Life after sepsis: an international survey of survivors to understand the post-sepsis syndrome.

OBJECTIVE: In this study, we aim to describe the post-sepsis syndrome from the perspective of the sepsis survivors. DESIGN AND SETTING: The study is a prospective, observational online international survey. PARTICIPANTS: Sepsis survivors enrolled via social media from 13 September 2014 to 13 September 2016. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Physiologic, physical and psychological function post-sepsis; and patient satisfaction with sepsis-centered care. RESULTS: 1731 completed surveys from 41 countries were analyzed, with 79.9% female respondents, age 47.6 ± 14.4 years. The majority of respondents (47.8%) had sepsis within the last year. Survivors reported an increase in sensory, integumentary, digestive, breathing, chest pain, kidney and musculoskeletal problems after sepsis (all P-value <0.0001). Physical functions such as daily chores, running errands, spelling, reading and reduced libido posed increased difficulty (all P-value <0.0001). Within 7 days prior to completing the survey, the survivors reported varying degrees of anxiety, depression, fatigue and sleep disturbance. Sepsis survivors reported dissatisfaction with a number of hospital support services, with up to 29.3% of respondents stating no social services support was provided for their condition. CONCLUSIONS: Sepsis survivors suffer from a myriad of physiologic, physical and psychological challenges. Survivors overall reveal dissatisfaction with sepsis-related care, suggesting areas for improvement both in-hospital and post-discharge.

Neuropeptide PACAP in mouse liver ischemia and reperfusion injury: immunomodulation by the cAMP-PKA pathway.

UNLABELLED: Hepatic ischemia and reperfusion injury (IRI), an exogenous antigen-independent local inflammation response, occurs in multiple clinical settings, including liver transplantation, hepatic resection, trauma, and shock. The immune system and the nervous system maintain extensive communication and mount a variety of integrated responses to danger signals through intricate chemical messengers. This study examined the function and potential therapeutic potential of neuropeptide pituitary adenylate cyclase-activating polypeptides (PACAP) in a murine model of partial liver "warm" ischemia (90 minutes) followed by reperfusion. Liver IRI readily triggered the expression of intrinsic PACAP and its receptors, whereas the hepatocellular damage was exacerbated in PACAP-deficient mice. Conversely, PACAP27, or PACAP38 peptide monotherapy, which elevates intracellular cyclic adenosine monophosphate/protein kinase A (cAMP-PKA) signaling, protected livers from IRI, as evidenced by diminished serum alanine aminotransferase levels and well-preserved tissue architecture. The liver protection rendered by PACAP peptides was accompanied by diminished neutrophil/macrophage infiltration and activation, reduced hepatocyte necrosis/apoptosis, and selectively augmented hepatic interleukin (IL)-10 expression. Strikingly, PKA inhibition readily restored liver damage in otherwise IR-resistant, PACAP-conditioned mice. In vitro, PACAP treatment not only diminished macrophage tumor necrosis factor alpha/IL-6/IL-12 levels in a PKA-dependent manner, but also prevented necrosis and apoptosis in primary mouse hepatocyte cultures. CONCLUSION: Our novel findings document the importance of PACAP-mediated cAMP-PKA signaling in hepatic homeostasis and cytoprotection in vivo. Because the enhancement of neural modulation differentially regulates local inflammation and prevents hepatocyte death, these results provide the rationale for novel approaches to manage liver inflammation and IRI in transplant patients.

Activation of cyclic adenosine monophosphate-dependent protein kinase a signaling prevents liver ischemia/reperfusion injury in mice.

