DOCSLIB.ORG

The Third International Consensus Guidelinesthe on Management of Cytomegalovirus in Cincinnati, OH

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Third International Consensus Guidelinesthe on Management of Cytomegalovirus in Cincinnati, OH Original Clinical ScienceçGeneral The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation Camille N. Kotton, MD,1 Deepali Kumar, MD,2 Angela M. Caliendo, MD, PhD,3 Shirish Huprikar, MD,4 01/28/2019 on BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3pzrw1VmaZXQ+S1X5qzIxw8+AIlXMhR5CNF7trXzV+w4= by https://journals.lww.com/transplantjournal from Downloaded Sunwen Chou, MD,5 Lara Danziger-Isakov, MD, MPH,6 and Atul Humar, MD7 Downloaded on behalf of the The Transplantation Society International CMV Consensus Group from https://journals.lww.com/transplantjournal Abstract: Despite recent advances, cytomegalovirus (CMV) infections remain one of the most common complications affecting solid organ transplant recipients, conveying higher risks of complications, graft loss, morbidity, and mortality. Research in the field and development of prior consensus guidelines supported by The Transplantation Society has allowed a more standardized ap- proach to CMV management. An international multidisciplinary panel of experts was convened to expand and revise evidence and expert opinion-based consensus guidelines on CMV management including prevention, treatment, diagnostics, immunology, drug resistance, and pediatric issues. Highlights include advances in molecular and immunologic diagnostics, improved understanding by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3pzrw1VmaZXQ+S1X5qzIxw8+AIlXMhR5CNF7trXzV+w4= of diagnostic thresholds, optimized methods of prevention, advances in the use of novel antiviral therapies and certain immuno- suppressive agents, and more savvy approaches to treatment resistant/refractory disease. The following report summarizes the updated recommendations. (Transplantation 2018;102: 900–931) he past 5 years has seen exciting advances related to the convened in 2008 and 2012 by The Infectious Diseases Sec- Tunderstanding, diagnosis, and treatment of Cytomega- tion of The Transplantation Society to develop consensus lovirus (CMV). We currently stand on the cusp of moderniz- guidelines on CMV management, subsequently published ing the management of CMV infection posttransplant. in 20104 and 2013.5 Topics included diagnostics, immunol- Despite these advances, CMV remains one of the most com- ogy, prevention, treatment, resistance, and pediatrics. Given mon complications affecting solid organ transplant recipients numerous recent advances in the field, a third meeting of ex- (SOTR), still befitting the designation: “a transplantation perts was convened in March 2017 to update these guidelines. troll.”1 In addition to the direct effects of CMV infection The expert panel rated the quality of evidence on which and disease, there are “indirect effects,” both general and recommendations are based by following a process used in transplant-specific, and higher rates of all types of infection, the development of other guidelines, including those by the graft loss, morbidity, and mortality.2,3 A panel of experts on Infectious Diseases Society of America. The Grading of Rec- CMV and solid organ transplantation (SOT) was previously ommendations Assessment, Development and Evaluation Received 15 January 2018. Revision received 12 March 2018. from Roche, Shire, Qiagen, Oxford Immunotec as well as consultancy fees from Accepted 13 March 2018. Qiagen and Oxford Immunotec. S.C. performed contracted CMV phenotyping on research for Merck and Shire. S.H. and L.D.-I. have no conflicts to declare. A.H. 1 01/28/2019 Transplant and Immunocompromised Host Infectious Diseases Infectious Dis- received research support from Qiagen, Astellas and Roche. eases Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA. All authors participated in the consensus meeting, review and summary of available data, and in the writing of the article. 