Distinct microRNA signatures in human lymphocyte subsets and enforcement of the naive state in CD4+ T cells by the microRNA miR-125b.

MicroRNAs are small noncoding RNAs that regulate gene expression post-transcriptionally. Here we applied microRNA profiling to 17 human lymphocyte subsets to identify microRNA signatures that were distinct among various subsets and different from those of mouse lymphocytes. One of the signature microRNAs of naive CD4+ T cells, miR-125b, regulated the expression of genes encoding molecules involved in T cell differentiation, including IFNG, IL2RB, IL10RA and PRDM1. The expression of synthetic miR-125b and lentiviral vectors encoding the precursor to miR-125b in naive lymphocytes inhibited differentiation to effector cells. Our data provide an 'atlas' of microRNA expression in human lymphocytes, define subset-specific signatures and their target genes and indicate that the naive state of T cells is enforced by microRNA.

Psychomotor Development in Cri du Chat Syndrome: Comparison in Two Italian Cohorts with Different Rehabilitation Methods.

The Cri du Chat syndrome (CdC) is a rare genetic disorder caused by variable size deletions of the short arm of chromosome 5 (5p-). It is well known that home-reared patients show better performances as compared to institutionalised cases, and it was reported that continuous educational intervention can ameliorate their performances. To assess the efficacy of educational intervention and to develop new CdC oriented programs of rehabilitation, we compare the results obtained for many developmental skills in two groups of CdC patients undergoing two different rehabilitation programs. Using data on the development of a group of CdC patients obtained by validated Italian translation for the Denver Developmental Screening Test II, we compared a group of 13 patients undergoing an educational program developed for CdC patients, the Mayer Project (MP), with a second group of 15 cases in whom caring was not specifically oriented. A positive impact of the MP was reported by parents, observing an improvement in social skills obtained, even if no significant differences were observed when the items of the Denver Test are studied. The need for personalized care in CdC patients and the choice of different methods to compare the results are also discussed.

Drug attitude in adolescents: a key factor for a comprehensive assessment.

OBJECTIVE: Very few studies have evaluated the subjective experience (SE) in children and adolescents treated with antipsychotics. The present study aimed to evaluate the SE of antipsychotics in adolescents diagnosed with different psychiatric conditions and to identify explanatory variables of adolescents' SE and compliance with treatment. METHODS: The Drug Attitude Inventory (DAI) was used to evaluate SE in 67 adolescents in 2 different countries (Italy and United Kingdom). Compliance was measured using a Likert scale completed by both patients and parents. To evaluate other parameters correlated to the SE, the following scales were administered: Clinical Global Impression Scale, Children's Global Assessment Scale, Extrapyramidal Symptoms Rating Scale, Barnes Akathisia Rating Scale, and EuroQoL (for quality of life). Multiple and logistic regression analyses were applied. RESULTS: No significant difference in drug attitude was found between psychotic and nonpsychotic patients. Our results showed a highly significant association between DAI and compliance (Spearman index, 0.33; P = 0.005); for all other variables, DAI associated significantly only with quality of life (r = 0.25; P = 0.03). The multivariable analysis confirmed the presence of a strong association between compliance and DAI (P = <0.001). In our sample, drug attitude was the only variable found to be correlated with the compliance, whereas extrapyramidal adverse effects showed an only marginally significant association. CONCLUSIONS: Our observations provide confirmation, also in adolescents, that drug attitude is strongly correlated with treatment compliance and underline the need in clinical assessments to always consider the patient's viewpoint.

