소아 IgA 신병증의 예후와 관련한 임상병리학적 고찰

권재훈,최은나,박지민,정현주,이재승,Kwon Jae-Hun,Choi Eun-Na,Park Jee-Min,Jeung Hyeun-Joo,Lee Jae-Seung 대한소아신장학회 2003 Childhood kidney diseases Vol.7 No.1

목적 : IgA 신병증으로 진단된 소아환자를 대상으로 질병의 예후와 관련된 연구는 부족한 상태이다. 이에 저자들은 조직생검을 통해 확진된 IgA 신병증 환아의 임상경과를 관찰함으로써 소아들에서 장기 예후에 영향을 줄 수 있는 인자들의 특성을 알아보고자 하였다. 대상 및 방법 : 1981년부터 2000년까지 연세의료원에서 신생검을 시행하여 병리 소견상 IgA 신병증으로 확진된 15세 이하의 57명 환아에서 후향적 방법으로 자료 분석을 시행하였다. 모든 환아들은 조직 생검 당시 혈뇨나 무증후성 단백뇨($<40\;mg/m^2/day$)를 보였으며 정상 신기능 및 혈압을 유지하였다. 진단 당시의 임상검사소견, 병리소견 등을 바탕으로 IgA 신병증의 합병증인 심한 단백뇨(${\ge}40\;mg/m^2/day$), 약물복용을 요하는 고혈압. 만성 신부전 등의 발생에 대해 관찰하였다. 결과 : 대상 환아들의 진단 시 평균 연령은 4세에서 15세까지 $9.5{\pm}2.8$세였으며 42명(74%)이 남자였다. 단독 육안적 혈뇨는 20명(35%), 단독 현미경적 혈뇨는 3명(5%)이며 단독 단백뇨는 15(26%)이었다. 육안적 혈뇨와 단백뇨를 같이 동반한 경우는 15명(26%)이며 현미경적 혈뇨와 단백뇨는 15명(26%)에서 보였다. $7.0{\pm}3.5$년의 평균추적 관찰 기간동안 전체 57명의 환아 중 단백뇨 및 혈뇨가 완전히 소실된 경우는 38명(67%)이었고 진단 당시처럼 혈뇨나 단백뇨가 지속되나 IgA 신병증의 부작용은 발생하지 않은 경우는 12명(21%)이었다. 반면, 단지 7명(12%)의 환아에게서 IgA 신병증의 합병증이 발생하였는데 이 중에서 신증후군 정도의 단백뇨는 4명(7%), 약물복용을 요하는 고혈압은 1명(2%)이었고 2명(4%)의 환아는 말기 신부전으로 이행하였다. 발병 연령을10세 전후로 나누었을 때(P<0.01)와 Lee와 Haas의 병리조직학적인 분류(P<0.05)는 IgA 신병증의 합병증 발생과 밀접한 연관을 보인 반면, 진단당시 증상이나 성별은 통계적 유의성을 보이지 않았다. 57명 중 7명의 환아에서 평균 $3.4{\pm}3.5$년후에 신조직검사를 재실시하였다. 이 중 3명의 환아는 처음 class와 같았으며, 1명의 환아는 class III에서 class IV로 진행된 반면, 3명의 환아는 class IV에서 각각 class I, class II 및 class III로 변하였다. 결론 : 본 연구를 통해 소아의 IgA 신병증은 더 이른 시기에 진단 받았을 때 합병증의 발생 및 궁극적인 신부전으로의 이행이 적게 나타났다. 또한 추적 신조직 검사상 조직의 변화소견을 볼 때, 소아 IgA 신병증이 성인에서의 것보다 더 좋은 예후를 보이는 근거가 될 수 있다. Purpose : This study was performed to determine the natural history of histologically confirmed IgA nephropathy in pediatric patients who presented with hematuria and proteinuria. Patients and Methods : We reviewed the clinical course of 57 patients diagnosed with IgA nephropathy at the age of 15 years or younger from 1981 to 2000. All patients presented with hematuria or minimal proteinuria($<40\;mg/m^2/day$) and had normal renal function and blood pressure at the time of renal biopsy. Based on the clinical and pathological findings at the time of diagnosis, we sought for complications of IgA nephropathy such as heavy proteinuria(${\ge}40\;mg/m^2/day$), hypertension, and chronic renal failure. Results : The mean age at presentation was $9.5{\pm}2.8$ years(4 to 15 years) and 42(74%) were male. Isolated gross hematuria was observed in 20 patients(35%), microscopic hematuria in 3(5%), minimal proteinuria in 4(7%), both gross hematuria and minimal proteinuria in 15(26%), and both microscopic hematuria and minimal proteinuria in 15(26%). During a median follow-up of $7.0{\pm}3.5$ years, 38(67%) had complete resolution of hematuria and proteinuria, 12(21%) had persistently abnormal urinalysis without development of adverse events. Only 7(12%) developed adverse events : 4(7%) developed severe proteinuria, 1(2%) became hypertensive, and 2(3%) developed Impaired renal function. By univariate analysis using the chisquare test, the age at presentation(>10 years)(P<0.01) and poor histological classes of the Lee or Haas classification at onset(P<0.05) were significantly correlated with adverse events, whereas sex and clinical signs at onset were less concordant. Conclusion : We can conclude that the prognosis of IgA nephropathy diagnosed in early childhood is better and a good correlation exists between the clinical manifestations of this disease and the histological classes.

