Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys.

The development of immunologic interventions that can target the viral reservoir in HIV-1-infected individuals is a major goal of HIV-1 research. However, little evidence exists that the viral reservoir can be sufficiently targeted to improve virologic control following discontinuation of antiretroviral therapy. Here we show that therapeutic vaccination with Ad26/MVA (recombinant adenovirus serotype 26 (Ad26) prime, modified vaccinia Ankara (MVA) boost) and stimulation of TLR7 (Toll-like receptor 7) improves virologic control and delays viral rebound following discontinuation of antiretroviral therapy in SIV-infected rhesus monkeys that began antiretroviral therapy during acute infection. Therapeutic vaccination with Ad26/MVA resulted in a marked increase in the magnitude and breadth of SIV-specific cellular immune responses in virologically suppressed, SIV-infected monkeys. TLR7 agonist administration led to innate immune stimulation and cellular immune activation. The combination of Ad26/MVA vaccination and TLR7 stimulation resulted in decreased levels of viral DNA in lymph nodes and peripheral blood, and improved virologic control and delayed viral rebound following discontinuation of antiretroviral therapy. The breadth of cellular immune responses correlated inversely with set point viral loads and correlated directly with time to viral rebound. These data demonstrate the potential of therapeutic vaccination combined with innate immune stimulation as a strategy aimed at a functional cure for HIV-1 infection.

Prevalence and Epidemiology of Mycoplasma genitalium in a Pacific-Region Military Population.

BACKGROUND: Mycoplasma genitalium is an important emerging sexually transmitted pathogen commonly causing urethritis in men, cervicitis, and pelvic inflammatory disease in women with potential of infertility. Accumulating evidence identifies the prevalence of M. genitalium similar to long recognized pathogens, Chlamydia trachomatis and Neisseria gonorrhoeae. The purpose of this study was to establish the prevalence and epidemiology of M. genitalium in a mid-Pacific military population. METHODS: A prospective analysis was conducted from routine specimens collected as standard of care for sexually transmitted infection (STI) testing at Tripler Army Medical Center on Oahu, HI. The prevalence of M. genitalium was determined using the Aptima M. genitalium assay, a transcription-mediated amplification test. A multivariate analysis was performed to assess the associations for this infection with other STIs and demographic factors. RESULTS: A total of 1876 specimens were tested in a 6-month period including 6 sample types from 1158 females and 718 males. Subject ages ranged from 18 to 76 years, with a median of 24 years (interquartile range, 21-29 years). The prevalence of M. genitalium was 8.8% overall (n = 165), 7.1% in females and 11.6% in males. Coinfection with M. genitalium occurred with another sexually-transmitted pathogen in 43 patients (18.3%), with C. trachomatis as the most common organism (n = 38). CONCLUSIONS: These data contribute to the evidence base for M. genitalium and STI screening in an active-duty military.

Automated dynamic motion correction using normalized gradient fields for 82rubidium PET myocardial blood flow quantification.

BACKGROUND: Patient motion can lead to misalignment of left ventricular (LV) volumes-of-interest (VOIs) and subsequently inaccurate quantification of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic PET myocardial perfusion images. We aimed to develop an image-based 3D-automated motion-correction algorithm that corrects the full dynamic sequence for translational motion, especially in the early blood phase frames (~ first minute) where the injected tracer activity is transitioning from the blood pool to the myocardium and where conventional image registration algorithms have had limited success. METHODS: We studied 225 consecutive patients who underwent dynamic rest/stress rubidium-82 chloride (82Rb) PET imaging. Dynamic image series consisting of 30 frames were reconstructed with frame durations ranging from 5 to 80 seconds. An automated algorithm localized the RV and LV blood pools in space and time and then registered each frame to a tissue reference image volume using normalized gradient fields with a modification of a signed distance function. The computed shifts and their global and regional flow estimates were compared to those of reference shifts that were assessed by three physician readers. RESULTS: The automated motion-correction shifts were within 5 mm of the manual motion-correction shifts across the entire sequence. The automated and manual motion-correction global MBF values had excellent linear agreement (R = 0.99, y = 0.97x + 0.06). Uncorrected flows outside of the limits of agreement with the manual motion-corrected flows were brought into agreement in 90% of the cases for global MBF and in 87% of the cases for global MFR. The limits of agreement for stress MBF were also reduced twofold globally and by fourfold in the RCA territory. CONCLUSIONS: An image-based, automated motion-correction algorithm for dynamic PET across the entire dynamic sequence using normalized gradient fields matched the results of manual motion correction in reducing bias and variance in MBF and MFR, particularly in the RCA territory.

