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Article ; Online: C

Mart, Matthew F / Semler, Matthew W / Bernard, Gordon / Casey, Jonathan D / Ely, E Wesley / Freundlich, Robert / Jackson, James C / Kiehl, Amy / Jenkins, Cathy / Wang, Guanchao / Lindsell, Christopher / Bryant, Patsy / Rice, Todd W / Self, Wesley H / Stollings, Joanna / Wanderer, Jonathan P / Wang, Li / Han, Jin Ho

BMJ open

2022 Volume 12, Issue 11, Page(s) e064517

Abstract: Introduction: Long-term cognitive impairment is one of the most common complications of critical illness among survivors who receive mechanical ventilation. Recommended oxygen targets during mechanical ventilation vary among international guidelines. ... ...

Abstract	Introduction: Long-term cognitive impairment is one of the most common complications of critical illness among survivors who receive mechanical ventilation. Recommended oxygen targets during mechanical ventilation vary among international guidelines. Different oxygen targets during mechanical ventilation have the potential to alter long-term cognitive function due to cerebral hypoxemia or hyperoxemia. Whether higher, intermediate or lower SpO Methods and analysis: The Ethics and dissemination: The CO-PILOT ancillary study was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.
MeSH term(s)	Humans ; Critical Illness ; Quality of Life ; Pilots ; Oxygen ; Cognition ; Randomized Controlled Trials as Topic
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2022-11-01
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-064517
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Article ; Online: Myeloid C-type lectin receptors in innate immune recognition.

Reis E Sousa, Caetano / Yamasaki, Sho / Brown, Gordon D

Immunity

2024 Volume 57, Issue 4, Page(s) 700–717

Abstract: C-type lectin receptors (CLRs) expressed by myeloid cells constitute a versatile family ...

Abstract	C-type lectin receptors (CLRs) expressed by myeloid cells constitute a versatile family of receptors that play a key role in innate immune recognition. Myeloid CLRs exhibit a remarkable ability to recognize an extensive array of ligands, from carbohydrates and beyond, and encompass pattern-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and markers of altered self. These receptors, classified into distinct subgroups, play pivotal roles in immune recognition and modulation of immune responses. Their intricate signaling pathways orchestrate a spectrum of cellular responses, influencing processes such as phagocytosis, cytokine production, and antigen presentation. Beyond their contributions to host defense in viral, bacterial, fungal, and parasitic infections, myeloid CLRs have been implicated in non-infectious diseases such as cancer, allergies, and autoimmunity. A nuanced understanding of myeloid CLR interactions with endogenous and microbial triggers is starting to uncover the context-dependent nature of their roles in innate immunity, with implications for therapeutic intervention.
MeSH term(s)	Humans ; Lectins, C-Type/metabolism ; Immunity, Innate ; Myeloid Cells/metabolism ; Signal Transduction ; Neoplasms/metabolism ; Receptors, Pattern Recognition/metabolism
Chemical Substances	Lectins, C-Type ; Receptors, Pattern Recognition
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2024.03.005
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 69: Show issues

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Article ; Online: Increasing Treatment Rates for Hepatitis C in Primary Care.

Stewart, Ann / Craig-Neil, Amy / Hodwitz, Kathryn / Wang, Rick / Cheng, Doret / Arbess, Gordon / Jeon, Caroline / Juando-Prats, Clara / Kiran, Tara

Journal of the American Board of Family Medicine : JABFM

2023 Volume 36, Issue 4, Page(s) 591–602

Abstract: Background: Despite antiviral agents that can cure the disease, many individuals with Hepatitis C ...

Abstract	Background: Despite antiviral agents that can cure the disease, many individuals with Hepatitis C Virus (HCV) remain untreated. Primary care clinicians can play an important role in HCV treatment but often feel they do not have the requisite skills. Methods: We implemented a population-based improvement intervention over 10 months to support treatment of HCV in a primary care setting. The intervention included a decision-support tool, education for clinicians, enhanced interprofessional team supports, mentorship, and proactive patient outreach. We used process and outcome measures to understand the impact on the proportion of patients who initiated treatment and achieved Sustained Virologic Response (SVR). We used physician focus groups and pharmacist interviews to understand the context and mechanisms influencing the impact of the intervention. Results: Between December 2018 and June 2020, the percentage of HCV RNA positive patients who started treatment rose from 66.0% (354/536) to 75.5% (401/531) with 92.5% (371/401) of those starting treatment achieving SVR. Qualitative findings highlighted that the intervention helped raise awareness and confidence among physicians for treating HCV in primary care. A collaborative team environment, education, mentorship, and a decision-support tool integrated into the electronic record were all enablers of success although patient psychosocial complexity remained a barrier to engagement in treatment. Conclusion: A multifaceted primary care improvement initiative increased clinician confidence and was associated with an increase in the proportion of HCV RNA positive patients who initiated curative treatment.
MeSH term(s)	Humans ; Hepacivirus ; Hepatitis C/drug therapy ; Antiviral Agents/therapeutic use ; Primary Health Care ; RNA/therapeutic use ; Hepatitis C, Chronic/drug therapy ; Treatment Outcome
Chemical Substances	Antiviral Agents ; RNA (63231-63-0)
Language	English
Publishing date	2023-07-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2239939-2
ISSN	1558-7118 ; 1557-2625
ISSN (online)	1558-7118
ISSN	1557-2625
DOI	10.3122/jabfm.2022.220427R1
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Zs.A 2626: Show issues

