Lung visualisation on PET/MRI: implementing a protocol with a short echo-time and low flip-angle volumetric interpolated breath-hold examination sequence.

AIM: To assess the diagnostic performance in detecting lung lesions of a short echo-time (TE) and low flip-angle (FA) volumetric interpolated breath-hold examination (VIBE) sequence included in the integrated positron-emission tomography (PET)/magnetic resonance imaging (MRI) protocol. METHOD AND MATERIALS: Thirty-seven oncological patients who underwent computed tomography (CT) and PET/MRI, including both a dedicated short TE, low FA VIBE (modified VIBE) and a standard VIBE of the lung, were enrolled. Modified VIBE images were reviewed retrospectively and independently by three raters, to detect pulmonary nodules, parenchymal consolidation, and bands. Three other groups examined standard VIBE, PET, and CT images. MRI and PET findings were compared to CT using Krippendorff's alpha using patient-based and a lesion-based analysis. Krippendorff's alpha was calculated to assess the interobserver agreement among the three raters of the modified VIBE. RESULTS: In the patient-based analysis (positivity ≥1 lesion), the comparison of modified VIBE with CT showed an alpha of 0.54 for nodules <6 mm (versus 0.41 for standard VIBE and 0.09 for PET) and an alpha of 0.88 for nodules ≥6 mm (versus 0.74 for standard VIBE and 0.42 for PET). On a lesion-based analysis (presence/absence of each lesion), modified VIBE compared to CT showed an alpha of0.58 for nodules <6 mm (versus 0.44 for standard VIBE and 0.09 for PET) and an alpha of 0.90 for nodules ≥6 mm (versus 0.79 for standard VIBE and 0.50 for PET). The alpha value for the interobserver agreement was 0.90 for nodules <6 mm, 0.91 for nodules ≥6 mm, 1.00 for consolidations, and 0.95 for bands in the patient-based analysis and 0.89, 0.93, 1.00, and 0.95 in the lesion-based analysis. CONCLUSIONS: Modified VIBE proved to be reproducible, showed better accuracy than standard VIBE and PET, and very good concordance with CT in assessing lung nodules ≥6 mm, whereas the agreement was less satisfactory for smaller nodules.

Intrapartum group B Streptococcus screening in the labor ward by Xpert® GBS real-time PCR.

Group B Streptococcus (GBS) is the leading cause of neonatal infections in industrialized countries. Intrapartum antibiotic prophylaxis (IAP) given to colonized parturients is a key step for the prevention of neonatal early-onset infection. We compared the performances of Xpert® GBS polymerase chain reaction (PCR) (Cepheid, Sunnyvale, CA, USA) as a point-of-care system in labor wards to standard culture for intrapartum GBS detection. Pregnant women with a GBS-positive antenatal screening were prospectively included. A vaginal double swab was collected at the time of delivery for point-of-care Xpert® GBS PCR and GBS culture. A total of 565 pregnant women were included. Valid Xpert® GBS results were obtained for 488 (86.4%) women on the first attempt. Repeat testing improved the PCR success to 516 (91.3%) women. Among the 305 women positive for GBS by culture at delivery, only 238 (78.0%) were positive by Xpert® GBS PCR, cycle thresholds being correlated to culture quantification. Among 260 women negative for GBS culture, 56 (21.5%) were positive by Xpert® GBS PCR, including 50 where IAP was initiated before vaginal sampling. Overall, among the 565 women with GBS antenatal positive culture, only 335 (59.3%) were still positive at delivery whatever the technique used, resulting in unnecessary IAP for 40% of them. This large cohort study comparing intrapartum to antepartum GBS detection provides evidence that (i) Xpert® GBS PCR might be a valuable solution for intrapartum GBS detection compared to culture-based strategies and (ii) laboratory training of non-specialized staff is mandatory to reach the performances required for point-of-care tests.

Risk factors including the presence of inflammation at the resection margins for colorectal anastomotic stenosis following surgery for diverticular disease.

