage of CoQ10 was 50-150 mg orally, with the majority of patients (78%) receiving 100 mg/day. Clinical and laboratory parameters were evaluated at the entry into the study and on day 90; the assessment of clinical signs and symptoms was made using from two-to seven-point scales. The results show a low incidence of side effects: 38 adverse effects were reported in 36 patients (1.5%) of which 22 events were considered as correlated to the test treatment. After three months of test treatment the proportions of patients with improvement in clinical signs and symptoms were as follows: cyanosis 78.1%, oedema 78.6%, pulmonary rales 77.8%, enlargement of liver area 49.3%, jugular reflux 71.81%, dyspnoea 52.7%, palpitations 75.4%, sweating 79.8%, subjective arrhytmia 63.4%, insomnia 662.8%, vertigo 73.1% and nocturia 53.6%. Moreover we observed a contemporary improvement of at least three symptoms in 54% of patients; this could be interpreted as an index of improved quality of life.

Controlled clinical trial of imidazole.2-hydroxybenzoate (ITF 182) versus sulindac in patients with rheumatoid arthritis.

The efficacy and safety of the nonsteroidal anti-inflammatory drugs imidazole.2-hydroxybenzoate and sulindac were compared in 30 patients with classical or definite rheumatoid arthritis. The trial was designed as a randomized parallel-group study comprising 15 patients given imidazole.2-hydroxybenzoate and 15 given sulindac orally for 28 days. Patients in both groups improved significantly in almost all of the variables evaluated. Imidazole.2-hydroxybenzoate was more effective than sulindac on Ritchie's articular index, left hand proximal interphalangeal joint circumference, erythrocyte sedimentation rate, and C-reactive protein. The incidence of side effects was significantly higher in patients treated with sulindac.

The effect of simvastatin on HDL cholesterol in hyperlipidemic patients. Evidence of a relationship with the changes in serum triglyceride level.

The main effect of simvastatin is the decrease of serum cholesterol due to the reduction of LDL. A decrease of serum triglycerides and an increase of HDL-C are commonly observed during the treatment. The reduction of triglycerides is accounted for by the increased catabolism of apo B-containing lipoproteins whereas the mechanisms bringing about the increase of HDL-C are still unknown. We treated 318 patients with primary hyperlipidemia (227 with phenotype IIa and 91 with phenotype IIb) with simvastatin 10 mg a day and after 6 weeks we found a mean 3% increase in HDL-C. HDL-C increased only in about half of the patients and the patients in whom HDL-C increased had baseline higher serum triglycerides and had a greater hypotriglyceridemic response than patients in whom HDL-C did not increase. Accordingly, HDL-C increased in type IIb patients who experienced a greater change in triglycerides than type IIa patients, in whom HDL-C did not increase significantly. Apo A-I levels did not change and apo A-I/HDL-C ratio significantly decreased. At a daily dose of 40 mg, administered to 51 treatment-resistant patients, simvastatin produced a marginally greater decrease in serum cholesterol and LDL-C, but not in serum triglycerides and HDL-C, than at the daily dose of 10 mg. An increase in HDL-C was associated with a reduction in serum triglycerides. The decrease in apo A-I/HDL-C ratio suggests that the increase in HDL-C after simvastatin must be regarded as an enrichment of the cholesterol core of HDL particles. The effect is likely to be due to the decrease of the serum concentration of VLDL bringing about a reduction of cholesterol transfer from apo A-I to apo B-containing lipoproteins.

Normal and slow-release formulations of bezafibrate: a comparative pharmacokinetic study in man.

In this study the pharmacokinetics of a new slow-release formulation of bezafibrate (a hypolipaemic drug) were evaluated in a group of six healthy volunteers. In the first part of the study the bioavailability of this formulation was compared to the normal preparation of bezafibrate. In the second part of the experiment the possible accumulation was studied. The subjects were administered the slow-release preparation at 08h00 for seven consecutive days. The resulting data indicate that the slow-release formulation shows a lower dispersion of Tmax values. There was an increase of the plasma half-life from 1.9 to 5.5 h, but a possibility of accumulation could be excluded.

Anionic glycoproteins and their hexosamine content in neoplastic patients: relationships with the clinical stage and the course of the disease.

In 40 healthy subjects, in 47 non-cancer patients, and in 142 cancer patients, perchloric acid soluble glycoproteins (PASG) and hexosamines were determined to investigate their tumor specificity and correlation with the tumor mass. Cancer patients were divided into three subgroups: CI, no evidence of cancer (after radical surgery); CII, locoregional disease; CIII, widespread metastatic disease. There was no statistically significant difference in PASG among normals, non-cancer and CI patients; hexosamines in non-cancer and in CI patients were higher (P less than 0.002) than in normals; both PASG and hexosamines were significantly higher in CII and CIII patients than in normals (P less than 0.001). In the CI group, 62% of patients who relapsed within 10 months after surgery had high hexosamine values, whereas 69% of patients who did not relapse showed normal levels (P less than 0.05). PASG and hexosamines significantly increased with cancer progression and decreased when objective response to treatment was achieved. They are not tumor specific, but seem to be related to the tumor burden; hexosamines seem to have some prognostic value.

