Publications by authors named "Toshio Naito"

158 Publications

DOCK2 is involved in the host genetics and biology of severe COVID-19.

Nature 2022 Aug 8. Epub 2022 Aug 8.

Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.

Identifying the factors underlying severe COVID-19 in the host genetics is an emerging issue. We conducted a genome-wide association study (GWAS) involving 2,393 Japanese COVID-19 cases collected in initial pandemic waves with 3,289 controls, which identified a variant on 5q35 (rs60200309-A) near DOCK2 associated with severe COVID-19 in younger (<65 ages) patients (n=440, odds ratio=2.01, P=1.2×10). This risk allele was prevalent in East Asians but rare in Europeans, showing a value of non-European GWAS. RNA-seq of 473 bulk peripheral blood identified decreasing effect of the risk allele on DOCK2 expression in younger patients. DOCK2 expression was suppressed in severe forms of COVID-19. Single cell RNA-seq analysis (n=61) identified cell type-specific downregulation of DOCK2 and COVID-19-specific decreasing effects of the risk allele on DOCK2 in non-classical monocytes. Immunohistochemistry of lung specimens from severe COVID-19 pneumonia showed suppressed DOCK2. Moreover, inhibition of DOCK2 function using CPYPP induced much more severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection characterized as weight loss, lung edema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 plays an important role in the host immune response to SARS-CoV-2 infection and development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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http://dx.doi.org/10.1038/s41586-022-05163-5DOI Listing
August 2022

Syphilis in people living with HIV does not account for the syphilis resurgence in Japan.

J Infect Chemother 2022 Jul 31. Epub 2022 Jul 31.

Center for Promotion of Data Science, Juntendo University Graduate School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan; Department of Radiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.

Objectives: This study aimed to determine whether the current syphilis resurgence in Japan is attributable to incident syphilis in people living with HIV (PLWH).

Methods: This observational, retrospective, population-based study used data from the Japanese National Database. Data were extracted for PLWH who received antiretroviral treatment between January 2009 and December 2018. Using these data, along with the annual number of PLWH and syphilis diagnoses in the total population of Japan acquired from the National Institute of Infectious Diseases, the fraction of PLWH with syphilis compared to the total number of syphilis patients reported each year was calculated.

Results: There was a dramatic increase in syphilis cases during the study period. However, the incidence of syphilis in PLWH was stable during 2010-2018; the fraction of PLWH with newly diagnosed syphilis remaining at approximately 2% of the total PLWH cases in Japan each year. The proportion of newly diagnosed syphilis cases in PLWH decreased during the study period and accounted for <10% of the total syphilis cases in Japan since 2016 (14.9% in 2015 to 9.5% in 2016 and 5.9% in 2018). An increasing trend in the number of newly diagnosed syphilis cases in PLWH aged >50 years was observed (7.4% in 2010 to 10.4% in 2014 and 14.9% in 2018).

Conclusions: The recent dramatic increase in syphilis cases in Japan was not seen in PLWH. Thus, the resurgence of syphilis in Japan cannot be attributed to its transmission in the PLWH population.
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http://dx.doi.org/10.1016/j.jiac.2022.07.017DOI Listing
July 2022

Hypoprothrombinemia During Cefmetazole Treatment: A Case Report.

Am J Case Rep 2022 Jul 27;23:e936712. Epub 2022 Jul 27.

Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan.

BACKGROUND Cefmetazole (CMZ), containing an N-methyl-tetrazole-thiol (NMTT) side chain, is a therapeutic option for diverticulitis in Japan. Cephems containing an NMTT, a methyl-thiadiazol, and a thiadiazolethiol side chain are known to induce coagulation disorders. CASE REPORT A 76-year-old woman developed hypoprothrombinemia after receiving oral levofloxacin (LVFX) 250 mg q24h for 2 days followed by intravenous CMZ 2 g q8h for sigmoid diverticulitis. On day 5 of CMZ administration (after 12 doses in total), black stool was observed. On the following day (after 14 doses), prothrombin time (PT) prolongation was noted; PT and international normalized ratio (INR) were 37.1 s and 2.47, respectively. We diagnosed the patient with hypoprothrombinemia because of vitamin K deficiency caused by markedly elevated protein levels induced by vitamin K absence or antagonist-II on day 6 of CMZ administration. Intravenous vitamin K administration and CMZ cessation rapidly restored PT and led to the disappearance of black stool. CONCLUSIONS The causes of vitamin K deficiency were considered to be an impaired vitamin K cycle due to CMZ and decreased vitamin K intake because of malnutrition. These findings are consistent with CMZ's reported adverse effects. Decreased vitamin K production due to alterations in the gut bacterial flora by LVFX and CMZ was also postulated as a cause. If a bleeding tendency is noted during diverticulitis treatment with NMTT-containing cephems, switching to intravenous quinolones or carbapenems is recommended. It remains unclear how this reaction can be avoided; however, prudent monitoring of bleeding signs and PT-INR is recommended.
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http://dx.doi.org/10.12659/AJCR.936712DOI Listing
July 2022

Real-world medication persistence among HIV-1 patients initiating integrase inhibitor-based antiretroviral therapy in Japan.

J Infect Chemother 2022 Jul 16. Epub 2022 Jul 16.

Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan. Electronic address:

Introduction: Medication persistence has rarely been studied for integrase strand transfer inhibitor (INSTI)-based regimens among patients living HIV (PLWH) in Asia. This study investigated medication persistence for newly prescribed INSTI-based regimens in Japan by comparing single-tablet regimens (STRs) versus multiple-tablet regimens (MTRs), based on the Medical Data Vision database.

Methods: Adult PLWH with ≥2 claims for antiretroviral therapy (ART) of interest between 1 January 2017 and 30 June 2018 were included if they had a ≥3-month continuous enrolment prior to the index date and a ≥6-month follow-up after the index date. Medication persistence was measured as the duration from initiation to discontinuation of the prescribed INSTI-based regimen.

Results: Overall, 487 patients were included, with 220 in the STR cohort and 267 in the MTR cohort. Persistence was longer in the STR cohort than in the MTR cohort (mean days on the index regimens: 384.2 vs. 317.3, P < 0.001). MTRs were associated with a higher risk of discontinuation than STRs (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.18-2.52; P = 0.005). Other factors that were associated with discontinuation were backbone (emtricitabine/tenofovir disoproxil fumarate vs. emtricitabine/tenofovir alafenamide: HR, 5.64; 95% CI, 3.68-8.66; P < 0.001), third agent (raltegravir vs. elvitegravir/cobicistat: HR, 2.06; 95% CI, 1.10-3.86; P = 0.024), age (HR, 1.02; 95% CI, 1.01-1.03; P = 0.007), and the number of non-ART index medications (HR, 1.16; 95% CI, 1.12-1.21; P < 0.001).

Conclusions: Among PLWH newly prescribed an INSTI-based regimen in Japan, STRs were associated with longer persistence than MTRs.
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http://dx.doi.org/10.1016/j.jiac.2022.07.005DOI Listing
July 2022

Pneumomediastinum in a cheerleading student.

Clin Case Rep 2022 Jul 11;10(7):e6053. Epub 2022 Jul 11.

Department of General Medicine, Faculty of Medicine Juntendo University Tokyo Japan.

Spontaneous pneumomediastinum in healthy individuals is an uncommon entity. We are reporting an image of pneumomediastinum and subcutaneous emphysema in a male college student. The onset was considered to be the hard vocal exercise during his cheerleading club activity.
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http://dx.doi.org/10.1002/ccr3.6053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9272216PMC
July 2022

as a cause of uncontrollable colon bleeding.

IDCases 2022 20;29:e01547. Epub 2022 Jun 20.

Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.idcr.2022.e01547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253364PMC
June 2022

Reactogenicity and immunogenicity of BNT162b2 or mRNA-1273 COVID-19 booster vaccinations after two doses of BNT162b2 among healthcare workers in Japan: a prospective observational study.

Expert Rev Vaccines 2022 Jul 4:1-11. Epub 2022 Jul 4.

Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.

Background: This study evaluates the immunogenicity and reactogenicity of BNT162b2 and mRNA-1273 booster doses after the primary two-dose BNT162b2 series in Japan and is the first report from Western Pacific region.

Research Design And Methods: Healthcare workers receiving the two-dose BNT162b2 series and eligible for booster vaccination were enrolled. Self-reported adverse reactions were recorded for 8 days. Antibody titer was measured at baseline and on day 28.

Results: A total of 2,931 and 890 subjects received BNT162b2 (homologous) and mRNA-1273 (heterologous) booster vaccinations, respectively. The anti-SARS-CoV-2 spike protein IgG titer increased by 50.9- and 64.3-fold in the homologous and heterologous groups, respectively. Immunogenicity was greater with increasing age, regardless of sex. Adverse reactions were mild to moderate and decreased with age. The most common adverse reactions were injection-site pain (92.2%), fatigue (71.8%), headache (58.3%), and fever ≥37.5°C (46.5%). Two cases of non-severe myocarditis occurred in the heterologous group and resolved without clinical sequelae.

Conclusion: Homologous booster schedules had fewer reported adverse reactions; heterologous boosters elicited greater immunogenicity. Among different age groups, subjects aged 60 or over had the lowest immunogenicity before the booster, and both homologous and heterologous boosters restored vaccine immunogenicity level comparable to those of younger age groups.
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http://dx.doi.org/10.1080/14760584.2022.2093722DOI Listing
July 2022

Meals and Room Temperature Storage do not Significantly Affect Feasibility of Direct RT-PCR Tests for SARS-CoV-2 Using Saliva.

Clin Lab 2022 Jun;68(6)

Background: Rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using saliva samples has emerged as a preferred technique since sample collection is easy and noninvasive. In addition, several commercial high-throughput PCR kits that do not require RNA extraction/purification have been developed and are now available for testing saliva samples. However, an optimal protocol for SARS-CoV-2 RT-PCR testing of saliva samples using the RNA extraction/purification-free kits has not yet been established. The aim of this study was to establish optimal preanalytical conditions, including saliva sample collection, storage, and dilution for RNA extraction/purification-free RT-PCR (direct RT-PCR).

Methods: Patients suspected with COVID-19 from March 02 to August 31, 2020, were enrolled in this study. A total of 248 samples, including 43 nasopharyngeal swabs and 205 saliva samples, were collected from 66 patients (37 outpatients and 29 inpatients) and tested using the 2019 Novel Coronavirus Detection Kit (nCoV-DK, Shimadzu Corporation, Kyoto, Japan).

