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Heart Failure Devices: Treatment Options, Underutilization, and a Proposed Trigger System for Patient Referral and Evaluation
No full textThe use of guideline-directed medical therapy (GDMT) has substantially prolonged and improved the lives of patients with heart failure (HF). Nevertheless, adherence rates remain suboptimal. Even when successfully maximized and adhered to, there is a substantial residual risk of recurrent HF hospitalization and death. In light of this, there is a strong need for effective interventions that can decrease the high residual risk seen in patients with HF. Several device options exist that are approved by the US Food and Drug Administration and that have been shown to decrease morbidity and/or mortality in patients among whom GDMT is maximized. These strategies include valvular interventions (aortic valve replacement, mitral valve repair, and tricuspid valve repair or replacement), cardiac resynchronization, cardiac contractility modulation, remote hemodynamic monitoring, and baroreceptor activation therapy. The pivotal trials for each of these interventions, and the patient populations for which they have been approved, are discussed. Current rates of device use in clinical practice remain very low. For many device classes, the vast majority of eligible patients are not offered or prescribed the device. Several reasons may explain this mismatch, foremost of which is a lack of clinical awareness about when to escalate therapy, how to identify patients requiring more than GDMT, and access to centers with sufficient experience. To aid the appropriate uptake of device therapy in clinical practice, we propose a simple mnemonic for use by clinicians that can prompt the early identification and prompt referral of patients with HF who likely merit consideration of additional device-based therapy in addition to GDMT
Impact of peripheral circadian misalignment and alcohol on the resiliency of intestinal barrier and microbiota
No full textCircadian organization is involved in many gastrointestinal tract (GIT) functions such as the maintenance of intestinal barrier integrity. There is compelling evidence that perturbation of the circadian clock decreases intestinal epithelial cells\u27 resiliency to alcohol-induced injury. One of the most common causes of circadian misalignment is wrong-time eating (largest meal at dinner) in modern societies. Yet, few studies have examined the importance of peripheral circadian rhythms of the GIT to alcohol consumption. Eating patterns during physiologic rest time, defined as wrong-time eating (WTE), misalign the peripheral circadian clock of the GIT and the body\u27s central clock. This study aims to fill this knowledge gap by testing the hypothesis that: (1) WTE worsens alcohol-induced disruption of intestinal barrier integrity and (2) decreased intestinal barrier resiliency to alcohol effects by WTE-disrupted circadian is, at least in part, due to microbiota dysbiosis. Alcohol (20% v/v) and a restricted timed-food paradigm were administered to PERIOD2 luciferase (PER2:LUC) reporter BL/6 mice for 10 weeks. Intestinal barrier integrity, intestinal (stool) microbiota, and microbial metabolites (cecal-derived) were examined. Peripheral circadian misalignment exacerbated alcohol-induced disruption of intestinal barrier integrity (tight junctional proteins) leading to increased intestinal permeability (p \u3c 0.05). In addition, alcohol consumption changed the intestinal microbiota community, decreasing beneficial short-chain fatty acid-producing taxa. Further, we recapitulated the in vivo phenotype in a colonic organoid model and demonstrated that microbial metabolites from circadian-disrupted, alcohol-fed mice mediate decreased resiliency of intestinal epithelial barrier function. Peripheral circadian misalignment through food timing decreases the resiliency of the intestinal barrier to alcohol-induced injury and this effect is mediated through dysbiotic microbiota metabolites
Building Boundary-Crossers in Clinical-Translational Research: An Exploratory Study of a Novel Communication Intervention
No full textINTRODUCTION: Integrating scientific research across multiple disciplines to advance breakthroughs is at the heart of clinical-translational science (CTS); among competencies that have been identified as essential for progress, skillful communication is critical. Few tools are available to address the social dynamics of the multidimensional diversity characteristics of CTS. We created the Building a Diverse Biomedical Workforce Through Communication Across Difference (CAD) workshop intervention. Based on principles of intercultural communication, CAD taught novel situationally-based communication skills to dyads of near-peer mentors and their undergraduate mentees. This study reports on the effectiveness of the operative mechanisms employed in CAD workshops for helping participants navigate highly diverse research environments.
