Recent Submissions

  • Novel Myh11 Dual Reporter Mouse Model Provides Definitive Labeling and Identification of Smooth Muscle Cells - Brief Report

    Ruan, Jian; Zhang, Lu; Hu, Donghua; Qu, Xianghu; Yang, Fan; Chen, Fuxue; He, Xiangqin; Shen, Jian; Dong, Kunzhe; Sweet, Megan; et al. (Wolters Kluwer Health, 2020-12-24)
    Objective: Myh11 encodes a myosin heavy chain protein that is specifically expressed in smooth muscle cells (SMCs) and is important for maintaining vascular wall stability. The goal of this study is to generate a Myh11 dual reporter mouse line for definitive visualization of MYH11+SMCs in vivo. Approach and Results: We generated a Myh11 knock-in mouse model by inserting LoxP-nlacZ-4XpolyA-LoxP-H2B-GFP-polyA-FRT-Neo-FRT reporter cassette into the Myh11 gene locus. The nuclear (n) lacZ-4XpolyA cassette is flanked by 2 LoxP sites followed by H2B-GFP (histone 2B fused green fluorescent protein). Upon Cre-mediated recombination, nlacZ-stop cassette is removed thereby permitting nucleus localized H2B-GFP expression. Expression of the nuclear localized lacZ or H2B-GFP is under control of the endogenous Myh11 promoter. Nuclear lacZ was expressed specifically in SMCs at embryonic and adult stages. Following germline Cre-mediated deletion of nuclear lacZ, H2B-GFP was specifically expressed in the nuclei of SMCs. Comparison of nuclear lacZ expression with Wnt1Creand Mef2cCremediated-H2B-GFP expression revealed heterogenous origins of SMCs from neural crest and second heart field in the great arteries and coronary vessels adjacent to aortic root. Conclusions: The Myh11 knock-in dual reporter mouse model offers an exceptional genetic tool to visualize and trace the origins of SMCs in mice.
  • Patient Characteristics and Outcomes Associated with Decline in Stroke Volumes During the Early COVID-19 Pandemic

    Wallace, Adam N.; Asif, Kaiz S.; Sahlein, Daniel H.; Warach, Steven J.; Malisch, Timothy; LaFranchise, E. Francis; Geraghty, Scott; Kreitel, K. Derek; LaMonte, Marian P.; Miley, Jefferson T.; et al. (Elsevier Inc., 2020-12-26)
    Background and Purpose: Delayed evaluation of stroke may contribute to COVID-19 pandemic-related morbidity and mortality. This study evaluated patient characteristics, process measures and outcomes associated with the decline in stroke presentation during the early pandemic. Methods: Volumes of stroke presentations, intravenous thrombolytic administrations, and mechanical thrombectomies from 52 hospitals from January 1-June 30, 2020 were analyzed with piecewise linear regression and linear spline models. Univariate analysis compared pandemic (case) and pre-pandemic (control) groups defined in relation to the nadir of daily strokes during the study period. Significantly different patient characteristics were further evaluated with logistic regression, and significantly different process measures and outcomes were re-analyzed after propensity score matching. Results: Analysis of 7,389 patients found daily stroke volumes decreased 0.91/day from March 12–26 (p < 0.0001), reaching a nadir 35.0% less than expected, and increased 0.15 strokes/day from March 27-June 23, 2020 (p < 0.0001). Intravenous thrombolytic administrations decreased 3.3/week from February 19-March 31 (p = 0.0023), reaching a nadir 33.4% less than expected, and increased 1.4 administrations/week from April 1-June 23 (p < 0.0001). Mechanical thrombectomy volumes decreased by 1.5/week from February 19-March 31, 2020 (p = 0.0039), reaching a nadir 11.3% less than expected. The pandemic group was more likely to ambulate independently at baseline (p = 0.02, OR = 1.60, 95% CI = 1.08–2.42), and less likely to present with mild stroke symptoms (NIH Stroke Scale ≤ 5; p = 0.04, OR = 1.01, 95% CI = 1.00–1.02). Process measures and outcomes of each group did not differ, including door-to-needle time, door-to-puncture time, and successful mechanical thrombectomy rate. Conclusion: Stroke presentations and acute interventions decreased during the early COVID-19 pandemic, at least in part due to patients with lower baseline functional status and milder symptoms not seeking medical care. Public health messaging and initiatives should target these populations.
  • TELEmedicine for Patients With Inflammatory Bowel Disease (TELE-IBD) Does Not Improve Depressive Symptoms or General Quality of Life Compared With Standard Care at Tertiary Referral Centers

