Automatic segmentation of cardiac structures for breast cancer radiotherapy

Background and purpose We developed an automatic method to segment cardiac substructures given a radiotherapy planning CT images to support epidemiological studies or clinical trials looking at cardiac disease endpoints after radiotherapy. Material and methods We used a most-similar atlas selection algorithm and 3D deformation combined with 30 detailed cardiac atlases. We cross-validated our method within the atlas library by evaluating geometric comparison metrics and by comparing cardiac doses for simulated breast radiotherapy between manual and automatic contours. We analyzed the impact of the number of cardiac atlas in the library and the use of manual guide points on the performance of our method. Results The Dice Similarity Coefficients from the cross-validation reached up to 97% (whole heart) and 80% (chambers). The Average Surface Distance for the coronary arteries was less than 10.3 mm on average, with the best agreement (7.3 mm) in the left anterior descending artery (LAD). The dose comparison for simulated breast radiotherapy showed differences less than 0.06 Gy for the whole heart and atria, and 0.3 Gy for the ventricles. For the coronary arteries, the dose differences were 2.3 Gy (LAD) and 0.3 Gy (other arteries). The sensitivity analysis showed no notable improvement beyond ten atlases and the manual guide points does not significantly improve performance. Conclusion We developed an automated method to contour cardiac substructures for radiotherapy CTs. When combined with accurate dose calculation techniques, our method should be useful for cardiac dose reconstruction of a large number of patients in epidemiological studies or clinical trials

First Successful Application of Preimplantation Genetic Diagnosis for Lethal Neonatal Rigidity and Multifocal Seizure Syndrome in Korea: A Case Report

Lethal neonatal rigidity and multifocal seizure syndrome (RMFSL) is a severe autosomal recessive epileptic encephalopathy characterized by rigidity, intractable multifocal seizures, microcephaly, apnea, and bradycardia immediately after birth. RMFSL is related to a mutation in breast cancer 1-associated ataxia telangiectasia mutated activation-1 protein (BRAT1). We report a case of a female infant born to non-consanguineous Korean parents who developed hypertonia, dysmorphic features, progressive encephalopathy with refractory seizures at birth, and worsening intermittent apnea, leading to intubation and death at 137 days of age. The initial repeated electroencephalographic findings were normal; however, a pattern of focal seizures emerged at 35 days of life. Rapid trio whole-exome sequencing revealed heterozygous mutations c.1313_1314delAG p.(Gln438Argfs*51) and c.1276C>T p. (Gln426*) in BRAT1. After genetic counseling for pregnancy planning, a preimplantation genetic diagnosis for targeted BRAT1 mutations was successfully performed, and a healthy baby was born. To our knowledge, this is the first reported case of a Korean patient with compound heterozygous mutations in BRAT1. An early and accurate genetic diagnosis can help provide timely treatment to patients and indicate the need for reproductive counseling for parents for family planning

Application of an Automatic Segmentation Method for Evaluating Cardiac Structure Doses Received by Breast Radiotherapy Patients

BACKGROUND AND PURPOSE: Quantifying radiation dose to cardiac substructures is important for research on the etiology and prevention of complications following radiotherapy; however, segmentation of substructures is challenging. In this study we demonstrate the application of our atlas-based automatic segmentation method to breast cancer radiotherapy plans for generating radiation doses in support of late effects research. MATERIAL AND METHODS: We applied our segmentation method to contour heart substructures on the computed tomography (CT) images of 70 breast cancer patients who received external photon radiotherapy. Two cardiologists provided manual segmentation of the whole heart (WH), left/right atria, left/right ventricles, and left anterior descending artery (LAD). The automatically contours were compared with manual delineations to evaluate similarity in terms of geometry and dose. RESULTS: The mean Dice similarity coefficient between manual and automatic segmentations was 0.96 for the WH, 0.65 to 0.82 for the atria and ventricles, and 0.06 for the LAD. The mean average surface distance was 1.2 mm for the WH, 3.4 to 4.1 mm for the atria and ventricles, and 6.4 mm for the LAD. We found the dose to the cardiac substructures based on our automatic segmentation agrees with manual segmentation within expected observer variability. For left breast patients, the mean absolute difference in mean dose was 0.1 Gy for the WH, 0.2 to 0.7 Gy for the atria and ventricles, and 1.8 Gy for the LAD. For right breast patients, these values were 0.0 Gy, 0.1 to 0.4 Gy, and 0.4 Gy, respectively. CONCLUSION: Our automatic segmentation method will facilitate the development of radiotherapy prescriptive criteria for mitigating cardiovascular complications

