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Abstract Background Protective behaviors were essential for minimizing the spread of the virus during the coronavirus disease 2019 (COVID-19) pandemic. It is often assumed that awareness of bodily sensations (interoception) can improve decision-making and facilitate adaptive behavior. Objective This paper investigates cross-sectional and longitudinal relationships between different aspects of self-reported interoception, trait anxiety, COVID-related worry, and health protective behaviors. Methods The study was conducted on a community sample of 265 adults. The two data collection phases took place online, before (baseline) and during the second wave of the COVID-19 pandemic in Hungary. Results Contrary to our expectations, neither cross-sectional nor longitudinal associations were found between protective behaviors and indicators of self-reported interoception. However, worry at baseline predicted protective behaviors during the second wave, even after controlling for socio-economical characteristics and protective behaviors at baseline. Conclusion Our results highlight the adaptivity of health-related worry when behavioral steps to avoid threats are known and available. Also, higher level of perceived interoception did not appear to be health protective under these circumstances.

There are a number of questionnaires assessing the self-reported trait-like aspect of interoception, also called interoceptive sensibility (ISb). Based on the varying purposes of their development and characteristics, however, it is not likely that they assess exactly the same construct. In a community sample of 265 adults, we examined this assumption for three commonly used questionnaires of ISb, namely the Body Awareness subscale of the Body Perception Questionnaire (BPQ-BA), the Body Awareness Questionnaire (BAQ), and the eight subscales of Multidimensional Assessment of Interoceptive Awareness (MAIA). We investigated their associations, and their relation to positive and negative affect and somatosensory amplification. According to the results of correlation analysis, BPQ-BA, BAQ and MAIA were partly unrelated to each other, partly showed weak to moderate positive associations. Also, differences with respect to their association with positive and negative affect were found. These findings suggest that the investigated questionnaires cannot be used interchangeably to assess the subjective aspect of interoception, and the term ISb is not appropriately defined.

Interoception in the broader sense refers to the perception of internal states, including the perception of the actual state of the internal organs (visceroception) and the motor system (proprioception). Dimensions of interoception include (1) interoceptive accuracy, i.e., the ability to sense internal changes assessed with behavioral tests, (2) confidence rating with respect to perceived performance in an actual behavioral test, and (3) interoceptive sensibility, i.e., the self-reported generalized ability to perceive body changes. The relationship between dimension of cardioceptive and proprioceptive modalities and their association with affect are scarcely studied. In the present study, undergraduate students (N = 105, 53 males, age: 21.0 ± 1.87 years) filled out questionnaires assessing positive and negative affect (Positive and Negative Affect Schedule), interoceptive sensibility (Body Awareness Questionnaire), and body competence (Body Competence Scale of the Body Consciousness Questionnaire). Following this, they completed a behavioral task assessing cardioceptive accuracy (the mental heartbeat tracking task by Schandry) and two tasks assessing proprioceptive accuracy with respect to the tension of arm flexor muscles (weight discrimination task) and the angular position of the elbow joint (joint position reproduction task). Confidence ratings were measured with visual analog scales after the tasks. With the exception of a weak association between cardioceptive accuracy and the respective confidence rating, no associations between and within modalities were found with respect to various dimensions of interoception. Further, the interoceptive dimensions were not associated with state and trait positive and negative affect and perceived body competence. In summary, interoceptive accuracy scores do not substantially contribute to conscious representations of cardioceptive and proprioceptive ability. Within our data, non-pathological affective states (PANAS) are not associated with the major dimensions of interoception for the cardiac and proprioceptive modalities.

Since the pivotal studies of neurophysiologists in the early 20th century, research on brain functions in non-human primates has provided valuable insights into the neural mechanisms subserving neurological function. By using data acquired on non-human primates as a reference, important progress in knowledge of the human brain and its functions has been achieved. The translational impact allowed by this scientific effort must be recognized in the implementation of the current surgical techniques particularly in support of the neurosurgical approach to brain tumors. In the surgical treatment of brain tumors, the ability to maximally extend the resection allows an improvement in overall survival, progression-free survival, and quality of life of patients. The main goal, and, at the same time, the main challenge, of oncological neurological surgery is to avoid permanent neurological deficit while reaching maximal resection, particularly when the tumor infiltrates the neural network subserving motor functions. Brain mapping techniques were developed using neurophysiological probes to identify the areas and tracts subserving sensorimotor function, ensuring their preservation during the resection. During the last 20 years, starting from the classical “Penfield” technique, brain mapping has been progressively implemented. Among the major advancements was the introduction of high-frequency direct electrical stimulation. Its refinement, along with the complementary use of low-frequency stimulation, allowed a further refinement of stimulation protocols. In this narrative review, we propose an analysis of the process through which the knowledge acquired through experiments on non-human primates influenced and changed the current approach to neurosurgical procedures. We then describe the main brain mapping techniques used in the resection of tumors located within sensorimotor circuits. We also detail how these techniques allowed the acquisition of new data on the properties of areas and tracts underlying sensorimotor control, in turn fostering the design of new tools to navigate within cortical and subcortical areas, that were before deemed to be “sacred and untouchable.”

Introduction Lafora disease (LD) is an ultrarare fatal progressive myoclonic epilepsy, causing drug-resistant epilepsy, myoclonus and psychomotor deterioration. LD is caused by mutations in EPM2A or NHLRC1, which lead to the accumulation of polyglucosans in the brain and neurodegeneration. There are no approved treatments for LD. VAL-1221 is a fusion protein comprising the Fab portion of a cell-penetrating antibody and recombinant human acid alpha glucosidase, and has demonstrated an ability to clear polyglucosans. We hypothesise that intravenous infusion of VAL-1221 might be able to degrade cerebral polyglucosans and stabilise or improve disease outcomes. The aim of this study is to assess the safety and preliminary efficacy of VAL-1221 in patients with LD.Methods and analysis The study is a phase 2, single-arm, open-label, baseline-controlled clinical trial which will be conducted in a single investigational study centre in Italy, namely the sponsor ‘IRCCS Istituto delle Scienze Neurologiche di Bologna—Azienda USL di Bologna’. The study will enrol six genetically confirmed patients with mid- to late-stage LD. The global duration of the study for each participant will be 18 months, including screening period, open-label treatment (12 months) and follow-up period. VAL-1221 20 mg/kg will be administered as an intravenous infusion every week for 3 weeks, then every other week. Patients will undergo full clinical assessments at baseline, at an intermediate and at the end-of-treatment visit. The primary objective is to evaluate the safety. The exploratory efficacy endpoints will be related to epilepsy, neuropsychological and motor functions, global assessment and disease burden, in addition to biomarkers. Statistical analyses will be primarily descriptive.Ethics and dissemination The study protocol was approved by the local ethics committee (number 232-2023-FARM-AUSLBO-23020, 22 March 2023). The results of this study will be disseminated by the investigators through presentations at international scientific conferences and reported in peer-reviewed scientific journals.Trial registration number European Union Clinical Trials Register (EudraCT 2023-000185-34).

