Twenty-Five Year Trend Change in the Etiology of Pediatric Invasive Bacterial Infections in Korea, 1996–2020

Background@#The coronavirus disease-2019 (COVID-19) pandemic has contributed to the change in the epidemiology of many infectious diseases. This study aimed to establish the pre-pandemic epidemiology of pediatric invasive bacterial infection (IBI). @*Methods@#A retrospective multicenter-based surveillance for pediatric IBIs has been maintained from 1996 to 2020 in Korea. IBIs caused by eight bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species) in immunocompetent children > 3 months of age were collected at 29 centers. The annual trend in the proportion of IBIs by each pathogen was analyzed. @*Results@#A total of 2,195 episodes were identified during the 25-year period between 1996 and 2020. S. pneumoniae (42.4%), S. aureus (22.1%), and Salmonella species (21.0%) were common in children 3 to 59 months of age. In children ≥ 5 years of age, S. aureus (58.1%), followed by Salmonella species (14.8%) and S. pneumoniae (12.2%) were common. Excluding the year 2020, there was a trend toward a decrease in the relative proportions of S. pneumoniae (rs = −0.430, P = 0.036), H. influenzae (rs = −0.922, P 3 months of age. These findings can be used as the baseline data to navigate the trend in the epidemiology of pediatric IBI in the post COVID-19 era.

Assessment of Esophageal Reconstruction via Bioreactor Cultivation of a Synthetic Scaffold in a Canine Model

Objectives@#. Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals that requires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment of peristalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaffold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model. @*Methods@#. We fabricated a novel double-layered scaffold as a tissue-engineered esophagus using an electrospinning technique. Prior to transplantation, human-derived mesenchymal stem cells were seeded into the lumen of the scaffold, and bioreactor cultivation was performed to enhance cellular reactivity. After 3 days of cultivation using the bioreactor system, tissue-engineered artificial esophagus was transplanted into a partial esophageal defect (5×3 cm-long resection) in a canine model. @*Results@#. Scanning electron microscopy (SEM) showed that the electrospun fibers in a tubular scaffold were randomly and circumferentially located toward the inner and outer surfaces. Complete recovery of the esophageal mucosa was confirmed by endoscopic analysis and SEM. Esophagogastroduodenoscopy and computed tomography also showed that there were no signs of leakage or stricture and that there was a normal lumen with complete epithelialization. Significant regeneration of the mucosal layer was observed by keratin-5 immunostaining. Alpha-smooth muscle actin immunostaining showed significantly greater esophageal muscle regeneration at 12 months than at 6 months. @*Conclusion@#. Custom-designed bioreactor cultured electrospun polyurethane scaffolds can be a promising approach for esophageal tissue engineering.

Giant Coronary Artery Aneurysm with Thrombosis Complicated in a Patient with Idiopathic Hypereosinophilic Syndrome

Idiopathic hypereosinophilic syndrome (iHES) is a rare systemic disease that is characterized by persistent peripheral eosinophilia (absolute eosinophil count ≥1500/uL) for more than 6 months, with end-organ damage and absence of a primary cause for eosinophilia. Coronary artery aneurysm (CAA) is a rare but life-threatening complication. Here, we report a case of CAA with thrombosis in a patient with iHES in whom the disease activity was well-controlled (eosinophil count <500/uL) for several years. Despite modest control of the disease activity, giant CAA can be associated with iHES; and therefore, close surveillance and monitoring for the development of complications is warranted.

