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Study Objective: We hypothesized that the use of inhaled alkaloidal ("crack") cocaine could increase lung content of iron, either by inducing alveolar hemorrhage or by other mechanisms. Intrapulmonary accumulation of iron could promote chronic lung diseases in crack users. The goal of this study was to determine whether iron and ferritin content of alveolar macrophages or fluid recovered by BAL was increased in subjects using crack, compared with nonsmokers.Methods: BAL was performed in 31 volunteer subjects, including healthy nonsmokers (n = 7), subjects smoking crack alone (n = 7), as well as subjects smoking both crack and cigarettes (n = 7) or cigarettes alone (n = 10). Iron content of alveolar macrophages and BAL fluid was determined by a colorimetric method and ferritin content of alveolar macrophages, and BAL fluid was measured by a two-sided immunoradiometric method.Results: Alveolar macrophages recovered from crack users contained more iron than did alveolar macrophages from nonsmokers (25.4 +/- 2.9 nmol/10(6) vs 5.5 +/- 0.6 nmol/10(6) [mean +/- SE]; p < 0.01). There were similar increases in alveolar macrophage ferritin as well as BAL fluid iron and ferritin in crack users, compared with nonsmokers. BAL fluid ferritin concentrations in subjects smoking both crack and cigarettes were increased, compared with subjects smoking crack alone or cigarettes alone (p < 0.05).Conclusions: Use of crack increases intrapulmonary concentrations of iron and ferritin. Effects of crack on extracellular ferritin concentrations may be additive with effects of cigarette smoking. Although the mechanism(s) causing pulmonary iron accumulation were not identified by this study, it may be a result of occult alveolar hemorrhage or increased vascular permeability. The increase in lung iron burden in habitual crack users could promote chronic lung diseases in these subjects. [ABSTRACT FROM AUTHOR]

Background: Hyperglycemia is associated with adverse outcomes in patent with traumatic brain injury. There is convincing evidence of the deleterious effects of early systemic hyperglycemia on neurological outcomes and guides management toward intensive glycemic control. The purpose of this systematic review and meta analysis is to evaluate and summarize the level of evidence on the role of glycemic control in traumatic brain injury., Methods: A systematic review and meta-analysis were performed following PRISMA guidelines. This review involved studies conducted in humans covering glycemic control in traumatic brain injury. A systematic literature search was performed in PubMed, Embase, EBSCO Host, Scopus, ScienceDirect, Medline, and LILACS from database inception to October 2020. The risk of bias was evaluated with the GRADE quality Scale., Results: The results of this meta-analysis that involved 1236 patients included in 10 studies suggest that intensive glycemic control did not show significant differences in mortality compared with conservative management (RR 0.99 [95 % CI 0.81-1.21] p = 0.92). Intensive glycemic control reduced the risk of unfavorable clinical outcomes compared to standard management (RR 0.87 [95 % CI 0.78-0.96] p = 0.007) and increased favorable clinical outcomes compared to standard neurocritical care (RR 1.19 [95 % CI 1.02-138] p = 0.003)., Conclusions: The possible effect of glycemic control could be associated with silent hypoglycemic episodes during intensive care. Further studies evaluating the impact of glycemic control in traumatic brain injury are necessary., Competing Interests: Conflict of Interest The authors have no conflict of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose of Review: To evaluate the role of sedation vacations in optimizing patient outcomes and enhancing the quality of care in neurological intensive care units (ICUs). We discuss the importance of sedation management in neurocritical care, considering recent research findings and clinical guidelines., Recent Findings: Recent studies have highlighted the significance of sedation interruption protocols in improving patient outcomes in the ICU setting. Evidence suggests that daily sedation interruptions can reduce the duration of mechanical ventilation, ICU length of stay, and mortality rates. However, the implementation of these protocols requires careful consideration of patient-specific factors and a multidisciplinary approach. Sedation vacations play a critical role in neurocritical care by reducing mechanical ventilation duration, ICU stay length, and mortality rates. Despite the benefits, the presence of complications must be addressed to avoid adverse outcomes. Continued research is necessary to refine these strategies and improve guideline quality, ensuring safe and effective sedation management in critically ill neurological patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The use of cocaine can lead to a variety of neurologic complications, including cerebral vasoconstriction, ischemia, aneurysm formation, and aneurysm rupture. A previous study has shown that cocaine use is associated with an increased risk of subarachnoid hemorrhage (SAH). This study conducted a systematic review and meta-analysis of observational studies to assess the association between cocaine use and the risk of poor neurological outcomes and mortality in patients with SAH., Methods: A systematic review and meta-analysis were performed following the meta-analysis of observational studies in epidemiology (MOOSE) declaration for systematic reviews and the Cochrane Manual of Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials (RCTs), nonrandomized clinical trials, and prospective and retrospective cohort studies that reported data about adults who suffered Aneurysmal Subarachnoid Hemorrhage (aSAH) after having consumed cocaine recreationally were included. Variables such as mortality, vasospasm, seizures, re-bleeding, and complications were analyzed., Results: After a thorough selection process, 14 studies involving 116,141 patients, of which 2227 had a history of cocaine consumption, were included in the analysis. There was a significant increase in overall unfavorable outcomes in aSAH patients with a history of cocaine use (OR 5.51 CI 95% [4.26-7.13] P = <0.0001; I2 = 78%), with higher mortality and poor neurologic outcomes. There were no significant differences in the risk of hydrocephalus, seizures, or re-bleeding. Cocaine use was found to increase the risk of vasospasm and overall complications., Conclusions: This study insinuates that cocaine use is associated with worse clinical outcomes in aSAH patients. Despite the cocaine users did not exhibit a higher risk of certain complications such as hydrocephalus and seizures, they had an increased risk of vasospasm and overall complications. These findings highlight the importance of addressing the issue of cocaine consumption as a primary preventive measure to decrease the incidence of aSAH and improve patient outcomes., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objectives: D-dimer levels are increased in stroke and cancer. Cancer patients are at a higher risk of stroke. However, the evidence is unclear if high D-dimer in stroke patients can suggest the diagnosis of concomitant cancer or the development of stroke in a cancer patient. The objective is to assess the evidence available on the baseline D-dimer level in stroke patients with and without cancer., Materials and Methods: We conducted the systematic review and meta-analysis using the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We searched PUBMED, Cochrane, ScienceDirect, and Scopus for potentially eligible articles published till June 2023. All the review steps were iterative and done independently by two reviewers. The Newcastle-Ottawa scale tool was used to assess the quality of included studies for case control and cohort studies and the Agency for Healthcare Research and Quality tool for cross-sectional studies. The qualitative synthesis is presented narratively, and quantitative synthesis is shown in the forest plot using the random effects model. I 2 of more than 60% was considered as high heterogeneity., Results: The searches from all the databases yielded 495 articles. After the study selection process, six papers were found eligible for inclusion in the qualitative and quantitative synthesis. In the present systematic review, 2651 patients with ischemic infarcts are included of which 404 (13.97%) patients had active cancer while 2247 (86.02%) did not. The studies included were of high quality and low risk of bias. There were significantly higher baseline D-dimer levels in stroke patients with cancer than in non-cancer patients with a mean difference of 4.84 (3.07-6.60) P < 0.00001., Conclusion: D-dimer is a simple and relatively non-expensive biomarker that is increased to significant levels in stroke patients, who have cancer and therefore may be a tool to predict through screening for active or occult cancer in stroke patients., Competing Interests: There are no conflicts of interest., (© 2024 Published by Scientific Scholar on behalf of Journal of Neurosciences in Rural Practice.)