ObjectiveSexual functioning is a multifaceted aspect of human life that can be profoundly affected in patients with glioma. Most frequent symptoms include reduced sexual desire, difficulties in sexual arousal, or low satisfaction. Such symptoms may cause distress or interpersonal difficulties, inevitably resulting in negative outcomes on different domains of patients’ quality of life. Despite this, sexuality is rarely addressed by medical staff and remains understudied. An important question still unanswered is whether sexual dysfunctions in glioma patients correlate with features of the tumor itself, with its treatment, or with the secondary effects of the tumor on the patient’s psychological status. To answer this question, the present study aims to investigate the incidence of sexual life impairments in a very large population of patients with low- and high-grade gliomas, focusing on demographic, clinical, and treatment factors associated with their occurrence and developments.MethodsA total of 148 patients treated for glioma were evaluated for sexual functioning, i.e., sexual dysfunction (SD), relationship status (RS), intercourse frequency (IF), and sexual satisfaction (SS), by using a specific anonymous questionnaire. Descriptive statistics were utilized to investigate participant characteristics and to evaluate the occurrence of sexual problems. Chi-squared tests were performed to detect the association between “SS” or “IF” and different clinical/demographic factors as well as between “SS” or “IF” and the “subjective–personal skills judgment”.ResultsResults showed no difference between male and female patients, a very low frequency (1.4%) of SD, but a consistent percentage (25%) of subjective deterioration in sexual wellbeing. Notably, 24% of patients reported to have interrupted their relationship after the diagnosis. Chi-squared analyses reveal an association between adjuvant treatments (chemotherapy and radiotherapy) and reduction of IF. Interestingly, “SS” or “IF” was not associated with demographic, clinical, or histomolecular factors.ConclusionOur study showed that sexual problems in glioma patients are not uncommon, and they are especially linked to SS, RS, and IF. Specifically, intercourse frequency reduction is associated with the adjuvant treatments. Results highlight the need for improved assessment strategies and interventions tailored to the unique needs of brain tumor patients.

Abstract Narcolepsy type 1 (NT1) is a chronic neurological disorder characterized by symptoms such as excessive daytime sleepiness, sudden sleep episodes, disrupted nocturnal sleep, cataplexy, sleep paralysis, and hypnagogic hallucinations, which significantly impact the overall well-being and quality of life of individuals. While psychological factors have gained attention, there is limited research on the coping strategies employed by patients with NT1 and their association with quality of life. This study aimed to compare coping strategies in patients with NT1 and controls, as well as assess the relationship between coping strategies and quality of life in patients with NT1. A total of 122 individuals diagnosed with NT1 and 138 controls were enrolled in this cross-sectional study. Participants completed questionnaires assessing coping strategies and health-related quality of life. A Mann–Whitney U test was conducted to compare the use of different coping strategies by patients with NT1 and controls. Spearman's rho correlation was performed to examine the association between coping strategies and quality of life in the NT1 group. Results showed that patients with NT1 exhibited differences in the use of coping strategies compared to controls. They reported lower use of active coping, planning, instrumental, and emotional social support, and higher use of behavioral and mental disengagement. Denial and behavioral disengagement were significantly and negatively associated with quality of life. Identifying coping strategies and their association with quality of life may aid in the development of tailored interventions aimed at improving the adoption of effective coping strategies and reducing the use of maladaptive coping strategies.

The full potential of the Internet of Musical Things (IoMusT) paradigm can be fully unleashed only in the presence of widespread, reliable wireless connectivity, allowing musicians to connect their smart instruments (almost) anywhere they are. For this reason, we propose a realistic, end-to-end communication architecture for a IoMusT system based on public fifth-generation (5G) mobile networks that considers a networked music performance use case, and we introduce a model for the resulting system. We define high-level service requirements and key performance indicators for the network’s connect-compute architecture. We evaluate our solution via system-level simulations using the well-known 5G-LENA/ns3 and Simu5G/OMNeT++ frameworks. We found that operating 6 or more IoMusT devices over a fourth-generation (4G) network results in a worst-case latency well over 20 ms for more than 90% of the packet transmissions, while losing more than 10% of packets. On the other hand, operating the same number of devices over a 5G network reduces the latency significantly. After testing our findings both in single-cell and in multi-cell scenarios, assuming a transient in the upgrade of mobile network infrastructures from 4G to 5G, we consider a E-UTRA-NR dual connectivity (EN-DC) scenario, where a 5G base station serves a subset of the users of a 4G cell. Furthermore, we conducted a user study where musicians were asked to assess their playing experience during simulated 4G- and 5G-based networked music performances. The results of the simulations and of the user study consistently indicate that the use of 5G technology improves performance significantly, and advocate the need for a 5G framework to fully support the IoMusT.

Networked Music Performances (NMPs) involve geographically-displaced musicians performing together in real-time. To date, scarce research has been conducted on how to integrate NMP systems with immersive audio rendering techniques able to enrich the musicians’ perception of sharing the same acoustic environment. In addition, the use of wireless technologies for NMPs has been largely overlooked. In this paper, we propose two architectures for Immersive Networked Music Performances (INMPs), which differ for the physical positions of the computing blocks constituting the 3D audio toolchain. These architectures leverage a backend specifically conceived to support remote musical practices via Software Defined Networking methods, and take advantage of the orchestration, slicing, and Multi-access Edge Computing (MEC) capabilities of 5G. Moreover, we illustrate how to integrate in the architectures machine learning algorithms for network traffic prediction and audio packet loss concealment. Traffic predictions at multiple time scales are utilized to achieve an optimized placement of Virtual Network Functions hosting audio mixing and processing functionalities within the available MEC sites, depending on the users’ geographical locations and current network load conditions. An analysis of the technical requirements for INMPs using the two architectures is provided, along with their performance assessment conducted via simulators.

Excessive daytime sleepiness (EDS) and insomnia (IN) complaints represent the most common sleep/wake disorders. Currently, the specific needs of these patients and their relatives, as well as the overall socio-economic burden of IN and EDS remains widely unexplored. This pilot study to be carried out in Switzerland is a retro- and prospective, national, one-center cohort observational study for the systematic evaluation of the burden of EDS and IN and its evolution 12 months after the first assessment. Patient recruitment will be organized through 7–8 primary care providers (primary/general care practitioners and pharmacies). Primary outcomes are the prevalence of EDS/IN in the primary care setting and the association between EDS/IN with health-related quality of life (QOL) as assessed with the established instruments. Secondary outcomes are the association between EDS/IN with the presence of comorbidities, number of injuries/accidents, and number of sick/leave days for the subgroup of working subjects. Calculation of direct per-patient costs will be undertaken to analyze the economic implications of sleep/wake disorders, providing valuable insights into the financial burden experienced by affected individuals within the healthcare system. This research will provide information on the feasibility of such a study and inform on aspects of the QOL most associated with EDS/IN. Based on this pilot project, a European multicenter study on the burden of sleep/wake disorders will be conducted by the European Academy of Neurology.

