Prognosis Of Failure Research Articles

Correlation between serum laminin level and prognosis of acute heart failure.

To investigate the correlation between serum laminin (LN) level and the prognosis of acute heart failure (AHF). A total of 199 patients with AHF treated in Nantong First People's Hospital from March 2019 to November 2021 were included in this study. The patients were divided into the event group and the non-event group according to whether major adverse cardiovascular events (MACEs) occurred during hospitalization. We collected the baseline data of all patients and their LN levels were measured. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of LN for the occurrence of MACE in AHF patients during hospitalization. Multivariate Logistic regression analysis was used to screen the independent factors associated with the occurrence of MACE in patients with AHF. Among 199 patients with AHF, 43 were in the event group and 156 were in the non-event group. The area under ROC curve of LN to predict MACE in AHF patients during hospitalization was 0.8144, 95% confidence interval (CI): 0.7433-0.8855, p < .0001, cutoff point = 77.9, specificity 58.33%, and sensitivity 88.37%. Multivariate logistic regression analysis showed that the independent factors associated with the occurrence of MACE in AHF patients were the increase of LN level (odds ratio [OR]: 1.020, 95%CI: 1.012-1.028), the decrease of ejection fraction (OR: 0.007, 95%CI: 0.000-0.362) and diastolic blood pressure (OR: 0.946, 95%CI: 0.913-0.981;p < .05). The increase of LN level is independently correlated with the occurrence of MACE in AHF patients during hospitalization, which has the potential to be a serological indicator for poor prognosis in patients with AHF.

Progress in Metastasis and Treatment of Osteosarcoma

Osteosarcoma is a primary malignant tumor originating from mesenchymal tissue. It has the characteristics of high malignancy, easy metastasis (common lung metastasis) and poor prognosis. Metastasis is the main cause of treatment failure and poor prognosis. Although the treatment of osteosarcoma has made some progress in these decades, the 5-year survival rate of patients with metastasis has not increased much. This review explores the molecular mechanism of osteosarcoma metastasis, the current research progress of therapeutic drugs, immunotherapy and targeted therapy, and provides ideas for the treatment of osteosarcoma.

Clinical characteristics and prognosis of non-APAP drug-induced acute liver failure: a large multicenter cohort study

BackgroundThere is growing recognition of natural history, complications, and outcomes of patients who develop non-acetaminophen (APAP) drug-induced acute liver failure (ALF). To clarify high-risk factors and develop a nomogram model to predict transplant-free survival (TFS) in patients with non-APAP drug-induced ALF.MethodsPatients with non-APAP drug-induced ALF from 5 participating centers were retrospectively analyzed. The primary endpoint was 21-day TFS. Total sample size was 482 patients.ResultsRegarding causative agents, the most common implicated drugs were herbal and dietary supplements (HDS) (57.0%). The hepatocellular type (R ≥ 5) was the main liver injury pattern (69.0%). International normalized ratio, hepatic encephalopathy grades, the use of vasopressor, N-acetylcysteine, or artificial liver support system were associated with TFS and incorporated to construct a nomogram model (drug-induced acute liver failure-5, DIALF-5). The AUROC of DIALF-5 for 7-day, 21-day, 60-day, and 90-day TFS in the internal cohort were 0.886, 0.915, 0.920, and 0.912, respectively. Moreover, the AUROC of DIALF-5 for 21-day TFS had the highest AUROC, which was significantly higher than 0.725 of MELD and 0.519 of KCC (p < 0.05), numerically higher than 0.905 of ALFSG-PI but without statistical difference (p > 0.05). These results were successfully validated in the external cohort (147 patients).ConclusionsBased on easily identifiable clinical data, the novel DIALF-5 model was developed to predict transplant-free survival in non-APAP drug-induced ALF, which was superior to KCC, MELD and had a similar prediction performance to ALFSG-PI but is more convenient, which can directly calculate TFS at multiple time points.

Low atrial natriuretic peptide to brain natriuretic peptide ratio is associated with left atrial remodeling.

