Citations

Abstract Purpose: Squamous cell carcinoma of the anus (SCCA) is primarily driven by human papillomavirus (HPV) infection. Up to 30% of patients experience recurrence, necessitating improved surveillance strategies. Liquid biopsies have shown promise as a tool in oncology. This study investigates the clinical performance of circulating tumor tissue modified viral (TTMV)- HPV DNA in the post-treatment surveillance of SCCA. Patients and methods: This central IRB-approved retrospective cohort study included 117 patients diagnosed with HPV-driven SCCA from seven U.S. centers who had ≥1 TTMV-HPV DNA tests (NavDx®, Naveris, Inc., Waltham, MA) performed between March 2020 and June 2024. TTMV-HPV DNA for HPV subtypes 16, 18, 31, 33, and 35 were analyzed using droplet digital PCR. The diagnostic accuracy of TTMV-HPV DNA was evaluated by comparing test results with clinical evidence of SCCA recurrence determined through anoscopy, radiology, and/or tissue biopsy. Recurrence is defined as either a positive biopsy or subsequent salvage therapy. Results: Patients were primarily female (73%) with a median age 63 years. Median follow-up after initial treatment was 19 months. Forty-seven patients (40%) had pretreatment TTMV-HPV DNA testing, with a baseline detectability of 85.1% (40/47, 95% CI: 74.9–95.3). Of these, 24 were re-tested within 3 months post-treatment and 18 had undetectable TTMV-HPV DNA (75%). Those patients whose scores became undetectable had significantly longer recurrence-free survival than those whose scores remained detectable (log-rank test, p=0.01). One hundred and four patients (89%) underwent post-treatment testing, of which 91 provided relevant data for the analysis. Of these 91 patients, 27 (29.7%) experienced recurrence. Post-treatment testing demonstrated a per- patient sensitivity of 85.7% (24/28, 95% CI: 72.8-98.7). Of four patients with a false negative test, only one had biopsy-confirmed recurrence, whereas the remaining recurrences were not biopsied prior to starting salvage treatment. The positive predictive value of a single positive test was 97.6% (40/41; 95% CI: 92.8–100.0). One patient remains in active follow-up. Of the true positive post-treatment tests, 58% (14/24) predicted recurrence before clinical detection, with a median lead time of 59 days (range: 10–536). There were 141 negative post-treatment tests across 66 patients. This yielded a per-test specificity and negative predictive value of 99.3% (136/137, 95% CI: 97.8-100.0) and 97.2% (136/140, 95% CI: 94.9-99.9), respectively. Indeterminate TTMV-HPV DNA tests were rare (5/268,1.9%). However, clinically indeterminate findings (CIFs) were common, with 141 post-treatment CIFs identified across 52/117 patients (44.4%). TTMV-HPV DNA testing was able to correctly predict recurrence status in 94.3% of CIF cases. Conclusion: TTMV-HPV DNA testing is a sensitive and specific surveillance method for detecting early recurrence of HPV-driven SCCA. Citation Format: Shane Lloyd, Rafi Kabarriti, James Jabalee, Tyler Slater, Corbin Jacobs, Sean Inocencio, Michael Rutenberg, Chance Matthiesen, Kasha Neff, Gene-Fu F Liu, Tiffany M Juarez, Catherine DV Fitz, Stanley Liauw. Plasma-based circulating tumor tissue modified viral (TTMV)-HPV DNA for detection of recurrent HPV-driven anal cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B018.