Clinical Characteristics and Outcomes of Children With SARS-CoV-2 Infection During the Delta and Omicron VariantDominant Periods in Korea

Background@#Data on the clinical characteristics of pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection are limited. We aimed to evaluate the clinical features and outcomes of children with SARS-CoV-2 infection before and after omicron variant dominance in Korea. @*Methods@#A multicenter retrospective cohort study was conducted in hospitalized patients aged ≤ 18 years with laboratory-confirmed SARS-CoV-2 infection at five university hospitals in South Korea. The study periods were divided into the delta (from August 23, 2021 to January 2, 2022) and omicron (from January 30 to March 31, 2022). @*Results@#In total, 612 hospitalized patients were identified (211, delta; 401, omicron). During the omicron and delta periods, the proportions of individuals with serious illness (moderate, severe, and critical severity) were 21.2% and 11.8%, respectively (P = 0.034). Compared with the delta period, the proportions of patients with moderate illness increased significantly in the age groups of 0–4 years (14.2% vs. 3.4%) and 5–11 years (18.6% vs. 4.2%) during the omicron period. During the two periods, the proportions of patients with complex chronic diseases (delta, 16.0% vs. 4.3%, P = 0.040; omicron, 27.1% vs. 12.7%; P= 0.002), respiratory diseases except for asthma (delta, 8.0% vs. 0.0%, P = 0.013; omicron, 9.4% vs. 1.6%; P = 0.001), and neurologic diseases (delta, 28.0% vs. 3.2%, P < 0.001; omicron, 40.0% vs. 5.1%, P < 0.001) were significantly higher in patients with serious illness than in those with nonserious illness. During the delta period, the risk for serious illness was higher among patients with obesity (adjusted odds ratio [aOR], 8.18; 95% confidence interval [CI], 2.80–27.36) and neurologic diseases (aOR, 39.43; 95% CI, 6.90–268.3) and aged 12–18 years (aOR, 3.92; 95% CI, 1.46–10.85). However, the presence of neurologic disease (aOR, 9.80; 95% CI, 4.50–22.57) was the only risk factor for serious illness during the omicron period. During the omicron period, the proportions of patients with croup (11.0% vs. 0.5%) and seizures (13.2% vs. 2.8%) increased significantly compared with the delta period. @*Conclusion@#Compared with the delta period, the proportions of young children and patients with complex comorbidities were higher during the omicron period in Korea. Patients

Safety and Efficacy of Everolimus-Eluting Bioresorbable Vascular Scaffold Versus Second-Generation Drug-Eluting Stents in Real-World Practice

Background@#The risk of device thrombosis and device-oriented clinical outcomes with bioresorbable vascular scaffold (BVS) was reported to be significantly higher than with contemporary drug-eluting stents (DESs). However, optimal device implantation may improve clinical outcomes in patients receiving BVS. The current study evaluated mid-term safety and efficacy of Absorb BVS with meticulous device optimization under intravascular imaging guidance. @*Methods@#The SMART-REWARD and PERSPECTIVE-PCI registries in Korea prospectively enrolled 390 patients with BVS and 675 patients with DES, respectively. The primary endpoint was target vessel failure (TVF) at 2 years and the secondary major endpoint was patientoriented composite outcome (POCO) at 2 years. @*Results@#Patient-level pooled analysis evaluated 1,003 patients (377 patients with BVS and 626 patients with DES). Mean scaffold diameter per lesion was 3.24 ± 0.30 mm in BVS group.Most BVSs were implanted with pre-dilatation (90.9%), intravascular imaging guidance (74.9%), and post-dilatation (73.1%) at proximal to mid segment (81.9%) in target vessel.Patients treated with BVS showed comparable risks of 2-year TVF (2.9% vs. 3.7%, adjusted hazard ratio [HR], 1.283, 95% confidence interval [CI], 0.487–3.378, P = 0.615) and 2-year POCO (4.5% vs. 5.9%, adjusted HR, 1.413, 95% CI, 0.663–3.012,P = 0.370) than those with DES. The rate of 2-year definite or probable device thrombosis (0.3% vs. 0.5%, P = 0.424) was also similar. The sensitivity analyses consistently showed comparable risk of TVF and POCO between the 2 groups. @*Conclusion@#With meticulous device optimization under imaging guidance and avoidance of implantation in small vessels, BVS showed comparable risks of 2-year TVF and device thrombosis with DES.

