Times Higher Mortality Research Articles

The impact of type 2 diabetes on short term myocardial morphological, functional, and energetic recovery post coronary artery bypass surgery in patients with ischemic heart disease

Abstract Background Type 2 diabetes (T2D) confers three times higher mortality in patients with ischemic heart disease (IHD). Moreover, amongst patients with IHD those with diabetes were shown to have higher long-term mortality from heart failure despite angiographic or surgical revascularisation with coronary artery bypass grafting (CABG). Impaired myocardial structural, functional, and energetic recovery may underpin this epidemiological observation. Consequently, using cardiovascular magnetic resonance and phosphorus-magnetic resonance spectroscopy scans, we aimed to assess the effect of T2D comorbidity on myocardial structural, functional, perfusion, and energetic recovery post-CABG in patients with IHD. Methods Seventy-seven IHD patients with (n=39) and without T2D (n=38) awaiting CABG were recruited. One-month pre- and 6-months post-CABG, cardiac phosphocreatine to ATP ratio (PCr/ATP), global longitudinal shortening (GLS) and 6-minute walk-distance (6MWD) were assessed in the study cohorts. The rest and adenosine-stress myocardial blood flow (MBF) assessments were only performed 6-months post-CABG. Results Pre-CABG, IHD-T2D patients had higher LV concentricity (LV mass to LV end diastolic volume ratio) (IHD-T2D:0.84[0.74,0.93],IHD-noT2D:0.72[0.67,0.77]g/mL,P=0.03]. worse PCr/ATP T2D (IHD-T2D:1.5[1.4,1.7],IHD-noT2D:1.8[1.6, 2.0];P=0.03) and shorter 6-minute walk distance (IHD-T2D:338[307,370],IHD-noT2D:399[364,434]m,P=0.007). There were no significant differences in LV volumes, ejection fraction or GLS between the two groups pre-CABG. Post-CABG, there was no longer a significant difference in cardiac energetics or 6-minute walk distances between the two groups due to a significant improvement in PCr/ATP in the IHD-T2D group. LV concentricity remained significantly elevated in the IHD-T2D group post CABG (IHD-T2D:0.82[0.75,0.88],IHD-noT2D:0.73[0.68,0.79]g/mL,P=0.04). Neither group showed a significant change in LVEF or GLS from the pre-CABG values, and post-CABG there were no differences in the rest or stress myocardial blood flows between the two groups. Conclusions Six months after CABG, neither IHD patients with T2D, nor IHD patients without T2D show any significant changes in LV structural remodelling or in contractile function. T2D does not jeopardise the short-term recovery in myocardial energetics or exercise distance post-CABG, with IHD patients with T2D showing more pronounced improvements post-CABG in both these assessments than patients without T2D. Larger longitudinal studies are needed to better understand the mechanisms of adverse longer-term cardiovascular outcomes suggested by epidemiological studies in IHD patients with T2D.

The impact of the bluetongue serotype 3 outbreak on sheep and goat mortality in the Netherlands in 2023

In September 2023, bluetongue virus serotype 3 (BTV-3) emerged in the Netherlands, infecting over five thousand livestock farms. In sheep, high morbidity and mortality rates were reported that were unlike previously described bluetongue outbreaks. This study aimed to quantify the impact of BTV-3 in the small ruminant population in the Netherlands in 2023. Sheep and goat movement census data and BTV-3 notification data were available from 2020 until the end of 2023. Data were aggregated to farm and week level and mortality indicators were calculated for lambs (<1 year) and adult animals (≥1 year). Population averaged GEE models with a Negative-binomial distribution and a log-link function correcting for repeated measures per farm in time were used to quantify the association between BTV-3 and mortality. In 2023, 2994 sheep farmers and 89 goat farmers notified clinical signs of BTV-3 to the NVWA. During this BTV-3 outbreak period, an additional 55,000 sheep died compared to the same period in 2020–2022. At flock level a high variety in mortality was observed, with a clear increase in mortality in both flocks that were not notified but that were located in infected areas and in flocks of which the farmer notified clinical signs. During the BTV-3 outbreak period, mortality in infected areas increased 4.2 (95 % CI: 4.0–4.3) times in sheep lambs (<1 year) and 4.6 (95 % CI: 4.4–4.8) times in sheep (≥1 year) compared to BTV-3 free areas. Flocks with a confirmed BTV-3 infection that were notified in September showed a 12.8 (95 % CI: 11.4–14.3) times higher mortality in lambs and a 15.1 (95 % CI: 13.7–16.6) times higher mortality in sheep compared to flocks in BTV-3 areas. In flocks of which the farmer notified clinical signs after September, mortality was 4.6 (95 % CI: 4.2–5.0) and 5.6 (95 % CI: 5.1–6.0) times higher in lambs and sheep compared BTV-3 areas respectively. In goats, around 4000 additional deaths were recorded during the BTV-3 outbreak period. In farms that were notified, mortality of goats (≥1 year) was 1.8 (95 % CI: 1.2–2.8) times higher compared to BTV-3 free areas. Since May 2024, multiple BTV-3 vaccines are available in the Netherlands. In June 2024, the first new infections of BTV-3 were confirmed in Dutch sheep flocks. Hopes are that with the possibility to vaccinate, the spread and impact of BTV-3 in the Netherlands will rapidly decline and that losses as observed in 2023 will no longer be seen.

