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Lymphoproliferative disorders are rare complications in patients with autoimmune diseases who are receiving immunosuppressive therapy. This case report describes a 74-year-old man with diffuse cutaneous systemic sclerosis, anti-RNA polymerase III antibodies, and interstitial pneumonia. The patient's condition initially improved with prednisolone and intravenous cyclophosphamide, followed by maintenance therapy with azathioprine, nintedanib, and macitentan for pulmonary hypertension. Thirty months after initiating AZA, the patient developed nodules and ulcers in the left lower jaw and philtrum. Skin biopsy confirmed diffuse large B-cell lymphoma. Discontinuation of azathioprine led to the resolution of the ulcers, and no other lesions were found. This case highlights the risk of iatrogenic immunodeficiency-associated lymphoproliferative disorders in patients with systemic sclerosis, particularly in those with anti-RNA polymerase III antibodies, who are known to have an increased risk of malignancy. Although methotrexate-associated lymphoproliferative disorders are well documented in patients with rheumatoid arthritis, this is the first reported case of azathioprine-associated lymphoproliferative disorder in systemic sclerosis. These findings emphasise the importance of close monitoring of malignancies, including lymphoproliferative disorders, in patients with systemic sclerosis undergoing immunosuppressive therapy., (© Japan College of Rheumatology 2025. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Currently, immune checkpoint inhibitors (ICIs) are the standard treatment for malignant pleural mesothelioma (MPM). The characteristic responses to ICI treatment include pseudoprogression (PP) and hyperprogressive disease (HPD), which require attention. Reports on PP of MPM are rare. We herein report a 59-year-old woman with MPM whose pleural lesions rapidly increased in size after initiating nivolumab treatment. This was initially judged as HPD but was subsequently diagnosed as PP owing to a marked reduction in tumor size. This case highlights the importance and difficulty of differentiating between PP and true progression, including HPD, during treatment of MPM with ICIs.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are highly effective against EGFR-mutant non-small-cell lung carcinoma but can cause serious adverse events, such as interstitial lung disease (ILD). Treatment strategies for osimertinib-induced ILD are not well established. Cytotoxic anticancer drugs are considered first, although several cases of successful rechallenge with EGFR-TKIs have been reported. We herein report a 67-year-old woman with symptomatic osimertinib-induced ILD who was switched to afatinib and later rechallenged with osimertinib and corticosteroids. Neither treatment resulted in ILD relapse, suggesting that these may be viable treatment options when alternative treatments are limited.

A 61-year-old woman, hospitalized for a persistent cough and dyspnea, had no history of bronchial asthma, but was undergoing chemotherapy for methotrexate-related lymphoproliferative disorder due to rheumatoid arthritis. Her peripheral blood eosinophil count was significantly increased, and chest CT revealed left lower lobe atelectasis and high-attenuation mucus. Bronchoscopy revealed mucous plugs and pathological examination revealed numerous eosinophils and filamentous fungi. Allergic bronchopulmonary mycosis (ABPM) caused by Scedosporium apiospermum was diagnosed using culture and genetic analyses. Treatment with corticosteroids and antifungal drugs led to improvement. ABPM caused by S. apiospermum is extremely rare, emphasizing the importance of species identification., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors.)

Background: No comprehensive analysis of the pulmonary sequelae of coronavirus disease 2019 (COVID-19) in Japan based on respiratory function tests and chest computed tomography (CT) has been reported. We evaluated post-COVID-19 conditions, especially focusing on pulmonary sequelae assessed by pulmonary function tests and chest CT., Methods: For this prospective cohort study, we enrolled 1069 patients who presented pneumonia at the time of admission in 55 hospitals from February 2020 to September 2021. Disease severity was classified as moderateⅠ, moderate II, and severe, defined primarily according to the degree of respiratory failure. The data on post-COVID-19 conditions over 12 months, pulmonary function, and chest CT findings at 3 months were evaluated in this study. Additionally, the impact of COVID-19 severity on pulmonary sequelae, such as impaired diffusion capacity, restrictive pattern, and CT abnormalities, was also evaluated., Results: The most frequently reported post-COVID-19 conditions at 3 months after COVID-19 were muscle weakness, dyspnea, and fatigue (48.4%, 29.0%, and 24.7%, respectively). The frequency of symptoms gradually decreased over subsequent months. In pulmonary function tests at 3 months, the incidence of impaired diffusion capacity and restrictive pattern increased depending on disease severity. There also were differences in the presence of chest CT abnormalities at the 3 months, which was markedly correlated with the severity., Conclusion: We reported a comprehensive analysis of post-COVID-19 condition, pulmonary function, and chest CT abnormalities in Japanese patients with COVID-19. The findings of this study will serve as valuable reference data for future post-COVID-19 condition research in Japan., Competing Interests: Declaration of Competing interest The authors have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Constipation causes substantial morbidity worldwide. Methods: This survey assessed constipation-related factors in Japan using the Japanese version of the Irritable Bowel Syndrome Quality of Life (IBS-QOL-J) instrument. We also examined the relationship among laxative type, Bristol Stool Form Scale (BSFS) scores, and treatment cost. Finally, we examined differences in satisfaction scores according to laxative type, treatment type, treatment cost, and BSFS score. Results: IBS-QOL-J was higher among those taking salt and/or irritation laxatives. Those paying >JPY 5000 (USD 50.00) had the lowest IBS-QOL-J. IBS-QOL-J was significantly lower among those with a BSFS score of 1 or 2 (severe constipation). Conclusions: This study's findings suggest that a variety of factors, including treatment type and cost, are associated with defecation satisfaction. Those who had hard stools, used multiple laxatives, or spent more on treatment were less satisfied. Future strategies should target therapies that do not require multiple laxatives with lower treatment costs. Adequate defecation with a small number of appropriate laxatives at minimal cost appears to improve defecation satisfaction. It is desirable to identify appropriate laxatives and improve dietary habits and exercise routines. It is also necessary to stop blindly increasing laxative usage and properly diagnose constipation disorders such as anatomical abnormalities other than functional constipation.

