Citations

AbstractIn this article, we will discuss the history, pharmacodynamics, and neurotoxicity of psychostimulants and hallucinogens. The drugs discussed are widely used and have characteristic toxidromes and potential for neurological injuries with which the practicing clinician should be familiar. Psychostimulants are a class of drugs that includes cocaine, methamphetamine/amphetamines, and cathinones, among others, which produce a crescendoing euphoric high. Seizures, ischemic and hemorrhagic strokes, rhabdomyolysis, and a variety of movement disorders are commonly encountered in this class. Hallucinogens encompass a broad class of drugs, in which the user experiences hallucinations, altered sensorium, distorted perception, and cognitive dysfunction. The experience can be unpredictable and dysphoric, creating a profound sense of anxiety and panic in some cases. Recognizing the associated neurotoxicities and understanding the appropriate management is critical in caring for these patient populations. Several of these agents are not detectable by standard clinical laboratory analysis, making identification and diagnosis an even greater challenge.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0–72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3–82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.

AbstractWith the rise of the opioid epidemic, the practicing neurologist must recognize the patterns of a growing number of opioid-associated neurological injuries. This is in addition to the classic toxidrome of miosis, altered mental status, and respiratory depression, which must never be overlooked, as it is reversible and potentially lifesaving. Several other idiosyncratic syndromes due to opioid-related nervous system insults are defined by their characteristic imaging findings and portend variable functional recovery. Opioid toxicity can not only lead to brain injury, but also spinal cord and, rarely, peripheral nerve injury. As several newer synthetic opioids are undetectable by most assays, a low threshold to suspect opioid exposure must be maintained.

e15633 Background: Colorectal cancer (CRC) is the fourth most diagnosed cancer, as well as the second leading cause of cancer death in the United States – with an estimated 152,810 diagnoses and 53,010 fatal cases in 2024. Regular screening and early detection can reduce CRC incidence and improve overall survival; however, recent national survey data (2021) demonstrate that only 59% of the US screen-eligible population (≥ age 45) is up to date. Home-based, non-invasive CRC screening test options, such as the multi-target stool DNA (mt-sDNA) test, have the potential to improve patient outcomes and overcome CRC screening adherence barriers at multiple levels. Given that the recommended interval for mt-sDNA is three years, a better understanding of use in repeat users is warranted. We evaluated the effective rescreen rate of previous mt-sDNA test users. Methods: In this retrospective cohort study, we included patients between the ages of 45 and 75 years who were shipped an mt-sDNA test kit between January 1st – December 31st, 2023, and had previously completed mt-sDNA screening with a negative result > 2.5 years prior. Our primary variable of interest was mt-sDNA completion rate on repeat testing, defined as kit receipt with a valid result within 120 days of the shipment date. Regression analysis was performed to determine baseline characteristics associated with repeat test completion rate. Results: During the analysis period, a total of 481,748 patients who met the inclusion criteria received an mt-sDNA kit. The majority of the cohort was female (61.4%) and between the ages of 65-75 years (50.9%). Overall repeat test completion rate was 83.6%, with the average time to kit return being 18.9 days. Completion rates were similar between males (83.8%) and females (83.6%), and patients receiving included navigation support via mobile phones demonstrated the shortest average time to kit return (18.7 days). Completion rates increased concordantly with patient age: 81.6%, (45-49 years), 82.2% (50-64 years), and 85% (65-75 years). For first-time rescreen participants (2nd lifetime mt-sDNA test), the completion rate was 83.1%. For second-time rescreen participants (3rd lifetime mt-sDNA test), the completion rate was even higher at 93.6%. Logistic regression analyses revealed that patients re-screening for a second-time were three times more likely to return the mt-sDNA kit for CRC screening (OR = 3.118; p < 0.001). Conclusions: Data from this large, retrospective cohort study revealed that repeat CRC screening with the mt-sDNA test is associated with high adherence to triennial follow-up among participants. suggesting a high-level of perceived patient confidence in repeat performance of the mt-sDNA test. These novel data provide relevant insights regarding strong patient willingness to continue with home-based, non-invasive mt-sDNA testing over multiple cycles of average-risk CRC screening.

AbstractBackgroundTechnology has revolutionized not only direct patient care but also diagnostic care processes. This study evaluates the transition from glass‐slide microscopy to digital pathology (DP) at a multisite academic institution, using mixed methods to understand user perceptions of digitization and key productivity metrics of practice change.MethodsParticipants included dermatopathologists, pathology reporting specialists, and clinicians. Electronic surveys and individual or group interviews included questions related to technology comfort, trust in DP, and rationale for DP adoption. Case volumes and turnaround times were abstracted from the electronic health record from Qtr 4 2020 to Qtr 1 2023 (inclusive). Data were analyzed descriptively, while interviews were analyzed using methods of content analysis.ResultsThirty‐four staff completed surveys and 22 participated in an interview. Case volumes and diagnostic turnaround time did not differ across the institution during or after implementation timelines (p = 0.084; p = 0.133, respectively). 82.5% (28/34) of staff agreed that DP improved the sign‐out experience, with accessibility, ergonomics, and annotation features described as key factors. Clinicians reported positive perspectives of DP impact on patient safety and interdisciplinary collaboration.ConclusionsOur study demonstrates that DP has a high acceptance rate, does not adversely impact productivity, and may improve patient safety and care collaboration.