Abstract Background Lafora disease (LD) is a fatal form of progressive myoclonic epilepsy caused by biallelic pathogenic variants in EPM2A or NHLRC1. With a few exceptions, the influence of genetic factors on disease progression has yet to be confirmed. We present a systematic review and meta-analysis of the known pathogenic variants to identify genotype–phenotype correlations. Methods We collected all reported cases with genetically-confirmed LD containing data on disease history. Pathogenic variants were classified into missense (MS) and protein-truncating (PT). Three genotype classes were defined according to the combination of the variants: MS/MS, MS/PT, and PT/PT. Time-to-event analysis was performed to evaluate survival and loss of autonomy. Results 250 cases described in 70 articles were included. The mutated gene was NHLRC1 in 56% and EPM2A in 44% of cases. 114 pathogenic variants (67 EPM2A; 47 NHLRC1) were identified. The NHLRC1 genotype PT/PT was associated with shorter survival [HR 2.88; 95% CI 1.23–6.78] and a trend of higher probability of loss of autonomy [HR 2.03, 95% CI 0.75–5.56] at the multivariable Cox regression analysis. The population carrying the homozygous p.Asp146Asn variant of NHLRC1 genotype was confirmed to have a more favourable prognosis in terms of disease duration. Conclusions This study demonstrates the existence of prognostic genetic factors in LD, namely the genotype defined according to the functional impact of the pathogenic variants. Although the reasons why NHLRC1 genotype PT/PT is associated with a poorer prognosis have yet to be fully elucidated, it may be speculated that malin plays a pivotal role in LD pathogenesis.

The radiomic analysis of the tissue surrounding colorectal liver metastases (CRLM) enhances the prediction accuracy of pathology data and survival. We explored the variation of the textural features in the peritumoural tissue as the distance from CRLM increases. We considered patients with hypodense CRLMs >10 mm and high-quality computed tomography (CT). In the portal phase, we segmented (1) the tumour, (2) a series of concentric rims at a progressively increasing distance from CRLM (from one to ten millimetres), and (3) a cylinder of normal parenchyma (Liver-VOI). Sixty-three CRLMs in 51 patients were analysed. Median peritumoural HU values were similar to Liver-VOI, except for the first millimetre around the CRLM. Entropy progressively decreased (from 3.11 of CRLM to 2.54 of Liver-VOI), while uniformity increased (from 0.135 to 0.199, p < 0.001). At 10 mm from CRLM, entropy was similar to the Liver-VOI in 62% of cases and uniformity in 46%. In small CRLMs (≤30 mm) and responders to chemotherapy, normalisation of entropy and uniformity values occurred in a higher proportion of cases and at a shorter distance. The radiomic analysis of the parenchyma surrounding CRLMs unveiled a wide halo of progressively decreasing entropy and increasing uniformity despite a normal radiological aspect. Underlying pathology data should be investigated.

IntroductionThe sensorimotor integrations subserving object-oriented manipulative actions have been extensively investigated in non-human primates via direct approaches, as intracortical micro-stimulation (ICMS), cytoarchitectonic analysis and anatomical tracers. However, the understanding of the mechanisms underlying complex motor behaviors is yet to be fully integrated in brain mapping paradigms and the consistency of these findings with intraoperative data obtained during awake neurosurgical procedures for brain tumor removal is still largely unexplored. Accordingly, there is a paucity of systematic studies reviewing the cross-species analogies in neural activities during object-oriented hand motor tasks in primates and investigating the concordance with intraoperative findings during brain mapping. The current systematic review was designed to summarize the cortical and subcortical neural correlates of object-oriented fine hand actions, as revealed by fMRI and PET studies, in non-human and human primates and how those were translated into neurosurgical studies testing dexterous hand-movements during intraoperative brain mapping.MethodsA systematic literature review was conducted following the PRISMA guidelines. PubMed, EMBASE and Web of Science databases were searched. Original articles were included if they: (1) investigated cortical activation sites on fMRI and/or PET during grasping task; (2) included humans or non-human primates. A second query was designed on the databases above to collect studies reporting motor, hand manipulation and dexterity tasks for intraoperative brain mapping in patients undergoing awake brain surgery for any condition. Due to the heterogeneity in neurosurgical applications, a qualitative synthesis was deemed more appropriate.ResultsWe provided an updated overview of the current state of the art in translational neuroscience about the extended frontoparietal grasping-praxis network with a specific focus on the comparative functioning in non-human primates, healthy humans and how the latter knowledge has been implemented in the neurosurgical operating room during brain tumor resection.DiscussionThe anatomical and functional correlates we reviewed confirmed the evolutionary continuum from monkeys to humans, allowing a cautious but practical adoption of such evidence in intraoperative brain mapping protocols. Integrating the previous results in the surgical practice helps preserve complex motor abilities, prevent long-term disability and poor quality of life and allow the maximal safe resection of intrinsic brain tumors.

The essay develops an aesthetic of the threshold from an analysis of the artistic collaboration between Werner Ruhnau and Yves Klein for the realisation of the Musiktheater im Revier in Gelsenkirchen. The threshold is a figure of thought that stands for the artistic choice to create zones of interaction between work and spectator, in which exchanges of roles and production of meaning take place. The aesthetics of the threshold in Ruhnau manifests itself through the architectural design of playful theatrical spaces in which the theatre audience can stage new identities. In Klein, the threshold becomes a meditative space, through which the subject trains his faculties of feeling and making sense. In the “Verfransung” (Adorno) between the strategies of Ruhnau and Klein, the theatre becomes the threshold for an interaction between public space and sensibility.

Abstract Background To evaluate the effects on ocular surface signs and symptoms of serial sessions of heating and vibrating eye mask followed by intense pulsed light (IPL) therapy for the treatment of dry eye disease owing to meibomian gland dysfunction (MGD). Methods Consecutive patients with MGD whose signs and symptoms were not satisfactorily controlled with conventional therapy were included. Patients received 3 treatments performed at day 1, 15, and 45 incorporating a session with a newly-developed eye mask (Activa, SBS Sistemi, Turin, Italy) immediately followed by IPL therapy (E > Eye device, E-Swin, Paris, France). Patients were examined before the first session (T0) and 30 days after the last session (T1) for the measurement of: noninvasive break-up time (NIBUT); lipid layer thickness (LLT); tear meniscus height (TMH); meibomian gland loss (MGL); tear osmolarity. Ocular discomfort symptoms were ascertained by ocular surface disease index (OSDI) questionnaire. Results Thirty patients were ultimately included in the study. At T1, all objective ocular surface parameters improved significantly, except for TMH: NIBUT and LLT increased from 6.4 ± 1.7 to 8.6 ± 1.7 s and from 57.7 ± 15.5 to 81.3 ± 12.0 μm (all P

Summary: Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84–1.29], p = 0.711 and HR 1.18 [0.95–1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79–1.17], p = 0.67 and HR 1.48 [1.16–1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02–1.74], p = 0.037) and OS (HR 1.26 [1.03–1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3–3.52], p

