Search

Effective eradication of leukemic stem cells (LSCs) remains the greatest challenge in treating acute myeloid leukemia (AML). The immune receptor LAIR-1 has been shown to regulate LSC survival; however, the therapeutic potential of this pathway remains unexplored. We developed a therapeutic LAIR-1 agonist antibody, NC525, that induced cell death of LSCs, but not healthy hematopoietic stem cells in vitro, and killed LSCs and AML blasts in both cell- and patient-derived xenograft models. We showed that LAIR-1 agonism drives a unique apoptotic signaling program in leukemic cells that was enhanced in the presence of collagen. NC525 also significantly improved the activity of azacitidine and venetoclax to establish LAIR-1 targeting as a therapeutic strategy for AML that may synergize with standard-of-care therapies.

Gay, bisexual, and other men who have sex with men (MSM) have been disproportionately affected during the 2022 U.S. monkeypox outbreak, with Black or African American (Black) MSM being the most affected demographic group (1). As of September 28, 2022, Georgia had reported 1,784 monkeypox cases; 98% of which occurred in males and 77% among Black persons (2). As of September 13, 2022, 60% of reported cases were among persons with HIV infection, and 50% of persons with monkeypox had a sexually transmitted infection within the past year (3). Because of racial disparities in the incidence of monkeypox cases and a large proportion of cases among MSM in Georgia, early vaccination beginning in July focused on improving equitable access by establishing new and leveraging existing partnerships with community-based organizations that serve affected populations, including persons with HIV infection. Despite these efforts, disparities persisted because of high demand and limited vaccine supply. The Georgia Department of Public Health (DPH) requested CDC support for a vaccine pilot and received an additional allocation of 5,500 doses of JYNNEOS vaccine for administration at events leading up to and throughout a Black gay Pride festival in Atlanta, a multiday event held Labor Day weekend (September 2-5, 2022). The event celebrates lesbian, gay, bisexual, transgender, queer or questioning, intersex, asexual, and other (LGBTQIA+) communities of color and hosts more than 125,000 attendees each year. Before the festival (as of August 24), 17,546 persons had been vaccinated in Georgia, of whom 96% were male, 34% aged 25-36 years, 44% Black, and 8% Hispanic or Latino (Hispanic) (4). [ABSTRACT FROM AUTHOR]

With the continued increase in international travel and immigration to Georgia, the Department of Public Health (DPH) continued its mission to prevent and respond to Zika virus (ZIKV) transmission. Methods: We analyzed surveillance data from the DPH to compare the geographical distribution of counties conducting surveillance, total number, and overall percentage of mosquito species collected in 2016 and 2017. Mosquito surveillance in 2017 was mapped by county and species using ArcMap 10.2.0. Results: From 2016 and 2017, mosquito surveillance increased from 60 to 159 counties (165% increase). A total of 145,346 mosquitoes were trapped and identified in 2016 compared to 152,593 in 2017 (5.43% increase). There was a difference in the type of mosquito species found by year. Some species collected in previous years were not collected in 2017, while other species found in 2017 were not previously collected during mosquito surveillance. Also, certain mosquito species were found outside of their expected geographical range. Conclusion: The continued collaborative response to ZIKV by the DPH allowed a continued increase in its surveillance program. Existing and new partnerships continued to develop with military and local health departments to expand and share data. This additional surveillance data allowed DPH to make sound public health decisions regarding mosquito-borne disease risks and close gaps in data related to vector distribution. [ABSTRACT FROM AUTHOR]

Slipped Capital Femoral Epiphysis (SCFE) is a skeletal pathology affecting adolescents which requires timely surgery to prevent progression. Delays in diagnosis and treatment of SCFE can negatively affect patient prognosis, and few studies have examined how health disparities and barriers to care may influence these delays. In particular, only a handful of studies have included a Hispanic patient sample, despite this ethnic group's increased risk for the disease and unique barriers to care. A retrospective chart review was conducted for 124 patients surgically treated for idiopathic SCFE from January 2010 to September 2017. Patient data included age, facility and date of diagnosis, sex, BMI, race and ethnicity, Southwick slip angle, and insurance type. Results indicated that patients with private insurance were more likely to present with a mild slip than patients who were insured by Medicaid or uninsured, while patients without insurance were more likely to have severe slips. Patients without insurance also had a significantly higher mean slip than patients with insurance. The relationship between insurance status and slip angle degree was significant independent of race, even though Hispanic individuals were significantly more likely to have Medicaid or be uninsured. All patients without insurance, and a majority of those with Medicaid, were diagnosed in the emergency department. Time to diagnosis and slip angle were positively correlated, which suggests that longer delays led to increase of the slip angle, consistent with previous findings. Time to diagnosis and BMI were also correlated, which may be tied to socioeconomic factors, but the possibility of weight bias should not be dismissed. These results suggest that socioeconomic status and other factors may have contributed to barriers to care which led to delays in diagnosis and thus more severe slips. Future SCFE research should include health disparities variables to better inform treatment and prognosis.

