Breakage and Disappearance of a Part of the Midline Catheter Tip During Insertion.

Midline catheters have been proposed as alternatives to central venous catheters and peripherally inserted central catheters. Midline catheters reduce the incidence of overall needle stick injuries during hospitalization, have lower complication rates than central venous catheters or peripherally inserted central catheters, and provide potential cost benefits for hospitals. Complications with midline catheters are similar to those of other intravenous catheters, and intravenous catheter breakage is very rare and invasive. We report a case wherein a midline catheter tip was broken during insertion and removed by open surgery. For the safe use of midline catheters, accurate and delicate insertion techniques should be practiced. More case studies are warranted to verify the usefulness and convenience of various types of midline catheters for their universal use.

Immune response to hepatitis B vaccination and factors associated with poor immune response among healthcare workers.

BACKGROUND: Hepatitis B virus (HBV) infection is a major global health problem, and healthcare workers (HCWs) are at high risk for HBV infection. Current guidelines strongly recommend immunization and screening for high-risk groups. AIMS: We evaluated immunization and screening for HBV vaccination, assessed post-vaccination immune status of HCW's and characterized potential risk factors associated with poor immune response. MATERIALS AND METHODS: From January 2010 to December 2018, we retrospectively analyzed comprehensive health checkup data for a total of 303 HCWs who received an HBV vaccination. After vaccination, HBV surface antibody (anti-HBs) titers were collected and the distribution of immune response types was determined. Risk factors for poor immune responses were identified using logistic regression. RESULTS: A total of 213 HCWs were analyzed after exclusion based on the exclusion criteria. In total, 28 (13.2%) HCWs had anti-HBs titers <100 mIU/mL (hyporesponsive/nonresponsive groups), and 185 (86.8%) had anti-HBs titers ≥100 mIU/mL (hyperresponsive group). Follow-up observations found that 75% (21/28) of the hyporesponsive/nonresponsive groups did not have increased anti-HBs titers or did not maintain an increased response. A multivariate analysis showed that HBV antibody titers at the time of employment were a significant risk factor (OR, 6.12; CI, 1.34-27.93; P = 0.019). CONCLUSIONS: More attention should be paid to groups that are hyporesponsive/nonresponsive after vaccination and to those with low anti-HBs titers at the beginning of employment. HCWs can be further protected from HBV if their results are discussed at postvaccination follow-ups.

Dynamic interactions of lactic acid bacteria in Korean sourdough during back-slopping process.

AIMS: This study aimed to clarify the cause of quality reduction in Korean sourdough after successive back-slopping. METHODS AND RESULTS: We investigated the dynamic changes in lactic acid bacteria during the back-slopping process using genetic fingerprinting techniques. During the initial propagation phases, the dominant lactic acid bacteria were Fructilactobacillus sanfranciscensis (<5 log CFU per g sourdough), Latilactobacillus curvatus (9·5 log CFU per g sourdough) and Levilactobacillus brevis (6·5 log CFU per g sourdough). However, after the 11th propagation, F. sanfranciscensis became more prominent (>9·0 log CFU per g sourdough), whereas L. curvatus and L. brevis rapidly decreased. Monitoring these bacteria in the co-culture system revealed that acid-tolerant F. sanfranciscensis rapidly utilized maltose (1·65 g l-1  h-1 ) and produced large amounts of lactic acid, whereas L. brevis and L. curvatus consumed maltose slowly and L. curvatus was poorly tolerant to lactic acid. CONCLUSION: The results indicate that competition exists between the lactic acid bacteria in sourdough during the back-slopping process, and microbial succession by acid-tolerant species results in quality reduction of sourdough. SIGNIFICANCE AND IMPACT OF THE STUDY: This study uncovered the cause of microbial changes during the propagation of Korean sourdough and proposed a strategy to develop starters to produce high-quality bakery products.

Subnanosecond phase transition dynamics in laser-shocked iron.

