Andexanet Alfa versus Four-Factor Prothrombin Complex Concentrate for the Reversal of Factor Xa (FXa) Inhibitor-Associated Intracranial Hemorrhage: A Systematic Review of Retrospective Studies.

Background/Objectives: There are limited data on the risks and benefits of using Andexanet alfa (AA) compared with four-factor prothrombin complex concentrate (4F-PCC) for the reversal of factor Xa inhibitor-associated intracranial hemorrhage (ICH). Our aim was to describe a compilation of the information available in the literature to date. Methods: PubMed, Embase, Web of Science (Clarivate Analytics) and the Cochrane Central Register of Controlled Trials were searched until December 2023. Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines, our systematic literature review included studies that were retrospective in design and evaluated both drugs to control bleeding and complications (death and thromboembolic events). Two researchers re-examined the studies for relevance, extracted the data and assessed the risk of bias. No meta-analyses were performed for the results. Results: In this limited patient sample, we found no differences between published articles in terms of neuroimaging stability or thrombotic events. However, some studies show significant differences in mortality, suggesting that one of the AAs may be superior to 4F-PCC. Conclusions: Our qualitative analysis shows that AA has a better efficacy profile compared with 4F-PCC. However, further studies monitoring these patients and a multicenter collaborative network dedicated to this topic are needed.

Biochemical Changes in Cardiopulmonary Bypass in Cardiac Surgery: New Insights.

Patients undergoing coronary revascularization with extracorporeal circulation or cardiopulmonary bypass (CPB) may develop several biochemical changes in the microcirculation that lead to a systemic inflammatory response. Surgical incision, post-CPB reperfusion injury and blood contact with non-endothelial membranes can activate inflammatory signaling pathways that lead to the production and activation of inflammatory cells, with cytokine production and oxidative stress. This inflammatory storm can cause damage to vital organs, especially the heart, and thus lead to complications in the postoperative period. In addition to the organic pathophysiology during and after the period of exposure to extracorporeal circulation, this review addresses new perspectives for intraoperative treatment and management that may lead to a reduction in this inflammatory storm and thereby improve the prognosis and possibly reduce the mortality of these patients.

The GPER1 agonist G1 reduces brain injury and improves the qEEG and behavioral outcome of experimental ischemic stroke.

Stroke is one of the principal cerebrovascular diseases in human populations and contributes to a majority of the functional impairments in the elderly. Recent discoveries have led to the inclusion of electroencephalography (EEG) in the complementary prognostic evaluation of patients. The present study describes the EEG, behavioral, and histological changes that occur following cerebral ischemia associated with treatment by G1, a potent and selective G protein-coupled estrogen receptor 1 (GPER1) agonist in a rat model. Treatment with G1 attenuated the neurological deficits induced by ischemic stroke from the second day onward, and reduced areas of infarction. Treatment with G1 also improved the total brainwave power, as well as the theta and alpha wave activity, specifically, and restored the delta band power to levels similar to those observed in the controls. Treatment with G1 also attenuated the peaks of harmful activity observed in the EEG indices. These improvements in brainwave activity indicate that GPER1 plays a fundamental role in the mediation of cerebral injury and in the behavioral outcome of ischemic brain injuries, which points to treatment with G1 as a potential pharmacological strategy for the therapy of stroke.

Nasotracheal intubation awake in a patient with multiple fractures of the maxilla and cervical spine: A case report.

RATIONALE: Nasotracheal intubation is an advanced airway modality used in specific contexts, such as limited mouth opening, macroglossia, cervical spine instability. In addition, it can be performed with the patient awake, especially when predictors a difficult airway are unknown. PATIENT CONCERNS: A 41-year-old male with a lesion in the C1 cervical vertebra, associated with a fracture of the right maxilla, was intubated through the nasopharyngeal route while awake. The forms of induction were discussed. DIAGNOSES: Based on the mechanism of trauma and on the report of pain, associated with imaging examination, fracture of the body of the right maxilla and a complex fracture of the anterior arch of the C1 cervical vertebra were diagnosed. INTERVENTIONS: In this case, we present a patient with trauma to the face and spine who was intubated through the nasopharyngeal route while awake and guided by video laryngoscopy and using a rigid cervical collar. The patient was operated on under total general anesthesia (propofol and remifentanil) and plates and screws were placed for maxillary osteosynthesis. The pain was alleviated with a peripheral block of the trigeminal nerve of the maxillary branch with 0.5% levobupivacaine. OUTCOMES: The patient woke up from surgery, was extubated uneventfully and without pain. Cervical spine injuries were followed up by the neurosurgery team for conservative treatment. LESSONS: Patients with neck injury and facial trauma may need a definitive airway either for emergencies or for elective procedures. Intubating the awake patient may be an option when the anatomy of the cavity is unknown, and inducing the anesthetic act without this knowledge may be a inappropriate option, due to the risk of intubation/ventilation difficulties.

