Effect of donor-recipient size mismatch on long-term graft survival in pediatric kidney transplantation: a multicenter cohort study.

BACKGROUND: Donor-recipient size mismatching is commonly occurs in pediatric kidney transplantation (KT). However, its effect on graft survival remains unknown. This study aimed to determine the effect of donor-recipient size mismatch on the long-term survival rate of transplant kidneys in pediatric KT. METHODS: A total of 241 pediatric patients who received KT were enrolled. The medical records of all patients were retrospectively reviewed, and the correlation between donor-recipient size mismatch and graft function and long-term graft outcome was analyzed according to donor-recipient size mismatch. RESULTS: Recipients and donors' mean body weight at the time of KT were 34.31 ± 16.85 and 56.53 ± 16.73 kg, respectively. The mean follow-up duration was 96.49 ± 52.98 months. A significant positive correlation was observed between donor-recipient body weight ratio (DRBWR) or donor-recipient body surface area ratio (DRBSR) and graft function until 1 year after KT. However, this correlation could not be confirmed at the last follow-up. The results of long-term survival analysis using Fine and Gray's subdistribution hazard model showed no significant difference of the survival rate of the transplant kidney according to DRBWR or DRBSR. CONCLUSION: Donor-recipient size mismatch in pediatric KT is not an important factor in determining the long-term prognosis of transplant kidneys.

Long-term outcomes and associated prognostic risk factors of childhood-onset lupus nephritis.

Background: This study investigated the clinical characteristics and kidney outcomes of childhood-onset lupus nephritis (LN), and risk factors associated with prognosis. Methods: We enrolled 216 patients with histologically diagnosed LN during childhood. The Korean Society of Pediatric Nephrology organized a retrospective cohort study of childhood-onset LN in 13 major pediatric nephrology centers in South Korea. Results: The mean age at kidney biopsy was 13.2 ± 3.22 years. The main forms of presentation were nephrotic syndrome and/or hematuria in 152 patients (70.4%), and the most common histological finding was World Health Organization (WHO) class IV in 138 patients (63.9%), followed by WHO class III in 34 patients (15.7%). In the outcome analysis, the mean follow-up period of the patients was 7.8 ± 5.11 years. At last follow-up, 32 patients (14.8%) developed advanced chronic kidney disease (CKD). Male sex and failure to achieve remission at 12 months of treatment were significant risk factors for developing advanced CKD (hazard ratio of 2.57 and 2.29, respectively). Conclusion: Our study demonstrated the clinical characteristics and long-term outcomes of patients with childhood-onset LN. Male sex and failure to achieve remission in the first year of treatment were predictive of advanced CKD. Therefore, prompt awareness and close monitoring of these high-risk patients are needed, which may further improve the prognosis of children with LN.

De novo atypical hemolytic uremic syndrome associated with C3 gene mutation after kidney transplantation: a rare case of life-threatening diffuse alveolar hemorrhage in an adolescent.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) disease entity primarily attributed to genetic or acquired abnormalities in the alternative complement pathway. TMA can manifest in kidney transplant (KT) recipients owing to various factors, resulting in diverse clinical presentations. Given its adverse effects on allograft function and patient prognosis, genetic diagnostic approaches for aHUS are essential. Although rarely associated with diffuse alveolar hemorrhage, only a few mild cases have been reported to date. In this report, we present a case of the patient who experienced recurrent and life-threatening diffuse alveolar hemorrhage shortly after KT accompanied by graft failure. CASE PRESENTATION: An 18-year-old girl who underwent deceased donor KT developed recurrent diffuse alveolar hemorrhage with acute kidney injury, leading to graft failure. Microangiopathic hemolytic anemia, thrombocytopenia, and schistocytes in blood smears suggested the presence of TMA. The patient underwent therapeutic plasma exchange, and clinical condition improved during the procedure. Genetic testing confirmed a heterozygous c.1273C>T mutation in C3 gene, leading to the diagnosis of aHUS. However, after discontinuing the plasma exchange, the patient experienced seizures, recurrent pulmonary hemorrhage, and oliguria with recurring TMA features. The patient subsequently underwent eculizumab treatment, which resulted in complete remission, although hemodialysis was continued after graft nephrectomy. CONCLUSION: In patients presenting with unexplained pulmonary hemorrhage and kidney injury following KT, genetic aHUS should be considered as a potential differential diagnosis for TMA.

