Higher Risk Of Mortality Research Articles

Interleukin-6 and Interleukin-10 as a Predictor of Mortality in Elderly with COVID-19.

The age group at the most high risk for mortality due to SARS-CoV-2 infection was the elderly. This study aims to analyze markers that can predict the severity and mortality of elderly COVID-19 patients. This study used a cohort retrospective design. We include adult and elderly COVID-19 patients at Universitas Airlangga Hospital from March to August 2021. The sample used was 48 COVID-19 patients with positive real-time polymerase chain reaction swab results. We check the complete blood count and serum levels of interleukin-6 (IL-6) and IL-10 using enzyme-linked immunosorbent assay during admission. Data were analyzed using t -test, Mann-Whitney, Chi-square, Pearson, and Kendall Tau correlation. Leukocyte level (6.6 ± 2.5) was lowest in the severe-critical elderly group. Neutrophil level (75.3 ± 10.2) was highest in the mild-moderate elderly group. Lymphocyte level (18.8 ± 8.7) was highest in mild-moderate nonelderly group. Platelet level (279.0 ± 117.7) was highest in the mild-moderate elderly group. Neutrophil to lymphocyte ratio level (9.1 ± 9.4) was highest in the severe-critical nonelderly group, IL-6 level (98.6 ± 144.1) was highest in the severe-critical elderly group, IL-10 level (107.7 ± 47.7) was highest in the severe-critical elderly group and highest IL-6/IL-10 level (1.4 ± 1.7) was found in the mild-moderate elderly group no significant differences in biomarkers identification between the elderly and nonelderly groups. There was a substantial relationship between IL-10 levels and gender, IL-10 level, and hospital discharge condition. Female elderly patients and alive elderly patients were correlated with increased levels of IL-10.

Abatacept versus tumor necrosis factor inhibitors on mortality and medical utilizations in the treatment of rheumatoid arthritis associated interstitial lung disease: a large-scale real-world retrospective cohort study

Rheumatoid arthritis is a chronic inflammatory disease, and interstitial lung disease is one of the important extra-articular manifestations. There is limited evidence comparing abatacept (ABA) and tumor necrosis factor inhibitors (TNFi) regarding the risk of mortality among patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD). The aim of this study is to investigate the risk of mortality in patients with RA-ILD treated with ABA compared to TNFi. This retrospective cohort study utilized TriNetX electronic health record database. We enrolled patients who were diagnosed with RA-ILD and had received a new prescription for either ABA or TNFi. Patients were categorized into two cohorts based on their initial prescription. The primary outcome was all-cause mortality, and secondary outcomes were healthcare utilizations, including hospitalization, critical care services, and mechanical ventilation. Subgroup analyses were performed on age, presence of anti-citrullinated peptide antibodies (ACPA), and cardiovascular risk. Among 34,388 RA-ILD patients, 895 were selected for each group (ABA and TNFi) following propensity score matching. The ABA group exhibited a higher all-cause mortality risk. (HR 1.296, 95% CI 1.006–1.671). Subgroup analysis showed a heightened risk of receiving mechanical ventilation in ABA-treated patients aged 18–64 years old (HR 1.853, 95% CI 1.002–3.426), and those with cardiovascular risk factors (HR 2.015, 95% CI 1.118–3.630). Another subgroup analysis indicated a higher risk of mortality among ABA-treated patients with positive-ACPA. (HR 4.138 95% CI 1.343–12.75). This real-world data research demonstrated a higher risk of all-cause mortality in RA-ILD patients treated with ABA compared to TNFi, particularly those aged 18–64 years, lacking cardiovascular risk factors, and positive-ACPA. ABA was associated with an increased risk of mechanical ventilation in patients aged 18–64 years and those with cardiovascular risk factors.

Prognostic Impact of the Ratio of Hemoglobin to Red Blood Cell Distribution Width in Patients after Acute Decompensated Heart Failure.