Accuracy of a novel risk index combining degree of stenosis of the carotid artery and plaque surface echogenicity.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the accuracy of a risk index in symptomatic or asymptomatic carotid stenoses. METHODS: Consecutive patients presenting 50% to 99% carotid stenoses were included. A semiautomated gray scale-based color mapping (red, yellow, and green) of the whole plaque and of its surface was achieved. Surface was defined as the region located between the lumen (Level 0) and, respectively, 0.5, 1, 1.5, and 2 mm. Risk index was based on a combination of degree of stenosis and the proportion of the red color (reflecting low echogenicity) on the surface or on the whole plaque. RESULTS: There were 67 (36%) symptomatic and 117 (64%) asymptomatic carotid stenoses. Risk index values were higher among symptomatic stenoses (0.46 mean versus 0.29; P<0.0001); on receiver operating characteristic curves, risk index presented a stronger predictive power compared with degree of stenosis or surface echogenicity alone. Also, in a regression model including age, gender, degree of stenosis, surface echogenicity, gray median scale of the whole plaque, and risk index, risk index measured within the surface region located at 0.5 mm from the lumen was the only parameter significantly associated with the presence of symptoms (OR, 4.89; 95% CI, 2.7-8.7; P=0.0000002). The best criterion to differentiate between symptomatic and asymptomatic stenoses was a risk index value >0.36 (sensitivity and specificity of 78% and 65%, respectively). CONCLUSIONS: Risk index was significantly higher in the presence of symptoms and could therefore be a valuable tool to assess the clinical risk of a carotid plaque.

Systemic exposure to rifampicin in patients with tuberculosis and advanced HIV disease during highly active antiretroviral therapy in Burkina Faso.

OBJECTIVES: Low plasma concentrations of rifampicin, an essential antituberculosis drug, have been reported particularly among HIV co-infected persons. In a prospective, longitudinal study we measured rifampicin systemic exposure at different timepoints during highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: From May 2006 to April 2007, 16 tuberculosis (TB)/HIV co-infected patients were enrolled in Ouagadougou, Burkina Faso. All patients received fixed dose combinations of rifampicin, isoniazid, pyrazinamide and ethambutol under direct observation and HAART, consisting of a fixed dose combination of stavudine, lamivudine and nevirapine. Rifampicin concentrations during the dosing interval were determined by HPLC at three different timepoints: (i) after 2 weeks of TB therapy and before starting HIV therapy (T0); (ii) after 4 weeks of combined therapy (T1); and (iii) after 10 weeks of combined therapy (T2). RESULTS: The median values of the area under the curve (AUC(0-24)) of rifampicin increased by 39% at T1 (15.69 µg ·â€Šh/mL; P = 0.01) and by 83% at T2 (20.65 µg ·â€Šh/mL; P = 0.001) compared with T0 (11.28 µg ·â€Šh/mL). Similar variations were observed for the median C(max) at T0 (2.24 µg/mL) compared with T2 (2.83 µg/mL; P = 0.003). However, none of the subjects had C(max) levels >8 µg/mL at either T0 or T2. CONCLUSIONS: Rifampicin systemic exposure increased during combined TB and HIV therapy, possibly due to increased drug absorption or decreased oral clearance, but remained invariably low in this population. Studies to define the C(max) rifampicin concentrations, which are associated with a significantly increased risk of treatment failure, are urgently warranted.

[An update on several indicators of the quality of data flow in a cancer registry in Vercelli (Piedmont, Italy)]. / L'incidenza oncologica nell'ASL VC di Vercelli dal 2002 al 2009: aggiornamento indicatori di qualità del flusso informativo.

The first estimates of cancer incidence in the city of Vercelli in Piedmont (Italy) are now available for the years 2002 to 2005 and preliminary data are also available up to 2009. With respect to previously published results, the cancer database has been integrated with information from additional data sources to ensure that it will become, in the near future, a sound basis of information upon which to build an accredited cancer registry. An evaluation was therefore performed of two indicators of the quality of data flow: the proportion of cases with histological confirmation of diagnosis and cancer mortality to incidence (M/I) ratios. Both show an improvement with respect to 2005 but need to be significantly improved to reach the levels of excellence and accuracy that a registry must necessarily possess. Local health authorities will need to ensure staff availability and facilitate access to key data sources to fully evaluate cancer epidemiology in the area.

Long-term effects of high-efficiency on-line haemodiafiltration on uraemic toxicity. A multicentre prospective randomized study.

