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Background and aims: Reliable lead screening methods are necessary to support early identification of lead exposure in children. Sample collection using dried blood spots (DBS) offers advantages compared to traditional venipuncture and capillary collection. Here, we describe and compare three lead DBS inductively coupled plasma-mass spectrometry (ICP-MS) methods for lead screening. Materials and methods: Lead was extracted from Whatman 903 protein saver cards punches and analyzed by ICP-MS across three independent clinical laboratories. Each laboratory evaluated the performance of aqueous and matrix-matched DBS calibrators using external quality control samples (WI State of Laboratory of Hygiene Program). Leftover patient samples (n = 39) were used for an interlaboratory comparison of lead DBS. Lead DBS results were compared to whole blood methods. Results: The DBS ICP-MS methods using matrix-matched DBS calibrators had superior performance to the aqueous calibrations. There was a strong correlation between lead measured in DBS (matrix-matched) and whole blood for the three methods evaluated. Conclusion: Lead can be measured accurately by ICP-MS in DBS samples when matrix-matched calibrators are used. External quality control programs are valuable to assess the performance of DBS methods. DBS lead ICP-MS methods are a robust analytical option for lead screening even though the limitations of DBS are well recognized.

Abstract In malignant primary brain tumors, cancer cells infiltrate into the peritumoral brain structures which results in inevitable recurrence. Quantitative assessment of infiltrative heterogeneity in the peritumoral region, the area where biopsy or resection can be hazardous, is important for clinical decision making. Here, we derive a novel set of Artificial intelligence (AI)-based markers capturing the heterogeneity of tumor infiltration, by characterizing free water movement restriction in the peritumoral region using Diffusion Tensor Imaging (DTI)-based free water volume fraction maps. We leverage the differences in the peritumoral region of metastasis and glioblastomas, the former consisting of vasogenic versus the latter containing infiltrative edema, to extract a voxel-wise deep learning-based peritumoral microenvironment index (PMI). Descriptive characteristics of locoregional hubs of uniformly high PMI values are then extracted as AI-based markers to capture distinct aspects of infiltrative heterogeneity. The proposed markers are utilized to stratify patients’ survival and IDH1 mutation status on a population of 275 adult-type diffuse gliomas (CNS WHO grade 4). Our results show significant differences in the proposed markers between patients with different overall survival and IDH1 mutation status (t test, Wilcoxon rank sum test, linear regression; p

Background: As of July 2022, there have been more than 91.3 million cases of COVID-19 and nearly 1.03 million deaths in the United States alone. In addition, many people who survived COVID-19 had long-term symptoms, such as fatigue, dyspnea, loss of smell and taste, depression, and anxiety. Objectives: The purpose of our study is to evaluate the status of COVID-19 patients who were previously hospitalized. Methods: We conducted a single-center retrospective cohort study at Texas Tech University Health Sciences Center and its affiliated University Medical Center under IRB of L21-144. We included all patients hospitalized for COVID-19 and followed up in our Internal Medicine Clinic at any time between April 1, 2020, and April 1, 2021, and reviewed follow-up data for these patients after discharge. Results: A total of 128 patients were included; 59 (46%) were men, and 69 (54%) were women with an average age of 59.7 ± 14.8 years. Most of the patients (n = 78, 60.9%) identified their race as Hispanic or Latino origin; the next largest group was Caucasian (n = 29, 22.65%). The average number of days until post-hospitalization follow-up was 36 ± 38 days. The 50% of the patients (n = 64) used telemedicine for follow-up visits. Important comorbidities in these patients included diabetes (n = 84, 65.6%) and hypertension (n = 94, 73.4%). Thirty-four patients (26.6%) reported respiratory symptoms at their follow-up appointments, 24 patients (18.8%) reported constitutional symptoms, 12 patients (9.4%) reported GI symptoms, and 25 patients (19.5%) reported other symptoms, such as paresthesia, lower extremity edema, or psychological symptoms. After hospital discharge, 54 patients had follow-up chest x-rays, and 41 (75.9%) still had abnormal findings consistent with COVID-19 imaging characteristics. Follow-up laboratory tests identified 44 patients (77.2%, 57 tested) with elevated D-dimer levels, 44 patients (78.6%, 56 tested) with high ferritin levels, and 21patients (35.6%, 59 tested) with elevated troponin T HS levels. Conclusion: Long-lasting COVID-19 symptoms in these patients included respiratory symptoms (26.6%), constitutional symptoms (18.8%), GI symptoms (9.4%), and other symptoms, such as paresthesia, lower extremity edema, or psychological symptoms (19.5%). The rate of telehealth follow-up was 50%. Many patients had elevated inflammatory markers that will need follow up to determine the clinical implications.

