Efficacy and safety of sofosbuvir-based regimens for treatment in chronic hepatitis C genotype 1 patients with moderately impaired renal function

BACKGROUND/AIMS: Treatment of chronic hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) is essential. The availability of sofosbuvir (SOF) has dramatically improved overall HCV cure rates, however there is insufficient data regarding its use in patients with CKD. We evaluated SOF in patients with hepatitis C genotype 1 (G1) and moderately impaired renal function. METHODS: We retrospectively reviewed all patients treated with a SOF-based regimen from December 2013 through September 2015 at Virginia Mason Medical Center. Data was then collected for HCV G1 patients with stage 3 CKD. RESULTS: A total of 28 patients with HCV G1 and stage 3 CKD were treated with a SOF-based regimen. Twenty-one patients had stage 3A CKD (estimated glomerular filtration rate [eGFR] 45–60 mL/min/1.73m2) and 7 patients had stage 3B CKD (eGFR 30–45 mL/min/1.73m2). The overall rate of sustained virologic response (SVR) 12 weeks after completion of therapy (SVR12) was 85.7% (24/28). SVR12 in stage 3A CKD patients was 81.0% (17/21) and in stage 3B CKD patients, SVR12 was 100% (7/7). Based on the treatment regimen used, the SVR12 was 81.8% (9/11), 92.3% (12/13), and 75.0% (3/4) for SOF/ledipasvir (LDV), SOF/simeprevir (SIM), and SOF/pegylated interferon (PEG)/ribavirin (RBV), respectively. Greater than 30% reduction eGFR was observed in 4 out of 28 patients. CONCLUSIONS: SOF-based regimens resulted in high SVR12 rates in patients with moderately impaired renal function. During therapy, HCV patients with CKD should be carefully monitored for worsening renal function.

Clinical features and short-term outcomes of pediatric acute fulminant myocarditis in a single center / 소아과

PURPOSE: The aims of this study were to document our single-center experience with pediatric acute fulminant myocarditis (AFM) and to investigate its clinical features and short-term outcomes. METHODS: We performed a retrospective chart review of all children 24 hours after admission in 4 of the 13 patients (30.7%), and 3 of those 4 patients (75%) died. CONCLUSION: AFM outcomes may be associated with complete atrioventricular block upon hospital admission, left ventricular fractional shortening at admission, time from admission to the initiation of ECMO support, initial brain natriuretic peptide level, and peak blood urea nitrogen level.

Outcome of Staged Repair of Tetralogy of Fallot with Pulmonary Atresia and a Ductus-dependent Pulmonary Circulation: Should Primary Repair Be Considered?

BACKGROUND: The tetralogy of Fallot (TOF) with pulmonary atresia (PA) and a ductus-dependent pulmonary circulation (no major aorto-pulmonary collateral arteries (MAPCAs)) has been treated with staged repair or primary repair depending on the preference of surgeons or institutions. We evaluated the 19-year outcome of staged repair for this anomaly to find out whether our surgical strategy should be changed. MATERIALS AND METHODS: Forty-four patients with TOF/PA with patent ductus arteriosus (PDA) who underwent staged repair from June 1991 to October 2010 were included in this retrospective study. The patients with MAPCAs were excluded. The average age at the first palliative shunt surgery was 40.8+/-67.5 days (range: 0~332 days). Thirty-one patients (31/44, 70%) were neonates. The average weight was 3.5+/-1.6 kg (range: 1.6~8.7 kg). A modified Blalock-Taussig (BT) shunt was performed in 38 patients, classic BT shunt in 4 patients, and central shunt in 2 patients. Six patients required concomitant procedures: pulmonary artery angioplasty was performed in 4 patients, pulmonary artery reconstruction in one patient, and re-implantation of the left pulmonary artery to the main pulmonary artery in one patient. Four patients required a second shunt operation before the definitive repair was performed. Thirty-three patients underwent definitive repair at 24.2+/-13.3 months (range: 7.3~68 months) after the first palliative operation. The average age at the time of definitive repair was 25.4+/-13.5 months (range: 7.6~68.6 months) and their average weight was 11.0+/-2.1 kg. For definitive repair, 3 types of right ventricular outflow procedures were used: extra-cardiac conduit was performed in 30 patients, trans-annular patch in 2 patients, and REV operation in 1 patient. One patient was lost to follow-up after hospital discharge. The mean follow-up duration for the rest of the patients was 72+/-37 months (range: 4~160 months). RESULTS: Ten patients (10/44, 22.7%) died before the definitive repair was performed. Four of them died during hospitalization after the shunt operation. Six deaths were thought to be shunt-related. The average time of shunt-related deaths after shunt procedures was 8.7 months (range: 2 days~25.3 months). There was no operative mortality after the definitive repair, but one patient died from dilated cardiomyopathy caused by myocarditis 8 years and 3 months after the definitive repair. Five-year and 10-year survival rates after the first palliative operation were 76.8% and 69.1%, respectively. CONCLUSION: There was a high overall mortality rate in staged repair for the patients with TOF/PA with PDA. Majority of deaths occurred before the definitive repair was performed. Therefore, primary repair or early second stage definitive repair should be considered to enhance the survival rate for patients with TOF/PA with PDA.

