1.The Korean Society for Neuro-Oncology (KSNO) Guideline for Glioblastomas: Version 2018.01
Young Zoon KIM ; Chae Yong KIM ; Jaejoon LIM ; Kyoung Su SUNG ; Jihae LEE ; Hyuk Jin OH ; Seok Gu KANG ; Shin Hyuk KANG ; Doo Sik KONG ; Sung Hwan KIM ; Se Hyuk KIM ; Se Hoon KIM ; Yu Jung KIM ; Eui Hyun KIM ; In Ah KIM ; Ho Sung KIM ; Tae Hoon ROH ; Jae Sung PARK ; Hyun Jin PARK ; Sang Woo SONG ; Seung Ho YANG ; Wan Soo YOON ; Hong In YOON ; Soon Tae LEE ; Sea Won LEE ; Youn Soo LEE ; Chan Woo WEE ; Jong Hee CHANG ; Tae Young JUNG ; Hye Lim JUNG ; Jae Ho CHO ; Seung Hong CHOI ; Hyoung Soo CHOI ; Je Beom HONG ; Do Hoon LIM ; Dong Sup CHUNG ;
Brain Tumor Research and Treatment 2019;7(1):1-9
BACKGROUND: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. RESULTS: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment. CONCLUSION: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient.
Brain
;
Central Nervous System
;
Chemoradiotherapy
;
Diagnosis
;
Drug Therapy
;
Glioblastoma
;
Humans
;
Korea
;
Radiotherapy
2.The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade II Cerebral Gliomas in Adults: Version 2019.01
Young Zoon KIM ; Chae Yong KIM ; Chan Woo WEE ; Tae Hoon ROH ; Je Beom HONG ; Hyuk Jin OH ; Seok Gu KANG ; Shin Hyuk KANG ; Doo Sik KONG ; Sung Hwan KIM ; Se Hyuk KIM ; Se Hoon KIM ; Yu Jung KIM ; Eui Hyun KIM ; In Ah KIM ; Ho Sung KIM ; Jae Sung PARK ; Hyun Jin PARK ; Sang Woo SONG ; Kyoung Su SUNG ; Seung Ho YANG ; Wan Soo YOON ; Hong In YOON ; Jihae LEE ; Soon Tae LEE ; Sea Won LEE ; Youn Soo LEE ; Jaejoon LIM ; Jong Hee CHANG ; Tae Young JUNG ; Hye Lim JUNG ; Jae Ho CHO ; Seung Hong CHOI ; Hyoung Soo CHOI ; Do Hoon LIM ; Dong Sup CHUNG ;
Brain Tumor Research and Treatment 2019;7(2):74-84
BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults. RESULTS: Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase (IDH)-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, IDH-mutant and oligodendroglioma (IDH-mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group. CONCLUSION: The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients.
Adult
;
Astrocytoma
;
Brain
;
Central Nervous System
;
Drug Therapy
;
Drug Therapy, Combination
;
Follow-Up Studies
;
Glioblastoma
;
Glioma
;
Humans
;
Isocitrate Dehydrogenase
;
Korea
;
Oligodendroglioma
;
Radiotherapy
;
World Health Organization
3.The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade III Cerebral Gliomas in Adults: Version 2019.01
Young Zoon KIM ; Chae Yong KIM ; Jaejoon LIM ; Kyoung Su SUNG ; Jihae LEE ; Hyuk Jin OH ; Seok Gu KANG ; Shin Hyuk KANG ; Doo Sik KONG ; Sung Hwan KIM ; Se Hyuk KIM ; Se Hoon KIM ; Yu Jung KIM ; Eui Hyun KIM ; In Ah KIM ; Ho Sung KIM ; Tae Hoon ROH ; Jae Sung PARK ; Hyun Jin PARK ; Sang Woo SONG ; Seung Ho YANG ; Wan Soo YOON ; Hong In YOON ; Soon Tae LEE ; Sea Won LEE ; Youn Soo LEE ; Chan Woo WEE ; Jong Hee CHANG ; Tae Young JUNG ; Hye Lim JUNG ; Jae Ho CHO ; Seung Hong CHOI ; Hyoung Soo CHOI ; Je Beom HONG ; Do Hoon LIM ; Dong Sup CHUNG ;
Brain Tumor Research and Treatment 2019;7(2):63-73
BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea in the past. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, developed the guideline for glioblastoma successfully and published it in Brain Tumor Research and Treatment, the official journal of KSNO, in April 2019. Recently, the KSNO guideline for World Health Organization (WHO) grade III cerebral glioma in adults has been established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searches in PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords. Scope of the disease was confined to cerebral anaplastic astrocytoma and oligodendroglioma in adults. RESULTS: Whenever radiological feature suggests high grade glioma, maximal safe resection if feasible is globally recommended. After molecular and histological examinations, patients with anaplastic astrocytoma, isocitrate dehydrogenase (IDH)-mutant should be primary treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy whereas those with anaplastic astrocytoma, NOS, and anaplastic astrocytoma, IDH-wildtype should be treated following the protocol for glioblastomas. In terms of anaplastic oligodendroglioma, IDH-mutant and 1p19q-codeletion, and anaplastic oligodendroglioma, NOS should be primary treated by standard brain radiotherapy and neoadjuvant or adjuvant PCV (procarbazine, lomustine, and vincristine) combination chemotherapy. CONCLUSION: The KSNO's guideline recommends that WHO grade III cerebral glioma of adults should be treated by maximal safe resection if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors.