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Article ; Online: Association of Three Novel Inflammatory Markers: Lymphocyte to HDL-C Ratio, High-Sensitivity C-Reactive Protein to HDL-C Ratio and High-Sensitivity C-Reactive Protein to Lymphocyte Ratio With Metabolic Syndrome.

Kolahi Ahari, Rana / Akbari, Nazanin / Babaeepoor, Negin / Fallahi, Zahra / Saffar Soflaei, Sara / Ferns, Gordon / Ebrahimi, Mahmoud / Moohebati, Mohsen / Esmaily, Habibollah / Ghayour-Mobarhan, Majid

Endocrinology, diabetes & metabolism

2024 Volume 7, Issue 3, Page(s) e00479

Abstract: ... cholesterol (HDL-C) ratio (LHR), high-sensitivity C-reactive protein (hs-CRP) to HDL-C ratio (HCHR) and hs-CRP ...

Abstract	Objective: We aimed to compare the association of three novel inflammatory indicators with metabolic syndrome (MetS) among Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort participants. Methods: According to the International Diabetes Federation (IDF) criteria, the cohort participants were divided into the MetS(+) and MetS(-) groups. The lymphocyte to high-density lipoprotein cholesterol (HDL-C) ratio (LHR), high-sensitivity C-reactive protein (hs-CRP) to HDL-C ratio (HCHR) and hs-CRP to lymphocyte ratio (HCLR) were calculated and were compared between the groups. Binary logistic regression (LR) analysis was performed to find the association of the indices with the presence of MetS among men and women. Receiver-operating characteristic (ROC) curve analysis was used to establish cut-off values in predicting MetS for men and women. p-Values <0.05 were considered as statistically significant. Results: Among a total of 8890 participants (5500 MetS(-) and 3390 MetS(+)), LHR, HCHR and HCLR were significantly higher in the MetS(+) group than in MetS(-) group (p < 0.001). In LR analysis, after adjusting for multiple cofounders, LHR remained an independent factor for the presence of MetS among men (OR: 1.254; 95% CI: 1.202-1.308; p < 0.001) and women (OR: 1.393; 95% CI: 1.340-1.448; p < 0.001). HCHR also remained an independent factor for the presence of MetS only in women (OR: 1.058; 95% CI: 1.043-1.073; p < 0.001). ROC curve analysis showed that LHR had the higher AUC for predicting MetS in both men (AUC: 0.627; 95% CI: 0.611-0.643; p < 0.001) and women (AUC: 0.683; 95% CI: 0.670, 0.696; p < 0.001). Conclusion: This suggests that among both genders, the LHR as an inexpensive and easy-to-access marker has a better diagnostic performance and could be a promising alternative to the traditional expensive inflammatory markers such as hs-CRP for the evaluation of inflammation in patients with MetS.
MeSH term(s)	Humans ; Male ; Female ; Metabolic Syndrome/diagnosis ; Metabolic Syndrome/etiology ; Metabolic Syndrome/metabolism ; C-Reactive Protein/metabolism ; Cholesterol, HDL ; Diabetes Mellitus ; Lymphocytes/metabolism
Chemical Substances	C-Reactive Protein (9007-41-4) ; Cholesterol, HDL
Language	English
Publishing date	2024-04-08
Publishing country	England
Document type	Journal Article
ISSN	2398-9238
ISSN (online)	2398-9238
DOI	10.1002/edm2.479
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Article ; Online: Characteristics associated with receipt of treatment among patients diagnosed with chronic hepatitis C virus.