Impact of Atrial Fibrillation on Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI): The K-TAVI Registry

Purpose@#The incidence and prognostic implications of atrial fibrillation (AF) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) are controversial, especially for Korean patients. Furthermore, the pattern of antithrombotic therapy for these patients is unknown. The present study sought to identify the impact of AF on Korean patients undergoing TAVI and demonstrate the status of antithrombotic therapy for these patients. @*Materials and Methods@#A total of 660 patients who underwent TAVI for severe AS were recruited from the nationwide K-TAVI registry in Korea. The enrolled patients were stratified into sinus rhythm (SR) and AF groups. The primary endpoint was all-cause death at 1-year. @*Results@#AF was recorded in 135 patients [pre-existing AF 108 (16.4%) and new-onset AF 27 (4.1%)]. The rate of all-cause death at 1 year was significantly higher in patients with AF than in those with SR [16.2% vs. 6.4%, adjusted hazard ratio (HR): 2.207, 95% confidence interval (CI): 1.182–4.120, p=0.013], regardless of the onset timing of AF. The rate of new pacemaker insertion at 1 year was also significantly higher in patients with AF than in those with SR (14.0% vs. 5.5%, adjusted HR: 3.137, 95%CI: 1.621–6.071, p=0.001).Among AF patients, substantial number of patients received the combination of multiple antithrombotic agents (77.8%), and the most common combination was that of aspirin and clopidogrel (38.1%). @*Conclusion@#AF was an independent predictor of 1-year mortality and new pacemaker insertion in Korean patients undergoing TAVI.

Etiology and Risk Factors of Community-Acquired Pneumonia in Hospitalized Children During the COVID-19 Pandemic in South Korea

Purpose@#This study aimed to identify the etiology and risk factors of community-acquired pneumonia (CAP) requiring hospitalization in Korean children during the coronavirus disease 2019 (COVID-19) pandemic. @*Methods@#Clinical information of children admitted with CAP to Seoul National University Children’s Hospital (SNUCH) between January 1, 2021, and February 28, 2022, was retrospectively collected and analyzed. In addition, the etiologic diagnosis and demographic data of children with CAP who were discharged at the other seven hospitals between January and February 2022 were collected. Pneumonia was diagnosed using strict criteria comprising clinical symptoms, physical examination findings, and chest radiographic findings. @*Results@#Among 91 children hospitalized with CAP at SNUCH during the 14-month period, 68.4% were aged <5 years and 79.1% had underlying diseases. Among the 95 CAP cases, respiratory assistance was required in 70.5%, and the use of a ventilator was required in 20.0%.A total of five patients expired, all of whom were either immunocompromised or had underlying neurological diseases. Neurological diseases and immunosuppression were significantly correlated with respiratory assistance (P=0.003) and death (P=0.014). A total of 55% of the detected respiratory pathogens were viruses, the most common of which was rhinovirus at 35.9%. Among the 169 children hospitalized for CAP at the eight institutions, ≥1 respiratory virus was detected in 92.3%, among which respiratory syncytial virus (79.8%) was the most prevalent. @*Conclusions@#Even during the COVID-19 pandemic, Korean children were hospitalized with CAP caused by seasonal respiratory viral pathogens. Although atypical and pyogenic bacteria were not detected, continuous clinical monitoring and further prospective studies should be conducted.

