Background and Objectives: To analyze the clinical trends and treatment patterns of thyroid cancer in the recent decade in South Korea. Materials and Methods: Two distinctive datasets, a single institutional database from 2009 to 2021 of differentiated thyroid cancer (DTC) patients (n=3145) and a nationwide database of the Korean Cancer Center Registry (KCCR) from 2005 to 2019 for patients (n=414,828) with all types of thyroid cancer, were analyzed. Annual incidence, the extent of thyroidectomy and neck dissection, T and N stages, and postoperative radioactive iodine (RAI) were investigated and descriptively presented. Results: The institutional database demonstrated that the annual cases of DTC surgeries suddenly dropped in 2014, coinciding with a social debate on overdiagnosis in South Korea. Due to changes in the staging manual and management guidelines during the study period, lobectomy has been preferred more than total thyroidectomy and the number of anterior compartment neck dissections has decreased. However, cases with lateral neck dissection and T4 stage gradually increased, suggesting that social issue did not influence the incidence of advanced thyroid diseases. The KCCR database also supported a similar phenomenon that showed a recent increase in localized and regional disease after a shock from social controversy. Conclusion Our institutional and KCCR data findings collectively indicate a steady incidence in localized and regional thyroid cancer after the initial drop triggered by the 2014 controversy in South Korea.

Background and Objectives: To analyze the clinical trends and treatment patterns of thyroid cancer in the recent decade in South Korea. Materials and Methods: Two distinctive datasets, a single institutional database from 2009 to 2021 of differentiated thyroid cancer (DTC) patients (n=3145) and a nationwide database of the Korean Cancer Center Registry (KCCR) from 2005 to 2019 for patients (n=414,828) with all types of thyroid cancer, were analyzed. Annual incidence, the extent of thyroidectomy and neck dissection, T and N stages, and postoperative radioactive iodine (RAI) were investigated and descriptively presented. Results: The institutional database demonstrated that the annual cases of DTC surgeries suddenly dropped in 2014, coinciding with a social debate on overdiagnosis in South Korea. Due to changes in the staging manual and management guidelines during the study period, lobectomy has been preferred more than total thyroidectomy and the number of anterior compartment neck dissections has decreased. However, cases with lateral neck dissection and T4 stage gradually increased, suggesting that social issue did not influence the incidence of advanced thyroid diseases. The KCCR database also supported a similar phenomenon that showed a recent increase in localized and regional disease after a shock from social controversy. Conclusion Our institutional and KCCR data findings collectively indicate a steady incidence in localized and regional thyroid cancer after the initial drop triggered by the 2014 controversy in South Korea.

Background and Objectives: To analyze the clinical trends and treatment patterns of thyroid cancer in the recent decade in South Korea. Materials and Methods: Two distinctive datasets, a single institutional database from 2009 to 2021 of differentiated thyroid cancer (DTC) patients (n=3145) and a nationwide database of the Korean Cancer Center Registry (KCCR) from 2005 to 2019 for patients (n=414,828) with all types of thyroid cancer, were analyzed. Annual incidence, the extent of thyroidectomy and neck dissection, T and N stages, and postoperative radioactive iodine (RAI) were investigated and descriptively presented. Results: The institutional database demonstrated that the annual cases of DTC surgeries suddenly dropped in 2014, coinciding with a social debate on overdiagnosis in South Korea. Due to changes in the staging manual and management guidelines during the study period, lobectomy has been preferred more than total thyroidectomy and the number of anterior compartment neck dissections has decreased. However, cases with lateral neck dissection and T4 stage gradually increased, suggesting that social issue did not influence the incidence of advanced thyroid diseases. The KCCR database also supported a similar phenomenon that showed a recent increase in localized and regional disease after a shock from social controversy. Conclusion Our institutional and KCCR data findings collectively indicate a steady incidence in localized and regional thyroid cancer after the initial drop triggered by the 2014 controversy in South Korea.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Purpose: This study aimed to investigate the oncologic outcomes and prognostic factors of salvage treatments in patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after radiotherapy (RT)-based treatment. Materials and Methods: A cancer registry was used to retrieve the records of 337 patients treated with definitive RT or concurrent chemoradiotherapy (CRT) from 2008 to 2018 at a single institution. The poor-responder group (PRG) was defined as patients with residual or recurrent disease after primary treatment, and the oncologic outcomes for each salvage treatment method were analyzed. In addition, prognostic indicators of recurrence-free survival (RFS) and overall survival (OS) were identified in patients who underwent salvage treatment. Results: After initial (C)RT, the PRG comprised 71 of the 337 patients (21.1%): 18 patients had residual disease, and 53 had recurrence after primary treatment (mean time to recurrence 19.5 months). Of these, 63 patients received salvage treatment (surgery 57.2%, re-(C)RT 23.8%, and chemotherapy 19.0%), and the salvage success rate was 47.6% at the last follow-up. The overall 2-year OS for salvage treatments was 56.4% (60.8% for the salvage surgery group and 46.2% for the salvage re-(C)RT). Salvage surgery patients with negative resection margins had better oncologic outcomes than those with close/positive resection margins. Using multivariate analyses, locoregional recurrence and residual disease after primary surgery were associated with poor outcome after salvage treatment. In Kaplan-Meier analyses, p16 status was significantly associated with OS in the initial treatment setting but not in the salvage setting. Conclusion In recurrent OPSCC after RT-based treatment, successful salvage was achieved in 56.4% patients who had undergone salvage surgery and radiation treatment. Salvage treatment methods should be selected carefully, given recurrence site as a prognostic factor for RFS.