Abstract Background Ankle syndesmosis injuries are common and range in severity from subclinical to grossly unstable. Definitive diagnosis of these injuries can be made with plain film radiographs, but are often missed when severity or image quality is low. Computed tomography (CT) and magnetic resonance imaging (MRI) can provide definitive diagnosis, but are costly and introduce the patient to radiation when CT is used. Ultrasonography may circumvent many of these disadvantages by being inexpensive, efficient, and able to detect injuries without radiation exposure. The purpose of this study was to evaluate the ability of ultrasonography to detect early stage supination-external rotation (SER) ankle syndesmosis injuries with a dynamic external rotational stress test. Methods Nine, all male, fresh frozen specimens were secured to an ankle rig and stress tested to 10 Nm of external rotational torque with ultrasonography at the tibiofibular clear space. The ankles were subjected to syndesmosis ligament sectioning and repeat stress measurements of the tibiofibular clear space at peak torque. Stress tests and measurements were repeated three times and averaged and analyzed using a repeated one-way analysis of variance (ANOVA). There were six ankle injury states examined including: Intact State, 75% of AITFL Cut, 100% of AITFL Cut, Fibula FX - Cut 8 cm proximal, 75% PITFL Cut, and 100% PITFL Cut. Results Dynamic external rotation stress evaluation using ultrasonography was able to detect a significant difference between the uninjured ankle with a tibiofibular clear space of 4.5 mm and the stage 1 complete injured ankle with a clear space of 6.0 mm (P

Background: This study investigates the association between the Geriatric Nutritional Risk Index (GNRI), a simple readily available measure of malnutrition risk, and 30-day postoperative complications following revision total shoulder arthroplasty (TSA)., Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who underwent TSA between 2015 and 2022. The study population was divided into three groups based on preoperative GNRI: normal/reference (GNRI > 98), moderate malnutrition (92 ≤ GNRI ≤ 98), and severe malnutrition (GNRI < 92). Logistic regression analysis was conducted to investigate the connection between preoperative GNRI and postoperative complications., Results: Compared to normal nutrition, moderate malnutrition was not independently associated with postoperative complications. Compared to normal nutrition, severe malnutrition was independently associated with a greater likelihood of experiencing any complication (odds ratio (OR) 3.08, 95% confidence interval (CI) 1.80-5.27; P  < 0.001), blood transfusions (OR 3.68, 95% CI 1.40-9.66; P  = 0.008), non-home discharge (OR 2.99, 95% CI 1.50-5.98; P  = 0.002), and length of stay >2 days (OR 3.10, 95% CI 1.77-5.42; P  < 0.001)., Discussion: Severe malnutrition based on GNRI is a predictor of early complications following revision TSA, however moderate malnutrition is not., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Immunotherapy has shown promise for treating patients with autoimmune diseases or cancer, yet treatment is associated with adverse effects associated with global activation or suppression of T cell immunity. Here, we developed antigen-presenting nanoparticles (APNs) to selectively engineer disease antigen (Ag)-specific T cells by in vivo mRNA delivery. APNs consist of a lipid nanoparticle core functionalized with peptide-major histocompatibility complexes (pMHCs), facilitating antigen-specific T cell transfection through cognate T cell receptor-mediated endocytosis. In mouse models of type 1 diabetes and multiple myeloma, APNs selectively deplete autoreactive T cells leading to durable control of glycemia, and engineer virus-specific T cells with anti-cancer chimeric antigen receptors (CARs), achieving comparable therapeutic outcome as virally transduced ex vivo CAR. Overall, our work supports the use of APNs to engineer disease-relevant T cells in vivo as Ag-specific immunotherapy for autoimmune disorders and cancer., Competing Interests: Competing Interests Statement G.A.K. is an equity shareholder of, and consults for, Sunbird Bio and Port Therapeutics. This study could affect his personal financial status. The terms of this arrangement have been reviewed and approved by Georgia Tech in accordance with its conflict-of-interest policies. F.Y.S., J.C.S., C.S.C. and G.A.K. are listed as inventors on patent applications pertaining to the results of the paper.

Background: There is a paucity of information around whether hospital length of stay and readmission rates differ based upon hospital type for adolescents and young adults (AYA) with complex chronic diseases (CCDs)., Objective: To measure the association between hospital type and readmission rates and index admission LOS among AYA with CCDs., Methods: We performed a retrospective cross-sectional study of 2017 Healthcare Cost and Utilization Project State Inpatient Databases, including patients 12-25 years old with cystic fibrosis (CF), sickle cell disease (SCD), spina bifida (SB), inflammatory bowel disease (IBD), and diabetes mellitus (DM). Index hospitalizations were categorized by hospital type (pediatric hospitals [PHs], adult hospitals with pediatric services [AHPSs], and adult hospitals without pediatric services [AHs]), CCD, and age group. We compared case-mix adjusted 30-day readmission rates and differences in index admission LOS between hospital types., Results: Adult hospitals without pediatric services exhibited higher readmission rates (25.4%) than AHPS (22.9%) and PH (15.1%). Compared to patients with CF admitted to AH, lower readmission rates were associated with longer LOS at both AHPS (relative ratio [RR]: 1.25, 95% confidence interval [CI]: 1.02-1.55) and PH (RR: 1.59, 95% CI: 1.28-1.97). Patients with DM admitted to AHPS (odds ratio [OR]: 0.75, 95% CI: 0.62-0.91) and PH (OR: 0.47, 95% CI: 0.31-0.71) also demonstrated lower readmission rates than those admitted to AH., Conclusions: For AYA with CCD, hospital type is associated with differences in readmission rates and LOS. Lower readmission rates at hospitals with pediatric services compared to adult hospitals without pediatric services suggest hospital type has a significant impact on outcomes., (© 2024 Society of Hospital Medicine.)

