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Background Indications and outcomes in lumbar spinal fusion for degenerative disease are notoriously heterogenous. Selected subsets of patients show remarkable benefit. However, their objective identification is often difficult. Decision-making may be improved with reliable prediction of long-term outcomes for each individual patient, improving patient selection and avoiding ineffective procedures. Methods Clinical prediction models for long-term functional impairment [Oswestry Disability Index (ODI) or Core Outcome Measures Index (COMI)], back pain, and leg pain after lumbar fusion for degenerative disease were developed. Achievement of the minimum clinically important difference at 12 months postoperatively was defined as a reduction from baseline of at least 15 points for ODI, 2.2 points for COMI, or 2 points for pain severity. Results Models were developed and integrated into a web-app (https://neurosurgery.shinyapps.io/fuseml/) based on a multinational cohort [N = 817; 42.7% male; mean (SD) age: 61.19 (12.36) years]. At external validation [N = 298; 35.6% male; mean (SD) age: 59.73 (12.64) years], areas under the curves for functional impairment [0.67, 95% confidence interval (CI): 0.59–0.74], back pain (0.72, 95%CI: 0.64–0.79), and leg pain (0.64, 95%CI: 0.54–0.73) demonstrated moderate ability to identify patients who are likely to benefit from surgery. Models demonstrated fair calibration of the predicted probabilities. Conclusions Outcomes after lumbar spinal fusion for degenerative disease remain difficult to predict. Although assistive clinical prediction models can help in quantifying potential benefits of surgery and the externally validated FUSE-ML tool may aid in individualized risk–benefit estimation, truly impacting clinical practice in the era of “personalized medicine” necessitates more robust tools in this patient population.

Rapid reconfigurations of brain activity support efficient neuronal communication and flexible behaviour. Suboptimal brain dynamics is associated to impaired adaptability, possibly leading to functional deficiencies. We hypothesize that impaired flexibility in brain activity can lead to motor and cognitive symptoms of Parkinson’s disease (PD). To test this hypothesis, we studied the ‘functional repertoire’—the number of distinct configurations of neural activity—using source-reconstructed magnetoencephalography in PD patients and controls. We found stereotyped brain dynamics and reduced flexibility in PD. The intensity of this reduction was proportional to symptoms severity, which can be explained by beta-band hyper-synchronization. Moreover, the basal ganglia were prominently involved in the abnormal patterns of brain activity. Our findings support the hypotheses that: symptoms in PD relate to impaired brain flexibility, this impairment preferentially involves the basal ganglia, and beta-band hypersynchronization is associated with reduced brain flexibility. These findings highlight the importance of extensive functional repertoires for correct behaviour.

Objectives: The safest mode of delivery in low-lying placenta is debatable. Little is known about outcomes in low-lying placenta resolved during the late third trimester. We compare outcomes of women with persistent versus resolved low-lying placenta. Methods: A retrospective analysis on a prospective cohort of women with low-lying placenta confirmed at 28–30 weeks sonography (01/2009 to 03/2018). Women were followed up serially every 2 to 3 weeks until delivery to assess the placental edge-to-internal os distance (IOD), and included if scan was performed within 28 days before delivery. Results: There were 86 women: in 21 the low-lying placenta resolved, whereas in 65 persisted (n = 15 IOD 1–10 mm, n = 50 IOD 11–20 mm). Antepartum bleeding associated with higher rates of urgent cesarean delivery in 1–10 mm (P =.041) but not in 11–20 mm (P = 1.000) and >20 mm (P =.333). Among women with IOD >10 mm allowed to labor, vaginal delivery occurred in 76.7% (11–20 mm) and 94.1% (>20 mm) (P =.155), with no difference according to parity (70% and 80% in multiparas, P =.696; 60% and 72.7% in nulliparas, P =.698). Severe PPH (P =.922) and hemoglobin drop (P =.109) were similar among groups. Women with IOD 11–20 mm and >20 mm and vaginal delivery bled less than women with similarly located placenta and cesarean delivery (P =.009 and P =.048). Conclusions: Women with IOD >10 mm have high chances of deliver vaginally with no further increase of their hemorrhagic risk. Success of vaginal delivery is independent of parity and antepartum bleeding. Labor should be managed in an adequate hospital setting.

Aims Patients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality. Methods and results We used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existing heart disease and in-hospital mortality. A total of 16 511 patients with COVID-19 were included (21.1% aged 66–75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male, and often had other comorbid conditions when compared with those without. Mortality was higher in patients with cardiac disease (29.7%; n = 1545 vs. 15.9%; n = 1797). However, following multivariable adjustment, this difference was not significant [adjusted risk ratio (aRR) 1.08, 95% confidence interval (CI) 1.02–1.15; P = 0.12 (corrected for multiple testing)]. Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure (aRR 1.19, 95% CI 1.10–1.30; P Conclusion Considerable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare during hospitalization.

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.

Background Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown. Methods In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58–77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis. Results In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02–5.45], OR0.68[0.59–0.79], respectively;both pp Conclusions Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities. Trial registration CAPACITY-COVID (NCT04325412)

To address the impact of COVID-19 olfactory loss on the brain, we analyzed the neural connectivity of the central olfactory system in recently SARS-CoV-2 infected subjects with persisting olfactory impairment (hyposmia). Twenty-seven previously SARS-CoV-2 infected subjects (10 males, mean age +/- SD 40.0 +/- 7.6 years) with clinically confirmed COVID-19 related hyposmia, and eighteen healthy, never SARS-CoV-2 infected, normosmic subjects (6 males, mean age +/- SD 36.0 +/- 7.1 years), were recruited in a 3 Tesla MRI study including high angular resolution diffusion and resting-state functional MRI acquisitions. Specialized metrics of structural and functional connectivity were derived from a standard parcellation of olfactory brain areas and a previously validated graph-theoretic model of the human olfactory functional network. These metrics were compared between groups and correlated to a clinical index of olfactory impairment. On the scanning day, all subjects were virus-free and cognitively unimpaired. Compared to control, both structural and functional connectivity metrics were found significantly increased in previously SARS-CoV-2 infected subjects. Greater residual olfactory impairment was associated with more segregated processing within regions more functionally connected to the anterior piriform cortex. An increased neural connectivity within the olfactory cortex was associated with a recent SARS-CoV-2 infection when the olfactory loss was a residual COVID-19 symptom. The functional connectivity of the anterior piriform cortex, the largest cortical recipient of afferent fibers from the olfactory bulb, accounted for the inter-individual variability in the sensory impairment. Albeit preliminary, these findings could feature a characteristic brain connectivity response in the presence of COVID-19 related residual hyposmia.

