Serum Urate-Lowering Efficacy and Safety of Tigulixostat in Gout Patients With Hyperuricemia: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Trial.

OBJECTIVE: To evaluate the safety and efficacy of the nonpurine xanthine oxidase inhibitor tigulixostat for lowering serum urate level in gout patients with hyperuricemia. METHODS: We conducted a multicenter, phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-finding trial. After screening, gout patients with hyperuricemia were randomly assigned, after appropriate washout, to receive daily oral administration of 50 mg, 100 mg, or 200 mg of tigulixostat, or placebo for 12 weeks. Colchicine gout flare prophylaxis was administered to all patients. The primary end point was the proportion of patients with a serum urate level <5.0 mg/dl at week 12. RESULTS: A total of 143 patients were randomized to receive tigulixostat 50 mg (n = 34), 100 mg (n = 38), or 200 mg (n = 37), or placebo (n = 34). A significantly greater proportion of patients in the tigulixostat groups achieved the target serum urate level <5.0 mg/dl at week 12 (47.1% in the 50 mg group, 44.7% in the 100 mg group, and 62.2% in the 200 mg group) compared to the placebo group (2.9%) (P < 0.0001). The mean percentage change in serum urate level from baseline was also significantly greater in the tigulixostat groups (-38.8% to -61.8%) than in the placebo group at all time points (P < 0.0001). The rate of gout flares requiring rescue treatment ranged from 9.4% to 13.2% in the tigulixostat and placebo groups. The incidence of adverse events was 50.0% to 56.8% across all groups, and their severity was mild or moderate. CONCLUSION: Tigulixostat significantly lowered serum urate compared to placebo at all doses studied with an acceptable safety profile.

Rapid discovery and classification of inhibitors of coronavirus infection by pseudovirus screen and amplified luminescence proximity homogeneous assay.

To identify potent antiviral compounds, we introduced a high-throughput screen platform that can rapidly classify hit compounds according to their target. In our platform, we performed a compound screen using a lentivirus-based pseudovirus presenting a spike protein of coronavirus, and we evaluated the hit compounds using an amplified luminescence proximity homogeneous assay (alpha) test with purified host receptor protein and the receptor binding domain of the viral spike. With our screen platform, we were able to identify both spike-specific compounds (class I) and broad-spectrum antiviral compounds (class II). Among the hit compounds, thiosemicarbazide was identified to be selective to the interaction between the viral spike and its host cell receptor, and we further optimized the binding potency of thiosemicarbazide through modification of the pyridine group. Among the class II compounds, we found raloxifene and amiodarone to be highly potent against human coronaviruses including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2. In particular, using analogs of the benzothiophene moiety, which is also present in raloxifene, we have identified benzothiophene as a novel structural scaffold for broad-spectrum antivirals. This work highlights the strong utility of our screen platform using a pseudovirus assay and an alpha test for rapid identification of potential antiviral compounds and their mechanism of action, which can lead to the accelerated development of therapeutics against newly emerging viral infections.

A Novel Propofol Dosing Regimen for Pediatric Sedation during Radiologic Tests.

The dose of propofol for pediatric sedation during radiologic tests has been proposed as an equation of 0.75 + 0.14 × age (months) + 45.82 × body surface area (m2) based on results in a previous study. We compared this equation and the conventional dosing strategy for sedation in children undergoing radiologic tests. An amount of 180 children scheduled for magnetic resonance imaging (MRI) were randomized to experimental and control groups. The initial induction dose of propofol calculated using the equation was administered in the experimental group. In the control group, children received 1 mg/kg of the initial induction dose of propofol. Then, 0.5 mg/kg of the additional dose was followed to induce sedation in both groups. When awake or moving, a rescue injection of 0.5 mg/kg propofol was given. The total induction dose was more significant in the experimental group. The number of injections for induction in the experimental group was lesser. The dose and number of rescue injections in the experimental group were significantly less. The equation for the induction dose of propofol in a previous study could achieve quick induction of sedation and prevent a rescue injection during sedation. However, caution is needed when using the equation.

The adjuvanted recombinant zoster vaccine co-administered with the 13-valent pneumococcal conjugate vaccine in adults aged ≥50 years: A randomized trial.

