A systematic review of neuroprotective strategies after cardiac arrest: from bench to bedside (Part I - Protection via specific pathways).

Neurocognitive deficits are a major source of morbidity in survivors of cardiac arrest. Treatment options that could be implemented either during cardiopulmonary resuscitation or after return of spontaneous circulation to improve these neurological deficits are limited. We conducted a literature review of treatment protocols designed to evaluate neurologic outcome and survival following cardiac arrest with associated global cerebral ischemia. The search was limited to investigational therapies that were utilized to treat global cerebral ischemia associated with cardiac arrest. In this review we discuss potential mechanisms of neurologic protection following cardiac arrest including actions of several medical gases such as xenon, argon, and nitric oxide. The 3 included mechanisms are: 1. Modulation of neuronal cell death; 2. Alteration of oxygen free radicals; and 3. Improving cerebral hemodynamics. Only a few approaches have been evaluated in limited fashion in cardiac arrest patients and results show inconclusive neuroprotective effects. Future research focusing on combined neuroprotective strategies that target multiple pathways are compelling in the setting of global brain ischemia resulting from cardiac arrest

Comparison of web-based and face-to-face interviews for application to an anesthesiology training program: a pilot study.

ObjectiveThis study compared admission rates to a United States anesthesiology residency program for applicants completing face-to-face versus web-based interviews during the admissions process. We also explored factors driving applicants to select each interview type.MethodsThe 211 applicants invited to interview for admission to our anesthesiology residency program during the 2014-2015 application cycle were participants in this pilot observational study. Of these, 141 applicants selected face-to-face interviews, 53 applicants selected web-based interviews, and 17 applicants declined to interview. Data regarding applicants' reasons for selecting a particular interview type were gathered using an anonymous online survey after interview completion. Residency program admission rates and survey answers were compared between applicants completing face-to-face versus web-based interviews.ResultsOne hundred twenty-seven (75.1%) applicants completed face-to-face and 42 (24.9%) completed web-based interviews. The admission rate to our residency program was not significantly different between applicants completing face-to-face versus web-based interviews. One hundred eleven applicants completed post-interview surveys. The most common reasons for selecting web-based interviews were conflict of interview dates between programs, travel concerns, or financial limitations. Applicants selected face-to-face interviews due to a desire to interact with current residents, or geographic proximity to the residency program.ConclusionsThese results suggest that completion of web-based interviews is a viable alternative to completion of face-to-face interviews, and that choice of interview type does not affect the rate of applicant admission to the residency program. Web-based interviews may be of particular interest to applicants applying to a large number of programs, or with financial limitations

Cognitive dysfunction following desflurane versus sevoflurane general anesthesia in elderly patients: a randomized controlled trial.

UnlabelledAs life expectancy increases, more patients ≥65 years undergo general anesthesia. Anesthetic agents may contribute to postoperative cognitive dysfunction, and incidence may differ with anesthetic agents or intraoperative anesthesia depth. Responses to anesthetic adjuvants vary among elderly patients. Processed electroencephalography guidance of anesthetic may better ensure equivalent cerebral suppression. This study investigates postoperative cognitive dysfunction differences in elderly patients given desflurane or sevoflurane using processed electroencephalography guidance.IRB approved, randomized trial enrolled consenting patients ≥65 years scheduled for elective surgery requiring general anesthesia ≥120 minute duration. After written informed consent, patients were randomly assigned to sevoflurane or desflurane. No perioperative benzodiazepines were administered. Cognitive impairment was measured by an investigator blinded to group assignment using mini-Mental Status Examination (MMSE) at baseline; 1, 6, and 24 hours after the end of anesthesia. Mean arterial pressure was maintained within 20% of baseline. Anesthetic dose was adjusted to maintain moderate general anesthesia per processed electroencephalograpy (Patient State Index 25 to 50). The primary outcome measure was intergroup difference in MMSE change 1 hour after anesthesia (median; 95% confidence interval).110 patients consented; 26 were not included for analysis (no general anesthesia; withdrew consent; baseline MMSE abnormality; inability to perform postoperative MMSE; data capture failure); 47 sevoflurane and 37 desflurane were analyzed. There were no significant differences in patient characteristics; intraoperative mean blood pressure (desflurane 86.4; 81.3 to 89.6 versus sevoflurane 82.5; 80.2 to 86.1 mmHg; p = 0.42) or Patient State Index (desflurane 41.9; 39.0 to 44.0 versus sevoflurane 41.0; 37.5 to 44.0; p = 0.60) despite a lower MAC fraction in desflurane (0.82; 0.77 to 0.86) versus sevoflurane (0.96; 0.91 to 1.03; p < 0.001). MMSE decreased 1 hour after anesthesia (p < 0.001). The decrease at one hour was larger in sevoflurane (-2.5; -3.3 to -1.8) than desflurane (-1.3; -2.2 to -0.5; p = 0.03). MMSE returned to baseline by 6 hours after anesthesia.ConclusionsFor elderly patients in whom depth of anesthesia is maintained in the moderate range, both desflurane and sevoflurane are associated with transient decreases in cognitive function as measured by MMSE after anesthesia, with clinically insignificant differences between them in this setting.Trial registryClinicalTrials.gov NCT01199913

