Childhood Maltreatment and Physical Health in College Students: Physical Activity and Binge Eating as Moderators.

Child maltreatment leads to pervasive physical health problems. For individuals with a child maltreatment history, physiological risk factors for future disease are apparent by young adulthood. The current study explored the role that physical activity and binge eating may have in the trajectory from child maltreatment to poor adult health. We administered the following measures to 100 female and male college students: resting heart rate assessment, symptoms of illness, and the Childhood Trauma Questionnaire (CTQ-SF) to assess maltreatment history. After this session, participants wore a Fitbit that provided physical activity data (low, moderate, and vigorous activity, and total steps) in a free-living environment for a period of 10 days. Physical activity moderated the pathway between maltreatment history and both resting heart rate and symptoms of illness. In individuals with higher CTQ scores, more low-intensity physical activity and total steps were related to fewer symptoms of illness and lower resting heart rate, respectively. Binge-eating behavior moderated the pathway between maltreatment and symptoms of illness, such that greater binge-eating behavior was associated with more self-reported illness symptoms in participants with higher CTQ scores. These findings suggest that on-campus interventions targeting physical activity and healthy eating behaviors will improve the long-term health of young adults with maltreatment history.

Cerebral angiography in outpatient endovascular centers: roadmap and lessons learned from interventional radiology, cardiology, and vascular surgery.

A growing proportion of percutaneous procedures are performed in outpatient centers. The shift from hospitals to ambulatory surgery centers and office-based laboratories has been driven by a number of factors, including declining reimbursements, increased patient demand, and competition for hospital resources. This transition has been dominated by the interventional radiology, cardiology, and vascular surgery fields. Cerebral angiography, in contrast, is still performed almost exclusively in a hospital-based setting, despite sharing many features with other endovascular procedures commonly performed in outpatient centers. As interest grows in performing cerebral angiography in outpatient endovascular centers, much can be learned from the decades of experience that our interventional colleagues have in the outpatient setting. In this article we examine the outpatient experience of other interventional fields and apply key principles to evaluate the prospect of outpatient neurointervention. The literature suggests that cerebral angiography can feasibly be performed in an outpatient center in both private and academic settings, as some groups have begun to do. Outpatient endovascular centers have helped to improve the patient experience, liberate inpatient resources, and control costs in other interventional fields, and might offer neurointerventionalists an opportunity to do the same.

A critical assessment of using ChatGPT for extracting structured data from clinical notes.

Existing natural language processing (NLP) methods to convert free-text clinical notes into structured data often require problem-specific annotations and model training. This study aims to evaluate ChatGPT's capacity to extract information from free-text medical notes efficiently and comprehensively. We developed a large language model (LLM)-based workflow, utilizing systems engineering methodology and spiral "prompt engineering" process, leveraging OpenAI's API for batch querying ChatGPT. We evaluated the effectiveness of this method using a dataset of more than 1000 lung cancer pathology reports and a dataset of 191 pediatric osteosarcoma pathology reports, comparing the ChatGPT-3.5 (gpt-3.5-turbo-16k) outputs with expert-curated structured data. ChatGPT-3.5 demonstrated the ability to extract pathological classifications with an overall accuracy of 89%, in lung cancer dataset, outperforming the performance of two traditional NLP methods. The performance is influenced by the design of the instructive prompt. Our case analysis shows that most misclassifications were due to the lack of highly specialized pathology terminology, and erroneous interpretation of TNM staging rules. Reproducibility shows the relatively stable performance of ChatGPT-3.5 over time. In pediatric osteosarcoma dataset, ChatGPT-3.5 accurately classified both grades and margin status with accuracy of 98.6% and 100% respectively. Our study shows the feasibility of using ChatGPT to process large volumes of clinical notes for structured information extraction without requiring extensive task-specific human annotation and model training. The results underscore the potential role of LLMs in transforming unstructured healthcare data into structured formats, thereby supporting research and aiding clinical decision-making.

AZGP1 deficiency promotes angiogenesis in prostate cancer.

