Prescription of Oral Antibiotics and its Appropriateness for Outpatients in a Tertiary-Care Hospital in Korea.

OBJECTIVES: Antimicrobial stewardship programs (ASPs) have gained prominence with increased awareness regarding the importance of appropriate antibiotic use. However, ASP implementation for outpatient antibiotic prescriptions is uncommon, particularly in South Korea. This study aimed to analyse the patterns and appropriateness of outpatient antibiotic prescriptions at a tertiary care hospital in Korea. METHODS: We analysed the patterns of oral antibiotic prescription from June 1, 2018 to May 31, 2023, at the outpatient department of Seoul National University Bundang Hospital. Appropriateness was assessed for prescriptions issued between May 15 and May 19, 2023. The assessment criteria included: indications for antibiotic use, antibiotic choice, duration, dose, and frequency. Pharmacists and infectious diseases specialists performed evaluations. RESULTS: A total of 7,282,407 outpatient visits were recorded within the 5-year duration. Of these, 243,967 (3.4%) were prescribed oral antibiotics. The frequency of antibiotic prescription was highest in dentistry, dermatology, and urology departments. The most commonly prescribed antibiotics were cephalosporins, penicillins, and sulphonamides. Of the 423 prescriptions evaluated, 289 (68.3%) and 134 (31.7%) were for treatment and prophylaxis, respectively. Inappropriate prescriptions were identified in 28.4% (82/289) and 70.9% (95/134) of the treatment and prophylaxis cases, respectively. The primary reason for inadequacy in both treatment and prophylaxis was inappropriate indications, accounting for 46.3% (38/82) of treatment prescriptions and 96.8% (92/95) of prophylaxis prescriptions. CONCLUSIONS: Antibiotics were administered in 3.4% of all outpatient visits, with 28.4% of treatment and 70.9% of prophylactic antibiotics prescribed inappropriately. Proactive and expansive ASP activities by pharmacists should be considered in outpatient settings.

Comparison of the risk of pneumothorax in COVID-19 and seasonal influenza.

Limited evidence exists regarding the link between coronavirus disease 2019 (COVID-19) and pneumothorax. Therefore, we aimed to evaluate the occurrence rate of pneumothorax in hospitalized patients with COVID-19 and compare the risk of pneumothorax between patients with COVID-19 and influenza. This retrospective cohort study used patient data from the National Health Insurance Service of South Korea. Patients diagnosed with COVID-19 (December 2019 to December 2021) and influenza (January 2019 to December 2021) who required hospitalization and respiratory support were included. We identified 46,460 patients with COVID-19 and 6,117 with influenza. The occurrence rate of pneumothorax was 0.74% in patients with COVID-19. In an inverse probability of treatment weighting matched cohort, the Cox proportional hazards regression model showed that COVID-19 was not associated with an increased risk of pneumothorax compared to influenza (hazard ratio, 1.22; 95% confidence interval, 0.75-1.99). However, the risk of pneumothorax associated with COVID-19 compared to influenza was significantly higher in patients without chronic lung disease than in those with (P for heterogeneity = 0.037). In conclusion, COVID-19, compared with influenza, is not associated with an increased risk of pneumothorax; however, it is associated with an increased risk in patients without chronic lung disease.

Synthesis and quality assessment of combined time-series and static medical data using a real-world time-series generative adversarial network.

This study addresses challenges related to privacy issues in utilizing medical data, particularly the protection of personal information. To overcome this obstacle, the research focuses on data synthesis using real-world time-series generative adversarial networks (RTSGAN). A total of 53,005 data were synthesized using the dataset of 15,799 patients with colorectal cancer. The results of the quantitative evaluation of the synthetic data's quality are as follows: the Hellinger distance ranged from 0 to 0.25; the train on synthetic, test on real (TSTR) and train on real, test on synthetic (TRTS) results showed an average area under the curve of 0.99 and 0.98; a propensity mean squared error was 0.223. The synthetic and real data were similar in the qualitative methods including t-SNE and histogram analyses. The application of synthetic data in predicting five-year survival in colorectal cancer patients demonstrates comparable performance to models based on real data. This study employs distance to closest records and membership inference test to assess potential privacy exposure, revealing minimal risk. This study demonstrated that it is feasible to synthesize medical data, including time-series data, using the RTSGAN, and the synthetic data can be evaluated to accurately reflect the characteristics of real data through quantitative and qualitative methods as well as by utilizing real-world artificial intelligence models.

