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The pediatric ultrasound measurement of the inferior vena cava (IVC) and aorta (AO) with the study of the collapsibility index (CI) and of IVC-to-AO ratio (IVC/AO) can provide clinicians in the acute care setting with information on abnormal volume status but one of the major limitations is a lack of reference normal values by body surface area (BSA) and age. The aim of this study was to provide reference ranges for the sonographic measurement of IVC, AO, and IVC/AO ratio in healthy Caucasian Italian children.We enrolled prospectively 516 healthy Caucasian Italian children aged between 1 month and 16 years. Echocardiographic IVC and AO diameters were collected and presented separately for children aged ≤1 year and for children aged over 1 year. For children1 year we categorized subjects into 3 years classes. CI and IVC/AO for the systolic aortic diameter were then calculated. For children over 1 year, age reference ranges were age-related or BSA-related; for children of ≤1 year, reference ranges were determined with their 90% confidence intervals regardless of age and of BSA.Tables and charts with reference ranges for all the echocardiographic measurements are presented for children aged1 year according to age and BSA. The equations to obtain percentile and Z-score for each echocardiographic measurement are provided. The reference ranges for children aged ≤1 year are shown considering the small 90% confidence intervals for upper and lower limits. CI was 30% (SD 17%) in children1 year and 36% (SD 16%) in children1 year. IVC/AOs showed age-dependent values from 0.83 (SD 0.20) age1 year to 1.22 (SD 0.31) in older subjects.We report reliable reference ranges for echocardiographic measurement of IVC, AO, CI, and IVC/AO for a Caucasian Italian healthy pediatric population.

we performed a meta-analysis to assess the usefulness of HLA testing for Narcolepsy diagnosis in four major ethnical groups: Asians, Afro-Americans, Amerindians and Caucasians.PubMed, EMBASE, Web of Science, Scopus and Cochrane databases were searched for articles in English and French published before October 2017 on HLA class II alleles in Narcolepsy. We included case-control studies, cross-sectional and retrospective cohort studies with patients diagnosed following the International classifications of sleep disorders (1990-2012) and ethnically matched controls. Following PRISMA guidelines, two investigators independently extracted data according to the inclusion criteria listed in PROSPERO CRD42017058677. A third researcher was consulted for discrepancies. We extracted and pooled adjusted OR using random-effect models. We verified the strength of the association between HLA-DQB1*06:02 and the worldwide distribution of Narcolepsy type 1 (NT1) and type 2 (NT2); furthermore, we pooled the OR measuring the association between HLA-DQB1*06:02 and NT1, NT2 and hypersomniacs.We identified 511 titles. Of these, 12 case-control studies were included, for a total of 2077 NT1 patients, 235 NT2 patients, 161 hypersomniacs and 7802 controls. In the population-stratified analysis, HLA-DQB1*06:02 conferred an increased risk for NT1 (OR: 24.1, IC: 14.6-39.5, p 0.001) and NT2 (OR: 3.9; IC: 2.2-6.8, p 0.001). For NT1 the pooled estimated positive Likelihood Ratio (LR+) was 5.94 (IC: 3.71-9.51) and the negative Likelihood Ratio (LR-) was 0.23 (IC: 0.16-0.33); for NT2 LR+ was 3.35 (IC: 2.08-5.38) and LR- 0.72 (IC: 0.63-0.81). Moreover, for hypersomniacs LR+ was 1.436 (IC 0.668-3.089) and LR- 0.903 (IC 0.714-1.142).Our data support the preponderant role of HLA-DQB1*06:02 in susceptibility to NT1/NT2 across all ethnicities. HLA-DQB1*06:02 negativity should make clinicians cautious in excluding other diagnoses.

Background: EGFR inhibition leads to the production of reactive oxygen metabolites, causing skin inflammatory reactions. Lycopene has an extreme antioxidant activity and, due to its hydrophobic structure, accumulates specifically in the skin. Methods: To assess lycopene effectiveness in reducing skin toxicity induced by panitumumab, 28 patients received lactolycopene or placebo in a phase-II PASTO study. Patients were evaluated at the beginning of each cycle and data were analyzed as the difference in mean grade of skin toxicity, frequency and duration of > G2 skin toxicity and frequency of tetracyclines administration. Lycopene, β-carotene and malondialdehyde plasma concentrations were analyzed to measure antioxidant consumption and oxidative stress. Findings: In the placebo group, ten out of 15 patients (66·67%), developed a > G2 skin toxicity, during 36 out of 92 cumulative cycles (39·1%), versus 3 out of 13 (23·08%), during 8 out of 64 cumulative cycles (12·5%) in the lactolycopene group. The time to the appearance of > G2 skin toxicity was different in the two groups (p= 0.0007 logrank test). Mean value of skin toxicity during treatment was 2·4 and 1·4 for placebo and lactolycopene group, respectively. Tetracyclines were administered for > G2 skin toxicity according to the protocol. Mean plasma concentration of lycopene and β-carotene decreased during treatment compared to day 0 (-141·94% and -157·22% respectively) in the placebo group, with a +109·36% mean malondialdehyde concentration increase. In contrast, in the lactolycopene group, mean plasma lycopene concentration increased during treatment (+94·18%), with a mean malondialdehyde concentration decrease (-68·83%) and a mean β-carotene concentration decrease (-105·5%) smaller than in the placebo group . Interpretation: Despite the limited number of patients, results clearly show lycopene effectiveness in reducing skin toxicity in patients treated with panitumumab. In our series lactolycopene administration was able to protect tissues from oxidative stress and to replenish antioxidants consumption. Trial Registration: registered in ClinicalTrials.gov (PaSTo – Clinicaltrials.gov: NCT 03167268) Funding Statement: AMOlavitaONLUS, Indena Spa. Declaration of Interests: MM1 is the vice-president and MP the treasurer of AMOlavitaONLUS. AMOlavitaONLUS is the sole owner and it holds all the ownership rights on the international patent application entitled “Use of carotenoid derivatives to reduce the toxicity and increase the efficacy of antiEGFR antitumor treatments” (N°PCT/IB2018/050229). MM1 and MP are exclusively inventors of the patent and they have no ownership right on the patent. Indena Spa, who supplied free of charge lactolycopene for the Pasto Clinical Trial, is not the owner of the patent for lactolycopene production. All other authors declare no competing interest. Ethics Approval Statement: The protocol was approved by the ethics committees of all participating institutions. Written informed consent was obtained from all patients.

