DIRECTEUR: transcriptome-based prediction of small molecules that replace transcription factors for direct cell conversion.

MOTIVATION: Direct reprogramming (DR) is a process that directly converts somatic cells to target cells. Although DR via small molecules is safer than using transcription factors (TFs) in terms of avoidance of tumorigenic risk, the determination of DR-inducing small molecules is challenging. RESULTS: Here we present a novel in silico method, DIRECTEUR, to predict small molecules that replace TFs for DR. We extracted DR-characteristic genes using transcriptome profiles of cells in which DR was induced by TFs, and performed a variant of simulated annealing to explore small molecule combinations with similar gene expression patterns with DR-inducing TFs. We applied DIRECTEUR to predicting combinations of small molecules that convert fibroblasts into neurons or cardiomyocytes, and were able to reproduce experimentally verified and functionally related molecules inducing the corresponding conversions. The proposed method is expected to be useful for practical applications in regenerative medicine. AVAILABILITY AND IMPLEMENTATION: The code and data are available at the following link: https://github.com/HamanoLaboratory/DIRECTEUR.git.

Utility of human cytochrome P450 inhibition data in the assessment of drug-induced liver injury.

1. Drug-induced liver injury (DILI) is a major cause of drug development discontinuation and drug withdrawal from the market, but there are no golden standard methods for DILI risk evaluation. Since we had found the association between DILI and CYP1A1 or CYP1B1 inhibition, we further evaluated the utility of cytochrome P450 (P450) inhibition assay data for DILI risk evaluation using decision tree analysis.2. The inhibitory activity of drugs with DILI concern (DILI drugs) and no DILI concern (no-DILI drugs) against 10 human P450s was assessed using recombinant enzymes and luminescent substrates. The drugs were also subjected to cytotoxicity assays and high-content analysis using HepG2 cells. Molecular descriptors were calculated by alvaDesc.3. Decision tree analysis was performed with the data obtained as variables with or without P450-inhibitory activity to discriminate between DILI drugs and no-DILI drugs. The accuracy was significantly higher when P450-inhibitory activity was included. After the decision tree discrimination, the drugs were further discriminated with the P450-inhibitory activity. The results demonstrated that many false-positive and false-negative drugs were correctly discriminated by using the P450 inhibition data.4. These results suggest that P450 inhibition assay data are useful for DILI risk evaluation.

The Effects of Endoplasmic Reticulum Stress via Intratracheal Instillation of Water-Soluble Acrylic Acid Polymer on the Lungs of Rats.

Polyacrylic acid (PAA), an organic chemical, has been used as an intermediate in the manufacture of pharmaceuticals and cosmetics. It has been suggested recently that PAA has a high pulmonary inflammatory and fibrotic potential. Although endoplasmic reticulum stress is induced by various external and intracellular stimuli, there have been no reports examining the relationship between PAA-induced lung injury and endoplasmic reticulum stress. F344 rats were intratracheally instilled with dispersed PAA (molecular weight: 269,000) at low (0.5 mg/mL) and high (2.5 mg/mL) doses, and they were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure. PAA caused extensive inflammation and fibrotic changes in the lungs' histopathology over a month following instillation. Compared to the control group, the mRNA levels of endoplasmic reticulum stress markers Bip and Chop in BALF were significantly increased in the exposure group. In fluorescent immunostaining, both Bip and Chop exhibited co-localization with macrophages. Intratracheal instillation of PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA with molecular weight 269,000 may lead to pulmonary disorder. Furthermore, the presence of endoplasmic reticulum stress in macrophages was suggested to be involved in PAA-induced lung injury.

Small compound-based direct cell conversion with combinatorial optimization of pathway regulations.