Quantitative Assessment Technology of Small Animal Myocardial Infarction PET Image Using Gaussian Mixture Model / 의학물리

Nuclear medicine images (SPECT, PET) were widely used tool for assessment of myocardial viability and perfusion. However it had difficult to define accurate myocardial infarct region. The purpose of this study was to investigate methodological approach for automatic measurement of rat myocardial infarct size using polar map with adaptive threshold. Rat myocardial infarction model was induced by ligation of the left circumflex artery. PET images were obtained after intravenous injection of 37 MBq 18F-FDG. After 60 min uptake, each animal was scanned for 20 min with ECG gating. PET data were reconstructed using ordered subset expectation maximization (OSEM) 2D. To automatically make the myocardial contour and generate polar map, we used QGS software (Cedars-Sinai Medical Center). The reference infarct size was defined by infarction area percentage of the total left myocardium using TTC staining. We used three threshold methods (predefined threshold, Otsu and Multi Gaussian mixture model; MGMM). Predefined threshold method was commonly used in other studies. We applied threshold value form 10% to 90% in step of 10%. Otsu algorithm calculated threshold with the maximum between class variance. MGMM method estimated the distribution of image intensity using multiple Gaussian mixture models (MGMM2, em leader MGMM5) and calculated adaptive threshold. The infarct size in polar map was calculated as the percentage of lower threshold area in polar map from the total polar map area. The measured infarct size using different threshold methods was evaluated by comparison with reference infarct size. The mean difference between with polar map defect size by predefined thresholds (20%, 30%, and 40%) and reference infarct size were 7.04+/-3.44%, 3.87+/-2.09% and 2.15+/-2.07%, respectively. Otsu verse reference infarct size was 3.56+/-4.16%. MGMM methods verse reference infarct size was 2.29+/-1.94%. The predefined threshold (30%) showed the smallest mean difference with reference infarct size. However, MGMM was more accurate than predefined threshold in under 10% reference infarct size case (MGMM: 0.006%, predefined threshold: 0.59%). In this study, we was to evaluate myocardial infarct size in polar map using multiple Gaussian mixture model. MGMM method was provide adaptive threshold in each subject and will be a useful for automatic measurement of infarct size.

Outcome of the Modified Norwood Procedure: 7 Years of Experience from a Single Institution / 대한흉부외과학회지

BACKGROUND: We assessed the early and mid-term results of the modified Norwood procedure for first-stage palliation of hypoplastic left heart syndrome (HLHS) and its variants to identify the risk factors for hospital mortality. MATERIAL AND METHOD: Between March, 2003, and December, 2009, 23 patients (18 males and 5 females) with HLHS or variants underwent the modified Norwood procedure. The age at operation ranged from 3 to 60 days (mean, 11.7+/-13.2 days) and weight at operation ranged from 2.2 to 4.8 kg (mean, 3.17+/-0.52 kg). We used a modified technique that spared the anterior wall of the main pulmonary artery in 20 patients. The sources of pulmonary blood flow were RV-PA conduit in 15 patients (group I) and RMBTS in 8 (group II). Follow-up was completed in 19 patients (19/20, 95%) in our hospital (mean 26.0+/-22.8 months). RESULT: Early death occurred in 3 patients (3/23, 13%), of whom 2 had TAPVC. Fourteen patients underwent subsequent bidirectional cavopulmonary connection (BCPC, stage 2) and seven underwent the Fontan operation (stage 3). Three patients died between stages, 2 before stage 2 and one before stage 3. The estimated 1-year and 5-year survival rates were 78% and 69%, respectively. On multivariate regression analysis, aberrant right subclavian artery (RSCA) and associated total anomalous pulmonary venous connection (TAPVC) were risk factors for hospital mortality after stage 1 Norwood procedure. CONCLUSION: HLHS and its variants can be palliated by the modified Norwood procedure with low operative mortality. Total anomalous pulmonary venous connection adversely affects the survival after a stage 1 Norwood procedure, and interstage mortality rates need to be improved.

