National Center For Global Health And Medicine Research Articles

The future of inbound medical care as gauged from the foreigners undergoing complete medical examinations in Japan.

Complete medical examinations are a system of preventive medicine unique to Japan. In recent years, Japanese and foreigners have been aware of complete medical examinations. However, the extent to which this concept of comprehensive medical checkup is recognized in different counties is unknown. The National Center for Global Health and Medicine (NCGM) is a facility that has been performing complete medical examinations on inbound visitors since May 2016, and more than 3,500 inbound visitors have been received to date. Based on this track record, the current study analyzed trends in foreigners' demand for medical checkups in Japan. From August 2020 to July 2023, 471 foreign residents in Japan from 22 countries were received. A certain proportion of examinees (approximately 30%) underwent examinations multiple times at a frequency of once a year. In addition, inbound medical visitors resumed starting in January 2023, and 158 inbound examinees were received. Of these, 15.2% of examinees had undergone a complete medical examination at the NCGM before the COVID-19 pandemic. This suggests that inbound medical visitors and foreign residents may regularly undergo complete medical examinations. In order to continue to meet this demand, Japanese medical facilities should enhance their system for receiving such examinees.

Urinary L-Type Fatty Acid-Binding Protein Predicts Oxygen Demand of COVID-19 in Initially Mild Cases.

To predict COVID-19 disease severity within 10 days, distinguishing cases that will progress to moderate or severe versus mild, patient urinary L-type fatty acid-binding protein (L-FABP) was assayed within 4 days of receiving a diagnosis. The study also examined whether L-FABP point of care (POC) test is helpful in risk screening. Symptomatic subjects who tested positive for SARS-CoV-2 and were hospitalized were prospectively enrolled at the National Center for Global Health and Medicine (NCGM), Yamanashi Prefectural Central Hospital (YPCH), and Sinai Hospital in Maryland. The outcome of each case was evaluated 7 days after admission and the diagnostic performance of L-FABP was assessed. Subjects were treated for COVID-19 at public healthcare centers in Japan from January 31, 2020, to January 31, 2021, to NCGM, YPCH, and at Sinai Hospital in Baltimore, MD, during the same period. The primary outcome was to determine whether urinary L-FABP within 48 hours of admission can predict the patient's severity of COVID-19 1 week later. We obtained demographic data, information on clinical symptoms, radiographic images, and laboratory data. Diagnostic performance was assessed using receiver operating characteristic analysis. Of the 224 participants in the study, 173 initially had a mild form of COVID-19. The area under the curve (AUC) for a severe outcome was 93.5%. L-FABP POC risk prediction of a severe outcome had an AUC of 88.9%. Urinary L-FABP can predict patient risk of COVID-19 illness severity. L-FABP POC is implementable for patient management. (ClinicalTrials.gov number, NCT04681040).

Infection control of COVID-19 in operating theaters in a designated hospital for specified infectious diseases in Japan.

At the beginning of the COVID-19 pandemic in 2020, many hospitals around the world recommended stopping elective surgery as a precaution to stop the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The number of elective surgeries was reduced in Japan due to several waves of the pandemic. This work describes the management of COVID-19 and actual polymerase chain reaction (PCR) screening in operating theaters at the National Center for Global Health and Medicine (NCGM), a designated hospital for specified infectious diseases in Japan. The following three steps for COVID-19 infection control were taken to maintain the operating theater: i) Do not bring COVID-19 into the operating theater, ii) Infection control for all medical staff, and iii) Surgical management of surgical patients with COVID-19. We introduced checklists for surgical patients, simulations of surgery on infected patients, screening PCR tests for all surgical patients, and use of a negative pressure room for infective or suspected cases. We determined the flow and timing of surgery for patients with COVID-19. However, many aspects of COVID-19 infection control measures in the operating theater are still unclear. Therefore, infection control measures require further advances in the future to manage new infections.

