γ-H2AX as a novel prognostic marker in patients with non-small lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17553-e17553
Author(s):  
Dimitrios Matthaios ◽  
Panagiotis Hountis ◽  
Grigorios Trypsianis ◽  
Athanasios Zissimopoulos ◽  
Demosthenes Bouros ◽  
...  

e17553 Background: Phosphorylation of the H2AX histone is an early indicator of DNA double-strand breaks and of the resulting DNA damage response. In the present study we assessed the expression of γ-Η2ΑΧ in a cohort of 96 patients with non-small cell lung carcinoma and evaluated its role as a prognostic indicator in resectable NCSLC patients. Methods: 96 parafin-embedded specimens of non-small lung cancer patients were examined. All patients underwent radical thoracic surgery of primary tumor (lobectomy or pneumonectomy) and regional lymph nodes dissection. γ-Η2ΑΧ expression was assessed by standard immunohistochemistry.Multivariate Cox proportional hazards regression analysis, using a backward selection approach, were performed to explore the independent effect of variables on survival. All tests were two tailed and statistical significance was considered for p values <0.05. Results: Follow-up was available for all patients; mean duration of follow-up was 27.50 ± 14.07 months (range 0.2-57 months, median 24 months). Sixty-three patients (65.2%) died during the follow-up period. The mean survival time was 32.2 ± 1.9 months (95% CI = 28.5 to 35.8 months; median 30.0 months); one, two and three-year survival rates were 86.5 ± 3.5%, 57.3 ± 5.1% and 37.1 ± 5.4% respectively. Low γ-H2AX expression was associated with a significant better survival as compared with those having high γ-H2AX expression (23.2 months for high γ-Η2ΑΧ expressin vs 35.3 months for low γ-H2AX expression, p=0.009; HR=1.95, 95% CI=1.15-3.30). Further investigation with multivariate Cox proportional hazards regression analysis revealed that high expression of γ-H2AX remained independent prognostic factors of worse overall survival (HR=2.15, 95% CI=1.22-3.79, p=0.026). Conclusions: Our study is the first study to demonstrate that overexpression of γ-Η2ΑΧ is an independent prognostic indicator of worse overall survival in patients with non-small lung cancer. Further studies are needed to confirm our results.

2020 ◽  
Vol 163 (5) ◽  
pp. 986-991
Author(s):  
Jordan I. Teitelbaum ◽  
Khalil Issa ◽  
Ian R. Barak ◽  
Feras Y. Ackall ◽  
Sin-Ho Jung ◽  
...  

Objective To determine whether treatment of sinonasal squamous cell carcinoma (SCC) at a high-volume facility affects survival. Study Design Retrospective database analysis. Setting National Cancer Database (2004-2014). Subjects and Methods The National Cancer Database was queried for sinonasal SCC from 2004 to 2014. Patient demographics, tumor characteristics and classification, resection margins, treatment regimen, and facility case-specific volume—averaged per year and grouped in tertiles as low (0%-33%), medium (34%-66%), and high (67%-100%)—were compared. Overall survival was compared with Cox proportional hazards regression analysis. Results A total of 3835 patients treated for sinonasal SCC between 2004 and 2014 were identified. Therapeutic options included surgery alone (18.6%), radiotherapy (RT) alone (29.1%), definitive chemoradiation (15.4%), surgery with adjuvant RT (22.8%), and combinations (14.1%) of the aforementioned treatments. Patients who underwent surgery with adjuvant RT had better overall survival (hazard ratio [HR], 0.74; P < .001; 95% CI, 0.63-0.86). As for treatment volume per facility, 7.4% of patients were treated at a low-volume center, 17.5% at a medium-volume center, and 75.1% at a high-volume center. Univariate analysis showed that treatment at a high-volume facility conferred a significantly better overall survival (HR, 0.77; P = .002). Multivariable Cox proportional hazards regression analysis, adjusting for age, sex, tumor classification, and treatment regimen, demonstrated that patients who underwent treatment at a high-volume facility (HR, 0.81; P < .001) had significantly improved survival. Conclusion This study shows a better overall survival for sinonasal SCC treated at high-volume centers. Further study may be needed to understand the effect of case volume on the paradigms of sinonasal SCC management.


2021 ◽  
pp. 1-21
Author(s):  
Anne Mette L. Würtz ◽  
Mette D. Hansen ◽  
Anne Tjønneland ◽  
Eric B. Rimm ◽  
Erik B. Schmidt ◽  
...  

