1.Pioneering PGC-1αα–boosted secretome: a novel approach to combating liver fibrosis
Chang Ho SEO ; Gun Hyung NA ; Dosang LEE ; Jung Hyun PARK ; Tae Ho HONG ; Ok-Hee KIM ; Sang Chul LEE ; Kee-Hwan KIM ; Ho Joong CHOI ; Say-June KIM
Annals of Surgical Treatment and Research 2024;106(3):155-168
Purpose:
Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis.
Methods:
Upon achieving a cellular confluence of 70%–80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vitro mouse models.
Results:
In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to the control-secretome. In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum proinflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec–treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, optic atrophy 1 (a mitochondrial function marker), and peroxisome proliferator-activated receptor alpha (an antifibrogenic marker) in the PGC-Sec–treated group, along with reduced collagen type 1A expression (a profibrogenic marker).
Conclusion
These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.
2.Recommendations for Adult Immunization by the Korean Society of Infectious Diseases, 2023: Minor Revisions to the 3rd Edition
Won Suk CHOI ; Joon Young SONG ; Ki Tae KWON ; Hyo-Jin LEE ; Eun Ju CHOO ; Jihyeon BAEK ; BumSik CHIN ; Woo Joo KIM ; Mi Suk LEE ; Wan Beom PARK ; Sang Hoon HAN ; Jun Yong CHOI ; Joon Sup YEOM ; Jin-Soo LEE ; Hee-Jung CHOI ; Young Hwa CHOI ; Dong-Gun LEE ; Jung-Hyun CHOI ; Hee Jin CHEONG ;
Infection and Chemotherapy 2024;56(2):188-203
The Korean Society of Infectious Diseases has been regularly developing guidelines for adult immunization since 2007. In 2023, the guidelines for the following seven vaccines were revised: influenza, herpes zoster, pneumococcal, tetanus-diphtheria-pertussis (Tdap), human papillomavirus (HPV), meningococcal, and rabies vaccines. For the influenza vaccine, a recommendation for enhanced vaccines for the elderly was added. For the herpes zoster vaccine, a recommendation for the recombinant zoster vaccine was added. For the pneumococcal vaccine, the current status of the 15-valent pneumococcal conjugate vaccine and 20-valent PCV was described. For the Tdap vaccine, the possibility of using Tdap instead of tetanus-diphtheria vaccine was described. For the HPV vaccine, the expansion of the eligible age for vaccination was described. For the meningococcal vaccine, a recommendation for the meningococcal B vaccine was added. For the rabies vaccine, the number of pre-exposure prophylaxis doses was changed. This manuscript documents the summary and rationale of the revisions for the seven vaccines. For the vaccines not mentioned in this manuscript, the recommendations in the 3rd edition of the Vaccinations for Adults textbook shall remain in effect.
4.Five-Year Overall Survival and Prognostic Factors in Patients with Lung Cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015
Da Som JEON ; Ho Cheol KIM ; Se Hee KIM ; Tae-Jung KIM ; Hong Kwan KIM ; Mi Hyung MOON ; Kyongmin Sarah BECK ; Yang-Gun SUH ; Changhoon SONG ; Jin Seok AHN ; Jeong Eun LEE ; Jeong Uk LIM ; Jae Hyun JEON ; Kyu-Won JUNG ; Chi Young JUNG ; Jeong Su CHO ; Yoo-Duk CHOI ; Seung-Sik HWANG ; Chang-Min CHOI ; ;
Cancer Research and Treatment 2023;55(1):103-111
Purpose:
This study aimed to provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015.
Materials and Methods:
The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung Cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020.
Results:
We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with non–small cell lung cancer (NSCLC) and 345 (13.0%) were diagnosed with small cell lung cancer (SCLC), respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of epidermal growth factor receptor (EGFR) mutation (19% vs. 11%) or anaplastic lymphoma kinase (ALK) translocation (38% vs. 11%).
Conclusion
In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.
5.Impacts of Subtype on Clinical Feature and Outcome of Male Breast Cancer: Multicenter Study in Korea (KCSG BR16-09)
Jieun LEE ; Keun Seok LEE ; Sung Hoon SIM ; Heejung CHAE ; Joohyuk SOHN ; Gun Min KIM ; Kyung-Hee LEE ; Su Hwan KANG ; Kyung Hae JUNG ; Jae-ho JEONG ; Jae Ho BYUN ; Su-Jin KOH ; Kyoung Eun LEE ; Seungtaek LIM ; Hee Jun KIM ; Hye Sung WON ; Hyung Soon PARK ; Guk Jin LEE ; Soojung HONG ; Sun Kyung BAEK ; Soon Il LEE ; Moon Young CHOI ; In Sook WOO
Cancer Research and Treatment 2023;55(1):123-135
Purpose:
The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea.
Materials and Methods:
We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016.
Results:
The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003).
Conclusion
Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.