The utility of 82Rb PET for myocardial viability assessment: Comparison with perfusion-metabolism 82Rb-18F-FDG PET.

BACKGROUND: 82Rb kinetics may distinguish scar from viable but dysfunctional (hibernating) myocardium. We sought to define the relationship between 82Rb kinetics and myocardial viability compared with conventional 82Rb and 18F-fluorodeoxyglucose (FDG) perfusion-metabolism PET imaging. METHODS: Consecutive patients (N = 120) referred for evaluation of myocardial viability prior to revascularization and normal volunteers (N = 37) were reviewed. Dynamic 82Rb 3D PET data were acquired at rest. 18F-FDG 3D PET data were acquired after metabolic preparation using a standardized hyperinsulinemic-euglycemic clamp. 82Rb kinetic parameters K1, k2, and partition coefficient (KP) were estimated by compartmental modeling RESULTS: Segmental 82Rb k2 and KP differed significantly between scarred and hibernating segments identified by Rb-FDG perfusion-metabolism (k2, 0.42 ± 0.25 vs. 0.22 ± 0.09 min-1; P < .0001; KP, 1.33 ± 0.62 vs. 2.25 ± 0.98 ml/g; P < .0001). As compared to Rb-FDG analysis, segmental Rb KP had a c-index, sensitivity and specificity of 0.809, 76% and 84%, respectively, for distinguishing hibernating and scarred segments. Segmental k2 performed similarly, but with lower specificity (75%, P < .001) CONCLUSIONS: In this pilot study, 82Rb kinetic parameters k2 and KP, which are readily estimated using a compartmental model commonly used for myocardial blood flow, reliably differentiated hibernating myocardium and scar. Further study is necessary to evaluate their clinical utility for predicting benefit after revascularization.

Blood pool and tissue phase patient motion effects on 82rubidium PET myocardial blood flow quantification.

BACKGROUND: Patient motion can lead to misalignment of left ventricular volumes of interest and subsequently inaccurate quantification of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic PET myocardial perfusion images. We aimed to identify the prevalence of patient motion in both blood and tissue phases and analyze the effects of this motion on MBF and MFR estimates. METHODS: We selected 225 consecutive patients that underwent dynamic stress/rest rubidium-82 chloride (82Rb) PET imaging. Dynamic image series were iteratively reconstructed with 5- to 10-second frame durations over the first 2 minutes for the blood phase and 10 to 80 seconds for the tissue phase. Motion shifts were assessed by 3 physician readers from the dynamic series and analyzed for frequency, magnitude, time, and direction of motion. The effects of this motion isolated in time, direction, and magnitude on global and regional MBF and MFR estimates were evaluated. Flow estimates derived from the motion corrected images were used as the error references. RESULTS: Mild to moderate motion (5-15 mm) was most prominent in the blood phase in 63% and 44% of the stress and rest studies, respectively. This motion was observed with frequencies of 75% in the septal and inferior directions for stress and 44% in the septal direction for rest. Images with blood phase isolated motion had mean global MBF and MFR errors of 2%-5%. Isolating blood phase motion in the inferior direction resulted in mean MBF and MFR errors of 29%-44% in the RCA territory. Flow errors due to tissue phase isolated motion were within 1%. CONCLUSIONS: Patient motion was most prevalent in the blood phase and MBF and MFR errors increased most substantially with motion in the inferior direction. Motion correction focused on these motions is needed to reduce MBF and MFR errors.

Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences.

