Longitudinal risk prediction for pediatric glioma with temporal deep learning.

Pediatric glioma recurrence can cause morbidity and mortality; however, recurrence pattern and severity are heterogeneous and challenging to predict with established clinical and genomic markers. Resultingly, almost all children undergo frequent, long-term, magnetic resonance (MR) brain surveillance regardless of individual recurrence risk. Deep learning analysis of longitudinal MR may be an effective approach for improving individualized recurrence prediction in gliomas and other cancers but has thus far been infeasible with current frameworks. Here, we propose a self-supervised, deep learning approach to longitudinal medical imaging analysis, temporal learning, that models the spatiotemporal information from a patient's current and prior brain MRs to predict future recurrence. We apply temporal learning to pediatric glioma surveillance imaging for 715 patients (3,994 scans) from four distinct clinical settings. We find that longitudinal imaging analysis with temporal learning improves recurrence prediction performance by up to 41% compared to traditional approaches, with improvements in performance in both low- and high-grade glioma. We find that recurrence prediction accuracy increases incrementally with the number of historical scans available per patient. Temporal deep learning may enable point-of-care decision-support for pediatric brain tumors and be adaptable more broadly to patients with other cancers and chronic diseases undergoing surveillance imaging.

Heme d formation in a Shewanella benthica hemoglobin.

In our continued investigations of microbial globins, we solved the structure of a truncated hemoglobin from Shewanella benthica, an obligate psychropiezophilic bacterium. The distal side of the heme active site is lined mostly with hydrophobic residues, with the exception of a tyrosine, Tyr34 (CD1) and a histidine, His24 (B13). We found that purified SbHbN, when crystallized in the ferric form with polyethylene glycol as precipitant, turned into a green color over weeks. The electron density obtained from the green crystals accommodated a trans heme d, a chlorin-type derivative featuring a γ-spirolactone and a vicinal hydroxyl group on a pyrroline ring. In solution, exposure of the protein to one equivalent of hydrogen peroxide resulted in a similar green color change, but caused by the formation of multiple products. These were oxidation species released on protein denaturation, likely including heme d, and a species with heme covalently attached to the polypeptide. The Tyr34Phe replacement prevented the formation of both heme d and the covalent linkage. The ready modification of heme b by SbHbN expands the range of chemistries supported by the globin fold and offers a route to a novel heme cofactor.

Stepwise Transfer Learning for Expert-Level Pediatric Brain Tumor MRI Segmentation in a Limited Data Scenario.

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To develop, externally test, and evaluate clinical acceptability of a deep learning (DL) pediatric brain tumor segmentation model using stepwise transfer learning. Materials and Methods In this retrospective study, the authors leveraged two T2-weighted MRI datasets (May 2001-December 2015) from a national brain tumor consortium (n = 184; median age, 7 years (range: 1-23 years); 94 male) and a pediatric cancer center (n = 100; median age, 8 years (range: 1-19 years); 47 male) to develop and evaluate DL neural networks for pediatric low-grade glioma segmentation using a novel stepwise transfer learning approach to maximize performance in a limited data scenario. The best model was externally-tested on an independent test set and subjected to randomized, blinded evaluation by three clinicians, wherein they assessed clinical acceptability of expert- and artificial intelligence (AI)-generated segmentations via 10-point Likert scales and Turing tests. Results The best AI model used in-domain, stepwise transfer learning (median DSC: 0.88 [IQR 0.72-0.91] versus 0.812 [0.56-0.89] for baseline model; P = .049). On external testing, AI model yielded excellent accuracy using reference standards from three clinical experts (Expert-1: 0.83 [0.75-0.90]; Expert-2: 0.81 [0.70-0.89]; Expert-3: 0.81 [0.68-0.88]; mean accuracy: 0.82)). On clinical benchmarking (n = 100 scans), experts rated AI-based segmentations higher on average compared with other experts (median Likert score: median 9 [IQR 7-9]) versus 7 [IQR 7-9]) and rated more AI segmentations as clinically acceptable (80.2% versus 65.4%). Experts correctly predicted the origin of AI segmentations in an average of 26.0% of cases. Conclusion Stepwise transfer learning enabled expert-level, automated pediatric brain tumor auto-segmentation and volumetric measurement with a high level of clinical acceptability. ©RSNA, 2024.

The Association Between Surgeon Volume and Dislocation After Total Hip Arthroplasty: A Nationwide Evaluation of 5,106 Orthopaedic Surgeons.

