bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors influencing the mortality risk of heart failure in patients receiving antineoplastic immunotherapy: A national inpatient database study 2016-2020.
Authors: Shah Purva , Orakzai Abdullah Ahmad , Kharel Himal , Sanjeevi Aditya , Eltaher Basant , Easow Jose M. 
Published: June 2024

e24011 Background: Immunotherapy is increasingly being used for management of solid and lymphoproliferative tumors due to their more desirable side effect profile as compared to traditional cancer therapies. However, these medications are associated with cardiac complications and little is known about the factors influencing the prognosis in these patients. Methods: This is a retrospective analysis of the National Inpatient Database from 2016 to 2020 using the International Classification of Diseases (ICD) 10 codes performed with STATA BE 18.0. Chi square test was used for crude analysis and multivariate logistic regression was performed to assess the risk of inpatient death among cancer patients with heart failure receiving immunotherapy. Results were adjusted for potential confounders like age, gender, race, hypertension, diabetes, coronary artery disease, smoking, and alcohol consumption. Multicollinearity of the model was assessed using Variance Inflation Factor (VIF) post-estimation test. Results: Out of 5166 cancer patients receiving immunotherapy with a mean age of 43.63 土 26.33 years and 41% females, 45 patients had heart failure. Logistic regression showed that heart failure was significantly associated with mortality (LR 𝜒² 38.74, p value < 0.001) on adjusting for potential confounders. Although the effect size was small, increased age (OR 1.025, CI 1.01-1.04) had a significantly higher risk of mortality. Patients belonging to the female gender and white, hispanic, and asian races had a lower risk of mortality while those belonging to the african american race and those with coronary artery disease had a higher mortality risk, although not statistically significant. Diabetes and alcohol consumption had a fourfold and sixfold increased risk of mortality respectively. Hypertension and smoking that are known to increase mortality risk in heart failure patients showed a paradoxically protective effect in this cohort. Conclusions: This study highlights the importance of risk stratification and prognostication among patients with heart failure receiving antineoplastic immunotherapy. Increased age, african american race, diabetes, alcohol consumption, and coronary artery disease have shown an increased mortality risk in these patients. [Table: see text]
Effect of sodium-glucose cotransporter 2 inhibitor dapagliflozin on systemic H-FABP and monocyte-to-lymphocyte ratio in preclinical models of antracycline induced cardiotoxicity.
Authors: Maurea Nicola , Canale Maria Laura , Bisceglia Irma , De Laurentiis Michelino , Bruzzese Francesca , Palma Giuseppe , Luciano Antonio , Iovine Martina , Paccone Andrea , Giacobbe Ilaria , Giordano Vienna , Izzo Francesca , Barbato Matteo , Arianna Raffaele , Inno Alessandro , Quagliariello Vincenzo 
Published: June 2024

e24012 Background: Anthracyclines are an effective and widely used chemotherapy agent in the treatment of multiple solid organ tumors and hematologic malignancies. The use of anthracyclines as a standard cancer therapy is limited by the potential for the development of cardiac dysfunction, arrhythmias, and clinical heart failure. Dapagliflozin exerts several cardiometabolic benefits in patients with and wthout T2DM through SGLT2-NLRP3 mediated pathways. In this study, we highlighted on new beneficial properties of Dapagliflozin in preclinical models of doxorubicin-induced cardiotoxicity. Methods: Female C57Bl/6 mice were untreated (Sham, n = 6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n = 6), DAPA at 12 mg/kg (DAPA, n = 6) or doxorubicin combined to DAPA (DOXO–DAPA, n = 6). After treatments, plasma levels of H-FABP and monocyte-to-lymphocyte ratio were determined through selective quantitative methods. Results: Dapagliflozin associated to Doxorubicin reduces of 48,7% plasma levels of H-FABP compared to DOXO group (p < 0.001). Myocardial expression of H-FABP were also reduced, indicating cardioprotective properties of SGLT2i. Moreover, monocyte-to-lymphocyte ratio was strongly enhanced after DOXO therapy, indicating systemic pro-inflammatory properties; notably, Dapagliflozin reduced of 32,8% the monocyte-to-lymphocyte ratio compared to only DOXO treated mice (p < 0.005). Conclusions: For the first time, Dapagliflozin demonstrated a significant reductions of monocyte-to-lymphocyte ratio during doxorubicin therapy, indicating new potential pathways of cardioprotection in cancer patients
Effect of sodium-glucose cotransporter 2 inhibitor dapagliflozin on ejection fraction reduction, myocardial and renal NF-κB expression and systemic pro-inflammatory biomarkers in models of short-term doxorubicin cardiotoxicity.
Authors: Quagliariello Vincenzo , Canale Maria Laura , Bisceglia Irma , Inno Alessandro , Bruzzese Francesca , Palma Giuseppe , Luciano Antonio , Iovine Martina , Giacobbe Ilaria , Maurea Fabrizio , Giordano Vienna , Izzo Francesca , Barbato Matteo , Arianna Raffaele , Berretta Massimiliano , Maurea Nicola 
Published: June 2024