BackgroundAtaxia is a rare neurological condition causing a deficit in the coordination of motor activities, preventing the fluidity of movements. Children with ataxia may show several different ataxic signs, along with difficulties in walking autonomously and ataxic gait often associated with trunk instability. Ataxic signs can be either acute or chronic, and in either case, the diagnosis can be extremely complex. Symptoms and their etiology are often widely heterogeneous, even within the same condition.MethodsThe guideline was developed based on the methodology defined by the Methodological Handbook of the Italian National Guideline System (SNLG) and was reported following the AGREE-II checklist. The SNLG methodology required the adoption of the GRADE approach for the whole development process. To facilitate the implementation of the contents and recommendations from the guideline, two care pathways were developed based on the NICE and the European Pathway Association (EPA) models.ResultsThe guideline included 28 clinical questions, 4 on the identification and management of acute ataxias, and 24 on the diagnosis and management of chronic ataxias. The document included 44 recommendations, 37 clinical recommendations, and 7 recommendations for research.ConclusionThe working group, despite the lack and methodological limitations of the evidence, deemed as essential to provide indications and recommendations, in particular in some clinically relevant areas. The care pathway was produced as a tool to facilitate the implementation of the contents and recommendations. The interactive version of the pathway is available on the SNLG website along with a leaflet dedicated to families and caregivers.

ObjectiveSafe resection of gliomas involving motor pathways in asleep-anesthesia requires the combination of brain mapping, to identify and spare essential motor sites, and continuous monitoring of motor-evoked potentials (MEPs), to detect possible vascular damage to the corticospinal tract (CST). MEP monitoring, according to intraoperative neurophysiology societies, is generally recommended by transcranial electrodes (TES), and no clear indications of direct cortical stimulation (DCS) or the preferential use of one of the two techniques based on the clinical context is available. The main aim of the study was to identify the best technique(s) based on different clinical conditions, evaluating the efficacy and prognostic value of both methodologies.MethodsA retrospective series of patients with tumors involving the motor pathways who underwent surgical resection with the aid of brain mapping and combined MEP monitoring via TES and DCS was evaluated. Irreversible MEP amplitude reduction (>50% compared to baseline) was used as an intraoperative warning and correlated to the postoperative motor outcome. Selectivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were computed for both techniques.ResultsFour hundred sixty-two patients were retrospectively analyzed, and only 1.9% showed a long-term motor impairment. Both TES and DCS obtained high specificity and NPV for the acute and 1-month motor deficit. Sensitivity was rather low for the acute deficit but excellent considering the 1-month follow-up for both techniques. DCS was extremely reliable in predicting a postoperative motor decline (PPV of 100% and 90% for acute and long-term deficit, respectively). Conversely, TES produced a high number of false-positive results, especially for long-term deficits (65, 87.8% of all warnings) therefore obtaining poor PPV values (18% and 12% for acute and 1-month deficits, respectively). TES false-positive results were significantly associated with parietal tumors and lateral patient positioning.ConclusionsData support the use of mapping and combined monitoring via TES and DCS. The sole TES monitoring is reliable in most procedures but not in parietal tumors or those requiring lateral positioning. Although no indications are available in international guidelines, DCS should be recommended, particularly for cases approached by a lateral position.

Abstract Background Lafora disease (LD) is a rare fatal autosomal recessive form of progressive myoclonus epilepsy. It affects previously healthy children or adolescents, causing pharmacoresistant epilepsy, myoclonus and severe psychomotor deterioration. This work aims to describe the clinical course of LD and identify predictors of outcome by means of a prognostic systematic review with individual participant data meta-analysis. Methods A search was conducted on MEDLINE and Embase with no restrictions on publication date. Only studies reporting genetically confirmed LD cases were included. Kaplan–Meier estimate was used to assess probability of death and loss of autonomy. Univariable and multivariable Cox regression models with mixed effects (clustered survival data) were performed to evaluate prognostic factors. Results Seventy-three papers describing 298 genetically confirmed LD cases were selected. Mean age at disease onset was 13.4 years (SD 3.7), with 9.1% aged ≥ 18 years. Overall survival rates in 272 cases were 93% [95% CI 89–96] at 5 years, 62% [95% CI 54–69] at 10 years and 57% [95% CI 49–65] at 15 years. Median survival time was 11 years. The probability of loss of autonomy in 110 cases was 45% [95% CI 36–55] at 5 years, 75% [95% CI 66–84] at 10 years, and 83% [95% CI 74–90] at 15 years. Median loss of autonomy time was 6 years. Asian origin and age at onset

Abstract Background Narcolepsy is a rare chronic sleep disorder that typically begins in youth. Excessive daytime sleepiness is the main disabling symptom, but the disease is often associated with severe endocrine-metabolic and psychosocial issues, worsened by a long diagnostic delay, requiring a multidisciplinary approach. The scarcity of reference Sleep Centres forces the patient and family to travel for seeking medical consultations, increasing the economic and psychosocial burden of the disease. Growing evidence suggests that Telemedicine may facilitate patient access to sleep consultations and its non-inferiority in terms of patient satisfaction, adherence to treatment, and symptom improvement for sleep disorders. However, Telemedicine clinical and economic benefits for patients with narcolepsy are still unknown. Methods TENAR is a two-part project, including: 1. a cross-sectional study (involving 250 children and adults with suspected narcolepsy) evaluating the accuracy of Teletriage (i.e., a synchronous live interactive sleep assessment through a Televisit) for narcolepsy diagnosis compared to the reference standard; and 2. a two-arm, parallel, open randomized controlled trial (RCT) to demonstrate the non-inferiority of the multidisciplinary care of narcolepsy through Televisits versus standard care. In this RCT, 202 adolescents (> 14 y.o.) and adults with narcolepsy will be randomly allocated (1:1 ratio) either to Televisits via videoconference or to standard in-person outpatient follow-up visits (control arm). The primary outcome is sleepiness control (according to the Epworth Sleepiness Scale). Secondary outcomes are other symptoms control, compliance with treatment, metabolic control, quality of life, feasibility, patient and family satisfaction with care, safety, and disease-related costs. At baseline and at 12 months, patients will undergo neurologic, metabolic, and psychosocial assessments and we will measure primary and secondary outcomes. Primary outcomes will be also measured at 6 months (remotely or in person, according to the arm). Discussion TENAR project will assess, for the first time, the feasibility, accuracy, efficacy and safety of Telemedicine procedures applied to the diagnosis and the multidisciplinary care of children and adults with narcolepsy. The study may be a model for the remote management of other rare disorders, offering care access for patients living in areas lacking medical centres with specific expertise. Trial registration Number of the Tele-multidisciplinary care study NCT04316286 . Registered 20 March 2020.