Association between serum total cholesterol and chronic kidney disease progression in children: results from the KNOW-PedCKD.

BACKGROUND: Dyslipidemia can cause cardiovascular disease and increase the fatality rate among children with chronic kidney disease (CKD); this makes early screening and treatment of dyslipidemia crucial. This study aimed to assess the association between the changes in serum total cholesterol levels over time and the degree of CKD progression in children. METHODS: From April 2011 to August 2021, 379 of the 432 participants enrolled in the KoreaN cohort study for Outcomes in patients With Pediatric CKD (KNOW-PedCKD) were included and divided into 4 categories based on total cholesterol levels (< 170 mg/dL, acceptable; 170-199, borderline; 200-239, high; and ≥ 240, very high). Survival analysis using conventional and time-dependent Cox proportional hazards model were performed for a composite event of CKD progression (≥ 50% decrease in estimated glomerular filtration rate from baseline, a twofold increase in creatinine, or the occurrence of dialysis or kidney transplantation). RESULT: The incidence of composite event of CKD progression was 96.3, 90.4, 87.3, and 270.6 cases per 1000 person-years in the acceptable, borderline, high, and very high categories, respectively. On using the time-dependent Cox proportional hazards model, the hazard ratio of the very high category was significantly higher than that of the acceptable category by 3.13 times as per univariate analysis and 2.37 times as per multivariate analysis. CONCLUSIONS: Very high serum total cholesterol is a significant risk factor for CKD progression in children. Lowering total cholesterol levels below the very high category in children with CKD may delay the progression of CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Genotype-phenotype correlation of X-linked Alport syndrome observed in both genders: a multicenter study in South Korea.

The genotype-phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype-phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25.0 years, and kidney survival showed significant differences between the non-truncating and truncating groups (P < 0.001, hazard ratio (HR) 2.8) and splicing and truncating groups (P = 0.002, HR 3.1). Sensorineural hearing loss was detected in 65.1% of male patients, while hearing survival periods showed a highly significant difference between the non-truncating and truncating groups (P < 0.001, HR 5.1). In female patients, approximately 20% developed kidney failure at the median age of 50.2 years. The kidney survival was significantly different between the non-truncating and truncating groups (P = 0.006, HR 5.7). Our findings support the presence of genotype-phenotype correlation not only in male patients but also in female patients with XLAS.

Levosimendan inhibits disulfide tau oligomerization and ameliorates tau pathology in TauP301L-BiFC mice.

Tau oligomers play critical roles in tau pathology and are responsible for neuronal cell death and transmitting the disease in the brain. Accordingly, preventing tau oligomerization has become an important therapeutic strategy to treat tauopathies, including Alzheimer's disease. However, progress has been slow because detecting tau oligomers in the cellular context is difficult. Working toward tau-targeted drug discovery, our group has developed a tau-BiFC platform to monitor and quantify tau oligomerization. By using the tau-BiFC platform, we screened libraries with FDA-approved and passed phase I drugs and identified levosimendan as a potent anti-tau agent that inhibits tau oligomerization. 14C-isotope labeling of levosimendan revealed that levosimendan covalently bound to tau cysteines, directly inhibiting disulfide-linked tau oligomerization. In addition, levosimendan disassembles tau oligomers into monomers, rescuing neurons from aggregation states. In comparison, the well-known anti-tau agents methylene blue and LMTM failed to protect neurons from tau-mediated toxicity, generating high-molecular-weight tau oligomers. Levosimendan displayed robust potency against tau oligomerization and rescued cognitive declines induced by tauopathy in the TauP301L-BiFC mouse model. Our data present the potential of levosimendan as a disease-modifying drug for tauopathies.

Characteristics of pediatric rhabdomyolysis and the associated risk factors for acute kidney injury: a retrospective multicenter study in Korea.

BACKGROUND: The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. METHODS: This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. RESULTS: Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53.6%) and infection (39.0%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. CONCLUSIONS: Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

Neonatal Lupus Erythematosus as a Rare Cause of Fever in Young Infants.

