Washington University School Of Medicine Research Articles

A Randomized Trial Comparing Skin Antiseptic Agents at Cesarean Delivery

BackgroundPreoperative skin antisepsis has the potential to decrease the risk of surgical-site infection. However, evidence is limited to guide the choice of antiseptic agent at cesarean delivery, which is the most common major surgical procedure among women in the United States.MethodsIn this single-center, randomized, controlled trial, we evaluated whether the use of chlorhexidine–alcohol for preoperative skin antisepsis was superior to the use of iodine–alcohol for the prevention of surgical-site infection after cesarean delivery. We randomly assigned patients undergoing cesarean delivery to skin preparation with either chlorhexidine–alcohol or iodine–alcohol. The primary outcome was superficial or deep surgical-site infection within 30 days after cesarean delivery, on the basis of definitions from the Centers for Disease Control and Prevention.ResultsFrom September 2011 through June 2015, a total of 1147 patients were enrolled; 572 patients were assigned to chlorhexidine–alcohol and 575 to iodine–alcohol. In an intention-to-treat analysis, surgical-site infection was diagnosed in 23 patients (4.0%) in the chlorhexidine–alcohol group and in 42 (7.3%) in the iodine–alcohol group (relative risk, 0.55; 95% confidence interval, 0.34 to 0.90; P=0.02). The rate of superficial surgical-site infection was 3.0% in the chlorhexidine–alcohol group and 4.9% in the iodine–alcohol group (P=0.10); the rate of deep infection was 1.0% and 2.4%, respectively (P=0.07). The frequency of adverse skin reactions was similar in the two groups.ConclusionsThe use of chlorhexidine–alcohol for preoperative skin antisepsis resulted in a significantly lower risk of surgical-site infection after cesarean delivery than did the use of iodine–alcohol. (Funded by the National Institutes of Health and Washington University School of Medicine in St. Louis; ClinicalTrials.gov number, NCT01472549.)

Life as an early career researcher: interview with Catherine Martel.

Catherine Martel speaks to Francesca Lake, Managing Commissioning Editor: Catherine Martel obtained her PhD from the Université de Montréal and pursued a postdoctoral fellowship first at Mount Sinai School of Medicine in New York (NY, USA), then at Washington University School of Medicine in St Louis (MO, USA), and obtained the Junior Investigator Award for Women from the Arteriosclerosis, Thrombosis and Vascular Biology council of the American Heart Association. Her postdoctoral work is certainly groundbreaking and brings forward new considerations in the field: she discovered that the lymphatic vessel route, the network that runs in parallel with the blood vessels, is critical for removing cholesterol from multiple tissues, including the aortic wall. In 2013, she joined the Arteriosclerosis, Thrombosis and Vascular Biology Early Career Committee, eager to bring a Canadian perspective to the group and get involved in council activities. Since 2014, she is an Assistant Professor at the Department of Medicine at the Université de Montréal, and a research scientist at the Montreal Heart Institute. Her research program now focuses on characterizing the physiopathologic role of the lymphatics in the initiation, progression and regression of atherosclerosis. Basic and translational research will allow her team to identify the causes of lymphatic dysfunction, and eventually target potential therapeutic strategies aiming at improving lymphatic function at the different levels of the atherothrombotic disease. You can follow her laboratory at @LaboMartel_ICM.

Implementation of a Screening Program for Patients at Risk for Posttraumatic Stress Disorder.

INTRODUCTIONImplantable cardioverter defibrillator (ICD) recipients who suffer from posttraumatic stress disorder (PTSD) are known to be associated with significant cardiac-specific mortality. Clinical observations suggest that PTSD is frequently undetected in ICD recipients followed up at electrophysiology (EP) outpatient clinics. Early recognition of PTSD is important to reduce the risk of serious manifestations on patient outcomes.METHODSAll ICD recipients aged 19 years or older at the Washington University School of Medicine (WASHU) EP clinic, a large urban EP clinic, were invited to participate in the project. An informed consent letter with an attached primary care: posttraumatic stress disorder (PC: PTSD) survey was offered to the participants who met the inclusion criteria. Those who completed the survey were included in the project. Individuals with positive survey result were offered a referral to mental health services. Comparisons between PTSD and non-PTSD patients were done using a two-sample t-test for continuous variables. Using Fisher’s exact test, PTSD prevalence was compared to the study by Ladwig et al in which prevalence was determined as the proportion of patients with positive findings of PTSD (n = 38/147). All analyses were conducted using SAS v9.4. The proportion of patients having PTSD was determined and an exact 95% confidence interval was evaluated based on the binomial distribution.RESULTSUsing a convenience sample, 50 ICD recipients (33 males and 17 females) were enrolled. The project had a 30-day outcome period. Nine (18%) of the 50 participants had positive PC: PTSD findings and all these nine participants were referred to a mental health specialist. The current project demonstrated an 18% (9/50) PTSD prevalence rate when compared to a 26% (38/147) prevalence rate in the study by Ladwig et al (P = 0.34). Although this project did not demonstrate 20% PTSD prevalence rate, as hypothesized, the 18% PTSD prevalence rate is consistent with previous research.CONCLUSIONThe prevalence of PTSD noted in the current project is consistent with previous research and validates underrecognition of PTSD in ICD patients. Offering a referral to all ICD recipients at EP clinic visits with a positive PC: PTSD screening to a mental health specialist is an important step in reducing the risk of serious manifestations on patient outcomes.