Results: The detection results obtained using nasopharyngeal swabs and saliva samples matched 100%. The sampling time, i.e., either awakening time or post-breakfast, had no significant effect on the viral load of the saliva samples. Although saliva samples are routinely diluted to reduce viscosity, we observed that dilution negatively affected PCR sensitivity. Saliva samples could be stored at room temperature (25°C) for 24 hours or at 4°C for up to 48 hours.

Conclusions: This study demonstrated the appropriate conditions of saliva sample collection, processing, and storage, and indicated that the nCoV-DK is applicable to saliva samples, making the diagnosis method simple and safe.
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http://dx.doi.org/10.7754/Clin.Lab.2021.210451DOI Listing
June 2022

A Case of Infective Endocarditis Associated With Patent Ductus Arteriosus in Which PET/CT Was Useful for Diagnosis.

Clin Nucl Med 2022 Sep 11;47(9):832-833. Epub 2022 Jun 11.

From the Departments of General Medicine.

Abstract: A 33-year-old woman presented to our hospital with a 4-month history of fever of unknown origin. Physical examination revealed a vascular murmur in the left subclavian region. Blood culture revealed bacteria and PET/CT revealed tracer accumulation in the patent ductus arteriosus area, leading to the diagnosis of infective endocarditis in this area. This case report may aid in diagnosing this disease in the future, as infective endocarditis in a patent ductus arteriosus is rare and difficult to diagnose.
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http://dx.doi.org/10.1097/RLU.0000000000004296DOI Listing
September 2022

Impact of a telemedicine system on work burden and mental health of healthcare providers working with COVID-19: a multicenter pre-post prospective study.

JAMIA Open 2022 Jul 20;5(2):ooac037. Epub 2022 May 20.

Department of Digital Health and Telemedicine R&D, Juntendo University, Tokyo, Japan.

Background: The coronavirus disease 2019 (COVID-19) pandemic impacts not only patients but also healthcare providers. This study seeks to investigate whether a telemedicine system reduces physical contact in addressing the COVID-19 pandemic and mitigates nurses' distress and depression.

Methods: Patients hospitalized with COVID-19 in 4 hospitals and 1 designated accommodation measured and uploaded their vital signs to secure cloud storage for remote monitoring. Additionally, a mat-type sensor placed under the bed monitored the patients' respiratory rates. Using the pre-post prospective design, visit counts and health care providers' mental health were assessed before and after the system was introduced.

Results: A total of 100 nurses participated in the study. We counted the daily visits for 48 and 69 patients with and without using the telemedicine system. The average patient visits were significantly less with the system (16.3 [5.5-20.3] vs 7.5 [4.5-17.5] times/day,  = .009). Specifically, the visit count for each vital sign assessment was about half with the telemedicine system (all  < .0001). Most nurses responded that the system was easy to use (87.1%), reduced work burden (75.2%), made them feel relieved (74.3%), and was effective in reducing the infection risk in hospitals (79.1%) and nursing accommodations (95.0%). Distress assessed by Impact of Event Scale-Revised and depression by Patient Health Questionnaire-9 were at their minimum even without the system and did not show any significant difference with the system ( = .72 and .57, respectively).

Conclusions: Telemedicine-based self-assessment of vital signs reduces nurses' physical contact with COVID-19 patients. Most nurses responded that the system is easy and effective in reducing healthcare providers' infection risk.
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http://dx.doi.org/10.1093/jamiaopen/ooac037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9129187PMC
July 2022

Antibody response and seroprevalence in healthcare workers after the BNT162b2 vaccination in a University Hospital at Tokyo.

Sci Rep 2022 05 24;12(1):8707. Epub 2022 May 24.

Department of Safety and Health Promotion, Juntendo University, Tokyo, Japan.

In 2020, we reported a low seroprevalence of N-specific antibodies in 4147 health care workers (HCWs) at a frontline hospital in Tokyo, Japan. In Japan, a vaccine campaign was launched in early 2021. We re-evaluated seroprevalences of N- and S-specific antibodies in 2202 HCWs who took two doses of the BNT162b2 vaccine. In 2021, N-specific seroprevalence remains as low as 1.59%. The seroprevalences were comparable among all HCWs regardless of exposure levels. Almost all of the HCWs elicited S-specific antibodies after vaccination. However, the HCWs who had COVID-19 elicited higher S-specific antibody titers than those who did not have COVID-19. In the HCWs without a history of COVID-19, 1.1% (23 out of 2185) were seropositive with N-specific antibodies, indicating the existence of asymptomatic infections. Also, S-specific antibody titers were higher in females and younger HCWs, and in those who had severe side effects. However, S-specific antibody titers were lower depending on the number of days after the second dose of vaccination specifically in elderly individuals. In conclusion, this study indicates N-specific seroprevalence remains low in HCWs at a frontline hospital in Tokyo. The mRNA vaccine elicited S-specific antibody in HCWs, however, the titers decreased as the days proceeded.
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http://dx.doi.org/10.1038/s41598-022-12809-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127282PMC
May 2022

Successful treatment with steroid pulse therapy for a COVID-19 case with progressive respiratory failure during treatment for pleural metastasis of breast cancer.

