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Objective: Preeclampsia (PE) is the major cause of maternal morbidity and mortality and the leading cause of premature delivery worldwide. As well as intrauterine growth restriction (IUGR), PE is associated with patho-genic evidence of placental malperfusion and ischemia. Recent literature has highlighted the potential of pra-vastatin in the prevention and treatment of these conditions. Aim of this study is to describe perinatal outcomes and placental histopathological findings in a small series of pregnant women with severe PE and IUGR treated with pravastatin on compassionate grounds. Two-year follow up of these babies is provided.Study design: Between October 2017 and October 2019 in Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy, women with singleton pregnancy between 19.6 and 27.6 gestational weeks, who presented with severe PE and IUGR were counselled for a compassionate treatment with Pravastatin 40 mg a day. Treated women were compared with controls identified with similar data in terms of gestational age at diagnosis, clinical maternal data, Doppler severity findings. Neonates were followed up for two years.Results: The median time from diagnosis to delivery was 39 days (IQR 20) for women in the pravastatin group and 20 days (IQR 20.5) for controls. Looking to maternal blood exams, in the group of women treated with pravastatin, maximum transaminase, creatinine levels were lower than in controls, where the minimum platelet count was higher. Placenta examination did not reveal any significant differences in placental histopathological findings. No significant differences were observed in the investigated perinatal data, as well as in infant follow-up, although an increased prenatal weight gain was found in treated pregnancies in comparison to controls.Conclusions: Our data did not allow us to find significant differences in pregnancy outcome and infant follow-up, as well as in placental histological picture in preeclamptic patients

Botulinum toxin A (BoNT/A) is the first-line treatment for idiopathic cervical dystonia (ICD) and is widely used in the clinical setting. To date, scanty data are available on the effectiveness of BoNT in treating acquired cervical dystonia (ACD). Here we present a long-term follow-up of ACD patients treated with BoNT/A that focused on safety and efficacy. The study included subjects who had received at least six treatments of three commercially available BoNT/A drugs [abobotulinumtoxinA (A/Abo), incobotulinumtoxinA (A/Inco) and onabotulinumtoxinA (A/Ona)]. Safety and efficacy were assessed based on patients' self-reports regarding adverse effects (AE), duration of improvement of dystonia and/or pain relief. Global clinical improvement was measured on a six-point scale. 23 patients with ACD were administered 739 treatments (A/Abo in 235, A/Inco in 72, A/Ona in 432) with a mean number of treatments of 31 +/- 20 (range 6-76) and duration of 10 +/- 6 weeks (range 2-25). The mean dose was 737 +/- 292 U for A/Abo, 138 +/- 108 U for A/Inco and 158 +/- 80 U for A/Ona. The average benefit duration was 89 +/- 26 (A/Abo), 88 +/- 30 days (A/Inco), and 99 +/- 55 days (A/Ona) (p = 0.011); global clinical improvement for all sessions was 4 +/- 1. ANOVA one-way analysis indicated that A/Ona had the best profile in terms of duration (p < 0.05), whereas A/Abo had the best pain relief effect (p = 0.002). Side effects were reported in 9% of treatments (67/739), with ten treatments (1%) complicated by two side effects. Most side effects were rated mild to moderate; severe side effects occurred following three treatments with the three different BoNT; two required medical intervention. No allergic reactions were reported. Even after 25 years of repeated treatments, all serotypes of BoNT demonstrate positive effects in treating ACD with long-lasting efficacy and safety.

Botulinum toxin A (BoNT/A) is the first-line treatment for idiopathic cervical dystonia (ICD) and is widely used in the clinical setting. To date, scanty data are available on the effectiveness of BoNT in treating acquired cervical dystonia (ACD). Here we present a long-term follow-up of ACD patients treated with BoNT/A that focused on safety and efficacy. The study included subjects who had received at least six treatments of three commercially available BoNT/A drugs [abobotulinumtoxinA (A/Abo), incobotulinumtoxinA (A/Inco) and onabotulinumtoxinA (A/Ona)]. Safety and efficacy were assessed based on patients' self-reports regarding adverse effects (AE), duration of improvement of dystonia and/or pain relief. Global clinical improvement was measured on a six-point scale. 23 patients with ACD were administered 739 treatments (A/Abo in 235, A/Inco in 72, A/Ona in 432) with a mean number of treatments of 31 +/- 20 (range 6-76) and duration of 10 +/- 6 weeks (range 2-25). The mean dose was 737 +/- 292 U for A/Abo, 138 +/- 108 U for A/Inco and 158 +/- 80 U for A/Ona. The average benefit duration was 89 +/- 26 (A/Abo), 88 +/- 30 days (A/Inco), and 99 +/- 55 days (A/Ona) (p = 0.011); global clinical improvement for all sessions was 4 +/- 1. ANOVA one-way analysis indicated that A/Ona had the best profile in terms of duration (p < 0.05), whereas A/Abo had the best pain relief effect (p = 0.002). Side effects were reported in 9% of treatments (67/739), with ten treatments (1%) complicated by two side effects. Most side effects were rated mild to moderate; severe side effects occurred following three treatments with the three different BoNT; two required medical intervention. No allergic reactions were reported. Even after 25 years of repeated treatments, all serotypes of BoNT demonstrate positive effects in treating ACD with long-lasting efficacy and safety.

Simple Summary In this retrospective observational study, we evaluated data from patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NACT) in order to better define the impact of germline BRCA1/2 (gBRCA1/2) mutation status on outcomes in this patient population. Our results show that patients with BRCA1/2 mutation had a higher pathologic complete response (pCR) rate than non-mutated patients; nevertheless, the benefit was confirmed only in the subset of patients who received a platinum-based NACT. Furthermore, pCR was associated with improved Event Free Survival (EFS) and Overall Survival (OS), regardless of BRCA1/2 mutation status and type of NACT received. Long-term follow-up analyses are needed to further define the impact of gBRCA mutation status in patients with early-TNBC. Triple-negative breast cancer (TNBC) is characterized by earlier recurrence and shorter survival compared with other types of breast cancer. Moreover, approximately 15 to 25% of all TNBC patients harbor germline BRCA (gBRCA) 1/2 mutations, which confer a more aggressive phenotype. However, TNBC seems to be particularly sensitive to chemotherapy, the so-called 'triple negative paradox'. Therefore, Neoadjuvant chemotherapy (NACT) is currently considered the preferred approach for early-stage TNBC. BRCA status has also been studied as a predictive biomarker of response to platinum compounds. Although several randomized trials investigated the addition of carboplatin to standard NACT in early-stage TNBC, the role of BRCA status remains unclear. In this retrospective analysis, we evaluated data from 136 consecutive patients with Stage I-III TNBC who received standard NACT with or without the addition of carboplatin, in order to define clinical features and outcomes in BRCA 1/2 mutation carriers and non-carrier controls. Between January 2013 and February 2021, 67 (51.3%) out of 136 patients received a standard anthracyclines/taxane regimen and 69 (50.7%) patie

Objectives To investigate caregivers and patients characteristics related to different dimensions of burden in Parkinson's disease (PD). Methods 55 pairs of PD patients and caregivers were recruited. The burden was evaluated with the Caregiver Burden Inventory (CBI). Multivariate analysis was applied to evaluate the impact of caregivers' and patients' characteristics on the varying aspects of burden. Results ADL score was the dominant predictor for the total score and all dimensions of CBI, except for the social burden, which is strongly predicted by the motor severity of PD. As one can easily imagine, the Total CBI decreases as the ADL score increases. Discussion An increased appreciation for characteristics of caregiver burden is a fundamental aspect of the patient's global evaluation. Clinicians may need to directly probe for these factors in the caregiver as they may not be elicited routinely.

