Performance of Fully-Automated High-Throughput Plasma Biomarker Assays for Alzheimer's Disease in Amnestic Mild Cognitive Impairment Subjects.

INTRODUCTION: Novel plasma biomarkers are promising for identifying Alzheimer's disease (AD) pathological processes in vivo, but most currently employed assays have limitations precluding widespread use. METHODS: CSF and plasma samples were collected from seventy amnestic mild cognitive impairment (aMCI) subjects, stratified as A+ and A-. CSF Aß40, Aß42, p-tau181 and t-tau and plasma Aß40, Aß42 and p-tau181 quantification were conducted using the Lumipulse G assays (Fujirebio), to evaluate the diagnostic performance of plasma biomarkers and assess their associations with CSF biomarkers. RESULTS: All plasma biomarkers except Aß40 showed a very good accuracy in distinguishing A+ aMCI from A- aMCI, Aß42/p-tau181 ratio being the most accurate (AUC 0.895, sensitivity 95.1%, specificity 82.8%). Plasma biomarkers levels were significantly associated with CSF biomarkers concentration. DISCUSSION: High-throughput and fully-automated plasma assays could be helpful in discriminating with high accuracy between aMCI in the AD continuum and aMCI unlikely due to AD in clinical settings.

Cortical connectivity and memory performance in cognitive decline: A study via graph theory from EEG data.

Functional brain abnormalities including memory loss are found to be associated with pathological changes in connectivity and network neural structures. Alzheimer's disease (AD) interferes with memory formation from the molecular level, to synaptic functions and neural networks organization. Here, we determined whether brain connectivity of resting-state networks correlate with memory in patients affected by AD and in subjects with mild cognitive impairment (MCI). One hundred and forty-four subjects were recruited: 70 AD (MMSE Mini Mental State Evaluation 21.4), 50 MCI (MMSE 25.2) and 24 healthy subjects (MMSE 29.8). Undirected and weighted cortical brain network was built to evaluate graph core measures to obtain Small World parameters. eLORETA lagged linear connectivity as extracted by electroencephalogram (EEG) signals was used to weight the network. A high statistical correlation between Small World and memory performance was found. Namely, higher Small World characteristic in EEG gamma frequency band during the resting state, better performance in short-term memory as evaluated by the digit span tests. Such Small World pattern might represent a biomarker of working memory impairment in older people both in physiological and pathological conditions.

Depression in multiple sclerosis: effect of brain derived neurotrophic factor Val66Met polymorphism and disease perception.

BACKGROUND AND PURPOSE: Depression is common amongst subjects with multiple sclerosis (MS), and several investigations have explored different determinants of this condition, including physical disability, psychological and psychosocial factors. The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with depression. The aim of this study was to analyze the influence of disease-related factors, BDNF Val66Met polymorphism and perception of disease on the severity of depression in MS. METHOD: In total, 136 MS patients (88 women) were recruited and genotyped for BDNF rs6265 polymorphism at nucleotide 196 (G/A) using 'high resolution melting'. Depressive symptoms were assessed by the Multiple Sclerosis Depression Rating Scale. Perception of health status was assessed using the SF-36 questionnaire. RESULTS: A multivariable linear regression model showed that the best predictors of depression were the SF-36 General health (ß = -0.209; P = 0.013), Mental health (ß = -0.410; P < 0.001) and Social activity (ß = -0.195; P = 0.035) scores; physical disability (assessed by the Extended Disability Status Scale score) was directly correlated to depression severity on univariate analysis, but it was not a relevant predictor of depression on multivariate analysis; other variables directly related to the disease (treatment, annual relapsing rate) and the BDNF Val66Met polymorphism were not significantly associated with depression. CONCLUSION: Perception of the health status is the principal predictor of depressive symptoms in our sample. This result supports the hypothesis that the subjective interpretation of the disease's consequences is one of the main factors in determining depression in MS.

[Vaginal metastasis revealing an adenocarcinoma of the transverse colon]. / Métastase vaginale révélatrice d'un adénocarcinome du côlon transverse.

Secondary localization to vagina had a severe prognosis, suggesting a disseminated metatastic disease. We report the case of prevalent vaginal metastasis of adenocarcinoma of the transverse colon. A 65 years old patient has consulted for vaginal mass. After delayed diagnosis, she presented with disseminated metastatic disease with peritoneal carcinomatosis. After neoadjuvant chemotherapy, the following treatment consisted of complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and vaginal adjuvant radiotherapy. No recurrence occurred after one year. Vaginal metastasis of colon cancer are rare. The dark prognosis might justify a systematic gynecological examination of women presenting colorectal neoplasy.

