Misuk Ji

Acute Cholecystitis in Patients with Scrub Typhus

Acute cholecystitis is a rare complication of scrub typhus. Although a few such cases have been reported in patients with scrub typhus, the clinical course is not well described. Of 12 patients, acute cholecystitis developed in 66.7% (8/12) of patients older than 60 yr. The scrub typhus group with acute cholecystitis had marginal significant longer hospital stay and higher cost than the group without cholecystitis according to propensity score matching. Scrub typhus should be kept in mind as a rare etiology of acute cholecystitis in endemic areas because the typical signs of scrub typhus such as skin rash and eschar can present after the abdominal pain.

Determination of high-sensitivity cardiac troponin I 99th percentile upper reference limits in a healthy Korean population

OBJECTIVES This study aimed to determine the 99th percentile upper reference limit (URL) concentration of cardiac troponin I (cTnI) with a high-sensitivity assay in a Korean population. DESIGN AND METHODS Cardio-healthy males and females were enrolled between March 2014 and March 2015. Participants with possible subclinical conditions were excluded on the basis of laboratory measures (primary: estimated glomerular filtration rate and glycated hemoglobin; secondary: B-type natriuretic peptide). Serum cTnI was measured using ARCHITECT STAT High-Sensitive Troponin-I Assay (Abbott Diagnostics, USA). RESULTS A total of 1204 participants completed a self-reporting questionnaire for inclusion in the study. Of these, we excluded 349 (29.0%) participants on the basis of primary (n=283) and secondary (n=66) laboratory measures. Ultimately, we included 854 participants (mean age, 49.8±10.2years) in the final analysis. The 99th percentiles of cTnI concentrations were 18 (90% confidence interval [CI], 14-35) ng/L for all participants, 20 (90% CI, 15-69) ng/L for males and 19 (90% CI, 11-41) ng/L for females. In both males and females, the median cTnI concentrations were significantly higher in participants aged 50years and older than in those younger than 50years old. CONCLUSIONS In this study, the reference population with Korean ethnicity had lower overall and male 99th percentile URLs than other reference populations. Our data suggest that 99th percentile URLs may be influenced by factors such as ethnicity, age distribution of participants, and selection criteria used to define a healthy reference population.

The 99th percentile values of six cardiac troponin assays established for a reference population using strict selection criteria

BACKGROUND Since the 99th percentile reference limit for cardiac troponin (Tn) can vary depending on the reference population, Sandoval et al. published systematic selection criteria. In this study, these systematic criteria were applied for the first time to obtain the 99th percentile reference limits for 6 Tn tests. METHODS The reference population was selected in accordance with the systematic criteria, and reference limits were set with respect to the six types of Tn assays. The coefficient of variation (CV) at the reference limit was determined using 3-4 concentrations of frozen serum. RESULTS In total, 641 South Koreans (303 males, 338 females) were selected as the reference population. The 99th percentile reference limit of Tn in the six assays ranged from 13.4 to 34.2pg/ml. The measurable fractions among the reference population ranged from 1.3% to 80.5%. The CVs at the reference limit ranged from 5.3% to 43.0%, and three were <10%. CONCLUSIONS In this study, a reference population was selected for the first time in accordance with the systematic criteria of Sandoval et al., and the reference limit for South Koreans was established. The values obtained in this study are different from those proposed by manufacturers, which confirms the importance of having a reference population. Four out of six assays did not fulfill the criteria for high-sensitivity tests.

Genetic Polymorphism of CYP2D6 and Clomiphene Concentrations in Infertile Patients with Ovulatory Dysfunction Treated with Clomiphene Citrate

CYP2D6 is primarily responsible for the metabolism of clomiphene citrate (CC). The purpose of the present study was to investigate the relationship between CYP2D6 genotypes, concentrations of CC and its major metabolites and drug response in infertility patients. We studied 42 patients with ovulatory dysfunction treated with only CC. Patients received a dose of 100 mg/day CC on days 3-7 of the menstrual cycle. CYP2D6 genotyping and measurement of CC and the major metabolite concentrations were performed. Patients were categorized into CC responders or non-responders according to one cycle response for the ovulation. Thirty-two patients were CC responders and 10 patients were non-responders with 1 cycle treatment. The CC concentrations were highly variable within the same group, but non-responders revealed significantly lower (E)-clomiphene concentration and a trend of decreased concentrations of active metabolites compared to the responders. Nine patients with intermediate metabolizer phenotype were all responders. We confirmed that the CC and the metabolite concentrations were different according to the ovulation status. However, our results do not provide evidence for the contribution of CYP2D6 polymorphism to either drug response or CC concentrations.