Purpose To evaluate feasibility and efficacy of transanastomotic self-expandable polytetrafluoroethylene stent graft placement for salvage of radiocephalic arteriovenous fistulae (RCAVFs). Materials and Methods From 2008 to 2016, 26 patients (21 male; age, 38–80 y) with dysfunctional RCAVFs for juxtaanastomotic lesions that were unresponsive to angioplasty underwent transanastomotic stent graft placement. Stenotic and thrombotic lesions were included. All were deemed unsuitable for surgical revision. Patency rates were calculated per Kaplan–Meier method. A Cox analysis was used to identify influencing factors. Results Thirty-two stent grafts (6 patients had 2 stents) were deployed. Anatomic and clinical success were achieved in all patients; no major complications occurred. Mechanical and/or pharmacologic thrombolysis was performed in 6 cases before stent graft deployment. During follow-up (median, 34.7 mo; range, 1.9–102.7 mo), 17 repeat interventions were required in 10 patients (43 procedures overall), for an endovascular intervention rate of 0.27 per year. At 3, 6, 12, and 24 months, primary patency (PP) rates were 96% ± 4 (95% CI, 75%–99%), 83% ± 7 (95% CI, 61%–93%), 78% ± 8 (95% CI, 55%–90%), and 69% ± 10 (95% CI, 46%–84%). The corresponding assisted PP rates were 96% ± 4 (95% CI, 76%–99%), 96% ± 4 (95% CI, 76%–99%), 92% ± 5 (95% CI, 71%–98%), and 82% ± 8 (95% CI, 60%–93%). Five AVFs were ultimately abandoned. Per Cox analysis, arterial diameter ≥ 4 mm was associated with better PP ( P = .032). Conclusions Transanastomotic stent graft placement for RCAVF salvage is feasible and safe, providing patency rates comparable with historical endovascular and surgical data. Its role should be evaluated in larger studies.

Juvenile Idiopathic Arthritis (JIA) is characterized with a variable pattern of articular involvement and systemic symptoms and, thus, it has been classified in several subtypes. Genetic predisposition to JIA is mainly due to HLA class II molecules (HLA-DRB1, HLA-DPB1), although HLA class I molecules and non-HLA genes have been implicated, too. Here, we carried out a meta-analysis including selected studies designed to assess HLA genetic background of JIA patients, compared to healthy controls; particularly, we focused our attention on HLA-DRB1. In summary, our meta-analysis showed four main findings regarding HLA-DRB1 locus as a genetic factor of JIA: i) HLA-DRB1*08 is a strong factor predisposing to JIA, both for oligo-articular and poly-articular forms (oJIA > pJIA); ii) HLA-DRB1*01 and HLA-DRB1*04 may be involved in the genetic predisposition of Rheumatoid Factor (RF) positive forms of JIA; iii) HLA-DRB1*11 was confirmed to be predisposing to oligo-articular JIA; iv) HLA-DRB1*04 was confirmed to have a role in systemic JIA. Importantly, RF positivity seems to select the JIA clinical subset with the strongest immunogenetic similarities with adult rheumatoid arthritis.

Epidermal Growth Factor Receptor (EGFR) inhibition leads to the production of reactive oxygen metabolites causing skin inflammatory reactions. Anti-EGFR therapies are frequently associated with skin toxicities which often cause treatment delay and impairment to patient quality of life. Lycopene is a compound in the carotenoid group with an extreme antioxidant action which accumulates in the skin due to its hydrophobic structure. In a pilot study, we describe lactolycopene effectiveness in reducing skin toxicity and protecting tissues from oxidative stress in patients treated with panitumumab. Despite the limited number of patients, we show an absolute reduction of skin grade 2–3 toxicity in 41% of patients and 46% of panitumumab cumulative cycles in the experimental group versus placebo; lactolycopene administration was able to abolish malondialdehyde (MDA) production, a biomarker used to measure lipid peroxidation in the organism, and replenish antioxidant consumption in the course of anti-EGFR therapy. Trial registration: Clinicaltrials.gov NCT 03,167,268 (Pasto trial).

none 11 no BACKGROUND: Experts and scientific society guidelines recommend that rapid on-site evaluation (ROSE) be used with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to optimize lung cancer genotyping, but no comparative trial has been carried out to confirm and quantify its usefulness. METHODS: To assess the influence of ROSE on the yield of EBUS-TBNA for a multigene molecular analysis of lung cancer samples, consecutive patients with suspected or known advanced lung cancer were randomized to undergo EBUS-TBNA without ROSE (EBUS arm) or with ROSE (ROSE arm). The primary end point was the rate of the successful accomplishment of the institution's clinical protocol for molecular profiling of nonsquamous non-small cell lung cancer (EGFR and KRAS testing, followed by ALK testing for tumors with EGFR and KRAS wild-type status). RESULTS: Complete genotyping was achieved in 108 of 126 patients (85.7%) (90.8% in the ROSE arm vs 80.3% in the EBUS arm, P = .09). The patients in the ROSE arm were less likely to have samples that could be used only for pathologic diagnosis because of minimal tumor burden (0 vs 6, P = .05), and were more likely to have the bronchoscopy terminated after a single biopsy site (58.9% vs 44.1%, P = .01). CONCLUSIONS: ROSE prevents the need for a repeat invasive diagnostic procedure aimed at molecular profiling in at least one out of 10 patients with advanced lung cancer and significantly reduces the risk of retrieving samples that can be used only for pathologic subtyping because of minimal tumor burden. Trisolini, Rocco; Cancellieri, Alessandra; Tinelli, Carmine; de Biase, Dario; Valentini, Ilaria; Casadei, Gianpiero; Paioli, Daniela; Ferrari, Franco; Gordini, Giovanni; Patelli, Marco; Tallini, Giovanni Trisolini, Rocco; Cancellieri, Alessandra; Tinelli, Carmine; de Biase, Dario; Valentini, Ilaria; Casadei, Gianpiero; Paioli, Daniela; Ferrari, Franco; Gordini, Giovanni; Patelli, Marco; Tallini, Giovanni