AIM: The aim of this study was to investigate risk factors for anastomotic stenosis in patients operated on for diverticular disease. Histological inflammation and diverticula at the resection margins were also considered. METHOD: Patients' characteristics, the surgical technique and postoperative complications were collected from the medical records. Anastomotic stenoses were evaluated prospectively by rigid sigmoidoscopy during follow-up examination. Histological specimens were examined by a single pathologist who investigated inflammation and diverticula at the resection margins. Twenty patients with anastomotic colorectal stenosis from a single tertiary centre were compared with 24 consecutive patients without stenosis. They were all operated on for diverticular disease over a specified time period. RESULTS: Histological inflammation and diverticula were found in 25% and 30% of the resection margins respectively. Univariate analysis showed that age > 71 years (P = 0.0002), female gender (P = 0.0069) and anastomoses located below 12 cm from the anal verge (P = 0.020) were risk factors for stenosis. No correlation was found between anastomotic stenosis and the presence of histological inflammation or diverticula at the resection margins. By multivariate analysis, only age > 71 years was found to be a statistically significant risk factor for stenosis (P = 0.0003, OR = 60.8, 95% CI: 6.4-575.5). CONCLUSION: Anastomotic stenosis is a frequent, long-term complication following surgery for diverticular disease. An analysis demonstrated that age is a risk factor for colorectal stenosis and that histological inflammation and the presence of diverticula near/at the resection margins have no effect on the incidence of stenosis.

Influence of health locus of control and fear of hypoglycaemia on glycaemic control and treatment satisfaction in people with Type 1 diabetes on insulin pump therapy.

AIM: To assess the influence of health locus of control and fear of hypoglycaemia on metabolic control and treatment satisfaction in people with Type 1 diabetes mellitus on continuous subcutaneous insulin infusion. METHODS: People with Type 1 diabetes on continuous subcutaneous insulin infusion for at least 1 year, sub-classified as an 'acceptable glucose control' group [HbA1c ≤ 58 mmol/mol (7.5%)] and a 'suboptimum glucose control' group [HbA1c > 58 mmol/mol (7.5%)], were consecutively enrolled in a multicentre cross-sectional study. Questionnaires were administered to assess health locus of control [Multidimensional Health Locus of Control (MHLC) scale, with internal and external subscales], fear of hypoglycaemia [Hypoglycaemia Fear Survey II (HFS-II)] and treatment satisfaction [Diabetes Treatment Satisfaction Questionnaire (DTSQ)]. RESULTS: We enrolled 214 participants (mean ± sd age 43.4 ± 12.1 years). The suboptimum glucose control group (n = 127) had lower mean ± sd internal MHLC and DTSQ scores than the acceptable glucose control group (19.6 ± 5.2 vs 21.0 ± 5.0, P = 0.04 and 28.8 ± 4.8 vs 30.9 ± 4.5, P < 0.001). HFS-II scores did not differ between the two groups. Internal MHLC score was negatively associated with HbA1c (r = -0.15, P < 0.05) and positively associated with the number of mild and severe hypoglycaemic episodes (r = 0.16, P < 0.05 and r = 0.18, P < 0.001, respectively) and with DTSQ score (r = 0.17, P < 0.05). HFS-II score was negatively associated with DTSQ score (r = -0.18, P < 0.05) and positively with number of severe hypoglycaemic episodes (r = 0.16, P < 0.5). CONCLUSIONS: In adults with Type 1 diabetes receiving continuous subcutaneous insulin infusion, high internal locus represents the most important locus of control pattern for achieving good metabolic control.

First-line screening tests for Cushing's syndrome in patients with adrenal incidentaloma: the role of urinary free cortisol measured by LC-MS/MS.

