Search

BACKGROUND: There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA). OBJECTIVE: To determine the profile of biomarkers relevant to neurodegenerative disease in the CSF of patients with CAA. METHODS: We performed a detailed comparison of CSF markers, comparing patients with CAA, Alzheimer’s disease (AD), and control (CS) participants, recruited from the Biomarkers and Outcomes in CAA (BOCAA) study, and a Specialist Cognitive Disorders Service. RESULTS: We included 10 CAA, 20 AD, and 10 CS participants (mean age 68.6, 62.5, and 62.2 years, respectively). In unadjusted analyses, CAA patients had a distinctive CSF biomarker profile, with significantly lower (p

Molecular imaging techniques have rapidly progressed over recent decades providing unprecedented in vivo characterization of metabolic pathways and molecular biomarkers. Many of these new techniques have been successfully applied in the field of neuro-oncological imaging to probe tumor biology. Targeting specific signaling or metabolic pathways could help to address several unmet clinical needs that hamper the management of patients with brain tumors. This review aims to provide an overview of the recent advances in brain tumor imaging using molecular targeting with positron emission tomography and magnetic resonance imaging, as well as the role in patient management and possible therapeutic implications.

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.

BACKGROUND/AIM Systematic reporting using qualitative evaluation of PET/computed tomography (CT) results has been demonstrated to be very accurate and reproducible in posttherapy assessment of lung cancer (so-called Hopkins criteria). Our aim was to test, in a different cohort of patients, the Hopkins criteria for assessment of therapeutic response in lung cancer and to compare the results with those obtained using a semi-quantitative evaluation of uptake. METHODS This is a retrospective study. A total of 85 patients with known lung cancer who underwent fluorine-18 fluorodeoxyglucose PET/CT assessment within 24 weeks (mean 7.9 weeks) of completion of treatment were included. Treatments included surgical resection, chemotherapy, radiation therapy, immunotherapy or combinations thereof. PET/CT interpretation was done by two nuclear medicine physicians, and discrepancies were resolved by a third interpreter. Studies were scored both according to the Hopkins criteria using qualitative assessment of tracer uptake for the primary tumour, locoregional disease in the mediastinum and distant metastatic sites and by applying the same five-point score using a semi-quantitative measure, maximum standardized uptake value. Overall scores of 1, 2 and 3 were considered negative for residual disease, while scores of 4 and 5 were considered positive. Patients were followed up for a median of 18.5 months (range 2-139 months). Kaplan-Meier plots with a Mantel-Cox log-rank test were performed, considering death as the endpoint. Inter-reader variability was assessed using percent agreement and kappa statistics. RESULTS The Cohen κ coefficient analysis showed substantial agreement between the two interpreters on the five-point Hopkins criteria scoring, with a κ of 0.73. There was almost perfect agreement between the interpreters with respect to classification as positive or negative according to the Hopkins criteria, with a κ of 0.89. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the Hopkins criteria were 88.5% [95% confidence interval (CI) 80.6-96.5%), 79.2% (95% CI 63.2-95.1%), 91.5% (95% CI 84.4-98.6%), 73.1% (95% CI 61.8-84.4%) and 85.9% (95% CI 78.5-93.3%), respectively. There was almost perfect agreement between the qualitative and semi-quantitative scoring with a κ of 0.87, with sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the semi-quantitative Hopkin's criteria of 86.9% (95% CI 78.4-95.4%), 79.2% (95% CI 62.9-95.4%), 91.4% (95% CI 84.2-98.6%), 70.4% (95% CI 58.6-82.1%) and 84.7% (95% CI 80.8-92.4%), respectively. CONCLUSION The use of Hopkins criteria for posttherapy assessment in patients with lung cancer represents an easy and reproducible method with substantial to almost perfect interobserver agreement and high positive predictive value and accuracy; moreover, it is easily understood by referring physicians. Additionally, there was no significant difference when applying a semi-quantitative measure to the same five-point score.

Cerebrospinal fluid overdrainage in long-lasting shunted hydrocephalus is a well recognized complication. It may lead to different clinical syndromes which may occur over time, namely cranioencephalic disproportion and hindbrain herniation. Among the latter, Chiari malformation type 1 classically refers to one of the mildest form. When symptomatic, the patients generally exhibit a chronic, slowly progressive disease course. Although well documented in Chiari type II malformation and hydrocephalus, ventriculo-peritoneal shunt malfunction causing acute neurological deterioration in acquired Chiari malformation type 1 has been described only in three cases. All these patients underwent urgent shunt revision and suboccipital decompression in two of them, achieving good clinical improvement. We report on a 20-year-old woman harboring a previously asymptomatic Chiari malformation type 1, who experienced an acute foramen magnum syndrome with ventriculo-peritoneal shunt malfunction. We performed an endoscopic third-ventriculo-cisternostomy and definite removal of the shunt, obtaining the complete resolution of symptoms and shunt independence at 2 years follow-up. The phisiopathogenetic mechanisms and surgical management are discussed.

Background Transperineal laser ablation (TPLA) of the prostate is a novel, mini-invasive option for men with lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH). Our aim was to assess the impact of ultrasound-guided TPLA regarding urodynamic improvement and sexual function, monitoring clinical data, postprocedural complications and imaging findings at 3-T multiparametric magnetic resonance imaging. Methods Forty-four patients aged ≥ 50 affected with moderate to severe LUTS (International Prostate Symptoms score ≥ 12) due to benign prostatic obstruction and refractoriness, intolerance or poor compliance to medical therapies underwent US-guided TPLA between May 2018 and February 2020. Clinical measurements included PSA, uroflowmetry, sexual function assessment (using the International Index of Erectile Function and Male Sexual Health Questionnaire-Ejaculatory Dysfunction short form) and quality of life questionnaire. Adverse events were evaluated using the Clavien-Dindo scale. Volume changes were measured by MRI and automatic segmentation software during 1-year follow-up. Registration: NCT04044573 – May 5th, 2018, https://www.clinicaltrials.gov Results MRI assessed the changes over time with a 53% mean reduction of adenoma volume and 71% of the ablated area, associated with clinical and functional improvement and resolution of LUTS in all cases. Five of 44 patients (11.3%) had urinary blockage due to clots and required re-catheterisation for 2 weeks. The overall adverse event rate was 7%. Conclusion US-guided TPLA performed as a safe, manageable and effective treatment for LUTS. It could be considered an alternative effective mini-invasive procedure to standard treatments for BPH in the outpatient setting.

INTRODUCTION AND OBJECTIVE:Ureteral injuries are well-known complications of abdominal surgery. The aim of the study is to evaluate the safety and feasibility of Allium ureteral prosthesis in patie...