Association of Abnormal Cardiac Biomarkers and Cardiovascular Complications, with Mortality in Patients with SARS-CoV-2 Infection in Latin America.

The COVID-19 pandemic has highlighted a correlation between cardiac complications and elevated cardiac biomarkers, which are linked to poorer clinical outcomes. This study aims to determine the clinical impact of cardiac biomarkers in COVID-19 patients in Latin America. The CARDIO COVID 19-20 Registry is a multicenter observational study across 44 hospitals in Latin America and the Caribbean. It included hospitalized COVID-19 patients (n = 476) who underwent troponin, natriuretic peptide, and D-dimer tests. Patients were grouped based on the number of positive biomarkers. Among the 476 patients tested, 139 had one positive biomarker (Group C), 190 had two (Group B), 118 had three (Group A), and 29 had none (Group D). A directly proportional relationship was observed between the number of positive biomarkers and the incidence of decompensated heart failure. Similarly, there was a proportional relationship between the number of positive biomarkers and increased mortality. In Group B, patients with elevated troponin and natriuretic peptide and those with elevated troponin and D-dimer had 1.4 and 1.5 times higher mortality, respectively, than those with elevated natriuretic peptide and D-dimer. In Latin American COVID-19 patients, a higher number of positive cardiac biomarkers is associated with increased cardiovascular complications and mortality. These findings suggest that cardiac biomarkers should be utilized to guide acute-phase treatment strategies.

Does improved nurse staffing impact patient outcomes in cancer? Association between chronic diseases and mortality among older adult patients with lung cancer in Korea.

Evidence regarding the impact of nurse staffing on the health outcomes of older adult patients with cancer is scarce. Therefore, this study aimed to evaluate the impact of nurse staffing on long-term and short-term mortality in elderly lung cancer patients. This study analyzed data from 5,832 patients with lung cancer in Korea from 2008 to 2018. Nursing grade was considered to assess the effect of nursing staff on mortality in older adult patients with lung cancer. The Cox proportional hazards model was used to evaluate the effect of the initial treatment hospital's nursing grade on one- and five-year mortality. Additionally, economic status and treatment type of patients were analyzed. Approximately 31% of older adult patients with lung cancer died within one year post-diagnosis. Patients in hospitals with superior nursing grades (lower nurse-to-bed ratios) exhibited lower mortality rates. Hospitals with nursing grades 2 and 3 exhibited approximately 1.242-1.289 times higher mortality than grade 1 hospitals. Further, the lower the nursing grade (higher nurse-to-bed ratio), the higher the five-year mortality rate. Both short- and long-term mortality rates for older adult patients with lung cancer increased at inferior nursing grades. Treatment in hospitals having inferior nursing grades, upon initial hospitalization, may yield better outcomes. This study provides valuable insight into the quality of adequate staffing to improve the quality of care for elderly cancer patients.

Evaluation of the Possible Benefits of Breast Cancer Screening in Women Aged 40 to 49 Years in the Steel Valley Region, Brazil

Background: This study investigates the effectiveness of mammographic screening for women aged 40 to 49 in Brazil's Steel Valley Region. Despite a Ministry of Health recommendation to start screenings at 50, 25% of breast cancer cases occur in the 40-49 age group. Methods: The retrospective analysis, spanning 2008-2019 at Marcio Cunha Hospital, compared two groups: cancer diagnosed via screening mammography (277) and diagnostic mammography (229). Results: Results showed delayed diagnoses for non-screened women, with 4.16 times higher mortality rate. Screening facilitated earlier detection of less malignant cancers (85.9% vs. 43.7%). Women diagnosed through screening were more likely to preserve their breasts (28.9% vs. 55.5% for Radical Breast Surgery and 71.1% vs. 28.9% for Breast-Sparing Surgery), and fewer axillary lymphadenectomies were performed. All statistical tests performed returned a p-value lower than 0.05 showing high statistical significance. Conclusion: The findings support extending screening mammography access to all women over 40 in the Steel Valley region and underscore the need for broader-scale research in other areas. Recommendations include enhancing public awareness and establishing a breast cancer surveillance service.

