Publications by Year: 2025

2025

Lee, L. K., Ahmad, F. A., Browne, L. R., Harding, M., Cook, L., Adelgais, K., Burger, R. K., Rogers, A., Tzimenatos, L., Riney, L. C., Rubalcava, D., Ward, C. E., Yen, K., & Leonard, J. C. (2025). Comparison of Cervical Spine Injury Clinical Prediction Rules for Children After Blunt Trauma.. JAMA Network Open, 8(12), e2549403. https://doi.org/10.1001/jamanetworkopen.2025.49403 (Original work published 2025)

IMPORTANCE: Pediatric cervical spine injury (CSI) is a rare occurrence; however, CSI can result in significant disability and death. It is essential to determine the optimal CSI clinical prediction rule to risk stratify children with potential CSI after blunt trauma who require cervical spine imaging.

OBJECTIVE: To compare the test characteristics and projected imaging rates between 3 prospectively derived CSI clinical prediction rules: the Pediatric Emergency Care Applied Research Network CSI prediction rule (PECARN CSI rule), the National Emergency X-Radiography Utilization Study (NEXUS), and the Canadian Cervical Spine (c-spine) rule (CCR).

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study was a planned secondary analysis of a prospective observational study enrolling from December 2018 to October 2021 in 18 PECARN emergency departments. Eligible participants were children up through age 17 years presenting after blunt trauma. Data were analyzed between March 2024 and January 2025.

EXPOSURES: Enrollment in the primary study to develop and validate the PECARN CSI prediction rule.

MAIN OUTCOME MEASURES: Test characteristics with 95% CIs (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV]) and area under the curve (AUC) for the receiver operator curves (ROC) for the detection of CSI using each of the 3 rules. We also estimated the projected c-spine imaging rate (radiography or computed tomography [CT]) based on criteria for each of the 3 rules.

RESULTS: There were 22 430 eligible children enrolled (median [IQR] age 8 [2.0-13.0] years; 13 068 male [58.3%]) and 433 (1.9%) had CSI. C-spine imaging was performed 12 768 children (56.9%): 8912 (39.7%) had radiography and 3856 (17.2%) were imaged with CT. The sensitivity of the 3 rules was: PECARN CSI rule, 93.3% (95% CI, 90.9%-95.7%); NEXUS, 85.7% (95% CI, 82.4%-89.0%); and CCR, 90.8% (95% CI, 88.0%-93.5%). The NPV of the 3 rules was: PECARN, 99.8% (95% CI, 99.7%-99.9%); NEXUS, 99.6% (95% CI, 99.5%-99.7%); and CCR, 99.7% (95% CI, 99.6%-99.8%). Strictly applying each rule resulted in projected CT imaging of 1549 children (6.9%) for PECARN, 2419 (10.8%) for NEXUS, and 2968 (13.2%) for CCR.

CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of CSI prediction rules in children, the PECARN CSI rule had the highest sensitivity and NPV for identifying children at risk for CSI after blunt trauma, with the lowest projected CT imaging rate.

Bernstein, E. Y., Wilson, L. M., Kruse, G. R., Edelman, J., Herzig, S. J., & Anderson, T. S. (2025). Alcohol-Related Hospitalizations From 2016 to 2022.. JAMA Network Open, 8(12), e2550589. https://doi.org/10.1001/jamanetworkopen.2025.50589 (Original work published 2025)

IMPORTANCE: Unhealthy alcohol use contributes to a high rate of mortality. While alcohol use increased during the COVID-19 pandemic, recent trends in alcohol-related hospitalizations are unknown.

OBJECTIVE: To examine US trends in the rate and outcomes of alcohol-related hospitalizations from 2016 to 2022.

DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional study examined hospitalizations among adults aged 18 years or older who were sampled in the National Inpatient Sample, weighted to reflect nationally representative estimates. Data were examined from April to October 2025.

MAIN OUTCOMES AND MEASURES: The primary outcome was alcohol-related hospitalizations, defined using discharge diagnosis codes. Hospitalizations were categorized as primary alcohol use disorder (AUD), primary alcohol-related medical complication, and secondary alcohol-related diagnosis based on discharge diagnosis codes. Secondary outcomes included in-hospital mortality, length of stay, cost of hospitalizations, and discharge disposition.