Introduction Anterior odontoid screw fixation is a valid surgical option for unstable odontoid fractures, as type II Anderson D’Alonzo fractures. Grauer further divided type II fractures in subtypes according to the fracture line, providing recommendations for implementation of screw fixation techniques. Objective Primary endpoint of our study is to evaluate the postoperative results of minimally invasive odontoid screw insertion in terms of outcome, fusion rate and stability of cranio-cervical junction. Secondary endpoint was to investigate the influence of age or fractures’ features on outcome and fusion rate. Materials and methods We report the clinical and radiological features of 32 patients harbouring unstable type II fractures operated by a minimally invasive odontoid screw insertion technique. All patients underwent a high resolution multiplanar CT in order to assess fracture features according to Grauer's classification; the integrity of ligaments was investigated by MRI. In addition, a preoperative neurological performance (modified Rankin Scale, mRS) was evaluated for patients either directly or interviewing their families. Follow-up at one, three and six months and 1 year have been performed (averaging 13.5 months) by cervical CT (fusion rate and stability) and mRS update. In order to investigate the influence of age on postoperative neurological performance, two groups (≤ 50 yrs, 9 pts/ > 50 yrs, 23 pts) were separately considered and analysed. Overall, we observed no surgery related complications. We also analysed the fusion rate and its correlation with patient age and Grauer's subtype of fracture. Results At last available clinical follow-up, the preoperative performance was preserved (mRS 0/1: 24, 75%; mRS 2–4: 9, 15%) although with slight reduction of intact patients (mRS 0: 22 vs. 19; 71.8 vs. 59.3%). Younger patients (≤ 50 yrs) fared significantly better than older ones, achieving a good clinical outcome (mRS 0/1) in 100% vs. 69.5% (9/9 vs. 16/23 pts). Statistical analysis showed a fair correlation between age and outcome. Other factors such as sex and Grauer's type did not influence significantly the clinical outcome. Nine patients did not complete a full radiological follow-up and were therefore excluded from analysis of radiological outcome. Among the remaining 23 patients, only 25% of those who were followed three months or less showed fusion; conversely, all patients who have been examined from 6 to 48 months fused. Among the non-union patients, two underwent a second surgery by posterior approach. Conclusions In our recent experience, the minimally invasive AOSF proved safe and effective in treating odontoid peg fractures. Selection based on Grauer's type is mandatory to achieve best results. While in the elderly, an anterior approach is well accepted as the first choice treatment, we recommend that this option should be offered as a suitable alternative to Halo or orthosis also in younger patients since it provides prompt, excellent clinical outcome and high fusion rate especially in this age group.

Systemic Sclerosis (SSc) is a disease with limited therapeutic possibilities. Mesenchymal stem cells (MSCs)-therapy could be a promising therapeutic option, however the ideal MSCs source has not yet been found. To address this problem, we perform comparison between bone marrow (BM)-MSCs and adipose (A)-MSCs, by the miRs expression profile, to identify the gene modulation in these two MSCs source. MicroRNAs (miRs) are RNAs sequences, regulating gene expression and MSCs, derived from different tissues, may differently respond to the SSc microenvironment. The miRs array was used for the miRs profiling and by DIANA-mirPath tool we identified the biological functions of the dysregulated miRs. In SSc-BM-MSCs, 6 miRs were significantly down-regulated and 4 miRs up-regulated. In SSc-A-MSCs, 11 miRs were significantly down-regulated and 3 miRs up-regulated. Interestingly, in both the sources, the involved pathways included the senescence mechanisms and the pro-fibrotic behaviour. Furthermore, both the MSCs sources showed potential compensatory ability. A deeper knowledge of this miRs signature might give more information about some pathogenic steps of the disease and in the same time clarify the possible therapeutic role of autologous MSCs in the regenerative therapy in SSc.

Objective: To assess acceptability, efficacy, and short- and medium-term complications of vaginal misoprostol therapy for the treatment of first trimester miscarriage. Study design: A prospective cohort study including women admitted to the Unit of Obstetrics, MBBM Foundation, San Gerardo Hospital (Monza, Italy) for medical or surgical treatment of first trimester miscarriage between October 2014 and March 2018. As per Institutional protocol, patients in the medical therapy group received 800 µg of misoprostol vaginally. A second dose could be considered 3 days after the first administration if that was ineffective. Surgical treatment consisted of uterine vacuum aspiration. Success of misoprostol treatment was defined as the expulsion of the gestational sac with no need for subsequent surgery. Results: During the study period, 967 patients were diagnosed with first trimester miscarriage and were included in the study. Of these, 514 (53.2%) women were eligible for and consented to medical therapy. Surgical treatment was performed in the remaining 453 (46.8%) patients due to either medical contraindication to misoprostol or patient’s choice. Acceptance of misoprostol as first therapeutic choice increased over time, becoming the preferred treatment after approximately 18 months of use in clinical practice. One dose of misoprostol was successful in 69.8% (n = 359) of patients, whereas 20 women required urgent surgery for bleeding (n = 19) or suspected infection (n = 1). Among the remaining 135 patients, 20 (14.8%) refused the second dose of misoprostol and opted for surgery. Expulsion of the gestational sac was obtained in 74 additional cases who completed the medical protocol, for an overall success rate of 87.7% (433/494). The majority of women receiving misoprostol did not experience any short-term complication (92.0%) or side effect (93.8%). Eight (1.6%) cases requiring delayed surgery (hysteroscopy or vacuum aspiration) for retained product of conception were identified at the postmedical treatment follow up, thus leading to an actual success rate of misoprostol of 86.0% (n = 425). Conclusions: This is the first study assessing the acceptability, efficacy, and complication rate of medical management of first trimester miscarriage in an Italian tertiary care center. Our results confirm that misoprostol alone is an effective as well as a safe therapeutic option for the treatment of first trimester miscarriage.

