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ObjectiveNon-coeliac gluten sensitivity (NCGS) is characterised by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing foods, in the absence of coeliac disease (CD) and wheat allergy. No biomarkers are available to diagnose NCGS and the gold standard double-blind placebo-controlled gluten challenge is clinically impractical. The aim of our work was to investigate the role of serum zonulin as a diagnostic biomarker of NCGS and to develop a diagnostic algorithm.DesignIn a multicentre study, we enrolled 86 patients with either self-reported or double-blind confirmed NCGS, 59 patients with diarrhoea-predominant IBS (IBS-D), 15 patients with CD and 25 asymptomatic controls (AC). Zonulin serum levels were assessed and the associated diagnostic power calculated. Clinical and symptomatic data were recorded. The effect of diet on zonulin levels was evaluated in a subgroup of patients with NCGS.ResultsCompared with ACs, the NCGS, irrespective of modality of diagnosis, and patients with CD had significantly increased levels of zonulin, as did both NCGS and patients with CD compared with participants with IBS-D. Self-reported NCGS showed increased zonulin levels compared with double-blind confirmed and not-confirmed NCGS. Six-month wheat avoidance significantly reduced zonulin levels only in HLA-DQ2/8-positive participants with NCGS. The diagnostic accuracy of zonulin levels in distinguishing NCGS from IBS-D was 81%. After exclusion of CD, a diagnostic algorithm combining zonulin levels, symptoms and gender improved the accuracy to 89%.ConclusionZonulin can be considered a diagnostic biomarker in NCGS and combined with demographic and clinical data differentiates NCGS from IBS-D with high accuracy. Wheat withdrawal was associated with a reduction in zonulin levels only in NCGS carrying HLA genotype.

Hyperandrogenic disorders have been associated with psychological distress, reduced quality of life, anxiety and depression. The hypothalamic–pituitary–adrenal (HPA) axis plays a pivotal role in the adaptive response to stressor events. Salivary cortisol (SalF) and cortisone (SalE) testing have been proven to be useful in the evaluation of HPA-axis activity. This study investigated whether SalF and SalE responses to two putative stressor levels differed between the hyperandrogenic states in late adolescent and young women, thus measuring the HPA-axis adaptive response to acute stress events. We selected 161 drug-free females aged 16–19 years from a large population previously enrolled in a cross-sectional epidemiological study. Saliva was collected in the morning before and after two putative stressor events consisting in a self-filled questionnaire (weaker stressor) and in a structured interview plus physical examination by an endocrinologist (stronger stressor). SalF and SalE, as well as blood steroids, were assessed by liquid chromatography–tandem mass spectrometry. Subjects were subdivided into different groups according to the presence of: isolated menstrual irregularities (MI, oligo-amenorrhea; n = 22), isolated hirsutism (HIR, modified Ferriman–Gallwey score ≥ 8; n = 26), isolated hyperandrogenaemia (HT, testosterone >0.438 ng/mL; n = 14), and polycystic ovary syndrome (PCOS, MI with HIR and/or HT, n = 16). The remaining 83 apparently healthy subjects were used as controls. SalF and SalE significantly decreased after the weaker stressor, following the physiologic diurnal loss, in all the groups except for isolated HIR, where they remained unchanged (P = 0.091 and P = 0.118, respectively). In contrast, SalF and SalE remained unchanged after the stronger stressor in isolated MI, isolated HT and controls, whereas SalF increased significantly in isolated HIR (P = 0.011), and SalE increased significantly both in isolated HIR (P = 0.005) and in PCOS (P = 0.011) groups. SalF percentage variation in response to the stronger stressor was positively associated with systolic blood pressure in PCOS (P = 0.018), and both SalF and SalE percentage variations were positively associated with diastolic blood pressure in the isolated HIR group (P = 0.010 and P = 0.006, respectively). In addition, in the isolated HIR group, the SalF percentage variation was negatively associated with HDL cholesterol levels (P = 0.005). Finally, SalF and SalE percentage variations were positively associated with circulating androstenedione (P = 0.031 and P = 0.011, respectively) and DHEA (P = 0.020 and P = 0.003, respectively) in the isolated HIR group. In conclusion, this study demonstrates that hirsute and PCOS adolescent and young women are characterized by HPA-axis overactivity in response to stressful stimuli, as detectable by salivary glucocorticoid measurements. These data also indicate that the higher the HPA-axis activity, the higher the adrenal androgen output and the worse the metabolic profile.

Background and Aims: Excess body weight (EBW) is the most prevalent nutritional disorder among adolescents worldwide. Identifying determinants of EBW may help find new intervention strategies. Behavioral, socio-economic, educational and demographic correlates of EBW were examined in a population of Italian adolescents, separately for males and females. Methods and results: As many as 1039 male and 2052 female students (aged 16–19 ys) attending the last three years of different types of high-school of the Emilia-Romagna region in Italy were offered participation, with 552 males and 841 females being finally evaluated. The prevalence of EBW was 21.0% in males and 14.1% in females. Step-wise multivariate logistic regression analyses were performed showing that EBW was negatively related to energy intake in males (odds ratio for 100 kcal/day (OR) = 0.94, 95% confidence interval (CI): 0.89 to 0.98; P = 0.008), and to father's educational attainment (OR = 0.70, 95% CI: 0.52 to 0.95; P = 0.020), but positively related to parental obesity (OR = 2.80, 95% CI: 1.65 to 4.76; P < 0.001). In females, EBW was positively related to parental obesity (OR = 1.94, 95% CI: 1.15 to 3.29; P = 0.013), but negatively to mother's educational attainment (OR = 0.66, 95% CI: 0.45 to 0.97; P = 0.034) and type of attended school (OR = 0.66, 95% CI: 0.49 to 0.89; P = 0.007). Mother's occupation was also an independent determinant of EBW status in females (OR = 0.39, 95% CI: 0.18 to 0.85; P = 0.018 for being unemployed vs blue-collar). Conclusion: Parental obesity is associated with EBW in male and female adolescents. Importantly, we found sex differences in socio-economic and educational factors impacting on EBW, supporting possible distinct area of investigation.

Background Pathogenesis of acute diverticulitis and diverticular bleeding remains poorly defined, and few data compare directly risk factors for these complications. Aims to assess differences in clinical features, lifestyles factors and concurrent drug use in patients with acute diverticulitis and those with diverticular bleeding. Methods Data were obtained from the REMAD Registry, an ongoing 5-year prospective, observational, multicenter, cohort study conducted on 1,217 patients. Patient- and clinical- related factors were compared among patients with uncomplicated diverticular disease, patients with previous acute diverticulitis, and patients with previous diverticular bleeding. Results Age was significantly lower (OR 0.48, 95% CI: 0.34–0.67) and family history of diverticular disease was significantly higher (OR 1.60, 95% CI: 1.11–2.31) in patients with previous diverticulitis than in patients with uncomplicated diverticular disease, respectively. Chronic obstructive pulmonary disease was significantly higher in patients with previous diverticular bleeding as compared with both uncomplicated diverticular disease (OR 8.37, 95% CI: 2.60–27.0) and diverticulitis (OR 4.23, 95% CI: 1.11–16.1). Conclusion This ancillary study from a nationwide Registry showed that some distinctive features identify patients with acute diverticulitis and diverticular bleeding. These information might improve the assessment of risk factors for diverticular complications.

