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Background@#To propose a deep learning architecture for automatically detecting the complex structure of the aortic annulus plane using cardiac computed tomography (CT) for transcatheter aortic valve replacement (TAVR). @*Methods@#This study retrospectively reviewed consecutive patients who underwent TAVR between January 2017 and July 2020 at a tertiary medical center. Annulus Detection Permuted AdaIN network (ADPANet) based on a three-dimensional (3D) U-net architecture was developed to detect and localize the aortic annulus plane using cardiac CT. Patients (N = 72) who underwent TAVR between January 2017 and July 2020 at a tertiary medical center were enrolled. Ground truth using a limited dataset was delineated manually by three cardiac radiologists. Training, tuning, and testing sets (70:10:20) were used to build the deep learning model. The performance of ADPANet for detecting the aortic annulus plane was analyzed using the root mean square error (RMSE) and dice similarity coefficient (DSC). @*Results@#In this study, the total dataset consisted of 72 selected scans from patients who underwent TAVR. The RMSE and DSC values for the aortic annulus plane using ADPANet were 55.078 ± 35.794 and 0.496 ± 0.217, respectively. @*Conclusion@#Our deep learning framework was feasible to detect the 3D complex structure of the aortic annulus plane using cardiac CT for TAVR. The performance of our algorithms was higher than other convolutional neural networks.
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Background@#In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. @*Methods@#The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. @*Results@#An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3–4 months. @*Conclusion@#We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media.Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.
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Objective@#This study aimed to evaluate the effect of implementing the consensus statement from the Asian Society of Cardiovascular Imaging-Practical Tutorial 2020 (ASCI-PT 2020) on the reliability of cardiac MR with late gadolinium enhancement (CMR-LGE) myocardial viability scoring between observers in the context of ischemic cardiomyopathy. @*Materials and Methods@#A total of 17 cardiovascular imaging experts from five different countries evaluated CMR obtained in 26 patients (male:female, 23:3; median age [interquartile range], 55.5 years [50–61.8]) with ischemic cardiomyopathy. For LGE scoring, based on the 17 segments, the extent of LGE in each segment was graded using a five-point scoring system ranging from 0 to 4 before and after exposure according to the consensus statement. All scoring was performed via webbased review. Scores for slices, vascular territories, and total scores were obtained as the sum of the relevant segmental scores. Interobserver reliability for segment scores was assessed using Fleiss’ kappa, while the intraclass correlation coefficient (ICC) was used for slice score, vascular territory score, and total score. Inter-observer agreement was assessed using the limits of agreement from the mean (LoA). @*Results@#Interobserver reliability (Fleiss’ kappa) in each segment ranged 0.242–0.662 before the consensus and increased to 0.301–0.774 after the consensus. The interobserver reliability (ICC) for each slice, each vascular territory, and total score increased after the consensus (slice, 0.728–0.805 and 0.849–0.884; vascular territory, 0.756–0.902 and 0.852–0.941; total score, 0.847 and 0.913, before and after implementing the consensus statement, respectively. Interobserver agreement in scoring also improved with the implementation of the consensus for all slices, vascular territories, and total score. The LoA for the total score narrowed from ± 10.36 points to ± 7.12 points. @*Conclusion@#The interobserver reliability and agreement for CMR-LGE scoring for ischemic cardiomyopathy improved when following guidance from the ASCI-PT 2020 consensus statement.
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To develop Korean coronavirus disease (COVID-19) chest imaging justification guidelines, eight key questions were selected and the following recommendations were made with the evidence-based clinical imaging guideline adaptation methodology. It is appropriate not to use chest imaging tests (chest radiograph or CT) for the diagnosis of COVID-19 in asymptomatic patients. If reverse transcription-polymerase chain reaction testing is not available or if results are delayed or are initially negative in the presence of symptoms suggestive of COVID-19, chest imaging tests may be considered. In addition to clinical evaluations and laboratory tests, chest imaging may be contemplated to determine hospital admission for asymptomatic or mildly symptomatic unhospitalized patients with confirmed COVID-19. In hospitalized patients with confirmed COVID-19, chest imaging may be advised to determine or modify treatment alternatives. CT angiography may be considered if hemoptysis or pulmonary embolism is clinically suspected in a patient with confirmed COVID-19. For COVID-19 patients with improved symptoms, chest imaging is not recommended to make decisions regarding hospital discharge. For patients with functional impairment after recovery from COVID-19, chest imaging may be considered to distinguish a potentially treatable disease.