2 Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada. The CMV Consensus Conference was organized by the Infectious Diseases Section of The Transplantation Society. Independent, nonrestricted grants from Hoffman 3 Rhode Island Hospital, Providence, RI. LaRoche, Merck, Oxford Immunotec, Qiagen, Shire, CSL Behring, Lophius 4 Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. Biosciences, Chimerix, Roche Molecular Systems, and Abbott Laboratories made 5 Division of Infectious Diseases, Oregon Health & Science University, Portland, OR. this conference possible. At no time did the funding sources have input into the list of attendees, discussion, or content. 6 Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. Correspondence: Camille N. Kotton, MD, Transplant and Immunocompromised Host Infectious Diseases Infectious Diseases Division, Massachusetts General 7 Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Hospital, Harvard Medical School 55 Fruit Street, Cox 5, Boston, MA 02114. Canada. ([email protected]). C.N.K. received funding for serving on scientific advisory boards for Roche Molecular Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. and Merck; adjudication boards for Astellas, Merck, and Shire; and consultancy fees from Qiagen and Oxford Immunotec. A.M.C. received funding for serving on a ISSN: 0041-1337/18/10206-0900 scientific advisory board for Roche Molecular. D.K. has received research grants DOI: 10.1097/TP.0000000000002191 900 www.transplantjournal.com Transplantation ■ June 2018 ■ Volume 102 ■ Number 6 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. © 2018 Wolters Kluwer Kotton et al 901 system allows for a systematic weighting of the strength of As in our prior versions, the term deoxyribonucleic acid recommendation (eg, “high, moderate, low, very low”)and in blood (DNAemia) will be used instead of viremia, to re- quality of evidence (eg, “strong, weak”)(Table1).6-10,13 flect the detection of CMV DNA in blood or plasma (whether We used the following definitions, consistent with the actively replicating virus or not). For accuracy, the phrases American Society of Transplantation and the CMV Drug Devel- “viral load” or “quantitative nucleic acid amplification opment Forum recommendations for use in clinical trials14,15: testing (QNAT)” are used instead of “polymerase chain reaction (PCR).” • CMV infection: evidence of CMV replication regardless of symptoms (differs from latent CMV); “defined as virus isola- tion or detection of viral proteins (antigens) or nucleic acid DIAGNOSTICS in any body fluid or tissue specimen”15 Pretransplant Testing • CMV disease: evidence of CMV infection with attributable symptoms. CMV disease can be further categorized as a viral Given that the CMV serostatus of donor and recipient syndrome (ie, fever, malaise, leukopenia, and/or thrombocy- (D/R) are key predictors of the risk of CMV after transplant topenia),orastissueinvasive(“end organ”) disease. and guide decisions on antiviral prophylaxis or preemptive TABLE 1. GRADE strength of recommendations and quality of the evidence6-12 Strength of recommendation Clarity of balance between desirable Methodological quality of supporting and quality of evidence and undesirable effects evidence (examples) Implications Strong recommendation, Desirable effects clearly outweigh Consistent evidence from well-performed Recommendation can apply to most patients high-quality evidence undesirable effects, or vice versa RCTs or exceptionally strong evidence in most circumstances. Further research is from unbiased observational studies unlikely to change our confidence in the estimate of effect Strong recommendation, Desirable effects clearly outweigh Evidence from RCTs with important Recommendation can apply to most patients moderate-quality undesirable effects, or vice versa limitations (inconsistent results, in most circumstances. Further research evidence methodological flaws, indirect, (if performed) is likely to have an important or imprecise) or exceptionally strong impact on our confidence in the estimate evidence from unbiased of effect and may change the estimate. observational studies Strong recommendation, Desirable effects clearly outweigh Evidence for at least 1 critical outcome Recommendation may change when low-quality evidence undesirable effects, or vice versa from observational studies, RCTs with higher-quality evidence becomes available. serious flaws or indirect evidence Further research (if performed) is likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Strong recommendation Desirable effects clearly outweigh Evidence for at least 1 critical outcome Recommendation may change when very-low-quality