INTRODUCTION AND AIM: Patients with adrenal incidentaloma present a wide range of cortisol secretion, which is not always properly defined by first-line screening tests recommended to rule out Cushing's syndrome (CS), such as 1-mg dexamethasone suppression test (1-mg DST), late night salivary cortisol (LNSC), or 24-h urinary free cortisol (UFC). Therefore, we examined the diagnostic performance of each screening test in patients with adrenal incidentaloma. MATERIALS AND METHODS: In a series of 164 consecutive patients with adrenal incidentaloma, we measured serum cortisol after 1-mg DST, LNSC, and UFC (with LC-MS/MS). Medical history was investigated for cardiovascular events (CVE) in a subgroup of 93 patients with at least 2 years of follow-up. RESULTS: Serum cortisol <50 nmol/L after 1-mg DST presented the highest sensitivity (100%) to rule out CS, despite a low specificity (62%). UFC > 170 nmol/24 h achieved the highest diagnostic accuracy (sensitivity 98%, specificity 91%, and negative/positive likelihood ratios of 0.02/10.83, respectively). The prevalence of CVE was higher in patients with non-suppressed cortisol after 1-mg DST and high UFC levels (p = 0.018). Traditional cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidemia, BMI > 30 kg/m2, smoke or high gender-based waist circumference) were not associated with CVE. CONCLUSIONS: The 1-mg DST at its lowest threshold presented high sensitivity in identifying CS, but its low specificity encourages us to consider UFC levels, measured with LC-MS/MS, to reduce false-positive test results. High UFC levels could also be considered as markers to stratify cardiovascular risk in patients with adrenal incidentaloma.

Topical tocopherol for treatment of reticular oral lichen planus: a randomized, double-blind, crossover study.

OBJECTIVE: This randomized, double-blind, placebo-controlled crossover study assessed the efficacy of topical tocopherol acetate compared with placebo in easing oral discomfort in patients with reticular oral lichen planus (ROLP). MATERIALS AND METHODS: Thirty-four patients with clinically diagnosed and histologically confirmed ROLP were randomly assigned to two groups, which received first one of two treatments (treatment 1 or 2) for a month, then the other (treatment 2 or 1) for another month, with a two-week washout between them. One treatment contained tocopherol acetate and the other only liquid paraffin. The primary outcome was less discomfort, measured on a visual analog scale (VAS). Secondary outcomes were as follows: length of striae measured and photographed at each follow-up; surface area of lesions; and a modified Thongprasom score. RESULTS: No statistically significant differences emerged between the two treatments (1 vs 2) in terms of VAS scores (P > 0.05; 0.8624) or length of striae (P = 0.0883). Significant differences were seen for surface area of lesions (P < 0.05, P = 0.0045) and modified Thongprasom scores (P = 0.0052). CONCLUSION: The two treatments differed only in terms of the surface area of the lesions and Thongprasom scores, not in VAS scores for discomfort or the length of patients' striae. Topical tocopherol proved effective in the treatment of ROLP.

25-Hydroxycholecalciferol response to single oral cholecalciferol loading in the normal weight, overweight, and obese.

UNLABELLED: After a single cholecalciferol load, peak serum 25-hydroxycholecalciferol (25OHD) is lower in individuals with a higher body mass index (BMI), probably due to it being distributed in a greater volume. Its subsequent disappearance from the serum is slower the higher the individual's BMI, probably due to the combination of a larger body volume and a slower release into the circulation of vitamin D stored in adipose tissue. INTRODUCTION: The aim of the study is to examine 25-hydroxycholecalciferol (25OHD) response to a single oral load of cholecalciferol in the normal weight, overweight, and obese. METHODS: We considered 55 healthy women aged from 25 to 67 years (mean ± SD, 50.8 ± 9.5) with a BMI ranging from 18.7 to 42 kg/m(2) (mean ± SD, 27.1 ± 6.0). The sample was divided into three groups by BMI: 20 were normal weight (BMI ≤ 25 kg/m(2)), 21 overweight (25.1 ≤ BMI ≤ 29.9 kg/ m(2)), and 14 obese (BMI ≥ 30 kg/m(2)). Each subject was given 300,000 IU of cholecalciferol orally during lunch. A fasting blood test was obtained before cholecalciferol loading and then 7, 30, and 90 days afterwards to measure serum 25OHD, 1,25 dihydroxyvitamin D [1,25 (OH)2D], parathyroid hormone (PTH), calcium (Ca), and phosphorus (P). Participants' absolute fat mass was measured using dual energy X-ray absorptiometry (DEXA). RESULTS: The fat mass of the normal weight subjects was significantly lower than that of the overweight, which in turn was lower than that of the obese participants. Serum 25OHD levels increased significantly in all groups, peaking 1 week after the cholecalciferol load. Peak serum 25OHD levels were lower the higher the individuals' BMI. After peaking, the 25OHD levels gradually decreased, following a significantly different trend in the three groups. The slope was similar for the overweight and obese, declining significantly more slowly than in the normal weight group. In the sample as a whole, there was a weakly significant negative correlation between fat mass and baseline 25OHD level, while this correlation became strongly significant at all time points after cholecalciferol loading. CONCLUSIONS: The lower peak 25OHD levels seen in the obese and overweight is probably due to the cholecalciferol load being distributed in a larger body volume. The longer persistence of 25OHD in their serum could be due to both their larger body volume and a slower release into the circulation of the vitamin D stored in their adipose tissue.

