Publications by authors named "Masayuki Ota"

35 Publications

Clinicopathological and Genomic Features of Pediatric Intracranial Myxoid Mesenchymal Tumor with both of Gene Fusion and Mutation: A Case Report and Comparison with Adult Cases in the Literature.

NMC Case Rep J 2022 18;9:101-109. Epub 2022 May 18.

Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan.

Intracranial myxoid mesenchymal tumors (IMMTs) with family gene fusion are rare brain neoplasms characterized by gene fusion between the gene and one of the cyclic AMP response element-binding (CREB) family transcription factor (, , or ) genes. Although half of reported cases are pediatric, the clinical, histologic, and genomic features of IMMTs with rearrangement in pediatric populations are not yet well clarified. Here we describe the case of a 7-year-old girl who presented with seizures due to an extra-axial tumor in the left parietal convexity. Gross total resection was achieved, and the tumor displayed a multilobular structure with solid hypercellular and myxoid hypocellular areas, separated by a variable amount of stroma. The hypercellular areas consisted of round to polygonal cells, whereas the myxoid areas were ovoid to spindled cells. Immunophenotypically, the tumor cells were positive for vimentin, desmin, and EMA. Next-generation sequencing of tumoral DNA revealed gene fusion and a pathogenic mutation of . No recurrence was detected 9 months after resection, without chemotherapy or radiotherapy. In comparison to other pediatric and adult patients with rearrangement, many clinical, radiological, and immunohistochemical features were shared. However, signs of elevated intracranial pressure were more frequently observed, and postoperative radiation was less frequently administered for pediatric patients. Gross total resection (GTR) was the key prognostic factor for better disease control especially among pediatric patients. Further reports of cases with rearrangement with detailed genetic profiles are essential for clarifying the oncogenic pathway and establishing a standard treatment strategy.
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http://dx.doi.org/10.2176/jns-nmc.2021-0385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177164PMC
May 2022

Nosocomial outbreak of coronavirus disease in two general wards during the initial wave of the pandemic in 2020, 
Tokyo, Japan.

Western Pac Surveill Response J 2022 Jan-Mar;13(1):1-5. Epub 2022 Mar 24.

Department of Infectious Diseases, Tokyo Metropolitan Bokutoh General Hospital, Tokyo, Japan.

Objective: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in China and subsequently spread worldwide. In Japan, many clusters occurred during the first wave in 2020. We describe the investigation of an early outbreak in a Tokyo hospital.

Methods: A COVID-19 outbreak occurred in two wards of the hospital from April to early May 2020. Confirmed cases were individuals with laboratory-confirmed SARS-CoV-2 infection linked to Wards A and B, and contacts were patients or workers in Wards A or B 2 weeks before the index cases developed symptoms. All contacts were tested, and cases were interviewed to determine the likely route of infection and inform the development of countermeasures to curb transmission.

Results: There were 518 contacts, comprising 472 health-care workers (HCWs) and 46 patients, of whom 517 were tested. SARS-CoV-2 infection was confirmed in 42 individuals (30 HCWs and 12 patients). The proportions of SARS-CoV-2 infections in HCWs were highest among surgeons, nurses, nursing assistants and medical assistants. Several HCWs in these groups reported being in close proximity to one another while not wearing medical masks. Among HCWs, infection was thought to be associated with the use of a small break room and conference room.

Discussion: Nosocomial SARS-CoV-2 infections occurred in two wards of a Tokyo hospital, affecting HCWs and patients. Not wearing masks was considered a key risk factor for infection during this outbreak; masks are now a mandated countermeasure to prevent the spread of SARS-CoV-2 infection in hospital settings.
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http://dx.doi.org/10.5365/wpsar.2022.13.1.906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016264PMC
May 2022

Enhanced event-based surveillance for imported diseases during the Tokyo 2020 Olympic and Paralympic Games.

Western Pac Surveill Response J 2021 Oct-Dec;12(4):1-7. Epub 2021 Dec 22.

Center for Emergency Preparedness and Response, National Institute of Infectious Diseases, Tokyo, Japan.

In 2021, the National Institute of Infectious Diseases, Japan, undertook enhanced event-based surveillance (EBS) for infectious diseases occurring overseas that have potential for importation (excluding coronavirus disease 2019 [COVID-19]) for the Tokyo 2020 Olympic and Paralympic Summer Games (the Games). The pre-existing EBS system was enhanced using the World Health Organization Epidemic Intelligence from Open Sources system and the BlueDot Epidemic Intelligence platform. The enhanced EBS before and during the Games did not detect any major public health event that would warrant action for the Games. However, information from multiple sources helped us identify events, characterize risk and improve confidence in risk assessment. The collaboration also reduced the surveillance workload of the host country, while ensuring the quality of surveillance, even during the COVID-19 pandemic.
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http://dx.doi.org/10.5365/wpsar.2021.12.4.903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8873917PMC
March 2022

Exploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment.

JGH Open 2021 Nov 1;5(11):1266-1274. Epub 2021 Oct 1.

Department of Diagnostic Pathology, Graduate School of Medicine Chiba University Chiba Japan.

