Diagnostic approach for patients with unidentified fever according to the classical criteria of fever of unknown origin in the field of autoimmune disorders

ArticleImmunological medicine. 42(4): 176-184 (2019)journal articl

Long-term maintenance of the mucosal healing induced by azacitidine therapy in a patient with intestinal Behçet's-like disease accompanied with myelodysplastic syndrome involving trisomy 8

ArticleImmunological medicine. 42(3): 135-141 (2019)journal articl

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study

Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. Methods: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. Results: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). Conclusions: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression

A nationwide, multi-center, retrospective study of symptomatic small bowel stricture in patients with Crohn\u27s disease.

BACKGROUND:Small bowel stricture is one of the most common complications in patients with Crohn\u27s disease (CD). Endoscopic balloon dilatation (EBD) is a minimally invasive treatment intended to avoid surgery; however, whether EBD prevents subsequent surgery remains unclear. We aimed to reveal the factors contributing to surgery in patients with small bowel stricture and the factors associated with subsequent surgery after initial EBD.METHODS:Data were retrospectively collected from surgically untreated CD patients who developed symptomatic small bowel stricture after 2008 when the use of balloon-assisted enteroscopy and maintenance therapy with anti-tumor necrosis factor (TNF) became available.RESULTS:A total of 305 cases from 32 tertiary referral centers were enrolled. Cumulative surgery-free survival was 74.0% at 1 year, 54.4% at 5 years, and 44.3% at 10 years. The factors associated with avoiding surgery were non-stricturing, non-penetrating disease at onset, mild severity of symptoms, successful EBD, stricture length < 2 cm, and immunomodulator or anti-TNF added after onset of obstructive symptoms. In 95 cases with successful initial EBD, longer EBD interval was associated with lower risk of surgery. Receiver operating characteristic analysis revealed that an EBD interval of ≤ 446 days predicted subsequent surgery, and the proportion of smokers was significantly high in patients who required frequent dilatation.CONCLUSIONS:In CD patients with symptomatic small bowel stricture, addition of immunomodulator or anti-TNF and smoking cessation may improve the outcome of symptomatic small bowel stricture, by avoiding frequent EBD and subsequent surgery after initial EBD

Uptake and Advanced Therapy of Butyrate in Inflammatory Bowel Disease

The pathogenesis and refractory nature of inflammatory bowel disease (IBD) are related to multiple factors, including genetic factors, environmental factors, and abnormalities in gut microbial diversity, which lead to decreased levels of short-chain fatty acids (SCFAs). Among SCFAs, butyrate plays an important role in mucosal barrier maintenance, serves as an energy source in intestinal epithelial cells (IECs), and exhibits anti-inflammatory effects; therefore, it is a particularly important factor in gut homeostasis. Changes in gut microbiota and butyrate levels affect the outcomes of drug therapy for IBD. Butyrate is mainly absorbed in the large intestine and is transported by monocarboxylate transporter 1 (MCT1) and sodium-coupled monocarboxylate transporter 1 (SMCT1). During gut inflammation, butyrate utilization and uptake are impaired in IECs. Dysbiosis and low abundance of butyrate affect fecal microbiota transplantation and anticancer immunotherapy. Although butyrate administration has been reported as a treatment for IBD, its effects remain controversial. In this review, we discuss butyrate absorption and metabolism in patients with IBD and their relationship with drug therapy

Takayasu arteritis presenting with fever of unknown origin and bilateral carotid artery tenderness: A case report

A 51-year-old otherwise healthy woman was referred to our hospital with a fever of unknown origin, liver dysfunction, and anemia. One month prior, she had persistent and spontaneous anterior neck pain, with no exacerbation during swallowing or neck movements. Physical examination revealed no pharyngeal or tonsillar abnormalities, heart murmur, arthritis, skin rash, or lymphadenopathy, except for mild bilateral common carotid artery tenderness at the level of the thyroid cartilage. Blood tests showed nonspecific chronic inflammatory findings, anemia, and liver damage, whereas blood cultures, viral antibodies, interferon-γ release assay, and antibodies specific for any collagen disease showed negative results. Echocardiography and computed tomography without contrast of the neck, chest, abdomen, and pelvis showed no apparent abnormalities. She was subsequently diagnosed with Takayasu arteritis using positron emission tomography. Identifying a characteristic history of bilateral carotid artery tenderness and subsequent positron emission tomography can be useful for diagnosing Takayasu arteritis

A trial deep learning-based model for four-class histologic classification of colonic tumor from narrow band imaging

