Comparison of metronidazole versus clarithromycin in first-line vonoprazan-based triple therapy for Helicobacter pylori: A multicenter randomized trial in Japan.

Background and Aim: To date, no randomized trials have compared the efficacy of 7-day vonoprazan, amoxicillin, and metronidazole triple therapy (VAM) versus 7-day vonoprazan, amoxicillin, and clarithromycin triple therapy (VAC) as a first-line treatment for Helicobacter pylori eradication. This study was performed to compare the efficacy of VAM and VAC as first-line treatments. Methods: This prospective multicenter randomized trial was performed in Japan and involved 124 H. pylori-positive patients without a history of eradication. Patients without antibiotic resistance testing of H. pylori were eligible. The patients were randomized to receive either VAC (vonoprazan 20 mg + amoxicillin 750 mg + clarithromycin 200 or 400 mg twice a day) or VAM (vonoprazan 20 mg + amoxicillin 750 mg + metronidazole 250 mg twice a day) for 7 days, with stratification by age and sex. Eradication success was evaluated using the 13C-urea breath test. We evaluated safety using patient questionnaires (UMIN000025773). Results: The intention-to-treat and per-protocol eradication rates of VAM were 91.3% (95% confidence interval [CI], 82.0-96.7%) and 92.6% (95% CI, 83.7-97.6%), respectively, and those of VAC were 89.1% (95% CI, 77.8-95.9%) and 96.1% (95% CI, 86.5-99.5%), respectively. No significant difference was observed between VAM and VAC in either analysis (P = 0.76 and P = 0.70, respectively). Abdominal fullness was more frequent in patients who received VAM than VAC. Conclusions: These findings suggest that VAM as a first-line treatment in Japan can be categorized as grade B (intention-to-treat cure rate of 90-95%) and have potential as a first-line national insurance -approved regimen.

Prospective Study of Vonoprazan-Based First-Line Triple Therapy with Amoxicillin and Metronidazole for Clarithromycin-Resistant Helicobacter pylori.

AIM: This was a prospective, multicenter, single-arm intervention, against historical controls, study of the efficacy of a vonoprazan-based 7-day triple regimen with metronidazole (VPZ-AMPC-MNZ) as a first-line therapy for eradicating clarithromycin-resistant Helicobacter pylori (H. pylori). METHODS: We enrolled 35 patients positive for clarithromycin-resistant H. pylori, as assessed by culture, without a history of eradication. These 35 patients were prospectively eradicated with VPZ-AMPC-MNZ. As historical controls, we also assessed 98 patients with clarithromycin-resistant H. pylori from our prior prospective studies, who achieved H. pylori eradication with a 7-day triple regimen including clarithromycin (VPZ-AMPC-CAM). A preplanned analysis was performed as a superiority study against the historical controls (VPZ-AMPC-MNZ compared to VPZ-AMPC-CAM). In each regimen, vonoprazan was used at 20 mg bid, amoxicillin at 750 mg bid, metronidazole at 250 mg bid, and clarithromycin at 200 mg or 400 mg bid for 7 days. We assessed the outcome of eradication therapy using a 13C-urea breath test or H. pylori stool antigen test. We evaluated safety using patient questionnaires. RESULTS: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of VPZ-AMPC-MNZ were both 100% (95% confidence interval (95% CI) 90.0-100%, n = 35). The eradication rates of VPZ-AMPC-CAM were 76.5% (95% CI 66.9-84.5%, n = 98) in the ITT analysis and 77.3% (95% CI 67.7-85.2%, n = 97) in the PP analysis. The eradication rate of VPZ-AMPC-MNZ was significantly higher than that of VPZ-AMPC-CAM in both the ITT (p = 0.00052) and PP (p = 0.00095) analyses. CONCLUSIONS: The findings suggest that 7-day VPZ-AMPC-MNZ was superior to 7-day VPZ-AMPC-CAM as a first-line regimen for eradicating clarithromycin-resistant H. pylori. We suggest VPZ-AMPC-MNZ as the standard first-line regimen for eradication of clarithromycin-resistant H. pylori in Japan.

