Piperacillin-Tazobactam versus Cefotaxime as Empiric Treatment for Febrile Urinary Tract Infection in Hospitalized Children.

BACKGROUND: According to international pediatric urinary tract infection (UTI) guidelines, selecting ampicillin/sulbactam or amoxicillin/clavulanate is recommended as the first-line treatment for pediatric UTI. In Korea, elevated resistance to ampicillin and ampicillin/sulbactam has resulted in the widespread use of third-generation cephalosporins for treating pediatric UTIs. This study aims to compare the efficacy of piperacillin-tazobactam (TZP) and cefotaxime (CTX) as first-line treatments in hospitalized children with UTIs. MATERIALS AND METHODS: The study, conducted at Jeju National University Hospital, retrospectively analyzed medical records of children hospitalized for febrile UTIs between 2014 and 2017. UTI diagnosis included unexplained fever, abnormal urinalysis, and the presence of significant uropathogens. Treatment responses, recurrence, and antimicrobial susceptibility were assessed. RESULTS: Out of 323 patients, 220 met the inclusion criteria. Demographics and clinical characteristics were similar between TZP and CTX groups. For children aged ≥3 months, no significant differences were found in treatment responses and recurrence. Extended-spectrum beta-lactamase (ESBL)-positive strains were associated with recurrence in those <3 months. CONCLUSION: In Korea, escalating resistance to empirical antibiotics has led to the adoption of broad-spectrum empirical treatment. TZP emerged as a viable alternative to CTX for hospitalized children aged ≥3 months with UTIs. Consideration of ESBL-positive strains and individualized approaches for those <3 months are crucial.

A Personalized Cancer Vaccine that Induces Synergistic Innate and Adaptive Immune Responses.

To demonstrate potent efficacy, a cancer vaccine needs to activate both innate and adaptive immune cells. Personalized cancer vaccine strategies often require the identification of patient-specific neoantigens; however, the clonal and mutational heterogeneity of cancer cells presents inherent challenges. Here, extracellular nanovesicles derived from alpha-galactosylceramide-conjugated autologous acute myeloid leukemia (AML) cells (ECNV-αGC) are presented as a personalized therapeutic vaccine that activates both innate and adaptive immune responses, bypassing the need to identify patient-specific neoantigens. ECNV-αGC vaccination directly engages with and activates both invariant natural killer T (iNKT) cells and leukemia-specific CD8+ T cells in mice with AML, thereby promoting long-term anti-leukemic immune memory. ECNV-αGC sufficiently serves as an antigen-presenting platform that can directly activate antigen-specific CD8+ T cells even in the absence of dendritic cells, thereby demonstrating a multifaceted cellular mechanism of immune activation. Moreover, ECNV-αGC vaccination results in a significantly lower AML burden and higher percentage of leukemia-free survivors among cytarabine-treated hosts with AML. Human AML-derived ECNV-αGCs activate iNKT cells in both healthy individuals and patients with AML regardless of responsiveness to conventional therapies. Together, autologous AML-derived ECNV-αGCs may be a promising personalized therapeutic vaccine that efficiently establishes AML-specific long-term immunity without requiring the identification of neoantigens.

Role of 16S Ribosomal RNA Analysis in Identification of Microorganisms in Febrile Urinary Tract Infection of Infants.

OBJECTIVES: To assess the role of 16S ribosomal RNA analysis in microbial identification in febrile infants under six months of age diagnosed with UTI, and compare it with the conventional culture results. METHODS: Young infants under 6 mo of age who were suspected UTI from May 2018 to April 2019 had been enrolled. Uropathogens were analyzed by the traditional microbiologic culture system and the 16S rRNA analysis. The 16S rRNA analysis included 16S rRNA amplicon band confirmation and bacterial identification through the sequencing analysis. RESULTS: A total of 57 infants with the febrile UTI were enrolled, and the median age was 3 mo. Uropathogens were identified in 43 patients (75.4%) in a conventional culture method: Escherichia coli in 38 patients (88.4%), Klebsiella pneumoniae in 3 (7.0%), Enterobacter cloacae in 1 (2.3%), and Pseudomonas aeruginosa in 1 (2.3%). Fifty urine samples (87.8%) had positive 16S rRNA amplicon band on electrophoresis. Among the 16S rRNA-positive urines, 40 samples were available for the sequence analysis of 16S rRNA, and the identification of bacteria were as follows: E. fergusonii in 36, K. pneumoniae in 3, and Shigella flexneri in 1. The sensitivity of 16S rRNA sequencing was 81.4% [95% confidence interval (CI), 67.4-90.3%] and the specificity was 64.3% (95% CI, 38.8-83.7%). CONCLUSION: Uropathogen identification using 16S rRNA analysis could be applied to manage the febrile UTI in young infants clinically in combination with the conventional culture.