BackgroundThe morphological characteristics of the largest lymphatic vessels and lymph nodes of the body have been described through ultrasonography, although food and gas in the gastrointestinal tract can often have negative effects on the response of small abdominal structures. The aim of the study was to describe the size of normal abdominal lymph nodes (ALs) in dogs affected by disease, not including lymphadenomegaly or lymphadenopathy, and divided according to body weight and age. The ALs studied included the jejunal, medial iliac, portal, gastric, splenic, and pancreaticoduodenal lymph nodes.ResultsMultiple statistical analyses among the three groups showed that all measurements of the ALs increased according to body weight changes (P 0.1). Mixed results emerged from a comparison of weight categories and age; only the jejunal lymph nodes showed a possible correlation (P

PURPOSE: The assessment of liver fibrosis is essential in the management of patients with chronic liver diseases. Liver biopsy is considered the gold standard procedure for this purpose, though the recent development of new elastosonographic techniques to measure liver stiffness (LS) noninvasively is promising. Point quantification elastography (PQE) showed good results but less is known about the level of skill needed to obtain reliable results. The aim of the study was to evaluate the reproducibility of PQE in assessing LS in healthy subjects comparing three operators with different expertise. METHODS: Between December 2012 and April 2013, 50 consecutive healthy volunteers (18 males, 32 females), median age 30 years (range 25–66) and BMI 22.4 (range 16.7–33.6) were submitted to PQE (iU22 Philips, Bothell, WA, USA) by three operators: two US and elastography providers (one expert and one with intermediate skill) and a skilled transient elastography (Fibroscan) operator with no expertise in US. Intra- and inter-observer agreements were assessed by intraclass correlation coefficient (ICC). RESULTS: PQE measurement was obtained in all subjects by all evaluators. No significant differences of mean liver stiffness were found among operators (P = 0.980). Intra-observer agreement was excellent 0.918 (0.941 for expert, 0.917 for intermediate and 0.888 for novice). The ICC of the inter-observer agreement among the three ratters was excellent (0.882) and was higher in normal than overweight patients (0.923 vs. 0.603; P = 0.011). CONCLUSION: PQE is a reliable and reproducible non-invasive method for the assessment of LE, and can be performed also by a non-experienced operator.

The distinction between active inflammation and fibrosis of the bowel wall is essential for therapeutic decisions in stricturing Crohn's disease. We aimed to assess whether real-time elastography (RTE) with strain ratio measurement could be useful in differentiating fibrotic from inflamed bowel strictures and to evaluate the possible relationship between US techniques and the histology of the stenotic bowel wall.Bowel ultrasonography (including RTE, color-Doppler and CEUS examination) was prospectively evaluated in 26 patients with symptomatic stricturing Crohn's disease, before surgery. RTE was adopted to evaluate bowel stiffness: five loops of 20 RTE frames were recorded for each stenotic segment and the mean strain ratio (MSR) was obtained. Histology scoring systems both for inflammation and fibrosis were established for surgical specimens.No significant correlation was found between MSR and fibrosis score (MSR detection was not able to distinguish fibrotic from inflammatory tissue in our selected population. This result could be influenced by the presence of the superimposed inflammation. Larger cohort of patients, further analysis with shear wave elastography, and validated histopathology classification systems for fibrosis and inflammation are necessary to assess if intestinal fibrosis could be reliably detected on the basis of bowel elastic properties.la distinzione tra infiammazione attiva e fibrosi nella parete intestinale è essenziale nel proceso decisionale della terapia nella malattia di Crohn stenosante. Lo scopo del nostro studio era di stabilire se l’elastografia real-time (RTE) con la misurazione dello strain ratio potesse essere utile nel differenziare il tessuto fibrotico da quello infiammatorio nella parete intestinale stenotica, e di valutare la presenza di correlazioni tra le tecniche ecografiche di studio delle anse intestinali e le caratteristiche istologiche dei segmenti analizzati.Lo studio ecografico delle anse intestinali che comprendeva anche RTE, valutazione color-Doppler e CEUS, è stato eseguito in maniera prospettica in 26 pazienti con malattia di Crohn stenosante sintomatica, prima dell’ intervento chirurgico resettivo. La RTE è stata utilizzata per valutare la rigidità della parete intestinale: 5 filmati di 20 frames di elastografia sono stati registrati per ogni segmento stenotico, per ogni frame è stato calcolato lo strain ratio e quindi ne è stata ottenuta la media (MSR). E’ stato poi stabilito uno score istologico per l’ infiammazione e la fibrosi per i pezzi operatori analizzati.non è stata rilevata alcuna correlazione significativa tra MSR e score istologico della fibrosi (P = 0877). Il Color-doppler correlava significativamente con lo spessore di parete e l’ispessimento della sottomucosa (P = 0006 e P = 0032, rispettivamente). Non è stata trovata una correlazione significativa tra il numero di vasi rilevato sul pezzo istologico e gli score color-Doppler e CEUS (P = 0170 e P = 0302, rispettivamente).il calcolo del MSR non si è rivelato un parametro efficace nel distinguere tra tessuto fibrotico ed infiammatorio nella nostra popolazione. Questo risultato è influenzato da vari fattori, tra cui probabilmente la compresenza di infiammazione. Coorti di pazienti più ampie, ulteriori analisi con l’ausilio eventualmente dell’ elastografia shear-wave, e sistemi di classificazione istopatologici validati sia per la fibrosi che per l’infiammazione, risultano necessari per stabilire se la fibrosi intestinale possa essere rilevata in maniera affidabile sulla base delle proprietà elastiche della parete intestinale.

Objective The endocannabinoid system hypertonicity features obesity. Excess circulating 2-arachidonoylglycerol was variously associated with obesity-related metabolic impairment; however, unstandardized experimental and analytical settings have clouded its usefulness as a dysmetabolism biomarker. We aimed at assessing the influence of body mass index (BMI), menopause in women, and aging in men on 2-arachidonoylglycerol relationship with metabolic parameters. Methods Adult, unmedicated women (premenopausal (preMW): n = 103; menopausal (MW): n = 81) and men (n = 144) were stratified in normal weight (NW; BMI: 18.5–24.9 kg/m2), overweight (OW; BMI: 25.0–29.9 kg/m2), and obese (OB; BMI ≥ 30.0 kg/m2) classes. Anthropometric and metabolic parameters were determined. Plasma 2-arachidonoylglycerol was measured by a validated liquid chromatography-mass spectrometry assay. Results 2-arachidonoylglycerol level was raised by menopause (P, Highlights • Plasma 2AG is a biomarker of dysmetabolism rather than obesity. • Menopause is a major determinant of plasma 2AG levels in females. • Increased plasma 2AG level features obese premenopausal females and obese males. • 2AG is a biomarker of dyslipidemia and insulin resistance in lean menopausal women. • 2AG is a biomarker of dyslipidemia and age-related insulin resistance in lean men.

Objective: This study was designed to assess the steroid profiling by liquid chromatography coupled with tandem mass spectrometry in PCOS women with different phenotypes. Design: Cross-sectional study. Setting: University hospital of Bologna, Italy. Patients and Methods: A total of 156 PCOS women and 141 controls comparable for age were investigated. All underwent a steroid profiling by liquid chromatography coupled with tandem mass spectrometry. Metabolic parameters were also investigated and hirsutism was measured by the modified Ferriman-Gallwey (mF-G) score. Results: Three distinct phenotypes were initially defined according to the combination of hirsutism (mF-G ≥ 8) and/or high testosterone (T) (HA), oligo-amenorrhea (OA), and polycystic ovarian morphology (PCOm); OA + PCOm (n = 43), HA + OA (n = 65), and HA + OA + PCOm (n = 45). T, androstenedione (A), and free androgen index (FAI) levels progressively increased in the 3 PCOS phenotypes with respect to the controls, with the highest values in the HA + OA + PCOm phenotype. The various combinations of hirsutism, high T, high A, and high FAI made it possible to categorize the 3 original phenotypes into 8 hyperandrogenic subgroups, characterized by divergent additional steroid profile and metabolic pattern. A total of 90% of patients with PCOS thus proved hyperandrogenic. Interestingly, half the PCOS women originally classified as having the OA-PCOm phenotype were categorized in a hyperandrogenic subgroup. No significant correlation was found between T, A, and the mF-G score. In contrast, significant correlation was found between A and both T and FAI. Conclusions: This study provides evidence that, by including a steroid profile in the definition of hyperandrogenemia, the majority of women with PCOS are hyperandrogenic, although a clinical and biochemical heterogeneity exists. In addition, these data demonstrate that hirsutism and high androgen levels cannot be used indifferently to define hyperandrogenism.