Different Number of Sessions of Intense Pulsed Light and Meibomian Gland Expression Combination Therapy for Meibomian Gland Dysfunction

Seung Hyeun Lee(Seung Hyeun Lee),Minjeong Kim(Minjeong Kim),Won Jun Lee(Won Jun Lee),Yeoun Sook Chun(Yeoun Sook Chun),Kyoung Woo Kim(Kyoung Woo Kim) 대한안과학회 2022 Korean Journal of Ophthalmology Vol.36 No.6

Purpose: To evaluate the effect of the intense pulsed light (IPL) and meibomian gland (MG) expression (MGX) combination therapy according to the total numbers of sessions in the meibomian gland dysfunction (MGD). Methods: Ninety patients with MGD were included. Patients had maximal five sessions of IPL (Aqua Cel, Jeisys Medical) and MGX combination therapy at 2-week intervals. The ocular surface disease index (OSDI) questionnaire score, MG profile grades, tear matrix metalloproteinase-9 (MMP-9), tear break-up time (BUT), tear osmolarity, tear secretion, and corneal erosions were evaluated. Results: The number of patients who had a total of one to five sessions (1S to 5S) was 10, 25, 17, 20, and 18, respectively. The time-serial decrease of OSDI scores was significant in patients who had three or more sessions (3S, p = 0.002; 4S, p < 0.001; 5S, p < 0.001). The MG expressibility grade decreased with two or more sessions (2S–5S, p < 0.001), but the meibum quality significantly improved with all sessions (1S, p = 0.012; 2S, p = 0.024; 3S, p = 0.015; 4S, p < 0.001; 5S, p < 0.001). Although tear BUT increased even in patients with one session (1S, p = 0.040; 3S, p = 0.005; 4S, p = 0.006; 5S, p = 0.021), tear MMP-9, osmolarity, Schirmer I, and corneal erosions were not improved in every number of sessions. The female sex was the sole contributor to the final symptomatic improvement (p = 0.042), and the MGD stages were not related to the final OSDI decrease. Conclusions: The OSDI score, MGD grades, and BUT were improved after the IPL and MGX combination therapy in MGD patients. Unlike MGD grades and tear film instability might be improved just after a few sessions, the overall subjective relief was accomplished in three or more sessions.

Reactive oxygen species modulator 1 (Romo1) as a diagnostic marker for Lung cancer-related malignant effusion

( Seung Hyeun Lee ),( Sue In Choi ),( Won Jai Jung ),( Eun Joo Lee ),( Kyung Hoon Min ),( Gyu Young Hur ),( Seung Heon Lee ),( Sung Yong Lee ),( Je Hyeong Kim ),( Sang Yeub Lee ),( Chol Shin ),( Jae J 대한결핵 및 호흡기학회 2015 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.120 No.-