My contribution aims to describe an aesthetics of gesture based on Giorgio Agamben’s and Jean-Luc Nancy’s reflections about the relationship between gestures (as means of non-verbal communication) and medial-technological forms of production of sense. In the second part of my study I will analyse an installation of the artistic collective Studio Azzuro with the title In Principio (e poi) through the aforementioned aesthetics of gesture. Il presente studio tenta di delineare un’estetica del gesto a partire da alcune riflessioni di Giorgio Agamben e Jean-Luc Nancy circa la relazione tra i gesti (in quanto mezzi per la comunicazione non-verbale) e le forme tecnico-mediali di produzione di senso. Nella seconda parte del mio contributo analizzerò attraverso tale estetica del gesto un’installazione del collettivo artistico Studio Azzurro dal titolo In Principio (e poi).

BackgroundThe indirect impact of the COVID-19 epidemic on major clinical outcomes of people with Parkinson's disease (PD) or other parkinsonism is unknown.ObjectivesThe study aimed to (1) describe changes in healthcare services during the first epidemic bout in people with PD or parkinsonism; (2) compare the occurrence of hospitalization for any PD-related major clinical outcomes in 2020 with 2019; (3) investigate the factors, including changes in healthcare services, associated with major clinical outcomes and death.MethodsAll healthcare services of the province of Bologna and major clinical outcomes were assessed through a record linkage study (ParkLink Bologna) using clinical data and health databases. Same analyses were performed in a random cohort of controls matched for age, sex, district of residence, and comorbidities with the ParkLink cohort (ratio of 1:10).ResultsA cohort of subjects with PD (759) or other parkinsonism (192) was included together with a cohort of controls (9,226). All indicators of healthcare services dropped at least below 50% during the lockdown period in all cohorts, mostly impacting physiotherapy in people with PD (−93%, 95% CI 88–96%). In 2020, compared to 2019, a three-fold risk of major injuries (RR 3.0, 95% CI 1.5–6.2) and infections (RR 3.3, 95% CI 1.5–7.2), excluding COVID-19, was observed only in people with PD, and neither in people with parkinsonism nor in controls. Decreased physiotherapy was associated with the occurrence of at least one major clinical outcome (OR 3.3, 95% CI 1.1–9.8) in people with PD. Experiencing at least one major clinical outcome was the strongest risk factor for death (OR 30.4, 95% CI 11.1–83.4) in people with PD.ConclusionsDuring the first COVID-19 epidemic peak, healthcare services were drastically reduced in a province of northern Italy, regardless of the disease condition. However, compared to 2019, in 2020, only people with PD had a higher risk of major clinical outcomes, that were associated with higher mortality. Strategies to maintain physical activity in people with PD should be implemented in possible future health emergencies.

In primates, the parietal cortex plays a crucial role in hand-object manipulation. However, its involvement in object manipulation and related hand-muscle control has never been investigated in humans with a direct and focal electrophysiological approach. To this aim, during awake surgery for brain tumors, we studied the impact of direct electrical stimulation (DES) of parietal lobe on hand-muscles during a hand-manipulation task (HMt). Results showed that DES applied to fingers-representation of postcentral gyrus (PCG) and anterior intraparietal cortex (aIPC) impaired HMt execution. Different types of EMG-interference patterns were observed ranging from a partial (task-clumsy) or complete (task-arrest) impairment of muscles activity. Within PCG both patterns coexisted along a medio (arrest)–lateral (clumsy) distribution, while aIPC hosted preferentially the task-arrest. The interference patterns were mainly associated to muscles suppression, more pronounced in aIPC with respect to PCG. Moreover, within PCG were observed patterns with different level of muscle recruitment, not reported in the aIPC. Overall, EMG-interference patterns and their probabilistic distribution suggested the presence of different functional parietal sectors, possibly playing different roles in hand-muscle control during manipulation. We hypothesized that task-arrest, compared to clumsy patterns, might suggest the existence of parietal sectors more closely implicated in shaping the motor output.

Introduction Epilepsy is a chronic condition requiring consistent follow-up aimed at seizure control, and monitoring of anti-seizure medication (ASM) levels and side effects. Telemedicine (TM) offers invaluable support to patient follow-up, guaranteeing the prompt availability of a team of experts for persons with epilepsy (PWE) widely distributed across the country. Although many health institutions have endorsed the use of TM, robust data on effectiveness, safety and costs of TM applied to epilepsy are lacking. TELEmedicine for EPIlepsy Care (TELE-EPIC) will evaluate the effectiveness of video consultation (VC) via TM compared with usual care (UC) for the monitoring of PWE (TELE-EPIC_RCT). Moreover, TELE-EPIC will apply an innovative Volumetric Absorptive Microsampling (VAMS) device for quantitation of ASM through finger prick blood sampling as an alternative to venipuncture sampling (TELE-EPIC_VAMS).Methods and analysis TELE-EPIC_RCT is a multicentre, open, pragmatic two-arm randomised controlled trial prospectively including adult and paediatric outpatients with established diagnosis of epilepsy consecutively attending the Epilepsy Centres of Bologna and Rome, respectively. The primary outcome is the non-inferiority of VC on seizure control compared with UC after an 18-month follow-up. Secondary outcomes are adherence to treatment, ASM-related adverse events, quality of life, mood disorders, patient and caregiver satisfaction, safety and costs. TELE-EPIC_VAMS is a cross-validation study for blood ASM quantitation through a novel, VAMS-based device, comparing (1) VAMS versus plasma samples (reference standard method); and (2) nurse-collected versus self-collected blood by VAMS device.Ethics and dissemination The study has been approved by the local ethics committee (349-2019-SPER-AUSLBO). Complete information about the state of project, relevant events and results will be regularly updated on the project’s webpage on ClinicalTrials.gov. The project’s results and data on the potential impact of TM in epilepsy will be disseminated on social media. A closeout meeting will be convened for the communication and dissemination of the project, highlighting its main achievements and impacts.Trial registration number NCT04496310

ObjectiveAt present, it is not clear whether Mood Disorders (MD) and poor Health Related Quality of Life (HRQoL) in the glioma population correlate with features of the tumor, or rather with secondary symptoms associated with treatment. The aim of this study was to assess the prevalence of MD and decline in HRQoL in glioma patients, and to determine the main factors associated with these two variables.Methods80 patients affected by lower-grade gliomas (LGGs) and 65 affected by high-grade gliomas (HGGs) were evaluated, from admission up to 12 months after surgery, for MD, HRQoL, clinical characteristics, and cognitive functions. Independent factors associated with MD and low HRQoL were identified by using bivariate analysis.ResultsData showed that prevalence of low HRQoL was comparable in both groups during all the time points assessed (pre, 1, 3, 6 and 12 months after surgery). In contrast at 6 months following surgery, HGGs showed a higher prevalence of MD compared to LGGs;. Bivariate analysis revealed that factors associated with MD and HRQoL in LGGs and HGGs were different over the course of the disease. In LGGs, from the pre-operative period to one year post surgery, MD and low HRQOL were associated with the occurrence of cognitive deficits and, from the third month after surgery onward, they were also associated with the effect exerted by adjuvant treatments. In HGGs, MD were associated with cognitive deficits at 3 and 6 months after surgery, along with older age (65-75 years); HRQoL, in its Physical component in particular, was associated with older age only from 6 months after surgery.ConclusionFactors associated with MD and low HRQoL were different in LGGs and HGGs over the course of the disease. In LGGs the effect of adjuvant treatments was prominent in determining the prevalence of both MD and poor HRQoL from the third month after surgery onward. In HGGs, MD and HRQoL were associated with age, at 3 and 6 months after surgery. In both, the occurrence of cognitive deficits was significantly associated with MD.

