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PurposeDCIS has been shown to have a higher rate of positive margins following breast-conserving surgery (BCS) than invasive breast cancer. We aim to analyze certain factors of DCIS, specifically histologic grade and estrogen receptor (ER) status, in patients with positive surgical margins following BCS to determine if there is an association.MethodsA retrospective review of our institutional patient registry was performed to identify women with DCIS and microinvasive DCIS who underwent BCS by a single surgeon from 1999 to 2021. Demographics and clinicopathologic characteristics between patients with and without positive surgical margins were compared using chi-square or Student’s t-test. We assessed factors associated with positive margins using univariate and multivariable logistic regression.ResultsOf the 615 patients evaluated, there was no significant difference in demographics between the patients with and without positive surgical margins. Increasing tumor size was an independent risk factor for margin positivity (P =  < 0.001). On univariate analysis both high histologic grade (P = 0.009) and negative ER status (P =  < 0.001) were significantly associated with positive surgical margins. However, when adjusted in multivariable analysis, only negative ER status remained significantly associated with margin positivity (OR = 0.39 [95% CI 0.20–0.77]; P = 0.006).ConclusionThe study confirms increased tumor size as a risk factor for positive surgical margins. We also demonstrated that ER negative DCIS was independently associated with a higher rate of positive margins after BCS. Given this information, we can modify our surgical approach to reduce rate of positive margins in patients with large-sized ER negative DCIS.

OBJECTIVES/GOALS: Prostate cancer is the 2nd most common cancer among men. 1/3 of these men have a slow-growing disease that can be managed without intervention. Instead of treatment, they can enter an active surveillance program. The goal of this study is to examine if cumulative cancer location can predict one’s disease progression and be used as a clinical marker. METHODS/STUDY POPULATION: This is a retrospective cohort study consisting of men with Gleason Grade 1 prostate cancer enrolled in the Active Surveillance Program at Johns Hopkins. The cohort includes men who were enrolled in the program from 2007 to 2015 before prostate biopsies incorporated multiparametric MRI as of the prostate. We will assess if cumulative cancer location (CCLO), a sum of the total number of histological cancer-positive locations on diagnostic and confirmatory biopsy, can predict grade progression, adverse findings on radical prostatectomy findings, or protocol-based discontinuation. Kaplan Meier survival analyses and multivariable Cox regression will be used to determine if stratifying by CCLO can predict these outcomes. RESULTS/ANTICIPATED RESULTS: We included 1298 men in this study. The study will analyze variables that will be used in multivariable regression. Some variables of interest include age at diagnosis, PSA, PSA density, race/ethnicity, and number of positive cores. We expect that greater variability of tumor location, a higher CCLO score, will lead to more grade progression, protocol-based discontinuation, shorter time on active surveillance and adverse findings after radical prostatectomy. This hypothesis is based on a 2018 study that determined cancer location as a significant predictor of progression at the time of biopsy. Results will be discussed in full at the conference. DISCUSSION/SIGNIFICANCE: Finding a predictive marker of progression at the time of biopsy is clinically significant and can lead to adjusted patient observation and testing while on active surveillance. This will better stratify men on active surveillance, determine who would benefit from genetic testing, and better counsel patients as to how long they will be on surveillance.

There are unresolved questions regarding indications and outcomes of endovascular below-the-knee (BTK) interventions in patients with symptomatic peripheral artery disease (PAD) in real-world clinical practice. We analyzed 884 patients from the multicenter XLPAD registry between 2006 and 2023 with nonstent BTK PAD interventions. Primary outcome: freedom from major adverse limb events (MALE) at 1 year, a composite of all-cause death, major amputation, or clinically driven revascularization. Majority (62.8%) of the BTK interventions were performed for chronic limb threatening ischemia (CLTI), while remaining (37.2%) in patients with intermittent claudication (IC), performed together with an inflow femoropopliteal artery intervention in 58% or involving complex lesion crossings (11.8%). Nearly, 74% were men, mean age 68.0 ± 10.7 years. Mean Rutherford class was 4.65 in CLTI and 2.71 in IC groups. Moderate to severe calcification was present in 25% of cases. Significantly greater number of lesions were treated in the CLTI group (1.84 ± 1.52 vs 2.08 ± 1.61; p = 0.029). Lesion lengths (CLTI: 129.3 ± 85.1 mm vs IC: 115.5 ± 82.5; p = 0.075) were comparable. Nearly, 92% of lesions were treated with balloon angioplasty. Drug-coated balloon use was higher in IC (5% vs 15%, p <0.001), whereas atherectomy use was high in both groups (CLTI: 45.4% vs IC: 49.9%; p = 0.201). Procedural success was similar (CLTI: 92% vs IC: 88.8%; p = 0.098), however 1-year MALE was significantly higher in CLTI patients (30.5% vs 15.8% vs; p <0.0.001), driven by higher all-cause mortality (5.6% vs 2.1% vs; p = 0.014) and major amputations (14% vs 3.7%; p <0.001). Endovascular treatment for BTK PAD is more often performed in patients with CLTI compared with IC, where it is often combined with an inflow artery intervention or complex lesion crossings. Despite similar procedural success, 1-year MALE is significantly higher in CLTI, driven mainly by over a 2-fold increase in all-cause mortality and major amputations.