BACKGROUND: Haemodiafiltration (HDF) may improve survival of chronic dialysis patients. This prospective, multicentre randomized cross-over study evaluated the effects of long-term on-line HDF on the levels of solutes of different molecular weight markers or causative agents of the most common metabolic derangements in uraemia. METHODS: Sixty-nine patients from eight Italian centres were randomly assigned to two 6-month treatment sequences: A-B and B-A [A, low-flux haemodialysis (HD) and B, on-line HDF]. Comparative evaluation of basal levels of small, medium-sized and protein-bound solutes at the end of the two treatment periods and analysis of parameters dependence during the interventions were performed. RESULTS: On-line HDF showed greater efficiency than low-flux HD in removing small solutes (eKt/Vurea 1.60 ± 0.31 versus 1.44 ± 0.26, P < 0.0001) and in reducing basal levels of beta2-microglobulin (22.2 ± 7.8 versus 33.5 ± 11.8 mg/L, P < 0.0001), total homocysteine (15.4 ± 5.0 versus 18.7 ± 8.2 µmol/L, P = 0 .003), phosphate (4.6 ± 1.3 versus 5.0 ± 1.4 mg/dL, P = 0.008) and, remarkably, of intact parathyroid hormone (202 ± 154 versus 228 ± 176 pg/mL, P = 0.03). Moreover, in on-line HDF, lower levels of C-reactive protein (5.5 ± 5.5 versus 6.7 ± 6.1 mg/L, P = 0.03) and triglycerides (148 ± 77 versus 167 ± 87 mg/dL, P = 0.008) and increased HDL cholesterol (49.2 ± 12.7 versus 44.7 ± 12.4 mg/dL, P = <0.0001) were observed. The asymmetric dimethylarginine level was not significantly affected (0.97 ± 0.4 versus 0.84 ± 0.37 µmol/L). Erythropoietin and phosphate binders' doses could be reduced. CONCLUSIONS: On-line high-efficiency HDF resulted in enhanced removal and lower basal levels of small, medium-sized and protein-bound solutes, which are markers or causative agents of uraemic pathologies, mainly inflammation, secondary hyperparathyroidism and dyslipidaemia. This may contribute to reducing uraemic complications and possibly to improving patient survival.

[Cancer mortality in a local health district of Vercelli (Italy) 2000-2009]. / Andamento della mortalità oncologica nell'Asl Vc di Vercelli. Estensione database al 2006-2009 e analisi decennio 2000-2009.

Cancer mortality data for 2000-2009 in the local health district of Vercelli (northern Italy) were analysed. Overall, standard mortality rates show excess mortality rates in men for colon and rectal cancers, central nervous system cancers, as well as esophageal, laryngeal, renal, lung, skin (non melanoma) and skeletal system cancers. For women, excess mortality rates were found for skin (non melanoma), leukemias, nervous system cancers, lymphomas and skeletal system cancers. Mortality data for the years 2006-2009 were compared to data for 2000-2005. Results show an increased mortality risk for mesothelioma in the period 2006-2009 with respect to the period 2000-2005. On the other hand decreased mortality risks were found for nervous system tumours and leukemia, even though current standard mortality rates remain in excess. In light of these findings, it is advisable to monitor the phenomenon in the coming years and to conduct studies to identify possible risk factors.

Seasonal fluctuations in problem behaviors among young adults with autism and intellectual disability.

BACKGROUND: Acute behavioral alterations have been frequently reported in patients with autism. However, the question as to whether behavioral problems undergo seasonal variations in autism remains to be addressed. MATERIAL/METHODS: In a prospective observational study over 29 months, problem behaviors amongst 23 young adults with autism and intellectual disability living in a farm community center were assessed. Behavioral problems were recorded daily using the Rossago Behavioral Checklist. Data were collected on clinical characteristics, drug usage, changes in staff composition, daily schedule, rehabilitative activities, and food administration. RESULTS: Problem behaviors showed significant seasonal fluctuations. The frequency of problem behaviors showed a maximum in mid-April and a minimum in mid-October (mean difference: 1.24 behaviors). CONCLUSIONS: Taken together, these data suggest the occurrence of significant seasonal fluctuations in problem behaviors amongst young adults with autism and intellectual disability. Further studies are needed to shed more light on the mechanisms underlying these fluctuations.

