Differential Reactivation of Cytomegalovirus and Epstein-Barr Virus in Patients with B Cell Lymphoma.

Although cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are considered latent viruses, their reactivation occurs in immunosuppressed conditions. We previously reported that CMV and EBV are reactivated in patients receiving immunosuppressive therapy and/or chemotherapy. This retrospective, single-center study aimed to determine the frequency of viral reactivation and clinical characteristics of patients with B cell lymphoma (B-ML) receiving chemotherapy. Twenty-four patients (mean age 73 years, range 40-87 years; male-to-female ratio, 15:9) with diffuse large B cell lymphoma (n = 15), follicular lymphoma (n = 8), or mantle cell lymphoma (n = 1) were enrolled. Serum CMV and EBV DNA levels were analyzed using quantitative real-time polymerase chain reaction in patients with B-ML receiving chemotherapy. We determined the cumulative reactivation of each virus and analyzed the relationship between viral reactivation and clinical characteristics. Three patients experienced relapse or refractory (R/R) disease and the others had de novo lymphomas. The frequencies of CMV and EBV reactivations were 54.2% and 37.5%, respectively. CMV reactivation occurred significantly earlier during chemotherapy courses in R/R patients than in de novo patients (p = 0.0038), while EBV reactivation was frequently found before treatment. Baseline serum levels of soluble interleukin-2 receptor were higher (4318.0 vs. 981.1 U/mL, p = 0.010) and hemoglobin levels were lower (11.1 vs. 13.0 g/dL, p = 0.0038) in patients with EBV reactivation than in those without reactivation. These findings were not observed in patients with CMV reactivation. CMV reactivation was associated with iatrogenic immunosuppression, whereas EBV reactivation was related to immunosuppression by lymphoma, indicating that the mechanisms of these viral reactivations differed.

Construction of an Automatic Quantification Method for Bone Marrow Cellularity Using Image Analysis Software.

Although rapid, the evaluation of bone marrow (BM) cellularity is semi-quantitative and largely dependent upon visual estimates. We aimed to construct an automatic quantification method using image analysis software. We used hematoxylin and eosin (HE)-stained specimens of BM biopsies and clots from patients who underwent BM examination at Tottori University Hospital from 2020 to 2022. We compared image analysis (Methods A, B, and C) with visual estimates in pathology reports of 91 HE specimens in 54 cases (29 males, 25 females), including 38 biopsy and 53 clot specimens. Cellularity was visually scored as hypocellular (n = 17), normocellular (n = 44), or hypercellular (n = 30). Compared with the visual estimates, intraclass correlation coefficients for Methods A, B, and C were 0.80, 0.85, and 0.88, respectively. The most appropriate values were obtained with Method C which detected both non-fatty and cell nuclear areas.

Fibrin monomer complex as a potential thrombosis marker related to venous thromboembolism risk in pregnant women.

BACKGROUND: Pregnancy is a risk factor for venous thromboembolism (VTE) due to increased coagulation factor activity and decreased protein S activity. However, thrombosis markers for predicting VTE in pregnancy remain controversial. This study aimed to investigate the relationship between VTE risk and thrombosis markers in pregnant women and to identify markers related to VTE risk. METHODS: Archived plasma samples from 107 pregnant women were used in this study, and the concentrations of D-dimer, fibrin monomer complex (FMC), plasmin-plasmin inhibitor complex, prothrombin time, activated partial thromboplastin time, and fibrinogen were measured. VTE risk was scored according to the Royal College of Obstetricians and Gynaecologists green-top guidelines and the patients were divided into low- or high-risk groups. RESULTS: The median (range) of risk score for deep vein thrombosis was 2 (0-8), and we defined the high-risk group included those with a score of ≧3. D-dimer and FMC concentrations were significantly higher in the high-risk group than in the low-risk group (D-dimer 4.5 vs 2.6 µg/mL, p = 0.008; FMC 14.6 vs 3.4 µg/mL, p < 0.001). Although D-dimer concentration significantly increased with gestational age (Spearman's correlation coefficient [rs] = 0.317, p < 0.001), FMC concentration did not (rs = -0.081, p = 0.409). The area under the receiver operating characteristic curve values of D-dimer, FMC, and both D-dimer and FMC for the high-risk group were 0.656, 0.713, and 0.738, respectively. CONCLUSIONS: FMC may be a thrombosis marker related to VTE risk in pregnancy and is potentially preferable over D-dimer concentrations.

