tbuckley/cabot-search huggingface dataset:
Internalized β2-Adrenergic Receptors Oppose PLC-Dependent Hypertrophic Signaling
Authors: Wenhui Wei, Alan V. Smrcka
Journal: Circulation Research (2024)

Chronically elevated neurohumoral drive, and particularly elevated adrenergic tone leading to β-adrenergic receptor (β-AR) overstimulation in cardiac myocytes, is a key mechanism involved in the progression of heart failure. β1-AR (β1-adrenergic receptor) and β2-ARs (β2-adrenergic receptor) are the 2 major subtypes of β-ARs present in the human heart; however, they elicit different or even opposite effects on cardiac function and hypertrophy. For example, chronic activation of β1-ARs drives detrimental cardiac remodeling while β2-AR signaling is protective. The underlying molecular mechanisms for cardiac protection through β2-ARs remain unclear.
Blood eosinophils and lung function loss: from passive prediction to active prevention?
Authors: Sanjay Ramakrishnan, Brett Montgomery, Ian D. Pavord
Journal: European Respiratory Journal (2024)

<h3>Shareable abstract</h3> <b>Combining raised blood eosinophil counts and exacerbations could help us identify patients without lung disease who are at highest risk of rapid progressive lung function decline</b>https://bit.ly/3yiDtZf
Fostering Psychological Safety and Supporting Mental Health Among Cardiovascular Health Care Workers: A Science Advisory From the American Heart Association
Authors: Laxmi S. Mehta, Keith Churchwell, Dawn Coleman, Judy Davidson, Karen Furie, Nkechinyere N. Ijioma, Jason N. Katz, Christine Moutier, Jessica Y. Rove, Richard Summers, Alyssa Vela, Tait Shanafelt
Journal: Circulation (2024)

The psychological safety of health care workers is an important but often overlooked aspect of the rising rates of burnout and workforce shortages. In addition, mental health conditions are prevalent among health care workers, but the associated stigma is a significant barrier to accessing adequate care. More efforts are therefore needed to foster health care work environments that are safe and supportive of self-care. The purpose of this brief document is to promote a culture of psychological safety in health care organizations. We review ways in which organizations can create a psychologically safe workplace, the benefits of a psychologically safe workplace, and strategies to promote mental health and reduce suicide risk.
Comprehensive multi‐omics analysis provides biological insights and therapeutic strategies for small‐cell lung cancer
Authors: Guo Zhao, Yuning Wang, Shuhang Wang, Ning Li
Journal: MedComm (2024)

Integration of multi-omics analysis into small-cell lung cancer (SCLC) research. In the research of small-cell lung cancer, the integration of multi-omics analysis has become an important research direction. Multi-omics analysis includes the study of genomics, transcriptomics, proteomics, metabolomics, and other levels, which can help us to understand the pathogenesis and development process of diseases more comprehensively as well as develop novel therapeutics and biomarkers for further precision oncology.
Long versus short course anti-microbial therapy of uncomplicated Staphylococcus aureus bacteraemia: a systematic review
Authors: Martin Schnizer, Paul Schellong, Norman Rose, Carolin Fleischmann-Struzek, Stefan Hagel, Mohamed Abbas, Brendan Payne, Rebecca N. Evans, Mathias W. Pletz, Sebastian Weis
Journal: Clinical Microbiology and Infection (2024)

