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Rahman K, Kaltenboeck B.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractDetection of anti-Chlamydia trachomatis (Ctr) antibodies is compromised by cross-reactivity and poor sensitivity of classic Ctr-antigens. We discovered 48 strongly reactive peptide antigens of Ctr-specific B-cell epitopes from 21 immunodominant proteins. In this study, we review the utility of peptide assays for diagnosis of Ctr infections. By combining many of these Ctr-specific B-cell epitopes from several proteins in separate or mixed multipeptide assays, they achieved vastly superior assay sensitivity and specificity over standard enzyme-linked immunosorbent assays. Such multipeptide assays eliminate cross-reactivities (false positives) and correct for stochastic gaps in antibody responses (false negatives). More importantly, we developed and validated a novel microarray platform in which hundreds of peptides from many proteins are spotted in a single reaction well. This offers the possibility of high-throughput screening of many candidate peptides for routine serological fingerprinting of Ctr infections. Discovery of optimal sets of antibody responses that associate with clinical pelvic inflammatory disease (PID) may identify diagnostically useful PID biomarker antigens.
Læs mere Tjek på PubMedPaavonen J, Turzanski Fortner R, Lehtinen M, et al.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractEpidemiologic, clinical, molecular and translational research findings support an interrelationship between Chlamydia trachomatis, pelvic inflammatory disease (PID), and epithelial ovarian cancer (EOC). Overall, the link between C. trachomatis, PID, and EOC seems to be relatively weak, although nondifferential misclassification bias may have attenuated the results. The predominant tubal origin of EOC and the role of chronic inflammation in tumorigenesis suggest that the association is biologically plausible. Thus, C. trachomatis and PID may represent potential risk factors or risk markers for EOC. However, many steps in this chain of events are still poorly understood and need to be addressed in future studies. Research gaps include time of exposure in relation to the long-term consequences and lag time to EOC. Data of differential risk for EOC between chlamydial and nonchlamydial PID is also needed. Another major research gap has been the absence of high-performance biomarkers for C. trachomatis, PID, and EOC, as well as EOC precursors. Biomarkers for C. trachomatis and PID leading to increased risk of EOC should be developed. If the association is confirmed, C. trachomatis and PID prevention efforts may play a role in reducing the burden of EOC.
Læs mere Tjek på PubMedDarville T.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractPelvic inflammatory disease (PID) results from ascension of sexually transmitted pathogens from the lower genital tract to the uterus and/or fallopian tubes in women, with potential spread to neighboring pelvic organs. Patients may present acutely with lower abdominal or pelvic pain and pelvic organ tenderness. Many have subtle symptoms or are asymptomatic and present later with tubal factor infertility, ectopic pregnancy, or chronic pelvic pain. Neisseria gonorrhoeae and Chlamydia trachomatis are the 2 most commonly recognized PID pathogens. Their ability to survive within host epithelial cells and neutrophils highlights a need for T-cell–mediated production of interferon γ in protection. Data indicate that for both pathogens, antibody can accelerate clearance by enhancing opsonophagocytosis and bacterial killing when interferon γ is present. A study of women with N. gonorrhoeae– and/or C. trachomatis–induced PID with histologic endometritis revealed activation of myeloid cell, cell death, and innate inflammatory pathways in conjunction with dampening of T-cell activation pathways. These findings are supported by multiple studies in mouse models of monoinfection with N. gonorrhoeae or Chlamydia spp. Both pathogens exert multiple mechanisms of immune evasion that benefit themselves and each other at the expense of the host. However, similarities in host immune mechanisms that defend against these 2 bacterial pathogens instill optimism for the prospects of a combined vaccine for prevention of PID and infections in both women and men.
Læs mere Tjek på PubMedMarrazzo J.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
Kreisel K, Llata E, Haderxhanaj L, et al.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractBackgroundPelvic inflammatory disease (PID) is an infection of the upper genital tract that has important reproductive consequences to women. We describe the burden of and trends in PID among reproductive-aged women in the United States during 2006–2016.MethodsWe used data from 2 nationally representative probability surveys collecting self-reported PID history (National Health and Nutrition Examination Survey, National Survey of Family Growth); 5 datasets containing International Classification of Diseases, Ninth/Tenth Revision codes indicating diagnosed PID (Healthcare Utilization Project; National Hospital Ambulatory Medical Care Survey, emergency department component; National Ambulatory Medical Care Survey; National Disease Therapeutic Index; MarketScan); and data from a network of sexually transmitted infection (STI) clinics (Sexually Transmitted Disease Surveillance Network). Trends during 2006–2016 were estimated overall, by age group and, if available, race/ethnicity, region, and prior STIs.ResultsAn estimated 2 million reproductive-aged women self-reported a history of PID. Three of 4 nationally representative data sources showed overall declines in a self-reported PID history, and PID emergency department and physician office visits, with small increases observed in nearly all data sources starting around 2015.ConclusionsThe burden of PID in the United States is high. Despite declines in burden over time, there is evidence of an increase in recent years.
