In light of the recent pandemic, favipiravir (Avigan^®), a purine nucleic acid analog and antiviral agent approved for use in influenza in Japan, is being studied for the treatment of coronavirus disease 2019 (COVID-19). Increase in blood uric acid level is a frequent side effect of favipiravir. Here, we discussed the mechanism of blood uric acid elevation during favipiravir treatment. Favipiravir is metabolized to an inactive metabolite M1 by aldehyde oxidase and xanthine oxidase, and excreted into urine. In the kidney, uric acid handling is regulated by the balance of reabsorption and tubular secretion in the proximal tubules. Favipiravir and M1 act as moderate inhibitors of organic anion transporter 1 and 3 (OAT1 and OAT3), which are involved in uric acid excretion in the kidney. In addition, M1 enhances uric acid reuptake via urate transporter 1 (URAT1) in the renal proximal tubules. Thus, favipiravir is thought to decrease uric acid excretion into urine, resulting in elevation of uric acid levels in blood. Elevated uric acid levels were returned to normal after discontinuation of favipiravir, and favipiravir is not used for long periods of time for the treatment of viral infection. Thus, the effect on blood uric acid levels was subclinical in most studies. Nevertheless, the adverse effect of favipiravir might be clinically important in patients with a history of gout, hyperuricemia, kidney function impairment (in which blood concentration of M1 increases), and where there is concomitant use of other drugs affecting blood uric acid elevation.

The number of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly increased, although the WHO declared a pandemic. However, drugs that function against SARS-CoV-2 have not been established. SARS-CoV-2 has been suggested to bind angiotensin-converting enzyme 2, the receptor of the SARS coronavirus. SARS coronavirus and coronavirus 229E, the cause of the common cold, replicate through cell-surface and endosomal pathways using a protease, the type II transmembrane protease. To examine the effects of protease inhibitors on the replication of coronavirus 229E, we pretreated primary cultures of human nasal epithelial (HNE) cells with camostat or nafamostat, each of which has been used for the treatment of pancreatitis and/or disseminated intravascular coagulation. HNE cells were then infected with coronavirus 229E, and viral titers in the airway surface liquid of the cells were examined. Pretreatment with camostat (0.1-10 μg/mL) or nafamostat (0.01-1 μg/mL) reduced the titers of coronavirus 229E. Furthermore, a significant amount of type II transmembrane protease protein was detected in the airway surface liquid of HNE cells. Additionally, interferons have been reported to have antiviral effects against SARS coronavirus. The additive effects of interferons on the inhibitory effects of other candidate drugs to treat SARS-CoV-2 infection, such as lopinavir, ritonavir and favipiravir, have also been studied. These findings suggest that protease inhibitors of this type may inhibit coronavirus 229E replication in human airway epithelial cells at clinical concentrations. Protease inhibitors, interferons or the combination of these drugs may become candidate drugs to inhibit the replication of SARS-CoV-2.

In thyroid pathology, the great variety of types and the wide range of aggressiveness of thyroid cancers complicate both diagnosis and management. In 2016, a subset of noninvasive encapsulated follicular variant of papillary thyroid carcinoma was reclassified as noninvasive follicular thyroid tumor with papillary-like nuclear features (NIFTP) to reduce overtreatment of this low-risk tumor that follows a benign course after surgery. Starting from a paradigmatic clinical case, in this short review, we will summarize the ultrasonography, cytological, histological and molecular features of this new entity. In the preoperative settings, the recognition of some peculiar elements may only suggest the possibility of a NIFTP, thus favoring a less aggressive surgical approach. However, the diagnosis of NIFTP can only be made after complete resection of the lesion by detecting well-defined inclusion and exclusion histopathological criteria. Since NIFTP is not ‘malignant,’ surgery may be considered curative with no further treatment or surveillance needed. NIFTP-related issues, including nodule size, multifocality, oncocytic changes, heterogeneous incidence across different geographical areas and its occurrence in the pediatric age, will be discussed.

The double burden of malnutrition is the coexistence of two different conditions, mainly reflected as excess or deficit in weight. Anemia is a specific nutritional deficit not always included in the double burden assessment. We reviewed overweight and/or obesity (OW/OB) and anemia studies from Latin-American Children over the last ten years up to 2019. Two authors evaluated the MEDLINE, SCOPUS, and LILACS databases. A scale of ten questions was used to assess the risk of bias in prevalence studies. Fourteen studies were selected. The population studies’ size ranged from 147 to 20,342 children with different socio-economic backgrounds, such as urban, peri-urban and rural settings, socio-economic status, schooling, population (ethnic minorities and indigenous), and environmental differences (sea level or high altitude). The prevalence of OW/OB ranged from 4.9% to 42%. The prevalence of anemia was from 3.4% to 67%. The double burden, including OW/OB and anemia, ranged from 0.7% to 67%. A higher prevalence of excess weight and anemia was found in rural and high altitude above sea level environments, extreme poverty, low education level, and indigenous communities. These heterogeneous data, before the 2020 (COVID-19 pandemic), reflect the vast inequities between countries and within each country. Food insecurity linked to poverty and the induced change in eating habits and lifestyles threaten optimal child nutrition in ongoing and future scenarios. The existence of OW/OB and anemia and their simultaneous coexistence in the community, home, and individual levels, indicates that interventions should be comprehensive to face the double burden of malnutrition.

