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Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease characterised by epistaxis. Surgical procedures for epistaxis vary from diathermocoagulation to nasal closure. The aim of this paper is to report our experience in endoscopic surgical management of epistaxis in HHT patients.This is a descriptive, longitudinal study carried out at the Otorhinolaryngology Department of IRCCS Policlinico San Matteo in Pavia, a reference centre for the treatment and diagnosis of HHT. We retrospectively evaluated HHT patients who underwent surgery for epistaxis from 1996 to 2015, including only those treated with endoscopic surgery.Among the 591 patients hospitalised and screened for HHT, 323 (54.7%) underwent endoscopic surgery for epistaxis, for a total of 679 procedures. General anaesthesia was used in 77.2% of procedures; argon plasma coagulation was the instrument of choice in the majority of patients, followed by lasers and quantum molecular resonance technology.We report one of the largest cohorts undergoing endoscopic treatment of epistaxis in HHT patients. This mini-invasive surgical treatment allowed us to control epistaxis without major complications and nasal packaging and can be repeated over time. For these reasons, we recommend it as first choice in case of epistaxis in HHT patients.Il trattamento endoscopico dell’epistassi nella teleangectasia emorragica ereditaria: la nostra esperienza.L’obiettivo di questo studio è riportare la nostra esperienza nel trattamento endoscopico dell’epistassi nei pazienti con Teleangectasia Emorragica Ereditaria (HHT).Si tratta di uno studio longitudinale retrospettivo svolto presso l’UOC di Otorinolaringoiatria della Fondazione IRCCS Policlinico San Matteo di Pavia, centro di riferimento per la diagnosi e la cura dell’HHT. Sono stati valutati i pazienti sottoposti dal 1996 al 2015 a trattamento chirurgico delle epistassi ricorrenti, includendo solo quelli trattati con tecnica endoscopica.Dei 591 pazienti ricoverati e sottoposti a screening per HHT, 323 (54.7%) sono stati sottoposti a trattamento chirurgico endoscopico per epistassi, per un totale di 679 procedure. Il 77,2% delle procedure è stato eseguito in anestesia generale; il sistema ad Argon Plasma è stato lo strumento di scelta nella maggior parte dei pazienti, seguito dai laser e dalla quantum molecular resonance.Riportiamo una delle più ampie casistiche nel trattamento endoscopico dell’epistassi nei pazienti con HHT. Tale approccio consente di gestire i pazienti senza necessità di tamponamento nasale, è scevro da complicanze maggiori, ripetibile nel tempo e riteniamo che debba essere preso in considerazione come trattamento di prima scelta in caso di epistassi in pazienti con HHT.

Objectives The main aim was to assess the performance and cutoff value for the detection of liver steatosis (grade S > 0) with the Attenuation Imaging–Penetration (ATI‐Pen) algorithm available on the Aplio i‐series ultrasound systems (Canon Medical Systems, Otawara, Japan). The magnetic resonance imaging–derived proton density fat fraction (MRI‐PDFF) was used as the reference standard. Secondary aims were to compare the results to those obtained with the previous ATI algorithm (Attenuation Imaging–General [ATI‐Gen]) and with the controlled attenuation parameter (CAP) and to generate a regression equation between ATI‐Pen and ATI‐Gen values. Methods Consecutive adult patients potentially at risk of liver steatosis were prospectively enrolled. Each patient underwent ultrasound quantification of liver steatosis with ATI‐Pen and ATI‐Gen and a CAP assessment with the FibroScan system (Echosens, Paris, France). The MRI‐PDFF evaluation was performed within a week. The correlations between ATI‐Pen, ATI‐Gen, the CAP, and the MRI‐PDFF were analyzed with the Pearson rank correlation coefficient. The diagnostic performance of ATI‐Pen, ATI‐Gen, and the CAP was assessed with receiver operating characteristic curves and an area under the receiver operating characteristic curve (AUROC) analysis. Results Seventy‐two individuals (31 male and 41 female) were enrolled. Correlation coefficients of ATI‐Pen, ATI‐Gen, and the CAP with the MRI‐PDFF were 0.78, 0.83, and 0.58, respectively. The AUROCs of ATI‐Pen, ATI‐Gen, and the CAP for detecting steatosis (S > 0) were 0.90 (95% confidence interval, 0.81–0.96), 0.92 (0.82–0.98), and 0.85 (0.74–0.92), and the cutoffs were greater than 0.69 dB/cm/MHz, greater than 0.62 dB/cm/MHz, and greater than 273 dB/m. The regression equation between ATI‐Pen and ATI‐Gen was ATI‐Pen = 0.88 ATI‐Gen + 0.13. Conclusions Attenuation Imaging is a reliable tool for detecting liver steatosis, showing an excellent correlation with the MRI‐PDFF and high performance with AUROCs of 0.90 or higher., Access the CME test here and search by article title.