6.Migratory Pneumonia in Prolonged SARS-CoV-2 Infection in Patients Treated With B-cell Depletion Therapies for B-cell Lymphoma
Jongmin LEE ; Raeseok LEE ; Kyongmin Sarah BECK ; Dae Hee HAN ; Gi June MIN ; Suyon CHANG ; Jung Im JUNG ; Dong-Gun LEE
Korean Journal of Radiology 2023;24(4):362-370
Objective:
To report the clinical and radiological characteristics of patients with underlying B-cell lymphoma and coronavirus disease 2019 (COVID-19) showing migratory airspace opacities on serial chest computed tomography (CT) with persistent COVID-19 symptoms.
Materials and Methods:
From January 2020 to June 2022, of the 56 patients with underlying hematologic malignancy who had undergone chest CT more than once at our hospital after acquiring COVID-19, seven adult patients (5 female; age range, 37–71 years; median age, 45 years) who showed migratory airspace opacities on chest CT were selected for the analysis of clinical and CT features.
Results:
All patients had been diagnosed with B-cell lymphoma (three diffuse large B-cell lymphoma and four follicular lymphoma) and had received B-cell depleting chemotherapy, including rituximab, within three months prior to COVID-19 diagnosis. The patients underwent a median of 3 CT scans during the follow-up period (median 124 days). All patients showed multifocal patchy peripheral ground glass opacities (GGOs) with basal predominance in the baseline CTs. In all patients, followup CTs demonstrated clearing of previous airspace opacities with the development of new peripheral and peribronchial GGO and consolidation in different locations. Throughout the follow-up period, all patients demonstrated prolonged COVID-19 symptoms accompanied by positive polymerase chain reaction results from nasopharyngeal swabs, with cycle threshold values of less than 25.
Conclusion
COVID-19 patients with B-cell lymphoma who had received B-cell depleting therapy and are experiencing prolonged SARS-CoV-2 infection and persistent symptoms may demonstrate migratory airspace opacities on serial CT, which could be interpreted as ongoing COVID-19 pneumonia.
7.Diagnosis and treatment of hereditary angioedema: An expert opinion
Jae-Woo JUNG ; So-Young PARK ; Sun Young YOON ; Gun-Woo KIM ; Kyoung-Hee SOHN ; Sung-Yoon KANG ; Hye Jung PARK ; Min-Kyu KANG ; Joo-Hee KIM ; Kyung Hee PARK ; Dong In SUH ; Dong Hun LEE ; Sae-Hoon KIM ; Hyouk-Soo KWON ; Hye-Ryun KANG
Allergy, Asthma & Respiratory Disease 2022;10(2):80-88
Hereditary angioedema (HAE) is a rare disease, but it severely interrupts daily life activities and can sometimes be life-threatening. Therefore, early diagnosis and prompt treatment of HAE attacks are critical. Physicians should be aware of how to diagnose and manage HAE to prepare not to miss a diagnosis when treating HAE patients. Physicians must also carry out tests to confirm the diagnosis of HAEs caused by C1 inhibitor deficiency (type 1) or C1 inhibitor dysfunction (type 2) in patients with recurrent angioedema. In addition, recent studies revealed another type of HAE which is not related to C1 inhibitor (normal C1 inhibitor HAE). Once HAE is confirmed, patients and their caregivers should be given with short-term and long-term treatment plans to relieve or prevent HAE attacks. HAE requires life-long measures, including psychological support for patients and self-management education.
8.Biomarker-guided targeted therapy in platinum-resistant ovarian cancer (AMBITION; KGOG 3045): a multicentre, open-label, five-arm, uncontrolled, umbrella trial
Jung-Yun LEE ; Byoung-Gie KIM ; Jae-Weon KIM ; Jung Bok LEE ; Eunhyang PARK ; Je-Gun JOUNG ; Sunghoon KIM ; Chel Hun CHOI ; Hee Seung KIM ;
Journal of Gynecologic Oncology 2022;33(4):e45-
Objective:
Management of heavily pre-treated platinum-resistant ovarian cancer remains a therapeutic challenge. Outcomes are poor with non-platinum, single-agent chemotherapy (CT); however, molecularly targeted anticancer therapies provide new options.
Methods:
This open-label, investigator-initiated, phase 2 umbrella trial (NCT03699449) enrolled patients with platinum-resistant ovarian cancer (at least 2 prior lines of CT and Eastern Cooperative Oncology Group 0/1) to receive combination therapy based on homologous recombination deficiency (HRD) and programmed death ligand 1 (PD-L1) status determined by archival tumour sample assessment. HRD-positive patients were randomised to either olaparib 200mg bid tablet + cediranib 30mg qd (arm 1) or olaparib 300mg bid tablet + durvalumab 1,500mg q4w (arm 2). HRD-negative patients were allocated to either durvalumab 1,500 mg q4w + pegylated liposomal doxorubicin (PLD) or topotecan or weekly paclitaxel (6 cycles; arm 3, those with PD-L1 expression) or durvalumab 1,500 mg q4w + tremelimumab 75mg q4w (4 doses) + PLD or topotecan or weekly paclitaxel (4 cycles; arm 4, those without PD-L1 expression). Arm 5 (durvalumab 1,500 mg q4w + tremelimumab 300mg [1 dose] + weekly paclitaxel [60 mg/m2 D1,8,15 q4w for 4 cycles] was initiated after arm 4 completed. The primary endpoint was objective response rate (ORR; Response Evaluation Criteria in Solid Tumours 1.1).