Differences in biofilm formation and aggregative adherence between beta-lactam susceptible and beta-lactamases producing P. mirabilis clinical isolates.

Biofilm formation of multidrug resistant (MDR) extended-spectrum beta-lactamase (ESbetaL) producing Proteus mirabilis isolates from a long-term care and rehabilitation facility (LTCRF) in Northern Italy was evaluated. A total of 10 strains, 4/10 producing the acquired AmpC beta-lactamase CMY-16, 3/10 producing the ESbetaL TEM-92 and the remaining negative for the presence of beta-lactamase genes, were studied using standard adherence assays on titer plates. Tests were performed in three different media, including Luria Bertani (LB), LB diluted and urine. Three representative strains were also tested for biofilm production in microtiter in presence of beta-lactam sub-MIC concentrations. The same isolates were screened for aggregative adherence onto monkey kidney cells (LLC-MK2). All strains studied were capable of biofilm formation, though at different levels. The beta-lactamase positive strains were statistically better significant in biofilm formation than negative ones regardless of growth medium. Cellular adherence assays showed a preferential ability of all isolates, regardless of beta-lactamase production, to adhere to inert surfaces rather than to cells. Although the results did not fully support a direct correlation between beta-lactamase production and biofilm formation, both mechanisms can greatly contribute to bacterial persistence in the urinary tract.

Mixed hemodiafiltration reduces erythropoiesis stimulating agents requirement in dialysis patients: a prospective randomized study.

BACKGROUND: Improved responsiveness to erythropoiesis stimulating agents (ESAs) in patients on on-line post-dilution hemodiafiltration (Post-HDF) compared with conventional hemodialysis (HD) was reported by some authors but challenged by others. This prospective, cross-over randomized study tested the hypothesis that an alternative infusion modality of HDF, mixed-dilution HDF (Mixed HDF), could further reduce ESAs requirement in dialysis patients compared to the traditional Post-HDF. METHODS: One-hundred-twenty prevalent patients from 6 Dialysis Centers were randomly assigned to two six-months treatment sequences: A-B and B-A (A, Mixed HDF; B, Post-HDF). Primary outcome was comparative evaluation of ESA (darbepoetin alfa) requirement and ESA resistance. Treatments efficiency, iron and vitamins status, inflammation and nutrition parameters were monitored. RESULTS: In sequence A, darbepoetin requirement decreased during Mixed HDF from 29.5 to 23.7 µg/month and increased significantly during Post-HDF (32.3 µg/month at 6th month) while, in sequence B, it increased during Post-HDF from 38.2 to 43.7 µg/month and decreased during Mixed HDF (23.9 µg/month at 6th month). Overall, EPO doses at 6 months on Mixed and Post-HDF were 23.8 and 38.4 µg/month, respectively, P < 0.01. A multiple linear model confirmed that Mixed HDF vs Post-HDF reduced significantly ESA requirement and ESA resistance (P < 0.0001), by a mean of 29% (CI 23-35%) in the last three months of the observation periods. CONCLUSIONS: Mixed HDF decreased darbepoetin-alfa requirement in dialysis patients. This might help preventing the untoward side effects of high ESA doses, besides having a remarkable economic impact. Additional evidence is needed to confirm this potential benefit of Mixed-HDF.

Dietary intakes in infertile women a pilot study.