Aim To evaluate the effects on glycemic excursions during bicarbonate dialysis (BHD) compared to hemodiafiltration (HDF) in type 2 diabetic or not diabetic patients affected by end-stage renal disease (ESRD). Material and Methods Thirty-six patients (20 affected by type 2 diabetes mellitus, and 16 not diabetic patients) were evaluated and underwent BHD dialysis, followed by HDF dialysis two days later. All patients underwent also glucose continuous monitoring system, using i Pro Continuous Glucose Monitor System (Medtronic MiniMed) starting just before the BHD, and ending five days later, two days after the HDF dialysis. Glycemic control was estimated as the mean blood glucose (MBG), the area under the glucose curve above 70mg/dl (AUC >70 ) or 180mg/dl (AUC >180 ), and the percentage of time above 70mg/dl (t >70 ) or 180mg/dl (t >180 ). Intraday glycemic variability was assessed as the standard deviation (SD), M value, and the mean amplitude of glycemic excursions (MAGE). Day-to-day glycemic variability was assessed as the mean of daily difference (MODD), that is the mean of the absolute difference among glucose values taken on 2 consecutive days at the same time. Results glycemic control was better with HDF: MBG, and AUC >180 were lower during HDF compared do BHD. We also observed a significant decrease of glycemic excursions during HDF dialysis: SD, M value, and the MAGE value were lower with HDF. The MODD value was significantly changed in BHD group, while no differences were recorded during HDF. Conclusion HDF seems to greater reduce glycemic excursions during the treatment compared to BHD.

Autoimmune rheumatic diseases in pregnancies are associated with increased adverse obstetric outcomes. We compared maternal soluble human leucocyte antigen-G (sHLA-G) blood levels in subjects with a rheumatic disease preexisting pregnancy and unaffected controls. Third-trimester blood maternal sHLA-G concentrations were significantly higher in subjects with rheumatic diseases than in controls (mean 93.1ng/ml [SD 42.1] vs 58.1ng/ml [SD 96.3], p=0.003). Cord blood sHLA-G concentrations were significantly higher in rheumatic disease than in those born to control mothers (median 41.2ng/ml [IQR: 3.3-44.0] vs 17.9ng/ml [IQR: 17.2-88.1], p=0.007). A strict positive correlation (r=0.88, p

Human papillomavirus (HPV) oncogenic activity is the result of viral oncogene E6 and E7 expression in infected cells. Oncogene expression analysis is, however, not part of the routine diagnostic evaluation of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) since it requires fresh tumor tissue. We compared the diagnostic accuracy of several methods commonly employed for HPV characterization in OPSCC with the results of the newly available HPV E6/E7 mRNA in situ hybridization (ISH) on formalin-fixed, paraffin-embedded biopsy samples, in order to establish if the latter should be introduced in the diagnostic routine to increase accuracy when fresh tissue is not available. p16 immunostain, DNA ISH for high-risk HPV genotypes, SPF LiPA amplification and genotyping, and HPV16 E6 amplification were performed on 41 consecutive OPSCC samples. Twenty (48.7%) cases were positive by mRNA ISH; sensitivity and specificity were 100% and 90% for p16, 90% and 100% for DNA ISH, 70% and 76% for SPF10 LiPA, 90% and 76% for E6 amplification. A diagnostic algorithm considering p16 immunostain as first step followed by either high-risk HPV DNA ISH or HPV16 E6 amplification in p16-positive cases correctly characterized 90% of mRNA-positive and all mRNA-negative cases; combining the 3 tests correctly identified all cases. While no stand-alone test was sufficiently accurate for classifying HPV-associated OPSCC, the high sensitivity and specificity of the established combination of p16 immunostain, DNA ISH, and HPV16 DNA amplification suggests that the introduction of labour- and cost-intensive mRNA ISH, is not necessary in the diagnostic routine of oropharyngeal tumors.

Summary Background The aim of this study is to investigate if therapeutic weight loss reduces P wave dispersion. Methods 20 obese patients (10 males and 10 females), part of a randomized clinical trial, were examined over a 6 month period. They were treated with a diet, aiming at 5% weight loss at the 6th month. After physical examination, they underwent laboratory tests, bioelectrical impedance analysis and a electrocardiogram (ECG). ECGs were transferred to a personal computer via a scanner and then magnified 400 times. We examined at baseline and at the 6th month, maximum and minimum P-wave duration, P-wave dispersion and heart rate. Results Comparing responders (patients who lost 5% of weight at t6) and not responders (who lost less than 5%), responders showed a significant reduction of P wave dispersion value (−0.38 [SD: 0.35] mm equal to −32.3 [SD: 11.3] % p = 0.00001). All responders present a reduction of P wave dispersion, while for not-responders this is no longer evident. Finally, a good degree of correlation (r = 0.54) between P wave dispersion difference and the decrease of weight was noticed. Females have a better response in P dispersion reduction strictly connected with their weight loss with a good correlation, (r = 0.7, p = 0.002), versus a moderate correlation evidenced in males (r = 0.5, p = 0.011). Conclusion P wave duration and dispersion are significantly reduced in patients who lost more than 5% of weight and this decrease is highly related to the extent of weight loss.

Summary Background and aims The beneficial effect of cognitive therapy was found particularly in eating disorders, but, to date, it has rarely been studied in obese patients without eating disorders. The aim of this pragmatic randomized clinical trial was to evaluate the effectiveness of a novel brief group cognitive behavioral treatment (CBT), accepted and performed in clinical practice, in addition to a prescriptive diet with respect to the prescriptive diet alone (standard care), in obese and overweight outpatients without eating disorders. Methods One hundred sixty three patients [44 men and 119 women; 45 ± 11 yr; mean body mass index (BMI) of 32 ± 4 kg/m2] aged 18–65 years who were from overweight (BMI between 25 and 29.9) to 2° class obese (BMI between 35 and 39.9 kg/m2) were followed for 12 months in a public obesity ambulatory. The study was based on a nutritional intervention lasting for six months. Weight loss was obtained with a hypo caloric balanced diet. Standard care consisted in a low-calorie diet, and a control visit every three months. Group CBT patients received the same diet but in addition they attended a series of seven subsequent meetings divided in small groups. Primary outcome is defined as the percentage of patients in each group achieving a 10% reduction of body weight at 12 months in comparison with baseline value. After randomization, at baseline patients underwent laboratory tests, bioelectrical impedance analysis, ECG and psychometric tests, and they were followed-up at six and 12 months. Results The average weight loss obtained at six and 12 months was respectively 6.0% and 7.44% for all patients, and this is in accordance with other similar studies. The primary outcome has been reached by 19 patients (24%) out of 78 who concluded the follow-up. Considering an ITT univariate analysis, the primary outcome was independent from treatment arm (OR .854, CI .39–1.871, p = 0.633) and the two treatments were substantially similar. Metabolic parameters (glucose levels, lipid profile, blood pressure), as expected, ameliorated in both groups during follow-up. The only independent predictor of successful weight loss was baseline glucose levels (OR 1.05, CI 1.009–1.09, p = 0.04), thus representing a higher risk of disease perceived by patients. Conclusion A brief group CBT, when added to standard care, was not superior to standard care alone in obese patients. The peculiar course of CBT planned only in the first six months, as well as the absence of a pure cognitive analysis may have impacted on the CBT success lower than expected. Further studies are needed in order to determine if longer intervention may be effective and feasible in a real-life primary care setting. Clinical trials registration Clinical trial.gov (n° NCT01686854 ).