Preterm very low birth weight infants (VLBWi) are known to be at greater risk of adverse neurodevelopmental outcome. Identifying early factors associated with outcome is essential in order to refer patients for early intervention. Few studies have investigated neurodevelopmental outcome in Italian VLBWi. The aim of our longitudinal study is to describe neurodevelopmental outcome at 24 months of corrected age in an eleven-year cohort of 502 Italian preterm VLBWi and to identify associations with outcome. At 24 months, Griffiths’ Mental Developmental Scales were administered. Neurodevelopmental outcome was classified as: normal, minor sequelae (minor neurological signs, General Quotient between 76 and 87), major sequelae (cerebral palsy; General Quotient ≤ 75; severe sensory impairment). 75.3% showed a normal outcome, 13.9% minor sequelae and 10.8% major sequelae (3.8% cerebral palsy). Male gender, bronchopulmonary dysplasia, abnormal neonatal neurological assessment and severe brain ultrasound abnormalities were independently associated with poor outcome on multivariate ordered logistic regression. Rates of major sequelae are in line with international studies, as is the prevalence of developmental delay over cerebral palsy. Analysis of perinatal complications and the combination of close cUS monitoring and neurological assessment are still essential for early identification of infants with adverse outcome.

OBJECTIVES: The primary aim of this study was to investigate the value of attenuation imaging (ATI), a novel ultrasound technique for detection of steatosis, by comparing the results to that obtained with controlled attenuation parameter (CAP) and by using MRI-derived proton density fat fraction (PDFF) as reference standard. METHODS: From March to November 2018, 114 consecutive adult subjects potentially at risk of steatosis and 15 healthy controls were enrolled. Each subject underwent ATI and CAP assessment on the same day. MRI-PDFF was performed within a week. RESULTS: The prevalence of steatosis, as defined by MRI-PDFF ≥ 5%, was 70.7%. There was a high correlation of ATI with MRI-PDFF (r = 0.81, P < 0.0001). The correlation of CAP with MRI-PDFF and with ATI, respectively, was moderate (r = 0.65, P < 0.0001 and r = 0.61, P < 0.0001). The correlation of ATI or CAP with PDFF was not affected by age, gender, or body mass index. Area under the receiver operating characteristics of ATI and CAP, respectively, were 0.91 (0.84–0.95; P < 0.0001) and 0.85 (0.77–0.91; P < 0.0001) for detecting S > 0 steatosis (MRI-PDFF ≥ 5%); 0.95 (0.89–0.98; P < 0.0001) and 0.88 (0.81–0.93; P < 0.0001) for detecting S > 1 steatosis (MRI-PDFF ≥ 16.3%). The cutoffs of ATI and CAP, respectively, were 0.63 dB/cm/MHz and 258 dB/m for detecting S > 0 liver steatosis; 0.72 dB/cm/MHz and 304 dB/m for detecting S > 1 steatosis. ATI performed better than CAP, and this improvement was statistically significant for S > 1 (P = 0.04). DISCUSSION: This study shows that, in patients with no fibrosis/mild fibrosis, ATI is a very promising tool for the noninvasive assessment of steatosis.

Lembo d’avambraccio radiale vs lembo d’avambraccio ulnare: uno studio preliminare sulla morbilità del sito donatore.L’obiettivo di questo studio era di confrontare la morbilità del sito donatore dopo chirurgia ricostruttiva con il lembo libero d’avambraccio ulnare (UFFF) e il lembo libero d’avambraccio radiale (RFFF) con metodiche soggettive. Il UFFF e il RFFF sono stati utilizzati per la ricostruzione del difetti dei tessuti molli della testa e del collo in 30 pazienti (20 M e 10 F; range d’età 28-75 anni), affetti da carcinoma squamocellulare della testa e del collo. Il questionario sulla disabilità per l’arto superiore DASH è stato usato per valutare la morbilità del sito donatore. L’analisi del punteggio DASH dei pazienti ha dimostrato una mediana del punteggio totale DASH di 9,17. Non sono state osservate differenze significative per i valori mediani dei gruppi RFFF e UFFF (7,14 vs 10, rispettivamente) e per i valori ottenuti dai maschi e dalle femmine (5 vs 13,3, rispettivamente). Il UFFF può essere considerato una valida alternativa al RFFF per la ricostruzione dei difetti dei tessuti molli del distretto testa-collo; è affidabile, semplice da trapiantare e non causa maggiori morbilità del sito donatore come dimostrato dal questionario DASH.The objective of this study was to compare donor site morbidity after reconstructive surgery with Ulnar Forearm Free Flap (UFFF) and Radial Forearm Free Flap (RFFF) with subjective methods. The UFFF and the RFFF were applied for reconstruction of soft tissue defects of the head and neck region in 30 patients (20 M and 10 F; age range 28-75 years) affected by head and neck squamous cell carcinoma. The Disability of Arm, Shoulder and Hand (DASH) questionnaire was used to assess morbidity of the donor site. Analysis of the patients’ DASH scores showed an overall median DASH total score of 9.17. No significant differences were observed for median values of the RFFF and UFFF groups (7.14 vs 10 respectively) or for the values in males and females (5 vs 13.3 respectively). The UFFF can be considered a valid alternative to the RFFF for reconstruction of soft tissue defects of the head and neck area; it is safe, easy to harvest and is not associated with major morbidities of the donor site as demonstrated by the DASH questionnaire.

