Early Management of Patients With Acute Heart Failure: State of the Art and Future Directions—A Consensus Document from the SAEM/HFSA Acute Heart Failure Working Group

Heart failure (HF) afflicts nearly 6 million Americans, resulting in 1 million emergency department (ED) visits and over 1 million annual hospital discharges. The majority of inpatient admissions originate in the ED; thus, it is crucial that emergency physicians and other providers involved in early management understand the latest developments in diagnostic testing, therapeutics, and alternatives to hospitalization. This article discusses contemporary ED management as well as the necessary next steps for ED‐based acute HF research.     

Cysteine pairs in the third intracellular loop of the muscarinic m1 acetylcholine receptor play a role in agonist-induced internalization

The current study investigated whether ethanol alters ATP activation of purinergic type 2 receptors (P2Rs) in the ventral tegmental area (VTA). The VTA is a key region of the brain that has been implicated in the development of alcohol addiction. We investigated the effects of ATP and ethanol on spontaneous inhibitory postsynaptic currents (sIPSCs) and the spontaneous firings in the VTA dopaminergic neurons, obtained using an enzyme-free procedure. These neurons preserved some functional GABA-releasing terminals after isolation. We found that ATP (1-200 microM) either increased or decreased the frequency of sIPSCs and the activity of VTA dopaminergic neurons. The effects of ATP on sIPSC frequency inversely correlated with its effects on dopaminergic neuron activity. The ATP-induced changes in sIPSC frequency were blocked by tetrodotoxin (a sodium channel blocker) and by suramin (a nonselective P2R antagonist). Furthermore, alpha,beta-methylene ATP, a selective P2X(1) and P2X(3) receptor agonist, increased sIPSC frequency, whereas adenosine 5'-[beta-thio]diphosphate, a preferential agonist of P2Y receptors, decreased sIPSC frequency. In experiments testing the effects of ethanol (10 and 40 mM) on sIPSCs, we found that ethanol significantly attenuated ATP-induced increase and enhanced ATP-induced decrease in sIPSC frequency. Taken together, the results demonstrate that multiple subtypes of P2Rs exist on GABA-releasing terminals that make synapses on VTA dopaminergic neurons. It seems that ATP increases sIPSC frequency involving P2X(1) and/or P2X(3) receptors, and ATP decreases sIPSC frequency involving P2YRs. These findings are also consistent with the notion that P2Rs at GABA-releasing terminals on VTA dopaminergic neurons are important targets for ethanol action.     

What's Next for Acute Heart Failure Research?

Each year over one million patients with acute heart failure (AHF) present to a United States emergency department (ED). The vast majority are hospitalized for further management. The length of stay and high postdischarge event rate in this cohort have changed little over the past decade. Therapeutic trials have failed to yield substantive improvement in postdischarge outcomes; subsequently, AHF care has changed little in the past 40 years. Prior research studies have been fragmented as either “inpatient” or “ED‐based.” Recognizing the challenges in identification and enrollment of ED patients with AHF, and the lack of robust evidence to guide management, an AHF clinical trials network was developed. This network has demonstrated, through organized collaboration between cardiology and emergency medicine, that many of the hurdles in AHF research can be overcome. The development of a network that supports the collaboration of acute care and HF researchers, combined with the availability of federally funded infrastructure, will facilitate more efficient conduct of both explanatory and pragmatic trials in AHF. Yet many important questions remain, and in this document our group of emergency medicine and cardiology investigators have identified four high‐priority research areas.     

Leveraging the Medical Context to Increase Upper Extremity Reconstruction Among Patients With Tetraplegia: A Qualitative Analysis

Objectives

To (1) characterize patients' medical experiences from initial injury until they become candidates for upper extremity reconstruction (UER); and (2) identify points in this medical context that may be most amenable to interventions designed to increase UER utilization.

