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Background: The glucosuria induced by sodium-glucose cotransporter-2 inhibitors (SGLT2i) stimulates endogenous (hepatic) glucose production (EGP) blunting the decline in HbA1c. We hypothesized that, in response to glucosuria, a renal signal is generated and stimulated EGP. Aim: To examine the effect of acute administration of dapagliflozin (DAPA) in nondiabetic, renal transplant subjects on SGLT2i-induced stimulation of EGP. Methods: 20 subjects [10 with intact native kidneys (IK) and 10 with bilateral nephrectomy (NK)] underwent measurement of EGP ([6,6-2H2]-glucose) before and for 6 hours after administration of DAPA or placebo (PLC) on 2 separate days. Results: DAPA induced greater glucosuria in subjects with IK versus NK (8.6±1.1 vs. 5.5±0.5 grams/6-hrs; p=0.02). During 6-hour, plasma glucose decreased slightly and similarly in both groups, with no difference compared to PLC. Following PLC, there was a progressive time-related decline in EGP that was similar in both groups. Following DAPA, EGP declined in both groups but the decrement in EGP was 56% greater in the NK. During DAPA, urinary glucose excretion was correlated with EGP (r = 0.34, p Conclusions: In NK subjects the hepatic compensatory response to acute SGLT2i-induced glucosuria was attenuated compared to diabetic subjects with IK, suggesting a SGLT2i-mediated stimulation of hepatic glucose production via efferent renal nerves in an attempt to compensate for the urinary glucose loss, i.e., a renal-hepatic axis. Disclosure G. Daniele: None. C. Solis-Herrera: Consultant; Self; Lexicon Pharmaceuticals, Inc. A. Dardano: None. A. Mari: Consultant; Self; Lilly Diabetes. Research Support; Self; Boehringer Ingelheim International GmbH. A. Tura: None. L. Giusti: None. J.J. Kurumthodathu: None. A.A.G. Brocchi: None. B. Campi: None. A. Saba: None. A. Bianchi: None. C. Tregnaghi: None. M. Egidi: None. M. Abdul-Ghani: None. R.A. DeFronzo: None. S. DelPrato: None.

Aims/hypothesis The glucosuria induced by sodium–glucose cotransporter 2 (SGLT2) inhibition stimulates endogenous (hepatic) glucose production (EGP), blunting the decline in HbA1c. We hypothesised that, in response to glucosuria, a renal signal is generated and stimulates EGP. To examine the effect of acute administration of SGLT2 inhibitors on EGP, we studied non-diabetic individuals who had undergone renal transplant with and without removal of native kidneys. Methods This was a parallel, randomised, double-blind, placebo-controlled, single-centre study, designed to evaluate the effect of a single dose of dapagliflozin or placebo on EGP determined by stable-tracer technique. We recruited non-diabetic individuals who were 30–65 years old, with a BMI of 25–35 kg/m2 and stable body weight (±2 kg) over the preceding 3 months, and HbA1c Results Twenty non-diabetic renal transplant patients (ten with residual native kidneys, ten with bilateral nephrectomy) participated in the study. Dapagliflozin induced greater glucosuria in individuals with residual native kidneys vs nephrectomised individuals (8.6 ± 1.1 vs 5.5 ± 0.5 g/6 h; p = 0.02; data not shown). During the 6 h study period, plasma glucose decreased only slightly and similarly in both groups, with no difference compared with placebo (data not shown). Following administration of placebo, there was a progressive time-related decline in EGP that was similar in both nephrectomised individuals and individuals with residual native kidneys. Following dapagliflozin administration, EGP declined in both groups, but the differences between the decrement in EGP with dapagliflozin and placebo in the group with bilateral nephrectomy (Δ = 1.11 ± 0.72 μmol min−1 kg−1) was significantly lower (p = 0.03) than in the residual native kidney group (Δ = 2.56 ± 0.33 μmol min−1 kg−1). In the population treated with dapagliflozin, urinary glucose excretion was correlated with EGP (r = 0.34, p Conclusions/interpretation In nephrectomised individuals, the hepatic compensatory response to acute SGLT2 inhibitor-induced glucosuria was attenuated, as compared with individuals with residual native kidneys, suggesting that SGLT2 inhibitor-mediated stimulation of hepatic glucose production via efferent renal nerves occurs in an attempt to compensate for the urinary glucose loss (i.e. a renal–hepatic axis). Trial registration ClinicalTrials.gov NCT03168295 Funding This protocol was supported by Qatar National Research Fund (QNRF) Award No. NPRP 8-311-3-062 and NIH grant DK024092-38. Graphical abstract

Cerebrovascular accidents (CVA) represent a major complication in diabetes (DM). Real-life evidence as to whether modern management of CVA and DM have softened this relationship is currently limited. We assessed the prevalence of DM, previously known or newly-diagnosed, in all patients (N=542, males 51.5%) admitted for CVA at the Stroke Unit (SU) of Verona University Hospital from 1/1/2015 to 12/31/2016. DM was ascertained by previous diagnosis, glucose-lowering therapy at admission/discharge or admittance plasma glucose (PG) ≥11.1 mmol/L. Prevalence of DM was 21.03% (78.1% known-DM; 21.9% new-DM). In-hospital death rate was 10.5%. Compared to non-DM, patients with DM showed an increased risk of death (15.8 vs. 9.1%; OR 1.87 95% CI, 1.03-3.41) and complications (48.2 vs. 33.3%; 1.87, 1.22-2.86) with similar duration of hospitalization (mean±SEM, 9.14±1.06 vs. 8.80±0.39 days, p=0.72). All deaths occurred in the SU. The “survivors” with DM transferred to non-intensive ward had an out-of-SU hospital stay twice as longer than non-DM (2.32±1.02 vs. 0.98±0.19 days, p=0.038). After multivariable adjustment, DM remained predictor of complications (adj-OR 1.87, 1.22-2.86) but not mortality (1.79, 0.92-3.46). Patients in the highest PG quartile (≥6.55 mmol/L) displayed the highest risk of death (7.89, 2.73-22.79; PG In conclusion, these data highlight that DM frequently occurs in patients admitted for CVA and adds an excess burden of adverse clinical outcomes that urgently calls for strategies to anticipate DM diagnosis in high-risk individuals. Disclosure M. Dauriz: None. E. Tregnaghi: None. L. Santi: None. T. Lucianer: None. A. Altomari: None. E. Rinaldi: None. S. Tardivo: None. C. Bovo: None. E. Bonora: None.

Objective In patients with a history of lymphoma, each lymphadenopathy should be carefully evaluated. The aims of this study were to evaluate (i) the usefulness of high-resolution ultrasonography (US), US-guided fine-needle aspiration cytology (FNAC) and flow cytometry phenotyping (FCP) together in the diagnosis of recurrent lymphoma, and (ii) whether these tools were independent predictors of correct results. Design Retrospective cohort study with stepwise forward logistic regression analysis of results. Setting Tertiary referral centre. Participants A total of 151 patients with history of lymphoma who developed a cervical mass during follow-up. Methods On neck US, a lymphadenopathy was shown in 129 (85.4%) patients (median age 57 years, range 18-78 years), and US-guided FNAC combined with FCP were immediately performed. All patients had surgical excision and subsequent histological examination of the enlarged node(s), to establish lymphoma subclassification. Results Final histology confirmed recurrence in 82 (63.6%) patients. According to the logistic regression analysis, FNAC and FCP were independent predictors of correct results (p=0.009 and 0.028, respectively) and did not interfere with each other. The sensitivity, specificity and accuracy of the combination of all of the tools were 98.8%, 100%, and 99.2%, respectively, and the area under the receiver operating characteristic curve was 0.902 (95% CI: 0.797-0.896). Conclusion This minimally-invasive procedure is easily performed and should be recommended for all patients with cervical lymphadenopathy and a history of lymphoma, avoiding the need of core-biopsy or surgical excision if recurrence was excluded. This article is protected by copyright. All rights reserved.