A Development of a Sound Recognition-Based Cardiopulmonary Resuscitation Training System.

The objective of this study was to develop a sound recognition-based cardiopulmonary resuscitation (CPR) training system that is accessible, cost-effective, easy-to-maintain and provides accurate CPR feedback. Beep-CPR, a novel device with accordion squeakers that emit high-pitched sounds during compression, was developed. The sounds emitted by Beep-CPR were recorded using a smartphone, segmented into 2-second audio fragments, and then transformed into spectrograms. A total of 6,065 spectrograms were generated from approximately 40 minutes of audio data, which were then randomly split into training, validation, and test datasets. Each spectrogram was matched with the depth, rate, and release velocity of the compression measured at the same time interval by the ZOLL X Series monitor/defibrillator. Deep learning models utilizing spectrograms as input were trained using transfer learning based on EfficientNet to predict the depth (Depth model), rate (Rate model), and release velocity (Recoil model) of compressions. Results: The mean absolute error (MAE) for the Depth model was 0.30 cm (95% confidence interval [CI]: 0.27-0.33). The MAE of the Rate model was 3.6/min (95% CI: 3.2-3.9). For the Recoil model, the MAE was 2.3 cm/s (95% CI: 2.1-2.5). External validation of the models demonstrated acceptable performance across multiple conditions, including the utilization of a newly-manufactured device, a fatigued device, and evaluation in an environment with altered spatial dimensions. We have developed a novel sound recognition-based CPR training system, that accurately measures compression quality during training. Significance: Beep-CPR is a cost-effective and easy-to-maintain solution that can improve the efficacy of CPR training by facilitating decentralized at-home training with performance feedback.

Real-time assessment of relative mitochondrial ATP synthesis response against inhibiting and stimulating substrates (MitoRAISE).

BACKGROUND: Mitochondria are known to synthesize adenosine triphosphate (ATP) through oxidative phosphorylation. Understanding and accurately measuring mitochondrial ATP synthesis rate can provide insights into the functional status of mitochondria and how it contributes to overall cellular energy homeostasis. Traditional methods only estimate mitochondrial function by measuring ATP levels at a single point in time or through oxygen consumption rates. This study introduced the relative mitochondrial ATP synthesis response against inhibiting and stimulating substrates (MitoRAISE), designed to detect real-time changes in ATP levels as the cells respond to substrates. METHODS: The sensitivity and specificity of the MitoRAISE assay were verified under various conditions, including the isolation of mitochondria, variations in cell numbers, cells exhibiting mitochondrial damage, and heterogeneous mixtures. Using peripheral blood mononuclear cells (PBMCs), we analyzed MitoRAISE data from 19 patients with breast cancer and 23 healthy women. RESULTS: The parameters observed in the MitoRAISE data increased depending on the quantity of isolated mitochondria and cell count, whereas it remained unmeasured in mitochondrial-damaged cell lines. Basal ATP, rotenone response, malonate response, and mitochondrial DNA copy numbers were lower in PBMCs from patients with breast cancer than in those from healthy women. CONCLUSIONS: The MitoRAISE assay has demonstrated its sensitivity and specificity by measuring relative ATP synthesis rates under various conditions. We propose MitoRAISE assay as a potential tool for monitoring changes in the mitochondrial metabolic status associated with various diseases.

The epidemiology and outcomes of severe road traffic injury by road user type in Korea: A nationwide retrospective observational study.