Background And Aim: Immune checkpoint inhibitors and their combination with other agents have recently been available in advanced hepatocellular carcinoma (HCC). Hence, a thorough understanding of the tumor microenvironment based on tumor samples is yet to be achieved. This study aimed to explore the tumor microenvironment in advanced HCC in terms of microsatellite instability-high (MSI-H) by using tumor samples from advanced HCC patients eligible for systemic therapy.

Methods: MSI-H was assessed by polymerase chain reaction, and the expression of mismatch repair proteins, PD-L1, CD8, VEGF, and HLA-class1 was evaluated by immunohistochemistry. Whole-exome sequencing was performed for MSI-H tumor samples.

Results: Of 50 patients, one (2.0%) was confirmed with MSI-H. In the MSI-H advanced HCC tumor, a high tumor mutation burden, infiltration of CD8 lymphocytes, and low expression of VEGF were identified. Although PD-L1 expression was negative, there was shrinkage of tumor following pembrolizumab. However, another tumor nonresponsive to pembrolizumab was present simultaneously. Checking the Cancer Genome Atlas (TCGA) database, we found a similar case to this patient. The TCGA case had unique gene features of miR-21 and miR-155 overexpression and hypermethylation of the gene.

Conclusion: We identified a very small number of MSI-H cases in HCC using one tumor biopsy sample for each patient with advanced HCC. In addition, epigenetic aberrations possibly lead to MSI-H in HCC patients. Since different HCC clones might coexist in the liver, sampling from multiple tumors should be considered to clarify the true proportion of MSI-H in HCC and to analyze tumor microenvironments.
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http://dx.doi.org/10.1002/jgh3.12660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593775PMC
November 2021

Extracorporeal membrane oxygenation may decrease the plasma concentration of remdesivir in a patient with severe coronavirus disease 2019.

IDCases 2021 17;26:e01343. Epub 2021 Nov 17.

Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan.

Remdesivir is an antiviral drug that results in clinical improvement after five days of treatment and accelerates recovery by 31%. No studies have discussed the pharmacokinetic analysis of remdesivir in patients with severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO). A 63-year-old American man who underwent mechanical ventilation and ECMO for severe COVID-19 was administered remdesivir for ten days. The loading dosage was 200 mg at 7 PM on day 12 and 100 mg daily at 0:00 PM from day 13-21, administered within 1 h. The pharmacokinetic analysis was performed. The serum creatinine concentration was within the normal range of 0.5-0.7 mg/dL during treatment. According to the pharmacokinetic analysis, the plasma concentrations of remdesivir and GS-441524 4 h after administration (C) were 662 ng/mL and 58 ng/mL, respectively, and the concentrations 18 h after administration (C) were 32 ng/mL and 44 ng/mL, respectively. Therefore, the half-life of remdesivir and GS-441524 was 3.2 and 35.1 h, respectively. Monitoring the plasma concentrations of remdesivir and GS-441524 in patients undergoing ECMO may be necessary.
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http://dx.doi.org/10.1016/j.idcr.2021.e01343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596653PMC
November 2021

Henoch-Schonlein Purpura After Cardiac Device Removal for Staphylococcus Aureus Infective Endocarditis.

Circ J 2022 03 16;86(4):722. Epub 2021 Nov 16.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine.

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http://dx.doi.org/10.1253/circj.CJ-21-0772DOI Listing
March 2022

Genetic profiles of Barrett's esophagus and esophageal adenocarcinoma in Japanese patients.

Sci Rep 2021 09 3;11(1):17671. Epub 2021 Sep 3.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba, 260-8670, Japan.

The genetic characteristics of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) in the Japanese population is unclear. This study aims to investigate the genetic characteristics from nondysplastic BE (NDBE) to early EAC in Japan. Clinical information was collected. Moreover, the genetic profile of NDBE without concurrent dysplasia, early EAC, and surrounding BE were also investigated using endoscopic biopsy samples and formalin-fixed, paraffin-embedded specimens from Japanese patients by targeted next-generation sequencing. Immunohistochemical staining for p53 was also performed for EAC lesions. Targeted NGS was performed for 33 cases with 77 specimens. No significant difference exists in the NDBE group between the number of putative drivers per lesion in the short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE) [0 (range, 0-1) vs. 0 (range, 0-1). p = 1.00]. TP53 putative drivers were found in two patients (16.7%) with nondysplastic SSBE. TP53 was the majority of putative drivers in both BE adjacent to EAC and EAC, accounting for 66.7% and 66.7%, respectively. More putative drivers per lesion were found in the EAC than in the NDBE group [1 (range, 0-3) vs. 0 (range, 0-1). p < 0.01]. The genetic variants of TP53 in the Japanese early EAC were similar to those in western countries. However, TP53 putative drivers were detected even in Japanese patients with nondysplastic SSBE. This is significant because such nondysplastic SSBE might have higher risk of progressing to high-grade dysplasia or EAC. The risks of progression may not be underestimated and appropriate follow-ups may be necessary even in patients with SSBE.Trial registration: This study was registered at the University Hospital Medical Information Network (UMIN000034247).
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http://dx.doi.org/10.1038/s41598-021-97249-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417273PMC
September 2021

Environmental surface and air contamination in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patient rooms by disease severity.

