Comparison of Clinical Outcomes for Glycopeptides and Beta-Lactams in Methicillin-Susceptible Staphylococcus Aureus Bloodstream Infections

Purpose@#This study aimed to provide compelling evidence of anti-staphylococcal beta-lactam use for methicillin-susceptible Staphylococcus aureus bloodstream infection (MSSA BSI). @*Materials and Methods@#We retrospectively collected data on patients with MSSA BSI who were admitted to two academic tertiary-care hospitals from 2010 to 2018. Only patients who received nafcillin, cefazolin, vancomycin, or teicoplanin as definitive therapy were included. The primary outcome was 28-day mortality. To perform unbiased comparisons between both treatments, we used inverse probability of treatment weighting (IPTW) analysis. @*Results@#A total of 359 patients were divided into two groups based on the definitive therapy used: beta-lactams (n=203), including nafcillin or cefazolin; and glycopeptides (n=156), including vancomycin or teicoplanin. In the IPTW analysis, glycopeptides were associated with significantly increased odds of 28-day mortality (adjusted odds ratio, 3.37; 95% confidence interval, 1.71– 6.61; p<0.001). The rate of primary outcome in prespecified subgroups was largely consistent with the main analysis. @*Conclusion@#Definitive therapy with beta-lactams in patients with MSSA BSI was associated with lower 28-day mortality compared to definitive therapy with glycopeptides.

The Use of Anticholinergic Drugs in the Elderly

Anticholinergic drugs are commonly prescribed for treatment in specific clinical conditions in the elderly. Despite these thera-peutic benefits, the use of anticholinergic drugs is limited due to central or peripheral anticholinergic side effects. Especially in the elderly, since long-term use of anticholinergic drugs is related to mild cognitive impairment and dementia, it is necessary to pre-scribe anticholinergic drugs appropriately. In this review, we try to cover pathophysiology, prevalence of anticholinergic drugs, measuring tools of anticholinergic activity. Also, the negative effects on cognitive function, psychiatric symptoms, delirium, hospi-talization, functionality and mortality, and the benefits and limitations of discontinuing anticholinergic drugs are discussed. Finally, we suggest appropriate prescriptions of anticholinergic drugs for the elderly in various clinical conditions.

PIG3 Regulates p53 Stability by Suppressing Its MDM2-Mediated Ubiquitination

Under normal, non-stressed conditions, intracellular p53 is continually ubiquitinated by MDM2 and targeted for degradation. However, in response to severe genotoxic stress, p53 protein levels are markedly increased and apoptotic cell death is triggered. Inhibiting the ubiquitination of p53 under conditions where DNA damage has occurred is therefore crucial for preventing the development of cancer, because if cells with severely damaged genomes are not removed from the population, uncontrolled growth can result. However, questions remain about the cellular mechanisms underlying the regulation of p53 stability. In this study, we show that p53-inducible gene 3 (PIG3), which is a transcriptional target of p53, regulates p53 stability. Overexpression of PIG3 stabilized both endogenous and transfected wild-type p53, whereas a knockdown of PIG3 lead to a reduction in both endogenous and UV-induced p53 levels in p53-proficient human cancer cells. Using both in vivo and in vitro ubiquitination assays, we found that PIG3 suppressed both ubiquitination- and MDM2-dependent proteasomal degradation of p53. Notably, we demonstrate that PIG3 interacts directly with MDM2 and promoted MDM2 ubiquitination. Moreover, elimination of endogenous PIG3 in p53-proficient HCT116 cells decreased p53 phosphorylation in response to UV irradiation. These results suggest an important role for PIG3 in regulating intracellular p53 levels through the inhibition of p53 ubiquitination.

A Case of Congenital Lymphatic Dysplasia Complicated by Hydrops Fetalis

Congenital lymphatic dysplasia is a rare congenital maldevelopment of the lymphatic system, in which dysfunction of the lymphatic system may cause leakage of lymph fluid into the limbs and the pleural, pericardial, or peritoneal cavity. We experienced a case of hydrops fetalis with subcutaneous lymphedema, chylothorax, chylous ascites and pericardial effusion. Lymphangiography revealed a critical defect of lymphatic system. Here, we report the first case of premature infant with congenital lymphatic dysplasia confirmed by lymphangiography, which is the first reported in Korea.