Atrial natriuretic peptide (ANP) deficiency is thought to be one of the causes of heart failure induced by atrial fibrillation (AF). Although ANP deficiency is thought to occur as a result of atrial remodeling, data to explain this mechanism are limited. The purpose of this study was to investigate the association between ANP and left atrial remodeling or prognosis of heart failure in patients with AF ablation. In total, 373 consecutive patients who underwent initial ablation for persistent AF [age, 67 ± 10 years; female, 97 (26%)] were retrospectively enrolled. ANP and brain natriuretic peptide (BNP) were measured before the procedure and the ANP/BNP ratio was calculated. Left atrial volume index, left atrial appendage emptying velocity, and left atrial low-voltage areas (LVAs) were used as left atrial-remodeling parameters. The primary outcome of heart failure was defined as the composite of all-cause death or hospitalization due to worsening heart failure. The median ANP level was 116 (71-178) pg/ml and the median ANP/BNP ratio was 0.65 (0.46-1.00). The ANP/BNP ratio decreased with increasing left atrial volume index or LVAs and with decreasing left atrial appendage emptying velocity. During the 5-year follow-up, freedom from the primary outcome was significantly lower in patients with ANP/BNP ratio ≤0.65 than in those with ANP/BNP ratio >0.65 (84.6% versus 95.6%, P < 0.01). Secretion of ANP relative to BNP decreased with progression of left atrial remodeling in patients with AF ablation. Furthermore, prognosis of heart failure was poor in patients with a low ANP/BNP ratio.

Ratio between right ventricular longitudinal strain and pulmonary arterial systolic pressure: A novel prognostic parameter in patients with severe tricuspid regurgitation

BackgroundIn terms of pathophysiology, tricuspid regurgitation (TR), right ventricular function and pulmonary artery pressure are linked to each other. Our aim was to analyze whether the echocardiography-derived right ventricular free wall longitudinal strain/pulmonary artery systolic pressures (RVFWLS/PASP) ratio can improve risk stratification in patients with severe tricuspid regurgitation (TR). MethodsIn this single-center retrospective study, 250 consecutive patients with severe TR were enrolled from December 2015 to December 2018. Baseline clinical and echocardiographic parameters were collected. Echocardiography-derived TAPSE/PASP and RVFWLS/PASP were evaluated. The primary endpoint was all-cause mortality. ResultsOut of 250 consecutive patients, 171 meet inclusion criteria. Patients were predominantly female, with several cardiovascular risk factors and comorbidities. RVFWLS/PASP ≤0.34%/mmHg (AUC 0.68, p < 0.001, sensitivity 70%, specificity 67%) was associated with baseline clinical RV heart failure (p = 0.03). After univariate and multivariate analyses, RVFWLS/PASP, but not TAPSE/PASP, independently correlated with all-cause mortality (HR 0.004, p = 0.02). Patients with RVFWLS/PASP >0.26%/mmHg (AUC 0.74, p < 0.001, sensitivity 77%, specificity 52%) showed higher survival rates (p = 0.02). In addition at 24 months follow-up, the Kaplan-Meyer curves showed patients with RVFWLS >14% & RVFWLS/PASP >0.26%/mmHg had the best survival rate compared to patients without. ConclusionRVFWLS/PASP is independently associated with baseline RV heart failure and poor long-term prognosis in patients with severe TR.

Usefulness of the Klotho protein, FGF-23 and GDF-15 in assessment of the new onset Acute Heart Failure