ABSTRACT Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29,142 women and 26,029 men aged 50-64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazards ratios (HR) with 95% CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13.6 years of follow-up, 656 female and 1,694 male cases were identified. Among women, the adjusted HR for MI was 1.02 (95% CI: 0.93, 1.13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0.93 (95% CI: 0.77, 1.13) for replacement of potatoes with fruiting vegetables and 0.91 (95% CI: 0.77, 1.07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.


2021 ◽  
Author(s):  
Sanhe Liu ◽  
Yongzhi Li ◽  
Diansheng Cui ◽  
Yuexia Jiao ◽  
Liqun Duan ◽  
...  

Abstract BackgroundDifferent recurrence probability of non-muscle invasive bladder cancer (NMIBC) requests different adjuvant treatments and follow-up strategies. However, there is no simple, intuitive, and generally accepted clinical recurrence predictive model available for NMIBC. This study aims to construct a predictive model for the recurrence of NMIBC based on demographics and clinicopathologic characteristics from two independent centers. MethodsDemographics and clinicopathologic characteristics of 511 patients with NMIBC were retrospectively collected. Recurrence free survival (RFS) was estimated using the Kaplan-Meier method and log-rank tests. Univariate Cox proportional hazards regression analysis was used to screen variables associated with RFS, and a multivariate Cox proportional hazards regression model with a stepwise procedure was used to identify those factors of significance. A final nomogram model was built using the multivariable Cox method. The performance of the nomogram model was evaluated with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed with bootstrap resampling. X-tile software was used for risk stratification calculated by the nomogram model. ResultsIndependent prognostic factors including tumor stage, recurrence status, and European Association of Urology (EAU) risk stratification group were introduced to the nomogram model. The model showed acceptable calibration and discrimination (area under the receiver operating characteristic [ROC] curve was 0.85; the consistency index [C-index] was 0.79 [95% CI: 0.76 to 0.82]), which was superior to the EAU risk stratification group alone. The decision curve also proved well clinical usefulness. Moreover, all populations could be stratified into three distinct risk groups by the nomogram model. ConclusionsWe established and validated a novel nomogram model that can provide individual prediction of RFS for patients with NMIBC. This intuitively prognostic nomogram model may help clinicians in postoperative treatment and follow-up decision-making.


Cardiology ◽  
2018 ◽  
Vol 139 (4) ◽  
pp. 212-218 ◽  
Author(s):  
Yun Shen ◽  
Xueli Zhang ◽  
Yiting Xu ◽  
Qin Xiong ◽  
Zhigang Lu ◽  
...  

Objectives: To investigate whether serum fibroblast growth factor 21 (FGF21) levels can be used to predict the future development of major adverse cardiovascular events (MACEs). Methods: This study included 253 patients who received subsequent follow-up, and complete data were collected for 234 patients. Independent predictors of MACEs were identified by using the Cox proportional-hazards regression analysis. The prognostic value of FGF21 levels for MACEs was evaluated by Kaplan-Meier survival analysis. Results: Of 229 patients finally enrolled in the analysis, 27/60 without coronary artery disease (CAD) at baseline experienced a MACE, and 132/169 patients with CAD at baseline experienced a MACE. Among patients with CAD at baseline, serum FGF21 levels were significantly higher in patients with MACEs (p < 0.05) than in patients without MACEs. Kaplan-Meier survival analysis showed patients with a higher serum FGF21 had a significantly lower event-free survival (p = 0.001) than those with a lower level. Further Cox proportional-hazards regression analysis, including the traditional risk factors for cardiovascular disease, showed that serum FGF21 was an independent predictor of MACE occurrence. Conclusions: In patients with CAD at baseline, an elevated serum FGF21 level was associated with the development of a MACE in the future.


2014 ◽  
Vol 58 (12) ◽  
pp. 7468-7474 ◽  
Author(s):  
W. Picard ◽  
F. Bazin ◽  
B. Clouzeau ◽  
H.-N. Bui ◽  
M. Soulat ◽  
...  

ABSTRACTTo assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ± 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1-1
Author(s):  
Roberto Machado ◽  
Martin Steinberg ◽  
Duane Bonds ◽  
Samir Ballas ◽  
William Blackwelder ◽  
...  

