Associations of homocysteine metabolism with the risk of spinal osteoarthritis progression in postmenopausal women

Abstract Purpose Although homocysteine accumulation is a reported risk factor for several age-related disorders, little is known on its relationship with osteoarthritis (OA). We therefore investigated for associations of homocysteine and C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR), which is involved in homocysteine clearance, with the development and progression of spinal OA, through a combined cross-sectional and longitudinal cohort study. Methods A total of 1306 Japanese postmenopausal outpatients participating in the Nagano Cohort Study were followed for a 9.7-year mean period. Cross-sectional multiple logistic regression for spinal OA prevalence at registration by serum homocysteine level was performed with adjustment for confounders. In addition to Kaplan–Meier analysis, multivariate Cox regression was employed to examine the independent risk of MTHFR C677T variant for spinal OA progression. Results Multivariate regression analysis revealed a significant association between homocysteine and spinal OA prevalence (odds ratio 1.38; 95% confidence interval [CI] 1.14–1.68). Kaplan–Meier curves showed a gene dosage effect of the T allele in MTHFR C677T polymorphism on the accelerated progression of spinal OA severity (P = 0.003). A statistically significant independent risk of the T allele for spinal OA advancement was validated by Cox regression analysis. Respective adjusted hazard ratios for the CT/TT and TT genotypes were 1.68 (95% CI 1.16–2.42) and 1.67 (95% CI 1.23–2.28). Conclusions Circulating homocysteine and C677T variant in MTHFR are associated with the prevalence rate and ensuing progression, respectively, of spinal OA. These factors may represent potential interventional targets to prevent OA development and improve clinical outcomes.

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Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis

Journal of Oncology ◽

10.1155/2021/6646459 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Jianye Tan ◽

Haofeng Liang ◽

Bingsheng Yang ◽

Shuang Zhu ◽

Guofeng Wu ◽

...

Keyword(s):

Regression Analysis ◽

Cox Regression ◽

Survival Rates ◽

Prognostic Biomarkers ◽

Messenger Rnas ◽

Hub Genes ◽

Cox Regression Analysis ◽

Expression Levels ◽

Kaplan Meier ◽

Before And After

Osteosarcoma (OS) often occurs in children and often undergoes metastasis, resulting in lower survival rates. Information on the complexity and pathogenic mechanism of OS is limited, and thus, the development of treatments involving alternative molecular and genetic targets is hampered. We categorized transcriptome data into metastasis and nonmetastasis groups, and 400 differential RNAs (230 messenger RNAs (mRNAs) and 170 long noncoding RNAs (lncRNAs)) were obtained by the edgeR package. Prognostic genes were identified by performing univariate Cox regression analysis and the Kaplan–Meier (KM) survival analysis. We then examined the correlation between the expression level of prognostic lncRNAs and mRNAs. Furthermore, microRNAs (miRNAs) corresponding to the coexpression of lncRNA-mRNA was predicted, which was used to construct a competitive endogenous RNA (ceRNA) regulatory network. Finally, multivariate Cox proportional risk regression analysis was used to identify hub prognostic genes. Three hub prognostic genes (ABCG8, LOXL4, and PDE1B) were identified as potential prognostic biomarkers and therapeutic targets for OS. Furthermore, transcriptions factors (TFs) (DBP, ESX1, FOS, FOXI1, MEF2C, NFE2, and OTX2) and lncRNAs (RP11-357H14.16, RP11-284N8.3, and RP11-629G13.1) that were able to affect the expression levels of genes before and after transcription were found to regulate the prognostic hub genes. In addition, we identified drugs related to the prognostic hub genes, which may have potential clinical applications. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the expression levels of ABCG8, LOXL4, and PDE1B coincided with the results of bioinformatics analysis. Moreover, the relationship between the hub prognostic gene expression and patient prognosis was also validated. Our study elucidated the roles of three novel prognostic biomarkers in the pathogenesis of OS as well as presenting a potential clinical treatment for OS.

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Predictive Value of Atrial Electromechanical Delay on Long-Term Cardiovascular Outcomes in Hemodialysis Patients

American Journal of Nephrology ◽

10.1159/000441099 ◽

2015 ◽

Vol 42 (3) ◽

pp. 239-249 ◽

Cited By ~ 2

Author(s):

Kultigin Turkmen ◽

Levent Demirtas ◽

Ergun Topal ◽

Abduzhappar Gaipov ◽

Ismail Kocyigit ◽

...

