Once-daily dosing of amikacin for treatment of Mycobacterium abscessus lung disease.

SETTING: Tertiary referral centre, Samsung Medical Center, South Korea. OBJECTIVE: To evaluate the pharmacokinetic parameters and toxicities of once-daily amikacin (AMK) dosing for lung disease due to Mycobacterium abscessus. DESIGN: A retrospective review of 48 patients with M. abscessus lung disease who received once-daily AMK for 4 weeks between January 2012 and June 2015. RESULTS: With a starting dose of 15 mg/kg/day and adjustment of AMK dose according to the peak serum level (Cmax), the Cmax target of 55-65 µg/ml was achieved in 31.3% (15/48) of patients in the first week, 68.8% (33/48) in week 2, 91.7% (44/48) in week 3 and 95.8% (46/48) in week 4. Transient nephrotoxicity developed in 6.3% (3/48) of patients and ototoxicity in 25.0% (6/24), which was determined by audiogram as hearing loss, asymptomatic in five patients and tinnitus in one. Multivariate analysis revealed that the highest drug concentration 12 h after administration was significantly associated with the development of toxicities (adjusted odds ratio 1.862, P = 0.047). CONCLUSION: Our results suggest that once-daily AMK for 4 weeks with a target Cmax of 55-65 µg/ml can be used in patients with M. abscessus lung disease, with careful monitoring of toxicity.

Comparison of 3D and 2D shear-wave elastography for differentiating benign and malignant breast masses: focus on the diagnostic performance.

AIM: To evaluate the diagnostic performance of three-dimensional (3D) image shear-wave elastography (SWE) for differentiating benign from malignant breast masses compared to two-dimensional (2D) SWE and B-mode ultrasound (US). MATERIALS AND METHODS: This study consisted of 205 breast lesions from 199 patients who underwent B-mode US and SWE before biopsy from January 2014 to March 2016. Quantitative elasticity values (maximum and mean elasticity, Emax and Emean) obtained from 2D and 3D SWE (axial, sagittal, and coronal images) were reviewed retrospectively, in addition to the histopathological findings including immunohistochemistry profiles (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer) in cases of malignancy. Histopathological findings were regarded as the reference standard. The diagnostic performance of each data set was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) analysis to compare sensitivity and specificity. RESULTS: Among 205 lesions, 105 (51.22%) were malignant and 100 (48.78%) were benign. Compared to benign masses, malignant masses had higher values of Emax and Emean on both 2D and 3D SWE, the differences of which were statistically significant (p<0.001). The AUCs of 2D, 3D axial, and sagittal SWE were significantly higher than that of 3D coronal SWE (p<0.05). In addition, the sensitivities of axial, sagittal, and coronal 3D SWE were all higher than that of 2D SWE for Emean (81.9%, 87.6%, and 89.5% versus 70.5%, respectively, p<0.05). Conversely, the specificity of 2D and 3D axial SWE was higher than that of 3D sagittal and coronal SWE (Emax, 84%, 83% versus 76%, 73%; Emean, 85%, 81% versus 68%, 50%, respectively, p<0.05). We also assessed changes in Breast Imaging-Reporting and Data System (BI-RADS) category 3 and category 4a lesions by adding each of the parameters for 2D and 3D SWE in B-mode US. The specificity, PPV, and accuracy of combined 2D or combined 3D SWE with B-mode US was statistically higher than that of B-mode US alone for differentiating benign and malignant lesions (p<0.05). CONCLUSIONS: Among SWE images, 2D SWE, and 3D SWE axial and sagittal images exhibited superior diagnostic performance compared to 3D coronal images. Addition of 3D SWE images to B-mode US improved the diagnostic performance for distinguishing benign from malignant masses.

Differentiation of benign and metastatic axillary lymph nodes in breast cancer: additive value of MRI computer-aided evaluation.

