BackgroundCardiobacterium is a fastidious Gram-negative bacillus, and is a rare human pathogen in clinical settings. Herein, we describe a case of Cardiobacterium valvarum (C. valvarum) endocarditis with a rare complication of cerebral hemorrhage after mitral valve replacement (MVR), tricuspid valve prosthesis (TVP) and vegetation removal operation.Case presentationA 41-year-old woman who had a history of gingivitis developed into infective endocarditis due to the infection of C. valvarum. Then, she was hospitalized to receive MVR, TVP and vegetation removal operation. The indicators of patient tended to be normal until the abrupt cerebral hemorrhage occurred on day 15 after operation. This is the first well-described case of C. valvarum infection in China, and the first report of C. valvarum endocarditis with cerebral hemorrhage after MVR, TVP and vegetation removal operation worldwide.ConclusionsWe reported the first case of C. valvarum infection in China clinically, with a rare complication of cerebral hemorrhage after MVR, TVP and vegetation removal operation.
<p>PDF file - 589K, Supplementary Fig. S1 Elevated MDK levels in the culture medium of HCC cell lines compared with normal liver cell lines. Supplementary Fig. S2 The prognostic values of AFP and MDK levels for HCC patients. Supplementary Fig. S3.Expression of serum MDK in another independent cohort (cohort B) from Egypt. Supplementary Fig. S4. Logistic Regression Model to combine information of MDK and AFP for prediction of HCC in the learning cohort A (n=252): Comparison of AUROC for diagnosis HCC through logist regression model I, serum MDK and AFP. Supplementary Fig. S5. Positive predictive value (PPV) and negative predictive value (NPV) for identifying HCC patients through serum MDK according to different prevalence. Supplementary Fig. S6. Correlation between serum AFP and MDK levels in HCC patients (n=252). Supplementary Fig. S7. Serum MDK is elevated in different HCC subsets, No significant difference in serum MDK levels was found between the learning cohort A and the external validation cohort of HCC patients(P=0.398), or between the early stage HCC patients in learning and validation cohort (P=0.295). Table S1. Relationship between MDK expression and clinicopathological features of HCC patients. Table S2. Clinical and biochemical characteristics of liver cirrhosis (LC) patients in cohort A. Table S3. Baseline characteristics of the hospital controls with different etiologies from learning Cohort A. Table S4. Clinical characteristics of HCC patients according to different cohorts in this study. Table S5. MDK protein levels in cancer-free cirrhotic liver and HCC tissues. Table S6. Comparison of AFP and MDK with clinicopathological parameters in learning cohort A. Table S7.Univariate Cox-regression Analyses of Factors Associated With OS and TTR. Table S8. Sensitivities and specificities of AFP and MDK according to various cutoff values. Table S9. Cross-validation of the diagnostic ability of serum MDK. Table S10. Comparison of MDK with clinicopathological parameters in validation cohort C.</p>
<div>Abstract<p><b>Purpose:</b> To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage.</p><p><b>Experimental Design:</b> MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed.</p><p><b>Results:</b> MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred.</p><p><b>Conclusions:</b> Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas. <i>Clin Cancer Res; 19(14); 3944–54. ©2013 AACR</i>.</p></div>
<div>Abstract<p><b>Purpose:</b> To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage.</p><p><b>Experimental Design:</b> MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed.</p><p><b>Results:</b> MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred.</p><p><b>Conclusions:</b> Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas. <i>Clin Cancer Res; 19(14); 3944–54. ©2013 AACR</i>.</p></div>
<p>PDF file - 589K, Supplementary Fig. S1 Elevated MDK levels in the culture medium of HCC cell lines compared with normal liver cell lines. Supplementary Fig. S2 The prognostic values of AFP and MDK levels for HCC patients. Supplementary Fig. S3.Expression of serum MDK in another independent cohort (cohort B) from Egypt. Supplementary Fig. S4. Logistic Regression Model to combine information of MDK and AFP for prediction of HCC in the learning cohort A (n=252): Comparison of AUROC for diagnosis HCC through logist regression model I, serum MDK and AFP. Supplementary Fig. S5. Positive predictive value (PPV) and negative predictive value (NPV) for identifying HCC patients through serum MDK according to different prevalence. Supplementary Fig. S6. Correlation between serum AFP and MDK levels in HCC patients (n=252). Supplementary Fig. S7. Serum MDK is elevated in different HCC subsets, No significant difference in serum MDK levels was found between the learning cohort A and the external validation cohort of HCC patients(P=0.398), or between the early stage HCC patients in learning and validation cohort (P=0.295). Table S1. Relationship between MDK expression and clinicopathological features of HCC patients. Table S2. Clinical and biochemical characteristics of liver cirrhosis (LC) patients in cohort A. Table S3. Baseline characteristics of the hospital controls with different etiologies from learning Cohort A. Table S4. Clinical characteristics of HCC patients according to different cohorts in this study. Table S5. MDK protein levels in cancer-free cirrhotic liver and HCC tissues. Table S6. Comparison of AFP and MDK with clinicopathological parameters in learning cohort A. Table S7.Univariate Cox-regression Analyses of Factors Associated With OS and TTR. Table S8. Sensitivities and specificities of AFP and MDK according to various cutoff values. Table S9. Cross-validation of the diagnostic ability of serum MDK. Table S10. Comparison of MDK with clinicopathological parameters in validation cohort C.</p>
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