Surg Case Rep 2022 May 16;8(1):96. Epub 2022 May 16.

Department of General Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients are at high risk for developing severe conditions if other comorbidities are present, such as advanced cancer. Although the regulation of immune response is thought to play an important role in the treatment of coronavirus disease 2019 (COVID-19), physicians often have difficulties in selecting the most appropriate treatment. Furthermore, the impact that interrupting breast cancer treatment due to a COVID-19 infection has on patient outcomes is still unknown. Herein we report a case of advanced breast cancer in a patient whose COVID-19 acute respiratory failure was successfully treated with minimal interruption to their anticancer therapy for recurrent breast cancer.

Case Presentation: A 48-year-old woman developed carcinomatous pleurisy after curative surgery for breast cancer. One month after the initiation of targeted therapy with palbociclib and fulvestrant, the pleural effusion decreased, but soon after she developed a COVID-19 infection. Dexamethasone (8 mg/day) was administered due to a prolonged fever, but her respiratory symptoms got worse and pneumonia appeared on a computed tomography (CT) scan 7 days after hospitalization. Thus, steroid pulse therapy (methylprednisolone 1000 mg/day) was administered for 3 days. Her respiratory condition rapidly improved. Two weeks after hospital discharge, complete regression of pneumonia was confirmed on CT scan, and her targeted therapy was resumed at the same dose and strength. More than 6 months later, her metastatic disease remains stable while on the same treatment. Retrospective analysis of the patient's neutralizing antibodies found the neutralizing activity was low in the early stages of infection, but became high after recovery. This suggests the patient acquired an immunity to SARS-CoV-2 through the infection, despite having a mild myelosuppression due to treatment for recurrent breast cancer.

Conclusions: Steroid pulse therapy is available worldwide, and may have an important role in cancer patients who develop severe pneumonia from SARS-CoV-2, by enabling them to avoid any long-term disruption to anticancer therapy. Moreover, it might also be useful when antiviral therapies lose their efficacy due to mutations of the virus, such as the Omicron variant. A critical element in cases such as this one is that treatment decisions are made by a team of specialists, including pulmonologists.
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http://dx.doi.org/10.1186/s40792-022-01451-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108019PMC
May 2022

Increased delta variant SARS-CoV-2 infections in a highly vaccinated medical center in Japan.

Vaccine 2022 05 12;40(23):3103-3108. Epub 2022 Apr 12.

Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Japan.

The Delta variant has dominated SARS-CoV-2 infections in Tokyo, Japan from June 2021 to date. We conducted a retrospective cohort study to assess BNT162b2 vaccine effectiveness during the surge in Delta among 3,911 healthcare workers (HCWs) at a medical center of Tokyo with a high vaccination rate of 84.1%. With strict infection control protocols including universal masking, only a small number of cases among vaccinated and unvaccinated HCWs were identified before June. As Delta spread in Tokyo, 16 cases among 3,289 fully vaccinated HCWs and 11 cases among 574 unvaccinated HCWs were reported in July and August (case rate in August: 4.0 vs. 19.2 per 1,000). All breakthrough cases were confirmed as Delta. While our study confirms a robust vaccine effectiveness of BNT162b2 vaccine against Delta, rising breakthrough cases suggest that continued infection control measures are warranted in higher risk environments, even when high rates of vaccination coverage are achieved.
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http://dx.doi.org/10.1016/j.vaccine.2022.04.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001195PMC
May 2022

Psittacosis with a reversed halo sign.

Indian J Med Res 2021 04;154(4):650

Department of General Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.

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http://dx.doi.org/10.4103/ijmr.IJMR_1793_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204999PMC
April 2021

Uncommon presentation of Kikuchi disease.

Clin Case Rep 2022 Apr 4;10(4):e05673. Epub 2022 Apr 4.

Department of General Medicine Faculty of Medicine Juntendo University Tokyo Japan.

Kikuchi disease is common among Asians and women aged about 30 years. General symptoms include cervical lymphadenopathy and fever; 64% of the cases are self-limiting. However, this case is axillary lymphadenopathy, which is the main symptom in males. Thus, Kikuchi disease may be considered in the differential diagnosis of axillary lymphadenopathy.
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http://dx.doi.org/10.1002/ccr3.5673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979141PMC
April 2022

Pneumonia, influenza, and dengue cases decreased after the COVID-19 pandemic in Thailand.

Trop Med Health 2022 Mar 25;50(1):27. Epub 2022 Mar 25.

Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, 113-8431, Japan.

The coronavirus disease 2019 (COVID-19) pandemic has affected all healthcare systems worldwide. Effective COVID-19 preventive measures, including wearing a mask, hand washing, avoiding the "Three Cs", and city lockdowns, could decrease other infectious diseases. The case numbers of the major infectious diseases in Thailand were investigated (pneumonia, influenza, and dengue fever) during the COVID-19 pandemic using Thailand government national data sources from 2018 to August 2021. Pneumonia, influenza, and dengue fever cases decreased after the COVID-19 pandemic. In addition to respiratory tract infections, COVID-19 preventive measures could decrease dengue fever cases.
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http://dx.doi.org/10.1186/s41182-022-00419-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951655PMC
March 2022

A Case of Persistent Bacteremia Responding to a Combination of Vancomycin and Gentamicin.