Infect Prev Pract 2020 Dec 13;2(4):100098. Epub 2020 Oct 13.

Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan.

Background: The coronavirus disease 2019 (COVID-19) continues to spread around the world. In addition to community-acquired infections, nosocomial infections are also a major social concern. The likelihood of environmental contamination and transmission of the virus based on disease severity is unknown.

Methods: We collected nasopharyngeal, environmental and air samples from patients with COVID-19 admitted to the National Centre for Global Health and Medicine between January 29 and February 29, 2020. The patients were classified by severity of disease. The collected samples were tested using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcription polymerase chain reaction (real-time RT-PCR).

Results: SARS-CoV-2 was not detected in a subset of 11 air samples. Of the 141 environmental samples collected from three patient bays and two single rooms, four samples tested positive for SARS-CoV-2 by real-time RT-PCR. Detections were made on the surface of a stethoscope used in the care of a patient with severe disease, on the intubation tube of a patient classified as critical (and on ventilator management), and on the surface of a gown worn by the nurse providing care.

Conclusions: Regardless of the patients' disease severity, SARS-CoV-2 was detected on very few environmental surfaces. However, detection of SARS-CoV-2 on stethoscopes used in the care of multiple patients and on the surface of gowns worn by clinical staff indicates that medical devices may be linked to the spread of infection.
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http://dx.doi.org/10.1016/j.infpip.2020.100098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550981PMC
December 2020

Safety of Diphtheria and Tetanus Toxoids and Acellular Pertussis (DTaP) Vaccine in Adults in Japan.

Jpn J Infect Dis 2021 Sep 29;74(5):399-404. Epub 2021 Jan 29.

Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan.

Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is generally used for booster vaccination of infants in Europe and the United States to avoid increased reactogenicity after diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccination. However, Japan has extended the use of additional DTaP vaccination without reducing the antigen dose for diphtheria and pertussis in adolescents and adults, despite limited reports on its safety in adults. This prospective, observational, questionnaire-based study investigated the occurrence of adverse events (AEs) following DTaP vaccination between June 2018 and June 2019 in participants aged 10 years or older. Of the 250 eligible participants, 235 (94%) responded regarding AEs. Among them, 133 (56.6%) reported AEs, of which 39 reported systemic AEs (16.6%) and 120 reported local AEs (51.1%) attributed to DTaP vaccination. The incidence of local AEs was markedly higher with DTaP vaccination than with non-DTaP vaccination (51.1% vs. 10.5%), and AEs appeared later (P < 0.01) and lasted longer (P < 0.01) with DTaP vaccination. However, more than 75% of these AEs resolved within 7 days. DTaP vaccination was not associated with any serious AEs. These results indicate that the DTaP vaccine can be widely used as a booster in adults as an alternative to the Tdap vaccine.
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http://dx.doi.org/10.7883/yoken.JJID.2020.947DOI Listing
September 2021

COVID-19 can suddenly become severe: a case series from Tokyo, Japan.

Glob Health Med 2020 Jun;2(3):174-177

Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan.

Since the initial report of coronavirus disease (COVID-19) from the City of Wuhan, China in December 2019, there have been multiple cases globally. Reported here are 11 cases of COVID-19 at this hospital; all of the patients in question presented with relative bradycardia. The severity of the disease was classified into four grades. Of the patients studied, 3 with mild COVID-19 and 3 with moderate COVID-19 improved spontaneously. Lopinavir/ ritonavir was administered to 3 patients with severe COVID-19 and 2 with critical COVID-19. Both patients with critical COVID-19 required mechanical ventilation and extracorporeal membrane oxygenation. Both patients with critical COVID-19 had a higher fever that persisted for longer than patients with milder COVID-19. The respiratory status of patients with critical COVID-19 worsened rapidly 7 days after the onset of symptoms. Relative bradycardia may be useful in distinguishing between COVID-19 and bacterial community-acquired pneumonia. In patients who have had a fever for > 7 days, the condition might worsen suddenly.
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http://dx.doi.org/10.35772/ghm.2020.01054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731267PMC
June 2020

SARS-CoV-2 infection among returnees on charter flights to Japan from Hubei, China: a report from National Center for Global Health and Medicine.

Glob Health Med 2020 Apr;2(2):107-111

Department of Infectious Diseases, Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan.