2015 Presidential Address: 75 Years of Battling Diabetes--Our Global Challenge.

This address was delivered by Samuel Dagogo-Jack, MD, President, Medicine & Science, of the American Diabetes Association (ADA), at the Association’s 75th Scientific Sessions in Boston, MA, on 7 June 2015. Dr. Dagogo-Jack is a professor of medicine and the director of the Division of Endocrinology, Diabetes and Metabolism and the director of the Clinical Research Center at The University of Tennessee Health Science Center, Memphis, TN, where he holds the A.C. Mullins Endowed Chair in Translational Research. He has been an ADA volunteer since 1991 and has served on several national committees and chaired the Association’s Research Grant Review Committee. At the local level, he has served on community leadership boards in St. Louis, MO, and Tennessee. A physician-scientist, Dr. Dagogo-Jack’s current research focuses on the interaction of genetic and environmental factors in the prediction and prevention of prediabetes, diabetes, and diabetes complications. He is the principal investigator of the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study and also directs The University of Tennessee site for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) and the Diabetes Prevention Program (DPP)/DPP Outcomes Study (DPPOS). Dr. Dagogo-Jack earned his medical and research doctorate degrees from the University of Ibadan College of Medicine in Nigeria, holds a master’s of science from the University of Newcastle upon Tyne in England, and completed his postdoctoral fellowship training in metabolism at the Washington University School of Medicine in St. Louis in Missouri. A board-certified endocrinologist, Dr. Dagogo-Jack has been elected to the Association of American Physicians and is the 2015 recipient of the Banting Medal for Leadership from the ADA. The ADA and Diabetes Care thank Dr. Dagogo-Jack for his outstanding leadership and service to the Association.

Use of Post-Transplant Cyclophosphamide (PTCy) with Mycophenolate Mofetil and Tacrolimus in HLA Matched Allogeneic Hematopoietic Cell Transplant Is Safe and Associated with Acceptable Transplant Outcomes

Background: The use of post-transplantation cyclophosphamide (PTCy) as a single agent for graft-versus-host disease (GVHD) prophylaxis in HLA matched transplant patients has had varied results. Two recent studies at Johns Hopkins University noted favorable incidences of both GVHD and non-relapse mortality (NRM) in both matched related and unrelated donor allogeneic hematopoietic cell transplant (allo-HCT) recipients (Kanakry CG, et al, JCO, 2013 and Kanakry CG et al, Blood, 2014). In contrast to this data, a phase II study at MD Anderson reported higher rates of grade II-IV acute GVHD and NRM, with worse overall survival in patients receiving PTCy as the sole GVHD prophylaxis compared to their matched cohort receiving a calcineurin-inhibitor (CNI) and methotrexate (MTX) as immunosuppression (Alousi AM et al, BBMT, 2015). Another study in Australia had to be stopped for safety reasons due to high GVHD and NRM when using PTCy as sole GVHD prophylaxis (Bradstock KF, BBMT, 2015). There is no published data on the use of MMF plus tacrolimus in combination with PTCy in HLA matched allo-HCT recipients. We hypothesized that addition of MMF and Tacrolimus to PTCy in HLA matched allo-HCT recipients will lead to significantly improved transplant outcomes. To answer this question we retrospectively analyzed data from patients who received this regimen at a single institution.Methods. We performed a retrospective analysis of 31 HLA matched allo-HCT patients who received PTCy at 50 mg/m2 on days +3 and +4 in addition to MMF and tacrolimus immunosuppression from December 2012 till June 2015 at Washington University School of Medicine in Saint Louis. All of these patients received G-CSF mobilized peripheral blood grafts. Patients included AML (n=13), ALL (n=5), MDS (n=5), CML (n=2), aplastic anemia (n=2) and NHL (n=1), myelofibrosis (n=1). Twelve of the patients underwent a matched related donor (MRD) transplant and 19 underwent a matched unrelated donor (MUD) transplant. Two of the MUD transplants had a HLA match grade of 8 of 10 and the other 17 were a 10 out of 10 match. Twenty-eight of the patients received a graft collected via peripheral blood stem cell mobilization and the other three had a donor graft collected via bone marrow harvest. Cumulative incidence of aGVHD was estimated using Gray's sub-distribution method to account for death without aGVHD as a competing event, and the cumulative incidences of non-relapse mortality (NRM) and relapse were estimated treating each other as competing event, while OS was estimated using Kaplan-Meier limit method.Results: This regimen was associated with acceptable GVHD in our patients. Incidence of grade II-IV acute GVHD was 28% (21.3% for MRD; 31.5% for MUD) at day 100 and 28% at 1 year. Incidence of Grade III-IV acute GVHD was 13.5% at both 100 days and 1 year. Limited chronic GVHD was 25.9% and extensive GVHD was 14.8% at 1 year. Similarly we found acceptable NRM and relapse in these patients, NRM was 10.2% and 19.7% at 100 days and 1 year respectively and cumulative incidence of relapse at 100 days and 1 year were 17.8% and 29.0% respectively. Overall survival at 1 year for all patients was 52%.Summary: Here we report favorable results from a regimen combining MMF and Tacrolimus on PTCy platform in HLA matched MRD and MUD transplant recipients. Relatively low GVHD and NRM results are particularly encouraging in view of almost exclusive use of G-CSF mobilized T cell replete grafts with much higher T cell content. Though limited by the relatively small number of patients, our results suggest combining MMF plus Tacrolimus with PTCy platform in HLA matched allogeneic transplant patients is safe and associated with acceptable transplant outcomes. DisclosuresVij:Onyx: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Millennium: Honoraria, Speakers Bureau; BMS: Consultancy; Takeda: Consultancy, Research Funding; Novartis: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; Merck: Consultancy. Uy:Novartis: Research Funding. Abboud:Teva Pharmaceuticals: Research Funding; Gerson Lehman Group: Consultancy; Merck: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees. Schroeder:Celgene: Other: Azacitidine provided for this trial by Celgene; Incyte: Consultancy. Jacoby:Sunesis: Research Funding; Novo Nordisk: Consultancy.

