scholarly journals Chitinase 3-like-1 contributes to acetaminophen-induced liver injury by promoting hepatic platelet recruitment

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Zhao Shan ◽  
Leike Li ◽  
Constance Lynn Atkins ◽  
Meng Wang ◽  
Yankai Wen ◽  
...  
Keyword(s):  
Liver Injury ◽  
Tissue Injury ◽  
Medical Center ◽  
Critical Role ◽  
The United States ◽  
Veterans Affairs ◽  
United States Government ◽  
Department Of Veterans Affairs ◽  
Platelet Accumulation ◽  
The Impact

Background: Hepatic platelet accumulation contributes to acetaminophen (APAP)-induced liver injury (AILI). However, little is known about the molecular pathways involved in platelet recruitment to the liver and whether targeting such pathways could attenuate AILI.Methods: Mice were fasted overnight before i.p. injected with APAP at a dose of 210 mg/kg for male mice and 325 mg/kg for female mice. Platelets adherent to Kupffer cells were determined in both mice and patients overdosed with APAP. The impact of α-Chi3l1 on alleviation of AILI was determined in a therapeutic setting, and liver injury was analyzed. Results: The present study unveiled a critical role of chitinase 3-like-1 (Chi3l1) in hepatic platelet recruitment during AILI. Increased Chi3l1 and platelets in the liver were observed in patients and mice overdosed with APAP. Compared to wild-type (WT) mice, Chil1-/- mice developed attenuated AILI with markedly reduced hepatic platelet accumulation. Mechanistic studies revealed that Chi3l1 signaled through CD44 on macrophages to induce podoplanin expression, which mediated platelet recruitment through C-type lectin-like receptor 2. Moreover, APAP treatment of Cd44-/- mice resulted in much lower numbers of hepatic platelets and liver injury than WT mice, a phenotype similar to that in Chil1-/- mice. Recombinant Chi3l1 could restore hepatic platelet accumulation and AILI in Chil1-/- mice, but not in Cd44-/- mice. Importantly, we generated anti-Chi3l1 monoclonal antibodies and demonstrated that they could effectively inhibit hepatic platelet accumulation and AILI.Conclusions: we uncovered the Chi3l1/CD44 axis as a critical pathway mediating APAP-induced hepatic platelet recruitment and tissue injury. We demonstrated the feasibility and potential of targeting Chi3l1 to treat AILI. Funding: ZS received funding from NSFC (32071129). FWL received funding from NIH (GM123261). ALFSG received funding from NIDDK (DK 058369). ZA received funding from CPRIT (RP150551 and RP190561) and the Welch Foundation (AU-0042-20030616). C.J. received funding from NIH (DK122708, DK109574, DK121330, and DK122796) and support from a University of Texas System Translational STARs award. Portions of this work was supported with resources and the use of facilities of the Michael E. DeBakey VA Medical Center and funding from Department of Veterans Affairs I01 BX002551 (Equipment, Personnel, Supplies). The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

Website Accessibility: U.S. Veterans Affairs Medical Centers as a Case Study

2018 ◽  
Vol 81 (4) ◽  
pp. 440-461 ◽  
Author(s):  
Norman E. Youngblood ◽  
Michael Brooks
Keyword(s):  
Medical Center ◽  
Information Source ◽  
The United States ◽  
Veterans Affairs ◽  
Department Of Veterans Affairs ◽  
Section 508 ◽  
Wcag 2.0 ◽  
Accessibility Issues ◽  
Veterans Affairs Medical Centers

The Internet is a critical eHealth/eGovernment information source, and the U.S. Department of Veterans Affairs operates the United States’ largest integrated health care system. This case study used machine-based accessibility testing to assess accessibility for 116 VA Medical Center websites, based on U.S. Section 508 standards and international WCAG 2.0 guidelines. While we found accessibility issues on each website analyzed, problems were generally limited. Notable exceptions included PDF accessibility and fixed-text sizes. The study’s results offer implications for practitioners (accessibility problems likely overlooked and ways to check accessibility) and educators, particularly the need to better integrate accessibility into the curriculum.

scholarly journals 1106 Associations Between Severe Mental Illness and Positive Airway Adherence in a Veteran Cohort

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A420-A421
Author(s):  
A M May ◽  
K Gandotra ◽  
G E Jaskiw
Keyword(s):  
United States ◽  
Mental Illness ◽  
Major Depression ◽  
The United States ◽  
Veterans Affairs ◽  
Sensitivity Analyses ◽  
United States Government ◽  
Department Of Veterans Affairs ◽  
Targeted Interventions ◽  
Improve Health