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The association between lung injury and exposure to humidifier disinfectant (HD) containing a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) has been controversial in South Korea. This study conducts a literature review in order to evaluate the likelihood of CMIT/MIT reaching the lower part of the respiratory tract and causing lung injury. A literature review focused on the inhalation risk of HD containing a mixture of CMIT and MIT. The major contents included the physicochemical properties of CMIT and MIT contained in HDs and methodological reviews on substance analysis, toxicity tests and clinical cases. HD products marketed in South Korea have been reported to contain approximately 1–2% CMIT and 0.2–0.6% MIT along with magnesium nitrate (20–25%), magnesium chloride (0.2–1.0%), and water (70–75%). The types of CMIT and MIT dispersed into the air and deposited in the respiratory tract are assumed to be either gaseous substances or nanoparticles mixed with magnesium salts. The result of the literature review including clinical cases of lung injury among CMIT/MIT HD product users, demonstrated that these chemicals likely reach the lower respiratory tract and accordingly cause lung injury.A number of humidifier disinfectant-associated lung injury cases with clinical evidence should be prioritized in risk assessment of HD containing CMIT and MIT, even though there might be insufficient evidence in all related areas, including inhalation exposure assessment studies, animal testing, and epidemiological studies.
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Objective@#To assess the effect of left atrial appendage (LAA) isolation on LAA emptying and left atrial (LA) function using cardiac MRI in patients who underwent successful catheter ablation of atrial fibrillation (AF). @*Materials and Methods@#This retrospective study included 84 patients (mean age, 59 ± 10 years; 67 males) who underwent cardiac MRI after successful catheter ablation of AF. According to the electrical activity of LAA after catheter ablation, patients showed either LAA isolation or LAA normal activity. The LAA emptying phase (LAA-EP, in the systolic phase [SP] or diastolic phase), LAA emptying flux (LAA-EF, mL/s), and LA ejection fraction (LAEF, %) were evaluated by cardiac MRI. @*Results@#Of the 84 patients, 61 (73%) and 23 (27%) patients showed LAA normal activity and LAA isolation, respectively.Incidence of LAA emptying in SP was significantly higher in LAA isolation (91% vs. 0%, p < 0.001) than in LAA normal activation. LAA-EF was significantly lower in LAA isolation (40.1 ± 16.2 mL/s vs. 80.2 ± 25.1 mL/s, pp < 0.001) than in LAA normal activity. Furthermore, LAEF was significantly lower in LAA isolation (23.7% ± 11.2% vs. 31.1% ± 16.6%, p = 0.04) than in LAA normal activity. Multivariate analysis demonstrated that the LAA-EP was independent from LAEF (p = 0.01). @*Conclusion@#LAA emptying in SP may be a critical characteristic of LAA isolation, and it may adversely affect the LAEF after catheter ablation of AF.
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Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) characterized by an inhaled inciting antigen that leads to the inflammation of the lung parenchyma and small airway with immunologic reactions. Over the last decades, the most effective therapeutic option for HP has been limited to antigen avoidance. The differential diagnosis of HP from other ILDs is the beginning of treatment as well as diagnosis. However, the presence of several overlapping clinical and radiologic features makes differentiating HP from other ILDs particularly challenging. In 2020, a multidisciplinary committee of experts from the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax suggested a new clinical practice guideline classifying HP into nonfibrotic and fibrotic phenotypes on the basis of chest high-resolution CT (HRCT) findings. Therefore, we introduced a new diagnostic algorithm based on chest HRCT in the clinical practice guideline for the diagnosis of HP.