Complement Regulatory Gene Mutations in Non-Renal Solid Organ Transplant Recipients with Post-Transplant Thrombotic Microangiopathy

▪Complement dysregulation is central to the pathogenesis of atypical hemolytic uremic syndrome (aHUS). Mutations in genes encoding complement regulatory proteins (CRPs) can be identified in 61% of aHUS patients (Fremeaux-Bacchi 2013). In hematopoietic stem cell transplant (HSCT) recipients, all 6 children who developed post-transplant thrombotic microangiopathy (PT-TMA) were found to have a mutation in complement factor (CF) H related genes and/or the presence of CFH autoantibodies. In contrast, 18 children without evidence of PT-TMA had no mutations detected suggesting a strong role for complement dysregulation in the development of PT-TMA (Jodele 2013). Similarly, 30% of renal transplant patients who develop de novo PT-TMA had a mutation identified in CFH and/or CFI related genes, which were lacking in matched transplanted controls (Le Quintrec 2008).In non-renal solid organ transplant (NRSOT) recipients, the role of complement in PT-TMA is less well-understood. A lack of established diagnostic criteria makes PT-TMA in NRSOT recipients difficult to recognize. The overall rate of renal failure (RF) in NRSOT recipients ranges from 7-21% (Ojo, NEJM 2003). RF is often attributed to endothelial damage triggered by calcineurin inhibitors (CNI), infection, or ischemia, all of which activate the alternative complement pathway. We propose a contributor to NRSOT related RF is PT-TMA, which develops in a subset of patients with underlying mutations in genes encoding CRPs.From January 2012-Novemeber 2013, 10 patients were clinically diagnosed with PT-TMA (8 small bowel (SB), 2 liver) and treated with eculizumab at our institution. The 7 patients remaining on therapy at 1 year underwent testing for mutations in genes encoding CRPs via a commercially available assay at Washington University School of Medicine in St Louis. Identified mutations are depicted in table 1.Table 1Gene MutationsPatient 1SBCFHR3-CFHR1 heterozygous deletion CFH: 2808G>T, 1204C>TCFI: 898A>GPatient 2SBC3: p.T647M (1940C>T) heterozygous CFH: 2808G>T, 1204C>T, 184G>A, CFI: 898A>G, 1217G>ATHBD: 1418C>TPatient 3LCFH: p.Y402H, 1204C>T, 184G>A CFI: 898A>GTHBD: 1418C>TPatient 4SBCFI: 898A>GPatient 5LCFHR3-CFHR1 heterozygous deletion CFI: 898A>GCFB:1693A>G, 95G>APatient 6SBCFB p.I242L (724A>C) heterozygous CFH: 184G>A, 1204C>TCFI: 898A>GPatient 7SBCFH: p.Y402H, 1204C>T, 184G>ACFI: 898A>GCF: Complement Factor, THBD: Thrombomodulin, SB: Small Bowel, L: LiverAll patients clinically diagnosed with PT-TMA had at least one non-synonymous mutation identified in genes encoding CRPs, which supports the role of complement dysregulation in the pathogenesis of PT-TMA in NRSOT patients. CFI898A>G, CFH1204C>T, and the combination of CFH1204C>T and CFH184G>A were found in 100%, 71%, and 57% of our patients, suggesting clinical significance. CFHR3-CFHR1 heterozygous deletion was seen in 29% of our cohort and has been correlated with an increased risk of aHUS and presence of CFH autoantibodies as reported in HSCT-TMA (Zipfel 2007). Two patients were heterozygous for either C3 p.T647M or CFB p.I242, which have been noted in aHUS cohorts (Schramm 2015; Noris 2010). Although seen in 35% of the normal population, CFH p.Y402H was observed in 29% of our cohort. Its presence has been reported to affect CFH related binding and has been associated with complement mediated disorders of the eye and kidney (Mullins 2011; Hageman 2005; Abrera-Abeleda 2006).The identification of one or more CRP mutations in NRSOT patients with PT-TMA strongly suggests they harbor a predisposition to an impaired ability to regulate complement. Upon exposure to complement activating stimuli, these individuals develop PT-TMA or more accurately termed aHUS. We previously linked spontaneous thrombosis, as the underlying cause for SB transplant, to an increased risk of PT-TMA. The 3 patients with spontaneous thrombosis as the etiology for SB transplant that were tested were found to have CRP mutations, supporting our hypothesis that SB ischemia may be the presenting feature of aHUS. To better define the underlying PT-TMA-related risks associated with CRP mutations, we propose a study involving pre-transplant screening of all NRSOT recipients with ongoing prospective evaluation for the development and clinical course of PT-TMA. DisclosuresBroome:Alexion Pharmaceuticals: Consultancy, Honoraria, Research Funding.