Case Rep Infect Dis 2022 12;2022:8725102. Epub 2022 Mar 12.

Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.

A 56-year-old woman with a history of connective tissue disease developed fever, and () was detected in blood cultures. Therefore, treatment with vancomycin (VCM) was initiated. Since her blood cultures persistently detected despite peripheral intravenous catheter replacement and VCM treatment, concomitant treatment with gentamicin (GM) was started. Blood cultures then became negative. Persistent bacteremia responded to combination therapy with VCM and GM. This combination therapy may increase the risk of developing renal dysfunction, but the risk can be mitigated by appropriate therapeutic drug monitoring (TDM) and dose adjustments to achieve successful treatment.
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http://dx.doi.org/10.1155/2022/8725102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934234PMC
March 2022

What Causes Diagnostic Errors? Referred Patients and Our Own Cognitive Biases: A Case Report.

Am J Case Rep 2022 Mar 18;23:e935163. Epub 2022 Mar 18.

Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.

BACKGROUND We emphasize the utility of focusing on patient medical history and concerns rather than anchoring on data sent from referral institutions, which is often qualitative and devoid of useful patient-driven information. CASE REPORT A 21-year-old man was referred to our hospital with persistent back pain, hypoalbuminemia, and C-reactive protein (CRP) elevation after prolonged hospitalization for a UTI at another hospital. A review of systems (ROS) revealed chronic diarrhea and colonoscopy revealed Crohn's disease. Colonoscopy was followed by worsening back pain. Intestinal perforation was ruled out by X-ray, and analgesics were prescribed for long-standing scoliosis. The patient returned several days later with a recurrent UTI; a vesicointestinal fistula was identified, a known complication of Crohn's disease. This case involved diagnostic errors due to the doctors' faulty cognitive process. Also, in retrospect, we needed to be aware that the CT at the time of referral showed free air in the bladder and not uncomplicated pyelonephritis. The diagnostic errors were related to both satisfaction bias (finding one disease that prevents the accurate and timely diagnosis of another) and lack of awareness of epidemiology. To prevent errors like these, it is important to first conduct a careful interview and physical examination, as if the patient were a first-time patient, in order to eliminate the influence of bias. Next, epidemiological possibilities should be considered and differentiation made between physical and epidemiological issues. CONCLUSIONS It is important to treat referral patients as if they were first-time patients and to give due consideration to diagnostic biases and epidemiology.
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http://dx.doi.org/10.12659/AJCR.935163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938709PMC
March 2022

Relief Effect of Carbon Dioxide Insufflation in Transnasal Endoscopy for Health Checks-A Prospective, Double-Blind, Case-Control Trial.

J Clin Med 2022 Feb 24;11(5). Epub 2022 Feb 24.

Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan.

CO insufflation has proven effective in reducing patients' pain after colonoscopies but has not been examined in esophagogastroduodenoscopies. Therefore, we examined the effect of CO insufflation in examinees who underwent transnasal endoscopies without sedation. This study is a single-center, prospective, double-blind, case-control trial conducted between March 2017 and August 2018. Subjects were assigned weekly to receive insufflation with either CO or air. The primary outcome was improvement of abdominal pain and distension at 2 h and 1-day postprocedure. In total, 336 and 338 examinees were assigned to the CO and air groups, respectively. Visual analog scale (VAS) scores for abdominal distension (15.4 vs. 25.5; < 0.001) and distress from flatus (16.0 vs. 28.8; < 0.001) at 2 h postprocedure were significantly reduced in the CO group. VAS scores for pain during the procedure (33.5 vs. 37.1; = 0.059) and abdominal pain after the procedure (3.9 vs. 5.7; = 0.052) also tended to be lower at 2 h postprocedure, but all parameters showed no significant difference at 1-day postprocedure. All procedures were safely completed through the planned program, and no apparent adverse events requiring treatment or follow-up occurred. In conclusion, CO insufflation may reduce postprocedural abdominal discomfort from transnasal esophagogastroduodenoscopies. (UMIN000028543).
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http://dx.doi.org/10.3390/jcm11051231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911034PMC
February 2022

The 24-h reporting of Gram stains from positive blood cultures contributes to physician's use of appropriate antimicrobials: Experience at a university hospital.

J Infect Chemother 2022 Jun 3;28(6):836-839. Epub 2022 Mar 3.

Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address:

