Analysis of Cause-of-Death Mortality in Children and Young Adults with Diabetes: A Nationwide 10-Year Follow-Up Cohort Study.

We examined the associations of clinical characteristics and cause-of-death patterns with mortality in children and young adults (<30 years) with diabetes. We analyzed a nationwide cohort sample from the KNHIS database using propensity score matching from a sample of 1 million people from 2002 to 2013. There were 10,006 individuals in the diabetes mellitus (DM) group and 10,006 in the control (no DM) group. The numbers of deaths were 77 in the DM group and 20 in the control group. The deaths of patients in the DM Group were 3.74 (95% confidence interval (CI) = 2.25-6.21) times higher than in the control group. Type 1 DM, type 2 DM and unspecified DM were 4.52 (95% CI = 1.89-10.82) times, 3.25 (95% CI = 1.95-5.43) times and 10.20 (95% CI = 5.24-20.18) times higher, respectively. Mental disorders were 2.08 times higher in the risk of death (95% CI = 1.27-3.40). Mortality rates have increased in children and young adults with diabetes alone. Therefore, in the future, it is necessary to identify the cause of the increased mortality rate among young diabetic people and select vulnerable groups among them so that early prevention can be achieved.

Development of an External Control Arm Using Electronic Health Record-Based Real-World Data to Evaluate the Efficacy of COVID-19 Treatment.

To protect people from severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, tremendous research efforts have been made toward coronavirus disease 19 (COVID-19) treatment development. Externally controlled trials (ECTs) may help reduce their development time. To evaluate whether ECT using real-world data (RWD) of patients with COVID-19 is feasible enough to be used for regulatory decision making, we built an external control arm (ECA) based on RWD as a control arm of a previously conducted randomized controlled trial (RCT), and compared it to the control arm of the RCT. The electronic health record (EHR)-based COVID-19 cohort dataset was used as RWD, and three Adaptive COVID-19 Treatment Trial (ACTT) datasets were used as RCTs. Among the RWD datasets, eligible patients were evaluated as a pool of external control subjects of the ACTT-1, ACTT-2, and ACTT-3 trials, respectively. The ECAs were built using propensity score matching, and the balance of age, sex, and baseline clinical status ordinal scale as covariates between the treatment arms of Asian patients in each ACTT and the pools of external control subjects was assessed before and after 1:1 matching. There was no statistically significant difference in time to recovery between ECAs and the control arms of each ACTT. Among the covariates, the baseline status ordinal score had the greatest influence on the building of ECA. This study demonstrates that ECA based on EHR data of COVID-19 patients could sufficiently replace the control arm of an RCT, and it is expected to help develop new treatments faster in emergency situations, such as the COVID-19 pandemic.

Regulating the microenvironment with nanomaterials: Potential strategies to ameliorate COVID-19.

COVID-19, caused by SARS-CoV-2, has resulted in serious economic and health burdens. Current treatments remain inadequate to extinguish the epidemic, and efficient therapeutic approaches for COVID-19 are urgently being sought. Interestingly, accumulating evidence suggests that microenvironmental disorder plays an important role in the progression of COVID-19 in patients. In addition, recent advances in nanomaterial technologies provide promising opportunities for alleviating the altered homeostasis induced by a viral infection, providing new insight into COVID-19 treatment. Most literature reviews focus only on certain aspects of microenvironment alterations and fail to provide a comprehensive overview of the changes in homeostasis in COVID-19 patients. To fill this gap, this review systematically discusses alterations of homeostasis in COVID-19 patients and potential mechanisms. Next, advances in nanotechnology-based strategies for promoting homeostasis restoration are summarized. Finally, we discuss the challenges and prospects of using nanomaterials for COVID-19 management. This review provides a new strategy and insights into treating COVID-19 and other diseases associated with microenvironment disorders.

Influenza viral infection is a risk factor for severe illness in COVID-19 patients: a nationwide population-based cohort study.

