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Background Carotid endarterectomy (CEA) represents a standard procedure in case of symptomatic carotid stenosis of 50–99% within 2 weeks from onset of stroke or transient ischemic attack (TIA) symptoms. The optimal time to perform CEA after intravenous thrombolysis (IVT) is still unclear. The aim of this study was to analyze the safety of CEA performed within 2 weeks from IVT. Materials and methods A consecutive series of 70 patients affected by symptomatic carotid stenosis have been treated as per the international guidelines during 3 years. Eleven (15.7%) patients have been treated with IVT before CEA for ischemic stroke; remaining 59 (84.3%) patients received only CEA. CEA was performed in median 8 days (range: 2–13) after IVT. We examined the grade of disability before and after surgery as well as at 3 months follow-up, using the modified Ranking Scale (mRS). Results Among the patients who underwent CEA + IVT, CEA was performed in median 8 days (range: 2–13) after IVT. One patient received CEA within 48 hours from IVT, 3 patients within 72 hours, and 7 patients within 2 weeks. The complications within 90 days from surgery, in CEA + IVT group, were 3 cases of intracerebral hemorrhage (ICH) without symptoms. In patients who received only CEA, the complications were 1 case of stroke and 2 cases of ICH. The mortality registered was 0% in both groups. Among CEA + IVT group at 90 days after surgery, 9 patients had a mRS grade of 0–2, 2 patients had mRS of 3–5. Conclusions In our series, IVT before CEA did not seem to increase the rate of complications. However, the study has several limitations, and further studies must be performed before solid evidence is available for recommendations regarding the timing of CEA after IVT.

To compare unassisted and CAD-assisted detection and time efficiency of radiologists in reporting lung nodules on CT scans taken from patients with extra-thoracic malignancies using a Cloud-based system. Three radiologists searched for pulmonary nodules in patients with extra-thoracic malignancy who underwent CT (slice thickness/spacing 2 mm/1.7 mm) between September 2015 and March 2016. All nodules detected by unassisted reading were measured and coordinates were uploaded on a cloud-based system. CAD marks were then reviewed by the same readers using the cloud-based interface. To establish the reference standard all nodules ≥ 3 mm detected by at least one radiologist were validated by two additional experienced radiologists in consensus. Reader detection rate and reporting time with and without CAD were compared. The study was approved by the local ethics committee. All patients signed written informed consent. The series included 225 patients (age range 21–90 years, mean 62 years), including 75 patients having at least one nodule, for a total of 215 nodules. Stand-alone CAD sensitivity for lesions ≥ 3 mm was 85% (183/215, 95% CI: 82–91); mean false-positive rate per scan was 3.8. Sensitivity across readers in detecting lesions ≥ 3 mm was statistically higher using CAD: 65% (95% CI: 61–69) versus 88% (95% CI: 86–91, p

The treatment of cystic fibrosis (CF) patients homozygous for the F508del mutation with Orkambi®, a combination of a corrector (lumacaftor) and a potentiator (ivacaftor) of the mutated CFTR protein, resulted in some amelioration of the respiratory function. However, a great variability in the clinical response was also observed. The aim of this study was to evaluate the response to Orkambi® in a small cohort of F508del/F508del patients (n = 14) in terms of clinical and laboratory parameters, including ex vivo CFTR activity in mononuclear cells (MNCs), during a 12-month treatment. Patients responded with an increase in percent predicted forced expiratory volume in 1 s (FEV1%) and body mass index (BMI) as well as with a decrease in white blood cell (WBC) total counts and serum C-reactive protein (CRP) levels, although not significantly. Sweat chloride and CFTR-dependent chloride efflux were found to decrease and increase, respectively, as compared with pre-therapy values. CFTR and BMI showed a statistically significant correlation during Orkambi® treatment. Clustering analysis showed that CFTR, BMI, sweat chloride, FEV1%, and WBC were strongly associated. These data support the notion that CFTR-dependent chloride efflux in MNCs should be investigated as a sensitive outcome measure of Orkambi® treatment in CF patients.

Supplemental Digital Content is available in the text., Background and Purpose: We aimed to investigate the rate of hospital admissions for cerebrovascular events and of revascularization treatments for acute ischemic stroke in Italy during the coronavirus disease 2019 (COVID-19) outbreak. Methods: The Italian Stroke Organization performed a multicenter study involving 93 Italian Stroke Units. We collected information on hospital admissions for cerebrovascular events from March 1 to March 31, 2020 (study period), and from March 1 to March 31, 2019 (control period). Results: Ischemic strokes decreased from 2399 in 2019 to 1810 in 2020, with a corresponding hospitalization rate ratio (RR) of 0.75 ([95% CI, 0.71–0.80] P

The Chapman psychosis-proneness scales—also known as Wisconsin schizotypy scales (WSS)—are among the most used tools to measure schizotypy. The factor structure of the short-form WSS was investigated in a mixed sample of patients with chronic mental disorders and of healthy subjects from the general population. One hundred patients with a chronic mental disorder were enrolled over a 6-month period. For each patient, two controls of same sex and similar age (±5 years) were enrolled; 131 accepted to take part in the study. The unidimensional, the correlated four-factor, the second-order two-factor models, and the bifactor model with two or four orthogonally independent factors of the short-form WSS were tested with confirmatory factor analysis. Good reliability of the short-form WSS was confirmed, as its capacity of differentiating people with and without schizotypy. The bifactor models were superior to other models. However, in both bifactor models the explained common variance (ECV) attributable to the general factor and the percentage of uncontaminated correlations (PUC) were too low to use a general summary score as a measure of a single latent schizotypy variable. Symptoms scores derived from the short-form WSS can be better appreciated within a multidimensional model of schizotypy.