evidence undesirable effects, or vice versa from unsystematic clinical observations higher-quality evidence becomes available; (very rarely applicable) any estimate of effect for at least 1 critical or very indirect evidence outcome is very uncertain. Weak recommendation, Desirable effects closely balanced Consistent evidence from well-performed The best action may differ depending on high-quality evidence with undesirable effects RCTs or exceptionally strong evidence circumstances or patients or societal values. from unbiased observational studies Further research is unlikely to change our confidence in the estimate of effect. Weak recommendation, Desirable effects closely balanced Evidence from RCTs with important Alternative approaches likely to
Load more

Recommended publications
  • COMMISSION DE LA TRANSPARENCE Avis 5 Septembre 2018
    COMMISSION DE LA TRANSPARENCE Avis 5 septembre 2018 Date d’examen par la Commission : 20 juin 2018 L’avis de la commission de la Transparence adopté le 11 juillet 2018 a fait l’objet d’une audition le 5 septembre 2018. letermovir PREVYMIS 240 mg, comprimés pelliculés Boîte de 28 (CIP : 34009 301 272 3 0) PREVYMIS 240 mg, solution à diluer pour perfusion Boite de 1 (CIP : 34009 301 272 5 4) PREVYMIS 480 mg, comprimés pelliculés Boîte de 28 (CIP : 34009 301 272 4 7) PREVYMIS 480 mg, solution à diluer pour perfusion Boite de 1 (CIP : 34009 301 272 6 1) Laboratoire MSD France Code ATC J05AX18 (Antiviral) Motif de l’examen Inscription Sécurité Sociale (CSS L.162-17) pour les formes comprimés uniquement Listes concernées Collectivités (CSP L.5123-2) pour l’ensemble des présentations « PREVYMIS est indiqué dans la prophylaxie de la réactivation du cytomégalovirus (CMV) et de la maladie à CMV chez les adultes séropositifs au CMV receveurs [R+] d’une greffe allogénique de cellules Indication concernée souches hématopoïétiques (GCSH). Il convient de tenir compte des recommandations officielles concernant l’utilisation appropriée des agents antiviraux. » HAS - Direction de l'Evaluation Médicale, Economique et de Santé Publique 1/18 Avis3 SMR Important Compte tenu : - de la démonstration de l’efficacité de PREVYMIS en prophylaxie de la réactivation du CMV par rapport au placebo et notamment la diminution des instaurations de traitements préemptifs exposant les patients à une toxicité hématologique ou rénale importante, - de l’absence d’impact démontré
    [Show full text]
  • Subtherapeutic Posaconazole Prophylaxis in a Gastric Bypass Patient Following Hematopoietic Stem Cell Transplantation
    applyparastyle “fig//caption/p[1]” parastyle “FigCapt” CASE REPORT Subtherapeutic posaconazole prophylaxis in a gastric bypass patient following hematopoietic stem cell transplantation Emily A. Highsmith, PharmD, BCCCP, Department of Pharmacy, University Purpose. A case of invasive fungal infections (IFIs) with subtherapeutic of Texas MD Anderson Cancer Center, Houston, TX, USA posaconazole prophylaxis in a gastric bypass patient following hemato- poietic stem cell transplantation (HSCT) is reported. Downloaded from https://academic.oup.com/ajhp/article/78/14/1282/6245082 by BINASSS user on 15 July 2021 Vi P. Doan, PharmD, BCOP, Department of Pharmacy, University of Texas MD Anderson Cancer Center, Summary. A 52-year-old malnourished male with a medical history of Houston, TX, USA Roux-en-Y gastric bypass for obesity developed acute myelogenous leu- Todd W. Canada, PharmD, BCNSP, kemia and underwent allogeneic HSCT approximately 17 months later. He BCCCP, FASHP, FTSHP, FASPEN, was admitted 1 month after HSCT for failure to thrive and initiated on par- Department of Pharmacy, University of Texas MD Anderson Cancer Center, enteral nutrition due to worsening diarrhea and suspected gastrointestinal Houston, TX, USA graft-versus-host disease (GI GVHD). During admission, the patient was continued on daily oral posaconazole for antifungal prophylaxis and was found to have subtherapeutic posaconazole and deficient vitamin levels, likely secondary to his gastrojejunostomy and increased gastric transit time. The oral posaconazole was altered to twice-daily dosing in an effort to increase serum drug levels and prevent IFIs. Conclusion. Patients with a history of gastric bypass are at increased risk for malabsorption of oral posaconazole and nutrients, especially following HSCT with suspected GI GVHD.