Adult
;
Astrocytoma
;
Brain
;
Brain Neoplasms
;
Central Nervous System
;
Drug Therapy
;
Drug Therapy, Combination
;
Glioblastoma
;
Glioma
;
Humans
;
Isocitrate Dehydrogenase
;
Korea
;
Lomustine
;
Oligodendroglioma
;
Radiotherapy
;
World Health Organization
4.Single Incision Laparoscopic Appendectomy for Management of Complicated Appendicitis: Comparison between Single-Incision and Conventional.
Yoon Jung OH ; Nak Song SUNG ; Won Jun CHOI ; Dae Sung YOON ; In Seok CHOI ; Sang Eok LEE ; Ju Ik MOON ; Seong Uk KWON ; Si Min PARK ; In Eui BAE
Journal of Minimally Invasive Surgery 2018;21(4):148-153
PURPOSE: Single incision laparoscopic appendectomy (SILA) is a widely used surgical procedure for treatment of appendicitis with better cosmesis. However, many surgeons generally tend to choose conventional multiport laparoscopic appendectomy regarding with complicated appendicitis. The aim of this study is to demonstrate the safety and feasibility of SILA for treatment of complicated appendicitis by comparison with 3-ports conventional laparoscopic appendectomy (CLA). METHODS: Retrospective chart review of patients diagnosed appendicitis at single hospital during January 2015 to May 2017 collected 500 patients. Among 134 patients with complicated appendicitis, we compared outcomes for 29 patients who got SILA and 105 patients who got CLA. RESULTS: 179 and 321 patients were treated by SILA and CLA, respectively. 134 (26.8%) patients were treated for complicated appendicitis, 29 patients by SILA and 105 patients by CLA, respectively. There was no case converted to open or added additional trocar in both groups. There were no differences in demographics with regard to age, sex, body mass index (BMI), and American society of anesthesiologists (ASA) scores. There was no difference in mean operating time (58.97±18.53 (SILA) vs. 57.57±21.48 (CLA), p=0.751). The drain insertion rate (6.9% vs 37.1%, p=0.001) and the length of hospital stay (2.76±1.41 vs. 3.97±2.97, p=0.035) were lower in SILA group with significance. There was no significant difference in the rate of surgical site infection (6.9% vs. 6.7%, p=1.000). CONCLUSION: This study demonstrates that SILA is a feasible and safe procedure for treatment of complicated appendicitis.
Appendectomy*
;
Appendicitis*
;
Body Mass Index
;
Demography
;
Humans
;
Length of Stay
;
Retrospective Studies
;
Surgeons
;
Surgical Instruments
;
Surgical Wound Infection
5.Associates and Prognosis of Giant Left Atrium; Single Center Experience.