BACKGROUND Ivacaftor is a significant innovation in the treatment of cystic fibrosis (CF) with gating mutations. A substantial percentage of patients with CF have severe lung involvement, but these patients are usually excluded from phase III clinical trials. Thus, the effectiveness of ivacaftor in this population has not been fully determined. METHODS Data were collected from Italian CF centers with patients enrolled in an ivacaftor compassionate use programme (percent predicted [pp] forced expiratory volume in 1 second [FEV1 ]

Few mutations in cis have been annotated for F508del homozygous patients. Southern Italy patients who at a first analysis appeared homozygous for the F508del mutation (n=63) or compound heterozygous for the F508del and another mutation in the cystic fibrosis transmembrane conductance regulator gene (n=155) were searched for the A238V mutation in exon 6. The allelic frequency of the complex allele [A238V;F508del] was 0.04. When the whole data set was used (comprised also of 56 F508del/F508del and 34 F508del/other mutation controls), no differences reached the statistical significance in the clinical parameters, except chloride concentrations which were lower in [A238V;F508del]/other mutation compared with F508del/other mutation (P=0.03). The two study groups presented less complications than the control groups. Within the minimal data set (34 F508del/F508del, 27 F508del/other mutation, 4 [A238V;F508del]/F508del cases and 5 [A238V;F508del]/other mutation cases); that is, presenting all the variables in each patient, forced expiratory volume in 1 s and forced vital capacity presented a trend to lower levels in the study groups in comparison with the F508del/F508del group, and C-reactive protein approximated statistically significant higher levels in the [A238V;F508del]/other mutation as compared with F508del/F508del patients (P=0.09). The analysis of statistical dependence among the variables showed a significant anticorrelation between chloride and body mass index in the [A238V;F508del]/other mutation group. In conclusion, the complex allele [A238V;F508del] seems to be associated with less general complications than in the control groups, on the other hand possibly giving a worse pulmonary phenotype and higher systemic/local inflammatory response. These findings have implications for the correct recruitment and clinical response of F508del patients in the clinical trials testing the new etiological drugs for cystic fibrosis.

Follow-up aims to precociously identify recurrences, metastases or treatment-related adverse events so as to undertake the appropriate therapy. Guidelines admit lack of knowledge on optimal surveillance schedule, but suggest follow-up based on experts' opinion and risk stratification. To identify the impact, if any, of regular follow-up, we interrogated our prospectively collected database whether early detection of recurrences affected both clinical management and, likely, the outcome.We required information to be available on primary surgery and ≥3°years of follow-up for non-recurring patients. We analysed recurrence characteristics (asymptomatic versus symptomatic, low- versus high tumour burden) and computed tomography (CT) scan counts to detect one recurrence. Kaplan-Meier method estimated recurrence-free survival (RFS), post-recurrence progression-free survival (PR-PFS), and disease-specific overall survival (OS). Comparisons used Hazard ratios (HR) with 95% confidence intervals (CIs). Multivariate analyses employed the Cox proportional hazards model. All tests were two-sided.Between 01/2001 and 12/2012 we found 233 study-eligible patients. Estimated 5- and 10-year RFS were 61.8% and 50.4%, respectively. After a 68-month median follow-up, we observed 94 (40.3%) recurrences [73/94 (77.7%) asymptomatic versus 21/94 (22.3%) symptomatic and 45/94 (47.9%) low- versus 49/94 (52.1%) high tumour burden]. Multivariate analysis revealed that symptomatic and high tumour burden recurrences were highly predictive of both worse PR-PFS (HR:3.19, P 0.001; HR:2.80, P = 0.003, respectively) and OS (HR:3.65, P 0.001; HR:2.38, P = 0.026, respectively). Finally, 29 second (primary) cancers were detected during follow-up.Regular follow-up detects recurrences at an earlier stage and may be associated with a better PR-PFS and OS for these patients. In the absence of randomised trials, these evidences support follow-up effort and cost.