Abstract Study Objectives Narcolepsy type 1 (NT1) is a chronic rare hypersomnia of central origin requiring a combination of behavioral and pharmacological treatments. During the coronavirus disease 2019 (COVID‐19) pandemic, in Italy the population was forced into a lockdown. With this study, we aimed to describe the lockdown impact on NT1 symptom management, according to different patients' working schedule. Methods In the period between 10 April and 15 May 2020, we performed routine follow‐up visits by telephone (as recommended during the COVID‐19 emergency) to 50 patients >18 years old (40% males) under stable long‐term treatment. We divided patients into three groups: unchanged working schedule, forced working/studying at home, and those who lost their job (“lost occupation”). Current sleep–wake habit and symptom severity were compared with prelockdown assessment (six months before) in the three patient groups. Results At assessment, 20, 22, and eight patients belonged to the unchanged, working/studying at home, and lost occupation groups, respectively. While in the lost occupation group, there were no significant differences compared with prepandemic assessment, the patients with unchanged schedules reported more nocturnal awakenings, and NT1 patients working/studying at home showed an extension of nocturnal sleep time, more frequent daytime napping, improvement of daytime sleepiness, and a significant increase in their body mass index. Sleep‐related paralysis/hallucinations, automatic behaviors, cataplexy, and disturbed nocturnal sleep did not differ. Conclusions Narcolepsy type 1 patients working/studying at home intensified behavioral interventions (increased nocturnal sleep time and daytime napping) and ameliorated daytime sleepiness despite presenting with a slight, but significant, increase of weight.

Purpose. To investigate the short-term effects on tear film parameters and ocular symptoms of a novel eye mask producing heat and vibration developed for the treatment of dry eye disease owing to meibomian gland dysfunction (MGD). Methods. This is a pilot study including the first 20 consecutive patients (6 males, 14 females; mean age 52.4 ± 16.8 years) who were treated with a novel eye mask producing heat (42°) and vibration (up to 20 Hz) (Activa, SBS Sistemi, Turin, Italy) for 15 minutes. The treatment incorporates 2 phases in the following chronological order: 5 minutes of heating (phase I); 10 minutes of combination of heating and vibration (phase II). Noninvasive ocular surface examination was carried out before (T0) and 30 minutes after the mask session (T1) by means of Idra (SBS Sistemi, Turin, Italy) for the measurement of noninvasive break-up time (NIBUT) and lipid layer thickness (LLT). Patients’ satisfaction after treatment was ascertained by asking the patients whether they perceived improvement from their baseline symptoms according to a 5-grade scale: none = 0; trace = 1; mild = 2; moderate = 3; high = 4. Results. All patients completed regularly the mask session and no device-related adverse events were noted. NIBUT improved significantly from T0 to T1 (from 7.2 ± 1.8 s to 8.1 ± 2.1; P = 0.014). In parallel, also LLT improved from from T0 to T1 (72.5 ± 13.9 nm to 83.1 ± 16.1; P = 0.016). Seven patients (35% of the total) had a moderate satisfaction (grade 3) while 13 patients (65%) had a high satisfaction (grade 4) with treatment. Conclusions. This eye mask represents a novel well tolerated tool in the armamentarium of MGD treatments. Thirty minutes after the session, NIBUT and LLT increased significantly; furthermore, all patients reported an improvement of discomfort symptoms with a moderate to high satisfaction with treatment.

Objectives: We explored the impact of the coronavirus disease-19 (COVID-19) emergency on the health of people with epilepsy (PwE). We also investigated their attitude toward telemedicine.Methods: The PubMed database up to September 10, 2020 was searched for questionnaire-based studies conducted in PwE during the COVID-19 emergency, and the literature retrieved was reviewed. In addition, all patients who had a telephone consultation with our center between May 7 and July 31, 2020 were invited to fill in a 57-item online questionnaire focusing on epilepsy and comorbidities, any changes in lifestyle or clinical conditions and any emergency-related problems arising during the COVID-19 emergency, and their views on telemedicine. Associations between variables were detected through X2 test and Fisher's exact test. Univariate and multivariate logistic regression models were used to evaluate the effects of different factors on clinical conditions.Results: Twelve studies met the literature search criteria. They showed that the rate of seizure worsening during the emergency ranged from 4 to 35% and was mainly correlated with epilepsy severity, sleep disturbances and COVID-19-related issues. Our questionnaire was filled in by 222 PwE or caregivers. One hundred (76.6%) reported unchanged clinical conditions, 25 (11.3%) an improvement, and 27 (12%) a deterioration. Reported clinical worsening was associated with a psychiatric condition and/or medication (OR = 12.59, p < 0.001), sleep disorders (OR = 8.41, p = 0.001), limited access to healthcare (OR = 4.71, p = 0.016), and experiencing seizures during the emergency (OR = 4.51, p = 0.007). Telemedicine was considered acceptable by 116 subjects (52.3%).Conclusions: Most PwE did not experience a significant change in their clinical conditions during the COVID-19 emergency. However, severity of epilepsy, concomitant disability, comorbid psychiatric conditions, sleep disorders and limited access to healthcare may affect their health.

Objective: The intraoperative identification and preservation of optic radiations (OR) during tumor resection requires the patient to be awake. Different tasks are used. However, they do not grant the maintenance of foveal vision during all testing, limiting the ability to constantly monitor the peripheral vision and to inform about the portion of the peripheral field that is encountered. Although hemianopia can be prevented, quadrantanopia cannot be properly avoided. To overcome these limitations, we developed an intra-operative Visual field Task (iVT) to monitor the foveal vision, alerting about the likelihood of injuring the OR during task administration, and to inform about the portion of the peripheral field that is explored. Data on feasibility and efficacy in preventing visual field deficits are reported, comparing the outcome with the standard available task (Double-Picture-Naming-Task, DPNT).Methods: Patients with a temporal and/or parietal lobe tumor in close morphological relationship with the OR, or where the resection can involve the OR at any extent, without pre-operative visual-field deficits (Humphrey) were enrolled. Fifty-four patients were submitted to iVT, 38 to DPNT during awake surgery with brain mapping neurophysiological techniques. Feasibility was assessed as ease of administration, training and mapping time, and ability to alert about the loss of foveal vision. Type and location of evoked interferences were registered. Functional outcome was evaluated by manual and Humphrey test; extent of resection was recorded. Tractography was performed in a sample of patients to compare patient anatomy with intraoperative stimulation site(s).Results: The test was easy to administer and detected the loss of foveal vision in all cases. Stimulation induced visual-field interferences, detected in all patients, classified as detection or discrimination errors. Detection was mostly observed in temporal tumors, discrimination in temporo-parietal ones. Immediate visual disturbances in DPNT group were registered in 84 vs. 24% of iVT group. At 1-month Humphrey evaluation, 26% of iVT vs. 63% of DPNT had quadrantanopia (32% symptomatic); 10% of DPNT had hemianopia. EOR was similar. Detection errors were induced for stimulation of OR; discrimination also for other visual processing tract (ILF).Conclusion: iVT was feasible and sensitive to preserve the functional integrity of the OR.

