A new study protocol for in-vivo assessment of tumor diagnosis and microscopic tumor infiltration at the resection cavity in central nervous system tumors by a new miniature confocal endomicroscope (CONVIVO system).

BACKGROUND: Confocal laser technology has been recently suggested as a promising method to obtain near real-time intraoperative histological data. We recently demonstrated the accuracy of a newly designed confocal endomiscroscope (CONVIVO) in offering an intraoperative diagnosis during high-grade gliomas (HGGs) removal in an ex vivo study. With this work we aim to perform a standardized, prospective and blinded-to-histological section study for evaluating the potentiality of CONVIVO in offering in-vivo data regarding histological diagnosis and presence of tumor at margins during resection of central nervous system (CNS) tumors. METHODS: This prospective, observational, standardized, blinded-to-histological section, clinical trial was approved by the institutional review board in Carlo Besta Neurologic Institute IRCCS Foundation in Milan and is expected to last 24 months. 75 patients will be included, with at least 53 of them being HGGs based on the statistical sample size calculation. Main objectives will be the assessing of the concordance of tumor diagnoses between CONVIVO images and frozen section at the center of all tumor subtypes and the evaluation of the accuracy of CONVIVO in the identification of tumor tissue at the margins, compared to standard histology. For this purpose, "virtual biopsies" and physical biopsies will be performed directly on patient tumor tissue and surrounding brain parenchima during tumor resection, comparing the results of CONVIVO analysis and frozen and histological sections. RESULTS: Despite promising preliminary data on ex vivo usefulness of CLE machines are emerging in literature, still few studies are available when looking at in vivo potentiality of CONVIVO. At this regard, this study will be the first work where a standardized, prospective, and blinded-to-histological section CONVIVO analysis will be performed in an in-vivo setting in neuro-oncological surgery. CONCLUSIONS: We hypothesize that this new technique may have a role in offering data regarding presence of tumor tissue, eventually giving an intraoperative diagnosis in neuro-oncological surgery, rendering more fluid the decision-making process in the operating room. Furthermore, the result of this study will provide a solid base for further expanding the clinical applications of confocal machines in neurosurgery.

Reliable virtual clinical assessment in spino-bulbar muscular atrophy (SBMA).

BACKGROUND: Spino-bulbar muscular atrophy (SBMA), caused by a CAG repeat expansion in the androgen receptor gene, affects adult men and results in muscle atrophy and weakness in the bulbar and limb muscles and signs of partial androgen insensitivity. During the COVID-19 pandemic, outpatients' visits have been reduced to preserve safety of frail patients, and telehealth was largely employed. METHODS: From April to November 2020, we monitored 12 patients with SBMA with telehealth and administered remotely two clinical scales currently used for SBMA: Adult Myopathy Assessment Tool (AMAT) and SBMA-Functional Rating Scale (SBMA-FRS). We compared results with previous and subsequent in-person visits' scores, and assessed the longitudinal changes in AMAT and SBMA-FRS scores during 7 years through the repeated measures analysis of variance (ANOVA). RESULTS: Repeated measures ANOVA of AMAT scores collected during 7 years and including tele-AMAT evaluation showed a steady mean decline of 1-2 points per year. A similar trend of SBMA-FRS scores, with a mean decline per year of about 1 point, was observed. There was no relevant deviation from the model prediction. CONCLUSIONS: Our data show that telehealth is a valid tool to monitor patients with SBMA: AMAT and SBMA-FRS scales can be effectively, reliably and easily administered remotely.

Quality of life assessment in adult spinal muscular atrophy patients treated with nusinersen.

OBJECTIVE: To retrospectively evaluate quality of life (QoL) in a large multicenter cohort of adult patients affected by spinal muscular atrophy (SMA) during nusinersen treatment. METHODS: We included adult (≥ 18 years) patients clinically and genetically defined as SMA2, SMA3 and SMA4, who started nusinersen treatment in adulthood. QoL was rated by the Individualized Neuromuscular Quality of Life (INQoL) questionnaire. Concurrent motor function evaluation included the Hammersmith Functional Motor Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM), the 6 min walking test (6MWT). RESULTS: 189 completed questionnaires were collected during a 14 months' treatment period. 78 patients were included (7 SMA2 and 69 SMA3 and 2 SMA4) with mean disease duration at first nusinersen administration of 33.2 years (± 12.5 years). All the scores for each INQoL domain (weakness, fatigue, activities, independence, social relationship, emotions, body images) and the derived QoL total score, significantly improved during the observation period, except the muscle locking and pain items. Exploratory analyses suggested that emotions and social relationships were more relevant issues for females compared to males. Social relationships were affected also by a longer disease duration (> 30 years). In SMA3 non-walker patients, activities ameliorate better compared to walkers. The HFMSE and RULM significantly improved from baseline; however, no associations with QoL total score and weakness, activities or independence were demonstrated. CONCLUSION: In our cohort, adult SMA patients showed a global improvement at the INQoL assessment over 14 months of nusinersen treatment. QoL assessment is relevant to SMA multidisciplinary evaluation.