Aim The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) potentiator ivacaftor (Kalydeco®) improves clinical outcome in G551D cystic fibrosis (CF) patients. Here, we have investigated whether ivacaftor has a clinical impact on non-G551D gating mutations and function of circulating leukocytes as well. Methods Seven patients were treated with ivacaftor and evaluated at baseline, and at 1-3 and 6 months. Besides clinical and systemic inflammatory parameters, circulating mononuclear cells (MNC) were evaluated for CFTR-dependent chloride efflux by spectrofluorimetry, neutrophils for oxidative burst by cytofluorimetry and HVCN1 mRNA expression by real time PCR. Results Ivacaftor determined a significant decrease in sweat chloride concentrations at all time points during treatment. Body mass index (BMI), FEV1, and FVC showed an increasing trend. While C-reactive protein decreased significantly at 2 months, the opposite behavior was noticed for circulating monocytes. CFTR activity in MNC was found to increase significantly at 3 and 6 months. Neutrophil oxidative burst peaked at 2 months and then decreased to baseline. HVCN1 mRNA expression was significantly higher than baseline at 1-3 months and decreased after 6 months of treatment. The chloride efflux in MNC correlated positively with both FEV1 and FVC. On the other hand, sweat chloride correlated positively with CRP and WBC, and negatively with both respiratory function tests. A cluster analysis confirmed that sweat chloride, FEV1, FVC, BMI, and MNC chloride efflux behaved as a single entity over time. Discussion In patients with non-G551D mutations, ivacaftor improved both chloride transport in sweat ducts and chloride efflux in MNC, that is, functions directly imputed to CFTR.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) may involve many target organs with relevant variability among affected individuals. We performed a multi-organ assessment tapping nervous system, skeletal muscle and cardiovascular system in thirty-nine individuals belonging to 16 families from Central Italy sharing the same R1006C CADASIL mutation. Stroke prevalence was larger in female patients (66.7%) than in males (23.8%); high levels of CKemia were quite frequent (21.6%) and were related to a myopathy without mitochondrial alterations; several individuals had atrial septal aneurysm (10.3%). No specific relationships between common cardiovascular risk factors and clinical manifestations were found. The present systematic study thus identified several gender-related, myopathic and cardiovascular peculiarities of R1006C mutation. This kind of comprehensive approach is necessary to define clinical course, prognosis and treatment options for a multi-organ disease such as CADASIL.

Abnormally viscous bronchial secretions, a characteristic feature of cystic fibrosis (CF), may trap bacteria and fungi, allowing transient or chronic lung colonization. We report here a case of persistent Scedosporium apiospermum colonization in a patient with CF, who subsequently developed a lung mycetoma, and died with neurological symptoms suggestive of cerebral fungal involvement. Six isolates from consecutive sputum samples were molecularly typed by random amplification of polymorphic DNA (RAPD) using primers UBC701, UBC703, and GC70. Moreover, in vitro susceptibility of these isolates to current antifungals (amphotericin B, itraconazole, voriconazole, posaconazole, caspofungin and anidulafungin) was investigated by means of both E-test and CLSI methods. Antifungal susceptibility testing showed low minimum inhibitory concentration values only for triazole drugs. However, a unique genotype was isolated over a 12-month period, despite antifungal treatment with voriconazole for three months. This case report illustrates the therapy-refractory feature of this fungus, and provides new evidence that, as already reported, once a genotype of S. apiospermum has established colonization, it seems not to be replaced by others.

The aim of this study was to assess the effectiveness and safety of percutaneous vertebroplasty, a new technique for the treatment of vertebral pain deriving from fracture or gross osteolytic lesion due to multiple myeloma spinal involvement.Spinal osteolytic lesions are frequently associated with hematologic malignancies due to primary localization of disease (multiple myeloma and rarely lymphoma) or secondary effect of intensive corticosteroid therapy.We treated 64 patients (34 males, 30 females; mean age 71.4+/-9.6 y) with pain refractory to conventional medical therapy (analgesics, bed-rest, bracing with orthopedic devices for more than 3 wk) localized in spine, in the absence of neurologic signs.This treatment generated swift pain relief associated with an evident augmentation in vertebral resistance. Average preprocedural pain level for all patients was reported to be 8.04+/-1.4 whereas average pain level at 1 and 6 months follow-up period was 1.82+/-1.84 and 1.92+/-1.68, respectively. Although preprocedure and postprocedure demonstrated a statistically significant reduction in numeric pain scores (P0.01), the pain level at 1 and 6 months was not considered statistically significant. No procedure-related complications were observed in either leakages of polymethylmethacrylate in the epidural or foraminal area or in complications of pulmonary embolism for venous plexus involvement.Vertebroplasty is widely considered as an alternative, effective, simple, and safe technique in the treatment of neoplastic vertebral localizations consequent to hematologic malignancies. The same injection of polymethylmethacrylate can be executed before radiation therapy treatment, synergizing its delayed analgesic action to pain, after failure or in the case of local recurrences.

We genotyped three polymorphisms of the promoter region of the interleukin-10 (IL-10) gene in 220 CF patients from the CF Center of Bari, and tested for an association between genetic variants of the cytokine and chronic airway colonization with Pseudomonas aeruginosa. We found that carriers of the high-IL-10-producing-GCC haplotype had significantly higher risk of chronic pulmonary infection with the pathogen.

