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The "Urbino Charter" is a document aimed at promoting the wellbeing of the working person that the Olympus Observatory of the University of Urbino Carlo Bo and the Rubes Triva National Foundation, a joint body in the field of environmental hygiene, presented in Bilbao at a public conference in March 2023. The Charter has the objective of stimulating reflection on the issues related to prevention while drawing attention to the essential values for the effective protection of workers' health, safety and well-being. This commentary has the aim of presenting the 10 statements of the Chart, from a perspective of Occupational health and safety. [ABSTRACT FROM AUTHOR]

Introduction: Status Epilepticus (SE) stands as a prominent neurological emergency, showing a mortality rate of approximately 20%. Since February 2021, a worldwide vaccination campaign has been launched against the Coronavirus 19 disease (COVID-19) pandemic. Several possible vaccine-related adverse events have been identified, including neurological manifestations. SE is beginning to surface in literature as an emergent condition in COVID-19-vaccinated individuals, though defined reasons accounting for this correlation are still missing., Methods: We report two cases of SE related to the SARS-CoV-2 vaccine. In addition, we performed a systematic search of the literature to identify the consistency of the association between the SARS-CoV-2 vaccine and the SE onset. The following databases were consulted: PubMed and Google Scholar., Results: Two novel super-refractory status epilepticus (SRSE) cases associated with the BNT162b2 mRNA COVID-19 vaccine were identified. Both patients received the second dose of the vaccine about 14 days prior to SE onset. Patients showed a non-convulsive semiology and were treated with a combined anesthetic and immunomodulant therapy, leading to SE resolution in both cases. The literature review identified seven additional cases, primarily non-convulsive SE. Four patients received the Spikevax (ex-COVID-19 Moderna mRNA -1273 vaccine), 2 patients the BNT162b2 (Pfizer/Biotech), and 1 patient the ChAdOx1-s (AstraZeneca) vaccine. The first vaccine dose (5/7, 71.4%) emerged as the most frequently associated with SE onset, which manifested at an average of 4.5 days (± 3.4) following vaccination. Five patients presented RSE and required continuous intravenous anesthetic drug administration. Resolution of SE was achieved in all cases., Conclusions: Status Epilepticus is a rare complication associated with Sars-CoV-2 vaccines. Additional studies are needed to ascertain the potential association between Sars-CoV-2 vaccines and status epilepticus., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Status Epilepticus (SE) can occur in patients without a previous epilepsy diagnosis, a condition identified as "new-onset status epilepticus" (NOSE). Treatment with benzodiazepine may fail in NOSE termination, requiring anti-seizure medication (ASM) employment. The term "established NOSE" (eNOSE) is generally employed in this context. This study aims to describe the main clinical characteristics of a large sample of patients suffering from eNOSE, compare the ASM efficacy, and explore the risk factors associated with ASM treatment unresponsiveness and eNOSE-associated mortality., Methods: Adult patients diagnosed with eNOSE were retrospectively selected between January 2016 and December 2022. We reviewed demographics, clinical data, diagnostic work-up, and treatment. We considered the last ASM introduced before the eNOSE termination as effective., Results: 123 patients were included (age: 67.9 ± 17.3). eNOSE acute etiology was mostly reported. In the overall cohort, phenytoin showed the highest response rate (p = 0.01). In the pairwise comparisons, valproate was superior to levetiracetam (p = 0.02) but not to lacosamide (p = 0.50). Phenytoin had a significantly higher resolution rate than levetiracetam (p = 0.001) but not lacosamide (p = 0.14). Thirty patients were refractory to ASM treatment. No predictors of refractoriness were identified. Thirty-nine patients died. Age and GCS were identified as eNOSE-related mortality risk factors., Conclusion: eNOSE frequently has an acute etiology with several associated syndromes. Phenytoin is more effective in managing eNOSE, even though lacosamide, valproate, and levetiracetam can represent further therapeutic options. Age and GCS are the main risk factors for eNOSE-associated mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Anti-N-methyl-D-aspartate receptor (NMDAr) antibody encephalitis is an autoimmune disorder characterized by synaptic NMDAr current disruption and receptor hypofunction, often affecting women during pregnancy. Clinical manifestations associated with anti-NMDAr encephalitis can occur both in the mother and fetus., Methods: We generated a systematic search of the literature to identify epidemiological, clinical, and serological data related to pregnant women with anti-NMDAr encephalitis and their children, analyzing the fetal outcomes. We examined the age and neurologic symptoms of the mothers, the presence of an underlying tumor, immunotherapies used during pregnancy, duration of the pregnancy, and type of delivery., Results: Data from 41 patients were extrapolated from the included studies. Spontaneous interruption of pregnancy, premature birth, and cesarean section were reported in pregnant women with NMDAr encephalitis. Several fetal and neonatal symptoms (e.g., movement disorders, spina bifida, poor sucking, respiratory distress, cardiac arrhythmias, infections, icterus, hypoglycemia, and low birth weight) depending on the mother's serum anti-NR1 concentration were also reported., Conclusions: We characterized the outcomes of children born from mothers with anti-NMDAr encephalitis, analyzing the pivotal risk factors related to pregnancy and maternal disorder. Neuropsychiatric involvement seems strictly related to pathogenic NMDAr antibodies detected in maternal and/or neonatal serum. These findings clarify a complex condition to manage, outlining the risks associated with pregnant women with anti-NMDAr encephalitis and also providing a concrete guide for therapeutic strategies to prevent potential harm to the fetus and the child's neurodevelopment., (© 2024. The Author(s).)