This paper summarizes the presentations submitted for publication of the 12th AIST National Congress (Associazione Italiana Studio Tosse/Italian Association for Cough Study) entitled “The thousand facets of cough. A clinical and therapeutic update”, which occurred last February 2nd-3rd, 2018 in Bologna (Italy). It summarizes the contributions from leading experts of the sector, who, as in the previous editions, also this year have analyzed a problem too often underestimated which still has many dark sides as regards both the diagnosis and the therapy of cough. The Scientific Committee has chosen topics that had less space in previous editions and these are topical subjects representing a concrete opportunity for learning and comparison of opinions, as well as indispensable elements for the correct management of the symptoms. Hereby we report the abstracts of the works submitted for publication in this Meeting report. The main topics have covered Cough relationship with nerve vagus, ATP, air pollution, GERD, imaging, COPD, pediatric and therapy. Of particular interest it is the preliminary data on cough hydration ratio that shows a highly significant correlation between dehydration and cough. Electronic supplementary material The online version of this article (10.1186/s40248-018-0130-y) contains supplementary material, which is available to authorized users.

Objective N-acylethanolamines play different roles in energy balance; anandamide (AEA) stimulates energy intake and storage, N-palmitoylethanolamide (PEA) counters inflammation, and N-oleoylethanolamide (OEA) mediates anorectic signals and lipid oxidation. Inconsistencies in the association of plasma N-acylethanolamines with human obesity and cardiometabolic risk have emerged among previous studies, possibly caused by heterogeneous cohorts and designs, and by unstandardized N-acylethanolamine measurements. We aimed to characterize changes in the plasma profile, including N-acylethanolamine levels and ratios associated with obesity, menopause in women, and ageing in men, and to define the significance of such a profile as a biomarker for metabolic imbalance. Methods Adult, drug-free women (n = 103 premenopausal and n = 81 menopausal) and men (n = 144) were stratified according to the body mass index (BMI) into normal weight (NW; BMI: 18.5–24.9 kg/m2), overweight (OW; BMI: 25.0–29.9 kg/m2), and obese (OB; BMI ≥30.0 kg/m2). Anthropometric and metabolic parameters were determined. Validated blood processing and analytical procedures for N-acylethanolamine measurements were used. We investigated the effect of BMI and menopause in women, and BMI and age in men, as well as the BMI-independent influence of metabolic parameters on the N-acylethanolamine profile. Results BMI and waist circumference directly associated with AEA in women and men, and with PEA in premenopausal women and in men, while BMI directly associated with OEA in premenopausal women and in men. BMI, in both genders, and waist circumference, in women only, inversely associated with PEA/AEA and OEA/AEA. Menopause increased N-acylethanolamine levels, whereas ageing resulted in increasing OEA relative abundance in men. AEA and OEA abundances in premenopausal, and PEA and OEA abundances in lean menopausal women, were directly associated with hypertension. Conversely, PEA and OEA abundances lowered with hypertension in elderly men. Insulin resistance was associated with changes in N-acylethanolamine ratios specific for premenopausal (reduced PEA/AEA and OEA/AEA), menopausal (reduced OEA/AEA) women and men (reduced OEA/AEA and OEA/PEA). PEA and OEA levels increased with total cholesterol, and OEA abundance specifically increased with HDL-cholesterol. Elevated triglyceride levels were associated with increased N-acylethanolamine levels only in menopausal women. Conclusions Obesity-related N-acylethanolamine hypertone is characterized by imbalanced N-acylethanolamine ratios. The profile given by a combination of N-acylethanolamine absolute levels and ratios enables imbalances to be identified in relationship with different metabolic parameters, with specific relevance according to gender, menopause and age, representing a useful means for monitoring metabolic health. Finally, N-acylethanolamine system appears a promising target for intervention strategies., Highlights • Obesity is featured by plasma N-acylethanolamine excess and imbalanced ratios. • AEA excess is a biomarker of abdominal fat irrespectively of sex and menopause/age. • PEA and OEA protect from hypertension in gender and menopause/age specific fashion. • AEA excess in women and OEA deficiency in men are biomarkers of insulin resistance. • High AEA in men and low OEA in men and menopausal women reflect low HDL-cholesterol.

Objective: The revascularization of critical limb ischemia (CLI) in hemodialysis (HD) patients features poor results in terms of patient survival and limb salvage. Recent predictive models in CLI revascularization did not specifically address HD patients. The aim of this study was to define risk factors for clinical success (CS) after revascularization of CLI in HD patients and to transform findings in a prognostic score. Methods: A retrospective study was conducted of prospectively gathered data, including consecutive HD patients treated for CLI from January 2004 to December 2012. Patients' demographics, comorbidities, CLI stage (Rutherford classification), tissue loss (Texas University Wound classification [TUWC]), and type of revascularization were assessed. End points were CS after revascularization (amputation-free and reintervention-free survival) and a prognostic score for CS based on significant risk factors (multivariable analysis). Results: In the study period, 131 patients (mean age, 70.2 ± 9.9 years; male, 76.3%) with a total of 180 limbs were treated. Endovascular (52.8%), surgical (28.9%), or hybrid (10.6%) revascularization was performed in 163 (90.6%) limbs in 117 patients. The mean (± standard deviation) follow-up was 20.8 ± 21.1 months. Considering revascularized patients, CS was 47.9%, 30.8%, and 17.8% at 6, 12, and 24 months, respectively. On multivariable analysis, age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.05; P =.005), coronary artery disease (CAD; HR, 1.55; 95% CI, 1.04-2.32; P =.032), and TUWC stage D (HR, 1.80; 95% CI, 1.22-2.67; P =.003) were independent negative factors. Type of revascularization had no influence on CS. The score for predicting CS was 0.026 × age (years) + 0.441 × CAD + 0.59 × TUWC stage D. CAD and TUWC stage D were 1 in the presence of disease and 0 in the absence of disease. The score has a significant discrimination power of 75.5% (P =.036), with a best cutoff value of 2.07. Patients with a CS score 2.07 would have a high risk. There were 31 (26.5%) cases of low-risk score and 86 (73.5%) cases of high-risk score. Cases with low-risk score had a CS at 1 year of 51.6% compared with 23.3% in cases with high-risk score. Conclusions: CS after revascularization in HD patients remains poor independent of the type of revascularization. A prognostic model based on age, history of CAD, and severity of CLI (TUWC stage D lesion) can estimate an individual's chances of CS and may help in the decision-making process.

OBJECTIVE: To explore the characteristics of diabetes mellitus in adults with Turner syndrome. DESIGN: Observational study consisting of a prospective phase after the access of adults with Turner syndrome to the Endocrinology Unit (median period of follow-up 15.6, interquartile range: 12.0-24.5 months) and a retrospective collection of data from the diagnosis of Turner syndrome until the time of access to the Endocrinology Unit. A total of 113 Italian Turner syndrome patients were included in the study. During the prospective phase of the study, each patient underwent physical examination, fasting blood sampling, and an oral glucose tolerance test on a yearly basis. Oral glucose tolerance test was used to perform the diagnosis of diabetes mellitus. RESULTS: Before access to the Endocrinology Unit, diabetes mellitus was diagnosed in two Turner syndrome patients. Another five cases of diabetes mellitus were diagnosed at the first access to the Endocrinology Unit, whereas seven new cases of diabetes mellitus were diagnosed during the prospective phase of the study. At the diagnosis of diabetes mellitus, only one patient had fasting glucose above 126 mg/dL, and only two had an HbA1c value >6.5% (48 mmol/mol). When compared to normo-glucose tolerant patients, the diabetic patients had a significantly lower insulin-to-glucose ratio at 30 and 60 min of the oral glucose tolerance test. In the regression analyses, only age was associated with the development of diabetes mellitus. CONCLUSIONS: This study confirms that diabetes mellitus is frequent in Turner syndrome and suggests that it is specific to the syndrome. In addition, this study demonstrates that oral glucose tolerance test is a more sensitive test than HbA1c for the diagnosis of diabetes mellitus in Turner syndrome.

