The adaptability of the Pulsta valve to the diverse main pulmonary artery shape of native right ventricular outflow tract disease.

BACKGROUND: Pulsta valve is increasingly used for percutaneous pulmonary valve implantation (PPVI) in patients with a large native right ventricular outflow tract (RVOT). This study aims to elucidate the outcomes of Pulsta valve implantation within the native RVOT and assess its adaptability to various native main pulmonary artery (PA) anatomies. METHODS: A multicenter retrospective study included 182 patients with moderate to severe pulmonary regurgitation in the native RVOT who underwent PPVI with Pulsta valves® between February 2016 and August 2023 at five Korean and Taiwanese tertiary referral centers. RESULTS: Pulsta valve implantation was successful in 179 out of 182 patients (98.4%) with an average age of 26.7 ± 11.0 years. The median follow-up duration was 29 months. Baseline assessments revealed enlarged right ventricle (RV) volume (mean indexed RV end-diastolic volume: 163.1 (interquartile range, IQR: 152.0-180.3 mL/m²), which significantly decreased to 123.6(IQR: 106.6-137.5 mL/m2  after 1 year. The main PA types were classified as pyramidal (3.8%), straight (38.5%), reverse pyramidal (13.2%), convex (26.4%), and concave (18.1%) shapes. Pulsta valve placement was adapted, with distal main PA for pyramidal shapes and proximal or mid-PA for reverse pyramidal shapes. Two patients experienced Pulsta valve embolization to RV, requiring surgical removal, and one patient encountered valve migration to the distal main PA, necessitating surgical fixation. CONCLUSIONS: Customized valve insertion sites are pivotal in self-expandable PPVI considering diverse native RVOT shape. The rather soft and compact structure of the Pulsta valve has characteristics to are adaptable to diverse native RVOT geometries.

N-(2,3-dihydroxypropyl) carbamoyl side chain: a potentially significant factor for recurrent iodinated contrast medium-related adverse drug reactions.

PURPOSE: To determine whether switching to contrast media based on the sharing of N-(2,3-dihydroxypropyl) carbamoyl side chain reduces the recurrence of iodinated contrast media (ICM)-associated adverse drug reactions (ADRs). MATERIALS AND METHODS: This single-center retrospective study included 2133 consecutive patients (mean age ± SD, 56.1 ± 11.4 years; male, 1052 [49.3%]) who had a history of ICM-associated ADRs and underwent contrast-enhanced CT examinations. The per-patient and per-exam-based recurrence ADR rates were compared between cases of switching and non-switching the ICM from ICMs that caused the previous ADRs, and between cases that used ICMs with common and different carbamoyl side chains from ICMs that caused the previous ADRs. Downgrade rates (no recurrence or the occurrence of ADR less severe than index ADRs) were also compared. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were additionally performed. RESULTS: In per-patient analysis, switching of ICM showed a lower recurrence rate (switching, 10.4% [100/965] vs. non-switching, 28.4% [332/1168]), with the adjusted odds ratio (OR) of 0.27 (95% CI: 0.21, 0.34; p < 0.001). The result was consistent in PSM (OR, 0.29 [95% CI: 0.22, 0.39]; p < 0.001), IPTW (OR, 0.28 [95% CI: 0.22, 0.36]; p < 0.001), and in per-exam analysis (5.5% vs. 13.8%; OR, 0.32 [95% CI: 0.27, 0.37]; p < 0.001). There was lower per-exam recurrence (5.0% [195/3938] vs. 7.8% [79/1017]; OR, 0.63 [95% CI: 0.47, 0.83]; p = 0.001) and higher downgrade rates (95.6% [3764/3938] vs. 93.3% [949/1017]; OR, 1.51 [95% CI: 1.12, 2.03]; p = 0.006) when using different side chain groups. CONCLUSION: Switching to an ICM with a different carbamoyl side chain reduced the recurrent ADRs and their severity during subsequent examinations. CLINICAL RELEVANCE STATEMENT: Switching to an iodinated contrast media with a different carbamoyl side chain reduced the recurrent adverse drug reactions and their severity during subsequent examinations.

Pediatric Extracorporeal Membrane Oxygenation in Korea: A Multicenter Retrospective Study on Utilization and Outcomes Spanning Over a Decade.

