Genome-wide association and polygenic risk score estimation of type 2 diabetes mellitus in Kinh Vietnamese-A pilot study.

A genome-wide association study (GWAS) is a powerful tool in investigating genetic contribution, which is a crucial factor in the development of complex multifactorial diseases, such as type 2 diabetes mellitus. Type 2 diabetes mellitus is a major healthcare burden in the Western Pacific region; however, there is limited availability of genetic-associated data for type 2 diabetes in Southeast Asia, especially among the Kinh Vietnamese population. This lack of information exacerbates global healthcare disparities. In this study, 997 Kinh Vietnamese individuals (503 with type 2 diabetes and 494 controls) were prospectively recruited and their clinical and paraclinical information was recorded. DNA samples were collected and whole genome genotyping was performed. Standard quality control and genetic imputation using the 1000 Genomes database were executed. A polygenic risk score for type 2 diabetes was generated in different models using East Asian, European, and mix ancestry GWAS summary statistics as training datasets. After quality control and genetic imputation, 107 polymorphisms reached suggestive statistical significance for GWAS (≤5 × 10-6) and rs11079784 was one of the potential markers strongly associated with type 2 diabetes in the studied population. The best polygenic risk score model predicting type 2 diabetes mellitus had AUC = 0.70 (95% confidence interval = 0.62-0.77) based on a mix of ancestral GWAS summary statistics. These data show promising results for genetic association with a polygenic risk score estimation in the Kinh Vietnamese population; the results also highlight the essential role of population diversity in a GWAS of type 2 diabetes mellitus.

Modified Harborview Risk Score accurately predicts mortality for patients with ruptured abdominal aortic aneurysm.

OBJECTIVE: The modified Harborview Risk Score (HRS) is a simple measure initially derived from a single institutional dataset used to predict ruptured abdominal aortic aneurysm (rAAA) repair survival preoperatively using basic labs and vital signs collected upon presentation. However, validation of this widely applicable scoring system has not been performed. This study aims to validate this scoring system using a large multi-institutional database. METHODS: All patients who underwent repair of an rAAA from 2011 to 2018 in the National Surgical Quality Improvement Program (NSQIP) and at a single academic medical center were included. The modified HRS was calculated by assigning 1 point for each of the following: age >76 years, creatinine >2 mg/dL, international normalized ratio >1.8, and any systolic blood pressure less than 70 mmHg. Assessment of the prediction model was then completed. Using a primary outcome measure of 30-day mortality, the receiver operating characteristic area under the curve was calculated. The discrimination between datasets was compared using a Delong test. Mortality rates for each score were compared between datasets using the Pearson χ2 test. Comparative analysis for patients with a score of 4 was limited due to a small sample size. RESULTS: A total of 1536 patients were identified using NSQIP, and 163 patients were assessed in the institutional dataset. There were 518 patients with a score of 0 (455 NSQIP, 63 institutional), 676 patients with a score of 1 (617 NSQIP, 59 institutional), 391 patients with a score of 2 (364 NSQIP, 27 institutional), 106 with a score of 3 (93 NSQIP, 13 institutional), and 8 patients with a score of 4 (7 NSQIP, 1 institutional). No difference was found in the receiver operating characteristic area under the curves between datasets (P = .78). Thirty-day mortality was 10% NSQIP vs 22% institutional for a score of 0; 28% NSQIP vs 36% institutional for a score of 1; 41% NSQIP vs 44% institutional for a score of 2; 45% NSQIP vs 69% institutional for a score of 3; and 57% NSQIP vs 100% institutional for a score of 4. Score 0 was the only score with a significant mortality rate difference between datasets (P = .01). CONCLUSIONS: The modified HRS is confirmed to be broadly applicable as a clinical decision-making tool for patients presenting with rAAAs. Therefore, this easily applicable model should be applied for all patients presenting with rAAAs to assist with provider and patient decision-making prior to proceeding with repair.

Modified Harborview Risk Score improves ease in predicting mortality after ruptured abdominal aortic aneurysm repair.