Iron is one of the most studied chemical elements due to its sociotechnological and planetary importance; hence, understanding its structural transition dynamics is of vital interest. By combining a short pulse optical laser and an ultrashort free electron laser pulse, we have observed the subnanosecond structural dynamics of iron from high-quality x-ray diffraction data measured at 50-ps intervals up to 2500 ps. We unequivocally identify a three-wave structure during the initial compression and a two-wave structure during the decaying shock, involving all of the known structural types of iron (α-, γ-, and ε-phase). In the final stage, negative lattice pressures are generated by the propagation of rarefaction waves, leading to the formation of expanded phases and the recovery of γ-phase. Our observations demonstrate the unique capability of measuring the atomistic evolution during the entire lattice compression and release processes at unprecedented time and strain rate.

Outpatient total shoulder arthroplasty: A cost-identification analysis.

BACKGROUND: As demand for total shoulder arthroplasty (TSA) rises, containing costs will become increasingly important. We hypothesize that performing ambulatory TSA procedures results in significant cost savings. METHODS: A model was created to evaluate cost savings. Hospital stay length and cost, pain control method and cost, and number of annual outpatient TSA procedures were estimated based on literature. RESULTS: Estimated cost savings per patient were $747 to $15,507 (base case $5594), total annual savings of $4.1M to $349M (base case $82M), and ten-year savings of $51M to $5.4B (base case $1.1B). CONCLUSION: Ambulatory TSA procedures result in significant cost savings.

Association between height and periodontitis in Korean adults: Results from KNHANES IV and V.

BACKGROUND AND OBJECTIVE: Evidence shows that a short stature in adulthood is associated with chronic diseases. However, few studies have investigated the association between height and periodontitis. The purpose of this study was to examine the relationship between adult height and periodontitis and to assess the roles of covariates in different birth cohorts of Korea. MATERIAL AND METHODS: This was a cross-sectional study using the data from the 4th and 5th Korea National Health and Nutritional Examination Survey. The subjects were grouped into 2 birth cohorts based on their historical and social context: born from 1946 to 1962 and from 1963 to 1978. The dependent variables were periodontitis and severe periodontitis, while the independent variable was the height quartile. Demographic factors (age and gender), socioeconomic position (own education, region and income), health behaviors (frequency of daily tooth brushing and smoking) and medical status (diabetes) were included. Logistic regression analyses estimated the association of adult height with periodontitis after sequential adjustments. RESULTS: The sample size of the final analysis was 18 010. The shortest quartile was associated with severe periodontitis (OR = 1.55, 95% CI 1.11-2.16) in the 1963-1978 birth cohort. The association remained after full adjustment in the 1963-1978 birth cohort (OR = 1.41, 95% CI 1.01-1.97). CONCLUSION: Our study shows that there is an inverse association between height and severe periodontitis only in the younger Korean birth cohort. Our results support the impact of height, as an early childhood environmental indicator, on severe periodontitis in adulthood.

Clinical, biochemical, and genetic aspects of Sjögren-Larsson syndrome.

Sjögren-Larsson syndrome (SLS) is caused by an autosomal recessive mutation in ALDH3A2, which encodes the fatty aldehyde dehydrogenase responsible for the metabolism of long-chain aliphatic aldehydes and alcohols. The pathophysiologic accumulation of aldehydes in various organs, including the skin, brain, and eyes, leads to characteristic features of ichthyosis, intellectual disability, spastic di-/quadriplegia, and low visual acuity with photophobia. The severity of the clinical manifestations thereof can vary greatly, although most patients are bound to a wheelchair due to contractures. To date, correlations between genotype and phenotype have proven difficult to document due to low disease incidence and high heterogenetic variability in mutations. This review summarizes the clinical characteristics of SLS that have been found to contribute to the prognosis thereof, as well as recent updates from genetic and brain imaging studies. In addition, the differential diagnoses of SLS are briefly illustrated, covering cerebral palsy and other genetic or neurocutaneous syndromes mimicking the syndrome.

Peptide binding to metal oxide nanoparticles.