Inflammatory cell burden and phenotype in endomyocardial biopsies with antibody-mediated rejection (AMR): a multicenter pilot study from the AECVP.

This multicenter case-controlled pilot study evaluated myocardial inflammatory burden (IB) and phenotype in endomyocardial biopsies (EMBs) with and without pathologic antibody-mediated rejection (pAMR). Sixty-five EMBs from five European heart transplant centers were centrally reviewed as positive (grade 2, n = 28), suspicious (grade 1, n = 7) or negative (n = 30) for pAMR. Absolute counts of total, intravascular (IV) and extravascular (EV) immunophenotyped mononuclear cells were correlated with pAMR grade, capillary C4d deposition, donor specific antibody (DSA) status and acute cellular rejection (ACR). In pAMR+ biopsies, equivalent number of IV CD3+ T lymphocytes (23 ± 4/0.225 mm(2) ) and CD68+ macrophages (21 ± 4/0.225 mm(2) ) were seen. IB and cell phenotype correlated with pAMR grade, C4d positivity and DSA positivity (p < 0.0001). High numbers of IV T lymphocytes were associated with low grade ACR (p = 0.002). In late-occurring AMR EV plasma cells occurring in 34% of pAMR+ EMBs were associated with higher IB. The IB in AMR correlated with pAMR+, C4d positivity and DSA positivity. In pAMR+ equivalent numbers of IV T lymphocytes and macrophages were found. The presence of plasma cells was associated with a higher IB and occurrence of pAMR late after transplantation.

Effect of a single injection of testosterone enanthate on 17ß estradiol and bone turnover markers in hypogonadal male patients.

PURPOSE: Several clinical studies testify the critical role played by estrogens in male bone metabolism. The aim of our study is to assess the effect of a single injection of testosterone enanthate in a group of hypogonadal men on 17ß estradiol serum levels and some bone metabolic parameters. METHOD: Twenty-one hypogonadal males were given one testosterone enanthate injection (250 mg). Blood samples were drawn before the injection and after 1, 2 and 3 weeks. The following variables were measured: Total testosterone (TT), 17ß estradiol (17ß E2), Sex hormone binding globulin, total alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen (CTx). RESULTS: After testosterone injection, both TT and 17ß E2 increased, peaking 1 week after the injection. Individual observation of the response of 17ß E2 to testosterone showed that a subgroup (n = 9) failed to respond with any increase in 17ß E2 at any of the weekly tests (group E2-), while the remainder (n = 12) showed a significant increase in 17ß E2, which reached a mean value three times higher than at baseline (group E2+). The E2- patients reached a TT peak lower than that observed in the E+ group. CTx serum levels declined progressively in the E2+ group, reaching the significance (p = 0.03) at the end of the study, while it did not change in E- group. CONCLUSION: This study suggests that a single injection of testosterone might have different effects on the production of endogenous estrogens, and a significant reduction of bone resorption parameters takes place only in the patients who show a significant increase of 17ß estradiol in response to testosterone administration.

Intraplaque hemorrhage in cardiac allograft vasculopathy.

Plaque hemorrhage, inflammation and microvessel density are key determinants of plaque vulnerability in native coronary atherosclerosis (ATS). This study investigates the role of intraplaque hemorrhage (IPH) and its relation with inflammation and microvessels in cardiac allograft vasculopathy (CAV) in posttransplanted patients. Seventy coronary plaques were obtained from 12 patients who died because of CAV. For each patient we collected both native heart and the allograft, at the time of transplantation and autopsy, respectively. Intralesion inflammation, microvessels and IPH were assessed semi-quantitatively. IPH was observed in 21/35 (60%) CAV lesions and in 8/35 (22.9%) native ATS plaques, with a strong association between fibrocellular lesions and IPH (p = 0.0142). Microvessels were detected in 26/35 (74.3%) of CAV lesions with perivascular leakage as sign of endothelial damage in 18/26 (69.2%). IPH was strongly associated with microvessels (p < 0.0001). Inflammation was present in 31/35 (88.6%) of CAV lesions. CAV IPH+ lesions were characterized by presence of both fresh and old hemorrhage in 12/21 (57.1%). IPH, associated with microvessel damage and inflammation, is an important feature of CAV. Fresh and old intralesion hemorrhage suggests ongoing remodeling processes promoting the lesion progression and vulnerability.

