Relationship of severity of hyponatremia and adverse outcomes in children visiting the emergency department.

Mild hyponatremia is often found in patients visiting pediatric emergency departments (PEDs), but there are few large-scale studies on its association with adverse outcomes, including mortality. We conducted this study to identify the association of mild hyponatremia with adverse outcome. This retrospective observational study included children under 18 years of age visiting the PED at a tertiary hospital. We used electronic medical record data from January 1, 2009 to December 31, 2020. Clinical outcomes, including ward admission, vasopressor administration, pediatric intensive care unit (PICU) admission, and mortality, were assessed for the total of 44,147 patients. Among these, 1,639 (3.7%) were in the hyponatremia group, with 1,521 (3.4%) exhibiting mild hyponatremia. Mild hyponatremia was more prevalent in younger patients, particularly in the 1-3 years age group, and less common in females. Patients with mild hyponatremia had a significantly prolonged median length of stay in the PED compared to normonatremic patients (5.8 h vs. 4.4 h, p < 0.001). Moreover, they showed significantly higher rates of ward admission (51.1% vs. 35.6%, p < 0.001), vasopressor administration (1.1% vs. 0.6%, p = 0.014), PICU admission (2.4% vs. 1.0%, p < 0.001), and mortality (1.5% vs. 0.3%, p < 0.001). Compared with the normonatremia group, the odds ratios (95% CI) for ward admission, vasopressor administration, PICU admission, and mortality in the mild hyponatremia group were 1.90 (1.71-2.10), 1.91 (1.17-3.13), 2.62 (1.86-3.68), and 5.56 (3.51-8.80), respectively. Furthermore, our findings demonstrate a notable upward trend in adverse outcomes, including vasopressor administration, PICU admission, and mortality, from mild hyponatremia to severe hyponatremia. In conclusion, we found that adverse outcomes increase with the severity of hyponatremia in children presenting to the PED, highlighting the importance of immediate intervention alongside the identification of the underlying cause.

Risk of Developing Hypertension in Atopic Dermatitis Patients Receiving Long-term and Low-dose Cyclosporine: A Nationwide Population-based Cohort Study.

BACKGROUND: Cyclosporine (CS) is a first-line immunosuppressive agent used to manage moderate to severe atopic dermatitis (AD). To date, the risk of developing hypertension associated with the long-term use of low-dose CS in AD patients is understudied. OBJECTIVE: To determine the cumulative dose-dependent effect of CS on the risk of developing hypertension in patients with AD. METHODS: A nationwide population-based retrospective cohort with 1,844,009 AD patients was built from the Korean National Health Insurance System database from 2005 to 2009. A Cox proportional-hazard regression analysis was performed according to patients' CS treatment history adjusted for potential confounders. RESULTS: Current use of CS was associated with an increased risk of developing hypertension (adjusted hazard ratio, 4.442; 95% confidence interval, 3.761-5.247). Among the current CS users, a higher cumulative dose of CS (≥39,725 mg) or longer cumulative use of CS (≥182 days), was significantly associated with an increased risk of developing hypertension. CONCLUSION: The incidence of CS-associated hypertension is very low when using low-dose treatment regimens for AD. However, the current use or a high cumulative dose of CS for treating patients with AD increases the risk of developing hypertension. Precaution is needed when prescribing CS for long-term treatment of AD.

Incidence of invasive fungal diseases in inflammatory bowel disease patients: A nationwide study in South Korea.

