Citations

ABSTRACT Introduction: Little is known regarding peripheral blood mononuclear cell telomere length (PBMC-TL) and response to traumatic injury. The objective of this study was to characterize the role of PBMC-TL in coagulation and clinical outcomes after injury. Methods: Plasma and buffy coats were prospectively collected from trauma patients and healthy volunteers. DNA was purified and PBMC-TL quantified by quantitative polymerase chain reaction. Thrombin generation kinetics were expressed as lag time (in minutes), peak height (in nanometers), time to peak (in minutes), and endogenous thrombin potential (in nM × min). Results are in median and quartiles [Q1, Q3]. P < 0.05 was considered significant (Wilcoxon rank sum testing). Results: Forty-two younger patients (21 [20, 22] years, 69% were male) and 39 older patients (62 [61, 64] years, 79% were male) were included. There was no significant difference in Clinical Frailty Scores between groups. Younger patients had longer total PBMC-TL (0.40 Mb [0.30, 0.49] vs. 0.29 Mb [0.23, 0.33], P < 0.001) and longer average PBMC-TL per chromosome (4.3 kb [3.3, 5.3] vs. 3.2 kb [2.5, 3.7], P < 0.001). When older patients were stratified by 50th percentile of PBMC-TL, there were no differences in thrombin generation; however, those with shorter telomeres were less likely to be discharged home (29% vs. 77%, P = 0.004). Older patients in the bottom quartile of PBMC-TL had shorter lag time (2.78 min [2.33, 3.00] vs. 3.33 min [3.24, 3.89], P = 0.030) and were less likely to be discharged home (22% vs. 90%, P = 0.006) than those in the top quartile of PBMC-TL. Multivariable logistic regression models revealed both increased age and shorter PBMC-TL to be independent predictors of discharge disposition other than home. Conclusion: In older trauma patients, shorter PBMC-TL is associated with accelerated initiation of thrombin generation and lower likelihood of being discharged to home.

Abstract Purpose: The purpose of this study was to evaluate the feasibility and specimen quality of lymph node biopsies prepared through a novel automated system for automated fixation, drying and staining compared to standard slide preparation method. Methods: We performed a prospective, single-center study of patients undergoing endobronchial ultrasound. Samples were split into conventional standard of care (SOC) slide preparation and preparation using the device (ASP). Pathologists compared the SOC slides to the slides prepared by the automated system and assessed the following metrics: nuclear and cytoplasmic quality, presence of debris/artifact, staining quality, creation of a monolayer, and ease of adequacy/diagnosis assessment. A score between 1 (lowest quality) and 3 (highest quality) was assigned to the above metrics. Results: 60 patients were recruited. One to three lymph nodes were sampled for each patient with a total of 73 samples collected. The mean scores of each assessment category showed no statistical difference between the two preparation techniques except for improved monolayer creation in the ASP samples. All samples showed diagnostic equivalency between the automated slides and conventional slides except for one which was reported to be suspicious on the ASP sample and atypical on the SOC. Conclusion: Study results suggest that slides prepared by the automated system are of adequate quality for adequacy assessment with diagnostic concordance when compared to SOC slides.

Abstract Ovarian carcinosarcoma (OCS) is an aggressive and rare tumor type with limited treatment options. OCS is hypothesized to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analyzed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated that the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumors. Preclinical OCS models were used to test the efficacy of microtubule-targeting drugs, including eribulin, which has previously been shown to reverse EMT characteristics in breast cancers and induce differentiation in sarcomas. Vinorelbine and eribulin more effectively inhibited OCS growth than standard-of-care platinum-based chemotherapy, and treatment with eribulin reduced mesenchymal characteristics and N-MYC expression in OCS patient-derived xenografts. Eribulin treatment resulted in an accumulation of intracellular cholesterol in OCS cells, which triggered a downregulation of the mevalonate pathway and prevented further cholesterol biosynthesis. Finally, eribulin increased expression of genes related to immune activation and increased the intratumoral accumulation of CD8+ T cells, supporting exploration of immunotherapy combinations in the clinic. Together, these data indicate that EMT plays a key role in OCS tumorigenesis and support the conversion theory for OCS histogenesis. Targeting EMT using eribulin could help improve OCS patient outcomes. Significance: Genomic analyses and preclinical models of ovarian carcinosarcoma support the conversion theory for disease development and indicate that microtubule inhibitors could be used to suppress EMT and stimulate antitumor immunity.

