Useful Predictor Of Clinical Outcome Research Articles

Serum biomarkers related to frailty predict negative outcomes in older adults with hip fracture.

Hip fracture is a public health problem worldwide. Traditional prognostic models do not include blood biomarkers, such as those obtained by proteomics. This study aimed to investigate the relationships between serum inflammatory biomarkers and frailty in older adults with hip fracture as well as adverse outcomes at one and three months after discharge. A total of 45 patients aged 75 or older who were admitted for hip fracture were recruited. At admission, a Comprehensive Geriatric Assessment (CGA) was conducted, which included a frailty assessment using the Clinical Frailty Scale (CFS). Blood samples were collected before surgery. Participants were followed up at one and three months after discharge. The levels of 45 cytokines were analyzed using a high-throughput proteomic approach. Binary logistic regression was used to determine independent associations with outcomes, such as functional recovery, polypharmacy, hospital readmission, and mortality. The results showed that IL-7 (OR 0.66 95% CI 0.46-0.94, p = 0.022) and CXCL-12 (OR 0.97 95% CI 0.95-0.99, p = 0.011) were associated with better functional recovery at three months after discharge, while CXCL-8 (OR 1.07 95% CI 1.01-1.14, p = 0.019) was associated with an increased risk of readmission. These findings suggest that immunology biomarkers may represent useful predictors of clinical outcomes in hip fracture patients.

Apply pressure-strain loop to quantify myocardial work in pulmonary hypertension: A prospective cohort study.

Pressure-strain loop (PSL) is a novel method to quantify myocardial work in many cardiovascular diseases. To investigate the value of myocardial work parameters derived from PSL for evaluating cardiac function and clinical prognosis in patients with pulmonary hypertension (PH). A total of 52 patients with PH and 27 healthy controls were enrolled in this prospective study. PSLs determined by echocardiography were used to calculate global work index (GWI) of left ventricle (LV) and right ventricle (RV). Global constructive work (GCW) comprised the sum of myocardial work performed during shortening in systole and during lengthening in isovolumic relaxation. Global wasted work (GWW) comprised the sum of myocardial work performed during lengthening in systole and during shortening in isovolumic relaxation. Global work efficiency (GWE) was defined as GCW/(GCW + GWW). LVGWW, RVGWI, RVGCW and RVGWW were significantly higher in patients than controls (all P < 0.001). LVGWE, LVGWI, LVGCW, and RVGWE were lower in patients than controls (all P < 0.01). Myocardial work parameters correlated well with clinical and other conventional echocardiographic assessments (all P < 0.05). In binary logistic regression analysis, the combination of RVGWE and estimation of pulmonary arterial systolic pressure (ePASP) was the best model to predict clinical outcomes (OR = 0.803, P = 0.002 and OR = 1.052, P = 0.015, respectively). Receiver operating characteristic curv demonstrated the combination of RVGWE and ePASP was the best predictor of adverse events with 100% sensitivity and 76.3% specificity (AUC = 0.910, P < 0.001). Myocardial work parameters derived from PSL are emerging markers of cardiac function. And the combination of RVGWE and ePASP is a useful predictor of clinical outcome in PH patients.

New-Onset Atrial Fibrillation in Patients With Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease - Insights From the CLAVIS-COVID Registry.

Both pre-existing atrial fibrillation (AF) and new-onset AF (NOAF) are observed in patients with coronavirus disease 2019 (COVID-19); however, the effect of AF on clinical outcomes is unclear. This study aimed to investigate the effect of AF, especially NOAF, on the outcomes of hospitalized patients with COVID-19.Methods and Results: This study analyzed 673 COVID-19 patients with cardiovascular diseases and risk factors (CVDRF). Patients were divided into 3 groups; pre-existing AF (n=55), NOAF (n=28), and sinus rhythm (SR) (n=590). The baseline characteristics and in-hospital outcomes were evaluated. The mean age of the patients was 68 years, 65.4% were male, and the in-hospital mortality rate was 15.6%. The NOAF group demonstrated a higher in-hospital mortality rate (42.9%) than the pre-existing AF (30.9%) and SR (11.2%) groups (P<0.001). Patients with NOAF had a higher incidence of acute respiratory syndrome, multiple organ disease, hemorrhage, and stroke than those with pre-existing AF and NOAF. NOAF was independently associated with in-hospital mortality after adjusting for pre-existing AF and 4C mortality score (odds ratio [95% confidence interval]: 4.71 [1.63-13.6], P<0.001). Patients with NOAF had significantly worse outcomes as compared to patients with pre-existing AF and SR. The incidence of NOAF would be a useful predictor of clinical outcomes during hospitalization.

