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OBJECTIVE: Information on the long-term safety of electronic cigarettes (e-cig) is still limited. We report the results after six years of follow-up of the first observational study assessing e-cig long-term effectiveness and safety. PATIENTS AND METHODS: Participants were adults who smoked ≥1 tobacco cigarette/day (tobacco smokers); or used any type of e-cig inhaling ≥50 puffs weekly (e-cig users); or used both (dual users). Participants were contacted directly or by phone and/or internet interviews. Hospital discharge abstract data and carbon monoxide level tests were also used. RESULTS: Data were available for 228 e-cig users (all ex-smokers), 469 tobacco smokers, 215 dual users. A possibly smoking-related disease (PSRD) was recorded in 90 subjects (9.9%); 11 deceased (1.2%). No differences were observed across groups in PSRD rates, with minor changes in self-reported health. Among e-cig users, 64.0% remained tobacco abstinent. Dual users and tobacco smokers did not significantly differ in the rate of cessation of tobacco (38.6% vs. 33.9%, respectively) and all products (23.7% vs. 26.4%). A comparable decrease in daily cigarettes was also observed. 39.5% of the sample switched at least once (tobacco smokers: 15.1%; dual users: 83.3%). CONCLUSIONS: After six years, no evidence of harm reduction was found among e-cig or dual users. The complete switch to e-cig might support tobacco quitters remain abstinent, but the use of e-cig in addition to tobacco did not improve smoking cessation or reduction.

OBJECTIVE: More than a decade after e-cigarette (e-cig) market launch, limited information are available on their safety after 24 months of use. In 2013, we started the first observational study assessing e-cig long-term effectiveness and safety, directly comparing tobacco smokers and e-cig users. Here we report the results after four years of follow-up. PATIENTS AND METHODS: Adults (30-75 years) were included if: smokers of =1 tobacco cigarette/day (tobacco smokers); users of any type of e-cig inhaling =50 puffs weekly (e-cig users); users of both tobacco and e-cig (dual users). Data were collected by phone and/or internet, and carbon monoxide levels tested in 50% of those declaring tobacco abstinence. Main outcomes were: possibly smoking-related diseases (PSRD; validated through hospital discharge data or visit in 62.6% of the sample); 4-year tobacco abstinence; number of tobacco cigarettes/day. RESULTS: Data were available for 228 e-cig users (all ex-smokers), 471 tobacco smokers, 216 dual users. A PSRD was observed in 73 subjects (8.0%). No differences emerged across groups in PSRD rates, with negligible variations in self-reported health. Of e-cig users, 63.6% remained tobacco abstinent; dual users and tobacco smokers showed non-significantly different rates of tobacco (33.8% vs. 26.8%) and all-product (20.2% vs. 19.4%) cessation, and a similar decrease in cigarettes/day. Almost 40% of the sample switched at least once (tobacco smokers: 17.2%; dual users: 81.9%). CONCLUSIONS: After four years, a scarce, non-significant harm reduction was observed among e-cig or dual users. Given the long-lasting health effects of tobacco smoking, the benefits of e-cig use may start being detectable at the next follow-up (six years). The complete switch to e-cig may help tobacco quitters remain abstinent, but e-cig use in addition to tobacco did not increase the likelihood of smoking cessation or reduction.

Diagnosis of isolated posterior fossa anomalies in children is biased by the fact that only those that are symptomatic are brought to the attention of the appropriate clinical personnel, and the reported rate is often affected by the adoption of different nomenclature, diagnostic criteria, outcome measures, duration of follow-up and neurodevelopmental tools. The aim of this systematic review was to explore the neurodevelopmental outcome of fetuses with a prenatal diagnosis of isolated posterior fossa anomalies.MEDLINE and EMBASE were searched electronically, utilizing combinations of the relevant medical subject heading terms for 'posterior fossa' and 'outcome'. Studies assessing the neurodevelopmental outcome in children with a prenatal diagnosis of isolated posterior fossa malformations were considered eligible. The posterior fossa anomalies analyzed included Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC) and vermian hypoplasia (VH). Two authors reviewed all abstracts independently. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. Meta-analyses of proportions were used to combine data, and between-study heterogeneity was explored using the I(2) statistic.A total of 1640 articles were identified; 95 were assessed for eligibility and a total of 16 studies were included in the systematic review. The overall rate of abnormal neurodevelopmental outcome in children with a prenatal diagnosis of DWM was 58.2% (95% CI, 21.8-90.0%) and varied from 0-100%. In those with a prenatal diagnosis of MCM, the rate of abnormal neurodevelopmental outcome was 13.8% (95% CI, 7.3-21.9%), with a range of 0-50%. There was no significant association between BPC and the occurrence of abnormal neurodevelopmental delay, with a rate of 4.7% (95% CI, 0.7-12.1%) and range of 0-5%. Although affected by the very small number of studies, there was a non-significant occurrence of abnormal neurodevelopmental delay in children with a prenatal diagnosis of VH, with a rate of 30.7% (95% CI, 0.6-79.1%) and range of 0-100%.Fetuses diagnosed with isolated DWM are at high risk of abnormal neurodevelopmental outcome, while isolated MCM or BPC have a generally favorable outcome. The risk of abnormal developmental delay in cases with isolated VH needs to be further assessed. In view of the wide heterogeneity in study design, time of follow-up, neurodevelopmental tests used and the very small number of included cases, further future large prospective studies with standardized and objective protocols for diagnosis and follow-up are needed in order to ascertain the rate of abnormal neurodevelopmental outcome in children with isolated posterior fossa anomalies. Copyright © 2015 ISUOG. Published by John WileySons Ltd.

To explore the outcome of fetuses with a prenatal diagnosis of ovarian cyst.The electronic databases MEDLINE and EMBASE were searched using keywords and word variants for 'ovarian cysts', 'ultrasound' and 'outcome'. The following outcomes in fetuses with a prenatal diagnosis of ovarian cyst were explored: resolution of the cyst, change of ultrasound pattern of the cyst, occurrence of ovarian torsion and intracystic hemorrhage, need for postnatal surgery, need for oophorectomy, accuracy of prenatal ultrasound examination in correctly identifying ovarian cyst, type of ovarian cyst at histopathological analysis and intrauterine treatment. Meta-analyses using individual data random-effects logistic regression and meta-analyses of proportions were performed. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale.Thirty-four studies (954 fetuses) were included. In 53.8% (95% CI, 46.0-61.5%) of cases for which resolution of the cyst was evaluated (784 fetuses), the cyst regressed either during pregnancy or after birth. The likelihood of resolution was significantly lower in complex vs simple cysts (odds ratio (OR), 0.15 (95% CI, 0.10-0.23)) and in cysts measuring ≥ 40 mm vs 40 mm (OR, 0.03 (95% CI, 0.01-0.06)). Change in ultrasound pattern of the cyst was associated with an increased risk of ovarian loss (surgical removal or autoamputation) (pooled proportion, 57.7% (95% CI, 42.9-71.8%)). The risk of ovarian torsion was significantly higher for cysts measuring ≥ 40 mm compared with 40 mm (OR, 30.8 (95% CI, 8.6-110.0)). The likelihood of having postnatal surgery was higher in patients with cysts ≥ 40 mm compared with 40 mm (OR, 64.4 (95% CI, 23.6-175.0)) and in complex compared with simple cysts, irrespective of cyst size (OR, 14.6 (95% CI, 8.5-24.8)). In cases undergoing prenatal aspiration of the cyst, rate of recurrence was 37.9% (95% CI, 14.8-64.3%), ovarian torsion and intracystic hemorrhage were diagnosed after birth in 10.8% (95% CI, 4.4-19.7%) and 12.8% (95% CI, 3.8-26.0%), respectively, and 21.8% (95% CI, 0.9-40.0%) had surgery after birth.Size and ultrasound appearance are the major determinants of perinatal outcome in fetuses with ovarian cysts. Copyright © 2016 ISUOG. Published by John WileySons Ltd.

Background Our study aimed to estimate the prevalence of pregnancy e-health seekers in a large Italian sample; to explore the factors influencing the choices of the childbearing women regarding their lifestyles after internet consultation; and finally to investigate potential differences between primiparous and multiparous women in internet use to find information about pregnancy. Methods A multicentre survey was carried out in seven Italian cities. Data were collected through a validated questionnaire administered in waiting rooms of outpatient departments by medical doctors. Respondents were questioned about their sociodemographic status, their use of the internet to seek pregnancy information and their consequent choices to modify their lifestyles. Data were analysed using descriptive statistics and logistic regression. Results Almost all women were pregnancy e-health seekers (95%), including those who also received information from healthcare professionals. Indeed, the main reason for searching the web was the need of further knowledge on pregnancy-related topic, over and beyond other key advantages of the net such as anonymity, simplicity and rapidity. A higher likelihood of changing lifestyle after pregnancy e-health was observed among the women who searched institutional websites; declared more confidence in the information retrieved; participated into pregnancy-centred forum online; and were residents in Italy. Conclusions To reduce the likelihood for women of both finding erroneous information or misinterpreting correct ones, healthcare professionals should commit to fill the information gap and guide pregnant women in the online searches. Also, future studies are strongly needed to analyse the quality and accuracy of health information found on the web.