Diagnostic tests are used to determine anomalies in complex systems such as organisms or built structures. Once a set of tests is performed, the experts interpret their results and make decisions based on them. This process is named diagnostic reasoning. In diagnostic reasoning a decision is established by using both rules and general knowledge on the tests and the domain. The artificial intelligence community has focused on devising and automating different methods of diagnosis for medicine and engineering, but, to the best of our knowledge, the decision process in logical terms has not yet been investigated thoroughly. The automation of the diagnostic process would be helpful in a number of contexts, in particular when the number of test sets to make decision is too wide to be dealt with manually. To tackle such challenges, we shall study logical frameworks for diagnostic reasoning, automation methods and their computational properties and technologies implementing these methods. In this paper, we present the formalization of a hybrid reasoning framework T L that hosts tests and deduction rules on tests, and an algorithm that transforms a T L theory into defeasible logic, for which an implemented automated deduction technology (called Spindle) exists. We evaluate the methodology by means of a real-world example related to the Open Web Application Security Project requisites. The full diagnostic process is driven from the definition of the issue to the decision.

Ocular surgery encompasses a wide range of procedures, including surgery of the tear ducts, eyelid, cornea and conjunctiva, lens, ocular muscle, and vitreoretinal and iris surgery. Operations are also performed for the removal of tumors, repairs of ocular trauma and, finally, corneal transplantation. Antibiotic prophylaxis for the prevention of surgical site infections (SSIs) in ocular surgery is a complex field in which shared lines of action are absent. In light of the scarcity of shared evidence in the use of ocular antimicrobial prophylaxis for the pediatric population, this consensus document aims to provide clinicians with a series of recommendations on antimicrobial prophylaxis for patients of neonatal and pediatric age undergoing eye surgery. The following scenarios are considered: (1) intraocular surgery; (2) extraocular surgery; (3) ocular trauma; (4) ocular neoplasm; (5) ocular surface transplantations; (6) corneal grafts. This work has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies and represents, in our opinion, the most complete and up-to-date collection of recommendations regarding clinical actions in the peri-operative environment in eye surgery. The application of uniform and shared protocols aims to improve surgical practice, through the standardization of procedures, with a consequent reduction of SSIs, also limiting the phenomenon of antimicrobial resistance.

Biliary tumors are rare diseases with major clinical unmet needs. Standard imaging modalities provide neither a conclusive diagnosis nor robust biomarkers to drive treatment planning. In several neoplasms, texture analyses non-invasively unveiled tumor characteristics and aggressiveness. The present manuscript aims to summarize the available evidence about the role of radiomics in the management of biliary tumors. A systematic review was carried out through the most relevant databases. Original, English-language articles published before May 2021 were considered. Three main outcome measures were evaluated: prediction of pathology data; prediction of survival; and differential diagnosis. Twenty-seven studies, including a total of 3605 subjects, were identified. Mass-forming intrahepatic cholangiocarcinoma (ICC) was the subject of most studies (n = 21). Radiomics reliably predicted lymph node metastases (range, AUC = 0.729–0.900, accuracy = 0.69–0.83), tumor grading (AUC = 0.680–0.890, accuracy = 0.70–0.82), and survival (C-index = 0.673–0.889). Textural features allowed for the accurate differentiation of ICC from HCC, mixed HCC-ICC, and inflammatory masses (AUC > 0.800). For all endpoints (pathology/survival/diagnosis), the predictive/prognostic models combining radiomic and clinical data outperformed the standard clinical models. Some limitations must be acknowledged: all studies are retrospective; the analyzed imaging modalities and phases are heterogeneous; the adoption of signatures/scores limits the interpretability and applicability of results. In conclusion, radiomics may play a relevant role in the management of biliary tumors, from diagnosis to treatment planning. It provides new non-invasive biomarkers, which are complementary to the standard clinical biomarkers; however, further studies are needed for their implementation in clinical practice.

The development of awake intraoperative brain-mapping procedures for resection of brain tumors is of growing interest in neuroscience, because it enables direct testing of brain tissue, previously only possible in non-human primates. In a recent study performed in this setting specific effects can be induced by direct electrical stimulation on different sectors of premotor cortex during the execution of a hand manipulation task. Specifically, direct electrical stimulation applied on a dorsal sector of precentral cortex led to an increase in motor unit recruitment in hand muscles during execution of a hand manipulation task (Recruitment sector). The opposite effect was elicited when electrical stimulation was delivered more ventrally on the precentral cortex (Suppression sector). We studied whether the different effects on motor behavior induced by direct electrical stimulation applied on the two sites of the precentral cortex underlie differences in their functional connectivity with other brain areas, measured using resting state fMRI. Using healthy adults scanned as part of the Human Connectome Project, we computed the functional connectivity of each sector used as seeds. The functional connectivity patterns of the two intraoperative seeds was similar but cross-comparison revealed that the left and right Recruitment sectors had stronger functional connections with the hand region of the sensorimotor cortex, while the right Suppression region displayed stronger functional connectivity with a bilateral set of parieto-frontal areas crucial for the integration of perceptual and cognitive hand-related sensorimotor processes required for goal-related hand actions. Our results suggest that analyzing data obtained in the intraoperative setting with resting state functional magnetic resonance imaging in healthy brains can yield useful insight into the roles of different premotor sectors directly involved in hand-object interaction.

Purpose. To evaluate the diagnostic performance of a novel noninvasive automated workup employed for the diagnosis of dry eye disease (DED). Methods. One hundred patients with mild to moderate DED and 100 matched control subjects were enrolled in this cross-sectional study. Ocular surface examinations were carried out by means of IDRA Plus (SBM Sistemi, Turin, Italy), which allows the automated evaluation of noninvasive breakup time (NIBUT), lipid layer thickness (LLT), tear meniscus height (TMH), infrared meibography for the measurement of meibomian gland loss (MGL), and blinking analysis. Continuous variables were compared between patients with DED and controls by using the Mann–Whitney U test. The area under the curve (AUC) of receiver operating characteristic curves was calculated. The correlations between ocular surface parameters were evaluated with Pearson correlation analysis. Results. Patients with DED showed significantly lower values of NIBUT, LLT, and TMH compared to controls (6.9 ± 2.5 vs 10.4 ± 2.4 s, P 0.05). NIBUT had the highest diagnostic power (AUC = 0.841, sensitivity = 0.89, and specificity = 0.69), followed by LLT (AUC = 0.621, sensitivity = 0.89, and specificity = 0.55), TMH (AUC = 0.606, sensitivity = 0.57, and specificity = 0.63), blink analysis (AUC = 0.533, sensitivity = 0.48, and specificity = 0.59), and MGL (AUC = 0.531, sensitivity = 0.54, and specificity = 0.48). In patients with DED, NIBUT showed a significant correlation with TMH (R = 0.347, P = 0.002) and blinking analysis (R = 0.356, P

The aim of this case report was to evaluate the efficacy of a new platelet-rich plasma preparation and its regenerative capacity of bone periapical tissue for the treatment of a very compromised endodontic treated tooth, with a periapical lesion of 1.5 cm in diameter, using a pure platelet concentrate. This is made without the use of anticoagulant or any type of activator, e.g., bovine thrombin, calcium chloride. For this reason, it has been called “Pure”; it is the B.P.F.C.® Bio-Plasma® with Pure Growth Factors (BioPlasma®) designed and developed by Dr. Raffaello Viganò. The patient has read and signed a written consent form. The study protocol was approved by the Ethics Committee for Human Studies, University of Varese. X-ray at 2 and 6 months and 4 years after endodontic surgery demonstrated the success of the treatment.

