Serum Fetuin-A Associated With Fatty Liver Index,Early Indicator of Nonalcoholic Fatty Liver Disease: A Strobe-Compliant Article

Increased fetuin-A has been reported in association with type 2 diabetes and other metabolic diseases. However, the large population data concerning fetuin-A and nonalcoholic fatty liver disease (NAFLD) were limited. In this study, we aimed to investigate the association of serum fetuin-A with fatty liver index (FLI), the indicator of NAFLD.A population-based cross-sectional analysis was performed in 5219 middle-aged and elderly participants who were recruited from 2 nearby urban communities in Shanghai, China. Serum fetuin-A concentrations were measured by enzyme-linked immunosorbent assay (ELISA). The fourth quartiles of FLI, alanine aminotransferance (ALT), aspartate aminotransferance (AST), and γ-glutamyl transpeptadase (GGT) were defined as elevated FLI, ALT, AST, and GGT, respectively.Fetuin-A was positively associated with log-transformed-FLI, -ALT, -AST, and -GGT after adjustment for the confounding factors (all P < 0.05). Multivariate logistic regression analysis showed that each one-standard deviation increase in serum fetuin-A (120.1 mg/L) was associated with 12% (95% confidence interval [CI] 1.01–1.25, P = 0.04), 13% (95% CI 1.06–1.21, P < 0.001), and 10% (95% CI 1.03–1.17, P = 0.005) increased risk of elevated FLI, ALT, and AST, respectively. Categorical analysis showed that as compared to the lowest quartile, the highest quartile of serum fetuin-A associated with a 35% (95% CI 0.98–1.86), 50% (95% CI 1.24–1.83), and 33% (95% CI 1.10–1.60) increased risk of elevated FLI, ALT, and AST, respectively. No significant association was found with GGT.In Chinese adults, serum fetuin-A concentrations were significantly associated with elevated FLI, ALT, and AST, the early indicators of NAFLD.     

Serum Hepcidin Levels in Childhood-Onset Ischemic Stroke: A Case-Control Study

Recently, hepcidin, an antimicrobial-like peptide hormone, has evolved as the master regulator of iron homeostasis. Despite the growing evidence of iron imbalance in childhood-onset ischemic stroke, serum hepcidin level in those patients has not yet been researched.In this study, we aimed to estimate serum (hepcidin) level in acute ischemic stroke (AIS) patients and to investigate whether subcutaneous enoxaparin sodium, which is a low-molecular-weight heparin (LMWH) derivative, could modulate serum hepcidin level in those patients.This was a case–control study included 60 (AIS) cases, and 100 healthy children with comparable age and gender as control group. For all subjects’ serum hepcidin, interleukin-6 (IL-6), and soluble transferrin receptor [sTfR]) levels were assessed by (enzyme-linked immunosorbent assay [ELISA] method). Iron parameters including (serum iron, ferritin, transferrin, and total iron binding capacity [TIBC]) were also measured. The patients were subdivided according to treatment with an LMWH derivative into 2 groups and serum hepcidin levels were assessed initially and 1 week after stroke onset for all cases.We found that AIS cases had higher serum iron, ferritin, and IL6 levels compared to the control group (all P < 0.01). Serum hepcidin was significantly higher in AIS cases (median, 36[15–73]ng/mL) compared to the control group (median, 24[10–41]ng/mL; P < 0.01). On the 1st day of AIS diagnosis, serum hepcidin levels were similar in both stroke subgroups (P > 0.05). However, on the 7th day of diagnosis serum hepcidin level decreased significantly in AIS cases treated with LMWH (group 1) (median, 36 vs 21 ng/mL; P < 0.01, respectively). Meanwhile, no significant change was observed in serum hepcidin level in AIS cases not treated with LMWH (group 2) (P > 0.05). Serum hepcidin showed significant positive correlations with serum iron, transferrin saturation, ferritin, and IL6 (r = 0.375, P < 0.05; r = 0.453, P < 0.05; r = 0.687, P < 0.01; r = 0.515, P < 0.01; respectively).Our data brought a novel observation of elevated serum hepcidin level in pediatric AIS patients and pointed out that treatment with LMWH could modulate hepcidin level in those patients.     

