Response patterns of routinely measured inflammatory and coagulatory parameters in sepsis

BackgroundSepsis is characterized by a pro-inflammatory and pro-coagulatory shift which can induce life-threatening complications. Close monitoring and risk stratification of sepsis patients is crucial for proper treatment and consequently patient outcome. Therefore, this study focuses on the response patterns of inflammatory and coagulatory parameters used in clinical routines to estimate the course of sepsis.MethodsA total of 1,110 patients diagnosed with sepsis were retrospectively analyzed to identify response patterns for risk stratification of routine parameters measured at the peak level of C-reactive protein. Cluster analysis was used and the differences in the patient characteristics and 28-day survival were assessed. Cox proportional hazards regression model for survival stratified by the clusters was performed.ResultsThe analyses revealed the parameters to have five distinct response patterns. These clusters reflect the etiology as well as the course of sepsis associated with different mortalities. Here, impairment of the liver plays a crucial role in the ability to appropriately respond to sepsis. Of the routinely measured parameters, C-reactive protein and antithrombin seem to be unspecific for stratification of septic patients. Adjusted for the individual clusters, survival was associated with an increase in fibrinogen (p = 0.0042), platelets (p = 0.0003) and PT (p = 0.001) as well as a decrease in leukocytes (p = 0.034).ConclusionsThis study reveals that patients have distinct response patterns of inflammatory and coagulatory parameters depending on disease etiology. These patterns are associated with different mortalities although the patients have similar levels of C-reactive protein. Independently of the type of response, good coagulatory capacity seems to be crucial for patient survival.

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Abstract 25: Six-year Change in C-reactive Protein Levels and Risk of Incident Diabetes, Cardiovascular Events and Mortality

Circulation ◽

10.1161/circ.129.suppl_1.25 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Christina M Parrinello ◽

Pamela L Lutsey ◽

Christie M Ballantyne ◽

Aaron R Folsom ◽

James S Pankow ◽

...

Keyword(s):

Cardiovascular Disease ◽

Proportional Hazards ◽

Cohort Analysis ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

C Reactive Protein ◽

Baseline Measure ◽

Reactive Protein ◽

Inflammatory Status ◽

Increased Risk

Background: High levels of C-reactive protein (CRP) are associated with cardiovascular disease, diabetes and mortality. It is unclear whether changes in CRP or persistently high CRP are associated with these outcomes beyond the baseline measure. Methods: We conducted a prospective cohort analysis of 10,229 participants from the ARIC Study with two measurements of CRP six years apart (at visits 2 and 4, 1990-92 and 1996-98, respectively). CRP was categorized into two groups using a standard cut-point for defining high levels (≥3 vs. <3 mg/L). Six-year change in CRP was categorized as: persistently not high (<3 mg/L), decreasing (≥3 to <3 mg/L), increasing (<3 to ≥3 mg/L), and persistently high (≥3 mg/L). Cox proportional hazards models were used to assess the association between visit 2 CRP, visit 4 CRP and six-year change in CRP and each of the following outcomes from visit 4 through 2010: diabetes, coronary heart disease, ischemic stroke, heart failure and all-cause mortality. Models were adjusted for traditional risk factors at visit 2. Sensitivity analyses additionally adjusted for visit 4 covariates. Results: Persons with CRP ≥3 mg/L at visit 2 or 4 had higher risk of each outcome compared to those with CRP <3 mg/L ( Table ). We observed higher risk of all outcomes in persons with persistently high CRP, and of all outcomes except stroke in persons with increasing CRP, compared to those with CRP <3 mg/L at both visits ( Table ). Persons whose CRP decreased from high to <3 mg/L did not have significantly increased risk of cardiovascular outcomes or diabetes compared to those with CRP persistently <3 mg/L. Results were similar after adjusting for visit 4 covariates. Conclusions: Persons with sustained high levels of CRP or whose CRP increased to high levels had higher risk of diabetes, cardiovascular disease, and death, while those whose levels decreased from high to moderate or low were at lower risk. Multiple measures of CRP may better characterize inflammatory status and provide more comprehensive information regarding long-term risk.

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Abstract 14093: High-Sensitivity C-reactive Protein Modifies the Effect of Lipoprotein (a) on Cardiovascular Risk: The Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽

10.1161/circ.142.suppl_3.14093 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Wei Zhang ◽

Jaime L Speiser ◽

Miguel Cainzos Achirica ◽

Khurram Nasir ◽

Michael Tsai ◽

...

