Metabolic and molecular effects of dietary extra virgin olive oil in blood and placenta of women with GDM.

Gestational diabetes mellitus (GDM) increases the risks of maternal, placental, and neonatal complications. Previously, we found that a diet enriched in extra virgin olive oil (EVOO) prevents increased maternal triglyceridemia and placental proinflammatory markers in a cohort of GDM patients. The aim of this work was to evaluate maternal circulating markers of insulin resistance, placental collagen, glycogen and lipid levels, and placental levels of proteins, mRNAs, and a microRNA involved in the endocytic pathway in the same cohort of control women and women with GDM who received or did not receive a diet enriched in EVOO (36 g/day) from weeks 24 to 28 of pregnancy until term. Results: At term, the TG/HDL cholesterol ratio, fatty acid binding protein 4 circulating levels, and maternal BMI were increased in the GDM patients, alterations prevented by the maternal diet enriched in EVOO. Although there were no changes in placental lipid levels and lipid profile, GDM placentas were thicker than controls and showed increased glycogen and collagen content, alterations prevented by the EVOO enriched diet. GDM placentas showed increases in megalin levels, in the expression of several genes involved in the endocytic pathway, and in miR-199, which targets these genes, alterations prevented by the maternal diet enriched in EVOO. Conclusions: We identified novel beneficial effects of an EVOO-enriched diet in GDM women, a diet capable of regulating maternal insulin resistance, the structure and metabolism of the placenta, and the placental endocytic pathway, suggesting effects that may be beneficial for fetal development.

Clinical and Visual Outcomes of Dysthyroid Optic Neuropathy After Surgical Orbital Decompression.

Background: Current guidelines suggest high-dose steroids as first-line treatment for dysthyroid optic neuropathy (DON). When steroids fail, decompressive surgery is mandatory. Methods: We conducted a single-center, retrospective cohort study in a tertiary care combined Thyroid-Eye clinic in Milan, Italy. We studied 88 orbits of 56 patients that were submitted to surgical orbital decompression to treat DON from 2005 to 2020. Of these, 33 orbits (37.5%) underwent surgery as first-line treatment for DON whereas the other 55 (62.5%) were decompressed after being unresponsive to very high-dose steroids. Previous orbital surgery, concurrent neurological or ophthalmologic diseases, or incomplete follow-up were considered as exclusion criteria from this study. Surgery was considered successful if no further decompression was needed to preserve vision. Pinhole best corrected visual acuity (p-BCVA), color sensitivity, automated visual field, pupil reflexes, optic disk and fundus appearance, exophtalmometry, and ocular motility were studied before and after surgery (1 week, 1, 3, 6, and 12 months). Activity of Graves' Orbitopathy (GO) was graded using a clinical activity score (CAS). Results: Surgery was successful in 77 orbits (87.5%). The remaining 11 orbits (12.5%) needed further surgery to treat DON definitively. All parameters of visual function improved significantly at follow-up and GO inactivated (CAS <3) within 1 month. At 3 months, all 77 responding orbits had p-BCVA >0.63 whereas all of the 11 non-responding orbits had p-BCVA ≤0.63. Visual field parameters and color sensitivity were not associated with response to surgery. High-dose steroid treatment before surgery was associated with a better response rate (96% vs. 73%; p = 0.004). Balanced decompression was associated with a higher response rate compared with medial wall decompression (96% vs. 80%; p = 0.04). A significant inverse correlation was observed between final p-BCVA and the patient's age (r = -0.42; p = 0.0003). Conclusions: Surgical decompression was found to be a very effective treatment for DON. In this study, all clinical parameters improved after surgery and further intervention was rarely needed.

Protective Effect of Limosilactobacillus fermentum ME-3 against the Increase in Paracellular Permeability Induced by Chemotherapy or Inflammatory Conditions in Caco-2 Cell Models.