MOTIVATION: Direct cell conversion, direct reprogramming (DR), is an innovative technology that directly converts source cells to target cells without bypassing induced pluripotent stem cells. The use of small compounds (e.g. drugs) for DR can help avoid carcinogenic risk induced by gene transfection; however, experimentally identifying small compounds remains challenging because of combinatorial explosion. RESULTS: In this article, we present a new computational method, COMPRENDRE (combinatorial optimization of pathway regulations for direct reprograming), to elucidate the mechanism of small compound-based DR and predict new combinations of small compounds for DR. We estimated the potential target proteins of DR-inducing small compounds and identified a set of target pathways involving DR. We identified multiple DR-related pathways that have not previously been reported to induce neurons or cardiomyocytes from fibroblasts. To overcome the problem of combinatorial explosion, we developed a variant of a simulated annealing algorithm to identify the best set of compounds that can regulate DR-related pathways. Consequently, the proposed method enabled to predict new DR-inducing candidate combinations with fewer compounds and to successfully reproduce experimentally verified compounds inducing the direct conversion from fibroblasts to neurons or cardiomyocytes. The proposed method is expected to be useful for practical applications in regenerative medicine. AVAILABILITY AND IMPLEMENTATION: The code supporting the current study is available at the http://labo.bio.kyutech.ac.jp/~yamani/comprendre. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Comparison of radial, dorsalis pedis, and posterior tibial arteries for ultrasound-guided arterial catheterisation with dynamic needle tip positioning in paediatric patients: a randomised controlled trial.

BACKGROUND: Arterial catheterisation in children can be challenging and time-consuming. We aimed to compare the success rates of ultrasound-guided arterial catheterisation utilising the short-axis out-of-plane approach with dynamic needle tip positioning in the radial, dorsalis pedis, and posterior tibial arteries in paediatric patients. We also examined the factors influencing the catheterisation success using dynamic needle tip positioning. METHODS: Paediatric patients (aged <3 yr) undergoing cardiac surgery were randomly assigned to three groups based on puncture sites: radial artery (Group R), dorsalis pedis artery (Group D), and posterior tibial artery (Group P). The first-attempt and overall success rates of arterial catheterisation were compared, followed by multiple logistic regression analysis (dependent variable: first-attempt success; independent variables: body weight, diameter and depth of the artery, targeted artery, and trisomy 21). RESULTS: The study included 270 subjects (n=90 per group). There was no significant difference in the first-attempt (Group R: 82%, Group D: 76%, and Group P: 81%) and overall success rates (Group R: 94%, Group D: 93%, and Group P: 91%) among the three groups. The diameter of the artery (per 0.1 mm) (odds ratio: 1.32, 95% confidence interval: 1.09-1.60) and trisomy 21 (odds ratio: 0.43, 95% confidence interval: 0.20-0.92) were independent predictors of first-attempt success or failure. CONCLUSION: The first-attempt and overall success rates of arterial catheterisation of the dorsalis pedis and posterior tibial arteries were not inferior to those in the radial artery when using dynamic needle tip positioning. These two lower extremity peripheral arteries present viable alternative catheterisation sites in paediatric patients. CLINICAL TRIAL REGISTRATION: UMIN000042847.

Ultrasound-Guided Short-Axis Out-of-Plane Approach With or Without Dynamic Needle-Tip Positioning for Peripheral Venous Catheterization in Pediatric Patients: A Systematic Review With Network Meta-Analysis.

OBJECTIVES: To compare the efficacy of the ultrasound-guided approach with and without dynamic needle-tip positioning and the palpation technique regarding success for peripheral venous catheterization in children. DESIGN: A systematic review with network meta-analysis. SETTING: Databases of MEDLINE (via PubMed) and Cochrane Central Register of Controlled Trials. PARTICIPANTS: Patients (<18 years) undergoing peripheral venous catheter insertion. INTERVENTIONS: Randomized clinical trials were included to compare the following techniques: the ultrasound-guided short-axis out-of-plane approach with dynamic needle-tip positioning, the approach without dynamic needle-tip positioning, and the palpation technique. MEASUREMENTS AND MAIN RESULTS: The outcomes were first-attempt and overall success rates. Eight studies were included in the qualitative analyses. According to the estimate of network comparison, dynamic needle-tip positioning was associated with higher first-attempt (risk ratio [RR] 1.67; 95% CI 1.33-2.09) and overall success rates (RR 1.25; 95% CI 1.08-1.44) than palpation. The approach without dynamic needle-tip positioning was not associated with higher first-attempt (RR 1.17; 95% CI 0.91-1.49) and overall success rates (RR 1.10; 95% CI 0.90-1.33) than palpation. Compared to the approach without dynamic needle-tip positioning, dynamic needle-tip positioning was associated with a higher first-attempt success rate (RR 1.43; 95% CI 1.07-1.92), but not a higher overall success rate (RR 1.14; 95% CI 0.92-1.41). CONCLUSIONS: Dynamic needle-tip positioning is efficacious for peripheral venous catheterization in children. It would be better to include dynamic needle-tip positioning for the ultrasound-guided short-axis out-of-plane approach.

