A phase 3, multicenter, single-arm, open-label study to assess the safety, tolerability, and immunogenicity of a single dose of 13-valent pneumococcal conjugate vaccine in Japanese participants aged 6-64 years who are considered to be at increased risk of pneumococcal disease and who are naive to pneumococcal vaccines.

BACKGROUND: This open-label, single-arm, phase 3 study evaluated safety and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) in pneumococcal vaccine-naive Japanese individuals aged 6-64 years at increased risk of pneumococcal disease (PD). METHODS: Participants received 1 PCV13 dose. Reactogenicity events were recorded for 7 days (individuals aged 6- to 17-year-old) or 14 days (individuals aged 18 to 64 years old) postvaccination. Adverse events (AEs) were collected for 1 month postvaccination. Opsonophagocytic activity (OPA) and anticapsular immunoglobulin G (IgG) geometric mean concentrations (GMCs) were measured for vaccine serotypes before and 1 month postvaccination. Post hoc analyses compared immunogenicity in participants categorized as at-risk (immunocompetent but having chronic medical conditions associated with increased PD risk) or high-risk (immunocompromised due to diseases/conditions and/or medications). RESULTS: 206 participants aged 6- to 17-year-old (n = 53) and 18 to 64 years old (n = 153) completed the study. Reactogenicity events were generally mild to moderate in severity. AEs were reported in 16% (33/206) of participants; 1.0% (2/206) were severe. Six AEs were vaccine-related; most were associated with local reactions. No serious AEs occurred. Circulating antibody levels for all 13 serotypes increased postvaccination. OPA geometric mean fold rises (GMFRs) from prevaccination to 1 month postvaccination were 5.5-61.7; lower limits of the 2-sided, 95% CI were > 1 for all serotypes. IgG GMFRs were consistent with OPA analyses. In post hoc analyses, 55.8% (115/206) and 44.2% (91/206) of participants were categorized as at risk and at high risk of PD, respectively; OPA GMFRs from prevaccination to 1 month postvaccination were 3.9-635.1, with lower limits of the 2-sided 95% CIs > 1 for all 13 serotypes across these risk groups; IgG GMFRs were consistent with OPA analyses. CONCLUSIONS: PCV13 was well tolerated and immunogenic in Japanese individuals aged 6-64 years considered at increased risk of PD. Results were broadly comparable with past PCV13 studies in other Japanese and non-Japanese populations. Registration number: NCT03571607; JapicCTI-184024.

Relationship between Knee Osteoarthritis and Spinopelvic Sagittal Alignment in Volunteers over 50 Years of Age.

STUDY DESIGN: Large cohort study of volunteers. PURPOSE: The purpose of this study was to investigate the relationship between the severity of knee osteoarthritis, assessed using the Kellgren-Lawrence (KL) grading scale, and spinopelvic sagittal alignment in older adult volunteers. OVERVIEW OF LITERATURE: The relationship between spinopelvic alignment in the sagittal plane and knee osteoarthritis in the coronal plane is unclear. METHODS: Volunteers over 50 years of age underwent radiographic analysis. Radiographic parameters including pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), thoracic kyphosis, and sagittal vertical axis (SVA) were measured. The the three Scoliosis Research Society-Schwab sagittal modifiers (PT, SVA, PI-LL) were categorized and the KL grade was assessed. Differences in spinopelvic parameters and Oswestry Disability Index (ODI) scores among KL grades were evaluated. RESULTS: A total of 396 volunteers (160 men, 236 women; mean age, 74.4 years) were analyzed. PI-LL and PT in KL4 were significantly higher compared to that in the other KL grades. However, there were no significant group differences in SVA. In women, but not in men, higher frequencies of the worst modifier grade (++) were observed for PI-LL and PT in the KL3 and KL4 groups compared to those for the other KL grades. In women, the ODI score in KL4 was worse compared to that in the other KL grades. CONCLUSIONS: Individuals over 50 years of age with severe knee osteoarthritis had poor lumbo-pelvic sagittal alignment. Moreover, the progression severity of knee osteoarthritis had more impact onstronger relationship with lumbo-pelvic malalignment and disability-related low back pain in women than in men.

Correction to: Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication.

In the original publication of the article, the figure 3 was published with errors. The corrected figure 3 should appear as in this correction.

Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication.

