1.Longitudinal Comparative Analysis of Circulating Tumor DNA and Matched Tumor Tissue DNA in Patients with Metastatic Colorectal Cancer Receiving Palliative First-Line Systemic Anti-Cancer Therapy
Seung-been LEE ; Ji-Won KIM ; Hong-Geun KIM ; Sung-Hyun HWANG ; Kui-Jin KIM ; Ju Hyun LEE ; Jeongmin SEO ; Minsu KANG ; Eun Hee JUNG ; Koung Jin SUH ; Se Hyun KIM ; Jin Won KIM ; Yu Jung KIM ; Jee Hyun KIM ; Nak-Jung KWON ; Keun-Wook LEE
Cancer Research and Treatment 2024;56(4):1171-1182
Purpose:
This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy.
Materials and Methods:
We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data.
Results:
Among 208 consecutively enrolled patients, we selected 84 (41 males; median age, 59 years; range, 35 to 90 years) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, seven mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival.
Conclusion
While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer’s clonal evolution. Additionally, baseline-ctDNA’s VAF values were prognostic after treatment.
2.The Profile of Early Sedation Depth and Clinical Outcomes of Mechanically Ventilated Patients in Korea
Dong-gon HYUN ; Jee Hwan AHN ; Ha-Yeong GIL ; Chung Mo NAM ; Choa YUN ; Jae-Myeong LEE ; Jae Hun KIM ; Dong-Hyun LEE ; Ki Hoon KIM ; Dong Jung KIM ; Sang-Min LEE ; Ho-Geol RYU ; Suk-Kyung HONG ; Jae-Bum KIM ; Eun Young CHOI ; JongHyun BAEK ; Jeoungmin KIM ; Eun Jin KIM ; Tae Yun PARK ; Je Hyeong KIM ; Sunghoon PARK ; Chi-Min PARK ; Won Jai JUNG ; Nak-Jun CHOI ; Hang-Jea JANG ; Su Hwan LEE ; Young Seok LEE ; Gee Young SUH ; Woo-Sung CHOI ; Keu Sung LEE ; Hyung Won KIM ; Young-Gi MIN ; Seok Jeong LEE ; Chae-Man LIM
Journal of Korean Medical Science 2023;38(19):e141-
Background:
Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known.
Methods:
From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups.
Results:
Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582).
Conclusion
In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.
3.Antibiotic Prescription in Patients With Coronavirus Disease 2019:Analysis of National Health Insurance System Data in the Republic of Korea
Yunsang CHOI ; Minsun KANG ; Dong Hoon SHIN ; Jongtak JUNG ; Seong Jin CHOI ; Nak-Hyun KIM ; Song Mi MOON ; Kyoung-Ho SONG ; Eu Suk KIM ; Jaehun JUNG ; Hong Bin KIM
Journal of Korean Medical Science 2023;38(25):e189-
Background:
Although coronavirus disease 2019 (COVID-19) is a viral infection, antibiotics are often prescribed due to concerns about accompanying bacterial infection. Therefore, we aimed to analyze the number of patients with COVID-19 who received antibiotic prescriptions, as well as factors that influenced antibiotics prescription, using the National Health Insurance System database.
Methods:
We retrospectively reviewed claims data for adults aged ≥ 19 years hospitalized for COVID-19 from December 1, 2019 to December 31, 2020. According to the National Institutes of Health guidelines for severity classification, we calculated the proportion of patients who received antibiotics and the number of days of therapy per 1,000 patient-days. Factors contributing to antibiotic use were determined using linear regression analysis. In addition, antibiotic prescription data for patients with influenza hospitalized from 2018 to 2021 were compared with those for patients with COVID-19, using an integrated database from Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service cohort (K-COV-N cohort), which was partially adjusted and obtained from October 2020 to December 2021.
Results:
Of the 55,228 patients, 46.6% were males, 55.9% were aged ≥ 50 years, and most patients (88.7%) had no underlying diseases. The majority (84.3%; n = 46,576) were classified as having mild-to-moderate illness, with 11.2% (n = 6,168) and 4.5% (n = 2,484) having severe and critical illness, respectively. Antibiotics were prescribed to 27.3% (n = 15,081) of the total study population, and to 73.8%, 87.6%, and 17.9% of patients with severe, critical, and mild-to-moderate illness, respectively. Fluoroquinolones were the most commonly prescribed antibiotics (15.1%; n = 8,348), followed by third-generation cephalosporins (10.4%; n = 5,729) and beta-lactam/beta-lactamase inhibitors (6.9%; n = 3,822). Older age, COVID-19 severity, and underlying medical conditions contributed significantly to antibiotic prescription requirement. The antibiotic use rate was higher in the influenza group (57.1%) than in the total COVID-19 patient group (21.2%), and higher in severe-to-critical COVID-19 cases (66.6%) than in influenza cases.