Abstract 7645: Differentially expressed genes as prognostic markers in racial disparities of prostate cancer

Abstract Racial disparities in prostate cancer are prevalent, with African American (AA) men experiencing 60% greater incidence and 2 to 3 times higher mortality than Caucasian American (CA) men. Consequently, there is a pressing need for improved means of interrogating race/ethnicity-based prostate cancer biology in order to identify biomarkers to help stratify men at high-risk for prostate cancer-specific progression and death and offer treatment recommendation that would mostly benefit AA men undergoing early aggressive therapies. Current predictive models rely on clinical variables but do not account for these disparities. The overall goal is to construct a race-specific prostate cancer prognostic prediction model for risk assessment. Here we performed comprehensive bioinformatics analysis using the data from 17 pairs of gene expression array from AA and CA cohorts and identified 63 differentially expressed genes (DEGs) by race. Among them, chemokine receptor 4 (CXCR4), viz. p-Akt (Ser473), fatty acid synthase (FASN), interleukin-6 (IL-6) and matrix metallopeptidase 9 (MMP-9) gene expressions were significantly altered in AA groups. Immunohistochemistry was performed on 163 prostate cancer patient specimens to validate DEG expression and immunoreactive scores (IRS) were calculated. CXCR4 exhibited significantly higher expression in AA tumors, with &amp;gt; 85% of AA prostate tumors showing weak to strong CXCR4 expression, compared to &amp;lt; 5% in CA specimens. While immunostaining for IL-6, FASN, MMP9 and p-Akt did not provide a significant distinction between CA and AA cases. IRS analysis confirmed higher expression of CXCR4 in AA cancers, compared to CA prostate cancer (p &amp;lt; 0.001). MMP9 and IL6 expression were moderately higher in AA cancer compared to CA prostate cancer (p &amp;lt; 0.05). In contrast, FASN expression was significantly higher in CA cancer, compared to AA prostate cancer (p &amp;lt; 0.001). We further investigated the impact of these genes on biochemical recurrence-free survival (BCRFS) using Kaplan-Meier analysis to examine the differences between low-risk versus high-risk groups. BCRFS analysis demonstrated that CXCR4 is a determinant factor of recurrence risk in AA prostate cancer patients. The activation of the PI3K-Akt signaling pathway, particularly in AA patients, suggests its role in prostate cancer aggressiveness. Taken together, this study demonstrates the importance of differential expression of biomarkers which constitute the bulk tumors in driving cancer. The distinct gene expression patterns, especially the upregulation of CXCR4, in AA prostate cancer highlight its potential as a prognostic biomarker and a target for personalized treatment strategies. These findings encourage further study into the role of population-specific difference in adding CXCR4 in risk model construction, especially in machine learning models. Citation Format: Amel A. Ahmed, Shiv Verma, Ibrahim M. Atawia, Daniel L. Shen, Gregory T. MacLennan, Pingfu Fu, Sanjay Gupta. Differentially expressed genes as prognostic markers in racial disparities of prostate 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 7645.

Self-transfers, Hospital Admissions and Mortality Among Children and Adolescents Lost to Follow-up From Antiretroviral Therapy Programs in the Western Cape, South Africa Between 2004 and 2019: Linkage to Provincial Records.

Pediatric programs face a high rate of loss to follow-up (LTFU) among children and adolescents living with HIV (CAHIV). We assessed true outcomes and predictors of these among CAHIV who were LTFU using linkage to the Western Cape Provincial Health Data Centre at Western Cape sites of the International epidemiology Databases to Evaluate AIDS-Southern Africa collaboration. We examined factors associated with self-transfer, hospital admission and mortality using competing risks regression in a retrospective cohort of CAHIV initiating antiretroviral therapy <15 years old between 2004 and 2019 and deemed LTFU (no recorded visit at the original facility for ≥180 days from the last visit date before database closure and not known to have officially transferred out or deceased). Of the 1720 CAHIV deemed LTFU, 802 (46.6%) had self-transferred and were receiving care elsewhere within the Western Cape, 463 (26.9%) had been hospitalized and 45 (2.6%) CAHIV had died. The overall rates of self-transfer, hospitalization, mortality and LTFU were 9.4 [95% confidence interval (CI): 8.8-10.1], 5.4 (95% CI: 5.0-6.0), 0.5 (95% CI: 0.4-0.7) and 4.8 (95% CI: 4.4-5.3) per 100 person-years respectively. Increasing duration on antiretroviral therapy before LTFU was associated with self-transfers while male sex, older age at last visit (≥10 years vs. younger) were associated with hospital admission and immune suppression at last visit was associated with 5 times higher mortality. Nearly half of CAHIV classified as LTFU had self-transferred to another health facility, a quarter had been hospitalized and a small proportion had died.

Assessing the excess costs of the in-hospital adverse events covered by the AHRQ's Patient Safety Indicators in Switzerland.