rigid trocars are widely adopted in video-assisted thoracic surgery (VATS), despite some disadvantages: (I) cannula strong pressure on intercostal nerve stimulating postoperative pain; (II) limited movement of thoracoscopic devices on their fulcrum when extreme acute angles with the chest wall are needed. Wound retractor (WR) device, designed for laparoscopic surgery, it is also used in VATS, but to protect mini-thoracotomy. We compared the use of extra-small WR versus rigid trocar at camera port that is the most painful thoracostomy. The aim was to determine if WR is associated with less postoperative pain and better scope maneuverability.This is a single institution prospective study recorded and approved by ethics committee at our hospital. From October 2016 to June 2017, we enrolled 40 patients (statistical power 88%), randomized into two different groups. Group A (20 patients) underwent VATS lung resection using WR at camera port, group B (20 patients) using rigid trocar. Intra-operative data collected were maximum acute angle obtained between the camera and chest wall and chest wall thickness. Pain was measured by numerical analog scales (NAS) at 6, 12, 24, 48 and 72 hours after surgery. We also measured total morphine consumption at 72 h administered by patient controlled analgesia (PCA) system.No statistical significance was found in the demographic traits of the two groups (P=1). Statistically significant differences were found in favor of group A for both pain control, morphine consumption (P0.001) and camera maneuverability (described as maximum acute angle obtained/chest wall thickness) (P0.001).patients who had WR showed less postoperative pain. Moreover, WR presented other advantages: camera protection by small bleeding from chest wall, adaptability with every chest wall thickness, absence of skin injury around the port. We suggest its use instead of rigid trocar.

The decisional balance inventory (DBI) test is a valuable tool to assess motivation to change; we consider its application in enhancing motivation of losing weight. Our aim is the translation, cultural adaption and validation in Italian of this test originally designed and drafted in English. The questionnaire has been translated according to an English → Italian → Italian → English algorithm with reconciliation of the differences. Pilot study and retests were performed on 47 cases [body mass index (BMI) ≥30 kg/m2] and 15 controls (BMI value between 18.5 and 25 kg/m2). The internal consistency of the Italian version of DBI test, was satisfied (Cronbach α 0.87 on patients); test-retest shows a good concordance in pilot [Lin’s concordance correlation coefficient (CCC) 0.79; 95% confidence interval (CI) 0.68-0.90] and in patient sample (Lin’s CCC 0.83; 95% CI: 0.67 0.99).Our study demonstrated the trans-cultural adaptation and validation of DBI test in Italian.

BACKGROUND: Epidural infusion of levobupivacaine and ropivacaine provides adequate postoperative pain management by minimizing side effects related to IV opioids and improving patient outcome. The safety profile of different drugs can be better estimated by comparing their pharmacokinetic profiles than by considering their objective side effects. Because levobupivacaine and ropivacaine have different pharmacokinetic properties, our aim was to investigate whether there is a difference in the pharmacokinetic variability of the 2 drugs in a homogeneous population undergoing continuous epidural infusion. This double-blind, multicenter, randomized, controlled trial study was designed to compare the pharmacokinetics of continuous thoracic epidural infusion of levobupivacaine 0.125% or ropivacaine 0.2% for postoperative pain management in adult patients who had undergone major abdominal, urological, or gynecological surgery. This study is focused on the evaluation of the coefficient of variation (CV) to assess the equivalence in the systemic exposure and interindividual variability between levobupivacaine and ropivacaine and, therefore, the possible differences in the predictability of the plasmatic concentrations of the 2 drugs during thoracic epidural infusion. METHODS: One hundred eighty-one adults undergoing major abdominal surgery were enrolled in the study. Patients were randomized to receive an epidural infusion of levobupivacaine 0.125% + sufentanil 0.75 μg/mL or of ropivacaine 0.2% + sufentanil 0.75 μg/mL at 5 mL/h for 48 hours. The primary end point of this study was to analyze the variability of plasma concentration of levobupivacaine and ropivacaine via an area under the curve within a range of 15% of the CV during 48 hours of continuous epidural infusion. The CV shows how the concentration values of local anesthetics are scattered around the median concentration value, thus indicating the extent to which plasma concentration is predictable during infusion. Secondary end points were to assess the pharmacologic profile of the local anesthetics used in the study, including an analysis of mean peak plasma concentrations, and also to assess plasma clearance, side effects, pain intensity (measured with a verbal numeric ranging score, i.e., static Numeric Rating Scale [NRS] and dynamic NRS]), and the need for rescue doses. RESULTS: The comparison between the 2 CVs showed no statistical difference: the difference between area under the curve was within the range of 15%. The CV was 0.54 for levobupivacaine and 0.51 for ropivacaine (P = 0.725). The plasma concentrations of ropivacaine approached the Cmax significantly faster than those of levobupivacaine. Clearance of ropivacaine decreases with increasing patient age. There were no significant differences in NRS, dynamic NRS scores, the number of rescue doses, or in side effects between groups. CONCLUSIONS: Considering the CV, the interindividual variability of plasma concentration for levobupivacaine and ropivacaine is equivalent after thoracic epidural infusion in adults. We found a reduction in clearance of ropivacaine depending on patient age, but this finding could be the result of some limitations of our study. The steady-state concentration was not reached during the 48-hour infusion and the behavior of plasma concentrations of ropivacaine and levobupivacaine during continuous infusions lasting more than 48 hours remains to be investigated, because they could reach toxic levels. Finally, no differences in the clinical efficacy or in the incidence of adverse effects between groups were found for either local anesthetic., Published ahead of print May 14, 2015