Conclusion
Although most patients with COVID-19 had mild to moderate illness, more than a quarter were prescribed antibiotics. Judicious use of antibiotics is necessary for patients with COVID-19, considering the severity of disease and risk of bacterial co-infection.
4.Real-world Prescription Patterns and Patient Satisfaction Regarding Maintenance Therapy of Gastroesophageal Reflux Disease: An Observational, Cross-sectional, Multicenter Study
Cheal Wung HUH ; Nak Hoon SON ; Young Hoon YOUN ; Da Hyun JUNG ; Min Kyung KIM ; Eun Jeong GONG ; Kyu Chan HUH ; Seung Young KIM ; Moo In PARK ; Ju Yup LEE ; Joong Goo KWON ; Jae Hak KIM ; Cheol Min SHIN ; Kee Wook JUNG ; Su Jin HONG ; Hee Man KIM ; Suck Chei CHOI ; Hye-Kyung JUNG ; Hyun Jin KIM ; Kwang Jae LEE
Journal of Neurogastroenterology and Motility 2023;29(4):470-477
Background/Aims:
Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that typically requires long-term maintenance therapy. However, little is known about patient preferences and satisfaction and real-world prescription patterns regarding maintenance therapy for GERD.
Methods:
This observational, cross-sectional, multicenter study involved patients from 18 referral hospitals in Korea. We surveyed patients who had been prescribed proton pump inhibitors (PPIs) for GERD for at least 90 days with a minimum follow-up duration of 1 year. The main outcome was overall patient satisfaction with different maintenance therapy modalities.
Results:
A total of 197 patients were enrolled. Overall patient satisfaction, patient preferences, and GERD health-related quality of life scores did not significantly differ among the maintenance therapy modality groups. However, the on-demand therapy group experienced a significantly longer disease duration than the continuous therapy group. The continuous therapy group demonstrated a lower level of awareness of potential adverse effects associated with PPIs than the on-demand therapy group but received higher doses of PPIs than the on-demand therapy group. The prescribed doses of PPIs also varied based on the phenotype of GERD, with higher doses prescribed for non-erosive reflux disease than erosive reflux disease.
Conclusion
Although overall patient satisfaction did not significantly differ among the different PPI maintenance therapy modality groups, awareness of potential adverse effects was significantly different between the on-demand and continuous therapy groups.
5.The size of pelvic hematoma can be a predictive factor for angioembolization in hemodynamically unstable pelvic trauma
Hak Jae LEE ; Hyo Keun NO ; Nak Joon CHOI ; Hyun Woo SUN ; Jae Suk LEE ; Yoon Joong JUNG ; Suk Kyung HONG
Annals of Surgical Treatment and Research 2020;98(3):146-152
PURPOSE:
Unstable pelvic fracture with bleeding can be fatal, with a mortality rate of up to 40%. Therefore, early detection and treatment are important in unstable pelvic trauma. We investigated the early predictive factors for possible embolization in patients with hemodynamically unstable pelvic trauma.
METHODS:
From January 2011 to December 2013, 46 patients with shock arrived at a single hospital within 24 hours after injury. Of them, 44 patients underwent CT scan after initial resuscitation, except for 2 who were dead on arrival. Nine patients with other organ injuries were excluded. Seventeen patients underwent embolization. A single radiologist measured the width (longest length in axial view) and length (longest length in coronal view) of pelvic hematoma on CT scans. Demographic, clinical, and radiological data were reviewed retrospectively.
RESULTS:
Among 35 patients with hemodynamically unstable pelvic fracture, 22 (62.9%) were men. Width (P = 0.002) and length (P = 0.006) of hematoma on CT scans were significantly different between the embolization and nonembolization groups. The predictors of embolization were width of pelvic hematoma (odds ratio [OR], 1.07; P = 0.028) and female sex (OR, 10.83; P = 0.031). The cutoff value was 3.35 cm. More embolization was performed (OR, 12.00; P = 0.003) and higher mortality was observed in patients with hematoma width >3.35 cm (OR, 4.96; P = 0.048).
CONCLUSION
Patients with hemodynamically unstable pelvic trauma have a high mortality rate. CT is useful for the initial identification of the need for embolization among these patients. The width of pelvic hematoma can predict possible embolization in patients with unstable pelvic trauma.
