Anti-integrin αvß6 autoantibodies are a potential biomarker for ulcerative colitis-like immune checkpoint inhibitor-induced colitis.

BACKGROUND: No specific biomarker for immune checkpoint inhibitor (ICI)-induced colitis has been established. Previously, we identified anti-integrin αvß6 autoantibodies in >90% of patients with ulcerative colitis (UC). Given that a subset of ICI-induced colitis is similar to UC, we aimed to clarify the relationship between such autoantibodies and ICI-induced colitis. METHODS: Serum anti-integrin αvß6 autoantibody levels were compared between 26 patients with ICI-induced colitis and 157 controls. Endoscopic images of ICI-induced colitis were centrally reviewed. Characteristics of anti-integrin αvß6 autoantibodies in the ICI-induced colitis patients were compared with those of UC patients. RESULTS: Anti-integrin αvß6 autoantibodies were found in 8/26 (30.8%) patients with ICI-induced colitis and 3/157 (1.9%) controls (P < 0.001). Patients with anti-integrin αvß6 autoantibodies had significantly more typical UC endoscopic features than those without the autoantibodies (P < 0.001). Anti-integrin αvß6 autoantibodies in ICI-induced colitis patients were associated with grade ≥3 colitis (P = 0.001) and steroid resistance (P = 0.005). Anti-integrin αvß6 autoantibody titers correlated with ICI-induced colitis disease activity. Anti-integrin αvß6 autoantibodies of ICI-induced colitis exhibited similar characteristics to those of UC. CONCLUSIONS: Anti-integrin αvß6 autoantibodies may serve as potential biomarkers for the diagnosis, classification, risk management, and monitoring the disease activity, of ICI-induced colitis.

Designing a muon scattering scanner for nuclear debris measurement.

Removal of fuel debris is planned to start at Unit 2 of the Fukushima Daiichi Nuclear Power Plant. During the removal, it is desirable to distinguish fuel debris from radioactive wastes and to sort the fuel debris accordingly to the amounts of nuclear material contained. Muon scattering tomography invented at Los Alamos in the early 2000s is highly sensitivity to high-atomic-number materials such as uranium. A muon scanner to sort the debris is designed and currently in production. One of the challenges is to operate the muon scanner in the presence of high γ-ray radiations from the debris: muon-event-identification electronics and a muon-tracking algorithm in the presence of high γ-ray radiations were developed.

A Prospective Randomized Controlled Trial of the Effect of Maintenance of Continuous Cuff Pressures (20 cmH2O vs 30 cmH2O) on Postoperative Airway Symptoms in Laparoscopic Surgeries.

INTRODUCTION: Recently, laparoscopic surgery has been used in many fields of surgery. It has been reported that cuff pressure becomes high during laparoscopic surgery. Increased cuff pressure may cause postoperative sore throat and hoarseness. Considering previous reports, we hypothesized that maintenance of a fixed low cuff pressure during laparoscopic surgery might be associated with low grades of postoperative sore throat and hoarseness. METHODS: The participants were 100 patients between 20 and 80 years of age who were scheduled to undergo laparoscopic surgery lasting over 2 hours. Patients were randomly allocated to two groups with endotracheal tube cuff pressures fixed at 20 cmH2O (low-pressure group; LPG) and 30 cmH2O (high-pressure group; HPG). We evaluated mainly sore throat and hoarseness on postoperative day 1 using a visual analog scale (VAS; 0-10 cm). Statistical comparisons of values were performed using the unpaired t-test, Mann-Whitney U-test, and chi-square test with values of p < 0.05 considered statistically significant. RESULTS: There were no significant differences in background characteristics between the two groups. Median postoperative scores for the LPG and HPG were 1 (interquartile range, 0-3) and 0 (0-2; p = 0.560) for sore throat and 2 (0-4) and 1 (0-3; p = 0.311) for hoarseness, respectively, and the differences were not significant. CONCLUSION: The effects of maintenance of a fixed low cuff pressure and a fixed high cuff pressure on the degrees of postoperative sore throat and hoarseness after laparoscopic surgery were the same and the grades were low.