BACKGROUND: Limited reports exist regarding invasive fungal diseases (IFDs) in inflammatory bowel disease (IBD) patients. OBJECTIVES: This study aims to investigate the incidence and risk factors of IFDs, specifically invasive candidiasis, aspergillosis and pneumocystosis, in IBD patients in South Korea using nationwide data. PATIENTS/METHODS: A population-based retrospective cohort of 42,913 IBD patients between January 2010 and December 2018 was evaluated using the Health Insurance Review and Assessment database. The primary outcome was the incidence of IFDs, including invasive candidiasis, aspergillosis and pneumocystosis, while the secondary outcome involved analysing the risk factors associated with each specific infection. RESULTS: The study included a total of 42,913 IBD patients, with 29,909 (69.7%) diagnosed with ulcerative colitis (UC) and 13,004 (30.3%) diagnosed with Crohn's disease (CD). IFDs occurred in 166 IBD patients (0.4%), with 93 cases in UC patients and 73 cases in CD patients. The incidence rates of invasive candidiasis, aspergillosis and pneumocystosis in IBD patients were 0.71 per 1000 person-years (PYs), 0.15 per 1000 PYs and 0.12 per 1000 PYs, respectively. The cumulative incidence of invasive candidiasis (adjusted p-value <.001) and Pneumocystosis (adjusted p-value = .012) was found to be higher in CD patients than in UC patients. Each IFD had different risk factors, including IBD subtypes, age at diagnosis, anti-tumour necrotic factor agents or the Charlson comorbidity index. CONCLUSION: Based on nationwide data in South Korea, this study shows that IFDs occur consistently in patients with IBD, albeit with a low frequency.

Estimation of Supply and Demand for Cardiologists in Korea.

BACKGROUND AND OBJECTIVES: The objective of this study was to estimate the supply and demand for cardiologists in Korea and provide evidence for healthcare policy to ensure a stable and adequate workforce for optimal cardiovascular disease management. METHODS: Past trends of inflow and outflow of cardiologists were used to make crude projections, which were then adjusted based on demands of services to obtain final projections. Inflow of cardiologists was estimated using second-order polynomial regression and demand for cardiology care was estimated using linear regression. RESULTS: There were 1,139 active cardiologists who were under the age of 65 in clinical practice in Korea. The estimated number of cardiologists from 2022 to 2040 showed that the number of cardiologists would peak at 1,344 in 2032 and gradually decrease thereafter. We also estimated an increase of 947,811 cases of heart-related procedures annually from 2023 to 2032. The number of heart-related procedures per cardiologist would increase 1.4 times from 12,964 in 2023 to 17,862 in 2032. The estimated number of emergency patients per cardiologist under 50 years old would almost double from 544 in 2022 to 987 in 2032. CONCLUSIONS: We expect significant shortage of cardiologists in Korea within the next 10 years. The number of emergency patients per cardiologist will increase by nearly 50%, leading to high individual workload for cardiologists. To prevent this imbalance between supply and demand, an organized and collective approach by the specialty of cardiology is imperative to produce a balanced workforce.

Long-term effects of adenotonsillectomy in children with attention deficit hyperactivity disorder.

STUDY OBJECTIVES: Adenotonsillectomy (AT) improves short-term symptoms of attention deficit hyperactivity disorder (ADHD) in children; however, its long-term effects remain unclear. We aimed to verify the therapeutic long-term effects of AT in children with ADHD. METHODS: This retrospective control study included children ages < 18 years who were diagnosed with ADHD and receiving ADHD medications. Participants were divided into groups depending on whether AT was performed (AT [+] or AT [-] groups) and matched 1:1 for age, sex, and year and month of diagnosis using randomized nonreplacement selection. RESULTS: Among patients with ADHD (n = 171,112), 3,615 underwent AT. In both groups, the number of drugs taken gradually increased before and decreased after the AT date (ATD). There was no difference in the number of drugs used before (P = .88) and after ATD (P = .06). Before ATD, the average number of outpatient visits (nOV) did not change in both groups (AT [+]: P = .12; AT [-]: P = .71). After ATD, the average number of outpatient visits decreased only in the AT (+) group (P = .001). However, there was no difference in the average number of outpatient visits between the two groups before (P = .47) and after ATD (P = .17). Before ATD, methylphenidate doses between the groups were not different (P = .06); however, a significant increase was noted after ATD in the AT (+) group (P < .001). CONCLUSIONS: AT does not result in significant long-term therapeutic effects in terms of medication use and health care utilization in children with ADHD. CITATION: Lee J, Choi A, Kim S, Kim K. Long-term effects of adenotonsillectomy in children with attention deficit hyperactivity disorder. J Clin Sleep Med. 2024;20(5):727-733.