Background and Objective: Few studies have explored the relationship between social drivers of health and pediatric low-value care (LVC). We assessed the relationship between Childhood Opportunity Index (COI) 2.0 and LVC in children's hospitals., Methods: We applied the Pediatric Health Information System LVC Calculator to emergency and inpatient encounters from July 2021 through June 2022. Proportions with LVC in highest (greatest opportunity) and lowest COI quintiles were compared. Generalized estimating equation logistic regression models were used to analyze LVC trends across COI quintiles., Results: 842 463 encounters were eligible for 20 LVC measures. Across all measures, odds of LVC increased across increasing COI quintiles (adjusted odds ratio [OR] 1.06, 95% confidence interval [CI] 1.03-1.08). For 12 measures, LVC was proportionally more common in highest versus lowest COI quintile, whereas the reverse was true for 4. Regression modeling revealed increasing LVC as COI increased across all quintiles for 10 measures; gastric acid suppression for infants had the strongest association (OR 1.22, 95% CI 1.17-1.27). Three measures revealed decreasing LVC across increasing COI quintiles; Group A streptococcal testing among children <3 years revealed the lowest OR (0.85, 95% CI 0.73-0.99). The absolute volume of LVC delivered was greatest among low COI quintiles for most measures., Conclusions: Likelihood of LVC increased across COI quintiles for 10 of 20 measures, whereas 3 measures revealed reverse trends. High volumes of LVC across quintiles support a need for broad de-implementation efforts; measures with greater impact on children with lower opportunity warrant prioritized efforts., (Copyright © 2024 by the American Academy of Pediatrics.)

Purpose: Procalcitonin (PCT) levels may play a role in decreasing the duration of antimicrobial therapy in institutions that have long durations of therapy for management of community-acquired pneumonia. We assessed the impact of the combination of pharmacist stewardship interventions assisted by a clinical decision support (CDS) tool and PCT assessment on the antimicrobial days of therapy (DOT) prescribed for respiratory tract infections (RTIs)., Methods: We conducted a quasi-experimental study in which patients in the preintervention group were admitted between April and June 2021 and patients in the intervention group were admitted between April and June 2022. In the intervention phase, a CDS tool was utilized to alert clinical pharmacists when patients met specific criteria. This alert was programmed to activate for individual patients when a reported PCT level was less than 0.25 ng/mL and the patient was on antimicrobials prescribed for an RTI as indicated by providers in the electronic health record. Stewardship interventions were made by pharmacists via prospective audit and feedback. The primary endpoint was inpatient antimicrobial DOT for RTIs., Results: There were 90 patients in the preintervention group and 104 patients in the intervention group. Although baseline characteristics were not well matched between the groups, favoring the preintervention group, the median DOT was lower in the intervention group, at 3 days (interquartile range [IQR], 2-4 days), compared to 4 days (IQR, 2.8-5 days) in the preintervention group (P = 0.001)., Conclusion: The results of our study demonstrate the utility of pharmacist interventions coupled with CDS and PCT in reducing antimicrobial DOT prescribed for RTIs. Antimicrobial stewardship programs may benefit from implementing a PCT bundle., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: The aim of this study is to explore potential complications and risk factors associated with revision TSA in patients with congestive heart failure (CHF)., Methods: This study examined all individuals who underwent revision total shoulder arthroplasty (TSA) from 2015 to 2022, sourced from the American College of Surgeons National Surgical Quality Improvement database. The analysis encompassed patient demographics, comorbidities, and 30-day postoperative complications. Logistic regression was employed to analyze the postoperative complications linked to patients with preoperative CHF., Results: Compared to patients without CHF, patients with CHF were significantly associated with dependent functional status (P < .001), chronic obstructive pulmonary disease (P < .001), and hypertension (P = .002). Compared to patients without CHF, patients with CHF were independently associated with a significantly greater likelihood of experiencing any complication (OR 2.19, 95% CI 1.12-4.29; P = .022) and non-home discharge (OR 3.02, 95% CI 1.37-6.65; P = .006)., Conclusion: Congestive heart failure was identified as an independent risk factor for experiencing any complication and non-home discharge in patients undergoing revision TSA. Awareness of the cardiovascular health status of a patient and its severity can influence the decision-making process when considering revision TSA., Level of Evidence Iii: Retrospective Cohort Comparison Using Large Database; Prognosis Study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively., Methods: We studied healthy older adult participants ( N  = 21, ages 48-79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task., Results: Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation., Conclusions: The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way.

Competing Interests: This work received funding from iotaMotion, Inc. M.R.H. is a cofounder and director of iotaMotion; B.J.G. serves as consultant for iotaMotion, Inc. For the remaining authors, there are no conflicts of interest to report.

