Institutional Review Board Protocol Research Articles

Addressing the Evidence Gap in Aneurysmal Subarachnoid Hemorrhage: The Need for a Pragmatic Randomized Trial Platform.

Aneurysmal subarachnoid hemorrhage (aSAH) occurs less often than other stroke types but affects younger patients, imposing a disproportionately high burden of long-term disability. Although management advances have improved outcomes over time, relatively few aSAH treatments have been tested in randomized clinical trials (RCTs). One lesson learned from COVID-19 is that trial platforms can facilitate the efficient execution of multicenter RCTs even in complex diseases during challenging conditions. An aSAH trial platform with standardized eligibility criteria, randomization procedures, and end point definitions would enable the study of multiple targeted interventions in a perpetual manner, with treatments entering and leaving the platform based on predefined decision algorithms. An umbrella institutional review board protocol and clinical trial agreement would allow individual arms to be efficiently added as amendments rather than stand-alone protocols. Standardized case report forms using the National Institutes of Health/National Institute of Neurological Disorders and Stroke common data elements and general protocol standardization across arms would create synergies for data management and monitoring. A Bayesian analysis framework would emphasize frequent interim looks to enable early termination of trial arms for futility, common controls, borrowing of information across arms, and adaptive designs. A protocol development committee would assist investigators and encourage pragmatic designs to maximize generalizability, reduce site burden, and execute trials efficiently and cost-effectively. Despite decades of steady clinical progress in the management of aSAH, poor patient outcomes remain common, and despite the increasing availability of RCT data in other fields, it remains difficult to perform RCTs to guide more effective care for aSAH. The development of a platform for pragmatic RCTs in aSAH would help close the evidence gap between aSAH and other stroke types and improve outcomes for this important disease with its disproportionate public health burden.

Wellness Activities, Stress, and Academic Performance in Medical Students.

Medical student wellness has a range of effects from academic performance to tragic mortality. Many factors correlate with academic performance, including study environments, faculty support, research participation, and student attitude. Its relationship with student stress and wellness demonstrates mixed results. This study hopes to help clarify these resultsand will also assess the interplay of these factors in relation to the pre-clerkship and clerkship phases of medical school. This retrospective descriptive study was conducted using a de-identified database from 2017 to 2023, provided per an Institutional Review Board (IRB) protocol. The subjects were the students of the classes of 2021-2027 at the Kirk Kerkorian School of Medicine at UNLV. The database included performance data including semester, clinical subject, and USMLE Step 1 and Step 2 exam scores. Other data included variables relating to self-perceived stress and time spent in wellness activities before medical school and at the end of the pre-clerkship and clerkship phases of medical school. The effects of these variables were calculated with bivariate correlations and independent samples T-tests using cut-off points calculated from the class means of those variables. A total of 361 medical students were included in the study. Students with high wellness time had lower stress levels in both the pre-clerkship and clerkship phases of medical school (5.83 vs. 7.3 p < 0.001* and 5.74 vs. 8.49 p < 0.001*, respectively). Students with low stress levels in the pre-clerkship phase scored 5.81 points higher on the Step 1 exam (p = 0.013*). Clerkship phase stress levels were significantly negatively correlated with all clinical subject exams except for pediatrics. Stress levels in the pre-clerkship and clerkship phases had similar relationships with the second and third semester and Step 2 exams, respectively, although not statistically significant. Wellness activity time did not have a significant relationship with academic performance. Stress levels had significant negative relationships with many medical school exams. Although wellness activity time did not have a direct relationship with academic performance, its relationship with stress levels can allude to an indirect effect on academic performance. This, along with fending off burnout and stress, are reasons why medical student wellness should be a priority for medical schools, faculty, and their students.

Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era.