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by a grant from the Institute of Medical Sciences, University of Opole, Poland. Background Acute heart failure (AHF) is a life-threatening multifaceted clinical condition requiring intensive and expensive treatment. Earlier studies highlighted the difference in characteristics and prognosis of new onset AHF (NO- AHF) and acute decompensated heart failure (ADHF). Protein Klotho and FGF23 could be attractive tools in the evaluation of patients with AHF. GDF-15 is a recognized marker of the risk of death and complications, including bleeding in many cardiovascular diseases. Aim The aim of the study was to compare selected biomarkers (Protein Klotho, FGF-23, GDF-15) with clinical characteristics and 12-month outcomes of patients with NO-AHF and ADHF. Methods As part of the prospective Acute Heart Failure Registry (OP-AHF), data from 112 patients hospitalized in Intensive Cardiac Care Unit (ICCU) were collected from June 2019. Inclusion criteria were: hospitalization for AHF and the use of at least one of: intravenous diuretics, catecholamines or mechanical circulatory support. Blood samples were collected on admission, at discharge as well as at the 30-day. Patients were than follow-up for one year. Results Patients with NO-AHF constituted 46% of the study group (52 out of 112) and compared to patients with ADHF they were more often aged under 65 years (44% vs. 30%, p=0.12), better educated (25% vs. 8%, p=0.03), less frequently with diabetes (31% vs. 43%, p=0.17), hypertension (58% vs. 83%, p=0.03), and prior myocardial infarction (19% vs. 45%, p=0.004). In both groups there were more men (69% vs. 80%,p=0.19) and ischemic etiology of heart failure were more frequent (33% vs. 51%, p=0.42) in NO-AHF and ADHF, respectively. Left ventricular ejection fraction (LVEF) was insignificantly higher in patients with NO-AHF on admission (30% vs. 26%, p=0.6) and at discharge (35% vs. 30%, p=0.27).Only patient with NO-AHF improved LVEF at the 12- month follow–up (50% vs. 35%, p=0,003).It was no signifcant differences between median value of Klotho protein in both groups at admission, discharge and 30–day follow up visit. We observed significant reduction in FGF-23 and GDF-16 at tree time points (Table 1). 12-month mortality in patients with NO-AHF was insignificantly lower (17% vs. 28% in ADHF HR=1,7 (95% Cl=0.25-1.18)),also after correction for age, sex and ,LVEF- 20% vs. 25%, respectively, p=0.58; HR=1,26 (0.3-1.8). In the Cox multivariate model, the risk of death was presented as hazard ratio (HR) and was highest for GDF-15 in both groups (Table2). Conclusion Patients with the NO- AHF have different clinical profile than patients with acute decompensated heart failure with a tendency to lower 12-month mortality. There were no significant differences in the median value of Klotho protein in both groups. Reduction of the FGF-23 during hospitalization can serve as a marker of AHF compensation, thus FGF-23 could be a valuable tool for assessing response to treatment. GDF-15 seems to be the strongest predictor of death in both groups of AHF.

Meta-analysis of prevalence and prognosis of AHF in patients admitted with myocardial infarction: role of invasive management in determining patients' outcomes.

This meta-analysis aimed to reveal the prevalence and prognosis of heart failure in myocardial patients. This study further sought to explore the role of treatment in determining outcomes. This systematic analysis was performed on the principles of the pre-designed protocol of meta-analysis and systematic reviews statement. Online search articles were accessed for analysis. Studies from January 2012 to August 2020 were considered to identify the prognosis and prevalence of acute heart failure and myocardial infarction. Cochran's Q-test and I2-test were used to measure heterogeneity across the studies. Meta-regression was also performed to identify the potential source of heterogeneity. For the final analysis, 30 studies were included. No significant publication bias was reported on the funnel plot. However, a 0.462 value was reported for short-term mortality, whereas 0.274 was reported for the long term while performing Egger's tests. Meanwhile, the Begg test showed a value of 0.274 for publication bias. However, an asymmetrical funnel plot suggested potential publication bias. After adjustment of clinical and cardiovascular baseline, significant results related to the impact of sex differences on mortality could be obtained. Disease prognosis may be affected by co-morbidities, especially diabetes Mellitus, kidney disease, hypertension, and COPD worsening the situation of patients.

Ceftazidime/Avibactam, Polymyxin or Tigecycline as a Rescue Strategy for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae in Bloodstream Infection: A Retrospective Cohort Study.

To analyze the clinical characteristics, outcomes, and risk factors of patients treated with ceftazidime/avibactam, polymyxin, or tigecycline (CPT) compared with those receiving a conventional therapy (CT) (ie, imipenem, levofloxacin, or gentamicin). A single-center retrospective cohort study included patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) treated at one Chinese tertiary hospital between March 2012 and November 2022 was performed. Clinical characteristics, outcomes, and risk factors of patients treated with CPT or CT were compared. Predictors of 30-day mortality of patients with CRKP-BSI were also analysed in our study. Among 184 recruited patients with CRKP-BSI, 39.7% (73/184) were treated with CPT, while 60.3% (111/184) were treated with CT. Compared to patients treated with CT, patients treated with CPT had worse conditions, as evidenced by a higher rate of underlying diseases and invasive procedures; however, they also had a better prognosis and lower rates of 14-day treatment failure (p = 0.024). In addition, univariate analysis and multivariate analysis showed that SOFA score [odds ratio (OR) = 1.310, 95% confidence interval (CI) 1.157-1.483; p < 0.001] and cold weather (OR = 3.658, 95% CI 1.474-9.081; p = 0.005) were independent risk factors for 30-day mortality. Compared to CRKP-BSI patients treated with CT, patients treated with CPT had worse conditions but better prognoses. CRKP-BSI occurred more frequently in hot weather; however, higher 30-day mortality was associated with cold weather. A randomized trial is needed to confirm these observational results.