Abstract Pulmonary hypertension [PH-tricuspid regurgitant jet velocity (TRV) ≥2.5 m/s] is a common complication of sickle cell disease associated with high mortality. Identification of biomarkers of PH and mortality could facilitate screening and risk stratification in this population. Validated biomarkers would provide methods for retrospective evaluation of the prevalence and prognosis of PH in large historical cohorts of patients such as the Multicenter Study of Hydroxyurea in Sickle Cell Anemia(MSH). Because brain natriuretic peptide(BNP) is released from the ventricles during pressure strain, we hypothesized that BNP levels would correlate with the severity of PH and prospective risk of death in patients with SCD. BNP was measured in 45 African-American control subjects and 230 patients with SCD. Median (interquartile range) BNP(pg/ml) was higher in patients with PH than patients without PH or controls[+PH: 206(81–701),-PH: 47(26–104), C: 29, P&lt;0.001]. BNP levels directly correlated with age (R=0.32, P&lt;0.001), creatinine (R=0.22, P&lt;0.001), LDH(R=0.31, P&lt;0.001), TRV (R=0.5, P&lt;0.001), pulmonary vascular resistance (R=0.5, P=0.001); and inversely with hemoglobin(R=0.41, P&lt;0.001), cardiac output(R=0.47, P= 0.003) and 6-minute walk distance(R=0.51, P=0.001). The area under the ROC for BNP and the diagnosis of pulmonary hypertension was 0.84 (P&lt;0.001). A cutoff value of 160 pg/ml (corresponding to the 75th percentile for the population) had 58% sensitivity and 98% specificity for the diagnosis of PH. Cox proportional hazards regression identified BNP as an independent predictor of mortality(RR 2.17,95% CI 1.2–3.8, P =0.001) with clear mortality break point at the 75th percentile(160 pg/ml). To independently explore the prevalence and associated risk of PH in patients with sickle cell disease, a BNP value of 160 pg/ml was used as an indicator of PH. BNP levels were then measured in plasma samples collected in 121 patients who were enrolled in the MSH patient’s follow-up study that started in 1996. These patients had received hydroxyurea or placebo for two years, had moderately severe disease based on study entry criteria, and had 9-years of comprehensive follow-up. An abnormal BNP level ≥160 pg/ml was present in 30% of patients in the MSH cohort. BNP levels correlated directly with age(R=0.35, P&lt;0.001) and creatinine (R=0.24, P&lt;0.001), and inversely with hemoglobin(R=−0.54, P&lt;0.001). There was no correlation between BNP and rate of painful episodes or acute chest syndrome, use of hydroxyurea or leukocyte count. A high BNP level in the MSH cohort was associated with mortality by logistic regression(OR 3.04,95% CI 1.2–7.6, P = 0.018) and Cox proportional hazards regression analysis(RR 2.87, P=0.017). The relationship remained significant for continuous log- transformed BNP values and after adjustment for other covariates. These studies confirm that PH is common, mechanistically linked to hemolytic anemia and the major risk factor for death in SCD. Provocatively, the MSH analysis suggests that rates of pain episodes in this small sample of seriously ill patients were unrelated to risk of death: this risk was largely determined by a high BNP level, which is probably explained by undiagnosed hemolysis-associated PH.


2021 ◽  
Author(s):  
Qiuju Wang ◽  
Yanzhen Zhao ◽  
Yan Chen ◽  
Yibo Chen ◽  
Xiaoyu Song ◽  
...  

Abstract PurposeT-cadherin is an immunoglobulin-like adhesion molecule which acts as a tumor suppressor gene, programmed cell death ligand 1 (PD-L1) is a cell surface protein that involves in the suppression of the immune system. This study aimed at exploring the correlation between T-cadherin and PD-L1, as well as their prognostic value in patients with HPV-negative head and neck squamous cell carcinoma (HNSCC). MethodsIn this study, immunohistochemical staining was used to determine the protein expression of T-cadherin and PD-L1 in 104 tissue specimens of HPV-negative HNSCC. Spearman linear correlation analysis was used to determine the association between protein expression of T-cadherin and PD-L1. Kaplan-Meier analysis was used to plot overall survival (OS) and disease-free survival (DFS) curves. Cox proportional hazards regression analysis was used to conduct univariate and multivariate analysis. ResultsThe results showed a large negative association between protein expression of T-cadherin and PD-L1 (r=-0.775, P<0.01), expression of T-cadherin and PD-L1 were associated with OS (P=0.021 and 0.034, respectively) and DFS (P=0.012 and 0.016, respectively) in patients with HPV-negative HNSCC. Cox proportional hazards regression analysis revealed that expression of T-cadherin and PD-L1 were independent prognostic predictors for OS and DFS in patients with HPV-negative HNSCC. The worst prognosis was observed in patients with T-cadherin negative/PD-L1 positive.ConclusionIn conclusion, expression of T-cadherin and PD-L1 were inversely correlated and were independent prognostic factors for patients with HPV-negative HNSCC.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Masaki Hara ◽  
Naozumi Saiki ◽  
Hiroki Suzuki ◽  
Masamitsu Ubukata ◽  
Rin Asao ◽  
...  

