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Background The aims of this study were: to investigate the capacity of the rare disease healthcare network in Campania to diagnose patients with rare diseases during the outbreak of Covid-19; and to shed light on problematic diagnoses during this period. Methods To describe the impact of the Covid-19 pandemic on the diagnosis of patients with rare diseases, a retrospective analysis of the Campania Region Rare Disease Registry was performed. A tailored questionnaire was sent to rare disease experts to investigate major issues during the emergency period. Results Prevalence of new diagnoses of rare disease in March and April 2020 was significantly lower than in 2019 (117 versus 317, P Conclusions This study describes the effects of the Covid-19 outbreak on the diagnosis of rare disease in a single Italian region and investigates potential issues of diagnosis and management during this period.

Hemostasis in neurosurgery is of utmost importance. Bleeding management is one of the crucial steps of each neurosurgical procedure. Several strategies, namely thermal, mechanical, electric, and chemical, have been advocated to face blood loss within the surgical field. Over time, countless hemostatic agents and devices have been proposed. Furthermore, the ever-growing recent technological innovation has made available several novel and interesting tools. Pursuant to their impact on surgical practice, we perceived the imperative to update our previous disclosure paper. Therefore, we reviewed the literature and analyzed technical data sheets of each product in order to provide an updated and comprehensive overview in regard to chemical properties, mechanisms of action, use, complications, tricks, and pitfalls of topical hemostatic agents.

Heart failure (HF) is an important health care issue in children because of its considerable morbidity and mortality. Advanced HF encompasses patients who remained symptomatic despite optimal medical treatment and includes patients who require special management, such as continuous inotropic therapy, mechanical circulatory support, or heart transplantation (HT). HT is the gold standard for children with advanced HF; nonetheless, the number of suitable donors has not increased for decades, leading to prolonged waitlist times and increased mortality rates. Therefore, the role of pediatric mechanic circulatory support has been assessed as an alternative treatment in patients in whom heart transplant could not be performed. The authors discuss the epidemiology, causes, pathophysiology, clinical manifestation, medical treatment, device therapy, and HT in pediatric HF, and a particular emphasis was posed on patients with advanced HF.

BackgroundThere is no consensus on the most effective endovascular technique to use in patients with acute ischemic stroke due to terminal internal carotid artery (ICA) occlusion. The aim of this study was to compare safety and efficacy of the aspiration technique (AT) and combined technique (CT) as first-line approach in terminal ICA occlusions.MethodsWe performed a retrospective analysis of prospectively collected databases from seven Italian stroke centers. Patients were divided into two subgroups according to the first-line approach: AT group or CT group. We followed the STROBE guidelines for cohort studies. We used Chi-square test, one-way and multivariate ANOVA analysis, together with contrast analysis and post hoc tests, logistic regression and Pearson’s bivariate correlation for the statistical analyses.ResultsBetween January 2018 and August 2020, 353 patients were treated for a terminal ICA occlusion, with either AT or CT. CT was associated with a higher Thrombolysis in Cerebral Infarction (TICI) 2B-3 after the first pass (51.0% vs 26.9%) and at the end of the procedure (84% vs 73.3%) and with an improved clinical outcome at discharge (modified Rankin Scale (mRs) 0–2 of 47.8% vs 34.0%) and at 3 months’ follow-up (mRs 0–2 of 56.5% vs 38.9%) compared with AT.ConclusionThrombectomy of terminal ICA occlusions obtained using CT as first-line approach demonstrated better technical and functional outcomes in comparison with AT.

Purpose Tau/MAPT (microtubule associated protein tau) protein is actively studied for the pathologic consequences of its aberrant proteostasis in central nervous system leading to neurodegenerative diseases. Besides its ability to generate insoluble toxic oligomers, Tau homeostasis has attracted attention for its involvement in the formation of the mitotic spindle. This evidence, in association with the description of Tau expression in extra-neuronal tissues, and mainly in cancer tissues, constitutes the rationale for a more in-depth investigation of Tau role also in neoplastic diseases. Methods In our study, we investigated the expression of phosphorylated Tau in prostate cancer cell lines with particular focus on the residue Thr231 present in microtubule binding domain. Results The analysis of prostate cancer cells synchronized with nocodazole demonstrated that the expression of Tau protein phosphorylated at residue Thr231 is restricted to G2/M cell cycle phase. The phosphorylated form was unable to bind tubulin and it does not localize on mitotic spindle. As demonstrated by the use of specific inhibitors, the phosphorylation status of Tau is under the direct control of cdk5 and PP2A, while cdk1 activation was able to exert an indirect control. These mechanisms were also active in cells treated with docetaxel, where counteracting the expression of the dephosphorylated form, by kinase inhibition or protein silencing, determined resistance to drug toxicity. Conclusions We hypothesize that phosphorylation status of Tau is a key marker for G2/M phase in prostate cancer cells and that the forced modulation of Tau phosphorylation can interfere with the capacity of cell to efficiently progress through G2/M phase.

Non-alcoholic fatty liver disease (NAFLD) is considered a relevant liver chronic disease. Variable percentages of NAFLD cases progress from steatosis to steatohepatitis (NASH), cirrhosis and, eventually, hepatocellular carcinoma (HCC). In this study, we aimed to deepen our understanding of expression levels and functional relationships between miR-182-5p and Cyld-Foxo1 in hepatic tissues from C57BL/6J mouse models of diet-induced NAFL/NASH/HCC progression. A miR-182-5p increase was detected early in livers as NAFLD damage progressed, and in tumors compared to peritumor normal tissues. An in vitro assay on HepG2 cells confirmed Cyld and Foxo1, both tumor-suppressor, as miR-182-5p target genes. According to miR-182-5p expression, decreased protein levels were observed in tumors compared to peritumor tissues. Analysis of miR-182-5p, Cyld and Foxo1 expression levels, based on datasets from human HCC samples, showed results consistent with those from our mouse models, and also highlighted the ability of miR-182-5p to distinguish between normal and tumor tissues (AUC 0.83). Overall, this study shows, for the first time, miR-182-5p overexpression and Cyld-Foxo1 downregulation in hepatic tissues and tumors from a diet-induced NAFLD/HCC mouse model. These data were confirmed by the analysis of datasets from human HCC samples, highlighting miR-182-5p diagnostic accuracy and demonstrating the need for further studies to assess its potential role as a biomarker or therapeutic target.

According to the Italian national statistical institute, severe bacterial infections (SBI) in Italy are responsible for 1.7% of mortality under 5 years of age and their recognition is often challenging, especially in the first stages of the disease. We tried to estimate the prevalence of SBI in our target population and to identify signs and symptoms that could guide in the initial evaluation of a child with a possible SBI.We designed a prospective, multicentre study and enrolled patients aged 0-14 years at the first evaluation to the emergency department with an acute illness lasting a maximum of 5 days. The presence of variables suggestive of SBI was collected for every enrolled patient. One week after the enrolment, every patient was followed up by telephone.SBI is more likely to be detected with the 'gut feeling' in both univariate and multivariate models (univariate OR: 7.16, 95% CI: 4.08-12.56; multivariate OR: 5.34, 95% CI: 2.78-10.25), while abnormal breathing pattern resulted significative only in univariate model (OR 3.83, 95% CI: 1.98-7.40). Nevertheless, their associated sensitivity is low.SBI is uncommon in the absence of paediatricians' gut feeling and abnormal respiratory pattern.

