Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. @*Materials and Methods@#From January 2001 to December 2015, data of pediatric patients (0–18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. @*Results@#Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). @*Conclusion@#The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

Alterations of vital signs as prognostic factors after intraprocedural rupture of intracranial aneurysms during endovascular treatment

Objective@#To report our experience with intraprocedural rupture (IPR) of intracranial aneurysms during endovascular treatment and evaluate alterations in vital signs as independent prognostic factors to predict the outcomes of IPR. @*Methods@#Between January 2008 and August 2021, 34 patients (8 ruptured and 26 unruptured) were confirmed to have IPR based on our dataset with 3178 endovascular coiling procedures. The patients who underwent additional surgeries related to IPR were classified as the OP group (n=9), while those who did not receive additional surgeries were classified as the non-OP group (n=25). Vital signs were recorded during the procedure by anesthesiologists and analyzed. @*Results@#Of the 34 patients included in this study, eight initially presented with subarachnoid hemorrhage due to a ruptured aneurysm. The clinical outcomes at discharge were significantly different between the two groups (p=0.046). In the OP group, five patients showed favorable outcomes at discharge, while four showed unfavorable outcomes. In the non-OP group, 23 patients showed favorable outcomes at discharge while two patients showed unfavorable outcomes. Maximal (MAX) systolic blood pressure (SBP) (odds ratio [OR] 1.520, 95% confidence interval [CI] 1.084-2.110; p=0.037) and higher differential value MAX-median blood pressure (MBP) (OR 1.322, 95% CI 1.029-1.607; p=0.044) remained independent risk factors for poor prognosis after IPR on multivariate logistic regression analysis. @*Conclusions@#The MAX SBP and the difference between the maximal and baseline values of MBP are key factors in predicting the prognosis of patients after IPR, as well as providing useful information for predicting the outcome. Further research is required to confirm the relationship between naive pressure and prognosis.

Retreatment of a recurrent giant aneurysm of the internal carotid artery after treatment with a flow-diverting stent

Flow-diverting stents (FDSs) have proven advantageous for the treatment of large, fusiform, and dissecting aneurysms that are otherwise difficult to treat. Retreatment strategies for recurrent large or giant aneurysms after FDSs are limited to overlapping implantation of an additional FDS or definitive occlusion of the parent vessel. We report a recurrent giant aneurysm that was initially treated with an FDS with coils and was successfully treated with an additional FDS. Visual symptoms due to the mass effect of the recurrent aneurysm were completely resolved, and follow-up digital subtraction angiography revealed complete obliteration of the aneurysm. Additional FDS implantation for the retreatment of incompletely occluded aneurysms after the initial FDS treatment may be feasible and safe. Further studies are required to validate these results.

Uncharted Diversity and Ecology of Saprolegniaceae (Oomycota) in Freshwater Environments

The fungal-like family Saprolegniaceae (Oomycota), also called “water mold,” includes mostly aquatic saprophytes as well as notorious aquatic animal pathogens. Most studies on Saprolegniaceae have been biased toward pathogenic species that are important to aquaculture rather than saprotrophic species, despite the latter’s crucial roles in carbon cycling of freshwater ecosystems. Few attempts have been made to study the diversity and ecology of Saprolegniaceae; thus, their ecological role is not well-known. During a survey of oomycetes between 2016 and 2021, we investigated the diversity and distribution of culturable Saprolegniaceae species in freshwater ecosystems of Korea. In the present study, members of Saprolegniaceae were isolated and identified at species level based on their cultural, morphological, and molecular phylogenetic analyses. Furthermore, substrate preference and seasonal dynamics for each were examined. Most of the species were previously reported as animal pathogens; however, in the present study, they were often isolated from other freshwater substrates, such as plant debris, algae, water, and soil sediment. The relative abundance of Saprolegniaceae was higher in the cold to cool season than that in the warm to hot season of Korea. This study enhances our understanding of the diversity and ecological attributes of Saprolegniaceae in freshwater ecosystems.

Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea. @*Materials and Methods@#Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively. @*Results@#Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020). @*Conclusion@#This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

Role of Transarterial Embolization in the Treatment of Life-Threatening Hemorrhage in Patients With Maxillofacial Injury / 대한신경손상학회지

Life-threatening hemorrhage following maxillofacial injury (MFI) is rare but can be fatal. Conventional measures for hemostasis including nasal packing, balloon tamponade, and surgical ligation of bleeding points may not be effective or efficient in patients at risk of hypovolemic shock. Advantages of transarterial embolization (TAE) include rapid identification of the bleeding focus and its access, direct obstruction of the culprit vessels, ability to control multiple bleeding sites, and no requirement of general anesthesia. The internal maxillary artery is the most frequently targeted vessel for embolization. Several studies have demonstrated that TAE was technically successful at rates between 79.4% and 100% and was associated with good clinical outcomes. However, major complications such as tongue necrosis or facial nerve palsy have rarely been reported (0%–7%), probably because of rich collaterals in the maxillofacial region, and failure to diagnose complications in patients who are severely disabled or died. Traditionally, Gelfoam and coils have been widely used as embolic materials. Polyvinyl alcohol particles and n-butyl-cyanoacrylate are also favored, and newer embolic materials, such as Onyx or precipitating hydrophobic injectable liquid, are available for use. Operators should be familiar with the distinctive characteristics of each embolic material. Early treatment with TAE for intractable hemorrhage may improve outcomes in patients with MFI, and further studies are necessary to develop a treatment algorithm to define when to initiate TAE in cases of severe oronasal hemorrhage following MFI.

Complications of Cranioplasty Following Decompressive Craniectomy: Risk Factors of Complications and Comparison Between Autogenous and Artificial Bones / 대한신경손상학회지

Objectives@#Craniectomy is widely performed to lower the intracranial pressure in various conditions, such as traumatic brain injury, stroke, or brain swelling. Several complications can occur after craniectomy and cranioplasty, which significantly affect the prognosis of the patients after surgery. We studied the complications of craniectomy and cranioplasty and the factors affecting prognosis after the operation. @*Methods@#Patients who underwent cranioplasty after craniectomy at Daejeon St. Mary’s Hospital from 2015 to 2021 were included. We retrospectively reviewed their medical records and images. All patients were classified according to their sex, age, clinical grade, and diagnosis. Complications after craniectomy and cranioplasty were investigated for 1 year after surgery. The complications included postoperative hemorrhage, infection, hydrocephalus, and bone resorption. @*Results@#This study included 104 patients. Complications after decompressive craniectomy were significantly frequent in patients with hypertension history (p=0.03). In contrast, complications of cranioplasty were significantly frequent in patients with history of diabetes mellitus, hepatic failure, or trauma (p=0.03, p<0.01, and p=0.01, respectively). Artificial bones were used more frequently than autologous bones in patients with trauma (p=0.03); however, there was no difference in the incidence of complications between them (p=0.64). @*Conclusion@#Hypertension is a significant risk factor for decompressive craniectomy complications, especially rebleeding. Diabetes, hepatic failure, and trauma are significant risk factors for cranioplasty complications. There was no statistical difference in the incidence of complications between the use of autologous and artificial bones.

Delays in Intracerebral Hemorrhage Management Is Associated with Hematoma Expansion and Worse Outcomes: Changes in COVID-19 Era