Background: In recent years, catheter ablation has emerged as a sustainable, first-line therapy for the management of ventricular tachycardia (VT). Given the rise of the “obesity paradox” theory in atrial ablation outcomes, we sought to study the effect of BMI on patients undergoing structural VT ablation. Purpose: To assess the outcomes of VT ablation, specifically VT recurrence, in patients with elevated vs. normal BMI. Methods: Clinical characteristics and demographic data were collected for VT patients who underwent ablation at Mayo Clinic Rochester from 2012-2022. Patient BMI was classified as non-obese (<30 kg/m2), obese (30-40 kg/m2), and morbidly obese (≥40 kg/m2). The endpoint was a composite of initial monomorphic VT recurrence and repeat ablation after adjusting for age, sex, and comorbidities. Results: A total of 399 patients underwent 508 ablations. 51.4% of ablations had a BMI <30, 39.2% were between 30-40, and 9.4% were ≥40. There was a greater prevalence of hypertension and type 2 diabetes mellitus in morbidly obese patients (p <0.01). Morbidly obese individuals also had a significantly increased rate of general anesthesia during ablation and long VT cycle lengths. The Kaplan-Meier curve demonstrates no statistically significant differences in time to VT recurrence among the three BMI groups (p = 0.324). Neither morbid-obesity (aHR= 1.20; CI = 0.94-1.56, p = 0.14) nor nonmorbid-obesity (aHR = 0.92; CI = 0.76-1.10, p = 0.4), compared to non-obesity was a significant independent predictor of VT recurrence or repeat ablation on multivariate regression after adjusting for age, sex and comorbidities. Conclusion: There was no significant association between BMI groups and VT recurrence or repeat ablation, and no difference in complications. We did not find the obesity paradox to be relevant for VT ablation in our patient population. Further study would be needed with larger samples to corroborate these findings.

Abstract Racial inequities in postpartum weight have been documented with limited studies on the influences of racism and other forms of discrimination. In a prospective longitudinal study applying ecological momentary assessment (EMA) and ambulatory assessment of weight, we measured the association between discrimination, stress, and postpartum weight change. The Postpartum Mothers Mobile Study is a cohort of 313 pregnant and birthing individuals who were followed during their second and third trimesters through 1 year postpartum. They were recruited in clinical settings between 2017 and 2020 in a major city center in Pennsylvania. Measures of racism and gender-based discrimination were collected via random EMA surveys throughout pregnancy and postpartum, and weight was collected via Bluetooth-enabled scales at least weekly. Among Black participants, a 10% increase in the number of days a participant experienced racial discrimination in the past month was associated with retaining 0.3 more pounds, a 10% increase in EMA gender discrimination was associated with retaining 0.4 more pounds, and EMA stress reported in the past month was associated with decreased weight retention. Chronic experiences of racial and gender discrimination may contribute to weight retention immediately after pregnancy and beyond.

Abstract 3D printing, also known as additive manufacturing, holds immense potential for rapid prototyping and customized production of functional health‐related devices. With advancements in polymer chemistry and biomedical engineering, polymeric biomaterials have become integral to 3D‐printed biomedical applications. However, there still exists a bottleneck in the compatibility of polymeric biomaterials with different 3D printing methods, as well as intrinsic challenges such as limited printing resolution and rates. Therefore, this review aims to introduce the current state‐of‐the‐art in 3D‐printed functional polymeric health‐related devices. It begins with an overview of the landscape of 3D printing techniques, followed by an examination of commonly used polymeric biomaterials. Subsequently, examples of 3D‐printed biomedical devices are provided and classified into categories such as biosensors, bioactuators, soft robotics, energy storage systems, self‐powered devices, and data science in bioplotting. The emphasis is on exploring the current capabilities of 3D printing in manufacturing polymeric biomaterials into desired geometries that facilitate device functionality and studying the reasons for material choice. Finally, an outlook with challenges and possible improvements in the near future is presented, projecting the contribution of general 3D printing and polymeric biomaterials in the field of healthcare.

Abstract Background Ventricular tachycardia (VT) is a life-threatening arrhythmia that can complicate structural heart disease. While catheter ablation is effective in treating this condition, the recurrence of VT after the procedure continues to be a concern. Consequently, there is a need for a reliable system to evaluate the likelihood of arrhythmia recurrence following an ablation. Objective To predict recurrence or repeat ablation after a VT catheter ablation procedure using machine learning (ML) models. Methods We conducted a single-center, retrospective study of all patients undergoing catheter ablation for scar-related VT between 2012 and 2022. Data collected included demographics, comorbidities, medications, relevant laboratory abnormalities, electrocardiograms, echocardiograms, detailed procedural characteristics, and outcomes. Python version 3.8.5 for exploratory data analysis (EDA) and visualization. Using six different ML models from the training set (90:10 split), we used 34 variables to predict the primary outcome, including VT recurrence or repeat catheter ablation. The accuracy of these models was compared using ROC curves based on their performance on the test set. Results Out of 508 VT ablation procedures, 261 experienced a recurrence. Support Vector Classifier (SVM) performed the best, having an AUC of 0.73, followed by logistic regression at 0.69 (Figure A). SVM yielded sensitivity, specificity, positive and negative predictive values of 0.73, 0.73, 0.79, and 0.67, respectively. The F1 score was 0.70. Among the factors with the highest feature importance in the model, the most influential variable was the proceduralist’s experience level, followed by QRS width at baseline, LVEF, and patient’s age (Figure B). Conclusion Our model can predict recurrent VT after ablation with reasonable accuracy, outperforming the existing clinical risk scores significantly. Larger training sample sizes will help achieve more robust ML models and improve predictive accuracy further.Figure A: ROC curve depicting the AUROCB. Feature importance graph