Is resectable hepatocellular carcinoma a contraindication to liver transplantation? A novel decision model based on "number of patients needed to transplant" as measure of transplant benefit.

BACKGROUND & AIMS: Number-needed-to-treat is used in assessing the effectiveness of a health-care intervention, and reports the number of patients who need to be treated to prevent one additional bad outcome. Although largely used in medical literature, there are no studies measuring the benefit of liver transplantation (LT) over hepatic resection (HR) for hepatocellular carcinoma (HCC) in terms of "Number of patients needed to transplant (NTT)." EXCLUSION CRITERIA: Child-Turcotte-Pugh (CTP) Classes B-C, very large (>10 cm) and multi-nodular (>2 nodules) tumours, macroscopic vascular invasion and extra-hepatic metastases. STUDY POPULATION: 1028 HCC cirrhotic patients from one Eastern (n=441) and two Western (n=587) surgical units. Patient survival observed after HR by proportional hazard regression model was compared to that predicted after LT by the Metroticket calculator. The benefit obtainable from LT compared to resection was analysed in relationship with number of nodules (modelled as ordinal variable: single vs. oligonodular), size of largest nodule (modelled as a continuous variable), presence of microscopic vascular invasion (MVI), and time horizon from surgery (5-year vs. 10-year). RESULTS: 330 patients were beyond the Milan criteria (32%) and 597 (58%) had MVI. The prevalence of MVI was 52% in patients within Milan criteria and 71% in those beyond (p<0.0001). In the 5-year transplant benefit analysis, nodule size and HCC number were positive predictors of transplant benefit, while MVI had a strong negative impact on NTT. Transplantation performed as an effective therapy (NTT <5) only in oligonodular HCC with largest diameter >3cm (beyond conventional LT criteria) when MVI was absent. The 10-year scenario increased drastically the transplant benefit in all subgroups of resectable patients, and LT became an effective therapy (NTT <5) for all patients without MVI whenever tumor extension and for oligonodular HCC with MVI within conventional LT criteria. CONCLUSIONS: Based on NTT analysis, the adopted time horizon (5-year vs. 10-year scenario) is the main factor influencing the benefit of LT in patients with resectable HCC and Child A cirrhosis.

Characterization of the anisotropic mechanical behaviour of colonic tissues: experimental activity and constitutive formulation.

The aim was to investigate the biomechanical behaviour of colonic tissues by a coupled experimental and numerical approach. The wall of the colon is composed of different tissue layers. Within each layer, different fibre families are distributed according to specific spatial orientations, which lead to a strongly anisotropic configuration. Accounting for the complex histology of the tissues, mechanical tests must be planned and designed to evaluate the behaviour of the colonic wall in different directions. Uni-axial tensile tests were performed on tissue specimens from 15 fresh pig colons, accounting for six different loading directions (five specimens for each loading direction). The next step of the investigation was to define an appropriate constitutive framework and develop a procedure for identification of the constitutive parameters. A specific hyperelastic formulation was developed that accounted for the multilayered conformation of the colonic wall and the fibre-reinforced configuration of the tissues. The parameters were identified by inverse analyses of the mechanical tests. The comparison of model results with experimental data, together with the evaluation of satisfaction of material thermomechanics principles, confirmed the reliability of the analysis developed. This work forms the basis for more comprehensive activities that aim to provide computational tools for the interpretation of surgical procedures that involve the gastrointestinal tract, considering the specific biomedical devices adopted.

Combination therapy for Cushing's disease: effectiveness of two schedules of treatment: should we start with cabergoline or ketoconazole?

