scholarly journals Pretreatment Plasma IL-6 and YKL-40 and Overall Survival after Surgery for Metastatic Bone Disease of the Extremities

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2833
Author(s):  
Michala Skovlund Sørensen ◽  
Thomas Colding-Rasmussen ◽  
Peter Frederik Horstmann ◽  
Klaus Hindsø ◽  
Christian Dehlendorff ◽  
...  
Keyword(s):  
Bone Disease ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Continuous Variable ◽  
Metastatic Bone Disease ◽  
Cox Regression Analysis ◽  
Tertiary Referral Center ◽  
A Prospective Study ◽  
Risk Factors For Survival

Background: Plasma IL-6 and YKL-40 are prognostic biomarkers for OS in patients with different types of solid tumors, but they have not been studied in patients before surgery of metastatic bone disease (MBD) of the extremities. The aim was to evaluate the prognostic value of plasma IL-6 and YKL-40 in patients undergoing surgery for MBD of the extremities. Patients and Methods: A prospective study included all patients undergoing surgery for MBD in the extremities at a tertiary referral center during the period 2014–2018. Preoperative blood samples from index surgery were included. IL-6 and YKL-40 concentrations in plasma were determined by commercial ELISA. A total of 232 patients (median age 66 years, IQR 58–74; female 51%) were included. Results: Cox regression analysis was performed to identify independent prognostic factors for OS. IL-6 correlated with YKL-40 (rho = 0.46, p < 0.01). In univariate analysis (log2 continuous variable) IL-6 (HR = 1.26, 95% CI 1.16–1.37), CRP (HR = 1.20, 95% CI 1.12–1.29) and YKL-40 (HR = 1.25, 95% CI 1.15–1.37) were associated with short OS. In multivariable analysis, adjusted for known risk factors for survival, only log2(IL-6) was independently associated with OS (HR = 1.24, 95% CI 1.08–1.43), whereas CRP and YKL-40 were not. Conclusion: High preoperative plasma IL-6 is an independent biomarker of short OS in patients undergoing surgery for MBD.

scholarly journals Intra-Aortic Balloon Pump Bridging to Heart Transplantation

2020 ◽  
Vol 13 (8) ◽  
Author(s):  
Lauren V. Huckaby ◽  
Laura M. Seese ◽  
Michael A. Mathier ◽  
Gavin W. Hickey ◽  
Arman Kilic
Keyword(s):  
Heart Transplantation ◽  
Policy Change ◽  
Odds Ratio ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Cox Regression Analysis ◽  
Post Transplant ◽  
Baseline Characteristics ◽  
The Impact

Background: This study evaluates the impact of the 2018 allocation policy change on outcomes of orthotopic heart transplantation (OHT) in patients bridged with intra-aortic balloon pumps (IABPs). Methods: Adult (≥18 years) patients undergoing OHT between 2013 and 2019 who were bridged with an IABP were stratified based on temporal relation to the policy change. Univariate analysis was used to compare baseline characteristics and postoperative outcomes. Multivariate Cox regression analysis was used to estimate risk-adjusted predictors of post-transplant mortality. Results: A total of 1342 (8.6%) OHT patients were bridged with an IABP during the study period. Rates of bridging with IABP to OHT increased significantly after the policy change (7.0% versus 24.9%, P <0.001). The mean recipient age was 54.1±12.1 years with 981 (73.1%) patients being male. Baseline characteristics were similar between the 2 groups whereas post–policy change patients spent fewer days on the waitlist (15 versus 35 days, P <0.001), had longer ischemic times (3.5 versus 3.0 hours, P <0.001), and received organs from a greater distance (301 versus 105 miles, P <0.001). By multivariable analysis, days on the waitlist (for every 30 days; odds ratio, 1.01 [95% CI, 1.00–1.02], P =0.031) and diabetes mellitus (odds ratio, 1.87 [95% CI, 1.16–3.02], P =0.011) emerged as significant predictors of post-transplant mortality. After the policy change, waitlisted patients requiring IABP support were more likely to survive to transplant (76.4 versus 89.8%, P <0.001). Conclusions: IABP utilization has increased over 3-fold since the 2018 policy change with improved waitlist outcomes and comparable post-OHT survival. Thus, bridging patients to OHT with IABPs appears to be an effective strategy in the current era.