    Schliep, Matthew; Chudy-Onwugaje, Kenechukwu; Abutaleb, Ameer; Langenberg, Patricia; Regueiro, Miguel; Schwartz, David A; Tracy, J Kathleen; Ghazi, Leyla; Patil, Seema A; Quezada, Sandra; et al. (Oxford University Press, 2020-01-31)
    A total of 217 participants were included in this analysis. After 1 year, there was no significant difference in the change in MHI-5 (TELE-IBD W +3.0 vs TELE-IBD EOW +0.7 vs standard care +3.4; P = 0.70), MCS (TELE-IBD W +1.4 vs TELE-IBD EOW +1.0 vs standard care +2.5; P = 0.89), and PCS scores (TELE-IBD W +0.4 vs TELE-IBD EOW +0.6 vs standard care +3.7; P = 0.06) between the groups.
  • Proactive Drug Monitoring Is Associated With Higher Persistence to Infliximab and Adalimumab Treatment and Lower Healthcare Utilization Compared With Reactive and Clinical Monitoring

    Syed, Nauroz; Tolaymat, Mazen; Brown, Sara A; Sivasailam, Barathi; Cross, Raymond K (Oxford University Press, 2020-06-05)
    Background: Serum drug-level assays for infliximab (IFX) and adalimumab (ADA) are widely available and are most often obtained reactively, to determine the next steps in patients with loss of response. Studies done thus far on the use of these assays proactively, or during symptom remission, have had mixed results. Here we investigate persistence on therapy and healthcare utilization in patients on 3 drug-level monitoring strategies. Methods: We conducted a retrospective chart review of 235 patients treated for both Crohn disease and ulcerative colitis on either IFX or ADA. Monitoring strategy was defined as proactive if patients underwent testing at predefined time points regardless of symptoms or signs of disease, reactive if done during relapse, or control if no drug levels were obtained. Groups were compared on persistence on original therapeutic at 1 and 2 years as well as on various measures of healthcare utilization during the 2-year follow-up period. Results: Proactive drug monitoring was associated with a higher likelihood of persistence on therapy at 1 year when compared with the control (odds ratio [OR] = 4.76, 95% confidence interval [CI] = 1.65, 13.67) and reactive groups (OR = 6.10, CI = 2.19, 17.02). Similarly, at 2 years, proactive monitoring was superior to the control (OR = 5.41, CI = 2.26, 12.94) and reactive groups (OR = 4.51, CI = 1.88, 10.80). Proactive monitoring was also associated with lower healthcare utilization across almost all measures related to inflammatory bowel disease. Conclusions: Proactive drug monitoring increases persistence on IFX and ADA in patients with ulcerative colitis or Crohn disease and decreases overall healthcare utilization in these patients. Lay Summary Proactive drug monitoring of infliximab and adalimumab in Crohn disease and ulcerative colitis was associated with a higher likelihood of staying on the original therapeutic at 1 and 2 years, as well as lower healthcare utilization. © 2020 Crohn’s & Colitis Foundation.
  • Commentary: We need to know more about erythropoietin

    D'Ambra, Michael N. (Elsevier BV, 2020-07-31)
  • Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