Summary Background Patients who are immunocompromised because of malignancy have an increased risk of herpes zoster and herpes zoster-related complications. We aimed to investigate the efficacy and safety of an inactivated varicella zoster virus (VZV) vaccine for herpes zoster prevention in patients with solid tumour or haematological malignancies. Methods This phase 3, two-arm, randomised, double-blind, placebo-controlled, multicentre trial with an adaptive design was done in 329 centres across 40 countries. The trial included adult patients with solid tumour malignancies receiving chemotherapy and those with haematological malignancies, either receiving or not receiving chemotherapy. Patients were randomly assigned (1:1) to receive four doses of VZV vaccine inactivated by γ irradiation or placebo approximately 30 days apart. The patients, investigators, trial site staff, clinical adjudication committee, and sponsor's clinical and laboratory personnel were masked to the group assignment. The primary efficacy endpoint was herpes zoster incidence in patients with solid tumour malignancies receiving chemotherapy, which was assessed in the modified intention-to-treat population (defined as all randomly assigned patients who received at least one dose of inactivated VZV vaccine or placebo). The primary safety endpoint was serious adverse events up to 28 days after the fourth dose in patients with solid tumour malignancies receiving chemotherapy. Safety endpoints were assessed in all patients who received at least one dose of inactivated VZV vaccine or placebo and had follow-up data. This trial is registered ( NCT01254630 and EudraCT 2010-023156-89). Findings Between June 27, 2011, and April 11, 2017, 5286 patients were randomly assigned to receive VZV vaccine inactivated by γ irradiation (n=2637) or placebo (n=2649). The haematological malignancy arm was terminated early because of evidence of futility at a planned interim analysis; therefore, all prespecified haematological malignancy endpoints were deemed exploratory. In patients with solid tumour malignancies in the modified intention-to-treat population, confirmed herpes zoster occurred in 22 of 1328 (6·7 per 1000 person-years) VZV vaccine recipients and in 61 of 1350 (18·5 per 1000 person-years) placebo recipients. Estimated vaccine efficacy against herpes zoster in patients with solid tumour malignancies was 63·6% (97·5% CI 36·4 to 79·1), meeting the prespecified success criterion. In patients with solid tumour malignancies, serious adverse events were similar in frequency across treatment groups, occurring in 298 (22·5%) of 1322 patients who received the vaccine and in 283 (21·0%) of 1346 patients who received placebo (risk difference 1·5%, 95% CI −1·7 to 4·6). Vaccine-related serious adverse events were less than 1% in each treatment group. Vaccine-related injection-site reactions were more common in the vaccine group than in the placebo group. In the haematological malignancy group, VZV vaccine was well tolerated and estimated vaccine efficacy against herpes zoster was 16·8% (95% CI −17·8 to 41·3). Interpretation The inactivated VZV vaccine was well tolerated and efficacious for herpes zoster prevention in patients with solid tumour malignancies receiving chemotherapy, but was not efficacious for herpes zoster prevention in patients with haematological malignancies. Funding Merck & Co, Inc.

We present an application of the Industry 4.0 enabling technologies to Bottega Veneta, an Italian luxury goods house renowned in the world for its leather goods. In particular, we address the production process throughout the supply chain. The proposed framework introduces a uniform data model, used by all the actors involved in the production process to collect and represent the large amount of data involved in the production process. A DSS (Decision Support System) allows the production planner to focus on different scenarios to take better decisions.

Summary Objectives This phase III study assessed the safety and immunogenicity of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, administered with routine vaccines starting at 2 months of age. Methods Healthy infants received MenACWY-CRM in a two- or three-dose primary infant series plus a single toddler dose. In addition, a two-dose toddler catch-up series was evaluated. Immune responses to MenACWY-CRM were assessed for serum bactericidal activity with human complement (hSBA). Reactogenicity and safety results were collected systematically. Results After a full infant/toddler series or two-dose toddler catch-up series, MenACWY-CRM elicited immune responses against the four serogroups in 94–100% of subjects. Noninferiority of the two- versus three-dose MenACWY-CRM infant dosing regimen was established for geometric mean titers for all serogroups. Following the three-dose infant primary series, 89–98% of subjects achieved an hSBA ≥8 across all serogroups. Immune responses to concomitant routine vaccines given with MenACWY-CRM were noninferior to responses to routine vaccines alone, except for pertactin after the two-dose infant series. Noninferiority criteria were met for all concomitant antigens after the three-dose infant series. Conclusions MenACWY-CRM vaccination regimens in infants and toddlers were immunogenic and well tolerated. No clinically meaningful effects of concomitant administration with routine infant and toddler vaccines were observed.

Objective To compare clinical evaluation, transvaginal sonography (TVS), saline contrast sonovaginography (SCSV) and magnetic resonance imaging (MRI) in the diagnosis of posterior deep pelvic endometriosis (DPE). Methods Women suspected of having posterior DPE on the basis of subjective symptoms and clinical evaluation underwent digital vaginal and rectal examination, TVS, SCSV and MRI. Laparoscopy was performed and specimens were sent for histological examination. Sensitivity, specificity, positive and negative predictive value, as well as positive and negative likelihood ratios were analyzed for each diagnostic method. Results Fifty-four out of 102 women suspected of having posterior DPE underwent laparoscopic surgery. Among these, in 46 (85.2%) cases DPE was confirmed at laparoscopic and histological examination. SCSV correctly identified 43 (93.5%) cases, presenting higher accuracy than did the other procedures. SCSV and MRI were more accurate in diagnosing and discriminating between the different locations of endometriotic lesions, with respective sensitivities of 94.7 and 73.1% for vaginal fornix, 88.9 and 66.7% for the uterosacral ligaments and 80.6 and 83.3% for involvement of the rectovaginal septum. The specificity of SCSV and MRI, respectively, was 97.1 and 94.3% for vaginal fornix, 95.6 and 95.6% for uterosacral ligaments and 100 and 77.8% for involvement of the rectovaginal septum. In the diagnosis of rectal endometriosis, we found a sensitivity of 66.7% for both techniques and specificity of 93.8% for SCSV and 95.8% for MRI. Conclusion TVS should be used as the first-line diagnostic technique and SCSV and/or MRI as second-line methods in the diagnosis of posterior DPE. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Objective To assess antibody persistence after vaccination with a new, fully liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine at 18 months of age versus licensed DTaP-IPV//PRP-T and hepatitis B (Hep B) vaccines, and to assess the immunogenicity and safety of a subsequent DTaP-IPV//PRP-T booster. Methods A phase III, open-label, single-center study was conducted. Infants previously primed with 3 doses of DTaP-IPV-Hep B-PRP-T (Hexaxim: N = 232 [group 1]) or DTaP-IPV//PRP-T and hepatitis B vaccine (Pentaxim + Engerix B Pediatrico: N = 226 [group 2]) at 2, 4, and 6 months of age received a DTaP-IPV//PRP-T booster at 18 months of age. Antibodies were measured before and 1 month after booster vaccination. Safety was evaluated from parental reports. Analyses were descriptive. Results Antibody persistence was high and similar in each group for each antigen except for Hep B, for which the percentage (95% confidence interval) of participants with a titer of ≥ 10 mIU/mL was higher in group 2 (99.5% [97.5%, 100.0%]) than in group 1 (85.5% [80.3%, 89.8%]). Postbooster seroprotection (diphtheria, tetanus, inactivated poliovirus, polyribosyl-ribitol phosphate) and serconversion (pertussis toxoid, filamentous hemagglutinin) rates were high and similar in each group, and geometric mean antibody concentrations increased markedly in both groups. Safety after the booster vaccination was good and independent of the primary-series vaccine, although one serious adverse event of convulsions was considered to be vaccine related. Conclusions The DTaP-IPV/PRP-T booster vaccination at 18 months of age was similarly immunogenic and well tolerated after primary-series vaccination with either the investigational hexavalent vaccine or the reference pentavalent vaccine. This confirms the suitability of a booster vaccination of DTaP-IPV//PRP-T after a primary series of the new DTaP-IPV-Hep B-PRP-T vaccine.