BACKGROUND AND AIMS: Eradication of Helicobacter pylori reduces the risk of gastric cancer. In this study, we investigated the risk beyond 10 years after eradication of H. pylori. METHODS: We conducted a retrospective cohort study of 2737 patients who had yearly endoscopic follow-up after cure of H. pylori infection. For comparison of gastric cancer risk in the second decade of follow-up with that in the first decade, we calculated standardized incidence ratios (SIRs) by dividing the number of observed cases of gastric cancer in the second decade of follow-up by that of expected cases which was estimated using the incidence rate ratio of age in the first decade. RESULTS: During the follow-up for as long as 21.4 years (mean 7.1 years), gastric cancer developed in 68 patients (0.35% per year). The SIRs for diffuse-type gastric cancer was infinity (0 expected case and 4 observed cases) in patients with mild gastric mucosal atrophy and 10.9 (95% confidence interval 4.53-26.1) with moderate atrophy, whereas no significant increase of SIRs was observed in intestinal-type cancer regardless of the grade of baseline gastric atrophy or in diffuse-type cancer in patients with severe atrophy even though who had the highest risk. CONCLUSIONS: The longer the follow-up, the greater the risk of developing diffuse-type gastric cancer becomes in patients with mild-to-moderate gastric atrophy at baseline. Endoscopic surveillance should be continued beyond 10 years after cure of H. pylori irrespective of the severity of gastric atrophy.

Peppermint oil solution is useful as an antispasmodic drug for esophagogastroduodenoscopy, especially for elderly patients.

BACKGROUND: Although hyoscine butyl bromide (HB) and glucagon (GL) are often used as antispasmodic drugs during esophagogastroduodenoscopy (EGD), these agents may cause adverse effects. Recently, it was reported that peppermint oil solution (PO) was very effective and had few side effects. AIM: We clarified the efficacy and usefulness of PO as an antispasmodic during upper endoscopy, especially for elderly patients. METHODS: This study was a non-randomized prospective study. The antispasmodic score (1-5, where 5 represents no spasm) was defined according to the degree of spasms of the antrum and difficulty of biopsy. We compared the antispasmodic scores between non-elderly patients (younger than 70) and elderly patients (70 years old or older) according to the antispasmodic agent. RESULTS: A total of 8,269 (Group PO: HB: GL: NO (no antispasmodic) = 1,893: 6,063: 157: 156) EGD procedures were performed. There was no significant difference in the antispasmodic score between Group PO (mean score ± standard deviation: 4.025 ± 0.925) and Group HB (4.063 ± 0.887). Among the non-elderly patients, those in Group PO (n = 599, 3.923 ± 0.935) had a worse antispasmodic score than those in Group HB (n = 4,583, 4.062 ± 0.876, P < 0.001). However, among the elderly patients, those in Group PO (n = 1,294, 4.073 ± 0.917) had similar scores to those in Group HB (n = 1,480, 4.064 ± 0.921, P = 0.83), and significantly better scores than those in Group GL (n = 69, 3.797 ± 0.933, P < 0.05). CONCLUSION: Peppermint oil was useful as an antispasmodic during EGD, especially for elderly patients.

Reinfection rate of Helicobacter pylori after eradication treatment: a long-term prospective study in Japan.

BACKGROUND: We previously reported that the reinfection rate with Helicobacter pylori in Japan was low despite a high prevalence of infection. In the present study, we extended our previous work to more accurately determine the reinfection rate. METHODS: We enrolled 1625 patients (219 women and 1406 men, mean age 50.8 years) who had received H. pylori eradication therapy. After documentation of eradication, bacterial culture and urea breath test were carried out yearly. H. pylori strains were analyzed by using random amplification of polymorphic DNA fingerprinting. RESULTS: A total of 1609 patients were followed for up to 12.5 years (mean 4.7 years); H. pylori became re-positive in 26 patients. In 13 of the 26 patients, H. pylori became positive at the first-year follow up. Stored H. pylori isolates were available for analysis from ten of the 13 patients; four of the isolates were genetically different from the initial strain, but the other six were identical to the initial strain. In the other 13 patients, H. pylori became positive at later follow up (mean 4.8 years; range 1.8-8.0 years). In all of the four of these patients whose isolates could be analyzed, the H. pylori strains were different from the initial strain. Assuming that reinfection occurred in the four patients positive for different strains of H. pylori at the first-year follow up and in the 13 positive at later follow up, the reinfection rate was 0.22% per year. CONCLUSIONS: When probable recrudescence (H. pylori positivity with identical strains) was excluded, the reinfection rate of H. pylori in this Japanese population was very low, but we note that reinfection can occur over many years.

