Genetic variations in semaphorin/neuropilin signaling to predict clinical outcome in patients (pts) with metastatic colorectal cancer (mCRC) receiving bevacizumab-based chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11608-11608
Author(s):  
Yuji Miyamoto ◽  
Fotios Loupakis ◽  
Wu Zhang ◽  
Shu Cao ◽  
Satoshi Okazaki ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Phase Iii ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Ras Mutation ◽  
Mutation Status ◽  
Gtpase Activating Proteins

11608 Background: Neuropilin ( NRP) is known to be an important VEGF co-receptor that acts as a key mediator of angiogenesis. Its ligands, semaphorins ( SEMA), compete with VEGF for NRP binding and can themselves have angiogenic activity. Plexins are also receptors of SEMAs, and have the GTPase activating proteins (GAPs) domain for RAS. NRPs are shown to signal through RAS pathways. We aimed to evaluate whether single nucleotide polymorphisms (SNPs) of genes involved in the SEMA/NRPpathways predict clinical outcome in bevacizumab-treated mCRC pts. Methods: Associations between nine SNPs in 7 genes ( SEMA3A, SEMA3D, SEMA3F, NRP1, NRP2, PLXNA1 and PLXND1) and clinical outcomes were evaluated in mCRC patients receiving first-line FOLFIRI-bevacizumab in a phase III trial: TRIBE ( N= 228). Associations between genotype and RAS mutation status with clinical outcomes was also examined. Main characteristics were the following: male/female = 138/90; median age = 60; RAS-wildtype/mutant = 55/116; median PFS = 9.7 months; median OS = 26.1 months, median follow-up time = 49.3 months. Results: NRP1 rs2228638 Any A ( N= 40) showed a significantly longer PFS compared to G/G variant ( N= 188) in the univariate (11.6 months (M) vs. 9.5 M, HR = 0.64, 95%CI = 0.43-0.95, p = 0.022) and the multivariate analysis (HR = 0.59, 95%CI = 0.38-0.90, p = 0.016). SEMA3F rs12632110 A/A ( N= 20) showed a significantly shorter PFS compared to any G variant (N = 205) in the multivariate analysis (HR = 1.89, 95%CI = 1.02-3.49, p = 0.043). Among RAS-mutant pts, SEMA3F rs12632110, SEMA3F rs1046956, SEMA3D rs7800072, NRP1 rs228638, PLXNA1 rs4679323 and PLXND1 rs2255703 polymorphisms were significantly associated with PFS in the univariate and multivariate analysis. PLXNA1 rs4679323 was also significantly associated with OS in the univariate and multivariate analysis. There was no association between these polymorphisms and outcome in patients with RASwildtype tumors. Conclusions: Genetic variants within SEMA/NRP pathways may be prognostic markers in RAS mutant mCRC patients treated with bevacizumab-based chemotherapy.

Association of a germ-line variant in the K-ras 3’ untranslated region with response and progression-free survival in patients with mCRC treated with single-agent cetuximab (IMCL-0144) or in combination with cetuximab (EPIC) independent of K-ras mutation status

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4061-4061 ◽  
Author(s):  
T. Winder ◽  
W. Zhang ◽  
A. El-Khoueiry ◽  
D. Yang ◽  
A. Pohl ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Germ Line ◽  
Direct Sequencing ◽  
Single Agent ◽  
Phase Iii ◽  
Rank Test ◽  
Wild Type ◽  
Ras Mutation ◽  
Mutation Status ◽  
Type K

