Associations of Serum Total Bilirubin with Survival Outcomes in Patients with Cancer Cachexia: A Retrospective, Multicenter Cohort Study

Abstract Background: Cancer cachexia is a systemic paraneoplastic phenomenon involving multiple organs, including the liver. Total bilirubin (TBIL) is an easily obtained blood biomarker that reflects liver homeostasis. This work evaluated the prognostic value of serum TBIL in patients with cancer cachexia.Methods: This study included 2,282 patients from a multicenter research database who were diagnosed with cancer cachexia between June 2012 and December 2019. The hazard ratio (HR) for all-cause mortality was analyzed using Cox proportional hazards regression models. The association of serum TBIL with all-cause mortality was modeled with restricted cubic splines. The optimal cutoff value for TBIL was calculated with maximally selected rank statistics.Results: Among the participants, there were 1,327 (58.2%) males and 955 (41.8%) females. The mean patient age was 60.4±1.5 years. The 12-month all-cause mortality rate for patients with cancer cachexia was 29.5% (95% CI: 27.6%-31.3%), resulting in a rate of 209.58 events per 1000 patient-years. An inverted L-shaped association between TBIL and all-cause mortality was observed. The cutoff point for TBIL for the prediction of the time to mortality was < 21.7 µmol/L. A high TBIL level but not the direct bilirubin (DBIL) or indirect bilirubin (IBIL) level was identified as an independent prognostic factor (HR, 1.60, 95% CI, 1.32-1.93). For patients with digestive system tumors, a high serum TBIL level (≥21.7 µmol/L) was significantly associated with mortality. Conclusion: High TBIL levels are associated with increased all-cause mortality in patients and might be a promising prognostic indicator in patients with cancer cachexia.

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Baseline Serum Bilirubin and Risk of First Stroke in Hypertensive Patients

Journal of the American Heart Association ◽

10.1161/jaha.119.015799 ◽

2020 ◽

Vol 9 (12) ◽

Author(s):

Jiancheng Wang ◽

Xianglin Zhang ◽

Zhuxian Zhang ◽

Yuanyuan Zhang ◽

Jingping Zhang ◽

...

Keyword(s):

Ischemic Stroke ◽

Proportional Hazards ◽

Total Bilirubin ◽

Serum Bilirubin ◽

Cox Proportional Hazards ◽

Direct Bilirubin ◽

Serum Total Bilirubin ◽

Inverse Association ◽

Baseline Serum ◽

Hypertensive Patients

Background Data on the association between serum bilirubin and the risk of stroke are limited and inconclusive. We aimed to evaluate the association between serum bilirubin and the risk of first stroke and to examine any possible effect modifiers in hypertensive patients. Methods and Results Our study was a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). A total of 19 906 hypertensive patients were included in the final analysis. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for the risk of first stroke associated with serum bilirubin levels. The median follow‐up period was 4.5 years. When serum total bilirubin was assessed as tertiles, the adjusted HR of first ischemic stroke for participants in tertile 3 (12.9–34.1 μmol/L) was 0.75 (95% CI, 0.59–0.96), compared with participants in tertile 1 (<9.3 μmol/L). When direct bilirubin was assessed as tertiles, a significantly lower risk of first ischemic stroke was also found in participants in tertile 3 (2.5–24.8 μmol/L) (adjusted HR, 0.77; 95% CI, 0.60–0.98), compared with those in tertile 1 (<1.6 μmol/L). However, there was no significant association between serum total bilirubin (tertile 3 versus 1: adjusted HR, 1.45; 95% CI, 0.89–2.35) or direct bilirubin (tertile 3 versus 1: adjusted HR, 1.27; 95% CI, 0.76–2.11) and first hemorrhagic stroke. Conclusions In this sample of Chinese hypertensive patients, there was a significant inverse association between serum total bilirubin or direct bilirubin and the risk of first ischemic stroke.

