Search

The consequences of coronavirus disease 2019 (COVID-19) are particularly severe in older adults with a disproportionate number of severe and fatal outcomes. Therefore, this integrative review aimed to provide a comprehensive overview of the clinical characteristics, management approaches, and prognosis of older patients diagnosed with COVID-19. Common clinical presentations in older patients include fever, cough, and dyspnea. Additionally, preexisting comorbidities, especially diabetes and pulmonary and cardiovascular diseases, were frequently observed and associated with adverse outcomes. Management strategies varied, however, early diagnosis, vigilant monitoring, and multidisciplinary care were identified as key factors for enhancing patient outcomes. Nonetheless, the prognosis remains guarded for older patients, with increased rates of hospitalization, mechanical ventilation, and mortality. However, timely therapeutic interventions, especially antiviral and supportive treatments, have demonstrated some efficacy in mitigating the severe consequences in this age group. In conclusion, while older adults remain highly susceptible to severe outcomes from COVID-19, early intervention, rigorous monitoring, and comprehensive care can play a pivotal role in improving their clinical outcomes.

Abstract Purpose There is a lack of real‐world data in Asian populations for brigatinib, a next‐generation anaplastic lymphoma kinase (ALK) inhibitor for patients with non‐small cell lung cancer (NSCLC). This study analysed real‐world outcomes and dosing patterns for brigatinib in patients with crizotinib‐refractory ALK+ NSCLC in South Korea. Methods This retrospective, non‐interventional, cohort study used South Korean Health Insurance and Review Assessment claims data for adults with ALK+ NSCLC who initiated brigatinib between 19 April 2019 and 31 March 2021 after receiving prior crizotinib. Patients' characteristics, time to discontinuation (TTD), time to dose reduction, overall survival (OS) and treatment adherence were assessed. Results The study included 174 patients (56.9% male; 27.0% with a history of brain metastases). Median duration of prior crizotinib was 17 (range 0.3–48) months. Median follow‐up after brigatinib initiation was 18 (range 0–34) months. Overall, 88.5% of patients received full‐dose brigatinib (180 mg/day) and 93.1% of patients were adherent (proportion of days covered ≥0.8). The median TTD was 24.9 months (95% CI 15.2–not reached). The probability of continuing treatment was 63.2% at 1 year and 51.5% at 2 years. The probability of continuing at full or peak dose was 79.7% at 1 year and 75.6% at 2 years. Median OS was not reached. The 2‐year OS rate was 68.7%. Conclusions In this first nationwide retrospective study using national insurance claim data, brigatinib demonstrated real‐world clinical benefit as second‐line treatment after prior crizotinib in ALK+ NSCLC patients in South Korea.

Abstract Background In the intensive care unit (ICU), we may encounter patients who have completed a Do-Not-Resuscitate (DNR) or a Physician Orders to Stop Life-Sustaining Treatment (POLST) document. However, the characteristics of ICU patients who choose DNR/POLST are not well understood. Methods We retrospectively analyzed the electronic medical records of 577 patients admitted to a medical ICU from October 2019 to November 2020, focusing on the characteristics of patients according to whether they completed DNR/POLST documents. Patients were categorized into DNR/POLST group and no DNR/POLST group according to whether they completed DNR/POLST documents, and logistic regression analysis was used to evaluate factors influencing DNR/POLST document completion. Results A total of 577 patients were admitted to the ICU. Of these, 211 patients (36.6%) had DNR or POLST records. DNR and/or POLST were completed prior to ICU admission in 48 (22.7%) patients. The DNR/POLST group was older (72.9 ± 13.5 vs. 67.6 ± 13.8 years, p

Abstract Background About 3%–5% of non‐small cell lung cancer (NSCLC) presents positive anaplastic lymphoma kinase (ALK). Recently, several target agents have been approved as a treatment for ALK‐positive NSCLC. This study aimed to analyze the real‐world efficacy and outcome when administered crizotinib, the first approved target agent for ALK‐positive NSCLC, according to first‐ or late‐line treatment. Methods A total of 290 patients with ALK‐positive advanced NSCLC who were treated with crizotinib in 15 institutions in South Korea from January 2009 to December 2018 were enrolled. Results The median age of patients was 57.0 years, and 50.3% were male. The median follow‐up duration was 29.3 months. Among them, 113 patients received crizotinib as first‐line therapy. The objective response rate (ORR) was 60.1% (57.0% for first‐line recipients, 61.8% for second−/later‐line). Median (95% CI) progression‐free survival (PFS) was 13.7 (11.6–17.0) months. For first‐line recipients, overall survival (OS) was 26.3 (17.6–35.0) months. No significant difference in ORR, PFS and OS, according to the setting of crizotinib initiation, was observed. In a multivariate Cox regression analysis, old age, male gender, initially metastatic, and number of metastatic organs were associated with poor PFS and OS. The most common adverse events were nausea and vomiting, and severe adverse event leading to dose adjustment was hepatotoxicity. Conclusions ORR, PFS, OS, and adverse event profiles were comparable to previous clinical trials. Our findings could aid in the efficient management of ALK‐positive lung cancer patients.

Abstract Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive subtype of non‐small cell lung cancer with a poor prognosis. Spontaneous regression, that is, partial or complete disappearance of a malignancy without medical intervention, is extremely rare in LCNEC. Herein, we present a case of spontaneous complete regression in a 71‐year‐old male patient with recurrent LCNEC after surgical resection. The patient was diagnosed with stage IB LCNEC and underwent surgical resection. At 1‐year follow‐up, chest computed tomography revealed a recurrent lesion next to the stump site and enlargement of lymph nodes 4R and 7; recurrent LCNEC was confirmed. The patient declined chemoradiation therapy. One year after recurrence, the patient experienced severe multifocal necrotizing pneumonia and was treated with antibiotics, resulting in a gradual decrease in the size of the recurrent lesion. Five years after the initial diagnosis, positron emission tomography/computed tomography revealed no hypermetabolic lesions, indicating the spontaneous complete regression of LCNEC.

Abstract There is an unmet need for biomarkers for the diagnosis of lung cancer and decision criteria for lung biopsy. We comparatively investigated the lung microbiomes of patients with lung cancer and benign lung diseases. Patients who underwent bronchoscopy at Chungnam National University Hospital between June 2021 and June 2022 were enrolled. Bronchoalveolar lavage fluid (BALF) was collected from 24 patients each with lung cancer and benign lung diseases. The samples were analyzed using 16S rRNA-based metagenomic sequencing. We found that alpha diversity and the beta diversity distribution (P = 0.001) differed significantly between patients with benign lung diseases and those with lung cancer. Firmicutes was the most abundant phylum in patients with lung cancer (33.39% ± 17.439), whereas Bacteroidota was the most abundant phylum in patients with benign lung disease (31.132% ± 22.505), respectively. In differential abundance analysis, the most differentially abundant microbiota taxon was unclassified_SAR202_clade, belonging to the phylum Chloroflexi. The established prediction model distinguished patients with benign lung disease from those with lung cancer with a high accuracy (micro area under the curve [AUC] = 0.98 and macro AUC = 0.99). The BALF microbiome may be a novel biomarker for the detection of lung cancer.

