Anti-inflammatory Effects of Bacteroidota Strains Derived From Outstanding Donors of Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis.

BACKGROUND: The proportion of certain Bacteroidota species decreased in patients with ulcerative colitis, and the recovery of Bacteroidota is associated with the efficacy of fecal microbiota transplantation therapy. We hypothesized that certain Bacteroidota may advance ulcerative colitis treatment. Accordingly, we aimed to evaluate the anti-inflammatory effects of Bacteroidota strains isolated from donors. METHODS: Donors with proven efficacy of fecal microbiota transplantation for ulcerative colitis were selected, and Bacteroidota strains were isolated from their stools. The immune function of Bacteroidota isolates was evaluated through in vitro and in vivo studies. RESULTS: Twenty-four Bacteroidota strains were isolated and identified. Using an in vitro interleukin (IL)-10 induction assay, we identified 4 Bacteroidota strains with remarkable IL-10-induction activity. Of these, an Alistipes putredinis strain exhibited anti-inflammatory effects in a mouse model of colitis induced by sodium dextran sulfate and oxazolone. However, 16S rRNA gene-based sequencing analysis of A. putredinis cultures in the in vivo study revealed unexpected Veillonella strain contamination. A second in vitro study confirmed that the coculture exhibited an even more potent IL-10-inducing activity. Furthermore, the production of A. putredinis-induced IL-10 was likely mediated via toll-like receptor 2 signaling. CONCLUSIONS: This study demonstrated that A. putredinis, a representative Bacteroidota species, exhibits anti-inflammatory effects in vivo and in vitro; however, the effects of other Bacteroidota species remain unexplored. Our fecal microbiota transplantation-based reverse translation approach using promising bacterial species may represent a breakthrough in microbiome drug development for controlling dysbiosis during ulcerative colitis.

We isolated Bacteroidota species from the feces of donors who were effectively cured of UC with fecal microbiota transplantation and proved the anti-inflammatory effects of Bacteroidota species, especially Alistipes putredinis, through cell experiments and in vivo experiments.

Efficacy and safety of filgotinib for ulcerative colitis: A real-world multicenter retrospective study in Japan.

BACKGROUND AND AIMS: While filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, is approved for moderately to severely active ulcerative colitis (UC), real-world studies assessing its short- and long-term efficacy and safety are limited. METHODS: This is a multicenter, retrospective study of UC patients who started filgotinib between March 2022 and September 2023. The primary outcome was clinical remission, defined as a partial Mayo score ≤1 with a rectal bleeding score of 0, or Simple Clinical Colitis Activity Index (SCCAI) ≤2 with a blood-in-stool score of 0. Secondary outcomes included clinical response, corticosteroid-free remission, and endoscopic improvement. Outcomes were assessed at 10, 26, and 58 weeks based on patients with available follow-up. Adverse events were evaluated. RESULTS: We identified 238 UC patients and 54% had prior exposure to biologics/JAK inhibitors. The median baseline partial Mayo score and SCCAI were 5 (IQR 3-6) and 4 (IQR 2-7). Clinical remission rates based on per-protocol analysis at 10, 26, and 58 weeks were 47% (70/149), 55.8% (48/86), and 64.6% (31/48), respectively. At a median follow-up of 28 weeks (IQR 10-54) with a discontinuation rate of 39%, the rates of clinical remission, clinical response, corticosteroid-free remission, and endoscopic improvement were 39.9% (81/203), 54.7% (111/203), and 36.5% (74/203), and 43.5% (10/23), respectively. These rates were comparable between biologic/JAK inhibitor-naïve and -experienced patients. While three patients (1.3%) developed herpes zoster infection, no cases of thrombosis or death were reported. CONCLUSIONS: Real-world data demonstrate favourable clinical and safety outcomes of filgotinib for UC.

[Microvascular Decompression:The Superiority of Transposition].