Association of Sodium Excretion With Metabolic Syndrome,Insulin Resistance,and Body Fat

Sodium intake was reported to be related to metabolic syndrome (MS). Although a strong association between sodium intake and blood pressure (BP) has been reported, the relationship between sodium intake and other components of MS is unknown.An observational study of 18,146 adults in the Korea National Health and Nutrition Examination Survey IV-V databases (2008–2011) was performed. Estimates of 24-h sodium excretion were made from a single fasting urine sample.A significant positive association was found between sodium excretion and systolic BP and between sodium excretion and diastolic BP in participants with and without hypertension after adjusting for multiple covariates (P < 0.001 for trend). The relationship between triglyceride or glucose levels and sodium excretion was linear (P < 0.005). In both men and women, a positive relationship between sodium excretion and waist circumference and an inverse relationship between sodium excretion and high-density lipoprotein were found (P ≤ 0.001). Body fat percentage, body fat mass, and insulin level were positively related to sodium excretion (P ≤ 0.001), and HOMA-IR was significantly associated with sodium excretion (P < 0.05). The risk of MS was elevated 1.279-fold in the second quartile of sodium excretion (95% CI, 1.088–1.504, P = 0.003), 1.479-fold in the third quartile (95% CI, 1.262–1.734; P < 0.001), and 1.929-fold in the highest quartile (95% CI 1.654–2.249, P < 0.001) compared with the lowest quartile.Sodium intake is significantly associated with all components of MS, body fat, and insulin resistance. Therefore, a high-salt diet is a significant risk factor for MS.     

Upregulated Expression of A20 on Monocytes is Associated With Increased Severity of Acute-on-Chronic Hepatitis B Liver Failure: A Case-Control Study

A20 expression is increased in various inflammatory diseases. However, the role of A20 in acute-on-chronic liver failure is unknown. This study was to evaluate A20 expression on monocytes and its associations with the severity of acute-on-chronic hepatitis B liver failure (ACHBLF).Thirty-seven patients with ACHBLF, 20 patients with chronic hepatitis B (CHB), and 15 healthy controls (HC) were enrolled in this case-control study. A20-positive monocytes were identified using flow cytometry. Serum levels of interleukin (IL)-10, IL-12p70, and TNF-α were determined using bead cytometry. A20 and IL-10 expressions were examined in THP-1 cells stimulated by lipopolysaccharide (LPS).The frequency of A20⁺ monocytes was significantly increased in patients with ACHBLF compared with HC (median [interquartile range, IQR]: 15.7 [22.8]% vs 2.5 [4.7]%, P < 0.001). Increased monocyte A20 expression was detected during the progression phase (including the mild/moderate and severe grades of ACHBLF) compared with patients in the recovery phase (both P < 0.05), and in the ACHBLF worsening group compared with patients in the improvement group (P < 0.001). LPS treatment upregulated A20 and IL-10 expressions in THP-1 cells. A20 expression on monocytes from patients with ACHBLF was positively correlated with total bilirubin (r = 0.60, P = 0.0001), direct bilirubin (r = 0.63, P < 0.0001), and MELD score (r = 0.43, P = 0.008), and inversely with prothrombin activity (r = −0.33, P = 0.046). IL-10 and TLR4 expression levels in monocytes, and serum levels of IL-10, IL-12p70, and TNF-α were increased in patients with ACHBLF compared with patients with CHB and HC.Increased A20 expression on monocytes was associated with the severity of ACHBLF.     

Elevated Serum PCT in Septic Shock With Endotoxemia Is Associated With a Higher Mortality Rate

To examine the effect of endotoxemia on the procalcitonin (PCT) serum levels and mortality rates of adult patients with septic shock diagnosed on the day of admission to the intensive care unit (ICU).A retrospective observational study was performed over a 2-year period. Levels of PCT were compared for septic shock patients with and without endotoxemia on admission to the ICU. Endotoxemia was identified with an Endotoxin Activity Assay.One hundred fifty-seven patients with septic shock were enrolled into the study. Group 1 consisted of patients with elevated endotoxin activity (EA) (n = 95, EA = 0.57 endotoxin activity unit [EAU] [0.46–0.67]) and Group 2 consisted of patients with low EA (n = 62, EA = 0.27 EAU [0.17–0.36]). Acute Physiology And Chronic Health Evaluation II (APACHE II) score and SOFA score were similar in both groups (APACHE II = 23 [16–29] and 19 [16–25]; Sequential Organ Failure Assessment [SOFA] = 10 [7–13] and 11 [8–12] in Groups 1 and 2, respectively) (nonsignificant). The PCT level was 6 times higher in Group 1 than in Group 2 (19.6 ng/mL vs. 3.1 ng/mL, P < 0.001). There was a strong correlation between EA and serum PCT (P < 0.001, R = 0.5). The presence of endotoxemia on admission to the ICU was associated with an increased mortality rate: 52% in the group of patients with endotoxemia and 25% in the group without endotoxemia. EA in survivors was 0.39 EAU (0.26–0.57) and 0.53 EAU (0.4–0.61) in nonsurvivors (P = 0.004). The median PCT level in survivors was 6.7 ng/mL (2.3–28.0), compared with 16.7 ng/mL (5.3–31.0) in nonsurvivors (P = 0.04).This observational study revealed that endotoxemia in patients with septic shock on admission to the ICU was frequently found and was associated with an elevated PCT level and a high mortality rate. Endotoxemia was a common occurrence in patients with septic shock, regardless of the infecting microorganism.     