Purpose Previous studies have reported that presarcopenia negatively affects rectal cancer treatment. However, most studies have analyzed patients including majority of open surgery, and the association between presarcopenia and clinical outcomes after laparoscopic rectal cancer surgery remains unclear. This study aimed to evaluate the impact of presarcopenia on the clinical and oncological outcomes after laparoscopic rectal cancer surgery. Methods Three hundred and one patients undergoing laparoscopic rectal cancer surgery between December 2009 and May 2016 were enrolled. Body composition was assessed using computed tomography by measuring the muscle and fat areas at the third lumbar (L3) vertebra. The L3 skeletal muscle area was used to calculate the skeletal muscle index and evaluate presarcopenia. Results Presarcopenia was more common in older (≥70 years, P=0.008) or female patients (P=0.045). Patients with presarcopenia had decreased skeletal muscle area (P

Abstract Immunosenescence and exhaustion are involved in the development and progression of type 2 diabetes (T2D) and metabolic liver diseases, including fatty liver, fibrosis, and cirrhosis, in humans. However, the relationships of the senescence and exhaustion of T cells with insulin resistance-associated liver diseases remain incompletely understood. To better define the relationship of T2D with nonalcoholic fatty liver disease, 59 patients (mean age 58.7 ± 11.0 years; 47.5% male) with T2D were studied. To characterize their systemic immunophenotypes, peripheral blood mononuclear cells were analyzed using flow cytometry. Magnetic resonance imaging (MRI)-based proton density fat fraction and MRI-based elastography were performed using an open-bore, vertical-field 3.0 T scanner to quantify liver fat and fibrosis, respectively. The participants with insulin resistance had a significantly larger population of CD28 − CD57+ senescent T cells among the CD4+ and CD8 + T cells than those with lower Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) values. The abundances of senescent CD4+ and CD8 + T cells and the HOMA-IR positively correlated with the severity of liver fibrosis, assessed using MRI-based elastography. Interleukin 15 from hepatic monocytes was found to be an inducer of bystander activation of T cells, which is associated with progression of liver disease in the participants with T2D. Furthermore, high expression of genes related to senescence and exhaustion was identified in CD4+ and CD8 + T cells from the participants with nonalcoholic steatohepatitis or liver cirrhosis. Finally, we have also demonstrated that hepatic T-cell senescence and exhaustion are induced in a diet or chemical-induced mouse model with nonalcoholic steatohepatitis. In conclusion, we have shown that T-cell senescence is associated with insulin resistance and metabolic liver disease in patients with T2D.

Background Remote ischemic postconditioning (RIPoC) is induced by several cycles of brief, reversible, mechanical blood flow occlusion, and reperfusion of the distal organs thereby protecting target organs. We investigated if RIPoC ameliorated liver injury in a lipopolysaccharide (LPS)-induced endotoxemic rats. Methods Protocol 1) Rats were administered LPS and samples collected at 0, 2, 6, 12, and 18 h. 2) After RIPoC at 2, 6, and 12 h (L+2R+18H, L+6R+18H, and L+12R+18H), samples were analyzed at 18 h. 3) RIPoC was performed at 2 h, analysis samples at 6, 12, 18 h (L+2R+6H, L+2R+12H, L+2R+18H), and RIPoC at 6 h, analysis at 12 h (L+6R+12H). 4) Rats were assigned to a control group while in the RIPoC group, RIPoC was performed at 2, 6, 10, and 14 h, with samples analyzed at 18 h. Results Protocol 1) Liver enzyme, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB) levels increased while superoxide dismutase (SOD) levels decreased over time. 2) Liver enzyme and MDA levels were lower while SOD levels were higher in L+12R+18H and L+6R+18H groups when compared with L+2R+18H group. 3) Liver enzyme and MDA levels were lower while SOD levels were higher in L+2R+6H and L+6R+12H groups when compared with L+2R+12H and L+2R+18H groups. 4) Liver enzyme, MDA, TNF-α, and NF-κB levels were lower while SOD levels were higher in RIPoC group when compared with control group. Conclusions RIPoC attenuated liver injury in the LPS-induced sepsis model by modifying inflammatory and oxidative stress response for a limited period.

Abstract Background: The rationale for the present study is a result of the COVID-19 pandemic, as there are fewer opportunities available for older adults to engage in face-to-face interaction and social activities, which may result in changes in the communication methods with their social contacts. The purpose of this study was to explore the relationship between methods of social connectedness and emotional well-being outcomes among older adults at the start of the pandemic. Methods: Two thousand five hundred and fifty-eight older adults Medicare beneficiaries (65 + years of age) in the National Health and Aging Trends Study at wave 10 (June 2020 to January 2021) were selected for cross-sectional analysis. Participants were measured on brief questionnaires regarding forms of communication with family and friends before and during the pandemic. Emotional well-being outcomes were measured on single items of sadness/depressed and loneliness; as well as a 6-item Likert scale of anxiety during the pandemic. Paired sample t-tests were utilized to examine the forms of communication between before and during pandemic. Hierarchical regressions were conducted to assess the relationship between forms of communication and emotional well-being outcomes. Results: We found that there were overall decreases in communication frequency during pandemic. Findings from regression analyses indicated information communication technology (ICT) are associated with negative emotional well-being outcomes, whereas in-person social contact are associated with lower levels of negative affect. Conclusion: These findings suggest utilizing higher levels of ICT has negative implications for older adults’ emotional well-being, contrasting with the positive implication of in-person contacts. These findings highlight the role of ICT in emotional well-being among older adults during pandemic.

Abstract Background/Aims Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Ultrasound, the most used tool for diagnosing NAFLD, is operator-dependent and shows suboptimal performance in patients with mild steatosis. However, few studies have been conducted on whether alternative noninvasive methods are useful for diagnosing mild hepatic steatosis. Also, little is known about whether noninvasive tests are useful for grading the severity of hepatic steatosis or the degree of intrahepatic inflammation. Therefore, we aimed to evaluate whether the HSI, the FLI and HU values in CT could be used to discriminate mild hepatic steatosis and to evaluate the severity of hepatic steatosis or the degree of intrahepatic inflammation in patients with low-grade fatty liver disease using liver biopsy as a reference standard. Methods Demographic, laboratory, CT imaging, and histological data of patients who underwent liver resection or biopsy were analyzed. The performance of the HSI, HU values and the FLI for diagnosing mild hepatic steatosis was evaluated by calculating the area under the receiver operating characteristic curve. Whether the degree of hepatic steatosis and intrahepatic inflammation could be predicted using the HSI, HU values or the FLI was also analyzed. Moreover, we validate the results using magnetic resonance imaging proton density fat fraction as an another reference standard. Results The AUROC for diagnosing mild hepatic steatosis was 0.810 (p

We aimed to assess the temporal trends of incident syphilis and its associated risk factors among men with HIV (Human Immunodeficiency Virus) in Korea during the COVID-19 pandemic. We conducted a retrospective cohort study of men with HIV attending an HIV clinic in Korea between 2005 and 2022. Of 767 men with HIV, 499 were included and contributed 3220 person-years (PY) of the observation period. Eighty-two patients were diagnosed with incident syphilis, with an overall incidence of 2.55/100 PY (95% confidence interval [CI] 20.56–31.53). The incidence of syphilis per 100 PY gradually decreased from 2.43 (0.79–7.42) in 2005–2007 to 1.85 (1.08–3.17) in 2014–2016; however, it increased to 3.0 (1.99–4.53) in 2017–2019, and further to 3.33 (2.26–4.89) in 2020–2022. A multivariate analysis identified young age (≤30 years versus >50, adjusted HR 6.27, 95% CI 2.38–16.56, p < 0.001), treponemal test positive at baseline (2.33, 1.48–3.67, p < 0.001), men who have sex with men (2.36, 1.34–4.16, p = 0.003), and history of incarceration (2.62, 1.21–5.67, p = 0.015) as risk factors for incident syphilis. Recently, syphilis incidence in men with HIV has increased in Korea, especially in young patients and at-risk groups, highlighting the need for enhanced regular screening and targeted behavioral interventions among these populations.