Læs mere Tjek på PubMedXu S, Gray-Owen S.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractWhile infection by Neisseria gonorrhoeae is often asymptomatic in women, undetected infections can ascend into the upper genital tract to elicit an inflammatory response that manifests as pelvic inflammatory disease, with the outcomes depending on the intensity and duration of inflammation and whether it is localized to the endometrial, fallopian tube, ovarian, and/or other tissues. This review examines the contribution of N. gonorrhoeae versus other potential causes of pelvic inflammatory disease by considering new insights gained through molecular, immunological, and microbiome-based analyses, and the current epidemiological burden of infection, with an aim to highlighting key areas for future study.
Læs mere Tjek på PubMedKersh E, Geisler W.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractAdvancing the understanding of pelvic inflammatory disease (PID) requires access to advanced diagnostic approaches for evaluating reproductive sequelae of sexually transmitted infections (STIs). Current limitations of clinical criteria and advanced imaging technologies for diagnosing reproductive sequelae make diagnosis and surveillance of PID a challenge. We summarize and comment on major challenges in diagnostic evaluation of reproductive sequelae: limited point-of-care clinical diagnostic options for reproductive sequelae, economic and geographical obstacles to accessing state-of-the-art diagnostics, an expanding list of STIs that may cause reproductive sequelae and the complexities in evaluating them, and the need for coordinated research efforts to systematically evaluate biomarkers with gold-standard, well-defined specimens and associated clinical data. The future use of biomarkers in readily accessible mucosal or blood-derived specimens as a noninvasive approach to determining STI etiologies may be fruitful and requires more research. Biomarkers under consideration include cytokines, STI-specific antibody responses, and mRNA transcriptional profiles of inflammatory markers.
Læs mere Tjek på PubMedConnolly K, Pilligua-Lucas M, Gomez C, et al.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractMurine models of Neisseria gonorrhoeae lower reproductive tract infection are valuable systems for studying N. gonorrhoeae adaptation to the female host and immune responses to infection. These models have also accelerated preclinical testing of candidate therapeutic and prophylactic products against gonorrhea. However, because N. gonorrhoeae infection is restricted to the murine cervicovaginal region, there is a need for an in vivo system for translational work on N. gonorrhoeae pelvic inflammatory disease (PID). Here we discuss the need for well-characterized preclinical upper reproductive tract infection models for developing candidate products against N. gonorrhoeae PID, and report a refinement of the gonorrhea mouse model that supports sustained upper reproductive tract infection. To establish this new model for vaccine testing, we also tested the licensed meningococcal 4CMenB vaccine, which cross-protects against murine N. gonorrhoeae lower reproductive tract infection, for efficacy against N. gonorrhoeae in the endometrium and oviducts following transcervical or vaginal challenge.
Læs mere Tjek på PubMedMitchell C, Anyalechi G, Cohen C, et al.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractPelvic inflammatory disease (PID) is a clinical syndrome that has been associated with a wide range of potential causal pathogens. Three broad groups of organisms have been isolated from the genital tract of people with PID: sexually transmitted organisms such as Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis; bacterial vaginosis (BV)-associated species and genera such as Atopobium vaginae, Sneathia, and Megasphaera; and genera and species usually associated with the gastrointestinal or respiratory tracts such as Bacteroides, Escherichia coli, Streptococcus, or Haemophilus influenza. Although PID is often considered to be synonymous with gonorrhea or chlamydia, these pathogens are found in only one quarter to one third of people with PID, suggesting that broader screening and diagnostic and treatment strategies need to be considered to reduce the burden of PID and its associated sequelae.
Læs mere Tjek på PubMedNagarajan U, Cho C, Gyorke C, et al.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractChlamydia trachomatis-genital infection in women can be modeled in mice using Chlamydia muridarum. Using this model, it has been shown that the cytokines tumor necrosis factor (TNF)α and interleukin (IL)-1α lead to irreversible tissue damage in the oviducts. In this study, we investigated the contribution of TNFα on IL-1α synthesis in infected epithelial cells. We show that C muridarum infection enhanced TNFα-induced IL-1α expression and release in a mouse epithelial cell line. In addition to IL-1α, several TNFα-induced inflammatory genes were also highly induced, and infection enhanced TNF-induced cell death. In the mouse model of genital infection, oviducts from mice lacking the TNFα receptor displayed minimal staining for IL-1α compared with wild-type oviducts. Our results suggest TNFα and IL-1α enhance each other’s downstream effects resulting in a hyperinflammatory response to chlamydial infection. We propose that biologics targeting TNF-induced IL-1α synthesis could be used to mitigate tissue damage during chlamydial infection.
Læs mere Tjek på PubMedHorner P, Flanagan H, Horne A.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractChlamydia trachomatis (CT), the most common bacterial sexually transmitted infection worldwide, has been widely researched for its involvement in many disease pathologies in the reproductive tract, including pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility. Recent findings, through the efforts to understand the pathogenesis of CT, suggest that CT can induce the process of epithelial-to-mesenchymal transition (EMT) through epigenetic changes in the epithelium of the female reproductive tract. This literature review aims to analyze the evidence for CT’s ability to promote EMT and to pinpoint the areas that merit further investigation.
