-765G＞C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia

INTRODUCTION Gastric adenocarcinoma mortality rates have been decreasing in Europe[1], although, in Portugal it still remains one of the leading causes of cancer-related deaths (third in men and fourth in women). Portugal has one of the highest mortality …     

Can parathyroid hormone be used as a biomarker for heart failure?

Secondary hyperparathyroidism in heart failure is a consequence of renin–angiotensin–aldosterone activation, chronic hyperaldosteronism, and loop diuretic usage, resulting in calcium excretion. The result is an inflammatory state with adverse effects on myocardial remodeling and systemic complications. Recent literature has suggested that elevated parathyroid hormone predicts adverse outcomes in patients with heart failure independent of serum calcium and phosphate, vitamin D deficiency, and renal insufficiency. Parathyroid hormone has been correlated with elevated brain natriuretic peptide levels, an established biomarker of heart failure severity. There are several limitations to the utilization of parathyroid hormone as a biomarker for heart failure, and further prospective studies need to be conducted to assess the value of multiple parathyroid hormone measurements over time and elucidate the role of parathyroid hormone in diastolic dysfunction. Pending further validation, there is promise for parathyroid hormone as a complementary biomarker in heart failure.     

Does eradication of Helicobacter pylori reverse atrophic gastritis or intestinal metaplasia? Data from Japan

In Japan, more reports showing improvement of atrophy or IM after eradication have appeared than reports showing no change. Many authors take biopsy specimens from the lesser and greater curvatures of the antrum and body and incisura angularis and make a histologic assessment using the standardized Updated Sydney System. Sampling errors should be taken into account, however. Interobserver agreement is poor in grading of atrophy. Apart from these problems, it seems almost certain that some patients show improvement or regression of atrophy or IM after eradication. Takizawa et al, evaluating many gastritis specimens, observed that antral IM might regress after eradication in the antral mucosa, where some pyloric glands remained under IM because pyloric glands and IM shared the proliferative zone, and that body IM replacing total fundic glands might hardly regress (T. Takizawa, MD, personal communication). Suto et al showed in an animal model that pseudopyloric glands differentiated into chief and parietal cells. Watanabe et al examined the influence of gastric pH on IM in x-irradiated rats and showed that increased acid secretion was associated with partial disappearance of IM without Paneth cells. Because gastric acid secretion of hypochlorhydric patients with body-predominant gastritis increased into normal range 1 to 6 months after eradication, it is possible that IM may regress in human subjects whose acid-secreting capacity recovers after eradication. The point of no return at which eradication leads to regression of atrophy and IM is not known. It is unknown how long IM takes to regress after eradication. There may be some differences in the characteristics between patients with and without improvement. Factors other than H. pylori (e.g., environmental factors) also should be investigated.     

The correlation between histological gastritis staging- ‘OLGA/OLGIM’ and serum pepsinogen test in assessment of gastric atrophy/intestinal metaplasia in China

Background: Serum pepsinogen (PG) test, as an indicator of gastric mucosal atrophy, reflects the functional and morphologic status of gastric mucosal and it is suggested to serve as a useful predictive marker for patients with gastric cancer (GC). The available classifications of gastritis, known as the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Intestinal Metaplasia (OLGIM), integrating the severity and topography of atrophy/intestinal metaplasia (IM), have been gradually accepted and used in screening for GC in recent years.

Goals: To assess whether serum pepsinogen test, including PGI, PGII, PGI/PGII and gastrin-17 (G-17) could reflect the extent and topography of gastric mucosal atrophy/IM. Furthermore, to discuss the relationship between OLGA/OLGIM staging system and serum pepsinogen test in assessment of gastric atrophy/IM.

Methods: The OLGA/OLGIM ranks the gastric staging according to both the topography and the severity of gastric atrophy/IM. A retrospective study was conducted with 331 patients who underwent endoscopy with consecutive biopsy sampling and reassessed according to OLGA/OLGIM staging system. Serum pepsinogen test, including PGI, PGII, PGI/PGII and G-17, as well as serological Helicobacter pylori (Hp) antibody were also measured. Results were presented as gastritis stage, serum pepsinogen level and Hp status. Baseline characteristics were compared using analysis of variance (ANOVA) test for continuous data and Pearson’s χ² test for categorical data. A logistic regression model was used for the correlation analysis between OLGA/OLGIM and serological pepsinogen test.