Objectives: Teaching ultrasound imaging is on the rise in undergraduate medical anatomy education. However, there is little research exploring the use of ultrasound in preparatory graduate programs. The purpose of this study is to identify the effects of ultrasound imaging inclusion in a graduate gross anatomy course., Methods: Master of Medical Sciences students were enrolled in a prosection-based anatomy course that included pinned cadaver stations and an ultrasound station. Using ultrasound, teaching assistants imaged volunteers demonstrating anatomical structures students previously learned at cadaver stations. Students answered one ultrasound image question on each practical exam and were asked to participate in a pre- and post-course survey. Student practical and lecture exam scores and final course grades from the 2022 cohort were compared to a historical control cohort from 2021 via statistical analysis, including a survey administered to the 2022 cohort., Results: Two hundred students from the 2021 cohort and 164 students from the 2022 cohort participated in this study. Students in the 2022 cohort had significantly higher scores in 1 of the 5 practical exams (P < .05, d = .289), and 2 of the 5 written exams (P < .05, d = .207), (P < .05, d = .311). Survey data revealed increased (P < .05, d = 1.203) learning outcome achievement from pre-survey to post-survey in the intervention cohort. Students who correctly answered the ultrasound question performed significantly better on practical's 3 (P < .05) and 4 (P < .05) than those who missed the ultrasound question., Conclusions: These findings suggest that ultrasound imaging in a cadaver lab is beneficial to graduate students' learning and understanding of gross anatomy., (© 2024 The Authors. Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)

This study evaluates intracochlear electrocochleography (ECochG) for real-time monitoring during cochlear implantation. One aim tested whether adjusting the recording electrode site would help differentiate between atraumatic and traumatic ECochG amplitude decrements. A second aim assessed whether associations between ECochG amplitude decrements and post-operative hearing loss were weaker when considering hearing sensitivity at the ECochG stimulus frequency compared to a broader frequency range. Eleven adult cochlear implant recipients who were candidates for electro-acoustic stimulation participated. Single-frequency (500-Hz) ECochG was performed during cochlear implantation; the amplitude of the first harmonic of the difference waveform was considered. Post-operative hearing preservation at 500 Hz ranged from 0 to 94%. The expected relationship between ECochG amplitude decrements and hearing preservation was observed, though the trend was not statistically significant, and predictions were grossly inaccurate for two participants. Associations did not improve when considering alternative recording sites or hearing sensitivity two octaves above the ECochG stimulus frequency. Intracochlear location of a moving recording electrode is a known confound to real-time interpretation of ECochG amplitude fluctuations, which was illustrated by the strength of the correlation with ECochG amplitude decrements. Multiple factors contribute to ECochG amplitude patterns and to hearing preservation; these results highlight the confounding influence of intracochlear recording electrode location on the ECochG.

Background: The 2022 global mpox outbreak was notable for transmission between persons outside of travel and zoonotic exposures and primarily through intimate contact. An understanding of the presentation of mpox in people with human immunodeficiency virus (HIV) and other immunocompromising conditions and knowledge of the efficacy of tecovirimat continue to evolve., Methods: This retrospective study describes clinical features and outcomes of persons with mpox who received tecovirimat. Data were obtained via medical record review of patients prescribed tecovirimat in a health system in New York City during the height of the outbreak in 2022., Results: One hundred thirty people received tecovirimat between 1 July and 1 October 2022. People with HIV (n = 80) experienced similar rates of recovery, bacterial superinfections, and hospitalization compared to patients without immunocompromising conditions. Individuals determined to be severely immunocompromised (n = 14) had a higher risk of hospitalization than those without severe immunocompromise (cohort inclusive of those with well-controlled HIV, excluding those without virologic suppression, n = 101): 50% versus 9% ( P < .001). Hospitalized patients (n = 18 [13% of total]) were primarily admitted for bacterial superinfections (44.4%), with a median hospital stay of 4 days. Of those who completed follow-up (n = 85 [66%]), 97% had recovery of lesions at time of posttreatment assessment. Tecovirimat was well tolerated; there were no reported severe adverse events attributed to therapy., Conclusions: There were no significant differences in outcomes between people with HIV when evaluated as a whole and patients without immunocompromising conditions. However, mpox infection was associated with higher rates of hospitalization in those with severe immunocompromise, including patients with HIV/AIDS. Treatment with tecovirimat was well tolerated.Key Points: In our mpox cohort, people with HIV had similar rates of recovery and complications as those without HIV or other immunocompromising conditions. Severe immunocompromise was associated with a higher hospitalization rate. Tecovirimat was well tolerated, with minimal side effects., Competing Interests: Potential conflicts of interest. All authors had access to prescribe tecovirimat based on the CDC EA-IND protocol and local IRB approval. L. L. and G. P. are co-investigators on STOMP, and J. A. is the site principal investigator for the STOMP trial at the Icahn School of Medicine at Mount Sinai. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Child Opportunity Index (COI) measures neighborhood contextual factors (education, health and environment, social and economic) that may influence child health. Such factors have been associated with hospitalizations for ambulatory care sensitive conditions (ACSC). Lower COI has been associated with higher health care utilization, yet association with rehospitalization(s) for ACSC remains unknown. Our objective is to determine the association between COI and ACSC rehospitalizations., Methods: Multicenter retrospective cohort study of children ages 0 to 17 years with a hospital admission for ambulatory care sensitive conditions in 2017 or 2018. Exposure was COI. Outcome was rehospitalization within 1 year of index admission (analyzed as any or ≥2 rehospitalization) for ACSC. Logistic regression models adjusted for age, sex, severity, and complex and mental health conditions., Results: The study included 184 478 children. Of hospitalizations, 28.3% were by children from very low COI and 16.5% were by children from very high COI neighborhoods. In risk-adjusted models, ACSC rehospitalization was higher for children from very low COI than very high COI neighborhoods; any rehospitalization occurred for 18.7% from very low COI and 13.5% from very high COI neighborhoods (adjusted odds ratio 1.14 [1.05-1.23]), whereas ≥2 rehospitalization occurred for 4.8% from very low COI and 3.2% from very high COI neighborhoods (odds ratio 1.51 [1.29-1.75])., Conclusions: Children from neighborhoods with low COI had higher rehospitalizations for ACSCs. Further research is needed to understand how hospital systems can address social determinants of health in the communities they serve to prevent rehospitalizations., (Copyright © 2023 by the American Academy of Pediatrics.)

