Changes in the Hospital Standardized Mortality Ratio Before and During the COVID-19 Pandemic: A Disaggregated Analysis by Region and Hospital Type in Korea / 예방의학회지

Objectives@#The coronavirus disease 2019 (COVID-19) pandemic has led to a global shortage of medical resources; therefore, we investigated whether COVID-19 impacted the quality of non-COVID-19 hospital care in Korea by comparing hospital standardized mortality rates (HSMRs) before and during the pandemic. @*Methods@#This retrospective cohort study analyzed Korean National Health Insurance discharge claim data obtained from January to June in 2017, 2018, 2019, and 2020. Patients’ in-hospital deaths were classified according to the most responsible diagnosis categories. The HSMR is calculated as the ratio of expected deaths to actual deaths. The time trend in the overall HSMR was analyzed by region and hospital type. @*Results@#The final analysis included 2 252 824 patients. In 2020, the HSMR increased nationwide (HSMR, 99.3; 95% confidence interval [CI], 97.7 to 101.0) in comparison to 2019 (HSMR, 97.3; 95% CI, 95.8 to 98.8). In the COVID-19 pandemic zone, the HSMR increased significantly in 2020 (HSMR, 112.7; 95% CI, 107.0 to 118.7) compared to 2019 (HSMR, 101.7; 95% CI, 96.9 to 106.6). The HSMR in all general hospitals increased significantly in 2020 (HSMR, 106.4; 95% CI, 104.3 to 108.5) compared to 2019 (HSMR, 100.3; 95% CI, 98.4 to 102.2). Hospitals participating in the COVID-19 response had a lower HSMR (HSMR, 95.6; 95% CI, 93.9 to 97.4) than hospitals not participating in the COVID-19 response (HSMR, 124.3; 95% CI, 119.3 to 129.4). @*Conclusions@#This study suggests that the COVID-19 pandemic may have negatively impacted the quality of care in hospitals, especially general hospitals with relatively few beds. In light of the COVID-19 pandemic, it is necessary to prevent excessive workloads in hospitals and to properly employ and coordinate the workforce.

Effector Memory CD8 + and CD4 + T Cell Immunity Associated with Metabolic Syndrome in Obese Children / 대한소아소화기영양학회지

Purpose@#We investigated the association of effector memory (EM) CD8 + T cell and CD4 + T cell immunity with metabolic syndrome (MS). @*Methods@#Surface and intracellular staining of peripheral blood mononuclear cells was performed. Anti-interleukin-7 receptor-alpha (IL-7Rα) and CX3CR1 antibodies were used to stain the subsets of EM CD8 + T cells, while anti-interferon-gamma (IFN-γ), interleukin-17 (IL-17), and forkhead box P3 (FOXP3) antibodies were used for CD4 + T cell subsets. @*Results@#Of the 47 obese children, 11 were female. Children with MS had significantly higher levels of serum insulin (34.8±13.8 vs. 16.4±6.3 μU/mL, p<0.001) and homeostasis model assessment of insulin resistance (8.9±4.1 vs. 3.9±1.5, p<0.001) than children without MS.Children with MS revealed significantly higher frequencies of IL-7Rα low CD8+ T cells (60.1 ±19.1% vs. 48.4±11.5%, p=0.047) and IL-7Rα low CX3CR1 + CD8 + T cells (53.8±20.1% vs. 41.5 ±11.9%, p=0.036) than children without MS. As the serum triglyceride levels increased, the frequency of IL-7Rα low CX3CR1 + and IL-7Rα high CX3CR1 – CD8 + T cells increased and decreased, respectively (r=0.335, p=0.014 and r=−0.350, p=0.010, respectively), in 47 children. However, no CD4 + T cell subset parameters were significantly different between children with and without MS. @*Conclusion@#In obese children with MS, the changes in immunity due to changes in EM CD8 + T cells might be related to the morbidity of obesity.

Estimation of Excess All-cause Mortality during COVID-19 Pandemic in Korea

Background@#Excess all-cause mortality is helpful to assess the full extent of the health impact, including direct and indirect deaths of coronavirus disease 2019 (COVID-19). The study aimed to estimate overall and regional excess all-cause mortality during the pandemic in Korea. @*Methods@#We obtained all-cause death data and population statistics from January 2010 to December 2020. The expected mortality in 2020 was estimated using a quasi-Poisson regression model. The model included death year, seasonal variation, cold wave (January), average death counts in the previous month, and population. Excess mortality was defined as the difference between the observed mortality and the expected mortality. Regions were classified into three areas according to the numbers of COVID-19 cases. @*Results@#There was no annual excess all-cause mortality in 2020 at the national and regional level compared to the average death for the previous ten years. The observed mortality in 2020 was 582.9 per 100,000 people, and the expected mortality was 582.3 per 100,000 people (95% confidence interval, 568.3–596.7). However, we found monthly and regional variations depending on the waves of the COVID-19 pandemic in Korea. While the mortality in August, October, and November exceeded the expected range, the mortality in September was lower than the expected range. The months in which excess deaths were identified differed by region. @*Conclusion@#Our results show that the mortality in 2020 was similar to the historical trend.However, in the era of the COVID-19 pandemic, it would be necessary to regularly investigate COVID-19-related mortality and determine its direct and indirect causes.

