Changes of Mortality and Morbidity of Very Low Birth Weight Infants after Neonatal Intensive Care Unit Strategy Alteration in a Single Center: Comparison with 2015 Korean Neonatal Network Report

PURPOSE: The purpose of this study was to investigate the outcome after changes in the treatment strategies for very low birth weight infant (VLBWI) in a single neonatal intensive care unit (NICU) center. METHODS: We performed a retrospective review of 300 VLBWI born from 1st January 2010 to 31th December 2016. We compared the outcomes including survival rate, birth weight (BW), gestational age (GA), and morbidities between period I (2010–2013, P-I) and period II (2014–2016, P-II). RESULTS: The average survival rate was not different between P-I and P-II. However, the survival rate of ≤24 weeks' GA, 25 weeks' GA, 26 weeks' GA were 57%, 69%, 93% respectively in P-II and 31%, 59%, 87% in P-I respectively. The survival rate of infants with birth weight <500 g, 500–749 g, 750–999 g were 100%, 55%, 90% respectively in P-II and 50%, 24%, 80%, respectively in P-I. The incidence of bronchopulmonary dysplasia (BPD) was higher in P-II than in P-I (P=0.012) and moderate-to-severe BPD was also higher in P-II (P=0.004). Incidence of patent ductus arteriosus (PDA) with treatment, necrotizing enterocolitis (stage≥2), and abnormal brain sonography were significantly lower in P-II (P=0.027, P=0.032, P=0.005). Incidences of retinopathy of prematurity (ROP) with laser treatment and early sepsis were not different. CONCLUSION: The survival rate and complications of VLBWI were improved in period II, especially in less than 750 g and below 26 weeks, except incidence of BPD. Changes of NICU strategies were effective to improve mortality and morbidity in VLBWI.

Performance evaluation of the HepB Typer-Entecavir kit for detection of entecavir resistance mutations in chronic hepatitis B

BACKGROUND/AIMS: Molecular diagnostic methods have enabled the rapid diagnosis of drug-resistant mutations in hepatitis B virus (HBV) and have reduced both unnecessary therapeutic interventions and medical costs. In this study we evaluated the analytical and clinical performances of the HepB Typer-Entecavir kit (GeneMatrix, Korea) in detecting entecavir-resistance-associated mutations. METHODS: The HepB Typer-Entecavir kit was evaluated for its limit of detection, interference, cross-reactivity, and precision using HBV reference standards made by diluting high-titer viral stocks in HBV-negative human serum. The performance of the HepB Typer-Entecavir kit for detecting mutations related to entecavir resistance was compared with direct sequencing for 396 clinical samples from 108 patients. RESULTS: Using the reference standards, the detection limit of the HepB Typer-Entecavir kit was found to be as low as 500 copies/mL. No cross-reactivity was observed, and elevated levels of various interfering substances did not adversely affect its analytical performance. The precision test conducted by repetitive analysis of 2,400 replicates with reference standards at various concentrations showed 99.9% agreement (2398/2400). The overall concordance rate between the HepB Typer-Entecavir kit and direct sequencing assays in 396 clinical samples was 99.5%. CONCLUSIONS: The HepB Typer-Entecavir kit showed high reliability and precision, and comparable sensitivity and specificity for detecting mutant virus populations in reference and clinical samples in comparison with direct sequencing. Therefore, this assay would be clinically useful in the diagnosis of entecavir-resistance-associated mutations in chronic hepatitis B.

Association Analysis of SERPINB5 Polymorphisms with HBV Clearance and HCC Occurrence in a Korean Population

Serpin peptidase inhibitor, Clade B (ovalbumin), Member 5 (SERPINB5), also known as maspin, is a potent tumor suppressor gene. It has correlations with many tumor cells, from pancreas cancer to breast cancer, so it is possible that it may also affect liver cancer. There has also been a report that SERPINB12, a gene placed right next to SERPINB5, is expressed in liver. For this study, 32 polymorphisms were identified in SERPINB5 by direct DNA sequencing, and 11 of them were selected to be tested with a larger scale subjects. The association of the 11 SERPINB5 polymorphisms with Hepatitis B virus (HBV) clearance, hepatocellular carcinoma (HCC) occurrence and the onset age of HCC were analyzed. There were no significant associations found between 11 SERPINB5 polymorphisms and HBV clearance. In the case of HCC occurrence, one of the haplotypes (ht) showed association with HCC occurrence (OR=2.26, p=0.005, P(Cor)=0.05), albeit with a low statistical power (40.8%) and haplotype frequency (0.052). Further study with a bigger sample size will be needed to clearly verify the association between ht5 and HCC occurrence.