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Nonlinear relationship between serum total bilirubin levels and initial ischemic stroke in patients with non-valvular atrial fibrillation

Journal of International Medical Research ◽

10.1177/0300060520962347 ◽

2020 ◽

Vol 48 (10) ◽

pp. 030006052096234

Author(s):

Ying Liu ◽

Jie Wang ◽

Wen-zhen Zeng ◽

Qing-shan Lyu

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Proportional Hazards ◽

Total Bilirubin ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Serum Total Bilirubin ◽

Hazards Model

Objective This study aimed to examine the relationship between total bilirubin levels and initial ischemic stroke in patients with non-valvular atrial fibrillation. Methods This was a retrospective study. Atrial fibrillation was diagnosed by 24-hour Holter electrocardiography and serum total bilirubin levels were divided into quintiles. Ischemic stroke was diagnosed by symptoms, signs, and a medical image examination. The multivariate Cox proportional hazards model and survival analysis were used to estimate the association of total bilirubin with initial ischemic stroke. Results We studied 316 patients with non-valvular atrial fibrillation. During follow-up, there were 42 (13.29%) first ischemic strokes. After multivariate adjustment, for each 1 µmol/L increase in total bilirubin, the risk of first ischemic stroke increased by 4% (95% confidence interval [CI]: 1.01, 1.07). When using the first quintile as the reference, from the second to fifth quintiles, the risks of first ischemic stroke were 0.52 (95% CI: 0.17, 1.65), 0.23 (95% CI: 0.06, 0.87), 0.92 (95% CI: 0.32, 2.67), and 1.33 (95% CI: 1.09, 4.41), respectively. The optimal cut-off point of total bilirubin for the lowest risk of ischemic stroke was 17.0 µmol/L. Conclusions Total bilirubin levels are nonlinearly associated with initial ischemic stroke in patients with non-valvular atrial fibrillation.

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Association Between the Change in Total Bilirubin and Risk of Bleeding Among Patients With Nonvalvular Atrial Fibrillation Taking Dabigatran

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620910808 ◽

2020 ◽

Vol 26 ◽

pp. 107602962091080

Author(s):

Yurong Xiong ◽

Lihua Hu ◽

Wei Zhou ◽

Minghui Li ◽

Tao Wang ◽

...

Keyword(s):

Proportional Hazards ◽

Total Bilirubin ◽

Cox Proportional Hazards ◽

Serum Total Bilirubin ◽

Bleeding Events ◽

Nonvalvular Atrial Fibrillation ◽

Risk Of Bleeding ◽

Cox Proportional Hazards Regression ◽

Proportional Hazards Regression

There is still a lack of effective biomarkers for the prediction of the risk of bleeding events among patients with nonvalvular atrial fibrillation (NVAF) taking dabigatran. This study aimed to investigate the association between change in total bilirubin (CTBIL) and risk of bleeding among patients with NVAF taking dabigatran. The CTBIL was the difference in serum total bilirubin at out of follow-up from baseline serum total bilirubin. A total of 486 patients with NVAF treated with dabigatran (110 mg twice daily) were recruited from 12 centers in China from February 2015 to December 2017. All patients were followed for 3 months. Cox proportional hazards regression analysis was used to evaluate the association between the CTBIL and bleeding. Moreover, a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (the penalized spline method) and 2 piecewise Cox proportional hazards models were used to address the nonlinearity between CTBIL and bleeding. The mean (SD) follow-up duration was 81.2 (20.2) days. In all, 67 patients experienced bleeding events. A U-shaped association was observed between the CTBIL and bleeding, with increased hazard ratios (HRs) in relation to either low or high CTBIL levels. For CTBIL <6.63 µmol/L, the HR (95% confidence interval [CI]) was 0.90 (0.84-0.96), and for CTBIL ≥6.63 µmol/L, the HR (95% CI) was 1.35 (1.14-1.60). Our findings showed a U-shaped relationship between CTBIL and bleeding. Both low and high levels of CTBIL were associated with a higher risk of bleeding.

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PARADOXICAL ASSOCIATION OF ADIPONECTIN WITH MORTALITY AMONG LONG-LIVED INDIVIDUALS AND THEIR OFFSPRING

Innovation in Aging ◽

10.1093/geroni/igz038.1791 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S481-S482

Author(s):

Iva Miljkovic ◽

Robert M Boudreau ◽

Ping An ◽

Bharat Thyagarajan ◽

Kaare Christensen ◽

...

