Changes in prescribing patterns and resultant disease control after lamotrigine-related adverse drug reactions: A descriptive analysis

Purpose@#This study aimed to describe the desperate situation where the clinician should make decisions to further manage patients having experienced adverse drug reaction (ADR) to lamotrigine that is indicated to not easily controlled neuropsychiatric diseases. @*Methods@#A descriptive analysis was done by thoroughly reviewing medical records of patients who were reported to have ADR to lamotrigine in a regional drug-safety center between 2010 and 2018. @*Results@#Eighty-four cases of lamotrigine-related ADRs occurred in 80 patients. Skin lesions were most commonly observed in 70 cases (83.3%) and 14 cases (16.7%) had severe ADRs. Sixty-three subjects (78.8%) discontinued lamotrigine, while 17 (21.3%) continued it.At the time of discontinuation, 30.0% were prescribed aromatic antiepileptic drugs. Among 4 subjects who were eventually prescribed lamotrigine again after a period of discontinuation, 3 (75.0%) experienced its recurrence. Among patients who had taken alternative medications, the incidence of ADRs was higher in those being prescribed aromatic antiepileptic drugs than in the others being prescribed other than aromatic antiepileptic drugs (P = 0.013). Regarding the control of underlying diseases, as many as 65 (86.7%) and 68 (90.7%) failed to reach maintaining the resolved state from 6 months and 12 months after the substitution, respectively. @*Conclusion@#Patients can be easily trapped between the recurrence of ADRs and the treatment failure to a certain drug like lamotrigine, in which we can hardly find a reasonable alternative to manage them.

Successful Treatment of VancomycinResistant Enterococcus Bacteremia With a Combination of Daptomycin and Tigecycline in an Infant who Underwent Heart-Lung Transplantation

The treatment of invasive infections caused by multidrug-resistant vancomycin-resistant enterococci (VRE) is challenging, particularly in pediatric patients with underlying medical conditions. Newer antibiotics used to treat VRE infections in pediatric patients are insufficiently studied. This report presents the case of a 6-month-old infant who underwent heart–lung transplantation and was successfully treated with a combination of daptomycin and tigecycline for recurrent VRE bacteremia shortly after the discontinuation of linezolid.

Incidences and Prognostic Impact of c-KIT, WT1, CEBPA, and CBL Mutations, and Mutations Associated With Epigenetic Modification in Core Binding Factor Acute Myeloid Leukemia: A Multicenter Study in a Korean Population

BACKGROUND: To identify potential molecular prognostic markers in core binding factor (CBF) AML, we analyzed incidences and prognostic impacts of mutations in c-KIT, WT1, CEBPA, CBL, and a number of epigenetic genes in CBF AML. METHODS: Seventy one and 21 AML patients with t(8;21) and inv(16) were enrolled in this study, respectively. NPM1, CEBPA, c-KIT, IDH1/2, DNMT3A, EZH2, WT1, and CBL mutations were analyzed by direct sequencing. Patients were categorized with respect to c-KIT and WT1 mutation status, and both clinical features and prognoses were compared. RESULTS: The incidences of FLT3 internal tandem duplication (ITD), NPM1, CEBPA, IDH1/2, DNMT3A, EZH2, and CBL mutations were low (< or =5%) in CBF AML patients. However, c-KIT and WT1 mutations occurred frequently (10.9% and 13.8%, respectively). t(8;21) patients with c-KIT mutations showed significantly shorter overall survival (OS) and disease free survival (DFS) periods than those without mutations (P<0.001, for both); however, although the limited number of t(8;21) patients were analyzed, WT1 mutation status did not affect prognosis significantly. Relapse or death during follow-up occurred more frequently in t(8;21) patients carrying c-KIT mutations than in those without the mutation, although the difference was significant only in a specific patient subgroup with no WT1 mutations (P=0.014). CONCLUSIONS: The incidences of mutations in epigenetic genes are very low in CBF AML; however, c-KIT and WT1 mutations occur more frequently than others. The poor prognostic impact of c-KIT mutation in t(8;21) AML patients only applies in a specific patient subgroup without WT1 mutations. The prognostic impact of WT1 mutation in CBF AML is not evident and further investigation is required.