Oral Treatment with the Extract of Euterpe oleracea Mart. Improves Motor Dysfunction and Reduces Brain Injury in Rats Subjected to Ischemic Stroke.

Ischemic stroke is one of the principal causes of morbidity and mortality around the world. The pathophysiological mechanisms that lead to the formation of the stroke lesions range from the bioenergetic failure of the cells and the intense production of reactive oxygen species to neuroinflammation. The fruit of the açaí palm, Euterpe oleracea Mart. (EO), is consumed by traditional populations in the Brazilian Amazon region, and it is known to have antioxidant and anti-inflammatory properties. We evaluated whether the clarified extract of EO was capable of reducing the area of lesion and promoting neuronal survival following ischemic stroke in rats. Animals submitted to ischemic stroke and treated with EO extract presented a significant improvement in their neurological deficit from the ninth day onward. We also observed a reduction in the extent of the cerebral injury and the preservation of the neurons of the cortical layers. Taken together, our findings indicate that treatment with EO extract in the acute phase following a stroke can trigger signaling pathways that culminate in neuronal survival and promote the partial recovery of neurological scores. However, further detailed studies of the intracellular signaling pathways are needed to better understand the mechanisms involved.

A Combination of Curcuma longa and Diazepam Attenuates Seizures and Subsequent Hippocampal Neurodegeneration.

Epilepsy is one of the most common neurological disorders, which occurs due to the instability in the inhibitory and excitatory synaptic transmissions in the brain. However, many patients develop resistance to the available drugs, which results in cell degeneration caused due to inadequate control of the seizures. Curcumin, Curcuma longa, is known to be effective for the treatment of organic disorders and may prevent seizures, reduce oxidative stress, and decrease brain damage. Given this, the present study evaluated the antiepileptic effects of C. longa in comparison with both the diazepam and the combined application of these two substances, in terms of their effects on the brain activity and the potential histopathological changes in the hippocampus. This study used male Wistar rats (age: 10-12 weeks; weight: 260 ± 20 g), which were pretreated for 4 days with either saline, C. longa, diazepam, or C. longa + diazepam; and on the fifth day, pentylenetetrazol (PTZ) was administered to induce the seizure. In the C. longa group, a significant increase was observed in the latency of the onset of seizure-related behavior. Surprisingly, however, the combined treatment resulted in the best control of the seizure-related behavior, with the greatest latency of the onset of spasms and isolated clonic seizures. This group also obtained the best results in the electroencephalographic trace and seizure control, with a reduction in the frequency and amplitude of the spike-waves. In the saline group, PTZ significantly reduced the number of cells present in the CA1 and CA3 regions of the hippocampus, while the combined treatment obtained the best results in terms of the preservation of the neuron-like cells. These findings indicate that C. longa may contribute to the control of both seizures and the cell damage induced by PTZ, and that its association with diazepam may be a potentially effective option for the treatment of epilepsy in the future.

Increased Relative Delta Bandpower and Delta Indices Revealed by Continuous qEEG Monitoring in a Rat Model of Ischemia-Reperfusion.

The present study describes the electroencephalographic changes that occur during cerebral ischemia and reperfusion in animals submitted to transient focal cerebral ischemia by middle cerebral artery occlusion (MCAO) for 30 min. For this, male Wistar rats were divided into two groups (n = 6 animals/group): (1) sham (control) group, and (2) ischemic/reperfusion group. The quantitative electroencephalography (qEEG) was recorded during the ischemic and immediate reperfusion (acute) phases, and then once a day for 7 days after the MCAO (subacute phase). The acute phase was characterized by a marked increase in the relative delta wave band power (p < 0.001), with a smaller, but significant increase in the relative alpha wave bandpower in the ischemic stroke phase, in comparison with the control group (p = 0.0054). In the immediate reperfusion phase, however, there was an increase in the theta, alpha, and beta waves bandpower (p < 0.001), but no alteration in the delta waves (p = 0.9984), in comparison with the control group. We also observed high values in the delta/theta ratio (DTR), the delta/alpha ratio (DAR), and the (delta+theta)/(alpha+beta) ratio (DTABR) indices during the ischemia (p < 0.05), with a major reduction in the reperfusion phase. In the subacute phase, the activity of all the waves was lower than that of the control group (p < 0.05), although the DTR, DAR, and DTABR indices remained relatively high. In conclusion, early and accurate identification of decreased delta wave bandpower, DTR, DAR, and DTABR indices, and an increase in the activity of other waves in the immediate reperfusion phase may represent an important advance for the recognition of the effectiveness of reperfusion therapy.