Læs mere Tjek på PubMedSoper D, Wiesenfeld H.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractMany women with lower genital tract infections associated with sexually transmitted pathogens have evidence of upper genital tract inflammation despite the absence of symptoms and signs traditionally associated with pelvic inflammatory disease (PID). New biomarkers are needed to identify these women with clinically mild PID or subclinical PID (silent salpingitis) to facilitate initiation of early treatment and ameliorate the sequelae associated with upper genital tract infection and inflammation.
Læs mere Tjek på PubMedTurpin R, Tuddenham S, He X, et al.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractBackgroundPelvic inflammatory disease (PID) leads to long-term reproductive consequences for cisgender women. Bacterial vaginosis (BV) and behavioral factors may play a role in PID pathogenesis. We assessed associations between BV, behavioral factors, and incident PID.MethodsWe analyzed participants (N = 2956) enrolled in the National Institutes of Health Longitudinal Study of Vaginal Flora, a cohort of nonpregnant cisgender women followed quarterly for 12 months. PID was defined by at least 1 of the following: cervical motion tenderness, uterine tenderness, or adnexal tenderness (160 cases). We tested associations between BV (measured using Nugent and Amsel criteria) and PID at the subsequent visit. Sociodemographic factors, sexual behaviors, and Chlamydia trachomatis (CT), untreated at baseline and concurrent with BV, were covariates in Cox proportional hazards models. Adjusting for the few Neisseria gonorrhoeae and Trichomonas vaginalis cases did not alter results.ResultsIn multivariable modeling, Nugent-BV (adjusted hazard ratio [aHR], 1.53 [95% confidence interval {CI}, 1.05–2.21]), symptomatic Amsel-BV (aHR, 2.15 [95% CI, 1.23–3.75]), and vaginal douching (aHR, 1.47 [95% CI, 1.03–2.09]) were associated with incident PID.ConclusionsBV was associated with incident PID in a large prospective cohort, controlling for behavioral factors and sexually transmitted infections (STIs). Larger studies on how BV, STIs, behaviors, and host responses interactively affect PID risk are needed.
Læs mere Tjek på PubMedTrent M, Perin J, Rowell J, et al.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractNew approaches to pelvic inflammatory disease (PID) care among adolescents and young adults (AYAs) that optimize self-care and personalize treatment are warranted to address age and racial-ethnic PID-related health disparities. Here we describe the 13-month preliminary feasibility and acceptability outcomes of recruitment, retention, and intervention delivery for Technology Enhanced Community Health Precision Nursing (TECH-PN) randomized controlled trial. Urban AYAs 13–25 years assigned female sex at birth with acute mild-moderate PID provided baseline and follow-up interview data and vaginal specimens for sexually transmitted infection (STI), cytokine, and microbiota assessment. All participants received medications and text-messaging support. Participants were block randomized to either control or intervention. Control participants received 1 community nursing visit with self-management for interim care per national guidelines. Intervention participants received unlimited precision care services driven by interim STI and macrolide resistance testing results by an advanced practice provider. In the first 13 months, 75.2% patients were eligible, and 76.1% of eligible patients enrolled. Of the participants, 94% completed the intervention and 96%, 91%, and 89%, respectively, completed their 14-, 30-, and 90-day visits. Baseline laboratory results revealed infection rates that were highest for Mycoplasma genitalium (45%) followed by Chlamydia trachomatis (31%). Preliminary enrollment, STI, intervention delivery, and retention data demonstrate the feasibility and acceptability of the TECH-PN intervention and support rationale for precision care for PID among urban AYAs.ClinicalTrials.gov Identifier. NCT03828994.
Læs mere Tjek på PubMedHorner P, Anyalechi G, Geisler W.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractChlamydiatrachomatis (CT) causes pelvic inflammatory disease, which may result in tubal factor infertility (TFI) in women. Serologic assays may be used to determine the proportion of women with and without TFI who have had previous CT infection and to generate estimates of infertility attributable to chlamydia. Unfortunately, most existing CT serologic assays are challenged by low sensitivity and, sometimes, specificity for prior CT infection; however, they are currently the only available tests available to detect prior CT infection. Modeling methods such as finite mixture modeling may be a useful adjunct to quantitative serologic data to obtain better estimates of CT-related infertility. In this article, we review CT serological assays, including the use of antigens preferentially expressed during upper genital tract infection, and suggest future research directions. These methodologic improvements, coupled with creation of new biomarkers for previous CT infection, should improve our understanding of chlamydia’s contribution to female infertility.