Objective\ud We aimed to describe the prevalence and clinical-demographical features of patients with functional gait disorders (FGDs) and to compare them to patients with functional motor disorders (FMDs) without FGDs (No-FGDs).\ud \ud Methods\ud In this multicenter observational study, we enrolled patients with a clinically definite diagnosis of FMDs in 25 tertiary movement disorders centers in Italy. Each subject with FMDs underwent a comprehensive clinical assessment, including screening for different subtypes of functional gait disorders. Multivariate regression models were implemented in order to estimate the adjusted odds ratio (OR; 95% confidence interval) of having FGDs in relation to sociodemographic and clinical characteristics.\ud \ud Results\ud Out of 410 FMDs, 26.6% (n = 109) of patients exhibited FGDs. The most frequent FGDs were slow gait (n = 43, 39.4%), astasia-abasia (n = 26, 23.8%), and knee buckling (n = 24, 22%). They exhibited single FGDs in 51.4% (n = 56) or complex FGDs (more than one type of FGDs) in 48.6% (n = 53) of cases. On multivariate regression analysis, the presence of FGDs was more likely associated with older age (OR 1.03, 95% CI 1.01–1.04), functional visual symptoms (OR 2.19, 95% CI 1.08–4.45), and the diagnosis of somatic symptoms disorder (OR 2.97, 95% CI 1.08–8.17). FGDs were also more likely to undergo physiotherapy (OR 1.81, 95% CI 1.08–3.03).\ud \ud Conclusions\ud People with FMDs may present with different and overlapping types of FGDs, which may occur in older age. The association of FGDs with functional visual symptoms and somatic symptoms disorder opens up to new avenues to the understanding of the neural mechanisms of these disorders.

This quality improvement (QI) project evaluates a comprehensive, patient-centered plan to reduce the emergency department (ED) revisit rate by improving outpatient follow-up after initial ED visits. Patients with low-acuity complaints discharged from the ED are often instructed to schedule a follow-up appointment with their primary care team or a specialty service after leaving the ED. In this QI project, patients either had a follow-up visit scheduled at the time of ED discharge or received a phone call within 2 days of discharge to schedule outpatient follow-up visit. The number of ED visits per patient was significantly reduced following implementation of scheduling at the time of ED discharge.

Background and purpose Wide-necked brain aneurysms therapy remains a challenge for neurointerventionalists, mainly for the high recurrence rate. Low-profile stents make feasible the treatment of these aneurysms. In our multicenter series we analyzed clinical and angiographic results of Neuroform Atlas stent-assisted coiling. Materials and methods From January 2016 to March 2017, 113 wide-necked aneurysms were discovered with CTA, MRA and DSA. The Atlas stent-assisted coiling procedures were performed under general anesthesia with sequential or jailing techniques. Six months follow-up DSA was performed to assess the recurrence rate through the modified Raymond-Roy occlusion scale (RROC). Moreover, patients were evaluated clinically to analyse the degree of disability according to the mRS. MRI was performed at 12 months evaluating both the cerebral tissue and the vessels. Results In all the procedures it was feasible to navigate the Neuroform Atlas to the goal vessel and deploy the stent across the aneurysmal neck. Intra-procedural complications account for the 6.2% (7/113). The immediate occlusion rate was RROC 1 in 88%, 2 in 9% and 3 in 3% of cases. The 6 months clinical data showed mRS Score 0–1 in 96.5% of patients; 3 patients died of complications related to SAH. The 12 months follow-up showed RROC of 1 in 82%, 2 in 13% and 3 in 5% of cases. No aneurysm has been retreated. Conclusions In our multicenter experience the Neuroform Atlas stent assisted-coiling has shown to be a safe and effective technique for the treatment of wide-necked intracranial aneurysms with encouraging clinical and angiographic results.

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.

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). 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. The participants had an average age of 51 years and 53% were female. Median Lp(a) levels were 62 mg/L, and the 90 th percentile 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 < .001), LDL-C (1%, p = .001), and two SNPs (39%, p value-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. 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.

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.

The study presents a qualitative and culturally-sensitive investigation of the lived experiences of the forced migration of six Nigerian asylum seekers, three men and three women, hosted in Italy. Through a focus on gender identity issues, the study aimed to explore possible gender differences between participants and define their specific needs, requirements and characteristics. Overall, the gender-focused perspective through which we explored participants’ subjective experiences has enriched our understanding of their unique life stories, shedding light on the psychic dimensions as well as on the social and cultural inscriptions of their gender identity and providing insights on the different ways in which Nigerian women and men made sense of their experiences of displacement, migration, violence and trauma.

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.

Introduction: Autologous and heterologous assisted reproductive technology (ART) conceptions have been on the rise for the last few decades and alongside with that have the rate of multiple pregnancies. Multiple gestations are associated with high odds of gestational complications and, in turn, adverse delivery and feto-neonatal outcomes. Whether ART-conception further increases such elevated risk is still debated. ART is more commonly accessed by older women with chronic diseases, which relate to heightened likelihood of complications. We decided to investigate the influence of autologous and heterologous ART conception compared to spontaneous conception on delivery and feto-neonatal outcomes of diamniotic twin pregnancies in a cohort of healthy women with no chronic conditions or gestational complications. Materials and methods: Retrospective cohort study among diamniotic twin pregnancies in mothers without pregestational or gestational disease. Delivery and feto-neonatal outcomes were compared among three groups according to mode of conception: (1) spontaneous conception (SC, referent group, n = 251 pregnancies), (2) autologous ART-conception (A-ART, n = 87), and (3) heterologous ART-conception (H-ART, n = 22). Results: At adjusted analyses, twin pregnancies conceived by A-ART showed a twofold heightened risk of delivery by urgent/emergent cesarean section, as well as four and sevenfold increase in odds of blood loss >1000 and >1500 mL, respectively. H-ART pregnancies were at fivefold higher risk of undergoing prelabor cesarean section compared to SC, whereas no differences were identified for odds of severe post-partum hemorrhage. Also, A-ART and H-ART gestations displayed fetal and neonatal outcomes similar to SC pregnancies when analysis was adjusted for relevant confounding factors. Conclusion: Our results suggest that both A-ART and H-ART conception associate with increased odds of operative delivery among diamniotic twin pregnancies in healthy mothers with no chronic diseases or gestational complications. Also, a higher risk of severe postpartum hemorrhage appears to relate to A-ART independent of mode of delivery and maternal age. Further studies with larger series of uncomplicated twin pregnancies are warranted to improve our understanding of the relationship of ART to adverse delivery outcomes.

Introduction: Psychological factors can underlie fatigue in neurological disorders, but its relationship to fatigue in Parkinson's disease (PD) has not been explored. We assessed the association between maladaptive metacognitive beliefs and presence of fatigue in PD. Methods: Ninety-eight consecutive outpatients with PD (61% male; median age: 66.50 years) were assessed in terms of demographic, clinical, medication treatment, cognitive, or behavioural characteristics including metacognitive beliefs (Metacognitions Questionnaire-30 or MCQ). Fatigue was ascertained by PD-related diagnostic criteria. Univariate statistical approach (Mann-Whitney and Pearson chi-square tests) was used to compare PD patients with (f-PD) or without (nf-PD) fatigue in terms of demographic, clinical, medication treatment, cognitive, behavioural, and metacognitive measures. Results: Twenty-one PD patients (21%) displayed fatigue. The f-PD group scored higher on the MCQ-total score, MCQ-Cognitive Confidence subscale, and all behavioral measures (ps < 0.01) relative to nf-PD. They also had a more advanced Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale-III score. Conclusion: Maladaptive metacognitive beliefs such as the lack of cognitive confidence may play a key role to trigger and maintain fatigue in PD. Future studies, using a multivariate statistical approach, are needed to confirm these preliminary findings in a larger sample of patients with fatigue and to assess if modification of such metacognitive beliefs has the potential to ameliorate fatigue in PD.