Background & Aims A substantial proportion of patients with chronic hepatitis C virus infection treated with pegylated interferon α/ribavirin fail to achieve sustained virological response (SVR). Since growing evidence suggests that innate immunity may influence treatment responses, we examined natural killer (NK) cell phenotypic and functional changes during standard antiviral therapy. Methods Expression of several NK-cell regulatory molecules was evaluated by flow cytometry in 37 consecutive patients with chronic HCV infection at baseline and at different time points during and after discontinuation of treatment. Cytokine production was evaluated by intracellular staining. Cytolytic potential was assessed as degranulation and as antibody-dependent cytotoxicity. Results Baseline frequencies of CD56 dim NK cells and perforin content were significantly higher, whereas CD16 expression was lower in SVR vs. non-responder subjects. Analysis by linear regression for repeated measures during the first 12weeks showed significantly increased frequencies of activated (CD69 + ) NK cells in rapid virological responders (RVR) and identified a typical NK cell profile associated with SVR, featuring higher NK perforin content, lower CD16 expression, and higher proportion of CD56 dim /CD16 − cells. Moreover, SVR patients displayed higher natural and antibody-dependent NK cell cytotoxicity. IL28B rs12979860 CC homozygosis was significantly associated with SVR, independently of NK-cell phenotype and function. Conclusions Different NK-cell phenotypic and functional features, in patients with chronic hepatitis C treated with standard therapy, were observed between non-responder vs. SVR patients, suggesting a potential role of NK cells in the response to treatment.

To assess pregnancy-associated plasma protein A (PAPP-A) correlation with GDM and its usefulness in predicting GDM in primiparous women.First trimester data related to 307 pregnant women affected by GDM and 366 control pregnant women were retrieved from a computer data base and integrated with ad hoc data. Clinical data were recorded at delivery. A logistic model was used to analyze the association between first trimester data and subsequent clinical outcomes. We derived a risk score using both classical risk factors for GDM and PAPP-A.Diabetic and control women were significantly different in terms of age (p0.001), BMI (p0.001), weight (p0.001), family history of diabetes (p0.001), PAPP-A concentration and PAPP-A corrected multiple of the median (MoM) (p0.001). The ROC-AUC of the clinical risk score was 0.60 (95%CI 0.56-0.64), the adjusted score including PAPP-A MoM was 0.70 (95%CI 0.66-0.74).Low PAPP-A was strongly associated with GDM and lower values were found in diabetic women needing insulin therapy. Adding PAPP-A to first trimester screening could improve the prediction of women at high risk who will develop GDM. Further studies are needed to validate the applicability of our findings in different populations and settings.

Objective To evaluate short-term neurodevelopmental outcome (at 24 months of corrected age) and correlations with obstetric and neonatal factors in a sample of preterm very low birth weight infants born and admitted to an Italian tertiary centre between 2005 and 2007. Methods 156 infants with a birth weight ≤ 1500 g (gestational age, range: 27–31 weeks) were followed at regular intervals through neurodevelopmental (neurological and psychomotor) assessment up to 24 months of corrected age. A statistical analysis was conducted in order to look for correlations between pre- and perinatal variables and neuropsychomotor outcome at 24 months. Results 131 children were classified as normal and the other 25 presented sequelae classified as “minor” in 17 cases and as “major” in eight. The most significant risk factors for a poor outcome were preterm premature rupture of the membranes, bronchodysplasia, late-onset sepsis, postnatal steroid therapy and male gender. The presence of severe abnormalities on brain ultrasound scan and of an abnormal neurological assessment at 40 weeks at term equivalent age were strong predictors of poor outcome. Conclusions Our study is one of the few investigating the short-term outcome of preterm VLBW Italian children born in the second half of the 2000s. Neurodevelopmental assessment at 24 months revealed a marked reduction in major sequelae. Several risk factors for a poor neurodevelopmental outcome identified in children born in earlier periods were confirmed in these children born in recent years.

Objective To evaluate the reproducibility of real-time shear wave elastography in assessing liver elasticity in healthy volunteers. Methods Forty-two volunteers were studied in day 1. Shear wave elastography studies were performed by using the ultrasound system Aixplorer™ (SuperSonic Imagine S.A., Aix-en-Provence, France) with a convex broadband probe. Measurements were carried by two operators, an expert (operator 1) and a novice (operator 2). Examinations were performed on the right lobe of the liver. Each operator performed 10 consecutive measurements in each volunteer. In a subset of volunteers (n = 18) measurements were performed twice on two different days (day 1 and day 2). Intraobserver and interobserver agreement were assessed by intraclass correlation coefficient. Results Intraobserver agreement between measurements performed in the same subject in the same day (day 1 or day 2) showed intraclass correlation coefficient values of 0.95 (95% confidence interval, 0.93–0.98) and 0.93 (95% confidence interval, 0.90–0.96) for operator 1 and operator 2, respectively. Intraobserver agreement between measurements performed in the same subject in different days showed intraclass correlation coefficient values of 0.84 (95% confidence interval, 0.69–0.98) and 0.65 (95% confidence interval, 0.39–0.91) for operator 1 and operator 2, respectively. Interobserver agreement was 0.88 (95% confidence interval, 0.82–0.94). Conclusions The results of this study show that shear wave elastography is a reliable and reproducible noninvasive method for the assessment of liver elasticity. Expert operator had higher reproducibility of measurements over time than novice operator.