To evaluate the inter-device reproducibility of retrobulbar blood flow measurements obtained by two commercially available CDI (color Doppler imaging) devices.The right eyes of 10 healthy volunteers were investigated. Four examiners, namely two ophthalmologists and two radiologists, performed CDI examination of the ophthalmic artery, central retinal artery and temporal short posterior ciliary arteries using both CDI devices: ESAOTE MYLAB™ and SIEMENS ANTARES STELLAR PLUS™. The peak systolic velocity (PSV), the end-diastolic velocity (EDV) and the resulting resistivity index (RI) were averaged for 3 cardiac cycles. To evaluate the reproducibility between both device measurements, the Lin's concordance correlation coefficient (CCC) was used. CCC can be expressed as the product of Pearson's r (the measure of precision) and C_b (the measure of accuracy).Results show that the inter-device reproducibility for CDI measurements is not acceptable since a poor degree of overall concordance (0.15CCC0.37) was obtained: accuracy was high (C_b 0.71) but overall precision low (0.18Pearson's r0.47). Ophthalmologists and radiologists obtained similar results.To evaluate the causal role of blood flow abnormalities in glaucoma, CDI analysis using different devices seems unreliable. CDI inter-device reproducibility seems unrelated to medical speciality of the examiners. However, to improve present results, the use of similar probes and standardized CDI instrument settings as well as a CDI images analysis by a single grader, might possibly improve the inter-device reproducibility when testing the retrobulbar blood flow velocity.Valutare la riproducibilità delle misurazioni delle velocità di flusso ematico nei vasi retrobulbari di volontari sani: le misurazioni sono state ottenute con due diverse strumentazioni ecografiche commercialmente disponibili.Quattro operatori, due radiologi e due oculisti, hanno misurato le velocità di flusso nell’arteria oftalmica (AO), nell’arteria centrale della retina (ACR) e nelle arterie ciliari posteriori brevi (ACPB) in 10 occhi di volontari sani utilizzando due ecografi: ESAOTE MYLAB™ and SIEMENS ANTARES STELLAR PLUS™. Sono state calcolate le medie di 3 cicli cardiaci dei parametri di flusso PSV (velocità di picco sistolico), EDV (velocità di fine diastole) e IR (indice di resistività). Per valutare la riproducibilità delle misure effettuate con le due strumentazioni è stato calcolato il coefficiente di correlazione di Lin (CCC). Il CCC può essere espresso come il prodotto del coefficiente di Pearson’s r (misura della precisione) e C_b (misura dell’accuratezza).I risultati mostrano che la riproducibilità delle misurazioni tra due ecografi non è accettabile dal momento che è stato ottenuto uno scarso grado di concordanza (0.15CCC0.37): il grado di accuratezza è alto (C_b 0.71) mentre il grado di precisione basso (0.18Pearson’s r0.47). Oculisti e radiologi hanno ottenuto risultati simili.Per valutare il ruolo causale delle anomalie di flusso ematico nella patogenesi della neuropatia ottica glaucomatosa l’utilizzo di diverse strumentazioni ecografiche appare inaffidabile. La riproducibilità delle misurazioni ottenute con diversi macchinari non sembra correlata con la specialità medica dell’esaminatore. L’uso di sonde simili, di settings CDI standardizzati e l’analisi delle immagini da parte di un singolo operatore potrebbero essere accorgimenti adeguati per migliorare i risultati attuali e quindi per migliorare la riproducibilità inter-device delle velocità di flusso nei vasi retrobulbari.