The analysis of health determinants in the student population can be useful in raising awareness on safe living conditions in new generations. The selection of specific biomedical markers, like advanced glycation end products (AGEs), and the analysis of social behaviors can support lifestyle choices evaluation. A questionnaire, containing an anamnestic section, a physical activity evaluation section, and a sociological section, was administered to a total of 110 students from two Italian universities, selected from the Faculty of Science of Movement and from the Faculty of Medicine. In addition, all subjects recruited in this study underwent to an AGEs accumulation assessment through skin autofluorescence. A non-hierarchical cluster analysis was performed on the collected data allowed the identification of two group of students: group 1 mainly consisted of male subjects from the Faculty of Science of Movement, characterized by an active lifestyle and a rather detached affective family condition; group 2 largely consisted of female subjects from the Faculty of Medicine, more sedentary and with stable relationships. The data analysis confirmed the correlation between low AGEs levels and healthy lifestyles, but at the same time underlined divergences between students from different Faculties.

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.

The emerging science of fatigue has soundly endorsed the need for its unified definition, shared terminology and increased recognition in neurological illnesses. Nevertheless, the real impact of fatigue remains under-recognized. Fatigue describes a sense of tiredness, lack of energy or need for increased effort often perceived as overwhelming, pervasive, and disabling. It is a common feature of chronic medical conditions and neurological diseases, including Parkinson's disease (PD) and other hypokinetic, hyperkinetic, and functional movement disorders (FMD). While there is solid evidence for the burden of fatigue in PD, knowledge of fatigue in other movement disorders (MDS) is still limited. Lack of consensus definition, rigorous measures and the high prevalence of potential confounders such as apathy, depression and sleepiness are the main obstacles in studying fatigue in MDS. This review of the prevalence, impact, and clinical correlates of fatigue in common MDS summarizes current hypotheses for the pathophysiological mechanisms underlying fatigue and gives a brief overview of treatment options. Fatigue is a prevalent, disabling, primary non-motor symptom (NMS) in MDS, including atypical and secondary parkinsonisms, dystonia, essential tremor (ET) and a hallmark feature of FMD. We report the hypothesis that fatigue is a perceptual disorder of the sensorimotor system. Given the relevance of this burdensome symptom, fatigue deserves greater clinical and research attention to better understand its manifestation and pathophysiology and to improve diagnosis and treatment.

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: Safinamide modulates both dopaminergic and glutamatergic systems with positive effects on motor and non-motor symptoms of Parkinson's disease (PD). The drug utilization study SYNAPSES was designed to investigate the use of safinamide in routine clinical practice, as recommended by the European Medicines Agency. Objective: To describe the occurrence of adverse events in PD patients treated with safinamide in real-life conditions. Methods: The SYNAPSES trial is an observational, European, multicenter, retrospective-prospective cohort study. Patients were followed up to 12 months with analyses performed in the overall population and in patients aged >75 years, with relevant comorbidities and with psychiatric conditions. Results: Of the 1610 patients included, 82.4% were evaluable after 12 months with 25.1% of patients >75 years, 70.8% with relevant comorbidities and 42.4% with psychiatric conditions. During observation 45.8% patients experienced adverse events, 27.7% patients had adverse drug reactions and 9.2% patients had serious adverse events. The adverse events were those already described in the patients' information leaflet. The majority were mild or moderate and completely resolved and no differences were detected between the subgroup of patients. Clinically significant improvements were seen in the UPDRS motor score and in the UPDRS total score in >= 40% of patients, according to the criteria developed by Shulman et al. Conclusion: The SYNAPSES study confirms the good safety profile of safinamide even in special groups of patients. Motor complications and motor scores improved with clinically significant results in the UPDRS scale maintained in the long-term.

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.

Despite recent advances, the causes of and effective therapies for pediatric chronic cholestatic diseases remain elusive, and many patients progress to liver failure and need liver transplantation. Malnutrition is a common complication in these patients and is a well-recognized, tremendous challenge for the clinician. We undertook a narrative review of both recent and relevant older literature, published during the last 20 years, for studies linking nutrition to pediatric chronic cholestasis. The collected data confirm that malnutrition and failure to thrive are associated with increased risks of morbidity and mortality, and they also affect the outcomes of liver transplantation, including long-term survival. Malnutrition in children with chronic liver disease is multifactorial and with multiple potential nutritional deficiencies. To improve life expectancy and the quality of life, patients require careful assessments and appropriate management of their nutritional statuses by multidisciplinary teams, which can identify and/or prevent specific deficiencies and initiate appropriate interventions. Solutions available for the clinical management of these children in general, as well as those directed to specific etiologies, are summarized. We particularly focus on fat-soluble vitamin deficiency and malnutrition due to fat malabsorption. Supplemental feeding, including medium-chain triglycerides, essential fatty acids, branched-chain amino acids, and the extra calories needed to overcome the consequences of anorexia and high energy requirements, is reviewed. Future studies should address the need for further improving commercially available and nutritionally complete infant milk formulae for the dietary management of this fragile category of patients. The aid of a specialist dietitian, educational training regarding nutritional guidelines for stakeholders, and improving family nutritional health literacy appear essential.

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 Monoclonal antibodies (mABs) against calcitonin gene-related peptide (CGRP) or its receptor have emerged as effective and well-tolerated preventive medications for migraine. The key role played by CGRP has been recently demonstrated also in the pathophysiology of cluster headache (CH), paving the way for studies aimed to investigate the effectiveness of mABs targeting CGRP also in CH. However, no trials have been conducted so far to test the efficacy and tolerability of erenumab as CH preventive treatment. Case series We describe the cases of 5 patients with both migraines and CH with previous failures of preventive treatments. All patients were treated with monthly erenumab (70 or 140 mg) showing good results not only on migraine but also on CH attacks frequency and intensity. Improvements of both intensity and frequency of CH attacks occurred only after at least 3 months of treatment, with monthly erenumab 140 mg, suggesting that longer treatment and higher doses are needed in CH in comparison to migraine. Discussion and conclusion Our findings support the efficacy and tolerability of monthly erenumab 140 mg as a preventive treatment in patients suffering from both migraines without aura and CH. We speculate that erenumab could represent a low-risk alternative for CH patients (with or without comorbid migraine) who did not tolerate common CH preventatives therapies or for whom the therapies were not successful. Certainly, randomized trials are needed to confirm these observations and we hope that our data, showing a delayed therapeutic effect only with the highest dose of erenumab (140 mg/month), can be taken into account in designing future trials.