Large waist circumference is a risk factor for reflux esophagitis in Japanese males.

BACKGROUND/AIMS: The prevalence of reflux esophagitis, which might lead to development of Barrett's esophagus and esophageal adenocarcinoma, has been increasing. The aim of this study was to assess risk factors for reflux esophagitis. METHODS: We conducted a cross-sectional study of 1,495 Japanese subjects undergoing health checkups (822 males and 673 females; median age 50 years) at a tertiary care center. RESULTS: One hundred and twenty-seven subjects (8%) had reflux esophagitis and hiatal hernia was observed in 292 subjects (20%). Reflux esophagitis (13 vs. 3%) and hiatal hernia (28 vs. 9%) were more frequent in males than females. Significant differences in clinical backgrounds were observed between females and males. Multivariate logistic regression analyses revealed that hiatal hernia (OR 6.63, 95% CI 2.47-17.8; p = 0.0002) was associated with reflux esophagitis in females. In males, age (per 1-year increment: OR 0.96, 95% CI 0.94-0.99; p = 0.007), hiatal hernia (OR 3.16, 95% CI 2.05-4.87; p < 0.0001) and waist circumference (per 1-cm increase: OR 1.09, 95% CI 1.02-1.15; p = 0.006) were associated with reflux esophagitis. CONCLUSIONS: Abdominal obesity may be an important risk factor for reflux esophagitis in males compared with females.

A combination treatment of entecavir and early-phase corticosteroid in severe exacerbation of chronic hepatitis B.

Of patients with severe exacerbation of chronic hepatitis B accompanied by jaundice and coagulopathy, 20%-30% have a fatal outcome. In this report, we describe 2 cases of severe exacerbation of chronic hepatitis B with jaundice and coagulopathy who were successfully treated with a combination of entecavir and corticosteroid. In both cases, rapid reductions in serum hepatitis B virus (HBV)-DNA levels were observed, and corticosteroid was stopped after serum HBV-DNA levels became undetectable. Entecavir treatment was continued. Generally, entecavir treatment reduced serum HBV-DNA levels rapidly, although the improvement in liver function was delayed by a few weeks. During this time lag, liver cell injury continued and the disease progressed. Corticosteroid suppressed the excessive host immune response and was useful for stopping progressive deterioration. A combination of entecavir and early-phase corticosteroid may be a useful treatment in severe exacerbation of chronic hepatitis B.

Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells.

Peripheral blood (PB)-derived CD14+ monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)- or PB-derived CD34-/CD14+ cells are involved in reendothelialization after carotid balloon injury. Although neither hematopoietic nor mesenchymal stem cells were included in human BM-derived CD34-/CD14+ monocyte lineage cells (BM-MLCs), they expressed EC-specific markers (Tie2, CD31, VE-cadherin, and endoglin) to an extent identical to mature ECs. When BM-MLCs were cultured with vascular endothelial growth factors, hematopoietic markers were drastically decreased and new EC-specific markers (Flk and CD34) were induced. BM-MLCs were intra-arterially transplanted into balloon-injured arteries of athymic nude rats. When BM-MLCs were activated by monocyte chemoattractant protein-1 (MCP-1) in vivo or in vitro, they adhered onto injured endothelium, differentiated into EC-like cells by losing hematopoietic markers, and inhibited neointimal hyperplasia. Ability to prevent neointimal hyperplasia was more efficient than that of BM-derived CD34+ cells. MCP-dependent adhesion was not observed in PB-derived CD34-/CD14+ monocytes. Regenerated endothelium exhibited a cobblestone appearance, blocked extravasation of dye, and induced NO-dependent vasorelaxation. Basal adhesive activities on HUVECs under laminar flow and beta1-integrin expression (basal and active forms) were significantly increased in BM-MLCs compared with PB-derived monocytes. MCP-1 markedly enhanced adhesive activity of BM-MLCs (2.8-fold) on HUVECs by activating beta1-integrin conformation. Thus, BM-MLCs can function as EC progenitors that are more potent than CD34+ cells and acquire the ability to adhere on injured endothelium in a MCP-1-dependent manner, leading to reendothelialization associated with inhibition of intimal hyperplasia. This will open a novel window to MCP-1-mediated biological actions and vascular regeneration strategies by cell therapy.