Efficacy of ketamine in refractory convulsive status epilepticus in children: A protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01)

Introduction: Status epilepticus (SE) is a lifethreatening neurological emergency. SE lasting longer than 120 min and not responding to first-line and second-line antiepileptic drugs is defined as 'refractory' (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-D-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE. Methods and analysis: A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/ hospitals are involved in enrolling 57 patients aged 1 month to 18 years with RCSE. Primary outcome is the resolution of SE up to 24 hours after withdrawal of therapy and is updated for each patient treated according to the sequential method. Ethics and dissemination: The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences

Management and Nutrition of Neonates during the COVID-19 Pandemic: A Review of the Existing Guidelines and Recommendations

We aimed at reviewing the currently available guidelines and scientific recommendations regarding the neonatal in-hospital management and feeding in the light of the coronavirus disease 2019 (COVID-19) pandemic

Microglia and Other Cellular Mediators of Immunological Dysfunction in Schizophrenia: A Narrative Synthesis of Clinical Findings

Schizophrenia is a complex psychiatric condition that may involve immune system dysregulation. Since most putative disease mechanisms in schizophrenia have been derived from genetic association studies and fluid-based molecular analyses, this review aims to summarize the emerging evidence on clinical correlates to immune system dysfunction in this psychiatric disorder. We conclude this review by attempting to develop a unifying hypothesis regarding the relative contributions of microglia and various immune cell populations to the development of schizophrenia. This may provide important translational insights that can become useful for addressing the multifaceted clinical presentation of schizophrenia

Chronotype and Cardiometabolic Parameters in Patients with Bipolar Disorder: Preliminary Findings

Cardiometabolic alterations are very common in bipolar disorder (BD). The aim of this study was to investigate the relationship between chronotype and cardiometabolic parameters in patients with a primary diagnosis of BD. This study is an observational clinical investigation including 170 subjects consecutively admitted to the Psychiatric Inpatient Unit of the IRCCS Ospedale Policlinico San Martino (Genoa, Italy), recruited over a period of 48 months. A psychometric tool assessing chronotype was administered and blood tests were performed. Furthermore, the atherogenic coefficient ((total cholesterol-HDL cholesterol)/HDL cholesterol), and Castelli risk index-I (total cholesterol/HDL cholesterol) and -II (LDL cholesterol/HDL cholesterol) were calculated. Patients with BD and an eveningness chronotype showed a higher body mass index, total and low-density lipotrotein cholesterol compared to patients with BD and an intermediate or morning chronotype. Furthermore, the Atherogenic Coefficient and Castelli Risk-Index I-II were found to be higher in bipolar patients with an evening chronotype. The role of chronotype in the development of obesity and cardiovascular risk is, therefore, a relationship worth being investigated, especially in the context of BD, to ameliorate the clinical and therapeutic approach, aiming at increasing the quality of life and reducing the mortality

Mechanical Restraint in Inpatient Psychiatric Unit: Prevalence and Associated Clinical Variables

Background and Objectives: mechanical restraint (MR) is a controversial issue in emergency psychiatry and should be better studied to implement other alternative therapeutic interventions. The aim of this study was to estimate the prevalence of MR in an Italian psychiatric unit and identify the sociodemographic and clinical characteristics as well as the pharmacological pattern associated with MR. Materials and Methods: all subjects (N = 799) consecutively admitted to an Italian psychiatric inpatient unit were recruited. Several sociodemographic and clinical characteristics were recorded. Results: The prevalence of MR was 14.1%. Males, a younger age, and a single and migrant status were associated with the MR phenomenon. MR was more prevalent in patients affected by other diagnoses and comorbid illicit substance use, in patients with aggressive behaviors, and those that were involuntary admitted, leading significantly to hospitalization over 21 days. Furthermore, the patients that underwent MR were taking a lower number of psychiatric medications. Conclusions: Unfortunately, MR is still used in emergency psychiatry. Future research should focus on the dynamics of MR development in psychiatry, specifically considering ward- and staff-related factors that could help identify a more precise prevention and alternative intervention strategies

Intrahepatic Administration of Human Liver Stem Cells in Infants with Inherited Neonatal-Onset Hyperammonemia: A Phase I Study

Previous studies have shown that human liver stem-like cells (HLSCs) may undergo differentiation in vitro into urea producing hepatocytes and in vivo may sustain liver function in models of experimentally induced acute liver injury. The aim of this study was to assess the safety of HLSCs intrahepatic administration in inherited neonatal-onset hyperammonemia. The study was approved by the Agenzia Italiana del Farmaco on favorable opinion of the Italian Institute of Health as an open-label, prospective, uncontrolled, monocentric Phase I study (HLSC 01-11, EudraCT-No. 2012-002120-33). Three patients affected by argininosuccinic aciduria (patient 1) and methylmalonic acidemia (patients 2 and 3) and included in the liver transplantation list were enrolled. In all patients, HLSCs were administered by percutaneous intrahepatic injections (once a week for two consecutive weeks) within the first months of life. The first patient received 125,000 HLSCs x gram of liver/dose while the other two patients received twice this dose. No immunosuppression was administered since HLSCs possess immunomodulatory activities. None of the patients experienced infections, hyperammonemia decompensation, or other adverse events during the whole observation period. No donor specific antibodies (DSA) against HLSCs were detected. Patients were metabolic stable despite an increase (~30%) in protein intake. Two patients underwent liver transplantation after 19 and 11 months respectively, and after explantation, the native livers showed no histological alterations. In conclusion, percutaneous intrahepatic administration of HLSCs was safe in newborn with inherited neonatal-onset hyperammonemia. These data pave the way for Phase II studies in selected inherited and acquired liver disorders

KETASER01 protocol: What went right and what went wrong

To discuss the results of the KETASER01 trial and the reasons for its failure, particularly in view of future studies

Neurological abnormalities in full-term asphyxiated newborns and salivary S100B testing: the “cooperative multitask against brain injury of neonates” (CoMBINe) international study

BACKGROUND: Perinatal asphyxia (PA) is a leading cause of mortality and morbidity in newborns: its prognosis depends both on the severity of the asphyxia and on the immediate resuscitation to restore oxygen supply and blood circulation. Therefore, we investigated whether measurement of S100B, a consolidated marker of brain injury, in salivary fluid of PA newborns may constitute a useful tool for the early detection of asphyxia-related brain injury. METHODS: We conducted a cross-sectional study in 292 full-term newborns admitted to our NICUs, of whom 48 suffered PA and 244 healthy controls admitted at our NICUs. Saliva S100B levels measurement longitudinally after birth; routine laboratory variables, neurological patterns, cerebral ultrasound and, magnetic resonance imaging were performed. The primary end-point was the presence of neurological abnormalities at 12-months after birth. RESULTS: S100B salivary levels were significantly (P3.25 MoM S100B achieved a sensitivity of 100% (CI5-95%: 89.3%-100%) and a specificity of 100% (CI5-95%: 98.6%-100%) as a single marker for predicting the occurrence of abnormal neurological outcome (area under the ROC curve: 1.000; CI5-95%: 0.987-1.0). CONCLUSIONS: S100B protein measurement in saliva, soon after birth, is a useful tool to identify which asphyxiated infants are at risk of neurological sequelae

Saliva levels of S100B in neonates with normal, BG/W score 1–2 and BG/W score 3–4.

<p>The box plots represent the medians and interquartile ranges for each group. ^*^*P<0.001 global BG/W vs severe BG/W injury; ^*P<0.001 vs normal MRI group.</p