Polymorphism in Gene for ABCC2 Transporter Predicts Methotrexate Drug Survival in Patients with Psoriasis

Background and Objectives: Methotrexate is widely prescribed for the treatment of moderate-to-severe psoriasis. As drug survival encompasses efficacy, safety, and treatment satisfaction, such studies provide insights into successful drug treatments in the real-life scenario. The objective was to define methotrexate drug survival and reasons for discontinuation, along with factors associated with drug survival, in a cohort of adult patients with moderate-to-severe plaque psoriasis. Materials and Methods: Data on methotrexate treatment were extracted from our institutional registry. Drug survival was estimated by Kaplan–Meier analysis, and predictors of drug survival were analyzed by Cox proportional hazards regression. Results: We included 133 patients treated with methotrexate. Due to significant effects of the year of treatment initiation, drug survival analysis was performed for 117 patients who started methotrexate in 2010 or later. Median methotrexate drug survival was 11.0 months. Overall, 89% of patients discontinued treatment, with over half of these (51%) due to lack of efficacy. Significantly longer drug survival was seen for patients who discontinued treatment due to lack of efficacy versus drug safety (p = 0.049); when stratified by sex, this remained significant only for women (p = 0.002). The patient ABCC2 rs717620 genotype was significantly associated with drug survival in both univariate log-rank and multivariate Cox regression analyses, with variant T allele associated with longer drug survival (hazard ratio, 0.606; 95% confidence interval, 0.380–0.967; p = 0.036). Conclusions: We have identified the novel association of patient ABCC2 rs717620 genotype with methotrexate drug survival. This pharmacogenetic marker might thus help in the management of psoriasis patients in daily practice.

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Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa085 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Kyle W Singleton ◽

Alyx B Porter ◽

Leland S Hu ◽

Sandra K Johnston ◽

Kamila M Bond ◽

...

Keyword(s):

Treatment Response ◽

Proportional Hazards ◽

Cox Regression ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Recurrent Glioblastoma ◽

Response To Therapy ◽

Cytotoxic Therapy ◽

Kaplan Meier ◽

Recurrent Gbm

Abstract Background Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze days gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies. Methods DG response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N = 62). Kaplan–Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM. Results In patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan–Meier analysis showed significant differences in OS and PFS at DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy patients. Conclusion DG has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.

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Effect of Health Care Provider Delays on Short-Term Outcomes in Patients With Colorectal Cancer: Multicenter Population-Based Observational Study

Interactive Journal of Medical Research ◽

10.2196/15911 ◽

2020 ◽

Vol 9 (3) ◽

pp. e15911

Author(s):

Ahmed Abdulaal ◽

Chanpreet Arhi ◽

Paul Ziprin

Keyword(s):

Colorectal Cancer ◽

Observational Study ◽

Proportional Hazards ◽

Cox Regression ◽

Diagnostic Delay ◽

Population Based ◽

Cox Proportional Hazards ◽

Treatment Delays ◽

Cox Regression Analysis ◽

Kaplan Meier

Background The United Kingdom has lower survival figures for all types of cancers compared to many European countries despite similar national expenditures on health. This discrepancy may be linked to long diagnostic and treatment delays. Objective The aim of this study was to determine whether delays experienced by patients with colorectal cancer (CRC) affect their survival. Methods This observational study utilized the Somerset Cancer Register to identify patients with CRC who were diagnosed on the basis of positive histology findings. The effects of diagnostic and treatment delays and their subdivisions on outcomes were investigated using Cox proportional hazards regression. Kaplan-Meier plots were used to illustrate group differences. Results A total of 648 patients (375 males, 57.9% males) were included in this study. We found that neither diagnostic delay nor treatment delay had an effect on the overall survival in patients with CRC (χ23=1.5, P=.68; χ23=0.6, P=.90, respectively). Similarly, treatment delays did not affect the outcomes in patients with CRC (χ23=5.5, P=.14). The initial Cox regression analysis showed that patients with CRC who had short diagnostic delays were less likely to die than those experiencing long delays (hazard ratio 0.165, 95% CI 0.044-0.616; P=.007). However, this result was nonsignificant following sensitivity analysis. Conclusions Diagnostic and treatment delays had no effect on the survival of this cohort of patients with CRC. The utility of the 2-week wait referral system is therefore questioned. Timely screening with subsequent early referral and access to diagnostics may have a more beneficial effect.

