Gas Therapies for Neuro-Protection.

Objective The threat of hearing loss has become a universal reality. Gentamycin (GM) can lead to ototoxicity and may result in permanent hearing loss. This study aimed to elucidate whether the hypolipidemic drug Ezetimibe (EZE) has a possible underlying mechanism for protecting rats from GM-induced ototoxicity. Methods and results 30 male Wister albino rats were separated into three groups, ten in each group: control, GM, and GM + EZE. At the end of the experiment, rats underwent hearing threshold evaluation via auditory brainstem response (ABR), carotid artery blood flow velocity (CBV), and resistance (CVR) measurement, in addition to a biochemical assessment of serum malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), hemeOxygenase-1 (HO-1), and tumor necrosis factor-α (TNF-α). Also, real-time PCR was employed to quantify the levels of brain-derived neurotrophic factor (BDNF). Cochlea was also studied via histological and immunohistochemical methods. GM revealed a significant increase in CVR, MDA, NO, and TNF-α and a significant decrease in ABR, CBV, CAT, HO-1, and cochlear BDNF expression. EZE supplementation revealed a significant rise in ARB in addition to CBV and a decline in CVR and protected cochlear tissues via antioxidant, anti-inflammatory, and antiapoptotic mechanisms via downregulating Caspase-3 immunoreaction, upregulating proliferating cellular nuclear antigen (PCNA) immunoreaction, and upregulating of the cochlear BDNF expression. Correlations were significantly negative between BDNF and MDA, NO, TNF-α, COX 2, and caspase-3 immunoreaction and significantly positive with CAT, HO-1, and PCNA immunoreaction. Discussion EZE can safeguard inner ear tissues from GM via antioxidant, anti-inflammatory, and antiapoptotic mechanisms, as well as upregulation of BDNF mechanisms.

The medical on-site treatment of hypothermia: ICAR-MEDCOM recommendation.

The Post-resuscitative and initial Utility in Life Saving Efforts (PULSE) Conference represented an initiative by leaders of the international scientific community who sought opportunities for major improvements in clinical outcomes after cardiopulmonary resuscitation and after resuscitation from serious traumatic injury.1 The experts focused on scientific research that would yield major advances in lifesaving care, including measurable increases in survival and functional recovery. However, unless research support is prioritized to address resuscitation, it is highly unlikely that these opportunities would soon be realized. We lose more than 1000 lives each day in the United States from sudden, unexpected death, a fatality rate comparable to the crash of two 747 aircraft without survivors.2–5⇓⇓⇓ Cardiovascular disease is the leading cause of death among individuals aged greater than 65 years, the second leading cause of death among individuals aged 45 to 65 years, and the 5th leading cause of death among individuals aged 1 to 9 years.4,5⇓ Traumatic injuries in the United States were responsible for 147 891 deaths and 2.6 million hospitalizations, costing over $335 000 per death and resulting in 37 million emergency department visits in 1995.6,7⇓ Trauma is the leading cause of death among children and all individuals to age 34 years, the leading cause of loss of productive life-years of any disease, with societal costs (estimated by the National Safety Council) of $469 billion dollars annually, and the third leading cause of death among individuals aged 35 to 54 years. The Conferees anticipated that the availability of new intervention strategies with more effective diagnostic methodologies in the early post-injury time interval would not only save lives but also reduce morbidity.1 Accordingly, the PULSE participants cited current restraints and/or barriers to the delivery of more effective resuscitation interventions and reaffirmed that …

Aims: To investigate the hepatoprotective effects of red raspberry (Rubus idaeus L.) leaves against oxidative stress, inflammation and apoptosis induced by carbon tetrachloride (CCl4) in rats. Study Design and Methodology: Forty rats were divided into 5 groups, 1) normal control; 2) Raspberry (Rsp) control (100 mg/kg); 3) CCl4 control; 4) and 5) CCl4 groups pre-treated with 50 and 100 mg/kg of Rsp leaves, respectively, once daily for 10 days. Liver injury was induced on the 11th day in groups 3, 4 and 5 by intraperitoneal injection of CCl4 (1.0 ml/kg) in 50% olive oil (1:1). Serum and liver were separated and prepared for biochemical and histological assay. Antioxidant, inflammatory and apoptotic markers were evaluated. Results: CCl4-induced liver damage was manifested by increased activities of serum marker enzymes, elevated levels of lipid peroxidation and by decreased hepatic antioxidants including reduced glutathione, glutathione peroxidase, superoxide dismutase and catalase. CCl4 also resulted in elevated levels of hepatic inflammatory mediators including tumor necrosis factor-α (TNFα), interleukin -6 (IL-6), IL-1β and nitric oxide (NO) as well as upregulation of apoptotic markers including caspase-3, FasL and Bax. Hepatic levels of Bcl2, an anti-apoptotic factor, was Original Research Article Attia; EJMP, 14(1): 1-16, 2016; Article no.EJMP.25300 2 decreased by CCl4. Pretreatment with Rsp leaves significantly ameliorated the elevation in serum liver enzymes and prevented lipid peroxidation and the depletion of the antioxidants. In addition, Rsp leaves exhibited anti-inflammatory effects via attenuation of increased hepatic levels of TNF-α, Il-6, IL-1β and NO. Additionally, CCl4-Induced apoptosis in the liver cell was attenuated by Rsp pretreatment. With regard to histological examination, Rsp leaves significantly alleviated degeneration and necrosis of hepatocytes, accompanied by decreased inflammatory cell infiltration. Conclusion: These results suggest that Rsp leaves have protective effects against CCl4-induced acute liver injury, and this protection is likely due to antioxidant, anti-inflammatory and antiapoptotic mechanisms.