The aim of this study was to assess if percutaneous vertebroplasty (PVP) could relieve back pain, reduce drug consumption, and improve the mobility of patients with metastases and vertebral compression fractures. From August 2002 to July 2004, 283 patients (216 females; mean age: 73.8 +/- 9.9 years) underwent PVP on 749 vertebrae. Pain was evaluated with the pain intensity numeric rating scale (PI-NRS) (0 = no pain; 10 = worst pain) before the procedure and at the end point in September 2004 (follow-up:1-24 months; median: 7 months). A reduction of at least two points of the PI-NRS score was considered clinically relevant. Two hundred four patients were available for evaluation at the end point. Overall results showed a reduction of the median pain score from 8 at baseline to 1 at the end point (p < 0.0001); a clinically relevant pain reduction was observed in 176/205 patients (86%); 89/147 patients (61%) gave up a brace support (p < 0.0001); and 117/190 patients (62%) gave up drug therapy. Results were similar in different subgroups stratified according to age, underlying pathology, number of fractured or treated vertebrae, and length of follow-up. This study adds evidence that PVP is effective in treating painful vertebral fractures. A significant reduction in drug assumption and significant mobility improvement can also be achieved.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common hereditary cerebral small vessel disease, is caused by mutations in the NOTCH3 gene on chromosome 19. Clinical manifestations of CADASIL include recurrent transient ischemic attacks, strokes, cognitive defects, epilepsy, migraine and psychiatric symptoms. Parkinsonian features have variably been reported in CADASIL patients, but only a few patients showed a clear parkinsonian syndrome. We studied two patients, a pair of monozygotic twins, carrying the R1006C mutation of the NOTCH3 gene and affected by a parkinsonian syndrome. For the first time in CADASIL patients, we used transcranial sonography (TCS) to assess basal ganglia abnormalities. TCS showed a bilateral hyperechogenic pattern of substantia nigra in one twin, and a right hyperechogenic pattern in the other. In both patients, lenticular nuclei showed a bilateral hyperechogenic pattern, and the width of the third ventricle was slightly increased. The TCS pattern found in our CADASIL patients is characteristic neither for Parkinson's disease, nor for vascular parkinsonism and seems to be specific and related to the disease-specific pathological features.

Background and Purpose— To describe parkinsonism as a clinical manifestation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Methods— We report 5 patients carrying the R1006C mutation in the exon 19 of NOTCH3 gene. All cases presented late onset, slowly progressive parkinsonism, not responsive to l-dopa. We performed brain MRI and 123 I-FP-CIT SPECT in all and in 3 additional patients carrying the same mutation but without parkinsonism. Four patients with parkinsonism underwent myocardial 123 I-meta-iodobenzylguanidine scintigraphy. Results— In all patients, brain MRI showed widespread ischemic lesions in the periventricular white matter, the internal and external capsules, the basal ganglia, and thalami. 123 I-FP-CIT SPECT showed symmetrical or asymmetrical reduction of tracer uptake in the putamen, with inconstant caudate involvement. Myocardial 123 I-meta-iodobenzylguanidine scintigraphy resulted normal. Nigrostriatal denervation was also demonstrated in 2 patients without parkinsonism. Conclusions— In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, parkinsonism may be a not rare, late onset manifestation. The clinical picture, the lack of response to dopaminergic treatment, and MRI findings suggest a vascular parkinsonism, which may be preceded by a protracted presymptomatic phase.

We report the case of a patient with an apparent homozygosity for the D1152H mutation located in exon 18 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The parents had no personal history of cystic fibrosis (CF) and referred to our laboratory after the diagnosis of fetal bowel hyperechogenicity. The proband presented with meconium ileus and normal sweat chloride test. Sequencing of the CFTR exon 18 together with quantitative genomic assays, such as real-time PCR and the multiplex ligation probe amplification (MLPA) techniques, were performed and revealed that the father was heterozygous for the D1152H mutation and the mother carried a large deletion of the CFTR gene encompassing the genomic sequence including the same mutation. The child inherited D1152H from his father and the large deletion of the CFTR gene from his mother. We suggest that D1152H likely acts as a mild mutation with a dominant effect on the severe deletion of exon 18, considering that after 3 years of clinical examinations the child shows no classical signs and symptoms of CF. Not testing for large deletions in subjects with apparent homozygosity for a mutated CFTR allele could lead to the misidentification of CFTR mutation carrier status.

