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Objectives: To determine the association of adequate empirical combination therapy (AECT) with 30-day all-cause mortality in patients with septic shock due to Pseudomonas aeruginosa bloodstream infections (BSI)., Methods: This multicentre, retrospective cohort study analysed data from 14 public hospitals in Italy, including all consecutive adult patients admitted during 2021-2022 with septic shock due to P. aeruginosa BSI. We compared the outcomes of patients receiving AECT to those on adequate empirical monotherapy (AEMT) using Cox regression analyses., Results: Of the 98 patients who received adequate empirical antibiotic treatment for septic shock due to P. aeruginosa BSI, 24 underwent AECT and 74 were given AEMT. AECT was associated with a lower 30-day all-cause mortality (25%, six out of 24) compared to AEMT (56.8%, 42 out of 74; P = 0.007). Multivariate Cox regression analysis indicated AECT as the only factor significantly associated with improved survival (aHR 0.30; 95% CI 0.12-0.71; P = 0.006). By contrast, the use of monotherapy or combination therapy in the definitive regimen did not influence mortality (aHR 0.73; 95% CI 0.25-2.14; P = 0.568)., Conclusions: AECT may be associated with reduced mortality compared to monotherapy in septic shock patients due to P. aeruginosa BSI. However, the administration of definitive adequate monotherapy or combination therapy yields similar outcomes, suggesting that once susceptibility is documented, switching to a single active in vitro drug is safe and feasible. Further studies are recommended to validate these findings., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Systemic steroids are recommended for patients with IgA nephropathy (IgAN) and proteinuria. However, there are concerns about their safety due to an excess of serious adverse events (SAEs) in previous randomised trials. This study evaluates the incidence of SAEs in IgAN patients receiving different treatment regimens in clinical practice., Methods: Multicentre, retrospective, observational cohort study of 1209 patients (M/F: 864/345, mean age: 41.73 ± 14.92 years) with biopsy-proven IgAN treated with renin angiotensin system (RAS) inhibitors (RASI) (n = 285), intravenous + oral steroids (n = 633), oral steroids (n = 99), steroids + immunosuppressants (n = 192)., Results: A total of 119 (9.8%) adverse events were reported, of which 67 (5.5%) were considered treatment-emergent, and 36 (2.9%) were SAEs (n = 23, 63.8% were infections). One patient died due to sepsis. A significant association was observed between AEs and immunosuppression [8 (2.8%) in RASI, 60 (9.4%) in steroids + immunosuppressants, 14 in oral steroids (14.1%) and 37 pts (19.2%) in steroids + immunosuppressants (p < 0.01)], age and estimated glomerular filtration rate (eGFR), but not with proteinuria and sex. On multivariate analysis, only older age was associated with the occurrence of SAEs., Conclusions: According to our findings, the incidence of SAEs during therapy with steroids alone or associated with immunosuppressors is lower in everyday clinical practice than in randomised clinical trials., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Aims: After an ischaemic stroke, atrial fibrillation (AF) detection allows for improved secondary prevention strategies. This study aimed to compare AF detection and oral anticoagulant (OAC) initiation in patients with an insertable cardiac monitor (ICM) vs. external cardiac monitor (ECM) after ischaemic stroke., Methods and Results: Medicare Fee-for-Service (FFS) insurance claims and Abbott Labs device registration data were used to identify patients hospitalized with an ischaemic stroke in 2017-2019 who received an ICM or ECM within 3 months. Patients with continuous Medicare FFS insurance and prescription drug enrolment in the prior year were included. Patients with prior AF, atrial flutter, cardiac devices, or OAC were excluded. Insertable cardiac monitor and ECM patients were propensity score matched 1:4 on demographics, comorbidities, and stroke hospitalization characteristics. The outcomes of interest were AF detection and OAC initiation evaluated with Kaplan-Meier and Cox proportional hazard regression analyses. A total of 5702 Medicare beneficiaries (ICM, n = 444; ECM, n = 5258) met inclusion criteria. The matched cohort consisted of 2210 Medicare beneficiaries (ICM, n = 442; ECM, n = 1768) with 53% female, mean age 75 years, and mean CHA₂DS₂-VASc score 4.6 (1.6). Insertable cardiac monitor use was associated with a higher probability of AF detection [(hazard ratio (HR) 2.88, 95% confidence interval (CI) (2.31, 3.59)] and OAC initiation [HR 2.91, CI (2.28, 3.72)] compared to patients monitored only with ECM., Conclusion: Patients with an ischaemic stroke monitored with an ICM were almost three times more likely to be diagnosed with AF and to be prescribed OAC compared to patients who received ECM only., Competing Interests: Conflict of interest: G.B. received small speaker’s fees from Abbott, Bayer, Boston, Boehringer, Daiichi Sankyo, Janssen, and Sanofi, outside of the submitted work. A.A, is a consultant to Abbott, Boston Scientific, Cairdac, EP Solutions, Hylomorph, Medtronic, and XSpline; has received speaker fees from Boston Scientific, Medtronic, Microport CRM, and Philips; participates in clinical trials sponsored by Abbott, Boston Scientific, EPD-Philips, EP Solutions, Medtronic, Philips, and XSpline; and holds intellectual properties with Boston Scientific, Biosense Webster, and Microport CRM. G.L.B. has received speaker fees (small amount) from Abbott, Biotronik, Boston Scientific, Medtronic, and Microport CRM. J.P.P. is supported by R01AG074185 from the National Institutes of Aging. He also receives grants from Abbott, the American Heart Association, the Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, iRhythm, and Philips and serves as a consultant to Abbott, Abbvie, ARCA biopharma, Bayer, Boston Scientific, Element Science, LivaNova, Medtronic, Milestone, ElectroPhysiology Frontiers, Sanofi, Philips, and Up-to-Date. J.M.J., G.J.R., A.G., and Y.N. are employed by Abbott., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Although radiofrequency (RF) catheter ablation of cavo-tricuspid isthmus (CTI) is an established treatment for typical right atrial flutter (RAFL), it remains to be established whether local tissue impedance (LI) is able to predict effective CTI ablation and what LI drop values during ablation should be used to judge a lesion as effective. We aimed to investigate the ability of LI to predict ablation efficacy in patients with RAFL., Methods: RF delivery was guided by the DirectSense™ algorithm. Successful single RF application was defined according to a defragmentation of atrial potentials (DAP), reduction of voltage (RedV) by at least 80% or changes on unipolar electrogram (UPC). The ablation endpoint was the creation of bidirectional conduction block (BDB) across the isthmus., Results: 392 point-by-point RF applications were analyzed in 48 consecutive RAFL patients. The mean baseline LI was 105.4 ± 12Ω prior to ablation and 92.0 ± 11Ω after ablation (p < 0.0001). According to validation criteria, absolute drops in impedance were larger at successful ablation sites than at ineffective ablation sites (DAP: 17.8 ± 6Ω vs. 8.7 ± 4Ω; RedV: 17.2 ± 6Ω vs. 7.8 ± 5Ω; UPC: 19.6 ± 6Ω vs. 10.1 ± 5Ω, all p < 0.0001). LI drop values significantly increased according to the number of criteria satisfied (ranging from 7.5Ω to 19.9). BDB was obtained in all cases. No procedure-related adverse events were reported., Conclusions: A LI-guided approach to CTI ablation was safe and effective in treating RAFL. The magnitude of LI drop was associated with effective lesion formation and BDB and could be used as a marker of ablation efficacy., Clinical Trial Registration: Catheter Ablation of Arrhythmias with a High-Density Mapping System in Real-World Practice (CHARISMA). URL: http://clinicaltrials.gov/ Identifier: NCT03793998., (© 2022 Wiley Periodicals LLC.)

