Pregnancy effect on disease activity in women with multiple sclerosis treated with cladribine.

INTRODUCTION: Cladribine is an oral immune reconstitution therapy for relapsing multiple sclerosis (RMS). Hormonal and immune changes are responsible for the decline of disease activity in the third trimester of pregnancy and disease reactivation in the early post-partum period.We investigate the impact of pregnancy on disease activity in women with MS who conceived after cladribine treatment. METHODS: We recruited women of childbearing age with relapsing-remitting MS (RRMS) who became pregnant or not after being treated with cladribine. For both groups, demographic, clinical and radiological data were collected 1 year before and after treatment during a mean follow-up of 3.53 years. We compared disease activity over time between groups using variance analysis for repeated measures. RESULTS: 48 childbearing women were included. 25 women had a pregnancy after a mean of 1.75 years from the first treatment cycle. Women with or without pregnancy did not differ in demographics or pre-cladribine disease activity. No significant differences in disease activity or EDSS worsening were found between women with or without pregnancy. DISCUSSION: Our findings suggest that pregnancy does not appear to influence disease activity and disability in women previously treated with cladribine; further studies with larger numbers and longer follow-up are needed to confirm this finding.

Sexual dysfunction in multiple sclerosis: The impact of different MSISQ-19 cut-offs on prevalence and associated risk factors.

BACKGROUND: Although multiple sclerosis (MS) Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a widely applied tool, no unique definition of sexual dysfunction (SD) based on its score exists. OBJECTIVE: To explore the impact of different MSISQ-19 cut-offs on SD prevalence and associated risk factors, providing relevant information for its application in research and clinical settings. METHODS: After defining SD according to two different MSISQ-19 cut-offs in 1155 people with MS (pwMS), we evaluated SD prevalence and association with sociodemographic and clinical features, mood status and disability via logistic regression. RESULTS: Depending on the chosen cut-off, 45% to 54% of pwMS reported SD. SD defined as MSISQ-19 score >30 was predicted by age (OR=1.01, p=0.047), cognition (OR=0.96, p=0.004) and anxiety (OR=1.03, p=0.019). SD defined as a score >3 on any MSISQ-19 item was predicted by motor disability (OR=1.12, p=0.003) and cognition (OR= 0.96, p=0.002). CONCLUSION: Applying different MSISQ-19 cut-offs influences both the estimated prevalence and the identification of risk factors for SD, a finding that should be considered during study planning and data interpretation. Preserved cognition exerts a protective effect towards SD regardless from the specific study setting, representing a key point for the implementation of preventive and therapeutic strategies.

Ponesimod to treat multiple sclerosis.

Ponesimod (ACT-128800) is a directly bioavailable, rapidly reversible sphingosine-1-phosphate (S1P) receptor modulator, highly selective for the subtype 1 (S1P1 receptor). It acts by blocking the egress of lymphocytes from the lymphoid organs, thus limiting the entry of autoreactive cells into the central nervous system. Unlike fingolimod, ponesimod does not require monitoring of the first dose, thanks to a 14-day uptitration regimen, which markedly reduces the incidence of cardiodynamic effects related to the initiation of therapy. Results from the OPTIMUM phase III trial demonstrated the superiority of ponesimod over teriflunomide on disease activity markers, without unexpected safety concerns. Furthermore, the drug is eliminated within 1 week of discontinuation, allowing for the reversibility of its effects. Ponesimod was recently approved in both the U.S. and E.U. for the treatment of relapsing forms of multiple sclerosis. This review summarizes the pharmacological characteristics of ponesimod and the main studies that led to its approval.

Bilateral persistent sciatic artery in a 77-year-old woman: A case report.

Rare vascular anomaly, the persistent sciatic artery (PSA) has an extremely low incidence, likely 0.04%-0.06%. This vessel is prone to thrombosis, distal thromboembolization, rupture, and aneurysmal formation, while its symptoms can vary considerably, from completely asymptomatic pictures to cases with pain, claudication or ischemia of the lower limbs. It is essential to diagnose this anomaly in time, in order to avoid dangerous complications for the patient's life. The main methods of diagnosis are given by vascular ultrasound, CT, or MRI. Here we present a case of a bilateral PSA diagnosed in a 77-year-old woman as an incidental finding in angio-CT of the lower limbs.

Ethylene-vinyl alcohol polymer trans-arterial embolization in emergency peripheral active bleeding: initial experience.