Recognizing how human activities affect hydrological systems is vital for the sustainable preservation and effective management of water resources in the watershed. Hence, this paper focuses on the hydrological response to land use and land cover (LULC) change scenarios in the Anyang watershed, South Korea. We obtained LULC data maps for the years 2000, 2013, and 2022 from the local government, revealing significant changes over the years. Agricultural lands experienced a 6.2% increase from 2000 to 2022, and pastureland expanded by 8.67% over two decades. The SWAT model was utilized to assess the impact of LULC on the hydrological components of the study watershed. Model calibration and validation for each LULC change were carried out using the SWAT-CUP program, considering the recorded streamflow information of the region. An excellent agreement was reached between the simulated and measured streamflow in both the calibration and validation stages under various LULC conditions. The Nash–Sutcliffe model efficiency (NSE), the objective function, demonstrated values of 0.9, 0.89, and 0.89 during the calibration for 2000, 2013, and 2022, respectively, in the LULC scenario, while for the validation, we obtained values of 0.82, 0.78, and 0.80 for 2000, 2013, and 2022, respectively. Our findings indicate that the surface runoff rise contributed much to the water yield increase over the two decades compared to the other components in terms of the water yield, while the contribution of evapotranspiration (ET) to the watershed hydrological cycle declined by 1.66% from 2000 to 2022. The southeastern sub-basin part showed a high groundwater recharge distribution due to agricultural land, rice area, and forest area changes.

Real-world data on the use and outcomes of crizotinib in ROS1-rearranged non-small-cell lung cancer (NSCLC) are limited. This study aims to analyze the real-world efficacy of crizotinib in South Korea and explore the utilization of liquid biopsies that implement next-generation sequencing (NGS) using cell-free total nucleic acids. In this prospective multicenter cohort study, 40 patients with ROS1-rearranged NSCLC, either starting or already on crizotinib, were enrolled. Patients had a median age of 61 years, with 32.5% presenting brain/central nervous system (CNS) metastases at treatment initiation. At the data cutoff, 48.0% were still in treatment; four continued with it even after disease progression due to the clinical benefits. The objective response rate was 70.0%, with a median duration of response of 27.8 months. The median progression-free survival was 24.1 months, while the median overall survival was not reached. Adverse events occurred in 90.0% of patients, primarily with elevated transaminases, yet these were mostly manageable. The NGS assay detected a CD74–ROS1 fusion in 2 of the 14 patients at treatment initiation and identified emerging mutations, such as ROS1 G2032R, ROS1 D2033N, and KRAS G12D, during disease progression. These findings confirm crizotinib’s sustained clinical efficacy and safety in a real-world context, which was characterized by a higher elderly population and higher rates of brain/CNS metastases. The study highlights the clinical relevance of liquid biopsy for detecting resistance mechanisms, suggesting its value in personalized treatment strategies.

The extracellular matrix (ECM) exerts physiological activity, facilitates cell-to-cell communication, promotes cell proliferation and metastasis, and provides mechanical support for tumor cells. The development of solid tumors is often associated with increased stiffness. A stiff ECM promotes mechanotransduction, and the predominant transcription factors implicated in this phenomenon are YAP/TAZ, β-catenin, and NF-κB. In this study, we aimed to investigate whether YAP is a critical mediator linking matrix stiffness and PD-L1 in lung adenocarcinoma. We confirmed that YAP, PD-L1, and Ki-67, a marker of cell proliferation, increase as the matrix stiffness increases in vitro using the lung adenocarcinoma cell lines PC9 and HCC827 cells. The knockdown of YAP decreased the expression of PD-L1 and Ki-67, and conversely, the overexpression of YAP increased the expression of PD-L1 and K-67 in a stiff-matrix environment (20.0 kPa). Additionally, lung cancer cells were cultured in a 3D environment, which provides a more physiologically relevant setting, and compared to the results obtained from 2D culture. Similar to the findings in 2D culture, it was confirmed that YAP influenced the expression of PD-L1 and K-67 in the 3D culture experiment. Our results suggest that matrix stiffness controls PD-L1 expression via YAP activation, ultimately contributing to cell proliferation.

Abstract Introduction The PACIFIC study demonstrated that durvalumab consolidation therapy significantly improved progression‐free survival (PFS) and overall survival (OS) in patients with unresectable stage III non‐small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT). However, there was no clinical benefit in both PFS and OS in epidermal growth factor receptor (EGFR) mutation‐positive patient groups in a post hoc exploratory analysis. Moreover, the clinical effects of immune checkpoint inhibitors (ICIs) in EGFR mutation‐positive stage IV NSCLC were demonstrated to be poor. Personalized treatment according to the mutation status is also required in stage III NSCLC. Lazertinib, a third‐generation EGFR tyrosine kinase inhibitor (TKI), is newly developed and approved for use in Korea. Methods This prospective, open, single‐arm, multicenter, phase II clinical trial aims to evaluate the efficacy and safety of lazertinib as a consolidative therapy after CCRT treatment in unresectable, EGFR mutation‐positive NSCLC stage III patients. The primary endpoint of this study is PFS, and the secondary endpoints are OS, objective response rate (ORR), duration of response (DoR), time to death or distant metastasis (TTDM), and safety profiles. Discussion Our study may extend the indications for third‐generation EGFR‐TKIs to treat patients with stage III NSCLC. Moreover, using this drug to treat stage III NSCLC would emphasize the value of mutation analysis and personalized medicine.

Leydig cell tumors can cause precocious puberty in prepubertal males. Radical orchiectomy is the standard therapy for Leydig cell tumors, with a good overall prognosis. Here, we present a rare case of secondary central precocious puberty caused by a Leydig cell tumor in a 5 year-old boy. He had an isosexual precocity and advanced bone age. Laboratory investigations showed high testosterone and low gonadotropin levels, presenting as precocious pseudo-puberty. Seven months after surgical removal of the tumor, the patient was diagnosed with central precocious puberty by GnRH stimulation test. He was initiated on GnRH agonist therapy, which has been administered every 13 weeks to date. Post-surgery surveillance of Leydig cell tumors should include evaluation for progression to secondary central precocious puberty as well as recurrence of Leydig cell tumor or metachronous tumors in prepubertal children.

We report a case of pulmonary paragonimiasis diagnosed by transbronchial lung cryobiopsy (TBLC). TBLC is likely to be a superior method to transbronchial forceps biopsy because TBLC can get larger specimens, resulting in a higher chance of containing the eggs. A male patient aged 57 years presented with hemoptysis and dyspnea on exertion. His initial chest computed tomography scans showed a cavitary nodule with a peripheral ground-glass appearance, leading to a prescription of an oral antibiotic, with an initial assumption of pneumonia. A follow-up chest computed tomography, however, revealed an appearance of a new nodule adjacent to the original nodule. TBLC and transbronchial forceps biopsy were done to rule out lung cancer and eventually, the eggs of Paragonimus westermani were found using TBLC. Praziquantel was prescribed, showing improvements in symptoms and chest X-ray findings. TBLC has more potential to be utilized as a diagnostic method than transbronchial forceps biopsy because it has a better chance to confirm pulmonary paragonimiasis, which can be initially suspected as pulmonary tuberculosis or lung cancer.