Thin-slab maximum intensity projection of CT angiography for collateral score and clot burden score evaluation: comparison with conventional CT angiography.

This study aimed to exam the effects of thin-slab maximum intensity projection (TS-MIP) of computed tomography angiography (CTA) for collateral score (CS) and clot burden score (CBS) evaluation in patients with large-vessel-occlusion (LVO) stroke in the anterior circulation. Of 241 consecutive patients with LVO stroke admitted to our center between August 2015 and June 2020, 187 patients were enrolled. CS and CBS were evaluated on conventional CTA and TS-MIP separately. Outcome at 90 days was classified as good if modified Rankin scale (mRS) was ≤2 and as poor if mRS was >2. The correlations between CS and CBS and clinical outcomes were assessed. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic values of CS and CBS. Multivariate logistic regression analysis was performed to identify the independent predictors of 90-day good clinical outcomes. The correlation coefficient for clinical outcomes was significantly better for CS based on TS-MIP than that based on conventional CTA (-0.444 vs. -0.285, P=0.039); no significant difference was found in the CBS evaluation (TS-MIP: -0.356 vs. conventional CTA: -0.320, P=0.348). For predicting good clinical outcomes, TS-MIP-based CS was associated with larger area under the curve (AUC) (0.709 vs. 0.609, P=0.004) and higher sensitivity (69.1% vs. 42.0%, P=0.001) than CS based on CTA. In multivariable logistic regression analysis, the factors independently associated with good outcomes were National Institutes of Health Stroke Scale (NIHSS) score at admission (OR =1.147; P<0.001), TS-MIP-based CS (OR =0.326; P<0.001), final modified treatment in cerebral infarction (mTICI) score of 2b/3 (OR =0.098; P<0.001), and hemorrhagic transformation (OR =3.662; P<0.001). TS-MIP-CTA is superior to conventional CTA for evaluation CS and CBS, and TS-MIP-based CS may be a useful predictor of clinical outcome.

A Longitudinal Study of Semantic Networks in Schizophrenia and other Psychotic Disorders Using the Word Association Task

AbstractThe underpinnings of language deviations in psychotic symptoms (eg, formal thought disorder, delusions) remain unclear. We examined whether the semantic networks underlying word associations are useful predictors of clinical outcomes in psychosis. Fifty-one patients with schizophrenia and other psychotic disorders and 51 matched healthy controls generated words in a Cantonese continued word association task. Patterns of word associations were examined using semantic similarity metrics derived from word embeddings (fastText) and the structure of individual semantic networks. A longitudinal design—baseline and 6 months later—enabled investigation of the relationship of changes in semantic associations in patients who were in an acute psychotic state at baseline compared to clinical stabilization 6 months later. The semantic similarity measure increased over time in patients, while it remained stable in controls. Moreover, the change in semantic similarity over time correlated with the changes in patients’ formal thought disorder symptoms. There were differences in individual semantic networks between the groups at both time points. Patients had less structured networks on average, as evidenced by a smaller network diameter and clustering coefficient, and smaller average shortest path lengths. The identification of several state-like semantic measures that change over time with patients’ mental states allows for nuanced comparison with clinical measures. Semantic measures are complex. Semantic similarity was a state-like measure that changed over time with mental state in psychotic disorders, whereas individual semantic network parameters were trait-like and stable over time.