RESULTS: This study included a weighted 12 912 240 alcohol-related hospitalizations (age 50 to 64 years, 40.4% [95% CI, 40.3%-40.5%]; male, 71.5% [95% CI, 71.4%-71.6%]; Black, 15.6% [95% CI, 15.3%-15.9%]; Hispanic, 11.2% [95% CI, 10.9%-11.4%]; White, 64.9% [95% CI, 64.5%-65.3%]). From 2016 to 2022, the annual rate of alcohol-related hospitalizations per 100 000 remained stable from 721 in 2016 to 688 in 2022 (annual percentage change [APC], -0.43; 95% CI, -1.28 to 0.49) but increased from 70 to 83 among hospitalizations for alcohol-related medical complications (APC, 3.56; 95% CI, 2.19 to 4.94). Trends across demographic groups differed by reasons for hospitalization. In-hospital mortality increased from 2.4% (95% CI, 2.3% to 2.5%) in 2016 to 3.1% (95% CI, 3.0% to 3.2%) in 2022 (P < .001). Mean length of stay increased from 5.6 (95% CI, 5.6 to 5.7) to 6.2 (95% CI, 6.1 to 6.3) days (P < .001), and the rate of self-directed discharges increased from 5.0% (95% CI, 4.8% to 5.2%) to 6.3% (95% CI, 6.1% to 6.5%) (P < .001). Hospitalization costs increased even after accounting for inflation and amounted to $32.6 billion in 2022.

CONCLUSION AND RELEVANCE: In this serial cross-sectional study of nationally representative administrative data from 2016 and 2022, the rate of alcohol-related hospitalizations was stable while mortality, length of stay, and health care costs all increased. Preventive efforts are needed to improve outcomes and reduce health care spending by reducing population-level alcohol consumption and engaging patients in AUD treatment before progression to alcohol-related hospitalizations.

Goldfarb, C. N., Dutton, C., Bastias-Butler, E., Zera, C., Neill, S., & Larson, E. (2025). Abortion Doula Programs Across the United States: A Review of the Current Landscape.. Cureus, 17(12), e100501. https://doi.org/10.7759/cureus.100501 (Original work published 2025)

Abortion doulas support patients who are receiving abortion care. Understanding the abortion doula landscape is critical for patients, clinicians, doulas, and those interested in expanding programs for doula support. We aimed to describe the state of US-based abortion doula programs through a mapping review of the grey literature, documenting programs' characteristics from their online presence (websites, Facebook, Instagram, X). We identified 17 active abortion doula programs. In addition, we identified 30 programs which appeared either to be inactive or to not provide abortion support, primarily in states with post-Dobbs abortion bans. Most active abortion doula programs are community-based, volunteer-run, and free for patients. Three doula programs have partnerships with local clinics; three clinics have in-house doula programs. Most train their own doulas. Most US-based abortion doula programs independently provide community-based, no-cost, volunteer doula services.

Hussain, R., Pickle, E., Lonjin, T., Then, J., Rivosecchi, R., Cassavaugh, J., Fichman, M., & Kaynar, A. M. (2025). Disruption of normal saline supply chain due to a disaster: an analysis of the impact of normal saline shortage on anesthesia practice in a large hospital system and models toward resiliency.. Frontiers in Medicine, 12, 1671978. https://doi.org/10.3389/fmed.2025.1671978 (Original work published 2025)

OBJECTIVES: In the wake of the COVID-19 pandemic and upheaval in the global supply chain, the healthcare sector has grappled with acute shortages of essential resources. Such shortages, while intensified recently in scale and frequency, are not new, as disasters have posed recurrent challenges. An illustrative example is the impact of Hurricane Maria, which severely disrupted the production of normal saline (0.9% NaCl fluid bags) from Puerto Rico-the location of about half of the production of saline for the entire United States. Hospitals relying on "just in time" delivery models found themselves in a precarious situation, prompting a need for innovative solutions to sustain care delivery. The occurrence underscores the vulnerability of healthcare infrastructure to external disruptions and emphasizes the need for adaptive strategies to ensure the resilience of individuals and the system in the face of unforeseen challenges.

METHODS: Our study investigates the impact of Hurricane Maria on saline supplies at the University of Pittsburgh Medical Center (UPMC) and efforts toward building an adaptable model in anesthesia services among providers as well as on a broader, system-wide scale. The study occurred over an 18-month study period, using mixed methods to analyze intravenous (IV) fluid demand and usage patterns before, during, and after the hurricane, integrating qualitative data from 3 months of "participant observation" and survey data.