Objective: To examine smoking prevalence, knowledge and attitudes, and tobacco cessation training among university students attending European medical schools using the Global Health Professional Students Survey approach. Methods: A cross-country, cross-sectional study was performed among 12 medical schools in four countries in Europe (Germany, Italy, Poland and Spain). The survey was performed during the second semester of the third year of study from March to May 2009. Results: In total, 2249 subjects entered the study (overall response rate 92%). The overall prevalence of smoking among medical students was 29.3% (95% confidence interval 28.1-34.7), with percentages ranging from 28% in Germany to 31.3% in Italy. This study found that more than two-thirds of medical students believe that health professionals are role models for patients, with different beliefs in Poland (89.6%) and Germany (77.7%) vs Italy and Spain (57.2% and 54.4%, respectively) (P < 0.001). Smoking cessation training at medical school was only reported by 16.5% of students (lowest proportion in Italy, 3.5%) (P < 0.001). In terms of smoking cessation methods, the vast majority (89.8%) of medical students were aware of nicotine patches and gum (highest prevalence in Spain, 96.3%), and 24.4% were aware of the use of antidepressants (highest prevalence in Germany, 33.6%). Conclusion: This European survey found that the prevalence of smoking was higher among medical students than the general population. There is a strong need to provide medical students with training in smoking cessation techniques

Background:There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families.Methods:This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community.Results:The societal burden of AD, composed of public, patient, and informal care costs, was about €20,000/yr. Out of this, the cost borne by the public sector was €4,534/yr. The main driver of public cost was the national cash-for-care allowance (€2,324/yr), followed by drug prescriptions (€1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at €13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure.Conclusion:The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (Trial Registration number: NCT01700556).

The accuracy of prenatal ultrasound examination in detecting jejunal and ileal atresia has been reported in the literature to be highly variable, at 25-90%. The aim of this systematic review was to evaluate the accuracy of prenatal ultrasound in detecting non-duodenal small bowel atresia (ND-SBA).MEDLINE, EMBASE and The Cochrane Library, including The Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and The Cochrane Central Register of Controlled Trials (CENTRAL), were searched electronically. The overall detection rate of jejunal or ileal atresia using ultrasound was reported. The accuracy of using polyhydramnios and dilated loops of bowel as diagnostic signs was also explored.Sixteen studies involving 640 fetuses were included in this review. The detection rate of ND-SBA by prenatal ultrasound was highly variable, with values ranging from 10 to 100%, with an overall prediction of 50.6% (95% CI, 38.0-63.2%). When analyzed separately, the detection rates of jejunal and ileal atresia were 66.3%, (95% CI, 33.9-91.8%) and 25.9% (95% CI, 4.0-58.0%), respectively. Both dilated loops of bowel and polyhydramnios as diagnostic signs for ND-SBA provided a low overall detection rate.The diagnostic performance of prenatal ultrasound in identifying ND-SBA is extremely variable. Large studies are needed in order to identify objective and combined criteria for the diagnosis of these anomalies.

The availability of family caregivers of older people is decreasing in Italy as the number of migrant care workers (MCWs) hired by families increases. There is little evidence on the influence of socioeconomic factors in the employment of MCWs.We analyzed baseline data from 438 older people with moderate Alzheimer's disease (AD), and their family caregivers enrolled in the Up-Tech trial. We used bivariate analysis and multilevel regressions to investigate the association between independent variables-education, social class, and the availability of a care allowance-and three outcomes-employment of a MCW, hours of care provided by the primary family caregiver, and by the family network (primary and other family caregivers).The availability of a care allowance and the educational level were independently associated with employing MCWs. A significant interaction between education and care allowance was found, suggesting that more educated families are more likely to spend the care allowance to hire a MCW.Socioeconomic inequalities negatively influenced access both to private care and to care allowance, leading disadvantaged families to directly provide more assistance to AD patients. Care allowance entitlement needs to be reformed in Italy and in countries with similar long-term care and migration systems.

It is well recognized that depression is independently associated with cardiovascular events. However, uncertainties remain on the pathophysiological pathways underlying the association between depression and coronary heart disease. In addition to the traditional cardiovascular risk factors, autonomic nervous system (ANS), low grade of inflammation, platelet and hypothalamic-pituitary-adrenal axis function and genetic factors may adversely impact the endothelium of the arterial wall. We provide an overview of the pathophysiological mechanisms and indices which seem to have a role in promoting and accelerating atherosclerosis and its complications due to plaque rupture and thrombosis. Given that the relationship between depression and atherosclerosis cannot be fully explained by single mechanisms, which seem at least partially interrelated, the depression-related dysfunctions in the ANS and hypothalamic-pituitary-adrenal axis seem to play a major role, promoting chronic inflammation, endothelial dysfunction and platelet activation and aggregation, which in turn are key steps in the development of atherosclerosis and its complications.

Background Young individuals are the age group with the highest risk of car accidents. One of main explanations relies on the use of psychoactive substances (alcohol, illegal and medicinal drugs), which are known to be major risk factors of road accidents, and whose consumption is almost universally more common among younger drivers. Although the correlation between psychoactive substances use and decrease in driving performance has been established in controlled experimental or laboratory settings, few studies were conducted in naturalistic circumstances. The TEND by Night project has been designed to evaluate the relationship between driving performance and psychoactive substances assumption in young drivers enrolled at typical places of consumption. Methods/Design The TEND by Night project, endorsed by the European Commission, is a multidisciplinary, multi-centric, cross-sectional study conducted in six European countries (Italy, Belgium/Netherlands, Bulgaria, Spain, Poland and Latvia). The study population consists of 5000 young drivers aged 16-34 years, attending recreational sites during weekend nights. The intervention is based on the portal survey technique and includes several steps at the entrance and exit of selected sites, including the administration of semi-structured questionnaires, breath alcohol test, several drug assumption test, and measurement of the reaction time using a driving simulator. The main outcome is the difference in reaction time between the entrance and exit of the recreation site, and its correlation with psychoactive substances use. As a secondary outcome it will be explored the relationship between reaction time difference and the amount of consumption of each substance. All analyses will be multivariate. Discussion The project methodology should provide some relevant advantages over traditional survey systems. The main strengths of the study include the large and multicentric sample, the objective measurement of substance assumption (which is typically self-reported), the application of a portal survey technique and the simultaneous evaluation of several psychoactive substances.

When treating HCV patients with conventional dual therapy in the current context of rapidly evolving HCV therapy, outcome prediction is crucial and HCV kinetics, as early as 48 hours after the start of treatment, may play a major role. We aimed at clarifying the role of HCV very early kinetics. We consecutively enrolled mono-infected HCV patients at 7 treatment sites in Central Italy and evaluated the predictive value of logarithmic decay of HCV RNA 48 hours after the start of dual therapy (Delta48). Among the 171 enrolled patients, 144 were evaluable for early and sustained virological response (EVR, SVR) prediction; 108 (75.0%) reached EVR and 84 (58.3%) reached SVR. Mean Delta 48 was 1.68 ± 1.22 log10 IU/ml, being higher in patients with SVR and EVR. Those genotype-1 patients experiencing a Delta 482 logs showed a very high chance of success (100% positive predictive value), even in the absence of rapid virological response (RVR). Evaluation of very early HCV kinetics helped identify a small but significant proportion of genotype-1 patients (close to 10%) in addition to those identified with RVR, who could be treated with dual therapy in spite of not reaching RVR. In the current European context, whereby sustainability of HCV therapy is a crucial issue, conventional dual therapy may still play a reasonable role in patients with good tolerance and early prediction of success.

A cross-sectional, multicenter study was carried out in 6 Italian cities (Cassino, Chieti, Naples, Rome, Siena, Turin) in order to highlight differences in Web use to find out health information and its related consequences on behavioral choices and to describe the distribution of the phenomenon in Italy. Data were collected from October 2009 to September 2010 on a sample of volunteers recruited from laboratory analysis, with face-to-face interview, including information about socio-demographic, health, and Web use to health. Data analysis shows that e-health use is greater in Northern Italy, in women aged 30-41 years, in chronic patients and those who have been caught up medical malpractice. Behavioral changes are associated with the Region; in particular Rome and Cassino show to choose/change professionals and facilities, engaging in alternative therapies and buy drugs online more frequently. Living in Southern Italy, a lower educational level and the infrequent drugs use are associated with a greater probability of incurring in negative behaviors. Positive results on the behavior are instead low and not significant. Given the regional differences, the potentiality and the risks of e-health use, it will be important to identify strategies for risks containment and implementation of the web in prevention.

Objective. To synthesize the determinants of gender inequalities through a narrative review that: (i) describes gender related var- iables that can create different levels of health; (ii) describes key points that may assist in policy development and its reorientation towards gender differences; (iii) debates potential approaches in understanding gender issues. Methods. Review of the international literature through online databases (Pubmed), search engines, publications and documents from ?grey literature?. Inclusion criteria: publications from 1997, English language; keywords used: gender based analysis; gender and public policy; women?s health; gender differences; health policy; gender impact assessment. Among the 300 papers retrieved, 55 were selected for relevance. Results. We performed a narrative synthesis of the included literature, regarding: (i) gender differences and their determi-nants; (ii) elements for the changing; (iii) possible approaches; (iv) gender influences the pursuit of health and health care access through specific variables; (v) health policies can modify these variables only by a minimal percentage. These interventions should guarantee equity and allow efficient resources allocation. The gap between political announce- ments and real policy implementation remains unchanged. (vi) Standard approaches to the topic are not feasible due to the scarcity of a specific literature and the numerous cultural differences. Conclusions. Gender analysis of policies suggests they can dif- ferently affect women in comparison to men. However, reforms, strategies and interventions introduced in the last two decades, have achieved a limited success towards better gender equality in health. The main aim is to attack the structural sources of gender inequity in the society., Journal of Preventive Medicine and Hygiene, Vol 50, No 1 (2009)

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8–0.9 per week increase; p Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