Chemotherapy- or inflammation-induced increase in intestinal permeability represents a severe element in disease evolution in patients suffering from colorectal cancer and gut inflammatory conditions. Emerging data strongly support the gut microbiota's role in preserving intestinal barrier integrity, whilst both chemotherapy and gut inflammation alter microbiota composition. Some probiotics might have a strong re-balancing effect on the gut microbiota, also positively affecting intestinal barrier integrity. In this study, we asked whether Limosilactobacillus fermentum ME-3 can prevent the intestinal paracellular permeability increase caused by the chemotherapeutic drug Irinotecan or by inflammatory stimuli, such as lipopolysaccharide (LPS). As an intestinal barrier model, we used a confluent and polarized Caco-2 cell monolayer and assessed the ME-3-induced effect on paracellular permeability by transepithelial electrical resistance (TEER) and fluorescent-dextran flux assays. The integrity of tight and adherens junctions was examined by confocal microscopy analysis. Transwell co-cultures of Caco-2 cells and U937-derived macrophages were used as models of LPS-induced intestinal inflammation to test the effect of ME-3 on release of the pro-inflammatory cytokines Tumor Necrosis Factor α, Interleukin-6, and Interleukin-8, was measured by ELISA. The results demonstrate that ME-3 prevents the IRI-induced increment in paracellular permeability, possibly by modulating the expression and localization of cell junction components. In addition, ME-3 inhibited both the increase in paracellular permeability and the release of pro-inflammatory cytokines in the co-culture model of LPS-induced inflammation. Our findings sustain the validity of L. fermentum ME-3 as a valuable therapeutic tool for preventing leaky gut syndrome, still currently without an available specific treatment.

Technologies to support the diagnosis and/or treatment of neurodevelopmental disorders: A systematic review.

In recent years, there has been a great interest in utilizing technology in mental health research. The rapid technological development has encouraged researchers to apply technology as a part of a diagnostic process or treatment of Neurodevelopmental Disorders (NDDs). With the large number of studies being published comes an urgent need to inform clinicians and researchers about the latest advances in this field. Here, we methodically explore and summarize findings from studies published between August 2019 and February 2022. A search strategy led to the identification of 4108 records from PubMed and APA PsycInfo databases. 221 quantitative studies were included, covering a wide range of technologies used for diagnosis and/or treatment of NDDs, with the biggest focus on Autism Spectrum Disorder (ASD). The most popular technologies included machine learning, functional magnetic resonance imaging, electroencephalogram, magnetic resonance imaging, and neurofeedback. The results of the review indicate that technology-based diagnosis and intervention for NDD population is promising. However, given a high risk of bias of many studies, more high-quality research is needed.

Stability of a standardized preparation of methotrexate, cytarabine, and methylprednisolone hemisuccinate for intrathecal use.

INTRODUCTION: Data about the feasibility or stability of drugs prepared for intrathecal administration are scarce, especially concerning the possibility of mixing two or more compounds in the same syringe. We evaluated the stability of an extemporaneously prepared triple intrathecal therapy containing methotrexate, cytarabine, and methylprednisolone hemisuccinate. MATERIALS AND METHODS: Six mixtures containing 12.5 mg methotrexate, 50 mg cytarabine, and 40 mg methylprednisolone hemisuccinate, diluted to a final volume of 5 ml with water for injection, were prepared in polypropylene syringes on six different days. Syringes were stored protected from light either at room temperature (20°C) (n = 3) or refrigerated temperature (4°C) (n = 3). Samples were analyzed immediately after preparation and again at 0.5, 2, 4, 6, 8, and 24 h. The analysis was conducted with a high-performance liquid chromatography instrument equipped with a quaternary pump and diode array detector. pH was also assessed before every sample analysis. RESULTS: When mixed in a polypropylene syringe, the three drugs were stable at both temperatures tested. No degradation >10% was observed in any sample and pH remained between 7.0 and 7.5 over time. No precipitation or color change occurred. Among the three compounds, methylprednisolone hemisuccinate was the most labile as a slight temperature- and time-dependent degradation was observed. CONCLUSION: Triple intrathecal solution of methotrexate, cytarabine, and methylprednisolone hemisuccinate is stable for up to 24 h when stored in polypropylene syringes protected from light at 4°C and 20°C.

Recent Considerations on Gaming Console Based Training for Multiple Sclerosis Rehabilitation.