KEY FINDINGS AND CONCLUSION: System-level adaptation occurred through operating room scheduling, pharmacy-driven standardization, and alternative fluid adoption, while at the individual level, healthcare providers performed drug substitutions, changed mixing practices, and increased reliance on alternative crystalloids. These adaptive measures undertaken at UPMC offer insights for future crises at both the organizational and individual levels within the healthcare system.

Zhao, H., Kakodkar, P., Wang, E., Zhang, D., Niemann, M., Webster, D., Pearce, T., Shoker, A., Keown, P., Sherwood, K., Wu, F., Lewis, C., & Mostafa, A. (2025). An integrative algorithm combining HLA epitope registry, PIRCHE-T2, and PIRCHE-B outcomes to improve immunological risk stratification in kidney transplantation.. Frontiers in Immunology, 16, 1718506. https://doi.org/10.3389/fimmu.2025.1718506 (Original work published 2025)

AIM: Kidney transplantation remains the most effective treatment for end-stage kidney disease. Still, the development of de novo donor-specific antibodies (dnDSA) increases the risk of rejection and allograft failure. While molecular matching algorithms assess B-cell and T-cell epitope mismatches, no single method fully captures rejection risk across immune pathways. This study combines the HLA Epitope Registry (Epregistry), PIRCHE-T2, and PIRCHE-B scores to enhance risk stratification, allowing for early intervention in high-risk recipients and improving long-term outcomes.

METHODS: A retrospective study of 594 kidney transplant recipients in Saskatchewan (1981-2021), Canada, was conducted, tracking de novo donor-specific antibodies (dnDSA) development until January 2024. Epitope mismatch scores were calculated using Epregistry, PIRCHE-T2, and PIRCHE-B, and receiver operating characteristic (ROC) curve analysis determined the optimal cutoff values for predicting dnDSA formation. Patients were categorized into high-risk (all scores > cutoff), intermediate-risk (one algorithm > cutoff), and low-risk (all scores < cutoff) groups. Kaplan-Meier survival analysis evaluated dnDSA-free survival across risk categories.

RESULTS: Among 594 recipients, 104 individuals (17.5%) developed de novo DSA; of these, 29 patients developed more than one, resulting in a total of 146 dnDSA events. The most frequently targeted locus was HLA-DQ (72/146, 49.3%), followed by HLA-DR (25/146, 17.1%) and HLA-A (24/146, 16.4%). The optimal cutoff values for predicting dnDSA were 22.5 (Epregistry), 30.5 (PIRCHE-T2), and 5.5 (PIRCHE-B) for Class I, and 15.5 (Epregistry), 17.5 (PIRCHE-T2), and 5.5 (PIRCHE-B) for Class II (all p < 0.05). Across all molecular mismatch load metrics, Kaplan-Meier analysis demonstrated significantly lower dnDSA-free and antibody-mediated rejection (ABMR)-free survival among high-risk recipients compared with low-risk recipients (log-rank p < 0.001). In addition, both the PIRCHE-T2 score at HLA Class I loci and the overall PIRCHE-T2 score were significantly associated with T-cell mediated rejection (TCMR) (p < 0.01).

CONCLUSION: Integrating Epregistry, PIRCHE-T2, and PIRCHE-B enhances risk stratification for kidney transplant recipients. Epregistry and PIRCHE-B evaluate HLA antibody epitope mismatches, and PIRCHE-T2 focuses on T-cell mismatches. Applied in conjunction, the methods show improved predictive accuracy, making this multi-algorithm approach more effective in identifying high-risk patients. By enabling earlier interventions and personalized immunosuppressive strategies, this model has the potential to improve long-term transplant success.

Rudman, M. K., Badin, S., Ramaraj, S. M., Rangaswamy, S. S., Rauschendorf, P. K., Prakash, R., Boisson-Walsh, A., & Burke, T. F. (2025). Feasibility and integration of a novel bubble CPAP system into a public referral PICU in Mysuru, India.. Frontiers in Pediatrics, 13, 1685939. https://doi.org/10.3389/fped.2025.1685939 (Original work published 2025)

OBJECTIVE: The objective of this study was to evaluate the feasibility of use and integration of a novel bubble CPAP (bCPAP) system into the PICU of the Mysore Medical College and Research Institute, India.

STUDY DESIGN: We conducted an explanatory sequential prospective mixed-methods study using questionnaire-based surveys, focus group discussions (FGDs), and patient records. Survey and FGD participants included nurses, pediatric postgraduates, and pediatricians who worked in the PICU and used the bCPAP system. The FGDs were transcribed, coded, and systematically analyzed for emergent themes using the COM-B framework.