Influence of maternal position during combined spinal-epidural anesthesia for labor analgesia on technical difficulties and complications.

PURPOSE: Generally, combined spinal-epidural anesthesia (CSEA) for labor analgesia is performed in the lateral or sitting position; however, only few studies have investigated the effect of maternal position on labor analgesia induction. We aimed to retrospectively assess the influence of maternal position on induction time and complications. METHODS: We retrospectively analyzed anesthetic and medical records regarding labor analgesia in 201 parturients treated between January 2019 and November 2019. Patients were classified into 2 groups based on their position (sitting or lateral) during induction. The primary outcome was the time required for CSEA induction. We compared 2 groups on the primary outcome and the occurrences of other complications during CSEA induction using hyperbaric bupivacaine. Moreover, we performed multiple linear regression analysis to identify independent factors associated with induction time. RESULTS: There was no significant between-group difference in the time required for induction. Multiple linear regression analysis revealed an independent association of the distance from the skin to the epidural space with the time required for induction. The lateral group had a significantly higher incidence of paresthesia than the sitting group (P = 0.028). The lateral group had a significantly higher ephedrine requirement (P < 0.001) than the sitting group. CONCLUSION: Maternal position was not associated with the time required for CSEA induction. However, the sitting group had a lower paresthesia occurrence and ephedrine requirement than the lateral group. Other technical complications were not associated with maternal position during CSEA induction.

New intra-conduit thrombus detected using transesophageal echocardiography immediately after weaning from cardiopulmonary bypass during the Fontan procedure: a case report.

This study reports a case wherein a new thrombus was detected by transesophageal echocardiography in the conduit during extracardiac conduit Fontan procedure. Immediately after weaning from the cardiopulmonary bypass and administration of protamine, a thrombus was noted in the conduit by transesophageal echocardiography. Since the patient was hemodynamically stable, anticoagulation therapy was initiated after admission to the intensive care unit. One week post-surgery, imaging results showed residual thrombus, but the patient was safely discharged. Even during Fontan procedure, careful observation with transesophageal echocardiography is important because of the possibility of thrombus formation in the conduit.

Incidence of catheter-related bloodstream infections following ultrasound-guided central venous catheterization: a systematic review and meta-analysis.

BACKGROUND: Ultrasonographic guidance is widely used for central venous catheterization. Several studies have revealed that ultrasound-guided central venous catheterization increases the rate of success during the first attempt and reduces the procedural duration when compared to the anatomical landmark-guided insertion technique, which could result in protection from infectious complications. However, the effect of ultrasound-guided central venous catheterization on catheter-related bloodstream infections remains unclear. We aimed to conduct a systematic review and meta-analysis to evaluate the value of ultrasound guidance in preventing catheter-related bloodstream infections and catheter colonization associated with central venous catheterization. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE (via PubMed) were searched up to May 9, 2022 for randomized controlled trials (RCTs) comparing ultrasound-guided and anatomical landmark-guided insertion techniques for central venous catheterization. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool for RCTs. A meta-analysis was performed for catheter-related bloodstream infections and catheter colonization, as primary and secondary outcomes, respectively. RESULTS: Four RCTs involving 1268 patients met the inclusion criteria and were analyzed. Ultrasound-guided central venous catheterization was associated with a slightly lower incidence of catheter-related bloodstream infections (risk ratio, 0.46; 95% confidence interval [CI], 0.16-1.32) and was not associated with a lower incidence of catheter colonization (risk ratio, 1.36; 95% CI, 0.57-3.26). CONCLUSION: Ultrasound-guided central venous catheterization might reduce the incidence of catheter-related bloodstream infections. Additional RCTs are necessary to further evaluate the value of ultrasound guidance in preventing catheter-related bloodstream infections with central venous catheterization.

Inflammogenic effect of polyacrylic acid in rat lung following intratracheal instillation.