Multiple Sclerosis (MS) is a well-known, chronic demyelinating disease of the Central Nervous System (CNS) and one of the most common causes of disability in young adults. In this context, one of the major challenges in patients' rehabilitation is to maintain the gained motor abilities in terms of functional independence. This could be partially obtained by applying new emerging and cutting-edge virtual/augmented reality and serious game technologies for a playful, noninvasive treatment that was demonstrated to be quite efficient and effective in enhancing the clinical status of patients and their (re)integration into society. Recently, Cloud computing and Internet of Things (IoT) emerged as technologies that can potentially revolutionize patients' care. To achieve such a goal, a system that on one hand gathers patients' clinical parameters through a network of medical IoT devices equipped with sensors and that, on the other hand, sends the collected data to a hospital Cloud for processing and analytics is required. In this paper, we assess the effectiveness of a Nintendo Wii Fit® Plus Balance Board (WFBB) used as an IoT medical device adopted in a rehabilitation training program aimed at improving the physical abilities of MS patients (pwMS). In particular, the main scientific contribution of this paper is twofold: (i) to present a preliminary new pilot study investigating whether exercises based on the Nintendo Wii Fit® balance board included in a rehabilitation training program could improve physical abilities and Quality of Life (QoL) of patients compared to that of a conventional four-week rehabilitation training program; (ii) to discuss how such a rehabilitation training program could be adopted in the perspective of near future networks of medical IoT-based rehabilitation devices, interconnected with a hospital Cloud system for big data processing to improve patients' therapies and support the scientific research about motor rehabilitation. Results demonstrate the advantages of our approach from both health and technological points of view.

Ischemic stroke and reperfusion therapies in diabetic patients.

INTRODUCTION: The study aimed to identify the main prognostic factors in diabetic patients with ischemic stroke undergoing reperfusion therapies (RT). METHODS: This retrospective study included 170 diabetic patients: 62 treated with intravenous thrombolysis (IVT) alone and 108 with mechanical thrombectomy (MT). Among MT patients, 29 underwent IVT. We collected clinical, laboratory, and radiological data. The outcomes were 3-month functional impairment (measured by modified Rankin scale, mRs), discharge neurological severity (measured by National Institutes of Health Stroke Scale score, NIHSS), 3-month mortality, intracranial hemorrhage (ICH), and symptomatic intracranial hemorrhage (SICH). We performed a general analysis for all RT and sub-group analyses for IVT and MT. RESULTS: A lower mRs was associated with lower glycemia and admission NIHSS (aNIHSS) in all RT and MT; lower aNIHSS and younger age in IVT. Mortality increased with hyperglycemia, aNIHSS, and age in all RT; age and aNIHSS in IVT; hyperglycemia and systolic pressure in MT. A lower discharge NIHSS was related with lower aNIHSS, thrombolysis, and no thrombectomy in all RT; lower aNIHSS in IVT; lower aNIHSS and thrombolysis in MT. ICH was associated with elevated aNIHSS, older age, and lower platelets in all RT; lower platelets and older age in IVT; higher aNIHSS in MT. SICH depended on longer thrombectomy duration in all RT; no metformin use in IVT; higher weight in MT. CONCLUSION: The study shed light on diabetic patients and stroke RT highlighting the protective effect of metformin in IVT and the role of glycemia, weight, and combined treatment in MT.

Repeated reperfusion treatment in recurrent ischemic stroke: A retrospective single-center case series.

Data regarding repeated reperfusion therapy (rRT) in acute ischemic stroke (AIS), including intravenous thrombolysis and endovascular treatment (EVT), are quite poor. To date, there are only few case reports and five larger studies on repeated EVT. We aimed to report our single-center experience and describe different clinical scenarios of recurrent AIS with emergent large vessel occlusion (LVO), for which the decision-making process could be challenging in the emergency setting. We retrospectively reviewed 765 consecutive AIS patients with LVO, who underwent reperfusion procedures at our comprehensive stroke center, from 2014 to 2020, and identified rRT patients. We identified and reviewed the medical records of eight patients (1.05%), who repeated reperfusive treatment for recurrent stroke within 30 days (early arterial reocclusion, EAR) and after 30 days (late arterial reocclusion, LAR). We assigned collected data to three clinical scenarios, each divided into EAR and LAR cases. All patients had recurrent emergent LVO in the same vessel territory previously affected, both in EAR and LAR patients. A good clinical outcome has been achieved in EAR patients (modified Rankin Score ≤ 2). Artery-to-artery embolic mechanism was more common in the EAR group, while LAR was more frequently associated with cardioembolic source. RRT appears to be an effective treatment option for recurrent LVO, and it should not be withheld in carefully selected patients. EVT should be considered, including aspiration-only and stenting procedures in patients with AIS and recurrent LVO after previous reperfusive treatments, even after a very short time.

Ischemic Stroke and Asymptomatic Pulmonary Opacities.