Electrocorticographic description of the effects of anticonvulsant drugs used to treat lidocaine-induced seizures.

INTRODUCTION: Local anesthetics are widely used in clinical practice. While toxicity is rare, these drugs can cause potentially lethal seizures. OBJECTIVE: In the present study, we investigated the electrocorticographic (ECoG) and electromyographic patterns of seizures induced by acute lidocaine (LA) toxicity and treated with anticonvulsant drugs. The study used adult male Wistar rats to describe of the seizure-related behavior of LA and investigated the treatment with anticonvulsant drugs. RESULTS: The use of LA resulted in clear changes in the ECoG pattern, which presented characteristics of Status epilepticus, with increased intensity in all brainwaves. The decomposition of the cerebral waves showed an increase in the beta and gamma waves that may be related to tonic-clonic seizure. Although the treatment with anticonvulsants drugs reduces the power of brainwaves at frequencies between 1 and 40 Hz compared to the LA group, but only diazepam (DZP) was able to decrease the intensity of oscillations. The muscle contraction power also indicated a difference in the effectiveness of the three treatments. CONCLUSION: The sum of the evidence indicates that LA causes status epilepticus and that DZP is the most effective treatment for the control of these seizures, by restoring the systemic values to levels close to those recorded in the control group.

Electrocorticographic patterns dominated by low-frequency waves in camphor-induced seizures.

Camphor is an aromatic terpene compound found in the essential oils of many plants, which has been used for centuries as a herbal medicine, especially in children. However, many studies have shown that camphor may have major side effects, including neurological manifestation, such as seizures. In the present study, we investigated the electrocorticographic patterns of seizures induced by camphor in male adult Wistar rats. Each rat received 400 mg/kg (i.p.) of camphor prior to monitoring by electrocorticography. The application of camphor resulted a rapid evolution to seizure and marked changes in the electrocorticographic readings, which presented characteristics of epileptiform activity, with an increase in the total power wave. The decomposition of the cerebral waves revealed an increase in the delta and theta waves. The analysis of the camphor traces revealed severe ictal activity marked by an increase in the polyspike wave. Our data thus indicate that camphor may cause seizures, leading to tonic-clonic seizures. Clearly, further studies are necessary to better elucidate the mechanisms through which camphor acts on the brain, and to propose potential treatments with anticonvulsant drugs that are effective for the control of the seizures.

Spatio-temporal analysis of leptospirosis in Eastern Amazon, State of Pará, Brazil.

INTRODUCTION: Brazil has registered more than 62,000 confirmed cases of leptospirosis between 2001 and 2017, with more than 2,000 cases confirmed in the State of Pará. Despite a large number of cases, no study has been conducted to trace the spatio-temporal profile of the disease. METHODOLOGY: Confirmed cases of leptospirosis from 2001 to 2017 from the state of Pará were the basis for this space-time study. The database of the Department of Informatics of the Ministry of Health was used to access data on leptospirosis. The spatio-temporal analysis was performed in the SaTScan software for the detection of clusters, and maps were generated in the QGIS software. RESULTS: The municipalities of Belém and Santarém were among the ones with the highest incidence rates of leptospirosis for the whole study period. Increased number of cases in Soure, Inhangapi, São João da Ponta and Magalhães Barata, Ponta de Pedras, Breves, Bragança, Castanhal, and São Domingos do Capim were identified in different time periods. Santarém and Belém are the main foci of leptospirosis because they are the most urbanized and densely populated municipalities in the State. The cases found in smaller municipalities may be associated with periods of more frequent rainfall and circulation of Leptospira sp. in marsupials and cattle, in the northeastern part of the State. CONCLUSION: Further studies are needed to help identify the risk factors that contribute to the occurrence of leptospirosis in the State of Pará, particularly in areas with lower population density.