    [Show full text]
  • R&D Briefing 76
    The Impact of Recent Regulatory Developments on the Mexican Therapeutic Landscape Access to innovative medicines is key to El acceso a medicamentos innovadores es clave para improving overall population health, reducing mejorar la salud de toda la población, para reducir los hospitalisation time and decreasing morbidity and tiempos de hospitalización, la morbilidad y la mortalidad mortality. An efficient regulatory process can be de un país. Un proceso regulatorio eficiente tiene un reflected in measurable positive health impacts; impacto positivo medible en la salud, y por el contrario, conversely, activities that slow or impede acciones que retrasan o impiden la eficiencia regulatoria y regulatory efficiency and predictability can be su predictibilidad pueden ser perjudiciales. La parálisis detrimental. Recent developments in the Mexican reciente del Sistema regulatorio mexicano respecto a la regulatory system for the assessments of evaluación de nuevos medicamentos innovadores innovative new products have had a negative conlleva un impacto negativo en la salud de la población impact on Mexican public health. mexicana. This Briefing addresses the impact of suspending Este informe analiza el impacto de la suspensión de las the activities of the New Molecules Committee actividades del Comité de Moléculas Nuevas (NMC, por (NMC) on the Mexican therapeutic landscape. sus siglas en inglés) sobre el horizonte terapéutico de First, we compared the way that “new medicines” México. En primer lugar, comparamos la definición de are defined within the context of the Mexican nuevos medicamentos según el contexto regulatorio regulatory system, with definitions used by mexicano con las definiciones adoptadas por otras comparable regulators and health organisations. agencias reguladoras u organizaciones de salud del We have also investigated the extent to which mundo.
    [Show full text]
  • SAMHD1 . . . and Viral Ways Around It
    viruses Review SAMHD1 . and Viral Ways around It Janina Deutschmann and Thomas Gramberg * Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; [email protected] * Correspondence: [email protected] Abstract: The SAM and HD domain-containing protein 1 (SAMHD1) is a dNTP triphosphohydrolase that plays a crucial role for a variety of different cellular functions. Besides balancing intracellular dNTP concentrations, facilitating DNA damage repair, and dampening excessive immune responses, SAMHD1 has been shown to act as a major restriction factor against various virus species. In addition to its well-described activity against retroviruses such as HIV-1, SAMHD1 has been identified to reduce the infectivity of different DNA viruses such as the herpesviruses CMV and EBV, the poxvirus VACV, or the hepadnavirus HBV. While some viruses are efficiently restricted by SAMHD1, others have developed evasion mechanisms that antagonize the antiviral activity of SAMHD1. Within this review, we summarize the different cellular functions of SAMHD1 and highlight the countermeasures viruses have evolved to neutralize the restriction factor SAMHD1. Keywords: SAMHD1; restriction factor; viral antagonism; HIV; herpesviruses; viral kinases; Vpx; dNTP hydrolase; viral interference 1. The dNTPase SAMHD1 The SAM and HD domain-containing protein 1 (SAMHD1) is a ubiquitously expressed Citation: Deutschmann, J.; deoxynucleotide triphosphohydrolase (dNTPase) of 626 amino acids (Figure1). In general, Gramberg, T. SAMHD1 . and Viral sterile alpha motif (SAM) domains have been shown to mediate protein–protein interaction Ways around It. Viruses 2021, 13, 395. or nucleic acid binding; however, its function in SAMHD1 is still unclear. The enzymatically https://doi.org/10.3390/v13030395 active HD domain, defined by two pairs of histidine and aspartate residues in its active center, on the other hand is essential for retroviral restriction and tetramerization of the Academic Editor: Sébastien Nisole protein [1–3].
    [Show full text]
  • 11-2018 BMT Pharmacists Johnson FINAL 2 12 18
