Publications by Year: 2025

BACKGROUND AND AIMS: Liver stiffness measurement (LSM) by vibration-controlled transient elastography correlates well with liver-related events (LREs), but previous head-to-head comparisons with liver histology were limited by small sample size. This study aimed to compare the prognostic performance of LSM and histology for predicting LREs in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

APPROACH AND RESULTS: We analyzed data from 3532 metabolic dysfunction-associated steatotic liver disease patients (mean age 51.9 y, 57.3% male) in the multicenter vibration-controlled transient elastography-prognosis cohort, all having undergone both LSM and liver biopsy. The primary outcome was LREs, defined as hepatic decompensation, liver transplantation, or liver-related death. Secondary outcomes included HCC and decompensation analyzed separately. Median baseline LSM was 8.8 kPa; 33.5% had F3-F4 fibrosis. Over a median follow-up of 56.6 months, 126 patients (3.6%) developed LREs (123 decompensation). LSM and histology demonstrated similar prognostic performance for LREs, with comparable 5-year AUROC values (0.870 vs. 0.869), integrated AUROCs (0.878 vs. 0.852), and integrated precision-recall curves (0.137 vs. 0.0.68). The 5-year integrated Brier scores were also similar (1.389% vs. 1.391%), and the integrated discrimination improvement index showed no significant difference. Similar results were found across all the outcomes, time points, and sensitivity analyses.

CONCLUSIONS: In this large metabolic dysfunction-associated steatotic liver disease cohort, LSM by vibration-controlled transient elastography showed comparable prognostic accuracy to histology. As a noninvasive tool, LSM may serve as an alternative surrogate endpoint in clinical trials.

DESCRIPTION: Babesiosis is a tick-borne disease that is endemic in the United States (US). The major species, Babesia microti, is readily transmissible via blood transfusion. Since 2019, blood donors in 14 US states and Washington DC have been routinely screened for Babesia infection using highly sensitive and specific nucleic acid testing (NAT). Currently, there are no recommendations regarding the management of asymptomatic blood donors who test positive for Babesia.

METHODS: A multidisciplinary expert panel was convened to develop guidance for the management of asymptomatic Babesia-infected blood donors. A survey was distributed through the Infectious Diseases Society of America (IDSA) Emerging Infections Network (EIN) to evaluate how a geographically diverse group of infectious diseases specialists would approach this problem.

RESULTS: The expert panel recommends that all Babesia NAT positive blood donors should be referred for clinical evaluation and retested using peripheral blood smear (PBS) and B. microti PCR within two months of blood donation screening. The panel also recommends observation rather than treatment for a reactive molecular test alone. Antimicrobial therapy should be considered for PBS positive cases. Donors should be counseled regarding the typically self-limiting nature of this infection and instructed to seek medical care if symptoms develop. The EIN survey results are consistent with these recommendations.

CONCLUSIONS: Several factors support these management recommendations. Blood donors typically comprise healthy, immunocompetent adults in whom most Babesia infections are self-limited based on studies showing that molecular evidence of infection clears in almost all asymptomatic blood donors without intervention.

INTRODUCTION: Increasing the diversity of medical students is a challenge and priority in many countries. In France, systems-level changes have been introduced to attract candidates from diverse backgrounds, specifically the traditional pathway to medical studies, the PASS (Parcours Accès Spécifique Santé/Specific Access to Health Training, biomedical sciences-focused) has been supplemented with a second pathway, the LAS (Licence Accès Santé/Bachelor's Degree with Access to Health Studies) combining a broader major with a health-access module. This study is the first to assess the effectiveness of the LAS in increasing the social, geographic, and sex diversity of candidates admitted to Medical or Dental Schools in France.

METHODS: This prospective cohort included candidates to health studies. Socioeconomic origin was determined according to parents' profession. Primary outcome was admission to Medical or Dental School. Mediation analysis assessed the role of prior academic performance (assessed by the French Baccalaureate grade) between socioeconomic origin and admission.

RESULTS: Among 2,059 candidates (women: 70%), 230/1,534 PASS (15% of admission, women: 55%, upper socioeconomic origin: 68%) and 43/525 LAS (8% of admission, women: 74%, upper socioeconomic origin: 49%) were admitted to Medical or Dental School. In multivariable logistic regression, sex (OR = 0.37 for women, 95%CI [0.26-0.53], p<.001), upper socioeconomic origin (OR = 1.78, 95%CI [1.20-2.64], p<.01), and prior academic performance predicted admission in PASS (OR = 5.57, 95%CI [2.90-10.7], p<.001). In LAS, only prior academic performance was independently associated with admission (OR = 8.93, 95%CI [3.99-20.0], p<.001). Prior academic performance partially mediated the effect of socioeconomic origin on admission in PASS, and fully mediated the effect in LAS.