Cushing's disease (CD) is associated with increased morbidity and mortality. Until now, no medical treatment has been shown to be totally satisfactory when administrated alone. This study aimed to assess the effectiveness of cabergoline with added ketoconazole and of the same combination in reverse, using urinary free cortisol (UFC) and late night salivary cortisol (LNSC) levels as biochemical markers of the treatments' efficacy in CD patients. A prospective analysis conducted on 14 patients (f/m = 12/2; median age 52, range 33-70 years) divided into two groups: 6 patients initially treated with cabergoline for 4-6 months (rising from 0.5-1 mg/week up to 3.0 mg/week), after which ketoconazole was added (group A); and 8 patients first took ketoconazole alone for 4-6 months (rising from 200 mg/day to 600 mg/day), then cabergoline was added (group B). Patients were compared with 14 age-matched patients in prolonged remission after effective neurosurgery for CD. The combination therapy led to UFC normalization in 79 % of patients with no differences between the groups; only one patient failed to respond at all. Neither drug succeeded in controlling the disease when taken alone. LNSC dropped when compared to baseline levels, but not to a significant degree (p = 0.06), and it remained significantly higher than in controls (p = 0.0006). Associating cabergoline with ketoconazole may represent an effective second-line treatment, achieving a satisfactory reduction in UFC levels and clinical improvement. Although the combined treatment lowered patients' LNSC levels, they remained higher than normal, indicating a persistent subclinical hypercortisolism; the implications of this condition need to be considered. No differences emerged between the two treatment schedules.

Thrombin generation in Cushing's Syndrome: do the conventional clotting indices tell the whole truth?

Cushing's Syndrome (CS) is associated with an increased mortality, where hypercoagulability seems to have a crucial role in both arterial and venous thrombosis. Parameters of in vitro thrombin generation (TG) such as lag time, peak thrombin and endogenous thrombin potential (ETP), that describe the time until thrombin burst, the peak amount of TG and the total amount of thrombin generated, respectively as well as classical clotting markers were evaluated in 33 CS patients compared to both a group of 28 patients matched for the features of Metabolic Syndrome (MetS) and 31 healthy individuals. CS and MetS patients had shorter lag time (p < 0.0001), higher peak and ETP (p < 0.0001) than healthy controls, though lag time was less shortened in CS (p < 0.0001) respect to MetS group. Prothrombin time (PT) was increased (p < 0.0001) in both CS and MetS patients, while partial thromboplastin time (PTT) was shorter (p < 0.0001) in CS compared to both MetS and healthy group (p < 0.0001). Factor VIII (FVIII), Antithrombin (AT), protein C and S were increased only in CS patients (p < 0.0001). lag time, AT and FVIII correlated to night salivary cortisol (r = + 0.59; p = 0.0005, r = + 0.40; p = 0.003, r = + 0.40; p = 0.04, respectively); PTT correlated inversely to urinary free cortisol (r = -0.45; p = 0.009). BMI correlated negatively to lag time (r = -0.40; p = 0.0001) and positively to peak and ETP (r = + 0.34; p = 0.001, r = + 0.28; p = 0.008, respectively). Obese and diabetic patients had shorter lag time (p = 0.0005; p = 0.0002, respectively), higher ETP (p = 0.0006; p = 0.007, respectively) and peak (p = 0.0003; p = 0.0005, respectively) as well as a more prolonged PT (p = 0.04; p = 0.009, respectively). Hypertensive individuals had higher ETP (p = 0.004), peak (p = 0.0008) and FVIII (p = 0.001). Our findings confirm a prothrombotic state in both CS and MetS patients, though lag time was less shortened in CS. The high levels of endogenous physiological anticoagulants, could possibly represent a protective mechanism against hypercoagulability seen in CS patients.

Potential use of contrast-enhanced ultrasound (CEUS) in the detection of metastatic superficial lymph nodes in melanoma patients.