The Prevalence and Risk Factors of Clostridioides difficile Infection in Inflammatory Bowel Disease: 10-Year South Korean Experience Based on the National Database.

BACKGROUND: Few studies evaluate the epidemiology and risk factors of Clostridioides difficile infection (CDI) in Asian patients with inflammatory bowel disease (IBD). We investigated the year-end prevalence, cumulative incidence and risk factors of CDI in Asian patients with IBD using a large-scale population-based cohort in Korea. METHODS: Using the National Health Insurance Service database, we identified patients with IBD and sex- and age-matched controls without IBD between 2008 and 2018. The year-end prevalence and cumulative incidence of CDI were compared among patients with Crohn's disease (CD) and ulcerative colitis (UC) with controls. The risk factors for CDI were evaluated. RESULTS: Among the 54,836 patients with IBD and 109,178 controls, CDI occurred in 293 patients with IBD and 87 controls. The annual year-end prevalence of CDI in patients with IBD increased from 8.6/10,000 persons in 2008 to 22.3/10,000 persons in 2018. The risk of CDI was higher in both patients with CD and UC than that in the matched controls (hazard ratio [HR], 7.285; 95% confidence interval [CI], 5.388-9.851; P < 0.001 and HR, 7.487; 95% CI, 5.796-9.670; P < 0.001, respectively). Among patients with IBD, the risk factors for CDI included older age, female sex, high Charlson comorbidity index score, and IBD-related medications including oral 5-aminosalicylic acid, immunomodulatory agents, biologics, and steroids used for > 90 days. CONCLUSION: The risk of CDI in Korean patients with IBD was approximately seven times higher than that in controls without IBD, and the annual year-end prevalence of CDI continuously increased from 2008 to 2018.

Usage trends of colorectal endoscopic submucosal dissection according to hospital types based on nationwide claims data.

Although the use of colorectal endoscopic submucosal dissection (ESD) for colorectal lesions has increased, there is a lack of analysis of the recent usage trends of ESD. Thus, this study aimed to identify changes in the annual utilization of ESD and determine the proportion of surgeries after ESD according to hospital types. Using Health Insurance Review and Assessment data from 2012 to 2019, 26,502 colorectal ESD cases were analyzed to assess the annual usage trends of ESD according to hospital type, additional early and late surgeries after ESD, changes in the distribution of colorectal lesions, and factors associated with early and late surgery. Trend analysis was performed using the chi-squared test for trend in proportions. Colorectal ESD increased from 2046 in 2012 to 5319 in 2019. Additional early and late surgeries rose from 135 (6.6%) in 2012 to 441 (8.2%) in 2019 (P < .05) and from 9 (0.3%) in 2013 to 52 (1.0%) in 2019 (P < .05), respectively. In tertiary and general hospitals, the proportion of submucosal cancers decreased, whereas the proportion of intramucosal cancers increased. Submucosal cancer was associated with early (odds ratio: 108.90, 95% confidence interval: 61.67-192.35) and late surgery (odds ratio: 3.55, 95% confidence interval: 2.27-5.56). Using nationwide data, our study identified the clinical usage trends of colorectal ESD based on the annual increase in utilization and the proportion of additional surgeries after ESD.

Risk Factors for the Occurrence and Severity of Vertebral Fractures in Inflammatory Bowel Disease Patients: A Nationwide Population-Based Cohort Study.