AIMS: To investigate predictors of the occurrence of subacute ventricular arrhythmias (VAs), defined as any VAs presenting after 48 h from admission in patients with Takotsubo Syndrome (TTS), and to evaluate the related in-hospital mortality.METHODS: This is a retrospective single-center study enrolling patients admitted between 2012 and 2017 with TTS according to International Takotsubo diagnostic criteria. Data collection included ECG on admission and at 48 h, telemetry monitoring and transthoracic echocardiogram.RESULTS: We enrolled 93 patients; during in-hospital stay (mean 14 ± 16 days) subacute VAs occurred in 25% of patients (VAs group). Life-threatening VAs occurred in 6% of patients (3 sustained ventricular tachycardia, 1 torsade de pointes, 1 ventricular fibrillation) and not life-threatening VAs in 19% (6 non-sustained ventricular tachycardia and 12 premature ventricular contractions > 2000 in 24 h). Mortality was higher in the VAs than in the non-VAs group (P = 0.03), without differences in terms of life-threatening and not life-threatening subacute VAs (P = 0.65) and VAs on admission (P = 0.25). Logistic regression identified the following independent predictors of subacute VAs occurrence: VAs on admission {odds ratio [OR] 22.5 (3.9-131.8), P = 0.001]}, New York Heart Association (NYHA) class III-IV on admission [OR 6.7 (1.3- 34.0), P = 0.021] and QTc at 48 h [OR 1.01 (1.00-1.03), P = 0.046].CONCLUSION: TTS patients with VAs and NYHA class III-IV on admission and higher QTc at 48 h are at increased risk of subacute VAs occurrence, associated with higher in-hospital mortality. Awareness of this potential complication is critical for proper patients management.

Post-dialysis fatigue and survival in patients on chronic hemodyalisi

Objective:Neurological sequelae of SARS-CoV-2 infection have already been reported, but there is insufficient data about the impact of the pandemic on the management of the patients with chronic neurological diseases. We aim to analyze the effect of COVID-19 pandemic and social restriction rules on these fragile patients. Methods:Patients with chronic neurologic diseases routinely followed at the outpatient clinic of Gemelli University Hospital, Rome, were assessed for symptoms suggestive of SARS-CoV-2 infection in the pandemic period, consequences of social restrictions, and neurological disease features, concomitant medical conditions, current medical and disease-specific treatments. Data source: a dedicated telephone survey designed to encompass questions on COVID-19 symptoms and on pandemic effects in chronic neurologic conditions. Results:Overall, 2,167 individuals were analyzed: 63 patients reported contact with COVID-19 positive cases, 41 performed the swab, and 2 symptomatic patients tested positive for COVID-19 (0.09%). One hundred fifty-eight individuals (7%) needed urgent neurological care, deferred due to the pandemic; 641 patients (30%) suspended hospital treatments, physiotherapy or other support interventions; 405 individuals (19%) reported a subjective worsening of neurological symptoms. Conclusions:In our population, the presence of neurological chronic diseases did not increase the prevalence of COVID-19 infection. Nevertheless, the burden of neurological disorders has been worsened by the lockdown.

Background Safinamide, as a levodopa adjunct, is effective in reducing motor fluctuations in Parkinson's disease (PD) patients; however, scarce evidence is available regarding its use in older PD patients. Aim To evaluate the safety and tolerability of safinamide as an adjunct therapy in patients aged >= 60 years with advanced PD. Methods A retrospective study including 203 PD patients admitted to a geriatric day hospital, who were evaluated following an extensive clinical protocol. Safinamide use was categorized as never used, ongoing, and withdrawn. Potential correlations of Safinamide withdrawal were investigated in stepwise backward logistic regression models. Results A total of 44 out of 203 participants were current or former users of Safinamide. Overall, 14 (32%) patients discontinued due to treatment-emergent adverse events (TEAEs). Withdrawal was not associated with older age. Conclusions Safinamide as an adjunct therapy in patients aged >= 60 years with advanced PD was found to be safe and well-tolerated in older patients. There were no specific demographic or clinical characteristics associated with suspension.

Background: Pain is a core symptom of hidradenitis suppurativa (HS) and is of complex, multifactorial origin. HS patients frequently report typical neuropathic pain qualities, but its prevalence has been poorly described. Methods: In this cross-sectional study, we examine the prevalence of neuropathic pain (NP) component and related pain-characteristics of a hospital-based cohort of patients with symptomatic HS. We administered the pain-DETECT tool (PDQ), a validated screening tool for NP, collecting clinical and patient-reported data on pain, pruritus and pain-management. We obtained 110 complete datasets from symptomatic HS patients (49.1% females; Hurley I (27.3%])-II (45.5%)-III (27.3%)). According to the PDQ tool, 30% of patients were classified with a high probability (>90%) of neuropathic pain (LNP). LNP status was significantly associated with increased pain severity, disease activity, pruritus intensity and use of pain medication. Regression analysis showed a significant impact of the PDQ score on patient-reported outcomes, including pain severity and the dimensions of activity and affective pain interference. HS patients may present a mixed chronic pain phenotype with a neuropathic component, thus requiring additional pain-assessments. A multi-modal approach to pain management, in combination with disease-specific treatment, should be implemented in future interventional studies.

Recently, it has been demonstrated that chronic inflammation could have a role on fatigue onset in chronic hemodialysis (HD). Research on neuro-immune interactions highlighted that an alteration of basal ganglia functioning, secondary to chronic inflammation, may translate in a reduced motivation and altered reward processes in chronic diseases. This study investigated a possible correlation between fatigue severity and reward mechanisms, that regulate motivational dispositions, in HD patients. Evaluation scales were administered to ninety-four patients on HD (54 Male, 40 Female; Mdage = 67±26.5; Dialytic Mdage in years = 4±6.3. Fatigue was assessed by using Fatigue Severity Scale (FSS). Behavioural Inhibition System (BIS) and Behavioural Activation System (BAS) Scale was administered to investigate approach/avoidance behaviours. Anxiety and depression were measured by State-Trait Anxiety Inventory (STAI-Y) and Beck Depression Inventory (BDI-II). Results show that the distribution of HD patients for FSS score did not show a normal pattern. FSS score was significantly higher in patients with high BIS Z-score than in patients with low and medium BIS Z-score. BDI score and STAI-Y scores were similar among BIS Z-score groups of patients. Findings suggest that in patients on chronic hemodialysis there is a correlation between fatigue severity symptoms and motivational disposition mechanisms that predispose to action inhibition.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) with second-generation contrast agents performed 1-month after HCC treatment is almost as sensitive as contrast-enhanced computed tomography (CECT) in depicting the residual tumor. However, the efficacy of CEUS performed early after the procedure is still debated. AIM: We evaluated the diagnostic accuracy of CEUS for the assessment of tumour response shortly after locoregional therapy in patients with unresectable HCC. METHODS: Ninety-four patients with 104 HCC lesions who were scheduled to receive PEI, RFA, TACE or combined treatment were enrolled in this study. With CECT at 1-month as the reference standard, the diagnostic accuracy of CEUS performed 48-hours after the procedure was evaluated. Patients were followed-up to look for tumor or disease progression. RESULTS: Based on CECT findings, 43/104 lesions were diagnosed as having residual viability after 1 month. CEUS performed 48-hours after treatment detected residual tumor in 34/43 nodules with treatment failure at CECT with a sensitivity, specificity, PPV, NPV and accuracy of 79.1%, 96.7%, 94.4%, 86.8% and 89% respectively. There was a high degree of concordance between CEUS and CECT (kappa coefficient=0.78). An hyperemic halo was detectable in 35 lesions without a statistically significant difference between concordant and discordant cases. In patients with uninodular disease responders according to 48 hours CEUS had a significantly longer mean overall survival and time to progression compared to non-responders. CONCLUSION: CEUS performed 48 hours after treatment can be considered a reliable modality for the evaluation of the real extent of necrosis and has prognostic value in the assessment of hepatocellular carcinoma.