OBJECTIVES: Road traffic injuries (RTIs) pose a significant public health burden, and more than half of these fatalities are attributed to vulnerable road users (VRUs). This study aimed to evaluate the epidemiology and outcomes of severe RTIs in Korea by focusing on different types of road users. METHODS: This is nationwide retrospective observational study. Using data from the Korean Nationwide Severe Trauma Registry, this study analyzed severe RTI cases from 2016 to 2020. The study included EMS-treated severe trauma patients, defining severe RTI as cases with an injury severity score (ISS) ≥16 or out-of-hospital cardiac arrest (OHCA). The main variable of interest was the road user type, classified as motor vehicle occupants (MVOs), pedestrians, motorcyclists, and bicyclists. Trends and injury characteristics by road user type were analyzed, and multivariate logistic regression was conducted to calculate the adjusted odds ratios (AORs) and 95 % confidence intervals (CIs) of road user type for in-hospital mortality. RESULTS: Of the 143,021 EMS-treated severe trauma cases, 24,464 were included in this study. Pedestrians represented the largest group (n = 8,782; 35.9 %). More than half of the patients died (n = 12,620, 51.6 %), and a high proportion of patients had OHCA (n = 10,048, 41.1 %). There was no significant change in the overall severe RTI numbers from 2016 to 2020, but a decrease in pedestrian cases and an increase in motorcyclist cases were noted (both p for trend<0.05). Low usage of safety devices was observed (28.2 % of motor vehicle occupants used seat belts, 35.9 % of motorcyclists used helmets, and 9.6 % of bicyclists used helmets). Head injuries were most common, particularly among bicyclists (77.0 %) and motorcyclists (69.8 %). Compared to motor vehicle occupants, pedestrians (AOR [95 % CI] 1.12 [1.04-1.20]) and others (AOR [95 % CI] 1.30 [1.02-1.65]) had higher odds of mortality, while motorcyclists (AOR [95 % CI] 0.64 [0.59-0.69]) and bicyclists (AOR [95 % CI] 0.68 [0.60-0.76]) had lower odds of mortality. CONCLUSION: We found varying trends and injury characteristics in severe RTIs according to road user type. Adapting prevention strategies for evolving road user patterns, with particular attention to increasing safety device usage and addressing the high mortality associated with severe RTIs are warranted.

The Microbiological Characteristics of Acinetobacter Baumannii Associated With Early Mortality in Patients With Bloodstream Infection.

Background: Despite rapid deaths resulting from Acinetobacter baumannii bacteremia, the clinical impact of the microbiological characteristics of A baumannii strains on early mortality (EM) is unclear. We aimed to identify the microbiological characteristics of A baumannii strains associated with EM. Methods: Clinical information and isolates from patients with A baumannii bacteremia from January 2015 to December 2021 were collected. EM was defined as death within 3 days of the initial positive blood culture, whereas late mortality meant death within 5-30 days. The microbiological characteristics of A baumannii were analyzed using multilocus sequence typing, polymerase chain reactions, and a Galleria mellonella in vivo infection model. Results: Among 130 patients, 69 (53.1%) died within 30 days and EM occurred in 38 (55.1% of 30-day deaths). Sequence type 191 (ST191) strain was more prevalent in patients with EM than in 30-day survivors (31.6% vs 6.6%). Regarding virulence genes, bfmS was more frequent (92.1% vs 47.5%), whereas bauA was less frequent (13.2% vs 52.5%) in patients with EM than in 30-day survivors. Higher clinical severity, pneumonia, and ST191 infection were identified as independent risk factors for EM. In the G mellonella infection model, ST191, bfmS+, and bauA- isolates showed higher virulence than non-ST191, bfmS-, and bauA+ isolates, respectively. Conclusions: ST191 and bfmS were more frequently found in the EM group. ST191 infection was also an independent risk factor for EM and highly virulent in the in vivo model. Tailored infection control measures based on these characteristics are necessary for A baumannii bacteremia management.

Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling.

BACKGROUND: Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. METHODS: This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. RESULTS: We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age. CONCLUSIONS: Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.

Implementation of the new acts on driving under the influence of alcohol and clinical outcomes for patients severely injured in road traffic crashes.