Abstract 2210: Chromosome arm aneuploidy landscape in lung adenocarcinoma

Abstract Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Overall aneuploidy frequency in LUAD have been previously documented. We aimed to assess whether specific chromosome arm aneuploidy (CAA) patterns can be found in primary tumor and different metastatic sites, and across patients with different driver mutations. We also investigated CAA and driver mutation co-occurrence patterns in LUAD, as well as probable order of CAA acquisition. Methods: We performed targeted panel sequencing (425 cancer-related genes) on 3533 tissue samples from LUAD patients. CAA status (arm gain or loss) was derived from segmental copy number analysis using Sequenza, accounting for purity and ploidy. 4 types of CAA analysis were conducted: total CAA burden, gain-loss pattern, co-occurrence/exclusivity, and population level CAA progression assessed by Tronco on network-based stratified (NBS) subtypes. Results: Use of panel sequencing data for analysis of CAA status was validated against WES results, and achieved high concordance (Kappa: 0.75, Pearson: 0.85). Primary tumor and different metastatic sites had dramatic differences in CAA burdens (p=3.4e-06). Liver and brain had more arm losses than gains compared to primary (q=0.047 and 0.049 respectively). Different driver mutation groups also had significant difference in CAA burden (p&amp;lt;2.2e-16). BRAF group had more arm gains than losses; whereas PIK3CA had more arm losses than gains. TP53 mutation status had a moderating effect on both CAA burden and gain-loss pattern across metastatic sites and driver mutation groups. EGFR 19del and L858R mutations showed significant differences in CAA co-occurrence/exclusion. EGFR 19del tend to co-occur with 4q-, 5p-, 5q-, 8q+, 9p+, 16q+, 17p+, 17q-, 22q-, and was in exclusion with 14q-. EGFR L858R co-occurred with 4q+, but was in exclusion with 1p-, 8p+ and 16p-. MET significantly co-occurred with 1q-, and PIK3CA with 2p+. Clustering of LUAD patients using NBS gave us 2 tight clusters with high silhouette score (0.86). These two LUAD subtypes showed distinct orders of CAA acquisition. Both clustered subtypes began with acquisition of 7p gain. Subtype 1 is dominated by initial arm gains, followed by few arm losses, seen in previously published literature; whereas subtype 2 began with a simultaneous acquisition of 19p loss, with further additions of many arm losses, before eventual accumulation of arm gains. Proportion of these 2 subtypes varied across primary and metastatic sites, and driver mutant groups. Conclusions: There are significant differences in arm aneuploidy patterns across metastatic sites and mutation groups. Overall, LUAD patients exhibit a unique pattern of co-occurrence and exclusivity between CAA and driver mutations, as well as two subtypes with distinct CAA evolution trajectories. These CAA patterns may hold biological meaning and may be useful predictors of clinical outcomes and warrants further investigation. Citation Format: Hua Bao, Ming Han, Yi Shen, Xue Wu, Yang Shao. Chromosome arm aneuploidy landscape in lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2210.

Impact of right atrial structural remodeling on recurrence after ablation for atrial fibrillation.

BackgroundRecurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) is associated with left atrial (LA) remodeling; however, its association with right atrial (RA) remodeling remains unclear.ObjectiveThis study aimed to identify whether RA structural remodeling could predict recurrence of AF after PVI.MethodsThis study prospectively analyzed 245 patients with AF who had undergone PVI. RA and LA volumes were determined by contrast‐enhanced computed tomography. Atrial structural remodeling was defined as an atrial volume of ≥110 mL according to previous reports and receiver operating characteristic curve analysis.ResultsAfter excluding 32 patients, 213 patients were analyzed. During a follow‐up period of 12 months, 41 patients (19%) demonstrated atrial arrhythmia recurrence after PVI. With the Cox proportional‐hazards model, RA structural remodeling was the only predictor of arrhythmia recurrence (hazard ratio, 1.012; 95% confidence interval 1.003‐1.021; P = .009). Kaplan–Meier analysis showed that arrhythmia recurrence was more frequent in the RA structural remodeling group compared with the group without RA remodeling (log‐rank, P < .001), and the arrhythmia‐free survival rates in these groups at 12 months were 68.0% and 91.4%, respectively. Additionally, there was a significant difference in recurrence‐free survival after RA structural remodeling in each type of AF (log‐rank, P < .001).ConclusionsRA structural remodeling is a useful predictor of clinical outcome after PVI regardless of the type of AF. Our results suggest that patients without RA structural remodeling may be good candidates for successful ablation with PVI.

Spatiotemporal Heterogeneity in Multiparametric Physiologic MRI Is Associated with Patient Outcomes in IDH-Wildtype Glioblastoma.