Introduction: Previous studies on Parkinson's disease (PD) have shown that memory complaints and fatigue co-occur since premotor stages of disease, but whether Subjective Memory Decline (SMD, defined as memory complaints with normal objective cognitive performance) and fatigue were associated in PD has not been explored yet. Methods: One-hundred PD patients underwent measures of memory complaints (Multifactorial Memory Questionnaire, MMQ), neuropsychological test (Parkinson's Disease-Cognitive Rating Scale), and assessment of behavioural symptoms. Fatigue was diagnosed according to current diagnostic criteria. Mann-Whitney test or Pearson chi-square test were used to compare fatigued and nonfatigued patients for prevalence of SMD and for demographic, clinical, and behavioural features, memory complaint, and objective cognitive measures. The confounding effect of sample's features on results was controlled by logistic regression and Quade's rank analysis. Results: Twenty-three patients were diagnosed as fatigued whereas 15 patients met SMD criteria. Fatigued patients showed higher levodopa equivalent daily dose and more marked behavioural symptoms than nonfatigued patients (ps < 0.01). The prevalence of SMD was higher in fatigued patients than in those nonfatigued (35% vs 9%, p < 0.01). After controlling for confounds, the patients with fatigue had an odds ratio for SMD 5.97 [CI 95%, 1.18–30.03] times higher and presented significantly lower scores on Contentment subscales of MMQ (p < 0.01) than those without fatigue. Conclusion: Fatigue in PD is associated with SMD mainly characterized by less contentment with one's own memory ability. These findings suggest possible shared pathogenic mechanisms underlying these two nonmotor manifestations and foster to identify potential phenotypes of patients requiring multistrategic therapeutic approaches.

Introduction: Fatigue is one of the most common and disabling nonmotor symptom in Parkinson's disease (PD). The aim of the present study was to investigate the 1-year course of fatigue in a consecutive sample of de novo drug-naïve patients with PD, and at systematically searching for baseline motor and nonmotor predictors associated with fatigue severity over time. Methods: Fifty-five consecutive de novo PD patients (age: 64.71 ± 7.74 years) underwent a comprehensive examination, including Parkinson Fatigue Scale, Epworth Sleepiness Scale, Parkinson's Disease Sleep Scale, Beck Depression Inventory, Parkinson's Anxiety Scale, Apathy Evaluation Scale, and an extensive neuropsychological evaluation. Bivariate and multiple regression analyses were performed to identify baseline predictors independently related to fatigue severity at 1-year follow-up. Results: Prevalence rate of fatigue (defined by PFS cut-off) increased from 22% at baseline to 38% at 1-year follow-up. A similar increase in prevalence was observed for excessive daytime sleepiness, and apathy. Among patients with fatigue at baseline, 91% had fatigue at follow-up too (i.e., persistent fatigue). Multivariate regression analysis identified fatigue (p < 0.01), daytime sleepiness (p < 0.01), and emotional apathy (p < 0.01) as the main baseline variables significantly predicting fatigue severity at 1-year follow-up. Conclusion: In early PD, fatigue increases and persists over time, and its severity is related to higher baseline levels of fatigue, excessive daytime sleepiness, and emotional apathy. These results warrant to monitor fatigue since the early stage of disease, and suggest that treating excessive daytime sleepiness and emotional apathy might prevent its worsening.

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.

The TANDEM investigation was carried out in 17 Italian Movement Disorder centers on behalf of a joint initiative of neurologist members of the Italian Academy for Parkinson’s disease and Movement Disorders (LIMPE-DISMOV Academy) and gastroenterologist members of the Italian Society of Digestive Endoscopy (SIED) to evaluate the efficacy and tolerability of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced Parkinson's disease (PD) in routine medical care. Motor scores in “ON” and OFF” state (UPDRS-III), complications of therapy (UPDRS-IV), activities of daily living, sleep disorders and quality of life were evaluated at baseline and at two follow-up assessments (FUV1 and FUV2) within the initial 12-month LCIG treatment. In 159 patients (55% males) with a mean age of 69.1 ± 6.6years and a diagnosis of PD since 13.6 ± 5.5years, the UPDRS-III total score (in “OFF”) decreased from baseline (45.8 ± 13.2) to FUV1 (41.0 ± 17.4; p < 0.001) and FUV2 (40.5 ± 15.5; p < 0.001), the UPDRS-IV total score decreased from baseline (8.8 ± 2.9) to FUV1 (5.1 ± 3.4; p < 0.001) and FUV2 (5.5 ± 3.2; p < 0.001). The percentage of patients exhibiting freezing, dystonia, gait/walking disturbances, falls, pain and sleep disorders was significantly reduced. Twenty-eight device complications were reported and 11 (6.9%) patients prematurely terminated the study. LCIG after 12-month treatment led to sustained improvement of time spent in “OFF”, complications of therapy, PD-associated symptoms and sleep disorders. LCIG tolerability was consistent with the established safety profile of LCIG.

We present a qualitative study exploring the subjective meanings that five female Nigerian asylum seekers hosted in Italy attributed to their pre-migratory, migratory and post-migratory experiences, with an examination in-depth of the gender identity dimensions. We developed and administered semi-structured interviews, analyzed according to the Interpretative Phenomenological Analysis. On the background of the identity breakdown produced by forced migration, we highlight an inadequate integration process of the gender roles of woman and mother, generating a fracture that makes women's experiences particularly fragile. Reflections on the implication of the study and of the development of intervention programs will be outlined.