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Predicting Metastatic Potential in Pheochromocytoma and Paraganglioma: A Comparison of PASS and GAPP Scoring Systems

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa608 ◽

2020 ◽

Vol 105 (12) ◽

pp. e4661-e4670

Author(s):

Heather Wachtel ◽

Troy Hutchens ◽

Ezra Baraban ◽

Lauren E Schwartz ◽

Kathleen Montone ◽

...

Keyword(s):

Proportional Hazards ◽

Cox Regression ◽

Intraclass Correlation ◽

Scoring Systems ◽

Metastatic Potential ◽

Disease Recurrence ◽

Cox Proportional Hazards ◽

Ki 67 ◽

Kaplan Meier ◽

Adrenal Pheochromocytoma

Abstract Purpose The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict metastatic potential in pheochromocytomas (PCC) and paragangliomas (PGLs). The goal of this study is to assess PASS and GAPP as metastatic predictors and to correlate with survival outcomes. Methods The cohort included PCC/PGL with ≥5 years of follow-up or known metastases. Surgical pathology slides were rereviewed. PASS and GAPP scores were assigned. Univariable and multivariable logistic regression, Kaplan–Meier survival analysis, and Cox proportional hazards were performed to assess recurrence-free survival (RFS) and disease-specific survival (DSS). Results From 143 subjects, 106 tumors were PCC and 37 were PGL. Metastases developed in 24%. The median PASS score was 6.5 (interquartile range [IQR]: 4.0-8.0) and median GAPP score was 3.0 (IQR: 2.0-4.0). Interrater reliability was low–moderate for PASS (intraclass correlation coefficient [ICC]: 0.6082) and good for GAPP (ICC 0.7921). Older age (OR: 0.969, P = .0170) was associated with longer RFS. SDHB germline pathogenic variant (OR: 8.205, P = .0049), extra-adrenal tumor (OR: 6.357, P < .0001), Ki-67 index 1% to 3% (OR: 4.810, P = .0477), and higher GAPP score (OR: 1.537, P = .0047) were associated with shorter RFS. PASS score was not associated with RFS (P = .1779). On Cox regression, a GAPP score in the moderately differentiated range was significantly associated with disease recurrence (HR: 3.367, P = .0184) compared with well-differentiated score. Conclusion Higher GAPP scores were associated with aggressive PCC/PGL. PASS score was not associated with metastases and demonstrated significant interobserver variability. Scoring systems for predicting metastatic PCC/PGL may be improved by incorporation of histopathology, clinical data, and germline and somatic tumor markers.

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THE PROGNOSTIC SIGNIFICANCE OF CD3+, CD68+, CD20+ INTERSTITIAL CELLS IN PATIENTS WITH KIDNEY ALLOGRAFT GLOMERULITIS

Nephrology (Saint-Petersburg) ◽

10.24884/1561-6274-2018-22-6-47-55 ◽

2018 ◽

Vol 22 (6) ◽

pp. 47-55

Author(s):

V. A. Dobronravov ◽

A. O. Mukhametdinova ◽

M. S. Khrabrova ◽

A. Nabokow ◽

H. -J. Gröne ◽

...

Keyword(s):

Proportional Hazards ◽

Cox Regression ◽

Prognostic Significance ◽

Cox Proportional Hazards ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Long Term Prognosis ◽