Discrimination of MSA-P and MSA-C by RT-QuIC analysis of olfactory mucosa: the first assessment of assay reproducibility between two specialized laboratories.

BACKGROUND: Detection of the pathological and disease-associated alpha-synuclein (αSynD) in the brain is required to formulate the definitive diagnosis of multiple system atrophy (MSA) and Parkinson's disease (PD). We recently showed that αSynD can be detected in the olfactory mucosa (OM) of MSA and PD patients. For this reason, we have performed the first interlaboratory study based on α-synuclein Real-Time Quaking-Induced Conversion (αSyn_RT-QuIC) analysis of OM samples collected from PD and MSA patients with the parkinsonian (MSA-P) and cerebellar (MSA-C) phenotypes. METHODS: OM samples were prospectively collected from patients with a probable diagnosis of MSA-P (n = 20, mean disease duration 4.4 years), MSA-C (n = 10, mean disease duration 4 years), PD (n = 13, mean disease duration 8 years), and healthy control subjects (HS) (n = 11). Each sample was analyzed by αSyn_RT-QuIC in two independent specialized laboratories, one located in Italy (ITA-lab) and one located in the USA (USA-lab). Both laboratories have developed and used harmonized αSyn_RT-QuIC analytical procedures. Results were correlated with demographic and clinical data. RESULTS: The αSyn_RT-QuIC analysis reached a 96% interrater agreement of results (IAR) between laboratories (Kappa = 0.93, 95% CI 0.83-1.00). In particular, αSyn_RT-QuIC seeding activity was found in the OM of 9/13 patients with PD (sensitivity 69%, IAR 100%) and 18/20 patients with MSA-P (sensitivity 90%, IAR 100%). Interestingly, samples collected from patients with MSA-C did not induce αSyn_RT-QuIC seeding activity, except for one subject in USA-lab. Therefore, we found that MSA-P and MSA-C induced opposite effects. Regardless of disease diagnosis, the αSyn_RT-QuIC seeding activity correlated with some clinical parameters, including the rigidity and postural instability. CONCLUSIONS: Our study provides evidence that OM-αSynD may serve as a novel biomarker for accurate clinical diagnoses of PD, MSA-P, and MSA-C. Moreover, αSyn_RT-QuIC represents a reliable assay that can distinguish patients with MSA-P from those with MSA-C, and may lead to significant advancements in patients stratification and selection for emerging pharmacological treatments and clinical trials.

Diagnostic test accuracy of an automated device as a screening tool for fall risk assessment in community-residing elderly: A STARD compliant study.

We aimed to determine the accuracy and failure of OAK device, an automated screening, for the assessment of fall risk in a prospective cohort of healthy adults aged over 65 years. The algorithm for fall risk assessment of the centers for disease control and prevention (CDC) was used as reference standard. Of the 183 individuals recruited, the CDC algorithm classified 80 as being at moderate/high risk and 103 at low risk of falling. OAK device failure incidence was 4.9% (confidence interval [CI] upper limit 7.7%), below the preset threshold for futility-early termination of the study (i.e., not above 15%). The OAK device showed a sensitivity of 84% and a specificity of 67% (receiver operating characteristic [ROC] area 82%; 95% confidence interval [CI] 76-88%), not reaching the preplanned target sensitivity (not lower than 85%). Diagnostic accuracy was not far from the sensitivity levels similar to those obtained with other fall risk assessment. However, some limitations can be considered.ClinicalTrials.gov identifier: NCT02655796.

Conventional versus Ultrasound-Guided Transbronchial Needle Aspiration for the Diagnosis of Hilar/Mediastinal Lymph Adenopathies: A Randomized Controlled Trial.

BACKGROUND: Conventional transbronchial needle aspiration (c-TBNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are both valuable diagnostic techniques for the diagnosis of hilar/mediastinal lesions. Although a superiority of EBUS-TBNA over c-TBNA may be expected, evidence-based data on a direct comparison between these 2 procedures are still lacking. OBJECTIVES: We aimed to test the superiority of EBUS-TBNA over c-TBNA in a randomized trial and to evaluate the cost-effectiveness profile of a staged strategy, including c-TBNA as initial test followed by EBUS-TBNA, in case of inconclusive results at rapid on-site evaluation. METHODS: Eligible patients were randomized 1:1 to either the EBUS-TBNA or c-TBNA group. The primary endpoint was to test the superiority of EBUS-TBNA sensitivity over c-TBNA. The secondary endpoints included the sensitivity of the staged strategy, as well as costs and safety related to each procedure and to their sequential combination. RESULTS: A total of 253 patients were randomized to either EBUS-TBNA (n = 127) or c-TBNA (n = 126), and 31 patients of the c-TBNA group subsequently underwent EBUS-TBNA. The sensitivity of EBUS-TBNA was higher, but not significantly superior to that of c-TBNA (respectively. 92% [95% CI 87-97] and 82% [95% CI 75-90], p > 0.05). The sensitivity of the staged strategy was 94% (95% CI 89-98). No major adverse events occurred. CONCLUSIONS: EBUS-TBNA was the single best diagnostic tool, although not significantly superior to c-TBNA. Due to the favorable cost-effectiveness profile of their sequential combination, in selected scenarios with a high probability of success from the standard procedure, these should not be necessarily intended as competitive and the staged strategy could be considered in clinical practice.

