Outcomes after cardiac arrest in an adult burn center

Objective

Adult burn patients who experience in-hospital cardiac arrest (CA) and undergo cardiopulmonary resuscitation (CPR) represent a unique patient population. We believe that they tend to be younger and have the added burden of the burn injury compared to other populations. Our objective was to determine the incidence, causes and outcomes following cardiac arrest (CA) and cardio-pulmonary resuscitation (CPR) within this population.

Methods

We conducted a retrospective review at the US Army Institute of Surgical Research (ISR) burn intensive care unit (BICU). Charts from 1st January 2000 through 31st August 2009 were reviewed for study. Data were collected all on adult burn patients who experienced in-hospital CA and CPR either in the BICU or associated burn operating room. Patients undergoing CPR elsewhere in our burn unit were excluded because we could not validate the time of CA since they are not routinely monitored with real-time rhythm strips. The study population included civilian burn patients from the local catchment area and burn casualties from the conflicts in Iraq and Afghanistan, but patients with do-not-resuscitate (DNR) orders were excluded.

Results

We found 57 burn patients who had in-hospital CA and CPR yielding an incidence of one or more in-hospital CA of 34 per 1000 admissions (0.34%). Fourteen of these patients (25%) survived to discharge while 43 (75%) died. The most common initial cardiac rhythm was pulseless electrical activity (50.9%). The most common etiology of CA among burn patients was respiratory failure (49.1%). The most significant variable affecting survival to discharge was duration of CPR (P < 0.01) with no patient surviving more than 7 min of CPR.

Conclusions

CPR in burn patients is sometimes effective, and those patients who survive are likely to have good neurological outcomes. However, prolonged CPR times are unlikely to result in return of spontaneous circulation and may be considered futile. Further, those who experience multiple CA are unlikely to survive to discharge.     

Involvement of antibody-dependent cell-mediated cytotoxicity in inflammatory demyelination in a mouse model of neuromyelitis optica

The progressive accumulation of extracellular amyloid plaques in the brain is a common hallmark of Alzheimer’s disease (AD). We recently identified a novel species of Aβ phosphorylated at serine residue 8 with increased propensity to form toxic aggregates as compared to non-phosphorylated species. The age-dependent analysis of Aβ depositions using novel monoclonal phosphorylation-state specific antibodies revealed that phosphorylated Aβ variants accumulate first inside of neurons in a mouse model of AD already at 2 month of age. At higher ages, phosphorylated Aβ is also abundantly detected in extracellular plaques. Besides a large overlap in the spatiotemporal deposition of phosphorylated and non-phosphorylated Aβ species, fractionized extraction of Aβ from brains revealed an increased accumulation of phosphorylated Aβ in oligomeric assemblies as compared to non-phosphorylated Aβ in vivo. Thus, phosphorylated Aβ could represent an important species in the formation and stabilization of neurotoxic aggregates, and might be targeted for AD therapy and diagnosis.     

The challenges of symptom management for patients with multimorbidity in research and practice: A thematic review

Introduction: Multimorbidity, the presence of multiple coexisting diseases or conditions, afflicts the majority of older adults, and is associated with increased mortality and healthcare utilization. In addition, multimorbidity negatively impacts quality of life and increases symptom burden. Yet, there is a dearth of evidence on how to best manage symptoms in patients with multimorbidity.

Methods: We conducted a thematic review of approaches to symptom management in multimorbidity.

Results: Research in this area has been hampered by inconsistent definitions of multimorbidity and challenges in outcome measurement. Investigations of symptom management strategies in specific disease states, like cancer, typically exclude medically complex patients. In the absence of evidence, the American Geriatrics Society's recommendations for the care of adults with multimorbidity provide a useful starting point for clinicians. We present a case to demonstrate how the AGS recommendations can be tailored to the situation of symptom management in patients with multimorbidity. We also present suggestions for future research directions.

Discussion: Multimorbidity is an incredibly common and overlooked problem in our healthcare system, and only stands to increase in relevance as patients live longer and have the opportunity to accrue a greater burden of chronic illness. A comprehensive approach to patients with multimorbidity includes focusing on patient preferences, carefully interpreting the available evidence (including both the benefits and potential harms), and thinking critically about the burden of any treatment. Taking time to elicit patient goals and preferences, and apprise patients of their prognosis if they want to know, are especially important in symptom management discussions with patients with multimorbidity.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Transaxial tomography with thallium-201 for detecting remote myocardial infarction: Comparison with planar imaging

Transaxial tomograhic imaging with thallium-201 was compared with standard, planar imaging in 38 patients with remote myocardial infarction and in 15 normal patients. Tomographic images were reconstructed from 64 views collected by a gamma camera that rotated about the anterior circumference of the patient's chest. A series of consecutive transverse-section images which encompassed the cardiac volume were reconstructed at a 6 mm plane spacing by filtered back-projection. No correction was made for attenuation losses. The set of transverse-section images was reformatted by 3-dimensional interpolation to obtain tomograms along the long and short axes of the myocardium. Tomographic and planar images were interpreted qualitatively.