Intraindividual Comparison of MRIs with Extracellular and Hepatobiliary Contrast Agents for the Noninvasive Diagnosis of Hepatocellular Carcinoma Using the Korean Liver Cancer Association–National Cancer Center 2022 Criteria / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The aim of the present study was to evaluate the per-lesion sensitivity and specificity of the Korean Liver Cancer Association–National Cancer Center (KLCA-NCC) 2022 criteria for the noninvasive diagnosis of hepatocellular carcinoma (HCC), with intraindividual comparison of the diagnostic performance of magnetic resonance imaging with extracellular agents (ECA-MRI) and hepatobiliary agents (HBA-MRI). @*Materials and Methods@#Patients at high risk for HCC who were referred to a tertiary academic institution for hepatic lesions with size ≥ 10 mm between July 2019 and June 2022 were enrolled. A total of 91 patients (mean age, 58.1 years; 76 men and 15 women) with 118 lesions who underwent both ECA-MRI and HBA-MRI were eligible for final analysis. The per-lesion sensitivities and specificities of the KLCA-NCC 2022 criteria using ECA-MRI and HBA-MRI were compared using McNemar’s test. @*Results@#The 118 lesions were 93 HCCs, 4 non-HCC malignancies, and 21 benign lesions. On HBA-MRI, the “definite” HCC category showed significantly higher sensitivity than ECA-MRI (78.5% vs. 58.1%, p 0.999). For “probable” or “definite” HCC categories, there were no differences in the sensitivity (84.9% vs. 84.9%, p > 0.999) and specificity (84.0% vs. 84.0%, p > 0.999) between ECA-MRI and HBA-MRI. @*Conclusion@#The “definite” HCC category of the KLCA-NCC 2022 criteria showed higher sensitivity in diagnosing HCC on HBA-MRI compared with ECA-MRI, without compromising specificity. There were no significant differences in the sensitivity and specificity of “probable” or “definite” HCC categories according to ECA-MRI and HBA-MRI.

Myelin Content in Mild Traumatic Brain Injury Patients with Post-Concussion Syndrome: Quantitative Assessment with a Multidynamic Multiecho Sequence

Objective@#This study aimed to explore the myelin volume change in patients with mild traumatic brain injury (mTBI) with post-concussion syndrome (PCS) using a multidynamic multiecho (MDME) sequence and automatic whole-brain segmentation. @*Materials and Methods@#Forty-one consecutive mTBI patients with PCS and 29 controls, who had undergone MRI including the MDME sequence between October 2016 and April 2018, were included. Myelin volume fraction (MVF) maps were derived from the MDME sequence. After three dimensional T1-based brain segmentation, the average MVF was analyzed at the bilateral cerebral white matter (WM), bilateral cerebral gray matter (GM), corpus callosum, and brainstem. The Mann–Whitney U-test was performed to compare MVF and myelin volume between patients with mTBI and controls. Myelin volume was correlated with neuropsychological test scores using the Spearman rank correlation test. @*Results@#The average MVF at the bilateral cerebral WM was lower in mTBI patients with PCS (median [interquartile range], 25.2% [22.6%–26.4%]) than that in controls (26.8% [25.6%–27.8%]) (p = 0.004). The region-of-interest myelin volume was lower in mTBI patients with PCS than that in controls at the corpus callosum (1.87 cm3 [1.70–2.05 cm3 ] vs. 2.21 cm3 [1.86– 3.46 cm3 ]; p = 0.003) and brainstem (9.98 cm3 [9.45–11.00 cm3 ] vs. 11.05 cm3 [10.10–11.53 cm3 ]; p = 0.015). The total myelin volume was lower in mTBI patients with PCS than that in controls at the corpus callosum (0.45 cm3 [0.39–0.48 cm3 ] vs. 0.48 cm3 [0.45–0.54 cm3 ]; p = 0.004) and brainstem (1.45 cm3 [1.28–1.59 cm3 ] vs. 1.54 cm3 [1.42–1.67 cm3 ]; p = 0.042). No significant correlation was observed between myelin volume parameters and neuropsychological test scores, except for the total myelin volume at the bilateral cerebral WM and verbal learning test (delayed recall) (r = 0.425; p = 0.048). @*Conclusion@#MVF quantified from the MDME sequence was decreased at the bilateral cerebral WM in mTBI patients with PCS. The total myelin volumes at the corpus callosum and brainstem were decreased in mTBI patients with PCS due to atrophic changes.