Background The role of CD4+CD25highCD127− T-reg cells in solid-organ Transplant (Tx) acceptance has been extensively studied. In previous studies on kidney and liver recipients, peripheral T-reg cell counts were associated to graft survival, while in lung Tx, there is limited evidence for similar findings. This study aims to analyze long term peripheral kinetics of T-reg-cells in a cohort of lung recipients and tests its association to several clinical variables. Methods From jan 2009 to dec 2014, 137 lung Tx recipients were submitted to an immunological follow up (median: 105.9 months (6.7–310.5)). Immunological follow up consisted of a complete blood peripheral immuno-phenotype, inclusive of CD4+CD25highCD127− T and FOXP3+ cells. We tested the association between T-reg and relevant variables by linear OR regression models for repeated measures, adjusting for time from Tx. Also, by ordered logistic models for panel data, the association between Chronic Lung Allograft Dysfuncton (CLAD) onset/progression and T-reg counts in the previous 3 months was tested. Results Among all variables analyzed at multivariate analysis: Bronchiolitis Obliterans Syndrome (OR −6.51, p

The clinical course of IgA nephropathy (IgAN) and its outcome are extremely variable. Proteinuria at baseline has been considered one of the most important risk factors. More recently, mean proteinuria of follow-up (time-average proteinuria: TAp) was described as a stronger marker of renal survival, suggesting to consider it as a marker of disease activity and response to treatment. We evaluated predictors of renal survival in IgAN patients with different degrees of renal dysfunction and histological lesions, focusing on the role of the therapy in influencing TAp. We performed a retrospective analysis of three prospective, randomized, clinical trials enrolling 325 IgAN patients from 1989 to 2005. Patients were divided into 5 categories according to TAp. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16.6%) and renal survival was much better in groups having lower TAp. The median follow up was 66.6 months (range 12 to 144). The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16,6%) and renal survival was much better in groups having lower TA proteinuria. At univariate analysis plasma creatinine and 24h proteinuria, systolic (SBP) and diastolic (DBP) blood pressure during follow-up and treatment with either steroid (CS) or steroid plus azathioprine (CS+A) were the main factors associated with lower TAp and renal survival. At multivariate analysis, female gender, treatment with S or S+A, lower baseline proteinuria and SBP during follow-up remained as the only variables independently influencing TAp. In conclusion, TA-proteinuria is confirmed as one of the best outcome indicators, also in patients with a severe renal insufficiency. A 6-month course of corticosteroids seems the most effective therapy to reduce TAp.

[This corrects the article DOI: 10.1007/s40477-016-0194-5.].

Objective Sialic-acid-binding immunoglobulin-like lectin-7 (Siglec-7) is a natural killer (NK) cell inhibitory receptor associated with NK phenotypic and functional abnormalities in HIV-1 infection. We investigated the significance of NK-expressed and serum soluble Siglec-7 in relation to NK functional ability and parameters of liver necroinflammation and fibrosis in chronic HCV infection. Design NK-expressed and serum Siglec-7 were evaluated in 130 and 166 HCV-infected individuals by flow cytometry and ELISA, respectively. NK cell degranulation and cytokine secretion were determined by flow cytometry. 65 patients with chronic HBV infection, 84 with chronic biliary disorders and 168 healthy donors served as controls. Results Expression of Siglec-7 was significantly decreased on NK cells from HCV-infected and HBV-infected patients and, conversely, serum Siglec-7 was significantly increased in these patients compared with controls. The frequency of Siglec-7pos NK cells was significantly higher at baseline in sustained virological responders to pegylated interferon-α/ribavirin treatment than in non-responders. Activating receptor expression was significantly higher in Siglec-7pos NK cells and was associated with increased degranulation and cytokine secretion compared with Siglec-7 neg cells. In chronic HCV infection, there was an inverse correlation between Siglec-7 expression and serum aminotransferases, γ-glutamyl transpeptidase, liver stiffness, aspartate aminotransferase to platelet ratio index and fibrosis-4 scores, and a positive correlation between serum Siglec-7 and the same clinical parameters, including histological staging. Conclusions These findings identify Siglec-7 neg NK cells as a dysfunctional subpopulation associated with severe liver disease in chronic HCV infection.

Diagnosis of gastro-esophageal reflux disease (GERD) is mainly based on symptom evaluation, possibly coupled with various invasive investigations (endoscopy, pH-metry, and impedance). New input has recently come from histology: in this context, the diagnostic role of inflammatory cells other than eosinophils and neutrophils is still debated. Aim of the study is to evaluate the diagnostic relevance of intraepithelial lymphocytes, mast cells, and Langerhans cells in GERD-associated microscopic esophagitis (GAME). Twenty healthy volunteers and 119 patients with GERD symptoms were prospectively recruited and subdivided, on the basis of endoscopy and pH-metry, in erosive (ERD, 48) and non-erosive disease (NERD, 71). Biopsy samples at 2 cm above the Z-line and at Z-line were evaluated for GERD-associated histological lesions (basal cell hyperplasia, papillae elongation, intercellular space dilatation, intraepithelial eosinophils, and neutrophils). Immunohistochemistry for T lymphocytes (CD3, CD4, CD8), B lymphocytes (CD20), NK cells (CD56), macrophages (CD68), mast cells (c-Kit), and Langerhans cells (S100) was performed. Among inflammatory cells, only intraepithelial T lymphocytes (ITLs) showed statistical correlation with the other histological lesions both in ERD and NERD. ITLs distinguished GERD patients from controls with good sensitivity and specificity (85.5 and 85 % at 2 cm above Z-line; 89.5 and 75 % at Z-line) when a cut-off of 20 cells was applied. An analysis of the T subpopulations found a CD4+/CD8+ ratio close to 1:1; B cells, mast cells, Langerhans cells, NK cells, and macrophages showed a limited role in GERD. ITL evaluation represents an additional useful parameter in the histological evaluation of GAME.