OBJECTIVE: Driving under the influence (DUI) of alcohol is a major risk factor for fatal road traffic injuries (RTIs) worldwide. This study aimed to investigate the relationship between the implementation of new acts on DUI of alcohol and the clinical outcomes of patients with severe RTIs in Korea. METHODS: This is a community-based cross-sectional study using a nationwide severe trauma registry in Korea. In 2018, 2 acts with the Yoon Chang-Ho Act (Yoon's Act) were passed to strengthen the punishment for drunk driving fatal RTIs (first Yoon's act) and lower the blood alcohol concentration limit to restrict driver's licenses (second Yoon's act). The first Yoon's act was implemented on December 18, 2018, and the second Yoon's act was implemented on June 25, 2019. The study periods were categorized as pre-Act-1, pre-Act-2, Act-1, and Act-2 according to the application of Yoon's Act, and the study outcome was in-hospital mortality. Multivariable logistic regression analysis was conducted to estimate the relationship of the new acts and in-hospital mortality. RESULTS: Among a total of 20,376 patients with severe RTIs and 7,928 patients (drivers) with RTIs (hereafter drivers), the in-hospital mortality rates were 20.8% and 17.0%, and alcohol-related RTIs accounted for 9.7% and 8.1%, respectively. Severe RTIs tended to increase with each period (25.5 cases/day, 24.5 cases/day, 26.8 cases/day, and 30.4 cases/day, P for trend <.01). In-hospital mortality significantly decreased during the Act-2 period compared to the pre-Act-2 period for all patients with severe RTIs (adjusted odds ratio = 0.54, 95% confidence interval 0.43-0.67) and drivers with RTIs (adjusted odds ratio = 0.50, 95% confidence interval 0.34-0.73). CONCLUSIONS: Implementation of the new acts on DUI of alcohol was associated with lower odds for in-hospital mortality for patients with severe RTIs. Further studies are needed to evaluate the long-term impact of the new acts on reducing alcohol-related RTIs.

Association Between Ambulance Station Case Volume and Clinical Outcomes in Moderate to Severe Trauma.

OBJECTIVES: The effect of the case volume of emergency medical services (EMS) on the clinical outcomes of trauma is uncertain. The purpose of this study was to evaluate the association between the case volume of an ambulance station and clinical outcomes in moderate to severe trauma patients. METHODS: Adult trauma patients with injury severity scores greater than 8 who were transported by the EMS between 2018 and 2019 were analyzed. The main exposure was the annual case volume of moderate to severe trauma at the ambulance station where the patient-transporting ambulance was based: low-volume (less than 60 cases), intermediate-volume (between 60 and 89 cases), and high-volume (equal or greater than 90 cases). The primary outcome was in-hospital mortality. Multilevel multivariable logistic regression analysis was conducted to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs), with the high-volume group used as the reference. RESULTS: In total, 21,498 trauma patients were analyzed. The high-volume group exhibited lower in-hospital mortality, 447 (9.0%), compared to 867 (14.1%) in the intermediate-volume group and 1,458 (14.1%) in the low-volume group. There were a significantly higher odds of in-hospital mortality: the low-volume group (AOR 95% CI: 1.20 (0.95-1.51)) and intermediate-volume group (AOR 95% CI: 1.29 (1.02-1.64)) when compared to the high-volume group. CONCLUSIONS: The case volume at an ambulance station is associated with in-hospital mortality in patients with moderate to severe trauma. These results should be considered when constructing an EMS system and education program for prehospital trauma care.