INTRODUCTION: The relationship between surgeon volume and risk of dislocation after total hip arthroplasty (THA) is debated. This study sought to characterize this association and assess patient outcomes using a nationwide patient and surgeon registry. METHODS: The Premier Healthcare Database was queried for adult primary elective THA patients from January 1, 2016, to December 31, 2019. Annual surgeon volume and 90-day risk of dislocation were modeled using multivariable logistic regression with restricted cubic splines. Bootstrap analysis identified a threshold annual case volume, corresponding to the maximum decrease in dislocation risk. Surgeons with an annual volume greater than the threshold were deemed high volume, and those with an annual volume less than the threshold were low volume. Each surgeon within a given year was treated as a unique entity (surgeon-year unit). 90-day complications of patients treated by high-volume and low-volume surgeons were compared. RESULTS: From 2016 to 2019, 352,131 THAs were performed by 5,106 surgeons. The restricted cubic spline model demonstrated an inverse relationship between risk of dislocation and surgeon volume (threshold: 109 cases per year). A total of 9,967 (87.8%) low-volume surgeon-year units had individual dislocation rates lower than the average of the entire surgeon cohort. Patients treated by high-volume surgeons had decreased risk of dislocation (adjusted odds ratio [aOR], 0.60; 95% CI, 0.54 to 0.67), periprosthetic fracture (aOR, 0.87; 95% CI, 0.76 to 0.99), periprosthetic joint infection (aOR, 0.63; 95% CI, 0.56 to 0.69), readmission (aOR, 0.70; 95% CI, 0.67 to 0.73), and in-hospital death (aOR, 0.60; 95% CI, 0.46 to 0.80). CONCLUSION: While most of the low-volume surgeons had dislocation rates lower than the cohort average, increasing annual surgeon case volume was associated with a reduction in risk of dislocation after primary elective THA. THERAPEUTIC LEVEL OF EVIDENCE: Level IV.

Case Report: Low-grade glioma with NF1 loss of function mimicking diffuse intrinsic pontine glioma.

Intrinsic, expansile pontine tumors typically occur in the pediatric population. These tumors characteristically present as diffuse intrinsic pontine glioma (DIPG), which is now considered as diffuse midline glioma (DMG), H3K27-mutated of the pons. DIPG has limited treatment options and a poor prognosis, and the value of tissue diagnosis from an invasive biopsy remains controversial. This study presents the case of a 19-year-old female with clinical and imaging hallmarks of DIPG, who underwent a biopsy of a tumor in the region of the right middle cerebellar peduncle. Her lesional cells were negative for H3K27M alterations and had low-grade histologic features. Next-generation sequencing revealed a frameshift mutation in the NF1 gene as the likely driver mutation. These features suggest a diagnosis of a low-grade glioma associated with NF1 loss of function, with far-reaching consequences regarding both treatment strategy and prognosis. This case provides support for the utility of diagnostic tissue biopsy in cases of suspected DIPG.

Modeling interactions between Heparan sulfate and proteins based on the Heparan sulfate microarray analysis.

Heparan sulfate (HS), a sulfated polysaccharide abundant in the extracellular matrix, plays pivotal roles in various physiological and pathological processes by interacting with proteins. Investigating the binding selectivity of HS oligosaccharides to target proteins is essential, but the exhaustive inclusion of all possible oligosaccharides in microarray experiments is impractical. To address this challenge, we present a hybrid pipeline that integrates microarray and in silico techniques to design oligosaccharides with desired protein affinity. Using fibroblast growth factor 2 (FGF2) as a model protein, we assembled an in-house dataset of HS oligosaccharides on microarrays and developed two structural representations: a standard representation with all atoms explicit and a simplified representation with disaccharide units as "quasi-atoms." Predictive Quantitative Structure-Activity Relationship (QSAR) models for FGF2 affinity were developed using the Random Forest (RF) algorithm. The resulting models, considering the applicability domain, demonstrated high predictivity, with a correct classification rate of 0.81-0.80 and improved positive predictive values (PPV) up to 0.95. Virtual screening of 40 new oligosaccharides using the simplified model identified 15 computational hits, 11 of which were experimentally validated for high FGF2 affinity. This hybrid approach marks a significant step toward the targeted design of oligosaccharides with desired protein interactions, providing a foundation for broader applications in glycobiology.

