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Finding reliable parameters to identify patients with heart failure (HF) that will respond to cardiac resynchronization therapy (CRT) represents a major challenge. We and others have observed post-translational modifications of Ryanodine Receptor (RyR) in several tissues (including skeletal muscle and circulating lymphocytes) of patients with advanced HF. We designed a prospective study to test the hypothesis that RyR1 glycation in circulating lymphocytes could predict CRT responsiveness in patients with non-ischemic HF. We enrolled 94 patients who underwent CRT and 30 individuals without HF, examining RyR1 glycation in peripheral lymphocytes at enrollment and after 1 year. We found that baseline RyR1 glycation independently predicts CRT response at 1 year after adjusting for age, diabetes, QRS duration and morphology, echocardiographic dyssynchrony, and hypertension. Moreover, RyR1 glycation in circulating lymphocytes significantly correlated with pathologic intracellular calcium leak. Taken together, our data show for the first time that RyR1 glycation in circulating lymphocytes represents a novel biomarker to predict CRT responsiveness.

Background and objectives: To explore cognitive, EEG, and MRI features in COVID-19 survivors up to 10months after hospital discharge. Methods: Adult patients with a recent diagnosis of COVID-19 and reporting subsequent cognitive complaints underwent neuropsychological assessment and 19-channel-EEG within 2months (baseline, N = 49) and 10months (follow-up, N = 33) after hospital discharge. A brain MRI was obtained for 36 patients at baseline. Matched healthy controls were included. Using eLORETA, EEG regional current densities and linear lagged connectivity values were estimated. Total brain and white matter hyperintensities (WMH) volumes were measured. Clinical and instrumental data were evaluated between patients and controls at baseline, and within patient whole group and with/without dysgeusia/hyposmia subgroups over time. Correlations among findings at each timepoint were computed. Results: At baseline, 53% and 28% of patients showed cognitive and psychopathological disturbances, respectively, with executive dysfunctions correlating with acute-phase respiratory distress. Compared to healthy controls, patients also showed higher regional current density and connectivity at delta band, correlating with executive performances, and greater WMH load, correlating with verbal memory deficits. A reduction of cognitive impairment and delta band EEG connectivity were observed over time, while psychopathological symptoms persisted. Patients with acute dysgeusia/hyposmia showed lower improvement at memory tests than those without. Lower EEG delta band at baseline predicted worse cognitive functioning at follow-up. Discussion: COVID-19 patients showed interrelated cognitive, EEG, and MRI abnormalities 2months after hospital discharge. Cognitive and EEG findings improved at 10months. Dysgeusia and hyposmia during acute COVID-19 were related with increased vulnerability in memory functions over time.

To assess if the amplitude of the N20 wave (N20Amp) of somatosensory evoked potentials (SSEPs) changes between 12-24 h and 72 h from the return of spontaneous circulation (ROSC) after cardiac arrest and if an N20Amp decrease predicts poor neurological outcome (CPC 3-5) at six months.Retrospective analysis of the ProNeCA multicentre prognostication study dataset. (NCT03849911).In adult comatose cardiac arrest survivors whose SSEPs were recorded at both 12-24 h and 72 h after ROSC, we measured the median N20Amp at each timepoint and the individual change in N20Amp across the two timepoints. We identified their cutoffs for predicting poor outcome with 0% false positive rate (FPR) and compared their sensitivities.We included 236 patients. The median [IQR] N20Amp increased from 1.90 [0.78-4.22] µV to 2.86 [1.52-5.10] µV between 12-24 h and 72 h (p = 0.0019). The N20Amp cutoff for 0% FPR increased from 0.6 µV at 12-24 h to 1.23 µV at 72 h, and its sensitivity increased from 56[48-64]% to 71[63-77]%. Between 12-24 h and 72 h, an N20Amp decrease 53% predicted poor outcome with 0[0-5]% FPR and 26[19-35]% sensitivity. Its combination with an N20Amp 1.23 µV at 72 h increased sensitivity by 1% to 72[64-79]%.In comatose cardiac arrest survivors, the median N20Amp and its cutoff for predicting poor neurological outcome increase between 12-24 and 72 h after ROSC. An N20Amp decrease greater than 53% between these two timepoints predicts poor outcome with 0% FPR, confirming the unfavourable prognostic signal of a low N20Amp at 72 h.

BACKGROUND: To the best of our knowledge, the association of physical impairment and cognitive decline has never been investigated in frail patients with acute myocardial infarction. AIM: The aim of our study is to assess the correlation between physical and cognitive dysfunction in frail patients with ST-elevation myocardial infarction (STEMI). METHODS: We examined consecutive frail patients with first STEMI treated with primary percutaneous coronary intervention (PPCI). All patients were evaluated via Mini Mental State Examination (MMSE) and 5-m gait speed test after PPCI. RESULTS: A total of 871 frail patients with suspected STEMI were admitted and 301 patients successfully completed the study. We found that the gait speed significantly correlated with the MMSE score (r: 0.771; p: < 0.001). The independent effects on MMSE score were confirmed in a linear multivariate analysis. CONCLUSIONS: Taken together, our findings indicate that an assessment of both cognitive and physical conditions should be included in the comprehensive geriatric evaluation of hospitalized older STEMI patients.

