Assessing the Prognostic Performance of the Child-Pugh, Model for End-Stage Liver Disease, and Albumin-Bilirubin Scores in Patients with Decompensated Cirrhosis: A Large Asian Cohort from Gastroenterology DepartmentRead the full article
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Upregulated Seizure-Related 6 Homolog-Like 2 Is a Prognostic Predictor of Hepatocellular Carcinoma
Seizure-related 6 homolog-like 2 (SEZ6L2), which is localized on the cell surface, has been found to be associated with tumor angiogenesis and lung cancer progression. However, the role of SEZ6L2 in hepatocellular carcinoma (HCC) is still unclear. We obtained data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to investigate SEZ6L2 expression and regulation in HCC. Then, HCC tissue samples were collected to verify SEZ6L2 by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining (IHC). Patient information was collected for survival and prognosis analysis. qRT-PCR, IHC, and bioinformatics analysis showed that the SEZ6L2 protein was highly expressed in HCC samples. Clinical data showed that high SEZ6L2 protein expression was correlated with tumor-node-metastasis (TNM) stages (), tumor number (), and tumor size (). Meanwhile, SEZ6L2 overexpression was closely associated with poor overall survival and disease-free survival in HCC patients. Moreover, SEZ6L2 is an independent prognostic predictor for the survival of HCC patients. This study suggests a significant correlation between SEZ6L2 and HCC, which means that SEZ6L2 may potentially serve as a useful prognostic biomarker for HCC patients.
Prediction of Pleural Invasion in Challenging Non-Small-Cell Lung Cancer Patients Using Serum and Imaging Markers
Introduction. Preoperative detection of pleural invasion in lung cancer patients is key to curative surgical treatment. We tried to predict pleural invasion in non-small-cell lung cancer patients with <100 ml pleural fluid. Methods. Patients admitted from August 1, 2011, to December 31, 2018, were retrospectively retrieved. Records of serum and imaging markers were analyzed. Results. Among 7004 patients who received surgery, 43 cases with <100 ml pleural fluid who had pleural invasion were included, and another 108 cases without pleural invasion were enrolled as controls. There were no differences in squamous cell carcinoma antigen (SCC) or neuron-specific enolase (NSE) values between the pleural invasion and noninvasion groups ( and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values ( and 0.01, respectively). There were significant differences in the location of original lung cancer (right mid lobe, ), maximum lung lesion diameter (), volume of pleural fluid (nondetectable vs. detectable fluid, ), pleural sign (), and positron emission tomography/computed tomography- (PET/CT-) predicted pleural invasion () between the pleural invasion and noninvasion groups. The maximum Area-Under-the-Curve in the Receiver Operating Characteristic curve analysis was achieved with the combination of CEA, CYFRA21-1, detectable pleural fluid, PET/CT prediction, pleural sign, and location of the lung lesion. Conclusions. Serum CEA and CYFRA21-1, location of original lung cancer (right mid lobe), maximum diameter, CT-detectable pleural fluid, pleural sign by CT, and PET/CT-predicted pleural invasion were good markers for the prediction of pleural invasion in non-small-cell lung cancer patients.
Diagnostic Accuracy of Holotranscobalamin, Vitamin B12, Methylmalonic Acid, and Homocysteine in Detecting B12 Deficiency in a Large, Mixed Patient Population
Four biomarkers are commonly employed to diagnose B12 deficiency: vitamin B12 (B12), holotranscobalamin (HoloTC), methylmalonic acid (MMA), and homocysteine (Hcy). 4cB12, a combined index of the B12 status, has been suggested to improve the recognition of B12 deficiency. We aimed to evaluate the four different markers for detecting B12 deficiency, as determined by 4cB12. Within a large, mixed patient population, 11,833 samples had concurrent measurements of B12, HoloTC, MMA, and Hcy. 4cB12 was calculated according to the methods described by Fedosov. Diagnostic cutoffs as well as diagnostic accuracy for the detection of B12 deficiency were assessed with receiver operating characteristic (ROC) analysis. The median age was 56 years, and women accounted for 58.8% of the samples. Overall, the area under the curve (AUC) for the detection of subclinical B12 deficiency was highest for HoloTC (0.92), followed by MMA (0.91), B12 (0.9) and Hcy (0.78). The difference between HoloTC and B12 was driven by a significantly higher AUC for HoloTC (0.93) than for B12 (0.89), MMA (0.91), and Hcy in women 50 years and older (0.79; for all). In the detection of subclinical B12 deficiency, there were no significant differences in the AUCs of HoloTC, B12, and MMA among men and women <50 years. In conclusion, in years and in men, HoloTC, MMA, or Hcy do not appear superior to B12 for the detection of B12 deficiency. For women 50 years and older, HoloTC seems to be the preferred first-line marker for the detection of subclinical B12 deficiency.