Background/Aims: It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD).We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis. Methods: Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals.Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks. Results: A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the noninferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group. Conclusions Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.

Background and Objectives: For T1–T2 early glottic cancer, single modality treatment with radiation therapy (RT) or transoral laser microsurgery is the standard therapeutic option. However, the choice between surgery and RT has been debated for decades. Even though patient selection bias for each modality inherently exists in the retrospective study, this study aimed to compare the oncologic outcomes of the actual treatment of these patients between surgery-based treatment and RT.Materials and Method The medical records of 417 patients with T1–T2N0 glottic squamous cell carcinoma were reviewed who were treated at our institution between 1995 and 2014. The patients were divided into two groups; primarily surgery-based treatment (OP, n=209) or RT (n=208). Results: In the T1 stage, local failure, overall survival (OS), and disease-free survival (DFS) rates were not different between the OP and RT groups. However, in the T2 stage, the local failure rate was higher in the RT group (p<0.01). OS and DFS were higher in the OP group (p=0.019 and p=0.004, respectively). Larynx-preservation rate was similar in both groups (97.1% and 96.2%, p=0.576). Multivariate analysis showed that age (>65), presence of multiple primary cancer, and treatment modality were significant variables influencing OS and DFS. Conclusion Surgery-based treatment provided better local control rates, DFS, and OS in patients with T1–T2N0 glottic SCC. In the T1 stage, treatment outcomes were similar between OP and RT groups. In the T2 stage, OP showed better results than RT, suggesting that refined strategies are required to improve the oncologic outcomes of RT for T2 glottic cancer.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage and mortality.High-mobility group box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by pro-inflammatory stimuli, including viral infections, and its excessive secretion levels are related to a variety of inflammatory diseases. Here, the aim of the study was to show that SARS-CoV-2 infection induced HMGB1 secretion via active and passive release. Active HMGB1 secretion was mediated by post-translational modifications, such as acetylation, phosphorylation, and oxidation in HEK293E/ACE2-C-GFP and Calu-3 cells during SARS-CoV-2 infection. Passive release of HMGB1 has been linked to various types of cell death; however, we demonstrated for the first time that PANoptosis, which integrates other cell death pathways, including pyroptosis, apoptosis, and necroptosis, is related to passive HMGB1 release during SARS-CoV-2 infection. In addition, cytoplasmic translocation and extracellular secretion or release of HMGB1 were confirmed via immunohistochemistry and immunofluorescence in the lung tissues of humans and angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.

Background and Objectives: Airway reconstruction surgery in children is still challenging, especially in cases of combined subglottic and posterior glottic stenosis (PGS). The aim of this study was to review the underlying reasons of failure in open airway reconstruction surgeries performed for children with combined subglottic and PGS.Subjects and Method We reviewed medical records of seven children who received more than two open airway reconstruction surgeries to finally achieve and maintain decannulation status for more than one year. Twenty-two reconstructive surgeries were performed and they consisted of 19 laryngotracheal reconstruction (LTR), 2 cricotracheal resection with end-toend anastomosis (CTR) and one extended CTR. For each patient, the following potential causes of failure were evaluated; preoperative evaluation (PE), type of reconstruction (TR), single vs. double staging (SDS), type of stent (TS), and perioperative optimization (PO). Results: The median age of patients at the time of surgery was 32 months (range, 4-64 months). Successful decannulation was achieved after the median open surgery of three (range, 2-5 times for each patient). Recognized causes of failure were as follows: 8 insufficient PE, 10 inadequate TR, 3 improper SDS, 8 ill-chosen TS, and 2 inappropriate PO. Conclusion PE of dynamic airway is important, especially vocal fold mobility and tracheomalacia. Types of reconstruction should be carefully decided after full consideration of potential causes of failure, and adequate laryngotracheal stent is essential.