Osteogenesis imperfecta (OI) is a rare bone disease due to an abnormal synthesis of 1-type collagen. OI is frequently associated with basilar impression (BI), defined by the elevation of the clivus and floor of the posterior fossa with subsequent migration of the upper cervical spine and the odontoid peg into the base of the skull. Bone intrinsic fragility leading to fractures and deformity, brainstem compression and impaired CSF circulation at cranio-vertebral junction (CVJ) makes the management of these conditions particularly challenging. Different surgical strategies, including posterior fossa decompression with or without instrumentation, transoral or endonasal decompression with posterior occipito-cervical fusion, or halo gravity traction with posterior instrumentation have been reported, but evidence about best modalities treatment is still debated. In this technical note, we present a case of a 16-years-old patient, diagnosed with OI and BI, treated with halo traction, occipito-cervico-thoracic fixation, foramen magnum and upper cervical decompression, and expansive duroplasty. We focus on technical aspects, preoperative work up and postoperative follow up. We also discuss advantages and limitations of this strategy compared to other surgical techniques.

OBJECTIVE Enhanced Recovery After Surgery (ERAS) has led to a paradigm shift in perioperative care through multimodal interventions. Still, ERAS remains a relatively new concept in neurosurgery, and there is no summary of evidence on ERAS applications in cranial neurosurgery. METHODS The authors systematically reviewed the literature using the PubMed/MEDLINE, Embase, Scopus, and Cochrane Library databases for ERAS protocols and elements. Studies had to assess at least one pre-, peri-, or postoperative ERAS element and evaluate at least one of the following outcomes: 1) length of hospital stay, 2) length of ICU stay, 3) postoperative pain, 4) direct and indirect healthcare cost, 5) complication rate, 6) readmission rate, or 7) patient satisfaction. RESULTS A final 27 articles were included in the qualitative analysis, with mixed quality of evidence ranging from high in 3 cases to very low in 1 case. Seventeen studies reported a complete ERAS protocol. Preoperative ERAS elements include patient selection through multidisciplinary team discussion, patient counseling and education to adjust expectations of the postoperative period, and mental state assessment; antimicrobial, steroidal, and antiepileptic prophylaxes; nutritional assessment, as well as preoperative oral carbohydrate loading; and postoperative nausea and vomiting (PONV) prophylaxis. Anesthesiology interventions included local anesthesia for pin sites, regional field block or scalp block, avoidance or minimization of the duration of invasive monitoring, and limitation of intraoperative mannitol. Other intraoperative elements include absorbable skin sutures and avoidance of wound drains. Postoperatively, the authors identified early extubation, observation in a step-down unit instead of routine ICU admission, early mobilization, early fluid de-escalation, early intake of solid food and liquids, early removal of invasive monitoring, professional nutritional assessment, PONV management, nonopioid rescue analgesia, and early postoperative imaging. Other postoperative interventions included discharge criteria standardization and home visits or progress monitoring by a nurse. CONCLUSIONS A wide range of evidence-based interventions are available to improve recovery after elective craniotomy, although there are few published ERAS protocols. Patient-centered optimization of neurosurgical care spanning the pre-, intra-, and postoperative periods is feasible and has already provided positive results in terms of improved outcomes such as postoperative pain, patient satisfaction, reduced length of stay, and cost reduction with an excellent safety profile. Although fast-track recovery protocols and ERAS studies are gaining momentum for elective craniotomy, prospective trials are needed to provide stronger evidence.

Hauer, R, Tessitore, A, Hauer, K, and Tschan, H. Activity profile of international female lacrosse players. J Strength Cond Res 35(11): 3207-3212, 2021-This study was designed to investigate the activity profile in international women's lacrosse match-play. Data were collected of 10 female Austrian lacrosse national team players (29.1 ± 6.1 years; 64.2 ± 5.0 kg; and 165.3 ± 4.1 cm) during 4 games of an international tournament using global positioning system and heart rate monitor devices. The mean average heart rate was 75.3 ± 5.0% of maximum heart rate (HRmax) with 23 ± 6.1% of total playing time spent in HRzone 4 (80-90% of HRmax). The mean distance covered during match-play was 3,791.6 ± 554.5 m, of which 38 ± 6.5% were performed in speed zone 1 (7.0 km·h-1). Ten ±4 sprints per game were conducted with 55 ± 3.8% of accelerations and 59 ± 3.1% of decelerations in zone 1, respectively. Defenders showed greater total distance covered compared with other positions (attack: p = 0.035; d = 0.87; confidence interval [CI] = 0.18-1.56 and midfield: p = 0.006; d = 1.66; CI = 0.93-2.40). Midfielders covered less distance in speed zone 1 (p = 0.032; d = 1.91; CI = 0.53-3.28) compared with attackers, and lower numbers of accelerations (p = 0.042; d = 0.96; CI = 0.20-1.72) and decelerations (p = 0.021; d = 1.79; CI = 0.61-2.97) in zone 3 compared with defenders. Furthermore, attackers showed less distance covered in speed zone 1 (p = 0.09; d = 1.62; CI = 0.86-2.38) compared with defenders. The provided activity data could help coaches and practitioners in designing competition-specific programs for athletes. In addition, positional differences should be taken into account for tactical and physiological aspects.

Introdução: A população idosa vem crescendo consideravelmente no país, com projeções futuras de inversão da pirâmide etária. O aumento da sobrevida se dá pela diminuição de taxas de natalidade e mortalidade infantil e pela melhor qualidade de vida. Esta faz com que os idosos pratiquem atividades que antes não se sentiam capazes, como o sexo. Com a prática frequente, as taxas de infecções sexualmente transmissíveis vêm aumentando consideravelmente, o que coloca a população idosa em situação de vulnerabilidade às infecções. Existem alguns fatores que levam a esse aumento dos índices de infectados. Portanto, o objetivo da presente pesquisa é analisar por meio de dados da última década disponíveis na literatura a justifica deste aumento de infecções sexualmente transmissíveis na população idosa. Metodologia: As pesquisas foram feitas de julho a setembro de 2022 nas bases de dados Scientific Electronic Library Online (SCIELO), Biblioteca Virtual em Saúde (BVS) e Google Acadêmico. Os critérios de elegibilidade são artigos publicados de 2012 até 2022 em português e inglês, e excluídas outras revisões de literatura. Na estratégia de busca, foram identificados 80 trabalhos através dos títulos e excluídos 10 por entrarem nos critérios de exclusão. Na próxima etapa, foram lidos os resumos, sendo selecionados treze trabalhos para leitura completa. Resultados: A amostra compôs treze estudos: dois oriundos da SCIELO, quatro da BVS e sete do Google Acadêmico. Dez artigos avaliaram idosos por meio de questionários/entrevistas, observando dados sociodemográficos e seus conhecimentos e/ou comportamentos perante às infecções sexualmente transmissíveis. Os três artigos restantes também utilizaram questionários e entrevistas, mas com profissionais de saúde, avaliando suas ações relacionadas à temática. Conclusão: Conclui-se, portanto, que os principais fatores que justificam o aumento dos índices de infecções sexualmente transmissíveis são a baixa escolaridade e renda, as crenças, a autopercepção dos idosos e a pouca adesão dos profissionais de saúde em trabalhar com o tema. Logo, sem educação e acesso a informações suficientes, os idosos têm comportamentos sexuais inadequados aumentando as taxas de infecção no Brasil.