Results: A total of 177 non-atrophic gastritis and 154 atrophic gastritis were analyzed, among which 40 were antrum atrophy, 32 were corpus atrophy and 82 were pan-atrophy. All patients were assessed applying the OLGA/OLGIM criteria with a mean age of 54.7?±?10.8 years. Patients among OLGA/OLGIM Stage III–IV were presented with a lower level of serum PGI and PGI/PGII (p?<?.05), especially for Stage IV (p?=?.01). For both Hp-positive patients and Hp-negative patients according to OLGA system, PGI/PGII level correlated inversely with the rising stage (p?=?.022; p?=?.028). As for OLGIM system, similar difference can be seen in PGI/PGII level in either Hp-positive patients, or Hp-negative patients (p?=?.036; p?=?.013). In addition, the percentage of G-17 <1?pmol/L combined with PG-negative in antrum atrophy group was much higher than that of non-atrophy group and corpus atrophy group (25 versus 15.8 versus 6.3%) (p?=?.029). The proportion of G-17?>?15?pmol/L combined with PG-positive was apparently higher in corpus atrophy group, compared with other two groups (25 versus 11.3 versus 8.1%) (p?=?.023). Logistic regression modeling showed there exist significant connections between OLGA/OLGIM stages and serum pepsinogen test in patient stratification for gastric mucosal atrophy assessment (p?<?.001, p?<?.001).

Conclusions: Serum pepsinogen test has a strong correlation with OLGA/OLGIM gastritis stage and could provide important information in assessment of atrophy/intestinal metaplasia.     

Can endocan be a new biomarker in ventilator-associated pneumonia?

Ventilator-Associated Pneumonia (VAP) is a hospital-acquired bacterial infection with high incidence and mortality rate. The aim of this study is to investigate the correlation between the Endocan level and development of VAP and whether or not this correlation was correlated with the clinical findings. Demographic data, white blood cell (WBC) count, procalcitonin (PCT), c-reactive protein (CRP), and fever levels of 60 patients were recorded in serial measurements for 5 days. When there was the presence of fever or elevated Endocan, alveolar lavage culture was taken and chest radiographies were taken. Correlations of the Endocan levels with the culture results and laboratory values were examined. The rate of VAP was found as 10.4/1000 mechanical ventilator days. Endocan levels were significantly higher in patients with VAP (p < 0.05). However, there was no significant difference among PCT, WBC, CRP measurements (p > 0.05). No correlation was found between Endocan levels and PCT, WBC and CRP levels in those with VAP (p > 0.05). A significant correlation was found between the Endocan level and the elevated fever 24 h later (p:0.001). The serum Endocan level on the day 3 had a specificity of 73.3%, a sensitivity of 68.9%, positive predictive value of 44%, and negative predictive value of 88.5% at the cut off level of 9.17 ng/mL. In this study, it was determined that high Endocan levels were associated with the development of VAP. The present study suggested that Endocan can be used as a screening tool for the development of VAP.

Can YKL-40 be used as a biomarker for interstitial lung disease?: A systematic review and meta-analysis

Background:Interstitial lung disease (ILD) has a poor prognosis and lacks specific biomarkers for early diagnosis, assessment of disease severity, and prognosis. YKL-40 levels were found to be elevated in patients with ILD, but these results are inconsistent. Therefore, we conducted a systematic review and meta-analysis to accurately study the relation between YKL-40 and ILD.Methods:We performed a systematic literature search in many databases (PubMed, Embase, the China National Knowledge Infrastructure, and Wanfang databases) and commercial Internet search engines to identify studies involving the role of YKL-40 in patients with ILD. The weighted mean difference with its 95% confidence interval were used to investigate the effect sizes. If obvious heterogeneity was found in the meta-analysis, the level of YKL-40 was directly compared by the Mann-Whitney test.Results:Sixteen eligible articles were finally identified. The results showed that the serum YKL-40 levels of patients with idiopathic pulmonary fibrosis, connective tissue-related ILD, sarcoidosis, cryptogenic tissue pneumonia, asbestosis-ILD, and idiopathic nonspecific interstitial pneumonia were higher than those in controls, but there was no increase in patients with pulmonary alveolar proteinosis. We also found that there are certain differences in the serum YKL-40 levels in patients with different types of ILD. The results showed that the bronchoalveolar lavage fluid YKL-40 levels of patients with idiopathic pulmonary fibrosis were significantly higher than that in controls. A systematic review indicated that there were correlations between the serum YKL-40 levels and lung function in patients with different ILD. In addition, YKL-40 may be used as a valuable biomarker for survival, with risk ratios ranging from 1.006 to 10.9.Conclusions:This study suggests that YKL-40 may be a useful biomarker for the diagnosis and prognosis of ILD.     

Can miRNA712＿3p be a promising biomarker for early diagnosis of toxoplasmosis?