Plasma Aldosterone Concentration Is Positively Associated With Pulse Pressure in Patients With Primary Hypertension

Increasing evidence showed a link between arterial elasticity and stiffness and pulse pressure (PP), in which plasma aldosterone may play a role. The observational study aimed to explore the potential relations between plasma aldosterone concentration (PAC) and PP in patients with hypertension.We evaluated the relation between PP and PAC in supine, seated, and upright positions in 195 patients with primary hypertension who underwent postural stimulation test. They were divided into 3 groups by tertiles of PP: PP ≤ 44 mm Hg (n = 70), 44 mm Hg < PP ≤ 51 mm Hg (n = 63), and PP ≥ 51 mm Hg (n = 62). The PAC in different postures was compared, respectively.The results showed the following. First, segregated by tertiles of PP, serum K⁺, 24-hour systolic blood pressure, 24-hour diastolic blood pressure, sex, upright PAC, and seated PAC showed statistically significant differences in groups. Second, the PAC were significantly different in 3 levels of PP regardless of postures, the individuals with PP ≥ 51 mm Hg had the highest PAC. On contrast, the patients with PAC > 12 ng/dL showed greater PP than those with PAC ≤ 12 ng/dL. Third, weak associations between PP and upright (r = 0.288, P < 0.001), seated (r = 0.265, P < 0.001), and supine postures (r = 0.191, P = 0.008) were detected by simple correlation analysis. After corrected serum K⁺, age, and sex, the partial correlation coefficients did not change greatly. Fourth, the logistic regression model was constructed with PP ≥ 40 mm Hg or PP < 40 mm Hg as the dependent variable; the serum K⁺[OR = 0.043, 95% CI: 1.09(1.00–1.12)] and PAC [OR = 0.025, 95%CI: 0.35(0.13–0.88)] were included as significant contributing factors.The results showed that higher PAC was weakly, but significantly, correlated to greater PP regardless of different postures, suggesting that higher PAC may be a risk factor of reduced arterial elasticity in patients with hypertension.     

Serum Gamma-Glutamyltransferase Levels Predict Mortality in Patients With Peritoneal Dialysis

Serum gamma-glutamyltransferase (GGT) level has been considered marker of oxidative stress as well as liver function. Serum GGT level has been reported to be associated with the mortality in hemodialysis patients. However, it is not well established whether serum GGT level is associated with all-cause mortality in peritoneal dialysis (PD) patients. The aim of this study was to determine the association between serum GGT levels and all-cause mortality in PD patients.PD patients were included from the Clinical Research Center registry for end-stage renal disease cohort, a multicenter prospective observational cohort study in Korea. Patients were categorized into 3 groups by tertile of serum GGT levels as follows: tertile 1, GGT < 16 IU/L; tertile 2, GGT = 16 to 27 IU/L; and tertile 3, GGT > 27 IU/L. Primary outcome was all-cause mortality.A total of 820 PD patients were included. The median follow-up period was 34 months. Kaplan–Meier analysis showed that the all-cause mortality rate was significantly different according to tertiles of GGT (P = 0.001, log-rank). The multivariate Cox regression analysis showed that higher tertiles significantly associated with higher risk for all-cause mortality (tertile 2: hazard ratio [HR] 2.08, 95% confidence interval [CI], 1.17–3.72, P = 0.013; tertile 3: HR 1.83, 95% CI, 1.04–3.22, P = 0.035) in using tertile 1 as the reference group after adjusting for clinical variables.Our study demonstrated that high serum GGT levels were an independent risk factor for all-cause mortality in PD patients. Our findings suggest that serum GGT levels might be a useful biomarker to predict all-cause mortality in PD patients.     

Salviae miltiorrhizae and ligustrazine hydrochloride injection combined with mecobalamin for treating diabetic peripheral neuropathy: A protocol for systematic review and meta-analysis