Differences in the Composition of Activated Partial Thromboplastin Time (APTT) Reagents Affect Clot Waveform Analysis.

Background: Clot waveform analysis (CWA) based on activated partial thromboplastin time (APTT) is a useful assay for hemostasis. However, the effects of activators and phospholipid conditions on CWA have not been adequately investigated. Therefore, we characterized CWA using four different APTT reagents. Methods: We used 39 archived plasma samples from patients with hemophilia A (HA), 16 samples from patients with HA under emicizumab treatment, and 10 samples from healthy individuals for CWA with four different types of APTT reagents (reagents A, B, C, and D). We then compared Ad|min1|, Ad|min2|, and Ad|max2| from the CWA, which reflect the maximum velocity, maximum acceleration, and maximum deceleration, respectively, among the four reagents. Results: Similar clot waveform shapes were observed for each reagent in the healthy donor group, HA group, and HA under emicizumab group, and the waveform was different for each target group. Significant changes were found in clotting time (CT) (s), Ad|min1| (%/s), Ad|min2| (%/s2), and Ad|max2| (%/s2). The waveform pattern for the coagulation reaction by reagent D, comprising silica and synthetic phospholipids, was the fastest among the reagents examined. Further, the difference in Ad|min1| (%/s) and Ad|min2| (%/s2) was larger than that in CT depending on the reagent used(s), indicating that the measured value of CWA was affected by the reagent composition. Conclusion: Our results showed a significant difference among reagents with varying composition and concentration; this was found to affect the parameters obtained from CWA. Thus, the differences between reagents hinder standardization of quantitative evaluation using these parameters; further, this highlights the necessity of understanding the characteristics of APTT reagents and determining the reference range in individual facilities.

Regression Analysis to Estimate the Factor VIII Activity of Patients with Hemophilia A Without Inhibitor who Received Emicizumab Therapy.

BACKGROUND: Emicizumab, a bispecific monoclonal antibody for hemophilia A (HA), has strong pharmacodynamic effects in several coagulation assays resulting in dosing difficulties with Factor VIII (FVIII) concentrates during bleeding emergencies. MATERIALS AND METHODS: Single and multiple regression models were studied to estimate FVIII activity using 27 archived plasma samples from three patients with HA without inhibitor under emicizumab treatment. Explanatory variables were FVIII chromogenic assay (CSA), Ad|min1|, Ad|min2|, the number of seconds of APTT, and the FVIII one-stage assay (OSA), which were measured without idiotype antibodies. The response variable was FVIII OSA measured with idiotype antibodies. RESULTS: In the simple linear model, the FVIII CSA regression coefficient was 1.04 and the intercept was -14.55 (r2 = 0.95; p < 0.001). In the multiple regression model, FVIII OSA and FVIII CSA were selected based on the Akaike Information Criterion, with regression coefficients of 1.74 and 1.15, respectively, and an intercept of -92.03 (r2 = 0.96, p < 0.001). CONCLUSIONS: The regression models can estimate the FVIII:C levels in patients with HA receiving emicizumab and would be useful in a bleeding emergency and/or surgery.

Clinical Characteristics and Predictors Related to the Progression of Multinodular Goiter Causing Tracheal Compression and Deviation: A Report of Two Cases and Review of the Literature.

We describe the clinical course of two patients who developed tracheal compression and deviation by multinodular goiter (MNG). Case 1: A 66-year-old woman presented with thyroid swelling. Five years after the initial admission, she was diagnosed with hyperthyroidism by Graves' disease and increased bilateral thyroid lobes compressing the trachea. Thyroglobulin was elevated from 210 to 472 ng/mL. Case 2: A 52-year-old woman presented with thyroid swelling. Five years after the initial admission, the increased right lobe deviated the trachea and compressed the right recurrent laryngeal nerve. Thyroglobulin was elevated from 122 to 392 ng/mL. Two cases and literature review indicated that MNG with >50 mm, solid components, and extension to the mediastinum or paralarynx were risk factors of tracheal compression and deviation. Monitoring thyroglobulin elevation can help predict the clinical course.