Keyword(s):

Proportional Hazards ◽

Reference Group ◽

High Sensitivity ◽

Chinese Americans ◽

Cox Proportional Hazards ◽

Atherosclerotic Cardiovascular Disease ◽

C Reactive Protein ◽

Lipoprotein A ◽

Reactive Protein ◽

Ascvd Risk

Introduction: Lipoprotein (a) (Lp(a)) and inflammation, as represented by elevated high-sensitivity C-reactive protein (hsCRP) concentration, are both considered as risk-enhancers in the 2018 AHA/ACC Cholesterol guidelines. However, little is known as to whether the association of Lp(a) with atherosclerotic cardiovascular disease (ASCVD) risk is modified by inflammation. Objective: We assessed whether hsCRP modifies the association of Lp(a) with ASCVD risk. Methods: MESA participants with baseline hsCRP and Lp(a) levels were included. Incident ASCVD events were ascertained from baseline through 2017. Time to incident ASCVD was analyzed using Kaplan Meir curves. Cox proportional hazards models were used to assess the association between Lp(a), hsCRP, and time to ASCVD events adjusting for covariates. Results: The study included 4,654 participants with mean age of 62 and 52.5% females (1,702 Caucasians, 557 Chinese Americans, 1,336 African Americans and 1,059 Hispanics). With a mean 13.6-year follow-up, 676 ASCVD events occurred among 4,609 participants (Figure 1). In participants with hsCRP <2mg/L, the association of Lp(a) (per 1 Log unit increase) and risk for ASCVD as represented by hazard ratio (HR) and 95%CI was 1.01 (0.79, 1.28). In subjects with hsCRP ≥2mg/L, the risk increased to 1.26 (1.01, 1.58). When compared to the reference group with Lp(a) <50mg/dL and hsCRP <2mg/L, the risk for ASCVD in participants with Lp(a) ≥50mg/dL and hsCRP <2mg/L was 1.13 (0.85, 1.50) and in those with Lp(a) <50mg/dL and hsCRP ≥2mg/L was 1.09 (0.92, 1.31). The risk increased significantly to 1.62 (1.26, 2.07) in participants with Lp(a) ≥50mg/dL and hsCRP ≥2mg/L. Conclusions: Lp(a)-related ASCVD risk is modified by hsCRP levels. The findings of this analysis suggest that Lp(a) may serve as a risk enhancing factor in individuals with hsCRP level ≥2mg/L. Future studies are needed to determine whether Lp(a) is associated with risk of ASCVD in the absence of subclinical inflammation.

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Risk Evaluation of Denosumab And Zoledronic Acid For Medication-Related Osteonecrosis of The Jaw In Patients With Bone Metastases: A Propensity Score-Matched Analysis

10.21203/rs.3.rs-693498/v1 ◽

2021 ◽

Author(s):

Hiroaki Ikesue ◽

Kohei Doi ◽

Mayu Morimoto ◽

Masaki Hirabatake ◽

Nobuyuki Muroi ◽

...

Keyword(s):

Zoledronic Acid ◽

Bone Metastasis ◽

Propensity Score ◽

Proportional Hazards ◽

Significant Risk ◽

Patient Characteristics ◽

Osteonecrosis Of The Jaw ◽

Cox Proportional Hazards ◽

Close Monitoring ◽

Patients With Cancer

Abstract Purpose: This study evaluated the risk of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer who received denosumab or zoledronic acid (ZA) for treating bone metastasis.Methods: The medical records of patients were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. The primary endpoint was a comparison of the risk of developing MRONJ between the denosumab and ZA groups. Propensity score matching was used to control for baseline differences between patient characteristics and compare outcomes for both groups.Results: Among the 799 patients enrolled, 58 (7.3%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the ZA group (9.6% [39/406] vs. 4.8% [19/393], p = 0.009). Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.65–5.25; p < 0.001) and tooth extraction after starting ZA or denosumab (HR, 4.26; 95% CI, 2.38–7.44; p < 0.001) were significant risk factors for MRONJ. Propensity score-matched analysis confirmed that the risk of developing MRONJ was significantly higher in the denosumab group than in the ZA group (HR, 2.34; 95% CI, 1.17–5.01; p = 0.016). Conclusion: The results of this study suggest that denosumab poses a significant risk for developing MRONJ in patients treated for bone metastasis, and thus these patients require close monitoring.

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Biomarkers Associated with Death After Initiating Treatment for Tuberculosis and HIV in Patients with Very Low CD4 Cells

Pathogens and Immunity ◽

10.20411/pai.v3i1.235 ◽

2018 ◽

Vol 3 (1) ◽

pp. 46 ◽

Cited By ~ 1

Author(s):

Fred Richard Sattler ◽

Daniel Chelliah ◽

Xingye Wu ◽

Alejandro Sanchez ◽

Michelle A. Kendall ◽

...