Performance Measurement of Siemens Inveon PET Scanner for Small Animal Imaging / 의학물리

Inveon PET is a recently developed preclinical PET system for small animal. This study was conducted to measure the performance of Inveon PET as recommended by the NEMA NU 4-2008. We measured the spatial resolution, the sensitivity, the scatter fraction and the NECR using a F-18 source. A 3.432 ns coincidence window was used. A 1 mm3 sized F-18 point source was used for the measurement of spatial resolution within an energy window of 350~625 keV. PET acquisition was performed to obtain the spatial resolution from the center to the 5 cm offset toward the edge of the transverse FOV. Sensitivity, scatter fraction, and NECR were measured within an energy window of 350~750 keV. For measuring the sensitivity, a F-18 line source (length: 12.7 cm) was used with concentric 5 aluminum tubes. For the acquisition of the scatter fraction and the NECR, two NEMA scatter phantoms (rat: 50 mm in diameter, 150 mm in length; mouse: 25 mm in diameter, 70 mm in length) were used and the data for 14 half-lives (25.6 hr) was obtained using the F-18 line source (rat: 316 MBq, mouse: 206 MBq). The spatial resolution of the F-18 point source was 1.53, 1.50 and 2.33 mm in the radial, tangential and axial directions, respectively. The volumetric resolution was 5.43 mm3 in the center. The absolute sensitivity was 6.61%. The peak NECR was 486 kcps @121 MBq (rat phantom), and 1056 kcps @128 MBq (mouse phantom). The values of the scatter fraction were 20.59% and 7.93% in the rat and mouse phantoms, respectively. The performances of the Inveon animal PET scanner were measured in this study. This scanner will be useful for animal imaging.

Outcomes of the arterial switch operation in complete transposition of the great arteries / 소아과

PURPOSE: The arterial switch operation (ASO) has become the preferred procedure for the surgical management of transposition of the great arteries (TGA). We conducted a retrospective evaluation of our experience in 30 patients seen from January 2003 to July 2008, in order to determine outcomes and related risk factors after the arterial switch operation. METHODS: Patients charts, surgical reports, and echocardiograms were retrospectively reviewed. And they were analyzed in 2 different groups: complex (n=16) versus simple TGAs (n=14). Complex TGAs are TGAs with VSD or the Taussig-Bing anomaly with or without aortic arch anomalies. Simple TGAs are defined as TGAs with intact ventricular septum having no such anomalies. Median follow-up time was 44 months (3-63 months). RESULTS: Hospital mortality was 0%. However, follow-up echocardiographies revealed potential complications, including stenosis of the branch pulmonary arteries, neo-aortic and/or neo-pulmonary valvar regurgitation, and right or left ventricular outflow tract obstructions. Great arterial relationship (side-by-side), association of aortic arch anomalies, and the existence of the Taussig-Bing anomaly were assessed as significant risk factors of neo-aortic and/or neo-pulmonary valvar regurgitation in this series. On the other hand, right or left ventricular outflow tract obstructions were more frequently found in patients demonstrating VSD, side-by-side positioned great arteries, or associated coronary anomalies. CONCLUSION: The ASO is the procedure of choice in the treatment of TGA. However, special attention and follow-ups are needed to detect residual problems like the stenosis of the branch pulmonary arteries, neo-aortic and/or neo-pulmonary valvar regurgitation, as well as ventricular outflow tract obstructions.