Background: The proline-rich transmembrane protein 2 (PRRT2) is a synaptic protein involved in neurotransmitter vesicle release. PRRT2 protein is highly expressed in the cerebellum, cerebral cortex, basal ganglia, and hippocampus. Variants in PRRT2 have been identified as a cause of several neurological disorders, including epilepsy, movement disorders, and headache., Methods: We report two families carrying two distinct PRRT2 mutations showing childhood onset of movement disorders, headache, and epilepsy. Demographics, clinical, EEG, neuroimaging, and genetic sequencing study data were collected. A systematic review of the literature was also performed to dissect the most frequently reported PRRT2-associated epileptic phenotypes., Results: two variants in PRRT2 gene (NM_145239.3:c718C>T, p.Arg240Ter; c.649dupC, p.Arg217Profs*8) were identified. The two variants altered the same extracellular domain of PRRT2. The de novo PRRT2 mutation (c718C>T, p.Arg240Ter) was related to multi-drug-resistant epilepsy. According to the literature, homozygous, biallelic variants and 16p11.2 deletions lead to PRRT2 haploinsufficiency and a more severe phenotype., Conclusions: PRRT2 mutations can be associated with several epileptic phenotypes ranging from benign ASM-responsive form to more severe epileptic encephalopathies. Identifying PRRT2 variants in epilepsy patients may help achieve more personalized treatment approaches. However, phenotype-genotype correlations remain a challenge., Competing Interests: Conflict of interest statement The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

High-grade gliomas (HGGs) constitute the most common malignant primary brain tumor with a poor prognosis despite the standard multimodal therapy. In recent years, immunotherapy has changed the prognosis of many cancers, increasing the hope for HGG therapy. We conducted a comprehensive search on PubMed, Scopus, Embase, and Web of Science databases to include relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Fifty-two papers were finally included (44 phase II and eight phase III clinical trials) and further divided into four different subgroups: 14 peptide vaccine trials, 15 dendritic cell vaccination (DCV) trials, six immune checkpoint inhibitor (ICI) trials, and 17 miscellaneous group trials that included both "active" and "passive" immunotherapies. In the last decade, immunotherapy created great hope to increase the survival of patients affected by HGGs; however, it has yielded mostly dismal results in the setting of phase III clinical trials. An in-depth analysis of these clinical results provides clues about common patterns that have led to failures at the clinical level and helps shape the perspective for the next generation of immunotherapies in neuro-oncology., (© 2024. Fondazione Società Italiana di Neurologia.)