Background Cauda equina syndrome (CES) is a challenging condition and it can be caused by variable entities. Leptomeningeal carcinomatosis (LC) is a multifocal seeding of the leptomeninges by malignant cells and it is observed in 1-8% of patients with solid tumors. Diagnosis of intradural metastases of the cauda equina is often delayed due to the non-specific characteristics of this condition but also to the delay of presentation of many patients. Cauda equina metastases usually occur in advanced cancers, but rarely can be the first presentation of disease. Case description A 63-year-old man presented with 6 months history of low back pain and 20 d history of bilateral sciatica, hypoesthesia of the legs and the saddle, flaccid paraparesis and bowel incontinence determine by multiple nodular small lesions on the entire cauda equina with contrast-enhancement. Total-body CT showed a millimetric lesion at the lung. The patient underwent L2-L5 laminectomy and subtotal removal and histological examination showed a small cell lung carcinoma metastasis. Conclusions In the literature, 54 cases of CES from non-CNS tumor metastasis are described. The diagnosis is challenging, back pain, with or without irradiation to the lower limbs, is the most frequently reported disturbance. In about 30% of patients there is no known malignancy and CES is the first clinical presentation. Treatment of choice is surgery, followed by radiotherapy and less frequently adjuvant chemotherapy. The surgical removal is almost always incomplete and functional outcome is often not satisfactory. Prognosis is poor.

Surgery is the curative treatment of choice in many types of cancer diagnosed at an early stage when the disease is still localized, and there is no evidence of distant metastases. The success of curative surgery depends on removing the tumor with a margin of healthy tissue around it to ensure that no malignant cells are left behind. However, the recurrence rates after complete surgical resection with curative intent remain high in many types of cancer. Imaging plays an essential role in the assessment of postoperative complications. The chapter will discuss the advantages and limitations of conventional imaging and PET/CT in the postsurgical setting of various cancer types, reviewing several guidelines and recommendations. Besides, the potential pitfalls in the image interpretation will be discussed.

Purpose This study assesses the potential for vascular-metabolic imaging with FluoroDeoxyGlucose (FDG)–Positron Emission Tomography/Computed Tomography (PET/CT) perfusion to provide markers of prognosis specific to the site and stage of colorectal cancer. Methods This prospective observational study comprised of participants with suspected colorectal cancer categorized as either (a) non-metastatic colon cancer (M0colon), (b) non-metastatic rectal cancer (M0rectum), or (c) metastatic colorectal cancer (M+). Combined FDG-PET/CT perfusion imaging was successfully performed in 286 participants (184 males, 102 females, age: 69.60 ± 10 years) deriving vascular and metabolic imaging parameters. Vascular and metabolic imaging parameters alone and in combination were investigated with respect to overall survival. Results A vascular-metabolic signature that was significantly associated with poorer survival was identified for each patient group: M0colon – high Total Lesion Glycolysis (TLG) with increased Permeability Surface Area Product/Blood Flow (PS/BF), Hazard Ratio (HR) 3.472 (95% CI: 1.441–8.333), p = 0.006; M0rectum – high Metabolic Tumour Volume (MTV) with increased PS/BF, HR 4.567 (95% CI: 1.901–10.970), p = 0.001; M+ participants, high MTV with longer Time To Peak (TTP) enhancement, HR 2.421 (95% CI: 1.162–5.045), p = 0.018. In participants with stage 2 colon cancer as well as those with stage 3 rectal cancer, the vascular-metabolic signature could stratify the prognosis of these participants. Conclusion Vascular and metabolic imaging using FDG-PET/CT can be used to synergise prognostic markers. The hazard ratios suggest that the technique may have clinical utility.

PET holds potential to provide additional information about tumour metabolic processes, which could aid brain tumour differential diagnosis, grading, molecular subtyping and/or the distinction of therapy effects from disease recurrence. This review discusses PET techniques currently in use for untreated and treated glioma characterization and aims to critically assess the evidence for different tracers ([F]Fluorodeoxyglucose, choline and amino acid tracers) in this context.

Many therapies are available for trigeminal neuralgia (TN), from medical therapy to invasive, mininvasive and non-invasive methods. There is no a unique indication concerning the choice of treatment; we report our indications for gasserian ganglion compression with balloon by percutaneous approach. Out of 421 patients affected by TN treated with various methods from 2004 through to 2014, we present 46 patients treated by gasserian ganglion compression with balloon catheter. Patients selected for this procedure were only those refractory to medical therapy and refractory to the other available therapies (radiofrequency, microvascular decompression, radiosurgery, glycerolization, peripheral alcoholizations): balloon compression was performed as third line therapy. After the procedure, twenty-eight patients were classified as BNI pain intensity score grade 1, seven other as grade 2, three other as grade 3, six were classified as BNI grade 4, and in one patient no improvement of pain occurred (BNI grade 5). After an average period of follow up of 8,6 years, four cases of pain recurrence occurred. Because balloon compression is an ablative and non-selective procedure and all three trigeminal divisions are damaged to achieve stable pain remission, the procedure was performed only in patients affected by recurrent TN refractory to the other available methods.

WOS: 000450412900002 PubMed ID: 30312790 We hypothesized that dopamine neuromodulation might affect cortical excitability in Parkinson's disease (PD) patients set in quiet wakefulness, as revealed by resting state eyes-closed electroencephalographic (rsEEG) rhythms at alpha frequencies (8-12 Hz). Clinical and rsEEG rhythms in PD with dementia (N = 35), PD with mild cognitive impairment (N = 50), PD with normal cognition (N = 35), and normal (N = 50) older adults were available from an international archive. Cortical rsEEG sources were estimated by exact low-resolution brain electromagnetic tomography. Compared with the normal older group, the PD groups showed reduced occipital alpha sources and increased widespread delta (

Background: The reasons behind low adherence to the Mediterranean diet (Med-diet) are still not entirely known. We aimed to evaluate the effect of biological (i.e., sex-related) and psycho-socio-cultural (i.e., gender-related) factors on Med-diet adherence. Methods: Baseline Med-diet adherence was measured using a self-administered questionnaire among adults with ischemic heart disease (IHD) from the EVA (Endocrine Vascular Disease Approach) study. A multivariable analysis was performed to estimate the effect of sex- and gender-related factors (i.e., identity, roles, relations, and institutionalized gender) on low adherence. Results: Among 366 participants (66 ± 11 years, 31% women), 81 (22%) adults with low adherence demonstrated higher rates of diabetes, no smoking habit, lower male BSRI (Bem Sex Role Inventory) (median (IQR) 4.8 (4.1 to 5.5) vs. 5.1 (4.5 to 5.6) and p = 0.048), and higher Perceived Stress Scale 10 items (PSS-10) (median (IQR) 19 (11 to 23) vs. 15 (11 to 20) and p = 0.07) scores than those with medium-high adherence. In the multivariable analysis, only active smoking (odds ratio, OR = 2.10, 95% confidence interval, CI 1.14 to 3.85 and p = 0.017), PPS-10 (OR = 1.04, 95% CI 1.00 to 1.08, and p = 0.038) and male BSRI scores (OR = 0.70, 95% CI 0.52 to 0.95, and p = 0.021) were independently associated with low adherence. Conclusions: Male personality traits and perceived stress (i.e., gender identity) were associated with low Med-diet adherence regardless of the sex, age, and comorbidities. Therefore, gender-sensitive interventions should be explored to improve adherence in IHD.