Editorial introductions

Current Opinion in Neurology was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of neurology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS S. Thomas CarmichaelS. Thomas CarmichaelS. Thomas Carmichael is a neurologist and neuroscientist in the Department of Neurology at the David Geffen School of Medicine at UCLA, USA. Dr Carmichael is Professor and Vice Chair in the Department, with active laboratory and clinical interests in stroke and neurorehabilitation and how the brain repairs from injury. He received his M.D. and Ph.D. degrees from Washington University School of Medicine, USA, in 1993 and 1994, and completed a neurology residency at Washington University School of Medicine, serving as Chief Resident. Dr Carmichael was a Howard Hughes Medical Institute postdoctoral fellow at UCLA from 1998 to 2001. He has been on the UCLA faculty since 2001. Dr Carmichael's laboratory studies the molecular and cellular mechanisms of neural repair after stroke and other forms of brain injury. This research focuses on the processes of axonal sprouting and neural stem cell and progenitor responses after stroke, and on neural stem cell transplantation. Dr Carmichael is an attending physician on the Neurorehabilitation and Stroke clinical services at UCLA. Dr Carmichael has published important papers on stroke recovery that have defined mechanisms of plasticity and repair. These include the fact that the stroke produces stunned circuits that limit recovery, but can be restored to normal functioning with newly applied experimental drugs. His work has identified a novel brain “growth program” that is activated by stroke and leads to the formation of new connections. These studies have also identified how this growth program changes with age, and how specific molecules in the aged brain block the formation of new connections and of recovery. This and other work has led to new directions in stroke therapeutics, including therapies with stem cell and tissue engineering applications. Dr Carmichael is in the midst of stroke stem cell development applications with the FDA and with biotechnology companies. Gabriella BottiniGabriella BottiniShe is full Professor of Psychobiology and Neuropsychology at the Psychology Section of the Brain and Behavioral Sciences Department of the University of Pavia and Honorary Senior Lecturer at the Institute of Neurology of London. She is also the Director of the Clinical and Forensic Neuropsychology Laboratory, the Neuroscience and Society Laboratory at the University of Pavia, and the Cognitive neuropsychology Centre at the Niguarda Ca’ Granda Hospital in Milan. She is member of a number of societies of Neuroscience (ISN, ESN, SINDEM, SINP, etc.), and of the steering committee of the European Association for Neuroscience and Law (EANL). Her research activity is focused on the physiological and anatomical correlates of human behavior including both, cognitive and emotional components in a healthy human brain and how they are disrupted in psychiatric and neurodegenerative disorders. She is also involved in a number of activities concerning the interplay between neuroscience, neuroethics and law. Matthias PreusserMatthias PreusserMatthias Preusser is a medical oncologist and Associate Professor of Medicine at the Medical University of Vienna, Austria. His work focusses on biomarkers and treatment of brain tumors. Dr Preusser serves as Coordinator of the Central Nervous System Tumors Unit of the Comprehensive Cancer Center Vienna (CCC-CNS) and he is a steering committee member of the European Organization for Research and Treatment of Cancer (EORTC) Brain Tumor Group. Dr Preusser has co-authored more than 150 scientific articles and the current edition of the World Health Organization (WHO) Brain Tumor Classification. He is the principle investigator of an international randomized clinical trial in recurrent high-grade meningioma. Patrick RothPatrick RothDr Patrick Roth is an Attending Physician at the Department of Neurology and the Coordinating Physician of the Brain Tumor Center at the University Hospital Zurich, Switzerland. He specializes in the interdisciplinary management of brain tumour patients. He is involved in various clinical trials and conducts preclinical research to develop novel therapeutic strategies, with a focus on immunotherapeutic approaches for brain tumour patients. His current research focuses are the mechanisms underlying glioma immune escape, novel approaches to enhance the immunogenicity of glioma cells, and the analysis of new compounds for anti-glioma therapy.