BACKGROUND: Over the last decade, extracorporeal membrane oxygenation (ECMO) use in critically ill children has increased and is associated with favorable outcomes. Our study aims to evaluate the current status of pediatric ECMO in Korea, with a specific focus on its volume and changes in survival rates based on diagnostic indications. METHODS: This multicenter study retrospectively analyzed the indications and outcomes of pediatric ECMO over 10 years in patients at 14 hospitals in Korea from January 2012 to December 2021. Four diagnostic categories (neonatal respiratory, pediatric respiratory, post-cardiotomy, and cardiac-medical) and trends were compared between periods 1 (2012-2016) and 2 (2017-2021). RESULTS: Overall, 1065 ECMO runs were performed on 1032 patients, with the annual number of cases remaining unchanged over the 10 years. ECMO was most frequently used for post-cardiotomy (42.4%), cardiac-medical (31.8%), pediatric respiratory (17.5%), and neonatal respiratory (8.2%) cases. A 3.7% increase and 6.1% decrease in pediatric respiratory and post-cardiotomy cases, respectively, were noted between periods 1 and 2. Among the four groups, the cardiac-medical group had the highest survival rate (51.2%), followed by the pediatric respiratory (46.4%), post-cardiotomy (36.5%), and neonatal respiratory (29.4%) groups. A consistent improvement was noted in patient survival over the 10 years, with a significant increase between the two periods from 38.2% to 47.1% (P = 0.004). Improvement in survival was evident in post-cardiotomy cases (30-45%, P = 0.002). Significant associations with mortality were observed in neonates, patients requiring dialysis, and those treated with extracorporeal cardiopulmonary resuscitation (P < 0.001). In pediatric respiratory ECMO, immunocompromised patients also showed a significant correlation with mortality (P < 0.001). CONCLUSION: Pediatric ECMO demonstrated a steady increase in overall survival in Korea; however, further efforts are needed since the outcomes remain suboptimal compared with global outcomes.

Predictive Scoring System for Spontaneous Closure of Infant Ventricular Septal Defect: The P-VSD Score.

Ventricular septal defect (VSD) is a common congenital heart disease. However, consensus on the utility of echocardiography in predicting spontaneous closure (SC) of VSD remains lacking. This study aimed to identify and validate significant predictors of SC through a predictive scoring system. This retrospective study included medical records of 712 echocardiography instances performed on 304 patients diagnosed with VSD from 2016 to 2020 in their first year of life. A novel scoring system for predicting the SC of VSD was developed and validated using another dataset from different hospitals. Of the 304 patients, 215 (70.7%) had perimembranous (PM) VSDs and 89 had muscular (29.3%) VSDs. The median follow-up periods were 36.2 (interquartile range [IQR], 13-59) months and 13.7 9 (IQR, 5-37.4) days for PM and muscular VSDs, respectively. The overall SC rate during follow-up was 29.3%. Pulmonary hypertension (HTN), concomitant left ventricle (LV)-right atrium (RA) shunt, VSD size to aortic valve (AV) annulus size ratio, and left ventricular end-diastolic dimension (LVEDD) z-score were significant risk factors affecting SC of VSD. The "P-VSD" score, a new scoring system, demonstrated an area under the curve for predictability of 0.769. Pulmonary HTN, concomitant LV-RA shunt, LVEDD z-score, and VSD size-to-AV annulus size ratio at diagnosis were significantly associated with non-SC VSD after infancy. The P-VSD score can predict the SC of VSD in clinical settings and simplify the identification and appropriate management of high-risk patients.

Development of a Rapid Detection Method for Ethylene Glycol and Glycolic Acid in Feline Samples: A Response to Increasing Antifreeze Poisoning Incidents in Korea.

Recently, cases of antifreeze poisoning in companion animals, particularly cats, have surged in the Republic of Korea. Ethylene glycol (EG), the toxic primary component of antifreeze, is metabolized into glycolic acid (GA), leading to severe metabolic acidosis, acute kidney injury, and death. Traditional detection methods, although effective, are often time-consuming owing to complex sample preparation. This study involved a novel analytical method utilizing GC-MS for EG and LC-MS/MS for GA detection, which streamlined the detection process by eliminating the need for derivatization. The method was validated for accuracy and reliability, enabling the rapid and precise identification of EG and GA in biological samples. This study also included the successful application of this method in a case where initial exposure to antifreeze was not apparent, which highlighted the effectiveness of this method in diagnosing poisoning even in cases where clinical history is unclear. The development of this rapid diagnostic approach addresses the urgent need for the efficient detection of antifreeze poisoning, improving animal welfare and supporting forensic investigations.

