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Patients with cystic echinococcosis ( CE) can harbour cysts for years or even decades, apparently without effect of the immune system on the metacestode. Although several immune evasion mechanisms by echinococcal cysts have been described, it is unclear whether the human leucocyte antigen ( HLA) system plays a role in the susceptibility or resistance to CE in humans. HLA-G molecules are known to exert a suppressive action on dendritic cells maturation and on natural killer ( NK) cells functions, therefore hampering T-cell responses and NK cytolysis. HLA-G plays an important role in immune tolerance, is involved in foetus and in allotransplant tolerance, and may be involved in tumoral and viral immune evasion. In this study, we assessed the presence and levels of soluble HLA-G ( sHLA-G) in patients with CE using a commercial ELISA kit to determine whether host's HLA-G may have a role in the course of human CE. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to compare the reliability of the ultrasonography (US) evaluation of joint damage in patients with hemophilia conducted by a radiologist and non-radiologist. Methods used in the 3-year-study which involved 36 patient with haemophilia and evaluated elbow, knee and ankle joints of each patient are offered. Results indicate that US evaluation can be performed by a trained non-radiologist and is usefulat every clinical assessment of haemophilic patients.

To investigate the usefulness of serum cytokine levels in the diagnosis of active cystic echinococcosis, we evaluated the cytokine profile of patients with hepatic cystic echinococcosis in different cyst stages, CE 1-2 (active), CE3a-3b (transitional) and CE4-5 (inactive). Ex vivo assessment of Th1 (IL12, TNFα) and Th2 (IL4, IL10) cytokines in sera was carried out using ELISA. Percentages of positive samples and median levels of IL12, TNFα and IL10 did not differ significantly between groups. However, patients with CE3b cysts, a stage clinically unresponsive to treatments, had statistically significantly higher median levels of IL4 and percentage of positive samples for IL4. We conclude that the analysis of serum cytokine dosage, at least in its present form, is not useful as a marker of cyst activity. However, our results support recent findings suggesting the chronic activity of CE3b cysts and suggest that this might be partly because of a skewed Th2 response. [ABSTRACT FROM AUTHOR]

Currently, pioglitazone and rosiglitazone are the thiazolidinediones available for clinical use. In the literature, there are different studies concerning the efficacy, safety and tolerability of thiazolidinediones as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin alone. Metformin and thiazolidinediones are both antihyperglycaemic drugs, both lower blood glucose concentrations in type 2 diabetes without causing overt hypoglycaemia and both require the presence of insulin to generate their therapeutic effects, but act without stimulating insulin secretion. Some authors reported that the improved glycaemic control obtained with thiazolidinediones is associated with an increase in body weight with an estimated 2–3 kg weight gain for every 1% decrease in HbA1c which could negate some of the benefits of the improved metabolic control. Some other authors, instead, reported that thiazolidinediones give a better improvement in the glycaemic control compared with metformin alone without giving weight gain. The emerging discrepancies from these studies could be because of the study design, the patient selection, the degree of glycaemic control and/or the methods to measure body weight. We have undertaken a thorough literature search on Medline and Embase to evaluate the effects of thiazolidinediones plus metformin combination in people with diabetes on the body weight. [ABSTRACT FROM AUTHOR]

Birth weight is known to be a direct indicator of perinatal mortality and a clear predictor of adult pathologies too. It has been correlated with several causes of mortality in adulthood: low birth weight with diabetes, nephropathy and cardiovascular diseases and high birth weight with autoimmune diseases and cancer. In genome-wide studies, an extended human leucocyte antigen ( HLA) region has been linked to birth weight variation. We focused our attention on the HLA haplotypes marked by HLA-A, HLA-B and HLA-DRB1 polymorphisms in 1206 healthy Caucasian newborns belonging to the Cord Blood Bank of Pavia (Italy) and their mothers, aiming to investigate the association between this restricted HLA region and birth weight variation. In our study, the HLA-B*38;DRB1*13 haplotype showed an ascending trend among centiles addressing to the high foetal weight. The HLA-A*02;B*15 haplotype showed a descending trend among centiles addressing to the low foetal weight. Besides the acknowledged correlation between the HLA-A*02 and HLA-B*15 alleles (as well as low birth weight) and type I diabetes and between the HLA-B*38 and HLA-DRB1*13 alleles (as well as high birth weight) and several autoimmune diseases, we cannot predict if our babies, healthy at birth, will suffer from these pathologies during life. Nevertheless, our data point to the HLA telomeric end for markers linked to the low birth weight and to the HLA centromeric end for markers linked to the high birth weight, thus limiting the region involved in birth weight variation, which still represents a useful predictor of disease risk in adulthood. [ABSTRACT FROM AUTHOR]