Development of a scoring system for survival following surgery for metastatic bone disease

2021 ◽  
Vol 103-B (11) ◽  
pp. 1725-1730
Author(s):  
Rachel Baumber ◽  
Craig Gerrand ◽  
Michael Cooper ◽  
William Aston
Keyword(s):  
Survival Time ◽  
Bone Disease ◽  
Scoring System ◽  
Surgical Intervention ◽  
Cox Regression ◽  
White Cell Count ◽  
Physiological State ◽  
Multivariable Analysis ◽  
Metastatic Bone Disease ◽  
Number Of Patients

Aims The incidence of bone metastases is between 20% to 75% depending on the type of cancer. As treatment improves, the number of patients who need surgical intervention is increasing. Identifying patients with a shorter life expectancy would allow surgical intervention with more durable reconstructions to be targeted to those most likely to benefit. While previous scoring systems have focused on surgical and oncological factors, there is a need to consider comorbidities and the physiological state of the patient, as these will also affect outcome. The primary aim of this study was to create a scoring system to estimate survival time in patients with bony metastases and to determine which factors may adversely affect this. Methods This was a retrospective study which included all patients who had presented for surgery with metastatic bone disease. The data collected included patient, surgical, and oncological variables. Univariable and multivariable analysis identified which factors were associated with a survival time of less than six months and less than one year. A model to predict survival based on these factors was developed using Cox regression. Results A total of 164 patients were included with a median survival time of 1.6 years (interquartile range 0.5 to 3.1) after surgery. On multivariable analysis, a higher American Society of Anesthesiologists grade (p < 0.001), a high white cell count (p = 0.002), hyponatraemia (p = 0.001), a preoperative resting heart rate of > 100 bpm (p = 0.052), and the type of primary cancer (p = 0.026) remained significant predictors of reduced survival time. The predictive model developed showed good discrimination and calibration to predict both six- and 12-month survival in patients with metastatic bone disease. Conclusion In addition to surgical and oncological factors, the level of comorbidity and physiological state of the patient has a significant impact on survival in patients with metastatic bone disease. These factors should be considered when assessing the appropriateness of surgical intervention. This is the first study to examine other patient factors alongside surgical and oncological data to identify a relationship between these and survival. Cite this article: Bone Joint J 2021;103-B(11):1725–1730.

scholarly journals Identification of prognostic alternative splicing events in sarcoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hongshuai Li ◽  
Jie Yang ◽  
Guohui Yang ◽  
Jia Ren ◽  
Yu Meng ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Area Under The Curve ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Functional Roles ◽  
Cancer Pathogenesis ◽  
Rare Malignancy

AbstractSarcoma is a rare malignancy with unfavorable prognoses. Accumulating evidence indicates that aberrant alternative splicing (AS) events are generally involved in cancer pathogenesis. The aim of this study was to identify the prognostic value of AS-related survival genes as potential biomarkers, and highlight the functional roles of AS events in sarcoma. RNA-sequencing and AS-event datasets were downloaded from The Cancer Genome Atlas (TCGA) sarcoma cohort and TCGA SpliceSeq, respectively. Survival-related AS events were further assessed using a univariate analysis. A multivariate Cox regression analysis was also performed to establish a survival-gene signature to predict patient survival, and the area-under-the-curve method was used to evaluate prognostic reliability. KOBAS 3.0 and Cytoscape were used to functionally annotate AS-related genes and to assess their network interactions. We detected 9674 AS events in 40,184 genes from 236 sarcoma samples, and the 15 most significant genes were then used to construct a survival regression model. We further validated the involvement of ten potential survival-related genes (TUBB3, TRIM69, ZNFX1, VAV1, KCNN2, VGLL3, AK7, ARMC4, LRRC1, and CRIP1) in the occurrence and development of sarcoma. Multivariate survival model analyses were also performed, and validated that a model using these ten genes provided good classifications for predicting patient outcomes. The present study has increased our understanding of AS events in sarcoma, and the gene-based model using AS-related events may serve as a potential predictor to determine the survival of sarcoma patients.

scholarly journals Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

2016 ◽  
Vol 397 (12) ◽  
pp. 1265-1276 ◽  
Author(s):  
Nancy Ahmed ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Enken Drecoll ◽  
Matthias Kotzsch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Residual Tumor ◽  
Mrna Levels ◽  
Serous Ovarian Cancer ◽  
Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

scholarly journals Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5824-5831 ◽  
Author(s):  
Ana Flávia Tibúrcio Ribeiro ◽  
Marta Pratcorona ◽  
Claudia Erpelinck-Verschueren ◽  
Veronika Rockova ◽  
Mathijs Sanders ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Gene Expression Signature ◽  
Mutation Status ◽  
Cox Regression Analysis ◽  
Prognostic Effect ◽  
Or Gene ◽  
Acute Myeloid