Objective To assess whether sonographic diagnosis of fetal head position before instrumental vaginal delivery can reduce the risk of failed vacuum extraction and improve delivery outcome. Methods Randomised Italian Sonography for occiput POSition Trial Ante vacuum (R.I.S.POS.T.A.) is a randomized controlled trial of term (37 + 0 to 41 + 6 weeks' gestation) singleton pregnancies with cephalic presentation requiring instrumental delivery by vacuum extraction, which was conducted between April 2014 and June 2017 and involved 13 Italian maternity hospitals. Patients were randomized to assessment of fetal head position before attempted instrumental delivery by either vaginal examination (VE) alone or VE plus transabdominal sonography (TAS). Primary outcome was incidence of emergency Cesarean section due to failed vacuum extraction. A sample size of 653 women per group was planned to compare the primary outcome between the two groups. The sample size estimation was based on the hypothesis that the risk of failed vacuum delivery in the VE group would be 5% and that ultrasound assessment of fetal position prior to vacuum extraction would decrease this risk to 2%. Results On interim analysis, the trial was stopped for futility. During this period, 222 women were randomized and 221 were included in the final data analysis, of whom 132 (59.7%) were randomized to evaluation of fetal head position by VE only and 89 (40.3%) to assessment by VE plus TAS prior to vacuum extraction. No significant differences were observed between the two groups with respect to incidence of emergency Cesarean section due to failed instrumental delivery and other maternal and fetal outcomes. Women randomized to assessment by VE plus TAS showed higher incidence of non-occiput anterior position of the fetal head at randomization and lower incidence of incorrect diagnosis of occiput position compared with women undergoing assessment by VE alone. A higher rate of episiotomy was noted in the women undergoing both VE and TAS compared with those in the VE-only group. Conclusions Our prematurely discontinued randomized controlled trial did not demonstrate any benefit in terms of reduced risk of failed instrumental delivery or maternal and fetal morbidity in women undergoing sonographic assessment of fetal head position prior to vacuum extraction. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

To assess the inter-operator concordance and the potential sources of discordance in defining response to sorafenib in hepatocellular carcinoma (HCC). All patients who received sorafenib between September 2008 and February 2015 were scrutinised for this retrospective study. Images were evaluated separately by three radiologists with different expertise in liver imaging (operator 1, >10 years; operator 2, 5 years; operator 3, no specific training in liver imaging), according to: response evaluation radiological criteria in solid tumours (RECIST) 1.1, modified RECIST (mRECIST) and response evaluation criteria in cancer of the liver (RECICL). The overall response concordance between the more expert operators was good, irrespective of the criteria (RECIST 1.1, ĸ = 0.840; mRECIST, ĸ = 0.871; RECICL, ĸ = 0.819). Concordance between the less expert operator and the other colleagues was lower. The most evident discordance was in target lesion response assessment, with expert operators disagreeing mostly on lesion selection and less expert operators on lesion measurement. As a clinical correlate, overall survival was more tightly related with “progressive disease” as assessed by the expert compared to the same assessment performed by operator 3. Decision on whether a patient is a responder or progressor under sorafenib may vary among different operators, especially in case of a non-specifically trained radiologist. Regardless of the adopted criteria, patients should be evaluated by experienced radiologists to minimise variability in this critical instance. • Inter-operator variability in the assessment of response to sorafenib is poorly known. • The concordance between operators with expertise in liver imaging was good. • Target lesions selection was the main source of discordance between expert operators. • Concordance with non-specifically trained operator was lower, independently from the response criteria. • The non-specifically trained operator was mainly discordant in measurements of target lesions.

Obstructive sleep apnoea syndrome is the periodic reduction or cessation of airflow during sleep together with daytime sleepiness. Its diagnosis requires polysomnographic evidence of 5 or more episodes of apnoea or hypopnoea/hour of sleep (apnoea/hypopnoea index, AHI). Volumetric 3-dimensional computed tomographic (CT) reconstruction enables the accurate measurement of the volume of the airway. Nasal continuous positive airway pressure (CPAP) is the conventional non-surgical treatment for patients with severe disease. Operations on the soft tissues that are currently available give success rates of only 40%-60%. Maxillomandibular advancement is currently the most effective craniofacial surgical technique for the treatment of obstructive sleep apnoea in adults. However, the appropriate distance for advancement has not been established. Expansion of the air-flow column volume did not result in an additional reduction in AHI, which raises the important issue of how much the maxillomandibular complex should be advanced to obtain an adequate reduction in AHI while avoiding the risks of overexpansion or underexpansion. We have shown that there is a significant linear relation between increased absolute upper airway volume after advancement and improvement in the AHI (p=0.013). However, increases in upper airway volume of 70% or more achieved no further reduction in the AHI, which suggests that the clinical improvement in AHI reaches a plateau, and renders further expansion unnecessary. This gives a new perspective to treatment based on the prediction of changes in volume, so the amount of sagittal advancement can be tailored in each case, which replaces the current standard of 1cm.

The aim of this study was to evaluate the safety of pancreatic resections in patients 80 years or older.A systematic search of the literature was carried out that compared perioperative outcomes after pancreatic resection in patients 80 years or older with patients younger than 80 years. The primary end points were postoperative mortality and morbidity. The secondary end points were incidence of postoperative pancreatic fistula, delayed gastric emptying, bile leak, pneumonia, postoperative infection, cardiologic complications, reoperation, and length of hospital stay.Nine studies were found to be suitable for the meta-analysis. The postoperative mortality and morbidity were significantly higher in the group 80 years or older (P0.00001 and P = 0.003, respectively) except for patients in whom there were no differences in preoperative comorbidities (P = 0.56 and P = 0.36, respectively). Postoperative cardiac complications were significantly more frequent in patients 80 years or older (P0.0001), and the length of hospital stay was significantly longer in octogenarian patients (P = 0.008).Patients 80 years or older have an increased incidence of postoperative mortality, morbidity, and cardiac complications and a longer length of hospital stay than do younger patients. Thus, pancreatic resection can be recommended only in a selected group of patients 80 years or older.

Context: Low testosterone (T) levels are often found in obese men with impaired glucose tolerance (IGT) and overt type 2 diabetes (T2DM); however, the mechanisms underlying this condition and its correct therapy are still under debate. Objective: To evaluate the effectiveness of clomiphene citrate (CC) in increasing endogenous T levels in obese men with low serum T and with IGT or T2DM treated with metformin (MET). Design: Cross-over, randomized, double-blind, placebo-controlled study. Methods: 24 obese men, aged 47.3 ±. 6.3 (range 35–55 years), with low T level (≤3 ng/mL) and naïve diagnosis of IGT or T2DM were included. Subjects were randomized to CC 25 mg/day or placebo (Plac) with MET 2 g/day for 3 months. After a 6-week wash-out period, subjects were moved to the alternative arm for additional 3 months. Clinical evaluation and blood exams performed prior to and at the end of treatment. Results Of 24 randomized, 21 were evaluable, classified as IGT (n = 11) or T2DM (n = 10). Compared to baseline levels, T levels increased significantly after 3 months of CC treatment (3.03±0.80 to 5.99±1.67 ng/mL P

OBJECTIVE. The aim of this study is to determine whether any correlation between CT findings and functional parameters exists to predict subclinical glucocorticoid secretion. MATERIALS AND METHODS. This is a retrospective database study of 55 patients with incidentally discovered adenomas, investigated through CT with an adrenal protocol, assessing diameters and attenuation values on the unenhanced and contrast-enhanced phases. Patients underwent blood cortisol and corticotropin evaluation and overnight dexamethasone suppression test (DST), in accordance with clinical recommendations. Cortisol levels higher than 50 nmol/L after DST identified subclinical cortisol secretion. We identified 28 subjects with lipid-rich nonsecreting adenomas, nine with lipid-rich secreting adenomas, 11 with lipidpoor nonsecreting adenomas, and seven with lipid-poor secreting adenoma. RESULTS. Cortisol levels after DST were significantly and positively related to mass diameters. At univariate analysis, maximum and minimum diameters and attenuation in the delayed phase were significantly related to the presence of secreting or nonsecreting adenoma; at multivariate analysis, only the minimum diameter and the attenuation in the venous phase entered the stepwise logistic regression. Similarly, minimum diameter and attenuation in the venous phase emerged also at the multivariate stepwise regression between radiologic parameters and cortisol levels after DST. The formula of the radiologic score computed by using the coefficients of the multivariate regression was as follows: (0.1914 × minimum diameter) + (0.0308 × enhanced attenuation). The diagnostic accuracy of this discriminatory score in differentiating secreting from nonsecreting adenomas was 84.9%, the sensitivity was 81.3%, and the specificity was 87.2%. Adenomas with scores greater than 7.59 were considered as secreting adenomas, and adenomas with scores less than 7.36 were considered as nonsecreting adenomas. CONCLUSION. This study shows that imaging parameters can predict subclinical cortisol hypersecretion in patients with adrenal adenomas.