The Impact ◽

The Relationship

THE OBJECTIVEof the study was to assess the impact of the count of interstitial CD3+, CD68+ and CD20+ cells on long-term prognosis of renal allograft (RA).PATIENTS AND METHODS.86 RA recipients with biopsy-proven according to the Banff 2013- 2017 criteria glomerulitis were enrolled in this retrospective study. The patients were subdivided into the following groups: 1) isolated glomerulitis with negative donor-specific antibodies (DSA) at the biopsy (n=53); 2) glomerulitis with positive DSA (n=22); 3) glomerulitis with undetermined DSA (n=11). Quantitative assay of interstitial positive cells was performed after immunohistochemical staining for CD68+, CD3+, CD20+. The Kaplan-Meier method and Cox proportional hazards regression model were used for the analysis of the relationship between interstitial CD3+, CD68+, CD20+ cells and risk of RA loss.RESULTS.CD68+ and CD3+ cells prevailed in interstitium in RA glomerulitis. CD20+ infiltrates were found in 60% of cases. CD20+ cells tended to form infiltrates, in 9 cases these infiltrates reached large sizes (≥ 50 CD20+ lymphocytes) and formed nodular structures. There was no difference in the count of interstitial CD3+ and CD68+ cells and in the presence of CD20+ infiltrates between DSA subgroups. Interstitial CD68+ ≥ 5 cells per field of view (FOV) (x400) and CD3+ ≥ 8 cells per FOV (x400), as well as the presence of large CD20+ infiltrates were associated with a lower RA survival (plog-rank < 0,05). Interstitial CD68+ (≥ 5 cells/FOV), CD3 + (≥ 8 cells/FOV) and the presence of large CD20+ interstitial infiltrates were independently associated with the risk of RA loss in the multivariable Cox regression analysis adjusted for DSA, cold and warm ischemia time (p < 0.05). CONCLUSION. Grade of interstitial infiltration by CD68+, CD3+ and CD20+ cells in RA glomerulitis could be independent predictor of RA loss.

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Effect of Health Care Provider Delays on Short-Term Outcomes in Patients With Colorectal Cancer: Multicenter Population-Based Observational Study (Preprint)

10.2196/preprints.15911 ◽

2019 ◽

Author(s):

Ahmed Abdulaal ◽

Chanpreet Arhi ◽

Paul Ziprin

Keyword(s):

Colorectal Cancer ◽

Observational Study ◽

Proportional Hazards ◽

Cox Regression ◽

Diagnostic Delay ◽

Population Based ◽

Cox Proportional Hazards ◽

Treatment Delays ◽

Cox Regression Analysis ◽

Kaplan Meier

BACKGROUND The United Kingdom has lower survival figures for all types of cancers compared to many European countries despite similar national expenditures on health. This discrepancy may be linked to long diagnostic and treatment delays. OBJECTIVE The aim of this study was to determine whether delays experienced by patients with colorectal cancer (CRC) affect their survival. METHODS This observational study utilized the Somerset Cancer Register to identify patients with CRC who were diagnosed on the basis of positive histology findings. The effects of diagnostic and treatment delays and their subdivisions on outcomes were investigated using Cox proportional hazards regression. Kaplan-Meier plots were used to illustrate group differences. RESULTS A total of 648 patients (375 males, 57.9% males) were included in this study. We found that neither diagnostic delay nor treatment delay had an effect on the overall survival in patients with CRC (χ23=1.5, P=.68; χ23=0.6, P=.90, respectively). Similarly, treatment delays did not affect the outcomes in patients with CRC (χ23=5.5, P=.14). The initial Cox regression analysis showed that patients with CRC who had short diagnostic delays were less likely to die than those experiencing long delays (hazard ratio 0.165, 95% CI 0.044-0.616; P=.007). However, this result was nonsignificant following sensitivity analysis. CONCLUSIONS Diagnostic and treatment delays had no effect on the survival of this cohort of patients with CRC. The utility of the 2-week wait referral system is therefore questioned. Timely screening with subsequent early referral and access to diagnostics may have a more beneficial effect.

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Abstract 131: Cognitive Impairment Predicts Mortality in Patients with Heart Failure

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.9.suppl_2.131 ◽

2016 ◽

Vol 9 (suppl_2) ◽

Author(s):

Howard Lan ◽

Lee Ann Hawkins ◽

Helme Silvet

Keyword(s):

Heart Failure ◽

Cognitive Impairment ◽

Proportional Hazards ◽

Cox Regression ◽

Cox Proportional Hazards ◽

Mortality Data ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Study Population