Background Guidelines for kidney function monitoring and antiretroviral drug dosing are available and respectively refer to glomerular filtration rate and creatinine clearance (CrCl). Objective The aim of the study was to compare kidney function estimates vs. measured 24-h CrCl in HIV-infected subjects. Methods A cross-sectional design was used, with comparison of Cockcroft–Gault (CG), original and simplified modification of diet in renal disease (MDRD) equations vs. measured 24-h CrCl. Subjects were HIV-infected, 18–70 years old, without pre-existing kidney disease. Results Results are presented as mean (±standard deviation), unless otherwise stated. The study population consisted of 90 patients, of whom 71% were male, with a mean age of 45 years (±6.5 years). At the time of evaluation, the mean body mass index was 23 (±3.3); mean serum creatinine was 0.91 mg/dL (±0.2 mg/dL); and mean blood urea nitrogen (BUN) was 34.7 mg/dL (±10.6 mg/dL). Differences between paired methods were all significant ( P<0.00001), except between CG and simplified MDRD ( P=0.21; Pearson r=0.81). In univariate analysis, male gender, CD4 nadir, hepatitis B virus coinfection, BUN and current CD4 cell count showed a significant positive correlation ( P<0.2) with the difference between measured 24-h CrCl and either CG or simplified MDRD estimates. In multivariate analysis, only BUN showed a significant positive correlation ( P<0.05). Conclusions Estimates were lower than the measurements of 24-h CrCl. Original MDRD estimates were lower than those with other equations. CG and simplified MDRD estimates showed a satisfactory correlation. [ABSTRACT FROM AUTHOR]

Abstract: Chronic pain is a situation that bring patients to ask for a medical intervention and can be originated from many different pathologic conditions. Nowadays, recent advancements in pain treatment have made possible to control pain in many patients, allowing them to return to daily activities. Anaesthesiologists are the modern pain specialists, and must know and define the origin of pain in every case: the comprehension of pain mechanisms gives them the possibility for a planned strategy of treatment. In this work we perform a overview about the “state of the art” of pain treatment in Italy analyzing what are the problems that require to focalize our attention. Therefore, sometimes many visits are necessary for a correct diagnosis and successful therapy. Pain management is still a young speciality, and the Italian pain specialist is often a self made expert who needs proper structures and dedicated people: the result is a different treatment not only between the hospitals but also in the same pain conditions. Although it seems that many of the new techniques used to control pain are successful, few studies and controlled trials have been done to verify long-term efficacy and potential adverse effects. [Copyright &y& Elsevier]