Although recent technological advances for the diagnosis of bloodstream infection (BSI) provide rapid and accurate results, blood culture maintains a key role in the diagnosis of BSI. The objective of this study was to determine whether 24-h reporting by telephone to disclose the suspected microorganism based on the Gram stain morphology from positive blood cultures (first laboratory report) affects a physician's use of appropriate antimicrobials. A total of 627 (14%) out of 4413 blood samples, excluding duplicate samples from the same patient on the same day, were positive for blood cultures between January and December 2016. The contamination rate of blood cultures during the study period was 2.3%. Among 627 patients with positive blood cultures, 538 (86%) were receiving antibiotics at the time of the first laboratory report, of which 502 (80%) thereafter continued the same antimicrobials, and the remaining 36 (6%) were changed to appropriate antimicrobials after the first laboratory report. An additional 25 (4%) were newly administered appropriate antimicrobials after the first laboratory report, whereas an additional 21 (3%) were newly administered appropriate antimicrobials after infection control team (ICT)-intervention. The median time lag (interquartile ranges) from flagging culture bottles as positive to a physician's use of appropriate antimicrobials after the first laboratory report (4 h, 2-7) was significantly (p < 0.001) shorter than that after ICT-intervention (12 h, 10-17). During the study period, no cases of discrepancy between the Gram stain morphology in the first laboratory report and definitive identification of microorganisms in the final laboratory report were observed. Because the timing of flagging culture bottles as positive tends to fall outside normal working hours, immediate 24-h reporting by telephone to disclose the suspected microorganism based on the Gram stain morphology from positive blood cultures may contribute to an early recognition of bacteremia and the physician's use of appropriate antimicrobials.
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http://dx.doi.org/10.1016/j.jiac.2021.12.035DOI Listing
June 2022

Comparison of the clinical parameters of patients with COVID-19 and influenza using blood test data: a retrospective cross-sectional survey.

J Int Med Res 2022 Feb;50(2):3000605221083751

Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.

Objective: The characteristic features, including blood test data, of the novel coronavirus disease 2019 (COVID-19) versus influenza have not been defined. We therefore compared the clinical parameters, including blood test data, of COVID-19 and influenza.

Methods: This retrospective cross-sectional survey was conducted at Juntendo University Nerima Hospital. We recruited patients diagnosed with COVID-19 between 1 January 2020 and 31 December 2020 who underwent blood tests. For comparison, we recruited an equivalent number of patients who were diagnosed with influenza and who underwent blood tests.

Results: During the study period, 228 patients (male:female, 123 [54.0%]:105 [46.0%]; age, 54.68 ± 18.98 years) were diagnosed with COVID-19. We also recruited 228 patients with influenza (male:female, 129 [56.6%]:99 [43.4%]; age, 69.6 ± 21.25 years). An age of 15 to 70 years (vs. 71 years), breathing difficulty, and malaise were significantly more common in patients with COVID-19 than in those with influenza. However, nausea, body temperature >38.1°C, and white blood cell count >9000/μL were more common in patients with influenza.

Conclusions: Our results are useful for differentiating COVID-19 from influenza, and these findings will be extremely helpful for future practice as we learn to coexist with COVID-19.
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http://dx.doi.org/10.1177/03000605221083751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894966PMC
February 2022

Basophilic stippling in red blood cells in the bone marrow: indication for lead poisoning diagnosis.

J Int Med Res 2022 Feb;50(2):3000605221078405

Department of General Medicine, Juntendo University Faculty of Medicine, Japan.

A 40-year-old man presented at our hospital with anaemia that had been undiagnosed for 2 years. Blood tests, endoscopy, and contrast-enhanced computed tomography were performed, but a definitive diagnosis could not be made. A subsequent bone marrow biopsy revealed basophilic stippling in transformed red blood cells, which led to a differential diagnosis of lead poisoning. Additional tests revealed elevated levels of lead in the blood. Basophilic stippling is generally found on a peripheral blood smear in lead poisoning patients; however, in this case, basophilic stippling was found only on the bone marrow smear and not in the blood smear. Even if basophilic stippling is not found in the peripheral blood, lead poisoning cannot be excluded.
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http://dx.doi.org/10.1177/03000605221078405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864261PMC
February 2022

as a cause of Löeffler's syndrome.

IDCases 2022 27;27:e01427. Epub 2022 Jan 27.

Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.

In 1936, Löeffler first recognized the association between a distinctive form of severe heart failure and marked eosinophilia. Most cases are caused by either parasitic infections or drugs; however, no cause has been identified in one-third of the patients [1]. This report presents a rare case of Löeffler's syndrome caused by the parasite Paragonimus westermani.
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http://dx.doi.org/10.1016/j.idcr.2022.e01427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808064PMC
January 2022

Large-Scale Observational Study on the Current Status and Challenges of General Medicine in Japan: Job Description and Required Skills.

Int J Gen Med 2022 29;15:975-984. Epub 2022 Jan 29.

Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.

Purpose: To identify the current ambiguous status of general medicine (GM) and assess current problems and weaknesses for further development of GM.

Patients And Methods: This study adopted an observational design. GM practitioners were selected from the mailing lists of two primary professional associations for Japanese GM doctors. We included physicians currently working in a GM department, those self-described as GM doctors, and those board-certified in family medicine or general internal medicine. Respondents replied to survey questions about their sociodemographic data, job descriptions, and the requisite skills for practice. GM doctors' job description and required skills were categorized into "clinical," "management," "education," and "research." Participants (n = 971) were compared based on job descriptions and important skills in each category by facility type, size, and position.

Results: "Clinical" was indicated as the most important category for both job description and important skills, followed by "management," "education," and "research." For job description details, "follow-up outpatient" (35.6%) ranked first for "clinical," and "resident education" (57.3%) ranked first for "education." By facility type and size, job description and important skills decreased for clinical and management categories as facility sizes increased; the opposite was true for "education." "Research" was generally rated low. By position, no significant difference was found in effort or importance given to research.