The impact of the contrast medium on the radiomic textural features (TF) extracted from the CT scan is unclear. We investigated the modification of TFs of colorectal liver metastases (CLM), peritumoral tissue, and liver parenchyma. One hundred and sixty-two patients with 409 CLMs undergoing resection (2017–2020) into a single institution were considered. We analyzed the following volumes of interest (VOIs): The CLM (Tumor-VOI); a 5-mm parenchyma rim around the CLM (Margin-VOI); and a 2-mL sample of parenchyma distant from CLM (Liver-VOI). Forty-five TFs were extracted from each VOI (LIFEx®®). Contrast enhancement affected most TFs of the Tumor-VOI (71%) and Margin-VOI (62%), and part of those of the Liver-VOI (44%, p = 0.010). After contrast administration, entropy increased and energy decreased in the Tumor-VOI (0.93 ± 0.10 vs. 0.85 ± 0.14 in pre-contrast; 0.14 ± 0.03 vs. 0.18 ± 0.04, p < 0.001) and Margin-VOI (0.89 ± 0.11 vs. 0.85 ± 0.12; 0.16 ± 0.04 vs. 0.18 ± 0.04, p < 0.001), while remaining stable in the Liver-VOI. Comparing the VOIs, pre-contrast Tumor and Margin-VOI had similar entropy and energy (0.85/0.18 for both), while Liver-VOI had lower values (0.76/0.21, p < 0.001). In the portal phase, a gradient was observed (entropy: Tumor > Margin > Liver; energy: Tumor < Margin < Liver, p < 0.001). Contrast enhancement affected TFs of CLM, while it did not modify entropy and energy of parenchyma. TFs of the peritumoral tissue had modifications similar to the Tumor-VOI despite its radiological aspect being equal to non-tumoral parenchyma.

A 33-year-old male patient comes to our observation for a slight discomfort in the left side of the tongue. The patient reported good general health and that he have sometimes taken benzodiazepine in periods of stress. The dental abrasion showed the presence of bruxism. On an objective examination we could notice the simultaneous presence of a "toothed tongue" and a slightly area of erosion on the left side of the dorsal tongue, with an irregular white halo around it. This lesion, appeared from some days, is symptomatic. The diagnosis is compatible for benign migratory glossitis. The patient claimed to have never suffered of skin diseases strongly related to migratory glossitis. It is possible that the bruxism may have determined the presence of that lateral tongue shape and that stress may be the main cause of the appearance of migratory glossitis. The simultaneous presence of the two conditions has never been documented in the scientific literature and we do not exclude that there may be a correlation to the genesis of both lesions. Sometimes the presence of a tongue with this morphology could be the result of a trauma or a surgery. The lingual erosion can be placed in differential diagnosis with a heat burn or a chemical burn.

A 64-year-old patient went to our private practice for a follow-up visit. The medical history reported mild hypertension, she was taking statins to control cholesterol and she reported to be positive for hepatitis B without however having had symptoms and signs of disease. She accidentally discovered through blood tests performed many years ago, to have contracted the HBV infection without realizing it and having overcome it. She has undergone tonsillectomy in adolescence. She had a very poor oral hygiene condition, partial upper and lower removable prostheses, and is a strong smoker (more than 20 cigarettes a day for decades). The patient presented dark pigmentations on the bilateral cheeks. On the soft palate there were pigmented areas, very large, brown in color and the patient, said to have noticed them since young, and that have not undergone evolution. The diagnostic hypothesis was smoke hyperpigmentation and probably the presence of the prosthesis did not allow the manifestation of it in the gingival tissues and in the hard palate. Pigmentations on the palate could be diagnosed with oral nevi, drug pigmentations or oral melanoma. We decided for a closely follow up of the patient, who did not want to be biopsied. We informed her about the possible risks of developing squamous cell carcinoma in heavy smokers.

A 42 years old male patient went to our observation for a white lesion in the left cheek presented 5 months ago. He reported general good health, a previous diagnosis of genital lichen planus. During the clinical examination we observed a white not scrapable lesion of 3 cm in the left cheek and 2 small esophitic lesions in the gingival tissue near the retromolar trigone, with cauliflower shape. The lesions is not linked with a traumatic event and we decided to make an incisional biopsy and 2 excisional biopsies for esophitic lesions on the gingiva, with a temporary diagnosis of leukoplakia and HPV squamous papilloma. The histological examination confirms instead the presence of an oral plaque lichen planus, without signs of dysplasia and the presence of 2 squamous papillomas on the tissue removed in the gingival. It is the first documented case in literature of an oral lichen planus which occurs many years after genital lesions, rare in a male subject. In addition, the simultaneous presence of HPV lesions in the same oral anatomic region is particular. Treatment includes topical therapy with podophyllin for HPV lesions or surgical excision and medical treatment of lichen planus with topical cortisones, immunosuppressants or aloe vera-based gels.

The purpose of the present study was to evaluate changes of signs and symptoms in patients with meibomian gland dysfunction (MGD) treated with intense regulated pulsed light (IRPL), and to further investigate which parameter could predict positive outcomes of the procedure. Twenty-eight patients who bilaterally received three IRPL sessions at day 1, 15, and 45 satisfied the criteria and were included in the study. Non-invasive break-up time (NIBUT), lipid layer thickness (LLT), meibography, tear osmolarity, and ocular discomfort symptoms were measured before and 30 days after the last IRPL session. Qualified or complete success was defined in the presence of an improvement of symptoms associated with an increase of NIBUT (< or ≥ 20%). After IRPL treatment, median NIBUT and LLT increased from 7.5 to 10.2 s and 2.0 to 3.0, respectively (p p = 0.002). Subjective symptoms improved after IRPL in 26 patients. Qualified success was reached in 34 eyes, while complete success in 16 eyes. Patients with lower baseline break-up time (BUT) values showed better response to treatment (p = 0.04). In conclusion, IRPL improved signs and symptoms in MGD patients, while lower baseline NIBUT values were predictive of better response to IRPL.