Heterogeneity in glioblastomas is associated with poorer outcomes, and physiologic heterogeneity can be quantified with noninvasive imaging. We developed spatial habitats based on multiparametric physiologic MRI and evaluated associations between temporal changes in these habitats and progression-free survival (PFS) after concurrent chemoradiotherapy (CCRT) in patients with glioblastoma. Ninety-seven patients with isocitrate dehydrogenase (IDH)-wildtype glioblastoma were enrolled and two serial MRI examinations after CCRT were analyzed. Cerebral blood volumes and apparent diffusion coefficients were grouped using k-means clustering into three spatial habitats. Associations between temporal changes in spatial habitats and PFS were investigated using Cox proportional hazard modeling. The performance of significant predictors for PFS and overall survival (OS) was measured using a discrete increase of habitat (habitat risk score) in a temporal validation set from a prospective registry (n = 53, ClinicalTrials.gov NCT02619890). The site of progression was matched with the spatiotemporal habitats. Three spatial habitats of hypervascular cellular, hypovascular cellular, and nonviable tissue were identified. A short-term increase in the hypervascular cellular habitat (HR, 40.0; P = 0.001) and hypovascular cellular habitat was significantly associated with shorter PFS (HR, 3.78; P < 0.001) after CCRT. Combined with clinical predictors, the habitat risk score showed a C-index of 0.79 for PFS and 0.74 for OS and stratified patients with short, intermediate, and long PFS (P = 0.016). An increase in the hypovascular cellular habitat predicted tumor progression sites. Hypovascular cellular habitats derived from multiparametric physiologic MRIs may be useful predictors of clinical outcomes in patients with posttreatment glioblastoma.

Elevated admission lactate levels in the emergency department are associated with increased 30-day mortality in non-trauma critically ill patients

BackgroundElevated blood lactate levels were reported as useful predictors of clinical outcome and mortality in critically ill patients. To identify higher-risk patients, this investigation evaluated the relationship between patient mortality and admission lactate levels during the management of non-trauma critically ill patients in the emergency department (ED).MethodsIn this prospective, single centre observational study in a German university ED, all adult patients who were admitted to the ED resuscitation room were evaluated between September 1, 2014 and August 31, 2015. Blood samples for blood gas analysis, including lactate levels, were obtained immediately at admission. Study endpoint was 30-day mortality.ResultsDuring the study period, 532 patients were admitted to the resuscitation room of the ED. The data of 523 patients (98.3%) were available. The overall 30-day mortality was 34.2%. Patients presenting to the resuscitation room with admission lactate levels < 2.0 mmol/l had a 30-day mortality of 22.7%, while admission lactate levels above 8.0 mmol/l were associated with higher mortality (8.0–9.9 mmol/l: OR: 2.83, 95%CI: 1.13–7.11, p = 0.03, and ≥ 10 mmol/l: OR: 7.56, 95%CI: 4.18–13.77, p < 0.001).ConclusionHigh lactate levels at admission are associated with an increased 24-h and 30-day mortality. These measurements may be used not only to predict mortality, but to help identify patients at risk for becoming critically ill. The breakpoint for mortality may be an ALL ≥8.0 mmol/l.

C-reactive Protein Levels Predict Right Ventricular Failure and Mortality in Patients Undergoing Continuous-Flow Left Ventricular Assist Device Assist Device Implantation: An INTERMACS Analysis

Whether C-reactive protein (CRP) levels prior to left ventricular assist device implantation (LVAD) are predictive of post-implantation outcomes is not well established. Current data are limited to small, single-center studies. 5,183 adult recipients of continuous-flow left ventricular assist devices with pre-implant CRP measurement were identified from INTERMACS. Patients were divided into three groups based on pre-implant CRP levels: CRP of 0 to 10 mg/L (low), 11 to 30 mg/L (intermediate), and >30 mg/L (high). Outcomes of interest were mortality, gastrointestinal bleeding, device thrombosis, infection, stroke, and right heart failure. Analyses included Kaplan-Meier survival estimates and Cox proportional hazards models. Patients with higher pre-implant CRP were younger (55.3 vs 56.5 vs 57.8 yrs), had sicker INTERMACS profiles (Class I: 33.7% vs 22.6% vs 9.5%); higher use of IABP (34.1% vs 26.0% vs 14.5%) and ECMO (12.0% vs 6.9% vs 2.1%) compared to patients with intermediate and low CRP levels (all p <0.001). High CRP group had higher WBC count (10.4 vs 9.3 vs 8.0 × 10/uL), total bilirubin (1.6 vs 1.4 vs 1.2 mg/dL), and serum BNP levels (958 vs 887 vs 726 pg/mL) compared to lower CRP groups (all p<0.001). After adjustment for baseline characteristics, compared to the low CRP group, higher CRP was associated with greater risk of mortality (HR 1.14 for intermediate CRP, HR 1.29 for high CRP, p=0.006) and right heart failure (HR 0.91 for intermediate CRP, HR 1.41 for high CRP, p=0.004). Rates of device thrombosis, device-related infection, stroke, and gastrointestinal bleeding were similar across groups. Higher CRP levels indicate comorbidity prior to LVAD implantation and predict higher risk of post-implant right heart failure and mortality. These findings suggest that baseline CRP may be a useful predictor of clinical outcome after LVAD implantation.