4061 Background: Recent studies have found K-ras mutation status predicts response to EGFR inhibitors in mCRC. An in vitro study demonstrated let-7 microRNA family can regulate RAS expression by binding to the 3’UTR of RAS gene. Chin et al found a SNP in a let-7 microRNA complementary site (LCS) in the K-ras 3’ UTR increases cancer risk in NSCLC. We tested the hypothesis whether this SNP may be associated with clinical outcome in 130 mCRC patients enrolled in IMCL-0144 trial and in 186 pts enrolled in EPIC trial independent of K-Ras mutation status in the tumor. Methods: K-ras lcs 6 SNP was tested in 130 mCRC patients enrolled in IMC-0144 phase II clinical trial (single agent cetuximab) and in 186 mCRC patients enrolled in a second line phase III trial of cetuximab plus irinotecan versus irinotecan alone (EPIC). Genomic DNA was extracted from dissected formalin fixed paraffin embedded tumor tissue and K-ras mutation status and the polymorphism were analyzed using direct sequencing and PCR-RFLP technique. Results: The G harboring allele frequency in K-ras lcs6 was 8% in IMC-0144 and 11% in EPIC. K-ras lcs6 polymorphism was significantly associated with tumor response in patients with wild type K-ras in IMC-0144. The 12 pts harboring a G allele (TG+GG) had a 42% partial response (PR) rate compared to 55 pts with TT genotype with only 9% PR.(p=0.02, Fisher's-exact test). However, pts with TT genotype enrolled in EPIC treated with CPT-11 and cetuximab with mutant K-ras had a significantly better PFS of 12 weeks (95% CI 6.4–18) compared to those harboring the a G allele with median PFS of 6.4 weeks (95% 5.7–7) (p=0.037. log-rank test). There was no association between this polymorphism and clinical outcome in patients with wild type K-ras enrolled in EPIC. In a multivariate analysis the polymorphism remained independently associated with PFS in EPIC. Conclusions: Our data suggest for the first time that the functional germline polymorphism in K-ras lcs6 may be a potential predictive marker in mCRC patients treated with cetuximab-based chemotherapy independent of K-ras mutation status. This finding warranted further confirmative clinical trials. [Table: see text]

Effect of Manipulation under Anesthesia of the First Knee in Staged Bilateral Total Knee Arthroplasty on Clinical Outcome and Satisfaction

2020 ◽  
Author(s):  
Jung-Won Lim ◽  
Yong-Beom Park ◽  
Dong-Hoon Lee ◽  
Han-Jun Lee
Keyword(s):  
Total Knee Arthroplasty ◽  
Patient Satisfaction ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Knee Arthroplasty ◽  
Knee Flexion ◽  
Functional Score ◽  
Manipulation Under Anesthesia ◽  
Total Knee

AbstractThis study aimed to evaluate whether manipulation under anesthesia (MUA) affect clinical outcome including range of motion (ROM) and patient satisfaction after total knee arthroplasty (TKA). It is hypothesized that MUA improves clinical outcomes and patient satisfaction after primary TKA. This retrospective study analyzed 97 patients who underwent staged bilateral primary TKA. MUA of knee flexion more than 120 degrees was performed a week after index surgery just before operation of the opposite site. The first knees with MUA were classified as the MUA group and the second knees without MUA as the control group. ROM, Knee Society Knee Score, Knee Society Functional Score, Western Ontario and McMaster Universities (WOMAC) score, and patient satisfaction were assessed. Postoperative flexion was significantly greater in the MUA group during 6 months follow-up (6 weeks: 111.6 vs. 99.8 degrees, p < 0.001; 3 months: 115.9 vs. 110.2 degrees, p = 0.001; 6 months: 120.2 vs. 117.0 degrees, p = 0.019). Clinical outcomes also showed similar results with knee flexion during 2 years follow-up. Patient satisfaction was significantly high in the MUA group during 12 months (3 months: 80.2 vs. 71.5, p < 0.001; 6 months: 85.8 vs. 79.8, p < 0.001; 12 months: 86.1 vs. 83.9, p < 0.001; 24 months: 86.6 vs. 85.5, p = 0.013). MUA yielded improvement of clinical outcomes including ROM, and patient satisfaction, especially in the early period after TKA. MUA in the first knee could be taken into account to obtain early recovery and to improve patient satisfaction in staged bilateral TKA.