    Patel, Y.; Carr, V.J.; HongL.E. (2020-08-26)
    Importance: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. Objective: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. Design, Setting, and Participants: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. Main Outcomes and Measures: Interregional profiles of group difference in cortical thickness between cases and controls. Results: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders. Conclusions and Relevance: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.
  • Personal protective equipment in the siege of respiratory viral pandemics: strides made and next steps

    Eke, U.A.; Eke, A.C. (Taylor and Francis Ltd., 2020-12-24)
    Introduction: In December 2019, SARS-CoV-2 originated from China, and spread rapidly to several countries, bringing a frightening scarcity of personal protective equipment (PPE). The CDC recommends N95 or higher-level particulate filtering respirators as part of the PPE while caring for patients with COVID-19, with facemasks as an alternative; and cloth face-coverings in public where social distancing of at least 6 ft. is not feasible. With new evidence about the efficacy of facemasks, knowledge gaps remain. Areas covered: This reviews the history of respiratory viral pandemics and PPE use, exploring the influenza pandemics of the 20th and 21st century, and prior coronavirus pandemics. A literature search of PubMed and google was done between March 22nd to May 2nd, and on September 28, 2020. The evidence for PPE is described, to delineate their efficacy and 'best safe' practices. Solutions to ameliorate pandemic preparedness to meet surge-capacity to efficiently combat future pandemics, should they arise, are discussed. Expert opinion: PPE, when used appropriately in addition to other infection control measures, is effective protection during respiratory viral pandemics. The current evidence suggests that wearing facemasks in the community is protective, especially if used consistently and correctly with other infection control measures such as hand hygiene. Copyright 2020 Informa UK Limited, trading as Taylor & Francis Group.
  • Optimizing pharmacokinetics-pharmacodynamics of antimicrobial management in patients with sepsis: A review

    Phe, K.; Heil, E.L.; Tam, V.H. (Oxford University Press, 2020-07-20)
    Critically ill patients with sepsis or septic shock are at an increased risk of death. Early and aggressive interventions are essential for improving clinical outcomes. There are a number of therapeutic and practical challenges in the management of antimicrobials in patients with sepsis. These include the timely selection and administration of appropriate antimicrobials, significant physiological alterations that can influence antimicrobial pharmacokinetics, and significant interpatient variability of antimicrobial concentrations using standard dosing approaches. Understanding the impact of these factors on the probability of attaining pharmacokinetic-pharmacodynamic target goals is essential to guide optimal therapy. Using rapid diagnostic technology could facilitate timely selection of antimicrobials, and therapeutic drug monitoring would provide a more individualized dosing approach. Using an interdisciplinary sepsis team would also be beneficial in coordinating efforts to overcome the challenges encountered during this critical period to ensure optimal care. Copyright The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
  • Considerations for empiric antimicrobial therapy in sepsis and septic shock in an era of antimicrobial resistance

    Strich, J.R.; Heil, E.L.; Masur, H. (Oxford University Press, 2020-07-21)
    Patients with sepsis present across a spectrum of infection sites and severity of illnesses requiring complex decision making at the bedside as to when prompt antibiotics are indicated and which regimen is warranted. Many hemodynamically stable patients with sepsis and low acuity of illness may benefit from further work up before initiating therapy, whereas patients with septic shock warrant emergent broad-spectrum antibiotics. The precise empiric regimen is determined by assessing patient and epidemiological risk factors, likely source of infection based on presenting signs and symptoms, and severity of illness. Hospitals should implement quality improvement measures to aid in the rapid and accurate diagnosis of septic patients and to ensure antibiotics are given to patients in an expedited fashion after antibiotic order. Copyright 2020 Oxford University Press. All rights reserved.
  • Model-Based Approach to Improve Clinical Outcomes in Neonates With Opioid Withdrawal Syndrome Using Real-World Data

