ABSTRACT
Background: Early detection of the illness trajectory in SARS-CoV-2 infected patients is crucial for patients and healthcare workers. A practical, non-invasive approach, with simple measurement for decision-making, is necessary for a pandemic to discriminate between high and low-risk patients, even though both may appear mild initially. Method(s): To determine COVID-19 disease severity within 10-days, distinguishing severe vs. moderate+mild and severe+moderate vs. mild, urinary L-type fatty acidbinding protein (L-FABP) was assayed less than four days after receiving a diagnosis. Severity was divided into mild (without oxygen), moderate (with oxygen) and severe (IMV/ECMO), and L-FABP within four days of diagnosis were used to predict severity within 10 days after onset. For risk prediction, urinary L-FABP was compared with interleukin-6. Next, the L-FABP point-of-care test (POCT) was further examined for its utility in risk screening in the international multicenter study. Result(s): Of the 224 participants in the study, 173 initially had a mild form. The AUC for a severe outcome was 96.3% in creatinine-adjusted L-FABP and 93.5% in net value. The AUC for a mild outcome was 85.0% and 84.9% net. The predictability of L-FABP for either a severe or mild outcome was superior to that of IL-6. Dynamics further showed better predictability of L-FABP than IL-6 during 10-days after onset. Finally, a multicenter-multicountry study confirmed the L-FABP POCT risk prediction of a severe outcome with an AUC of 88.9% and a mild outcome of 68.5%. Conclusion(s): Urinary L-FABP can predict the patient's risk of illness severity in COVID-19. L-FABP may detect severe cases more effectively and earlier than IL-6. L-FABP POCT is implementable for patient management.
ABSTRACT
Introduction: It is known that the number of patients with end-stage renal failure in ASEAN countries will certainly increase in the near future. However, many of these patients cannot receive good quality hemodialysis (HD) or any HD at all, resulting in death. The HD skill in Japan is top level expertise throughout the world. Therefore, the staff of the Department of Nephrology and Hemodialysis Unit of National Center for Global Health and Medicine (NCGM) have set forth to instruct the HD staff and physicians of some HD facilities, first in Malaysia, on our good technique and method of HD, in collaboration with Tsukuba International University and other HD-related companies of Japan. This project was a part of “Projects for global growth of medical technologies, systems and services through human resource development” funded by the Ministry of Health, Labour and Welfare. Methods: 1) The staff of the Department of Nephrology and HD Unit of NCGM with the collaborators visited HD facilities in Malaysia, surveyed their level and HD technique, and instructed the staff on our HD method and technique. 2) We invited the staff of the National Kidney Foundation of Malaysia (NKF) and other staff of HD facilities to visit Japan to inspect the HD method at NCGM, Tsukuba International University and a few other exemplary HD facilities in Tokyo. Further, we discussed the differences in HD method and technique between Japan and Malaysia. 3) We proposed that the system of clinical engineers (CE) working in HD facilities, which has been successfully established in Japan, should be established to improve the skill of HD in Malaysia. 4) We produced online videos on the sophisticated HD management and practice to show staff of HD facilities in Malaysia, as we could not directly instruct them due to the COVID-19 pandemic in the recent 2 years. Results: 1) We visited various HD facilities, small and large, in Malaysia 5 times in 2016, 2017 and 2018. We not only surveyed the level and technique of HD but also gave lectures on the Japanese method of HD. 2) We invited the primary staff of NKF as well as nurses and medical staff of the HD facilities, that we visited, to come to Japan. The staff who visited Japan directly observed and inspected the method and setting of HD at NCGM, Tsukuba International University and a few other HD facilities in Tokyo. The visitors could visualize and understand the Japanese method of HD in the clinical setting, and they had good discussion with the Japanese participants. 3) We proposed to the president of NKF and other experienced nephrologists in Malaysia that it is reasonable to establish the system of CE to develop high-level HD. We also presented the necessity of CE in Malaysia at the 34th Congress of the Malaysian Society of Nephrology, 2018. 4) We produced 2 sets of videos showing lessons on dialysis machines and electrical safety, and more than 40 Malaysian staff from HD facilities of a private clinic and a university hospital viewed them. Now we are newly preparing videos on other themes which can be viewed by more HD staff working in Malaysia on demand. Conclusions: We could successfully start the spread of higher-level HD in Malaysia. We are considering appropriate strategy to further improve the technical level of HD in Malaysia via online teaching methods. Conflict of interest Potential conflict of interest: This project was funded by the Ministry of Health, Labour and Welfare.
ABSTRACT
Background: The involvement of increased cytokine levels in severe COVID-19 has been noted, and anti-inflammatory therapy including corticosteroids or anti-human interleukin (IL)-6 receptor monoclonal antibody is expected to be effective in such patients. Direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX) is a treatment that selectively adsorbs endotoxins;it is also expected to adsorb a variety of endogenous substances. Methods: The patients (N=22) included were those whose respiratory samples tested positive for SARS-CoV-2 upon real-time reverse transcription-polymerase chain reaction (RT-PCR) and underwent PMX during hospitalization at National Center for Global Health and Medicine, Tokyo, Japan between January 30 2020 and April 30, 2021. PMX was considered when an image of pneumonia consistent with COVID-19 was obtained on chest CT and the P/F ratio was less than 300. Demographic data, information on clinical symptoms, and laboratory data were collected. Results: On day 15 of first PMX treatment, disease severity decreased in 63.6 % of the patients. P/F ratio increased and there was a downward trend in urine β2-microglobulin on days 4 and 8. Cytokine level measurement pre-and post-PMX revealed a downward trend in interleukin-6 levels and decreased levels of the factors involved in vascular endothelial injury, including vascular endothelial growth factor. There were 43 PMX, of which nine and five caused an increase in inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Conclusions: PMX is expected to become a therapy to address medical needs and prevent the exacerbation from moderate to severe condition in COVID-19.
ABSTRACT
Background: Early detection of coronavirus disease (COVID-19) in patients likely to develop severe manifestations enables appropriate interventions, including rapid intensive care unit admission. This study was conducted to determine whether noninvasive urine biomarkers can predict the clinical severity of COVID-19. Methods: Design A retrospective case series. Setting Single-center study, national center hospital designated for infectious disease. Patients Fifty-eight patients who tested positive for SARS-CoV-2 in respiratory specimens through real-time reverse transcription-polymerase chain reaction (RT-PCR) were retrospectively studied. Measurements and main results Urinary β2-microglobulin (β2MG), liver-type fatty acid-binding protein (L-FABP) were serially measured. Serum interferon γ and monocyte chemotactic protein-1 were also evaluated. Results: The 58 patients were assigned into three groups. Patients requiring intensive care were assigned to the severe group (N = 12). Patients treated with oxygen were assigned to the moderate group (N = 13). Other patients were assigned to the mild group (N = 33). Urine tests revealed that low β2MG and L-FABP levels on admission were associated with mild disease, whereas high levels were associated with severe disease. In severe cases, L-FABP tended to be persistently high. The resulting cutoff values were β2MG;Severe vs. Moderate+Mild: 2457 μg/dL (Specificity 76.9% and Sensitivity 90.0%, AUC 85.9%), L-FABP;Severe vs. Moderate+Mild: 22.0 μg/gCre (Specificity 84.6% and Sensitivity 90%, AUC 91.8%). Urinary β2MG and serum IFN-γ/MCP-1 showed a similar trend. Conclusions: Evaluating urinary biomarkers such as β2MG and L-FABP may allow determination of COVID-19 patients with active cytokines and recognition of patients likely to become critically ill and requiring careful observation and early intervention.