scholarly journals Radiomics-Derived Data by Contrast Enhanced Magnetic Resonance in RAS Mutations Detection in Colorectal Liver Metastases

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 453
Author(s):  
Vincenza Granata ◽  
Roberta Fusco ◽  
Antonio Avallone ◽  
Alfonso De Stefano ◽  
Alessandro Ottaiano ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Magnetic Resonance ◽  
Liver Metastases ◽  
Univariate Analysis ◽  
Features Selection ◽  
Ras Mutation ◽  
Mutation Status ◽  
Contrast Enhanced ◽  
Texture Parameters ◽  
Derived Data

Purpose: To assess the association of RAS mutation status and radiomics-derived data by Contrast Enhanced-Magnetic Resonance Imaging (CE-MRI) in liver metastases. Materials and Methods: 76 patients (36 women and 40 men; 59 years of mean age and 36–80 years as range) were included in this retrospective study. Texture metrics and parameters based on lesion morphology were calculated. Per-patient univariate and multivariate analysis were made. Wilcoxon-Mann-Whitney U test, receiver operating characteristic (ROC) analysis, pattern recognition approaches with features selection approaches were considered. Results: Significant results were obtained for texture features while morphological parameters had not significant results to classify RAS mutation. The results showed that using a univariate analysis was not possible to discriminate accurately the RAS mutation status. Instead, considering a multivariate analysis and classification approaches, a KNN exclusively with texture parameters as predictors reached the best results (AUC of 0.84 and an accuracy of 76.9% with 90.0% of sensitivity and 67.8% of specificity on training set and an accuracy of 87.5% with 91.7% of sensitivity and 83.3% of specificity on external validation cohort). Conclusions: Texture parameters derived by CE-MRI and combined using multivariate analysis and patter recognition approaches could allow stratifying the patients according to RAS mutation status.

Single nucleotide polymorphisms in the 20q13 amplicon genes in relation to breast cancer risk and clinical outcome

2011 ◽  
Vol 130 (3) ◽  
pp. 905-916 ◽  
Author(s):  
Hong Shi ◽  
Melanie Bevier ◽  
Robert Johansson ◽  
Ewa Grzybowska ◽  
Bowang Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Single Nucleotide Polymorphisms ◽  
Clinical Outcome ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia

2015 ◽  
Vol 53 (4) ◽  
Author(s):  
Andriy Zhydkov ◽  
Mirjam Christ-Crain ◽  
Robert Thomann ◽  
Claus Hoess ◽  
Christoph Henzen ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Blood Cells ◽  
White Blood Cells ◽  
Community Acquired Pneumonia ◽  
Adverse Clinical Outcome ◽  
C Reactive Protein ◽  
Prognostic Information ◽  
Reactive Protein

AbstractThe added value of biomarkers, such as procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC), as adjuncts to clinical risk scores for predicting the outcome of patients with community-acquired pneumonia (CAP) is in question. We investigated the prognostic accuracy of initial and follow-up levels of inflammatory biomarkers in predicting death and adverse clinical outcomes in a large and well-defined cohort of CAP patients.We measured PCT, CRP and WBC on days 1, 3, 5, and 7 and followed the patients over 30 days. We applied multivariate regression models and area under the curve (AUC) to investigate associations between these biomarkers, the clinical risk score CURB-65, and clinical outcomes [i.e., death and intensive care unit (ICU) admission].Of 925 patients with CAP, 50 patients died and 118 patients had an adverse clinical outcome. None of the initial biomarker levels significantly improved the CURB-65 score for mortality prediction. Follow-up biomarker levels showed significant independent association with mortality at days 3, 5, and 7 and with improvements in AUC. Initial PCT and CRP levels were independent prognostic predictors of adverse clinical outcome, and levels of all biomarkers during the course of disease provided additional prognostic information.This study provides robust insights into the added prognostic value of inflammatory markers in CAP. Procalcitonin, CRP, and to a lesser degree WBC provided some prognostic information on CAP outcomes, particularly when considering their kinetics at days 5 and 7 and when looking at adverse clinical outcomes instead of mortality alone.