Brain estrogen receptor may have a protective effect against heart failure progression in an ischemic heart failure model

Background: Women appear to have a better prognosis of heart failure compared to men. Estrogen, a major sex hormone, can cross the blood-brain barrier, and the signaling through estrogen receptor in the brain may have a sympathoinhibitory effect. Sympathoexcitation is crucially involved in the progression of heart failure. Therefore, we investigated whether the brain estrogen receptors have a protective effect against heart failure in an ischemic heart failure model. Since estrogen has been reported to inhibit microglial activation, we also evaluated the changes in microglia and brain inflammation induced by the estrogen receptor-mediated signaling. Methods: Female C57BL/6J mice underwent coronary ligation to induce myocardial infarction (MI). One week after MI, the intracerebroventricular infusion of ICI 182,780, an estrogen receptor inhibitor (ERi), or vehicle was initiated for 3 weeks. Sham-operated mice with vehicle treatment were used as normal control. Four weeks after MI, echocardiography was performed and the tissues were collected. Results: After the randomization of intracerebroventricular treatment, 78% (n=14 in 18 [four survival mice]) of mice died in the MI mice treated with ERi (MI-ERi group), while there was no death in normal control group (n=7) and MI-vehicle group (n=7). In echocardiography, increased left ventricular end-diastolic diameter (LVDd) and decreased fractional shortening (FS) were similarly observed in MI-vehicle and MI-ERi groups compared to control group (LVDd: control 3.4±0.05 mm, MI-vehicle 5.3±0.19 mm, MI-ERi 5.7[KS1] ±0.28 mm; FS: control 33.7±0.8[KS2] %, MI-vehicle 8.5±1.4 %, MI-ERi 5.7±1.0 %; p&lt;0.05 vs control). Heart weight and lung weight were significantly increased in MI-vehicle and MI-ERi groups than control group, while there was no difference between the two MI groups. (heart weight: control 95.3±1.5[KS3] mg, MI-vehicle 165.9±7.6 mg, MI-ERi 164.7±6.3 mg; lung weight: control 115.6±1.1 mg, MI-vehicle 141.0±6.0 mg, MI-ERi 190.8±33.7 mg; p&lt;0.05 vs control). In the hypothalamus, the mRNA expression of Iba-1 and CD68, a marker of microglia and activated microglia/macrophages, respectively, was increased in the two MI groups compared to control group. Furthermore, the Iba-1 expression was significantly increased (p&lt;0.01) and the CD68 expression tended to be increased (p=0.051) in MI-ERi group compared to MI-vehicle group. The expression of interleukin-1β and interleukin-6 was also increased in the two MI groups compared to controls, without significant difference between the two MI groups. Conclusion: Inhibition of the brain estrogen receptor after MI significantly increased the mortality, while there was no significant difference in phenotypes of heart failure between the survived mice on ERi treatment and the vehicle-treated mice. These preliminary data suggest that brain estrogen receptor might play a role in protecting against heart failure. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Proteomics and phosphoproteomics of failing human left ventricle identifies dilated cardiomyopathy-associated phosphorylation of CTNNA3

The prognosis and treatment outcomes of heart failure (HF) patients rely heavily on disease etiology, yet the majority of underlying signaling mechanisms are complex and not fully elucidated. Phosphorylation is a major point of protein regulation with rapid and profound effects on the function and activity of protein networks. Currently, there is a lack of comprehensive proteomic and phosphoproteomic studies examining cardiac tissue from HF patients with either dilated dilated cardiomyopathy (DCM) or ischemiccardiomyopathy (ICM). Here, we used a combined proteomic and phosphoproteomic approach to identify and quantify more than 5,000 total proteins with greater than 13,000 corresponding phosphorylation sites across explanted left ventricle (LV) tissue samples, including HF patients with DCM vs. nonfailing controls (NFC), and left ventricular infarct vs. noninfarct, and periinfarct vs. noninfarct regions of HF patients with ICM. Each pair-wise comparison revealed unique global proteomic and phosphoproteomic profiles with both shared and etiology-specific perturbations. With this approach, we identified a DCM-associated hyperphosphorylation cluster in the cardiomyocyte intercalated disc (ICD) protein, αT-catenin (CTNNA3). We demonstrate using both exvivo isolated cardiomyocytes and invivo using an AAV9-mediated overexpression mouse model, that CTNNA3 phosphorylation at these residues plays a key role in maintaining protein localization at the cardiomyocyte ICD to regulate conductance and cell-cell adhesion. Collectively, this integrative proteomic/phosphoproteomic approach identifies region- and etiology-associated signaling pathways in human HF and describes a role for CTNNA3 phosphorylation in the pathophysiology of DCM.