PURPOSE: Pulmonary opacities are described in many chest radiograph reports in stroke patients and are often asymptomatic. The aim of this study is to investigate the clinical features associated with asymptomatic pulmonary opacities (APO) and evaluate APO prognostic value in ischemic stroke. METHODS: We prospectively analyzed patients with acute ischemic stroke without pneumonia symptoms referred to our stroke center. All patients underwent a chest x-ray within 48 hours after admission. We divided patients with APO (defined as asymptomatic area of increased pulmonary attenuation) and patients without APO. Firstly, we compared clinical, laboratory, and echocardiographic parameters between groups; secondly, APO were evaluated as a possible predictor of the neurological severity at discharge and functional outcome at 90 days. RESULTS: We included 162 patients, 78 of whom had APO. On univariate analysis, we observed a significant difference between patients with APO and patients without APO in terms of neutrophils (73,56±10,10 vs 69,72±12,29; p=0,031), atrial fibrillation (AF, paroxysmal 27,4% vs 25,6%; permanent 19% vs 2,6%; p<0,002), cardioembolic etiology (37,2% vs 22,7%, p <0,033), thrombectomy (58,3% vs 42,9%, p <0,05), dysphagia/vomit (34,5% vs 14,10%, p<0,005), admission NIHSS (14,20±5,98 vs 10,29±5,82, p=0,001), discharge NIHSS (8,68±6,73 vs 5,64±6,20; p=0,003), and 90 days mRS (3,47±2,12 vs 2,31±1,93; p=0,001). On multivariate analysis, APO were significantly associated with admission NIHSS and AF. APO were a predictor of outcome on univariate analysis, but not on multivariate. CONCLUSION: APO in acute ischemic stroke are associated with AF. APO were not a predictor of neurological and functional outcome.

Vascular pattern and radiological follow up in a case of pontine warning syndrome.

Pontine warning syndrome (PWS) is a condition characterized by crescendo transient ischemic attacks due to pontine ischemia. The reported case described a 72-year-old woman who presented repetitive sudden episodes of double vision, impaired balance, slurred speech and right-sided weakness. Neurological deficits lasted a few minutes-hours and disappeared during the first seven days after onset. On the 1st day, MRI revealed acute left paramedian pontine infarction with focal swelling. Supra-aortic vessel imagining revealed bilateral internal carotid stenosis of 50%; hypoplasia of the left vertebral artery. On the 7th day, MRI showed a tissue swelling reduction, and from that day, she had no symptoms. These clinical and radiological features were suggestive of PWS. Our patient presented a particular vascular pattern that could favour symptoms fluctuation. We performed a close MRI follow up and it allowed us to observe a clinical stabilization in association with edema reduction.

Cerebral venous sinus thrombosis (CVST) associated with SARS-CoV-2 vaccines: clues for an immunopathogenesis common to CVST observed in COVID-19.

Severe acute respiratory syndrome coronavirus type 2 has been responsible for an unprecedented pandemic, and nowadays, several vaccines proved to be effective and safe, representing the only available strategy to stop the pandemic. While millions of people have safely received vaccine, rare and unusual thrombotic events have been reported and are undergoing investigations to elucidate their nature. Understanding initial trigger, underlying pathophysiology and the reasons for specific site localization of thrombotic events are a matter of debate.We here propose that rare cases of cerebral venous sinus thrombosis, a clinical event that may rapidly evolve to brain death, reported after COVID-19 vaccine, might be consequent to an immune response resulting in inflamed/damaged endothelium, an event similar to that described for cases of cerebral venous sinus thrombosis reported during COVID-19 and not necessarily related to anti-Platelets Factor 4 antibodies, as recently described. Remarkably, in the two patients presenting at our hospital with cerebral venous sinus thrombosis and evolved to brain death, proper tissue perfusion and function maintenance allowed organ donation despite extensive thrombosis in the organ donors, with favorable outcome at 6 months.Increased vigilance, close multidisciplinary collaboration, and further prospective research will help to better elucidate a very rare and still not fully understood pathophysiological event associated with vaccines for severe acute respiratory syndrome coronavirus 2.

Minor stroke with bilateral acute infarctions and combined vascular anomalies: A complex case report.

We report the case of a patient with bilateral acute ischemic lesions (AIS) in middle cerebral artery (MCA) territory associated with an extremely rare combination of anomalies of the aortic arch and the left internal carotid artery (ICA). The diagnosis deposed for bilateral minor embolic stroke of undetermined source (ESUS), inpatient with patent foramen ovale (PFO) and positive antiphospholipid (aPL) test. To our knowledge, this is the first description of a patient with this rare combination of vascular anomalies.

Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy.