Introduction: The management of cardiopulmonary bypass (CPB) is still challenging in certain circumstances, especially for patients with anatomical variations. This challenge is even harder for reoperations, which are associated with increased morbidity and mortality risk., Case Report: We describe a minimally invasive, beating-heart redo tricuspid valve replacement in a 71-years old woman with persistent left superior vena cava., Discussion: Preoperative planning via CT-scan, teamwork and custom-made management of CPB are crucial for reoperations with anatomical variations. The perfusionist has a pivotal role in constructing and managing the CPB., Conclusion: We describe a strategy achieving the benefits of minimally invasive endoscopic and beating-heart surgery (avoidance of resternotomy risk and associated morbidity, right ventricular protection) in reoperative tricuspid surgery with persistent upper left vena cava., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Epilepsy is one of the most frequent neurological comorbidities in patients with Down Syndrome (DS). Young patients and adults are the most affected, the latter mostly showing a phenotype labeled as "Late-onset myoclonic epilepsy" (LOMEDS). Status epilepticus (SE) is a life-threatening complication in patients with epilepsy. In this study, we described a non-convulsive SE (NCSE) case in a patient diagnosed with LOMEDS. We also performed a systematic review of the literature on SE diagnosis and treatment in patients with Down Syndrome., Methods: Clinical and demographic characteristics of a DS patient diagnosed with NCSE were described. The systematic literature search dissected the diagnostic and therapeutic management of SE in patients with DS. The following databases were used: PubMed, EMBASE, and Google Scholar., Results: 5 DS individuals (4 from the past literature + 1 novel case report) with SE have been identified. The median age at SE onset was 42 years (IQR: 21-60.5 years). The most common SE type was myoclonic SE (MSE), followed by NCSE. Two cases of acute symptomatic etiology were described, whereas a progressive symptomatic etiology was otherwise reported. Ictal EEG recording information was available in two patients who showed generalized spike waves and polyspike and wave discharges. In 3 cases, SE was treated with intravenous antiseizure medications that produced a complete resolution., Conclusion: SE may represent a rare complication in patients with DS. Although no definitive conclusions may be achieved due to the lack of evidence, treatment with valproic acid seems effective, especially in MSE. NCSE management is more challenging. It requires low doses of anesthetics, which should be used cautiously due to the high rate of complications., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Several reports have described the autoimmune encephalitis' (AE) possible onset during pregnancy. In this systematic review, we summarize the available data on the diagnostic and therapeutic approach to AE during pregnancy, highlighting the associated maternal and fetal clinical outcomes. A systematic search of the literature was performed. The following databases were used: PubMed, Google Scholar, EMBASE, and CrossRef. The revision was registered on the PROSPERO platform (CRD42022336357). Forty-nine patients were included. AE onset was mainly observed during the first and the second trimester of pregnancy with psychiatric manifestations and seizures as main onset symptoms. CSF analysis showed AE-specific autoantibody positivity in 33 patients (anti-NMDA receptor as the most frequent). EEG generally showed normal findings. MRI revealed pathological findings in less than half of patients. Tumor screening was positive in 14 cases. First-line immunotherapy (single or combined) was generally employed while second line was administered in a minority of patients. Levetiracetam was the most used antiseizure medication. Cesarean section was performed in 18 women. Most of the women had an excellent early outcome after delivery but 22 showed persistent neurological deficits in long-term follow-up. Fetal outcome was positive in 33 cases, whereas 12 cases of fetal death were reported. A logistic regression showed that no variable significantly influenced the odds of good/bad maternal and fetal clinical outcome. Diagnosis and treatment of AE during pregnancy is challenging. The rate of miscarriage in women with AE seems to be higher than the general population. In addition, mothers may show long-term neurological deficits., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Abstract: The "Urbino Charter" is a document aimed at promoting the well-being of the working person that the Olympus Observatory of the University of Urbino Carlo Bo and the Rubes Triva National Foundation, a joint body in the field of environmental hygiene, presented in Bilbao at a public conference in March 2023. The Charter has the objective of stimulating reflection on the issues related to prevention while drawing attention to the essential values for the effective protection of workers' health, safety and well-being. This commentary has the aim of presenting the 10 statements of the Chart, from a perspective of Occupational health and safety.

Hereditary spastic paraplegia is a neurological condition characterized by predominant axonal degeneration in long spinal tracts, leading to weakness and spasticity in the lower limbs. The nicotinamide adenine dinucleotide (NAD+)-consuming enzyme SARM1 has emerged as a key executioner of axonal degeneration upon nerve transection and in some neuropathies. An increase in the nicotinamide mononucleotide/NAD+ ratio activates SARM1, causing catastrophic NAD+ depletion and axonal degeneration. However, the role of SARM1 in the pathogenesis of hereditary spastic paraplegia has not been investigated. Here, we report an enhanced mouse model for hereditary spastic paraplegia caused by mutations in SPG7. The eSpg7 knockout mouse carries a deletion in both Spg7 and Afg3l1, a redundant homologue expressed in mice but not in humans. The eSpg7 knockout mice recapitulate the phenotypic features of human patients, showing progressive symptoms of spastic-ataxia and degeneration of axons in the spinal cord as well as the cerebellum. We show that the lack of SPG7 rewires the mitochondrial proteome in both tissues, leading to an early onset decrease in mito-ribosomal subunits and a remodelling of mitochondrial solute carriers and transporters. To interrogate mechanisms leading to axonal degeneration in this mouse model, we explored the involvement of SARM1. Deletion of SARM1 delays the appearance of ataxic signs, rescues mitochondrial swelling and axonal degeneration of cerebellar granule cells and dampens neuroinflammation in the cerebellum. The loss of SARM1 also prevents endoplasmic reticulum abnormalities in long spinal cord axons, but does not halt the degeneration of these axons. Our data thus reveal a neuron-specific interplay between SARM1 and mitochondrial dysfunction caused by lack of SPG7 in hereditary spastic paraplegia., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Glioblastoma (GBM) is the most common primary brain tumor in adulthood. Initial diagnosis is generally based on clinical and MRI findings, which may be misinterpreted as other neurological pictures, including autoimmune encephalitis (AE). AE is a heterogeneous group of neuroinflammatory diseases due to the presence of auto-antibodies targeting antigens on neuronal synaptic or cell surface. In the present report, we describe two peculiar cases of GBM initially misdiagnosed as AE, focusing on the diagnostic pitfalls and the treatment strategies., Methods: We report the case of two patients with high-grade brain tumors, initially misdiagnosed and treated for AE. Clinical, laboratory, and neuroradiological data are discussed in terms of differential diagnosis between AE and GBM., Results: The presence of atypical brain MRI findings and the unresponsiveness to immunosuppressive treatment are major red flags in the differential diagnosis between AE and GBM. In these cases, a brain biopsy is necessary to confirm the diagnosis., Conclusions: Atypical brain tumor presentation causes a diagnostic and therapeutic delay. A positive onconeural autoantibodies result should always be interpreted cautiously, considering the possibility of a false-positive test. A brain biopsy is mandatory for a definite diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Consoli, Dono, Evangelista, Corniello, Onofrj, Thomas and Sensi.)