Serum Creatinine as an Independent Predictor of Moderate to Severe Fibrosis in Chinese American Non-obese Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to the obesity epidemic. However, non-obese MASLD (body mass index [BMI] < 25 kg/m2 for Asians) is not uncommon, especially among Asian American populations. Preliminary research has demonstrated sarcopenia, a muscle-wasting syndrome, to be a major risk factor for non-obese Chinese MASLD. This study examined serum creatinine (SCr), a sarcopenia biomarker, and other prominent MASLD biomarkers for their ability to predict moderate to severe fibrosis (≥7.5 kPa or ≥F2 fibrosis) in the Chinese American MASLD population. METHODS: A total of 296 Chinese American MASLD patients were categorized by BMI and fibrosis severity. As per World Health Organization guidelines for Asians, we identified obese MASLD (BMI ≥ 25 kg/m2) in 191 subjects (64.5%) and non-obese MASLD (BMI < 25 kg/m2) in 105 subjects (35.5%). Multivariate logistic regressions were performed to ascertain which biomarkers served as independent predictors of ≥F2 fibrosis. Wilcoxon signed-rank tests were conducted to compare MASLD cohorts (stratified by gender) and the healthy adult population on SCr distribution. RESULTS: The obese MASLD cohorts had higher rates of ≥F2 fibrosis and type 2 diabetes mellitus compared to their older, non-obese counterparts. For obese MASLD patients, higher age (P < 0.05), increased BMI (P < 0.01), increased AST (P < 0.05), and decreased platelets (P < 0.05) independently predicted ≥F2 fibrosis. For non-obese MASLD patients, lowered SCr (P < 0.05) levels served as the main predictor of ≥F2 fibrosis. Female MASLD patients had markedly lower SCr distributions (P < 0.001) compared to the healthy female population, with 26.8% having SCr levels below the normal range. CONCLUSIONS: In summary, SCr was the predominant predictor of moderate to severe fibrosis in non-obese Chinese American MASLD patients. The high rate of decreased SCr levels in Chinese American MASLD women suggests that this population may be at higher risk for muscle mass loss, which can lead to liver fat accumulation.

On the acceptance, commissioning, and quality assurance of electron FLASH units.

Background & Purpose: FLASH or ultra-high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an example of commissioning. Methods: A protocol for acceptance, commissioning, and QA of UHDR linear accelerators was established by combining and adapting standards and professional recommendations for standard linear accelerators based on the experience with UHDR at four clinical centers that use different UHDR devices. Non-standard dosimetric beam parameters considered included pulse width, pulse repetition frequency, dose per pulse, and instantaneous dose rate, together with recommendations on how to acquire these measurements. Results: The 6- and 9-MeV beams of an UHDR electron device were commissioned by using this developed protocol. Measurements were acquired with a combination of ion chambers, beam current transformers (BCTs), and dose-rate-independent passive dosimeters. The unit was calibrated according to the concept of redundant dosimetry using a reference setup. Conclusions: This study provides detailed recommendations for the acceptance testing, commissioning, and routine QA of low-energy electron UHDR linear accelerators. The proposed framework is not limited to any specific unit, making it applicable to all existing eFLASH units in the market. Through practical insights and theoretical discourse, this document establishes a benchmark for the commissioning of UHDR devices for clinical use.

Herpes zoster ophthalmicus (HZO) recurrence: risk factors and long-term clinical outcomes.

PURPOSE: To examine the frequency of recurrences, risk factors and long-term clinical outcomes in subjects with herpes zoster ophthalmicus (HZO). DESIGN: Retrospective cohort study. METHODS: All subjects with acute HZO seen at a single centre from 2006 to 2016 were included in the study. The primary outcome measure was eye disease recurrence. The secondary outcome measure was moderate vision loss (≤20/50). RESULTS: A total of 869 patients with acute HZO were identified with a median follow-up time of 6.3 years (interquartile range 3.7-8.9 years). 551 recurrences were observed, and at least one recurrence was seen in 200 subjects (23.0%), with uveitis (34.8%) being most common. The median time to first recurrence was 3.5 months. Predictors of disease recurrence included immunosuppression (p=0.026), higher presenting intraocular pressure (p=0.001), corneal involvement (p=0.001), and uveitis (p<0.001) on multivariate analysis. Topical steroids were initiated in the first month of presentation for 437 subjects, and recurrence was observed in 184 (42.1%) of these subjects. Following cessation of topical steroid treatment, recurrence occurred after a median of 1.4 months (90% within 7 months). Moderate vision loss (≤ 20/50) occurred in 15.5%, 28.6%, 31.4%, 50.0% and 57.4% of eyes with zero, one, two, three, and four or more recurrences. CONCLUSIONS: Recurrence of HZO eye disease is common, with an increased risk of vision loss with more recurrences. These findings indicate the need for close monitoring for potential recurrences, especially after cessation of topical steroid treatment, and in those with identified risk factors for recurrence.

Preoperative Laboratory Values Predicting Periprosthetic Joint Infection in Morbidly Obese Patients Undergoing Total Hip or Knee Arthroplasty.

