Objective Gastrointestinal lesions of non-tuberculous mycobacteria (NTM) are regarded as opportunistic infections. A large number of positive specimens of NTM were identified in an intestinal fluid culture in the endoscopy unit and it was considered to be a pseudo-outbreak.

Methods We reviewed the hospital, laboratory, and colonoscopy records of 263 consecutive patients whose intestinal fluids were analyzed for a mycobacterial culture by colonoscopy at St. Marianna University Hospital, between January 2009 and December 2018. The endoscopy reprocessing procedures were reviewed and samples of water used in the endoscopy unit were cultured.

Results An intestinal fluid culture of 154 (58.6%) patients tested positive for NTM (M. intracellulare; 125 cases, M. gordonae; 14 cases, M. avium; 4 cases, M. abscessus; 3 cases, and 8 other cases). In 182 cases (69.2%), an intestinal mucosal culture was performed simultaneously with a fluid culture and tested positive for NTM in 2 cases. Next, we examined the endoscopy unit for any possible environmental contamination. NTM were detected in the tap water used to prepare the antifoaming solution in the endoscopy unit. The water faucets in the endoscopy unit were considered to be the source of the contamination of NTMs.

Conclusion We observed that a large number of cases tested positive due to contaminated water that had been used in an endoscopy unit, thus leading to a pseudo-outbreak of NTM.

Objective This retrospective study was performed to investigate the anti-Helicobacter pylori IgG antibody serum titers in H. pylori-negative subjects with different degrees of gastric mucosal atrophy including C0 grade atrophy.

Methods The absence of H. pylori infection was determined based on both negative serum anti-H. pylori IgG antibody test findings and no endoscopic evidence of that infection. Cases negative for the antibody and with positive endoscopic findings of H. pylori infection were defined as H. pylori-positive. The serum anti-H. pylori IgG antibody titers were analyzed in H. pylori-negative (n=1,087), -positive (n=69), and post-eradicated (n=278) subjects.

Results The serum antibody titer in subjects with H. pylori-positive endoscopy findings was significantly higher than that in H. pylori-negative subjects, even when the serum titer indicated a negative result. In addition, the anti-H. pylori IgG antibody serum titer was higher in H. pylori-negative subjects with a greater degree of gastric mucosal atrophy. In a comparison between H. pylori-negative C0 and C1 gastric mucosal atrophy cases, the antibody serum titer in those classified as C0 was significantly lower. An analysis of H. pylori post-eradicated cases showed that the serum antibody titer decreased over time after successful eradication.

Conclusion The disappearance of H. pylori infection in H. pylori-negative individuals may occur later in those with a greater degree of gastric mucosal atrophy. The serum antibody titer difference between the H. pylori-negative C0 and C1 groups might have been caused by the differences in distribution between H. pylori-uninfected subjects and those in whom the infection had disappeared, thus additional investigation is needed to clarify the significance of gastric mucosal classification including the C0 grade.

Objective There is a paucity of information on whether the hepatitis B virus (HBV) vaccine, derived from HBV genotype C, can prevent mother-to-child transmission of HBV genotype D. The aim of this study was to clarify this issue.

Methods The subjects consisted of 25 children (8.5±4.1 years old, 7 males, 18 females), born to 17 mothers who were chronically infected with HBV genotype D. Of these, 20 children were inoculated with the genotype C-derived vaccine, one was inoculated with the genotype A-derived vaccine, and one was inoculated with both the A- and C-derived vaccines. Information on the type of vaccine given to the remaining three children was not available. The serum levels of HB surface antigen (HBsAg), antibody to HBsAg (anti-HBs), and antibody to HB core (anti-HBc) of the children, as well as HBV markers of the mothers, were examined.

Results All mothers were positive for HBsAg (6,563±11,005 IU/mL), negative for HBeAg, and positive for anti-HBe. HBV-DNA levels (log IU/mL) were <3.3 in 7 mothers, 3.3-4.3 in 9 mothers, and >4.3 in one mother. HBsAg and anti-HBc were negative in all children, regardless of the type of vaccine used. Anti-HBs were positive in 13 children and negative in 12.

Conclusion All children born to mothers infected with genotype D, including 20 who were inoculated with the genotype C-derived vaccine, were negative for both HBsAg and anti-HBc. These results suggest that the genotype C-derived HB vaccine is effective in preventing mother-to-child transmission from mothers infected with HBV genotype D.

Objective We recently reported that routine cardiac computed tomography (CT) scans for radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) could steadily detect coronary artery lesions (CALs) and could accurately detect myocardial ischemia in 9% of patients with AF who underwent RFCA of AF. The aim of this study was to identify the independent risk factor (s) of myocardial ischemia in those patients.

