Significant Increase In Mortality Research Articles

18. RISK FACTORS FOR EVISCERATION IN PATIENTS UNDERGOING MIDLINE LAPAROTOMY AT A TERTIARY HOSPITAL

Abstract Introduction Evisceration is a frequent complication in patients undergoing median laparotomy that results in a significant increase in morbidity and mortality, hospital stay and healthcare expenditure. Numerous risk factors associated with the appearance of this complication have been described without being able to determine the individual influence of each one of them. Our aim is to describe the most frequent risk factors in our sample. Methods We retrospectively collected all eviscerations registered in our center between January 1, 2010 and December 31, 2020 in patients undergoing median laparotomy. Seventy-five cases were recruited. Seventy-five controls undergoing median laparotomy in the same time period were collected and associated risk factors were analyzed. Results The risk factors that were statistically significant were male sex (protective factor with OR 6.4 CI95% 3.4-7.6), COPD (OR 5.6 CI95% 1.69-19.9), surgical wound infection (OR 3.49 CI95% 1.86-14.1), ileus (OR 14.7 CI95% 1.66-131.40) and anastomotic dehiscence (OR 7.58 CI95% 1.76-32.50). No statistically significant differences were found between the different types of sutures used for abdominal wall closure. 92% of the cases underwent surgical repair, 8% were managed conservatively. Postoperative mortality was 16%. Conclusion The occurrence of evisceration appears to be related to risk factors associated with the patients' pre-existing comorbidities and postoperative complications.

Single-Center Experience with Therapeutic Hypothermia for Hypoxic Ischemic Encephalopathy in Infants < 36 Weeks Gestation.

Hypoxic ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in neonates. Therapeutic hypothermia (TH) has improved outcomes and mortality in infants >36 weeks gestational age (GA) with moderate-to-severe HIE. There are limited data on the safety and efficacy of TH in preterm infants with HIE. This study describes our experience and examines the safety of TH in neonates <36 weeks' GA. A single center, retrospective study of preterm neonates born <36 weeks' GA with moderate-to-severe HIE and treated with TH, compared to a cohort of term neonates with HIE (≥37 weeks' GA), was conducted. The term cohort was matched for degree of background abnormality on EEG, sex, inborn vs. outborn status, and birth year. Medical records were reviewed for pregnancy and delivery complications, need for transfusion, sedation and antiseizure medications, electroencephalography and imaging findings, and in-hospital mortality. Forty-two neonates born at <36 weeks' GA with HIE received TH between 2005-2022. Data from 42 term neonates was analyzed for comparison. The average GA of the preterm cohort was 34.6 weeks and 39.3 weeks for the term cohort. Apgar scores, degree of acidosis, and need for blood product transfusions were similar between groups. Preterm infants were more likely to require inotropic support (55% vs 29%, p=0.026) and hydrocortisone (36% vs 12%, p=0.019) for hypotension. The proportion of infants without evidence of injury on MRI was similar in both groups: 43% vs. 50% in preterm and term infants, respectively. No significant difference was found in mortality between groups. In this single-center cohort, TH in preterm infants appears to be as safe as in term infants, with no significant increase in intracranial bleeds or mortality. Preterm infants more frequently required inotropes and steroids for hypotension. Further research is needed to determine efficacy of TH in preterm infants.

Sarcoidosis. A review of diagnosis, clinical features and treatment

Introduction: Sarcoidosis is a progressive chronic multisystemic inflammatory disease of unclear pathogenesis, which presents with noncaseating granulomas and is complicated to diagnose due to the variable clinical presentation of patients. Sarcoidosis may attack any organ, but especially the pulmonary, cutaneous, lymphatic, ocular, hepatic and splenic systems. The most frequent presentations are prolonged cough, rash, visual problems, peripheral lymphadenopathy, tiredness, and occasional abnormality of the chest X-ray. The diagnostic evaluation of sarcoidosis is difficult and often involves a combined effort of clinical data and appropriate imaging modalities. Purpose: The purpose of this article is to review the available literature on the epidemiology, clinical manifestations and management of patients with sarcoidosis Materials and method: The available literature in PubMed was reviewed to write the article, using the keywords ,,sarcoidosis”, ,,cardiac sarcoidosis”, ,,pulmonary sarcoidosis” and ,,cutaneous sarcoidosis”. Conclusion: Sarcoidosis is associated with a significant increase in patient mortality, as well as decreased quality of life and physical disability. Efforts to accurately predict disease progression allow for more comprehensive and personalized patient care. As a life threatening disease, sarcoidosis needs to be diagnosed early and treated appropriately.

Mechanism matters: mortality and endothelial cell damage marker differences between blunt and penetrating traumatic injuries across three prehospital clinical trials.