Obituary: Mitchell P. Fink

Mitchell P. Fink, MD (Fig. 1), one of the most inspiring and influential leaders in the field of intensive care medicine, died at 66 years of age on 17 November 2015 after being diagnosed this summer with an aggressive sarcoma. This devastating news has left many of us with a huge sense of loss and sadness. Fig. 1 Mitchell P. Fink Mitch graduated from the Washington University School of Medicine in St. Louis, MO, in 1976 and completed general surgery training at the National Naval Medical Center in Bethesda, MD, in 1981. Thereafter, he held faculty positions at the Bethesda Naval Center and the University of Massachusetts, where he worked as surgeon and intensivist. In 1992 he moved to the Harvard Medical School, eventually becoming the Johnson and Johnson Professor in Surgery and surgeon-in-chief at the Beth Israel Deaconess Medical Center. He moved to the University of Pittsburgh in 1999, where he subsequently became the inaugural chair of the Department of Critical Care Medicine. He founded several companies based on discoveries from his laboratory and, in 2007, left the university to oversee the formation of one of these ventures. In 2009 Mitch returned to academia, joining the faculty at University of California Los Angeles where he held the title of Professor of Surgery and Vice Chair for Critical Care. During his career, Mitch cared for thousands of patients with skill and compassion, amassed a great body of experimental and clinical research, trained and mentored hundreds of physicians and scientists, demonstrated wonderful entrepreneurship, and carved a vision of modern multidisciplinary critical care with lasting benefits for our entire field. For decades, academic medicine has praised the rare individual who excels as the so-called triple threat: teacher, clinician, and scientist. Mitch was all three and more, adding to these triple roles the rare gift of visionary leader in both academia and industry. I have never known anyone quite like Mitch. His extraordinary career began early with a first author paper in Nature while still in medical school. While working in Bethesda, he forged close relationships with the National Institutes of Health critical care group, conducting a number of seminal experimental studies that both helped to establish the utility of animal models to probe the host response to sepsis, trauma, and shock and to inform our current understanding of these syndromes. Later, Mitch would conduct pioneering work using cell-based models of organ dysfunction to tease out the cellular response to stress from hypoxia and endogenous and exogenous danger signals, exploring key concepts of mitochondrial dysfunction and dysoxia. In addition to his passion for experimental research, Mitch also conducted many highly cited clinical studies, co-wrote the Textbook of Critical Care, and served on the editorial boards of numerous journals including Critical Care, Critical Care Medicine, and Intensive Care Medicine. To all of his work, Mitch brought four enduring characteristics: knowledge, logic, creativity, and focus. He maintained an encyclopedic knowledge of the world, able to quote relevant papers, data, and information off the top of his head from a dizzyingly wide range of art, science, politics, and history. He also exercised crystal-clear logic, distilling the most complex problem into a series of simple steps, whether this was a complicated piece of basic science or a tough business decision facing a start-up biotechnology company. Having concisely summarized any problem, he then brought great creativity and inventiveness to probe and tackle its solution. Finally, he always kept a clear sense of purpose, making sure neither he nor his colleagues ever lost sight of the larger goals of advancing medical knowledge and saving lives. I came to know Mitch during his tenure in Pittsburgh when he oversaw one of the most prolific and successful eras in our history, serving as a wonderful mentor and colleague, and launching the first multidisciplinary department of critical care medicine in a US medical school. In our daily contact with Mitch, we saw not only his intellect and drive, but also his warmth, compassion, wit, and grace. His door was always open, ready to listen to everyone from senior colleagues to junior residents and new staff. He had words of kindness and advice to coach us through every disappointment and words of praise and respect for every accomplishment. For me, as for many, Mitch was unquestionably one of the most supportive and influential people we have ever known. Through both his words and actions, he taught us not just about medicine and science, but about life, relationships, honor, duty, and service. We have lost an immense presence. Mitch is survived by his wife, Judy, and children, Matt and Emily. We extend our deepest condolences to them. He will be deeply missed.