Global challenges in human immunodeficiency virus and syphilis coinfection among men who have sex with men

Introduction: Syphilis and human immunodeficiency virus (HIV) coinfection disproportionately affects men who have sex with men (MSM), and the rate of coinfection has been increasing over the last decade. HIV and syphilis coinfection is particularly challenging because the infections interact synergistically thereby increasing the risk of acquisition and transmission as well as accelerating disease progression.

Areas covered: This paper reviews and summarizes the epidemiology, pathogenesis, diagnosis, clinical management and prevention of HIV and syphilis coinfection among MSM.

Expert commentary: Research does not support a different syphilis treatment for coinfected individuals; however, coinfection may warrant a recommendation for antiretroviral therapy. In order to reverse the epidemic of syphilis and HIV coinfection, there needs to be greater awareness, improved cultural sensitivity among health care providers, improved access to preventative services and increased screening for syphilis and HIV.     

Hydrodynamic gene delivery to the pig liver via an isolated segment of the inferior vena cava

Hydrodynamic gene delivery is an attractive option for non-viral liver gene therapy, but requires evaluation of efficacy, safety and clinically applicable techniques in large animal models. We have evaluated retrograde delivery of DNA to the whole liver via the isolated segment of inferior vena cava (IVC) draining the hepatic veins. Pigs (18-20 kg weight) were given the pGL3 plasmid via two programmable syringe pumps in parallel. Volumes corresponding to 2% of body weight (360-400 ml) were delivered at 100 ml s(-1) via a Y connector. The IVC segment pressure, portal venous pressure, arterial pressure, electrocardiogram (ECG) and pulse were monitored. Concurrent studies were performed in rats for interspecies comparisons. The hydrodynamic procedure generated intrahepatic vascular pressures of 101-126 mm Hg, which is approximately 4 times higher than in rodents, but levels of gene delivery were approximately 200-fold lower. Suprahepatic IVC clamping caused a fall in arterial pressure, with the development of ECG signs of myocardial ischaemia, but these abnormalities resolved rapidly. The IVC segment approach is a clinically acceptable approach to liver gene therapy. However, it is less effective in pigs than in rodents, possibly because of larger liver size or a less compliant connective tissue framework.     

The Effect of Stretching on Muscle Responses and Postural Sway Responses During Computerized Dynamic Posturography in Women and Men

Lewis NL, Brismée JM, James CR, Sizer PS, Sawyer SF. The effect of stretching on muscle responses and postural sway responses during computerized dynamic posturography in women and men.

Objective

To evaluate the effect of stretching on the parameters of postural sway and on the kinematic variables associated with balance control in women and men.

Design

Mixed repeated measures design with 2 levels.

Setting

Research laboratory.

Participants

Fifteen women and fifteen men (mean age 23.4±2.2).

Intervention

Two separate sessions of (1) lower extremity stretching and (2) no-stretching, immediately prior to balance testing with simultaneous surface electromyographic (EMG) recordings of muscle responses.

Main Outcome Measures

EMG latencies and average amplitudes for 4 lower extremity muscles for the preferred stance limb during computerized dynamic posturography (CDP) tests, specifically the Postural Evoked Response Test, Adaptation Test, Motor Control Test, Sensory Organization Test, and Unilateral Stance Test.

Results

Analyses of variance indicated no significant main effect for stretching and 2 significant main effects for gender for the Motor Control Test (P=.021) and latency of tibialis anterior (P=.009). Analyses of covariance with covariants of height and active knee extension revealed no significant main effect of stretching or of gender on muscles responses or CDP performance.

Conclusions

In both women and men, lower extremity stretching did not significantly affect muscle responses or performance during CDP.     

Severe Bordetella holmesii infection in a previously healthy adolescent confirmed by gene sequence analysis.

We describe an immunocompetent adolescent who presented with exceptionally severe Bordetella holmesii infection, including previously undescribed manifestations. Sequelae included a severe restrictive lung defect due to pulmonary fibrosis.