OBJECTIVE: The Harborview Risk Score (HRS) is a simple, accurate 4-point preoperative risk scoring system used to predict 30-day mortality following ruptured abdominal aortic aneurysm (rAAA) repair. The HRS assigns 1 point for each of the following: age >76 years, pH <7.2, creatinine >2 mg/dL, and any episode of severe hypotension (systolic blood pressure <70 mmHg). One potential limitation of this risk scoring system is that arterial blood gas (ABG) analysis is required to determine arterial pH. Because ABG analysis is not routinely performed prior to patient transfer or rAAA repair, we sought to determine if the HRS could be modified by replacing pH with the international normalized ratio (INR), a factor that has been previously shown to have a strong and independent association with 30-day death after rAAA repair. METHODS: A retrospective review of all rAAA repairs done at a single academic medical center between January 2002 and December 2018 was performed. Our traditional HRS was compared with a modified score, in which pH <7.2 was replaced with INR >1.8. Patients were included if they underwent rAAA repair (open or endovascular), and if they had preoperative laboratory values available to calculate both the traditional and modified HRS. RESULTS: During the 17-year study period, 360 of 391 repairs met inclusion criteria. Observed 30-day mortality using the modified scoring system was 17% (18/106) for a score of 0 points, 43% (53/122) for 1 point, 54% (52/96) for 2 points, 84% (27/32) for 3 points, and 100% (4/4) for 4 points. Receiver operating characteristic analysis revealed similar ability of the two scoring systems to predict 30-day death: there was no significant difference in the area under the curve (AUC) comparing the traditional (AUC = 0.74) and modified (AUC = 0.72) HRS (P = .3). CONCLUSIONS: Although previously validated among a modern cohort of patients with rAAA, our traditional 4-point risk score is limited in real-world use by the need for an ABG. Substituting INR for pH improves the usefulness of our risk scoring system without compromising accuracy in predicting 30-day mortality after rAAA repair.

A comparison of alternative ranking methods in two-stage clinical trials with multiple interventions: An application to the anxiolysis for laceration repair in children trial.

BACKGROUND/AIMS: Multi-arm, multi-stage trials frequently include a standard care to which all interventions are compared. This may increase costs and hinders comparisons among the experimental arms. Furthermore, the standard care may not be evident, particularly when there is a large variation in standard practice. Thus, we aimed to develop an adaptive clinical trial that drops ineffective interventions following an interim analysis before selecting the best intervention at the final stage without requiring a standard care. METHODS: We used Bayesian methods to develop a multi-arm, two-stage adaptive trial and evaluated two different methods for ranking interventions, the probability that each intervention was optimal (Pbest) and using the surface under the cumulative ranking curve (SUCRA), at both the interim and final analysis. The proposed trial design determines the maximum sample size for each intervention using the Average Length Criteria. The interim analysis takes place at approximately half the pre-specified maximum sample size and aims to drop interventions for futility if either Pbest or the SUCRA is below a pre-specified threshold. The final analysis compares all remaining interventions at the maximum sample size to conclude superiority based on either Pbest or the SUCRA. The two ranking methods were compared across 12 scenarios that vary the number of interventions and the assumed differences between the interventions. The thresholds for futility and superiority were chosen to control type 1 error, and then the predictive power and expected sample size were evaluated across scenarios. A trial comparing three interventions that aim to reduce anxiety for children undergoing a laceration repair in the emergency department was then designed, known as the Anxiolysis for Laceration Repair in Children Trial (ALICE) trial. RESULTS: As the number of interventions increases, the SUCRA results in a higher predictive power compared with Pbest. Using Pbest results in a lower expected sample size when there is an effective intervention. Using the Average Length Criterion, the ALICE trial has a maximum sample size for each arm of 100 patients. This sample size results in a 86% and 85% predictive power using Pbest and the SUCRA, respectively. Thus, we chose Pbest as the ranking method for the ALICE trial. CONCLUSION: Bayesian ranking methods can be used in multi-arm, multi-stage trials with no clear control intervention. When more interventions are included, the SUCRA results in a higher power than Pbest. Future work should consider whether other ranking methods may also be relevant for clinical trial design.

Commutability and Uncertainty of Blood Hemoglobin A1c Testing Materials.

BACKGROUND: Hemoglobin A1C (HbA1C) is used to evaluate glycemic control over a three-month period. Blood matrix-based HbA1C materials are needed for quality control and evaluation of HbA1C measurements. This study investigated the commutability of blood materials (BMs) and aimed to upgrade BMs for HbA1C testing for use as proficiency test (PT) material. METHODS: We measured BMs from a DM blood donor (n = 1), an in vitro glycation procedure (n = 3), and from commercial sources (n = 2) for HbA1C in parallel with fresh unprocessed BMs (n = 3) and clinical blood samples (n = 25). Two NGSP-certified methods, including a turbidimetric and an enzymatic immunoassay, were used for HbA1C determinations. Commutability as investigated according to CLSI EP14-Ed4 guidelines. RESULTS: The commutable BMs exhibited a mean paired difference of 0% to 9% when compared to reference methods, whereas the non-commutable BMs represented a mean paired difference of 3% to 11%. Fresh, unprocessed BMs with a low HbA1C of 6.0% were more commutable than BMs with a high HbA1C. The values of HbA1C in BMs (mean and uncertainty following ISO Guide 35 for RM production) were applied to upgrade the PT material to be used as a reference material. The relative uncertainty of BM-Ndm-1 and BM-Gcb-3 were 1 and 0.4%, respectively. CONCLUSIONS: The commutability of hemoglobin in BMs is dependent on the preparation process. Blood materials with a high HbA1C content are usually less commutable versus materials with low HbA1C content when prepared by the same process. Our study showed BMs can be successfully used as quality control or PT materials.