Serotype-specific transduction of canine joint tissue explants and cultured monolayers by self-complementary adeno-associated viral vectors.

A formal screening of self-complementary adeno-associated virus (scAAV) vector serotypes in canine joint tissues has not been performed to date. Selecting appropriate serotypes is crucial for successful treatment due to their varying levels of tissue tropism. The objective of this study is to identify the most optimal scAAV vector serotype that maximizes transduction efficiencies in canine cell monolayer cultures (chondrocytes, synoviocytes, and mesenchymal stem cells) and tissue explant cultures (cartilage and synovium). Transduction efficiencies of scAAV serotypes 1, 2, 2.5, 3, 4, 5, 6, 8, and 9 were evaluated in each culture type in three different vector concentrations by encoding a green fluorescent protein. It was found that scAAV2 and 2.5 showed the overall highest transduction efficiency among serotypes with dose-response. Since possible immune response against conventional AAV2 was previously reported in dogs, the chimeric scAAV2.5 may be more suitable to use. Evaluation of the safety and efficacy of the scAAV2.5 vector with an appropriate therapeutic gene in vivo is indicated.

Automatic Depression Detection Using Smartphone-Based Text-Dependent Speech Signals: Deep Convolutional Neural Network Approach.

BACKGROUND: Automatic diagnosis of depression based on speech can complement mental health treatment methods in the future. Previous studies have reported that acoustic properties can be used to identify depression. However, few studies have attempted a large-scale differential diagnosis of patients with depressive disorders using acoustic characteristics of non-English speakers. OBJECTIVE: This study proposes a framework for automatic depression detection using large-scale acoustic characteristics based on the Korean language. METHODS: We recruited 153 patients who met the criteria for major depressive disorder and 165 healthy controls without current or past mental illness. Participants' voices were recorded on a smartphone while performing the task of reading predefined text-based sentences. Three approaches were evaluated and compared to detect depression using data sets with text-dependent read speech tasks: conventional machine learning models based on acoustic features, a proposed model that trains and classifies log-Mel spectrograms by applying a deep convolutional neural network (CNN) with a relatively small number of parameters, and models that train and classify log-Mel spectrograms by applying well-known pretrained networks. RESULTS: The acoustic characteristics of the predefined text-based sentence reading automatically detected depression using the proposed CNN model. The highest accuracy achieved with the proposed CNN on the speech data was 78.14%. Our results show that the deep-learned acoustic characteristics lead to better performance than those obtained using the conventional approach and pretrained models. CONCLUSIONS: Checking the mood of patients with major depressive disorder and detecting the consistency of objective descriptions are very important research topics. This study suggests that the analysis of speech data recorded while reading text-dependent sentences could help predict depression status automatically by capturing the characteristics of depression. Our method is smartphone based, is easily accessible, and can contribute to the automatic identification of depressive states.

Outbreak of severe diarrhea due to zoonotic Cryptosporidium parvum and C. xiaoi in goat kids in Chungcheongbuk-do, Korea.

Severe diarrhea was reported in goat kids in Chungcheongbuk-do, Korea, from 2021 to 2023, and Cryptosporidium infection was suspected. To confirm the cause of this outbreak, fecal samples were collected from goat farms where diarrhea had been reported and analyzed for Cryptosporidium infection using a molecular assay. A total of 65 fecal samples, including 37 from goats with diarrhea and 28 from goats without diarrhea, were collected from six goat farms. Forty-eight of the goats were kids (<2 months) and 17 were adults (>1 year). Cryptosporidium was identified in 53.8% (35/65) of total samples. Overall, 86.5% (32/37) of the diarrheic fecal samples tested positive; however, Cryptosporidium was not detected in any fecal sample from non-diarrheic adult goats. Therefore, cryptosporidiosis was significantly associated with diarrhea in goat kids, and adult goats were not responsible for transmission of Cryptosporidium to them. Phylogenetic analysis and molecular characterization revealed two Cryptosporidium species, namely, C. parvum (n = 28) and C. xiaoi (n = 7). In the C. parvum-positive samples, gp60 gene analysis revealed three zoonotic subtypes-IIaA18G3R1, IIdA15G1, and IIdA16G1. To the best of our knowledge, this study is the first to identify C. parvum IIaA18G3R1 and IIdA16G1 in goats, as well as the first to identify C. xiaoi in goats in Korea. These results suggest that goat kids play an important role as reservoir hosts for different Cryptosporidium species and that continuous monitoring with biosecurity measures is necessary to control cryptosporidiosis outbreaks.