Background: Single-center trials demonstrated moderate-substantial level of interobserver agreement in the evaluation of ultrasound (US) features of thyroid nodules. Multicenter studies on US agreement, however, are scanty, and data on intraobserver agreement are poor. Aim of the study was to assess inter- and intraobserver agreement between different thyroid centers and different specialists. Methods: A blinded analysis of 100 electronically recorded thyroid nodule US images was conducted in three large-volume thyroid centers by seven radiologists and endocrinologists. The evaluation was repeated after randomization 4 months later. The following US characteristics were evaluated: composition, echogenicity, margins, intranodular echogenic spots, vascularity, and shape. Thyroid nodules were also classified according to AACE/ACE/AME, EU-TIRADS, ATA, and ACR-TIRADS US classifications. Intra- and interobserver agreement was calculated using cross-tabulation expressed as mean Cohen's Kappa. Results: Interobserver agreement for US features: K-coefficient was 0.53 for composition, 0.47 for echogenicity, 0.46 for intranodular vascularity, and 0.33 for margins of the nodules. For echogenic foci, the K-coefficient was 0.47 for microcalcifications, 0.38 for macrocalcifications, 0.11 for the subcategory comet-tail artifacts, and 0.42 for shape. Operators resulted uncertain on hyperechoic foci definition in 16% of cases and described them as "hyperechoic foci of uncertain significance." Interobserver Cohen-K for US classification systems was 0.44 for AACE, 0.42 for ACR-TIRADS, 0.39 EU-TIRADS, and 0.34 for ATA. Intraobserver agreement: the K-coefficient for nodule US features was 0.62 for intranodular vascularity, 0.58 for composition, 0.60 for echogenicity, 0.54 for macrocalcifications, 0.55 for microcalcifications, 0.47 for comet tails, 0.39 for margins, and 0.35 for shape. Intraobserver Cohen-K for US classification systems was 0.54 for AACE, 0.49 for ACR-TIRADS, 0.38

Classification of the category of diabetes is extremely important for clinicians to diagnose and select the correct treatment plan. Glycosylation, oxidation and other post-translational modifications of membrane and transmembrane proteins, as well as impairment in cholesterol homeostasis, can alter lipid density, packing, and interactions of Red blood cells (RBC) plasma membranes in type 1 and type 2 diabetes, thus varying their membrane micropolarity. This can be estimated, at a submicrometric scale, by determining the membrane relative permittivity, which is the factor by which the electric field between the charges is decreased relative to vacuum. Here, we employed a membrane micropolarity sensitive probe to monitor variations in red blood cells of healthy subjects (n=16) and patients affected by type 1 (T1DM, n=10) and type 2 diabetes mellitus (T2DM, n=24) to provide a cost-effective and supplementary indicator for diabetes classification. We find a less polar membrane microenvironment in T2DM patients, and a more polar membrane microenvironment in T1DM patients compared to control healthy patients. The differences in micropolarity are statistically significant among the three groups (p<0.01). The role of serum cholesterol pool in determining these differences was investigated, and other factors potentially altering the response of the probe were considered in view of developing a clinical assay based on RBC membrane micropolarity. These preliminary data pave the way for the development of an innovative assay which could become a tool for diagnosis and progression monitoring of type 1 and type 2 diabetes.

INTRODUCTION: Immunosuppressive treatment of patients with idiopathic membranous nephropathy (IMN) is debated due to its possible side effects. The 2012 KDIGO guidelines suggest alkylating agents as first choice therapy. The aim of the study is to retrospectively evaluate the induction and maintenance of clinical remission in patients with histological diagnosis of IMN undergoing steroid and/or cyclosporine therapy at the Nephrology Unit of the Sant'Andrea Hospital in Rome. MATERIALS AND METHODS: Therapy A (conservative) was reserved to low-risk patients. 8 medium and high risk patients were induced by Therapy B (Prednisone 1 mg / kg ≤12-16 weeks plus 8 weeks withdrawal); 6 patients by Therapy C (Prednisone 1 mg /kg ≥20-24 weeks plus 8 week withdrawal) and, finally, 6 steroid-resistent patients by Therapy D (steroid withdrawal + cyclosporine 3-5 mg / kg for 2 years). RESULTS: Complete remission was observed in 37.5% of patients in Therapy B, in 83.3% of patients in Therapy C and in 66.6% of patients in Therapy D. Patients in group B relapsed more frequently than patients in the other groups. Side effects were irrelevant. CONCLUSIONS: In view of the potential cytotoxicity of alkylating agents, steroids are a valid alternative in inducing and maintaining clinical remission over time, when administered with a more aggressive induction scheme. In cases of steroid resistance or rapid relapse, cyclosporine is a valid alternative to alkylating agents.

Background: This systematic review with meta-analysis was carried out to study the relationship between workplace violence and sleep problems. Methods: The PRISMA statement was used to conduct a systematic search of the literature on PubMed/MEDLINE, Scopus, Sociological abstract, DOAJ, Web of Science, and Google Scholar databases. Of the original number of 749 studies, 34 were included in the systematic review, and 7 in the meta-analysis. Results: A total of 119,361 participants from 15 different countries took part in these studies which were published between 1999 and 2019. Significant heterogeneity was observed among the studies (I 2 = 96%). In a random-effects meta-analysis model, pooled odds ratio (OR) analysis revealed that there was a direct relationship between occupational exposure to violence and sleep problems (OR = 2.55; 95% CI = 1.77– 3.66). According to the GRADE guidelines, the quality of evidence of the association was low. Conclusions: The findings of this study demonstrate that occupational exposure to physical, verbal, or sexual violence is associated with sleep problems. Further research on the relationship between violence and sleep is needed so that appropriate measures can be taken to prevent violence and improve sleep hygiene in the workplace.

Background Recombinant (rec-) coagulation factor VIII concentrates available for hemophilia A (HA) treatment differ in cell line production and structure, which could affect their pharmacodynamics and immunogenicity. Clinical trials showed that previously untreated patients with severe HA present higher rates of inhibitor development if treated with rec-FVIII products and that differences do exist as to inhibitor's formation among different rec-FVIII products. This finding could arise from several causes, such as absence of von Willebrand factor, different glycosylation profiles, or processes of molecular aggregation of the recombinant FVIII molecules. Objectives/Methods In this study, using size exclusion high-performance liquid chromatography (SE-HPLC), dynamic light scattering (DLS) spectroscopy, and functional biochemical assays, we investigated the purity grade, FX activating ability, and aggregation status of three recombinant marketed products (Advate [Baxalta], Refacto AF [Pfizer], and Kogenate [Bayer]). Results The overall analysis of the results obtained with SE-HPLC and DLS spectroscopy showed that the three recombinant FVIII concentrates contain low but significant amounts of molecular aggregates. This phenomenon was less evident for the Advate product. Molecular aggregation negatively affects the in vitro pharmacodynamics of the concentrates with higher aggregates' content. Conclusions This study shows that the three pharmaceutical formulations of recombinant FVIII contain variable amounts of molecular aggregates after their reconstitution at therapeutic concentrations. This phenomenon negatively affects the in vitro potency of the products with higher aggregates' content and might be invoked as a contributing cause of their increased risk to induce the formation of FVIII inhibitors.