Neonatal lupus erythematosus (NLE) is a rare disease caused by passively transmitted autoantibodies from the mother. NLE is a multi-organ system disease characterized by cutaneous, cardiac, hematological, hepatobiliary, and neurological manifestations. This study aimed to review the various symptoms and clinical manifestations in young infants with NLE and their mothers. We conducted a retrospective review of medical records of patients with NLE who were both examined and treated at Pusan National University Children's Hospital between January 2009 and December 2020 and their mothers. Twenty-seven patients with NLE comprising 13 male patients (48.1%) and 14 female patients (51.9%) were included. The most common symptom was rash (40.7%), followed by fever (25.9%), arrhythmia (14.8%), splenomegaly (11.1%), and intrauterine growth retardation (7.4%). Seven patients with fever had various organ system manifestations, including cutaneous (100%), hematological (71.4%), hepatobiliary (57.1%), and central nervous system (CNS; 28.6%) manifestations. Two of the febrile patients had aseptic meningitis. Cutaneous, cardiac, hematological, hepatobiliary, and CNS involvement were noted in 44.4%, 18.5%, 51.9%, 40.7%, and 22.2% of the patients, respectively. Systemic lupus erythematosus (SLE) was the most common maternal disease (14/27, 51.9%). Ten mothers (37.0%) had not been diagnosed with any autoimmune disease until their babies were diagnosed. Among them, three were subsequently diagnosed with SLE, five were diagnosed with the Sjögren's syndrome, and two of them still had no known diagnosis of any autoimmune disorder. Fever is a common symptom of NLE; thus, when there is no clear focus of fever in infants, NLE needs to be considered, especially in cases with skin rashes.

Non-carbapenem antimicrobial therapy in young infant with urinary tract infections caused by community-acquired extended-spectrum ß-lactamase-producing Escherichia coli.

BACKGROUND: The frequency of urinary tract infections (UTIs) caused by community-acquired extended-spectrum ß-lactamase (CA-ESBL)-producing Enterobacteriaceae is increasing worldwide. Increased carbapenem use may lead to selection of carbapenem-resistant organisms, resulting in dire consequences for hospitals. We compared the outcomes of non-carbapenem antimicrobial therapy on UTIs caused by CA-ESBL-producing and non-producing Escherichia coli (E. coli) in infants younger than 6 months of age. METHODS: We conducted a retrospective chart review, from January 2010 to December 2018, in infants (0-6 months old) with diagnosed UTIs caused by CA-ESBL-producing and non-producing E. coli at the Pusan National University Children's Hospital. Chart reviews were completed for patients whose urine sample had been collected using urinary catheterization. We treated all patients using non-carbapenem antimicrobials. Two weeks after therapy completion, clinical states were evaluated. RESULTS: There were 105 and 582 patients diagnosed with UTIs caused by CA-ESBL-producing and non-producing E. coli, respectively. The mean age at diagnosis in ESBL and non-ESBL groups was 2.7 ± 1.6 and 2.8 ± 1.1 months (P = 0.711), respectively. There were no significant differences between ESBL and non-ESBL groups in the duration of fever (1.2 ± 0.5 and 1.2 ± 0.4 days, respectively, P = 0.761) or clinical cure states post therapy (101/105 and 567/582, respectively, P = 0.513). CONCLUSION: This study found no significant differences in treatment outcomes between ESBL and non-ESBL groups treated with non-carbapenem antimicrobials. Therefore, initially administered non-carbapenem antimicrobials can be continued in patients with UTIs caused by CA-ESBL-producing E. coli who show clinical improvement.

Recipient efficacy and safety of kidney transplantation from older living donor: consideration for using older kidney as a solution to the shortage of organs.

Background: As a solution to organ shortages, studies on kidney transplantation (KT) from older donors are being conducted. However, many controversies remain about its safety and efficacy. Methods: In Samsung Medical Center, from January 2000 to May 2015, 1,141 patients underwent living KT. Cases of retransplantation, recipient and donor aged younger than 18 years, and multiorgan transplantation were excluded, and a total of 859 cases were selected. Analysis was performed by dividing the patents into two groups a younger donor group (donors <60 years old; n=826) and an older donor group (donors ≥60 years old; n=33). Results: There were no significant differences between the two groups in patient death (log-rank P=0.173) or in postoperative complications. The older donor group had a higher acute rejection (P=0.034; hazard ratio [HR], 1.704) and graft failure rate (P=0.029, HR=2.352). There was no significant difference in the trend of estimated glomerular filtration rate over time (P=0.189). Conclusions: KT using kidneys from old-aged donors is safe, but there is room for improvement due to problems with higher acute rejection and graft failure rate.