Anomalous aortic origin of a coronary artery (AAOCA), especially the interarterial course of the right or left coronary artery, predisposes paediatric patients to myocardial ischaemia. This rare condition is a leading cause of sudden cardiac death. General paediatricians face challenges when diagnosing this anomaly, and they should pay particular attention to the recurrence of exercise-related syncope without prodromal symptoms, chest pain and dyspnoea. An accurate transthoracic echocardiogram with Doppler colour flow mapping is the best method to use to identify AAOCA. CONCLUSION: Identifying an AAOCA is challenging, and we provide advice on clinical red flags and diagnostic approaches for general paediatricians.

According to the latest version of the Diagnostic and Statistical Manual of Mental Disorders, somatic symptom and related disorders (SSRDs) are defined as psychopathological manifestations characterized by physical signs not attributable to organic pathology. Their incidence has grown dramatically over the past few decades, and treatment is challenging. Besides other interventions on the child and the family, physiotherapy is considered an integral part of the treatment, although there is no evidence for its efficacy.The study aimed to review the available proof on the effectiveness of physiotherapy in children and adolescents with SSRDs. A systematic literature search was conducted on MEDLINE/PubMed, CINAHL, Cochrane Library, PsycINFO, and PEDro, including 1999 to 2021. The methodological quality of the publications was assessed by applying the guidelines proposed by the Equator network, according to the different study designs. The scientific bibliography on the subject was minimal and had poor methodological quality. The choice of outcome indicators and the scales to measure them varied from study to study and were not standardized, making comparison and meta-analysis challenging.Conclusion: According to the available evidence, it is impossible to answer the review question regarding the effectiveness of physiotherapy in children and adolescents with SSRDs. It is necessary to improve the methodological quality of the studies. Definition of standard rehabilitation treatments, identification of appropriate result indicators, and adoption of standardized evaluation scales are needed.

Background Clinical trials have demonstrated galcanezumab as safe and effective in migraine prevention. However, real-life data are still lacking and overlook the impact of galcanezumab on those different migraine facets strongly contributing to migraine burden. Herein we report the clinical experience from an Italian real-world setting using galcanezumab in patients with migraine experiencing previous unsuccessful preventive treatments. Methods Forty-three patients with migraine and failure of at least 3 migraine preventive medication classes received monthly galcanezumab 120 mg s.c. At the first administration and after 3 and 6 months, patients underwent extensive interviews to assess clinical parameters of disease severity. Furthermore, validated questionnaires were administered to explore migraine-related disability, impact, and quality of life as well as symptoms of depression or anxiety, pain catastrophizing, sleep quality and the ictal cutaneous allodynia. Results After the third and the sixth administration of monthly galcanezumab 120 mg s.c., headache attacks frequency reduced from 20.56 to 7.44 and 6.37 headache days per month, respectively. Moreover, a significant improvement in headache pain intensity (from 8.95 to 6.84 and 6.21) and duration (from 9.03 to 3.75 and 2.38) as well as in scores assessing migraine related disability and impact, depressive and anxious symptoms, and pain catastrophizing was observed. Furthermore, we demonstrated a significant reduction in the values of “whole pain burden”, a composite score derived from the product of the average of headache frequency, intensity, and duration in the last three months. Conclusion Real-world data support monthly galcanezumab 120 mg s.c. as a safe and effective preventive treatment in reducing headache frequency, intensity, and duration as well as comorbid depressive or anxious symptoms, pain catastrophizing and quality of life in both episodic and chronic migraine patients with previous unsuccessful preventive treatments. Furthermore, we demonstrated that monthly galcanezumab 120 mg s.c. is able to induce a significant improvement in the scores of “whole pain burden”. The latter is a reliable and easy-to-handle tool to be employed in clinical setting to evaluate the effectiveness of preventive drugs (in this case, galcanezumab) or when the decision of continuing the treatment with anti-CGRP mAbs is mandatory.

Introduction The recently released classification has revised the nosology of tremor, defining essential tremor (ET) as a syndrome and fueling an enlightened debate about some newly conceptualized entities such as ET-plus. As a result, precise information of demographics, clinical features, and about the natural history of these conditions are lacking. Methods The ITAlian tremor Network (TITAN) is a multicenter data collection platform, the aim of which is to prospectively assess, according to a standardized protocol, the phenomenology and natural history of tremor syndromes. Results In the first year of activity, 679 patients have been recruited. The frequency of tremor syndromes varied from 32% of ET and 41% of ET-plus to less than 3% of rare forms, including focal tremors (2.30%), task-specific tremors (1.38%), isolated rest tremor (0.61%), and orthostatic tremor (0.61%). Patients with ET-plus were older and had a higher age at onset than ET, but a shorter disease duration, which might suggest that ET-plus is not a disease stage of ET. Familial aggregation of tremor and movement disorders was present in up to 60% of ET cases and in about 40% of patients with tremor combined with dystonia. The body site of tremor onset was different between tremor syndromes, with head tremor being most commonly, but not uniquely, associated with dystonia. Conclusions The TITAN study is anticipated to provide clinically relevant prospective information about the clinical correlates of different tremor syndromes and their specific outcomes and might serve as a basis for future etiological, pathophysiological, and therapeutic research.

Introduction Parkinson’s disease (PD) patients in chronic levodopa treatment may experience motor and non-motor fluctuations, which may affect their quality of life. Safinamide is a new monoamine oxidase B inhibitor, also exerting a non-dopaminergic effect, recently approved as add-on therapy in fluctuating PD patients. Methods We performed a longitudinal prospective study in a cohort of 20 fluctuating PD patients, to test whether safinamide 50 mg may improve non-motor, cognitive, and behavioral symptoms over a 6-month treatment period. At each timepoint, clinical features were assessed by means of validated PD-specific scales. Neuropsychological assessment was performed by exploring all five cognitive domains. Results Compared to baseline, significant improvement was found in PD patients at 6-month follow-up in items investigating interest (p = 0.02), motivation (p = 0.02), and urinary disturbances (p = 0.03). Moreover, neuropsychiatric assessment showed a significant decrease in fatigue and apathy scores (p = 0.02 and p = 0.01, respectively). Motor assessment revealed a significant reduction in the total wake-up time spent in OFF state (p = 0.01). Follow-up neuropsychological evaluation did not reveal any change compared to baseline. Conclusions Our data reveal that, along with motor fluctuation improvement, treatment with safinamide 50 mg may significantly decrease non-motor symptom burden in PD patients. Interestingly, non-dopaminergic mechanisms, such as glutamatergic overdrive, have been demonstrated to play a role in many pathways underlying these symptoms. Thus, we hypothesize that the neurotransmitter receptor-binding profile of safinamide may explain our findings.

Background We described the results of surgical treatment of empyema, tracing outcomes throughout the passage from the open thoracotomy (OT) approach to video-assisted thoracoscopic surgery (VATS) in a single institute. Methods We retrospectively analyzed the records of 88 consecutive patients treated for Stage 2 and 3 empyema (2010-2019). We divided the study period into three groups: OT period (2010-2013), early VATS (2014-2017, from the introduction of VATS program, until acme of learning curve), and late VATS (2018-2019). Groups were compared to investigate the outcomes evolution. Results Most relevant findings of the study were significant variation in postoperative length of stay (median [interquartile range]: 9 days [7.5-10], 10 [7.5-17.5], and 7 [5-10] for OT period, early VATS, and late VATS, respectively, p = 0.005), hospital admission referral to thoracic surgery interval (7.5 days [4.5-11], 6.5 [3-9], and 2.5 [1.5-5.5], p = 0.003), chest tube duration (5.5 days [5-7.5], 6 [4-6], 4 [3-5], p = 0.003), and proportion of operation performed by residents (3 [15%], 6 [16.7%], 14 [43.6%], p = 0.01). Conclusions Our findings pictured the trajectory evolution of outcomes during introduction and consolidation of VATS treatment of empyema. During the early phase, we observed a decline in some indicators that improved significantly in the late VATS period. After a learning curve, all outcomes showed better results and we entered into a teaching phase.