scholarly journals Coffee Consumption, Genetic Polymorphisms, and the Risk of Type 2 Diabetes Mellitus: A Pooled Analysis of Four Prospective Cohort Studies

2020 ◽  
Vol 17 (15) ◽  
pp. 5379
Author(s):  
An Na Kim ◽  
Hyun Jeong Cho ◽  
Jiyoung Youn ◽  
Taiyue Jin ◽  
Moonil Kang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Regression Models ◽  
Coffee Consumption ◽  
Pooled Analysis ◽  
Random Effects Model ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Logistic Regression Models

The association between coffee consumption and the risk of type 2 diabetes may vary by genetic variants. Our study addresses the question of whether the incidence of type 2 diabetes is related to the consumption of coffee and whether this relationship is modified by polymorphisms related to type 2 diabetes. We performed a pooled analysis of four Korean prospective studies that included 71,527 participants; median follow-up periods ranged between 2 and 13 years. All participants had completed a validated food-frequency questionnaire (FFQ) at baseline. The odds ratios (ORs) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using logistic regression models. The ORs were combined using a fixed or random effects model depending on the heterogeneity across the studies. Compared with 0 to <0.5 cups/day of coffee consumption, the OR for type 2 diabetes was 0.89 (95% CI: 0.80–0.98, p for trend = 0.01) for ≥3 cups/day of coffee consumption. We did not observe significant interactions by five single nucleotide polymorphisms (SNPs) related to type 2 diabetes (CDKAL1 rs7756992, CDKN2A/B rs10811661, KCNJ11 rs5215, KCNQ1 rs163184, and PEPD rs3786897) in the association between coffee and the risk of type 2 diabetes. We found that coffee consumption was inversely associated with the risk of type 2 diabetes.

P5472Social economic deprivation and adverse clinical outcomes after acute coronary syndrome

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y C Lau ◽  
J Latter ◽  
A Jong ◽  
R Weir
Keyword(s):  
Clinical Outcome ◽  
Secondary Prevention ◽  
Clinical Outcomes ◽  
Statistical Difference ◽  
Independent Predictor ◽  
Composite Endpoint ◽  
Socioeconomic Deprivation ◽  
Angiotensin Ii Receptor Blocker ◽  
The Impact

Abstract Background NHS was created in 1948 to redress the healthcare inequality through provision of universal healthcare service in the UK. However even of late, significant health inequality persists. Socioeconomic deprivation is known to result in increased overall morbidity and mortality. Aim To assess the impact of socioeconomic deprivation (as categorised by Scottish Index of Multiple Deprivation, SIMD) on the medical management and clinical outcomes of patients with ACS (NSTEMI/STEMI) who were treated with PCI Methods A retrospective study of NSTEMI/NSTEMI patients after inpatient treatment with coronary angiogram and PCI. The parameters include basic demographics, risk factors, LV EF on echocardiogram, lipid profile and discharge medication. Individual's socioeconomic deprivation index, as described SIMD was also recorded (1 – most deprived and 10 – least deprived), and accordingly placed into quintile (SIMD 1–2, 3–4, 5–6,7 –8, 9–10). Follow-up for 24 months. Clinical outcome assessed was composite endpoint event of MACE. Results 357 from the lowest quintile (SIMD 1–2), 319 from SIMD 3–4, 191 from SIMD 5–6, 120 from SIMD 7–8, and 99 from the highest quintile (SIMD 9–10) were included. No statistical difference exists between age or gender. No difference in past medical history (inclusive of hypertension, diabetes, dyslipidemia, family history. No difference in incidence of nicotine use. Prescription of aspirin, P2Y12 inhibitors (clopidogrel, ticagrelor or prasugrel) as well as secondary prevention medications (such as ace inhibitor/angiotensin II receptor blocker, beta blocker, statin and GTN) were good and not statistically different between all groups. No statistical difference exists between all groups relating to pre-discharge LV ejection fraction on echocardiogram or random cholesterol level check on admission. 24 months follow-up demonstrated composite endpoint of MACE was statistically higher among patients of lowest socioeconomic quintile (Kaplan Meier plot, p<0.001). Step-wise multiple regression analysis also confirmed multiple socioeconomic deprivation as an independent predictor for more adverse clinical outcomes (p<0.001, R2=14.5%). Patients from the least deprived quintile possess survival advantage almost 14-folds as compared to those of most deprived group (Odd-ratio 13.8 (95% CI: 39.4–48.5)). Summary After an ACS event, despite initial coronary intervention and subsequent optimal prescription of prognostically beneficial secondary prevention medications, patients from the lower socioeconomic group (as described by SIMD) are still more likely to experience readmission for cardiovascular death, non-fatal myocardial infarction and non-fatal stroke. Socioeconomic deprivation has been shown to be an independent predictor of adverse clinical outcome for those who survived initial ACS. Acknowledgement/Funding None