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Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) characterized by an inhaled inciting antigen that leads to the inflammation of the lung parenchyma and small airway with immunologic reactions. Over the last decades, the most effective therapeutic option for HP has been limited to antigen avoidance. The differential diagnosis of HP from other ILDs is the beginning of treatment as well as diagnosis. However, the presence of several overlapping clinical and radiologic features makes differentiating HP from other ILDs particularly challenging. In 2020, a multidisciplinary committee of experts from the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax suggested a new clinical practice guideline classifying HP into nonfibrotic and fibrotic phenotypes on the basis of chest high-resolution CT (HRCT) findings. Therefore, we introduced a new diagnostic algorithm based on chest HRCT in the clinical practice guideline for the diagnosis of HP.
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Purpose@#Painful muscle cramps are a common complication in liver cirrhosis patients, and no effective treatment is available.This pilot study aimed to evaluate whether taurine supplementation improves muscle cramps in Korean cirrhotic patients. @*Materials and Methods@#Ten cirrhotic patients who experienced muscle cramps one or more times/week were enrolled in this prospective single-arm study and administered with an oral taurine solution (1 g/50 mL) thrice a day for 4 weeks. Taurine was discontinued for the subsequent 4 weeks. The frequency and intensity of muscle cramps were evaluated using a questionnaire at weeks 0, 2, 4, 6, and 8 after the start of treatment. @*Results@#At baseline, the median frequency of muscle cramps was six times/week, and all patients had severe pain. Muscle cramp scores (frequency×intensity) decreased in seven patients by weeks 4 and 8 after treatment initiation. Compared to baseline muscle cramp scores [median 21, interquartile range (IQR): 8–84], median muscle cramp scores were lower at week 4 (6.5, IQR: 3–12, p=0.126) and week 8 (5, IQR: 1.5–56, p=0.066). All five patients whose baseline plasma taurine levels were below the normal limit showed increased taurine levels at week 4; 60% of them experienced improvements in their muscle cramps. Of the five patients with normal or higher taurine levels, 80% experienced an improvement in symptoms at week 4. The safety and tolerability of the 4-week taurine therapy were excellent. @*Conclusion@#Oral taurine therapy for 4 weeks improved muscle cramps safely in cirrhotic patients.
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Objective@#To assess the effect of left atrial appendage (LAA) isolation on LAA emptying and left atrial (LA) function using cardiac MRI in patients who underwent successful catheter ablation of atrial fibrillation (AF). @*Materials and Methods@#This retrospective study included 84 patients (mean age, 59 ± 10 years; 67 males) who underwent cardiac MRI after successful catheter ablation of AF. According to the electrical activity of LAA after catheter ablation, patients showed either LAA isolation or LAA normal activity. The LAA emptying phase (LAA-EP, in the systolic phase [SP] or diastolic phase), LAA emptying flux (LAA-EF, mL/s), and LA ejection fraction (LAEF, %) were evaluated by cardiac MRI. @*Results@#Of the 84 patients, 61 (73%) and 23 (27%) patients showed LAA normal activity and LAA isolation, respectively.Incidence of LAA emptying in SP was significantly higher in LAA isolation (91% vs. 0%, p < 0.001) than in LAA normal activation. LAA-EF was significantly lower in LAA isolation (40.1 ± 16.2 mL/s vs. 80.2 ± 25.1 mL/s, pp < 0.001) than in LAA normal activity. Furthermore, LAEF was significantly lower in LAA isolation (23.7% ± 11.2% vs. 31.1% ± 16.6%, p = 0.04) than in LAA normal activity. Multivariate analysis demonstrated that the LAA-EP was independent from LAEF (p = 0.01). @*Conclusion@#LAA emptying in SP may be a critical characteristic of LAA isolation, and it may adversely affect the LAEF after catheter ablation of AF.