There currently exists no comprehensive and up-to date overview on the financial impact of the different adverse events covered by the Patient Safety Indicators (PSIs) from the Agency for Healthcare Research and Quality. We conducted a retrospective case-control study using propensity score matching on a national administrative data set of 1 million inpatients in Switzerland to compare excess costs associated with 16 different adverse events both individually and on a nationally aggregated level. After matching 8,986 cases with adverse events across the investigated PSIs to 26,931 controls, we used regression analyses to determine the excess costs associated with the adverse events and to control for other cost-related influences. The average excess costs associated with the PSI-related adverse events ranged from CHF 1,211 (PSI 18, obstetric trauma with instrument) to CHF 137,967 (PSI 10, postoperative acute kidney injuries) with an average of CHF 27,409 across all PSIs. In addition, adverse events were associated with 7.8-day longer stays, 2.5 times more early readmissions (within 18 days), and 4.1 times higher mortality rates on average. At a national level, the PSIs were associated with CHF 347 million higher inpatient costs in 2019, which corresponds to about 2.2% of the annual inpatient costs in Switzerland. By comparing the excess costs of different PSIs on a nationally aggregated level, we offer a financial perspective on the implications of in-hospital adverse events and provide recommendations for policymakers regarding specific investments in patient safety to reduce costs and suffering.

Healthcare‐Associated Infections’ Characteristics Among Burn Patients and Risk Factors of Mortality: A Study Based on Data From a Tertiary Center in Iran

Background: Burn patients are more likely to get healthcare‐associated infections (HAIs). The current study aimed to investigate the characteristics of HAI and mortality risk factors among burn patients admitted to a tertiary center in Iran.Methods: A retrospective study was conducted in 2021 on burn patients who developed HAI after hospitalization in a tertiary center in Ahvaz, Iran. The records of patients admitted and managed between March 2019 and March 2020 were reviewed. Statistical analysis was carried out using IBM SPSS Version 26, with p &lt; 0.05 considered statistically significant.Results: Of the 1,659 admitted patients, 395 (23.8%) developed HAI during the study period. After excluding patients with incomplete medical records and those with fungal or viral infections, 363 patients remained. The majority of these cases occurred in male patients. The most common type of HAI was burn wound infection (56.2%). Patients were mainly affected by Gram‐negative bacteria, Pseudomonas aeruginosa (39.7%), while the most common Gram‐positive bacteria was Staphylococcus epidermididis (9.6%). The most common antibiotic resistance among P. aeruginosa‐infected patients was reported against imipenem, followed by gentamicin and ciprofloxacin; however, the mentioned organism was mainly sensitive to colistin. Gender, age, bloodstream infection (BSI), ventilator‐associated infection (VAI), ICU admission, and total burned surface area (TBSA) resulted in 3.585, 1.028, 2.222, 7.469, 5.278‐, and 1.031 times higher mortality rates, respectively.Conclusion: Female gender, advanced age, BSI, VAI, and ICU admission are risk factors for HAI. These findings emphasize the need for focused infection prevention and management to improve high‐risk burn patient survival.

Establishing a clinically applicable frailty phenotype screening tool for aging dogs.

Frailty is a well-defined clinical syndrome in humans caused by accumulation of impairments which result in loss of reserve capacity and increased vulnerability to disability, dependence, and death. Dogs are of particular interest in studies of frailty due to the similarities they share with people in their environment, lifestyles, and age-related diseases. The aim of this study was to develop a frailty phenotype screening tool, based on previously validated measures in dogs, which could be easily applied in the clinical setting, and which was predictive of all-cause, short term (6-month) mortality. The study was conducted in two phases. In phase 1, a retrospective cohort of 51 dogs was used to identify and evaluate potential measures for the five domains of frailty. This information was then used to develop a simple frailty phenotype based on examination findings and owner directed questions. In phase 2 of the study, this phenotype was evaluated in a prospective cohort of 198 dogs aged 9 years or older from multiple different specialty and primary care services to determine how the phenotype performed across a diverse canine population. The developed frailty phenotype was predictive of all-cause, short-term mortality independent of age, sex, or weight (hazard ratio = 4.71; 95% CI, 2.66-8.8). Of the covariates evaluated only breed was significant, with purebred dogs having 1.85 times higher mortality than mixed breed dogs (95% CI, 1.04-3.31). The frailty phenotype performed similarly across all hospital services from which patients were enrolled. Based on these findings, the defined frailty phenotype represents a valuable screening tool for early risk identification and intervention, and can aid in clinical decision making for owners and veterinarians. Additionally, it will promote further research into the understanding and treatment of frailty in dogs.