Results:
Between Dec 2018 and Oct 2020, 70 patients (median 57 years; median 3 prior treatment lines [range 2–10]) were treated (n=16, 14, 5, 18, and 17, respectively). Overall ORR was 37.1% (26/70, 95% confidence interval=25.9, 49.5); 2 achieved complete response. ORR was 50%, 42.9%, 20%, 33.3%, and 29.4%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients, respectively. No TRAEs leading to treatment discontinuation and no grade 5 TRAEs were observed.
Conclusion
This study, the first biomarker-driven umbrella trial in platinum-resistant recurrent ovarian cancer, suggests clinical utility with biomarker-driven targeted therapy. All treatment combinations were manageable, and without unexpected toxicities.
9.Management of hereditary angioedema in pediatric, pregnant, and breast-feeding patients: An expert opinion
Sun Young YOON ; Jae-Woo JUNG ; So Young PARK ; Gun-Woo KIM ; Kyunghee SON ; Sung-Yoon KANG ; Hye Jung PARK ; Min-Kyu KANG ; Joo-Hee KIM ; Kyung Hee PARK ; Dong Hun LEE ; Sae-Hoon KIM ; Hyouk-Soo KWON ; Hye-Ryun KANG ; Dong In SUH
Allergy, Asthma & Respiratory Disease 2022;10(3):131-138
Hereditary angioedema (HAE) is a rare inherited condition marked by recurrent skin and submucosal edema. HAE is caused by a C1 inhibitor deficiency or decreased C1 inhibitor function. The initial attack may occur during childhood or pregnancy, with symptoms ranging from classic angioedema to nonspecific stomach cramps. In this review, we discuss strategies for children and pregnant women to manage HAE attacks effectively and safely in light of the recent increase in HAE diagnosis. To begin, aggressive work-up is necessary to confirm HAE–1/2 and to determine the most effective countermeasures. Secondly, in the event of an acute attack, plasma-derived C1-inhibitor is the first line of defense for children and pregnant women. Icatibant is also appropriate for use, except in pregnant women. Fresh frozen plasma (FFP) may be suggested as an alternative. Thirdly, proactive measures to prevent HAE attacks should be considered whenever a procedure is performed that may result in an exacerbation. Finally, FFP, attenuated androgen and antifibrinolytic agents are recommended for long-term prophylaxis in South Korea where the C1-inhibitor is scarce. However, when making a decision, it is necessary to consider both the efficacy and the risk of adverse effects. For proper management, written action plans and first-aid kits are required. The action plans should be customized to the patients‘ unique circumstances.
10.Effect of fever or respiratory symptoms on leaving without being seen during the COVID-19 pandemic in South Korea
Dohyung KIM ; Weon JUNG ; Jae Yong YU ; Hansol CHANG ; Se Uk LEE ; Taerim KIM ; Sung Yeon HWANG ; Hee YOON ; Tae Gun SHIN ; Min Seob SIM ; Ik Joon JO ; Won Chul CHA
Clinical and Experimental Emergency Medicine 2022;9(1):1-9
Objective:
Coronavirus disease 2019 (COVID-19) has notably altered the emergency department isolation protocol, imposing stricter requirements on probable infectious disease patients that enter the department. This has caused adverse effects, such as an increased rate of leave without being seen (LWBS). This study describes the effect of fever/respiratory symptoms as the main cause of isolation regarding LWBS after the COVID-19 pandemic.
Methods:
We retrospectively analyzed emergency department visits before (March to July 2019) and after (March to July 2020) the COVID-19 pandemic. Patients were grouped based on existing fever or respiratory symptoms, with the LWBS rate as the primary outcome. Logistic regression analysis was used to identify the risk factors of LWBS. Logistic regression was performed using interaction terminology (fever/respiratory symptom patient [FRP] × post–COVID-19) to determine the interaction between patients with FRPs and the COVID-19 pandemic period.
Results:
A total of 60,290 patients were included (34,492 in the pre–COVID-19, and 25,298 in the post–COVID-19 group). The proportion of FRPs decreased significantly after the pandemic (P < 0.001), while the LWBS rate in FRPs significantly increased from 2.8% to 19.2% (P < 0.001). Both FRPs (odds ratio, 1.76; 95% confidence interval, 1.59–1.84 (P < 0.001) and the COVID-19 period (odds ratio, 2.29; 95% confidence interval, 2.15–2.44; P < 0.001) were significantly associated with increased LWBS. Additionally, there was a significant interaction between the incidence of LWBS in FRPs and the COVID-19 pandemic period (P < 0.001).
Conclusion
The LWBS rate has increased in FRPs after the COVID-19 pandemic; additionally, the effect observed was disproportionate compared with that of nonfever/respiratory symptom patients.

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