The Origin of Epithelium with Low-Grade Atypia in Early Gastric Cancer.

INTRODUCTION: Helicobacter pylori (HP) infection causes chronic inflammation and atrophy of the gastric mucosa and thus a high risk of gastric cancer (GC). With the increasing success of HP infection treatment, a larger number of GCs that develop after eradication can be assessed. Several studies have shown that epithelium with low-grade atypia (ELA) is a frequent characteristic of these GCs, but the origin of this condition is unknown. In this study, we compared the mucin phenotype, cellular proliferation, and p53 staining in ELA and cancerous tissues obtained from patients with GC with and without HP eradication. METHODS: The study population consisted of 23 patients with GC that developed after successful HP eradication therapy (eradicated group) and 24 patients with GC and HP infection (infected group). The prevalence of ELA was determined by hematoxylin and eosin staining. Tumor tissue and ELA samples were further analyzed by immunohistochemical staining for Muc5AC, Muc2, p53, and Ki-67. RESULTS: The ELA coverage rate was significantly higher in the eradicated group than in the infected group. Gastric-type mucin was frequently expressed by the ELA, and the mucin phenotypes of ELA and cancerous areas differed in 75% of cases. The Ki-67 labeling index was consistently lower in ELA than in the cancerous mucosa. Fourteen of 21 (66.7%) cancerous lesions, but only 3 ELA samples, were p53-positive. CONCLUSION: In most cases, ELA on the surfaces of GCs seems to have originated from normal gastric cells, not from cancer cells.

Canine sexual dimorphism in Ardipithecus ramidus was nearly human-like.

Body and canine size dimorphism in fossils inform sociobehavioral hypotheses on human evolution and have been of interest since Darwin's famous reflections on the subject. Here, we assemble a large dataset of fossil canines of the human clade, including all available Ardipithecus ramidus fossils recovered from the Middle Awash and Gona research areas in Ethiopia, and systematically examine canine dimorphism through evolutionary time. In particular, we apply a Bayesian probabilistic method that reduces bias when estimating weak and moderate levels of dimorphism. Our results show that Ar. ramidus canine dimorphism was significantly weaker than in the bonobo, the least dimorphic and behaviorally least aggressive among extant great apes. Average male-to-female size ratios of the canine in Ar. ramidus are estimated as 1.06 and 1.13 in the upper and lower canines, respectively, within modern human population ranges of variation. The slightly greater magnitude of canine size dimorphism in the lower than in the upper canines of Ar. ramidus appears to be shared with early Australopithecus, suggesting that male canine reduction was initially more advanced in the behaviorally important upper canine. The available fossil evidence suggests a drastic size reduction of the male canine prior to Ar. ramidus and the earliest known members of the human clade, with little change in canine dimorphism levels thereafter. This evolutionary pattern indicates a profound behavioral shift associated with comparatively weak levels of male aggression early in human evolution, a pattern that was subsequently shared by Australopithecus and Homo.

Estimating sexual size dimorphism in fossil species from posterior probability densities.

Accurate characterization of sexual dimorphism is crucial in evolutionary biology because of its significance in understanding present and past adaptations involving reproductive and resource use strategies of species. However, inferring dimorphism in fossil assemblages is difficult, particularly with relatively low dimorphism. Commonly used methods of estimating dimorphism levels in fossils include the mean method, the binomial dimorphism index, and the coefficient of variation method. These methods have been reported to overestimate low levels of dimorphism, which is problematic when investigating issues such as canine size dimorphism in primates and its relation to reproductive strategies. Here, we introduce the posterior density peak (pdPeak) method that utilizes the Bayesian inference to provide posterior probability densities of dimorphism levels and within-sex variance. The highest posterior density point is termed the pdPeak. We investigated performance of the pdPeak method and made comparisons with the above-mentioned conventional methods via 1) computer-generated samples simulating a range of conditions and 2) application to canine crown-diameter datasets of extant known-sex anthropoids. Results showed that the pdPeak method is capable of unbiased estimates in a broader range of dimorphism levels than the other methods and uniquely provides reliable interval estimates. Although attention is required to its underestimation tendency when some of the distributional assumptions are violated, we demonstrate that the pdPeak method enables a more accurate dimorphism estimate at lower dimorphism levels than previously possible, which is important to illuminating human evolution.