Alessandro Zanasi,1 Luigi Morcaldi,2 Salvatore Cazzato,3 Massimiliano Mazzolini,4 Marzia Lecchi,5 Antonio Maria Morselli-Labate,6 Marianna Mastroroberto,6 Roberto W Dal Negro7 1Italian Association for Cough Study, Bologna, 2National Observatory of Health in Childhood and Adolescence (PAIDOSS: Osservatorio Nazionale sulla Salute dell’Infanzia e dell’Adolescenza), Rome, 3Department of Pediatrics, Salesi Children’s Hospital, Ancona, 4Department of Specialist, Diagnostic and Experimental Medicine, Respiratory and Critical Care Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, 5Department of Biotechnology and Biosciences, University of Milan Bicocca, Milan, 6Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, 7National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy Context: Children’s cough is a daily concern for most pediatricians. The management of both acute and chronic cough requires a systematic and comprehensive approach. Despite the approved protocols for management, the pediatric assessment of cough and the corresponding prescribing attitude frequently do not fit these protocols, which can be affected by parental suggestions – sometimes substantially. Objective: The objective of this study was to investigate both the perception and the behavior of a representative sample of Italian pediatricians toward cough in real life. Methods: A specific questionnaire consisting of 18 questions was prepared. The questionnaire was completed by 300 pediatricians (all members of PAIDOSS: Italian National Observatory on Health of Childhood and Adolescence) who represented ~300,000 children. Results: A vast majority of children have cough throughout the year (99.3% of respondents have cough during autumn/winter and 64.7% in spring/summer). Allergic disease is the most frequent suspected cause of chronic cough in children (53%), and this is supported by the high demand for consultations: 73% seek the opinion of allergologists, 62% of otorhinolaryngologists and only 33% of pulmonologists. The majority of pediatricians (92%) reported that they prescribe therapy in acute cough regardless of cough guidelines. Moreover, the survey pointed out the abuse of aerosol therapy (26% in acute cough and 38% in chronic cough) and of antibiotics prescription (22% in acute cough and 42% in chronic cough). Conclusion: Our survey suggests that some Italian pediatricians’ therapeutic attitudes should be substantially improved in order to achieve better management of cough in children and to minimize the burden of cough. Keywords: acute cough, chronic cough, cough in children, pediatricians’ prescriptions, cough impact

Background Human Cytomegalovirus (HCMV) is the most common cause of childhood hearing loss and can lead to neurodevelopmental delay. To date, few studies have examined the correlation between maternal viremia and congenital HCMV infection. The aim of our study was to ascertain if HCMV DNA in the peripheral blood of pregnant women with primary HCMV infection at the time of amniocentesis may have a prognostic value in terms of congenital infection and neonatal symptomatic disease. Methods We performed a prospective observational study of pregnant women referred to our maternal-fetal medicine division with suspected HCMV infection. Primary infection was diagnosed based on seroconversion for HCMV and/or HCMV immunoglobulin M-positive and low or moderate HCMV immunoglobulin G avidity. At the time of amniocentesis, maternal blood samples were collected and analyzed by means of real-time polymerase chain reaction to determine the presence of viral DNAemia. Fetuses and newborns were evaluated for the presence of congenital infection and symptomatic disease. Results A total of 239 pregnant women were enrolled; 32 blood samples (13.4%) were positive, and 207 (86.6%) were negative for HCMV DNA. The overall rate of transmission was 23.4%. Fifteen infected patients (26.8%) were symptomatic. Vertical transmission occurred in 14 women (43.8%) with positive and 42 (20.3%) with negative results for HCMV DNAemia (P = .006; odds ratio, 3.06; 95% confidence interval, 1.41-6.64). Symptomatic infection occurred in 6 (42.9%) infected fetuses or newborns from women with and in 9 (21.4%) from women without viral DNAemia (P = .16). Conclusion Maternal viremia at amniocentesis is associated with a 3-fold greater chance of congenital infection, but it is not correlated with symptomatic disease.

Purpose To evaluate the quality of life in a 2-year follow-up study in consecutive subjects who underwent pancreaticoduodenectomy with different reconstruction techniques: pancreaticojejunostomy or pancreaticogastrostomy. Patients/methods One hundred and ninety-seven consecutive patients were studied: 164 (83.2%) had malignant and 33 (16.8%) had benign disease. The EORTC QLQ-C30 questionnaire was administered at 5 different time points for evaluation: before surgery, and 6, 12, 18 and 24 months after discharge. Results Pancreaticojejunostomy was performed in 189 patients (95.9%) and pancreaticogastrostomy in 8 patients (4.1%). In the follow-up evaluation, the quality of life significantly improved using the various surgical approaches; improvement over time was not significantly different among the various reconstruction techniques. Conclusions In clinical practice, different surgical reconstruction techniques are equally effective in improving the quality of life after pancreaticoduodenectomy.

Background & Aims Acute infectious gastroenteritis increases the risk for irritable bowel syndrome (IBS) and functional dyspepsia (FD). Children are particularly vulnerable to gastroenteritis because of the immaturity of their intestinal barrier, enteric nervous system, and immune response to pathogens. We investigated whether acute gastroenteritis in early life increases the risk of IBS and FD throughout adulthood. Methods In 1994, we identified and monitored a single culture-proven foodborne Salmonella enteritidis outbreak that involved 1811 patients (mostly pediatric) in Bologna, Italy. Clinical data were collected and a prospective, controlled, cohort study was designed. Long-term effects were assessed by mailing a questionnaire to 757 subjects 16 years after the outbreak (when all of the children were adults). We randomly selected a cohort of 250 adults exposed to Salmonella as children, all 127 individuals exposed as adults, and a cohort of nonexposed participants matched for number, age, sex, and area of residence (controls). Results Among 198 exposed participants, 64 reported FD (32.3%), compared with 51 of 188 controls (27.1%; P = .268). Among 204 exposed participants, 75 reported having IBS (36.8%) compared with 44 of 189 controls (23.3%; P = .004). The odds ratio for IBS among people exposed to the Salmonella was 1.92 (95% confidence interval: 1.23–2.98). The prevalence of IBS was higher in individuals exposed Salmonella as children than in controls (35.3% vs 20.5%; P = .008), but not in individuals exposed as adults, compared with controls. After multivariate logistic regression, post-infectious IBS was independently associated with anxiety and FD. Conclusions Based on data collected from a single culture-proven foodborne Salmonella enteritidis outbreak in 1994, Salmonella -induced gastroenteritis during childhood (but not adulthood) is a risk factor for IBS.

Objectives To assess the intermethod agreement between two-dimensional (2D) and three-dimensional (3D) transperineal ultrasound methods in measuring a new index of fetal head station (the fetal head–symphysis distance (HSD)) in active labor, and to assess potential factors that may affect their agreement. Methods HSD was measured by transperineal ultrasound in 86 women in active labor, once using a 2D and once using a 3D technique. 2D images were acquired first in 43 cases and 3D images were acquired first in the other 43 women. Intermethod agreement between 2D and 3D methods was analyzed by means of intraclass correlation coefficient (ICC) and Bland–Altman analysis. In addition, potential factors affecting the intermethod reproducibility were investigated including fetal occiput position, order of acquisition, fetal head station, stage of labor, maternal body mass index and use of epidural analgesia, using the ANOVA test to check for systematic bias and Levene's test for homoscedasticity. Results Good agreement was demonstrated between 2D and 3D measurements of HSD (ICC, 0.949 (95% CI, 0.914–0.984)). No evidence of systematic difference was shown between the two methods (average difference ± SD = 0.03 ± 2.29 mm; P = 0.888). The only factor that had a significant effect on systematic difference between 2D and 3D methods was order of acquisition (P = 0.042); the first observation was higher regardless of the method used. Fetal head station had a significant effect on the homogeneity between the two methods (P = 0.004) with a better 2D–3D agreement obtained at lower head stations (SD of differences: 1.63 vs 2.59 mm). Conclusions There is very good agreement between 2D and 3D methods of assessing HSD. Agreement is better in lower fetal head stations. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Objective: During the last decades, an increase in the prevalence of asthma and other allergic diseases has been recorded, together with modifications in the living environment and consequent changes in the quality of indoor air. Indoor environment is favorable to the proliferation of allergens such as: house dust mites, fungal spores and cockroaches. The primary action to be undertaken for an effective eradication of infectious agents constitutes in modifying the house environmental conditions, which make it favorable to infestations. Ozone can play a sanitize role, but at the same time it can cause inflammation, especially in the lung. The aim of this study was to verify the role and safety of ozone in the sanitation of the bedroom of a subject suffering from asthma. Methods: A daily ozone treatment was carried during a 14-day time period in the bedroom of an asthmatic patient. Aerobiological sampling in indoor air, microbiological sampling and detection of ATP bioluminescence on the surface were performed before and after treatment at the first day, as well as after treatment at the 7th and 14th day of the study. An aerobiological measurement was also performed outdoor of the patient's bedroom only for the first day. Results: Our analysis confirms that low ozone levels induced a marked reduction of indoor air microbiological pollution without adverse effects on lung functionality of the asthmatic patient we considered. Conclusion: Our observations warrant further investigation on the role that ozone-based sterilization might have in controlling asthmatic symptoms.