Purpose@#The coronavirus disease 2019 (COVID-19) pandemic disrupted the emergency medical care system worldwide. We analyzed the changes in the management of intracerebral hemorrhage (ICH) and compared the pre-COVID-19 and COVID-19 eras. @*Materials and Methods@#From March to October of the COVID-19 era (2020), 83 consecutive patients with ICH were admitted to four comprehensive stroke centers. We retrospectively reviewed the data of patients and compared the treatment workflow metrics, treatment modalities, and clinical outcomes with the patients admitted during the same period of pre-COVID-19 era (2017–2019). @*Results@#Three hundred thirty-eight patients (83 in COVID-19 era and 255 in pre-COVID-19 era) were included in this study. Symptom onset/detection-to-door time [COVID-19; 56.0 min (34.0–106.0), pre-COVID-19; 40.0 min (27.0–98.0), p=0.016] and median door to-intensive treatment time differed between the two groups [COVID-19; 349.0 min (177.0–560.0), pre-COVID-19; 184.0 min (134.0–271.0), p<0.001]. Hematoma expansion was detected more significantly in the COVID-19 era (39.8% vs. 22.1%, p=0.002). At 3-month follow-up, clinical outcomes of patients were worse in the COVID-19 era (Good modified Rankin Scale; 33.7% in COVID-19, 46.7% in pre-COVID-19, p=0.039). @*Conclusion@#During the COVID-19 era, delays in management of ICH was associated with hematoma expansion and worse outcomes.

Delays in Intracerebral Hemorrhage Management Is Associated with Hematoma Expansion and Worse Outcomes: Changes in COVID-19 Era

Purpose@#The coronavirus disease 2019 (COVID-19) pandemic disrupted the emergency medical care system worldwide. We analyzed the changes in the management of intracerebral hemorrhage (ICH) and compared the pre-COVID-19 and COVID-19 eras. @*Materials and Methods@#From March to October of the COVID-19 era (2020), 83 consecutive patients with ICH were admitted to four comprehensive stroke centers. We retrospectively reviewed the data of patients and compared the treatment workflow metrics, treatment modalities, and clinical outcomes with the patients admitted during the same period of pre-COVID-19 era (2017–2019). @*Results@#Three hundred thirty-eight patients (83 in COVID-19 era and 255 in pre-COVID-19 era) were included in this study. Symptom onset/detection-to-door time [COVID-19; 56.0 min (34.0–106.0), pre-COVID-19; 40.0 min (27.0–98.0), p=0.016] and median door to-intensive treatment time differed between the two groups [COVID-19; 349.0 min (177.0–560.0), pre-COVID-19; 184.0 min (134.0–271.0), p<0.001]. Hematoma expansion was detected more significantly in the COVID-19 era (39.8% vs. 22.1%, p=0.002). At 3-month follow-up, clinical outcomes of patients were worse in the COVID-19 era (Good modified Rankin Scale; 33.7% in COVID-19, 46.7% in pre-COVID-19, p=0.039). @*Conclusion@#During the COVID-19 era, delays in management of ICH was associated with hematoma expansion and worse outcomes.

Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma:a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study

Background@#Hodgkin's lymphoma (HL) constitutes 10%–20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea. @*Methods@#We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016. @*Results@#A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype.Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, highrisk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level.In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively. @*Conclusion@#This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.

Epidemiological Study of Hereditary Hemolytic Anemia in the Korean Pediatric Population during 1997–2016: a Nationwide Retrospective Cohort Study

Background@#Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. @*Methods@#We collected the data of a newly diagnosed pediatric HHA cohort (2007–2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997–2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. @*Results@#A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. @*Conclusion@#In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.

Risk Factor Analysis for Secondary Malignancy in Dexrazoxane-Treated Pediatric Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Dexrazoxane has been used as an effective cardioprotector against anthracycline cardiotoxicity. This study intended to analyze cardioprotective efficacy and secondary malignancy development, and elucidate risk factors for secondary malignancies in dexrazoxane-treated pediatric patients. MATERIALS AND METHODS: Data was collected from 15 hospitals in Korea. Patients who received any anthracyclines, and completed treatment without stem cell transplantation were included. For efficacy evaluation, the incidence of cardiac events and cardiac event-free survival rates were compared. Data about risk factors of secondary malignancies were collected. RESULTS: Data of total 1,453 cases were analyzed; dexrazoxane with every anthracyclines group (D group, 1,035 patients) and no dexrazoxane group (non-D group, 418 patients). Incidence of the reported cardiac events was not statistically different between two groups; however, the cardiac event-free survival rate of patients with more than 400 mg/m2 of anthracyclines was significantly higher in D group (91.2% vs. 80.1%, p=0.04). The 6-year cumulative incidence of secondary malignancy was not different between both groups after considering follow-up duration difference (non-D, 0.52%±0.37%; D, 0.60%±0.28%; p=0.55). The most influential risk factor for secondary malignancy was the duration of anthracycline administration according to multivariate analysis. CONCLUSION: Dexrazoxane had an efficacy in lowering cardiac event-free survival rates in patients with higher cumulative anthracyclines. As a result of multivariate analysis for assessing risk factors of secondary malignancy, the occurrence of secondary malignancy was not related to dexrazoxane administration.