Cost-effectiveness of the prevention of parent-to-child transmission guidelines of HIV in India

BackgroundOne of the modes of transmission of HIV infection in India is from mother-to-child. In 2014, Prevention of Parent-to-child Transmission (PPTCT) guidelines of HIV in India were implemented which included shifting from Option A to Option B and B+. The aim of the present study was to evaluate health and cost related outcomes after implementation of these new guidelines. MethodsA decision analytical model was used to compare the PPTCT Option A with the new WHO Option of B and B+. Transmissions in serodiscordant couples and infants at 18 months were considered as health outcomes. The estimation of the cost for PPTCT services and HIV treatment was done using Costing Tool for Elimination Initiatives (CTEI) developed by National Center for Global Health and Medicine (NCGM). ResultsThe reduction in transmission rates in HIV infants was 33%. In serodiscordant couples the reduction in risk of HIV transmission from Option A to Option B and B+ was 72% and 87%, respectively. The incremental cost-effectiveness ratio (ICER) per quality adjusted life years (QALY) gained by averting infant infection, and for both infant and partner was US$ 238 and US$ 181 for Option B and US$ 1265 and US$ 947 for Option B+, respectively. ConclusionIt was found that Options B and B+ are more cost-effective as compared to option A. This effectiveness further increases when prevention of partner infections in Option B and B+ is taken into account.

Boosting multiregional clinical trials (MRCT) in Asia through the establishment of the Japan-led network for clinical research, the ARO alliance for ASEAN & East Asia (ARISE).

There is an increasing demand for clinical research, and this demand has particularly increased during the novel coronavirus infection (COVID-19) pandemic. In the light of these events, fostering international cooperation has become essential. The ARO Alliance for ASEAN & East Asia (ARISE) is a Japan-led international network for clinical research in Asia that was established to encourage and facilitate multiregional clinical trials. The Department of International Trials of the National Center for Global Health and Medicine (NCGM) launched ARISE in December 2021 to pursue efficacious, high-quality clinical research and ensure rapid responses to health emergencies, with the timely provision of new medicinal products to patients in Asia.

International technical cooperation to low- and middle-income countries during the COVID-19 pandemic.

This paper reports on the current status of international technical cooperation, reflecting the views of the Bureau of International Health Cooperation of the National Center for Global Health and Medicine (NCGM) during the COVID-19 pandemic. To appropriately respond to the pandemic, the need for assistance to low- and middle-income countries has increased. Since 2020, there has been a shift from on-site to online international technical cooperation to avoid human contact. While online solutions increased the number of participants in international conferences and training, business travel costs and time were reduced. However, it became necessary to consider not only effective labor-management practices to enable participation in meetings held in different time zones but also quicker ways to develop online training materials, which took a long time. In the future, a hybrid format combining offline and online international technical cooperation will become mainstream.

Infection prevention practices and its associated factors among hospital workers in a national medical center designated for COVID-19 in Tokyo, Japan.

BackgroundWhile healthcare workers (HCWs) are at risk of occupational exposure to SARS-CoV-2 infection, the virus transmission involving them might be exceeding in the non-occupational settings. This study examined the extent of adherence to infection prevention practices (IPPs) against COVID-19 in their daily life and its associated factors among staff members in a national medical center designated for COVID-19 treatment in Tokyo, Japan.MethodsThis cross-sectional study was conducted in July 2020 among 1,228 staff of National Center for Global Health and Medicine (NCGM). We asked participants about their adherence on six IPPs recommended by the WHO in their daily lives, which included wearing masks, maintaining hand and respiratory hygiene, avoiding 3Cs and social distancing. We defined 100% adherence (6 points) to IPPs as good adherence and run logistic regression model to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of IPPs.ResultsNearly 100% of NCGM staff members adhered to four out of six IPPs assessed in this study: washing or sanitizing hands (99.6%), good cough etiquette (99.6%), wearing mask (98.9%), and avoiding 3Cs (98.3%). Doctors (AOR = 2.18, CI: 1.36–3.49) and female staff members (AOR = 1.95, CI: 1.36–3.49) were more likely to adhere to IPPs compared with non-clinical staffs and male counterparts. Good adherence to IPPs tended to increase with older age, with highest adherence among those who were 50 years or above (AOR = 2.53, CI: 1.49–4.29).ConclusionThis study revealed that the IPPs among NCGM staff was remarkably good. Older and female staff members, and doctors showed a higher adhere to IPPs compared with their counterparts. Additional effort to improve adherence to IPPs among the younger and male staff members could contribute to reduce infection risk in their daily life, which can eventually prevent nosocomial infection.

An Association Study of HLA with the Kinetics of SARS-CoV-2 Spike Specific IgG Antibody Responses to BNT162b2 mRNA Vaccine.