Accurate Mandible Reconstruction by Mixed Reality, 3D Printing, and Robotic-Assisted Navigation Integration.

ABSTRACT: Mandibular reconstruction is one of the most complex procedures concerning the patient's postoperative facial shape and occlusion condition. In this study, the authors integrated mixed reality, three-dimensional (3D) printing, and robotic-assisted navigation technology to complete the mandibular reconstruction in a novel and more accurate way. Mixed reality can visualize the significant anatomical structures of the operative area, but only be used in simulated operation by now. Three-dimensional printing surgical guide plate makes it easy to separate tissue, while imprecision often occurs due to the potential of displacement and deformation. In recent years, most robotic-assisted navigation surgery technology can only achieve precise position by 2D view on the screen but not realistic 3D navigation. in this study, the integrated 3 technologies were used in mandibular reconstruction. Preoperative imaging examination was performed, and the data were imported into the digital workstation before operation. First, the original data was edited and optimized to reconstruct the digital model and formulate the surgical plan. Then MR was used to output the visualized project and matched the 3D reconstruction model in reality. The 3D plate was printed for surgical guidance. Last, robotic-assisted navigation was used to guide and position the vascularized fibula autograft and the immediate dental implantation. In conclusion, the authors integrated the 3 technologies and constructed a new digital surgical procedure to improve surgical accuracy and simplify the procedure comparing with traditional surgery.

Characteristics and outcomes of patients screened by rapid response team who transferred to the intensive care unit.

BACKGROUND: The utilization of a rapid response team (RRT) has influenced the clinical outcomes of patients in the general ward. However, the characteristics of RRT-screened patients who are transferred to the intensive care unit (ICU) are unknown. Therefore, the present study aimed to evaluate these factors. METHODS: We conducted a retrospective study using patient data from a tertiary medical center in Republic of Korea between January 2016 and December 2017. Multivariate logistic regression analyses were performed to assess the factors associated with the risk of in-hospital mortality. RESULTS: A total of 1,096 patients were included: 389 patients were transferred to the ICU, and 707 patients stayed in the ward. Patients in the ICU group were more likely to be admitted for medical reasons, hepatobiliary disease, and high heart rate. More interventions were performed, hospital stays were longer, and the 28-day and in-hospital mortality rates were higher in the ICU group than in the ward group. Multivariate logistic regression analyses showed that risk factors affecting ICU admission were higher Sequential Organ Failure Assessment (SOFA) score, National Early Warning Score (NEWS), platelet count, and lactate level. ICU transfer was not associated with in-hospital mortality. CONCLUSIONS: Among RRT-screened patients, those with higher SOFA score, NEWS, and lactate level were more likely to be transferred to the ICU. Therefore, these patients should be closely monitored and considered for ICU transfer.

Usefulness of presepsin in predicting the prognosis of patients with sepsis or septic shock: a retrospective cohort study.