Spatio-temporal analysis of leptospirosis in Eastern Amazon, State of Pará, Brazil / Análise espaço-temporal da leptospirose na Amazônia Oriental, Estado do Pará, Brasil

ABSTRACT: Introduction: Brazil has registered more than 62,000 confirmed cases of leptospirosis between 2001 and 2017, with more than 2,000 cases confirmed in the State of Pará. Despite a large number of cases, no study has been conducted to trace the spatio-temporal profile of the disease. Methodology: Confirmed cases of leptospirosis from 2001 to 2017 from the state of Pará were the basis for this space-time study. The database of the Department of Informatics of the Ministry of Health was used to access data on leptospirosis. The spatio-temporal analysis was performed in the SaTScan software for the detection of clusters, and maps were generated in the QGIS software. Results: The municipalities of Belém and Santarém were among the ones with the highest incidence rates of leptospirosis for the whole study period. Increased number of cases in Soure, Inhangapi, São João da Ponta and Magalhães Barata, Ponta de Pedras, Breves, Bragança, Castanhal, and São Domingos do Capim were identified in different time periods. Santarém and Belém are the main foci of leptospirosis because they are the most urbanized and densely populated municipalities in the State. The cases found in smaller municipalities may be associated with periods of more frequent rainfall and circulation of Leptospira sp. in marsupials and cattle, in the northeastern part of the State. Conclusion: Further studies are needed to help identify the risk factors that contribute to the occurrence of leptospirosis in the State of Pará, particularly in areas with lower population density.

RESUMO: Introdução: O Brasil registrou mais de 62 mil casos de leptospirose confirmados entre 2001 e 2017, com mais de 2.000 casos confirmados no estado do Pará. Apesar da grande quantidade de casos, nenhum estudo até este momento traçou o perfil espaço-temporal da doença. Metodologia: Este é um estudo espaço-temporal com base nos casos confirmados de leptospirose entre 2001 a 2017 no estado do Pará. O banco de dados do Departamento de Informática do Ministério da Saúde foi utilizado para acessar os dados de leptospirose. A análise espaço-temporal foi realizada no software SaTScan para detecção de clusters e os mapas foram gerados no software QGIS. Resultados: O município de Belém e Santarém se mantiveram entre as maiores taxas de incidência de leptospirose durante todo o período estudado. O aumento no número de casos em Soure, Inhangapi, São João da Ponta e Magalhães Barata, Ponta de Pedras, Breves, Bragança, Castanhal e São Domingos do Capim foram identificados em diferentes períodos. Santarém e Belém são os principais focos de leptospirose por serem os municípios mais urbanizados e com maior densidade populacional do estado. Os casos observados em municípios menores podem estar associados a períodos de maior pluviosidade e circulação de Leptospira sp. em marsupiais e em gado no nordeste do estado. Conclusão: Com o exposto, torna-se necessário mais estudos visando o conhecimento dos fatores que contribuem com a ocorrência da leptospirose no estado do Pará, particularmente em áreas com menor adensamento populacional.

Alteration of Testosterone Levels Changes Brain Wave Activity Patterns and Induces Aggressive Behavior in Rats.

Testosterone is responsible for several changes in the brain, including behavioral and emotional responses, memory, and cognition. Given this, we investigated changes in the brain wave profile caused by supplementation with exogenous testosterone in both castrated and non-castrated rats. We also investigated the serum testosterone levels, renal and hepatic function, and the lipid and behavioral profiles. We found changes in the spectral wave power in both groups (castrated and non-castrated animals) supplemented with exogenous testosterone, consistent with an aggressive/hostile profile. These changes were observed in the electrocorticographic evaluation associated with increased power in low-frequency (delta and theta) and high-frequency (beta and gamma) activity in the supplemented animals. The castrated animals presented a significant decrease of wave power in the alpha frequency. This correlated with a decrease of the performance of the animals in the elevated plus-maze evaluation, given that the alpha wave is linked to the execution and visualization of motor processes. In the behavioral evaluation, the castrated animals presented a reduced permanence time in the elevated-plus maze, although this was prevented by the supplementation of testosterone. Testosterone supplementation induced aggressive behavior in non-castrated animals, but not in castrated ones. Supplemented animals had significantly elevated serum testosterone levels, while their urea levels were significantly lower, but without clinical significance. Our data indicate that testosterone supplementation in non-castrated rats, but not in castrated ones, causes electrocorticographic changes that could be associated with more aggressive and hostile behavior, in addition to indicating a potential for personality disorder. However, further studies are required to elucidate the cellular and molecular changes caused by acute testosterone supplementation.