The aim was to determine whether the immunogenicity of an investigational hepatitis B vaccine (spHB) is at least as high as that of a licensed control vaccine, Engerix B, and to evaluate its safety before inclusion in new pediatric combination vaccines. Two randomized, controlled, blind-observer, Phase 3 trials were performed: one in Argentina (344 participants aged 10-15 years, 10 microg HBsAg/dose) and one in Uruguay (344 participants aged 16-45 years, 20 microg HBsAg/dose). Both vaccines were given in a 0, 1, 6 month schedule to all participants with a baseline anti-Hep B antibody titer0.6 mIU/mL. Antibody titers were measured pre-dose 1, 1 month after dose 2, pre-dose 3, and 1 month after dose 3. Statistical non-inferiority analyses were performed on seroprotection rates (SP) post-dose 3 (% with anti-Hep B titersor=10 mIU/mL; delta non-inferiority limit of -10%). In both studies, SP for the spHB vaccine was 100% and the spHB vaccine was non-inferior in terms of SP to the licensed control vaccine. GMTs post-dose 3 were approximately 1.8- and 4.1-fold higher for spHB in the 10-15 year and 16-45 year age groups, respectively. Reactogenicity was low for each vaccine, after each dose. This highly immunogenic hepatitis B candidate vaccine was selected for further investigation as a component of new pediatric combination vaccines.

Aims and background The incidental finding of nonfunctioning adrenal masses (incidentalomas) is common, but no reliable criteria in differentiating between benign and malignant adrenal masses have been defined. The aim of this preliminary study was to assess the usefulness of adrenal imaging and image-guided fine-needle aspiration cytology in patients with nonfunctioning adrenal incidentalomas with the aim of excluding or confirming malignancy before surgery. Methods Forty-two consecutive patients (18 men and 24 women; median age, 54 years; range, 25-75 years) with incidentally discovered adrenal masses of 3 cm or more in the greatest diameter were prospectively enrolled in the study. All patients underwent helical computerized tomography scan and image-guided fine-needle aspiration cytology, 33 (78.6%) underwent magnetic resonance imaging, and 26 (61.9%) underwent norcholesterol scintigraphy before adrenalectomy. Results The revised final pathology showed 30 (71.4%) benign (26 adrenocortical adenomas, of which 3 were atypical, 2 ganglioneuromas, and 2 nonfunctioning benign pheochromocytomas) and 12 (28.6%, 95% CI = 15-42) adrenal malignancies (8 adrenocortical carcinomas and 4 unsuspected adrenal metastases). The definitive diagnosis of adrenocortical carcinoma was made according to Weiss criteria and confirmed on the basis of local invasion at surgery or metastases. The sensitivity, specificity and accuracy were 75%, 67% and 83% for computerized tomography scan, 92%, 95% and 94% for magnetic resonance imaging, 89%, 94% and 92% for norcholesterol scintigraphy, and 92%, 100% and 98% for fine-needle aspiration cytology. The sensitivity and accuracy of image-guided fine-needle aspiration cytology and magnetic resonance imaging together reached 100%. Immediate periprocedural complications of fine-needle aspiration cytology occurred in 2 (4.7%) patients: self-limited pneumothorax (n = 1), and severe pain (n = 1) requiring analgesic therapy. No postprocedural or late complications were observed. Conclusions With the aim of selecting for surgery patients with a non-functioning adrenal incidentaloma of 3 cm or more in diameter, the combination of magnetic resonance imaging and fine-needle aspiration cytology should be considered the strategy of choice.

Background Given the broad age range across which the quadrivalent meningococcal conjugate vaccine MenACWY-CRM is used, coadministration with routine vaccines should be evaluated across age groups for possible immunologic interference and impact on vaccine reactogenicity and safety. Methods We summarize data from a large population of infants, adolescents and international travelers from 10 phase 3 or 4 clinical studies to evaluate coadministration of MenACWY-CRM with commonly administered vaccines. Noninferiority analyses of immune responses were performed across studies and age groups for each vaccine. Reactogenicity and safety were also assessed. Results In infants, MenACWY-CRM coadministered with routine vaccines did not reduce immune responses to diphtheria, tetanus, poliovirus, hepatitis B, Haemophilus influenzae type b, pneumococcal conjugate, measles-mumps-rubella, varicella or pertussis antigens. Noninferiority criteria were not met for some pneumococcal conjugate serotypes at 7 months of age, but no consistent trends were observed. In adolescents, coadministration did not reduce immune responses to tetanus, diphtheria and human papilloma virus vaccine antigens. Noninferiority criteria for pertussis antigens were not uniformly met in infant and adolescent studies, although the clinical relevance is unclear. In adults, coadministration did not reduce immune responses to hepatitis A/B, typhoid fever, yellow fever, Japanese encephalitis and rabies antigens. Immune responses to MenACWY-CRM were not impacted by coadministration of commonly administered vaccines. Coadministration did not increase frequencies of postvaccination adverse events in any age group. Conclusions With no clinically relevant vaccine interactions or impact on vaccine reactogenicity or safety, these results support the coadministration of MenACWY-CRM with routine vaccines in all age groups.

Neck lesions are not uncommon in children and typically present with localised swelling. The neuroradiologist's goal is the diagnosis of cervical lesions as a concomitant pathological finding, especially in cases with intraspinal spread. Neck lesions can be classified in terms of etiology as congenital, inflammatory or neoplastic, but this division is not the best suited to a radiological approach. A more useful diagnostic indicator is the location of the lesion with a further classification based on its radiological hallmarks. An assessment of age distribution is also important for a correct diagnosis.

Background. Pancreas transplantation (PTx) with portal-enteric drainage (PED) has been associated with difficulties in respect to arterial anastomosis and graft accessibility for percutaneous biopsy. We describe a new technique that circumvents these difficulties. Methods. Between April 2001 and April 2004, a total of 113 recipients were scheduled for PTx with PED. The superior mesenteric vein was approached from the right retroperitoneal aspect instead of from the anterior transmesenteric route. The pancreas graft was eventually placed in the right retroperitoneal space, being covered by the ascending colon and its mesentery. Results. One hundred ten (97.3%) PTx were performed as planned. Systemic venous effluent was preferred in three patients because of incidental diagnosis of liver cirrhosis during surgery (n= 1) and severe obesity (body mass index>35 kg/m 2 ) (n=2). The Y iliac artery graft was kept as short as possible, and arterial anastomosis was always performed with ease. After a mean follow-up period of 21.2±19.9 months, the relaparotomy rate was 13.6%. No patient died after repeat surgery, and none required multiple relaparotomies. Overall, 10 grafts were lost because of acute rejection (n=3), chronic rejection (n=2), venous thrombosis (n=2), recipient death (n=2), and late (6-month) arterial thrombosis (n=1). One-year patient and graft survival were 98.1% and 90.7%, respectively. Conclusions. Our data confirm that PTx with PED is not associated with an increased risk. The technique described has distinctive technical advantages and should be included in the repertoire of PTx.

Purpose This study was conducted to describe the various patterns of vascularity of the normal superficial lymph nodes detected using high-sensitivity power Doppler imaging according to the dimension and anatomic location of the nodes. Subjects and Methods A total of 712 lymph nodes (416 in the neck, 205 in the groin, and 91 in the axilla) were studied in 118 patients with high-sensitivity Power doppler. Three categories of vascularity were defined: absence of vascularity (type 1), hilar and perihilar vascularity (type 2), and vascularity in the entire node (type 3). The 3 types of vascularity were correlated with the anatomic location and the dimension (maximum transverse diameter) of the nodes. Results Type 3 vascularity was found in all lymph nodes with a maximum transverse diameter > 6 mm, in the 67.9% (133/196) of lymph nodes between 4 and 6 mm in diameter, and in 45.7% (42/92) of lymph nodes between 2 and 4 mm in diameter. In lymph nodes with transverse diameters of 2–6 mm, type 3 vascularity was detected in 80.7% (46/57) of the axillary nodes, in 69.0% (87/126) of the inguinal nodes, and in 40.0% (42/105) of the cervical nodes. Type 2 vascularity was seen in 14.2% (101/712) of all examined lymph nodes. The absence of vascularity (type 1) was noted in only 1.9% (8/416) of cervical and 2.0% (4/205) of inguinal nodes. Conclusions State-of-the-art power Doppler equipment can demonstrate type 3 vascularity in a high percentage of normal superficial lymph nodes. This pattern of intense, extensive—but harmonious—vascularity must be considered as an indicator of benignity. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:273–276, 2004

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal nonneoplastic hematopoietic stem cell disease characterized by an acquired mutation of the PIG-A gene with reduction or absence of CD55 and CD59. The absence of these proteins renders PNH erythrocytes susceptible to complement-mediated hemolysis. We report the case of a PNH patient before and during pregnancy until delivery. We observed and treated some postpartum thrombotic complications. Eculizumab should be used with caution in pregnancy. There are several reports supporting its use in these patients. This case should be considered paradigmatic of a series of clinical situations that may occur in the course of a pregnancy in patients with PNH: increased need for transfusion, need to increase the dose of Eculizumab, and insurgence of fetal sufferance. Moreover, after delivery, the patient, despite adequate prophylaxis with low-molecular-weight heparins, presented severe complications: development of pleural and peritoneal effusion, pulmonary embolism, bilateral upper limbs thrombophlebitis, and a possible abdominal angina with a transient paralytic ileus. All these complications were overcome and now the baby is healthy and the mother has returned to the usual therapeutic regimen.

