Objective We evaluated the safety and efficacy of vonoprazan-based amoxicillin and clarithromycin 7-day triple therapy (VAC) in comparison to proton pump inhibitor (PPI)-based (PAC) as a first-line treatment and vonoprazan-based amoxicillin and metronidazole 7-day triple therapy (VAM) in comparison to PPI-based (PAM) as a second-line treatment for the eradication of Helicobacter pylori in Japan. Methods We performed a non-randomized, multi-center, parallel-group study to compare first-line VAC to PAC and second-line VAM to PAM. A pre-planned subgroup analysis on CAM resistance was also performed. Safety was evaluated with an adverse effects questionnaire (AEQ), which was completed by patients during therapy. Results The first-line eradication rates (ER) in the intention-to-treat (ITT) and per protocol (PP) analyses were 84.9% (95% CI: 81.9-87.6%, n=623) and 86.4% (83.5-89.1%, n=612), respectively, for VAC and 78.8% (75.3-82.0%, n=608) and 79.4% (76.0-82.6%, n=603), respectively, for PAC. The ER of VAC was higher than that of PAC in the ITT (p=0.0061) and PP analyses (p=0.0013). The ERs for VAC in patients with CAM-resistant and CAM-susceptible bacteria were 73.2% (59.7-84.2%, n=56) and 88.9% (83.4-93.1%, n=180), respectively. PAC was associated with higher AEQ scores for diarrhea, nausea, headache, and general malaise. In the second-line ITT and PP analyses VAM achieved ERs of 80.5% (74.6-85.6%, n=216) and 82.4% (76.6-87.3%, n=211), respectively, while PAM achieved ERs of 81.5% (74.2-87.4%, n=146) and 82.1% (74.8-87.9%, n=145), respectively. No significant differences were observed in the ITT (p=0.89) or PP (p=1.0) analyses. Conclusion The ER of first-line VAC was higher than that of PAC, but still <90%. No difference was observed between second-line VAM and PAM. Vonoprazan-based triple therapy was safe and well tolerated.

The eradication rate of V-AC treatment in the CAM-susceptible H. pylori-infected patients was <90%, as was that by PPI-AC, thus V-AC is not ideal regimen in CAM-susceptible H. pylori. However, the 82.9% eradication rate of V-AC in the CAM-resistant infections may indicate the potential of V-AC with modified dose, dosing interval, and treatment duration. (UMIN000016337).

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.

Sonazoid (Daiichi Sankyo, Tokyo, Japan), a second-generation of a lipid-stabilized suspension of a perfluorobutane gas microbubble contrast agent, has been used clinically in patients with liver tumors and for harmonic gray-scale ultrasonography (US) in Japan since January 2007. Sonazoid-enhanced US has two phases of contrast enhancement: vascular and late. In the late phase of Sonazoid-enhanced US, we scanned the whole liver using this modality at a low mechanical index (MI) without destroying the microbubbles, and this method allows detection of small viable hepatocellular carcinoma (HCC) lesions which cannot be detected by conventional US as perfusion defects in the late phase. Re-injection of Sonazoid into an HCC lesion which previously showed a perfusion defect in the late phase is useful for confirming blood flow into the defects. High MI intermittent imaging at 2 frames per second in the late phase is also helpful in differentiation between necrosis and viable hypervascular HCC lesions. Sonazoid-enhanced US by the coded harmonic angio mode at a high MI not only allows clear observation of tumor vessels and tumor enhancement, but also permits automatic scanning with Sonazoid-enhanced three dimensional (3D) US. Fusion images combining US with contrast-enhanced CT or contrast-enhanced MRI have made it easy to detect typical or atypical HCC lesions. By these methods, Sonazoid-enhanced US can characterize liver tumors, grade HCC lesions histologically, recognize HCC dedifferentiation, evaluate the efficacy of ablation therapy or transcatheter arterial embolization, and guide ablation therapy for unresectable HCC. This article reviews the current developments and applications of Sonazoid-enhanced US and Sonazoid-enhanced 3D US for diagnosing and treating hepatic lesions, especially HCC.