Comparison of Ertapenem and Ceftriaxone Therapy for Acute Pyelonephritis and Other Complicated Urinary Tract Infections in Korean Adults: A Randomized, Double-Blind, Multicenter Trial

The efficacy and safety of ertapenem, 1 g once daily, were compared with that of ceftriaxone, 2 g once daily, for the treatment of adults with acute pyelonephritis (APN) and complicated urinary tract infections (cUTIs) in a prospective, multicenter, double-blinded, randomized study. After ≥ 3 days of parenteral study therapy, patients could be switched to an oral agent. Of 271 patients who were initially stratified by APN (n = 210) or other cUTIs (n = 61), 66 (48.9%) in the ertapenem group and 71 (52.2%) in the ceftriaxone group were microbiologically evaluable. The mean duration of parenteral and total therapy, respectively, was 5.6 and 13.8 days for ertapenem and 5.8 and 13.8 days for ceftriaxone. The most common pathogen was Escherichia coli. At the primary efficacy endpoint 5-9 days after treatment, 58 (87.9%) patients in the ertapenem group and 63 (88.7%) in the ceftriaxone had a favorable microbiological response. When compared by stratum and severity, the outcomes in the two groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. The results indicate that ertapenem is highly effective and safe for the treatment of APN and cUTIs

Bloodstream Infections and Clinical Significance of Healthcare-associated Bacteremia: A Multicenter Surveillance Study in Korean Hospitals

Recent changes in healthcare systems have changed the epidemiologic paradigms in many infectious fields including bloodstream infection (BSI). We compared clinical characteristics of community-acquired (CA), hospital-acquired (HA), and healthcare-associated (HCA) BSI. We performed a prospective nationwide multicenter surveillance study from 9 university hospitals in Korea. Total 1,605 blood isolates were collected from 2006 to 2007, and 1,144 isolates were considered true pathogens. HA-BSI accounted for 48.8%, CA-BSI for 33.2%, and HCA-BSI for 18.0%. HA-BSI and HCA-BSI were more likely to have severe comorbidities. Escherichia coli was the most common isolate in CA-BSI (47.1%) and HCA-BSI (27.2%). In contrast, Staphylococcus aureus (15.2%), coagulase-negative Staphylococcus (15.1%) were the common isolates in HA-BSI. The rate of appropriate empiric antimicrobial therapy was the highest in CA-BSI (89.0%) followed by HCA-BSI (76.4%), and HA-BSI (75.0%). The 30-day mortality rate was the highest in HA-BSI (23.0%) followed by HCA-BSI (18.4%), and CA-BSI (10.2%). High Pitt score and inappropriate empirical antibiotic therapy were the independent risk factors for mortality by multivariate analysis. In conclusion, the present data suggest that clinical features, outcome, and microbiologic features of causative pathogens vary by origin of BSI. Especially, HCA-BSI shows unique clinical characteristics, which should be considered a distinct category for more appropriate antibiotic treatment

Laboratory information management system for COVID-19 non-clinical efficacy trial data

Background : As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results : In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions : This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.This research was supported by the National research foundation of Korea(NRF) grant funded by the Korea government(MSIT) (2020M3A9I2109027 and 2021M3H9A1030260)

Transformation Products of Emerging Pollutants Explored Using Non-Target Screening: Perspective in the Transformation Pathway and Toxicity Mechanism—A Review