Overall, tomography detected 33 of 38 (87%) prior infarctions whereas planar imaging detected 24 of 38 (63 %) (p = 0.01). Improvement of the tomographic imaging method occurred only in the combined subset of transmural inferior and subendocardial infarctions, and not in transmural anterior infarctions. Peak increases in creatinine phosphokinase were smaller in patients detected only by tomography compared with those detected by both the planar and the tomographic approach (3.1 × normal versus 10.4 × normal, p = 0.04). Five patients (13%) with prior infarction were not detected by either approach. For 6 of the 9 patients detected by tomography alone, realignment of the image data along the short and long axes of the heart was essential for making the diagnosis. Fourteen of 15 patients without infarction were normal on both planar and tomographic imaging. A single normal patient had a defect detected by both techniques, yielding a specificity of 93% for each.

We conclude that transaxial tomography significantly improves the detection of thallium-201 myocardial perfusion defects in patients with prior myocardial infarction.     

Intracerebroventricular infusion of interleukin 1 rapidly decreases peripheral cellular immune responses.

Low doses (50-200 pg or 3.1-12.4 fmol) of interleukin 1 (IL-1) infused into the brain of rats produced rapid suppression of various cellular immune responses in peripheral lymphocytes of rats. Fifteen minutes after infusion of purified IL-1 beta into the lateral ventricle, natural killer cell activity, response to phytohemagglutinin stimulation, and interleukin 2 production were markedly suppressed in lymphocytes isolated from blood and spleen. These effects were due to infusion of IL-1 into brain since they did not occur when IL-1 was infused into the cisterna magna (essentially posterior to brain) or was injected intraperitoneally. Effects of IL-1 in brain could be blocked by simultaneous infusion of alpha-melanocyte-stimulating hormone, which is known to block the biological actions of IL-1. To stimulate release of endogenous IL-1 in brain, lipopolysaccharide was infused; this produced similar effects as IL-1, and these effects also were blocked by alpha-melanocyte-stimulating hormone. At longer intervals after infusion of IL-1 and lipopolysaccharide (3, 6, and 24 hr), immune responses returned to baseline or remained suppressed; i.e., "rebound" immunopotentiation did not occur. Finally, IL-1 infusion suppressed cellular immune responses in adrenalectomized animals, thereby showing that the effects of central IL-1 on peripheral cellular immune responses were, at least in part, independent of the stimulatory effect of IL-1 on secretion of adrenal hormones. These results indicate a link from brain to peripheral immune responses by means of action of a cytokine acting in the brain.     

Detection of anti-HTLV-I Tax antibodies in HTLV-I enzyme-linked immunosorbent assay-negative individuals

The HTLV-I tax gene protein (Tax) is not packaged within the mature viral particle from which the proteins for the commercially available enzyme-linked immunosorbent assay (ELISA) are derived. Screening of 162 individuals within a cohort of white intravenous (IV) drug abusers, previously identified as having an increased incidence of HTLV-I infection, demonstrated that seven of them had antibodies to the HTLV-I Tax protein but tested negative in HTLV-I ELISAs and Western blots prepared from purified virion proteins. Three out of 35 individuals in other behaviorally defined high-risk groups also displayed this limited pattern of reactivity to HTLV-I proteins. The presence of the anti-HTLV- I p40/Tax antibodies was determined by radioimmunoprecipitation assay (RIPA), which also revealed low levels of anti-env reactivity. The specificity of the anti-p40 reactivity was confirmed on specific Tax ELISAs and Western blots prepared from recombinantly produced Tax. In vitro gene amplification by the polymerase chain reaction (PCR) was used to establish the presence of sequences homologous to HTLV-I proviral DNA in four/four of these HTLV-I ELISA negative, Tax ELISA/Tax western blot/RIPA positive individuals. These data suggest that the true incidence of HTLV-I infection within high-risk cohorts is greater than previously reported.