In order to prepare for the twindemic of influenza and SARS-CoV-2 infection, we investigated the association between influenza infection and subsequent severity of SARS-CoV-2 infection. A population-based nationwide cohort study was performed using data from the National Health Insurance Service (NHIS) in the Republic of Korea. This study included 274,126 individuals who underwent SARS-CoV-2 PCR testing between 20 January 2020 and 1 October 2020. Among these patients, 28,338 tested positive for SARS-CoV-2, and 4,003 of these individuals had a history of influenza. The control group was selected through 1:1 propensity score matching. In the group of 4,003 COVID-19-positive individuals with no history of influenza, 192 (4.8%) experienced severe illness from COVID-19 infection. In the group of 4,003 COVID-19-positive individuals with a history of influenza, 260 (6.5%) had severe illness from COVID-19, and the overall adjusted odds ratio (aOR) was 1.29 (95% confidence interval 1.04-1.59). Among the 4,003 COVID-19-positive individuals with a history of influenza, severe COVID-19 infection was experienced by 143 of 1,760 (8.1%) with an influenza history within 1 year before the onset of COVID-19, 48 of 1,129 (4.3%) between 1 and 2 years, and 69 of 1,114 (6.2%) between 2 and 3 years before COVID-19 onset, and the aORs were 1.54 (1.20-1.98), 1.19 (0.84-1.70), and 1.00 (0.73-1.37), respectively. In conclusion, individuals who had an influenza infection less than 1 year before COVID-19 infection were at an increased risk of experiencing severe illness from the SARS-CoV-2 infection. To control the public health burden, it is essential that effective public health control measures, which include influenza vaccination, hand washing, cough etiquette, and mask use are in place.

Metal-based anticancer agents as immunogenic cell death inducers: the past, present, and future.

Cancer is the deadliest disease in the world behind heart disease. Sadly, this remains true even as we suffer the ravages of the Covid-19 pandemic. Whilst current chemo- and radiotherapeutic treatment strategies have significantly improved the patient survival rate, disease reoccurrence continues to pose a deadly risk for all too many patients. Incomplete removal of tumour cells from the body increases the chances of metastasis and developing resistance against current treatments. Immunotherapy represents a therapeutic modality that has helped to overcome these limitations in recent decades. However, further progress is needed. So-called immunogenic cell death (ICD) is a recently discovered and unique mode of cell death that could trigger this necessary further progress. ICD involves stimulation of a tumour-specific immune response as a downstream effect. Facilitated by certain treatment modalities, cells undergoing ICD can trigger the IFN-γ mediated immune response involving cytotoxic T cells (CTLs) and γδ T cells that eradicate residual tumour cells. In recent years, there has been a significant increase in the number of small-molecules being tested as potential ICD inducers. A large number of these ICD inducers are metal-based complexes. In fact, anticancer metal drugs based on Pt, Ru, Ir, Cu, and Au are now known to give rise to an immune response against tumour cells as the result of ICD. Advances have also been made in terms of exploiting combinatorial and delivery strategies. In favourable cases, these approaches have been shown to increase the efficacy of otherwise ICD "silent" metal complexes. Taken in concert, rationally designed novel anticancer metal complexes that can act as ICD inducers show promise as potential new immunotherapies for neoplastic disease. This Tutorial Review will allow the readers to assess the progress in this fast-evolving field thus setting the stage for future advances.

COPD is a risk factor for COVID-19, but does not confer increased severity of the disease.

Epidemiologic studies suggest that COPD is associated with an increased risk of poor outcome in patients with COVID-19, although they failed to demonstrate COPD as a risk factor for acquiring COVID-19. However, most data have come from a limited global population. In this nationwide cohort study based on the Korean national health insurance claims-based database, COPD is associated with increased risk for COVID-19 and having COPD does not seem to confer substantial risk for severe COVID-19 and mortality. These findings indicate that heterogeneity in the populations across many countries may complicate the net effects of COPD on the COVID-19-related outcomes.

A materials-science perspective on tackling COVID-19.

The ongoing SARS-CoV-2 pandemic highlights the importance of materials science in providing tools and technologies for antiviral research and treatment development. In this Review, we discuss previous efforts in materials science in developing imaging systems and microfluidic devices for the in-depth and real-time investigation of viral structures and transmission, as well as material platforms for the detection of viruses and the delivery of antiviral drugs and vaccines. We highlight the contribution of materials science to the manufacturing of personal protective equipment and to the design of simple, accurate and low-cost virus-detection devices. We then investigate future possibilities of materials science in antiviral research and treatment development, examining the role of materials in antiviral-drug design, including the importance of synthetic material platforms for organoids and organs-on-a-chip, in drug delivery and vaccination, and for the production of medical equipment. Materials-science-based technologies not only contribute to the ongoing SARS-CoV-2 research efforts but can also provide platforms and tools for the understanding, protection, detection and treatment of future viral diseases.