Virginia Commonwealth University

About: Virginia Commonwealth University is a education organization based out in Richmond, Virginia, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 23822 authors who have published 49587 publications receiving 1787046 citations. The organization is also known as: VCU.

2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors.

Abstract: This is the fourth American Society of Colposcopy and Cervical Pathology (ASCCP)-sponsored consensus guidelines for management of cervical cancer screening abnormalities, after the original consensus conferences in 20011 and subsequent updates in 20062 and 2012.3 An interim guidance publication providing management recommendations for primary HPV screening was released in 2015.4 This document updates and replaces all previous guidance. The key difference between 2019 guidelines and previous versions is the change from primarily test results–based algorithms (e.g., “Colposcopy is recommended for patients with HPV-positive atypical squamous cells of undetermined significance [ASC-US], low-grade squamous intraepithelial lesion [LSIL],” etc.) to primarily “risk-based” guidelines (e.g., “Colposcopy is recommended for any combination of history and current test results yielding a 4.0% or greater probability of finding CIN 3+,” etc.). See Box 1 for essential changes. Tables of risk estimates for possible combinations of current screening test results and screening history (including unknown history) have been generated from a prospective longitudinal cohort of more than 1.5 million patients followed for more than a decade at Kaiser Permanente Northern California (KPNC). All KPNC estimates of risk underlying guideline decisions are detailed in the accompanying article by Egemen et al.5 The applicability of these risk estimates to other United States regions and populations has been confirmed in other data sets from screening programs and clinical trials.6 Many patients, especially those with minor abnormalities, can be managed by identifying their risk level using Tables 1A to 5B in Egemen et al5 and linking it to a recommended clinical action (return to routine screening, surveillance with repeat testing at 1- or 3-year intervals, colposcopy, or treatment). To facilitate use of these tables, the same information will be accessible via smartphone app (for purchase) and web (no cost) through http://www.asccp.org. Decision aids may facilitate use of the tables.7 Common abnormalities are managed using risk estimates outlined in Section E, and rare abnormalities are managed via the result-specific consensus recommendations outlined in Sections G-K. Box 1. Essential Changes From Prior Management Guidelines 1) Recommendations are based on risk, not results. Recommendations of colposcopy, treatment, or surveillance will be based on a patient's risk of CIN 3+ determined by a combination of current results and history (including unknown history). The same current test results may yield different management recommendations depending on the history of recent past test results. 2) Colposcopy can be deferred for certain patients. Repeat HPV testing or cotesting at 1 year is recommended for patients with minor screening abnormalities indicating HPV infection with low risk of underlying CIN 3+ (e.g., low-grade cytologic abnormalities after a documented negative screening HPV test or cotest). At the 1-year follow-up test, referral to colposcopy is recommended if results remain abnormal. 3) Guidance for expedited treatment is expanded (i.e., treatment without colposcopic biopsy). Expedited treatment was an option for patients with HSIL cytology in the 2012 guidelines; this guidance is now better defined. For nonpregnant patients 25 years or older, expedited treatment, defined as treatment without preceding colposcopic biopsy demonstrating CIN 2+, is preferred when the immediate risk of CIN 3+ is ≥60%, and is acceptable for those with risks between 25% and 60%. Expedited treatment is preferred for nonpregnant patients 25 years or older with high-grade squamous intraepithelial lesion (HSIL) cytology and concurrent positive testing for HPV genotype 16 (HPV 16) (i.e., HPV 16–positive HSIL cytology) and never or rarely screened patients with HPV-positive HSIL regardless of HPV genotype. Shared decision-making should be used when considering expedited treatment, especially for patients with concerns about the potential impact of treatment on pregnancy outcomes. 4) Excisional treatment is preferred to ablative treatment for histologic HSIL (CIN 2 or CIN 3) in the United States. Excision is recommended for adenocarcinoma in situ (AIS). 5) Observation is preferred to treatment for CIN 1. Treatment remains acceptable for patients with repeat diagnoses of CIN 1 persisting 2 years or more. 6) Histopathology reports based on Lower Anogenital Squamous Terminology (LAST)/World Health Organization (WHO) recommendations for reporting histologic HSIL should include CIN 2 or CIN 3 qualifiers, i.e., HSIL(CIN 2) and HSIL (CIN 3). 7) All positive HPV tests, regardless of genotype, should have additional reflex triage testing performed from the same laboratory specimen (e.g., reflex cytology). Additional testing from the same laboratory specimen is recommended because the findings may inform colposcopy practice. For example, those with HSIL cytology and concurrent positive testing for HPV genotype 16 qualify for expedited treatment. HPV 16 or 18 infections have the highest risk for CIN 3 and occult cancer, so additional evaluation (e.g., colposcopy with biopsy) is necessary even when cytology results are negative. If HPV 16 and 18 testing is positive, and additional laboratory testing of the same sample is not feasible, the patient should proceed directly to colposcopy. 8) Continued surveillance with HPV testing or cotesting at 3-year intervals for at least 25 years is recommended after treatment of histologic HSIL, CIN 2, CIN 3, or AIS. Continued surveillance at 3-year intervals beyond 25 years is acceptable for as long as the patient's life expectancy and ability to be screened are not significantly compromised by serious health issues. The 2012 guidelines recommended return to 5-year screening intervals and did not specify when screening should cease. New evidence indicates that risk remains elevated for at least 25 years, with no evidence that treated patients ever return to risk levels compatible with 5-year intervals. Surveillance with cytology alone is acceptable only if testing with HPV or cotesting is not feasible. Cytology is less sensitive than HPV testing for detection of precancer and is therefore recommended more often. Cytology is recommended at 6-month intervals when HPV testing or cotesting is recommended annually. Cytology is recommended annually when 3-year intervals are recommended for HPV or cotesting. 9) Human papilloma virus assays that are Food and Drug Administration (FDA)-approved for screening should be used for management according to their regulatory approval in the United States. (Note: all HPV testing in this document refers to testing for high-risk HPV types only). For all management indications, HPV mRNA and HPV DNA tests without FDA approval for primary screening alone should only be used as a cotest with cytology, unless sufficient, exceptionally rigorous data are available to support primary HPV testing in management. The minimum amount of data required to generate a recommendation will include the patient's age and current test results, as we recognize that previous screening history is often not known. Increased precision of management guidance will be possible if information is available on test results within the past 5 years and previous precancer treatment within the past 25 years.3 Current results and past history are designed to generate the patient's risk estimate from data tables.5 Risk estimates are available for the following clinical situations: abnormal screening test results with unknown history, abnormal screening test results with medical record documentation of a preceding negative HPV test or cotest, surveillance of previous abnormal screening test results that did not require immediate colposcopic referral (e.g., follow-up after an HPV-positive cytology negative result), colposcopy/biopsy results, and follow-up surveillance tests after colposcopy or after treatment for, or resolution of, high-grade abnormalities (e.g., CIN 2+). The recognition that persistent HPV infection is necessary for developing precancer and cancer (defined as CIN 3+, which includes diagnoses of CIN 3, AIS, and cancer) underlies the 2019 guideline update. Prospective longitudinal data indicate that when a new abnormal screening test result follows a negative HPV test or cotest within the past 5 years, the estimated risk of CIN 3+ is reduced by approximately 50%.8 A negative cytology result within 3 years of a new abnormal screening test, however, does not confer a similar reduction in risk.9 The 2019 guidelines also recognize that a colposcopic examination performed according to accepted standards (e.g., using the KPNC colposcopy protocol or the ASCCP Colposcopy Standards10) confirming low-grade or normal histology reduces a patient's estimated risk of having precancer/cancer in the next 2 years.11 This allows patients with an HPV-positive ASC-US or LSIL result at their 1-year follow-up visit after a colposcopy confirming normal- or low-grade histology to return for repeat HPV or cotesting in 1 more year, rather than immediately return to colposcopy. Thus, incorporating a patient's history of previous HPV tests and colposcopy/biopsy results will permit detection and treatment of CIN 3+ while avoiding unnecessary interventions for patients with new HPV infections who are at lower risk.12