Putative Association of ITGB1 Haplotype with the Clearance of HBV Infection

Integrins are transmembrane receptor proteins that mediate cell-cell adhesion and cell-extracellular matrix (ECM) adhesion. The deregulation of cell-ECM adhesion and the abnormal expression of beta1 (beta1) integrins (ITGB1s) are involved in tumor development and metastasis. In the liver, the expression of integrins and ECM proteins can be a cause of hepatocellular carcinoma (HCC) development. We performed direct DNA sequencing of 24 individuals, and identified 23 sequence variants of ITGB1 polymorphisms. Among these 23 variants, 7 common variants were selected based on frequencies and linkage disequilibrium, and then genotyped in a larger-scale group of subjects (n=1,103). The genetic associations of ITGB1 polymorphisms with the clearance of HBV and HCC outcome of HBV patients were analyzed using logistic regression models and Cox relative hazard models. Although there was no significant association observed between the polymorphisms and the HCC outcome of HBV patients, the second most common haplotype (ITGB1 haplotype-2 [C-C-C-C-T-C-T]) was putatively associated with HBV clearance (OR=0.75, p=0.008 and P(corr)=0.05). The minor allele frequency (MAF) of ITGB1 haplotype-2 of the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier group (CC) (freq. = 0.248 vs. 0.199). The information derived from this study could be valuable for understanding the genetic factors involved in the clearance of HBV.

Identification of Polymorphisms in CYP2E1 Gene and Association Analysis among Chronic HBV Patients

Cytochrome P450 2E1 (CYP2E1) is a member of the cytochrome P450 superfamily, and it is a key enzyme responsible for the metabolic activation of many smallmolecular-weight compounds such as alcohol, which is classified as a human carcinogen. In this study, we identified 19 single nucleotide polymorphisms (SNPs) in CYP2E1 in Korean population. In these SNPs, we examined possible genetic association of CYP2E1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Five common polymorphic sites were selected, CYP2E1 polymorphisms at rs381-3867, rs3813870, rs2070673, rs2515641 and rs2480257 , considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n=1,092). Statistical analysis demonstrated that CYP2E1 polymorphisms and haplotypes show no significant association with HBV clearance, HCC occurrence and onset age of HCC (p>0.05). Previous studies, however, have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk. Comparing the contrasting results of previous researches suggest that CYP2E1 polymorphism is associated with CYP2E1 activity induced by ethanol, but is not directly associated with HCC risk. CYP2E1 variation/haploype information identified in this study will provide valuable information for future studies on CYP2E1.

Lack of Association of BIRC5 Polymorphisms with Clearance of HBV Infection and HCC Occurrence in a Korean Population

BIRC5 (Survivin) belongs to the inhibitor of apoptosis gene family. The BIRC5 protein inhibits caspases and consequently blocks apoptosis. Thus, BIRC5 contributes to the progression of cancer allowing for continued cell proliferation and survival. In this study, we identified eight sequence variants of BIRC5 through direct DNA sequencing. Among the eight single nucleotide polymorphisms (SNPs), six common variants with frequencies higher than 0.05 were selected for larger-scale genotyping (n=1,066). Results of the study did not show any association between the promoter region polymorphisms and the clearance of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence. This is in line with a previous study in which polymorphisms in the promoter region does not influence the function of BIRC5. Initially, we were able to detect a signal with the +9194A>G, which disappeared after multiple corrections but led to a change in amino acid. Similarly, we were also able to detect an association signal between two haplotypes (haplotype-2 and haplotype- 5) on the onset age of HCC and/or HCC occurrence, but the signals also disappeared after multiple corrections. As a result, we concluded that there was no association between BIRC5 polymorphisms and the clearance HBV infection and/or HCC occurrence. However, our results might useful to future studies.