Helicobacter pylori rescue treatment with vonoprazan, metronidazole, and sitafloxacin in the presence of penicillin allergy.

BACKGROUND AND AIM: To assess the efficacy and safety of 7-day Helicobacter pylori rescue treatment consisting of a vonoprazan (VPZ), metronidazole (MNZ), and sitafloxacin (STFX) regimen (VPZ-MNZ-STFX therapy) in patients with penicillin allergy. METHODS: This was a registered prospective intervention study. Patients with penicillin allergy who were diagnosed with H. pylori infection and had a history of H. pylori eradication were eligible for inclusion. Seventeen patients were prospectively treated with VPZ 20 mg bid, MNZ 250 mg bid, and STFX 100 mg bid for 7 days. Safety was evaluated using a questionnaire on adverse effects. RESULTS: The eradication rate of 7-day VPZ-MNZ-SFTX therapy was 88.2% (95% confidence interval: 63.6-98.5%; n = 17) in both intention-to-treat and per-protocol analyses. On the questionnaire, 25% of patients reported experiencing diarrhea, with a score of 2 or 3. All patients undergoing VPZ-MNZ-STFX therapy completed 100% of their medication course. CONCLUSION: Rescue H. pylori eradication with VPZ-MNZ-STFX therapy is effective and well tolerated in patients with penicillin allergy (UMIN000016335, jRCTs031180133).

NAFLD exacerbates cholangitis and promotes cholangiocellular carcinoma in mice.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition, affecting up to 25% of the population worldwide. NAFLD has been linked to several conditions, including hepatic inflammation, fibrosis, and hepatocellular carcinoma (HCC), however the role of NAFLD in cholangitis and the development of cholangiocellular carcinoma (CCC) remains poorly understood. This study investigated whether a high-fat diet (HFD) promotes cholangitis and the development of CCC in mice. We used liver-specific E-cadherin gene (CDH1) knockout mice, CDH1∆Liv , which develop spontaneous inflammation in the portal areas along with periductal onion skin-like fibrosis, similar to that of primary sclerosing cholangitis (PSC). An HFD or normal diet (ND) was fed to CDH1∆Liv mice for 7 mo. In addition, CDH1∆Liv mice were crossed with LSL-KrasG12D mice, fed an HFD, and assessed in terms of liver tumor development. The extent of cholangitis and number of bile ductules significantly increased in mice fed an HFD compared with ND-administered CDH1∆Liv mice. The numbers of Sox9 and CD44-positive stem cell-like cells were significantly increased in HFD mice. LSL-KrasG12D /CDH1∆Liv HFD mice exhibited increased aggressiveness along with the development of numerous HCC and CCC, whereas LSL-KrasG12D /CDH1∆Liv ND mice showed several macroscopic tumors with both HCC and CCC components. In conclusion, NAFLD exacerbates cholangitis and promotes the development of both HCC and CCC in mice.

A 1.4-million-year-old bone handaxe from Konso, Ethiopia, shows advanced tool technology in the early Acheulean.

In the past decade, the early Acheulean before 1 Mya has been a focus of active research. Acheulean lithic assemblages have been shown to extend back to ∼1.75 Mya, and considerable advances in core reduction technologies are seen by 1.5 to 1.4 Mya. Here we report a bifacially flaked bone fragment (maximum dimension ∼13 cm) of a hippopotamus femur from the ∼1.4 Mya sediments of the Konso Formation in southern Ethiopia. The large number of flake scars and their distribution pattern, together with the high frequency of cone fractures, indicate anthropogenic flaking into handaxe-like form. Use-wear analyses show quasi-continuous alternate microflake scars, wear polish, edge rounding, and striae patches along an ∼5-cm-long edge toward the handaxe tip. The striae run predominantly oblique to the edge, with some perpendicular, on both the cortical and inner faces. The combined evidence is consistent with the use of this bone artifact in longitudinal motions, such as in cutting and/or sawing. This bone handaxe is the oldest known extensively flaked example from the Early Pleistocene. Despite scarcity of well-shaped bone tools, its presence at Konso shows that sophisticated flaking was practiced by ∼1.4 Mya, not only on a range of lithic materials, but also occasionally on bone, thus expanding the documented technological repertoire of African Early Pleistocene Homo.