BACKGROUND: Morbidly obese patients are an ever-growing high-risk population undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) for end-stage osteoarthritis. This study sought to identify preoperative laboratory values that may serve as predictors of periprosthetic joint infection (PJI) in morbidly obese patients undergoing THA or TKA. METHODS: All morbidly obese patients with preoperative laboratory data before undergoing primary elective TKA or THA were identified using the Premier Healthcare Database. Patients who developed PJI within 90 days after surgery were compared with patients without PJI. Laboratory value thresholds were defined by clinical guidelines or primary literature. Univariate and multivariable regression analyses were utilized to assess the association between PJI and preoperative laboratory values, including total lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), albumin level, platelet count, albumin-globulin ratio, hemoglobin level, and hemoglobin A1c. RESULTS: Of the 6,780 patients identified (TKA: 76.67%; THA: 23.33%), 47 (0.69%) developed PJI within 90 days after surgery. The rate of PJI was 1.69% for patients with a hemoglobin level of <12 g/dL (for females) or <13 g/dL (for males), 2.14% for those with a platelet count of <142,000/µL or >417,000/µL, 1.11% for those with an NLR of >3.31, 1.69% for those with a PLR of >182.3, and 1.05% for those with an SII of >776.2. After accounting for potential confounding factors, we observed an association between PJI and an abnormal preoperative NLR (adjusted odds ratio [aOR]: 2.38, 95% confidence interval [CI]: 1.04 to 5.44, p = 0.039), PLR (aOR: 4.86, 95% CI: 2.15 to 10.95, p < 0.001), SII (aOR: 2.44, 95% CI: 1.09 to 5.44, p = 0.029), platelet count (aOR: 3.50, 95% CI: 1.11 to 10.99, p = 0.032), and hemoglobin level (aOR: 2.62, 95% CI: 1.06 to 6.50, p = 0.038). CONCLUSIONS: This study identified preoperative anemia, abnormal platelet count, and elevated NLR, PLR, and SII to be associated with an increased risk of PJI among patients with a body mass index of ≥40 kg/m 2 . These findings may help surgeons risk-stratify this high-risk patient population. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Complete Blood Count Ratios Predict Adverse Events After Total Joint Arthroplasty.

INTRODUCTION: Complete blood count-based ratios (CBRs), including neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are biomarkers associated with the proinflammatory surgical stress response. This study sought to determine whether preoperative CBRs are associated with postoperative complications, protracted hospital length of stay (LOS), and mortality after total joint arthroplasty, as well as establish threshold values for these outcomes for use in future investigations. METHODS: The Premier Healthcare Database was retrospectively queried for adult patients who underwent primary elective total hip arthroplasty or total knee arthroplasty (TKA). Approximate cut-point values for CBRs were identified by bootstrap simulation using the Youden index. Multivariable adjusted restricted cubic spline models using the predicted cut-point value as the threshold for odds of outcomes were created to identify a final threshold value associated with increased adjusted odds ratio (aOR) of study outcomes. RESULTS: A total of 32,868 total joint arthroplasties (THA: 12,807, TKA: 20,061) were identified. All measures predicted odds of aggregate postoperative complications (THA: NLR TV: 4.60 [aOR = 2.35], PLR TV: 163.4 [aOR = 1.32], MLR TV: 0.40 [aOR = 2.02], SII TV: 977.00 [aOR = 1.54]; TKA: NLR TV: 3.7 [aOR = 1.69], MLR TV: 0.41 [aOR = 1.62], PLR TV: 205.10 [aOR = 1.43], SII TV: 1,013.10 [aOR = 1.62]; all P < 0.05). A MLR > 0.40 [aOR = 1.54] P < 0.001) was associated with LOS ≥3 days after total hip arthroplasty while an NLR > 13.1 [aOR = 1.38] and an MLR > 0.41[aOR = 1.29] were associated with LOS ≥3 days after total knee arthroplasty (both P < 0.001). No association between inflammatory markers and inpatient mortality was observed. CONCLUSION: Given CBRs' ability to both predict outcomes and identify patients with a proinflammatory phenotype, the findings of this study provide a framework for future investigations aimed at identifying and treating high-risk patients with immune-modulating therapies. Continued work to validate these findings by applying TVs to interventional clinical trials is needed before wide clinical adoption.

Chromatic bleaching and fractionation effects on optically stimulated luminescent dosimeter reuse.