Glioblastoma (GBM) is an aggressive malignancy of the central nervous system (CNS) that remains incurable despite the multitude of improvements in cancer therapeutics. The conventional chemo and radiotherapy post-surgery have only been able to improve the prognosis slightly; however, the development of resistance and/or tumor recurrence is almost inevitable. There is a pressing need for adjuvant molecular therapies that can successfully and efficiently block tumor progression. During the last few decades, non-coding RNAs (ncRNAs) have emerged as key players in regulating various hallmarks of cancer including that of GBM. The levels of many ncRNAs are dysregulated in cancer, and ectopic modulation of their levels by delivering antagonists or overexpression constructs could serve as an attractive option for cancer therapy. The therapeutic potential of several types of ncRNAs, including miRNAs, lncRNAs, and circRNAs, has been validated in both in vitro and in vivo models of GBM. However, the delivery of these RNA-based therapeutics is highly challenging, especially to the tumors of the brain as the blood-brain barrier (BBB) poses as a major obstacle, among others. Also, since RNA is extremely fragile in nature, careful considerations must be met while designing a delivery agent. In this review we have shed light on how ncRNA therapy can overcome the limitations of its predecessor conventional therapy with an emphasis on smart nanomaterials that can aide in the safe and targeted delivery of nucleic acids to treat GBM. Additionally, critical gaps that currently exist for successful transition from viral to non-viral vector delivery systems have been identified. Finally, we have provided a perspective on the future directions, potential pathways, and target areas for achieving rapid clinical translation of, RNA-based macromolecular therapy to advance the effective treatment of GBM and other related diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Coenzyme-Q10 (CoQ10) is a hydrophobic benzoquinone with antioxidant and anti-inflammatory properties. It is known to reduce oxidative stress in various health conditions. However, due to the low solubility, permeability, stability, and poor oral bioavailability, the oral dose of CoQ10 required for the desired therapeutic effect is very high. In the present study, CoQ10 is encapsulated into two milk derived proteins β-lactoglobulin and lactoferrin (BLG and LF) to produce self-assembled nanostructures of around 100-300 nm with high encapsulation efficiency (5-10% w/w). Both CoQ10-BLG and CoQ10-LF nanoparticles (NPs) significantly improved the aqueous solubility of CoQ10 60-fold and 300-fold, compared to CoQ10 alone, which hardly dissolves in water. Insight into the difference in solubility enhancement between BLG and LF was obtained using in silico modeling, which predicted that LF possesses multiple prospective CoQ10 binding sites, potentially enabling greater loading of CoQ10 on LF compared to BLG, which was predicted to be less capable of binding CoQ10. At pH 7.4, CoQ10-LF NPs showed a burst release between 30 min and 2 h then plateaued at 12 h with 30% of the total drug released over 48 h. However, pure CoQ10-BLG and pure CoQ10 had a significantly lower release rate with less than 15% and 8% cumulative release in 48 h, respectively. Most importantly, both BLG and LF NPs significantly improved CoQ10 permeability compared to the pre-dissolved drug across the Caco-2 monolayer with up to 2.5-fold apparent permeability enhancement for CoQ10-LF─further confirming the utility of this nanoencapsulation approach. Finally, in murine macrophage cells (J774A.1), CoQ10-LF NPs displayed significantly higher anti-ROS properties compared to CoQ10 (predissolved in DMSO) without affecting the cell viability. This study paves the way in improving oral bioavailability of poorly soluble drugs and nutraceuticals using milk-based self-assembled nanoparticles.