Eradication therapy for Helicobacter pylori infection improves nutrition status in Japanese hemodialysis patients: a pilot study.

Plasma ghrelin level is influenced by Helicobacter pylori (H. pylori) status and the severity of gastric mucosal atrophy, and the ghrelin level is associated with nutrition status in hemodialysis patients. Here, we investigated the efficacy of H. pylori eradication therapy in improving nutrition status in relation to the ghrelin level in H. pylori-positive hemodialysis patients. Of H. pylori-positive patients receiving hemodialysis at 8 dialysis center, 21 patients underwent gastroduodenoscopy for evaluation of the severity of gastric atrophy, and nutrition markers and plasma ghrelin levels before and 1 year after H. pylori eradication therapy were evaluated. Serum cholinesterase level was significantly increased after H. pylori eradication compared with the level before eradication (303.2 ± 76.0 vs 287.3 ± 68.1 IU/L, p = 0.029). In particular, cholesterol (before, 196.6 ± 23.2 mg/dl; after, 206.1 ± 25.9 mg/dl, p = 0.042) and cholinesterase levels (before, 296.9 ± 70.8 IU/L; after, 316.4 ± 73.8 IU/L, p = 0.049) increased more strongly in patients with mild-moderate atrophy than those with severe atrophy, irrespective of improvement of plasma acyl-ghrelin and desacyl-ghrelin levels after eradication therapy. In conclusion, H. pylori eradication may improve nutrition status by increasing serum cholinesterase and cholesterol levels in hemodialysis patients, especially those with mild and moderate gastric mucosal atrophy.

Gender Differences in Plasma Ghrelin Levels in Hemodialysis Patients.

Ghrelin is an orexigenic hormone mainly secreted by the stomach, and it decreases according to the severity of gastric atrophy. Ghrelin has multiple favorable functions, including protein anabolism enhancement, anti-inflammatory activity, and cardiovascular protection, and is associated with survival in hemodialysis (HD) patients. Although the plasma level and role of ghrelin may be different depending on gender, they have not been completely assessed in HD patients. We enrolled 80 (male/female: 51/29) maintenance HD patients. An upper gastrointestinal endoscopic examination was performed for all patients to determine the severity of gastric mucosal atrophy and Helicobacter pylori infection. We measured plasma acyl and desacyl ghrelin levels and assessed the association between ghrelin levels and relevant clinical parameters, including nutrition, inflammation, atherosclerosis, and bone metabolism, by gender. Both acyl and desacyl ghrelin levels in female HD patients were significantly higher than those in male HD patients. When stratified by gastric mucosal atrophy, these gender differences were observed only in patients without gastric atrophy. In female patients, acyl ghrelin level was negatively correlated with age. In male patients, both acyl and desacyl ghrelin levels were positively correlated with bone mineral density. Multiple regression analysis showed significant positive correlations between both ghrelin levels and female gender after adjusting for confounding factors. Plasma ghrelin levels were higher in female HD patients than in male HD patients. The gender difference was more evident in patients without gastric atrophy.

Efficacy of Reduced Dosage of Amoxicillin in an Eradication Therapy for Helicobacter pylori Infection in Patients on Hemodialysis: A Randomized Controlled Trial.

BACKGROUND: An optimum Helicobacter pylori-eradication regimen for hemodialysis patients is yet to be established because of different pharmacokinetics of amoxicillin involved between hemodialysis patients and healthy subjects. We investigated to establish appropriate doses of amoxicillin for H. pylori infection eradication in hemodialysis patients. METHODS: Of 409 hemodialysis patients screened for H. pylori infection, 37 H. pylori-positive patients were randomized to different 1-week eradication regimens: esomeprazole 20 mg twice a day (b.i.d.) and clarithromycin 200 mg b.i.d., plus amoxicillin at either 750 mg b.i.d. (group A; conventional) or 250 mg b.i.d. (group B; experimental). Sixty-three patients with normal renal function received the conventional regimen (group C). Successful eradication was confirmed by urea breath testing. RESULTS: Eradication rates of group B (reduced amoxicillin-regimen) were 84.2% in intention-to-treat analysis and 88.9% in per-protocol analysis, which were similar with group A (77.8 and 77.8%) and group C (74.6 and 81.0%). However, the incidence of adverse events in group A was significantly higher than that in group C (22.2 vs. 5.1%, p = 0.027). CONCLUSIONS: In H. pylori-positive hemodialysis patients, amoxicillin at 250 mg b.i.d. may be an appropriate scheme for eradication with equivalent effects to the conventional therapy and safety effects for adverse events.