OBJECTIVES: Contrast-enhanced ultrasound (CEUS) has been developed to better characterize the microvasculature of solid masses in several organs, including the pancreas. In this study, we assessed CEUS accuracy in differentiating exocrine from endocrine pancreatic tumors. METHODS: A total of 127 patients with single, undetermined pancreatic masses were prospectively examined with transabdominal ultrasound and CEUS, before surgical resection or percutaneous biopsy. RESULTS: Exocrine and endocrine pancreatic tumors showed different intralesional vascularization patterns: 98.9% (90/91) of exocrine tumors were hypoenhancing, whereas 95.8 % (23/24) of endocrine tumors had a hypervascular supply. A hypoenhancing pattern, indicative of ductal adenocarcinoma, had a significant (P < 0.001) diagnostic accuracy of 91.3% with a sensitivity of 96.8%, a specificity of 85.3%, a positive predictive value and a negative predictive value of 94.7% and 90.6%, respectively. The hyperenhancing pattern, indicative of endocrine tumors, had a significant (P = 0.031) diagnostic accuracy of 73.8% with a sensitivity of 83.3%, a specificity of 60.0%, a positive predictive value and negative predictive value of 83.3% and 60.0%, respectively. CONCLUSIONS: Contrast-enhanced ultrasound has a valuable diagnostic accuracy in differentiating exocrine from endocrine pancreatic tumors, which is a fundamental step to address appropriate histological evaluation, therapeutic approach, and follow-up.

PURPOSE: To evaluate, by using a standardized reporting methodology, the perioperative complications and mortality in patients who underwent radical cystectomy. MATERIALS AND METHODS: We retrospectively reviewed all data of 404 consecutive patients who underwent radical cystectomy from 1995 to 2009 for nonmetastatic bladder cancer at the same academic center. Perioperative complications and perioperative mortality were defined as any adverse event or death from any cause within 90 days of surgery. All perioperative complications were reported according to the Martin criteria and were graded according to the Clavien system (grade 1-5). Univariate and multivariate analyses for the clinical and pathologic characteristics were used to evaluate predictors of complications. RESULTS: A total of 296 complications occurred in 209 (51.7%) patients. Among them, 139 (34.4% of the entire population) had only a '"minor"' (grade 1-2) complication, whereas 70 (17.3%) had a "major" (grade 3-5) complication. Eighteen (4.5%) patients died within 90 days after surgery. At univariate analysis, age ≥75 years (2P = .018), serum creatinine level ≥1.4 mg/dL (2P = .025), American Society of Anesthesiologists (ASA) score of 3 to 4 (2P < .001) were significant predictors of complications after 30 days from surgery; conversely, the ASA score was the only significant predictor of complications after 90 days. At multivariate analysis, only the ASA score was independently correlated with the development of complications at 30 and 90 days of follow-up (2P < .001). CONCLUSIONS: Radical cystectomy is one of the most complex procedures in urology, with a high rate of complications and mortality. The use of a standardized methodology is the only way to estimate the actual rate and the severity of complications.

Purpose To investigate the effect of a low-dose oral contraceptive containing drospirenone/ethinylestradiol 3 mg/20 μg on endometrioma mean diameter. Methods Fifty women with sonographic diagnosis of ovarian endometrioma and at least 12 months of therapy with drospirenone/ethinylestradiol 3 mg/20 μg, without previous adnexal surgery, were selected for this retrospective study. Endometrioma mean diameter measured with transvaginal ultrasonography and endometriosis-associated symptoms evaluated by a visual analogue scale (VAS) score (0-10) were reported at therapy prescription (baseline) and after 6, 12 and 18 months of treatment. Main outcome measures were endometrioma mean diameters and endometriosis-associated symptoms variations during the follow-up; differences between cyclic and continuous regimen were also considered. Results A significant reduction in endometrioma mean diameter was observed during the follow-up. The reductions of mean diameter versus baseline values were significantly higher in continuous users than in cyclic users at 6 and 18 months of follow-up. No new endometriomas occurred. The dysmenorrhea VAS score significantly decreased during the follow-up. Conclusions Drospirenone/ethinylestradiol 3 mg/20 μg seems to be effective in reducing endometrioma mean diameter. The continuous regimen seems to be associated with a greater reduction than the cyclic one.

Objective To compare longitudinal changes in angle of progression (AoP) and midline angle (MLA) during the active second stage of labor according to the mode of delivery. Methods A three-dimensional transperineal ultrasound volume was acquired in a series of nulliparous women at the beginning of the active second stage (T1) and every 20 min thereafter (T2, T3, T4, T5 and T6). Following delivery, all ultrasound volumes were analyzed and AoP and MLA were measured. Results Among 71 women included in the study, 58 underwent spontaneous vaginal delivery (Group A) and 13 underwent operative delivery (Group B) (eight by vacuum extraction and five by Cesarean section). When compared with Group B, Group A had a wider AoP only at T1 (140.0 ± 20.2° vs 122.9 ± 16.7°; P = 0.010) and T2 (149.7 ± 20.7° vs 126.9 ± 17.5°; P = 0.006). MLA was narrower in Group A only at T3 (21.2 ± 11.7° vs 40.8 ± 27.9°; P = 0.043), T4 (18.2 ± 15.0° vs 47.4 ± 29.6°; P = 0.020) and T5 (18.3 ± 6.0° vs 34.7 ± 4.2°; P = 0.034). On stepwise forward multiple logistic regression analysis, both AoP and MLA were independently associated with operative delivery (OR = 0.955 and OR = 1.018, respectively). Conclusion Ultrasonographic assessment of fetal head descent in the second stage of labor may play a role in the prediction of the mode of delivery. Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.

Post-viral cough is a type of cough originating from upper respiratory tract infections that persists after the infection is resolved. Although it was hypothesized that bronchodilators might have a role in the management of post-viral cough, a clear demonstration of their efficacy is missing. Therefore, we tested the efficacy of a combination of a β-agonist and an anticholinergic agent in reducing post-viral cough with a randomized, double blind, placebo controlled clinical trial. Patients were treated for 10 days with either a nebulized combination of salbutamol 1.875 mg/0.5 mL and ipratropium bromide 0.375 mg/0.5 mL, or a placebo, and followed up for another 10 days. Daytime and nighttime cough severity and spirometry testing were assessed before starting treatment, after 10 and 20 days. Ninety-two patients were randomized to receive placebo (n = 46) or the active treatment (n = 46); nine of them (4 in the placebo group, 5 in the active treatment group) dropped out from the study. Daytime and nighttime cough severity were significantly reduced in both groups during the study period, but the reduction was more prominent in the active treatment group vs. placebo after 10 days of treatment (P = 0.003 for day cough; P = 0.061 for night cough), whereas at the end of follow-up period cough severity was comparable between the two groups. Small but significant increases in spirometric parameters were observed in the active treatment vs. placebo group, although at the end of follow-up these values returned to be comparable to placebo. The frequency of adverse events was not significantly different between the two groups of patients. We concluded that a combination of a β-agonist and an anticholinergic agent can effectively reduce post-viral cough, and can thus represent a valid option for this type of cough.