e21522 Background: Despite the drastic improvement in survival of patients with metastatic melanoma from immune checkpoint inhibitors (ICIs), almost half of patients still die from their disease. Factors surrounding death including mechanisms of death, sites of disease, and settings of death remain poorly described. A better understanding of these factors is paramount to optimize management for these patients. Methods: A retrospective observational cohort study was performed for patients age &gt; 18 who died after treatment for advanced melanoma with anti-PD1 therapy or ipilimumab + nivolumab (Ipi/Nivo) at Yale Cancer Center (YCC) between 1/2009 and 6/2023. Primary outcome was cause of death. Statistical analyses were performed with Stata SE, version 15.0 (StataCorp, College Station, TX). This study was approved by the Yale Institutional Review Board (Protocol #2000034631). Results: Overall, 287 patients with melanoma who received ICIs were documented to be deceased; 183 met inclusion criteria. Median time from metastatic diagnosis to death was 16.1 mos (range 0.3 to 135.1 mos). Median age at death was 70 (range 22-101), 62.8% were male, and 90.2% were white. Most patients (52.5%) received Ipi/Nivo first line, and 79.8% of patients received both anti-PD1 and anti-CTLA4 treatment at some point. The median number of metastatic sites at death was 4 (range 0-13). The majority (90.1%) of patients with measurable disease had multi-system involvement of melanoma. Eleven patients had no evidence of disease at death and died due to non-melanoma causes. The most common sites of metastatic disease at death were distant lymph nodes (62.8%), lung (57.9%), liver (50.8%), brain (38.8%), and bone (37.7%). In total, 80.3% (147/183) experienced hospitalization within 3 months prior to death or hospice enrollment. Most died in the hospital (31.7%) or while enrolled in hospice (31.2% inpatient vs. 29.4% home). Overall, 10.9% of patients had survival &gt; 5 years after metastatic diagnosis; 76.2% of long-term survivors died due to melanoma. Of 174 patients with evaluable causes of death, 87.9% of deaths were due to melanoma (Table 1). Patients with pleural metastases were more likely to die of respiratory failure (p = 0.036, OR 2.41 95% CI 1.06-5.50). Conclusions: The majority of deaths were a consequence of metastatic melanoma, with the most common causes including FTT, respiratory failure, and infection. [Table: see text]

Families in transition (FIT) study protocol: feasibility, acceptability and preliminary effects of a group-based parent training in parents of youth in psychiatric residential treatment

IntroductionAlthough adolescents make treatment gains in psychiatric residential treatment (RT), they experience significant difficulty adapting to the community and often do not sustain treatment gains long term. Their parents are...

Versatility of Single Port Retroperitoneal Low Anterior Access: Early Outcomes in Multiple Procedures.

Purpose: This study aimed to assess early outcomes of the single port (SP) robotic low anterior access (LAA) for all upper urinary tract surgeries. In addition, it aimed to explore the impact of clinical factors, notably Body Mass Index (BMI), on post-operative outcomes and length of hospital stay. Materials and Methods: Overall, 76 consecutive patients underwent SP robotic surgery with LAA involving all upper urinary tract pathologies, with data collected prospectively. Baseline characteristics, intra- and post-operative outcomes, pain levels, and opioid use were analyzed. Statistical methods, including logistic regression and locally weighted scatterplot smoothing analysis, were used to assess same-day discharge (SDD) predictors and the association between BMI and SDD probability. According to the Institutional Review Board (IRB) protocol, only data recorded in our electronic medical record system was included. Results: Ten different procedures were performed with LAA, with no need for conversion to open surgery and complication rates in line with the literature (30 days: 5%, 90 days: 6.6%). Notably, 77.6% of patients were discharged on the same day. A significant association was found between BMI and prolonged hospital stay, particularly in obese patients (BMI ≥30 kg/m2). Post-operative pain was generally low (median VAS: 4), with over 70% discharged without opioid prescriptions. Conclusions: The novel LAA is a versatile approach for various upper urinary tract surgeries, including in obese patients. While achieving satisfactory post-operative outcomes, increased BMI correlated with a reduced likelihood of SDD. Further studies, including larger cohorts and multicenter collaborations, are warranted to explore anesthesiologic management and validate these findings.

AI-Powered Web Applications for Enhanced Clinical, Research, and Professional Development

Introduction: The rapid growth of technology in the field of anesthesiology offers unique opportunities to leverage artificial intelligence (AI) for enhancing clinical, research, and administrative operations. Our team, consisting of anesthesiologists and data scientists, sought to develop a suite of web applications using generative AI to address specific challenges faced by anesthesiology departments. Objective: To design, develop, and evaluate the feasibility of a range of AI-powered web applications tailored for anesthesiologists to streamline research feasibility, literature searches, protocol drafting, text simplification, work promotion, grant writing, professional advancement, and secure communication. AI Tools developed: Data Feasibility Analysis: AI-assisted search of descriptions and schemas of multiple data warehouses to assess the feasibility of various clinical and research ideas. AI-Powered PubMed Search: AI-assisted search to effciently navigate and extract relevant publications from PubMed, including summarizing the literature found. IRB Protocol Generation: Automated drafting process for Institutional Review Board (IRB) protocol forms, ensuring adherence to regulatory standards. Text Simplification: Tool to distill complex clinical, research, or regulatory text to an 8th-grade reading level, enhancing accessibility — e.g., for patient consent forms. Work Promotion and Amplification: drafts blog posts, “tweets,” and layperson summaries of research abstracts. NIH Grant Drafting: Drafts Specific Aims page and Research Strategy sections for National Institutes of Health (NIH) style applications, ensuring compliance and coherence. Professional Advancement Assistance: Drafts Promotion &amp; Tenure portfolios and letters of recommendations Secure AI Conversations: Integrated generative AI technology in an encrypted and secured platform, safeguarding sensitive information. Conclusions: The suite of AI-powered web applications, developed in collaboration between anesthesiologists and data scientists, showcases potential in enhancing the effciency and impact of various processes integral to anesthesiology research. The integration of these tools into daily operations can potentially revolutionize how anesthesiologists engage with research, patient care, professional development, and communication. Future endeavors will focus on rigorous validation and widespread deployment to harness the full potential of these innovations. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