Background: Tocotrienols exhibit antioxidant and anti-inflammatory activities. RhoA, a small GTPase protein, plays a crucial role in regulating contractility in airway smooth muscle (ASM). Previous studies have demonstrated that γ-tocotrienols reduce ASM proliferation and migration by inhibiting the activation of RhoA. In this present study, we investigate the effect of another vitamin E isoform, β-tocotrienols, on human ASM cell proliferation and migration stimulated by platelet-derived growth factor-BB (PDGF-BB)., Methods: Human ASM cells were pre-treated with β-tocotrienol prior to being stimulated with PDGF-BB to induce ASM cell proliferation and migration. The proliferation and migration of PDGF-BB-induced human ASM cells were assessed using colorimetric and transwell migration assays. The intracellular ROS assay kit was employed to quantify reactive oxygen species (ROS) in human ASM cells. Additionally, we explored the effect of β-tocotrienols on the signaling pathways involved in PDGF-BB-induced ASM proliferation and migration., Results: β-tocotrienol inhibited PDGF-BB-induced ASM cell proliferation and migration by reducing RhoA activation and ROS production. However, in this present study, β-tocotrienol did not affect the signaling pathways associated with cyclin D1, phosphorylated Akt1, and ERK1/2., Conclusions: In conclusion, the inhibition of RhoA activation and ROS production by β-tocotrienol, resulting in the reduction in human ASM proliferation and migration, suggests its potential as a treatment for asthma airway remodeling.

Pembrolizumab is an anti-programmed cell death-1 (PD-1) antibody used to treat various cancer types. Treatments with such immune checkpoint inhibitors cause immune-related adverse events. However, airway inflammation caused by immune-related adverse events has rarely been reported. A 54-year-old woman with endometrial cancer experienced asthma exacerbation, and increased blood eosinophil counts 3 months after pembrolizumab administration. Although asthma exacerbation improved, the resumption of pembrolizumab caused the recurrence of dry cough and hypereosinophilia. The discontinuation of pembrolizumab improved her symptoms. Serum interleukin-5 levels increased during pembrolizumab treatment but decreased upon discontinuation. The blockade of PD-1 and its ligand may exacerbate asthma through eosinophilic inflammation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background: Major randomized clinical trials have shown that biological therapy can reduce the exacerbation rate and oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma. However, data on the continuation, efficacy, and safety of biological therapy in older patients with asthma are limited. Therefore, the aim of this study was to evaluate the differences in the continuation rate, efficacy, and safety of biological therapy between older (≥ 65 years) and younger (< 65 years) patients with asthma., Methods: In this single-center retrospective observational study, we collected clinical data of patients with asthma who were administered biological drugs such as omalizumab, mepolizumab, benralizumab, and dupilumab between April 2009 and August 2022. We comparatively analyzed the continuation, efficacy, and safety of biological therapy between older (age ≥ 65 years) and younger patient (age < 65 years) groups. The reasons for discontinuation or switching of biological drugs were also evaluated., Results: Sixty-two (31 older and 31 younger) patients were treated with 91 biologics during the observational period. The mean age of older patients was 74.3 ± 5.1 years and that of younger patients was 48.0 ± 14.0 years. The continuation rate of biological therapy was not significantly different between the groups. Social background was the most common reason for discontinuation of biological therapy in both groups, and insufficient effect was the most common reason for switching to biological drugs. Asthma exacerbations decreased in both groups within the first 12 months of biologic therapy. The dosage of OCS tended to decrease in the older group and significantly decrease in the younger group., Conclusion: Biologic therapy for older patients with asthma can be continued, with efficacy and safety similar to those in younger patients with asthma., Competing Interests: The authors declare no conflict of interest., (©2024 Tottori University Medical Press.)

