Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Histiocytoses are diverse hematopoietic diseases with disabling neurologic involvement. Recently, targeted mitogen-activated protein kinase pathway inhibitors have been used with clinical and radiologic response; however, some patients are unable to tolerate these treatments or have isolated and/or refractory neurologic, ocular, or head and neck (NOHN) disease. Intra-arterial administration of chemotherapy has conferred favorable responses in various neoplasms; however, treatment and outcomes across histiocytosis subtypes have not been examined. METHODS:Patients with biopsy-proven histiocytosis involving NOHN structures underwent an outpatient interventional procedure with angiography, selective catheterization, and intra-arterial infusion of melphalan, with target arteries depending on the site of disease. Patients were followed with radiologic (i.e., PET/CT, CT, MRI, or ophthalmic ultrasound and optical coherence tomography) and quantified functional assessments (i.e., vision, speech, or balance) as appropriate. Complete or partial radiologic and functional response rates were captured as well as frequency of subsequent progression. RESULTS:Eighteen patients underwent 74 total treatment instances. For 14 patients with radiologically evaluable tumorous disease, 10 (71%) had partial or complete response and the remaining 4 had stable disease; 3 of 14 (21%) had subsequent radiologic progression. Of 13 functionally evaluable patients, including 6 with neurodegenerative histiocytosis, 12 (92%) experienced functional improvement; 7 of 13 (54%) had subsequent functional worsening consistent with disease progression. There were no intraprocedural complications; 3 patients required hospitalization following treatment, including 1 patient with allergic reaction to melphalan. DISCUSSION/CONCLUSIONS:For patients with tumorous and neurodegenerative histiocytosis, intra-arterial melphalan represents a safe and highly effective treatment with potential to improve neurologic function. Additional study may clarify patients most suitable for this intervention. This novel treatment modality may represent a practice-changing innovation for refractory histiocytosis involving neurologic and ocular structures, as well as neurodegenerative forms. The treatment delivery form is novel, and future work should be directed at studying the efficacy of this modality to other forms of neurologic, ocular, head, and neck cancers. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class IV evidence that in patients with tumorous or neurodegenerative histiocytosis, selective angiographic catheterization and intra-arterial infusion of melphalan result in radiologic and functional improvement.

This study aimed to assess factors impacting obstetric triage time to disposition. The primary and secondary hypotheses were that high-risk patients and patients evaluated during periods with less staffing would experience prolonged length of stay (LOS), respectively.This single-site, retrospective cohort study analyzed 9,704 obstetric triage visits of 6,182 patients between January 1, 2022, to February 28, 2023. Inclusion criteria included patients 18 years or older with one or more evaluations. Exclusion criteria included scheduled admissions, unknown chief complaints, triage time under 10 minutes, and patients under 18 years old. A total of 6,612 visits representing 4,390 patients were included. The visits were stratified by disposition: admission versus nonadmission (transfer or discharge). Descriptive statistics analyze continuous variables. Frequencies and percentages were calculated for categorical variables. SAS was used for chi-square or Fisher's exact test for categorical variables and the two-sample t-test or Mann-Whitney test for continuous data. Statistical significance was p-value < 0.05.Of 6,612 visits, 3,475 admissions, and 3,137 nonadmissions occurred. The most common chief complaints were contractions (42%), amniotic fluid index evaluation (18%), and preeclampsia evaluation (8%). Admitted compared with nonadmitted patients had shorter LOS (64 minutes vs. 185 minutes, p < 0.001). Admitted compared with nonadmitted patients had shorter LOS by chief complaint, gestational age, high-risk maternal-fetal medicine status, time of day, and day of the week (all p < 0.001).Nonadmitted, maternal-fetal medicine and preterm patients evaluated during daytime and weekdays had significantly longer LOS. Vulnerable populations and target times for triage workflow improvement were identified. · Patient and unit factors influenced LOS.. · Nonadmitted patients had triple the LOS.. · High-risk patients had longer LOS.. · Daytime and weekday visits had longer LOS..

