Roya Saffary, MD

All Publications

• Feasibility pilot trial for the Trajectories of Recovery after Intravenous propofol versus inhaled VolatilE anesthesia (THRIVE) pragmatic randomised controlled trial. BMJ open Tellor Pennington, B. R., Colquhoun, D. A., Neuman, M. D., Politi, M. C., Janda, A. M., Spino, C., Thelen-Perry, S., Wu, Z., Kumar, S. S., Gregory, S. H., Avidan, M. S., Kheterpal, S. 2023; 13 (4): e070096

  Abstract

  Millions of patients receive general anaesthesia for surgery annually. Crucial gaps in evidence exist regarding which technique, propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA), yields superior patient experience, safety and outcomes. The aim of this pilot study is to assess the feasibility of conducting a large comparative effectiveness trial assessing patient experiences and outcomes after receiving propofol TIVA or INVA.This protocol was cocreated by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 300-patient, two-centre, randomised, feasibility pilot trial. Patients 18 years of age or older, undergoing elective non-cardiac surgery requiring general anaesthesia with a tracheal tube or laryngeal mask airway will be eligible. Patients will be randomised 1:1 to propofol TIVA or INVA, stratified by centre and procedural complexity. The feasibility endpoints include: (1) proportion of patients approached who agree to participate; (2) proportion of patients who receive their assigned randomised treatment; (3) completeness of outcomes data collection and (4) feasibility of data management procedures. Proportions and 95% CIs will be calculated to assess whether prespecified thresholds are met for the feasibility parameters. If the lower bounds of the 95% CI are above the thresholds of 10% for the proportion of patients agreeing to participate among those approached and 80% for compliance with treatment allocation for each randomised treatment group, this will suggest that our planned pragmatic 12 500-patient comparative effectiveness trial can likely be conducted successfully. Other feasibility outcomes and adverse events will be described.This study is approved by the ethics board at Washington University (IRB# 202205053), serving as the single Institutional Review Board for both participating sites. Recruitment began in September 2022. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media.NCT05346588.

  View details for DOI 10.1136/bmjopen-2022-070096

  View details for PubMedID 37068889

  View details for PubMedCentralID PMC10111921

• Performance Frontiers in Operating Room Management: A Multi-Institutional Comparative Analysis Zhang, E., Saffary, R., Sharma, S., Paiste, J., Hagood, J., Mitchell, T. LIPPINCOTT WILLIAMS & WILKINS. 2022: 355-356

  View details for Web of Science ID 000840283000136

• Waste reduction in the operating room - old habits die hard, but change is possible Taylor, J., Kalra, P., Alejandro-Harper, D., Pena, N., Saffary, R., Solomon, S., Law, B., Kadry, B., Macario, A., Lu, A. LIPPINCOTT WILLIAMS & WILKINS. 2021: 1637

  View details for Web of Science ID 000713327102029

• Analysis of COVID-19 Cases' Spatial Dependence in US Counties Reveals Health Inequalities FRONTIERS IN PUBLIC HEALTH Saffary, T., Adegboye, O. A., Gayawan, E., Elfaki, F., Kuddus, M., Saffary, R. 2020; 8: 579190

  Abstract

  On March 13, 2020, the World Health Organization (WHO) declared the 2019 coronavirus disease (COVID-19) caused by the novel coronavirus SARS-CoV2 a pandemic. Since then the virus has infected over 9.1 million individuals and resulted in over 470,000 deaths worldwide (as of June 24, 2020). Here, we discuss the spatial correlation between county population health rankings and the incidence of COVID-19 cases and COVID-19 related deaths in the United States. We analyzed the spread of the disease based on multiple variables at the county level, using publicly available data on the numbers of confirmed cases and deaths, intensive care unit beds and socio-demographic, and healthcare resources in the U.S. Our results indicate substantial geographical variations in the distribution of COVID-19 cases and deaths across the US counties. There was significant positive global spatial correlation between the percentage of Black Americans and cases of COVID-19 (Moran I = 0.174 and 0.264, p < 0.0001). A similar result was found for the global spatial correlation between the percentage of Black American and deaths due to COVID-19 at the county level in the U.S. (Moran I = 0.264, p < 0.0001). There was no significant spatial correlation between the Hispanic population and COVID-19 cases and deaths; however, a higher percentage of non-Hispanic white was significantly negatively spatially correlated with cases (Moran I = -0.203, p < 0.0001) and deaths (Moran I = -0.137, p < 0.0001) from the disease. This study showed significant but weak spatial autocorrelation between the number of intensive care unit beds and COVID-19 cases (Moran I = 0.08, p < 0.0001) and deaths (Moran I = 0.15, p < 0.0001), respectively. These findings provide more detail into the interplay between the infectious disease and healthcare-related characteristics of the population. Only by understanding these relationships will it be possible to mitigate the rate of spread and severity of the disease.

