Treatment of Multidrug-resistant Pseudomonas aeruginosa Bacteremia in a Immunocompromised Child With Ceftolozane-tazobactam

With the widespread use of broad-spectrum antibiotics in clinical practice, the emergence of multidrug-resistant (MDR) gram-negative bacteria has become a global problem. The MDR Pseudomonas aeruginosa infection is especially difficult to treat and increases mortality in critically ill patients. Ceftolozane-tazobactam (Zerbaxa™) is a fifth-generation cephalosporin and beta-lactamase inhibitor that has proved to be effective for treating complicated urinary tract infections and complicated intra-abdominal infections caused by MDR P. aeruginosa. Herein, we report the first case of pediatric hematologic cancer in Korea that was successfully treated for MDR P. aeruginosa bacteremia with Ceftolozane-tazobactam.

Incidence and Mortality Trends in Critically Ill Children: A Korean Population-Based Study

Background@#Monitoring mortality trends can help design ways to improve survival, but observation of national mortality trends in critically ill children is lacking for the Korean population Methods: We analyzed the incidence and mortality trends of children younger than 18 years admitted to an intensive care unit (ICU) from 2012 to 2018 using the Korean National Health Insurance database. Neonates and neonatal ICU admissions were excluded. Multivariable logistic regression analyses were performed to estimate the odds ratio of in-hospital mortality according to admission year. Trends in incidence and in-hospital mortality of subgroups according to admission department, age, presence of intensivists, admissions to pediatric ICU, mechanical ventilation, and use of vasopressors were evaluated. @*Results@#The overall mortality of critically ill children was 4.4%. There was a significant decrease in mortality from 5.5% in 2012 to 4.1% in 2018 (Pfor trend < 0.001). The incidence of ICU admission in children remained around 8.5/10,000 population years (Pfor trend = 0.069). In-hospital mortality decreased by 9.2% yearly in adjusted analysis (P < 0.001). The presence of dedicated intensivists (Pfor trend < 0.001, mortality decrease from 5.7% to 4.0%) and admission to pediatric ICU (Pfor trend < 0.001, mortality decrease from 5.0% to 3.2%) were associated with significant decreasing trends in mortality. @*Conclusion@#Mortality among critically ill children improved during the study period, and the improving trend was prominent in children with high treatment requirements. Varying mortality trends, according to ICU organizations, highlight that advances in medical knowledge should be supported structurally.

Comparative Genomics Platform and Phylogenetic Analysis of Fungal Laccases and Multi-Copper Oxidases

Laccases (EC 1.10.3.2), a group of multi-copper oxidases (MCOs), play multiple biological functions and widely exist in many species. Fungal laccases have been extensively studied for their industrial applications, however, there was no database specially focused on fungal laccases. To provide a comparative genomics platform for fungal laccases, we have developed a comparative genomics platform for laccases and MCOs (http://laccase.riceblast.snu.ac.kr/). Based on protein domain profiles of characterized sequences, 3,571 laccases were predicted from 690 genomes including 253 fungi. The number of putative laccases and their properties exhibited dynamic distribution across the taxonomy. A total of 505 laccases from 68 genomes were selected and subjected to phylogenetic analysis. As a result, four clades comprised of nine subclades were phylogenetically grouped by their putative functions and analyzed at the sequence level. Our work would provide a workbench for putative laccases mainly focused on the fungal kingdom as well as a new perspective in the identification and classification of putative laccases and MCOs.

Genomic Insights into the Rice Blast Fungus through Estimation of Gene Emergence Time in Phylogenetic Context

The rice blast fungus, Magnaporthe oryzae, is an important pathogen of rice plants. It is well known that genes encoded in the genome have different evolutionary histories that are related to their functions. Phylostratigraphy is a method that correlates the evolutionary origin of genes with evolutionary transitions. Here we applied phylostratigraphy to partition total gene content of M. oryzae into distinct classes (phylostrata), which we designated PS1 to PS7, based on estimation of their emergence time. Genes in individual phylostrata did not show significant biases in their global distribution among seven chromosomes, but at the local level, clustering of genes belonging to the same phylostratum was observed. Our phylostrata-wide analysis of genes revealed that genes in the same phylostratum tend to be similar in many physical and functional characteristics such as gene length and structure, GC contents, codon adaptation index, and level of transcription, which correlates with biological functions in evolutionary context. We also found that a significant proportion of genes in the genome are orphans, for which no orthologs can be detected in the database. Among them, we narrowed down to seven orphan genes having transcriptional and translational evidences, and showed that one of them is implicated in asexual reproduction and virulence, suggesting ongoing evolution in this fungus through lineage-specific genes. Our results provide genomic basis for linking functions of pathogenicity factors and gene emergence time.