2023 Survey on User Experience of Artificial Intelligence Software in Radiology by the Korean Society of Radiology.

OBJECTIVE: In Korea, radiology has been positioned towards the early adoption of artificial intelligence-based software as medical devices (AI-SaMDs); however, little is known about the current usage, implementation, and future needs of AI-SaMDs. We surveyed the current trends and expectations for AI-SaMDs among members of the Korean Society of Radiology (KSR). MATERIALS AND METHODS: An anonymous and voluntary online survey was open to all KSR members between April 17 and May 15, 2023. The survey was focused on the experiences of using AI-SaMDs, patterns of usage, levels of satisfaction, and expectations regarding the use of AI-SaMDs, including the roles of the industry, government, and KSR regarding the clinical use of AI-SaMDs. RESULTS: Among the 370 respondents (response rate: 7.7% [370/4792]; 340 board-certified radiologists; 210 from academic institutions), 60.3% (223/370) had experience using AI-SaMDs. The two most common use-case of AI-SaMDs among the respondents were lesion detection (82.1%, 183/223), lesion diagnosis/classification (55.2%, 123/223), with the target imaging modalities being plain radiography (62.3%, 139/223), CT (42.6%, 95/223), mammography (29.1%, 65/223), and MRI (28.7%, 64/223). Most users were satisfied with AI-SaMDs (67.6% [115/170, for improvement of patient management] to 85.1% [189/222, for performance]). Regarding the expansion of clinical applications, most respondents expressed a preference for AI-SaMDs to assist in detection/diagnosis (77.0%, 285/370) and to perform automated measurement/quantification (63.5%, 235/370). Most respondents indicated that future development of AI-SaMDs should focus on improving practice efficiency (81.9%, 303/370) and quality (71.4%, 264/370). Overall, 91.9% of the respondents (340/370) agreed that there is a need for education or guidelines driven by the KSR regarding the use of AI-SaMDs. CONCLUSION: The penetration rate of AI-SaMDs in clinical practice and the corresponding satisfaction levels were high among members of the KSR. Most AI-SaMDs have been used for lesion detection, diagnosis, and classification. Most respondents requested KSR-driven education or guidelines on the use of AI-SaMDs.

Limited impact of bacterial virulence on early mortality risk factors in Acinetobacter baumannii bacteremia observed in a Galleria mellonella model.

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

Gastrointestinal tract perforation after radiofrequency ablation for hepatic tumor: Incidence and risk factors.

OBJECTIVE: We analyzed the incidence and mortality rate of gastrointestinal (GI) tract perforation after radiofrequency ablation (RFA) for hepatic tumors and assess its risk factors. METHODS: This retrospective cohort study included 4799 patients with malignant tumors who underwent RFA (n = 7206). Sixty-nine cases of thermal injury to the GI tract were identified via a search of the electronic medical record system using index terms and divided into two groups according to the thermal injury with (n = 8) or without (n = 61) GI tract perforation based on follow-up CT reports. The risk factors for GI tract perforation were identified via multivariable logistic regression analysis using clinical, technical, and follow-up CT findings. RESULTS: The incidence of thermal injury to the GI tract and GI tract perforation was 0.96 % (69/7206) and 0.11 % (8/7206), respectively. The type of adjacent GI tract and history of diabetes mellitus differed significantly between the two groups (p < 0.05). The index tumor being located around the small intestine was the only significant risk factor for GI tract perforation after ablation (Odds ratio, 22.69; 95 % confidence interval, 2.59-198.34; p = 0.005 [reference standard, stomach]). All perforations were not identified on CT images immediately after RFA. The median time to detection was 20 days (range, 3-41 days). Two patients (25 %, 2/8) died due to perforation-related complications. CONCLUSION: GI tract perforation after RFA for hepatic tumors is rare; however, it is associated with high mortality. Thus, careful follow-up is required after RFA if the index tumor is located around the small intestine.

Disparity in guideline adherence for prehospital care according to patient age in emergency medical service transport for moderate to severe trauma.