In seeking more specific biomarkers of the cystic fibrosis (CF) lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibiotic treatment. Genes involved in neutrophil-mediated inflammation, i.e. chemotaxis, respiratory burst, apoptosis, and granule exocytosis, were the targets of this study. Microarray analysis was carried out in blood and airway neutrophils from CF patients and in control subjects. A fold change (log) threshold of 1.4 and a cut-off of p

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic disorder caused by mutations in the NOTCH3 gene, with a striking variability in phenotypic expression. To date, only two homozygous patients have been reported, with divergent phenotypic features. We describe an Italian CADASIL patient, homozygous for G528C mutation, in whom early manifestation of the disease was migraine, but whose clinical evolution was characterized by a reversible acute encephalopathy followed by full recovery ("CADASIL coma"). Clinical evaluation, MR scan, neuropsychological and neurophysiological investigation did not reveal substantial differences between our homozygous patient and her heterozygous relatives sharing the same mutation, or between our patient and a group of heterozygous individuals with the same mutation but from different families. Skin biopsy identified peculiar features in the homozygous patient, with cytoplasmic pseudoinclusions likely containing granular osmiophilic material (GOM) in the vascular smooth muscle cells, but further studies are necessary to substantiate their possible relationships with CADASIL homozygosis. "CADASIL coma" did not seem to be specific of patient's homozygosis, since it was observed in one of her heterozygous relatives, whereas its pathogenesis seems to be related to peculiar constellations of unknown predisposing factors. The present study demonstrated that CADASIL conforms to the classical definition of dominant diseases, according to which homozygotes and heterozygotes for a defect are phenotypically indistinguishable.

This study was designed to assess the clinical outcomes of patients treated by vertebral augmentation with nitinol endoprosthesis (VNE) to treat painful vertebral compression fractures.Forty patients with one or more painful osteoporotic VCF, confirmed by MRI and accompanied by back-pain unresponsive to a minimum 2 months of conservative medical treatment, underwent VNE at 42 levels. Preoperative and postoperative pain measured with Visual Analog Scale (VAS), disability measured by Oswestry Disability Index (ODI), and vertebral height restoration (measured with 2-dimensional reconstruction CT) were compared at last follow-up (average follow-up 15 months). Cement extravasation, subsequent fractures, and implant migration were recorded.Long-term follow-up was obtained in 38 of 40 patients. Both VAS and ODI significantly improved from a median of 8.0 (range 5-10) and 66 % (range 44-88 %) to 0.5 (range 0-8) and 6 % (range 6-66 %), respectively, at 1 year (p0.0001). Vertebral height measurements comparing time points increased in a statistically significant manner (ANOVA, p0.001). Overall cement extravasation rate was 9.5 %. Discal and venous leakage rates were 7.1 and 0 % respectively. No symptomatic extravasations occurred. Five of 38 (13.1 %) patients experienced new spontaneous, osteoporotic fractures. No device change or migration was observed.VNE is a safe and effective procedure that is able to provide long-lasting pain relief and durable vertebral height gain with a low rate of new fractures and cement leakages.

Background It is not known whether antibiotic therapy for lung disease in cystic fibrosis (CF) has an influence on circulating polymorphonuclear neutrophil (PMN) function and apoptosis. Patients and methods Blood PMNs were obtained from 14 CF patients before and after antibiotic treatment for an acute exacerbation, and from 10 healthy controls. PMNs were evaluated for production of reactive oxygen species (ROS) by spectrophotometry, of cytokines in the conditioned medium by ELISA, and apoptotic response by cytofluorimetry. Results ROS and interleukin (IL)-8 were produced at higher levels by CF PMNs pre-therapy than control PMNs under basal conditions. IL-8 levels further increased after therapy. Early apoptotic response was higher in CF PMNs pre-therapy than in control PMNs, and this pattern did not change after antibiotic treatment. Conclusions Circulating PMNs are primed in CF acute patients. Further studies are needed to consider PMN-produced IL-8 as a biomarker to evaluate response to antibiotic therapy in CF patients.

To assess long-term clinical outcome of percutaneous vertebroplasty (PV).PV was performed in 1,634 patients (1,387 women; median age 73 years ± 9.3) with painful osteoporotic vertebral compression fractures (VCFs). All patients had back pain that persisted for ≥ 2 months with a concordant magnetic resonance imaging study. After PV, medical therapy for osteoporosis was continued, and patients were prospectively evaluated (follow-up 11.8-44.9 months, mean 25.0 months). Visual analog scale (VAS), Oswestry Disability Index (ODI), analgesic drug use, and use of external brace support were recorded at baseline and during follow-up. New occurrences of symptomatic vertebral fractures were recorded.The mean VAS score of 7.94 significantly improved to 1.12 at the primary endpoint (P.001). Differences in patterns of analgesic usage compared with baseline values were highly statistically significant (marginal homogeneity test, P.001). Median ODI values of 82% before treatment significantly decreased to 6% (P.001). Before intervention, 1,279 patients wore a brace; 1,167 (91.2%) patients did not wear a brace after PV (χ(2) = 31.005, P.0001). A new painful fracture with a significant higher proportion of contiguous vertebrae (63.6%) occurred in 214 (13.1%) patients (z = 7.59, P = .025).PV can provide durable pain relief and improvement in ambulation in patients with VCFs.