In this feature article, we underscore the advantages of Transposition over Interposition in the management of trigeminal neuralgia and hemifacial spasm. Interposition, while effective, has raised concerns owing to long-term complications associated with the use of artificial materials, such as Teflon and silicone sponges. Transposition, on the other hand, mitigates these issues, showcasing adaptability to a range of anatomical and pathological conditions and affirming its standing as a safer and more effective treatment alternative. Each technique has distinct applications that are governed by the patient's specific anatomical and pathological needs. While Transposition is emerging as a favored option, Interposition remains relevant in specific cases, underscoring the necessity for a personalized approach to neurovascular decompression. In offering a comprehensive overview, this article is not just an academic exercise, but also a practical resource. A nuanced exploration of these surgical interventions is meant to provide readers with actionable insights, blending the current findings with real-world applicability. The goal is to foster a deeper understanding and aid practitioners in making informed decisions that are finely attuned to each patient's unique needs and conditions, ensuring optimal outcomes, while prioritizing safety and effectiveness.

Retrograde Transcaval Obliteration for Refractory Hepatic Encephalopathy with Multiple Intrahepatic Portosystemic Venous Shunts.

An intrahepatic portosystemic venous shunt (IPSVS) is a rare vascular abnormality, particularly in patients without cirrhosis. An 80-year-old woman without a history of chronic liver disease was admitted to our hospital with hepatic encephalopathy. Computed tomography revealed multiple IPSVSs with two large shunts in segment 6. As conservative therapies were insufficient for treating the symptoms and reducing ammonia levels, retrograde transcaval obliteration was performed. The two large shunts were successfully embolized using detachable coils. Consequently, hyperammonemia and hepatic encephalopathy dramatically improved, and the triphasic wave patterns of the electroencephalogram disappeared. Retrograde transcaval obliteration may be effective for refractory hepatic encephalopathy with IPSVS.

Small Intestinal Arteriovenous Malformation Treated by Double-balloon Endoscopy: A Case Report.

A 42-year-old man was referred to our hospital because of anemia. The patient underwent gastroscopy and colonoscopy, but no bleeding site was detected. Abdominal contrast-enhanced computed tomography (CT) showed vascular dilatation along the wall of the small intestine. Small bowel capsule endoscopy and antegrade double-balloon endoscopy (DBE) were performed, and the patient was diagnosed with a small intestinal arteriovenous malformation (AVM). The AVM was clipped using DBE. After clipping, abdominal contrast-enhanced CT and small bowel angiography revealed the disappearance of the AVM. DBE may be a viable therapeutic option, helping avoid surgery and its associated risks.

Successful Treatment of Steroid-resistant Eosinophilic Gastrointestinal Disease with Mepolizumab.

We experienced a case of treatment-resistant eosinophilic gastrointestinal disease (EGID). The patient, a 46-year-old man, presented with a fever, persistent abdominal pain, and an elevated peripheral eosinophil count. Eosinophil infiltration of the intestinal mucosa was also observed, and EGID was diagnosed. Corticosteroid therapy was initiated, but no improvement was seen. However, after mepolizumab (anti-interleukin 5 antibody) was administered, the patient's disease was controlled. Currently, the indications for mepolizumab are limited to bronchial asthma and paraneoplastic eosinophilic polyangiitis, but the experience herein reported suggests its usefulness in the treatment of EGID.

Isolated Adrenocorticotropic Hormone Deficiency Associated with Atezolizumab and Bevacizumab Administration for Treating Hepatocellular Carcinoma: A Case Series.

Atezolizumab and bevacizumab are currently available as first-line treatments for unresectable hepatocellular carcinoma, but immune-related adverse events are a major concern. We herein report two cases of isolated adrenocorticotropic hormone (ACTH) deficiency. Both patients presented with general fatigue, appetite loss, eosinophilia, and hyponatremia after nine cycles in case 1 and three months after stopping treatment for inflammatory arthritis in case 2. Endocrinological investigations revealed unsatisfactory ACTH and cortisol responses despite the preservation of other anterior pituitary hormones, suggesting isolated ACTH deficiency. As it is rapidly improved by steroid replacement therapy, an early diagnosis and treatment make it possible to resume immunotherapy.