Background Recombinant (rec-) coagulation factor VIII concentrates available for hemophilia A (HA) treatment differ in cell line production and structure, which could affect their pharmacodynamics and immunogenicity. Clinical trials showed that previously untreated patients with severe HA present higher rates of inhibitor development if treated with rec-FVIII products and that differences do exist as to inhibitor's formation among different rec-FVIII products. This finding could arise from several causes, such as absence of von Willebrand factor, different glycosylation profiles, or processes of molecular aggregation of the recombinant FVIII molecules. Objectives/Methods In this study, using size exclusion high-performance liquid chromatography (SE-HPLC), dynamic light scattering (DLS) spectroscopy, and functional biochemical assays, we investigated the purity grade, FX activating ability, and aggregation status of three recombinant marketed products (Advate [Baxalta], Refacto AF [Pfizer], and Kogenate [Bayer]). Results The overall analysis of the results obtained with SE-HPLC and DLS spectroscopy showed that the three recombinant FVIII concentrates contain low but significant amounts of molecular aggregates. This phenomenon was less evident for the Advate product. Molecular aggregation negatively affects the in vitro pharmacodynamics of the concentrates with higher aggregates' content. Conclusions This study shows that the three pharmaceutical formulations of recombinant FVIII contain variable amounts of molecular aggregates after their reconstitution at therapeutic concentrations. This phenomenon negatively affects the in vitro potency of the products with higher aggregates' content and might be invoked as a contributing cause of their increased risk to induce the formation of FVIII inhibitors.

Purpose: The symptom burden of fatigued hemodialysis patients is poorly known. We aimed to investigate possible differences in the prevalence and severity of symptoms between fatigued and not fatigued patients on chronic hemodialysis. Methods: All prevalent patients on chronic hemodialysis referring to the Hemodialysis Service between January 2016 and June 2017 were considered eligible. The Dialysis Symptom Index (DSI) questionnaire was performed during the dialysis treatment. Patients underwent assessment of fatigue using the Italian version of the vitality scale of the SF-36 (SF-36VS). Results: We studied 137 patients: 107 (78.1%) were fatigued and 30 (31.9%) were non-fatigued. The median [95% CI] number of symptoms was 15 [14–16] for patients who reported fatigue and 9 [8–19] for the non-fatigued (P < 0.0001). In fatigued patients, with respect to non-fatigued ones, the prevalence of dry skin, itching, muscle soreness, bone or joint pain, restless legs, shortness of breath, feeling sad, feeling anxious, difficulty concentrating, and difficulty becoming sex aroused was significantly higher. Restless legs, feeling sad, difficulty concentrating, and difficulty becoming sex aroused were symptoms independently associated with fatigue. The severity of dry skin, trouble staying asleep, and bone/joint pain was higher in fatigued patients. Conclusion: Fatigued hemodialysis patients report suffering from physical and emotional symptoms more frequently than non-fatigued patients. This finding suggests the need to accurately and routinely define the symptom burden of chronic hemodialysis patients and may help to investigate eventually common underlying pathogenic mechanisms of symptoms in these patients.

Background: In liver cirrhosis, the renin-angiotensin-aldosterone system is involved in the pathogenesis of portal hypertension. Its effector, angiotensin II, is generated by angiotensin-converting enzyme (ACE). Serum ACE levels are affected by I/D polymorphism of its gene, with alleles I and D being associated, respectively, with lesser and greater activity of the enzyme. In cirrhotic patients carrying the ACE I allele, an increased risk for gastro-oesophageal varices was observed. Aim: The aim of our study was to evaluate whether ACE I/D polymorphism influenced portal pressure. Methods: Fifty-one consecutive cirrhotic patients were divided based on ACE genotype (DD, ID, and II). Kidney and liver function tests, upper endoscopy, and hepatic venous pressure gradient measurement (HVPG) were performed in all patients. Results: The presence of the ACE I allele was associated with a higher HVPG value (18.7 ± 6.4 vs 10.3 ± 6.3 mmHg; P < .001), higher frequency of large gastrooesophageal varices (59.3% vs 25.0%; P < .05), and higher frequency of variceal bleeding (63.0% vs 29.2%; P < .05). No significant differences were found between patients with and those without the ACE I allele regarding Child-Pugh score, MELD score, ascites, and hepatic encephalopathy. Conclusion: ACE I/D polymorphism seems to influence the severity of portal hypertension and the risk of variceal bleeding in liver cirrhosis, regardless of the severity of liver disease.

Purpose: The symptom burden of fatigued hemodialysis patients is poorly known. We aimed to investigate possible differences in the prevalence and severity of symptoms between fatigued and not fatigued patients on chronic hemodialysis. Methods: All prevalent patients on chronic hemodialysis referring to the Hemodialysis Service between January 2016 and June 2017 were considered eligible. The Dialysis Symptom Index (DSI) questionnaire was performed during the dialysis treatment. Patients underwent assessment of fatigue using the Italian version of the vitality scale of the SF-36 (SF-36VS). Results: We studied 137 patients: 107 (78.1%) were fatigued and 30 (31.9%) were non-fatigued. The median [95% CI] number of symptoms was 15 [14–16] for patients who reported fatigue and 9 [8–19] for the non-fatigued (P < 0.0001). In fatigued patients, with respect to non-fatigued ones, the prevalence of dry skin, itching, muscle soreness, bone or joint pain, restless legs, shortness of breath, feeling sad, feeling anxious, difficulty concentrating, and difficulty becoming sex aroused was significantly higher. Restless legs, feeling sad, difficulty concentrating, and difficulty becoming sex aroused were symptoms independently associated with fatigue. The severity of dry skin, trouble staying asleep, and bone/joint pain was higher in fatigued patients. Conclusion: Fatigued hemodialysis patients report suffering from physical and emotional symptoms more frequently than non-fatigued patients. This finding suggests the need to accurately and routinely define the symptom burden of chronic hemodialysis patients and may help to investigate eventually common underlying pathogenic mechanisms of symptoms in these patients.

Context British Thyroid Association (BTA), American Thyroid Association (ATA), and American Association of Clinical Endocrinologists (AACE/ACE/AME) recommend for thyroid nodules an ultrasound (US)-based stratification of risk of malignancy. Aim of our study was to assess the diagnostic accuracy of US classification systems and their reliability for indication to fine-needle aspiration (FNA). Design Prospective study on 987 thyroid nodules consecutively referred for FNA. US images were independently reviewed by four experts for assignment of malignancy risk. Cytologically benign nodules had confirmation with a second FNA, whereas Bethesda class IV, V, and VI nodules were operated upon. Class III nodules had surgery or follow-up on the basis of clinical, immunocytochemical, and US features. Results BTA: Malignancy rate was 2.8% in benign, 10.0% in indeterminate, 51.3% in suspicion, and 80.9% in malignant US class. Sensitivity was 0.74, specificity was 0.92, and accuracy was 0.89. ATA: Malignancy rate was 0.0% in benign, 2.2% in very low suspicion, 3.0% in low suspicion, 5.8% in intermediate, and 55.0% in high suspicion US class. Sensitivity was 0.81, specificity was 0.87, and accuracy was 0.86. AACE/ACE/AME: Malignancy rate was 1.1% in low-risk, 4.4% in intermediate-risk, and 54.9% in high-risk US class. Sensitivity was 0.82, specificity was 0.87, and accuracy was 0.86. K correlation coefficient was 78.9%, 76.9%, and 82.0% for BTA, ATA, and AACE/ACE/AME classifications. Conclusions Classification systems had elevated predictive value of malignancy in high-risk classes. ATA and AACE/ACE/AME systems were effective for ruling out indication to FNA in low-US-risk nodules. A similar diagnostic accuracy and a substantial interobserver agreement was provided by the three- and the five-category classifications.