Objective:Currently, it is unclear whether the salviae miltiorrhizae (Danshen Salvia) and ligustrazine hydrochloride (Chuanxiong Chuanxiong) (SMLH) injection combined with mecobalamin can improve diabetic peripheral neuropathy (DPN). We conducted a systematic analysis to evaluate the clinical effects of SMLH injection combined with mecobalamin for treating DPN.Methods:Seven databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wang Fang), Chinese Biomedical Literature Database (CBM), and VIP Database for Chinese Technical Periodicals (VIP) were searched for systematic literature retrieval. Each database was searched up to 2020 to identify randomized controlled trials on DPN treated with SMLH injection combined with mecobalamin. We used the RevMan 5.3 and Stata 14.0 software to assess the risk of bias in the included trials.Results:A total of 15 publications, including 1349 samples, were reviewed. The total effective rate of SMLH injection combined with mecobalamin was 31% higher than that of mecobalamin alone (95% confidence interval [CI] = 1.23–1.38; P < .00001). The experimental group showed a significant increase in the motor conduction velocity (MCV) of the peroneal nerve (weighted mean difference [WMD] = 4.81, 95% CI 3.53–6.09; P < .00001). In addition, SMLH injection combined with mecobalamin showed a statistical significant effect on the sensory conduction velocity (SCV) of the peroneal nerve (WMD = 5.03, 95% CI = 4.16–5.90; P < .00001), and MCV of the median nerve (WMD = 5.38, 95% CI = 4.05–6.72; P < .00001). The WMD for the change in SCV in the median nerve was 4.89 m/s (95% CI = 3.88–5.89; P < .00001). The P-values of the Egger and Begg tests were 0.967 and 0.961, respectively, indicating no publication bias. Subgroup and sensitivity analyses indicated that the results for MCV and SCV of the peroneal nerve and the median nerve were stable.Conclusion:SMLH injection combined with mecobalamin can improve DPN, compared with mecobalamin alone.     

Value of Neutrophil Counts in Predicting Surgery-Related Acute Kidney Injury and the Interaction of These Counts With Diabetes in Chronic Kidney Disease Patients With Hypertension: A Cohort Study

As a component of routine blood cell analyses, the quantity of neutrophils present is a proven predictor of morbidity and mortality in several clinical settings. However, whether episodes of acute kidney injury (AKI) are associated with higher neutrophil counts in vulnerable groups, such as chronic kidney disease (CKD) patients with hypertension, are unknown. This study was conducted to investigate the relationship between neutrophil counts and the incidence of surgery-related AKI in CKD patients with hypertension.This was a retrospective cohort study of the relationship between neutrophils and surgery-related AKI. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression models.In total, 119 (11.9%) of 998 patients experienced surgery-related AKI during hospitalization from October 2008 to February 2013. We divided patients into 4 quartiles according to their neutrophil counts. After adjusting for multiple covariates, the patients in the 4th quartile of neutrophil counts had greater ORs for AKI compared to those in the 1st quartile. The incidence of AKI increased 1.59-fold for those patients with neutrophil counts ≥6.30 × 10⁹/L. There was a positive linear association between the neutrophil count upon admission and the predicted probability of AKI. The cross-validation revealed a statistically significant predictive accuracy for AKI (area under the curve (AUC) = 0.68, 95% CI, 0.67–0.69). The interaction analyses revealed that higher neutrophil counts are associated with a heightened risk of AKI in the presence of diabetes (OR = 3.38, 95% CI, 1.06–10.80). There were no interactions between neutrophil counts and age (P = 0.371), sex (P = 0.335), estimated glomerular filtration rate (P = 0.487), systolic blood pressure (P = 0.950), diastolic blood pressure (P = 0.977), the presence of chronic heart failure (P = 0.226), or sepsis (P = 0.796).The neutrophil count upon admission, an index that is easily and rapidly measured, is valuable for the prediction of surgery-related AKI in CKD patients with hypertension, especially in those with diabetes.     

Clinical significance of serum human epididymis protein 4 in liver fibrosis: An experimental study

Background:Human epididymis protein 4 (HE4) has been identified as marker for renal fibrosis. Present study aimed to investigate the clinical significance of serum HE4 in liver fibrosis.Methods:Serum from 65 liver fibrosis patients, 68 hepatic patients without fibrosis, and 50 controls was collected respectively. Serum HE4 levels were measured by chemiluminescence immunoassay and compared among the groups. The relationships between serum HE4 levels and the clinical characteristics of liver fibrosis were also analyzed. A receiver operator characteristic curve was plotted to investigate the diagnostic efficacy of serum HE4 for liver fibrosis. Child–Pugh (C–P) score and liver fibrosis score were also evaluated. Data were analyzed by statistical software 13.0.Results:Serum HE4 levels were significantly higher in liver fibrosis than that of controls [105.35 (82.64, 164.18) vs 46.2 (39.9, 58.9) pmol L⁻¹, P = .00] and hepatic patients without liver fibrosis [105.35 (82.64, 164.18) vs 51.00 (44.02, 65.65) pmol L⁻¹, P < .01]; Serum HE4 levels in liver fibrosis patients with C–P class C were significantly higher than those with C–P class A [143.75 (106.50, 186.08) vs 81.42 (69.73, 99.26) pmol L⁻¹, P = .005] and C–P class B [143.75 (106.50, 186.08) vs 113.10 (88.92, 169.50) pmol L⁻¹, P = .01]; the diagnostic sensitivity and specificity of serum HE4 levels for liver fibrosis detection were 87.5% and 81.1%, at a cutoff value of 69 pmol L⁻¹; Serum HE4 levels in alcoholic liver fibrosis were higher than that of liver fibrosis with hepatitis B virus infection [131.30 (100.67, 228.35) vs 89.46 (73.74, 116.45) pmol L⁻¹, P < .01].Conclusion:Serum HE4 was closely correlated with C–P class and might be a potential marker for liver fibrosis.     

