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Clinical Reviewer: [Joohee Lee ] STN: [125508/153 ]
Clinical Reviewer: [Joohee Lee ] STN: [125508/153 ] Application sBLA Type STN 125508/153 CBER February 1, 2016 Received Date PDUFA Goal December 1, 2016 Date Division / DVRPA /OVRR Office Priority Review No Reviewer Joohee Lee Name(s) Review October 6, 2016 Completion Date / Stamped Date Supervisory Concurrence Lucia Lee, M.D., Team Leader, CRB1 Jeff Roberts, M.D., Chief, CRB1 Applicant Merck Established Human Papillomavirus 9-valent Vaccine, Recombinant Name (Proposed) Gardasil 9 Trade Name Pharmacologic Vaccine Class Page i Clinical Reviewer: [Joohee Lee ] STN: [125508/153 ] Formulation(s), A 0.5 mL dose contains: including Recombinant virus-like particles (VLPs) of the major capsid (L1) Adjuvants, etc protein of HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58)* adsorbed on preformed aluminum-containing adjuvant (Amorphous Aluminum Hydroxyphosphate Sulfate or AAHS) *Amounts of HPV type L1 protein are as follows: 30 mcg/40mcg/60mcg/40mcg/20mcg/20mcg/20mcg/20mcg/20mcg, respectively. Dosage 0.5-mL suspension for intramuscular injection as a single-dose Form(s) and vial and prefilled syringe Route(s) of Administration Dosing Two-dose regimen: 0 and 6 to 12 months Regimen A 3- dose regimen (0, 2 and 6 months) is approved for use in individuals 9 through 26 years of age (STN 125508/0) Page ii Clinical Reviewer: [Joohee Lee ] STN: [125508/153 ] Indication(s) and Intended This supplement introduces a 2-dose regimen in addition to the Population(s) licensed 3-dose regimen. The intended population for the 2- dose regimen is girls and boys 9 through 14 years of age. -
Quantitative Analysis of Bcl-2 Expression in Normal and Leukemic Human B-Cell Differentiation
Leukemia (2004) 18, 491–498 & 2004 Nature Publishing Group All rights reserved 0887-6924/04 $25.00 www.nature.com/leu Quantitative analysis of bcl-2 expression in normal and leukemic human B-cell differentiation P Menendez1,2, A Vargas3, C Bueno1,2, S Barrena1,2, J Almeida1,2 M de Santiago1,2,ALo´pez1,2, S Roa2, JF San Miguel2,4 and A Orfao1,2 1Servicio General de Citometrı´a, Universidad de Salamanca, Salamanca, Spain; 2Departamento de Medicina and Centro de Investigacio´n del Ca´ncer, Universidad de Salamanca, Salamanca, Spain; 3Servicio de Inmunodiagno´stico, Departamento de Patologı´a Clı´nica, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru´, ; and 4Servicio de Hematologı´a, Hospital Universitario, Salamanca, Spain Lack of apoptosis has been linked to prolonged survival of results in the overexpression of the bcl-2 protein and it malignant B cells expressing bcl-2. The aim of the present represented the first clear example of a common step in study was to analyze the amount of bcl-2 protein expressed 9,10 along normal human B-cell maturation and to establish the oncogenesis mediated by decreased cell death. Currently, frequency of aberrant bcl-2 expression in B-cell malignancies. the exact antiapoptotic pathways through which bcl-2 exerts its In normal bone marrow (n ¼ 11), bcl-2 expression obtained by role are only partially understood, involving decreased mito- quantitative multiparametric flow cytometry was highly vari- chondrial release of cytochrome c, which in turn is required for þ À able: very low in both CD34 and CD34 B-cell precursors, high the activation of procaspase-9 and the subsequent initiation of in mature B-lymphocytes and very high in plasma cells. -
Chlamydia Trachomatis Infection Is Driven by Nonprotective Immune Cells That Are Distinct from Protective Populations
Pathology after Chlamydia trachomatis infection is driven by nonprotective immune cells that are distinct from protective populations Rebeccah S. Lijeka,b,1, Jennifer D. Helblea, Andrew J. Olivea,c, Kyra W. Seigerb, and Michael N. Starnbacha,1 aDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; bDepartment of Biological Sciences, Mount Holyoke College, South Hadley, MA 01075; and cDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605 Edited by Rafi Ahmed, Emory University, Atlanta, GA, and approved December 27, 2017 (received for review June 23, 2017) Infection with Chlamydia trachomatis drives severe mucosal immu- sequence identity, Chlamydia muridarum, the extent to which the nopathology; however, the immune responses that are required for molecular pathogenesis of C. muridarum represents that of Ct is mediating