Ferritin self-assembly has been widely exploited for the synthesis of a variety of nanoparticles for drug-delivery and diagnostic applications. However, despite the crucial role of ferritin self-assembly mechanism for probes encapsulation, little is known about the principles behind the oligomerization mechanism. In the present work, the novel “humanized” chimeric Archaeal ferritin HumAfFt, displaying the transferrin receptor-1 (TfR1) recognition motif typical of human H homopolymer and the unique salt-triggered oligomerization properties of Archaeoglobus fulgidus ferritin (AfFt), was site-selectively labeled with N-(1-pyrenyl)maleimide on a topologically selected cysteine residue inside the protein cavity, next to the dimer interface. Pyrene characteristic fluorescence features were exploited to investigate the transition from a dimeric to a cage-like 24-meric state and to visualize the protein in vitro by two photon fluorescence microscopy. Indeed, pyrene fluorescence changes upon ferritin self-assembly allowed to establish, for the first time, the kinetic and thermodynamic details of the archaeal ferritins oligomerization mechanism. In particular, the magnesium induced oligomerization proved to be faster than the monovalent cation-triggered process, highly cooperative, complete at low MgCl2 concentrations, and reversed by treatment with EDTA. Moreover, pyrene intense excimer fluorescence was successfully visualized in vitro by two photon fluorescence microscopy as pyrene-labeled HumAfFt was actively uptaken into HeLa cells by human transferrin receptor TfR1 recognition, thus representing a unique nano-device building block for two photon fluorescence cell imaging.

OBJECTIVE: Intrauterine growth curves are considered an essential instrument in prenatal medicine for an appropriate auxological classification of foetuses and they have a great importance in clinical practice. Nowadays, in Italy a national curve published in 1975, is the most used. It's based on birth weights of 8458 newborns from physiological pregnancies. The aim of the present study is to develop a modern foetal growth curve based on accurately selection of 35 240 physiological singleton Italian pregnancies with sure gestational age confirmed by ultrasound. METHODS: This is a retrospective analysis of 35 240 pregnancies from "A. Gemelli" University Hospital in Rome and "S. Anna" University Hospital in Turin from January 2001 to December 2006. Non-resident pregnant women or coming from other countries, women with diabetes, hypertensive disorders of pregnancy, multiple pregnancies, foetuses with major malformations and /or chromosomal disorders and stillborn foetuses were excluded. RESULTS: An increasing trend of median neonatal weight, in comparison that with the previous Italian National Curve drawn up in 1975, was found. CONCLUSIONS: Combining data from two centres, a new foetal growth curve, in which the 10th and the 90th percentiles are clinically reliable, was performed, in order to have a better tool to evaluate the Italian foetal population. A trend towards an increase of birth weight was observed if compared to previous growth curve drawn up more than 30 years ago.

BACKGROUND: Intrauterine growth curves are considered an essential instrument in prenatal medicine for an appropriate auxological classification of fetuses and they have a great importance in clinical practice. Nowadays, in Italy a national curve published in 1975, is the most used. It Is based on birth weights of 8458 newborns from physiological pregnancies. The aim of the present study was to develop a modern fetal growth curve based on accurately selection of 35 240 physiological singleton Italian pregnancies with sure gestational age confirmed by ultrasound. METHODS: This is a retrospective analysis of 35,240 pregnancies from "A. Gemelli" University Hospital in Rome and "S. Anna" University Hospital in Turin from January 2001 to December 2006. Non-resident pregnant women or coming from other countries, women with diabetes, hypertensive disorders of pregnancy, multiple pregnancies, fetuses with major malformations and/or chromosomal disorders and stillborn fetuses were excluded. RESULTS: An increasing trend of median neonatal weight, in comparison with the previous Italian National Curve drawn up in 1975, was found. CONCLUSIONS: Combining data from two centers, a new fetal growth curve, in which the 10th and the 90th percentiles are clinically reliable, was performed, in order to have a better tool to evaluate the Italian fetal population. A trend towards an increase of birth weight was observed if compared to previous growth curve drawn up more than 30 years ago.

AIMS: Little is known about postdialysis fatigue (PDF), a debilitating symptom of hemodialysis patients. METHODS: In 5 hemodialysis units of northern-centre Italy, patients were regarded to suffer from PDF if they spontaneously offered this complaint when asked the open-ended question: Do you feel better or worse after dialysis? If worse, please specify in which way. A complaint of fatigue would be probed further with questions directed at its duration, frequency and intensity, allowing creation of a fatigue index of severity (one third of the sum of these three parameters, each rated from 1 to 5). Patients were stratified into three groups according the severity of PDF: 1) score = 0; 2) score = 1-3; 3) score > 3. RESULTS: We studied 271 patients: 164 had PDF and 107 had not. PDF patients had significantly longer time of recovery after dialysis (TIRD). TIRD was significantly associated with PDF duration, intensity, and frequency. Patients with PDF were older and had a lower ADL score. At multivariate analysis, PDF was significantly associated with TIRD. In multivariate model that did not include TIRD, PDF was independently associated with age and ADL. Sixty patients had moderate PDF and 104 severe PDF. In patients with severe PDF, age and dialytic age were higher, ADL and IADL scores were lower, TIRD was longer and the ultrafiltration rate was lower. At multivariate analysis, PDF severity was independently associated with TIRD. In the model without TIRD, PDF severity was associated with ADL only. CONCLUSION: PDF is frequent and associated with age and ADL. Dialytic variables seem unrelated to PDF.

Purpose: To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules. Materials and methods: Institutional review board approval was obtained, and patients’ consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 57 ± 14 years) with LA and 152 (107 females, age 57 ± 14 years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12 months and complications were evaluated. Results: No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12 months was −67 ± 19% vs. −57 ± 21% (p < 0.001) − 70 ± 19% vs. −62 ± 22% (p = 0.001) in LA group and in RFA group, respectively. Nodules with volume >30 mL had significantly higher percentage volume reduction at 6 and 12 months (−69 ± 19 vs. −50 ± 21, p = 0.001) and (−73 ± 18 vs. −54 ± 23 8, p = 0.001) in the LA group than in the RFA group, respectively. In both groups, operator’s skills affected the results. Major complications occurred in 4 cases in each group (p = 0.116) Conclusions: LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator’s skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique.

Spinal anesthesia (SA) in the lateral decubitus position is often used to perform total hip arthroplasty (THA). Hypobaric local anesthetic ensures enhanced and prolonged sensory and motor block in the involved side. The aim of this study was to compare the intraoperative anesthetic efficacy of hypobaric with isobaric levobupivacaine solutions for THA.