Variation of bony labyrinthine morphology in Mio-Plio-Pleistocene and modern anthropoids.

OBJECTIVES: The bony labyrinth of the inner ear has special relevance when tracking phenotypic evolution because it is often well preserved in fossil and modern primates. Here we track the evolution of the bony labyrinth of anthropoid primates during the Mio-Plio-Pleistocene-the time period that gave rise to the extant great apes and humans. MATERIALS AND METHODS: We use geometric morphometrics to analyze labyrinthine morphology in a wide range of extant and fossil anthropoids, including New World and Old World monkeys, apes, and humans; fossil taxa are represented by Aegyptopithecus, Microcolobus, Epipliopithecus, Nacholapithecus, Oreopithecus, Ardipithecus, Australopithecus, and Homo. RESULTS: Our results show that the morphology of the anthropoid bony labyrinth conveys a statistically significant phylogenetic signal especially at the family level. The bony labyrinthine morphology of anthropoids is also in part associated with size, but does not cluster by locomotor adaptations. The Miocene apes examined here, regardless of inferred locomotor behaviors, show labyrinthine morphologies distinct from modern great apes. DISCUSSION: Our results suggest that labyrinthine variation contains mixed signals and alternative explanations need to be explored, such as random genetic drift and neutral phenotypic evolution, as well as developmental constraints. The observed pattern in fossil and extant hominoids also suggests that an additional factor, for example, prenatal brain development, could have potentially had a larger role in the evolutionary modification of the bony labyrinth than hitherto recognized.

Consistency of Trans-Abdominal and Water-Immersion Ultrasound Images of Diseased Intestinal Segments in Crohn's Disease.

The aim of this study is to clarify whether trans-abdominal ultrasound (TAUS) can reflect actual intestinal conditions in Crohn's disease (CD) as effectively as water-immersion ultrasound (WIUS) does. This retrospective study enrolled 29 CD patients with 113 intestinal lesions. Five ultrasound (US) parameters (distinct presence/indistinct presence/disappearance of wall stratification in the submucosal and mucosal layers; thickened submucosal layer; irregular mucosal surface; increased fat wrapping around the bowel wall; and fistula signs) that may indicate different states in CD were determined by TAUS and WIUS for the same lesion. Using WIUS as a reference standard, the sensitivity, specificity, and accuracy of TAUS were calculated. The degree of agreement between TAUS and WIUS was evaluated by the kappa coefficient. All US parameters of TAUS had an accuracy >70% (72.6-92.7%). The highest efficacy of TAUS was obtained for fistula signs (sensitivity, specificity, and accuracy values were 63.6%, 96.0%, and 92.7%, respectively). All US parameters between TAUS and WIUS had a definitive (p ≤ 0.001) and moderate-to-substantial consistency (kappa value = 0.446-0.615). The images of TAUS showed substantial similarity to those of WIUS, suggesting that TAUS may function as a substitute to evaluate the actual intestinal conditions of CD.

Loss of Pancreatic E-Cadherin Causes Pancreatitis-Like Changes and Contributes to Carcinogenesis.