A histamine-independent itch pathway is required for allergic ocular itch

Non-histaminergic TRPA1 neural pathway is required for the development of allergic ocular itch. Pharmacological inhibition of TRPA1 channel can lead to novel therapeutic strategies to treat ocular itch in severe allergic conjunctivitis.

Dose Escalation Using a Hydrogel Spacer for Intensity Modulated Radiation Therapy in Prostate Cancer

Dose Escalation Using a Hydrogel Spacer for Intensity Modulated Radiation Therapy in Prostate Cancer W.R. Bosch, W. Straube, T.A. DeWees, N.F. Mariados, J.E. Sylvester, D.K. Shah, S. Kurtzman, S.H. Zimberg, and J.M. Michalski; Washington University School of Medicine, St. Louis, MO, Associated Medical Professionals of NY PLLC, Syracuse, NY, 21st Century Oncology, Fort Myers, FL, Cancer Care of Western New York, Cheektowaga, NY, Northern California Prostate Cancer Center, Campbell, CA, Advanced Radiation Centers of New York, Hauppauge, NY

Exposing the human virome.

As medicine advances, we have come to realize that viral infections early in life can still be playing out in our body decades later, long after the primary infection has ended. New research has indicated that viral infections can precipitate the onset of a diverse array of long-term illnesses, from Alzheimer disease to chronic fatigue syndrome and type 1 diabetes mellitus (1). With that in mind, clinicians are interested in understanding more about viral exposures and how viral infections affect the body over the longterm. “Technologies exist for rapid identification of diverse bacteria,” says Dr. Nima Mosammaparast, Assistant Professor of Pathology and Immunology at Washington University School of Medicine, who cites as an example MALDI-TOF mass spectrometry. However, he says, such rapid identification “is not the case for viral diagnostics.” Viral diagnostics search the body for only 1 hypothesized virus at a time, or screen for only limited panels. That is, until now. Researchers at Harvard Medical School, under the guidance of Dr. Steve Elledge, Professor of Genetics and Medicine, have brought together “an ingenious combination of different technologies: DNA microarray, phage display, and high-throughput sequencing,” says Mosammaparast, to assess the entire viral infection history of an organism—including current viral infections the immune system is processing—using just a single drop of blood. By all accounts, the tool, known as VirScan, has the potential to …

Researchers Move Closer to Targeted Drug Delivery to Brain

Researchers Move Closer to Targeted Drug Delivery to Brain

Plastic and Reconstructive Surgery: Approaches and Techniques

Ross D. Farhadieh, Neil W. Bulstrode, Sabrina Cugno, eds. Plastic and Reconstructive Surgery: Approaches and Techniques . Hoboken, NJ: Wiley-Blackwell, 2015. ISBN-10: 1118655427, ISBN-13: 978-1118655429. $399.95. ![Graphic][1] Plastic and Reconstructive Surgery: Approaches and Techniques is a single-volume comprehensive plastic surgery textbook that deftly navigates that delicate balance between simply summarizing the vast components of plastic surgery or burdening the reader with volumes of extensive detail. The book's 79 chapters are divided into nine sections covering the core topics of plastic surgery: “Basic Science and Principles,” “Integument,” “Pediatric Plastic Surgery and Congenital Disorders,” “Head and Neck Reconstruction,” “Breast,” “Trunk and Lower Limb,” “Upper Limb,” and “Aesthetic Surgery” (the ninth and final section is entitled “Military, Simulation Training, and Exams”). Each chapter follows a similar outline: relevant anatomy, classification, surgical options, case examples, and complications. The editors have assembled over 130 international authors, many of whom are recognized authorities in their subspecialty, to provide a truly global perspective of the field of plastic surgery. The book is true to its subtitle: Approaches and … Corresponding Author: Dr Keith E. Brandt, Washington University School of Medicine, Division of Plastic and Reconstructive Surgery, CB 8238, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. E-mail: brandtk{at}wustl.edu [1]: /embed/inline-graphic-1.gif

A conversation with Stuart Kornfeld.

Stuart Kornfeld, of Washington University School of Medicine, is best known for his research in glycobiology, in particular his work describing pathways involved in oligosaccharide biosynthesis, processing, and maturation. These actions are critical in mediating proper folding and transport of proteins. Kornfeld (Figure 1) also discovered how lysosomal enzymes are routed from where they are produced to where they are needed in lysosomes, which help rid cells of macromolecules. See the full interview on the JCI website (http://www.jci.org/videos/cgms) for more of Kornfeld’s stories about his first experiment, stuttering, and why St. Louis has such magnetism.