BackgroundCurrent guidelines recommend at least two weeks duration of antibiotic therapy (DOT) for patients with uncomplicated Staphylococcus aureus bacteraemia (SAB) but the evidence for this recommendation is unclear.ObjectivesTo perform a systematic literature review assessing current evidence for recommended DOT for patients with SAB.MethodsData sources: We searched MEDLINE, ISI Web of Science, the Cochrane Database and clinicaltrials.gov from inception to March 30, 2024. References of eligible studies were screened and experts in the field contacted for additional articles.Study eligibility criteriaAll clinical studies, regardless of design, publication status and language.ParticipantsAdult patients with uncomplicated SAB.InterventionsLong (>14; >18; 11-16 days) vs. short (≤14; 10-18; 6-10 days, respectively) DOT with the DOT being defined as the first until the last day of antibiotic therapy.Assessment of risk of biasRisk of bias was assessed using the ROBINS-I-tool.Methods of data synthesis: The primary outcome was 90-day all-cause mortality. Only studies presenting results of adjusted analyses for mortality were included. Data synthesis could not be performed.ResultsEleven non-randomized studies were identified that fulfilled the predefined inclusion criteria, of which three studies reported adjusted effect ratios. Only these were included in the final analysis. We did not find any RCT. Two studies with 1,230 patients reported the primary endpoint 90-day all-cause mortality. Neither found a statistically significant superiority for longer (>14; 11-16 days) or shorter DOT (≤14; 6-10 days, respectively) for patients with uncomplicated SAB. Two studies investigated the secondary endpoint 30-day all-cause mortality (>18; 11-16 days vs. 10-18; 6-10 days, respectively) and did not find a statistically significant difference. All included studies had a moderate risk of bias.ConclusionsSound evidence that supports any duration of antibiotic treatment for patients with uncomplicated SAB is lacking.
Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study
Authors: Mingchao Xie, Miljenka Vuko, Jaime Rodriguez-Canales, Johannes Zimmermann, Markus Schick, Cathy O’Brien, Luis Paz-Ares, Jonathan W. Goldman, Marina Chiara Garassino, Carl M. Gay, John V. Heymach, Haiyi Jiang, J. Carl Barrett, Ross A. Stewart, Zhongwu Lai, Lauren A. Byers, Charles M. Rudin, Yashaswi Shrestha
Journal: Molecular Cancer (2024)

Abstract Background We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial. Methods 805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall survival (OS). Patients were required to provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening, if these samples existed. After assessment for programmed cell death ligand-1 expression and tissue tumor mutational burden, residual tissue was used for additional molecular profiling including by RNA sequencing and immunohistochemistry. Results In 182 patients with transcriptional molecular subtyping, OS with D ± T + EP was numerically highest in the SCLC-inflamed subtype ( n = 10, median 24.0 months). Patients derived benefit from immunotherapy across subtypes; thus, additional biomarkers were investigated. OS benefit with D ± T + EP versus EP was greater with high versus low CD8A expression/CD8 cell density by immunohistochemistry, but with no additional benefit with D + T + EP versus D + EP. OS benefit with D + T + EP versus D + EP was associated with high expression of CD4 (median 25.9 vs. 11.4 months) and antigen-presenting and processing machinery (25.9 vs. 14.6 months) and MHC I and II (23.6 vs. 17.3 months) gene signatures, and with higher MHC I expression by immunohistochemistry. Conclusions These findings demonstrate the tumor microenvironment is important in mediating better outcomes with D ± T + EP in ES-SCLC, with canonical immune markers associated with hypothesized immunotherapy mechanisms of action defining patient subsets that respond to D ± T. Trial registration ClinicalTrials.gov, NCT03043872.
Impact of a care delivery intervention for patients with socioeconomic disadvantages, in their preferred language of English or Spanish.
Authors: Sarah Khan, Christine B. Weldon, Julia R. Trosman, Tierra Valentine, Jorge Hernandez, SWETHA PADURI, Vijay Ketan Reddy, Anuradha Sakhuja, Daniel Czarnowski, Twinkle Patel, Margarita Oliveras, Sandra Ramirez, Emilia Williams, Gautam Valecha, Mohammed Azher Kassem, Jaya Sharma, Seshan Subramanian, Arliene Ravelo, Paramjeet Grewal Khosla
Journal: Journal of Clinical Oncology (2024)