Clinical Significance of Extraluminal Compressions according to the Site of the Duodenum

BACKGROUND/AIMS: Differentiating extraluminal compressions from true subepithelial tumors in the duodenum by endoscopy alone is difficult. Endoscopic ultrasonography (EUS) is one of the most useful diagnostic modalities for this purpose. Extraluminal compression in the duodenum is occasionally observed, but its clinical significance has not been reported. Therefore, the aim of this study was to evaluate the clinical significance of extraluminal compression in the duodenum according to lesion location. MATERIALS AND METHODS: We retrospectively evaluated 22 patients diagnosed as having extraluminal compression in the duodenum based on EUS findings between January 2006 and December 2017. Some patients underwent abdominal computed tomography for accurate diagnosis. RESULTS: The location of the extraluminal compression was the duodenal bulb in 10 cases, the superior duodenal angle in 10 cases, and the second portion of the duodenum in 2 cases. Of the 22 cases, 12 were caused by normal structures, including vessels, the right kidney, the gallbladder, and the pancreas, and 10 were caused by pathological lesions, including the hepatic cyst, remnant cystic duct and dilated common bile duct after cholecystectomy; gallstones, gallbladder polyps, remnant cystic duct cancer, and pseudomyxoma peritoneii. The anterior wall of the duodenum was the most frequent location of extraluminal compression. However, the lesions in the anterior wall of the duodenal bulb and superior duodenal angle showed a high frequency of pathologic lesions, including malignancy. CONCLUSIONS: If the extraluminal compression is found in the anterior wall of the duodenum, EUS is needed because of the high frequency of pathological lesions.

A Multicenter Study on von Willebrand Disease Realities in Yeungnam Region / 임상소아혈액종양

BACKGROUND: von Willebrand disease (VWD) is one of the most common inherited bleeding disorders. However, the number of patients who register to the Korea Hemophilia Foundation (KHF) is much lower than the expected prevalence rate and only few hospitals perform tests for diagnosis autonomously. Thus, we surveyed practical realities of VWD in Yeungnam region. METHODS: Patients with VWD (N=267) who were diagnosed at eleven university hospitals from March 1995 to March 2018 were enrolled in this study. We evaluated the medical records from each hospital retrospectively. RESULTS: Two hundred and twenty-eight children and 39 adults met the diagnostic criteria for VWD. Seventy-eight (57.4%) patients had the blood type O. Fifty-eight patients were definite type 1 (21.7%), 151 were possible type 1 (56.6%), and the others were type 2. Abnormal laboratory findings were the most common factor for the diagnosis in children. VWF mutations were detected in 17 patients. Patients with a family history showed age of diagnosis of 9 y, which is higher than in those with no family history (6 yr), and also showed a higher rate of significant bleeding (32.1% vs. 14.2%). VWF:RCo and VWF:Ag tests were performed in-hospital at only 1 of 11 hospitals. Twelve of 267 patients were enrolled at the KHF (4.5%). CONCLUSION: A high rate of out-sourcing studies may result in inaccurate diagnosis. The registration rate to the KHF is still lower than the prevalence rate. A comprehensive nationwide registration system is necessary in order to identify the actual prevalence rate and promote the diagnosis of VWD in Korea.