AIMS Experimental data suggest that visceral adipose tissue (VAT) dysfunction contributes to non-alcoholic fatty liver disease (NAFLD) development in obesity, however, data on humans are limited. Aims of this study were to investigate the relationship between NAFLD and VAT morphofunctional impairment and to determine whether the extent of VAT remodelling is associated with liver damage and metabolic alterations in obesity. METHODS We analysed data from 40 obese individuals candidate to bariatric surgery in whom paired intraoperative liver and omental biopsies were performed for diagnosing NAFLD and VAT inflammation by immunohistochemistry and mRNA expression studies. RESULTS Within our study population, NAFLD was significantly associated with greater VAT CD68+ macrophages infiltration (P = .04), fibrosis (P = .04) and impaired microvascular density (P = .03) as well as increased expression of markers of local hypoxia, apoptosis and inflammation (UNC5B, CASP7, HIF1-α, IL-8, MIP2, WISP-1, all P

INTRODUCTION: To investigate the combined performance of quantitative CT (qCT) following a computer algorithm analysis (IMBIO) and 18F-FDG PET/CT to assess survival in patients with idiopathic pulmonary fibrosis (IPF). METHODS: A total of 113 IPF patients (age 70 ± 9 years) prospectively and consecutively underwent 18F-FDG PET/CT and high-resolution CT (HRCT) at our institution. During a mean follow-up of 29.6 ± 26 months, 44 (48%) patients died. As part of the qCT analysis, pattern evaluation of HRCT (using IMBIO software) included the total extent (percentage) of the following features: normal-appearing lung, hyperlucent lung, parenchymal damage (comprising ground-glass opacification, reticular pattern and honeycombing), and the pulmonary vessels. The maximum (SUVmax) and minimum (SUVmin) standardized uptake value (SUV) for 18F-FDG uptake in the lungs, and the target-to-background (SUVmax/SUVmin) ratio (TBR) were quantified using routine region-of-interest (ROI) analysis. Pulmonary functional tests (PFTs) were acquired within 14 days of the PET/CT/HRCT scan. Kaplan-Meier (KM) survival analysis was used to identify associations with mortality. RESULTS: Data from 91 patients were available for comparative analysis. The average ± SD GAP [gender, age, physiology] score was 4.2 ± 1.7 (range 0-8). The average ± SD SUVmax, SUVmin, and TBR were 3.4 ± 1.4, 0.7 ± 0.2, and 5.6 ± 2.8, respectively. In all patients, qCT analysis demonstrated a predominantly reticular lung pattern (14.9 ± 12.4%). KM analysis showed that TBR (p = 0.018) and parenchymal damage assessed by qCT (p = 0.0002) were the best predictors of survival. Adding TBR and qCT to the GAP score significantly increased the ability to differentiate between high and low risk (p < 0.0001). CONCLUSION: 18F-FDG PET and qCT are independent and synergistic in predicting mortality in patients with IPF.

Hydrocephalus and ex-vacuo ventricular dilatations which cause persistent brain herniation with impossibility to perform cranioplasty, are well known late complications after decompressive hemicraniectomy; concerning the physiopathologic mechanism leading to these complications, there are several theories. We report the particular case of a patient suffering from persistent brain herniation after decompressive hemicraniectomy, due to development of subdural hygroma, intraparenchymal multiple liquoral cysts and only mild enlargement of frontal horn of right lateral ventricle. A fifty-five years old male patient was treated with decompressive right hemicraniectomy for acute hemispheric swelling consequent to right internal carotid artery dissecation. After several months, evaluating the patient for cranioplasty, brain herniation was clinically evident and brain MRI confirmed it due to subdural hygroma, intraparenchymal multiple liquoral cysts and mild enlargement of frontal horn of right lateral ventricle. According to several reported theories, communication between right frontal horn of lateral ventricle, intraparenchymal liquoral cysts and subdural hygroma was supposed, and CSF lumbar drainage was placed. Regression of brain herniation was achieved and cranioplasty was possible; after few days lumbar drainage was removed: neither operative, nor short and long follow-up period complications were observed. Temporary CSF lumbar drainage resulted effective to obtain regression of a particular case of persistent brain herniation developed after decompressive hemicraniectomy; moreover this safe procedure, not previously described to forerun cranioplasty surgery to our knowledge, allowed performing cranioplasty in absence of complications and avoiding temporary or permanent ventricular shunts which present a major rate of risks and possible complications.

Gliomas are the most common primary brain tumours in children and adults, consisting of a heterogeneous group of neoplastic diseases arise from the supporting cells of the CNS (glial cells). Their histopathological and molecular characteristics vary considerably as do their management and prognosis. Conventional gadolinium-enhanced magnetic resonance imaging (MRI) is considered the primary imaging modality for initial work up and follow up of patients with gliomas, although it has some limitations, especially in differentiating high from low grade tumours and in distinguishing disease recurrence from post-therapy changes. Hybrid positron emission tomography (PET)/MRI is a relatively novel tool that combines MRI sequences with metabolic information from PET, and therefore different PET radiotracers, in a single scan. This article discusses the main advantages and disadvantages of combined PET/MRI compared to other conventional or more widely available imaging tools, such as MRI or combined positron emission tomography–computed tomography. The main uses of PET/MRI and the most commonly used PET radiotracers in providing diagnostic, prognostic and predictive information in patients with glioma are covered.

WOS: 000424245200019 PubMed ID: 29439335 The present study tested the hypothesis that cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms reveal different abnormalities in cortical neural synchronization in groups of patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) and dementia with Lewy bodies (DLBMCI) as compared to cognitively normal elderly (Nold) subjects. Clinical and rsEEG data in 30 ADMCI, 23 DLBMCI, and 30 Nold subjects were available in an international archive. Age, gender, and education were carefully matched in the three groups. The Mini-Mental State Evaluation (MMSE) score was matched between the ADMCI and DLBMCI groups. Individual alpha frequency peak (IAF) was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were also considered. eLORETA estimated the rsEEG cortical sources. Receiver operating characteristic curve (ROCC) classified these sources across individuals. Compared to Nold, IAF showed marked slowing in DLBMCI and moderate in ADMCI. Furthermore, the posterior alpha 2 and alpha 3 source activities were more abnormal in the ADMCI than the DLBMCI group, while widespread delta source activities were more abnormal in the DLBMCI than the ADMCI group. The posterior delta and alpha sources correlated with the MMSE score and correctly classified the Nold and MCI individuals (area under the ROCC > 0.85). In conclusion, the ADMCI and DLBMCI patients showed different features of cortical neural synchronization at delta and alpha frequencies underpinning brain arousal and vigilance in the quiet wakefulness. Future prospective cross-validation studies will have to test the clinical validity of these rsEEG markers. H2020 Marie S. Curie ITN-ETN project The present study was developed based on the data of the informal European Consortium PDWAVES and European Consortium of Dementia with Lewy Bodies. The members and institutional affiliations of the Consortia are reported in the cover page of this manuscript. The research activities of the Unit of University of Rome "La Sapienza" were partially supported by the H2020 Marie S. Curie ITN-ETN project with the short title "BBDiag" (http://bbdiag-itn-etn.eu). We thank Mrs. Jessica Janson and Mrs. Marina Selivanova for their support to those activities in the framework of the BBDiag project.