Conclusion: This study is the first survey on GM physicians across Japan. The results show that while Japanese GM physicians focus on and place importance on clinical practice, they are less involved in research and do not consider research skills to be important. The challenge for the future development of GM lies in research.
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http://dx.doi.org/10.2147/IJGM.S336828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811269PMC
January 2022

Decreased number of inpatients with community-acquired pneumonia during the COVID-19 pandemic: A large multicenter study in Japan.

J Infect Chemother 2022 May 21;28(5):709-713. Epub 2022 Jan 21.

Department of Public Health, Juntendo University Graduate School of Medicine, Japan.

The COVID-19 pandemic has shaped the dynamics of many diseases. This study aims to assess how the pandemic affected community-acquired pneumonia admission of all age groups among Japanese hospitals with various size and availability of COVID-19 wards. Our findings revealed a 44%-53% reduction in community-acquired pneumonia admission among 82 hospitals in Japan, from April through September of 2020, compared to the same period of 2019. Decreases were consistently found among hospitals with and without COVID-19 wards. The most significant decrease was found in the age group <20 years old. COVID-19 preventive measures and personal hygiene are considered to be effective measures to prevent the spreading of this disease. As vaccination progresses and the public gradually become less attentive to infection countermeasures, incidence of community-acquired pneumonia may increase in the coming season. Continued monitoring is required.
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http://dx.doi.org/10.1016/j.jiac.2022.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776425PMC
May 2022

Analysis of antiretroviral therapy switch rate and switching pattern for people living with HIV from a national database in Japan.

Sci Rep 2022 02 2;12(1):1732. Epub 2022 Feb 2.

Center for Promotion of Data Science, Juntendo University Graduate School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.

To report the status of switch rates and time-to-switch of antiretroviral therapy (ART) regimens by evaluating anchor drug classes and common switching patterns in Japanese people living with human immunodeficiency virus (HIV, PLWH). This cross-sectional cohort study extracted data of 28,089 PLWH from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), which contains data representing the entire population of Japan. PLWH with first prescription records of ART administered between January 2011 and March 2019 were identified (n = 16,069). The median time-to-switch and switch rates of anchor drug classes were estimated by Kaplan-Meier analysis. Brookmeyer-Crowley and Greenwood methods were used to estimate 95% confidence intervals for switch rates and median days, respectively. Switch rates were compared between anchor drug classes by year using log-rank tests. A total of 3108 (19.3%) PLWH switched anchor drug classes from first to second regimens. Switch rates increased continuously over 8 years for non-nucleoside reverse transcriptase inhibitors (NNRTIs) (14.9-65.5%) and protease inhibitors (PIs) (13.2-67.7%), with median time-to-switch of 1826 and 1583 days, respectively. Integrase strand transfer inhibitors (INSTIs) maintained a low switch rate (3.0-7.6%), precluding median-days calculation. Overall, the majority of patients treated initially with NNRTIs and PIs switched to INSTIs regardless of switching times (< 1 year: 67.3% and 85.9%, respectively; ≥ 1 year: 95.5% and 93.6%, respectively). The foremost switching strategies for first-to-second ART regimens are from NNRTIs or PIs to INSTIs regimens that maintain low switch rates long term. There was no observable difference in trend between sex, age and status of AIDS disease at first ART regimen. INSTIs HIV agents may be the most durable anchor drug class for PLWH receiving ART.
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http://dx.doi.org/10.1038/s41598-022-05816-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810755PMC
February 2022

Retrospective Study on the Effects of Glucose Abnormality on COVID-19 Outcomes in Japan.

Diabetes Ther 2022 Feb 30;13(2):325-339. Epub 2022 Jan 30.

Department of Metabolism and Endocrinology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan.

Introduction: To investigate the effects of glucose abnormality on outcomes of hospitalized coronavirus disease 2019 (COVID-19) patients in Japan.

Methods: This study retrospectively analyzed 393 COVID-19 patients admitted at Juntendo University Hospital. Patients were divided into subgroups according to history of diabetes and blood glucose (BG) levels and subsequently compared in terms of in-hospital death, invasive ventilation, or a composite of both.

Results: Patients with glucose abnormality demonstrated more risk factors for serious COVID-19, such as high body mass index, dyslipidemia, and hypertension, and higher biomarkers for inflammation compared to those with normal BG levels. Oxygen inhalation and steroid use were more frequent among patients with than without glucose abnormality. Invasive ventilation was more frequent in patients with diabetes (9.5% vs. 3.2%, p = 0.033) and BG ≥ 140 mg/dl (11.0% vs. 3.1%, p = 0.009) compared with those without diabetes and BG < 140 mg/dl, respectively. Logistic regression analysis showed that BG ≥ 140 mg/dl was a risk factor for invasive ventilation [odds ratio (OR) 2.87, 95% CI 1.04-7.68, p = 0.037] or the composite outcome (OR 3.03, 95% CI 1.21-7.38, p = 0.015) even after adjusting for by age and gender. Kaplan-Meier analysis showed that glucose abnormality was significantly associated with invasive ventilation and that BG ≥ 140 mg/dl was a risk factor for invasive ventilation [hazard ratio (HR) 2.68, 95% CI 1.05-6.82, p = 0.039] and the composite of death and invasive ventilation (HR 2.77, 95% CI 1.21-6.37, p = 0.016) regardless of age and gender.