Due to the significant spread of a new type of coronavirus (SARS-CoV-2) infection (COVID-19) in China, the Chinese government blockaded several cities in Hubei Province. Japanese citizens lost a means of transportation to return back to Japan. The National Center for Global Health and Medicine (NCGM) helped the operation of charter flights for evacuation of Japanese residents from Hubei Province, and this article outlines our experiences. A total of five charter flights were dispatched, and the majority of returnees (793/829 [95.7%]) were handled at NCGM. A large number of personnel from various departments participated in this operation; 107 physicians, 115 nurses, 110 clerical staff, and 45 laboratory technicians in total. Several medical translators were also involved. In this operation, we conducted airborne precautions in addition to contact precautions. Eye shields were also used. The doctors collecting the pharyngeal swab used a coverall to minimize the risk of body surface contamination from secretions and droplets. Enhanced hand hygiene using alcohol hand sanitizer was performed. Forty-eight persons were ultimately hospitalized after the triage at NCGM operation, which was more than the number of persons triaged at the airport ( = 34). Of those hospitalized after NCGM triage, 8.3% (4/48 patients) ultimately tested positive for SARS-CoV-2, significantly higher than the positive rate among subjects not triaged (4/48 [8.3%] 9/745 [1.2%]: = 0.0057). NCGM participated in a large-scale operation to evacuate Japanese nationals from the COVID-19 epidemic area. We were able to establish a scheme through this experience that can be used in the future.
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http://dx.doi.org/10.35772/ghm.2020.01036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731067PMC
April 2020

Non-COVID-19 Patients with Life-threatening Diseases Who Visited a Fever Clinic: A Single-center, Observational Study in Tokyo, Japan.

Intern Med 2020 Dec 2;59(24):3131-3133. Epub 2020 Nov 2.

Department of Infectious Diseases, Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan.

Objective In fever clinics screening coronavirus disease (COVID-19), there could be patients with life-threatening diseases that physicians should not overlook. We exploratorily investigated the final diagnosis among non-COVID-19 hospitalized patients who visited the fever clinic. Methods This was a retrospective, observational, and single-centered study conducted in the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. We conducted a retrospective chart review of patients who visited the fever clinic in the NCGM from 11 March 2020 to 24 April 2020. Patients Patients who met the following clinical criteria visited the fever clinic in the NCGM: (1) body temperature >37.5°C, (2) any symptoms consistent with COVID-19 or (3) referral from local healthcare facilities. In the fever clinic, all patients who met the above criteria had severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test with nasopharyngeal swab specimens. Patients with severe symptoms or an unstable condition were sent to an outpatient clinic for infectious diseases for further evaluation and treatment. Results Among 1,470 patients who visited the fever clinic, 84 patients were hospitalized, and 45 of them were diagnosed as having COVID-19. Among the remaining 39 non-COVID-19 patients, there were nine patients with life-threatening diseases. The life-threatening diseases included acute heart failure, septic shock, pneumocystis pneumonia, peritonsillar abscess, and necrotizing fasciitis. Conclusion Physicians should evaluate each patient carefully while considering other life-threatening conditions even in such a COVID-19 pandemic era.
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http://dx.doi.org/10.2169/internalmedicine.5614-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807116PMC
December 2020

Effectiveness of personal protective equipment in preventing severe acute respiratory syndrome coronavirus 2 infection among healthcare workers.

J Infect Chemother 2021 Jan 9;27(1):120-122. Epub 2020 Sep 9.

Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan; Emerging and Re-emerging Infectious Diseases, Graduate School of Medicine, Tohoku University, Sendai, Japan.

Introduction: Information on the effectiveness of personal protective equipment (PPE) for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers (HCWs), especially among HCWs with frequent contact with patients with SARS-CoV-2, is limited.

Methods: We conducted a prospective cohort study on 49 HCWs who worked in close contact with patients with SARS-CoV-2 infection. HCWs had blood samples taken every 2 weeks to test for SARS-CoV-2 antibodies using two different types of assay.

Results: Forty-nine participants (31 nurses, 15 doctors, 3 other workers) were enrolled. In total, 112 blood samples are obtained from participants. The median work days in 2 weeks was 9 (interquartile range (IQR): 5-10) days. In a single work day, 30 of the 49 participants (61.5%) had contact with patients with suspected or conformed SARS-CoV-2 at least 8 times, and approximately 60% of participants had more than 10 min of contact with a single patient. The median self-reported compliance to PPE was 90% (IQR: 80-100%). Seven participants tested positive for SARS-CoV-2 antibody using enzyme-linked immunosorbent assay (ELISA); however, none were seropositive for SARS-CoV-2 neutralizing antibody, so the positive ELISA results were assumed to be false-positive.

Conclusions: The study provides evidence that appropriate PPE is sufficient to prevent infection amongHCWs. It is necessary to establish a system that provides a stable supply of PPE for HCWs to perform their duties.
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http://dx.doi.org/10.1016/j.jiac.2020.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480255PMC
January 2021

Evaluation of Coronavirus Disease 2019 Severity Using Urine Biomarkers.

Crit Care Explor 2020 Aug 31;2(8):e0170. Epub 2020 Jul 31.

National Center Biobank Network, National Center for Global Health and Medicine, Tokyo, Japan.

Subjects: Early detection of coronavirus disease 2019 in patients likely to develop severe manifestations enables appropriate interventions, including rapid ICU admission. This study was conducted to determine whether noninvasive urine biomarkers can predict the clinical severity of coronavirus disease 2019.

Interventions: Not applicable.