Magnetic metal oxide nanoparticles demonstrate great applicability in several fields such as biotechnology, medicine and catalysis. A stable, magnetic and low-cost material, nanoscale magnetite, is an interesting adsorbent for protein purification. Downstream processing can account for up to 80% of the total production costs in biotechnological production. As such, the development of new innovative separation methods can be regarded as highly profitable. While short peptide sequences can be used as specific affinity tags for functionalised adsorber surfaces, they need expensive affinity ligands on the particle surface for adsorption. In order to identify peptide tags for several non-functionalised inorganic surfaces, different binding conditions to iron oxide nanoparticles are evaluated. Therefore, magnetite nanoparticles in a range of 5-20 nm were synthesised with a co-precipitation method. Zeta potential measurements indicated an amphiphilic surface with an isoelectric point in the neutral pH region. Glutamic acid-based homo-peptides were used as affinity peptides for the magnetite nanoparticles. We demonstrate a dependence of the binding affinity of the peptides on pH and buffer ions in two different experimental set-ups. The nature of surface coordination for glutamic acid-based peptides can be demonstrated with different spectroscopic approaches such as infrared spectroscopy (IR), Raman spectroscopy and circular dichroism spectroscopy (CD). We want to emphasise the importance of physicochemical properties such as surface energy, polarity, morphology and charge. These parameters, which are dependent on the environmental conditions, play a crucial role in peptide interactions with iron oxide surfaces. The understanding of the adsorption of simple biomolecules on nanoscale metal oxide surfaces also represents the key to the even more complex interactions of proteins at the bio-nano interface. From the identification of interaction patterns and an understanding of the adsorption of these peptides, the up-scaling to tagged model proteins facilitates the possibility of an industrial magnetic separation process and might therefore reduce time and costs in purification processes.

Novel strategy for a bispecific antibody: induction of dual target internalization and degradation.

Activation of the extensive cross-talk among the receptor tyrosine kinases (RTKs), particularly ErbB family-Met cross-talk, has emerged as a likely source of drug resistance. Notwithstanding brilliant successes were attained while using small-molecule inhibitors or antibody therapeutics against specific RTKs in multiple cancers over recent decades, a high recurrence rate remains unsolved in patients treated with these targeted inhibitors. It is well aligned with multifaceted properties of cancer and cross-talk and convergence of signaling pathways of RTKs. Thereby many therapeutic interventions have been actively developed to overcome inherent or acquired resistance. To date, no bispecific antibody (BsAb) showed complete depletion of dual RTKs from the plasma membrane and efficient dual degradation. In this manuscript, we report the first findings of a target-specific dual internalization and degradation of membrane RTKs induced by designed BsAbs based on the internalizing monoclonal antibodies and the therapeutic values of these BsAbs. Leveraging the anti-Met mAb able to internalize and degrade by a unique mechanism, we generated the BsAbs for Met/epidermal growth factor receptor (EGFR) and Met/HER2 to induce an efficient EGFR or HER2 internalization and degradation in the presence of Met that is frequently overexpressed in the invasive tumors and involved in the resistance against EGFR- or HER2-targeted therapies. We found that Met/EGFR BsAb ME22S induces dissociation of the Met-EGFR complex from Hsp90, followed by significant degradation of Met and EGFR. By employing patient-derived tumor models we demonstrate therapeutic potential of the BsAb-mediated dual degradation in various cancers.

A genome-wide association study of antidepressant response in Koreans.

We conducted a three-stage genome-wide association study (GWAS) of response to antidepressant drugs in an ethnically homogeneous sample of Korean patients in untreated episodes of nonpsychotic unipolar depression, mostly of mature onset. Strict quality control was maintained in case selection, diagnosis, verification of adherence and outcome assessments. Analyzed cases completed 6 weeks of treatment with adequate plasma drug concentrations. The overall successful completion rate was 85.5%. Four candidate single-nucleotide polymorphisms (SNPs) on three chromosomes were identified by genome-wide search in the discovery sample of 481 patients who received one of four allowed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs (Stage 1). In a focused replication study of 230 SSRI-treated patients, two of these four SNP candidates were confirmed (Stage 2). Analysis of the Stage 1 and Stage 2 samples combined (n = 711) revealed GWAS significance (P = 1.60 × 10(-8)) for these two SNP candidates, which were in perfect linkage disequilibrium. These two significant SNPs were confirmed also in a focused cross-replication study of 159 patients treated with the non-SSRI antidepressant drug mirtazapine (Stage 3). Analysis of the Stage 1, Stage 2 and Stage 3 samples combined (n = 870) also revealed GWAS significance for these two SNPs, which was sustained after controlling for gender, age, number of previous episodes, age at onset and baseline severity (P = 3.57 × 10(-8)). For each SNP, the response rate decreased (odds ratio=0.31, 95% confidence interval: 0.20-0.47) as a function of the number of minor alleles (non-response alleles). The two SNPs significantly associated with antidepressant response are rs7785360 and rs12698828 of the AUTS2 gene, located on chromosome 7 in 7q11.22. This gene has multiple known linkages to human psychological functions and neurobehavioral disorders. Rigorous replication efforts in other ethnic populations are recommended.