Natural Course of Helicobacter pylori Infection in Japanese Hemodialysis Patients.

INTRODUCTION: Helicobacter pylori (H. pylori) infection is one of the major risk factors for gastrointestinal morbidity in hemodialysis patients. Primary end point is to investigate H. pylori infection rate in hemodialysis patients. As secondary end point, we clarified whether pepsinogen (PG) level was related with H. pylori infection status in hemodialysis patients. METHODS: Serum levels of PG I, II, and anti-H. pylori IgG antibody were assessed in 500 Japanese hemodialysis patients. RESULTS: H. pylori infection rate was 15.0% (75/500; 95% CI 12.0-18.4). The duration of hemodialysis in H. pylori-positives was 4.6 ± 3.8 years, which was significantly shorter than in H. pylori-negatives (7.3 ± 6.9, p = 0.001). PG I levels positively correlated with the PG II level and PG I/II ratio (|R| = 0.661, p < 0.001, and |R| = 0.544, p <0.001, respectively). Using a cutoff value of 7.75, the sensitivity and specificity of PG I/II ratio for predicting H. pylori-negatives were 86.3 and 87.8%, respectively (area under the curve 0.930). CONCLUSIONS: In hemodialysis patients, infection rate with H. pylori was <20%, with lower rates in patients receiving hemodialysis for longer terms. A PG I/II ratio with a cutoff value of 7.75 may be useful for screening for H. pylori status.

Efficacy of the Kyoto Classification of Gastritis in Identifying Patients at High Risk for Gastric Cancer.

Objective The Kyoto gastritis classification categorizes the endoscopic characteristics of Helicobacter pylori (H. pylori) infection-associated gastritis and identifies patterns associated with a high risk of gastric cancer. We investigated its efficacy, comparing scores in patients with H. pylori-associated gastritis and with gastric cancer. Methods A total of 1,200 patients with H. pylori-positive gastritis alone (n=932), early-stage H. pylori-positive gastric cancer (n=189), and successfully treated H. pylori-negative cancer (n=79) were endoscopically graded according to the Kyoto gastritis classification for atrophy, intestinal metaplasia, fold hypertrophy, nodularity, and diffuse redness. Results The prevalence of O-II/O-III-type atrophy according to the Kimura-Takemoto classification in early-stage H. pylori-positive gastric cancer and successfully treated H. pylori-negative cancer groups was 45.1%, which was significantly higher than in subjects with gastritis alone (12.7%, p<0.001). Kyoto gastritis scores of atrophy and intestinal metaplasia in the H. pylori-positive cancer group were significantly higher than in subjects with gastritis alone (all p<0.001). No significant differences were noted in the rates of gastric fold hypertrophy or diffuse redness between the two groups. In a multivariate analysis, the risks for H. pylori-positive gastric cancer increased with intestinal metaplasia (odds ratio: 4.453, 95% confidence interval: 3.332-5.950, <0.001) and male sex (1.737, 1.102-2.739, p=0.017). Conclusion Making an appropriate diagnosis and detecting patients at high risk is crucial for achieving total eradication of gastric cancer. The scores of intestinal metaplasia and atrophy of the scoring system in the Kyoto gastritis classification may thus be useful for detecting these patients.

Influence of low-dose proton pump inhibitors administered concomitantly or separately on the anti-platelet function of clopidogrel.

