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Many clinical trials have been conducted for inflammatory bowel disease (IBD), so various clinical indices (CIs) and endoscopic indices (EIs) have also been evaluated. However, recently, with the progress of IBD management, review of established indices from previous studies, and establishment of new indices, the landscape of the use of indices in clinical trials have changed. We investigated the number and frequency of the indices adapted in recent clinical trials for ulcerative colitis (CI and EI) and Crohn’s disease (CI, EI, index related to magnetic resonance imaging, index for evaluating patient-reported outcomes, and health-related quality of life). Based on the results, we selected representative indices and further reviewed their content and characteristics. Moreover, various definitions, including clinical and endoscopic response or remission, have been described by means of representative indices in clinical trials.

Noninvasive biomarkers of intestinal inflammation can reduce the number of endoscopies in children with inflammatory bowel disease (IBD). This study aimed to prospectively investigate the usefulness of fecal calprotectin (FCP) and fecal immunochemical test (FIT) in pediatric IBD.Patients aged 6-17 years who underwent ileocolonoscopy for established or suspected IBD were eligible for this study. Fecal samples for FCP and FIT were collected before colonoscopy.A total of 251 samples were analyzed: 88 from ulcerative colitis (UC), 74 from Crohn's disease (CD), 75 from healthy controls (HC), and 14 from children with functional gastrointestinal disorders and normal colonoscopy (NC). At IBD diagnosis, both FCP and FIT were significantly higher in the newly diagnosed UC/CD group than in the HC/NC group (P 0.001). The optimal cutoffs of FCP and FIT to predict IBD diagnosis were 217 mg/kg and 87 ng/mL, respectively. Patients without mucosal healing (MH) showed higher FCP and FIT than those with MH in both UC and CD (P 0.001). The FCP increased exponentially as the endoscopic activity score increased. The optimal cutoff values of FCP and FIT for predicting MH were 161 mg/kg and 106 ng/mL for UC and 367 mg/kg and 57 ng/mL for CD, respectively. FCP showed better specificity than the FIT. Patients with CD and normal ileocolonoscopy had elevated FCP during active small intestinal inflammation.Both FCP and FIT correlate well with endoscopic activity in pediatric patients with IBD. The FCP is a superior marker for predicting MH.

The Epstein-Barr virus (EBV) infection status in patients with inflammatory bowel disease (IBD), particularly those using thiopurines, may be associated with the risk of lymphoproliferative disorder and hemophagocytic lymphohistiocytosis. This was the first multicenter survey of EBV infection in Japanese patients with IBD. Factors related to the EBV infection status were also investigated.Five tertiary institutions in Japan participated in this study to examine pediatric and adult patients with IBD. Serum EBV anti-viral capsid antigen (VCA) IgG, EBV anti-VCA IgM, and anti-EBV nuclear antigen-antibody were measured in 495 patients with IBD. The patients' information was obtained from their medical records. Prior EBV infection was defined as anti-VCA IgM negativity and anti-VCA IgG positivity (UMIN000033004).The patients' median age was 25 years (range 0-92 years). Of the 495 patients, nine were anti-VCA IgM-positive and 354 were anti-VCA IgG-positive (seroprevalence: 72.8%). The proportion of patients with prior EBV infection was 0% for those aged 5 years, 60% for those aged 30 years, and 90% for those aged 30 years. The proportion of EBV-uninfected patients using thiopurines was 28.4% (52/183) for all patients and 51.8% (44/85) for pediatric patients. Age was significantly associated with anti-VCA IgG seropositivity (p 0.01, odds ratio: 0.902, 95% confidence interval: 0.880-0.925). No cases of lymphoproliferative disorder, hemophagocytic lymphohistiocytosis, or chronic active EBV infection were reported.Approximately 30% of Japanese patients with IBD were EBV-uninfected, including those using thiopurines. Age was a significant factor for anti-VCA IgG seropositivity.

