RESUMO
Traumatic brain injury is often accompanied by defects in hormone levels, caused by either peripheral gland dysfunctions or by an insufficient central stimulation of hormone production. The epidemiology of endocrinological defects after traumatic brain injury is quite well described, but the consequences of hormone defects are largely unknown, especially in paediatric patients undergoing neurological rehabilitation. Only one previous study reported on a cohort of 20 children with traumatic brain injury and found a low incidence of hormone defects and a correlation between some hormone levels and neurological recovery. In this study, we performed a retrospective chart review on patients affected by severe subacute traumatic brain injury. Their levels of cortisol, ACTH, IGF-1, TSH, free T4, free T3, and prolactin were collected and compared with reference ranges; we then used regression models to highlight any correlation among them and with clinical variables; last, we probed with regression models whether hormone levels could have any correlation with clinical and rehabilitation outcomes. We found eligible data from the records of 52 paediatric patients with markedly severe traumatic brain injury, as shown by an average GCS of 4.7; their age was 10.3 years, on average. The key results of our study are that 32% patients had low IGF-1 levels and in multiple regression models, IGF-1 levels were correlated with neurological recovery, indicating a possible role as a biomarker. Moreover, 69% of patients had high prolactin levels, possibly due to physical pain and high stress levels. This study is limited by the variable timing of the IGF-1 sampling, between 1 and 2 months after injury. Further studies are required to confirm our exploratory findings.
RESUMO
The metabolic effects induced by antipsychotics in vitro depend on their action on the trafficking and biosynthesis of sterols and lipids. Previous research showed that antipsychotics with different adverse effects in patients cause similar alterations in vitro, suggesting the low clinical usefulness of cellular studies. Moreover, the inhibition of peripheral AMPK was suggested as potential aetiopathogenic mechanisms of olanzapine, and different effects on autophagy were reported for several antipsychotics. We thus assessed, in clinically-relevant culture conditions, the aetiopathogenic mechanisms of olanzapine, risperidone and ziprasidone, antipsychotics with respectively high, medium, low metabolic risk in patients, finding relevant differences among them. We highlighted that: olanzapine impairs lysosomal function affecting autophagy and autophagosome clearance, and increasing intracellular lipids and sterols; ziprasidone activates AMPK increasing the autophagic flux and reducing intracellular lipids; risperidone increases lipid accumulation, while it does not affect lysosomal function. These in vitro differences align with their different impact on patients. We also provided evidence that metformin add-on improved autophagy in olanzapine-treated cells and reduced lipid accumulation induced by both risperidone and olanzapine in an AMPK-dependent way; metformin also increased the production of bile acids to eliminate cholesterol accumulations caused by olanzapine. These results have different clinical implications. We demonstrated that antipsychotics with different metabolic impacts on patients actually have different mechanisms of action, thus supporting the possibility of a personalised antipsychotic treatment. Moreover, we found that metformin can fully revert the phenotype caused by risperidone but not the one caused by olanzapine, that still activates SREBP2.
Assuntos
Antipsicóticos , Metformina , Humanos , Risperidona/farmacologia , Olanzapina/farmacologia , Proteínas Quinases Ativadas por AMP , Antipsicóticos/efeitos adversos , Autofagia , Esteróis , LisossomosRESUMO
INTRODUCTION: The RISKMet project aims to: (1) identify risk factors for metabolic syndrome (MetS) by comparing patients with and without MetS; (2) characterise patients treated with second-generation antipsychotics (SGAs) about MetS diagnosis; (3) study behavioural patterns, including physical activity (PA) and dietary habits, in patients and healthy individuals using a prospective cohort design. METHOD: The RISKMet project investigates MetS in individuals treated with SGAs, focusing on both adult and paediatric populations. The study utilizes a case-control design to examine potential risk factors for MetS, categorizing participants as MetS+ considered as "Cases" and MetS- considered as "Controls" matched by sex and age. The evaluation of factors such as MetS, lifestyle habits, and environmental influences is conducted at two time points, T0 and T3, after 3 months. Subsequently, the project aims to assess body parameters, including physical examinations, and blood, and stool sample collection, to evaluate metabolic markers and the impact of SGAs. The analysis includes pharmacological treatment data and genetic variability. Behavioural markers related to lifestyle, eating behaviour, PA, and mood are assessed at both T0 and T3 using interviews, accelerometers, and a mobile app. The study aims to improve mental and physical well-being in SGA-treated individuals, establish a biobank for MetS research, build an evidence base for physical health programs, and develop preventive strategies for SGA-related comorbidities. CONCLUSIONS: This project innovates MetS monitoring in psychiatry by using intensive digital phenotyping, identifying biochemical markers, assessing familial risks, and including genetically similar healthy controls. STUDY REGISTRATION NUMBER: ISRCTN18419418 at www.isrctn.com.
Assuntos
Antipsicóticos , Síndrome Metabólica , Humanos , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/genética , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Fatores de Risco , Masculino , Feminino , Adulto , Estudos de Casos e Controles , Estudos Prospectivos , Estilo de Vida , Exercício Físico , Pessoa de Meia-Idade , CriançaRESUMO
BACKGROUND: We evaluated the effect of rapid ART (RA) compared to delayed ART (DA) on viral load suppression (viral load <50 cp/mL) and loss to follow-up (LTFU) in a cohort of migrants living with HIV (MLWHs) in Italy. METHODS: Data were retrospectively gathered from MLWHs who began care at the Infectious and Tropical Diseases Unit of the Careggi University Hospital from January 2014 to December 2022. RA was defined as antiretrovirals prescribed within 7 days of HIV diagnosis. The study ended on April 30, 2023, or upon patient LTFU. Chi-square and non-parametric tests assessed differences in categorical and continuous variables, respectively. Kaplan-Meyer survival analysis was performed to estimate the probability of loss to follow-up. Cox regression analysis was performed to evaluate factors associated with a loss to follow-up. RESULTS: 87 MLWHs were enrolled: 20 (23%) on RA and 67 (77%) on DA. In the RA group there were more PLWH with a previous AIDS event (p < .001) however, there was no significant difference in the LTFU rates between the groups (aHR 0.6, 95%CI 0.1-3.1; p = .560; Logrank = 0.2823). Being an out-of-status MLWH was the only predictor of LTFU. By 6 months, virological suppression was achieved in 61.2% (n = 41) in DA and 70.0% in the RA group (n = 14) (Logrank p = .6747). CONCLUSIONS: RA did not significantly affect LTFU rates or the achievement of viral load suppression. The study suggests that further research is needed to assess the impact of RA in high income settings.