Simian-human immunodeficiency virus (SHIV) challenge stocks are critical for preclinical testing of vaccines, antibodies, and other interventions aimed to prevent HIV-1. A major unmet need for the field has been the lack of a SHIV challenge stock expressing circulating recombinant form 01_AE (CRF01_AE) env sequences. We therefore sought to develop mucosally transmissible SHIV challenge stocks containing HIV-1 CRF01_AE env derived from acutely HIV-1 infected individuals from Thailand. SHIV-AE6, SHIV-AE6RM, and SHIV-AE16 contained env sequences that were >99% identical to the original HIV-1 isolate and did not require in vivo passaging. These viruses exhibited CCR5 tropism and displayed a tier 2 neutralization phenotype. These challenge stocks efficiently infected rhesus monkeys by the intrarectal route, replicated to high levels during acute infection, and established chronic viremia in a subset of animals. SHIV-AE16 was titrated for use in single, high dose as well as repetitive, low dose intrarectal challenge studies. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines, monoclonal antibodies, and other interventions targeted at preventing HIV-1 CRF01_AE infection.

Limitations of Rb-82 weight-adjusted dosing accuracy at low doses.

INTRODUCTION: Weight-adjusted dosing is important to maintain accurate quantification for dynamic cardiac three-dimensional positron emission tomography (PET). However, the manufacturer of the only Food and Drug Administration approved rubidium-82 (Rb-82) generator (CardioGen-82, Bracco Diagnostics, Inc.) recommends recalibration after each change in dose which is inefficient in a busy clinical PET lab. The objective of this study was to evaluate the accuracy of Rb-82 dosing without this recalibration. METHODS: After daily calibration to either 30 mCi (1110 MBq) or 12 mCi (444 MBq), Rb-82 doses between 6 and 45 mCi (222-1665 MBq) were eluted and measured on an external dose calibrator. This was repeated for four generators at weeks 1, 2, or 4 of the generator cycle. The measurements were compared with values reported by the infusion system. RESULTS: For requested doses less than 30 mCi, the measured dose was consistently lower than the requested dose, ranging from -3.2 mCi at 25 mCi to -5.5 mCi at 10 mCi. The error exceeded 10% for doses less than or equal to 26 mCi for the 30 mCi calibration. Residual activity in the infusion system dead volume accounted for the discrepancy between requested and delivered doses for calibration to 30 mCi but not 12 mCi. CONCLUSIONS: The CardioGen-82 infusion system is capable of accurate weight-adjusted doses without recalibration for Rb-82 doses as low as 26 mCi when calibrated to 30 mCi. For doses less than 26 mCi, the generator-reported residual activity within the infusion system can be used to correct the delivered dose.

Optimization of temporal sampling for 82rubidium PET myocardial blood flow quantification.

BACKGROUND: Suboptimal temporal sampling of left ventricular (LV) blood pool and tissue time-activity curves (TACs) may introduce bias and increased variability in estimates of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic PET myocardial perfusion images. We aimed to optimize temporal sampling for estimation of MBF and MFR. METHODS: Twenty-four normal volunteers and 32 patients underwent dynamic stress/rest rubidium-82 chloride (82Rb) PET imaging. Fine temporal sampling was used to estimate the full width at half maximum (FWHM) of the LV blood pool TAC. Fourier analysis was used to determine the longest sampling interval, T S, as a function of FWHM, which preserved the information content of the blood phase. Dynamic datasets were reconstructed with frame durations varying from 2 to 20 seconds over the first 2 minutes for the blood phase and 30 to 120 seconds for the tissue phase. The LV blood pool and tissue TACs were sampled using regions of interest (ROI) and fit to a compartment model for quantification of MBF and MFR. The effects of temporal sampling on MBF and MFR were evaluated using clinical data and simulations. RESULTS: T S increased linearly with input function FWHM (R = 0.93). Increasing the blood phase frame duration from 5 to 15 seconds resulted in MBF and MFR biases of 6-12% and increased variability of 14-24%. Frame durations <5 seconds had biases of less than 5% for both MBF and MFR values. Increasing the tissue phase frame durations from 30 to 120 seconds resulted in <5% biases. CONCLUSIONS: A two-phase framing of dynamic 82Rb PET images with frame durations of 5 seconds (blood phase) and 120 seconds (tissue phase) optimally samples the blood pool TAC for modern 3D PET systems.

Quiescent complement in nonhuman primates during E coli Shiga toxin-induced hemolytic uremic syndrome and thrombotic microangiopathy.