Risk Factors for Severe COVID-19 in Children: A Systematic Review and Meta-Analysis

Background@#Coronavirus disease 2019 (COVID-19) has been the most important global issue since December 2019. Although the clinical course of COVID-19 is known to be milder in children than in adults, associated hospitalizations among children have increased since the emergence of contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the achievement of a high vaccination rate in adults. Considering these global and domestic situations, we believe that risk stratification in children with COVID-19 is urgently needed for decision making regarding hospitalization priority in children infected with SARS-CoV-2 and vaccination priority against COVID-19. @*Methods@#This systematic review and meta-analysis was performed by comprehensively searching the PubMed, EMBASE, Scopus and KoreaMed databases through August 25, 2021.The criteria for enrollment were “severe COVID-19” as poor outcomes (intensive care unit admission, invasive mechanical ventilation, and/or death) and underlying comorbidities before SARS-CoV-2 infection. @*Results@#Among 872 screened studies, 17 articles were included in the systematic review, and 10 articles were included in the meta-analysis. Neonate (risk ratio [RR], 2.69; 95% confidence interval [CI], 1.83–3.97), prematurity in young infants (RR, 2.00; 95% CI, 1.63–2.46), obesity (RR, 1.43; 95% CI, 1.24–1.64), diabetes (RR, 2.26; 95% CI, 1.95–2.62), chronic lung disease (RR, 2.62; 95% CI, 1.71–4.00), heart disease (RR, 1.82; 95% CI, 1.58–2.09), neurologic disease (RR, 1.18; 95% CI, 1.05–1.33), and immunocompromised status (RR, 1.44; 95% CI, 1.01–2.04) were significant risk factors for severe COVID-19 in children. In the subgroup analysis, age younger than 3 months (RR, 0.26; 95% CI, 0.11–0.66), asthma (RR, 1.08; 95% CI, 0.98–1.20), and neurodevelopmental disorders (RR, 0.88; 95% CI, 0.75–1.04) were not risk factors for severe COVID-19. @*Conclusion@#Children with comorbidities such as obesity, diabetes, heart disease, chronic lung diseases other than asthma, seizure disorders, and an immunocompromised status had a high prevalence of severe COVID-19. Neonate and premature infants had a high risk of severe COVID-19. Defining the high-risk group for severe COVID-19 could help to guide hospital admission and priority for vaccination against SARS-CoV-2.

Clavicular Tunnel Complications after Coracoclavicular Reconstruction in Acute Acromioclavicular Dislocation: Coracoid Loop versus Coracoid Tunnel Fixation

Background@#The purpose of this study was to compare clavicular tunnel complications after coracoclavicular (CC) reconstruction between a coracoid loop fixation group and a coracoid tunnel fixation group. We hypothesized that clavicular tunnel complications would be more common in the coracoid loop group. @*Methods@#This retrospective study evaluated 24 patients who underwent CC reconstruction using coracoid tunnel fixation (n = 14) and coracoid loop fixation (n = 10). Radiographic measurements included the CC distance and clavicular tunnel diameter. Clavicular tunnel complications such as tunnel widening and clavicular tunnel fractures were investigated. Clinical outcomes were assessed using the American Shoulder and Elbow Surgeons Shoulder score and the University of California at Los Angeles Shoulder score. @*Results@#The mean follow-up period was 17.5 months (range, 11–38 months). The final clavicular tunnel diameter and the increase in the clavicular tunnel diameter in millimeter and percentage were significantly greater in the coracoid loop group than in the coracoid tunnel group (all p < 0.05). Clavicular tunnel widening more than 100% was found in 5 patients, all belonging to the coracoid loop group. Clavicular tunnel fractures occurred in 3 patients (all in the coracoid loop group). Fracture was associated with severe tunnel widening (more than 100% increase). The mean value of the final clavicular tunnel diameter in patients with fractures was significantly larger than that in patients without (12.7 ± 3.3 mm vs. 8.4 ± 1.5 mm, p = 0.016). @*Conclusions@#Clavicular tunnel complications such as significant tunnel widening and fractures after CC reconstructions in acromioclavicular dislocations were common with the coracoid loop fixation technique. A greater clavicular tunnel widening and resultantly enlarged tunnel diameter might increase the risk of fracture through the clavicular tunnel.