Clinical Outcomes, Tendon Integrity, and Shoulder Strength After Revision Rotator Cuff Reconstruction: A Minimum 2 Years’ Follow-up

2018 ◽  
Vol 46 (11) ◽  
pp. 2700-2706 ◽  
Author(s):  
Lukas Willinger ◽  
Lucca Lacheta ◽  
Knut Beitzel ◽  
Stefan Buchmann ◽  
Klaus Woertler ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Constant Score ◽  
Case Series ◽  
Shoulder Function ◽  
Dash Score ◽  
Outcome Scores ◽  
Retear Rate

Background: The retear rate after primary rotator cuff (RC) reconstruction is high and commonly leads to poorer clinical outcomes and shoulder function. In the case of primary failure, revision RC reconstruction (RCR) has become increasingly important to re-create RC integrity and improve outcomes. To date, clinical and structural outcomes after RCR have not been sufficiently investigated and described at midterm follow-up. Hypothesis/Purpose: The purpose was to evaluate the clinical and radiological outcomes after revision RCR. It was hypothesized that revision RCR significantly improves clinical outcomes and that the outcomes positively correlate with tendon integrity on magnetic resonance imaging (MRI). Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent revision RCR between 2008 and 2014 were retrospectively evaluated with a minimum follow-up of 2 years. Outcomes were assessed by a clinical examination, a visual analog scale for pain (VAS), the Constant Score (CS), the American Shoulder and Elbow Surgeons (ASES) score, and the Disabilities of the Arm, Shoulder and Hand (DASH) score. Tendon integrity was determined using 3-T MRI and graded according to the Sugaya classification. Results: Thirty-one of 40 patients (77.5%) were available for the final assessment at a mean follow-up of 50.3 ± 20.4 months. Clinical outcome scores significantly improved from preoperatively to postoperatively for the CS (39.7 ± 16.7 to 65.1 ± 19.7; P < .001), ASES (44.2 ± 17.7 to 75.2 ± 24.8; P < .001), and DASH (68.6 ± 15.1 to 21.5 ± 19.1; P < .001). The VAS score decreased from 6.1 ± 1.8 preoperatively to 1.3 ± 1.8 at final follow-up ( P < .001). MRI demonstrated a retear rate of 55.5%. No differences in CS, ASES, and DASH scores were detected between patients with an intact repair and failure. Abduction strength was not significantly different in patients with an intact repair and retears (55.5 N vs 44.0 N, respectively, P = .52). Conclusion: Revision RCR improves clinical outcomes and shoulder function at midterm follow-up. The clinical outcome scores were comparable in patients with an intact repair and those with failed RC healing. Therefore, tendon integrity was not correlated with better clinical outcomes after revision RCR at final follow-up.

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