Risk-Reducing Genetic Variant of Wilms Tumor 1 Gene rs16754 in Korean Patients With BCR-ABL1-Negative Myeloproliferative Neoplasm

The genetic variant rs16754 of Wilms tumor gene 1 (WT1) has recently been described as an independent prognostic factor in AML patients. It is of great interest to test whether WT1 single nucleotide polymorphism can be used as a molecular marker in other types of cancer, to improve risk and treatment stratification. We performed sequencing analysis of exons 7 and 9 of WT1, which are known mutational hotspots, in a total of 73 patients with BCR-ABL1-negative myeloproliferative neoplasm (MPN) and 93 healthy controls. No previously reported WT1 mutations were identified in the present study. In Korean patients with BCR-ABL1-negative MPN, WT1 genetic variant rs16754 had no significant impact on clinical outcomes. We observed a significant difference in the allelic frequencies of WT1 rs16754 in Koreans between BCR-ABL1-negative MPN cases and healthy controls. Individuals carrying variant G alleles of WT1 rs16754 showed a relatively low prevalence of BCR-ABL1-negative MPN, compared with those carrying wild A alleles of WT1 rs16754 (Hazard ratio 0.10-0.65, P<0.05). Therefore, possession of the variant G allele of WT1 rs16754 may reduce the risk of developing BCR-ABL1-negative MPN.

A Case of Salivary-Type Amylase-Producing Multiple Myeloma Presenting as Mediastinal Plasmacytoma and Myelomatous Pleural Effusion

No abstract available.

Comparison of Methylation Profiling in Cancerous and Their Corresponding Normal Tissues from Korean Patients with Breast Cancer

BACKGROUND: Aberrant DNA hypermethylation plays a pivotal role in carcinogenesis and disease progression; therefore, accurate measurement of differential gene methylation patterns among many genes is likely to reveal biomarkers for improved risk assessment. We evaluated the gene hypermethylation profiles of primary breast tumors and their corresponding normal tissues and investigated the association between major clinicopathological features and gene hypermethylation. METHODS: A single reaction using methylation-specific multiplex ligation-dependent probe amplification was used to analyze the DNA methylation status of 24 tumor suppressor genes in 60 cancerous tissues and their corresponding normal tissues from patients with primary breast cancer. RESULTS: In cancerous breast tissues, 21 of 24 genes displayed promoter methylation in one or more samples. The most frequently methylated genes included RASSF1 (43.3%), APC (31.7%), CDKN2B (25.0%), CDH13 (23.3%), GSTP1 (16.7%), and BRCA1 (10%). APC was associated with lymph node metastasis, and BRCA1 was associated with negative estrogen receptor and negative progesterone receptor expression. In normal breast tissues, 8 of 24 tumor suppressor genes displayed promoter hypermethylation; CDKN2B (28.3%) and RASSF1 (8.3%) hypermethylation were most frequently observed. CONCLUSIONS: RASSF1 and CDKN2B hypermethylation in Korean breast cancer patients were the most frequent in cancerous tissue and corresponding normal tissue, respectively. Our data indicates that methylation of specific genes is a frequent event in morphologically normal breast tissues adjacent to breast tumors as well as the corresponding breast cancers. This study also suggests that gene methylation is linked to various pathological features of breast cancer; however, this requires confirmation in a larger study.

A Case of Partial Trisomy 20p Resulting from Meiotic Recombination of a Maternal Pericentric Inversion

Here we report the cytogenetic and clinical manifestations observed in a patient with a rec(20)dup(20p)inv(20)(p11.2q13.3)mat. The patient was a full-term newborn girl with asymmetric intrauterine growth restriction and multiple congenital malformations, including a ventricular septal defect, pulmonary atresia, ambiguous genitalia, clinodactyly, and sacral dimpling. To our knowledge, this is the 4th report in the world and the 1st one in Korea of a patient with rec(20)dup(20p).