Long Noncoding RNA NEAT1 Upregulates Survivin and Facilitates Gallbladder Cancer Progression by Sponging microRNA-335.

BackgroundGallbladder cancer (GBC) is the most common cancer of the biliary tract, but molecularly targeted therapies are not available for GBC. Loss of microRNA (miR)-335 expression may be a useful predictor of clinical outcomes and the reversal of its loss of expression may be a useful treatment strategy for GBC. In this study, we investigated whether a long noncoding RNA, nuclear paraspeckle assembly transcript 1 (NEAT1) sponges miR-335 in GBC cells.Materials and MethodsQuantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were used to determine the expression of miR-335; NEAT1; survivin; and Ki67 in GBC cell lines (GBC-SD and SGC-996) and tissue samples from patients (n = 25). Cell Counting Kit-8, colony-formation, and Transwell migration and invasion assays were performed to measure cell proliferation, migration, and invasion. Bioinformatic analysis and dual-luciferase reporter assays were utilized to analyze correlativity.ResultsmiR-335 overexpression resulted in inhibition of GBC cell proliferation and invasion. In addition, knockdown of NEAT1 resulted in downregulation of survivin expression. As NEAT1 competitively “sponges” miR-335, NEAT1 knockdown resulted in inhibited GBC cell proliferation and invasion in vitro and GBC tumor growth in vivo. Furthermore, NEAT1 was found to be upregulated in GBC samples, and its expression was inversely correlated with miR-335 levels, but positively correlated with survivin levels.ConclusionThese findings indicate that NEAT1 promotes survivin expression by functioning as a competitive endogenous RNA for miR-335 in GBC cells; thus, we have identified a potential biomarker and target for GBC diagnosis and therapy.

Prognostic value of miR-221 in human malignancy: evidence from 3041 subjects

BackgroundMiR-221, acting as onco-miR or oncosuppressor-miR, plays an important role in tumor progression; however, the prognostic value of miR-221 in human carcinomas is controversial and inconclusive. The objective of our study was to conducted a systematic review and meta-analysis of miR-221 in various types of human cancers.MethodsAn online search of up-to-date electronic databases, including PubMed and Embase, was conducted to identify as many relevant papers as possible. 32 papers involving 3041 patients with different carcinomas were included in the analysis. Hazard ratios (HRs) of miR-221 were used to evaluate prognostic values.ResultsThirty-two papers involving 15 cancers were included. MiR-221 was associated with a worse overall survival (OS) in patients, and a combined HR was 1.93 (95% CI of 1.43–2.60, 2080 patients, 22 studies, I-squared = 80.4%, P = 0.000); however, the combined HR for relapse-free survival (RFS) was 1.37 (95% CI of 0.75–2.48, 625 patients, 7 studies, I-squared = 78.8%, P = 0.000), and disease-free survival (DFS) was 1.24 (95% CI of 0.60–2.56, 539 patients, 5 studies, I-squared = 81.8%, P = 0.000).ConclusionMiR-221 was shown to be associated with a poor OS in human carcinomas, and thus may serve as a useful predictor of clinical outcomes.

FKBP5 rs4713916: A Potential Genetic Predictor of Interindividual Different Response to Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease in a Real-Life Setting.

Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable lung disease characterized by large heterogeneity in disease presentation and grades impairment. Inhaled corticosteroids (ICS) are commonly used to manage COPD/COPD-exacerbation. The patient’s response is characterized by interindividual variability without disease progression/survival modification. Objectives: We hypothesize that a therapeutic intervention may be more effective if single nucleotide polymorphisms (SNPs) are investigated. Methods: In 71 COPD patients under pulmonary rehabilitation, a small number of powerful SNPs, selected according to current literature, were analyzed; namely the glucocorticoid receptor gene NR3C1 (rs6190/rs6189/rs41423247), the glucocorticoid-induced transcript 1 gene (GLCCI1 rs37972), and the related co-chaperone FKBP5 gene (rs4713916). MDR1 rs2032582 was also evaluated. Lung function outcomes were assessed. Results: A significant association with functional outcomes, namely FEV1 (forced expiration volume/one second) and 6MWD (six-minutes walking distance), was found for rs4713916 and weakly for rs37972. The genotype rs4713916(GA) and, in a lesser extent, the genotype rs37972(TT), were more favorable than the wild-type. Conclusions: Our study supports a possible picture of pharmacogenomic control for COPD intervention. rs4713916 and, possibly, rs37972 may be useful predictors of clinical outcome. These results may help to tailor an optimal dose for individual COPD patients based on their genetic makeup.

Non‐Val30Met mutation, septal hypertrophy, and cardiac denervation in patients with mutant transthyretin amyloidosis

AimsMutant transthyretin (ATTRm) amyloidosis is a systemic disease caused by the deposition of amyloid fibrils derived from mutated transthyretin. Although cardiac involvement impacts the prognosis of patients with ATTRm amyloidosis, the incidence of cardiac events, such as bradyarrhythmia, ventricular tachycardia, and heart failure, has not been fully elucidated. The aim of this study was to evaluate the prognosis and predictors of clinical outcomes, including cardiac events, in patients with ATTRm amyloidosis in Japan.Methods and resultsWe evaluated 90 consecutive patients with ATTRm amyloidosis at Kumamoto University. ATTRm amyloidosis was diagnosed by the observation of both amyloid fibril deposition on tissue biopsy and a transthyretin mutation on sequential analysis. Sympathetic nerve activity was evaluated in 59 patients using 123‐iodine metaiodobenzylguanidine (123I‐MIBG) imaging. The endpoint was a composite of all‐cause death, hospitalization for heart failure, and implantation of a pacemaker, implantable cardioverter defibrillator, or cardiac resynchronization therapy defibrillator. Sixty‐seven patients had the Val30Met mutation (74%). The composite endpoint occurred in 23 patients (26%): all‐cause death (n = 6), hospitalization for worsening heart failure (n = 1), and implantation of an implantable cardioverter defibrillator (n = 6), cardiac resynchronization therapy defibrillator (n = 3), or pacemaker (n = 7). The 5‐year incident rate for clinical outcomes was 19%. In a multivariate Cox hazard analysis, age [hazard ratio (HR): 1.07, 95% confidence interval (95% CI): 1.01–1.12, P = 0.015], PQ interval (HR: 1.01, 95% CI: 1.00–1.02, P = 0.042), interventricular septum thickness in diastole (HR: 1.25, 95% CI: 1.09–1.42, P = 0.001), and non‐Val30Met mutation (HR: 4.31, 95% CI: 1.53–12.16, P = 0.006) were independent predictive factors of clinical outcomes. Kaplan–Meier analysis demonstrated a significantly higher probability of the composite endpoint in the non‐Val30Met group than in the Val30Met group (log‐rank test: P = 0.002) and in patients with left ventricular hypertrophy than in patients without left ventricular hypertrophy (log‐rank test: P < 0.001). In patients who underwent 123I‐MIBG imaging, a delayed heart‐to‐mediastinum (HM) ratio <1.6 was a significant predictive factor of the composite endpoint (HR: 4.98, 95% CI: 1.73–14.37, P = 0.003) in the univariate Cox hazard analyses. Kaplan–Meier curve analysis showed that a delayed HM ratio <1.6 was associated with a poor prognosis (log‐rank test: P = 0.001).ConclusionsNon‐Val30Met mutation, septal hypertrophy, and a delayed HM ratio are useful predictors of clinical outcomes in patients with ATTRm amyloidosis in Japan. These results suggest that it is important to evaluate cardiac involvement in terms of morphological (left ventricular hypertrophy) and functional (cardiac denervation) perspectives using echocardiography and 123I‐MIBG imaging, respectively.