Abstract Background and Aims There are several reports that the initial (within one year) failure of vascular access (VA) is 2–53% in several countries. Malnutrition alone, inflammation alone, and anemia alone are factors that have a well-known relationship to VA failure. We believe that the relationship of these risk factors to VA failure is a complex one. Therefore, we evaluated whether the addition of these factors had a synergistic impact on VA failure. Method This longitudinal cohort study sought to confirm the effects of malnutrition, inflammation, and anemia on VA failure. We included 177 patients with chronic kidney disease (CKD) with first-time arteriovenous fistulas who were treated from January 2013 to December 2017. VA failure was defined as a new onset of VA obstruction or the need for percutaneous transluminal angioplasty. Albumin (Alb), C-reactive protein (CRP), and hemoglobin (Hb) were studied as indicators for malnutrition, inflammation, and anemia, respectively. Each highest (CRP) or lowest (Alb and Hb) interquartile range (IQR) group was assigned 1 point (as a risk score). The cumulative VA failure rate was analyzed by the Kaplan-Meier method, which stratified the study cohort into four groups according to the risk scores (0–3). We assessed whether the lowest IQR group of Hb and Alb, and the highest IQR group of CRP were associated with VA failure. To determine this, we used a univariable Cox proportional hazards regression analysis to calculate the hazard ratio (HR) and its 95% confidence interval (CI). A multivariable Cox proportional hazards regression analysis was used to evaluate the association between the risk score and VA failure, with adjustment for age, sex, presence or absence of diabetes mellitus, value of calcium phosphate products, preoperative vein diameter, and intraoperative vascular assessment scores. Results The average observational period was 1.6±1.4 years. The incidence of VA failure was 30.5% (54 patients). Cumulative VA failure was significantly higher in patients who had more than two risk scores, as compared to the patients who did not have any risk score (Figure). The univariate Cox regression analysis showed that Alb, CRP, and Hb were significantly associated with VA failure (HR, 2.00; 95% CI, 1.08–3.71 for Alb and HR, 2.21; 95% CI, 1.15–4.13 for CRP and HR, 1.96; 95% CI, 1.02–3.63 for Hb), respectively. The presence of more than two risk scores was significantly associated with VA failure (HR, 4.68; 95% CI, 1.07–18.5 for the patients with two risk scores and HR, 4.72; 95% CI, 1.32–17.2 for the patients with three risk scores). Conclusion Malnutrition, inflammation, and anemia independently and synergistically affect VA failure. In clinical settings, we need to be aware of the presence of malnutrition, inflammation, and anemia to better prevent VA failure.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 615-615
Author(s):  
Liam Connor Macleod ◽  
Scott S. Tykodi ◽  
Sarah Holt ◽  
John L. Gore

615 Background: Many patients with metastatic kidney cancer (mRCC) are ineligible for trials due to non-clear cell histology. Efficacy of targeted therapy agents in non-clear cell mRCC is still being investigated. We hypothesized that sequencing CN upfront is associated with improved overall survival. We analyze a population-based cohort of non-clear cell mRCC patients in the targeted therapy era. Methods: Patients from the SEER-Medicare files (2005-2011) with non-clear cell mRCC were categorized as having received upfront targeted therapy or upfront CN. Additional exclusions were age < 66 to avoid confounding by uncaptured non-Medicare coverage, and competing stage IV cancer. Targeted therapy was identified through Medicare Part D files. Cox proportional hazards regression determined association between treatment groups, clinical and cancer-related characteristics, and the main outcome, median overall survival (OS). Propensity matching controlled for measurable confounding in treatment selection. Results: Of 1,326 mRCC cases, 528 met inclusion criteria of whom 433 (82%) received targeted agents and 172 (33%) underwent CN. Of those not having CN, 74% were diagnosed by biopsy, 10% by cytology, and 16% radiographically (confirmed at autopsy). Thirteen percent received CN then targeted therapy (OS 14 mos, IQR 9-25), 2.5% received targeted therapy then CN (OS 14 mos, IQR 9-26), 18% received CN only (OS 14 mos, IQR5-40), 67% received targeted therapy only (OS 9 mos, IQR 4-19). On multivariable Cox proportional hazards regression upfront CN (regardless of post-CN therapy) was associated with improved OS (HR 0.54,95% CI 0.41,0.72). Using propensity scores, upfront CN patients (N = 161) were matched to upfront targeted therapy patient (N = 111) and the average treatment effect of CN was 8.3 months survival improvement (95% CI 4.0, 13.2). Conclusions: Although utilization of targeted agents in non-clear cell mRCC exceeds 80%, those with greatest OS received CN either upfront or after targeted therapy, though the latter was rare (2.5%). The variety of sequencing strategies observed is evidence of uncertainty regarding the best care for non-clear cell mRCC patients given limited options.


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