EBF1 Promotes the Sensitivity of Cervical Cancer Cells to Cisplatin via Activating FBN1 Transcription

Cisplatin (DDP) is widely used in the chemotherapy of cervical cancer (CC), the fourth most common female malignancy worldwide. However, some patients progress to chemotherapy resistance, which leads to chemotherapy failure, tumor recurrence, and poor prognosis. Therefore, strategies to identify the regulatory mechanisms underlying CC development and increase tumor sensitivity to DDP will help improve patient survival. This research was designed to ascertain the mechanism of EBF1-dependent regulation of FBN1 which promotes chemosensitivity of CC cells. The expression of EBF1 and FBN1 was measured in CC tissues resistant or sensitive to chemotherapy and in DDP-sensitive or -resistant cells (SiHa and SiHa-DDP cells). SiHa-DDP cells were transduced with lentiviruses encoding EBF1 or FBN1 to evaluate the influence of these two proteins on cell viability, expression of MDR1 and MRP1, and cell aggressiveness. Moreover, the interaction between EBF1 and FBN1 was predicted and demonstrated. Finally, to further verify the EBF1/FB1-dependent mechanism of DDP sensitivity regulation in CC cells a xenograft mouse model of CC was established using SiHa-DDP cells transduced with lentiviruses carrying EBF1 gene and shRNA directed to FBN1.EBF1 and FBN1 showed decreased expression in CC tissues and cells, particularly in those resistant to chemotherapy. Transduction of SiHa-DDP cells with lentiviruses encoding EBF1 or FBN1 lead to decreased viability, IC50, proliferation capacity, colony formation ability, aggressiveness, and increased cell apoptosis. We have shown that EBF1 activates FBN1 transcription by binding to FBN1 promoter region. Additionally, it was revealed that FBN1 silencing reversed the promoting effect of EBF1 overexpression on chemosensitivity of CC cells in vivo. EBF1 facilitated chemosensitivity in CC cells by activating FBN1 transcription.

Serum Dynamin-Related Protein 1 Concentrations Discriminate Phenotypes and Predict Prognosis of Heart Failure.

Dynamin-related protein 1 (Drp1) has been demonstrated as a crucial role in mediating the programed cell death and cardiac metabolism through its regulatory of mitophagy in animal studies. However, the clinical values of Drp1 for human cardiac disease remain unknown. This study is aimed to evaluate the diagnostic and prognostic values of serum Drp1 in these patients with heart failure (HF). The enzyme linked immunosorbent assay (ELISA) was used for measuring serum Drp1 concentrations in 85 cases of HF with preserved ejection fraction (HFpEF) and 86 cases of HF with reduced ejection fraction (HFrEF). The diagnostic value of Drp1 was evaluated using the receiver operating characteristic (ROC) analysis. The composite endpoint was consisted of cardiac death and rehospitalization for HF, and the association between Drp1 and clinical outcomes were further determined. Serum Drp1 concentrations were much higher in HFpEF than that in HFrEF (4.2 3.7 ng/mL vs. 2.6 2.2 ng/mL, p = 0.001) and the ROC analysis demonstrated it as a potential diagnostic biomarker for distinction of the HF phenotypes, with an optimal cutoff point of 3.5 ng/mL (area under the curve (AUC) = 0.659, sensitivity: 45.9%, specificity: 83.7%). Kaplan-Meier survival analysis indicated that a low serum concentration of Drp1 (cut-off value = 2.5 ng/mL, AUC = 0.738) was in relation to poor prognosis of HF. Moreover, binary logistic regression analysis identified the low serum concentration of Drp1 as an independent risk predictor for rehospitalization (odds ratio (OR) = 6.574, p = 0.001) and a composite endpoint (OR = 5.927, p = 0.001). Our findings suggested that low serum concentrations of Drp1 might serve as a predicting biomarker for distinction of HF phenotypes and overall prognosis of HF.

