Background
Adrenomedullin (AM) is a bioactive peptide having many pleiotropic effects, including mucosal healing and immunomodulation. AM has shown beneficial effects in rodent models and in ...preliminary study for patients with ulcerative colitis (UC). We performed a clinical trial to investigate the efficacy and safety of AM in patients with UC.
Methods
This was a multi-center, double-blind, placebo-controlled phase-2a trial evaluating 28 patients in Japan with steroid-resistant UC. Patients were randomly assigned to four groups and given an infusion of 5, 10, 15 ng/kg/min of AM or placebo for 8 h per day for 14 days. The primary endpoint was the change in Mayo scores at 2 weeks. Main secondary endpoints included the change in Mayo scores and the rate of clinical remission at 8 weeks, defined as a Mayo score 0.
Results
No differences in the primary or secondary endpoints were observed among the four groups at 2 weeks. Despite the insufficient tracking rate, the Mayo score at 8 weeks was only significantly decreased in the high-dose AM group (15 ng/kg/min) compared with the placebo group (− 9.3 ± 1.2 vs. − 3.0 ± 2.8,
P
= 0.035), with its rate of clinical remission at 8 weeks being significantly higher (3/3, 100% vs. 0/2, 0%,
P
= 0.025). We noted mild but no serious adverse events caused by the vasodilatory effect of AM.
Conclusions
In this double-blind randomized trial, we observed the complete remission at 8 weeks in patients with steroid-resistant UC receiving a high dose of AM.
Clinical trial registry
JAPIC clinical trials information; Japic CTI-205255 (200410115290).
https://www.clinicaltrials.jp/cti-user/trial/Search.jsp
.
Background
Capsule endoscopy can be used to identify the early stage of small bowel Crohn’s disease (CD). We evaluated significant small bowel capsule endoscopy (SBCE) findings that can lead to early ...diagnosis of CD.
Methods
We retrospectively accumulated clinical and SBCE data of 108 patients (63 with and 45 without CD). Types of small bowel mucosal injuries, including erosion, ulceration, and cobblestone appearance, and the alignment of diminutive lesions were compared between patients with and without CD. Inter- and intra-observer agreement in the determination of lesions was assessed in 25 pairs of SBCE from the two groups.
Results
Under SBCE, cobblestone appearance (33% vs. 2%,
p
< 0.0001), longitudinal ulcers (78% vs. 20%,
p
< 0.0001), and irregular ulcers (84% vs. 60%,
p
< 0.01) were more frequently found in patients with CD. Linear erosion (90% vs. 38%,
p
< 0.0001) and irregular erosion (89% vs. 64%,
p
< 0.005) were also more frequent in patients with CD. Furthermore, circumferential (75% vs. 9%,
p
< 0.0001) and longitudinal (56% vs. 7%,
p
< 0.0001) alignment of diminutive lesions, mainly observed in the 1st tertile of the small bowel, was more frequent in patients with CD. Good intra-observer agreement was found for ulcers, cobblestone appearance, and lesion alignment. However, inter-observer agreement of SBCE findings differed among observers.
Conclusions
Circumferential or longitudinal alignment of diminutive lesions, especially in the upper small bowel, may be a diagnostic clue for CD under SBCE, while inter-observer variations should be cautiously considered when using SBCE.
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by clonal myeloproliferation, progressive bone marrow (BM) fibrosis, splenomegaly, and anemia. BM fibrosis was ...previously thought to be a reactive phenomenon induced by mesenchymal stromal cells that are stimulated by the overproduction of cytokines such as transforming growth factor (TGF)-β1. However, the involvement of neoplastic fibrocytes in BM fibrosis was recently reported. In this study, we showed that the vast majority of collagen- and fibronectin-producing cells in the BM and spleens of Jak2V617F-induced myelofibrosis (MF) mice were fibrocytes derived from neoplastic hematopoietic cells. Neoplastic monocyte depletion eliminated collagen- and fibronectin-producing fibrocytes in BM and spleen, and ameliorated most characteristic MF features in Jak2V617F transgenic mice, including BM fibrosis, anemia, and splenomegaly, while had little effect on the elevated numbers of megakaryocytes and stem cells in BM, and leukothrombocytosis in peripheral blood. TGF-β1, which was produced by hematopoietic cells including fibrocytes, promoted the differentiation of neoplastic monocytes to fibrocytes, and elevated plasma TGF-β1 levels were normalized by monocyte depletion. Collectively, our data suggest that neoplastic fibrocytes are the major contributor to BM fibrosis in PMF, and TGF-β1 is required for their differentiation.
Backgrounds
The present study sought to establish a standard third-line eradication regimen for
Helicobacter pylori
in Japan.