Keyword(s):

Regression Analysis ◽

Total Cholesterol ◽

Cox Regression ◽

Healthy Individuals ◽

Electromechanical Delay ◽

Cox Regression Analysis ◽

Atrial Electromechanical Delay ◽

Kaplan Meier ◽

All Cause Mortality ◽

Spearman Test

Background: Atrial electromechanical delay (AEMD) times were considered independent predictors of cardiovascular morbidity among the general population. We aimed at evaluating AEMD times and other risk factors associated with 2-year combined cardiovascular (CV) events in HD patients. Material and Methods: Sixty hemodialysis (HD) and 44 healthy individuals were enrolled in this prospective study. Echocardiography was performed before the mid-week dialysis session for HD patients. Data were expressed as mean ± SD. Spearman test was used to assess linear associations. Survival was examined with the Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the predictors of combined CV events in this cohort. Results: At the beginning of the study, left intra-atrial-AEMD times were significantly longer in HD patients compared to the left intra-atrial-AEMD times in healthy individuals. After 24 months, 41 patients were still on HD treatment and 19 (31.6%) had died. Serum triglyceride, total cholesterol and albumin were found to be higher and C-reactive protein (CRP) levels, left intra-atrial EMD time (LIAT) and interatrial EMD times were found to be lower in survived HD patients. With the cut-off median values of 3.5 g/dl for albumin, 0.87 mg/dl for CRP, 157 mg/dl for total cholesterol and 151 mg/dl for triglyceride, the Kaplan-Meier curves demonstrated significant differences in terms of all-cause mortality. We also demonstrated the Kaplan-Meier survival curves of HD patients according to tertile values of LIAT. Cox regression analysis revealed that increased CRP and higher LIAT were found to be independent predictors of combined CV events. Conclusions: Increased LIAT and inflammation were found to be closely associated with 2 years combined CV events and all-cause mortality in HD patients.

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Association of masseter area and radiodensity with three-month survival after proximal anterior circulation occlusion

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2020-015837 ◽

2020 ◽

Vol 13 (1) ◽

pp. 25-29 ◽

Cited By ~ 1

Author(s):

Iisa Lindström ◽

Sara Protto ◽

Niina Khan ◽

Jussi Hernesniemi ◽

Niko Sillanpää ◽

...

Keyword(s):

Regression Analysis ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Cox Regression ◽

Multivariable Logistic Regression Analysis ◽

Anterior Circulation ◽

Term Survival ◽

Cox Regression Analysis ◽

Kaplan Meier

BackgroundMasseter area (MA), a surrogate for sarcopenia, appears to be useful when estimating postoperative survival, but there is lack of consensus regarding the potential predictive value of sarcopenia in acute ischemic stroke (AIS) patients. We hypothesized that MA and density (MD) evaluated from pre-interventional CT angiography scans predict postinterventional survival in patients undergoing mechanical thrombectomy (MT).Materials and methods312 patients treated with MT for acute occlusions of the internal carotid artery (ICA) or the M1 segment of the middle cerebral artery (M1-MCA) between 2013 and 2018. Median follow-up was 27.4 months (range 0–70.4). Binary logistic (alive at 3 months, OR <1) and Cox regression analyses were used to study the effect of MA and MD averages (MAavg and MDavg) on survival.ResultsIn Kaplan–Meier analysis, there was a significant inverse relationship with both MDavg and MAavg and mortality (MDavg P<0.001, MAavg P=0.002). Long-term mortality was 19.6% (n=61) and 3-month mortality 12.2% (n=38). In multivariable logistic regression analysis at 3 months, per 1-SD increase MDavg (OR 0.61, 95% CI 0.41 to 0.92, P=0.018:) and MAavg (OR 0.57, 95% CI 0.35 to 0.91, P=0.019) were the independent predictors associated with lower mortality. In Cox regression analysis, MDavg and MAavg were not associated with long-term survival.ConclusionsIn acute ischemic stroke patients, MDavg and MAavg are independent predictors of 3-month survival after MT of the ICA or M1-MCA. A 1-SD increase in MDavg and MAavg was associated with a 39%–43% decrease in the probability of death during the first 3 months after MT.

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Prognostic value of D-dimer/fibrinogen ratio in the adverse outcomes of patients hospitalized for heart failure

Biomarkers in Medicine ◽

10.2217/bmm-2020-0553 ◽

2020 ◽

Vol 14 (18) ◽

pp. 1733-1745

Author(s):

Tian-Jun Zhao ◽

Qian-Kun Yang ◽

Chun-Yu Tan ◽

Li-Dan Bi ◽

Jie Li ◽

...

