A novel method to localize patency capsule by ileo-colonoscopy facilitates endoscopic assessment of the small and large intestine in patients with Crohn's disease.

INTRODUCTION: Patients with Crohn's disease (CD) require an assessment of small bowel lesions, while difficulties exist in performing small intestinal examinations especially in small-sized medical offices. Small bowel capsule endoscopy (SBCE) is handy and can be performed in most clinical settings. The only drawback of SBCE is a requirement of patency testing prior to the exam because it sometimes requires CT scanning to localize the ingested patency capsule (PC), which may be a substantial burden for the patient. We have developed a novel PC detection system named PICS (Patency capsule, Ileo-Colonoscopy and Small bowel capsule endoscopy) method by which we can avoid CT scanning. In the PICS method, Ileo-Colonoscopy (ICS) is performed after 30 to 33 hours of PC ingestion and the PC can be localized by ICS in patients who have not excreted the PC, and the entire intestine can be examined in combination with subsequent SBCE without additional bowel preparation. The aim of this study was to assess the usefulness and safety of the PICS method for CD patients. METHODS: CD patients who underwent PICS method from April 2021 to March 2023 were reviewed for clinical data, outcome of PICS method including the rates of PC detection by ICS, the number of patients underwent SBCE, and adverse events. Lewis score was used to assess SBCE results. RESULTS: The PICS method was performed in 54 patients. The median age of patients was 28.5 years old and 64.8% of them were ileo-colic type. The median disease duration was 10.5 months and 24.1% had history of small bowel resection. Five cases (9.3%) confirmed gastrointestinal patency by ICS and none of the cases required CT scanning. One patient who could not be confirmed patency by ICS, and the other patient who excreted PC but was found ileal stenosis by ICS did not undergo SBCE. Remaining 52 patients received SBCE and the median Lewis score of them was 0 (IQR 0, 450). There were no adverse events including small bowel obstruction by PC and SBCE retention in this series. CONCLUSION: The PICS method is not only feasible and safe but also convenient to assess disease extent in patients with CD. By localizing PC with ICS, additional CT scanning could be unnecessary for SBCE, which benefits both physicians and CD patients.

Supersulphides provide airway protection in viral and chronic lung diseases.

Supersulphides are inorganic and organic sulphides with sulphur catenation with diverse physiological functions. Their synthesis is mainly mediated by mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulphide synthase (CPERS). Here, we identify protective functions of supersulphides in viral airway infections (influenza and COVID-19), in aged lungs and in chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF). We develop a method for breath supersulphur-omics and demonstrate that levels of exhaled supersulphides increase in people with COVID-19 infection and in a hamster model of SARS-CoV-2 infection. Lung damage and subsequent lethality that result from oxidative stress and inflammation in mouse models of COPD, IPF, and ageing were mitigated by endogenous supersulphides production by CARS2/CPERS or exogenous administration of the supersulphide donor glutathione trisulphide. We revealed a protective role of supersulphides in airways with various viral or chronic insults and demonstrated the potential of targeting supersulphides in lung disease.

Impact of accumulative smoking exposure and chronic obstructive pulmonary disease on COVID-19 outcomes: report based on findings from the Japan COVID-19 task force.

OBJECTIVES: Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for severe COVID-19. However, limited literature exists on the effect of COPD and smoking on COVID-19 outcomes. This study examined the impact of smoking exposure in pack-years (PY) and COPD on COVID-19 outcomes among smokers in Japan. METHODS: The study included 1266 smokers enrolled by the Japan COVID-19 task force between February 2020 and December 2021. PY and COPD status was self-reported by patients. Patients were classified into the non-COPD (n = 1151) and COPD (n = 115) groups; the non-COPD group was further classified into <10 PY (n = 293), 10-30 PY (n = 497), and >30 PY (n = 361). The study outcome was the need for invasive mechanical ventilation (IMV). RESULTS: The incidence of IMV increased with increasing PY and was highest in the COPD group (<10 PY = 7.8%, 10-30 PY = 12.3%, >30 PY = 15.2%, COPD = 26.1%; P <0.001). A significant association was found for IMV requirement in the >30 PY and COPD groups through univariate (odds ratio [OR]: >30 PY = 2.11, COPD = 4.14) and multivariate (OR: >30 PY = 2.38; COPD = 7.94) analyses. Increasing PY number was also associated with increased IMV requirement in patients aged <65 years. CONCLUSION: Cumulative smoking exposure was positively associated with COVID-19 outcomes in smokers.