Botulinum toxin is considered as first-line therapy for cervical dystonia, but few papers have addressed these issues in the long term. Aim of this study was to investigate the long-term efficacy and safety of abobotulinumtoxin A (A/Abo) in patients with primary cervical dystonia. Consecutive patients who received at least six injections with A/Abo were included. Safety was assessed on patients' self-reports. Efficacy was assessed by recording the total duration of benefit, duration of maximum efficacy, disease severity measured by means of the Tsui score, and pain intensity evaluated by means of the visual analog scale (VAS). Thirty-nine patients with PCD were included. The mean dose injected was 701.5 ± 280.6 U. The mean duration of the clinical improvement was 93.0 ± 30.7 days, while the mean duration of the maximum clinical improvement was 77.1 ± 27.1 days. The mean VAS before and 4 weeks after injection was 4.4 ± 1.8 and 1.8 ± 1.6, respectively. The mean Tsui score before and 4 weeks after treatment was 5.7 ± 1.8 and 3.5 ± 1.5, respectively. Doses of A/Abo and duration of the maximum clinical improvement significantly increased over time, while the Tsui score and VAS displayed a tendency to decrease along time. Side effects occurred in 19.6% of all the treatments but were severe in only four injections. The results of our study confirm the effectiveness and safety profile of A/Abo for the long-term treatment of primary cervical dystonia.

Purpose To evaluate the diagnostic accuracy of shear-wave elastography (SWE) in identifying different degrees of fibrosis in a cohort of consecutive children and adolescents with nonalcoholic steatohepatitis (NASH). Materials and Methods Consecutive pediatric patients scheduled to undergo liver biopsy were studied with an ultrasonography-based SWE system. Elastography was performed in 68 of 69 patients with biopsy-proved NASH (37 boys and 31 girls; mean age, 12.6 years ± 2.48; age range, 8-17 years). The correlations among laboratory findings, liver stiffness, and fibrosis score were analyzed, and the area under the receiver operating characteristic curve (AUC) was used to assess the presence of any fibrosis (score ≥F1) or significant fibrosis (score ≥F2). Findings from histologic examination were used as the standard of reference. Results SWE showed a very high correlation with liver fibrosis (P < .001) at univariate and multivariate analyses. The AUCs for the association of any and significant fibrosis were 0.92 (95% confidence interval [CI]: 0.86, 0.98) and 0.97 (95% CI: 0.95, 0.99), respectively. The intraclass correlation coefficient for absolute agreement was 0.95 (95% CI: 0.90, 0.97). Conclusion SWE is an accurate and reproducible noninvasive technique that efficiently depicts the presence of significant liver fibrosis and, less accurately, mild liver fibrosis in pediatric patients with nonalcoholic fatty liver disease. Larger clinical prospective studies are warranted to confirm SWE accuracy and establish threshold values for fibrosis grading in comparison or in combination with other noninvasive methods. © RSNA, 2016

AIMS: Charcot Neuroarthropathy (CN) is a disabling complication, culminating in bone destruction and involving joints and articular cartilage with high inflammatory environment. Its real pathogenesis is unknown yet. In autoinflammatory diseases, as rheumatoid arthritis, characterized by inflammation and joints involvement, autoantibodies against post-translationally modified (ox-PTM) collagen type I (CI) and Type II (CII) were detected. Therefore, the aim of our study was to assess the potential involvement of autoimmunity in CN, investigating the presence of autoantibodies ox-PTM-CI and -CII, in subjects with CN. METHODS: In this case-control study, we enrolled 124 subjects with type 2 diabetes mellitus (47 with CN, 37 with diabetic peripheral neuropathy without CN, and 40 withuncomplicated diabetes), and 32 healthy controls. CI and CII were modified with ribose and other oxidant species and the modifications were evaluated with SDS-PAGE. Binding of sera from the subjects were analyzed with ELISA. RESULTS: Age, body mass index, waist and hip circumferences, and lipid profile were similar across the four groups, as well as glycated hemoglobin and duration of diabetes among people with diabetes. An increased binding to both native and all oxidative-modified forms of CII was found in subjects with CN and DN. Conversely, for CI, an aspecific increased reactivity was noted. CONCLUSIONS: Our results detected the presence of autoantibodies against oxidative posttranslational modified collagen, particularly CII, in subjects with CN and DN, suggesting the possible involvement of autoimmunity. Further studies are required to understand the role of autoimmunity in the pathogenesis of CN.

Human chitotriosidase (Chit) increases during the osteoclast differentiation and their activity. We demonstrated that serum Chit was significantly higher in osteoporotic subjects than in healthy control ones and revealed a negative correlation between Chit and bone mineral density (BMD). This is the first study showing a correlation between Chit and severe postmenopausal osteoporosis.

Data on the outcome of chronic kidney disease (CKD) patients who are hospitalized and start unplanned urgent haemodialysis (HD) are lacking. This prospective, longitudinal, observational study aimed to define the hospital mortality rate and associated factors in CKD patients who start unplanned urgent HD.

Background: This study aims to evaluate, in patients on chronic hemodialysis (PHD), the levels of endotoxin through a chemiluminescent bioassay based on the oxidative burst reaction of activated neutrophils to complement coated LPS-IgM immune complexes and define the variables possibly correlated. Methods: In 61 PHD, we measured serum endotoxin activity (EA) with the Endotoxin Activity Assay (EAATM) and we defined the possible association with demographic, clinical and laboratory variables. Results: Mean serum EA was 0.43 ± 0.26 UI. EA was low (<0.40) in 29 patients (47.5%), intermediate (0.40-0.60) in 14 (23%) and high (>0.60) in 18 (29.5%). A significant exponential relationship was detected between EA and serum interleukin-6 (IL-6) levels (r = 0.871). At the multiple regression analysis, intermediate-high EA was directly associated only with serum IL-6 levels. In a second model of multiple regression analysis without the variable serum IL-6 levels, intermediate-high EA was directly associated with constipation and serum troponin levels and inversely associated with serum albumin and the monthly number of sevelamer tablets. Conclusions: A high percentage of PHD has intermediate or high EA. Intermediate-high EA is significantly associated with serum IL-6 levels.

Objectives: A systematic review was conducted to assess the effectiveness of MRI in evaluating upper airway structures in children affected by obstructive sleep apnoea syndrome (OSAS). Methods: A literature search was performed in the Cochrane Central Register of Controlled Trials, Web of Science, Scopus and PubMed databases from their inception to 31/03/2016, including available randomized controlled trials and controlled clinical trials published in English assessing the use of MRI integrated with traditional polysomnography (PSG) among children up to 15 years of age affected by OSAS. The primary outcome to be evaluated was the efficacy of MRI in analyzing the upper airway total volume among healthy children compared with children affected by OSAS. Secondary outcomes were to compare the efficacy of MRI in analyzing the upper airway cross-sectional area in the areas adjacent to the adenoids and tonsils, adenoid and tonsil volume, and soft-tissue and maxillofacial bone parameters in the same sample. Results were expressed using a random-effects model and mean differences (MD) with 95% confidence intervals (CI). Results: The search yielded 1005 titles in total; the selection process narrowed to 3 titles, which were all assessed as indicating an unclear level of risk of bias. The meta-analysis found evidence of MRI effectiveness in evaluating differences in the upper airway total volume between paediatric patients affected by OSAS and paediatric patients not affected by OSAS (MD 20.56 cm3; 95% CI: 21.05 to 20.07). Conclusions: Although MRI could be considered effective in evaluating upper airway structures in children affected by OSAS, based on the present evidence, PSG is still the golden standard and further studies are required to verify MRI reliability.