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Computed tomography (CT) is an important imaging modality in evaluating thoracic malignancies. The clinical utility of dual-energy spectral computed tomography (DESCT) has recently been realized. DESCT allows for virtual monoenergetic or monochromatic imaging, virtual non-contrast or unenhanced imaging, iodine concentration measurement, and effective atomic number (Zeff map). The application of information gained using this technique in the field of thoracic oncology is important, and therefore many studies have been conducted to explore the use of DESCT in the evaluation and management of thoracic malignancies. Here we summarize and review recent DESCT studies on clinical applications related to thoracic oncology.
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Background/Aims@#The role of serum myokine levels in sarcopenia and the outcome of hepatocellular carcinoma (HCC) patients are not clear. This study investigated the serum levels of myostatin, follistatin, and interleukin-6 (IL-6) in HCC patients and their association with sarcopenia and survival. @*Methods@#Using prospectively collected pretreatment samples from 238 HCC patients in a hospital from 2012 to 2015, the serum levels of 3 myokines were determined and compared to 50 samples from age and sex-matched healthy controls. Sarcopenia was evaluated using the psoas muscle index (PMI) measured at the third lumbar level in the computed tomography, and clinical data were collected until 2017. @*Results@#The median levels of the 3 myokines for the male and female HCC patients were as follow: myostatin (3,979.3 and 2,976.3 pg/mL), follistatin (2,118.5 and 2,174.6 pg/mL), and IL-6 (2.5 and 2.7 pg/mL), respectively. Those in the HCC patients were all significantly higher than in the healthy controls. In the HCC patient, the median PMI was 4.43 (males) and 2.17 cm2/m2 (females) with a sarcopenic prevalence of 56.4%. The serum levels of myostatin, IL-6 and follistatin in the HCC patients showed a positive, negative, and no correlation with PMI, respectively. The serum follistatin level was an independent factor for poor survival in HCC patients. @*Conclusions@#The serum levels of myostatin, follistatin, and IL-6 and their correlation with sarcopenia and survival were presented in HCC patients for the first time. The role of the serum follistatin level as a poor prognostic biomarker warrants further study.
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Background/Aims@#We performed a large-scale, retrospective, nationwide, cohort study to investigate the risk factors for lung cancer among never-smoking Korean females. @*Methods@#The study data were collected from a general health examination and questionnaire survey of eligible populations conducted between January 1, 2003 and December 31, 2004; the data were acquired from the tailored big data distribution service of the National Health Insurance Service. After a 1-year clearance period, 5,860,922 of 6,318,878 never-smoking female participants with no previous history of lung cancer were investigated. After a median follow-up of 11.4 years, 43,473 (0.74%) participants were defined as “newly diagnosed lung cancer”. @*Results@#After adjusting for all variables at baseline, the variables older age, lower body mass index (BMI), less exercise, frequent alcohol drinking, meat-based diet, rural residence, and previous history of cancer were associated with a higher incidence of lung cancer. Low BMI (< 18.5 kg/m2: hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.27 to 1.40) was a significant independent risk factor; as BMI decreased, HR increased. Negative associations between BMI and lung-cancer development were also observed after controlling for age (p for trend < 0.001). Drinking alcohol one to two times a week (HR, 1.25; 95% CI, 1.21 to 1.28) and eating a meat-based diet (HR, 1.08; 95% CI, 1.01 to 1.15) were associated with lung-cancer incidence. @*Conclusions@#Modifiable baseline characteristics, such as BMI, exercise, alcohol consumption, and diet, are risk factors for lung-cancer development among never- smoking females. Thus, lifestyle modifications may help prevent lung cancer.