128 Resident training in research fundamentals using an online, asynchronous course

OBJECTIVES/GOALS: Scholarly activity is a key component of most residency programs. To establish fundamental research skills and fill gaps within training curricula, we developed an online, asynchronous set of modules to introduce trainees to various topics that are germane to the conduct of research and evaluated its effectiveness in resident research education. METHODS/STUDY POPULATION: Research 101 was utilized by residents at the Brookdale Hospital Medical Center in Brooklyn, NY. Resident knowledge, confidence, and satisfaction were assessed using pre- and post-module surveys with 5-point Likert scaled questions, open-ended text responses, and a final quiz. RESULTS/ANTICIPATED RESULTS: Pre-module survey results indicated that residents were most confident with the Aligning expectations, Introduction to research, and Study design and data analysis basics modules and least confident with the Submitting an Institutional Review Board (IRB) protocol at UC and Presenting your summer research modules. Post-module survey responses increased significantly compared to pre-module results for all modules and learning objectives (p&lt;0.0001). “This module met my needs” was endorsed 91.4% of the time. A final quiz of 25 multiple choice questions resulted in a median score of 23. Content analysis of open-ended post-module survey responses identified multiple strengths and opportunities for improvement in course content and instructional methods. DISCUSSION/SIGNIFICANCE: These data demonstratethat residents can benefit from completion of Research 101, as post-module survey scores were significantly higher than pre-module survey scores for all modules and questions, and final quiz scores were high and highlighted opportunities for additional resident learning.

92 Honest Broker Tool to Automate Data Extraction from Clinical Research Data Warehouse

OBJECTIVES/GOALS: To describe an Honest Broker (HB) tool and workflow integrated with the Institutional Review Board (IRB) to automate requests, approvals and delivery of both de-identified and identified data extractions from a clinical research data warehouse (CRDW). METHODS/STUDY POPULATION: The HB tool has predefined domain tables and is closely integrated IRB for quick and easy review and approval. Investigators can access patient data using query tools, barcodes from biospecimens or build a query in TriNetX and provide the patient list as an input for the HB tool. For de-identified data extraction, the required data domain tables and date ranges can be selected and submitted in the HB tool. For identified data extractions, investigators with an approved IRB protocol can enter the protocol number and the approved date range in the HB tool. This request is automatically forwarded to the IRB for review. RESULTS/ANTICIPATED RESULTS: For de-identified data extraction, an email alert is automatically sent to the investigator once the data extract is completed. For identified data extraction, if IRB approves the request, an HB is immediately notified to release the data. Data release triggers two emails to the investigator: (1) a link to an encrypted zipped file with the requested data, and (2) a password to unlock the encrypted file. If the request is denied, the IRB sends an email to the investigator with the reason for denial and options for remediation. The entire HB workflow is accomplished in a secure environment with an audit trail from the initial data request to data download by the investigator. Since the launch of the HB tool, the time from data request to delivery is approximately an hour for deidentified data and 24 hrs for identified data. DISCUSSION/SIGNIFICANCE: The HB tool has increased successful data delivery in support of publications, grant submissions, and clinical trial recruitment. Optimization of data extraction from the CRDW through automation and integration with the IRB can minimize interaction with data analysts and IRB staff, thus accelerating the conduct of clinical research.