BACKGROUND: Some organic chemicals are known to cause allergic disorders such as bronchial asthma and hypersensitivity pneumonitis, and it has been considered that they do not cause irreversible pulmonary fibrosis. It has recently been reported, however, that cross-linked acrylic acid-based polymer, an organic chemical, might cause serious interstitial lung diseases, including pulmonary fibrosis. We investigated whether or not intratracheal instillation exposure to cross-linked polyacrylic acid (CL-PAA) can cause lung disorder in rats. METHODS: Male F344 rats were intratracheally instilled with dispersed CL-PAA at low (0.2 mg/rat) and high (1.0 mg/rat) doses, and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure to examine inflammatory and fibrotic responses and related gene expressions in the lungs. Rat lungs exposed to crystalline silica, asbestos (chrysotile), and NiO and CeO2 nanoparticles were used as comparators. RESULTS: Persistent increases in total cell count, neutrophil count and neutrophil percentage, and in the concentration of the cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and C-X-C motif chemokine 5 (CXCL5), which correlated with lung tissue gene expression, were observed in bronchoalveolar lavage fluid (BALF) from 3 days until at least 1 month following CL-PAA intratracheal instillation. Persistent increases in heme oxygenase-1 (HO-1) in the lung tissue were also observed from 3 days to 6 months after exposure. Histopathological findings of the lungs demonstrated that extensive inflammation at 3 days was greater than that in exposure to silica, NiO nanoparticles and CeO2 nanoparticles, and equal to or greater than that in asbestos (chrysotile) exposure, and the inflammation continued until 1 month. Fibrotic changes also progressed after 1 month postexposure. CONCLUSION: Our results suggested that CL-PAA potentially causes strong neutrophil inflammation in the rat and human lung.

Diffusion-Weighted Imaging Hyperintensities in Acute and Subacute-Phase Intracerebral Hemorrhage.

OBJECTIVE: Diffusion-weighted imaging hyperintensities are observed in intracerebral hemorrhage patients at times and might be associated with unfavorable functional outcomes. However, the suitable time to evaluate diffusion-weighted imaging hyperintensities to influence stroke outcome remains unclear. This study investigated the associations between acute and sub-acute diffusion-weighted imaging hyperintensities and functional outcomes among patients with acute intracerebral hemorrhage. METHODS: Diffusion-weighted imaging hyperintensities were evaluated within 24 h (acute phase) and at 14 ± 5 days (sub-acute phase). An unfavorable functional outcome was a score of 5-6 on the modified Rankin Scale at 3 months. RESULTS: Among 268 intracerebral hemorrhage patients, diffusion-weighted imaging hyperintensities in the acute phase were observed in 32 (11.9%). Among 227 patients who underwent a second magnetic resonance imaging in the sub-acute phase, diffusion-weighted imaging hyperintensities were observed in 57 (25.1%). Multivariable analysis revealed that the baseline intracerebral hemorrhage volume, history of stroke, and severe white matter lesions were associated with sub-acute diffusion-weighted imaging hyperintensities. The patients with unfavorable outcomes (n = 37) had a higher frequency of sub-acute diffusion-weighted imaging hyperintensities than those without (n = 190) (51.4% vs. 20.0%, P < 0.001); the frequencies of acute diffusion-weighted imaging hyperintensities were not significantly different between the groups (13.5% vs. 10.0%, P = 0.559). Sub-acute diffusion-weighted imaging hyperintensities were independently associated with unfavorable outcomes after adjusting for confounding factors (Odds Ratio, 3.35, 95% CI 1.20-9.35, P = 0.021). CONCLUSION: The rate of sub-acute diffusion-weighted imaging hyperintensities was higher than acute diffusion-weighted imaging hyperintensities among acute intracerebral hemorrhage patients and likely to be associated with unfavorable outcomes.

Effect of Different Molecular Weights of Polyacrylic Acid on Rat Lung Following Intratracheal Instillation.