The impact of aromatherapy-based oral care on oral conditions, salivary pH, and halitosis in older adults with dementia: Pilot study.

Inadequate oral care and poor oral health in older adults are known to increase the risk of dementia. Dementia patients residing in long-term care facilities are especially vulnerable to oral diseases due to their care-resistant behavior. This study aimed to investigate the effects of a 7-day oral care program based on an aroma solution in 58 dementia patients (29 each in the experimental and control groups) admitted to a long-term care hospital in South Korea. The experimental group received oral care with a solution containing peppermint, tea tree, and lemon essential oils, and the control group with a saline solution. The effectiveness of oral care was assessed by the participants' oral condition, salivary pH, and halitosis. The experimental group showed significant improvements (P<.001) in all three outcomes, indicating that oral care with an aroma solution can improve the oral health of older dementia patients residing in long-term care facilities.

Clinical manifestations of COVID-19 breakthrough infections: A systematic review and meta-analysis.

To provide a comparative meta-analysis and systematic review of the risk and clinical outcomes of coronavirus 2019 (COVID-19) infection between fully vaccinated and unvaccinated groups. Eighteen studies of COVID-19 infections in fully vaccinated ("breakthrough infections") and unvaccinated individuals were reviewed from Medline/PubMed, Scopus, Embase, and Web of Science databases. The meta-analysis examined the summary effects and between-study heterogeneity regarding differences in the risk of infection, hospitalization, treatments, and mortality between vaccinated and unvaccinated individuals. he overall risk of infection was lower for the fully vaccinated compared to that of the unvaccinated (relative risk [RR] 0.20, 95% confidence interval [CI]: 0.19-0.21), especially for variants other than Delta (Delta: RR 0.29, 95% CI: 0.13-0.65; other variants: RR 0.06, 95% CI: 0.04-0.08). The risk of asymptomatic infection was not statistically significantly different between fully vaccinated and unvaccinated (RR 0.56, 95% CI: 0.27-1.19). There were neither statistically significant differences in risk of hospitalization (RR 1.06, 95% CI: 0.38-2.93), invasive mechanical ventilation (RR 1.65, 95% CI: 0.90-3.06), or mortality (RR 1.19, 95% CI: 0.79-1.78). Conversely, the risk of supplemental oxygen during hospitalization was significantly higher for the unvaccinated (RR 1.40, 95% CI: 1.08-1.82). Unvaccinated people were more vulnerable to COVID-19 infection than fully vaccinated for all variants. Once infected, there were no statistically significant differences in the risk of hospitalization, invasive mechanical ventilation, or mortality. Still, unvaccinated showed an increased need for oxygen supplementation. Further prospective analysis, including patients' risk factors, COVID-19 variants, and the utilized treatment strategies, would be warranted.

Effects of polycyclic aromatic hydrocarbons on the proliferation and differentiation of placental cells.

BACKGROUND: The purpose of this study was to investigate the effects of polycyclic aromatic hydrocarbons (PAHs) other than bisphenol A (BPA) and BPA substitutes on placental cells. METHODS: HTR-8/SVneo cells were treated with anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol, which is used as a substitute for BPA-free products. After confirming the dose response for each reagent using the prepared cells, the cells were incubated for 24, 48, and 72 h. Cell viability was confirmed using the XTT assay. Each experiment was performed with the minimum number of samples (n = 3) required for statistical analysis. The results were analyzed using t-tests; p < 0.05 was considered statistically significant. RESULTS: After treatment with anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol, the absorbance measured using the XTT assay decreased significantly with increasing concentration. The absorbance decreased significantly over time following treatment with each endocrine disruptor at the concentration confirmed by the dose-response analysis. CONCLUSIONS: This study showed that anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol-a BPA substitute-affect cell viability and necrosis in the placental cell line. The study indicates the serious effects of PAHs that negatively affect pregnancy but were previously unknown. Further, this study would serve as a reference for the identification of harmful PAHs during pregnancy prognosis in women who are more susceptible to PAH exposure.