Background: Long-term pulmonary sequelae following hospitalization for SARS-CoV-2 pneumonia is largely unclear. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 12-month from discharge., Methods: In this multicentre, prospective, observational study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support ("oxygen only", "continuous positive airway pressure (CPAP)" and "invasive mechanical ventilation (IMV)") and followed up at 12 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 min walking test, high resolution CT (HRCT) scan, and modified Medical Research Council (mMRC) dyspnea scale were collected., Results: Out of 287 patients hospitalized with SARS-CoV-2 pneumonia and followed up at 1 year, DLCO impairment, mainly of mild entity and improved with respect to the 6-month follow-up, was observed more frequently in the "oxygen only" and "IMV" group (53% and 49% of patients, respectively), compared to 29% in the "CPAP" group. Abnormalities at chest HRCT were found in 46%, 65% and 80% of cases in the "oxygen only", "CPAP" and "IMV" group, respectively. Non-fibrotic interstitial lung abnormalities, in particular reticulations and ground-glass attenuation, were the main finding, while honeycombing was found only in 1% of cases. Older patients and those requiring IMV were at higher risk of developing radiological pulmonary sequelae. Dyspnea evaluated through mMRC scale was reported by 35% of patients with no differences between groups, compared to 29% at 6-month follow-up., Conclusion: DLCO alteration and non-fibrotic interstitial lung abnormalities are common after 1 year from hospitalization due to SARS-CoV-2 pneumonia, particularly in older patients requiring higher ventilatory support. Studies with longer follow-ups are needed., (© 2022. The Author(s).)

Thromboembolism is the most serious complication of AF, and oral anticoagulation is the mainstay therapy. Current guidelines place all AF types together in terms of anticoagulation with the major determinants being associated comorbidities translated into risk marker. Among patients in large clinical trials, those with non-paroxysmal AF appear to be at higher risk of stroke than those with paroxysmal AF. Higher complexity of the AF pattern is also associated with higher risk of mortality. Moreover, continuous monitoring of AF through cardiac implantable devices provided us with the concept of 'AF burden'. Usually, the larger the AF burden, the higher the risk of stroke; however, the relationship is not well characterised with respect to the threshold value above which the risk increases. The picture is more complex than it appears: AF and underlying disorders must act synergically respecting the magnitude of its own characteristics, which are the amount of time a patient stays in AF and the severity of associated comorbidities., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © 2021, Radcliffe Cardiology.)