Introduction: In our previously published study, we evaluated a Veteran cohort of 250 outpatients with heart failure (HF) and found 58% (144 of 250) incidence of previously undiagnosed cognitive impairment (CI). Previous studies have suggested that HF patients with CI have worse clinical outcomes including higher mortality but this has not been studied in the Veteran population. Methods: Current study was designed to prospectively follow this cohort of 250 patients. Cognitive function was previously evaluated in all patients at baseline using the St. Luis University Mental Status (SLUMS) exam. The primary outcome for this follow-up study was all-cause mortality. Data analysis including Cox regression analysis and Kaplan-Meier curves were generated using SPSS. Results: The study population was predominantly Caucasian (72%, 179 of 250) and male (99%, 247 of 250) with mean age of 69 ± 10 years. Mean follow up was 31 ± 11 months. During follow up, 26% (64 of 250) of patients died. Univariate and multivariate Cox proportional hazards regression analyses were performed and shown in Table 1. Using the SLUMS score, subjects were stratified into three groups: no CI (42%, 106 of 250), mild CI (42%, 104 of 250), and severe CI (16%, 40 of 250). Kaplan-Meier survival curves were generated to compare the three CI groups in Figure 1. Conclusion: Current study demonstrates that CI is an independent risk factor for mortality in outpatient HF patients. This is an important finding because CI is commonly unrecognized in this vulnerable population. Routine CI screening could help to identify those who are at greater risk for worse outcomes. Future studies are needed to derive possible interventions to improve outcomes in these patients.

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Surgical Outcomes of Vaginal or Cervical Melanoma

Frontiers in Surgery ◽

10.3389/fsurg.2021.771160 ◽

2022 ◽

Vol 8 ◽

Author(s):

Hui Tian ◽

Xuan Wang ◽

Bin Lian ◽

Lu Si ◽

Min Gao ◽

...

Keyword(s):

Adjuvant Therapy ◽

Proportional Hazards ◽

Cox Regression ◽

Radical Resection ◽

Cox Proportional Hazards ◽

Cox Regression Analysis ◽

Resection Group ◽

Kaplan Meier ◽

Significant Difference ◽

Peking University

Objective: To evaluate the effectiveness of radical resection compared with non-radical resection for vaginal or cervical melanoma.Methods: We retrospectively analysed the clinical data of post-operative patients with primary lower genital tract melanoma hospitalised at Peking University Cancer Hospital between Jan 2014 and Dec 2020. The study endpoints were recurrence-free survival (RFS) and overall survival (OS). Kaplan–Meier method-plotted survival curves and univariate and multivariate Cox proportional hazards regression models were used to identify the factors associated with RFS and OS, and to calculate hazard ratios (HRs) and associated 95% confidence intervals (95% CIs).Results: A total of 80 patients were included. Thirty-one patients had received non-radical resection, and 49 patients had received radical resection. The median patient age was 55.5 (IQR 45.3–60.0) years. Sixty-two (77.5%) patients had vaginal melanoma. Sixty-four patients (80.0%) had received post-operative adjuvant therapy. The median follow-up time was 36.0 months (95% CI 10.1–62.1 months). Sixty-four patients developed recurrence, and 44 patients died. The median RFS (mRFS) was 6.0 months (95% CI 3.4–8.6 m), and the RFS for the radical resection group was longer than that for the non-radical resection group (9.5 vs. 5.3 m), with no significant difference (P > 0.05). The median OS (mOS) was 25.9 months (95% CI 14.4–37.4 m). The mOS was 24.6 months (95% CI 10.3–38.9 m) and 25.9 months (95% CI 10.9–40.9 m) in the non-radical resection group and the radical resection group, respectively. Multivariate Cox regression analysis showed that surgical approach, infiltration depth of the tumour, lymph node metastasis, and post-operative adjuvant therapy were independent risk factors for RFS and that post-operative adjuvant therapy was an independent risk factor for OS.Conclusion: By performing multivariate analysis, which corrected for potential confounding factors, we identified surgical procedures that were associated with RFS, and we found that RFS and OS in patients with vaginal melanoma and cervical melanoma benefitted from post-operative adjuvant therapy.

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Development and validation of a prognostic nomogram for lower-grade glioma based on an autophagy-related lncRNA signature

Archives of Medical Science ◽

10.5114/aoms/145435 ◽

2022 ◽

Author(s):

Jiazhe Lin ◽

Nuan Lin ◽

Wei-jiang Zhao

Keyword(s):