Keyword(s):

Heart Failure ◽

Regression Analysis ◽

Cox Regression ◽

Prognostic Indicator ◽

Adverse Outcomes ◽

Rank Test ◽

Clinical Value ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

D Dimer

Aim: To evaluate the clinical value of plasma D-dimer/fibrinogen ratio (DFR) in patients hospitalized for heart failure (HF). Methods: Clinical data of 235 patients were retrospectively analyzed. Kaplan–Meier method and Cox regression analysis were used to identify significant prognosticators. Results: The Kaplan–Meier analysis showed that a higher DFR level was significantly associated with an increase in the end point outcomes, including HF readmission, thrombotic events and death (log-rank test: p < 0.001). The multivariate Cox regression analysis showed that the high tertile of DFR was significantly associated with the study end points (HR: 2.18; 95% CI: 1.31–3.62; p = 0.003), compared with the low tertile. Conclusion: DFR is a reliable prognostic indicator for patients hospitalized for HF.

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Comparison of 24-hour and Office Pulse Wave Velocity for Prediction of Mortality in Hemodialysis Patients

American Journal of Nephrology ◽

10.1159/000499532 ◽

2019 ◽

Vol 49 (4) ◽

pp. 317-327 ◽

Cited By ~ 10

Author(s):

Julia Matschkal ◽

Christopher C. Mayer ◽

Pantelis A. Sarafidis ◽

Georg Lorenz ◽

Matthias C. Braunisch ◽

...

Keyword(s):

Regression Analysis ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Cardiovascular Mortality ◽

Pulse Wave ◽

Cox Regression ◽

Hemodialysis Patients ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

All Cause Mortality

Background: Mortality in hemodialysis patients still remains unacceptably high. Enhanced arterial stiffness is a known cardiovascular risk factor, and pulse wave velocity (PWV) has proven to be a valid parameter to quantify risk. Recent studies showed controversial results regarding the prognostic significance of PWV for mortality in hemodialysis patients, which may be due to methodological issues, such as assessment of PWV in the office setting (Office-PWV). Method: This study cohort contains patients from the “Risk stratification in end-stage renal disease – the ISAR study,” a multicenter prospective longitudinal observatory cohort study. We examined and compared the predictive value of ambulatory 24-hour PWV (24 h-PWV) and Office-PWV on mortality in a total of 344 hemodialysis patients. The endpoints of the study were all-cause and cardiovascular mortality. Survival analysis included Kaplan-Meier estimates and Cox regression analysis. Results: During a follow-up of 36 months, a total of 89 patients died, 35 patients due to cardiovascular cause. Kaplan-Meier estimates for tertiles of 24 h-PWV and Office-PWV were similarly associated with mortality. In univariate Cox regression analysis, 24 h-PWV and Office-PWV were equivalent predictors for all-cause and cardiovascular mortality. After adjustment for common risk factors, only 24 h-PWV remained solely predictive for all-cause mortality (hazard ratio 2.51 [95% CI 1.31–4.81]; p = 0.004). Conclusions: Comparing both measurements, 24 h-PWV is an independent predictor for all-cause-mortality in hemodialysis patients beyond Office-PWV.

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Predicting Acute Malnutrition in Rural Twins Before Their Second Birthday: Cohort Study

Current Developments in Nutrition ◽

10.1093/cdn/nzaa061_034 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1406-1406

Author(s):

Franck Garanet

Keyword(s):

Regression Analysis ◽

Cohort Study ◽

Cox Regression ◽

Dietary Supplementation ◽

Acute Malnutrition ◽

P Value ◽

Cox Regression Analysis ◽

Funding Sources ◽

Significance Threshold ◽

Wealthy Household

Abstract Objectives Identify the predictors of acute malnutrition in rural twins in a context of dietary supplementation in Burkina Faso. Methods This is a prospective cohort study. A cox regression was used to investigate predictors of acute malnutrition. A significance threshold of 0.05 was considered. Results Severe acute malnutria was more common in twins compared to non-twins (22.13% vs. 9.98%, P-0.001). Growth retardation was more common in twins compared to non-twins (34.04% vs. 21.49%, P-0.001). Underweight was more common in twins compared to non-twins (1.70% versus 0.43%). This difference was not statically significant (P-0.06). In multi-varied cox regression analysis, the factors significantly associated with acute malnutrition were: being born twins, episodes of fevers, diarrhea, and wealth level. Twins were almost twice as likely to be malnourished compared to single children (HRa −1.82, IC95% - [1.59–2.07] and P-0.001). Children with a fever were 2.54 more likely to be malnourished than other children. (HRa - 2.15, IC95% - [1.74–2.67] and P-0.001). Children with diarrhea were 2.54 more likely to be malnourished than other children. (HRa - 2.05, IC95% - [1.62–2.59] and P-0.001). Children born in a wealthy household were 25% less likely to be malnourished compared to other children (HRa-0.75; IC95%, [0.61–0.92]; P-value-0.007). Conclusions Particular attention should be paid to twins, in order to reduce the risk of acute malnutrition before their second birthday. Funding Sources None.