Proton pump inhibitors (PPIs) at low doses can effectively prevent gastrointestinal bleeding due to aspirin and are widely used in Japan for gastroprotection in patients taking anti-platelet agents. We examined the influence of different PPIs at low doses administered concomitantly or separately on anti-platelet functions of clopidogrel. In 41 healthy Japanese volunteers with different CYP2C19 genotypes who took clopidogrel 75 mg in the morning alone, or with omeprazole 10 mg, esomeprazole 10 mg, lansoprazole 15 mg, or rabeprazole 10 mg, either concomitantly in the morning or separately in the evening, we measured the inhibition of platelet aggregation (IPA, %) using VerifyNow P2Y12 assay at 4 h after the last clopidogrel dose on Day 7 of each regimen. IPA by clopidogrel with rabeprazole administered at lunchtime, approximately 4 h after clopidogrel, was also measured. Mean IPAs in those concomitantly receiving omeprazole, esomeprazole, lansoprazole or rabeprazole (47.2 ± 21.1%, 43.2 ± 20.2%, 46.4 ± 18.8%, and 47.3 ± 19.2%, respectively) were significantly decreased compared with those receiving clopidogrel alone (56.0%) (all ps < 0.001). This decrease was observed when PPIs were administered separately in the evening. However, IPA by clopidogrel with rabeprazole administered at lunchtime was 51.6%, which was markedly similar to that of clopidogrel alone (p = 0.114). All tested PPIs reduce the efficacy of clopidogrel when administered concomitantly. Our preliminary data suggest that administration of rabeprazole 4 h following clopidogrel may minimize potential drug-drug interactions.

Four-times-daily Dosing of Rabeprazole with Sitafloxacin, High-Dose Amoxicillin, or Both for Metronidazole-Resistant Infection with Helicobacter pylori in Japan.

BACKGROUND: The bacterial resistance of Helicobacter pylori to antimicrobial agents such as clarithromycin and metronidazole has been increasing worldwide, leading to the failure of eradication treatment. Here, we present an eradication regimen consisting of four-times-daily dosing (q.i.d.) of rabeprazole with potent acid inhibition. AIM: To investigate the efficacy of eradication therapy with rabeprazole q.i.d. and amoxicillin or sitafloxacin in Japanese infected with a metronidazole-resistant strain. METHODS: We retrospectively investigated the efficacy of eradication regimens with rabeprazole q.i.d. for 7 days in 111 Japanese pooled patients infected with a metronidazole-resistant strain of H. pylori at Hamamatsu University School of Medicine Hospital or the Shiga University of Medical Science Hospital: 1, with sitafloxacin 100 mg twice daily (b.i.d.) (n = 82); 2, with amoxicillin 500 mg q.i.d. (n = 15); and 3, with amoxicillin q.i.d. and sitafloxacin b.i.d.-combined regimen (n = 14). Eradication status was assessed at 8 weeks via a 13 C-urea breath test. RESULTS: Eradication rate on intention-to-treat analysis was 93.7% (95% confidence interval: 87.4-97.4%, 104/111), irrespective of the high prevalence of strains resistant to clarithromycin (81.1%, 90/111) and levofloxacin (42.3%, 47/111). No significant differences in eradication rates were observed among the different treatment regimens (p = .408), eradication history (p = .096) and different CYP2C19 genotypes (p = .789). On multivariate analysis, no significant risk factor for eradication failure by therapy with potent acid inhibition was seen. CONCLUSION: In Japanese patients infected with metronidazole-resistant strains of H. pylori, eradication rates exceeding 90% can be achieved using appropriate dosing of antibiotic agents with strain susceptibility (amoxicillin q.i.d. and/or sitafloxacin b.i.d.) together with acid inhibition for a full 24 h and rabeprazole 10 mg q.i.d. These findings may be further evidence for dual therapy with rabeprazole q.i.d. and an antibiotic agent (amoxicillin q.i.d. or sitafloxacin b.i.d.) in Japanese patients with metronidazole-resistant strains.

Severity of Gastric Mucosal Atrophy Is the Major Determinant of Plasma Ghrelin Level in Hemodialysis Patients.