Objective: To assess the role of miRNA712_3p as a specific biomarker in early detection of toxoplasmosis in plasma of mice acutely infected with Toxoplasma gondii. Methods: Real-time PCR was used to measure the level of miRNA712_3p in plasma of infected mice. Immunecompetent and immune-suppressed mice were examined, three and five days post-infection. Results: Results revealed significant up-regulation of plasma miRNA712_3p in both immunecompetent and immune-compromised groups in comparison to the control non-infected group. Additionally, an increase in the level of miRNA712_3p was noticed correspondently in the parasite density detected in liver impression smears. Conclusions: miRNA712_3p can be used as a novel biomarker for the detection of Toxoplasma gondii infection in both immunecompetent and immune-compromised host.     

Can platelet BACE1 levels be used as a biomarker for Alzheimer's disease? Proof-of-concept study

To date there is no validated peripheral biomarker to assist with the clinical diagnosis of Alzheimer's disease (AD). Platelet proteins have been studied as AD biomarkers with relative success. In this study, we investigated whether platelet BACE1 levels differ between AD and cognitively normal (CN) control patients. Using a newly developed ELISA method, we found that BACE1 levels were significantly lower in AD compared to CN subjects. These data were supported by the observation that several BACE1 isoforms, identified by Western blotting, were also lower in AD platelets. This proof-of-concept study provides evidence for testing platelet BACE1 levels as a peripheral AD biomarker using a novel, sensitive and inexpensive method.     

Endoscopic grading of gastric atrophy and histological gastritis staging on risk assessment for early gastric cancer: A case–control study

Objectives

To assess the predictive value of endoscopic grading of gastric atrophy using Kimura–Takemoto classification, histological grading systems of operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) on risk stratification for early gastric cancer (EGC) and other potential risk factors of EGC.

Methods

A single-center, case–control study was retrospectively conducted including 68 patients with EGC treated with endoscopic submucosal dissection and 68 age- and sex-matched control subjects. Kimura–Takemoto classification, OLGA and OLGIM systems, and other potential risk factors were evaluated between the two groups.

Results

Of the 68 EGC lesions, 22 (32.4%) were well differentiated, 38 (55.9%) were moderately differentiated, and 8 (11.8%) were poorly differentiated, respectively. Multivariate analysis revealed O-type Kimura–Takemoto classification (adjusted odds ratio [AOR] 3.282, 95% confidence interval [CI] 1.106–9.744, P = 0.032) and OLGIM stage III/IV (AOR 17.939, 95% CI 1.874–171.722, P = 0.012) were significantly related to a higher risk of EGC. Especially, O-type Kimura–Takemoto classification within 6–12 months before EGC diagnosis (AOR 4.780, 95% CI 1.650–13.845, P = 0.004) was independently associated with EGC risk. Areas under the receiver operating characteristic curve of the three systems for EGC were comparable.

Conclusions

Endoscopic Kimura–Takemoto classification and histological OLGIM stage III/IV are independent risk factors for EGC, which may reduce the need for biopsies in risk stratification of EGC. Further multicenter prospective studies of large sizes are needed.     

Can the diagnosis of NSAID-induced or Hp-associated gastric ulceration be predicted from histology?

We studied the question whether NSAID/ASA-induced ulcerations can be identified in human gastric biopsy material on the basis of ischaemic necrosis. Biopsies of 208 patients with gastric ulcers were assessed histologically. 29 patients were excluded from the study. NSAID/ASA ulcers were diagnosed when a homogeneous eosinophilic ischaemic necrosis was found. Helicobacter pylori-(Hp-) induced ulcers were diagnosed when non-homogeneous fibrinoid necrotic material containing granulocytes and cell debris was noted. The histological diagnosis was compared with the data on medication use, endoscopy and clinical history. 121 of the 179 patients included had a medical history on NSAIDS/ASA. From the 60 patients taking NSAIDS/ASA with no histologic evidence of Hp all (100 %) were identified by the histology of the necrosis. From the 61 patients taking NSAID/ASA and histologic evidence of H. pylori 40 (66 %) were identified by histology. From the 58 patients with no such medication 41 were Hp-positive and correctly identified by histology in 31 cases (76 %). The sensitivity of the histologic diagnosis of NSAID/ASA-induced ulceration was 85 %, and its specificity 53 %. The results of our study show that a high percentage of the NSAID/ASA-induced ulcers of the stomach can indeed be correctly diagnosed at histology. In conclusion the underlying aetiopathogenesis of gastric ulcerations (NASID/ASA vs. Hp) can be uncovered in a large proportion of patients based on histological examination.     

Could mean platelet volume be a promising biomarker of progression of chronic kidney disease?