Intraoperative radiological margin assessment in breast-conserving surgery.

UNLABELLED: A prospective study was lead in order to analyze the accuracy of an X-ray device settled in the operating room for margin assessment, when performing breast-conserving surgery. PATIENTS AND METHODS: One hundred and seventy patients were included. All lesions were visible on the preoperative mammograms. An intraoperative X-ray of the lumpectomy specimen was systematically performed for margins assessment. Final histological data were collected and the accuracy of intraoperative specimen radiography (IOSR) for margin assessment was analyzed. RESULTS: IOSR allowed an evaluation of margins status in 155 cases (91.2%). After final histological examination, the positive margins rate would have been 6.5% if margin assessment had relied only on IOSR. CONCLUSION: Margin assessment with a two-dimensional X-ray device would have allowed the achievement of negative margins in 93.5% of the cases. Moreover, this procedure allows important time-saving and could have a substantial economical impact.

[Conservative treatment of a compressive adenomyosis: report of a case]. / Traitement conservateur d'une adénomyose compressive: à propos d'un cas.

Adenomyosis is frequent, mostly asymptomatic. A hypertrophy of the smooth muscular cells around ectopic endometrial glands might induce a compressive syndrome. We report the case of an embolization of a voluminous adenomyosic uterus which has triggered venous iliac's compression in patient refusing surgery. This treatment was efficient in reduction of uterin volume, without recurrence after three years. MR imaging is the exam of choice particularly when diagnosis is still uncertain and allows a non-invasive and good evaluation, and follow-up. Embolization is not actually recommended. But, it appears to be efficient, relatively safe and contributes to the conservation of fertility.

The Multiple Features Target Cancellation (MFTC): an attentional visual conjunction search test. Normative values for the Italian population.

Several studies, showing that attention disorders during encoding reduce later memory performance, have stressed the critical role of attention for the formation of durable memory traces. Accordingly, some studies suggest that attentive disturbances, together with declarative memory defects, can constitute the earliest cognitive disorders in Alzheimer's disease. Therefore, the analysis of these disorders can contribute to identify different forms of dementia and to detect demented patients characterized by a faster cognitive decline. In this study, we report the normative data (gathered in a large Italian population) of a short test that assess the ability to detect stimuli characterized by a conjunction of features: the 'Multiple Features Targets Cancellation' task (MFTC). Our sample of 465 subjects was composed by urban and rural people. Multiple linear regression analyses revealed significant relation of false alarms with age and educational level, and of time of execution with age, educational level and gender. Regression analyses on accuracy scores did not show any significant correlation with demographics variables. Based on non-parametric techniques, cutoff scores were obtained on the corrected scores of the patients, and equivalent scores were derived for each measure. The MFTC task represents a useful tool that explores attentional disorders (and in particular conjunction search disturbances) and that could be helpful both in discriminating different forms of dementia and to detect mild cognitive impairment patients at risk of conversion to dementia.

Correlations between peripheral blood mononuclear cell production of BDNF, TNF-alpha, IL-6, IL-10 and cognitive performances in multiple sclerosis patients.

The aim of this study was to investigate the role of Brain Derived Neurotrophic Factor (BDNF) and inflammatory factors in the development of cognitive dysfunctions in Multiple Sclerosis (MS). We correlated peripheral blood mononuclear cell (PBMC) production of BDNF, Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin (IL)-6 and IL-10 with performances on specific neuropsychological tasks in a selected series of MS patients. We studied a sample of 30 patients with relapsing-remitting (RR)MS, segregated by gender and matched for age, education, disease duration, type of immunomodulating therapy, degree of disability and overall cognitive status. We found that low BDNF levels were correlated with increased time of execution on a divided attention and visual scanning task whereas high levels of IL-6 were correlated with low Mini Mental State Examination scores. We did not observe any significant correlations between IL-10, TNF-alpha levels and cognitive performances in our patients. In conclusion our study shows a correlation between low BDNF and high IL-6 production by PBMCs and poorer performances in cognitive tasks in RRMS patients suggesting a possible role of these factors in cognitive impairment in MS.

In vivo functional evaluation of central cholinergic circuits in vascular dementia.