Measurements And Main Results: This is single-center study, national center hospital designated for infectious disease. Fifty-eight patients who tested positive for severe acute respiratory syndrome coronavirus 2 in respiratory specimens through real-time reverse transcription-polymerase chain reaction were retrospectively studied. Urinary β2-microglobulin, liver-type fatty acid-binding protein were serially measured. Serum interferon-γ and monocyte chemotactic protein-1 were also evaluated. The 58 patients were assigned into three groups. Patients requiring intensive care were assigned to the severe group ( = 12). Patients treated with oxygen were assigned to the moderate group ( = 13). Other patients were assigned to the mild group ( = 33). Urine tests revealed that low β2-microglobulin and liver-type fatty acid-binding protein levels were associated with mild disease, whereas high levels were associated with severe disease. In severe cases, liver-type fatty acid-binding protein tended to be persistently high. The resulting cutoff values were β2-microglobulin; severe versus moderate + mild: 2,457 μg/dL (specificity 76.9% and sensitivity 90.0%, area under the receiver operating characteristic curve 85.9%), liver-type fatty acid-binding protein; severe versus moderate + mild: 22.0 μg/gCre (specificity 84.6% and sensitivity 90%, area under the receiver operating characteristic curve 91.8%). Urinary β2-microglobulin and serum interferon-γ/monocyte chemotactic protein-1 showed a similar trend.

Conclusions: Evaluating urinary biomarkers such as β2-microglobulin and liver-type fatty acid-binding protein may allow determination of coronavirus disease 2019 patients with active cytokines and recognition of patients likely to become critically ill and requiring careful observation and early intervention.
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http://dx.doi.org/10.1097/CCE.0000000000000170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402421PMC
August 2020

SARS-CoV-2 Screening Test for Japanese Returnees From Wuhan, China, January 2020.

Open Forum Infect Dis 2020 Jul 20;7(7):ofaa243. Epub 2020 Jun 20.

Department of Infectious Diseases, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, Japan.

Background: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) was found to be the causative microorganism of coronavirus disease 2019 (COVID-19), which started to spread in Wuhan, China. This study was to evaluate the effectiveness of questionnaire, symptoms-based screening, and polymerase chain reaction (PCR) screening of returnees from COVID-19-endemic areas on a chartered flight, to examine the proportion of infected persons and the proportion of asymptomatic persons among infected persons who returned from Wuhan.

Methods: A retrospective cohort study was done in 7 tertiary medical institutions in Japan. A total of 566 Japanese who returned from Wuhan participated in the study.

Results: Overall, 11 of the 566 passengers had a positive SARS-CoV-2 PCR result for pharyngeal swabs and 6 were asymptomatic. Only fever differed between SARS-CoV-2-positive and -negative individuals ( < .043). Six of the 11 PCR-positive individuals were asymptomatic; 4 remained positive on day 10, and 1 asymptomatic person tested positive up to day 27. Two of the 11 were negative on the first PCR test and positive on the second.

Conclusions: Our results will be important insights on screening returnees from locked-down cities, as well as providing important data on the proportion of asymptomatic individuals infected with SARS-CoV-2. A 13-day observation period and a second round of PCR may be effective to screen patients, including asymptomatic infections.
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http://dx.doi.org/10.1093/ofid/ofaa243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337761PMC
July 2020

Dengue Virus Serotype 1 Exported to Japan from Côte d'Ivoire, 2019.

Jpn J Infect Dis 2021 Mar 1;74(2):148-150. Epub 2020 Aug 1.

Department of Infectious Diseases, Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan.

Dengue fever outbreaks have been repeatedly reported in Côte d'Ivoire. During the 2019 outbreak, DENV-1 was the predominant strain and phylogenetic analysis of the DENV-1 genome obtained from the present patient who returned to Japan in January 2019 revealed a high homology with the 2013-2014 Southeast Asian strains. In a previous outbreak in 2017, DENV-1 accounted for 5% of the DENV serotypes. The endemic DENV-1 strain in Abidjan in 2019 could be a strain that was imported from Southeast Asia. Dengue virus can spread globally, and imported dengue fever cases could serve as an alert for outbreaks in the exporting country.
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http://dx.doi.org/10.7883/yoken.JJID.2019.303DOI Listing
March 2021

Androgenetic Complete Hydatidiform Moles With p57KIP2-Positive Immunostaining.

Am J Clin Pathol 2020 11;154(6):776-783

Departments of Reproductive Medicine, Chiba, Japan.

Objectives: Complete hydatidiform moles (CHMs) are androgenetic and have a high rate of progression to gestational trophoblastic neoplasia (GTN). CHMs are negative when immunostained for p57KIP2 protein, the product of the maternally expressed gene on chromosome 11p15.5, whereas biparental partial hydatidiform moles and hydropic abortion are positive for p57KIP2. This study presents two cases of p57KIP2-positive androgenetic CHMs and explores the cause of this inconsistency.

Methods: Androgenetic CHMs were diagnosed using multiplex short tandem repeat polymorphism analysis. Single-nucleotide polymorphism arrays were performed for molecular karyotyping.

Results: Among the consecutive 188 androgenetic CHMs, two cases were positive for p57KIP2. The first case remitted spontaneously, whereas the second case developed into low-risk GTN. The first case was positive for p57KIP2 in all villi. The karyotype was 48,XX,+7,+11, with the additional chromosome 11 confirmed to be of maternal origin. The second case presented a mosaic of both positively and negatively stained villi. The karyotype was 46,XX.