For endovascular treatment of below-the-knee (BTK) peripheral artery disease (PAD), independently adjudicated real-world outcomes comparing non–stent-based balloon angioplasty (percutaneous transluminal angioplasty) and adjunctive treatments with or without a concomitant ipsilateral femoropopliteal (FP) artery intervention are scarce. A total of 1,060 patients from the multicenter XLPAD registry who underwent non–stent-based BTK PAD intervention between 2006 and 2021 were included. The primary outcome was the 1-year incidence of major adverse limb events (MALEs), a composite of all-cause death, any amputation, or clinically driven repeat revascularization. A total of 566 patients underwent BTK and 494 BTK + FP interventions; 72% were men, with a mean age of 68.4 ± 10.9 years. Diabetes mellitus was more prevalent in the BTK-only group (76.5% vs 69%, p = 0.006). Mean Rutherford class was 4.2 ± 1.18; chronic limb-threatening ischemia was more frequent in the BTK group (55.3% vs 49%, p = 0.040). Moderate to severe calcification was more frequent in the BTK + FP group (21.2% vs 27.1%, p = 0.024), as was lesion length (110.6 ± 77.3 vs 135.4 ± 86.3 mm, p <0.001). Nearly 81% of lesions were treated with percutaneous transluminal angioplasty. Drug-coated balloon (1.6% vs 14%, p <0.001) and atherectomy (38% vs 58.5%, p <0.001) use was more frequent in the BTK + FP group. The rate of procedural success was higher in the BTK + FP group (86% vs 91%, p = 0.009), with amputation being the most common complication at 3.3% within 30 days after the procedure. The rates of 1-year MALE (21.2% vs 22.3%, p = 0.675) and mortality (4.6% vs 3.4%, p = 0.3) were similar between the BTK and BTK + FP groups. Nonstent treatment for BTK PAD with concomitant FP intervention leads to high procedural success and similar rates of 1-year MALE compared with isolated BTK intervention. Condensed Abstract: The vast majority of below-the-knee (BTK) peripheral artery disease (PAD) interventions are performed with balloon angioplasty. Presence of inflow femoropopliteal PAD in patients who undergo BTK interventions can affect the outcome of the procedure. This report explores immediate procedural success and major adverse limb events at 1 year after balloon angioplasty treatment for isolated BTK PAD and in patients who underwent an additional femoropopliteal PAD intervention.

In this article, we present a Bayesian hierarchical model for predicting a latent health state from longitudinal clinical measurements. Model development is motivated by the need to integrate multiple sources of data to improve clinical decisions about whether to remove or irradiate a patient's prostate cancer. Existing modeling approaches are extended to accommodate measurement error in cancer state determinations based on biopsied tissue, clinical measurements possibly not missing at random, and informative partial observation of the true state. The proposed model enables estimation of whether an individual's underlying prostate cancer is aggressive, requiring surgery and/or radiation, or indolent, permitting continued surveillance. These individualized predictions can then be communicated to clinicians and patients to inform decision-making. We demonstrate the model with data from a cohort of low-risk prostate cancer patients at Johns Hopkins University and assess predictive accuracy among a subset for whom true cancer state is observed. Simulation studies confirm model performance and explore the impact of adjusting for informative missingness on true state predictions. R code is provided in an online supplement and at http://github.com/ rycoley/prediction-prostate-surveillance.