  View details for DOI 10.3389/fpubh.2020.579190

  View details for Web of Science ID 000592438800001

  View details for PubMedID 33282812

  View details for PubMedCentralID PMC7690561

• New Role for the Anesthesia Preoperative Clinic: Helping to Ensure That Surgery Is the Right Choice for Patients With Serious Illness ANESTHESIA AND ANALGESIA Goldenberg, E., Saffary, R., Schmiesing, C. 2019; 129 (1): 311–15

  View details for DOI 10.1213/ANE.0000000000004178

  View details for Web of Science ID 000474206500050

• Cricoid cartilage compression devices ANAESTHESIA Saffary, R., Feliz, E., Connor, C. W. 2015; 70 (4): 504

  View details for DOI 10.1111/anae.13056

  View details for Web of Science ID 000352129900022

  View details for PubMedID 25764410

• Performance of the Sellick maneuver significantly improves when residents and trained nurses use a visually interactive guidance device in simulation PHYSIOLOGICAL MEASUREMENT Connor, C. W., Saffary, R., Feliz, E. 2013; 34 (12): 1645–56

  Abstract

  We examined the proper performance of the Sellick maneuver, a maneuver used to reduce the risk of aspiration of stomach contents during induction of general anesthesia, using a novel device that measures and visualizes the force applied to the cricoid cartilage using thin-film force sensitive resistors in a form suitable for in vivo use. Performance was tested in three stages with twenty anaesthesiology residents and twenty trained operating room nurses. Firstly, subjects applied force to the cricoid cartilage as was customary to them. Secondly, subjects used the device to guide the application of that force. Thirdly, subjects were again asked to perform the manoeuvre without visual guidance. Each test lasted 1 min and the amount of force applied was measured throughout. Overall, the Sellick maneuver was often not applied properly, with large variance between individual subjects. Performance and inter-subject consistency improved to a very highly significant degree when subjects were able to use the device as a visual guide (p < 0.001). Subsequent significant improvements in performances during the last, unguided test demonstrated that the device initiated learning.

  View details for DOI 10.1088/0967-3334/34/12/1645

  View details for Web of Science ID 000328894200006

  View details for PubMedID 24201217

• FMRP Regulates the Transition from Radial Glial Cells to Intermediate Progenitor Cells during Neocortical Development JOURNAL OF NEUROSCIENCE Saffary, R., Xie, Z. 2011; 31 (4): 1427–39

  Abstract

  During vertebrate cortical neurogenesis, radial glial cells (RGCs) serve as neural stem cells that generate neurons directly or indirectly through intermediate progenitor cells (IPCs). The transition from RGCs to IPCs is a key step in determining overall neuronal production and may underlie evolutionary expansion of the cerebral cortex. Here we show that this transition is controlled by fragile X mental retardation protein (FMRP), an RNA-binding protein whose deficiency causes fragile X syndrome. Analysis of mouse embryos electroporated with FMRP small hairpin RNA and knock-out mouse embryos lacking FMRP reveals that specific loss of FMRP causes depletion of neocortical RGCs due to an RGC-to-IPC cell fate change. The RGC depletion is associated with altered F-actin organization and can be largely rescued by overexpressing profilin 1 (Pfn1), a core actin regulatory protein promoting F-actin formation. Our data suggest that FMRP suppresses the transition from RGCs to IPCs during neocortical development by an actin-dependent mechanism.

  View details for DOI 10.1523/JNEUROSCI.4854-10.2011

  View details for Web of Science ID 000286655600028

  View details for PubMedID 21273427

  View details for PubMedCentralID PMC6623593

• Inclusion body formation and neurodegeneration are parkin independent in a mouse model of alpha-synucleinopathy JOURNAL OF NEUROSCIENCE von Coelln, R., Thomas, B., Andrabi, S. A., Lim, K. L., Savitt, J. M., Saffary, R., Stirling, W., Bruno, K., Hess, E. J., Lee, M. K., Dawson, V. L., Dawson, T. M. 2006; 26 (14): 3685–96

  Abstract

  Mutations in the genes coding for alpha-synuclein and parkin cause autosomal-dominant and autosomal-recessive forms of Parkinson's disease (PD), respectively. Alpha-synuclein is a major component of Lewy bodies, the proteinaceous cytoplasmic inclusions that are the pathological hallmark of idiopathic PD. Lewy bodies appear to be absent in cases of familial PD associated with mutated forms of parkin. Parkin is an ubiquitin E3 ligase, and it may be involved in the processing and/or degradation of alpha-synuclein, as well as in the formation of Lewy bodies. Here we report the behavioral, biochemical, and histochemical characterization of double-mutant mice overexpressing mutant human A53T alpha-synuclein on a parkin null background. We find that the absence of parkin does not have an impact on the onset and progression of the lethal phenotype induced by overexpression of human A53T alpha-synuclein. Furthermore, all major behavioral, biochemical, and morphological characteristics of A53T alpha-synuclein-overexpressing mice are not altered in parkin null alpha-synuclein-overexpressing double-mutant mice. Our results demonstrate that mutant alpha-synuclein induces neurodegeneration independent of parkin-mediated ubiquitin E3 ligase activity in nondopaminergic systems and suggest that PD caused by alpha-synuclein and parkin mutations may occur via independent mechanisms.