Objective Our previous studies on CD4-guided therapy interruption (TI) showed that the durations of the first and second TIs were similar if antiretroviral therapy (ART) was resumed at a level of the CD4 cell count similar to or higher than the nadir CD4 T-cell count. Therefore, in a strategy of repeated CD4-guided TI, it is important to know which factors predict the time for the CD4 T-cell count to return to nadir (TRN). Methods From a cohort of 125 patients who interrupted ART, 92 patients who reached a CD4 T-cell count similar to the nadir count were included in the study. Results The median TRN was 12.3 months. In the multivariate analysis, younger age ( P=0.011), lower pre-ART HIV RNA ( P=0.022) and female gender ( P=0.045) were associated with a longer TRN. After TI there were 11 clinical events in the group of patients whose nadir CD4 count was >200 cells/μL. Most of these events occurred when the TI was prolonged beyond the TRN. Conclusions The factors predicting the TRN were age, HIV RNA pre-ART and gender. Resumption of therapy at a CD4 cell count similar to the nadir CD4 count appears to protect against the development of clinical events. Given the observational nature of this study, no conclusions can be drawn regarding the possible application of TI in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose central retina vein occlusion(CRVO) is a retinal vascular disorder associated with various degrees of retinal ischemia leading to macular oedema and visual acuity loss. The standard method to detect and measure the macular oedema is the Optical Coherence Tomography(OCT). The focal electroretinogram (FERG) is a part of the electroretinography that investigate functionally the macula.The aim of our study was to investigate the relationship between visual acuity, morphologic aspects and functional results in CRVO. Methods we examined 24 eyes affected by CRVO. All the patients had complete survey comprehending ETDRS visual acuity(VA), FERG, OCT. The FERG was performed via ERG dome, using a background light of 300 cd/m2 and a led stimulus alternating at 5,1 hz. The OCT values of macular volume and thickness, the a and b wave values of latency and amplitude were collected and analyzed. The results were matched with 19 eyes not affected of the same sample and with 20 eyes of healthy subjects. Multiple statistical relationship analysis of the r and p were done by mean of Kruskal‐Wallis test. The sensitivity and specificity were analyzed with Roc curve. Results we do not found correlations between VA and OCT macular volume and thickness. A significant correlation with VA was found in a and b FERG amplitudes between the CRVO group, healthy subjects and the healthy eyes of CRVO group and also between the healthy eyes of CRVO and healthy subjects.Significant sensitivity and specificity (72.1 and 80 respectively) were found in Roc curve Conclusion in our study functional alterations of the FERG correlate and probably precede VA loss [ABSTRACT FROM AUTHOR]

Purpose Joubert syndrome (JS) is a rare autosomal recessive congenital malformation of the brainstem and cerebellar vermis. The pathology can be associated with retinal dystrophy (RD). In a previous study we presented the data of retinal involvement and their relationship with electrophysiology in 26 JS patients. The longitudinal data are shown in a part of this sample. Methods All the children had repeated clinical examinations. The electroretinogram (ERG) was performed without sedation. One recording skin electrode was placed on the bridge of the nose. The stimulation included the maximal combined response and a 30 Hz response after a brief adaptation. For the patterned visual evoked potentials (PVEP) a sequence of checks of 15, 30, 60, 120 and 300 minutes of arc was presented. All the JS children had both ERG and PVEP repeated from 2 to 4 times. A total of 13 JS affected children for the ERG and 12 for the PVEP were analyzed. Comparisons between percentage of reliable responses were performed by Fisher exact test. Results A significant difference between JS children with and without RD in 30 hz ERG (p=0.050) and 120, 60, 30, and 15 minutes of arc (p=0.006,0.002,<0.001,<0.001 respectively) was found. Conclusion ERG and PVEP repeated measures are valuable means for the diagnosis and follow‐up of RD in JS (patients). [ABSTRACT FROM AUTHOR]

Purpose To compare electrophysiological data in a group of patients with Joubert syndrome (JS). Methods We enrolled 26 JS patients. They underwent to complete ophthalmological assessment and functional analysis by mean of electroretinogram (ERG) and patterned evoked potentials (pVEPs) recorded in awake conditions. Patients were divided into 2 groups, depending on the presence of retinal dystrophy at clinical evaluation. We compared data from electrophysiological assessment between three groups of eyes: 1) JS subjects with retinal dystrophy (RD‐JS): 15 patients 2) JS subjects without retinal dystrophy (NRD‐JS): 11 patients 3) Control (CTRL) eyes: 18 patients Results Our three groups did not statistically differ in age. In the RD‐JS, traces were really poor, mostly the 30 Hz and "a" component, or not measurable at all. Though, for the "b" trace, it was possible to measure reliable signal in 7 of 15 patients. As a result of the statistical analysis (ANOVA Kwallis with adjust p values for two comparisons) mean ERG amplitudes and latencies were reduced and delayed respectively, not only in the analysis "RD‐JS vs CTRL" and "RD‐JS vs NRD‐JS", but also, for some parameters, between NRD‐JS and the CTRL. Conclusion The electrophysiological alterations in the ERG and pVEPs recordings might be an index of subclinical involvement or imply both a central retinal alteration and a central nervous system disease. [ABSTRACT FROM AUTHOR]

An abstract of the study "Quality of life is independent of time since heart transplant in clinically stable patients," by C. Klersy and colleagues is presented.