RNA-Seq for Gene Expression Profiling of Human Necrotizing Enterocolitis: a Pilot Study

Necrotizing enterocolitis (NEC) characterized by inflammatory intestinal necrosis is a major cause of mortality and morbidity in newborns. Deep RNA sequencing (RNA-Seq) has recently emerged as a powerful technology enabling better quantification of gene expression than microarrays with a lower background signal. A total of 10 transcriptomes from 5 pairs of NEC lesions and adjacent normal tissues obtained from preterm infants with NEC were analyzed. As a result, a total of 65 genes (57 down-regulated and 8 up-regulated) revealed significantly different expression levels in the NEC lesion compared to the adjacent normal region, based on a significance at fold change ≥ 1.5 and P ≤ 0.05. The most significant gene, DPF3 (P < 0.001), has recently been reported to have differential expressions in colon segments. Our gene ontology analysis between NEC lesion and adjacent normal tissues showed that down-regulated genes were included in nervous system development with the most significance (P = 9.3 × 10⁻⁷; P(corr) = 0.0003). In further pathway analysis using Pathway Express based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, genes involved in thyroid cancer and axon guidance were predicted to be associated with different expression (P(corr) = 0.008 and 0.020, respectively). Although further replications using a larger sample size and functional evaluations are needed, our results suggest that altered gene expression and the genes' involved functional pathways and categories may provide insight into NEC development and aid in future research.

Efficacy of Ultrasound-guided Contrast Enema on Meconium Plug Syndrome in Preterm Infants / 대한주산의학회잡지

PURPOSE: This study aims to compare the effectiveness and safety of ultrasound-guided contrast enema comparing with exploratory laparotomy for meconium plug syndrome in preterm infants. METHODS: Fifty-three preterm infants who were diagnosed with meconium plug syndrome among the neonates admitted to the Neonatal Intensive Care Unit of the Seoul National University Bundang Hospital from March 2008 to August 2015 were analyzed retrospectively. Four-teen infants among the 53 infants were excluded and Thirty-nine infants were analyzed. That time were divided into Period I and Period II. There was no pediatric radiologist and we couldn't try contrast enema in Period I. Pediatric radiologist was appointed and ultrasound guided contrast enema has been available in Period II. RESULTS: There were no specific differences of demographic characters between both Periods. Invasive procedure including contrast enema was increased in Period II than Period I (81% vs. 42%; P<0.05) and there were more exploratory laparotomy in Period I than in Period II (42% vs. 7%; P<0.05). Complications after treatment of meconium plug syndrome were more frequent in exploratory laparotomy groups than in ultrasound-guided contrast enema (57% vs. 0%; P<0.05) and total parenteral nutrition days were longer in laparotomy groups than in contrast enema groups (61±30 days vs. 31±13 days; P<0.05). CONCLUSION: We suggest that ultrasound-guided contrast enema with hyperosmolar water-soluble contrast is more therapeutic and safe therapy than exploratory laparotomy for meconium plug syndrome.

Efficacy of Ultrasound-guided Contrast Enema on Meconium Plug Syndrome in Preterm Infants / 대한주산의학회잡지

PURPOSE: This study aims to compare the effectiveness and safety of ultrasound-guided contrast enema comparing with exploratory laparotomy for meconium plug syndrome in preterm infants. METHODS: Fifty-three preterm infants who were diagnosed with meconium plug syndrome among the neonates admitted to the Neonatal Intensive Care Unit of the Seoul National University Bundang Hospital from March 2008 to August 2015 were analyzed retrospectively. Four-teen infants among the 53 infants were excluded and Thirty-nine infants were analyzed. That time were divided into Period I and Period II. There was no pediatric radiologist and we couldn't try contrast enema in Period I. Pediatric radiologist was appointed and ultrasound guided contrast enema has been available in Period II. RESULTS: There were no specific differences of demographic characters between both Periods. Invasive procedure including contrast enema was increased in Period II than Period I (81% vs. 42%; P<0.05) and there were more exploratory laparotomy in Period I than in Period II (42% vs. 7%; P<0.05). Complications after treatment of meconium plug syndrome were more frequent in exploratory laparotomy groups than in ultrasound-guided contrast enema (57% vs. 0%; P<0.05) and total parenteral nutrition days were longer in laparotomy groups than in contrast enema groups (61±30 days vs. 31±13 days; P<0.05). CONCLUSION: We suggest that ultrasound-guided contrast enema with hyperosmolar water-soluble contrast is more therapeutic and safe therapy than exploratory laparotomy for meconium plug syndrome.