AIM: The aim of this paper was to evaluate the efficacy, safety, and clinical outcomes of superselective embolization using ethylene-vinyl alcohol copolymer (Onyx Liquid Embolic System; ev3 Neurovascular, Irvine, CA, USA) as the primary treatment in active peripheral emergency arterial bleeding. METHODS: Between January 2014 and June 2014, all patients with active peripheral arterial bleeding who were treated by embolization were retrospectively analyzed. We selected 15 (age 37-91 year old) patients embolized with Onyx, chosen as embolic agent in an intention-to-treat fashion. Multidetector computed tomography was performed in all patients. RESULTS: Active bleeding was detected in all cases. Digital subtraction angiography confirmed CT findings in all cases. The causes of bleeding were traumatic in 8 patients, angiodysplasia in 1 patient, duodenal ulcer in 1, chronic pancreatitis in 1 and unknown in 4 patients. Nine patients were under anticoagulant or antiplatelet therapy. Embolization was possible in all patients. The technical success rate was 100%. The immediate bleeding control rate was 100%. No rebleeding at 30 days occurred (0%). There were no major complications, or deaths attributable to the treatment. No patient needed surgery or new embolization during a mean follow-up period of 5.1 months (range, 4.5-6 months). CONCLUSION: Control of massive active peripheral emergency arterial bleeding using superselective embolization with Onyx is feasible and safe.

Radiofrequency ablation for single lung tumours not suitable for surgery: seven years' experience.

PURPOSE: This study was done to review recurrence patterns in patients with lung cancer (primary or secondary) treated with percutaneous image-guided radiofrequency (RF) ablation. MATERIALS AND METHODS: From January 2003 to August 2010, 32 patients (24 with primary non-small-cell lung cancer and eight with metastases) with single lung cancer were treated with RF ablation. Post-treatment imaging results were available for each patient. Follow-up was performed using computed tomography (CT) scans at 1, 3, 6, 12, 18 and 24 months after the procedure and annually thereafter. Patterns of recurrence were classified as local, intrapulmonary, nodal, mixed and distant. We evaluated overall survival after RF ablation and the factors associated with recurrence. RESULTS: Seventeen (53.1%) patients showed no evidence of recurrence at follow-up imaging (range 12-72 months; mean, 32.5 months). Recurrence was seen in 15 (46.9 %) patients (range 6-36 months; mean 14.8 months). Local recurrence (40%) after RF ablation was the most frequent. Median disease-free survival was 20 months. Sex, tumour location, tumour size and tumour stage were not associated with a risk of recurrence. Patient age was related to the risk of recurrence (p<0.05). CONCLUSIONS: Local recurrence is the most common pattern in our series. A more aggressive initial RF ablation might offer improvement in outcomes, but this hypothesis needs to be confirmed by larger studies involving a larger number of patients.

Microorganisms in dry polar snow are involved in the exchanges of reactive nitrogen species with the atmosphere.

The snowpack is a complex photochemical reactor that emits a wide variety of reactive molecules to the atmosphere. In particular, the photolysis of nitrate ions, NO(3)(-), produces NO, NO(2), and HONO, which affects the oxidative capacity of the atmosphere. We report measurements in the European High Arctic where we observed for the first time emissions of NO, NO(2), and HONO by the seasonal snowpack in winter, in the complete or near-complete absence of sunlight and in the absence of melting. We also detected unusually high concentrations of nitrite ions, NO(2)(-), in the snow. These results suggest that microbial activity in the snowpack is responsible for the observed emissions. Isotopic analysis of NO(2)(-) and NO(3)(-) in the snow confirm that these ions, at least in part, do not have an atmospheric origin and are most likely produced by the microbial oxidation of NH(4)(+) coming from clay minerals into NO(2)(-) and NO(3)(-). These metabolic pathways also produce NO. Subsequent dark abiotic reactions lead to NO(2) and HONO production. The snow cover is therefore not only an active photochemical reactor but also a biogeochemical reactor active in the cycling of nitrogen and it can affect atmospheric composition all year round.

Hybrid treatment of isolated aortic arch aneurysms.