Skin rejuvenation and photoaging protection using adipose-derived stem cell extracellular vesicles loaded with exogenous cargos.

BACKGROUND: Small extracellular vesicles from adipose-derived stem cells (ASC-sEVs) have gained remarkable attention for their regenerative and protective properties against skin aging. However, the use of ASC-sEVs to further encapsulate certain natural anti-aging compounds for synergistic effects has not been actively explored. For large-scale production in skincare industry, it is also crucial to standardize cost-effective methods to produce highly pure ASC-sEVs. METHODS: Human ASCs were expanded in serum-free media with different compositions to first optimize the sEV production. ASC-sEVs from different batches were then purified using tangential flow filtration and sucrose cushion ultracentrifugation, followed by extensive characterization for identity and content profiling including proteomics, lipidomics and miRNA sequencing. ASC-sEVs were further loaded with nicotinamide riboside (NR) and resveratrol by sonication-incubation method. The therapeutic effect of ASC-sEVs and loaded ASC-sEVs was tested on human keratinocyte cell line HaCaT exposed to UVB by measuring reactive oxygen species (ROS). The loaded ASC-sEVs were later applied on the hand skin of three volunteers once a day for 8 weeks and skin analysis was performed every 2 weeks. RESULTS: Our standardized workflow produced ASC-sEVs with high yield, high purity and with stable characteristics and consistent biocargo among different batches. The most abundant subpopulations in ASC-sEVs were CD63+ (∼30%) and CD81+ -CD63+ (∼35%). Purified ASC-sEVs could be loaded with NR and resveratrol at the optimized loading efficiency of ∼20%. In UVB-exposed HaCaT cells, loaded ASC-sEVs could reduce ROS by 38.3%, higher than the sEVs (13.3%) or compounds (18.5%) individually. In human trial, application of loaded ASC-sEVs after 8 weeks substantially improved skin texture, increased skin hydration and elasticity by 104% and reduced mean pore volume by 51%. CONCLUSIONS: This study demonstrated a robust protocol to produce ASC-sEVs and exogenously load them with natural compounds. The loaded ASC-sEVs exhibited synergistic effects of both sEVs and anti-aging compounds in photoaging protection and skin rejuvenation.

Pharmacologic Procedural Distress Management During Laceration Repair in Children: A Systematic Review.

OBJECTIVES: To systematically appraise the literature on the relative effectiveness of pharmacologic procedural distress management agents for children undergoing laceration repair. METHODS: Six databases were searched in August 2021, and the search was updated in January 2023. We included completed randomized or quasi-randomized trials involving ( a ) children younger than 15 years undergoing laceration repair in the emergency department; ( b ) randomization to at least one anxiolytic, sedative, and/or analgesic agent versus any comparator agent or placebo; ( c ) efficacy of procedural distress management measured on any scale. Secondary outcomes were pain during the procedure, administration acceptance, sedation duration, additional sedation, length of stay, and stakeholder satisfaction. Cochrane Collaboration's risk-of-bias tool assessed individual studies. Ranges and proportions summarized results where applicable. RESULTS: Among 21 trials (n = 1621 participants), the most commonly studied anxiolytic agents were midazolam, ketamine, and N 2 O. Oral midazolam, oral ketamine, and N 2 O were found to reduce procedural distress more effectively than their comparators in 4, 3, and 2 studies, respectively. Eight studies comparing routes, doses, or volumes of administration of the same agent led to indeterminate results. Meta-analysis was not performed because of heterogeneity in comparators, routes, and outcome measures across studies. CONCLUSIONS: Based on procedural distress reduction, this study favors oral midazolam and oral ketamine. However, this finding should be interpreted with caution because of heterogeneous comparators across studies and minor conflicting results. An optimal agent for procedural distress management cannot be recommended based on the limited evidence. Future research should seek to identify the minimal, essential measures of patient distress during pharmacologic anxiolysis and/or sedation in laceration repair to guide future trials and reviews.

Time-course cross-species transcriptomics reveals conserved hepatotoxicity pathways induced by repeated administration of cyclosporine A.