BACKGROUND & AIMS: E-cadherin (Cdh1) is a key molecule for adherence required for maintenance of structural homeostasis. Loss of E-cadherin leads to poor prognosis and the development of resistance to chemotherapy in pancreatic cancer. Here, we evaluated the physiological and pathologic roles of E-cadherin in the pancreas. METHODS: We crossbred Ptf1a-Cre mice with Cdh1f/f mice to examine the physiological roles of E-cadherin in the pancreas. In addition, we crossbred these mice with LSL-KrasG12D/+ mice (PKC) to investigate the pathologic roles of E-cadherin. We also generated a tamoxifen-inducible system (Ptf1a-CreERT model). Organoids derived from these models using lentiviral transduction were analyzed for immunohistochemical features. Established cell lines from these organoids were analyzed for migratory and invasive activities as well as gene expression by complementary DNA microarray analyses. RESULTS: None of the Ptf1a-Cre mice crossbred with Cdh1f/f mice survived for more than 28 days. We observed aberrant epithelial tubules that resembled the structure of acinar-to-ductal metaplasia after postnatal day 6, showing features of pancreatitis. All of the PKC mice died within 10 days. We observed tumorigenicity with increasing stroma-like aggressive tumors. Ptf1a-CreERT models showed that deletion of E-cadherin led to earlier pancreatic intraepithelial neoplasm formation. Cells established from PKC organoids had greater migratory and invasive activities, and these allograft tumors showed a poorly differentiated phenotype. Gene expression analysis indicated that Hdac1 was up-regulated in PKC cell lines and a histone deacetylase 1 inhibitor suppressed PKC cell proliferation. CONCLUSIONS: Under physiological conditions, E-cadherin is important for maintaining the tissue homeostasis of the pancreas. Under pathologic conditions with mutational Kras activation, E-cadherin plays an important role in tumor formation via the acquisition of tumorigenic activity.

[A Case of Mucosal Gastric Cancer with Lymph Node Metastasis Successfully Treated with Chemotherapy].

A 64-year-old man was found to have an irregular region in the stomach by medical examinations. Upper gastrointestinal fiberscopy(GIF)revealed a reddish lesion in the lesser curvature of the upper stomach. Biopsy showed moderately differentiated adenocarcinoma. CT revealed swollen lymph nodes from the lesser curvature of the stomach to the para-aortic region. EUS-FNA was performed twice; however, histology revealed few atypical cells. A definitive diagnosis could not be obtained. Endoscopic findings revealed that the gastric cancer had invaded as far as the mucosa. Moreover, the swollen lymph nodes were considered to have originated from a different disease, such as lymphoma. The lesion of the stomach was an indication for ESD. On April 2016, ESD was performed, and histology revealed the following: Ⅱc, 31×23 mm, tub2, T1a(M), UL-, ly-, v-, VM0, and HM0. Incisional biopsy of the lymph nodes of the para-aorta was performed the followingmonth, and histology revealed poorly differentiated adenocarcinoma, which metastasized from gastric cancer. SOX therapy was performed in 10 courses. The para-aortic lymph nodes disappeared, and the number of lesser curvature lymph nodes decreased. On August 2018, follow-up GIF endoscopy was performed. A depressed mucosa was found in the lesser curvature of the gastric body, which was away from the ESD scar. Biopsy showed moderately differentiated adenocarcinoma. Total gastrectomy with lymph node dissection was performed on November 2018. Metastasis of the lesser curvature lymph nodes was positive; however, curative resection was performed histologically.

Correlation between the macroscopic severity of Crohn's disease in resected intestine and bowel wall thickness evaluated by water-immersion ultrasonography.

Objectives: Transabdominal ultrasonography is a common and accurate tool for managing Crohn's disease (CD); however, the significance of the resulting data is poorly understood. This study was performed to determine the association between bowel wall thickness evaluated by water-immersion ultrasonography and macroscopic severity, namely, refractory inflammation and subsequent fibrosis in CD surgical specimens.Materials and methods: We retrospectively evaluated 100 segments of colon and small intestine from 27 patients with CD. The resected specimens were placed in saline postoperatively, and bowel wall thickness was measured by water-immersion ultrasonography and compared with macroscopic findings. Correlations between bowel wall thickness and macroscopic findings were assessed using analysis of variance and receiver operating characteristic curves.Results: According to the progression of macroscopic severity, the mean bowel wall thickness was increased as follows: macroscopically intact: 4.1 mm, longitudinal ulcer scars: 5.4 mm, longitudinal open ulcers: 6.0 mm, large ulcers: 6.4 mm, cobblestone-like lesions: 7.1 mm, and fibrotic strictures: 7.4 mm. For all lesions except longitudinal ulcer scars, the bowel wall thickness was significantly thicker than that of macroscopically-intact areas (p < .001). According to receiver operating characteristic curves, bowel wall thickness >4.5 mm was associated with CD lesions, and thickness >5.5 mm was associated with more severe lesions.Conclusions: The bowel wall thickness of CD lesions was evaluated by water-immersion ultrasonography correlated with macroscopic disease severity.