Abstract Introduction Serious mental illness (SMI) is associated with excess morbidity and mortality irrespective of healthcare access. Adherence differences may contribute to this health disparity. In those with sleep disorders, adherence to positive airway pressure (PAP) can improve health outcomes. We hypothesized that SMI is associated with lower PAP adherence. Methods In this retrospective cohort study, 5047 veterans receiving a PAP machine from the VANEOHS (1/1/2010 - 6/31/2015) were evaluated for 90-day PAP adherence (% days used ≥4 hours). A composite variable of any billing diagnosis of psychotic spectrum disorder, bipolar disorder, post-traumatic stress disorder (PTSD), or major depression was examined via linear regression. Analyses were adjusted for demographics, comorbidities, and medications. We conducted sensitivity analyses of 30-day adherence as well as subset analyses of associations between each disorder and adherence. Results The group was 38.8 ± 11.9 years old, 3.9% female with 52.6% with major depression, 25.0% with PTSD. 58.4% of the cohort had at least one psychiatric disorder. PTSD with depression was the most common comorbidity in those with two or more psychiatric diagnoses. Unadjusted analyses showed worse adherence in those with any SMI (β = -7.5%, 95% CI: -9.8% -5.3%), which was mitigated in adjusted analyses (β = -1.6%, 95% CI: -5.1%, 1.9%). All individual SMIs were negatively associated with adherence, but only PTSD was associated with less adherence in adjusted analyses (β = -6.4%, 95%CI: -11.2%, -1.6%). Sensitivity analyses of 30-day adherence were similar to primary analyses. Conclusion In this large cohort of veterans, broadly defined SMI was associated with lower 30- and 90-day adherence in unadjusted but not adjusted analyses. Replication and refinement of the link between SMI, particularly PTSD, and adherence may provide opportunities for targeted interventions and improve health disparities. Support This work was supported in part by Career Development Award IK2CX001882 from the United States (U.S.) Department of Veterans Affairs Clinical Sciences Research and Development Service. The contents of this work do not represent the views of the Department of Veterans Affairs or the United States government.

453 Cost-Effectiveness of Requalifying for Positive Airway Pressure Treatment After Initial Nonadherence

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A179-A179
Author(s):  
Anna May ◽  
Lu Wang ◽  
Mendel Singer
Keyword(s):  
United States ◽  
Cost Effectiveness ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Cost Effective ◽  
The United States ◽  
Veterans Affairs ◽  
United States Government ◽  
Department Of Veterans Affairs ◽  
Current Policy

Abstract Introduction Obstructive sleep apnea (OSA) is effectively treated with continuous positive airway pressure (CPAP). However, many people are not able to become adherent in the initial 90-day trial window for this therapy. Medicare requires a polysomnography and repeat trial documenting adherence before continuing payment for these services. Oral appliance therapy (OAT) is also an OSA first-line therapy but is less effective than CPAP. Methods We created a decision tree to model 4 strategies over a 5-year time horizon: (1) current policy, (2) direct referral for CPAP equipment, (3) OAT followed by CPAP under current policy, and (4) OAT followed by direct CPAP referral in a the Medicare population with mild-moderate OSA and nonadherence to a first attempt at CPAP therapy. Medicare fee schedules in 2020 defined costs. Incremental cost-effectiveness (ICER) was used to identify the supreme strategy Results The current policy was the most expensive. Both the current policy and direct DME referral were dominated by starting with OAT. OAT followed by titration was the most cost-effective strategy with an ICER of $42,586.47. The ICER was sensitive to adherence in the direct CPAP strategy and probability of getting CPAP equipment (vs. lost to follow-up). Conclusion Starting with OAT therapy in those that were CPAP nonadherent on first attempt is cost-effective. Despite decreased effectiveness, the increase adherence to OAT make it an attractive option for retrial of OSA therapy. If OAT therapy fails, the current policy is more cost-effective than direct CPAP referral. Support (if any) This study was supported Career Development Award IK2CX001882 from the United States (U.S.) Department of Veterans Affairs Clinical Sciences Research and Development Service. The contents of this work do not represent the views of the Department of Veterans Affairs or the United States government.