BACKGROUND: The risk of vertebral fractures is increased in inflammatory bowel disease (IBD) patients. However, whether the severity of vertebral fractures differs between IBD patients and the general population, or between patients with Crohn's disease (CD) and ulcerative colitis (UC), is unknown. METHODS: We investigated risk factors associated with the occurrence and severity of vertebral fractures in IBD patients using The National Healthcare Insurance Service (NHIS) database. We defined the patients who underwent vertebroplasty or kyphoplasty after being diagnosed with a vertebral fracture as having a severe vertebral fracture than those with only diagnosis codes. RESULTS: From 2008 to 2018, there were 33,778 patients with IBD (24,370 UC patients and 9,408 CD patients) and 101,265 patients in the reference population. The incidence rate ratio of vertebral fractures in the IBD patients was 1.27 per 1,000 person-years (95% confidence interval [CI], 1.26-1.27). The risk of vertebral fracture was higher in CD and UC patients than in the matched reference group (hazard ratio [HR], 1.59; 95% CI, 1.31-1.92; P < 0.001 and HR, 1.26; 95% CI, 1.14-1.41; P < 0.001, respectively). In a multivariate analysis, the occurrence of vertebral fracture was associated with CD (HR, 1.31; 95% CI, 1.08-1.59; P = 0.006), older age (CD: HR, 1.09; 95% CI, 1.08-1.09; P < 0.001 and UC: HR, 1.09; 95% CI, 1.08-1.09; P < 0.001), female sex (CD: HR, 1.81; 95% CI, 1.63-2.01; P < 0.001 and UC: HR, 2.02; 95% CI, 1.83-2.22; P < 0.001), high Charlson Comorbidity Index (CCI) score (CD: HR, 1.42; 95% CI, 1.23-1.63; P < 0.001 and UC: HR, 1.46; 95% CI, 1.29-1.65, P < 0.001), and long-term steroid use (CD: HR, 3.71; 95% CI, 2.84-3.37; P < 0.001 and UC: HR, 3.88; 95% CI, 3.07-4.91; P < 0.001). The severity of vertebral fractures was associated with IBD (CD: HR, 1.82; 95% CI, 1.17-2.83; P = 0.008 and UC: HR, 1.49; 95% CI, 1.17-1.89; P < 0.001) and older age (HR, 1.06; 95% CI, 1.05-1.07; P < 0.001). CONCLUSION: Vertebral fractures occur frequently and more severely in IBD patients, particularly those with CD. Therefore, we suggest monitoring of bone density, regular vitamin D supply, and reducing the use of corticosteroids to prevent vertebral fractures in IBD patients who are older, female, or have comorbidities.

Predictive Validity of a New Triage System for Outcomes in Patients Visiting Pediatric Emergency Departments: A Nationwide Study in Korea.

Triage is essential for rapid and efficient intervention in patients visiting an emergency department. In Korea, since 2016, the Pediatric Korean Triage and Acuity Scale (PedKTAS) has been implemented nationwide for the triage of patients visiting pediatric emergency departments (PEDs). The aim of this study was to evaluate the validity of the PedKTAS in patients who visit PEDs. This study was a retrospective observational study of national registry data collected from all emergency medical centers and institutions throughout Korea. We analyzed data from patients aged <15 years who visited emergency departments nationwide from January 2016 to December 2019. The hospitalization and intensive care unit (ICU) admission rates were analyzed on the basis of triage level. In total, 5,462,964 pediatric patients were included in the analysis. The hospitalization rates for PedKTAS Levels 1-5, were 63.5%, 41.1%, 17.0%, 6.5%, and 3.7%, respectively, and were significantly different (p < 0.001). The ICU admission rates for PedKTAS Levels 1-5 were 14.4%, 6.0%, 0.3%, 0.1%, and 0.1%, respectively, and were significantly different (p < 0.001). The hospitalization and ICU admission rates were highest for PedKTAS Level 1, and differences were significant based on the level. We identified that the PedKTAS is suitable for predicting the emergency status of pediatric patients who visit PEDs.

Effect of COVID-19 on Emergency Department Visits by Pediatric Burn Patients in Korea: Retrospective Observational Study.