Background: The supraorbital approach is a modification of the traditional pterional approach, and it offers the benefits of a shorter skin incision and a smaller craniotomy than the pterional approach. The purpose of this systemic review study was to compare the two surgical approaches for raptured and unruptured anterior cerebral circulation aneurysms., Methods: We searched PubMed, EMBASE, Cochrane Library, SCOPUS, and MEDLINE, up to August 2021, for published studies on the supraorbital vs pterional keyhole approach for anterior cerebral circulation aneurysms, and reviewers performed a brief qualitative descriptive analysis of both approaches., Results: Fourteen eligible studies were included in this systemic review. Results indicated that the supraorbital approach for anterior cerebral circulation aneurysms had fewer ischemic events compared to pterional approach. However, no significant difference between both groups in terms of complications such as intraoperative aneurysm rupture, brain hematoma, and postoperative infections for ruptured aneurysms., Conclusion: The meta-analysis suggests that the supraorbital method for clipping anterior cerebral circulation aneurysms might be a viable alternative to the traditional pterional method as the supraorbital group had decreased ischemic events compared to the pterional group, however, the associated difficulties in utilizing this approach among ruptured aneurysms with cerebral oedema and midline shifts further needs to be understood., (© 2023 The Authors.)

Introduction: The subarachnoid hemorrhage due to a ruptured brain aneurysm is a neurological emergency with high mobility and mortality. Hypertensive states are related to a bad prognosis and a higher risk of a ruptured aneurysm. However, the relationship between the blood pressure variability with the aneurysmal subarachnoid hemorrhage and its prognosis is quite unknown., Evidence Acquisition: A systematic review was performed across the databases. The following descriptors and related were used for the search: blood pressure, arterial pressure, variability, subarachnoid hemorrhage, hemorrhage, aneurysmal, aneurysmal subarachnoid hemorrhage. The following data were extracted: Glasgow Outcome Scale or Modified Rankin Scale, and blood pressure variabilities to categorize the prognosis., Evidence Synthesis: Five studies were selected. The blood pressure variability and the related outcome were assessed by mean systolic blood pressure and minimum systolic blood. The meta-analysis of mean systolic blood pressure (cut-off >95.3 mmHg) showed an odds ratio of 11.23 (95% CI: 4.423 to 28.537) (P≤0.001), predicting the good outcome after the aneurysmal subarachnoid hemorrhage. The pooled analysis revealed AUC of the ROC predicting the good outcome was statistically significant (AUC: 0.85, P<0.001). The pooled data analysis of minimum systolic blood pressure revealed an odds ratio of 6.43 (95% CI: 2.834-14.589, P<0.001) and AUC of the pooled ROC 0.931 (95% CI: 0.851 to 1.000, P<0.001) to predict poor outcome. The funnel plot through Egger's test for the analysis showed different grades of asymmetry., Conclusions: The blood pressure variability (mean and minimum systolic blood pressure) is a good predictor and parameter in the aneurysmal subarachnoid hemorrhage prognosis and outcome prediction.