Evaluation of Posterior Ligamentous Complex Injury in Thoracolumbar Burst Fractures: Correlation Analysis of CT and MRI Findings.

The goal of this study is to perform correlation analysis of Computed tomography (CT) and magnetic resonance imaging (MRI) results in posterior ligament complex (PLC) injury and define the morphological traits of thoracolumbar (TL) burst fractures connected to PLC injury. Forty patients with surgically repaired TL burst fractures between January 2013 and December 2020 were retrospectively analyzed. The patients were split into two groups for comparison based on MRI (Group P: patients with a confirmed or suspected PLC injury; Group N: patients with PLC injury denied). The radiographic morphological examination based on CT scans and clinical evaluation was performed and compared between two groups. The thoracolumbar injury classification and severity score (TLICS), the load sharing classification (LSC) scores, and the number of patients with neurological impairments were considerably greater in Group P. Loss of height of the fracture (loss height), local kyphosis of the fracture (local kyphosis), and supraspinous distance were significantly higher in Group P and significantly associated with PLC injuries indicating severe vertebral body destruction and traumatic kyphosis in multivariate logistic analysis [odds ratio: 1.90, 1.06, and 1.13, respectively]. Cutoff value for local kyphosis obtained from the receiver operating characteristic curve was 18.8. If local kyphosis is greater than 18.8 degrees on CT scans, we should take into account the probability of the highly damaged burst fracture associated with PLC injury. In this situation, we should carefully assess MRI to identify the spinal cord injury or spinal cord compression in addition to PLC injury because these instances likely present with neurological abnormalities.

Enterolith Treated with a Combination of Double-Balloon Endoscopy and Cola Dissolution Therapy.

A 71-year-old woman with rheumatoid arthritis who had been taking NSAIDs for many years consulted our hospital for abdominal pain. She was diagnosed with a small bowel obstruction due to an enterolith according to an abdominal CT scan that showed dilation from the enterolith in the small intestine on the oral side. It was considered that the intestinal stone was formed due to stagnation of intestinal contents and had gradually increased in size, resulting in an intestinal obstruction. We performed antegrade double-balloon endoscopy (DBE) to observe and remove the enterolith. We used forceps and a snare to fracture the enterolith. During this attempt, we found a seed in the center of the enterolith. Since the intestinal stone was very hard, cola dissolution therapy was administered from an ileus tube for 1 week. The following week, DBE was performed again, and it was found that the stone had further softened, making attempts at fracture easier. Finally, the enterolith was almost completely fractured. Intestinal stenosis, probably due to ulcers caused by NSAIDs, was found. Small bowel obstruction with an enterolith is rare. In this case, it was considered that the seed could not pass through the stenotic region of the small intestine and the intestinal contents had gradually built up around it. It has been suggested that DBE may be a therapeutic option in cases of an enterolith. Further, cola dissolution therapy has been shown to be useful in treating an enterolith, with the possible explanation that cola undergoes an acid-base reaction with the enterolith. In summary, we report, for the first time, treatment of an enterolith with a combination of DBE and cola dissolution therapy, thereby avoiding surgery and its risks.

Differential diagnosis of ulcerative colitis with increased diarrhea; collagenous colitis or irritable bowel syndrome? A case report.

A 50-year-old man with a 20-year history of left-sided ulcerative colitis (UC) presented to our hospital with sudden onset of watery diarrhea. To this point, he had been treated with mesalazine 2.0 g/day for UC and had maintained remission. We considered that the UC had worsened. We immediately performed surveillance colonoscopy, which revealed a normal mucous membrane. The results of blood laboratory examinations were normal. Histopathology of colonic biopsies revealed new-onset collagenous colitis (CC), with a thickened subepithelial collagen band (SECB) and inactive UC. We herein report the importance of random colonic biopsies to diagnose CC even when the endoscopic appearance of the colon is normal in patients with inflammatory bowel disease with worsened diarrhea.