It's been over a year since the outbreak of the coronavirus disease (COVID-19), which is still a global public health challenge. Many countries have implemented social distancing to prevent the risk of infection with COVID-19. As a result, children spend more time at home. Home is where burns among children occur predominantly. We hypothesized that the changes in lifestyle due to the COVID-19 outbreak may have affected pediatric emergency department (PED) visits by children sustaining burn injuries. This study was a long-term multicenter observational study. Pediatric burn patients were defined in accordance with International Classification of Disease, Tenth Edition (ICD-10). We investigated the trend in PED weekly visits by pediatric burn patients before and after the outbreak of COVID-19 and trends in the proportion of visits according to burn severity based on segmented regression analysis. The data were adjusted for seasonality due to seasonal variation in the visits. Over the past 3 years, the proportion of pediatric burn patients tended to decrease. However, it increased in the fourth week of January 2020, when COVID-19 was first confirmed in Korea. In particular, the proportion of PED visits to pediatric burn patients with severe burns increased after the COVID-19 epidemic. Our study showed increases in the proportion of PED visits among pediatric burn patients due to the spread of COVID-19. Many of these burn accidents mainly occur at home, suggesting the need for parental intervention to prevent the risk of burn injuries among children.

Seven Days of Bismuth-Based Quadruple Therapy Is as Effective for the First-Line Treatment of Clarithromycin-Resistant Confirmed Helicobacter pylori Infection as 14 Days of Bismuth-Based Quadruple Therapy.

BACKGROUND/AIMS: Point mutations in the 23S ribosomal RNA gene have been associated with Helicobacter pylori (H. pylori) clarithromycin resistance and bismuth-based quadruple therapy (BQT) is one of the options for the treatment of clarithromycin-resistant H. pylori. Current H. pylori treatment guidelines recommend BQT for 10-14 days. This study aims to compare the eradication extents according to 7-day and 14-day BQT treatment for treatment-naïve clarithromycin-resistant confirmed H. pylori infection. METHODS: We retrospectively investigated treatment-naïve H. pylori infection cases from March 2019 to December 2020, where patients were treated with BQT. Clarithromycin resistance was identified with a dual-priming oligonucleotide-based multiplex polymerase chain reaction method. We reviewed a total of 126 cases. Fifty-three subjects were treated with a 7-day BQT regimen (7-day group), and 73 subjects were treated with a 14-day BQT regimen (14-day group). We evaluated the total eradication extent of the BQT and compared the eradication extents of the two study groups. RESULTS: Total eradication extent of H. pylori was 83.3% (105/126). The eradication extents of the two groups were as follows: 7-day group (81.1% (43/53)), 14-day group (84.9% (62/73), p = 0.572) by intention-to-treat analysis; 7-day group (95.6% (43/45)), 14-day group (92.5% (62/67), p = 0.518) by per-protocol analysis. The moderate or severe adverse event extents during the eradication were 30.2% (16/53) in the 7-day group and 19.2% (14/73) in the 14-day group (p = 0.152). CONCLUSIONS: The 7-day BQT regimen was as effective as the 14-day BQT regimen in the eradication of treatment-naïve clarithromycin-resistant H. pylori infection.

Impact of COVID-19 Pandemic on Children Visiting Emergency Department for Mental Illness: A Multicenter Database Analysis from Korea.

We aimed to identify changes in the proportion of pediatric emergency department (PED) visits due to mental illness during the coronavirus disease 2019 (COVID-19) pandemic. This was a retrospective observational study of visits to the PED at six university hospitals from January 2017 to December 2020. We included children aged 5−17 years who were diagnosed with a mental illness. We used segmented regression analysis to identify the change in the proportion of patients with mental illness. A total of 845 patients were included in the analysis. After the first case of COVID-19 was reported in Korea, the number of PED visits significantly decreased by 560.8 patients per week (95% confidence interval (CI): −665.3 to −456.3, p < 0.001). However, the proportion of patients with mental illness increased significantly, by 0.37% per week (95% CI: 0.04% to 0.70%, p = 0.03), at this time point. Subgroup analyses revealed that emotional disorders significantly increased by 0.06% per month (95% CI: 0.02% to 0.09%, p < 0.001) during the pandemic. Our study revealed that an increased proportion of patients with mental illness visited the PED during the COVID-19 pandemic. Specifically, we identified that the proportion of emotional disorders continues to rise during this pandemic.