Objective: Incorporating diversity, equity, inclusion, and anti-racism principles into clinical and didactic education is essential because each influence cognitive and affective attitudes in pharmacy practice. Educators must learn from the past to enlighten the future. For example, race is a social construct, not a biological construct. However, it persistently acts as a surrogate for determining medical diagnoses and treatment., Findings: Precision medicine and pharmacogenomics can serve as a basis for deconstructing social constructs surrounding race and other social determinants of health., Summary: In this review, the authors highlight why using race in health education will lead to less-than-optimal clinical decisions and discuss best practices for incorporating diversity, equity, inclusion, and anti-racism into health education from a pharmacogenomic-based perspective., Competing Interests: Declaration of Competing Interests None declared., (Copyright © 2023 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

Objective: Reducing pediatric readmissions has become a national priority; however, the use of readmission rates as a quality metric remains controversial. The goal of this study was to examine short-term stability and long-term changes in hospital readmission rates., Methods: Data from the Pediatric Health Information System were used to compare annual 30-day risk-adjusted readmission rates (RARRs) in 47 US children's hospitals from 2016 to 2017 (short-term) and 2016 to 2019 (long-term). Pearson correlation coefficients and weighted Cohen's Kappa statistics were used to measure correlation and agreement across years for hospital-level RARRs and performance quartiles., Results: Median (IQR) 30-day RARRs remained stable from 7.7% (7.0-8.3) in 2016 to 7.6% (7.0-8.1) in 2019. Individual hospital RARRs in 2016 were strongly correlated with the same hospital's 2017 rate (R 2  = 0.89 [95% confidence interval (CI) 0.80-0.94]) and moderately correlated with those in 2019 (R 2  = 0.49 [95%CI 0.23-0.68]). Short-term RARRs (2016 vs 2017) were more highly correlated for medical conditions than surgical conditions, but correlations between long-term medical and surgical RARRs (2016 vs 2019) were similar. Agreement between RARRs was higher when comparing short-term changes (0.73 [95%CI 0.59-0.86]) than long-term changes (0.45 [95%CI 0.27-0.63]). From 2016 to 2019, RARRs increased by ≥1% in 7 (15%) hospitals and decreased by ≥1% in 6 (13%) hospitals. Only 7 (15%) hospitals experienced reductions in RARRs over the short and long-term., Conclusions: Hospital-level performance on RARRs remained stable with high agreement over the short-term suggesting stability of readmission measures. There was little evidence of sustained improvement in hospital-level performance over multiple years., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Low intensity, transcranial focused ultrasound (tFUS) is a re-emerging brain stimulation technique with the unique capability of reaching deep brain structures non-invasively., Objective/hypothesis: We sought to demonstrate that tFUS can selectively and accurately target and modulate deep brain structures in humans important for emotional functioning as well as learning and memory. We hypothesized that tFUS would result in significant longitudinal changes in perfusion in the targeted brain region as well as selective modulation of BOLD activity and BOLD-based functional connectivity of the target region., Methods: In this study, we collected MRI before, simultaneously during, and after tFUS of two deep brain structures on different days in sixteen healthy adults each serving as their own control. Using longitudinal arterial spin labeling (ASL) MRI and simultaneous blood oxygen level dependent (BOLD) functional MRI, we found changes in cerebral perfusion, regional brain activity and functional connectivity specific to the targeted regions of the amygdala and entorhinal cortex (ErC)., Results: tFUS selectively increased perfusion in the targeted brain region and not in the contralateral homolog or either bilateral control region. Additionally, tFUS directly affected BOLD activity in a target specific fashion without engaging auditory cortex in any analysis. Finally, tFUS resulted in selective modulation of the targeted functional network connectivity., Conclusion: We demonstrate that tFUS can selectively modulate perfusion, neural activity and connectivity in deep brain structures and connected networks. Lack of auditory cortex findings suggests that the mechanism of tFUS action is not due to auditory or acoustic startle response but rather a direct neuromodulatory process. Our findings suggest that tFUS has the potential for future application as a novel therapy in a wide range of neurological and psychiatric disorders associated with subcortical pathology., Competing Interests: NSu was a consultant for BrainSonix Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kuhn, Spivak, Dang, Becerra, Halavi, Rotstein, Rosenberg, Hiller, Swenson, Cvijanovic, Dang, Sun, Kronemyer, Berlow, Revett, Suthana, Monti and Bookheimer.)