OBJECTIVES: The aim of this study was to investigate the association between patient age and guideline adherence for prehospital care in emergency medical services (EMS) for moderate to severe trauma. METHODS: This was a retrospective observational study that used a nationwide EMS-based trauma database from 2016 to 2019. Adult trauma patients whose injury severity score was greater than or equal to nine were screened, and those with cardiac arrest or without outcome data were excluded. The enrolled patients were categorized into four groups according to patient age: young (<45 years), middle-aged (45-64 years), old (65-84 years), and very old (>84 years). The primary outcome was guideline adherence, which was defined as following all prehospital care components: airway management for level of consciousness below verbal response, oxygen supply for pulse oximetry under 94 %, intravenous fluid administration for systolic blood pressure under 90 mmHg, scene resuscitation time within 10 min, and transport to the trauma center or level 1 emergency department. Multivariable logistic regression was conducted to calculate the adjusted odds ratios (aORs) and 95 % confidence intervals (95 % CIs). RESULTS: Among the 430,365 EMS-treated trauma patients, 38,580 patients were analyzed-9,573 (24.8 %) in the young group, 15,296 (39.7 %) in the middle-aged group, 9,562 (24.8 %) in the old group, and 4,149 (10.8 %) in the very old group. The main analysis revealed a lower probability of guideline adherence in the old group (aOR 95 % CI = 0.84 (0.76-0.94)) and very old group (aOR 95 % CI = 0.68 (0.58-0.81)) than in the young group. CONCLUSION: We found disparities in guideline adherence for prehospital care according to patient age at the time of EMS assessment of moderate to severe trauma. Considering this disparity, the prehospital trauma triage and management for older patients needs to be improved and educated to EMS providers.

Trends of antibiotic use at the end-of-life of cancer and non-cancer decedents: a nationwide population-based longitudinal study (2006-2018).

Objective: This study aimed to assess the actual burden of antibiotic use among end-of-life (EOL) patients in South Korea and to compare trends between cancer and non-cancer decedents. Design: Population-based mortality follow-back study. Setting: Data from the Korean National Health Insurance Database, covering the period from January1, 2006, to December 31, 2018, provided for research by the National Health Insurance Service (NHIS), were used. Participants: All decedents from 2006 to 2018 were included and categorized as cancer decedents or non-cancer decedents. Methods: Annual antibiotic consumption rates and prescription rates were calculated, and Poisson regression was used to estimate their trends. Results: Overall antibiotic consumption rates decreased slightly among decedents in their final month with a less pronounced annual decrease rate among cancer decedents compared to non-cancer decedents (0.4% vs 2.3% per year, P <.001). Over the study period, although narrow spectrum antibiotics were used less, utilization and prescription of broad-spectrum antibiotics steadily increased, and prescription rates were higher in cancer decedents compared to non-cancer controls. Specifically, carbapenem prescription rates increased from 5.6% to 18.5%, (RR 1.087, 95% CI 1.085-1.088, P <.001) in cancer decedents and from 2.9% to 13.2% (RR 1.115, 95% CI 1.113-1.116, P <.001) in non-cancer decedents. Conclusions: Our findings show that patients at the EOL, especially those with cancer, are increasingly and highly exposed to broad-spectrum antibiotics. Measures of antibiotic stewardship are required among this population.

Value of Sonazoid-enhanced ultrasonography in characterizing indeterminate focal liver lesions on gadoxetic acid-enhanced liver MRI in patients without risk factors for hepatocellular carcinoma.

PURPOSE: To evaluate the added value of contrast-enhanced ultrasonography (CEUS) using Sonazoid in characterizing focal liver lesions (FLLs) with indeterminate findings on gadoxetic acid-enhanced liver MRI in patients without risk factors for hepatocellular carcinoma (HCC). METHODS: Patients who underwent CEUS using Sonazoid for characterizing indeterminate FLLs on gadoxetic acid-enhanced liver MRI were. The indeterminate FLLs were classified according to the degree of malignancy on a 5-point scale on MRI and combined MRI and CEUS. The final diagnosis was made either pathologically or based on more than one-year follow-up. The diagnostic performance was assessed using a receiver operating characteristic (ROC) curve analysis, and the net reclassification improvement (NRI) was calculated. RESULTS: A total of 97 patients (mean age, 49 years ± 16, 41 men, 80 benign and 17 malignant lesions) were included. When CEUS was added to MRI, the area under the ROC curve increased, but the difference was not statistically significant (0.87 [95% confidence interval {CI}, 0.77-0.98] for MRI vs 0.93 [95% CI, 0.87-0.99] for CEUS added to MRI, P = 0.296). The overall NRI was 0.473 (95% CI, 0.100-0.845; P = 0.013): 33.8% (27/80) of benign lesions and 41.2% (7/17) of malignant lesions were appropriately reclassified, whereas 10.0% (8/80) of benign lesions and 17.6% (3/17) of malignant lesions were incorrectly reclassified. CONCLUSIONS: Although performing CEUS with Sonazoid did not significantly improve the overall diagnostic performance in characterizing indeterminate FLLs on gadoxetic acid-enhanced liver MRI in patients without risk factors for HCC, it may increase radiologist's confidence in classifying FLLs.