BNT162b2, an mRNA-based SARS-CoV-2 vaccine (Pfizer-BioNTech, New York, NY, USA), is one of the most effective COVID-19 vaccines and has been approved by more than 130 countries worldwide. However, several studies have reported that the COVID-19 vaccine shows high interpersonal variability in terms of humoral and cellular responses, such as those with respect to SARS-CoV-2 spike protein immunoglobulin (Ig)G, IgA, IgM, neutralizing antibodies, and CD4+ and CD8+ T cells. The objective of this study is to investigate the kinetic changes in anti-SARS-CoV-2 spike IgG (IgG-S) profiles and adverse reactions and their associations with HLA profiles (HLA-A, -C, -B, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1) among 100 hospital workers from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. DQA1*03:03:01 (p = 0.017; Odd ratio (OR) 2.80, 95%confidence interval (CI) 1.05–7.25) was significantly associated with higher IgG-S production after two doses of BNT162b2, while DQB1*06:01:01:01 (p = 0.028, OR 0.27, 95%CI 0.05–0.94) was significantly associated with IgG-S declines after two doses of BNT162b2. No HLA alleles were significantly associated with either local symptoms or fever. However, C*12:02:02 (p = 0.058; OR 0.42, 95%CI 0.15–1.16), B*52:01:01 (p = 0.031; OR 0.38, 95%CI 0.14–1.03), DQA1*03:02:01 (p = 0.028; OR 0.39, 95%CI 0.15–1.00) and DPB1*02:01:02 (p = 0.024; OR 0.45, 95%CI 0.21–0.97) appeared significantly associated with protection against systemic symptoms after two doses of BNT162b2 vaccination. Further studies with larger sample sizes are clearly warranted to determine HLA allele associations with the production and long-term sustainability of IgG-S after COVID-19 vaccination.

A single-center descriptive study of untraced sources of infection among new cases of coronavirus disease in Tokyo, Japan.

We investigated possible sources of newly infected patients with coronavirus disease (COVID-19) after the fourth wave in order to explore unknown sources. Retrospective chart review on all the confirmed patients with COVID-19 admitted to the National Center for Global Health and Medicine (NCGM) in Tokyo, Japan was conducted from May 22 through June 29, 2021. Among the 22 participants, 14 (64%) had a history of known high-risk infection behaviors. Of those, 12 reported that their activities involved eating and drinking. In addition, there were 24 high-risk situations, of those, 21 (88%) were related to indoor dining, and masks were not worn in 22 situations (92%). New source of infection has not been identified. In situations with a high known risk of infection, many cases were related to eating and drinking, and insufficient use of masks was evident. Raising risk awareness on infection prevention and control of COVID-19 is urgently needed.

Smoking, Comorbidities, and Severity of Disease in Hospitalized COVID-19 Patients in Japan

Background: The aim of this study was to identify associations between smoking status and the severity of COVID-19 using a large-scale data registry of hospitalized COVID-19 patients in Japan (COVIREGI-JP) and to explore the reasons for the inconsistent results previously reported on this subject. Methods: The analysis included 17,702 COVID-19 inpatients aged 20-89 years (10,279 men and 7,423 women). We graded the severity of COVID-19 (grade 0 to 5) according to the most intensive treatment required during hospitalization. Associations of smoking status with severe grade 3/4/5 (invasive mechanical ventilation/extracorporeal membrane oxygenation/death) and separately with grade 5 (death) were analyzed using multiple logistic regression with grade 0 (no oxygen) as the control group. Results were expressed as odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and other factors considering the potential intermediate effects of comorbidities.Findings: Among men, former smoking significantly increased the risk of grade 3/4/5 and grade 5, with age-adjusted ORs (95% CI) of 1·50 (1·18-1·90) and 1·65 (1·23-2·21), respectively. An additional adjustment for comorbidities weakened these ORs to 1·29 (1·00-1·66) and 1.41 (1·01-1·95), respectively. Similar results were seen for women. Current smoking did not significantly increase the risk of grade 3/4/5 and grade 5 in either sex.Interpretation: Smoking cessation should be recommended even if the observed relationship between current smoking and the severity of COVID-19 is null because current smoking increases the risks of future comorbidities due to different diseases that increase the risk of severe COVID-19.Funding Information: This research was funded by the Health and Labour Sciences Research grant (19HA1003, 20CA2031) and the National Center for Global Health and Medicine (20A-3002).Declaration of Interests: All authors report no conflict of interest.Ethics Approval Statement: This study was approved by the National Center for Global Health and Medicine (NCGM) ethics review (NCGM-G-003494-0).