Læs mere Tjek på PubMedZheng X, Zhong W, O’Connell C, et al.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractBackgroundChlamydia trachomatis (Ct) infection ascending to the upper genital tract can cause infertility. Direct association of genetic variants as contributors is challenging because infertility may not be diagnosed until years after infection. Investigating the intermediate trait of ascension bridges this gap.MethodsWe identified infertility genome-wide association study (GWAS) loci using deoxyribonucleic acid from Ct-seropositive cisgender women in a tubal factor infertility study and Ct-infected cisgender women from a longitudinal pelvic inflammatory disease cohort with known fertility status. Deoxyribonucleic acid and blood messenger ribonucleic acid from 2 additional female cohorts with active Ct infection and known endometrial infection status were used to investigate the impact of infertility single-nucleotide polymorphisms (SNPs) on Ct ascension. A statistical mediation test examined whether multiple infertility SNPs jointly influenced ascension risk by modulating expression of mediator genes.ResultsWe identified 112 candidate infertility GWAS loci, and 31 associated with Ct ascension. The SNPs altered chlamydial ascension by modulating expression of 40 mediator genes. Mediator genes identified are involved in innate immune responses including type I interferon production, T-cell function, fibrosis, female reproductive tract health, and protein synthesis and degradation.ConclusionsWe identified Ct-related infertility loci and their potential functional effects on Ct ascension.
Læs mere Tjek på PubMedRussell M.
Journal of Infectious Diseases, 16.08.2021
Tilføjet 16.08.2021
AbstractPelvic inflammatory disease and infertility frequently develop after female genital tract infection with Neisseria gonorrhoeae, but determining their etiology from among various possibilities presents difficulties. Exploitation of serology to identify the causative agent is complicated by numerous factors, and no immunological test currently exists to determine unequivocally whether an individual currently is, or has been, infected with N. gonorrhoeae. The extensive antigenic variability of N. gonorrhoeae and its expression of antigens shared with other Neisseria species commonly carried in humans render problematic an assay that is specific for all gonococcal strains. However, novel conserved gonococcal antigens identified for potential vaccines may find additional application in diagnostic assays. N. gonorrhoeae also interferes with the adaptive immune response, and antibody responses to uncomplicated infection are usually weak. Elucidating the mechanisms whereby N. gonorrhoeae manipulates the human immune system may lead to improved understanding of the pathogenesis of pelvic inflammatory disease and infertility.
Læs mere Tjek på PubMedBhalala, Utpal S.; Gist, Katja M.; Tripathi, Sandeep; Boman, Karen; Kumar, Vishakha K.; Retford, Lynn; Chiotos, Kathleen; Blatz, Allison M.; Dapul, Heda; Verma, Sourabh; Sayed, Imran A.; Gharpure, Varsha P.; Bjornstad, Erica; Tofil, Nancy; Irby, Katherine; Sanders, Ronald C. Jr; Heneghan, Julia A.; Thomas, Melissa; Gupta, Manoj K.; Oulds, Franscene E.; Arteaga, Grace M.; Levy, Emily R.; Gupta, Neha; Kaufman, Margit; Abdelaty, Amr; Shlomovich, Mark; Medar, Shivanand S.; Iqbal O’Meara, A. M.; Kuehne, Joshua; Menon, Shina; Khandhar, Paras B.; Miller, Aaron S.; Barry, Suzanne M.; Danesh, Valerie C.; Khanna, Ashish K.; Zammit, Kimberly; Stulce, Casey; McGonagill, Patrick W.; Bercow, Asher; Amzuta, Ioana G.; Gupta, Sandeep; Almazyad, Mohammed A.; Pierre, Louisdon; Sendi, Prithvi; Ishaque, Sidra; Anderson, Harry L. III; Nawathe, Pooja; Akhter, Murtaza; Lyons, Patrick G.; Chen, Catherine; Walkey, Allan J.; Bihorac, Azra; Wada Bello, Imam; Ben Ari, Judith; Kovacevic, Tanja; Bansal, Vikas; Brinton, John T.; Zimmerman, Jerry J.; Kashyap, Rahul; For The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Gr
Critical Care Medicine, 14.08.2021
Tilføjet 16.08.2021
Objectives:
Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry.
Design:
Retrospective study.
Setting:
Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry.
Patients:
Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021.
Interventions:
None.
Measurements and Main Results:
The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25–14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16–25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2–7.7 d) and 4 days (1.9–7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased.
Conclusions:
In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.
New affiliations for Dr. Bhalala: The Children’s Hospital of San Antonio, Baylor College of Medicine, San Antonio, TX; and. Driscoll Children’s Hospital, Corpus Christi, TX. This work was performed at Multiple participating institutions (mentioned above); Society of Critical Care Medicine headquarters, Mount Prospect, IL, was Data Coordinating Center.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).
All of the authors listed on this article had substantial contribution to the conception or design of the work or the acquisition, analysis, or interpretation of data for the article and drafting of the work or revising it critically for important intellectual content. The final article was approved, and all members were in agreement and accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Supported, in part, by the Gordon and Betty Moore Foundation and Janssen Research & Development, LLC. Supported, in part, also by the National Institutes of Health/National Center for Research Resources/National Center for Clinical and Translational Science, Center for Translational Science Activity Grant Number UL1 TR002377.