e13550 Background: Sinai Health System’s oncology program serves Chicago’s inner city patients with substantial needs for social and primary care, many of whom prefer communication in Spanish. Sinai has implemented a care delivery intervention to address these needs, using the 4R Oncology Model for patient-facing care planning and patient self-management. 4R (Right Info/Care/Patient/Time) has shown significant improvements in the timeliness of care cancer delivery and referrals to cancer care (1). Herein, we implemented the 4R intervention to improve the timeliness of care delivery and referrals to care, focusing on the social and primary care needs of Sinai patients. Methods: Evaluation was conducted by surveying historical control and intervention (4R) cohorts of patients in their preferred language of Spanish or English. The 4R cohort received care at a Sinai medical oncology clinic Apr 2023 - Jan 2024. Control cohort received care Jan 2023 – March 2023. Analyses were conducted using Fisher’s exact test. Results: Survey response: 76% (38/50) in control and 75% (33/44) in 4R cohorts. Participant characteristics were comparable between control and 4R cohorts, respectively: 55%, 58% Hispanic, 42%, 39% Black; 76%, 82% high school education or less; 87%, 97% &lt; $30k annual income; 50%, 55% preferred Spanish; 47%, 45% preferred English. For the total cohorts, all 5 metrics improved between control and 4R, and 4 of the 5 metrics improved significantly (Table). Among Spanish-preferred patients, 3 of the 5 metrics improved significantly, while improvements among English-preferred patients were not statistically significant. Both language groups saw numerical, but not statistically significant improvement in receiving referrals to primary care and meeting all their practical and family needs. Conclusions: The 4R Oncology intervention resulted in significant improvement in time to treatment and referrals to social and primary care in our population of socioeconomically disadvantaged patients with high needs for these services. Patients preferring Spanish benefited at a higher rate than English-preferring patients, indicating that 4R may be an effective method to address the needs of this important patient group. Future efforts will further optimize 4R to address remaining gaps for this group, as well as to improve the delivery of this care for the English-preferred patients. 1. Trosman JCOOP 2021. [Table: see text]
Ethnic disparities in breast cancer: A comprehensive analysis of socio-demographic and clinical characteristics among African American, Hispanic, and Caucasian women.
Authors: Ekaterina Proskuriakova, Barun Babu Aryal, Dhan Shrestha, Megan Adams, Stephanie Valencia, Akshay Varsani, Anuradha Sakhuja, Ranjit Babu Jasaraj, Iuliia Kovalenko, Larissa Verda, Paramjeet Grewal Khosla
Journal: Journal of Clinical Oncology (2024)

e13698 Background: Despite advancements in breast cancer therapy leading to a decline in mortality rates within certain ethnic populations, there exists a concerning trend of increasing cancer incidence among African American (AA) and Hispanic women. This persistent rise highlights the urgent need to explore and comprehend the socio-demographic and breast cancer characteristics specific to these populations. Methods: We assembled a 10-year database of women diagnosed with breast cancer in the community hospital in Chicago. After excluding minority ethnic groups, specifically AA, Hispanic, and Caucasian cohorts were included in this study, comprising 786 patient records analyzed. Results: The distribution revealed a predominance of AA patients at 49.7%, Hispanics at 42.1%, and Caucasians at 8.14%. Noteworthy differences across the three ethnic groups were observed in age categories at cancer diagnosis, BMI categories, family history of first-degree relatives with breast cancer, marital status, smoking habits, menopausal status, and alcohol use at the time of diagnosis (p &lt; 0.05). Within the molecular subtypes, 14.5% were identified as triple-negative breast cancer (TNBC), with a higher prevalence of 18.7% among the AA subgroups. 19.6% of patients had advanced disease, proportion was higher in AA ethnic group (22.8%; p = 0.83) compared to other ethnicities. Breast conservative procedures were prevalent in almost half of the patient population on average (52.1 %), with a slightly higher frequency of mastectomies noted in the Hispanic patient group (44.1%, p &lt; 0.05). In logistic regression analysis, compared to the reference AA ethnicity, Hispanics exhibited higher odds of having HER-2 positive breast cancer (OR 1.74; CI 1.04 – 2.94; p &lt; 0.05), as did Caucasians (OR 2.35; CI 1.05 – 5.04; p &lt; 0.05). Conclusions: In summary, our study underscores substantial socio-demographic and breast cancer characteristic differences among AA and Hispanic populations compared to Caucasians, revealing notable ethnic disparities in breast cancer. Despite these variations, our findings highlight promising healthcare equity, with comparable access to surgical and chemotherapy interventions across ethnicities. TNBC demonstrates molecular heterogeneity and a higher prevalence among AA women, contributing to significant racial disparities.
Effect of age on delivering chemotherapy to older adults with advanced pancreatic adenocarcinoma.
Authors: Toufic Tannous, Ekta Panjrolia, Natasha M. Resendes, Raiyan Islam, Iriana M. Hammel
Journal: Journal of Clinical Oncology (2024)