Proportional Hazards ◽

Cox Regression ◽

Cox Proportional Hazards ◽

Differentially Expressed ◽

Survival Prediction ◽

Lower Grade ◽

Lasso Regression ◽

Cox Proportional Hazards Regression ◽

Proportional Hazards Regression ◽

Kaplan Meier

IntroductionGliomas account for 75% of the primary malignant brain tumors. The prognosis and treatment planning vary in lower-grade gliomas (LGG) due to their heterogeneous clinical behaviors. The dysregulation of autophagy-related (ATG) lncRNAs plays a crucial role in LGG. We aimed to develop and validate an ATG lncRNA risk signature, and a survival nomogram with integration of novel prognostic for LGG patients.Material and methodsDifferentially expressed ATG lncRNAs were screened out based on TCGA and GTEx RNA-seq databases. ATG lncRNA prognostic signature was then established by Kaplan–Meier, univariate Cox proportional hazards regression, Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox proportional hazards regression, with its predictive value validated by time-dependent receiver operating characteristic (ROC) curves. Kaplan–Meier, univariate Cox regression and multivariate Cox proportional hazards regression were used to screen out clinical and molecular variables. A nomogram was developed and internally validated by ROC and calibration plots.ResultsAn ATG lncRNA risk signature was constructed with six differentially expressed lncRNAs (LINC00599, LINC02609, AC021739.2, AL118505.1, AL354892.2, and AL590666.2). Based on the risk signature, a nomogram was developed by addition of the significant prognostic clinical variables (age and grade) and molecular variables (IDH status and MGMT status).ConclusionsWe identified an ATG lncRNA risk signature and develop a nomogram for individualized survival prediction in LGG patients. A user-friendly free online calculator to facilitate the use of this nomogram among clinicians is also provided: https://linstu2009.shinyapps.io/LGGPRODICTORapp/?_ga=2.3154800.1506830296.1588641469-159983587.1588641469.

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Unplanned Reoperation After Trapeziometacarpal Arthroplasty: Rate, Reasons, and Risk Factors

Hand ◽

10.1177/1558944716679605 ◽

2016 ◽

Vol 12 (5) ◽

pp. 446-452 ◽

Cited By ~ 5

Author(s):

Suzanne C. Wilkens ◽

Zichao Xue ◽

Jos J. Mellema ◽

David Ring ◽

Neal Chen

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Regression ◽

Persistent Pain ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cox Regression Analysis ◽

Factors Associated ◽

Hazards Model ◽

Kaplan Meier

Background: Trapeziometacarpal (TMC) arthritis is an expected part of ageing to which most patients adapt well. Patients who do not adapt to TMC arthritis may be offered operative treatment. The factors associated with reoperation after TMC arthroplasty are incompletely understood. The purpose of this study was to determine the rate of, the underlying reasons for, and the factors associated with unplanned reoperation after TMC arthroplasty. Methods: In this retrospective study, we included all adult patients who had TMC arthroplasty for TMC arthritis at 1 of 3 large urban area hospitals between January 2000 and December 2009. Variables were inserted into a multivariable Cox proportional hazards model to determine factors associated with unplanned reoperation, and the Kaplan-Meier curve was used to estimate and describe the probability of unplanned reoperation over time. Results: Among 458 TMC arthroplasties, 19 (4%) had an unplanned reoperation; 16 of 19 (84%) for persistent pain and two-thirds within the first year. The multivariate Cox regression analysis showed that unplanned reoperation was independently associated with younger age, surgeon inexperience, and index procedure type. Conclusions: Surgeons should be aware as well as patients should be informed that as many as 4% are offered or request a second surgery, usually for persistent pain and often within the 1-year window when additional improvement is anticipated.

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Days Gained Response Discriminates Treatment Response in Patients with Recurrent Glioblastoma Receiving Bevacizumab-based Therapies

10.1101/752402 ◽

2019 ◽

Cited By ~ 1

Author(s):

Kyle W. Singleton ◽

Alyx B. Porter ◽

Leland S. Hu ◽

Sandra K Johnston ◽

Kamila M. Bond ◽

...

Keyword(s):

Treatment Response ◽

Proportional Hazards ◽

Cox Regression ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Recurrent Glioblastoma ◽

Response To Therapy ◽

Cytotoxic Therapy ◽

Kaplan Meier ◽

Recurrent Gbm

AbstractPurposeAccurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma multiforme (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze Days Gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies.Experimental DesignDays Gained response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N=62). Kaplan-Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM.ResultsIn patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan-Meier analysis showed significant differences in OS and PFS at previously identified DG cutoffs consistent with previous DG analyses using gadolinium-enhanced T1 weighted MR imaging. DG scores for bevacizumab monotherapy only approached significance for PFS. Cox regression showed that increases of 25 DG were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy.ConclusionDays Gained has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.

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