The role of Volatile Anesthetics in Cardioprotection: a systematic review.

This review evaluates the mechanism of volatile anesthetics as cardioprotective agents in both clinical and laboratory research and furthermore assesses possible cardiac side effects upon usage. Cardiac as well as non-cardiac surgery may evoke perioperative adverse events including: ischemia, diverse arrhythmias and reperfusion injury. As volatile anesthetics have cardiovascular effects that can lead to hypotension, clinicians may choose to administer alternative anesthetics to patients with coronary artery disease, particularly if the patient has severe preoperative ischemia or cardiovascular instability. Increasing preclinical evidence demonstrated that administration of inhaled anesthetics - before and during surgery - reduces the degree of ischemia and reperfusion injury to the heart. Recently, this preclinical data has been implemented clinically, and beneficial effects have been found in some studies of patients undergoing coronary artery bypass graft surgery. Administration of volatile anesthetic gases was protective for patients undergoing cardiac surgery through manipulation of the potassium ATP (KATP) channel, mitochondrial permeability transition pore (mPTP), reactive oxygen species (ROS) production, as well as through cytoprotective Akt and extracellular-signal kinases (ERK) pathways. However, as not all studies have demonstrated improved outcomes, the risks for undesirable hemodynamic effects must be weighed against the possible benefits of using volatile anesthetics as a means to provide cardiac protection in patients with coronary artery disease who are undergoing surgery

A systematic review of neuroprotective strategies after cardiac arrest: from bench to bedside (part II-comprehensive protection)

Neurocognitive deficits remain a significant source of morbidity in survivors of cardiac arrest. We conducted a literature review of treatment protocols designed to evaluate neurologic outcome and survival following global cerebral ischemia associated with cardiac arrest. The search was limited to investigational therapies that were implemented either during cardiopulmonary resuscitation or after return of spontaneous circulation in studies that included assessment of impact on neurologic outcome. Given that complex pathophysiology underlies global brain hypoxic ischemia following cardiac arrest, neuroprotective strategies targeting multiple stages of neuropathologic cascades should promise to improve survival and neurologic outcomes in cardiac arrest victims. In Part II of this review, we discuss several approaches that can provide comprehensive protection against global brain injury associated with cardiac arrest, by modulating multiple targets of neuropathologic cascades. Pharmaceutical approaches include adenosine and growth factors/hormones including brain-derived neurotrophic factor, insulin-like growth factor-1 and glycine-proline-glutamate, granulocyte colony stimulating factor and estrogen. Preclinical studies of these showed some benefit but were inconclusive in models of global brain injury involving systemic ischemia. Several medical gases that can mediate neuroprotection have been evaluated in experimental settings. These include hydrogen sulfide, hyperbaric oxygen and molecular hydrogen. Hyperbaric oxygen and molecular hydrogen showed promising results; however, further investigation is required prior to clinical application of these agents in cardiac arrest patients

Crotalus atrox venom preconditioning increases plasma fibrinogen and reduces perioperative hemorrhage in a rat model of surgical brain injury.

Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting. Separately, fibrinogen split products induce fibrinogen production, thereby elevating plasma fibrinogen levels. Thus, the hypothesis was that preconditioning with C. atrox venom will produce fibrinogen spilt products, thereby upregulating fibrinogen levels, ultimately improving perioperative hemostasis during SBI. We observed that Cv-PC SBI animals had significantly reduced intraoperative hemorrhage and postoperative hematoma volumes compared to those of vehicle preconditioned SBI animals. Cv-PC animals were also found to have higher levels of plasma fibrinogen at the time of surgery, with unchanged prothrombin time. Cv-PC studies with fractions of C. atrox venom suggest that snake venom metalloproteinases are largely responsible for the improved hemostasis by Cv-PC. Our findings indicate that Cv-PC increases plasma fibrinogen levels and may provide a promising therapy for reducing perioperative hemorrhage in elective surgeries