pathology vs. protection are not well understood. Here, unknown (6). Ct serovar L2 (Ct L2) is capable of infecting the we employed a mouse model to identify immune responses re- mouse upper genital tract when inoculated across the cervix into quired for C. trachomatis-induced upper genital tract pathology the uterus (7, 8) but it does not induce robust immunopathology. and to determine whether these responses are also required for This is consistent with the human disease phenotype caused by Ct L2, bacterial clearance. In mice as in humans, immunopathology was which disseminates to the lymph nodes causing lymphogranuloma characterized by extravasation of leukocytes into the upper genital venereum (LGV) and is not a major cause of mucosal immunopa- thology in the female upper genital tract (uterus and ovaries). tract that occluded luminal spaces in the uterus and ovaries. -
NCCN Guidelines for Patients Anal Cancer
NCCN GUIDELINES FOR PATIENTS® 2021 Anal Cancer Presented with support from: Available online at NCCN.org/patients Ü Anal Cancer It's easy to get lost in the cancer world Let NCCN Guidelines for Patients® be your guide 9 Step-by-step guides to the cancer care options likely to have the best results 9 Based on treatment guidelines used by health care providers worldwide 9 Designed to help you discuss cancer treatment with your doctors NCCN Guidelines for Patients® Anal Cancer, 2021 1 About National Comprehensive Cancer Network® NCCN Guidelines for Patients® are developed by the National Comprehensive Cancer Network® (NCCN®) NCCN Clinical Practice NCCN Guidelines NCCN Guidelines in Oncology for Patients (NCCN Guidelines®) 9 An alliance of leading 9 Developed by doctors from 9 Present information from the cancer centers across the NCCN cancer centers using NCCN Guidelines in an easy- United States devoted to the latest research and years to-learn format patient care, research, and of experience 9 For people with cancer and education 9 For providers of cancer care those who support them all over the world Cancer centers 9 Explain the cancer care that are part of NCCN: 9 Expert recommendations for options likely to have the NCCN.org/cancercenters cancer screening, diagnosis, best results and treatment Free online at Free online at NCCN.org/patientguidelines NCCN.org/guidelines and supported by funding from NCCN Foundation® These NCCN Guidelines for Patients are based on the NCCN Guidelines® for Anal Cancer, Version 1.2021 — February 16, 2021. © 2021 National Comprehensive Cancer Network, Inc. All rights reserved. -
Leptospirosis: a Waterborne Zoonotic Disease of Global Importance
August 2006 volume 22 number 08 Leptospirosis: A waterborne zoonotic disease of global importance INTRODUCTION syndrome has two phases: a septicemic and an immune phase (Levett, 2005). Leptospirosis is considered one of the most common zoonotic diseases It is in the immune phase that organ-specific damage and more severe illness globally. In the United States, outbreaks are increasingly being reported is seen. See text box for more information on the two phases. The typical among those participating in recreational water activities (Centers for Disease presenting signs of leptospirosis in humans are fever, headache, chills, con- Control and Prevention [CDC], 1996, 1998, and 2001) and sporadic cases are junctival suffusion, and myalgia (particularly in calf and lumbar areas) often underdiagnosed. With the onset of warm temperatures, increased (Heymann, 2004). Less common signs include a biphasic fever, meningitis, outdoor activities, and travel, Georgia may expect to see more leptospirosis photosensitivity, rash, and hepatic or renal failure. cases. DIAGNOSIS OF LEPTOSPIROSIS Leptospirosis is a zoonosis caused by infection with the bacterium Leptospira Detecting serum antibodies against leptospira interrogans. The disease occurs worldwide, but it is most common in temper- • Microscopic Agglutination Titers (MAT) ate regions in the late summer and early fall and in tropical regions during o Paired serum samples which show a four-fold rise in rainy seasons. It is not surprising that Hawaii has the highest incidence of titer confirm the diagnosis; a single high titer in a per- leptospirosis in the United States (Levett, 2005). The reservoir of pathogenic son clinically suspected to have leptospirosis is highly leptospires is the renal tubules of wild and domestic animals. -
What Is Anal Cancer?