BACKGRUOUND: The diagnosis and prediction of prognosis are important in patients with sepsis, and presepsin is helpful. In this study, we aimed to examine the usefulness of presepsin in predicting the prognosis of sepsis in Korea. METHODS: Patients diagnosed with sepsis according to the sepsis-3 criteria were recruited into the study and classified into surviving and non-surviving groups based on in-hospital mortality. A total of 153 patients (33 and 121 patients with sepsis and septic shock, respectively) were included from July 2019 to August 2020. RESULTS: Among the 153 patients with sepsis, 91 and 62 were in the survivor and non-survivor groups, respectively. Presepsin (p=0.004) and lactate (p=0.003) levels and the sequential organ failure assessment (SOFA) score (p<0.001) were higher in the non-survivor group. Receiver operating characteristic curve analysis revealed poor performances of presepsin and lactate in predicting the prognosis of sepsis (presepsin: area under the curve [AUC]=0.656, p=0.001; lactate: AUC=0.646, p=0.003). The SOFA score showed the best performance, with the highest AUC value (AUC=0.751, p<0.001). The prognostic cutoff point for presepsin was 1,176 pg/mL. Presepsin levels higher than 1,176 pg/mL (odds ratio [OR], 3.352; p<0.001), higher lactate levels (OR, 1.203; p=0.003), and higher SOFA score (OR, 1.249; p<0.001) were risk factors for in-hospital mortality. CONCLUSION: Presepsin levels were higher in non-survivors than in survivors. Thus, presepsin may be a valuable biomarker in predicting the prognosis of sepsis.

Severe mediastinitis and pericarditis after endobronchial ultrasound-guided transbronchial needle aspiration: A case report.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and minimally invasive diagnostic tool for mediastinal and hilum evaluation. However, infectious complications may occur after EBUS-TBNA. Among these, mediastinitis and pericarditis are rare. CASE SUMMARY: A 67-year-old woman was referred to our hospital due to paratracheal lymph node enlargement on chest computed tomography (CT). EBUS-TBNA was performed on the lymph node lesions, and prophylactic oral antibiotics were administered. Seven days after EBUS-TBNA, the patient visited the emergency room with a high fever and chest pain. Laboratory test results revealed leukocytosis with a left shift and elevated C-reactive protein level (25.7 mg/dL). Chest CT revealed the formation of a mediastinal abscess in the right paratracheal lymph node and pericardial and bilateral pleural effusions. The patient received intravenous antibiotic treatment, cardiac drainage through pericardiocentesis, and surgical management. The patient recovered favorably and was discharged 31 d after the operation. CONCLUSION: Mediastinitis and pericarditis after EBUS-TBNA are rare but should be considered even after the use of prophylactic antibiotics.

New modified version of the Risk Adjustment for Congenital Heart Surgery category and mortality in premature infants with critical congenital heart disease.

BACKGROUND: Despite advances in neonatal intensive care and surgical procedures, perinatal mortality rates for premature infants with congenital heart disease (CHD) remain relatively high. PURPOSE: We aimed to describe the outcomes of premature infants with critical CHD and identify the risk factors including the new modified version of the Risk Adjustment for Congenital Heart Surgery (M-RACHS) category associated with in-hospital mortality in a Korean tertiary center. METHODS: This was a retrospective cohort study of premature infants with critical CHD admitted to the neonatal intensive care unit from January 2005 to December 2016. RESULTS: A total of 78 premature infants were enrolled. The median gestational age (GA) at birth was 34.9 weeks (range, 26.7-36.9 weeks), and the median birth weight was 1.91 kg (range, 0.53-4.38 kg). Surgical or percutaneous intervention was performed in 68 patients with a median GA at birth of 34.7 weeks (range, 26.7-36.8 weeks) and a median birth weight of 1.92 kg (range, 0.53-4.38 kg). The in-hospital survival rate was 76.9% among all enrolled preterm infants and 86.8% among patients who received an intervention. Very low birth weight (VLBW), persistent pulmonary hypertension of the newborn (PPHN), bronchopulmonary dysplasia (BPD), and M-RACHS category 5 or higher (more complex CHD) were independently associated with in-hospital mortality. For the 68 premature infants undergoing cardiac interventions, independent risk factors for mortality were VLBW, BPD, and CHD complexity. Late preterm infant and age at intervention were not associated with patient survival. CONCLUSION: For premature infants with critical CHD, VLBW, PPHN, BPD, and M-RACHS category ≥5 were risk factors for mortality. A careful approach to surgical intervention and prenatal care should be taken according to CHD type and neonatal condition.

Factors associated with Advanced Bone Age in Overweight and Obese Children.