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Hyperuricemia and Impaired Renal Function: A Prospective Cohort Study

Kidney Diseases ◽

10.1159/000511196 ◽

2020 ◽

pp. 1-9

Author(s):

Noppawit Aiumtrakul ◽

Puvanant Wiputhanuphongs ◽

Ouppatham Supasyndh ◽

Bancha Satirapoj

Keyword(s):

Renal Function ◽

Uric Acid ◽

Regression Analysis ◽

Cohort Study ◽

Serum Uric Acid ◽

Prospective Cohort ◽

Impaired Renal Function ◽

Cox Regression ◽

Community Based ◽

Cox Regression Analysis

Background: Related studies have demonstrated a relationship of elevated serum uric levels with a decline in kidney function. However, limited evidence exists in a Southeast Asian community-based population. Objective: The study aimed to examine the relationship between serum uric acid levels and impaired renal function. Methods: A prospective cohort study was conducted in the Thai army health checkup population between July 1, 2006 and December 31, 2012. Inclusion criteria included age older than 20 years and baseline estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73 m2. Cox regression analysis was used to evaluate the association between incidence of impaired renal function and baseline serum uric acid quartiles. Impaired renal function was defined as eGFR <60 mL/min/1.73 m2 over 3 months. Results: A total of 9,534 participants (7,474 men and 2,060 women) were enrolled. Cox regression analysis revealed a significant association of serum uric acid level with impaired renal function in the whole population as the unadjusted hazard ratio (HR) (95% CI) of impaired renal function in second, third, and fourth quartiles were 2.1 (1.39, 3.17), 2.39 (1.6, 3.59), and 3.94 (2.71, 5.74), respectively, when compared with serum uric acid in the first quartile, respectively. After adjusting in 2 models, the HR still significantly persisted with similar magnitudes in all quartiles. Higher incidences of impaired renal function were observed among males than among females in all quartiles. Kaplan-Meier curve showed better renal survival rate in the lower quartile groups. Linear regression analysis showed that eGFR negatively correlated with serum uric acid (r = −0.213, p < 0.001). Conclusion: Our study suggests that an independent association exists of serum uric acid levels with the incidence of impaired renal function and renal progression in the Southeast Asian community-based population.

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P1166DOES PERITONEAL PROTEIN LOSS AFFECT CARDIOVASCULAR MORTALITY OF PERITONEAL DIALYSIS PATIENTS ?

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1166 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Marios Theodoridis ◽

Stylianos Panagoutsos ◽

Ioannis Neofytou ◽

Konstantia Kantartzi ◽

Efthimia Mourvati ◽

...

Keyword(s):

Regression Analysis ◽

Peritoneal Dialysis ◽

Cardiovascular Mortality ◽

Cox Regression ◽

Dialysis Patients ◽

Protein Loss ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Group A ◽

Group B

Abstract Background and Aims Peritoneal protein loss (PPL) through peritoneal effluent has been a well-recognized detrimental result of peritoneal dialysis (PD). The amount of protein lost will depend on dialysis time, protein size, its serum concentration and other factors including patients’ clinical status. Peritoneal protein loss may be a manifestation of endothelial dysfunction, as with another type of capillary protein leakage, microalbuminuria, a recognized endothelial dysfunction marker. The aim of this study was to retrospectively evaluate the influence of PPL on cardiovascular mortality of peritoneal dialysis patients Method This is a single center retrospective study of 84 PD patients (m=54, f=30) with mean age of 65.2±17 years, mean PD duration of 43.2±24.9 months conducted for the time period from 2006 to 2019 (13 years). The patients were divided into two groups according to the amount of protein excreted during the modified Peritoneal Equilibration Test (PET) procedure using PD solution of 3.86% DW, 2 Lt infusion volume for total time of 4 hours. The total amount of proteins excreted was calculate from PET by multiplying the concentration of proteins at the end of the test with the total volume of PD fluid at the same time. Group A excreted a total amount of proteins < 1.55 gr (median value) at the end of PET test and Group B > 1.55 gr. The cumulative all-cause and cardiovascular survival of the PD patients was calculated by Kaplan Meier while the possible effect of any parameter in survival rates was evaluated by using Cox Regression analysis Results There was not any statistically significant difference between the two groups according to PD duration, age, dialysis adequacy targets, Residual Renal Function(RRF), BMI, ultrafiltration volume during PET and their transport status. The cumulative all-cause survival using Kaplan-Meier analysis revealed no statistically significant deference between the two groups (Log Rank p=0.55) even though mortality risk was adjusted for several factors (Cox Regression). When cardiovascular survival, using Cox Regression analysis, was adjusted for age, sex, Diabetes, PD modality, dialysis Kt/V and RRF we found that Group A (with protein excretion < 1.55 gr) had statistically significant better cardiovascular survival (p=0.029) compared to Group B. We confirm these results while trying to find among the total of our patients the possible risk factors for cardiovascular mortality. Using Cox Regression analysis, the amount of protein excreted during PET procedure and the type of PD solutions (high or low in GDPs) used were statistically significant (p=0.019 and p=0.04 respectively) independent risk factors for cardiovascular survival in our patients. Conclusion These results indicate that protein loss during peritoneal dialysis procedure has negative impact on cardiovascular mortality and survival of PD patients. Additionally, the use of PD solutions with low Glucose Degradation Products (GDPs) and AGEs may improve PD patient’s cardiovascular survival. Randomized interventional studies are encouraged to address the pathological concern of PPL in the future, namely its effects on cardiovascular conditions or its role as marker and effort to reduce PPL using ACE inhibitors or vit D should be considered only if it diminishes cardiovascular morbidity or mortality.