Primary percutaneous coronary intervention (PPCI) is a pivotal treatment in ST-segment elevation myocardial infarction (STEMI) patients. However, in hyperglycemic-STEMI patients, the incidence of death is still significant. Here, the involvement of sirtuin 1 (SIRT1) and miR33 on the pro-inflammatory/pro-coagulable state of the coronary thrombus was investigated. Moreover, 1-year outcomes in hyperglycemic STEMI in patients subjected to thrombus aspiration before PPCI were evaluated. Results showed that hyperglycemic thrombi displayed higher size and increased miR33, reactive oxygen species, and pro-inflammatory/pro-coagulable markers. Conversely, the hyperglycemic thrombi showed a lower endothelial SIRT1 expression. Moreover, in vitro experiments on endothelial cells showed a causal effect of SIRT1 modulation on the pro-inflammatory/pro-coagulative state via hyperglycemia-induced miR33 expression. Finally, SIRT1 expression negatively correlated with STEMI outcomes. These observations demonstrate the involvement of the miR33/SIRT1 pathway in the increased pro-inflammatory and pro-coagulable state of coronary thrombi in hyperglycemic STEMI patients.

Objective We evaluated sodium-glucose co-transporter2 (SGLT2) expression and the effect of SGLT2 inhibitor (SGLT2i) therapies on carotid plaques of asymptomatic diabetic and non-diabetic patients. Methods Plaques were obtained from 296 non-diabetic patients and 227 patients with type 2 diabetes undergoing carotid endarterectomy. 97 patients with type 2 diabetes were treated with SGLT2 inhibitors for 16 ± 4 months before endarterectomy. After propensity score matching analysis, patients with type 2 diabetes were categorized without (n = 87) and with SGLT2i therapy (n = 87). To investigate SGLT2 expression levels' effects on major adverse endpoints (MACE = stroke, transient ischemic attack, myocardial infarction, and death), we evaluated MACE outcomes at a 2-year follow-up. Results Compared to plaques from patients without diabetes, plaques from patients with diabetes had higher SGLT2 expression, inflammation, and oxidative stress, along with lower SIRT6 expression and collagen content. Compared with plaques from patients with diabetes, SGLT2i-treated patients with type 2 diabetes presented increased SIRT6 expression and collagen content and lowered inflammation and ion and oxidative stress, thus indicating a more stable plaque phenotype. These results supported in vitro observations on human aorta endothelial cells (EC) (TeloHAEC-cells). Indeed, EC treated with high glucose (25 mM) in the presence of SGLT2i (100 nM canagliflozin) presented higher SIRT6 expression and decreased mRNA and protein SGLT2 levels, nuclear factor-kappa B (NF-B(NF-κB), and matrix metallopeptidase 9 (MMP-9) expression compared to cells treated only with high glucose. After two years following endarterectomy, a multivariable Cox regression analysis showed significantly higher 2-year overall survival from MACE in patients without diabetes (P, Highlights • The identification of novel molecular targets of atherosclerosis progression is of utmost importance in diabetic patients. • The occurrence of SGLT2 receptors on the endothelial cells of atherosclerotic plaques may be an attractive therapeutic option for atherosclerosis in patients with diabetes. • SGLT2/SIRT6 represents an attractive option, given its crucial involvement in atherosclerosis progression. • The endothelial SGLT2 inhibition increases the endothelial expression of SIRT6, yielding an improved atherosclerotic plaque phenotype and 2-year outcome. • The impairment of the endothelial SGLT2/SIRT6 pathway worsens outcomes in atherosclerotic patients with diabetes; this may be a potential preventive target.

Background. The viral load of asymptomatic SAR-COV-2 positive (ASAP) persons have been equal to that of symptomatic patients, suggesting a similar risk for endothelial dysfunction and increased coagulation in asymptomatic and symptomatic patients. To date, there are no reports of ST-elevation myocardial infarction (STEMI) outcomes in ASAP patients. We evaluated thrombus burden and thrombus viral load and their impact on microvascular bed perfusion in the infarct area (myocardial lush grade, MBG) in ASAP compared to SARS-COV-2 negative (SANE) STEMI patients. Methods. This was an observational study of 46 ASAP, and 130 SANE patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention and thrombus aspiration. The primary endpoints were thrombus dimension + thrombus viral load effects on MBG after PPCI. The secondary endpoints during hospitalization were major adverse cardiovascular events (MACEs). MACEs are defined as a composite of cardiovascular death, nonfatal acute AMI, and heart failure during hospitalization.Results. Thrombus dimensions were significantly higher in ASAP patients as compared to SANE patients. Interestingly, 39 (84.9%) of ASAP patients also had thrombus specimens positive for SARS-COV-2. In ASAP STEMI patients (n=46), thrombus viral load was a significant determinant of thrombus dimension independently of risk factors (pConclusions. In ASAP patients presenting with STEMI, there is strong evidence towards higher thrombus viral load, dimension, and poorer MBG. These data support the need to reconsider ASAP status as a risk factor that may worsen STEMI outcomes.

ST-elevation myocardial infarction (STEMI) is one of the leading causes of death and hospitalization worldwide (1). Hyperglycemia (HG) has been shown to adversely affect STEMI clinical outcomes, leading to higher mortality and severe complications (1,2). The aim of our study was to investigate the impact of HG at hospital admission on the risk of restenosis after primary percutaneous coronary intervention (PCI) for STEMI, comparing normoglycemic subjects (NG group), patients without diabetes mellitus (DM) but with HG (HG-non-DM group), and patients with both HG and DM (HG-DM group). HG was defined by glycemia >140 mg/dL, according to the guidelines of the American Diabetes Association (3). We evaluated STEMI patients referred to the Division of Cardiology of “Antonio Cardarelli” Hospital from February 2008 to February 2016. Inclusion criteria were age >18 years and first STEMI. Exclusion criteria were left ventricular ejection fraction

