Citations

AbstractCancer and its treatment produce deleterious symptoms across the phases of care. Poorly controlled symptoms negatively affect quality of life and result in increased health-care needs and hospitalization. The Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium was created to develop 3 large-scale, systematic symptom management systems, deployed through electronic health record platforms, and to test them in pragmatic, randomized, hybrid effectiveness and implementation trials. Here, we describe the IMPACT Consortium’s conceptual framework, its organizational components, and plans for evaluation. The study designs and lessons learned are highlighted in the context of disruptions related to the COVID-19 pandemic.

Introduction: Obesity and hypertension (HTN) are highly prevalent comorbid risk factors for heart failure with preserved ejection fraction (HFpEF). Obesity and HTN independently increase sympathetic nervous activity and impair muscle blood flow during exercise. Previous work has reported attenuated limb blood flow in patients with HFpEF; however, these findings were compared to controls with dissimilar comorbidities and during small muscle mass exercise. It is unclear if HFpEF alters muscle blood flow responses independent of the obesity- and HTN-mediated alterations. Hypothesis: We hypothesized the muscle blood flow response during cycling would be lower in HFpEF patients than age, sex, BMI, and HTN matched controls (CTL). Methods: HFpEF patients (n=14, 9M/5W, 71±7yrs, 32±4 kg/m 2 ) and CTL (n=12, 8M/4W, 69±7yrs, 31±4 kg/m 2 ) performed an incremental cycling test. Blood pressure was measured by manual sphygmomanometry, cardiac output (Q) by open-circuit acetylene wash-in technique, and systemic vascular resistance (SVR) was calculated. Vastus lateralis blood flow index (BFI) was measured by near-infrared spectroscopy and indocyanine green dye injections and venous norepinephrine concentration was measured. Changes from rest to 40 W of the incremental test are reported. Results: Resting Q, mean arterial pressure, SVR, and venous norepinephrine concentration were not statistically different between groups (p>0.18). From rest to 40 W, the increases in Q (CTL: 3.9±0.8 vs. HFpEF: 3.6±0.7 L/min), mean arterial pressure (CTL: 5.7±2.7 vs. HFpEF: 6.6±6.1 mmHg), and SVR (CTL: -7.3±2.1 vs. HFpEF: -6.0±2.0 mmHg/L/min) were not statistically different between groups (all, p>0.13). The HFpEF group had smaller increases in vastus lateralis BFI at 40 W compared to CTL (CTL: 7.2±3.6 vs. HFpEF: 4.2±2.6 fold-increase from rest) (p=0.02). The HFpEF group had greater increases in venous norepinephrine concentration from rest to 40 W than CTL (CTL: 164±216 vs. HFpEF: 377±247 pg/mL) (p=0.05). Conclusions: Our findings suggest that, compared to age, sex, BMI, and HTN matched controls, patients with HFpEF have an impaired locomotor muscle blood flow response during submaximal cycling exercise likely due to higher locomotor muscle vascular resistance.

Background Percutaneous cement discoplasty (PCD) is a minimally invasive procedure. We aim to explore the efficacy and indication(s) of PCD in patients with degenerative disc disease (DDD). Methods The search was conducted across Ovid MEDLINE, Ovid Embase, and PubMed. Data on study design, patient demographics, pre- and post-procedure Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) scores, and complications were extracted. Inclusion criteria focused on adult patients with degenerative spinal diseases treated with cement discoplasty. The overall effect size was evaluated using a forest plot, and heterogeneity was assessed using the I 2 statistic and chi-squared test. Results The search strategy yielded six studies, which included 336 patients (73.8% female, 26.2% male) with a mean average age of 74.6 years. VAS scores were reported in all studies, showing a significant difference between pre- and post-PCD pain scores (Weighted Mean Difference [WMD]: -3.45; 95% CI: -3.83, -3.08; I 2 = 15%; P < .001). ODI scores were reported in 83% of studies, with a significant difference between pre- and post-PCD scores (WMD: -22.22; 95% CI: -25.54, -18.89; I 2 = 61%; p < .001). Complications reported included infections, thrombophlebitis, vertebral fractures, disc extrusion, and the need for further operations. Conclusions The analysis showed clinically significant improvements in pain and functional disability based on VAS and ODI scores. However, due to methodological limitations and a high risk of bias, the validity and generalizability of the findings are uncertain. Despite these issues, the results provide preliminary insights into PCD's potential efficacy and can guide future research to address current limitations.

Background Ovarian cancer (OC), a highly lethal cancer in women, has a 48% 5-year overall survival rate. Prior studies link the presence of IL-17 and Th17 T cells in the tumor microenvironment to improved survival in OC patients. To determine if Th17-inducing vaccines are therapeutically effective in OC, we created a murine model of Th17-inducing dendritic cell (DC) (Th17-DC) vaccination generated by stimulating IL-15 while blocking p38 MAPK in bone marrow-derived DCs, followed by antigen pulsing. Methods ID8 tumor cells were injected intraperitoneally into mice. Mice were treated with Th17-DC or conventional DC (cDC) vaccine alone or with immune checkpoint blockade (ICB). Systemic immunity, tumor associated immunity, tumor size and survival were examined using a variety of experimental strategies. Results Th17-DC vaccines increased Th17 T cells in the tumor microenvironment, reshaped the myeloid microenvironment, and improved mouse survival compared with cDC vaccines. ICB had limited efficacy in OC, but Th17-inducing DC vaccination sensitized it to anti-PD-1 ICB, resulting in durable progression-free survival by overcoming IL-10-mediated resistance. Th17-DC vaccine efficacy, alone or with ICB, was mediated by CD4 T cells, but not CD8 T cells. Conclusions These findings emphasize using biologically relevant immune modifiers, like Th17-DC vaccines, in OC treatment to reshape the tumor microenvironment and enhance clinical responses to ICB therapy.