Abstract 5492: Spatial organization and cellular composition of immunity hubs in human colorectal cancer

Abstract Background: Among colorectal cancer (CRC) tumors, mismatch repair deficient (MMRd) tumors have more immunogenic neo-antigens, hence more cytotoxic T-cell mediated anti-tumor immunity than mismatch repair proficient (MMRp) tumors. Previously1, we transcriptionally profiled over 300,000 cells from 62 MMRd and MMRp CRC tumors and found an MMRd-unique network of immunologically active transcriptional states enriched in interferon-stimulated genes (ISGs). With 4-color imaging, we showed that this program arises from spatially organized hubs of at least 3 cell types: IFNã-secreting T and interferon-responsive CXCL9/10/11+ myeloid and tumor cells. To characterize the breadth of cells involved in tumor immunity hubs, we must simultaneously measure the expression of 100s of genes in situ. Methods: To describe the cellular composition, structural organization and intercellular spatial interactions of these immunity hubs, we profiled primary untreated resection specimens from 17 CRC donors (n=12 MMRd, 5 MMRp) using multiplexed error-robust FISH (MERFISH) mRNA microscopy. Efforts were made to sample both the tumor body and the invasive border of the tumor. We designed a panel of 479 genes to capture key transcriptional programs from our single-cell atlas1. We wrote analytical pipelines to segment transcripts into cells, select high-quality cells, and organize cells into distinct zones in tissue. To leverage the rich information in the scRNA-seq atlas1, we designed a robust label transfer analysis to assign cell state labels to MERFISH cells by comparison to scRNAseq cells. Results: We profiled 7.5 million high quality MERFISH cells across 21 CRC tissue sections and labeled the cells into 7 major lineages: 63.19% epithelial, 22.52% stromal, 7.75% myeloid, 3.72% T/NK/ILCs, 1.45% plasma, 1.2% B, and 0.17% mast cells. We visualized the spatial location of these cell types. T cells aggregated into 3 distinct regions of tissue: tertiary lymphoid structures (TLS) outside the tumor, and smaller clusters near the invasive border and in the tumor center. We identified immunity hubs defined by colocalized CXCL9/10/11 expressing cells and T cells near the invasive border and in the center of MMRd tumors. As expected, we found enrichment of CXCL13, IFNG, and ISGs such as CD74 and MHCII genes at these locations. In contrast, we found evidence of CCL17+CCL19+LAMP3+ activated dendritic cells and B cells enriched in the TLS. These results support a distinct composition and localization of immunity hubs in tumors, in contrast to TLS outside tumors. Conclusions: Our study defines the composition, spatial organization, and intercellular interactions of immunity hubs, shedding light on the anti-tumor immune response in CRC. Ethics Approval: Approved by the DF/HCC Institutional Review Board (protocol #02-240).(1) Pelka, K. et al. Spatially organized multicellular immune hubs in human colorectal cancer. Cell 184, 4734-4752.e20 (2021) Citation Format: Mukta G. Palshikar, Maxwell Spurrell, Jack Demaray, Han Chen, Scott Engels, Roopa Madhu, Milan Parikh, Izabella Gazmora, Arnav Mehta, Nicolas Fernandez, Colles Price, Jiang He, Sonia Cohen, Karin Pelka, Nir Hacohen, Jonathan Chen, Ilya Korsunsky. Spatial organization and cellular composition of immunity hubs in human colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5492.

Design and rationale of the Post-Intensive Care Syndrome – paediatrics (PICS-p) Longitudinal Cohort Study

IntroductionAs paediatric intensive care unit (PICU) mortality declines, there is growing recognition of the morbidity experienced by children surviving critical illness and their families. A comprehensive understanding of the adverse...

Abstract B045: Deep genomic and single cell molecular profiles define immunogenic pancreatic cancer