Background Despite primary percutaneous coronary intervention (PPCI) is generally considered the best therapy in older frail adults with ST-segment elevation myocardial infarction (STEMI), the incidence of re-hospitalization for cardiovascular diseases remains significant in these patients. Aims We hypothesized that thrombus aspiration (TA) before PPCI could be a useful treatment for reducing mortality and rehospitalizations in frail patients undergoing PPCI for STEMI. Methods We conducted a study comparing PPCI alone vs TA + PPCI in frail STEMI patients. We examined a cohort of consecutive frail patients aged ≥ 65 years with first STEMI treated with PPCI between February 2008 and July 2015 at the Department of Cardiology of the “Cardarelli” Hospital in Naples, Italy. Results The study was completed by 389 patients (PPCI: 195, TA + PPCI: 194). At 1-month follow-up, the rate of death from any cause was 7.0% in patients treated with PPCI alone vs 3.0% in patients treated with TA + PPCI (p 0.036), whereas death from cardiovascular causes was 6.0% in the PPCI group vs 3.0% in the TA + PPCI group (p 0.028). Equally important, the rate of re-hospitalization due to heart failure was 7.5% in the PPCI group vs 4.0% in TA + PPCI group (p 0.025) and the rate of re-hospitalization due to acute coronary syndrome was 10.0% in the PPCI group vs 4.5% in the TA + PPCI group (p 0.016). Conclusion These results indicate the importance of TA in the treatment of STEMI in a group of high-risk patients such as elderly with frailty.

Highlights • Theta density increase is the earliest and most sensitive EEG marker of AD pathology. • Alpha2 density progressively decreases following the progression of AD pathology. • EEG graph analysis of ADD patients shows network derangement at theta and alpha2 band. • EEG/fMRI integration model empowered EEG diagnostic performances., Objective We evaluated the value of resting-state EEG source biomarkers to characterize mild cognitive impairment (MCI) subjects with an Alzheimer’s disease (AD)-like cerebrospinal fluid (CSF) profile and to track neurodegeneration throughout the AD continuum. We further applied a resting-state functional MRI (fMRI)-driven model of source reconstruction and tested its advantage in terms of AD diagnostic accuracy. Methods Thirty-nine consecutive patients with AD dementia (ADD), 86 amnestic MCI, and 33 healthy subjects enter the EEG study. All ADD subjects, 37 out of 86 MCI patients and a distinct group of 53 healthy controls further entered the fMRI study. MCI subjects were divided according to the CSF phosphorylated tau/β amyloid-42 ratio (MCIpos: ≥ 0.13, MCIneg: < 0.13). Using Exact low-resolution brain electromagnetic tomography (eLORETA), EEG lobar current densities were estimated at fixed frequencies and analyzed. To combine the two imaging techniques, networks mostly affected by AD pathology were identified using Independent Component Analysis applied to fMRI data of ADD subjects. Current density EEG analysis within ICA-based networks at selected frequency bands was performed. Afterwards, graph analysis was applied to EEG and fMRI data at ICA-based network level. Results ADD patients showed a widespread slowing of spectral density. At a lobar level, MCIpos subjects showed a widespread higher theta density than MCIneg and healthy subjects; a lower beta2 density than healthy subjects was also found in parietal and occipital lobes. Evaluating EEG sources within the ICA-based networks, alpha2 band distinguished MCIpos from MCIneg, ADD and healthy subjects with good accuracy. Graph analysis on EEG data showed an alteration of connectome configuration at theta frequency in ADD and MCIpos patients and a progressive disruption of connectivity at alpha2 frequency throughout the AD continuum. Conclusions Theta frequency is the earliest and most sensitive EEG marker of AD pathology. Furthermore, EEG/fMRI integration highlighted the role of alpha2 band as potential neurodegeneration biomarker.

Objectives: We examined the association of the coronary thrombus microbiota and relative metabolites with major adverse cardiovascular events (MACE) in hyperglycemic patients with ST segment elevation myocardial infarction (STEMI). Background: Hyperglycemia during STEMI may affect both development and progression of coronary thrombus via gut and thrombus microbiota modifications. Methods: We undertook an observational cohort study of 146 first STEMI patients treated with primary percutaneous coronary intervention (PPCI) and thrombus-aspiration (TA). Patients were clustered, based on admission blood glucose levels, in hyperglycemic (≥140 mg/dl) and normoglycemic (

Aim To assess if, in comatose resuscitated patients, the amplitude of the N20 wave (N20amp) of somatosensory evoked potentials (SSEP) can predict 6-months neurological outcome. Setting Multicentre study in 13 Italian intensive care units. Methods The N20amp in microvolts (μV) was measured at 12 h, 24 h, and 72 h from cardiac arrest, along with pupillary reflex (PLR) and a 30-min EEG classified according to the ACNS terminology. Sensitivity and false positive rate (FPR) of N20amp alone or in combination were calculated. Results 403 patients (age 69[58–68] years) were included. At 12 h, an N20amp >3 μV predicted good neurological outcome (Cerebral Performance Categories [CPC] 1–2) with 61[50−72]% sensitivity and 11[6–18]% FPR. Combining it with a benign (continuous or nearly continuous) EEG increased sensitivity to 91[82−96]%. For poor outcome (CPC 3–5), an N20Amp ≤0.38 μV, ≤0.73 μV and ≤1.01 μV at 12 h, 24 h, and 72 h, respectively, had 0% FPR with sensitivity ranging from 61[51−69]% and 82[76−88]%. Sensitivity was higher than that of a bilaterally absent N20 at all time points. At 12 h and 24 h, a highly malignant (suppression or burst-suppression) EEG and bilaterally absent PLR achieved 0% FPR only when combined with SSEP. A combination of all three predictors yielded a 0[0−4]% FPR, with maximum sensitivity of 44[36−53]%. Conclusion At 12 h from arrest, a high N20Amp predicts good outcome with high sensitivity, especially when combined with benign EEG. At 12 h and 24 h from arrest a low-voltage N20amp has a high sensitivity and is more specific than EEG or PLR for predicting poor outcome.