Change of neutrophil count after treatment of intravenous immunoglobulin in children with idiopathic thrombocytopenic purpura / 소아과

PURPOSE: The aim of this study was to investigate the incidence and course of neutropenia following intravenous immunoglobulin (IVIG) therapy in children with idiopathic thrombocytopenic purpura (ITP). METHODS: From January 2001 to June 2006, fifty-four patients with ITP were enrolled in this study. Forty-two of 54 patients were treated with IVIG, while the other 12 were treated with anti-D immunoglobulin (Anti-D Ig). Post-treatment absolute neutrophil counts (ANC) were compared between patients who received IVIG and those who received Anti-D Ig. Comparison of post-treatment ANC between patients who treated with two different IVIG regimens (400 mg/kg/day for 5 days and 1 g/kg/day for 2 days) was also performed. RESULTS: Pretreatment ANC were not significantly different between the two treatment groups. After treatment with IVIG, 32 out of 42 patients (76.2%) showed more than 50% decrease of ANC from the baseline. On the other hand, only 2 out of 12 patients (16.7%) showed more than 50% decrease of ANC from the baseline after treatment Anti-D Ig. No significant difference was observed in the decline of ANC between the first IVIG treatment (42 patients) and repeated IVIG treatment groups (7 patients). There was no statistical difference in post-treatment ANC between patients who treated with two different IVIG regimens. The neutropenia induced by IVIG had resolved spontaneously in 38 out of 39 patients (97%) after several days. CONCLUSION: Neutropenia following IVIG administration may not be an uncommon finding in children with ITP. It seems to be transient and self limited.

The Clinical Features of Chronic Neonatal Hepatitis: Non-familial, Non-metabolic and Non-A, B, C Viral Hepatitis / 대한소아소화기영양학회지

PURPOSE: Neonatal hepatitis is the major cause of neonatal cholestasis and may be divided into infectious, metabolic, genetic, and idiopathic neonatal hepatitis. Non-familial, non-metabolic, and non-A, B, C viral neonatal hepatitis is known to have made satisfactory progress, but little is known about its chronic clinical features. METHODS: Clinical and histological assessments were carried out in 34 cases with chronic neonatal hepatitis [elevated serum alanine aminotrasferase (ALT) level for more than 6 months] except for A, B, C viral hepatitis, metabolic, or genetic neonatal hepatitis, who were admitted to the Department of Pediatrics, Pusan National University Hospital, from January 1998 to January 2004. RESULTS: Males were more common (70%). Jaundice (100%) and hepatomegaly (44%) were frequent manifestations. Peak serum ALT levels were most commonly below 300 IU/L in 41.2% of patients and peak serum direct bilirubin levels were most commonly between 1.0~5.0 mg/dL in 50% of patients. Ten cases (34%) of 29 patients had positive serum cytomegalovirus (CMV) IgM or urine CMV polymerase chain reaction. Serum ALT level was normalized within 1 year in 11 (37.9%) of 29 cases, and within 2 years in 9 (69.2%) of 13 cases. Serum ALT level was elevated persistently over 2 years in four (30.7%) of 13 cases. Histologic findings such as portal or periportal activity, lobular necrosis, portal or periportal fibrosis were more severe in patients with persistent ALT elevation over 2 years than in those showing normalization of ALT within 2 years (p>0.05). CONCLUSION: When the elevation of ALT level sustains over 1 year in non-familiar, non-metabolic, non-A, B, C viral neonatal hepatitis, an assessment of the severity of liver injury and a careful monitoring about chronic liver disease may be required.

A Case of Pulmonary Sequestration with Pleural Effusion / 소아과

Congenital pleural effusions are uncommon. The majority of cases are due to chylothorax, hydrops fetalis, and infection. Effusions of this nature are, for the most part, self-limited. We experienced a rare case of a congenital unilateral pleural effusion due to an extralobar sequestraion with pulmonary lymphangiectasia. Pleural effusion was found by antenatal ultrasonography and confirmed by CT scans and CT angiography of the chest in the neonatal period. The patient underwent an open thoracotomy where extralobar sequestraion located between the diaphragm and the left lower lobe was removed. His postoperative course was uncomplicated and there was complete resolution of the pleural effusion.