Gordon, Stuart C / Kaushik, Ankita / Chastek, Benjamin / Anderson, Amy / Yehoshua, Alon

Journal of viral hepatitis

2023 Volume 30, Issue 9, Page(s) 756–764

Abstract: Although current guidelines recommend that nearly all patients with chronic hepatitis C virus (HCV ...

Abstract	Although current guidelines recommend that nearly all patients with chronic hepatitis C virus (HCV) infection receive treatment, a substantial proportion remain untreated. We conducted an administrative claims analysis to provide real-world data on treatment patterns and characteristics of treated versus untreated patients among individuals with HCV in the United States. Adults with an HCV diagnosis from 01 July 2016 through 30 September 2020 and continuous health plan enrolment for 12 months before and ≥1 month after the diagnosis date were identified in the Optum Research Database. Descriptive and multivariable analyses were conducted to evaluate the association between patient characteristics and the rate of treatment. Of 24,374 patients identified with HCV, only 30% initiated treatment during follow-up. Factors associated with increased rate of treatment included younger age versus age 75+ (hazard ratio [HR] 1.50-1.83 depending on age group), commercial versus Medicare insurance (HR 1.32), and diagnosis by a specialist versus a primary care physician (HR 2.56 and 2.62 for gastroenterology and infectious disease or hepatology, respectively) (p < .01 for all). Several baseline comorbidities were associated with decreased rate of treatment, including psychiatric disorders (HR 0.87), drug use disorders (HR 0.85) and cirrhosis (HR 0.42) (p < .01 for all). These findings highlight existing HCV treatment inequities, particularly among older patients and those with psychiatric disorders, substance use disorders or chronic comorbidities. Targeted efforts to increase treatment uptake in these populations could mitigate a considerable future burden of HCV-related morbidity, mortality and healthcare costs.
MeSH term(s)	Adult ; Humans ; Aged ; United States/epidemiology ; Hepatitis C, Chronic/diagnosis ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/epidemiology ; Antiviral Agents/therapeutic use ; Medicare ; Health Care Costs ; Comorbidity ; Retrospective Studies ; Hepatitis C/epidemiology
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2023-06-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1212497-7
ISSN	1365-2893 ; 1352-0504
ISSN (online)	1365-2893
ISSN	1352-0504
DOI	10.1111/jvh.13860
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Zs.A 4119: Show issues

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Article ; Online: Correction to: Real-World Safety and Effectiveness of an 8-Week Regimen of Glecaprevir/Pibrentasvir in Patients with Hepatitis C and Cirrhosis.

Lu, Mei / Rupp, Loralee B / Melkonian, Christina / Trudeau, Sheri / Daida, Yihe G / Schmidt, Mark A / Gordon, Stuart C

Advances in therapy

2024

Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Published Erratum
ZDB-ID	632651-1
ISSN	1865-8652 ; 0741-238X
ISSN (online)	1865-8652
ISSN	0741-238X
DOI	10.1007/s12325-024-02858-1
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Zs.A 2101: Show issues

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Article ; Online: Dynamic risk assessment for hepatocellular carcinoma in patients with chronic hepatitis C.

Lu, Mei / Salgia, Reena / Li, Jia / Trudeau, Sheri / Rupp, Loralee B / Wu, Trueman / Daida, Yihe G / Schmidt, Mark A / Gordon, Stuart C

Journal of viral hepatitis

2023 Volume 30, Issue 9, Page(s) 746–755

Abstract: Chronic hepatitis C (HCV) is a primary cause of hepatocellular carcinoma (HCC). Although antiviral ...