Injury mechanism is an important consideration when conducting clinical trials in trauma. Mechanisms of injury may be associated with differences in mortality risk and immune response to injury, impacting the potential success of the trial. We sought to characterize clinical and endothelial cell damage marker differences across blunt and penetrating injured patients enrolled in three large, prehospital randomized trials which focused on hemorrhagic shock. In this secondary analysis, patients with systolic blood pressure < 70 or systolic blood pressure < 90 and heart rate > 108 were included. In addition, patients with both blunt and penetrating injuries were excluded. The primary outcome was 30-day mortality. Mortality was characterized using Kaplan-Meier and Cox proportional-hazards models. Generalized linear models were used to compare biomarkers. Chi squared tests and Wilcoxon rank-sum were used to compare secondary outcomes. We characterized data of 696 enrolled patients that met all secondary analysis inclusion criteria. Blunt injured patients had significantly greater 24-h (18.6% vs. 10.7%, log rank p = 0.048) and 30-day mortality rates (29.7% vs. 14.0%, log rank p = 0.001) relative to penetrating injured patients with a different time course. After adjusting for confounders, blunt mechanism of injury was independently predictive of mortality at 30-days (HR 1.84, 95% CI 1.06-3.20, p = 0.029), but not 24-h (HR 1.65, 95% CI 0.86-3.18, p = 0.133). Elevated admission levels of endothelial cell damage markers, VEGF, syndecan-1, TM, S100A10, suPAR and HcDNA were associated with blunt mechanism of injury. Although there was no difference in multiple organ failure (MOF) rates across injury mechanism (48.4% vs. 42.98%, p = 0.275), blunt injured patients had higher Denver MOF score (p < 0.01). The significant increase in 30-day mortality and endothelial cell damage markers in blunt injury relative to penetrating injured patients highlights the importance of considering mechanism of injury within the inclusion and exclusion criteria of future clinical trials.

Incidence and Outcomes of New-Onset Right Bundle Branch Block Following Transcatheter Aortic Valve Replacement.

The incidence and prognosis of right bundle branch block (RBBB) following transcatheter aortic valve replacement (TAVR) are unknown. Hence, we sought to characterize the incidence of post-TAVR RBBB and determine associated risks of permanent pacemaker (PPM) implantation and mortality. All patients 18 years and above without preexisting RBBB or PPM who underwent TAVR at US Mayo Clinic sites and Mayo Clinic Health Systems from June 2010 to May 2021 were evaluated. Post-TAVR RBBB was defined as new-onset RBBB in the postimplantation period. The risks of PPM implantation (within 90 days) and mortality following TAVR were compared for patients with and without post-TAVR RBBB using Kaplan-Meier analysis and Cox proportional hazards modeling. The risks of PPM implantation (within 90 days) and mortality following TAVR were compared for patients with and without post-TAVR RBBB using Kaplan-Meier analysis and Cox proportional hazards modeling. Of 1992 patients, 15 (0.75%) experienced new RBBB post-TAVR. There was a higher degree of valve oversizing among patients with new RBBB post-TAVR versus those without (17.9% versus 10.0%; P=0.034). Ten patients (66.7%) with post-TAVR RBBB experienced high-grade atrioventricular block and underwent PPM implantation (median 1 day; Q1, 0.2 and Q3, 4), compared with 268/1977 (13.6%) without RBBB. Following propensity score adjustment for covariates (age, sex, balloon-expandable valve, annulus diameter, and valve oversizing), post-TAVR RBBB was significantly associated with PPM implantation (hazard ratio, 8.36 [95% CI, 4.19-16.7]; P<0.001). No statistically significant increase in mortality was seen with post-TAVR RBBB (hazard ratio, 0.83 [95% CI, 0.33-2.11]; P=0.69), adjusting for age and sex. Although infrequent, post-TAVR RBBB was associated with elevated PPM implantation risk. The mechanisms for its development and its clinical prognosis require further study.

The Impact of Climate Change and Extreme Weather Conditions on Cardiovascular Health and Acute Cardiovascular Diseases

Climate change is widely recognized as one of the most significant challenges facing our planet and human civilization. Human activities such as the burning of fossil fuels, deforestation, and industrial processes release greenhouse gases into the atmosphere, leading to a warming of the Earth’s climate. The relationship between climate change and cardiovascular (CV) health, mediated by air pollution and increased ambient temperatures, is complex and very heterogeneous. The main mechanisms underlying the pathogenesis of CV disease at extreme temperatures involve several regulatory pathways, including temperature-sympathetic reactivity, the cold-activated renin-angiotensin system, dehydration, extreme temperature-induced electrolyte imbalances, and heat stroke-induced systemic inflammatory responses. The interplay of these mechanisms may vary based on individual factors, environmental conditions, and an overall health background. The net outcome is a significant increase in CV mortality and a higher incidence of hypertension, type II diabetes mellitus, acute myocardial infarction (AMI), heart failure, and cardiac arrhythmias. Patients with pre-existing CV disorders may be more vulnerable to the effects of global warming and extreme temperatures. There is an urgent need for a comprehensive intervention that spans from the individual level to a systemic or global approach to effectively address this existential problem. Future programs aimed at reducing CV and environmental burdens should require cross-disciplinary collaboration involving physicians, researchers, public health workers, political scientists, legislators, and national leaders to mitigate the effects of climate change.