BACKGROUND: We conducted intratracheal instillations of different molecular weights of polyacrylic acid (PAA) into rats in order to examine what kinds of physicochemical characteristics of acrylic acid-based polymer affect responses in the lung. METHODS: F344 rats were intratracheally exposed to a high molecular weight (HMW) of 598 thousand g/mol or a low molecular weight (LMW) of 30.9 thousand g/mol PAA at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months post exposure. RESULTS: HMW PAA caused persistent increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 3 months and 6 months following instillation. On the other hand, LMW PAA caused only transient increases in neutrophil influx, CINC in BALF, and HO-1 in the lung tissue from 3 days to up to 1 week or 1 month following instillation. Histopathological findings of the lungs demonstrated that the extensive inflammation and fibrotic changes caused by the HMW PAA was greater than that in exposure to the LMW PAA during the observation period. CONCLUSION: HMW PAA induced persistence of lung disorder, suggesting that molecular weight is a physicochemical characteristic of PAA-induced lung disorder.

Crosslinked Structure of Polyacrylic Acid Affects Pulmonary Fibrogenicity in Rats.

We conducted intratracheal instillations of polyacrylic acid (PAA) with crosslinking and non-crosslinking into rats in order to examine what kinds of physicochemical characteristics of acrylic-acid-based polymers affect responses in the lung. F344 rats were intratracheally exposed to similar molecular weights of crosslinked PAA (CL-PAA) (degree of crosslinking: ~0.1%) and non-crosslinked PAA (Non-CL-PAA) at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months post-exposure. Both PAAs caused increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 6 months following instillation. The release of lactate dehydrogenase (LDH) activity in the BALF was higher in the CL-PAA-exposed groups. Histopathological findings of the lungs demonstrated that the extensive fibrotic changes caused by CL-PAA were also greater than those in exposure to the Non-CL- PAA during the observation period. CL-PAA has more fibrogenicity of the lung, suggesting that crosslinking may be one of the physicochemical characteristic factors of PAA-induced lung disorder.

Intraoperative Diagnosis of a Stuck Bioprosthetic Valve Leaflet Due to a Loop of Suture After Mitral Valve Replacement.

A stuck mechanical valve leaflet is a well-known cardiovascular complication; however, a stuck bioprosthetic valve is a rare but potentially fatal complication. Herein a case of stuck bioprosthetic mitral valve caused by a loop of suture, which was detected on intraoperative 3-dimensional (3D) transesophageal echocardiography immediately after cardiopulmonary bypass, is presented. Restricted motion of the 2 leaflets during diastole and incomplete coaptation during systole were observed clearly on 3D imaging. Thus, intraoperative 3D transesophageal echocardiography imaging is useful for detecting such complications immediately after cardiopulmonary bypass.

Application of cytochrome P450 reactivity on the characterization of chemical compounds and its association with repeated-dose toxicity.

Repeated-dose toxicity (RDT) studies are one of the critical studies to assess chemical safety. There have been some studies attempting to predict RDT endpoints based on chemical substructures, but it remains very difficult to establish such a method, and a more detailed characterization of chemical compounds seems necessary. Cytochrome P450s (P450s) comprise multiple forms with different substrate specificities and play important roles in both the detoxification and metabolic activation of xenobiotics. In this study, we investigated possible use of P450 reactivity of chemical compounds to classify the compounds. A total of 148 compounds with available rat RDT test data were used as test compounds and subjected to inhibition assays against 18 human and rat P450s. Among the tested compounds, 82 compounds inhibited at least one P450 form. Hierarchical clustering analyses using the P450 inhibitory profiles divided the 82 compounds into nine groups, some of which showed characteristic chemical and biological properties. Principal component analyses of the P450 inhibition data in combination with the calculated chemical descriptors demonstrated that P450 inhibition data were plotted differently than most chemical descriptors in the loading plots. Finally, association analyses between P450 inhibition and RDT endpoints showed that some endpoints related to the liver, kidney and hematology were significantly associated with the inhibition of some P450s. Our present results suggest that the P450 reactivity profiles can be used as novel descriptors for characterizing chemical compounds for the investigation of the toxicity mechanism and/or the establishment of a toxicity prediction model.

Ultrasound-guided peripheral vascular catheterization in pediatric patients: a narrative review.