Comparison of the efficacy of tenofovir and entecavir for the treatment of nucleos(t) ide-naïve patients with chronic hepatitis B.

BACKGROUND: An important goal in the treatment of chronic hepatitis B virus (HBV) infection is to prevent hepatocellular carcinoma and liver cirrhosis by suppressing HBV replication. Tenofovir and entecavir are effective viral suppression compounds. However, comparative data is scant, especially in Korea. This study compared tenofovir and entecavir concerning efficiencies and side effects. MATERIALS AND METHODS: We retrospectively reviewed data of nucleos (t) ide-naïve patients with chronic HBV infection. Independent variables reflecting virological response were evaluated, and the decline in serum HBV DNA levels, and side effects between tenofovir-and entecavir-treated patients were compared at treatment week 12, 24, and 48. RESULTS: At the end of 48 weeks, there was no statistical difference in the induction of undetectable levels of HBV DNA between the entecavir (82.5%) and tenofovir (69.2%) groups. Entecavir was more effective in reducing serum HBV DNA levels at 24 weeks of treatment (serum HBV DNA decline of 5.53 and 4.95 log10 units for entecavir and tenofovir, respectively; P=0.044), but the rate of decline was similar at other weeks. There was no difference between the two groups in terms of side effects and discontinuance of treatment due to side effects. CONCLUSIONS: Tenofovir is not significantly different from entecavir in virologic response and tolerability in the treatment of chronic HBV.

Comparative Transcriptome Analysis of Cell-Free Fetal RNA from Amniotic Fluid and RNA from Amniocytes in Uncomplicated Pregnancies.

OBJECTIVES: We aimed to compare tissue-specific expression profiles and biological pathways of RNA from amniocytes and amniotic fluid supernatant (AFS) from second-trimester pregnancies by using transcriptome analysis. Additionally, we wanted to explore whether cell-free RNA from AFS exhibits a unique gene expression signature that more adequately reflects the fetal developmental process than amniocyte RNA. METHODS: Amniotic fluid samples were prospectively collected in the second trimester of pregnancy from euploid fetuses. Total RNA was extracted from amniocytes and AFS and hybridized to Affymetrix GeneChip Human Arrays. Significantly differentially expressed transcripts between amniocytes and AFS were obtained by using Welch's t-test. Unsupervised hierarchical clustering was used to visualize overall expression characteristics and differences in transcripts between AFS and amniocytes. The biological functions of selected genes were analyzed using various online Gene Ontology databases. RESULTS: A total of 3,072 and 15,633 transcripts were detected in the second-trimester AFS and amniocytes, respectively. Hierarchical clustering revealed differential transcript expression between AFS and amniocytes. We found 353 genes that were specifically enriched in the AFS only, and tissue expression analysis showed enrichment of brain-specific genes in the AFS. Biological pathway analysis revealed that AFS-specific transcripts were mainly involved in embryonic development, cardiovascular development, and cellular morphology pathways. CONCLUSION: This study demonstrated differential tissue-specific gene expression profiles and biological pathways between AFS and amniocytes. The results suggested that AFS is the preferred RNA source to investigate potential biomarkers of fetal neurodevelopment.

Use of vertebral body units to locate the cavoatrial junction for optimum central venous catheter tip positioning.