Keyword(s):

Healthy Aging ◽

Proportional Hazards ◽

Biological Properties ◽

Cox Proportional Hazards ◽

Study Entry ◽

Serum Adiponectin ◽

Multicenter Cohort Study ◽

Cox Proportional Hazards Models ◽

All Cause Mortality ◽

Metabolic Properties

Abstract Adiponectin is an adipokine with well-recognized roles as an insulin-sensitizing, anti-inflammatory, and cardioprotective factor. Despite these biological properties, higher circulating adiponectin levels have recently emerged as a potential risk factor for mortality among older adults. We evaluated the relationship between adiponectin and all-cause mortality further using data collected on 3525 men and women who were participants in the Long Life Family Study (LLFS), a multicenter cohort study of two-generation families with a clustering of healthy aging and exceptional survival. Fasting serum adiponectin levels were measured at study entry. Date of death was abstracted from death certificates and proxy. Cox proportional hazards models were used to estimate the risk of mortality per one SD increase in adiponectin. We adjusted for age, sex, field center, education, lifestyle factors, BMI, comorbid conditions (diabetes, hypertension, lung diseases, heart disease, stroke, and cancer) and intra-familial correlation structure. The mean age of participants at study entry was 71.7 ± 16.3 years (range, 32-110 years; 44.4% male). A total of 1147 deaths occurred during an average 11 years of follow-up (25295 person-years). Higher serum adiponectin was associated with increased mortality even after adjusting for several potential confounding factors (Hazard ratio [95% CI]: 1.19 [1.12, 1.27]; P<0.0001). Consistent with prior studies and contrary to its beneficial metabolic properties, higher adiponectin level was associated with greater all-cause mortality among long-lived individuals and their offspring. Further studies are needed to assess the potential mechanisms underlying this paradoxical association.

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High School Quality and 56-Year All-Cause Mortality Risk Across Race and Ethnicity

Innovation in Aging ◽

10.1093/geroni/igaa057.1632 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 505-506

Author(s):

Dominika Seblova ◽

Kelly Peters ◽

Susan Lapham ◽

Laura Zahodne ◽

Tara Gruenewald ◽

...

Keyword(s):

High School ◽

Mortality Risk ◽

Race And Ethnicity ◽

Proportional Hazards ◽

School Quality ◽

Cox Proportional Hazards ◽

School Level ◽

Lower Mortality ◽

All Cause Mortality ◽

Race Ethnicity

Abstract Having more years of education is independently associated with lower mortality, but it is unclear whether other attributes of schooling matter. We examined the association of high school quality and all-cause mortality across race/ethnicity. In 1960, about 5% of US high schools participated in Project Talent (PT), which collected information about students and their schools. Over 21,000 PT respondents were followed for mortality into their eighth decade of life using the National Death Index. A school quality factor, capturing term length, class size, and teacher qualifications, was used as the main predictor. First, we estimated overall and sex-stratified Cox proportional hazards models with standard errors clustered at the school level, adjusting for age, sex, composite measure of parental socioeconomic status, and 1960 cognitive ability. Second, we added an interaction between school quality and race/ethnicity. Among this diverse cohort (60% non-Hispanic Whites, 23% non-Hispanic Blacks, 7% Hispanics, 10% classified as another race/s) there were 3,476 deaths (16.5%). School quality was highest for Hispanic respondents and lowest for non-Hispanic Blacks. Non-Hispanic Blacks also had the highest mortality risk. In the whole sample, school quality was not associated with mortality risk. However, higher school quality was associated with lower mortality among those classified as another race/s (HR 0.75, 95% CI: 0.56-0.99). For non-Hispanic Blacks and Whites, the HR point estimates were unreliable, but suggest that higher school quality is associated with increased mortality. Future work will disentangle these differences in association of school quality across race/ethnicity and examine cause-specific mortality.

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Associated characteristics and treatment outcomes of medication-related osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases

Supportive Care in Cancer ◽

10.1007/s00520-021-06018-x ◽

2021 ◽

Author(s):

Hiroaki Ikesue ◽

Moe Mouri ◽

Hideaki Tomita ◽

Masaki Hirabatake ◽

Mai Ikemura ◽

...

Keyword(s):

Zoledronic Acid ◽

Bone Metastases ◽

Tooth Extraction ◽

Proportional Hazards ◽

Osteonecrosis Of The Jaw ◽

Cox Proportional Hazards ◽

Patients With Cancer ◽

Proportional Hazards Regression ◽

Before And After ◽

Denosumab Treatment

Abstract Purpose This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ. Methods The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline. Results Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024). Conclusion The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.

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The incidence of mental disorder increases after hip fracture in older people: a nationwide cohort study

BMC Geriatrics ◽

10.1186/s12877-021-02195-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ling-Yin Kuo ◽

Po-Ting Hsu ◽

Wen-Tien Wu ◽

Ru-Ping Lee ◽

Jen-Hung Wang ◽

...