Androstenedione (ASD) is a biomarker used in the diagnostic workup of hyperandrogenism, congenital adrenal hyperplasia, premature adrenarche, and polycystic ovary syndrome (PCOS). The Elecsys ASD competitive electrochemiluminescence immunoassay (Roche Diagnostics, Indianapolis, IN) is a new assay recently available in the US. Objective: This study evaluated the analytical and clinical performance of the Elecsys ASD assay. Design & Methods: We evaluated the linearity/analytical measuring range (AMR), precision, and accuracy of the Elecsys ASD assay on the cobas e601 analyzer. ASD was measured in serum/plasma in the Elecsys ASD, Immulite (Siemens Medical Solutions USA, Inc. Malvern, PA), and LC-MS/MS assays. Reference intervals (RI) were evaluated across genders, menopausal status, and in children. Statistical analysis was performed using EP evaluator and R program. Results: The Elecsys ASD assay had a linear response across the AMR. The intra- and inter-assay coefficients of variation at various concentrations were ≤4.5%. The Elecsys ASD assay had a mean difference of −0.04 ng/mL (−1.7%) with the LC-MS/MS assay, whereas the Immulite assay had a mean difference of 1.17 ng/mL (66%) and −1.22 ng/mL (−38%) compared to the LC-MS/MS and Elecsys ASD assays, respectively. The Roche recommended RIs for healthy men (0.280–1.52 ng/mL) and postmenopausal women (0.187–1.07 ng/mL) were successfully verified. The RIs for children were adopted from published data. For pre-menopausal women, a RI of

IntroductionThe lateral habenula (LHb) is an epithalamic nucleus associated with negative valence and affective disorders. It receives input via the stria medullaris (SM) and sends output via the fasciculus retroflexus (FR). Here, we use tractography to reconstruct and characterize this pathway.MethodsMulti-shell human diffusion magnetic resonance imaging (dMRI) data was obtained from the human connectome project (HCP) (n = 20, 10 males) and from healthy controls (n = 10, 6 males) scanned at our institution. We generated LHb afferents and efferents using probabilistic tractography by selecting the pallidum as the seed region and the ventral tegmental area as the output target.ResultsWe were able to reconstruct the intended streamlines in all individuals from the HCP dataset and our dataset. Our technique also aided in identification of the LHb. In right-handed individuals, the streamlines were significantly more numerous in the left hemisphere (mean ratio 1.59 ± 0.09, p = 0.04). In left-handed individuals, there was no hemispheric asymmetry on average (mean ratio 1.00 ± 0.09, p = 1.0). Additionally, these streamlines were significantly more numerous in females than in males (619.9 ± 159.7 vs. 225.9 ± 66.03, p = 0.04).ConclusionWe developed a method to reconstruct the SM and FR without manual identification of the LHb. This technique enables targeting of these fiber tracts as well as the LHb. Furthermore, we have demonstrated that there are sex and hemispheric differences in streamline number. These findings may have therapeutic implications and warrant further investigation.

OBJECTIVES/GOALS: The effect of immunosuppressive metabolites on anti-tumor immunity in human papillomavirus (HPV)-associated vs carcinogen-driven head and neck cancer is unknown. The objective of this study is to define the extent to which metabolites impair this response and identify novel metabolic targets for enhancing anti-tumor immunity. METHODS/STUDY POPULATION: HPV-associated and carcinogen-driven head and neck squamous cell carcinoma specimens were frozen following surgical excision, and tumor sections were cut onto glass slides. Slides were coated in alpha-cyano-4-hydroxy-cinnamic acid (CHCA) matrix and subjected to mass spectrometry imaging using matrix-assisted laser desorption ionization (MALDI) on a Bruker SolariX XR 12T Hybrid QqFT-ICR mass spectrometer run in positive mode. Slides were then stained for immunohistochemistry (IHC) using markers of CD8 T cells, macrophages (CD163), B cells (CD20), and tumor cells (panCK). Mass spectrometry imaging and IHC spatially resolved data will be co-registered and metabolite intensity in regions of interest (cell types) quantified. RESULTS/ANTICIPATED RESULTS: A total of seven HPV-associated (three metastatic lymph nodes and four primary tumors) and six carcinogen-driven (primary tumors) HNSC specimens were subjected to MALDI and IHC. Metabolites significantly enriched in HPV-associated HNSC relative to carcinogen-driven HNSC include 2,3-diphosphoglyceric acid, xanthine, 2,3,5-Trichloromaleylacetate, and indole-3-carboxyaldehyde. Metabolites significantly enriched in carcinogen-driven HNSC relative to HPV-associated HNSC include hesperetin 3'-O-sulfate, hypoxanthine, phosphorylcholine, and L-homocysteine sulfonic acid. In ongoing analyses, we anticipate identifying a relationship between CD8+ T cell enriched vs depleted regions and immunosuppressive metabolites (e.g., kynurenine, adenosine monophosphate). DISCUSSION/SIGNIFICANCE: Defining the extent to which CD8+ T cells interact with the metabolic milieu of the microenvironment will provide a foundation for metabolic Precision Medicine. Strategically targeting metabolic pathways to enhance the anti-tumor immune response will be leveraged for the design and implementation of immune modulatory metabolic therapy.

