Comparison of five-day Helicobacter pylori eradication regimens: rabeprazole-based and omeprazole-based regimens with and without omeprazole pretreatment

Background: The onset of antisecretory activity of rabeprazole is faster than that of omeprazole.Objective: This study was performed to compare the efficacy of short-term rabeprazole-based triple therapy with that of omeprazole-based triple therapy and to determine the influence of omeprazole pretreatment in omeprazole-based short-term triple therapy.Methods: This was a 2-center, open-label, prospective, randomized study. Patients who tested positive for Helicobacter (formerly Campylobacter) pylori were randomized to one of three 5-day regimens: (1) rabeprazole 20 mg BID, amoxicillin 500 mg TID, and clarithromycin 400 mg BID (RAC group); (2) omeprazole 20 mg BID, amoxicillin 500 mg TID, and clarithromycin 400 mg BID without omeprazole pretreatment (OAC1 group); and (3) omeprazole 20 mg BID, amoxicillin 500 mg TID, and clarithromycin 400 mg BID with 5 days of omeprazole pretreatment 20 mg BID (OAC2 group). Eradication was assessed by ¹³C-urea breath test and rapid urease test ∼1 month after completion of treatment. All patients who entered this study were included in the intent-to-treat (ITT) analysis, patients who completed the study were included in the per-protocol (PP) analysis, and patients who did not undergo the ¹³C-urea breath test and rapid urease test were included in the all-patients-treated (APT) analysis.Results: A total of 120 patients (86 men, 34 women; mean [SD] age, 55.8 [14.3] years; range, 19-86 years) were assigned to the RAC, OAC1, or OAC2 group (40 patients in each group). ITT, PP, and APT eradication rates in the RAC group were 90%, 92%, and 90%, respectively; in the OAC1 group, 75%, 83%, and 75%; and in the OAC2 group, 85%, 90%, and 87%. These eradication rates were not significantly different between groups.Conclusions: Eradication rates did not differ significantly between the three 5-day proton pump inhibitor-based triple therapies in this study population. However, 5-day rabeprazole-based triple therapy tends to be more effective than 5-day omeprazole-based triple therapy in the eradication of H pylori, and treatment with omeprazole before eradication therapy may improve the eradication rates of 5-day omeprazole-based therapy.     

Application of a shape memory alloy for internal artificial organs

Shape memory alloy (SMA) is an actuator with high efficiency, and for this reason, SMA is suitable for totally implantable artificial internal organs. We have thought about the various possible applications, and one is an artificial sphincter. Many patients with cancer have a stoma, with which control of excretion is, of course, difficult. It limits the quality of life (QOL) of patients with stomata. If there is a sphincter for the stoma, control becomes possible. Therefore, an artificial anal sphincter was developed. Energy will be supplied by the use of a transcutaneous energy transmission system (TETS). The energy is used to raise the temperature and this becomes the drive energy in the SMA. This system can achieve very high efficiency; therefore, this actuator may be suitable for artificial internal organs. This system is currently in the stage of animal experimentation. By opening and shutting an artificial anal sphincter, excretion becomes possible. Application of this totally implantable system to artificial myocardium is considered in this article. SMA thread was sewn together, and the artificial myocardium was applied to the outside of a heart. For improvement of the cooling time, Peltier elements were adopted in this artificial myocardium. By the use of Peltier elements, rapid cooling becomes possible. Using this artificial myocardium, cardiac contraction may be assisted. In this way, various applications of the SMA are being considered in Tohoku University.     

Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease

Background

Klotho is a single-pass transmembrane protein, which appears to be implicated in aging. The purpose of the present study was to characterize the relationship between the soluble Klotho level and renal function in patients with various degrees of chronic kidney disease (CKD).

Methods

The levels of soluble Klotho in the serum and urine obtained from one hundred thirty-one CKD patients were determined by a sandwich enzyme-linked immunosorbent assay system.

Results

The amount of urinary excreted Klotho during the 24 hr period ranged from 1.6 to 5178 ng/day (median 427 ng/day; interquartile range [IR] 56.8-1293.1), and the serum Klotho concentration ranged from 163.9 to 2123.7 pg/ml (median 759.7 pg/ml; IR 579.5-1069.1). The estimated glomerular filtration rate (eGFR) was significantly correlated with the log-transformed values of the amount of 24 hr urinary excreted Klotho (r?=?0.407, p?<?0.01) and the serum Klotho levels (r?=?0.232, p?<?0.01). However, a stepwise multiple regression analysis identified eGFR to be a variable independently associated only with the log-transformed value of the amount of 24-hr urinary excreted Klotho but not with the log-transformed serum Klotho concentration. Despite the strong correlation between random urine protein-to-creatinine ratio and the 24 hr urinary protein excretion (r?=?0.834, p?<?0.01), a moderate linear association was observed between the log-transformed value of the amount of 24 hr urinary excreted Klotho and that of the urinary Klotho-to-creatinine ratio (Klotho/Cr) in random urine specimens (r?=?0.726, p?<?0.01).