COMPARING THE ASSOCIATION BETWEEN DIABETES AND MORTALITY IN TWO INDEPENDENT BIRTH COHORT OF OLDER ADULTS IN MEXICO

Abstract The prevalence of diabetes among middle-aged and older adults in Mexico has nearly doubled since the year 2000. This increase is primarily due to healthcare reforms that promoted diabetes screening. Insulin use and other treatments have also increased during the same period. Early diagnosis and treatment can reduce diabetes mortality risk. However, it is unclear if the increased diagnosis and treatment of diabetes in Mexico have reduced the mortality risk associated with diabetes in older adults. We used the Mexican Health and Aging Study to compare the association between diabetes and 5-year mortality in two independent cohorts of adults aged 60-69 in 2001 (1932-1941) and 2012 (1943-1952). The final sample included 3,694 participants in 2001 and 4,769 in 2012. Demographic variables included age, gender, education, living in an urban community, and having health insurance coverage. Self-reported health conditions included diabetes, hypertension, stroke, and respiratory disease. We used cox-proportional hazard regression models that included an interaction term for diabetes by cohort and adjusted for demographic and self-reported health characteristics. Overall, diabetes was associated with 2.56 times higher mortality (95% CI=2.18-3.00). The 2012 cohort did not have significantly different mortality risk compared to the 2001 cohort (HR=0.91, 95% CI=0.77-1.07). The association between diabetes and mortality for participants in the 2001 cohort (HR=2.52, 95% CI=1.95-3.26) was not significantly different from the 2012 cohort (HR=2.58, 95% CI=2.09-3.17). Our results indicate that diabetes continues to be a major risk factor for mortality in Mexico despite the increase in screening and treatment.

Is an uncomplicated postoperative recovery following total pelvic exenteration a more important prognostic factor than achieving R0 in the first 2 years?

Total pelvic exenteration (TPE) can achieve an R0 resection in locally advanced and recurrent rectal cancer (LARC and RRC) and remains the only curative option. The resultant high morbidity creates prolonged complex recoveries, rendering patients unfit for adjuvant chemotherapy. This study aims to evaluate the impact of this on overall survival (OS) and disease-free survival (DFS) as it has not been studied previously. This is a retrospective single-centre study from 2017 to 2021 evaluating patients with LARC or RRC who underwent a curative TPE. Demographics, oncological history, perioperative data [using Clavien-Dindo (CD) scoring], disease recurrence and mortality were analysed using multivariate Cox regression to assess the impact of variables on DFS and OS. A total of 120 patients were included with a median follow-up of 3 years. 28% of patients received adjuvant chemotherapy, 27.5% had surgical follow-up and 44% missed systemic treatment. Missed treatment was predominantly due to prolonged recovery or poor performance status (59%). Patients who missed adjuvant chemotherapy experienced significantly higher CD scores (p = 0.0031), reintervention rates (p=0.0056) and further related surgeriesp (p = 0.0314). Missing adjuvant chemotherpy is a significant factor for poorer survival, with almost a three times higher mortality (p=0.0096, hazard ratio 2.7).R status was not a significant factor for OS following multivariate analysis (p = 0.336), indicating that another factor has an impact on survival within the first 2 years. In the initial 2 years after exenteration, an uncomplicated postoperative recovery allows for the delivery of adjuvant chemotherapy, prolonging survival. R0/R1 status was not the main prognostic factor. Longer follow-up and further multivariate analysis may influence decisions about aggressive R0 resection balanced against the patient being fit for chemotherapy postoperatively.

Abstract B025: A multi-omic, spatial approach using patient prostatectomies to identify actionable drug targets for combatting prostate cancer health disparities

Abstract Prostate cancer (PC) is the most commonly diagnosed cancer among African American men (AA) and continues to be the largest difference in absolute incidence and cancer-specific deaths between AA and Caucasian men (CA). AA have a 70% higher incidence of PC than CA and over a 2 times higher mortality rate. Among men undergoing prostate biopsy In an equal access setting (i.e. the VA), AA are ~50% more likely to have PC and ~80% more likely to have high-grade PC than CA. The frequency of PC-associated genetic alterations and differences in oncogene expression in PCs is altered from CA and AA. While social economic status and environmental factors may play a role in PC health disparities, there are inherent genetic/molecular differences that account for the differences in PC outcomes between CA and AA. We sought to test our hypothesis that there is a subset of actionable gene products that are essential for enhanced PC progression in AA. A focused and clinically informed CRISPR knockout screen was conducted to identify and functionally validate race-specific actionable genes that contribute to the increased risks of fatal PC in AA. The CRISPR screen was designed leveraging a radical prostatectomy transcriptomic dataset from the Durham VA Medical Center that was linked with long-term clinical outcome data. This unique dataset consists of ~600-profiled radical prostatectomy samples of which over 50% were from AA patients. A Cox hazard analysis revealed differentially expressed genes (DEGs) which are positively associated with an increased risk of metastatic disease unique to AA PC patients. To identify drug-targetable genes, these DEGs were filtered against the drug-gene interaction database (DGIdb). This approach yielded 89 genes positively associated with an increased risk of metastatic outcome in AA and 236 genes in CA only. The CRISPR KO screen resulted in 19 genes significantly depleted genes. Of these 19 hits, 11 genes were genes associated with metastasis in AA, while 8 hits were CA genes, with 5 of 11 AA hits having documented small molecule inhibitors. To further prioritize our hits, we have conducted a spatial transcriptomic analysis of radical prostatectomy tissues from AA and CA PCs. By standard H and E staining these tumors look quite similar. But spatial analysis of AA compared to CA tissues revealed differences in immune cells and cells associated with the tumor microenvironment. This integrative multi-omic approach reveals new cell identities that may contribute to the aggressive pathogenicity of PC in AA compared to CA. CRISPR models and small molecule inhibitors of our top candidates will be used to investigate the druggability of these DEGs. This study lays the groundwork for potential therapeutics targeted toward PC in AA men. Citation Format: Felipe Segato Dezem, Aiza Akhtar, Arjumand Wanj, Sunyoung You, Hannah Chasteen, So Young Kim, Jasmine Plummer, Everardo Macias. A multi-omic, spatial approach using patient prostatectomies to identify actionable drug targets for combatting prostate cancer health disparities [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B025.