[A Case of Lung Metastasis Occurring Four Years after Pancreaticoduodenectomy for Pancreatic Cancer].

The patient was a 68-year-old man who underwent pancreaticoduodenectomy for pancreatic cancer in 2011(T3N1M0, Stage Ⅲ). Fifty-one months after surgery, 2tumors measuring about 8mm in diameter were detected in the right lung. Thus, partial resection of the right lung was performed. Histological examination of both tumors revealed a tubular adenocarcinoma, with positive staining for CA19-9 and cytokeratin 7 and negative staining for cytokeratin 20, TTF-1, and napsin A, which were diagnosed as metastasis of pancreatic cancer. Twenty-nine months after the lung operation, he died because of peritoneal dissemination. Recurrent pancreatic cancer with metastasis has a particularly poor prognosis; however, surgical resection of lung metastasis in pancreatic cancer might result in a better prognosis.

Randomized trial of vonoprazan-based versus proton-pump inhibitor-based third-line triple therapy with sitafloxacin for Helicobacter pylori.

BACKGROUND AND AIM: This was a prospective, randomized trial of the efficacy of vonoprazan-based and proton-pump inhibitor-based 7-day triple regimens with amoxicillin and sitafloxacin as a third-line therapy for eradicating Helicobacter pylori after failure of clarithromycin-based and metronidazole-based first-line and second-line therapy. METHODS: We enrolled 63 patients positive for H. pylori in whom first-line and second-line regimens for eradicating failed. Patients were randomized to the V-AS group (vonoprazan 20-mg bid, amoxicillin 750-mg bid, and sitafloxacin 100-mg bid for 7 days) or PPI-AS group (esomeprazole 20-mg bid, rabeprazole 10-mg bid, or lansoprazole 30-mg bid; amoxicillin 750-mg bid; and sitafloxacin 100-mg bid for 7 days). We assessed the outcome of eradication therapy using the 13 C-urea breath test. We evaluated safety using patient questionnaires. This study was registered in the UMIN Clinical Trials Registry (UMIN000016336). RESULTS: The intention-to-treat and per-protocol eradication rates of V-AS were 75.8% (95% confidence interval [CI]: 57.7-88.9%) and 83.3% (95% CI: 65.3-94.4%), respectively. The respective eradication rates of PPI-AS were 53.3% (95% CI: 34.3-71.7%) and 57.1% (95% CI: 37.2-75.5%). In per-protocol analyses, the eradication rate of the V-AS group was significantly higher than that of the PPI-AS group (P = 0.043); however, no significant differences were observed in intention-to-treat analyses (P = 0.071). Questionnaire scores did not differ significantly between the groups. CONCLUSIONS: The findings suggest that 7-day triple therapy with vonoprazan, amoxicillin, and sitafloxacin is more effective than proton-pump inhibitor, amoxicillin, and sitafloxacin as a third-line regimen for eradicating H. pylori.

A quantification of calcaneal lateral plantar process position with implications for bipedal locomotion in Australopithecus.