Conclusions

The amount of urinary Klotho, rather than the serum Klotho levels, should be linked to the magnitude of the functioning nephrons in CKD patients. The use of random urine Klotho/Cr as a surrogate for the amount of 24-hr urinary excreted Klotho needs to be evaluated more carefully.

     

The time course of flow-mediated vasodilation and endothelial dysfunction in patients with a cardiovascular risk factor

The relationship between having a cardiovascular risk factor and endothelial dysfunction observed on a time-course analysis of brachial artery flow-mediated vasodilation (FMD) remains unclear. We enrolled 257 patients who had at least one cardiovascular risk factor. We measured FMD magnitude of the percentage change in peak diameter (ΔFMD), maximum FMD rate calculated as the maximum slope of dilation (FMD-MDR), and integrated FMD response calculated as the area under the dilation curve during the 60- and 120-second dilation periods (FMD-AUC₆₀ and FMD-AUC₁₂₀) using a semiautomatic edge-detection algorithm. FMD-AUC₆₀ and FMD-AUC₁₂₀ were negatively correlated with the Framingham risk score (FMD-AUC₆₀: r = ?0.15, P = .023; FMD-AUC₁₂₀: r = ?0.17, P = .007), whereas this association was not found in the case of either the ΔFMD or the FMR-MDR. The Framingham risk score was significantly higher in patients in the lowest tertile for FMD-AUC₁₂₀ (FMD-AUC₁₂₀ <5.0 mm × second) than in those in the highest tertile for FMD-AUC₁₂₀ (FMD-AUC₁₂₀ ≥11.0 mm × second) (12.9 ± 8.7 vs. 8.6 ± 7.8%, P = .002). The lowest tertile for FMD-AUC₁₂₀ was independently associated with the Framingham risk score (β = 0.10, P = .011), after adjustments were made for age, gender, and smoking and drinking status. FMD-AUC₁₂₀ was associated with cardiovascular risk.     

Neonatal herpes simplex type II virus infection complicated with meningitis and virus-associated hemophagocytic syndrome

A 14-day-old neonate was transferred to our university hospital because of respiratory distress and mild disturbance of consciousness. He had no history of abnormal pregnancy or delivery, but had developed apnea at 6 days old. Thereafter, respiratory distress progressed and his condition deteriorated. On admission to our hospital, several vesicles were found on the left upper arm, and moderate hepatomegaly was also present. Herpes simplex virus (HSV) type II genome was detected from serum, spinal fluid, and bone marrow. Laboratory examinations revealed typical abnormalities of disseminated intravascular coagulation, increased levels of serum ferritin, aspartate aminotransferase, and lactate dehydrogenase. Bone marrow aspiration demonstrated activated macrophages and hemophagocytosis. Spinal tap revealed numerous mononuclear cells. Meningitis and virus-associated hemophagocytic syndrome (VAHS) due to systemic HSV type II infection were thus diagnosed. Acyclovir (60 mg/kg/day) and vidarabine were promptly administered. Dexamethasone palmitate and intravenous cyclosporine were also administered for systemic inflammation due to VAHS. Finally, these aggressive therapies rescued the patient without any sequelae. In general, neonatal systemic HSV infection is life-threatening and results in poor intact survival. Our case report suggests that not only antiviral treatment for HSV, but also anti-inflammatory treatment including steroid and cyclosporine should be considered from the early phase of neonatal systemic HSV infection.     

Teleost IL-6 promotes antibody production through STAT3 signaling via IL-6R and gp130

Teleost IL-6 is upregulated after antigen stimulation; therefore, we hypothesized that fish IL-6 contributes to antibody production during immune responses against infections. To verify this hypothesis, we first cloned IL-6R and gp130 in fugu (Takifugu rubripes) in the present study. The membrane and soluble forms of IL-6R were identified by the identification of cDNA clones of IL-6R homologues. Three STAT3-docking sites were found in the intracellular region of fugu gp130. Expression analysis showed that fugu IL-6R and gp130 were expressed in mIgM(+) B cells, suggesting that fugu B cells are stimulated by IL-6. Recombinant fugu IL-6 (rfIL-6) increased the gene expression of secretory antibodies by mIgM(+) B cells in vitro. The rfIL-6 and soluble form of rfIL-6R activated STAT3 phosphorylation in the B cells and a cultured cell line transfected with fugu gp130. These results indicate that fugu IL-6 enhances antibody production in the B-cell lineage via gp130 and STAT3 signaling.     