Background There is uncertainty about the optimal method for measuring the decompressive craniectomy (DC) surface area and how large the DC should be. Methods A radiological technique for measuring the surface area of removed bone flaps in a series of 73 DCs was developed. Preoperative and early postoperative computed tomography scans of each patient were evaluated. Midline shift (MLS) was considered the key factor for successful DC and was assigned to either normal (0–4 mm) or pathological (≥5 mm) ranges. The association between postoperative MLS and patient survival at 12 months was assessed. Results Measurements of all removed bone flaps yielded a mean surface area of 7759 mm2. The surface area of the removed bone flap did not influence survival (surviving 7643 mm2 vs. deceased 7372 mm2). The only factor associated with survival was reduced postoperative MLS (P < 0.034). Risk of death was 14.4 (3.0–70.1)-fold greater in patients with postoperative shift ≥5 mm (P < 0.001). Conclusion The ideal surface area for “large” square bone flaps should result in an MLS of <5 mm. Enlargement of the craniectomy edges should be considered for patients in whom MLS ≥5 mm persists according to early postoperative computed tomography scans.

The usefulness, the methods and the criteria of intra-operative monitoring of the parathyroid hormone (ioPTH) during parathyroidectomy (PTX) for renal secondary hyperparathyroidism (rSHPT) in patients on chronic hemodialysis remain still matter of debate. The present study aimed to evaluate the ability of a low cost central-laboratory second generation PTH assay to predict an incomplete resection of parathyroid glands (PTG). METHODS: The ioPTH decay was determined In 42 consecutive patients undergoing PTX (15 subtotal and 27 total without auto-transplant of PTG) for rSHPT. The ioPTH monitoring included five samples: pre-intubation, post-manipulation of PTG and at 10, 20 and 30min post-PTG excision. The patients with PTH exceeding the normal value (65pg/ml) at the first postoperative week, 6 and 12months were classified as persistent rSHPT. RESULTS: The concentrations of ioPTH declined significantly over time in patients who received total or subtotal PTX; however, no difference was found between the two types of PTX. Irrespective of the type of PTX and the number of PTG removed, combining the absolute and percentage of ioPTH decay at 30min after PTG excision, we found high sensitivity (100%), specificity (92%), negative predictive value (100%) and accuracy (93%) in predicting the persistence of rSHPT. CONCLUSIONS: The monitoring of the ioPTH decline by a low cost central-laboratory second generation assay is extremely accurate in predicting the persistence of disease in patients on maintenance hemodialysis undergoing surgery for rSHPT

Background: Functional impairment is associated with adverse outcomes in older people, as well as in patients on chronic hemodialysis. The aim of the present study was to determine the characteristics associated with functional impairment in chronic hemodialysis, and to evaluate if functional impairment represents a risk factor for reduced survival in chronic hemodialysis. Methods: All 132 chronic hemodialysis referring to the Hemodialysis Service of the Catholic University, Rome, Italy between November 2007 and May 2015 were included. All patients underwent comprehensive geriatric assessment; functional ability was estimated using two questionnaires exploring independency in bathing, dressing, toileting, transferring, continence, feeding (ADLs), and independency in using the telephone, shopping, food preparation, housekeeping, laundering, traveling, taking medications, and handling finances (IADLs). Functional impairment was diagnosed in presence of dependence in one or more ADLs/IADLs. Mood was assessed using the 30-item Geriatric Depression Scale. Logistic regression was used to evaluate factors associated with functional impairment. The association between functional impairment and survival was assessed by Cox regression. Results: ADLs impairment was present in 34 (26 %) participants, while IADLs impairment was detected in 64 (48 %) subjects. After a follow up of 90 months, 55 (42 %) patients died. In logistic regression, depressive symptoms were associated with ADLs and IADLs impairment (OR 1.12; 95 % CI = 1.02-1.23; OR 1.16; 95 % CI = 1.02-1.33; respectively). In Cox regression, ADLs impairment was associated with mortality (HR 2.47; 95 % CI-1.07-5.67) while IADLs impairment was not associated with reduced survival (HR .80; 95 % CI-.36-1.76). Conclusions: Functional impairment is associated with depressive symptoms; also, impairment in the ADLs represents a risk factor of reduced survival in chronic hemodialysis. These associations and their potential implicat

Objectives: To compare the CACS and CAD severity assessed by MDCT in neuropathic type-2 diabetic patients with and without Charcot-neuroarthropathy (CN). Methods: Thirty-four CN asymptomatic-patients and 36 asymptomatic-patients with diabetic-neuropathy (DN) without CN underwent MDCT to assess CACS and severity of CAD. Patients were classified as positive for significant CAD in presence of at least one stenosis >50 % on MDCT-coronary-angiography (MDCT-CA). Groups were matched for age, sex and traditional CAD risk-factors. The coronary-angiography (CA) was performed in all patients with at least a significant stenosis detected by MDCT-CA, both as reference and eventually as treatment. Results: CN patients showed higher rates of significant CAD in comparison with DN subjects [p < 0.001], while non-significant differences were observed in CACS (p = 0.980). No significant differences were also observed in CACS distribution in all subjects for stenosis ≥/<50 % (p = 0.814), as well as in both groups (p = 0.661 and 0.559, respectively). The MDCT-CA showed an overall diagnostic-accuracy for significant CAD of 87 %. Conclusions: These preliminary data suggest that CN-patients have a higher prevalence of severe CAD in comparison with DN-patients, while coronary plaques do not exhibit an increased amount of calcium. MDCT may be helpful to assess the CV risk in such asymptomatic type-2-diabetic patients with autonomic-neuropathy. Key Points: • Type 2-diabetic-patients with CN result having more severe coronary artery plaque-burden. • MDCT-CA may stratify the CV risk in type 2-diabetic-patients with CN. • Adequate diagnostic is mandatory for optimal management of type 2-diabetic-patients with CN.

Objectives: A systematic review was conducted to assess the effectiveness of MRI in evaluating upper airway structures in children affected by obstructive sleep apnoea syndrome (OSAS). Methods: A literature search was performed in the Cochrane Central Register of Controlled Trials, Web of Science, Scopus and PubMed databases from their inception to 31/03/2016, including available randomized controlled trials and controlled clinical trials published in English assessing the use of MRI integrated with traditional polysomnography (PSG) among children up to 15 years of age affected by OSAS. The primary outcome to be evaluated was the efficacy of MRI in analyzing the upper airway total volume among healthy children compared with children affected by OSAS. Secondary outcomes were to compare the efficacy of MRI in analyzing the upper airway cross-sectional area in the areas adjacent to the adenoids and tonsils, adenoid and tonsil volume, and soft-tissue and maxillofacial bone parameters in the same sample. Results were expressed using a random-effects model and mean differences (MD) with 95% confidence intervals (CI). Results: The search yielded 1005 titles in total; the selection process narrowed to 3 titles, which were all assessed as indicating an unclear level of risk of bias. The meta-analysis found evidence of MRI effectiveness in evaluating differences in the upper airway total volume between paediatric patients affected by OSAS and paediatric patients not affected by OSAS (MD 20.56 cm3; 95% CI: 21.05 to 20.07). Conclusions: Although MRI could be considered effective in evaluating upper airway structures in children affected by OSAS, based on the present evidence, PSG is still the golden standard and further studies are required to verify MRI reliability. © 2016 The Authors. Published by the British Institute of Radiology.