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

C Reactive Protein ◽

Retrospective Case ◽

Reactive Protein ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

Treatment Naïve ◽

Low Bmi

Background: The risk of short-term death for treatment naive patients dually infected with Mycobacterium tuberculosis and HIV may be reduced by early anti-retroviral therapy. Of those dying, mechanisms responsible for fatal outcomes are unclear. We hypothesized that greater malnutrition and/or inflammation when initiating treatment are associated with an increased risk for death.Methods: We utilized a retrospective case-cohort design among participants of the ACTG A5221 study who had baseline CD4 < 50 cells/mm3. The case-cohort sample consisted of 51 randomly selected participants, whose stored plasma was tested for C-reactive protein, cytokines, chemokines, and nutritional markers. Cox proportional hazards models were used to assess the association of nutritional, inflammatory, and immunomodulatory markers for survival.Results: The case-cohort sample was similar to the 282 participants within the parent cohort with CD4 < 50 cells/mm3. In the case cohort, 7 (14%) had BMI < 16.5 (kg/m2) and 17 (33%) had BMI 16.5-18.5(kg/m2). Risk of death was increased per 1 IQR width higher of log10 transformed level of C-reactive protein (adjusted hazard ratio (aHR) = 3.42 [95% CI = 1.33-8.80],P = 0.011), interferon gamma (aHR = 2.46 [CI = 1.02-5.90], P = 0.044), MCP-3 (3.67 [CI = 1.08-12.42], P = 0.037), and with IL-15 (aHR = 2.75 [CI = 1.08-6.98], P = 0.033) and IL-17 (aHR = 3.99 [CI = -1.06-15.07], P = 0.041). BMI, albumin, hemoglobin, and leptin levels were not associated with risk of death.Conclusions: Unlike patients only infected with M. tuberculosis for whom malnutrition and low BMI increase the risk of death, this relationship was not evident in our dually infected patients. Risk of death was associated with significant increases in markers of global inflammation along with soluble biomarkers of innate and adaptive immunity.

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Low Intracellular Water, Overhydration, and Mortality in Hemodialysis Patients

Journal of Clinical Medicine ◽

10.3390/jcm9113616 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3616

Author(s):

Carolina Gracia-Iguacel ◽

Emilio González-Parra ◽

Ignacio Mahillo ◽

Alberto Ortiz

Keyword(s):

Proportional Hazards ◽

Hemodialysis Patients ◽

Cox Proportional Hazards ◽

Intracellular Water ◽

C Reactive Protein ◽

Reactive Protein ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

Over Time

Background: In hemodialysis patients, extracellular water (ECW) overload predicts all-cause and cardiovascular mortality. The primary aim of the present study was to analyze changes in post-dialysis (i.e., following removal of excess ECW) ECW, intracellular water (ICW), and the overhydration (OH) parameter over time. Additionally, the association of these parameters with mortality was explored. Patients and methods: Prospective study of prevalent hemodialysis patients (n = 124) followed for a median of 20 (interquartile range (IQR) 8–31) months. In three visits, inflammation (C-reactive protein) and post-dialysis fluid status (bioimpedance, BIS) were assessed. Results: During follow-up, the overhydration (OH) parameter increased (−0.696 ± 1.6 vs. 0.268 ± 1.7 L; p = 0.007) at the expense of a decrease in intracellular water (ICW) (19.90 ± 4.5 vs. 18.72 ± 4.1 24 L; p = 0.006) with a non-significant numerical increase in ECW/ICW ratio (0.795 ± 0.129 vs. 0.850 ± 0.143; p = 0.055). Baseline ICW positively correlated with muscle mass and energy intake and negatively with C-reactive protein and it was lower in those who died than in survivors (15.09 ± 2.36 vs. 18.87 ± 4.52 L; p = 0.004). In Kaplan–Meier analysis, patients with low baseline ICW (≤17 L) and high ECW/ICW ratio (≥0.84) were at an increased risk of death. Baseline ICW was also associated with the risk of death in adjusted Cox proportional hazards models (HR 0.62 (0.40–0.98) p = 0.04). Conclusions: In hemodialysis patients, the post-dialysis OH parameter increased over time while ICW decreased, without changes in ECW. Low baseline post-dialysis ICW correlated with muscle wasting and inflammation and was an independent risk factor for mortality.