In patients with a prohibitive surgical risk, the AngioVac cannula can be used to remove left-sided cardiac masses, as an off-label adaptation of the device. We herein describe a novel micro-invasive approach to gain access to the left atrium for the aspiration of a mitral valve mass in a patient affected by severe coronavirus disease 2019. Through a right anterior mini-thoracotomy, the right superior pulmonary vein was accessed and used to insert the aspiration cannula. A parallel venous-arterial extracorporeal membrane oxygenation (ECMO)-like circuit provided circulatory and respiratory support to ensure proper intra- and postoperative hemodynamic stabilization., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Introduction: The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS), in people suffering from cognitive decline in Down syndrome (DS). In this review, we analyzed available data on the diagnostic and therapeutic management of individuals with LOMEDS., Methods: We performed a systematic search of the literature to identify the diagnostic and therapeutic management of patients with LOMEDS. The following databases were used: PubMed, Google Scholar, EMBASE, CrossRef. The protocol was registered on PROSPERO (registration code: CRD42023390748)., Results: Data from 46 patients were included. DS was diagnosed according to the patient's clinical and genetic characteristics. Diagnosis of Alzheimer's dementia (AD) preceded the onset of epilepsy in all cases. Both myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were reported, the latter preceding the onset of MS in 28 cases. EEG was performed in 45 patients, showing diffuse theta/delta slowing with superimposed generalized spike-and-wave or polyspike-and-wave. A diffuse cortical atrophy was detected in 34 patients on neuroimaging. Twenty-seven patients were treated with antiseizure medication (ASM) monotherapy, with reduced seizure frequency in 17 patients. Levetiracetam and valproic acid were the most used ASMs. Up to 41% of patients were unresponsive to first-line treatment and needed adjunctive therapy for seizure control., Conclusions: AD-related pathological changes in the brain may play a role in LOMEDS onset, although the mechanism underlying this phenomenon is still unknown. EEG remains the most relevant investigation to be performed. A significant percentage of patients developed a first-line ASM refractory epilepsy. ASMs which modulate the glutamatergic system may represent a good therapeutic option., Competing Interests: Declaration of Competing Interest Authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Sudden unexpected death in epilepsy (SUDEP) is a sudden, unexpected death in people with epilepsy, with or without evidence of an epileptic seizure. The pathophysiological mechanism underlying SUDEP appears to be partly associated with an autonomic nervous system (ANS) dysfunction. Heart rate variability (HRV) analysis is a reliable, non-invasive method for detecting fluctuations in the ANS. In this systematic review we analyzed the data available in the literature on changes in HRV parameters in patients with SUDEP., Methods: We carried out a systematic search of the literature to identify the quantitative variations of HRV in epileptic patients with SUDEP. The following databases were used: Pubmed, Google Scholar, EMBASE, and CrossRef. A pooled analysis was carried out, and the results obtained were compared using mean difference (MD). The review was registered on the PROSPERO platform (CRD42021291586)., Results: Seven articles were included, with a total of 72 SUDEP cases associated with altered HRV parameters. Generally, a reduction of SDNN (standard deviation of the RR intervals) and RMSSD (root mean square differences of successive RR intervals) was reported in most SUDEP patients. According to MD, the SUDEP patients showed no differences in time and frequency domain parameters compared to controls. However, a trend toward increased low frequency and high frequency ratio (LF/HF) was observed in the SUDEP patients., Conclusions: HRV analysis is a valuable method for assessing cardiovascular risk and cardioautonomic impairment. Although a possible association between HRV variation and SUDEP has been reported, further studies are needed to assess the potential role of HRV modifications as a SUDEP biomarker., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