Hyoeun KIM ; Young Ah PARK ; Sung Min CHOI ; Hyemoon CHUNG ; Jong Youn KIM ; Pil Ki MIN ; Young Won YOON ; Byoung Kwon LEE ; Bum Kee HONG ; Se Joong RIM ; Hyuck Moon KWON ; Eui Young CHOI
Journal of Cardiovascular Ultrasound 2017;25(3):84-90
BACKGROUND: Left atrial (LA) remodeling develops as a result of longstanding pressure overload. However, determinants and clinical outcome of excessive remodeling, so called giant left atrium (GLA), are not clear. METHODS: Clinical characteristics of patients with GLA (antero-posterior diameter higher than 65 mm), including echo-Doppler parameters, and follow-up clinical outcomes from a tertiary referral hospital were investigated. RESULTS: Among 68519 consecutive primary patients who underwent echocardiography over a period of 10 years, data from 163 GLA cases (0.24%) were analyzed. Main causes were significant rheumatic mitral stenosis (n = 58, 36%); other causes comprised significant rheumatic mitral regurgitation (MR; n = 10, 6%), mitral valve (MV) prolapse or congenital mitral valvular disease (MVD) (n = 20, 12%), and functional MR (n = 25, 15%). However, mild rheumatic MV disease (n = 4, 3%) or left ventricular (LV) systolic or diastolic dysfunction without significant MR (n = 46, 28%) were also causes of GLA. During median follow-up of 22 months, 42 cases (26%) underwent composite events. MV surgery was related to lower rate of composite events. In multivariate analysis, MV surgery, elevated pulmonary arterial systolic pressure, and increased LA volume index were independent predictors of future events (p < 0.05) regardless of underlying diseases or history of MV surgery. CONCLUSION: Although rheumatic MVD with atrial fibrillation is the main contributor to GLA, longstanding atrial fibrillation with LV dysfunction but without MVD also could be related to GLA. Even in GLA state, accurate measurement of LA volume is crucial for risk stratification for future events, regardless of underlying disease.
Atrial Fibrillation
;
Blood Pressure
;
Echocardiography
;
Follow-Up Studies
;
Heart Atria*
;
Humans
;
Mitral Valve
;
Mitral Valve Insufficiency
;
Mitral Valve Stenosis
;
Multivariate Analysis
;
Prognosis*
;
Prolapse
;
Tertiary Care Centers
6.Effects of Estradiol on the Paracrine Regulator Expression of In Vitro Maturated Murine Ovarian Follicles.
Yong Jin KIM ; Kyung Eui PARK ; Yoon Young KIM ; Hoon KIM ; Seung Yup KU ; Chang Suk SUH ; Seok Hyun KIM ; Young Min CHOI
Tissue Engineering and Regenerative Medicine 2017;14(1):31-28
The preservation of female germ cells is important in the individuals with ovarian dysfunction and failure. For this purpose, ovarian follicle in vitro maturation (OFIVM) is an important technology for the retrieval of mature oocytes. In the in vivo follicular development, paracrine factors such as angiotensin (AT) and anti-Müllerian hormone (AMH) play important roles. We attempted to add estrogen during the OFIVM and to assess their expression on the follicular cells. The ovaries and pre-antral follicles were collected from 13-day C57BL/6 mice and cultured in vitro with estradiol (E₂) treatment for up to two weeks. In the whole ovaries, the expression of AT II was decreased and the expression of AMH was similar between control and E₂-treated ovaries after in vitro culture. Although there was no difference in the survival, ovulation, maturation and fertilization rates between control and E₂-treated groups, the expression of AT II in the follicular cells was down-regulated after E₂ treatment at mRNA level, and AMH showed similar expression. In conclusion, adding E₂ in OFIVM may regulate paracrine factors and their receptors that are related to follicular development. Further investigations are necessary to elucidate the roles of various sex hormones in the regulation of AT and AMH expression during the OFIVM.
Angiotensins
;
Animals
;
Estradiol*
;
Estrogens
;
Female
;
Fertilization
;
Germ Cells
;
Gonadal Steroid Hormones
;
Humans
;
In Vitro Techniques*
;
Mice
;
Oocytes
;
Ovarian Follicle*
;
Ovary
;
Ovulation
;
RNA, Messenger
7.Analgesic Effect of Hippophae rhamnoides Extract in Orofacial Pain in Rats.