There are limited comparative data on real-world outcomes of patients undergoing percutaneous coronary intervention (PCI) of the left main (LM) and non-LM coronary arteries. Total 873 consecutive patients undergoing LM PCI (n = 256) and non-LM PCI (n = 617) were enrolled between September 2019-March 2023 in the Excellence in Coronary Artery Disease (XLCAD) Registry. Primary outcome was 1-year incidence of major adverse cardiovascular events (MACE), a composite of all-cause death, nonfatal myocardial infarction, clinically driven repeat revascularization and ischemic stroke. The secondary outcome was periprocedural (≤30 days) events. Study cohort included 68% men, mean age 71.9 ± 10.3 in LM and 67.2 ± 11.1 years in non-LM PCI groups (p <0.001). LM PCI patients had significantly greater co-morbidities (diabetes mellitus, hyperlipidemia, prior stroke, prior myocardial infarction, prior coronary revascularization, peripheral artery disease, chronic lung and kidney disease and heart failure) compared with non-LM. Acute coronary syndrome indication was the most prevalent (69%). Mechanical circulatory support was employed in 3.1% LM vs 1% non-LM PCI patients (p = 0.026). Mean number of lesions treated were 2.2 ± 1.0 in LM and 1.4 ± 0.6 in non-LM PCI groups (p <0.001). Multivessel PCI was performed in 68.8% LM and 21% non-LM PCI patients (p <0.001). Overall, drug-eluting stent use (96.7%), bifurcation PCI (24.7%) and atherectomy (2.4%) were similar across groups. Technical and procedural success rates were high across groups, however significantly higher in non-LM group. Periprocedural (≤30 days postprocedure) events included mortality in 3.5% LM and 1.5% non-LM PCI (p = 0.334) and MACE 4.7% LM vs 2.4% non-LM PCI (p = 0.080) groups. One-year MACE was significantly higher in LM versus non-LM PCI (12.9% vs 8.4%, respectively; p = 0.043), driven mainly by higher repeat percutaneous revascularization in LM group (12.1% vs 6.2%; p = 0.003). Mortality at 1-year in LM vs non-LM PCI were 10.2% vs 5.8% (p = 0.074). In a real-world experience, LM PCI is performed in patients with significantly greater comorbidities compared with non-LM PCI, with high procedural success. Thirty-day mortality and 1-year MACE are significantly higher in LM group.

Background: To assess the utility of urinary prostate cancer antigen 3 (PCA3) as both a one-time and longitudinal measure in men on active surveillance (AS). Methods: The Johns Hopkins AS program monitors men with favorable-risk prostate cancer with serial PSA, digital rectal examination (DRE), prostate magnetic resonance imaging and prostate biopsy. Since 2007, post-DRE urinary specimens have also been routinely obtained. Men with multiple PCA3 measures obtained over ⩾3 years of monitoring were included. Utility of first PCA3 score (fPCA3), subsequent PCA3 (sPCA3) and change in PCA3 were assessed for prediction of Gleason grade reclassification (GR, Gleason score >6) during follow-up. Results: In total, 260 men met study criteria. Median time from enrollment to fPCA3 was 2 years (interquartile range (IQR) 1–3) and from fPCA3 to sPCA3 was 5 years (IQR 4–6). During median follow-up of 6 years (IQR 5–8), 28 men (11%) underwent GR. Men with GR had higher median fPCA3 (48.0 vs 24.5, P =0.007) and sPCA3 (63.5 vs 36.0, P =0.002) than those without GR, while longitudinal change in PCA3 did not differ by GR status (log-normalized rate 0.07 vs 0.06, P =0.53). In a multivariable model including age, risk classification and PSA density, fPCA3 remained significantly associated with GR (log(fPCA3) odds ratio=1.77, P =0.04). Conclusions: PCA3 scores obtained during AS were higher in men who underwent GR, but the rate of change in PCA3 over time did not differ by GR status. PCA3 was a significant predictor of GR in a multivariable model including conventional risk factors, suggesting that PCA3 provides incremental prognostic information in the AS setting.