Background: The occurrence of pulmonary visceral subpleural hematoma during care of post-cardiopulmonary resuscitation including chest compressions and anticoagulant and antiplatelet therapies is extremely rare. Also, there are few reports of treatment of visceral subpleural hematoma, most of which are treated by lung resection. Here we describe a rare case that pulmonary visceral subpleural hematoma arose during post-cardiopulmonary resuscitation care and was treated by hematoma evacuation., Case Presentation: A 58-year-old male with no smoking history and, past medical histories of rheumatoid arthritis, chronic atrial fibrillation, hypertension, diabetes, and dyslipidemia developed ventricular fibrillation due to myocardial infarction and fainted. He received bystander cardiopulmonary resuscitation and defibrillation by the ambulance crew and had return of spontaneous circulation. After transfer to our hospital, the patient underwent percutaneous catheter intervention and stenting with a diagnosis of myocardial infarction, followed by anticoagulant and antiplatelet therapies. On the 8th hospital day, chest radiography suggested right lower lobe pneumonia, and subsequent chest computed tomography revealed pulmonary hematoma in the visceral subpleural area from S6 to S10. Since no improvement was observed in hypoxemia, treatment was considered necessary. First, an attempt at computed tomography-guided drainage of hematoma was made, but insertion of the Pig-tail catheter was difficult due to hardness of the hematoma. Next, evacuation of hematoma was performed on the 13th hospital day. The hematoma was located in the visceral subpleural area and was removed by incising the pleura. TachoSil Tissue Sealing sheet and Polyglycoal acid sheet were applied to the sites of air leakage and oozing after hematoma evacuation. No re-bleeding or air leakage was observed after the treatment, and the patient was discharged on the 26th hospital day after an uneventful course., Conclusions: Pulmonary visceral subpleural hematoma may occur during post-cardiopulmonary resuscitation care, including chest compressions and anticoagulant and antiplatelet therapies. In our case, CT-guided puncture and drainage was difficult and surgical treatment by incision of the visceral pleura and hematoma evacuation alone was done successfully., (© 2024. The Author(s).)

Background and Aim: The differentiation of isolated cortical venous thrombosis (ICVT) from cerebral amyloid angiopathy (CAA) can be difficult because both diseases share similar neurological symptoms and imaging findings. N-methyl- 11 C-2-(4'-methylaminophenyl)-6-hydroxybenzo-thiazole ( 11 C-PiB) positron emission tomography (PET) functions as a diagnostic modality for CAA by detecting amyloid deposition. The present prospective study evaluated amyloid deposition using 11 C-PiB-PET in consecutive patients with suspected ICVT., Method: This study was a prospective observational study. Patients who attended or were hospitalized between May 2019 and March 2020 were included in the analysis. Consecutive patients who met the criteria for suspicion of ICVT were enrolled in the study, and the clinical course, symptoms, imaging findings (including magnetic resonance imaging), and the 11 C-PiB-PET findings of each case were analyzed., Results: The study cohort included four patients (64-82 years of age, all women). In one younger patient, 11 C-PiB-PET afforded no findings suggestive of CAA, whereas the remaining three patients exhibited 11 C-PiB-PET findings suggestive of CAA., Conclusion: Although 11 C-PiB-PET would be a reasonable modality for distinguishing ICVT from CAA, especially in younger patients, it might be difficult to differentiate ICVT from CAA in elderly patients because of the potential deposition of amyloid., Clinical Trial Registration: URL: https://www.umin.ac.jp/ctr/ Unique identifier: UMIN 000037101., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [ 11 C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [ 11 C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Background and Aims: Acute lower gastrointestinal bleeding (ALGIB) increase with age and the administration of antiplatelet drugs. Colonic diverticular bleeding (CDB) is the most common cause of ALGIB, and endoscopic hemostasis is an effective treatment for massive CDB. But in patients without extravasation on contrast-enhanced computed tomography (CECT), the efficacy of urgent colonoscopy (UCS) is controversial from the point of the clinical course, including rebleeding rate. We aimed to establish a potential strategy including UCS for CDB patients without extravasation on CECT., Patients and Methods: Patients from two centers treated for CDB without extravasation on CECT between July 2014 and July 2019 were retrospectively identified (n = 282). Seventy-four underwent UCS, and 208 received conservative management. We conducted two analyses. The first analysis investigates the risk factors of rebleeding rate within 5 days after administration (very early rebleeding), and no UCS (NUCS) was not the independent factor of the very early rebleeding. The second analysis is whether UCS positively influenced the clinical course after hospitalization., Results: The prevalence of very early rebleeding and early rebleeding (6-30 days from admission), patients requiring blood transfusion within 0-5 days and 6-30 days post-admission, and duration of hospitalization were examined as clinical course factors between UCS and NUCS group. There was no significant difference between the UCS and non-UCS groups in the clinical course factors. UCS for the CDB patients without extravasation was not improved rebleeding rate and clinical course., Conclusions: UCS is not necessary in case ofCDB patient without extravasation on CECT., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