BACKGROUND: Optically stimulated luminescent dosimeters (OSLDs) can be bleached and reused, but questions remain about the effects of repeated bleaching and fractionation schedules on OSLD performance. PURPOSE: The aim of this study was to investigate how light sources with different wavelengths and different fractionation schemes affect the performance of reused OSLDs. METHODS: OSLDs (N = 240) were irradiated on a cobalt-60 beam in different step sizes until they reached an accumulated dose of 50 Gy. Between irradiations they were bleached using light sources of different wavelengths: the Imaging and Radiation Oncology Core (IROC) bleaching system (our control); monochromatic red, green, yellow, and blue lights; and a polychromatic white light. Sensitivity and linearity-based correction factors were determined as a function of dose step-size. The rate of signal removal from different light sources was characterized by sampling these OSLDs at various time points during their bleaching process. Relative doses were calculated according to the American Association of Physicists in Medicine Task Group-191. Signal repopulation was investigated by irradiating OSLDs (N = 300) to various delivered doses of 2, 10, 20, 30, 40, and 50 Gy in a single fraction, bleached with one of the colors, and read over time. Fractionation effects were evaluated by irradiating OSLDs up to 30 Gy in different size steps. After reading, the OSLDs were bleached following IROC protocol. OSLDs (N = 40) received irradiations in 5, 10, 15, 30 Gy fractions until they had an accumulated dose of 30 Gy; The sensitivity response of these OSLDs was compared with reference OSLDs that had no accumulated dose. RESULTS: Light sources with polychromatic spectrums (IROC and white) bleached OSLDs faster than did sources with monochromatic spectra. Polychromatic light sources (white light and IROC system) provided the greatest dose stability for OSLDs that had larger amounts of accumulated dose. Signal repopulation was related to the choice of bleaching light source, timing of bleaching, and amount of accumulated dose. Changes to relative dosimetry were more pronounced in OSLDs that received larger fractions. At 5-Gy fractions and above, all OSLDs had heightened sensitivity, with OSLDs exposed to 30-Gy fractions being 6.4% more sensitive than reference dosimeters. CONCLUSIONS: The choice of bleaching light plays a role in how fast an OSLD is bleached and how much accumulated dose an OSLD can be exposed to while maintaining stable signal sensitivity. We have expanded upon investigations into signal repopulation to show that bleaching light plays a role in the migration of deep traps to dosimetric traps after bleaching. Our research concludes that the bleaching light source and fractionation need to be considered when reusing OSLD.

Patterns of recurrence after radiotherapy for high-risk neuroblastoma: Implications for radiation dose and field.

BACKGROUND: Prognosis for patients with high-risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields. METHODS: Multi-institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997-2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis. Follow-up was defined from the end of EBRT. Event-free survival (EFS) and OS were analyzed by Kaplan-Meier method. Cumulative incidence of locoregional progression (CILP) was analyzed using competing risks of distant-only relapse and death with Gray's test. RESULTS: Median follow-up was 7.0 years (range: 0.01-22.4). Five-year CILP, EFS, and OS were 11.9 %, 65.2 %, and 77.5 %, respectively. Of the 31 patients with LRR and imaging review, 15 (48.4 %) had in-field recurrences (>12 Gy), 6 (19.4 %) had marginal failures (≤12 Gy), and 10 (32.3 %) had both in-field and marginal recurrences. No patients receiving total body irradiation (12 Gy) experienced marginal-only failures (p = 0.069). On multivariable analyses, MYCN amplification had higher risk of LRR (HR: 2.42, 95 % CI: 1.06-5.50, p = 0.035) and post-consolidation isotretinoin and anti-GD2 antibody therapy (HR: 0.42, 95 % CI: 0.19-0.94, p = 0.035) had lower risk of LRR. CONCLUSIONS: Despite EBRT, LRR remains a contributor to treatment failure in HR-NBL with approximately half of LRRs including a component of marginal failure. Future prospective studies are needed to explore whether radiation fields and doses should be defined based on molecular features such as MYCN amplification, and/or response to chemotherapy.

Perioperative Dexamethasone is Associated With a Decreased Risk of Pulmonary Embolism and Deep Vein Thrombosis Following Total Joint Arthroplasty: An Analysis of 70,000 High-Risk Patients.