Aim of the work was the experimental validation of musculoskeletal models of lower limbs during isokinetic knee flexion-extensions at different angular speeds, using OpenSim® and AnyBody® codes. The adopted approach was: (i) to record the kinematic, kinetic and EMG data on two healthy subjects, (ii) to implement the scaled numerical models of the two subjects within the two codes, (iii) to simulate the isokinetic motions of each subject in each code and (iv) to compare the numerical and experimental activation results in terms of peak, phase and area errors. Results showed a good agreement for extensor muscles, giving an encouraging confirmation about the possibility of using such codes for the evaluation of joint loads.

Objective Inverted papilloma (Schneiderian-type papilloma), involving the middle ear and mastoid as a primary lesion or as an extension of a sinonasal papilloma, is an extremely rare occurrence. Study design The study design was a case report format with a review of the literature. Epidemiologic, diagnostic, therapeutic and follow-up problems are discussed. Setting Academic, tertiary referral hospital. Patient and methods The patient underwent Wullstein type I tympanoplasty and complete mastoidectomy, revealing obliteration of the pneumatic cells by polypoid tissue. The middle ear was completely filled by polypoid tissue. Histopathologic examination revealed an inverted papilloma of the middle ear and mastoid. Conclusion Literature reports indicate that inverted papillomas of the middle ear and mastoid differ pathogenically and epidemiologically from sinonasal inverted papillomas. Recurrence rates and association with squamous cell carcinoma are higher in Schneiderian-type papillomas of the middle ear than in inverted papillomas of the nose and paranasal sinuses. Long-term follow-up after removal of inverted papilloma of the middle ear and mastoid is mandatory. Magnetic resonance imaging is the first follow-up examination to perform.

Image-guided, fine-needle aspiration (FNA) cytology is performed currently in patients with malignant disease who have suspected adrenal metastases. The objective of this study was to evaluate the usefulness and safety of FNA cytology in patients with incidental adrenal masses and functioning tumors.Computed tomography (CT)-guided or ultrasound-guided aspirates using 21-23-gauge needles were performed successfully in 70 patients with functioning (n = 38 patients) and nonfunctioning (n = 32 patients) adrenal masses (median size, 4 cm; range, 3-12 cm) that were detected previously by CT scans.Definitive histology was available in 68 patients (97.1%), showing 53 benign tumors (77.9%), 11 primitive malignant tumors (16.2%), and 4 unsuspected adrenal metastases (5.9%) in patients with unknown primary tumors. In two patients with aspirate reports that ruled out malignancy, the mass was unchanged on CT scan follow-up; thus, they were considered benign lesions. The benign masses were significantly smaller (P0.01), although seven malignant tumors (46.7%) measured 3-4 cm in greatest dimension, and eight benign lesions (14.5%) measured 5-6 cm in greatest dimension. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 96.4%, 83.3%, 91.4%, and 90.0%, respectively, for CT scan and 93.3%, 100%, 100%, 98.2%, and 98.6%, respectively, for FNA cytology. The morbidity rate of image-guided FNA cytology was 4.3% (two patients with self-limited, asymptomatic pneumothorax and one patient with spontaneously resolved adrenal hematoma).Adrenal FNA cytology represents a safe and specific procedure for evaluating patients with adrenal masses measuring2 cm in greatest dimension. FNA is able to reveal malignancies and unsuspected pheochromocytomas and should be performed in all patients with adrenal tumors whenever requested for surgical planning.

The aim of this study was to discuss the role of preoperative ultrasound (US) scanning and sentinel node biopsy (SNB) in melanoma patients. 100 patients underwent SNB following preoperative US scan and lymphoscintigraphy; patent blue dye (PBD) was injected before biopsy. Intra-operative lymphoscintigraphy (IL) was performed in 51 basins. All nodes were examined with histology and immunohistochemistry. Sensitivity and specificity of US scanning was 33% and 100%, respectively; 7% were true positives. The low sensitivity was mainly due to the resolution power of the US scanner (2 mm) which was unable to identify all the patients with microdeposits. PBD associated with IL identified SNs in all cases. In all patients with Breslow >1.5 mm and in all cases with two metastatic SNs, further positive additional nodes were found. The mean counts per 10 s (CP10S) ratio for SN and non-SN values was 5.62 (1.29–23.51) and 3.09 (1.03–10.99) in the intra-operative and extra-operative phases, respectively. US scanning and preoperative lymphoscintigraphy associated with PBD allows preoperative patient selection and accurate SN(s) identification. Breslow thickness and the number of metastatic SN(s), but not their type, are correlated with disease spread; CP10S contributed to the differentiation amongst the nodes and the determining of procedure's completion.

Active surveillance of ambulatory and hospitalized children 2-23 months old in Cordoba, Argentina for invasive pneumococcal disease and radiographically confirmed "obvious" pneumonia revealed annual incidences of 206.8 and 2422 cases, respectively, per 100,000 children. The invasive pneumococcal disease incidence was substantially higher than those previously reported from Latin America and Europe.

Prenatal diagnosis of cloacal exstrophy can be challenging during pregnancy and, subsequently, the counseling very difficult. Available ultrasonographic criteria may be inadequate, especially in early gestational ages. A case of early prenatal detection of cloacal exstrophy with fetal magnetic resonance imaging is reported herein for the first time.

International audience; Ecologically-appropriate management of natural and constructed surface water bodies has become increasingly important given the growing anthropogenic pressures, statutory regulations, and climate-change impacts on environmental quality. The development of management strategies requires that a number of knowledge gaps be addressed through interdisciplinary research efforts particularly focusing on the water-biota and water-sediment interfaces where most critical biophysical processes occur. This paper discusses the current state of affairs in this field and highlights potential paths to resolve critical issues, such as hydrodynamically-driven mass transport processes at interfaces and associated responses of organisms through the development of traits. The roles of experimental methods, theoretical modelling, statistical tools, and conceptual upscaling methods in future research are discussed from both engineering and ecological perspectives. The aim is to attract the attention of experienced and emerging hydraulic and environmental researchers to this research area, which is likely to bring new and exciting discoveries at the discipline borders.