Keyword(s):

Cohort Study ◽

Hip Fracture ◽

Geriatric Patients ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Control Group ◽

Research Database ◽

Fracture Group ◽

Related Risk ◽

And Control

Abstract Background People living with dementia seem to be more likely to experience delirium following hip fracture. The association between mental disorders (MD) and hip fracture remains controversial. We conducted a nationwide study to examine the prevalence of MD in geriatric patients with hip fractures undergoing surgery and conducted a related risk factor analysis. Material and methods This retrospective cohort study used data from Taiwan’s National Health Insurance Research Database between 2000 and 2012 and focused on people who were older than 60 years. Patients with hip fracture undergoing surgical intervention and without hip fracture were matched at a ratio of 1:1 for age, sex, comorbidities, and index year. The incidence and hazard ratios of age, sex, and multiple comorbidities related to MD and its subgroups were calculated using Cox proportional hazards regression models. Results A total of 1408 patients in the hip fracture group and a total of 1408 patients in the control group (no fracture) were included. The overall incidence of MD for the hip fracture and control groups per 100 person-years were 0.8 and 0.5, respectively. Among MD, the incidences of transient MD, depression, and dementia were significantly higher in the hip fracture group than in the control group. Conclusions The prevalence of newly developed MD, especially transient MD, depression, and dementia, was higher in the geriatric patients with hip fracture undergoing surgery than that in the control group. Prompt and aggressive prevention protocols and persistent follow-up of MD development is highly necessary in this aged society.

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Association of mushroom consumption with all-cause and cause-specific mortality among American adults: prospective cohort study findings from NHANES III

Nutrition Journal ◽

10.1186/s12937-021-00691-8 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Djibril M. Ba ◽

Xiang Gao ◽

Joshua Muscat ◽

Laila Al-Shaar ◽

Vernon Chinchilli ◽

...

Keyword(s):

Lower Risk ◽

Proportional Hazards ◽

Total Mortality ◽

Cox Proportional Hazards ◽

Dietary Factors ◽

Mortality Data ◽

Nhanes Iii ◽

Dietary Recall ◽

All Cause Mortality ◽

Specific Mortality

Abstract Background Whether mushroom consumption, which is rich in several bioactive compounds, including the crucial antioxidants ergothioneine and glutathione, is inversely associated with low all-cause and cause-specific mortality remains uncertain. This study aimed to prospectively investigate the association between mushroom consumption and all-cause and cause-specific mortality risk. Methods Longitudinal analyses of participants from the Third National Health and Nutrition Examination Survey (NHANES III) extant data (1988–1994). Mushroom intake was assessed by a single 24-h dietary recall using the US Department of Agriculture food codes for recipe foods. All-cause and cause-specific mortality were assessed in all participants linked to the National Death Index mortality data (1988–2015). We used Cox proportional hazards regression models to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cause-specific mortality. Results Among 15,546 participants included in the current analysis, the mean (SE) age was 44.3 (0.5) years. During a mean (SD) follow-up duration of 19.5 (7.4) years , a total of 5826 deaths were documented. Participants who reported consuming mushrooms had lower risk of all-cause mortality compared with those without mushroom intake (adjusted hazard ratio (HR) = 0.84; 95% CI: 0.73–0.98) after adjusting for demographic, major lifestyle factors, overall diet quality, and other dietary factors including total energy. When cause-specific mortality was examined, we did not observe any statistically significant associations with mushroom consumption. Consuming 1-serving of mushrooms per day instead of 1-serving of processed or red meats was associated with lower risk of all-cause mortality (adjusted HR = 0.65; 95% CI: 0.50–0.84). We also observed a dose-response relationship between higher mushroom consumption and lower risk of all-cause mortality (P-trend = 0.03). Conclusion Mushroom consumption was associated with a lower risk of total mortality in this nationally representative sample of US adults.