Background: Long-term pulmonary sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia are not yet confirmed; however, preliminary observations suggest a possible relevant clinical, functional, and radiological impairment., Objectives: The aim of this study was to identify and characterize pulmonary sequelae caused by SARS-CoV-2 pneumonia at 6-month follow-up., Methods: In this multicentre, prospective, observational cohort study, patients hospitalized for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support ("oxygen only," "continuous positive airway pressure," and "invasive mechanical ventilation") and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6-min walking test, chest X-ray, physical examination, and modified Medical Research Council (mMRC) dyspnoea score were collected., Results: Between March and June 2020, 312 patients were enrolled (83, 27% women; median interquartile range age 61.1 [53.4, 69.3] years). The parameters that showed the highest rate of impairment were DLCO and chest X-ray, in 46% and 25% of patients, respectively. However, only a minority of patients reported dyspnoea (31%), defined as mMRC ≥1, or showed restrictive ventilatory defects (9%). In the logistic regression model, having asthma as a comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalization appeared as a protective factor. The need for invasive ventilatory support during hospitalization was associated with chest imaging abnormalities., Conclusions: DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with the coronavirus disease 2019 (COVID-19) during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae., (© 2021 S. Karger AG, Basel.)

Background: The Aphasia Rapid Test (ART) is a screening questionnaire used for examining language in acute stroke patients. The ART was initially developed and validated in French. The purpose of this study was to assess the inter-rater reliability of Italian ART., Methods: The original version of the ART was translated into Italian. The inter-rater reliability was assessed by two independent neurologists who were blind to each other's ratings in 52 acute post-stroke patients., Results: The 52 patients (28 men, 24 women; mean age 73.73 ± 28.99 years) were included within 1 week of stroke onset (46 ischemic, 6 hemorrhagic), as assessed by clinical examination and confirmed by CT and/or MRI. The mean (± SD) ART value was 9.38 (± 9.26) for rater 1 and 9 (±9.31) for rater 2. The inter-rater agreement was very good, with a coefficient of concordance of 0.99 (95% CI 0.986-0.995; p < 0.0001) and a weighted kappa of 0.878 and a quadratic weighted kappa of 0.983., Conclusions: This study showed that the cross-cultural adaptation of the French version of the ART was successful in an Italian-speaking population.

In 2007, Società Italiana di Ecocardiografia e CardioVascular Imaging (SIECVI) already SIEC, published the document on the organization of echocardiography in Italy. In the years following the technological evolution, cultural and health factors have changed "the way, we do echo" as a tool for the different clinical pathways. The SIECVI Accreditation Area and Board 2017-2019 considered necessary to review and update the document in the light of innovation in the application of ultrasound for the heart disease assessment. In the document, we have considered the role of SIECVI in multimodal imaging, the need of training and certification of operators, the quality of echo machines, the accreditation of laboratories, the compilation of the report and its responsibility, and the presence of the sonographers in the EchoLab., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Cardiovascular Echography.)

Background: Recently we defined a user-friendly tool (FADOI-COMPLIMED scores-FCS) to assess complexity of patients hospitalized in medical wards. FCS-1 is an average between the Barthel Index and the Exton-Smith score, while FCS-2 is obtained by using the Charlson score. The aim of this paper is to assess the ability of the FCS to predict mortality in-hospital and after 1-3-6-12-months. In this perspective, we performed comparisons with the validated Multidimensional Prognostic Index (MPI)., Methods: It is a multicenter, prospective observational study, enrolling patients aged over 40, suffering from at least two chronic diseases and consecutively admitted to Internal Medicine departments. For each patient, data from 13 questionnaires were collected. Survival follow-up was conducted at 1-3-6-12 months after discharge. The relationships between cumulative incidences of death with FCS were investigated with logistic regression analyses. ROC curve analyses were performed in order to compare the predictiveness of the logistic models based on FCS with respect to those with MPI taken as reference., Results: A cohort of 541 patients was evaluated. A 10-point higher value for FCS-1 and FCS-2 leads to an increased risk of 1-year death equal to 25.0% and 27.1%, respectively. In case of in-hospital mortality, the relevant percentages were 63.1% and 15.3%. The logistic model based on FCS is significantly more predictive than the model based on MPI (which requires an almost doubled number of items) for all the time-points considered., Conclusions: Assessment of prognosis of patients has the potential to guide clinical decision-making and lead to better care. We propose a new, efficient and easy-to-use instrument based on FCS, which demonstrated a good predictive power for mortality in patients hospitalized in medical wards. This tool may be of interest for clinical practice, since it well balances feasibility (requiring the compilation of 34 items, taking around 10 minutes) and performance., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: There are no conflicts of interest.