PURPOSE: Obese children may often present with advanced bone age. We aimed to evaluate the correlation between factors associated with childhood obesity and advanced bone age. METHODS: We enrolled 232 overweight or obese children. Anthropometric and laboratory data, and the degree of nonalcoholic fatty liver disease (NAFLD) were measured. We analyzed factors associated with advanced bone age by measuring the differences between bone and chronological ages. RESULTS: The normal and advanced bone age groups were comprised of 183 (78.9%) and 49 (21.1%) children, respectively. The prevalence of advanced bone age significantly increased as the percentiles of height, weight, waist circumference, and body mass index (BMI) increased. BMI z-score was higher in the advanced bone age group than in the normal bone age group (2.43±0.52 vs. 2.10±0.46; p<0.001). The levels of insulin (27.80±26.13 µU/mL vs. 18.65±12.33 µU/mL; p=0.034) and homeostatic model assessment-insulin resistance (6.56±6.18 vs. 4.43±2.93; p=0.037) were significantly higher, while high density lipoprotein-cholesterol levels were lower (43.88±9.98 mg/dL vs. 48.95±10.50 mg/dL; p=0.005) in the advanced bone age group compared to those in the normal bone age group, respectively. The prevalence of advanced bone age was higher in obese children with metabolic syndrome than in those without (28.2% vs. 14.7%; p=0.016). The prevalence of advanced bone age was higher in obese children with a more severe degree of NAFLD. CONCLUSION: Advanced bone age is associated with a severe degree of obesity and its complications.

Group B streptococcal transmission via a prolonged colonizer in a neonatal intensive care unit.

This article reports five invasive Group B streptococcal (GBS) infections that occurred in a neonatal intensive care unit for about 3 months. This outbreak might have been associated with a prolonged GBS colonized infant and adjacent environmental contaminations. Infection control interventions prevented the additional spread of GBS infections.

Serum procalcitonin as an independent diagnostic markers of bacteremia in febrile patients with hematologic malignancies.

BACKGROUND: Serum procalcitonin (PCT) and C-reactive protein (CRP) are biomarkers of infection. In patients with hematologic disorders with or without hematopoietic stem cell transplantation (HSCT), it is difficult to distinguish bloodstream infections from aseptic causes of febrile episodes. The objective of this study was to investigate diagnostic values of PCT and CRP in predicting systemic bacterial infection in patients with hematologic malignancies. METHODS: Clinical and laboratory data of 614 febrile episode cases from 511 patients were analyzed. Febrile episodes were classified into four groups: (1) culture-positive bacterial infection by Gram-positive cocci (GPC), (2) culture-positive bacterial infection by Gram-negative bacilli (GNB), (3) fungal infection, and (4) viral infection or a noninfectious etiology. RESULTS: Of 614 febrile cases, systemic bacterial infections were confirmed in 99 (16.1%) febrile episodes, including 38 (6.2%) GPC and 61 (9.9%) GNB infections. PCT levels were significantly higher in GNB infectious episodes than those in febrile episodes caused by fungal infection (0.58 ng/mL (95% CI: 0.26-1.61) vs. 0.22 ng/mL (0.16-0.38), P = 0.047). Bacterial infectious episodes showed higher PCT and CRP levels than non-bacterial events (PCT: 0.49 (0.26-0.93) ng/mL vs. 0.20 (0.18-0.22) ng/mL, P < 0.001; CRP: 76.6 (50.5-92.8) mg/L vs. 58.0 (51.1-66.5) mg/L, P = 0.036). For non-neutropenic febrile episodes, both PCT and CRP discriminated bacteremia from non-bacteremia. However, in neutropenic febrile episodes, PCT only distinguished bacteremia from non-bacteremia. In non-neutropenic episode, both PCT and CRP showed good diagnostic accuracy (AUC: 0.757 vs. 0.763). In febrile neutropenia, only PCT discriminated bacteremia from non-bacterial infection (AUC: 0.624) whereas CRP could not detect bacteremia (AUC: 0.500, 95% CI: 0.439-0.561, P > 0.05). CONCLUSIONS: In this single-center observational study, PCT was more valuable than CRP for discriminating between bacteremia and non-bacteremia independent of neutropenia or HSCT.