e24013 Background: Anthracycline-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in cancer patients. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exerts multiple cardiometabolic benefits in patients with/without type 2 diabetes, chronic kidney disease and heart failure with reduced and preserved ejection fraction. We hypothesized that the SGLT2i Dapagliflozin administered before and during doxorubicin therapy, could improve cardiac function and reduce pro-inflammatory pathways in preclinical models. Methods: Female C57Bl/6 mice were treated for 10 days with a saline solution or DOXO (2.17 mg/kg), DAPA (10 mg/kg) or DOXO combined to DAPA. Systemic levels of ferroptosis-related biomarkers, galectin-3, hs-CRP and pro-inflammatory chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified. After treatments, immunohistochemical staining of myocardial and renal p65/NF-kB was performed. Results: DAPA prevented the reduction of radial and longitudinal strain and ejection fraction after 10 days of treatment with DOXO. A reduced myocardial expression of NLRP-3 and MyD-88 was seen in DOXO-DAPA group compared to DOXO mice. Systemic levels of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with DAPA. Serum levels of galectine-3 and hs-CRP were strongly enhanced in DOXO group; contrary, their expression were reduced in DAPA-DOXO group. Troponin-T, BNP and NT-pro-BNP were strongly reduced in DOXO-DAPA group, revealing cardioprotective properties of SGLT2-i. Mice treated with DOXO and DAPA exhibited reduced myocardial and renal NF-kB expression. Conclusions: The overall picture of the study encourages the use of DAPA in primary prevention of cardiomyopathies induced by anthracyclines in cancer patients.
Impact of cardiac arrhythmias on in-hospital mortality in patients with cytokine release syndrome: Insights from National Inpatient Sample.
Authors: Karam Wissam , Akkawi Abdul Rahman , Zakhour Joud , Alqam Anas , Shah Raj N. , Nabbout Nassim H. 
Published: June 2024

e24017 Background: Cytokine release syndrome (CSR) is a pervasive inflammatory response characterized by elevated body temperature and multi-organ dysfunction. This syndrome is linked to chimeric antigen receptor (CAR)-T cell therapy, various immunotherapies, or haploidentical hematopoietic cell transplantation (HCT). It can manifest as a fever, fatigue, headache, rash, diarrhea, arthralgia, and myalgia. In some cases, it can progress to hypotension, hypoxia, and an uncontrolled systemic inflammatory response leading to circulatory collapse, pulmonary edema, renal damage, and multi-organ failure. Cardiac evaluation in the context of CSR is crucial for assessing these manifestations, but little is known about the arrhythmias associated with this therapy, and there is limited information in the literature. Methods: A retrospective study using the National Inpatient Sample to identify patients diagnosed with CRS, and the arrhythmias they experienced during their hospitalizations between January and December 2020. The primary endpoint was the incidence of various arrhythmias. Furthermore, Independent predictors of in-hospital mortality were analyzed, with p values, adjusted odds ratios (aOR) and confidence intervals (CI) calculated for each variable. Results: A total of 4675 patients were diagnosed with CRS in 2020, 39% of whom were females. The mortality rate of patients with CRS was 22%. In addition, the mortality rate of patients who developed arrhythmias was 43% while that of patients who did not was 17% (p < 0.01). The mean age was higher in the arrhythmia cohort compared with the non-arrhythmia cohort (70 vs 60.7 years, p < 0.01). Predictive factors associated with increased mortality included development of arrhythmias, age, hispanic race, asian or pacific islander race, obesity, previous myocardial infarction, and electrolyte abnormalities with an aOR of 2.22 (P < 0.01, CI 1.51-3.28), 1.03 (P < 0.01, CI 1.01-1.05), 1.85 (P = 0.04, CI 1.02-3.34), 2.57 (P = 0.014, CI 1.02-3.34), 1.72 (P = 0.018, CI 1.09-2.69), 3.26 (P = 0.008, CI 1.36-7.8), and 4.19 (P < 0.01, CI 2.7-6.4) respectively. Female sex was found to be protective against mortality with an aOR of 0.5 (P = 0.004, CI 0.31-0.8). Conclusions: Our study reveals that developing arrhythmias is more common in older patients with CRS. Patients diagnosed with arrhythmias during their hospitalization experienced poorer outcomes. Adjusted predictors of mortality include the development of arrhythmias during hospitalization, age, hispanic race, asian or pacific islander race, obesity, previous myocardial infarction, and electrolyte imbalances. Additionally, female sex was found to be a protective against mortality. Given these findings, physicians should strive to be more vigilant when treating patients with CRS who have any of these predictors of mortality until further data is available.
Cardio-Oncology Awareness: A multidisciplinary survey amongst health care trainees and practicing professionals at academic institutions.
Authors: Bansal Shruti , Misra Shagun , Khanna Rupali , Lal Punita , Sarangi Satya Sadhan , Kapoor Aditya , Kumar Shaleen 
Published: June 2024