BACKGROUND: Herpes zoster (HZ) results from reactivation of latent varicella-zoster virus. Adults at increased risk of HZ (due to immunocompromising conditions or older age) are also at risk of pneumococcal disease, both of which are preventable by vaccination. We evaluated simultaneous versus sequential administration of the adjuvanted recombinant zoster vaccine (RZV) and the 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥50 years. METHODS: In this phase IIIB multinational trial (NCT03439657), participants were randomized 1:1 to receive either the first RZV dose and PCV13 simultaneously followed by the second RZV dose two months later (Co-Ad, N = 449), or at two-month intervals, PCV13, the first RZV dose, and the second RZV dose sequentially (Control, N = 463). Objectives were to demonstrate that immune responses to both vaccines are non-inferior when co-administered compared to sequential administration and to evaluate the safety of their co-administration. RESULTS: The RZV vaccine response rate (VRR) in the Co-Ad group was 99.1% (95% confidence interval [CI]: 97.6-99.7), meeting the VRR success criterion. Non-inferiority criteria for the Co-Ad versus Control group were also met for anti-glycoprotein E antibodies (adjusted geometric mean concentration Control/Co-Ad ratio 1.07 [95%CI: 0.99-1.16]) and all PCV13 serotypes (adjusted antibody geometric mean titer Control/Co-Ad ratios 1.02 [95%CI: 0.86-1.22] to 1.36 [95%CI: 1.07-1.73]). Upon co-administration, the frequency of solicited local adverse events was consistent with the known safety profile of each individual vaccine, whereas solicited general adverse events were within the same range as for RZV alone. CONCLUSIONS: RZV co-administered with PCV13 had an acceptable safety profile. Humoral immune responses to both vaccines were non-inferior when co-administered compared to sequential administration. These results suggest that adults may benefit from receiving RZV and a PCV at the same healthcare visit.

Deep Learning-Based Concrete Surface Damage Monitoring Method Using Structured Lights and Depth Camera.

Due to the increase in aging structures and the decrease in construction workforce, there is an increasing interest in automating structural damage monitoring. Surface damage on concrete structures, such as cracks, delamination, and rebar exposure, is one of the important parameters that can be used to estimate the condition of the structure. In this paper, deep learning-based detection and quantification of structural damage using structured lights and a depth camera is proposed. The proposed monitoring system is composed of four lasers and a depth camera. The lasers are projected on the surface of the structures, and the camera captures images of the structures while measuring distance. By calculating an image homography, the captured images are calibrated when the structure and sensing system are not in parallel. The Faster RCNN (Region-based Convolutional Neural Network) with Inception Resnet v2 architecture is used to detect three types of surface damage: (i) cracks; (ii) delamination; and (iii) rebar exposure. The detected damage is quantified by calculating the positions of the projected laser beams with the measured distance. The experimental results show that structural damage was detected with an F1 score of 0.83 and a median value of the quantified relative error of less than 5%.

Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19.

Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6, representing effective drugs. The time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs which acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI > 100), atovaquone, an anti-malarial (TI > 34), and ciclesonide, an inhalable corticosteroid (TI > 6). Furthermore, utilizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we tested combinations of remdesivir with selected drugs in Vero-E6 and Calu-3 cells, in lung organoids, and identified ciclesonide, nelfinavir, and camostat to be at least additive in vitro. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses.

Neutralization of Zika virus by E protein domain III-Specific human monoclonal antibody.

Zika virus (ZIKV) infection in both infants and adults is associated with neurological complications including, but not limited to, microcephaly and Guillain-Barre syndrome. Antibody therapy can be effective against virus infection. We isolated ZIKV envelope domain III-specific neutralizing antibodies (nAbs) from two convalescent patients with ZIKV infection. One antibody, 2F-8, exhibited potent in vitro neutralizing activity against Asian and American strains of ZIKV. To prevent FcγR-mediated antibody-dependent enhancement, we prepared IgG1 with LALA variation. A single dose of 2F-8 in the context of IgG1 or IgG1-LALA prior to or post lethal ZIKV challenge conferred complete protection in mice.

Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody.

Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe aggravating respiratory failure in infected patients, frequently resulting in mechanical ventilation. As limited therapeutic antibody is accumulated in lung tissue following systemic administration, inhalation is newly recognized as an alternative, possibly better, route of therapeutic antibody for pulmonary diseases. The nebulization process, however, generates diverse physiological stresses, and thus, the therapeutic antibody must be resistant to these stresses, remain stable, and form minimal aggregates. We first isolated a MERS-CoV neutralizing antibody that is reactive to the receptor-binding domain (RBD) of spike (S) glycoprotein. To increase stability, we introduced mutations into the complementarity-determining regions (CDRs) of the antibody. In the HCDRs (excluding HCDR3) in this clone, two hydrophobic residues were replaced with Glu, two residues were replaced with Asp, and four residues were replaced with positively charged amino acids. In LCDRs, only two Leu residues were replaced with Val. These modifications successfully generated a clone with significantly greater stability and equivalent reactivity and neutralizing activity following nebulization compared to the original clone. In summary, we generated a MERS-CoV neutralizing human antibody that is reactive to recombinant MERS-CoV S RBD protein for delivery via a pulmonary route by introducing stabilizing mutations into five CDRs.

An anti-Gn glycoprotein antibody from a convalescent patient potently inhibits the infection of severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a high fatality rate. Currently, no specific vaccine or treatment has been approved for this disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-displayed antibody library that was constructed from a patient who recovered from SFTS virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a conformational alteration that is critical for cell membrane fusion between the virus and host cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 247 of 272 SFTSV isolates previously reported. Together, these data suggest that Ab10 has potential to be developed into a therapeutic agent that could protect against more than 90% of reported SFTSV isolates.

High-throughput drug screening using the Ebola virus transcription- and replication-competent virus-like particle system.

The massive epidemic of Ebola virus disease (EVD) in West Africa, followed in recent months by two outbreaks in the Democratic Republic of the Congo, underline the importance of this severe disease. Because Ebola virus (EBOV) must be manipulated under biosafety level 4 (BSL4) containment, the discovery and development of virus-specific therapies have been hampered. Recently, a transient transfection-based transcription- and replication competent virus-like particle (trVLP) system was described, enabling modeling of the entire EBOV life cycle under BSL2 conditions. Using this system, we optimized the condition for bulk co-transfection of multiple plasmids, developed a luciferase reporter-based assay in 384-well microtiter plates, and performed a high-throughput screening (HTS) campaign of an 8,354-compound collection consisting of U.S. Food & Drug Administration (FDA) -approved drugs, bioactives, kinase inhibitors, and natural products in duplicates. The HTS achieved a good signal-to-background ratio with a low percent coefficient of variation resulting in Z' = 0.7, and data points were reproducible with R2 = 0.89, indicative of a robust assay. After applying stringent hit selection criteria of ≥70% EBOV trVLP inhibition and ≥70% cell viability, 381 hits were selected targeting early, entry, and replication steps and 49 hits targeting late, maturation, and secretion steps in the viral life cycle. Of the total 430 hits, 220 were confirmed by dose-response analysis in the primary HTS assay. They were subsequently triaged by time-of-addition assays, then clustered and ranked according to their chemical structures, biological functions, therapeutic index, and maximum inhibition. Several novel drugs have been identified to very efficiently inhibit EBOV. Interestingly, most showed pharmacological activity in treatments for central nervous system-related diseases. We developed and screened an HTS assay using the novel EBOV trVLP system. Newly identified inhibitors are useful tools to study the poorly understood EBOV life cycle. In addition, they also provide opportunities to either repurpose FDA-approved drugs or develop novel viral interventions to combat EVD.

A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin.

The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Å) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA. m826 fully protects mice against lethal challenge with H7N9 virus through mechanisms likely involving antibody-dependent cell-mediated cytotoxicity. Interestingly, immunogenetic analysis indicates that m826 is a germline antibody, and m826-like sequences can be identified in H7N9-infected patients, healthy adults, and newborn babies. These m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a tool for exploring mechanisms of virus infection inhibition by antibodies.

Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins.

Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.

Influenza Virus Infection, Interferon Response, Viral Counter-Response, and Apoptosis.

Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral outbreaks, new treatments are urgently needed. Developing new virus control modalities requires better understanding of virus-host interactions. Here, we describe how IAV infection triggers cellular apoptosis and how this process can be exploited towards the development of new therapeutics, which might be more effective than the currently available anti-influenza drugs.

Double Plant Homeodomain Fingers 2 (DPF2) Promotes the Immune Escape of Influenza Virus by Suppressing Beta Interferon Production.