BACKGROUND: Central venous catheter (CVC) placement plays an important role in clinical practice; however, optimal positioning of the CVC tip remains a controversial issue. The objective of this study was to evaluate the use of vertebral body unit (VBUs), to locate the cavoatrial junction (CAJ), for optimal CVC tip placement based on chest radiography (CXR) using the carina as a landmark. METHODS: 524 patients who underwent coronary computed tomographic angiography (CTA) and CXR were included. The position of the CAJ was identified using VBUs, and the efficacy of VBUs for locating the CAJ with the carina as a landmark was analysed using multiple regression analysis. A VBU was defined as the distance between two adjacent vertebral bodies, including the inter-vertebral disk space. RESULTS: The mean (sd) distance from the carina to the superior CAJ was 54.3 (9.7) mm on CTA; the mean distance in VBUs at the level of the carina was 21.4 (1.7) mm on CTA and 22.6 (2.1) mm on CXR. The mean CAJ position was 2.5 VBUs below the carina on CTA and 2.4 VBUs below on CXR with 95% limits of agreement between -0.6 and +0.3. CONCLUSIONS: The position of the CVC tip in relation to the carina can be described using the thoracic spine as an internal ruler, and the position of the CAJ in adults was reliably estimated to be 2.4 VBUs below the carina. CLINICAL TRIAL REGISTRATION: KCT0001319.

Pulmonary nodule size evaluation with chest tomosynthesis and CT: a phantom study.

OBJECTIVE: We compared digital tomosynthesis (TOMO) and chest CT in terms of assessing the sizes of nodules located in zones where evaluation by simple radiography is limited. METHODS: A total of 48 images comprising phantom nodules of four sizes in six different locations were used. Nodule size measurement errors for measurements using TOMO and CT images compared with the actual size from each observer were calculated. The inter- and intraobserver repeatability of the measured values and the agreement between the two techniques were assessed using the method described by Bland and Altman. RESULTS: The mean measurement errors for all of the nodules and four observers were -0.84 mm [standard deviation (SD), 0.60 mm] on TOMO and -0.18 mm (SD, 0.71 mm) on CT images. The mean measurement errors for the different observers ranged from -1.11 to -0.55 mm for TOMO and from -0.39 to 0.08 mm for CT. Assessing the agreement between nodule size measurements using TOMO and CT resulted in mean measurement errors of -0.65 mm, with a 95% limit of agreement of -2.53 to 1.22 mm for comparison of TOMO with CT. CONCLUSION: Our results suggest that nodule sizes obtained using TOMO and chest CT are comparable, even for nodules located in areas where the size measurement is limited on simple radiography. ADVANCES IN KNOWLEDGE: TOMO and CT can be used interchangeably, even for nodules located in a blind area on simple radiography.

Semi-quantitative HPV viral load in patients with ASC-US cytology: viral load correlates strongly with the presence of CIN but only weakly with its severity.

OBJECTIVES: This study was performed to evaluate the prognostic significance of human papillomavirus (HPV) viral load, expressed in relative light units (RLUs), in patients with atypical squamous cells of undetermined significance (ASC-US) cytology. METHODS: A total of 349 ASC-US cases with HPV infection, detected using Hybrid Capture 2, were diagnosed histologically. A colposcopically directed punch biopsy was performed on acetowhite areas. Endocervical curettage biopsy and random cervical punch biopsy in four quadrants were performed in unsatisfactory colposcopy cases. In negative colposcopy cases, random cervical punch biopsy in four quadrants was performed. RESULTS: Case with no cervical intraepithelial neoplasia (CIN), CIN1 and CIN2+ (CIN2/CIN3) accounted for 162, 135 and 52 cases, respectively. The mean age showed no difference among the three groups (P = 0.510). There was a significant correlation between RLU values and the presence of CIN (P < 0.001), but less so with its severity: the median RLU values for negative, CIN1 and CIN2+ cases were 42.68, 146.45 and 156.43, respectively, with widely overlapping confidence intervals. The cut-off values of RLU to detect CIN1+ and CIN2+ were 6.73 and 45.64, respectively. CONCLUSIONS: The HPV viral load in ASC-US cases showed a significant correlation with the presence of CIN and less so with its severity, and showed large overlap of viral loads between grades of CIN. In ASC-US cases, RLU was not an accurate predictor of immediate high-grade CIN.

Metabolic tumour volume and total lesion glycolysis, measured using preoperative 18F-FDG PET/CT, predict the recurrence of endometrial cancer.

