1.Prognostic Implication of Platelet Reactivity According to Left Ventricular Systolic Dysfunction Status in Patients Treated With Drug-Eluting Stent Implantation:Analysis of the PTRG-DES Consortium
Donghoon HAN ; Sun-Hwa KIM ; Dong Geum SHIN ; Min-Kyung KANG ; Seonghoon CHOI ; Namho LEE ; Byeong-Keuk KIM ; Hyung Joon JOO ; Kiyuk CHANG ; Yongwhi PARK ; Young Bin SONG ; Sung Gyun AHN ; Jung-Won SUH ; Sang Yeub LEE ; Ae-Young HER ; Young-Hoon JEONG ; Hyo-Soo KIM ; Moo Hyun KIM ; Do-Sun LIM ; Eun-Seok SHIN ; Jung Rae CHO ; For the PTRG Investigator
Journal of Korean Medical Science 2024;39(3):e27-
Background:
Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated.
Methods:
From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography. Platelet reactivity was measured using VerifyNow P2Y 12 assay and high platelet reactivity (HPR) was defined as PRU ≥ 252. The major adverse cardiac and cerebrovascular events (MACCEs) were a composite of death, myocardial infarction, stent thrombosis and stroke at 5 years after PCI. Major bleeding was defined as Bleeding Academic Research Consortium bleeding types 3–5.
Results:
A total of 13,160 patients from PTRG-DES, 9,319 (79.6%) patients with the results of both PRU and LVEF were analyzed. The incidence of MACCE and major bleeding was higher in REF group as compared with PEF group (MACCEs: hazard ratio [HR] 2.17, P < 0.001, 95% confidence interval [CI] 1.85–2.55; major bleeding: HR 1.78, P < 0.001, 95% CI 1.39–2.78).The highest rate of MACCEs was found in patients with REF and HPR, and the difference between the groups was statistically significant (HR 3.14 in REF(+)/HPR(+) vs. PEF(+)/HPR(-) group,P <0.01, 95% CI 2.51–3.91). The frequency of major bleeding was not associated with the HPR in either group.
Conclusion
LV dysfunction was associated with an increased incidence of MACCEs and major bleeding in patients who underwent PCI. The HPR status further exhibited significant increase of MACCEs in patients with LV dysfunction in a large, real-world registry.Trial Registration: ClinicalTrials.gov Identifier: NCT04734028
2.Platelet Function and Genotype after DES Implantation in East Asian Patients: Rationale and Characteristics of the PTRG-DES Consortium
Ae-Young HER ; Young-Hoon JEONG ; Byeong-Keuk KIM ; Hyung Joon JOO ; Kiyuk CHANG ; Yongwhi PARK ; Young Bin SONG ; Sung Gyun AHN ; Jung-Won SUH ; Sang Yeup LEE ; Jung Rae CHO ; Hyo-Soo KIM ; Moo Hyun KIM ; Do-Sun LIM ; Eun-Seok SHIN ;
Yonsei Medical Journal 2022;63(5):413-421
Purpose:
Platelet function test (PFT) results and genotype hold unique prognostic implications in East Asian patients. The aim of the PTRG-DES (Platelet function and genoType-Related long-term proGnosis in Drug-Eluting Stent-treated Patients with coronary artery disease) consortium is to assess the clinical impact thereof on long-term clinical outcomes in Korean patients with coronary artery disease during dual antiplatelet therapy (DAPT) including clopidogrel.
Materials and Methods:
Searching publications on the PubMed, we reviewed clopidogrel treatment studies with PFT and/or genotype data for potential inclusion in this study. Lead investigators were invited to share PFT/genotype results, patient characteristics, and clinical outcomes to evaluate relationships among them.