BACKGROUND: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. METHOD: AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples. RESULT: Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1-/- mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues. CONCLUSION: AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.

Partnership in Cancer Research (PCAR) Program Increases Medical Student Knowledge and Confidence to Perform Cancer Research.

Arkansas has a high cancer burden, and a pressing need exists for more medical students to pursue oncology as a career. The Partnership in Cancer Research (PCAR) program provides a summer research experience at the University of Arkansas for Medical Sciences for 12 medical students who have completed their first year of medical training. A majority of participants spend time pursuing cancer research in basic science, clinical, or community-based research. Students report on their research progress in an interactive "Live from the Lab!" series and assemble a final poster presentation describing their findings. Other activities include participation in a moderated, cancer-patient support group online, lecture series on cancer topics, medical simulations, palliative care clinic visit, "Death Over Dinner" event, and an entrepreneurship competition. Students completed surveys over PCAR's first 2 years in operation to evaluate all aspects of the program. Surveys reveal that students enthusiastically embraced the program in its entirety. This was especially true of the medical simulations which received the highest evaluations. Most significantly, surveys revealed that the program increased cancer knowledge and participant confidence to perform cancer research.

The VEBAS score: a practical scoring system for intracranial dural arteriovenous fistula obliteration.

BACKGROUND: Tools predicting intracranial dural arteriovenous fistulas (dAVFs) treatment outcomes remain scarce. This study aimed to use a multicenter database comprising more than 1000 dAVFs to develop a practical scoring system that predicts treatment outcomes. METHODS: Patients with angiographically confirmed dAVFs who underwent treatment within the Consortium for Dural Arteriovenous Fistula Outcomes Research-participating institutions were retrospectively reviewed. A subset comprising 80% of patients was randomly selected as training dataset, and the remaining 20% was used for validation. Univariable predictors of complete dAVF obliteration were entered into a stepwise multivariable regression model. The components of the proposed score (VEBAS) were weighted based on their ORs. Model performance was assessed using receiver operating curves (ROC) and areas under the ROC. RESULTS: A total of 880 dAVF patients were included. Venous stenosis (presence vs absence), elderly age (<75 vs ≥75 years), Borden classification (I vs II-III), arterial feeders (single vs multiple), and past cranial surgery (presence vs absence) were independent predictors of obliteration and used to derive the VEBAS score. A significant increase in the likelihood of complete obliteration (OR=1.37 (1.27-1.48)) with each additional point in the overall patient score (range 0-12) was demonstrated. Within the validation dataset, the predicted probability of complete dAVF obliteration increased from 0% with a 0-3 score to 72-89% for patients scoring ≥8. CONCLUSION: The VEBAS score is a practical grading system that can guide patient counseling when considering dAVF intervention by predicting the likelihood of treatment success, with higher scores portending a greater likelihood of complete obliteration.

Organic matter biofiltration performance modeling: Influence of influent water quality, operating conditions, and biomass.

The impact of source water dissolved organic matter (DOM) origin, empty bed contact time (EBCT), temperature, and pretreatment methods on biofiltration performance was evaluated and predictive models based on experimental data were developed. Three DOM source water types, terrestrial, microbial, and treated wastewater (WW) effluent, were utilized. A model was developed to predict biofilter performance for dissolved organic carbon (DOC) removal based on the influent biodegradable DOC (BDOC) fraction, a single active biomass measurement from the top of the filter and the filter EBCT. A biomass distribution model was developed to predict total active biomass throughout the filter based on a single biomass measurement from the top of the filter. The measured BDOC fractions were 21 % for the nonWW impacted source waters, 36 % for the WW effluents and 62 % for the ozonated WW effluents. At an EBCT of 15 min, biofilters removed between 7 and 21 % of the DOC (19 to 50 % for BDOC) depending on the DOM type and use of ozonation. When the EBCT decreased to 5 min DOC removal decreased by 40 % and when increased to 30 min removal increased by 42 %. When the temperature decreased from 22 °C to 6 °C DOC removal was 33 % lower and when increased to 28 °C removal was 42 % higher. ATP values were found to be a function of temperature and DOM origin, as the average ATP values from the WW effluent biofilters were almost double that of the non-WW impacted sources and pre-ozonation of the WW effluent yielded values three times higher. The model was applied to the results of 27 different biofilter runs at three EBCTs yielding one distinct rate constant for the non-WW impacted source waters and one rate constant for the WW effluents. The model was successfully applied to the results of 19 filter runs from the literature and to those from a pilot plant over 6 months of operation.