A Novel Development of Sarcoidosis Following COVID-19 Vaccination and a Literature Review.

BNT162b2 (Pfizer/BioNTech) is a coronavirus disease 2019 (COVID-19) vaccine containing nucleoside-modified messenger RNA encoding the severe acute respiratory syndrome coronavirus 2 spike glycoprotein. Recently, ocular complications of mRNA vaccines have been reported increasingly frequently. However, immunological adverse events due to mRNA vaccines in real-world settings are not fully known. We herein report the novel development of sarcoidosis manifested as uveitis, bilateral hilar lymphadenopathy, angiotensin-converting enzyme elevation, and epithelioid and giant cell granuloma formation in the lung soon after the first BNT162b2 injection and review the current literature, including three reported cases of sarcoid-like reaction following COVID-19 vaccination.

COVID-19 in a Hairy Cell Leukemia Patient: A Rare Case Report.

The detailed clinical course of coronavirus disease 2019 (COVID-19) in patients with hairy cell leukemia (HCL) is rarely reported. We report the first case of HCL diagnosed with prolonged pancytopenia after COVID-19 infection in Japan. We describe the case of a 56-year-old man who was diagnosed with COVID-19. Computed tomography revealed ground-glass opacities in the bilateral lung lobes as well as splenomegaly. Remdesivir and dexamethasone were administered for the treatment of COVID-19. Since the pancytopenia persisted, bone marrow examination was performed, and he was diagnosed with HCL. Although pancytopenia can occur with COVID-19 alone, clinicians should be alerted regarding the presence of hematologic malignancies in patients in whom pancytopenia persists after COVID-19 treatment or in those with splenomegaly. Further, the condition of all previously reported patients with COVID-19 associated with HCL was severe enough to require mechanical ventilation. This is the first case in which the disease was not severe. The interleukin-6 (IL-6) level was lower in this case than in previous cases, suggesting that racial differences in IL-6 production may have contributed to COVID-19 severity.

[A case of advanced pancreatic cancer with spontaneous tumor lysis syndrome].

A 74-year-old male with pancreatic cancer and multiple huge liver metastases received palliative care due to the cancer progression after chemotherapy. The patient was admitted to our hospital for increased abdominal pain and dehydration. Tumor lysis syndrome was diagnosed on the fifth hospital day owing to the advancement of renal impairment, hyperuricemia, hyperkalemia, and hyperphosphatemia. The patient's condition rapidly deteriorated despite increased intravenous infusion and the provision of antihyperuricemia medicine and demised on the seventh hospital day. Autopsy results revealed generalized necrosis of the tumor, consistent with tumor lysis syndrome.

PGC-1α regulates airway epithelial barrier dysfunction induced by house dust mite.