Objective The ratio of hemoglobin to red blood cell distribution width (Hb/RDW) is a simple and readily available tool associated with adverse outcomes in chronic heart failure (HF). However, the association between the Hb/RDW ratio and mortality in patients with acute decompensated HF (ADHF) is unclear. The goal of this study was to investigate the relationship between the Hb/RDW ratio and mortality in patients after ADHF. Methods This single-center study included clinical and laboratory data collected at baseline, with patients prospectively followed-up for a median period of 3.1 years. The patients were divided into two groups based on their median Hb/RDW ratio. Patients We evaluated 250 consecutive patients hospitalized for ADHF at Shinshu University Hospital between July 2014 and March 2019. Results In our study cohort (median age, 76 [66-83] years; 62.8 % male), all-cause death was observed in 91 patients (incidence rate: 12.7 per 100 patient-years). A Kaplan-Meier analysis revealed that patients in the lower Hb/RDW ratio group (<0.24, n=131) had worse outcomes compared to those in the higher group (≥0.24, n=119) (cumulative incidence 44.1% vs. 19.5%, respectively; log-rank, P <0.001). After adjusting for demographics, HF severity, and laboratory biomarkers, a lower Hb/RDW ratio was significantly associated with a higher risk of mortality (hazard ratio, 1.89; 95% confidence interval, 1.04-3.45; P = 0.038). Conclusion A lower Hb/RDW ratio is associated with an increased risk of mortality in patients after ADHF, thus indicating its potential utility in identifying patients at an elevated risk for future cardiovascular events.

Pre-procedural nursing home length of stay and outcomes of transcatheter aortic valve replacement.

Older adults with severe aortic stenosis (AS) may receive care in a nursing home (NH) prior to undergoing transcatheter aortic valve replacement (TAVR). NH level of care can be used to stabilize medical conditions, to provide rehabilitation services, or for long-term care services. Our primary objective is to determine whether NH utilization pre-TAVR can be used to stratify patients at risk for higher mortality and poor disposition outcomes at 30 and 365 days post-TAVR. We conducted a retrospective cohort study among Medicare beneficiaries who spent ≥1 day in an NH 6 months before TAVR (2011-2019). The intensity of NH utilization was categorized as low users (1-30 days), medium users (31-89 days), long-stay NH residents (≥ 100 days, with no more than a 10-day gap in care), and high post-acute rehabilitation patients (≥90 days, with more than a 10-day gap in care). The probabilities of death and disposition were estimated using multinomial logistic regression, adjusting for age, sex, and race. Among 15,581 patients, 9908 (63.6%) were low users, 4312 (27.7%) were medium users, 663 (4.3%) were high post-acute care rehab users, and 698 (4.4%) were long-stay NH residents before TAVR. High post-acute care rehabilitation patients were more likely to have dementia, weight loss, falls, and extensive dependence of activities of daily living (ADLs) as compared with low NH users. Mortality was the greatest in high post-acute care rehab users: 5.5% at 30 days, and 36.4% at 365 days. In contrast, low NH users had similar mortality rates compared with long-stay NH residents: 4.8% versus 4.8% at 30 days, and 24.9% versus 27.0% at 365 days. Frequent bouts of post-acute rehabilitation before TAVR were associated with adverse outcomes, yet this metric may be helpful to determine which patients with severe AS could benefit from palliative and geriatric services.

High cardiovascular mortality risk among older merkel cell carcinoma patients

ObjectivePrevious research has primarily focused on the incidence and mortality rates of Merkel cell carcinoma (MCC), neglecting the examination of cardiovascular mortality (CVM) risk among survivors, particularly older patients. This study aims to assess the risk of CVM in older individuals diagnosed with MCC.MethodsData pertaining to older MCC patients were obtained from the Surveillance, Epidemiology, and End Results database (SEER). CVM risk was measured using standardized mortality ratio (SMR) and cumulative mortality. Multivariate Fine-Gray’s competing risk model was utilized to evaluate the risk factors contributing to CVM.ResultsAmong the study population of 2,899 MCC patients, 465 (16.0%) experienced CVM during the follow-up period. With the prolongation of the follow-up duration, the cumulative mortality rate for CVM reached 27.36%, indicating that cardiovascular disease (CVD) became the second most common cause of death. MCC patients exhibited a higher CVM risk compared to the general population (SMR: 1.69; 95% CI: 1.54–1.86, p < 0.05). Notably, the SMR for other diseases of arteries, arterioles, and capillaries displayed the most significant elevation (SMR: 2.69; 95% CI: 1.16–5.29, p < 0.05). Furthermore, age at diagnosis and disease stage were identified as primary risk factors for CVM, whereas undergoing chemotherapy or radiation demonstrated a protective effect.ConclusionThis study emphasizes the significance of CVM as a competing cause of death in older individuals with MCC. MCC patients face a heightened risk of CVM compared to the general population. It is crucial to prioritize cardiovascular health starting from the time of diagnosis and implement personalized CVD monitoring and supportive interventions for MCC patients at high risk. These measures are essential for enhancing survival outcomes.