cancer.org | 1.800.227.2345 About Anal Cancer Overview and Types If you've been diagnosed with anal cancer or are worried about it, you likely have a lot of questions. Learning some basics is a good place to start. ● What Is Anal Cancer? Research and Statistics See the latest estimates for new cases of anal cancer and deaths in the US and what research is currently being done. ● Key Statistics for Anal Cancer ● What’s New in Anal Cancer Research? What Is Anal Cancer? Anal cancer is a type of cancer that starts in the anus. Cancer starts when cells in the body begin to grow out of control. To learn more about how cancers start and spread, see What Is Cancer?1 Normal structure and function of the anus 1 ____________________________________________________________________________________American Cancer Society cancer.org | 1.800.227.2345 The anus is the opening at the lower end of the intestines. It's where the end of the intestines connect to the outside of the body. As food is digested, it passes from the stomach to the small intestine. It then moves from the small intestine into the main part of the large intestine (called the colon). The colon absorbs water and salt from the digested food. The waste matter that's left after going through the colon is known as feces or stool. Stool is stored in the last part of the large intestine, called the rectum. From there, stool is passed out of the body through the anus as a bowel movement. Gastrointestinal system (GI system) Structures of the anus The anus is connected to the rectum by the anal canal. -
SNF Mobility Model: ICD-10 HCC Crosswalk, V. 3.0.1
The mapping below corresponds to NQF #2634 and NQF #2636. HCC # ICD-10 Code ICD-10 Code Category This is a filter ceThis is a filter cellThis is a filter cell 3 A0101 Typhoid meningitis 3 A0221 Salmonella meningitis 3 A066 Amebic brain abscess 3 A170 Tuberculous meningitis 3 A171 Meningeal tuberculoma 3 A1781 Tuberculoma of brain and spinal cord 3 A1782 Tuberculous meningoencephalitis 3 A1783 Tuberculous neuritis 3 A1789 Other tuberculosis of nervous system 3 A179 Tuberculosis of nervous system, unspecified 3 A203 Plague meningitis 3 A2781 Aseptic meningitis in leptospirosis 3 A3211 Listerial meningitis 3 A3212 Listerial meningoencephalitis 3 A34 Obstetrical tetanus 3 A35 Other tetanus 3 A390 Meningococcal meningitis 3 A3981 Meningococcal encephalitis 3 A4281 Actinomycotic meningitis 3 A4282 Actinomycotic encephalitis 3 A5040 Late congenital neurosyphilis, unspecified 3 A5041 Late congenital syphilitic meningitis 3 A5042 Late congenital syphilitic encephalitis 3 A5043 Late congenital syphilitic polyneuropathy 3 A5044 Late congenital syphilitic optic nerve atrophy 3 A5045 Juvenile general paresis 3 A5049 Other late congenital neurosyphilis 3 A5141 Secondary syphilitic meningitis 3 A5210 Symptomatic neurosyphilis, unspecified 3 A5211 Tabes dorsalis 3 A5212 Other cerebrospinal syphilis 3 A5213 Late syphilitic meningitis 3 A5214 Late syphilitic encephalitis 3 A5215 Late syphilitic neuropathy 3 A5216 Charcot's arthropathy (tabetic) 3 A5217 General paresis 3 A5219 Other symptomatic neurosyphilis 3 A522 Asymptomatic neurosyphilis 3 A523 Neurosyphilis, -
Gonorrhea, Chlamydia, and Syphilis
2019 GONORRHEA, CHLAMYDIA, AND SYPHILIS AND CHLAMYDIA, GONORRHEA, Dedication TAG would like to thank the National Coalition of STD Directors for funding and input on the report. THE PIPELINE REPORT Pipeline for Gonorrhea, Chlamydia, and Syphilis By Jeremiah Johnson Introduction The current toolbox for addressing gonorrhea, chlamydia, and syphilis is inadequate. At a time where all three epidemics are dramatically expanding in locations all around the globe, including record-breaking rates of new infections in the United States, stakeholders must make do with old tools, inadequate systems for addressing sexual health, and a sparse research pipeline of new treatment, prevention, and diagnostic options. Lack of investment in sexual health research has left the field with inadequate prevention options, and limited access to infrastructure for