P907 Impact of preoperative use of biologics on 30-day surgical morbidity and mortality in patients with Crohn’s Disease undergoing ileocolectomy: National Surgical Quality Improvement Program database analysis

Abstract Background Preoperative use of biologics has been inconsistently reported to be associated with increased frequency of infectious and surgical anastomotic complications in inflammatory bowel disease patients. We aimed to evaluate the rates of 30-day post operative morbidity and mortality in Crohn’s disease patients exposed preoperatively to biologics. Methods Data was collected from the NSQIP (National Surgical Quality Improvement Program) which is a nationally validated, risk adjusted program designed to measure and improve the quality of surgical care. Crohn’s disease patients undergoing open or laparoscopic ileocolectomy were identified using corresponding ICD 10 and CPT Codes from NSQIP PUF (Participant Use Data File) for the year 2021.Patients were divided based on the preoperative use of biologics (group 1) and (group 2) for whom no biologics were used. Univariate analysis was done on SPSS via Chi-squared and Fisher exact test for categorical variables, while independent sample T-test was used for continuous variables. Composite morbidity was defined as the association of any two morbidity events in the database. A multivariate regression analysis was done to predict post operative morbidity while controlling for the following variables: age, BMI, smoking, steroid use, diabetes, hypertension, sepsis, ASA classification, and preoperative transfusion. Results A total of 910 patients (female n=473; 52%, mean age of 42.3 ± 16.1) were included. The group1 patients were significantly younger (40.30 years ±15.33) than group 2 (43.58 years ±16.8 p=0.002) and had significantly slightly higher ASA III and IV scores (97.4% vs 97.2%, p=0.004). On the other hand, group 2 had a significantly higher prevalence of hypertension (20.2% vs 12.8%, p=0.003) and chronic obstructive pulmonary disease (2.6% vs 0, p=0.001). No significant difference in remaining preoperative variables, surgical approach (laparoscopic vs open) and comorbidities were found between the two groups. On univariate analysis of morbidity, only a significant prevalence of deep vein thrombosis and thromboembolism was found in patients exposed to biologics (1.1% vs 0 p=0.027). No significant difference was found in surgical site infections, sepsis, infectious complications, anastomotic failure, composite morbidity, or mortality. On multivariate analysis, no significant morbidity was noted between the two groups. Conclusion Crohn’s disease patients undergoing ileocolectomy and exposed preoperatively to biologics did not show a significant increase in 30-day postoperative morbidity and mortality.

The accumulation of modular serine protease mediated by a novel circRNA sponging miRNA increases Aedes aegypti immunity to fungus

BackgroundMosquitoes transmit many infectious diseases that affect human health. The fungus Beauveria bassiana is a biological pesticide that is pathogenic to mosquitoes but harmless to the environment.ResultsWe found a microRNA (miRNA) that can modulate the antifungal immunity of Aedes aegypti by inhibiting its cognate serine protease. Fungal infection can induce the expression of modular serine protease (ModSP), and ModSP knockdown mosquitoes were more sensitive to B. bassiana infection. The novel miRNA-novel-53 is linked to antifungal immune response and was greatly diminished in infected mosquitoes. The miRNA-novel-53 could bind to the coding sequences of ModSP and impede its expression. Double fluorescence in situ hybridization (FISH) showed that this inhibition occurred in the cytoplasm. The amount of miRNA-novel-53 increased after miRNA agomir injection. This resulted in a significant decrease in ModSP transcript and a significant increase in mortality after fungal infection. An opposite effect was produced after antagomir injection. The miRNA-novel-53 was also knocked out using CRISPR-Cas9, which increased mosquito resistance to the fungus B. bassiana. Moreover, mosquito novel-circ-930 can affect ModSP mRNA by interacting with miRNA-novel-53 during transfection with siRNA or overexpression plasmid.ConclusionsNovel-circ-930 affects the expression level of ModSP by a novel-circ-930/miRNA-novel-53/ModSP mechanism to modulate antifungal immunity, revealing new information on innate immunity in insects.

Ambulatory arterial stiffness index, mortality, and adverse cardiovascular outcomes; Systematic review and meta-analysis.

The ambulatory arterial stiffness index (AASI) is a novel measure of both blood pressure (BP) variability and arterial stiffness. This systematic review and meta-analysis was designed to evaluate the strength of the association between AASI and mortality and major adverse cardiovascular events (MACE). PubMed, Scopus, CINAHL, Google Scholar. and the Cochrane library were searched for relevant studies to July 31, 2023. Two investigators independently extracted data. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of all included articles. The relationship between baseline AASI and outcomes were examined using relative risk (RR) ratios with 95% confidence intervals (CI) with RevMan web. Thirteen studies were included and representing 28 855 adult patients who were followed up from 2.2 to 15.2 years. A 1-standard deviation (1-SD) increase in AASI was associated with a significant increase in all-cause death (RR 1.12; 95% CI: 0.95-1.32), stroke (RR 1.25; 95% CI: 1.09-1.44), and MACE (RR 1.07; 95% CI: 1.01-1.13; [I2 =32%]). Higher dichotomized AASI (above vs. below researcher defined cut-offs) was associated with a significant increase in all-cause mortality (RR 1.19; 95% CI: 1.06-1.32), cardiovascular death (RR 1.29; 95% CI: 1.14-1.46), stroke (RR 1.57; 95% CI: 1.33-1.85), and MACE (RR1.29; 95% CI: 1.16-1.44). There was a significant risk of bias in more than 50% of studies with no evidence of significant publication bias. Higher AASI is associated with an increased risk of all-cause and cardiovascular death, stroke, and MACE. Further high-quality studies are warranted to determine reproducible AASI cut-offs to enhance its clinical risk precision.