Exoskeleton-assisted Gait Training in Spinal Disease With Gait Disturbance / 대한신경손상학회지

Objective@#Gait impairment reduces a patient’s quality of life. Exoskeletons and wearable robotics enable patients with gait disturbance to stand up and walk. An exoskeleton was developed for use in patients with stroke and spinal cord injuries. This study aimed to evaluate the effectiveness of overground exoskeleton-assisted gait training (OEGT) in spine diseases with gait disturbance. @*Methods@#This was a single-group preliminary study. Five participants with gait disorders because of root dysfunction accompanying spinal stenosis were included in this study. All participants underwent surgical treatment and an exoskeleton training protocol scheduled for 2 or 3 days per week for 4 weeks. Each session was 60 minutes. Clinical tests were performed before (T1) and at the end of the training (T2). @*Results@#One patient dropped out of the study because of medical issues that were not associated with the exoskeleton. Exoskeleton-assisted rehabilitation was feasible for all participants. All participants showed positive changes in gait performance, balance, proximal muscle strength, psychological state, and satisfaction with the rehabilitation. However, there was no significant improvement in neurological deficits. @*Conclusion@#OEGT is a feasible rehabilitation method for patients with gait disorders caused by degenerative spinal disease.

Shift in Clinical Epidemiology of Human Parainfluenza Virus Type 3 and Respiratory Syncytial Virus B Infections in Korean Children Before and During the COVID-19 Pandemic:A Multicenter Retrospective Study

Background@#Parainfluenza virus type 3 (PIV3) and respiratory syncytial virus (RSV) B epidemics occurred in South Korea in late 2021. We investigated epidemiological changes of PIV3 and RSV B infections in Korean children before and during the coronavirus disease 2019 (COVID-19) pandemic. @*Methods@#In this multicenter retrospective study, we enrolled patients aged less than 19 years with PIV3 or RSV infection in four university hospitals from January 2018 to January 2022. Demographic and clinical data were extracted from the subject’s medical records and analyzed for each virus. @*Results@#A total of 652 children with PIV3 were identified including three epidemics: 216 in 2018, 260 in 2019, and 167 in 2021. Among 627 RSV B cases, 169 were identified in 2017/2018, 274 in 2019/2020, and 115 in 2021/2022. The peak circulation of PIV3 and RSV B epidemics were delayed by 6 and 2 months, respectively, in 2021, compared with those in the pre-COVID-19 period. The median age of PIV3 infections increased in 2021 (21.5 months in 2021 vs. 13.0–14.0 in 2018–2019; P < 0.001), whereas that of RSV B infections remained unchanged (3.6–4.0 months). During the COVID-19 pandemic, less frequent hospitalization rates were observed for both PIV3 and RSV B infections, but more children needed respiratory assistance for RSV B infection in 2021/2022 epidemic (32.5%) than before (14.7–19.4%, P = 0.014). @*Conclusion@#We observed changes in the epidemiology and clinical presentation of PIV3 and RSV B infections in Korean children during the COVID-19 pandemic.

Genetic, Clinicopathological, and Radiological Features of Intrahepatic Cholangiocarcinoma with Ductal Plate Malformation Pattern