WOS: 000428233700003 PubMed ID: 29407464 Previous evidence showed abnormal posterior sources of resting-state delta (< 4 Hz) and alpha (8-12 Hz) rhythms in patients with Alzheimer's disease with dementia (ADD), Parkinson's disease with dementia (PDD), and Lewy body dementia (DLB), as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis of additional abnormalities in functional cortical connectivity computed in those sources, in ADD, considered as a "disconnection cortical syndrome", in comparison with PDD and DLB. Resting-state eyes-closed electroencephalographic (rsEEG) rhythms had been collected in 42 ADD, 42 PDD, 34 DLB, and 40 normal healthy older (Hold) participants. Exact low-resolution brain electromagnetic tomography (eLORETA) freeware estimated the functional lagged linear connectivity (LLC) from rsEEG cortical sources in delta, theta, alpha, beta, and gamma bands. The area under receiver operating characteristic (AUROC) curve indexed the classification accuracy between Nold and diseased individuals (only values > 0.7 were considered). Interhemispheric and intrahemispheric LLCs in widespread delta sources were abnormally higher in the ADD group and, unexpectedly, normal in DLB and PDD groups. Intrahemispheric LLC was reduced in widespread alpha sources dramatically in ADD, markedly in DLB, and moderately in PDD group. Furthermore, the interhemispheric LLC in widespread alpha sources showed lower values in ADD and DLB than PDD groups. At the individual level, AUROC curves of LLC in alpha sources exhibited better classification accuracies for the discrimination of ADD versus Nold individuals (0.84) than for DLB versus Nold participants (0.78) and PDD versus Nold participants (0.75). Functional cortical connectivity markers in delta and alpha sources suggest a more compromised neurophysiological reserve in ADD than DLB, at both group and individual levels. (C) 2017 Elsevier Inc. All rights reserved. H2020 Marie S. Curie ITN-ETN project The present study was developed based on the data of the informal European Consortium PDWAVES and European Consortium of Dementia with Lewy Body. The members and institutional affiliations of the consortia are reported in the cover page of this manuscript. The research activities of the Unit of University of Rome "La Sapienza" were partially supported by the H2020 Marie S. Curie ITN-ETN project with the short title "BBDiag" (http://bddiag-itn-etn.eu). We thank Mrs. Jessica Janson and Mrs. Marina Selivanova for their support to those activities in the framework of the BBDiag project.

WOS: 000427485900009 PubMed ID: 29448151 Objective: This study tested the hypothesis that markers of functional cortical source connectivity of resting state eyes-closed electroencephalographic (rsEEG) rhythms may be abnormal in subjects with mild cognitive impairment due to Alzheimer's (ADMCI) and Parkinson's (PDMCI) diseases compared to healthy elderly subjects (Nold). Methods: rsEEG data had been collected in ADMCI, PDMCI, and Nold subjects (N = 75 for any group). eLORETA freeware estimated functional lagged linear connectivity (LLC) from rsEEG cortical sources. Area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification of Nold and MCI individuals. Results: Posterior interhemispheric and widespread intrahemispheric alpha LLC solutions were abnormally lower in both MCI groups compared to the Nold group. At the individual level, AUROC curves of LLC solutions in posterior alpha sources exhibited moderate accuracies (0.70-0.72) in the discrimination of Nold vs. ADMCI-PDMCI individuals. No differences in the LLC solutions were found between the two MCI groups. Conclusions: These findings unveil similar abnormalities in functional cortical connectivity estimated in widespread alpha sources in ADMCI and PDMCI. This was true at both group and individual levels. Significance: The similar abnormality of alpha source connectivity in ADMCI and PDMCI subjects might reflect common cholinergic impairment. (C) 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved. H Marie S. Curie ITN-ETN project The present study was developed based on the data of the informal European Consortium PDWAVES and European Consortium of Dementia with Lewy Body. The members and institutional affiliations of the Consortia are reported in the cover page of this manuscript. Dr. Erol Basar passed away due to health problems on October 28th (November 18th 1938-October 28th 2017) in Istanbul, during the editorial processing of this manuscript. Until the end of his life, he had been working to the development of EEG science and its application in Clinical Neurophysiology. He leaves to all us an invaluable scientific legacy in the Science of Brain Rhythms and Human Cognition. He also leaves a permanent reminder of scientific passion, academic soul, and social responsibility to all fortunate people who met and knew him during his intense life. The research activities of the Unit of University of Rome "La Sapienza" were partially supported by the H2020 Marie S. Curie ITN-ETN project with the short title "BBDiag" (http://bbdiag-ITNetn.eu). We thank Mrs. Jessica Janson and Mrs. Marina Selivanova for their support to those activities in the framework of the BBDiag project.

PURPOSE: There is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of 18F-FDG-PET/ CT to predict mortality in IPF. METHODS: A total of 113 IPF patients (93 males, 20 females, mean age ± SD: 70 ± 9 years) were prospectively recruited for 18F-FDG-PET/CT. The overall maximum pulmonary uptake of 18F-FDG (SUVmax), the minimum pulmonary uptake or background lung activity (SUVmin), and target-to-background (SUVmax/ SUVmin) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan-Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary 18F-FDG-PET measurements and GAP score for risk stratification in IPF patients. RESULTS: During a mean follow-up of 29 months, there were 54 deaths. The mean TBR ± SD was 5.6 ± 2.7. Mortality was associated with high pulmonary TBR (p = 0.009), low forced vital capacity (FVC; p = 0.001), low transfer factor (TLCO; p < 0.001), high GAP index (p = 0.003), and high GAP stage (p = 0.003). Stepwise forward-Wald-Cox analysis revealed that the pulmonary TBR was independent of GAP classification (p = 0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR > 4.9 was 24 months. Combining PET data with GAP data ("PET modified GAP score") refined the ability to predict mortality. CONCLUSIONS: A high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.

Adipose tissue (AT) inflammation leads to increased free fatty acid (FFA) efflux and ectopic fat deposition, but whether AT dysfunction drives selective fat accumulation in specific sites remains unknown. The aim of the present study was to investigate the correlation between AT dysfunction, hepatic/pancreatic fat fraction (HFF, PFF) and the associated metabolic phenotype in patients with Type 2 diabetes (T2D). Sixty-five consecutive T2D patients were recruited at the Diabetes Centre of Sapienza University, Rome, Italy. The study population underwent clinical examination and blood sampling for routine biochemistry and calculation of insulin secretion [homoeostasis model assessment of insulin secretion (HOMA-β%)] and insulin-resistance [homoeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance (ADIPO-IR)] indexes. Subcutaneous (SAT) and visceral (VAT) AT area, HFF and PFF were determined by magnetic resonance. Some 55.4% of T2D patients had non-alcoholic fatty liver disease (NAFLD); they were significantly younger and more insulin-resistant than non-NAFLD subjects. ADIPO-IR was the main determinant of HFF independently of age, sex, HOMA-IR, VAT, SAT and predicted severe NAFLD with the area under the receiver operating characteristic curve (AUROC)=0.796 (95% confidence interval: 0.65–0.94, P=0.001). PFF was independently associated with increased total adiposity but did not correlate with AT dysfunction, insulin resistance and secretion or NAFLD. The ADIPO-IR index was capable of predicting NAFLD independently of all confounders, whereas it did not seem to be related to intrapancreatic fat deposition; unlike HFF, higher PFF was not associated with relevant alterations in the metabolic profile. In conclusion, the presence and severity of AT dysfunction may drive ectopic fat accumulation towards specific targets, such as VAT and liver, therefore evaluation of AT dysfunction may contribute to the identification of different risk profiles among T2D patients.