testing and treatment have allowed sexually transmitted infections (STIs) to flourish. The consequences of this underinvestment are large: according to the World Health Organization (WHO), in 2012 there were an estimated 357 million new infections (roughly 1 million per day) of the four curable STIs: gonorrhea, chlamydia, syphilis, and trichomoniasis.1 In the United States, the three reportable STIs that are the focus of this report—gonorrhea, chlamydia, and syphilis—are growing at record paces. In 2017, a total of 30,644 cases of primary and secondary (P&S) syphilis—the most infectious stages of the disease—were reported in the United States. Since reaching a historic low in 2000 and 2001, the rate of P&S syphilis has increased almost every year, increasing 10.5% during 2016–2017. Also in 2017, 555,608 cases of gonorrhea were reported to the U.S. -
STD Glossary of Terms
STD 101 In A Box- STD Glossary of Terms Abstinence Not having sexual intercourse Acquired A disease of the human immune system caused by the Human Immunodeficiency Virus (HIV). HIV/AIDS represents the entire range of Immunodeficiency disease caused by the HIV virus from early infection to late stage Syndrome (AIDS) symptoms. Anal Intercourse Sexual contact in which the penis enters the anus. Antibiotic A medication that either kills or inhibits the growth of a bacteria. Antiviral A medication that either kills or inhibits the growth of a virus. A thinning of tissue modified by the location. In epidermal atrophy, the epidermis becomes transparent with a loss of skin texture and cigarette Atrophic paper-like wrinkling. In dermal atrophy, there is a loss of connective tissue and the lesion is depressed. A polymicrobial clinical syndrome resulting from replacement of the Bacterial Vaginosis normal hydrogen peroxide producing Lactobacillus sp. in the vagina with (BV) high concentrations of anaerobic bacteria. The common symptom of BV is abnormal homogeneous, off-white, fishy smelling vaginal discharge. Cervical Motion A sign found on pelvic examination suggestive of pelvic pathology; when Tenderness (CMT) movement of the cervix during the bimanual exam elicits pain. The lower, cylindrical end of the uterus that forms a narrow canal Cervix connecting the upper (uterus) and lower (vagina) parts of a woman's reproductive tract. The most common sexually transmitted bacterial infection in the U.S., caused by the bacteria Chlamydia trachomatis. Often no symptoms are present, especially in women. Untreated chlamydia can cause sterility, Chlamydia Pelvic Inflammatory Disease (PID), and increase the chances for life- threatening tubal pregnancies. -
Pathology of Anal Cancer
Pathology of Anal Cancer a b Paulo M. Hoff, MD, PhD , Renata Coudry, MD, PhD , a, Camila Motta Venchiarutti Moniz, MD * KEYWORDS Anal cancer Anal squamous intraepithelial neoplasia Squamous cell carcinoma Human papilloma virus (HPV) Molecular KEY POINTS Anal cancer is an uncommon tumor, squamous cell carcinoma (SCC) being the most frequent histology corresponding to 80% of all cases. Human papilloma virus (HPV) infection plays a key role in anal cancer development, en- coding at least three oncoproteins with stimulatory properties. SCC expresses CK5/6, CK 13/19, and p63. P16 is a surrogate marker for the presence of HPV genome in tumor cells. INTRODUCTION Anal cancer accounts for approximately 2.4% of gastrointestinal malignancies.1 Although anal cancer is a rare tumor, its frequency is increasing, especially in high- risk groups.2 Tumors in this location are generally classified as anal canal or anal margin. Squamous cell carcinoma (SCC) is the predominant type of tumor and shares many features with cervical cancer. Oncogenic human papilloma virus (HPV) infection plays a major role in both tumors.3 HIV infection is associated with a higher frequency of HPV-associated premalignant lesions and invasive tumors.4 Normal Anatomy of the Anus The anal canal is the terminal part of the large intestine and is slightly longer in male than in female patients. It measures approximately 4 cm and extends from the rectal ampulla (pelvic floor level) to the anal verge, which is defined as the outer open- ing of the gastrointestinal tract. The anal verge is at the level of the squamous- mucocutaneous junction with the perianal skin.5,6 The authors have nothing to disclose. -