Objective: To evaluate the additive and independent prognostic value of abnormal right ventricle (aRV) and pulmonary hypertension (PH) in patients undergoing mitral-tricuspid surgery., Methods: From January 2009 to December 2012, 541 patients underwent mitro-tricuspid surgery. The entire cohort was divided into 6 subgroups: 63 cases had normal RV and no PH (Group A), 180 normal RV but moderate PH (Group B), 101 normal RV but severe PH (Group C), 15 abnormal RV and no-PH (Group D), 86 abnormal RV and moderate PH (Group E) and 96 abnormal RV and severe PH (Group F)., Results: Forty-two (7.8%) patients died in hospital due to any cause: 1.6% in group A, 3.9% in group B, 8.9% in group C, 13.3% in group D, 9.3% in group E, 15.6% in group E, p = 0.005. Among 78 patients with no-PH, mortality was significantly higher in patients with aRV (1.6%vs 13.3%. p = 0.03). Among 344 patients with normal RV, mortality was significantly higher in patients with severe PH (1.6% vs 3.9% vs 8.9%. p = 0.03). Comparing the presence of both abnormal RV and severe PH with the remaining patients, mortality was significantly higher in the first group (15.6% 6.1%, p = 0.004). Multivariable analysis confirmed either the independent or the additive role of RV and PH., Conclusions: In patients undergoing mitral-tricuspid valve surgery, the presence of either RV dysfunction/dilatation or severe pulmonary hypertension, might play an independent prognostic role for mortality. The worst scenario is surely the contemporary presence of both conditions.

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystemic disorder caused by deregulation of the mTOR pathway, and represents one of the leading genetic causes of epilepsy. mTOR inhibitors (Sirolimus and Everolimus) are currently approved only for the treatment of growing subependymal giant cell astrocytomas, renal angiomyolipomas and lymphangioleiomyomatosis in TSC. However, preclinical and clinical evidence supports their potential role in effectively treating TSC-associated epilepsy, but no consensus on its use in seizures has been reached yet and there are few data on epilepsy outcome after the suspension of mTOR inhibitors treatment. We report for the first time on a patient in whom discontinuation of Everolimus (prescribed for growing subependymal giant cell astrocytomas) was associated with a relapse of seizures twice, and control of seizures was regained after reintroducing the medicine. This clinical report supports the promising potential of Everolimus in treating epilepsy in TSC, and specifically underlines the non-permanent effect on seizures after withdrawal., (Copyright © 2017. Published by Elsevier Ltd.)

Background: The original peritoneal equilibration test (PET) was used to classify peritoneal dialysis (PD) patients using a 2.27% glucose solution. It has since been suggested that a 3.86% glucose solution be used because this provides better information about ultrafiltration (UF) capacity and the sodium (Na) sieving of the peritoneal membrane., Objective: The aim of this study was to determine reference values for a PET using a 3.86% glucose solution (PET-3.86%)., Methods: We evaluated the PET-3.86% in a large population of incident PD patients attending 27 Italian dialysis centers., Results: We evaluated the results of 758 PET-3.86% in 758 incident PD patients (1 test per patient). The mean duration of PD was 5 ± 3 months. The ratio of the concentrations of creatinine in dialysate/plasma (D/P Creat ) was 0.73 ± 0.1 (median 0.74). The ratio between the concentrations of glucose at the end/beginning of the test (D/D 0 ) was 0.25 ± 0.08 (median 0.24). Ultrafiltration uncorrected and corrected for bag overfill was respectively 776 ± 295 mL (median 781 mL) and 675 ± 308 mL (median 689 mL). Sodium sieving was 8.4 ± 3.8 mmol/L (median 8.0 mmol/L)., Conclusion: The results of the study provide PET-3.86% reference values for the beginning of PD that can be used to classify PD patients into transport classes and monitor them over time., (Copyright © 2017 International Society for Peritoneal Dialysis.)

The chronic course and evolution of chronic obstructive pulmonary disease (COPD) is often characterized by periods of exacerbation of symptoms, which have a negative impact on the quality of life of patients, as well as on the evolution of COPD, and represent a significant cause of medical intervention and hospitalization. Very few data are available on the efficacy of rescue antibiotics in patients with acute exacerbation of COPD (AECOPD) unresponsive to previous treatment. The aim of this study was to evaluate the efficacy of two fluoroquinolones in AECOPD previously treated without success. The FADOI-FLOR study is a randomized, single-blind, non-inferiority comparison between levofloxacin and prulifloxacin. Primary end-point was "therapeutic success" at Day 10 of treatment, defined as disappearance of signs/symptoms or decrease of at least three points of a global score of symptomatology (maximum score = 15). 258 patients were enrolled (128 levofloxacin and 130 prulifloxacin), in 25 centers. A very high proportion of patients in the two groups had therapeutic success at Day-10 (levofloxacin 93.0% vs prulifloxacin 96.7%, population intention-to-treat; 94.6% vs 99.1%, population per-protocol). Earlier therapeutic success (within 7 days) was achieved in 32.0% and 36.2% of patients receiving levofloxacin or prulifloxacin, respectively. At 3-month follow-up, re-exacerbations occurred in 17.8% of patients treated with levofloxacin and 14.2% of those receiving prulifloxacin (p = 0.44). In conclusion, fluoroquinolones are very effective in the treatment of AECOPD resistant to other antibiotics.