In BRAF-mutant (BRAF-mut) melanoma combined BRAF/MEK inhibition increases survival. However, pharmacological effects on the genetically “normal” tumor microenvironment (i.e. paradox MAPK activation) may set the stage for the development of drug resistance. In melanoma specimens, we observed a significant correlation between BRAF-mut and the expression of Semaphorin 6A (Sema6A), a member of the semaphorin family that regulates actin cytoskeleton remodeling, motility and cell proliferation. In BRAF-mut melanoma cell lines, Sema6A is involved in cytoskeleton remodeling by regulation of YAP activity. Sema6A depletion induced a decrease in RhoA activation and, consequently, an increase in phospho-YAP and a reduction in cell proliferation rate. We thus hypothesized that actin cytoskeleton remodeling and dynamic evolutions may play a role in both cell autonomous and stroma-mediated mechanisms of drug-resistance in this context. To assess the functional relevance of Sema6A expression in the regulation of melanoma/stroma interactions and sensitivity/resistance to pathway inhibitors, we performed an inducible Sema6A knock down in BRAF-mut melanoma cell lines and evaluated the response to BRAF/MEK inhibitors in monolayer and 2D co-culture systems. In contexts of partial response or resistance in vitro, BRAF inhibitors, alone or combined with MEK inhibitors, were increased Sema6A expression at the mRNA and protein levels in both monolayer and 2D co-culture systems. Furthermore, Sema6A silencing performed in 2D co-culture system abrogated the protective effect of melanoma/stroma interactions, resulting in a synergistic effect with BRAF/MEK inhibitors. Overall, our results suggest that Sema6A could be a crucial mediator of protective tumor/stroma interactions, involved in resistance to MAPK inhibition in melanoma. Citation Format: Rossella Loria, Italia Falcone, Marta Di Martile, Valentina Caprara, Rocco Fraioli, Valentina Laquintana, Giulia Bon, Laura Rosanò, Donatella Del Bufalo, Ludovica Ciuffreda, Virginia Ferraresi, Michele Milella, Rita Falcioni. Tumor-stroma interactions mediated by Semaphorin 6A as a determinant of drug resistance in BRAF-mut melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1887.

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated. Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD. Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence. Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99). Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner.

Gliomas account for 80% of all intrinsic primary brain tumours, including several subtypes with different prognoses [1]. Histological characterisation following the World Health Organisation (WHO) groups gliomas on cell origin (astrocytoma, oligodendroglioma), with assessment of pathological features of malignancy. Low-grade gliomas (LGG, WHO grades I–II) show a better prognosis than high-grade gliomas (HGG, WHO grade III–IV) [2].

Osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC) are matrix glycoproteins which mediate bone mineralization; moreover, their effects on glucose/insulin homeostasis have recently been demonstrated. Higher circulating OPN and OPG levels have been associated with the presence of insulin resistance, atherosclerosis and coronary heart disease. No data are available on contextual changes of these markers in type 2 diabetes mellitus (T2DM). Therefore, aims of this study were to evaluate serum OPN, OPG and OC levels in T2DM patients and their clinical correlates. We recruited 83 consecutive T2DM patients referring to our diabetes outpatient clinics at Sapienza, University of Rome, and 71 non-diabetic sex and age-comparable subjects as a control group. Study population underwent metabolic characterization and carotid ultrasound for intima–media thickness measurement. Plasma OPN, OPG and OC were measured by MILLIPLEX Multiplex Assays Luminex. T2DM patients had significantly higher circulating OPN and OPG levels than controls (14.3 ± 13.6 vs 10.6 ± 13.7 ng/ml p

The major challenge in pre-surgical epileptic patient evaluation is the correct identification of the seizure onset area, especially in MR-negative patients. In this study, we aimed to: (1) assess the concordance between perfusion, from ASL, and metabolism, from 18F-FDG, acquired simultaneously on PET/MR; (2) verify the utility of a statistical approach as supportive diagnostic tool for clinical readers. Secondarily, we compared 18F-FDG PET data from the hybrid PET/MR system with those acquired with PET/CT, with the purpose of validate the reliability of 18F-FDG PET/MR data. Twenty patients with refractory focal epilepsy, negative MR and a defined electro-clinical diagnosis underwent PET/MR, immediately followed by PET/CT. Standardized uptake value ratio (SUVr) and cerebral blood flow (CBF) maps were calculated for PET/CT-PET/MR and ASL, respectively. For all techniques, z-score of the asymmetry index (zAI) was applied for depicting significant Right/Left differences. SUVr and CBF images were firstly visually assessed by two neuroimaging readers, who then re-assessed them considering zAI for reaching a final diagnosis. High agreement between 18F-FDG PET/MR and ASL was found, showing hypometabolism and hypoperfusion in the same hemisphere in 18/20 patients, while the remaining were normal. They were completely concordant in 14/18, concordant in at least one lobe in the remaining. zAI maps improved readers' confidence in 12/20 and 15/20 patients for 18F-FDG PET/MR and ASL, respectively. 18F-FDG PET/CT-PET/MR showed high agreement, especially when zAI was considered. The simultaneous metabolism-perfusion acquisition provides excellent concordance on focus lateralisation and good concordance on localisation, determining useful complementary information., Highlights • Simultaneous PET/MR to evaluate cerebral perfusion and glucose metabolism in MR-negative refractory focal epilepsy patients. • ASL and 18F-FDG PET/MR showed excellent concordance on lateralisation and good concordance on localisation of focus. • ASL and 18F-FDG PET/MR can provide complementary information for focus localisation. • An individually-tailored z-score approach can allow a better identification of the epileptic focus.

Objectives To propose a risk score predicting the potential occurrence of procedure-related complications in patients undergoing computed tomography (CT)-guided lung biopsy. Methods Institution review board approval was obtained. A total of 342 CT-guided lung biopsies were retrospectively evaluated taking into account procedure-related complications and associated risk factors, including patient gender and age, previous radiation therapy (RT) and/or chemotherapy (CHT), lesion size, depth and location, incomplete pulmonary fissures, associated diffuse lung diseases, previous pneumothorax (PNX), lung volumes, punctured fissures, thoracic access, needle size and operator experience. Complications were assessed on chest X-ray and/or CT scans. Stepwise logistic regression was used to identify risk factors, to evaluate their correlation with procedure-related complications and to calculate models of risk (MoRs). Results PNX requiring chest tube placement occurred in 39 patients (11.4%), high-grade pulmonary parenchymal haemorrhage occurred in 62 patients (18.1%) and haemothorax occurred in 12 patients (3.5%). Risk factors increasing the incidence of complications were lesion size (P = 0.01), lesion depth (P = 0.01) and incomplete pulmonary fissures (P = 0.01); previous chemo-radiation therapy was correlated to a lower incidence of complications (P = 0.01). MoR for PNX was as follows: risk base line = 60%; age = +0.15%/year; punctured fissures = +20%; incomplete fissures = +9%; previous CHT/RT = -10%. MoR for parenchymal haemorrhage was as follows: risk base line = 20%, lesion depth = +0.8%/mm; age = +0.25%/year; incomplete fissures = +15%. MoR for haemothorax was as follows: risk base line = 1%; previous PNX = +20%; incomplete fissures = 7%; both previous PNX and incomplete fissures = +67%. Conclusion This study provides MoRs to predict the risk of complications in patients undergoing CT-guided percutaneous lung biopsies.