Methods Patient characteristics, blood test, CALs, Ordinal coronary calcium scoring (OCCS), and myocardial Ischemia (MI) were evaluated in 757 consecutive patients who underwent RFCA of AF.

Results There were 685 and 72 patients without and with myocardial ischemia, respectively. A univariate analysis and multivariate statistical analysis revealed that a male gender (Odds ratio 2.11), a high number of co-existing coronary risk factors (NCCRF ≥3) (Odds ratio 2.03), an elevated brain natriuretic peptide level (BNP ≥100 pg/mL) (Odds ratio 3.37), an enlarged left atrial volume (≥90 mL) (Odds ratio 2.91), and a high OCCS (≥4) (Odds ratio 13.0) were independent risk factors of myocardial ischemia in patients undergoing RFCA of AF.

Conclusion The high OCCS (≥4) by cardiac CT was the strongest independent risk factor of myocardial ischemia in those patients. However, physicians may be able to find the high risk patients of myocardial ischemia by evaluating a male gender, in the presence of a high NCCRF (≥3) and elevated BNP (≥100 pg/mL) without OCCS by cardiac CT in patients undergoing RFCA of AF.

Objective Home care is important in patients with heart failure (HF) in order to maintain their quality of life. A biomarker that can be measured noninvasively is needed to optimize the home care of patients with HF. Urinary angiotensinogen (uAGT) is an indicator of the intrarenal renin-angiotensin system activity, which may be augmented in HF. We hypothesized that uAGT might be a urinary biomarker in HF.

Methods We measured uAGT by an enzyme-linked immunosorbent assay and uAGT normalized by urinary creatinine (uCr)-designated uAGT/uCr-at admission and discharge in 45 patients hospitalized for HF.

Results We found that both uAGT/uCr [median (interquartile range): 65.5 (17.1-127.7) μg/g Cr at admission; 12.1 (6.0-37.0) μg/g Cr at discharge; p<0.01] and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels [5,422 (2,280-9,907) pg/mL at admission; 903 (510-1,729) pg/mL at discharge; p<0.01] significantly decreased between admission and discharge along with an improvement in patient's clinical status [New York Heart Association scores: 3 (3-4) at admission; 1 (1-1) at discharge; p<0.01]. The generalized least squares model revealed that the time course changes in uAGT/uCr also correlated with those in NT-proBNP levels between admission and readmission in five patients readmitted for HF.

Conclusion The results indicated that the time course changes in uAGT/uCr correlated with those in the NT-proBNP levels in patients with HF who showed a clinical improvement. Further investigation and development of a kit for the rapid measurement of uAGT are needed to evaluate the clinical utility of uAGT as a biomarker in HF.

Objective Mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, is effective for treating eosinophilic severe asthma. However, there is a need for more biomarkers that can predict the patient response to mepolizumab before starting therapy. This study aimed to identify a new biomarker in the serum that is able to accurately predict the responsiveness to mepolizumab.

Methods This study enrolled 11 patients who had all been diagnosed with severe eosinophilic asthma and were then administered mepolizumab every 4 weeks for at least 4 months. Blood samples were collected, and pulmonary function tests and questionnaires were administered at baseline and after 4, 8 and 16 weeks of treatment. The response to mepolizumab was then assessed based on the difference in the Asthma Quality of Life Questionnaire (AQLQ) score after 16 weeks of mepolizumab therapy compared with that at baseline. Patients with an increase in the AQLQ score of more than 0.5 were defined as responders. The cytokine levels in the blood were measured by LUMINEX 200 and ELISA.

Results There were 6 responders and 5 non-responders. The responders showed a significantly lower serum level of chemokine (C-C motif) ligand 4/macrophage inflammatory protein-1β (CCL4/MIP-1β) at baseline compared to the non-responders. Receiver operating characteristic curves to distinguish responders from non-responders using the baseline serum CCL4/MIP-1β level showed a good area under the curve of 0.9. The non-responders showed a significant increase in the level of CCL4/MIP-1β after 4 weeks compared to the baseline.

Conclusion A low baseline serum CCL4/MIP-1β level may be useful for predicting a good mepolizumab response in severe eosinophilic asthma.

Objective This case series aimed to investigate the clinical and pathological characteristics of persistent postural perceptual dizziness (PPPD).

Methods We retrospectively examined the medical records of patients with chronic dizziness in our department, and tracked the percentage of PPPD, the age and sex, disorder duration, exacerbating factors for dizziness, and duration of momentary worsening dizziness. We also examined the duration of momentary worsening dizziness in cases of depression, anxiety disorder, and somatic symptom disorder.