Results:
Nine registries from 32 academic centers participated in the PTRG-DES consortium, contributing individual patient data from 13160 patients who underwent DES implantation between July 2003 and August 2018. The PTRG-PFT cohort was composed of 11714 patients with available VerifyNow assay results. Platelet reactivity levels reached 218±79 P2Y12 reaction units (PRU), and high on-clopidogrel platelet reactivity based on a consensus-recommended cutoff (PRU >208) was observed in 55.9%. The PTRGGenotype cohort consisted of 8163 patients with candidate genotypes related with clopidogrel responsiveness. Of those with cytochrome P450 (CYP) 2C19 genotype, frequencies of carrying one and two loss-of-function allele (s) (*2 or *3) were 47.9% (intermediate metabolizers) and 14.2% (poor metabolizers), respectively.
Conclusion
The PTRG-DES consortium highlights unique values for on-clopidogrel platelet reactivity and CYP2C19 phenotype that may be important to developing optimal antiplatelet regimens in East Asian patients.
3.Sensitivity to tumor development by TALEN-mediated Trp53 mutant genes in the susceptible FVB/N mice and the resistance C57BL/6 mice
Woo Bin YUN ; Ji Eun KIM ; Mi Lim LEE ; Jun Young CHOI ; Jin Ju PARK ; Bo Ram SONG ; Byeong Cheol KANG ; Ki Taek NAM ; Han-Woong LEE ; Dae Youn HWANG
Laboratory Animal Research 2021;37(4):294-306
Background:
This study was undertaken to compare the sensitivities of mice strains during tumor induction by transcription activator-like effector nucleases (TALEN)-mediated Trp53 mutant gene. Alterations of their tumorigenic phenotypes including survival rate, tumor formation and tumor spectrum, were assessed in FVB/N-Trp53 em2Hwl /Korl and C57BL/6-Trp53 em1Hwl /Korl knockout (KO) mice over 16 weeks.
Results:
Most of the physiological phenotypes factors were observed to be higher in FVB/N-Trp53 em2Hwl /Korl KO mice than C57BL/6-Trp53 em1Hwl /Korl KO mice, although there were significant differences in the body weight, immune organ weight, number of red blood cells, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count (PLT), total bilirubin (Bil-T) and glucose (Glu) levels in the KO mice relative to the wild type (WT) mice. Furthermore, numerous solid tumors were also observed in various regions of the surface skin of FVB/N-Trp53 em2Hwl /Korl KO mice, but were not detected in C57BL/6-Trp53 em1Hwl /Korl KO mice. The most frequently observed tumor in both the Trp53 KO mice was malignant lymphoma, while soft tissue teratomas and hemangiosarcomas were only detected in the FVB/N-Trp53 em2Hwl /Korl KO mice.
Conclusions
Our results indicate that the spectrum and incidence of tumors induced by the TALEN-mediated Trp53 mutant gene is greater in FVB/N-Trp53 em2Hwl /Korl KO mice than C57BL/6-Trp53 em1Hwl /Korl KO mice over 16 weeks.
4.Panel-Reactive and Donor-Specific Antibodies before Lung Transplantation can Affect Outcomes in Korean Patients Receiving Lung Transplantation
Sung Woo MOON ; Moo Suk PARK ; Jin Gu LEE ; Hyo Chae PAIK ; Young Tae KIM ; Hyun Joo LEE ; Samina PARK ; Sun Mi CHOI ; Do Hyung KIM ; Woo Hyun CHO ; Hye Ju YEO ; Seung-il PARK ; Se Hoon CHOI ; Sang-Bum HONG ; Tae Sun SHIM ; Kyung-Wook JO ; Kyeongman JEON ; Byeong-Ho JEONG ; Song Yee KIM ;
Yonsei Medical Journal 2020;61(7):606-613
Purpose:
Data on the distribution and impact of panel reactive antibodies (PRA) and donor specific antibodies (DSA) before lung transplantation in Asia, especially multi-center-based data, are limited. This study evaluated the prevalence of and effects of PRA and DSA levels before lung transplantations on outcomes in Korean patients using nationwide multicenter registry data.
Materials and Methods:
This study included 103 patients who received a lung transplant at five tertiary hospitals in South Korea between March 2015 and December 2017. Mortality, primary graft dysfunction (PGD), and bronchiolitis obliterans syndrome (BOS) were evaluated.