PURPOSE: This study sought to assess the feasibility and effectiveness of hybrid treatment of isolated aortic arch aneurysms. MATERIALS AND METHODS: Between December 2000 and December 2006, we selected 14 patients affected by 14 isolated aortic arch aneurysms. All patients had involvement of the left subclavian artery, four of the innominate artery and four of the left carotid artery. All patients underwent intentional exclusion of the left subclavian artery and placement of a straight graft; four patients underwent supra-aortic vessel transposition and four underwent carotid-carotid bypass in one case combined with carotid-subclavian bypass. The procedures were planned with multislice computed tomography (MSCT), in some cases associated with virtual endoscopy. The follow-up was performed with MSCT angiography at 1, 3, 6 and 12 months and yearly thereafter. RESULTS: Immediate technical success was achieved in 100% of cases. There were four ischaemic attacks (three transient ischaemic attacks and one stroke). During follow-up (range 12-48, average 21 months), we observed two type-I endoleaks that were treated by endograft extension, in one case associated with supra-aortic vessel transposition, and two type-II endoleaks that were treated with embolisation. CONCLUSIONS: Hybrid treatment for aortic arch aneurysms is feasible and provides good short-term results, although it requires accurate planning. Further studies are needed to verify the long-term results.

Image-guided percutaneous treatment of abdominal-pelvic abscesses: a 5-year experience.

PURPOSE: This study was undertaken to evaluate the efficacy of image-guided percutaneous drainage in treating abdominal and pelvic abscesses. MATERIALS AND METHODS: From August 2001 to August 2006, 95 patients (49 men and 46 women; mean age 61 years, range 25-92) with 107 abscesses underwent image-guided percutaneous drainage. Thirty-one abscesses were retroperitoneal (9 peripancreatic, 17 perirenal, 5 pararenal), 37 intraperitoneal (2 in communication with the small bowel), 8 intrahepatic (2 in communication with the extrahepatic biliary system and 2 with the intrahepatic biliary system), 4 perisplenic and 27 pelvic (4 in communication with the large bowel). Seventy-one of 107 procedures were performed with ultrasonographic (US) guidance and 36/107 with computed tomography (CT) guidance. All procedures were carried out with 8-to 14-Fr pigtail drainage catheters. RESULTS: Immediate technical success was achieved in 107/107 fluid collections. No major complications occurred. In 98/107 abscesses, we obtained progressive shrinkage of the collection (>50%) with consequent clinical success. In 9/107 cases, percutaneous drainage was unable to resolve the fluid collection. There were 12 cases of catheter displacement and six of obstruction. CONCLUSIONS: Percutaneous drainage is feasible and effective in treating abdominal and pelvic abscesses. It may be considered both as a preparatory step for surgery and a valuable alternative to open surgery. Failure of the procedure does not, however, preclude a subsequent surgical operation.

Indications for the use of the Amplatzer vascular plug in interventional radiology.

PURPOSE: This study was undertaken to assess the indications and effectiveness of the Amplatzer vascular plug (AVP) system in interventional radiology. MATERIALS AND METHODS: Over the past year, we selected 12 patients (seven men and five women; mean age 65.8 years, range 45-82) for the occlusion of five internal iliac arteries (in three aortoiliac aneurysms, one internal iliac aneurysm and one isolated common iliac artery aneurysm), two common iliac arteries (in two ruptured abdominal aortic aneurysms), two subclavian arteries (in aortic arch aneurysms) and three splenic artery aneurysms. We used 15 AVPs (splenic artery aneurysms were excluded, with one AVP in the feeding vessel and one in the draining vessel). RESULTS: We achieved immediate technical success in 12/12 cases. No rupture or dissection of the treated arteries occurred. During the follow-up (mean 4.6 months, range 3-6) computed tomography (CT) angiography and/or contrast-enhanced ultrasound demonstrated complete artery occlusion and aneurysm exclusion. CONCLUSIONS: Ease and speed of use combined with precise, controlled delivery justify the growing use of the AVP in interventional radiology. No doubt, the system's versatility will extend its indications, and larger studies with longer follow-up periods will validate the results achieved so far.

Imaging-guided percutaneous radiofrequency ablation of adrenal metastases: preliminary results at a single institution with a single device.

The aim of this study was to show the feasibility, safety, imaging appearance, and short-term efficacy of image-guided percutaneous radiofrequency ablation (RFA) of adrenal metastases (AM). Seven imaging-guided percutaneous RFA treatments were performed in six patients (two men and four women; mean age, 67.2 years; range, 55-74 years) with six AM who were referred to our institution from 2003 to 2006. One patient was treated twice for recurrence after first treatment. The average diameter of the treated AM was 29 mm (range, 15-40 mm). In all patients, the diagnosis was obtained with CT current protocols in use at our institution and confirmed by pathology with an image-guided biopsy. No major complications occurred. In one patient shortly after initiation of the procedure, severe hypertension was noted; another patient developed post-RFA syndrome. In five of six lesions, there was no residual enhancement of the treated tumor. In one patient CT examination showed areas of residual enhancement of the tumor after treatment. Our preliminary results suggest that imaging-guided percutaneous RFA is effective for local control of AM, without major complications and with a low morbidity rate related to the procedure. Long-term follow-up will need to be performed and appropriate patient selection criteria will need to be determined in future randomized trials.