    2018 BMT Pharmacists Conference Infection Prophylaxis in the HCT patient Melissa D. Johnson, PharmD, AAHIVP Associate Professor of Medicine Duke University Medical Center Liaison Clinical Pharmacist Duke Antimicrobial Stewardship Outreach Network Durham, North Carolina [email protected] @idpharmacist Disclosures • Research grants: Merck, Charles River Laboratories Objectives • Assess the factors influencing risk of infection in hematopoietic cell transplant recipients • Compare and contrast current, recently approved and emerging antimicrobials for prophylaxis in hematopoietic cell transplant recipients • Discuss recent studies evaluating antimicrobials for prophylaxis in hematopoietic cell transplant recipients • Identify important monitoring parameters and supportive strategies for prophylaxis in hematopoietic cell transplant recipients Hematopoietic Cell Transplantation Transplant Variables and Infection Risk • Underlying disease Pre-Tx Stem cells • Type of transplant Therapy +/- GVHD Autologous, Allogeneic • HLA matching Conditioning • Conditioning regimen Engraftment • Source of stem cells • Graft manipulation • Graft versus host disease • Donor & recipient age Bacterial Viruses Fungal INFECTIOUS PATHOGENS Respiratory Pneumocystis Viruses Other Case Question 1 • 37-year-old male with AML Initial presentation: • 45,000 WBC, normal cytogenetics, FLT3/ITD genes (+), NPM1 (-) Treatment plan: Standard induction followed by allogeneic hematopoietic peripheral blood stem-cell transplant • Which of the following pathogens is he at greatest
    [Show full text]
  • DMD #9209 1 N-Methylpurine DNA Glycosylase and 8-Oxoguanine
    DMD Fast Forward. Published on March 24, 2006 as DOI: 10.1124/dmd.105.009209 DMD FastThis article Forward. has not beenPublished copyedited on and March formatted. 24, The 2006 final version as doi:10.1124/dmd.105.009209 may differ from this version. DMD #9209 N-methylpurine DNA glycosylase and 8-oxoguanine DNA glycosylase metabolize the antiviral nucleoside 2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole Philip L. Lorenzi1, Christopher P. Landowski2, Andrea Brancale, Xueqin Song, Leroy B. Townsend, John C. Drach and Gordon L. Amidon. Department of Pharmaceutical Sciences (P.L.L., C.P.L., X.S., G.L.A.) and Medicinal Chemistry (L.B.T., J.C.D.), College of Pharmacy, and Department of Biologic and Downloaded from Materials Sciences (J.C.D.), School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA; and Welsh School of Pharmacy (A.B.), Cardiff University, Wales, UK. dmd.aspetjournals.org at ASPET Journals on September 24, 2021 1 Copyright 2006 by the American Society for Pharmacology and Experimental Therapeutics. DMD Fast Forward. Published on March 24, 2006 as DOI: 10.1124/dmd.105.009209 This article has not been copyedited and formatted. The final version may differ from this version. DMD #9209 Running Title: Nucleoside drug metabolism by DNA repair enzymes Text pages: 19 Tables: 4 Figures: 3 References: 43 Words in Abstract: 180 Words in Introduction: 464 Words in Discussion: 1433 Abbreviations: BDCRB, 2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole; TCRB, 2,5,6-trichloro-1-(β-D-ribofuranosyl)benzimidazole;
    [Show full text]
  • Novel Therapeutics for Epstein–Barr Virus
    molecules Review Novel Therapeutics for Epstein–Barr Virus Graciela Andrei *, Erika Trompet and Robert Snoeck Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium; [email protected] (E.T.); [email protected] (R.S.) * Correspondence: [email protected]; Tel.: +32-16-321-915 Academic Editor: Stefano Aquaro Received: 15 February 2019; Accepted: 4 March 2019; Published: 12 March 2019 Abstract: Epstein–Barr virus (EBV) is a human γ-herpesvirus that infects up to 95% of the adult population. Primary EBV infection usually occurs during childhood and is generally asymptomatic, though the virus can cause infectious mononucleosis in 35–50% of the cases when infection occurs later in life. EBV infects mainly B-cells and epithelial cells, establishing latency in resting memory B-cells and possibly also in epithelial cells. EBV is recognized as an oncogenic virus but in immunocompetent hosts, EBV reactivation is controlled by the immune response preventing transformation in vivo. Under immunosuppression, regardless of the cause, the immune system can lose control of EBV replication, which may result in the appearance of neoplasms. The primary malignancies related to EBV are B-cell lymphomas and nasopharyngeal carcinoma, which reflects the primary cell targets of viral infection in vivo. Although a number of antivirals were proven to inhibit EBV replication in vitro, they had limited success in the clinic and to date no antiviral drug has been approved for the treatment of EBV infections. We review here the antiviral drugs that have been evaluated in the clinic to treat EBV infections and discuss novel molecules with anti-EBV activity under investigation as well as new strategies to treat EBV-related diseases.