Early Infliximab Yields Superior Long-Term Effects on Linear Growth in Pediatric Crohn's Disease Patients

BACKGROUND/AIMS: Information regarding the efficacy of early infliximab treatment in pediatric patients with Crohn's disease (CD) is limited. We aimed to evaluate the impact of early combined immunosuppression on linear growth in pediatric patients with CD by performing step-up comparisons. METHODS: This retrospective study included pediatric patients with moderate-to-severe CD, who received a combination therapy with infliximab and azathioprine for at least 3 years and sustained corticosteroid-free remission without loss of response. The z-scores of the growth indicators obtained at the time of diagnosis and annually for 3 years thereafter were compared between the two groups. RESULTS: The early combined immunosuppression group displayed significantly increased linear growth 3 years after diagnosis (p=0.026). A significant difference was also observed in the linear growth 3 years after diagnosis between subgroups of Tanner stages 1–2 (p=0.016). CONCLUSIONS: The early introduction of biologics should be considered to improve linear growth in pediatric patients with CD.

Complicated Azygos Vein Aneurysm in an Infant Presenting with Acute Pulmonary Thromboembolism

Azygos vein aneurysm is a rare cause of mediastinal mass. Most cases present as an incidental finding on imaging modalities, but in few cases the thrombosis in the aneurysm leads to pulmonary thromboembolism, which may require surgical resection. We present a case where, for the first time, a case of a complicated azygos vein aneurysm was diagnosed in infancy, which required surgical resection.

In Silico Sequence Analysis Reveals New Characteristics of Fungal NADPH Oxidase Genes

NADPH oxidases (Noxes), transmembrane proteins found in most eukaryotic species, generate reactive oxygen species and are thereby involved in essential biological processes. However, the fact that genes encoding ferric reductases and ferric-chelate reductases share high sequence similarities and domains with Nox genes represents a challenge for bioinformatic approaches used to identify Nox-encoding genes. Further, most studies on fungal Nox genes have focused mainly on functionality, rather than sequence properties, and consequently clear differentiation among the various Nox isoforms has not been achieved. We conducted an extensive sequence analysis to identify putative Nox genes among 34 eukaryotes, including 28 fungal genomes and one Oomycota genome. Analyses were performed with respect to phylogeny, transmembrane helices, di-histidine distance and glycosylation. Our analyses indicate that the sequence properties of fungal Nox genes are different from those of human and plant Nox genes, thus providing novel insight that will enable more accurate identification and characterization of fungal Nox genes.

Eukaryotic DNAJ/K Database: A Comprehensive Phylogenomic Analysis Platform for the DNAJ/K Family

Proteins in DNAJ/K families are ubiquitous, from prokaryotes to eukaryotes, and function as molecular chaperones. For systematic phylogenomics of the DNAJ/K families, we developed the Eukaryotic DNAJ/K Database (EDD). A total of 12,908 DNAJs and 4,886 DNAKs were identified from 339 eukaryotic genomes in the EDD. Kingdom-wide comparison of DNAJ/K families provides new insights on the evolutionary relationship within these families. Empowered by 'class', 'cluster', and 'taxonomy' browsers and the 'favorite' function, the EDD provides a versatile platform for comparative genomic analyses of DNAJ/K families.

Laparoscopic Appendectomy is Feasible for Inexperienced Surgeons in the Early Days of Individual Laparoscopic Training Courses

PURPOSE: Recently, laparoscopic appendectomy (LA) has been widely performed in developed countries. In addition, minimally invasive surgery such as LA is a challenge to surgical residents. The aim of this study is to evaluate learning curve of residents in comparison to that of experienced surgeons. METHODS: Fifty cases of LA that were performed by experienced surgeons (group A) and forty-seven cases of LA that were performed by 8 residents (group B) were reviewed retrospectively. RESULTS: Operative time was longer in group B (50.8+/-12 vs. 82.8+/-40 min. P<0.001). Hospital days of group B was shorter (4.8+/-2.4 vs. 3.7+/-2.1 days P=0.021). No other parameters were statistically significant. In group A, wound infection developed in 1 case. In group B, wound infection developed in 4 cases, intraabdominal abscess in 1, subcutaneous emphysema in 1. CONCLUSION: Inexperienced surgeons can perform laparoscopic appendectomy easily in the early days of individual laparoscopic training course.

Concurrent Papillary and Medullary Carcinoma of the Thyroid Gland

We report here on a rare case of concurrent papillary thyroid carcinoma and medullary thyroid carcinoma on each of the lobes of the thyroid gland. A 43-year-old female presented with a one-week history of throat discomfort. A neck ultrasonogram (US) was done, along with fine needle aspiration biopsy (FNAB) of the left thyroid nodule, and the results showed papillary cancer. This patient underwent total thyroidectomy and central compartment neck dissection. The pathologic diagnosis of the nodule at the left lobe of the thyroid was papillary thyroid carcinoma (PTC) and the right thyroid nodule was medullary thyroid carcinoma (MTC).