OBJECTIVE: Central cholinergic circuits of human brain can be tested non-invasively by coupling peripheral nerve stimulation with transcranial magnetic stimulation of motor cortex. This test, named short latency afferent inhibition (SAI) has been shown in healthy subjects to be sensitive to the blockage of muscarinic acetylcholine receptors and it is impaired in Alzheimer disease (AD) patients, a cholinergic form of dementia, while it is normal in non-cholinergic forms of dementia such as fronto-temporal dementia. The objective of present study was to evaluate central cholinergic circuits in patients with Vascular Dementia (VaD). METHODS: We evaluated SAI in a group of patients with VaD and compared the data with those from a group of AD patients and a control group of age-matched healthy individuals. RESULTS: Mean SAI was normal in VaD patients while it was significantly reduced in AD patients. The analysis of individual data showed abnormal SAI in 75% of AD and in only 25% of VaD. CONCLUSIONS: SAI is normal in most of VaD patients in contrast with AD patients. This test might be used for the functional evaluation of central cholinergic circuits in VaD patients. SIGNIFICANCE: SAI testing may represent a useful additional tool for the evaluation of patients with VaD however, further studies are required in order to evaluate whether this method can be used for the differential diagnosis between pure VaD and different forms of dementia.

Cognitive impairment in myotonic dystrophy type 1 (DM1): a longitudinal follow-up study.

OBJECTIVE: To characterize the progression of the cognitive involvement in patients affected by myotonic dystrophy type 1 (DM1) by a longitudinal neuropsychological follow-up study. METHODS: In a previous study we documented an ageing-related decline of frontal and temporal cognitive functions in juvenile/adult forms of DM1, irrespectively of the n(CTG) in leukocytes and the severity of muscle weakness. Here we present the results of a neuropsychological follow-up study performed in 34 out of 70 DM1 patients previously studied. Patients were divided into four groups according to their genotype (E1:50-150; E2:150-500; E3:500-1000; E4: >1000 CTG). The neuropsychological test battery included MMSE, memory, linguistic, level, praxis, attentional and frontal-executive tasks. Statistical analysis was performed by One way MANOVA with repeated measures analysis and by Wilcoxon match paired test. RESULTS: The whole group of patients showed a significant deterioration in linguistic functions, together with a tendency towards decline in executive abilities, confirming a predominant involvement of cognitive functions subserved by fronto-temporal areas. We found no significant correlation between the progression of cognitive decline and the n(CTG) in leukocytes. Moreover, we observed that patients belonging to E2 group, with the highest mean age, got scores lower than E3 patients, with particular regard both to linguistic and executive tasks. CONCLUSIONS: These data support our previous hypothesis that the cognitive damage is confined to frontotemporal functions in adult DM1 patients, with a tendency towards a decline with aging.

Fibrinogen apheresis in the treatment of peripheral arterial disease.

BACKGROUND: Fibrinogen is mainly responsible for determining the viscosity of whole blood. In peripheral arterial disease (PAD) the fibrinogen concentration seems to affect the microcirculation flow. AIM: To study the effects of an abrupt reduction of fibrinogen on the hemodynamics of the lower extremities and the clinical picture of patients with PAD. METHODS: Ten patients affected by various stages of PAD underwent 1 session of fibrinogen apheresis (TheraSorb, Miltenyi Biotec, Germany). Laboratory parameters of endothelial activation were assessed before and after the session, as well as walking distance (WD), the ankle-brachial index and laser Doppler flowmetry. RESULTS: A significant reduction in the laboratory parameters was observed: fibrinogen (50%), total cholesterol (18%), LDL cholesterol (24%), sE-selectin (23%), sICAM-1 (19%) and sVCAM-1 (10%). The procoagulant factors, factor VIII and von Willebrand factor, did not vary significantly. Both pain-free and total WD were significantly improved (p < 0.003 and p <0.006, respectively), the ankle-brachial index remained unchanged, and laser Doppler flowmetry showed a modest but not significant increase. CONCLUSIONS: Fibrinogen apheresis allowed us to study the effects of an acute modification of fibrinogen in PAD, on both some aspects of the endothelial function and on the hemodynamics, demonstrating an improvement of WD and a minimal increase in the skin microcirculation.

Clusters of cognitive and behavioral disorders clearly distinguish primary progressive aphasia from frontal lobe dementia, and Alzheimer's disease.

