ScholarWorks IU Indianapolis
Not a member yet
51146 research outputs found
Sort by
The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia
Get PDFAlterations in bile acid profile and pathways contribute to hepatic inflammation in cancer cachexia, a syndrome worsening the prognosis of cancer patients. As the gut microbiota impinges on host metabolism through bile acids, the current study aimed to explore the functional contribution of gut microbial dysbiosis to bile acid dysmetabolism and associated disorders in cancer cachexia. Using three mouse models of cancer cachexia (the C26, MC38 and HCT116 models), we evidenced a reduction in the hepatic levels of several secondary bile acids, mainly taurodeoxycholic (TDCA). This reduction in hepatic TDCA occurred before the appearance of cachexia. Longitudinal analysis of the gut microbiota pinpointed an ASV, identified as Xylanibacter rodentium, as a bacterium potentially involved in the reduced production of TDCA. Coherently, stable isotope-based experiments highlighted a robust decrease in the microbial 7α-dehydroxylation (7α-DH) activity with no changes in the bile salt hydrolase (BSH) activity in cachectic mice. This approach also highlighted a reduced microbial 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 12α-hydroxysteroid dehydrogenase (12α-HSDH) activities in these mice. The contribution of the lower production of TDCA to cancer cachexia was explored in vitro and in vivo. In vitro, TDCA prevented myotube atrophy, whereas in vivo hepatic whole transcriptome analysis revealed that TDCA administration to cachectic mice improved the unfolded protein response and cholesterol homeostasis pathways. Coherently, TDCA administration reversed hepatic cholesterol accumulation in these mice. Altogether, this work highlights the contribution of the gut microbiota to bile acid dysmetabolism and the therapeutic interest of the secondary bile acid TDCA for hepatic cholesterol homeostasis in the context of cancer cachexia. Such discovery may prove instrumental in the understanding of other metabolic diseases characterized by microbial dysbiosis. More broadly, our work demonstrates the interest and relevance of microbial activity measurements using stable isotopes, an approach currently underused in the microbiome field
Implementing a biomarker‐enabled care pathway to accelerate identification of early‐stage Alzheimer’s disease in primary care
Get PDFBackground:
New blood‐based and digital biomarkers for Alzheimer’s disease (AD) make early detection possible at stages when novel, disease‐specific therapies are likely to be most effective. These approaches may offer less invasive, more cost‐effective alternatives to traditional methods such as cerebrospinal fluid (CSF) collection or positron emission tomography (PET) imaging for diagnosing and staging AD. Building care pathways leveraging blood‐based and digital biomarkers starts with understanding the current biomarker landscape and considering opportunities for widespread implementation in primary care clinical practice.
Methods:
A multidisciplinary team representing neurology, neuropsychology, geriatrics, primary care, epidemiology, laboratory programs, and patient advocacy was convened to review a summary of current biomarker research findings and discuss barriers and opportunities to implement biomarkers as part of an AD consensus‐driven clinical care pathway.
Results:
The emergence of biomarkers has shifted diagnosis from primarily clinical to a biological definition of AD. However, there is currently no consensus on where biomarkers fit within an AD care pathway and when they should be utilized in primary care or dementia specialist care settings.
We found a relative paucity of published data on biomarker test accuracy in diagnosis outside tightly controlled research settings, limiting guidance around how results should be interpreted and managed in real‐world care settings. Evidence gaps are especially pressing for heterogeneous, diverse populations under‐represented in AD research.
New biomedical therapies specific to the pathobiology of AD are driving research on blood and digital biomarkers to inform optimal ways to accelerate identification. As most individuals with AD are not evaluated by specialists, accurate and usable information about the place of biomarkers in the diagnosis and treatment of cognitive impairment must reach primary care
Conclusions:
With growing interest in the promise of non‐invasive biomarkers to improve detection, differentiation, and diagnosis of AD, new research is needed to generate real‐world evidence about their performance across populations, how to interpret results, and how best to use them in patient management. Effective educational strategies are needed to disseminate high‐quality evidence that engages primary care and healthcare delivery systems in implementing optimal clinical pathways. More detailed learnings for successful care pathway implementation will be shared
Drug‐Induced Liver Injury in Patients With Chronic Liver Disease
No full textObjective: Drug-induced liver injury (DILI) is a global problem and can develop from exposure to prescription or over-the-counter medications as well as herbal and dietary supplements. The diagnosis of DILI is clinically challenging, and liver injury can be severe leading to liver failure, death, or liver transplantation. Patients with underlying chronic liver diseases (CLD) may be at increased risk for DILI, which is associated with factors related to drug or liver disease.
Methods: This review summarises current knowledge on the risk and outcomes of DILI in patients with CLD.
Results: Patients with CLD may be at an increased risk for DILI. Additionally patients with underlying CLD are at risk for more severe liver injury and worse outcomes after DILI.
Discussion: The risk for and poor outcomes from DILI are accentuated in patients with CLD and potentially leading to the worst-case scenario of acute-on-chronic liver failure. We highlight the key observations on DILI with a broad range of underlying liver diseases and the high-DILI risk agents implicated in those populations
Emergency Medicine Faculty Utilization of Point-of-Care Ultrasound in the Clinical Setting
Get PDFIntroduction:
Point-of-care ultrasound (POCUS) curricula for emergency medicine residents and faculty are guided by emergency medicine societal ultrasound guidelines. These guidelines lack clinical data to support them and are mainly based on expert consensus recommendations. Data are needed to address critical gaps in the literature to identify which POCUS studies are most commonly utilized in the clinical setting to help guide guideline recommendations and POCUS curricular design. The primary aim of this study was to determine the most utilized POCUS modalities in the emergency department clinical setting. The findings of this study may be used to guide the curricular design of future POCUS trainings.
