1.Prediction of Mid-term Platelet Transfusion in Stable Trauma Patients Using Rotational Thromboelastometry
Ha Jin LIM ; Hyunseok JANG ; Naa LEE ; Euisung JEONG ; Yunchul PARK ; Younggoun JO ; Jungchul KIM ; Young Eun LEE ; Hyun-Jung CHOI ; Seung-Jung KEE ; Jong Hee SHIN ; Myung Geun SHIN
Annals of Laboratory Medicine 2024;44(1):74-81
Background:
Rotational thromboelastometry (ROTEM; TEM International GmbH, Munich, Germany) is a global coagulation test that guides evidence-based platelet transfusion in trauma patients. We evaluated ROTEM parameters for predicting mid-term (five days) platelet transfusion in trauma patients.
Methods:
Maximum clot firmness and clot amplitudes after 5, 10, and 15 mins (A5, A10, and A15, respectively) of fibrin-specific ROTEM (FIBTEM) and extrinsically activated ROTEM (EXTEM) were retrospectively collected from 82 hospitalized, stable, non-bleeding trauma patients after successful initial resuscitation. Platelet-specific ROTEM (PLTEM) was calculated by subtracting FIBTEM from EXTEM. Platelet transfusions were reviewed for five days after ROTEM.
Results:
The areas under the curve for FIBTEM, EXTEM, and PLTEM predicting platelet concentrate transfusion of > 12 U at mid-term were 0.915–0.923, 0.878–0.896, and 0.551–0.735, respectively. FIBTEM and EXTEM parameters were comparable to those of fibrinogen, fibrin/fibrinogen degradation products, D-dimer, and antithrombin III. Strong correlations (r > 0.7) were noted between platelet count and EXTEM (A5, A10, and A15) or PLTEM (A5), platelet function (per platelet count) and EXTEM (A10 and A15), and fibrinogen levels and all FIBTEM parameters.
Conclusions
FIBTEM and EXTEM can reliably predict mid-term platelet transfusion in trauma patients. FIBTEM, EXTEM, and PLTEM parameters correlate with conventional coagulation tests (platelets and fibrinogen).
2.The Real-World Outcome of First Line Atezolizumab in Extensive-Stage Small Cell Lung Cancer: A Multicenter Prospective Cohort Study
Myeong Geun CHOI ; Yeon Joo KIM ; Jae Cheol LEE ; Wonjun JI ; In-Jae OH ; Sung Yong LEE ; Seong Hoon YOON ; Shin Yup LEE ; Jeong Eun LEE ; Eun Young KIM ; Chang-Min CHOI
Cancer Research and Treatment 2024;56(2):422-429
Purpose:
The addition of immune checkpoint inhibitors to chemotherapy has improved survival outcomes in patients with extensive-stage small cell lung cancer (ES-SCLC). However, their real-world effectiveness remains unknown. Therefore, we investigated the effectiveness of atezolizumab plus chemotherapy in ES-SCLC in actual clinical settings.
Materials and Methods:
In this multicenter prospective cohort study, patients with ES-SCLC receiving or scheduled to receive atezolizumab in combination with etoposide and carboplatin were enrolled between June 2021 and August 2022. The primary outcomes were progression-free survival (PFS) and the 1-year overall survival (OS) rate.
Results:
A total of 100 patients with ES-SCLC were enrolled from seven centers. Median age was 69 years, and 6% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2. The median PFS was 6.0 months, the 1-year OS rate was 62.2%, and the median OS was 13.5 months. An ECOG PS of 2-3 and progressive disease as the best response were poor prognostic factors for PFS, while an ECOG PS of 2-3 and brain metastasis were associated with poor prognosis for OS. In addition, consolidative thoracic radiotherapy was found to be an independent favorable prognostic factor for OS (hazard ratio, 0.336; p=0.021). Grade ≥ 3 treatment-related adverse events were observed in 7% of patients, with treatment-related deaths occurring in 2% of patients.
Conclusion
We provided evidence of the favorable real-world effectiveness and safety of atezolizumab plus chemotherapy in ES-SCLC patients, including in the elderly and those with poor ECOG PS. Additional consolidative thoracic radiotherapy may also benefit ES-SCLC patients.
3.International Digestive Endoscopy Network consensus on the management of antithrombotic agents in patients undergoing gastrointestinal endoscopy
Seung Joo KANG ; Chung Hyun TAE ; Chang Seok BANG ; Cheol Min SHIN ; Young-Hoon JEONG ; Miyoung CHOI ; Joo Ha HWANG ; Yutaka SAITO ; Philip Wai Yan CHIU ; Rungsun RERKNIMITR ; Christopher KHOR ; Vu Van KHIEN ; Kee Don CHOI ; Ki-Nam SHIM ; Geun Am SONG ; Oh Young LEE ;
Clinical Endoscopy 2024;57(2):141-157
Antithrombotic agents, including antiplatelet agents and anticoagulants, are widely used in Korea because of the increasing incidence of cardiocerebrovascular disease and the aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. The clinical practice guidelines for this issue, developed by the Korean Society of Gastrointestinal Endoscopy, were published in 2020. However, new evidence on the use of dual antiplatelet therapy and direct anticoagulant management has emerged, and revised guidelines have been issued in the United States and Europe. Accordingly, the previous guidelines were revised. Cardiologists were part of the group that developed the guideline, and the recommendations went through a consensus-reaching process among international experts. This guideline presents 14 recommendations made based on the Grading of Recommendations, Assessment, Development, and Evaluation methodology and was reviewed by multidisciplinary experts. These guidelines provide useful information that can assist endoscopists in the management of patients receiving antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.