Objective This research was focused on expert professionals in epilepsy care to understand their points of view on the care pathway and their living relationships with patients. Methods Researchers prepared a semi-structured parallel chart and distributed it online among 21 Italian centres of care. Each health professional was prompted to write five narratives on cases of patients with epilepsy, subsequently analysed through narrative medicine methods. Next, a consensus meeting was held, to individualise an action plan based on the narratives. Results Ninety-one parallel charts were collected from 25 epileptologists, who had a mean age of 50 years; their narratives concerned patients with a mean age of 37 years, with different types of epilepsy (53 % drug-resistant; 31 % unemployed). The limitations in the daily life of people with epilepsy (57 %), employment (42 %), caregiver burden (51 %), and the universal prevalence of fear were the primary topics that emerged. Attentive and reassuring care relationships were found to be the main element of coping (21 %). A new multi-factorial classification of epilepsies, integrating clinical with social and legal risk factors, was the main agreed action to face the issues identified. Conclusions The narrative medicine approach supplied a broader scenario of living with epilepsy, including the family and social impact and possible effects on the choices for care pathways. The epileptologists showed a strong motivation to care for patients with epilepsy and deep involvement in the care relationships; the use of parallel chart demonstrated to be an effective tool to preserve their wellbeing.

Delirium is classically defined as an acute, transient, global, organic disturbance of cognitive functions that leads to loss of attention and fluctuating impairment of consciousness.

The purpose of the following chapter is to define a diagnostic and therapeutic pathway for epileptic seizures in the setting of emergency care. Therefore, only aspects related to the initial stage of care for patients with probable or suspected recent-onset epileptic seizures will be extensively discussed.

Objectives. We examined the association of the coronary thrombus microbiota and relative metabolites with major adverse cardiovascular events (MACE) in hyperglycemic patients with ST segment elevation myocardial infarction (STEMI).Background. Hyperglycemia during STEMI may affect both development and progression of coronary thrombus via gut and thrombus microbiota modifications. Methods. We undertook an observational cohort study of 146 first STEMI patients treated with primary percutaneous coronary intervention (PPCI) and thrombus-aspiration (TA). Patients were clustered, based on admission blood glucose levels, in hyperglycemic (>140 mg/dl) and normoglycemic (Prevotellaspp and TMAO terziles and MACE. MACE endpoint at 1 year included death, re-infarction, unstable angina.Results. In fecal and thrombus samples, we observed a significantly different prevalence of both Prevotellaspp and Alistipesspp. between patients with hyperglycemia (n=56) and those with normal glucose levels (n=90). The abundance of Prevotella increased in hyperglycemic vs normoglycemic patients whereas the contrary was observed for Alistipes. Interestingly, in coronary thrombus, the content of Prevotella was associated with admission blood glucose levels (pPrevotella and TMAO in coronary thrombus as compared to patients with low levels of Prevotella and TMAO, after 1-year follow up.Conclusions. Hyperglycemia during STEMI may increase coronary thrombus burden via gut and thrombus microbiota dysbiosis characterized by an increase of Prevotella and TMAO content in thrombi.

BACKGROUND : Admission hyperglycemia is common in subjects with acute myocardial infarction (AMI). Reperfusion therapy with primary percutaneous coronary intervention (PPCI) represents the leading therapeutic choice, in particular in ST-segment elevation myocardial infarction (STEMI). Despite this, mortality, re-hospitalizations and complications remain a relevant problem. Adenosine, a purine nucleoside, may reduce no-reflow. Therefore, we studied the effects of intravenous infusion of adenosine in addition to primary percutaneous coronary intervention (PPCI) in hyperglycemic patients with STEMI. METHODS : We evaluated 836 patients with STEMI and admission hyperglycemia (glycemia > 140 mg/dL). At the end, 399 patients were entered into the database. Patients were grouped on the basis of whether they received adenosine or not. RESULTS : A total of 199 patients received intravenous adenosine infusion and PPCI and 200 patients did not. Kaplan–Meier analysis demonstrated significant differences in all death, cardiac death, re-hospitalization for heart failure and for acute coronary syndrome in the adenosine treated group. CONCLUSIONS : The effects of intravenous infusion of adenosine and PPCI on clinical outcomes are significant but we need future larger studies with larger follow-up and statistical analysis to confirm our results.

OBJECTIVE To evaluate the effect of metformin therapy on coronary endothelial function and major adverse cardiac events (MACE) in patients with prediabetes with stable angina and nonobstructive coronary stenosis (NOCS). RESEARCH DESIGN AND METHODS Metformin therapy may be needed to reduce coronary heart disease risk in patients with prediabetes. A total of 258 propensity score–matched (PSM) patients with stable angina undergoing coronary angiography were enrolled in the study. Data from 86 PSM subjects with normoglycemia (NG), 86 PSM subjects with prediabetes (pre-DM), and 86 PSM subjects with prediabetes treated with metformin (pre-DM metformin) were analyzed. During coronary angiography, NOCS was categorized by luminal stenosis 0.80. In addition, we assessed the endothelial function, measuring coronary artery diameter of left anterior descending coronary (LAD) at baseline and after the infusion of acetylcholine, by means of an intracoronary Doppler guide wire. MACE, as cardiac death, myocardial infarction, and heart failure, was evaluated at 24 months of follow-up. RESULTS At baseline, NG patients had a lower percentage of LAD endothelial dysfunction compared with pre-DM patients (P < 0.05). The pre-DM patients had a higher percentage of endothelial LAD dysfunction as compared with the pre-DM metformin patients (P < 0.05). At the 24th month of follow-up, MACE was higher in pre-DM versus NG (P < 0.05). In pre-DM metformin patients, MACE was lower compared with pre-DM patients (P < 0.05). CONCLUSIONS Metformin therapy may reduce the high risk of cardiovascular events in pre-DM patients by reducing coronary endothelial dysfunction.