Abstract The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that patients with DNMT3Amutant AML show significantly worse overall survival (OS; P = .022; hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.04-1.81), and relapse-free survival (RFS; P = .005; HR, 1.52; 95% CI, 1.13-2.05) than DNMT3Awild-type AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavorable prognostic value for OS (P = .003; HR, 1.82; 95% CI, 1.2-2.7) and RFS (P < .001; HR, 2.2; 95% CI, 1.4-3.3). In a composite genotypic subset of cytogenetic intermediate-risk AML without FLT3-ITD and NPM1 mutations, this association is particularly evident (OS: P = .013; HR, 2.09; 95% CI, 1.16-3.77; RFS: P = .001; HR, 2.65; 95% CI, 1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, because DNMT3Amutant AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3Awild-type AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.

scholarly journals Endobronchial Therapy With Gentamicin and Dexamethasone After Airway Clearance by Bronchoscopy in Exacerbation of Non-Cystic Fibrosis Bronchiectasis: A Real-World Observational Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiuhong Li ◽  
Beijie Huang ◽  
Hongyan Gu ◽  
Ying Zhou ◽  
Xizheng Shan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Intratracheal Instillation ◽  
Drug Group ◽  
Control Group ◽  
Cox Regression Analysis ◽  
Airway Clearance ◽  
Significant Prolongation

Background: The exacerbation of non-cystic fibrosis bronchiectasis (NCFB) may lead to poor prognosis. The objective of this study was to retrospectively analyze the clinical efficacy and safety of endobronchial therapy with gentamicin and dexamethasone after airway clearance by bronchoscopy in the exacerbation of NCFB.Methods: We retrospectively reviewed 2,156 patients with NCFB between January 2015 and June 2016 and 367 consecutive patients with exacerbation of bronchiectasis who had complete data and underwent airway clearance (AC) by bronchoscopy. The final cohort included 181 cases of intratracheal instillation with gentamicin and dexamethasone after AC (a group with airway drugs named the drug group) and 186 cases of AC only (a group without airway drugs named the control group). The last follow-up was on June 30, 2017.Results: The total cough score and the total symptom score in the drug group were improved compared to those in the control group during 3 months after discharge (p &lt; 0.001). Re-examination of chest HRCT within 4–6 months after discharge revealed that the improvements of peribronchial thickening, the extent of mucous plugging, and the Bhalla score were all significantly improved in the drug group. Moreover, the re-exacerbations in the drug group were significantly decreased within 1 year after discharge. Univariate analysis showed a highly significant prolongation of the time to first re-exacerbation in bronchiectasis due to treatment with airway drugs compared with that of the control group. Multivariate Cox regression analysis showed that the risk of first re-exacerbation in the drug group decreased by 29.7% compared with that of the control group.Conclusion: Endobronchial therapy with gentamicin and dexamethasone after AC by bronchoscopy is a safe and effective method for treating NCFB.

scholarly journals Construction and Validation of a Prognostic Risk Model Based on Autophagy-Related Genes in Hepatocellular Carcinoma Cells

2021 ◽  
Author(s):  
Rui Feng ◽  
Jian Li ◽  
Weiling Xuan ◽  
Hanbo Liu ◽  
Dexin Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Differential Expression ◽  
Prognostic Model ◽  
Risk Model ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Differential Expression Analysis ◽  
Cox Regression Analysis ◽  
Dismal Prognosis

Abstract Background Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer and the main cause of cancer mortality. Its high complexity and dismal prognosis bring dramatic difficulty to treatment. Due to the disclosed dual functions of autophagy in cancer development, understanding autophagy-related genes devotes into seeking novel biomarkers for HCC. Methods Differential expression of genes in normal and tumor groups was analyzed to acquire autophagy-related genes in HCC. GO and KEGG pathway analyses were conducted on these genes. Genes were then screened by univariate regression analysis. The screened genes were subjected to multivariate Cox regression analysis to build a prognostic model. The model was validated by ICGC validation set. Results Altogether, 42 autophagy-related differential genes were screened by differential expression analysis. Enrichment analysis showed that they were mainly enriched in pathways including regulation of autophagy and cell apoptosis. Genes were screened by univariate analysis and multivariate Cox regression analysis to build a prognostic model. The model was constituted by 6 feature genes: EIF2S1, BIRC5, SQSTM1, ATG7, HDAC1, FKBP1A. Validation confirmed the accuracy and independence of this model in predicting HCC patient’s prognosis. Conclusion A total of 6 feature genes were identified to build a prognostic risk model. This model is conducive to investigating interplay between autophagy-related genes and HCC prognosis.

scholarly journals Association of methicillin resistance with mortality of hospital-acquired Staphylococcus aureus bacteremia