Early Clinical Remission Is a Predictor of Long-Term Remission with the Use of Vedolizumab for Ulcerative Colitis.

Vedolizumab (VDZ) is an α4ß7 integrin-antibody used to manage refractory ulcerative colitis (UC). This retrospective multicenter study aimed to identify predictors of efficacy or the time points when evaluation of VDZ therapy for UC would be most useful. We compiled data on 87 patients with moderate to severe active UC that was treated with VDZ. Overall clinical remission (CR) rates at 6 weeks and 52 weeks after VDZ administration were 44.4% (bio-naïve 44.2%, bio-failure 44.8%) and 52.8% (bio-naïve 53.5%, bio-failure 51.7%) respectively. Also, 83.3% (bio-naïve 81.3%, bio-failure 85.7%) of patients achieved mucosal healing at week 52. Among patients with a CR at week 52, 73.3% had a CR at week 6. In contrast, of patients who discontinued VDZ, 82.4% had not reached a CR at week 6. Our study demonstrated that VDZ was effective in a large percentage of UC patients, with a high mucosal healing rate even after prior biological exposures. This suggests that VDZ can be a treatment option even in bio-failure cases. Additionally, it was considered that early CR can predict long-term remission and that week 6 can be a helpful evaluation point for treatment decisions when using VDZ for UC.

Linked color imaging improves visibility of colorectal serrated lesion by high color contrast to surrounding mucosa.

OBJECTIVES: This study aimed to objectively evaluate the efficacy of linked color imaging (LCI) in diagnosing colorectal serrated lesions by utilizing visibility scores and color differences. METHODS: We examined 89 serrated lesions, including 36 hyperplastic polyps (HPs), 47 sessile serrated lesions (SSLs), and six traditional serrated adenomas (TSAs). Visibility changes were scored by six endoscopists as follows: 4, excellent; 3, good; 2, fair; and 1, poor. Furthermore, images obtained by white-light imaging (WLI) or LCI were assessed using the CIELAB color space in the lesion and adjacent mucosa. We calculated the mean color values (L*, a*, and b*) measured at five regions of interest of the sample lesion and surrounding mucosa and derived the color difference (ΔE*). RESULTS: The visibility scores of both HPs and SSLs in LCI were significantly higher than that in WLI (HPs, 3.67/2.89, P < 0.001; SSLs, 3.07/2.36, P < 0.001). Furthermore, SSLs showed a significantly higher L* value and significantly lower a* and b* values in LCI than the adjacent mucosae (L*, 61.76/58.23, P = 0.016; a*, 14.91/17.58, P = 0.019; b*, 20.42/24.21, P = 0.007), while WLI produced no significant difference in any color value. A similar trend was apparent in HPs. In all serrated groups, LCI revealed significantly greater ΔE* values between the lesion and adjacent mucosa than WLI (HPs, 11.54/6.12; SSLs, 13.43/7.67; TSAs, 35.00/22.48). CONCLUSION: Linked color imaging showed higher color contrast between serrated lesions and the surrounding mucosae compared with WLI, indicating improved visibility of colorectal serrated lesion using LCI.

A Randomized Placebo-Controlled Trial of Combination Therapy With Post-triple-antibiotic-therapy Fecal Microbiota Transplantation and Alginate for Ulcerative Colitis: Protocol.