Is the Diagnostic Trial with Proton Pump Inhibitors Reasonable for School Age Children with Gastroesophageal Reflux Symptoms?

PURPOSE: On the basis of evidence, we aimed to reevaluate the necessity of the empirical proton pump inhibitor (PPI) trial for children with suspected gastroesophageal reflux disease (GERD). METHODS: We analyzed the frequency of GERD in 85 school-age children with gastroesophageal reflux (GER) symptoms, who received 24-hour esophageal pH monitoring and/or upper endoscopy. According to the reflux index (RI), the children were classified into normal (RI <5%), intermediate (5%≤ RI <10%), or abnormal (RI ≥10%) groups. RESULTS: Fifty six were female and 29 were male. Their mean age was 12.6±0.5 (±standard deviation) years (range: 6.8-18.6). The RI analysis showed that the normal group included 76 patients (89.4%), the intermediate group included 6 patients (7.1%), and the abnormal group included 3 patients (3.5%). The DeMeester score was 5.93±4.65, 14.68±7.86 and 40.37±12.96 for the normal, intermediate and abnormal group, respectively (p=0.001). The longest reflux time was 5.56±6.00 minutes, 9.53±7.84 minutes, and 19.46±8.35 minutes in the normal, intermediate, and abnormal group, respectively (p=0.031). Endoscopic findings showed reflux esophagitis in 7 patients. On the basis of the Los Angeles Classification of Esophagitis, 5 of these patients were included in group A, 1 patient, in group B and 1 patient, in group C. CONCLUSION: The incidence of GERD was very low in school-age children with GER symptoms. Therefore, injudicious diagnostic PPI trials would be postponed until the actual prevalence of GERD is verified in future prospective studies.

Risk factors for persistent otitis media with effusion in children: a case-control study.

Background: Otitis media with effusion (OME) is defined as middle ear effusion without acute signs of infection. OME usually resolves spontaneously; however, persistent OME may require the insertion of a ventilation tube. This study investigated risk factors for persistent OME in children who undergo ventilation tube insertion. Methods: Children who were admitted to undergo ventilation tube insertion at Jeju National University Hospital between August 2015 and July 2016 were enrolled as the case group. Healthy children without persistent OME from August 2016 to July 2017 were enrolled as the control group. Baseline characteristics and predisposing factor data were collected using an interview questionnaire. Middle ear fluids were collected from the case group. Results: A total of 31 patients underwent ventilation tube insertion. The mean age of the case group was 4.53 years, with a male-to-female ratio of 21:10. Twenty-nine (93.5%) children attended a daycare center, and 21 (67.7%) had experience with bottle feeding. Fifteen (48.4%) children in the case group and 3 (9.7%) in the control group first attended a daycare center at <1 year of age (odds ratio=9.96; 95% confidence interval=2.44-39.70; p=0.001). No bacteria were found in middle ear fluid collected from the 31 operated children. Nasopharyngeal bacterial colonization was found in 13 (41.9%) and 17 (54.8%) children in the case and control groups, respectively. Conclusion: Earlier attendance at a daycare center was the only predisposing factor for ventilation tube insertion in our study. The aseptic nature of middle ear fluids found in children with OME highlights the efficacy of antimicrobial use.

Clinical Characteristics of Macrolide-Resistant Mycoplasma pneumoniae from Children in Jeju.

Mycoplasma pneumoniae is the major pathogen of community-acquired pneumonia in children. The prevalence of macrolide-resistant M. pneumoniae (MRMP) is important owing to the limited alternative therapies for children. We analyzed 111 M. pneumoniae obtained from 107 children admitted for lower respiratory tract infection at Jeju National University Hospital between 2010 and 2015. Macrolide resistance of M. pneumoniae was searched for using polymerase chain reaction (PCR) and sequencing. Of 107 clinical M. pneumoniae, 11 (10.3%) carried macrolide resistance mutations in the 23S rRNA gene. All macrolide resistance mutations were A2063G transitions. We found an acquired A2063G mutation of M. pneumoniae from a patient during macrolide treatment. Patients' characteristics and clinical severity did not differ between those with MRMP and macrolide-sensitive M. pneumoniae, with the exception of frequent pleural effusion in the MRMP group. The prevalence of MRMP (10.3%) in Jeju Island was relatively lower than those of surrounding countries in East Asia. Previous antimicrobial usage and timing of diagnostic test should be considered when determining of macrolide resistance of M. pneumoniae.