Results:
Sixteen patients had class I and/or class II PRAs exceeding 50%. Ten patients (9.7%) had DSAs with a mean fluorescence intensity (MFI) higher than 1000, six of whom had antibodies with a high MFI (≥2000). DSAs with high MFIs were more frequently observed in patients with high-grade PGD (≥2) than in those with no or low-grade (≤1) PGD. In the 47 patients who survived for longer than 9 months and were evaluated for BOS after the transplant, BOS was not related to DSA or PRA levels. One-year mortality was more strongly related to PRA class I exceeding 50% than that under 50% (0% vs. 16.7%, p=0.007).
Conclusion
Preoperative DSAs and PRAs are related to worse outcomes after lung transplantation. DSAs and PRAs should be considered when selecting lung transplant recipients, and recipients who have preoperative DSAs with high MFI values and high PRA levels should be monitored closely after lung transplantation.
5.A Case of Breakthrough COVID-19 during Hydroxychloroquine Maintenance
Byeong Yun AHN ; Chang Kyung KANG ; Jong Do SEO ; Pyoeng Gyun CHOE ; Sang Hoon SONG ; Wan Beom PARK ; Sang Won PARK ; Nam Joong KIM ; Myoung-don OH
Journal of Korean Medical Science 2020;35(24):e231-
There have been controversies on the prophylactic effect of hydroxychloroquine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We describe a patient, 60-year old Korean woman, with coronavirus disease 2019 (COVID-19) who had been taking hydroxychloroquine for 6 months. Her serum and saliva concentrations of hydroxychloroquine were 280 μg/L and 4,890 μg/L, respectively. The present case raises concerns on hydroxychloroquine's role as a prophylactic agent for COVID-19.
6.Characteristics of Lung Allocation and Outcomes of Lung Transplant according to the Korean Urgency Status
Woo Sik YU ; Song Yee KIM ; Young Tae KIM ; Hyun Joo LEE ; Samina PARK ; Sun Mi CHOI ; Do Hyung KIM ; Woo Hyun CHO ; Hye Ju YEO ; Seung il PARK ; Se Hoon CHOI ; Sang Bum HONG ; Tae Sun SHIM ; Kyung Wook JO ; Kyeongman JEON ; Byeong Ho JEONG ; Hyo Chae PAIK ; Jin Gu LEE ;
Yonsei Medical Journal 2019;60(10):992-997
PURPOSE: We investigated the characteristics of lung allocation and outcomes of lung transplant (LTx) according to the Korean urgency status. MATERIALS AND METHODS: LTx registration in the Korean Organ Transplantation Registry (KOTRY) began in 2015. From 2015 to June 2017, 86 patients who received LTx were enrolled in KOTRY. After excluding one patient who received a heart-lung transplant, 85 were included. Subjects were analyzed according to the Korean urgency status. RESULTS: Except for Status 0, urgency status was classified based on partial pressure of oxygen in arterial blood gas analysis and functional status in 52 patients (93%). The wait time for lung allograft was well-stratified by urgency (Status 0, 46.5±59.2 days; Status 1, 104.4±98.2 days; Status 2 or 3, 132.2±118.4 days, p=0.009). Status 0 was associated with increased operative times and higher intraoperative blood transfusion. Status 0 was associated with prolonged extracorporeal membrane oxygenation use, postoperative bleeding, and longer mechanical ventilation after operation. Survival of Status 0 patients seemed worse than that of non-Status 0 patients, although differences were not significant. CONCLUSION: The Korean urgency classification for LTx is determined by using very limited parameters and may not be a true reflection of urgency. Status 0 patients seem to have poor outcomes compared to the other urgency status patients, despite having the highest priority for donor lungs. Further multi-center and nationwide studies are needed to revise the lung allocation system to reflect true urgency and provide the best benefit of lung transplantation.
Allografts
;
Blood Gas Analysis
;
Blood Transfusion
;
Classification
;
Extracorporeal Membrane Oxygenation
;
Hemorrhage
;
Humans
;
Lung Transplantation
;
Lung
;
Operative Time
;
Organ Transplantation
;
Oxygen
;
Partial Pressure
;
Respiration, Artificial
;
Tissue Donors
;
Transplants
7.Magnifying Endoscopy for Esophageal Ectopic Sebaceous Glands.