Abstract IA047: A multiomic approach towards identifying actionable targets to combat prostate cancer health disparities

Abstract Prostate cancer (PC) is the most commonly diagnosed cancer among African American men (AA) and continues to be the largest difference in absolute incidence and cancer specific deaths between AA and Caucasian men (CA). AA have a 70% higher incidence of PC than CA and over a 2 times higher mortality rate. Among men undergoing prostate biopsy In an equal access setting (i.e. the VA), AA are ~50% more likely to have PC and ~80% more likely to have high-grade PC than CA. The frequency of PC associated genetic alterations and differences in oncogene expression in PCs is altered from CA and AA. While social economic status and environmental factors may play a role in PC health disparities, there are inherent genetic/molecular differences that account for the differences in PC outcomes between CA and AA. We sought to test our hypothesis that there is subset of actionable gene products that are essential for enhanced PC progression in AA. A focused and clinically informed CRISPR knockout screen was conducted to identify and functionally validate race specific actionable genes that contribute to the increased risks of fatal PC in AA. The CRISPR screen was designed leveraging a radical prostatectomy trancscriptomic dataset from the Durham VA Medical Center that was linked with long-term clinical outcome data. This unique dataset consists of ~600-profiled radical prostatectomy samples of which over 50% were from AA patients. A cox hazard analysis revealed differentially expressed genes (DEGs) which positively associated with increased risk of metastatic disease unique to AA PC patients. To identify drug targetable genes, these DEGs were filtered against the drug gene interaction database (DGIdb).This approach yielded 89 genes positively associated with increased risk of metastatic outcome in AA and 236 genes in CA only. The CRISPR KO screen resulted in 19 genes significantly depleted genes. Of these 19 hits, 11 genes were genes associated with metastasis in AA, while 8 hits were CA genes, with 5 of 11 AA hits have documented small molecule inhibitors. To further prioritize our hits, we have conducted spatial transcriptomic analysis of radical prostatectomy tissues from AA and CA PCs. By standard H and E staining these tumors looking quite similar. But spatial analysis of AA compared to CA tissues revealed differences in immune cells and cells associated with tumor microenvironment. These integative multiomic approach reveals new cell identities that may contribute to the aggressive pathogenicity of PC in AA compared to CA. CRISPR models and small molecule inhibitors of our top candidates will be used in investigate druggability of these DEGs. This study lays the groundwork for potential therapeutics targeted towards PC in AA men. Citation Format: Felipe Dezem, Aiza Akhtar, Sungyong You, So Young Kim, Jasmine Plummer, Everardo Macias. A multiomic approach towards identifying actionable targets to combat prostate cancer health disparities [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr IA047.

Abstract 19142: Is Malnutrition Associated With Worse Outcomes in Patients With Acute Decompensated Heart Failure (ADHF)? ; Insights From Nationwide Inpatient Sample 2015-2020

Introduction: Is Malnutrition associated with worse outcomes in patients admitted with acute decompensated heart failure? Insights from nationwide inpatient sample 2015-2020 Hypothesis: Heart Failure affects &gt;5 million US patients resulting in &gt;1 million annual hospitalizations due to Acute Decompensated Heart Failure (ADHF). The impact of malnutrition on hospitalized patients with ADHF is not well described. Patients with heart failure are prone to malnutrition because of reduced intake, cytokine dysfunction, and increased basal metabolic rate. We aim to assess the effect of malnutrition on hospital outcomes in ADHF. Methods: Using the NIS database we identified all the patients who were admitted for ADHF with history of heart failure with reduced ejection fraction from 2015-2020. Predictors and effects of malnutrition were studied using univariate and multivariate models. Results: A total of 4,224,869 patients were admitted for ADHF from 2015-2020 among which 253,915 patients had associated malnutrition. Baseline characteristics and comorbidities are outlined in the table below. Patients with malnutrition had higher inpatient mortality (9.6% vs 3.61% p-value:0.0000), a longer length of stay (10.8 days vs 5.9 days p-value: 0.0000), doubling of the cost of care (147485 USD vs 74077 USD p-value:0.001). After adjusting for baseline co-morbidities patients with malnutrition had 2 times higher mortality (Odds ratio: 2.01, p-value: 0.0001) Conclusions: Our study demonstrates that Malnutrition in ADHF patients results in higher mortality, longer length of stay, and higher costs of care. This highlights the importance of optimizing of nutritional status in these patients.