Autonomic neuropathy in dialysis patients – investigations with a new symptom score (COMPASS 31)

BackgroundSymptoms of autonomic neuropathy (AN) are common in patients with diabetes and advanced renal disease. As yet different domains of autonomic neuropathy cannot be detected by a singular laboratory or invasive test. COMPASS 31, a new self-assessment test, has shown reliable results not only in cardiac autonomic neuropathy but also in different sub-domains when judging manifestation of AN by scores.MethodsOne hundred eighty-three patients with or without diabetes were enrolled, one hundred nineteen of them were treated with permanent dialysis therapy (HD), sixty-four patients served as controls (eGFR > 60 ml/min.) Using COMPASS 31 different symptoms of AN were assessed (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, pupillomotor changes) and transferred into AN-scores.ResultsAN was more pronounced in dialysis patients compared with controls (AN-score 27,5 vs. 10,0; p < 0,01). These differences were present also in every sub-domain of AN (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, pupillomotor changes; p < 0,05 for all sub-domains). In diabetic patients there was a strong correlation between symptoms of AN and diabetes duration (correlation coefficient r = 0,45, p < 0,001). Current glycemic control (HbA1c), body mass index (BMI), sex, and height had no influence on AN when comparing dialysis patients and controls. C-reactive protein (CRP) showed a positive linear correlation with AN-scores (correlation coefficient r = 0,21; p < 0,05).ConclusionSymptoms of AN are more pronounced in dialysis patients not only in total but also in all different domains of neuropathic changes. Longlasting diabetic disease promotes development of AN, as duration of diabetes was positively correlated with AN. Future longitudinal studies might help to identify the high cardiovascular and mortality risk in dialysis patients by the easy-to-use COMPASS 31 without need of invasive and time-spending methods for diagnosing AN.

Predictors of Mortality in Crimean-Congo Hemorrhagic Fever Patients Admitted at a Tertiary Care Hospital in Pakistan over the Last 10 Years: A Case-Control Study.

The objective was to identify predictors of mortality in hospitalized patients with Crimean-Congo hemorrhagic fever (CCHF). A case-control study was conducted on patients hospitalized with CCHF from 2012 to 2022. Risk factors for mortality in CCHF patients were analyzed using logistic regression. A total of 86 patients with a median age of 36 years (interquartile range [IQR], 27-36 years) were included, and the majority were males (78, 90.7%). Thirty-one patients (36%) were cases, whereas 55 (64%) were control patients. Based on univariate logistic regression analysis, patients who were in an age group of ≥40 years (odds ratio [OR]: 4.85; 95% CI: 1.8-12.4) or with presence of gum bleeding (OR: 2.66; 95% CI: 1.0-6.8), unit increase in white blood cell count (WBC) (OR: 1.09; 95% CI: 1.00-1.07), serum glutamate-pyruvate transaminase of ≥500 U/L (OR: 3.68; 95% CI: 1.4-9.3), serum glutamic-oxaloacetic transaminase (SGOT) of ≥1,000 U/L (OR: 8.72; 95% CI: 2.6-28.3), prothrombin time (PT) of ≥120 seconds (OR: 9.85; 95% CI: 3.2-29.8), international normalized ratio of ≥5 (OR: 15.8; 95% CI: 2.0-125.3), or acute respiratory distress syndrome (ARDS) (OR: 28.27; 95% CI: 5.84-136.9) were found to be significantly associated with mortality in CCHF. Factors found to be independently associated with mortality on multivariate analysis included ARDS (adjusted OR [aOR]: 27.7; 95% CI: 4.0-190.5), unit increase in WBC (aOR: 1.02; 95% CI: 1.02-1.26), SGOT of ≥1,000 U/L (aOR: 23.6; 95% CI: 2.32-241.7), and PT of ≥120 seconds (OR: 10.2; 95% CI: 2.00-52.4). CCHF is a rare but fatal disease, and patients with ARDS and increased WBC, high SGOT level, and increased PT indicative of liver injury and coagulopathy at the time of hospitalization are at high risk for mortality.

Risk and mediation analyses of hemoglobin glycation index and survival prognosis in patients with sepsis.