Ruptured Tricuspid Valve Papillary Muscle in a Neonate with Intractable Persistent Fetal Circulation

Unguarded tricuspid regurgitation (TR) due to a flail tricuspid leaflet is a rare condition of newborn cyanosis. A high perinatal mortality has been associated with this fatal condition. But, there are feasible surgical repairs to improve survival. We report the case of a male full-term neonate with intractable hypoxia. He had profound tricuspid insufficiency and leaflet prolapse caused by a ruptured papillary muscle supporting the anterior leaflet of the tricuspid valve. He presented with severe cyanosis and respiratory distress immediately after birth. Despite medical management, the pulmonary vascular resistance was not decreased and a low cardiac output persisted. Initial stabilization was accomplished with nitric oxide and extracorporeal membrane oxygenation. The tricuspid valve repair surgery was successfully performed subsequently. TR resulting from papillary muscle rupture is a potentially lethal condition. Timely diagnosis and proper surgical treatment can be lifesaving.

A Case of Congenital Hypothyroidism in a Preterm Infant Presenting with Meconium Obstruction

Many infants with congenital hypothyroidism have few or no clinical manifestations at birth. In preterm infants, discovering related signs and symptoms of congenital hypothyroidism is even more difficult, despite the higher incidence of transient thyroid function abnormalities. Therefore, these patients need to be closely monitored during the early neonatal period. We report a case of a very low birth weight infant presenting with meconium obstruction concurrent with congenital hypothyroidism in the early neonatal period. Unless diagnosed and treated appropriately, meconium obstruction of prematurity may lead to feeding intolerance, intestinal perforation, necrotizing enterocolitis, and sepsis. It is important for medical caregivers to understand that meconium obstruction can be an early sign of congenital hypothyroidism in preterm infants with abdominal distension.

Identification of a novel mutation in a patient with pseudohypoparathyroidism type Ia / 소아과

Pseudohypoparathyroidism type Ia (PHP Ia) is a disorder characterized by multiform hormonal resistance including parathyroid hormone (PTH) resistance and Albright hereditary osteodystrophy (AHO). It is caused by heterozygous inactivating mutations within the Gs alpha-encoding GNAS exons. A 9-year-old boy presented with clinical and laboratory abnormalities including hypocalcemia, hyperphosphatemia, PTH resistance, multihormone resistance and AHO (round face, short stature, obesity, brachydactyly and osteoma cutis) which were typical of PHP Ia. He had a history of repeated convulsive episodes that started from the age of 2 months. A cranial computed tomography scan showed bilateral calcifications in the basal ganglia and his intelligence quotient testing indicated mild mental retardation. Family history revealed that the patient's maternal relatives, including his grandmother and 2 of his mother's siblings, had features suggestive of AHO. Sequencing of the GNAS gene of the patient identified a heterozygous nonsense mutation within exon 11 (c.637 C>T). The C>T transversion results in an amino acid substitution from Gln to stop codon at codon 213 (p.Gln213*). To our knowledge, this is a novel mutation in GNAS.