Hepatic ischemia/reperfusion injury (IRI) occurs in multiple clinical settings, including liver transplantation. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway inhibits hepatocellular apoptosis and regulates toll-like receptor 4-triggered inflammation responses in vitro. Here we examined the function and therapeutic potential of cAMP-PKA activation in a murine (C57/BL6) model of liver warm ischemia (90 minutes) followed by reperfusion. Liver IRI triggered cAMP-PKA activation, whereas the administration of its specific inhibitor, H89, exacerbated hepatocellular damage. Conversely, forskolin therapy, which activates PKA by elevating cAMP levels, protected livers from IRI; this was evidenced by diminished serum alanine aminotransferase levels and well-preserved tissue architecture. Liver protection due to cAMP-PKA stimulation was accompanied by diminished neutrophil and macrophage infiltration/activation, reduced hepatocyte necrosis/apoptosis, and increased cAMP response element-binding protein (CREB) expression and augmented interleukin-10 (IL-10) expression. The neutralization of IL-10 restored liver damage in otherwise ischemia/reperfusion-resistant, forskolin-treated mice. In vitro, cAMP-PKA activation diminished macrophage tumor necrosis factor α, IL-6, and IL-12 in an IL-10-dependent manner and prevented necrosis/apoptosis in primary mouse hepatocyte cultures. Our novel findings in a mouse model of liver IRI document the importance of cAMP-PKA signaling in hepatic homeostasis and cytoprotection in vivo. The activation of cAMP-PKA signaling differentially regulates local inflammation and prevents hepatocyte death, and this provides a rationale for novel therapeutic approaches to combating liver IRI in transplant recipients.

The use of augmented reality glasses in central line simulation: "see one, simulate many, do one competently, and teach everyone".

OBJECTIVE: The aim of this study was to investigate the feasibility of using augmented reality (AR) glasses in central line simulation by novice operators and compare its efficacy to standard central line simulation/teaching. DESIGN: This was a prospective randomized controlled study enrolling 32 novice operators. Subjects were randomized on a 1:1 basis to either simulation using the augmented virtual reality glasses or simulation using conventional instruction. SETTING: The study was conducted in tertiary-care urban teaching hospital. SUBJECTS: A total of 32 adult novice central line operators with no visual or auditory impairments were enrolled. Medical doctors, respiratory therapists, and sleep technicians were recruited from the medical field. MEASUREMENTS AND MAIN RESULTS: The mean time for AR placement in the AR group was 71±43 s, and the time to internal jugular (IJ) cannulation was 316±112 s. There was no significant difference in median (minimum, maximum) time (seconds) to IJ cannulation for those who were in the AR group and those who were not (339 [130, 550] vs 287 [35, 475], p=0.09), respectively. There was also no significant difference between the two groups in median total procedure time (524 [329, 792] vs 469 [198, 781], p=0.29), respectively. There was a significant difference in the adherence level between the two groups favoring the AR group (p=0.003). CONCLUSION: AR simulation of central venous catheters in manikins is feasible and efficacious in novice operators as an educational tool. Future studies are recommended in this area as it is a promising area of medical education.

Development of an advanced nomogram for myopic astigmatic wavefront-guided laser in situ keratomileusis (LASIK).

BACKGROUND AND OBJECTIVE: To identify the relationship between preoperative parameters and postoperative overcorrection or undercorrection in eyes with myopic astigmatism treated with wavefront-guided laser in situ keratomileusis (LASIK), and to develop an advanced surgical nomogram. PATIENTS AND METHODS: A retrospective chart review of 468 eyes that underwent wavefront-guided LASIK for myopia with astigmatism with the Alcon LADARVision 4000 (Alcon Laboratories, Fort Worth, TX), of which 235 had flaps created by microkeratome (OneUse; Moria Surgical, Doylestown, PA) and 233 by femtosecond laser (Intralase; AMO, Santa Ana, CA). Manifest sphere, cylinder, and spherical equivalent were recorded preoperatively and 3 months postoperatively. Various parameters from patient records were analyzed to identify which had greatest influence on outcomes. RESULTS: Manifest spherical equivalent was the most important predictor of surgical overcorrection, with the second being spherical aberration. In both groups, there was a statistically significant (P < .0001) correlation of spherical aberration with the amount of overcorrection. Using these two parameters, compensatory nomograms were derived. CONCLUSION: Surgical overcorrection in wavefront-guided LASIK for myopic astigmatism correlates positively with the amount of spherical equivalent treated and preoperative spherical aberration. Nomograms incorporating spherical aberration may improve accuracy of outcomes.