  View details for DOI 10.1523/JNEUROSCI.0414-06.2006

  View details for Web of Science ID 000236552400011

  View details for PubMedID 16597723

  View details for PubMedCentralID PMC6674122

• Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death JOURNAL OF NEUROSCIENCE Ko, H. S., von Coelln, R., Sriram, Kim, S. W., Chung, K. K., Pletnikova, O., Troncoso, J., Johnson, B., Saffary, R., Goh, E. L., Song, H. J., Park, B. J., Kim, M. J., Kim, S., Dawson, V. L., Dawson, T. M. 2005; 25 (35): 7968–78

  Abstract

  Autosomal-recessive juvenile parkinsonism (AR-JP) is caused by loss-of-function mutations of the parkin gene. Parkin, a RING-type E3 ubiquitin ligase, is responsible for the ubiquitination and degradation of substrate proteins that are important in the survival of dopamine neurons in Parkinson's disease (PD). Accordingly, the abnormal accumulation of neurotoxic parkin substrates attributable to loss of parkin function may be the cause of neurodegeneration in parkin-related parkinsonism. We evaluated the known parkin substrates identified to date in parkin null mice to determine whether the absence of parkin results in accumulation of these substrates. Here we show that only the aminoacyl-tRNA synthetase cofactor p38 is upregulated in the ventral midbrain/hindbrain of both young and old parkin null mice. Consistent with upregulation in parkin knock-out mice, brains of AR-JP and idiopathic PD and diffuse Lewy body disease also exhibit increased level of p38. In addition, p38 interacts with parkin and parkin ubiquitinates and targets p38 for degradation. Furthermore, overexpression of p38 induces cell death that increases with tumor necrosis factor-alpha treatment and parkin blocks the pro-cell death effect of p38, whereas the R42P, familial-linked mutant of parkin, fails to rescue cell death. We further show that adenovirus-mediated overexpression of p38 in the substantia nigra in mice leads to loss of dopaminergic neurons. Together, our study represents a major advance in our understanding of parkin function, because it clearly identifies p38 as an important authentic pathophysiologic substrate of parkin. Moreover, these results have important implications for understanding the molecular mechanisms of neurodegeneration in PD.

  View details for DOI 10.1523/JNEUROSCI.2172-05.2005

  View details for Web of Science ID 000231565100009

  View details for PubMedID 16135753

  View details for PubMedCentralID PMC6725452

• Microbial survival of space vacuum and extreme ultraviolet irradiation: strain isolation and analysis during a rocket flight FEMS MICROBIOLOGY LETTERS Saffary, R., Nandakumar, R., Spencer, D., Robb, F. T., Davila, J. M., Swartz, M., Ofman, L., Thomas, R. J., DiRuggiero, J. 2002; 215 (1): 163–68

  Abstract

  We have recovered new isolates from hot springs, in Yellowstone National Park and the Kamchatka Peninsula, after gamma-irradiation and exposure to high vacuum (10(-6) Pa) of the water and sediment samples. The resistance to desiccation and ionizing radiation of one of the isolates, Bacillus sp. strain PS3D, was compared to that of the mesophilic bacterium, Deinococcus radiodurans, a species well known for its extraordinary resistance to desiccation and high doses of ionizing radiation. Survival of these two microorganisms was determined in real and simulated space conditions, including exposure to extreme UV radiation (10-100 nm) during a rocket flight. We found that up to 15 days of desiccation alone had little effect on the viability of either bacterium. In contrast, exposure to space vacuum ( approximately 10(-6) Pa) decreased cell survival by two and four orders of magnitude for Bacillus sp. strain PS3D and D. radiodurans, respectively. Simultaneous exposure to space vacuum and extreme UV radiation further decreased the survival of both organisms, compared to unirradiated controls. This is the first report on the isolated effect of extreme UV at 30 nm on cell survival. Extreme UV can only be transmitted through high vacuum, therefore its penetration into the cells may only be superficial, suggesting that in contrast to near UV, membrane proteins rather than DNA were damaged by the radiation.

  View details for DOI 10.1111/j.1574-6968.2002.tb11386.x

  View details for Web of Science ID 000178785600025

  View details for PubMedID 12393217