Results Among 229 patients with chronic dizziness, 14.4% (33/229) met the diagnostic criteria for PPPD. PPPD was the second most common disorder of patients with chronic dizziness after depression. The median age of patients with PPPD was 75 (75.8% female) and the median duration of the disorder was 60 months (range: 3-360 months). The exacerbating factors were motion without regard to direction or position (90.9%), upright posture (66.7%), and exposure to moving visual stimuli or complex visual patterns (30.3%). While the duration of momentary worsening dizziness was less than 10 minutes in 93.9% of patients with PPPD, the duration in patients with depression, anxiety disorder, and somatic symptom disorder were 3.6 % (2/55), 16.1% (5/31), and 0% (0/11), respectively. When the duration was less than 10 minutes, the odds ratios of PPPD for depression and anxiety disorder were 46.5 (95% CI: 6.1-362.0) and 40.3 (95% CI: 7.4-219.3), respectively.

Conclusion Short episodes of momentary worsening dizziness constitute a distinctive feature of PPPD that may be useful for differentiating PPPD from other types of psychogenic dizziness.

Objective Kampo is a traditional Japanese medicine using formulae of natural agents. Although Kampo is widely practiced, information regarding the current prescriptions of Kampo formulations is lacking. The aim of the study was to describe the outpatient use of Kampo formulations in the current Japanese health insurance system.

Methods From the JMDC Claims Database, we identified subscribers with outpatient prescriptions of Kampo extract formulations between April 2017 and March 2018. Prescription records were summarized at the individual level to describe the pattern of each formula's use, such as the frequency of prescription and the number of days within a year that were covered by the prescriptions. We also examined whether or not Kampo formulations were prescribed in combination with other drugs.

Results Of the 4.5 million subscribers, 13.5% received prescriptions of Kampo extracts within 1 year, and 54% of Kampo users were women. The most commonly prescribed Kampo formulae included kakkonto, shoseiryuto, and maoto, which were used for the short term covering a median of 5 to 7 days. There were also several formulae that were prescribed for longer periods. The median numbers of days covered by kamishoyosan and keishibukuryogan were 60 and 56, respectively. Kampo formulations were used in combination with Western drugs in 85% of prescriptions.

Conclusion Kampo formulations are commonly prescribed under the Japanese insurance system and are frequently used in combination with Western drugs. The pattern of prescriptions varied across different formulae.

A 47-year-old man presented with dysgeusia, anorexia, and diarrhea. An endoscopic evaluation showed widespread gastrointestinal nodular inflammation and polyps. The pathological findings were consistent with Cronkhite-Canada Syndrome (CCS). Prednisolone therapy resulted in clinical improvement. However, CCS relapse complicated with gastric obstruction was observed during drug tapering. Although his symptoms disappeared after the reintroduction of steroids, he developed membranous nephritis. Additional cyclosporine A (CyA) treatment dramatically improved his proteinuria and residual gastrointestinal polyposis. The clinical symptoms resolved with steroid treatment, while CyA was effective for both CCS lesions and membranous nephropathy. CyA might therefore be a potential treatment option for CCS associated with membranous nephropathy.

A 66-year-old Japanese man was referred to our hospital with multiple giant liver cysts. The cysts had already been detected as multiple 3-cm cysts with small nodules at another hospital 12 years prior to this presentation. The cysts were diagnosed as an intraductal papillary neoplasms of the bile duct (IPNB) occupying the right lobe of the liver. Extended right lobectomy was performed. Based on the pathological findings, the tumor was diagnosed to be an oncocytic-type IPNB with minimal invasion. This experience suggests that the progression of IPNBs occur relatively slowly. The present case might provide important information for understanding the natural history of IPNBs.

A 70-year-old man was admitted to our hospital with gait disturbance due to marked edema of the lower limbs for more than 6 months. He had been receiving systemic chemotherapy over two years for multiple recurrence after sigmoid colon cancer resection. Contrast-enhanced computed tomography demonstrated severe inferior vena cava (IVC) stenosis due to compression by lymph node metastases, i.e. IVC syndrome. As increased doses of diuretic agents failed to improve the edema, IVC stent placement was performed. This led to significant improvement of the edema and complete gait normalization. This case demonstrates the efficacy of IVC stent placement for IVC syndrome.