Background: The aim of this work is to develop an algorithm to predict recurrence in prostate cancer patients treated with radical radiotherapy, getting up to a prognostic power higher than traditional D'Amico risk classification., Methods: Two thousand four hundred ninety-three men belonging to the EUREKA-2 retrospective multi-centric database on prostate cancer and treated with external-beam radiotherapy as primary treatment comprised the study population. A Cox regression time to PSA failure analysis was performed in univariate and multivariate settings, evaluating the predictive ability of age, pre-treatment PSA, clinical-radiological staging, Gleason score and percentage of positive cores at biopsy (%PC). The accuracy of this model was checked with bootstrapping statistics. Subgroups for all the variables' combinations were combined to classify patients into five different "Candiolo" risk-classes for biochemical Progression Free Survival (bPFS); thereafter, they were also applied to clinical PFS (cPFS), systemic PFS (sPFS) and Prostate Cancer Specific Survival (PCSS), and compared to D'Amico risk grouping performances., Results: The Candiolo classifier splits patients in 5 risk-groups with the following 10-years bPFS, cPFS, sPFS and PCSS: for very-low-risk 90 %, 94 %, 100 % and 100 %; for low-risk 74 %, 88 %, 94 % and 98 %; for intermediate-risk 60 %, 82 %, 91 % and 92 %; for high-risk 43 %, 55 %, 80 % and 89 % and for very-high-risk 14 %, 38 %, 56 % and 70 %. Our classifier outperforms D'Amico risk classes for all the end-points evaluated, with concordance indexes of 71.5 %, 75.5 %, 80 % and 80.5 % versus 63 %, 65.5 %, 69.5 % and 69 %, respectively., Conclusions: Our classification tool, combining five clinical and easily available parameters, seems to better stratify patients in predicting prostate cancer recurrence after radiotherapy compared to the traditional D'Amico risk classes.

Background: Neonatal seizures are a risk factor for later epilepsy and their etiology is known to be implicated in the outcome but, little is known about this issue in the subgroup of seizures symptomatic of perinatal arterial ischemic stroke. The aim of this study was to describe the long term risk of epilepsy after electroencephalographic confirmed neonatal seizures symptomatic of perinatal arterial ischemic stroke., Design/subject: Fifty-five patients with electroclinical ictal data, vascular territory confirmed by neuroimaging and a minimum follow up of 3.5 years were identified from a multi-centre prospective neonatal seizures registry. Primary outcome was occurrence of post-neonatal epilepsy. The association of outcome with family history of epilepsy, gender, location of the infarct, neonatal clinical and electroencephalogram data were also studied., Results: During a mean follow up of 8 years and 5 months, 16.4% of the patients developed post neonatal epilepsy. The mean age at first post neonatal seizure was 4 years and 2 months (range 1-10 years and 6 months). Location of the infarct was the only statistically significant risk factor (p=0.001); epilepsy was more represented in males but the difference was not statistically significant., Conclusions: Neonatal seizures symptomatic of perinatal arterial ischemic stroke had lower risk and later onset of post-neonatal epilepsy, compared to seizures described in the setting of other perinatal brain insults. Our data have implications for counseling to the family at discharge from neonatal intensive care unit., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Prostate cancer (PCa) is the fourth most common cancer worldwide in terms of incidence and third among male, but is becoming the most common cancer in developed countries. In many patients the disease will progress despite of castration levels of testosterone, to become castration-resistant PCa (CRPC). Nearly all patients with CRPC show bone metastases. The treatment of patients with bony metastases has dramatically changed during the past three years because of new therapeutic approaches addressed to obtain pain control, reduced skeletal morbidity, and most importantly, increased survival rate. A possible therapy can be based also on the use of radiopharmaceuticals systemically administered to slow or reverse the bone metastatic progression. In facts bone-homing radiopharmaceuticals are taken up in areas of high bone turnover, including areas with high osteoblastic activity. Recently, a bone targeting radiopharmaceutical, Radium-223 dichloride was added to this group of drugs clearly representing a new generation of radiopharmaceutical in bone therapy. Clinical trials had shown that the treatment with Ra-223 allowed the reduction of the risk of death respect to placebo. No other radiometabolic treatment achieved such result, evidentiating the disease-modifying properties of this bone-homing radiopharmaceutical. In an effort to treat patients with disseminated PCa, who became resistant to hormonal therapy, molecular targets have been recently identified. Prostate specific membrane antigen (PSMA) is one attractive target for diagnosis and therapy of metastasized PCa since its expression levels are directly correlated to androgen independence, metastasis, and progression. Gastrin-releasing peptide receptors (GRPr) are also highly overexpressed in PCa. Numerous studies suggest the possibility of a high PCa-specific signal with radiolabeled bombesin analogs targeting GRPr. Low molecular weight peptides directed against these molecular targets have been radiolabeled with positron emitting radionuclides such as 68Ga in order to improve sensitivity and specificity for detecting primary, metastatic, and recurrent PCa by PET/CT over conventional imaging techniques. Although peptide radionuclide ligand therapy studies have just initiated, the diagnostic relevance of 68Ga labeled specific tracers has already been established its clinical utility and represents a valid tool against this common and deadly cancer.