e24023 Background: The awareness of cancer therapy-related adverse cardiac effects is incited by recent literature on cardiotoxicity incidence and detection strategies. Despite availability of guidelines, cardiotoxicity monitoring and treatment are not structurally performed across institutions. Aim: Assessing knowledge of health care professionals’ cardiac complications of cancer treatments, current perspectives on cardio-oncology ultimately to determine an agenda for improvements in practice. Methods: A web-based survey (Google Forms) was adapted from that of Ottawa Hospital Research Institute’s survey, consisting of 45 questions organized into 7 sections, modified according to our local needs and circulated to cardiologists, oncologists (radiation, medical) practicing or training in a multi-disciplinary setup and academic centers. Fortnightly reminders were sent for to receive a maximum response. The survey enquired about implementing respondent’s perception of cardio-oncology, availability of cardio-oncology services at the respondent’s institution, opinions towards current practice. A descriptive statistical analysis was carried out. Results: Fifty-five professionals completed the survey, of which 12 were cardiologists, 31 radiation oncologists, and 12 medical oncologists. Majority, 31 (54.5%) were trainees and only 1.8% had some formal training in cardio-oncology while 20% respondents reported to have a formal cardio-oncology training programme. Nearly 90% understood cardio-oncology as a stream to be able to identify side-effects and refer for treatment to the cardiologists while 84% felt that timely referral would improve outcomes.72% recognized follow-up and 67.3% felt patient education to be important component. Awareness of cardio-oncology guidelines was reported by 38.2% respondents. In the setting of metastatic cancer, there was a difference in risk tolerance for cardiotoxicity with the majority accepting 1-5% risk in curative setting and 56% accepting > 5% risk of cardiotoxicity in the metastatic setting. None of the institutions reported on having a formal training programme. Limited infrastructure (54.5%) and limited interest (47.3%) were cited the most common reasons. Conclusions: This survey identified that professionals recognize cardio-oncology services to be an important component of cancer treatment. Lack of formal training and awareness about guidelines was reported. There is a felt need for collaboration between cardiologists and oncologists to improve cardiovascular outcomes of cancer patients.
Predictors of long-term survival in immune checkpoint inhibitor (ICI)-associated myocarditis.
Authors: Wu Chia-Yun , Dubey Nikhil , Zubiri Leyre , Rouhani Sherin Juliet , Sun Joie , Neilan Tomas G. , Reynolds Kerry Lynn , Zlotoff Daniel A. 
Published: June 2024