DISCUSSION: Introducing the LAS pathway measurably improved diversity among admitted students and reduced socioeconomic and sex-related disparities. In contrast, the historical PASS system continues to reinforce these inequities. By widening the academic lens used for selection, LAS shows that reforms can meaningfully counteract social reproduction while maintaining academic rigor.

OBJECTIVES: To analyze obstetric ultrasound utilization and expenditures per live birth delivery among the commercially insured from 2016 to 2022 and present updated trends and variation in use by type of ultrasound and across subgroups.

METHODS: In this retrospective United States-based cohort study, obstetric ultrasound utilization and expenditures during pregnancy were measured for a cohort of all deliveries with at least 28-week gestation that resulted in a live birth between January 1, 2017 and December 31, 2022, using the Health Care Cost Institute commercial claims database. We report utilization trends and the clinical and sociodemographic factors correlated with utilization using descriptive statistics and negative binomial regression.

RESULTS: In our sample of 1,731,823 pregnancies, there were an average of 5.3 (SD ± 3.9) claims for obstetric ultrasounds per live birth delivery. After adjusting for covariates, the number of ultrasounds per live birth increased by 8.3% and inflation-adjusted spending for these ultrasounds increased 5.6% over the 7-year study period (p < .001); though utilization decreased during the COVID-19 pandemic in 2020. Follow-up ultrasound (CPT 76816) was the fastest growing procedure.

CONCLUSION: Obstetric ultrasound utilization and expenditures increased from 2016 to 2022. Information on the variation in patterns and trends related to obstetric ultrasound use may assist policy makers in their assessment of resource utilization and approach to reimbursement design, such as obstetric bundled payments.

BACKGROUND: Participation in American-style football (ASF) results in trauma-related concerns including joint injuries. Limited work has described arthritis and knee and hip total joint arthroplasty (TJA) in this population. The association of these conditions to pain interference and physical and mental function has not been well described.

OBJECTIVES: 1. To characterize demographic, football, and health-related factors in former ASF players associated with arthritis and knee or hip TJA. 2. To investigate the association of arthritis and knee or hip TJA with pain interference and physical and mental function.

STUDY DESIGN: Cross-sectional cohort study.

SETTING: Academic medical multisite hospital system.

PARTICIPANTS: Former ASF players who played professionally from 1960 to 2019.

ASSESSMENT OF RISK FACTORS: Self-completed standardized questionnaires.

MAIN OUTCOME MEASURES: Surveys included self-reported arthritis and knee and hip TJA, Patient-Reported Outcome Measure Instrument Scale (PROMIS), physical function and mental function, and pain interference scales. Multivariable logistic regression models assessed the association between demographic, football-related, and health characteristics with arthritis and knee and hip TJA. Multivariable linear regression models evaluated the association between arthritis and knee and hip TJA with pain interference and physical and mental function.

RESULTS: In 4189 former ASF players (average and SD: 51.8 ± 14.4 years old) over half (n = 2237, 53.4%) had arthritis (n = 1547) or knee or hip TJA (n = 690). Both arthritis and knee and hip TJA were more common in those who were older, with higher body mass index, and prior surgery during playing years and were linemen (p < .05). Additionally, arthritis was more common in players who were never married (p = .01) and with higher concussion symptoms score (p < .001). Knee and hip TJA were more common in players who self-identified as White (p < .001). Both arthritis and knee and hip TJA were associated with greater pain interference and reduced physical function (all p < .001) but not with mental function.

CONCLUSION: More than half of former ASF players reported arthritis or knee or hip TJA. Higher pain interference and reduced physical function in former ASF players with arthritis and knee or hip TJA highlight the importance of advancing strategies to prevent and treat joint conditions.

OBJECTIVE: To assess the baseline haemodynamic parameters in Best Endovascular Therapy versus Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial patients and to analyse the change after revascularisation (ClinicalTrials.gov identifier: NCT02060630).

METHODS: Baseline and 30 day post-operative assessment parameters included ankle brachial index (ABI), toe pressure (TP), and toe brachial index. Statistical analyses were performed according to the actual treatment received and carried out separately in each cohort.