Enterohemorrhagic Escherichia coli (EHEC) produce ribosome-inactivating Shiga toxins (Stx1, Stx2) responsible for development of hemolytic uremic syndrome (HUS) and acute kidney injury (AKI). Some patients show complement activation during EHEC infection, raising the possibility of therapeutic targeting of complement for relief. Our juvenile nonhuman primate (Papio baboons) models of endotoxin-free Stx challenge exhibit full spectrum HUS, including thrombocytopenia, hemolytic anemia, and AKI with glomerular thrombotic microangiopathy. There were no significant increases in soluble terminal complement complex (C5b-9) levels after challenge with lethal Stx1 (n = 6) or Stx2 (n = 5) in plasma samples from T0 to euthanasia at 49.5 to 128 hours post-challenge. d-dimer and cell injury markers (HMGB1, histones) confirmed coagulopathy and cell injury. Thus, complement activation is not required for the development of thrombotic microangiopathy and HUS induced by EHEC Shiga toxins in these preclinical models, and benefits or risks of complement inhibition should be studied further for this infection.

Precision and accuracy of clinical quantification of myocardial blood flow by dynamic PET: A technical perspective.

A number of exciting advances in PET/CT technology and improvements in methodology have recently converged to enhance the feasibility of routine clinical quantification of myocardial blood flow and flow reserve. Recent promising clinical results are pointing toward an important role for myocardial blood flow in the care of patients. Absolute blood flow quantification can be a powerful clinical tool, but its utility will depend on maintaining precision and accuracy in the face of numerous potential sources of methodological errors. Here we review recent data and highlight the impact of PET instrumentation, image reconstruction, and quantification methods, and we emphasize (82)Rb cardiac PET which currently has the widest clinical application. It will be apparent that more data are needed, particularly in relation to newer PET technologies, as well as clinical standardization of PET protocols and methods. We provide recommendations for the methodological factors considered here. At present, myocardial flow reserve appears to be remarkably robust to various methodological errors; however, with greater attention to and more detailed understanding of these sources of error, the clinical benefits of stress-only blood flow measurement may eventually be more fully realized.

Effect of long-term isometric training on core/torso stiffness.

Although core stiffness enhances athletic performance traits, controversy exists regarding the effectiveness of isometric vs. dynamic core training methods. This study aimed to determine whether long-term changes in stiffness can be trained, and if so, what is the most effective method. Twenty-four healthy male subjects (23 ± 3 years; 1.8 ± 0.06 m; 77.5 ± 10.8 kg) were recruited for passive and active stiffness measurements before and after a 6-week core training intervention. Twelve subjects (22 ± 2 years; 1.8 ± 0.08 m; 78.3 ± 12.3 kg) were considered naive to physical and core exercise. The other 12 subjects (24 ± 3 years; 1.8 ± 0.05 m; 76.8 ± 9.7 kg) were Muay Thai athletes (savvy). A repeated-measures design compared core training methods (isometric vs. dynamic, with a control group) and subject training experience (naive vs. savvy) before and after a 6-week training period. Passive stiffness was assessed on a "frictionless" bending apparatus and active stiffness assessed through a quick release mechanism. Passive stiffness increased after the isometric training protocol. Dynamic training produced a smaller effect, and as expected, there was no change in the control group. Active stiffness did not change in any group. Comparisons between subject and training groups did not reveal any interactions. Thus, an isometric training approach was superior in terms of enhancing core stiffness. This is important since increased core stiffness enhances load bearing ability, arrests painful vertebral micromovements, and enhances ballistic distal limb movement. This may explain the efficacy reported for back and knee injury reduction.

Absolute myocardial flow quantification with (82)Rb PET/CT: comparison of different software packages and methods.