Congenital intrahepatic portosystemic shunts are rare hepatic vascular anomalies that often lead to severe secondary conditions. A 6-year-old boy was referred for assessment of severe hypoxia, and a large liver mass was diagnosed with such a malformation and was managed by direct closure of the venous fistula by interventional radiology. Follow-up assessment shows normalization of the respiratory condition and a progressive reduction of the vascular liver lesion. Review of literature suggests that radiologic interventions are currently the criterion standard for managing these conditions, with surgery reserved for patients who are not eligible for radiologic procedure and those requiring liver transplantation.

Percutaneous vertebroplasty (PV) is a minimally invasive procedure involving the injection of bone cement within a collapsed vertebral body. Although this procedure was demonstrated to be effective in osteoporosis and metastases, few studies have been reported in cases of multiple myeloma (MM). We prospectively evaluated the safety and efficacy of PV in the treatment of vertebral compression fractures (VCFs) resulting from MM. PV was performed in 106 consecutive MM patients who had back pain due to VCFs, the treatment of which had failed conservative therapies. Follow-up (28.2 ± 12.1 months) was evaluated at 7 and 15 days as well as at 1, 3, 6, 12, 18, and every 6 months after PV. Visual analog scale (VAS) pain score, opioid use, external brace support, and Oswestry Disability Index (ODI) score were recorded. The median pretreatment VAS score of 9 (range 4–10) significantly (P

A case of a 75-year-old patient with a painful pathologic humeral shaft fracture, with unacceptably high surgical risk and unsatisfactory analgesia is reported. In this case, impaired arm function and persistent pain with conservative management resulted in a poor quality of life. Palliation with image-guided percutaneous osteoplasty was considered. Because of potential cement leakage, inadequate fracture reduction, the site of the fracture, and the mobility of the joints in that area, image-guided percutaneous delivery of metallic bone marrow nails implanted together with polymethyl methacrylate (PMMA) osteoplasty was performed. This procedure achieved humeral shaft stabilization, bone fragment alignment, fracture reduction, and pain relief.

This study is a survey of cardiovascular risk factors in Sardinia in the years 1999-2001 and allows us to update previously observed trends of such factors and to compare them with those in the Italian mainland.Random samples of free living population of the Mediterranean island of Sardinia, Italy, were collected. Overall, 6818 subjects, 50% of each sex, and aged 20-80+ years constituted the sample. Personal and family data were collected using a semiquantitative questionnaire of frequencies. Blood biochemical variables related to risk for atherosclerosis were measured. In particular, serum total cholesterol, HDL-cholesterol, triglycerides, Apo A-1, Apo B, Lp(a), uric acid, blood glucose and plasma homocysteine were analyzed in each subject enrolled.In the age classes 20-59 years, during a 30 year period, prevalence of smoking among males continued to decrease from 58 to 24% (p for trend0.001), and, for the first time, prevalence of smoking among females decreased as well: from 31% in 1995 to 20% in 2001 (p for trend0.001). In contrast, a steady increase in TC (mg/dl) (189, 206, 215, 216, p for trend0.05 in males and 184 197, 212, 217, p for trend0.05 in females), and LDL-C (136, 143, 138, 144, p for tend0.05 in males and 127, 139, 136, 135, p for trend0.05 in females) was observed. HDL-C showed a steady increase (p for trend0.01 in males and females). Lp(a) values were high in both sexes, a finding linked to the ethnic influence on them. Systolic and diastolic blood pressure values (mm Hg) increased with age. In the present survey (population aged 20-80+ years, current smokers were 17.5% among males and 13.8% among females. Total and HDL-cholesterol were higher than in other parts of Italy (209 vs 205 in males, and 211 vs 204 in females), while systolic and diastolic blood pressure were lower.Overall, total- and LDL-cholesterol showed an increasing trend, while blood pressure and smoking habits had a decreasing tendency. The increase in blood cholesterol follows the trend in other areas of the world, mainly due to changing dietary habits. Therefore, a campaign of eating information and education (population strategy) could favourably modify cardiovascular risk, as occurred in Sardinia during the past decade with the Regional ATS-Sardegna Campaign.

The aim of this study was to assess the feasibility of and venous leakage reduction in percutaneous vertebroplasty (PV) using a new high-viscosity bone cement (PMMA). PV has been used effectively for pain relief in osteoporotic and malignant vertebral fractures. Cement extrusion is a common problem and can lead to complications. Sixty patients (52 female; mean age, 72.2 +/- 7.2) suffering from osteoporosis (46), malignancy (12), and angiomas (2), divided into two groups (A and B), underwent PV on 190 vertebrae (86 dorsal, 104 lumbar). In Group A, PV with high-viscosity PMMA (Confidence, Disc-O-Tech, Israel) was used. This PMMA was injected by a proprietary delivery system, a hydraulic saline-filled screw injector. In Group B, a standard low-viscosity PMMA was used. Postprocedural CT was carried out to detect PMMA leakages and complications. Fisher's exact test and Wilcoxon rank test were used to assess significant differences (p < 0.05) in leakages and to evaluate the clinical outcome. PV was feasible, achieving good clinical outcome (p < 0.0001) without major complications. In Group A, postprocedural CT showed an asymptomatic leak in the venous structures of 8 of 98 (8.2%) treated vertebrae; a discoidal leak occurred in 6 of 98 (6.1%). In Group B, a venous leak was seen in 38 of 92 (41.3%) and a discoidal leak in 12 of 92 (13.0%). Reduction of venous leak obtained by high-viscosity PMMA was highly significant (p < 0.0001), whereas this result was not significant (p = 0.14) related to the disc. The high-viscosity PMMA system is safe and effective for clinical use, allowing a significant reduction of extravasation rate and, thus, leakage-related complications.