A Comparison with Infusion of Single Intravenous Anesthetic with Propofol and Fentanyl in Operation of Short Duration / 대한마취과학회지

BACKGROUND: Propofol, a new intravenous anesthetic agent, is now used for brief operation and day surgery for its rapid recovery and controllability. Propofol, rapid acting sedatives hypnotics, is known to no analgesic effect. This study was taken to evaluate the analgesic effect of propofol, compared to those of fentanyl. METHODS: Forty patients (ASA physical status 1, 2) scheduled for surgery of short duration (within 1 hour) were randomly allocated into two groups. Induction of anesthesia was performed by injection of thiopental (5 mg/kg) and succinylcholine (1 mg/kg) and ventilated with O2-N2O (50%) after endotracheal intubation. Maintenance of anesthesia was performed by vecuronium (1 mg/kg) and continuous infusion of propofol (group I) or fentanyl (group II). RESULTS: There was no significant differences in systolic and diastolic blood pressure in both groups. In heart rate, there was significant difference at preincision and postincision between two groups. Time to extubation (4.5 +/- 4.6 vs 6.3 +/- 4.6 min), time to eye open (7.5 +/- 7.1 vs 6.6 +/- 5.4 min), time to complain pain after stop dropping at recovery room (30.5 +/- 8.0 vs 35.5 +/- 17.9 min), the average flow rate of drugs (6.0 +/- 2.2 mg/kg/hr vs 6.7 +/- 2.4 microgram/kg/hr) has no significant difference between two groups. CONCLUSIONS: A single continuous infusion of propofol is applied as one of general anesthesia methods with O2-N2O, muscle relaxants. Propofol has a appropriate and similar analgesic effect compared with fentanyl in operation of little hemodynamic changes and short operation, and rapid recovery compared with fentanyl.

A Study in the Comparison of Body Temperature Change between General Anesthesia and Epidural Anesthesia / 대한마취과학회지

BACKGROUND: Core hypothermia after induction of anesthesia results from an core-to-peripheral redistribution of body heat and a loss of body heat to environment. The purpose of this study is finding body temperatures during operation by either general of epidural anesthesia and evaluates content of total body heat. METHODS: We measured tympanic membrane temperature, 4 point skin temperature (mid calf, mid thigh, upper extremity, nipple). And we calculate mean skin temperature, mean body temperature, total body heat content changes based on tympanic membrane temperature and 4 point skin temperature. RESULTS: Tympanic membrane temperature of the first group decreased significantly after 10 minutes of induction (p<0.005), the second group decreased after 45 minutes of induction. Although upper extremity temperature has continuously increased as time passed, there was no significant difference in both group. Lower extremity temperature has significantly increased after 30 minutes of induction in the first group, and the second group has significantly increased after 10 minutes of induction (p<0.05). Mean skin temperature hasdecreasd temperaturily in both group after 10 minutes of induction and increased as time passed. Mean body temperature of the first group has significantly decreased after 10 minutes of induction (p<0.05) and second group has no significant changes. Total body heat content has continuously decreased after induction with no significance. CONCLUSIONS: General anesthesia reveals more significant decrease than epidural anesthesia. Both groups show significant decrease of body temperature after induction. We think that we need to close attention to temperature changes after induction for preventing possible side effects due to core hypothermia.

The Effects of Trendelenburg Position and Intraabdominal CO2 Gas Insufflation on Cardiopulmonary System during Pelviscopic Surgery under General Anesthesia / 대한마취과학회지

BACKGROUND: Pelviscopic techniques have rapidly increased in therapeutic procedures as well as diagnostic procedures because of the many benefits associated with much smaller incisions than traditional open techniques. But the deliberate pneumoperitoneum with carbon dioxide during pelviscopic surgery may cause some problems-hypercarbia, pneumomentum, subcutaneous or mediastinal emphysema, pneumothorax, hypoxemia, hypotension, cardiovascular collapse and cardiac dysrhythmia. METHOD: We observed the changes of blood pressure (systolic, mean, diastolic), pulse rate, PaCO2, PaO2, peak inspiratory airway pressure and expired tidal volume at 10 minute after induction of general anesthesia (control value), 30 minutes and 60 minutes after insufflation of CO2 and Trendelenburg position. RESULTS: The blood pressure, PaCO2 and peak inspiratory airway pressure were increased significantly than control values (p<0.05). The changes of pulse rate and expired tidal volume were not statistically significant in comparison to control values. The PaO2 was decreased significantly (p<0.05). CONCLUSION: To minimize the risk of CO2 retension and unstability of cardiovascular system during pelviscopy under the Trendelenburg position, we must monitor the vital signs and the arterial blood gas status continuously and carefully.