OBJECTIVE:Preterm birth (PTB) remains one of the biggest public health challenges with both obstetric and perinatal implications. While a prior PTB is a known risk factor for recurrence, the understanding of the influence of factors such as race/ethnicity, gestational age, PTB subtypes, and interpregnancy intervals (IPI) remains limited. This study aimed to assess whether these factors modify PTB recurrence risk. METHODS:We conducted a retrospective cohort study of singleton pregnancies in Kaiser Permanente Southern California (2009-2022) using electronic health record data from 82,610 women with two pregnancies and 14,925 women with three. PTB subtypes, spontaneous (sPTB) and indicated (iPTB), were identified through natural language processing. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS:A first PTB was associated with a 6-fold increased risk of PTB in the second pregnancy compared to an uncomplicated pregnancy (23.29% vs. 4.98%, respectively; aOR, 5.60, 95% CI: 5.23-5.99). Those with a history of sPTB (aOR: 5.32, 95% CI: 4.87, 5.81) and iPTB (aOR: 8.26, 95% CI: 7.18, 9.50) had increased risk for the same respective subtype at their second pregnancy. PTB recurrence risk persisted across race/ethnicity categories. In women with PTB in both prior pregnancies, the risk for PTB in a third pregnancy was significantly higher (aOR 14.59, 95% CI 11.28-18.88). The recurrence of PTB between 1st and 2nd pregnancy was substantially higher for those who delivered at 20-33 weeks of gestation, regardless of PTB subtype. Non-Hispanic Black and Asian/Pacific Islander women had higher recurrence risk compared to non-Hispanic Whites. CONCLUSION/CONCLUSIONS:These findings highlight disparities in PTB recurrence by race/ethnicity and PTB subtype among a large integrated healthcare system in Southern California, underscoring the need for targeted interventions, particularly for sPTB.

Marijuana use is common and increasing due to decriminalization, legalization, and expansion of medical use. As a result, the proportion of vascular patients with marijuana is also expected to increase, raising questions if cannabis use affects the incidence and outcomes of vascular disease. Active ingredients of cannabis have been shown to interact with receptors found on vascular endothelium, promoting oxidative stress and endothelial dysfunction. However, current clinical studies have yet to demonstrate a relationship between marijuana use and atherosclerosis. Nonetheless, cannabis arteritis is a rare condition where cannabis is hypothesized to induce vascular inflammation. Future research with high-quality studies is needed to clarify the impact of marijuana use on vascular diseases.

Breast cancer screening recommendations have been established historically for women, but, have been less clearly outlined for men. For average-risk men and younger men less than 25 year of age, imaging is not usually appropriate as a screening test for breast cancer. For men of higher-than-average risk, screening with mammography as annual surveillance imaging is usually appropriate. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

BACKGROUND/UNASSIGNED:Fingolimod is an immunomodulatory drug that has shown promising effects in stroke treatment, including improvements in neurofunctional recovery and a reduction in infarct size. Fingolimod modulates the sphingosine-1-phosphate receptors, which leads to the internalization of sphingosine-1-phosphate receptors on T and B lymphocytes, thereby preventing their egress from secondary lymphoid organs. Here, we report a secondary analysis from the Stroke Preclinical Assessment Network trial. We assessed the effects of fingolimod versus vehicle on stroke outcomes to better evaluate its therapeutic potential. METHODS/UNASSIGNED:The animal population (n=409) comprised male and female animals treated with fingolimod or vehicle. We used 4 clinically relevant models: young healthy mice (10-12 weeks-old), aging mice (16±1 month-old), obesity induced-hyperglycemic mice fed with a high-fat diet for 12 weeks (16 weeks-old), and spontaneously hypertensive rats (16±1 weeks-old). Stroke was induced by the middle cerebral artery occlusion for 1 hour, followed by reperfusion. Animals received a total of 6 intraperitoneal injections of 0.5 mg/kg twice daily of fingolimod or vehicle. Functional outcomes in the corner test and foot-faults test were measured at days 7 and 28. Lesion size and brain morphometry were evaluated at days 2 and 30 by magnetic resonance imaging. RESULTS/UNASSIGNED:Overall, fingolimod did not improve morphological and functional outcomes. However, fingolimod effects varied depending on sex or the comorbidity model. Fingolimod promoted a better outcome in the corner test in aging females. In contrast, it favored a worse outcome in obesity-induced hyperglycemic mice at day 7. Despite having no effect on survival rates or lesion size, fingolimod attenuated the midline retraction at day 30 in aging males, consistent with less atrophy. CONCLUSIONS/UNASSIGNED:Although fingolimod did not significantly benefit the overall primary functional outcome, its effects varied with sex and comorbidity models, underscoring how the therapeutic potential of a particular drug can differ in a heterogeneous population.