The palaeobiological record of 12 million to 7 million years ago (Ma) is crucial to the elucidation of African ape and human origins, but few fossil assemblages of this period have been reported from sub-Saharan Africa. Since the 1970s, the Chorora Formation, Ethiopia, has been widely considered to contain ~10.5 million year (Myr) old mammalian fossils. More recently, Chororapithecus abyssinicus, a probable primitive member of the gorilla clade, was discovered from the formation. Here we report new field observations and geochemical, magnetostratigraphic and radioisotopic results that securely place the Chorora Formation sediments to between ~9 and ~7 Ma. The C. abyssinicus fossils are ~8.0 Myr old, forming a revised age constraint of the human-gorilla split. Other Chorora fossils range in age from ~8.5 to 7 Ma and comprise the first sub-Saharan mammalian assemblage that spans this period. These fossils suggest indigenous African evolution of multiple mammalian lineages/groups between 10 and 7 Ma, including a possible ancestral-descendent relationship between the ~9.8 Myr old Nakalipithecus nakayamai and C. abyssinicus. The new chronology and fossils suggest that faunal provinciality between eastern Africa and Eurasia had intensified by ~9 Ma, with decreased faunal interchange thereafter. The Chorora evidence supports the hypothesis of in situ African evolution of the Gorilla-Pan-human clade, and is concordant with the deeper divergence estimates of humans and great apes based on lower mutation rates of ~0.5 × 10(-9) per site per year (refs 13 - 15).

Aim To assess the efficacy of 7-day first-line Helicobacter pylori eradication with vonoprazan (VPZ), clarithromycin (CAM), and metronidazole (MNZ) in patients with penicillin allergy. Methods Patients with penicillin allergy, diagnosed with Helicobacter pylori infection and did not have history of Helicobacter pylori eradication, were eligible for the study. Twenty patients were prospectively treated with 20 mg VPZ twice daily, 200 or 400 mg CAM twice daily, and 250 mg MNZ twice daily for 7 days. We also collected the data from 30 patients retrospectively treated with proton pump inhibitor (PPI), CAM, and MNZ. Safety was evaluated in patients completing an adverse effect questionnaire. Results Both the intention-to-treat and per-protocol effectiveness of VPZ-based eradication were 100% (95% CI: 86.1–100%; n = 20). The eradication rates of PPI-based regimen were 83.3% (95% CI: 65.3–94.4%) in the ITT and 82.7% (95% CI: 64.2–94.2%) in the PP analyses. Abdominal fullness was more frequent in VCM compared to PCM. However, all patients with VCM regimen had taken 100% of their course of medication. Conclusion Triple therapy with VPZ, CAM, and MNZ is well tolerated and effective for eradicating Helicobacter pylori in patients allergic to penicillin. This study was registered in the UMIN Clinical Trials Registry as UMIN000016335.

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Objective To investigate the short-and long-term efficacy and safety of infliximab (IFX) in intestinal Behçet's disease (BD) patients in a retrospective cohort study. Methods Among 43 consecutive patients with intestinal BD presenting at the same clinic, 15 with active disease and receiving standard treatment were given IFX infusions (5 mg/kg body weight) every eight weeks. The patients were clinically and endoscopically evaluated before treatment, then assessed after 10 weeks, 12 months and 24 months for a clinical response, defined as a significant improvement in intestinal symptoms and a reduced C-reactive protein (CRP) level. Results At week 10, 12 patients (80%) exhibited a response to IFX, with eight (53%) in remission with no intestinal symptoms and normal CRP levels. A response to IFX was maintained in seven of the 11 patients (64%) available at 12 months and in four of the eight patients (50%) available at 24 months. Of the seven patients receiving prednisolone at entry, five responders had their steroid doses reduced. Fulminant intestinal BD was predictive of an absence of response to IFX. The adverse effects comprised one infusion reaction and one case of fever, most likely related to IFX. Conclusion IFX is effective and safe in patients with refractory intestinal BD.