Ampicillin-sulbactam monotherapy in infants with febrile urinary tract infections.

BACKGROUND: Cephalosporin is the most commonly used empirical agent for urinary tract infections (UTIs) in children. However, increasing use of cephalosporins can lead to an increase in resistant pathogens. This study therefore aims to investigate the effects of monotherapy with ampicillin-sulbactam as an alternative to cephalosporins. METHODS: All 2- to 24-month-old patients who were hospitalized at Pusan National University Children's Hospital due to a first episode of a febrile UTI during the 2-year period from 2012 to 2014 were included in the study. The subjects were divided into two groups according to their empirical therapy (cefotaxime or ampicillin-sulbactam). We determined the patients' UTI pathogens and their antibiotic susceptibilities and compared the effectiveness and the occurrence of adverse effects of ampicillin-sulbactam and cephalosporin therapy. RESULTS: Forty-six patients were treated with cefotaxime (group A) and 41 patients with ampicillin-sulbactam as the empirical antibiotic (group B). The most common pathogen in both groups was Escherichia coli, and antibiotic susceptibilities of the bacterial strains isolated from both groups were similar in ampicillin-sulbactam and cefotaxime. In addition, there was no significant difference in the duration of fever after treatment between the two groups (group A: 2.0 versus group B: 3.0, P = 0.331). There were no treatment failures and no recurrence in either group, even in patients with resistant pathogens. The most common side effect of the antibiotic agents was diarrhea. CONCLUSIONS: Ampicillin-sulbactam could be an effective alternative to cephalosporin as empiric antibiotic for the treatment of first-episode UTI in patients under 24 months of age.

The First Case of an Infant with Familial A20 Haploinsufficiency in Korea.

Haploinsufficiency of A20 (HA20) is a newly described autoinflammatory disease caused by loss-of-function mutations in the TNFAIP3 gene. Clinical phenotypes are heterogenous and resemble Behçet's disease, juvenile idiopathic arthritis, inflammatory bowel disease, or periodic fever syndrome, with symptoms developing at an early age. Here, we report the first case of infantile familial HA20 in Korea, which mimics neonatal lupus erythematosus (NLE). A 2-month-old infant exhibited symptoms including recurrent fever, erythematous rashes, and oral ulcers, with elevated liver enzymes, and tested positive for several autoantibodies, similar to systemic lupus erythematosus (SLE); therefore, she was suspected to have NLE. However, six months after birth, symptoms and autoantibodies persisted. Then, we considered the possibility of other diseases that could cause early onset rashes and abnormal autoantibodies, including autoinflammatory syndrome, monogenic SLE, or complement deficiency, all of which are rare. The detailed family history revealed that her father had recurrent symptoms, including oral and genital ulcers, knee arthralgia, abdominal pain, and diarrhea. These Behcet-like symptoms last for many years since he was a teenager, and he takes medications irregularly only when those are severe, but doesn't want the full-scale treatment. Whole-exome sequencing was conducted to identify a possible genetic disorder, which manifested as pathogenic variant nonsense mutation in the TNFAIP3 gene, leading to HA20. In conclusion, HA20 should be considered in the differential diagnosis of an infant with an early-onset dominantly inherited inflammatory disease that presents with recurrent oral and genital ulcerations and fluctuating autoantibodies. Additionally, it also should be considered in an infant with suspected NLE, whose symptoms and abnormal autoantibodies persist.

Visualization of soluble tau oligomers in TauP301L-BiFC transgenic mice demonstrates the progression of tauopathy.

