Subgroup analysis of a phase 2/3 study of rurioctocog alfa pegol in patients with severe hemophilia A: efficacy and safety in previously treated Korean patients

Chur Woo You,백희조,Sang Kyu Park,박영실,Ho-Jin Shin,Werner Engl,Srilatha Tangada 대한혈액학회 2019 Blood Research Vol.54 No.3

BackgroundThe efficacy and safety of extended half-life, full-length, pegylated recombinant factor VIII rurioctocog alfa pegol [BAX 855, ADYNOVATE (USA)/ADYNOVI (Europe); Baxalta US Inc., a Takeda company, Lexington, MA, USA] was investigated in previously treated Korean patients with severe hemophilia A (HA).MethodsA post hoc data analysis from the international, multicenter, phase 2/3 PROLONG-ATE study of rurioctocog alfa pegol in patients with severe HA (NCT01736475) determined annualized bleeding rates (ABRs) and rates of adverse events (AEs) in Korean patients treated in this study.ResultsAll 10 enrolled Korean patients receiving rurioctocog alfa pegol (9 prophylaxis, 1 on-de-mand) completed the study [median (range) age, 28.0 (12‒50) yr; weight, 64.8 (45‒90) kg; 8 patients had ≥1 target joint at screening]. Median (range) ABR was 1.9 (0.0‒14.5) for patients on prophylaxis and 62.2 for the patient receiving on-demand treatment. The hemostatic efficacy of rurioctocog alfa pegol was rated “excellent” or “good” and only single infusions were required per bleeding episode. ABRs improved in most patients compared with prestudy values. No dose adjustments were required for prophylaxis, and the dosing frequency was reduced in 8 patients, compared with their previous prophy-laxis regimen. No serious AEs were reported; all 9 nonserious AEs (in 3 patients) were mild in severity and unrelated to the study treatment.ConclusionThis post hoc analysis of a small group of Korean patients with severe HA indicated that rurioctocog alfa pegol was effective, and no serious AEs were observed. For most patients, the dosing frequency was also reduced compared with their previous regimen.

A Case of Acute Encephalopathy in Respiratory Syncytial Virus Sepsis Syndrome

유철우(Chur Woo You),이수진(Soo Jin Lee),곡진진(Chen Chen Chu),김현정(Hyun Jung Kim),김승연(Seung Yeon Kim),남지우(Ji woo Nam),김존수(Jon Soo Kim),강주형(Ju Hyung Kang) 대한소아신경학회 2015 대한소아신경학회지 Vol.23 No.2

호흡기 세포융합 바이러스(RSV)는 소아에서 급성 호흡기 감염을 일으키는 가장 흔한 바이러스중 하나로 대부분 경한 호흡기 증상을 일으킨 후 호전 보이지만 1%에서는 중증의 임상경과를 보인다. 중증 RSV 감염에서 호흡기 증상과 동반된 호흡기외 증상이 더 자주 보고되고 있으나 이와 관련된 뇌증에 대한 보고는 많이 알려지지 않았다. 저자들은 미숙아로 출생하여 기관지폐이형성증을 기저질환으로 갖고 있는 8 개월 남아가 RSV에 감염되어 급성 뇌증을 일으켰고 이후 패혈증 증후군으로 진행되었다가 면역글로불린 치료 후 회복되었지만 신경학적 후유증이 남게 된 증례를 보고하고자 한다. Respiratory syncytial virus (RSV) is the most common and important etiologic agent of early childhood respiratory infections, resulting in significant morbidity and mor­tality. Extrapulmonary manifestations combined with respiratory symptoms are being reported more frequently in severe RSV infection, but the encephalopathy as­sociated with this infection is not well recognized. RSV encephalopathy was present with impaired consciousness, cyanosis, sucking disorder preceding convulsive sei­zures. The authors describe the symptoms and outcomes of an 8­month­old boy, who present with acute encephalopathy and had prematurity, bronchopulmonary dysplasia as comorbidities. The boy developed sepsis syndrome, characterized by hypotension, hepatic and renal dysfunctions, later found to be infected with RSV. He finally recovered after treatment with immumoglobulin and supportive care but required portable mechanical ventilation, nasogastric tube feeding, and anticonvul­sant medication at discharge.