Post-radiofrequency ablation syndrome after percutaneous radiofrequency of abdominal tumours: one centre experience and review of published works.

The aim of this study was to evaluate prospectively post-radiofrequency ablation (RFA) syndrome and to determine its effect on the quality of life in the 15 days after percutaneous RFA treatment. We carried out an internal review board-approved prospective study of the delayed symptoms that occurred after 71 consecutive RFA sessions in 53 patients (12 women and 41 men; age range 45-83 years; mean age 71.6 years) with 45 primary liver tumours, 34 liver metastases, 3 renal cell carcinoma (RCC), 2 residual lesions from RCC after nephrectomy and 1 pancreatic metastases from RCC. Postablation symptoms occurred in 17 of 53 (32%) patients. Six of 17 patients developed low-grade fever (from 37.5 to 38.5 degrees C). Other symptoms included delayed pain (9/17), nausea (7/17), vomiting (3/17), malaise (3/17) and myalgia (1). Postablation syndrome is a common phenomenon after RFA of solid abdominal tumours. Not only in our study but also in the previous ones the occurrence is observed in approximately one-third patients. Patients should be informed that these symptoms are self-limiting after RFA and most patients should be able to resume near-complete preprocedural levels of activity within 10 days after the procedure.

Esophageal motor function in primary Sjögren's syndrome: correlation with dysphagia and xerostomia.

The incidence of dysphagia in patients with primary Sjogren's syndrome (pSS) has been underestimated and all too often ascribed to xerostomia, without considering the possible presence of esophageal motor abnormalities affecting other nonscleroderma connective tissue diseases. Esophageal and salivary functions were prospectively evaluated in 27 females who met the four criteria proposed by Fox for the diagnosis of pSS, using esophageal manometry after wet swallows and Saxon's test, respectively. Dysphagia was graded using a standard symptoms questionnaire and results were compared with those obtained in a group of 21 healthy controls. Seven patients with pSS (26%) had no swallowing discomfort, 2 (7.4%) had mild dysphagia, 7 (26%) had moderate dysphagia, and 11 (40.6%) had severe dysphagia. Saxon's test revealed an overall decrease in the salivary flow rate compared to controls, with no difference between patients with or without dysphagia. Esophageal manometry demonstrated the absence of any lower or upper esophageal sphincter function abnormalities in all patients. In the patients with pSS as a whole, manometric study of the esophageal body showed a motor pattern comparable with that of controls, with no difference between patients with and without dysphagia. Defective peristalsis, ie, the presence of simultaneous contractions in more than 30% of wet swallows was detected, however, in the distal tract of the esophagus of six patients (22.2%) and in the proximal tract of three (11.1%). All these patients had severe dysphagia and the modified Saxon's test revealed a salivary secretion comparable with that of patients with a normal peristalsis. Dysphagia is a very common complaint in patients with pSS and does not seem to correlate with xerostomia, which is a constant and typical finding of the disease. About one third of patients with pSS have an abnormal esophageal peristalsis that is responsible for severe dysphagia, whereas decreased salivary outflow exacerbates the swallowing discomfort. This has to be taken into account and justifies the routine use of esophageal manometry in patients with pSS. The cause of dysphagia in pSS patients without peristaltic disorders of the esophagus has to be investigated.

Juvenile onset of primary Sjögren's syndrome: report of 10 cases.