Conclusions: The cause of one of the CHMs was trisomy with an additional maternal chromosome 11. Although rare, the confirmation of p57KIP2-positive androgenetic CHM status is necessary to manage GTN risk.
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http://dx.doi.org/10.1093/ajcp/aqaa096DOI Listing
November 2020

Androgenetic Complete Hydatidiform Moles With p57KIP2-Positive Immunostaining.

Am J Clin Pathol 2020 11;154(6):776-783

Departments of Reproductive Medicine, Chiba, Japan.

Objectives: Complete hydatidiform moles (CHMs) are androgenetic and have a high rate of progression to gestational trophoblastic neoplasia (GTN). CHMs are negative when immunostained for p57KIP2 protein, the product of the maternally expressed gene on chromosome 11p15.5, whereas biparental partial hydatidiform moles and hydropic abortion are positive for p57KIP2. This study presents two cases of p57KIP2-positive androgenetic CHMs and explores the cause of this inconsistency.

Methods: Androgenetic CHMs were diagnosed using multiplex short tandem repeat polymorphism analysis. Single-nucleotide polymorphism arrays were performed for molecular karyotyping.

Results: Among the consecutive 188 androgenetic CHMs, two cases were positive for p57KIP2. The first case remitted spontaneously, whereas the second case developed into low-risk GTN. The first case was positive for p57KIP2 in all villi. The karyotype was 48,XX,+7,+11, with the additional chromosome 11 confirmed to be of maternal origin. The second case presented a mosaic of both positively and negatively stained villi. The karyotype was 46,XX.

Conclusions: The cause of one of the CHMs was trisomy with an additional maternal chromosome 11. Although rare, the confirmation of p57KIP2-positive androgenetic CHM status is necessary to manage GTN risk.
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http://dx.doi.org/10.1093/ajcp/aqaa096DOI Listing
November 2020

Failure of Liposomal-amphotericin B Treatment for New World Cutaneous Leishmaniasis due to Leishmania braziliensis.

Intern Med 2020 1;59(9):1227-1230. Epub 2020 May 1.

Department of Infectious Diseases, Tokyo Metropolitan Bokutoh Hospital, Japan.

Liposomal-amphotericin B (L-AmB) is used for cutaneous leishmaniasis (CL); however, its treatment failure has not yet been described in detail. A 58-year-old man returned from the Republic of Venezuela with a cutaneous ulcer on his left lower leg. The causative pathogen was Leishmania braziliensis. We started L-AmB 3 mg/kg/day for 6 days; however, the ulcer did not resolve. The patient was successfully retreated with a higher dose L-AmB 4 mg/kg/day 9 times (total, 36 mg/kg). If L-AmB fails to treat CL and other therapeutics cannot be used, increasing the L-AmB dose is a viable option.
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http://dx.doi.org/10.2169/internalmedicine.4096-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270753PMC
July 2020

Caspase recruitment domain family member 9 expression is a promising biomarker in esophageal squamous cell carcinoma.

Ann Gastroenterol Surg 2020 Mar 22;4(2):135-141. Epub 2019 Dec 22.

Department of Frontier Surgery Graduate School of Medicine Chiba University Chiba Japan.

Aim: Esophageal squamous cell carcinoma (ESCC) is a refractory digestive organ cancer that requires better treatment strategies. We have recently reported that the antidiabetic drug metformin exerts antitumor effects on ESCC by inhibition of nuclear factor kappa B (NF-κB) nuclear translocation. In the present study, we focused on caspase recruitment domain family member 9 (CARD9), an essential signal adapter in NF-κB activation to examine whether it can be used as a prognostic factor in ESCC.

Methods: We investigated CARD9 expression immunohistochemically in clinical samples obtained from 93 patients with ESCC who underwent curative esophagectomy. CARD9 expression was analyzed for correlation with clinicopathological characteristics and ESCC prognosis. The molecular effects were investigated by knocking down ESCC cells. Comprehensive RNA expression changes in these ESCC cells were detected by next-generation sequencing (NGS).

Results: High CARD9 expression is significantly correlated with advanced tumor depth ( < .001), positive lymph node metastasis ( = .005) and advanced stage ( = .001). Kaplan-Meier method and the log-rank test showed that overall survival (OS) and disease-free survival (DFS) were significantly poor in the high CARD9 expression group (OS:  = .027, DFS:  = .005). Univariate and multivariate analysis showed that high CARD9 expression is a significant poor prognostic factor for DFS. Cell proliferation and migration were suppressed by knockdown. NGS detected altered the expression of some RNAs including maternally expressed 3 ().

Conclusion: High CARD9 expression is significantly associated with poor prognosis. Therefore, CARD9 expression may be a prospective prognostic biomarker in ESCC.
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http://dx.doi.org/10.1002/ags3.12305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105841PMC
March 2020

Eight-Year Experience of Antimicrobial Stewardship Program and the Trend of Carbapenem Use at a Tertiary Acute-Care Hospital in Japan-The Impact of Postprescription Review and Feedback.

Open Forum Infect Dis 2019 Oct 5;6(10):ofz389. Epub 2019 Sep 5.