BACKGROUND/AIMS: Frontal lobe dementia (FLD) and primary nonfluent progressive aphasia (PnPA) are two forms of frontotemporal lobe degeneration. The relationship between these conditions remains unclear. Our study aimed to better define the behavioral and cognitive clusters characterizing PnPA patients. METHODS: We cognitively and behaviorally evaluated three groups of newly diagnosed patients affected by Alzheimer's disease (AD, n=20), FLD (n=22) and PnPA (n=10), in order to assess the cognitive-behavioral pattern of PnPA, compared to both FLD and AD. RESULTS: We found, as expected, worse performances in episodic memory in AD, of both the verbal fluency and naming tasks in PnPA, while FLD mainly showed behavioral disorders associated with an unremarkable deficit in the executive tasks. PnPA was not characterized by any significant behavioral disorders. Factor analysis-extracted three main factors ('mnesic', 'behavioral' and 'linguistic') clearly correlated to each group. A discriminant analysis based on the extracted factors correctly classified 84.6% of all patients. CONCLUSION: The evidence of a characteristics cognitive profile, without any significant behavioral changes, highlights that PnPA is different from other forms of frontotemporal lobe degeneration regarding both the cognitive and behavioral patterns; thus, it should be considered independently in further studies.

[Assaults and nuisances in health care environment]. / Aggressioni e molestie nelle attività sanitarie.

A descriptive exploratory survey was used to investigate the occurrence of physical workplace violence among health care workers as well as the complaints and responses to such violence. The questionnaire was used for collecting data from a sample of 355 workers. Results showed that 25.6% of hospital workers reported physical aggression at any time of the working life, 8.5% in the last year. Injured workers showed significantly higher environmental complaint score than other workers. The results of the study indicated the importance of adopting hospital policies for dealing with incidents of violence.

Study on the effectiveness of a nifedipine gel for treatment of Raynaud?s phenomenon.

The aim of this study is to evaluate the efficacy of a nifedipine gel in patients with primary or secondary Raynaud?s phenomenon. Photopletismography was the instrumental examination test used to evaluate recovery time (time necessary for recuperation of normal capillary circulation) in 17 patients with primary or secondary Raynaud?s phenomenon before and after the application of the gel. It emerged that of the 17 patients who used the gel, in 3 cases the recovery time was reduced, in 9 cases the recovery time was cancelled (no spasm occurred), in 5 cases the recovery time was not modified. Therefore, in more than 70 percent of patients the drug had a positive effect. Besides, 50 percent of the patients referred an improvement of the subjective symptomatology with reduction of cooling, torpidity, ache and paresthesias of the fingers. The results obtained, even if related to a restricted number of patients and to a brief interval of time, show the effectiveness of this drug in patients with primary or secondary Raynaud?s phenomenon. We believe that these results, presented here for the first time, are important for investigators involved in the study of Raynaud?s disease.

Capillaroscopy of the dorsal skin of the hands in hereditary hemorrhagic telangiectasia.

BACKGROUND: Cutaneous telangiectases are manifestations of hereditary hemorrhagic telangiectasia (HHT), a dominantly inherited disorder. Telangiectases have been studied by skin biopsy, and recently by nailfold capillaroscopy. AIM: To confirm the diagnostic role of nailfold capillaroscopy, and assess the value of skin capillaroscopy of the dorsum of the hands in HHT. DESIGN: Prospective clinical investigation. METHODS: Using a Wild Heerbrugg-M650 microscope, we studied the nailfolds and dorsum of the hands of 88 patients (37 females, 51 males, mean age 39.7 +/- 18.4 years), including 85 with positive genetic testing and three with clinical diagnosis (at least three clinical criteria but a negative genetic test) and 27 controls (13 females, 14 males, mean age 38.6 +/- 19.6 years). RESULTS: Microscopic telangiectases were observed on the dorsum of the hands in 80/88 patients (91%): 77 with positive and three with negative genetic tests. No control showed vascular abnormalities. In six patients (7%), nailfold capillaroscopy showed pseudo-megacapillaries and megacapillaries; the remaining 82 (93%) and all controls, had normal capillaroscopic patterns. DISCUSSION: HHT can induce morphological changes in microcirculation that are more easily detectable on the dorsum of the hands than in the nailfold. Microscopic lesions without macroscopic telangiectases were also noted, suggesting the need for further research. Capillaroscopy may provide an additional non-invasive diagnostic criterion for HHT.

[Epidemiologic observations on the subject of phlebopathy of the legs and its dermatologic complications]. / Osservazioni epidemiologiche in tema di flebopatie degli arti inferiori e loro complicanze dermatologiche.

The authors carried out an epidemiological study on a group of 10032 patients with chronic venous insufficiency, composed of 2686 males (26.77%) and 7346 females (73.23%). The case report is divided into varicose diseases (83.30%) and sequelae of deep vein thrombosis (16.70%). As well as the relationship between sex and age is considered rate of dermatological complications, with regard both to the type of venous diseases (65.54% varicose and 34.46% post-thrombotic) and to their clinical manifestations. As well as any family connection, various environmental factors are taken into account such as the patient's work, noxae iatrogenic, pregnancy and obesity.