We present the case of a 60-year-old male patient who underwent tetralogy of Fallot repair at 7 years of age and then developed severe degenerative mitral regurgitation during adulthood. Given the increased surgical risk (obesity, obstructive sleep apnea syndrome, and reoperation), the patient underwent a successful microinvasive mitral valve repair with neochordae implantation. ( Level of Difficulty: Advanced. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Objectives: Temporal lobe epilepsy (TLE) is the most frequent form of focal epilepsy. TLE is associated with cardio-autonomic dysfunction and increased cardiovascular (CV) risk in patients over the fifth decade of age. In these subjects, TLE can be classified as early-onset (EOTLE; i.e., patients who had developed epilepsy in their youth) and late-onset (LOTLE; i.e., patients who developed epilepsy in adulthood). Heart rate variability (HRV) analysis is useful for assessing cardio-autonomic function and identifying patients with increased CV risk. This study compared changes in HRV occurring in patients over the age of 50, with EOTLE or LOTLE., Methods: We enrolled twenty-seven adults with LOTLE and 23 with EOTLE. Each patient underwent a EEG and EKG recording during 20-minutes of resting state and a 5-minutes hyperventilation (HV). Short-term HRV analysis was performed both in time and frequency domains. Linear Mixed Models (LMM) were used to analyze HRV parameters according to the condition (baseline and HV) and group (LOTLE and EOTLE groups)., Results: Compared to the LOTLE group, the EOTLE group showed significantly decreased LnRMSSD (natural logarithm of the root mean square of the difference between contiguous RR intervals) (p-value=0.05), LnHF ms 2 (natural logarithm of high frequency absolute power) (p-value=0.05), HF n.u. (high frequency power expressed in normalized units) (p-value=0.008) and HF% (high frequency power expressed in percentage) (p-value=0.01). In addition, EOTLE patients exhibited increased LF n.u. (low frequency power expressed in normalized units) (p-value=0.008) and LF/HF (low frequency/high frequency) ratio (p-value=0.007). During HV, the LOTLE group exhibited a multiplicative effect for the interaction between group and condition with increased LF n.u. (p = 0.003) and LF% (low frequency expressed in percentage) (p = 0.05) values., Conclusions: EOTLE is associated with reduced vagal tone compared to LOTLE. Patients with EOTLE may have a higher risk of developing cardiac dysfunction or cardiac arrhythmia than LOTLE patients., Competing Interests: Declaration of Copmpeting Interest The authors confirm no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

We investigated the efficacy, safety, and versatility of the AngioVac (AngioDynamics, Latham, NY) system for the treatment of intravascular and intracardiac masses of different origins. We prospectively enrolled all consecutive patients treated with the AngioVac system between July-2016 and November-2021 at our institution. Three configurations of the device were adopted in 44 patients: a venous-venous circuit in 21 cases (47.7%), a venous-arterial ECMO-like configuration in 20 (45.5%), and a venous-arterial-arterial circuit with 2 centrifugal pumps for left-sided cardiac masses in 3 (6.8%). Successful removal of the mass was achieved in 41 patients (93.2%), while in the other cases conversion to full sternotomy was necessary. Intraoperative complications occurred in 3 cases (6.8%), including 1 death, 1 pulmonary embolization, and 1 cardiac perforation. The AngioVac system is a valid, safe, and versatile option for the treatment of intravascular masses also in patients with prohibitive surgical risk., Competing Interests: Disclosures None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aim of this study was to compare early clinical and hemodynamic outcomes of Intuity and ME bioprostheses. A propensity score weighting approach was performed. Preoperative variables were defined according to EuroSCORE criteria and postoperative complications according to VARC-2 definitions. We evaluated 375 patients who underwent SAVR with the 2 study devices. Intuity and ME were implanted in 252 (67.2%) and in 123 (32.8%) patients, respectively. There were no differences in terms of postoperative complications, including mortality (1% in each group; OR 0.46[0.05;4.21]). The incidence of pace-maker implantation was 6% and 5% in Intuity and ME groups, respectively (OR 0.53[0.27;1.07]). Intuity showed significantly lower gradients (Median mean gradients: 9mmHg vs 14mmHg, P<0.001), larger effective orifice area index (1.13cm2/m2 vs 1cm2/m2, P=0.007) and lower incidence of patient-prosthesis mismatch (7.1% vs 22.8%, P=0.006). The RD Intuity provides similar early clinical outcomes but shows significantly better hemodynamic performance compared to the ME valve., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures but are not due to underlying epileptic activity and in some cases coexist alongside epilepsy. We described the clinical characteristics of patients with PNES as reported in the literature from the outbreak of the COVID-19 pandemic. We evaluated differences between patients with a diagnosis made immediately before the pandemic (pPNES) and those newly diagnosed during it (nPNES)., Methods: A systematic search with individual patient analysis of PNES cases published since the COVID-19 pandemic outbreak was performed. Differences between pPNES and nPNES were analyzed using Chi-square or Fisher exact test., Results: Eleven articles were included, with 133 patients (106 pPNES and 27 nPNES). In the pPNES