Effects of intravenous high doses of ketoprofen on blood clotting, bleeding time and platelet aggregation in man.

The effect of ketoprofen (Orudis, Farmitalia) on ADP, epinephrine (EPI) and collagen (COLL) induced platelet aggregation (PlA), simplate bleeding time (SBT), partial thromboplastin time (PTT) and per cent prothrombin activity (PrA) was studied in eleven patients, four males and seven females (median age 59 years) with rheumatoid arthritis (six cases), cancer (four cases) and osteoarthrosis (one case). Tests were performed before and 1, 8 and 24 hours after a single intravenous dose (600 mg) of ketoprofen and on Days 4 and 8 during a 7-day treatment (200 mg i.v. every 8 hours) and 1 day after withdrawal of the drug. PTT and PrA were not affected by the drug. Bleeding time was not significantly modified by the acute treatment, but was prolonged during the subacute course, though it was not different from baseline values at the end of the trial. Significant reduction of platelet aggregation was seen in both acute and subacute conditions with complete or almost complete recovery 36 hours after the last dose. It is concluded that ketoprofen affects platelets with readily reversible inhibition of in vitro aggregation and a slight increase of bleeding time.

[Ileo-cecal malignant carcinoid tumor with orbital metastases as initial symptoms. Anatomo-clinical study]. / Carcinoide maligno ileo-ciecale esordito con metastasi orbitarie. Studio anatomo-clinico.

A case of carcinoid tumor of the last ileal loop is presented; the first clinical sign was exophthalmos due to bilateral orbital metastases. The case is believed to be the third recorded one of carcinoid with metastases to the orbit; other metastatic lesions were located in myocardium, liver, spleen, kidney, ovary and trachea. Porgressive hirsutism was present in association with the somewhat atypical clinical picture.

[Significance of certain neoplastic markers in a series of patients with lung cancer]. / Significato di alcuni marcatori di neoplasia in una casistica di pazienti affetti da carcinoma polmonare.

Perchloric acid soluble proteins (PPS) and their content of N-acetylneuraminic acid (NANA) may serve as valuable tumor markers for a variety of malignant neoplasms. To evaluate their clinical significance, PPS, NANA and carcino-embryonic antigen (CEA) were measured in 32 patients with lung cancer. High PPS (greater than or equal to 0,73 mg/ml) and NANA (greater than or equal to 96 micrograms/ml) levels occurred in 8 of 50 (16%) healthy volunteers and respectively in 22% and 54% of patients. CEA levels were high (greater than or equal to 3 ng/ml) in 1 out of 21 (5%) healthy volunteers and in 83% of the patients; 84% of the patients showed an elevation of NANA and of CEA. The highest values of the three markers seem to be associated with extensive disease but no statistically significant difference has emerged from the comparison of patients with limited disease with the ones with extensive involvement. Changes of the tumor mass correlate with changes of serum levels of PPS, NANA and CEA. It is concluded that CEA determination is clinically valuable in lung cancer, while PPS and NANA do not provide greater information.

First dose and steady state pharmacokinetics of nimesulide and its 4-hydroxy metabolite in healthy volunteers.

The pharmacokinetics of nimesulide (4-nitro-2-phenoxymethane-sulfonanilide, NMS), a non-steroidal antiinflammatory drug, and of its 4-hydroxy metabolite (4-nitro-2-(4'-hydroxy-phenoxy)-methane sulfonanilide, OH-NMS) was studied after a single oral dose (200 mg) and after repeated treatments (100 mg every 12 hours for 7 days) of NMS to two groups of 12 healthy volunteers. Plasma concentrations of NMS and OH-NMS were followed for 48 hours after the single dose and up to the 12th hour on the 1st day and on the 7th day during repeated treatment. After the single dose of 200 mg peak plasma concentrations of the drug (9.85 micrograms/ml) were reached at 3.17 hours and the half-life during the elimination phase was 4.95 hours. The metabolite reached highest plasma levels (3.03 micrograms/ml) at 5.33 hours and its apparent half-life was similar to that of the parent drug (4.78 hours). NMS plasma levels on the 7th day, predicted from the results of the 1st day, were similar to the measured values. The pharmacokinetics of NMS or OH-NMS after single or repeated dose was not time or dose dependent.

[Hematoma and pulmonary contusion as a consequence of closed injury of the thorax in childhood]. / L'ematoma e la contusione polmonare quale conseguenza di trauma chiuso del torace in età pediatrica.

A personally observed case of internal chest injury is described with emphasis on the clinical and radiological features of the contusion and lung haematoma produced and the relative therapeutic problems.