Abstract Background The use of immune checkpoint inhibitors (ICIs) as first‐line treatment rather than as second‐line treatment makes a big difference in the drug efficacy and progression‐free survival. However, the mechanism for this is still not clear. This study aimed to analyze the effects of the rest period between chemotherapy and immunotherapy on the efficacy of ICIs. Methods This study included 100 patients with advanced NSCLC treated with PD‐1/PD‐L1 inhibitors at Chungnam National University Hospital (CNUH) between May 2016 and August 2019. The rest period was defined from the last dose of cytotoxic chemotherapy to the first dose of ICIs. We retrospectively reviewed patients' clinical data and blood test records and analyzed lymphocyte subsets using flow cytometry. Results The median rest period was 64 days. The long rest period group (≥36 days) showed significantly higher clinical benefits than the short rest period group (

Abstract Cancers are the leading cause of death among people living with HIV/AIDS (PLWHA); however, nationwide studies on cancer incidence are limited. We aimed to determine the trends in the incidence rates of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) among Korean PLWHA. Data from the National Health Insurance Sharing Service from 2004 to 2017 were collected. Age- and sex-adjusted standardized incidence ratios (SIRs) for various cancer types relative to the general population were calculated. Of the 11,737 PLWHA followed-up for 65,052 person-years (PYs), 445 (ADCs, 130 and NADCs, 298) developed cancer. The incidence rate of ADCs decreased, whereas that of NADCs remained unchanged. PLWHA were at an increased risk of ADCs (SIR: 12.6, 95% CI: 10.6–15.0), including Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical cancer, and some NADCs, including anal cancer, lung cancer, liver cancer, and oropharyngeal cancer. Of the 396 patients who received antiretroviral therapy (ART), 215 with optimal adherence had lower incidence rates for ADCs and NADCs than those with non-optimal adherence. The 5-year survival rate of PLWHA with NADCs was 57.8%. Close surveillance and routine screening of cancers and improvement in ART adherence are required to improve the clinical outcomes of PLWHA.

Purpose To evaluate the feasibility of pediatric low-dose facial CT reconstructed with filtered back projection (FBP) using adequate kernels. Materials and Methods We retrospectively reviewed the clinical and imaging data of children aged < 10 years who underwent facial CT at our emergency department. The patients were divided into two groups: low-dose CT (LDCT; Group A, n = 73) with a fixed 80-kVp tube potential and automatic tube current modulation (ATCM) and standard-dose CT (SDCT; Group B, n = 40) with a fixed 120-kVp tube potential and ATCM. All images were reconstructed with FBP using bone and soft tissue kernels in Group A and only bone kernel in Group B. The groups were compared in terms of image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Two radiologists subjectively scored the overall image quality of bony and soft tissue structures. The CT dose index volume and dose-length product were recorded. Results Image noise was higher in Group A than in Group B in bone kernel images (p < 0.001). Group A using a soft tissue kernel showed the highest SNR and CNR for all soft tissue structures (all p < 0.001). In the qualitative analysis of bony structures, Group A scores were found to be similar to or higher than Group B scores on comparing bone kernel images. In the qualitative analysis of soft tissue structures, there was no significant difference between Group A using a soft tissue kernel and Group B using a bone kernel with a soft tissue window setting (p > 0.05). Group A showed a 76.9% reduction in radiation dose compared to Group B (3.2 ± 0.2 mGy vs. 13.9 ± 1.5 mGy; p < 0.001). Conclusion The addition of a soft tissue kernel image to conventional CT reconstructed with FBP enables the use of pediatric low-dose facial CT protocol while maintaining image quality.

Abstract Objectives Delayed pneumothorax can cause an emergency room visit and be life‐threatening in case of tension pneumothorax after transthoracic needle biopsy. We hypothesized that most delayed pneumothoraces are diagnosed by later enlargement of occult pneumothorax due to the low diagnostic accuracy of a chest X‐ray. Lung ultrasound is a highly accurate tool for detection of pneumothorax. The aim of this study is to evaluate the diagnostic accuracy of lung ultrasound for prediction of delayed pneumothorax on chest X‐ray. Methods This prospective pilot study was performed between April 2020 and July 2020 in Chungnam National University Hospital. The participants underwent chest X‐rays and lung ultrasound before, immediately after, and 3 h after transthoracic needle biopsy, respectively. The presence or absence of lung sliding at each anterior BLUE‐point on an ultrasound and pneumothorax on a chest X‐ray was recorded. Results Pneumothorax occurred in 17 (35.4%) participants, and three of them underwent chest tube replacement. Of the 17 (35.4%) cases of pneumothorax, five participants (10.4%) were diagnosed with delayed pneumothorax. Three out of five participants showed loss of lung sliding on lung ultrasound before the diagnosis of delayed pneumothorax. Therefore, the sensitivity of lung sliding on lung ultrasound for early detection of delayed pneumothorax was 60%. Two undetected cases were asymptomatic, and the pneumothoraces were exceedingly small and recovered spontaneously. Thus, sensitivity for detection of clinically meaningful delayed pneumothorax requiring chest tube replacement was 100% (2/2). Conclusion Lung ultrasound can probably predict clinically meaningful delayed pneumothorax after transthoracic needle lung biopsy.

Purpose To investigate growth response in children with either idiopathic short stature (ISS) or growth hormone (GH) deficiency (GHD). Methods The data of prepubertal GHD or ISS children treated using recombinant human GH were obtained from the LG Growth Study database. GHD children were further divided into partial and complete GHD groups. Growth response and factors predicting growth response after 1 and 2 years of GH treatment were investigated. Results This study included 692 children (98 with ISS, 443 partial GHD, and 151 complete GHD). After 1 year, changes in height standard deviation score (ΔHt-SDS) were 0.78, 0.83, and 0.96 in ISS, partial GHD, and complete GHD, respectively. Height velocity (HV) was 8.72, 9.04, and 9.52 cm/yr in ISS, partial GHD, and complete GHD, respectively. ΔHt-SDS and HV did not differ among the 3 groups. Higher initial body mass index standard deviation score (BMI-SDS) and midparental height standard deviation score (MPH-SDS) were predictors for better growth response after 1 year in ISS and the partial GHD group, respectively. In the complete GHD group, higher Ht-SDS and BMI-SDS predicted better growth response after 1 year. After 2 years of GH treatment, higher BMI-SDS and MPH-SDS predicted a better growth outcome in the partial GHD group, and higher MPH-SDS was a predictor of good growth response in complete GHD. Conclusions Clinical characteristics and growth response did not differ among groups. Predictors of growth response differed among the 3 groups, and even in the same group, a higher GH dose would be required when poor response is predicted.