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Lung cysts are commonly seen on computed tomography (CT), and cystic lung diseases show a wide disease spectrum. Thus, correct diagnosis of cystic lung diseases is a challenge for radiologists. As the first diagnostic step, cysts should be distinguished from cavities, bullae, pneumatocele, emphysema, honeycombing, and cystic bronchiectasis. Second, cysts can be categorized as single/localized versus multiple/diffuse. Solitary/localized cysts include incidental cysts and congenital cystic diseases. Multiple/diffuse cysts can be further categorized according to the presence or absence of associated radiologic findings. Multiple/diffuse cysts without associated findings include lymphangioleiomyomatosis and Birt-Hogg-Dubé syndrome. Multiple/diffuse cysts may be associated with ground-glass opacity or small nodules. Multiple/diffuse cysts with nodules include Langerhans cell histiocytosis, cystic metastasis, and amyloidosis. Multiple/diffuse cysts with ground-glass opacity include pneumocystis pneumonia, desquamative interstitial pneumonia, and lymphocytic interstitial pneumonia. This stepwise radiologic diagnostic approach can be helpful in reaching a correct diagnosis for various cystic lung diseases.
Subject(s)
Amyloidosis , Birt-Hogg-Dube Syndrome , Bronchiectasis , Diagnosis , Emphysema , Histiocytosis , Histiocytosis, Langerhans-Cell , Lung Diseases , Lung Diseases, Interstitial , Lung , Lymphangioleiomyomatosis , Neoplasm Metastasis , Pneumonia, PneumocystisABSTRACT
Atrial fibrillation (AF) is the most common arrhythmia associated with the risk of morbidity and mortality in clinical patients. AF is considered as an arrhythmia type that develops and progresses through close connection with cardiac structural arrhythmogenic substrates. Since the introduction of catheter ablation-mediated electrical isolation of arrhythmogenic substrates, cardiac imaging indicates improved treatment outcome and prognosis with appropriate candidate selection, ablation catheter guidance, and post-ablation follow-up. Currently, cardiac computed tomography (CCT) and cardiovascular magnetic resonance (CMR) imaging are essential in the case management of AF at both pre-and post-procedural stages of catheter ablation. In this review, we discuss the roles and technical considerations of CCT and CMR imaging in the management of patients with AF undergoing catheter ablation.
Subject(s)
Humans , Arrhythmias, Cardiac , Atrial Fibrillation , Case Management , Catheter Ablation , Catheters , Follow-Up Studies , Magnetic Resonance Imaging , Mortality , Prognosis , Treatment OutcomeABSTRACT
Rapid advances in cardiac computed tomography (CT) have enabled the characterization of left ventricular (LV) myocardial diseases based on LV anatomical morphology, function, density, and enhancement pattern. Global LV function and regional wall motion can be evaluated using multi-phasic cine CT images. CT myocardial perfusion imaging facilitates the identification of hemodynamically significant coronary artery disease. CT delayed-enhancement imaging is used to detect myocardial scar in myocardial infarction and to measure the extracellular volume fraction in non-ischemic cardiomyopathy. Multi-energy cardiac CT allows the mapping of iodine distribution in the myocardium. This review summarizes the current techniques of cardiac CT for LV myocardial assessment, highlights the key findings in various myocardial diseases, and presents future applications to complement echocardiography and cardiovascular magnetic resonance.
Subject(s)
Cardiomyopathies , Cicatrix , Complement System Proteins , Coronary Artery Disease , Echocardiography , Iodine , Myocardial Infarction , Myocardial Perfusion Imaging , Myocardium , Tomography, X-Ray ComputedABSTRACT
PURPOSE@#To demonstrate the relationship between epicardial fat accumulation and left atrial reverse remodeling by cardiac multi-detector CT (MDCT) after catheter ablation of atrial fibrillation (AF).@*MATERIALS AND METHODS@#Seventy-six patients underwent cardiac MDCT before and after catheter ablation of AF. Left atrial volume (LAV) and epicardial fat volume (EFV) were measured. LAV and EFV before and after catheter ablation of AF were respectively compared and the change percentages (CPs) were evaluated.@*RESULTS@#The LAV after catheter ablation of AF was significantly less than the baseline LAV (107.5 ± 50.2 mL vs. 144.9 ± 62.6 mL, p < 0.001). The EFV after catheter ablation of AF was significantly greater than the baseline EFV (105.0 ± 35.6 mL vs. 90.1 ± 31.9 mL, p < 0.001). Mean CPs of LAV and EFV were −23.3% ± 20.8% and 15.9% ± 20.9%, respectively. There was a significantly negative relationship between the CPs of LAV and EFV (R = −0.53, p < 0.001).@*CONCLUSION@#Catheter ablation of AF may result in a reduction in LAV and an increase in EFV. Left atrial reverse remodeling with a reduction in LAV may be associated with epicardial fat accumulation in patients who undergo catheter ablation of AF.