Extracting information from the peripheral nervous system with implantable devices remains a significant challenge that limits the advancement of closed-loop neural prostheses. Linear electrode arrays can record neural signals with both temporal and spatial selectivity, and velocity selective recording using the delay-and-add algorithm can enable classification based on fibre type. The maximum likelihood estimation method also measures velocity and is frequently used in electromyography but has never been applied to electroneurography. Therefore, this study compares the two algorithms using in-vivo recordings of electrically evoked compound action potentials from the ulnar nerve of a pig. The performance of these algorithms was assessed using the velocity quality factor (Q-factor), computational time and the influence of the number of channels. The results show that the performance of both algorithms is significantly influenced by the number of channels in the recording array, with accuracies ranging from 77% with only two channels to 98% for 11 channels. Both algorithms were comparable in accuracy and Q-factor for all channels, with the delay-and-add having a slight advantage in the Q-factor.

Traumatic brain injury is caused by mechanical forces impacting the skull and its internal structures and constitutes one of the main causes of morbidity and mortality in the world. Clinically, severe traumatic brain injury is associated with the development of acute lung injury and so far, few studies have evaluated the cellular, molecular and immunological mechanisms involved in this pathophysiological process. Knowing and investigating these mechanisms allows us to correlate pulmonary injury as a predictor of cerebral hypoxia in traumatic brain injury and to use this finding in decision making during clinical practice. This review aims to provide evidence on the importance of the pathophysiology of traumatic brain injury-acute lung injury, and thus confirm its role as a predictor of cerebral hypoxia, helping to establish an appropriate therapeutic strategy to improve functional outcomes and reduce mortality.

This study aimed to develop synergistic therapies to treat superbug infections through the encapsulation of sortase A inhibitors (SrtAIs; trans -chalcone (TC), curcumin (CUR), quercetin (QC), or berberine chloride (BR)) into MCM-41 mesoporous silica nanoparticles (MSNs) or a phosphonate-modified analogue (MCM-41-PO 3 - ) to overcome their poor aqueous solubility. A resazurin-modified minimum inhibitory concentration (MIC) and checkerboard assays, to measure SrtAI synergy in combination with leading antimicrobial peptides (AMPs; pexiganan (PEX), indolicidin (INDO), and [I5, R8] mastoparan (MASTO)), were determined against methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus , Escherichia coli , and Pseudomonas aeruginosa . The results demonstrated that the MCM-41 and MCM-41-PO 3 - formulations significantly improved the aqueous solubility of each SrtAI. The MICs for SrtAI/MCM-41-PO 3 - formulations were lower compared to the SrtAI/MCM-41 formulations against tested bacterial strains, except for the cases of BR/MCM-41 and QC/MCM-41 against P. aeruginosa . Furthermore, the following combinations demonstrated synergy: PEX with TC/MCM-41 (against all strains) or TC/MCM-41-PO 3 - (against all strains except P. aeruginosa ); PEX with BR/MCM-41 or BR/MCM-41-PO 3 - (against MSSA and MRSA); INDO with QC/MCM-41 or QC/MCM-41-PO 3 - (against MRSA); and MASTO with CUR/MCM-41 (against E. coli ). These combinations also reduced each components' toxicity against human embryonic kidney cells. In conclusion, MCM-41 MSNs provide a platform to enhance SrtAI solubility and demonstrated antimicrobial synergy with AMPs and reduced toxicity, providing novel superbug treatment opportunities.