Health Claims and Doses of Fish Oil Supplements in the US.

Importance: One in 5 US adults older than 60 years takes fish oil supplements often for heart health despite multiple randomized clinical trials showing no data for cardiovascular benefit for supplement-range doses. Statements on the supplement labels may influence consumer beliefs about health benefits. Objectives: To evaluate health claims made on the labels of fish oil supplements in the US, and to examine doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in commonly available formulations. Design, Setting, and Participants: This cross-sectional study used data from labels of on-market fish oil (and nonfish ω-3 fatty acid) supplements obtained from the National Institutes of Health Dietary Supplement Label Database. The study was conducted and data analyzed from February to June 2022. Main Outcome and Measures: The frequency and types of health claims made on fish oil labels (US Food and Drug Administration [FDA]-reviewed qualified health claim vs a structure/function claim) and the organ system referenced were evaluated. The total daily doses of combined EPA and DHA (EPA+DHA) were assessed for supplements from 16 leading manufacturers and retailers. Results: Across 2819 unique fish oil supplements, 2082 (73.9%) made at least 1 health claim. Of these, only 399 (19.2%) used an FDA-approved qualified health claim; the rest (1683 [80.8%]) made only structure/function claims (eg, "promotes heart health"). Cardiovascular health claims were the most common (1747 [62.0%]). Across 16 leading brands/manufacturers, 255 fish oil supplements were identified. Among these, substantial variability was found in the daily dose of EPA (median [IQR], 340 [135-647] mg/d), DHA (median [IQR], 270 [140-500] mg/d), and total EPA+DHA (median [IQR], 600 [300-1100] mg/d). Only 24 of 255 supplements (9.4%) evaluated contained a daily dose of 2 g or more EPA+DHA. Conclusions: Results of this cross-sectional study suggest that the majority of fish oil supplement labels make health claims, usually in the form of structure/function claims, that imply a health benefit across a variety of organ systems despite a lack of trial data showing efficacy. Significant heterogeneity exists in the daily dose of EPA+DHA in available supplements, leading to potential variability in safety and efficacy between supplements. Increasing regulation of dietary supplement labeling may be needed to prevent consumer misinformation.

Single cell protein and oil production from solid cocoa fatty acid distillates co-fed ethanol.

The use of solid lipid sidestreams have been overlooked as a feedstock for the production of microbial biomass for food and feed applications and little to no recent work has examined the utilization of solid fatty acid distillates (FADs), which are a significant residue from vegetable oil processing. Yarrowia lipolytica and Rhodosporidium toruloides cultivated on cocoa fatty acid distillates (CFAD) generated final cell dry weight values > 40 g/L, with strong productivity (3.3 g/L·h) and rich protein (>45%) and lipid content (>25%). Interestingly, microbial oils were > 65% unsaturated fatty acids, compared < 20% unsaturated content in FAD. Importantly, to overcome mass-transfer limitations associated with bioconversion of solid lipid residues, ethanol was applied as a co-substrate to solubilize FAD residues. Here, FAD residues from cocoa deodorization have been demonstrated to be high energy feedstocks that represent an attractive substrate for the production of both single cell protein and oil (SCPO).

Challenge in Predicting Persistence to P2Y12 Inhibitors: A Perspective From the ARTEMIS Trial.