Japanese WHO Collaborating Centres (WHO CCs) fight against COVID-19.

WHO Regional Office for the Western Pacific (WPRO) organized an online meeting connecting WHO Collaborating Centres (WHO CCs) in the region on 25 August 2020, to share experiences and promote networking on COVID-19 response. The meeting shared regional update on situation and responses, and COVID-19 related experiences of selected WHO CCs, followed by discussions on opportunities for enhancing collaboration between WPRO and WHO CCs. Priorities of WPROs support to countries included a health systems approach rather than single intervention. On behalf of WHO CCs in Japan, the National Center for Global Health and Medicine (NCGM) delivered a presentation on the results of a survey about COVID-19 related activities of these WHO CCs. These activities were categorized into collaboration with WHO, research and development, public health responses, and clinical services. Collaboration with WHO included sending consultants through the scheme of GOARN, strengthening of COVID-19 testing, and contribution to development of WPRO guidelines. Research and development involved establishment of a nationwide registry of COVID-19 clinical data. Following the meeting, NCGM further enhanced its activities as WHO CC. Since WHO CCs in the country have a wide range of expertise that could contribute to health system strengthening, it is worthwhile for the WHO CCs to consider amending existing work plans for supporting countries in the region to incorporate a health systems approach as part of COVID-19 response strategies.

HLA-A*11:01:01:01, HLA-C*12:02:02:01-HLA-B*52:01:02:02, Age and Sex Are Associated With Severity of Japanese COVID-19 With Respiratory Failure.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19) was announced as an outbreak by the World Health Organization (WHO) in January 2020 and as a pandemic in March 2020. The majority of infected individuals have experienced no or only mild symptoms, ranging from fully asymptomatic cases to mild pneumonic disease. However, a minority of infected individuals develop severe respiratory symptoms. The objective of this study was to identify susceptible HLA alleles and clinical markers that can be used in risk prediction model for the early identification of severe COVID-19 among hospitalized COVID-19 patients. A total of 137 patients with mild COVID-19 (mCOVID-19) and 53 patients with severe COVID-19 (sCOVID-19) were recruited from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan for the period of February–August 2020. High-resolution sequencing-based typing for eight HLA genes was performed using next-generation sequencing. In the HLA association studies, HLA-A*11:01:01:01 [Pc = 0.013, OR = 2.26 (1.27–3.91)] and HLA-C*12:02:02:01-HLA-B*52:01:01:02 [Pc = 0.020, OR = 2.25 (1.24–3.92)] were found to be significantly associated with the severity of COVID-19. After multivariate analysis controlling for other confounding factors and comorbidities, HLA-A*11:01:01:01 [P = 3.34E-03, OR = 3.41 (1.50–7.73)], age at diagnosis [P = 1.29E-02, OR = 1.04 (1.01–1.07)] and sex at birth [P = 8.88E-03, OR = 2.92 (1.31–6.54)] remained significant. The area under the curve of the risk prediction model utilizing HLA-A*11:01:01:01, age at diagnosis, and sex at birth was 0.772, with sensitivity of 0.715 and specificity of 0.717. To the best of our knowledge, this is the first article that describes associations of HLA alleles with COVID-19 at the 4-field (highest) resolution level. Early identification of potential sCOVID-19 could help clinicians prioritize medical utility and significantly decrease mortality from COVID-19.

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

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

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 (n = 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%] vs. 9/745 [1.2%]: p = 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.

Nursing care for patients with COVID-19 on extracorporeal membrane oxygenation (ECMO) support.

In Japan, four medical facilities including our own - the National Center for Global health and Medicine (NCGM) - have been designated for the treatment of specified infectious diseases by the Minister of Health, Labour, and Welfare. Here, we report our nursing care for patients with severe COVID-19 on extracorporeal membrane oxygenation (ECMO) support. In addition to infection control measures in the form of an N95 mask, a water-repellent isolation gown, a cap, a shielded mask on top of the N95, and double-layered gloves, nurses were required to wear one-piece suits (DuPont™ Tyvek®) and use powered air-purifying respirators (PAPRs). While closed system catheters are normally changed once a day to limit aerosol exposure, they are now changed once every 4 days. Nursing care included equipment checks, monitoring of hemodynamics and respiratory status, management of anticoagulants, observation of the patients general condition, management of sedatives and analgesics, prevention of medical device-related pressure ulcers and bedsores, and maintenance of hygiene. Fundamentally sound nursing remains the best practice for patient treatment and management. During nursing care for patients with COVID-19 on ECMO, infection control measures should be faithfully and properly followed.