Timing of Liberation from Ventilation Assistance and Decannulation in Preterm Infants with Bronchopulmonary Dysplasia after Tracheostomy

PURPOSE: We aimed to evaluate the clinical outcomes of preterm infants with bronchopulmonary dysplasia after tracheostomy. METHODS: We retrospectively examined 24 preterm infants with bronchopulmonary dysplasia who were admitted to the neonatal intensive care unit of Seoul National University Hospital and treated with tracheostomy between January 1999 and December 2013. We collected data on the age at tracheostomy, indication for the tracheostomy, and the long-term outcomes. RESULTS: Of the admitted patients, 1.0% were treated with tracheostomy, and the median age at tracheostomy was 185 days. Fifteen patients (62.5%) were weaned from mechanical ventilation. Of these, 56.5% patients were weaned from positive pressure ventilation (PPV) within 24 months, and 81.3% were weaned from PPV within 60 months. The median time from the tracheostomy procedure to independent PPV was 15.9 months. Decannulation was achieved in 8 patients (33.3%); of these, 41.5% were decannulated within 24 months, and 69.9% were decannulated within 60 months. The median time from the tracheostomy procedure to decannulation was 48.8 months. In patients without airway disease, the time from the tracheostomy procedure to independent PPV and decannulation was 15.6 months. In patients with airway disease, the time from the tracheostomy procedure to independent PPV and decannulation was found to be extended. However, the presence of airway disease was not significantly associated with the duration of mechanical ventilation, or with the time to decannulation. The 5-year survival rate was 80.2%; the patients who did not survive died within 12 months of the tracheostomy procedure. CONCLUSION: Infants with moderate or severe bronchopulmonary dysplasia occasionally require tracheostomy tube placement for mechanical ventilation. In cases with airway disease, the time from the tracheostomy procedure to independent PPV and decannulation tended to be increased, although this increase was not significant.

Applied the "Type and Screen" Method Based on Antibody Screening Test Including Di(a) Cells and Immediate Spin Crossmatch to All Patients Who Received Transfusion for Five Years / 대한수혈학회지

BACKGROUND: To prevent a hemolytic transfusion reaction caused by an unexpected antibody, a crossmatch following ABO/Rh typing and antibody screening test is performed before a red cell transfusion. The conventional crossmatch method is usually performed using the room temperature saline method, 37degrees C albumin method, and anti-globulin method. With growth and development of techniques for laboratory and records management, demand for reduction of work load is on the rise, therefore, use of the "type and screen" method and Immediate spin crossmatch as a pretransfusion test is recommended. METHODS: A retrospective analysis was performed using records from the Pusan National University Hospital blood bank from 2008 to 2012. Room temperature saline method omitting the anti-globulin crossmatch has been used in order to issue a compatible red cell product, when antibody screening performed using a cell panel (DiaCell I-II-Dia) in all patients where a request for a red cell transfusion was sent to the blood bank is negative, without previously identified unexpected antibodies. RESULTS: In total, 107,569 units of PRBCs were requested, 100,978 units (93.88%) were issued only immediate-spin crossmatch following type and screen method, and exclusion criteria were indicated in 6.12% of the total. There was no single case where the antibody screen was negative with guarantee of compatibility and hemolytic transfusion reaction occurred. CONCLUSION: The "Type and Screen" method based on antibody screening test including Dia cells and Immediate spin crossmatch application can contribute to safe, efficient transfusion service in the blood bank.

Functional Interaction of HIF-1 and NF-kappaB Increasing the Transcriptional Activation of TNF-alpha Gene in Monocytes / 대한수혈학회지

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine fulfilling a broad variety of immunoregulatory functions. Monocytes and macrophages play a pivotal role in inflammation and immune regulation. NF-kappaB and HIF-1 are known to increase expression of the TNF-alpha gene in a separate way. METHODS: Human monocytic leukemia, U937 cells, were transfected using the standard electroporation method for intracellular expression of NF-kappaB and HIF-1. We performed analysis using the mammalian two-hybrid assay and co-immunoprecipitation assay for detection of protein interaction of both proteins. In addition, chromatin immunoprecipitation analysis was performed for examination of NF-kappaB and HIF-1 binding on the TNF-alpha gene promoter. RESULTS: Here we show that NF-kappaB and HIF-1 cooperatively induced an increase in expression of the TNF-alpha gene dependent on promoter activity by the direct protein interaction of these two transcription factors. Hypoxia signaling induced marked enhancement of the transactivation of TNF-alpha promoter by HIF-1 and NF-kappaB. A tandem NF-kappaB/HIF-1 binding site was identified within the TNF-alpha promoter, which acted as a strong enhancer element. Physical association of the Rel domain of NF-kappaB and the N-TD domain of HIF-1 was required. Hypoxia treatment also resulted in a significant increase in the protein interaction of NF-kappaB and HIF-1 in vivo. Both transcription factors were recruited on the chromatin TNF-alpha promoter dependent on hypoxia stimuli. CONCLUSION: The results of this study indicate that a variety of extracellular signals for activation of TNF-alpha gene expression might converge on the transcriptional regulation through the NF-kappaB/HIF-1 signaling pathway.