PURPOSE: In clinical cardiac (82)Rb PET, globally impaired coronary flow reserve (CFR) is a relevant marker for predicting short-term cardiovascular events. However, there are limited data on the impact of different software and methods for estimation of myocardial blood flow (MBF) and CFR. Our objective was to compare quantitative results obtained from previously validated software tools. METHODS: We retrospectively analyzed cardiac (82)Rb PET/CT data from 25 subjects (group 1, 62 ± 11 years) with low-to-intermediate probability of coronary artery disease (CAD) and 26 patients (group 2, 57 ± 10 years; P=0.07) with known CAD. Resting and vasodilator-stress MBF and CFR were derived using three software applications: (1) Corridor4DM (4DM) based on factor analysis (FA) and kinetic modeling, (2) 4DM based on region-of-interest (ROI) and kinetic modeling, (3) MunichHeart (MH), which uses a simplified ROI-based retention model approach, and (4) FlowQuant (FQ) based on ROI and compartmental modeling with constant distribution volume. RESULTS: Resting and stress MBF values (in milliliters per minute per gram) derived using the different methods were significantly different: using 4DM-FA, 4DM-ROI, FQ, and MH resting MBF values were 1.47 ± 0.59, 1.16 ± 0.51, 0.91 ± 0.39, and 0.90 ± 0.44, respectively (P<0.001), and stress MBF values were 3.05 ± 1.66, 2.26 ± 1.01, 1.90 ± 0.82, and 1.83 ± 0.81, respectively (P<0.001). However, there were no statistically significant differences among the CFR values (2.15 ± 1.08, 2.05 ± 0.83, 2.23 ± 0.89, and 2.21 ± 0.90, respectively; P=0.17). Regional MBF and CFR according to vascular territories showed similar results. Linear correlation coefficient for global CFR varied between 0.71 (MH vs. 4DM-ROI) and 0.90 (FQ vs. 4DM-ROI). Using a cut-off value of 2.0 for abnormal CFR, the agreement among the software programs ranged between 76 % (MH vs. FQ) and 90 % (FQ vs. 4DM-ROI). Interobserver agreement was in general excellent with all software packages. CONCLUSION: Quantitative assessment of resting and stress MBF with (82)Rb PET is dependent on the software and methods used, whereas CFR appears to be more comparable. Follow-up and treatment assessment should be done with the same software and method.

Role of Artificial Intelligence and Machine Learning to Create Predictors, Enhance Molecular Understanding, and Implement Purposeful Programs for Myocardial Recovery.

Heart failure (HF) affects millions of individuals and causes hundreds of thousands of deaths each year in the United States. Despite the public health burden, medical and device therapies for HF significantly improve clinical outcomes and, in a subset of patients, can cause reversal of abnormalities in cardiac structure and function, termed "myocardial recovery." By identifying novel patterns in high-dimensional data, artificial intelligence (AI) and machine learning (ML) algorithms can enhance the identification of key predictors and molecular drivers of myocardial recovery. Emerging research in the area has begun to demonstrate exciting results that could advance the standard of care. Although major obstacles remain to translate this technology to clinical practice, AI and ML hold the potential to usher in a new era of purposeful myocardial recovery programs based on precision medicine. In this review, we discuss applications of ML to the prediction of myocardial recovery, potential roles of ML in elucidating the mechanistic basis underlying recovery, barriers to the implementation of ML in clinical practice, and areas for future research.

Hospital costs and reimbursement for short-stay inpatient versus observation status hospitalizations for children with medical complexity.

BACKGROUND: There is a lack of uniformity across hospitals in applying inpatient versus observation status for short-stay (<48 h) pediatric hospitalizations, with negative financial implications associated with observation. Children with medical complexity (CMC) represent a growing population and incur high costs of care. The financial implications of inpatient and observation status for CMC have not been studied. OBJECTIVES: To compare costs and reimbursement for short-stay hospitalizations for CMC by inpatient and observation status, overall and stratified by payor. METHODS: We performed a cohort study of short-stay hospitalizations for CMC from 2016 to 2021 at 10 children's hospitals reporting reimbursement in the Pediatric Health Information System and Revenue Management Program. The primary outcome was the cost coverage ratio (CCR), defined as an encounter's reimbursement divided by the estimated cost. RESULTS: There were 89,282 encounters included. The median costs per encounter were similar across observation ($5206, IQR $3604-$7484) and inpatient ($6547, IQR $4725-$9349) encounters. For government payors, the median CCR was 0.6 (IQR 0.2-0.9) for observation encounters and 1.2 (IQR 0.8-1.9) for inpatient. For nongovernment payors, the median CCR was 1.6 (IQR 1.3-1.9) for observation and 1.6 (IQR 1.4-2) for inpatient. Government reimbursement was associated with increased risk for financial loss (OR 13.91, 95% CI 7.23, 26.77) and with a median net loss of $985,952 (IQR $389,871-$1,700,041) per hospital annually for observation encounters. CONCLUSIONS: Government-paid observation encounters for CMC are associated with significant financial loss at children's hospitals. This reimbursement model may pose a threat to children's hospitals' ability to care for CMC.