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

BACKGROUND: The 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). METHODS: A 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. RESULTS: All 10 enrolled Korean patients receiving rurioctocog alfa pegol (9 prophylaxis, 1 on-demand) 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 prophylaxis regimen. No serious AEs were reported; all 9 nonserious AEs (in 3 patients) were mild in severity and unrelated to the study treatment. CONCLUSION: This 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.

Molecular Genetics of von Willebrand Disease in Korean Patients: Novel Variants and Limited Diagnostic Utility of Multiplex Ligation-Dependent Probe Amplification Analyses

BACKGROUND: von Willebrand disease (VWD), characterized by quantitative or qualitative defects of von Willebrand factor (VWF), is the most common inheritable bleeding disorder. Data regarding the genetic background of VWD in Korean patients is limited. To our knowledge, this is the first comprehensive molecular genetic investigation of Korean patients with VWD. METHODS: Twenty-two unrelated patients with VWD were recruited from August 2014 to December 2017 (age range 28 months–64 years; male:female ratio 1.2:1). Fifteen patients had type 1, six had type 2, and one had type 3 VWD. Blood samples were collected for coagulation analyses and molecular genetic analyses from each patient. Direct sequencing of all exons, flanking intronic sequences, and the promoter of VWF was performed. In patients without sequence variants, multiplex ligation-dependent probe amplification (MLPA) was performed to detect dosage variants. We adapted the American College of Medical Genetics and Genomics guidelines for variant interpretation and considered variants of uncertain significance, likely pathogenic variants, and pathogenic variants as putative disease-causing variants. RESULTS: VWF variants were identified in 15 patients (68%): 14 patients with a single heterozygous variant and one patient with two heterozygous variants. The variants consisted of 13 missense variants, one small insertion, and one splicing variant. Four variants were novel: p.S764Efs*16, p.C889R, p.C1130Y, and p.W2193C. MLPA analysis in seven patients without reportable variants revealed no dosage variants. CONCLUSIONS: This study revealed the spectrum of VWF variants, including novel ones, and limited diagnostic utility of MLPA analyses in Korean patients with VWD.

A Case of Anticoagulant-induced Spontaneous Intramural Intestinal Hematoma

Spontaneous intramural hematoma is a rare complication of oral anticoagulants, and its incidence is expected to increase because of the increasing number of elderly patients undergoing anticoagulant therapy. Clinical manifestations of spontaneous intramural hematoma vary from mild abdominal pain to intestinal obstruction or acute abdomen. Early diagnosis is important because most patients can be treated successfully without surgery. The role of endoscopy in the diagnosis of intramural hematoma is not well established because almost all cases are diagnosed non-invasively with computed tomography scans. However, confirmation of the intramural hematoma through direct visualization of the involved bowel mucosa is helpful, if the imaging diagnosis is uncertain. We report a case of anticoagulant-induced spontaneous intramural hematoma, which was diagnosed using endoscopy, with relevant literature review.

Safety and Efficacy of B-domain Deleted Third Generation Recombinant Factor VIII (GreenGene F™) in Korean Patients with Hemophilia A: Data from a Post-marketing Surveillance Study