Background: Fecal microbiota transplantation (FMT) has been widely performed for ulcerative colitis (UC) treatment at the clinical trial stage. Previous reports have used multiple FMT methods to enhance the colonization of healthy donor microbiota in the recipient's intestines. FMT following triple antibiotic therapy with amoxicillin, fosfomycin, and metronidazole (A-FMT) is not only effective but also requires only one FMT, which improves dysbiosis caused by reduced Bacteroidetes diversity in patients with UC. Alginate and its derivatives have the potential to induce the growth of intestinal bacteria including Bacteroides members and produce short-chain fatty acids (SCFAs), which are beneficial in regulating overactive autoimmunity. Our trial aims to investigate whether post-intervention with alginate, which can improve the intestinal environment, will enhance the therapeutic effect of A-FMT in UC and increase the long-term remission rate. Methods and Analysis: This trial is a double-blinded, randomized, placebo-controlled, parallel assignment trial. Patients with UC and fecal donation candidates will undergo strict screening before being involved in the trial. Eligible patients are randomly divided into two groups: one group will drink one bottle of alginate twice a day for 8 consecutive weeks after A-FMT, while the other group will take a placebo instead of the alginate drink. The primary endpoints are the changes in the Total Mayo Score at 8 weeks after study initiation and A-FMT from baseline. The secondary endpoint is the comparison of clinical features, microbiota, and metabolomic analysis before and after 8 weeks of study food intake. Changes at 6, 12, 18, and 24 months after A-FMT will be assessed. Finally, a subpopulation analysis of the relationship between patients and donors is an exploratory endpoint. Discussion: The FMT post-treatment used in this study is an oral alginate drink that is easily accepted by patients. If the regimen achieves the desired results, it can further improve the A-FMT regimen and provide evidence for clinical practice guidelines for UC. Clinical Trial Registration: https://jrct.niph.go.jp/latest-detail/jRCTs031200103, identifier: jRCTs031200103.

Efficacy of cytapheresis for induction therapy and extra-intestinal skin manifestations of ulcerative colitis.

INTRODUCTION: In recent years, the prevalence of inflammatory bowel diseases has been increasing in Japan due to the westernization of lifestyles. Many patients have been reported to have extra-intestinal manifestations (EIMs) at least once. Skin lesions occur with a high degree of frequency among EIMs, with erythema nodosum (EN) and pyoderma gangrenosum (PG) the main complications. Cytapheresis is again attracting attention as a treatment with few side effects. METHODS: We investigated the therapeutic effect of cytapheresis on ulcerative colitis (UC) and cutaneous EIMs. Between 2008 and 2021, 240 patients with active UC had induction therapy by cytapheresis at our hospital. RESULTS: Remission and response rates were 50.0% and 67.5%, respectively. Apheresis was performed on seven patients with PG and five patients with EN with a good response. Serious adverse events were not observed. CONCLUSION: This retrospective assessment of efficacy showed that EN and PG responded favorably to cytapheresis.

Donor Screening Revisions of Fecal Microbiota Transplantation in Patients with Ulcerative Colitis.

Fecal microbiota transplantation (FMT) has been recognized as a promising treatment for dysbiosis-related diseases. Since 2014, FMT has been utilized to treat ulcerative colitis (UC) in our clinical studies and has shown efficacy and safety. As donor screening (DS) is the primary step to ensure the safety of FMT, we report our experience with DS and present the screening results to improve the prospective DS criteria and provide references for future studies. The donor candidates were screened according to the DS criteria. The first DS criteria were proposed in June 2014 and revised substantially in May 2018. We further sorted the screening results and costs of laboratory tests. From June 2014 to April 2018, the DS eligibility rate was 50%. The total laboratory testing cost for each candidate was JPY 17,580/USD 160.21. From May 2018 to September 2021, the DS eligibility rate was 25.6%. The total laboratory testing cost for each candidate was JPY 40,740/USD 371.36. The reduction in donor eligibility rates due to more stringent criteria should be considered for cost and safety. Studies must consider the latest updates and make timely modifications in the DS criteria to ensure patient safety.