Vaccinations against COVID-19 infection have become a contentious issue in the United States. Multiple segments of society, including healthcare workers, have expressed concerns regarding the need for vaccination and the safety of current vaccines. Many hospital-based nurses have helped care for patients with severe COVID-19 infections. An anonymous online survey was sent to the nursing staff at University Medical Center in Lubbock, TX, USA, through a hospital-based email system to determine vaccination status and attitudes towards the COVID-19 vaccine and other routine vaccines. Multivariable regression analysis was used to determine factors associated with vaccination. A total of 251 nurses responded to this survey; 211 nurses (83.7%) had received the vaccine. Almost all nurses (242, 96%) had received all childhood vaccinations, and 231 (91.7%) had received an influenza vaccination in the prior year. A minority of nurses (75, 29.8%) supported mandatory vaccination for healthcare workers. The reasons for declining vaccination included the possibility that diet and alternative medications provided better protection against COVID-19. This survey demonstrates that over 80% of nurses working in a hospital managing very sick patients with COVID-19 infection had been vaccinated. However, nurses who did not take the annual influenza vaccine and did not consider other protective measures useful (such as mask-wearing) were significantly less likely to vaccinate. Nurses can provide an important resource for conversations with the public and patients about vaccine initiatives.

COIVD-19 vaccination of medical students is essential since these students will have contact with patients and will become future healthcare leaders. Hence, we surveyed medical students at Texas Tech University Health Science Center in Lubbock, TX, and received 234 responses. The majority of students were vaccinated against COVID-19 (215/234; 91.8%) and reported pro-vaccine attitudes, such as support for a COVID-19 booster shot (191/234; 81.6%) and an annual COVID-19 vaccine (186/234; 79.5%). Among those who did not receive the COVID-19 vaccine, the most frequent reasons included waiting for more evidence (16/19; 84.2%) and concern about the side effects (15/19; 79.0%). These results indicate that medical students consider vaccination important and suggest that students can provide an important resource for patients and public education.

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

Hyalinizing trabecular tumor (HTT), a rare low-malignant-potential thyroid neoplasm, is usually treated with conservative surgery. However, cytomorphological diagnosis of HTT is challenging due to the significant overlap of nuclear features with more common malignancies such as papillary thyroid carcinoma (PTC), which usually requires more radical surgical intervention. To avoid unnecessary overtreatment, a precise diagnosis of HTT is therefore essential. Advances in molecular diagnostics provide the opportunity to overcome the limitations of cytological analysis. We present a case of HTT in a 71-year-old male who was initially suspected to be PTC based on cytopathology. However, further molecular analysis revealed PAX8::GLIS3 gene fusion, classifying the lesion as HTT and preventing surgical overtreatment. We discuss the diagnostic pitfall of cytopathology in HTT and suggest using emerging molecular genetic tools to avoid it., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In patients with well-differentiated thyroid cancer, there is controversy about the prognostic importance of a large number of positive neck nodes and the potential value of radioiodine therapy. The purpose of this study was to evaluate this issue in the group of patients for whom it is most clinically important - those with classic histology and favorable T and M stage., Materials and Methods: Twenty-five patients met the following inclusion criteria: classic histology of papillary or follicular thyroid carcinoma treated with total thyroidectomy and neck dissection followed by adjuvant I-131 treatment in our department between January 1, 2003, and December 31, 2013; adult age of > 21 years; and American Joint Committee on Cancer (AJCC ) stage (8 th edition) of T0-3, N1b with ≥ 5 positive nodes, and M0., Results: The median positive node number was 10 (range, 5-31). The median adjuvant I-131 dose was 158 mCi (range, 150-219 mCi). The median follow-up in patients without recurrence after treatment was 7.3 years. The 10-year actuarial rates were favorable: overall survival, 100%; freedom from visible recurrence, 82%; and visible or biochemical recurrence, 72%., Conclusion: Recurrence was infrequent in our study population with ≥ 5 positive nodes following moderate-dose adjuvant I-131 treatment. These results are valuable in directing initial adjuvant therapy and follow-up intensity. Our results do not inform the question of the use of postoperative thyroglobulin (Tg) level to select N1b patients for low-dose I-131 treatment., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (© 2022 Greater Poland Cancer Centre.)