Effector Memory CD8 + and CD4 + T Cell Immunity Associated with Metabolic Syndrome in Obese Children / 대한소아소화기영양학회지

Purpose@#We investigated the association of effector memory (EM) CD8 + T cell and CD4 + T cell immunity with metabolic syndrome (MS). @*Methods@#Surface and intracellular staining of peripheral blood mononuclear cells was performed. Anti-interleukin-7 receptor-alpha (IL-7Rα) and CX3CR1 antibodies were used to stain the subsets of EM CD8 + T cells, while anti-interferon-gamma (IFN-γ), interleukin-17 (IL-17), and forkhead box P3 (FOXP3) antibodies were used for CD4 + T cell subsets. @*Results@#Of the 47 obese children, 11 were female. Children with MS had significantly higher levels of serum insulin (34.8±13.8 vs. 16.4±6.3 μU/mL, p<0.001) and homeostasis model assessment of insulin resistance (8.9±4.1 vs. 3.9±1.5, p<0.001) than children without MS.Children with MS revealed significantly higher frequencies of IL-7Rα low CD8+ T cells (60.1 ±19.1% vs. 48.4±11.5%, p=0.047) and IL-7Rα low CX3CR1 + CD8 + T cells (53.8±20.1% vs. 41.5 ±11.9%, p=0.036) than children without MS. As the serum triglyceride levels increased, the frequency of IL-7Rα low CX3CR1 + and IL-7Rα high CX3CR1 – CD8 + T cells increased and decreased, respectively (r=0.335, p=0.014 and r=−0.350, p=0.010, respectively), in 47 children. However, no CD4 + T cell subset parameters were significantly different between children with and without MS. @*Conclusion@#In obese children with MS, the changes in immunity due to changes in EM CD8 + T cells might be related to the morbidity of obesity.

Estimation of Excess All-cause Mortality during COVID-19 Pandemic in Korea

Background@#Excess all-cause mortality is helpful to assess the full extent of the health impact, including direct and indirect deaths of coronavirus disease 2019 (COVID-19). The study aimed to estimate overall and regional excess all-cause mortality during the pandemic in Korea. @*Methods@#We obtained all-cause death data and population statistics from January 2010 to December 2020. The expected mortality in 2020 was estimated using a quasi-Poisson regression model. The model included death year, seasonal variation, cold wave (January), average death counts in the previous month, and population. Excess mortality was defined as the difference between the observed mortality and the expected mortality. Regions were classified into three areas according to the numbers of COVID-19 cases. @*Results@#There was no annual excess all-cause mortality in 2020 at the national and regional level compared to the average death for the previous ten years. The observed mortality in 2020 was 582.9 per 100,000 people, and the expected mortality was 582.3 per 100,000 people (95% confidence interval, 568.3–596.7). However, we found monthly and regional variations depending on the waves of the COVID-19 pandemic in Korea. While the mortality in August, October, and November exceeded the expected range, the mortality in September was lower than the expected range. The months in which excess deaths were identified differed by region. @*Conclusion@#Our results show that the mortality in 2020 was similar to the historical trend.However, in the era of the COVID-19 pandemic, it would be necessary to regularly investigate COVID-19-related mortality and determine its direct and indirect causes.

Loss of Heterozygosity at VHL, FHIT, and p16 Loci in Nonpapillary Renal Cell Carcinoma

The objectives of this study were to characterize the alterations of 3p and 9p in sporadic renal cell carcinomas (RCC) and to assess the relationship between the clinical stages or tumor size and the alteration of these chromosomes. Thirty eight archival, paraffin embedded tissue sections from 38 patients with RCC were analyzed for loss of heterozygosity (LOH) at 3p and 9p with 11 microsatellite markers. LOH was detected in 81.6% (31/38) and 37.8% (14/37) at 3p and 9p, respectively. The frequencies of LOH at VHL and FHIT locus were 75.6% and 72.2%, respectively. Twelve cases out of 38 showed LOH at both 9p21 and 3p. The loss of 3p in the samples tested was not related to clinical stages and tumor size, but that of 9p21 was significantly associated with advanced stage and larger tumor size. These results support that 3p deletion, including VHL and FHIT gene, play a critical role in the tumorigenesis of sporadic RCC, especially at early stage, and that 9p21 may contribute to the progression of sporadic RCC.