4.Clinical Practice Guideline for Percutaneous Endoscopic Gastrostomy
Chung Hyun TAE ; Ju Yup LEE ; Moon Kyung JOO ; Chan Hyuk PARK ; Eun Jeong GONG ; Cheol Min SHIN ; Hyun LIM ; Hyuk Soon CHOI ; Miyoung CHOI ; Sang Hoon KIM ; Chul-Hyun LIM ; Jeong-Sik BYEON ; Ki-Nam SHIM ; Geun Am SONG ; Moon Sung LEE ; Jong-Jae PARK ; Oh Young LEE ;
Gut and Liver 2024;18(1):10-26
With an aging population, the number of patients with difficulty swallowing due to medical conditions is gradually increasing. In such cases, enteral nutrition is administered through a temporary nasogastric tube. Long-term use of a nasogastric tube leads to various complications and a decreased quality of life. Percutaneous endoscopic gastrostomy (PEG) is the percutaneous placement of a tube into the stomach, aided endoscopically, which may be an alternative to a nasogastric tube when enteral nutritional is required for 4 weeks or more. This paper is the first Korean clinical guideline for PEG. It was developed jointly by the Korean College of Helicobacter and Upper Gastrointestinal Research and led by the Korean Society of Gastrointestinal Endoscopy. These guidelines aimed to provide physicians, including endoscopists, with the indications, use of prophylactic antibiotics, timing of enteric nutrition, tube placement methods, complications, replacement, and tubes removal for PEG based on the currently available clinical evidence.
5.International Digestive Endoscopy Network Consensus on the Management of Antithrombotic Agents in Patients Undergoing Gastrointestinal Endoscopy
Seung Joo KANG ; Chung Hyun TAE ; Chang Seok BANG ; Cheol Min SHIN ; Young-Hoon JEONG ; Miyoung CHOI ; Joo Ha HWANG ; Yutaka SAITO ; Philip Wai Yan CHIU ; Rungsun RERKNIMITR ; Christopher KHOR ; Vu Van KHIEN ; Kee Don CHOI ; Ki-Nam SHIM ; Geun Am SONG ; Oh Young LEE ; The Korean Society of Gastrointestinal Endoscopy Task Force on Clinical Practice Guidelines
Gut and Liver 2024;18(5):764-780
Antithrombotic agents, including antiplatelet agents and anticoagulants, are widely used in Korea because of the increasing incidence of cardiocerebrovascular disease and the aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. The clinical practice guidelines for this issue, developed by the Korean Society of Gastrointestinal Endoscopy, were published in 2020. However, new evidence on the use of dual antiplatelet therapy and direct anticoagulant management has emerged, and revised guidelines have been issued in the United States and Europe. Accordingly, the previous guidelines were revised. Cardiologists were part of the group that developed the guideline, and the recommendations went through a consensus-reaching process among international experts. This guideline presents 14 recommendations made based on the Grading of Recommendations, Assessment, Development, and Evaluation methodology and was reviewed by multidisciplinary experts. These guidelines provide useful information that can assist endoscopists in the management of patients receiving antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.
6.Suppression of Glioblastoma Stem Cell Potency and Tumor Growth via LRRK2 Inhibition
Saewhan PARK ; Kyung-Hee KIM ; Yun-Hee BAE ; Young Taek OH ; Hyemi SHIN ; Hyung Joon KWON ; Chan Il KIM ; Sung Soo KIM ; Hwan-Geun CHOI ; Jong Bae PARK ; Byoung Dae LEE
International Journal of Stem Cells 2024;17(3):319-329
Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson’s disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors.Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.
7.Prognostic Factors for Predicting Post-COVID-19 Condition in Patients With COVID-19 in an Outpatient Setting
Myeong Geun CHOI ; Young Woong JOO ; Min-Ho KIM ; Sojung PARK ; Yune-Young SHIN ; Eun Mi CHUN
Journal of Korean Medical Science 2024;39(2):e23-
Background:
Although data on post-coronavirus disease 2019 (COVID-19) conditions are extensive, the prognostic factors affecting symptom duration in non-hospitalized patients with COVID-19 are currently not well known. We aimed to investigate the various prognostic factors affecting symptom duration among outpatients with COVID-19.
Methods:
Data were analyzed from 257 patients who were diagnosed with mild COVID-19 and visited the ‘post-COVID-19 outpatient clinic’ between April and December 2022 after a mandatory isolation period. The symptom duration was measured from diagnosis to symptom resolution. Laboratory and pulmonary function test results from their first visit were collected.