AMR Clinical Reference Center, Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan.

Objective: We implemented a stepwise antimicrobial stewardship program (ASP). This study evaluated the effect of each intervention and the overall economic impact on carbapenem (CAR) use.

Method: Carbapenem days of therapy (CAR-DOT) were calculated to assess the effect of each intervention, and antipseudomonal DOT were calculated to assess changes in use of broad-spectrum antibiotics. We carried out segmented regression analysis of studies with interrupted time series for 3 periods: Phase 1 (infectious disease [ID] consultation service only), Phase 2 (adding monitoring and e-mail feedback), and Phase 3 (adding postprescription review and feedback [PPRF] led by ID specialist doctors and pharmacists). We also estimated cost savings over the study period due to decreased CAR use.

Results: The median monthly CAR-DOT, per month per 100 patient-days, during Phase 1, Phase 2, and Phase 3 was 5.46, 3.69, and 2.78, respectively. The CAR-DOT decreased significantly immediately after the start of Phase 2, but a major decrease was not observed during this period. Although the immediate change was not apparent after Phase 3 started, CAR-DOT decreased significantly over this period. Furthermore, the monthly DOT of 3 alternative antipseudomonal agents also decreased significantly over the study period, but the incidence of antimicrobial resistance did not decrease. Cost savings over the study period, due to decreased CAR use, was estimated to be US $150 000.

Conclusions: Adding PPRF on the conventional ASP may accelerate antimicrobial stewardship. Our CAR stewardship program has had positive results, and implementation is ongoing.
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http://dx.doi.org/10.1093/ofid/ofz389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790398PMC
October 2019

Longitudinal trends of and factors associated with inappropriate antibiotic prescribing for non-bacterial acute respiratory tract infection in Japan: A retrospective claims database study, 2012-2017.

PLoS One 2019 16;14(10):e0223835. Epub 2019 Oct 16.

AMR Clinical Reference Center, National Center for Global Health and Medicine, Tokyo, Japan.

Background: Inappropriate antibiotic prescribing is a cause of antimicrobial resistance. Acute Respiratory Tract Infections (ARTI) are common diseases for those antibiotics are most likely prescribed in outpatient setting.

Objectives: To clarify factors associated with antibiotic prescribing for non-bacterial acute respiratory tract infections (NB-ARTI) and identify targets for reducing inappropriate prescribing for NB-ARTI in Japan.

Methods: We conducted a retrospective, observational study using longitudinal claims data between April 2012 and June 2017. We assessed the rate of and factors associated with inappropriate antibiotic prescribing in outpatient settings for all NB-ARTI consultations included in the database.

Results: The mean monthly antibiotic prescribing rate per 100 NB-ARTI consultations during the study period was 31.65. The monthly antibiotic prescribing rate per 100 NB-ARTI consultations decreased by 19.2% from April 2012 to June 2017. Adolescents (13-18 years) and adults of working age (19-29 and 30-39 years) were more likely prescribed antibiotics compared with elderly patients ≥ 60 years (aOR: 1.493 [95%CI: 1.482-1.503], 1.585 [95%CI: 1.575-1.595], and 1.507 [95%CI: 1.498-1.516], respectively). Outpatient clinics registered as internal medicine or ear, nose, and throat specialty were more likely to prescribe antibiotics than those of paediatric specialty or other specialties. Among health facility type, clinics without beds (aOR 2.123 [95%CI: 2.113-2.133]) and clinics with beds (aOR: 1.752 [95%CI: 1.7371-1.767]) prescribed significantly more antibiotics for NB-ARTI than outpatient departments inside general hospitals.

Conclusions: Inappropriate antibiotic prescribing for NB-ARTI is common in Japan. Although the antibiotic prescribing rate has decreased, further interventions are required to promote antimicrobial stewardship (ASP). Education and awareness for adults and promotion of ASP among physicians in clinics without beds are key drivers to reduce inappropriate antibiotic prescribing in Japan.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223835PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795458PMC
March 2020

Whole-lung pathology of pleuroparenchymal fibroelastosis (PPFE) in an explanted lung: Significance of elastic fiber-rich, non-specific interstitial pneumonia-like change in chemotherapy-related PPFE.

Pathol Int 2019 Sep 10;69(9):547-555. Epub 2019 Jul 10.

Department of Pathology, Chiba University Hospital, Chiba, Japan.

Pleuroparenchymal fibroelastosis (PPFE) is characterized by upper lobe-predominant subpleural fibroelastosis. Despite its characteristic uneven distribution, detailed whole-lung pathological features of PPFE have rarely been studied. We investigated PPFE in the explanted lungs from a 19-year-old male patient with a history of chemotherapy. Grossly, the explanted lungs showed upper lobe-predominant shrinkage with subpleural and central consolidation. Histologically, fibroelastosis was prominent in the perilobular areas and along the bronchovascular bundles. The other areas of the lung showed diffuse, non-specific interstitial pneumonia (NSIP)-like change with a characteristic increase of septal elastic fibers. In the digital image analysis, the ratio of elastic fibers to whole fibrosis (EF score) was lower in the subpleural areas than in the NSIP-like lesions, but the EF scores of the latter showed no significant difference between upper and middle/lower lobes. In the present case, the diffusely distributed elastic fiber-rich NSIP-like change, probably caused by the earlier chemotherapy, may have been conducive to the development of PPFE. This suggests that some unknown vulnerability of the upper lobe may exist, various primary lesions converging to the upper lobe predominance of PPFE.
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http://dx.doi.org/10.1111/pin.12833DOI Listing
September 2019

Helicobacter cinaedi Hepatic Cyst Infection with Bacteremia.