Background Premature discontinuation of P2Y12 inhibitor therapy has been associated with adverse cardiac events, which might be preventable by improving medication persistence. Current risk models have limited ability to predict patients at risk of P2Y12 inhibitor nonpersistence. Methods and Results ARTEMIS (Affordability and Real-World Antiplatelet Treatment Effectiveness after Myocardial Infarction Study) was a randomized, controlled trial testing the impact of a copayment assistance intervention on P2Y12 inhibitor persistence and outcomes. Among 6212 patients post myocardial infarction with a planned 1-year course of P2Y12 inhibitor therapy, nonpersistence was defined as a gap in P2Y12 inhibitor filled >30 days by pharmacy fill data. We developed a predictive model for 1-year P2Y12 inhibitor nonpersistence among patients randomized to usual care. P2Y12 inhibitor nonpersistence rates were 23.8% (95% CI, 22.7%-24.8%) at 30 days and 47.9% (46.6%-49.1%) at 1 year; the majority of these patients had in-hospital percutaneous coronary intervention. Patients who received the copayment assistance intervention had nonpersistence rates of 22.0% (20.7%-23.3%) at 30 days and 45.3% (43.8%-46.9%) at 1 year. A 53-variable multivariable model predicting 1-year persistence had a C-index of 0.63 (optimism-corrected C-index 0.58). Model discrimination did not improve with inclusion of patient-reported perceptions about disease, medication-taking beliefs, and prior medication-filling behavior in addition to demographic and medical history data (C-index 0.62). Conclusions Despite addition of patient-reported variables, models predicting persistence with P2Y12 inhibitor therapy performed poorly, thereby suggesting the need for continued patient and clinician education on the importance of P2Y12 inhibitor therapy after acute myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02406677.

Diffusion-Weighted Imaging of the Orbit: A Case Series and Systematic Review.

PURPOSE: To describe the findings of diffusion-weighted imaging (DWI) for a series of orbital lesions and provide a systematic review of relevant literature. METHODS: A retrospective review of 20 patients with orbital lesions who underwent MRI with DWI at two academic institutions between 2015 and 2020 was performed. Lesion diagnosis was histopathologically confirmed except a presumed cavernous hemangioma. Echoplanar diffusion-weighted images had been acquired using 2 or 3 b values (b=0 and 1000 or b=0, 500, and 1000) at 1.5T or 3T. Lesions with significant artifacts were excluded. DWI sequences were analyzed by neuro-radiologists blinded to the diagnosis. Mean ADC values of lesions were calculated from a single region of interest. An independent two-tailed t test was used to compare categories of lesions with p < 0.05 considered significant. A systematic review of the literature was performed. RESULTS: Our study included 21 lesions. ADC values were significantly lower for malignant lesions (0.628 ± 0.125 × 10 -3 mm 2 /s) than inflammatory lesions (1.167 ± 0.381 × 10 -3 mm 2 /s) ( p < 0.001). ADC values were significantly lower for orbital lymphoma (mean 0.621 ± 0.147 × 10 -3 mm 2 /s) than idiopathic orbital inflammation (mean 1.188 ± 0.269 × 10 -3 mm 2 /s) with no overlap ( p < 0.001). CONCLUSIONS: Orbital malignancies demonstrated lower ADC values, while inflammatory processes demonstrated higher ADC values, except IgG4-related disease. DWI and ADC values differentiated idiopathic orbital inflammation from orbital lymphoma. This study highlights the role of DWI in evaluating orbital pathology.

Recurrent Osteomyelitis Caused by Mycobacterium abscessus Necessitating Surgical Decompression and Revision Surgery With Interbody Fusion.