Computational insights into allosteric inhibition of focal adhesion kinase: A combined pharmacophore modeling and molecular dynamics approach.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that modulates integrin and growth factor signaling pathways and is implicated in cancer cell migration, proliferation, and survival. Over the past decade various, FAK kinase, FERM, and FAT domain inhibitors have been reported and a few kinase domain inhibitors are under clinical consideration. However, few of them were identified as multikinase inhibitors. In kinase drug design selectivity is always a point of concern, to improve selectivity allosteric inhibitor development is the best choice. The current research utilized a pharmacophore modeling (PM) approach to identify novel allosteric inhibitors of FAK. The all-available allosteric inhibitor bound 3D structures with PDB ids 4EBV, 4EBW, and 4I4F were utilized for the pharmacophore modeling. The validated PM models were utilized to map a database of 770,550 compounds prepared from ZINC, EXIMED, SPECS, ASINEX, and InterBioScreen, aiming to identify potential allosteric inhibitors. The obtained compounds from screening step were forwarded to molecular docking (MD) for the prediction of binding orientation inside the allosteric site and the results were evaluated with the known FAK allosteric inhibitor (REF). Finally, 14 FAK-inhibitor complexes were selected from the docking study and were studied under molecular dynamics simulations (MDS) for 500 ns. The complexes were ranked according to binding free energy (BFE) and those demonstrated higher affinity for allosteric site of FAK than REF inhibitors were selected. The selected complexes were further analyzed for intermolecular interactions and finally, three potential allosteric inhibitor candidates for the inhibition of FAK protein were identified. We believe that identified scaffolds may help in drug development against FAK as an anticancer agent.

Persistent differences in the immunogenicity of the two COVID-19 primary vaccines series, modulated by booster mRNA vaccination and breakthrough infection.

INTRODUCTION: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear. METHODS: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike1) and beta and gamma variant (Spike2) were utilized. RESULTS: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike1 and Spike2 proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike2 response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05). CONCLUSION: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs.

Amoebicidal effect of chlorine dioxide gas against pathogenic Naegleria fowleri and Acanthamoeba polyphaga.

The pathogenic free-living amoebae, Naegleria fowleri and Acanthamoeba polyphaga, are found in freshwater, soil, and unchlorinated or minimally chlorinated swimming pools. N. fowleri and A. polyphaga are becoming problematic as water leisure activities and drinking water are sources of infection. Chlorine dioxide (ClO2) gas is a potent disinfectant that is relatively harmless to humans at the concentration used for disinfection. In this study, we examined the amoebicidal effects of ClO2 gas on N. fowleri and A. polyphaga. These amoebae were exposed to ClO2 gas from a ready-to-use product (0.36 ppmv/h) for 12, 24, 36, and 48 h. Microscopic examination showed that the viability of N. fowleri and A. polyphaga was effectively inhibited by treatment with ClO2 gas in a time-dependent manner. The growth of N. fowleri and A. polyphaga exposed to ClO2 gas for 36 h was completely inhibited. In both cases, the mRNA levels of their respective actin genes were significantly reduced following treatment with ClO2 gas. ClO2 gas has an amoebicidal effect on N. fowleri and A. polyphaga. Therefore, ClO2 gas has been proposed as an effective agent for the prevention and control of pathogenic free-living amoeba contamination.