Bilateral absence of N20 peak in median nerve Somatosensory Evoked Potentials (SSEPs) is considered the most valid predictor of poor outcome in comatose survivors after cardiopulmonary resuscitation. We investigated the consistency in interpreting SSEP recordings in a multicentre study.44 SSEP recordings randomly extracted from 600 recordings of 392 patients included in the "Prognostication of Neurological outcome after Cardiac Arrest (ProNeCa) study" were blindly read by three expert neurophysiologists. Agreement between raters, and individual agreement of each rater vs. reference standard (RS), were calculated using Kappa Coefficients. Inter-rater reliability was calculated with Intra-class Correlation Coefficient (ICC).When raters had to evaluate the presence of N20 with normal amplitude, the inter-rater agreement was very high (Kappa = 0.84). In the case of N20 absence the agreement was good (Kappa = 0.66), but when N20 amplitude was low, the agreement decreased to moderate (Kappa = 0.579) becoming even weaker when it was "Non Assessable" (Kappa = 0.107). The agreement of each rater with the RS had a range from moderate to very good; rater1 Kappa = 0.589 (95%CI 0.397-0.781; p 0.001), rater2 Kappa = 0.644 (95%CI 0.460-0.828; p 0.001), rater3 Kappa = 0.859 (95%CI 0.698-1.000; p 0.001). The ICC was barely good, 0.682 (95%CI 0.539-0.798; p = 0.0075).Different health professionals, using different equipment in a multicentre study, had very good inter-rater agreement in interpreting SSEP records. The interpretation of "Non Assessable" SEPPs, mainly in relation to noise level, is still a crucial issue because it increases rater uncertainty. For this reason, it is important to focus on improving recording quality and interpretation of records.

Aims To assess the accuracy of electroencephalogram (EEG) and somatosensory evoked potentials (SEPs) recorded at 12 and 72 h from resuscitation for predicting six-months neurological outcome in patients who are comatose after cardiac arrest. Methods Prospective multicentre prognostication study. EEG was classified according to the American Clinical Neurophysiology Society terminology. SEPs were graded according to the presence and amplitude of their cortical responses. Neurological outcome was defined as good (cerebral performance categories [CPC] 1–3) vs. poor (CPC 4–5). None of the patients underwent withdrawal of life-sustaining treatment. Results A total of 351 patients were included, of whom 134 (38%) had good neurological outcome. At 12 h, a continuous, nearly continuous and low-voltage EEG pattern predicted good neurological outcome with 71[61–80]% sensitivity, while an isoelectric EEG and a bilaterally absent/absent-pathological amplitude (AA/AP) cortical SEP pattern predicted poor neurological outcome with 14[8–21]% and 59[50–68]% sensitivity, respectively. Specificity was 100[97–100]% for all predictors. At 72 h, both an isoelectric, suppression or burst-suppression pattern on EEG and an AA/AP SEP pattern predicted poor outcome with 100[97–100]% specificity. Their sensitivities were 63[55–70]% and 66[58–74]%, respectively. When EEG and SEPs were combined, sensitivity for poor outcome prediction increased to 79%. Conclusions In comatose resuscitated patients, EEG and SEPs predicted good and poor neurological outcome respectively, with 100% specificity as early as 12 h after cardiac arrest. At 72 h after arrest, unfavourable EEG and SEP patterns predicted poor neurological outcome with 100% specificity and high sensitivity, which further increased after their combination.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a potentially fatal autoimmune disease, characterized by autoantibody-mediated neurotransmission impairment in multiple brain locations. The course of this condition often comprises altered mental status, autonomic dysfunctions, refractory seizures and hyperkinetic movement disorders. Available disease-modifying therapies include corticosteroids, i.v. immunoglobulins, plasma exchange, rituximab and cyclophosphamide. In a subgroup of patients not responding to B-cell depletion, bortezomib, a proteasome inhibitor, has shown promising evidence of efficacy. The time course of recovery from acute phase may be very slow (weeks/months), and only few data are available in literature about the concurrent management of encephalitis-associated movement disorders. We report a case of severe anti-NMDAR encephalitis in a 29-year-old woman, not responsive to first- and second-line treatments, with persistent involuntary motor manifestations. Starting three months after symptom onset, four cycles of bortezomib have been administered; subsequently we observed a progressive improvement of neurological status. Meanwhile, motor manifestations were controlled after the administration of tramadol, a non-competitive NMDA receptor antagonist.

Since the publication of the Italian League Against Epilepsy guidelines for the treatment of status epilepticus in 2006, advances in the field have ushered in improvements in the therapeutic arsenal. The present position paper provides neurologists, epileptologists, neurointensive care specialists, and emergency physicians with updated recommendations for the treatment of adult patients with status epilepticus. The aim is to standardize treatment recommendations in the care of this patient population.