group, PNES frequency increased during the pandemic in 20/106 patients, whereas in 78/106, the frequency remained stable or decreased. nPNES was associated with higher risks of SARS-CoV-2 infection and epilepsy diagnosis, whereas psychiatric comorbidities were less frequent., Conclusions: During the pandemic, most patients with pPNES remained stable or improved, whereas nPNES was associated with a lower burden of psychiatric comorbidities. These intriguing findings suggest that, at least in some patients, the COVID-19 pandemic may not necessarily lead to worsening in the frequency of PNES and quality of life., Competing Interests: Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Clinical outcomes of 2 generations of pericardial bioprostheses in concomitant aortic valve and coronary artery bypass graft surgery were analysed., Methods: Patients were recruited from 2 European centres and divided into 2 groups based on the type of aortic bioprosthesis used: Edwards Intuity Elite™ rapid-deployment (RD) bioprostheses or standard Edwards Magna Ease (ME). A propensity score weighting approach was used for data analysis., Results: A total of 285 patients were included: 144 (50.5%) in the RD group and 141 (49.5%) in the ME group. Thirty-day mortality was 2.8% (RD) and 5% (ME) (P = 0.09). Significantly shorter times of aortic cross-clamp and cardiopulmonary bypass were observed in the RD cohort [94 vs 120 min (P &lt; 0.001); 128 vs 160 min (P &lt; 0.001)]. The RD group was associated with a lower median transvalvular gradient at discharge and follow-up (both P &lt; 0.001). However, 5-year survival was not different, being 93% in RD patients and 91% in the ME group [hazard ratio 0.89 (95% confidence interval: 0.38-2.09), P = 0.784]. The 5-year cumulative incidence of combined events (including percutaneous coronary interventions, endocarditis, thromboembolic events, rehospitalizations and bleeding) favoured the ME group [16.1% (RD) vs 7.3% (ME)] [hazard ratio 2.38 (95% confidence interval:1.03-5.52), P = 0.043]. However, this turned similar when the Cox model analysis was adjusted for revascularization variables (P = 0.067)., Conclusions: RD and ME pericardial bioprostheses used in concomitant aortic valve replacement and coronary artery revascularization provide equivalent clinical and haemodynamic 5-year outcomes, despite constant lower transvalvular gradients and shorter surgical operating times observed with RD technology., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Migraine is a common neurological disorder impairing the quality of life of patients. The condition requires, as an acute or prophylactic line of intervention, the frequent use of drugs acting on the central nervous system (CNS). The long-term impact of these medications on cognition and neurodegeneration has never been consistently assessed. The paper reviews pharmacological migraine treatments and discusses their biological and clinical effects on the CNS. The different anti-migraine drugs show distinct profiles concerning neurodegeneration and the risk of cognitive deficits. These features should be carefully evaluated when prescribing a pharmacological treatment as many migraineurs are of scholar or working age and their performances may be affected by drug misuse. Thus, a reconsideration of therapy guidelines is warranted. Furthermore, since conflicting results have emerged in the relationship between migraine and dementia, future studies must consider present and past pharmacological regimens as potential confounding factors.

When approaching infected lead removal in cardiac device-related infective endocarditis (CDRIE), a surgical consideration for large (>20 mm) vegetations is recommended. We report our experience with the removal of large CDRIE vegetations using the AngioVac system, as an alternative to conventional surgery. We retrospectively reviewed all infected lead extractions performed with a prior debulking using the AngioVac system, between October 2016 and April 2022 at our institution. A total of 13 patients presented a mean of 2(1) infected leads after a mean of 5.7(5.7) years from implantation (seven implantable cardioverter-defibrillators, four cardiac resynchronization therapy-defibrillators, and two pacemakers). The AngioVac system was used as a venous−venous bypass in six cases (46.2%), venous−venous ECMO-like circuit (with an oxygenator) in five (38.5%), and venous−arterial ECMO-like circuit in two cases (15.4%). Successful (>70%) aspiration of the vegetations was achieved in 12 patients (92.3%) and an intraoperative complication (cardiac perforation) only occurred in 1 case (7.7%). Subsequent lead extraction was successful in all cases, either manually (38.5%) or using mechanical tools (61.5%). The AngioVac system is a promising effective and safe option for large vegetation debulking in CDRIE. Planning the extracorporeal circuit design may represent the optimal strategy to enhance the tolerability of the procedure and minimize adverse events.