Objective.Antibodies that recognize the phosphatidylserine/prothrombin complex (antiphosphatidylserine/prothrombin antibodies; aPS/PT) might reveal enhanced thrombotic risk in patients with systemic lupus erythematosus. Little is known about their association with pregnancy complications in the antiphospholipid syndrome (APS).Methods.We enrolled 55 patients with APS who were seeking pregnancy in 2 Italian hospitals. Antiphospholipid antibodies (aPL), including anticardiolipin antibodies, anti-β2-glycoprotein I antibodies, lupus-like anticoagulant, and aPS/PT antibodies were assessed, and the patients were prospectively followed for 24 months.Results.There were 65% (36/55) of the APS patients who had aPS/PT antibodies. Forty-seven pregnancies were followed, including 33 of aPS/PT+ patients. Forty-one of the 47 patients (87%) who initiated a pregnancy eventually gave birth to a child. The pregnancy duration and the mean newborn weight at delivery were significantly lower in aPS/PT+ than in aPS/PT− patients (33.1 ± 4.7 vs 36.2 ± 3.4 wks of gestation, respectively, and 2058 ± 964 g vs 2784 ± 746 g, respectively, p < 0.05). Late pregnancy complications, including intrauterine fetal death, preterm delivery, preeclampsia, and intrauterine growth restriction (IUGR), were more frequent in aPS/PT+ patients, independent of the therapy. Titers of aPS/PT IgG were significantly inversely correlated with the neonatal weight at delivery. Vascular injury, as reflected by thrombosis, fibrinoid necrosis, ischemic and hemorrhagic areas, and presence of chorangiomas characterized the IUGR placentas in the presence of aPS/PT.Conclusion.The aPS/PT antibodies might represent markers of aPL-related pregnancy complications, IUGR/preeclampsia in particular, and could help identify beforehand patients who may require additional treatment.

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.

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)

Klippel-Feil syndrome (KFS) occurs due to failure of vertebral segmentation during development. Minimal research has been done to understand the prevalence of associated symptoms. Here, we report one of the largest collections of KFS patient data. Data were obtained from the CoRDS registry. Participants with cervical fusions were categorized into Type I, II, or III based on the Samartzis criteria. Symptoms and comorbidities were assessed against type and location of fusion. Seventy-five patients (60F/14M/1 unknown) were identified and classified as: Type I, n = 21(28%); Type II, n = 15(20%); Type III, n = 39(52%). Cervical fusion by level were: OC–C1, n = 17(22.7%), C1–C2, n = 24(32%); C2–C3, n = 42(56%); C3–C4, n = 30(40%); C4–C5, n = 42(56%); C5–C6, n = 32(42.7%); C6–C7, n = 25(33.3%); C7–T1, n = 13(17.3%). 94.6% of patients reported current symptoms and the average age when symptoms began and worsened were 17.5 (± 13.4) and 27.6 (± 15.3), respectively. Patients reported to have a high number of comorbidities including spinal, neurological and others, a high frequency of general symptoms (e.g., fatigue, dizziness) and chronic symptoms (limited range of neck motion [LROM], neck/spine muscles soreness). Sprengel deformity was reported in 26.7%. Most patients reported having received medication and invasive/non-invasive procedures. Multilevel fusions (Samartzis II/III) were significantly associated with dizziness (p = 0.040), the presence of LROM (p = 0.022), and Sprengel deformity (p = 0.036). KFS is associated with a number of musculoskeletal and neurological symptoms. Fusions are more prevalent toward the center of the cervical region, and less common at the occipital/thoracic junction. Associated comorbidities including Sprengel deformity may be more common in KFS patients with multilevel cervical fusions. These slides can be retrieved under Electronic Supplementary Material.

The advent of Next Generation Sequencing technologies brought with it the discovery of several microRNA (miRNA) variants of heterogeneous lengths and/or sequences. Initially ascribed to sequencing errors/artifacts, these isoforms, named isomiRs, are now considered non-canonical variants that originate from physiological processes affecting the canonical miRNA biogenesis. To date, accurate IsomiRs abundance, biological activity, and functions are not completely understood; however, the study of isomiR biology is an area of great interest due to their high frequency in the human miRNome, their putative functions in cooperating with the canonical miRNAs, and potential for exhibiting novel functional roles. The discovery of isomiRs highlighted the complexity of the small RNA transcriptional landscape in several diseases, including cancer. In this field, the study of isomiRs could provide further insights into the miRNA biology and its implication in oncogenesis, possibly providing putative new cancer diagnostic, prognostic, and predictive biomarkers as well. In this review, a comprehensive overview of the state of research on isomiRs in different cancer types, including the most common tumors such as breast cancer, colorectal cancer, melanoma, and prostate cancer, as well as in the less frequent tumors, as for example brain tumors and hematological malignancies, will be summarized and discussed.

ObjectiveHistory of cardiovascular diseases (CVDs) may influence the prognosis of patients hospitalised for COVID-19. We investigated whether patients with previous CVD have increased risk of death and major adverse cardiovascular event (MACE) when hospitalised for COVID-19.MethodsWe included 839 patients with COVID-19 hospitalised at the University Hospitals of Geneva. Demographic characteristics, medical history, laboratory values, ECG at admission and medications at admission were collected based on electronic medical records. The primary outcome was a composite of in-hospital mortality or MACE.ResultsMedian age was 67 years, 453 (54%) were males and 277 (33%) had history of CVD. In total, 152 (18%) died and 687 (82%) were discharged, including 72 (9%) who survived a MACE. Patients with previous CVD were more at risk of composite outcomes 141/277 (51%) compared with those without CVD 83/562 (15%) (OR=6.0 (95% CI 4.3 to 8.4), pConclusionHistory of CVD is associated with higher in-hospital mortality and MACE in hospitalised patients with COVID-19. Other factors associated with higher in-hospital mortality are older age, male sex and elevated CRP on admission.

Purpose Spinal diseases requiring urgent surgical treatment are rare during pregnancy. Evidence is sparse and data are only available in the form of case reports. Our aim is to provide a comprehensive guide for spinal surgery on pregnant patients and highlight diagnostic and therapeutic aspects. Methods The study included a cohort of consecutive pregnant patients who underwent spinal surgery at five high-volume neurosurgical centers between 2010 and 2017. Perioperative and perinatal clinical data were derived from medical records. Results Twenty-four pregnant patients were included. Three underwent a preoperative cesarean section. Twenty-one patients underwent surgery during pregnancy. Median maternal age was 33 years, and median gestational age was 13 completed weeks. Indications were: lumbar disk prolapse (n = 14; including cauda equina, severe motor deficits or acute pain), unstable spine injuries (n = 4); intramedullary tumor with paraparesis (n = 1), infection (n = 1) and Schwann cell nerve root tumor presenting with high-grade paresis (n = 1). Two patients suffered transient gestational diabetes and 1 patient presented with vaginal bleeding without any signs of fetal complications. No miscarriages, stillbirths, or severe obstetric complications occurred until delivery. All patients improved neurologically after the surgery. Conclusion Spinal surgical procedures during pregnancy seem to be safe. The indication for surgery has to be very strict and surgical procedures during pregnancy should be reserved for emergency cases. For pregnant patients, the surgical strategy should be individually tailored to the mother and the fetus.