Importance US rural vs nonrural populations have striking disparities in diabetes care. Whether rurality contributes to disparities in diabetes mortality is unknown. Objective To examine rates and trends in diabetes mortality based on county urbanization. Design, Setting, and Participants In this observational, cross-sectional study, the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database was searched from January 1, 1999, to December 31, 2018, for diabetes as a multiple cause and the underlying cause of death among residents aged 25 years or older in US counties. County urbanization was categorized as metro, medium-small, and rural. Weighted multiple linear regression models and jackknife resampling, with a 3-segment time component, were used. The models included exposures with up to 3-way interactions and were age standardized to the 2009-2010 population. The analyses were conducted from July 1, 2020, to February 1, 2022. Exposures County urbanization (metro, medium-small, or rural), gender (men or women), age group (25-54, 55-74, or ≥75 years), and region (Midwest, Northeast, South, or West). Main Outcomes and Measures Annual diabetes mortality rate per 100 000 people. Results From 1999-2018, based on 4 022 238 309 person-years, diabetes was a multiple cause of death for 4 735 849 adults aged 25 years or older. As a multiple cause, diabetes mortality rates in 2017-2018 vs 1999-2000 were highest and unchanged in rural counties (157.2 [95% CI, 150.7-163.7] vs 154.1 [95% CI, 148.2-160.1]; P = .49) but lower in medium-small counties (123.6 [95% CI, 119.6-127.6] vs 133.6 [95% CI, 128.4-138.8]; P = .003) and urban counties (92.9 [95% CI, 90.5-95.3] vs 109.7 [95% CI, 105.2-114.1]; P &lt; .001). In 2017-2018 vs 1999-2000, mortality rates were higher in rural men (+18.2; 95% CI, 14.3-22.1) but lower in rural women (−14.0; 95% CI, −17.7 to −10.3) ( P &lt; .001 for both). In the 25- to 54-year age group, mortality rates in 2017-2018 vs 1999-2000 showed a greater increase in rural counties (+9.4; 95% CI, 8.6-10.2) compared with medium-small counties (+4.5; 95% CI, 4.0-5.0) and metro counties (+0.9; 95% CI, 0.4-1.4) ( P &lt; .001 for all). Of all regions and urbanization levels, the mortality rate in 2017-2018 vs 1999-2000 was higher only in the rural South (+13.8; 95% CI, 7.6-20.0; P &lt; .001). Conclusions and Relevance In this cross-sectional study, US rural counties had the highest overall diabetes mortality rate. The determinants of persistent rural disparities, in particular for rural men and for adults in the rural South, require investigation.

Abstract Automated and accurate identification of refugees in healthcare databases is a critical first step to investigate healthcare needs of this vulnerable population and improve health disparities. In this study, we developed a machine‐learning method, named refugee identification system (RIS) to address this need. We curated a data set consisting of 103 refugees and 930 non‐refugees in Arizona. We compiled de‐identified individual‐level information including age, primary language, and noise‐masked home address, state‐level refugee resettlement statistics, and world language statistics. We then performed feature engineering to convert language and masked address into quantitative features. Finally, we built a random forest model to classify refugee and non‐refugees. RIS achieved high classification accuracy (overall accuracy=0.97, specificity=0.99, sensitivity=0.85, positive predictive value=0.88, negative predictive value=0.98, and area under receiver operating characteristic curve=0.98). RIS is customizable for refugee identification outside Arizona. Its application enables large‐scale investigation of refugee healthcare needs and improvement of health disparities.

AbstractBackground and AimsAlthough high‐resolution manometry (HR_ARM) is commonly used to diagnose defecatory disorders, its intraindividual day‐to‐day reproducibility is unknown. Since these measurements entail voluntary effort, this study aimed to evaluate the intraindividual day‐to‐day reproducibility of HR_ARM.MethodsIn 22 healthy women (35 years [14] mean [SD]) and 53 constipated patients (42 years [13], 46 women), the rectal balloon expulsion time (BET), and anorectal pressures were measured with HR_ARM on 2 days separated by a median (interquartile range) of 15 days (11–53) in healthy and 40 days (8–75) in constipated patients. Anorectal pressures were evaluated at rest (20 s), during squeeze, and during evacuation. Rectal sensation was also evaluated in constipated patients. The agreement between both measurements was evaluated with Lin's concordance correlation coefficient (CCC) and other tests.ResultsAmong constipated patients, the anal resting (mean CCC [95%CI] 0.62 [0.43–0.76]) and squeeze pressures (CCC 0.65 [0.47–0.79]), rectoanal gradient during evacuation (CCC 0.42 [0.17–0.62]), and rectal sensory thresholds (CCC for urgency 0.72 [0.52–0.84]) were concordant. Between days 1 and 2, one or more outcomes, characterized as normal or abnormal, differed in 79% of constipated patients, i.e., anal resting and squeeze pressures, the gradient, and the rectal BET differed in, respectively, 25%, 19%, 36%, and 10% of constipated patients. The rectal BET was prolonged in three healthy persons (both days) and either on 1 day (six patients) or 2 days (33 patients) in constipated patients.ConclusionsWhile HR_ARM variables and the BET are reproducible within healthy and constipated persons, the outcome on repeat testing differed in 79% of constipated patients.

Hospitalized patients are at an increased risk of malnutrition due to multiple factors including, but not limited to, acute and chronic diseases especially those affecting gastrointestinal tract, surgery, appetite, and frequent nil per os while undergoing diagnostic workup. Because of this, guidelines suggest the use of oral nutritional supplements (ONS) in hospitalized patients to reduce the risk of malnutrition and its complications. The current report aims to highlights key findings from a cross-sectional survey of 99 hospitalized patients who were at risk for or diagnosed with malnutrition and prescribed ONS. Data regarding ONS prescriber information as well as number ordered and consumed were collected. Of the 2.4 ± 1.5 supplements ordered per person each day, only 1.3 ± 1.1 were consumed, and there was 48% wastage of prescribed ONS. However, dietitian involvement was associated with significant reduction in wastage. Given the need and benefit, it is imperative for the nutrition community to further explore best practices to improve ONS consumption.