IntroductionDegenerative cervical myelopathy (DCM) is the most common cause of spinal cord impairment. Unfortunately, the condition remains poorly recognised and underdiagnosed. To better identify patients, screening tests that target individuals at high risk would be helpful. One group in particular known to have a high prevalence of DCM consists of patients with lumbar degenerative disease (LDD), with the combined presentation referred to as tandem stenosis. Given that LDD is one of the most common presentations in neurosurgical practice and primary care, it is the objective of the proposed study to administer a screening test to these patients as well as those with risk factors or symptoms which raise the suspicion of underlying DCM.Methods and analysisA screening test based on clinical signs/symptoms and known risk factors of DCM was designed. Screening will be performed in neurosurgical consultations for patients with LDD or those with any suspicion of myelopathy. Points are attributed based on the presence of signs/symptoms of DCM (eg, Hoffmann sign, hyper-reflexia) and for comorbidities that predispose or are frequently associated with cervical myelopathy (eg, rheumatoid arthritis, carpal tunnel syndrome). Patients with ≥3 points undergo cervical MRI examination. Patients with positive MRIs will be consulted and receive assessment via modified Japanese Orthopedic Association and Neck Disability Index scores, and subsequent clinical management will be based on practice guidelines. An exploratory multivariate analysis of the effectiveness and efficiency of this proposed screening test will be evaluated after positively screening 50 patients for DCM.Ethics and disseminationThis study has received research ethics approval from the Swiss Association of Research Ethics Committees (ID: 2020-02785). The results of this study will be disseminated in a journal targeting physicians commonly encountering patients with LDD.

The increasing number of asylum seekers and refugees in Europe calls for even more professionals to take care of refugees' mental health. Although different studies claim that migration could be a potential risk factor for self-harming behaviours, an in-depth exploration of the presence and characteristics of self-harm in the context of asylum is needed. In accordance with PRISMA guidelines, a systematic review was conducted across the databases Scopus, PubMed, Web of Knowledge and PsycArticles, regarding the main features of self-harming behaviour among refugees in Europe. Twelve articles and 3 main trajectories were identified: (1) A context at-risk: self-harm and detention centres; (2) A target at-risk: self-harm and unaccompanied minors; (3) A comparison between the mental health of asylum seekers and natives. Research on this topic in Europe is still underdeveloped and disorganised. Studies have mainly carried out wider quantitative investigations on mental health, usually overlapping self-harm with suicide. Detention centres emerged as the most widely investigated context and the one with the highest risk for self-harming behaviours. Instead, unaccompanied minors emerged as a particularly vulnerable category. Research in this field should be improved, combining quantitative and qualitative methods for a deeper understanding of the meanings of self-harm across cultures.

Neurocutaneous melanosis (NCM) is a rare phakomatosis that may be associated with intracerebral masses. The differential diagnosis of intracerebral masses in NCM is often challenging and should include pigmented and nonpigmented lesions.

Objectives: The cervicothoracic junction (CTJ) is a region of the spine submitted to significant mechanical stress. The peculiar anatomical and biomechanical characteristics make posterior surgical stabilization of this area particularly challenging. We present and discuss our surgical series highlighting the specific surgical challenges provided by this region of the spine.Methods: We have analyzed and reported retrospective data from patients who underwent a posterior cervicothoracic instrumentation between 2011 and 2019 at the Neurosurgical Department of the Geneva University Hospitals. We have discussed C7 and Th1 instrumentation techniques, rods design, extension of constructs and spinal navigation.Results: 36 patients were enrolled. We have preferentially used lateral mass (LM) screws in the subaxial spine, pedicle screws (PS) in C7, Th1 and upper thoracic spine. We have found no superiority of 3D navigation techniques over 2D fluoroscopy guidance in PS placement accuracy, probably due to the relatively small case series. Surgical site infection was the most frequent complication, significantly associated with tumor as diagnosis.Conclusions: When technically feasible, PS represent the technique of choice for C7 and Th1 instrumentation although other safe techniques are available. Different rods constructs are described although significant differences in biomechanical stability still need to be clarified. Spinal navigation should be used whenever available even though 2D fluoroscopy is still a safe option. Posterior instrumentation of the CTJ is a challenging procedure but with correct surgical planning and technique it is safe and effective.

Background In the past decades a plethora of studies has been conducted to explore resting-state functional connectivity (RS-FC) of the brain networks in migraine with conflicting results probably due to the variability and susceptibility of signal fluctuations across the course of RS-FC scan. On the other hand, the structural substrates enabling the functional communications among the brain connectome, characterized by higher stability and reproducibility, have not been widely investigated in migraine by means of graph analysis approach. We hypothesize a rearrangement of the brain connectome with an increase of both strength and density of connections between cortical areas specifically involved in pain perception, processing and modulation in migraine patients. Moreover, such connectome rearrangement, inducing an imbalance between the competing parameters of network efficiency and segregation, may underpin a mismatch between energy resources and demand representing the neuronal correlate of the energetically dysfunctional migraine brain. Methods We investigated, using diffusion-weighted MRI imaging tractography-based graph analysis, the graph-topological indices of the brain “connectome”, a set of grey matter regions (nodes) structurally connected by white matter paths (edges) in 94 patients with migraine without aura compared to 91 healthy controls. Results We observed in migraine patients compared to healthy controls: i) higher local and global network efficiency (p p p Conclusion The imbalance between the need of investing resources to promote network efficiency and the need of minimizing the metabolic cost of wiring probably represents the mechanism underlying migraine patients’ susceptibility to triggers. Such changes in connectome topography suggest an intriguing pathophysiological model of migraine as brain “connectopathy”.

Purpose: The objective of this study is to observe the efficacy of orofacial myofunctional therapy in children who breathe through their mouths “mouth breathers” using a clinical assessment and surface electromyography. Method: 30 nasal breath (control group) and 30 mouth breathers (study group) were evaluated initially, and the study group was re-evaluated after 12 sessions of orofacial myofunctional therapy. Assessments involved the MBGR protocol and surface electromyography. Results: The control group had significantly better scores on all nasal breathing tests compared to mouth breathers both before and after therapy. However, mouth breathers demonstrated statistically significant improvements over time with therapy. Conclusion: After twelve orofacial myology therapy sessions, the mouth breathers improved but not to normal levels. Inadequate muscular strength remained for the required tasks suggesting that additional therapeutic intervention is needed or that therapeutic success is inhibited by a vertical craniofacial growth pattern.

