Video versus Direct Laryngoscopy for Tracheal Intubation of Critically Ill Adults.

BACKGROUND: Whether video laryngoscopy as compared with direct laryngoscopy increases the likelihood of successful tracheal intubation on the first attempt among critically ill adults is uncertain. METHODS: In a multicenter, randomized trial conducted at 17 emergency departments and intensive care units (ICUs), we randomly assigned critically ill adults undergoing tracheal intubation to the video-laryngoscope group or the direct-laryngoscope group. The primary outcome was successful intubation on the first attempt. The secondary outcome was the occurrence of severe complications during intubation; severe complications were defined as severe hypoxemia, severe hypotension, new or increased vasopressor use, cardiac arrest, or death. RESULTS: The trial was stopped for efficacy at the time of the single preplanned interim analysis. Among 1417 patients who were included in the final analysis (91.5% of whom underwent intubation that was performed by an emergency medicine resident or a critical care fellow), successful intubation on the first attempt occurred in 600 of the 705 patients (85.1%) in the video-laryngoscope group and in 504 of the 712 patients (70.8%) in the direct-laryngoscope group (absolute risk difference, 14.3 percentage points; 95% confidence interval [CI], 9.9 to 18.7; P<0.001). A total of 151 patients (21.4%) in the video-laryngoscope group and 149 patients (20.9%) in the direct-laryngoscope group had a severe complication during intubation (absolute risk difference, 0.5 percentage points; 95% CI, -3.9 to 4.9). Safety outcomes, including esophageal intubation, injury to the teeth, and aspiration, were similar in the two groups. CONCLUSIONS: Among critically ill adults undergoing tracheal intubation in an emergency department or ICU, the use of a video laryngoscope resulted in a higher incidence of successful intubation on the first attempt than the use of a direct laryngoscope. (Funded by the U.S. Department of Defense; DEVICE ClinicalTrials.gov number, NCT05239195.).

DirEct versus VIdeo LaryngosCopE (DEVICE): protocol and statistical analysis plan for a randomised clinical trial in critically ill adults undergoing emergency tracheal intubation.

INTRODUCTION: Among critically ill patients undergoing orotracheal intubation in the emergency department (ED) or intensive care unit (ICU), failure to visualise the vocal cords and intubate the trachea on the first attempt is associated with an increased risk of complications. Two types of laryngoscopes are commonly available: direct laryngoscopes and video laryngoscopes. For critically ill adults undergoing emergency tracheal intubation, it remains uncertain whether the use of a video laryngoscope increases the incidence of successful intubation on the first attempt compared with the use of a direct laryngoscope. METHODS AND ANALYSIS: The DirEct versus VIdeo LaryngosCopE (DEVICE) trial is a prospective, multicentre, non-blinded, randomised trial being conducted in 7 EDs and 10 ICUs in the USA. The trial plans to enrol up to 2000 critically ill adults undergoing orotracheal intubation with a laryngoscope. Eligible patients are randomised 1:1 to the use of a video laryngoscope or a direct laryngoscope for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is the incidence of severe complications between induction and 2 min after intubation, defined as the occurrence of one or more of the following: severe hypoxaemia (lowest oxygen saturation <80%); severe hypotension (systolic blood pressure <65 mm Hg or new or increased vasopressor administration); cardiac arrest or death. Enrolment began on 19 March 2022 and is expected to be completed in 2023. ETHICS AND DISSEMINATION: The trial protocol was approved with waiver of informed consent by the single institutional review board at Vanderbilt University Medical Center and the Human Research Protection Office of the Department of Defense. The results will be presented at scientific conferences and submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05239195).

Raising the pressure: Hemodynamic effects of splanchnic nerve stimulation.

A number of cardiovascular and neurological diseases are characterized by a dysregulation of intravascular volume distribution. The veins and arteries of the visceral organs form the so-called splanchnic vascular compartment and are the largest reservoir for intravascular blood. The blood localized in the splanchnic compartment can be mobilized in and out of the compartment via passive compression or active neurohormonal recruitment. We studied the hemodynamic effects of splanchnic nerve stimulation during five cases of irreversible electroporation (IRE) in patients with pancreatic cancer. In IRE, repeated bursts of high-voltage electrical fields are applied to visceral beds for >1 min, which induces rapid increase in blood pressure, heart rate, and cardiac output. We present the first analysis into the hemodynamic changes with splanchnic nerve stimulation and explore potential mechanisms of the hyperdynamic state. Our analysis presents the first human report of splanchnic nerve stimulation to induce hypertension and volume redistribution, introducing the splanchnic nerves as a key component of cardiovascular regulation.NEW & NOTEWORTHY Our case series provides the first detailed description of human hemodynamic effects with splanchnic nerve stimulation. Splanchnic nerve stimulation results in profound hemodynamic alteration with rapid onset of hypertension and blood mobilization.

MYC activity mitigates response to rapamycin in prostate cancer through 4EBP1-mediated inhibition of autophagy.