6.Cardiac Manifestations of Coronavirus Disease 2019 (COVID-19): a Multicenter Cohort Study
Minkwan KIM ; Jong-Ho NAM ; Jang-Won SON ; Sun Oh KIM ; Nak-Hoon SON ; Chul-Min AHN ; Chi Young SHIM ; Geu-Ru HONG ; In-Cheol KIM ; Jinwoo CHOI ; Seung-Mo KANG ; Yeoung Ho CHOI ; Hae Kyoung YOON ; Jae-Sun UHM ; In Hyun JUNG
Journal of Korean Medical Science 2020;35(40):e366-
Background:
This study aimed to investigate the cardiac manifestations of coronavirus disease 2019 (COVID-19).
Methods:
From February to March 2020, we prospectively and retrospectively enrolled consecutive patients diagnosed with COVID-19. Patient's data such as the demographic characteristics, symptoms, vital signs, laboratory and radiologic findings, electrocardiographic, and echocardiographic data, including the global longitudinal strain (GLS) of both ventricles, were obtained.
Results:
Forty patients (median age, 58 years; 50% men) were enrolled in the initial analysis. Patients were classified into severe and nonsevere groups based on the current guidelines. The 13 patients in the severe group were significantly older, had a greater prevalence of bilateral pneumonia and leukocytosis, and higher aspartate transaminase levels than patients in the nonsevere group. Patients in the severe group had a slightly lower left ventricular ejection fraction (LVEF) than those in the nonsevere group (median [interquartile range], 61.0% [58.5%, 62.3%] vs. 66.7% [60.6%, 69.8%], P = 0.015). In a subgroup of 34 patients in whom GLS could be analyzed, patients in the severe group had a significantly impaired left ventricular GLS (LVGLS) than those in the nonsevere group (−18.1% [−18.8%, −17.1%] vs. −21.7% [−22.9%, −19.9%], P = 0.001). There were no significant differences in total wall (RVGLS total , −19.3% [−23.9%, −18.4%] vs. −24.3% [−26.0%, −22.6%], P = 0.060) and free wall (RVGLS fw , −22.7% [−27.2%, −18.6%] vs. −28.8% [−30.4%, −24.1%], P = 0.066) right ventricle GLS (RVGLS).
Conclusion
Patients with severe COVID-19 had lower LVEF and LVGLS. RVGLS was not different between patients with severe and nonsevere COVID-19.
7.The comparison of surgical outcomes and learning curves of radical hysterectomy by laparoscopy and robotic system for cervical cancer: an experience of a single surgeon.
Yoon Jung HEO ; Seongmin KIM ; Kyung Jin MIN ; Sanghoon LEE ; Jin Hwa HONG ; Jae Kwan LEE ; Nak Woo LEE ; Jae Yun SONG
Obstetrics & Gynecology Science 2018;61(4):468-476
OBJECTIVE: The aim of this study was to compare and determine the feasibility, surgical outcomes, learning curves of robotic radical hysterectomy with lymph node dissection (RRHND) to conventional laparoscopic radical hysterectomy with lymph node dissection (LRHND) performed by a single surgeon, in patients with cervical cancer. METHODS: Between April 2009 and March 2013, 22 patients underwent LRHND and 19 patients underwent RRHND. Variables such as age, body mass index, International Federation of Gynecology and Obstetrics stage, histological results, number of dissected lymph nodes, operative time, estimated blood loss, days of hospitalization and complications were reviewed. Learning curves of operation time was obtained using cumulative sum (CUSUM) method. RESULTS: Both groups showed similar patient and tumor characteristics. In surgical outcome analysis, RRHND (51.8±10.4 minutes) showed longer preparing time than LRHND (42.5±14.1 minutes). In the LRHND group, 8 patients experienced postoperative complications (5 void difficulty, 1 postoperative bleeding, 1 right basal ganglia infarction, 1 fever). On the other hand, in the RRHND group, 4 patients experienced a postoperative complication (2 bleeding, 1 peritonitis, 1 dehiscence of trocar site). Using CUSUM method, the learning curves were obtained by plotting the cumulative sequential differences between each data point and the average operation time, and showed two distinct phases in both type of operations. CONCLUSION: RRHND would be appropriate surgical approach in patients with cervical cancer with favorable outcome of less voiding difficulty. A minimum of 13 cases of robotic radical hysterectomies are required to achieve surgical improvement in the treatment of cervical cancer.