BACKGROUND: The airway epithelial barrier function is disrupted in the airways of asthmatic patients. Abnormal mitochondrial biogenesis is reportedly involved in the pathogenesis of asthma. However, the role of mitochondrial biogenesis in the airway barrier dysfunction has not been elucidated yet. This study aimed to clarify whether the peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), a central regulator of mitochondrial biogenesis, is involved in the disruption of the airway barrier function induced by aeroallergens. METHODS: BEAS-2B cells were exposed to house dust mite (HDM) and the expressions of PGC-1α and E-cadherin, a junctional protein, were examined by immunoblotting. The effect of SRT1720, a PGC-1α activator, was investigated by immunoblotting, immunocytochemistry, and measuring the transepithelial electrical resistance (TEER) on the HDM-induced reduction in mitochondrial biogenesis markers and junctional proteins in airway bronchial epithelial cells. Furthermore,the effects of protease activated receptor 2 (PAR2) inhibitor, GB83, Toll-like receptor 4 (TLR4) inhibitor, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), protease inhibitors including E64 and 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) on the HDM-induced barrier dysfunction were investigated. RESULTS: The amounts of PGC-1α and E-cadherin in the HDM-treated cells were significantly decreased compared to the vehicle-treated cells. SRT1720 restored the expressions of PGC-1α and E-cadherin reduced by HDM in BEAS-2B cells. Treatment with SRT1720 also significantly ameliorated the HDM-induced reduction in TEER. In addition, GB83, LPS-RS, E64 and AEBSF prevented the HDM-induced reduction in the expression of PGC1α and E-cadherin. CONCLUSIONS: The current study demonstrated that HDM disrupted the airway barrier function through the PAR2/TLR4/PGC-1α-dependent pathway. The modulation of this pathway could be a new approach for the treatment of asthma.

Nitrosative stress in patients with asthma-chronic obstructive pulmonary disease overlap.

BACKGROUND: Asthma-chronic obstructive pulmonary disease overlap (ACO) has frequent exacerbations and a poor quality of life and prognosis compared with those of chronic obstructive pulmonary disease alone. However, the pathogenesis of ACO has not been fully elucidated yet. OBJECTIVES: The aim of this study was to investigate nitrosative stress, which causes a redox imbalance and tissue inflammation in the airways of patients with ACO, and to evaluate the relationship between nitrosative stress and the clinical course in study subjects. METHODS: Thirty healthy subjects and 56 asthmatic patients participated in this study. The asthmatic patients were divided into 33 asthmatic patients and 23 patients with ACO. The study subjects had been followed prospectively for 2 years to evaluate the clinical course. Nitrosative stress was evaluated based on the production of 3-nitrotyrosine (3-NT) in sputum cells. RESULTS: Production of 3-NT was significantly enhanced in patients with ACO compared with that in asthmatic patients. Amounts of reactive persulfides and polysulfides, newly identified powerful antioxidants, were significantly decreased in the ACO group. Baseline levels of 3-NT were significantly correlated with the frequency of exacerbations and decrease in FEV1 adjusted by age, smoking history, and blood eosinophil count. The 3-NT-positive cells were also significantly correlated with amounts of proinflammatory chemokines and cytokines. CONCLUSIONS: These findings suggested that greater nitrosative stress occurred in the airways of patients with ACO, and the degree of nitrosative stress was correlated with an impairment in the clinical course. Nitrosative stress might be related to the pathogenesis of ACO.

A novel case of functional gastric neuroendocrine carcinoma occurred after endoscopic submucosal dissection.

In Japan, endoscopic submucosal dissection (ESD) is becoming a standard treatment for intramucosal differentiated gastric cancer. Although ESD is associated with a high cure rate for patients with early gastric cancer, tumors may recur, albeit rarely. We performed ESD on an 80-year-old man with a small depressed type of gastric cancer of the posterior wall of the cardia, found to be locally invasive on histology. Thirty months later, local recurrence and multiple liver metastases were detected, accompanied by frequent severe hypoglycemia. Despite chemotherapy, the patient died 6 months after relapse. On autopsy, the recurrent gastric lesion and liver metastases were examined immunohistochemically. Several characteristic tumor cells were positive for chromogranin A, cluster of differentiation (CD) 56, Ki-67, and insulin-like growth factor (IGF)-II. Western blot analysis of the patient's serum obtained during a hypoglycemic attack showed the high molecular weight form of IGF-II or "big" IGF-II. The patient was diagnosed with non-islet cell tumor hypoglycemia (NICTH), with "big" IGF-II being produced by the gastric neuroendocrine carcinoma. This is the novel case of a functional gastric neuroendocrine carcinoma that occurred after ESD and induced a hypoglycemic attack associated with NICTH.