Yun Kyung KIM ; Ja Hyeong CHOI ; Hee Jin KIM ; Hyun Seo YOON ; Kyung Yae HYUN ; Min Kyung LEE
Journal of Dental Hygiene Science 2017;17(6):495-500
Hippophae rhamnoides L. (sea buckthorn) is a shrub wood that belongs to the bamboo tree family, and is rich in vitamin C, D, and E; it is referred to as a vitamin tree. It is mainly grown in the high mountains of Europe and Central Asia, and has been widely used in China and Russia as natural medicine. Recent studies have shown that it is effective in the treatment of cancer, liver diseases, cardiovascular diseases, and gastrointestinal diseases. However, results of studies on its effect on the regulation of pain are insufficient. In this study, we investigated the effect of sea buckthorn on the development and control of pain in two facial areas. The experimental animals included 7- to 8-week-old Sprague-Dawley rats (240~260 g). Formalin (5%), which is known as an inflammation inducer, was injected into the vibrissa pad or temporomandibular joints to induce orofacial acute pain. Rubbing or scraping of the region injected with formalin was regarded as a pain index, and the behavioral response was observed for 45 minutes after the injection. Sea buckthorn extract diluted to 150, 300 mg/kg (in 1 ml of distilled water) was orally administered 30 minutes prior to the acute pain. The facial pain behavior was effectively reduced in the 300 mg/kg group when compared to the control group (vehicle). Likewise, in an experiment in which formalin was injected into the temporomandibular joints, effective pain alleviation was confirmed at the same drug concentration. These results suggest that sea buckthorn extract may be useful in the development of therapeutic agents for acute inflammatory pain in the orofacial area and for controlling temporomandibular joint pain.
Acute Pain
;
Animals
;
Ascorbic Acid
;
Asia
;
Cardiovascular Diseases
;
China
;
Europe
;
Facial Pain*
;
Formaldehyde
;
Gastrointestinal Diseases
;
Hippophae*
;
Humans
;
Inflammation
;
Liver Neoplasms
;
Rats*
;
Rats, Sprague-Dawley
;
Russia
;
Temporomandibular Joint
;
Trees
;
Vitamins
;
Wood
8.Impact of early coronary angiography on the survival to discharge after out-of-hospital cardiac arrest.
Jikyoung SHIN ; Eunsil KO ; Won Chul CHA ; Tae Rim LEE ; Hee YOON ; Sung Yeon HWANG ; Tae Gun SHIN ; Min Seob SIM ; Ik Joon JO ; Keun Jeong SONG ; Joong Eui RHEE ; Yeon Kwon JEONG ; Jin Ho CHOI
Clinical and Experimental Emergency Medicine 2017;4(2):65-72
OBJECTIVE: Acute myocardial infarction is a major cause of out-of-hospital cardiac arrest (OHCA). Coronary angiography (CAG) enables diagnostic confirmation of coronary artery disease and subsequent revascularization, which might improve the prognosis of OHCA survivors. Non-randomized data has shown a favorable impact of CAG on prognosis for this population. However, the optimal timing of CAG has been debated. METHODS: The clinical outcomes of 607 OHCA patients registered in CAPTURES (Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance), a nationwide multicenter registry performed in 27 hospitals, were analyzed. Early CAG was defined as CAG performed within 24 hours of emergency department admission. The primary outcome was survival to discharge, with neurologically favorable status defined by cerebral performance category scores ≤2. RESULTS: Compared to patients without CAG (n=469), patients who underwent early CAG (n=138) were younger, more likely to be male, and more likely to have received bystander cardiopulmonary resuscitation, pre-hospital defibrillation, and revascularization (P<0.01 for all). Analysis of 115 propensity score-matched pairs showed that early CAG is associated with a 2.3-fold increase in survival to discharge with neurologically favorable status (P<0.001, all). Survival to discharge increased consistently according to the time interval between emergency department visit and CAG (P<0.05). CONCLUSION: Early CAG of OHCA patients was associated with better survival and favorable neurologic outcomes at discharge. However, there was no clear time threshold for CAG that predicted survival to discharge.
Cardiopulmonary Resuscitation
;
Coronary Angiography*
;
Coronary Artery Disease
;
Emergency Service, Hospital
;
Humans
;
Male
;
Myocardial Infarction
;
Out-of-Hospital Cardiac Arrest*
;
Prognosis
;
Survival Rate
;
Survivors
9.Carotid Artery End-Diastolic Velocity and Future Cerebro-Cardiovascular Events in Asymptomatic High Risk Patients.