Epidural abscesses can be caused by a number of different organisms, including atypical Mycobacterium. This is a rare case report of an atypical Mycobacterium epidural abscess requiring surgical decompression. Here, we present Mycobacterium abscessus causing a nonpurulent epidural collection surgically treated with laminectomy and washout and discuss clinical clues and radiologic characteristics associated with this condition. A 51-year-old male with a past medical history of chronic intravenous (IV) drug use presented with a three-day history of falls and three-month history of progressively worsening bilateral lower extremity radiculopathy, paresthesias, and numbness. MRI demonstrated an enhancing collection at L2-3 ventral and to the left of the spinal canal causing severe compression of the thecal sac, along with heterogenous contrast enhancement of the L2-3 vertebral bodies and intervertebral disc. The patient was taken for an L2-3 laminectomy and left medial facetectomy, where a fibrous, nonpurulent mass was discovered. Cultures ultimately demonstrated Mycobacterium abscessus subspecies massiliense, and the patient was discharged on IV levofloxacin, azithromycin, and linezolid with complete symptomatic relief. Unfortunately, despite surgical washout and antibiotic coverage, the patient presented twice more, the first time with a recurrent epidural collection requiring repeat drainage and the second time with a recurrent epidural collection with discitis and osteomyelitis with pars fractures requiring repeat epidural drainage and interbody fusion. It is important to recognize that atypical Mycobacterium abscessus can cause a nonpurulent epidural collection, especially in high-risk patients such as those with a history of chronic IV drug use. Additionally, our initial intraoperative findings of a fibrous, adherent mass suggest that in cases where this entity is suspected, surgical decompression should be carefully considered. To this end, the radiologic findings associated with this condition, namely, an enhancing ventral epidural mass involving the disc space, should also be recognized. The notable postoperative course consisting of recurrent collections and osteomyelitis with a pars fracture suggests that early fusion should be considered as an option in these patients. This case report presents clinical and radiologic findings associated with an atypical Mycobacterium discitis and osteomyelitis. The clinical course described herein suggests that early fusion in these patients may provide superior results to decompression alone.

Systolic Anterior Motion of the Mitral Valve in the Presence of Annular Calcification.

BACKGROUND: Mitral annular calcification (MAC) has been reported as a possible cause of systolic anterior motion (SAM) of the mitral valve and dynamic left ventricular outflow tract (LVOT) obstruction. While morphologic features predisposing to SAM in other clinical settings have been described, patients with MAC+SAM have not been systematically investigated. We hypothesized that bulky calcium deposits in the mitral annulus could displace the valve toward the septum, thus promoting development of SAM. METHODS: We studied 30 patients with severe MAC who had SAM with septal contact. Three comparator groups (matched for age and sex) were developed: 30 controls without MAC or SAM, 30 with severe MAC but no SAM, and 30 with SAM but no MAC. RESULTS: Significant differences were found across groups for mitral valve coaptation point-septal distance (CSD), anterior mitral leaflet (AML) length, left ventricular diastolic dimension, and ejection fraction. Comparing all MAC subjects (n = 60) with controls, CSD was less (20.5 ± 4.1 vs 23.2 ± 3.7 mm, P = .003) and ejection fraction was higher (67.7% ± 7.8% vs 60.9% ± 6.4%, P < .0001) in MAC patients. Within MAC subjects AML was longer (21.9 ± 3.0 vs 17.4 ± 2.2 mm, P < .0001) and CSD was smaller (18.0 ± 2.7 vs 23.1 ± 3.6 mm, P < .0001) when SAM was present despite similar height of the calcium bar in the 2 MAC groups (12.4 ± 2.9 vs 11.1 ± 3.1 mm, P = .11). Regression analysis confirmed AML length and CSD as independent predictors of SAM. MAC+SAM patients also had more echocardiographic risk factors for SAM (acute aortomitral angle, small LVOT, long AML, small CSD, and presence of a septal bump) than MAC/no-SAM patients (3.4 ± 0.9 vs 1.8 ± 1.0, P < .0001). CONCLUSIONS: Bulky MAC appears to contribute to dynamic LVOT obstruction when it accumulates in such a way that the mitral valve is displaced anteriorly toward the septum. However, other features are also associated with SAM in these patients, particularly a long AML. A combination of morphologic features and favorable hemodynamics may be needed for SAM to develop in patients with severe MAC.

Use of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagonlike Peptide-1 Receptor Agonists in Patients With Diabetes and Cardiovascular Disease in Community Practice.