Cyclosporine A (CsA) has shown efficacy against immunity-related diseases despite its toxicity in various organs, including the liver, emphasizing the need to elucidate its underlying hepatotoxicity mechanism. This study aimed to capture the alterations in genome-wide expression over time and the subsequent perturbations of corresponding pathways across species. Six data from humans, mice, and rats, including animal liver tissue, human liver microtissues, and two liver cell lines exposed to CsA toxic dose, were used. The microtissue exposed to CsA for 10 d was analyzed to obtain dynamically differentially expressed genes (DEGs). Single-time points data at 1, 3, 5, 7, and 28 d of different species were used to provide additional evidence. Using liver microtissue-based longitudinal design, DEGs that were consistently up- or down-regulated over time were captured, and the well-known mechanism involved in CsA toxicity was elucidated. Thirty DEGs that consistently changed in longitudinal data were also altered in 28-d rat in-house data with concordant expression. Some genes (e.g. TUBB2A, PLIN2, APOB) showed good concordance with identified DEGs in 1-d and 7-d mouse data. Pathway analysis revealed up-regulations of protein processing, asparagine N-linked glycosylation, and cargo concentration in the endoplasmic reticulum. Furthermore, the down-regulations of pathways related to biological oxidations and metabolite and lipid metabolism were elucidated. These pathways were also enriched in single-time-point data and conserved across species, implying their biological significance and generalizability. Overall, the human organoids-based longitudinal design coupled with cross-species validation provides temporal molecular change tracking, aiding mechanistic elucidation and biologically relevant biomarker discovery.

Point of care blood glucose devices in the hospital setting.

Dysglycemia is common among hospitalized patients. Accurate point-of-care (POC) glucose monitoring is necessary for the safe administration of insulin. Unfortunately, POC glucose meters are not all created equal. Interfering factors such as abnormal hematocrit, abnormal oxygen tension, and oxidizing/reducing substances can lead to inaccurate glucose measurements and result in inappropriate insulin dosing. The introduction of autocorrecting glucose meters has changed the POC testing landscape. Autocorrecting glucose meters provide more accurate measurements and have been associated with improved glycemic control in hospitalized patients. Continuous glucose monitoring has also created interest in using these platforms in at-risk inpatient populations. Future glucose monitoring technologies such as artificial intelligence/machine learning, wearable smart devices, and closed-loop insulin management systems are poised to transform glycemic management. The goal of this review is to provide an overview of glucose monitoring technology, summarize the clinical impact of glucose monitoring accuracy, and highlight emerging and future POC glucose monitoring technologies.

Machine learning and artificial intelligence for the diagnosis of infectious diseases in immunocompromised patients.

PURPOSE OF REVIEW: Immunocompromised patients are at high risk for infection. During the coronavirus disease (COVID-19) pandemic, immunocompromised patients exhibited increased odds of intensive care unit admission and death. Early pathogen identification is essential to mitigating infection related risk in immunocompromised patients. Artificial intelligence (AI) and machine learning (ML) have tremendous appeal to address unmet diagnostic needs. These AI/ML tools often rely on the wealth of data found in healthcare to enhance our ability to identify clinically significant patterns of disease. To this end, our review provides an overview of the current AI/ML landscape as it applies to infectious disease testing with emphasis on immunocompromised patients. RECENT FINDINGS: Examples include AI/ML for predicting sepsis in high risk burn patients. Likewise, ML is utilized to analyze complex host-response proteomic data to predict respiratory infections including COVID-19. These same approaches have also been applied for pathogen identification of bacteria, viruses, and hard to detect fungal microbes. Future uses of AI/ML may include integration of predictive analytics in point-of-care (POC) testing and data fusion applications. SUMMARY: Immunocompromised patients are at high risk for infections. AI/ML is transforming infectious disease testing and has great potential to address challenges encountered in the immune compromised population.

Human-induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation.