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Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor of the thyroid gland mostly occurring in young patients. The imaging findings of SETTLE tumors are yet to be defined. However, they are usually described as well-defined heterogeneously enhanced masses on CT scan. The current case has the potential growth as compared with a 2009 chest radiography. We took into account the possibility of SETTLE in the case of a bulky mass in patients over 70 years old, particularly in the lower neck. Herein, we report a case of the oldest patient so far. The patient underwent a right lobectomy of the thyroid and mass excision. Follow-up CT scans after 6 months revealed no local recurrence. Surgery is the gold standard treatment for SETTLE. Chemotherapy and radiotherapy could be another possible option for patients with advanced stage SETTLE.
Subject(s)
Aged , Humans , Drug Therapy , Follow-Up Studies , Neck , Radiography , Radiotherapy , Recurrence , Thorax , Thyroid Gland , Thyroid Neoplasms , Tomography, X-Ray ComputedABSTRACT
Aspiration is defined as accidental entrance of foreign matter into the lower respiratory tract, and is a common event and can occur in healthy individuals. The type of aspiration-induced lung diseases depends on the quantity and nature of the aspirated material, the chronicity, and the host responses. Aspiration into the airways and lungs can cause a wide spectrum of lung diseases with various manifestations in adults. Diseases with predominantly airway manifestation include foreign body aspiration and diffuse aspiration bronchiolitis. Diseases with predominantly lung parenchymal manifestation include acute diseases such as aspiration pneumonia, aspiration pneumonitis, and near drowning, and chronic diseases such as chronic exogenous lipoid pneumonia and chronic interstitial lung disease. Definitive diagnosis of aspiration-induced lung diseases is challenging to make. Awareness of radiologic findings associated with these diseases is essential for accurate diagnosis and management of these diverse aspiration-induced lung diseases.
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BACKGROUND: Korean National Health Insurance reimburses factor VIII (FVIII) and factor IX (FIX) clotting factor concentrate (CFC) infusions to discrepant activity levels, allowing elevation of FVIII activity to 60 IU/dL and FIX to 40 IU/dL. We aimed to assess hemostatic response to these target levels using global hemostatic assays. METHODS: We enrolled 34 normal healthy men, 34 patients with hemophilia A, and 36 with hemophilia B, with residual factor activity of 3 IU/dL or less and without inhibitors. Patients with hemophilia A and B received injected CFCs according to reimbursement guidelines. Fifteen minutes after injection, we assessed hemostatic response with global hemostatic assays: thrombin generation assay (TGA), thromboelastography (TEG), and clot waveform analysis (CWA). RESULTS: Normal healthy men and patients with hemophilia A and B were 36.7, 37.2, and 35.1 years old, respectively. FVIII and recombinant FIX concentrate doses were 28.8 IU/kg and 43.6 IU/kg. Post-infusion FVIII activity rose from 0.5 IU/dL to 69.4 IU/dL, while FIX activity rose from 1.4 IU/dL to 46.8 IU/dL. Post-infusion peak thrombin concentrations in hemophilia A and B were 116.6 nM/L and 76.4 nM/L (P < 0.001). Post-infusion endogenous thrombin potential (ETP) in hemophilia A and B was 1349.8 nM/min and 915.6 nM (P < 0.001). TEG index of hemophilia A and B was 0.11 and −0.51 (P=0.006). CONCLUSION: Current reimbursed doses for FIX concentrates are insufficient to achieve hemostatic responses comparable to those after reimbursed doses for FVIII concentrates in terms of peak thrombin concentration, ETP, and TEG index.