An increasing number of studies have reported the close relation of the hemoglobin glycation index (HGI) with metabolism, inflammation, and disease prognosis. However, the prognostic relationship between the HGI and patients with sepsis remains unclear. Thus, this study aimed to analyze the association between the HGI and all-cause mortality in patients with sepsis using data from the MIMIC-IV database. In this study, 2605 patients with sepsis were retrospectively analyzed. The linear regression equation was established by incorporating glycated hemoglobin (HbA1c) and fasting plasma glucose levels. Subsequently, the HGI was calculated based on the difference between the predicted and observed HbA1c levels. Furthermore, the HGI was divided into the following three groups using X-tile software: Q1 (HGI ≤ - 0.50%), Q2 (- 0.49% ≤ HGI ≤ 1.18%), and Q3 (HGI ≥ 1.19%). Kaplan-Meier survival curves were further plotted to analyze the differences in 28-day and 365-day mortality among patients with sepsis patients in these HGI groups. Multivariate corrected Cox proportional risk model and restricted cubic spline (RCS) were used. Lastly, mediation analysis was performed to assess the factors through which HGI affects sepsis prognosis. This study included 2605 patients with sepsis, and the 28-day and 365-day mortality rates were 19.7% and 38.9%, respectively. The Q3 group had the highest mortality risk at 28days (HR = 2.55, 95% CI: 1.89-3.44, p < 0.001) and 365days (HR = 1.59, 95% CI: 1.29-1.97, p < 0.001). In the fully adjusted multivariate Cox proportional hazards model, patients in the Q3 group still displayed the highest mortality rates at 28days (HR = 2.02, 95% CI: 1.45-2.80, p < 0.001) and 365days (HR = 1.28, 95% CI: 1.08-1.56, p < 0.001). The RCS analysis revealed that HGI was positively associated with adverse clinical outcomes. Finally, the mediation effect analysis demonstrated that the HGI might influence patient survival prognosis via multiple indicators related to the SOFA and SAPS II scores. There was a significant association between HGI and all-cause mortality in patients with sepsis, and patients with higher HGI values had a higher risk of death. Therefore, HGI can be used as a potential indicator to assess the prognostic risk of death in patients with sepsis.

Relationship between enteral nutrition timing and 28-day mortality in critically ill stroke patients in the MIMIC-IV database.

The ideal timing for commencing enteral nutrition (EN) in critically ill stroke patients in the intensive care unit (ICU) remains a subject of debate, with ongoing controversy regarding the impact of early EN (EEN) initiation. In this study, we investigated the association between the timing of EN initiation and 28-day mortality using data from the MIMIC-IV database. This study employed a retrospective cohort design using the MIMIC-IV database to identify stroke patients who received EN during their hospital stay. The main focus of this investigation was to examine 28-day mortality among these patients following hospital admission. Various demographic, clinical, laboratory, and intervention variables were considered as covariates. The Cox regression analysis was employed to assess the correlation between the timing of EN initiation and 28-day mortality, and restricted cubic splines (RCS) analysis was used to test for non-linear correlation. Patients were then stratified into two cohorts depending on the timing of EN initiation: within 2 days (n = 564) and beyond 2 days (n = 433). A multivariate Cox regression analysis was used to investigate the difference in 28-day mortality between the groups. A total of 997 participants were included in this study, with 318 (31.9%) dying within 28 days. We observed that the timing of EN initiation correlated with 28-day mortality, but this correlation was not significant after adjusting for covariates (crude HR: 0.94, 95% CI: 0.88-1, p = 0.044; adjusted HR: 0.96, 95% CI: 0.9-1.02, p = 0.178). The RCS analysis showed that the correlation was not non-linear. Notably, in the multivariate regression models, early EN initiation was associated with a higher mortality rate compared to late EN initiation [odds ratio (OR) = 1.34, 95% CI: 1.06-1.67, p = 0.012]. After adjusting for various confounding factors in the multivariate Cox regression models, we identified that patients in the early EN group had a 28% higher risk of mortality than those in the reference group (OR = 1.27, 95% CI: 1-1.61, p = 0.048). These associations remained consistent across various patient characteristics, as revealed through stratified analyses. Early commencement of EN in critically ill stroke patients may be linked to a higher risk of 28-day mortality, highlighting the need for further investigation and a more nuanced consideration of the optimal timing for commencing EN in this patient population.

Impact of prior oral anticoagulation therapies on post-discharge outcomes after COVID-19: Results from aglobal federated health network analysis.