Evaluation of the Patterns of Fractures and the Soft Tissue Injury Using MRI in Tibial Plateau Fractures

PURPOSE: To compare information about fracture type in MRI with simple radiograph in tibial plateau fractures and evaluate tibial plateau fractures type and accompanying soft tissue injury, and evaluate usefulness of MRI in tibial plateau fractures. MATERIALS AND METHODS: Compared MRI with simple radiograph about Schatzker classification, depression of articular surface and displacement of bone fragment from the 68 examples who checked MRI and we evaluated soft tissue injury around knee joint. RESULTS: There were 7 examples of Schatzker type change after MRI check. Average depression of articular surface in simple radiograph was 2.93 mm and 4.28 mm in MRI. It increased by 1.35 mm and it was meaningful statistically (p<0.05). There was no significant difference between MRI and simple radiograph of displaced bone fragment (p=0.168). There were 58 (85.3%) cases of soft tissue injury in MRI. CONCLUSION: MRI can find additional fracture line or articular depression that can't be found in simple radiograph and gives more information about articular depression and soft tissue that is useful in surgical plans. I think preoperative MRI is necessary to better treatment of fracture & treatment of periarticular soft tissue injury in tibial plateau fracture.

Treatment of Diaphyseal Fractures of Forearm Both Bones: Comparison between Plate Fixation and Rush Pin Intramedullary Nailing

PURPOSE: To compare the functional results between the plate fixation and Rush pin insertion for the treatment of diaphyseal fractures of the forearm both bones. MATERIALS AND METHODS: We reviewed 51 patients who were treated for diaphyseal fractures of the both forearm bones from 1995 to 2003, and evaluated them with Anderson's method. Eighteen patients were treated with plate fixation of both bones (group I), 14 patients treated with of the Rush pin insertion of the radius and plate fixation of the ulna (group II), 11 patients treated with plate fixation of the radius and Rush pin insertion of the ulna (group III), and 8 patients treated with Rush pin insertion of forearm both bones (group IV). RESULTS: Seventeen out of eighteen cases obtained favorable result (94.4%) in group I, 12 out of 14 cases (85.7%) in group II, 7 out of 11 cases (63.3%) in group III, and 4 out of 8 cases (50.0%) in group IV with statistically significant differences between the groups (p=0.04). CONCLUSION: Plate fixation of forearm both bones yield the best result. Thus, plate fixation of both forearm bones is recommended in treating the diaphyseal fractures of both forearm bones. At least one bone is recommended to be fixed with a plate if it is not possible to fix both forearm bones with plates.

Treatment of Intercondylar Fractures of Humerus with Y-plate

PURPOSE: To evaluate the results of the treatment of intercondylar fractures of the humerus using Y-plate. MATERIALS AND METHODS: The subjects were 17 patients with intercondylar fracture of humerus who were treated using the Y-plate. Nine cases were C1 type, 4 were C2 type, and the remaining 4 were C3 type. 11 subjects had accompanying fractures of another part of the body. The average age was 48.8. The average follow up period was 33 months. We used Mayo Elbow Performance Score and Risborough-Radin's rating score for each patient as the methods of rating. RESULTS: The average range of motion of the elbow was 105 degrees (50~150 degrees). According to Cassebaum's classification for elbow range of motion, 7 cases were rated very good, 1 cases were good, 4 cases were fair, and 1 cases were poor. According to Mayo Elbow Performance Score, 7 were excellent, 7 were good, 2 fair, and 1 poor. Of the 3 patients who were fair or poor in Mayo Elbow Performance Score, 2 were type C3 fractures, and all 3 had major accompanying fractures. No significant postoperative complications developed in all cases. CONCLUSION: The fixation with Y-plate can still be a relatively good modality of treatment for interconylar fractures of the humerus in selected cases, in spite of the known mechanical weakness of the Y-plate. The patients with severe intra-articular comminution showed relatively poor results. And we think that the age of the patient and the energy of the injury have more or less influence on the results of treatment.