Cancer cells have evolved exquisitely to ignore both intrinsic and extrinsic cell death signals, and resistance to cell death is a critical challenge facing clinical oncology. Autophagy, the catabolic recycling process that involves the fusion of autophagosomes containing sequestered cargo with lysosomes, has an enigmatic role in tumorigenesis. In times of metabolic stress due to deprived nutrition or hypoxia, tumor cells use autophagy as a scavenging mechanism for maintenance of critical processes and survival. However, modulation of the extent of autophagy plays a critical role, as excessive autophagy can result in a nonapoptotic and non-necrotic cell death (sometimes referred to as Type II programmed cell death). It is likely that the genetic context of specific cancers will have an impact upon whether autophagy is primarily a mechanism for survival or cell death.

Treatment of cerebellar granule cell neurons with the neurotrophic factor pigment epithelium-derived factor in vitro enhances expression of other neurotrophic factors as well as cytokines and chemokines.

Microarray analyses demonstrated that a variety of genes was affected by treatment of cerebellar granule cell neurons with the neurotrophic factor pigment epithelium-derived factor (PEDF). The genes for neurotrophins, glial cell-derived neurotrophic factor (GDNF), and their receptors were regulated differentially in immature versus mature neurons; however, nerve growth factor (NGF), neurotrophin (NT)-3, and GDNF did not contribute to the protective effect of PEDF. Brain-derived neurotrophic factor (BDNF) seemed capable of inducing apoptosis, because a blocking antibody enhanced the protective effect of PEDF. In addition, PEDF exposure also stimulated expression of several cytokine and chemokine genes. Removal of the less than 1% of microglia in the cultures by treatment with L-leucine methyl ester, combined with enzyme-linked immunosorbent assays (ELISAs), demonstrated that the cerebellar granule cells constitutively produce three chemokines, macrophage inflammatory protein (MIP)-1alpha, MIP-2, and MIP-3alpha, whose production is enhanced further by treatment with PEDF. Blocking antibodies to each of the chemokines was protective under control conditions, suggesting that they may contribute to the "natural" apoptosis occurring in the cultures, and enhanced the effects of PEDF. Although PEDF enhanced production of all three chemokines, the blocking antibodies did not increase its protective effect against induced apoptosis. These results suggest that although PEDF enhances expression of other neurotrophic factors or chemokines, it does not exert its neuroprotective effect on cerebellar granule cells through their production.

Effect of strain and sex on mu opioid receptor-mediated G-protein activation in rat brain.

Strain and sex differences in mu opioid-mediated antinociception have been reported in rodents. The present studies evaluated mu opioid receptor-mediated G-protein activation in Lewis and Fischer 344 (F344) male and female rats using agonist-stimulated [35S]GTPgammaS binding. Compared to Lewis rats, F344 rats exhibited a 35% higher level of net DAMGO-stimulated [35S]GTPgammaS binding in striatum. Basal [35S]GTPgammaS binding was approximately 30% lower in thalamus of Lewis than F344 rats. Female Lewis rats also exhibited slightly ( approximately 15%) lower basal [35S]GTPgammaS binding in cingulate cortex relative to F344 rats of either sex. The relative efficacies of the mu partial agonists, morphine and buprenorphine, were also examined. Buprenorphine exhibited approximately 40% lower relative efficacy in the periaqueductal gray in Lewis compared to F344 rats, but no other relative efficacy differences were found between strains or sexes. Moreover, regional differences in the relative efficacy of buprenorphine were also detected in Lewis but not F344 rats. In contrast to these results, the only difference found between sexes was the 13% lower basal [35S]GTPgammaS binding in the cingulate cortex of female compared to male Lewis rats. These results suggest that differences in mu opioid receptor-mediated G-protein activation may contribute to strain differences in opioid antinociception, whereas sex differences may result predominantly from other mechanisms.

Research jobs for recent college graduates: A comparison between traditional lab technician positions and NIH's postbaccalaureate IRTA fellowship.

The features that distinguish the Postbaccalaureate IRTA experience from a normal lab tech job are the enhanced educational opportunities, greater independence, more organized social outlets and networking opportunities, life in the DC Metro area, and the NIH itself. Also, research experience looks great on a CV when applying for research jobs or graduate schools, and the NIH name and Postbaccalaureate IRTA fellowship are impressive to potential employers and admissions committees. On the other hand, lab tech jobs often require fewer commitments outside of a normal 9-to-5 work day and usually have better pay and benefits than the Postbaccalaureate IRTA fellowship. In addition, working at a specific university often carries the benefit of being closer to one's family, friends, and/or significant others. Someone who does not like cities can choose to work at a university that has ready access to the beach, mountains, or regions of the country that are more personally appealing than the Washington, DC, area. Lab tech jobs also usually require at least a two year commitment, whereas the Postbac IRTA fellowship is generally a one year commitment (possibly two). Regardless of which option you choose, you should be active in searching for a job that lets you fulfill the goals you set for yourself in the years between graduating and starting graduate or medical school. Whether those goals are to publish, get experience, save money, or just enjoy yourself, with careful questioning and circumspection, you should be able to maximize the possibility that you will meet your goals.