STUDY QUESTION: Can in vitro maturation (IVM) and developmental competence of human oocytes be improved by co-culture with ovarian support cells (OSCs) derived from human-induced pluripotent stem cells (hiPSCs)? SUMMARY ANSWER: OSC-IVM significantly improves the rates of metaphase II (MII) formation and euploid Day 5 or 6 blastocyst formation, when compared to a commercially available IVM system. WHAT IS KNOWN ALREADY: IVM has historically shown highly variable performance in maturing oocytes and generating oocytes with strong developmental capacity, while limited studies have shown a positive benefit of primary granulosa cell co-culture for IVM. We recently reported the development of OSCs generated from hiPSCs that recapitulate dynamic ovarian function in vitro. STUDY DESIGN, SIZE, DURATION: The study was designed as a basic science study, using randomized sibling oocyte specimen allocation. Using pilot study data, a prospective sample size of 20 donors or at least 65 oocytes per condition were used for subsequent experiments. A total of 67 oocyte donors were recruited to undergo abbreviated gonadotropin stimulation with or without hCG triggers and retrieved cumulus-oocyte complexes (COCs) were allocated between the OSC-IVM or control conditions (fetal-like OSC (FOSC)-IVM or media-only IVM) in three independent experimental design formats. The total study duration was 1 April 2022 to 1 July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Oocyte donors between the ages of 19 and 37 years were recruited for retrieval after informed consent, with assessment of anti-Mullerian hormone, antral follicle count, age, BMI and ovarian pathology used for inclusion and exclusion criteria. In experiment 1, 27 oocyte donors were recruited, in experiment 2, 23 oocyte donors were recruited, and in experiment 3, 17 oocyte donors and 3 sperm donors were recruited. The OSC-IVM culture condition was composed of 100 000 OSCs in suspension culture with hCG, recombinant FSH, androstenedione, and doxycycline supplementation. IVM controls lacked OSCs and contained either the same supplementation, FSH and hCG only (a commercial IVM control), or FOSCs with the same supplementation (Media control). Experiment 1 compared OSC-IVM, FOSC-IVM, and a Media control, while experiments 2 and 3 compared OSC-IVM and a commercial IVM control. Primary endpoints in the first two experiments were the MII formation (i.e. maturation) rate and morphological quality assessment. In the third experiment, the fertilization and embryo formation rates were assessed with genetic testing for aneuploidy and epigenetic quality in blastocysts. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a statistically significant improvement (∼1.5×) in maturation outcomes for oocytes that underwent IVM with OSCs compared to control Media-IVM and FOSC-IVM in experiment 1. More specifically, the OSC-IVM group yielded a MII formation rate of 68% ± 6.83% SEM versus 46% ± 8.51% SEM in the Media control (P = 0.02592, unpaired t-test). FOSC-IVM yielded a 51% ± 9.23% SEM MII formation rate which did not significantly differ from the media control (P = 0.77 unpaired t-test). Additionally, OSC-IVM yielded a statistically significant ∼1.6× higher average MII formation rate at 68% ± 6.74% when compared to 43% ± 7.90% in the commercially available IVM control condition (P = 0.0349, paired t-test) in experiment 2. Oocyte morphological quality between OSC-IVM and the controls did not significantly differ. In experiment 3, OSC-IVM oocytes demonstrated a statistically significant improvement in Day 5 or 6 euploid blastocyst formation per COC compared to the commercial IVM control (25% ± 7.47% vs 11% ± 3.82%, P = 0.0349 logistic regression). Also in experiment 3, the OSC-treated oocytes generated blastocysts with similar global and germline differentially methylated region epigenetic profiles compared commercial IVM controls or blastocysts after either conventional ovarian stimulation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: While the findings of this study are compelling, the cohort size remains limited and was powered on preliminary pilot studies, and the basic research nature of the study limits generalizability compared to randomized control trials. Additionally, use of hCG-triggered cycles results in a heterogenous oocyte cohort, and potential differences in the underlying maturation state of oocytes pre-IVM may limit or bias findings. Further research is needed to clarify and characterize the precise mechanism of action of the OSC-IVM system. Further research is also needed to establish whether these embryos are capable of implantation and further development, a key indication of their clinical utility. WIDER IMPLICATIONS OF THE FINDINGS: Together, these findings demonstrate a novel approach to IVM with broad applicability to modern ART practice. The controls used in this study are in line with and have produced similar to findings to those in the literature, and the outcome of this study supports findings from previous co-culture studies that found benefits of primary granulosa cells on IVM outcomes. The OSC-IVM system shows promise as a highly flexible IVM approach that can complement a broad range of stimulation styles and patient populations. Particularly for patients who cannot or prefer not to undergo conventional gonadotropin stimulation, OSC-IVM may present a viable path for obtaining developmentally competent, mature oocytes. STUDY FUNDING/COMPETING INTEREST(S): A.D.N., A.B.F., A.G., B.P., C.A., C.C.K., F.B., G.R., K.S.P., K.W., M.M., P.C., S.P., and M.-J.F.-G. are shareholders in the for-profit biotechnology company Gameto Inc. P.R.J.F. declares paid consultancy for Gameto Inc. P.C. also declares paid consultancy for the Scientific Advisory Board for Gameto Inc. D.H.M. has received consulting services from Granata Bio, Sanford Fertility and Reproductive Medicine, Gameto, and Buffalo IVF, and travel support from the Upper Egypt Assisted Reproduction Society. C.C.K., S.P., M.M., A.G., B.P., K.S.P., G.R., and A.D.N. are listed on a patent covering the use of OSCs for IVM: U.S. Provisional Patent Application No. 63/492,210. Additionally, C.C.K. and K.W. are listed on three patents covering the use of OSCs for IVM: U.S. Patent Application No. 17/846,725, U.S Patent Application No. 17/846,845, and International Patent Application No.: PCT/US2023/026012. C.C.K., M.P.S., and P.C. additionally are listed on three patents for the transcription factor-directed production of granulosa-like cells from stem cells: International Patent Application No.: PCT/US2023/065140, U.S. Provisional Application No. 63/326,640, and U.S. Provisional Application No. 63/444,108. The remaining authors have no conflicts of interest to declare.