Changes in the Clinical Characteristics of Kawasaki Disease After Coronavirus Disease (COVID-19) Pandemic: A Database Analysis.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic on Kawasaki disease (KD) has not yet been established. We investigated changes in the observed number and severity of KD cases and accompanying coronary artery complications during the COVID-19 pandemic in Korea. METHODS: This retrospective observational study included patients aged < 18 years with acute-phase KD diagnosed between March 2018 and February 2021. Data were extracted from the Clinical Data Warehouse that houses data from five affiliated university hospitals in Korea. We analyzed changes in the number of patient admissions and clinical characteristics, including cardiac complications, before and after the onset of the COVID-19 pandemic. RESULTS: A total of 475 admissions were included in the analysis. After March 2020, we observed a significant decrease of 33% in the number of hospitalizations for KD compared with the average number of hospitalizations during the previous 2 years. The number of admissions per month significantly decreased by 7.9 persons/month (95% confidence interval, -13.8 to -2.0; P < 0.05) compared with that before COVID-19. By contrast, the proportion of patients aged < 1 year with KD increased. The proportion of patients with refractory KD and the rate of cardiac complications did not change significantly. CONCLUSION: Since the onset of the COVID-19 pandemic, the total number of hospital admissions for KD has decreased in Korea. Although the proportion of admissions of infants aged < 1 year increased, no changes were observed in clinical courses and complications.

Changes in the Epidemiology and Causative Pathogens of Meningitis in Children After the Outbreak of the Coronavirus Disease 2019: A Multicenter Database Study.

Background: With the outbreak of the COVID-19 pandemic, non-pharmaceutical interventions such as social distancing have been implemented worldwide, and a decrease in other infectious diseases has been reported as an unexpected benefit. However, to date, studies are lacking regarding the effects of the COVID-19 pandemic on neuroinfectious diseases; therefore, we aimed to determine the effects of the COVID-19 pandemic on the incidence of meningitis, which is the most common infectious disease in children. Methods: This retrospective study used electronic medical record data from five university hospitals located in the metropolitan cities in Korea. This study included patients aged <18 years who were diagnosed with meningitis between January 2017 and December 2020. We analyzed the clinical characteristics of patients with meningitis and changes in the incidence and causative pathogens of meningitis before and after the COVID-19 outbreak. Results: The study included 677 patients with meningitis. Following the outbreak of COVID-19 in Korea in January 2020, the incidence of childhood meningitis significantly decreased and seasonal changes noted yearly disappeared. There was a difference in the age distribution of patients with meningitis. The incidence of meningitis decreased significantly in children aged >5 years, and the incidence in children <5 years of age relatively increased (p < 0.001). In addition, there was a notable decrease in the cases of suspected meningitis (p < 0.001). The incidence of enteroviral meningitis, the most common cause of meningitis, significantly decreased. Conclusion: After the COVID-19 outbreak, the incidence of childhood meningitis significantly decreased with the implementation of non-pharmaceutical interventions. Absence of enteroviral meningitis and decrease in the proportion of patients aged ≥5 years with meningitis having mild symptoms were noted. Consequently, it can be concluded that the non-pharmaceutical interventions (NPIs) instituted to prevent the spread of COVID-19 had some effect on reducing the incidence of meningitis.

One-year changes in the pediatric emergency department caused by prolonged coronavirus disease 2019 pandemic.