Dr. Bhalala is currently funded by the National Institutes of Health (NIH) (Site Principal Investigator [PI] for Stress Hydrocortisone in Pediatric Septic Shock—R01HD096901), The Children’s Hospital of Philadelphia (Site-PI for Pediatric Resuscitation Quality Collaborative – PediResQ), Voelcker Pilot Grant (PI for project on prearrest electrocardiographic changes), The Children’s Hospital of San Antonio Endowed Chair Funds for ancillary projects related to Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) (coronavirus disease 2019 [COVID-19]) Registry and SCCM VIRUS electronic medical records, automation pilot. Ms. Boman’s institution received funding from The Gordon and Betty Moore Foundation. His institution received funding from Janssen Research and Development LLC. Dr. Kumar currently funded by Gordon and Betty Moore Foundation, Centers for Disease Control and Prevention (CDC) Foundation through University of Washington and Janssen Research & Development, LLC. Dr. Chiotos funded by Agency for Healthcare Research and Quality(K12-HS026393). Dr. Bjornstad’s institution received funding from the International Society of Nephrology, The NIH-National Institute of Diabetes and Digestive and Kidney Diseases/T32, and Bioporto. Dr. Dapul disclosed that the deidentified data of some patients submitted to the VIRUS registry were also used in the Overcoming COVID-19 Virus Registry. Dr. Blatz funded by NIH grant T32GM-075766. Dr. Levy’s institution received funding from the CDC (No. 75D30120C07725) and the National Institute of Allergy and Infectious Diseases (AI 144301); she received funding from SinoUnited Health Shanghai Children’s Hospital. Drs. Kaufman’s, Abdelaty’s, and Briton’s institutions received funding from SCCM. Dr. Kaufman received funding from EngleWood Health for consulting work as medical director. Dr. Khanna’s institution received funding for COVID-19 trials Blood Volume Analyzer-Daxor and Chair Steering Committee for the Siltuximab in Selected Hospitalized Patients With Viral Acute Respiratory Distress Syndrome trial. Dr. Khanna is currently funded by a Clinical Translational Science Institute NIH/National Center for Advanced Translational Science KL2 TR001421 award for a trial on continuous postoperative hemodynamic and saturation monitoring and is a site PI (institutional funding) for a randomized trial of cytokine filtration in severe COVID-19 and a prospective observational trial of blood volume assessment in COVID-19. His institution also received funding for the SCCM VIRUS EMR automation pilot. Dr. Stulce received funding from the American Physician Institute. Dr. Anderson III disclosed that he is on the Advisory Board for the Gift of Life Michigan. Dr. Bello disclosed government work. Dr. Walkey currently funded the NIH/National Heart, Lung and Blood Institute (NHLBI) grants R01HL151607, R01HL139751, R01HL136660, Agency of Healthcare Research and Quality, R01HS026485, Boston Biomedical Innovation Center/NIH/NHLBI 5U54HL119145-07, and royalties from UptoDate. Dr. Bihorac received support for article research from the NIH. His institution received funding from the NIH (R01 GM110240 R21 EB 027344), Atox Bio, Astute Medical Research, Mallinckrodt Pharmaceuticals, and La Jolla Pharmaceuticals; she disclosed three institutional patents (20200161000, WO2020172607A12020, and 20190326013). Dr. Zimmerman’s institution received funding from the NIH-National Institute of Child Health and Human Development and Immunexpress; he received funding from Elsevier Publishing. Dr. Kashyap receives funding from the NIH/NHLBI: R01HL 130881, UG3/UH3HL 141722; Gordon and Betty Moore Foundation, and Janssen Research & Development, LLC; and royalties from Ambient Clinical Analytics. The remaining authors have disclosed that they do not have any potential conflicts of interest.
Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.
Members of the initiative are listed in the Appendix (http://links.lww.com/CCM/G617).
ClinicalTrials.gov Identifier: NCT04323787.
For information regarding this article, E-mail: utpal.bhalala@bcm.edu
Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedSemple, Diarmaid; Howlett, Moninne M.; Strawbridge, Judith D.; Breatnach, Cormac V.; Hayden, John C.
Critical Care Medicine, 14.08.2021
Tilføjet 16.08.2021
Objectives:
Pediatric delirium is a neuropsychiatric disorder with disrupted cerebral functioning due to underlying disease and/or critical care treatment. Pediatric delirium can be classified as hypoactive, hyperactive, and mixed. This systematic review was conducted to estimate the pooled prevalence of pediatric delirium using validated assessment tools in children (Cornell Assessment of Pediatric Delirium, Pediatric Confusion Assessment Method for the ICU, PreSchool Confusion Assessment Method for the ICU, Pediatric Confusion Assessment Method for the ICU Severity Scale, and Sophia Observation Withdrawal Symptoms Pediatric Delirium scale), identify modifiable and nonmodifiable risk factors, and explore the association of pediatric delirium with clinical outcomes.