Coronary Artery Disease and Prognosis of Heart Failure with Reduced Ejection Fraction.

Our aim was to determine the prognostic impact of coronary artery disease (CAD) on heart failure with reduced ejection fraction (HFrEF) mortality and readmissions. From a prospective multicenter registry that included 1831 patients hospitalized due to heart failure, 583 had a left ventricular ejection fraction of <40%. In total, 266 patients (45.6%) had coronary artery disease as main etiology and 137 (23.5%) had idiopathic dilated cardiomyopathy (DCM), and they are the focus of this study. Significant differences were found in Charlson index (CAD 4.4 ± 2.8, idiopathic DCM 2.9 ± 2.4, p < 0.001), and in the number of previous hospitalizations (1.1 ± 1, 0.8 ± 1.2, respectively, p = 0.015). One-year mortality was similar in the two groups: idiopathic DCM (hazard ratio [HR] = 1), CAD (HR 1.50; 95% CI 0.83-2.70, p = 0.182). Mortality/readmissions were also comparable: CAD (HR 0.96; 95% CI 0.64-1.41, p = 0.81). Patients with idiopathic DCM had a higher probability of receiving a heart transplant than those with CAD (HR 4.6; 95% CI 1.4-13.4, p = 0.012). The prognosis of HFrEF is similar in patients with CAD etiology and in those with idiopathic DCM. Patients with idiopathic DCM were more prone to receive heart transplant.

Abstract 3501: A genome-wide screen for determinants of radioresistance in head and neck cancer

Abstract Introduction: Head and neck cancer (HNC) is the seventh most common cancer worldwide with over 1 million new cases diagnosed each year. Radioresistance is a major cause of both treatment failure and poor prognosis, with locoregional recurrence after radiotherapy occurring in up to 50% of HNC patients. Despite the discovery of individual genes implicated in the ability of HNC cells to develop radioresistance, a systematic evaluation remains to be undertaken. This project is the first to conduct genome-wide CRISPR screens for regulators of radioresistance in HNC, with the aim to identify phenotype-driving genes and pathways. Experimental Procedures: Genome-wide negative selection screens were conducted on HNC cell lines using the Toronto KnockOut (TKO) CRISPR library. Monoclonal Cas9 cell lines were derived from UT-SCC-42A (42A), FaDu, and PE/CA-PJ41 (clone D2) with Cas9 editing efficiencies &amp;gt;80%. Library-transduced cells were treated with the minimum dose of radiation resulting in cessation of cell growth (10 Gy for 42A and FaDu; 8 Gy for PE/CA-PJ41). Genomic DNA from the resultant radioresistant populations was extracted and sequenced on the Illumina NextSeq 500. MAGeCK analysis of read counts identified gene targets of significantly depleted gRNAs after irradiation. Genes that correlated with overall survival (OS) in the TCGA Pan-Cancer database were selected for further investigation. The top candidate genes in the determination of radioresponse were validated using cell proliferation and clonogenic assays. Effects of loss-of-function on cell migration were assessed using scratch wound and transwell migration assays. Results: 117 putative radioresistance genes were identified in the 42A cell line screen; the top ranked hits were MMP14, CD44, CALR, and HHLA1. RNA expression levels of these genes had a significant correlation with OS of radiation-treated HNC patients in the TCGA Pan-Cancer Atlas. Loss-of-function of the candidate genes was confirmed to increase radiosensitivity through live cell imaging in 42A and PJ41 cells, which were further corroborated with clonogenic assays. Downregulation of at least one gene impaired the migration of 42A and PJ41 cells, suggesting a role in cellular invasion and migration. Conclusion: This study will contribute to a deeper understanding of mechanisms of radioresistance in HNC, which continues to be a leading cause of mortality in HNC patients. Future pathway elucidation through transcriptome analysis and functional characterization may reveal additional therapeutic targets that can improve the outcome for HNC patients treated with radiation. Citation Format: Jacqueline H. Law, Pierre-Antoine Bissey, Isabella Kojundzic, Kenneth W. Yip, Fei-Fei Liu. A genome-wide screen for determinants of radioresistance in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3501.

Is the Naples prognostic score useful for predicting heart failure mortality.