Medical therapy with dopamine agonist is very effective in controlling prolactin serum levels and it usually represents the first therapeutic choice for prolactin secreting pituitary adenomas. However, many patients present increase of prolactinemia after withdrawal of medical therapy which consequently should be taken for long time; other present intolerance to medical therapy; women with pregnancy need to withdraw dopamine agonists with consequent potential related problems: in these patients transsphenoidal surgery can be requested. The presented study concerns the efficacy of transsphenoidal surgery in patients affected by microprolactinoma after treatment with medical therapy for different periods of time. Different postsurgical results were achieved in 2 groups of 24 (group 1) and 25 (group 2) patients affected by microprolactinoma who had taken medical therapy for a period of time respectively longer or shorter than 1 year. In summary, the authors observed in group 1 a rate of hormonal remission of 33.3% and an overall prolactinemia improvement with possibility of medical therapy withdrawal in 49.9% of patients. In group 2, the authors observed a rate of hormonal remission of 84% and an overall rate of improvement with no necessity of medical therapy of 92%. Therefore, the authors' experience showed that the surgical option for the therapy of microprolactinomas should be indicated within 1 year from the beginning of medical therapy with dopamine agonist, to achieve a high rate of hormonal remission and possibility to withdraw medical therapy. The authors' protocol for microprolactinoma treatment is presented.

Background Patients affected by tuberous sclerosis (TS) have a greater incidence of tumors than the healthy population. Spinal tumours in TS are reported very rarely and consist mainly of sacrococcygeal and cervical chordomas. Method Case report. Findings A 21-year-old man, affected by TS, presented a spinal dorsal T2 tumor that caused medullary compression. He underwent decompressive laminectomy and microsurgical excision of a giant cell tumor and an associated aneurysmal bone cyst. Postoperative hypofractionated radiotherapy was performed on the surgical field. At 2.4 years of follow-up the patient reported total recovery of neurological deficits and was free from tumor recurrence. Conclusion Considering this association, which is the first reported in the literature, spinal magnetic resonance imaging with gadolinium should be performed at the onset of spinal pain in patients affected by TS.

Purpose: To determine whether wide-volume perfusion computed tomography (CT) performed with a new generation scanner can allow evaluation of the effects of chemotherapy combined with antiangiogenetic treatment on the whole tumor mass in patients with locally advanced lung adenocarcinoma and to determine if changes in CT numbers correlate with the response to therapy as assessed by conventional response evaluation criteria in solid tumors (RECIST) Materials and Methods: Forty-five patients with unresectable lung adenocarcinoma underwent perfusion CT before and 40 and 90 days after chemotherapy and antiangiogenetic treatment. RECIST measurements and calculations of blood flow, blood volume, time to peak, and permeability were performed by two independent blinded radiologists. Pearson correlation coefficient was used to assess the correlation between baseline CT numbers. Baseline and follow-up perfusion parameters of the neoplastic lesions were tested overall for statistically significant differences by using the repeatedmeasures analysis of variance and then were also compared on the basis of the therapy response assessed according to the RECIST criteria. Results: Pearson correlation coefficient showed a significant correlation between baseline values of blood flow and blood volume ( ρ = 0.48; P = 001), time to peak and permeability ( ρ = 0.31; P = 04), time to peak and blood flow ( ρ = - 0.66; P < 001), and time to peak and blood volume ( ρ = - 0.39; P = 007). Blood flow, blood volume, and permeability values were higher in responding patients than in the other patients, with a significant difference at second follow-up for blood flow ( P = 0001), blood volume ( P = 02), and permeability ( P = 0001); time to peak was higher in nonresponding patients ( P = 012). Conclusion: Perfusion CT imaging may allow evaluation of lung cancer angiogenesis demonstrating alterations in vascularity following treatment. © RSNA, 2011.

Purpose: This study was done to assess the diagnostic potential of dual-source computed tomography (DSCT) in the functional evaluation of lung cancer patients undergoing surgical resection. The CT data were compared with pulmonary perfusion scintigraphy and pulmonary function tests (PFTs). Materials and methods: All patients were evaluated with DSCT, scintigraphy and PFTs. The DSCT scan protocol was as follows: two tubes (80 and 140 kV; Care Dose protocol); 70 cc of contrast material (5 cc/s); 5- to 6-s scan time; 0.6 mm collimation. After the automatic calculation of lung perfusion with DSCT and quantification of air volumes and emphysema with dedicated software applications, the perfusional CT studies were compared with scintigraphy using a visual score for perfusion defects; CT air volumes and emphysema were compared with PFTs. Results: The values of accuracy, sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of DSCT compared with perfusion scintigraphy as the reference standard were: 0.88, 0.84, 0.90, 0.93 and 0.88, respectively. The McNemar test did not identify significant differences either between the two imaging techniques (p=0.07) or between CT and PFTs (p=0.09). Conclusions: DSCT is a robust and promising technique that provides important and accurate information on lung function. © 2011 Springer-Verlag Italia.

Background. Osteoarthritis (OA) is the most common musculoskeletal disease in the world. OA is the result of an inflammatory and degenerative process affecting the entire joint. Osteoarthritis, especially involving the knee, has a relevant socioeconomic impact in terms of drugs, hospital admissions, work absences, and temporary or permanent invalidity. Therapy of knee osteoarthritis is based on pharmacological and nonpharmacological measures.Methods. We conducted a systematic review of the studies published between 2002 and 2017 on spa therapy, mud-pack therapy, balneotherapy, and mud-bath therapy in the treatment of knee osteoarthritis in order to investigate the evidence of the efficacy of such treatment on pain, functional limitation, drug use, and quality of life. Overall, 35 studies were examined among which 12 were selected and included in the review if they are trial comparative. We have been able to illustrate the main results obtained in the individual studies and to elaborate these results in order to allow as much a unitary presentation as possible and hence an overall judgment.Results. Because the studies we reviewed differed markedly from one another in terms of the methods used, we were unable to conduct a quantitative analysis (meta-analysis) of pooled data from the 12 studies. For the purposes of the present review, we reevaluated the results of the different studies using the same statistical method, Student’st-test, which is used to compare the means of two frequency distributions. Among all the studies, the most relevant indexes used to measure effectiveness of spa therapy were improved including VAS, Lequesne, and WOMAC Score.Conclusions. The mud-pack therapy, balneotherapy, mud-bath therapy, and spa therapy have proved to be effective in the treatment and in the secondary prevention of knee osteoarthritis, by reducing pain, nonsteroidal anti-inflammatory drug consumption, and functional limitation and improving quality of life of affected patients.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