The prevalence and risk factors of inhibitor development of FVIII in previously treated patients with hemophilia A

Ju Young Kim,Chur Woo You 대한혈액학회 2019 Blood Research Vol.54 No.3

BackgroundRisk factors for the development of inhibitors in previously untreated patients (PUPs) have been reported; this is not the case in previously treated patients (PTPs) owing to fewer studies. Risk factors may differ for the development of PTP versus PUP inhibitors. We aimed to identify risk factors for PTP inhibitor development.MethodsParticipants were patients at a hemophilia treatment center in Korea with current or past history of factor VIII or factor IX alloantibodies. Observed inhibitors were classified as PUP or PTP inhibitors based on the cumulative number of exposure days. We compared the type and severity of hemophilia, mutation type, and family history of inhibitor between PUPs and PTPs. Events within 3 months before the first inhibitor detection, such as change of the factor concentrate used, short-term high exposure or continuous infusion of factor concentrate, history of surgery, infection, diagnosis of cancer, use of immunosuppressive or immunomodulator agents, and vaccination were compared between PUPs and PTPs.ResultsWe observed 5 PUP inhibitors and 5 PTP inhibitors in 115 patients with hemophilia A. Events that might be related to the development of inhibitors within 3 months prior to the first inhibitor detection were observed in all 5 PTPs. On the contrary, no such events were observed in any PUPs. The observed events included a change in the factor concen-trate used, subsequent chemotherapy, and short-term high exposure to factor concen-trates for controlling hemorrhage and surgeries.ConclusionOur results suggest a greater role of nongenetic factors in PTP inhibitor development.

Clinical analysis of hospitalized patients with hemophilia A: single-hemophilia treatment center experience in Korea over 10 years

Ju Young Kim,Se Jin Park,Chur Woo You 대한혈액학회 2021 Blood Research Vol.56 No.3

Background There is lack of data on admitted hemophilia patients in Korea. For this reason, this study was intended to analyze the hospitalization data of hemophilia patients in a regional Hemophilia Treatment Center (HTC) for the first time in Korea. Methods In this retrospective study, we surveyed hospitalized patients with Hemophilia A (HA) in a HTC for 14 years. Medical records of these hemophiliacs were reviewed and data regarding demographic characteristics, cause of admissions and their outcomes in each patient were obtained. In addition, the data of admitted days, type and amount of Coagulation factor concentrate (CFC) used, treatments other than CFC infusion during the admission days were also obtained from the medical record of each patient. Results A total 107 patients with hemophilia A were admitted during 14 years. Annual rate of admission of patients with HA was 8%. Mean age on admission was 29.63±19.51 years old and mean admission days were 11.28±5.46 days. Most admissions were occurred in severe and moderate hemophilia patients. The most common cause of admission was bleed control followed by surgery and other reasons. With modified WFH CFC supplementation guideline, all the bleeds were successfully controlled and all surgeries were also successfully conducted with less total CFC consumption compared to the consumed dose of other reports. Conclusion These results suggest that it is necessary to develop more specified regimens different from WFH guidelines of CFC supplementation for admitted Korean patients with hemophilia A.

Effects of coagulation factor concentrate prophylaxis in moderate and severe hemophilia A patients at a single hemophilia center in Korea

Moon, Byung Suk,Choi, Jun Seok,You, Chur Woo The Korean Pediatric Society 2013 Clinical and Experimental Pediatrics (CEP) Vol.56 No.7