Results:
The mean age of patients was 55.7 years, and the median symptom duration was 57 days. The development of post-COVID-19 conditions (> 12 weeks) were significantly correlated with not using antiviral drugs, leukocytosis (white blood cell > 10,000/µL), lower 25(OH)D 3 levels, forced vital capacity (FVC) < 90% predicted, and presence of dyspnea and anxiety/depression. Additionally, in multivariable Cox regression analysis, not using antiviral drugs, lower 25(OH)D 3 levels, and having dyspnea were poor prognostic factors for longer symptom duration. Particularly, vitamin D deficiency (< 20 ng/mL) and not using antivirals during the acute phase were independent poor prognostic factors for both post-COVID-19 condition and longer symptom duration.
Conclusion
The non-use of antivirals, lower 25(OH)D 3 levels, leukocytosis, FVC < 90% predicted, and the presence of dyspnea and anxiety/depression symptoms could be useful prognostic factors for predicting post-COVID-19 condition in outpatients with COVID-19. We suggest that the use of antiviral agents during the acute phase and vitamin D supplements might help reduce COVID-19 symptom duration.
8.Comparison between Focal Laser Photocoagulation and Intravitreal Bevacizumab Injection for Treating Chronic Central Serous Chorioretinopathy
Young Bin YOON ; Woo Seok CHOI ; Kyoo Won LEE ; Dong-Geun PARK
Journal of the Korean Ophthalmological Society 2024;65(4):277-284
Purpose:
We compared the efficacy of focal laser photocoagulation and intravitreal bevacizumab injection in the treatment of chronic central serous chorioretinopathy.
Methods:
We conducted a retrospective analysis involving 46 eyes of 46 patients with chronic central serous chorioretinopathy who received focal laser photocoagulation (22 eyes) or intravitreal bevacizumab injection (24 eyes). Changes in best-corrected visual acuity (BVCA), central macular thickness, and rates of complete subretinal fluid (SRF) resolution and recurrence were compared over a 6-month period.
Results:
Although the focal laser photocoagulation and intravitreal bevacizumab injection groups demonstrated a significant reduction in central macular thickness at 6 months (p < 0.001), no statistically significant differences were observed between these groups at the end of the follow-up period. Notably, a gradual improvement in BVCA was observed in both groups following initial treatment, with significant improvement seen at 6 months (p = 0.049 and p = 0.048 for the laser and injection groups, respectively). However, no statistically significant difference in BVCA improvement was observed between the groups. Complete SRF resolution was achieved in 22 eyes in the laser group and 23 eyes in the injection group. Although recurrence of SRF was observed in 9 and 13 eyes in the laser and injection groups, respectively, there was no statistically significant difference between the groups (p = 0.229).
Conclusions
Focal laser photocoagulation and intravitreal bevacizumab injection significantly improved anatomical and visual acuity outcomes in patients with chronic central serous chorioretinopathy. Although focal laser photocoagulation was associated with more rapid visual recovery and a lower recurrence rate compared to intravitreal bevacizumab injection, further studies are needed to evaluate its potential complications.
9.IDEN Consensus on Management of Antithrombotic Agents in Patients Undergoing Gastrointestinal Endoscopy
Seung Joo KANG ; Chung Hyun TAE ; Chang Seok BANG ; Cheol Min SHIN ; Young-Hoon JEONG ; Miyoung CHOI ; Joo Ha HWANG ; Yutaka SAITO ; Philip Wai Yan CHIU ; Rungsun RERKNIMITR ; Christopher KHOR ; Vu Van KHIEN ; Kee Don CHOI ; Ki-Nam SHIM ; Geun Am SONG ; Oh Young LEE ;
The Korean Journal of Gastroenterology 2024;83(6):217-232
Antithrombotic agents, including antiplatelet agent and anticoagulants are widely used in Korea due to increasing incidence of cardio-cerebrovascular disease and aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. Clinical practice guideline regarding this issue which was developed by the Korean Society of Gastrointestinal Endoscopy was published in 2020. However, since then, new evidence has emerged for the use of dual antiplatelet therapy and direct anticoagulant management, and revised guidelines were issued in the US and Europe. Accordingly, the previous guidelines were revised, cardiologists also participated in the development group, and the recommendations went through a consensus process among international experts. This guideline presents 14 recommendations made according to the Grading of Recommendations, Assessment, Development, and Evaluation methodology, and was reviewed by multidisciplinary experts. This guideline provides useful information that can assist endoscopists in the management of patients on antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.
10.Profiling of endogenous metabolites and changes in intestinal microbiota distribution after GEN-001 (Lactococcus lactis) administration
Min-Gul KIM ; Suin KIM ; Ji-Young JEON ; Seol Ju MOON ; Yong-Geun KWAK ; Joo Young NA ; SeungHwan LEE ; Kyung-Mi PARK ; Hyo-Jin KIM ; Sang-Min LEE ; Seo-Yeon CHOI ; Kwang-Hee SHIN
The Korean Journal of Physiology and Pharmacology 2024;28(2):153-164
This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control.Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 1011 colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5–6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

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