WOS:000613461600006 PubMed ID: 32926494 Objectives To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. Methods This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. Results In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251(27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. Conclusions SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. (C) 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Objective: To determine the role of progesterone, pessary and cervical cerclage in reducing the risk of (preterm birth) PTB in twin pregnancies and compare these interventions using pairwise and network meta-analysis. Study design: Medline, Embase, CINAHL and Cochrane databases were explored. The inclusion criteria were studies in which twin pregnancies were randomized to an intervention for the prevention of PTB (any type of progesterone, cervical cerclage, cervical pessary, or any combination of these) or to a control group (e.g. placebo or treatment as usual). Interventions of interest were either progesterone [vaginal or oral natural progesterone or intramuscular 17a-hydroxyprogesterone caproate (17-OHPC)], cerclage (McDonald or Shirodkar), or cervical pessary. The primary outcome was PTB < 34 weeks of gestation. Both primary and secondary outcomes were explored in an unselected population of twin pregnancies and in women at higher risk of PTB (defined as those with cervical length 0.05). When stratifying the analysis for spontaneous PTB, neither pessary, vaginal or intramuscular 17-OHPC were associated with a significant reduction in the risk of PTB compared to controls (all p > 0.05), while there was no study on cerclage which explored this outcome in an unselected population of twin pregnancies. When considering twin pregnancies with short cervical length (≤25 mm), there was no contribution of either pessary, vaginal progesterone, intra-muscular 17-OHPC or cerclage in reducing the risk of overall PTB < 34 weeks of gestation. Conclusions: Cervical pessary, progesterone and cerclage do not show a significant effect in reducing the rate of PTB or perinatal morbidity in twins, either when these interventions are applied to an unselected population of twins or in pregnancies with a short cervix.

Background Idiopathic Pulmonary Fibrosis (IPF) is an aggressive interstitial lung disease with an unpredictable course. Occupational dust exposure may contribute to IPF onset, but its impact on antifibrotic treatment and disease prognosis is still unknown. We evaluated clinical characteristics, respiratory function and prognostic predictors at diagnosis and at 12 month treatment of pirfenidone or nintedanib in IPF patients according to occupational dust exposure. Methods A total of 115 IPF patients were recruited. At diagnosis, we collected demographic, clinical characteristics, occupational history. Pulmonary function tests were performed and two prognostic indices [Gender, Age, Physiology (GAP) and Composite Physiologic Index (CPI)] calculated, both at diagnosis and after the 12 month treatment. The date of long-term oxygen therapy (LTOT) initiation was recorded during the entire follow-up (mean = 37.85, range 12–60 months). Results At baseline, patients exposed to occupational dust [≥ 10 years (n = 62)] showed a lower percentage of graduates (19.3% vs 54.7%; p = 0.04) and a higher percentage of asbestos exposure (46.8% vs 18.9%; p 0.002) than patients not exposed [

Objective: Specific comorbidities and old age create a greater vulnerability to severe Coronavirus Disease 19 (COVID-19). While obesity seems to aggravate the course of disease, the actual impact of the BMI and the cutoff which increases illness severity are still under investigation. The aim of the study was to analyze whether the BMI represented a risk factor for respiratory failure, admission to the intensive care unit (ICU) and death. Research design and methods: A retrospective cohort study of 482 consecutive COVID-19 patients hospitalised between March 1 and April 20, 2020. Logistic regression analysis and Cox proportion Hazard models including demographic characteristics and comorbidities were carried out to predict the endpoints within 30 days from the onset of symptoms. Results: Of 482 patients, 104 (21.6%) had a BMI ≥ 30 kg/m2. At logistic regression analysis, a BMI between 30 and 34.9 kg/m2 significantly increased the risk of respiratory failure (OR: 2.32; 95% CI: 1.31–4.09, P = 0.004) and admission to the ICU (OR: 4.96; 95% CI: 2.53–9.74, P 2 (OR: 12.1; 95% CI: 3.25–45.1, P Conclusions: Obesity is a strong, independent risk factor for respiratory failure, admission to the ICU and death among COVID-19 patients. A BMI ≥ 30 kg/m2 identifies a population of patients at high risk for severe illness, whereas a BMI ≥ 35 kg/m2 dramatically increases the risk of death.

Renal failure is a worldwide disease with a continuously increasing prevalence and involving a rising need for long-term treatment, mainly by haemodialysis. Arteriovenous fistula (AVF) is the favourite type of vascular access for haemodialysis; however, the lasting success of this therapy depends on its maturation, which is directly influenced by many concomitant processes such as vein wall thickening or inflammation. Understanding the molecular mechanisms that drive AVF maturation and failure can highlight new or combinatorial drugs for more personalized therapy. In this review we analysed the relevance of critical enzymes such as PI3K, AKT and mTOR in processes such as wall thickening remodelling, immune system activation and inflammation reduction. We focused on these enzymes due to their involvement in the modulation of numerous cellular activities such as proliferation, differentiation and motility, and their impairment is related to many diseases such as cancer, metabolic syndrome and neurodegenerative disorders. In addition, these enzymes are highly druggable targets, with several inhibitors already being used in patient treatment for cancer and with encouraging results for AVF. Finally, we delineate how these enzymes may be targeted to control specific aspects of AVF in an effort to propose a more specialized therapy with fewer side effects.

The aim of the present study was to evaluate the contamination levels of some classes of persistent organic pollutants in free-range hen eggs and to estimate the related human dietary exposure in a site of national interest, characterized by a serious state of environmental pollution in the Bussi sul Tirino area in central Italy. For these purposes, 17 samples of free-range hen eggs collected in home-producing farms located in the site of national interest territory were analyzed for 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), 12 dioxin-like polychlorinated biphenyls (dl-PCBs), and 6 non-dioxin-like PCBs (ndl-PCBs). Dietary exposure was assessed assuming a standard consumption of eggs per week. The concentration of ∑PCDD/Fs plus dl-PCBs ranged from 0.463 to 8.028 pg toxic equivalent g-1 fat, whereas the mean contamination level of the ∑ndl-PCBs ranged from 0.234 to 7.741 ng toxic equivalent g-1 fat. PCDD/Fs and PCBs contamination levels were lower than maximum values established by the Commission Regulation (European Union) 1259/2011, except for one sample. The estimated weekly intake, calculated to evaluate the contribution in terms of the monitored pollutants of the locally produced eggs to the diet, was lower than the tolerable weekly intake established by the European Food Safety Authority. HIGHLIGHTS

Objective: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography. Method: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (

Background: In Italy, a nationwide full lockdown was declared between March and May 2020 to hinder the novel coronavirus disease 2019 (COVID-19) pandemic. The potential individual health effects of long-term isolation are largely unknown. The current study investigated the arrhythmic consequences of the COVID-19 lockdown in patients with defibrillators (ICDs) living in the province of Ferrara, Italy. Methods: Both the arrhythmias and the delivered ICD therapies as notified by the devices were prospectively collected during the lockdown period (P1) and compared to those occurred during the 10weeks before the lockdown began (P2) and during the same period in 2019 (P3). Changes in outcome over the three study periods were evaluated for significance using McNemar's test. Results: A total of 413 patients were included in the analysis. No differences were found concerning either arrhythmias or shocks or anti-tachycardia pacing. Only the number of patients experiencing non-sustained ventricular tachycardias (NSVTs) during P1 significantly decreased as compared to P2 (p=0.026) and P3 (p=0.009). The subgroup analysis showed a significant decrease in NSVTs during P1 for men (vs. P2, p=0.014; vs. P3, p=0.040) and younger patients (vs. P2, p=0.002; vs. P3, p=0.040) and for ischemic etiology (vs. P2, p=0.003). No arrhythmic deaths occurred during P1. Conclusions: The complete nationwide lockdown, as declared by the Italian government during the first COVID-19 pandemic peak, did not impact on the incidence of arrhythmias in an urban cohort of patients with ICDs.

Objective To assess the effectiveness of an HPV vaccination programme in reducing the risk of cervical abnormalities identified at subsequent screening. Design Retrospective cohort study using administrative health data. Setting General population of Ferrara Province, Italy. Population Female residents born in 1986-1993 and participating in the organized cervical screening programme in 2011-2018, who were eligible for HPV vaccination in catch-up cohorts. Methods Logistic regression to evaluate the potential association between abnormal cervical cytology and one, two, three or at least one dose of HPV vaccine. Main outcome measures Cervical abnormalities, as predicted by low-grade or high-grade cytology, by number of vaccine doses, stratified by age. Results The sample consisted of 7785 women (mean age 27.5 years, SD 2.3). Overall, 391 (5.0%) were vaccinated with ≥1 dose and 893 (11.5%) had abnormal cytology. Women receiving at least one vaccine dose were significantly less likely to have an abnormal cytology (adjusted odds ratio 0.52; 95% confidence interval 0.34-0.79). Similar results were observed for women receiving a single dose, for both bivalent and quadrivalent vaccines, and applying buffer periods (excluding cytological outcomes within 1 month, 6 months and 1 year of the first dose). Conclusions In the context of an organised cervical screening programme in Italy, catch-up HPV vaccination almost halved the risk of cytological abnormalities. Tweetable abstract Among Ferrara women, vaccination against human papillomavirus halved the risk of screening cervical abnormalities.