Risk factors for HIV infection at a large urban emergency department: a cross-sectional study.

OBJECTIVES: In 2019, the US Preventative Services Task Force released updated guidelines recommending HIV screening in all individuals aged 15-64 years and all pregnant females. In the current study, we aimed to identify risk factors for HIV infection in an emergency department (ED) population. METHODS: We performed a cross-sectional study that employed a post hoc risk factor analysis of ED patients ≥18 years who were screened for HIV between 27 November 2018 and 26 November 2019, at a single urban, quaternary referral academic hospital. Patients were screened using HIV antigen/antibody testing and diagnoses were confirmed using HIV-1/HIV-2 antibody testing. The outcome of interest was the number of positive HIV tests. Multiple logistic regression models were used to identify risk factors associated with HIV positivity. RESULTS: 14 335 adult patients were screened for HIV (mean age: 43±14 years; 52% female). HIV seroprevalence was 0.7%. Independent risk factors for HIV positivity included male sex (adjusted OR (aOR) 3.1 (95% CI 1.7 to 5.6)), unhoused status (aOR 2.9 (95% CI 1.7 to 4.9)), history of illicit drug use (aOR 1.8 (95% CI 1.04 to 3.13)) and Medicare insurance status (aOR 2.2 (95% CI 1.1 to 4.4)). CONCLUSIONS: The study ED services a high-risk population with regard to HIV infection. These data support universal screening of ED patients for HIV. Risk factor profiles could improve targeted screening at institutions without universal HIV testing protocols.

Atomistic Wear Mechanisms in Diamond: Effects of Surface Orientation, Stress, and Interaction with Adsorbed Molecules.

Despite its unrivaled hardness, diamond can be severely worn during the interaction with others, even softer materials. In this work, we calculate from first-principles the energy and forces necessary to induce the atomistic wear of diamond and compare them for different surface orientations and passivation by oxygen, hydrogen, and water fragments. The primary mechanism of wear is identified as the detachment of the carbon chains. This is particularly true for oxidized diamond and diamonds interacting with silica. A very interesting result concerns the role of stress, which reveals that compressive stresses can highly favor wear, making it even energetically favorable.

Development of a "Geo-Tagged" tumor sample registry: intra-operative linkage of sample location to imaging.

PURPOSE: There is a growing body of literature documenting glioma heterogeneity in terms of radiographic, histologic, molecular, and genetic characteristics. Incomplete spatial specification of intraoperative tumor samples may contribute to variability in the results of pathological and biological investigations. We have developed a system, termed geo-tagging, for routine intraoperative linkage of each tumor sample to its location via neuronavigation. METHODS: This is a single-institution, IRB approved, prospective database of undergoing clinically indicated surgery. We evaluated relevant factors affecting data collection by this registry, including tumor and surgical factors (e.g. tumor volume, location, grade and surgeon). RESULTS: Over a 2-year period, 487 patients underwent craniotomy for an intra-axial tumor. Of those, 214 underwent surgery for a newly diagnosed or recurrent glioma. There was significant variation in the average number of samples collected per registered case, with a range of samples from 2.53 to 4.75 per tumor type. Histology and grade impacted on sampling with a range of 2.0 samples per tumor in Grade four, IDH-WT gliomas to 4.5 samples in grade four, IDH-mutant gliomas. The range of cases with sampling per surgeon was 6 to 99 with a mean of 47.6 cases and there was a statistically significant differences between surgeons. Tumor grade did not have a statistically significant impact on number of samples per case. No significant correlation was found between the number of samples collected and enhancing tumor volume, EOR, or volume of tumor resected. CONCLUSION: We are using the results of this analysis to develop a prospective sample collection protocol.

Dynamic Imaging is the Ideal Modality for the Diagnosis of Popliteal Artery Entrapment Syndrome.