Background: Spinal cord metastasis is an uncommon event in glioblastoma, symptomatic lesions are very rare, and this occurrence in anaplastic oligodendroglioma is exceptional. Only 16 cases of symptomatic spinal cord metastasis from brain oligodendroglioma have been reported in the literature. Case report: We present the case of a 42 years old woman with multiple symptomatic spinal cord metastasis discovered one year after surgical removal and postoperative radiotherapy for a right fronto-temporal anaplastic oligodendroglioma (grade III WHO). Conclusion: Although spinal cord metastasis from brain anaplastic oligodendroglioma is very rare, in our opinion it could be useful to perform screening spine MRIs to early detect the eventual diffusion of the oncologic disease. Differently, spinal MRI should be mandatory in all patients in whom an eventual reoperation could be proposed, because the detection of spinal localizations indicates a rapid poor prognosis and an eventual reoperation could be useless in terms of prolonged survival time.

Background Previous evidence showed abnormal posterior sources of resting-state electroencephalographic (rsEEG) delta ( 4 Hz) and alpha (about 8–12 Hz) rhythms in patients with Parkinson’s disease (PD) as cortical neural synchronization markers in quiet wakefulness. We hypothesized that a relatively short computerized cognitive training in PD patients might affect these mechanisms. Methods Clinical and rsEEG data were collected in PD patients with cognitive deficits (e.g., dementia or mild cognitive impairment), undergoing a standard levodopa therapy, and normal elderly (Nold) subjects. The rsEEG data in PD patients were recorded in three phases: before intervention (baseline), after two weeks of a computerized cognitive training (executive and episodic memory functions), and after two weeks of a computerized control procedure (watching favorite videos), in a cross-over design. Cortical rsEEG sources were estimated by exact low-resolution brain electromagnetic tomography (eLORETA). Results During baseline recordings, the PD group showed reduced posterior alpha and increased widespread delta source activities compared to the Nold group. In PD patients, the widespread delta source activities significantly decreased after cognitive training but not after the control intervention. Conclusions These results suggest that in PD patients with cognitive deficits a relatively short computerized cognitive training may have beneficial effects on cortical neural synchronization mechanisms generating abnormal cortical delta rhythms in quiet wakefulness.

Human cystic echinococcosis (CE) is a zoonosis caused by the larval stage of theEchinococcus granulosusand the most common sites affected are the liver and lung in approximately 80–90% of cases. The hydatid bone represents the 0.5–2.5% of all cases and localization cord is present about 50% of the time. This benign and commonly asymptomatic disease may simulate an aggressive malignancy because of osseous destruction and aggressive extension. We report a case of a 42-year-old male patient, presented with an unusual spinal hydatidosis relapse, related to anthelmintic drug therapy withdrawal after 10-year treatment. The man had previous excision of chest and hepatic hydatid cysts (resp., 10 and 3 years ago) and after primary mediastinal and spinal involvement (3 years ago) he was lost to follow-up and discontinued drug therapy. The patient underwent surgery and the postoperative histopathology confirmed the diagnosis. The patient recovered with no complications. Despite significant progress in diagnostic imaging, pharmacological and surgical therapy, spinal CE remains associated with high morbidity.

Radiosurgery (RS) and hypofractionated stereotactic radiotherapy (HSRT) were performed in 23 and 22 patients respectively for the treatment of trigeminal neuralgia. RS and HSRT were performed with a dedicated linear accelerator (LINAC): an invasive frame (for RS) or a relocatable stereotactic frame fitted with a thermoplastic mask and bite blocks (HSRT) were used for positioning patients. The RS treatment delivered 40 Gy in a single fraction, or for HSRT, the equivalent radiobiological fractionated dose – a total of 72 Gy in six fractions. The target (the retrogasserian cisternal portion of the trigeminal nerve) was identified by fusion of CT scans with 1-mm-thick T2-weighted MRI, and the radiant dose was delivered by a 10-mm-diameter cylindrical collimator. The results were evaluated using the Barrow Neurological Institute pain scale during follow-up (mean 3.9 years). The 95% isodose was applied to the entire target volume. After RS (23 patients), Class 1 results were observed in 10 patients; Class II in nine, Class IIIa in two, Class IIIb in one, and Class V results in one patient. Facial numbness occurred in two (8.7%) patients, and the trigeminal neuralgia recurred in two patients (8.7%). Following HSRT (22 patients), Class I results were achieved in eight patients, Class II in eight, Class IIIa in four, and Class IIIb in two patients; recurrence occurred in six (27.5%), and there were no complications. Thus, both RS and HSRT provided effective and safe therapy for the treatment of trigeminal neuralgia. Patients who underwent RS experienced better pain relief and a lower recurrence rate, whereas those who underwent HRST had no side effects, and in particular, no facial numbness.

Cranio-spinal junction tumors are usually approached through posterior, postero-lateral and far lateral approaches but, in case of prevalently anterior extension, with posterior and postero-lateral displacement of brainstem, anterior transoral approach should be considered to achieve a satisfactory tumor removal. Anterior transoral approach allows a direct exposition of the tumor without necessity of nervous/vascular structures manipulation. Postoperative instability is not frequent, and usually posterior stabilization is rarely required. Although transoral approach allows removing only the median part of the tumor’s and in few cases radical removal can be performed, it presents an extremely low rate of new neurological deficit and a rapid resumption of vital activities. Postoperative tumor remnant can be treated, in our experience, with hypofractionated stereotactic radiotherapy with very satisfactory results concerning tumor regrow and recurrence. We believe that in the modern era its capital to deal with this extremely challenging tumor’s with a different goal: to achieve the maximal clinical result, not the maximal surgical resection at all costs.

Evidence suggests an association between low serum 25-hydroxy-vitamin D3 [25(OH)D3] levels and the presence and prognosis of liver disease. Vitamin D receptor (VDR) has been widely detected in the liver, but its expression in the course of liver disease has never been investigated. We evaluated the hepatic expression of VDR along with that of vitamin D 25-hydroxylases in patients with nonalcoholic steatohepatitis (NASH) or chronic hepatitis C (CHC) and its relationship with hepatic histological features and serum 25(OH)D3 levels. We evaluated 61 patients (25 NASH and 36 CHC) who had undergone liver biopsy for clinical purposes and 20 subjects without liver disease. Serum 25(OH)D3 was measured via colorimetric assay. Expression of VDR, CYP2R1, and CYP27A1 was evaluated via immunohistochemistry in hepatocytes, cholangiocytes, and liver inflammatory cells. Parenchymal and inflammatory cells from liver biopsies of patients with NASH and CHC expressed VDR, CYP2R1, and CYP27A1. In NASH patients, VDR expression on cholangiocytes was inversely correlated with steatosis severity (P < 0.02), lobular inflammation (P < 0.01), and nonalcoholic fatty liver disease score (P < 0.03). Moreover, expression of CYP2R1 in hepatocytes correlated strongly with VDR positivity on liver inflammatory cells. In CHC subjects, fibrosis stage was associated with low hepatic CYP27A1 expression, whereas portal inflammation was significantly higher in patients with VDR-negative inflammatory cells (P < 0.009) and low VDR expression in hepatocytes (P < 0.03). Conclusion: VDR is widely expressed in the liver and inflammatory cells of chronic liver disease patients and its expression is negatively associated with the severity of liver histology in both NASH and CHC patients. These data suggest that vitamin D/VDR system may play a role in the progression of metabolic and viral chronic liver damage. (HEPATOLOGY 2012;56:2180–2187)