Perineural invasion (PNI) hinders the ability to establish local control of oral squamous cell carcinoma (OSCC). To date, PNI can be evaluated only in surgical specimens and not in preoperative biopsy material, rendering timely therapeutic planning impossible. Insulin-like growth factor-II mRNA binding protein-3 (IMP3) expression appears to be of diagnostic and prognostic utility for many solid tumours, and laminin-5 expression in surgical specimens has been identified as a valid predictor of neural spread of head-and-neck neoplasms. The ability to use preoperative biopsy material to identify patients exhibiting PNI is fundamental for good management of OSCC. We examined a series of 64 consecutive patients treated (primarily via surgery) for OSCC between 2009 and 2014 at the Maxillofacial Surgery Unit, University of Bologna. We evaluated IMP3 and laminin-5 expression in preoperative biopsy material using immunohistochemistry and quantitative reverse transcription polymerase chain reaction. We sought to correlate expression of IMP3 and laminin-5 with PNI evident in surgical specimens. Expression of IMP3 and laminin-5 in preoperative biopsy material appeared to be predictive of PNI in patients with OSCC (P

Objectives The purpose of this study was to compare conventional 2-dimensional (2D) B-mode sonography with 3-dimensional (3D) sonography for assessing gallbladder volume and contractility. Methods Gallbladder volume and contractility were evaluated in 32 healthy volunteers after fasting and abstinence from smoking for 8 hours and after a standardized balanced liquid meal. The gallbladder was evaluated with 2D sonography (with the use of the ellipsoid method) and with 3D sonography using a volumetric matrix probe. Both measurements were made by an operator who was skilled in sonography and an unskilled operator. The group of volunteers was subdivided into 2 subgroups including 16 participants, which represented the “2 moments” of acquisition by the techniques, particularly for the unskilled operator. Results The postprandial volumes obtained with 3D sonography were significantly lower in comparison to the volumes obtained with 2D sonography (P= .013), and there was a significant difference between the measurements made by the skilled and unskilled operators only for 2D sonography (P< .001), whereas between the 2 moments of acquisition by the 3D technique, there was no significant difference. The reproducibility of the technique for evaluation of gallbladder volumes was higher for 3D sonography than 2D sonography, particularly for the postprandial evaluation. Conclusions The new 3D sonographic method using a volumetric matrix probe is a simple, reliable, and more reproducible technique than conventional 2D sonography, even if performed by an unskilled operator, and it allows a reliable stimulation test for a gallbladder dynamic study.

Context An increase in enzyme lactate dehydrogenase (LDH) in serum is a negative prognostic factor for survival in cats affected by lymphoma. Measuring LDH at the time of diagnosis has been studied for differentiating neoplastic disease from non-neoplastic disease in dogs. Inflammatory bowel disease (IBD) and alimentary lymphoma are common diseases in cats. Objective The aim of this study was to determine whether elevation of total LDH occurred in cats with alimentary lymphoma and non-neoplastic gastrointestinal disease, such as IBD, and to evaluate whether this enzyme is useful in supporting the differential diagnosis of these specific diseases. Materials and Methods A prospective non-randomized controlled study was carried-out in a real world setting of three Italian private veterinary clinics. Seventy-one client-owned cats with a history of chronic gastrointestinal symptoms were enrolled; 33 cats were histologically diagnosed as having alimentary lymphoma and 38 cats as having IBD. Serum samples of total LDH analysis were measured. Results Gender (P = 0.016) and age (P = 0.046) were found to be significant factors influencing the differentiation of serum total LDH between cats with alimentary lymphoma and those with IBD. Despite low diagnostic accuracy in the overall population (63%), a cut-off value of serum total LDH ranging from 0.85- to 1.04-times the upper reference limit showed good capability (accuracy >80%) of differentiating these two conditions in neutered males and cats younger than 8 years of age (AUC: 0.805, 0.833; sensitivities: 76.9%, 83.3%; specificities: 80.0%, 76.5%; PPV: 76.9%, 55.6%; NPV: 80.0%, 92.9%; respectively). Conclusions Although our study showed that gender and age are significant factors in differentiating serum total LDH between cats with alimentary lymphoma and those with IBD, this test had poor diagnostic accuracy in differentiating between these two conditions in the overall population.

Ovarian tissue cryopreservation (OTC), representing a promising strategy to preserve ovarian function in cancer patients, is recommended to women younger than 35 years. This study aimed to identify endocrine and biometric parameters as additional selection criteria for OTC. One hundred and ninety-one cancer patients before chemoradiotherapy and OTC and 43 controls were investigated. Mean ± SD, median, quartiles, 5th and 95th centiles and correlations of FSH, LH, estradiol, inhibin-B, anti-Mullerian hormone (AMH), ovarian volume and antral follicle count (AFC) were assessed. Most ovarian reserve parameters presented typical variations of ovulatory menstrual cycle, except AMH and AFC showing minimal fluctuations across the menstrual cycle. The 5th centiles of AMH (0.31and 0.4 ng/mL in controls and cancer patients, respectively) and AFC (five follicular structures in both groups) could be conjectured as minimum thresholds to include patients aged

Background Subclinical inflammation and atrial stretch have been recognized as important contributors to atrial fibrillation (AF) onset and perpetuation. The aim of the study was to compare the predictive role of serum inflammatory markers (serum amyloid A [SAA], and C-reactive protein [CRP]) and N-terminal pro brain natriuretic peptide (NT-proBNP) an indice of atrial strain in relation to subacute arrhythmic recurrence rate in patients with persistent AF and normal left ventricular ejection fraction (LVEF). Methods We studied 57 patients with a mean LVEF of 58.7 ± 6%. NT-proBNP, SAA and CRP levels were determined few hours before electrical cardioversion and 3 weeks after cardioversion. Results Subacute AF recurrences were documented in 19 (33 %) patients. Whereas NT-proBNP levels did not predict arrhythmic outcome, higher SAA (> 6.16-6.19 mg/L) and CRP levels (> 2.99-3.10 mg/L) were significantly associated with AF recurrences (odds ratio [OR], 5.39; 95% confidence interval [CI], 1.59-18.26; P = 0.007 and OR, 14.93; 95% CI, 3.90-57.19; P P = 0.009) and high sensitivity CRP (OR, 42.03; 95% CI, 4.83-365.45; P = 0.001) through the multivariate logistic regression analysis show an independent role in predicting the AF recurrence with a sensitivity of 100% (38/38) and a specificity of 52.6% (10/19). Conclusions The present study demonstrates that in patients with persistent AF and preserved LVEF, SAA and CRP levels are independent predictors of AF subacute recurrence rate, whereas NT-proBNP, not associated with arrhythmic outcome, reflects the hemodynamic alterations secondary to arrhythmia presence. The simultaneous determination of SAA and high sensitivity CRP has a very high sensitivity (100%) in predicting the AF recurrence.

The aim of this study was to investigate the diagnostic performance of new dual-energy X-ray absorptiometry (DXA) technologies in the detection of vertebral fractures (VFs). Sixty-eight patients were submitted to DXA and conventional radiography (XR) on the same day. Lateral images of the spine were independently evaluated by three radiologists with different experience in skeletal imaging, in two sessions with 7 days between evaluations of the same anonymous images. The most expert physician repeated the analysis in a subsequent reading session after further 7 days. Results from expert XR evaluation were considered as gold standard. A semiquantitative approach was used to interpret images and morphometric analysis was performed when a VF was suspected. Seventy vertebrae (70/884, 7.9%) were excluded from the lesion-based analysis, as not evaluable: 11/70 (15.7%) missed by XR only, 56/70 (80.0%) missed by DXA only, 3/70 (4.3%) missed by both techniques (upper thoracic spine). Forty “true” fractures were detected (4.9% out of 814 vertebrae) in 26 patients (38.2% of the 68 studied patients). Twenty-five (62.5%) were mild fractures. DXA sensitivity and specificity were 70.0% and 98.3% on a lesion-based analysis, 73.1% and 90.5% on a patient-based analysis. Intra-observer agreement was excellent with no significant difference between the two techniques. Inter-observer agreement among the 3 observers was higher for XR (k = 0.824 versus 0.720 in the detection of VFs, p = 0.011). DXA accuracy was not influenced by radiologist experience; T4-L4 assessability as well as reproducibility and repeatability of the two techniques and accuracy of DXA were independent from sex, age, body mass index, grade of arthrosis. However DXA sensitivity was affected by mild VFs. Vertebral level did not affect the diagnostic performance with exception of vertebral body assessability. Latest improvements make VFs assessment by DXA competitive with traditional radiographic gold standard, providing consistent advantages and attractions. Few limitations still affect DXA performance and need to be overcome.