PURPOSE: Malignant melanoma represents a significant and growing public health burden worldwide. Ultrasonography is the most useful diagnostic modality for regional lymph nodal staging. Because any focal areas of cortical lobulation or thickening-swelling should also be considered as a sign of metastases, we are going to report the usefulness of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign or malignant lymph nodes in patients with malignant melanoma based on blood stream patterns and investigate the diagnostic capability. PATIENTS AND METHODS: After the excision of cutaneous melanoma with positive excision margins but with negative sentinel lymph node, 540 patients underwent US of superficial lymph nodes. The inclusion criteria for CEUS consisted of both major signs (absence of the echogenic hilus, round shape, and peripheral capsular vascularity) and minor ones (the presence of focal cortical thickening). The diagnostic capability was evaluated by comparing the cytological findings with the enhancement pattern on CEUS.  RESULTS: US in combination with CEUS correctly classified 534/540 patients. CEUS applied to lymph nodes with focal cortical thickening on grayscale US confirmed great sensitivity (0.98) and specificity (0.99) but above all, it showed a markedly improved accuracy of 0.99. The likelihood ratios confirmed the good performance of the methods used. CONCLUSION: CEUS increases the diagnostic accuracy of US in the differential diagnosis of benign and malignant LNs but it also allows us, when possible, to avoid unnecessary invasive operations such as LN FNAC. Moreover, CEUS may guide FNAC in the case of focal cortical thickening on the basis of hypoperfusion, with a reduction in the number of false negatives and much earlier detection of nodal metastatic foci.

In young men sperm telomere length is related to sperm number and parental age.

STUDY QUESTION: What are the relationships between telomere lengths in leukocytes and sperm, sperm count and parents' age at conception in a group of apparently healthy subjects of the same age? SUMMARY ANSWER: Sperm telomere length (STL) is related to sperm count, it is lower in oligozoospermic than in normozoospermic men and it is directly related to parents' age at conception. WHAT IS KNOWN ALREADY: Leukocyte telomere length (LTL) decreases with age but STL increases and offspring of older fathers tend to have longer leukocyte telomeres. Only one study analyzed STL in relation to male fertility, and reported shorter telomeres in infertile versus fertile men. No data have been reported on STL in relation to parents' age at conception. STUDY DESIGN, SIZE, DURATION: Prospective study conducted from January to December 2012 of 18-19-year-old high school students. PARTICIPANTS/MATERIALS, SETTING AND METHODS: The volunteers were 81 apparently healthy subjects, including 61 with normozoospermia and 20 with idiopathic oligozoospermia. Leukocyte and sperm telomere length were measured by real-time PCR. Data were analyzed for determining the relationships between LTL, STL, sperm count and parents' age at conception. MAIN RESULTS AND THE ROLE OF CHANCE: Sperm and leukocyte telomere length were strongly correlated, but STL was significantly longer. A significant positive correlation between STL and total sperm number was found. STL was significantly lower in oligozoospermic than in normozoospermic men. Finally, we found a significant positive relationship between maternal age and both leukocyte and sperm telomere length and a significant positive relation between paternal age and STL in the offspring. The relative contributions of mothers' and fathers' ages to their offspring's telomere length could not be determined because of the high correlation between paternal and maternal ages. LIMITATIONS AND REASONS FOR CAUTION: Although consistent with previous findings, this is the first study on telomere length in oligo- and normozoospermic men and included a relatively low number of subjects. Our study was also restricted to young (18-19 year old) men, so future studies should determine whether our findings can be generalized to men at ages typically encountered at fertility centers. Future studies should also try to determine the possible effect of abstinence time and frequency of ejaculation with STL. WIDER IMPLICATIONS OF THE FINDINGS: Our study sheds new light on the association between STL and sperm count and on the inheritance of telomere length (in leukocytes and sperm) in relation to the parents' age at conception. Additional studies are needed to confirm these observations, to clarify if the association between shorter STL and damaged spermatogenesis represents a pathophysiological link, and to determine the effect on offspring telomere length of assisted reproduction techniques performed on couples of advanced age or where the man is oligozoospermic. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Italian Ministry of University and Research (grant no. 2009AMPA9C to C.F.) and Padova University (grant 2010 to A.D.R.). The authors have no competing interests to declare.

Venous thromboembolism in patients with Cushing's syndrome: need of a careful investigation of the prothrombotic risk profile.