Stem cells offer the basis for the promotion of robust new therapeutic approaches for a variety of human disorders. There are still many limitations to be overcome before clinical therapeutic application, including a better understanding of the mechanism by which stem cell therapies may lead to enhanced recovery. In vitro investigations are necessary to dissect the mechanisms involved and to support the potential development in stem cell‐based therapies. In spite of growing interest in human amniotic fluid stem cells, not much is known about the characteristics of their secretome and regarding the potential neuroprotective mechanism in different pathologies, including stroke. To get more insight on amniotic fluid cells therapeutic potential, signal transduction pathways activated by human amniotic fluid stem cells (hAFSCs)‐derived secretome in a stroke in vitro model (ischemia/reperfusion [I/R] model) were investigated by Western blot. Moreover, miRNA expression in the exosomal fraction of the conditioned medium was analyzed. hAFSCs‐derived secretome was able to activate pro‐survival and anti‐apoptotic pathways. MicroRNA analysis in the exosomal component revealed a panel of 16 overexpressed miRNAs involved in the regulation of coherent signaling pathways. In particular, the pathways of relevance in ischemia/reperfusion, such as neurotrophin signaling, and those related to neuroprotection and neuronal cell death, were analyzed. The results obtained strongly point toward the neuroprotective effects of the hAFSCs‐conditioned medium in the in vitro stroke model here analyzed. This can be achieved by the modulation and activation of pro‐survival processes, at least in part, due to the activity of secreted miRNAs., Neuroprotective effects of human amniotic fluid stem cell‐secretome in an ischemia/reperfusion model.

Sansone, P, Tschan, H, Foster, C, and Tessitore, A. Monitoring training load and perceived recovery in female basketball: Implications for training design. J Strength Cond Res 34(10): 2929-2936, 2020-This study investigated the relationship between internal training load and perceived recovery of semi-professional female basketball players during the competitive season. Eleven female players were monitored for 14 weeks during the in-season phase. For each event (training and game), data were collected as follows: (a) Total Quality Recovery (TQR) score before the event (TQRpre); (b) session Rating of Perceived Exertion (sRPE) 20 minutes after completion of the event, to calculate training load (s-TL) of the event; and (c) TQR scores 12 (TQRpost12) and 24 hours (TQRpost24) after the event. Data were analyzed for daily, weekly, and mesocycle (regular season; regional play-off; and national play-off) time frames. Daily analysis showed that: TQRpost12 was lower than TQRpre (p < 0.001) and TQRpost24 (p < 0.001); s-TL had a moderate negative correlation with TQRpost12 (r = -0.48, p = 0.002); the difference between TQRpre and RPE (TS-Δ) had a very large positive correlation with TQRpost12 (r = 0.70, p < 0.001); and TQRpost24 was not significantly correlated with training parameters. Weekly analysis highlighted a very large negative correlation between the acute:chronic workload ratio and TQR collected at the start of the following week (TQRfw) (r = -0.86, p < 0.001). Finally, although weekly TL and TQRfw did not differ between mesocycles, their correlation increased in the later seasonal phases. This study demonstrated negative relationships between training load and recovery of semi-professional female basketball players at daily, weekly, and mesocycle levels. Therefore, concurrently monitoring training and recovery with the sRPE method and TQR scale is recommended for designing training schedules in basketball.

Eagle Syndrome (ES) is an often misdiagnosed syndrome due to its wide spectrum of signs and symptoms. Recent works have pointed out the relation between ES and some types of craniofacial pain often misdiagnosed with migraine or temporomandibular disorders. Moreover, the presence of Vascular ES as a cause of Carotid Artery Dissection in same cases of stroke as well as cause of intracranial venous hypertension resulting in migraine and other pains has been recently discussed. A multidisciplinary approach is mandatory to allow clinicians to better understand the pathophysiology and clinical main patterns of ES. The aim of the work is to perform a comprehensive review all the clinical patterns and available diagnostic tools to guide clinicians through lights and shadows of such an underestimated syndrome. Finally, a novel flow-chart for comprehensive diagnosis of ES is proposed, including “dynamic” imaging investigating the relationship between stiloyd processes and the neurovascular structures of the neck during head movements.

The management of tandem extracranial internal carotid artery and intracranial large vessel occlusion during endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) has been under-investigated. We sought to investigate outcomes of AIS patients with tandem occlusion (TO) treated with carotid artery stenting (CAS) compared to those not treated with CAS (no-CAS) during EVT.We performed a cohort study using data from AIS patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. Outcomes were 3 months' mortality, functional outcome, complete and successful recanalization, any intracranial hemorrhage, parenchymal hematoma and symptomatic intracerebral hemorrhage.Among 466 AIS patients with TO, CAS patients were 122 and no-CAS patients were 226 (118 excluded). After adjustment for unbalanced variables, CAS was associated with a lower rate of 3 months' mortality (OR 0.407, 95% CI 0.171-0.969, p = 0.042). After adjustment for pre-defined variables, CAS was associated with a lower rate of 3 months' mortality (aOR 0.430, 95% CI 0.187-0.989, p = 0.047) and a higher rate of complete recanalization (aOR 1.986, 95% CI 1.121-3.518, p = 0.019), successful recanalization (aOR 2.433, 95% CI 1.263-4.686, p = 0.008) and parenchymal hematoma (aOR 2.876, 95% CI 1.173-7.050, p = 0.021). CAS was associated with lower 3 months mortality (OR 0.373, 95% CI 0.141-0.982, p = 0.046) and higher rates of successful recanalization (OR 2.082, 95% CI 1.099-3.942, p = 0.024) after adjustment for variables associated with 3 months' mortality and successful recanalization, respectively.Among AIS patients with TO, CAS during EVT was associated with a higher rate of successful reperfusion and a lower rate of 3 months' mortality.

Background Frequency of Advanced Parkinson’s Disease (APD) and its clinical characteristics are still not well defined. Here, we aimed to assess APD prevalence in the Italian OBSERVE-PD cohort, as well as treatment eligibility to device-aided therapies (DAT), and to compare the APD clinical judgment with the established Delphi criteria. Methods This sub-group analysis of the OBSERVE-PD study was performed on patients enrolled by 9 Movement Disorders centers in Italy. Motor and non-motor symptoms, PD characteristics, activities of daily living, and quality of life were assessed. Patient eligibility for DAT, response to current PD treatments, referral process, and the concordance between APD physician’s judgment and Delphi criteria were also assessed. Results According to physician’s judgment, 60 out of 140 patients (43%) had APD. The correlation between physician’s judgment and the overall APD Delphi criteria was substantial (K = 0.743; 95%CI 0.633–0.853), mainly driven by a discrete concordance found for the presence of ≥ 2 h of daily OFF time, presence of troublesome dyskinesia, ≥ 5 times daily oral levodopa dosing, and activities of daily living limitation. Forty-four (73%) APD patients were considered eligible to DAT but only 18 of them (41%) used these therapies, while most patients, independently from their eligibility, continued to use 3–5 oral daily medications, due to fear of invasive solutions and need to have a longer time to decide. Conclusion APD was frequent in the Italian OBSERVE-PD population. DAT in the eligible APD population proved to be underused, in spite of unsatisfactory symptoms control with oral medications in 67% of patients.

ObjectivesThe aim of this study was to determine the prevalence and forms of gender discrimination and sexual harassment experienced by medical students and physicians in French-speaking part of Switzerland.Design and settingWe conducted an online survey using a questionnaire of 9 multiple-choice and 2 open questions between 24 January 2019 and 24 February 2019. Our target population was medical students and physicians working at hospitals and general practitioners from the French-speaking part of Switzerland. The online survey was sent via social media platforms and direct emails. We compared answers between male-determined and female-determined respondents using either χ2 or Fisher’s exact tests.ResultsAmong 1071 responders, a total of 893 were included (625 females, 264 males, 4 non-binary and 1 non-binary and male). 178 were excluded because they did not mention their working place or were working only outside Switzerland. Because of the small number of non-binary participants, they were not contemplated in further statistical analysis. Of 889 participants left, 199 (31.8%) women and 18 (6.8%) men reported having personally experienced gender discrimination, in terms of sexism, difficulties in career development and psychological pressure. Among women, senior attendings were the most affected (55.2%), followed by residents (44.1%) and junior attendings (41.1%). Sexual harassment was equally observed among women (19.0%) and men (16.7%). Compared with men (47.0%), women (61.4%) expressed the need to promote equality and inclusivity in medicine more frequently (pConclusionsGender discrimination in medicine in French-speaking Switzerland affects one-third of women, in particular, those working in hospital settings and senior positions.