OBJECTIVE: Ten new cases with primary Sjögren's syndrome (pSS) whose disease began before age 16 are described. Special attention is paid both to the follow-up and treatment of this condition. METHODS: Cases with juvenile pSS were retrospectively identified from our series of 180 pSS patients. Ocular, salivary, and extraglandular manifestations as well as a full laboratory evaluation including HLA-DR typing were retrieved. RESULTS: A disease prevalence of 5.5% (10 cases, 8 female and 2 male) was found in our series. The mean age at onset was 11.0 years, but the disease started at the age of 4 in 2 patients. At onset, parotid swelling was found in 6 cases and extraglandular manifestations in 3. Throughout the follow-up period (mean 48.6 months from the time of diagnosis), the clinical picture was similar to that of pSS in adults, but oral involvement was generally milder. Extraglandular manifestations were always present but never severe. Pertinent laboratory abnormalities (e.g. rheumatoid factor, polyclonal hypergammaglobulinemia, leukopenia, increased ESR, ANA and anti-SSA/SSB antibodies) were found in all patients. Specifically, ANA and anti-SSA were always positive. Moreover, in our cases histocompatibility antigens HLA-DR3 and DR 52 were closely associated with the disease. Clinical outcome was difficult to predict; however, no serious complications have been observed so far. We obtained good results with low-dose steroids and/or hydroxychloroquine, especially with regard to the extraglandular manifestations and laboratory abnormalities. CONCLUSION: We confirm that juvenile pSS is not a rare condition. It closely resembles pSS in adults except for the extremely high prevalence of recurrent parotitis and immunological findings.

[Diagnostic value of labial salivary biopsy in Sjogren's syndrome: report of 182 cases]. / Valore diagnostico della biopsia delle ghiandole salivari minori nella sindrome di Sjögren (Studio su 182 casi).

Various sets of criteria have been suggested in order to establish a diagnosis of Sjögren's syndrome (SS) in as much as evaluation of the salivary component is highly controversial. Our study was aimed at investigating both sensitivity and specificity of labial salivary gland biopsy (LSGB), as well as at comparing this method with other diagnostic procedures commonly employed in SS. LSGB was performed in 182 patients (174 female and 8 male, mean age 51.2) with xerostomia, dry eyes, parotid swelling and/or serological abnormalities such as positive rheumatoid factors, antinuclear antibodies, leukopenia and hypergammaglobulinemia. Diagnosis of SS was made according to the criteria recently proposed by Vitali et al. (1993). Severity of histologic changes was graded according to the Chisholm and Mason scoring system. Bioptic samples were considered abnormal when at least one focus of mononuclear cells/4mm2 was observed. The following parameters were also assessed in each patient: questionnaire of symptoms, Saxon test, sialography, salivary dynamic scintiscan, Schirmer-I-test, rose Bengal score, ANA, anti-SSA/SSB antibodies and rheumatoid factors. According to the above diagnostic criteria, 108 out of 182 patients had SS, 90 primary and 18 secondary. For 74 there were not enough data for a definite diagnosis of SS. In 9 cases (4 with and 5 without SS) LSGB was excluded because no glandular tissue was found in the specimens. Among the remaining 173, Grades 3 or 4 were found in 74 patients (71.2%) with SS and only in 1 case (1.4%) without SS. LSGB showed a very high specificity (98.6%) and a rather good sensitivity (72.5%). However, biopsy was crucial for diagnosis in only 11 cases (14.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Neutropenia in glycogenesis I B]. / Neutropenia nella glicogenosi IB.

Type IB Glycogen storage disease (GSD) is a new variant of type I Glycogen storage disease. It is characterized by same clinical findings: hepatomegaly, fasting hypoglycemia, hyperlipidemia, hyperuricemia, lactic acidosis, renal enlargement, short stature; but it distinguish for normal glucose-6-phosphatase hepatic activity in vitro. The involvement is in G-6-P transport system. Recently has been described in some patients with GSD IB, neutropenia and defective neutrophil mobility. In this report the authors described two family cases of GDS IB that one characterized by severe neutropenia.

[Lawrence Moon Biedl Bardet, a polymorphic syndrome]. / Laurence Moon Biedl Bardet, una sindrome polimorfa.

The Laurence Moon Biedl Bardet syndrome is a polymorphous disease whose pathogenesis is still obscure. It is characterize by obesity, oligophrenia, polidactylia, retinitis pigmentosa, hipogonadism, but often there are various others symptoms. AA describe two cases. After a short explanation of de main features of this disease, they dwell upon the study of clinical objective symtomatology and upon instrumental and laboratory parameters regarding hormonal, metabolic and functional order of various organs and apparatuses. Both cases present all classic symptoms of this disease. In the first case we have noticed a deficit in LH and FSH, besides we have also noticed an asymmetry of the lateral ventricles of the brain prevalently on the right and a small increase in 17-KS and 17-OH-KS urinary. On the contrary in the second case we have noticed an EEG of epileptic type.