BACKGROUND: With the coronavirus disease 2019 (COVID-19) pandemic lasting for more than a year, it is imperative to identify the associated changes in the use of emergency medical care for efficient operation of the pediatric emergency department (PED). This study was conducted to determine the long-term impact of the COVID-19 pandemic on patterns of PED visits. METHODS: This is a retrospective observational study of visits to the PED of six hospitals, between January 1, 2017, and December 31, 2020. We compared changes in the characteristics of patients before and during the COVID-19 pandemic. RESULTS: A total of 245 022 visits were included in this analysis. After the first case of COVID-19 was reported in Korea, we observed a significant decrease (54.2%) in PED visits compared with the annual average number of visits in the previous 3 years. Since then, the weekly number of PED visits decreased by 11.9 person/week (95% CI: -15.3--8.4, P < 0.001), which included an increase of 0.21% (95% CI: 0.15%-0.26%, P < 0.001) per week in high acuity patients. From 2017 to 2020, the proportion of infectious respiratory diseases by year was 25.9%, 27.0%, 28.6%, and 16.3%, respectively, demonstrating a significant decrease in 2020 (P < 0.001). CONCLUSIONS: During the COVID-19 pandemic, the number of patient visits to PEDs continues to decline, especially among those with infectious diseases. However, the disease severity of patients has gradually increased. There has been a change in the characteristics of visits to PEDs after COVID-19 which will require an appropriate response from a long-term perspective.

Impact of Covid-19 on the Visit of Pediatric Patients with Injuries to the Emergency Department in Korea.

The total number of pediatric emergency department (PED) visitors has decreased worldwide since the coronavirus disease (COVID-19) outbreak. We hypothesized that this might also affect the number of PED visits due to injuries. Therefore, we investigated these changes in PED visits after the COVID-19 outbreak through a long-term multicenter observational study. We assessed the changes in the proportion of injured pediatric patients' weekly visits and the trend in the rate changes since the COVID-19 epidemic began by segmented regression analysis. We also evaluated the weekly change in the distribution of detailed diagnostic codes among pediatric patients with injuries before and after the COVID-19 pandemic. The proportion of injury-related PED visits increased when COVID-19 was first confirmed in Korea. After the COVID-19 epidemic, the proportion of foreign body ingestions and fracture patients among all pediatric patients with injuries increased significantly every week. The changes in the proportion of injured pediatric patients after the COVID-19 outbreak may have been the result of social distancing to prevent the spread of the virus. The risk of pediatric infections decreased but the risk of injury remained. Therefore, parents should take precautions to prevent infectious diseases and be careful to prevent children's injuries at home.

Atg7-dependent canonical autophagy regulates the degradation of aquaporin 2 in prolonged hypokalemia.

Prolonged hypokalemia induces a decrease of urinary concentrating ability via down-regulation of aquaporin 2 (AQP2); however, the precise mechanisms remain unknown. To investigate the role of autophagy in the degradation of AQP2, we generated the principal cell-specific Atg7 deletion (Atg7Δpc) mice. In hypokalemic Atg7-floxed (Atg7f/f) mice, huge irregular shaped LC3-positive autophagic vacuoles accumulated mainly in inner medullary collecting duct (IMCD) cells. Total- and pS261-AQP2 were redistributed from apical and subapical domains into these vacuoles, which were not co-localized with RAB9. However, in the IMCD cells of hypokalemic Atg7Δpc mice, these canonical autophagic vacuoles were markedly reduced, whereas numerous small regular shaped LC3-negative/RAB9-positive non-canonical autophagic vacuoles were observed along with diffusely distributed total- and pS261-AQP2 in the cytoplasm. The immunoreactivity of pS256-AQP2 in the apical membrane of IMCD cells was markedly decreased, and no redistribution was observed in both hypokalemic Atg7f/f and Atg7Δpc mice. These findings suggest that AQP2 down regulation in hypokalemia was induced by reduced phosphorylation of AQP2, resulting in a reduction of apical plasma labeling of pS256-AQP2 and degradation of total- and pS261-AQP2 via an LC3/ATG7-dependent canonical autophagy pathway.

Notch signaling in the collecting duct regulates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction in mice.