METHODS: Participant data were collected from multiple sources, including workshop artifacts as well as focus groups conducted post-workshop. Data were organized, individually coded, and then iteratively and collectively into pre-defined and emergent themes.
RESULTS: Responses indicated that the content and activities resonated strongly with participants and illuminated their understanding of challenges (both their own and others\u27) related to belonging, confidence, and connectedness to the research environment; several participants shared that they planned to use or had successfully used the skills. Focus group comments revealed that participants recognized the potential of the skills to include significant opportunities for non-instrumental interaction, contributing to a psychologically healthier workplace.
CONCLUSION: A brief intervention to develop communication skills across a variety of differences characteristic of clinical-translational settings improves communication between mentors and mentees and with peers and increases sense of belonging in the workplace, with potential benefits to wellbeing
Empathy Unmasked: Patient Perception of Physician Empathy in an Oncologic Emergency Setting A Randomized Controlled Trial Comparing Personal Protective Equipment Wear versus Unmasked Video Communication
No full textBackground: Amidst the COVID-19 pandemic, telemedicine emerged as an important option that supports and facilitates clinical practice, however, its usefulness in emergency settings that treat patients with cancer is unclear.
Objective: To evaluate patient perception of physician empathy in an emergency oncology setting, comparing video interaction to an in-person with personal protective equipment (PPE) approach.
Methods: In this single-center, prospective, cross-sectional, survey-based randomized controlled trial, patients were randomized 1:1 for the concluding conversation done in-person which included either interacting with physicians wearing PPE or video interaction with physicians without PPE (virtual). Patients\u27 perceptions of the physicians\u27 relational empathy were assessed and compared for each group by using the Consultation and Relational Empathy (CARE) Measure and the Perception of Physician Compassion measure.
Results: Patients (n = 106) in both the PPE and virtual arms provided favorable responses to all questions. The mean overall CARE scores for the PPE and virtual arms were 45.02 and 44.43, respectively (difference, 0.58 [95% CI: -2.10, 3.30]). Regarding the linear physician compassion scores, patients in the virtual arm appeared to consider physicians to be warmer (difference, -0.42 [95% CI: -0.87, 0.04]) but less pleasant (difference, 0.33 [95% CI: -0.40, 1.10]) than did patients in the PPE arm.
Conclusions: Cancer patients presenting to the emergency department perceive empathy and compassion equally when approached by physicians virtually without PPE or in person while wearing PPE. Virtual services for specific aspects of clinical practice during emergency department visits in an oncology setting can be implemented to ensure safer interactions between patients and physicians without compromising the physician-patient relationship
Clinical Course and Treatment Outcomes in Solid-Basaloid Adenoid Cystic Carcinoma of the Breast: A Systematic Review and Case Report
No full textBackground: Adenoid Cystic Carcinoma (ACC) is a rare, indolent subtype of triple-negative breast cancer, accounting for \u3c 0.1 % of cases. The solid-basaloid subtype (SBACC), comprising approximately one-quarter of breast ACCs, has a poorer prognosis. While ACC is typically managed with surgery and is chemo-resistant, SBACC is more aggressive and often treated with chemotherapy and, more recently, immunotherapy-though supporting evidence remains limited.
Aim: To assess clinical characteristics and treatment outcomes of SBACC of the breast.
Methods: This study presents a case of breast SBACC and a systematic review of five databases (inception-September 10, 2024). Eligible studies reported clinical course, treatment, and outcomes. Exclusions included duplicates, non-SBACC focus, animal studies, and those lacking clinical or with only pathological data. Descriptive statistics were used for binary and categorical variables. Risk of bias was assessed using JBI tools, following PRISMA 2020 guidelines. The review is registered in PROSPERO.