Unrecognized C1 Lateral Mass Fracture Without Instability; The Origin of Posterior Neck Pain

Posterior neck pain is a common complaint of patients in the pain clinic. The atlas (C1) burst fracture is known to be a cause of posterior neck pain and instability. Although the atlas burst fracture and instability can be discovered by plain X-rays which show lateral mass displacement or widening of the atlantodental interval, assessment of an atlas burst fracture can be difficult if there is no instability in the imaging study. Here we report a case of a 46-year-old female patient who had complained of sustained posterior neck pain for 6 months. Plain X-rays showed only disc space narrowing at C4/5 and C5/6, without any cervical instability. However, an unrecognized C1 lateral mass fracture was detected by CT and MRI. The patient's pain was then successfully treated after atlantoaxial joint injection with a C2 DRG block.

Cultured human chromaffin cells grafted in spinal subarachnoid space relieves allodynia in a pain rat model / 대한마취과학회지

BACKGROUND: Implantation of xenogenic chromaffin cells into the spinal subarachnoid space can produce analgesia in neuropathic pain models. However, transplantation of xenogeneic chromaffin cell has a potential risk of viral or bacterial infections from animals to humans including encephalopathy due to prion transmission. The aim of this study was to investigate the possibility of developing a homogeneic source of therapeutic chromaffin cells. METHODS: Anti-allodynic effects of human chromaffin cells (HCCs) were evaluated in a neuropathic pain model in rats induced by chronic constriction injury of the sciatic nerve. HCCs encapsulated with alginate-poly-L-lysine-alginate were intrathecally implanted into rats (n = 10), while empty capsules were intrathecally implanted as a control (n = 8). Levels of norepinephrine from encapsulated HCCs before and after nicotinic stimulation were measured. We then perfomed a behavior test (cold allodynia) with acetone. In addition, to assess the potential contribution to pain reduction of opioid peptides released from the HCCs, all animals were injected with naloxone. RESULTS: The concentration of norepinephrine after nicotine stimulation was significantly increased compared to basal levels. Intrathecal implantation of encapsulated HCCs, significantly reduced cold allodynia as compared to rats receiving empty capsules (P < 0.05). Fifteen minutes after the injection of naloxone, cold allodynia significantly decreased in rats with HCCs (P < 0.05), while the degree of cold allodynia in control animals was unaltered. CONCLUSIONS: From these results, it appears that HCCs have a possibility as an analgesic source for transplants delivering pain-reducing neuroactive substances.

The Useful Clinical Indicators of Performing a Spinal Tapping During an Outbreak of Enteroviral Meningitis / 대한소아신경학회지