BACKGROUND: Ghrelin, an orexigenic hormone, has multiple favorable functions including protein anabolism enhancement, anti-inflammatory actions, and cardiovascular protection. A low plasma ghrelin level is associated with increased mortality in patients treated with hemodialysis (HD). However, it is unclear whether the plasma ghrelin level in HD patients correlates with the severity of gastric mucosal atrophy and Helicobacter pylori status. METHODS: Seventy-eight maintenance HD patients and 51 non-dialysis patients with chronic kidney disease were evaluated for severity of gastric mucosal atrophy by gastroduodenoscopy and for H. pylori status using an anti-H. pylori-antibody and rapid urease test. Plasma acyl and des-acyl ghrelin levels were measured and their associations with relevant clinical parameters were investigated. RESULTS: Des-acyl ghrelin level in HD patients was significantly higher than that in patients with kidney function preserved. Although acyl and des-acyl ghrelin levels were similar between current H. pylori positive and negative HD patients, both levels decreased significantly with the progress of endoscopic gastric mucosal atrophy in HD patients. Serum pepsinogen (PG) I level and PG I/II ratio decreased significantly according to the severity of atrophy in HD patients and positively significantly correlated with both ghrelin levels. Multiple regression analysis showed significant positive correlations between acyl ghrelin and PG I levels (ß = 0.738, p < 0.001) and significant negative correlations between ghrelin and age, albumin, and creatinine levels. CONCLUSIONS: Gastric atrophy is the major determinant of ghrelin level in HD patients. Management practices, such as H. pylori eradication, before advanced atrophy may be required to prevent the decrease of ghrelin levels and improve the prognosis of HD patients.

Gastroesophageal Reflux Disease in Time Covering Eradication for All Patients Infected with Helicobacter pylori in Japan.

BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) has increased in Japan since the end of the 20th century due to changes in environmental factors, such as a decreased infection rate of Helicobacter pylori and increased ability of acid secretion in the Japanese population. In 2013, the Japanese health insurance system started to cover eradication treatment for all patients infected with H. pylori to prevent gastric cancer, suggesting we may soon be able to completely eradicate this infection in Japan. Re-clarification of the clinical characteristics of GERD in Japan is therefore required in time covering the eradication for all patients infected with H. pylori. SUMMARY: In Japan, more than half of GERD patients exhibit non-erosive reflux disease, and a majority of erosive esophagitis (RE) cases have mild severity of GERD (Los Angeles classification of grades A and B). The prevalence of RE in H. pylori-positive patients is relatively low (4.1%) compared to the general Japanese population (7.6-10.6%). In multivariate analysis to evaluate a risk of RE development, a risk in H. pylori-positive patients is elevated in those with mild gastric mucosal atrophy (C-I and C-II according to the Kimura-Takemoto classification, OR 12.14, 95% CI 1.28-115.26, p = 0.03) or with hiatal hernia (OR 5.24, 95% CI 1.80-15.22, p < 0.01). Here, we provide a comprehensive review of GERD in Japan, including associations between GERD and H. pylori infection, low-dose-aspirin-induced GERD, and pharmacological treatment for GERD. KEY MESSAGES: The recent decrease in the rate of H. pylori infection and increase in the proportion of elderly persons might have increased the prevalence of GERD in Japan.

Relationship between ghrelin, Helicobacter pylori and gastric mucosal atrophy in hemodialysis patients.

