Foleycorbett2320

Sanguinate, a bovine PEGylated carboxyhemoglobin-based oxygen carrier with vasodilatory, oncotic and anti-inflammatory properties designed to release oxygen in hypoxic tissue, was tested to determine if it improves infarct volume, collateral recruitment and blood flow to the ischemic core in hyperacute middle cerebral artery occlusion (MCAO).

Under an IACUC approved protocol, 14 mongrel dogs underwent endovascular permanent MCAO. Seven received Sanguinate (8 mL/kg) intravenously over 10 min starting 30 min following MCAO and seven received a similar volume of normal saline. Relative cerebral blood flow (rCBF) was assessed using neutron-activated microspheres prior to MCAO, 30 min following MCAO and 30 min following intervention. Pial collateral recruitment was scored and measured by arterial arrival time (AAT) immediately prior to post-MCAO microsphere injection. Diffusion-weighted 3T MRI was used to assess infarct volume approximately 2 hours after MCAO.

Mean infarct volumes for control and Sanguinate-treated subjects were 4739 mm

and 2585 mm

(p=0.0443; r

=0.687), respectively. Following intervention, rCBF values were 0.340 for controls and 0.715 in the Sanguinate group (r

=0.536; p=0.0064). Pial collateral scores improved only in Sanguinate-treated subjects and AAT decreased by a mean of 0.314 s in treated subjects and increased by a mean of 0.438 s in controls (p<0.0276).

Preliminary results indicate that topload bolus administration of Sanguinate in hyperacute ischemic stroke significantly improves infarct volume, pial collateral recruitment and CBF in experimental MCAO immediately following its administration.

Preliminary results indicate that topload bolus administration of Sanguinate in hyperacute ischemic stroke significantly improves infarct volume, pial collateral recruitment and CBF in experimental MCAO immediately following its administration.

We describe the first-in-human experience using the Route 92 Medical Aspiration System to perform thrombectomy in the initial 45 consecutive stroke patients enrolled in the SUMMIT NZ trial. This aspiration system includes a specifically designed delivery catheter which enables delivery of 0.070 inch and 0.088 inch aspiration catheters.

The SUMMIT NZ trial is a prospective, multicenter, single-arm study with core lab imaging adjudication. Patients presenting with acute ischemic stroke from large vessel occlusion are eligible to enrol. The study has had three phases which transitioned from use of the 0.070 inch to the 0.088 inch catheter.

Vessel occlusions were located in the internal carotid artery (27%), M1 (60%) and M2 (13%). Median baseline National Institutes of Health Stroke Scale (NIHSS) was 16 (IQR 10). Across the three phases, the first-pass reperfusion rate of modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b was 62% using the Route 92 Medical system; this rate was 29% in phase 1, 56% in phase 2, and 80% in phase 3. The first-pass reperfusion rate of mTICI ≥2c was 42% overall, 29% in phase 1, 33% in phase 2, and 55% in phase 3. A final reperfusion rate of mTICI ≥2b was achieved in 96% of cases, with 36% of cases using adjunctive devices. Patients had an average improvement of 6.7 points in NIHSS from baseline at 24 hours, and at 90 days 48% were functionally independent (modified Rankin Scale 0-2).

In this early experience, the Route 92 Medical Aspiration System has been effective and safe. The system has design features that improve catheter deliverability and have the potential to increase first-pass reperfusion rates in aspiration thrombectomy.

In this early experience, the Route 92 Medical Aspiration System has been effective and safe. The system has design features that improve catheter deliverability and have the potential to increase first-pass reperfusion rates in aspiration thrombectomy.In this paper, we first classify different types of second opinions and evaluate the ethical and epistemological implications of providing those in a clinical context. Second, we discuss the issue of how artificial intelligent (AI) could replace the human cognitive labour of providing such second opinion and find that several AI reach the levels of accuracy and efficiency needed to clarify their use an urgent ethical issue. Third, we outline the normative conditions of how AI may be used as second opinion in clinical processes, weighing the benefits of its efficiency against concerns of responsibility attribution. Fourth, we provide a 'rule of disagreement' that fulfils these conditions while retaining some of the benefits of expanding the use of AI-based decision support systems (AI-DSS) in clinical contexts. This is because the rule of disagreement proposes to use AI as much as possible, but retain the ability to use human second opinions to resolve disagreements between AI and physician-in-charge. Fifth, we discuss some counterarguments.

Delay to reperfusion in ST-elevation myocardial infarction (STEMI) is detrimental, but can be minimised with prehospital notification by ambulance to the treating hospital. We aimed to assess whether prenotification was associated with improved first medical contact to balloon times (FMC-BT) and whether this resulted in better clinical outcomes. We also aimed to identify factors associated with use of prenotification.

This was a retrospective study of prospective Victorian Cardiac Outcomes Registry data for patients undergoing primary percutaneous coronary intervention for STEMI from 2013-2018. Postcardiac arrest were excluded. Patients were grouped by whether they arrived by ambulance with prenotification (group 1), arrived by ambulance without prenotification (group 2) or self-presented (group 3). We compared groups by FMC-BT, incidence of major adverse cardiac and cerebrovascular events (MACCE), mortality and factors associated with the use of prenotification.