Risk factors for late-onset hyponatremia and its influence on neonatal outcomes in preterm infants.

Late-onset hyponatremia (LOH), hyponatremia occurring after two weeks of age with the achievement of full feeding, is the result of a negative sodium balance caused by inadequate salt intake or excessive salt loss due to immature renal or intestinal function in preterm infants. The aims of our study were to identify the risk factors for LOH and its influence on neonatal outcomes. This was a retrospective cohort analysis of 161 preterm infants born before 34 weeks of gestation between June 2009 and December 2010 at Seoul National University Hospital. LOH was defined as a sodium level ≤ 132 mEq/L or 133-135 mEq/L with oral sodium supplementation. LOH occurred in 49 (30.4%) of the studied infants. A lower gestational age, a shorter duration of parenteral nutrition, the presence of respiratory distress syndrome, the use of furosemide, and feeding with breast milk were significant risk factors for LOH. In terms of neonatal outcomes, the infants with LOH had longer hospital stays and higher risks of bronchopulmonary dysplasia and retinopathy of prematurity requiring surgery. LOH lasting at least 7 days significantly increased moderate to severe bronchopulmonary dysplasia, periventricular leukomalacia, and extra-uterine growth retardation. LOH is commonly observed in preterm infants; it may be a risk factor for bronchopulmonary dysplasia and retinopathy of prematurity or a marker of illness severity.

Avulsion fracture of the supinator crest of the proximal ulna in the context of elbow joint injuries.

PURPOSE: While performing CT examinations of the elbow, we frequently observed a previously undescribed fracture fragment of the supinator crest of the ulna. According to the anatomy of the lateral collateral ligament complex, this fracture might be an avulsion fracture of the annular ligament and/or the lateral ulnar collateral ligament. The aim of this study was to further characterize these fragments and document their associated injuries. METHODS: Retrospective evaluation of CT scans of the elbow was performed. Conventional X-ray and CT diagnoses were used to systematically document any associated injuries. RESULTS: A total of 152 CT scans were evaluated. The fragment in question was discovered in 17 patients (11.2%). The average age of the patients was 40 years (±14.9; 9-71 years). The fragment size varied between a few millimetres and 2.4 cm. Multifragmented fractures were observed. In 82.3% of the cases, associated radial head fractures were diagnosed. In 29.4%, a coronoid process fracture was present. Distal humerus fractures were found in 23.5%. Instability in the medial collateral ligament and an Osborne-Cotterill lesion were found in 11.8% of the patients, respectively. CONCLUSIONS: In a significant percentage of the population, a previously undescribed fracture fragment of the supinator crest of the ulna could be detected. The most frequently occurring associated injuries were fractures of the radial head, the coronoid process, and the distal humerus. The aetiology of these lesions is unknown; however, bony avulsion of the annular or the lateral ulnar collateral ligament seems to be the most likely cause. If this fragment is to be diagnosed by CT, the possibility of lateral or posterolateral instability should be considered.

A case of mucolipidosis II presenting with prenatal skeletal dysplasia and severe secondary hyperparathyroidism at birth.

Mucolipidosis II (ML II) or inclusion cell disease (I-cell disease) is a rarely occurring autosomal recessive lysosomal enzyme-targeting disease. This disease is usually found to occur in individuals aged between 6 and 12 months, with a clinical phenotype resembling that of Hurler syndrome and radiological findings resembling those of dysostosis multiplex. However, we encountered a rare case of an infant with ML II who presented with prenatal skeletal dysplasia and typical clinical features of severe secondary hyperparathyroidism at birth. A female infant was born at 37(+1) weeks of gestation with a birth weight of 1,690 g (<3rd percentile). Prenatal ultrasonographic findings revealed intrauterine growth retardation and skeletal dysplasia. At birth, the patient had characteristic features of ML II, and skeletal radiographs revealed dysostosis multiplex, similar to rickets. In addition, the patient had high levels of alkaline phosphatase and parathyroid hormone, consistent with severe secondary neonatal hyperparathyroidism. The activities of ß-D-hexosaminidase and α-N-acetylglucosaminidase were moderately decreased in the leukocytes but were 5- to 10-fold higher in the plasma. Examination of a placental biopsy specimen showed foamy vacuolar changes in trophoblasts and syncytiotrophoblasts. The diagnosis of ML II was confirmed via GNPTAB genetic testing, which revealed compound heterozygosity of c.3091C>T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation. The infant was treated with vitamin D supplements but expired because of asphyxia at the age of 2 months.