Background Rapid on-site evaluation (ROSE) of transbronchial needle aspirates has long been used during flexible bronchoscopy, but its usefulness in the diagnosis of hilar and mediastinal adenopathy is controversial. The aim of the present study was to evaluate the extent to which ROSE can be valuable in patients undergoing transbronchial needle aspiration (TBNA) for the diagnosis of hilar and mediastinal adenopathy. Methods A total of 168 consecutive patients with enlarged lymph nodes were randomized to undergo TBNA with or without ROSE. The primary outcome measure of the study was the diagnostic yield of TBNA on a per-patient basis. Secondary outcome measures included the percentage of adequate specimens on a per-lymph node basis, the number of biopsy sites on a per-patient basis, and the complication rate of bronchoscopy on a per-patient basis. Results We found no significant difference between the TBNA group and the ROSE group in terms of diagnostic yield (75.3% vs 78.3%, respectively; P = .64), and percentage of adequate specimens (86.5% vs 78.4%, respectively; P = .11). The median (interquartile range) number of biopsy sites was significantly lower in the ROSE group (1 [1-2] vs 2 [1-2], respectively; P = .0005). The complication rate of bronchoscopy was significantly lower in patients undergoing on-site review (6% vs 20%; P = .01), whereas the complication rate of TBNA was similar among the study groups. Conclusions ROSE of transbronchial aspirates from hilar and mediastinal nodes enables avoidance of additional biopsy without loss in diagnostic yield and reduces the complication rate of bronchoscopy. Trial registry ClinicalTrials.gov; No.: NCT00915330; URL: www.clinicaltrials.gov

To evaluate and compare cardiovascular adaptation of 36 preterm and 34 fullterm newborns, we analyzed BNP concentration and echocardiographic parameters at day 3 of life and at day 28 (+/-2). On day 3 BNP concentrations (pg/ml) resulted higher in PDA preterm group (n=11; 125, IQR 56.1-301) than preterm without PDA (n=25; 25.5 IQR 10.9-49; p

Endophenotypes are simple biological aspects of a disease that can be observed in unaffected relatives at a higher rate than in the general population; an "autism endophenotype" justifies the observation that a mild reduction in ideational fluency and nonverbal generativity might be observed in healthy, unaffected relatives of children with autism. Because it is becoming apparent that autism is associated with given alleles encoding within the human leukocyte antigens region, a region of pivotal importance in immunity, we examined whether the "autism endophenotype" would extend its effects on the immune system.Multiple immune parameters were analyzed in autistic children (AC) (n = 20), their siblings (HSAC) (n = 15), and age- and gender-comparable healthy control subjects (HC) (n = 20) without any familiarity for autism.The immune profiles of HSAC were significantly more similar to those of their autistic siblings than to what was observed in HC. Thus, in AC and HSAC compared with HC: 1) proinflammatory and interleukin-10-producing immune cells were augmented (p.01 in both comparisons); 2) CD8(+) naïve (CD45RA(+)/CCR7+) T lymphocytes were increased (p.0001 and p = .001); and 3) CD8(+) effector memory (CD45RA(-)/CCR7-) (p.0001 and p = .03) as well as CD4(+) terminally differentiated (CD45RA(-)/CCR7+) (p.05 in both comparisons) lymphocytes were diminished. Serum autoantibodies (GM1) could be detected in 10% of AC children alone.Results of this pilot study indicate that a complex immune dysfunction is present both in autistic children and in their non-autistic siblings and show the presence of an "autism endophenotype" that expands its effects on immunologic functions.

Graft re-infection invariably occurs after liver transplantation (OLT) for chronic hepatitis C and disease progression is unpredictable. We prospectively examined peripheral blood mononuclear cells (PBMC) subsets and natural killer (NK) cell receptors (NKRs) in patients with recurrent hepatitis C post-OLT.PBMC were obtained at baseline and at different time points after OLT. NKRs were identified using monoclonal antibodies by flow cytometry.The proportions of NK, natural T (NT), total and gammadelta T cells were significantly reduced (p0.01) 7 days post-transplant, probably as a result of graft repopulation. NKG2D+ NK cells were significantly higher compared with healthy controls (p0.01), declined post-OLT and subsequently returned to baseline values. This, together with a progressive increase in the proportion of CD94/NKG2C+ NK cells over time (por = 0.01), appeared to be related to hepatitis C recurrence. There was a statistically significant correlation between expression of the natural cytotoxicity receptors (NCRs) and ALT (p0.05), supporting the hypothesis that NK cells participate in the necroinflammatory process.The data are compatible with homing of immune cells to the liver allograft after surgery, most of which return to pre-OLT levels. HCV recurrence may cause variations in selected NKRs expression akin to other viral infections.

We evaluated the correlation between brain natriuretic peptide (BNP) in umbilical cord blood after normal pregnancy, in blood samples of twenty-nine Italian healthy newborns and paired echocardiographic parameters. Plasma BNP was evaluated in UCB (T0) and in blood on day 3 (T1), 30 (T2) of life. Echocardiographic parameters were recorded at T1 and T2. Median of BNP concentrations in cord blood was 8.6 pg/ml. Median BNP concentrations on T1 was 59.2 pg/ml, on T2 was 8.7 pg/ml. Significantly higher BNP concentrations were reported on T1 than T0 and T2 (p0.0001), while no significant difference resulted between T0 and T2. Plasma BNP at T2 was significantly correlated with mVTI (p=0.006), E wave (p=0.004), LA (p=0.047), LVPW (p=0.004), M (p=0.025). No correlation was found with SF% and E/A. Our results confirm that in healthy and term neonates the cord blood BNP concentrations are low. On T1 BNP values are high with wide ranges because of physiological adjustment to postnatal circulation. When echocardiographic parameters are in normal ranges, BNP concentrations return to low levels on day 30. In healthy newborns left ventricular filling, LA size and M seem to influence BNP levels rather than left ventricular systolic and diastolic function.

Data regarding the efficacy of programmes to control meticillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs) are limited. We performed an observational 'before-and-after' study to evaluate the search-and-destroy (SD) strategy as compared with SD and isolation (SDI), to control MRSA in a general ICU. SD included active surveillance, contact precautions and treatment of carriers; in SDI, isolation or cohorting were added. Three phases were identified: period 1 (p1), 1996-1997, before the introduction of programme; period 2 (p2), 1998-2002, with SD programme; period 3 (p3), 2003-2005, with SDI in a new ICU. During the 10 years of the study we observed 3978 patients; 667, 1995 and 1316 patients in p1, p2 and p3 respectively. The numbers of MRSA-infected patients were 19 in p1, 23 in p2, and 6 in p3. The infection rate was 3.5, 1.7 and 0.7 cases per 1000 patient-days in p1, p2 and p3, respectively; a significant reduction was observed between p1 vs p2 (P=0.024) and p2 vs p3 (P=0.048), although the latter was not confirmed by a segmented regression analysis. The proportion of ICU-acquired MRSA cases was 80%, 77% and 52% during p1, p2 and p3, respectively (P=0.0001 for trend). The proportion of S. aureus isolates resistant to meticillin was 51%, 32% and 23% during p1, p2 and p3, respectively (P0.0001 for trend). SD strategy was effective in significantly reducing MRSA infection, transmission rates and proportion of meticillin resistance in an ICU with endemic MRSA. SDI may further enhance SD efficacy.