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Elevated Serum Trimethylamine N-Oxide Levels Are Associated with Mortality in Male Patients on Peritoneal Dialysis

Blood Purification ◽

10.1159/000512962 ◽

2021 ◽

pp. 1-11

Author(s):

Dongying Fu ◽

Jiani Shen ◽

Wei Li ◽

Yating Wang ◽

Zhong Zhong ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Proportional Hazards ◽

Elevated Serum ◽

Ultra Performance Liquid Chromatography ◽

Cox Proportional Hazards ◽

Serum Samples ◽

Entire Cohort ◽

Increased Risk ◽

All Cause Mortality ◽

Male Patients

Background: Elevated levels of serum trimethylamine N-oxide (TMAO) have been previously linked to adverse cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the clinical significance of serum TMAO levels in patients treated with peritoneal dialysis (PD) is unclear. Methods: A total of 1,032 PD patients with stored serum samples at baseline were enrolled in this prospective study. Serum concentrations of TMAO were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. Cox proportional hazards and competing-risk regression models were performed to examine the association of TMAO levels with all-cause and CV mortality. Results: The median level of serum TMAO in our study population was 34.5 (interquartile range (IQR), 19.8–61.0) μM. During a median follow-up of 63.7 months (IQR, 43.9–87.2), 245 (24%) patients died, with 129 (53%) deaths resulting from CV disease. In the entire cohort, we observed an association between elevated serum TMAO levels and all-cause mortality (adjusted subdistributional hazard ratio [SHR], 1.22; 95% confidence interval [95% CI], 1.01–1.48; p = 0.039) but not CV mortality. Further analysis revealed such association differed by sex; the elevation of serum TMAO levels was independently associated with increased risk of both all-cause (SHR, 1.37; 95% CI, 1.07–1.76; p = 0.013) and CV mortality (SHR, 1.41; 95% CI, 1.02–1.94; p = 0.038) in men but not in women. Conclusions: Higher serum TMAO levels were independently associated with all-cause and CV mortality in male patients treated with PD.

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The association between triglyceride-glucose index, cardio-cerebrovascular diseases, and death in Korean adults: A retrospective study based on the NHIS-HEALS cohort

PLoS ONE ◽

10.1371/journal.pone.0259212 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0259212

Author(s):

Joungyoun Kim ◽

Sang-Jun Shin ◽

Hee-Taik Kang

Keyword(s):

Retrospective Study ◽

Proportional Hazards ◽

Smoking Status ◽

Economic Status ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Cerebrovascular Diseases ◽

Cox Proportional Hazards ◽

Tyg Index ◽

All Cause Mortality

Background The triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance. We aimed to investigate the TyG index in relation to cardio-cerebrovascular diseases (CCVDs and mortality. Methods This retrospective study included 114,603 subjects. The TyG index was categorized into four quartiles by sex: Q1, <8.249 and <8.063; Q2, 8.249‒<8.614 and 8.063‒<8.403; Q3, 8.614‒< 8.998 and 8.403‒<8.752; and Q4, ≥8.998 and ≥8.752, in men and women, respectively. To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the primary outcomes (CCVDs and all-cause mortality) and secondary outcomes (cardiovascular diseases [CVDs], cerebrovascular diseases [CbVDs], CCVD-related deaths, or all-cause deaths), Cox proportional hazards regression models were adopted. Results Compared to Q1, the HRs (95% CIs) for the primary outcomes of Q2, Q3, and Q4 were 1.062 (0.981‒1.150), 1.110 (1.024−1.204), and 1.151 (1.058−1.252) in men and 1.099 (0.986−1.226), 1.046 (0.938−1.166), and 1.063 (0.954−1.184) in women, respectively, after adjusted for age, smoking status, drinking status, physical activity, body mass index, systolic blood pressure, low-density lipoprotein cholesterol, economic status, and anti-hypertensive medications. Fully adjusted HRs (95% CIs) for CVDs of Q2, Q3, and Q4 were 1.114 (0.969−1.282), 1.185 (1.031−1.363), and 1.232 (1.068−1.422) in men and 1.238 (1.017−1.508), 1.183 (0.971−1.440), and 1.238 (1.018−1.505) in women, respectively. The adjusted HRs (95% CIs) for ischemic CbVDs of Q2, Q3, and Q4 were 1.005 (0.850−1.187), 1.225 (1.041−1.441), and 1.232 (1.039−1.460) in men and 1.040 (0.821−1.316), 1.226 (0.981−1.532), and 1.312 (1.054−1.634) in women, respectively, while the TyG index was negatively associated with hemorrhagic CbVDs in women but not in men. The TyG index was not significantly associated with CCVD-related death or all-cause death in either sex. Conclusions Elevated TyG index was positively associated with the primary outcomes (CCVDs and all-cause mortality) in men and predicted higher risk of CVDs and ischemic CbVDs in both sexes.

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