Objective: To investigate the outcome of pregnancies with small baby, including both small for gestational age (SGA) and late fetal growth restriction (FGR) fetuses, undergoing induction of labor (IOL) with Dinoprostone, Misoprostol or mechanical methods. Study design: Medline, Embase and Cochrane databases were searched. Inclusion criteria were non-anomalous singleton pregnancies complicated by the presence of a small fetus, defined as a fetus with estimated fetal weight (EFW) or abdominal circumference (AC) 3rd centile with normal cerebroplacental Dopplers). Quality assessment of each included study was performed using the Risk of Bias in Non-randomized Studies-of Interventions tool (ROBINS-I), while the GRADE methodology was used to assess the quality of the body of retrieved evidence. Meta-analyses of proportions and individual data random-effect logistic regression were used to analyze the data. Results: 12 studies (1711 pregnancies) were included. In the overall population of small fetuses, composite adverse intra-partum outcome occurred in 21.2 % (95 % CI 10.0−34.9) of pregnancies induced with Dinoprostone, 18.0 % (95 % CI 6.9−32.5) of those with Misoprostol and 11.6 % (95 % CI 5.5−19.3) of those undergoing IOL with mechanical methods. Cesarean section (CS) for non-reassuring fetal status (NRFS) was required in 18.1 % (95 % CI 9.9−28.3) of pregnancies induced with Dinoprostone, 9.4 % (95 % CI 1.4−22.0) of those with Misoprostol and 8.1 % (95 % CI 5.0−11.6) of those undergoing mechanical induction. Likewise, uterine tachysystole, was recorded on CTG in 13.8 % (95 % CI 6.9−22.3) of cases induced with Dinoprostone, 7.5 % (95 % CI 2.1−15.4) of those with Misoprostol and 3.8 % (95 % CI 0–4.4) of those induced with mechanical methods. Composite adverse perinatal outcome following delivery complicated 2.9 % (95 % CI 0.5−6.7) newborns after IOL with Dinoprostone, 0.6 % (95 % CI 0–2.5) with Misoprostol and 0.7 % (95 % CI 0–7.1) with mechanical methods. In pregnancies complicated by late FGR, adverse intrapartum outcome occurred in 25.3 % (95 % CI 18.8−32.5) of women undergoing IOL with Dinoprostone, compared to 7.4 % (95 % CI 3.9−11.7) of those with mechanical methods, while CS for NRFS was performed in 23.8 % (95 % CI 17.3−30.9) and 6.2 % (95 % CI 2.8−10.5) of the cases, respectively. Finally, in SGA fetuses, composite adverse intrapartum outcome complicated 8.4 % (95 % CI 4.6−13.0) of pregnancies induced with Dinoprostone, 18.6 % (95 % CI 13.1−25.2) of those with Misoprostol and 8.7 (95 % CI 2.5−17.5) of those undergoing mechanical IOL, while CS for NRF was performed in 8.4 % (95 % CI 4.6−13.0) of women induced with Dinoprostone, 18.6 % (95 % CI 13.1−25.2) of those with Misoprostol and 8.7 % (95 % CI 2.5−17.5) of those undergoing mechanical induction. Overall, the quality of the included studies was low and was downgraded due to considerable clinical and statistical heterogeneity. Conclusions: There is limited evidence on the optimal type of IOL in pregnancies with small fetuses. Mechanical methods seem to be associated with a lower occurrence of adverse intrapartum outcomes, but a direct comparison between different techniques could not be performed.

The epidermal growth factor receptor (EGFR) interacts with various downstream molecules including phospholipase C (PLC)/protein kinase C (PKC), Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/GSK-3, Jak/STAT and others. Often these pathways are deregulated in human malignancies such as breast cancer. Various therapeutic approaches to inhibit the activity of EGFR family members including small molecule inhibitors and monoclonal antibodies (MoAb) have been developed. A common problem with cancer treatments is the development of drug-resistance. We examined the effects of a conditionally-activated EGFR (v-Erb-B:ER) on the resistance of breast cancer cells to commonly used chemotherapeutic drugs such as doxorubicin, daunorubicin, paclitaxel, cisplatin and 5-flurouracil as well as ionizing radiation (IR). v-Erb-B is similar to the EGFR-variant EGFRvIII, which is expressed in various cancers including breast, brain, prostate. Both v-Erb-B and EGFRvIII encode the EGFR kinase domain but lack key components present in the extracellular domain of EGFR which normally regulate its activity and ligand-dependence. The v-Erb-B oncogene was ligated to the hormone binding domain of the estrogen receptor (ER) which results in regulation of the activity of the v-Erb-ER construct by addition of either estrogen (E2) or 4-hydroxytamoxifen (4HT) to the culture media. Introduction of the v-Erb-B:ER construct into the MCF-7 breast cancer cell line increased the resistance to the cells to various chemotherapeutic drugs, hormonal-based therapeutics and IR. These results point to the important effects that aberrant expression of EGFR kinase domain can have on therapeutic resistance.

To assess the rate of fetal loss following amniocentesis or chorionic villus sampling (CVS) in twin pregnancy.MEDLINE, EMBASE and Cochrane databases were searched for studies reporting procedure-related complications following amniocentesis or CVS in twin pregnancy. The primary outcome was the rate of procedure-related fetal loss. The secondary outcomes were fetal loss occurring before 24 weeks of gestation and fetal loss occurring within 4 weeks after the procedure. Head-to-head meta-analyses were used to compare directly each outcome, between women undergoing amniocentesis and those not undergoing amniocentesis and between women undergoing CVS and those not undergoing CVS, and to compute pooled risk differences (RD) between women exposed and those not exposed to each invasive procedure. Additionally, meta-analyses of proportions were used to estimate the pooled rates of each of the three outcomes in women undergoing amniocentesis or CVS and in controls.Sixteen studies (3419 twin pregnancies undergoing and 2517 not undergoing an invasive procedure) were included. Head-to-head meta-analyses comparing directly twin pregnancies undergoing and those not undergoing amniocentesis showed a higher risk for overall fetal loss in those undergoing amniocentesis (odds ratio (OR), 1.46 (P = 0.04); RD, 0.013 (P = 0.04)), while there was no difference in the risk of either fetal loss before 24 weeks of gestation (OR, 1.59 (P = 0.06); RD, 0.010 (P = 0.11)) or fetal loss within 4 weeks after the procedure (OR, 1.38 (P = 0.3); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.4% (95% CI, 1.4-3.6%) in twin pregnancies undergoing amniocentesis compared with 2.4% (95% CI, 0.9-4.6%) in those not undergoing amniocentesis. Head-to-head meta-analyses directly comparing twin pregnancies undergoing and those not undergoing CVS showed no significant difference in either overall fetal loss (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)) or fetal loss before 24 weeks of gestation (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.0% (95% CI, 0.0-6.5%) in twin pregnancies undergoing CVS compared with 1.8% (95% CI, 0.3-4.2%) in those not undergoing CVS.The risk of fetal loss following amniocentesis and CVS in twins is lower than reported previously and the rate of fetal loss before 24 weeks of gestation, or within 4 weeks after the procedure, did not differ from the background risk in twin pregnancy not undergoing invasive prenatal testing. These data can guide prenatal counseling for twin pregnancies undergoing invasive procedures. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.Riesgo de pérdida del feto tras una amniocentesis o una biopsia de vellosidades coriónicas en un embarazo de gemelos: revisión sistemática y metaanálisis OBJETIVO: Evaluar la tasa de pérdida del feto tras una amniocentesis o una biopsia de vellosidades coriónicas (BVC) en un embarazo de gemelos. MÉTODOS: Se hizo una búsqueda en las bases de datos MEDLINE, EMBASE y Cochrane de estudios que habían reportado complicaciones relacionadas con el procedimiento después de una amniocentesis o una BVC en un embarazo de gemelos. El resultado primario fue la tasa de pérdida del feto relacionada con el procedimiento. Los resultados secundarios fueron la pérdida del feto producida antes de las 24 semanas de gestación y la pérdida del feto producida dentro de las 4 semanas posteriores al procedimiento. Se utilizaron metaanálisis cara a cara para comparar cada resultado directamente, entre las mujeres que se sometieron a una amniocentesis y las que no se sometieron a ella, y entre las mujeres que se sometieron a una BVC y las que no se sometieron a ella, así como para calcular las diferencias de riesgo (DR) combinadas entre las mujeres expuestas y las no expuestas a cada procedimiento agresivo. Además, se utilizaron los metaanálisis de proporciones para estimar las tasas combinadas de cada uno de los tres resultados en las mujeres que se sometieron a amniocentesis o a BVC y en los controles. RESULTADOS: Se incluyeron 16 estudios (3.419 embarazos de gemelos sometidos a un procedimiento agresivo y 2.517 no sometidos). Los metaanálisis cara a cara que compararon directamente los embarazos de gemelos sometidos y no sometidos a amniocentesis mostraron un mayor riesgo de pérdida general del feto en total en los sometidos a amniocentesis (Razón de Momios (RM), 1,46 (P=0,04); DR, 0,013 (P=0,04)), mientras que no hubo diferencias en el riesgo de pérdida del feto antes de las 24 semanas de gestación (RM, 1,59 (P=0,06); DR, 0,010 (P=0,11)) ni en el de las 4 semanas posteriores al procedimiento (RM, 1,38 (P=0,3); DR, 0,003 (P=0,8)). En general, la tasa conjunta de pérdida del feto fue del 2,4% (IC 95%, 1,4-3,6%) en los embarazos de gemelos sometidos a amniocentesis, en comparación con el 2,4% (IC 95%, 0,9-4,6%) en los que no se sometieron a amniocentesis. Los metaanálisis cara a cara que compararon directamente los embarazos de gemelos que se sometieron y que no se sometieron a una BVC no mostraron diferencias significativas ni en la pérdida del feto en total (RM, 1,61 (P=0,5); DR, 0,003 (P=0,8)) ni en la pérdida del feto antes de las 24 semanas de gestación (RM, 1,61 (P=0,5); DR, 0,003 (P=0,8)). En general, la tasa combinada de pérdida del feto fue del 2,0% (IC 95%, 0,0-6,5%) de los embarazos de gemelos sometidos a BVC, comparada con el 1,8% (IC 95%, 0,3-4,2%) de los que no se sometieron a BVC. CONCLUSIÓN: El riesgo de pérdida del feto tras la amniocentesis y la BVC en gemelos es menor que lo reportado en el pasado y la tasa de pérdida del feto antes de las 24 semanas de gestación, o dentro de las 4 semanas posteriores al procedimiento, no difiere de la del riesgo de contexto en los embarazos de gemelos que no se someten a pruebas prenatales agresivas. Estos datos pueden servir de guía para el asesoramiento prenatal de los embarazos de gemelos que se someten a procedimientos agresivos.双胎妊娠中继羊膜穿刺术或绒膜绒毛取样后发生流产的风险:系统评价和荟萃分析 目的: 评估双胎妊娠中继羊膜穿刺术或绒膜绒毛取样(CVS)后发生的流产率。 方法: 在MEDLINE(美国医学文献联机数据库)、EMBASE(荷兰医学文摘数据库)和实证医学资料库中针对报告双胎妊娠中继羊膜穿刺术或CVS后发生与医疗程序相关的并发症进行了搜索。主要结果是与医疗程序相关的流产率。次要结果是发生在孕期24周前的流产和疗程后4周内发生的流产。采用头对头荟萃分析来直接对比每个结果，在已进行过羊膜穿刺术的孕妇与未进行羊膜穿刺术的孕妇之间，并在已经历CVS的孕妇和未经历CVS的孕妇之间进行对比，以计算出暴露于每种侵入性疗程和未暴露于每种侵入性疗程的孕妇之间的汇总风险差异。此外，采用按比例的荟萃分析来评估经历羊膜穿刺术或CVS的孕妇及对照组中三种预后的 每个汇总比率。 结果: 包含了16项研究(经历过侵入性医疗程序的3419个双胎妊娠和未经历侵入性医疗程序的2517个 双胎妊娠)。直接对比经历和未经历羊膜穿刺术的双胎妊娠的头对头荟萃分析，表明经历了羊膜穿刺术的双胎孕妇发生流产的总体风险更高(比值比(OR)，1.46 (P=0.04)；RD, 0.013 (P=0.04))，在孕期24周前(OR, 1.59 (P=0.06); RD, 0.010 (P=0.11))或疗程后四周内(OR, 1.38(P=0.3); RD, 0.003 (P=0.8))，这两种情况的流产风险没有差别。总体来看，经历羊膜穿刺术的双胎妊娠的流产汇总比率为2.4%(95% CI, 1.4-3.6%)，相比之下，未经历羊膜穿刺术的双胎妊娠的流产汇总比率为2.4%(95% CI, 0.9-4.6%)。直接对比经历过和未经历CVS的双胎妊娠的头对头荟萃分析，表明总体流产情况(OR, 1.61 (P=0.5); RD, 0.003 (P=0.8))和孕期24周前的流产情况(OR, 1.61 (P=0.5); RD, 0.003 (P=0.8))无显著差异。总体来看，经历过CVS的双胎妊娠的流产汇总比率为2.0%(95% CI, 0.0-6.5%)，相比之下，未经历CVS的双胎妊娠的流产汇总比率为1.8%(95% CI, 0.3-4.2%)。 结论: 双胎妊娠中继羊膜穿刺术或绒膜绒毛取样(CVS)后发生流产的风险低于以前的报告，而且孕期24周前或疗程后四周内的流产率与未经历侵入性产前检查的双胎妊娠中的背景风险没有差异。这些数据能够为双胎妊娠进行侵入性检查提供产前咨询指导。© 2020 国际妇产科超声学会.