Importance: Recent national guidelines recommend sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD); yet, there are limited data on the use of these agents in contemporary community practice. Objective: To evaluate the use of SGLT2i and GLP-1 RA in adults with T2D and ASCVD across a diverse sample of health care systems in the US. Design, Setting, and Participants: This multicenter, retrospective cohort study used electronic health record data from 88 US health care systems participating in Cerner Real World Data between January 2018 to March 2021. Adults with ASCVD and T2D taking at least 1 glucose-lowering medication, had end-stage kidney disease, or had stage 5 chronic kidney disease were excluded. Main Outcomes and Measures: Treatment with SGLT2i or GLP-1 RA. Results: A total of 321 304 patients were identified with T2D and ASCVD ASCVD (130 280 female [40.5%]; median [IQR] age, 70.9 [62.9-78.0] years) who were potentially eligible for SGLT2i and/or GLP-1 RA, including 37 754 Black individuals (11.8%), 51 522 Hispanic individuals (16.0%), and 256 008 White individuals (11.8%). From January 2018 to March 2021, the use of SGLT2i increased from 5.8% (11 285 of 194 264) to 12.9% (11 058 of 85 956), GLP-1 RA increased from 6.9% (13 402 of 194 264) to 13.8% (11 901 of 85 956), and use of either agent increased from 11.4% (22 069 of 194 264) to 23.2% (19 909 of 85 956). Those taking an SGLT2i or GLP-1 RA were younger, less frequently hospitalized in the year prior, and more likely to be taking additional secondary prevention medications. Treated and nontreated populations were similar in terms of race, ethnicity, and outpatient health care utilization. Sulfonylureas and dipeptidyl peptidase 4 inhibitors remained more commonly used than SGLT2i or GLP-1 RA through 2021. Conclusions and Relevance: In this study, uptake of SGLT2i and GLP-1 RA in adults with T2D and ASCVD increased modestly after guideline recommendations, although less than a quarter of persons with ASCVD and T2D receiving medical therapy were taking either. Further efforts are necessary to maximize the potential population benefit of these therapies in this high-risk population.

Does the Effectiveness of a Medicine Copay Voucher Vary by Baseline Medication Out-Of-Pocket Expenses? Insights From ARTEMIS.

Background Persistence to P2Y12 inhibitors after myocardial infarction (MI) remains low. Out-of-pocket cost is cited as a factor affecting medication compliance. We examined whether a copayment intervention affected 1-year persistence to P2Y12 inhibitors and clinical outcomes. Methods and Results In an analysis of ARTEMIS (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study), patients with MI discharged on a P2Y12 inhibitor were stratified by baseline out-of-pocket medication burden: low ($0-$49 per month), intermediate ($50-$149 per month), and high (≥$150 per month). The impact of the voucher intervention on 1-year P2Y12 inhibitor persistence was examined using a logistic regression model with generalized estimating equations. We assessed the rates of major adverse cardiovascular events among the groups using a Kaplan-Meier estimator. Among 7351 MI-treated patients at 282 hospitals, 54.2% patients were in the low copay group, 32.0% in the middle copay group, and 13.8% in the high copay group. Patients in higher copay groups were more likely to have a history of prior MI, heart failure, and diabetes compared with the low copay group (all P<0.0001). Voucher use was associated with a significantly higher likelihood of 1-year P2Y12 inhibitor persistence regardless of copayment tier (low copay with versus without voucher: adjusted odds ratio [OR], 1.44 [95% CI, 1.25-1.66]; middle copay: adjusted OR, 1.63 [95% CI, 1.37-1.95]; high copay group: adjusted OR, 1.41 [95% CI, 1.05-1.87]; P interaction=0.42). Patients in the high copay group without a voucher had similar risk of 1-year major adverse cardiovascular events compared with patients in the high copay group with a voucher (adjusted hazard ratio, 0.89 [95% CI, 0.66-1.21]). Conclusions Medication copayment vouchers were associated with higher medication persistence at 1 year following an MI, regardless of out-of-pocket medication burden. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02406677.

Ninety-Day Risk-Standardized Home Time as a Performance Metric for Cardiac Surgery Hospitals in the United States.