National cross-sectional study on cost consciousness, cost accuracy, and national medical waste reduction initiative knowledge among pediatric hospitalists in the United States.

BACKGROUND/OBJECTIVE: Despite initiatives to reduce waste and spending, there is a gap in physician knowledge regarding the cost of commonly ordered items. We examined the relationship between pediatric hospitalists' knowledge of national medical waste reduction initiatives, self-reported level of cost-consciousness (the degree in which cost affects practice), and cost accuracy (how close an estimate is to its hospital cost) at a national level. METHODS: This cross-sectional study used a national, online survey sent to hospitalists at 49 children's hospitals to assess their knowledge of national medical waste reduction initiatives, self-reported cost consciousness, and cost estimates for commonly ordered laboratory studies, medications, and imaging studies. Actual unit costs for each hospital were obtained from the Pediatric Health Information System (PHIS). Cost accuracy was calculated as the percent difference between each respondent's estimate and unit costs, using cost-charge ratios (CCR). RESULTS: The hospitalist response rate was 17.7% (327/1850), representing 40 hospitals. Overall, 33.1% of respondents had no knowledge of national medical waste reduction initiatives and 24.3% had no knowledge of local hospital costs. There was no significant relationship between cost accuracy and knowledge of national medical waste reduction initiatives or high self-reported cost consciousness. Hospitalists with the highest self-reported cost consciousness were the least accurate in estimating costs for commonly ordered laboratory studies, medications, or imaging studies. Respondents overestimated the cost of all items with the largest percent difference with medications. Hospitalists practicing over 15 years had the highest cost accuracy. CONCLUSIONS: A large proportion of pediatric hospitalists lack knowledge on national waste reduction initiatives. Improving the cost-accuracy of pediatric hospitalists may not reduce health care costs as they overestimated many hospital costs. Median unit cost lists could be a resource for educating medical students and residents about health care costs.

Mortality impact of low CAC density predominantly occurs in early atherosclerosis: explainable ML in the CAC consortium.

BACKGROUND: Machine learning (ML) models of risk prediction with coronary artery calcium (CAC) and CAC characteristics exhibit high performance, but are not inherently interpretable. OBJECTIVES: To determine the direction and magnitude of impact of CAC characteristics on 10-year all-cause mortality (ACM) with explainable ML. METHODS: We analyzed asymptomatic subjects in the CAC consortium. We trained ML models on 80% and tested on 20% of the data with XGBoost, using clinical characteristics â€‹+ â€‹CAC (ML 1) and additional CAC characteristics of CAC density and number of calcified vessels (ML 2). We applied SHAP, an explainable ML tool, to explore the relationship of CAC and CAC characteristics with 10-year all-cause and CV mortality. RESULTS: 2376 deaths occurred among 63,215 patients [68% male, median age 54 (IQR 47-61), CAC 3 (IQR 0-94.3)]. ML2 was similar to ML1 to predict all-cause mortality (Area Under the Curve (AUC) 0.819 vs 0.821, p â€‹= â€‹0.23), but superior for CV mortality (0.847 vs 0.845, p â€‹= â€‹0.03). Low CAC density increased mortality impact, particularly ≤0.75. Very low CAC density ≤0.75 was present in only 4.3% of the patients with measurable density, and 75% occurred in CAC1-100. The number of diseased vessels did not increase mortality overall when simultaneously accounting for CAC and CAC density. CONCLUSION: CAC density contributes to mortality risk primarily when it is very low ≤0.75, which is primarily observed in CAC 1-100. CAC and CAC density are more important for mortality prediction than the number of diseased vessels, and improve prediction of CV but not all-cause mortality. Explainable ML techniques are useful to describe granular relationships in otherwise opaque prediction models.

Trends in Pediatric Rhabdomyolysis and Associated Renal Failure: A 10-Year Population-Based Study.