Quantitative Evaluation of the Community Research Fellows Training Program.

The community research fellows training (CRFT) program is a community-based participatory research (CBPR) initiative for the St. Louis area. This 15-week program, based on a Master in Public Health curriculum, was implemented by the Division of Public Health Sciences at Washington University School of Medicine and the Siteman Cancer Center. We measure the knowledge gained by participants and evaluate participant and faculty satisfaction of the CRFT program both in terms of meeting learning objectives and actively engaging the community in the research process. We conducted analyses on 44 community members who participated in the CRFT program and completed the baseline and follow-up knowledge assessments. Knowledge gain is measured by a baseline and follow-up assessment given at the first and final session. Additionally, pre- and post-tests are given after the first 12 sessions. To measure satisfaction, program evaluations are completed by both the participants and faculty after each topic. Mid-way through the program, a mid-term evaluation was administered to assess the program's community engagement. We analyzed the results from the assessments, pre- and post-tests, and evaluations. The CRFT participants' knowledge increased at follow-up as compared with baseline on average by a 16.5 point difference (p < 0.0001). Post-test scores were higher than pre-test scores for 11 of the 12 sessions. Both participants and faculty enjoyed the training and rated all session well. The CRFT program was successful in increasing community knowledge, participant satisfaction, and faculty satisfaction. This success has enhanced the infrastructure for CBPR as well as led to CBPR pilot projects that address health disparities in the St. Louis Greater Metropolitan Area.

Handle With Care

Handle With Care

Editorial introductions

Current Opinion in Ophthalmology was launched in 1990. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Ophthalmology is divided into nine sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Roy S. ChuckRoy S. ChuckRoy S. Chuck M.D., Ph.D. serves as Chairman and University Professor and holds the Paul Henkind Chair at the Albert Einstein College of Medicine, USA, and Montefiore Medical Center in New York City, USA. He previously held the Tom Clancy Professorship in Ophthalmology and was the Director of Refractive Surgery at the Wilmer Eye Institute of Johns Hopkins University, USA. A cornea and refractive surgery specialist, Dr Chuck has expertise in both the fields of complex corneal transplantation including ocular surface reconstruction, and laser techniques for refractive eye problems and has published, patented and lectured extensively throughout his career. Dr Chuck, a University of California, Berkeley, USA, trained engineer, graduated from the Columbia University College of Physicians and Surgeons, USA, where he received his M.D., Ph.D. degree. He then proceeded on to residency in the Department of Ophthalmology and Visual Sciences at the Washington University School of Medicine, USA, where he also served as faculty Chief Resident. He completed his fellowship training in cornea and refractive surgery at the Doheny Eye Institute of the University of Southern California, USA. Prior to joining Einstein, Dr Chuck served on the faculties of Ophthalmology and Engineering at Washington University, University of Southern California, University of California, Irvine and Johns Hopkins University. Jimmy K. LeeJimmy K. LeeJimmy K. Lee, M.D. is the Director of Refractive Surgery at Montefiore Medical Center in Bronx, NY, USA. He specializes in laser vision correction surgery, including LASIK, LASEK, PRK and PTK. His surgical expertise also includes complex cataract surgery, anterior segment reconstruction, and artificial cornea. Dr Lee's research interests are new technologies in refractive surgery and improving surgical techniques for endothelial keratoplasty (DSAEK and DMEK). A member of the American Academy of Ophthalmology and American Society of Cataract and Refractive Surgery, he has extensively lectured nationally and internationally on these topics. He is the former Director of the Cornea, Refractive Surgery, and External Diseases service at the Yale Eye Center, USA. A Phi Beta Kappa graduate from Johns Hopkins University, USA, Dr Lee obtained his medical degree from Cornell University Medical College, USA. Following his residency at Albert Einstein Montefiore Hospital, USA, he completed a fellowship in cornea, external diseases, and refractive surgery at the Wilmer Eye Institute of The Johns Hopkins Hospital and is a Diplomate of the American Board of Ophthalmology. Shahzad I. MianShahzad I. MianDr Shahzad I. Mian is an Associate Professor of Ophthalmology and Visual Sciences at the University of Michigan Medical School, USA, and holds the Terry J. Bergstrom Collegiate Professorship for Resident Education. He has been Director of the Residency training program since 2004, and serves as the Associate Chair for Education. In 2003 and 2012, he received the Bergstrom Teaching Award presented by ophthalmology residents. His research focuses on the role of lasers in corneal transplantation, keratoplasty techniques and clinical studies in refractive surgery. Dr Mian received the 2007 Anthony Adamis Award for Outstanding Research from the U-M Kellogg Eye Institute, USA, and the 2009 Achievement Award from the American Academy of Ophthalmology. He serves as the medical director of the Michigan Eye bank, is on the board of directors for the Cornea Society and the Program Director's Council of the Association of University Professors of Ophthalmology (AUPO). Since 2011, Dr Mian has represented The Cornea Society as its Councilor for the American Academy of Ophthalmology. He has 50 publications in peer reviewed journals and over 20 book chapters.