10647 Background: The initial treatment for early operable primary breast cancer (PBC) is surgery. Primary endocrine therapy with tamoxifen has been used in the elderly with estrogen receptor positive (ER+) PBC who refuse or are unfit for surgery. Current randomized data showed superiority of aromatase inhibitors (AIs) over tamoxifen in neoadjuvant, adjuvant and metastatic settings, it is possible that AIs may be a better therapeutic option in this context. We report the early clinical and biological data in using primary anastrozole for ER+ operable PBC in the elderly. Methods: Elderly (> 70) patients with ER+ early operable PBC (< 5cm), who refused or were unfit for surgery, and who had contraindications to tamoxifen, were treated with anastrozole 1mg daily as primary endocrine therapy. All had disease assessable by UICC criteria and received treatment for ≥ 6 months unless they progressed prior. Standard immunohistochemical staining was performed on tumor tissue, obtained by core biopsy, for ER, progesterone receptor (PgR) and HER2. Positivity for ER and PgR was defined by H-score ≥ 50, and HER2 positivity was defined as 3+. Results: Thirty-two patients received anastrozole as described during a two-year period. Thirty (93.8%) patients reached clinical benefit (CB = objective response (OR) + durable stable disease) at 6 months, with 11 (34.4%) ORs (complete response + partial response). Anastrozole was well tolerated with no patients withdrawn due to side effects. All patients had ER+ tumors. The response status at 6 months is stratified according to PgR and HER2 is shown in the table . Conclusions: Early clinical data has shown excellent efficacy and tolerability of anastrozole as primary endocrine therapy for early operable PBC in the elderly. The PgR and HER2 status did not appear to predict response within this group of ER+ tumors, but there was a trend towards a better quality of response (more ORs) for PgR positive/ HER2 negative tumors. Follow-up for longer-term efficacy assessment is continuing. [Table: see text] [Table: see text]

Background: Formal prognostication should be delayed at least 72 hours after cardiac arrest, but early stratification of risk severity provides important information for medical decision making, research enrollment, and precision medicine. Hypothesis: EEG-derived indices are valid biomarkers of severity of injury after cardiac arrest and contribute to early identification of risk. Aims: To assess the relative impact of early clinical data and processed EEG indices in the first 6 hours after recovery of spontaneous circulation (ROSC). Methods: Data from the first 6 hours after ROSC in the International Cardiac Arrest Registry (INTCAR) from Maine Medical Center including demographics, cardiac arrest data, admission vital signs and laboratory results and processed EEG indices at 6 hours after ROSC (bispectral index or BIS6 and suppression ratio or SR6) were extracted. Cerebral Performance Category (CPC) scores at hospital discharge and 6-month follow-up were dichotomized into good (CPC = 1-2) and poor (CPC = 3-5) outcomes. Three models were trained, one with INTCAR data, a second with EEG data, and the third combining INTCAR and BIS6-SR6. Six machine learning algorithms were applied: Catboost, random forest, Xgboost, Adaboost, support vector machine and logistic regression. Variable importance was analyzed by the decrease of impurity of random forest. Results: Among 913 included patients, median age was 59 years (95%CI 23-85), 623 (68%) were male, initial rhythm was shockable in 405 (44%) patients, and average time to ROSC was 23 (95%CI 3 - 73) minutes. Survival to hospital discharge occurred in 41% (364/893), and poor outcome occurred in 72.7% at 6-month follow-up (607/835). For CPC at discharge, area-under-the curve (AUC) was 0.85 for the combined INTCAR and EEG data, greater than INTCAR (AUC = 0.80) or EEG (AUC = 0.77). For the CPC at follow-up, the AUC was 0.88 for the combined data, greater than INTCAR (AUC = 0.83) or EEG (AUC = 0.79). Variable ranking analysis showed that BIS6 and SR6 were the two most informative features for both outcomes. Conclusions: The processed EEG variables BIS6 and SR6 significantly contribute to risk identification in the first 6 hours after ROSC, and combined with early clinical data provide reliable risk stratification.