Background Despite the growing body of advanced studies investigating the neuronal correlates of pain processing in patients with migraine without aura (MwoA), only few similar studies have been conducted in patients with migraine with aura (MwA). Therefore, we aimed to explore the functional brain response to trigeminal noxious heat stimulation in patients with MwA. Methods Seventeen patients with MwA and 15 age- and sex-matched healthy controls (HC) underwent whole-brain blood oxygen level–dependent (BOLD) fMRI during trigeminal noxious heat stimulation. To examine the specificity of any observed differences between patients with MwA and HC, the functional response of neural pathways to trigeminal noxious heat stimulation in patients with MwA was compared with 18 patients with MwoA. Secondary analyses investigated the correlations between BOLD signal changes and clinical parameters of migraine severity. Results We observed a robust cortical and subcortical pattern of BOLD response to trigeminal noxious heat stimulation across all participants. Patients with MwA showed a significantly increased activity in higher cortical areas known to be part of a distributed network involved in advanced visual processing, including lingual gyrus, inferior parietal lobule, inferior frontal gyrus and medial frontal gyrus. Moreover, a significantly greater cerebellar activation was observed in patients with MwA when compared with both patients with MwA and HC. Interestingly, no correlations were found between migraine severity parameters and magnitude of BOLD response in patients with MwA. Conclusion Our findings, characterized by abnormal visual pathway response to trigeminal noxious heat stimulation, support the role of a functional integration between visual and trigeminal pain networks in the pathophysiological mechanisms underlying migraine with aura. Moreover, they expand the concept of “neurolimbic-pain network” as a model of MwoA including both limbic dysfunction and cortical dys-excitability. Indeed, we suggest a model of “neurolimbic-visual-pain network” in MwA patients, characterized by dysfunctional correlations between pain-modulating circuits not only with the cortical limbic areas but with advanced visual areas as well. Furthermore, the abnormal cerebellar response to trigeminal noxious heat stimulation may suggest a dysfunctional cerebellar inhibitory control on thalamic sensory gating, impinging on the advanced visual processing cortical areas in patients with MwA. Electronic supplementary material The online version of this article (10.1186/s10194-019-1002-3) contains supplementary material, which is available to authorized users.

Background: The presence of patent foramen ovale (PFO) alone does not increase the risk of ischemic stroke. Several prospective studies with a small number of patients have shown that the risk of ischemic stroke is higher in patients with PFO and pulmonary embolism (PE). We studied the association of ischemic stroke in the patients who had PFO with PE (PFOwiPE) and compared with the patients who had PFO without PE (PFOwoPE). Methods: Electronic medical records of 154 adult patients in our internal medicine office were reviewed. Thirty-four patients had PFOwiPE and 120 had PFOwoPE. Independent t -test and Mann-Whitney U-test were used to compare the continuous variables between the two groups, while Chi-square tests were applied to compare the categorical variables between the two groups. Logistic regression was used for multivariate analysis. The dependent variable was stroke and the independent variable of interest was PFO with, or without PE. Results: Mean age of patients with PFOwiPE was 54.8 years and patients with PFOwoPE was 57.8 years (P = 0.331). Mean body mass index (BMI) of the patients with PFOwiPE was significantly greater than the patients with PFOwoPE (32.5 ± 8.84 kg/m 2 vs. 28.4 ± 6.99 kg/m 2 ; P < 0.05). Mean left ventricular ejection fraction (LVEF) and red blood cell (RBC) count of patients with PFOwiPE was significantly lower than patients with PFOwoPE (LVEF 54.9 ± 13.01% vs. 59.6 ± 6.85%, P < 0.05; RBC 4.1 ± 1.203 × 10 6 /µL vs. 4.5 ± 0.596 × 10 6 /µL, P < 0.05). There was significantly higher association of congestive heart failure (CHF) in patients with PFOwiPE compared to patients with PFOwoPE (20.6% vs. 7.5%; P < 0.05). Association of ischemic stroke was 35.3% in patients with PFOwiPE and 39.2% in patients with PFOwoPE. The difference was not statistically significant (P = 0.682). Conclusions: Association of ischemic stroke was similar in patients with PFOwiPE and patients with PFOwoPE. Association of significantly higher BMI, lower LVEF, lower RBC count, and higher frequency of CHF were associated with patients with PFOwiPE compared to the patients with PFOwoPE. J Clin Med Res. 2020;12(3):190-199 doi: https://doi.org/10.14740/jocmr4094

Background Since the pioneering reports of the so-called leonine face in cluster headache (CH) patients, cranial and facial features of these patients have been poorly investigated with conflicting results. We aimed to investigate whether abnormalities in craniometric measurements could characterize male CH patients and represent reliable and reproducible diagnostic biomarkers able to identify CH patients. Methods Brain CT images were recorded between 2018 and 2020 in 24 male patients with CH and in 24 matched healthy controls (HC). Then, craniometric measurements were obtained, and logistic regression and receiver operating characteristic curves analyses were used to identify the craniometric abnormalities able to distinguish CH patients from HC. Results Logistic regression analyses showed that frontal bone height and facial width were able to discriminate, one independently from the other, CH patients from HC with an overall accuracy of 77%. The optimal cutoff score in detecting the probable presence of CH was 11.50 cm for frontal bone height and 13.30 cm for facial width. Discussion In the present study we found, for the first time by means of brain 3D computed tomography approach, abnormal craniometric measurements in CH patients when compared with HC. The absence of differences in smoke and alcohol intake suggests that the observed craniometric abnormalities may represent a specific feature of CH patients. Conclusion The craniometric evaluation by means of brain 3D computed tomography could represent a widespread, noninvasive, and accurate tool to support CH diagnosis to avoid frequent misdiagnosis or delay in the diagnostic process.

Postingestive signals are important for shaping appetitive and consummatory responses, but the brain mechanisms required to assimilate interoceptive events with those at the frontlines of ingestion (taste-guided) are poorly understood. Here, we investigated whether an insular cortex (IC) region, which receives viscerosensory input, including gustatory, is required to modify taste-elicited consummatory reactions in response to a real-time interoceptive change using a serial taste reactivity (TR) test where the rats’ oromotor and somatic reactions to intraoral (IO) infusions of sucrose were periodically assessed over 45 min following lithium chloride (LiCl) administration. Results showed that neurally-intact rats shifted from an ingestive repertoire to an aversive one as LiCl took effect. Overall, this hedonic shift was delayed in rats with bilateral neurotoxic IC lesions. Rats with greater neuronal loss in posterior gustatory IC displayed fewer aversive reactions to sucrose following this initial LiCl injection. We further assessed whether the failure to integrate interoceptive feedback with ongoing taste-guided behavior impaired acquisition and/or expression of conditioned aversion and/or avoidance in these same rats. Although, as a group, LiCl-injected rats with IC lesions subsequently avoided the sugar in a 48-h two-bottle test, their preference for sucrose was significantly greater than that of the LiCl-injected neurally-intact rats. Overall lesion size, as well as proportion of the posterior gustatory and/or anterior visceral IC were each associated with impaired avoidance. These findings reveal new roles for the posterior gustatory and anterior visceral ICs in multisensory integrative function.