    [Show full text]
  • Hinge Region in DNA Packaging Terminase Pul15 of Herpes Simplex Virus: a Potential Allosteric Target for Antiviral Drugs
    Louisiana State University LSU Digital Commons Faculty Publications School of Renewable Natural Resources 10-1-2019 Hinge Region in DNA Packaging Terminase pUL15 of Herpes Simplex Virus: A Potential Allosteric Target for Antiviral Drugs Lana F. Thaljeh Louisiana State Univ, Dept Biol Sci, [email protected] J. Ainsley Rothschild Louisiana State Univ, Div Elect & Comp Engn, [email protected] Misagh Naderi Louisiana State Univ, Dept Biol Sci, [email protected] Lyndon M. Coghill Louisiana State Univ, Dept Biol Sci, [email protected] Follow this and additional works at: https://digitalcommons.lsu.edu/agrnr_pubs Part of the Biology Commons Recommended Citation Thaljeh, Lana F.; Rothschild, J. Ainsley; Naderi, Misagh; and Coghill, Lyndon M., "Hinge Region in DNA Packaging Terminase pUL15 of Herpes Simplex Virus: A Potential Allosteric Target for Antiviral Drugs" (2019). Faculty Publications. 4. https://digitalcommons.lsu.edu/agrnr_pubs/4 This Article is brought to you for free and open access by the School of Renewable Natural Resources at LSU Digital Commons. It has been accepted for inclusion in Faculty Publications by an authorized administrator of LSU Digital Commons. For more information, please contact [email protected]. biomolecules Article Hinge Region in DNA Packaging Terminase pUL15 of Herpes Simplex Virus: A Potential Allosteric Target for Antiviral Drugs Lana F. Thaljeh 1, J. Ainsley Rothschild 1, Misagh Naderi 1, Lyndon M. Coghill 1,2 , Jeremy M. Brown 1 and Michal Brylinski 1,2,* 1 Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA; [email protected] (L.F.T.); [email protected] (J.A.R.); [email protected] (M.N.); [email protected] (L.M.C.); [email protected] (J.M.B.) 2 Center for Computation & Technology, Louisiana State University, Baton Rouge, LA 70803, USA * Correspondence: [email protected]; Tel.: +225-578-2791; Fax: +225-578-2597 Received: 10 September 2019; Accepted: 8 October 2019; Published: 12 October 2019 Abstract: Approximately 80% of adults are infected with a member of the herpesviridae family.
    [Show full text]
  • Where Do We Stand After Decades of Studying Human Cytomegalovirus?
    microorganisms Review Where do we Stand after Decades of Studying Human Cytomegalovirus? 1, 2, 1 1 Francesca Gugliesi y, Alessandra Coscia y, Gloria Griffante , Ganna Galitska , Selina Pasquero 1, Camilla Albano 1 and Matteo Biolatti 1,* 1 Laboratory of Pathogenesis of Viral Infections, Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; [email protected] (F.G.); gloria.griff[email protected] (G.G.); [email protected] (G.G.); [email protected] (S.P.); [email protected] (C.A.) 2 Complex Structure Neonatology Unit, Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; [email protected] * Correspondence: [email protected] These authors contributed equally to this work. y Received: 19 March 2020; Accepted: 5 May 2020; Published: 8 May 2020 Abstract: Human cytomegalovirus (HCMV), a linear double-stranded DNA betaherpesvirus belonging to the family of Herpesviridae, is characterized by widespread seroprevalence, ranging between 56% and 94%, strictly dependent on the socioeconomic background of the country being considered. Typically, HCMV causes asymptomatic infection in the immunocompetent population, while in immunocompromised individuals or when transmitted vertically from the mother to the fetus it leads to systemic disease with severe complications and high mortality rate. Following primary infection, HCMV establishes a state of latency primarily in myeloid cells, from which it can be reactivated by various inflammatory stimuli. Several studies have shown that HCMV, despite being a DNA virus, is highly prone to genetic variability that strongly influences its replication and dissemination rates as well as cellular tropism. In this scenario, the few currently available drugs for the treatment of HCMV infections are characterized by high toxicity, poor oral bioavailability, and emerging resistance.