Background Fecal microbiota transplantation (FMT) in patients with ulcerative colitis has shown variable efficacy depending on the protocol used. A previous randomized controlled trial reported that anaerobic preparation of donor stool contributes to improved efficacy. Despite the suggestion that viable obligate anaerobes would be decreased through aerobic handling, there have been only a limited number of reports on how these aerobic or anaerobic procedures affect the composition of viable microbiota in the fecal slurries used for FMT. Methods We adopted 16S and 23S rRNA-targeted reverse transcription-quantitative polymerase chain reaction to quantify viable bacteria in fecal slurries. This study utilized specific primers designed to detect obligate anaerobes (including Clostridium coccoides group, C. leptum subgroup, Bacteroides fragilis group, Bifidobacterium, Atopobium cluster, and Prevotella) and facultative anaerobes (including total lactobacilli, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus). We then calculated the ratio change (RC) between before and after mixing, and compared the resulting values between anaerobic-prep and aerobic-prep in samples fixed immediately after blending (RCAn0 vs. RCAe0) and in samples maintained (under anaerobic or aerobic conditions) for 1 h after blending (RCAn1 vs. RCAe1). Results For most obligate anaerobes, the median RC tended to be less than 1, indicating that the number of obligate anaerobes was decreased by the blending procedure. However, in samples maintained for 1 h after blending, anaerobic-prep counteracted the decrease otherwise seen for the C. coccoides group and B. fragilis groups (P C. leptum subgroup also tended to show higher RC by anaerobic-prep than by aerobic-prep, although this effect was not statistically significant. Among facultative anaerobes, Enterobacteriaceae, Enterococcus, and Staphylococcus showed median RC values of more than 1, indicating that these organisms survived and even grew after mixing. Moreover, oxygen exposure had no significant influence on the survival of the facultative anaerobes. Conclusions The conditions under which the blending procedure was performed affected the proportion of live anaerobes in fecal slurries. The obligate anaerobes tended to be decreased by blending processes, but anaerobic-prep significantly mitigated this effect. Anaerobic-prep may improve the efficacy of FMT by permitting the efficient transfer of obligate anaerobes to patients with ulcerative colitis.

Although indigo naturalis (IN) is effective for patients with active ulcerative colitis (UC), IN was associated with adverse events (AEs), including pulmonary arterial hypertension (PAH). Our aim was to evaluate the occurrence of IN-associated AEs and to evaluate any IN dose–effect on AEs. A nationwide survey, using questionnaires, was conducted by conducted by the research group funded by the Ministry of Health, Labour and Welfare of Japan, between June 2017 and September 2018. A first questionnaire determined the occurrence of AEs associated with the therapeutic use of IN or herbal medicines containing IN in patients with UC. A second survey identified the clinical characteristics of patients who developed IN-associated critical AEs, namely, liver dysfunction, PAH, and intussusception. Across 337 participating institutions, 49,320 patients with UC were identified, with IN used in 877 (1.8%). AEs were reported in 91 patients (107 events), including liver dysfunction (n = 40), gastrointestinal symptoms (n = 21), headache (n = 13), and PAH (n = 11). No dose–effect relationship between IN and AEs was identified. Liver dysfunction tended to be mild and reversible. Ten cases of intussusception were reported, with 40% of these patients requiring surgical resection. IN-induced PAH was recovered in patients who discontinued to use IN. No IN-associated deaths were reported. IN-associated AEs were identified among patients with UC, with liver dysfunction often being reversible, while surgical resection was required in a high proportion of patients who developed intussusception. Both healthcare workers and patients should adequately recognize the potential for AEs with the use of IN.