Sacral chordoma is a rare primary bone neoplasm associated with high morbidity. The aim of this study is to identify demographic and clinicopathological characteristics of this tumor and evaluate their impact on survival outcomes.The Surveillance, Epidemiology and End Results (SEER) database collecting data between 2000 and 2018 was searched for all cases of sacral chordoma. We analyzed demographic aspects, cancer stage and treatment patterns. Overall survival was calculated using the Kaplan-Meier method and compared between subgroups using the log-rank test. A multivariate Cox hazard regression analysis was conducted to identify independent predictors of overall survival.Four hundred and forty-two patients were identified with a mean age of 62.7 years. Most tumors presented regional invasion at diagnosis (43.2%). Mean overall survival was 124.7 months. No significant difference in terms of overall survival was found between surgery alone and surgery associated with radiotherapy. Both options provided a significantly increased survival than radiotherapy alone. Age of less than 50 years or between 50 and 69 correlated significantly with improved survival.Age and stage at diagnosis impact significantly survival outcomes. Surgery remains the mainstay treatment with the highest overall survival. Its association with radiotherapy is currently questionable and needs further research.

Background: Frontotemporal lobar degeneration (FTLD) designates a group of neurodegenerative diseases with remarkable clinical, pathological, and genetic heterogeneity. Mutations in progranulin gene (GRN) are among the most common causes of familial FTLD. The GRN C157KfsX97 mutation is the most frequent mutation occurring in Southern Italy and has been already described in a previous work. Objective: In this study, we reported on additional cases carrying the same mutation and performed a genetic study on the whole cohort, aiming at demonstrating the existence of a founder effect and estimating the age of this mutation. Methods/Results: Based on the haplotype sharing analysis, a founder effect was highly probable, while the age of the mutation, estimated by means of DMLE+ software, resulted in a range between 52 and 82 generations, with the highest frequency at about 62 generations, 1,550 years ago. Conclusion: This is the first study that reports the age estimation of the most recent common ancestor for the GRN C157KfsX97 mutation recurring in Southern Italy. Mutation dating in a geographically restricted population may be useful in order to plan genetic counseling and screening programs in the field of public health.

Background: Lipoprotein(a) [Lp(a)] is an LDL-like molecule that is likely causal for cardiovascular events and Lp(a) variability has been shown to be mostly of genetic origin. Exogenous hormones (hormone replacement therapy) seem to influence Lp(a) levels, but the impact of endogenous hormone levels on Lp(a) is still unknown. The aim of the study was to assess the effect of endogenous steroid hormone metabolites on Lp(a). Methods: Lipoprotein(a) levels were measured in 1,021 participants from the Swiss Kidney Project on Genes in Hypertension, a family-based, multicentre, population-based prospective cohort study. Endogenous levels of 28 steroid hormone precursors were measured in 24-h urine collections from 883 individuals. Of the participants with Lp(a) data, 1,011 participants had also genotypes available. Results: The participants had an average age of 51 years and 53% were female. Median Lp(a) levels were 62 mg/L, and the 90thpercentile was 616 mg/L. The prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. Forty-three per cent of Lp(a) variability was explained respectively by: age (2%, p-16). Of the 28 endogenous steroid hormones assessed, androstenetriol, androsterone, 16α-OH-DHEA and estriol were nominatively associated with serum Lp(a) levels in univariable analyses and explained 0.4%-1% of Lp(a) variability, but none of them reached significance in multivariable models. Conclusions: In this contemporary population-based study, the prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. The effect of endogenous steroid hormone levels of Lp(a) variability was small at best, suggesting a negligible impact on the wide range of Lp(a) variability.

Background: Progressive supranuclear palsy (PSP) is a rare rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. The use of health-related quality of life (HR-QoL) measures allows assessing changes in health status induced by therapeutic interventions or disease progress in neurodegenerative diseases. The PSP-QoL is a 45-item, self-administered questionnaire designed to evaluate HR-QoL in PSP. Methods and Results: Here, the PSP-QoL was translated into Italian and validated in 190 PSP (96 women and 94 men; mean age ± standard deviation, 72 ± 6.5; mean disease duration, 4.2 ± 2.3) patients diagnosed according to the Movement Disorder Society criteria and recruited in 16 third level movement disorders centers participating in the Neurecanet project. The mean PSP-QoL total score was 77.8 ± 37 (physical subscore, 46.5 ± 18.7; mental subscore, 33.6 ± 19.2). The internal consistency was high (Cronbach’s alpha = 0.954); corrected item-total correlation was > 0.40 for the majority of items. The significant and moderate correlation of the PSP-QoL with other HR-QoL measures as well as with motor and disability assessments indicated adequate convergent validity of the scale. Gender and geographic location presented a significant impact on the PSP-QoL in our sample with women and patients from the South of Italy scoring higher than their counterparts. Conclusion: In conclusion, the Italian version of the PSP-QoL is an easy, reliable and valid tool for assessment of HR-QoL in PSP.

Background Percutaneous Endoscopic Gastrostomy (PEG) can involve some complications, despite the good safety of its track record. The Buried Bumper Syndrome (BBS) is a rare, late and dangerous complication that consists in the erosion of the internal bumper through the gastric wall. Case presentation We report the development of BBS in a man with chronic obstructive pulmonary disease (COPD) who had a persistent chronic cough which was prevalently but not solely in the morning and required placement of a PEG tube for continuous infusion of Levodopa/carbidopa intestinal gel for advanced Parkinson's disease. Conclusion We believe that COPD with chronic cough while not representing an absolute contraindication to PEG placement, may potentially cause BBS and therefore an appropriate regimen of tube care by expert personnel is mandatory in this setting.

Background erenumab was safe and effective in clinical trials for the prevention of migraine. However, real-life data are still lacking. Here we report the clinical experience from an Italian real-world setting using erenumab in patients with chronic migraine experiencing previous unsuccessful preventive treatments. Methods Seventy patients with chronic migraine and failure to ≥4 migraine preventive medication classes initially received monthly erenumab 70 mg s.c. Patients without a clinically meaningful improvement, considered as a > 30% reduction in headache days per month, after ≥3 months of therapy switched to monthly erenumab 140 mg. At the first administration and after 3 and 6 months, patients underwent extensive interviews to assess clinical parameters of disease severity and migraine-related disability and impact, and validated questionnaires to explore depression/anxiety, sleep, and quality of life (QoL). Finally, the Pain Catastrophizing Scale, Allodynia Symptom Checklist-12 and MIGraine attacks-Subjective COGnitive impairments scale (MIG-SCOG) were administered. Results 70% of patients were “responders” after the third administration of erenumab 70 mg, whereas 30% switched to erenumab 140 mg; 29% (6 pts) responded after the sixth administration. The headache-day frequency was reduced from 21.1 ± 0.7 to 11.4 ± 0.9 days after the third administration (p p Also improved were headache pain severity, migraine-related disability, and impact on daily living, QoL, pain catastrophizing and allodynia (all p p Conclusion These real-world data support monthly erenumab 70 or 140 mg s.c. as a safe and effective preventive treatment to reduce headache frequency and severity in chronic migraine patients experiencing previous unsuccessful preventive treatments.