Presents a commentary on an study regarding the hepatitis B vaccination in preterm infants. Exclusion of infants with common complications; Determination of final seropositive rates and geometric mean titre; Recommendation of delaying vaccination.

The aim of the study was to investigate whether polymorphisms of the HLA class II, tumour necrosis factor (TNF) and transporter associated with antigen processing (TAP) genes influence the response toα-interferon in patients with chronic hepatitis C. Twenty-seven sustained responders and 55 non-responders toα-interferon monotherapy were investigated. HLA-DRB1, DQA1, DQB1, TNFA, TNFB, TAP1 and TAP2 alleles were determined by PCR-based molecular techniques. Sustained virological response was defined as undetectable serum hepatitis C virus (HCV) RNA for at least 3 years after the end of treatment. Probability (P) values were corrected for the number of alleles tested (Pc). Viral genotype 1b was more frequent in responders than in non-responders (56% vs. 26%,P = 0.009). HLA-DQB1*02 occurred less frequently in responders than in non-responders (14.8% vs. 29%,Pc not significant). HLA-DRB1*11 and DQB1*0602 were found in 22.2% and 9.3% of responders and in 10.9% and 1.8% of non-responders, respectively (Pc not significant). There was no difference in the distribution of TNF alleles in the two groups. Twenty-four (88.8%) responder patients as compared with 34 (61.8%) non-responders were TAP1*0101 homozygous (Pc not significant). Thus, in European Caucasoids with chronic hepatitis C, we could not demonstrate a strong association between HLA class II, TNF, and TAP gene polymorphisms and response to interferon treatment. [ABSTRACT FROM AUTHOR]