Aim The Naples prognostic score (NPS) simultaneously evaluates inflammation and malnutrition, which are two main factors that play a role in the pathophysiology and prognosis of heart failure (HF). In this study, we aimed to examine the relationship of NPS with in-hospital mortality of hospitalized patients with a diagnosis of HF.Material and Methods A total of 496 hospitalized HF patients included in this study. The patients were divided into two groups as deceased and living. The clinical and demographic characteristics of each patient were recorded. NPS of each patient was calculated.Results NPS was significantly higher in the deceased group compared to the living group (3.6±0.61, 3.21±0.97, respectively; p=0.003). According to multivariate regression analysis: NPS (OR: 1.546, 95 % CI: 1.027-2.327; p=0.037), systolic blood pressure (OR: 0.976, 95 % CI: 0.957-0.995; p=0.015), and white blood cell count (OR: 1.072, 95 % CI: 1.007-1142; p=0.03) are independent predictors for in-hospital mortality in HF patients.Conclusion This study demonstrated a strong correlation between NPS and mortality in HF. This new score can be used to predict the prognosis of HF as it shows both the level of inflammation and nutrition.

Natriuretic Peptides as Biomarkers: Narrative Review and Considerations in Cardiovascular and Respiratory Dysfunctions.

Natriuretic peptides (NPs) encompass a family of structurally related hormone/paracrine factors acting through the natriuretic peptide system regulating cell proliferation, vessel tone, inflammatory processes, neurohumoral pathways, fluids, and electrolyte balance. The three most studied peptides are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-Type natriuretic peptide (CNP). ANP and BNP are the most relevant NPs as biomarkers for the diagnosis and prognosis of heart failure and underlying cardiovascular diseases, such as cardiac valvular dysfunction, hypertension, coronary artery disease, myocardial infarction, persistent arrhythmias, and cardiomyopathies. Cardiac dysfunctions related to cardiomyocytes stretching in the atria and ventricles are primary elicitors of ANP and BNP release, respectively. ANP and BNP would serve as biomarkers for differentiating cardiac versus noncardiac causes of dyspnea and as a tool for measuring the prognosis of patients with heart failure; nevertheless, BNP has been shown with the highest predictive value, particularly related to pulmonary disorders. Plasma BNP has been reported to help differentiate cardiac from pulmonary etiologies of dyspnea in adults and neonates. Studies have shown that COVID-19 infection also increases serum levels of N-terminal pro b-type natriuretic peptide (NT-proBNP) and BNP. This narrative review assesses aspects of ANP and BNP on their physiology, and predictive values as biomarkers. We present an overview of the NPs' synthesis, structure, storage, and release, as well as receptors and physiological roles. Following, considerations focus on ANP versus BNP, comparing their relevance in settings and diseases associated with respiratory dysfunctions. Finally, we compiled data from guidelines for using BNP as a biomarker in dyspneic patients with cardiac dysfunction, including its considerations in COVID-19.

PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression

Triple-negative breast cancer (TNBC) is a type of breast malignancy characterized by a high proliferative rate and metastatic potential leading to treatment failure, relapse, and poor prognosis. Therefore, efforts are continuously being devoted to understanding its biology and identifying new potential targets. Programmed death-ligand 1 (PD-L1) is an immunosuppressive protein that inactivates T cells by binding to the inhibitory receptor programmed death-1 (PD-1). PD-L1 overexpression in cancer cells contributes to immune evasion and, subsequently, poor survival and prognosis in several cancers, including breast cancer. Apart from its inhibitory impact on T cells, this ligand is believed to have an intrinsic role in cancer cells. This study was performed to clarify the PD-1 independent role of PD-L1 in TNBC MDA-MB-231 cells by knocking out the PD-L1 using three designs of CRISPR-Cas9 lentiviral particles. Our study revealed that PD-L1 knockout significantly inhibited MDA-MB-231 cell proliferation and colony formation in vitro and tumor growth in the chick embryo chorioallantoic membrane (CAM) model in vivo. PD-L1 knockout also decreased the migration and invasion of MDA-MB-231 cells in vitro. We have shown that PD-L1 knockout MDA-MB-231 cells have low levels of p-Akt and p-ERK in addition to some of their downstream proteins, c-Fos, c-Myc, p21, survivin, and COX-2. Furthermore, PD-L1 knockout significantly decreased the expression of Snail and RhoA. This study shows the intrinsic role of PD-L1 in TNBC independently of its binding to PD-1 receptors on T cells. It may pave the way for developing novel therapeutic strategies using PD-L1 inhibitors alone and in combination to treat TNBC more effectively.