Methods:
This was a retrospective study evaluating all clinically indicated and billed POCUS studies performed and interpreted by faculty in the emergency department setting across 10 emergency departments over a three-year period in Indianapolis, Indina, USA. The number of exams and modalities were extracted from the POCUS workflow solution. The frequency and percentage of exams were calculated.
Results:
A total of 5,324 POCUS examinations were performed. Cardiac, obstetric, soft tissue, and focused assessment with sonography in trauma (FAST) POCUS were the most billed modalities across all adult emergency departments regardless of academic or community setting. Although fewer data were available from the pediatric setting, we found that cardiac, soft tissue, FAST, and lung POCUS exams were the most utilized.
Conclusion:
These data from a single healthcare system would suggest that emergency physician POCUS curricula should focus on cardiac, obstetric, soft tissue, FAST, and lung exams. More data are needed from the pediatric setting to determine which scans are most utilized
2025 Indiana Libraries and Literacy Symposium Impact Report
Get PDFThe Indiana Libraries and Literacy Symposium provides an opportunity for Indiana librarians, educators, and literacy advocates to network and learn more about a specific literacy topic each year. This report details the impact of this year's Symposium which focused on gaming and play literacy
A retrospective review of psychosocial correlates of chronic pain in cisgender, transgender, and gender-diverse youth receiving evaluation in interdisciplinary pediatric pain clinics
No full textBackground: Individuals who experience social marginalization, such as transgender and gender-diverse (TGD) youth, have increased risk for poor health outcomes, including chronic pain. A better understanding of the impact of chronic pain in these populations would improve treatment and aid in reducing health care disparities. Our retrospective review of clinical data examined psychosocial correlates of pain in TGD and cisgender youth with chronic pain.
Aims: The study aim was to explore differences in psychosocial variables between TGD and cisgender youth with chronic pain. In alignment with the minority stress model, we hypothesized worse pain and pain-related disability, poorer quality of life, and more internalizing symptoms in TGD patients. The secondary aim was to explore associations among psychosocial variables in TGD and cisgender youth.
Methods: Data were collected from 140 youth (48 TGD, 92 cisgender) evaluated in pediatric pain clinics. Independent samples t-tests examined group differences in pain intensity, functional disability, quality of life, pain catastrophizing, and internalizing symptoms. Bivariate correlations were conducted for each group, and differences in the strength of correlations were evaluated using Fisher r-to-z. Institutional review board (IRB) approval was obtained for all study procedures at each participating institution prior to extraction of retrospective clinical data (Indiana 240 University IRB Protocol No. 12506, The Ohio State University College of Medicine IRB Protocol No. 16-00937). Informed consent was not required or obtained due to the retrospective nature of the study.
Results: Cisgender patients reported worse pain intensity, whereas TGD patients reported lower quality of life and more internalizing symptoms. In the combined sample, pain intensity was correlated with worse functional disability, poorer quality of life, and more catastrophic thinking. No group differences in the strength of correlations were found.
Conclusions: Results suggest that for TGD youth with chronic pain, internalizing symptoms and quality of life are important targets for treatment and improvement
Phoenix Sepsis Criteria in Critically Ill Children: Retrospective Validation Using a United States Nine-Center Dataset, 2012–2018
Get PDFObjectives: To perform: 1) external validation of the Phoenix Sepsis Score and Phoenix sepsis criteria in a multicenter cohort of critically ill children with infection and a comparison with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria; 2) a study of Phoenix sepsis criteria performance in patient subgroups based on age and comorbidities; 3) an assessment of microbiological profile of children with Phoenix sepsis; and 4) a study of the performance of the Phoenix-8 score.
Design: Secondary, retrospective analysis of a multicenter cohort study from 2012 to 2018.
Setting: Nine PICUs in the United States.
Patients: PICU admissions with suspected infection.
Interventions: None.
Measurements and main results: Among 25,680 encounters of children with suspected or confirmed infection on PICU admission (4.6% in-hospital mortality), 11,168 (43%) met Phoenix criteria for sepsis or septic shock (9% in-hospital mortality). The Phoenix criteria generally outperformed the IPSCC criteria at discriminating mortality in all critically ill children with infections and across all subgroup analyses, including age group, malignancy, or technology dependence. Of 11,168 patients who met Phoenix criteria, 28% were negative for IPSCC criteria for sepsis and these had higher in-hospital mortality than those who met IPSCC sepsis criteria but not Phoenix criteria (4.7% vs.1.7%; p < 0.001), which was similar to the mortality of patients without sepsis (1.3%). Sepsis was associated with respiratory or bloodstream infection, most commonly Pseudomonas aeruginosa or Staphylococcus aureus. The Phoenix-8 score had good discrimination of mortality in children with infections, comparable to or better than validated and widely used severity of illness and organ dysfunction scores.
Conclusions: In 2012-2018, among U.S. patients with suspected or confirmed infection admitted to nine PICUs, those with the highest risk of mortality can be identified using the Phoenix sepsis criteria, including in children of different age groups and those with major comorbidities