Hyemoon CHUNG ; Young Hak JUNG ; Ki Hyun KIM ; Jong Youn KIM ; Pil Ki MIN ; Young Won YOON ; Byoung Kwon LEE ; Bum Kee HONG ; Se Joong RIM ; Hyuck Moon KWON ; Eui Young CHOI
Korean Circulation Journal 2016;46(1):72-78
BACKGROUND AND OBJECTIVES: Prognostic value of additional carotid Doppler evaluations to carotid intima-media thickness (IMT) and plaque has not been completely evaluated. SUBJECTS AND METHODS: A total of 1119 patients with risk factors for, but without, overt coronary artery disease (CAD), who underwent both carotid ultrasound and Doppler examination were included in the present study. Parameters of interest included peak systolic and end-diastolic velocities, resistive indices of the carotid arteries, IMT, and plaque measurements. The primary end-point was all-cause cerebro-cardiovascular events (CVEs) including acute myocardial infarction, coronary revascularization therapy, heart failure admission, stroke, and cardiovascular death. Model 1 covariates comprised age and sex; Model 2 also included hypertension, diabetes and smoking; Model 3 also had use of aspirin and statin; and Model 4 also included IMT and plaque. RESULTS: The mean follow-up duration was 1386+/-461 days and the mean age of the study population was 60+/-12 years. Amongst 1119 participants, 43% were women, 57% had a history of hypertension, and 23% had diabetes. During follow-up, 6.6% of patients experienced CVEs. Among carotid Doppler parameters, average common carotid artery end-diastolic velocity was the independent predictor for future CVEs after adjustments for all models variables (HR 0.95 per cm/s, 95% confident interval 0.91-0.99, p=0.034 in Model 4) and significantly increased the predictive value of Model 4 (global chi2=59.0 vs. 62.8, p=0.029). CONCLUSION: Carotid Doppler measurements in addition to IMT and plaque evaluation are independently associated with future CVEs in asymptomatic patients at risk for CAD.
Aspirin
;
Carotid Arteries
;
Carotid Artery, Common
;
Carotid Intima-Media Thickness
;
Coronary Artery Disease
;
Female
;
Follow-Up Studies
;
Heart Failure
;
Humans
;
Hydroxymethylglutaryl-CoA Reductase Inhibitors
;
Hypertension
;
Myocardial Infarction
;
Risk Factors
;
Smoke
;
Smoking
;
Stroke
;
Ultrasonography
10.Prognostic Value of Elevated Homocysteine Levels in Korean Patients with Coronary Artery Disease: A Propensity Score Matched Analysis.
Sung Woo KWON ; Jong Youn KIM ; Young Ju SUH ; Dae Hyung LEE ; Young Won YOON ; Byoung Kwon LEE ; Young Hak JUNG ; Eui Young CHOI ; Bum Kee HONG ; Se Joong RIM ; Hyuck Moon KWON
Korean Circulation Journal 2016;46(2):154-160
BACKGROUND AND OBJECTIVES: We sought to determine whether an elevated homocysteine (Hcy) level is associated with a worse prognosis in Korean patients with coronary artery disease (CAD). SUBJECTS AND METHODS: A total of 5839 patients (60.4% male, mean age 61.3±11.2 years) with CAD were enrolled from 2000 to 2010 at Gangnam Severance Hospital. CAD was diagnosed by invasive coronary angiography. Laboratory values including Hcy level were obtained on the day of coronary angiography and analyses were performed shortly after sampling. Patients were divided into two groups according to their Hcy levels. Baseline risk factors, coronary angiographic findings, length of follow-up, and composite endpoints including cardiac death (CD) and non-fatal myocardial infarction (NFMI) were recorded. 1:1 propensity score matched analysis was also performed. RESULTS: Over a mean follow-up period of 4.4±2.5 years, there were 132 composite endpoints (75 CD and 57 NFMI) with an event rate of 2.3%. Mean Hcy level was 9.9±4.3 µmol/L (normal Hcy 7.9±1.5 µmol/L and elevated Hcy 13.9±5.1 µmol/L). Kaplan-Meier survival analysis showed an association of elevated Hcy level with worse prognosis (p<0.0001). In addition, a multivariate Cox regression analysis showed an association of elevated Hcy level with worse prognosis for both the entire cohort (hazard ratio [HR] 2.077, 95% confidence interval [CI] 1.467-2.941, p<0.0001) and the propensity score matched cohort (HR 1.982, 95% CI 1.305-3.009, p=0.001). CONCLUSION: Elevated Hcy level is associated with worse outcomes in Korean patients with CAD.
Cohort Studies
;
Coronary Angiography
;
Coronary Artery Disease*
;
Coronary Vessels*
;
Death
;
Follow-Up Studies
;
Homocysteine*
;
Humans
;
Male
;
Myocardial Infarction
;
Prognosis
;
Propensity Score*
;
Risk Factors

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