Lung disease and Pseudomonas aeruginosa (P. aeruginosa) airway colonization represent a major cause of morbidity and mortality in cystic fibrosis (CF). Human beta-defensin (hBD)-1 is believed to play an important role in mucosal innate immunity in the lung. This study aimed to investigate whether three single-nucleotide polymorphisms (SNPs) in the 5'-untranslated region of DEFB1, G-52A, C-44G and G-20A were associated with P. aeruginosa airway colonization in CF. A total of 224 CF patients and 196 control subjects were studied. DEFB1 SNPs were characterized by restriction fragment length polymorphisms. Patients' sputum samples were collected and analyzed by standard methods. Single SNP analysis suggested that CF patients carrying the -52AA and the -20GG genotypes had a higher rate of P. aeruginosa airway colonization than patients homozygous and heterozygous for the -52G and -20A alleles (P=0.01 and P=0.007, respectively). A significant association between the ACG haplotype and chronic P. aeruginosa infection was also identified (odds ratio (95% confidence interval): 3.00 (1.42-6.36), P=0.004). These results indicate that variant alleles in DEFB1 might contribute to the colonization of P. aeruginosa in CF.

The aim of this study was to assess the efficacy of percutaneous cementoplasty (PC) with polymethylmethacrylate (PMMA) in painful extravertebral lytic bone metastases not responding to conventional therapy. Fifty patients (25 females), mean age 64.7 +/- 11.2 years, underwent PC after giving informed consent. Procedures were performed under fluoroscopy (1/50) or combined fluoroscopy-CT (49/50) guidance in local anesthesia or under deep sedation in 7 patients with large metastases who underwent radiofrequency thermoablation (RFA) in the same session. Seventy lesions were treated (1-6 per patient; average, 1.4 +/- 0.9), arranging in size from 1 to 10 cm (average, 3.6 +/- 2.1 cm). Mean volume of PMMA per lesion was 5.9 +/- 3.2 ml (range, 1.5-15.0 ml). Pain was prospectively evaluated on an 11-point visual analog scale (VAS) before and after the procedure (follow-up, 15 to 36 months). Mean VAS score dropped from 9.1 +/- 1.2 (range: 6-10) to 2.1 +/- 2.5 (range: 0-9). Mean VAS difference was 7.0 +/- 2.3 (range, 1-10; p \ 0.0001, Wilcoxon signed rank test). Forty-seven of the 50 patients (94%) suspended narcotic drugs, in 22 (44%) pain was controlled with a nonsteroidal anti-inflammatory drug, in 25 (50%) analgesic therapy was suspended, and 13 of 50 (26%) had complete pain regression. In 3 of the 50 patients (6%) pain was not improved. No statistical difference between osteoplasty and osteoplasty plus RFA was found (p = 0.8338, Mann-Whitney test). No complications arose during the procedure. Two patients with metastases in the femoral diaphysis reported a fracture 1 month after treatment. PC is effective to obtain pain regression in painful bone metastases not responding to conventional analgesic therapy; bone consolidation cannot be obtained in the diaphysis of long weight-bearing bones.

To assess the effectiveness of airway stenting performed exclusively under radiological guidance for the palliation of malignant tracheobronchial strictures. We report our experience in 16 patients with malignant tracheobronchial stricture treated by insertion of 20 Ultraflex self-expandable metal stents performed under fluoroscopic guidance only. Three patients presented dysphagia grade IV due to esophageal malignant infiltration; they therefore underwent combined airway and esophageal stenting. All the procedures were performed under conscious sedation in the radiological room; average procedure time was around 10 min, but the airway impediment never lasted more than 40 sec. We obtained an overall technical success in 16 cases (100%) and clinical success in 14 patients (88%). All prostheses were successfully placed without procedural complications. Rapid clinical improvement with symptom relief and normalization of respiratory function was obtained in 14 cases. Two patients died within 48 hr from causes unrelated to stent placement. Two cases (13%) of migration were observed; they were successfully treated with another stent. Tumor overgrowth developed in other 2 patients (13%); however, no further treatment was possible because of extensive laryngeal infiltration. Tracheobronchial recanalization with self-expandable metal stents is a safe and effective palliative treatment for malignant strictures. Airway stenting performed exclusively under fluoroscopic view was rapid and well tolerated.