Diabetes mortality: trends and multi-country analysis of the Americas from 2000 to 2019.

Diabetes has been increasing worldwide and is now among the 10 leading causes of death globally. Diabetic kidney disease (DKD), a complication of poorly managed diabetes, is related to high mortality risk. To better understand the situation in the Americas region, we evaluated diabetes and DKD mortality trends over the past 20 years. We analysed diabetes and DKD mortality for 33 countries in the Americas from 2000 to 2019. Data were extracted from the World Health Organization (WHO) Global Health Estimates and the World Population Prospects, 2019 Revision, estimating annual age-standardized mortality rates (ASMR) and gaps in the distribution of diabetes and DKD mortality by sex and country. Trend analyses were based on the annual average percentage of change (AAPC). From 2000 to 2019, the overall mortality trend from diabetes in the Americas remained stable [AAPC: -0.2% (95% CI: -0.4%-0.0%]; however, it showed important differences by sex and by country over time. By contrast, DKD mortality increased 1.5% (1.3%-1.6%) per year, rising faster in men than women, with differences between countries. Central America, Mexico and the Latin Caribbean showed significant increases in mortality for both diseases, especially DKD. In contrast in North America, diabetes mortality decreased whereas DKD mortality increased. The increase in DKD mortality is evidence of poorly controlled diabetes in the region. The lack of programmes on prevention of complications, self-care management and gaps in quality health care may explain this trend and highlight the urgent need to build more robust health systems based on primary care, prioritizing diabetes prevention and control.

Effect of Asymptomatic Common Carotid Artery Dissection on the Prognosis of Patients With Acute Type A Aortic Dissection.

Acute type A aortic dissection can extend upwards to involve the common carotid artery. However, whether asymptomatic common carotid artery dissection (CCAD) requires surgical repair remains controversial. This study aimed to explore the effect of asymptomatic CCAD without surgical intervention on the prognosis of patients who underwent surgery for acute type A aortic dissection. Between January 2015 and December 2017, 485 patients with no neurological symptoms who underwent surgery for acute type A aortic dissection were enrolled in this retrospective cohort study. The patients were divided into 2 groups based on the exposure factor of CCAD. CCAD was detected in 111 patients (22.9%), and after adjusting baseline data (standardized mean difference <0.1), the 30-day mortality (17.1% versus 6.0%, P<0.001) and incidence of fatal stroke (7.7% versus 1.6%, P=0.001) were significantly higher in the group with CCAD. Univariable and multivariable Cox regression analyses found CCAD as an independent risk factor for 30-day mortality (hazard ratio [HR], 2.8 [95% CI, 1.5-5.2]; P=0.001). At a median follow-up of 6.2 years (interquartile range, 5.6-6.9 years), landmark analysis with a cutoff value of 1 month postoperatively showed a significant increase in mortality in the group with CCAD, especially in the first month (log-rank P=0.002) and no significant difference in survival after the first month postoperatively between the 2 groups (log-rank P=0.955). Asymptomatic CCAD increased the risk of early fatal stroke and death in patients with acute type A aortic dissection after surgery but did not affect midterm survival in patients who survived the early postoperative period.

Remote Surgical Discussion of Multivessel Coronary Artery Disease Patients without Surgery on Site-Retrospective Insights.

The heart team approach is highly advocated for in treatment decision making in patients with multivessel disease (MVD). Nevertheless, many centers lack on-site cardiac surgical services (CSS)/formal heart team. Our local alternative is of remote surgical consultation without a structured image sharing platform. In our understanding, the incidence of anatomical complete revascularization (ACR) under this daily practice, and its clinical impact, has not been discussed before. We analyzed 477 consecutive patients who were surgically revascularized between January 2009 and March 2018 for MVD, after remote surgical consultation. Unstable, late arrival, and ST elevation patients were excluded (n = 163). ACR was considered grafting all anatomic lesions > 50%. Syntax score (SS) calculation and ACR categorization were determined by an independent interventionalist using diagnostic angiograms and available operative reports (n = 267). Patients' outcomes were assessed in relation to multiple clinical variables including troponin result and the revascularization status. Three hundred and fourteen patients were included. Mean age was 64 years, and mean SS-II was 27.3 ± 11. At the 4-year follow-up, the observed mortality (11.8% and 12.9%, with troponin-positive and -negative groups, respectively), myocardial infarction (11.8%), and repeat revascularization (9.8%) were higher than those predicted using a nomogram depicting the predicted 4-year mortality as a function of the SYNTAX II Score (5.3%, 8.8%, and 3.5%, respectively, p = 0.02). ACR was reported in 33% of 267 available patients' reports. After multivariate adjustment ACR was the only variable associated with a significant increase in 4-year mortality (12.3% vs. 6.7%, p < 0.05). Partial revascularization in the absence of on-site CSS and a structured heart team platform is a frequent occurrence. Not surprisingly, this occurrence was associated with a higher risk for mid-term mortality. An upfront, structured, virtual, heart team interface is mandatory to particularly prioritize the completeness of revascularization when considering the optimal revascularization mode.