Background/Aims: Mind bomb-1 (Mib1) encodes an E3 ubiquitin ligase, which is required for the initiation of Notch signaling. Recently, it was demonstrated that the renal collecting duct plays an important role in renal fibrosis. Here, we investigated the role of Notch signaling in renal fibrosis using conditional knockout mice with the specific ablation of Mib1 in renal collecting duct principal cells. METHODS: Mib1-floxed mice (Mib1f/f) were crossed with aquaporin 2 (AQP2)-Cre mice in order to generate principal cell-specific Mib1 knockout mice (Mib1f/f :AQP2-Cre+). Unilateral ureteral obstruction (UUO) was performed, and mice were sacrificed 7 days after UUO. RESULTS: After performing the UUO, renal tubulointerstitial fibrosis and the expression of transforming growth factor ß were markedly enhanced in the obstructed kidneys of Mib1f/f mice compared with the sham-operated kidney of Mib1f/f mice. These changes were shown to be even more pronounced in the obstructed kidneys of Mib1f/f :AQP2-Cre+ mice than in those of the Mib1f/f mice . Furthermore, the number of TUNNEL-positive cells in renal collecting duct was higher in the obstructed kidneys of Mib1f/f :AQP2-Cre+ mice than in the kidneys of Mib1f/f mice. Conclusions: Notch signaling in the renal collecting duct plays an important role in the regulation of renal tubulointerstitial fibrosis and apoptosis after UUO.

The Hippo-Salvador signaling pathway regulates renal tubulointerstitial fibrosis.

Renal tubulointerstitial fibrosis (TIF) is the final pathway of various renal injuries that result in chronic kidney disease. The mammalian Hippo-Salvador signaling pathway has been implicated in the regulation of cell proliferation, cell death, tissue regeneration, and tumorigenesis. Here, we report that the Hippo-Salvador pathway plays a role in disease development in patients with TIF and in a mouse model of TIF. Mice with tubular epithelial cell (TEC)-specific deletions of Sav1 (Salvador homolog 1) exhibited aggravated renal TIF, enhanced epithelial-mesenchymal transition-like phenotypic changes, apoptosis, and proliferation after unilateral ureteral obstruction (UUO). Moreover, Sav1 depletion in TECs increased transforming growth factor (TGF)-ß and activated ß-catenin expression after UUO, which likely accounts for the abovementioned enhanced TEC fibrotic phenotype. In addition, TAZ (transcriptional coactivator with PDZ-binding motif), a major downstream effector of the Hippo pathway, was significantly activated in Sav1-knockout mice in vivo. An in vitro study showed that TAZ directly regulates TGF-ß and TGF-ß receptor II expression. Collectively, our data indicate that the Hippo-Salvador pathway plays a role in the pathogenesis of TIF and that regulating this pathway may be a therapeutic strategy for reducing TIF.

Descending thin limb of the intermediate loop expresses both aquaporin 1 and urea transporter A2 in the mouse kidney.

A new intermediate type of Henle's loop has been reported that it extends into the inner medulla and turns within the first millimeter beyond the outer medulla. This study aimed to identify the descending thin limb (DTL) of the intermediate loop in the adult C57Bl/6 mouse kidney using aquaporin 1 (AQP1) and urea transporter A2 (UT-A2) antibodies. In the upper part of the inner stripe of the outer medulla (ISOM), AQP1 was expressed strongly in the DTL with type II epithelium of the long loop, but not in type I epithelium of the short loop. The DTL of the intermediate loop exhibited weak AQP1 immunoreactivity. UT-A2 immunoreactivity was not observed in the upper part of any DTL type. AQP1 expression was similar in the upper and middle parts of the ISOM. UT-A2 expression was variable, being expressed strongly in the DTL with type I epithelium of the short loop, but not in type II epithelium of the long loop. In the innermost part of the ISOM, AQP1 was expressed only in type III epithelium of the long loop. UT-A2-positive and UT-A2-negative cells were intermingled in type I epithelium of the intermediate loop, but were not observed in type III epithelium of the long loop. UT-A2-positive DTLs of the intermediate loop extended into the UT-A2/AQP1-negative type I epithelium in the initial part of the inner medulla. These results demonstrate that the DTL of the intermediate loop is composed of type I epithelium and expresses both AQP1 and UT-A2. The functional role of the DTL of the intermediate loop may be distinct from the short or long loops.