Up to one-third of patients with cystic fibrosis (CF) awaiting lung transplantation (LTX) die while waiting. Inclusion of computed tomography (CT) scores may improve survival prediction models such as the lung allocation score (LAS).This study investigated the association between CT and survival in patients with CF screened for LTX.Clinical data and chest CTs of 411 patients with CF screened for LTX between 1990 and 2005 were collected from 17 centers. CTs were scored with the Severe Advanced Lung Disease (SALD) four-category scoring system, including the components infection/inflammation (INF), air trapping/hypoperfusion (AT), normal/hyperperfusion (NOR), and bulla/cysts (BUL). The volume of each component was computed using semiautomated software. Survival analysis included Kaplan-Meier curves and Cox regression models.Three hundred and sixty-six (186 males) of 411 patients entered the waiting list (median age, 23 yr; range, 5-58 yr). Subsequently, 67 of 366 (18%) died while waiting, 263 of 366 (72%) underwent LTX, and 36 of 366 (10%) were awaiting LTX at the census date. INF and LAS were significantly associated with waiting list mortality in univariate analyses. The multivariate Cox model including INF and LAS grouped in tertiles, and comparing tertiles 2 and 3 with tertile 1, showed waiting list mortality hazard ratios of 1.62 (95% confidence interval [95% CI], 0.78-3.36; P = 0.19) and 2.65 (95% CI, 1.35-5.20; P = 0.005) for INF, and 1.42 (95% CI, 0.63-3.24; P = 0.40), and 2.32 (95% CI, 1.17-4.60; P = 0.016) for LAS, respectively. These results indicated that INF and LAS had significant, independent predictive value for survival.CT score INF correlates with survival, and adds to the predictive value of LAS.

Several radiographic diagnostic techniques are currently available to assess the potential involvement of mediastinal lymph nodes in thoracic oncology. In particular, computed tomography and magnetic resonance imaging have been repeatedly validated; these techniques allow adequate imaging with a reasonable accuracy. The morphologic information provided by these techniques is crucial to stage lung cancer and plan treatment. These techniques are also extremely useful to evaluate other disorders and differentiate malignancy from benign disease.

Bronchoscopic lung volume reduction (BLVR) is a novel emphysema therapy. We evaluated long-term outcome in patients with heterogeneous emphysema undergoing BLVR with one-way valves. 40 patients undergoing unilateral BLVR entered our study. Pre-operative mean forced expiratory volume in 1 s (FEV(1)) was 0.88 L · s(-1) (23%), total lung capacity was 7.45 L (121%), intrathoracic gas volume was 6 L (174%), residual volume (RV) was 5.2 L (232%), and the 6-min walk test (6MWT) was 286 m. All patients required supplemental oxygen; the Medical Research Council (MRC) dyspnoea score was 3.9. High-resolution computed tomography (HRCT) results were reviewed to assess the presence of interlobar fissures. 33 patients had a follow-up of12 months (median 32 months). 37.5% of the patients had visible interlobar fissures. 40% of the patients died during follow-up. Three patients were transplanted and one underwent lung volume reduction surgery. Supplemental oxygen, FEV(1), RV, 6MWT and MRC score showed a statistically significant improvement (p ≤ 0.0001, p = 0.004, p = 0.03, p = 0.003 and p0.0001, respectively). Patients with visible fissures had a functional advantage. BLVR is feasible and safe. Long-term sustained improvements can be achieved. HRCT-visible interlobar fissures are a favourable prognostic factor.

Combined PET/MR is a relatively new technique and so far there has been a very limited report of the potential simultaneous PET/MR and PET/CT application in the evaluation of neuroendocrine tumours. The present study aimed to compare "Ga-DOTATATE PET/CT and PET/MR imaging in patients with known neuroendocrine tumours (NET) and assess the confidence in anatomic lesion detection and localization. We analysed the data of 37 NET patients who underwent both 68Ga-DOTATATE PET/CT and PET/MR using the same injected activity. Visual findings by two observers of the two modalities were recorded. SUV max of both primary tumour and liver lesions for both modalities and PET/MR derived apparent diffusion coefficient (ADC) values were measured. To study the value of additional MRI sequences, the differences in performance between PET with T1+T2w, PET with DWI reads, and PET with post contrast was assessed. No significant differences between the two modalities were seen regarding the number of patients affected by primary or metastatic disease. However, counting the number of lesions per patient, both observers were able to recognize more liver lesions in MRI T1 and T2. The interclass correlation coefficient (ICC) demonstrated a strong correlation between SUV max derived from PET/CT and PET/MR in both primary lesions (ICC = 0.92; p = 0.001) and liver (ICC = 0.882; p = 0.001). In the evaluation of lesion per patient, PET+ contrast and DWI detected more metastasis than the evaluation of PET +T1 and T2 alone. There was no significant correlation between ADC values and PET/MR SUV max of the tumour (respectively: p = 0.43, p 0.88 and p = 0.295). PET/MRI has comparable accuracy in localization and staging to PET/CT, and has a potential to become a valid alternative to PET/CT in staging and follow up of NET patients, with advantages in the characterization of liver lesions. In our study DWI and contrast helped to detect more lesions.

Mud-bath therapy plays a primary role in the treatment and prevention of osteoarthritis that has been recognised since antiquity. Numerous studies have demonstrated its clinical benefits and its effects on inflammatory mediators (interleukins), the immune system, cenesthesic factors (endorphins), and the diencephalic–pituitary–adrenal axis. This study was conducted to assess the efficacy of mud-bath therapy with mineral water from the Sillene Spring at Italy’s Chianciano Spa in patients with osteoarthritis of the knee. Patients (n = 61) were divided into two groups. Group A underwent three cycles of mud-based spa therapy over a year’s time, whereas group B did not. Clinical conditions, visual analogue scale pain ratings, and Lequesne indexes of the two groups were compared. We also compared these same parameters in the patients of the two groups that were following the therapy with drugs and in the patients of the group A before and after spa treatment. The percentage of patients with no symptoms or mild symptoms was higher in group A than in group B. Within group A, this percentage was higher after treatment than before spa therapy. Even in the comparison between the patients of the two groups that were following the therapy with drug, the results was that in group A the percentage of patients with no symptoms or mild symptoms was higher than in group B. Statistical analyses based on various tests revealed that almost all these differences were highly significant. No adverse effects were observed in any of the patients in group A. In conclusion, the mud-bath therapy performed at Chianciano Spa with Sillene Spring water remarkably improved the clinical conditions of patients with knee arthritis and significantly reduces the frequency and severity of symptoms and the disability they cause.