Background/Aims@#Intrahepatic cholangiocarcinoma (iCCA) with a ductal plate malformation (DPM) pattern is a recently recognized rare variant. The genomic profile of iCCA with DPM pattern needs to be elucidated. @*Methods@#Cases of iCCA with DPM pattern were retrospectively reviewed based on the medical records, pathology slides, and magnetic resonance imaging (MRI) reports collected between 2010 to 2019 at a single center. Massive parallel sequencing was performed for >500 cancerrelated genes. @*Results@#From a total of 175 iCCAs, five (2.9%) cases of iCCA with DPM pattern were identified. All cases were of the small duct type, and background liver revealed chronic B viral or alcoholic hepatitis. Three iCCAs with DPM pattern harbored MRI features favoring the diagnosis of hepatocellular carcinoma, whereas nonspecific imaging features were observed in two cases. All patients were alive without recurrence during an average follow-up period of 57 months. Sequencing data revealed 64 mutated genes in the five cases, among which FGFR2 and PTPRT were most frequently mutated (three cases each) including an FGFR2-TNC fusion in one case. Mutations in ARID1A and CDKN2A were found in two cases, and mutations in TP53, BAP1, ATM, NF1, and STK11 were observed in one case each. No IDH1, KRAS, or PBRM1 mutations were found. @*Conclusions@#iCCAs with DPM pattern have different clinico-radio-pathologic and genetic characteristics compared to conventional iCCAs. Moreover, FGFR2 and FGFR2 variants were identified. Altogether, these findings further suggest that iCCA with DPM pattern represents a specific subtype of small duct type iCCA.

Local Drug Delivery Strategies for Glioblastoma Treatment

Glioblastoma multiforme (GBM) is a brain tumor notorious for its malignancy. The key reason for the limited efficacy of standard treatment is the high recurrence rate of GBM, even after surgical resection. Hence, intensive postsurgical chemical therapies, such as the systemic delivery of various drugs and/ or drug combinations, are typically followed after surgery. However, overcoming the blood-brain barrier by systemic administration to efficiently deliver drugs to the brain tumor remains a daunting goal. Therefore, various local drug delivery methods showing potential for improved therapeutic efficacy have been proposed. In particular, the recent application of electronic devices for the controlled delivery of chemotherapy drugs to GBM tissue has attracted attention. We herein review the recent progress of local drug delivery strategies, including electronics-assisted strategies, at the research and commercial level. We also present a brief discussion of the unsolved challenges and future research direction of localized chemotherapy methods for GBM.

Therapeutics in the Treatment of COVID-19 for Children and Adolescents

Coronavirus disease 2019 (COVID-19) presents as a mild-to-moderate respiratory illness in most children. However, a small proportion of children with COVID-19 develop severe or critical illnesses. Although pediatric clinical trials for the treatment of COVID-19 are sparse, some drugs are available for children and adolescents with severe COVID-19. This review summarizes clinical data focusing on antiviral agents and immunomodulators for use in treating COVID-19. In addition, current recommendations for therapeutics for children and adolescents with COVID-19 are discussed.

Delphi Survey for COVID-19 Vaccination in Korean Children Between 5 and 11 Years Old

Purpose@#During the coronavirus disease 2019 (COVID-19) pandemic, we conducted a Delphi survey that included the experts from the field of COVID-19 immunization in children aged 5–11 years. The aim was to organize collective expert opinions on COVID-19 vaccination in young children in the Republic of Korea, and so thus assist the vaccination policy. @*Methods@#The panels included pediatric infectious disease specialists, preventive medicine experts, infectious disease physicians, and COVID-19 vaccine experts consulting the Ministry of Health and Welfare. The Delphi survey was conducted online using a questionnaire from February 14 to February 27, 2022. @*Results@#The Delphi panels agreed that children were vulnerable to COVID-19, and the severity of illness was modest. Furthermore the panels reported that children with chronic illness were more susceptible to a worsening clinical course. There were generally positive opinions on the effectiveness of COVID-19 vaccination in children aged 5–11 years, and experts gathered a slightly positive opinion that the adverse events of pediatric COVID-19 were not numerous. The benefits of COVID-19 vaccination were evaluated at a level similar to the potential risks in children.Currently, the only approved mRNA platform vaccine in children seemed to be sustainable; however, the recombinant protein platform COVID-19 vaccines were evaluated as better options. @*Conclusions@#Due to the surge of the Omicron variant and an increase in pediatric cases, the COVID-19 vaccination in young children may have to be considered. Panels had neutral opinions regarding the COVID-19 vaccination in children aged 5–11 years. Thus monitoring of the epidemiology and the data about the safety of COVID-19 vaccination should be continued.