The impact of chronic oral anticoagulant (OACs) use on long-term post-discharge outcomes after coronavirus disease 2019 (COVID-19) hospitalisation remains unclear. Herein, we compared clinical outcomes up to 2-years after COVID-19 hospitalisation between patients on vitamin K antagonists (VKAs), direct-acting OACs (DOACs) and no OAC therapy. Data from TriNetX, a global federated health research network, were used. Adult patients on VKAs, DOACs or no OAC therapy at diagnosis of COVID-19 between 20 January 2020 and 31 December 2021, who were hospitalised for COVID-19, were included. The primary outcomes were all-cause mortality, ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and the composite of intracranial haemorrhage (ICH)/gastrointestinal bleeding, at 2 years after COVID-19 hospitalisation. We included 110,834 patients with COVID-19. Following propensity score matching (PSM), we identified a decreased mortality risk in DOAC-treated patients compared to the no OAC cohort (RR .808, 95% CI .751-.870). A higher risk of ischaemic stroke/TIA/SE was observed in VKA users compared to DOAC users (RR 1.100, 95% CI 1.020-1.220) and in VKA users compared to patients not taking OAC (RR 1.400, 95% CI 1.140-1.720). VKA use was associated with a greater risk of ICH/gastrointestinal bleeding than DOAC users (RR 1.198, 95% CI 1.066-1.347), while DOAC users had a lower risk compared to no OAC-treated patients (RR .840, 95% CI .754-.936). COVID-19 patients taking prior DOACs were associated with lower long-term mortality risk and ICH/gastrointestinal bleeding than patients not taking OAC. Compared to patients on DOACs, VKA users were associated with higher risks of mortality, ischaemic stroke/TIA/SE and ICH/gastrointestinal bleeding.

Down syndrome and associated atrioventricular septal defects in a nationwide Norwegian cohort: Prevalence, time trends, and outcomes.

The prevalence of Down syndrome (DS) is approximately 1 per 1000 births and is influenced by increasing maternal age over the last few decades. DS is strongly associated with congenital heart defects (CHDs), especially atrioventricular septal defect (AVSD). Our objectives were to investigate the prevalence of live-born infants with DS having a severe CHD in the Norwegian population over the last 20 years and compare outcomes in infants with AVSD with and without DS. Information on all births from January 1, 2000 to December 31, 2019 was obtained from the Medical Birth Registry of Norway. We also obtained data on all infants with severe CHDs in Norway registered in Oslo University Hospital's Clinical Registry for Congenital Heart Defects during 2000-2019 and accessed individual-level patient data from the electronic hospital records of selected cases. Infants with AVSD and DS were compared to infants with AVSD without chromosomal defects. Crude and adjusted odds ratios (ORs) of infant mortality and need for surgery during the first year of life, with associated 95% confidence intervals (CIs), were estimated by logistic regression. A total of 1 177 926 infants were live-born in Norway during the study period. Among these, 1456 (0.1%) had DS. The prevalence of infants with DS having a severe CHDs was relatively stable, with a mean of 17 cases per year. The most common CHD associated with DS was AVSD (44.4%). Infants with AVSD and DS were more likely to have cardiac intervention during their first year of life compared to infants with AVSD without chromosomal defects (adjusted OR [aOR]: 2.52; 95% CI 1.27, 4.98). However, we observed no difference in infant mortality during first year of life between the two groups (aOR: 1.08; 95% CI 0.43, 2.70). The prevalence of live-born infants with severe CHDs and DS has been stable in Norway across 20 years. Infants with AVSD and DS did not have higher risk of mortality during their first year of life compared to infants with AVSD without chromosomal defects, despite a higher risk of operative intervention.

Novel Classification of Cardiovascular Disease Subtypes Reveals Associations Between Mortality and Polyunsaturated Fatty Acids: Insights from the United Kingdom Biobank Study