    Wijekoon, N.; Aduroja, O.; Biggs, J.M.; El-Metwally, D.; Gopalakrishnan, M. (Wiley, 2020-10-29)
    At least 60% of the neonates with opioid withdrawal syndrome (NOWS) require morphine to control withdrawal symptoms. Currently, the morphine dosing strategies are empiric, not optimal and associated with longer hospital stay. The aim of the study was to develop a quantitative, model-based, real-world data-driven approach to morphine dosing to improve clinical outcomes, such as reducing time on treatment. Longitudinal morphine dose, clinical response (Modified Finnegan Score (MFS)), and baseline risk factors were collected using a retrospective cohort design from the electronic medical records of neonates with NOWS (N = 177) admitted to the University of Maryland Medical Center. A dynamic linear mixed effects model was developed to describe the relationship between MFS and morphine dose adjusting for baseline risk factors using a split-sample data approach (70% training: 30% test). The training model was evaluated in the test dataset using a simulation based approach. Maternal methadone and benzodiazepine use, and race were significant predictors of the MFS response. Positive autocorrelations of 0.56 and 0.12 were estimated between consecutive MFS responses. On an average, for a 1,000 ?g increase in the morphine dose, the MFS decreased by 0.3 units. The model evaluation showed that observed and predicted median time on treatment were similar (13.0 vs. 13.8 days). A model-based framework was developed to describe the MFS -morphine dose relationship using real-world data that could potentially be used to develop an adaptive, individualized morphine dosing strategy to improve clinical outcomes in infants with NOWS. Copyright 2020 The Authors. Clinical Pharmacology & Therapeutics Copyright 2020 American Society for Clinical Pharmacology and Therapeutics
  • Extracellular vesicles from red blood cells and their evolving roles in health, coagulopathy and therapy

    Thangaraju, K.; Neerukonda, S.N.; Katneni, U.; Buehler, P.W. (MDPI AG, 2020-12-25)
    Red blood cells (RBCs) release extracellular vesicles (EVs) including both endosome-de-rived exosomes and plasma-membrane-derived microvesicles (MVs). RBC-derived EVs (RBCEVs) are secreted during erythropoiesis, physiological cellular aging, disease conditions, and in response to environmental stressors. RBCEVs are enriched in various bioactive molecules that facilitate cell to cell communication and can act as markers of disease. RBCEVs contribute towards physiological adaptive responses to hypoxia as well as pathophysiological progression of diabetes and genetic non-malignant hematologic disease. Moreover, a considerable number of studies focus on the role of EVs from stored RBCs and have evaluated post transfusion consequences associated with their exposure. Interestingly, RBCEVs are important contributors toward coagulopathy in hematological disorders, thus representing a unique evolving area of study that can provide insights into molecular mechanisms that contribute toward dysregulated hemostasis associated with several disease conditions. Relevant work to this point provides a foundation on which to build further studies focused on unraveling the potential roles of RBCEVs in health and disease. In this review, we provide an analysis and summary of RBCEVs biogenesis, composition, and their biological function with a special emphasis on RBCEV pathophysiological contribution to coagulopathy. Further, we consider potential therapeutic applications of RBCEVs. Copyright 2020 by the authors. Licensee MDPI, Basel, Switzerland.
  • Insulin resistance in skeletal muscle of chronic stroke