During a disaster, all hospitals are expected to function as “social critical institutions” that protect the lives and health of people. In recent disasters, numerous hospitals were damaged, and this hampered the recovery of the affected communities. Had these hospitals business continuity plans (BCPs) to recover quickly after the disaster, most of the damage could have been avoided. This study conducted a scoping review of the historical trend and regional differences in hospital BCPs to validate the improvement of the BCP concept based on our own experience at Tohoku University Hospital, which was affected by the 2011 Great East Japan Earthquake and Tsunami (GEJET). We searched PubMed by using keywords related to BCP and adapted 97 articles for our analysis. The number of articles on hospital BCPs has increased in the 2000s, especially after Hurricane Katrina in 2005. While there are regional specificity of hazards, there were many common topics and visions for BCP implementation, education, and drills. From our 2011 GEJET experience, we found that BCPs assuming region-specific disasters are applicable in various types of disasters. Thus, we suggest the following integral and universal components for hospital BCPs: (1) alternative methods and resources, (2) priority of operation, and (3) resource management. Even if the type and extent of disasters vary, the development of BCPs and business continuity management strategies that utilize the abovementioned integral components can help a hospital survive disasters in the future.

The Tohoku Medical Megabank biobank (TMM biobank) is the first major population-based biobank established in Japan. The TMM biobank was established based on two population cohorts and is a reconstruction program from the Great East Japan Earthquake and Tsunami of 2011. The biobank stores more than 3.4 million tubes of biospecimens and associated health and analytic data obtained from approximately 150,000 TMM cohort participants between May 2013 and December 2018, and the TMM biobank currently shares high-quality specimens and data. Various biospecimens, including peripheral and cord blood mononuclear cells, buffy coat, plasma, serum, urine, breast milk and saliva have been collected in the TMM biobank. To minimize human error and maintain the quality of data and specimens, we have been utilizing laboratory information management system into various biobank procedures from registration to storage with various automation systems, such as liquid dispensing, DNA extraction and their storage. The biobank procedures for the quality management system (ISO 9001:2015) and information security management system (ISO 27001:2013) are certified by the International Organization for Standardization. The quality of our biobank samples fulfills the pre-analytical requirements for researchers conducting next-generation whole genome sequencing, DNA array analyses, proteomics, metabolomics, etc. We established analytical centers to conduct standard genomic and multiomic analyses in-house and share the generated data. Additionally, we generate thousands of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and proliferating T cells for functional studies. The TMM biobank serves as an indispensable infrastructure for academic, clinical and industrial research to actualize next-generation medicine in Japan.

Chronic pancreatitis (CP) is a pancreatic disease with poor prognosis characterized clinically by abdominal pain, morphologically by pancreatic stones/calcification, duct dilatation and atrophy, and functionally by pancreatic exocrine and endocrine insufficiency. CP is also known as a risk factor for the development of pancreatic cancer. CP has long been understood based on a fixed disease concept deduced from the clinical and morphological features of the end-stage disease. However, identification of causal genes for hereditary pancreatitis and success in the isolation and culture of pancreatic stellate cells have advanced the understanding of the underlying pathological mechanisms, the early-stage pathophysiology, and the mechanisms behind pancreatic fibrosis. These advances have led to moves aimed at improving patient prognosis through prevention of disease progression by early diagnosis and early therapeutic intervention. The strategy for preventing disease progression has included a proposal for diagnostic criteria for early CP and introduction of a new definition of CP in consideration of the pathological mechanisms. Our group has been committed deeply to these studies and has provided a large amount of information to the world.

Modern day health care providers have traditionally only focused on meeting the response phase requirements of disasters. The emergence of complex global public health crises such as climate change and extremes, biodiversity loss, emergencies of scarcity, rapid unsustainable urbanization, migrant and refugee surges, domestic and international terrorism, cyber-security, the civilianization of war and conflict, and the global rise of resistant antibiotics has resulted in an unprecedented rise in direct and indirect mortality and morbidity. These crises are beyond the current decision-making and operational capabilities of traditional disaster management and its providers most of who are community level practitioners representing every discipline. The 1930s “disaster cycle” concept describes a phase-related approach to meeting the strategic, operational, research, educational, and training components required of disasters; and, presents an opportunity for the structured development of a Health Crisis Management Framework to oversee the phase-related strategic and operational requirements for prevention, preparedness, response, recovery and rehabilitation challenges of major global public health crises. Whereas this approach mimics the manner in which practitioners at every level of society identify with in their daily practices, this approach deserves the support of every clinician, researcher, academic, and ancillary health care provider. Interestingly, this was also the intent of the original 1930 disaster cycle concept.