BackgroundTraditional association studies of cardiovascular disease (CVD) categorizations and polyunsaturated fatty acids (PUFAs) yielded conflicting findings. We propose a novel classification system based on fundamental characteristics of cardiovascular patients, such as age, body mass index, waist–hip ratio, to more accurately assess the impact of PUFAs (plasma measures) such as omega (ω)-3 (n–3) and ω-6 on mortality in cardiovascular patients. MethodsPrincipal component analysis and k-means clustering were used to determine the CVD subtype. Variables included age, body mass index, waist–hip ratio, diastolic blood pressure, systolic blood pressure, total cholesterol, total triglycerides, high-density lipoprotein-cholesterol, apolipoprotein B:apolipoprotein A1, glycated hemoglobin, creatinine, albumin, C-reactive protein, white blood cell count, platelet count, and hemoglobin concentration. The association of PUFAs with all-cause, cardiovascular, and ischemic heart disease (IHD) mortality in patients with CVD was prospectively evaluated using restricted cubic splines and Cox proportional risk models. ResultsAmong the 35,096 participants, 3,786 fatalities occurred. Three distinct CVD subtypes were identified, with cluster 3 characterized by older age, male gender, and low high-density lipoprotein-cholesterol, having the highest risk of mortality. Clusters 2 and 3 had the highest DHA and ω-6/ω-3 ratios, respectively, compared with Cluster 1. The protective effects of total PUFAs, ω-3, and DHA were mainly reflected in all-cause mortality and were more significant in clusters 2 and 3. Furthermore, the ω-6/ω-3 ratio of the highest quartile increased risk of all-cause [Q3: hazard ratio (HR): 1.14, 95% confidence interval [CI]: 1.00, 1.29; Q4: HR: 1.41, 95% CI: 1.24, 1.61], CVD (Q4: HR: 1.36, 95% CI: 1.07, 1.75), and IHD mortality (Q4: HR: 1.17, 95% CI: 1.12, 2.03) in cluster 3 compared with the first quartile. ConclusionsOur findings highlight the heterogeneity of associations observed for the same type of PUFAs across distinct clusters. This association may be elucidated by the intricate interplay of various factors, encompassing inflammation, lipid metabolism, and cardiovascular health.

Prehospital Post-Resuscitation Vital Sign Phenotypes are Associated with Outcomes Following Out-of-Hospital Cardiac Arrest

Objectives The use of machine learning to identify patient ‘clusters’ using post-return of spontaneous circulation (ROSC) vital signs may facilitate the identification of patient subgroups at high risk of rearrest and mortality. Our objective was to use k-means clustering to identify post-ROSC vital sign clusters and determine whether these clusters were associated with rearrest and mortality. Methods The ESO Data Collaborative 2018–2022 datasets were used for this study. We included adult, non-traumatic OHCA patients with >2 post-ROSC vital sign sets. Patients were excluded if they had an EMS-witnessed OHCA or were encountered during an interfacility transfer. Unsupervised (k-means) clustering was performed using minimum, maximum, and delta (last minus first) systolic blood pressure (BP), heart rate, SpO2, shock index, and pulse pressure. The assessed outcomes were mortality and rearrest. To explore the association between rearrest, mortality, and cluster, multivariable logistic regression modeling was used. Results Within our cohort of 12,320 patients, five clusters were identified. Patients in cluster 1 were hypertensive, patients in cluster 2 were normotensive, patients in cluster 3 were hypotensive and tachycardic (n = 2164; 17.6%), patients in cluster 4 were hypoxemic and exhibited increasing systolic BP, and patients in cluster 5 were severely hypoxemic and exhibited a declining systolic BP. The overall proportion of patients who experienced mortality stratified by cluster was 63.4% (c1), 68.1% (c2), 78.8% (c3), 84.8% (c4), and 86.6% (c5). In comparison to the cluster with the lowest mortality (c1), each other cluster was associated with greater odds of mortality and rearrest. Conclusions Unsupervised k-means clustering yielded 5 post-ROSC vital sign clusters that were associated with rearrest and mortality.

Abstract Mo049: Loss of Y chromosome and cardiovascular events in chronic kidney disease

Background: Chronic kidney disease represents one of the strongest risk factors for cardiovascular diseases, and particularly for heart failure. Despite improved pharmaceutical treatments mortality remains high. Recently, experimental studies demonstrated that mosaic loss of Y chromosome (LOY) associates with cardiac fibrosis in mice. Since diffuse cardiac fibrosis is the common denominator for progression of all forms of heart failure, we determined the association of LOY on mortality and cardiovascular disease outcomes in patients with chronic kidney disease. Methods: LOY was quantified in patients with stable CKD (CARE for HOMe study, derivation cohort, N=279) and dialysis patients (4D study, validation cohort, N=544). The association between LOY and mortality, combined cardiovascular and heart failure-specific endpoints, and echocardiographic measures was assessed. Results: In CARE for HOMe, mortality was higher in men as compared to women across the entire range of impaired renal function. The frequency of LOY increased with age. LOY was associated with increased mortality (HR 2.58, 95%CI 1.33-5.03) and risk for cardiac decompensation or death (HR 2.30, 95%CI 1.23-4.27). Patients with LOY &gt;17 % showed a significant decline of ejection fraction and an increase of E/E’ within five years. Consistently, validation in the 4D study revealed that LOY was associated with increased mortality (HR 3.13, 95%CI 1.97-4.99), higher risk of death due to heart failure and sudden cardiac death (HR 4.14, 95%CI 2.00-8.57), but not atherosclerotic events (see figure). Patients with LOY &gt;17 % showed significantly higher plasma levels of soluble ST2, a biomarker for myocardial fibrosis. Mechanistically, intermediate monocytes from patients with LOY &gt;17 % showed significantly higher CCR2 expression and higher plasma levels of the CCR2 ligand CCL2, which may have contributed to increased heart failure events. Conclusions: LOY identifies male patients with chronic kidney disease at high risk for mortality and heart failure events.