Background: Reactive oxygen species modulator 1 (Romo1) is a novel protein that plays an important role in intracellular reactive oxygen species generation. Recently, serum and tissue Romo1 was suggested as a diagnostic and prognostic marker, respectively, for non-small cell lung cancer. We evaluated the clinical usefulness of pleural fluid Romo1 measurement for the diagnosis of malignant effusion in lung cancer patients. Methods: Romo1 level was measured in pleural fluid using enzyme-linked immunosorbent assay in four groups: lung cancer-associated malignant effusion (n =56; 26 adenocarcinomas, 26 squamous cell carcinomas and 4 small cell lung cancers), tuberculous pleurisy (n = 31), parapneumonic effusion (n =30) and transudate (n = 30). The discriminative power for lung cancer-associated malignant effusion was determined using receiver operating characteristic curve analysis. Results: Median Romo1 level in lung cancer-associated malignant effusion was 99.1 ng/mL which is significantly higher compared with other groups (all p < 0.001). The optimal cutoff value of Romo1 for lung cancer-associated malignant effusion was 67.0 ng/mL with a sensitivity of 73.9% and specificity of 84.1%, with an area under the curve of 0.814 (95% confidence interval : 0.730 - 0.866, p = 0.0001). Conclusion: Romo1 discriminated lung cancer-associated malignant effusion from non-malignant effusions with considerable sensitivity and specificity. Pleural fluid Romo1 could be a potential diagnostic marker for lung cancer-associated malignant effusion.

Reactive oxygen species modulator 1 (Romo1) predict poor outcome in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy

( Seung Hyeun Lee ),( Sue In Choi ),( Won Jai Jung ),( Eun Joo Lee ),( Kyung Hoon Min ),( Gyu Young Hur ),( Seung Heon Lee ),( Sung Yong Lee ),( Je Hyeong Kim ),( Sang Yeub Lee ),( Chol Shin ),( Jae J 대한결핵 및 호흡기학회 2015 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.120 No.-

Background: Reactive oxygen species modulator 1 (Romo1) is key mediator of intracellular reactive oxygen species production. Increased expression of Romo1 has been reported in human malignancies and was associated with poor survival in lung cancer patients who undergo surgery. We investigated whether Romo1 expression is associated with clinical outcomes of patients who were treated with platinum-based chemotherapy for advanced non-small cell lung cancer (NSCLC). Methods: Romo1 expression in tumor tissues was examined by immunohistochemistry and evaluated by a semiquantitative histologic score (H score). We performed survival analyses and evaluated the association between Romo1 expression and clinical parameters. Results: A total of 81 tumor specimens were available for Romo1 evaluation. At the cutoff value of H score 200, multivariate analysis showed that high Romo1 expression was significantly associated with short progression-free survival (hazard ratio [HR] = 4.40, 95% confidence interval [CI]: 2.54 -7.62), and with short overall survival (HR = 3.00, 95% CI: 2.88-5.02). Romo1 expression was not associated with any clinical parameter including age, gender, smoking status, stage, differentiation, or tumor histology. Conclusion: Increased Romo1 expression was associated with poor response and short overall survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 overexpression could be a potential adverse prognostic marker in this setting.

Rapid Detection of Mycobacterium tuberculosis Using a Novel Ultrafast Chip-Type Real-Time Polymerase Chain Reaction System

Lee, Seung Hyeun,Kim, Sung-Woo,Lee, Sehyun,Kim, EunSub,Kim, Duck-Joong,Park, Sohyun,Lee, Eun Joo,Lee, Sang Yeub,Lee, Ji Sung,Lim, Chae Seung,Kim, Won-Ki,In, Kwang Ho Elsevier 2014 Chest Vol.146 No.5

<P>NBS LabChip G2-3 is a novel, ultrafast, chip-type portable real-time polymerase chain reaction (PCR) system. We evaluated the clinical usefulness of this system in detecting pulmonary TB and assessed its diagnostic performance compared with a conventional tube-type PCR system.</P>

수술을 시행한 비소세포 폐암 환자에서 EGFR, MMP-9 및 C-erbB-2의 발현과 환자 생존율과의 관계

이승헌 ( Seung Heon Lee ),정진용 ( Jin Yong Jung ),이경주 ( Kyoung Ju Lee ),이승현 ( Seung Hyeun Lee ),김세중 ( Se Joong Kim ),하은실 ( Eun Sil Ha ),김정하,이은주 ( Eun Joo Lee ),허규영 ( Gyu Young Hur ),정기환 ( Ki Hwan Jung ),정혜 대한결핵 및 호흡기학회 2005 Tuberculosis and Respiratory Diseases Vol.59 No.3