Chitinase 3-like-1 Contributes to Acetaminophen-induced Liver Injury by Promoting Hepatic Platelet Recruitment

2021 ◽  
Author(s):  
Zhao Shan ◽  
Leike Li ◽  
Constance Lynn Atkins ◽  
Meng Wang ◽  
Yankai Wen ◽  
...  
Keyword(s):  
Liver Injury ◽  
Tissue Injury ◽  
Critical Role ◽  
Molecular Pathways ◽  
Mechanistic Studies ◽  
Wild Type ◽  
Critical Pathway ◽  
Podoplanin Expression ◽  
Platelet Accumulation

Hepatic platelet accumulation contributes to acetaminophen (APAP)-induced liver injury (AILI). However, little is known about the molecular pathways involved in platelet recruitment to the liver and whether targeting such pathways could attenuate AILI. The present study unveiled a critical role of chitinase 3-like-1 (Chi3l1) in hepatic platelet recruitment during AILI. Increased Chi3l1 and platelets in the liver were observed in patients and mice overdosed with APAP. Compared to wild-type (WT) mice, Chi3l1-/- mice developed attenuated AILI with markedly reduced hepatic platelet accumulation. Mechanistic studies revealed that Chi3l1 signaled through CD44 on macrophages to induce podoplanin expression, which mediated platelet recruitment through C-type lectin-like receptor 2. Moreover, APAP treatment of CD44-/- mice resulted in much lower numbers of hepatic platelets and liver injury than WT mice, a phenotype similar to that in Chi3l1-/- mice. Recombinant Chi3l1 could restore hepatic platelet accumulation and AILI in Chi3l1-/- mice, but not in CD44-/- mice. Importantly, we generated anti-Chi3l1 monoclonal antibodies and demonstrated that they could effectively inhibit hepatic platelet accumulation and AILI. Overall, we uncovered the Chi3l1/CD44 axis as a critical pathway mediating APAP-induced hepatic platelet recruitment and tissue injury. We demonstrated the feasibility and potential of targeting Chi3l1 to treat AILI.

scholarly journals Communications and Screening for 2019 Novel Coronavirus at a Tertiary-Care Medical Center

2020 ◽  
Vol 41 (S1) ◽  
pp. s84-s84
Author(s):  
Lorinda Sheeler ◽  
Mary Kukla ◽  
Oluchi Abosi ◽  
Holly Meacham ◽  
Stephanie Holley ◽  
...  
Keyword(s):  
Screening Tool ◽  
Medical Center ◽  
Academic Medical Center ◽  
Tertiary Care ◽  
The United States ◽  
World Health ◽  
Communication Campaign ◽  
Electronic Screening ◽  
Novel Coronavirus ◽  
The Impact

Background: In December of 2019, the World Health Organization reported a novel coronavirus (severe acute respiratory coronavirus virus 2 [SARS-CoV-2)]) causing severe respiratory illness originating in Wuhan, China. Since then, an increasing number of cases and the confirmation of human-to-human transmission has led to the need to develop a communication campaign at our institution. We describe the impact of the communication campaign on the number of calls received and describe patterns of calls during the early stages of our response to this emerging infection. Methods: The University of Iowa Hospitals & Clinics is an 811-bed academic medical center with >200 outpatient clinics. In response to the coronavirus disease 2019 (COVID-19) outbreak, we launched a communications campaign on January 17, 2020. Initial communications included email updates to staff and a dedicated COVID-19 webpage with up-to-date information. Subsequently, we developed an electronic screening tool to guide a risk assessment during patient check in. The screening tool identifies travel to China in the past 14 days and the presence of symptoms defined as fever >37.7°C plus cough or difficulty breathing. The screening tool was activated on January 24, 2020. In addition, university staff contacted each student whose primary residence record included Hubei Province, China. Students were provided with medical contact information, signs and symptoms to monitor for, and a thermometer. Results: During the first 5 days of the campaign, 3 calls were related to COVID-19. The number of calls increased to 18 in the 5 days following the implementation of the electronic screening tool. Of the 21 calls received to date, 8 calls (38%) were generated due to the electronic travel screen, 4 calls (19%) were due to a positive coronavirus result in a multiplex respiratory panel, 4 calls (19%) were related to provider assessment only (without an electronic screening trigger), and 2 calls (10%) sought additional information following the viewing of the web-based communication campaign. Moreover, 3 calls (14%) were for people without travel history but with respiratory symptoms and contact with a person with recent travel to China. Among those reporting symptoms after travel to China, mean time since arrival to the United States was 2.7 days (range, 0–11 days). Conclusion: The COVID-19 outbreak is evolving, and providing up to date information is challenging. Implementing an electronic screening tool helped providers assess patients and direct questions to infection prevention professionals. Analyzing the types of calls received helped tailor messaging to frontline staff.Funding: NoneDisclosures: None

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