Abstract Background Studies on the application of targeted therapies for patients with non‐small cell lung cancer (NSCLC) who harbor rare genetic mutations are ongoing. In the present study, we investigated the real‐world data of NSCLC patients who harbor rare mutations. Methods We retrospectively analyzed patients with advanced or metastatic nonsquamous NSCLC aged >20 years with confirmed rare mutations (BRAF, ROS1, MET, RET, HER2, FGFR, and NTRK) from January 2015 to September 2020 at nine tertiary hospitals. In addition, we validated the lung cancer PCR panel kit in patients with confirmed mutations by NGS. Results Among 118 patients included, 88 received platinum‐based chemotherapy as first‐line chemotherapy. The progression‐free survival of patients with BRAF, ERBB2, MET, RET, and ROS1 mutations was 10.9 months (95% confidence interval [CI]: 1.3–20.5), 5.3 months (95% CI: 3.0–7.5), 7.2 months (95% CI: 3.6–10.9), 11.4 months (95% CI: 9.2–13.6), and 10.0 months (95% CI: 3.7–16.4) respectively (p = 0.041). The median overall survival (OS) was not reached in patients with ROS1 mutations; however, in BRAF, ERBB2, MET, and RET mutant patients, median OS was 14.1 months (95% CI: 10.1–14.1), 34.5 months (95% CI: 13.2–36.9), 22.7 months (95% CI: 1.7–24.0), and 29.8 months (95% CI: 28.9–61.3), respectively (p = 0.006). Of the 27 tissue samples, 26 (96.3%) showed the same PCR panel kit result with NGS. Conclusions First‐line platinum‐based chemotherapy showed durable benefit in patients with advanced or metastatic nonsquamous NSCLC harboring rare genetic mutation other than EGFR or ALK.

Abstract Background The utilization of a rapid response team (RRT) has influenced the clinical outcomes of patients in the general ward. However, the characteristics of RRT-screened patients who are transferred to the intensive care unit (ICU) are unknown. Therefore, the present study aimed to evaluate these factors. Methods We conducted a retrospective study using patient data from a tertiary medical center in Republic of Korea between January 2016 and December 2017. Multivariate logistic regression analyses were performed to assess the factors associated with the risk of in-hospital mortality. Results A total of 1,096 patients were included: 389 patients were transferred to the ICU, and 707 patients stayed in the ward. Patients in the ICU group were more likely to be admitted for medical reasons, hepatobiliary disease, and high heart rate. More interventions were performed, hospital stays were longer, and the 28-day and in-hospital mortality rates were higher in the ICU group than in the ward group. Multivariate logistic regression analyses showed that risk factors affecting ICU admission were higher Sequential Organ Failure Assessment (SOFA) score, National Early Warning Score (NEWS), platelet count, and lactate level. ICU transfer was not associated with in-hospital mortality. Conclusions Among RRT-screened patients, those with higher SOFA score, NEWS, and lactate level were more likely to be transferred to the ICU. Therefore, these patients should be closely monitored and considered for ICU transfer.

Purpose To assess the prevalence of incidentally detected lumbar spondylolysis in children. Materials and Methods We retrospectively reviewed the data of 809 patients under the age of 11 years (mean age, 7.0 ± 2.7 years; boys:girls = 479:330) who underwent abdominal and pelvic CT between March 2014 and December 2018. We recorded the presence, level, and laterality (unilateral or bilateral) of spondylolysis. Patients were divided into two groups based on the presence of spondylolysis: the spondylolysis (SP) and non-SP groups. Results In total, 21 cases of spondylolysis were detected in 20 patients (20/809, 2.5%). The mean age of the SP group was higher than that of the non-SP group (7.8 ± 1.8 vs. 6.9 ± 2.7 years, p > 0.05). The prevalence of spondylolysis in boys was higher than that in girls (15/479 [3.1%] vs. 5/330 [1.5%], p > 0.05). The prevalence of spondylolysis in school-age children (6–10 year olds) was higher than that in preschool-age children (0–5 year olds) (17/538 [3.2%] vs. 3/271 [1.1%], p > 0.05). L5 was the most common level of spondylolysis (76.2%); one 8-year-old boy had twolevel spondylolysis. One case of isthmic spondylolisthesis was detected in a 10-year-old boy (1/809, 0.1%). There were 11 unilateral spondylolysis cases (11/21, 52.4%). Conclusion In our study, the prevalence of spondylolysis in children under the age of 11 was 2.5%. The prevalence was higher in boys than in girls and in school-age than in preschool-age children, despite the lack of any statistically significant differences.

This study examines the long-term climate predictability in the Seomjin River basin using statistical methods, and explores the effects of incorporating the duration of climate indices as predictors. A multiple linear regression model is employed, utilizing 44 climate indices as predictors, including global climate patterns and local meteorological factors specific to the area. The analysis focuses on teleconnections between the target variables and climate indices, considering the value of each index, not only for the corresponding month, but also for an average value over a duration of 2 and 3 months. The correlation analysis reveals that considering the duration of climate indices allows for the inclusion of predictors with higher correlation, leading to improved forecasting accuracy. The goodness of fit analysis, which compares predicted mean values with observed values on a monthly basis, indicates that neither precipitation nor temperature is significantly affected by the duration. However, the tercile hit rate analysis, comparing the results with historical data, shows a 34.7% hit rate for precipitation, both before and after, reflecting the duration of indices. Notably, for long lead times (10–12 months), the hit rate improves after incorporating the duration. In contrast, for temperature, the tercile hit rate is higher before considering the duration. Nonetheless, both precipitation and temperature exhibit hit rates higher than the baseline probability of 33.3%, affirming the reliability of long-term forecasts in the Seomjin River basin. Incorporating the duration of climate indices enhances the selection of predictors with higher correlation, resulting in a notable impact on long-lead precipitation forecasting. However, since temperature demonstrates little irregularity and displays a consistent pattern according to the month and season, the effect of considering the duration is relatively insignificant compared to precipitation. Future research will explore the decrease in hit rate due to reflecting the duration in temperature by extending the analysis to other regions.

One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.

Morning glory syndrome (MGS) is a rare congenital optic disc anomaly with a characteristic fundal finding with severe visual impairment. It may occur in association with various systemic manifestations, even though most of the reported cases were isolated. A 6-year-old male visited the nephrology clinic with a history of microscopic hematuria and at the age of 12 years, he was diagnosed thin glomerular basement membrane nephropathy by kidney biopsy. After the following years, the patient had progressive deterioration of visual acuity, and diagnosed as MGS. Whole Exome Sequencing of this patient and his mother revealed heterozygous COL4A4 mutations [c.81_86del (p.Ile29_Leu30del)]. It is more reasonable to consider MGS seen in this patient as a coincidental finding of autosomal dominant Alport syndrome. To our knowledge, this case represents the first case report of autosomal dominant Alport syndrome associated with MGS.

Despite potential health care needs, many older adults do not make concrete plans about future care in late life. Prior community programs have not addressed this need via Cooperative Extension systems. To address these gaps, we developed and evaluated the pilot study program, Future Care Planning, designed to help older adults plan for their own personal, health, and environmental care. The Plan Ahead program (Plan Ahead) consists of two sessions implemented over two weeks to teach older adults to plan for their future care across multiple domains, including health communication, aging in place, and end-of-life discussion. Iowa State University Human Science Extension and Outreach specialists delivered the program to a sample of 161 community-residing older adults. We evaluated 1) the feasibility of the Plan Ahead program, 2) the acceptability of the program, and 3) participants’ intention to change their future care planning. Participants reported that the program was useful and relatively easy to implement. They also reported being satisfied with the content and willing to attend other relevant programs in the future. Overall, the findings suggest that Plan Ahead is feasible as an educational program to help older adults prepare for future care planning.

