Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes

It is uncertain whether patients with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) have a milder disease and should undergo liver biopsy. We reviewed the histological data of 458 Italian patients with NAFLD in whom liver biopsy was indicated by altered liver enzymes (395 cases, 86%), or persistently elevated ferritin or long-lasting severe steatosis (63 cases). Factors associated with nonalcoholic steatohepatitis (NASH) and fibrosis >/= 2 were identified by multivariate analysis. Patients with normal ALT were significantly older, had lower body mass index, fasting triglycerides, insulin resistance according to homeostasis model assessment (HOMA-IR), ALT, and gamma-glutamyltransferase, but a higher prevalence of hypertension. NASH was diagnosed in 59% and 74% of the patients with normal and increased ALT, respectively (P = 0.01). In the overall series of patients, NASH was independently predicted by ALT (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.04-1.19 per 10-IU/mL increase) and diabetes (OR, 1.5; 95% CI, 1.1-2.0). The same variables were selected in patients with increased ALT, whereas in those with normal ALT, HOMA-IR and ALT were independent predictors. Severe fibrosis was independently predicted by serum ferritin (OR, 1.04; 95% CI, 1.001-1.08 per 50-ng/mL increase), ALT (OR, 1.07; 95% CI, 1.02-1.14), and diabetes (OR, 1.8; 95% CI, 1.4-2.3) in the overall series, serum ferritin and diabetes in those with increased ALT, and only HOMA-IR (OR, 1.97; 95% CI, 1.2-3.7) in patients with normal ALT. CONCLUSION: Normal ALT is not a valuable criterion to exclude patients from liver biopsy. Alterations in glucose metabolism and insulin resistance in subjects with normal ALT should also be considered in the selection of NAFLD cases for histological assessment of disease severity and progression.     

Barriers and incentives for Italian paediatricians to become smoking cessation promoters: a GARD-Italy Demonstration Project

BackgroundPaediatricians rarely devote any time to screening and treatment for parental tobacco use. The present project is part of a Global Alliance against Chronic Respiratory Diseases (GARD)-Italy Demonstration Project, aimed to increase the skills of primary care physicians and paediatricians as “promoter of smoking cessation”. The aims of this study were: (I) to identify latent classes of barriers and incentives for smoking cessation counseling among paediatricians using latent class analysis (LCA); (II) to investigate risk factors for inclusion into the identified classes.MethodsIn 2018, 1,500 Italian paediatricians were invited to complete an online survey on passive smoke exposure in children. LCA was used to discover underlying response patterns, and to identify respondent groups with similar attitudes toward passive smoke exposure in children. Multinomial logistic regression helped investigate which explanatory variables influenced inclusion into a class. A P value <0.05 was considered significant.ResultsThe overall response rate was 71% (n=1,071/1,500). Three classes were identified: Class 1 “passive” (n=226, 21.10%); Class 2 “unmotivated” (n=124, 11.58%); and Class 3 “proactive” (n=721, 67.32%). Assuming Class 3 as reference, ever having been a smoker was borderline associated (P=0.052) with increased probability of inclusion into Class 1 (OR =1.43, 95% CI, 1.00–2.06). Having 6–15 or ≥15 years of work experience versus having less than five years was associated with decreased probability of being in the “passive” class (OR =0.46, 95% CI, 0.22–0.96 and OR =0.49, 95% CI, 0.27–0.87, respectively), as was discussing parents’ addiction to alcohol/drugs (OR =0.50, 95% CI, 0.33–0.76).ConclusionsWe identified three profiles among Italian paediatricians related to barriers and incentives for smoking cessation promotion. Tailored educational interventions for paediatricians are required to promote smoking cessation programs.     

A practical definition of minor stroke

It is generally assumed that minor stroke (MS) is an ischemic stroke with a short-term, good functional outcome. However, no clear definition of MS exists. Modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS) are still the most accredited standards, but scores and timing of the assessment are not homogeneous. As suggested by a qualified sample of Italian neurologists, the index parameter chosen in our analysis was mRS at the time of hospital discharge. The database of the SIRIO study (a large observational study of 2,573 patients with stroke admitted in Italian hospitals in 2005) was used to identify an mRS threshold to define MS. Reference was made to outcome markers such as rate of discharge to home, 1-year disability and 1-year mortality. The rate of discharge progressively decreased with increase in mRS, while the rates of 1-year mortality and disability progressively increased. Our proposal is one of defining a stroke “minor” when the rate of discharge to home is above the SIRIO database overall value and the 1-year mortality and disability is below the respective overall values. This definition is consistent with a score ≤2 on the mRS.     

Secreted Wnt Antagonists During Eradication of Cytomegalovirus Infection in Solid Organ Transplant Recipients

We evaluated secreted wingless (Wnt) modulators during cytomegalovirus (CMV) infection in solid organ transplant recipients (SOTr). The major findings were: (i) Plasma levels of Dickkopf‐1 (DKK‐1) were significantly lower in patients with CMV DNAemia above lower level of quantification at baseline. (ii) Receiver operating characteristic analysis indicated that low DKK‐1 and increased secreted frizzled related protein‐3 levels were predictors of poor virological outcomes during follow‐up. Our findings demonstrate an imbalanced pattern of circulating secreted Wnt modulators in SOTr with poor virological outcomes following treatment for CMV disease, and may suggest a role for dysregulated Wnt signaling on viral pathogenesis during CMV infection.     

Pharmacokinetic approach to proglumide long-term activity

In order to explain the long-term therapeutic activity of (+/-)-4-benzamide-N,-di-n-propylglutaramic acid (proglumide, Milid) a pharmacokinetic study was carried out in rats by three administration routes. As a result, experimental data could have been fitted to a tri- or tetra-exponential equation, with terminal half-life of about 24 h. Since human pharmacokinetics was found to be rather similar to that in rats, it can be extrapolated that steady state plasma level of drug during therapeutic dosage regimen should range around 60% of peak level of single administration.     

Anatomical correlates of visual and tactile extinction in humans: a clinical CT scan study.

The anatomical correlates of tactile and visual extinction with double simultaneous stimulation were investigated in a series of 159 patients with right brain damage caused by stroke. Forty six patients showed extinction (22 tactile, 14 visual, 10 tactile and visual). Over 50% of the patients with extinction had deep lesions, which were found in about 25% of the patients with visuospatial neglect not associated with extinction. In the patients with extinction and cortico-subcortical damage the paraventricular occipital white matter and the dorsolateral frontal cortex were most often involved. By contrast, when neglect was also present, the lesions clustered in the inferior parietal lobule. These data suggest, from an anatomical perspective, that partly different neural mechanisms may underlie neglect and extinction. The comparatively high frequency of subcortical lesions involving the ascending pathways may be a neural correlate of a sensory component of extinction.