A 79-year-old woman collided with a cliff in a passenger automobile. The fire department acknowledged an automated collision notification from the D-Call Net (DCN) at 1 min after the accident and called for doctors by helicopter ( "Doctor-Heli" [DH] in Japan) 9 min after the injury. The DH reached the victim 28 min after the injury, and examination revealed pain in the right side of her chest, tachypnea, and a weak radial artery pulse (indicating shock). The DH arrived at the hospital 49 min after the injury. Thoracic drainage was performed for right-sided tension pneumothorax. She recovered from shock but was diagnosed with flail chest and placed on a respirator. She was extubated on postoperative day 6 and transferred to a rehabilitation hospital on postoperative day 57. Because of the DCN, the patient received treatment 15 min earlier than she would have with the conventional system. Emergency response task forces must develop strategies for connecting DCN warnings to rapid medical response systems.

The formed 4 He (α) clusters consisting of two neutrons and two protons can be a building block in light nuclear systems. Intriguingly, these alpha clusters could potentially form alpha condensate states within the nuclear system. The Hoyle state at 7.65 MeV in 12 C, which plays an essential role in stellar nucleosynthesis, is now considered to be a phase transition, namely the 3α Bose-Einstein condensate. Confirming the existence of Hoyle-analog states in Nα nuclei (N > 3) remains a major challenge. Here we show microscopic five-body calculations for the 20 Ne nucleus. We find that one excited 0 + state has a distinct gas-like characteristic and represents the condensate state. Identifying the 5α condensate state is an important step in establishing the concept of α condensation in nuclear fermion systems., (© 2023. The Author(s).)

Background/aims: The prevalence of inflammatory bowel disease (IBD) in Japan has been increasing. We aimed to clarify the symptoms of patients with IBD in Japan using an internet-based questionnaire survey., Methods: Overall, 805 patients with IBD were asked to complete an internet-based questionnaire addressing their history of disturbances in daily activities, prevalence of fecal urgency, incontinence, and treatment preferences., Results: Responses were obtained from 447 patients with IBD (mean age: 54 years; 70% were men), comprising 363 patients with ulcerative colitis (UC), and 84 with Crohn's disease (CD). Notably, 16% of patients with UC and 35% with CD took over 1 year until the diagnosis of IBD, and 5% of patients with CD visited more than 5 medical institutions. Patients with CD were more likely to experience disturbances in their diet, work, travel, and outings than those with UC. Fecal urgency and incontinence were significantly more frequent in patients with CD than in those with UC (72% vs. 44%, and 50% vs. 26%, respectively). In contrast, 26% of the men and 37% of women with IBD had constipation. Acid reflux, sleep disorders, and depressive symptoms were present in approximately 30% of the patients. Oral administration was preferred., Conclusions: Patients with IBD in Japan experience more severe disturbances in their daily activities, and these are more severe in those with CD than those with UC. In addition to fecal urgency and incontinence, care is required for constipation, acid reflux, sleep disorders, and depressive symptoms., Competing Interests: T.M.: Lecture fee and consultant fee; EA Pharma Co., Ltd. K.I., Y.G., Y.F., T.K., H.K., Y.F., S.I., and M.U.: EA Pharma Co. Ltd., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Objective Vonoprazan (VPZ), clarithromycin (CAM), metronidazole (MNZ) and VPZ, MNZ, and sitafloxacin (STFX) regimen are all established Helicobacter pylori eradication therapies for patients with penicillin allergy in Japan. However, no study has assessed the efficacy of a VPZ, CAM, and MNZ (VCM) regimen in patients with clarithromycin resistance (CAM-R). We therefore assessed the efficacy of a VCM regimen for treating H. pylori infection in patients with CAM-R and penicillin allergy. Methods Fifty-three patients with penicillin allergy who received H. pylori eradication therapy were retrospectively analyzed. Eight patients received a 7-day proton-pump inhibitor, CAM, and MNZ (PCM) regimen; 35 patients [11 CAM-R, and 10 with clarithromycin sensitivity (CAM-S)] received 7-day VCM regimens; and 10 patients received 7-day VPZ, MNZ, and STFX (VMS) regimens. A 13 C-urea breath test was used to determine eradication. The efficacy of eradication was evaluated via both intention-to-treat (ITT) and per-protocol (PP) analyses. Results According to ITT and PP analyses, eradication rates (ERs) with PCM, VCM, and VMS therapies were 50.0% and 50.0%, 94.3% and 100%, and 90% and 90%, respectively. Treatment was successful in all patients with CAM-S. For patients with CAM-R, treatment was successful in 10 patients, and 1 patient discontinued treatment owing to an adverse event. According to ITT and PP analyses, ERs were 90.9% and 100% in CAM-R, and were 100% and 100% in CAM-S, respectively. Conclusion The VCM regimen for H. pylori eradication may be a viable candidate therapy for patients with penicillin allergy, regardless of CAM-R.