RESULTS: From July 31, 2023, to July 24, 2024, 81 children were treated with the bCPAP system. The median age was 6.5 months (IQR: 3-11), the median weight was 6.5 kg (IQR: 4.9-7.8), and the median treatment duration was 24 h (IQR: 18-38). Most (n = 72, 89%) patients treated with the bCPAP system were discharged home. Forty-eight healthcare workers completed the survey, and 29 participated in the FGDs. Survey respondents rated the bCPAP system as more effective (67%) or much more effective (17%) than previous treatments for respiratory distress. They found the integration of the bCPAP system into the PICU feasible (63%) or very feasible (35%). FGD participants reported that the bCPAP system was easy to use, portable, and required minimal training. They also noted rapid patient improvement and a reduction in the number of patients requiring mechanical ventilation.

CONCLUSION: The bCPAP system was integrated and adopted into the PICU of this public referral facility in Mysuru, India. Further research is needed in additional settings.

Fu, Y., Cao, Y., Cui, Z., Bai, L., Pan, X. N., & Lv, Y. (2025). Comparative study on complications of screws versus plates for comminuted radial head and neck fractures with two or three fragments.. Frontiers in Surgery, 12, 1731596. https://doi.org/10.3389/fsurg.2025.1731596 (Original work published 2025)

BACKGROUND: This retrospective study aimed to compare the efficacy of internal fixation using headless compression screws (HCS) and radial head locking plate (RLP) for comminuted radial head and neck fractures with no more than 3 displaced fragments.

METHODS: This retrospective study included 84 patients with radial head and neck fractures treated at Peking University Third Hospital between January 2013 and December 2022, with 38 and 46 patients in the HCS and RLP groups, respectively. The main outcome was the comparison of complications between the two groups. Demographic data, pre-operative time (POT), operation time (OT), and hospital stay time (HST) were also recorded. The Mayo Elbow Performance Score (MEPS), range of movement of the elbow and forearm, and reasons for re-operation were compared between the two groups.

RESULTS: All patients were followed up for an average of 66.4 months (range, 20-135 months). One patient in each group underwent radial head replacement due to non-union, while the remaining patients achieved bone union. There was no statistically significant difference in the clinical outcomes between the two groups (p > 0.0023). Additionally, the re-operation rate due to symptomatic hardware was significantly higher in the RLP group (28.3%) than that in the HCS group (2.6%, p = 0.002).

CONCLUSION: For internal fixation of comminuted radial head and neck fractures with no more than three displaced fragments, both HCS and RLP achieved good outcomes. However, the RLP increased the incidence of complications and re-operation associated with internal fixation compared to HCS.

Vanderleest, T. E., Gordon, H. B., O’Hare, M., Seifert, P., & Arboleda-Velasquez, J. F. (2025). Pericytes in Notch3 knockout and diabetic mice form engorged connections with vascular endothelial cells.. ScienceBank, 2025. https://doi.org/10.61340/pn3k1dm (Original work published 2025)

PURPOSE: Pericytes, cells crucially important to maintain a healthy microvasculature, make direct connections with vascular endothelial cells, yet the functional significance of these contacts remains largely unexplored. This study aims to investigate the ultrastructural morphological changes that occur in the interactions between pericytes and endothelial cells in mice lacking the Notch3 receptor and in diabetic retinopathy.

METHODS: Serial section transmission electron microscopy (ssTEM) was used to image mouse retinal ganglion cell layer capillaries in wild type (WT; 19 vessels), Notch3 knockout (KO; 16 vessels), conditional Notch3 KO (23 vessels), and diabetic mice (18 vessels). Over 2,000 images were manually segmented to trace the boundaries of the basement membrane, endothelial cells, mural cells, and peg-and-socket connections. Automated image analysis was used to measure contact lengths between pericytes and endothelial cells and peg-and-socket features.

RESULTS: While the vessels analyzed in each group were of similar diameter and pericyte coverage, Notch3 KO vessels had deeper pegs and increased connectivity between pericytes and endothelial cells. In both Notch3 KO and diabetic conditions, there was also an increase in the size of pericyte pegs.

CONCLUSIONS: As the Notch3 receptor plays an important role in cell signaling between pericytes and endothelial cells, and diabetes is also known to disrupt Notch3 signaling, our hypothesis for the enlarged peg phenotype is that the pericytes and endothelial cells actively increase their contact surface to compensate for loss of Notch3 signaling.