A Meta-analysis Reveals S-1-based Chemotherapy Improves the Survival of Patients With Advanced Gastric Cancer

The aim of this study was to compare the efficacy and safety of S-1-based therapy versus non-S-1-based therapy in advanced gastric cancer (AGC) patients.Eligible studies stratifying objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in AGC patients were identified from Embase, Pubmed, Cochrane Library, and China National Knowledge Infrastructure databases. The STATA package (version 11.0) was used to pool the data from the eligible studies.Fifteen studies with 2973 AGC cases, of which 1497 (50.4%) received S-1-based therapy and 1476 (49.6%) received non-S-1-based therapy, were identified in the meta-analysis. AGC patients who had received S-1-based therapy had a higher median OS, median PFS, and ORR than those who had received 5-fluorouracil (FU)-based therapy (OS: hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80–0.98, P = 0.015; PFS: HR 0.88, 95% CI 0.80–0.98, P = 0.016; ORR: OR 1.25, 95% CI 1.08–1.45, P = 0.003, respectively). S-1-based therapy had similar efficacy to capecitabine-based therapy in terms of median OS (HR 1.14, 95% CI 0.91–1.41, P = 0.253), median PFS (HR 1.01, 95% CI 0.82–1.25, P = 0.927), and ORR (OR 0.84, 95% CI 0.63–1.12, P = 0.226). Subgroup analysis for grade 3 to 4 toxicity showed higher incidence of neutropenia (relative risk [RR] = 0.827, P = 0.006), nausea (RR = 0.808, P = 0.040), and lower diarrhea (RR = 1.716, P = 0.012) in 5-FU-based arm, and higher diarrhea (RR = 0.386, P = 0.007) in capecitabine-based arm.S-1-based chemotherapy is favorable to AGC patients with better clinical benefit than 5-FU-based chemotherapy and with equivalent antitumor compare with capecitabine-based therapy.     

Independent Association of Circulating Level of Chemerin With Functional and Early Morphological Vascular Changes in Newly Diagnosed Type 2 Diabetic Patients

There is growing evidence that chemerin, a novel adipokine elevated in obesity and metabolic syndromes, plays a crucial role in advanced atherosclerosis. This study aimed to determine the chemerin levels in diabetes and evaluate the effects of increased chemerin on early atherosclerosis.A total of 245 newly diagnosed diabetic patients and 148 age-matched, healthy, normal glucose tolerant (NGT) controls were enrolled. Anthropometric measurements and plasma parameters were examined, including body mass index (BMI), waist circumference, blood pressure, glucose, lipid profiles, inflammation markers, adipokines, and cell adhesion molecules. Vascular healthy was measured with brachial flow-mediated dilatation (FMD) and carotid intima-media thickness (IMT).Compared with NGT controls, plasma chemerin levels were higher in diabetic patients (P < 0.01) and higher chemerin level was an independent risk factor of occurrence of diabetes even after metabolic profiles were adjusted (odds ratio [OR] = 1.352, 95% CI: 1.181–1.543, P < 0.01). In patients with type 2 diabetes, chemerin was positively associated with intercellular adhesion molecule-1 (ICAM-1), E-selectin, but not vascular adhesion molecule-1 (VCAM-1) and P-selectin. We also explored that plasma chemerin level was negatively associated with brachial FMD and positively with carotid IMT. Chemerin also retained a strong association with ICAM-1, FMD, and IMT even after adjusted for age, sex, and other risk factors (ICAM-1: r = 0.150, P = 0.024; FMD: r = −0.126, P = 0.001; IMT: r = 0.325, P < 0.001). By multiple linear regression analysis, plasma chemerin levels were related to ICAM-1 even after adjustments for conventional cardiovascular risk factors (β = 0.192, P = 0.017). Moreover, logistic regression analysis showed that high chemerin level was an independent predictive variable for impaired endothelial function (OR = 1.066, 95% CI: 1.012–1.142, P = 0.048) and enhanced carotid vessel thickness (OR = 1.068, 95% CI: 1.021–1.148, P = 0.035) in diabetic patients.In summary, chemerin levels are independently associated with endothelial activation and early atherosclerosis in newly diagnosed type 2 diabetes.     

