The Role of the Glycocalyx in the Pathophysiology of Subarachnoid Hemorrhage-Induced Delayed Cerebral Ischemia

The glycocalyx is an important constituent of blood vessels located between the bloodstream and the endothelium. It plays a pivotal role in intercellular interactions in neuroinflammation, reduction of vascular oxidative stress, and provides a barrier regulating vascular permeability. In the brain, the glycocalyx is closely related to functions of the blood-brain barrier and neurovascular unit, both responsible for adequate neurovascular responses to potential threats to cerebral homeostasis. An aneurysmal subarachnoid hemorrhage (aSAH) occurs following rupture of an intracranial aneurysm and leads to immediate brain damage (early brain injury). In some cases, this can result in secondary brain damage, also known as delayed cerebral ischemia (DCI). DCI is a life-threatening condition that affects up to 30% of all aSAH patients. As such, it is associated with substantial societal and healthcare-related costs. Causes of DCI are multifactorial and thought to involve neuroinflammation, oxidative stress, neuroinflammation, thrombosis, and neurovascular uncoupling. To date, prediction of DCI is limited, and preventive and effective treatment strategies of DCI are scarce. There is increasing evidence that the glycocalyx is disrupted following an aSAH, and that glycocalyx disruption could precipitate or aggravate DCI. This review explores the potential role of the glycocalyx in the pathophysiological mechanisms contributing to DCI following aSAH. Understanding the role of the glycocalyx in DCI could advance the development of improved methods to predict DCI or identify patients at risk for DCI. This knowledge may also alter the methods and timing of preventive and treatment strategies of DCI. To this end, we review the potential and limitations of methods currently used to evaluate the glycocalyx, and strategies to restore or prevent glycocalyx shedding.Peer reviewe

Affordability impacts therapeutic intensity of acute management of severe traumatic brain injury patients:An exploratory study in Tanzania

Introduction: Quality health care in low and middle-income countries (LMICs) is constrained by financing of care. Research question: What is the effect of ability to pay on critical care management of patients with severe traumatic brain injury (sTBI)? Material and Methods: Data on sTBI patients admitted to a tertiary referral hospital in Dar-es-Salaam, Tanzania, were collected between 2016 and 2018, and included payor mechanisms for hospitalization costs. Patients were grouped as those who could afford care and those who were unable to pay. Results: Sixty-seven patients with sTBI were included. Of those enrolled, 44 (65.7%) were able to pay and 15 (22.3%) were unable to pay costs of care upfront. Eight (11.9%) patients did not have a documented source of payment (unknown identity or excluded from further analysis). Overall mechanical ventilation rates were 81% (n=36) in the affordable group and 100% (n=15) in the unaffordable group (p=0.08). Computed tomography (CT) rates were 71.6% (n=48) overall, 100% (n=44) and 0% respectively (p<0.01); Surgical rates were 16.4% (n=11) overall, 18.2% (n=8) vs. 13.3% (n=2) (p=0.67) respectively. Two-week mortality was 59.7% overall (n=40), 47.7% (n=21) in the affordable group and 73.3% (n=11) in the unaffordable group (p=0.09) (adjusted OR 0.4; 95% CI: 0.07-2.41, p=0.32). Discussion and Conclusion: Ability to pay appears to have a strong association with the use of head CT and a weak association with mechanical ventilation in the management of sTBI. Inability to pay increases redundant or sub-optimal care, and imposes a financial burden on patients and their relatives

Endovascular treatment and neurosurgical clipping in subarachnoid hemorrhage: a systematic review of economic evaluations