International technical transfer of training systems and skills in emergency medicine and trauma management: experiences of the National Center for Global Health and Medicine, Japan.

For over 20 years, the National Center for Global Health and Medicine (NCGM), Japan has been involved in international assistance for emergency medicine and trauma management in many countries, including Bolivia, Vietnam, Laos, Cambodia, and Mongolia. Among the NCGM activities conducted, the most important is technical assistance for the appropriate transfer of training systems and skills in life support management. In most of the target countries, the development and execution of customized simulation training suitable for each setting has successfully motivated trainees, who are healthcare workers responsible for improving emergency medical services in their home country. Moreover, the development of appropriate training systems for trainers selected from among capable participants has played a key role in the subsequent sustained conducting of training courses independent of NCGM involvement.

High prevalence and incidence of rectal Chlamydiainfection among men who have sex with men in Japan.

BackgroundRectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections have been neglected and epidemiological data are unavailable in Japan. Thus, we evaluated the prevalence and incidence of rectal CT/NG in a cohort of HIV-negative men who have sex with men (MSM), which was established at the National Center for Global Health and Medicine (NCGM), in Tokyo, Japan, in January 2017.MethodsHIV-negative MSM aged ≥16 years old were included. The prevalence of rectal CT/NG among HIV-negative MSM was compared with that among an existing HIV-positive MSM cohort at NCGM. The HIV-negative MSM cohort was examined for rectal and pharyngeal CT/NG every 3 months. Urethral CT/NG was evaluated at the physician’s discretion. The incidences of CT/NG were evaluated in December 2018.ResultsOf 502 MSM initially included in this study, 13 men were diagnosed with HIV infection at enrollment and were subsequently excluded from the analysis. We evaluated 561 HIV-positive MSM for rectal CT/NG. The mean ages of the two cohorts were 33.6 and 46.2 years old, respectively (p<0.001). The prevalences of rectal CT were 16.4% and 15.9% (p = 0.707) and the prevalences of rectal NG were 4.1% and 2.3% (p = 0.101), for the HIV-negative and HIV-positive MSM cohorts, respectively. Of 489 HIV-negative MSM, 328 were followed at least twice, with 261.1 person-years during the study period. The incidences of rectal CT/NG were 17.2 and 3.8/100 person-years and the incidences of pharyngeal CT/NG were 2.0 and 11.0/100 person-years for the two cohorts, respectively. Approximately 37.9% of incident cases were attributed to recurrent infection.ConclusionsThe prevalence and incidence of rectal CT/NG were high among MSM in Tokyo, Japan, suggesting that urgent countermeasures for early diagnosis and treatment are necessary.

Efficient and practical dissemination of information on viral hepatitis in Japan: an effort by the Hepatitis Information Center, National Center for Global Health and Medicine.

One of the important missions of the Hepatitis Information Center is to disseminate information regarding liver disease. The Hepatitis Information Center, National Center for Global Health and Medicine (NCGM) has been endeavoring to ensure that reliable and up-to-date information on liver disease is accessible to all people, regardless of age, disability, and background. Described here are several initiatives with regard to the dissemination of information about liver disease including: i) Education tool for youth, ii) Conversion of materials on liver diseases into audio format for the visually impaired, and iii) Hepatic Disease Medical Navigation System (Hepatic Navi). Hepatic Navi is a web-based search tool that informs users of the location and other information concerning medical centers where people can be tested for the hepatitis virus for free or at reduced cost. Hepatic Navi consolidates data from 47 prefectures into one database. The system depicts data via an interface that can be accessed anywhere with a PC, tablet, smart phone, or mobile phone. As a result, it has become possible for anyone from anywhere to access information on hepatitis virus testing. By using Hepatic Navi, it is anticipated that general people in need feel free to access to the testing and further treatment for virus hepatitis.