BACKGROUND: National health-system hospitals of Lombardy faced a heavy burden of admissions for acute respiratory distress syndromes associated with coronavirus disease (COVID-19). Data on patients of European origin affected by COVID-19 are limited. METHODS: All consecutive patients aged ≥18 years, coming from North-East of Milan's province and admitted at San Raffaele Hospital with COVID-19, between February 25th and March 24th, were reported, all patients were followed for at least one month. Clinical and radiological features at admission and predictors of clinical outcomes were evaluated. RESULTS: Of the 500 patients admitted to the Emergency Unit, 410 patients were hospitalized and analyzed: median age was 65 (IQR 56-75) years, and the majority of patients were males (72.9%). Median (IQR) days from COVID-19 symptoms onset was 8 (5-11) days. At hospital admission, fever (≥ 37.5 °C) was present in 67.5% of patients. Median oxygen saturation (SpO2) was 93% (range 60-99), with median PaO2/FiO2 ratio, 267 (IQR 184-314). Median Radiographic Assessment of Lung Edema (RALE) score was 9 (IQR 4-16). More than half of the patients (56.3%) had comorbidities, with hypertension, coronary heart disease, diabetes and chronic kidney failure being the most common. The probability of overall survival at day 28 was 66%. Multivariable analysis showed older age, coronary artery disease, cancer, low lymphocyte count and high RALE score as factors independently associated with an increased risk of mortality. CONCLUSION: In a large cohort of COVID-19 patients of European origin, main risk factors for mortality were older age, comorbidities, low lymphocyte count and high RALE.

Blockchain-Based Healthcare Workflow for Tele-Medical Laboratory in Federated Hospital IoT Clouds.

In a pandemic situation such as that we are living at the time of writing of this paper due to the Covid-19 virus, the need of tele-healthcare service becomes dramatically fundamental to reduce the movement of patients, thence reducing the risk of infection. Leveraging the recent Cloud computing and Internet of Things (IoT) technologies, this paper aims at proposing a tele-medical laboratory service where clinical exams are performed on patients directly in a hospital by technicians through IoT medical devices and results are automatically sent via the hospital Cloud to doctors of federated hospitals for validation and/or consultation. In particular, we discuss a distributed scenario where nurses, technicians and medical doctors belonging to different hospitals cooperate through their federated hospital Clouds to form a virtual health team able to carry out a healthcare workflow in secure fashion leveraging the intrinsic security features of the Blockchain technology. In particular, both public and hybrid Blockchain scenarios are discussed and assessed using the Ethereum platform.

An extra virgin olive oil-enriched diet improves maternal, placental, and cord blood parameters in GDM pregnancies.

AIMS: To address the effect of a diet enriched in extra virgin olive oil (EVOO) on maternal metabolic parameters and placental proinflammatory markers in Gestational diabetes mellitus (GDM) patients. METHODS: Pregnant women at 24-28 weeks of gestation were enrolled: 33 GDM patients which were randomly assigned or not to the EVOO-enriched group and 17 healthy controls. Metabolic parameters were determined. Peroxisome proliferator activated receptor (PPAR) γ and PPARα protein expression, expression of microRNA (miR)-130a and miR-518d (which respectively target these PPAR isoforms) and levels of proinflammatory markers were evaluated in term placentas. Matrix metalloproteinases (MMPs) activity was evaluated in term placentas and umbilical cord blood. RESULTS: GDM patients that received the EVOO-enriched diet showed reduced pregnancy weight gain (GDM-EVOO:10.3 ± 0.9, GDM:14.2 ± 1.4, P = .03) and reduced triglyceridemia (GDM-EVOO:231 ± 14, GDM:292 ± 21, P = .02) compared to the non-EVOO-enriched GDM group. In GDM placentas, the EVOO-enriched diet did not regulate PPARγ protein expression or miR-130a expression, but prevented the reduced PPARα protein expression (P = .02 vs GDM) and the increased miR-518d expression (P = .009 vs GDM). Increased proinflammatory markers (interleukin-1ß, tumour necrosis factor-α and nitric oxide overproduction) in GDM placentas were prevented by the EVOO-enriched diet (respectively P = .001, P = .001 and P = .01 vs GDM). MMPs overactivity was prevented in placenta and umbilical cord blood in the EVOO-enriched GDM group (MMP-9: respectively P = .01 and P = .001 vs GDM). CONCLUSIONS: A diet enriched in EVOO in GDM patients reduced maternal triglyceridemia and weight gain and has antiinflammatory properties in placenta and umbilical cord blood, possibly mediated by the regulation of PPAR pathways.

Isolated Insular Stroke: Clinical Presentation.