Detailed evaluations of body mass index (BMI) and stool form based on the Bristol Stool Form Scale (BSFS) in individuals with constipation, gastroesophageal reflux disease (GERD), and concomitant constipation and GERD have not been performed in Japan. This study was an internet survey conducted to examine the relationships between BMI and constipation, GERD, stool forms based on the BSFS, and education level. This internet-based survey recruited participants from general public survey panels. 10,000 individuals meeting the eligibility criteria were enrolled. Questions included demographics, medical data, and assessments based on validated measures for constipation and GERD. BMI was significantly lower in males with versus without constipation. BMI was significantly higher with GERD both males and females. Mean BMI increased from the BSFS-1/2 group through the BSFS-3/4/5 to the BSFS-6/7 groups in both sexes. BMI was highest in individuals with a maximum education level of junior high school and second highest in individuals completing high school. This is the first real-world survey that closely examines the relationship between BMI and stool forms of individuals in Japan. When the BMI increased, stool forms varied from hard to watery in Japanese people. BMI was related with education level in Japan. (Trial registration: UMIN000039688)., Competing Interests: NO received expenses reimbursement related to this study from EA Pharma Co., Ltd. KK received expenses reimbursement related to this study from EA Pharma Co., Ltd.; research funding from EA Pharma Co., Ltd.; and scholarship donations from AstraZeneca and Daiichi Sankyo Co., Ltd., (Copyright © 2023 JCBN.)

Background: Allergic bronchopulmonary mycosis (ABPM) occurs with fungi, other than Aspergillus fumigatus . However, the clinical characteristics of ABPM caused by non- Aspergillus species are unspecified., Methods: We retrospectively reviewed all patients with ABPM who visited to our hospital between April 2005 and December 2020. The causative fungi and clinical characteristics were analyzed. Patients were divided into the Aspergillus group and the non- Aspergillus group., Results: Fourteen patients and five patients were included in the Aspergillus group and the non- Aspergillus group, respectively. Compared to the Aspergillus group, the non- Aspergillus group had a significantly low serum immunoglobulin E level and low forced vital capacity. In addition, the non- Aspergillus group had a lower rate of the requirement for oral corticosteroid treatment and a low frequency of recurrence., Conclusion: Patients with non- Aspergillus ABPM had lower type 2 inflammation than did patients with allergic bronchopulmonary aspergillosis., Competing Interests: The authors declare no conflict of interests., (©2023 Tottori University Medical Press.)

A 46-year-old man, receiving continuous steroid therapy for refractory ulcerative colitis with an insufficient response to anti-tumor necrosis factor-α therapy, presented with left buttock pain. He was diagnosed with steroidal left femoral head necrosis, and total proctocolectomy with permanent ileostomy was performed. At 6 months postoperatively, the patient developed general fatigue, abdominal pain, and severe ileostomy diarrhea. Computed tomography revealed continuous intestinal edema from the descending duodenal leg to the upper jejunum. Gastrointestinal endoscopy revealed deep ulcers, coarse mucosa, and duodenal erosion. Based on clinical progress, findings, and pathology, the patient was diagnosed with ulcerative colitis-related postoperative enteritis. Although 5-aminosalicylic acid treatment was initiated, his symptoms persisted, bloody diarrhea from colostomy was observed. Subsequently, granulocyte and monocyte apheresis treatment was added. Symptoms and endoscopic findings improved with granulocyte and monocyte apheresis. Azathioprine was introduced as maintenance therapy, and no sign of recurrence was observed. Although ulcerative colitis-related postoperative enteritis has no definitive treatment, granulocyte and monocyte apheresis may be considered for initial treatment., (© 2022. Japanese Society of Gastroenterology.)