Appendicular skeletal muscle mass assessment in dogs: a scoping literature review.

BACKGROUND: Monitoring changes in appendicular skeletal muscle mass is frequently used as a surrogate marker for limb function. The primary objective of this study was to review scientific information related to the assessment of appendicular skeletal muscle mass in dogs. The secondary objective was to develop practical recommendations for serial evaluation of muscle mass. METHODS: A scoping review was conducted with a systematic search of PubMed, Web of Science, CAB abstract, and Cochrane from inception to June 2021. The following modalities were included in the search: limb circumference, diagnostic ultrasound, computed tomography, magnetic resonance imaging, and dual-energy x-ray absorptiometry. RESULTS: A total of 62 articles that measured appendicular skeletal muscle mass in dogs were identified. Limb circumference (55 articles) was the most commonly used modality. Its reliability was investigated in five studies. Several factors, including measuring tape type, body position, joint angles, and the presence of hair coat, were reported as variables that can affect measurements. Diagnostic ultrasound (five articles) was validated in three articles, but there is scarce information about observer reliability and variables affecting the measurement. Computed tomography (four articles) and magnetic resonance imaging (one article) have been used to validate other modalities at a single time point rather than as a clinical tool for serial muscle mass monitoring. Dual-energy x-ray absorptiometry (two articles) has been used to quantify specific skeletal muscle mass but was mainly used to evaluate body composition in dogs. CONCLUSION: Limb circumference and ultrasound are likely the main modalities that will continue to be used for serial muscle mass measurement in the clinical setting unless a new technology is developed. The reliability of limb circumference is questionable. Several key factors, including measuring tape type, body position, joint angles, and coat clipping, need to be controlled to improve the reliability of limb circumference measurements. Ultrasound may provide a reasonable alternative, but further studies are required to evaluate the reliability of this modality and identify factors that influence ultrasound measurements.

Identification of essential element determining fruit-specific transcriptional activity in the tomato HISTIDINE DECARBOXYLASE A gene promoter.

KEY MESSAGE: In SlHDC-A promoter, SlHDC-A core-ES is an essential region for fruit-specific expression and interacts with GATA, HSF and AP1. Triplication of essential region was proposed as a minimal fruit-specific promoter. In plant biotechnology, fruit-specific promoter is an important tool for the improvement and utilization of tomato fruit. To expand our understanding on fruit-specific expression, it is necessary to determine the promoter region involved in fruit-specific transcriptional activity and transcriptional regulations of the promoter. In previous study, we isolated a fruit-specific SlHDC-A core promoter specifically expressed during tomato ripening stages. In this study, we identified SlHDC-A promoter region (SlHDC-A core-ES) that is essential for fruit-specific expression of the SlHDC-A. To understand the molecular mechanisms of fruit-specific expression of the SlHDC-A promoter, we first identified the putative transcription factor binding elements in the SlHDC-A core promoter region and corresponding putative transcription factors which are highly expressed during fruit maturation. Yeast one hybrid analysis confirmed that GATA, HSF, and AP1 interact with the SlHDC-A core-ES promoter region. Further transactivation analysis revealed that expression of the three transcription factors significantly activated expression of a reporter gene driven by SlHDC-A core-ES promoter. These results suggest that GATA, HSF, and AP1 are involved in the fruit-specific expression of SlHDC-A promoter. Furthermore, the synthetic promoter composed of three tandem repeats of SlHDC-A core-ES showed relatively higher activity than the constitutive 35S promoter in the transgenic tomato fruits at the orange stage. Taken together, we propose a new synthetic promoter that is specifically expressed during fruit ripening stage.

Health disparity and healthcare utilization inequity among older adults living in poverty in South Korea: a cross-sectional study.