Objectives: To evaluate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and the presence of a Chronic Venous Disorder (CVD)., Method: We included 55 subjects with CCSVI aged >18 years, and 186 controls without CCSVI. Each subject was evaluated with color Doppler sonography in accordance with Zamboni's five criteria, examined by two neurologists and interviewed with an ad-hoc designed form. The neurologists and the sonographers were mutually blinded. CVD were classified according to CEAP., Results: Mean age was 42 years (SD = 9) in cases and 43 years (10) in controls (p = ns). The odds ratios in subjects CCSVI were 0.6 (0.2-2.2) for CEAP 1, 0.9 (0.2-4.5) for CEAP 2, and 1.0 (0.6-1.9) for family history of varicose veins. The prevalence of CVD and, family history of varicose veins, was similar between cases and controls for each Zamboni criterion., Conclusions: We found no association of CCSVI with the presence of CVD or family history of varicose veins., (© The Author(s) 2014.)

Background: To evaluate evidence and prognosis of refractory cases of absence seizures., Methods: Subjects with refractory absence seizures were identified retrospectively in 17 Italian epilepsy pediatrics Centers. We analyzed age at onset, family history, presence of myoclonic components, seizure frequency, treatment with antiepileptic drugs (AEDs), interictal electroencephalography (EEG) and neuropsychological assessment. Two subgroups were identified: one with patients with current absence seizures and another with patients that had become seizure free with or without AED treatment. The chi-square test was applied., Results: A total of 92 subjects with drug-resistant absence seizures were analyzed. 45 subjects still show absence seizures (49%) and the other 47 became seizure free (51%) after a period of drug-resistance. The statistical analysis between these two groups showed no correlation between age of onset, family history and abnormalities at interictal EEG. Statistically significant differences were observed with regard to the number of AEDs used and intellectual disability., Conclusion: Typical absence epilepsy classifiable as Childhood Absence Epilepsy could not be considered so "benign", as suggested in literature. A longer duration of disease and a higher frequency of seizure seem to be correlated with a higher presence of cognitive impairment. No significant risk factor was observed to allow the faster and better recognition of patients with worse prognosis., (Copyright © 2015. Published by Elsevier Ltd.)

Background: Osteoporotic vertebral fractures (VFs) often go unrecognised in both healthy individuals and in pathological conditions. Few data exist on VFs in patients hospitalised in Internal Medicine Units (IMUs), who often suffer from multiple concomitant chronic disorders., Aim of the Study: This multicentre cross-sectional study was aimed at assessing the prevalence of VFs in an unselected population of patients referring to IMUs. Correlations between VFs and the main coexisting diseases were also investigated., Methods: Information on demographic, clinical and laboratory findings, and on the presence of known risk factors for osteoporosis was recorded. The Genant's semi-quantitative method was used to evaluate, in a central reading centre, the presence and severity of VFs in the thoracic and lumbar spine., Results: A cohort of 995 patients was evaluated. At least one VF of any grade was found in 47.5% of patients, with similar prevalence between females (48.1%) and males (46.7%). Older age, chronic obstructive pulmonary disease, and previous diagnosis of osteoporosis showed a significant association with VFs in multivariable analysis. However, 79.7% of the VFs were observed in patients without previous diagnosis of osteoporosis. Moreover, a VF of grade 2 or greater was found in 20.8% of patients., Conclusions: Fragility VFs is a very frequent finding in patients hospitalised in IMUs. Consequently, more attention should be devoted in this clinical setting to this comorbidity, which is known to be an additional factor for mortality and, when localised in the thoracic part of the spine, may negatively influence a concomitant respiratory insufficiency., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The primary objectives of this study on carcinomas with equivocal HER2 expression were to assess the impact of distinct recommendations with regard to identifying patients eligible for anti-HER2 agents by fluorescence in situ hybridization (FISH) and to elucidate whether multiplex ligation-dependent probe amplification (MLPA) may be of support in assessing HER2 gene status., Methods: A cohort of 957 immunohistochemistry-evaluated HER2-equivocal cases was analyzed by dual-color FISH. The results were assessed according to U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines and American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) 2007 and 2013 guidelines for dual- and single-signal in situ hybridization (ISH) assays. A subgroup of 112 cases was subjected to MLPA., Results: HER2 amplification varied from 15% (ASCO/CAP 2007 HER2/CEP17 ratio) to 29.5% (FDA/EMA HER2 copy number). According to the ASCO/CAP 2013 interpretation of the dual-signal HER2 assay, ISH-positive carcinomas accounted for 19.7%. In contrast with the ASCO/CAP 2007 ratio, this approach labeled as positive all 32 cases (3.34%) with a HER2/CEP17 ratio <2 and an average HER2 copy number ≥6.0 signals per cell. In contrast, only one case showing a HER2 copy number <4 but a ratio ≥2 was diagnosed as positive. MLPA data correlated poorly with FISH results because of the presence of heterogeneous HER2 amplification in 33.9% of all amplified carcinomas; however, MLPA ruled out HER2 amplification in 75% of ISH-evaluated HER2-equivocal carcinomas., Conclusion: The ASCO/CAP 2013 guidelines seem to improve the identification of HER2-positive carcinomas. Polymerase chain reaction-based methods such as MLPA can be of help, provided that heterogeneous amplification has been ruled out by ISH., (©AlphaMed Press.)