To investigate the signs of inflammatory processes in Alzheimer's disease (AD), we examined peripheral blood mononuclear cells (PBMC) from 51 AD patients (29 with mild and 22 with moderately severe dementia) and 51 age-matched healthy controls (HC), using flow cytometry to analyse the absolute number and the percentage of T, B and NK cells. We also studied the surface expression of CD25, CD28, CD57, CD71, CD45RA and CD45RO markers on cells CD4+ and CD8+. In 30 AD patients and 20 HC the production of IL-2, IFN-gamma, IL-10 and TNF-alpha by PBMC after stimulation with [25-35], [1-40] and [1-16] beta-amyloid (betaA) fragments was also evaluated. A significant decrease in circulating B and CD8+CD28- cells, as well as an increase in CD8+ cells expressing CD71+ and CD28+, was observed in AD patients. A significant decrease in IL-10 production was also found after stimulation of PMBC with betaA [1-40]. The decreased IL-10 production was not related to disease severity. The observed imbalance of immune peripheral cell subpopulations and decreased IL-10 production point to a reduction of suppressor cell function in AD patients.

Objective: To determine the impact of genotypic inhibitory quotient (GIQ) for lopinavir (LPV) in patients failing HAART with limited antiretroviral exposure. Design: Retrospective analysis of a prospective trial. Methods: Lopinavir GIQ was calculated as the ratio between the mean trough concentration (Ctrough) and the number of protease mutations using eight different HIV drug resistance mutation lists or algorithms. Early (by week 12) and confirmed (up to week 24) virological response (HIV-RNA < 400 copies/mL, ECVR) was used as dependent variable in logistic regression model. Results: Seventy-one of 109 (65%) patients achieved ECVR. At multivariable logistic regression analysis, each μg/mL increase of GIQ was correlated with increasing probability of ECVR as far as the following mutations were computed: multi-protease inhibitor (PI) associated mutations listed by IAS (OR = 1.17; 95% CI = 0.99-1.39; P = 0.058), mutations associated with LPV resistance by ANRS algorithm (OR = 1.21; 95% CI = 1.02-1.44; P = 0.03), major mutations associated with LPV resistance by Stanford database (OR = 1.16; 95% CI = 1-1.35; P = 0.05), and the whole set of mutations associated with LPV resistance in the same database (OR = 1.22; 95% CI = 1.02-1.46; P = 0.03). Using ROC curve method, a specific threshold GIQ was assessed, above which this parameter could predict ECVR with the highest sensitivity (74.6% with GIQ obtained through Stanford LPV mutations) or specificity (89.5% with GIQ obtained through ANRS LPV mutations). Conclusions: Our results suggest that increasing GIQ can improve virological outcome even in patients with limited exposure to PIs. Further studies are necessary to understand what HIV protease mutations should be considered and whether such mutations should be weighted differently to improve LPV GIQ predictive value. © 2005 Elsevier B.V. All rights reserved.

Matrix metalloproteinases (MMPs) 2 and 9 are responsible for extracellular matrix breakdown and their abnormal circulating levels may pre-date clinical evidence of diabetic angiopathy. We detected by ELISA, plasma MMP-2 and MMP-9 levels and associated activity in 25 children and adolescents with T1DM. Thirteen male and 12 female patients were evaluated at the clinical diagnosis and onset of T1DM and again at a 5-year follow-up. Twelve patients had developed microangiopathic complications at the follow-up evaluation. MMP-2 and MMP-9 levels and activity were detected in samples obtained at T1DM diagnosis and at the 5-year follow-up. As controls, 19 healthy subjects who were the same age as the patients were also evaluated at baseline and again after 5 years. MMP-2 levels and activity were significantly higher in the patients than in the controls at disease onset. This was particularly evident when patients who developed microangiopathic complications were compared to controls and patients without complications. At the 5-year follow-up, a significant increase in MMP-2 levels and a significant decrease in MMP-2 activity were found only in the control group compared to the baseline levels. MMP-2 levels and activity were higher in patients with microangiopathy. MMP-9 levels and activity were increased in all groups compared to baseline levels. MMP-9 levels were lower in patients with microangiopathy compared to controls, but no difference was found between the two patient groups. It is well known that MMP-9 is an index of the severity and stability of macroangiopathy while our results allow us to postulate that MMP-2 may be a marker of microangiopathy.

But de l’etude Comparer les potentiels evoques visuels par flash (fPEV) et pattern, aussi bien transitoires (pPEV-t) qu’en « steady state » (pPEV-ss), de nouveau-nes prematures avec ceux de nouveau-nes a terme et sains. Materiel et methodes Nous avons examine 29 enfants prematures (28-35 semaines d’âge gestationnel) et enregistre les fPEV, les pPEV-t et les pPEV-ss a diverses frequences spatiales, a l’âge de trois mois post-natal, a trois mois d’âge corrige, a huit mois d’âge post-natal et d’âge corrige. Nous avons compare ces resultats avec ceux obtenus en examinant 92 bebes a terme a l’âge de 3 et 8 mois. Resultats En ce qui concerne le pPEV-ss, les frequences spatiales percues etaient de 2 C/d dans le groupe de 3 mois d’âge post-natal, > 2 C/d dans le groupe de 3 mois d’âge corrige et de 3 mois a terme. Dans le groupe de 8 mois d’âge post-natal et de 8 mois a terme, elles etaient superieures a 5 C/d. Les latences des fPEV (onde P1) et des pPEV-t (onde P100) etaient de 192 ms et 207,9 ms respectivement, a l’âge de 3 mois post-natal ; de 144 ms et 137,7 ms a 3 mois d’âge corrige ; de 126,3 ms et 124,1 ms a 8 mois d’âge post-natal ; de 112,7 ms et 112,5 ms a 8 mois d’âge corrige ; de 137,3 ms et 110,1 ms a 3 mois a terme ; de 122,3 ms et 100,5 ms a 8 mois a terme. Discussion Dans le groupe des prematures de 3 mois d’âge corrige, les latences du fPEV sont semblables a celles des nouveau-nes a terme ; celles du pPEV-t sont retardees a 3 et 8 mois. En ce qui concerne le fPEV, les latences sont meilleures chez les prematures de 8 mois d’âge corrige que chez les nouveau-nes a terme. Une meilleure performance par rapport aux nouveau-nes nes a terme a ete relevee chez les sujets de 8 mois d’âge corrige pour la stimulation pPEV-ss. Conclusion A 8 mois d’âge corrige, les prematures recuperent la difference relative au fPEV et au pPEV-ss, mais non celle relative au pPEV-t. Les differentes reponses correspondant aux differents types de potentiels evoques visuels utilises suggerent que des voies semblables se developpent en temps legerement differents.