Accumulation of abnormal tau aggregates in the brain is a pathological hallmark of multiple neurodegenerative disorders including Alzheimer's disease. Increasing evidence suggests that soluble tau aggregates play a key role in tau pathology as neurotoxic species causing neuronal cell death and act as prion-like seeds mediating tau propagation. Despite the pathological relevance, there is a paucity of methods to monitor tau oligomerization in the brain. As a tool to monitor tau self-assembly in the brain, we generated a novel tau transgenic mouse, named TauP301L-BiFC. By introducing bimolecular fluorescence complementation technique to human tau containing a P301L mutation, we were able to monitor and quantify tau self-assembly, represented by BiFC fluorescence in the brains of transgenic TauP301L-BiFC mice. TauP301L-BiFC mice showed soluble tau oligomerization from 3 months, showing significantly enriched BiFC fluorescence in the brain. Then, massive tau fragmentation occured at 6 months showing dramatically decreased TauP301L-BiFC fluorescence. The fragmented tau species served as a seed for insoluble tau aggregation. In a result, insoluble TauP301L-BiFC aggregates coaggregated with endogenous mouse tau accumulated in the brain, showing subsequently increased BiFC fluorescence from 9 months. Neuronal degeneration and cognitive deficits were observed from 12 months of age. TauP301L-BiFC mouse model demonstrated that methylene blue reduced the amount of soluble tau oligomers in the brain, resulting in the prevention of cognitive impairments. We assure that TauP301L-BiFC mice are a bona-fide animal tool to monitor pathological tau oligomerization in AD and other tauopathies.

Development of an Aryloxazole Derivative as a Brain-Permeable Anti-Glioblastoma Agent.

Glioblastoma drug development has been difficult due to the extremely low blood brain barrier (BBB) penetration of conventional anti-cancer agents. P-glycoprotein, an efflux membrane transporter, is responsible for the poor brain uptake of small and hydrophobic drug substances. To develop brain-penetrable anti-tumor agents, we designed colchicine derivatives containing an aryloxazole moiety, which is known to inhibit P-glycoprotein. Among those tested, an aryloxazole derivative named KIST-G1 showed the strongest anti-glioblastoma cell proliferation activity (IC50 = 3.2 ± 0.8 nM). Compared to colchicine, KIST-G1 showed dramatically increased BBB-permeable properties presenting 51.7 ± 0.5 (10-6 cm/s) parallel artificial membrane permeability assay (PAMPA) permeability and 45.0 ± 6.0% of P-gp inhibition. Aid by the BBB-permeable properties, KIST-G1 (5 mg/kg) suppressed glioblastoma cell growth and migration almost completely in the brain of glioblastoma xenograft models by showing 98.2 ± 0.1% reduced tumor area compared with phosphate buffered saline (PBS)-injected control. In comparison, temozolomide, which is the most widely used drug for glioblastoma, showed only moderate effects. Our results demonstrate the effectiveness of an aryloxazole moiety in targeting brain tumors and suggest KIST-G1 as a potent anti-glioblastoma agent.

Feasibility study on evaluating uranium enrichment with the High Resolution Gamma-Ray Spectrometry and X-ray fluorescence.

The uranium enrichment of the environmental sample should be analyzed to verify the declared information for the nuclear safeguards. The High-Resolution Gamma Spectrometry (HRGS) and Monochromatic Micro X-ray Fluorescence (MMXRF) is able to analyze the sample with a short detection time and high reproducibility. These are the advantage to measure the samples for screening before laboratory analysis. This study concentrated on uranium enrichment evaluation with the gamma-ray emission counts of 235U isotope (@185.7 keV) detected with the HRGS and counts of total uranium elements detected by MMXRF. As a result, the measured data were calculated for the uranium enrichment in three different ways: (i) Activity of 235U with the HRGS and mass of total uranium with the MMXRF, (ii) counts 235U with the HRGS and counts of total uranium, and (iii) activity of 235U and 238U with the HRGS. Based on the comparison with the mass spectrometry, method (iii) is able to derive the uranium enrichment the most accurately. However, method (ii) provides enough information for the screening to sort the sample for which laboratory analysis is necessary, when the sample's equilibrium status is not guaranteed.

Cerebrospinal fluid non-pleocytosis in pediatric enteroviral meningitis: Large-scale review.