Antimicrobial Susceptibility Patterns of Legionella isolates in the Environment and in Patients / 대한진단검사의학회지

BACKGROUND: Antimicrobial susceptibility of Legionella spp. has rarely been studied in Korea. Therefore, we aimed to determine the susceptibility of Legionella spp. to various antibiotics. METHODS: We assessed the antimicrobial susceptibility of 66 environmental and clinical Legionella isolates collected between January 2001 and December 2008 from Korea and Japan. The minimum inhibitory concentrations (MICs) of 6 antibiotics, namely, azithromycin, ciprofloxacin, clarithromycin, clindamycin, gatifloxacin, and gemifloxacin were determined by the broth microdilution method using buffered starch yeast extract broth. RESULTS: The MIC ranges of the 6 antibiotics used against the Legionella isolates were as follows: 0.004-0.062 microgram/mL (azithromycin), 0.002-0.5 microgram/mL (ciprofloxacin), 0.004-0.5 microgram/mL (clarithromycin), 0.12-4 microgram/mL (clindamycin), 0.002-0.12 microgram/mL (gatifloxacin), and 0.008-1 microgram/mL (gemifloxacin). CONCLUSIONS: Legionella spp. isolates from Korea and Japan were most susceptible to gatifloxacin. Azithromycin, clarithromycin, ciprofloxacin, and gemifloxacin were also effective for treating legionellosis.

Evaluation of ARCHITECT HCV Core Antigen Assay / 대한진단검사의학회지

BACKGROUND: Hepatitis C virus (HCV) core antigen (Ag) levels are known to be well correlating with HCV RNA levels, and may be used as an alternative marker of HCV replication for monitoring the response to HCV treatment. However, the low sensitivity of HCV core Ag assay has been an obstacle for clinical use. In this study, recently developed ARCHITECT HCV Ag assay (Abbott Laboratories, USA) was evaluated for analytical performance and clinical usefulness. METHODS: A total of 109 sera from HCV infected patients including various genotypes of HCV (1b, 2, 2a/2c, 2b, and 3a) and 20 sera from healthy donors were used for evaluating the sensitivity, precision, and linearity of the HCV core Ag assay. The cross reactivity with HIV, hepatitis B virus and myeloma proteins (N=5, each) and correlation with HCV RNA PCR assay were also evaluated. RESULTS: The sensitivity of the HCV core Ag assay was 97.2% (106/109) and there were no false positive results and cross reactivity. The within-run, between-run and between-day CVs were 3.0%, 2.5% and 3.0%, respectively. The levels of HCV core antigen showed a good correlation with those of HCV RNA quantification (r=0.940). The HCV Ag assay showed an excellent linearity in the range from 0.63 to 17,114 fmol/L (r=0.999). CONCLUSIONS: The ARCHITECT HCV Ag assay was good in sensitivity, precision, and linearity and its results well correlated with HCV RNA levels. This assay could be used as a good marker of viral replication for monitoring the therapy response in chronically HCV infected patients.

ERRATUM / 대한진단검사의학회지

No abstract available.

Comparison of the Frequencies and Distributions of Unexpected Antibodies Based on Different Calculation Criteria / 대한진단검사의학회지

BACKGROUND: The frequencies and distributions of unexpected antibodies have been reported using two different criteria, based on either number of persons tested or number of tests performed. But there has been no study that compared the results of analyses based on these two different criteria using the same data set. METHODS: Unexpected antibody tests performed in a University Hospital during recent 6 yr (January 2002-December 2007) were retrospectively analyzed: 76,985 tests (59,503 persons) for screening and 875 tests (749 persons) for identification. Data were analyzed using two different criteria, based on 'persons tested' and 'tests performed'. Antibodies had been screened and identified using LISS/Coombs gel cards with DiaMed-ID system (DiaMed AG, Switzerland). RESULTS: Frequencies of unexpected antibodies based on 'persons tested' and 'tests performed' were 1.32% and 1.34%, respectively (P=0.88). For frequently detected as well as rarely detected antibodies, there were no significant differences in the frequencies based on two different criteria. However, for rarely detected antibodies (anti-Xg(a) and Anti-E & D), the frequencies based on 'tests performed' were higher than those based on 'persons tested', affecting a change in the order of frequencies of antibodies detected. CONCLUSIONS: As there were no significant differences in the frequencies of unexpected antibodies calculated using two different criteria, both criteria can be used together for the patient population in our hospital. However, two criteria should be compared to validate the results for other populations.