Visualizing the presence and distribution of multiple specific molecular markers within a tumor can reveal the composition of its microenvironment, inform diagnosis, stratify patients, and guide treatment. Raman imaging with multiple molecularly-targeted surface enhanced Raman scattering (SERS) nanoprobes could help investigate emerging cancer treatments preclinically or enable personalized treatment assessment. Here, we report a comprehensive strategy for multiplexed imaging using SERS nanoprobes and machine learning (ML) to monitor the early effects of immune checkpoint blockade (ICB) in tumor-bearing mice. We used antibody-functionalized SERS nanoprobes to visualize 7 + 1 immunotherapy-related targets simultaneously. The multiplexed images were spectrally resolved and then spatially segmented into superpixels based on the unmixed signals. The superpixels were used to train ML models, leading to the successful classification of mice into treated and untreated groups, and identifying tumor regions with variable responses to treatment. This method may help predict treatment efficacy in tumors and identify areas of tumor variability and therapy resistance.

Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut and immunohistochemically (IHC) stained for Ki67 (MIB-1 antibody). The QuPath platform was used to evaluate tumoral Ki67 expression. Calibration of the DIA method was performed as in published studies. A guideline for building an automated Ki67 scoring algorithm was sent to participating labs. Very high correlation and no systematic error (p = 0.08) was found between consecutive Ki67 IHC sections. Ki67 scores were higher for core biopsy slides compared to paired whole sections from resections (p ≤ 0.001; median difference: 5.31%). The systematic discrepancy between core biopsy and corresponding whole sections was likely due to pre-analytical factors (tissue handling, fixation). Therefore, Ki67 IHC should be tested on core biopsy samples to best reflect the biological status of the tumor., (© 2022. The Author(s).)

We propose and demonstrate a scheme for Doppler compensated optical cavity enhancement of atom interferometers at significantly increased mode diameters. This overcomes the primary limitations in cavity enhancement for atom interferometry, circumventing the cavity linewidth limit and enabling spatial mode filtering, power enhancement, and a large beam diameter simultaneously. This approach combines a magnified linear cavity with an intracavity Pockels cell. The Pockels cell induces a voltage-controlled birefringence allowing the cavity mode frequencies to follow the Raman lasers as they track gravitationally induced Doppler shifts, removing the dominant limitation of current cavity enhanced systems. A cavity is built to this geometry and shown to simultaneously realise Doppler compensation, a 5.8 ± 0.15 mm1/e 2 diameter beam waist and an enhancement factor of >5× at a finesse of 35. Tuneable Gouy phase enables the suppression of higher order spatial modes and the avoidance of regions of instability. Atom interferometers will see increased contrast at extended interferometry times along with power enhancement and the reduction of optical aberrations. This is relevant to power constrained applications in quantum technology, alongside the absolute performance requirements of fundamental science.

Objective: Despite extensive efforts, overall readmission rates at US children's hospitals have not materially declined over the past decade, raising questions about how to direct future efforts. Using measures of prevalence and performance variation we describe readmission rates by condition and identify priority conditions for future intervention., Methods: Retrospective cohort study of 49 US children's hospitals in the Pediatric Health Information System in 2017. Conditions were classified using All Patients Refined Diagnosis Related Groups. 30-day unadjusted and risk-adjusted readmission rates were calculated for each hospital/condition using the Pediatric All Cause Readmission measure. We ranked the highest volume conditions by rate variation (RV, interquartile range divided by the median) for each condition across hospitals., Results: The sample included 811,434 index hospitalizations with 50,196 (6.2%) 30-day readmissions. The RV across hospitals/conditions was between 0 and 2.8 (median = 0.7). Common reasons for admission had low RVs across hospitals, for example, bronchiolitis (readmission rate = 5.6%, RV = 0.4), seizure (readmission rate = 6.6%, RV = 0.3), and asthma (readmission rate = 3.1%, RV = 0.4). We identified 33 conditions with high variation in readmission rates across hospitals, which accounted for 18% of all discharges and 11% of all pediatric readmissions. These conditions may serve as candidates for future readmission reduction activities., Conclusions: Many common childhood conditions have little variation in readmission rates across children's hospitals, suggesting limited future improvement opportunities. Conditions with high rate variation may provide opportunities for quality improvement; however, these conditions account for a relatively small share of total discharges suggesting modest potential impacts on national rates., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Observation status (OBS) stays incur similar costs to low-acuity, short-stay inpatient (IP) hospitalizations. Despite this, payment for OBS is likely less and may represent a financial liability for children's hospitals. Thus, we described the financial outcomes associated with OBS stays compared to similar IP stays by hospital and payer., Methods: We conducted a retrospective cohort study of clinically similar pediatric OBS and IP encounters at 15 hospitals contributing to the revenue management program in 2017. Clinical and demographic characteristics were described. For each hospitalization, the cost coverage ratio (CCR) was calculated by dividing revenue by estimated cost of hospitalization. Differences in CCR were evaluated using Wilcoxon rank sum tests and results were stratified by billing designation and payer. CCR for OBS and IP stays were compared by institution, and the estimated increase in revenue by billing OBS stays as IP was calculated., Results: OBS was assigned to 70 981 (56.9%) of 124 789 hospitalizations. Use of OBS varied across hospitals (8%-86%). For included hospitalizations, OBS stays were more likely than IP stays to result in financial loss (57.0% vs 35.7%). OBS stays paid by public payer had the lowest median CCR (0.6; interquartile range [IQR], 0.2-0.9). Paying OBS stays at the median IP rates would have increased revenue by $167 million across the 15 hospitals., Conclusions: OBS stays were significantly more likely to result in poor financial outcomes than similar IP stays. Costs of hospitalization and billing designations are poorly aligned and represent an opportunity for children's hospitals and payers to restructure payment models., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no conflicts of interest relevant to this article to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