AIM: To investigate the relationship between plasma ghrelin level, Helicobacter pylori (H. pylori) infection status and the severity of atrophy in hemodialysis patients. METHODS: One hundred eights patients who received hemodialysis and 13 non-hemodialysis H. pylori-negative controls underwent gastroduodenoscopy to evaluate the severity of gastric atrophy. Serum levels of pepsinogen (PG) were measured as serum markers of gastric atrophy. H. pylori infection was evaluated by anti-H. pylori IgG antibody, rapid urease test and culture test. We classified H. pylori infection status as non-infection, present infection and past infection. In addition, plasma acyl-ghrelin and desacyl-ghrelin levels were measured by enzyme-linked immunosorbent assay. RESULTS: Infection rate of H. pylori was 45.4% (49/108). Acyl-ghrelin level in the non-infection group (39.4 ± 23.0 fmol/mL) was significantly higher than in the past (23.4 ± 19.9 fmol/mL, P = 0.005) and present infection groups (19.5 ± 14.0 fmol/mL, P < 0.001). Furthermore, desacyl-ghrelin level in the non-infection group (353.2 ± 190.2 fmol/mL) was significantly higher than those in the past (234.9 ± 137.5 fmol/mL, P = 0.008) and present infection groups (211.8 ± 124.2 fmol/mL, P < 0.001). Acyl-ghrelin was positively correlated with the PG I level and PG I/II ratio (|R| = 0.484, P < 0.001 and |R| = 0.403, P < 0.001, respectively). Both ghrelins were significantly decreased in accordance with the progress of endoscopic atrophy (both P < 0.001) and acyl-ghrelin was significantly lower in patients with mild, moderate and severe atrophy (24.5 ± 23.1 fmol/mL, 20.2 ± 14.9 fmol/mL and 18.3 ± 11.8 fmol/mL) than in those with non-atrophy (39.4 ± 22.2 fmol/mL, P = 0.039, P = 0.002 and P < 0.001, respectively). CONCLUSION: In hemodialysis patients, plasma ghrelin level was associated with the endoscopic and serological severity of atrophy related to H. pylori infection.

Prostate stem cell antigen gene TT genotype and development of intestinal metaplasia in Helicobacter pylori infection.

OBJECTIVES: Gastric cancer is etiologically related to interactions between Helicobacter pylori (H. pylori) infection, environmental and host factors. Gastric carcinoma is associated with a cascade of increasing atrophic gastric mucosal damage. Prostate stem cell antigen (PSCA) polymorphisms have been associated with an increased risk of gastric cancer. We aimed to examine the interaction between PSCA polymorphisms and H. pylori in the progression of H. pylori-related gastritis. METHODS: The genotypes (TT, TC and CC) of PSCA single nucleotide polymorphism rs2294008 among H. pylori infected and uninfected Bhutanese were compared with the severity of H. pylori-related gastritis [neutrophils, monocytes, atrophy scores, H. pylori density, and the presence and extent of intestinal metaplasia (IM)] using the updated Sydney system. RESULTS: Biopsies from 339 participants were included. The proportion of biopsies with IM was significantly (P < 0.05) greater in those with the TT genotype than in either those with the CT or CC genotype. Although no significant differences were found in inflammation or H. pylori density scores, the scores for IM at both gastric corpus and antrum among participants infected by H. pylori with the TT genotype was significantly (P < 0.05) greater than in the C allele carriers. CONCLUSION: PSCA TT genotype is associated with a more than a threefold increase in the prevalence and the extent of gastric mucosal IM compared to C allele carriers among H. pylori-infected Bhutanese.

Rapid metabolizer genotype of CYP2C19 is a risk factor of being refractory to proton pump inhibitor therapy for reflux esophagitis.

BACKGROUND: Proton pump inhibitors (PPIs) are mainly metabolized by cytochrome P450 2C19 (CYP2C19) and used as the first-line therapy for gastroesophageal reflux disease (GERD). However, while several studies have examined the influence of CYP2C19 polymorphism on GERD treatment with PPIs, most have had small sample sizes and were conducted in a single center. Here, we used meta-analysis to investigate whether or not the CYP2C19 rapid metabolizer (RM) genotype is a risk factor for GERD patients being refractory to PPI therapy. METHODS: PubMed and other electronic databases were systematically searched up to August 2014 using the following terms: "GERD and CYP2C19", "esophagitis and CYP2C19", and "non-erosive reflux disease and CYP2C19." Searches were limited to publications in English, and two investigators evaluated eligible studies and extracted data. RESULTS: The total efficacy rate of PPIs for GERD, including reflux esophagitis (RE) and non-erosive reflux disease, was 56.4% (95% confidence interval [CI]; 53.9-58.9%, 870/1543) in intention-to-treat analysis and 63.8% (95%CI; 61.3-66.2%, 950/1489) in per-protocol analysis. Efficacy rates varied significantly between CYP2C19 genotypes (intention-to-treat analysis: RMs, 52.2% [315/604]; intermediate metabolizers, 56.7% [298/526]; poor metabolizers [PMs], 61.3% [138/225]; P = 0.047). Among RE patients, CYP2C19 RMs had an increased risk of being refractory to PPI therapy compared with PMs (odds ratio: 1.661, 95% CI: 1.023-2.659, P = 0.040). CONCLUSIONS: The present meta-analysis demonstrates that CYP2C19 RMs with RE have an increased risk of being refractory to PPI therapy compared with PMs. Individualized dosing regimen with PPIs based on CYP2C19 genotype might be a valid therapeutic strategy for overcoming insufficient gastric acid inhibition.