Abstract Narrow band imaging (NBI) has been extensively utilized as a diagnostic tool for colorectal neoplastic lesions. This study aimed to develop a trial deep learning (DL) based four-class classification model for low-grade dysplasia (LGD); high-grade dysplasia or mucosal carcinoma (HGD); superficially invasive submucosal carcinoma (SMs) and deeply invasive submucosal carcinomas (SMd) and evaluate its potential as a diagnostic tool. We collected a total of 1,390 NBI images as the dataset, including 53 LGD, 120 HGD, 20 SMs and 17 SMd. A total of 598,801 patches were trimmed from the lesion and background. A patch-based classification model was built by employing a residual convolutional neural network (CNN) and validated by three-fold cross-validation. The patch-based validation accuracy was 0.876, 0.957, 0.907 and 0.929 in LGD, HGD, SMs and SMd, respectively. The image-level classification algorithm was derived from the patch-based mapping across the entire image domain, attaining accuracies of 0.983, 0.990, 0.964, and 0.992 in LGD, HGD, SMs, and SMd, respectively. Our CNN-based model demonstrated high performance for categorizing the histological grade of dysplasia as well as the depth of invasion in routine colonoscopy, suggesting a potential diagnostic tool with minimal human inputs

Daidzein Intake Is Associated with Equol Producing Status through an Increase in the Intestinal Bacteria Responsible for Equol Production

Equol is a metabolite of isoflavone daidzein and has an affinity to estrogen receptors. Although equol is produced by intestinal bacteria, the association between the status of equol production and the gut microbiota has not been fully investigated. The aim of this study was to compare the intestinal bacteria responsible for equol production in gut microbiota between equol producer and non-producer subjects regarding the intake of daidzein. A total of 1044 adult subjects who participated in a health survey in Hirosaki city were examined. The concentration of equol in urine was measured by high-performance liquid chromatography. The relative abundances of 8 bacterial species responsible for equol production in the gut microbiota was assessed using 16S rRNA amplification. There were 458 subjects identified as equol producers. The proportion of equol production status and the intake of daidzein increased with age. Daily intake of daidzein was larger in equol-producer. The intestinal bacteria, which convert daidzein to equol were present in both equol producers and non-producers. However, the relative abundance and the prevalence of Asaccharobacter celatus and Slackia isoflavoniconvertens were significantly higher in equol producers than those in equol non-producers. The intestinal bacteria that convert daidzein to equol are present in not only the equol producers but also in the non-producers. The daidzein intake is associated with the equol production status through an increase of A. celatus and S. isoflavoniconvertens in the gut microbiota

A Cohort Study of the Influence of the 12-Component Modified Japanese Diet Index on Oral and Gut Microbiota in the Japanese General Population

The Japanese diet is a healthy dietary pattern, and the oral or gut microbiota have been identified as the main factors underlying the beneficial effects of the Japanese diet. However, epidemiological studies on Japanese dietary patterns calculated from daily eating habits in the general population yielded inconsistent findings. This study aimed to determine the association between the 12-component modified Japanese Diet Index (mJDI12) and the oral and gut microbiota in the general population of a rural area in Japan. After propensity-score matching, 396 participants (198 each in the low and high mJDI12 groups) were picked out. One year after the follow up survey, we reclassified the subjects and compared the low and high mJDI12 groups again. Participants with a high mJDI12 had a higher relative abundance of butyric acid-producing bacteria in their gut microbiota. Moreover, the significantly higher dietary fiber intake in the high mJDI12 group suggested that the high intake of dietary fiber contributed to an increase in butyric acid-producing bacteria in the gut. In contrast, in individuals with a high mJDI12, only Allpprevotella was decreased in the oral microbiota. Thus, the Japanese dietary pattern can have beneficial effects by improving the oral and gut microbiota

A Cohort Study of the Effects of Daily-Diet Water-Soluble Dietary Fiber on Butyric Acid-Producing Gut Microbiota in Middle-Aged and Older Adults in a Rural Region

Water-soluble dietary fiber is primarily a substrate for degradation of short chain fatty acids (SCFAs), particularly butyric acid, by gut microbiota. SCFAs have beneficial effects on the whole body. However, epidemiological studies on the association between water-soluble dietary fiber from daily food intake and butyric acid-producing bacteria are inconsistent. The purpose of this study was to determine the association between levels of water-soluble dietary fiber from daily food intake and gut microbiota, particularly butyric acid producers, in middle-aged and older adults in a rural area in Japan. We examined the effects of water-soluble dietary fiber intake on gut microbiota after adjusting for confounding factors. After propensity score matching, 520 subjects (260 in the low-intake group and 260 in the high-intake group) were selected. One year later after a follow-up survey, we re-classified the participants and again compared low- and high-intake groups. As a result, people with a high intake had a higher relative abundance of butyric acid-producing bacteria. It was also revealed that butyric acid-producing bacteria remained high in the group that maintained high intake the next year. We concluded that continuous intake of water-soluble dietary fiber from daily food is necessary to maintain sufficient amounts of butyric acid-producing bacteria