Purpose: The aim of this study was to investigate prophylactic treatment effects in Korean patients with severe hemophilia A. Methods: A prospective study of 32 severe hemophilia A patients was conducted with the approval of the Institutional Review Board at the Eulji University Hospital. Two patients received primary prophylaxis; whereas, the other 30 patients were divided into 2 groups-secondary prophylaxis (n=15) and on-demand (n=15)-on the basis of their consent for secondary prophylaxis. A 20-25 IU/kg dose of factor VIII concentrate was administered to the primary and secondary prophylaxis group patients every 3 days for 1 year. The prophylactic effect was evaluated by observing changes in the Pettersson scores, annual number of total and joint bleeds, and factor VIII consumption for 1 year. Results: No moderate or severe bleeding was observed, and the Pettersson scores remained unchanged during the prophylaxis period in the patients who received primary prophylactic treatment. After the treatment was changed from on-demand to secondary prophylaxis, the annual number of total and joint bleeds in the secondary prophylaxis group decreased by $64.4%{\pm}13.0%$ and $70.0%{\pm}15.2%$, respectively. The average increase in Pettersson scores within 1 year was $0.5{\pm}0.8$ and $1.3{\pm}1.1$ in the secondary prophylaxis and on-demand groups, respectively. Prophylactic effects were also observed in patients >17 years who had nearly the same initial Pettersson scores. Conclusion: Intermediate-dose prophylactic treatment may delay hemarthropathy progression and prevent its occurrence in Korean severe hemophilia A patients.

Dual Energy X-ray Absorptiometry를 이용한 소아들의 골밀도에 대한 연구

김선용,신손문,유철우,박용훈 영남대학교 의과대학 1993 Yeungnam University Journal of Medicine Vol.10 No.2

Dual energy x-ray absorptiometry(DEXA)를 이용하여 골밀도에 영향을 줄 인자가 없는 소아 80명을 대상으로 제2-4요추에서 골밀도를 측정하여 연령군과 Tanner stage의 변화에 따른 골밀도의 변화를 연구하고 골밀도와 연령, 체중, 신장, 골연령, 성별, 혈청칼슘, 무기인, 부갑상선호르몬과 Alkaline phosphatase 등과의 상관관계를 알아본 결과, 골밀도는 연령(r=0.696), 체중(r=0.693), 신장(r=0.717), 골연령(r=0.690) 및 Tanner stage(r=0.636) 와 유의한 상관관계가 있었으나(r>0.6) 골대사의 지표인 혈청 칼슘, 무기인, 부갑상선 호르몬 ALP나 성별과는 유의한 상관관계가 없었으며, 특히 남, 여 그리고 전체 환아 각각의 경우에서 연령, 체중, 신장과 골밀도의 직선적 상관관계(남아 : 연령 y=0.4223+0.0289x, 체중 y=0.3879+0.0087x, 신장 y=0.1362+0.0042x 여아 : 연령 y=0.3731+0.0494x, 체중 y=0.3206+0.014x, 신장 y=0.0782+0.0070x 전체 : 연령 y=0.4113+0.0354x, 체중 y=0.3690+0.0107x, 신장 y=0.0628+0.0051x)가 있었다. 연구대상 소아를 4개의 연령군(1군 : 2개월-1세미만, 2군 : 1세이상-5세이하, 3군 : 6세이상-10세이하, 4군 : 11세이상-15세이하)로 나누어 조사한 결과 연령군에 따른 골밀도(g/㎠)의 증가는 1군(BMD:0.335 ±0.175)과 2군(BMD:0.627 ±0.200) 그리고 3군(BMD:0.714 ±0.1896)과 4군(BMD:0.873 ±0.163)에서 유의하게 증가하였으나(p<0.05), 2군과 3군사이에서는 유의한 골밀도의 증가를 관찰할 수 없었으며 남녀간 골밀도의 차이는 없었다(p<0.05). 또한 Tanner stage의 발달에 따라서는 골밀도(g/㎠)는 Tanner stage 1에서는 0.547 ±0.234, Tanner stage 2에서는 0.783 ±0.136, Tanner stage 3에서는 0.998 ±0.080으로서 모든 단계에서 유의하게 증가하였다(p<0.05). 이상의 결과에 의하면 DEXA로 측정한 골밀도는 연령, 체중과 신장 등의 증가와 유의한 상관관계가 있고 이들은 성장 속도가 빠른 연령에서 유의하게 증가하였으며 특히 성적 성숙도의 발달에 따라 유의하게 증가하였다. The bone mineral density(BMD) of the lumbar spine (L2-L4) was measured by using dual energy x-ray absorptiometry(Norland XR26 DEXA) in 80 children aged between 2months and 15years (group 1 : 2month-1years, group 2 : 1year-5years, group 3 ; 6years-10years, group 4 : 11years-15years). The correlation coefficient of BMD with age, body weight, height and Tanner stage were 0.696, 0.693, 0.717 and 0.636 respectively. There were sigificant difference in BMD(g/㎠) between group 1(BMD:0.335 ±0.175) and group 2(BMD:0.627 ±0.200), and group 3(BMD:0.714 ±0.1896) and group 4(BMD:0.873 ±0.163) (p<0.05). There was no significant difference of BMD between boys and girls(p<0.05). BMD also increased significantly with development of Tanner stages(Tanner stage 1 : 0.547 ±0.234, Tanner stage 2 : 0.783 ±0.136, Tanner stage 3 : 0.998 ±0.080) (p<0.05). These data indicate that the BMD was correlated with age, body weight, height and Tanner stage significantly and BMD increased significantly during growth spurt occured in 1 to 4years of age and puberty.