Case Presentation: A 40-year-old woman was injured in a motor vehicle accident. Physician-staffed helicopter emergency medical service (HEMS) was dispatched, and after the HEMS physician performed thoracostomy and tracheal intubation to relieve the tension pneumothorax and hemorrhagic shock, her carotid artery became unpalpable. The physician then decided to perform prehospital resuscitative thoracotomy. Immediately after arriving at the hospital, an emergency laparotomy was performed. Intraoperative findings showed that a huge uterine fibroid had been avulsed from the uterine wall, and we performed temporary hemostasis by extraction of the avulsed tumor and application of packing to the pelvic cavity. She was transferred to a rehabilitation hospital 42 days after the operation., Conclusion: The injury mechanism in this case was considered a "submarine effect." This was an extremely rare case in which the acute care surgeon and a gynecologist collaboratively employed a damage control strategy to deal with impending cardiac arrest., (© 2022 The Authors.)

Background: Jackhammer esophagus (JE) is a hypercontractile esophageal motility disorder diagnosed using high-resolution manometry (HRM). We sought to determine the clinical presentation and therapeutic data of patients with JE in Japan., Methods: The study included patients with JE, diagnosed through HRM performed for suspicious esophageal motility disorders. Demographics, esophagogastroduodenoscopy, radiology, and therapy data were collected from patient charts., Results: Among the 4,412 HRM tests performed, 89 patients (61.6 ± 13.4 years; 64 males, 25 females) were diagnosed with JE (2.0%). Dysphagia was the most frequent symptom (80%), followed by chest pain (40%) and heartburn (25%). Esophagogastroduodenoscopy showed abnormal findings in 32% of patients: corkscrew/rosary beads appearance in 26%, narrowing in 11%. Eosinophilic infiltration (> 15 eosinophils/high power field) was diagnosed in 21%. Esophagography showed abnormal findings in 9% of the patients. For the initial therapy, 47 patients received medical treatment followed by peroral endoscopic myotomy (21 patients) and laparoscopic myotomy (two patients). Thirteen patients did not receive any treatment and 10 of those (77%) reported spontaneous resolution of symptoms. Patients who required invasive treatment experienced severe disability in their quality of life and greater maximal distal contractile integral than those who did not., Conclusions: HRM showed that the prevalence of JE was very low (2%). Esophagogastroduodenoscopy revealed some characteristic features of JE in patients. Some patients showed improvement of symptoms without invasive treatments. Follow-up with/without medical treatment should be considered before performing invasive treatment in patients whose distal contractile integral is relatively low and the quality of life is not impaired., (© 2022. The Author(s).)

Herein, we describe a case of olmesartan-related sprue-like enteropathy in which improvement in villous atrophy was confirmed by small-bowel capsule endoscopy (CE). We successfully treated a 66-year-old man with a chief complaint of loose diarrhea. The patient had persistent watery diarrhea 10 times a day and experienced a weight loss of 9 kg in 3 months. An abdominal computed tomography scan showed fluid retention in the small intestine. Blood test results revealed no inflammatory reaction. Esophagogastroduodenoscopy detected villous atrophy in the stomach and duodenum. Moreover, small-bowel CE showed villous atrophy in about two-thirds of the small intestine. Based on other examinations, hyperthyroidism, intestinal tuberculosis, intestinal amyloidosis, and intestinal malignant lymphoma were ruled out. Therefore, the patient was suspected of having an olmesartan-related sprue-like disease. Early after discontinuation of medication, diarrhea symptoms improved, and a repeat CE indicated improvements in small intestinal villous atrophy. Since the patient had been administered olmesartan for a long time and CE showed villous atrophy throughout the small bowel, we suspected him of having the olmesartan-associated sprue-like disease. The findings of gastric mucosa atrophy on esophagogastroduodenoscopy may lead to an early diagnosis of this disease. Olmesartan-related sprue-like enteropathy should be considered as a differential diagnosis in patients with chronic severe watery diarrhea., Competing Interests: None., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Aseptic meningitis is a rare immune-related adverse event (irAE), which occurs during treatment with immune checkpoint inhibitors (ICIs). This condition has non-specific symptoms and exhibits no clear signs on magnetic resonance imaging (MRI). There are only a few reports of aseptic meningitis caused by pembrolizumab treatment for non-small cell lung cancer (NSCLC). The present study includes a report of such a case and a review of the related literature. A 67-year-old Japanese man received first-line pembrolizumab treatment for NSCLC and subsequently developed severe nausea and vomiting. No significant findings were observed following a computed tomography (CT) scan, MRI of the brain and upper gastrointestinal tract, or upper gastrointestinal endoscopy. Cerebrospinal fluid analysis revealed lymphocyte infiltration and elevation of the IgG index, without indications of metastasis or infection, which suggested the presence of aseptic meningitis. The symptoms immediately improved following prednisolone treatment, and aseptic meningitis was diagnosed as an irAE related to pembrolizumab treatment. Given that aseptic meningitis can cause non-specific symptoms, including headache and nausea, the possibility of an irAE should be considered in patients with non-specific symptoms who are receiving ICIs, and a cerebrospinal fluid examination should be performed., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Inui et al.)