Background & Aims: Ultrasound is the imaging modality most widely utilized in the general population for diagnostic purposes. Controlled attenuation parameter is a novel noninvasive method for assessing steatosis. Our aim was to investigate whether the clinical value of controlled attenuation parameter in patients referred for abdominal ultrasound examinations is affected by liver fibrosis., Methods: Consecutive patients referred for abdominal ultrasound examinations were enrolled. Controlled attenuation parameter and liver stiffness were assessed with the FibroScan (Echosens, France). Liver fibrosis was staged according to published cutoffs of liver stiffness measurements. Pearson's or Spearman's rank correlation coefficient was used to test the association between two study variables. Optimal cutoff of controlled attenuation parameter for diagnosing liver steatosis (S≥2) was 256 dB/m. The diagnostic performance and accuracy of dichotomized controlled attenuation parameter, ultrasound and body mass index were analysed using the imperfect gold standard methodology., Results: A total of 726 subjects (464 males and 262 females) were studied. Five hundred and eight-nine (81.1%) patients were affected by chronic viral hepatitis. Correlation of controlled attenuation parameter with ultrasound score was 0.48 and 0.57 in patients with and without chronic viral hepatitis respectively. In patients with chronic viral hepatitis, ultrasound, dichotomized controlled attenuation parameter and body mass index showed performance of 58.2%, 82.3% and 46.7%, respectively, whereas in patients without chronic viral hepatitis, the performance was 86.4%, 68.6% and 48.6% respectively., Conclusions: In patients with chronic viral hepatitis and advanced liver fibrosis, controlled attenuation parameter performs better than ultrasound for assessing liver steatosis, whereas in patients without viral hepatitis and with nonsignificant liver disease ultrasound shows the best performance., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: The study aimed to evaluate the tissue expression of molecules involved in intracellular signalling pathways as predictors of response to sorafenib in advanced hepatocellular carcinoma (HCC)., Methods: We considered 77 patients enrolled into three prospective trials of sorafenib treatment for whom pretreatment tumour tissue was available. The tissue expression of β-catenin, glutamine synthetase (GS), phosphorylated extracellular signal regulated kinase (pERK), phosphorylated v-akt murine thymoma viral oncogene homolog (pAKT) and vascular endothelial growth factor receptor-2 (VEGFR-2) was analysed by immunostaining. Stains were scored semiquantitatively and compared with a reference group of 56 untreated HCCs., Results: Overall, the expression of antigens was comparable between treated and untreated patients. Shorter progression-free survival (PFS) and overall survival (OS) were associated with increased pERK staining (≥ 2+ scores) (PFS: 75th percentile 4.4 vs 8.4 months; P = 0.01; OS: 75th percentile 7.0 vs 15.0 months; P = 0.005) and VEGFR-2 staining (≥ 2+ scores) (PFS: 75th percentile 3.8 vs 7.0 months; P = 0.039; OS: 75th percentile 6.3 vs 15.0 months; P = 0.004). At multivariate analysis, both pERK and VEGFR-2 staining maintained an independent effect on OS (HR 2.09; 95% CI, 1.13-3.86, P = 0.019 and HR 2.28; 95% CI, 1.13-4.61, P = 0.021 respectively). No effect was observed for the other tested biomarkers., Conclusions: Elevated tissue expression of pERK and VEGFR-2 was predictive of poor outcome in advanced HCC treated with sorafenib., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Problem: To target gestational diabetes mellitus (GDM) by means of temporal variation in pregnancy-associated plasma protein A (PAPP-A) and soluble human leukocyte antigen-G (sHLA-G)., Method of Study: Retrospective analysis of PAPP-A and sHLA-G blood levels in historical samples of 112 GDM and 112 controls, drawn at first trimester, and prospective study in 18 GDM and 105 controls collected in triplicate along the pregnancy. Six hundred and sixty-five samples were analyzed., Results: Gestational diabetes mellitus had significantly lower first-trimester PAPP-A concentrations than controls (2343±1519 versus 2996±1955 mU/mL, in retrospective brunch and 2490.57±1828.52 versus 3240.84±1930.69 mU/L in prospective one, P<0.001). First-trimester sHLA-G level was significantly lower in GDM than in controls (52.88±59.69 versus 66.81±50.14 ng/mL, P<0.001) and increased during gestation in diabetic women showing an opposite trend with respect to the controls., Conclusion: PAPP-A and sHLA-G are independent markers of GDM. Quantitative variations during pregnancy help to early unravel the onset of GDM., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: Aim of this study was to assess if host (immunogenetic traits, age, sex), exogenous (alcohol) or viral factors (viral type, past HBV infection) might affect the progression of chronic hepatitis C to liver decompensation or the development of HCC in a cohort of patients exposed to a single blood transfusion prior to the introduction of anti-HCV screening., Methods: Two hundred and forty-eight patients with a history of a single exposure to blood or blood products prior to 1990 were retrospectively considered. Patients were devoid of other risk factors of liver disease or immunosuppression and naïve to antiviral therapies. Eight baseline variables were assessed: age at transfusion, sex, HBV core antibody, immunogenetic profile (DRB1*11, DRB1*1104, DRB1*07), HCV genotype and alcohol consumption., Results: The follow-up was 22 (SD: 11) years. Sixty-eight patients (27%) progressed to hepatic decompensation over a median period of 22.5 years (IQR: 14-30) and 41 patients (16%) developed HCC over a median period of 31 years (IQR: 24-38). The cumulative incidence of liver failure was 0.4% (95% CI: 0.1-3.1), 4.9% (95% CI: 2.6-9.3) and 16.2% (95% CI: 10.4-24.7) at 10, 20 and 30 years after blood transfusion respectively. By univariate analysis, only age at transfusion was correlated with the risk of decompensation. Stratifying the age of transfusion by tertiles, the incidence of hepatic decompensation was 0.7% per year in patients transfused at ≤24 years of age as compared to 1.2% and 1.9% per year in those transfused at 25-35 and >36 years of age respectively (HR: 5.5, 95% CI: 2.78-10.7, P<0.001). The risk of HCC development was correlated by univariate analysis with age at transfusion (as continuous variable, HR: 1.12, 95% CI: 1.08-1.16 per year of age, P<0.001, >36 compared to ≤24 years, HR: 10.3, 95% CI: 3.9-26.9, P<0.001) and male sex (HR: 4.2, 95% CI: 1.7-10, P=0.001). Multivariate analysis confirmed age at transfusion and male sex as independent predictors of HCC development [HR: 1.12 per year (95% CI: 1.08-1.16), P<0.001 and HR: 5.4 (95% CI: 2.2-13.2), P<0.001 respectively]., Conclusions: In patients with transfusion-acquired HCV infection, age at transfusion affects the risk for hepatic decompensation. Age at transfusion and male sex are independent risk factors for HCC development., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