A 51-year-old woman who presented with a large cystic liver tumor with mural nodules in the lateral segment developed Trousseau's syndrome. A mural nodule directly invaded her liver parenchyma. Metastatic nodules were detected in the right lobe and portal/paraaortic lymph nodes. The pathological findings showed mucin-producing adenocarcinoma cells to have invaded the fibrous stroma forming a micropapillary cluster. She developed obstructive jaundice due to tumor progression and subsequently died of hepatic failure. Invasive biliary mucinous cystic neoplasm (MCN) is a rare form of a malignant tumor with a relatively favorable prognosis. This is a very rare case biliary MCN with invasive carcinoma that showed intrahepatic and lymph node metastases.

Inferior vena cava (IVC) anomalies, such as the absence of an intra-hepatic IVC or IVC hypoplasia, are rare. Usually, these anomalies are asymptomatic and cause few clinical issues. We herien report a 53-year-old woman with IVC anomalies who demonstrated both azygos and portal vein system continuation. Over time, this resulted in gradually progressive portal hypertension due to abnormal hemodynamics. The increased inflow from the IVC to the portal vein system for an extended time may contribute to the development of portal hypertension without liver cirrhosis.

Severe coronavirus disease (COVID-19) can induce serious complications, including acute respiratory distress syndrome, septic shock, and acute kidney injury. However, few reports have associated COVID-19 with pancreatitis. We herein report the case of a 55-year-old patient who developed acute pancreatitis associated with severe COVID-19 pneumonia and was successfully treated with veno-venous extracorporeal membrane oxygenation (ECMO). Elevated pancreatic enzymes levels and computed tomography findings led to the diagnosis of acute pancreatitis due to COVID-19. Although we found that severe COVID-19 pneumonia can lead to pancreatitis, the underlying pathophysiology remains unknown.

Alagille syndrome is an inherited multisystemic disorder. We herein report an atypical case of a Japanese adult patient with Alagille syndrome. He had been diagnosed with Alagille syndrome as an infant based on a liver biopsy. At 27 years of age, he needed to start hemodialysis therapy, but an arteriovenous fistula was not created because his peripheral blood vessels were too narrow. He also had a recurrent brain infarction due to cerebral vascular stenosis. Alagille syndrome is generally recognized as a pediatric hepatic disease, but general physicians should be aware of its potential existence with renal involvement and vascular abnormalities.

Acute eosinophilic pneumonia (AEP) is an acute respiratory illness with diffuse pulmonary infiltrates and pulmonary eosinophilia. While the etiology of AEP remains unclear, a relationship between cigarette smoking and AEP onset has been suggested. The use of heated tobacco products (HTPs) has been growing, but the impact of these products on our health is not fully understood. We herein report a case of AEP that developed after switching from conventional cigarette to HTP smoking. The patient's condition improved after the cessation of HTP smoking and corticosteroid treatment initiation. In cases of AEP, physicians should consider HTPs use as a possible cause.

A 73-year-old woman was admitted to our hospital for treatment of vomiting. Four months previously, she had been diagnosed with lung adenocarcinoma (cT3N3M1a stage IVA) and started receiving afatinib as first-line treatment. On admission, the primary tumor had shrunk, but abdominal computed tomography revealed a new retroperitoneal lesion causing duodenal obstruction and hydronephrosis. She underwent gastrojejunostomy, and a biopsy of the peritoneum revealed adenocarcinoma. She was treated with second-line chemotherapy but developed cerebral infarction and died 104 days after admission. An autopsy revealed marked fibrosis with scattered tumor cells in the retroperitoneum. The underlying mechanism of the metastasis is discussed.

Coronavirus disease 2019 (COVID-19) has been recognized as a worldwide pandemic. However, the clinical course of COVID-19 remains poorly characterized. Although some cases of pneumothorax have been reported, they all had pulmonary complications or were managed with mechanical ventilation. We herein report a case of pneumothorax that developed even though the patient had no pulmonary underlying diseases and had never been managed with mechanical ventilation. In the present case, a lung bulla was found on chest computed tomography during treatment for COVID-19. We concluded that COVID-19 affected the formation of the lung bulla and induced the complication of pneumothorax.

Tocilizumab (TCZ; Actemra/RoActemra) is an anti-interleukin (IL)-6 receptor antibody for the treatment of rheumatoid arthritis (RA) and other autoimmune diseases and cytokine storms. The present case is a 63-year-old female well-controlled RA patient, who presented with a progressive cognitive impairment after 34 months of TCZ administration. Brain magnetic resonance imaging (MRI) showed leukencephalopathy with a lactic acid peak in magnetic resonance spectroscopy (MRS), a decreased blood flow in single photon emission computed tomography (SPECT), and a decreased accumulation in fluorodeoxyglucose positron emission tomography (FDG-PET). The discontinuation of TCZ improved her cognitive function and brain MRI findings at 3 months after drug cessation. The present case suggests that TCZ may sometimes cause leukoencephalopathy after long-term administration, and thus the early discontinuation of TCZ is recommended to achieve a good prognosis.