End-of-life care is an increasingly relevant topic due to advances in biomedical research and the establishment of new disciplines in evidence-based medicine and bioethics. Euthanasia and assisted suicide are two terms widely discussed in medicine, which cause displeasure on many occasions and cause relief on others. The evolution of these terms and the events associated with their study have allowed the evaluation of cases that have established useful definitions for the legal regulation of palliative care and public policies in the different health systems. However, there are still many aspects to be elucidated and defined. Based on the above, this review aimed to compile relevant historical aspects on the evolution of euthanasia and assisted suicide, which will allow understanding the use and research of these terms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: With the growing use of endovascular therapy (EVT) to manage unruptured intracranial aneurysms (IAs), detailed information regarding periprocedural complication rates of microsurgical clipping and EVT becomes increasingly important in determining the optimal treatment for individual cases. We report the complication rates associated with open microsurgery in a large series of unruptured IAs and highlight the importance of maintaining surgical skill in the EVT era., Methods: We reviewed all cases of unruptured IAs treated with open microsurgery by a single neurosurgeon between July 1997 and June 2019. We analyzed surgical complications, deaths, and patient-reported outcomes., Results: A total of 1923 unruptured IAs in 1750 patients (mean age 44 [range: 6-84], 62.0% [1085/1750] female) were treated surgically during the study period. Of the aneurysms treated, 84.9% (1632/1923) were small, 11.1% (213/1923) were large, and 4.1% (78/1923) were giant. Aneurysm locations included the middle cerebral artery (44.2% [850/1923]), internal carotid artery (29.1% [560/1923]), anterior cerebral artery (21.0% [404/1923]), and vertebrobasilar system (5.7% [109/1923]). The overall mortality rate was 0.3% (5/1750). Surgical complications occurred in 7.4% (129/1750) of patients, but only 0.4% (7/1750) experienced permanent disability. The majority of patients were able to return to their preoperative lifestyles with no modifications (95.9% [1678/1750])., Conclusions: At a high-volume, multidisciplinary center, open microsurgery in carefully selected patients with unruptured IAs yields favorable clinical outcomes with low complication rates. The improvement of EVT techniques and the ability to refer cases for EVT when a high complication rate with open microsurgery was expected have contributed to an overall decrease in surgical complication rates. These results may serve as a useful point of reference for physicians involved in treatment decision-making for patients with unruptured IAs., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The brain-lung interaction can seriously affect patients with traumatic brain injury, triggering a vicious cycle that worsens patient prognosis. Although the mechanisms of the interaction are not fully elucidated, several hypotheses, notably the "blast injury" theory or "double hit" model, have been proposed and constitute the basis of its development and progression. The brain and lungs strongly interact via complex pathways from the brain to the lungs but also from the lungs to the brain. The main pulmonary disorders that occur after brain injuries are neurogenic pulmonary edema, acute respiratory distress syndrome, and ventilator-associated pneumonia, and the principal brain disorders after lung injuries include brain hypoxia and intracranial hypertension. All of these conditions are key considerations for management therapies after traumatic brain injury and need exceptional case-by-case monitoring to avoid neurological or pulmonary complications. This review aims to describe the history, pathophysiology, risk factors, characteristics, and complications of brain-lung and lung-brain interactions and the impact of different old and recent modalities of treatment in the context of traumatic brain injury.

Flow diverters have become a critical instrument for complex aneurysms treatment. However, limited data are currently available regarding short and long-term outcomes for the Silk flow diverter. The objective of the study is to determine neurological prognosis and mortality rates for the Silk flow diversion device used in intracranial aneurysms. A systematic review with meta-analysis was performed using databases. The following descriptors were used for the search: "SILK", "Flow Diverter", "Mortality", and "Prognosis". The following data were extracted: mortality, good functional outcome, Glasgow outcome scale, complete or near-complete occlusion rates, rate of retreatment, and complications (thromboembolic and hemorrhagic complications). A total of 14 studies were selected. Among the 14 studies, 13 were retrospective observational cohort studies and 1 was a prospective observational cohort study. The mortality rate was 2.84%. The clinical good outcomes rate was 93.3%. The poor outcome rate was 6.6%. The overall thromboembolic complication rate was 6.06% (95% confidence interval [CI] 0.00-6.37, P=0.12, I2=3.13%). The total hemorrhagic complication rate was 1.62% (95% CI 0.00-5.34, P=0.28, I2=1.56%). The complete aneurysm occlusion rate was 80.4% (95% CI 8.65-9.38, P<0.0001, I2=9.09%). The Silk diverter device has a good safety and efficacy profile for treating intracranial aneurysms with high complete occlusion rates.

Objectives: Systematically review the medical literature for the impact of beta-blockers on mortality and functional capacity in patients who suffered severe traumatic brain injury., Data Sources: The search included MEDLINE, EMBASE, and Ovid Evidence-Based Medicine, clinical trial registries, and bibliographies., Study Selection: All articles that reported outcome in TBI patients treated with beta-blockers., Data Extraction: Publication year, number of patients, outcome and follow-up. We performed a meta-analysis for each variable for which there were sufficient data to estimate mean differences., Data Synthesis: 12 studies were included, which involved retrospectively and prospectively collected data on 14,057 patients. The treatment with beta-blockers was associated with a reduction in mortality in patients who were treated with beta-blockers compared to the control group (OR 0.40, 95% CI 0.30-0.54p = <0.00001), with acceptable heterogeneity between studies (I2 = 65% p = 0.00008). Beta-blocker therapy decreases the risk of negative neurological and functional outcomes (OR 0.59, 95% CI 0.38-0.92 p = <0.00001), a very high statistical heterogeneity between the included studies (I2 = 80% p = 0.00004), being able to influence the results. An increase in favorable neurological and functional outcomes is shown (OR 1.19, 95% CI 1.07-1.31 p = 0.001) with acceptable heterogeneity (I2 = 52% p = 0.08)., Conclusions: The beta-blockers therapy is associated with significantly improves outcome in patients with TBI. Treatment with beta-blockers in patients with TBI is a promising frontier in neurotrauma., Abbreviations: CI: confidence interval; BB: Beta-Blockers; OR = odds ratio; TBI: Traumatic Brain Injury SD: Standard deviation; SNS: Sympathetic nervous system.