Features of infective endocarditis in a contemporary cohort of persons who inject drugs: a matched comparison analysis of long-term prognostic factors.

The objective of the study was to assess the short- and long-term mortality of infective endocarditis (IE) among people who inject drugs (PWID). Using prospectively collected data on hospitalized patients (years 2000 through 2021) with IE, PWID were identified and included in this study. Survival analysis was performed to analyze short- and long-term mortality and study their risk factors among PWID and a matched group of non-intravenous drug users (N-IDU). In a study of 485 patients admitted for IE, 55 (11%) of them were PWID. These PWID patients were 1:1 age- and sex- matched to an N-IDU group (N = 55 per group). Both groups had similar baseline comorbid conditions, including congestive heart failure, type 2 diabetes, and neoplastic diseases. However, PWID were more likely to have HCV co-infection (62% vs 16%, respectively, p < 0.001) and advanced liver disease/cirrhosis (52% vs 7.9%, respectively, p < 0.001). IE in PWID more often affected the tricuspid valve (42% vs 22%, respectively, p = 0.024) and presented with more embolic events (66% vs 35%, respectively, p < 0.01). S. aureus was the primary cause of IE in PWID (44% vs 21%, respectively, p = 0.01). After adjusting for other variables, PWID (HR = 2.99, 95% CI [1.06, 8.43], p = 0.038) and valve bioprosthetic replacement (HR = 5.37, 95% CI [1.3, 22.1], p = 0.02) were independently associated with increased mortality risk, whereas IE caused by tricuspid valve infection was associated with reduced mortality risk (HR = 0.25, 95% CI [0.06, 0.97], p = 0.046). In this cohort, PWID had increased risk of long-term mortality after hospital discharge for IE, when compared to matched N-IDU with similar baseline characteristics. The reasons behind the significant increase in mortality warrant further investigation.

Maintaining a Whole Blood-Centered Transfusion Improves Survival in Hemorrhagic Resuscitation.

Whole blood (WB) transfusion has been shown to improve mortality in trauma resuscitation. The optimal ratio of packed red blood cells (pRBC) to WB in emergent transfusion has not been determined. We hypothesized that a low pRBC:WB transfusion ratio is associated with improved survival in trauma patients. We analyzed the 2021 Trauma Quality Improvement Program (TQIP) database to identify patients who underwent emergent surgery for hemorrhage control and were transfused within four hours of hospital arrival, excluding transfers or deaths in the emergency department. We stratified patients based on pRBC:WB ratios. The primary outcome was mortality at 24 hours. Logistic regression was performed to estimate odds of mortality among ratio groups compared to WB alone, adjusting for injury severity, time to intervention, and demographics. Our cohort included 17,562 patients; of those, 13,678 patients had only pRBC transfused and were excluded. FFP:pRBC ratio was balanced in all groups. Among those who received WB (n = 3,884), there was a significant increase in 24-hour mortality with higher pRBC:WB ratios (WB alone 5.2%, 1:1 10.9%, 2:1 11.8%, 3:1 14.9%, 4:1 20.9%, 5:1 34.1%, p = 0.0001). Using empirical cutpoint estimation we identified a 3:1 ratio or less as an optimal cutoff point. Adjusted odds ratios of 24-hour mortality for 4:1 and 5:1 groups were 2.85 (95% CI: 1.19 - 6.81) and 2.89 (95% CI: 1.29 - 6.49), respectively. Adjusted hazard ratios of 24-hour mortality were 2.83(95%CI: 1.18 - 6.77) for 3:1 ratio, 3.67(95%CI: 1.57 - 8.57) for 4:1 ratio, and 1.97(95%CI: 0.91 - 4.23) for 5:1 ratio. Our analysis shows that higher pRBC:WB ratios at 4 hours diminished survival benefits of WB in trauma resuscitation. Further efforts should emphasize this relationship to optimize trauma resuscitation protocols.

The dose–response effect of time between emergency admission and inpatient care on mortality

To analyse mortality associated to emergency admissions on weekends, differentiating whether the patients were admitted to the Internal Medicine department or to the hospital as a whole. Retrospective follow-up study of patients discharged between 2015 and 2019 in: (a) the Internal Medicine department (n = 7656) and (b) the hospital as a whole (n = 83,146). Logistic regression models were fitted to analyse the risk of death, adjusting for age, sex, severity, Charlson index, sepsis, pneumonia, heart failure and day of admission. Cox models were also adjusted for the time from admission until normal inpatient care. There was a significant increase in mortality for patients admitted in weekends with short stays in Internal Medicine (48, 72 and 96 h: OR = 2.50, 1.89 and 1.62, respectively), and hospital-wide (OR = 2.02, 1.41 and 1.13, respectively). The highest risk in weekends occurred on Fridays (stays ≤ 48 h: OR = 3.92 [95% CI 2.06–7.48]), being no significative on Sundays. The risk increased with the time elapsed from admission until the inpatient department took over care (OR = 5.51 [95% CI 1.42–21.40] when this time reached 4 days). In Cox models patients reached HR = 2.74 (1.00–7.54) when the delay was 4 days. Whether it was Internal Medicine or hospital-wide patients, the risk of death associated with emergency admission in WE increased with the time between admission and transfer of care to the inpatient department; consequently, Friday was the day with the highest risk while Sunday lacked a weekend effect. Healthcare systems should correct this serious problem.