Introduction Prospective memory is the ability to carry out a delayed intended action, so to maintain and retrieve future plans, goals and activities. Deficits of prospective memory negatively impact on patients and caregivers’ everyday living and determine poor adherence to treatment. Since frontal regions are involved in both event- and time-based prospective memory tasks and are impaired in migraine without aura, defects of prospective memory might occur in migraine without aura patients; until now this issue has not been investigated. The aim of the current study was to explore time- versus event-based prospective memory in migraine without aura. Patients and methods Ninty-one consecutive migraine without aura patients and 84 healthy subjects were enrolled in the study. They underwent a standardized measure of prospective memory evaluating both time-based and event-based prospective memory, and the Montreal Cognitive Assessment assessing global cognitive status. Moreover, all participants completed the Beck Depression Inventory-II and a self-administered version of the Apathy Evaluation Scale, to assess severity of depressive symptoms and apathy, respectively. Results Migraine without aura and healthy subjects did not differ on demographic aspects (i.e. age, education and gender). However, individuals with migraine without aura demonstrated impaired prospective memory performance compared to healthy subjects, with a greater impairment demonstrated for the time-based tasks. Within the migraine without aura group, no significant association was found between prospective memory performance and clinical scores, apathy, and depression. Conclusions Individuals with migraine without aura experience particular difficulty executing a future intention; therefore, migraine without aura is associated with dysfunction of prospective memory.

Degenerative cervical myelopathy (DCM) encompasses various pathological conditions causing spinal cord (SC) impairment, including spondylosis (multiple level degeneration), degenerative disc disease (DDD), ossification of the posterior longitudinal ligament (OPLL), and ossification of the ligamentum flavum (OLF). It is considered the most common cause of SC dysfunction among the adult population. The degenerative phenomena of DDD, spondylosis, OPLL and OLF, is likely due to both inter-related and distinct factors. Age, cervical alignment, and range of motion, as well as congenital factors such as cervical cord-canal mismatch due to congenital stenosis, Klippel-Feil, Ehler-Danlos, and Down syndromes have been previously reported as potential factors of risk for DCM. The correlation between some comorbidities, such as rheumatoid arthritis and movement disorders (Parkinson disease and cervical dystonia) and DCM, has also been reported; however, the literature remains scare. Other patient-specific factors including smoking, participation in contact sports, regular heavy load carrying on the head, and occupation (e.g. astronauts) have also been suggested as potential risk of myelopathy development. Most of the identified DCM risk factors remain poorly studied however. Further researches will be necessary to strengthen the current knowledge on the subject, especially concerning physical labors in order to identify patients at risk and to develop an effective treatment strategy for preventing this increasing prevalent disorder.

Stand-alone (SA) zero-profile implants are an alternative to cervical plating (CP) in anterior cervical discectomy and fusion (ACDF). In this study, we investigate differences in surgical outcomes between SA and CP in ACDF. We conducted a retrospective analysis of 166 patients with myelopathy and/or radiculopathy who had ACDF with SA or CP from Jan 2013–Dec 2016. We measured surgical outcomes including Bazaz dysphagia score at 3 months, Nurick grade at last follow-up, and length of hospital stay. 166 patients (92F/74M) were reviewed. 92 presented with radiculopathy (55%), 37 with myelopathy (22%), and 37 with myeloradiculopathy (22%). The average operative time with CP was longer than SA (194 ± 69 vs. 126 ± 46 min) (p &lt, 0.001), as was the average length of hospital stay (2.1 ± 2 vs. 1.5 ± 1 days) (p = 0.006). At 3 months, 82 patients (49.4%) had a follow-up for dysphagia, with 3 patients reporting mild dysphagia and none reporting moderate or severe dysphagia. Nurick grade at last follow-up for the myelopathy and myeloradiculopathy cohorts improved in 63 patients (85%). Prolonged length of stay was associated with reduced odds of having an optimal outcome by 0.50 (CI = 0.35–0.85, p = 0.003). Overall, we demonstrate that there is no significant difference in neurological outcome or rates of dysphagia between SA and CP, and that both lead to overall improvement of symptoms based on Nurick grading. However, we also show that the SA group has shorter length of hospital stay and operative time compared to CP.

IntroductionThe term placenta praevia defines a placenta that lies over the internal os, whereas the term low-lying placenta identifies a placenta that is partially implanted in the lower uterine segment with the inferior placental edge located at 1–20 mm from the internal cervical os (internal-os-distance). The most appropriate mode of birth in women with low-lying placenta is still controversial, with the majority of them undergoing caesarean section. The current project aims to evaluate the rate of vaginal birth and caesarean section in labour due to bleeding by offering a trial of labour to all women with an internal-os-distance >5 mm as assessed by transvaginal sonography in the late third trimester.Methods and analysisThe MODEL-PLACENTA is a prospective, multicentre, 1:3 matched case–control study involving 17 Maternity Units across Lombardy and Emilia-Romagna regions, Italy. The study includes women with a placenta located in the lower uterine segment at the second trimester scan. Women with a normally located placenta will be enrolled as controls. A sample size of 30 women with an internal-os-distance >5 mm at the late third trimester scan is needed at each participating Unit. Since the incidence of low-lying placenta decreases from 2% in the second trimester to 0.4% at the end of pregnancy, 150 women should be recruited at each centre at the second trimester scan. A vaginal birth rate ≥60% in women with an internal-os-distance >5 mm will be considered appropriate to start routinely admitting to labour these women.Ethics and disseminationEthical approval for the study was given by the Brianza Ethics Committee (No 3157, 2019). Written informed consent will be obtained from study participants. Results will be disseminated by publication in peer-reviewed journals and presentation in international conferences.Trial registration numberNCT04827433(pre-results stage)

Color-tunable luminescence has been extensively investigated in upconverting nanoparticles for diverse applications, each exploiting emissions in different spectral regions. Manipulation of the emission wavelength is accomplished by varying the composition of the luminescent material or the characteristics of the excitation source. Herein, we propose core-shell β-NaGdF4 : Tm3+ , Yb3+ /β-NaGdF4 : Tb3+ nanoparticles as intrinsic time-tunable luminescent materials. The time dependency of the emission wavelength only depends on the different decay time of the two emitters, without additional variation of the dopant concentration or pumping source. The time-tunable emission was recorded with a commercially available camera. The dynamics of the emissions is thoroughly investigated, and we established that the energy transfer from the 1 D2 excited state of Tm3+ ions to the higher energy excited states of Tb3+ ions to be the principal mechanism to the population of the 5 D4 level for the Tb3+ ions.

Les maladies cardiovasculaires, et en premier lieu la maladie coronarienne, restent la première cause de mortalité en Suisse. La réadaptation cardiaque intégrée est une intervention multidisciplinaire validée représentant le meilleur moyen de mettre en place une stratégie de prévention cardiovasculaire secondaire efficace pour réduire l'impact des maladies cardiovasculaires. Pourtant, moins de la moitié des patients victimes d'un infarctus du myocarde et une proportion infime de patients atteints d'une insuffisance cardiaque participent à un programme de réadaptation cardiaque dans notre pays. Cet article résume l'état actuel de la réadaptation cardiaque en Suisse ainsi que les futurs développements de téléréadaptation cardiaque qui se sont accélérés dans le contexte de la pandémie de Covid-19. Cardiovascular diseases and especially coronary artery disease remain the first cause of mortality in Switzerland. Comprehensive cardiac rehabilitation is a validated multidisciplinary intervention, which represents the most appropriate strategy of implementing an effective secondary cardiovascular prevention to reduce the impact of cardiovascular diseases. However, less than half of patients after a myocardial infarction and a tiny proportion of patients with heart failure participate in a rehabilitation program in our country. This article summarizes the current state of cardiac rehabilitation in Switzerland, as well as future developments of cardiac tele-rehabilitation that have accelerated due to the COVID-19 pandemic.