Abstract Background: Most pancreatic cancers (PC) are resistant to immunotherapy and have a poor prognosis with advanced stage (III/IV, 80%). However, recent cancer vaccine trials have demonstrated that long-term host anti-cancer immunity can improve outcomes of patients (pts) with resectable PC (stage I/II, 20%), harboring high-quality neoantigens or select KRAS alterations. It has been proposed that immunogenic PC is a genetically defined subgroup (5-10%), enriched by hypermutated PC with DNA-damage repair deficiencies including homologous repair (HRD) and mismatch repair (dMMR). Until now, comprehensive molecular studies have been mostly conducted in resected PC. Methods: All tissues were collected following an Institutional Review Board (IRB 21-275) protocol at the Memorial Sloan Kettering. Whole-exome from N=78, exome-captured bulk RNA from N=61, and single-nucleus RNA from N=23 biopsy samples of advanced PC were analyzed. Gene set enrichment and digital cytometry, singe base substitution (SBS) mutational signature, neoantigen, and genomic instability score (GIS) for HRD and immunogenicity were evaluated. Demographics, treatment history, and overall survival (OS) for pts with PC with or without HRD and dMMR were abstracted from the medical record. Results: A total of N=77 WES samples included N=21 core HRD (cHRm: 3 BRCA1, 17 BRCA2, 1 both), N=7 non-core HRD (ncHRm: 3 ATM, 2 CHEK2, 1 RAD50, 1 BARD1), and N=7 dMMR, and N=42 No DDR. N=46 males. Median age 65 years. Median OS (95% confidence interval): 26 months (m) (17-NR) for cHRm, 90m (14-NR) for dMMR, 7.4m (6.8-NR) for ncHRm, and 19m (15-27) for No DDR group. N=49 (63%) pts received first-line platinum chemotherapy. Median tumor mutation burden (TMB-WES): 2 (IQR: 2-3), 35 (30-47), 1 (1-2), and 1, respectively for cHRm, dMMR, ncHRm, and No DDR. TMB-WES significantly higher for dMMR vs. No DDR (95%CI: 35 [30-47] vs 1 [1-2], p=0.001). GIS higher for cHRm vs. No DDR (95%CI: 31 [18-38) vs 14 [9-18], p=0.008). Only two BRCA1m tumors had significant SBS3. N=61 exome captured RNAseq analysis showed cHRm (N=17) vs. No DDR (N=39) had highly enriched gene programs for upregulated immune activity in adaptive immune response (odds ratio [OR]: 0.49, p=1.7e-10), humoral immune response, and T cell activation (OR: 0.44, p=2.7e-8). Digital cytometry showed higher infiltration of gamma delta T cells (p=0.039) and lower regulatory T cells (p=0.001) in cHRm vs. No DDR. 59,771 nuclei were profiled from 23 (16 baseline and 7 follow-ups [5 matched]) biopsy samples from pts with HRD [gBRCA1 (N=3), gBRCA2 (N=14)] and No DDR (N=6). HRD tumors vs. No DDR had higher level of infiltrating CD8+ cytotoxic T cells (p&amp;lt;0.01). Tumors of long-term survivors (&amp;gt; 18m) vs. short-term survivors had significantly lower-level infiltration of macrophages (p&amp;lt;0.01) and Tregs (p=0.05). Conclusions: Our deep genomic and single-cell resolution transcriptomic analyses successfully profiled advanced PC enriched with DDR. HRD and dMMR render PC immunogenic. Further investigations for targeted immunotherapy is warranted. Citation Format: Wungki Park, Shigeaki Umeda, Catherine O'Connor, Haochen Zhang, Roshan Sharma, Allison Richards, Yingjie Zhu, Elias-Ramzey Karnoub, Xin Pei, Anna M. Varghese, Kevin Soares, Alejandro Jimenez Sanchez, Hulya Ozkan Sahin, Kenneth Yu, Vinod P. Balachandran, Joanne Chou, Fergus Keane, David Kelsen, Olca Basturk, Chaitanya Bandlamudi, Marinela Capanu, Tal Nawy, Michael Berger, Ronan Chaligne, Ghassan Abou-Alfa, Jorge S. Reis-Filho, Nadeem Riaz, Dana Pe'er, Christine A. Iacobuzio-Donahue, Eileen M. O'Reilly. Deep genomic and single cell molecular profiles define immunogenic pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B045.

Laughter therapy cardiac rehabilitation in patients with stable coronary artery disease: a randomized clinical trial