Introduction: To explore the strength of association and the diagnostic accuracy of umbilical (UA), middle cerebral (MCA), uterine arteries pulsatility index (PI) and the cerebroplacental ratio in predicting an adverse outcome when applied to singleton pregnancies at term. Material and methods: Prospective study carried out in a dedicated research ultrasound clinic. Attended clinicians were blinded to Doppler findings. Inclusion criteria were consecutive singleton pregnancies between 36+0 and 37+6weeks of gestation. The primary outcome was a composite score of adverse perinatal outcome. Logistic regression and ROC curve analyses were used to analyze the data. Results: In all, 600 consecutive singleton pregnancies from 36weeks of gestation were included in the study. Mean MCA PI (1.1± 0.2 vs 1.5± 0.4, P&nbsp

AimsThis retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs).Methods and resultsAll adults with SARS-CoV-2 infection in two Italian provinces were followed for a median of 24 days. ARBs and/or ACEi treatments, and hypertension, diabetes, cancer, COPD, renal and major cardiovascular diseases (CVD) were extracted from clinical charts and electronic health records, up to two years before infection. The sample consisted of 1603 subjects (mean age 58.0y; 47.3% males): 454 (28.3%) had severe symptoms, 192 (12.0%) very severe or lethal disease (154 deaths; mean age 79.3 years; 70.8% hypertensive, 42.2% with CVD). The youngest deceased person aged 44 years. Among hypertensive subjects (n = 543), the proportion of those treated with ARBs or ACEi were 88.4%, 78.7% and 80.6% among patients with mild, severe and very severe/lethal disease, respectively. At multivariate analysis, no association was observed between therapy and disease severity (Adjusted OR for very severe/lethal COVID-19: 0.87; 95% CI: 0.50-1.49). Significant predictors of severe disease were older age (with AORs largely increasing after 70 years of age), male gender (AOR: 1.76; 1.40-2.23), diabetes (AOR: 1.52; 1.05-2.18), CVD (AOR: 1.88; 1.32-2.70) and COPD (AOR: 1.88; 1.11-3.20). Only gender, age and diabetes also predicted very severe/lethal disease.ConclusionNo association was found between COVID-19 severity and treatment with ARBs and/or ACEi, supporting the recommendation to continue medication for all patients unless otherwise advised by their physicians.

Objectives: To assess the role of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses presenting with mild or moderate isolated ventriculomegaly (VM) undergoing multiplanar ultrasound evaluation of the fetal brain. Methods: This was a multicenter, retrospective, cohort study involving 15 referral fetal medicine centers in Italy, the UK and Spain. Inclusion criteria were fetuses affected by isolated mild (ventricular atrial diameter, 10.0–11.9 mm) or moderate (ventricular atrial diameter, 12.0–14.9 mm) VM on ultrasound, defined as VM with normal karyotype and no other additional central nervous system (CNS) or extra-CNS anomalies on ultrasound, undergoing detailed assessment of the fetal brain using a multiplanar approach as suggested by the International Society of Ultrasound in Obstetrics and Gynecology guidelines for the fetal neurosonogram, followed by fetal MRI. The primary outcome of the study was to report the incidence of additional CNS anomalies detected exclusively on prenatal MRI and missed on ultrasound, while the secondary aim was to estimate the incidence of additional anomalies detected exclusively after birth and missed on prenatal imaging (ultrasound and MRI). Subgroup analysis according to gestational age at MRI (< 24 vs ≥ 24 weeks), laterality of VM (unilateral vs bilateral) and severity of dilatation (mild vs moderate VM) were also performed. Results: Five hundred and fifty-six fetuses with a prenatal diagnosis of isolated mild or moderate VM on ultrasound were included in the analysis. Additional structural anomalies were detected on prenatal MRI and missed on ultrasound in 5.4% (95% CI, 3.8–7.6%) of cases. When considering the type of anomaly, supratentorial intracranial hemorrhage was detected on MRI in 26.7% of fetuses, while polymicrogyria and lissencephaly were detected in 20.0% and 13.3% of cases, respectively. Hypoplasia of the corpus callosum was detected on MRI in 6.7% of cases, while dysgenesis was detected in 3.3%. Fetuses with an associated anomaly detected only on MRI were more likely to have moderate than mild VM (60.0% vs 17.7%; P < 0.001), while there was no significant difference in the proportion of cases with bilateral VM between the two groups (P = 0.2). Logistic regression analysis showed that lower maternal body mass index (adjusted odds ratio (aOR), 0.85 (95% CI, 0.7–0.99); P = 0.030), the presence of moderate VM (aOR, 5.8 (95% CI, 2.6–13.4); P < 0.001) and gestational age at MRI ≥ 24 weeks (aOR, 4.1 (95% CI, 1.1–15.3); P = 0.038) were associated independently with the probability of detecting an associated anomaly on MRI. Associated anomalies were detected exclusively at birth and missed on prenatal imaging in 3.8% of cases. Conclusions: The incidence of an associated fetal anomaly missed on ultrasound and detected only on fetal MRI in fetuses with isolated mild or moderate VM undergoing neurosonography is lower than that reported previously. The large majority of these anomalies are difficult to detect on ultrasound. The findings from this study support the practice of MRI assessment in every fetus with a prenatal diagnosis of VM, although parents can be reassured of the low risk of an associated anomaly when VM is isolated on neurosonography. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Specific myeloid-related and inositide-specific gene mutations can be linked to myelodysplastic syndromes (MDS) pathogenesis and therapy. Here, 44 higher-risk MDS patients were treated with azacitidine and lenalidomide and mutations analyses were performed at baseline and during the therapy. Results were then correlated to clinical outcome, overall survival (OS), leukemia-free-survival (LFS) and response to therapy. Collectively, 34/44 patients were considered evaluable for response, with an overall response rate of 76.25% (26/34 cases): 17 patients showed a durable response, 9 patients early lost response and 8 patients never responded. The most frequently mutated genes were ASXL1, TET2, RUNX1, and SRSF2. All patients early losing response, as well as cases never responding, acquired the same 3 point mutations during therapy, affecting respectively PIK3CD (D133E), AKT3 (D280G), and PLCG2 (Q548R) genes, that regulate cell proliferation and differentiation. Moreover, Kaplan–Meier analyses revealed that this mutated cluster was significantly associated with a shorter OS, LFS, and duration of response. All in all, a common mutated cluster affecting 3 inositide-specific genes is significantly associated with loss of response to azacitidine and lenalidomide therapy in higher risk MDS. Further studies are warranted to confirm these data and to further analyze the functional role of this 3-gene cluster.