Single Nucleotide Polymorphisms of the MEFV Gene E148Q Are Highly Associated With Disease Phenotype in Crohn's Disease.

BACKGROUND: Single nucleotide polymorphisms (SNPs) of the MEFV gene may modify inflammatory bowel disease (IBD) activity. The prevalence of MEFV gene SNPs in IBD patients and their involvement in IBD pathophysiology remains unclear. METHODS: We analyzed 12 MEFV gene SNPs in peripheral leukocytes of Japanese IBD patients (Crohn's disease [CD]: 69 patients, ulcerative colitis: 32 patients) by polymerase chain reaction using next-generation DNA sequencing and evaluated their prevalence and association with the disease characteristics. Inflammasome activity and mature interleukin (IL)-1ß and IL-18 production were evaluated in peripheral blood mononuclear cells obtained from CD patients stimulated with lipopolysaccharides and adenosine triphosphate, and compared between those with and without the E148Q SNP. COL1A1 and HSP47 gene expression was analyzed in CCD-18Co cells costimulated with IL-1ß and other inflammatory cytokines. RESULTS: The prevalence of MEFV gene SNPs in IBD patients was similar to that in the human gene database. E148Q was the most common SNP. Compared with CD patients without E148Q, those with E148Q had a significantly greater frequency of the stricture phenotype, and their peripheral blood mononuclear cells exhibited significantly higher IL-1ß and IL-18 levels and higher caspase-1 activity. IL-1ß and IL-17A synergistically increased COL1A1 and HSP47 gene expression. CONCLUSIONS: MEFV gene SNPs, including E148Q, modify the behavior of CD. IL-1ß and IL-18 are produced through enhanced caspase-1 activity in monocytes of CD patients with E148Q. IL-1ß promotes gene expression of fibrosis-related genes by cooperating with IL-17A in myofibroblasts. Therefore, E148Q might be a disease-modifying gene associated with the fibrostenosis phenotype in CD patients.

MEFV gene single nucleotide polymorphisms, including E148Q, modify the behavior of Crohn's disease to form stenosis. Interleukin-1ß is produced through enhanced caspase-1 activity in monocytes of Crohn's disease patients with E148Q, and promotes gene expression of fibrosis-related genes by cooperating with interleukin-17A in myofibroblasts.

Multicenter prospective registration study of efficacy and safety of capsule endoscopy in Crohn's disease in Japan (SPREAD-J study).

BACKGROUND: Evidence of small-bowel capsule endoscopy (SBCE) for evaluating lesions in Crohn's disease (CD) is lacking. We aimed to clarify the effectiveness and safety of SBCE in a large sample of patients with CD. METHODS: This multicenter prospective registration study recorded the clinical information and SBCE results of patients with definitive CD (d-CD) or suspected CD (s-CD). The primary outcomes were the rates of successful assessment of disease activity using SBCE, definitive diagnosis of CD, and adverse events. Secondary outcomes were the assessment of SBCE findings in patients with d-CD and s-CD and factors affecting SBCE incompletion and retention; and tertiary outcomes included the association between clinical disease activity or blood examination, endoscopic disease activity, ileal CD, and the questionnaire assessment of patient acceptance of SBCE. RESULTS: Of 544 patients analyzed, 541 underwent SBCE with 7 (1.3%) retention cases. Of 468 patients with d-CD, 97.6% could be evaluated for endoscopic activity. Of 76 patients with s-CD, 15.8% were diagnosed with 'confirmed CD'. CD lesions were more frequently observed in the ileum and were only seen in the jejunum in 3.4% of the patients. Male sex and stenosis were risk factors for incomplete SBCE, and high C-reactive protein levels and stenosis were risk factors for capsule retention. In L1 (Montreal classification) patients, clinical remission was associated with endoscopic remission but showed low specificity and accuracy. The answers to the acceptability questionnaire showed the minimal invasiveness and tolerability of SBCE. CONCLUSION: SBCE is practical and safe in patients with CD.