BACKGROUND CONTEXT: Back pain at a young age is considered to be predictive of chronicity. Several studies have investigated the relationship between the use of a schoolbag and back pain, although some aspects are still unclear. PURPOSE: The aim of this study was to evaluate back pain due to schoolbag use in terms of (1) prevalence and intensity, (2) differences between male and female pupils, and (3) predisposing factors. STUDY DESIGN: This is a cross-sectional study. PATIENT SAMPLE: The sample was composed of 5,318 healthy pupils aged 6 to 19 years (classified according to three age groups: children, younger adolescents, and older adolescents). OUTCOME MEASURES: Schoolbag-related pain was assessed by means of an ad hoc questionnaire. The intensity of pain was assessed using the Wong scale. METHODS: Subjects underwent a face-to-face interview using an ad hoc questionnaire. The intensity of pain was assessed using the Wong scale. On the basis of the prevalence and intensity of back pain, we divided our population into two groups: (1) no or mild pain group and (2) moderate or severe pain group. The "schoolbag load" (ratio between schoolbag and pupil weight multiplied by 100) was calculated for each subject. RESULTS: More than 60% of the subjects reported pain. Although the schoolbag load decreased from children to young and older adolescents, schoolbag-related pain significantly increased (p<.001). Girls reported significantly more frequent and more severe pain than boys. The logistic model confirmed that adolescent girls are the group at greatest risk of suffering from intense pain. The schoolbag load had a weak impact on back pain, whereas the schoolbag carrying time was a strong predictor. CONCLUSIONS: Adolescent girls have the highest risk of experiencing severe back pain, regardless of schoolbag load. This suggests that other factors (anatomical, physiological, or environmental) might play an important role in pain perception. These aspects should be investigate

Background: Laser ablation may be useful in debulking of benign thyroid nodules. Methods: To evaluate retrospectively the effectiveness and safety of LA, 45 patients with benign solid thyroid nodules, with a fluid component ≤20%, were included in our series between October 2009 and January 2011. All reported pressure and/or cosmetic complaints. Nd:YAG laser at 1064 nm was used, with a fix-power (3W), changing the application time. All patients were evaluated at baseline, 6 and 12 months. Complications were recorded. Results: mean nodule volume reduction decreased from 24.2 mL ±19.4 to 4.5 ± 5.2 at 12 months (p<0.001). Mean nodule volume reduction was 84% ± 13. Cosmetic signs were completely resolved in 87%, reduced in 9%, unchanged in 2%; pressure symptoms were resolved in 88%. One patient experienced transient dysphonia. Conclusions: US-guided LA is an effective tool for treatment of symptomatic benign thyroid nodules in patients not eligible for surgery. This article is protected by copyright. All rights reserved.

BACKGROUND Subcutaneous fat represents a valuable reservoir of adipose-derived stem cells(ASCs) in the stromal vascular fraction (SVF), widely exploited in regenerative medicine applications, being easily harvested through lipoaspiration. The lack for standardized procedures for autologous fat grafting, guided research efforts aimed at identifying possible differences related to the harvesting site, affecting cell isolation yield, cell growth properties and clinical outcomes. Subcutaneous fat features a complex architecture: the superficial fascia separates superficial adipose tissue (SAT) from deep layer (DAT). We aimed to unravel the differences between SAT and DAT, considering morphological structure, SVF composition and ASCs’ properties. METHODS SAT and DAT were collected from female donors and comparatively analyzed to evaluate cellular yield and viability, morphology, immunophenotype and molecular profile. ASCs were isolated in primary culture and used for in vitro differentiation assays. SAT and DAT from cadaver donors, were also analyzed through histology and immunohistochemistry, to assess morphology and cell localization within the hypoderm. RESULTS liposucted SAT contained a higher stromal tissue compound, along with a higher proportion of CD105-positive cells, compared to DAT from the same harvesting site. Also, cells isolated from SAT displayed increased multipotency and stemness features. All differences were mainly evidenced in specimens harvested from the abdominal region. According to our results, SAT features overall increased stem properties. DISCUSSION Given that subcutaneous adipose tissue is currently exploited as the gold standard source for high yield isolation of somatic adult stem cells, these results may provide precious hints toward the definition of standardized protocols for microharvesting.

BACKGROUND AIMS: Subcutaneous fat represents a valuable reservoir of adipose-derived stem cells (ASCs) in the stromal vascular fraction (SVF), widely exploited in regenerative medicine applications, being easily harvested through lipoaspiration. The lack of standardized procedures for autologous fat grafting guided research efforts aimed at identifying possible differences related to the harvesting site, which may affect cell isolation yield, cell growth properties and clinical outcomes. Subcutaneous fat features a complex architecture: the superficial fascia separates superficial adipose tissue (SAT) from deep layer tissue (DAT). We aimed to unravel the differences between SAT and DAT, considering morphological structure, SVF composition, and ASC properties. METHODS: SAT and DAT were collected from female donors and comparatively analyzed to evaluate cellular yield and viability, morphology, immunophenotype and molecular profile. ASCs were isolated in primary culture and used for in vitro differentiation assays. SAT and DAT from cadaver donors were also analyzed through histology and immunohistochemistry to assess morphology and cell localization within the hypoderm. RESULTS: Liposuctioned SAT contained a higher stromal tissue compound, along with a higher proportion of CD105-positive cells, compared with DAT from the same harvesting site. Also, cells isolated from SAT displayed increased multipotency and stemness features. All differences were mainly evidenced in specimens harvested from the abdominal region. According to our results, SAT features overall increased stem properties. CONCLUSIONS: Given that subcutaneous adipose tissue is currently exploited as the gold standard source for high-yield isolation of adult stem cells, these results may provide precious hints toward the definition of standardized protocols for microharvesting.

Melanoma is highly curable in early stages but holds devastating consequences in advanced phases with a median survival of 6-10 months. Lungs are a common metastasis target, but despite this, limited data are available on the molecular status of pulmonary lesions.

Image-guided laser ablation therapy (LAT) of benign thyroid nodules demonstrated favorable results in randomized trials with fixed modalities of treatment. The aim of this retrospective multicenter study was to assess the effectiveness, tolerability, and complications of LAT in a large consecutive series of patients from centers using this technique in their routine clinical activity.

A new rapid, automatic, and sensitive screening test useful to detect cryoglobulins in serum samples is proposed.

In recent years, Botulinum Toxin has been shown to be efficacious and safe in the treatment of sialorrhea, but scanty data are available on its long term use. The aim of this study was to investigate adverse events, discriminate differences in safety, and evaluate the efficacy of long-term use of both abobotulinumtoxinA and rimabotulinumtoxinB ultrasound-guided injections for sialorrhea in a retrospective trial. Moreover we review the literature on this topic.

A better knowledge of the fatigue could be of the greatest importance for the high-grade glioma (HGG) patients, who are a unique and vulnerable population. The aim of this study was to evaluate the occurrence and the predictors of the fatigue in HGG patients, using a specific fatigue scale. The study was designed as a cross-sectional study. The study population included sixty-seven consecutive outpatients with HGG. We used these measures: Brief Fatigue Inventory, Karnofsky Performance Scale, Functional Independence Measure, Brief Psychiatric Rating Scale and Psychological Distress Inventory and SF-36, EORTC QLQ-30 and EORTC QLQ-BN20 for quality of life (QoL). Sixteen out of sixty-seven (23.9 %) patients were affected by Anaplastic Astrocytoma and 51/67 (76.1 %) by Glioblastoma Multiforme. About one-third (36.2 %) of patients had a clinically relevant fatigue (Brief Fatigue Inventory ≥3). In regression analysis, physical and mental aspects of QoL were statistically significant related with fatigue (p < 0.01 and p < 0.02, respectively). Our data underlined the relevant occurrence of fatigue in HGG patients and support the development of further studies exploring a tailored rehabilitation program.

Little is known about activated immune-inflammatory pathways and interleukin-6 (IL-6) in the development of fatigue and/or depression in patients with end-stage renal disease on chronic hemodialysis (HD).