Study design Literature review., Objectives: Describe the implications of post-COVID syndrome due to neurological sequelae including treatment and the differences that may exist between this group of patients and those who present these events not associated with COVID-19., Methods: A non-systematic review of the literature was carried out in PubMed and Science Direct databases, using the keywords "Post-acute COVID-19 syndrome"; "Neurological complications"; "Neurologic Manifestations" "COVID-19″ and "Rehabilitation", as well as synonyms, which were combined with the operators "AND" and "OR"., Results: The COVID-19 viral caustive agent, SARS-CoV-2, has a high affinity for human angiotensin-converting enzyme 2 receptor on type II pneumocytes. This receptor is also expressed in neurons and glial cells. Based on the foregoing and other not so clear mechanisms, it is stated that SARS-CoV-2 has tropism for the nervous system, being evident through the neurological manifestations observed in patients with mild, moderate and severe phenotype of the disease such as anosmia, ageusia, headache, cerebrovascular accidents, Guillain-Barré syndrome, seizures, and encephalopathy. This can generate severe sequelae and even fatal outcomes in those affected., Conclusions: Neurological complications caused by COVID-19 are frequent and represent a risk that compromises the functional capacity and the life of patients. The suspicion of these conditions, the strict control of metabolic alterations and cardiovascular risk factors, the effective and safe treatment of these entities, are a current challenge throughout the pandemic. The rehabilitation process in these patients is a challenge. This is due to the limitations generated by multi-organ damage, as well as risk of brain death., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Subarachnoid hemorrhage (SAH) continues to be a condition that carries high rates of morbidity, mortality, and disability around the world. One of its complications is neurogenic pulmonary edema (NPE), which is mainly caused by sympathetic hyperactivity. Due to the complexity of the pathophysiological process and the unspecificity of the clinical presentation, it is little known by general practitioners, medical students and other health care workers not directly related to the neurological part, making the management of this chaotic condition difficult. This review aims to present recent evidence on clinical concepts relevant to the identification and management of NPE secondary to SAH., Main Body of the Abstract: NPE is defined as a syndrome of acute onset following significant central nervous system (CNS) injury. Its etiology has been proposed to stem from the release of catecholamines that produce cardiopulmonary dysfunction, with this syndrome being associated with spinal cord injury, cerebrovascular disorders, traumatic brain injury, status epilepticus, and meningitis. NPE has long been considered a rare event; but it may occur more frequently, mainly in patients with SAH. There are two clinical presentations of NPE: the early form develops in the first hours/minutes after injury, while the late form presents 12-24 h after neurological injury. Clinical manifestations consist of non-specific signs of respiratory distress: dyspnea, tachypnea, hypoxia, pink expectoration, crackles on auscultation, which usually resolve within 24-48 h in 50% of patients. Unfortunately, there are no tools to make the specific diagnosis, so the diagnosis is by exclusion. The therapeutic approach consists of two interventions: treatment of the underlying neurological injury to reduce intracranial pressure and control sympathetic hyperactivity related to the lung injury, and supportive treatment for pulmonary edema., Short Conclusion: SAH is a severe condition that represents a risk to the life of the affected patient due to the possible complications that may develop. NPE is one of these complications, which due to the common manifestation of a respiratory syndrome, does not allow early and accurate diagnosis, being a diagnosis of exclusion. Therefore, in any case of CNS lesion with pulmonary involvement, NPE should be suspected immediately., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2021.)

Neurological complications from novel coronavirus is becoming more common. These patients usually have primary pulmonary problem of acute lung injury. Presentation in the form of encephalitis, meningitis, Guillain-Barre syndrome and seizures are noted. It is also noted that SARS-CoV-2 has predilection for brain stem leading to patient not feeling extensive pulmonary injury. Here we share another neurological presentation.