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The Association of On-Admission Blood Hemoglobin, C-Reactive Protein, and Serum Creatinine With 2-Year Mortality of Patients With Femoral Neck Fractures

Geriatric Orthopaedic Surgery & Rehabilitation ◽

10.1177/21514593211037758 ◽

2021 ◽

Vol 12 ◽

pp. 215145932110377

Author(s):

Arkan Sayed-Noor ◽

Bariq Al-Amiry ◽

Alan Alwan ◽

Björn Knutsson ◽

Björn Barenius

Keyword(s):

Femoral Neck ◽

Serum Creatinine ◽

Proportional Hazards ◽

Healthcare Providers ◽

Cognitive Status ◽

Cox Proportional Hazards ◽

C Reactive Protein ◽

Reactive Protein ◽

Hemoglobin C ◽

Cox Proportional Hazards Models

Introduction The mortality of femoral neck fracture (FNF) is high and every effort should be made to identify and manage any possible risk factors. The aim of this study was to evaluate whether on-admission hemoglobin (Hb) level, C-reactive protein (CRP), and serum creatinine were associated with 2-year mortality after FNF. Patients and Methods In this retrospective observational cohort study, we considered for inclusion all displaced FNF patients 65 years and above treated with hemi-arthroplasty between February 2011 and May 2015. We documented the age, sex, cognitive status, and American Society of Anesthesiologists (ASA) classification. The Hb level, CRP, and serum creatinine were measured. The medical records were followed up for 2 years. We fitted different crude and adjusted Cox proportional hazards models to examine whether Hb level <100 g/L, CRP >20 mg/L, and serum creatinine >100 μmol/L were associated with the 2-year mortality, adjusted for age, sex, and ASA class. Results A total of 290 patients [208 females (72%), mean age 84 years] were included in the study. More than 50% of patients had impaired cognition and ASA class 3–4. Of the 290 patients, 38.3% ( n = 111) had died within 2 years after surgery. Mortality among males was 46.3% ( n = 38) while mortality among females was 35,1% ( n = 73), p = 0.07. We found that on-admission Hb level <100 g/L was associated with 2-year mortality (HR = 3.3, 95% CI: 1.3–8.3, p < 0.01) while CRP >20 mg/L and serum creatinine >100 μmol/L were not associated with 2-year mortality ( p = 0.89 and p = 0.31, respectively). Conclusion On-admission Hb level <100 g/L, but not CRP >20 mg/L and serum creatinine >100 μmol/L, was associated with 2-year mortality. These results can help healthcare providers identify high-risk FNF patients who probably would benefit from optimized perioperative medical management.

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Serum choline is associated with hepatocellular carcinoma survival: a prospective cohort study

10.21203/rs.2.19868/v1 ◽

2020 ◽

Author(s):

Zhao-Yan Liu ◽

Dinuerguli Yishake ◽

Ai-Ping Fang ◽

Dao-Ming Zhang ◽

Gong-Cheng Liao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

High Performance ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

C Reactive Protein ◽

Cancer Specific Survival ◽

Reactive Protein ◽

Cox Proportional Hazards Models ◽

Hazard Ratios

Abstract Background: Higher choline/betaine levels have been linked to lower risk of liver cancer, whereas existing data in relation to hepatocellular carcinoma (HCC) prognosis are scarce. Our objective was to examine the associations of the serum choline and betaine with HCC survival. Methods: 866 newly diagnosed HCC patients were enrolled in the Guangdong Liver Cancer Cohort. Serum choline and betaine were assessed using high-performance liquid chromatography with online electro-spray ionization tandem mass spectrometry. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Both LCSS (T3 vs. T1: HR=0.69, 95% CI: 0.51-0.94; P-trend <0.05) and OS (T3 vs. T1: HR=0.73, 95% CI: 0.54-0.99; P-trend <0.05) were better with sex-specific tertiles of serum choline levels. The associations were not significantly modified across strata of selected prognostic factors, except in the different C-reactive protein (CRP) levels, the favorable associations between serum choline and LCSS and OS were only existed among patients with CRP ≥3.0 mg/L. No significant associations were found between serum betaine levels and either LCSS or OS. Conclusions: This study revealed that higher serum choline levels were associated with better HCC survival, especially in HCC patients with systemic inflammation status. No significant associations were found between serum betaine and HCC survival. Our finding might open new prospect in understanding the benefits of choline on HCC survival. Registration: The Guangdong Liver Cancer Cohort was registered at clinicaltrials.gov as NCT 03297255.

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Abstract 3742: Elevated Brain Natriuretic Peptide and C-reactive Protein Interactively Increased Cardiovascular and All-cause Mortality Risk in Hemodialysis Patients

Circulation ◽

10.1161/circ.116.suppl_16.ii_851 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Kyuichi Furuhashi ◽

Hideki Ishii ◽

Hiroshi Takahashi ◽

Toru Aoyama ◽

Takanobu Toriyama ◽

...