BackgroundSubclinical Cushing's syndrome (SCS) is defined as alterations in hypothalamic–pituitary–adrenal axis without classic signs/symptoms of glucocorticoid excess. Whether SCS leads to metabolic and cardiovascular diseases is still controversial.AimTo evaluate the prevalence of hypertension, type 2 diabetes (T2D), coronary heart disease (CHD), ischemic stroke, osteoporosis, and fractures, and their relationship to increasing patterns of subclinical hypercortisolism, in patients with nonsecreting adrenal adenomas (NSA) and SCS.MethodsUsing the 1 mg dexamethasone suppression test (DST), 348 patients were classified as follows: 203 were defined as NSA and 19 SCS, using the most stringent cutoff values (138 nmol/l respectively). Patients with cortisol post-DST (50–138 nmol/l) were considered as intermediate phenotypes and classified as minor (n=71) and major (n=55) using plasma ACTH and/or urinary free cortisol as additional diagnostic tools.ResultsSCS patients showed higher prevalence of T2D, CHD, osteoporosis, and fractures with respect to NSA. Intermediate phenotypes also showed higher prevalence of CHD and T2D with respect to NSA. The prevalence of all clinical outcomes was not different between intermediate phenotype patients, which were therefore considered as a single group (IP) for multivariate logistic regression analysis: both IP and SCS-secreting patterns showed a significant association with CHD (odds ratio (OR), 4.09; 95% confidence interval (CI), 1.47–11.38 and OR, 6.10; 95% CI, 1.41–26.49 respectively), independently of other potential risk factors. SCS was also independently associated with osteoporosis (OR, 5.94; 95% CI, 1.79–19.68).ConclusionsPatterns of increasing subclinical hypercortisolism in adrenal adenomas are associated with increased prevalence of adverse metabolic and cardiovascular outcomes, independently of other potential risk factors.

Study question Which is the best method for human ovarian tissue cryopreservation: slow freezing/rapid thawing (SF/RT) or vitrification/warming (V/W)? Summary answer The conventional SF/RT protocol used in this study seems to better preserve the morpho-functional status of human cryopreserved ovarian tissue than the used open carrier V/W protocol. What is known already Cryopreservation of human ovarian tissue is generally performed using the SF/RT method. However, reduction in the follicular pool and stroma damage are often observed. An emerging alternative procedure is represented by V/W which seems to allow the maintenance of the morphological integrity of the stroma. Study design, size, duration This is a retrospective cohort study including six patients affected by oncological diseases and enrolled from January to December 2014. Participants/materials, setting, methods Ovarian tissue was laparoscopically harvested from the right and left ovaries and was cryopreserved using a routinary SF/RT protocol or a V/W method, involving tissue incubation in two solutions (containing propylene glycol, ethylene glycol and sucrose at different concentrations) and vitrification in an open system. For each patient, three pieces from each ovary were collected at the time of laparoscopy (fresh tissue) and after storage (SF/RT or V/W) and processed for light microscopy (LM) and transmission electron microscopy (TEM), to assess the morphological and ultrastructural features of follicles and stroma, and for laser scanning confocal microscopy (LSCM), to determine the functional energetic/redox stroma status. The preservation status of SF/RT and V/W ovarian tissues was compared with that of fresh ones, as well as between them. Main results and the role of chance By LM and TEM, SF/RT and V/W samples showed cryodamage of small entity. Interstitial oedema and increased stromal cell vacuolization and chromatin clumping were observed in SF/RT samples; in contrast, V/W samples showed oocyte nuclei with slightly thickened chromatin and irregular shapes. The functional imaging analysis by LSCM revealed that the mitochondrial activity and intracellular reactive oxygen species levels were reduced both in SF/RT and in V/W samples compared with fresh samples. The study also showed progressive dysfunction of the mitochondrial activity going from the outer to the inner serial section of the ovarian cortex. The reduction of mitochondrial activity of V/W samples compared with fresh samples was significantly higher in the inner section than in the outer section. Limitations, reasons for caution The results report the bioenergetic and oxidative status assessment of fresh and cryopreserved human ovarian tissue by LSCM, a technique recently applied to tissue samples. The use of LSCM on human ovarian tissues after SF/RT or V/W is a new application that requires validation. The procedures for mitochondrial staining with functional probes and fixing are not yet standardized. Xenografting of the cryopreserved ovarian tissue in severe combined immunodeficient mice and in vitro culture have not yet been performed. Wider implications of the findings The identification of a cryopreservation method able to maintain the morpho-functional integrity of the ovarian tissue and a number of follicles comparable with those observed in fresh tissue might optimize results in clinical practice, in terms of recovery, duration of ovarian function and increased delivery outcomes after replanting. The SF/RT protocol allowed better morpho-functional tissue integrity than the V/W procedure. Study funding/competing interests Funding was provided by Fondazione del Monte di Bologna e Ravenna, Italy. Dr N.A.M. was granted by the project ONEV MIUR PONa3 00134-n.254/R&C 18 5 2011 and the project GR-2011-02351396 (Ministry of Health, Young Researchers Grant 2011/2012). There are no competing interests. Trial registration number Clinical trial 74/2001/0 (approved:13 2 2002): 'Pilot study on cryopreservation of human ovarian tissue: morphological and immunohistochemical analysis before and after cryopreservation'.

Background. There is increasing evidence regarding the involvement of inflammation processes in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Aim. To evaluate the circulating concentrations of MMP-3 and TIMP-2 in patients with IPMNs and in those with ductal adenocarcinomas. Patients. Sixty patients (32 males, 28 females, mean age 69.3±11.3 years) were enrolled: 31 (51.7%) had IPMNs and 29 (48.3%) had histologically confirmed pancreatic adenocarcinomas. Thirty blood donors were also studied as controls. Methods. The serum concentrations of MMP-3 and TIMP-2 were determined in all study subjects using commercially available kits. Results. Serum concentrations of MMP-3 were significantly higher both in patients with pancreatic ductal adenocarcinomas and in those with IPMNs as compared to the healthy subjects whereas serum levels of TIMP-2 were significantly lower both in IPMN patients and in patients with pancreatic adenocarcinomas than in those of the healthy subjects. No significant differences in the serum levels of both MMP-3 and TIMP-2 were found between patients with IPMNs and those with pancreatic adenocarcinomas, and, in the patients with IPMN, they were not related to the type of tumor. Conclusions. IPMNs have a pattern of extracellular matrix factors and their inhibitors are similar to those of ductal adenocarcinoma; MMP-3 and TIMP-2 cannot be utilized to routinely differentiate IPMNs from ductal adenocarcinomas.

Background Unlike chronic idiopathic intestinal pseudo-obstruction (CIIP), severe digestive syndromes that are not characterized by episodes resembling mechanical obstruction remain poorly characterized. The present study compared clinical features, small bowel motility, and quality of life (QoL) in patients with CIIP or severe functional gastrointestinal disorders (SFGID), compared to irritable bowel syndrome (IBS). Methods We enrolled 215 consecutive patients: 70 CIIP, 110 malnourished SFGID [body mass index (BMI) 17.8 ± 1.8 kg m−2] and 35 non-malnourished SFGID (BMI 22.8 ± 3.6 kg m−2). Key Results Abnormal motor patterns that fulfilled diagnostic criteria for small bowel dysmotility were virtually absent in IBS patients, but were recorded in69 CIIP patients (98.6%), 82 malnourished SFGID patients (74.5%;), and 23 SFGID patients without malnutrition (65.7%) (P