BACKGROUND: The reproductive axis is closely linked to nutritional status. The purpose of this study was to compare the nutritional status in two groups of young infertile women, without clinically overt eating disorders: hypothalamic amenorrhea (HA) and polycystic ovary syndrome (PCOS). METHODS: Eighteen young infertile women (10 HA, 8 PCOS) attending an outpatient gynecological endocrinology unit, underwent evaluation of anthropometry, body composition, dietary intakes by means of a food frequency questionnaire (FFQ) and a seven-day food diary (7DD), and psychological characteristics by means of EDI2 and SCL90 tests. RESULTS: HA women had lower BMI and body fat compared to PCOS women. Habitual intake derived from FFQs showed a similar macronutrient distribution between groups (about 16% protein, 33% fat, 52% carbohydrates). The psychometric profiles of the two groups did not differ significantly. The underreporting of dietary intakes (measured as habitual energy intake by FFQs/basal metabolic rate) was found to be negatively correlated with the interpersonal sensitivity SCL-90 subscale scores (r = -0.54, p = 0.02). CONCLUSION: Our study identified differences in body composition but not in dietary habits between HA and PCOS infertile women. We documented, for the first time, a relationship between the accuracy of dietary surveys and the psychological characteristics of subjects with anovulation. This finding suggests that it may be important to be aware of the psychological terrain when planning a dietary survey in infertile women.

[Estimating the incidence of cancer in the VC Local Health Authority in Vercelli (Italy) from 2002 to 2005]. / Stime d'incidenza oncologica nell'Asl Vc di Vercelli dal 2002 al 2005.

The aim of this study was to describe the epidemiology of tumours in a geographical area in Italy devoid of a tumour registry. A descriptive study was conducted in the territory of the VC local health authority. To estimate incidence, hospital discharge forms were analysed together with data from pathology archives. The standardized incidence rate (SIR) was calculated by using age specific rates in the VC local health authority in the years 2002-2005 and the tumour incidence in the city of Turin as the standard population. As regards low mortality tumours, an excess of bladder cancers (SIR=1,2; 1,1-1,3) and melanomas (SIR=1,3; 1,1-1,6) were found in males and of thyroid cancer (SIR=1,9; 1,6-2,2) and non-Hodgkin lymphomas (SIR=1,4; 1,2-1,6) in females. In addition, an excess of rectal and colon cancers, and leukemia were observed in both genders and of central nervous system tumours in women. This preliminary study may be considered as a basis for the creation of a tumour registry which would necessarily need to integrate additional sources of information. In any case the results of this study have identified certain peculiarities regarding the epidemiology of tumours in this area, which should be further studied in terms of a Public Health problem.

[Epidemiology of tumour mortality from 2000 to 2005 in the province of Vercelli (Italy)]. / La mortalità per tumore in provincia di Vercelli dal 2000 al 2005: considerazioni territoriali ed epidemiologiche.

The main aim of this study was to assess the burden of cancer disease in residents of Vercelli (northern Italy), by analysing mortality data and hospital discharge forms. This was done in order to verify whether, as widely suspected among the city's population, an increased risk of cancer exists in the area, due to the large number of existing agricultural and industrial activities. Tumour mortality rates were compared with mortality data from the tumour registries of the province of Biella and of the city of Turin to identify a possible excess number of cases in Vercelli.An increased mortality rate was observed with respect to reference values (mortality registry of the city of Turin) for several tumours; more specifically results revealed a significantly increased mortality rate due to colorectal tumours, leukemias and nervous system tumours in both genders. Excess mortality was detected in males but not in females for esophageal cancer, non melanoma skin cancers, pancreatic, laryngeal, prostatic, renal and bone cancers. Conversely, in females, the standard mortality ratios (SMR) were found to be statistically significant for renal and laryngeal cancers and for Hodgkin's lymphoma.

Behavioral effects of omega-3 fatty acid supplementation in young adults with severe autism: an open label study.

BACKGROUND: Pilot findings seem to suggest a potential beneficial effect of omega-3 fatty acid (FA) supplementation on behavioral alterations in children with autism. However, data on the potential benefits of omega-3 supplements in young adults with severe autism are lacking. In the present study, we sought to explore this issue in an open label study. METHODS: Nineteen young adults with severe autism (CARS >40), aged 18-40 years, received two fish oil capsules per day [0.93 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plus 5 mg of vitamin E to avoid lipid peroxidation] for 6 weeks. Subjects were assessed with an ad hoc caregiver questionnaire, the Rossago Behavioral Checklist, for the assessment of behavioral anomalies. RESULTS: No significant improvements were observed with regard to the severity and frequency of problematic behaviors either during the active treatment period or during the post-treatment 6-week observation period. Moreover, no effect on the number of episodes and severity of behavior aberrations was observed. CONCLUSIONS: Our negative findings do not point toward a major effect of omega-3 FA supplementation on behavioral abnormalities in adults with severe autism. Further studies on larger sample sizes are warranted to shed more light on this important issue.