Background: Cardiometabolic disease (CMD) disproportionately affects African American/Black (AA) and Latino communities. CMD disparities are exacerbated by their underrepresentation in clinical trials for CMD treatments including nutritional interventions. The study aimed to (1) form a precision nutrition community consultant panel (PNCCP) representative of Latino and AA communities in Los Angeles to identify barriers and facilitators to recruitment and retention of diverse communities into nutrition clinical trials and (2) develop culturally informed strategies to improve trial diversity. Methods: A deliberative community engagement approach was used to form a PNCCP for the Nutrition for Precision Health (NPH) trial, part of the of the All of Us research initiative. The PNCCP included individuals that provide services for Latino and AA communities who met during 11 virtual sessions over 1 year. Discussion topics included enhancing recruitment and cultural acceptance of the NPH trial. We summarized CCP recommendations by theme using an inductive qualitative approach. Results: The PNCCP included 17 adults (35% AA, 47% Latino). Four thematic recommendations emerged: reducing structural barriers to recruitment, the need for recruitment materials to be culturally tailored and participant-centered, community-engaged trial recruitment, and making nutrition trial procedures inclusive and acceptable. We outlined the study response to feedback, including the constraints that limited implementation of suggestions. Conclusion: This study centers community voices regarding the recruitment and retention of AA and Latino communities into a nutrition clinical trial. It highlights the importance of community engagement early on in protocol development and maintaining flexibility to enhance inclusion of diverse communities in nutrition clinical trials.

As a treatment for the widely spread cardiovascular diseases (CVD), bypass vascular grafts have room for improvement in terms of mechanical property match with native arteries. A 3D‐printed nozzle is presented, featuring unique internal structures, to extrude artificial vascular grafts with a flower‐mimicking geometry. The multilayer‐structured graft wall allows the inner and outer layers to interfere sequentially during lateral expansion, replicating the nonlinear elasticity of native vessels. Both experiment and simulation results verify the necessity and benefit of the flower‐mimicking structure in obtaining the self‐toughening behavior. The gelation study of natural polymers and the utilization of sacrificial phase enables the smooth extrusion of the multiphase conduit, where computer‐assisted image analysis is employed to quantify manufacturing fidelity. The cell viability tests demonstrate the cytocompatibility of the gelatin methacryloyl (GelMA)/sodium alginate grafts, suggesting potential for further clinical research with further developments. This study presents a feasible approach for fabricating bypass vascular grafts and inspires future treatments for CVD.