A high incidence of venous thromboembolic (VTE) complications has been reported in Cushing's syndrome (CS), mostly post-operatively and attributable to hypercoagulability. The prevalence of symptomatic VTE was investigated retrospectively in 58 consecutive CS patients in relation to acquired and genetic thrombotic risk factors. Eight CS patients (14 %) developed VTE (group A), 3 of them related and 5 unrelated to surgery. These patients had higher urinary free cortisol (p = 0.01) and VWF levels (p = 0.02) than the 50 patients without VTE (group B), as well an increase in the hemostatically more efficient, high-molecular-weight VWF multimers (p = 0.002). Factor V Leiden and the prothrombin gene 20210A variants (the most common inherited thrombophilic defects) were more represented in group A than in group B, as was the genotype GCAG/GCAG of the VWF gene promoter, known to hyperinduce VWF upregulation under cortisol excess. All but one of the patients with VTE unrelated to surgery had at least four acquired and at least one inherited risk factor. Severe hypercortisolism and VWF levels with increased haemostatic activity are strongly associated with VTE in CS. VTE episodes unrelated to surgery are attributable to the synergistic action of acquired and inherited thrombotic risk factors. Based on these observations, we believe that severely affected CS patients should be screened for coagulation disorders and receive antithrombotic prophylaxis whenever they have concomitant prothrombotic risk factors.

Anthropometric, penile and testis measures in post-pubertal Italian males.

BACKGROUND: Relationships between anthropometric measures, body proportions, weight and penile dimensions in young adult males have not been previously analyzed. Furthermore, although male fertility has declined in last decades, no data on testicular volume (the best surrogate measure for spermatogenic potential) are available for the general population of young men in Italy. AIM: To analyze anthropometric measures and proportions, testicular volumes, and penile dimensions in a large cohort from the general population of young Italian men aged 18-19 yr. MATERIALS/SUBJECTS: We analyzed 2019 students aged 18-19 years for height, weight, body mass index (BMI), waist circumference, arm span, pubis-to-floor and crown-to-pubis length, and penile dimensions. Testicular volumes were measured by ultrasound in 776 subjects. RESULTS: Thirty-six percent of the subjects had a pathological arm span-height difference (>3 cm) and 44.7% had a pathological pubis-to-floor/ crown-to-pubis ratio (≤ 0.92). The mean penis length was 8.9 ± 1.4 cm and the penis circumference was 9.5 ± 1.0 cm. BMI was positively associated with arm span-height difference and negatively with penis length; 23.2% of the subjects had low mean testicular volume (<12 ml). CONCLUSIONS: The findings highlight a strong influence of BMI on skeletal proportions and penis length, identify a large proportion of subjects with testicular hypotrophy at risk for future fertility, and suggest to consider worldwide studies to redefine normal values for arm span-height difference and upper/ lower body segment ratio.

Human olfactory sensitivity for bourgeonal and male infertility: a preliminary investigation.

Olfactory receptor (OR) expression is also present in the sperm cells and could mediate sperm chemotaxis. OR1D2 was the first OR expressed in the testis demonstrated to be involved in chemotaxis and to be expressed also in the nose with a similar behavior. Bourgeonal is the OR1D2 most potent known agonist. Infertility affects ~15 % of couples in western countries and sometimes it is unexplained. This pilot study compared the bourgeonal olfactory thresholds, the ability of sperm to sense the bourgeonal and the frequency of 13 single nucleotide polymorphisms (SNPs) of OR1D2 gene in nine males suffering of unexplained infertility with a control group of 15 healthy males. The mean olfactory threshold for bourgeonal was statistically different between the study group (10.5 ± 3.7; median 12.3) and the control group (14.0 ± 2.8; median 15.5) (p = 0.006). Statistical analysis showed a significantly higher percentage of spermatozoa that migrated toward the capillaries filled with bourgeonal in the control group compared to the study group (p < 0.0001). Sperm migration was equally inhibited in both groups of subjects when, together with bourgeonal, capillaries were filled with undecanal, a strong bourgeonal inhibitor (p = 0.42). The 13 SNPs of OR1D2 revealed a statistically significant difference for allele and genotype frequency of rs769423 in study group versus control group (p = 0.02). The present preliminary study seems to confirm the important role of OR1D2 both in nose and spermatozoa and may explain the idiopathic infertility of the study group. Further studies on larger series are mandatory to confirm our preliminary evidence.