Background and study aims: The HER2 status of small endoscopic biopsies is important for predicting the eligibility of patients with metastatic HER2-positive gastric cancer or gastro-esophageal junction (GEJ) cancer for anti-HER2 therapy approved by the U.S. Food and Drug Administration. The aim of this study was to identify the minimum biopsy set required to evaluate the HER2 status with confidence. Patients and methods: A total of 103 consecutive patients with resected gastric cancer or GEJ cancer were retrospectively selected; 2 formalin-fixed, paraffin-embedded samples of each surgical specimen and all paired endoscopic biopsies were analyzed for HER2 status with both immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) methods. A total of 10 virtual biopsies were constructed by selecting areas 2.6 mm in diameter on the luminal side of digitalized slides obtained from the surgical specimens. The results of evaluating HER2 status in virtual biopsies, slides containing complete surgical specimens, and endoscopic biopsies were compared. The resulting minimum biopsy set was applied to the endoscopic biopsy series for validation. Results: A biopsy set containing a minimum of 5 samples was identified as the most accurate in predicting HER2 status (sensitivity, 92 %; specificity, 97 %). In only 3 of the 103 cases (2.9 %) did a comparison of the HER2 evaluation of virtual biopsies and that of entire slides show inconsistent results. Overall agreement between the endoscopic biopsies and surgical samples for HER2 IHC status increased from 78.4 % to 92.3 % when biopsy sets containing 4 or fewer samples were compared with biopsy sets containing 5 or more samples. Conclusions: Although the recommendations suggest that 8 to 10 biopsies are necessary, the results show that a minimum set of 5 biopsies may be sufficient for reliable HER2 assessment in gastric cancer and GEJ cancer. However, endoscopists should be aware that a smaller sample size may be less accurate in selecting patients eligible for anti-HER2 therapy.

Objective To evaluate whether rituximab at a low dose of 250 mg/m 2 × 2 may be as effective as at higher dosages, most commonly 375 mg/m 2 × 4, used in previous studies on the treatment of patients with refractory mixed cryoglobulinemia (MC) vasculitis associated with hepatitis C virus (HCV) infection. Methods We conducted a phase 2, single-arm two-stage trial (EUDRACT n. 2008-000086-38) of low-dose rituximab in 52 patients with HCV-associated MC who were ineligible/intolerant or non-responder to antiviral therapy. The primary outcomes were response of vasculitis evaluated by the Birmingham Vasculitis Activity Score (BVAS) at months 3, 6 and 12, rate of relapses and time to relapse, and rate of adverse events. Our data were compared with those reported in 19 published studies selected among 291 reviewed in a literature search. Results The cumulative response rate (complete and partial) at month 3 was 81% in our patients, and 86% in 208 patients from studies using high-dose rituximab. The relapse rate and median time to relapse were, respectively, 41% and 6 months in our study, and 32% and 7 months in high-dose studies. Treatment-related adverse events were 11.5% in our study and 19.9% in high-dose studies. None of these differences was statistically significant. Conclusion Rituximab at a low dosage of 250 mg/m 2 × 2 is as effective as at higher dosages for treating MC vasculitis. This low-dose regimen may improve the cost/benefit profile of rituximab therapy for MC.

This study was done to evaluate the intra- and inter-operator reproducibility of colour Doppler imaging (CDI) in assessing blood flow velocity in the ophthalmic (OA), central retinal (CRA) and short posterior ciliary arteries (SPCA) in healthy subjects. The right eye of two groups of eight healthy volunteers was examined. Two radiologists and two ophthalmologists, divided into pairs, measured peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistivity index (RI) of each vessel using a different CDI device for each group. The concordance between two measurements was evaluated with Lin’s concordance correlation coefficient (CCC). Globally, very good degrees of intra-operator concordance were obtained for the PSV (0.859 cm/s), EDV (0.834 cm/s) and RI (0.859) of the OA. There was moderate concordance for PSV (0.574 cm/s) and EDV (0.594 cm/s) and good concordance for RI (0.694) for the CRA. Good degrees of concordance were obtained for the SPCA measurements. However, inter-operator concordance was found globally poor. These data show that CDI measurements in retrobulbar vessels are operator dependent. To increase the intra-operator and inter-operator concordance, rules should be adopted for timing of the examination and positioning of the probe to minimise the pressure applied on the eye.