Abstract C052: Effect of ginger extracts on hepatocellular carcinoma cell lines-derived from Caucasian, Asian, and African American patients

Abstract Hepatocellular Carcinoma (HCC) is a highly fatal disease with mortality running parallel to its incidence. For HCC, race/ethnicity plays a vital role in determining incidence, mortality, and survival rates. The incidence of HCC is highest in Asia and Africa. Furthermore, there is a statistically significant increase in incidence and mortality and a decrease in 5-year survival rates in African American (AA)/Black patients compared to non-Hispanic white patients. There is a knowledge gap in our understanding of the molecular mechanism underlying the HCC racial disparity between AA/Black, White, and Asian patients. To understand the underlying cause, we performed bioinformatics on existing gene expression data. We found that type I Interferon (IFN-I) signaling pathway showed statistically significant activation in AA/Black patients compared to white patients. Over 60% of Gen Xers/Millennials are taking a more holistic approach to their diet to prevent chronic diseases, including cancer. We hypothesized that dietary compounds exert anticancer effects on HCC, and because of their anti-inflammatory property, they might modulate the IFN-I signaling pathway. We tested ginger extracts on HCC derived from white (HepG2), Black (Hep3B and O/20), and Asian (Hu7) cancer patients. A dose-response of these extracts was used to determine IC50s on these cell lines using an MTT cell proliferation assay. Activation of INF-1-mediated downstream signaling proteins, including JAK1, TYK2, STAT1, and STAT2 phosphorylation status, was determined on a Western blot analysis using phospho-specific primary antibodies. The expression of Interferon Signaling Genes (ISGs), including Myxovirus resistance gene 1 (MX1), 2′,5′-oligoadenylate synthetase (OAS1), Interferon-alpha inducible protein 6 (IFI6), and Interferon stimulated gene 15 (ISG15) was assayed using a quantitative Real-Time Polymerase Chain Reaction (RT-PCR). Ginger has a significantly (P&amp;lt;0.05) lower IC50s (mg/ml) on cell lines from Black patients (Hep3B=156 ± 3, and O/20=162 ± 3) than cell lines from white (HepG2=176±5) or Asian (Hu7=174 ± 5) patients. Our data show that untreated cells exhibited phosphorylation/activation of IFN-1 downstream mediators, including JAK1, TYK2, STAT1, and STAT2 proteins. Ginger treatment reduced the phosphorylation of these IFN downstream mediators in all HCC cell lines. Furthermore, expression of MX1, ISG15, IF16, and OAS1 was also reduced in all HCC cells lines in a dose-dependent manner; however, the effects on gene expression were more sensitive to a lower concentration of ginger extract in Black patients derived HCC cell lines than other HCC cell lines. Currently, research is underway to identify the active chemical agent in ginger and test it on other patient-derived HCC lines and in an in vivo model. In conclusion, our data suggest that ginger can potentially attenuate IFN-mediated signaling pathways in HCC, and cells from Black HCC patients may be more sensitive to ginger (Funded: P20 CA264068-01). Citation Format: Sadia Kanwal, Eva Davis, Seung Lee, Milton Omar Faison, Devanand Sarkar, Rafat Ali Siddiqui. Effect of ginger extracts on hepatocellular carcinoma cell lines-derived from Caucasian, Asian, and African American patients [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 C052.

Changing Trends in Sickle Cell Disease-Related Mortality in the United States over Four Decades