RESULTS: Cohort 1 included patients who had a single segment of great saphenous vein available. At baseline, median ABI was 0.51 (interquartile range [IQR] 0.38, 0.68) and median TP was 33 mmHg (IQR 28.5, 48 mmHg), with no statistically significant differences between the surgical and endovascular groups. The median ABI increase was 0.44 (IQR 0.25, 0.60) in the bypass group and 0.44 (IQR 0.25, 0.61) in the endovascular group (p = .55). The median TP increase in the surgical group was 40 mmHg (IQR 13, 60 mmHg), compared with 29 mmHg (IQR 9, 54 mmHg) in the endovascular group (p = .032). An ABI increase of > 0.30 and or a TP increase of > 30 mmHg was noted in 92.4% and 90.1% of the patients in the surgical and endovascular groups, respectively (p = .33). Cohort 2 included patients who needed an alternative bypass conduit. The median ABI increase in the surgical and endovascular groups was 0.40 and 0.52 (p = .50), respectively. The median TP increase in the surgical group was 36 mmHg (IQR 7, 65 mmHg), compared with 47 mmHg (IQR 22, 65 mmHg) in the endovascular group (p = .27). An ABI increase of > 0.30 and or a TP increase of > 30 mmHg was noted in 91.0% and 90.7% of the patients in the surgical and endovascular groups, respectively (p = .94).

CONCLUSION: In patients for whom a comparison was available, > 90% had statistically significantly improved haemodynamic values 30 days after revascularisation. A greater increase in TP was noted with surgical bypass than with endovascular revascularisation among patients who had a single segment great saphenous vein available.

Persisters are a rare sub-population of tumor cells that survive anti-cancer therapy and are thought to be a major cause of recurrence. These cells have been identified following both drug- and immune-therapy but are generally considered to be distinct entities. Since both pharmacological agents and immune cells often kill via apoptosis, we tested a hypothesis that both types of cells survive based on reduced mitochondrial apoptotic sensitivity, which in turn would yield a similar and reciprocal multi-agent resistant phenotype. Supporting this hypothesis, we indeed observed that IPCs acquired a reduced sensitivity to multiple drug classes and radiotherapy, suggesting non-immune mechanisms are important in the survival of cancer cells after immunotherapy. Likewise, DTPs developed not only a reduced sensitivity to multiple drug classes and radiotherapy, but also acquired a reduced sensitivity to T cell killing. Both IPCs and DTPs developed decreased sensitivity to mitochondrial apoptosis. A sub-population of IPCs downregulated antigen and upregulated PD-L1. Intriguingly, in the IPCs that didn't employ these mechanisms of resistance, a greater decrease in sensitivity to mitochondrial apoptosis was observed, suggesting that the presence or absence of a resistance mechanism can exert selective pressures over the emergence of others. Targeting anti-apoptotic dependencies in persisters increased sensitivity to chemotherapy or CAR T therapy. These results suggest that common biological mechanisms underly survival of persisters, whether derived from immune or drug therapy, and offer an explanation for the acquired cross-resistance to these two types of therapies often observed in the clinic.

Maritime operations conducted by military Special Operations Forces and civilian special weapons and tactics (SWAT) units present unique medical challenges. These missions often occur in unpredictable environments, far from immediate medical resources and with exposure to waterborne threats. This article examines the medical aspects critical to maritime operations, including hypothermia management, trauma care in confined and moving spaces, management of drowning and respiratory issues, and specialized training for maritime-specific injuries. A narrative review of literature from 2005-2024 was conducted across major databases and grey sources, with studies included by author consensus. The review identified core maritime medical challenges, hypothermia, drowning, confined-space trauma, respiratory hazards, motion sickness, and impact injuries. Medical support tailored to these environments is essential for maintaining operational effectiveness and responder safety. By examining both preventive and responsive medical approaches, this article highlights the need for maritimespecific medical protocols and training.

BACKGROUND: Polyethelene glycol (PEG) is a key component of several ultrasound enhancing agents (UEA) but has been recognized as contributing to anaphylactoid reactions, resulting in new contraindications to use in those with known or suspected PEG allergy. Despite these recommendations, no clinical tools currently exist to screen for those with suspected PEG-allergy in echocardiography laboratories.

METHODS: We developed a screening survey to identify patients with potential PEG allergy and prospectively implemented it in a pilot study involving 8 patients with confirmed PEG allergy by skin prick testing and 50 prospectively enrolled patients undergoing clinically-indicated echocardiography without known PEG allergy, June - July 2025.

RESULTS: All patients completed the survey. A positive response to at least 2 of the first 4 questions on the screening survey had a sensitivity of 100% (95% CI 67.6-100%), specificity of 100% (95% CI 92.9-100%), positive predictive value of 100% (95% CI 67.6-100%), and a negative predictive value of 100% (95% CI 92.9-100%) to identify individuals with known PEG allergy.

CONCLUSIONS: In this pilot multicenter study, a brief screening survey identified all patients with proven allergy to PEG, suggesting possible utility to its use to identify those with potential PEG allergy who would benefit from a non-PEGylated UEA, though further clinical validation is needed.