BACKGROUND: Korea has a two-tiered universal health security system: the wage-based National Health Insurance (NHI) program and government-subsidized Medical Aid (MA) program. Beneficiaries of the MA program belong to the lowest economic class. This study aims to investigate the association between economic status-defined as NHI or MA enrollment-and health disparity of older people aged ≥ 65 years in South Korea. METHODS: The claims records of 672,525 older age population from the 2017 Health Insurance Review and Assessment Service-Adult Patient Sample were used to estimate adjusted odds ratios (aORs) of MA vs. NHI beneficiaries for prevalence for common geriatric diseases. Logistic regression and negative binomial regression were used to investigate the association between economic status and prevalence or healthcare utilization for each disease. RESULTS: MA beneficiaries showed significantly higher prevalence than NHI beneficiaries for seven out of nine diseases (aORs ranging from 1.18 to 1.95). The discrepancy in the prevalence between the two groups was highest among those aged 65-69 years (aORs: 1.34-2.94), and diminished as they got older (aORs: 1.05-1.67). MA beneficiaries had significantly more outpatient visits to treat six diseases (aORs: 1.07-1.28), and more hospitalization to treat seven diseases (aORs:1.08-1.73) than NHI beneficiaries. CONCLUSION: The higher prevalence of common geriatric diseases among MA than NHI beneficiaries confirms unfavorable health disparity in the elderly living in extreme poverty. Similar or higher healthcare utilization in treating the same conditions among MA beneficiaries suggests a low possibility of inequity for access to healthcare resources covered by the universal health security system due to poor economic status. Greater excess use of inpatient than outpatient care by MA beneficiaries implies that the condition of poor older adults might be more severe when diagnosed with the same disease.

Verbal violence and turnover intention among new nurses in Korea: A time-lagged survey.

AIM: To test a model examining the impact of verbal violence against new nurses on their turnover intention and the mediating effects of emotional reaction and burnout based on affective events theory. BACKGROUND: In Korea, turnover rate of nurses, especially new nurses, is at a serious level. It is important to verify the paths by which nurses reach a turnover intention after experiencing verbal violence, which is the most common form of workplace violence. In particular, research on new nurses who are vulnerable to exposure to verbal violence and have a high turnover rate is insufficient. METHODS: Data were collected using time-lagged online surveys from 212 Korean new nurses. Structural equation modelling was used to test the hypothesized model. RESULTS: The level of the turnover intention of new nurses was almost 4 out of 5. Verbal violence not only has a direct effect on turnover intention but also has an indirect effect through burnout. Emotional reactions and burnout sequentially mediated the relationship between verbal violence and turnover intention; these variables explained approximately 57% of turnover intention. CONCLUSIONS: To decrease negative emotional reactions and burnout caused by verbal violence may benefit to reduction of turnover intention of new nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Our finding highlight the critical need for new nurses' violence interventions that focus on emotional reactions and burnout, and thereby improving desirable patient-co-worker-nurse relationships and quality of life for new nurses.

Cost-utility analysis of emicizumab prophylaxis in haemophilia A patients with factor VIII inhibitors in Korea.

AIMS: Haemophilia A patients with factor VIII inhibitors (HAPI) experience frequent spontaneous bleeding, approximately once a week, and require expensive bypassing agent (BPA) treatments to control bleeding over their lifetime. According to the HAVEN 1 trial, weekly emicizumab (Hemlibra®) prophylaxis injection reduces annualized bleeding rates (ABR) by 87% compared with BPA on-demand treatment (BPA-OD) administered at the time of bleeding. Our study aimed to assess the cost-effectiveness of emicizumab prophylaxis in HAPI in Korea. METHODS: Using a lifetime Markov model with health states of 'alive with bleeds' and 'dead', we simulated the experience of HAPI receiving emicizumab prophylaxis (treatment arm) or BPA-OD (control arm) and estimated expected clinical and economic outcomes under each treatment arm. Model parameters included comparative effectiveness, clinical and epidemiologic characteristics of Korean HAPI, costs of drug treatment and medical events and utility for 'alive with bleeds' state under each treatment. We utilized local data, including National Health Insurance claims data, national statistics, literature and expert surveys with haematologists. RESULTS: Base-case analysis results showed that compared with BPA-OD, lifetime emicizumab prophylaxis prevented 807 bleedings, extended 3.04 quality-adjusted life-years and reduced costs by 2.6 million US dollars. Thus, emicizumab prophylaxis is a dominant treatment option with better effectiveness and lower costs than BPA-OD. A series of one-way sensitivity analyses consistently showed dominant results, confirming that lifetime emicizumab prophylaxis is a cost-saving intervention for HAPI. CONCLUSION: Emicizumab prophylaxis is an excellent treatment choice reducing ABR, improving quality of life and reducing costs.