In this paper we study the (in)approximability of two distance-based relaxed variants of the maximum clique problem (Max Clique), named Max d-Clique and Max d-Club: A d-clique in a graph $$G = (V, E)$$ is a subset $$S\subseteq V$$ of vertices such that for every pair of vertices $$u, v\in S$$ , the distance between u and v is at most d in G. A d-club in a graph $$G = (V, E)$$ is a subset $$S'\subseteq V$$ of vertices that induces a subgraph of G of diameter at most d. Given a graph G with n vertices, the goal of Max d-Clique (Max d-Club, resp.) is to find a d-clique (d-club, resp.) of maximum cardinality in G. Since Max 1-Clique and Max 1-Club are identical to Max Clique, the inapproximabilty for Max Clique shown by Zuckerman in 2007 is transferred to them. Namely, Max 1-Clique and Max 1-Club cannot be efficiently approximated within a factor of $$n^{1-\varepsilon }$$ for any $$\varepsilon > 0$$ unless $$\mathcal{P} = \mathcal{NP}$$ . Also, in 2002, Marin $$\breve{\mathrm{c}}$$ ek and Mohar showed that it is $$\mathcal{NP}$$ -hard to approximate Max d-Club to within a factor of $$n^{1/3-\varepsilon }$$ for any $$\varepsilon >0$$ and any fixed $$d\ge 2$$ . In this paper, we strengthen the hardness result; we prove that, for any $$\varepsilon > 0$$ and any fixed $$d\ge 2$$ , it is $$\mathcal{NP}$$ -hard to approximate Max d-Club to within a factor of $$n^{1/2-\varepsilon }$$ . Then, we design a polynomial-time algorithm which achieves an optimal approximation ratio of $$O(n^{1/2})$$ for any integer $$d\ge 2$$ . By using the similar ideas, we show the $$O(n^{1/2})$$ -approximation algorithm for Max d-Clique for any $$d\ge 2$$ . This is the best possible in polynomial time unless $$\mathcal{P} = \mathcal{NP}$$ , as we can prove the $$\varOmega (n^{1/2-\varepsilon })$$ -inapproximability.

The ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) are surrogate markers of arteriosclerosis. However, their roles in patients with acute ischemic stroke remain unclear. From October 2003 to September 2011, we enrolled patients with arteriosclerotic ischemic stroke (AIS) exhibiting large infarcts attributed to large-artery atherosclerosis (LAA) or deep subcortical infarcts (mainly lacunar infarcts) attributed to small-artery disease (SAD). Outpatients without a history of stroke served as controls (CTL). We divided the study period into two terms and assessed patients using two different oscillometric devices (Form PWV/ABI, Omron Colin; and VaSera VS-1500, Fukuda Denshi) in each term. One-way analysis of variance and age- and sex-adjusted analysis of covariance were used to compare the three groups. We analyzed 842 patients. The ABI was significantly lower in the LAA (n = 102) group than in the SAD (n = 280) and CTL (n = 460) groups. The baPWV was significantly higher in the LAA and SAD groups than in the CTL group. The CAVI gradually increased in the order of CTL, SAD and LAA. The cutoff values of baPWV and CAVI for detection of AIS were 18.3 m s(-1) (odds ratio (OR): 6.09, 95% confidence interval (CI): 3.97-9.62, P0.01) and 9.5 (OR: 1.44, 95% CI: 1.24-1.70, P0.001), respectively. Among the three indicators, a lower ABI indicated advanced atherosclerosis associated with LAA, and an increased baPWV more closely indicated AIS. An increased CAVI may indicate the degree of vessel stiffness due to arteriosclerosis.

It is still unclear whether silent brain infarct (SBI) and white-matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) scans are associated with cardio-ankle vascular index (CAVI), a novel parameter of arterial stiffness. We studied 220 consecutive patients (mean age, 69 years) without a history of stroke or transient ischemic attack. Patients were assessed for the presence of SBI, WMHs and risk factors. Arterial stiffness was evaluated using CAVI. Patients were categorized into one of two groups according to the presence or absence of SBI and WMHs, and clinical characteristics were compared between the two groups. CAVI was significantly higher in patients with SBI or in patients with WMHs than in those without those respective findings. The CAVI cutoff values for detection of SBI and WMHs were 9.2 and 8.9, respectively. On multivariable analyses, CAVI, a one point increase in CAVI: odds ratio (OR), 1.25; 95% confidence interval (CI), 1.01-1.56; CAVI ≥9.2: OR, 2.34; 95% CI, 1.16-5.02, was independently associated with SBI, however, CAVI was not independently associated with WMHs. Patients with CAVI ≥9.2 had higher OR for the presence of both SBI and WMHs (OR, 2.57; 95% CI, 1.15-5.98) when compared with patients with CAVI