In a double-blind randomized controlled trial, Xavier Saez-Llorens and colleagues examine the vaccine efficacy of PHiD-CV against community-acquired pneumonia in young children in Panama, Argentina, and Columbia. Please see later in the article for the Editors' Summary, Background The relationship between pneumococcal conjugate vaccine–induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed. Methods and Findings This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15–18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization–defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28–30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140) and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: −1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95% CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%) against any IPD. Results were consistent between intent-to-treat and per-protocol analyses. Serious adverse events were reported for 21.5% (95% CI: 20.7%, 22.2%) and 22.6% (95% CI: 21.9%, 23.4%) of PHiD-CV and control recipients, respectively. There were 19 deaths (n = 11,798; 0.16%) in the PHiD-CV group and 26 deaths (n = 11,799; 0.22%) in the control group. A significant study limitation was the lower than expected number of captured AOM cases. Conclusions Efficacy was demonstrated against a broad range of pneumococcal diseases commonly encountered in young children in clinical practice. Trial registration www.ClinicalTrials.gov NCT00466947 Please see later in the article for the Editors' Summary, Editors' Summary Background Pneumococcal diseases are illnesses caused by Streptococcus pneumoniae bacteria, pathogens (disease-causing organisms) that are transmitted through contact with infected respiratory secretions. S. pneumoniae causes mucosal diseases–infections of the lining of the body cavities that are connected to the outside world–such as community-acquired pneumonia (CAP; lung infection) and acute otitis media (AOM; middle-ear infection). It also causes invasive pneumococcal diseases (IPDs) such as septicemia and meningitis (infections of the bloodstream and the covering of the brain, respectively). Although pneumococcal diseases can sometimes be treated with antibiotics, CAP and IPDs are leading global causes of childhood deaths, particularly in developing countries. It is best therefore to avoid S. pneumoniae infections through vaccination. Vaccination primes the immune system to recognize and attack pathogens rapidly and effectively by exposing it to weakened or dead pathogens or to pathogen molecules that it recognizes as foreign (antigens). Because there are more than 90 S. pneumoniae variants (“serotypes”), each characterized by a different antigenic polysaccharide (complex sugar) coat, S. pneumoniae vaccines have to include antigens from multiple serotypes. For example, the PHiD-CV vaccine contains polysaccharides from ten S. pneumoniae serotypes. Why Was This Study Done? Although in most countries PHiD-CV has been licensed for protection against IPD and pneumococcal AOM, at the time of study, it was not known how well it protected against CAP and overall AOM, which are important public health problems. In this double-blind randomized controlled trial (the Clinical Otitis Media and Pneumonia Study; COMPAS), the researchers investigate the efficacy of PHiD-CV against CAP and AOM and assess other clinical end points, such as IPD, in Latin American infants. Double-blind randomized controlled trials compare the effects of interventions by assigning study participants to different interventions randomly and measuring predefined outcomes without the study participants or researchers knowing who has received which intervention until the trial is completed. Vaccine efficacy is the reduction in the incidence of a disease (the number of new cases that occur in a population in a given time) among trial participants who receive the vaccine compared to the incidence among participants who do not receive the vaccine. What Did the Researchers Do and Find? The researchers enrolled around 24,000 infants living in urban areas of Argentina, Panama, and Colombia. Half the infants were given PHiD-CV at 2, 4, and 6 months of age and a booster dose at age 15–18 months. The remaining infants were given a hepatitis control vaccine at the same intervals. The trial's primary end point was likely bacterial CAP (B-CAP) –radiologically confirmed CAP, with the airspaces (alveoli) in the lungs filled with liquid instead of gas (alveolar consolidation) or with non-alveolar infiltrates and raised blood levels of C-reactive protein (a marker of inflammation). In a planned interim analysis, which was undertaken after an average follow-up of 23 months, the vaccine efficacy in the per-protocol cohort (the group of participants who actually received their assigned intervention) was 22% against B-CAP. Intent-to-treat vaccine efficacy in the interim analysis (which considered all the trial participants regardless of whether they received their assigned intervention) was 18.2%. At the end of the study (average follow up 30 months), the vaccine efficacy against B-CAP was 18.2% and 16.7% in the per-protocol and intent-to-treat cohorts, respectively. Per-protocol vaccine efficacies against clinically confirmed AOM and vaccine serotype AOM were 16.1% and 67.1%, respectively. Against any IPD and against vaccine serotype IPD, the respective vaccine efficacies were 65% and 100%. Finally, about one-fifth of children who received PHiD-CV and a similar proportion who received the control vaccine experienced a serious adverse event (for example, gastroenteritis); 19 children who received PHiD-CV died compared to 26 children who received the control vaccine. What Do These Findings Mean? These findings indicate that in Latin America, a region with an intermediate burden of pneumococcal disease, PHiD-CV is efficacious against a broad range of pneumococcal diseases that often affect young children. The accuracy of these findings may be limited by the withdrawal of 14% of participants from the trial because of adverse media coverage and by the low number of reported cases of AOM. Moreover, because most study participants lived in urban areas, these findings may not be generalizable to rural settings. Despite these and other study limitations, these findings provide new information about the magnitude of the effect of PHiD-CV vaccination against CAP and AOM, two mucosal pneumococcal diseases of global public health importance. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001657. The US Centers for Disease Control and Prevention provides information for patients and health professionals on all aspects of pneumococcal disease and pneumococcal vaccination, including personal stories Public Health England provides information on pneumococcal disease and on pneumococcal vaccines The not-for-profit Immunization Action Coalition has information on pneumococcal disease, including personal stories The GAVI Alliance provides information about pneumococcal disease and the importance of vaccination MedlinePlus has links to further information about pneumococcal infections, including pneumonia and otitis media (in English and Spanish) More information about COMPAS is available The European Medicines Agency provides information about PHiD-CV (Synflorix)

The aim of this study was to ascertain the utility of contrast-enhanced ultrasound in assessing the significance of focal cortical thickening in the lymph nodes of patients followed up after surgery for cutaneous melanoma.Ultrasound was used to examine 460 consecutive patients to identify nodes with focal hypoechoic cortical thickening. Patients whose nodes revealed these features underwent contrast-enhanced ultrasound and ultrasound-guided fine-needle aspiration cytology (FNAC) focusing on the area of cortical thickening. Enhancement in the arterial and parenchymal phases was evaluated: A generalized homogeneous or intense enhancement was considered benign and the presence of a perfusion defect was considered metastatic.After exclusion of 24 patients with frank signs of malignancy at gray-scale ultrasound, the study included 436 patients. Focal hypoechoic cortical thickening was seen in 44 of 436 nodes in as many patients. In 29 nodes, the area of focal thickening showed contrast enhancement similar to that of the remaining cortex on contrast-enhanced ultrasound. In 15 nodes, the area of cortical thickening was less well vascularized than the adjacent parenchyma in the arterial phase and there were areas with perfusion defects that were more evident in the parenchymal phase. FNAC focusing on the areas of focal cortical thickening identified 13 metastatic nodes and 31 nodes with benign features. Contrast-enhanced ultrasound compared with FNAC correctly classified 42 of 44 nodes, showing a sensitivity of 100% and a specificity of 99.5%.Although our findings need to be confirmed in larger series, they indicate that contrast-enhanced ultrasound can be useful in clinical practice for characterizing focal cortical thickening in lymph nodes. The exclusion or identification of regional lymph node metastases is of fundamental importance in oncologic staging because this issue directly influences both the prognosis and the choice of therapeutic strategy.

The efficacy of a rotavirus vaccine against severe rotavirus gastroenteritis when coadministered with routine Expanded Program on Immunization (EPI) vaccines including oral polio vaccine (OPV) was evaluated in this study.Double-blind, randomized (2:1), placebo-controlled study conducted across 6 Latin American countries. Healthy infants (N = 6568) 6 to 12 weeks of age received 2 doses of RIX4414 vaccine or placebo following a 0, 1- to 2-month schedule. Routine vaccines including OPV were coadministered according to local EPI schedule. Vaccine efficacy (VE) against severe rotavirus gastroenteritis caused by circulating wild-type rotavirus from 2 weeks post-Dose 2 until 1 year of age was calculated with 95% confidence interval [CI]. Safety was assessed during the entire study period. Immunogenicity of RIX4414 and OPV was also assessed.During the efficacy follow-up period (mean duration = 7.4 months), 7 and 19 cases of severe rotavirus gastroenteritis were reported in the vaccine and placebo groups, respectively, with a VE of 81.6% (95% CI: 54.4-93.5). VE against severe rotavirus gastroenteritis caused by G1 type was 100% (95% CI:0-100) and 80.6% (95% CI: 51.4-93.2) against the pooled non-G1 rotavirus types, respectively. There was no difference (P = 0.514) in the incidence of serious adverse events reported in the 2 groups. Antirotavirus IgA seropositivity rate at 1 to 2 months post-Dose 2 was 61.4% (95% CI: 53.7-68.6) in the RIX4414 group; similar seroprotection rates (≥96.0%) against the 3 antipoliovirus types was observed 1 month post-Dose 3 of OPV in both groups.RIX4414 was highly efficacious against severe rotavirus gastroenteritis caused by the circulating wild-type rotavirus (G1 and non-G1) when coadministered with routine EPI vaccines including OPV.