AIM: To retrospectively determine the qualitative and quantitative cut-off values of the magnetic resonance computer-aided evaluation (MR CAE) parameters to differentiate between benign and metastatic axillary lymph nodes (ALNs) and to investigate the combined diagnostic performance of MR CAE imaging. MATERIALS AND METHODS: From July 2011 to June 2014, 124 patients who underwent preoperative conventional MR, diffusion-weighted (DW), and MR CAE imaging were included. Computer-generated qualitative and quantitative features for ALNs were recorded, and two breast imaging radiologists interpreted the MR images for the presence of metastatic ALNs using conventional MR and DW, and in combination with MR CAE images by consensus. The cut-off values of MR CAE and diagnostic performance were derived from the receiver operating characteristic (ROC) curve. RESULTS: Thirty-four (26.4%) were ALN positive and 90 (73.6%) were ALN negative on the final histopathological result. On qualitative analysis, visualization on the colour map (p=0.007) and kinetic curve type (p<0.001) were significantly different between the groups. On quantitative analysis, mean values (%) of persistent, plateau, and washout ratios differed significantly (p<0.001). Of these significant parameters, a washout ratio of >49% showed the greatest diagnostic accuracy (area under the ROC curve, 0.909). With conventional MR and DW images, sensitivity, specificity, and accuracy were 82.4%, 85.6%, and 84.7%, respectively. With added information from MR CAE images, accuracy significantly improved to 93.5% (p=0.043). The sensitivity and specificity improved to 91.2% (p=0.403) and 94.4% (p=0.086), respectively. CONCLUSION: The additive use of MR CAE improved diagnostic performance and can be helpful for differentiating benign from metastatic ALNs.

Impact of preoperative bilateral whole breast sonography in patients with invasive lobular carcinoma: results from two medical centers.

PURPOSE: The purpose of this study was to evaluate the sensitivity of bilateral whole breast sonography (BWBS) combined with mammography for the detection of additional lesions, as well as index lesions, in patients with invasive lobular carcinoma (ILC) and to evaluate the impact of BWBS on surgical treatment and cancer staging strategies. MATERIALS AND METHODS: We retrospectively reviewed mammographic and sonographic records of 97 patients with proven ILCs between November 2002 and November 2009. We evaluated the sensitivity of mammography and BWBS for the detection of additional and index lesions. We compared the impact of BWBS on surgical treatment and breast cancer staging between cases with single index lesions and with BWBS-detected additional lesions and index lesions. We compared the differences in sensitivity, surgical treatment procedures and breast cancer staging between BWBS and MRI confined to the patients underwent MRI. RESULTS: The overall sensitivity was 74.4% (93/125 lesions) for mammography and 96.0% (120/125 lesions) for BWBS (p < 0.001). The group with additional lesions detected using US alone exhibited more frequent mastectomy (p = 0.003) and higher N staging (p = 0.051) than did the group with single index lesions. Comparing the BWBS and MRI cases, there were no significant differences in lesion staging, the sensitivity of malignant foci detection (p = 0.074). CONCLUSION: BWBS has a higher sensitivity than does mammography for the detection of index and additional ILC. Detection of additional malignancies using BWBS could affect which strategy is chosen for surgical treatment.

Immunizing children to protect against the increasing risk of hepatitis A in adolescents and young adults in South Korea.

We evaluated the CR326F strain (VAQTA) derived hepatitis A vaccine in Korean children and adolescents >2 years of age to consider a future immunization program. In our study, the pediatric two-dose regimen of VAQTA was found to be generally well tolerated and resulted in 100% (95% CI 94.8, 100.0) seroconversion after 2 doses. Immunizing children with the HAV vaccine routinely should be considered in South Korea, particularly in areas where recent outbreaks have occurred.

Efficacy of single-dose SA 14-14-2 vaccine against Japanese encephalitis: a case control study.

BACKGROUND: In China, since 1989, an estimated 120 million children have been immunised with the SA 14-14-2 live-attenuated Japanese encephalitis (JE) vaccine at ages 1, 2, and 6 years. A case-control study of licensed vaccine found two doses to be 98% effective. Subsequently, researchers found that single-dose vaccine efficacy was high; we aimed to confirm this result. METHODS: During July 11-24, 1999, 160000 doses of JE vaccine were given to children aged 1-15 years, resident in three districts of Nepal. Several cases of JE were admitted to hospital from early August. We obtained names and addresses of cases with serological evidence of a recent infection from Bheri Zonal Hospital, Nepalgunj. We did a matched case-control study and calculated the odds ratio of vaccination among JE cases and age-sex matched village controls. FINDINGS: 20 children, aged 1-15 years, were identified whose illness conformed with the JE case definition and were resident in villages receiving the vaccine. None of 20 JE cases had received JE vaccine compared with 326 of 557 age-sex matched village controls. The efficacy of a single dose of JE vaccine was 99.3% (CI 94.9-100%). INTERPRETATION: A single dose of JE vaccine is highly efficacious in preventing Japanese encephalitis when administered only days or weeks before exposure to infection.

Primary humoral immune responses to formalin inactivated hemorrhagic fever with renal syndrome vaccine (Hantavax): consideration of active immunization in South Korea.