    [Show full text]
  • List of Drugs Not Repackaged by Safecor Health
    Drugs Not Repackaged by Safecor Health The following tables list specific medications that are not repackaged by Safecor Health due to regulatory restrictions or specific manufacturer requirements. The items not repackaged are alphabetically listed below, both by brand name (table 1) and generic name (table 2). Please note: Safecor Health cannot repackage any beta lactam antibiotics (such as penicillins, amoxicillin and cephalosporins) or potent chemotherapeutic agents. Also, due to FDA restrictions, we cannot repackage half- or quarter-tabs, compounded or diluted drugs, powders, and ointments or creams. Safecor Health can repackage most hazardous drugs on the NIOSH list. Contact us for a complete list of hazardous drugs repackaged by Safecor Health. Table 1. Do Not Repackage Drugs Sorted Alphabetically by Brand Name Brand Name(s) Generic Name(s) Reason Item Cannot Be Repackaged Adrucil Fluorouracil Potent chemotherapy agent Aspirin and Extended-Release Specific manufacturer recommendations for very Aggrenox Dipyridamole limited expiration dating Albenza Albendazole Cost per dose prohibitive Alkeran Melphalan Potent chemotherapy agent Augmentin Amoxicillin and Clavulanate Potassium Safecor Health does not repackage this drug class Manufacturer states, "dispense in original container," Belsomra Suvorexant on the drug label Manufacturer states, "dispense in original container," Biktarvy Bictegravir, Emtricitabine and Tenofovir Alafenamide on the drug label Bion Tears Dextran, Hypromellose Ophthalmic Drops Sterile and unpreserved CeeNU Lomustine
    [Show full text]
  • Human Cytomegalovirus Primary Infection and Reactivation: Insights from Virion-Carried Molecules
    fmicb-11-01511 July 16, 2020 Time: 8:16 # 1 REVIEW published: 14 July 2020 doi: 10.3389/fmicb.2020.01511 Human Cytomegalovirus Primary Infection and Reactivation: Insights From Virion-Carried Molecules Yu-Qing Wang1,2 and Xiang-Yu Zhao1* 1 Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China, 2 PKU-THU Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China Human cytomegalovirus (HCMV), a ubiquitous beta-herpesvirus, is able to establish lifelong latency after initial infection. Periodical reactivation occurs after immunosuppression, remaining a major cause of death in immunocompromised patients. HCMV has to reach a structural and functional balance with the host at Edited by: its earliest entry. Virion-carried mediators are considered to play pivotal roles in viral Akio Adachi, adaptation into a new cellular environment upon entry. Additionally, one clear difference Kansai Medical University, Japan between primary infection and reactivation is the idea that virion-packaged factors are Reviewed by: Eain Anthony Murphy, already formed such that those molecules can be used swiftly by the virus. In contrast, SUNY Upstate Medical University, virion-carried mediators have to be transcribed and translated; thus, they are not readily United States Sarah Elizabeth Jackson, available during reactivation. Hence, understanding virion-carried
    [Show full text]
  • Innovationsreport 2019 Kurzfassung
    Innovationsreport 2019 Auswertungsergebnisse von Routinedaten der Techniker Krankenkasse aus den Jahren 2016 bis 2017 Herausgeber: Gerd Glaeske und Wolf‐Dieter Ludwig Erstellt mit freundlicher Unterstützung der Techniker Krankenkasse (TK) 2 Herausgeber Prof. Dr. Gerd Glaeske Prof. Dr. Wolf‐Dieter Ludwig Experten für ausgewählte Kapitel Prof. Dr. med. Manfred Anlauf, Bremerhaven Prof. Dr. med. Peter Berlit, Berlin Prof. Dr. med. Winfried V. Kern, Freiburg Prof. Dr. med. Joachim Labenz, Siegen Prof. Dr. med. Ulrich A. Müller, MSc, Jena Prof. Dr. med. Bruno Müller‐Oerlinghausen, Berlin Prof. Dr. med. Wolfgang Schramm, München Prof. Dr. med. Dieter Ukena, Bremen PD Dr. med. Tobias Weberschock, Frankfurt am Main Autoren der Wirkstoffkapitel Dr. Stanislava Dicheva‐Radev, Dörte Fuchs, Dr. Iris Hinneburg, Anja Lübs, André S. Morawetz, Lutz Muth, Saskia Ritter, Dr. Kristin Sauer unter Mitarbeit von Eleonora Durakovic, Friederike Höfel, Linda Jespersen, Linda Richter, Marle Wilhelm Anschrift: Universität Bremen, SOCIUM, Mary‐Somerville‐Str. 5, 28359 Bremen Aus Gründen der besseren Lesbarkeit wurde auf die Nennung beider geschlechtsspezifischer Formen verzichtet. Im Allgemeinen ist aber das jeweils andere Geschlecht ebenfalls gemeint. 3 4 Glossar ........................................................................................... 6 Vorwort zum Innovationsreport 2019 ........................................... 13 Zweites Vorwort zum Innovationsreport 2019 .............................. 15 1 Einleitung ...............................................................................
    [Show full text]