Background and aims Assessment of a new, fully liquid, investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim, Sanofi Pasteur), containing the same active ingredients as Pentaxim (DTaP-IPV//PRT-T) and 10 μg Hansenula polymorpha-derived recombinant hepatitis B (Hep B) surface antigen, Sanofi Pasteur, in Argentinean infants. Methods Infants born to Hep B surface antigen seronegative mothers were randomized to receive the DTaP-IPV-Hep B-PRP-T vaccine or Pentaxim and Engerix B Pediatrico (Hep B monovalent) vaccines at 2, 4, 6 months of age. Antibody titers were measured before and 1 month after 3-month primary vaccination. Noninferiority analyses were performed on seroprotection/seroconversion rates. Safety was evaluated descriptively up to 1 month after primary vaccination. Results A total of 624 participants were enrolled, 312 participants were randomized to each group, and 604 participants completed the trial. The DTaP-IPV-Hep B-PRP-T vaccine was demonstrated as noninferior to the Pentaxim and Hep B monovalent vaccines with seroprotection/seroconversion rates 1 month postdose 3 for each valence. The anti-Hep B geometric mean titer 1-month postdose 3 for the investigational DTaP-IPV-Hep B-PRP-T primary series was similar to the monovalent Hep B control. The overall incidence of adverse events was similar among the 2 groups. Conclusions The new, fully liquid, investigational DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) is highly immunogenic and safe when compared with licensed comparators, warranting further development.

Background Diphtheria-tetanus-whole-cell pertussis (DTPw)-based combination vaccines are an attractive option to rapidly achieve high coverage and protection against other important pathogens, such as hepatitis B virus (HBV) and Haemophilus influenzae type B (Hib). To ensure adequate antigen supply, GlaxoSmithKline Biologicals has introduced a new DTPw antigen source and developed a new DTPw-HBV/Hib combination vaccine containing a reduced amount of Hib polyribosylribitol phosphate (PRP). This study was undertaken to compare the immunogenicity and reactogenicity of this new DTPw-HBV/Hib vaccine with a licensed DTPw-HBV/Hib vaccine (Tritanrix™-HBV/Hib). Methods This was a randomized, partially-blind, multicenter study in three countries in Latin America (Argentina, Chile and Nicaragua). Healthy children received either the new DTPw-HBV/Hib vaccine (1 of 3 lots; n = 439; double-blind) or Tritanrix™-HBV/Hib (n = 146; single-blind) co-administered with oral poliovirus vaccine (OPV) at 2, 4 and 6 months, with a booster dose at 18-24 months. Results One month after the end of the 3-dose primary vaccination course, the new DTPw-HBV/Hib vaccine was non-inferior to Tritanrix™-HBV/Hib in terms of seroprotection/vaccine response rates for all component antigens; ≥97.3% and ≥93.9% of subjects in the two groups, respectively, had seroprotective levels of antibodies against diphtheria, tetanus, hepatitis B and Hib and a vaccine response to the pertussis component. Persistence of antibodies against all vaccine antigens was comparable between groups, with marked increases in all antibody concentrations after booster administration in both groups. Both vaccines were generally well-tolerated as primary and booster doses. Conclusions Results confirm the suitability of this new DTPw-HBV/Hib vaccine comprising antigens from a new source and a reduced PRP content for inclusion into routine childhood vaccination programs. Trial registration http://www.clinicaltrials.gov NCT00332566

BACKGROUND: It is debated whether patients with melanoma who undergo lymphadenectomy after a positive sentinel lymph node (SN) biopsy (SNB) have a better prognosis compared with patients who are treated for clinically evident disease. METHODS: The records of 190 patients with cutaneous melanoma who underwent radical lymph node dissection after a positive SNB (completion lymph node dissection [CLND]; n = 100) or who had clinically evident lymph node metastasis (therapeutic lymph node dissection [TLND]; n = 90) were analyzed. Moreover, the MEDLINE, EMBASE, and Cochrane databases were searched for studies that investigated the survival impact of SNB-guided CLND compared with TLND for clinically evident disease. Standard meta-analysis methods were used to calculate the overall treatment effect across eligible studies. RESULTS: In the authors' series, tumor characteristics did not differ significantly between patients who underwent CLND and those who underwent TLND. After a median follow-up of 52.6 months, the 5-year overall survival rate did not differ significantly between CLND patients and TLND patients (68.9% vs 50.4%, respectively; log-rank test; P = .17). In contrast, a meta-analysis of 6 studies (n = 2633) that addressed this issue (including the authors' own series) indicated that there was a significantly higher risk of death for patients who underwent TLND compared with that for patients who underwent CLND (hazard ratio, 1.60; 95% confidence interval, 1.28-2.00; P < .0001). CONCLUSIONS: Although no significant survival difference was observed in either series, the pooling of summary data from all the studies that dealt with this issue suggested that SNB-guided CLND is associated with a significantly better outcome compared with TLND for clinically evident lymph node disease. Cancer 2010. © 2010 American Cancer Society.

To investigate the influence of a branched-chain amino acid (BCAA) supplementation on chronic hypoxia-related loss of body mass and muscle loss, 16 subjects [age 35.8 (SD 5.6) years] participating in a 21-day trek at a mean altitude of 3,255 (SD 458) m, were divided in two age-, sex- and fitness-matched groups and took either a dietary supplementation of BCAA (5.76, 2.88 and 2.88 g per day of leucine, isoleucine and valine, respectively) or a placebo (PLAC) in a controlled double-blind manner. Daily energy intake at altitude decreased by 4% in both groups compared with sea level. After altitude exposure both groups showed a significant loss of body mass, 1.7% and 2.8% for BCAA and PLAC, respectively. Fat mass had decreased significantly by 11.7% for BCAA and 10.3% for PLAC, whereas BCAA showed a significantly increased lean mass of 1.5%, as opposed to no change in PLAC. Arm muscle cross-sectional area tended to increase in BCAA, whereas there was a significant decrease of 6.8% in PLAC (P < 0.05 between groups). The same tendency, although not significant, was observed for the thigh muscle cross-sectional area. On the whole it seemed that PLAC had been catabolizing whereas BCAA had been synthesizing muscle tissue. Single jump height from a squatted position showed a similar tendency to increase in both groups. Lower limb maximal power decreased less in BCAA than in PLAC (2.4% vs 7.8%, P < 0.05). We concluded that BCAA supplementation may prevent muscle loss during chronic hypobaric hypoxia.

In recent decades, with the widespread diffusion of the supracricoid laryngectomy in the treatment of selected advanced laryngeal neoplasm, the indications to non-conservative surgery are less frequent than in past. We report the case of a patient in whom a planned supracricoid laryngectomy was intraoperatively converted in an extended partial laryngectomy with tracheohyoidoepiglottopexy for a tumor involving the cricoid cartilage.

We investigated the efficacy and safety of 1 versus 2 doses of live attenuated influenza vaccine (LAIV) in influenza vaccine-naive children aged 6 to36 months.Subjects were randomized to 1 of 4 regimens in year 1: 2 doses LAIV, 1 dose LAIV, excipient placebo, or saline placebo. In year 2, LAIV recipients were to receive 1 dose of LAIV and placebo recipients were to receive saline placebo. Because of an unintended treatment allocation error in year 2, 1 block of subjects who were randomized to LAIV received saline placebo and 1 block who were randomized to placebo received LAIV.In year 1, vaccine efficacy versus placebo among recipients of 2 and 1 doses of LAIV was 73.5% and 57.7%, respectively, against antigenically similar strains. In year 2, absolute efficacy of a single dose of LAIV was 73.6% and 65.2%, respectively, in recipients of 2 and 1 doses of LAIV in year 1. Year 2 efficacy was 57.0% in subjects who received 2 doses of LAIV in year 1 and placebo in year 2. Safety and tolerability of LAIV were consistent with previous studies. Reactogenicity was similar between placebo groups. Seroconversion rates were significantly higher in the 2-dose versus the 1-dose LAIV group in year 1 and in both LAIV groups versus placebo in years 1 and 2.One dose of LAIV provided clinically significant protection against influenza in young children previously unvaccinated against influenza; 2 doses provided additional protection. Protection after 2 doses in year 1 persisted through a second season without revaccination. LAIV excipients were not a major contributor to reactogenicity. These benefits provide support for increased use of LAIV in childrenor =2 years of age.