Introduction: The primary aim of this study was to ascertain the strength of association between cerebral blood flow assessed in anterior (ACA), middle (MCA), and posterior (PCA) cerebral arteries and the following clinical outcomes: small for gestational age (SGA), induction of labor (IOL) for oligohydramnios and caesarean section (CS) for nonreassuring fetal status (NRFS) during labor. Material and methods: Retrospective analysis of prospectively collected data on consecutive singleton pregnancies from 40 0/7 to 41 6/7 week of gestation. UA, ACA, MCA, PCA pulsatility index (PI) were measured from 40 weeks of gestations. Furthermore, the ratios between cerebral blood flow and UA (CPR, ACA/UA and PCA/UA) were calculated and correlated with the observed outcomes. Results: Two hundred twenty-four singleton pregnancies were included in the study. Mean PI of either ACA (p = .04), MCA (p = .008), and PCA (p = .003) were lower in the SGA compared to non-SGA group; furthermore, mean PCA PI was significantly lower than MCA PI (p = .04). Furthermore, CPR (p = .016), ACA/UA (p = .02), and PCA/UA (p = .003) were significantly lower in the SGA group compared to controls. UA, ACA, MCA, and PCA PI were higher in women undergoing IOL for oligohydramnios compared to controls. Logistic regression analysis showed that CPR and PCA/UA ratio were independently associated with SGA. SGA, ACA PI, and ACA/UA were independently associated with CS for NRFS. Finally, birthweight centile, were independently associated with IOL oligohydramnios. Despite this, the predictive accuracy of Doppler in detecting any of the explored outcome was only poor to moderate. Conclusion: Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor. However, the predictive accuracy of Doppler at term is only poor to moderate, thus advising against its use in clinical practice as a standalone screening test for adverse perinatal outcome in pregnancies at term. Key Message Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor.

STUDY OBJECTIVE: To clarify the relationship of hypogastric nerves (HNs) with several pelvic anatomic landmarks and to assess any anatomic differences between the 2 sides of the pelvis, both in cadaveric and in vivo dissections. DESIGN: Prospective observational study. SETTING: An anatomic theater for cadaveric dissections and a university hospital for in vivo laparoscopy. PATIENTS: Five nulliparous female cadavers underwent laparotomic dissection; 10 nulliparous patients underwent laparoscopic surgery for rectosigmoid endometriosis without posterolateral parametrial infiltration. INTERVENTIONS: Measurements of the closest distance between HNs and ureters, the midsagittal plane, the midcervical plane, and uterosacral ligaments on both hemipelvises. A comparison of anatomic data of the 2 hemipelvises was conducted. MEASUREMENTS AND MAIN RESULTS: The right and left HNs were identified in all specimens, both on cadavers and in vivo dissections. A wide anatomic variability was reported. Regarding the differences between the 2 hemipelvises, we found that the right HN was significantly (p .05). CONCLUSIONS: Despite a wide anatomic variability of position and appearance, the HNs are reproducibly identifiable using an "interfascial" technique and considering the ureters and uterosacral ligaments as anatomic landmarks.

We thank Ceylan for his interest in our work and the interesting points he raised. We agree that the size of the ascending aorta did not signal coarctation (CoA) because of problems associated with diameter measurements (which are frequently measured on long-axis images) and the small number of cases included. We acknowledge this major weakness of our systematic review.1 Although not statistically significant, a trend toward smaller ascending aorta …

Background : The misuse of antibiotics is one of the leading causes of antibiotic resistance. Paediatric patients are highly involved in this issue, as they are those who receive the largest amount of prescriptions of these drugs. Therefore, this study aimed to investigate the general knowledge regarding the use of antibiotics, as well as the attitudes related to the administration of these drugs to children, amongst parents of children in the paediatric age-group. Methods : In 2014, a multicentre cross-sectional study was conducted amongst parents of children aged 0–14. A questionnaire made up of 33 items was administered in waiting rooms of outpatient departments. Multivariable logistic regression models were performed, in order to assess the potential predictors of a better knowledge about antibiotics. Results : A total of 1247 parents took part to the survey. Around 33% of the samples declared that antibiotics are useful for viral infections, 20.6% that antibiotics are useful for every kind of pain and inflammation, while 14% of the parents stated that they stop giving antibiotics to their children when they start feeling better. Multivariable models showed that males, unemployed and those with lower levels of education are less prone to answer correctly to the questions about antibiotics. Conclusion : The present study demonstrates that parents have a lack of knowledge regarding the use of antibiotics, which results in bad habits and inappropriate attitudes when it comes to giving antibiotics to their children. Attention should be particularly focused on disadvantaged parents.

Background: Prenatal diagnosis of coarctation of the aorta (CoA) is still challenging and affected by high rates of false-positive diagnoses. The aim of this study was to ascertain the strength of association and to quantify the diagnostic accuracy of different ultrasound signs in predicting CoA prenatally. Methods: Medline, Embase, CINAHL, and Cochrane databases were searched. Random-effects and hierarchical summary receiver operating characteristic model meta-analyses were used to analyze the data. Results: Seven hundred ninety-four articles were identified, and 12 (922 fetuses at risk for CoA) articles were included. Mean mitral valve diameter z score was lower ( P z score was higher in fetuses with CoA than in those without CoA ( P =0.01). Mean aortic valve diameter z score was lower in fetuses with CoA than in healthy fetuses ( P ≤0.001), but the ascending aorta diameter, expressed as z score or millimeters, was similar between groups ( P =0.07 and 0.47, respectively). Mean aortic isthmus diameter z scores measured either in sagittal ( P =0.02) or in 3-vessel trachea view ( P z score, the right/left ventricular and pulmonary artery/ascending aorta diameter ratios were higher ( P P =0.02, and P =0.02, respectively) in fetuses with CoA in comparison with controls, although aortic isthmus/arterial duct diameter ratio was lower in fetuses with CoA than in those without CoA ( P P P =0.005), whereas persistent left superior vena cava ( P =0.85), ventricular septal defect ( P =0.12), and bicuspid aortic valve ( P =0.14) did not carry an increased risk for this anomaly. Multiparametric diagnostic models integrating different ultrasound signs for the detection of CoA were associated with an increased detection rate. Conclusions: The detection rate of CoA may improve when a multiple-criteria prediction model is adopted. Further large multicenter studies sharing the same imaging protocols are needed to develop objective models for risk assessment in these fetuses.

This study investigated the fate of the stent inner surface in carotid artery stenting (CAS). In addition, the occurrence of late cerebral micro-embolism after CAS has been studied in order to identify predictors and correlate it with a possible neo-intimal layer. METHODS: A series of patients were evaluated before CAS through aortic arch trans-oesophageal echocardiography. Six months after CAS, the stent coverage by neo-intima and the possible presence of uncovered plaques were determined by high-resolution duplex scanning (5-17-Hz probe and 3D reconstruction). Possible micro-embolic signals (MESs) were evaluated through transcranial duplex scanning (30-min analysis of ipsilateral middle cerebral artery with a 1-4-Hz probe) and correlated with patients' characteristics, intimal media thickness (IMT) (>0.9mm vs. 4mm). Fisher's and Wilcoxon tests were used to evaluate differences across groups for categorical and continuous variables, respectively. RESULTS: In the 68 CASs examined (40 closed cells and 28 open cells), the stent was completely covered by neo-intima in 52 cases (76.4%). Complete coverage was significantly correlated with IMT

Carotid artery stenting (CAS) leads to frequent embolic brain lesions; their source has not been clearly identified yet. In order to investigate this phenomenon, we have evaluated embolic brain lesions (BL) after CAS and correlated them with aortic arch (AA) characteristics.The AAs of 59 patients undergoing CAS under distal protection were evaluated by angiography and transesophageal echocardiography (TEE). AAs were stratified according to morphology (type I and II "simple" vs type III and bovine "difficult"), atherosclerotic arch lesions (complicated: >5 mm or with mobile debris vs uncomplicated: 150). Diffusion weighted imaging (DWI) was performed before and within 24 hours from CAS. New BL were considered ipsilateral (IL) if ipsilateral to the site of CAS and non-ipsilateral (CL) if contralateral to it or bilateral. Normality distribution was by Shapiro-Wilk test (variables reported as medians +/- interquartile range) and statistical significance (P < .05) by Wilcoxon and Fisher's exact test.Difficult arches were present in 17 patients (28.8\%), complicated aortic plaque in 21 (35.5\%), and TI > 150 in 34 (57.6\%). New BL appeared in 34 or 57.6\% patients (6 or 18\% IL and 28 or 82\% CL). The mean number of BL was 5.7 (range, 0 to 20), 4.7 IL, and 5.7 CL, with a median volume of 560.95 +/- 1677.7 mm(3). Type of arch and TI were not correlated with mean number of BL. Mean volume of BL were greater in patients with difficult AA, complicated plaques, and TI > 150 (258 (572) mm(3) vs 15.6 (353) mm(3), P = .2; and 86 (828) mm(3) vs 85.9 (352) mm(3), P = .4 172 (766) mm(3) vs 0 (228) mm(3), P = .06, respectively). In patients with all three AA characteristics, mean number and volume of BL was significantly greater compared with other patients. Specifically, this increase was due mainly to CL (IL 0 (117) mm(3) vs 0 (172) mm(3), P = .9; CL 564 (687) mm(3) vs 0 (133) mm(3), P = .001). None of the technical details considered was correlated with either IL or CL.BL are frequent after protected CAS and are correlated with AA characteristics, thus underlining the role of catheterization maneuvers in determining embolic events. TEE may be useful in patient's selection for CAS