PURPOSE: Although spinal tapping and cerebrospinal fluid analysis is essential for diagnosis of aseptic meningitis, it is equivocal that all patients with headache and vomiting should receive spinal tapping for diagnosis of meningitis during an outbreak of enteroviral meningitis in summer seasons. The purpose of this study was to find clinical indicators that may be useful for differentiation of bacterial meningitis, and also to compare the clinical course between spinal tapping group and non-spinal tapping group confirmed enteroviral infection. METHODS: We retrospectively reviewed medical record of 65 cases of reverse transcription-polymerase chain reaction(RT-PCR) proven enteroviral meningitis, and 30 cases of culture proven bacterial meningitis admitted in Chunchon Sacred Heart Hospital. We compared the difference of clinical factors between bacterial and enteroviral meningitis groups and also clinical course between spinal tapping and non-spinal tapping groups. RESULTS: Children with bacterial meningitis had younger age onset, high incidence of seizure and altered consciousness, increased C-reactive protein(CRP) levels(P0.05). Children with spinal tapping group with enteroviral meningitis had longer hospital stay and duration of fever as compared to children in non-spinal tapping group(P<0.05), but no difference in duration of headache in both groups. CONCLUSION: We recommend children with younger age, altered consciousness, having seizure and increased CRP levels receive spinal tapping for the differentiation of bacterial meningitis during an outbreak of enteroviral meningitis, and introduction of rapid diagnostic technique may reduce unnecessary spinal tapping, hospital stay and antibiotics therapy.

Inherited metabolic diseases in the urine organic acid analysis of complex febrile seizure patients / 소아과

PURPOSE: Seizure associated with fever may indicate the presence of underlying inherited metabolic diseases. The present study was performed to investigate the presence of underlying metabolic diseases in patients with complex febrile seizures, using analyses of urine organic acids. METHODS: We retrospectively analyzed and compared the results of urine organic acid analysis with routine laboratory findings in 278 patients referred for complex febrile seizure. RESULTS: Of 278 patients, 132 had no abnormal laboratory findings, and 146 patients had at least one of the following abnormal laboratory findings: acidosis (n=58), hyperammonemia (n=55), hypoglycemia (n=21), ketosis (n=12). Twenty-six (19.7%) of the 132 patients with no abnormal findings and 104 (71.2%) of the 146 patients with statistically significant abnormalities showed abnormalities on the organic acid analysis (P<0.05). Mitochondrial respiratory chain disorders (n=23) were the most common diseases found in the normal routine laboratory group, followed by PDH deficiency (n=2 ) and ketolytic defect (n=1). In the abnormal routine laboratory group, mitochondrial respiratory chain disorder (n=29) was the most common disease, followed by ketolytic defects (n=27), PDH deficiency (n=9), glutaric aciduria type II (n=9), 3-methylglutaconic aciduria type III (n=6), biotinidase deficiency (n=5), propionic acidemia (n=4), methylmalonic acidemia (n=2), 3-hydroxyisobutyric aciduria (n=2), orotic aciduria (n=2), fatty acid oxidation disorders (n=2), 2-methylbranched chain acyl CoA dehydrogenase deficiency (n=2), 3-methylglutaconic aciduria type I (n=1), maple syrup urine disease (n=1), isovaleric acidemia (n=1), HMG-CoA lyase deficiency (n=1), L-2-hydroxyglutaric aciduria (n=1), and pyruvate carboxylase deficiency (n=1). CONCLUSION: These findings suggest that urine organic acid analysis should be performed in all patients with complex febrile seizure and other risk factors for early detection of inherited metabolic diseases.

Implication of phosphorylation of the myosin II regulatory light chain in insulin-stimulated GLUT4 translocation in 3T3-F442A adipocytes

In adipocytes, insulin stimulates glucose transport primarily by promoting the translocation of GLUT4 to the plasma membrane. Requirements for Ca2+/ calmodulin during insulin-stimulated GLUT4 translocation have been demonstrated; however, the mechanism of action of Ca2+ in this process is unknown. Recently, myosin II, whose function in non-muscle cells is primarily regulated by phosphorylation of its regulatory light chain by the Ca2+/calmodulin-dependent myosin light chain kinase (MLCK), was implicated in insulin-stimulated GLUT4 translocation. The present studies in 3T3- F442A adipocytes demonstrate the novel finding that insulin significantly increases phosphorylation of the myosin II RLC in a Ca2+-dependent manner. In addition, ML-7, a selective inhibitor of MLCK, as well as inhibitors of myosin II, such as blebbistatin and 2,3-butanedione monoxime, block insulin- stimulated GLUT4 translocation and subsequent glucose transport. Our studies suggest that MLCK may be a regulatory target of Ca2+/calmodulin and may play an important role in insulin-stimulated glucose transport in adipocytes.