Currently, more than 1,000 mutations have been identified in the cystic fibrosis transmembrane regulator (CFTR) gene. While some mutations are common worldwide, the majority are restricted in certain ethnic groups. We have found that in Southern Italy, the 852del22 mutation is well represented with a frequency of 3.5%. We have screened, by reverse dot blot, denaturing gradient gel electrophoresis (DGGE), and gene sequencing, the entire coding regions of CFTR gene in 371 consecutive cystic fibrosis (CF) patients from Southern Italy and have identified 17 patients carrying rare genotypes, among which 13 [6 M; median age 21.7 years (range: 4.5–47.7 years)] carry the 852del22 mutation. To assess the phenotypic expression of CF in patients with the 852del22 mutations we have compared these patients with a group of age and gender matched patients homozygous for the ΔF508 mutation [n = 34; 19 M; median age 19.9 years (range: 3.8–34.6 years)]. Overall, we found no difference in terms of complications, patient survival (17.6% vs. 30.7%; P = NS), estimated time needed to develop a severe lung disease (22.1 vs. 24.5 years; P = NS), nutritional status, and rate of infection or colonization by most common pathogens between patients in the two groups. Finally, we have found that a late diagnosis was associated with a poor outcome (severe lung disease) regardless of genotype. Our data show that 852del22 mutation results in a phenotypic expression of disease as severe as that determined by the more typical ΔF508 and, as in the latter case, there is no strict genotype/phenotype correlation. © 2005 Wiley-Liss, Inc.

Vascular dementia is usually sporadic and associated with definite risk factors. Several cases also occur in a familial fashion, and may affect middle-aged or even younger subjects. Recently, an autosomal dominant inheritance was demonstrated in two unrelated French families, the members of which were affected by stroke-like episodes culminating in progressive dementia. Genetic linkage analysis assigned the disease locus to chromosome 19q12. We report an additional kindred of Italian origin in which at least 16 subjects presented leukoencephalopathic alterations. Recurrent strokes, psychiatric disturbances, dementia, and in 2 members, tetraplegia and pseudobulbar palsy were the hallmarks of this syndrome. Notably, 5 asymptomatic individuals had neuroradiological signs of leukoencephalopathy. Pathological examination of 1 subject revealed a widespread vasculopathy of the perforating arterioles, characterized by deposition of eosinophilic-congophilic material that did not immunostain with antibodies against prion protein, beta-amyloid, cystatin C, transthyretin, or heat-shock protein 70 and was similar to that described in the French families. Based on the maximum lod score, the most likely location for the disease locus was also mapped to chromosome 19q12, and found to coincide with the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) locus. The present results confirm the existence of a nosologically distinct, autosomal dominant cerebrovascular disease, presenting with recurrent subcortical ischemic strokes independent of vascular risk factors.

Background: Vertebral metastases are associated with significant pain, disability, and morbidity. Open surgery for fracture stabilization is often inappropriate in this cancer population due to a poor risk-benefit profile, particularly if life expectancy is short. Vertebroplasty and kyphoplasty are appealing adjunctive procedures in patients with malignancy for alleviation of intractable pain. However, these patients have a higher risk of serious complications, notably cement extravasation. Study Design: We prospectively evaluated clinical results of polyetheretherketone (PEEK) implant (Kiva) assisted vertebroplasty performed in malignant painful osteolytic lesions at risk for cement extravasation due to vertebral wall involvement. Setting: Department of Interventional Radiology, Institute for Cancer Research and Treatment, Candiolo, Turin, Italy Methods: Forty patients (22 women; mean age 66.8 ± 12.4), suffering from a painful spine malignancy with vertebral wall involvement not responding to conventional therapies and without surgical indications, underwent vertebral augmentation with Kiva intravertebral implant for pain palliation. The procedure was performed with moderate sedation and local anesthesia under combined digital fluoroscopy and computed tomography guidance. After the coil-shaped PEEK implant was deployed within the vertebral lesion, bone cement was injected under continuous digital fluoroscopic control. Patients were discharged from the hospital the next procedural day. The Visual Analog Scale (VAS) for pain, Oswestry Disability Index (ODI), analgesic requirement, and use of external brace support were evaluated to determine efficacy. The primary end-point was safety and efficacy at one month after the procedure. However, all the patients were scheduled to be followed-up at month 3, 6, and every 6 months thereafter. Follow-up was prospectively evaluated in all patients after Kiva with clinical interviews. The Institution’s Internal Review Board approved this study. Results: Median pre-treatment VAS of 10 (range 6 – 10) significantly (P < 0.001) dropped to one (range 0 – 3), with all patients achieving a clinically relevant benefit on pain at one month. Differences in pre- and post-treatment analgesic therapy were significant (P < 0.001). All patients no longer use an external brace after Kiva. In 7 out of 43 (16.3%) treated vertebrae a bone cement leakage was detected. Limitations: This is a not randomized study. Participants were limited to 40 patients. Conclusion: The Kiva System potentially represents a novel and effective minimally invasive treatment option for patients suffering from severe pain due to osteolytic vertebral metastases. Key words: Vertebroplasty, metastases, pain palliation, Kiva, spine