    Ryan, A.S.; Hafer-Macko, C.; Ortmeyer, H.K. (MDPI AG, 2020-12-26)
    A stroke can lead to reduced mobility affecting skeletal muscle mass and fatty infiltration which could lead to systemic insulin resistance, but this has not been examined and the mechanisms are currently unknown. The objective was to compare the effects of in vivo insulin on skeletal muscle glycogen synthase (GS) activity in paretic (P) and nonparetic (NP) skeletal muscle in chronic stroke, and to compare to nonstroke controls. Participants were mild to moderately disabled adults with chronic stroke (n = 30, 60 ± 8 years) and sedentary controls (n = 35, 62 ± 8 years). Insulin sensitivity (M) and bilateral GS activity were determined after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Stroke subjects had lower aerobic capacity than controls, but M was not significantly different. Insulin-stimulated activities of GS (independent, total, fractional), as well as absolute differences (insulin minus basal) and the percent change (insulin minus basal, relative to basal) in GS activities, were all significantly lower in P versus NP muscle. Basal GS fractional activity was 3-fold higher, and the increase in GS fractional activity during the clamp was 2-fold higher in control versus P and NP muscle. Visceral fat and intermuscular fat were associated with lower M. The effect of in vivo insulin to increase GS fractional activity was associated with M in control and P muscle. A reduction in insulin action on GS in paretic muscle likely contributes to skeletal muscle-specific insulin resistance in chronic stroke. Copyright 2020 by the authors. Licensee MDPI, Basel, Switzerland.
  • Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection

    Saccone, G.; Cojocaru, L.; The WAPM (World Association of Perinatal Medicine) Working Group on COVID-19 (John Wiley and Sons Ltd, 2020-09-14)
    Objectives: To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. Methods: This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. Results: In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251 (27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. Conclusions: SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. Copyright 2020 International Society of Ultrasound in Obstetrics and Gynecology. Copyright 2020 International Society of Ultrasound in Obstetrics and Gynecology
  • Full-thickness Skin Micro-columns within a Dermal Matrix: A Novel Method for "donor-free" Skin Replacement

    Cooper, L.; Gronet, E.; Carlsson, A.; Chan, R. (Lippincott Williams and Wilkins, 2020-12-18)
    Summary: Split-thickness skin graft has been the standard in the coverage of large full-thickness skin defects. However, donor sites can be associated with significant pain and scarring. Further, the recipient sites frequently lack some basic skin functions, such as temperature regulation, uniform texture, appropriate color, normal pliability, elasticity, and lubrication. Full-thickness skin grafts, while able to more adequately recapitulate skin function, have even greater donor site requirements. Implantation of full-thickness skin micro-columns is a relatively novel concept in which the skin is harvested orthogonally rather than tangentially. These micro-columns contain elements of full-thickness skin grafts, including reticular dermal fibroblasts, hair follicles, skin adnexa, and adipose tissue - all elements that contribute to skin function. Notably, it has been shown that the diameter of the skin micro-columns determine donor site morbidity; however, in most cases, full-thickness skin micro-column harvest results in a trivial donor site far less invasive or morbid than a traditional full-thickness skin graft or split-thickness skin graft harvest. Here, we present 2 cases in which full-thickness skin micro-columns were harvested and implanted into a bilayer dermal regeneration matrix (Integra) to achieve durable single-stage skin replacement with practically no donor site morbidity. Copyright 2021 Lippincott Williams and Wilkins. All rights reserved.
  • Monocyte Subsets With High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8

    Das, A.; Wang, X.; Kang, J.; Coulter, A.; Shetty, A.C.; Bachu, M.; Brooks, S.R.; Dell'Orso, S.; Foster, B.L.; Fan, X.; et al. (John Wiley and Sons Inc, 2020-08-17)
    Osteoclasts (OCs) are bone-resorbing cells formed by the serial fusion of monocytes. In mice and humans, three distinct subsets of monocytes exist; however, it is unclear if all of them exhibit osteoclastogenic potential. Here we show that in wild-type (WT) mice, Ly6Chi and Ly6Cint monocytes are the primary source of OC formation when compared to Ly6C- monocytes. Their osteoclastogenic potential is dictated by increased expression of signaling receptors and activation of preestablished transcripts, as well as de novo gain in enhancer activity and promoter changes. In the absence of interferon regulatory factor 8 (IRF8), a transcription factor important for myelopoiesis and osteoclastogenesis, all three monocyte subsets are programmed to display higher osteoclastogenic potential. Enhanced NFATc1 nuclear translocation and amplified transcriptomic and epigenetic changes initiated at early developmental stages direct the increased osteoclastogenesis in Irf8-deficient mice. Collectively, our study provides novel insights into the transcription factors and active cis-regulatory elements that regulate OC differentiation. Copyright 2020 American Society for Bone and Mineral Research (ASBMR). Copyright 2020 American Society for Bone and Mineral Research (ASBMR)
  • Leveraging Heterogeneity in Systemic Lupus Erythematosus for New Therapies