Treating Low-Grade Myxofibrosarcoma With Stereotactic Body Radiation Therapy Using CyberKnife®.

Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas. Low-grade MFS has a high local recurrence rate, similar to that of high-grade MFS. Hence, appropriate adjuvant therapy is required to control low-grade MFS. In this report, we present a case in which recurrent low-grade MFS was successfully treated with stereotactic body radiation therapy (SBRT) using CyberKnife® (CK) (Accuray Incorporated, Sunnyvale, CA). A 76-year-old man underwent SBRT using CK for recurrent low-grade MFS in the right posterior chest wall after undergoing resection and skin grafting four and three times, respectively. We planned CK treatment separately for each in two parts. For the lesion on the scapula side, the target volume was 109 cm3 and the total prescribed dose was 34.6 Gy, while the lesion on the spinal side had a target volume of 72 cm3 and a total prescribed dose of 36 Gy, both in five fractions. Each SBRT was performed on alternate days in a span of 14 days. The tumors gradually reduced in size with tolerable levels of toxicity. SBRT using CK could be a safe and effective adjuvant therapy for low-grade MFS.

Extraction of water-soluble polysaccharides from kidney beans and examination of their protein dispersion and stabilization properties under acidic conditions.

The extraction conditions of kidney bean water-soluble polysaccharides (SKPSs) from kidney bean fibers were examined. The factors such as temperature, pH, and time were combined to derive the conditions for obtaining high yields of high molecular mass polysaccharides. The optimal extraction temperature, time, and pH were 120 °C, 30 min, and 9, respectively. Under these conditions, the yield of SKPS (SKPS9) obtained was as high as 26.4%. The weight average molecular mass of SKPS9 measured using size exclusion chromatography equipped with a multi-angle laser light scattering detector was 2,530 kg/mole. The main constituent sugars of SKPS9 were arabinose (67.2%) and galacturonic acid (15.6%). SKPS9 carbohydrate molecules observed using a scanning probe microscope showed the mixed structures of a multi-branched structure, whose sugar chains extended outward from the center to the periphery of the molecule, and a little-branched straight chain structure. SKPS9 had protein dispersing and stabilizing properties under acidic conditions. In the acidified milk system containing 3% non-fat milk solids, 0.4% SKPS9 was able to maintain a mono-modal distribution of fine protein particles in pH level ranging from 3.8 to 4.4. This work suggests the potential for the creation of a value added ingredient from kidney bean.

Usefulness of arterial spin labeling in the evaluation for dural arteriovenous fistula of the craniocervical junction.

In the diagnosis of an intracranial dural arteriovenous fistula (DAVF), arterial spin labeling (ASL), a sequence of magnetic resonance imaging (MRI) to depict high-blood-flow intracranial lesions, has been reported as a useful and noninvasive tool, not only to predict the presence of cortical venous drainage and draining veins, but also to confirm persistent obliteration after treatment. However, such utility of ASL has not been reported in DAVF of the craniocervical junction (CCJDAVF) because of the rarity of this disease and uncertainty in the acquisition of precise images. We report a case of CCJDAVF presenting with myelopathy. Preoperative ASL images showed an abnormal high-intensity signal in the craniocervical junction, consistent with the anterior spinal vein and draining veins, which were also identified by digital subtraction angiography. After successful surgical treatment for the disease, MRI and 4-dimensional computed tomography angiography (4DCTA) confirmed complete disappearance of CCJDAVF. The ASL images also showed no abnormal intensity signal. The patient was followed-up using ASL, and no recurrence of high-intensity signal was observed. As repetitive image examination is mandatory in the follow-up of a patient with DAVF to exclude recurrence, ASL is highly beneficial because of the unnecessity of an exogenous contrast medium and high credibility to depict the disease. The craniocervical junction may be out of the field of view in routine MRI. Special attention must be paid to setting the field of view and post labeling delay (PLD) to obtain precise images of ASL in CCJDAVF.