Keyword(s):

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Mortality Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

C Reactive Protein ◽

Reactive Protein ◽

Risk Of Mortality ◽

All Cause Mortality ◽

Serum Crp

Background: It has been established that elevated brain natriuretic peptide (BNP) and C-reactive protein (CRP) levels are increasingly associated with cardiovascular (CV) morbidity. We examined the prognostic usefulness of combining BNP and CRP for predicting CV mortality in hemodialysis (HD) patients. Methods: Plasma BNP and serum CRP were measured consecutively in 500 HD patients. These patients were divided into 4 groups according to plasma BNP levels; Quartile 1 (Q1): < 45 ng/L, Q2: 145–266 ng/L, Q3: 267– 628 ng/L, and Q4: >628 ng/L, and serum CRP levels; Q1: <0.09 mg/dl, Q2: 0.09 – 0.27 mg/dl, Q3: 0.27–1.17mg/dl and Q4: >1.17mg/dl, respectively. All patients were followed up for 8 years. Results: On Cox proportional hazards analysis, hazard ratio (HR) of elevated BNP levels was 3.93 (95%CI 2.06 –7.52 for Q4 vs Q1) for CV mortality and 3.51 (95%CI 2.18 –5.64 for Q4 vs Q1) for all-cause mortality, respectively (both p<0.0001). Similarly, HR of elevated CRP levels was 6.00 (95%CI 2.89 –12.45) for CV mortality and 8.19 (95%CI 4.53–14.77) for all-cause mortality, respectively (both p<0.0001). In the setting of combination of BNP and CRP, the risk of CV mortality was 23.6-fold in the highest quartile on both BNP and CRP compared with the lowest quartile on both BNP and CRP. Similarly, the risk of mortality was 45.3-fold (Figure ). These variables were significant after adjustment for other CV risk factors. Conclusions: Elevated BNP and CRP interactively increased CV and all-cause mortality risk in HD patients. The combination of BNP and CRP is useful for risk stratification in HD patients because the combination of these variables is more closely related to outcome than either variable alone.

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Risk factors for the recurrence of relapsing polychondritis

10.21203/rs.3.rs-808558/v1 ◽

2021 ◽

Author(s):

Tsuneyasu Yoshida ◽

Hajime Yoshifuji ◽

Mirei Shirakashi ◽

Akiyoshi Nakakura ◽

Kosaku Murakami ◽

...

Keyword(s):

Risk Factors ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Relapsing Polychondritis ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

C Reactive Protein ◽

Reactive Protein ◽

Initial Recurrence ◽

Pre Treatment

Abstract Background Although the survival rates of relapsing polychondritis (RP) have increased remarkably, the high recurrence rate remains a significant concern for physicians and patients. This retrospective study aimed to investigate the risk factors for RP recurrence. Methods Patients with RP who presented to Kyoto University Hospital from January 2000 to March 2020 and fulfilled Damiani's classification criteria were included. Patients were classified into recurrence and non-recurrence groups. Risk factors for RP recurrence were analysed using a Cox proportional hazards model, and Kaplan–Meier survival curves were drawn. Results Thirty-four patients were included. Twenty-five patients (74%) experienced 64 recurrences (mean: 2.56 recurrences per patients). The median duration before the first recurrence was 202 [55 − 382] days. The median prednisolone dose at the initial recurrence was 10 [5 − 12.75] mg/day. Tracheal involvement was significantly more frequent in the recurrence group at the initial presentation (44.0% vs. 0.0%, p = 0.0172) than in the non-recurrence group, and pre-treatment C-reactive protein levels were significantly high (4.7 vs 1.15 mg/dL, p = 0.0024). The Cox proportional hazards model analysis revealed that tracheal involvement (HR 4.266 [1.535 − 13.838], p = 0.0048), pre-treatment C-reactive protein level (HR 1.166 [1.040 − 1.308], p = 0.0085), and initial prednisolone monotherapy (HR 4.443 [1.515 − 16.267], p = 0.0056) may be associated with recurrence. The median time before the initial recurrence was significantly longer in patients who received combination therapy with prednisolone and immunosuppressants or biologics (400 vs 70 days, p = 0.0015). Conclusions Tracheal involvement, pre-treatment C-reactive protein level, and initial prednisolone monotherapy were risk factors for recurrence in patients with RP. Initial combination therapy with prednisolone and immunosuppressants may delay recurrence.

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