Hereditary spherocytosis is the most common hereditary red blood cell membrane disorder. It results from a deficiency in certain proteins that are part of the red blood cell membrane cytoskeleton. We report a case of adrenal myelolipoma in a 23-year-old patient with hereditary spherocytosis. She was diagnosed with hereditary spherocytosis at 7 months of age. As she grew older, hemoglobin level was low, so splenectomy was recommended, but continuous follow up was not possible due to the circumstances of the patient, so the splenectomy was delayed. Adrenal myelolipoma was discovered incidentally at the age of 23 with abdominal pain and cholecystitis with gallstones at the time. Myelolipoma is a benign tumor of the mesenchymal origin; its etiology remains unclear. Myelolipoma is composed of adipose and hematopoietic tissues and mainly arises from adrenal tissues. The mass is often detected during routine radiologic examinations because myelolipoma is usually asymptomatic and not generally associated with hematologic diseases. The prevalence of myelolipoma appears to be increasing due to the increased use of imaging modalities. The association of myelolipoma with hereditary spherocytosis has rarely been reported in the literature. To our best knowledge, this is the first report of adrenal myelolipoma associated with hereditary spherocytosis in the Korean population.

Background The diagnosis and prediction of prognosis are important in patients with sepsis, and presepsin is helpful. In this study, we aimed to examine the usefulness of presepsin in predicting the prognosis of sepsis in Korea. Methods Patients diagnosed with sepsis according to the sepsis-3 criteria were recruited into the study and classified into surviving and non-surviving groups based on in-hospital mortality. A total of 153 patients (32 and 121 patients with sepsis and septic shock, respectively) were included from July 2019 to August 2020. Results Among the 153 patients with sepsis, 91 and 62 were in the survivor and non-survivor groups, respectively. Presepsin (p=0.004) and lactate (p=0.003) levels and the sequential organ failure assessment (SOFA) score (p

Background: Endocrine hormones influence tumor progression and the response to treatment. Despite the importance of immune checkpoint inhibitors (ICIs) as treatments for advanced non-small cell lung cancer (NSCLC), few studies have explored the effects of hormone levels in NSCLC patients on the effectiveness of ICI therapies. We thus investigated the effects of baseline blood markers in patients with advanced NSCLC on ICI treatments. Methods: Patients with advanced NSCLC who received programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors at Chungnam National University Hospital between December 2016 and November 2020 and who lacked any history of thyroid gland-related diseases were analyzed retrospectively. We collected clinical information and baseline laboratory data, including the levels of endocrine hormones, cytokines, complete blood counts (CBCs), and peripheral blood chemistry panels. We explored the relationships of hormone levels with clinical outcomes (overall survival [OS], progression-free survival [PFS], and best response), liver metastasis, and blood markers using the Kaplan–Meier method, Cox’s proportional hazards regression, and logistic regression. Results: A total of 113 patients were enrolled. A shorter PFS was independently associated with liver metastasis, higher cortisol levels, and lower hemoglobin (Hb) levels; a shorter OS was associated with liver metastasis, lower tri-iodothyronine (T3) levels, higher lactate dehydrogenase (LDH) levels, and lower albumin levels. Patients with low T3 levels exhibited a shorter PFS and OS, and a poorer best response. Patients with low T3 levels tended to have higher disease progression rates, lower levels of adrenocorticotropic hormone (ACTH), C-peptide, albumin, Hb, and neutrophil-to-lymphocyte ratio, and higher levels of interleukin (IL)-6, white blood cells, platelets, compared with those with normal T3 levels. We found a significant association between a low T3 level and liver metastasis. Conclusions: We found the baseline T3 level was associated with both prognosis and the response to ICIs in patients with advanced NSCLC, probably reflecting impaired liver function and systemic inflammation induced by the interaction of T3 with other biomarkers, such as IL-6, ACTH, cortisol, C-peptide, Hb, LDH, and albumin.

Abstract Objectives The optimal sequence for the administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for treating non‐small cell lung cancer (NSCLC) is still unclear. This study aimed to evaluate the efficacy of sequential afatinib and osimertinib treatment in patients with NSCLC harboring EGFR mutations. Materials and methods Electronic records of patients with EGFR‐mutated NSCLC, who were administered afatinib and osimertinib (group A) or other chemotherapy (group B) between October 2014 and 2019, across 16 hospitals in South Korea were reviewed. The primary outcome, time on treatment (TOT), secondary outcome, and overall survival (OS) were estimated using the Kaplan–Meier method and log‐rank test. Multivariate analyses were performed using the Cox proportional hazards model. Results Of the 737 patients who received frontline afatinib treatment, 324 with complete records were selected (group A: 126, group B: 198). All patients in group A were T790M positive after afatinib, while patients in group B were all negative or unknown. The median TOT was 35.4 months (95% confidence interval [CI]: 27.7−45.6) in group A and 20.8 months (95% CI: 19.4−24.0) in group B. The median TOT with afatinib was 13.0 months (95% CI: 12.0−13.9) overall and 15.7 months (95% CI: 13.9−17.3) in group A. The 2‐ and 3‐year survival rates were 86.0 and 69.3% in group A and 75.9 and 55.3% in group B, respectively. Conclusion Sequential afatinib and osimertinib treatment resulted in better survival rates than treatment with afatinib followed by other chemotherapies.

Abstract Research on species richness patterns and the advanced elevational Rapoport rule (ERR) has been widespread in recent years; however, there is a lack of such research for the temperate mountainous regions in northeast Asia. Here, we collected plant species from the Seorak Mountain in northeast Asia through field surveys. The species were divided into 11 groups according to the life‐form types and phytogeography affinities of each species. The ERR was evaluated using Steven's method and by examining the species richness patterns of each group. The species richness patterns revealed a positive multimodal pattern along the elevation gradient, but phytogeography affinities (increasing trend) and life‐form analysis (unimodal) exhibited different patterns. The elevation gradients (1,350 m for the mean elevation–range relationships), which are affected by the boundary effect and different life forms, did not consistently support the ERR. However, herbs as well as rare, endemic, and red list species showed consistent support for the ERR, which could be attributed to the influence by phytogeography affinities. Therefore, the results from Seorak Mountain showed that the ERR was not consistent for different plant life forms in the same area; however, phytogeography affinities could support and explain ERR.

Abstract Recent data on non-B subtypes’ epidemiology among patients infected with human immunodeficiency virus-1 (HIV-1) in Korea are lacking. We aimed to assess the changing trends in the epidemiology of non-B subtypes of HIV-1 in Korea using phyloepidemiological analyses. We analyzed the demographic records and sequencing data obtained from genotypic drug resistance tests between 2005 and 2019 from 517 patients infected with HIV attending a tertiary care hospital in Busan, Korea. Subtyping and phylogenetic analyses with reference sequences were performed. Additionally, transmission clusters were identified via maximum-likelihood trees. Non-B subtypes accounted for 21.3% of the 517 sequences. CRF01_AE (52.7%) was the most common non-B subtype, followed by CRF02_AG (16.4%), A1 (11.8%), and C (5.5%). The prevalence of non-B subtypes decreased from 36.4 to 13.4% by 2009, while it increased to 27.4% between 2015 and 2019. Among patients with non-B subtypes, the proportion of overseas sailors decreased from 66.7 to 7.5%; contrarily, the proportion of men-who-have-sex-with-men (MSM) increased from 0 to 46.9% over the study period. We identified 8 transmission clusters involving non-B subtypes, with sizes ranging from 2 to 4 patients, including 3 clusters containing MSM. Our results highlight the changes in the epidemiological trends of non-B subtypes of HIV-1 in Korea.