Background We estimated SARS‐CoV‐2 Delta‐ and Omicron‐specific effectiveness of two and three mRNA COVID‐19 vaccine doses in adults against symptomatic illness in US outpatient settings. Methods Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS‐CoV‐2 testing within 10 days of illness onset. Using the test‐negative design, we compared the odds of receiving two or three mRNA COVID‐19 vaccine doses among SARS‐CoV‐2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS‐CoV‐2 infection. Vaccine effectiveness (VE) was calculated as (1 − adjusted odds ratio) × 100%. Results Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS‐CoV‐2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA two‐dose recipients and 96% (95% CI: 93% to 98%) for three‐dose recipients. When Omicron predominated, VE was 21% (95% CI: −6% to 41%) among two‐dose recipients and 62% (95% CI: 48% to 72%) among three‐dose recipients. Conclusions In this adult population, three mRNA COVID‐19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID‐19 in the United States. These findings support the recommendation for a third mRNA COVID‐19 vaccine dose.

BackgroundUp to half of men with Gleason score 6 (GS6) prostate cancers initially managed with active surveillance (AS) will eventually require definitive therapy, usually due to tumor grade reclassification during follow-up. We examined the association between PTEN status on biopsy and subsequent clinicopathologic outcomes in men with GS6 cancers who enrolled in AS.MethodsWe performed a case–control study of men enrolled in the Johns Hopkins AS cohort with diagnostic biopsy tissue available for immunohistochemical (IHC) staining. IHC was performed for PTEN using genetically validated protocols for all patients. Cases included men who underwent grade reclassification to GS ≥ 3 + 4 = 7 on biopsy within 2 years of follow-up (i.e., early reclassification) or reclassification to GS ≥ 4 + 3 = 7 on biopsy or radical prostatectomy during follow-up (i.e., extreme reclassification). Control patients were diagnosed with GS6 cancer and monitored on AS for at least 8 years without undergoing biopsy reclassification.ResultsAmong 67 cases with adequate tissue, 31 men underwent early reclassification and 36 men underwent extreme reclassification. Cases were compared to 65 control patients with adequate tissue for assessment. On initial prostate biopsy, cases were older (median age 67 vs. 65, p = 0.024) and were less likely to meet very-low-risk criteria (64 vs 79%, p = 0.042) as compared to controls. Although not statistically significant, PTEN loss was observed in only 1 (1.5%) of 65 controls as compared to 6 (9%) of 67 cases (p = 0.062).ConclusionsPTEN loss was rare among men with GS6 prostate cancer enrolled in AS at Johns Hopkins. Despite this, PTEN loss was more frequent among men who underwent early or extreme reclassification to higher-grade cancer as compared to controls. Additional studies in larger low-risk cohorts may better elucidate a potential role for PTEN in selecting patients for AS.

Background Although psychiatric disorders have been associated with reduced immune responses to other vaccines, it remains unknown whether they influence COVID‐19 vaccine effectiveness (VE). This study evaluated risk of COVID‐19 hospitalization and estimated mRNA VE stratified by psychiatric disorder status. Methods In a retrospective cohort analysis of the VISION Network in four US states, the rate of laboratory‐confirmed COVID‐19‐associated hospitalization between December 2021 and August 2022 was compared across psychiatric diagnoses and by monovalent mRNA COVID‐19 vaccination status using Cox proportional hazards regression. Results Among 2,436,999 adults, 22.1% had ≥1 psychiatric disorder. The incidence of COVID‐19‐associated hospitalization was higher among patients with any versus no psychiatric disorder (394 vs. 156 per 100,000 person‐years, p < 0.001). Any psychiatric disorder (adjusted hazard ratio [aHR], 1.27; 95% CI, 1.18–1.37) and mood (aHR, 1.25; 95% CI, 1.15–1.36), anxiety (aHR, 1.33, 95% CI, 1.22–1.45), and psychotic (aHR, 1.41; 95% CI, 1.14–1.74) disorders were each significant independent predictors of hospitalization. Among patients with any psychiatric disorder, aHRs for the association between vaccination and hospitalization were 0.35 (95% CI, 0.25–0.49) after a recent second dose, 0.08 (95% CI, 0.06–0.11) after a recent third dose, and 0.33 (95% CI, 0.17–0.66) after a recent fourth dose, compared to unvaccinated patients. Corresponding VE estimates were 65%, 92%, and 67%, respectively, and were similar among patients with no psychiatric disorder (68%, 92%, and 79%). Conclusion Psychiatric disorders were associated with increased risk of COVID‐19‐associated hospitalization. However, mRNA vaccination provided similar protection regardless of psychiatric disorder status, highlighting its benefit for individuals with psychiatric disorders.