The high mutation rates of the influenza virus genome facilitate the generation of viral escape mutants, rendering vaccines and drugs against influenza virus-encoded targets potentially ineffective. Therefore, we identified host cell determinants dispensable for the host but crucial for virus replication, with the goal of preventing viral escape and finding effective antivirals. To identify these host factors, we screened 2,732 human genes using RNA interference and focused on one of the identified host factors, the double plant homeodomain fingers 2 (DPF2/REQ) gene, for this study. We found that knockdown of DPF2 in cells infected with influenza virus resulted in decreased expression of viral proteins and RNA. Furthermore, production of progeny virus was reduced by two logs in the multiple-cycle growth kinetics assay. We also found that DPF2 was involved in the replication of seasonal influenza A and B viruses. Because DPF2 plays a crucial role in the noncanonical NF-κB pathway, which negatively regulates type I interferon (IFN) induction, we examined the relationship between DPF2 and IFN responses during viral infection. The results showed that knockdown of DPF2 resulted in increased expression of IFN-ß and induced phosphorylation of STAT1 in infected cells. In addition, high levels of several cytokines/chemokines (interleukin-8 [IL-8], IP-10, and IL-6) and antiviral proteins (MxA and ISG56) were produced by DPF2 knockdown cells. In conclusion, we identified a novel host factor, DPF2, that is required for influenza virus to evade the host immune response and that may serve as a potential antiviral target.IMPORTANCE Influenza virus is responsible for seasonal epidemics and occasional pandemics and is an ongoing threat to public health worldwide. Influenza virus relies heavily on cellular factors to complete its life cycle. Here we identified a novel host factor, DPF2, which is involved in influenza virus infection. Our results showed that DPF2 plays a crucial role in the replication and propagation of influenza virus. DPF2 functions in the noncanonical NF-κB pathway, which negatively regulates type I IFN induction. Thus, we investigated the relationship between the IFN response and DPF2 in influenza virus infection. Upon influenza virus infection, DPF2 dysregulated IFN-ß induction and expression of cytokines/chemokines and antiviral proteins. This study provides evidence that influenza virus utilizes DPF2 to escape host innate immunity.

Acid phosphatase 2 (ACP2) is required for membrane fusion during influenza virus entry.

Influenza viruses exploit host factors to successfully replicate in infected cells. Using small interfering RNA (siRNA) technology, we identified six human genes required for influenza A virus (IAV) replication. Here we focused on the role of acid phosphatase 2 (ACP2), as its knockdown showed the greatest inhibition of IAV replication. In IAV-infected cells, depletion of ACP2 resulted in a significant reduction in the expression of viral proteins and mRNA, and led to the attenuation of virus multi-cycle growth. ACP2 knockdown also decreased replication of seasonal influenza A and B viruses and avian IAVs of the H7 subtype. Interestingly, ACP2 depletion had no effect on the replication of Ebola or hepatitis C virus. Because ACP2 is known to be a lysosomal acid phosphatase, we assessed the role of ACP2 in influenza virus entry. While neither binding of the viral particle to the cell surface nor endosomal acidification was affected in ACP2-depleted cells, fusion of the endosomal and viral membranes was impaired. As a result, downstream steps in viral entry were blocked, including nucleocapsid uncoating and nuclear import of viral ribonucleoproteins. Our results established ACP2 as a necessary host factor for regulating the fusion step of influenza virus entry.

A naturally truncated NS1 protein of influenza A virus impairs its interferon-antagonizing activity and thereby confers attenuation in vitro.

The non-structural protein of influenza A virus (NS1A protein) is a multifunctional protein that antagonizes host antiviral responses and contributes to efficient viral replication during infection. However, most of its functions have been elucidated by generating recombinant viruses expressing mutated NS1 proteins that do not exist in nature. Recently, the novel H3N8 A/Equine/Kyonggi/SA1/2011 (KG11) influenza virus was isolated in Korea from horses showing respiratory disease symptoms. KG11 virus contains a naturally truncated NS gene segment with the truncation in the NS1A coding region, resulting in truncation of the effector domain of the NS1A protein. Using this KG11 virus, we investigated the role of truncated NS1A protein in the virus life cycle and its effect on host immune responses were compared to the A/Equine/Miami/1/1963 H3N8 (MA63) virus, which encodes a full-length NS1A protein. The replication of KG11 virus was attenuated by 2 logs in multiple-cycle growth, and its plaque size was significantly smaller than that of the MA63 virus. To understand the attenuation of KG11 virus, we evaluated the level of activation in Akt and interferon regulatory factor 3 (IRF-3) pathways and measured the induction of downstream genes. Our results showed that the activation of Akt was reduced, whereas phosphorylation of IRF-3 was increased in cells infected with KG11 virus when compared to MA63-virus-infected cells. We also determined that the expression of antiviral and pro-inflammatory genes was significantly increased. Taken together, these results revealed that the KG11 virus expressing the naturally truncated NS1A protein impairs the inhibition of host antiviral responses, thereby resulting in the attenuation of viral replication.