BACKGROUND: Dexamethasone (DEX) has demonstrated promise with respect to decreasing postoperative thromboembolic complications following total joint arthroplasty (TJA). Therefore, the aim of this study was to investigate the effects of perioperative intravenous DEX on rates of pulmonary embolism (PE) and deep vein thrombosis (DVT) after primary TJA in patients who have a history of venous thromboembolism (VTE). METHODS: Patients who have a history of VTE who underwent primary elective TJA from 2015 to 2021 were identified using a commercial health care database. Patients were divided based on receipt of perioperative intravenous DEX [DEX(+) versus DEX(-)] on the day of index TJA. Patient demographics and hospital factors were collected. The 90-day risk of postoperative complications, readmission, and in-hospital mortality were compared. RESULTS: Overall, 70,147 patients who had a history of VTE underwent TJA, of which 40,607 (57.89%) received DEX and 29,540 (42.11%) did not. The DEX(+) patients were younger (67 ± 9.8 versus 68 ± 9.9 years, P < .001) and had a significantly shorter length of stay compared to the DEX(-) patients (1.8 ± 1.6 versus 2.2 ± 1.8 days, P < .001). The DEX(+) patients demonstrated lower rates of PE (1.37 versus 1.75%, P < .001) and DVT (2.37 versus 3.01%, P < .001) compared to DEX(-) patients. The DEX(+) patients experienced a lower risk of PE (adjusted odds ratio: 0.78, 95% confidence interval: 0.66 to 0.93, P = .006) and DVT (adjusted odds ratio: 0.84, 95% confidence interval: 0.74 to 0.95, P = .006) compared to DEX(-) patients. The DEX(+) patients demonstrated no differences in the odds of surgical site infection, periprosthetic joint infection, or sepsis compared to the DEX(-) patients (P > .05). CONCLUSIONS: The administration of DEX was associated with a decreased risk of PE and DVT in patients who have a history of VTE who underwent TJA. These data warrant further study investigating the postoperative benefits of perioperative DEX administration for high-risk patients undergoing TJA. LEVEL OF EVIDENCE: Level III.

Redefining FLASH RT: the impact of mean dose rate and dose per pulse in the gastrointestinal tract.

Background: The understanding of how varying radiation beam parameter settings affect the induction and magnitude of the FLASH effect remains limited. Purpose: We sought to evaluate how the magnitude of radiation-induced gastrointestinal (GI) toxicity (RIGIT) depends on the interplay between mean dose rate (MDR) and dose per pulse (DPP). Methods: C57BL/6J mice were subjected to total abdominal irradiation (11-14 Gy single fraction) under conventional irradiation (low DPP and low MDR, CONV) and various combinations of DPP and MDR up to ultra-high-dose-rate (UHDR) beam conditions. The effects of DPP were evaluated for DPPs of 1-6 Gy while the total dose and MDR were kept constant; the effects of MDR were evaluated for the range 0.3- 1440 Gy/s while the total dose and DPP were kept constant. RIGIT was quantified in non-tumor-bearing mice through the regenerating crypt assay and survival assessment. Tumor response was evaluated through tumor growth delay. Results: Within each tested total dose using a constant MDR (>100 Gy/s), increasing DPP led to better sparing of regenerating crypts, with a more prominent effect seen at 12 and 14 Gy TAI. However, at fixed DPPs >4 Gy, similar sparing of crypts was demonstrated irrespective of MDR (from 0.3 to 1440 Gy/s). At a fixed high DPP of 4.7 Gy, survival was equivalently improved relative to CONV for all MDRs from 0.3 Gy/s to 104 Gy/s, but at a lower DPP of 0.93 Gy, increasing MDR produced a greater survival effect. We also confirmed that high DPP, regardless of MDR, produced the same magnitude of tumor growth delay relative to CONV using a clinically relevant melanoma mouse model. Conclusions: This study demonstrates the strong influence that the beam parameter settings have on the magnitude of the FLASH effect. Both high DPP and UHDR appeared independently sufficient to produce FLASH sparing of GI toxicity, while isoeffective tumor response was maintained across all conditions.

Prescription drug monitoring programs and prescription pain medication misuse among U.S. high school students-2019.

BACKGROUND: Prescription drug monitoring programs (PDMPs) are state-level databases that track and inform prescribing practices to reduce prescription drug diversion and misuse. To our knowledge, only three studies have examined the impact of PDMPs on opioid-related outcomes among adolescents, and none have focused on prescription pain medication misuse among adolescents. METHODS: This study leveraged data from the 2019 National Youth Risk Behavior Survey (YRBS) to explore the associations between five categories of PDMP dimensions and the prevalence of self-reported prescription pain medication misuse. Demographic factors' associations with self-reported prescription pain medication misuse were also examined. RESULTS: In 2019, none of the PDMP dimensions were associated with self-reported prescription pain medication misuse among U.S. high school students, adjusting for gender, grade, race/ethnicity, and sexual orientation. CONCLUSIONS: None of the five PDMP dimensions were associated with lower prescription pain medication misuse, however further research is needed, especially as new YRBS data become available.

Risk Factors Associated with Thromboembolic Complications After total Hip Arthroplasty: An Analysis of 1,129 Pulmonary Emboli.