Endomyocardial biopsy (EMB) is currently the standard method to diagnose acute graft rejection. However, considering the potential complications of this procedure, a noninvasive marker of rejection would be an ideal alternative or at least a helpful adjunct to posttransplant management. We measured myoglobin (Myo), creatine kinase MB mass (CK-MBm), troponin T (cTnT), serum amyloid A (SAA), and C-reactive protein (CRP) in 57 patients (mean age 37.5 years) who underwent orthotopic heart transplantation for end-stage cardiac failure between January and December 2001. Endomyocardial biopsies were performed routinely after surgery and histologically diagnosed rejection was graded according to the criteria of the International Society of Heart and Lung Transplantation. Concomittant with the biopsies, blood samples were drawn from the coronary sinus (central blood samples) and from a peripheral vein (peripheral blood samples) to assay biochemical markers. Among 149 EMB evaluated, 87 were negative (grade 0); 28 showed grade 1a rejection; 26 showed grade 1b; and 8 showed grade > 1b (2 were grade 2, 6 were grade 3a). Grades 0 and 1a were considered to be negative, while grades 1b and >1b were considered positive indicating potential acute graft rejection. cTnT, Myo, CK-MBm, SAA, and CRP levels were measured in 149 central blood samples and 149 peripheral blood samples. Myo and CK-MBm did not show significant changes. cTnT seems to be a potentially useful addition to the EMB results, while SAA and CRP showed variations with respect to EMB grade both in central and peripheral samples.

Study objectives: Transbronchial lung biopsy (TBLB) during flexible bronchoscopy (FB) is the recommended procedure for diagnosing sarcoidosis in most cases, although its yield in stage I disease is reported to be not as high as when parenchymal involvement is radiologically evident. We undertook this study to assess the diagnostic value of transbronchial needle aspiration (TBNA) in sarcoidosis presenting with hilar and/or mediastinal lymphadenopathy (stage I). Design: Retrospective review of bronchoscopy procedures performed over a 6-year period for the diagnostic workup of hilar and/or mediastinal lymphadenopathy, as detected by chest radiographs. Setting: Urban academic hospital. Patients: Fifty-five patients with hilar and/or mediastinal lymphadenopathy without pulmonary abnormalities were included in the analysis. Interventions: After chest CT and physical examinations, all patients underwent FB with TBNA. Patients thought to have clinicoradiologic findings highly consistent with sarcoidosis, as assessed by the bronchoscopists performing the procedures, underwent combined TBNA and TBLB. Results: A diagnosis of sarcoidosis was established in 32 patients. In the remaining 23 patients, other diseases were pathologically diagnosed. Overall, TBNA was diagnostic in 23 of 32 patients with sarcoidosis (72%) by showing nonnecrotizing granulomas in 28 of 39 lymph node stations sampled (72%). Among the 15 patients who were submitted to both TBNA and TBLB, TBNA exclusively established the diagnosis in 7 of 15 patients (47% increase in the diagnostic rate) and its yield exceeded that of TBLB (11 of 15 patients [73%] vs 6 of 15 patients [40%], respectively). The association of TBNA and TBLB increased the diagnostic yield to 87%. Conclusions: TBNA may be of great value in the diagnostic evaluation of patients with suspected stage I sarcoidosis, and its use in association with TBLB should be strongly encouraged. TBNA may also preclude the need for further surgical diagnostic procedures in several patients with hilar and/or mediastinal adenopathy due to causes other than sarcoidosis. (CHEST 2003; 124:2126 –2130)

In this study we evaluated whether a good response to conventional chemotherapy, i.e. a significant tumour reduction, is a prerequisite for improved survival in multiple myeloma (MM). Between January 1987 and March 1990, 341 consecutive previously untreated patients with MM received chemotherapy within the prospective, multicentre, randomised Protocol MM87. Of these, 258 patients were evaluable for both response and long-term survival and 244 (94.6%) have died. The median survival of all patients was 40 months (6–162 months). The median survival did not differ between patients who had complete response (CR) (50 months (9–162 months)), partial response (PR) (46 months (8–147 months)) or stable disease (SD) (41 months (7–135 months)). The median survival was shorter (13.6 months (6–135 months)) (P

Study objectives To evaluate early and late lung function abnormalities and their predictors in a large sample of children who underwent bone marrow transplantation (BMT) for leukemias in the 1990s, highlighting changes with respect to the 1980s. Designs Prospective cohort. Setting A university department of pediatrics. Participants Seventy-five consecutive children who underwent BMT were enrolled in the study (median age, 11 years; range, 6 to 19 years; 45 male and 30 female children). Twenty-three children received autologous BMT, and 52 children received allogeneic BMT; 50 children completed the study. Measurements Clinical examinations and lung function tests were performed before BMT, and 3 to 6 months, 12 months, and 24 months after BMT. Results Before BMT, at 3 to 6 months after BMT, and at 24 months after BMT, 44%, 85%, and 62% of children, respectively, had altered lung function in the absence of persistent respiratory symptoms. Between 3 months and 6 months after BMT, a restrictive pattern was the most frequent abnormality. The only predictive factors for late abnormalities were transplantation performed in the advanced disease phase (odds ratio [OR], 6.75; p = 0.005) and bronchopulmonary infections (OR, 3.9; p Conclusions These data suggest that a significant proportion of children who undergo BMT, especially if for leukemia in advanced phase, have early and late pulmonary abnormalities. These abnormalities, especially the late ones, seem to be more severe than patients reported in studies analyzing children undergoing BMT in the 1980s. This could be due to the more intensive front-line treatment protocols employed for treatment of children with acute leukemia in the 1990s.