Alpha1-antitrypsin Deficiency (AATD) is a rare hereditary disorder with an estimated prevalence of about 1/5000 individuals in Italy. Deficient patients are at a higher risk of developing lung emphysema and chronic liver disease. The low estimated prevalence of AATD prompted the establishment of a registry with the aim of learning more about the natural history and the quality of care of these patients. The Italian registry for AATD was established in 1996. In this study, genetic and clinical findings of Italian AATD patients are presented. Moreover, we also evaluated the changes in health-related quality of life (HRQoL) in patients with COPD and AAT deficiency over a three-year period, in relation to augmentation therapy. In a period spanning 18 years (1996-2014) a total of 422 adult subjects with severe AATD were enrolled, namely 258 PI*ZZ, 74 PI*SZ, 4 PI*SS and 86 patients with at least one rare deficient allele. The 21.3% frequency for AATD patients with at least one deficient rare variant is the highest so far recorded in national registries of AATD. The registry data allow a detailed characterization of the natural course of the disease and the level of patient care, as well as confirm the usefulness of early AATD detection.

AIM: To assess the performance of controlled attenuation parameter (CAP) in patients with chronic viral hepatitis. METHODS: CAP is a new technique that measures the attenuation in the liver of an ultrasound beam, which is directly related to lipid accumulation. Consecutive patients undergoing liver biopsy for chronic viral hepatitis were studied using the M probe of FibroScan device (Echosens, Paris, France). The device estimates liver steatosis in decibel per meter (dB/m). An expert operator performed all measurements. Steatosis was graded according to Kleiner’s classification. Pearson or Spearman rank coefficient was used to test correlation between two study variables. Linear regression was used for multivariate model to assess the association between CAP and other variables. Receiver operating characteristic curve analysis was performed to calculate area under the curve (AUROC) for S0 vs S1-S3 and S0-S1 vs S2-S3. RESULTS: 115 subjects (85 males and 30 females) were prospectively studied. The mean values of CAP were 227.1 ± 43.1 for S0; 254.6 ± 38.9 for S1; 297.8 ± 49.4 dB/m for S2-S3. In univariate analysis CAP showed a significant correlation with age, body mass index (BMI), degree of steatosis, and cholesterol. Multivariate regression analysis confirmed the correlation with the degree of steatosis [coefficient, 1.2 (0.60-1.83); P < 10-5] and BMI [coefficient, 4.1 (0.5-7.8); P = 0.03] but not with all other variables. Optimal cutoff values for S ≥ 1 and S ≥ 2 were 219 dB/m [AUROC, 0.76 (0.67-0.84); sensitivity, 91.1% (78.8-97.5); specificity, 51.6% (38.7-64.2); positive predictive value, 56.9% (44.7-68.6); negative predictive value, 89.2% (74.3-97.0); positive likelihood ratio, 1.88 (1.4-2.5); negative likelihood ratio, 0.17 (0.07-0.5)] and 296 dB/m [AUROC, 0.82 (0.74-0.89); sensitivity, 60.0% (32.3-83.7); specificity, 91.5% (83.9-96.3); positive predictive value, 52.9% (27.8-77.0); negative predictive value, 93.5% (86.3-97.6); positive likelihood ratio, 7.05 (3.2-15.4); negative likelihood ratio, 0.44 (0.2-0.8)], respectively. CONCLUSION: Controlled attenuation parameter could be a useful tool in the clinical management of patients with chronic viral hepatitis for detecting liver steatosis.

AIM: To estimate the validity of the point shear-wave elastography method by evaluating its reproducibility and accuracy for assessing liver stiffness. METHODS: This was a single-center, cross-sectional study. Consecutive patients with chronic viral hepatitis scheduled for liver biopsy (LB) (Group 1) and healthy volunteers (Group 2) were studied. In each subject 10 consecutive point shear-wave elastography (PSWE) measurements were performed using the iU22 ultrasound system (Philips Medical Systems, Bothell, WA, United States). Patients in Group 1 underwent PSWE, transient elastography (TE) using FibroScan (Echosens, Paris, France) and ultrasound-assisted LB. For the assessment of PSWE reproducibility two expert raters (rater 1 and rater 2) independently performed the examinations. The performance of PSWE was compared to that of TE using LB as a reference standard. Fibrosis was staged according to the METAVIR scoring system. Receiver operating characteristic curve analyses were performed to calculate the area under the receiver operating characteristic curve (AUC) for F ≥ 2, F ≥ 3 and F = 4. The intraobserver and interobserver reproducibility of PSWE were assessed by calculating Lin’s concordance correlation coefficient. RESULTS: To assess the performance of PSWE, 134 consecutive patients in Group 1 were studied. The median values of PSWE and TE (in kilopascals) were 4.7 (IQR = 3.8-5.4) and 5.5 (IQR = 4.7-6.5), respectively, in patients at the F0-F1 stage and 3.5 (IQR = 3.2-4.0) and 4.4 (IQR = 3.5-4.9), respectively, in the healthy volunteers in Group 2 (P < 10-5). In the univariate analysis, the PSWE and TE values showed a high correlation with the fibrosis stage; low correlations with the degree of necroinflammation, aspartate aminotransferase and gamma-glutamyl transferase (GGT); and a moderate negative correlation with the platelet count. A multiple regression analysis confirmed the correlations of both PSWE and TE with fibrosis stage and GGT but not with any other variables. The following AUC values were found: 0.80 (0.71-0.87) for PSWE and 0.82 (0.73-0.89) for TE (P = 0.42); 0.88 (0.80-0.94) for PSWE and 0.95 (0.88-0.98) for TE (P = 0.06); and 0.95 (0.89-0.99) for PSWE and 0.92 (0.85-0.97) for TE (P = 0.30) for F ≥ 2, F ≥ 3 and F = 4, respectively. To assess PSWE reproducibility, 116 subjects were studied, including 47 consecutive patients scheduled for LB (Group 1) and 69 consecutive healthy volunteers (Group 2). The intraobserver agreement ranged from 0.83 (95%CI: 0.79-0.88) to 0.96 (95%CI: 0.95-0.97) for rater 1 and from 0.84 (95%CI: 0.79-0.88) to 0.96 (95%CI: 0.95-0.97) for rater 2. The interobserver agreement yielded values from 0.83 (95%CI: 0.78-0.88) to 0.93 (95%CI: 0.91-0.95). CONCLUSION: PSWE is a reproducible method for assessing liver stiffness, and it compares with TE. Compared with patients with nonsignificant fibrosis, healthy volunteers showed significantly lower values.