Development and assessment of a website presenting evidence-based information for people with multiple sclerosis: the IN-DEEP project.

BACKGROUND: People with multiple sclerosis (MS) are increasingly using the Internet in the daily management of their condition. They search for high-quality information in plain language, from independent sources, based on reliable and up-to-date evidence. The Integrating and Deriving Evidence, Experiences and Preferences (IN-DEEP) project in Italy and Australia aimed to provide people with MS and family members with an online source of evidence-based information, starting from their information needs. This paper reports on the Italian project's website. METHODS: Contents, layout and wording were developed with people with MS and pilot-tested. The website was evaluated using an online 29-item questionnaire for ease of language, contents, navigation, and usefulness of information aimed at people with MS, family members and the general population. RESULTS: The website ( http://indeep.istituto-besta.it/) is structured in multiple levels of information. The first topic was interferons-ß for people with relapsing-remitting MS. In all, 433 people responded to the survey (276 people with MS, 68 family members and 89 others). The mean age was 45 years, almost 90% had a high school diploma, about 80% had relapsing-remitting MS, and the median disease duration was seven years. About 90% judged the website clear, understandable, useful, and easy to navigate. Ninety percent of people with MS and family members would recommend it to others. Sixty-two percent reported they felt confident in making decisions on interferons-ß after reading the website. CONCLUSIONS: The model was judged clear and useful. It could be adapted to other topics and diseases. Clinicians may find it useful in their relationship with patients.

Tobacco sales to minors in Italy.

AIMS AND BACKGROUND: One of the strategies to control tobacco is to limit purchase of cigarettes to minors. To understand the attitudes of Italian adults towards regulations to prevent minors from purchasing tobacco products, we added specific questions to the annual survey on smoking in Italy. METHODS: During March-April 2007, we conducted a survey on smoking on 3,057 subjects representative of the Italian population aged > or = 15 years. Two specific questions were included, one investigating the attitudes towards the proposed legislation prohibiting purchase of tobacco to individuals under 18 years of age (instead of 16 years) as a policy to reduce smoking prevalence and consumption. The second question asked whether the current tobacco sales-to-minors law was observed. RESULTS: Overall, 78% of Italians believed that a restriction of the current tobacco sales-to-minors law could be moderately to extremely effective as a strategy to decrease smoking prevalence and consumption. More than 90% of Italians reported that they had never seen in their lifetime a retailer refusing to sell cigarettes to an adolescent or requesting the minor's identification or age. CONCLUSIONS: A restriction of the legislation, increasing to 18 years the minimum age for purchasing tobacco, would limit access to tobacco products by minors, only if adopted together with systematic and effective enforcement measures.

Socio-demographic variation in smoking habits: Italy, 2008.

OBJECTIVE: To provide updated information on smoking prevalence in Italy, with a focus on demographic and socio-economic characteristics. METHOD: The survey was conducted during March-April 2008 on a sample of 3035 individuals (1459 men and 1576 women) aged 15 years or over representative of the Italian population in terms of age, sex, geographic area, and socio-economic characteristics. RESULTS: In 2008, 22.0% (95% confidence interval, CI: 20.5-23.5) of Italians described themselves as current cigarette smokers (26.4% of men, 17.9% of women); ex-smokers were 18.4% (95% CI: 17.0-19.8; 24.1% of men, 13.2% of women). By the year 2012 the number of former could exceed that of current smokers. Smoking prevalence in the young (15-24 years) was around 30% in males, and almost 20% in females. For both sexes, current smoking was less prevalent in higher (22.9% of men, 20.1% of women) than in lower educated participants (34.8% of men, 22.1% of women), and in northern (22.5% of men, 16.1% of women) than southern Italy (31.8% of men, 18.4% of women). CONCLUSION: In 2008, smoking prevalence was the lowest observed over the last 50 years, in Italy. However, part of the fall is likely due to increased under-reporting, since these survey figures are appreciably under-estimated as compared to sale data. Subjects with less privileged socio-economic characteristics should be considered target populations for tobacco control.