Sonoelastography is an imaging technique that provides information on tissue elasticity. Its use as a diagnostic procedure is based on the premise that pathological processes like cancer alter the physical characteristics of the involved tissue. Ultrasonographic studies of the neck can reveal the nonpalpable thyroid nodules, but the nature of these lesions generally has to be established on the basis of FNAB findings. In our hands, sonoelastography displayed a diagnostic accuracy of 86.2% in identifying thyroid nodule malignancy, with positive and negative predictive values (PPV and NPV) of 64% and 94.5%, respectively. In the study of cervical lymph nodes, the results were less impressive (sensitivity 75%, specificity 80%, accuracy 77%, PPV 80%, NPV 70%), but the information obtained with this technique can in our opinion be a useful adjunct to sonographic findings. Indeed, in 5 lymph nodes with sonographic features consistent with malignancy, sonoelastography revealed diffuse elasticity that was indicative of benign disease, which was confirmed by pathological studies. Other nodular lesions of the neck can also be evaluated with sonoelastography, including enlarged parotid glands, but the data in the literature are too limited to allow hypotheses on the role of this imaging modality in this field. Sonoelastography is rapid and simple to perform, and it appears to be a potentially useful tool for the differential diagnosis of neck nodules. This is particularly true of thyroid nodules. Our experience with these lesions indicates that diffuse elasticity is strongly correlated with benign disease. If this finding is confirmed in larger studies, sonoelastography might be used to identify thyroid nodules that do not require immediate biopsy.SommarioL'elastosonografia è una tecnica di imaging che fornisce informazioni relative alla elasticità dei tessuti e che può essere utilizzata nella pratica clinica basandosi sul presupposto che i processi patologici, come il cancro, inducono modificazioni della caratteristiche fisiche dei tessuti ammalati.Lo studio ecografico della loggia cervicale permette di individuare formazioni nodulari non palpabili all'interno della tiroide, tuttavia l'accuratezza diagnostica di questa tecnica è scarsa e per tale motivo il ricorso alla FNAB è spesso necessario.Nella nostra esperienza l'elastosonografia ha dimostrato, nella diagnosi differenziale dei nodi tiroidei, un'accuratezza diagnostica del 86,2% con VPN 94,5% e VPP 64%.Nello studio dei linfonodi cervicali i risultati ottenuti sono meno brillanti (sensibilità, specificità e accuratezza rispettivamente del 75%, 80% e 77% con VPP e VPN di 80% e 70%), ma riteniamo che le informazioni ottenibili possono in molti casi essere utili per integrare i dati ecografici; in particolare in 5 casi di linfonodi con caratteristiche morfo-strutturali indicative di malignità, l'elastosonografia ha dimostrato un pattern di completa elasticità, riconoscendo la natura benigna confermata dalle successive indagini.Altre formazioni nodulari del collo possono essere valutate con elastosonografia, in particolare le tumefazioni parotidee, ma non esistono ancora in letteratura esperienze sufficientemente ampie da indicare l'eventuale contributo clinico in questo campo.L'elastosonografia è una tecnica rapida e di facile esecuzione che sembra fornire un interessante contributo nella differenziazione tra formazioni nodulari del collo.In particolare si è osservata una stretta correlazione tra noduli tiroidei totalmente elastici e quadro di benignità; se tale rapporto venisse confermato in una casistica più ampia permetterebbe di escludere in questi casi l'immediato ricorso alla FNAB.

Purpose Ultrasound of the neck detects a large number of non-palpable thyroid nodules in the population, but it offers poor diagnostic accuracy (the presence of microcalcifications is the only statistically significant criterion indicative of malignancy). The aim of this study is to evaluate elastography, a technique which allows differentiation between pathological and normal tissue by determining its hardness and which could also prove useful in the characterisation of thyroid nodules. Materials and methods In this prospective study, 51 thyroid nodules in 40 consecutive patients were examined (25 women, 15 men, mean age +/- SD, 54 +/- 13.4). Elastosonography was performed by real-time, free-hand technique, using Logos HiVision equipment with a 10 MHz transducer and lesions were classified and scored in 4 classes of hardness. All patients were also examined by grey scale high frequency ultrasound and colour Doppler. Final diagnoses were obtained from cytological and/or histological evaluation. Results Final diagnoses revealed 11 malignant and 40 benign nodules. Only in two cases ultrasound demonstrated signs useful for a differential diagnosis (intrinsic microcalcifications). Correct differentiation of malignant from benign nodules was obtained by elastosonography in 43 / 51 cases with 5 false positives (FP) and 3 false negatives (FN). Specificity, sensitivity and accuracy were 87.5 %, 81.8 % and 86.2 %, respectively. Predictive negative value (PNV) and predictive positive value (PPV) were 94.5 % and 64 % area under the curve (AUC) 0.86. Conclusion Elastosonography provides an interesting contribution to the differentiation of malignant and benign thyroid nodules. Particularly worthy of mention is that an entirely elastic nodule pattern was observed only in relation to benign nodules, a result which would suggest that immediate recourse to FNAB might be avoided.

The evaluation of potential living kidney donors requires an accurate study of renal function and morphology. The gold standard to assess renal function is the measurement of glomerular filtration rate (GFR). However, GFR is often estimated from serum creatinine (SCr), cystatin C (SCys), or creatinine clearance (CCr). Otherwise, GFR is predicted using formulas based on SCr or SCys. Ultrasound scanning evaluates morphology and dimensions, while scintigraphy provides information on morphofunctional symmetry of kidneys. The aim of this study in 79 potential donors was to assess the accuracy of the tests employed to estimate GFR and the utility of renal ultrasound and scintigraphy for morphofunctional evaluation of potential donors. GFR (clearance of 99m Tc-DTPA) was compared with estimates obtained with Cockcroft and Gault (CG-CCr) and Modification of Diet in Renal Disease (MDRD-GFR) formulas, and from SCys (Cys-GFR). The correlation with GFR was statistically significant for SCys and for all estimates, but not for SCr. CCr showed a poor agreement with GFR, with a large range of agreement and a marked and significant overestimation of GFR (33.8 mL/min). The accuracy of CG-CCr and MDRD-GFR as indicators of a GFR < 80 mL/min was better than that of Cys-GFR and CCr. However, their mean prediction errors versus GFR were relevant. Renal dimensions, particularly renal volume, showed a good correlation with GFR. The correlation was higher than that of all prediction equations. The direct measurement of GFR remains the reference method to assess renal function in potential kidney donors. The measurement of renal dimensions can provide useful information also on renal function.

A case of meconium periorchitis detected by fetal MRI and misdiagnosed during pregnancy as inguinoscrotal hernia is reported for the first time. A full-term black boy presented at birth with an asymptomatic, ‘stony-hard’, scrotal mass suggestive of an in utero testicular torsion or testicular/paratesticular tumor. Early surgical treatment resulted in the removal of paratesticular yellowish amorphous material. Histology was consistent with the diagnosis of meconium periorchitis, a rare and benign condition resulting from healed intrauterine bowel perforation.

Objectives Recently, jawbone osteonecrosis has been reported as a potential adverse effect of bisphosphonates administration. This paper considers and highlights histopathologic and radiologic features of this condition. Study design Eleven patients, owing to unresponsiveness to conservative treatment and uncontrollable pain, underwent surgical resection of diseased jawbone after extensive hyperbaric oxygen therapy. A thorough clinical, laboratory, and imaging study was performed. Surgical specimens underwent histopathologic and immunohistochemical evaluation. Results Computerized tomography (CT) scans showed increased bone density, periosteal reaction, and bone sequestration in advanced stages. With magnetic resonance imaging (MRI), exposed areas showed a low signal in T1- and T2-weighted and inversion recovery images, which suggests low water content and is histopathologically correlated with paucity in cells and vessels (osteonecrotic pattern). Unexposed diseased bone was characterized by T1 hypointensity and T2 and IR hyperintensity, which suggests high water content and inflammation, associated with hypercellularity, osteogenesis, and hypervascularity (osteomyelitic pattern). Conclusions Diseased bone extends beyond the limits of the bone exposed in the oral cavity. Histopathologic examination correlated well with CT and MRI, which are the choice for the evaluation of bisphosphonate-associated jawbone osteonecrosis.