A pediatric case of idiopathic Harlequin syndrome

Ju Young Kim,Moon Souk Lee,Seung-Yeon Kim,Hyun Jung Kim,Soo Jin Lee,Chur Woo You,Jon Soo Kim,Ju Hyung Kang 대한소아청소년과학회 2016 Clinical and Experimental Pediatrics (CEP) Vol.59 No.no.sup1

Harlequin syndrome, which is a rare disorder caused by dysfunction of the autonomic system, manifests as asymmetric facial flushing and sweating in response to heat, exercise, or emotional factors. The syndrome may be primary (idiopathic) with a benign course, or can occur secondary to structural abnormalities or iatrogenic factors. The precise mechanism underlying idiopathic harlequin syndrome remains unclear. Here, we describe a case of a 6-year-old boy who reported left hemifacial flushing and sweating after exercise. He had an unremarkable birth history and no significant medical history. Complete ophthalmological and neurological examinations were performed, and no other abnormalities were identified. Magnetic resonance imaging was performed to exclude lesions of the cerebrum and cervicothoracic spinal cord, and no abnormalities were noted. His final diagnosis was classic idiopathic harlequin syndrome. Herein, we report the first pediatric case of idiopathic harlequin syndrome in Korea.

A pediatric case of idiopathic Harlequin syndrome

Kim, Ju Young,Lee, Moon Souk,Kim, Seung Yeon,Kim, Hyun Jung,Lee, Soo Jin,You, Chur Woo,Kim, Jon Soo,Kang, Ju Hyung The Korean Pediatric Society 2016 Clinical and Experimental Pediatrics (CEP) Vol.59 No.no.sup1

Harlequin syndrome, which is a rare disorder caused by dysfunction of the autonomic system, manifests as asymmetric facial flushing and sweating in response to heat, exercise, or emotional factors. The syndrome may be primary (idiopathic) with a benign course, or can occur secondary to structural abnormalities or iatrogenic factors. The precise mechanism underlying idiopathic harlequin syndrome remains unclear. Here, we describe a case of a 6-year-old boy who reported left hemifacial flushing and sweating after exercise. He had an unremarkable birth history and no significant medical history. Complete ophthalmological and neurological examinations were performed, and no other abnormalities were identified. Magnetic resonance imaging was performed to exclude lesions of the cerebrum and cervicothoracic spinal cord, and no abnormalities were noted. His final diagnosis was classic idiopathic harlequin syndrome. Herein, we report the first pediatric case of idiopathic harlequin syndrome in Korea.