ARTEMIS: An independently validated prognostic prediction model of breast cancer incorporating epigenetic biomarkers with main effects and gene-gene interactions

IntroductionBreast cancer, a heterogeneous disease, is influenced by multiple genetic and epigenetic factors. The majority of prognostic models for breast cancer focus merely on the main effects of predictors, disregarding the crucial impacts of gene-gene interactions on prognosis. ObjectivesUsing DNA methylation data derived from nine independent breast cancer cohorts, we developed an independently validated prognostic prediction model of breast cancer incorporating epigenetic biomarkers with main effects and gene-gene interactions (ARTEMIS) with an innovative 3-D modeling strategy. ARTEMIS was evaluated for discrimination ability using area under the receiver operating characteristics curve (AUC), and calibration using expected and observed (E/O) ratio. Additionally, we conducted decision curve analysis to evaluate its clinical efficacy by net benefit (NB) and net reduction (NR). Furthermore, we conducted a systematic review to compare its performance with existing models. ResultsARTEMIS exhibited excellent risk stratification ability in identifying patients at high risk of mortality. Compared to those below the 25th percentile of ARTEMIS scores, patients with above the 90th percentile had significantly lower overall survival time (HR=15.43, 95 % CI: 9.57–24.88, P=3.06 × 10-29). ARTEMIS demonstrated satisfactory discrimination ability across four independent populations, with pooled AUC3-year = 0.844 (95 % CI: 0.805–0.883), AUC5-year = 0.816 (95 % CI: 0.775–0.857), and C-index = 0.803 (95 % CI: 0.776–0.830). Meanwhile, ARTEMIS had well calibration performance with pooled E/O ratio 1.060 (95 % CI: 1.038–1.083) and 1.090 (95 % CI: 1.057–1.122) for 3- and 5-year survival prediction, respectively. Additionally, ARTEMIS is a clinical instrument with acceptable cost-effectiveness for detecting breast cancer patients at high risk of mortality (Pt = 0.4: NB3-year = 0.019, NB5-year = 0.062; NR3-year = 69.21 %, NR5-year = 56.01 %). ARTEMIS has superior performance compared to existing models in terms of accuracy, extrapolation, and sample size, as indicated by the systematic review. ARTEMIS is implemented as an interactive online tool available at http://bigdata.njmu.edu.cn/ARTEMIS/. ConclusionARTEMIS is an efficient and practical tool for breast cancer prognostic prediction.

Management of Pulmonary Hypertension during Pregnancy

: Pregnancy in patients with pulmonary arterial hypertension (PAH) is a high-risk condition associated with high morbidity and mortality. Patients with severe PAH are often advised against pregnancy. Still, those patients who pursue pregnancy require a dedicated and multidisciplinary approach since the progression of fetal growth will accompany significant hemodynamic changes, which can be challenging for patients with a poorly functioning right ventricle. In this article, we describe the approach to the unique cardiovascular, respiratory, hematologic, and social challenges that pregnant patients with PAH face throughout pregnancy. We discuss the impact of these physiologic changes on diagnostic studies commonly used in PAH and how to incorporate diagnostic data in making the diagnosis and risk stratifying pregnant patients with PAH. The pharmacologic challenges of pulmonary vasodilators in pregnancy are discussed as well. Pregnant patients with PAH are at particularly high risk of mortality around the time of delivery, and we discuss the multidisciplinary approach to the management of these patients, including the use of anesthesia, inotropic support, type of delivery, and postpartum care, providing clinicians with a practical approach to the management of this difficult condition.