Background: Epileptic syndromes with continuous spikes-waves during sleep (CSWS) represent a wide spectrum of epileptic disorders having CSWS as a common EEG-feature. Defined therapeutic strategies are still lacking. We evaluated the efficacy of lacosamide add-on therapy on the EEG, behavior, and cognition in children with CSWS., Material and Methods: Eight children with CSWS refractory to other conventional antiepileptic drugs were included in the study. A 24-h EEG recording was performed at 6-month-interval in all patients. The spike-wave index (SWI) was obtained in each 24-h EEG recording. Neuropsychological data were obtained before lacosamide introduction and after a minimum of 12 months of therapy., Results: After a 6-month period of therapy, 75% of patients was defined as responder, 12.5% as partial responder and another 12.5% as non-responder. In particular, 24-h EEG normalized in 3 cases (37%). After a minimum of 12 months, 24-h EEG normalized in another patient while two patients showed electroclinical relapses. A total of 62.5% of patients was therefore defined as responder. Neuropsychological functions slightly improved in 25% of patients., Conclusion: Although further studies are needed to validate our observations, this study suggests that lacosamide add-on therapy may be safe and effective in children affected by CSWS., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Studies on the efficacy and tolerability of rufinamide in infants and young children are scarce. Here we report on an open, retrospective, and pragmatic study about safety and efficacy of rufinamide in children aged less than four years, in terms of seizures types and epilepsy syndromes., Methods: Forty children (mean age 39.5 months; range 22-48) were enrolled in the study. The mean follow-up period was 12.2 months (range 5-21). Rufinamide was initiated at a mean age of 26.7 months (range 12-42). Final rufinamide mean dosage was 31.5 mg/kg/day if associated with valproic acid and 44.2 mg/kg/day if not., Results: The highest seizure reduction rate was observed in the epileptic spasms (46%) and drop attacks (42%) groups. Seizure reduction was also observed in tonic seizures (35%) and in the focal seizure (30%) groups. In terms of epilepsy syndrome, rufinamide was effective in Lennox-Gastaut syndrome. Results were very poor for those affected by Dravet's syndrome. Globally, responder rate was 27.5%, including two (5%) patients seizure-free. Adverse reactions occurred in 37.5% of children and were mainly represented by vomiting, drowsiness, irritability, and anorexia. Discontinuation rate due to treatment-emergent adverse events was 15%., Conclusion: The present study concludes that rufinamide may be a safe and effective drug for a broad range of seizures and epilepsy syndromes in infants and young children and represents a valid therapeutic option in this population., (Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: Pallister-Killian syndrome (PKS) is a rare genetic disorder caused by a tissue-limited mosaic supernumerary isochromosome 12p. Typical facial dysmorphisms, pigmentary abnormalities, and some major malformations are frequently present. Neurological manifestations include mental retardation, hypotonia, and seizures. Epilepsy incidence ranged from 39 to 59% in a previously reported series. No specific clinical and EEG phenotype has ever been reported to describe seizure features, electroclinical patterns, and response to therapy in PKS., Methods: This was a multicentre study conducted on 13 Italian children with PKS, as diagnosed by clinical phenotype and confirmed in cultured fibroblasts. All patients underwent several polygraphic video-EEG recordings and brain magnetic resonance imaging., Results and Conclusions: All the patients presented with epilepsy and seizures that started at a mean age of 19 months. In six cases, epilepsy started with epileptic spasms (ES) combined with focal seizures in another case. In four cases, seizures were focal, and this was followed by ES in two patients. In only two cases, epilepsy started with myoclonic seizures, and spasms were never observed. The study provides further evidence that epilepsy is a part of the phenotype of PKS, although a specific clinical and EEG pattern could not be identified. Our cases show how ES with late- or first-year onset is the most common type of seizure. Despite a variable prognosis in terms of response to therapy, a significant proportion of patients achieved good seizure control., (Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

THE DORSAL COMPARTMENT OF THE FOREARM CONTAINS NINE MUSCLES: four belong to the superficial group (extensor digitorum communis, extensor digiti minimi, extensor carpi ulnaris and anconeus) and five to the deep group (supinator, abductor longus, extensor pollicis brevis, extensor pollicis longus, and extensor indices). Of these nine muscles the following details are considered: origin, course, distal insertion and their anatomical connection with those structures which are most often affected by pathologies. The radiologist must have a thorough knowledge of this complex topographic anatomy in order to perform ultrasound (US) and magnetic resonance imaging (MRI) examinations and correctly interpret the images.