2891 patients were in group 1 (79.3% malended for fastest STEMI treatment.

Differences in clinical characteristics, particularly gender, time of presentation and culprit vessel may influence ambulance prenotification. Ambulance cohorts have high-risk features and worse outcomes compared with self-presenters. Improving system inequality in prehospital STEMI diagnosis is recommended for fastest STEMI treatment.

This study explored the perspectives and behaviours of emergency physicians (EPs), regularly involved in resuscitation, to identify the sources and effects of any stress experienced during a resuscitation as well as the strategies employed to deal with these stressors.

This was a two-centre sequential exploratory mixed-methods study of EPs consisting of a focus group, exploring the human factors related to resuscitation, and an anonymous survey. Between April and June 2020, the online survey was distributed to all EPs working at Australia's largest two major trauma centres, both in Melbourne, and investigated sources of stress during resuscitation, impact of stress on performance, mitigation strategies used, impact of the COVID-19 pandemic on stress and stress management training received. Associations with gender and years of clinical practice were also examined.

7 EPs took part in the focus group and 82 responses to the online survey were received (81% response rate). The most common sources of stresss well as the strategies that EPs use to mitigate the effects of stress on their performance. These findings may contribute to the development of tailored stress management training for critical care clinicians.

Stress is commonly experienced by EPs during resuscitation and can impact decision-making and procedural performance. This study identifies the most common sources of stress during a resuscitation as well as the strategies that EPs use to mitigate the effects of stress on their performance. These findings may contribute to the development of tailored stress management training for critical care clinicians.

Hyperbaric oxygen (HBO

) therapy has been proposed to treat hypoxaemia and reduce inflammation in COVID-19. Our objective was to analyse safety and efficacy of HBO

in treatment of hypoxaemia in patients with COVID-19 and evaluate time to hypoxaemia correction.

This was a multicentre, open-label randomised controlled trial conducted in Buenos Aires, Argentina, between July and November 2020. Patients with COVID-19 and severe hypoxaemia (SpO

≤90% despite oxygen supplementation) were assigned to receive either HBO

treatment or the standard treatment for respiratory symptoms for 7 days. HBO

treatment was planned for ≥5 sessions (1 /day) for 90 min at 1.45 atmosphere absolute (ATA). Outcomes were time to normalise oxygen requirement to SpO

≥93%, need for mechanical respiratory assistance, development of acute respiratory distress syndrome and mortality within 30 days. A sample size of 80 patients was estimated, with a planned interim analysis after determining outcomes on 50% of patients.

The trial was stopped after the interim analysis. 40 patients were randomised, 20 in each group, age was 55.2±9.2 years. At admission, frequent symptoms were dyspnoea, fever and odynophagia; SpO

was 85.1%±4.3% for the whole group. Patients in the treatment group received an average of 6.2±1.2 HBO

sessions. Time to correct hypoxaemia was shorter in treatment group versus control group; median 3 days (IQR 1.0-4.5) versus median 9 days (IQR 5.5-12.5), respectively (p<0.010). OR for recovery from hypoxaemia in the HBO

group at day 3 compared with the control group was 23.2 (95% CI 1.6 to 329.6; p=0.001) Treatment had no statistically significant effect on acute respiratory distress syndrome, mechanical ventilation or death within 30 days after admission.

Our findings support the safety and efficacy of HBO

in the treatment of COVID-19 and severe hypoxaemia.

NCT04477954.

NCT04477954.Therapeutic outcomes achieved in head and neck squamous cell carcinoma (HNSCC) patients by concurrent cisplatin-based chemoradiotherapy initially reflect both tumor regression and tumor stasis. However, local and distant metastasis and disease relapse are common in HNSCC patients. In the current work, we demonstrate that cisplatin treatment induces senescence in both p53 wild-type HN30 and p53 mutant HN12 head and neck cancer models. We also show that tumor cells can escape from senescence both in vitro and in vivo. We further establish the effectiveness of the senolytic, ABT-263 (Navitoclax), in elimination of senescent tumor cells after cisplatin treatment. Navitoclax increased apoptosis by 3.3-fold (P ≤ 0.05) at day 7 compared with monotherapy by cisplatin. Additionally, we show that ABT-263 interferes with the interaction between B-cell lymphoma-x large (BCL-XL) and BAX, anti- and pro-apoptotic proteins, respectively, followed by BAX activation, suggesting that ABT-263-induced apoptotic cell death is mediated through BAX. Our in vivo studies also confirm senescence induction in tumor cells by cisplatin, and the promotion of apoptosis coupled with a significant delay of tumor growth after sequential treatment with ABT-263. Sequential treatment with cisplatin followed by ABT-263 extended the humane endpoint to ∼130 days compared with cisplatin alone, where mice survived ∼75 days. learn more These results support the premise that senolytic agents could be used to eliminate residual senescent tumor cells after chemotherapy and thereby potentially delay disease recurrence in head and neck cancer patients. SIGNIFICANCE STATEMENT Disease recurrence is the most common cause of death in head and neck cancer patients. B-cell lymphoma-x large inhibitors such as ABT-263 (Navitoclax) have the capacity to be used in combination with cisplatin in head and neck cancer patients to eliminate senescent cells and possibly prevent disease relapse.