Emerg Infect Dis 2019 03;25(3):603-604

Helicobacter cinaedi is an enterohepatic bacillus that causes infections of various manifestations. We report a novel case of hepatic cyst infection with bacteremia caused by H. cinaedi in an immunocompetent woman in Japan. Further research is warranted to identify the epidemiologic and clinical features of H. cinaedi infection.
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http://dx.doi.org/10.3201/eid2503.180936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390758PMC
March 2019

Sclerosing pneumocytoma diagnosed by preoperative endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).

Surg Case Rep 2018 Mar 9;4(1):20. Epub 2018 Mar 9.

Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, 1-8-1, inohana, Chu-o-ku, Chiba, Chiba, Japan.

Background: Sclerosing pneumocytoma is a rare lung tumor that is usually recognized as a solitary nodule in the lung. Surgical removal is recommended; however, its clinical diagnosis is still an issue because it is difficult to differentiate from lung adenocarcinomas using a tiny sample obtained from biopsy.

Case Presentation: We report a case of pulmonary sclerosing pneumocytoma located in the upper lobe of the right lung of a 34-year-old woman, which was diagnosed before surgery by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). A 3-cm irregular mass was detected by chest X-ray without any symptoms. She was referred to our hospital after being followed for 10 years in her previous clinic. During this follow-up period, the tumor had grown to 5 cm. We performed the EBUS-TBNA for the diagnosis. The histological findings obtained by EBUS-TBNA consisted of alveolar type 2-like cells that were positive for napsin A and round cells that were positive for vimentin. Based on these immunostaining results, we successfully diagnosed sclerosing pneumocytoma before surgery. Right upper lobectomy was performed, and the pathological diagnosis of the surgical specimen was also confirmed as sclerosing pneumocytoma.

Conclusions: We herein report a case of sclerosing pneumocytoma, which was clinically diagnosed by EBUS-TBNA and resected surgically.
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http://dx.doi.org/10.1186/s40792-018-0429-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845088PMC
March 2018

The first case report of infective endocarditis caused by Gemella taiwanensis.

J Infect Chemother 2017 Aug 4;23(8):567-571. Epub 2017 Apr 4.

Department of Infectious Diseases, Tokyo Metropolitan Health and Medical Corporation Ebara Hospital, Tokyo, Japan.

Gemella is a facultative anaerobic Gram-positive coccus and a rare cause of infective endocarditis (IE). Gram staining may eventually misidentify the organism, which tends to easily decolorize and manifest as either Gram-negative or Gram-variable. Commercial biochemical tests are often used to identify Gemella, but the methods they employ sometimes lack accuracy. A 52-year-old woman was diagnosed with Gemella taiwanensis IE after initial identification of the pathogen as Gemella haemolysans using biochemical tests combined with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). She was treated successfully with penicillin, gentamicin, and mitral valve replacement. To our knowledge, this is the first case of IE confirmed by 16S rRNA gene and groEL sequencing to have been caused by G. taiwanensis. The accurate diagnosis of rare or difficult-to-identify pathogens is a major challenge for clinical microbiological laboratories. The concurrent use of molecular methods could lead to the recognition of new or different pathogens.
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http://dx.doi.org/10.1016/j.jiac.2017.02.012DOI Listing
August 2017

Vaginal Amebiasis Mimicking Cervical Cancer.

Intern Med 2016;55(20):3071-3072. Epub 2016 Oct 15.

Department of Infectious Diseases, Tokyo Metropolitan Komagome Hospital, Japan.

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http://dx.doi.org/10.2169/internalmedicine.55.7289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109583PMC
October 2016

Anterior mediastinal abscess diagnosed in a young sumo wrestler after closed blunt chest trauma.

Chin J Traumatol 2015 ;18(6):360-2

Department of Infectious Disease, Tokyo Metropolitan Bokutoh General Hospital, 4-23-15 kohtohbashi, Sumida City, Tokyo 130-0022, Japan.

Most mediastinal abscesses result from infections after thoracotomy, esophageal perforation or pene- trating chest trauma. This disease is rarely caused by closed blunt chest trauma. All previously reported such cases after closed blunt chest trauma presented with hematoma and sternal osteomyelitis resulting from sternal fracture. Here we report a 15-year-old sumo wrestler who presented with an anterior mediastinal abscess without any mediastinal fracture. The mediastinal abscess resulted from the hematogenous spread of Staphylococcus aureus to a hematoma that might have been caused by a closed blunt chest trauma incurred during sumo wrestling exercises.
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http://dx.doi.org/10.1016/j.cjtee.2015.12.002DOI Listing
December 2016
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