Basal Ganglia
;
Body Mass Index
;
Gynecology
;
Hand
;
Hemorrhage
;
Hospitalization
;
Humans
;
Hysterectomy*
;
Infarction
;
Laparoscopy*
;
Learning Curve*
;
Learning*
;
Lymph Node Excision
;
Lymph Nodes
;
Methods
;
Minimally Invasive Surgical Procedures
;
Obstetrics
;
Operative Time
;
Peritonitis
;
Postoperative Complications
;
Surgical Instruments
;
Uterine Cervical Neoplasms*
8.Clinical Outcomes of Diffuse Axonal Injury According to Radiological Grade
Hak Jae LEE ; Hyun Woo SUN ; Jae Seok LEE ; Nak Joon CHOI ; Yoon Joong JUNG ; Suk Kyung HONG
Journal of the Korean Society of Traumatology 2018;31(2):51-57
PURPOSE:
Patients with diffuse axonal injury experience various disabilities and have a high cost of treatment. Recent researches have revealed the underlying mechanism and pathogenesis of diffuse axonal injury. This study aimed to investigate the correlation between the radiological grading of diffuse axonal injury and the clinical outcomes of patients.
METHODS:
From January 2011 to December 2016, among 294 patients with traumatic brain injury, 44 patients underwent magnetic resonance imaging (MRI). A total of 18 patients were enrolled in this study except for other cerebral injuries, such as cerebral hemorrhage or hypoxic brain damage. Demographic data, clinical data, and radiological findings were retrospectively reviewed. The grading of diffuse axonal injury was analyzed based on patient's MRI findings.
RESULTS:
For the most severe diffuse axonal injury patients, prolonged intensive care unit (ICU) stay (p=0.035), hospital stay (p=0.012), and prolonged mechanical ventilation (p=0.030) were observed. However, there was no significant difference in healthcare-associated infection rates between MRI grading (p=0.123). Massive transfusion, initial hemoglobin and lactate levels, and MRI gradings were found to be highly significant in predicting the duration of unconsciousness.
CONCLUSIONS
This study showed that patients with high grade diffuse axonal injury have prolonged ICU stays and significantly longer hospital stays. Deteriorated mental patients with high energy injuries should be evaluated to identify diffuse axonal injuries by using an appropriate imaging tool, such as MRI. It will be important to predict the duration of consciousness recovery using MRI scans.
9.Isolation of Middle East Respiratory Syndrome Coronavirus from a Patient of the 2015 Korean Outbreak.
Wan Beom PARK ; Nak Jung KWON ; Pyoeng Gyun CHOE ; Su Jin CHOI ; Hong Sang OH ; Sang Min LEE ; Hyonyong CHONG ; Jong Il KIM ; Kyoung Ho SONG ; Ji Hwan BANG ; Eu Suk KIM ; Hong Bin KIM ; Sang Won PARK ; Nam Joong KIM ; Myoung Don OH
Journal of Korean Medical Science 2016;31(2):315-320
During the 2015 outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Korea, 186 persons were infected, resulting in 38 fatalities. We isolated MERS-CoV from the oropharyngeal sample obtained from a patient of the outbreak. Cytopathic effects showing detachment and rounding of cells were observed in Vero cell cultures 3 days after inoculation of the sample. Spherical virus particles were observed by transmission electron microscopy. Full-length genome sequence of the virus isolate was obtained and phylogenetic analyses showed that it clustered with clade B of MERS-CoV.
Animals
;
Cercopithecus aethiops
;
Coronavirus Infections/*diagnosis/epidemiology/*virology
;
Disease Outbreaks
;
Humans
;
Microscopy, Electron
;
Middle East Respiratory Syndrome Coronavirus/classification/genetics/*isolation & purification/ultrastructure
;
Phylogeny
;
Polymerase Chain Reaction
;
RNA, Viral/analysis/chemistry/metabolism
;
Republic of Korea/epidemiology
;
Sequence Analysis, RNA
;
Vero Cells
10.Fatal Rectal Bleeding after Prostate Biopsy.
Min Jung KIM ; Jae Hong PARK ; Byung Ha CHOI ; Nak Eun CHUNG
Korean Journal of Legal Medicine 2012;36(1):111-114
Transrectal ultrasound (TRUS)-guided biopsy of the prostate is a common outpatient procedure for diagnosing prostatic cancer. It is a relatively noninvasive, safe, and effective method, as the majority of post-biopsy complications are mild and self-limiting. Fatal complications including infection or massive hemorrhage are rare, but can be life threatening. We herein present an autopsy case of fatal rectal bleeding after prostate biopsy and an analysis of similar cases.
Autopsy
;
Biopsy
;
Hemorrhage
;
Humans
;
Outpatients
;
Prostate
;
Prostatic Neoplasms

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