Background: Atrial tachyarrhythmias (ATAs) are mainly treated by pharmacologic therapy for rate control or rhythm control. The aim of our study was to compare sotalol (S) versus beta-blocking agents (BB) in terms of prevention of ATA, cardioversions (CVs), and cardiovascular hospitalizations (H) in patients paced for bradycardia-tachycardia form of sinus node disease (BT-SND)., Methods: One hundred thirty-five patients (67 males, aged 73 +/- 7 years) were enrolled in a prospective, parallel, randomized, single-blind, multicenter study. All patients received a dual chamber rate adaptive pacemaker; after 1 month, 66 patients were randomly assigned to BB (62 +/- 26 and 104 +/- 47 mg/d for atenolol and metoprolol, respectively) and 69 patients to S (167 +/- 66 mg/d)., Results: After an observation period of 12 months, the percentage of patients free from ATA recurrences was 29% in both BB and S group. Cardioversion and H were significantly (P < .01) fewer in the 12 months after implantation than in the 12 months before both in patients treated with S (CV 69.4% vs 22.2%, H 91.7% vs 33.3%) and in patients treated with BB (CV 58.5% vs 17.1%, H 82.9% vs 26.8%). Kaplan-Meier survival analysis showed a nonsignificant trend toward a lower incidence of the composite end point (CV + H) among BB patients., Conclusions: In the complex context of "hybrid therapy" in patients with BT-SND implanted with a modern dual chamber rate adaptive pacemaker device delivering atrial antitachycardia pacing, no differences were found between the use of beta-blocker and the use of S, at the relatively low dose achieved after clinical titration, in terms of prevention of cardiovascular H or need for atrial CV.

Objectives: The aim of our study was to evaluate arterial embolism (AE) occurrence rates and predictors in patients suffering from bradycardia and wearing a pacemaker with antitachycardia pacing therapies., Background: Atrial fibrillation (AF) is associated with a high incidence of AE., Methods: A total of 725 patients (360 men, age 71 +/- 11 years) were implanted with a DDDRP pacemaker (Medtronic AT500, Medtronic Inc., Minneapolis, Minnesota). At baseline 225 (31.0%) patients received antiplatelet therapy and 264 (36.4%) patients received anticoagulation agents., Results: Over a median 22-month follow-up (25th to 75th interquartile range 16 to 30 months), AE occurred in 14 (1.9%) patients: 7 patients suffered a nonfatal ischemic stroke (0.6% per year), 4 patients had transient ischemic attack (0.34% per year), and 3 patients had embolic complications. Among baseline patients' characteristics, multivariate logistic analysis showed that embolic events are independently associated to ischemic heart disease (7.0 odds ratio [OR], 95% confidence interval [CI] 2.3 to 21.3, p = 0.001), prior embolic event (7.3 OR, 95% CI 1.2 to 43.9, p = 0.029), diabetes (5.0 OR, 95% CI 1.2 to 15.7, p = 0.032), and hypertension (4.1 OR, 95% CI 1.1 to 15.6, p = 0.036). The risk of embolism, adjusted for known risk factors, was 3.1 times increased (95% CI 1.1 to 10.5, p = 0.044) in patients with device-detected atrial fibrillation episodes longer than one day during follow-up., Conclusions: In a cohort of patients with bradycardia and AF, arterial embolism was common in patients with ischemic cardiopathy, hypertension, diabetes mellitus, and in patients with known stroke risk factors. Atrial fibrillation occurrences longer than one day were independently associated with embolic events.

Background: Emergency room (ER) evaluation of patients with acute chest pain and non-diagnostic electrocardiography (ECG) remains a frequent and difficult problem., Aim: To assess safety and prognostic implications of pharmacological stress echocardiography in the ER chest pain unit (CPU)., Methods: A total of 552 patients (321 males, age 58+/-12.6 years) with acute chest pain, negative serial enzymes and/or troponin, and ECG recordings, and normal/unchanged resting left ventricular function were prospectively enrolled and underwent pharmacological (dipyridamole or dobutamine) stress echo. Six echo labs that had passed the preliminary quality control for stress echo reading entered the study. Follow-up was obtained in all patients after a median period of 13 months., Results: No significant adverse events were observed during the test. Stress echocardiography was negative in 502 patients (91%) and positive in 50 (9%). The 502 patients with negative stress echocardiography were discharged with no or unchanged anti-ischemic medications. While the 50 patients with positive stress echo were admitted to the coronary care unit, 44 of these underwent coronary angiography with the result that 42 out of 44 showed significant coronary artery disease. There were 45 events in the follow-up: six in the 502 patients with negative and 39 in the 50 patients with positive stress echo (1.2% vs. 78%, p<0.001). The negative predictive value of stress echocardiography was 98.8% for all events and 99.6% for hard events., Conclusions: Stress echocardiography is a feasible, safe, and effective tool for early stratification of patients admitted to the ER with acute chest pain and non-ischemic ECG and resting echo.

Aim: A prospective randomized trial was set up to evaluate contractile parameters and quality of life in patients with congestive heart failure., Methods and Results: We describe the results from 38 patients in sinus rhythm and with chronic heart failure due to congestive cardiomyopathy, prospectively randomized to optimal medical therapy (Group 1, 19 patients) or optimal medical therapy plus dual chamber pacemaker programmed to optimal AV delay (Group 2, 19 patients). At a 6 month follow-up, 7/19 patients in Group 1 had died compared with 5/19 patients in Group 2. During follow-up, there were few significant changes in evaluated parameters except for mitral regurgitation time, which was prolonged in Group 1 and shortened in Group 2. The systolic left ventricular diameter shortened significantly only in Group 2. An energy and activity questionnaire showed that the effect of DDD pacing in the latter patient population was beneficial., Conclusions: From these results we may conclude that at the 6 month follow-up DDD pacing with echo-optimized AV interval programming can improve quality of life without affecting survival.