Abstract Background Different non-pharmacological strategies have been studied in patients with stable coronary artery disease (CAD). However, the potential benefits of laughter therapy cardiac rehabilitation (LTRehab) for patients with stable CAD have not been fully investigated, especially through randomized clinical trials (RCT). Purpose This study aimed to evaluate the impact of LTRehab on functional capacity, endothelial function, and inflammatory biomarkers in CAD patients. Methods This is a randomized, parallel-design, examiner-blinded, controlled clinical trial conducted from August 2016 to December 2020. Peak oxygen uptake (VO2peak) and flow-mediated dilation (FMD) were measured using maximal cardiopulmonary exercise testing (CPET) and ultrasound, respectively. Inflammatory biomarkers, including interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, vascular cell adhesion molecule (VCAM), and intercellular adhesion molecule (ICAM), were measured. Thirteen patients were assigned to the LTRehab group, who watched two self-selected comedy sessions per week, and thirteen patients to the control group (CG), who watched two neutral documentaries (24 movies per group). Generalized Estimated Equations were used to identify the main factors of Group, Time, and the interaction between Group*Time. The Bonferroni correction was applied to identify differences. P &amp;lt; 0.05 was considered statistically significant. This study was approved by the Institutional Review Board (protocol No. 13-0124). Furthermore, it was conducted in accordance with Resolution no.466/12 of the National Health Council. Results A total of 26 CAD patients (69% male; mean age of 63.58 ± 9.97 years) were included in the study. There was a significant interaction between Group*Time (P&amp;lt;0.01) for VO2peak (LTRehab group: 19.09±0.85 to 21.06±1.00 vs. CG: 23.21±1.74 to 22.24±1.96 mL.kg-1.min-1). There was a mean difference of 1.98±0.45 between times for the LTRehab group with significant Bonferroni correction (P&amp;lt;0.01), but not for the control group (-0.96±0.75, P=0.20). Nitroglycerin-mediated vasodilation (endothelium-independent function) and VCAM showed significant differences in the Time factor (P = 0.02 and P = 0.05, respectively). All CPET tests reached maximal criteria (R&amp;gt;1.10). Conclusion This is the first RCT to evaluate the impact of LTRehab on CAD patients, showing an increase in VO2peak and improvements in endothelium-independent function and inflammatory biomarkers. LTRehab may constitute an effective form of cardiac rehabilitation in this patient population.

Monocyte-to-lymphocyte ratio as predictor of cancer therapy-related cardiotoxicity in patients with breast cancer

Abstract Background Elevated pre-treatment baseline inflammation has been associated with cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer. Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index [SII = (neutrophil × platelets)/ lymphocyte] are inflammation markers easily obtained through of the blood count. Purpose To evaluate the development of CTRCD according to pre-treatment blood inflammatory biomarkers in patients with breast cancer. To evaluate the development of CTRCD in patients with HER2+ early breast cancer according to MLR, NLR, PLR, and SII inflammatory markers obtained from pre-cancer therapy blood count. Methods Prospective cohort study including consecutive female patients ≥ 18 years with HER2+ early breast cancer who consulted at the institution's breast oncology outpatient clinic between march/2019 and march/2022. This study was approved by the Institutional Review Board (protocol No. 2019-0010). Furthermore, it was conducted in accordance with Resolution no.466/12 of the National Health Council. CTRCD: absolute reduction in LVEF &amp;gt; 10% to below 53% (2D-echocardiogram). Survival analysis was performed using Kaplan-Meier curves, compared by the log-rank test, and discrimination ability was evaluated through area under the ROC curve (AUC-ROC). P &amp;lt; 0.05 was considered statistically significant. Results Forty-nine patients (53.3±13.3y) were included and followed up for a median of 13.2 (IQR 25-75%: 10.8-16.1) months. CTRCD was observed in 6 (12.2%) patients. Patients with high blood inflammatory biomarkers had lower CTRCD-free survival (P &amp;lt; 0.050 for all, Figure A-D). MLR showed statistically significant AUC-ROC (0.802; P = 0.017). CTRCD was observed in 27.8% of patients with high MLR vs. 3.2% with low MLR (P = 0.020); negative predictive value was 96.8% (95%CI: 83.3-99.4%). Conclusions In patients with breast cancer, elevated pre-treatment inflammatory markers were associated with increased risk of cardiotoxicity. Among these markers, MLR had good discriminatory performance and high negative predictive value. The incorporation of MLR might improve risk evaluation and selection of patients for follow-up during cancer therapy.Figure (A-D)

Study protocol for NeuroCARE: a randomised controlled trial of a psychological intervention for caregivers of patients with primary malignant brain tumours

IntroductionCaregivers of patients with primary malignant brain tumours experience substantial psychological distress while caring for someone with a progressive, life-limiting neurological illness. However, there are few interventions aimed at addressing...

Vocal Cord Monitoring by Flexible Fiberoptic Laryngoscopy During Thyroid Radiofrequency Ablation.