The aim of this study was to assess the performance of experimental software (Qontraxt) intended to provide automated quantification of sonographic signal intensity, which is related to the contrast enhancement of lymph node tissue, to differentiate benign from malignant lymph nodes.In 31 patients (age range, 24-86 years; mean age +/- SD, 53.6 +/- 14.4 years) a single lymph node per patient was evaluated on sonography after the administration of sulfur hexafluoride-filled microbubbles. The stored sonographic images were analyzed and processed into chromatic maps that had numeric values related to the amount of contrast. The lymph node regions in which the increase of signal intensity values with respect to baseline were highest (maximum signal intensity value [SImax]) and lowest (minimum signal intensity value [SImin]) were identified, and the corresponding numeric data were stored. Statistical analyses were performed by means of the Student's t test; a p value of less than 0.05 was considered to be statistically significant.Histopathologic analysis revealed metastatic lesions in 12 of the 31 lymph nodes; the remaining 19 were benign (16 reactive lymph nodes, two cases of granulomatous lymphadenitis, and one case of tubercular lymphadenitis). Values obtained from the SImax regions showed no consistent difference between benign and malignant lymph nodes; on the other hand, values from the SImin regions comparing baseline and maximal contrast-enhanced values were significantly different in the two groups (p0.001). Confidence for characterization of malignancy was significant using the difference between values from SImax and SImin regions, with the higher diagnostic value from 24 to 31 inclusive: sensitivity, 92% (11/12); specificity, 89% (17/19); positive predictive value, 85% (11/13); and accuracy, 90% (28/31).The software being tested proved to be useful in differentiating benign from metastatic lymph nodes on the basis of the quantitative data it provided.

The gold standard to assess renal function is the measurement of glomerular filtration rate (GFR). For practical reasons, renal function is often evaluated from serum creatinine (S Cr) or cystatin C (S Cys), and GFR is predicted from SCr. Ultrasound scanning of the kidneys is used only to evaluate renal morphology. The aim of this study was to evaluate the relationship between sonographic renal dimensions and GFR in renal transplant recipients and in kidney donors. GFR (urinary clearance of (99m)Tc-DTPA), S Cr, and S Cys were measured in 33 donors (28 females [F], 5 males [M]; SCr, 0.81-1.90 mg/dL) and 30 recipients (8 F, 22 M; SCr, 0.96-2.42 mg/dL). GFR was also predicted using the Cockcroft and Gault (CG) formula and with the simplified Modification of Diet in Renal Disease (MDRD) formula. Length, width, and depth of kidneys and renal sinus were measured using renal sonography. Among sonographic measurements, kidney length showed the best correlation with GFR. A closer correlation with GFR was found in donors (r = 0.639; P < .00007) than in recipients (r = 0.511; P < .005). In either case, the correlation of kidney length with GFR was greater than that of S Cr or S Cys, and similar to that of CG or MDRD GFR. Accuracy of kidney length as an indicator of GFR impairment was not statistically different from laboratory tests. Only in donors did CG show better accuracy. In conclusion, renal dimensions at sonography closely correlated with GFR. Thus, renal sonography can give information also on the function of the renal graft and of the remaining kidney of living donors.

Purpose Because angiomyolipoma is less common in children than in adults, its diagnosis can be difficult. We present 3 cases of pediatric angiomyolipoma in which diagnostic problems resulted due to the presenting characteristics. Materials and Methods We report on 3 children with unilateral renal angiomyolipoma. Computerized tomography (CT) and ultrasonography revealed 3 large renal masses, 20, 7 and 8 cm. in diameter, respectively. A correct diagnosis was not made preoperatively in any case by CT, ultrasound or fine needle biopsy. Wilms tumor was suspected in the first patient who received preoperative chemotherapy. Imaging was inconclusive in the other 2 cases. Results All patients underwent surgical exploration and subsequent nephrectomy due to the large size of the tumor. At followup 33, 23 and 13 months postoperatively all children were well without signs of recurrence. Conclusions It has been reported that the demonstration of fat on renal ultrasound and CT can diagnose angiomyolipoma in 95% of the cases. Most radiologists rely solely on CT demonstration of lipid density in the renal mass to diagnose angiomyolipoma but the identification at imaging of lipid tissue may be difficult in small tumors. In our cases the fat content of the tumors was less than 10% despite the large size. This low fat content results in misdiagnosis, since fatty tissue is also present in other renal tumors, such as lipoma, liposarcoma, teratoma and Wilms tumors. We recommend conservative surgery when tumor size permits in pediatric patients with angiomyolipoma to avoid chemotherapy.

The aim of this study was to evaluate the sensitivity, specificity and accuracy of axillary ultrasonography (US) and (99m)Tc-sestamibi scintimammography (SSM) in patients with breast cancer (BC) undergoing curative surgery.A series of 77 consecutive women (median age 54 years, range 36-70) with primary BC underwent both US and SSM from 2 to 15 (median 4) days prior to curative surgery. The results of imaging studies were compared against the final pathology. Breast-conserving surgery with axillary node (AN) dissection was performed in 49 (63.6%) patients, and modified radical mastectomy in 28 (36.4%) patients, according to the tumour staging.Final pathology showed 5 pT1bN0, 1 pT1bN1, 28 pT1cN0, 19 pT1cN1, 7 pT2N0, and 17 pT2N1 BC. Overall, 719 AN were removed of which 106 (14.7%) were metastatized nodes (median 3, range 1-5 per patient). The sensitivity, specificity and accuracy were 67.6%, 80.0%, and 74.0% for US, 78.4%, 85.0%, and 81.8% for SSM, and 91.9%, 92.5%, and 92.2% for US and SSM together, respectively. There was a significant difference (p0.05) in the number of metastatized AN between patients with metastases correctly detected and undetected by both US (3.1+/-1.3 vs. 2.0+/-0.7) and SSM (3.2+/-1.3 vs. 1.7+/-0.7).Although the results of each diagnostic tests are strictly dependent on the number of the metastatized AN, the combination of axillary US and SSM is a sensitive low-cost procedure that should be suggested in all patients with BC, when a preoperative evaluation of the AN status is required.

The preferential use of tacrolimus (Prograf) over cyclosporine microemulsion (Neoral) in simultaneous pancreas-kidney transplantation (SPKTx) is mainly based on historical, retrospective studies. We herein report the 3-year results of a single-center, prospective, randomized comparison of the two calcineurin inhibitors in the setting of mycophenolate mofetil (MMF)-based immunosuppression and portal drainage of pancreas allografts.Between May 2001 and August 2004, 47 SPKTx recipients who were stratified by recipient sex, were alternatively assigned to treatment with Neoral (n = 22) or Prograf (n = 25). Concurrent immunosuppression included induction treatment with basiliximab and maintenance with MMF and steroids.After a median follow-up of 24.0 months, all patients remained in the study arm into which they were initially enrolled. No pancreas rejection episode was observed. One acute kidney rejection was recorded in the Neoral arm (4.5%) as compared with 7 (28.0%) including one steroid-resistant episode, in the Prograf arm (P = .03). The cumulative incidence of adverse events was 31.8% (n = 7) in the Neoral arm compared with 92.0% (n = 23) in the Prograf arm (P.0001). One patient died in each study arm. Patient, pancreas, and kidney survivals overlapped at 1- and 3-years posttransplant, namely all 95.4% for the Neoral arm compared with 95.8%, 91.8%, and 95.8%, respectively, for the Prograf arm (P.05).We conclude that in MMF-based immunosuppression there is no convincing evidence that Prograf should be preferred to Neoral in SPKTx.