Background. In Italy, the project on the social burden and quality of life (QoL) of patients with haemophilia investigates costs from a society perspective and provides an overview of their quality of life. Moreover, as life expectancy increased in recent years along with new treatment strategies implemented in the last decades, it analyses trends of costs other than drugs simulating impacts during patient whole life. Material and methods. We ran a web-based cross-sectional survey supported by the Italian Federation of Haemophilia Societies in recruiting patients with haemophilia and their caregivers. We developed a questionnaire to collect information on demographic characteristics, healthcare and social services consumption, formal and informal care utilisation, productivity loss and quality of life. In particular, quality of life was assessed through the EuroQoL tool. Last, we applied the illness cost method from a society perspective. Results. On average, quality of life is worse in adult patients compared to child and caregivers: more than 75% of adult patients declare physical problems, 43% of adult patients and 54% of their parents have anxiety problems. Assuming a society perspective, the estimated mean annual total cost per patient in 2012 is 117,732 €. Drugs represent 92% of total costs. Focusing on costs other than drugs, each additional point of EuroQoL tool implies a costs' reduction of 279 €. The impact of age varies across age groups: each added year implies a total decrease of costs up to 46.6 years old. Afterwards, every additional year increases costs. Discussion. Quality of life of patients with haemophilia and their caregivers improved and it influences positively on consumed resources and on their contribution to the social-economic system. Costs other than drugs for patients with haemophilia follow the same trends of general population. © SIMTI Servizi Srl.

Background and aim The aim of this study was to compare the use of insulin glargine and intermediate/long-acting human insulin (HI) in relation to the incidence of complications in diabetic patients. Methods and results A population-based cohort study was conducted using administrative data from four local health authorities in the Abruzzo Region (900,000 inhabitants). Diabetic patients without macrovascular diseases and treated with either intermediate/long-acting HI or glargine were followed for 3-years; the incidence of diabetic (macrovascular, microvascular and metabolic) complications was ascertained by hospital discharge claims and estimated using Cox proportional hazard models. Propensity score (PS) matching was also used to adjust for significant differences in the baseline characteristics between the two groups. Results Overall, 1921 diabetic patients were included: 744 intermediate/long-acting HI and 1177 glargine users. During the 3-year follow-up, 209 (28.1%) incident events of any diabetic complication occurred in the intermediate/long-acting HI and 159 (13.5%) in the glargine group. After adjustment for covariates, glargine users had an HR (95% CI) of 0.57 (0.44–0.74) for any diabetic complication and HRs of 0.61 (0.44–0.84), 0.58 (0.33–1.04) and 0.35 (0.18–0.70) for macrovascular, microvascular and metabolic complications, respectively, compared to intermediate/long-acting HI users. PS analyses supported these findings. Conclusions The use of glargine is associated with a lower risk of macrovascular complications compared with traditional basal insulins. However, limitations inherent to the study design including the short length of observation and the lack of data on metabolic control or diabetes duration, do not allow us to consider this association as a proof of causality.

The treatment of visceral leishmaniasis (VL) is poorly standardized in Italy in spite of the existing evidence. All consecutive patients with VL admitted at 15 Italian centers as inpatients or outpatients between January 2004 and December 2008 were retrospectively considered; outcome data at 1 year after treatment were obtained for all but 1 patient. Demographic characteristics, underlying diseases, diagnostic procedures, treatment regimens and outcomes, as well as side effects were recorded. A confirmed diagnosis of VL was reported for 166 patients: 120 (72.3%) immunocompetent, 21 (12.6%) patients with immune deficiencies other than HIV infection, and 25 (15.1%) coinfected with HIV. Liposomal amphotericin B (L-AmB) was the drug almost universally used for treatment, administered to 153 (92.2%) patients. Thirty-seven different regimens, including L-AmB were used. The mean doses were 29.4 ± 7.9 mg/kg in immunocompetent patients, 32.9 ± 8.6 mg/kg in patients with non-HIV-related immunodeficiencies, and 40.8 ± 6.7 mg/kg in HIV-infected patients ( P < 0.001). The mean numbers of infusion days were 7.8 ± 3.1 in immunocompetent patients, 9.6 ± 3.9 in non-HIV-immunodeficient patients, and 12.0 ± 3.4 in HIV-infected patients ( P < 0.001). Mild and reversible adverse events were observed in 12.2% of cases. Responsive patients were 154 (93.3%). Successes were 98.4% among immunocompetent patients, 90.5% among non-HIV-immunodeficient patients, and 72.0% among HIV-infected patients. Among predictors of primary response to treatment, HIV infection and age held independent associations in the final multivariate models, whereas the doses and duration of L-AmB treatment were not significantly associated. Longer treatments and higher doses of L-AmB were not able to significantly modify treatment outcomes either in the immunocompetent or in the immunocompromised population.

Purpose: This phase II prospective study aimed to evaluate the efficacy and safety of 5-days azacytidine (5d-AZA) in patients with low-risk myelodysplastic syndromes (MDS). Second, single-nucleotide polymorphism (SNP) genetic profile and phosphoinositide-phospholipase C (PI-PLC) β1 levels were studied to evaluate possible biologic markers able to predict the hematologic response. Experimental Design: The study tested a lower intensity schedule of azacytidine. The treatment plan consisted of 75 mg/sqm/d subcutaneous administered for 5 days every 28 days, for a total of 8 cycles. Results: Thirty-two patients were enrolled in the study. The overall response rate was 47% (15 of 32) on intention-to-treat and 58% (15 of 26) for patients completing the treatment program. In this latter group, 5 (19%) achieved complete remission (CR) and 10 (38%) had hematologic improvement, according to the International Working Group (IWG) criteria. Three patients have maintained their hematologic improvement after 37, 34, and 33 months without other treatments. Moreover, 21 and 2 of 26 cases completing 8 cycles were transfusion-dependent for red blood cells and platelets at baseline, respectively. Of these, 7 (33%) and 2 (100%) became transfusion-independent at the end of the treatment program, respectively. Grade 3–4 neutropenia occurred in 28% of patients and 4 patients died early due to infections or hemorrhage. SNP results were not significantly correlated to the clinical outcome, whereas PI-PLCβ1 level anticipated either positive or negative clinical responses. Conclusions: 5d-AZA is safe and effective in a proportion of patients with low-risk MDS. PI-PLCβ1 gene expression is a reliable and dynamic marker of response that can be useful to optimize azacytidine therapy. Clin Cancer Res; 19(12); 3297–308. ©2013 AACR.

OBJECTIVES: The diagnosis and control of hypertension depend on accurate measurement of blood pressure (BP). The literature on the accuracy of BP recording by health professionals is, however, limited, and no study directly interviewed patients in the hospital setting. This multicenter cross-sectional study aimed at evaluating the compliance to current recommendations on BP measurement by health professionals directly from patients and to investigate potential predictors of higher quality in BP recording. METHODS: A trained nurse interviewed a random sample of adult patients hospitalized for an ordinary admission (except in the emergency room) lasting more than one night, without mental disorder, who had their BP routinely measured by the hospital personnel less than 3 h before. The questionnaire contained 15 items on the main procedures that are common to current guidelines. RESULTS: Fourteen public hospitals from seven regions of Italy participated, and 1334 questionnaires were collected. Nine of the recommended practices were followed in the majority (>70%) of BP recordings, whereas some others were infrequent or rare: in 98.6, 82.2 and 81.1% of the participants, respectively, the arm circumference was never recorded, BP was measured only once, and BP was never recorded in both arms. Overall, 10 or more recommended procedures were followed during 33.4% recordings. At multivariate analysis, physicians were less likely than nurses to provide a more accurate BP measurement. CONCLUSIONS: The operator's compliance to some recommendations in BP measurement is unacceptably low. This survey provides detailed indications for medical directors on the procedures and settings to prioritize in educational programs, which are definitely needed.

The occurrence of depression in patients with coronary heart disease (CHD) substantially increases the likelihood of a poorer cardiovascular prognosis. Although antidepressants are generally effective in decreasing depression, their use in patients with CHD is controversial. We carried out a meta-analysis to evaluate the health effects of selective serotonin reuptake inhibitors (SSRIs) versus placebo or no antidepressants in patients with CHD and depression. Observational studies and randomized controlled trials (RCTs) were searched in MEDLINE, EMBASE, PsycINFO, Cochrane Controlled Clinical Trial Register and other trial registries, and references of relevant articles. Primary outcomes were readmission for CHD (including myocardial infarction, unstable angina, and stroke) and all-cause mortality; the secondary outcome was severity of depression symptoms. Seven articles on 6 RCTs involving 2,461 participants were included. One study incorrectly randomized participants, and another was a reanalysis of RCT data. These were considered observational and analyzed separately. When only properly randomized trials were considered (n = 734 patients), patients on SSRIs showed no significant differences in mortality (risk ratio 0.39, 95% confidence interval 0.08 to 2.01) or CHD readmission rates (0.74, 0.44 to 1.23) compared to controls. Conversely, when all studies were included, SSRI use was associated with a significant decrease in CHD readmission (0.63, 0.46 to 0.86) and mortality rates (0.56, 0.35 to 0.88). A significantly greater improvement in depression symptoms was always apparent in patients on SSRIs with all selected indicators. In conclusion, in patients with CHD and depression, SSRI medication decreases depression symptoms and may improve CHD prognosis.