A Clinical Review of Papillary Microcarcinoma of the Thyroid / 대한내분비외과학회지

PURPOSE: Most cases of papillary microcarcinomas of the thyroid (PMC) are not palpable and are clinically asymptomatic. The natural history of the microcarcinoma is unclear and remains debatable. There is continued discussion of whether thyroid microcarcinomas should be treated surgically and to what extent surgical removal should be extended. The main goal of this study was to analyze the clinical features and to determine the appropriate surgical treatment for well differentiated PMC in one lobe of the thyroid with favorable features in regard to consideration of radical surgery. METHODS: We studied 134 patients with the histological diagnosis of PMC from March 2003 to January 2006. The tumor was defined as 10 mm or less in the greatest diameter according to the World Health Organization guidelines. For all patients we confirmed the diagnosis by ultrasoundguided fine-needle aspiration biopsy (US-FNAB) preoperatively. There were 11 men and 123 women. The age at initial treatment ranged from 22 to 74 years (mean 46). Thyroid resection was lobectomy in 31 (23.1%) and total thyroidectomy (TT) in 103 (76.9%). CCND was performed routinely at the time of thyroidectomy. Lateral neck dissection was carried out in eight patients (5.9%) who had biopsy-proven metastatic cervical lymphadenopathy demonstrated clinically or by imaging. Patient records were reviewed retrospectively. Categorical variables were analyzed using the chi-square test or Fisher's exact test. Two-sided Student's t-test was used to compare paired data. RESULTS: The mean tumor size was 6.77 mm. PMC was associated in 36.6% (49/134) with lymph node metastasis, in 20.1% (27/134) with multifocality and in 26.9% (36/134) with capsular invasion. The mean tumor size differences influenced lymph node metastasis (LNM) (P5 mm) influenced multifocality (P=0.031). The frequency of LNM, in the contralateral central compartment of patients with lesions in one lobe of thyroid, without capsular invasion, underwent TT with CCND in 1.7% (1/59). CONCLUSION: Currently, thyroidectomy with lymph node dissection has been the recommended first line treatment for microcarcinoma of the thyroid because of the high incidence of multifocality and lymph node metastasis. However, when we excluded patients with aggressive prognostic features we could successfully perform lobectomy and isthmusectomy with ipsilateral CCND based on considerations of radical surgery (98.3%, 58/59). However, subsequent surgery for contralateral nodes or lobe metastasis would not be easy and a longer follow-up period would be required to confirm our hypothesis with regard to the long term recurrence and mortality.

The Influence of Low Calcium Concentration Hemodialysis on Cardiovascular Response / 대한신장학회잡지

OBJECTIVE: Arterial compliance (AC) reflects the buffering function of the vessel. Low AC caused by arterial stiffness increases pulse pressure amplitude. Therefore, Low AC must be correlated with high cardiovascular mobidity and mortality in HD patients. Dialysate calcium concentration is potentially a main determinant of serum ionized calcium level and the vasoconstriction is associated with high calcium concentration. Therefore, We conducted a study for evaluation of the interdialytic effects of treatment with a low dialysate calcium (LdCa) concentration and high dialysate calcium (HdCa) concentration on the changes of AC, BP, biochemical parameters. METHODS: Eight HD patient (mean age 45.5, sex ratio 1 : 1) were studied. The mean HD period was 3 years. Arterial Compliance, stroke Volume, SBP, DBP, PP, MAP, Ionized Ca, T-CO2, P and CaxP product were compared after treatment with a LdCa and HdCa concentration for each 10 sessions. RESULTS: AC were 0.143+/-0.076 mm2/kPa in baseline, 0.166+/-0.097 mm2/kPa in LdCa (1.25 mmol/L) dialysate, 0.142+/-0.082 mm2/kPa in HdCa (1.75 mmol/L) dialysate. SBP, DBP, MAP and PP were 157.75+/-15.97, 94.25+/-9.48, 114.12+/-10.56, 63.50+/-10.87 mmHg in baseline and 135.25+/-13.00, 78.75+/-11.24, 98.37+/-15.14, 56.50+/-5.95 mmHg in LdCa dialysate and 160.50+/-15.36, 94.05+/-10.34, 115.75+/-9.64, 62.00+/-15.71 mmHg in HdCa dialysate. Ionized Ca were 4.66+/-0.40 mg/dL in baseline, 4.45+/-0.28 mg/dL in LdCa dialysate and 4.65+/-0.43 mg/dL in HdCa dialysate. However, there were no changes of other biochemical parameters. CONCLUSION: Treatment with LdCa dialysis, by minimizing the risk for LdCa-induced hypocalcemia, may have a beneficial role in the prevention of the ongoing reduction of arterial compliance in HD patients and thus improve cardiovascular prognosis.