Pituitary Diseases and COVID-19 Outcomes in South Korea: A Nationwide Cohort Study.

The pituitary gland is either directly or indirectly impacted by SARS-CoV-2 infection. As a consequence of SARS-CoV-2 infection, hypothalamic-pituitary dysfunction or pituitary apoplexy can occur. This study aimed to investigate severe COVID-19 outcomes and COVID-19-related mortality in patients with underlying pituitary disease in Korea using a nationwide cohort database. The data required for this study were obtained from the Health Insurance Review and Assessment Service of Korea. Patients with SARS-CoV-2 infection between January 2020 and December 2021 were divided into the following three groups and analyzed: Group A, those who were hospitalized for SARS-CoV-2 infection without underlying pituitary disease (n = 725,170); Group B, those who were hospitalized for SARS-CoV-2 infection with underlying pituitary disease without exposure to systemic steroids (n = 1509); and Group C, patients with underlying pituitary disease and exposure to systemic steroids (n = 365). Differences in severe COVID-19, requirement for oxygen therapy, intensive care unit admission, application of invasive ventilation or use of extracorporeal membrane oxygenation, and COVID-19-related deaths between groups were then analyzed. Group C had the highest rates of hospitalization after COVID-19 infection (82.2%) and mortality within 30 days of infection (6.8%). Group B had a 1.3-fold increase in severe COVID-19 outcomes compared to Group A. Group C had 1.8-fold and 1.3-fold increases in severe COVID-19 outcomes compared to Group A and Group B, respectively. Group C also had 2.34 and 3.24 times higher mortality rates within 30 days of COVID-19 infection than Group A and Group B, respectively. In conclusion, patients with pituitary disease who are receiving systemic steroids have poorer outcomes and higher mortality associated with COVID-19. Therefore, thorough COVID-19 infection control is required in these patients.

Predictors of all-cause mortality in hospitalized COVID-19 patients taking corticosteroids: a multicenter retrospective cross-sectional study.

A multicenter retrospective study was performed over three months targeting 422 COVID-19 patients from six hospitals in Lebanon. Data were collected from patients' medical charts retrospectively and covered a period of one year (September 2020-August 2021). The study sample included 422 patients, predominantly males, with 59% of cases classified as severe or critical cases. Dexamethasone and methylprednisolone were the most used corticosteroids. Around 22% of the patients died during hospitalization. After adjusting for covariates, performing a polymerase chain reaction before admission increased the mortality rate by 424% compared to doing it at hospital admission (aHR 4.24, 95% CI 1.35-13.3), with 18.11 times higher mortality rate among critical cases (aHR 18.11, 95% CI 9.63-31.05). Exposure to side effects from corticosteroids increased the mortality rate by 514% compared to others (aHR 5.14, 95% CI 1.28-8.58). In particular, the mortality rate among patients having hyperglycemia dropped by 73% compared to others (aHR 0.27, 95% CI 0.06-0.98). Corticosteroids are frequently used in treating hospitalized COVID-19 patients. The all-cause mortality rate was higher among older and critical cases and lower among smokers and those treated for more than 7 days. Research exploring the safety and efficacy of corticosteroids is required to allow better in-hospital management of COVID-19 cases.

A Regional Analysis of Potentialy Preventable Injuries Sustained from Burning Garbage and Yard Waste.

Due to high prevalence in the south, understanding the injury pattern, healthcare burden, and cost of burn injuries associated with burning yard and trash debris are important for effective prevention. This five-year retrospective, single-center study included patients sustaining an open flame burn injury due to burning brush or trash. Based on primary residence of the 136-patients, 56% had access to free municipal waste disposal, 25% could have had access with additional payment, and 18% did not have access. The median (Q1, Q3) age and total body surface area (TBSA) burned was 50 (32, 66.5) years and 5% (2.5, 12), respectively, with 36% having some portion of full-thickness injury. One-third had some form of substance use. There were 151 total operations with a median of 1 (0, 1.5) per patient. There were 1,620 hospital days utilized (~6.6% of available bed-days per study period). Twenty-five percent were discharged with a paired functional status worse than pre-injury. Patients with some degree of pre-injury function limitations had a three-fold higher length of stay (10 vs 3 days; p = 0.023). Patients with lower pre-injury functionality had almost 4 times higher mortality (23.7% vs 6.3%; p = 0.085). There were 9 (6.7%) deaths with an average (± SD) 74.3 ± 13.1 years of age, median 33% (31, 43) TBSA, and median full-thickness TBSA of 32% (21, 44). Total hospital charges exceeded $32.6 million with a median $32,952.26 ($8,790.48, $103,113.95) per patient. Focusing future outreach efforts on education and resource availability may prevent future waste burning injuries.