e13767 Background: Age is one of the most important risk factors for developing pancreatic adenocarcinoma (PDAC), 65% of the newly diagnosed cancer cases occur in individuals above 65 years of age (yo). The only potential cure for PDAC includes surgical resection, however, the majority of patients (70%) present with locally advanced/unresectable or metastatic PDAC (APDAC). Many oncologists remain hesitant to administer treatment to older adults for fear of perceived increased chemotoxicity risk and the thought of treatment intolerability. Methods: This retrospective cohort study included patients who were diagnosed and treated for APDAC within the Veterans Integrated Services Network (VISN) 8 which includes Veterans Affairs medical facilities in Florida, southern Georgia, Puerto Rico, and the U.S. Virgin Islands. Demographic data such as age, sex, race, ethnicity and treatment data such as chemotherapy and palliative care use were pulled from the VA Cancer Registry, available from Corporate Data Warehouse Data. We conducted a detailed chart review in the VA electronic health record to confirm stage and the eastern cooperative oncology group (ECOG) status at the time of diagnosis. Statistical analyses were conducted using GraphPad Prism 10.1.2 software. Analyses consisted of t-test for normally distributed continuous variables, chi-squared test for categorical variables and the Mann Whitney U test for the ECOG score of both groups. Results: Ninety-nine patients with APDAC above the of age 65 were identified from the period of June 1, 2017 till July 31, 2021. 46 received chemotherapy (C group) and 53 patients did not receive chemotherapy (NC group), characteristics (Table). The mean age for those in the C group were 72 years old (yo) vs 76 yo from the NC group with a P value of 0.0017 which was statistically significant. Looking at the age subgroups, the majority of the patients that received C, were of the 65-74 age subgroup (71%). The median ECOG for the NC group was 2 and that for C was 1 group. 39% of the C group received palliative care as opposed to 32% of the NC group with a P value of 0.532. Conclusions: Despite an acceptable ECOG range between 1 and 2, Age played an important factor in determining who received chemotherapy in APDAC. Studies other than ECOG are needed to help oncologists determine the fitness of APDAC patients and minimize hesitancy to deliver treatment. The involvement of palliative care in patients with APDAC was suboptimal and a push for more involvement of palliative care is needed. [Table: see text]
A nationwide analysis of demographic and treatment patterns in admissions for malignant pleural effusions from 2016-2020.
Authors: Lina James George, Ekrem Turk, Youjin Oh, Alejandro Vallejo, Angelo Caputi, Shweta Gupta
Journal: Journal of Clinical Oncology (2024)