The adaptor Act1 is required for interleukin 17–dependent signaling associated with autoimmune and inflammatory disease

Abstract: T helper cells that produce interleukin 17 (IL-17) are associated with inflammation and the control of certain bacteria. We report here the essential involvement of the adaptor protein Act1 in IL-17 receptor (IL-17R) signaling and IL-17-dependent immune responses. After stimulation with IL-17, recruitment of Act1 to IL-17R required the IL-17R conserved cytoplasmic 'SEFIR' domain, followed by recruitment of the kinase TAK1 and E3 ubiquitin ligase TRAF6, which mediate 'downstream' activation of transcription factor NF-kappaB. IL-17-induced expression of inflammation-related genes was abolished in Act1-deficient primary astroglial and gut epithelial cells. This reduction was associated with much less inflammatory disease in vivo in both autoimmune encephalomyelitis and dextran sodium sulfate-induced colitis. Our data show that Act1 is essential in IL-17-dependent signaling in autoimmune and inflammatory disease.

Engaging neuroscience to advance translational research in brain barrier biology

Abstract: A great many aspects of neuronal physiology and pathology involve or affect the brain barriers. Recent insights into the role of the blood–brain barrier during development, and advances in our understanding of how it affects neurological disorders, have led to closer links between the two topics.

Genome-Wide Identification of Human RNA Editing Sites by Parallel DNA Capturing and Sequencing

Abstract: Although genetic information is stored in DNA, and faithfully copied into RNA, the cell can make the odd (and occasionally vitally important) change to the meaning of code during a process known as RNA editing. Thirteen edited genes are known in the nonrepetitive portion of the human genome, but the overall prevalence of RNA editing is unclear. Li et al. (p. [1210][1]), used an unbiased genome-wide approach to identify 239 sites (in 207 target genes), with stringent criteria for editing. The sites identified included 10 of the 13 known edited genes. Fourteen out of 18 randomly chosen sites were validated by sequencing, and these putatively edited genes were enriched for synapse, cell trafficking, and membrane functions. Furthermore, lowering the search stringency suggested that many more human genes may be edited at lower frequencies. [1]: /lookup/doi/10.1126/science.1170995