Data Sources:
A systematic search of PubMed, EMBASE, and CINAHL databases was undertaken for full articles pertaining to pediatric delirium prevalence.
Study Selection:
No language or date barriers were set. Studies were included where the following eligibility criteria were met: study design aimed to estimate pediatric delirium prevalence arising from treatment in the intensive care setting, using a validated tool. Only randomized controlled trials, cross-sectional studies, or cohort studies allowing an estimate of the prevalence of pediatric delirium were included.
Data Extraction:
Data were extracted by the primary researcher (D.S.) and accuracy checked by coauthors.
Data Synthesis:
A narrative synthesis and pooled prevalence meta-analysis were undertaken.
Conclusions:
Pediatric delirium, as determined by the Cornell Assessment of Pediatric Delirium score, is estimated to occur in 34% of critical care admissions. Eight of 11 studies reporting on subtype identified hypoactive delirium as most prevalent (46–81%) with each of the three remaining reporting either hyperactive (44%), mixed (57%), or equal percentages of hypoactive and mixed delirium (43%) as most prevalent. The development of pediatric delirium is associated with cumulative doses of benzodiazepines, opioids, the number of sedative classes used, deep sedation, and cardiothoracic surgery. Increased time mechanically ventilated, length of stay, mortality, healthcare costs, and associations with decreased quality of life after discharge were also found. Multi-institutional and longitudinal studies are required to better determine the natural history, true prevalence, long-term outcomes, management strategies, and financial implications of pediatric delirium.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).
D. Semple received funding from The Royal College of Surgeons in Ireland School of Pharmacy and Biomolecular Sciences. D. Semple and Dr. Howlett disclosed the off-label product use of medicines not licensed for use in children. The remaining authors have disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: diarmaidsemple@rcsi.ie
Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedWang, Wen; Zhu, Shichao; He, Qiao; Wang, Mingqi; Kang, Yan; Zhang, Rui; Ji, Peng; Zou, Kang; Klompas, Michael; Zong, Zhiyong; Sun, Xin
Critical Care Medicine, 14.08.2021
Tilføjet 16.08.2021
Objectives:
Fluid therapy is an important component of intensive care management, however, optimal fluid management is unknown. The relationship between fluid balance and ventilator-associated events has not been well established. This study investigated the dose-response relationship between fluid balance and ventilator-associated events.
Design:
Nested case-control study.
Setting:
The study was based on a well-established, research-oriented registry of healthcare-associated infections at ICUs of West China Hospital system (Chengdu, China).
Patients:
A total of 1,528 ventilator-associated event cases with 3,038 matched controls, who consistently underwent mechanical ventilation for at least 4 days from April 1, 2015, to December 31, 2018, were included.
Interventions:
None.
Measurements and Main Results:
We calculated cumulative fluid balance within 4 days prior to ventilator-associated event occurrence. A weighted Cox proportional hazards model with restricted cubic splines was used to evaluate the dose-response relationship. A nonlinear relationship between fluid balance and all three tiers of ventilator-associated events, patients with fluid balance between –1 and 0 L had the lowest risk (p < 0.05 for nonlinear test). The risk of ventilator-associated event was significantly higher in patients with positive fluid balance (4 d cumulative fluid balance: 1 L: 1.19; 3 L: 1.92; 5 L: 2.58; 7 L: 3.24), but not in those with negative fluid balance (–5 L: 1.34; –3 L: 1.14; –1 L: 0.98).
Conclusions:
There was nonlinear relationship between fluid balance and all three tiers of ventilator-associated event, with an fluid balance between –1 and 0 L corresponding to the lowest risk. Positive but not negative fluid balance increased the risk of ventilator-associated events, with higher positive fluid balance more likely to lead to ventilator-associated events.
This work was performed at Chinese Evidence-based Medicine Center and CREAT Group, West China Hospital, Sichuan University, Chengdu, 610041, China.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).
Drs. Zong and Sun contributed equally and shared corresponding authorship.
Dr. Wang received support from National Key Research and Development Program (Grant No. 2020YFC2009003). Dr. Sun received support for article research from the Sichuan Youth Science and Technology Innovation Research Team (Grant No. 2020JDTD0015), and the 1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (Grant No. ZYYC08003). Dr. Zong received support from the 1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (Grant No. ZYYC08006). Drs. Zou and Zong received support for article research from the National Natural Science Foundation of China. Dr. Klompas’ institution received funding from the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, and the Massachusetts Department of Public Health; he received funding from UpToDate. The remaining authors have disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: sunxin@wchscu.cnzongzhiyong@gmail.com
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedHossain, Saamia; Pastores, Stephen M.
Critical Care Medicine, 14.08.2021
Tilføjet 16.08.2021
Takayama, Wataru; Endo, Akira; Morishita, Koji; Otomo, Yasuhiro
Critical Care Medicine, 14.08.2021
Tilføjet 16.08.2021
Objectives:
To evaluate the utility of dielectric blood coagulometry for early sepsis–induced disseminated intravascular coagulation diagnosis.