The mean platelet volume (MPV), a readily available indicator of platelet activation and function, is a useful predictive and prognostic biomarker of cardiovascular and cerebrovascular disease (CVD). It is associated with a variety of prothrombotic and proinflammatory diseases. Larger platelets are more likely to aggregate and release greater quantities of adhesive molecules. MPV has seldom been investigated in patients with chronic kidney disease (CKD). This study aimed to investigate the relationship between MPV levels and the glomerular filtration rate (GFR) in patients with CKD. We reviewed the medical records of patients with CKD who visited the nephrology outpatient clinics of Soonchunhyang University Bucheon Hospital between January 2010 and May 2013. A total of 553 patients were included in the present retrospective study. According to the estimated GFR (eGFR) calculated by the abbreviated the Modification of Diet in Renal Disease (MDRD) equation, the patients were allocated to Group 1 (GFR, 60–89?ml/minute/1.73?m²; n?=?64), Group 2 (GFR, 30–59?ml/minute/1.73?m²; n?=?268), Group 3 (GFR, 15–29?ml/minute/1.73?m²; n?=?147), or Group 4 (GFR, <15?ml/minute/1.73?m² and non-dialysis; n?=?74). Data were analyzed by Student’s t-test, the chi-squared test, Pearson’s correlation coefficient (r), Tukey’s honestly significant difference (HSD) test, and one-way analysis of covariance. The MPV values had a negative correlation with eGFR in patients with CKD (Pearson’s correlation coefficient?=??0.553, p?<?0.001). The mean MPV values in Groups 1–4 were 9.81?±?0.13?fl, 10.34?±?0.08?fl, 10.86?±?0.09?fl, and 11.19?±?0.11?fl, respectively (p?<?0.001). Multiple comparisons of MPV values in the four groups by Tukey’s HSD test showed statistically significant intergroup differences, with all p values <0.001. Platelet counts and PDW decreased along with eGFR, and there were no significant differences with respect to plateletcrit. Patients with prevalent coronary artery disease (CAD) or CVD had higher MPVs than did those without CAD or CVD. MPV was significantly increased with progression of CKD. MPV may be a useful indicator of increased risks of CAD or CVD in patients with CKD.     

Antral-type mucosa in the gastric incisura, body, and fundus (antralization): a link between Helicobacter pylori infection and intestinal metaplasia?

OBJECTIVES: Helicobacter pylori is a carcinogen; gastric carcinoma involves a multistep process from chronic gastritis to atrophy, intestinal metaplasia, and dysplasia. The aims of this study were to determine the types of mucosa at different gastric sites in H. pylori-infected and uninfected patients, and whether the presence of antral-type mucosa in the incisura, body, and fundus is associated with gastric atrophy and intestinal metaplasia. METHODS: Two hundred and sixty-eight patients with dyspepsia were enrolled. Eight biopsies (i.e., antrum x3, body x2, fundus x2, and incisura x1) were obtained. One antral biopsy was used for the CLO-test. Three (each from the antrum, body, and fundus) were cultured. The remaining biopsies were examined histologically according to the updated Sydney System after staining with hematoxylin and eosin and Giemsa. A validated serological test was also applied. RESULTS: Overall, 113 (42%) patients were infected with H. pylori. At the incisura, antral-type mucosa was more prevalent in infected than in uninfected patients (84% vs. 18%; odds ratio [OR] = 23.9, 95% confidence interval [CI] 12.5-45.8; p<0.001). Atrophic gastritis and intestinal metaplasia at the incisura was present in 19.5% and 13.3%, respectively, of infected, and 4.5% and 3.2%, respectively, of uninfected patients (both p<0.01). Moreover, atrophic gastritis at the incisura was associated with the presence of antral-type mucosa at the site (termed antralization); the prevalence of atrophic gastritis was 19.5% (24/123) in the presence of antralization, whereas the rate was 2.1% (3/145) without antralization (OR = 11.4, 95% CI 3.4-39.2; p<0.001). Similarly, at the incisura, 16.3% (20/123) of "antralized" cases and 1.4% (2/145) of "unantralized" cases had intestinal metaplasia (OR = 13.8, 95% CI, 3.2-60.7; p<0.001). The association between antralization at gastric body and fundus also appeared to be associated with atrophic gastritis and intestinal metaplasia at these sites. CONCLUSIONS: Atrophic gastritis and intestinal metaplasia occurs predominantly at the gastric antrum and incisura with H. pylori infection. Antralization of the gastric incisura is a common event in H. pylori-infected patients, and appears to be associated with an increased risk of atrophic gastritis and intestinal metaplasia.