Abstract Many patients in the emergency department present with signs and symptoms that arouse concern for sepsis; however, other explanations are also possible. There are currently no rapid tests used in clinical practice that reliably distinguish the presence of a bacterial or viral infection vs. a non-infectious etiology and can predict a patient’s likelihood to decompensate. The diagnostic and prognostic uncertainty in “gray zone” patients complicates the decision to begin therapy as clinicians need to balance the risk of withholding therapy vs. the risk of the therapy itself (e.g., overtreatment with antibiotics and hospitalization, which is costly, potentially harmful, and contributes to antibiotic resistance). The TriVerity™ Test uses isothermal amplification and machine-learning algorithms to quantify and interpret mRNA expression levels to determine both likelihood of bacterial infection, viral infection, or no infection, and whether the patient will likely require one or more critical interventions within 7 days. The three scores each fall into one of five interpretation bands ranging from Very high to Very low. Testing takes approximately 30 minutes using the proprietary Myrna™ Instrument with an operator hands-on-time of under one minute. We enrolled 1,222 patients from 22 emergency departments (ED) to validate the performance of the TriVerity Test. Patients were treated as per local standard of care and were followed for 28 days. Bacterial and viral TriVerity results were validated against clinically adjudicated infection status; the illness severity TriVerity result was validated against the need for at least one critical interventions within 7 days. The bacterial TriVerity result had high AUROC for the diagnosis of bacterial infection (0.83; 80% CI 0.81–0.85) and divided bacterial infection likelihood scores into five interpretation bands with increasing likelihood ratios of infection ranging from Very low (LR- 0.08, 80% CI 0.06–0.11) to Very high (LR + 8.04, 80% CI 5.72–11.78). The AUROC for the bacterial TriVerity result was significantly higher compared to AUROCs for C-reactive protein, procalcitonin or white blood cell count. Similarly, the viral TriVerity score showed high AUROC for the diagnosis of viral infection (0.91; 80% CI 0.90–0.93) and likelihood ratios from Very low (LR- 0.09, 80% CI 0.05–0.14) to Very high (LR + 40.93; 80% CI 29.11–79.23). The TriVerity Illness Severity score showed a high AUROC for the prediction of illness severity (0.77; 80% CI 0.77–0.81) with scores divided into five interpretation bands with increasing likelihood ratios ranging from Very low (LR- 0.22; 80% CI 0.14–0.33) to Very high (LR + 11.33; 80% CI 7.31–17.00). TriVerity illness severity results allowed marked re-classification of the risk for “ICU-level care” as compared to clinical assessment (qSOFA scores) alone. In conclusion, TriVerity provides rapid, highly accurate and actionable results for the diagnosis and prognosis of patients with suspected acute infection and/or sepsis, supporting a major unmet medical need. TriVerity may improve personalized management of patients with suspected acute infections and suspected sepsis for improved overall healthcare outcomes.

BACKGROUND AND OBJECTIVES: First-line therapy for most intracranial dural arteriovenous fistulas (dAVFs) is endovascular embolization, but some require microsurgical ligation due to limited endovascular accessibility, anticipated lower cure rates, or unacceptable risk profiles. We investigated the most common surgically treated dAVF locations and the approaches and outcomes of each. METHODS: The Consortium for Dural Arteriovenous Fistula Outcomes Research database was retrospectively reviewed. Patients who underwent dAVF microsurgical ligation were included. Patient demographics, angiographic information, surgical details, and postoperative outcomes were collected. The 5 most common surgically treated dAVF locations were analyzed about used surgical approaches and postoperative outcomes. Univariate analyses were performed with statistical significance set at a threshold of P < .05. RESULTS: In total, 248 patients in the Consortium for Dural Arteriovenous Fistula Outcomes Research database met inclusion criteria. The 5 most common surgically treated dAVF locations were tentorial, anterior cranial fossa (ACF), transverse-sigmoid sinus (TSS), convexity/superior sagittal sinus (SSS), and torcular. Most tentorial dAVFs were approached using a suboccipital, lateral supracerebellar infratentorial approach (39.3%); extended retrosigmoid approach (ERS) (25%); or posterior subtemporal approach (19.6%). All ACF dAVFs used a subfrontal approach; 5.3% also included an anterior interhemispheric approach. Most TSS dAVFs were ligated via ERS (31.3%) or subtemporal (31.3%) approaches. All convexity/SSS dAVFs used an interhemispheric approach. All torcular dAVFs used the suboccipital, lateral supracerebellar infratentorial approach, with 10.5% undergoing simultaneous ERS craniotomy. Angiographic occlusion rates after microsurgery were 85.5%, 100%, 75.8%, 79.2%, and 73.7% for tentorial, ACF, TSS, convexity/SSS, and torcular dAVFs, respectively ( P = .02); the permanent neurological complication rates were 1.8%, 2.6%, 9.1%, 0%, and 0% ( P = .31). There were no statistically significant differences in development of complications ( P = .08) or Modified Rankin Scale at the last follow-up ( P = .11) by fistula location. CONCLUSION: Although endovascular embolization is the first-line treatment for most intracranial dAVFs, surgical ligation is an important alternative. ACF and tentorial fistulas particularly demonstrate high rates of postoperative obliteration.