Identification of Zinc Finger Genes that are Differentially Expressed upon Apoptosis of Ramos B Cells

Typical programmed cell death requires de novo macromolecular synthesis and shares common morphological changes referred to as apoptosis. To elucidate the molecular mechanism of apoptosis, we isolated 13 cDNA clones of zinc finger genes that are differentially expressed in calcium ionophore-induced apoptosis of Ramos human B cell by 'targeted RNA fingerprinting' protocol (Stone & Wharton, 1993). According to DNA sequence analysis of the 13 cDNA clones, three clones are identical with ZNF7, ZNF143 and MTB-Zf, respectively, and 8 out of the other 10 clones showed partial homology to known zinc finger genes. Differential expression was confirmed in the three known zinc finger genes by ribonuclease protection assay. ZNF7 and ZNF143 are up-regulated after induction of apoptosis, and, in contrast, MTB-Zf is down-regulated. According to the previous reports on these three genes, all of the three genes have been suspected to be tumor suppressor genes, but their functions have not been identified yet. Taken together, our results suggest that many of the novel and known zinc finger genes might play important roles in regulation of apoptosis and that these findings also provide clues as to the functions of the three putative tumor suppressor genes, ZNF7, ZNF143 and MTB-Zf in terms of apoptosis. In addition, the isolation of zinc finger genes by targeted RNA fingerprinting could be a straightforward approach for the identification of novel candidate genes associated with apoptosis.

Identification of Differentially Expressed Genes Using RNA Fingerprinting in Cell after DNA Damage

RNA fingerprinting using on arbitrary primed polymerase chain reaction (RAP-PCR) was carried out to identify differentially expressed genes in HL-60 cell after treatment of methylmethane sulfonate (MMS). Twenty differentially expressed PCR products were cloned and analyzed. We have successfully obtained eight partial cDNA sequences by TA cloning method. Among these, six cDNAs were up-regulated and two cDNAs were down-regulated after the MMS treatment. Of these six up-regulated cDNAs, 3 cDNAs were equivalent to known genes in the GenBank/EMBL databases with 98~100% homology searched by BLAST program: genomic DNA fragment containing CpGg island (clone 26h8), Human Rev interacting protein-1 (RIP-1), and human zinc finger protein-4 (HZF4). The sequences of the three remaining cDNA were entirely new genes, but we didn't try to identify a full cDNA sequence. Two clones called KIAA0060 and KIAA0065, were down-regulated in HL-60 cells after the MMS treatment. These findings suggest that the RNA fingerprinting method using RAP-PCR is an effective method which can identify and separate the differentially expressed cDNAs and that the isolated cDNAs might involve in regulation mechanism of apoptosis and/or cell cycle delay, especially a p53-independent pathway, in the cells after DNA damage. But the nature of cDNAs that we have isolated remains to be elucidated.

The Role of gadd and p53 Genes in Apoptosis and Cell Cycle Delay by Genotoxic Agents

The aim of this study was to investigate the relationships between the gadd genes expression and an apoptosis induction in two different growing cell types after treatments with cisplatin and methylmethan sulfonate (MMS). We have examined the kinetics and specificity of gadd45 and gadd153 expression following cisplatin and MMS treatments to HL-60 cells and primary cultured human kidney (HKN) cells. We have also determined an induction time of apoptosis by DNA fragmentation analysis and the presence of the cell cycle arrest by a flow cytometric measurement. The results were as follows. In non-adherent HL-60 cells, a typical ladder pattern was observed within 4 hours after treatments of 20 micrometer of cisplatin and 100 microgram/ml of MMS. At the same time while adherent HKN cells failed to exhibit a ladder pattern at even higher doses of genotoxic agents. Since HL-60 cells do not have p53 gene, these findings suggest the presence of a p53-independent apoptotic pathway. The increasing patterns of the mRNA levels of gadd45 and gadd153 varied with the type of genotoxic agents. In the case of MMS treatment, the induction was rapid and transient, regardless of the cell types. The mRNA level peaked at 4 hours after MMS treatment and markedly decreased after 12 hours. On the other hand, cisplatin-induced transcriptions of gadd45 and gadd153 continued to increase for at least 24 hours and reached a peak level at 48 hours after cisplatin treatment, regardless of the cell types. HL-60 cells revealed G2 arrest following 24 hours after cisplatin and MMS treatments. These findings suggest that the regulation mechanism of apoptosis between adherent and non-adherent cells, might be different and that gadd45 and gadd153 might have an important role in DNA repair rather than apoptosis. Also, the findings suggest that an expression pattern of gadd45 and gadd153 might be different according to the type of genotoxic agents.