Methods
Subjects were 204 patients with
H. pylori
infection in whom the ...standard Japanese first- and second-line eradication therapies had proven unsuccessful. Patients were randomly assigned to one of the following third-line eradication therapy groups: (1) LA group: lansoprazole (LPZ) 30 mg 4 times a day (qid) + amoxicillin (AMPC) 500 mg qid for two weeks; (2) LAL group: LPZ 30 mg twice a day (bid) + AMPC 750 mg bid + levofloxacin (LVFX) 300 mg bid for one week; (3) LAS group: LPZ 30 mg bid + AMPC 750 mg bid + sitafloxacin (STFX) 100 mg bid for one week. Patients for whom these therapies failed underwent a crossover fourth-line eradication regimen. Drug sensitivity was also tested for AMPC, clarithromycin (CAM), MNZ, LVFX, and STFX.
Results
Drug resistance rates prior to third-line eradication therapy were 86.4 % for CAM, 71.3 % for MNZ, 57.0 % for LVFX, 8.2 % for AMPC, and 7.7 % for STFX. Intention-to-treat analysis of third-line eradication therapy eradication rates showed a significantly higher rate in the LAS group (70.0 %) compared with the LA group (54.3 %;
p
< 0.05) and the LAL group (43.1 %;
p
< 0.001). The significantly lower rate in the LAL group than the LAS group was caused by bacterial resistance to LVFX.
Conclusions
The findings suggest that triple therapy with PPI, AMPC, and STFX for one week would be an effective standard third-line eradication regimen for
H. pylor
i in Japan.
Luteibacter jiangsuensis is a gram-negative aerobic bacillus that was first isolated from soil samples at a pesticide factory in China and reported in 2011. Here, we describe the first case of L. ...jiangsuensis infection in human.
A 59-year-old Japanese woman undergoing treatment for Crohn's disease was admitted to our hospital with fever. Clinical examination indicated catheter-related bloodstream infection. The catheter was removed and meropenem was initiated. Morphologically identical glucose non-fermentative gram-negative bacilli were detected from two sets of aerobic blood culture and catheter-tip cultures. MALDI-TOF mass spectrometry failed to identify the bacterium, which was later identified as L. jiangsuensis by 16 S rRNA gene sequencing. Antimicrobial susceptibility test revealed that the isolate was resistant to carbapenem, therefore meropenem was switched to intravenous levofloxacin (500 mg/day). After 14 days of treatment with levofloxacin, the patient was discharged.
This is the first case of L. jiangsuensis infection in human. The strain was identified by 16 S rRNA gene sequence analysis.
We reported a notable case of inflammatory hepatocellular adenoma that grew during pregnancy, consequently changing its appearance on magnetic resonance imaging remarkably. A 5-months-pregnant ...35-year-old woman presented with a 37-mm liver nodule that had been diagnosed as focal nodular hyperplasia 3 years earlier. She had never used oral contraceptives. After 2 months, the nodule grew to 57 mm. The patient delivered a full-term infant without complications. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging performed after delivery revealed markedly different findings compared with the first images. A liver biopsy was performed, and the tumor was diagnosed as inflammatory hepatocellular adenoma.
Background and Aim
Adrenomedullin is a bioactive peptide with many pleiotropic effects, including mucosal healing and immunomodulation. Adrenomedullin has shown beneficial effects in rodent models of ...inflammatory bowel disease and, more importantly, in clinical trials including patients with ulcerative colitis. We performed a successive clinical trial to investigate the efficacy and safety of adrenomedullin in patients with Crohn's disease (CD).
Methods
This was a multicenter, double‐blind, placebo‐controlled phase 2a trial that evaluated 24 patients with biologic‐resistant CD in Japan. Patients were randomly assigned to three groups and were given an infusion of 10 or 15 ng/kg/min of adrenomedullin or placebo for 8 h per day for 7 days. The primary endpoint was the change in the CD activity index (CDAI) at 8 weeks. The main secondary endpoints included changes in CDAI from week 4 to week 24.
Results
No differences in the primary or secondary endpoints were observed between the three groups by the 8th week. Changes in CDAI in the placebo group gradually decreased and disappeared at 24 weeks, but those in the adrenomedullin‐treated groups (10 or 15 ng/kg/min group) remained at steady levels for 24 weeks. Therefore, a significant difference was observed between the placebo and adrenomedullin‐treated groups at 24 weeks (P = 0.043) in the mixed‐effects model. We noted mild adverse events caused by the vasodilatory effect of adrenomedullin.
Conclusion
In this trial, we observed a long‐lasting (24 weeks) decrease in CDAI in the adrenomedullin‐treated groups. Adrenomedullin might be beneficial for biologic‐resistant CD, but further research is needed.
Although a few reports of neuroendocrine tumor (NET) in the stomach or appendix with surrounding micronests have been published, cases of rectal NET are rare. We herein report a unique case of a ...patient with single rectal NET treated endoscopically. A pathological examination revealed multiple endocrine cell micronests (ECMs) in the submucosal layer around the main NET lesion. Neither lymph node metastasis nor distant metastasis in computed tomography was observed six years after the treatment. Because case reports of multiple ECM are very rare, the significance of malignancy is unclear. It therefore appears to be necessary to accumulate similar cases.
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