Improvement of gastroesophageal reflux disease in Japanese patients with spinal kyphotic deformity who underwent surgical spinal correction.

BACKGROUND AND AIM: Spinal kyphotic deformity occasionally results in gastroesophageal reflux disease (GERD). The effects of acid reflux on the esophagus in kyphotic patients are unclear, however, and it is unknown whether acid reflux, endoscopic GERD, and reflux-related symptoms improve following surgical spinal correction in these patients. Herein, we investigated the characteristics of GERD in kyphotic patients and the improvement in GERD following surgical correction. METHODS: In 48 patients with severe kyphotic deformity scheduled for surgical spinal correction, we conducted esophagogastroduodenoscopy, 24-h pH monitoring and three questionnaire surveys, including the frequency scale for the symptoms of GERD (FSSG). We repeated these measurements after surgical correction and compared pre- and post-surgery values. RESULTS: Of 48 patients, 70.8% [95% CI: 55.9-83.0%, 34/48] had endoscopically evaluated esophageal mucosal injury. Regarding pH before surgery, 64.9% (CI: 47.5-79.8%, 24/37) had abnormal acid reflux (intraesophageal pH < 4 more than 5% of the time). FSSG score was significantly associated with the severity of GERD, and the positive rate was 52.6% (CI: 35.8-69.0%, 20/38). Following surgical correction, esophageal mucosal injury improved endoscopically in 90% of patients, and median total FSSG score significantly decreased from 8 (0-30) to 5 (0-19) (P = 0.005). Regarding pH after surgery, prevalence of abnormal acid reflux decreased from 66.7% (95% CI: 41.0-86.7%) to 33.3% (95% CI: 13.3-59.0%) (P = 0.045). CONCLUSION: Surgical spinal correction in kyphosis patients improves not only kyphotic deformity-related disorders but also esophageal mucosal injury, abnormal acid reflux, and reflux-related symptoms.

Factors associated with healing of artificial ulcer after endoscopic submucosal dissection with reference to Helicobacter pylori infection, CYP2C19 genotype, and tumor location: Multicenter randomized trial.

BACKGROUND AND AIM: Healing speed of peptic ulcer is affected by a number of factors, including Helicobacter pylori (H. pylori) infection and intragastric pH. Acid inhibition exerted by proton pump inhibitors differs by CYP2C19 genotype. Herein, we investigated whether healing speed of artificial ulcers formed after endoscopic submucosal dissection (ESD) was influenced by H. pylori infection, CYP2C19 genotype, or other factors. METHODS: A total of 96 H. pylori-positive patients with gastric tumors scheduled for ESD were randomly assigned to receive eradication therapy for H. pylori before ESD (pre-ESD eradication) (n = 44) or after (post-ESD eradication) (n = 52). Patients received eradication therapy consisting of lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 200 mg twice daily for 1 week. After ESD, lansoprazole 30 mg was given once daily for 8 weeks. Ulcer size was endoscopically measured on the next day and at 4 and 8 weeks after ESD. RESULTS: Mean reduction rate of artificial ulcer area in the pre-ESD eradication group was 94.7% ± 5.5% at 4 weeks, which was similar to that in the post-ESD eradication group (94.7% ± 6.7%, P = 0.987), irrespective of CYP2C19 genotype. In multivariate analyses, location of gastric tumor (middle and upper, odds ratio: 4.05, 95% CI: 1.620-10.230, P = 0.003) was a factor for 97% reduction of artificial ulcer area at 4 weeks post-ESD, but CYP2C19 genotype and H. pylori infection were not. CONCLUSION: Healing speed of ESD-induced artificial ulcer was affected by tumor location, but not by time of H. pylori eradication, resected size, or CYP2C19 genotype.