A Patient with Class III Obesity and a Body Mass Index of 70.1 kg/m² Requiring Pulmonary Artery Catheterization to Confirm the Diagnosis of Pulmonary Hypertension.

BACKGROUND Intensive care management of patients with morbid obesity has been linked to a higher mortality rate than that of the normal population and can be challenging. Obesity is a recognized risk factor for pulmonary hypertension, but it can prevent cardiac imaging. This report presents the case of a 28-year-old man with class III (morbid) obesity, a body mass index (BMI) of 70.1 kg/m², and heart failure, requiring pulmonary artery catheterization (PAC) to confirm the diagnosis of pulmonary hypertension. CASE REPORT A 28-year-old male patient with a a body mass index (BMI) of 70.1 kg/m² was admitted to the Intensive Care Unit (ICU) for the management of respiratory and cardiac failure. The patient had class III obesity (BMI >50 kg/m²) and heart failure. Due to the difficulties in evaluating hemodynamic status via echocardiography, a pulmonary artery catheter (PAC) was placed, revealing a mean pulmonary artery pressure of 49 mmHg, and a diagnosis of pulmonary hypertension was made. The alveolar partial pressures of oxygen and carbon dioxide were optimized by ventilatory management to reduce pulmonary vascular resistance. The patient was extubated on day 23 and was discharged from the ICU on day 28. CONCLUSIONS Pulmonary hypertension should be considered in the evaluation of obese patients. Using a PAC during the intensive care management of a patient with obesity could aid in the diagnosis of pulmonary hypertension as well as cardiac dysfunction, determine treatment strategies, and evaluate hemodynamic responses to various therapies.

The association between antigenemia, histology with immunohistochemistry, and mucosal PCR in the diagnosis of ulcerative colitis with concomitant human cytomegalovirus infection.

BACKGROUND: Human cytomegalovirus (HCMV) colitis can be involved in active ulcerative colitis (UC) in patients refractory to steroid and immunosuppressive drugs. Histological examination with colonic biopsy specimens and antigenemia assays are the standard tests for diagnosing HCMV enterocolitis, and we have previously reported the usefulness of mucosal polymerase chain reaction (PCR) methods. However, the associations among histopathological tests, antigenemia assays, and mucosal PCR are unknown. METHODS: We retrospectively analyzed 82 UC patients who underwent mucosal biopsy from inflamed colonic tissues for histological evaluation and mucosal PCR to detect HCMV. We analyzed the relationships between the HCMV-DNA copy number in colonic mucosa and other HCMV tests. RESULTS: In total, 131 HCMV mucosal PCR tests from 82 UC patients were positive. The HCMV-DNA copy number was significantly higher in patients with positive immunohistochemistry (IHC) (p < 0.01) and was correlated with the number of positive cells for the antigenemia (C7-HRP, p < 0.01; C10/11, p < 0.01). Receiver operating characteristic curve analysis confirmed 1300 copies/µg of HCMV-DNA as the best diagnostic cut-off value to predict positive results of antigenemia (area under the curve = 0.80, 95% CI 0.68-0.93). HCMV-DNA copy number also correlated with the total UCEIS score (p = 0.013) and the bleeding score (p = 0.014). For each individual patient, a positive correlation between the change in total UCEIS score and HCMV-DNA copy number was observed (p = 0.040). CONCLUSION: The antigenemia assay and histopathological test with IHC were significantly associated with the HCMV-DNA copy number in colonic tissues. Moreover, endoscopic examination with the UCEIS can help diagnose the HCMV colitis in UC patients.

Genetic characterization of 1210 Japanese pedigrees with inherited retinal diseases by whole-exome sequencing.

Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528G>A). In addition to the two known EYS founder mutations (c.4957dupA and c.8805C>G) of arRP, we observed a frequent RP1 variant (c.5797C>T) in patients with arMD/CORD.

Selection of the right inferior phrenic artery using a dual-lumen microcatheter in transarterial chemoembolization for hepatocellular carcinoma.

An 88-year-old woman with a history of multiple hepatocellular carcinomas (HCCs) presented with a new HCC in segment seven of the liver. We decided to perform transarterial chemoembolization for HCC. During treatment, the HCC was supplied by the right inferior phrenic artery (IPA), which originated from the proximal part of the left gastric artery with a steep bifurcation angle. Due to the very short distance between the origins of the left gastric artery and right IPA, the microguidewire and microcatheter were unstable in the left gastric artery and easily prolapsed into the celiac artery. Although different types of microcatheters were used, the right IPA could not be selected. Therefore, we used a dual-lumen microcatheter (DLM) to select the right IPA. The DLM stabilized the microguidewire in the left gastric artery, and the right IPA was successfully selected. Subsequently, transarterial chemoembolization was administered using a branch of the right IPA. Given this experience, we will consider using a DLM as an alternative method for selecting an abdominal artery when other techniques are unsuccessful.

Pancreatic metastasis of malignant melanoma presenting as a tumor occluding the main pancreatic duct.

Metastasis to the pancreas is rare, especially for malignant melanoma. In these scarce cases, tumors normally present in the parenchyma of the pancreas. A 70-year-old woman was referred to our hospital for an asymptomatic pancreatic tumor detected by contrast-enhanced computed tomography (CE-CT). She had undergone a pneumonectomy for primary malignant melanoma (MM) of the lung approximately 3 years prior and was receiving nivolumab for recurrent intrapulmonary metastasis. CE-CT revealed a hypo-vascular lesion occluding the main pancreatic duct (MPD) which was consequently dilated. On magnetic resonance imaging, the MPD lesion had high signal intensity on T1-weighted and diffusion-weighted images. Contrast-enhanced endoscopic ultrasonography revealed that the low echoic tumor had heterogenous enhancement in the early phase. Endoscopic retrograde pancreatography (ERP) was performed for evaluation of tumor area and histological diagnosis. A contrast agent defected lesion was observed in the dilated MPD from the pancreas body to tail suggesting the tumor totally occluded the MPD. Biopsy was performed and the specimens obtained from the defect lesion were black in color. Histopathological examination of the black specimens revealed substantial growth of tumor cells with eosinophilic cytoplasm and unequal nuclei size. The tumor cells had a brownish pigmentation of melanin. From these findings, the tumor was diagnosed as pancreatic metastasis of MM. The patient underwent chemotherapy with ipilimumab and nivolumab. The final diagnosis was pancreatic metastasis of MM occurring as a tumor occluding the MPD. ERP was useful for histological diagnosis and could be useful for future cases.

Case Report: Occurrence of Thyroid Storm in a Young Patient With Recurrent Diabetic Ketoacidosis.

Background: Thyroid storm (TS) is a fatal disease that leads to multiple organ failure and requires prompt diagnosis. Diabetic ketoacidosis (DKA) is a trigger for thyroid crisis. However, TS and DKA rarely occur simultaneously. Moreover, owing to the rarity of the co-occurrence, the clinical course remains unclear. In this study, we present a case of TS that developed during the follow-up for repeated DKA in a young patient. Case Presentation: A 25-year-old man with a history of recurrent DKA was brought to the emergency room frequently with similar symptoms. DKA treatment was initiated, but his tachycardia and disturbance of consciousness did not improve. Further examination of the patient revealed a Burch-Wartofsky Point Scale score of 80 points, consistent with the Japan Thyroid Association criteria. Therefore, DKA coexisting with TS was diagnosed. Antithyroid medication, inorganic iodine, and corticosteroids were then started as treatment for TS, and ß-blockers were administered to manage tachycardia. With these treatments, the patient's health improved and he recovered. Conclusions: In severe cases of recurrent DKA, the presence of TS should be considered, and early treatment should be initiated before the patient's condition worsens.