This study aimed to investigate the feasibility of blood-based biomarkers, including blood tumor mutation burden (bTMB), to predict atezolizumab efficacy in relapsed and advanced non-small cell lung cancer (NSCLC). Stage IV NSCLC patients who had previously received platinum-doublet chemotherapy were recruited and received 1200 mg of atezolizumab every three weeks. Blood was collected to obtain plasma cell-free DNA (cfDNA) before the first cycle (C0) and at the fourth cycle (C4). bTMB was measured by CT-ULTRA in patients with cfDNA over 10 ng. The objective response rate (ORR) of the enrolled 100 patients was 10%, and there was no difference in ORR according to bTMB (cutoff: 11.5 muts/Mb) at C0 (high bTMB: 8.1% vs. low bTMB: 11.1%). However, the C4/C0 bTMB ratio was significantly lower in the durable clinical benefit (DCB) patients. The cfDNA concentration at C0, the C4/C0 ratio of the cfDNA concentration, the highest variant allele frequency (hVAF), and the VAF standard deviation (VAFSD) were significantly lower in the DCB patients. In the multivariate analysis, a high cfDNA concentration at C0 (cutoff: 8.6 ng/mL) and a C4/C0 bTMB ratio greater than 1 were significantly associated with progression-free survival. These results suggest that baseline levels and dynamic changes of blood-based biomarkers (bTMB, cfDNA concentration, and VAFSD) could predict atezolizumab efficacy in previously treated NSCLC patients.

Background : : In Korea, in the case of patients with significant bleeding symptoms due to unknown causes, there are very few studies that evaluate bleeding disorders, including von Willebrand disease (VWD). VWD should be considered as an important causative factor in patients with iron deficiency anemia (IDA) and unexplained menorrhagia. This study aimed to understand the clinical characteristics of VWD and the significance of evaluation for VWD in premenopausal women in Korea with menorrhagia and IDA.Methods : : Premenopausal women who were diagnosed with IDA and menorrhagia from January 2009 to March 2020 were included. IDA was diagnosed by either low ferritin or transferrin saturation with microcytic anemia. Menorrhagia was evaluated based on the medical records obtained from a gynecologist. VWD diagnosis was defined as von Willebrand factor antigen

Abstract Background To examine the impact of polymorphisms of glucose transporter 1 (GLUT1) gene on the prognosis of patients with stage III non‐small cell lung cancer (NSCLC) who received radiotherapy. Methods Five single nucleotide polymorphisms (SNPs) (rs4658C>G, rs1385129G>A, rs3820589A>T, rs3806401A>C and rs3806400C>T) in GLUT1 gene were evaluated in 90 patients with pathologically confirmed stage III NSCLC. A total of 21 patients were treated with radiotherapy alone, 25 with sequential chemoradiotherapy, and 44 with concurrent chemoradiotherapy. The association of the genetic variations of five SNPs with overall survival (OS) and progression‐free survival (PFS) was analyzed. Results Two SNPs (rs1385129 and rs3806401) were significant risk factors for OS. Three SNPs (rs1385129, rs3820589 and rs3806401) were in linkage disequilibrium. In Cox proportional hazard models, GAA haplotype was a good prognostic factor for OS (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.39–0.81, p = 0.002) and PFS (HR = 0.68, 95% CI: 0.47–0.99, p = 0.043), compared to variant haplotypes. The GAA/GAA diplotype was observed in 46.7% of patients; these patients showed significantly better OS (HR = 0.38, 95% CI: 0.22–0.65, p

Abstract Background In this study, we investigated the risk factors of acquired T790M mutation among patients with lung adenocarcinoma with epidermal growth factor receptor (EGFR) tyrosine mutation who were treated with EGFR‐tyrosine kinase inhibitors (TKIs). The aim was to identify the clinical impact of rebiopsy. Methods This multicenter, retrospective cohort study was conducted in South Korea from January 2007 to June 2017. Patients with adenocarcinoma with EGFR mutation who underwent rebiopsy and were treated with EGFR‐TKIs were included. Results Of a total of 352 patients, T790M mutation was identified in 156 (41.9%) at the time of rebiopsy. The median duration from initial biopsy to rebiopsy was 17 months. Univariate logistic regression analysis revealed associations of exon 19 deletion (odds ratio [OR], 1.643; p = 0.026), absence of L858R (OR, 0.627; p = 0.042), and previous EGFR‐TKI treatment duration (OR, 1.039; p

Abstract Background Despite the progress of advanced target therapeutic agents and immune checkpoint inhibitors, EGFR‐TKI resistance is still one of the biggest obstacles in treating lung cancer. Clinical studies with autophagy inhibitors are actively underway to overcome drug resistance. Methods We used PC9, PC9/GR, and HCC827/GR cell lines to evaluate the activation of autophagy and EGFR‐TKI resistance. Chloroquine was applied as an autophagic blocker and verteporfin was utilized as a YAP inhibitor. Results In this study, we tried to reveal the effect of autophagy adaptor p62 which is accumulated by autophagy inhibitor in EGFR‐TKI‐resistant lung adenocarcinoma. We identified that p62 has oncogenic functions that induce cell proliferation and invasion of EGFR‐TKI‐resistant lung adenocarcinoma. Interestingly, we found for the first time that YAP regulates p62 transcription through ERK, and YAP inhibition can suppress the expression of oncogenic p62. We also confirmed that the expressions of p62 and YAP have a positive correlation in EGFR‐mutant lung adenocarcinoma patients. To block cell survival via perturbing YAP‐p62 axis, we treated EGFR‐TKI‐resistant lung cancer cells with YAP inhibitor verteporfin. Remarkably, verteporfin effectively caused the death of EGFR‐TKI‐resistant lung cancer cells by decreasing the expressions of p62 with oncogenic function, YAP, and its target PD‐L1. So, the cumulative effect of oncogenic p62 should be considered when using autophagy inhibitors, especially drugs that act at the last stage of autophagy such as chloroquine and bafilomycin A1. Conclusion Finally, we suggest that targeting YAP‐p62 signaling axis can be useful to suppress the EGFR‐TKI‐resistant lung cancer. Therefore, drug repurposing of verteporfin for lung cancer treatment may be valuable to consider because it can inhibit critical targets: p62, YAP, and PD‐L1 at the same time.

Background: The influence of sex on the clinical characteristics and prognosis of coronavirus disease (COVID-19) patients is variable. This study aimed to evaluate COVID-19 management based on sex differences. Methods: We retrospectively reviewed COVID-19 patients who were admitted to the tertiary hospital between January 2020 and March 2021. Logistic regression analysis was used to evaluate the factors associated with in-hospital mortality. Results: During the study period, 584 patients were admitted to our hospital. Among them, 305 patients (52.2%) were female, and 279 patients (47.8%) were male. Males were younger than females, and frailty scale was lower in males than in females. Fever was more common in males, and there was no difference in other initial symptoms. Among the underlying comorbidities, chronic obstructive disease was more common in males, and there were no significant differences in other comorbidities. Moreover, treatment, severity, and outcome did not significantly differ between the groups. The risk factors for in-hospital mortality were age, high white blood cell count, and c-reactive protein level. Conclusions: We found no definite sex differences in the clinical characteristics and outcomes of COVID-19 patients. However, a better understanding of sex-dependent differences in COVID-19 patients could help in understanding and treating patients.