ABSTRACT Chronic wound infections can be difficult to treat and may lead to impaired healing and worsened patient outcomes. Novel treatment strategies are needed. This study evaluated the effects of intermittently produced hydrogen peroxide (H 2 O 2 ) and hypochlorous acid (HOCl), generated via an electrochemical bandage (e-bandage), against methicillin-resistant Staphylococcus aureus biofilms in an agar membrane biofilm model. By changing the working electrode potential, the e-bandage generated either HOCl (1.5 V Ag/AgCl ) or H 2 O 2 (−0.6 V Ag/AgCl ). The degree of biocidal activity of intermittent treatment with HOCl and H 2 O 2 correlated with HOCl treatment time; HOCl treatment durations of 0, 1.5, 3, 4.5, and 6 hours (with the rest of the 6-hour total treatment time devoted to H 2 O 2 generation) resulted in mean biofilm reductions of 1.36 ± 0.2, 2.22 ± 0.16, 3.46 ± 0.38, 4.63 ± 0.74, and 7.66 ± 0.5 log CFU/cm 2 , respectively, vs. non-polarized controls, respectively. However, application of H 2 O 2 immediately after HOCl treatment was detrimental to biofilm removal. For example, 3 hours HOCl treatment followed by 3 hours H 2 O 2 resulted in a 1.90 ± 0.84 log CFU/cm 2 lower mean biofilm reduction than 3 hours HOCl treatment followed by 3 hours non-polarization. HOCl generated over 3 hours exhibited biocidal activity for at least 7.5 hours after e-bandage operation ceased; 3 hours of HOCl generation followed by 7.5 hours of non-polarization resulted in a biofilm cell reduction of 7.92 ± 0.12 log CFU/cm 2 vs. non-polarized controls. Finally, intermittent treatment with HOCl (i.e., interspersed with periods of e-bandage non-polarization) for various intervals showed similar effects (approximately 6 log CFU/cm 2 reduction vs. non-polarized control) to continuous treatment with HOCl for 3 hours, followed by 3 hours of non-polarization. These findings suggest that timing and sequencing of HOCl and H 2 O 2 treatments are crucial for maximizing biofilm control when using an e-bandage strategy.

Abstract Background: In breast cancer, the spatial relationship between immune and tumor cells is increasingly recognized as critical in determining the efficacy of neoadjuvant therapy (NAT). This study investigated how the distribution of immune cells, particularly CD8+ T cells, relative to tumor cells affects treatment outcomes. Methods: Biopsies from 104 breast cancer patients were examined, both pre- and post-NAT, using multiplex immunohistochemistry (mIHC). This study focused on the density and distribution of CD8+ T cells, CD68+ macrophages, FoxP3+ regulatory T cells, and other immune markers. Results: The spatial proximity of CD8+ T cells within 20 µm of cancer cells (N20-CD8+T) was strongly correlated with improved clinical outcomes across diverse tumor subtypes and NAT regimens. A significant post-NAT decrease in CD4+, CD68+, and FoxP3+ cells highlights notable shifts in the tumor immune landscape. A noteworthy finding was the positive correlation between CXCL9 expression and N20-CD8+T cells, suggesting a mechanism for immune cell recruitment and interaction within the tumor microenvironment. These results highlight the complex interplay among NAT, immune cell modifications, and patient outcomes. Conclusions: This study revealed that the proximity of N20-CD8+ T cells to tumor cells is consistently associated with favorable NAT outcomes, transcending tumor subtypes, and treatment differences. This highlights the potential of immune cell dynamics, especially CD8+ T cells, as predictive biomarkers for therapeutic responses in breast cancer, underscoring their vital role in tumor immunity.