BACKGROUND: Assessing hospital performance for cardiac surgery necessitates consistent and valid care quality metrics. The association of hospital-level risk-standardized home time for cardiac surgeries with other performance metrics such as mortality rate, readmission rate, and annual surgical volume has not been evaluated previously. METHODS: The study included Medicare beneficiaries who underwent isolated or concomitant coronary artery bypass graft, aortic valve, or mitral valve surgery from January 1, 2013, to October 1, 2019. Hospital-level performance metrics of annual surgical volume, 90-day risk-standardized mortality rate, 90-day risk-standardized readmission rate, and 90-day risk-standardized home time were estimated starting from the day of surgery using generalized linear mixed models with a random intercept for the hospital. Correlations between the performance metrics were assessed using the Pearson correlation coefficient. Patient-level clinical outcomes were also compared across hospital quartiles by 90-day risk-standardized home time. Last, the temporal stability of performance metrics for each hospital during the study years was also assessed. RESULTS: Overall, 919 698 patients (age 74.2±5.8 years, 32% women) were included from 1179 hospitals. Median 90-day risk-standardized home time was 71.2 days (25th-75th percentile, 66.5-75.6), 90-day risk-standardized readmission rate was 26.0% (19.5%-35.7%), and 90-day risk-standardized mortality rate was 6.0% (4.0%-8.8%). Across 90-day home time quartiles, a graded decline was observed in the rates of in-hospital, 90-day, and 1-year mortality, and 90-day and 1-year readmission. Ninety-day home time had a significant positive correlation with annual surgical volume (r=0.31; P<0.001) and inverse correlation with 90-day risk-standardized readmission rate (r=-0.40; P <0.001) and 90-day risk-standardized mortality rate (r=-0.60; P <0.001). Use of 90-day home time as a performance metric resulted in a meaningful reclassification in performance ranking of 22.8% hospitals compared with annual surgical volume, 11.6% compared with 90-day risk-standardized mortality rate, and 19.9% compared with 90-day risk-standardized readmission rate. Across the 7 years of the study period, 90-day home time demonstrated the most temporal stability of the hospital performance metrics. CONCLUSIONS: Ninety-day risk-standardized home time is a feasible, comprehensive, patient-centered metric to assess hospital-level performance in cardiac surgery with greater temporal stability than mortality and readmission measures.

Remotely controlled near-infrared-triggered photothermal treatment of brain tumours in freely behaving mice using gold nanostars.

Current clinical brain tumour therapy practices are based on tumour resection and post-operative chemotherapy or X-ray radiation. Resection requires technically challenging open-skull surgeries that can lead to major neurological deficits and, in some cases, death. Treatments with X-ray and chemotherapy, on the other hand, cause major side-effects such as damage to surrounding normal brain tissues and other organs. Here we report the development of an integrated nanomedicine-bioelectronics brain-machine interface that enables continuous and on-demand treatment of brain tumours, without open-skull surgery and toxicological side-effects on other organs. Near-infrared surface plasmon characteristics of our gold nanostars enabled the precise treatment of deep brain tumours in freely behaving mice. Moreover, the nanostars' surface coating enabled their selective diffusion in tumour tissues after intratumoral administration, leading to the exclusive heating of tumours for treatment. This versatile remotely controlled and wireless method allows the adjustment of nanoparticles' photothermal strength, as well as power and wavelength of the therapeutic light, to target tumours in different anatomical locations within the brain.

Cohort study on the differential expression of inflammatory and angiogenic factors in thrombi, cerebral and peripheral plasma following acute large vessel occlusion stroke.

Inflammation plays an important role in the pathogenesis of stroke. The differential expression of inflammatory and angiogenic factors in thrombi and plasma remain undefined. In this observational cohort study, we evaluated angiogenic factors and inflammatory cytokines, in cerebral thrombi, local cerebral plasma (CP), and peripheral plasma (PP) in patients with acute ischemic stroke. Protein analysis of thrombi, CP and PP were used to measure angiogenic and inflammatory proteins using electrochemiluminescence. Our data indicate that VEGF-A, VEGF-C, bFGF, IL-4, IL-13, IL-1ß, IL-2, IL-8, IL-16, IL-6 and IL-12p70 were higher in the thrombi of acute ischemic stroke patients than in the CP and PP of stroke patients. Moreover, the protein levels of GM-CSF were lower in the PP than in the CP and the clot. Moreover, VEGF-D, Flt-1, PIGF, TIE-2, IL-5, TNF-ß, IL-15, IL-12/IL-23p40, IFN-γ and IL-17A were higher in PP and CP than in thrombi. Our results show that cytokines mediating the inflammatory response and proteins involved in angiogenesis are differentially expressed in thrombi within the cerebral and peripheral circulations. These data highlight the importance of identifying new biomarkers in different compartments of the circulatory system and in thrombi that may be used for the diagnosis and treatment of stroke patients.