OBJECTIVE: To investigate the prognostic value of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), measured by preoperative positron emission tomography and computerised tomography (PET/CT), in women with endometrial cancer. DESIGN: Retrospective cohort study. SETTING: A tertiary referral centre. POPULATION: Women with endometrial cancer who underwent preoperative (18)F-FDG PET/CT in the period 2004-2009. METHODS: Clinicopathological data for 84 women with endometrial cancer were reviewed from medical records. Cox proportional hazards modelling identified recurrence predictors. The receiver operating characteristic (ROC) curve was used to determine the cut-off value for predicting recurrence. MAIN OUTCOME MEASURE: Disease-free survival (DFS). RESULTS: The number of patients with International Federation of Gynecology and Obstetrics (FIGO) stages were: I (58); II (11); III (13); and IV (2). The median DFS was 48 (1-85) months. By univariate analysis, DFS was significantly associated with FIGO stage, histology, peritoneal cytology, myometrial invasion, nodal metastasis, serum CA-125, MTV, and TLG. Using multivariate analysis, the MTV (P = 0.010; hazard ratio, HR = 1.010; 95% confidence interval, 95% CI = 1.002-1.018) and TLG (P = 0.024; HR = 1.001; 95% CI = 1.000-1.002) were associated with DFS. The area under the ROC curve was 0.679 (95% CI = 0.505-0.836) after discriminating for recurrence using an MTV cut-off value of 17.15 ml. Regarding TLG, the cut-off value was 56.43 g and the area under the ROC plot was 0.661 (95% CI = 0.501-0.827). Kaplan-Meier survival graphs demonstrated a significant difference in DFS between groups categorised using the cut-off values for MTV and TLG (P < 0.022 for MTV and P < 0.047 for TLG, by log-rank test). CONCLUSIONS: Preoperative MTV and TLG could be independent prognostic factors predicting the recurrence of endometrial cancer.

Preoperative nomogram for the identification of lymph node metastasis in early cervical cancer.

BACKGROUND: The objective of this study is to construct a preoperative nomogram predicting lymph node metastasis (LNM) in early-cervical cancer patients. METHODS: Between 2009 and 2012, 493 early-cervical cancer patients received hysterectomy and pelvic/para-aortic lymphadenectomy. Patients who were diagnosed during 2009-2010 were assigned to a model-development cohort (n=304) and the others were assigned to a validation cohort (n=189). A multivariate logistic model was created from preoperative clinicopathologic data, from which a nomogram was developed and validated. A predicted probability of LNM<5% was defined as low risk. RESULTS: Age, tumour size assessed by magnetic resonance imaging, and LNM assessed by positron emission tomography/computed tomography were independent predictors of nodal metastasis. The nomogram incorporating these three predictors demonstrated good discrimination and calibration (concordance index=0.878; 95% confidence interval (CI), 0.833-0.917). In the validation cohort, the discrimination accuracy was 0.825 (95% CI, 0.736-0.895). In the model-development cohort, 34% of them were classified as low risk and negative predictive value (NPV) was 99.0%. In the validation cohort, 38% were identified as low risk and NPV was 95.8%. Integrating the model-development and validation cohorts, negative likelihood ratio was 0.094 (95% CI, 0.036-0.248). CONCLUSION: A robust nomogram predicting LNM in early cervical cancer was developed. This model may improve clinical trial design and help physicians to decide whether lymphadenectomy should be performed.

Histone deacetylase inhibitors suppress coxsackievirus B3 growth in vitro and myocarditis induced in mice.

UNLABELLED: Clinical importance of myocarditis, predominantly caused by coxsackievirus B3 (CVB3), is recently rising. However, a detailed mechanism of pathogenesis of CVB3 myocarditis still needs to be clarified. Recently, it has been reported that histone modifications including acetylation are involved in coxsackievirus replication. To examine whether the CVB3 replication requires histone acetylation, histone deacetylase (HDAC) inhibitors were employed. We found that the HDAC2 activity increased in virus-infected cells at 12 hrs p.i. and that HDAC inhibitors suppressed the virus replication in vitro. This suggests that the HDAC2 activity may be required for the virus replication. Eventually, a HDAC inhibitor trichostatin A protected against CVB3-induced myocardial injury in vivo. Our results suggest that HDAC may be a novel therapeutic target for treating viral myocarditis. KEYWORDS: coxsackievirus B3; histone acetyltransferase; histone deacetylase; HDAC inhibitors, trichostatin A; apicidin; valproic acid; shRNA; myocarditis; mouse.