Mu Song JEON ; Gwang Ha KIM ; Dong Young JEONG ; Byeong Kyu PARK ; Moon Won LEE ; So Jeong LEE ; Do Youn PARK
Clinical Endoscopy 2018;51(5):495-497
Ectopic sebaceous glands are found very rarely in the esophagus; heretofore, several cases have been reported. The sebaceous gland is originally a source of an endodermal origin; however, there have been controversies regarding whether the origin of the esophageal ectopic sebaceous gland is ectodermal or endodermal. Ectopic sebaceous glands of the esophagus usually do not cause symptoms; thus, they are often found incidentally on endoscopy for routine health screening. Endoscopic findings are characterized by single or multiple yellow patches or nodular lesions of various sizes, sometimes with small central openings. We report two cases of esophageal ectopic sebaceous glands found incidentally during endoscopy with magnifying endoscopic findings. The lesions were in the mid-esophagus and lower esophagus, respectively, and both endoscopic findings were similar as multiple yellowish patches or plaques. Magnifying endoscopy revealed the openings of the excretory ducts surrounded by circular microvessels in both cases.
Ectoderm
;
Endoderm
;
Endoscopy*
;
Esophagus
;
Mass Screening
;
Microvessels
;
Sebaceous Glands*
8.Factor Analysis of Intraoperative Radical Conversion During Partial Nephrectomy: Single Surgeon Experience.
Dong Hwan LEE ; Woo Heon CHA ; Younsoo CHUNG ; Tae Jin KIM ; In Jae LEE ; Byeong Do SONG ; Sangchul LEE ; Sung Kyu HONG ; Jong Jin OH ; Seok Soo BYUN
Korean Journal of Urological Oncology 2017;15(3):165-171
PURPOSE: Preoperative aspects and dimensions used for an anatomical (PADUA) classification is useful to predict perioperative complications and warm ischemia time. However, it remains uncertain whether PADUA classification can predict intraoperative conversion from partial nephrectomy (PN) to radical nephrectomy (RN). We evaluate whether PADUA classification parameters can predict conversion to RN during PN. MATERIALS AND METHODS: We retrospectively assessed data of 593 patients who underwent open PN and robotic PN for renal tumors by a single surgeon at a single tertiary center between December 2003 and September 2017. Intraoperative conversion to RN was performed in 17 of 593 patients who initially underwent PN. We evaluated the factors influencing the surgical modalities including PN and radical conversion cases. Then, the factors significantly associated with conversion to RN were further analyzed. RESULTS: There were no significant differences between the 2 groups in age, longitudinal location, exophytic rate, and rim or face locations of renal masses. Renal sinus involvement, urinary collecting system involvement, and renal mass size were variables that predicted radical conversion, using univariate analysis. Renal sinus involvement (odds ratio [OR], 9.075; p=0.049) and urinary collecting system involvement (OR, 3.944; p=0.029) were independent predictors of intraoperative radical conversion, using multivariate analysis. CONCLUSIONS: The PADUA classification is a useful tool to predict intraoperative conversion from PN to RN. Renal sinus involvement and urinary collecting system involvement are the best predictors of intraoperative conversion from PN to RN.
Classification
;
Factor Analysis, Statistical*
;
Humans
;
Multivariate Analysis
;
Nephrectomy*
;
Retrospective Studies
;
Surgical Procedures, Operative
;
Warm Ischemia
9.Comparison of Localized High Volume Tumor and Locally Advanced Low Volume Tumor after Radical Prostatectomy according to Risk Classification.