Mineral and bone disorders (MBD) in patients undergoing hemodialysis (HD) are a major clinical complication. Current therapeutic strategies do not attain the expected results. The Italian audit on mineral metabolism was implemented to investigate MBD management through a “patient-oriented” approach. Clinical and laboratory data pertinent to MBD from 509 prevalent adult patients on chronic HD were recorded and examined (audit), after which individual strategies were elaborated to improve MBD control. Their effectiveness was evaluated 6 months after the audit (Post-6). The audit disclosed poor MBD control in a high percentage of patients (56 %). Low compliance to treatment was the major determinant of failure (in 43.5 % of cases). Logistic regression showed a direct correlation between high degree of compliance and the achievement of therapeutic targets, e.g. parathyroid hormone: odds ratio (OR) 2.48, p = 0.015. In contrast, a minority of the proposed interventions (14.7 %) included strategies to improve patient compliance. At Post-6, despite a significant increase in drug prescription (p

Aims. To evaluate thirteen years of hyoid suspension experience in multilevel OSAHS surgery, for which hyoidthyroidpexia represented the exclusive hypopharyngeal approach applied.Materials and Methods. From 1998 to 2011, a bicentric retrospective study was conducted: all adult patients with a diagnosis of OSAHS were enrolled. Specific eligible criteria were established. Pre-/postoperative data concerning ENT and sleep findings were recorded. Recruited subjects were surveilled for a follow-up range from 6 to 18 months.Results. A total of 590 hyoid suspensions were evaluated, but only 140 patients met the specific inclusion criteria. A success rate of 67% was obtained. No intraoperative adverse events or major complications occurred. Excessive daytime sleepiness was observed in 28% of nonresponders. Despite the homogeneous candidate anatomy, ENT awake findings changed differently after surgery. Statistical analysis revealed multilevel surgery to be more effective when AHI < 30. Postoperative AHI was statistically not influenced by preoperative BMI.Conclusions. Hyoid suspension in multilevel treatment is effective when short-term results are considered. The necessity of a more valuable anatomic-based diagnostic approach is crucial to guide the patient selection. Long-term followups and randomized prospective trials with case-control series are needed to increase the level of evidence of this surgery.

Background Knowledge of the role of the receptor for advanced glycation end products (RAGE), particularly its soluble form (sRAGE), and of its advanced glycation end product (AGE) ligand, N-(carboxymethyl)lysine adducts (CML), is limited in chronic heart failure (CHF) and in chronic obstructive pulmonary disease (COPD). We evaluated whether the AGE/RAGE system is activated in stable CHF and COPD, and whether plasma sRAGE and CML levels are affected by clinical and functional parameters. Materials and methods We measured plasma levels of sRAGE and CML using a sandwich enzyme-linked immunosorbent assay (ELISA) in 143 subjects, aged ≥ 65 years, divided into five groups: 58 with CHF, 23 with COPD, 27 with CHF+COPD and 35 controls (17 healthy smokers and 18 healthy nonsmokers). Individuals with diabetes were excluded from the study. Results Plasma levels of sRAGE and CML were higher in CHF patients than in controls [sRAGE: 0·48 (0·37–0·83) vs. 0·42 (0·29–0·52) ng/mL, P = 0·01; CML: 1·95 (1·58–2·38) vs. 1·68 (1·43–2·00) ng/mL, P = 0·01]. By contrast, sRAGE and CML were not different between both COPD and CHF+COPD patients and controls (P > 0·05). N-terminal pro-brain natriuretic peptide (Nt-pro BNP) correlated with sRAGE, but not with CML, in the patient groups: CHF (r = 0·43, P