Left ventricular assist devices (LVADs) provide circulatory support to patients with severe left ventricular systolic dysfunction. Many such patients have a pre-existing implantable cardioverter-defibrillator (ICD) at the time of their LVAD surgery. LVAD implantation can alter the ICD lead parameters, including R-wave sensing, right ventricular capture threshold, and impedance. These changes can in turn affect the ability of the ICD to successfully treat malignant ventricular arrhythmias. In most patients who present with ineffective ICD shocks, the failed shock is assumed to be secondary to the patient's severe cardiomyopathy. Especially, the role of physical examination in such patients is often minimized. In our patient, a thorough history-taking and history-guided physical examination led us to the root cause of the failed ICD shocks. Our patient was noted to have a metal tongue piercing, which was the likely cause of his ineffective ICD shocks. Our case highlights the importance of a comprehensive history-taking and physical examination., Competing Interests: Dr. Worley receives royalties from Pressure Products and Merit Medical. The other authors report no conflicts of interest for the published content., (Copyright: © 2021 Innovations in Cardiac Rhythm Management.)

The development of a massively parallel lithographic technique called electrochemical polymer pen lithography is reported. Pyramidal pen arrays, consisting of more than 10 000 hydrogel pens loaded with metal salts, are integrated into a three-electrode cell and used to locally reduce ions at each pen tip. This system enables high-throughput patterning of a variety of metallic inks (e.g., Ni 2+ , Pt 2+ , Ag + ) on the nanometer to micrometer length scale. By incorporating a z-direction piezo actuator, the extension length and dwell time can be used to precisely define feature dimensions (210 to 10 µm in width, and up to 900 nm in height, thus far). Furthermore, by controlling the potential and precursor concentrations, more than one element can be simultaneously deposited, creating a new tool for the synthesis of alloy features, such as NiCo, which are relevant for catalysis. Importantly, this methodology enables fine control over feature size and composition in a single pattern, which may make it ultimately useful for rapid, high-throughput combinatorial screening of metallic features., (© 2021 Wiley-VCH GmbH.)

Background: High costs associated with hospitalization have encouraged reductions in unnecessary encounters. A subset of observation status patients receive minimal interventions and incur low use costs. These patients may contain a cohort that could safely be treated outside of the hospital. Thus, we sought to describe characteristics of low resource use (LRU) observation status hospitalizations and variation in LRU stays across hospitals., Methods: We conducted a retrospective cohort study of pediatric observation encounters at 42 hospitals contributing to the Pediatric Health Information System database from January 1, 2019, to December 31, 2019. For each hospitalization, we calculated the use ratio (nonroom costs to total hospitalization cost). We grouped stays into use quartiles with the lowest labeled LRU. We described associations with LRU stays and performed classification and regression tree analyses to identify the combination of characteristics most associated with LRU. Finally, we described the proportion of LRU hospitalizations across hospitals., Results: We identified 174 315 observation encounters (44 422 LRU). Children <1 year (odds ratio [OR] 3.3; 95% confidence interval [CI] 3.1-3.4), without complex chronic conditions (OR 3.6; 95% CI 3.2-4.0), and those directly admitted (OR 4.2; 95% CI 4.1-4.4) had the greatest odds of experiencing an LRU encounter. Those children with the combination of direct admission, no medical complexity, and a respiratory diagnosis experienced an LRU stay 69.5% of the time. We observed variation in LRU encounters (1%-57% of observation encounters) across hospitals., Conclusions: LRU observation encounters are variable across children's hospitals. These stays may include a cohort of patients who could be treated outside of the hospital., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Children's hospitals responded to COVID-19 by limiting nonurgent healthcare encounters, conserving personal protective equipment, and restructuring care processes to mitigate viral spread. We assessed year-over-year trends in healthcare encounters and hospital charges across US children's hospitals before and during the COVID-19 pandemic. We performed a retrospective analysis, comparing healthcare encounters and inflation-adjusted charges from 26 tertiary children's hospitals reporting to the PROSPECT database from February 1 to June 30 in 2019 (before the COVID-19 pandemic) and 2020 (during the COVID-19 pandemic). All children's hospitals experienced similar trends in healthcare encounters and charges during the study period. Inpatient bed-days, emergency department visits, and surgeries were lower by a median 36%, 65%, and 77%, respectively, per hospital by the week of April 15 (the nadir) in 2020 compared with 2019. Across the study period in 2020, children's hospitals experienced a median decrease of $276 million in charges.