Two neonatal cholestasis patients with mutations in the SRD5B1 (AKR1D1) gene: diagnosis and bile acid profiles during chenodeoxycholic acid treatment

Background and aims

In two Japanese infants with neonatal cholestasis, 3-oxo-Δ⁴-steroid 5β-reductase deficiency was diagnosed based on mutations of the SRD5B1 gene. Unusual bile acids such as elevated 3-oxo-Δ⁴ bile acids were detected in their serum and urine by gas chromatography–mass spectrometry. We studied effects of oral chenodeoxycholic acid treatment.

Patients and methods

SRD5B1 gene analysis used peripheral lymphocyte genomic DNA. Diagnosis and treatment of these two patients were investigated retrospectively and prospectively investigated.

Results

With respect to SRD5B1, one patient was heterozygous (R266Q, a novel mutation) while the other was a compound heterozygote (G223E/R261C). Chenodeoxycholic acid treatment was effective in improving liver function and decreasing unusual bile acids such as 7α-hydroxy- and 7α,12α-dihydroxy-3-oxo-4-cholen-24-oic acids in serum and urine.

Conclusion

Primary bile acid treatment using chenodeoxycholic acid was effective for these patients treated in early infancy before the late stage of chronic cholestatic liver dysfunction.     

Guidance on the use of canakinumab in patients with cryopyrin-associated periodic syndrome in Japan

Cryopyrin-associated periodic syndrome (CAPS) is an orphan disease with incidence of about one in 1,000,000 persons. This autoinflammatory disease develops in the neonatal period or early childhood, with various inflammatory symptoms occurring repeatedly throughout the patient’s lifetime. It is caused by abnormality of the NLRP3 protein which mediates the intracellular signal transduction mechanism of inflammatory processes, resulting in continuous overproduction of interleukin (IL)-1β, which induces chronic inflammation and progressive tissue damage. Definitive diagnosis of CAPS is difficult, and treatment has also been difficult because of a lack of effective medications in Japan. Clinical studies of human anti-human IL-1β monoclonal antibody (canakinumab) treatment were conducted in Japan, and approval was granted for therapeutic use of canakinumab for CAPS in September 2011. Similar to other biological drugs, canakinumab is clinically highly effective. However, sufficient attention to the method of use and adverse drug reactions is necessary. This guidance describes the use of canakinumab in Japan for CAPS in relation to exclusion criteria, method of use, evaluation criteria, and adverse drug reactions.     

Prevalence and risk factors for lymph node metastasis after noncurative endoscopic resection for early gastric cancer: a systematic review and meta-analysis

Background

Additional surgery for all patients with noncurative resection after endoscopic resection (ER) for early gastric cancer (EGC) may be excessive due to the relatively low rate of lymph node metastasis (LNM) in such patients. However, the prevalence and risk factors for LNM after noncurative ER have not been consistent across studies.

Methods

We performed a systematic review of electronic databases through August 10, 2018 to identify cohort studies with patients who underwent additional surgery after noncurative ER for EGC. The prevalence of LNM in such patients was extracted for all studies. Odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of LNM, when possible.

Results

We identified 24 studies comprising 3877 patients with 311 having LNM (pooled prevalence, 8.1%). The risk of LNM was significantly increased in lymphatic invasion (OR [95% confidence interval] = 4.22 [2.88–6.19]), lymphovascular invasion (LVI) (4.17 [2.90–5.99]), vascular invasion (2.38 [1.65–3.44]), positive vertical margin (2.16 [1.59–2.93]), submucosal invasion depth of ≥ 500 μm (2.14 [1.48–3.09]), and tumor size > 30 mm (1.77 [1.31–2.40]). In contrast, there was no significant association between undifferentiated-type or ulceration (scar) and LNM. When studies were restricted to those that evaluated the adjusted OR, the risk of vascular invasion for LNM did not reach statistical significance.

Conclusions

Several pathological factors, most notably lymphatic invasion and LVI, were associated with LNM in patients with noncurative resection after ER for EGC. Lymphatic and vascular invasion should be assessed separately instead of LVI (PROSPERO CRD42018109996).