The symptoms related to insular ischemia have been the object of several studies in patients affected by stroke, although they are often accompanied by other ischemic alteration of adjacent brain structures supplied by the middle cerebral artery (MCA). The insula is vulnerable because of an ischemia due to thromboembolic vascular occlusion of the M1 MCA segment and the 2 main MCA branches (M2), mainly when they abruptly arise from the principal stem at a right angle. This topographical and anatomical peculiarity could enable an embolic formation, especially due to atrial fibrillation (AF), to occlude the transition pathway between M1 and M2, while the proximal origin of vascular supply protects the insula from ischemia due to hemodynamic factors. The aim of the study is to characterize the clinical aspects of acute ischemic strokes as a first event in the insular territory with specific attention to atypical manifestation. We have considered 233 patients with a first event stroke involving the insular territory and 13 cases of isolated insular stroke (IIS), from the stroke registry of the Policlinico "G.Martino", University of Messina, between the February 10, 2014 and the February 7, 2018. IIS patients showed CT/MRI lesions restricted to the insular region. Exclusion criteria were coexisting neurological diseases, structural brain lesions, extension to the subinsular area >50% of the total infarct volume. We identified 13 IIS patients (mean age 74 years), with an isolated symptom or a combination of typical and atypical aspects. Furthermore, we observed high frequency detection of cardiac disturbances. To our knowledge, just a few previous studies have described IIS; their incidence is still not well defined. IIS manifested with a combination of deficits including motor, somatosensory, speaking, coordination, autonomic and cognitive disturbances. After an ischemic stroke, AF manifestation could follow briefly the major event and its duration could be very short, as an autonomic dysfunction due to an insular infarction. This clinical condition requires a continuous cardiac monitoring for this dangerous occurrence.

Recurrent intracranial hemorrhage and cerebral venous sinus thrombosis: an atypical case of Neuro-Behçet's Syndrome.

We report the case of a 22-year-old man with an history of headaches, seizures, cognitive impairment associated with recurrent intracranial hemorrhage (ICH), acute ischemic stroke (AIS), worsened over the last eighteen months for a new onset of uveitis and cerebral venous sinus thrombosis (CVST). After excluding common causes of lobar ICH, and some rare ones according to the diagnostic protocol proposed by Beuker et al, in the suspicion of Primary Angiitis of the Central Nervous System (PACNS), the gradual development of a low-grade fever, a cutaneous rash, and a papulopustular manifestation on lower back after rachicentesis (pathergy phenomenon), allowed us to make a diagnosis of Neuro-Behçet's Syndrome (NBS) without oral/genital aphthous ulcerations, according to the International Study Group for Behçet's Disease classification criteria for BD (ICBD).

Hemiballism: Unusual clinical manifestation in three patients with frontoparietal infarct.

The term hemiballism-hemichorea refers to a movement disorder characterized by involuntary movements, often violent, described as uncontrollable jerking, flinging, flailing or kicking, involving proximal muscles of a limb and it is often associated with lesions in the subthalamic nucleus. In this report, we described three cases of hemiballism-hemichorea as the first manifestation of acute ischemic stroke with lesion in the frontoparietal region on brain MRI and no involvement of the subthalamic nucleus. One patient was treated with thrombolysis and recovered within one hour. The other patients recovered within 48 h from symptoms onset. The impairment of the recently described "hyperdirect way", in which the cortical signal reach directly the subthalamic nucleus, may underlie the symptoms. We support, with a clinical point of view, the role of the frontoparietal region in the genesis of the hemiballism-hemichorea. An acute onset of this symptom should lead to think to an acute stroke.

Multidisciplinary management of the nocebo effect in biosimilar-treated IBD patients: Results of a workshop from the NOCE-BIO consensus group.

The high cost of biological drugs for patients with inflammatory bowel disease (IBD) considerably impacts on health-care budgets. Since the patent of biological products expired, cheaper biosimilars have entered the market. Available data coming from real-world cohorts and clinical trials indicate that the efficacy and safety of biosimilars is comparable to that of the originator drugs. Treating IBD patients with a biosimilar may be complicated by the risk of the nocebo effect, a negative effect of a pharmacological or non-pharmacological treatment, induced by patients's expectations and unrelated to the physiological action of the treatment. The nocebo effect can negatively affect treatment outcomes and hamper the cost-savings of biosimilars. Reducing the nocebo effect requires a multidisciplinary effort of all health-care providers in charge of biosimilar-treated IBD patients. The aim of the review is to reflect the key messages of an international workshop on this topic, including viewpoints from the perspective of physicians, nurses, psychologists, pharmacists and patients.