Expert Consensus on COVID-19 Vaccination in Korean Adolescents:A Modified Delphi Survey

The effectiveness of coronavirus disease 2019 (COVID-19) vaccines had been shown in many studies in adult population, however, the real-world evidence in the childhood population was scarce. We aimed to organize the collective expert’s opinions on adolescent vaccination against COVID-19 in Korea, therefore to guide the vaccination policy in the setting of available evidence. The Delphi panels responded that adolescents were greatly impacted by the quarantine measures, and COVID-19 is an important health problem for adolescents.Panels responded that in general, the benefits of the COVID-19 vaccine overweigh the potential risks in Korean adolescents. Continuing monitoring of available data is needed to provide the best vaccination practices in adolescents guided by the updated evidence.

Circulating Cancer Stem Cells Expressing EpCAM/CD90 in Hepatocellular Carcinoma: A Pilot Study for Predicting Tumor Recurrence after Living Donor Liver Transplantation

Background/aims@#Circulating tumor cells (CTCs) with cancer stemness have been demonstrated to be a direct cause of tumor recurrence, and only few studies have reported the role of CTCs in liver transplantation (LT) for hepatocellular carcinoma (HCC). @*Methods@#Epithelial cell adhesion molecule+ (EpCAM+), cluster of differentiation 90+ (CD90+) and EpCAM+/CD90+ CTCs were sorted via fluorescence-activated cell sorting, and transcripts level of EpCAM, K19 and CD90 in the peripheral blood were analyzed via real-time polymerase chain reaction preoperatively and on postoperative days 1 and 7 in 25 patients who underwent living donor liver transplantation (LDLT) for HCC. EpCAM protein was assessed in HCC tissue using immunohistochemical staining. The median follow-up duration was 40 months. @*Results@#HCC after LDLT recurred in four out of 25 patients. Detection of EpCAM+ or CD90+ CTCs correlated well with their messenger RNA levels (p100 mAU/mL and postoperative day 1 EpCAM+/CD90+ CTCs were independent risk factors for HCC recurrence (hazard ratio, 14.64; 95% confidence interval, 1.08 to 198.20; p=0.043 and hazard ratio, 26.88; 95% confidence interval, 1.86 to 387.51; p=0.016, respectively). @*Conclusions@#EpCAM+/CD90+ CTCs can be used preoperatively and 1 day after LDLT as key biological markers in LT candidate selection and post-LDLT management.

Cognitive improvement effect of gintonin might be associated with blood-brain barrier permeability enhancement: dynamic contrastenhanced MRI pilot study

Along with the multiple neuroprotective effect, recent studies suggest that gintonin might increase the blood brain barrier permeability. We evaluated the effect of gintonin on the vascular permeability changes in different brain segments, using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). In this 8-week, randomized, open label pilot study, ten participants with subjective memory impairment but preserved cognitive function assigned to gintonin-enriched fraction (GEF) 300 mg/day or placebo groups. Korean versions of the Alzheimer's disease assessment scale (ADAS-K) and DCE-MRI parameters including Ktrans and Vp in different brain segments were evaluated at baseline and at 8 weeks after treatment. Nine participants completed the study protocol. No adverse events occurred during the observation period for 8 weeks in both groups. Following gintonin administration, increment trends of the brain permeability that did not reach a statistical significance were observed in the left hippocampus (Ktrans and Vp , both, p = 0.062), left thalamus and in left putamen (Ktrans , p = 0.062), and left insula and right amygdala (Vp , p = 0.062), but not in the control placebo group. The increment of the Ktrans value in the left thalamus from the baseline was highly correlated with the change of the ADAS scores (r = −0.900, p = 0.037). Gintonin might enhance the blood-brain barrier (BBB) permeability in the brain structures involved in cognitive functions. Further efficacy exploration for the synergistic effect of gintonin's BBB permeability enhancement to its other cognitive enhancing mechanisms are warranted.