Fast-forwarding treatment for neurodegenerative disorders

Fast-forwarding treatment for neurodegenerative disorders

Plastic Surgery Review: A Study Guide for the In-Service, Written Board, and Maintenance of Certification Exams

Gregory E. Lakin, ed. Plastic Surgery Review: A Study Guide for the In-Service, Written Board, and Maintenance of Certification Exams . Paperback: 235 pages. Publisher: Thieme (December 30, 2014). Language: English; ISBN-10: 1604068361, ISBN-13: 978-1604068368; Price: $69.99. ![Graphic][1] As its title clearly states, this text is intended to be a succinct review of testable content for the plastic surgery In-Service, Written Board, and Maintenance of Certification examinations. It is intended for surgical residents, freshly trained plastic surgeons preparing for their written board examinations, and those approaching a 10-year maintenance of certification examination interval. The content is subdivided into 4 sections based on the In-Service examination: (1) Comprehensive Plastic Surgery, (2) Craniomaxillofacial, (3) Breast and Cosmetic Surgery, and (4) Hand and Lower Extremity Surgery. Altogether, there are 50 chapters to cover the breadth of plastic surgery in a “point form” manner. Each chapter is reviewed by an expert in the field to confirm that it is up-to-date and accurate. Pertinent references included at the end of each chapter permit further in-depth review as required. This text delivers on its goal of providing “high-yield” content in a simultaneously concise and comprehensive manner. The author list is impressive and diverse with “giants” in their respective … Corresponding Author: Dr Terence M. Myckatyn, Washington University School of Medicine, 1040 N. Mason, Suite 124, Saint Louis, MO 63141, USA. E-mail: myckatyn{at}wudosis.wustl.edu [1]: /embed/inline-graphic-1.gif

Cerebrospinal Fluid Markers of Neurodegeneration and Rates of Brain Atrophy in Early Alzheimer Disease.

Measures of neuronal loss are likely good surrogates for clinical and radiological disease progression in Alzheimer disease (AD). Cerebrospinal fluid (CSF) markers of neuronal injury or neurodegeneration may offer usefulness in predicting disease progression and guiding outcome assessments and prognostic decisions in clinical trials of disease-modifying therapies. Visinin-like protein 1 (VILIP-1) has demonstrated potential usefulness as a marker of neuronal injury in AD. To investigate the usefulness of CSF VILIP-1, tau, p-tau181, and Aβ42 levels in predicting rates of whole-brain and regional atrophy in early AD and cognitively normal control subjects over time. Longitudinal observational study of brain atrophy in participants with early AD and cognitively normal controls. Study participants had baseline CSF biomarker measurements and longitudinal magnetic resonance imaging assessments for a mean follow-up period of 2 to 3 years. Mixed linear models assessed the ability of standardized baseline CSF biomarker measures to predict rates of whole-brain and regional atrophy over the follow-up period. The setting was The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine in St Louis. Participants (mean age, 72.6 years) were individuals with a clinical diagnosis of very mild AD (n = 23) and cognitively normal controls (n = 64) who were enrolled in longitudinal studies of healthy aging and dementia. The study dates were 2000 to 2010. Correlations between baseline CSF biomarker measures and rates of whole-brain or regional atrophy in the AD and control cohorts over the follow-up period. Baseline CSF VILIP-1, tau, and p-tau181 levels (but not Aβ42 levels) predicted rates of whole-brain and regional atrophy in AD over the follow-up period. Baseline CSF VILIP-1 levels predicted whole-brain (P = .006), hippocampal (P = .01), and entorhinal (P = .001) atrophy rates at least as well as tau and p-tau181 in early AD. Cognitively normal controls whose CSF VILIP-1, tau, or p-tau181 levels were in the upper tercile had higher rates of whole-brain (P = .02, P = .003, and P = .02, respectively), hippocampal (P = .001, P = .01, and P = .02, respectively), and entorhinal (P = .007, P = .01, and P = .01, respectively) atrophy compared with those whose levels were in the lower 2 terciles. Cerebrospinal fluid VILIP-1 levels predict rates of whole-brain and regional atrophy similarly to tau and p-tau181 and may provide a useful CSF biomarker surrogate for neurodegeneration in early symptomatic and preclinical AD.