Background/aims: Detailed evaluations of overlapping constipation and gastroesophageal reflux disease (GERD) have not been conducted in Japan. The REACTION-J2 study examined the overlap of these diseases in Japan., Methods: This internet-based survey recruited participants from general public survey panels. Questions included demographic and medical data and assessments based on validated measures for constipation and GERD. Associations between background factors affecting constipation/GERD overlap, disease measures, and treatment were also evaluated., Results: Among 10 000 survey responses received, functional constipation (Rome IV diagnostic criteria) was reported by 439 participants; chronic constipation (Japanese guidelines) by 3804 participants; and subjective constipation symptoms by 2563 participants. The number of participants with constipation/GERD overlap ranged from 73 to 1533 depending on the criteria used. Regardless of the definition used, all GERD groups had significantly higher odds of being constipated than non-GERD participants: the OR (95% CI) for all 9 combinations of definitions ranged between 1.56 (1.21, 2.01) and 2.67 (2.44, 2.92) (all P ≤ 0.001). Straining, hard stools, and sensations of incomplete evacuation and anorectal obstruction/blockage, according to chronic constipation criteria, were common. Participants with constipation/GERD overlap had poorer quality of life ( P < 0.001) and worse GERD symptom scores ( P < 0.001). The frequency of abnormal stools was highest ( P < 0.001) in the constipation/GERD overlap group. In the overlap group, 52.4% and 26.0% used gastric and constipation medication, respectively., Conclusion: Individuals with constipation/GERD overlap tend to have worsened symptoms and quality of life.

Background: Tumor necrosis factor (TNF)-α, a proinflammatory cytokine, is involved in the pathogenesis of rheumatoid arthritis (RA). The omega-3 unsaturated fatty acid-derived metabolites resolvin (Rv) D1, RvE1, and maresin-1 (MaR1) have been reported as anti-inflammatory lipid mediators and are known as specialized pro-resolving mediators (SPMs). In this study, we aimed to investigate the anti-inflammatory effects of SPMs on TNF-α-induced responses in synovial fibroblasts., Methods: We investigated the effects of SPMs on gene expression and/or production of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), interleukin (IL)-6, and matrix metalloproteinase (MMP)-3, which are involved in TNF-α-induced synovitis in RA or OA synovial fibroblasts, by quantitative real-time PCR. We also investigated the effects of SPMs on the mitogen-activated protein kinase (MAPK) signaling pathway by western blotting. Anti-inflammatory effects of SPMs were evaluated by applying SPMs to cultured synovial fibroblasts, followed by TNF-α stimulation., Results: The induction of COX-2, mPGES-1, IL-6, and MMP-3 by TNF-α in synovial fibroblasts was not suppressed by omega 3-derived SPMs regardless of their origin such as RA or OA. SPMs had no effect on lipid mediator receptor gene expression induce by TNF-α and did not inhibit the TNF-α-activated MAPK signaling pathway. The production of COX-2 and IL-6 protein was significantly decreased by p38 inhibitor., Conclusion: Despite reports on the anti-inflammatory effect of omega 3-derived SPMs, its anti-inflammatory effect on TNF-α-induced responses was not observed in synovial fibroblasts. The reason may be that SPMs have no suppressive effect on p38 activation, which plays an important role in the production of inflammatory cytokines in synovial fibroblasts., Competing Interests: The authors declare no conflict of interest., (©2022 Tottori University Medical Press.)

A 62-year-old man was referred to our hospital because of abdominal pain. Computed tomography revealed an approximately 7-cm-diameter tumor in the left abdomen with metastatic lymph nodes, an approximately 1-cm-diameter round tumor in contact with the subclavian artery in the apical lobe of the right lung, and mediastinal lymph node enlargement in contact with the superior vena cava. Esophagogastroduodenoscopy and colonoscopy revealed no abnormalities. Double-balloon endoscopy revealed a whole circumferential ulcer in the jejunum approximately 20 cm from the ligament of Treitz. Biopsy analysis of an ulcer specimen revealed a poorly differentiated carcinoma. Immunohistochemical staining of the specimen showed that it was positive for thyroid transcription factor 1 and cytokeratin 7 and negative for cytokeratin 20, GATA-binding protein 3, caudal-type homeobox protein 2, and paired box 8. Positron emission tomography revealed positive findings in the small-intestinal tumor, nearby mesenteric lymph nodes, lymph nodes around the abdominal aorta, lung tumor, and mediastinal lymph node in the apical lobe of the right lung. Accordingly, the patient was diagnosed as having a lung carcinoma with small-intestinal metastasis (T1b, N3, M1c; cStage IVB). Pathological examination helped distinguish the primary small-intestinal tumor from the metastatic small-intestinal tumor and detect the tumor origin., Competing Interests: The authors declare no conflicts of interest pertaining to this manuscript., (Copyright © 2022 by S. Karger AG, Basel.)