인플루엔자 감염으로 유발된 경련의 임상적 특징

박영미(Young Mi Park),이효은(Hyo Eun Lee),김승연(Seung Yeon Kim),김현정(Hyun Jung Kim),강주형(Ju Hyung Kang),이수진(Soo Jin Lee),유철우(Chur Woo You),김존수(Jon Soo Kim) 대한소아신경학회 2015 대한소아신경학회지 Vol.23 No.3

목적: 인플루엔자는 대표적인 급성 호흡기질환으로 소아 열성경련의 흔한 원인으로 알려져 있다. 경련은 인플루엔자 감염과 관련된 가장 흔한 중추신경계 증상이며, 본 연구에서는 인플루엔자 감염과 연 관된 경련의 발생 양상과 임상증상을 분석하여 이에 대한 이해를 높이고자 한다. 방법: 2013년 12 월부터 2015년 4 월까지 을지대학교병원 소아청 소년과 외래 및 소아응급실을 방문한 만 18세 이하의 환자 중 비인두 도말 검체에서 시행한 신속항원검사를 통해 인플루엔자 감염으로 진 단된 환자를 대상으로 하였다. 의무기록의 후향적 조사를 통해 나이, 성별, 확인된 인플루엔자 바이러스 항원형, 경련발생 유무 및 양상, 과 거 열성경련 병력, 기저 신경학적 질환, 치료 및 예후 등을 확인하였다. 결과: 인플루엔자로 확인된 소아청소년은 총 290명이었고 Season 2014에 153명, Season 2015에 137명으로 비슷한 발병율을 보였다. 전체 환자의 평균 나이는 5.1세였고, A형 인플루엔자가 211명(72.8%) 으로 인플루엔자 감염의 주요 항원형이었다. 30명(10.3%)에서 인플루엔자 감염기간 동안 경련이 발생하였고 평균 나이는 4.8세였다. 이중 33.3%가 6세 이후에 발생하였고, 항원형에 따른 경련발생율(A:B= 10.4%:10.1%)의 차이는 없었다. 과거 열성경련의 과거력이 있는 경우 경련이 발생한 군에서 56.7%로 유의하게 호발하였고, 기저 신경학적 질환(뇌성마비, 뇌전증 등)이 있었던 환자들에게서 10.0%로 경련이 더 발생하였다. 경련은 전신발작형태(83.3%)로 나타났으며, 대부분 처 음 발열이 있은 후 12시간이내에 경련이 발생하였고(70.0%), 5분이내 에 종료되었다(93.3%). 일부 뇌파 및 두부 MRI검사를 시행한 환자 모 두 정상소견이었다. 추가적인 항경련제를 투여받은 환자는 없었으며, 모든 환자는 발열이 조절된 이후 신경학적 합병증 없이 퇴원하였다. 결론: 소아청소년기 전 연령층에서 인플루엔자 감염과 연관된 경련 이 드물지 않게 발생하며 주로 단순열성경련 형태로 대부분 양호한 예후를 갖게 된다. 하지만 급성 뇌증과 같은 다른 신경증상이 동반되 는 경우 주의를 기울여야 할 것이다. Purpose: Seizures are the most frequently reported neurologic complication during an influenza epidemic. Even older than 5 years, influenza-associated seizure increa-ses significantly in children. This study sought to better understand the risks and outcomes of seizures associated with epidemic influenza in the pediatric population. Method: We retrospectively reviewed the medical charts of children with laboratory-confirmed influenza between December 2013 and April 2015. Data analyzed included patient’s demographics, clinical presentation, radiological and electroencephalographic findings, management and prognosis. Results: A total of 290 children (male 168, female 122) were identified as having labora-tory-confirmed influenza A (211 of 290; 72.8%) or B (79 of 290; 27.2%). The mean age was 4.6 years (range, 0.1-17.2 years). Among them, 30 (10.3%) patients had seizures at a median age 4.8 years (range, 0.7-15.0 years), including 10 (33.3%) patients older than 5 years. All patients had fever and 17 (56.7%) patients had history of febrile seizure. Mostly, they showed generalized seizure (25 of 30; 83.3%) and prolonged seizure of less than 5 minutes (28 of 30; 93.3%). Sixteen (53.3%) underwent Electroencephalogram (EEG) and revealed normal finding in all patients. Brain Magnetic resonance imaging(MRI) was performed in 5 (16.7%) patients without abnormality. Four patients (13.3%) had more seizures during febrile illness but no need to treat with intravenous antiepileptic drugs. All patients discharged to home without complication. Conclusion: Although most patients with influenza-associated seizure had benign clinical course, we should be aware of occurrence in all age group of childhood as well as beyond the typical age at which febrile seizures.