Identification of pyrrolo[3,2-c]pyridin-4-amine compounds as a new class of entry inhibitors against influenza viruses in vitro.

Various influenza virus entry inhibitors are being developed as therapeutic antiviral agents in ongoing preparation for emerging influenza viruses, particularly those that may possess drug resistance to the current FDA-approved neuraminidase inhibitors. In this study, small molecules having the pyrrolopyridinamine (PPA), aminothiadiazole (ATD), dihydrofuropyridine carboxamide (HPC), or imidazopyridinamine (IPA) moiety were selected from a target-focused chemical library for their inhibitory activity against influenza A virus by high-throughput screening using the PR8GFP assay. Activity was evaluated by measuring changes the proportion of GFP-expressing cells as a reflection of influenza virus infection. Among them, PPA showed broad-spectrum activity against multiple influenza A viruses and influenza B virus. PPA was found to block the early stages of influenza virus infection using a time-of-addition assay. Using additional phenotypic assays that dissect the virus entry process, it appears that the antiviral activity of PPA against influenza virus can be attributed to interference of the post-fusion process: namely, virus uncoating and nuclear import of viral nucleoprotein complexes. Based on these results, PPA is an attractive chemical moiety that can be used to develop new antiviral drug candidates against influenza viruses.

Extensive Viable Middle East Respiratory Syndrome (MERS) Coronavirus Contamination in Air and Surrounding Environment in MERS Isolation Wards.

BACKGROUND: The largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) outside the Middle East occurred in South Korea in 2015 and resulted in 186 laboratory-confirmed infections, including 36 (19%) deaths. Some hospitals were considered epicenters of infection and voluntarily shut down most of their operations after nearly half of all transmissions occurred in hospital settings. However, the ways that MERS-CoV is transmitted in healthcare settings are not well defined. METHODS: We explored the possible contribution of contaminated hospital air and surfaces to MERS transmission by collecting air and swabbing environmental surfaces in 2 hospitals treating MERS-CoV patients. The samples were tested by viral culture with reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence assay (IFA) using MERS-CoV Spike antibody, and electron microscopy (EM). RESULTS: The presence of MERS-CoV was confirmed by RT-PCR of viral cultures of 4 of 7 air samples from 2 patients' rooms, 1 patient's restroom, and 1 common corridor. In addition, MERS-CoV was detected in 15 of 68 surface swabs by viral cultures. IFA on the cultures of the air and swab samples revealed the presence of MERS-CoV. EM images also revealed intact particles of MERS-CoV in viral cultures of the air and swab samples. CONCLUSIONS: These data provide experimental evidence for extensive viable MERS-CoV contamination of the air and surrounding materials in MERS outbreak units. Thus, our findings call for epidemiologic investigation of the possible scenarios for contact and airborne transmission, and raise concern regarding the adequacy of current infection control procedures.

The effect of electromagnetic guidance system on early learning curve of ultrasound for novices.

BACKGROUND: Electromagnetic guidance reveals needle alignment and position relative to the image plane on an ultrasound view. This study compared the early learning curves of novices performing ultrasound-guided needle placement with (n = 10) or without electromagnetic guidance (n = 10). METHODS: Participants performed 30 ultrasound-guided needle placements using an echogenic stick (0.3-cm diameter) as a target inside a phantom model; this early learning period was divided into sequential periods (P1: 1-5, P2: 6-10, P3: 11-15, P4: 16-20, P5: 21-25, P6: 26-30 attempts). RESULTS: Using an in-plane approach, the time required for needle placement in the EMG group was significantly shorter than that of the non-EMG group in P1, P2, P4, and P6 and the number of needle advances of the EMG group was significantly smaller than that of the non-EMG group in P1 and P2. Using an out-of-plane approaches, the time required for needle placement in the EMG group was significantly shorter than that of the non-EMG group in all periods, but the number of needle advances was similar between both groups in P1-P5. CONCLUSIONS: The electromagnetic guidance system may be beneficial when performing ultrasound guided peripheral nerve blocks or vascular cannulation in the early learning period, especially by inexperienced operators with reducing patient risk.