e24026 Background: ICI-associated myocarditis carries a high morbidity and mortality, with close to half of patients experiencing major adverse cardiac events (MACE). Risk factors previously associated with short-term MACE include troponin T (TnT), neutrophil/lymphocyte ratio (NLR), and absolute lymphocyte count (ALC). In this study, we aimed to analyze the predictors of long-term survival. Methods: This single-center retrospective study included 37 patients diagnosed with ICI-associated myocarditis at Massachusetts General Hospital between March 2016 and March 2022. We collected demographics, diagnostic results, and myocarditis treatments from the electronic medical record. Patients were grouped by survival time: short-term ( < 30 day), intermediate (30 to 360 day), or long-term ( > 360 days) survival. We used chi-square and Kruskal-Wallis tests for descriptive statistics. Cut-off points of continuous variables were determined by ROC curve. Predictors of survival were analyzed by logistic regression models. Results: The cohort consisted of 29 males and 8 females with a median age of 75 years (IQR 68-79), and median follow-up of 5.6 months (IQR 0.5-14.9). The median time from ICI start to myocarditis onset was 50 days (IQR 36-91). Ten, 14, and 13 patients were in the short-term, intermediate, and long-term survival groups, respectively. By univariate analysis, predictors of long-term survival included initial NT-proBNP ≤ 450, NLR ≤ 4.44, ALC ≥ 1122, normal EKG QTc interval (≤ 450 ms in male or ≤ 460 ms in female), and TnT decrement ≥ 42% by day 8 of immunosuppression (Table 1). All patients with long-term survival presented with a normal left ventricular ejection fraction (LVEF ≥ 55%), which made it uninterpretable using logistic regression models. Normal LVEF was significantly associated with long-term survival by using chi-square test (p = 0.002). While TnT elevation > 75x the upper limit of normal (ULN) was strongly associated with short-term survival (p = 0.001), it was not associated with long-term survival (p = 0.23). The use of second-line immunosuppression in addition to corticosteroids did not have a significant impact on long-term survival (p = 0.69). Conclusions: NLR, ALC, NT-proBNP, QTc interval, and a substantial decrease in TnT at day 8 after immunosuppression are all associated with long-term survival in ICI myocarditis. [Table: see text]
Pancreatic-enzyme replacement therapy with pancrelipase plus chemotherapy for patients with pancreatic adenocarcinoma with cachexia and exocrine pancreatic insufficiency (PANCAX-3).
Authors: Ebia Matthew , Kabir Shaowli , Minton Brian , Abbas Anser Ali , Osipov Arsen , Gong Jun , Hendifar Andrew Eugene 
Published: June 2024

e24059 Background: Pancreatic-enzyme replacement therapy (PERT) is the standard of care to prevent maldigestion, malnutrition, and excessive weight loss in patients with exocrine pancreatic insufficiency (EPI). The utility of this therapy for patients with EPI in the setting of pancreatic ductal adenocarcinoma (PDAC) is unclear. We report results of a single site phase 2 trial for PERT with Pancreaze® plus standard of care (SOC) chemotherapy in PDAC patients with cachexia and EPI. The primary outcome measure was to assess feasibility of completing PERT during the first 8 weeks of treatment. Secondary outcome measures included weight stability, mean change in stool frequency, stool consistency from Cycle 1 (C1) to Cycle 3 (C3) (after 8 weeks of PERT), mean change in serum levels of fat soluble vitamins (A, D, E, K) from baseline to end of study, functional activity, and safety. Methods: Feasibility was defined as adherence to therapy of ≥50% of the needed total lipase units in the first 8 weeks of treatment (84,000 IU lipase units per meal, 42,000 IU lipase units per snack). Data are presented as frequencies (%) for categorical variables and means ± standard deviation for continuous variables. Weight stability, stool frequency, fat soluble vitamin levels, walk speed, and hand grip strength compared using two-sample paired t-tests. Stool consistency (Bristol stool type) compared using Fisher’s exact test. Results: Of 36 patients enrolled, 30 were evaluable for primary endpoint. Median age was 70. 73.3% (22/30) were female. 33.3% (10/30) were borderline resectable, 33.3% (10/30) locally advanced, and 33.3% (10/30) advanced/metastatic. 30 patients completed 8 weeks of PERT and 96.7% (29/30) were compliant. Efficacy results include PR (6.7%, 2/30), SD (66.7%, 20/30) and PD (23.3%, 7/30). Imaging not available for 1 patient. 6 patients experienced grade 1/2 GI toxicities (nausea, bloating, diarrhea, abdominal pain) deemed possibly/probably related to PERT. Grade 3/4 AEs included fatigue, infection, and hematologic toxicities deemed unrelated to PERT. Among evaluable patients, weight remained stable (-0.01±0.07 kg/BMI, p = 0.511) and there was a trend toward reduced stool frequency (p = 0.052) from C1 to C3. Stool consistency from C1 to C3 showed significant association (p = 0.035). Serum fat soluble vitamins, functional activity by walk speed and hand grip strength were also explored and no statistically significant differences were observed from C1 to C3 among the evaluable patients. Conclusions: PERT plus SOC chemotherapy for PDAC patients with cachexia and EPI is feasible and well-tolerated. Patients taking PERT experienced weight stability. PERT may aid in reducing stool frequency and further analysis is warranted into how PERT affects stool consistency. Clinical trial information: NCT04098237 .
Patterns of referral to supportive oncology (SO) practice embedded in a cancer center and impact of timing of referrals on end-of-life outcomes.
Authors: Crowley Fionnuala , Zeng Li , Sheng Tianxiang , Bilani Nadeem , Hobensack Mollie , Popp Beth , Afezolli Debora , Kelly Lauren , Wey Winston , Chen Joanna , Austin Vanessa , Bajwa Aleena , Easton Eve , Pagala Arlyn , Kim Emily , Smith Cardinale B. , Gelfman Laura P. 
Published: June 2024