The diffuse sclerosing variant of papillary thyroid carcinoma (DSPTC) is uncommon. Herein, we report a rare case of DSPTC in a 9-year-old girl who initially presented with a painless diffuse goiter. Thyroid peroxidase antibody testing yielded positive results, and the initial clinical diagnosis was Hashimoto’s thyroiditis. However, thyroid ultrasonography revealed characteristic findings of DSPTC, which was confirmed through the postoperative histopathological diagnosis. Although thyroid cancers are rare in the pediatric population, DSPTC should be included in the differential diagnosis of goiter in these patients. Moreover, ultrasonography may prevent a diagnostic delay and facilitate the detection of a concomitant malignancy.

Objective The purpose of this study was to evaluate the risk of osteopenia and osteoporosis by examining the bone mineral density (BMD) of the lumbar spine and femur in patients with gynecological cancer without bone metastasis and to evaluate the impact of treatment for different cancers on BMD. Methods This study retrospectively reviewed the medical records of 243 women with gynecological cancer and 240 controls between March 2010 and December 2016. Patients with cervical cancer (n=105), endometrial cancer (n=63), and ovarian cancer (n=75) were treated with total hysterectomy including bilateral salpingo-oophorectomy and/or chemotherapy and/or radiotherapy. For the control group, healthy post-menopausal women without gynecologic cancer were selected. Results Before anticancer treatment, the BMD of patients with cervical cancer and ovarian cancer was significantly lower than that of the controls, and the BMD of patients with endometrial cancer was not significantly different from that of the controls. However, the BMD of endometrial cancer significantly decreased after treatment. According to the treatment methods, there were significant differences in the BMD of L3, L4, and the femur neck. Changes in the BMD were lowest in patients who underwent surgical treatment only, and the highest bone loss was found in patients who underwent postoperative concurrent chemoradiotherapy. Conclusion Patients with cervical and ovarian cancer had lower BMD than those in the control group before treatment, and patients with endometrial cancer had decreased bone density after treatment. Therefore, during the treatment of gynecological cancer, strategies should be implemented to mitigate these risks.

Abstract Background The resistance of lung cancer to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is one of the unconquered frontiers in chemotherapy. Mitogen-inducible gene 6 (Mig-6) is known to inhibit the kinase activity of epidermal growth factor receptor (EGFR). Similarly, numerous studies of mouse models suggested tumor suppressive function of Mig-6 in lung cancer. On the contrary, the results of clinical investigations revealed that lung cancer patients with elevated expression of Mig-6 are associated with a poor prognosis. More recent work showed that unlike wild type (WT) EGFR, mutant EGFR phosphorylates Mig-6 and phosphorylated Mig-6 negatively regulates the degradation of EGFR mutants in lung adenocarcinoma. Here, we tried to untangle the controversies surrounding Mig-6 function as a protagonist or an antagonist of EGFR-TKI resistant lung cancer. Methods We compared the expression and phosphorylation status of Mig-6 in the EGFR-TKI resistant lung adenocarcinoma (PC9/GR cells) to EGFR-TKI sensitive lung adenocarcinoma (PC9 cells). We investigated the function of Mig-6 by either depletion or overexpression of Mig-6 in those cells and evaluated the efficacy of combining of Mig-6 knock-down and EGFR-TKI treatment in PC9/GR. The correlation between Mig-6 expressions and the prognoses of lung adenocarcinoma was examined by The Cancer Genome Atlas (TCGA) data and clinical samples. Results Our results indicated that the expression of Mig-6 was significantly increased in PC9/GR cells compared to that of PC9 cells. The significant portion of Mig-6 existed as a phosphorylated form in PC9 and PC9/GR cells. Moreover, overexpression of Mig-6 significantly increased the cell proliferation, invasion and epithelial mesenchymal transition (EMT) in PC9 cells. Combination of Mig-6 knock-down and EGFR-TKI treatment significantly overcame the EGFR-TKI resistance of PC9/GR cells. In addition, our analyses of clinical samples confirmed that high Mig-6 expressions positively correlate with a poor prognosis and EGFR-TKI resistance in lung adenocarcinoma. Conclusion Our findings reinforce scientific notion of Mig-6 as an oncoprotein in the context of EGFR-TKI resistant lung adenocarcinoma. We propose that targeting Mig-6 may be a promising strategy to overcome the EGFR-TKI resistance in lung cancer.

Floating-Harbor syndrome is a rare autosomal dominant disorder that presents with short stature, facial dysmorphism, significantly delayed bone age, skeletal abnormalities, speech and language problems, and intellectual disabilities. Although short stature is one of the main clinical manifestations, use of growth hormone therapy in Floating-Harbor syndrome patients has been limited. Only a few reports have investigated the response to growth hormone therapy with regard to final adult height. We report the case of a 7-year-old girl with FloatingHarbor syndrome and a heterozygous mutation, c.7330C > T (p.Arg2444*), in the SRCAP gene. The patient exhibited dysmorphic facial features, severe intellectual disabilities, obsessive-compulsive and aggressive behaviors, and short stature without growth hormone deficiency. Her height standard deviation score improved after 55 months of growth hormone therapy.

ABSTRACT Dysfunctional accessory gene regulator (agr) is associated with unfavorable outcomes in invasive methicillin-resistant Staphylococcus aureus infections. However, it is unknown whether this association persists in methicillin-susceptible Staphylococcus aureus bacteremia (MSSA-B). This study evaluated the association between agr dysfunction and mortality in patients with MSSA-B. This retrospective cohort study included MSSA-B patients (≥15 years) enrolled from June 2014 to June 2019 and retrospectively collected their demographic and clinical information. Stored causative strains were measured for agr functionality by δ-hemolysin production assays. Among 244 MSSA-B patients, 91 (37.3%) and 153 (62.7%) had dysfunctional and functional agr MSSA-B, respectively. Ninety-day mortality occurred in 18.7% and 17.6% dysfunctional and functional groups, respectively (P = 0.97). Kaplan-Meier analysis showed that mortality due to dysfunctional agr MSSA-B was not significantly higher (P = 0.82). Age, sites, the severity of infection, and comorbidity adjusted hazard ratio (aHR) of the dysfunctional group for 90-day mortality was 1.303 (95% confidence interval [CI], 0.698 to 2.436, P = 0.41). Mortality due to MSSA-B with sequential organ failure assessment (SOFA) scores of 2 to 5 was significantly higher in the dysfunctional group (P = 0.03), and the dysfunctional agr aHR for 90-day mortality was 3.260 (95% CI, 1.050 to 10.118, P = 0.04). The agr dysfunction of causative organisms can have a significant effect on the outcomes of MSSA-B in patients with moderate severity (SOFA scores 2 to 5). IMPORTANCE Few studies have examined the association between methicillin-susceptible Staphylococcus aureus (MSSA) infection and accessory gene regulator (agr) functionality. We evaluated the association between agr dysfunction and mortality in patients with MSSA bacteremia. Dysfunctional agr is associated with lower survival in MSSA bacteremia patients with moderately severe sequential organ failure assessment (SOFA) scores of 2 to 5. We found that the agr functionality of causative organisms may have an effect on patients’ outcomes in MSSA like in methicillin-resistant S. aureus.