The scientific community has increasingly focused on forming transformation products (TPs) from environmental organic pollutants. However, there is still a lot of discussion over how these TPs are generated and how harmful they are to living terrestrial or aquatic organisms. Potential transformation pathways, TP toxicity, and their mechanisms require more investigation. Non-target screening (NTS) via high-resolution mass spectrometry (HRMS) in model organisms to identify TPs and the formation mechanism on various organisms is the focus of this review. Furthermore, uptake, accumulation process, and potential toxicity with their detrimental consequences are summarized in various organisms. Finally, challenges and future research initiatives, such as performing NTS in a model organism, characterizing and quantifying TPs, and evaluating future toxicity studies on TPs, are also included in this review

New skeletal dose coefficients of the ICRP-110 reference phantoms for idealized external fields to photons and neutrons using dose response functions (DRFs)

The International Commission on Radiological Protection (ICRP) Publication 116 was released to provide a comprehensive dataset of the dose coefficients (DCs) for external exposures produced with the adult reference voxel phantoms of ICRP Publication 110. Although an advanced skeletal dosimetry method for photons and neutrons using fluence-to-dose response functions (DRFs) was introduced in ICRP Publication 116, the ICRP-116 skeletal DCs were calculated by using the simple method conventionally used (i.e., doses to red bone marrow and endosteum approximated by doses to spongiosa and/or medullary cavities). In the present study, the photon and neutron DRFs were used to produce skeletal DCs of the ICRP-110 reference phantoms, which were then compared with the ICRP-116 DCs. For photons, there were significant differences by up to ∼2.8 times especially at energies <0.3 MeV. For neutrons, the differences were generally small over the entire energy region (mostly <20%). The general impact of the DRF-based skeletal DCs on the effective dose calculations was negligibly small, supporting the validity of the ICRP-116 effective DCs despite their skeletal DCs derived from the simple method. Meanwhile, we believe that the DRF-based skeletal DCs could be beneficial in better estimates of skeletal doses of individuals for risk assessments

Implications of using a 50-μm-thick skin target layer in skin dose coefficient calculation for photons, protons, and helium ions

In a previous study, a set of polygon-mesh (PM)-based skin models including a 50-μm-thick radiosensitive target layer were constructed and used to calculate skin dose coefficients (DCs) for idealized external beams of electrons. The results showed that the calculated skin DCs were significantly different from the International Commission on Radiological Protection (ICRP) Publication 116 skin DCs calculated using voxel-type ICRP reference phantoms that do not include the thin target layer. The difference was as large as 7,700 times for electron energies less than 1 MeV, which raises a significant issue that should be addressed subsequently. In the present study, therefore, as an extension of the initial, previous study, skin DCs for three other particles (photons, protons, and helium ions) were calculated by using the PM-based skin models and the calculated values were compared with the ICRP-116 skin DCs. The analysis of our results showed that for the photon exposures, the calculated values were generally in good agreement with the ICRP-116 values. For the charged particles, by contrast, there was a significant difference between the PM-model-calculated skin DCs and the ICRP-116 values. Specifically, the ICRP-116 skin DCs were smaller than those calculated by the PM models—which is to say that they were underestimated—by up to ∼16 times for both protons and helium ions. These differences in skin dose also significantly affected the calculation of the effective dose (E) values, which is reasonable, considering that the skin dose is the major factor determining effective dose calculation for charged particles. The results of the current study generally show that the ICRP-116 DCs for skin dose and effective dose are not reliable for charged particles

Susceptibility to SARS-CoV-2 and MERS-CoV in Beagle Dogs

The coronavirus disease 19 (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), has resulted in unprecedented challenges to healthcare worldwide. In particular, the anthroponotic transmission of human coronaviruses has become a common concern among pet owners. Here, we experimentally inoculated beagle dogs with SARS-CoV-2 or Middle East respiratory syndrome (MERS-CoV) to compare their susceptibility to and the pathogenicity of these viruses. The dogs in this study exhibited weight loss and increased body temperatures and shed the viruses in their nasal secretions, feces, and urine. Pathologic changes were observed in the lungs of the dogs inoculated with SARS-CoV-2 or MERS-CoV. Additionally, clinical characteristics of SARS-CoV-2, such as increased lactate dehydrogenase levels, were identified in the current study