1618 Background: Malignant pleural effusions are an indicator of metastatic malignancy, with poor survival and need for palliative procedures to alleviate symptoms. Our study aims to identify the disparities in the utilization of these procedures and their effects on hospitalization outcomes. Methods: The Nationwide Inpatient Sample (NIS) was used to identify all adult hospitalizations with malignant pleural effusion (MPL) between the years 2016-2020. We studied patient demographics and treatment modalities during admission. The study's primary outcome measure was to identify the difference in the total length of stay (LOS) and total healthcare cost (THC)incurred during admission. The secondary outcome was mortality rates among patients undergoing these procedures. Statistical analysis was done using multivariate linear and logistic regression models. Results: A total of 439,245 admissions for MPL were identified, constituting 0.2% of all U.S. admissions. Among these, 59.6% were females and mean age was 67.3 years. There were 68% Whites, 15% Blacks, 8% Hispanics, 4% Asians or Pacific Islanders, 0.4% Native Americans, and 2.9% others. About 61% had Medicare, 11.2% Medicaid, 25.7% Private insurance, and 1.9% Self-pay. Most admissions occurred in teaching hospitals (76.3%), urban settings (94.5%), and hospitals with larger bed strength (56.1%). The most common primary admission diagnosis was sepsis (8.3%). The most common primary malignancies were Lung (39.9%), breast (27.9%), gastrointestinal (9%), and hematopoietic malignancies (7.1%). We studied rates of thoracocentesis, Pleurodesis, Decortication, and intrapleural chemotherapy. The mean LOS and THC increased in admissions where procedures were performed, highest for decortication (12.1 days, p&lt;0.01). However, the odds of death in hospitals significantly reduced. When compared to primary lung cancer causing malignant effusions, primary G.I., renal, urinary, and upper aerodigestive malignancies with MPL had significantly higher mortality rates (p&lt;0.05). Disparities were observed in procedures performed, with women having 29% lower odds of undergoing decortication (p&lt;0.001). African Americans had lower odds of undergoing any procedures for MPL when adjusted for age, sex insurance status, compared to whites. Teaching hospitals had 10.9 times higher odds of performing thoracocentesis but lower odds of performing pleurodesis and decortication (p&lt;0.05). Conclusions: This investigation provides insights into the favorable impact of invasive procedures on in-hospital mortality for malignant pleural effusions, suggesting a possibility that patients with better performance status underwent such interventions. We also noted racial and sex-based disparities in the performance of these procedures. Further studies are essential to identify the reasons for this disparity to help promote equitable care.
Generative AI enhanced with NCCN clinical practice guidelines for clinical decision support: A case study on bone cancer.
Authors: Yanshan Wang, Xizhi Wu, Luke Carlson, David Oniani
Journal: Journal of Clinical Oncology (2024)

e13623 Background: Bone cancer is a complex and challenging disease to diagnose and treat in clinical practice. Recently, generative AI, especially large language models (LLMs), has demonstrated potential as a decision support tool for cancer. However, most implementations have overlooked the integration of available cancer guidelines, such as the NCCN Bone Cancer Guidelines, in fine-tuning the outputs of generative AI models. Incorporating these guidelines into LLMs presents an opportunity to harness the extensive clinical knowledge they contain and improve the decision-support capabilities of the model. Methods: In this study, the aim is to enhance the LLM with cancer clinical guidelines to enable accurate medical decisions and personalized treatment recommendations. Therefore, we introduce a novel method for incorporating the NCCN Bone Cancer Guidelines into LLMs using a Binary Decision Tree (BDT) approach. The approach involves constructing a BDT based on NCCN Bone Cancer Guidelines, where internal nodes represent decision points from the Guidelines, and leaf node signify final treatment suggestions. Then the LLM makes decision at each internal node, considering a given patient's characteristics, and guides toward a treatment recommendation in the leaf node. To assess the efficacy of Guideline-enhanced LLMs, an oncologist from our team created 11 hypothetical osteosarcoma patients’ medical progress notes. Each note contains their demographics, medical history, current illness, physical exams, diagnostic tests. We tested three LLMs in the implementation (GPT-4, GPT-3.5, and PaLM 2) and compared the LLM-generated treatment recommendations with the gold standard treatment across four runs with different random seeds (random seeds is a setting to control the LLM outputs). The results are reported as the average of four runs. The original LLMs are used as baseline methods for comparison. Results: The table below provides a comparison between the performance of original LLMs and those augmented with cancer guidelines for osteosarcoma treatment recommendations. We can observe that the PaLM 2 model demonstrated superior performance compared to its counterparts, underscoring the effectiveness of integrating cancer guidelines into LLMs for decision support. Conclusions: The clinical decision support capabilities of the LLMs are promising when enhanced by NCCN Bone Cancer Guidelines using our approach. To fully exhibit the potential of our proposed method as a clinical decision support tool, further investigation into other subtypes of bone cancer should be conducted in the future study. [Table: see text]