Reliability modeling and maintenance planning for a parallel system with respect to the state-dependent mean residual time

Parallel configuration is one of the most important structures for complex systems. Due to its role in reliability analysis, there has been a growing interest in using the mean residual lifetime as index of the failure prognosis and also maintenance planning. When inspections of the system are involved, mean residual life can be improved through incorporating the information gathered in the inspection times. In this article, maintenance actions are performed based on a mean residual time index and the information about the number of failed components gathered in the inspection times. The main novelty of this article is that the mean residual time is computed as the expected remaining time to reach a defective state instead of the expected remaining time to reach the system failure. Different properties of the expected remaining time to reach a defective state are shown in this article. Based on the expected remaining time to reach a defective state, two maintenance models (Model I and Model) are developed. Compared to Model I, Model II allows the inclusion of minimal repairs. Different numerical examples are computed to highlight distinctions between the two models.

Angiopoietin-1 as a marker of endothelial dysfunction and a risk factor for acute kidney injury in patients with COVID-19: retrospective cohort study

Recently, data have been published on the leading role of endothelial dysfunction in the development of severe COVID-19, including acute renal failure (AKI) and poor prognosis in this group of patients.Aim. To define the role of angiopoetin-1(Ang-1) as a marker of endothelial dysfunction in development of AKI in patients, hospitalized with COVID-19.Materials and methods. 76 patients with confirmed coronavirus infection were included in the study. AKI was diagnosed according to KDIGO 2012 criteria in 44 patients (group 1), 32 patients without sings of kidney disfunction were in group 2. Beside standard clinical and laboratory markers on admission we evaluated serum Ang-1 level with ELISA. We used regression analysis for AKI risk factors evaluation, we calculated odds ratio (OR) and 95% confidence intervals (CI). We used Cox regression for evaluation of risk of death.Results. The serum level of angiopoietin-1 was significantly higher in patients with COVID-19 with AKI: 1.8 (1.5; 2.1) ng/ml vs 1.58 (1.29; 1.7) ng/ml in group 2, р &lt; 0.01. In deceased patients, the level of Ang-1 at admission was significantly higher than in patients who was discharged: 1.91 (1.71; 2.32) ng/ml vs 1.58 (1.34; 1.67) ng/ml, respectively, p = 0.0001. In unifactorial regression analysis we confirmed, that increase of serum Ang-1 level &gt;1.66 ng/ml on admission is the risk factor for AKI development in patients with COVID-19 (OR 5.7, 95% CI 1.7–19.1, р &lt; 0.01). In Cox regression development of AKI increased the absolute risk of death: Hazard ratio = 5.159 (95% CI 1.839–14.469), p = 0.002.Conclusion. The high serum level of Ang-1 in patients with COVID-19 at hospital admission is the marker of systemic endothelial dysfunction and the risk factor for AKI and poor prognosis.

Prognostic effects of cardiac rehabilitation in heart failure patients classified according to physical frailty: A propensity score–matched analysis of a nationwide prospective cohort study

BackgroundResearch regarding cardiac rehabilitation (CR) in the prognosis of heart failure (HF) patients and frailty remains lacking. Here, the effects of CR on the 2-year prognosis of HF patients were examined according to their frailty status. MethodsThis multicenter prospective cohort study enrolled patients hospitalized for HF. Patients who underwent ≥1 session per 2 weeks of CR within 3 months after discharge were categorized in the CR group. Patients were divided in a non-frailty (≤8 points) and physical frailty group (≥9 points) based on their FLAGSHIP frailty score. The score is based on HF prognosis, with a higher score indicating worsened physical frailty. A propensity score-matched analysis was performed to compare survival rates between the two groups according to their physical frailty status. Endpoints included HF re-hospitalization and all-cause mortality during a 2-year follow-up period. ResultsOf 2697 patients included in the analysis, 285 and 95 matched pairs were distributed in the non-frailty and physical frailty groups, respectively, after propensity-score matching. CR was associated with lower incidence of HF rehospitalization in both non-frailty (hazard ratio 0.65; 95% confidence interval 0.44–0.96; p = 0.032) and physical frailty (0.54; 0.32–0.90; p = 0.019) groups. CR was not associated with all-cause mortality in either group (log-rank test, p > 0.05). ConclusionThese findings suggest the effects of CR on reduced HF rehospitalization, regardless of physical frailty status.