    Allen, M.E.; Rus, V.; Szeto, G.L. (Elsevier Ltd, 2020-10-09)
    Systemic lupus erythematosus (SLE) is a multisystem, chronic autoimmune disease where treatment varies by patient and disease activity. Strong preclinical results and clinical correlates have motivated development of many drugs, but many of these have failed to achieve efficacy in clinical trials. FDA approval of belimumab in 2011 was the first successful SLE drug in nearly six decades. In this article, we review insights into the molecular and clinical heterogeneity of SLE from transcriptomics studies and detail their potential impact on drug development and clinical practices. We critically examine the pipeline of SLE drugs, including past failures and their associated lessons and current promising approaches. Finally, we identify opportunities for integrating these findings and drug development with new multidisciplinary advances to enhance future SLE treatment. Copyright 2020 Elsevier Ltd
  • The incidence of persistent postoperative opioid use among U.S. veterans: A national study to identify risk factors

    Namiranian, K.; Siglin, J.; Sorkin, J.D. (Elsevier Inc., 2020-09-30)
    Objective: To calculate the incidence and identify the predictors of persistent postoperative opioid use at different postoperative days. Background data: A subset of surgical patients continues to use long-term opioids. The importance of the risk factors at different postoperative days is not known. Design: A historical cohort. Setting: Postoperative period. Patients: Opioid-naive U.S. veterans. Interventions: The surgical group had any one of 19 common invasive procedures. The control group is a 10% random sample. Each control was randomly assigned a surgery date. Measurements: The outcomes were the presence of persistent opioid use as determined by continued filling of prescriptions for opioids on postoperative days 90, 180, 270, and 365. Main results: A total of 183,430 distinct surgical cases and 1,318,894 controls were identified. 1.0% of the surgical patients were using opioids at 90 days, 0.6% at 180 days, 0.4% at 270 days, and 0.1% at 365 days after the surgery. Surgery was strongly associated with postoperative persistent opioid use at day 90 (OR 3.67, 95% CI, 3.43 -3.94, p < 0.001), at day 180 (OR 2.85, 2.67 -3.12, p < 0.001), at day 270 (OR 2.63, 2.38 -2.91, p < 0.001) and at day 365 (OR 2.11, 1.77 -2.51, p < 0.001) compared to non-surgical controls. In risk factor analysis, being male and single were associated with persistent opioid use at earlier time points (90 and 180 days), while hepatitis C and preoperative benzodiazepine use were associated with persistent opioid use at later time points (270 and 365 days). Conclusions: Many surgeries or invasive procedures are associated with an increased risk of persistent postoperative opioid use. The postoperative period is dynamic and the risk factors change with time. Copyright 2020
  • Application of low dose pancreas perfusion CT combined with enhancement scanning in diagnosis of pancreatic neuroendocrine tumors