The Efficacy of Combining EGFR Monoclonal Antibody With Chemotherapy for Patients With Advanced Nonsmall Cell Lung Cancer: A Meta-Analysis From 9 Randomized Controlled Trials

Although epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) have been proved synergistic effect when combined with cytotoxic agents for advanced nonsmall cell lung cancer (NSCLC), the results of relevant clinical trials remain controversial. The purpose of this meta-analysis was to assess the advantage and toxicity profile of chemotherapy plus EGFR-mAbs versus chemotherapy alone for patients with NSCLC.We rigorously searched electronic databases for eligible studies reporting EGFR-mAbs combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC. The primary outcome was overall survival (OS). Pooled results were calculated using proper statistical methods.Nine phase II/III randomized controlled trials involved a total of 4949 participants were included. In general, compared with chemotherapy alone, the addition of EGFR-mAbs significantly improved OS (hazard ratio [HR] = 0.91, 95% confidence interval [CI]: 0.86–0.97, P = 0.006), progression-free survival (HR = 0.83, 95% CI: 0.87–0.98, P = 0.01), response rate (odd ratio [OR] = 1.28, 95% CI: 1.12–1.47, P = 0.0003), and disease control rate (OR = 1.17, 95% CI: 1.01–1.36, P = 0.04). Subgroup analysis showed that apparent OS benefit present in patients with squamous NSCLC (HR = 0.83, 95% CI: 0.74–0.93, P = 0.001), and those treatment-naive population (HR = 0.88, 95% CI: 0.82–0.95, P = 0.0006). Several manageable adverse events were markedly increased by EGFR-mAbs, such as acne-like rash, infusion reactions, and diarrhea. The risk for some ≥Grade 3 toxicities, such as leukopenia, febrile neutropenia, and thromboembolic events were slightly increased by the addition of EGFR-mAbs. In general, the toxicities of the combination strategy were tolerable and manageable.The addition of EGFR-mAbs to chemotherapy provided superior clinical benefit along with acceptable toxicities to patients with advanced NSCLC, especially those harboring squamous cancer and treatment-naive. Further validation in front-line investigation, proper selection of the potential benefit population by tumor histology, and development of prognostic biomarkers are warranted for future research and clinical application of EGFR-mAbs.     

Association of sleep disturbance with calcitonin,disease severity and health index among patients with ankylosing spondylitis

To investigate the association of sleep disturbance with calcium regulatory hormones, disease severity and health index among the patients with ankylosing spondylitis (AS).There were 104 AS patients enrolled in the cross-sectional study, and their sleep quality was recorded. Serum levels of calcium, parathyroid hormone, vitamin D3 and calcitonin were measured. We evaluated patient''s disease activity, functional ability, patient''s global assessment, physical mobility, radiographic damage and health index. Blood ESR and CRP levels were tested.Sleep quality was positively correlated with serum calcitonin levels (r = 0.260, P = .008). Bad sleep and advanced radiographic damage were found among the AS patients with detectable serum calcitonin levels (P < .05). Sleep quality was significantly correlated with disease duration, CRP, BASDAI, ASDAS-ESR, ASDAS-CRP, BASFI, BAS-G, BASMI and ASAS-HI among the AS patients (all P < .05). Female gender, longer disease duration, higher ASDAS-CRP and serum calcitonin levels (OR [95% CI] = 3.210 [1.012–10.181], P = .048) were independent factors associated with bad sleep. Inflammation, disease activity, functional ability, patient''s global assessment and cervical rotation were useful in predicting bad sleep among the AS patients, and ASDAS-CRP was the best predictor (AUC = 0.772, P < .001).Serum calcitonin levels was elevated in the AS patients with bad sleep, and may participate in the pathophysiology of sleep disturbance. Bad sleep was associated with female gender, longer disease duration, higher inflammation, disease activity, functional impairment, mobility restriction, poor patient''s global assessment and health index in AS. ASDAS-CRP was best in predicting bad sleep.     

Copeptin levels predict left ventricular systolic function in STEMI patients: A 2D speckle tracking echocardiography-based prospective observational study

In the present study, we aimed to investigate whether copeptin values on admission are related to left ventricle (LV) systolic function and its improvement at 6 months in ST-segment elevation myocardial infarction (STEMI) patients.In this single-center, prospective observational study, we included 122 STEMI patients from January 2016 to November 2016. LV systolic functions in the form of global longitudinal strain (GLS) in addition to conventional echocardiography parameters were evaluated on admission and at 6-month. Serum copeptin levels were determined using an ultrasensitive immunofluorescence assay.The study population was divided into 2 groups according to median values of copeptin. GLS was significantly lower in patients with high copeptin levels compared to those with low copeptin levels at early stage and 6-month (−16% (16–16.5) vs −15% (15–15.5), P < .001 and −18% (18–19) vs −16% (16–16.25), P < .001, respectively). Copeptin values were negatively correlated with an early and 6-month GLS (r = –0.459 at early stage and r = –0.662 at 6-month). In addition, we observed that copeptin values were negatively correlated with the improvement of GLS at 6-month follow-up (r = −0.458, P < .001 and r = −0.357, P = .005, respectively).Serum copeptin levels in STEMI patients at the time of admission may predict early and 6-month LV systolic function assessed by two-dimensional GLS. To the best of our knowledge, this study is the first to specifically address the relationship between copeptin values and GLS in STEMI patients.     