Purpose: To investigate the effectiveness of palliative pelvic radiation therapy (PRT) in patients with bladder cancer and identify factors associated with treatment outcome., Methods and Materials: Patients with bladder cancer receiving PRT were identified retrospectively from 2 cancer centers between 2014 and 2017. Patients were stratified by age, stage, performance status, comorbidities, previous chemotherapy, previous radiation therapy, and radiation therapy protocol. Patients were followed up at 6 weeks after radiation therapy (RT). Median overall survival (mOS) from the last fraction of RT was calculated. Death within 30 days of RT or noncompletion of treatment were considered as futile treatment., Results: Two hundred forty-one patients were identified as receiving PRT. A variety of RT protocols were used: 8 Gy in 1 fraction (11%), 21 Gy in 3 fractions (15%), 20 Gy in 5 fractions (18%), 36 Gy in 6 fractions (36%), and 27.5 to 30 Gy in 8 to 10 fractions (18%). Thirty-eight percent of patients were of poor performance status (Eastern Cooperative Oncology Group performance status ≥3), and 46.5% had significant comorbidities (Adult Comorbidity Evaluation-27 ≥2). The mOS from the last fraction of RT was 153 days (0-1289 days). The 30-day mortality after radiation therapy was 18% (n = 44), and the rate of incomplete planned radiation therapy treatment was 14% (n = 33). First follow-up information was available in 62% (n = 150) of patients. Median time to this follow-up was 49 days (14-238 days). At first follow-up at about 6 weeks after the last fraction of radiation therapy, symptoms were reported in 150 of 200 (75%) living patients; 80 of 150 (53%) patients reported improvement in symptoms after treatment. There were significant differences in mOS with stage, performance status, and comorbidities., Conclusions: One in 4 patients either did not complete the planned RT course or died within 30 days of treatment. These patients were unlikely to have received maximal benefit from treatment but may have experienced side effects, making treatment futile. Patients with good performance status and earlier stage disease survived longer. Patient selection and comprehensive assessment are crucial in selecting appropriate patients for treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Resveratrol (RES) is a naturally existing polyphenol which exhibits anti-oxidant, anti-inflammatory, and anti-cancer properties. In recent years, RES has attracted attention for its synergistic effect with other anti-cancer drugs for the treatment of drug resistant cancers. However, RES faces the issues of poor pharmacokinetics, stability and low solubility which limits its clinical application. In present study, RES has been loaded onto uniformly sized (~60 nm) mesoporous silica nanoparticles (MSNs) to improve its in vitro anti-proliferative activity and sensitization of Docatexal in hypoxia induced drug resistance in prostate cancer. RES was efficiently encapsulated within phosphonate (negatively charged) and amine (positively charged) modified MSNs. The effect of surface functionalization was studied on the loading, in vitro release, anti-proliferative and cytotoxic potential of RES using prostate cancer cell line. At pH 7.4 both free and NH 2 -MSNs loaded RES showed burst release which was plateaued with almost 90% of drug released in first 12 h. On the other hand, PO 3 -MSNs showed significantly slower release kinetics with only 50% drug release in first 12 h at pH 7.4. At pH 5.5, however, both the PO 3 -MSNs and NH 2 -MSNs showed significant control over release (around 40% less release compared with free RES in 24 h). Phosphonate modified MSNs significantly enhanced the anti-proliferative potential of RES with an IC 50 of 7.15 μM as compared to 14.86 μM of free RES whereas amine modified MSNs didn't affect proliferation with an IC 50 value higher than free RES (20.45 μM). Furthermore, RES loaded onto PO 3 -MSNs showed robust and dose dependent sensitization of Docatexal in hypoxic cell environment which was comparable to pure RES solution. This study provides an example of applicability of MSNs loaded with polyphenols such as RES as next generation anticancer formulations for treating drug resistant cancers such as prostate cancer., (Copyright © 2019 Chaudhary, Subramaniam, Khan, Abeer, Qu, Janjua, Kumeria, Batra and Popat.)

Background: The implementation of advanced healthcare directives, prepared by almost half of the adult population in United States remains relatively under studied. We determined the impact of advanced healthcare directives on treatment decisions by multiple physicians in stroke patients., Methods: A deidentified summary of clinical and radiological records of 28 patients with stroke was given to six stroke physicians who were not involved in the care of the patients. Each physician independently rated 28 treatment decisions per patient in the presence or absence of advanced healthcare directives 1 month apart to allow memory washout. The percentage agreement to treat/intervene per patient and proportion of treatment withheld as a group were estimated for each of the 28 treatment decision items. We also determined the interobserver reliability between the two raters (attorneys) in interpretation of six items characterizing the adequacy of documentation within the 28 advanced healthcare directives., Results: The percentage agreement among physician raters for treatment decisions in 28 stroke patients was highest for treatment of hyperpyrexia (100%, 100%) and lowest for ICU monitoring duration based on family-physician considerations outside of accepted criteria within institution (68%, 69%) in presence and absence of advanced healthcare directives. The physician rater agreement in choosing "yes" was highest for "routine-complexity" treatment decisions and lowest for "moderate-complexity" treatment decisions. The choice of withholding treatment in "routine-complexity," "moderate-complexity," or "high-complexity" treatment decisions was remarkably similar among raters in presence or absence of advanced healthcare directives. The only treatment decision that showed an impact of advanced healthcare directives was ICU monitoring withheld in 32% of treatment decisions in presence of directives (compared with 8% in the absence of directives). IV medication and defibrillation for cardiac arrest was withheld in 29% (compared with 19%) of the treatment decisions in the presence of advanced healthcare directives. The two attorney raters found the description of acceptable outcome inadequate in 14 and 21 of 28 advanced healthcare directives reviewed, respectively. The overall mean kappa for agreement regarding adequacy of documentation was modest (43%) for "does the advanced healthcare directive specify which treatments the patient would choose, or refuse to receive if they were diagnosed with an acute, terminal condition?" and lowest (3%) for "description of acceptable outcome.", Conclusions: We did not find any prominent differences in most "routine-complexity," "moderate-complexity," or "high-complexity" treatment decisions in patient management in the presence of advanced healthcare directives. Presence of advanced healthcare directives also did not reduce the prominent variance among physicians in treatment decisions.