Tae Jin KIM ; In Jae LEE ; Byeong Do SONG ; Sang Chul LEE ; Sung Kyu HONG ; Seok Soo BYUN ; Sang Eun LEE ; Jong Jin OH
Korean Journal of Urological Oncology 2016;14(3):165-171
PURPOSE: To investigate the percentage of pathologic tumor volume (pTPV) among patients who underwent radical prostatectomy (RP). MATERIALS AND METHODS: We reviewed 3,080 patients who underwent RP between September 2003 and March 2015 and with a postoperative follow-up for more than 1 year. The patient population was stratified into 4 disease risk groups according to tumor stage and pTPV (T2 low volume [T2LV], T2 high volume [T2HV], T3 low volume [T3LV], and T3 high volume [T3HV]). Probability of biochemical recurrence (BCR)-free survival was determined using Kaplan-Meier curves. pTPV was evaluated by Multivariate Cox proportional hazard analysis for predicting BCR. Subgroup analyses were performed according to preoperative risk. RESULTS: The median prostate-specific antigen (PSA) was 7.87 ng/mL, and pTPV was 10%. Among a total of 2,964 patients, T2LV had 1,473 (49.7%), T2HV was 598 (20.2%), T3LV with 199 (6.7%), and T3HV was 694 (23.4%). When comparing T2HV and T3LV, Gleason score and positive surgical margin rate was higher in T3LV. During a 50-month follow-up, BCR-free survival rate was higher in the T2HV group (p<0.001). pTPV was a significant factor to predict BCR in multivariate Cox analysis. In subgroup analyses, T2HV group had similar BCR-free survival rates to T3LV group in the preoperative high risk group while pTPV was significant in the high risk group. CONCLUSIONS: pTPV was a significant predictor of BCR among prostate cancer patients after RP, however T2HV had favorable BCR results. Among patients with a preoperative high PSA and Gleason score, T2HV had similar BCR results to T3LV.
Classification*
;
Follow-Up Studies
;
Humans
;
Neoplasm Grading
;
Prostate
;
Prostate-Specific Antigen
;
Prostatectomy*
;
Prostatic Neoplasms
;
Recurrence
;
Survival Rate
;
Tumor Burden
10.Clinical Significance of Positive Surgical Margin after Radical Prostatectomy according to Pathological Stage.
In Jae LEE ; Jong Jin OH ; Tae Jin KIM ; Byeong Do SONG ; Sangchul LEE ; Sung Kyu HONG ; Sang Eun LEE ; Seok Soo BYUN
Korean Journal of Urological Oncology 2016;14(3):159-164
PURPOSE: The purpose of this study was to investigate the positive surgical margin (PSM) as a predictive factor of biochemical recurrence (BCR) in prostate cancer (PCa) patients after radical prostatectomy (RP) according to each pathological stage. MATERIALS AND METHODS: The records of 3,037 patients receiving RP were retrospectively reviewed. All patients were divided into 6 groups depending on pathological stage and presence of PSM. Cox proportional hazard analyses were performed to show the significance of PSM in all patients and in subgroup patients (T2, T3a, and T3b). The Kaplan-Meier analysis showed BCR-free survival rate of each group. RESULTS: Among total 3.307 patients, the mean age was 65.89 years and PSM rate was 18.7%. During the 47.1 months, 550 patients had experienced BCR (26.2%). According to groups, prostate-specific antigen, Gleason score, and BCR were significantly different. Ten-year BCR-free survival rate was 87.1% (T2R0), 65.9% (T2R1), 60.1% (T3aR0), 43.0% (T3aR1), 20.8% (T3bR0), and 5.8% (T3bR1). Each group had statistical differences with BCR-free survival except T2R1 and T3aR0 (p=0.090). PSM was significant in multivariate Cox analyses in total patients (hazard ratio, 2.091; 95% confidence interval, 1.724–2.536; p<0.001) and in all subgroup with each stages. CONCLUSIONS: PSM is a significant predictor to BCR after RP in all PCa patients and in each stage. T2R1 PCa had a similar BCR-free survival rate to T3R0 patients during long-term follow-up, therefore careful management to T2R1 PCa as T3 should be necessary.
Follow-Up Studies
;
Humans
;
Kaplan-Meier Estimate
;
Neoplasm Grading
;
Passive Cutaneous Anaphylaxis
;
Prostate-Specific Antigen
;
Prostatectomy*
;
Prostatic Neoplasms
;
Recurrence
;
Retrospective Studies
;
Survival Rate

Result Analysis
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