Early recognition and treatment of autoimmune encephalitis (AE) are crucial for patients, but diagnosis is often difficult and time-consuming. For this purpose, a syndrome-based diagnostic approach was published by Graus et al. (Lancet Neurol 15:391–404, 2016), but very little is known in the literature about its application in clinical practice. Our aims are to test the feasibility of such approach in a real-world single-centre setting and to analyse the most relevant factors in criteria fulfilment. We retrospectively applied these criteria to our cohort of patients discharged from our hospital with diagnosis of autoimmune encephalitis (n = 33, 58% antibody-positive). All the subjects fulfilled criteria for possible AE (pAE), with EEG and MRI playing a central role in diagnosis, while CSF was useful mainly to rule out other conditions. Three patients respected criteria for probable anti-NMDA-R encephalitis (pNMDA). Definite anti-NMDAR encephalitis was diagnosed in 4 patients with detection of the autoantibody but, surprisingly, none of these subjects had fulfilled criteria for pNMDA. 18 patients were diagnosed with definite limbic AE (15 patients were antibody-positive, three antibody-negative). Need for MRI bilateral involvement in antibody-negative limbic AE limited diagnosis. One patient fulfilled criteria for probable antibody-negative AE, while ten patients remained classified as pAE. From our retrospective analysis, some suggestions for a better definition of the criteria may emerge. Larger studies on prospective cohorts may be more helpful to explore possible important issues.

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In electroencephalography books, relative significance is given to “status epilepticus” (SE), maybe because of the idea that it could only be a simple repetition of seizures in a very short time from one another. Actually, at least two factors contribute making the EEG patterns of SE much more complex: the first is the overlapping of the transients related to the seizures with those related to underlying disease, and the second is the EEG modification related to a sustained or prolonged status epilepticus. The EEG of the SE can thus follow its graphic expression which is different from that of single seizures repeated over time, coming up to express critical patterns that are not always easily recognizable. The elements of pathophysiology and clinical electroencephalographic practice show that the SE is a dynamic pathological process that expresses itself in a different manner from patient to patient depending on its etiology, duration, topographic extension, clinical manifestation, and therapeutic interventions that are carried out. The proposed classification of SE in 2015 (Trinka et al., Epilepsia 56(10):1515–23, 2015) establishes the importance of EEG in the diagnosis and management of the SE by including the EEG axial description to define a correct classification of the patient.

Summary Objective Although many studies have attempted to describe treatment outcomes in patients with drug‐resistant epilepsy, results are often limited by the adoption of nonhomogeneous criteria and different definitions of seizure freedom. We sought to evaluate treatment outcomes with a newly administered antiepileptic drug (AED) in a large population of adults with drug‐resistant focal epilepsy according to the International League Against Epilepsy (ILAE) outcome criteria. Methods This is a multicenter, observational, prospective study of 1053 patients with focal epilepsy diagnosed as drug‐resistant by the investigators. Patients were assessed at baseline and 6, 12, and 18 months, for up to a maximum of 34 months after introducing another AED into their treatment regimen. Drug resistance status and treatment outcomes were rated according to ILAE criteria by the investigators and by at least two independent members of an external expert panel (EP). Results A seizure‐free outcome after a newly administered AED according to ILAE criteria ranged from 11.8% after two failed drugs to 2.6% for more than six failures. Significantly fewer patients were rated by the EP as having a “treatment failure” as compared to the judgment of the investigator (46.7% vs 62.9%, P

We evaluate whether the thrombus aspiration (TA) before primary percutaneous coronary intervention (PPCI) may improve STEMI outcomes in hyperglycemic patients.The management of hyperglycemic patients during STEMI is unclear.We undertook an observational cohort study of 3166 first STEMI. Patients were grouped on the basis of whether they received TA or not. Moreover, among these patients we selected a subgroup of STEMI patients with hyperglycemia during the event (glycaemia 140 mg/dl). The endpoint at 1 year included all-cause mortality, cardiac mortality and re-hospitalization for coronary disease, heart failure and stroke.One-thousand STEMI patients undergoing PPCI to plus TA (TA-group) and 1504 STEMI patients treated with PPCI alone (no-TA group) completed the study. In overall study-population, Kaplan-Meier-analysis demonstrated no significant difference in mortality rates between patients with and without TA (P = 0.065). After multivariate Cox-analysis (HR: 0.94, 95% CI 0.641-1.383) and the addition of propensity matching (HR: 0.86 95% CI 0.412-1.798) TA was still not associated with decreased mortality. By contrast, in hyperglycemic subgroup STEMI patients (TA-group, n = 331; no-TA group, n = 566), Kaplan-Meier-analysis demonstrated a significantly lower mortality (P = 0.019) in TA-group than the no-TA group. After multivariate Cox-analysis (HR: 0.64, 95% CI 0.379-0.963) and the addition of propensity matching (HR: 0.54, 95% CI 0.294-0.984) TA was still associated with decreased mortality.TA was not associated with lower mortality in PPCI for STEMI when used in our large all-comer cohort. Conversely, TA during PPCI for STEMI reduces clinical outcomes in hyperglycemic patients. Trial registration NCT02817542. 25th, June 2016.