e24064 Background: ASCO guidelines recommend early palliative care (PC) for patients with advanced cancer, defined as within eight weeks of diagnosis, to enhance survival and quality of life. It is unclear which subsets of patients are referred “late” to PC and how timing of referral impacts cancer outcomes and end-of-life care. Methods: Patients >18 years with first SO consult between 01/01/2021-06/30/2023 were included. Data on patient demographics, acute healthcare and hospice utilization, cancer treatment and mortality was extracted from the electronic medical record (EMR) and claims database. Early referral to SO was defined as visit < 3 months after diagnosis of advanced disease, delayed referrals > 3 months and late consults as < 30 days from death. We used descriptive statistics to describe patients’ sociodemographics, clinical characteristics and healthcare utilization. Multinomial logistic regression analysis was utilized to evaluate how patient characteristics influenced the timing of referrals. To examine the effects of late referral on inpatient (IP) and intensive care unit (ICU) stay durations, we applied a hurdle model. Results: Total sample included 1229 patients; majority had ECOG < 2 and received one line of treatment at time of consult, 87% had solid tumors, of whom 74% had stage 4 disease. The solid tumors most referred were gastrointestinal cancers (25%), lung cancer (14%) and head and neck cancers (13%). Early referral rates across cancer groups differed significantly 53% Head and Neck, 48% GI, 46% Lung, 43% GYN, 29% GU, 11% Breast, and 31% Other (p < 0.001). The most common reason for referral was physical symptom management (98%). The median ESAS symptom burden was 5 (range 0-10) symptoms. At time of analysis, 431 (35.1%) patients had died of which 256 (59%) were in-hospital deaths. Of the deceased patients, late referral ( < 30 days from death) showed a trend, although not statistically significant, toward higher in-hospital mortality rates, (Odds Ratio: 1.13; 95% CI: 0.57-2.24), and a trend toward reduced likelihood of hospice enrollment(Odds Ratio: 0.73; 95% CI: 0.36-1.49). Notably, late referral significantly increased the duration of IP stays (p < 0.001) and ICU stays (p = 0.004) in last 30 days of life, without change in admission to IP (p = 0.68) or ICU (p = 0.86). Conclusions: The delivery of the guideline-directed "early” consult among patients with advanced cancer is variable. Preliminary analysis showed a trend towards higher in-hospital mortality rates and lower hospice referral for patients referred < 30 days from death among “late” consults. Further subgroup analysis is ongoing. [Table: see text]
Examining emerging trends in palliative care utilization for malignant neoplasms with the highest mortality rates.
Authors: Nnawuba Kingsley Chinonyerem , Jensen Hanna , Citla Sridhar Divyaswathi 
Published: June 2024

e24066 Background: Lung, colorectal, pancreatic, breast & prostate cancer account for the top 5 malignancies resulting in mortality in the US. The need for palliative care in patients with these malignancies continues to grow & monitoring its utilization is crucial, especially among different racial groups & ethnicities. Methods: In this study, the TriNetX database which is a collaboration between; pharmaceutical companies, research organizations & HCOs was used. A total of 3,221,731 de-identified pts (pediatric, AYA & adult) was analyzed. The impact of palliative care use vs absence between 2009-2023 was compared in 4-year cohorts, with univariate & multivariate analyses. A p-value < 0.05 was deemed significant. Chi-square was employed to assess palliative care utilization or absence through the years for each group. Results: Analyzing Table 1, palliative care utilization was greater among Non-Hispanics and Whites, as evidenced by the mean. White pts consistently exhibit a higher use compared to other racial groups, but it declined between 2019-2023. The lowest use of palliative care was among Native Hawaiians, Native Americans, & Asians. Black, Latino, Other race, Unknown Race & unknown ethnicity pts accounted for about 50% of its use. Similarly, in most racial & ethnic groups a decline in its non-utilization was observed progressively. Based on the chi-square test, overall results show a significant P-value for all racial & ethnic groups through the years, except for white pts with a p-value of 0.1847. Conclusions: The study highlights disparities that exist in palliative care utilization among racial & ethnic groups. Despite increasing trend in its use, its utilization remains constant among minorities. These details are pivotal in advancing an inclusive healthcare that enhances end of life outcomes for all patients. [Table: see text]