Introduction: Thermal injury to recurrent laryngeal nerve (RLN) during radiofrequency ablation (RFA) can produce temporary or permanent vocal cord paralysis.1 Hydrodissection with cold 5% glucose of "danger triangle" protects RLN during RFA.2 When RFA is performed under local anesthesia, RLN function is monitored by patients producing vocal sounds.3 Large lesions requiring longer RFAs warrant general sedation where voice cannot be assessed, therefore, an additional technique for RLN protection is advisable. Observation of passive symmetrical vocal cord movements during breathing by laryngeal ultrasonography is useful in assessing vocal cord function4; however, flexible-fiberoptic fibrolaringoscopy (FFL) is gold standard for assessing vocal cord movements,5 anticipating potential RLN damage. We report FFL monitoring during RFA under general sedation on a large thyroid nodule. FFL during RFA may detect RLN irritation and dysfunction if asymmetry in passive vocal cord movements is noted. Should asymmetry appear, RFA operator stops delivering energy and repositions electrode needle. Materials and Methods: Thyroid function tests, blood glucose, creatinine, transaminase, International-Normalized-Ratio, and electrocardiogram were performed. Operating room (OR) layout created sufficient space for ear-nose-throat (ENT) and RFA operators. An examination with a fiberscope camera demonstrated normal vocal cord adduction during phonation and abduction during breathing. The procedure was assisted by an anesthetist administering fentanyl 50 mcg, midazolam 1.5 to 5.0 mg, and propofol infusion 2 mg/(kg·h). General sedation was conducted so that reflexes were attenuated but still observable. Incorporating in OR by an anesthetist who performs general sedation reduces side effects and complications.6 Ultrasonography showed a 34-mL right lobe nodule abutting on the RLN area. After sedation with propofol, the ENT specialist inserted an endoscope until the glottic plane. During calm breathing, vocal cords moved symmetrically. After obtaining anterior nodule hydrodissection from strap and sternocleidomastoid muscles with 10 mL of 2% lidocaine, posterior hydrodissection was achieved by ultrasound-guided administration of 30 mL of 5% cold glucose. Anterior and posterior hydrodissections merged, separating nodule from neck structures. The radiofrequency electrode needle was then inserted into the nodule, initially positioned in inferior nodule portion adjacent to danger triangle previously isolated by hydrodissection. Initial power was 30 watts. Moving-shot technique was used. Results: FFL was performed throughout thyroid RFA. Symmetric vocal cord movements during breathing demonstrated no RLN irritation. FFL monitoring allowed observation of natural reflexive phenomena, including swallowing. Complete nodule ablation was achieved. FFL performed post-RFA confirmed normal vocal cord motility. Conclusions: We report the first-time use of FFL for vocal cord monitoring during RFA. FFL was easily performed by the ENT specialist and well tolerated by the patient. Avoiding danger triangle and precise RFA needle positioning is key in preventing RLN injury. Benign nodules regrow if total ablation is not achieved7 and some authors propose additional procedures to complete ablation8 that obviously incurs costs. Total RFA nodule ablation-assisted FFL monitoring eliminates the need for repetitive RFAs, thus reducing overall treatment costs. Finally, FFL monitoring does not prolong procedure, as it is performed simultaneously with RFA. FFL is a valid technique when used in conjunction with hydrodissection to further prevent RLN thermal injury during RFA, especially indicated for large thyroid nodule ablation and professional voice users. Patient Consent and Permission: The patient provided written consent for FFL monitoring and permission to use his portrayals and ultrasonographic images during RFA. The study was completed in accordance with the Declaration of Helsinki as revised in 2013. Adherence to institutional review board protocols was granted. Disclaimer: Representation of any instrumentation within the video does not indicate any endorsement of the product and/or company by the publisher, the American Thyroid Association, or the authors. No competing financial interests exist. Runtime of video: 9 mins 39 secs.

Intramuscular Electrical Stimulation for the Treatment of Trigger Points in Patients with Chronic Migraine: A Protocol for a Pilot Study Using a Single-Case Experimental Design.

Background and Objectives: Trigger points (TrPs) are prevalent in patients with migraine headaches. Needling interventions targeting TrPs in migraine patients may reduce the intensity and frequency of headaches, yet systematic reviews reveal a lack of robust evidence. Intramuscular electrical stimulation (IMES) is a modality that delivers electrical current into muscles and TrPs, with recent studies suggesting it may amplify the therapeutic effects of dry needling peripherally and centrally. This could be advantageous for patients with migraine and symptomatic TrPs. Materials and Methods: This study will implement a multiple baseline single-case experimental design (SCED). In a clinical setting, a SCED study lends itself to conducting research with only a few patients that each serve as their own controls. In this SCED study, four participants with chronic migraine will be enrolled in a non-concurrent manner and randomized to one of four baseline measurement periods (4, 5, 6 or 7 weeks), leading to four potentially different start dates for each participant in the intervention phase. During the intervention phase, patients will receive five sessions of dry needling with IMES, one session per week for five weeks. The primary outcome measure will be headache frequency, i.e., the reduction in the number of headache days over a one-month period using electronic headache diary data from the Migraine Buddy smartphone application. Secondary outcome measures will be changes in mean migraine pain intensity using a numeric pain rating scale (NPRS), migraine disability using the Migraine Disability Assessment Test (MIDAS), the Headache Impact Test (HIT-6), and changes in selected cervical musculoskeletal impairments including pressure pain thresholds (PPTs) over TrPs, the craniocervical flexion test (CCFT), and cervical active range of motion (AROM). Primary and secondary outcome measures will be analyzed separately using both visual and statistical analyses. Results: Actively recruiting participants. This project was approved by the Mass General Brigham Institutional Review Board (protocol #2023P000931) and is registered with ClinicalTrials.gov (NCT05893914). Conclusions: This study will seek to determine the effects of a five-week intervention period of IMES to TrPs in the posterior cervical muscles of subjects with chronic migraine.