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Abnormal Serum Free Light Chain Ratios Are Associated with Earlier Time to First Treatment and Poor Survival in Patients with Chronic Lymphocytic Leukaemia

Blood ◽

10.1182/blood.v112.11.3141.3141 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3141-3141

Author(s):

Guy Pratt ◽

Graham Mead ◽

Supratik Basu ◽

Abe Jacobs ◽

Roger Holder ◽

...

Keyword(s):

Regression Analysis ◽

Cox Regression ◽

Prognostic Significance ◽

Lymphocytic Leukemia ◽

Female Ratio ◽

Cox Regression Analysis ◽

Serum Free ◽

Kaplan Meier ◽

Mutational Status ◽

Time To First Treatment

Abstract Introduction: Serum free light chains (sFLC) have prognostic significance in plasma cell disorders. In B-cell chronic lymphocytic leukemia (CLL), a small study found 8/18 (44%) of patients to have abnormal FLC ratios but no assessment of prognostic value was published. The aim of the present study was to determine whether abnormal serum FLC concentrations are indicative of a poor prognosis in CLL patients. Methods: Sera were analysed from 381 previously diagnosed CLL patients (Stage A 307; B 30; C 26; 18 missing; male: Female Ratio 1.6:1, mean age 71 (29–98)) with samples taken before their first treatment (303) or after treatment (78). The study was approved by the Birmingham Heart of England NHS Trust Review Board. Patients were described using the Binet staging system and measured for prognostic markers including CD38, Zap70, mutational status, β2M and FLC. Kaplan Meier survival curves and Cox proportional hazards regression (age, sex, CD38, Zap 70, mutational status, β2M and sFLC) were calculated using SPSS v14. Results: 147/381 (39%) patient sera had abnormal sFLC ratios. Kaplan Meier analysis of all deaths showed abnormal ratios were significantly associated with worse survival (n=350, p<0.001). Analysis of deaths attributed to CLL (n=30) also indicated that an abnormal FLC ratio was predictive of shorter survival (p=0.001). However, for deaths not attributed to CLL (n=32), the FLC ratio was not significantly predictive of outcome (p=0.112). For Cox regression analysis (n=228) of deaths attributed to CLL only, three significant, independent, prognostic factors were identified: CD38 (p<0.001), abnormal ratio (p<0.001) and Stage (p=0.027). Analysis of the untreated patient population (n=303), using Kaplan Meier analysis of time to first treatment, found that an abnormal lambda ratio (p=0.04) but not an abnormal kappa ratio (p=0.443) predicted earlier treatment. For patients with an abnormal lambda ratio, the mean time to first treatment was 38 months earlier than those patients with a normal ratio. Cox regression analysis (n=171) of time to first treatment, found 4 significant, independent factors predicting earlier treatment: Zap70 (p<0.001), Age (p<0.001), abnormal sFLC ratio (p=0.001) and Stage (p=0.027). Conclusions: As shown in other monoclonal gammopathies, abnormal sFLC ratios were associated with poorer outcomes in patients with CLL. Furthermore, in an untreated population, patients with an abnormal lambda sFLC ratio required earlier treatment, indicating a pathological mechanism which is as yet unclear but which warrants further investigation.

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