Pharmacogenomic Approach to Selecting Antiplatelet Therapy in Patients With Acute Coronary Syndromes: The PHARMCLO Trial.

BACKGROUND: Although clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), its efficacy is hampered by interpatient response variability caused by genetic polymorphisms associated with clopidogrel's metabolism. OBJECTIVES: The goal of this study was to evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel, or ticagrelor) on the basis of a patient's genetic and clinical characteristics leads to better clinical outcomes compared with the standard of care, which bases the selection on clinical characteristics alone. METHODS: Patients hospitalized for ACS were randomly assigned to standard of care or the pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, and CYP2C19*17 using an ST Q3 system that provides data within 70 min at each patient's bedside. The patients were followed up for 12 ± 1 month for the primary composite endpoint of cardiovascular death and the first occurrence of nonfatal myocardial infarction, nonfatal stroke, and major bleeding defined according to Bleeding Academic Research Consortium type 3 to 5 criteria. RESULTS: After enrolling 888 patients, the study was prematurely stopped. Clopidogrel was used more frequently in the standard-of-care arm (50.7% vs. 43.3%), ticagrelor in the pharmacogenomic arm (42.6% vs. 32.7%; p = 0.02), and prasugrel was equally used in both arms. The primary endpoint occurred in 71 patients (15.9%) in the pharmacogenomic arm and in 114 (25.9%) in the standard-of-care arm (hazard ratio: 0.58; 95% confidence interval: 0.43 to 0.78; p < 0.001). CONCLUSIONS: A personalized approach to selecting antiplatelet therapy for patients with ACS may reduce ischemic and bleeding events. (Pharmacogenetics of Clopidogrel in Patients With Acute Coronary Syndromes [PHARMCLO]; NCT03347435).

Correlation of cerebrovascular symptoms and microembolic signals with the stratified gray-scale median analysis and color mapping of the carotid plaque.

BACKGROUND AND PURPOSE: To determine whether a stratified gray-scale median (GSM) analysis of the carotid plaque combined with color mapping correlated better with the presence of neurological symptoms and microembolic signals (MES) than a whole plaque measurement. METHODS: A total of 131 patients presenting 167 carotid stenoses between 30% and 99% were analyzed by ultrasound. Emboli detection was performed by transcranial Doppler. For each plaque, the GSM values at depth 0 mm (surface) and at one third (30) and one half (50) of the plaque thickness were compared with the values obtained for the whole plaque. The plaque pixels were mapped into 3 colors: red, yellow and green, depending on their GSM value. RESULTS: Mean GSM values were lower among symptomatic plaques, but a statistically significant difference between values of the whole plaque and those of the surface was obtained only for MES+ stenoses (P<0.01). In a proportional odds logistic regression model based on 4 subgroups with an increasing clinical risk (MES-/symptoms-; MES-/symptoms+; MES+/symptoms-; +; MES+/symptoms+), low mean GSM values and the predominant red color at the surface were independent factors associated with the presence of symptoms or MES (P<0.0005). Furthermore, compared with a whole plaque measurement, analysis of the surface values predicted systematically with a greater sensitivity and specificity (receiver operating characteristic curves) each one of these 4 subgroups. CONCLUSIONS: Low mean GSM values and predominance of the red color at the surface correlated with most of the symptomatic or MES+ stenoses. This combined approach should be further investigated in a longitudinal study.

Intravenous versus combined (intravenous and intra-arterial) thrombolysis in acute ischemic stroke: a transcranial color-coded duplex sonography--guided pilot study.