Peripheral vascular catheterization (PVC) in pediatric patients is technically challenging. Ultrasound guidance has gained the most interest in perioperative and intensive care fields because it visualizes the exact location of small target vessels and is less invasive than other techniques. There have been a growing number of studies related to ultrasound guidance for PVC with or without difficult access in pediatric patients, and most findings have demonstrated its superiority to other techniques. There are various ultrasound guidance approaches, and a comprehensive understanding of the basics, operator experience, and selection of appropriate techniques is required for the successful utilization of this technique. This narrative review summarizes the literature regarding ultrasound-guided PVC principles, approaches, and pitfalls to improve its clinical performance in pediatric settings.

Occurrence and Risk Factors for Unplanned Catheter Removal in a PICU: Central Venous Catheters Versus Peripherally Inserted Central Venous Catheters.

OBJECTIVES: We aimed to identify the occurrence and risk factors for unplanned catheter removal due to catheter-associated complications and the effects on catheter survival probability in a PICU. DESIGN: Retrospective, single-center, observational study of cases involving conventional central venous catheters or peripherally inserted central venous catheters. SETTING: The PICU of a tertiary children's hospital. PATIENTS: Consecutive PICU patients with central venous catheters between April 2016 and February 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified unplanned catheter removals that were related to central line-associated bloodstream infection, thrombosis, and mechanical complications. During the study period, 582 central venous catheters and 474 peripherally inserted central venous catheters were identified. The median durations of catheter placement were 4.0 days for central venous catheters and 13.0 days for peripherally inserted central venous catheters (p < 0.001), and unplanned catheter removals due to catheter-associated complications were in 52 (8.9%) central venous catheter cases and 132 (27.8%) peripherally inserted central venous catheter cases (p < 0.001) (15.0 and 16.0 per 1,000 catheter-days, respectively [p = 0.75]). Unplanned catheter removal was associated with a peripheral catheter tip position among both central venous catheters and peripherally inserted central venous catheters (p < 0.001 and p = 0.001), and it was associated with surgical patient status among peripherally inserted central venous catheters (p = 0.009). In contrast, the use of ultrasound-guided insertion was associated with a lower occurrence of unplanned catheter removal among peripherally inserted central venous catheters (p = 0.01). With regard to catheter survival probability, there was no significant difference between central venous catheters and peripherally inserted central venous catheters (p = 0.23). However, peripherally inserted central venous catheters had a lower occurrence of central line-associated bloodstream infection than central venous catheters (p = 0.03), whereas there was no significant difference in the rates of thrombosis (p = 0.29) and mechanical complications (p = 0.84) between central venous catheters and peripherally inserted central venous catheters. CONCLUSIONS: In a PICU, peripherally inserted central venous catheters had lower occurrence of central line-associated bloodstream infection than central venous catheters; however, similar catheter survival probabilities were observed between both catheters. A central catheter tip position for both catheters and ultrasound-guided insertion for peripherally inserted central venous catheters may help limit unplanned catheter removal due to catheter-associated complications.

Long-Axis In-Plane Approach Versus Short-Axis Out-of-Plane Approach for Ultrasound-Guided Central Venous Catheterization in Pediatric Patients: A Randomized Controlled Trial.

OBJECTIVES: The aim of this study was to compare the occurrence of posterior wall puncture between the long-axis in-plane and the short-axis out-of-plane approaches in a randomized controlled trial of pediatric patients who underwent cardiovascular surgery under general anesthesia. DESIGN: Prospective randomized controlled trial. SETTING: Operating room of Osaka Women's and Children's Hospital. PATIENTS: Pediatric patients less than 5 years old who underwent cardiovascular surgery. INTERVENTIONS: Ultrasound-guided central venous catheterization using the long-axis in-plane approach and short-axis out-of-plane approach. MEASUREMENTS AND MAIN RESULTS: The occurrence of posterior wall puncture was compared between the long-axis in-plane and short-axis out-of-plane approaches for ultrasound-guided central venous catheterization. Patients were randomly allocated to a long-axis group or a short-axis group and underwent ultrasound-guided central venous catheterization in the internal jugular vein using either the long-axis in-plane approach (long-axis group) or the short-axis out-of-plane approach (short-axis group). After exclusion, 97 patients were allocated to the long-axis (n = 49) or short-axis (n = 48) groups. Posterior wall puncture rates were 8.2% (4/49) and 39.6% (19/48) in the long-axis and short-axis groups, respectively (relative risk, 0.21; 95% CI, 0.076-0.56; p = 0.0003). First attempt success rates were 67.3% (33/49) and 64.6% (31/48) in the long-axis and short-axis groups, respectively (relative risk, 1.04; 95% CI, 0.78-1.39; p = 0.77). Overall success rates within 20 minutes were 93.9% (46/49) and 93.8% (45/48) in the long-axis and short-axis groups, respectively (relative risk, 0.99; 95% CI, 0.90-1.11; p = 0.98). CONCLUSIONS: The long-axis in-plane approach for ultrasound-guided central venous catheterization is a useful technique for avoiding posterior wall puncture in pediatric patients, compared with the short-axis out-of-plane approach.