Design:
Single-center, prospective observational study.
Setting:
Patients with sepsis or septic shock at the Tokyo Medical and Dental University Hospital of Medicine between September 2019 and September 2020.
Patients:
The patients were divided into three groups according to the timing of disseminated intravascular coagulation diagnosis based on the Disseminated Intravascular Coagulation score by the Japanese Association for Acute Medicine: 1) no disseminated intravascular coagulation group, 2) late-diagnosed disseminated intravascular coagulation group: not diagnosed with disseminated intravascular coagulation on day 1 but diagnosed within 48 hours after admission, and 3) disseminated intravascular coagulation group: diagnosed with disseminated intravascular coagulation on day 1. The study evaluated 80 patients (no disseminated intravascular coagulation, 31 [38.8%]; late-diagnosed disseminated intravascular coagulation, 34 (42.5%); disseminated intravascular coagulation, 15 [18.8%]).
Measurements and Main Results:
We compared the clinical severity scores and mortality of the groups and assessed the correlation between the dielectric blood coagulometry–derived coagulation marker, thrombin levels, and Disseminated Intravascular Coagulation score using Spearman rank correlation. The mortality rate was 0% (0/31) in the no disseminated intravascular coagulation group, 35.3% (12/34) in the late-diagnosed disseminated intravascular coagulation group, and 33.3% (5/15) in the disseminated intravascular coagulation group. Although the Disseminated Intravascular Coagulation score on day 1 did not reflect disseminated intravascular coagulation in approximately 70% of patients who developed disseminated intravascular coagulation by day 2, dielectric clot strength measured by dielectric blood coagulometry on day 1 strongly correlated with disseminated intravascular coagulation development by day 2 (Spearman ρ = 0.824; p < 0.05) and with thrombin level on day 1 (Spearman ρ = 0.844; p < 0.05).
Conclusions:
Dielectric blood coagulometry can be used to detect early-phase disseminated intravascular coagulation in patients with sepsis and is strongly correlated with thrombin levels. Larger studies are needed to verify our results for developing clinical applications.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).
Dr. Takayama received funding from the Japan Society for the Promotion of Science KAKENHI grant number T20K17854-0. The remaining authors have disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: tak2accm@tmd.ac.jp
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedLazzeri, Chiara; Bonizzoli, Manuela; Peris, Adriano
Critical Care Medicine, 14.08.2021
Tilføjet 16.08.2021
Daniel T. Marggrander, Sinem Koç-Günel, Nesrin Tekeli-Camcı, Simon Martin, Rejane Golbach, Timo Wolf
International Journal of Infectious Diseases, 15.08.2021
Tilføjet 15.08.2021
The lung is the organ most commonly affected by complications in people living with HIV (PLWH) (Benito et al, 2012). The most common AIDS-defining disease is Pneumocystis jirovecii pneumonia (PCP), which is the second most frequent infectious lung disease in HIV-patients (Benito et al, 2012). Several other infectious and malignant diseases also commonly affect the lung in AIDS (Benito et al, 2012, Unnwehr et al, 2020). Furthermore, PLWH have an increased risk of developing bacterial pneumonia, which is the most frequent pulmonary complication and cause of hospitalisation in HIV-patients of all ages, independent of disease stage (Benito et al, 2012 Gray and Zar, 2010, Maddedu et al, 2010).
Læs mere Tjek på PubMedMaarten M. Immink, Eric R.A. Vos, Alcira V.A. Janga-Jansen, Sharda Baboe-Kalpoe, Koen Hulshof, Jeffrey van Vliet, Jeroen Kerkhof, Gerco den Hartog, Hester E. de Melker, Fiona R.M. van der Klis, Nicoline A.T. van der Maas
International Journal of Infectious Diseases, 15.08.2021
Tilføjet 15.08.2021
Pertussis or whooping cough is a highly contagious respiratory disease caused mainly by the bacterium Bordetella pertussis. Infants too young to be vaccinated are the most vulnerable to severe complications, e.g., pneumonia, which often leads to hospitalization and sometimes death (van der Maas et al., 2016, Vegelin et al., 1998). Such infants depend on placentally-transferred maternal antibodies for protection against disease (Amirthalingam et al., 2014, Winter et al., 2017). In older children and adults, pertussis often manifests mildly and symptoms remain unrecognized, whereas adults with comorbidities and elderly are at higher risk of severe pertussis complications and hospitalization (Edwards and Freeman, 2006, Kandeil et al., 2019, Rothstein and Edwards, 2005).