The efficacy of a formalin-inactivated hemorrhagic fever with renal syndrome (HFRS) vaccine and the effectiveness of a related vaccination program have not been previously evaluated. We measured the primary immune responses to Hantavax by plaque reduction neutralizing antibody test (PRNT), hemagglutination inhibition test (HAI), ELISA and high density particle agglutination test (HDPA) in order to confirm a possible biological efficacy through independent substantiation of experimental results and to compare the results with previous studies. Following two doses of primary vaccination, the seroconversion rate of PRNT and HAI antibody was 33.3% (10/30) [95% C.I. 17.3-52.5%] and 26.7% (8/30) [95% C.I. 12.3-45.9%], respectively. The correlation between PRNT and HAI antibody showed a statistical significance (r=0.58, p<0.01). The seroconversion rate of HDPA and ELISA were both 76.7% (23/30) [95% C.I. 57.7-90.1%], which correlated well with each other (r=0.58, p<0.01). In our study, Hantavax elicited low neutralizing antibody responses, at least in the volunteers samples that we tested. The vaccination program, including the vaccine itself, that has been adopted by the national immunization program to protect against HFRS in Korea should be re-evaluated and re-formulated to produce a higher protective immune response rate.

The changing epidemiology of hepatitis A in children and the consideration of active immunization in Korea.

Currently, Korea is a low endemicity country for HAV, especially in children. However, recent reports of hepatitis A outbreaks show that there has been a shift of disease incidence to adolescents and young adults, with 2 cases of acute liver failure in one reported outbreak. We need to study the immune status for HAV in order to provide information for the establishment of preventive measures and possible consequences of HAV in Korea. A total of 334 infants, children and adolescents less than 20 years of age living in rural areas of Kyonggi Province, Korea were evaluated for anti-HAV immune status in 1996. Five hundred and eighty-four primary school children living in the same area were separately evaluated for the natural seroconversion rate between 1993 and follow-up samples taken in 1996. Anti-HAV IgG antibody was measured by enzyme immunoassay (HAVAB EIA kit, Abbott Laboratories, Chicago, Illinois, USA). In comparison with previous reports of seroprevalence rates, our data confirmed a dramatic drop in seroprevalence rates among children and adolescents under 20 years of age living in rural areas, from over 63.8% two decades ago to 4.6% in 1996. Natural acquisition of HAV antibody in primary school children rarely occurs, registering only 0.5% during three years. Several outbreaks in young adults during 1996-1998 suggested that immunity against HAV in this population is so low that massive outbreaks are unavoidable. Teenagers and young adults, especially soldiers, who are likely to be exposed to contaminated food or water, would also have a greater risk of hepatitis A. Immunizing children with HAV vaccine as a routine schedule should also be considered in Korea in the future, particularly if the disease burden could be estimated and the cost-effectiveness of the vaccine could be proved.

Japanese encephalitis immunization in South Korea: past, present, and future.

Japanese encephalitis (JE), once a major public health problem in South Korea, has declined since the 1980s, as a result of improved living conditions, a mosquito eradication program, and a national JE vaccination program, which includes annual booster vaccine for all children less than or equal to 15 years of age. Increased immunity has greatly reduced illness and death; however, vaccine adverse effects are increasing, and a National Compensation Program for Vaccine Injury was begun in 1995. This article reviews past successes, current problems, and future direction of the JE vaccination program in South Korea.

Primary and booster immune responses to SA14-14-2 Japanese encephalitis vaccine in Korean infants.

Attenuated SA14-14-2 Japanese encephalitis (JE) vaccine has been administered safely and effectively to more than 100 million children in China since 1988 and recently, licensure of the vaccine in Korea has been sought. In the first clinical evaluation of the vaccine outside of China, we monitored side effects in 84 children and evaluated antibody responses to a single dose given as primary JE vaccination in 68 children, 1-3 years old (mean age 27 months). No significant adverse events were noted. Neutralizing antibodies (geometric mean titer [GMT] of 188) were produced in 96% of the 68 subjects. In 10 other children who previously had been immunized with two or three doses of inactivated JE vaccine, the booster administration of SA14-14-2 vaccine produced an anamnestic response in all, with a GMT of 3378. In a comparison group of 25 children previously immunized with two doses of inactivated vaccine, neutralizing antibody titers were detected in 16 (64%). Viral specific IgM was detected in nine primary vaccinees (13%) but in others, IgM may have declined to undetectable levels in the four week postimmunization sample. Live attenuated SA14-14-2 JE vaccine is a promising alternative to the only commercially available JE vaccine for national childhood immunization programs in Asia.

The causative organisms of bacterial meningitis in Korean children, 1986-1995.