Results: Nineteen studies and one new case (134 patients, aged 19-89) were included. Except for three patients who had with metastatic disease at diagnosis, the rest (97 %) were treated with surgery; 55.6 % received chemotherapy. Among nine patients given neoadjuvant chemotherapy and/or immunotherapy, none achieved complete pathological response, and most had poor outcomes. In non-metastatic cases with reported treatment (n = 99), younger age predicted recurrence (p = 0.032) but not chemotherapy receipt (p = 0.082). Chemotherapy did not reduce recurrence risk (p = 0.819). Mastectomy versus breast-conserving surgery with radiation had similar outcomes (p = 0.197).
Conclusions: Although limited data are available for this rare cancer, evidence for the efficacy of chemotherapy and immunotherapy for SBACC treatment is lacking. Treatment plans should be individualized to reduce the physical, psychological, and financial burdens on both patients and healthcare systems
Encorafenib, Cetuximab and Chemotherapy in Braf-Mutant Colorectal Cancer: A Randomized Phase 3 Trial
No full textEncorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC. The dual primary endpoint of progression-free survival is event driven; data were not mature at data cutoff. BREAKWATER met the other dual primary endpoint of objective response rate, demonstrating significant and clinically relevant improvement in objective response rate (EC+mFOLFOX6: 60.9%; SOC: 40.0%; odds ratio, 2.443; 95% confidence interval (CI): 1.403-4.253; 99.8% CI: 1.019-5.855; one-sided P = 0.0008). Median duration of response was 13.9 versus 11.1 months. At this first interim analysis of overall survival, the hazard ratio was 0.47 (95% CI: 0.318-0.691; repeated CI: 0.166-1.322). Serious adverse event rates were 37.7% versus 34.6%. The safety profiles were consistent with those known for each agent. BREAKWATER demonstrated a significantly improved response rate that was durable for first-line EC+mFOLFOX6 versus SOC in patients with BRAF V600E mCRC. ClinicalTrials.gov identifier: NCT04607421
ICOS and ICOS Ligand: Expression Patterns and Outcomes in Oncology Patients
No full textBackground: Inducible T-cell co-stimulator (ICOS) and its ligand (ICOSL) form a complex, two-faced immune machinery that can lead to both immune stimulation and inhibition.
Objective: We explored ICOS transcriptomic expression patterns and their relationship with other checkpoints and with outcomes in patients with advanced/metastatic cancers.
Design: This was a retrospective cohort study.
Methods: RNA expression for ICOS and other immune checkpoints was quantified by RNA sequencing and stratified by rank values into high (75-100 percentiles) and low (0-24 percentiles). Fischer\u27s exact tests were used for univariate analyses to evaluate independent predictors of ICOS high and logistic regression was used for multivariate analyses. Progression-free survival (PFS) and overall survival (OS) for ICOS high versus not high expression were evaluated using the log-rank test (Kaplan-Meier analysis) and Cox proportional hazards.
Results: High ICOS (⩾75 percentile RNA rank) was present in 14% of 514 cancers and independently associated with high PD-1 (p = 0.025), PD-L1 (p \u3c 0.0001), and CTLA-4 RNA expression (p \u3c 0.0001) and with patients not having colorectal cancer (p = 0.0009; multivariate analysis). Patterns of ICOS and ICOSL expression varied between and within tumor types. For 217 patients receiving immune checkpoint inhibitors (ICIs), there were no significant differences in PFS or OS between patients with ICOS high versus not-high expression (multivariate analysis). In 272 immunotherapy-naïve patients, OS was also similar between patients with ICOS high versus not-high expression (p = 0.91).