Læs mere Tjek på PubMedKazuo Imai, Masaru Matsuoka, Sakiko Tabata, Yutaro Kitagawa, Mayu Nagura-Ikeda, Katsumi Kubota, Ai Fukada, Tomohito Takada, Momoko Sato, Sakiko Noguchi, Shinichi Takeuchi, Noriaki Arakawa, Kazuyasu Miyoshi, Yoshiro Saito, Takuya Maeda
International Journal of Infectious Diseases, 14.08.2021
Tilføjet 15.08.2021
Novel coronavirus disease 2019 (COVID-19), which is caused by the lineage B betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic worldwide . An understanding of the humoral immune response against SARS-CoV-2 is important for assessing the potential for viral re-infection, diagnosis, surveillance, and pathogenesis. SARS-CoV-2 contains four major structural proteins, including the spike (S), membrane (M), and envelope (E) proteins that form the viral envelope, and the nucleocapsid (N) protein, which is located in the ribonucleoprotein core.
Læs mere Tjek på PubMedChristian Selinger, Marc Choisy, Samuel Alizon
International Journal of Infectious Diseases, 14.08.2021
Tilføjet 14.08.2021
The COVID-19 pandemic revealed the importance of identifying early predictors of epidemic dynamics. Indeed, for this infectious disease, hospital admission data is usually the most reliable indicator but it suffers from a two weeks delay with the current state of the epidemic (Salje et al., 2020; Sofonea et al., 2021). Screening test results can provide closer monitoring but they often suffer from strong sampling biases.
Læs mere Tjek på PubMedMonica Birkhead, Allison J Glass, Heather Allan-Gould, Carice Goossens, Colleen A Wright
International Journal of Infectious Diseases, 14.08.2021
Tilføjet 14.08.2021
Since the initial Lancet correspondence by Goldsmith et al. (2020), there have been numerous published electron micrographs of putative SARS-CoV-2 virions in biopsy and autopsy tissues. A recent review of these images (Bullock et al., 2021) indicated that previous ultrastructural reports of virions in placental tissue, were mis-identifications. Placental histology of mothers and neonates both testing positive for SARS-CoV-2, is typified by chronic histiocytic intervillositis and trophoblast necrosis, with RNA in situ hybridization/immuno-histochemical findings localising viral RNA/viral antigens to the syncytiotrophoblast (Schwartz and Morotti, 2020).
Læs mere Tjek på PubMedJenny Wright, Felix Achana, Lavanya Diwakar, Malcolm G Semple, Will D Carroll, Kenneth Baillie, Christopher Thompson, Alice Alcock, Timothy S Kemp
International Journal of Infectious Diseases, 14.08.2021
Tilføjet 14.08.2021
Clinicians need to identify patients with a higher risk of poor outcome and mortality from Covid-19 at an early stage of hospital admission. We describe a prospective, observational cohort study conducted at a UK tertiary care hospital to determine the relationship between the likelihood of death and Ct values in an unvaccinated UK population with Covid-19 on admission to hospital. Statistical adjustment was made for other known risk factors associated with poor outcome. Cycle thresholds (Ct) are semi-quantitative values, which are inversely proportional to the viral load in a revere transcription polymerase chain reaction (PCR) test for SARS-CoV-2.
Læs mere Tjek på PubMedMalaria Journal, 1.12.2021
Tilføjet 14.08.2021
Abstract
Individual thermal comfort models based on physiological parameters could improve the efficiency of the personal thermal comfort control system. However, the effect of thermal history has not been fully addressed in these models. In this study, climate chamber experiments were conducted in winter using 32 subjects who have different indoor and outdoor thermal histories. Two kinds of thermal conditions were investigated: the temperature dropping (24–16 °C) and severe cold (12 °C) conditions. A simplified method using historical air temperature to quantify the thermal history was proposed and used to predict thermal comfort and thermal demand from physical or physiological parameters. Results show the accuracies of individual thermal sensation prediction was low to about 30% by using the PMV index in cold environments of this study. Base on the sensitivity and reliability of physiological responses, five local skin temperatures (at hand, calf, head, arm and thigh) and the heart rate are optimal input parameters for the individual thermal comfort model. With the proposed historical air temperature as an additional input, the general accuracies using classification tree model C5.0 were increased up by 15.5% for thermal comfort prediction and up by 29.8% for thermal demand prediction. Thus, when predicting thermal demands in winter, the factor of thermal history should be considered.
Læs mere Tjek på PubMedMalaria Journal, 1.12.2021
Tilføjet 14.08.2021
Abstract
In case of lightly loaded radial ball bearings, failure mechanisms other than fatigue such as smearing of raceways due to increased frictional torque and vibrations often prevail. Hence, attempts have been made herein for reducing the frictional torque and minimizing the vibrations of a radial deep groove ball bearing employing surface textures at the inner race. Nanosecond pulsed laser was used to create texture (involving micro-dimples having different dimple area density) on the inner race of test bearings. Using an in-house developed test rig, frictional torque and vibrational parameters were measured at different speeds and light loads (i.e. in vicinity of 0.01C, where C is dynamic load capacity of radial ball bearing). Significant reduction in frictional torque and overall vibrations were found in the presence of micro-dimples on inner race at light loads irrespective of operating speeds. Even without satisfying the minimum load needed criteria for the satisfactory operation, substantial reduction in smearing marks was found on the races of textured ball bearings in comparison to conventional cases.
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