Abstract	Chronic hepatitis C (HCV) is a primary cause of hepatocellular carcinoma (HCC). Although antiviral treatment reduces risk of HCC, few studies quantify the impact of treatment on long-term risk in the era of direct-acting antivirals (DAA). Using data from the Chronic Hepatitis Cohort Study, we evaluated the impact of treatment type (DAA, interferon-based [IFN], or none) and outcome (sustained virological response [SVR] or treatment failure [TF]) on risk of HCC. We then developed and validated a predictive risk model. 17186 HCV patients were followed until HCC, death or last follow-up. We used extended landmark modelling, with time-varying covariates and propensity score justification and generalized estimating equations with a link function for discrete time-to-event data. Death was considered a competing risk. We observed 586 HCC cases across 104,000 interval-years of follow-up. SVR from DAA or IFN-based treatment reduced risk of HCC (aHR 0.13, 95% CI 0.08-0.20; and aHR 0.45, 95% CI 0.31-0.65); DAA SVR reduced risk more than IFN SVR (aHR 0.29, 95% CI 0.17-0.48). Independent of treatment, cirrhosis was the strongest risk factor for HCC (aHR 3.94, 95% CI 3.17-4.89 vs. no cirrhosis). Other risk factors included male sex, White race and genotype 3. Our six-variable predictive model had 'excellent' accuracy (AUROC 0.94) in independent validation. Our novel landmark interval-based model identified HCC risk factors across antiviral treatment status and interactions with cirrhosis. This model demonstrated excellent predictive accuracy in a large, racially diverse cohort of patients and could be adapted for 'real world' HCC monitoring.
MeSH term(s)	Humans ; Male ; Carcinoma, Hepatocellular/epidemiology ; Carcinoma, Hepatocellular/etiology ; Carcinoma, Hepatocellular/prevention & control ; Antiviral Agents/therapeutic use ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Liver Neoplasms/etiology ; Liver Neoplasms/complications ; Cohort Studies ; Risk Assessment ; Sustained Virologic Response ; Liver Cirrhosis/complications ; Hepatitis C/drug therapy
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2023-07-06
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	1212497-7
ISSN	1365-2893 ; 1352-0504
ISSN (online)	1365-2893
ISSN	1352-0504
DOI	10.1111/jvh.13859
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Zs.A 4119: Show issues

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Article ; Online: Real-World Safety and Effectiveness of an 8-Week Regimen of Glecaprevir/Pibrentasvir in Patients with Hepatitis C and Cirrhosis.

Lu, Mei / Rupp, Loralee B / Melkonian, Christina / Trudeau, Sheri / Daida, Yihe G / Schmidt, Mark A / Gordon, Stuart C

Advances in therapy

2024 Volume 41, Issue 2, Page(s) 744–758

Abstract: ... for treatment of chronic hepatitis C (HCV) in patients with cirrhosis. We used data from the Chronic Hepatitis ...

Abstract	Introduction: In 2019, an 8-week regimen of glecaprevir/ pibrentasvir (GLE/PIB) was FDA-approved for treatment of chronic hepatitis C (HCV) in patients with cirrhosis. We used data from the Chronic Hepatitis Cohort Study (CHeCS) to evaluate treatment response and adverse events among patients with HCV and cirrhosis under routine clinical care. Methods: Using an intention-to-treat (ITT)/modified ITT (mITT) approach, endpoints were (1) sustained virological response (SVR) at 12 weeks (SVR12) post-treatment; and (2) adverse events (AEs)/serious AEs during treatment. Patients with cirrhosis from two CHeCS sites were included if they were prescribed GLE/PIB from August 2017 to June 2020. Detailed treatment and clinical data were collected. Patient baseline characteristics were described with mean/standard deviation (std) for continuous variables, and proportions for categorical variables. Analyses were propensity score adjusted. The final model retained variables that were significant with p value < 0.05. Results: The ITT sample included 166 patients, with 43, 116, and 7 patients in the 8-week, 12-week, and > 12-week planned treatment groups. Among them, 159 had confirmed SVR (95.8%, LCL 93.2%). The mITT analysis included 160 patients after excluding 6 with unknown HCV RNA results; 159 achieved SVR (99.4%, LCL 98.3%). There were no significant differences in rates of SVR between the 8-week and 12-week regimens in either analysis, nor any association with patient characteristics. SAEs were experienced by 1 patient (2%) in the 8-week group, 7 (5%) in the 12-week group (including one death), and 2 (29%) in the > 12-week group; 4 patients (from the 12-week group) experienced serious AEs or hepatic events that were "likely attributable" to GLE/PIB treatment. Conclusion: An 8-week regimen of GLE/PIB is well tolerated and highly effective among US patients with HCV and cirrhosis receiving routine clinical care.
MeSH term(s)	Humans ; Cohort Studies ; Treatment Outcome ; Liver Cirrhosis/complications ; Liver Cirrhosis/drug therapy ; Quinoxalines/adverse effects ; Pyrrolidines/therapeutic use ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/genetics ; Hepacivirus/genetics ; Antiviral Agents/adverse effects ; Genotype ; Sulfonamides ; Aminoisobutyric Acids ; Lactams, Macrocyclic ; Cyclopropanes ; Leucine/analogs & derivatives ; Benzimidazoles ; Proline/analogs & derivatives
Chemical Substances	glecaprevir (K6BUU8J72P) ; pibrentasvir (2WU922TK3L) ; Quinoxalines ; Pyrrolidines ; Antiviral Agents ; Sulfonamides ; Aminoisobutyric Acids ; Lactams, Macrocyclic ; Cyclopropanes ; Leucine (GMW67QNF9C) ; Benzimidazoles ; Proline (9DLQ4CIU6V)
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	632651-1
ISSN	1865-8652 ; 0741-238X
ISSN (online)	1865-8652
ISSN	0741-238X
DOI	10.1007/s12325-023-02748-y
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Zs.A 2101: Show issues

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Article ; Online: Development of Negative Controls for Fc-C-Type Lectin Receptor Probes.