Detection of anti-aquaporin-4 antibodies in neuromyelitis optica: comparison of tissue-based and cell-based indirect immunofluorescence assays and ELISA.

NMO-IgG against aquaporin-4 (AQP4) is a specific marker for neuromyelitis optica (NMO). We evaluated the performance of different NMO-IgG detecting methods. In 124 sera (from 54 with NMO spectrum disorders including nine with NMO, ten with multiple sclerosis including two with OSMS, and 60 with other neurological diseases), NMO-IgG was measured with tissue-based indirect immunofluorescence (IIF-tissue) using mouse cerebellum, cell-based IIF (IIF-AQP4) using transfected HEK293 cells which express human AQP4, and AQP4 autoantibody detecting enzyme linked immunosorbent assay (ELISA-AQP4). The sensitivities and specificities of three assays were 44.4-55.6% and 87.0-92.2% for detecting NMO, and 11.1-20.4% and 95.7-97.1% for detecting NMO spectrum disorders. Although there was no significant difference, the patients with NMO or NMO spectrum disorders showed higher rates of seropositivity in the ELISA-AQP4 vs. IIF assays. Out of the 19 sera with NMO-IgG, in at least one test, only six (31.6%) were found to be positive by all three assays. Among the three methods, the ranges of co-negativities, co-positivities, and agreement were 77.4-97.4%, 42.9-75.0%, and 91.1-95.2% (kappa 0.475-0.641), respectively. In patients who had positive ELISA-AQP4 results, IIF-AQP4 positivity was associated with NMO (P = 0.01). In summary, we observed an increased prevalence of NMO-IgG in patients with NMO and NMO spectrum disorders. ELISA-AQP4 may be more sensitive and specific when confirmed by IIF-AQP4.

Application of calculated panel reactive antibody using HLA frequencies in Koreans.

BACKGROUND: Introduction of the Luminex panel reactive antibody (PRA)-single antigen (SA) assay has increased the detection rates of unacceptable antigens in sensitized patients; the calculated PRA (CPRA) level represents the percentage of actual organ donors that express 1 or more of these unacceptable antigens. We developed a CPRA calculator based on the HLA frequencies in Koreans to measure sensitization levels in Korean patients. METHODS: To develop the calculator, we obtained the HLA-A, HLA-B, and HLA-DR phenotypes of 1,622 Koreans, and compared these with previously reported frequencies in Koreans. Sera from patients awaiting kidney transplantation were tested for HLA antibodies by Luminex PRA-screen, PRA-identification (ID), and PRA-SA assays. The measured %PRA from the PRA-screen (N=55) and PRA-ID (N=71) were compared to the %CPRA for the unacceptable antigens obtained from PRA-SA. RESULTS: Phenotype frequencies used for the CPRA calculator agreed with previously reported data. The concordance rates among the 3 PRA methods for the detection of class I and class II antibodies were 76.1-81.8% (kappa, 0.519-0.636) and 72.7-83.6% (0.463-0.650), respectively. For the detection of broadly sensitized sera (>50% or >80%), the concordance rates were over 80%. In sera with 80-100% CPRA, 91.7% and 94.4% of the samples had concordant results (80-100% PRA) in the PRA-screen and PRA-ID assay, respectively. CONCLUSIONS: Although further clinical studies are required to confirm the benefits of CPRA values, adoption of CPRA analysis based on HLA frequencies in Koreans may be useful for sensitization measurements and organ-allocation algorithms.