Background: Inappropriate early neuroprognostication of out-of-hospital cardiac arrest (OHCA) patients may lead to inappropriate early withdrawal of life-sustaining treatments. Several prediction models using early clinical data have been published, with varying degrees of external validation. Hypothesis: Out of six commonly used clinical predictive models, at least one may have an acceptable specificity and negative predictive value and can be used to identify patients who will have poor neurological outcome and mortality. Aims: The aim of this study was to perform an external validation of six different clinical predictive models—the Cardiac Arrest Hospital Prognosis score (CAHP), Swedish Cardiac Arrest Risk Score, Targeted Temperature Management score, Out of Hospital Cardiac Arrest score, Miracle2 score, and the Cardiac Arrest Survival Score—to determine which scores accurately predict neurological outcome and survival. Methods: Data were collected on OHCA patients who were part of the International Cardiac Arrest Registry (INTCAR) and received treatment at Maine Medical Center between 2021 and 2023. Data from INTCAR and the electronic medical record were used to calculate predicted outcomes with specificity and negative predictive value used to determine if the models were externally valid. Statistical software was used to recreate the formulas for each model and Delong’s test was also performed in order to compare the discriminatory ability between models. Results: 222 patients were included with 91 (41%) having a shockable initial heart rhythm and a mean time to return of spontaneous circulation of 28.73 minutes (± 16.48); 75 (34%) patients survived to hospital discharge. Variability in discrimination was observed with AUC values ranging from 67.3 to 77.4. Among the models studied, the CAHP score resulted in the highest specificity (82.3), indicating an increased ability to correctly identify individuals with poor outcomes. This model was less likely to incorrectly categorize poor outcomes, with a false negative value of 51.4%. The OHCA model had the highest AUC value (77.4% [CI 70.6%-84.2%]). The Miracle2 score exhibited the best discrimination, allowing it to maintain greater consistency across all thresholds. Conclusions: While some prediction models have undergone external validation to determine their accuracy, the results from the patient population used in this study indicate that all models may lead to errors when predicting patient outcome.

Interim Guidance for Emergency Medical Services Management of Out-of-Hospital Cardiac Arrest During the COVID-19 Pandemic.

Pressure-synchronized cineangiography during experimental cardiopulmonary resuscitation.

Part 8 : Advanced life support : 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

Out-of-hospital cardiac arrest (OHCA) is a common initial presentation of cardiovascular disease, affecting up to 325 000 people in the United States each year.1 In a recent meta-analysis of >140 000 patients with OHCA, survival to hospital admission was 23.8%, and survival to hospital discharge was only 7.6%.2 In patients who initially achieve return of spontaneous circulation (ROSC) after OHCA, the significant subsequent morbidity and mortality are due largely to the cerebral and cardiac dysfunction that accompanies prolonged whole-body ischemia. This syndrome, called the post cardiac arrest syndrome, comprises anoxic brain injury, post cardiac arrest myocardial dysfunction, systemic ischemia/reperfusion response, and persistent precipitating pathology3,4 (Table 1). The contribution of each of these components in an individual patient depends on various factors, including prearrest comorbidities, duration of the ischemic insult, and cause of the cardiac arrest. This review focuses on therapeutic strategies and recent developments in managing patients who are initially resuscitated from cardiac arrest. View this table: Table 1. Post Cardiac Arrest Syndrome: Pathophysiology and Potential Treatment Strategies There are 3 major aspects that require consideration in the management of the post cardiac arrest patient. After resuscitation, a decision must be made in relation to the appropriate triage of the OHCA patient. The next phase of management concerns the in-hospital treatment, which must address each component of the postarrest syndrome as appropriate for the individual patient. Finally, there are issues relating to prognostication and the deployment of various secondary prevention measures. Our recommended treatment algorithm is summarized in the Figure. This ideally follows from the implementation of basic and advanced life support measures, including effective cardiopulmonary resuscitation and defibrillation when appropriate, which are major determinants of outcome.2 Such an approach to care may be further modified according to the presence of other comorbidities and precipitating factors, which should be assessed …

Using specific cytotoxics with a targeted mind

Despite recent advances in the management of post–cardiac arrest syndrome (PCAS), the survival rate, without neurologic sequelae after resuscitation, remains very low. Whole-body ischemia, followed by reperfusion after cardiac arrest (CA), contributes to PCAS, for which established pharmaceutical interventions are still lacking. It has been shown that a number of different processes can ultimately lead to neuronal injury and cell death in the pathology of PCAS, including vasoconstriction, protein modification, impaired mitochondrial respiration, cell death signaling, inflammation, and excessive oxidative stress. Recently, the pathophysiological effects of inhaled gases including nitric oxide (NO), molecular hydrogen (H2), and xenon (Xe) have attracted much attention. Herein, we summarize recent literature on the application of NO, H2, and Xe for treating PCAS. Recent basic and clinical research has shown that these gases have cytoprotective effects against PCAS. Nevertheless, there are likely differences in the mechanisms by which these gases modulate reperfusion injury after CA. Further preclinical and clinical studies examining the combinations of standard post-CA care and inhaled gas treatment to prevent ischemia–reperfusion injury are warranted to improve outcomes in patients who are being failed by our current therapies.

Part 1: Introduction

A Proposal for the Classification of Etiologies of Neurologic Deterioration after Acute Ischemic Stroke