Bacterial meningitis remains a serious cause of morbidity and mortality in childhood. Epidemiologic investigations have shown variability in disease risks among different populations and races. In Korea, however, basic epidemiologic information on bacterial meningitis in children is limited. The main purpose of this study was to analyze bacteriologically proven meningitis cases in terms of the relative frequency of causative organisms, mortality rate, and age distribution beyond the neonatal period. Data was obtained from the hospital records who had been diagnosed with bacterial meningitis at 13 general or university hospitals from 1986 through 1995. The patients had at least one positive CSF culture for bacteria. Of 140 cases of CSF culture-proven bacterial meningitis, 46.4% was < or =1 year, 62.1% was < or =2 years, 81.4% was < or =5 years cumulatively. Streptococcus pneumoniae was the most common bacteria responsible for 48 (35.0%) of all cases regardless of age, followed by Haemophilus influenzae for 48 (34.3%) and Neisseria meningitidis for 8 (6.4%) patients. The case fatality rate was 20.0%, 17.1%, and 16.7% for N. meningitidis, S. pneumoniae, and H. influenzae, respectively. In conclusion, the most common organisms of culture-proven bacterial meningitis in the last 10 years have been S. pneumoniae, H. influenzae, and N. meningitidis in order of frequency. Further study should be extended to nation-wide epidemiologic evaluation to show the incidence of bacterial meningitis caused by these three important organisms.

Use of vaccine in the era of antimicrobial resistance: need of effective pneumococcal vaccines.

Streptococcus pneumoniae is an important pathogen causing invasive infections particularly in children. Penicillin-nonsusceptible pneumococci are very prevalent in Korea and a difficult problem in antimicrobial treatment. Immunization with effective vaccines including viral and bacterial vaccines has proven to be the most effective and reliable method to prevent the target disease. Universal immunization to infants with Haemophilus influenzae type b conjugate vaccine has dramatically proven to be very effective in reducing invasive Hib diseases and also the carriage rate. The 23-valent pneumococcal polysaccharide vaccine is effective in preventing invasive diseases in young adults and covers most of the penicillin-nonsusceptible types. It has not proven very effective in the prevention of otitis media, and is unable to elicit adequate antibody response in children younger than 2 years of age. Recently a new polysaccharide-protein conjugate vaccine was developed which can elicit antibody response in children younger than 2 years of age. However, the vaccine is only 8-valent at the moment. Studies are required to determine the possible idiotypic modulation and nonproductive immune response when polysaccharide vaccine is administered to infants. Part of the problem of antimicrobial-resistant pneumococcal infection may be solved in the future with the use of improved vaccine. Preventing pneumococcal infections with safe and effective vaccines will not only reduce the development of antibiotic resistance, but could also be the most cost-effective method to control pneumococcal disease.

Congenital cytomegalovirus infection in Korean population with very high prevalence of maternal immunity.

In order to asses congenital cytomegalovirus (CMV) infection in Korea, five hundred and seventy five pregnant women (mean age 29.5 +/- 3.8 yrs., mean gestational age at test 37.5 +/- 6.7 weeks) visiting the prenatal clinic at Severance Hospital, Seoul, Korea were studied. CMV IgG antibody was present in 96% (552/575) and IgM antibody was present in 0.7% (4/575) of the pregnant women by the third trimester. Four of 445 cord sera were positive for CMV IgM antibody (0.9%). Urine samples from 514 newborns were tested for the evaluation of congenital CMV infection. Six (1.2%) of 514 newborns excreted CMV in their urine. All the congenitally infected infants had subclinical involvement at birth and during the 12 months of the follow-up period. These results indicate that Korean pregnant women were highly immunized against CMV by the third trimester. Furthermore this study suggests that the rate of congenital CMV infection is relatively as high as rates previously reported from other countries, although there is a very high prevalence of maternal immunity. The incidence of maternal primary infection during pregnancy seems to be rare and therefore most congenital infections in Korea might be following by maternal reactivation or reinfection.

Cytomegalovirus infection in sexually active adolescents.

To determine whether cytomegalovirus (CMV) infection in teenage girls is related to sexual activity, 254 girls 12-18 years old (mean, 15.8) attending a contraceptive counseling clinic were studied. Participants were screened for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis, and serum antibody to CMV was determined. Demographic and sexual history data were collected by interview. The mean number of lifetime sex partners was 2.2; 173 (68%) were seropositive. Race, greater than 3 years of sexual activity, and greater than 2 lifetime sex partners were significant risk factors for CMV infection (odds ratios [OR], 1.8-4.7; P less than .05). Using logistic regression analysis, a composite sexual activity variable was the most important risk factor for CMV infection (OR, 4.8; P = .003), followed by race (OR, 3.4; P = .004) and a sexually transmitted disease composite variable (OR, 2.4; P = .016). Sexual activity is an important risk factor for CMV infection in adolescent girls.