INTRODUCTION: Venous thromboembolism (VTE) remains a dangerous complication after total hip arthroplasty (THA), despite advances in chemoprophylactic measures. This study aimed to identify risk factors of developing pulmonary embolism (PE) and deep vein thrombosis (DVT) after THA using a modern cohort of patients reflecting contemporary practices. METHODS: The Premier Healthcare Database was queried for primary, elective THAs from January 1st, 2015, to December 31st, 2021. Patients who developed PE or DVT within 90 days of THA were compared with patients who did not develop any postoperative VTE. Differences in patient demographics, comorbidities, hospital factors, perioperative medications, chemoprophylactic agents, and allogeneic blood transfusion were compared between cohorts. Multivariable logistic regression models were used to identify independent risk factors of PE and DVT. In total, 544,298 THAs were identified, of which 1,129 (0.21%) developed a PE and 1,799 (0.33%) developed a DVT. RESULTS: Patients diagnosed with a PE had significantly higher rates of in-hospital death (2.6% vs 0.1%, P < 0.001) compared with those without a PE. Age (adjusted odds ratio: 1.02 per year, 95% confidence interval [CI]: 1.01 to 1.03) and Black race (aOR: 1.52, 95% CI: 1.24 to 1.87) were associated with an increased risk of PE. Comorbidities associated with increased risk of PE included chronic pulmonary disease (aOR: 1.58, 95% CI: 1.36 to 1.84), pulmonary hypertension (aOR: 2.06, 95% CI: 1.39 to 3.04), and history of VTE (aOR: 2.38, 95% CI: 1.98 to 2.86). Allogeneic blood transfusion (aOR: 2.40, 95% CI: 1.88 to 3.06) was also associated with an increased risk of PE while dexamethasone utilization was associated with a reduced risk (aOR: 0.83, 95% CI: 0.73 to 0.95). DISCUSSION: Increasing age; Black race; allogeneic blood transfusion; and comorbidities, including chronic pulmonary disease, pulmonary hypertension, and history of VTE, were independent risk factors of PE after THA. Given the increased mortality associated with PE, patients should be carefully evaluated for these factors and managed with an appropriate chemoprophylactic regimen.

Multi-Institutional Audit of FLASH and Conventional Dosimetry With a 3D Printed Anatomically Realistic Mouse Phantom.

PURPOSE: We conducted a multi-institutional dosimetric audit between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3-dimensional (3D) printed mouse phantom. METHODS AND MATERIALS: A computed tomography (CT) scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene (∼1.02 g/cm3) and polylactic acid (∼1.24 g/cm3) simultaneously to simulate soft tissue and bone densities, respectively. The lungs were printed separately using lightweight polylactic acid (∼0.64 g/cm3). Hounsfield units (HU), densities, and print-to-print stability of the phantoms were assessed. Three institutions were each provided a phantom and each institution performed 2 replicates of irradiations at selected anatomic regions. The average dose difference between FLASH and CONV dose distributions and deviation from the prescribed dose were measured with radiochromic film. RESULTS: Compared with the reference CT scan, CT scans of the phantom demonstrated mass density differences of 0.10 g/cm3 for bone, 0.12 g/cm3 for lung, and 0.03 g/cm3 for soft tissue regions. Differences in HU between phantoms were <10 HU for soft tissue and bone, with lung showing the most variation (54 HU), but with minimal effect on dose distribution (<0.5%). Mean differences between FLASH and CONV decreased from the first to the second replicate (4.3%-1.2%), and differences from the prescribed dose decreased for both CONV (3.6%-2.5%) and FLASH (6.4%-2.7%). Total dose accuracy suggests consistent pulse dose and pulse number, although these were not specifically assessed. Positioning variability was observed, likely due to the absence of robust positioning aids or image guidance. CONCLUSIONS: This study marks the first dosimetric audit for FLASH using a nonhomogeneous phantom, challenging conventional calibration practices reliant on homogeneous phantoms. The comparison protocol offers a framework for credentialing multi-institutional studies in FLASH preclinical research to enhance reproducibility of biologic findings.

A comprehensive investigation of the performance of a commercial scintillator system for applications in electron FLASH radiotherapy.