Subtalar Arthrodesis Using the Cannulated Compression Screw / 대한족부족관절학회지

PURPOSE: To analyze the overall clinical outcome, overall assessment, and patient's satisfaction rate of subtalar arthrodesis using the cannulated compression screw. MATERIALS AND METHODS: This study is based on 17 patients, 17 feet who underwent subtalar arthrodesis using the cannulated compression screw from March, 1997 to March, 2004 with at least 1 year follow-up. The average follow-up period was 33.0 months (12 to 72 months). Functional results were assessed using the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot (AOFAS) score, and Visual Analysis Scale (VAS) pain score, patients' returning to previous occupation and patients' satisfaction rate were also evaluated. RESULTS: The mean AOFAS scores at final follow-up were 80.4 points (range 66~92). The satisfactory rates were as follow. Thirteen patients (76.4%) were at least satisfied with surgical result at final follow-up. Patients' VAS pain score was average 2.8 points (1~6). Fourteen (82.3%) patients returned to previous job at mean postoperative period of 11.3 months (range 3-18 months). Patients' work efficiency after returning to previous occupation was 68.7% (range 33~100%). There were 9 complications which were 3 cases of sural nerve injury, 1 case of valgus malunion, and 5 cases of the hindfoot residual pain. CONCLUSION: We obtained the satisfactory functional results with relatively high patient satisfaction rate of 76%. So we conclude that subtalar arthrodesis using the cannulated compression screw is a reliable method for addressing the painful end-stage subtalar osteoarthritis and unreconstructible comminuted calcaneal fractures. However we also found out that average 11 months were necessary for patients to return to their job.

Subtalar Arthrodesis Using the Cannulated Compression Screw / 대한족부족관절학회지

PURPOSE: To analyze the overall clinical outcome, overall assessment, and patient's satisfaction rate of subtalar arthrodesis using the cannulated compression screw. MATERIALS AND METHODS: This study is based on 17 patients, 17 feet who underwent subtalar arthrodesis using the cannulated compression screw from March, 1997 to March, 2004 with at least 1 year follow-up. The average follow-up period was 33.0 months (12 to 72 months). Functional results were assessed using the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot (AOFAS) score, and Visual Analysis Scale (VAS) pain score, patients' returning to previous occupation and patients' satisfaction rate were also evaluated. RESULTS: The mean AOFAS scores at final follow-up were 80.4 points (range 66~92). The satisfactory rates were as follow. Thirteen patients (76.4%) were at least satisfied with surgical result at final follow-up. Patients' VAS pain score was average 2.8 points (1~6). Fourteen (82.3%) patients returned to previous job at mean postoperative period of 11.3 months (range 3-18 months). Patients' work efficiency after returning to previous occupation was 68.7% (range 33~100%). There were 9 complications which were 3 cases of sural nerve injury, 1 case of valgus malunion, and 5 cases of the hindfoot residual pain. CONCLUSION: We obtained the satisfactory functional results with relatively high patient satisfaction rate of 76%. So we conclude that subtalar arthrodesis using the cannulated compression screw is a reliable method for addressing the painful end-stage subtalar osteoarthritis and unreconstructible comminuted calcaneal fractures. However we also found out that average 11 months were necessary for patients to return to their job.

Treatment of Tibial Plateau Fractures using Ilizarov Fixation (Schatzker Type IV, V, VI)

PURPOSE: To evaluate the effectiveness of Ilizarov fixation in tibial plateua fractures (Schatzker type IV, V, VI), the clinical and radiological results were analysed retrospectively. MATERIALS AND METHODS: Of the tibial plateau fractures (Schatzker type IV, V, VI) which had been treated by using Ilizarov fixatrion method at Dankook university from June 1995 to June 2004, we clinically, radiologically analysed the 47 cases with follow-up study of a mean 38 months. Overall results which were evaluated according to Blokker's evaluation system. RESULTS: The average start time of the range of motion excercise was 4.2 weeks, and the average start time of partial weight bearing was 4.6 weeks. Results which were evaluated according to Blokker's evaluation systems were "satisfactory" in 8 cases (80%) of the type IV fractures, in 9 cases of the type V fracures, and in 18 cases (69%) of the type VI. Overall results were "satisfactory" in 35 cases (74.4%), "unsatisfactory" in 12 cases (25.5%). CONCLUSION: When use Ilizarov fixation in tibial plateau fracture (Schatzker type IV, V, VI), we have many advantages that the early start time of the range of motion, the early start time of weight bearing, the acceptable results of Blokker's evaluation system. Therefore, we conclude that Ilizarov fixation in tibial plateua fracure (Schatzker type IV, V, VI) is effective.