BACKGROUND: Lack of cerebrospinal fluid (CSF) pleocytosis has been reported in some children with enteroviral meningitis (EVM). The aim of this paper was to investigate the clinical spectrum and related factors in EVM with CSF non-pleocytosis. METHODS: The databases of children diagnosed with EVM on CSF polymerase chain reaction between 2011 and 2014 were retrospectively reviewed. CSF pleocytosis was defined at each age using the criteria. Clinical and laboratory variables were compared between patients with CSF pleocytosis and non-pleocytosis. RESULTS: Of the 802 children of EVM, 25.4% (204/802) had CSF non-pleocytosis. In particular, CSF non-pleocytosis was found in 63.3% of the neonates versus in 22.2% of the children aged ≥1 year old, indicating that the ratio of CSF non-pleocytosis had a negative correlation with age (P < 0.001). As the main symptoms, fever (91.8% vs 86.8%, P = 0.038), headache (80.3% vs 63.7%, P < 0.001), and vomiting (75.9% vs 61.8%, P < 0.001) were significantly more frequent in CSF pleocytosis than in CSF non-pleocytosis. Patients with CSF non-pleocytosis had much lower peripheral leukocytosis (10 656 ± 3,662 vs 12 403 ± 4,207/mm3 , P = 0.014) and C-reactive protein (0.7±0.8 vs 1.2±1.5 mg/dL, P < 0.001), and earlier lumbar puncture <24 h after onset (42.6% vs 21.4%, p<0.001). No significant difference during the summer and autumn months was seen between the two groups (76.9% vs 81.9%, P = 0.169). CONCLUSION: CSF non-pleocytosis in childhood EVM was frequently observed, especially in young infants, regardless of season. We propose that CSF PCR testing for enterovirus can be helpful to recognize EVM in children with CSF non-pleocytosis.

Anthropometry-based estimation of body heat capacity in individuals aged 7-69 years: the Size Korea Survey 2010.

Although our previously developed anthropometry-based calculation of heat capacity (HC) for adults appeared to be precise and valid, its use in children and adolescents may be associated with bias. This study investigated a large dataset from the Size Korea survey, a national anthropometric survey conducted in 2010, to revalidate our previous HC equation and to develop another one that is appropriate for children and adolescents. We enrolled 12,766 participants aged 7-69 years with body composition data measured by multi-frequency bioelectrical impedance analysis. Age was associated with HC in children aged 7-19 years (R2 = 0.58) but not in adults (R2 = 0.007). Linear regression was appropriate to describe the relationship between HC and body surface area (BSA) in adults, whereas the regression in children and adolescent was quadratic. The previously developed HC equation had high reliability (intra-class correlation coefficient = 0.995) and predictive power (accurate prediction rate = 86.1%) in the >20 age group. The model composed of sex, body weight, BSA, and BSA2 was appropriate for the prediction of HC in young individuals aged 7-19 years. In conclusion, anthropometric-based modelling is a simple, reliable, and useful method for the calculation of HC.

A rare case of multiple pituitary adenomas in an adolescent Cushing disease presenting as a vertebral compression fracture.

Cushing disease in children and adolescents, especially with multiple pituitary adenomas (MPAs), is very rare. We report 17-year-old boy with MPAs. He presented with a vertebral compression fracture, weight gain, short stature, headache, and hypertension. On magnetic resonance imaging (MRI), only a left pituitary microadenoma was found. After surgery, transient clinical improvement was observed but headache and hypertension were observed again after 3 months later. Follow-up MRI showed a newly developed right pituitary microadenoma 6 months after the surgery. The need for careful clinical and radiographic follow-up should be emphasized in the search for potential MPAs in patients with persistent Cushing disease.

Multiplex Polymerase Chain Reaction for Identification of Shigellae and Four Shigella Species Using Novel Genetic Markers Screened by Comparative Genomics.

In the detection of Shigella species using molecular biological methods, previously known genetic markers for Shigella species were not sufficient to discriminate between Shigella species and diarrheagenic Escherichia coli. The purposes of this study were to screen for genetic markers of the Shigella genus and four Shigella species through comparative genomics and develop a multiplex polymerase chain reaction (PCR) for the detection of shigellae and Shigella species. A total of seven genomic DNA sequences from Shigella species were subjected to comparative genomics for the screening of genetic markers of shigellae and each Shigella species. The primer sets were designed from the screened genetic markers and evaluated using PCR with genomic DNAs from Shigella and other bacterial strains in Enterobacteriaceae. A novel Shigella quintuplex PCR, designed for the detection of Shigella genus, S. dysenteriae, S. boydii, S. flexneri, and S. sonnei, was developed from the evaluated primer sets, and its performance was demonstrated with specifically amplified results from each Shigella species. This Shigella multiplex PCR is the first to be reported with novel genetic markers developed through comparative genomics and may be a useful tool for the accurate detection of the Shigella genus and species from closely related bacteria in clinical microbiology and food safety.