BACKGROUND: Dosimetry in ultra-high dose rate (UHDR) beamlines is significantly challenged by limitations in real-time monitoring and accurate measurement of beam output, beam parameters, and delivered doses using conventional radiation detectors, which exhibit dependencies in ultra-high dose-rate (UHDR) and high dose-per-pulse (DPP) beamline conditions. PURPOSE: In this study, we characterized the response of the Exradin W2 plastic scintillator (Standard Imaging, Inc.), a water-equivalent detector that provides measurements with a time resolution of 100 Hz, to determine its feasibility for use in UHDR electron beamlines. METHODS: The W2 scintillator was exposed to an UHDR electron beam with different beam parameters by varying the pulse repetition frequency (PRF), pulse width (PW), and pulse amplitude settings of an electron UHDR linear accelerator system. The response of the W2 scintillator was evaluated as a function of the total integrated dose delivered, DPP, and mean and instantaneous dose rate. To account for detector radiation damage, the signal sensitivity (pC/Gy) of the W2 scintillator was measured and tracked as a function of dose history. RESULTS: The W2 scintillator demonstrated mean dose rate independence and linearity as a function of integrated dose and DPP for DPP ≤ 1.5 Gy (R2 > 0.99) and PRF ≤ 90 Hz. At DPP > 1.5 Gy, nonlinear behavior and signal saturation in the blue and green signals as a function of DPP, PRF, and integrated dose became apparent. In the absence of Cerenkov correction, the W2 scintillator exhibited PW dependence, even at DPP values <1.5 Gy, with a difference of up to 31% and 54% in the measured blue and green signal for PWs ranging from 0.5 to 3.6 µs. The change in signal sensitivity of the W2 scintillator as a function of accumulated dose was approximately 4%/kGy and 0.3%/kGy for the measured blue and green signal responses, respectively, as a function of integrated dose history. CONCLUSION: The Exradin W2 scintillator can provide output measurements that are both dose rate independent and linear in response if the DPP is kept ≤1.5 Gy (corresponding to a mean dose rate up to 290 Gy/s in the used system), as long as proper calibration is performed to account for PW and changes in signal sensitivity as a function of accumulated dose. For DPP > 1.5 Gy, the W2 scintillator's response becomes nonlinear, likely due to limitations in the electrometer related to the high signal intensity.

ALT to qHBsAg ratio predicts long-term HBsAg seroclearance after entecavir cessation in Chinese patients with chronic hepatitis B.

BACKGROUND & AIMS: Factors predicting HBsAg seroclearance after treatment cessation, irrespective of nucleos(t)ide analogue (NA) resumption, have important clinical implications. We evaluated predictors of long-term HBsAg seroclearance after entecavir cessation. METHODS: This study followed-up Chinese patients with chronic hepatitis B from two previous studies of entecavir cessation. All patients were non-cirrhotic, HBeAg-negative, with undetectable HBV DNA (<20 IU/ml) at end-of-treatment (EOT). They were monitored closely for 48 weeks with regular HBV DNA, quantitative HBsAg (qHBsAg) and alanine aminotransferase (ALT) measurements. Entecavir was resumed at HBV DNA >2,000 IU/ml, irrespective of ALT levels. After the initial 48 weeks, patients were assessed every 6 months, regardless of entecavir resumption, to monitor for HBsAg seroclearance. RESULTS: A total of 194 patients (63.4% male, mean age 49.9 years, on entecavir for a median of 47.2 months) were recruited; 94 (48.5%) and 158 (81.4%) patients had EOT qHBsAg <100 IU/ml and <1,000 IU/ml, respectively; 151 (77.8%) patients were eventually resumed on entecavir. After follow-up for a median of 70.7 (51.0-118.2) months, 28 (14.4%) patients had HBsAg seroclearance. qHBsAg levels at weeks 36 and 48 after EOT independently predicted HBsAg seroclearance (both p <0.01), whereas qHBsAg from EOT to week 24 only trended towards statistical significance. The ratio of ALT/qHBsAg at all time points from EOT to week 48 independently predicted HBsAg seroclearance (hazard ratios ranging from 1.003-1.028, all p <0.01) with excellent diagnostic performance (area under the receiver-operating characteristic curve 0.799-0.933, negative predictive value >90% at different time points), regardless of whether entecavir was resumed. CONCLUSIONS: The ALT/qHBsAg ratio after entecavir cessation predicts HBsAg seroclearance, even in patients who were resumed on treatment. Its use may mitigate the risk of severe hepatitis flares in patients managed by observation without treatment resumption. IMPACT AND IMPLICATIONS: Current predictors of HBsAg seroclearance after finite nucleos(t)ide analogue (NA) therapy have suboptimal predictive value. We demonstrated that the ALT/qHBsAg ratio may be able to reflect the balance between host control and virological activity. The ALT/qHBsAg ratio at different time points from end-of-treatment till week 48 independently and accurately predicted HBsAg seroclearance in patients who have stopped entecavir. The ALT/qHBsAg ratio may be utilized by clinicians for patient selection and retreatment decisions in finite NA therapy.