INTRODUCTION: There are two treatment modalities for aneurysmal subarachnoid hemorrhage: endovascular treatment and neurosurgical clipping. Results of economic evaluations are needed to gain insight into the relationship between clinical effectiveness and costs of these treatment modalities. This important information can inform both clinical decision-making processes and policymakers in facilitating Value-Based Healthcare. EVIDENCE ACQUISITION: Databases (PubMed, Embase, Cochrane Library, the Centre for Reviews and Dissemination, EBSCO, and Web of Science) were searched for studies published until October 2020 that had performed economic evaluations in aneurysmal subarachnoid hemorrhage patients by comparing endovascular treatment with neurosurgical clipping. The quality of reporting and methodology of these evaluations was assessed using the associated instruments (i.e. CHEERS statement and CHEC-list, respectively). EVIDENCE SYNTHESIS: A total of six studies met the inclusion criteria. All included studies reported both effects and costs, however five did not relate effects to costs. Only one study related effects directly to costs, thus conducted a full economic evaluation. The reporting quality scored 81% and the methodological quality scored 30%. CONCLUSIONS: The quality of published cost-effectiveness studies on the treatment of aneurysmal subarachnoid hemorrhage is poor. Six studies reported both outcomes and costs, however only one study performed a full economic evaluation comparing endovascular treatment to neurosurgical clipping. Although the reporting quality was sufficient, the methodological quality was poor. Further research that relates health-related quality of life measures to costs of endovascular treatment and neurosurgical clipping is required-specifically focusing on both reporting and methodological quality. Different subgroup analyses and modeling could also enhance the findings

Safety, tolerability, and clinical outcomes of hydroxychloroquine for hospitalized patients with coronavirus 2019 disease.

BackgroundSevere acute respiratory coronavirus 2 (SARS-CoV-2) has caused a devastating worldwide pandemic. Hydroxychloroquine (HCQ) has in vitro activity against SARS-CoV-2, but clinical data supporting HCQ for coronavirus disease 2019 (COVID-19) are limited.MethodsThis was a retrospective cohort study of hospitalized patients with COVID-19 who received ≥1 dose of HCQ at two New York City hospitals. We measured incident Grade 3 or 4 blood count and liver test abnormalities, ventricular arrhythmias, and vomiting and diarrhea within 10 days after HCQ initiation, and the proportion of patients who completed HCQ therapy. We also describe changes in Sequential Organ Failure Assessment hypoxia scores between baseline and day 10 after HCQ initiation and in-hospital mortality.ResultsNone of the 153 hospitalized patients with COVID-19 who received HCQ developed a sustained ventricular tachyarrhythmia. Incident blood count and liver test abnormalities occurred in ConclusionsHCQ appears to be reasonably safe and tolerable in most hospitalized patients with COVID-19. However, nearly one-half of patients did not improve with this treatment, highlighting the need to evaluate HCQ and alternate therapies in randomized trials

Study on prognosis of acutely ruptured intracranial aneurysms (SPARTA): a protocol for a multicentre prospective cohort study

Abstract Background Ruptured intracranial aneurysms resulting in subarachnoid haemorrhage can be treated by open surgical or endovascular treatment. Despite multiple previous studies, uncertainties on the optimal treatment practice still exists. The resulting treatment variation may result in a variable, potentially worse, patient outcome. To better inform future treatment strategies, this study aims to identify the effectiveness of different treatment strategies in patients with ruptured intracranial aneurysms by investigating long-term functional outcome, complications and cost-effectiveness. An explorative analysis of the diagnostic and prognostic value of radiological imaging will also be performed. Methods This multi-centre observational prospective cohort study will have a follow-up of 10 years. A total of 880 adult patients with a subarachnoid haemorrhage caused by a ruptured intracranial aneurysm will be included. Calculation of sample size (N = 880) was performed to show non-inferiority of clip-reconstruction compared to endovascular treatment on 1 year outcome, assessed by using the ordinal modified Rankin Scale. The primary endpoint is the modified Rankin Scale score and mortality at 1 year after the initial subarachnoid haemorrhage. Patients will receive ‘non-experimental’ regular care during their hospital stay. For this study, health questionnaires and functional outcome will be assessed at baseline, before discharge and at follow-up visits. Discussion Despite the major healthcare and societal burden, the optimal treatment strategy for patients with subarachnoid haemorrhage caused by ruptured intracranial aneurysms is yet to be determined. Findings of this comparative effectiveness study, in which in-between centre variation in practice and patient outcome are investigated, will provide evidence on the effectiveness of treatment strategies, hopefully contributing to future high value treatment standardisation. Trial registration number NCT05851989 Date of registration May 10th, 202