BACKGROUND: New B-domain deleted third generation recombinant factor VIII (FVIII; GreenGene F™, beroctocog alfa) was launched in 2010. We determined safety and efficacy of GreenGene F™ during routine clinical practice in patients with hemophilia A over a period of 12 months. METHODS: From July 2010 to July 2014, a total of 136 hemophilia A patients were enrolled in a post-marketing surveillance (PMS) study. Among them, 134 patients were assessed for drug safety and 114 patients were analyzed for drug efficacy. Patients with differing hemophilia A severities and medical histories were monitored during 12 months of prophylactic and/or on-demand therapy. RESULTS: Among 134 patients evaluated, 85 (63.4%) had severe hemophilia. Ninety-two received a total of 1,266,077 units for prophylaxis, and 42 received 516,491 units for bleeding episodes. Three patients developed inhibitors. In 112 previously treated patients, one patient (0.9%) developed inhibitor after intensive FVIII treatment for surgery. Among 22 previously untreated patients, inhibitors were observed in 2 infants (9.1%). Overall, there were a total of 47 adverse events (other than inhibitors) of all types in 30 patients (22.4%), 11 in 10 patients (7.5%) of which were considered showing serious adverse events (SAEs); most of which were hemorrhages at different sites. None of the SAEs were judged as product related. An excellent/good efficacy rate of 91.3% for hemostasis and 89.4% for hemorrhage prevention was recorded. CONCLUSION: The results of this PMS study support the use of GreenGene F™ as safe and efficacious in hemorrhage prevention and treatment of hemophilia A. These results are consistent with the findings from previously published GreenGene F™ studies.

Bronchiolitis severity according to the infected viruses

PURPOSE: The aim of this study was to evaluate the severity of disease in children with acute bronchiolitis according to the type of infected virus. METHODS: From November 2007 to May 2015, 768 patients under 2 years of age who underwent real time-polymerase chain reaction of nasopharyngeal aspirates admitted to the Department of Pediatrics of Dongguk University Ilsan Hospital for acute bronchiolitis were enrolled. Severe bronchiolitis was defined as presence of one or more kinds among tachypnea, chest retraction, needs of O2 inhalation or ventilator care. RESULTS: The severity of bronchiolitis was increased with shorter fever duration (P < 0.001) and previous wheezing episodes (P = 0.005). In the case of single infection, respiratory syncytial virus (RSV) A only increased the severity of acute bronchiolitis (P = 0.012). However, the severity of illness decreased when RSV A coinfected with adenovirus (P = 0.034), human rhinovirus (P = 0.038), or human coronavirus NL63 (P = 0.042). On the other hand, when human rhinovirus was coinfected with enterovirus (P = 0.013) or parainfluenza 3 (P = 0.019), the severity was increased. When human metapneumovirus coinfected with human bocavirus, the severity was increased (P = 0.038). CONCLUSION: Acute bronchiolitis was associated with increased severity only when RSV A infected solely, but several viruses increased or decreased the severity when coinfection occurred. Therefore, it may be helpful in predicting the course of the acute bronchiolitis according to the affected virus.

Educational Interventions to Enhance Adherence to Prophylactic Treatment in Korean Hemophilia Patients / 임상소아혈액종양

BACKGROUND: A patient's adherence to prophylactic treatment is one of the most significant factors to achieve desired outcomes, in regards to the quality of life and treatment cost-effectiveness. The aim of this study is to evaluate the effectiveness of educational interventions in enhancing adherence to prophylactic treatment in Korean hemophilia patients. METHODS: The Validated Hemophilia Regimen Treatment Adherence Scale-Prophylaxis (VERITAS-Pro) was used to measure adherence. The study design consisted of two groups. One group was not educated with the education card which presented the morning administration of clotting factor concentrates and self-infusion skill. The other group was educated with the card. The scores of each subscale in the two groups and scores focused on the ‘Timing’ subscale were compared. RESULTS: Participants were recruited from five hemophilia treatment centers in Korea with 95 eligible patients forming the uneducated group and 123 patients in the educated group. The mean total score was 40.4 and 39.9, respectively. The subscale mean scores of the uneducated group and educated group were 8.43 and 7.90 (Timing), 6.12 and 5.88 (Dosing), 6.43 and 6.33 (Planning), 5.99 and 6.35 (Remembering), 6.22 and 6.25 (Skipping), and 7.23 and 7.24 (Communicating), respectively. CONCLUSION: Results showed that education programs on prophylactic treatment for hemophilia patients need to be well-designed with precise and subject-appropriate contents. Although the mean total scores of VERITAS-Pro could not be improved, the appropriate timing of injection with the educational intervention was administered. Results suggest that this whole process can enhance Korean hemophilia patients' adherence to prophylactic treatment.