Sars-CoV-2 is a respiratory virus that can access the central nervous system, as indicated by the presence of the virus in patients' cerebrospinal fluid and the occurrence of several neurological syndromes during and after COVID-19. Growing evidence indicates that Sars-CoV-2 can also trigger the acute onset of mood disorders or psychotic symptoms. COVID-19-related first episodes of mania, in subjects with no known history of bipolar disorder, have never been systematically analyzed. Thus, the present study assesses a potential link between the two conditions. This systematic review analyzes cases of first appearance of manic episodes associated with COVID-19. Clinical features, pharmacological therapies, and relationships with pre-existing medical conditions are also appraised. Medical records of twenty-three patients fulfilling the current DSM-5 criteria for manic episode were included. Manic episodes started, on average, after 12.71±6.65 days from the infection onset. Psychotic symptoms were frequently reported. 82.61% of patients exhibited delusions, whereas 39.13% of patients presented hallucinations. A large discrepancy in the diagnostic workups was observed. Mania represents an underestimated clinical presentation of COVID-19. Further studies should focus on the pathophysiological substrates of COVID-19-related mania and pursue appropriate and specific diagnostic and therapeutic workups., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: To investigate the safety and tolerability of COVID-19 vaccines in people with epilepsy (PwE)., Methods: In this multicentric observational cohort study, we recruited adult patients (age > 18 years old) with epilepsy who attended the Outpatient Epilepsy Clinic from 1st July to 30th October 2021. We administered to the patients a structured questionnaire and interview on demographic and epilepsy characteristics, current treatment, previous SARS-CoV-2 infection, vaccine characteristics, post-vaccine seizure relapse, other side effect, variation of sleep habits, caffeine, or alcohol intake. Seizure frequency worsening was defined as a ratio between mean monthly frequency post-vaccination and mean monthly frequency pre-vaccination superior to 1. Patients were categorized in two groups: patients with seizure frequency worsening (WORSE) and patients with seizure stability (STABLE)., Results: A total of 358 people participated with a mean age of 47.46 ± 19.04. Focal seizure (79.1%), generalized epilepsy (20.4%), and unknown types of epilepsy (0.5%) were detected among participants. In total, 31 (8.7%) people expressed that they were not willing to receive a COVID-19 vaccine; 302 patients (92.35%) did not experience an increase in the seizure frequency (STABLE-group) whereas 25 patients (7.65%) had a seizure worsening (WORSE-group). Post-vaccine seizures occurred mainly in the 7 days following the administration of the vaccine. Patients in the WORSE-group were treated with a mean higher number of anti-seizure medication (ASMs) (p = 0.003) and had a higher pre-vaccine seizure frequency (p = 0.009) compared with patients in the STABLE-group. Drug-resistant epilepsy was also associated with seizure worsening (p = 0.01). One-year pre-vaccination seizure frequency pattern demonstrated that patients in the WORSE-group had a higher frequency pattern (p < 0.001). Multivariate analysis of the vaccinated group showed that only the seizure frequency pattern (confidence interval [CI] = 1.257-2.028; p < 0.001) was significantly associated with seizure worsening., Conclusion: In our cohort of vaccinated PwE, only a little percentage had a transient short-term increase of seizure frequency. The present study demonstrates that COVID-19 vaccines have a good safety and tolerability profile in the short term in PwE., (© 2022. The Author(s).)