Factors Affecting Compliance With Colorectal Cancer Screening Among Households Residing in the Largely Haitian Community of Little Haiti,Miami-Dade County,Florida: An Observational Study

The United States Black population is disproportionately affected by colorectal cancer (CRC) in terms of incidence and mortality. Studies suggest that screening rates are lower among Blacks compared with non-Hispanic Whites (NHWs). However, studies on CRC screening within Black subgroups are lacking. This study examined disparities in blood stool test (BST) compliance and colonoscopy use by race/ethnicity (Haitian, NHW, non-Hispanic Black [NHB], and Hispanic) among randomly selected households in Little Haiti, Miami-Dade County, Florida.This study used cross-sectional, health and wellness data from a random-sample, population-based survey conducted within 951 households in Little Haiti between November 2011 and December 2012. BST compliance and colonoscopy use were self-reported and defined, conservatively, as the use of BST within the past 2 years and the ever use of colonoscopy by any household member. Factors associated with BST compliance and colonoscopy use were identified using logistic regression models. Analyses were restricted to households containing at least 1 member ≥50 years (n = 666).Nearly half of the households were compliant with BST (rate [95% confidence interval (CI)] = 45% [41%–49%]) and completed colonoscopy (rate [95% CI] = 53% [49%–58%]). Compliance with BST was not associated with race/ethnicity (P = 0.76). Factors independently associated with BST compliance included low educational attainment (adjusted odds ratio [AOR] = 0.63, P = 0.03), being single (AOR = 0.47, P = 0.004), retirement (AOR = 1.96, P = 0.01), and the presence of diagnosed health problems (AOR = 1.24, P = 0.01). Colonoscopy use was lower among Haitian households (46%) compared with NHW (63%), NHB (62%), and Hispanic households (54%) (P = 0.002). Factors independently associated with colonoscopy use included identifying as NHB (compared with Haitian) (AOR = 1.80, P = 0.05), being single (AOR = 0.44, P = 0.001), retirement (AOR = 1.86, P = 0.02), lack of continuous insurance (AOR = 0.45, P < 0.001), and the presence of diagnosed health problems (AOR = 1.44, P < 0.001) and physical limitations/disabilities (AOR = 1.88, P = 0.05).Compliance with BST and use of colonoscopy are low within households in the Little Haiti community. Significant disparities in the use of colonoscopy exist between Haitian and NHB households. Barriers and facilitators of colonoscopy within each racial/ethnic group need to be identified as the next step to developing culturally appropriate, community-based interventions aimed at increasing colonoscopy use in this large minority population.     

A Prospective Follow-Up of Adipocytokines in Cohort Patients With Gout: Association With Metabolic Syndrome But Not With Clinical Inflammatory Findings: Strobe-Compliant Article

The aim of this study was to determine the levels of leptin (Lep) and adiponectin (AdipoQ) in patients with gout and its relationship with joint inflammatory data and/or with metabolic syndrome (MetS) variables, during 1 year follow-up.Forty-one patients (40 males) with gout diagnosis, attending for the first time to a rheumatology department, were included. Evaluations were performed baseline, at 6 and 12 months. Variables included the following: demographic, clinical and laboratory data related to gout and associated diseases. Lep and AdipoQ determinations by the ELISA method were performed in frozen serum from each visit. The pharmacological and no-pharmacological treatment for gout and associated diseases was individualized for each patient according to published guidelines. Statistical analysis included Mann–Whitney U test, Fisher test, x², ANOVA, Cochran Q, Pearson and Spearman correlation tests, as well as linear regression.In the baseline evaluation, 29.2% had MetS (hypertriglyceridemia 66%, hypertension 44% and obesity 37%); patients with MetS had higher C reactive protein (CRP) levels [34.1 ± 28.6 vs. 12.2 ± 11.2 mg/dL, P = 0.033]. Although not significant, also had higher Lep and lower AdipoQ levels (3.2 ± 3.0 vs. 1.9 ± 1.2 ng/mL, P = 0.142 and 40.5 ± 26.8 vs. 38.0 ± 24.9 ng/mL, P = 0.877, respectively). During follow-up, our patients had significant improvement in serum uric acid (sUA) levels and variables evaluating pain and joint swelling (P ≤ 0.05). Metabolic abnormalities tended to persist or even worsen during the monitoring period: significant increase in total cholesterol (P = 0.004), tendency to higher triglycerides (P = 0.883) and slight improvement in glycaemia (P = 0.052). Lep values increased significantly during follow-up (P = 0.001) while AdipoQ levels diminished slightly (P = 0.317). Neither Lep nor AdipoQ values showed important correlation (r > 0.5) with metabolic variables or joint swelling.This study suggests that in patients with gout, concentrations of Lep and AdipoQ are more in line with the metabolic state than with clinical disease activity.     