Chlamydia Trachomatis and Chlamydia Pneumoniae Interaction with the Host: Latest Advances and Future Prospective
microorganisms Review Chlamydia trachomatis and Chlamydia pneumoniae Interaction with the Host: Latest Advances and Future Prospective Marisa Di Pietro 1,* , Simone Filardo 1 , Silvio Romano 2 and Rosa Sessa 1 1 Department of Public Health and Infectious Diseases, Section of Microbiology, University of Rome “Sapienza”, 00185 Rome, Italy; simone.fi[email protected] (S.F.); [email protected] (R.S.) 2 Cardiology, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; [email protected] * Correspondence: [email protected] Received: 15 April 2019; Accepted: 14 May 2019; Published: 16 May 2019 Abstract: Research in Chlamydia trachomatis and Chlamydia pneumoniae has gained new traction due to recent advances in molecular biology, namely the widespread use of the metagenomic analysis and the development of a stable genomic transformation system, resulting in a better understanding of Chlamydia pathogenesis. C. trachomatis, the leading cause of bacterial sexually transmitted diseases, is responsible of cervicitis and urethritis, and C. pneumoniae, a widespread respiratory pathogen, has long been associated with several chronic inflammatory diseases with great impact on public health. The present review summarizes the current evidence regarding the complex interplay between C. trachomatis and host defense factors in the genital micro-environment as well as the key findings in chronic inflammatory diseases associated to C. pneumoniae. Keywords: Chlamydia trachomatis; Chlamydia pneumoniae; host-pathogen interaction 1. Introduction Currently, there is a renewed research interest in Chlamydiae that cause a broad spectrum of pathologies of varying severity in human, mainly Chlamydia trachomatis and Chlamydia pneumoniae [1,2]. Advances in molecular biology and, in particular, the recent advent of metagenomic analysis as well as the development of a stable genomic transformation system in Chlamydiae have significantly contributed to expanding our understanding of Chlamydia pathogenesis [3–5]. -
HPV, Anal Dysplasia and Anal Cancer
HPV, anal dysplasia FACT and anal cancer SHEET Published 2016 Summary Anal cancer typically develops over a period of years, beginning with a precancerous condition called anal dysplasia. CONTACT US Anal dysplasia occurs when clusters of abnormal cells form by telephone lesions in the mucosa lining of the anal canal (between the 1-800-263-1638 anus and the rectum). The lesions typically form inside the anal 416-203-7122 canal or just outside the anal opening. by fax 416-203-8284 Although there are over 100 different types of the human papillomavirus (HPV), anal dysplasia is usually caused by certain by e-mail strains of HPV which can be transmitted sexually. HPV can shut [email protected] off the proteins that help prevent dysplasia and cancer cells from developing, therefore leading to HPV-associated diseases by mail such as anal dysplasia. 555 Richmond Street West Suite 505, Box 1104 It is difficult to screen for anal dysplasia since the lesions are Toronto ON M5V 3B1 not detectable by routine examinations. As a result, anal dysplasia is often not detected until it has developed into anal cancer, which can be difficult to treat depending on the severity. Specific screening tests can detect dysplasia or precancerous changes. If these precancers are treated, anal cancer may be prevented. Anal cancer is usually treated with radiation and chemotherapy or with surgery. Although anal dysplasia may be treated successfully, individuals with HIV are at increased risk of it recurring and may need to be monitored closely by a trained physician. Consistent condom use reduces, but does not eliminate, the risk of transmitting HPV.