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Autoimmune atrophic gastritis (AAG) is associated with an increased risk of certain types of gastric cancer (GC). Helicobacter pylori (H. pylori) infection may have a role in the induction and/or maintenance of AAG and GC. Toll-like receptors (TLR) are essential for H. pylori recognition and subsequent innate and adaptive immunity responses. This study therefore aimed to characterize TLR polymorphisms, and features of bacterial flagellin A in samples from patients with AAG (n = 67), GC (n = 114) and healthy donors (HD; n = 97). TLR5 rs5744174 C/C genotype was associated with GC, lower IgG anti H. pylori response and a higher H. pylori flagellin A abundance and motility. In a subset of patients with AAG, H. pylori strains showed a reduction of the flagellin A abundance and a moderate motility compared with strains from GC patients, a prerequisite for active colonization of the deeper layers of the mucosa, host immune response and inflammation. TLR9 rs5743836 T allele showed an association with serum gastrin G17. In conclusion, our study suggests that alterations of flaA protein, moderate motility in H. pylori and two polymorphisms in TLR5 and TLR9 may favor the onset of AAG and GC, at least in a subset of patients. These findings corroborate the function of pathogen–host cell interactions and responses, likely influencing the pathogenetic process.

Autoimmune atrophic gastritis (AAG) is associated with an increased risk of certain types of gastric cancer (GC). Helicobacter pylori (H. pylori) infection may have a role in the induction and/or maintenance of AAG and GC. Toll-like receptors (TLR) are essential for H. pylori recognition and subsequent innate and adaptive immunity responses. This study therefore aimed to characterize TLR polymorphisms, and features of bacterial flagellin A in samples from patients with AAG (n = 67), GC (n = 114) and healthy donors (HD, n = 97). TLR5 rs5744174 C/C genotype was associated with GC, lower IgG anti H. pylori response and a higher H. pylori flagellin A abundance and motility. In a subset of patients with AAG, H. pylori strains showed a reduction of the flagellin A abundance and a moderate motility compared with strains from GC patients, a prerequisite for active colonization of the deeper layers of the mucosa, host immune response and inflammation. TLR9 rs5743836 T allele showed an association with serum gastrin G17. In conclusion, our study suggests that alterations of flaA protein, moderate motility in H. pylori and two polymorphisms in TLR5 and TLR9 may favor the onset of AAG and GC, at least in a subset of patients. These findings corroborate the function of pathogen&ndash, host cell interactions and responses, likely influencing the pathogenetic process.

Thyrotropin (TSH) is the most accurate marker of thyroid dysfunction in the absence of pituitary or hypothalamic disease. Studies on TSH reference intervals (RIs) showed wide inter-individual variability and prompted an intense debate about the best estimation of TSH RIs. We performed a population study on TSH RIs, using current data stored in the laboratory information system (LIS), at the Hospital Department of Laboratory Medicine, Pordenone (Italy), historically an area of mild–moderate iodine deficiency with a relatively high goiter prevalence. 136,650 individuals constituted the final sample. A TSH immunoassay was performed on fasting serum samples with the Dimension Vista 1500 analyzer (Siemens Healthineers). We adopted the Kairisto’s procedure to analyze TSH data downloaded by the LIS, applying the indirect strategy for deriving RIs. TSH RIs of the entire population were 0.32–3.36 mIU/L with a distribution skewed towards higher values. RIs were 0.26–3.61 mIU/L for females, and 0.32–3.01 mIU/L for males. Unlike other studies, TSH median levels progressively decreased from 0–4 to 85–104 years in the overall population, both in male and in female subgroups, showing an inverse correlation between TSH and age in all groups. This study is the first to analyze a high percentage (40%) of individuals from an ethnically homogenous Caucasian population. The results obtained emphasize the opportunity to define the TSH RIs according to age, gender and race, in addition to assay methods, and provide further insight about the possible role of iodine status.

OBJECTIVES: The objectives of this study were to investigate the serum pepsinogen test for the prediction of OLGIM (Operative Link on Gastric Intestinal Metaplasia Assessment) stages in first-degree relatives (FDR-GC) of patients with gastric cancer (GC) and autoimmune chronic atrophic gastritis (ACAG).METHODS: In 67 consecutive patients with ACAG, 82 FDR-GC, and 53 controls (CTRL) without gastric disease (confirmed by biopsy), serum levels of pepsinogen 1 (PG1), pepsinogen 2 (PG2), G17, and the PG1/2 ratio were assessed by enzyme-linked immunosorbent assay kit. All ACAG patients had positive antiparietal cell antibody levels, estimated by indirect immunofluorescence. Biopsies taken in duplicate from the antrum, corpus, and fundus were stained with Giemsa for Helicobacter pylori detection. Endoscopic detection of metaplasia was confirmed by histological diagnosis. Histological classification of OLGIM stages was applied by using the criteria of severity and topography of intestinal metaplasia (IM).RESULTS: The highest discrimination capacity for distinguishing ACAG from other groups of patients was the gastrin G17 test. The lowest mean for PG1 and PG2 serum levels was found in ACAG. In multivariate analysis by age, PG1 and PG1/PG2 were independent prognostic factors for metaplasia, and PG2 also for the presence of a histological H. pylori infection. The serum PG1 level was significantly lower in individuals with IM at OLGIM stage >2 than in those with IM at OLGIM stage = 2 vs. 0-1 OLGIM stages, the receiver operating characteristic (ROC) curve at 47.9 ng/ml PG1 level reached a significant area under the curve (AUC) value (0.978, P= 2. Using a cutoff of 47.9 ng/ml, PG1 testing in FDR-GC and ACAG patients had a sensitivity of 95.83% and a specificity of 93.37. Although these results could be validated in a prospective study, the known importance of higher OLGIM stages in increasing the risk of GC development supports the rationale of proposing PG1 algorithm as a diagnostic tool for the selection of high-risk FDR-GC and ACAG patients at high-risk stages for subsequent detailed endoscopic examination to detect dysplasia and asymptomatic GC. In addition, serum PG1 and PG2 levels could stratify patients based on both H. pylori infection and OLGIM risk in consideration of the increased acknowledge regarding the role of H. pylori in the progression of gastritis to GC.

OBJECTIVE—To evaluate the rate of progression of renal disease in proteinuric type 2 diabetic patients with and without retinopathy. RESEARCH DESIGN AND METHODS—Thirty-eight proteinuric type 2 diabetic patients with diabetic retinopathy and 27 without were enrolled in an observational study for the evaluation of rate of glomerular filtration rate (GFR) decline and followed up for a median period of 6 years. GFR was determined at least once per year, and blood pressure, glycated hemoglobin, and proteinuria were determined every 4 months. RESULTS—Although the two groups had comparable GFR, albuminuria, blood pressure, and HbA1c at entry of the study, the rate of decline of GFR was higher in type 2 diabetic patients with retinopathy (−6.5 ± 4.4 ml/year) than in those without (−1.8 ± 4.8 ml/year; P < 0.0001). Protein and albumin excretion rate increased significantly in patients with retinopathy, while they did not change in those without. Mean blood pressure between the two groups of patients were similar both at entry and during the follow-up, although the proportion of patients treated with at least two antihypertensive drugs was higher in patients with retinopathy. On a multiple regression analysis, only mean blood pressure and proteinuria were significant determinants of progression of renal disease in type 2 diabetic patients with retinopathy. CONCLUSIONS—The rate of progression of renal disease in proteinuric type 2 diabetic patients with retinopathy is faster than that observed in those without retinopathy. The screening for retinopathy identifies patients at high risk for rapid deterioration of kidney function.