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110588
Author(s):  
Tomonori Aratani ◽  
Hitoshi Tsukamoto ◽  
Takashi Higashi ◽  
Takaaki Kodawara ◽  
Ryoichi Yano ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Regression Analysis ◽  
Cox Regression ◽  
Methicillin Resistance ◽  
Univariate Analysis ◽  
Cox Regression Analysis ◽  
Staphylococcus Aureus Bacteremia ◽  
Mortality Outcome ◽  
Delayed Initiation ◽  
Hospital Acquired

Objective Methicillin-resistant (MR) Staphylococcus aureus bacteremia (SAB) is associated with higher mortality rates than methicillin-susceptible (MS) SAB. This study assessed potential predictors of mortality and evaluated the association of methicillin resistance with mortality in patients with SAB. Methods We conducted a retrospective cohort study in patients with hospital-acquired SAB, from 2009 to 2018. Clinical features of patients with MR-SAB were compared with those of patients with MS-SAB and predictors of 30-day mortality were determined using Cox regression analysis. Results Among 162 patients, 56.8% had MR-SAB. Overall 30-day mortality was 19.1%; MR-SAB had higher mortality (25.0%) than MS-SAB (11.4%). Univariate analysis highlighted long-term hospitalization, prior antibiotics use, and delayed initiation of appropriate antibiotics as risk factors. Cox regression analysis showed that respiratory tract source, Pitt bacteremia score, Charlson comorbidity index, and appropriate antibiotic therapy within 24 hours were independently and significantly associated with 30-day mortality outcome. Conclusions Methicillin resistance was not an independent risk factor for mortality in patients with SAB. Early, appropriate antibiotic treatment is an important prognostic factor.

Plasmin(ogen) serves as a favorable biomarker for prediction of survival in advanced high-grade serous ovarian cancer

2017 ◽  
Vol 398 (7) ◽  
pp. 765-773 ◽  
Author(s):  
Shuo Zhao ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Axel Walch ◽  
Sandra Diersch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Positive Staining ◽  
Mrna Levels ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Data Set ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Abstract In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed. In univariate Cox regression analysis, PLG staining was positively associated with prolonged overall survival (OS) [hazard ratio (HR)=0.59, p=0.026] of the patients. In multivariable analysis, PLG, together with residual tumor mass, remained a statistically significant independent prognostic marker (HR=0.49, p=0.009). In another small patient cohort (n=29), we assessed mRNA expression levels of PLG by quantitative PCR. Here, elevated PLG mRNA levels were also significantly associated with prolonged OS of patients (Kaplan-Meier analysis; p=0.001). This finding was validated by in silico analysis of a microarray data set (n=398) from The Cancer Genome Atlas (Kaplan-Meier analysis; p=0.031). In summary, these data indicate that elevated PLG expression represents a favorable prognostic biomarker in advanced (FIGO III/IV) high-grade serous ovarian cancer.

Prognostic Nomogram Incorporating Immunohistochemical Results for the Overall Survival of Patients with Bladder Cancer.

2020 ◽  
Author(s):  
Tianwei Wang ◽  
Yunyan Wang
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Bladder Cancer ◽  
Risk Model ◽  
Cox Regression ◽  
Validation Cohort ◽  
Multivariable Analysis ◽  
Clinical Information ◽  
Internal Validation ◽  
Cox Regression Analysis

Abstract Objectives: In this study, we want to combine GATA3, VEGF, EGFR and Ki67 with clinical information to develop and validate a prognostic nomogram for bladder cancer.Methods: A total of 188 patients with clinical information and immunohistochemistry were enrolled in this study, from 1996 to 2018. Univariable and multivariable cox regression analysis was applied to identify risk factors for nomogram of overall survival (OS). The calibration of the nomogram was performed and the Area Under Curve (AUC) was calculated to assess the performance of the nomogram. Internal validation was performed with the validation cohort., the calibration curve and the AUC were calculated simultaneously.Results: Univariable and multivariable analysis showed that age (HR: 2.229; 95% CI: 1.162-4.274; P=0.016), histology (HR: 0.320; 95% CI: 0.136-0.751; P=0.009), GATA3 (HR: 0.348; 95% CI: 0.171-0.709; P=0.004), VEGF (HR: 2.295; 95% CI: 1.225-4.301; P=0.010) and grade (HR: 4.938; 95% CI: 1.339-18.207; P=0.016) remained as independent risk factors for OS. The age, histology, grade, GATA3 and VEGF were included to build the nomogram. The accuracy of the risk model was further verified with the C-index. The C-index were 0.65 (95% CI, 0.58-0.72) and 0.58 (95% CI, 0.46-0.70) in the training and validation cohort respectively. Conclusions: A combination of clinical variables with immunohistochemical results based nomogram would predict the overall survival of patients with bladder cancer.

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