A Retrospective Single-center Analysis of 16 Cases of Imported Chikungunya Fever in Japan.

Objective Chikungunya fever (CHIK) is a re-emerging arboviral disease that is transmitted through the bite of infected Aedes mosquitoes. There is limited information regarding the epidemiology and clinical information of imported CHIK in Japan. The objective of this study was to review the epidemiology and clinical information of imported CHIK patients treated at the National Center for Global Health and Medicine (NCGM). Methods We evaluated all patients (n=16) who were diagnosed with imported CHIK and treated at the NCGM between October 1, 2005 and March 31, 2016. Results The primary complaint of 7 patients who presented to the NCGM after 31 days from disease onset was persistent arthritis, and the primary complaints of 9 patients who presented within 30 days after disease onset were a fever, headache, arthralgia, and rash. Eleven patients experienced a rash during the first week of illness. The median duration of the arthralgia was 75 days, and the joint pain lasted for >2 months in 8 patients and >6 months in 3 patients. Persistent arthralgia was not significantly associated with an age of >35 years (p=0.13) or patient sex (p=0.69). All 16 patients exhibited positive results for CHIK IgM, although only 4 exhibited positive real-time polymerase chain reaction results. Conclusion Physicians should consider CHIK in patients with a fever who have returned from areas where CHIK is endemic.

Correlation Between Prognosis and Morphological Abnormalities in Multiple Myeloma

BackgroundMultiple myeloma shows various morphological abnormalities such as plasmablastic morphology, cytoplasmic granules, vacuolation, and nuclear atypia. Although plasablastic morphology has been revealed as a poor prognostic factor, little is known about clinical significance of other abnormalities. Therefore we investigated a correlation between morphological abnormalities and clinical outcome.MethodsPatient SelectionA total of 76 multiple myeloma patients who hospitalized in National Center for Global Health and Medicine (NCGM), Japan, between 2010 and 2015 were enrolled in this study.Morphological EvaluationBone marrow smears were obtained from each patient before initiation of treatments. We evaluated Greipp's morphological classification and morphological abnormalities of myeloma cells including cytoplasmic granules, vacuolation, and nuclear atypia. We also evaluated morphological abnormalities of other hemocytes. All specimens were observed at 400x magnification with an optical microscope.Clinical InformationClinical information obtained from medical records of NCGM includes gender, age, overall survival, Durie-Salmon staging system (DS), international staging system (ISS), types of M protein and light chain. The results of G-banded chromosomal analysis and fluorescent in situ hybridization (FISH) analysis were also collected from medical records.Statistical AnalysisWe performed survival analysis by generalized Wilcoxon test with EZR (version 1.31).ResultsClinical DataOf all the patients, 46 (60.5%) are male. Mean age of the patients is 63.5 years old.Morphological Abnormality of Myeloma CellsAccording to Greipp's morphological classification, we identified 13 cases as mature type (17.1%), 28 cases as intermediate type (36.8%), 31 cases as immature type (40.8%), 4 cases as plasmablastic type (5.3%). We found cytoplasmic granules in 20 cases (26.3%), vacuolation in 8 cases (10.5%), atypical myeloma cells in 54 cases (71.1%), Russell bodies in 5 cases (6.6%), and Dutcher bodies in 3 cases (3.9%).Morphological Abnormality of Other HematocytesAs for myeloid cells, we found Auer rods in 1 case (1.3%), pseudo-Pelger-Huet anomaly in 2 cases (2.6%), neutrophils with ring-shaped nuclei in 2 cases (2.6%), megakaryocytes with multiple separated nuculeus in 3 cases (3.9%).Statistical AnalysisWe revealed that overall survival of granular group is significantly longer than non-granular group (p=0.04, Fig.1). Median overall survivals are 66.2 months (granular group) vs 54.5 months (non-granular group). However, there are no significance of vacuolation and nuclear atypia on overall survival.ConclusionsA variety of morphological abnormalities were identified in multiple myeloma. We found that presence of cytoplasmic granules in myeloma cells correlates with good prognosis.DiscussionPrevious reports have shown that cytoplasmic granules of myeloma cells contain immunoglobulin however pathophysiological roles of them remain unclear. Further studies with molecular and cellular analysis should be carried out to elucidate roles of cytoplasmic granules. [Display omitted] DisclosuresHagiwara:Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.