Introduction: Sickle cell disease (SCD) causes significant morbidity and early mortality. The Cooperative Study of Sickle Cell Disease estimated median life expectancy for individuals with SCD at 42 years for males and 48 years for females in the early 1990s. However, this calculation was made prior to now standards-of-care in SCD, including routine transcranial doppler screening, pneumococcal prophylaxis, and the introduction of the primary disease-modifying therapy hydroxyurea and the widespread use of chronic blood transfusion. Over the last thirty years, with expanded access to disease modifying therapies, increased evidence exists for the preservation of organ function and less frequent acute vaso-occlusive pain. It remains unclear whether the introduction of these therapies has affected overall SCD-related mortality or the specific causes of death of those with SCD in the United States, particularly in the last decade when the use of hydroxyurea has expanded most significantly. Methods: We used the US mortality statistics for 1979-2020 available publicly through the CDC WONDER database (http://wonder.cdc.gov), which is a compilation of county, state, and national-level mortality statistics derived from death certificates, including age category at death, sex, race, ethnicity, year of death, underlying cause of death, and additional contributing causes using ICD-9 codes for 1979-1998 (282.6 sickle cell anemia- all SCD genotypes were included under one code in ICD-9) and ICD-10 codes for 1999-2020 (D57.0 sickle cell anemia with crisis; D57.1 sickle cell anemia without crisis; D57.2 double heterozygous sickling disorders; D57.8 other sickle cell disorders). We searched the SCD ICD-10 codes listed as underlying cause of death by five-year age groups for Black individuals and all ethnicities, (from Hamideh and Alvarez, Pediatric Blood and Cancer 2013) and compared the crude death rates overall and for each age group to those of 1999-2009. We also searched using the SCD ICD-10 codes included in “the multiple causes of death” to determine the 15 most common ICD categories of death in each 10-year period. Results: For the period 2010-2020, 5272 Black (Hispanic &amp; non-Hispanic) individuals died in the United States with the underlying cause of death listed as one of the ICD-10 SCD codes (see Figure 1A for a map of the crude mortality rate distribution). The crude mortality rate was 1.1 per 100,000 Black individuals, which was significantly lower than the period 1999-2009 (crude rate 1.2 per 100,000, p &amp;lt; 0.0001) (Figure 1B). Of note, similar to prior trends, there is a significant increase in mortality rate in the 15-19 year age group versus 20-24 years (0.9 per 100,000 to 1.4 per 100,000, p &amp;lt; 0.0001) corresponding with the age of transition to adult centers. The mean age at death for all genotypes for 2010-2020 was 43 years (females: 44 years, males: 41 years) versus 39 years for 1999-2009 (females: 40 years, males: 38 years). For the period 2010-2020, 61% of cases listed SCD as the primary cause of death without specificity or proximal cause; for the other 39% of cases when an underlying cause of death was noted, cardiovascular disease was the most common (28%), followed by accidents (7%), cerebrovascular disease (7%), malignancy (6%), septicemia (4.8%), and renal disease (3.8%). The fifteen most common causes of death accounted for 90% of underlying causes of death listed in the SCD population. Conclusion: The sickle cell disease-related mortality rate has significantly declined over the last 40 years, including in the period 1999-2020, corresponding with the introduction of disease modifying therapies, improved SCD care, and decreased infant mortality. This overall improvement, however, provides contrast to the enduring sharp increase in mortality in the young adult years. This demonstrates the critical need to improve the transition process from pediatric to adult care and to emphasize the need for additional support for young adults after they transition to adult SCD care.

Cardiovascular (CV) Mortality Among Adults Diagnosed with Leukemias: A Retrospective Cohort Study

Background CV mortality has been recognized as the preventable cause of death in most cancers. However, there is a scarcity of data exploring CV mortality in adults diagnosed with leukemia. Hence, understanding the timing, and quantifying the magnitude of CV mortality can facilitate strategies to reduce the burden of mortality in these patients. Methods Surveillance, Epidemiology, and End Results (SEER) database (2004-2018) was queried to obtain CV mortality (defined as deaths due to heart diseases, hypertension, cerebrovascular diseases, atherosclerosis, and aortic aneurysm and dissection) in adults (&amp;gt;18 years of age) diagnosed with leukemias including acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Standardized mortality ratios (SMRs) were calculated. SMR was defined as the observed deaths from each category divided by the expected number of deaths in the age-matched US population for the same period. SMR &amp;gt;1 indicated increased while &amp;lt;1 indicated decreased mortality. SMR was presented by latency periods of &amp;lt;2, 2-5, and &amp;gt;5 years after the initial diagnosis of leukemias and stratified by age (&amp;lt;50 years, 50-70 years, &amp;gt;70 years), race (White, Black, Asian/Pacific Islander, Native American), ethnicity (Hispanic, Non-Hispanic), and marital status (married vs single/divorced/widowed). Results This analysis included 120,193 leukemia patients. Of which, 61,763 had lymphocytic leukemia and 58,430 were diagnosed with myeloid leukemia. In overall population, a significant increase in mortality was observed in adults diagnosed with leukemia (SMR: 1.34, 95% CI: 1.27-1.40). The risk of CV death was highest &amp;lt;2 years of initial diagnosis (1.94, 1.87-2.01) as compared to the population who died 2-5 years (1.17, 1.11-1.23) and &amp;gt;5 years (1.07, 1.01-1.14) after the initial diagnosis. In terms of different subgroups, patients aged &amp;lt;50 years observed the highest risk of CV mortality within &amp;lt; 2 years (9.35, 6.54-13.38) compared to patients aged 50-70 years (2.73, 2.45-3.04), and aged &amp;gt;70 years (1.80, 1.73-1.88). Similarly, regarding race, Asians/Pacific islanders had the highest risk of CV mortality (4.41, 3.70-5.26) followed by Blacks (2.58, 2.26-2.94), and Whites (1.85, 1.78-1.92) within &amp;lt;2 years of initial diagnosis. There was a significant increase in observed mortality in Hispanic (2.83, 2.47-3.23) as well as in non-Hispanic (1.90, 1.83-1.97) population within &amp;lt;2 years of initial diagnosis. However, the magnitude was relatively higher in Hispanic as compared to non-Hispanics. The risk of CV death was observed to be higher in single/divorced/widowed patients (2.30, 2.00-2.20) compared to those who were married (1.81, 1.71-1.91). The CV mortality risk remained consistent for all subtypes of leukemias (ALL, CLL, AML and CML) in overall patient population and among subgroups of interest over different latency periods of &amp;lt;2, 2-5, and &amp;gt; 5years after the initial diagnosis. Small sample size in Native Americans precluded any meaningful statistics. Conclusions: Risk of CV mortality among adults with leukemia is observed to be highest among younger (&amp;lt;50 years), Asians, Hispanics, and single/divorced/widowed patients, especially within 2 years of initial diagnosis. A risk-adapted approach may be warranted for cardiovascular care in these patients. Targeted cardio-oncological strategies should be aimed at improving CV mortality in patients who are at the highest risk of death.