리포다당질에 의한 급성폐손상에서 Ethyl Pyruvate의 효과

이승현 ( Seung Hyeun Lee ),윤대위 ( Dae Wui Yoon ),정진용 ( Jin Yong Jung ),이경주 ( Kyung Joo Lee ),김세중 ( Se Joong Kim ),이은주 ( Eun Joo Lee ),강은해 ( Eun Hae Kang ),정기환 ( Ki Hwan Jung ),이승룡 ( Sung Yong Lee ),이상엽 ( 대한결핵 및 호흡기학회 2006 Tuberculosis and Respiratory Diseases Vol.61 No.4

연구배경: 급성폐손상에서 활성산소종에 의한 산화 손상은 주요한 역할을 한다. Ethyl pyruvate (EP)는 체내에서 생성되는 pyruvate의 유도체로 항산화 및 항염증 효과가 있음이 알려졌다. 저자들은 리포다당질에 의한 급성폐손상 모델에서 EP가 염증반응에 미치는 영향을 연구하고자 하였다. 방법: 5주 령의 BALB/c 생쥐를 이용하여 리포다당질을 기관 내로 투여하여 급성폐손상을 유도하였다. 대조군, LPS군, EP+LPS군, LPS+EP군으로 나누어 기관지폐포세척액에서 TNF-α, IL-6 및 myelo-peroxidase (MPO)의 활성을, 폐조직에서 급성폐손상지수와 NF-κB의 농도를 측정하였다. 결과: EP+LPS군에서 TNF-α및 IL-6의 농도는 LPS군과 비교하여 감소하였고 (p<0.05) 이들 염증성 시토카인의 농도의 변화는 NF-κB의 농도의 변화와 상관 관계를 보였다 (p<0.01). 급성폐손상 지수는 EP+LPS군 및 LPS+EP군에서 LPS군과 비교하여 낮았고 (p<0.05) MPO활성은 EP+LPS군에서 LPS군에 비해 낮았다 (p<0.05). 결론: EP는 LPS로 인한 급성폐손상에 있어서 예방 및 치료 효과가 있는 것으로 판단된다. Background: Ethyl pyruvate (EP) is a derivative of pyruvate that has recently been identified by both various in vitro and in vivo studies to have antioxidant and anti-inflammatory effects. The aim of this study was to determine the effect of EP on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods: 5 weeks old, male BALB/c mice were used. ALI was induced by an intratracheal instillation of LPS 0.5㎎/㎏/50μL of saline. The mice were divided into the control, LPS, EP+LPS, and LPS+EP groups. In the control group, balanced salt solution was injected intraperitoneally 30 minutes before or 9 hours after the intratracheal instillation of saline. In the LPS group, a balanced salt solution was also injected intraperitoneally 30 minutes before or 9 hours after instillation the LPS. In the EP+LPS group, 40㎎/㎏ of EP was injected 30 minutes before LPS instillation. In the LPS+EP group, 40㎎/㎏ of EP was injected 9 hours after LPS instillation. The TNF-α and IL-6 concentrations in the bronchoalveolar lavage fluid (BALF), and that of NF-kB in the lung tissue were measured in the control, LPS and EP+LPS groups at 6 hours after instillation of saline or LPS, and the ALI score and myeloperoxidase (MPO) activity were measured in all four groups 24 and 48 hours after LPS instillation, respectively. Results: The TNF-α and IL-6 concentrations were significantly lower in the EP+LPS group than in the LPS group (p<0.05). The changes in the concentration of these inflammatory cytokines were strongly correlated with that of NF-κB (p<0.01). The ALI scores were significantly lower in the EP+LPS and LPS+EP groups compared with the LPS group (p<0.05). In the EP+LPS group, the MPO activity was significantly lower than the LPS group (p=0.019). Conclusion: EP, either administered before or after LPS instillation, has protective effects against the pathogenesis of LPS-induced ALI. EP has potential theurapeutic effects on LPS-induced ALI. (Tuberc Respir Dis 2006; 61: 374-383)

Serum Reactive Oxygen Species Modulator 1 as a Novel Predictive Biomarker for Resected Lung Adenocarcinoma

( Seung Hyeun Lee ),( In Kyung Hwang ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-