Activation of neurotoxic A1-reactive astrocytes by SFTS virus infection accelerates fatal brain damage in IFNAR1-/- mice.

Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1-/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1-/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach.

AB022. Management of first recurrence or progression of craniopharyngioma after resection alone: a systematic review and individual-participant data meta-analysis.

The initial management of craniopharyngioma is generally either gross total resection (GTR) or subtotal resection (STR) with adjuvant radiotherapy (RT). However, the optimal management strategy for recurrent/progressive craniopharyngioma remains unclear. PubMed and Embase were systematically reviewed for studies that compared the outcomes of surgery and/or RT for the first recurrence/progression of craniopharyngioma after resection alone. The exposure was the treatment that was administered for the first recurrence/progression, and the outcomes were tumor regrowth and overall survival (OS). Subgroup analyses were performed by age at the treatment for the first recurrence/progression (<18 or ≥18 years old), duration between the first treatment and the first recurrence/progression (<2 or ≥2 years), and the initial treatment that was administered (STR or GTR). Of the 2,932 studies screened, 11 studies reporting a total of 80 patients were included. Across almost all subgroups, patients who received RT for the first recurrence/progression had a significantly lower risk of tumor regrowth than those who did not, regardless of whether surgery was performed and the extent of resection. There was no significant association between the treatment administered for the first recurrence/progression and OS, except for patients with a recurrence/progression <2 years after the first treatment, where GTR was associated with a higher risk of mortality. For patients with the first recurrence/progression of craniopharyngioma after resection alone, RT should be considered for better local control. In cases where RT is not administered, GTR is preferred over STR provided it can be safely performed, for improved local control.

Impact of Long-Term Non-Communicable Diseases on SARS-COV-2 Hospitalized Patients Supported by Radiological Imaging in Southern Pakistan.

COVID-19 patients with already existing chronic medical conditions are more likely to develop severe complications and, ultimately, a higher risk of mortality. This study analyzes the impacts of pre-existing chronic illnesses such as diabetes (DM), hypertension, and cardiovascular diseases (CVDs) on COVID-19 cases by using radiological chest imaging. The data of laboratory-confirmed COVID-19-infected hospitalized patients were analyzed from March 2020 to December 2020. Chest X-ray images were included to further identify the differences in X-ray patterns of patients with co-morbid conditions and without any co-morbidity. The Pearson chi-square test checks the significance of the association between co-morbidities and mortality. The magnitude and dimension of the association were calibrated by the odds ratio (OR) at a 95% confidence interval (95% CI) over the patients' status (mortality and discharged cases). A univariate binary logistic regression model was applied to examine the impact of co-morbidities on death cases independently. A multivariate binary logistic regression model was applied for the adjusted effects of possible confounders. For the sensitivity analysis of the model, receiver operating characteristic (ROC) was applied. Patients with different comorbidities, including diabetes (OR = 33.4, 95% CI: 20.31-54.78, p < 0.001), cardiovascular conditions (OR = 24.14, 95% CI: 10.18-57.73, p < 0.001), and hypertension (OR = 16.9, 95% CI: 10.20-27.33,p < 0.001), showed strong and significant associations. The opacities present in various zones of the lungs clearly show that COVID-19 patients with chronic illnesses such as diabetes, hypertension, cardiovascular disease, and obesity experience significantly worse outcomes, as evidenced by chest X-rays showing increased pneumonia and deterioration. Therefore, stringent precautions and a global public health campaign are crucial to reducing mortality in these high-risk groups.

Open ankle fractures in the elderly: predisposing factors and the associated mortality.

The purpose of this study was to investigate the independent effect of open ankle fractures on postoperative mortality and to identify factors leading to open ankle fractures in the elderly population. This is a retrospective case-control study of 1,045 patients aged 65years and older, with ankle fractures undergoing surgical fixation between 2010 and 2020 at three medical centers (Levels 1-2). A logistic regression analysis was used to identify risk factors for open fractures. Propensity score matching and survival analysis were used to measure the hazard of mortality attributable to open versus closed ankle fractures. There were 128 (12.2%) patients with open ankle fractures. Patients with open ankle fractures were more likely to be older, to be active smokers (OR = 1.7, p = 0.049), and tended to have a higher number of medical comorbidities including hypertension (OR = 2, p = 0.006) and chronic kidney disease (OR = 2.9, p = 0.005). Open ankle fractures were, independently of comorbid conditions and age, associated with higher risk of mortality (HR = 1.7, p = 0.03).