Study protocol for data to suppression (D2S): a cluster-randomised, stepped-wedge effectiveness trial of a reporting and capacity-building intervention to improve HIV viral suppression in housing and behavioural health programmes in New York City

IntroductionWith progress in the ‘diagnose’, ‘link’ and ‘retain’ stages of the HIV care continuum, viral suppression (VS) gains increasingly hinge on antiretroviral adherence among people with HIV (PWH) retained in...

Gender Differences in Research Productivity of Academic Physicians Before and During the COVID-19 Pandemic.

Objective: The gendered impact of the COVID-19 on scientific productivity has been primarily studied in nonclinical academic fields. We investigated the gendered effect of the pandemic on diverse measures of research participation among physician faculty, who experienced an increase in clinical duties concomitant with pandemic-era challenges to research. Materials and Methods: Physician faculty employed in both 2019 (prepandemic) and 2021 (pandemic era) were identified at one U.S. medical school. Annual outcomes included scientific publications, Institutional Review Board (IRB)-approved protocols, and extramural funding submissions (funding data were unavailable for 2019). Mixed-effects Poisson regression models compared the pandemic impact by gender. Results: The study included 105 women and 116 men, contributing to 122 publications, 214 IRB protocols, and 99 extramural funding applications. Controlling for potential confounders such as faculty rank and track (tenure vs. nontenure), women's publication count increased by 140% during the pandemic (95% confidence interval [CI]: +40% to +310%, p = 0.001) but was unchanged among men (95% CI: -30% to +50%; p > 0.999). The number of IRB protocols decreased from 2019 to 2021, but to a greater extent among men than women. In 2021, there was no gender difference in the number of extramural funding submissions. Conclusions: Among physician faculty at our medical school, women achieved parity with men on multiple measures of scholarly activity, and women's research productivity outpaced that of men in the same faculty track and rank. Targeted initiatives to support research among women faculty, junior investigators, and clinical investigators may have helped avert exacerbation of prepandemic gender disparities in research participation.

123 Introducing trainees to research using an online, asynchronous course

OBJECTIVES/GOALS: Research is an important aspect of many students’ training. However, most trainees do not complete a scholarly project, and formal research training is rarely included in a degree program’s curriculum. Thus, we developed an online, asynchronous series of modules to introduce trainees to multiple topics that are relevant to the conduct of research. METHODS/STUDY POPULATION: Research 101 was utilized by first year medical students and undergraduate students conducting mentored research projects at the University of Cincinnati College of Medicine. Students’ knowledge, confidence, and satisfaction were assessed using pre- and post-module surveys with 5-point Likert scaled questions, open-ended text responses, and a final quiz. RESULTS/ANTICIPATED RESULTS: Pre-module survey results showed that learners were most confident with the Conducting a literature search and Race and racism in medicine modules and least confident with the Submitting an Institutional Review Board (IRB) protocol at UC module. Post-module survey responses were significantly increased compared to pre-module results for all modules and questions (p &lt; 0.0001). The response to The content of this module met my needs was endorsed across all modules (84.9% yes responses). A final quiz of 25 multiple choice questions covering content from all required modules was completed by 92 students who had a median score of 21 (range: 15 to 25). DISCUSSION/SIGNIFICANCE: These data demonstrate significant learning resulting from completion of Research 101, as post-module survey scores were significantly higher than pre-module survey scores for all modules and questions. Final quiz scores were positive but also highlighted opportunity for additional student learning and will guide evolution of future modules.

Study design and methods of the Wells and Enteric disease Transmission (WET) Trial: a randomised controlled trial

IntroductionThe burden of disease attributed to drinking water from private wells is not well characterised. The Wells and Enteric disease Transmission trial is the first randomised controlled trial to estimate...