Dynamic Needle Tip Positioning for Ultrasound-Guided Placement of a Peripherally Inserted Central Catheter in Pediatric Patients.

OBJECTIVE: Although a few studies have reported the efficacy of ultrasound-guided peripherally inserted central catheter placement for pediatric patients, the procedure still is challenging. Ultrasound-guided dynamic needle tip positioning technique is useful for vascular catheterization. There have been no reports on using dynamic needle tip positioning for peripherally inserted central catheter placement. The authors assessed the rate of successful peripherally inserted central catheter placement with dynamic needle tip positioning. DESIGN: Case series. SETTING: Single tertiary institution. PARTICIPANTS: Forty patients <5 years old who were admitted to the pediatric intensive care unit after cardiac surgeries and required peripherally inserted central catheter placement. INTERVENTIONS: Peripherally inserted central catheter placement was performed under ultrasound guidance with dynamic needle tip positioning. The authors recorded the first attempt and overall success rates of peripherally inserted central catheter and outer cannula placement, time needed for outer cannula and peripherally inserted central catheter placement, and number of attempts. MEASUREMENTS AND MAIN RESULTS: The first attempt and overall success rates of peripherally inserted central catheter placement were 85% (n = 34) and 97.5% (n = 39), respectively. The first attempt and overall success rates of outer cannula placement were 87.5% (n = 35) and 100% (n = 40), respectively. Time needed for outer cannula placement was 59.5 (interquartile range 40.5-80.5) seconds and for peripherally inserted central catheter placement was 112.5 (interquartile range 91.5-159.5) seconds. The number of attempts was 1 (interquartile range 1-1 [range 1-5]). CONCLUSIONS: In pediatric patients, ultrasound-guided peripherally inserted central catheter placement using dynamic needle tip positioning attained a high success rate.

Ultrasonographic Detection of Micro-Bubbles in the Right Atrium to Confirm Peripheral Venous Catheter Position in Children.

OBJECTIVES: In pediatric patients, indwelling peripheral venous catheters are sometimes displaced to extravascular positions, causing infiltration or extravasation. No reliable techniques are available to confirm accurate IV catheterization. However, ultrasonographic detection of micro-bubble turbulence in the right atrium after saline injection has been reported to be useful in confirming central venous catheter positions in both adults and children. This study evaluated whether this micro-bubble detection test can offer better confirmation of peripheral venous catheter positions compared with the smooth saline injection technique in pediatric patients. DESIGN: Randomized controlled study. SETTING: Single tertiary PICU. PATIENTS: Pediatric patients (weighing < 15 kg) who already had or required a peripheral venous catheter. INTERVENTIONS: Patients were randomly allocated to either of the two groups (150 patients per group): undergoing either the micro-bubble detection test (M group) or the smooth saline injection test (S group). MEASUREMENTS AND MAIN RESULTS: The peripheral venous catheters were confirmed to be IV located in the final position in 137 and 139 patients in the M and S groups, respectively. In properly located catheters, the tests were positive in 100% (n = 137/137; sensitivity, 100%; 95% CI, 97.8-100), and in 89% (n = 124/139; 95% CI, 82.8-93.8) of the M and S groups, respectively (p = 0.0001). Among the catheters located in extravascular positions, the tests were negative in 100% (n = 13/13; specificity, 100%; 95% CI, 79.4-100), and in 64% (n = 7/11; 95% CI, 30.8-89.1) of the M and S groups, respectively (p = 0.017). CONCLUSIONS: The micro-bubble detection test is a useful technique for detecting extravasation and confirming proper positioning of peripheral IV catheters in pediatric patients.