BACKGROUND: Popliteal Artery Entrapment Syndrome (PAES) is a rare vascular condition with significant equipoise on how to properly diagnose and evaluate relevant imaging. This can lead to misdiagnosis and delay in surgical management. The objective of this study is to describe and compare distinct imaging features of dynamic versus static images to help determine the ideal imaging modality for diagnosis of PAES. METHODS: This is a retrospective review of patients referred for PAES at a single institution. We reviewed noninvasive imaging studies, diagnostic arteriograms, and cross-sectional images which include computed tomography angiography (CTA) or magnetic resonance angiography (MRA). For each affected and unaffected extremity, the characteristic collaterals for PAES were named and measured on arteriogram using Picture Archiving and Communication Software. Available cross-sectional images were also analyzed and compared with arteriogram and intraoperative findings during surgical exploration. RESULTS: There were 23 patients referred for PAES who underwent diagnostic evaluation and surgical management between 2013 and 2022. All patients had a duplex ultrasound that revealed a mean popliteal peak systolic velocity of 78 cm/sec at rest. With forced plantar flexion, the peak systolic velocity increased to a mean 175 cm/sec. A total of 12 extremities had complete loss of flow with provocation during duplex ultrasound. All patients underwent diagnostic angiography of 46 extremities. All limbs with PAES (n = 35) exhibited complete popliteal artery occlusion during angiography with forced plantar flexion. Distinct angiographic findings on resting images included a well-developed medial sural artery in 100% of limbs with PAES with a mean diameter of 2.7 mm. In limbs without PAES, only 80% had a visualized medial sural artery on arteriogram with a mean diameter of 2.0 mm (P = 0.1). A lateral sural artery was seen in 85% of affected extremities (mean diameter of 1.8 mm), while an anterior tibial recurrent artery was seen in 59% of affected extremities (mean diameter of 1.3 mm). In unaffected limbs, there were no visible lateral sural or anterior tibial recurrent arteries. The mean contrast used with diagnostic arteriograms was 58 milliliters (range 10-100 milliliters). Axial imaging was available for 9 affected extremities. Five had a previous MRA with only 1 being truly positive for arterial compression. Four extremities had previous CTA with 3 being falsely negative despite having type 3 PAES discovered during surgical exploration. CONCLUSIONS: Dynamic imaging with angiography provides immediate surgeon feedback by visualizing popliteal artery compression and enlarged sural collaterals during resting arteriography. The medial sural collateral is enlarged in patients with PAES and often the lateral sural and anterior tibial recurrent arteries can be visualized as well. CTA and MRA are associated with high false-negative rates, and therefore cause delays in diagnosis and surgical management of PAES. Dynamic imaging should, therefore, be the gold standard for the diagnosis of PAES.

Evaluation of pharmacist guided intervention using procalcitonin and respiratory virus testing.

INTRODUCTION: Acute respiratory infections make up a sizable percentage of emergency department (ED) visits and many result in antibiotics being prescribed. Procalcitonin (PCT) has been found to reduce antibiotic use in both outpatient and critical care settings, yet remains underused in the ED. This study aimed to evaluate whether point of care molecular influenza and Respiratory Syncytial Virus (RSV) testing, PCT, and a pharmacist driven educational intervention in aggregate optimizes antibiotic and antiviral prescribing in the ED setting. METHODS: A randomized trial of the Cobas Liat Flu/RSV Assay, procalcitonin, and the use of pharmacist-led education in patients 0-50 years of age being seen in the ED for Influenza Like Illness (ILI) or acute respiratory illness. The study enrolled 200 ED patients between March 2018 and April 2022. RESULTS: There was little difference in antibiotic or antiviral prescribing between the intervention and control groups in this study (39%-32% = 7.0%, 95% CI: -6.2, 20.2, P = 0.30). However, a post-hoc analysis of the use of procalcitonin showed results were used as indicated in the ED (P = 0.001). CONCLUSION: PCT can be used in both adult and pediatric populations to help guide the decision of whether to treat with antibiotics in the ED setting. Pharmacist guided education may not be a driving factor.

Evaluation of Commercially Available High-Throughput SARS-CoV-2 Serologic Assays for Serosurveillance and Related Applications.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys can estimate cumulative incidence for monitoring epidemics, requiring assessment of serologic assays to inform testing algorithm development and interpretation of results. We conducted a multilaboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serologic assays using blinded panels of 1,000 highly characterized specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%), and precision (intraclass correlation coefficient 0.55-0.99). Durability of antibody detection was dependent on antigen and immunoglobulin targets; antispike and total Ig assays demonstrated more stable longitudinal reactivity than antinucleocapsid and IgG assays. Assays with high sensitivity, specificity, and durable antibody detection are ideal for serosurveillance, but assays demonstrating waning reactivity are appropriate for other applications, including correlation with neutralizing activity and detection of anamnestic boosting by reinfections. Assay performance must be evaluated in context of intended use, particularly in the context of widespread vaccination and circulation of SARS-CoV-2 variants.

Risk factors for hepatitis C virus infection at a large urban emergency department.