There are insufficient data on the prognosis and management of people with type 2 diabetes who experience a non-obstructive coronary artery stenosis (NOCS)-non-ST-elevation myocardial infarction (NSTEMI) event. We evaluated the 12-month prognosis of patients with diabetes and NOCS (20%-49% luminal stenosis) who experience a first NSTEMI as compared with patients without diabetes. In addition, we investigated the 12-month prognosis in patients with diabetes and NSTEMI-NOCS previously treated with incretin-based therapy compared with a matched cohort of patients with NSTEMI-NOCS never treated with such therapy. We categorized the patients with diabetes as current incretin users (6 months' treatment with glucagon-like peptide-1 agonists or dipeptidyl peptidase-4 inhibitors) and non-users of incretins. The endpoint was all-cause mortality, cardiac death, recurrent acute coronary syndrome (ACS), and heart failure. The unadjusted Kaplan-Meier analysis, and a risk-adjusted hazard analysis showed that, all-cause mortality, cardiac death, readmission for ACS and heart failure rates during the 12-month follow-up were higher in patients with diabetes and NOCS-NSTEMI than in those with NOCS-NSTEMI without diabetes. Among the patients with diabetes, the current incretin users had a significantly lower rate of all-cause mortality, cardiac death and readmission for ACS at 12 months. In patients with type 2 diabetes and NOCS-NSTEMI, we observed a higher incidence of 1-year mortality and adverse cardiovascular outcomes, as compared with patients without diabetes with NOCS-NSTEMI. In people with diabetes, non-users of incretins had a worse prognosis than current incretin users. There are insufficient data on the prognosis and management of people with type 2 diabetes who experience a non-obstructive coronary artery stenosis (NOCS)-non-ST-elevation myocardial infarction (NSTEMI) event. We evaluated the 12-month prognosis of patients with diabetes and NOCS (20%-49% luminal stenosis) who experience a first NSTEMI as compared with patients without diabetes. In addition, we investigated the 12-month prognosis in patients with diabetes and NSTEMI-NOCS previously treated with incretin-based therapy compared with a matched cohort of patients with NSTEMI-NOCS never treated with such therapy. We categorized the patients with diabetes as current incretin users (6months' treatment with glucagon-like peptide-1 agonists or dipeptidyl peptidase-4 inhibitors) and non-users of incretins. The endpoint was all-cause mortality, cardiac death, recurrent acute coronary syndrome (ACS), and heart failure. The unadjusted Kaplan-Meier analysis, and a risk-adjusted hazard analysis showed that, all-cause mortality, cardiac death, readmission for ACS and heart failure rates during the 12-month follow-up were higher in patients with diabetes and NOCS-NSTEMI than in those with NOCS-NSTEMI without diabetes. Among the patients with diabetes, the current incretin users had a significantly lower rate of all-cause mortality, cardiac death and readmission for ACS at 12months. In patients with type 2 diabetes and NOCS-NSTEMI, we observed a higher incidence of 1-year mortality and adverse cardiovascular outcomes, as compared with patients without diabetes with NOCS-NSTEMI. In people with diabetes, non-users of incretins had a worse prognosis than current incretin users.

Objectives We evaluate whether the thrombus aspiration (TA) before primary percutaneous coronary intervention (PPCI) may improve STEMI outcomes in hyperglycemic patients. Background The management of hyperglycemic patients during STEMI is unclear. Methods We undertook an observational cohort study of 3166 first STEMI. Patients were grouped on the basis of whether they received TA or not. Moreover, among these patients we selected a subgroup of STEMI patients with hyperglycemia during the event (glycaemia > 140 mg/dl). The endpoint at 1 year included all-cause mortality, cardiac mortality and re-hospitalization for coronary disease, heart failure and stroke. Results One-thousand STEMI patients undergoing PPCI to plus TA (TA-group) and 1504 STEMI patients treated with PPCI alone (no-TA group) completed the study. In overall study-population, Kaplan–Meier-analysis demonstrated no significant difference in mortality rates between patients with and without TA (P = 0.065). After multivariate Cox-analysis (HR: 0.94, 95% CI 0.641–1.383) and the addition of propensity matching (HR: 0.86 95% CI 0.412–1.798) TA was still not associated with decreased mortality. By contrast, in hyperglycemic subgroup STEMI patients (TA-group, n = 331; no-TA group, n = 566), Kaplan–Meier-analysis demonstrated a significantly lower mortality (P = 0.019) in TA-group than the no-TA group. After multivariate Cox-analysis (HR: 0.64, 95% CI 0.379–0.963) and the addition of propensity matching (HR: 0.54, 95% CI 0.294–0.984) TA was still associated with decreased mortality. Conclusions TA was not associated with lower mortality in PPCI for STEMI when used in our large all-comer cohort. Conversely, TA during PPCI for STEMI reduces clinical outcomes in hyperglycemic patients. Trial registration NCT02817542. 25th, June 2016

Background No proper data on prognosis and management of type-2 diabetic ST elevation myocardial infarction (STEMI) patients with culprit obstructive lesion and multivessel non obstructive coronary stenosis (Mv-NOCS) exist. We evaluated the 12-months prognosis of Mv-NOCS-diabetics with first STEMI vs.to non-diabetics, and then Mv-NOCS-diabetics previously treated with incretin based therapy vs. a matched cohort of STEMI-Mv-NOCS never treated with such therapy. Methods 1088 Patients with first STEMI and Mv-NOCS were scheduled for the study. Patients included in the study were categorized in type 2 diabetics (n 292) and non-diabetics (n 796). Finally, we categorized diabetics in current-incretin-users (n 76), and never-incretin-users (n 180). The primary end point was all cause deaths, cardiac deaths, and major adverse cardiac events (MACE) at 12 months of follow up. Results The study results evidenced higher percentage of all cause deaths (2.2% vs. 1.1%, p value 0.05), cardiac deaths (1.6% vs. 0.5%, p value 0.045), and MACE (12.9% vs. n 5.9%), p value 0.001) in diabetic vs. no diabetic patients at 12 months follow up. Among diabetic patients, the current vs never-incretin-users, did not present a significant difference about all cause of deaths, and cardiac deaths through 12-months. The MACE rate at 1 year was 7.4% in diabetic incretin-users STEMI Mv-NOCS patients vs. 12.9% in diabetic never-incretin-users STEMI-Mv-NOCS patients (p value 0.04). In a risk-adjusted hazard analysis, MACE through 12 months were lower in diabetic STEMI-Mv NOCS incretin-users vs never-incretin-users patients (HR 0.513, CI [0.292–0.899], p 0.021). Consequently, lower levels of glucagon-like peptide 1(GLP-1) were predictive of MACE at follow up (HR 1.528, CI [1.059–2.204], p 0.024). Conclusion In type 2 diabetic patients with STEMI-Mv-NOCS, we observed higher incidence of 1-year mortality and adverse cardiovascular outcomes, as compared to non-diabetic STEMI-Mv-NOCS patients. In diabetic patients, never-incretin-users have worse prognosis as compared to current-incretin-users. Trail registration Clinical trial number: NCT03312179, name of registry: clinicaltrialgov, URL: clinicalltrialgov.com, date of registration: September 2017, date of enrollment first participant: September 2009