Background: Bivalirudin is an ultrashort acting direct thrombin inhibitor, which has been used in place of heparin in selected settings. We describe our preliminary experience with the use of bivalirudin in patients who required anticoagulation for a deep vein thrombosis, prosthetic heart valve, or hypercoagulable state but were felt to be at high risk for the use of heparin., Methods: Eight patients in our neurocritical care unit required anticoagulation but were felt to be poor candidates for heparin either due to heparin-induced thrombocytopenia or due to high risk for intracranial hemorrhage. A standard protocol was utilized for bivalirudin with a loading dose of 0.75 mg/kg followed by a continuous infusion of 0.15 mg/kg hr. Serial aPTT levels were checked on a routine basis to monitor therapeutic effect. The bivalirudin infusion was continued for a period of 2 days to 2 weeks prior to starting coumadin therapy., Results: These patients were in the early postoperative period (within 48 h) following craniotomy, had suffered a recent large hemispheric infarct with hemorrhagic conversion, or had presented with an acute intracerebral hemorrhage. In this small series of patients, no intracranial hemorrhagic complications were encountered. No patients demonstrated progressive systemic thrombotic issues while on bivalirudin., Conclusion: Based on these findings, bivalirudin may represent a reasonable alternative in patients for whom heparin anticoagulation is contraindicated. A larger multicenter trial of bivalirudin in this setting may be appropriate.

Background: Cortical venous injury can occur during any intracranial procedure with potentially severe consequences. We describe a simple technique that allowed for successful repair of a large cortical draining vein., Case Description: A 43-year-old, right-handed woman presented with 6 months of headaches and progressive difficulty with right-sided hemiparesis. She had significant loss of hand coordination and writing ability. Computed tomography and MR imaging revealed a parasagittal meningioma in the left, posterior frontal region. The patient underwent craniotomy with resection of the lesion., Conclusion: When a cortical vein is injured, collateral drainage pathways may prevent the development of a clinical problem. Because of the unpredictability of these collateral channels, venous reconstruction may be feasible and even straightforward in some cases.

Object: The authors report the management protocol and successful outcomes in 6 patients with dissecting aneurysms of the posterior inferior cerebellar artery (PICA)., Methods: Medical records and neuroimaging studies of 6 patients who underwent surgical treatment of dissecting PICA aneurysms were reviewed. The mean follow-up duration was 1.8 years. No patient was lost to follow-up review., Results: Four patients presented with acute subarachnoid hemorrhage and 2 with PICA ischemia. All patients underwent surgery, which entailed proximal occlusion with distal revascularization in 3 cases and circumferential wrap/clip reconstruction in 3 cases. The revascularization techniques used were occipital artery-PICA bypass and PICA-PICA anastomosis. Delayed follow-up angiography was performed in all cases. In patients treated with proximal occlusion, delayed angiography showed minimal retrograde opacification of the dissected segments. The 3 patients treated with wrap/clip reconstruction showed unexpectedly significant normalization of their lesions on angiographic studies. Outcome was good in all cases., Conclusions: Dissecting PICA aneurysms are rare lesions with an apparent propensity for bleeding. Individualized management including distal revascularization with PICA sacrifice or circumferential wrap/clip reconstruction to reinforce the dissected segment produced good outcomes. Patients treated with aneurysm wrapping may show dramatic angiographic improvement of the dissected segment.

It is common practice to forcibly awaken patients from an all-night polysomnographic study prior to performance of a multiple sleep latency test (MSLT); either for reasons of protocol or for the convenience of the laboratory personnel. We report a case of a young woman who, by formal sleep study criteria, received the erroneous diagnosis of narcolepsy due to the effects of severe sleep deprivation, and document that the effects of prior sleep deprivation require more than one night of ad libitum sleep. Forced awakening prior to MSLT may permit sleep deprivation or delayed sleep phase syndrome to masquerade as narcolepsy or idiopathic central nervous system (CNS) hypersomnia.

Sleepiness impairs memory and concentration. We report a case of a patient who inadvertently left his infant son in a car, having forgotten to drop him off at day care. The infant died of heat exposure. There is credible evidence that sleepiness from a combination of sleep deprivation and previously undiagnosed severe obstructive sleep apnea contributed to this tragedy.