Pharmacokinetics of bleomycin sclerotherapy in patients with vascular malformations.

Bleomycin, a chemotherapy agent that inhibits synthesis of DNA, has been increasingly utilized in sclerotherapy for patients with vascular malformations. A serious long-term risk of intravenous bleomycin is dose-dependent interstitial pneumonitis. Little is known about absorption and circulating levels of bleomycin when used in sclerotherapy for patients with vascular malformations. This is an Institutional Review Board (IRB)-approved prospective study on patients receiving bleomycin sclerotherapy in the management of vascular malformations. Depending on the type of vascular malformation, bleomycin was administered either in the lumen or interstitial space of the involved lesion. A bleomycin assay measured serum bleomycin plasma concentrations versus time at seven intervals following treatment. Pharmacokinetic parameters were obtained for each participant and included peak plasma concentration (Cmax ), time to reach peak plasma concentration (Tmax ), volume of distribution (Vd ), elimination half-life (t1/2 ), the volume of plasma cleared of the drug per unit time (CL), and total systemic exposure area under the curve (AUC). Fifteen patients were enrolled (5: lymphatic, 4: venous, 6: arteriovenous malformations). Bleomycin was administered interstitially (IS) in 11 patients and intraluminal (IL) in four; median age of 13 years (range: 2-67). Pharmacokinetic analysis revealed terminal elimination half-life (t1/2λz ) of 88.51 (±23.09) and 111.61 (±37.75) minutes for the IS and IL groups, respectively. Vd was 4.86 L (±6.74) and 1.55 L (±0.54) for the IS and IL groups, respectively. AUC was 53.9 (±23.45) and 129.17 (±93.57) mg min/L for the IS and IL groups, respectively. There were no statistically significant differences in t1/2λz , Vd , or AUC parameters between groups. Bleomycin is absorbed systemically when used as a sclerosant for vascular malformations when injected either IS or IL.

Hematologic Complications Associated With Intra-arterial Chemotherapy for Retinoblastoma Treatment: A Single Institution Experience.

Retinoblastoma (RB) is the most common intraocular pediatric malignancy. Advancements in intra-arterial chemotherapy (IAC) for treatment of RB have resulted in dramatic improvement in eye salvage rates. Data regarding IAC outcomes and associated hematologic toxicities are limited. The objective of this retrospective study was to analyze baseline characteristics, efficacy, and hematologic complications associated with IAC treatment in children with RB at a single international referral institution. Ninety-five sessions of IAC were performed in 28 patients. Mean age at RB diagnosis was 12.5 months (SD, 9.2 mo). Fourteen patients had bilateral RB. IAC agents included melphalan, carboplatin, and topotecan. The most common regimens were triple-agent IAC and single-agent melphalan (66.3% and 15.8%, respectively). Median number of IAC sessions was 3 (mean: 3.39, range: 1 to 9). Eye salvage rate was 83.7% with an overall survival rate of 100% at a median follow-up of 29 months (mean: 29.8 mo, range: 1 to 63 mo). A total of 26 patients (92.9%) experienced at least 1 hematologic toxicity during their treatment course Prevalence of neutropenia, anemia, and thrombocytopenia were 89.3%, 85.7%, and 25%, respectively. While IAC is effective in salvaging most eyes with advanced intraocular RB, over half of patients experienced clinically significant neutropenia and anemia. Clinicians should be vigilant in monitoring patients for IAC-related complications.