In 2020, Centers for Disease Control and Prevention (CDC) released guidelines recommending HCV screening in all adults 18 years and older. In the current study, we aimed to identify risk factors for HCV infection in an ED population. We performed a retrospective analysis of ED patients ≥ 18 years who were screened for HCV between 28 November 2018, and 27 November 2019, at a single urban, quaternary referral academic hospital. An HCV-antibody immunoassay (HCV-Ab) was used for screening; positive results were confirmed by measuring HCV ribonucleic acid (RNA). The outcome of interest was the number of new HCV diagnoses (presence of viremia by HCV RNA testing). Multiple logistic regression models were used to identify risk factors associated with a new HCV diagnosis. 16,722 adult patients were screened for HCV (mean age: 46 ± 15 years; 51% female). HCV seroprevalence was 5%. Independent risk factors for HCV included increasing age [10-year aOR 1.26 (95% CI 1.23, 1.30)], male sex [aOR 1.25 (95% CI 1.03, 1.51)], undomiciled housing status [aOR 2.8 (95% CI 2.3, 3.5)], history of tobacco use [aOR 3.0 (95% CI 2.3, 3.9)], history of illicit drug use [aOR 3.6 (95% CI 2.9, 4.5)], Medicaid insurance status [aOR 4.0 (95% CI 2.9, 5.5)] and Medicare insurance status [aOR 1.6 (95% CI 1.1, 2.2)].The ED services a high-risk population with regards to HCV infection. These data support universal screening of ED patients for HCV. Risk factor profiles could improve targeted screening at institutions without universal testing protocols.

Risk Factors for Syphilis at a Large Urban Emergency Department.

BACKGROUND: The prevalence of syphilis is increasing in the United States. The emergency department (ED) is an important setting to screen and treat underserved populations. To tailor testing protocols to the local population, we aimed to identify risk factors for syphilis positivity in ED patients. METHODS: We performed a retrospective analysis of ED patients who were screened for syphilis between November 2018 and August 2020. Patients were screened for Treponema pallidum antibody using a multiplex flow immunoassay, and positive results were confirmed by rapid plasma reagin or T. pallidum particle agglutination. Risk factors for new syphilis diagnoses were identified using multiple logistic regression. RESULTS: We screened 1974 patients for syphilis (mean age, 37 ± 16 years; 56% female). We identified 201 patients with new infections without previous treatment. Independent risk factors for a new diagnosis of syphilis included housing status (undomiciled, 23% [60 of 256]; domiciled, 9% [133 of 1559]; adjusted odds ratio [aOR], 1.9 [95% confidence interval {CI}, 1.2-3.0]), history of HIV (positive, 44% [28 of 63]; negative, 9% [173 of 1893]; aOR, 5.8 [95% CI, 3.0-11.2]), tobacco use (positive, 15% [117 of 797]; negative, 4% [29 of 665]; aOR, 2.4 [95% CI, 1.5-3.9]), and illicit drug use (positive, 14% [112 of 812]; negative, 8% [52 of 678]; aOR, 2.2 [95% CI, 1.0-2.5]). CONCLUSIONS: Undomiciled housing status, history of HIV, history of tobacco use, and history of illicit drug use were independently associated with a new diagnosis of syphilis in the ED. Broadening targeted syphilis screening algorithms beyond sexually transmitted disease-related complaints could help identify new syphilis cases for treatment.

Patient satisfaction and cost savings analysis of the telemedicine program within a neuro-oncology department.

PURPOSE: Unique challenges exist in the utilization of telemedicine for neurological and surgical specialties. We examined the differences in patient satisfaction for telemedicine versus in-person visits within a Neuro-Oncology Program to assess whether there was a difference between surgical and medical specialties. We also examined the potential cost savings benefits of utilizing telemedicine. METHODS: 1189 Press Ganey surveys in the Department of Neuro-Oncology (982 in-person and 207 telemedicine) by surgical and medical neuro-oncology patients between 04/01/2020 and 06/30/2021 were reviewed. Survey results were divided into 4 categories (Access, Provider, Technology (telemedicine only), and Overall Satisfaction). Results were analyzed for the impact of telemedicine versus in-person visits, and gender, age, insurance, and specialty. Cost savings were calculated based on potential travel distance and lost productivity. RESULTS: Survey results from telemedicine visits demonstrated that patients with private insurance returned higher scores in the Provider (p = 0.0089), Technology (p = 0.00187), and Overall (p = 0.00382) categories. Surgical patients returned higher scores for Access (p = 0.0015), Technology (p = 0.0002), and Overall (p = 0.0019). When comparing telemedicine to in-person scores, in-person scored higher in Provider (p = 0.0092) for all patients, while in-person scored higher in Access (p = 0.0252) amongst surgical patients. Cost analysis revealed that telemedicine allowed patients to save an average of 4.1 to 5.6 h per visit time and a potential cost savings of up to $223.3 ± 171.4. CONCLUSION: Telemedicine yields equivalent patient satisfaction when employed in surgical as compared to medical Neuro-Oncology patients with the potential to lessen the financial and time burden on neuro-oncology patients.