Conclusions: Glucose abnormality, particularly BG ≥ 140 mg/dl, was associated with serious outcomes among Japanese COVID-19 patients, suggesting the need to consider high BG as a major risk factor for poor clinical course also in Japan.
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http://dx.doi.org/10.1007/s13300-022-01206-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801191PMC
February 2022

The universal relationship between sample dimensions and cooperative phenomena: effects of fractal dimension on the electronic properties of high- cuprate observed using electron spin resonance.

Phys Chem Chem Phys 2022 Feb 16;24(7):4147-4156. Epub 2022 Feb 16.

Graduate School of Science and Engineering, Ehime University, Matsuyama 790-8577, Japan.

As demonstrated by the unique electronic properties of nanostructured materials, which are qualitatively different from the bulk properties of the same materials, there should be a general relationship between the dimensions of the sample structures and the physical/chemical properties. However, it is demanding to examine this intriguing problem experimentally, because one cannot prepare a series of samples based on the same material with systematically varying and noninteger dimensions. This problem is solved by considering the fractal dimensions of samples. The electronic structures of a series of powder samples of the high- superconductor YBaCuO with the fractal dimensions () of 2.5-3.0 were investigated using the electron spin resonance (ESR) spectra at 293 K, to determine a general and quantitative relationship between the electronic properties and fractal dimensions of the samples. The observed -dependences of ESR parameters, such as -values and linewidths, were quantitatively consistent with those of the critical temperatures, critical current densities, and lower critical magnetic fields, all of which exhibited anomalies at ∼ 2.9. Considering the geometrical features of the fractal models, a hypothesis for explaining the observed -dependences of the cooperative phenomena has been proposed, suggesting a universal structural instability at particular fractal dimensions, which affects all the physical and chemical properties of the samples.
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http://dx.doi.org/10.1039/d1cp04709dDOI Listing
February 2022

Clinical prediction rule for bacteremia with pyelonephritis and hospitalization judgment: chi-square automatic interaction detector (CHAID) decision tree analysis model.

J Int Med Res 2022 Jan;50(1):3000605211065658

Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan.

Objective: This study was performed to identify predictive factors for bacteremia among patients with pyelonephritis using a chi-square automatic interaction detector (CHAID) decision tree analysis model.

Methods: This retrospective cross-sectional survey was performed at Juntendo University Nerima Hospital, Tokyo, Japan and included all patients with pyelonephritis from whom blood cultures were taken. At the time of blood culture sample collection, clinical information was extracted from the patients' medical charts, including vital signs, symptoms, laboratory data, and culture results. Factors potentially predictive of bacteremia among patients with pyelonephritis were analyzed using Student's -test or the chi-square test and the CHAID decision tree analysis model.

Results: In total, 198 patients (60 (30.3%) men, 138 (69.7%) women; mean age, 74.69 ± 15.27 years) were included in this study, of whom 92 (46.4%) had positive blood culture results. The CHAID decision tree analysis revealed that patients with a white blood cell count of >21,000/μL had a very high risk (89.5%) of developing bacteremia. Patients with a white blood cell count of ≤21,000/μL plus chills plus an aspartate aminotransferase concentration of >19 IU/L constituted the high-risk group (69.0%).

Conclusion: The present results are extremely useful for predicting the results of bacteremia among patients with pyelonephritis.
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http://dx.doi.org/10.1177/03000605211065658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743944PMC
January 2022

Efficacy and safety of semaglutide in glycemic control, body weight management, lipid profiles and other biomarkers among obese type 2 diabetes patients initiated or switched to semaglutide from other GLP-1 receptor agonists.

J Diabetes Metab Disord 2021 Dec 25;20(2):2121-2128. Epub 2021 Sep 25.

Department of General Medicine, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan.

Purpose: Evidence of the efficacy and safety of semaglutide among patients with type 2 diabetes who were initiated on or were switched to semaglutide from other GLP-1 RAs remains limited. The objective of this study was to investigate the short-term effects of switching to semaglutide from other GLP-1 RAs.

Methods: This retrospective cohort study evaluated patients with type 2 diabetes who were initiated on or were switched to semaglutide due to poor diabetes control with other GLP-1 RAs or other medications, or obesity. HbA1c, body weight, serum creatinine, serum uric acid, parameters of lipid metabolism, and parameters of liver function were measured before and 6 months after administration of semaglutide.

Results: A total of 50 patients were registered in the study. After switching to semaglutide (n = 43), HbA1c and body weight significantly decreased ( < 0.01,  < 0.01), respectively. The same findings were observed in semaglutide-naïve patients ( = 0.04,  < 0.02) (n = 7). Serum uric acid, total cholesterol, triglycerides, and urinary albumin-creatinine ratio decreased significantly as well ( = 0.04,  = 0.04,  = 0.02, p = 0.04), whereas serum creatinine did not change significantly ( = 0.51).

Conclusions: Semaglutide showed excellent efficacy, even in patients switched from other GLP-1 RAs. Semaglutide appears to be a promising agent for blood glucose and body weight control in obese type 2 diabetes mellitus patients and could be more potent in treating type 2 diabetes than existing GLP-1 RAs.
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http://dx.doi.org/10.1007/s40200-021-00899-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630305PMC
December 2021
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