Objective A previous European cost-utility study reported that use of buccal midazolam in the community setting for the treatment of prolonged seizures (ie, seizures lasting ≥5 minutes) in children was associated with an overall €12 507 399 reduction in annual costs charged to the Italian national health service compared with rectal diazepam. We re-evaluated these findings by applying a more conservative approach. Methods The Italian Delphi panel reconvened to apply a more conservative assessment of available reports. A decision-tree model was used, allowing for different treatment pathways depending on whether or not a caregiver administers treatment, an ambulance is required for transport of the child to hospital, and an inpatient stay is required. Direct medical costs were derived from Italian healthcare system data. Estimates of the annual number of prolonged tonic-clonic seizures expected in the country were based on studies which assessed seizure duration using video-EEG recordings and medical records. Results Although drug acquisition costs were greater for buccal midazolam than for rectal diazepam, the acquisition cost difference was outweighed by larger cost savings resulting mostly from a reduction in hospital admissions. Assuming that 1.2% of tonic and/or clonic seizures occurring in children and adolescents over a 12-month period are prolonged, the annual nationwide reduction in costs from preferring buccal midazolam to rectal diazepam was estimated at €3 577 587.9. Conclusions In this more conservative revised analysis, the high cost of buccal midazolam is still counteracted by greater cost savings compared with rectal diazepam, but cost reduction was less than previously estimated.

Aim: Hypoxic-ischemic-encephalopathy is a severe and frequent neurological complication of successful cardiopulmonary-resuscitation after cardiac arrest. Prognosticating neurological outcomes in patients with hypoxic-ischemic-encephalopathy is challenging and recent guidelines suggest a multimodal approach. Only few studies have analyzed the prognostic power of the association between instrumental tests and, in addition, most of them were monocentric, retrospective and evaluating only poor outcome. Methods/design: We designed a multicenter prospective cohort study to assessing the prognostic power of the association of electroencephalogram and somatosensory evoked potentials for the prediction of both poor and good neurological outcomes at different times after cardiac arrest. Discussion: The results of our study will provide a high level of evidence for the use of neurophysiological evaluation in the current clinical practice.

Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency.

SEPs are reliable predictor of poor outcome in comatose patients after cardiac arrest (CA). Recently also the role of EEG has been reassessed. To evaluate the prognostic value of EEG and SEPs association in post-anoxic coma at different recording time. We included comatose patients after CA. EEG and SEPs were recorded within 12 hs and at 72 hs after CA. EEG was classified into grade 1(“continuous”/“nearly-continuous”) and grade 2(discontinuous/burst-suppression/suppression/isoelectric). SEPs were dichotomized into “bilaterally absent” (BA) and “present”. Outcome was evaluated at 6 months by GOS. “Recovery of consciousness” was considered good outcome. Ten centers took part to the study and 282 patients were included. EEG and SEPs were recorded in 141 within 12 hs in 162 at 72 hs. Grade 1 EEG at 12 hs always predicted good outcome, grade 2 pattern at 72 hs predicted poor outcome with higher predictive power. BA SEPs always predicted poor outcome. Grade 1 EEG was always associated with present SEPs. EEG is a reliable time-dependent predictor of good outcome (within 12 h) and poor outcome (after 72 h). SEP is time-independent predictor of poor outcome. Early grade 1 EEG is never associated with BA SEP. Early association recordings of EEG and SEPs increase of the reliability of prognosis prediction in post-anoxic coma.

Somatosensory evoked potentials(SEPs) and EEG are reliable outcome predictors of coma after cardiac arrest (CA). Nevertheless, only few multicentric studies are available. Aim of the study was to evaluate the prognostic value of EEG and SEPs association in post-anoxic comatose patients at different recording time from cardiac arrest (CA) in an Italian multicentric study. Comatose patients after CA treated with TH were included. EEG and SEPs were recorded within 12 h and at 72 h after CA. EEG was classified into “non-continuous” and “continuous”. SEPs were dichotomized into “bilaterally absent” (BA) and “present”. Neurologic outcome was evaluated at 6 months by GOS: “awakening”(GOS 3–5) was considered good outcome. 83 patients were included to date. “Continuous” EEG pattern at 12 h always predicted good outcome, “non-continuous” pattern at 72 h always predicted poor outcome. BA SEPs always predicted poor outcome. Early “continuous” EEG pattern was always associated with present SEPs. SEPs provide a specific and time-independent predictor of poor outcome. EEG provide a specific and time-dependent predictor of good outcome (at