OBJECTIVES: Rhabdomyolysis in children is a highly variable condition with presentations ranging from myalgias to more severe complications like acute renal failure. We sought to explore demographics and incidence of pediatric rhabdomyolysis hospitalizations and rates of associated renal failure, as our current understanding is limited. METHODS: This was a retrospective analysis using the Healthcare Cost and Utilization Project Kids' Inpatient Database to identify children hospitalized with a primary diagnosis of rhabdomyolysis. Data were analyzed for demographic characteristics, as well as geographic and temporal trends. Multivariable logistic regression was used to identify characteristics associated with rhabdomyolysis-associated acute renal failure. RESULTS: From 2006 to 2016, there were 8599 hospitalized children with a primary diagnosis of rhabdomyolysis. Overall, hospitalizations for pediatric rhabdomyolysis are increasing over time, with geographic peaks in the South and Northeast regions, and seasonal peaks in March and August. Though renal morbidity was diagnosed in 8.5% of children requiring hospitalization for rhabdomyolysis, very few of these patients required renal replacement therapy (0.41%), and death was rare (0.03%). Characteristics associated with renal failure included male sex, age greater than 15 years, and non-Hispanic Black race. CONCLUSIONS: Though renal failure occurs at a significant rate in children hospitalized with rhabdomyolysis, severe complications, including death, are rare. The number of children hospitalized with rhabdomyolysis varies by geographic region and month of the year. Future studies are needed to explore etiologies of rhabdomyolysis and laboratory values that predict higher risk of morbidity and mortality in children with rhabdomyolysis.

Hospital-Level Neighborhood Opportunity and Rehospitalization for Common Diagnoses at US Children's Hospitals.

OBJECTIVE: Neighborhood conditions influence child health outcomes, but data examining association between local factors and hospital utilization are lacking. We determined if hospitals' mix of patients by neighborhood opportunity correlates with rehospitalization for common diagnoses at US children's hospitals. METHODS: We analyzed all discharges in 2018 for children ≤18 years at 47 children's hospitals for 14 common diagnoses. The exposure was hospital-level mean neighborhood opportunity - measured by Child Opportunity Index (COI) - for each diagnosis. The outcome was same-cause rehospitalization within 365 days. We measured association via Pearson correlation coefficient. For diagnoses with significant associations, we also examined shorter rehospitalization time windows and compared unadjusted and COI-adjusted rehospitalization rates. RESULTS: There were 256,871 discharges included. Hospital-level COI ranged from 17th to 70th percentile nationally. Hospitals serving lower COI neighborhoods had more frequent rehospitalization for asthma (ρ -0.34 [95% confidence interval -0.57, -0.06]) and diabetes (ρ -0.33 [-0.56, -0.04]), but fewer primary mental health rehospitalizations (ρ 0.47 [0.21, 0.67]). There was no association for 11 other diagnoses. Secondary timepoint analysis revealed increasing correlation over time, with differences by diagnosis. Adjustment for hospital-level COI resulted in 26%, 32%, and 45% of hospitals changing >1 decile in rehospitalization rank order for diabetes, asthma, and mental health diagnoses, respectively. CONCLUSIONS: Children's hospitals vary widely in their mix of neighborhoods served. Asthma, diabetes, and mental health rehospitalization rates correlate with COI, suggesting that neighborhood factors may influence outcome disparities for these conditions. Hospital outcomes may be affected by neighborhood opportunity, which has implications for benchmarking.

Current and Future Applications of Artificial Intelligence in Coronary Artery Disease.

Cardiovascular diseases (CVDs) carry significant morbidity and mortality and are associated with substantial economic burden on healthcare systems around the world. Coronary artery disease, as one disease entity under the CVDs umbrella, had a prevalence of 7.2% among adults in the United States and incurred a financial burden of 360 billion US dollars in the years 2016-2017. The introduction of artificial intelligence (AI) and machine learning over the last two decades has unlocked new dimensions in the field of cardiovascular medicine. From automatic interpretations of heart rhythm disorders via smartwatches, to assisting in complex decision-making, AI has quickly expanded its realms in medicine and has demonstrated itself as a promising tool in helping clinicians guide treatment decisions. Understanding complex genetic interactions and developing clinical risk prediction models, advanced cardiac imaging, and improving mortality outcomes are just a few areas where AI has been applied in the domain of coronary artery disease. Through this review, we sought to summarize the advances in AI relating to coronary artery disease, current limitations, and future perspectives.