Introduction Following the severe consequences of the coronavirus disease 2019 (COVID-19) outbreak, on March 9th, 2020 the Italian Government implemented extraordinary measures to limit viral transmission, including restrictive quarantine measures. Psychological distress represents the seizure-precipitating factor most often reported by patients with epilepsy. To date, no studies have analyzed the role played by the different dimensions of psychological distress quarantine-induced in patients with epilepsy. Materials and Methods We included a total of 40 patients, 18 suffered from generalized, and 22 from focal epilepsy. The patients previously seen in the outpatient clinic during the pre-lockdown period between January and February 2020 were reevaluated after the lockdown period. Psychological distress was evaluated by using the three subscales of Impact of Event Scale-Revised (IES-R). Finally, we employed logistic regression analyses to explore the demographic and clinical features associated to high scores on IES-R. Results Patients with higher scores on IES-R Intrusion and IES-R Avoidance subscales demonstrated an increased number of epileptic attacks compared to prelockdown period. Multivariate logistic regression analyses showed that a specific subgroup of patients (i.e., older, female with more anxious symptoms) are at higher risk of increased seizure frequency. Conclusions Our study confirmed that the frequency of epileptic seizures increased during lockdown when compared to pre-lockdown period. The early identification of patients more vulnerable to worsening is crucial to limit the risk of requiring hospital or clinical treatment during the COVID-19 outbreak.

Introduction To investigate intrinsic neural networks connectivity changes in Parkinson's disease (PD) patients with and without impulse control disorders (ICD). Methods Fifteen patients with PD with ICD (ICD+), 15 patients with PD without ICD (ICD−) and 24 age and sex-matched healthy controls (HC) were enrolled in the study. To identify patients with and without ICD and/or punding, we used the Minnesota Impulsive Disorders Interview (MIDI) and a clinical interview based on diagnostic criteria for each symptom. All patients underwent a detailed neuropsychological evaluation. Whole brain structural and functional imaging was performed on a 3T GE MR scanner. Statistical analysis of functional data was completed using BrainVoyager QX software. Voxel-based morphometry (VBM) was used to test whether between-group differences in resting-state connectivity were related to structural abnormalities. Results The presence of ICD symptoms was associated with an increased connectivity within the salience and default-mode networks, as well as with a decreased connectivity within the central executive network (p < .05 corrected). ICD severity was correlated with both salience and default mode networks connectivity changes only in the ICD+ group. VBM analysis did not reveal any statistically significant differences in local grey matter volume between ICD+ and ICD− patients and between all patients and HC (p < .05. FWE). Conclusions The presence of a disrupted connectivity within the three core neurocognitive networks may be considered as a potential neural correlate of ICD presence in patients with PD. Our findings provide additional insights into the mechanisms underlying ICD in PD, confirming the crucial role of an abnormal prefrontal-limbic-striatal homeostasis in their development.

To investigate the reliability of a new in-house automatic algorithm for calculating the Magnetic Resonance Parkinsonism Index (MRPI), in a large multicentre study population of patients affected by progressive supranuclear palsy (PSP) or Parkinson’s disease (PD), and healthy controls (HC), and to compare the diagnostic accuracy of the automatic and manual MRPI values. The study included 88 PSP patients, 234 PD patients and 117 controls. MRI was performed using both 3T and 1.5T scanners. Automatic and manual MRPI values were evaluated, and accuracy of both methods in distinguishing PSP from PD and controls was calculated. No statistical differences were found between automated and manual MRPI values in all groups. The automatic MRPI values differentiated PSP from PD with an accuracy of 95 % (manual MRPI accuracy 96 %) and 97 % (manual MRPI accuracy 100 %) for 1.5T and 3T scanners, respectively. Our study showed that the new in-house automated method for MRPI calculation was highly accurate in distinguishing PSP from PD. Our automatic approach allows a widespread use of MRPI in clinical practice and in longitudinal research studies. • A new automatic method for calculating the MRPI is presented. • Automatic MRPI values are in good agreement with manual values. • Automatic MRPI can distinguish patients with PSP from patients with PD. • The automatic method overcomes MRPI application limitations in routine practice. • The automatic method may allow a more widespread use of MRPI.

OBJECTIVES The aim of this study was to assess the postoperative outcomes of robotic-assisted lobectomy in obese patients to determine the impact of the robotic approach on a high-risk population who were candidates for major pulmonary resection for non-small-cell lung cancer (NSCLC). METHODS Between January 2007 and August 2018, we retrospectively reviewed the medical records of 224 obese patients (body mass index ≥ 30) who underwent pulmonary lobectomy at our institution via robotic-assisted thoracic surgery (RATS, n = 51) or lateral muscle-sparing thoracotomy (n = 173). RESULTS Forty-two patients were individually matched with those who had the same pathological tumour stage and similar comorbidities and presurgical treatment. The median operative time was significantly longer in the RATS group compared to that in the thoracotomy group (200 vs 158 min; P = 0.003), whereas the length of stay was significantly better for the RATS group (5 vs 6 days; P = 0.047). Postoperative complications were significantly more frequent after open lobectomy than in the RATS group (42.9% vs 16.7%; P = 0.027). After a median follow-up of 4.4 years, the 5-year overall survival rate was 67.6% [95% confidence interval (CI) 45.7–82.2] for the RATS group, and 66.1% (95% CI 46.8–79.9) for the open surgery group (log-rank P = 0.54). The 5-year cumulative incidence of cancer-related deaths was 24.8% (95% CI 9.7–43.5) for the RATS group and 23.6% (95% CI 10.8–39.2) for the open surgery group (Gray’s test, P = 0.69). CONCLUSIONS RATS is feasible and safe for obese patients with NSCLC with advantages compared to open surgery in terms of early postoperative outcomes. In addition, the long-term survival rate was comparable to that of the open approach.

Background This study analyzed the short- and long-term outcomes of robotic-assisted thoracic surgery (RATS) for early stage non-small cell lung cancer (NSCLC). Methods From November 2006 to December 2016, we performed 363 RATS procedures. This study retrospectively reviewed 339 patients who underwent RATS for clinical stages I (n = 318) or II (n = 21) NSCLC. Results Twenty-nine patients underwent segmentectomy, 307 lobectomy, and 3 pneumonectomy. Conversion occurred in 22 patients (6.5%): 15 (4.4%) due to technical issues, 4 (1.2%) for oncological reasons, and 3 (0.9%) for bleeding. The median number of N1 and N2 stations resected was 2 and 3, respectively, and the median number of N1 and N2 lymph nodes resected was 9 and 6, respectively. Median operative time was 192 minutes for lobectomy, 172 minutes for segmentectomy, and 275 minutes for pneumonectomy. Median length of hospital stay was 5 days (2–191). The most common postoperative complication was prolonged air leak (12.1%). Major complications occurred in eight patients (2.4%). The 30-day and 90-day operative mortality was 0% and 0.3%, respectively. Two and 5-year cancer-specific survival rate was 96.1% and 91.5%, respectively. Five-year survival rate was 96.2% for patients who underwent segmentectomy, and 89.1% for lobectomy. All three patients who underwent pneumonectomy were alive at 5 years with no disease. Conclusions Besides the well-known short-term outcomes showing very low morbidity and mortality rates, mediastinal lymph node dissection during RATS adequately assesses lymph node stations detecting occult lymph node metastasis and leading to excellent oncologic results. However, these results await longer follow-up studies.