BACKGROUND AND PURPOSE: Determine feasibility and safety of intravenous (IV) versus combined (IV-IA [intra-arterial]) thrombolysis guided by transcranial color-coded duplex sonography (TCCD). METHODS: Thirty-three patients eligible for IV thrombolysis, within 3 hours of onset of symptoms, with occlusion in middle cerebral artery territory (TCCD monitoring, thrombolysis in brain ischemia [TIBI] flow grade [0-3]), underwent IV thrombolysis (tissue plasminogen activator, 0.9 mg/kg). In case of recanalization (modification of TIBI score > or =1) after 30 minutes IV thrombolysis was continued over 1 hour; otherwise, it was discontinued, with subsequent IA thrombolysis. Recanalization was determined by TIBI (TCCD) and angiographically by thrombolysis in myocardial infarction (TIMI) flow grades. Clinical outcome measures were assessed at baseline, 24 hours (NIHSS) and 3 months (modified Rankin Scale). RESULTS: In the IV group, 10/17 patients (59%) with complete or partial recanalization after 30 minutes had a favorable outcome at 3 months (modified Rankin Scale 0 to 2). TIBI flow grades 3 to 5 after 30 minutes of IV thrombolysis predicted a good prognosis compared with TIBI grades 1 to 2 (P<0.05). In the combined IV/IA therapy group (no recanalization after 30 minutes), 9/16 patients (56%) had a favorable outcome at 3 months. One symptomatic intracerebral hemorrhage occurred in each group. CONCLUSIONS: Combined IV-IA versus IV thrombolysis guided by TCCD was feasible and safe. Recanalization after 30 minutes of IV thrombolysis led to a favorable outcome in 59% of the patients, provided TIBI flow grades were of 3 to 5. In the absence of early recanalization during IV thrombolysis, there was clinical benefit to proceed to IA therapy for a significative proportion of patients (56%).

Prognostic validation of the international classification of immunoglobulin M gammopathies: a survival advantage for patients with immunoglobulin M monoclonal gammopathy of undetermined significance?

PURPOSE: To verify the reliability of the new criteria for the diagnosis of IgM gammopathies recently proposed by an international panel of experts (Athens, 2002). EXPERIMENTAL DESIGN: A retrospective series of 698 patients with IgM gammopathy was reviewed paying attention to symptoms, serum IgM concentration, bone marrow infiltration, blood cell count and clinical course. Four clinical entities can be identified: IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), asymptomatic and symptomatic Wandenstrom's macroglobulinemia (A-WM and S-WM, respectively), and IgM-related disorders, although this last was excluded from the study because of the scarcity of patients due to probable selection biases. The observed mortality was studied related to that expected in the general population of comparable age and sex and over an equivalent period of follow-up (standardized mortality ratio, SMR). RESULTS: IgM-MGUS, A-WM, and S-WM shared many clinical aspects but, with respect to the general population, patients with IgM-MGUS had a slight but definite survival advantage, those with A-WM had a mortality rate equivalent to that of the general population, whereas the SMR of patients with S-WM was 5.4. Within A-WM and S-WM the SMR values did not vary significantly in relation to marrow lymphocyte counts or serum IgM concentrations. CONCLUSIONS: Our findings represent a prognostic validation of the applied diagnostic criteria for three of the four identifiable clinical entities and highlight the importance of symptoms over serum IgM concentration and marrow infiltration.

Are car drivers holding a motorcycle licence less responsible for motorcycle--car crash occurrence? A non-parametric approach.

The purpose of this work is to evaluate the effect of a specific motorcycle licence, held by car drivers, in responsibility for motorcycle-car crashes. The data were provided by a multicentric case-control study (MAIDS) regarding the risk of crash and serious injuries of motorcyclists. A non-parametric method, classification and regression tree (CART), was used to accomplish the objective, and then compared to standard unconditional logistic regression. Drivers owning a motorcycle licence turned out to be less responsible for motorcycle-car crashes than drivers who do not have one; both types of analysis are consistent with this result. It is reasonable to assume that car drivers who hold a motorcycle licence have acquired more ability in riding and controlling two wheeled vehicles than drivers without a licence, and this may help them in predicting motorcycles manoeuvres.