Growth Differentiation Factor 15 in Children with Chronic Kidney Disease and after Renal Transplantation
Growth differentiation factor 15 (GDF-15) is strongly associated with cardiovascular disease (CVD). The aim of our study was to evaluate plasma and urinary levels of GDF-15 after pediatric renal transplantation (Rtx) and in children with chronic kidney disease (CKD) and its associations to cardiovascular risk factors. In this cross-sectional study, GDF-15 was measured in plasma and urine from 53 children with a renal transplant and 83 children with CKD and related to cardiovascular risk factors (hypertension, obesity, and cholesterol) and kidney function. Forty healthy children served as a control group. Plasma levels of GDF-15 (median and range) for a Tx (transplantation) cohort, CKD cohort, and healthy controls were, respectively, 865 ng/L (463-3039 ng/L), 508 ng/L (183-3279 ng/L), and 390 ng/L (306-657 ng/L). The CKD and Tx cohorts both had significantly higher GDF-15 levels than the control group (). Univariate associations between GDF-15 and hyperuricemia (), elevated triglycerides (), low HDL (), and obesity () were found. However, mGFR () and hemoglobin () were the only significant predictors of GDF-15 in an adjusted analysis. Urinary GDF-15/creatinine ratios were 448 ng/mmol (74–5013 ng/mmol) and 540 ng/mmol (5–14960 ng/mmol) in the Tx cohort and CKD cohort, respectively. In the CKD cohort, it was weakly correlated to mGFR (, ). Plasma levels of GDF-15 are elevated in children with CKD and after Rtx. The levels were not associated with traditional cardiovascular risk factors but strongly associated with renal function.
Short-Term Prognosis Value of sST2 for an Unfavorable Outcome in Hypertensive Patients
Background. sST2 represents a useful biomarker for the diagnosis and prognosis of patients with heart failure, but limited data is available on its role in patients with hypertension. The aim of this study is to evaluate the short-term prognosis value of sST2 for an unfavorable outcome in hypertensive patients. Methods. This was a prospective observational study which enrolled 80 patients with hypertension, who were followed for one year. All patients underwent clinical, laboratory (including sST2), and echocardiographic assessment at baseline. The patients were grouped according to the cardiovascular (CV) events reported during the follow-up: group A (with CV events) and group B (without CV events). Results. Overall, 59 CV events were reported during the follow-up period. Compared to group B, the patients in group A had significantly higher sST2 levels, a higher number of CV risk factors, and a higher left ventricle mass. Except for the diastolic dysfunction parameters, the echocardiographic findings were similar in the two groups. Patients in group A had a lower ratio, larger deceleration time, and increased telediastolic pressure as quantified by the ratio than those in group B. Multivariate logistic regression analysis showed that sST2 and fasting plasma glucose at baseline were independent predictors for the CV events reported during the follow-up period. were associated with poor clinical outcomes (, Kaplan-Meier analysis). Conclusions. sST2 levels were correlated with the risk of adverse CV outcomes in hypertensive patients and may represent a useful prognostic marker in these patients.
Upregulated Expression of Intestinal Antimicrobial Peptide HD5 Associated with Renal Function in IgA Nephropathy
Purpose. It was reported that gut-kidney axis may play an important role in IgA nephropathy (IgAN). Previous five GWASs of different populations for IgAN have discovered several genes related to intestinal immunity, including DEFA gene. However, the roles of the encoded proteins of DEFA5/6 which were called intestinal antimicrobial peptides HD5 and HD6 were not clear in kidney disease, such as IgAN. The purpose of this study was to clarify the association of HD5 and HD6 with IgAN. Methods. We measured HD5 and HD6 in serum, urine, and kidney of IgAN patients and normal controls by ELISA, Western blot, and immunofluorescence. The association of HD5 or HD6 levels with clinical and pathologic phenotypes was analyzed. Results. Serum levels of HD5 and HD6 were significantly higher in IgAN patients than those in normal controls. Baseline serum HD5 levels were significantly associated with eGFR () and tubular atrophy/interstitial fibrosis () by stepwise multivariate regression analysis. Compared to the patients with serum HD5 below the median level, patients with elevated serum HD5 above the median level had a significantly worse renal outcome (log-rank test, ) by Kaplan-Meier analysis. A Cox regression model showed that serum HD5 was an independent prognostic factor (, ) after adjusting for the well-known predictors of outcome in IgAN patients. In renal biopsies of IgAN patients, HD5 was significantly expressed in the damaged proximal tubules, while no immunoreactive HD6 was found. Interestingly, the serum HD6 level of IgAN patients was significantly associated with gender. Conclusions. In IgAN patients, an elevated serum HD5 level at the time of renal biopsy was associated with poor renal outcomes. HD5 rather than HD6 was probably associated with renal function of IgAN patients.