Background: Sex difference is related to specific clinical features in PD patients over the disease course. Objectives: To investigate the potential sex-difference effect on the spontaneous neuronal activity within the most reported resting-state networks in early untreated PD patients and its correlation with baseline and longitudinal clinical features. Methods: Fifty-six drug-naïve PD patients (30/26 male/female) and 30 (15/15 male/female) matched controls were enrolled in the study. Topological and spectral resting-state functional MRI features of the sensorimotor, dorsal and ventral attention, frontoparietal, and default-mode networks were analyzed for possible sex-difference effects in both PD patients and controls groups. Additionally, a region-of-interest analysis was performed to test for a sex effect on basal ganglia connectivity. Multivariate ordinal regression was used to investigate whether connectivity findings at baseline were predictors of motor impairment over a 2-year follow-up period. Results: Compared to female PD patients and controls, male PD patients showed an abnormal spectral composition of the sensorimotor and dorsal attention networks in the slow-5 band. The region-of-interest analysis showed an increased connectivity within the basal ganglia in female PD patients compared to males. Functional sensorimotor connectivity changes at baseline showed to be an independent predictor of disease severity at 2-year follow-up. Conclusions: Our findings revealed the presence of a disease-related, sex-specific cortical and subcortical connectivity pattern within the sensorimotor network, in the early stage of PD. We hypothesize that these findings may be related to the presence of different sex-specific nigrostriatal dopaminergic pathways and might predict PD progression. © 2019 International Parkinson and Movement Disorder Society.

Introduction The Fatigue Severity Scale (FSS-9) and the Parkinson Fatigue Scale (PFS-16) are commonly used for assessing fatigue in Parkinson's disease (PD). Here we validated the Italian version of these scales, assessed their psychometric properties by Rasch analysis, and computed their optimal cut-off scores using clinical diagnosis of PD-related fatigue as the gold standard. Methods PD patients (n = 167) completed the Italian versions of FSS-9 and PFS-16. Each item of PFS-16 was scored both on a 5-point (PFS-16polytomous) and on a 2-point scale (PFS-16dichotomous). Results All scales showed an adequate overall Rasch model fit, high reliability, and good discriminant, convergent, and concurrent validity, but were less accurate in measuring very high and very low fatigue levels. No evidence of differential item functioning with respect to age, sex, and severity of parkinsonian symptoms was found. Some items of FSS-9 (item 1), PFS-16polytomous (items 1 and 13), and PFS-16dichotomous (items 1, 8, and 13) showed misfit, possibly due to their content concerning sleep and motivation disorders. When FSS-9 and PFS-16polytomous’ responses were rescored on a 3-point scale, the discriminability across response categories improved. The optimal cut-off score in detecting clinically-diagnosed fatigue (observed in 20% of the sample) was 3.09 for PFS-16polytomous, 8.00 for PFS-16dichotomous, and 4.67 for FSS-9. Conclusions The Italian version of PFS-16 and FSS-9 showed sound psychometric properties and can be confidently used to quantify fatigue symptoms in PD, although clinical diagnosis of fatigue should rely on validated criteria. The PFS-16polytomous exhibited advantages with respect to PFS-16dichotomous.

Progressive supranuclear palsy (PSP) is a rare, rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. Caring for a partner or relative who suffers from PSP entails a strenuous and demanding task, usually lasting for years that affects carers’ everyday life routines and emotional and social well-being. The 26-item Parkinsonism Carers QoL (PQoL Carer) is a self-administered, concise instrument evaluating the quality of life of caregivers of patients with atypical parkinsonism (both PSP and multiple system atrophy). Here, the PQoL Carer was translated into Italian and validated in 162 carers of PSP patients (54.3% women; mean age (standard deviation), 62.4 (15.4)) diagnosed according to the Movement Disorder Society criteria and recruited in 16 third-level movement disorders centers participating in the Neurecanet project. The mean PQoL total score was 40.66 ± 19.46. The internal consistency was excellent (Cronbach’s alpha = 0.941); corrected item-total correlation was > 0.40 for all the items. A correlation with other health-related quality of life measures as well as with behavioral assessments was shown suggesting adequate convergent validity of the scale. PQoL also correlated with patients’ severity of disease. The discriminant validity of the scale was evidenced by its capacity to differentiate between carers with varying levels of self-reported health (p < 0.001). In conclusion, the Italian version of the PQoL Carer is an easy, consistent, and valid tool for the assessment of the quality of life in carers of PSP patients.

Background. In the context of a causal relationship between stress and migraine, coping strategies are aimed at managing stressful life events and reducing the distressing emotions connected to them. Methods. Sixty-one consecutive patients with migraine without aura (MwoA) and sixty-one healthy controls (HCs) completed three self-report questionnaires assessing a broad range of coping (cognitive and behavioural) strategies: the Coping Orientation to Problems Experienced (COPE), the Coping Inventory for Stressful Situation (CISS), and the Proactive Coping Inventory (PCI). Moreover, the Perceived Stress Scale (PSS), a scale measuring self-perception of stress, global cognitive functioning, depressive symptoms, apathy, state, and trait anxiety, was administered to all participants. Results. No significant difference was found on the scales and subscales of PCI and CISS as well as in the PSS between MwoA patients and HCs. However, the two groups showed different scores in the subscale “turning to religion” of COPE (22.08±5.19 in migraineurs vs. 24.70±4.44 in HCs, p=0.003). A significant negative correlation of the turning to religion score with the HIT-6 score was found. Conclusions. The present study revealed that MwoA patients show a significantly reduced use of the “turning to religion” approach, an emotion-focused coping strategy. Although migraine patients appeared to be less oriented to transcendent (that means a reduced utilization of an adaptive coping strategy), they did not perceive daily living as more stressful than HCs. Finally, the reduced utilization of the “turning to religion” coping strategy is associated with a great impact of migraine on ability to function on the job or at school, at home, and in social situations in migraine patients.