Severe thrombocytopenia is associated with high mortality in systemic lupus erythematosus-analysis from Indian SLE Inception cohort for Research (INSPIRE).

Thrombocytopenia in patients with systemic lupus erythematosus (SLE) is associated with higher morbidity and mortality. We report frequency, associations and short-term outcome of moderate-severe thrombocytopenia in a prospective inception cohort from India (INSPIRE). We evaluated consecutive SLE patients classified per SLICC2012 for the occurrence of thrombocytopenia and its associations. The outcomes assessed included bleeding manifestations, kinetics of thrombocytopenia recovery, mortality and recurrence of thrombocytopenia. Among a total of 2210 patients in the cohort, 230 (10.4%) had incident thrombocytopenia, of whom moderate (platelet count [PC] 20-50 × 109/L) and severe thrombocytopenia (PC < 20 × 109/L) were noted in 61 (26.5%) and 22 (9.5%), respectively. Bleeding manifestations were generally limited to the skin. Compared to controls, cases had a higher proportion of autoimmune haemolytic anaemia (p < 0.001), leukopenia (p < 0.001), lymphopenia (p < 0.001), low complement (p < 0.05), lupus anticoagulant (p < 0.001), higher median SLEDAI 2K (p < 0.001) and lower proportion of anti-RNP antibody (p < 0.05). There was no significant difference in these variables between moderate and severe thrombocytopenia. There was a sharp rise in PC by 1week that was sustained in the majority through the period of observation. There was three times higher mortality in the severe thrombocytopenia group as compared to moderate thrombocytopenia and controls. The thrombocytopenia relapse and lupus flare rates were similar across categories. We report a low occurrence of major bleeds and higher mortality in those with severe thrombocytopenia as compared to moderate thrombocytopenia and controls. Key Points • Severe thrombocytopenia occurs in 1% of patients with SLE; however, major bleeds are uncommon. • Thrombocytopenia has a strong association with other lineage cytopenias and lupus anticoagulants. • Response to initial glucocorticoids therapy is quick and is well sustained with additional immunosuppressants. • Severe thrombocytopenia increases mortality threefold in SLE.

P438 DIABETES MELLITUS AND HEART FAILURE: A DANGEROUS ASSOCIATION

Abstract Introduction Diabetes mellitus is a frequent co–morbidity in heart failure patients reaching a prevalence of about 35% and patients with diabetes mellitus are twice as likely as non–diabetics to develop heart failure. The presence of diabetes is associated with higher rates of cardiovascular morbidity and mortality. In recent years, the introduction of remote monitoring systems has allowed for more careful management of them, although there are no large studies demonstrating their effectiveness in terms of improving prognosis. The aim of our study was to evaluate the prognosis of patients with diabetes mellitus and heart failure undergoing remote monitoring. Methods All patients undergoing device implantation for heart failure in our Center were recruited into the study, and the incidence of events (new hospitalizations or hospitalizations) during the period from January 1, 2021 to December 31, 2021 was assessed. Patients were monitored, and direct telephone contact or contact with one of the family members was made for all of them. Data on clinical characteristics and drug therapy were recorded. Results A total of 240 patients (73±11 years, 81% male) of whom 74 were diabetic (73±11 years, 87% male) and 166 were nondiabetic (73±10 years, p=0.82, 80% male, p= 0.198) were enrolled in the study. The two groups had no statistically significant differences in terms of clinical characteristics (such as ejection fraction, NYHA class, presence of anemia, rate of wide QRS, or rate of defibrillator implantation) except for a higher incidence of coronary artery disease in diabetic patients (70%) and multivessel coronary disease (67%) than in non–diabetic patients (57% coronary artery disease p= 0.05, and 46% multivessel disease p= 0.02). There were no significant differences in terms of drugs with the exception of higher use of statins in the group of diabetic patients (84%) compared to non–diabetics (64%, p= 0.002). Diabetic patients had almost 4 times higher mortality rates than non–diabetic patients (22% and 6% respectively, p&amp;lt; 0.0001). Differently, hospitalization rates were not significantly different among diabetic patients (24%) compared with nondiabetic patients (28%, p= 0.58). Conclusions The association of diabetes mellitus and heart failure represents a dangerous combination associated with an increased incidence of death. Therefore, clinical monitoring strategies and intensity of drug therapy should be particularly implemented in diabetic patients.