The aim of the study was to investigate the in vitro T-cell response to recombinant hepatitis B (rHBsAg) in a group of children (defined as "slow responders") vaccinated at birth, presenting antibody levels < 10 mIU/ml after the vaccination schedule, and developing anti-rHBs antibodies after revaccination. T-cell mediated immune response towards rHBsAg was evaluated in 35 healthy children in "bulk" culture experiments (19 responders and 16 slow responders) and by limiting dilution analysis (nine responders and five slow responders) to quantify the frequency of proliferating T lymphocyte-precursors (PTL-p). Before the booster dose, lymphocytes from slow responder children failed to proliferate to rHBsAg, while a normal proliferation was observed in all responders. A statistically significant difference in rHBsAg-specific PTLp frequencies was observed between the two groups. Among the slow responder group, a significant increase of PTLp was observed after the supplementary vaccine dose.Nevertheless, PTLp frequencies remained significantly lower than those measured in responders. These results suggest a role for follow-up of slow responder children over time, in order to perform booster vaccination when inadequate anti-HBs titre is present.

The aim of the present study was to evaluate the persistence of anti-hepatitis B protective levels in young patients with type 1 diabetes, successfully immunised with a recombinant hepatitis B vaccine. We re-evaluated, after a 4 year follow-up, 54 patients and 70 age and sex-matched healthy subjects. Protective antibodies levels were found in 50/54 (92%) patients and in 67/70 (96%) controls. Moreover, anti-HBs levels were similar in diabetic patients and controls (means of log-titre and (sd); 1.95 (0.88) and 2.18 (0.64) patients and controls, respectively; P=0.11). No cases of clinical hepatitis were reported and all patients and controls remained HBc negative. These data demonstrate the persistence of anti-HBs levels in children, adolescents and young patients with type 1 diabetes after recombinant hepatitis B vaccine showing evidence of longterm immunogenity and protective effect.

We evaluated the response to the recombinant Hepatitis B vaccine using an accelerated schedule versus the traditional schedule by studying the immunologic memory induced in 200 children with HBs-Ag negative mothers. At seroconversion, the traditional schedule presented a higher percentage of children with serum HBs-Ag concentrations over 100 mIU/ml than the accelerated schedule. After five years this difference was no longer statistically significant and children who presented anti-HBsAg concentrations below 10 mUI/ml received an additional booster dose which stimulated the antibody concentration to exceed 100 mIU/ml in all cases. Recombinant HBV vaccine induced better long term immunologic memory when it was administered earlier.

The aim of the present study was to identify the true extent of the non-responsiveness in infants born from HBsAg-negative mothers, vaccinated against Hepatitis B Virus (HBV) at birth. Sixty-four non- and low-responding infants, selected from an initial cohort of 2009, were given two additional doses of recombinant HBV vaccine between the tenth and the twelfth month of age. A parallel evaluation was conducted on the response to anti-rubella and anti-tetanus vaccine. Only two infants remained non-responders, whereas 68% of the non-responders and 94% of the low responders after the primary vaccination schedule developed antibody titres over 100 mIU ml−1. No significant relationship between the specific antibody level against HBV and against rubella or tetanus 1 month after vaccination was observed.

Background/Aims: Institutionalised psychiatric patients are at increased risk of developing chronic infection with hepatitis B virus (HBV). However, little information is available on transmission and epidemiology of hepatitis C virus (HCV) in this setting. The aim of this study was to identify potential risk factors of acquiring HCV infection in two large psychiatric institutions in northern Italy. Methods: We designed a case-control study using randomly selected controls from the same study database, consisting of a total of 1180 patients, in order to satisfy the principle that both cases and controls should be representative of the same base experience. A multiple regression logistic analysis was used to identify features that could predict exposure to HXV as evidenced by the presence of circulating anti-HCV antibodies. Results: Anti-HCV was detected in 79 patients (6.7%). The prevalence of viraemia and the distribution of genotypes were very similar to those found in subjects with chronic HCV infection drawn from the same geographical area. Multivariate analysis indicated that a diagnosis of psychosis and a history of trauma were statistically significant independent risk factors associated with a positive anti-HCV result (OR 2.615, 1.273—5.373 95% CI and OR 2.096, 1.133–3.877 95% CI, respectively). Conclusions: The findings of this large epidemiological study show for the first time that prolonged residence in psychiatric institutions does not entail per se a significant risk of acquiring HCV infection. Since transmission of HCV in this setting appears to occur predominantly via classical parenteral routes, simple prophylactic measures appear to be adequate to prevent infection.

Viral genotypes have been associated with different severity and outcome of hepatitis C virus (HCV)-related liver disease. The aim of this study was to determine whether HCV genotypes may influence the cirrhosis-related risk of the development of hepatocellular carcinoma (HCC).Three groups of patients were studied: 593 patients with chronic hepatitis, 166 patients with HCC and cirrhosis, and 219 patients with cirrhosis but without HCC. A cross-sectional study of frequency distribution and a case-control analysis were performed. HCV genotypes were detected according to Okamoto.HCV type 1b infection was more prevalent among patients with HCC compared with patients with cirrhosis but without HCC (P0.01) and chronic hepatitis (P0.001). Age, male sex, and HCV type 1b significantly influenced the risk of cancer in cirrhosis by univariate analysis. A pairwise comparison performed on 162 patients with HCC and an equal number of patients with cirrhosis matched by age, sex, and Child's class showed that HCV type 1b was independently associated with HCC (odds ratio, 1.7; P = 0.026).HCV type 1b is overrepresented in patients with cirrhosis and HCC and significantly influences the risk of HCC in cirrhosis, independent of sex, age, and Child's class.

Background/Aims: The clinico-pathologic features of hepatitis C virus infection intravenous drug users are different from those found in other hepatitis C virus-infected patients. Our airm was to test whether specific viral variants circulate within this particular patient population. Methods: We studied the distribution of hepatitis C virus genotypes in 90 drug addicts and 484 controls, according to the method described by Okamoto. Results: Hepatitis C virus type 1a and 3a infections were more frequent among intravenous drug users than in 125 age-matched controls (48.8% and 21.1% vs 17.6% and 11.2%), accounting for the majority of infections in intravenous drug users. Analysis of hepatitis C virus genotypes according to age showed that, in the general population, hepatitis C virus types 1a and 3a were more prevalent among patients younger than 40 years of age than in older individual (17.6% and 11.2% vs. 1.4% and 0.6%). Conclusions: These findings suggest that hepatitis C virus types 1a and 3a were recently introduced in Italy, presumably via needle-sharing among intravenous drug users, and from this reservoir they are extending to the general population, particularly among younger subjects.