Background The mortality risk attributable to moderate aortic stenosis (AS) remains incompletely characterized and has historically been underestimated. We aim to evaluate the association between moderate AS and all‐cause death, comparing it with no/mild AS (in a general referral population and in patients with heart failure with reduced ejection fraction). Methods and Results A systematic review and pooled meta‐analysis of Kaplan–Meier‐derived reconstructed time‐to‐event data of studies published by June 2023 was conducted to evaluate survival outcomes among patients with moderate AS in comparison with individuals with no/mild AS. Ten studies were included, encompassing a total of 409 680 patients (11 527 with moderate AS and 398 153 with no/mild AS). In the overall population, the 15‐year overall survival rate was 23.3% (95% CI, 19.1%–28.3%) in patients with moderate AS and 58.9% (95% CI, 58.1%–59.7%) in patients with no/mild aortic stenosis (hazard ratio [HR], 2.55 [95% CI, 2.46–2.64]; P <0.001). In patients with heart failure with reduced ejection fraction, the 10‐year overall survival rate was 15.5% (95% CI, 10.0%–24.0%) in patients with moderate AS and 37.3% (95% CI, 36.2%–38.5%) in patients with no/mild AS (HR, 1.83 [95% CI, 1.69–2.0]; P <0.001). In both populations (overall and heart failure with reduced ejection fraction), these differences correspond to significant lifetime loss associated with moderate AS during follow‐up (4.4 years, P <0.001; and 1.9 years, P <0.001, respectively). A consistent pattern of elevated mortality rate associated with moderate AS in sensitivity analyses of matched studies was observed. Conclusions Moderate AS was associated with higher risk of death and lifetime loss compared with patients with no/mild AS.

Abstract Objectives: Mammographic microcalcifications (calcs) are a sentinel marker of in-situ and invasive breast cancer (BC) but most calcs reflect benign breast disease (BBD). BBD comprises a diverse set of lesions, variably associated with increased BC risk. While calc frequency data for the modern era are limited, historically, calcs were reported in 11% of BBD biopsies. Some studies suggest that calcs in BBD impact BC risks; however, the frequency and BC risks associated with calcs during the percutaneous biopsy era have not been clearly established. Accordingly, we assessed the association of calcs with specific BBD lesions and BC risk in a large contemporaneous BBD cohort including detailed pathology review. Methods: A cohort of 4,819 patients with percutaneously diagnosed BBD from 2002-2013 at Mayo Clinic, were identified. The cohort was followed from 6 months after biopsy until censoring, BC diagnosis, or December 2021. Mean follow-up was 11.3 (SD=5.1) years for BBD patients who remained cancer-free in follow-up compared with 7.4 (SD=4.3) years for cases. Histology of all biopsies were reviewed microscopically to record pathologic findings. A natural language processing algorithm (NLPA) was developed and utilized to identify the presence of calcs based on pathology reports. NLPA results were compared to 300 matched biopsy reports, taken as ground truth. We performed age-adjusted Cox proportional hazards regression to assess hazard ratios (HRs) with 95% confidence intervals (CIs) for specific BBD lesions, stratified by the presence (calc+) or absence of calcs (calcs-), with estimation of an interaction term to test for differences in risks by calc strata. Standardized incidence ratios (SIRs) estimated risks for calc+ and calc- BBD lesions versus matched strata for Iowa SEER population-based BC incidence rates. Results: The NLPA achieved sensitivity=0.993 and specificity=0.986. Overall, 42.8% of BBD biopsies were calc+, including 49.1% of biopsies preceding BC and 42.4% of biopsies not preceding BC (Chi-square p=0.02). Overall, risks of BC among women with BBD calc+ biopsies did not differ significantly from those of women with calc- BBD: HR=1.13 (95% CI: 0.90,1.41), p=0.290. SIRs were also similar for the two groups; women with BBD calc+ biopsies had an SIR =2.00 (95% CI: 1.72, 2.33) and BBD calc- biopsies yielded an SIR= 1.91 (95% CI: 1.64,2.22) (Table 1). HRs were similar for specific calc+ and calc- BBD lesions, with progressively higher risks for non-proliferative disease (NP), proliferative disease without atypia (PDWA) and atypical hyperplasia (AH) (pinteraction=0.55). Interaction terms were not significant for any specific lesion, apart from a marginally significant result for dilated ducts, wherein risks were marginally higher for calc- lesions (pInteraction =0.048), perhaps representing a chance finding. SIRs for calc+ versus calc- BBD lesions were also similar. Overall, 77.3% of AH was calc+; for AH calc+, SIR=3.76 (95%CI: 2.74-5.17) and for AH calc-, SIR=4.41 (95%CI: 2.56-7.59). Conclusion: In this recent, larger percutaneous BBD cohort, calcs were present in 42.8% of all specimens, representing a marked increase compared with historical BBD data, particularly those dominated by surgical biopsy for diagnosis and preceding implementation of full-field digital mammography. In this study, calcs in percutaneously diagnosed BBD were not associated with increased BC risk. Table 1: Comparison of standard incidence ratio of subsequent breast cancer with and without microcalcifications in benign breast disease by histologic impression (NP = non-proliferative disease, PDWA = proliferative disease without atypia, and AH = atypical hyperplasia). (1) compared to Iowa SEER population Citation Format: Sarah Schrup, Robert Vierkant, Stacey Winham, Celine Vachon, Derek Radisky, Jodi Carter, Laura Pacheco-Spann, Matthew Jensen, Amy Degnim, Mark Sherman. Benign breast disease and microcalcifications in percutaneous biopsies and breast cancer risk [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS07-02.