A case of intestinal amoebiasis mimicking intestinal Behçet's disease.

Intestinal amoebiasis is caused by Entamoeba histolytica (E. histolytica) and is characterised by cecal lesions, multiple lesions, aphthae, and multiple exudative erosions. Intestinal Behçet's disease (BD) is a chronic inflammatory disorder that is characterised by multiple ulcers. Although the aetiologies of these two bowel diseases are unrelated, they are difficult to distinguish because they present similarly with inflammation and ulcers, especially if evidence of specific pathogens is not detected. Herein, we report a case of intestinal amoebiasis in a patient with BD. The patient underwent colonoscopy four times before intestinal amoebiasis was diagnosed. As intestinal BD was initially suspected, she received high-dose glucocorticoid therapy, which exacerbated her condition. Following exacerbation, she underwent colonoscopy, and E. histolytica was revealed. Deliberate care should be taken to distinguish between intestinal amoebiasis and intestinal BD, as the appropriate treatments for these diseases are entirely different.

[Acute promyelocytic leukemia complicated with central nervous system involvement successfully treated with all-trans retinoic acid via nasogastric tube].

At initial diagnosis, central nervous system (CNS) involvement in acute promyelocytic leukemia (APL) is rare. Here, we report a case of newly diagnosed APL with CNS involvement that was successfully treated with all-trans retinoic acid (ATRA)-combined chemotherapy. A 64-year-old woman was referred to our hospital to evaluate a bleeding tendency, and she was diagnosed with APL. Induction chemotherapy with ATRA via a nasogastric tube was initiated under mechanical ventilation because of respiratory failure and disturbance of consciousness. Although her respiratory condition improved a few days after initiating treatment, the disturbance of consciousness remained. Brain magnetic resonance imaging showed mixed signals of tumor infiltration and acute cerebral infarction with a focus on the right cerebellum. The patient was diagnosed with CNS involvement of APL and acute cerebral infarction. Three months after the initiation of induction therapy, her consciousness improved along with the reduction in CNS involvement, and complete molecular remission was achieved. Thus, patients with APL can have CNS involvement at initial diagnosis. Administering ATRA via nasogastric tube can be a good therapeutic option in patients with difficulty swallowing due to disturbance of consciousness.

Sudden cardiac arrest associated with myxedema coma due to undiagnosed hypothyroidism: a case report.

BACKGROUND: Myxedema coma, which occurs due to hypothyroidism, is a rare and life-threatening condition. Some patients have hemodynamic dysfunction, which consequently leads to cardiac arrest. The rarity of this condition makes it difficult to determine the cause of cardiac arrest. It is important to diagnose myxedema coma based on clinical findings, including physical examination and laboratory parameters. We present a case of undiagnosed and untreated hypothyroidism that initially caused myxedema coma and then led to cardiac arrest. CASE PRESENTATION: A 56-year-old woman who had no medical history was transferred to our hospital for the management of return of spontaneous circulation due to sudden cardiac arrest. Findings of laboratory tests revealed that she had hypothyroidism. On physical examination, she was found to have a puffy face, thin eyebrows, and severe systemic non-pitting edema. Therefore, the patient was clinically diagnosed with myxedema coma, which was the cause of cardiac arrest. She was treated with thyroid hormone and hydrocortisone, resulting in improvement in her general condition, except for the neurological dysfunction. CONCLUSIONS: This case suggests that myxedema coma is caused by undiagnosed and untreated hypothyroidism, leading to sudden cardiac arrest. Our findings are useful in the differential diagnosis of hypothyroidism based on characteristic physical examination findings. Clinicians should be aware of the differential diagnosis of myxedema coma based on findings from physical examination and laboratory testing of thyroid function, and the treatment should be started immediately.