Purpose Reactive oxygen species modulator 1 (Romo1) is a key regulator of intracellular reactive oxygen species production. Studies have reported that Romo1 overexpression in tumor tissues is associated with a poor response to chemotherapy and early recurrence after surgical resection in patients with non-small cell lung cancer. However, the predictive value of serum Romo1 levels remains unclear. Methods We measured preoperative baseline serum Romo1 and carcinoembryonic antigen (CEA) levels in samples obtained from patients who underwent surgical resection of lung adenocarcinoma from August 2016 to March 2020. Univariate and multivariate analyses were used to determine serum Romo1 level is associated with disease-free survival (DFS). Results A total of 77 serum samples were eligible for the analysis. Using the cutoff value of 866 pg/mL, patients were categorized into low (n=42, 54.4%) and high (n=35, 45.4%) serum Romo1 groups. Survival analysis showed that the median DFS was significantly shorter in the high Romo1 group than in the low Romo1 group (25.5 months vs. not reached [NR], p=0.0017). Moreover, the median DFS was significantly shorter in the high CEA (>2.9 ng/mL) than in the low CEA group (34.1 months vs. NR, p=0.0251). Multivariate analyses showed that both high serum Romo1 and CEA levels were independently associated with poor DFS (hazard ratio [HR]=4.19, 95% confidence interval [CI]: 1.42-12.37, and HR=4.23, 95% CI: 1.23-8.58, respectively). Combined analysis of these two biomarkers showed that the HR for DFS was increased to 4.58 (95% CI 1.13-13.27). Conclusions Elevated serum Romo1 levels were significantly associated with early recurrence in patients who underwent surgical resection of lung adenocarcinoma. The serum Romo1 level may serve as a promising prognostic biomarker to predict clinical outcomes in this patient population.

Chemotherapy for Lung Cancer in the Era of Personalized Medicine

Lee, Seung Hyeun The Korean Academy of Tuberculosis and Respiratory 2019 Tuberculosis and Respiratory Diseases Vol.82 No.3

Although recent advances in molecular targeted therapy and immuno-oncology have revolutionized the landscape of lung cancer therapeutics, cytotoxic chemotherapy remains an essential component of lung cancer treatment. Extensive evidence has demonstrated the clinical benefit of chemotherapy, either alone or in combination with other treatment modalities, on survival and quality of life of patients with early and advanced lung cancer. Combinational approaches with other classes of anti-neoplastic agents and new drug-delivery systems have revealed promising data and are areas of active investigation. Chemotherapy is recommended as a standard of care in patients that have progressed after tyrosine kinase inhibitors or immune checkpoint inhibitors. Chemotherapy remains the fundamental means of lung cancer management and keeps expanding its clinical implication. This review will discuss the current position and future role of chemotherapy, and specific consideration for its clinical application in the era of precision medicine.

High Tumor Mutation Burden Predicts Unfavorable Clinical Outcomes in EGFR-mutated Lung Adenocarcinoma Treated with Targeted Therapy

( Seung Hyeun Lee ),( Dong Won Park ),( Ji-youn Sung ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-

Purpose Although high tumor mutation burden (TMB) has shown an association with benefit from immune checkpoint blockade therapies, its implications in lung cancer patients with driver mutations are still unclear. The objective of this study is to determine the association between TMB and treatment outcome in epidermal growth factor receptor (EGFR)-mutated lung cancer treated with tyrosine kinase inhibitors (TKIs). Methods We evaluated TMB in EGFR-mutant, lung adenocarcinoma patients who received first-line EGFR-TKIs. TMB was estimated by next-generation sequencing with a cancer gene panel (Ion AmpliSeq Comprehensive Cancer Panel). We compared the progression-free survival (PFS), overall survival (OS), and frequency of secondary T790M mutation according to different TMB groups. Results Among the 131 patients who were treated with EGFR-TKIs, a total of 88 patients were eligible for the analysis. At the cutoff of 2.53/Mbp, 36 (40.9%) and 52 (59.1%) patients were classified into the low and high TMB groups, respectively. The TMB level was significantly associated with liver metastasis. The median PFS (12.05 months vs 15.5 months, p=0.0205) and OS (21.9 months vs 37.1 months, p= 0.0008) was significantly shorter in the high TMB group. In multivariate analysis, high TMB was independently associated with a shorter PFS (hazard ratio [HR] = 1.64, p = 0.0240) and shorter OS (HR = 2.05, p = 0.0397) compared with low TMB. In addition, the frequencies of secondary T790M mutation after TKI failure were significantly lower in the high TMB group (21.9% vs 47.4%, p= 0.0266). Conclusion High TMB was associated with unfavorable clinical outcome and less development of secondary T790M mutation, suggesting a distinct subgroup warranting active surveillance and tailored therapeutic approach.