Abstract Closed-loop direct brain stimulation is a promising tool for modulating neural activity and behavior. However, it remains unclear how to optimally target stimulation to modulate brain activity in particular brain networks that underlie particular cognitive functions. Here, we test the hypothesis that stimulation’s behavioral and physiological effects depend on the stimulation target’s anatomical and functional network properties. We delivered closed-loop stimulation as 47 neurosurgical patients studied and recalled word lists. Multivariate classifiers, trained to predict momentary lapses in memory function, triggered the stimulation of the lateral temporal cortex (LTC) during the study phase of the task. We found that LTC stimulation specifically improved memory when delivered to targets near white matter pathways. Memory improvement was largest for targets near white matter that also showed high functional connectivity to the brain’s memory network. These targets also reduced low-frequency activity in this network, an established marker of successful memory encoding. These data reveal how anatomical and functional networks mediate stimulation’s behavioral and physiological effects, provide further evidence that closed-loop LTC stimulation can improve episodic memory, and suggest a method for optimizing neuromodulation through improved stimulation targeting.

572 Background: The DEFeNDR (Decreasing the burden of Febrile Neutropenia through Dynamic RPM) program leverages in-home technology and centralized nurse monitoring to facilitate ambulatory management as an alternative to hospital-based care for cancer patients with neutropenic fever (NF). The objective of this study is to assess 30-day care utilization outcomes and patient satisfaction at 12 months after program implementation. Methods: Adult cancer patients hospitalized with NF were assessed daily for DEFeNDR program eligibility including MASCC score ≥21 (per ASCO guidelines) and no cellular therapy (CAR-T, BMT) in the prior 100 days. Patients agreeing to participate in the 30-day program received a cellular-enabled tablet with pre-connected devices for twice-daily vital signs and symptom assessments. Patient generated data were EHR-integrated in real-time. Embedded decision trees facilitated alerts for adverse trends. Virtual RPM nurses responded to alerts and utilized predefined care pathways. The primary endpoint was the mean proportion of evaluable days spent inpatient (mPEDI) within 30 days of eligibility comparing those who participated in the program (RPM) with those who declined (no RPM). Results: Of 85 eligible patients, 62 were offered DEFeNDR participation. Of those, 34 (54.8%) participated and 28 (45.2%) declined. Baseline characteristics and care utilization outcomes are summarized in Table 1. RPM patients experienced significantly lower mPEDI compared with unmonitored patients [5.1% (Standard Error [SE], 1.9%) vs 12.4% (SE, 2.1%); Wilcoxon Rank Sums p-value, 0.032]. RPM patients also experienced a trend toward fewer total hospital days and lower 30-day readmission rate, as well as shorter mean length of stay and lower rate of ICU utilization when readmitted. Non-visit care activities (EHR clinical communications, documentation, and patient messaging) were decreased from pre-hospital baseline for 58.8% of RPM patients versus 46.6% of those unmonitored. All RPM patients completing a patient satisfaction survey (n=9) indicated that they would recommend the program to patients with a similar condition. Conclusions: Cancer patients with NF participating in the DEFeNDR program experienced a significant reduction in mPEDI and care utilization compared with those who declined. Further studies are warranted to assess comparative effectiveness of this model vs usual care.[Table: see text]

435 Background: Assessing tobacco use and providing cessation support is recommended by the American Society for Clinical Oncology (ASCO). As part of the National Cancer Institute Cancer Center Cessation Initiative, we established an electronic health record based "opt-out" approach to refer patients to tobacco treatment specialists. However, the role of oncologists in contributing to the “opt-out” approach to patients has not been explored. We tested the hypothesis that a multi-component educational program for oncologists would increase the proportion of patients who completed tobacco treatment appointments. Methods: As a quality improvement initiative, oncology providers at the Rochester Mayo Clinic Cancer Center were educated using a multimodal academic detailing approach with group and individual educational sessions. Its effectiveness was tested using a modified step-wedge implementation design. The primary outcomes were patient behaviors that could plausibly be changed by conversations with their provider: the rate at which cancer patients identified as current tobacco users scheduled an appointment in the Nicotine Dependence Center, and the rate at which patients scheduled for a NDC appointment completed their appointment. Comparisons were made before, during, and after the education period (from July through Dec 2019) and with a separate group of providers who did not complete education (results examined over a similar time period). Results: Education intervention did not improve outcomes among providers who received education; indeed, the rate of appointment scheduling decreased, although this may reflect other concurrent changes in the tobacco treatment referral process (Table 1). Outcomes were similar between oncology providers who did and did not receive multicomponent education intervention. Conclusions: Smoking cessation efforts can be successfully integrated into routine cancer care. The implementation of the “opt-out” referral system resulted in approximately 1 in 5 patients being seen for tobacco use, but a multicomponent education intervention designed to equip oncologists to encourage patients to complete appointments was not effective. Novel approaches are needed to increase the uptake of tobacco treatment among patients.[Table: see text]

AbstractThis report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.