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice., Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations., Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders., Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

Objective: The temporal lobe plays a central role in the regulation of the "Central Autonomic Network" and cardiovascular functions. The blockade of glutamatergic pathways in the temporal lobe affects cardio-autonomic control. Perampanel (PER) is a non-competitive agonist of the AMPA receptor. This study evaluated PER effects on cardiac autonomic control in patients affected by drug-resistant TLE (DRTLE)., Methods: We enrolled 40 adults with DRTLE treated with PER as add-on therapy (PER group) and 32 DRTLE age, sex, and seizure-frequency matched controls treated with different additional anti-seizure medication (ASM) as add-on therapy (No-PER group). HRV analysis was performed on 5-minute EKG recording in resting state before and 6-months after the introduction of add-on ASM. Linear Mixed Models (LMM) were used to analyzed HRV variables according to time (baseline and 6-months follow-up) and groups., Results: At baseline no differences were detected between PER group and No-PER group according to time-domain and frequency-domain HRV parameters. At the follow-up, in PER group a multiplicative effect for the interaction between treatment and time was observed for MeanRR (ms) (p=0.03), LnRMSSD (ms) (p=0.04), LnHF (ms 2 ) (p<0.001), HF n.u. (p=0.001), HF% (p=0.002) with increased values, and for LnLF (ms 2 ) (p=0.001), LF n.u. (p=0.001), LF% (p=0.01), and LF/HF (p<0.001) with reduced values. The change in seizure frequency after add-on therapy was comparable between the two groups (p=0.81) CONCLUSIONS: Our data support the notion that PER increases the vagal tone in DRTLE. This activity may exert a cardioprotective effect by reducing the risk of developing cardiac arrhythmias. Furthermore, given the correlations between HRV modifications and the occurrence of SUDEP, future studies will need to test the protective effects of PER on SUDEP., (Copyright © 2022. Published by Elsevier Ltd.)

TCC is a semisynthetic molecule widely used in clinical settings as a pain killer and myorelaxant. Several neurological side effects have been reported in association with TCC treatment including somnolence, confusion and seizure, the latter in a lower percentage of patients. Some previous reports described seizure onset after TCC intake in adulthood. However, major epileptological complication, namely status epilepticus, has never been previously reported in association with TCC treatment. In our report, we describe a case of acute refractory non-convulsive status epilepticus (NCSE) in the context of a TCC-induced acute toxic encephalopathy (ATE) in a woman without any previous neurological or physical comorbidities., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: This cross-sectional study aims to evaluate the prevalence and socio-demographic factors associated with workplace bullying, sexual harassment and racial harassment among Italian health workers., Methods: We recruited 3129 participants using an online Italian translation of the 'Workplace Violence in the Health Sector Country Case Studies Research Instruments Survey' (WVHS) questionnaire. Data were analyzed with univariate (chi-square) and multivariate (multiple logistic regression) analysis., Results: Univariate analysis shows that females are significantly more affected by bullying (16.4% vs. 12.3%) and sexual harassment (2.4% vs. 1.3%). On the other hand, males are significantly more affected by racial harassment (3.1% vs. 2.0%). Multivariate analysis shows higher odds of being affected by bullying (OR = 1.30; 95% CI (1.03, 1.64)) and sexual harassment (OR = 2.08; 95% CI (1.04, 4.00)) for females, and higher odds of undergoing racial harassment (OR = 1.55; 95% CI (0.95, 2.53)) for males., Conclusion: This analysis of work situations looks to identify those risk factors, existing or potential, that increase the probability of episodes of violence. A group of work or other subjects identified by direction will have to evaluate the vulnerability of workplaces and establish more effective preventive actions to be adopted.

Background: A 79-year-old woman was admitted to the Neurology Clinic of the University of Chieti-Pescara for a syncope. At admission, the occurrence of an acute stroke was ruled out. Her cognitive status was unimpaired. After three days from the hospitalization, the patient experienced an episode of mixed delirium., Objective: The present case report shows a case of delirium-onset dementia with Lewy bodies (DLB) with a specific electroencephalographic (EEG) pattern from its prodromal stage., Methods: Delirium was assessed by 4AT test. During the hospitalization, the patient underwent a quantitative EEG (QEEG) with spectral analysis. At six months from the episode of delirium, she was tested by neuropsychological evaluation, QEEG, and 18 F-fluorodeoxyglucose PET/CT to assess the onset of a possible cognitive decline., Results: At baseline, the QEEG exam showed a dominant frequency (DF) in the pre-alpha band (7.5 Hz) with a dominant frequency variability (DFV) of 2 Hz. This pattern is typical of DLB at early stage. After six months, she reported attention deficits in association with cognitive fluctuation and REM sleep behavior disorder. The neurological examination revealed signs of parkinsonism. Cognitive status resulted to be impaired (MoCA = 15/30). QEEG recording confirmed the presence of a DLB-typical pattern (DF = 7.5 Hz, DFV = 2.5 Hz). The 18 F-FDG-PET/CT showed a moderate bilateral posterior hypometabolism (occipital and temporal cortex), with relative sparing of the posterior cingulate cortex compared to cuneus/precuneus ( Cingulate Island sign ), and mild bilateral hypometabolism in frontal regions (suggestive of a DLB diagnosis)., Conclusion: EEGs may represent supportive and validated biomarkers for delirium-onset prodromal DLB., Competing Interests: The authors have no conflict of interest to report., (© 2022 – The authors. Published by IOS Press.)