Background Although blood pressure (BP) differences from supine to sitting position have long been recognized, limited data are available on other commonly used body positions. We performed a cross-sectional study to compare BP values obtained in supine, sitting, and Fowler's positions in essential hypertensive subjects. Methods Systolic BP (SBP) and diastolic BP (DBP) were recorded using an automatic oscillometric device. Nine measurements were taken: three measurements, in random order, in supine, Fowler's, and sitting position. Two generalized estimating equations models were used to evaluate potential predictors of SBP and DBP adjusting for heart rate and measurement order. Results The sample consisted of 250 subjects (mean age 66.3 ± 13.4 years; 44.4% males). Measured in supine, Fowler's, and sitting position, mean SBPs were 139.3 ± 14.0; 138.1 ± 13.8; 137.2 ± 13.7 mm Hg, respectively, and mean DBPs 80.1 ± 9.1; 81.9 ± 9.4; 83.0 ± 9.6 mm Hg, respectively. At multivariate analysis, mean SBP significantly decreased if measured in Fowler's and sitting positions, as compared to supine. In contrast, DBP significantly increased. A relevant proportion of subjects showed large differences (≤ or ≥10 mm Hg) in mean SBP across positions: i.e., 30.0% comparing supine vs. sitting SBP. An even higher prevalence of large differences was observed according to the measurement order within the same positions, with no univocal direction (random variation). Conclusions Fowler's position may represent a valid alternative to sitting and supine positions for BP measurement in clinical practice. BP random variability was found to be large regardless of body position, reinforcing the need for operators to closely follow current guidelines that recommend ≥2 recordings at each measurement.

Osteonecrosis (ON) is a rare disabling complication occurring in patients with human immunodeficiency virus (HIV) infection at a higher frequency than in the general population despite effective combination antiretroviral therapy being made available, as recently documented by several retrospective studies. We designed a multicentric case-control study among HIV-infected patients cared for at institutions in the Italian CISAI group (Italian Study Group for Adverse Events in HIV Infection) to search for additional predictors of ON in this special population. All centers which observed at least one case of ON were requested to report data for central re-evaluation. Parallel HIV-positive, ON-free controls were randomly selected and matched with confirmed cases of ON for sex, age and CD4 T-cell counts at the time of HIV diagnosis. Fifteen cases and controls were included in the final sample. Univariate statistical analyses revealed a significant association between ON and exposure to steroids (P = 0.001), exposure to one or more drugs in addition to HAART (Highly Active Anti-Retroviral Therapy) (P = 0.03), high titers of total serum IgE (P = 0.02), loss of working ability (P = 0.03), triglycerides levels over 200 mg/dL before antiretrovirals (P = 0.03) and cholesterol levels over 200 mg/dL before and after antiretrovirals (P = 0.03 and 0.05, respectively). High serum IgE levels and loss of working ability in advance of ON appeared for the first time as possible predictors of ON in HIV patients, while long-term exposure to steroids, combined hyperlipemia and chronic treatment with other drugs in addition to antiretrovirals were confirmed. Predicting and preventing ON in the individual HIV-infected patient is therefore a clinically challenging opportunity. © 2010 The Japanese Society for Bone and Mineral Research and Springer.

Purpose To evaluate the association between the presence of phosphoinositide-phospholipase C β1 (PI-PLCβ1) mono-allelic deletion with the clinical outcome of myelodysplastic syndromes (MDS) patients. Methods PI-PLCβ1, PI-PLCβ4, and PI-PLCγ1 cytogenetic investigations were performed on 80 newly diagnosed MDS patients (18 low risk, 26 intermediate 1, 18 intermediate 2, 18 high risk) comparing the results with the clinical outcome of the patients. Moreover, fluorescent in situ hybridization results were validated by real-time polymerase chain reaction (PCR). Finally, PI-PLCβ1 gene and protein expression were assessed by both real-time PCR and immunocytochemical experiments. Results Collectively, 35 (43.75%) of 80 of the MDS patients showed a specific mono-allelic deletion of PI-PLCβ1. Kaplan-Meier analysis revealed a significant association (P < .0001) between the PI-PLCβ1 mono-allelic deletion and a higher risk of evolution into acute myeloid leukemia (AML), since 23 of 35 MDS patients (65.7%) bearing the PI-PLCβ1 mono-allelic deletion evolved into AML. Even in multivariate analysis, the PI-PLCβ1 mono-allelic deletion retained a higher significance, with a P < .001, as a prognostic factor of evolution into AML (odds ratio [OR] 1.83; 95% CI, 2.26 to 17.24; P = .00045). Finally, PI-PLCβ1 deletion was related to an altered gene and protein expression. Conclusion PI-PLCβ1 mono-allelic deletion is associated with a worse clinical outcome in MDS patients, hinting at the identification of a new group at higher risk of AML evolution and representing a reliable prognostic tool. Moreover, targeting PI-PLCβ1 pathways might emerge as a new therapeutic strategy for MDS.

Phosphoinositide-specific phospholipase C (PI-PLC) beta 1 is a key enzyme in nuclear signal transduction, and it is involved in many cellular processes, such as proliferation and differentiation. In particular, the involvement of the PI-PLC beta 1 gene in erythroid differentiation lead us to investigate this gene in patients affected by high-risk myelodysplastic syndrome (MDS). By using fluorescence in situ hybridization (FISH) analysis, we have previously evidenced that, in MDS patients with normal GTG banding and a fatal outcome, the PI-PLC beta 1 gene undergoes monoallelic and interstitial deletion. Real-time PCR is characterized by high sensitivity, excellent precision and large dynamic range, and has become the method of choice for quantitative gene expression measurements. In the present study, we have performed a relative quantification real-time polymerase chain reaction (PCR) analysis on all of the MDS patients tested for FISH analysis. Furthermore, we have evaluated the expression of the PI-PLC beta 1 gene on healthy donors and the HL60 cell line, which is useful for testing the accuracy of the technology because of its low expression of PI-PLCf beta 1. To analyze and quantify the levels of the two different splicing variants of PI-PLC beta 1 gene (1a and 1b), we have used a TaqMan isoform specific probe. We have seen that all of the MDS patients have higher levels of the PlPLC beta 1 mRNA compared to the HL60 cell line as expected, but lower levels compared to the healthy donors. Furthermore, MDS blasts always express higher levels of PI-PLC beta 1b mRNA compared to PI-PLC beta 1a mRNA. Our data support the contention that the deletion of the PI-PLC beta 1 gene is indeed responsible for a reduced expression of the enzyme. In addition, the splicing isoform 1b, which is only nuclear, seems to be somehow partially preserved compared to the la isoform, which is nuclear and cytoplasmatic, hinting at a possible imbalance of the nuclear versus cytoplasmatic PI-PLC signaling which, in turn, could affect the cell cycle progression of MDS blasts.

The aim of this study was to describe the prevalence and distribution, by gender, of occlusal traits in a sample of Italian students aged 11-14 years (mean 13 +/- 1 years). Using standardized and validated recording criteria, a single operator measured the overjet, overbite, open bite, anterior and posterior crossbites, crowding, coincidence of the upper and lower midlines, and diastema, in 810 secondary school students (53.6 per cent males). Chi-square, t-test statistics, and odds ratios (ORs) with 95 per cent confidence intervals (CI) were used to investigate the relationship between gender and malocclusion characteristic. Logistic regression was used to further analyse the independent association between gender and each outcome measure. Ninety-three per cent of the subjects showed at least one occlusal trait, with one or two anomalies recorded in 63 per cent of children. The prevalence of occlusal traits ranged from 1.1 (negative overjet) to 54 per cent (upper and lower midlines not coincident). Males were more likely than females to show both an increased overbite and an increased overjet, although the latter result was not confirmed by logistic regression (P = 0.05). Multivariate analysis showed a negative association between overbite and misalignment of the lower incisors and lack of coincidence of the upper and lower midlines, whereas subjects with an increased overbite were more likely to have an increased overjet (all P < 0.01). Further studies are required in order to further clarify these findings and to provide accurate estimates of the orthodontic treatment need in Italian adolescents.

The purpose of this study was to evaluate the activity of digastric, sternocleidomastoid, upper trapezius, lower trapezius and cervical muscles in response to maximum voluntary clenching (MVC) of the teeth. Twenty healthy subjects aged 24-31 years were divided into two groups of 10: a resting group and a clenching group. The resting group simply maintained the mandible at rest with teeth apart for two 1-min periods, whereas the clenching group underwent an initial resting period followed after 1-min by a clenching period during which they were required to perform MVC. The electromyography (EMG) responses of each muscle were recorded during all periods, and means and standard deviations of the root mean square EMG were calculated. Within-group and between-group comparisons of EMG activity were made using, respectively, the Sign two-tailed test for two related samples and the Kolmogorov-Smirnov two-tailed test for two independent samples (significance level 0.05). Data indicated a significant increase of EMG activity of the anterior neck muscles (digastric and sternocleidomastoid) during MVC as compared with EMG recorded during resting periods. If confirmed by further research, our findings suggesting an involvement of anterior neck muscles during isometric contraction of the jaw elevator muscles may have clinical implications.