Polypharmacy and Unplanned Hospitalizations in Patients with Rheumatoid Arthritis.

Polypharmacy (PP), the prescribing of multiple drugs for an individual, is rising in prevalence. PP associates with an increased risk of adverse drug reactions (ADR) and hospital admissions. We investigated the relationship between PP, characteristics of rheumatoid arthritis (RA), and the risk of unplanned hospital admissions. Patients from a hospital RA cohort were retrospectively analyzed. Information was collected from electronic medical records. Cox proportional hazards were used to compare hospitalization risk according to levels of PP. Admissions were adjudicated to determine whether an ADR was implicated. The study included 1101 patients; the mean number of all medications was 5. PP correlated with increasing age, disease duration, disease activity, and disability. At least 1 unplanned admission occurred for 16% of patients. Patients taking ≥ 10 medications had an adjusted HR for hospitalization of 3.1 (95% CI 2.1-4.5), compared to those taking 0-5 medications. Corticosteroid use associated with a doubling in adjusted risk of admission of 1.7 (95% CI 1.2-2.4). The most common reason for hospitalization was infection (28%). While in half of all admissions an ADR was a possible contributing factor, only 2% of admissions were found to directly result from an ADR. PP is common in RA and is a prognostic marker associated with increased risk of acute hospitalizations. Our data suggest that PP may be an indicator of comorbidity burden rather than a contributing cause of a drug-related toxicity. PP should be monitored to minimize inappropriate combination of prescribed medications. PP may be a useful predictor of clinical outcomes in epidemiologic studies.

The Hopelessness Theory of Depression: Clinical Utility and Generalizability

To date, “basic” research has dominated the empirical literature on hopelessness theory. The next logical step in this area of research is to determine if the theory can be used to help people. We conducted three studies to determine if the cognitive vulnerability factor featured in hopelessness theory could be reliably measured in diverse samples in a treatment context and if it could predict depressive therapeutic outcomes. Study 1 used a sample of male juvenile detainees (n = 296; 70% from underrepresented groups) and found that cognitive vulnerability moderated the effectiveness of a social problem solving training intervention. Study 2 used a clinical sample of U.S. Veterans (n = 16; 56% from underrepresented groups) enrolled in a cognitive behavioral therapy group for depression and found that cognitive vulnerability predicted post-therapy depressive outcomes. In both Study 1 and Study 2, higher levels of cognitive vulnerability resulted in poorer treatment outcomes (i.e., greater post-treatment levels of depressive symptoms). Study 3 used a clinical sample of U.S. Veterans (n = 76; 67% from underrepresented groups) enrolled in a behavior activation group and found no effect of cognitive vulnerability on post-therapy depressive outcomes. The results of the three studies indicate that hopelessness theory’s cognitive vulnerability construct can be reliably measured in diverse samples in real world clinical contexts and that it has the potential to be a useful predictor of clinical outcomes in the context of cognitively focused treatments.

The Right to Left Atrial Volume Ratio Predicts Outcomes after Circumferential Pulmonary Vein Isolation of Longstanding Persistent Atrial Fibrillation.

We aimed to identify the predictors of clinical outcomes after circumferential pulmonary vein isolation (CPVI) without any substrate modification for longstanding persistent atrial fibrillation (LSP-AF). This study retrospectively analyzed 70 consecutive LSP-AF patients who underwent an initial CPVI and were followed-up for more than 1 year. The right and left atrial volumes indexed to the body surface areas (right atrial volume index [RAVI] and left atrial volume index [LAVI]) were determined by preacquired contrast-enhanced computed tomography (CT). The %RAVI/LAVI was obtained as 100 × RAVI/LAVI. During a median follow-up period of 15 months (interquartile range, 13-19 months), 21 patients (30%) had arrhythmia recurrences after the CPVI. Antiarrhythmic drugs were continued in 34 patients (48%). In the Cox proportional hazard model, the %RAVI/LAVI was a significant positive predictor of arrhythmia recurrences (hazard ratio, 1.048; P = 0.039). A receiver-operating characteristic analysis demonstrated that at an optimal cutoff of 100.1 for the %RAVI/LAVI, the sensitivity and specificity for predicting arrhythmia recurrences were 85.7% and 71.4%, respectively. The Kaplan-Meier analysis showed that arrhythmia recurrences were less frequent in patients with a %RAVI/LAVI of <100.1 than in those with a %RAVI/LAVI of ≥100.1 (P < 0.0001), and the arrhythmia-free survival rate at 12 months was 89.7% and 45.2%, respectively. The ratio of the RAVI to LAVI on CT may be a useful predictor of clinical outcomes after CPVI of LSP-AF. LSP-AF patients with a less predominant right atrial enlargement relative to the left atrial enlargement may be good candidates for successful treatment with CPVI alone as the ablation strategy for LSP-AF.