Resource allocation during the coronavirus disease 2019 pandemic and the impact on patients with lung cancer: a systematic review.

The coronavirus disease 2019 (COVID-19) pandemic resulted in unprecedented tolls on both economies and human life. Healthcare resources needed to be reallocated away from the care of patients and towards supporting the pandemic response. In this systematic review, we explore the impact of resource allocation during the COVID-19 pandemic on the screening, diagnosis, management and outcomes of patients with lung cancer during the pandemic. PubMed and Embase were systematically searched for articles investigating the impact of the COVID-19 pandemic on patients with lung cancer. Of the 1605 manuscripts originally screened, 47 studies met the inclusion criteria. Patients with lung cancer during the pandemic experienced reduced rates of screening, diagnostic testing and interventions but did not experience worse outcomes. Population-based modelling studies predict significant increases in mortality for patients with lung cancer in the years to come. Reduced access to resources during the pandemic resulted in reduced rates of screening, diagnosis and treatment for patients with lung cancer. While significant differences in outcomes were not identified in the short term, ultimately the effects of the pandemic and reductions in cancer screening will likely be better delineated in the coming years. Future consideration of the long-term implications of resource allocation away from patients with lung cancer with an attempt to provide equitable access to healthcare and limited interruptions of patient care may help to provide the best care for all patients during times of limited resources.

Sars-Cov-2 and Chronic Myeloid Leukemia: A Systematic Review

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing the coronavirus disease of 2019. Numerous mutations had developed in SARS-CoV-2 virus that resulted in strains (Alfa Beta Delta Omicron) with varying degrees of virulence disease severity. In coronavirus disease of 2019 (COVID-19) patients with chronic myeloid leukemia (CML), there is a controversy regarding the effect of tyrosine kinase inhibitors (TKI) on SARS-CoV-2 infection and patients' outcomes. Some studies showed that CML patients with COVID-19 had better outcomes; other reports showed no significant difference. Method Following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, PubMed, Scopus, and Google Scholar databases were searched for published articles through 20 April 2023 for qualified studies. The search included retrospective, prospective studies, reviews, case series, and case reports. The inclusion criteria were English literature with CML patients above 18 years who had SARS-CoV-2 infection. Articles in languages other than English and articles with non-sufficient information were excluded, and patients with bone marrow transplants were excluded. Search terms were (chronic myeloid leukemia) OR (chronic myelogenous leukemia) AND (SARS-CoV-2) OR (COVID-19). Two eligibility checks were done on the included studies. Title and abstract screening was completed first, and the full text of articles that met the requirements for inclusion was subsequently obtained. The search included all articles published up to 20 April 2023. The review is registered in PROSPERO (registration number is: CRD42022326674). Results We reviewed 36 articles of published literature up to April 2023 and collected data for a total of 686 CML patients with COVID-19. The vast majority of patients were in the chronic phase; seven patients were in the accelerated phase, and eight patients were in the blast phase. Disease severity was classified according to WHO criteria. Twenty-seven patients were managed at home, and 21 patients were in ICU (intensive care unit) during the hospital course. Twenty-six patients required oxygen therapy; among them, seven patients required intubation and mechanical ventilation, and six patients required non-invasive ventilation. Mortality was seen in 47 patients, and there were no reports of thrombotic events, but some patients developed AKI, autoimmune hemolytic anemia, rhabdomyolysis, and DKA during COVID-19. Limitations The major limitation is the lack of details about the use or hold of TKIs during SARS-CoV-2 infection in the majority of the reports. Also, the specific or predominant strain of SARS-CoV-2 was not mentioned. Few studies mentioned the variant of the virus, which make it difficult to compare the outcome of the different variant of the SARS-CoV-2 virus in patients with CML. Discussion/Conclusions Hematological cancers are associated with an increased risk of thrombosis. Thrombosis risk is expected to increase in patients with COVID-19; interestingly, patients with CML have not been reported to have a significant increase in the risk of thrombosis during COVID-19. The crucial point is, does TKI continuation during COVID-19 beneficial or harmful? Few patients continued TKIs during Covid-19 without serious adverse events. For patients who had the TKI continued, there were no mortality or serious adverse events. In vitro, TKIs were found to have a significant effect on inhibiting viral replication, which might be the reason behind the better outcome in CML patients infected with SARS-CoV-2 virus. On the other hand, there is a theoretical risk of increased severe infection in CML patients taking TKI due to targeted inhibition of kinases involved in immune cell function. This might result in suppressed cellular immune response that facilitates viral replication. Despite that, CML patients with COVID-19 have no significant increase in mortality or ICU admission compared to other hematological malignancies. in fact, our review showed that the mortality of CML patients with COVID-19 has significantly improved from 0.12% in the pre-vaccination period to 0.04% in the post-vaccination era. The available data indicates that, COVID-19's effect on patients with chronic myeloid leukemia (CML) still needs to be better understood due to the limited data.