What Is Already Known About This Subject: * Mycophenolic acid (MPA) is a potent, selective and reversible inhibitor of inosine 5'-monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme for de novo guanosine triphosphate biosynthesis. * The large IMPDH interindividual variability could be responsible for the differences in therapeutic effects and side-effects observed with MPA. * Induction of IMPDH activity has been observed in whole blood during immunosuppressive therapy., What This Study Adds: * Our data were acquired in long-term mycophenolate mofetil-treated renal transplant recipients on different combinations of immunosuppressive agents (ciclosporin, tacrolimus, sirolimus) and with different treatment duration (up to 8.8 years post transplant). * The increasing trend in IMPDH activity that we observed throughout our 12-month observation period was significantly higher in rejecting than in nonrejecting subjects., Aims: Long-term mycophenolate mofetil (MMF) therapy may induce inosine 5'-monophosphate dehydrogenase (IMPDH) activity in peripheral blood mononuclear cells (PBMCs), thus decreasing MMF immunosuppressive properties. Pharmacodynamic monitoring was used to investigate whether biological activity is altered after long-term therapy., Methods: IMPDH activity was measured in PBMC samples from 54 stable kidney transplant patients, already on MMF (for at least 3 months), before (t(0)) and 2 h after (t(2)) MMF morning dose administration; levels were monitored for up to 15 months, together with total mycophenolic acid (MPA) and free MPA concentrations., Results: During the 15 months' monitoring, t(0) IMPDH activity in transplant recipients increased from 5.9 +/- 3.7 nmol h(-1) mg(-1)[95% confidence interval (CI) 4.9, 6.9] to 9.0 +/- 3.9 nmol h(-1) mg(-1) (95% CI 7.2, 10.8), with an intra- and interpatient variability of 28% and 42%. Five patients experienced acute rejection during the follow-up: t(0) IMPDH activity was increased during rejection vs. nonrejection, and the trend was significantly higher in rejecting than in nonrejecting subjects for the whole monitoring period., Conclusions: Even though a correlation has been found between IMPDH activity and rejection, its efficacy as a predictive tool in long-term transplant outcomes may be affected by high interpatient variability; on the other hand, continuous monitoring of the IMPDH trend could make an effective prognostic parameter of rejection. Other trials also including pre-transplant data on both IMPDH expression and activity are warranted to better assess their role as biomarkers for MPA effect in clinical practice.

Background: Helicobacter pylori infection is a frequent infection mainly acquired in childhood. Even if the infection is almost invariably associated with mild to severe gastro-duodenal lesions, no specific clinical picture has been identified. The aim of this study was to evaluate the presence of dyspeptic symptoms and their relationship with the presence of H. pylori infection in the first two decades of life., Materials and Methods: A school-population sample size of 808 subjects from 6- to 19-year-olds was investigated for the presence of gastrointestinal tract symptoms and evaluated by a 13C-urea breath test for H. pylori infection. The relationship between clinical findings and H. pylori infection was evaluated by chi2 statistic or Fisher's exact test, as appropriate., Results: Symptoms of dyspepsia were identified in 45% of subjects, while the picture of ulcer-like and dysmotility-like forms were present in 3-4%. H. pylori infection was demonstrated in 95 (11.8%) subjects, 49.5% of them without symptoms. Severe epigastric pain and ulcer-like dyspepsia were significantly associated with H. pylori infection, while recurrent abdominal pain or dysmotility-like dyspepsia were not., Conclusions: Dyspeptic symptoms are frequent in children, and its association with H. pylori infection is more evident than with recurrent abdominal pain. The age at which the infection is acquired seems to be under 6 years of age.