The evolution of bipedalism in the hominin lineage has shaped the posterior human calcaneus into a large, robust structure considered to be adaptive for dissipating peak compressive forces and energy during heel-strike. A unique anatomy thought to contribute to the human calcaneus and its function is the lateral plantar process (LPP). While it has long been known that humans possess a plantarly positioned LPP and apes possess a more dorsally positioned homologous structure, the relative position of the LPP and intraspecific variation of this structure have never been quantified. Here, we present a method for quantifying relative LPP position and find that, while variable, humans have a significantly more plantar position of the LPP than that found in the apes. Among extinct hominins, while the position of the LPP in Australopithecus afarensis falls within the human distribution, the LPP is more dorsally positioned in Australopithecus sediba and barely within the modern human range of variation. Results from a resampling procedure suggest that these differences can reflect either individual variation of a foot structure/function largely shared among Australopithecus species, or functionally distinct morphologies that reflect locomotor diversity in Plio-Pleistocene hominins. An implication of the latter possibility is that calcaneal changes adaptive for heel-striking bipedalism may have evolved independently in two different hominin lineages.

Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to Helicobacter-Associated Gastric Epithelial Proliferation and Inflammation.

BACKGROUND/AIM: Although IL-6-mediated activation of the signal transduction and activator of transcription 3 (STAT3) axis is involved in inflammation and cancer, the role of STAT3 in Helicobacter-associated gastric inflammation and carcinogenesis is unclear. This study investigated the role of STAT3 in gastric inflammation and carcinogenesis and examined the molecular mechanism of Helicobacter-induced gastric phenotypes. METHODS: To evaluate the contribution of STAT3 to gastric inflammation and carcinogenesis, we used wild-type (WT) and gastric epithelial conditional Stat3-knockout (Stat3Δgec ) mice. Mice were infected with Helicobacter felis and euthanized at 18 months postinfection. Mouse gastric organoids were treated with recombinant IL-6 (rIL-6) or rIL-11 and a JAK inhibitor (JAKi) to assess the role of IL-6/STAT3 signaling in vitro. RESULTS: Inflammation and mucous metaplasia were more severe in WT mice than in Stat3Δgec mice. The epithelial cell proliferation rate and STAT3 activation were increased in WT mice. Application of rIL-6 and rIL-11 induced expression of intestinal metaplasia-associated genes, such as Tff2; this induction was suppressed by JAKi administration. CONCLUSIONS: Loss of STAT3 signaling in the gastric mucosa leads to decreased epithelial cell proliferation, atrophy, and metaplasia in the setting of Helicobacter infection. Therefore, activation of STAT3 signaling may play a key role in Helicobacter-associated gastric carcinogenesis.

Effects of Vonoprazan Compared with Esomeprazole on the Healing of Artificial Postendoscopic Submucosal Dissection Ulcers: A Prospective, Multicenter, Two-Arm, Randomized Controlled Trial.

BACKGROUND: Vonoprazan affords more clinical benefits than proton pump inhibitors (PPIs) during the healing of gastroduodenal ulcers. However, it remains controversial whether vonoprazan is more effective than PPIs when used to heal artificial ulcers arising after endoscopic submucosal dissection (ESD). AIM: This study investigated the effects of vonoprazan compared with esomeprazole on the healing of post-ESD artificial ulcers. METHODS: Sixty patients who underwent gastric ESD between May 2015 and May 2017 were randomized to treatment with vonoprazan (V group) or esomeprazole (E group) for 8 weeks. Upper endoscopy was performed at 4 and 8 weeks after ESD, and drug effects were estimated based on the ulcer healing rates and shrinkage rates. RESULTS: Fifty-three patients were analyzed. The respective 4- and 8-week ulcer healing rates did not differ significantly between V and E groups (8.0 versus 11.5%, P = 0.669; 88.9 versus 84.6%, P = 0.420). Similarly, the respective 4- and 8-week ulcer shrinkage rates did not differ significantly between V and E groups (96.8 versus 97.5%, P = 0.656; 100 versus 100%, P = 0.257). CONCLUSION: The healing of artificial ulcers after ESD did not differ using vonoprazan or esomeprazole. Both vonoprazan and esomeprazole were effective when used to promote artificial ulcer healing after ESD.

Correction to: Helicobacter-induced gastric inflammation alters the properties of gastric tissue stem/progenitor cells.

CORRECTION: Unfortunately, the original article [1] contained an error incorporated during production. A duplicated version of Table 1 was published in place of Table 2. Table 2 has been corrected in the original article and is also included correctly below.