Conclusion: High ICOS expression was not a prognostic marker and did not independently predict outcomes after ICIs. Variable expression of ICOS/ICOSL between tumors and association of high ICOS with high PD-1, PD-L1, and CTLA-4 suggest that individual tumor immunomic analysis may be required for optimized patient selection in clinical trials targeting the ICOS/ICOSL system, especially when given in combination with ICIs
American Association of Physicists in Medicine (Aapm) Chapter Climate Check: Mixed Methods Analysis of Survey Responses
No full textIntroduction: The American Association of Physicists in Medicine (AAPM) recently shared results and recommendations from its first Equity, Diversity, and Inclusion (EDI) Climate Survey, which was designed to assess the climate at the workplace, the AAPM organization, and the AAPM regional chapter level. This work further explores the status of EDI at the regional chapter level.
Methods: AAPM\u27s EDI Survey was distributed to 5500 members and had a response rate of 25%. In the survey, three open-ended comment boxes were provided for feedback, including one for regional AAPM members. Sixty-four percent of respondents indicated they were part of a regional chapter, and 6% provided written responses to the regional chapter question. Responses were analyzed using a mixed methods approach with an exploratory sequential design. Two phases were conducted; the first relied on a Grounded Theory quantitative systemic approach, and the second applied qualitative analysis. Chapter member demographic data were collected to support findings.
Results: Survey respondents provided open comments and feedback on their regional chapter\u27s climate. Data are summarized as five themes: positive experiences, negative experiences, challenges within chapters, diversity and inclusion, and changes observed. Experiences of regional chapters were rated positively by 75% of respondents. Respondents found their chapters were welcoming, and some noted their great chapter leadership. A number of incidents of sexual harassment, bullying, and discrimination incidences were also shared. Other respondents observed exclusion based on their gender, race, highest degree, and medical physics specialty. Chapter leadership data aligned with these claims, with most leaders to-date being white males, doctoral degree holders, and/or specializing in radiation therapy.
Conclusion: AAPM chapters provide rewarding professional opportunities. This study has highlighted positive and negative experiences reported by its members. The major themes identified can guide chapter leaders to continue to cultivate welcoming communities for regional AAPM members
Tips on the PRISMA Flow Diagram & Methods Section Write-Up
No full textClearly communicate your research methodology with a well-crafted PRISMA flow diagram. This 30-minute class provides practical tips and a step-by-step guide to creating a clear and informative methods section for your research papers
Pediatric Myeloid Neoplasms With UBTF Tandem Duplications: Morphologic, Immunophenotypic, and Clinical Characterization
No full textTandem duplications (TDs) in exons of upstream binding transcription factor (UBTF-TD) are a rare recurrent alteration in pediatric and adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)/neoplasm. Although recently identified, AML with UBTF-TD is now considered a distinct subtype of AML. To further our understanding of myeloid neoplasms with UBTF-TD, we analyzed clinical, morphologic, and immunophenotypic characteristics of 27 pediatric patients with UBTF-TD-positive myeloid neoplasm, including 21 diagnosed as AML and 6 as MDS. Our data demonstrated that UBTF-TD is frequently associated with cytopenia, hypercellular marrow with erythroid hyperplasia, and trilineage dysplasia. Blasts and maturing myeloid cells show a characteristic dysplastic feature with condensed eosinophilic cytoplasm. Blasts have a myeloid or myelomonocytic immunophenotype with a variably dim expression of CD34 and/or CD117, and except for CD7 expression lack a consistent pattern of aberrant lineage-specific antigen expression. Patients with MDS had a lower blast count in the peripheral blood (P = 0.03) and bone marrow (P \u3c 0.001) but otherwise had no significant differences in other hematological parameters. Three patients with MDS rapidly progressed to AML in 33, 39, and 210 days from the initial diagnosis and there was no difference in overall survival between patients with MDS and AML (P = 0.18). Our data suggest that MDS with UBTF-TD is prognostically equivalent to AML with UBTF-TD and thus should be considered as a continuum of the same molecularly defined myeloid neoplasm. These collective data also provide morphologic and immunophenotypic clues that can prompt screening for UBTF-TD in patients with MDS or AML