Serum lactate level as a useful predictor of clinical outcome after surgery: an unfulfilled potential?

Serum lactate level as a useful predictor of clinical outcome after surgery: an unfulfilled potential?

Influences of ERCC1, ERCC2, XRCC1, GSTP1, GSTT1, and MTHFR polymorphisms on clinical outcomes in gastric cancer patients treated with EOF chemotherapy.

This study investigated the associations between genetic polymorphisms of six genes involved in DNA repair, detoxification pathways, and fluoropyrimidine metabolism and clinical outcomes in MGC patients receiving EOF treatment. This retrospective study included 108 Chinese MGC patients receiving EOF as first-line chemotherapy. Nine single nucleotide polymorphisms (SNPs) of six genes (ERCC1 rs2298881, ERCC2 rs13181 and rs1799793, XRCC1 rs25487 and rs25489, GSTP1 rs1695, GSTT1 rs2266637, and MTHFR rs1801133 and rs1801131) were genotyped, and the associations between each SNP and clinical outcome were analyzed. XRCC1 rs25487 A allele was significantly associated with progression disease (PD) to EOF (p = 0.002), and patients with AA genotype had significantly poorer progression-free survival (PFS) (p = 0.001) and overall survival (OS) (p = 0.041) compared with patients with the G allele (GG + GA). ERCC2 rs13181 G allele was significantly associated with PD (p = 0.026), and G carriers (GG + GT) tended to have poorer PFS (p = 0.092) than TT homozygotes. ERCC2 rs1799793 GA genotype was associated with unfavorable PFS (p = 0.034) and a tendency toward poorer OS (p = 0.090) compared with GG homozygotes. Patients were categorized as either good (0 risk factors) or poor risk (≥1 unfavorable SNPs) using a prognostic index based on XRCC1 rs25487 AA, ERCC2 rs13181 (GG + GT), and ERCC2 rs1799793 GA genotypes, with median OS and PFS of 534days, 281days (p = 0.009) and 206days, and 123days (p < 0.001), respectively. These results suggest that the prognostic index comprising XRCC1 rs25487, ERCC2 rs13181, and rs1799793 polymorphisms may be a useful predictor of clinical outcomes in MGC treated with EOF.

Propensity Score Matching Analysis of Changes in Alpha-Fetoprotein Levels after Combined Radiotherapy and Transarterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

Background and AimTo investigate the value of changes in alpha-fetoprotein (AFP) levels for the prediction of radiologic response and survival outcomes in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) who received combined treatment of 3-dimensional conformal radiotherapy (3D-CRT) and transarterial chemoembolization (TACE).MethodsA database of 154 HCC patients with PVTT and elevated AFP levels (>20 ng/mL) treated with 3D-CRT and TACE as an initial treatment between August 2002 and August 2008 was retrospectively reviewed. AFP levels were determined 1 month after radiotherapy, and AFP response was defined as an AFP level reduction of >20% from the initial level. Radiologic response, overall survival (OS), and progression-free survival (PFS) rates were compared between AFP responders and non-responders. Propensity-score based matching analysis was performed to minimize the effect of potential confounding bias.ResultsThe median follow-up period was 11.1 months (range, 3.1–82.7 months). In the propensity-score matching cohort (92 pairs), a best radiologic response of CR or PR occurred in more AFP responders than AFP non-responders (41.3% vs. 10.9%, p < 0.001). OS and PFS were also longer in AFP responders than in non-responders (median OS 13.2 months vs. 5.6 months, p < 0.001; median PFS 8.7 months vs. 3.5 months, p < 0.001).ConclusionsAFP response is a significant predictive factor for radiologic response. Furthermore, AFP response is significant for OS and PFS outcomes. AFP evaluation after combined radiotherapy and TACE appears to be a useful predictor of clinical outcomes in HCC patients with PVTT.