Usefulness of plasma neutrophil gelatinase-associated lipocalin as an early marker of acute kidney injury after cardiopulmonary bypass in Korean cardiac patients: A prospective observational study

OBJECTIVES Development of acute kidney injury (AKI) after cardiopulmonary bypass (CPB) is relatively common and associated with increased mortality. Recently, plasma neutrophil gelatinase-associated lipocalin (NGAL) was used for the prediction of AKI. We evaluated the clinical usefulness of plasma NGAL. DESIGN AND METHODS One hundred twelve adult patients undergoing cardiovascular surgery with CPB were included. Blood samples were obtained at baseline, at intensive care unit (ICU) admission, and 24h after ICU admission. The development of AKI, which is defined as an increase in serum creatinine by more than 50% within 3 postoperative days, was monitored. NGAL levels were analyzed by a Biosite Triage meter (Alere Medical, USA). Diagnostic performance of NGAL was analyzed using the area under the receiver operating characteristic curve. RESULTS In AKI patients (n=13), plasma NGAL levels at ICU admission were significantly higher than those at baseline [177 (122-402) vs. 121 (74-158) ng/mL, median (interquartile range), p=0.028], whereas serum creatinine showed no significant change. The predictive value of NGAL at ICU admission was 0.812 [95% confidence interval (CI), 0.68 to 0.95] with a cut-off value of 168.5ng/mL (sensitivity, 61.5%; specificity, 88.9%). After the exclusion of 35 patients with preoperative decreased renal function, the predictive value was increased to 0.911 (95% CI, 0.82 to 1.00). CONCLUSIONS This study showed that plasma NGAL may serve as a useful biomarker for the early detection of AKI in adult patients following CPB.

Abrupt thrombocytopenia with sustained trilineage engraftment in a stem cell transplant recipient.

Sir, Thrombocytopenia is a common presentation in myelodysplastic syndrome (MDS) and also a significant complication occurring after stem cell transplantation [1, 2]. During work-up of thrombocytopenia, immune thrombocytopenia (ITP) should be considered as a differential diagnosis, which may occur in isolation or in association with other disorders [3]. Secondary ITP comprises 20% of all ITP cases and, rarely, it can occur after allogeneic stem cell transplantation [3, 4]. We describe a patient who presented with abrupt thrombocytopenia on day +180 after allogeneic stem cell transplantation for MDS under full donor chimerism status. In May 2014, a 33-year-old man presented with oneday history of generalized petechiae. His blood pressure, pulse rate, temperature, and respiration rate were all within normal ranges. Splenomegaly was found with abdominal computed tomography. His complete blood count on admission was as follows: 16.5 g/dL hemoglobin; 4.09 9 10/L white blood cells; and 2 9 10/L platelet counts. Coagulation test (prothrombin time and activated partial thromboplastin time) and D-dimer results were unremarkable. He had been diagnosed with MDS, refractory cytopenia with multilineage dysplasia in December 2012 and treated with decitabine. His disease was progressive, and the blasts increased up to 13.0% on follow-up bone marrow examination in November 2013. He underwent allogeneic peripheral blood stem cell transplantation from unrelated donor in December 2013. Engraftment was successful with absolute neutrophil counts over 0.5 9 10/L on day +13. Trilineage regeneration of bone marrow and full donor chimerism with short tandem repeat analysis were confirmed on day +37. Trimethoprim-sulfamethoxazole was added to his medication regimen from 4 weeks before the thrombocytopenic attack. After admission on post-transplant day +180, from hospital day (HD) 1 to HD 4, he was refractory to repeated platelet transfusions with platelet counts less than 20 9 10/L, percentage immature platelet fraction (%-IPF) of 0%, and absolute IPF (A-IPF) of 0 9 10/L. On the bone marrow examination performed on HD 1, blasts were counted to 2.5%, and cellularity was 40%. There was no evidence of prominent dyshematopoiesis in megakaryocytes, granulocytic, and erythroid cells. CD34positive cells comprised 0.6% of total CD45-gated cells in flow cytometry, and chromosome analysis showed a normal karyotype. Full donor chimerism was documented with short tandem repeat analysis. Thus, normocellular marrow with trilineage regeneration was confirmed without evidence of relapse. PCR test for cytomegalovirus was negative. He started to receive high-dose corticosteroids from HD 1 and stopped the trimethoprim-sulfamethoxazole on HD 3. Intravenous immunoglobulin therapy was applied on HD 4 and HD 5. After that, the platelet count increased to 25 9 10/L, and %-IPF increased to 17.8% (reference range, 1.0–7.3%) on HD 5. But A-IPF was 0.2 9 10/L (reference range, 2.49–15.64 9 10/L) at this time. The reference ranges for %-IPF and A-IPF were established in our laboratory with Sysmex XN modular system [5]. Afterward, his platelet count was maintained between 15 9 10/L and 43 9 10/L during 2 weeks without complete recovery. He finally underwent splenectomy on HD 19, and his platelet count increased to 96 9 10/L on the next day of operation and reached 191 9 10/L with %-IPF of 6.3% after two weeks. A-IPF was normalized only after the splenectomy (Figure 1). Our patient presented with severe thrombocytopenia that occurred abruptly on post-transplant day +180. His thrombocytopenia was expected to be related to relapse of MDS initially, but his bone marrow showed adequate trilineage regeneration (megakaryocytic, granulocytic, and erythroid lineages). Although the platelet count increased after steroid therapy and discontinuation of trimethoprim-sulfamethoxazole, it maintained below 50 9 10/L without full recovery. The platelet count was normalized after splenectomy that was performed due to possibility of steroid-resistant ITP. It was also suspected that prophylactic administration of trimethoprim-sulfamethoxazole might be temporally associated with the thrombocytopenic onset, because the trimethoprim-sulfa-