Hostility, Race, and Glucose Metabolism in Nondiabetic Individuals

OBJECTIVE— The present study was designed to determine whether hostility is differentially related to measures of glucose metabolism in African-Americans and Caucasians. RESEARCH DESIGN AND METHODS— The relationship of hostility, as measured by a subset of the Cook-Medley hostility scale (CMHOST) inventory items, to various parameters of glucose metabolism were examined in a young, healthy sample of male and female African-American and Caucasian volunteers. Fasting blood samples were collected during an inpatient admission, at which time the CMHOST was also administered. RESULTS— In the entire sample, the CMHOST was found to be significantly correlated with fasting glucose and insulin sensitivity, as measured by the homeostatic model assessment (HOMA). However, the relationship of hostility to these parameters of glucose metabolism was different in African-American and Caucasian subjects. Hostility was significantly related to fasting glucose in African-Americans and to insulin sensitivity and fasting insulin in Caucasian subjects. The relationship of hostility to insulin sensitivity and fasting insulin was partially dependent on BMI in Caucasians, but the relationship of hostility to fasting glucose was unrelated to BMI in African-Americans. CONCLUSIONS— Our data suggest that the relationship of hostility to measures of glucose metabolism is mediated differently in these two ethnic groups. Therefore, hostility seems to be part of a constellation of risk-related behaviors related to BMI in Caucasians but independently related to fasting glucose in African-Americans

Comparison of web-based and face-to-face interviews for application to an anesthesiology training program: a pilot study

Abstract Objectives: This study compared admission rates to a United States anesthesiology residency program for applicants completing face-to-face versus web-based interviews during the admissions process. We also explored factors driving applicants to select each interview type. Methods: The 211 applicants invited to interview for admission to our anesthesiology residency program during the 2014-2015 application cycle were participants in this pilot observational study. Of these, 141 applicants selected face-to-face interviews, 53 applicants selected web-based interviews, and 17 applicants declined to interview. Data regarding applicants' reasons for selecting a particular interview type were gathered using an anonymous online survey after interview completion. Residency program admission rates and survey answers were compared between applicants completing face-to-face versus web-based interviews. Results: One hundred twenty-seven (75.1%) applicants completed face-to-face and 42 (24.9%) completed webbased interviews. The admission rate to our residency program was not significantly different between applicants completing face-to-face versus web-based interviews. One hundred eleven applicants completed post-interview surveys. The most common reasons for selecting web-based interviews were conflict of interview dates between programs, travel concerns, or financial limitations. Applicants selected face-to-face interviews due to a desire to interact with current residents, or geographic proximity to the residency program. Conclusions: These results suggest that completion of webbased interviews is a viable alternative to completion of face-to-face interviews, and that choice of interview type does not affect the rate of applicant admission to the residency program. Web-based interviews may be of particular interest to applicants applying to a large number of programs, or with financial limitations

Dispersion as an Important Step in the Candida albicans Biofilm Developmental Cycle

Biofilms are dynamic microbial communities in which transitions between planktonic and sessile modes of growth occur interchangeably in response to different environmental cues. In the last decade, early events associated with C. albicans biofilm formation have received considerable attention. However, very little is known about C. albicans biofilm dispersion or the mechanisms and signals that trigger it. This is important because it is precisely C. albicans cells dispersed from biofilms that are the main culprits associated with candidemia and establishment of disseminated invasive disease, two of the gravest forms of candidiasis. Using a simple flow biofilm model recently developed by our group, we have performed initial investigations into the phenomenon of C. albicans biofilm dispersion, as well as the phenotypic characteristics associated with dispersed cells. Our results indicate that C. albicans biofilm dispersion is dependent on growing conditions, including carbon source and pH of the media used for biofilm development. C. albicans dispersed cells are mostly in the yeast form and display distinct phenotypic properties compared to their planktonic counterparts, including enhanced adherence, filamentation, biofilm formation and, perhaps most importantly, increased pathogenicity in a murine model of hematogenously disseminated candidiasis, thus indicating that dispersed cells are armed with a complete arsenal of “virulence factors” important for seeding and establishing new foci of infection. In addition, utilizing genetically engineered strains of C. albicans (tetO-UME6 and tetO-PES1) we demonstrate that C. albicans biofilm dispersion can be regulated by manipulating levels of expression of these key genes, further supporting the evidence for a strong link between biofilms and morphogenetic conversions at different stages of the C. albicans biofilm developmental cycle. Overall, our results offer novel and important insight into the phenomenon of C. albicans biofilm dispersion, a key part of the biofilm developmental cycle, and provide the basis for its more detailed analysis