Eosinophilic esophagitis: a case report with a review of the literature.

Eosinophilic esophagitis (EE) is an allergic inflammatory condition of the esophagus and is characterized by dense eosinophilic infiltration of the esophagus. There has been a dramatic increase in the diagnosis of EE in Western countries in recent years; however, in Japan, there are very few reports of EE. We present a rare case of EE in a 70-year-old Japanese woman, who had dysphasia for 2 years, but which worsened over a 6-month period. Laboratory examinations showed peripheral eosinophilia (1279/µl). Significant thickening of the esophageal wall was observed on computed tomography scan and many circular rings appeared when an esophagogastroduodenoscopy was carried out. From these circular rings, EE was suspected and a biopsy was then taken from the esophagus. As the histologic findings from the esophageal biopsy showed that >25 eosinophils existed per high-power field, the patient was diagnosed with EE. Oral corticosteroid (prednisolone 30 mg/day) therapy was administered and after 3 days of treatment her symptoms almost disappeared. EE needs to be considered as a differential diagnosis if patients with non-erosive reflux disease have dysphagia but do not respond to high-dose proton pump inhibitor therapy.

The appearance of rosette-like esophageal folds ("esophageal rosette") in the lower esophagus after a deep inspiration is a characteristic endoscopic finding of primary achalasia.

BACKGROUND: In healthy subjects who inspire deeply the lower esophagus usually opens, and the esophageal palisade vessels (EPVs) become visible. However, in patients with achalasia, the full extent of the EPVs does not become visible and, in addition, rosette-like esophageal folds appear in the lower esophagus. The aim of this study was to investigate whether or not these changes at the lower esophagus are characteristic findings of achalasia. METHODS: A total of 34 patients with achalasia and no esophageal dilatation following deep inspiration were compared with 34 sex- and age-matched control subjects. Following a deep inspiration, the lower esophagus of all study cohorts was evaluated on (1) whether or not the full extent of the EPVs was visible, (2) whether or not rosette-like esophageal folds appeared in the lower esophagus, and (3) whether or not there were any gastric lesions. RESULTS: One patient had secondary achalasia, and the remaining 33 patients had primary achalasia. In the control subjects, the full extent of the EPVs was clearly visible after a deep inspiration, and no esophageal folds appeared in the lower esophagus. In contrast, in the achalasia patients, EPVs were not observed in all patients after a deep inspiration, and rosette-like esophageal folds appeared in 33 of the 34 patients. CONCLUSION: After a deep inspiration, the non-visibility of the EPVs and the appearance of rosette-like esophageal folds at the lower esophagus, which we have called "esophageal rosette", are characteristic endoscopic findings of primary achalasia.

[Management of gastroesophageal reflux disease (GERD) with refractory to standard dose of proton pump inhibitor].

Approximately 10% of Japanese patients with reflux esophagitis (RE) are refractory to a standard dose of proton pump inhibitor(PPI) and most refractory patients have severe RE. Lack of response may be due to inadequate gastric acid suppression in conjunction with CYP2C19 genotype status and nocturnal acid reflux. Twice-daily dosing of PPI for inadequate gastric acid suppression and the administration of H2-receptor antagonist before bedtime for nocturnal acid reflux, is effective in most cases. The response to a standard dose of PPI in patients with non-erosive reflux disease (NERD) is approximately 50%. The reasons for a lower response rate, compared with RE patients, are not clear but may relate to an acid-hypersensitive esophagus, inadequate gastric acid suppression, non -acid reflux and emotional or psychological abnormality. High dose PPI therapy, endoscopic or surgical anti-reflux therapy, or/and pain modulators may be effective in some patients.