Hatinguais, Rémi / Kay, Madalaine / Salazar, Fabián / Conn, Daniel P / Williams, David L / Cook, Peter C / Willment, Janet A / Brown, Gordon D

Microbiology spectrum

2023 Volume 11, Issue 3, Page(s) e0113523

Abstract: Fc-C-type lectin receptor (Fc-CTLRs) probes are soluble chimeric proteins constituted ...

Abstract	Fc-C-type lectin receptor (Fc-CTLRs) probes are soluble chimeric proteins constituted of the extracellular domain of a CTLR fused with the constant fraction (Fc) of the human IgG. These probes are useful tools to study the interaction of CTLRs with their ligands, with applications similar to those of antibodies, often in combination with widely available fluorescent antibodies targeting the Fc fragment (anti-hFc). In particular, Fc-Dectin-1 has been extensively used to study the accessibility of β-glucans at the surface of pathogenic fungi. However, there is no universal negative control for Fc-CTLRs, making the distinction of specific versus nonspecific binding difficult. We describe here 2 negative controls for Fc-CTLRs: a Fc-control constituting of only the Fc portion, and a Fc-Dectin-1 mutant predicted to be unable to bind β-glucans. Using these new probes, we found that while Fc-CTLRs exhibit virtually no nonspecific binding to Candida albicans yeasts, Aspergillus fumigatus resting spores strongly bind Fc-CTLRs in a nonspecific manner. Nevertheless, using the controls we describe here, we were able to demonstrate that A. fumigatus spores expose a low amount of β-glucan. Our data highlight the necessity of appropriate negative controls for experiments involving Fc-CTLRs probes.
MeSH term(s)	Humans ; Lectins, C-Type/genetics ; Lectins, C-Type/metabolism ; Ligands ; Aspergillus fumigatus/genetics ; Aspergillus fumigatus/metabolism ; Fungi/metabolism ; Yeasts ; Spores, Fungal/metabolism ; beta-Glucans/metabolism
Chemical Substances	Lectins, C-Type ; Ligands ; beta-Glucans
Language	English
Publishing date	2023-05-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.01135-23
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Article ; Online: Cyclopentenylcytosine (CPE-C)

Eric G. Romanowski / Kathleen A. Yates / Y. Jerold Gordon

Molecules, Vol 28, Iss 5078, p

In Vitro and In Vivo Evaluation as an Antiviral against Adenoviral Ocular Infections

2023 Volume 5078

Abstract: ... approved antiviral treatment for these eye infections. Cyclopentenylcytosine (CPE-C) is an antiviral ... to determine the in vitro and in vivo antiviral activity of CPE-C as well as its ocular toxicity. Antiviral ... determined in uninfected rabbit eyes following topical ocular application. The in vitro EC50s for CPE-C ...

Abstract	Adenoviruses are the major cause of ocular viral infections worldwide. Currently, there is no approved antiviral treatment for these eye infections. Cyclopentenylcytosine (CPE-C) is an antiviral that has demonstrated activity against more than 20 viruses. The goals of the current study were to determine the in vitro and in vivo antiviral activity of CPE-C as well as its ocular toxicity. Antiviral activity was evaluated in vitro using standard plaque reduction assays to determine the 50% effective concentrations (EC 50 s) and in vivo in the Ad5/NZW rabbit ocular replication model. Ocular toxicity was determined in uninfected rabbit eyes following topical ocular application. The in vitro EC50s for CPE-C ranged from 0.03 to 0.059 μg/mL for nine adenovirus types that commonly infect the eye. Ocular toxicity testing determined CPE-C to be non-irritating or practically non-irritating by Draize scoring. In vivo, 3% CPE-C topically administered 4X or 2X daily for 7 days to adenovirus-infected eyes demonstrated effective antiviral activity compared with the negative control and comparable antiviral activity to the positive control, 0.5% cidofovir, topically administered twice daily for 7 days. We conclude CPE-C was relatively non-toxic to rabbit eyes and demonstrated potent anti-adenoviral activity in vitro and in vivo.
Keywords	antiviral ; adenovirus ; cyclopentenylcytosine ; eye ; conjunctivitis ; in vitro ; Organic chemistry ; QD241-441
Subject code	570
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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