Background and Objectives: Length of stay (LOS) is a common benchmarking measure for hospital resource use and quality. Observation status (OBS) is considered an outpatient service despite the use of the same facilities as inpatient status (IP) in most children's hospitals, and LOS calculations often exclude OBS stays. Variability in the use of OBS by hospitals may significantly impact calculated LOS. We sought to determine the impact of including OBS in calculating LOS across children's hospitals., Methods: Retrospective cohort study of hospitalized children (age <19 years) in 2017 from the Pediatric Health Information System (Children's Hospital Association, Lenexa, KS). Normal newborns, transfers, deaths, and hospitals not reporting LOS in hours were excluded. Risk-adjusted geometric mean length of stay (RA-LOS) for IP-only and IP plus OBS was calculated and each hospital was ranked by quintile., Results: In 2017, 45 hospitals and 625 032 hospitalizations met inclusion criteria (IP = 410 731 [65.7%], OBS = 214 301 [34.3%]). Across hospitals, OBS represented 0.0% to 60.3% of total discharges. The RA-LOS (SD) in hours for IP and IP plus OBS was 75.2 (2.6) and 54.3 (2.7), respectively ( P < .001). For hospitals reporting OBS, the addition of OBS to IP RA-LOS calculations resulted in a decrease in RA-LOS compared with IP encounters alone. Three-fourths of hospitals changed ≥1 quintile in LOS ranking with the inclusion of OBS., Conclusions: Children's hospitals exhibit significant variability in the assignment of OBS to hospitalized patients and inclusion of OBS significantly impacts RA-LOS calculations. Careful consideration should be given to the inclusion of OBS when determining RA-LOS for benchmarking, quality and resource use measurements., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Objectives: Pediatric emergency department (ED) patients are at an increased risk for experiencing a preventable medication error. Studies show that pharmacists are effective at decreasing medication errors on inpatient orders but there are few studies looking at error reduction on discharge prescriptions. Children's Health implemented a prospective pharmacist verification process on all ED discharge prescriptions. The objective of this study is to identify and describe the prescription errors leaving a pediatric ED after the implementation of this pharmacist review process., Methods: An electronic medical database was utilized to identify all ED prescriptions between January 1, 2016, and June 30, 2016. A random number generator was used to select 750 prescriptions. Two pharmacists independently performed a chart review assessing prescriptions for errors. A third pharmacist was used to clarify discordant assessments between the 2 pharmacists. Errors were recorded and assessed for severity using the Taylor et al 2005 stratification. The primary objective of this study is to identify the errors leaving the ED. Secondary objectives include: error severity, error subtype, and readmission rates., Results: Forty-one errors were identified from 750 randomly selected prescriptions for a total error rate of 5.5%. The most common subtypes of errors were missing duration (39%) and antimicrobial optimization (24.4%). When using the Taylor et al 2005 scale, no prescriptions were classified as severe or serious. None of the errors led to patient harm.

Intravenous (IV) magnesium is used as an adjunct therapy in management of status asthmaticus with a goal of reducing intubation rate. A recent review suggests that IV magnesium use in status asthmaticus reduces admission rates. This is contrary to the observation of practicing emergency room physicians. The goal of this study was to assess trends in IV magnesium use for status asthmaticus in US children's hospitals over 8 years through a retrospective analysis of children younger than 18 years using the Pediatric Health Information System database. Outcomes were IV magnesium use, inpatient and intensive care unit admission rate, geometric mean length of stay, and 7-day all-cause readmission rate. IV magnesium use for asthma hospitalization more than doubled over 8 years (17% vs. 36%; P < .001). Yearly trends were not significantly associated with hospital or intensive care unit admission rate or 7-day all-cause readmissions, although length of stay was reduced (P < .001).

To personalize treatment for renal cell carcinoma (RCC), it would be ideal to confirm the activity of druggable protein pathways within individual tumors. We have developed a high-resolution nanoimmunoassay (NIA) to measure protein activity with high precision in scant specimens (eg, fine needle aspirates [FNAs]). Here, we used NIA to determine whether protein activation varied in different regions of RCC tumors. Since most RCC therapies target angiogenesis by inhibiting the vascular endothelial growth factor (VEGF) receptor, we quantified phosphorylation of extracellular signal-regulated kinase (ERK), a downstream effector of the VEGF signaling pathway. In 90 ex vivo FNA biopsies sampled from multiple regions of 38 primary clear cell RCC tumors, ERK phosphorylation differed among patients. In contrast, within individual patients, we found limited intratumoral heterogeneity of ERK phosphorylation. Our results suggest that measuring ERK in a single FNA may be representative of ERK activity in different regions of the same tumor. As diagnostic and therapeutic protein biomarkers are being sought, NIA measurements of protein signaling may increase the clinical utility of renal mass biopsy and allow for the application of precision oncology for patients with localized and advanced RCC. PATIENT SUMMARY: In this report, we applied a new approach to measure the activity of extracellular signal-regulated kinase (ERK), a key cancer signaling protein, in different areas within kidney cancers. We found that ERK activity varied between patients, but that different regions within individual kidney tumors showed similar ERK activity. This suggests that a single biopsy of renal cell carcinoma may be sufficient to measure protein signaling activity to aid in precision oncology approaches., (Copyright © 2018 European Association of Urology. All rights reserved.)

Fentanyl and its analogs have been at the center of the opioid epidemic currently wreaking havoc in the United States. One major element in the opioid crisis is the growing number of clandestine fentanyl labs being reported by enforcement agencies. The development of new analytical methods for detecting and identifying fentanyl and its congeners is among the useful tools in our goal to limit the use of this dangerous family of narcotics. Herein we describe an analytical technique using surface-enhanced Raman spectroscopy (SERS) and a microfluidic device, for detecting fentanyl and two of its chemical precursors, despropionylfentanyl (4ANPP) and N-phenethyl-4-piperidinone (NPP). The vibrational spectra of this family of analytes are very similar, making them difficult to distinguish by traditional means. In addition to taking advantage of the sensitivity provided by SERS, we developed a chemometric approach utilizing a hierarchical partial least squares-discriminant analysis algorithm that allowed us to distinguish spectra that possess many similar features.