A 78-year-old woman in complete remission of mass-forming primary central nervous system lymphoma (PCNSL) showed diffuse leukoencephalopathy as well as corticospinal tract lesions with intense gadolinium enhancement on magnetic resonance imaging (MRI). She died 3 months later. In line with the MRI findings, pathological examination revealed dense infiltration of atypical lymphoid cells, consistent with a diagnosis of lymphomatosis cerebri (LC)-type PCNSL. This is the first report of LC in which the corticospinal tracts demonstrated robust contrast enhancement directly corresponding to the neuropathological findings, and it is also a rare instance in which LC presented as a recurrence of typical PCNSL.

Leuconostoc lactis, often found in fermented dairy products, although considered to have a low pathogenic potential, can cause life-threatening infections in immunocompromised hosts. We herein report a 62-year-old man with a history of alcoholic liver cirrhosis, hepatocellular carcinoma, and diabetes mellitus who developed a very rare case of bacterial meningitis caused by this organism. After we administered antibiotics including ampicillin, he recovered completely within two weeks. This gram-positive coccus (GPC) is sensitive to ampicillin but naturally resistant to vancomycin, while its susceptibility to ceftriaxone has not yet been established. In acute GPC meningitis in immunocompromised hosts, Leuconostoc lactis should therefore be considered as a possible pathogen.

A 9-year-old female reported left-sided, excruciatingly severe, stabbing orbital pain with cranial autonomic symptoms. The attacks continued for 1 year with a remission period of 2 months. Each attack duration was approximately 120 minutes with a frequency of two to three times a day. The patient was diagnosed with chronic cluster headache (CCH) according to the third edition of the International Classification of Headache Disorders. A combination of low-dose verapamil and lomerizine once a week decreased the frequency of the attacks, and oral sumatriptan became an effective abortive therapy. No case reports of pediatric CCH have been previously published in Japan.

A 21-year-old man presented with the chief complaints of fever and sore throat after visiting Cambodia and Thailand. Computed tomography revealed multiple pulmonary nodules. After performing antibiotic therapy, the pulmonary nodules without bacteremia disappeared completely. Paired microscopic agglutination tests revealed seroconversion against Leptospira serogroup Autumnalis. Thus, he was diagnosed with multiple pulmonary nodules caused by leptospirosis. Leptospirosis is a common zoonosis that occurs in tropical and subtropical areas. Its various clinical features include unspecified fever and Weil's disease. Although diffuse alveolar hemorrhaging is known to occur in severe leptospirosis, multiple pulmonary nodules resembling septic emboli or vasculitis are a rare complication.

Treatment with tocilizumab (TCZ) to block interleukin-6 (IL-6) signalling is predicted to mitigate cytokine release syndrome (CRS) caused by coronavirus disease 2019 (COVID-19). However, the adverse effects of TCZ on patients with COVID-19 remain unclear. We herein report a patient with COVID-19 treated with TCZ who developed acute hypertriglyceridaemia. Despite favipiravir treatment, acute respiratory distress syndrome developed in a 45-year-old patient with COVID-19; thus, TCZ was initiated. The triglyceride levels greatly increased after TCZ administration. Physicians should consider the negative impact of TCZ on the lipid profile in patients with COVID-19, although COVID-19-induced CRS itself may be an aggravating factor.

We herein report the first case of a fever induced by favipiravir, a potential coronavirus disease 2019 therapeutic drug. An 82-year-old man diagnosed with bilateral pneumonia was transferred to our hospital following a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test. He was treated with compassionate use of favipiravir. Both his oxygen demand and fever gradually improved after admission; however, his fever relapsed, and the C-reactive protein (CRP) levels increased on day 7. We diagnosed his fever as being favipiravir-induced. The fever resolved a few days after favipiravir discontinuation, demonstrating the accuracy of the diagnosis. This case revealed that favipiravir can induce a fever.

Arterial and venous thrombi can coexist without preexisting conditions, such as malignant disease, thrombotic predisposition, or arteriovenous shunt. We herein report a case of acute cerebral infarction and pulmonary thromboembolism in the absence of underlying disease. A 71-year-old woman presented with left hemiplegia. On an examination, her oxygen saturation was 91% on ambient air despite the absence of chest symptoms and clear lung fields on a chest radiograph. The patient was finally diagnosed with acute cerebral infarction caused by large artery atherosclerosis and acute pulmonary thromboembolism due to deep vein thrombosis, consequent to immobilization for three days after the onset of cerebral infarction.