    Wan, Y.; Hao, H.; Meng, S.; Li, Z.; Yu, F.; Meng, chi; Chao, Q.; Gao, J. (Elsevier B.V., 2020-11-01)
    Purpose: To explore the diagnostic value of pancreatic perfusion CT combined with contrast-enhanced CT in one-time scanning (PCECT) in pancreatic neuroendocrine tumors (PNETs) and to evaluate the difference of perfusion parameters between different grades of PNETs. Materials and methods: From October 2016 to December 2018, forty consecutive patients with histopathological-proven PNETs were identified retrospectively that received PCECT for the preoperative PNETs evaluation. Two board certified radiologists who were blinded to the clinical data evaluated the images independently. The image characters of PNETs vs. tumor-free pancreatic parenchymal and different grades of PNETs were analyzed. Results: One-time PCECT scanning had a detection rate of 89.1% for PNETs, which was higher than the detection accuracy of the perfusion CT only (83.6%). The perfusion parameters of PNETs including blood volume (BV), blood flow (BF), mean slope of increase (MSI), and capillary surface permeability (PS) were significantly increased than those of tumor-free pancreatic parenchyma (p < 0.05, respectively). For differential comparison between grade I (G1) and grade II (G2) tumors, the parameters of BF and impulse residue function (IRF) of tumor tissue were significantly higher in the G2 tumors (p < 0.05, for both). In this study, the total radiation dose of the whole PCECT scan was 16.241 ±2.289 mSv. Conclusion: The one-time PCECT scan may improve the detection of PNETs according to morphological features and perfusion parameters with a relative small radiation dose. The perfusion parameters of BF and IRF may be used to help distinguish G1 and G2 tumors in the preoperative evaluation. Copyright 2020 IAP and EPC
  • Real-time assessment of daytime sleepiness in drivers with multiple sclerosis

    Devos, H.; Alissa, N.; Lynch, S.; Sadeghi, M.; Akinwuntan, A.E.; Siengsukon, C. (Elsevier B.V., 2020-10-31)
    Background: Daytime sleepiness is a common symptom of multiple sclerosis (MS) that may jeopardize safe driving. Our aim was to compare daytime sleepiness, recorded in real-time through eyelid tracking, in a simulated drive between individuals with MS (iwMS) and healthy controls. Methods: Fifteen iwMS (age = median (Q1 - Q3), 55 (50 - 55); EDSS = 2.5 (2 - 3.5); 12 (80%) female) were matched for age, sex, education, and cognitive status with 15 controls. Participants completed self-reported fatigue and sleepiness scales including the Modified Fatigue Impact Scale (MFIS), Pittsburg Sleep Quality Inventory (PSQI), and Epworth Sleepiness Scale (ESS). Percentage of eyelid closure (PERCLOS) was extracted from a remote eye tracker while completing a simulated drive of 25 min. Results: Although iwMS reported more symptoms of fatigue (MFIS, p = 0.003) and poorer sleep quality (PSQI, p = 0.008), they did not report more daytime sleepiness (ESS, p = 0.45). Likewise, there were no differences between groups in real-time daytime sleepiness, indexed by PERCLOS (p = 0.82). Both groups exhibited more real-time daytime sleepiness as they progressed through the drive (time effect, p < 0.0001). The interaction effect of group*time (p = 0.05) demonstrated increased symptoms of daytime sleepiness towards the end of the drive in iwMS compared to controls. PERCLOS correlated strongly (Spearman ρ = 0.76, p = 0.001) with distance out of lane in iwMS. Conclusion: IwMS show exacerbated symptoms of daytime sleepiness during a monotonous, simulate drive. Future studies should investigate the effect of MS on daytime sleepiness during real-world driving. Copyright 2020
  • Vasculogenic Erectile Dysfunction: The Impact of Diet and Lifestyle

    Ostfeld, R.J.; Allen, K.E.; Aspry, K.; Brandt, E.J.; Spitz, A.; Liberman, J.; Belardo, D.; O'Keefe, J.H.; Aggarwal, M.; Miller, M.; et al. (Elsevier Inc., 2020-11-20)
    Vasculogenic erectile dysfunction has been aptly called the "canary in the coal mine" for cardiovascular disease because it almost always precedes other manifestations of atherosclerotic cardiovascular disease, including myocardial infarction and stroke. It is common, associated with the presence of modifiable cardiovascular risk factors, and impacted by diet and lifestyle choices. This concise review provides an update on the use of dietary and other lifestyle interventions to improve vasculogenic erectile dysfunction and atherosclerotic cardiovascular disease. Copyright 2020 Elsevier Inc.

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