Faculty Bibliography

OBJECTIVES/OBJECTIVE:To describe the distribution of laboratory values for nonstandard inflammatory and cardiac biomarkers in otherwise healthy children presenting to the pediatric emergency department (PED) with fever and viral or nonspecific illness. METHODS:Single-center retrospective study of otherwise healthy children 3 months to 20 years presenting to the PED with fever and had a laboratory evaluation for multisystem inflammatory syndrome in children (MIS-C) between April 15, 2020 and January 24, 2022. All patients had NT-pro-b-natriuretic peptide (NT-proBNP) or troponin obtained (as part of an institutional pathway for MIS-C evaluation) during this period. Children with comorbidities, MIS-C, Kawasaki disease, myocarditis, or definitive non-viral illness were excluded. We summarized d-dimer, ferritin, troponin, and NT-proBNP distributions using descriptive statistics. One-way analysis of variance tested for differences among 3 disease categories: non-SARS-CoV-2 viral illness, fever not otherwise specified (NOS), and SARS-CoV-2 infection. Outlier values were identified as three times the interquartile range above the third quartile on box-and-whisker plots. RESULTS:Of 134 eligible patients, 50, 65, and 19 were categorized as non-SARS-CoV-2 viral illness, fever NOS, and SARS-CoV-2 positive illness, respectively. Median age was 2 years. Median fever duration was 4 days, with 124/134 (93%) described as well-appearing and 112/134 (84%) discharged home. The median values for all biomarkers were within institutional laboratory reference ranges, with all distributions skewed to lower values, and without statistically significant differences between disease categories (P > 0.05). D-dimer values were above the institutional reference range in 43/97 (44%), ferritin was above the reference range in 24/114 (21%), NT-proBNP was above the reference range in 26/123 (21%), and troponin levels were outside the range in 4/123 (3%). Thirteen patients had extreme outlier values. CONCLUSIONS:Otherwise healthy children presenting to the PED with a fever and viral or nonspecific illnesses may frequently have elevated serum d-dimer, ferritin, and NT-proBNP above institutional reference ranges. Troponin elevation was infrequent.

BACKGROUND:Some pulse oximeters perform worse in people with darker skin, and this may be due to inadequate diversity of skin pigment in device development study cohorts. Guidance is needed to accurately and equitably characterize skin pigment to ensure diversity in research cohorts. We tested multiple methods for characterizing skin pigment to assess comparability and impact on cohort diversity. OBJECTIVES/OBJECTIVE:Assess reliability and comparability of common skin pigment measurement methods Compare findings from different anatomical sites Demonstrate that pigment cannot be assumed from US National Institutes for Health (NIH) race categories. METHODS:We used three subjective methods (perceived Fitzpatrick pFP, Monk Skin Tone MST and Von Luschan VL) and two objective methods (Konica Minolta CM-700d spectrophotometer and Delfin Skin Color Catch DSCC colorimeter) for individual typology angle (ITA), across multiple measurement sites in adults. We calculated ΔE to estimate operator perceptibility thresholds for subjective methods and to determine reproducibility for objective methods. We used each method to categorize participants as 'light, medium, or dark' and compared the impact of method selection on cohort diversity. RESULTS:We studied 789 participants, with 33,856 assessments. The MST had the widest luminosity range, and VL had the least discernible adjacent categories. With 'dark' defined as ITA <-30°, 14% of participants were categorized 'dark' as compared to 26% by pFP or 16% by MST. Approximately half of the 'dark' cohort had an ITA <-50°. With an ITA threshold <-50°, only 7% of the cohort was categorized as 'dark.' When 'Black or African American' self-identification was used to define 'dark', 23% of the cohort was categorized as such. Each self-assigned NIH race category included a wide range of ITA and subjective scale categories. Both ITA and L* from the KM-700d and DSCC demonstrated strong correlation (⍴ > 0.7). CONCLUSION/CONCLUSIONS:Common methods for skin pigment characterization, especially the use of race or subjective scales, have significant limitations. When applied to the same cohort, different methods yield significantly different results, and some may overestimate diversity. Previously published ITA thresholds for defining 'dark' skin are too light and lead to underrepresentation of people with darker skin.

Adipose tissue has emerged as a central regulator of human physiology, with its dysfunction driving the global rise in obesity-associated diseases, such as type 2 diabetes, cardiovascular and liver diseases, and several cancers. Once thought to be inert, adipocytes are now recognized as dynamic, responsive cells essential for energy homeostasis and interorgan communication, including the brain. Distinct adipose depots support specialized functions across development, sex, and aging. Technologies like single-cell RNA sequencing are unraveling depot-specific mechanisms, with the potential of identifying new therapeutic targets. This review highlights major scientific advancements leading to our current appreciation of the pivotal role of adipose tissue in health and disease. Many key discoveries in this field have been catalyzed by National Institutes of Health funding, particularly through the National Institute of Diabetes, Digestive and Kidney Diseases, now celebrating its 75th anniversary.

High-grade serous ovarian carcinoma (HGSC) remains an incompletely understood, highly lethal disease. Historically, a lack of fidelitous in vitro and in vivo models representing HGSC biology and therapy response has been a major barrier to progress. As we discuss below, multiple (if not most) early studies used-and some investigators continue to use-human "ovarian cancer cell lines" that lack key genomic/genetic features of HGSC, rendering their conclusions questionable. The frequently deployed ID8 syngeneic mouse model is similarly suspect, as it derives from ovarian surface epithelium (OSE) and is Trp53 wild-type. In contrast, most, if not all, HGSC arises in fallopian tube epithelium (FTE), and bona fide HGSC is universally TP53 mutant or silenced. Over the past 10 years, attempts have been made to rectify these historical deficiencies, including careful assessment of the genetic composition of standard ovarian cancer cell lines and the development of mouse and human organoids, genetically engineered mouse models (GEMMs), and patient-derived xenografts (PDXs). In this review, we discuss these advances, exploring their differences, strengths, and weaknesses. We also describe "next-generation" approaches to more faithfully model HGSC cells in the context of a more realistic tumor microenvironment.

OBJECTIVE:To assess the environmental impact of radiography and fluoroscopy, using life cycle assessment (LCA), focusing on energy use and emissions. METHODS:This ISO 14040-guided LCA-based study focused on radiography and fluoroscopy services, including the production and use of two radiography and two fluoroscopy machines, at a quaternary care 800-bed academic medical center in the Southeastern United States over a 1-year period. Data were collected through direct observation, record review, staff interviews, and energy metering. Environmental impacts were assessed using SimaPro 9.3.0.2 and the Ecoinvent v3.8 database. RESULTS:e per scan). Medical linens or textiles accounted for 24% of total emissions. Other significant environmental impacts included ozone depletion, smog, acidification, and eutrophication. DISCUSSION/CONCLUSIONS:Reducing energy consumption by decarbonizing electricity sources and optimizing equipment use can significantly decrease greenhouse gas emissions. Implementing sustainable practices in linen use, procurement, and end-of-life management is also crucial. Reducing low-value imaging can further mitigate environmental impact.