The impact of severe acidemia on neurologic outcome of cardiac arrest survivors undergoing therapeutic hypothermia

Introduction

Therapeutic Hypothermia (TH) has become a standard of care in improving neurological outcomes in cardiac arrest (CA) survivors. Previous studies have defined severe acidemia as plasma pH < 7.20. We investigated the influence of severe acidemia at the time of initiation of TH on neurological outcome in CA survivors.

Methods

A retrospective analysis was performed on 196 consecutive CA survivors (out-of-hospital CA and in-hospital CA) who underwent TH with endovascular cooling between January 2007 and October 2012. Arterial blood gas drawn prior to initiation of TH was utilized to measure pH in all patients. Shockable and non-shockable CA patients were divided into two sub-groups based on pH (pH < 7.2 and pH ≥ 7.2). The primary end-point was measured using the Pittsburgh Cerebral Performance Category (CPC) scale prior to discharge from the hospital: good (CPC 1 and 2) and poor (CPC 3 to 5) neurologic outcome.

Results

Sixty-two percent of shockable CA patients with pH ≥ 7.20 had good neurological outcome as compared to 34% patients with pH < 7.20. Shockable CA patients with pH ≥ 7.20 were 3.3 times more likely to have better neurological outcome when compared to those with pH <7.20 [p = 0.013, OR 3.3, 95% CI (1.28–8.45)]. In comparison, non-shockable CA patients with p ≥ 7.20 did not have a significantly different neurological outcome as compared to those with pH < 7.20 [p = 0.97, OR 1.02, 95% CI (0.31–3.3)].

Conclusion

Presence of severe acidemia at initiation of TH in shockable CA survivors is significantly associated with poor neurological outcomes. This effect was not observed in the non-shockable CA survivors.     

An observational study of patient selection criteria for post-cardiac arrest therapeutic hypothermia

Background

To date, there is no comprehensive assessment of how therapeutic hypothermia and post-arrest care are being implemented clinically. At this stage in the translation of post-arrest science to clinical practice, this analysis is overdue. This study examines the first step of post-arrest care – the selection of patients for TH and post-arrest care.

Methods

We conducted a systematic review to search for all publicly available TH and post-arrest protocols. Observational data was reported and no statistical inferences were made.

Results

Notable variation was observed in the following selection criteria: total ischemic time and hemodynamic requirements. Additionally, only some of the criteria were evidence based.

Conclusion

This study demonstrates the wide range and variety of patient selection criteria that are being used for implementation of post-cardiac arrest care. The consequences of this selection criteria variability are currently unmeasured and likely underestimated. Variability is likely to breed inefficiency. Some patients who could benefit do not get treated. Other patients get cooled, yet will never regain consciousness. This variability may be important when considering inter-hospital variation in post-arrest care and outcomes.     

Preexposure of murine macrophages to CpG oligonucleotide results in a biphasic tumor necrosis factor alpha response to subsequent lipopolysaccharide challenge

Bacterial DNA and synthetic oligonucleotides containing CpG sequences (CpG-DNA and CpG-ODN) provoke a proinflammatory cytokine response (tumor necrosis factor alpha [TNF-alpha], interleukin-12 [IL-12], and IL-6) and increased mortality in lipopolysaccharide (LPS)-challenged mice via a TNF-alpha-mediated mechanism. It was hypothesized that preexposure of macrophages to CpG-ODN would result in an increased TNF-alpha response to subsequent LPS challenge in vitro. Using the murine macrophage cell line RAW 264.7, we demonstrated both a rapid proinflammatory cytokine response (TNF-alpha) and a delayed inhibitory cytokine response (IL-10) with CpG-ODN. Preexposure of macrophages to CpG-ODN for brief periods (1 to 3 h) augmented TNF-alpha secretion and mRNA accumulation following subsequent LPS challenge (1 microg/ml). However, prolonged preexposure to CpG-ODN (6 to 9 h) resulted in suppression of the TNF-alpha protein and mRNA response to LPS. The addition of anti-IL-10 antibody to CpG-ODN during preexposure resulted in an increase in the LPS-induced TNF-alpha response over that induced by CpG-ODN preexposure alone. Thus, while brief preexposure of macrophages to CpG-ODN augments the proinflammatory cytokine response to subsequent LPS challenge, prolonged preexposure elicits IL-10 production, which inhibits the TNF-alpha response. Although the initial proinflammatory effects of CpG-DNA are well established, the immune response to CpG-DNA may also include autocrine or paracrine feedback mechanisms, leading to a complex interaction of proinflammatory and inhibitory cytokines.     

Outcomes after vascular resection during curative-intent resection for hilar cholangiocarcinoma: a multi-institution study from the US extrahepatic biliary malignancy consortium

Background

Surgical resection is the cornerstone of curative-intent therapy for patients with hilar cholangiocarcinoma (HC). The role of vascular resection (VR) in the treatment of HC in western centres is not well defined.

Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking

Chronic intermittent access to alcohol leads to the escalation of alcohol intake, similar to binge drinking in humans. Converging lines of evidence suggest that impairment of medial prefrontal cortex (mPFC) cognitive function and overactivation of the central nucleus of the amygdala (CeA) are key factors that lead to excessive drinking in dependence. However, the role of the mPFC and CeA in the escalation of alcohol intake in rats with a history of binge drinking without dependence is currently unknown. To address this issue, we examined FBJ murine osteosarcoma viral oncogene homolog (Fos) expression in the mPFC, CeA, hippocampus, and nucleus accumbens and evaluated working memory and anxiety-like behavior in rats given continuous (24 h/d for 7 d/wk) or intermittent (3 d/wk) access to alcohol (20% vol/vol) using a two-bottle choice paradigm. The results showed that abstinence from alcohol in rats with a history of escalation of alcohol intake specifically recruited GABA and corticotropin-releasing factor (CRF) neurons in the mPFC and produced working memory impairments associated with excessive alcohol drinking during acute (24–72 h) but not protracted (16 –68 d) abstinence. Moreover, abstinence from alcohol was associated with a functional disconnection of the mPFC and CeA but not mPFC and nucleus accumbens. These results show that recruitment of a subset of GABA and CRF neurons in the mPFC during withdrawal and disconnection of the PFC–CeA pathway may be critical for impaired executive control over motivated behavior, suggesting that dysregulation of mPFC interneurons may be an early index of neuroadaptation in alcohol dependence.     

COVID-19 risk index (CRI): a simple and validated emergency department risk score that predicts mortality and the need for mechanical ventilation

Journal of Thrombosis and Thrombolysis - Although certain risk factors have been associated with morbidity and mortality, validated emergency department (ED) derived risk prediction models specific...     

Type 1 Diabetes Development Requires Both CD4+ and CD8+ T cells and Can Be Reversed by Non-Depleting Antibodies Targeting Both T Cell Populations

Type 1 diabetes development in NOD mice appears to require both CD4⁺ and CD8⁺ T cells. However, there are some situations where it has been suggested that either CD4⁺ or CD8⁺ T cells are able to mediate diabetes in the absence of the other population. In the case of transgenic mice, this may reflect the numbers of antigen-specific T cells able to access the pancreas and recruit other cell types such as macrophages leading to a release of high concentrations of damaging cytokines. Previous studies examining the requirement for CD8⁺ T cells have used antibodies specific for CD8α. It is known that CD8α is expressed not only on αβ T cells, but also on other cell types, including a DC population that may be critical for presenting islet antigen in the pancreatic draining lymph nodes. Therefore, we have re-examined the need for both CD4⁺ and CD8⁺ T cell populations in diabetes development in NOD mice using an antibody to CD8β. Our studies indicate that by using highly purified populations of T cells and antibodies specific for CD8⁺ T cells, there is indeed a need for both cell types. In accordance with some other reports, we found that CD4⁺ T cells appeared to be able to access the pancreas more readily than CD8⁺ T cells. Despite the ability of CD4⁺ T cells to recruit CD11b class II positive cells, diabetes did not develop in the absence of CD8⁺ T cells. These studies support the observation that CD8⁺ T cells may be final effector cells. As both T cell populations are clearly implicated in diabetes development, we have used a combination of non-depleting antibodies to target both CD4-positive and CD8-positive cells and found that this antibody combination was able to reverse diabetes onset in NOD mice as effectively as anti-CD3 antibodies.     

A moderately high fat diet promotes salt-sensitive hypertension in obese zucker rats by impairing nitric oxide production

The objective of this research was to examine the contribution of a moderately high fat (MHF) diet to the development of salt-sensitive hypertension in obese Zucker rats. Lean and obese Zucker rats were fed either a MHF diet or a diet of standard rat chow (control diet) for 10 weeks. From week 4 through week 10, the drinking water was supplemented with 1% NaCl. Blood pressure was measured weekly, and urinary excretion of nitric oxide metabolites (NO(x)) was determined at weeks 4 and 10. At week 10, renal nitric oxide synthase (NOS) activity was assessed in kidney homogenates. Blood pressures of obese, but not lean, rats on the MHF fat diet were significantly increased by salt-supplementation, whereas blood pressures of rats on the control diet were not appreciably affected. NO(x) excretion was increased in response to salt-supplementation in rats on the control diet, with the effect being particularly dramatic in obese rats. After salt-supplementation, NO(x) excretion by rats on the MHF diet was lower than rats on the control diet. In obese rats on the MHF diet, this decrease in NO production was accompanied by a reduction in renal NOS activity. These results indicate that obese rats are more inclined than lean rats to develop diet-induced hypertension in response to a moderately high fat, salt-supplemented diet. Furthermore, they suggest that MHF diet-induced defects in NO production may promote the salt-sensitivity of blood pressure in obese Zucker rats, which appear to require more NO to maintain blood pressure during a salt challenge.