Gastric plexiform fibromyxoma is extremely rare. In our case, upper gastrointestinal endoscopy of a 41-year-old woman patient revealed a 1-cm submucosal tumor (SMT) in the greater curvature of the lower body of the stomach. On contrast-enhanced computed tomography, the tumor was hypervascular in the arterial phase with continuous enhancement in the post-venous phase. On endoscopic ultrasonography, it had a low echo pattern. The preoperative diagnosis was a gastric SMT with a rich vasculature; however because the biosy specimen did not contain tumor tissue, a malignant tumor could not be excluded. The patient underwent nonexposed endoscopic wall-inversion surgery (NEWS), and the tumor was completely resected. Immunohistochemical examination revealed that the tumor was positive for D2-40 and α-smooth muscle actin, but negative for c-kit, discovered on gastrointestinal stromal tumor-1, desmin, S100, Melan-A, signal transducer and activator of transcription 6, insulinoma-associated protein 1, CXCL13, ETS transcription factor, follicular dendritic cell, anaplastic lymphoma kinase, human melanoma black, h-caldesmon, and CD1a, 10, 21, 23, 31, 34, 68, and 163. Approximately, 1-2% of the tumor cell nuclei were Ki-67-positive. Finally, we diagnosed the tumor as a plexiform fibromyxoma. In conclusion, NEWS is an effective method for the treatment of SMTs with a diameter of <3 cm., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 by S. Karger AG, Basel.)

Background: Functional constipation (FC), a functional bowel disorder with symptoms of constipation, has considerable impact on quality of life. As data regarding its prevalence and epidemiology are lacking, this study aimed to evaluate the prevalence, population composition, lifestyle, quality of life, and clinical characteristics of these individuals by comparing people with and without FC. These parameters were also compared among individuals with strong and weak awareness of constipation., Methods: An internet survey was conducted among 10,000 individuals aged 20-69 years from the general Japanese population; they were registered with an internet survey company. The following data were obtained: age, sex, educational history, occupation, residence, history of other diseases, lifestyle (including smoking/drinking habits using the Japanese Health Practice Index, medication use, symptoms of constipation according to the Rome III criteria, stool types according to the Bristol stool scale, and use of laxatives, including the place of purchase and cost per month or acceptable cost per month. The 8-item Short Form Health Survey Questionnaire was also used; FC was diagnosed based on Rome III criteria. All respondents were classified according to their awareness of constipation (i.e. strong or weak), and their characteristic features were compared., Results: The data of 3000 respondents were evaluated; 262 (8.7%) had FC, which was common among older adults, women, and homemakers. FC was associated with changes in the frequency of bowel movement, sensation of incomplete or scanty evacuation, and the use of manual maneuvers; these are consequential clinical symptoms of FC. These individuals frequently skipped breakfast, had insufficient sleep, had more severe constipation, and had purchased laxatives in pharmacies or online more often than those without FC. A strong awareness of constipation was significantly more prevalent among women and homemakers. A history of anemia and cardiovascular disease was significantly more frequent in the strong awareness group, whereas a history of hypertension was more frequent in the weak awareness group., Conclusions: Appropriate and comprehensive management should be provided for FC, based on the understanding of its characteristic features and considering the symptoms and lifestyle., (© 2022. The Author(s).)

Purpose: Small animal PET provides the biodistribution of administrated radiotracer in vivo and have a potential to contribute on dosimetry study. The aim of this study is to investigate the effect of region-of-interest (ROI)-delineation in whole-body rat PET image toward non-invasive estimation of human dosimetry of 18 F-FDG., Method: After administration of 18 F-FDG (averaged 11.7 MBq), 3.5-h PET and 20-min CT scans were sequentially performed for three rats by Clairvivo PET/CT system. Seven source organs, and the remainder of the body, were studied to extrapolate %ID(t) and estimate time-integrated activity coefficients [kBq-h/MBq] in human. The mean absorbed dose in each target organ and the effective dose were estimated by MIRD method. Effects of ROI-definitions on both extrapolated %ID(t) in human and estimated doses were also investigated by using (i) small ROIs of high uptake region and (ii) whole organ ROIs., Results: Averaged effective doses of 18 F-FDG in human by using high-uptake and whole-organ ROIs were 27.8 ± 6.54 and 19.3 ± 2.72 μSv/MBq, respectively., Conclusion: The use of small animal PET scanner, which allows repeatedly PET scans, have a potential to contribute on the reduction of the number of experimental animals. However, the ways of ROI drawing influences on the estimated effective dose and safe-side ROI definition may be preferred., (Copyright © 2021 Elsevier Ltd. All rights reserved.)