Factors Associated With Protein-energy Malnutrition in Chronic Liver Disease: Analysis Using Indirect Calorimetry

We aimed to elucidate the incidence of protein–energy malnutrition (PEM) in patients with chronic liver disease and to identify factors linked to the presence of PEM.A total of 432 patients with chronic liver disease were analyzed in the current analysis. We defined patients with serum albumin level of ≤3.5 g/dL and nonprotein respiratory quotient (npRQ) value using indirect calorimetry less than 0.85 as those with PEM. We compared between patients with PEM and those without PEM in baseline characteristics and examined factors linked to the presence of PEM using univariate and multivariate analyses.There are 216 patients with chronic hepatitis, 123 with Child–Pugh A, 80 with Child–Pugh B, and 13 with Child–Pugh C. Six patients (2.8%) had PEM in patients with chronic hepatitis, 17 (13.8%) in patients with Child–Pugh A, 42 (52.5%) in patients with Child–Pugh B, and 10 (76.9%) in patients with Child–Pugh C (P < 0.001). Multivariate analysis revealed that Child–Pugh classification (P < 0.001), age ≥64 years (P = 0.0428), aspartate aminotransferase (AST) ≥40 IU/L (P = 0.0023), and branched-chain amino acid to tyrosine ratio (BTR) ≤5.2 (P = 0.0328) were independent predictors linked to the presence of PEM. On the basis of numbers of above risk factors (age, AST, and BTR), the proportions of patients with PEM were well stratified especially in patients with early chronic hepatitis or Child–Pugh A (n = 339, P < 0.0001), while the proportions of patients with PEM tended to be well stratified in patients with Child–Pugh B or C (n = 93, P = 0.0673).Age, AST, and BTR can be useful markers for identifying PEM especially in patients with early stage of chronic liver disease.     

Clinical and Genetic Factors Associated With Thiazide-Induced Hyponatremia

Thiazide diuretics are associated with an increased risk of hyponatremia. The aim of this study was to investigate possible predictors of thiazide-induced hyponatremia.A total of 48 patients admitted to the ward or to the emergency department due to severe thiazide-induced hyponatremia (Na < 125 mmol/L) were enrolled in our study as the case group. Another 211 hypertensive patients with normal sodium levels after treatment with thiazide diuretics were selected as the control group. Twelve tag single nucleotide polymorphism markers were selected from the Potassium Channel, Inwardly Rectifying Subfamily J, Member 1 (KCNJ1) gene: rs1231254, rs2238009, rs1148058, rs675482, rs673614, rs12795437, rs2855800, rs2509585, rs3016774, rs881333, rs4529890, and rs7116606. Clinical and genetic parameters between patients with thiazide-induced hyponatremia and the control group were compared. Logistic regression was used to analyze data.The patients with thiazide-induced hyponatremia were older (P < 0.001), predominantly female (P = 0.008), had a lower mean body mass index (BMI) (P < 0.001), and more commonly used angiotensin II receptor antagonist (P < 0.001) and spironolactone (P = 0.007) compared with the control groups. Analysis with multivariate logistic regression revealed that age (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.08–1.19, P < 0.001), female gender (OR, 4.49; 95% CI, 1.54–13.11, P = 0.006), BMI (OR, 0.80; 95% CI, 0.69–0.93, P = 0.003), and KCNJ1 rs2509585 C/T or T/T polymorphisms (OR, 5.75; 95% CI, 1.25–26.45, P = 0.03) were independent predictors for thiazide-induced hyponatremia.Older female patients with lower BMIs and KCNJ1 rs2509585 C/T or T/T polymorphisms were more likely to develop thiazide-induced hyponatremia.     

Bisphosphonates in the Treatment of Patients With Metastatic Breast,Lung, and Prostate Cancer: A Meta-Analysis

The purpose of this meta-analysis was to investigate whether bisphosphonates are a key therapy for bone metastases in lung cancer, breast cancer, and prostate cancer by comparing all randomized controlled trials that appraised the effects of bisphosphonates on risk of skeletal-related events (SREs).PubMed, Embase, and Medline databases (up to December 2014) were used to search all related articles. Using the data from 19 available publications, the authors examined the efficacy in treating or reducing the risk of SREs in lung cancer, breast cancer, and prostate cancer by meta-analysis.Bisphosphonates have demonstrated efficacy in treating or reducing the risk of SREs in lung cancer [odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.69–0.95, P = 0.008], breast cancer (OR = 0.62, 95% CI = 0.54–0.71, P = 0.000), and prostate cancer (OR = 0.62, 95% CI = 0.45–0.86, P = 0.004).This meta-analysis suggests that bisphosphonates have demonstrated efficacy in treating or reducing the risk of SREs in lung cancer, breast cancer, and prostate cancer.