Considerations on the Implementation of the Telemedicine System Encountered with Stakeholders' Resistance in COVID-19 Pandemic.

Background: Non-face-to-face consultation, which ensures physical distance between patients and doctors, is increasing as a substitute mode for dealing with highly infectious diseases. Korea, with its remarkable Information and Communications Technology infrastructure, introduced telemedicine in 1988, yet it has not been formally accepted owing to stakeholders' resistance and legal restrictions. Purpose: This study aims to determine the feasibility of implementing the telemedicine system and find solutions of its development and resistance by stakeholders. Method and Material: The authors present a unique case of Korea where telemedicine, despite its solid technological base, has not yet gained a foothold 32 years after its first pilot project. A narrative review was condected according to the timeline of government-driven telemedicine adoption in Korea, and an analysis was performed on the tendency of stakeholder resistance. Results: The analysis revealed that the relevant stakeholders were classified into doctors, patients, governments and some political parties. Among stakeholders as a whole, private healthcare physicians, who provide over 90% of primary care in Korea, amount to the largest demographic against the implementation of telemedicine. Their resistance was found to be the product of policies and problems arising from the coexistence of telemedicine and conventional healthcare regimes. With the COVID-19 pandemic, policymakers are at odds with these stakeholders while implementing a pilot project. Conclusion: Fostering smooth policy implementation necessitates adopting an approach that reduces conflicts with private healthcare providers.

Accumulation of Mitochondrial RPPH1 RNA Is Associated with Cellular Senescence.

Post-transcriptional gene regulation is an important step in the regulation of eukaryotic gene expression. Subcellular compartmentalization of RNA species plays a crucial role in the control of mRNA turnover, spatial restriction of protein synthesis, and the formation of macromolecular complexes. Although long noncoding RNAs (lncRNAs) are one of the key regulators of post-transcriptional gene expression, it is not heavily studied whether localization of lncRNAs in subcellular organelles has functional consequences. Here, we report on mitochondrial lncRNAs whose expression fluctuates in the process of cellular senescence. One of the mitochondrial lncRNAs, RPPH1 RNA, is overexpressed and accumulates in mitochondria of senescent fibroblasts, possibly modulated by the RNA-binding protein AUF1. In addition, RPPH1 RNA overexpression promotes spontaneous replicative cellular senescence in proliferating fibroblasts. Using MS2 aptamer-based RNA affinity purification strategy, we identified putative target mRNAs of RPPH1 RNA and revealed that partial complementarity of RPPH1 RNA to its target mRNAs prevents those mRNAs decay in proliferating fibroblasts. Altogether, our results demonstrate the role of mitochondrial noncoding RNA in the regulation of mRNA stability and cellular senescence.

Supplementary Anal Imaging by Magnetic Resonance Enterography in Patients with Crohn's Disease Not Suspected of Having Perianal Fistulas.

BACKGROUND & AIMS: Few data are available to guide the use of anal imaging for patients with Crohn's disease (CD) who are not suspected of having perianal fistulas. We aimed to evaluate the role of anal imaging supplementary to magnetic resonance enterography (MRE) in these patients. METHODS: In a prospective study, we added a round of anal MR imaging (MRI), collecting axial images alone, to MRE evaluation of 451 consecutive adults who were diagnosed with or suspected of having CD but not believed to have perianal fistulas. Images were examined for perianal tracts; if present, colorectal surgeons reexamined patients to identify external openings or perianal inflammation or abscess. Patients were followed and data were collected on dedicated treatment for perianal fistulas or abscess. We calculated the diagnostic yield for anal MRI, associated factors, and outcomes of MRI-detected asymptomatic perianal tracts. RESULTS: A total of 440 patients (mean age, 29.6±8.9 years) met the inclusion criteria. Anal MRI revealed perianal tracts in 53 patients (12%; 95% CI, 9.3%-15.4%). Surgeons however did not identify any lesions that required treatment. The asymptomatic tracts were mostly single unbranched (83%), inter-sphincteric (72%), or had a linear dark signal at the tract margin (79%). Younger age at MRE, female sex, and CD activity index scores of 220-450 were independently associated with detection of perianal tracts. MRI detection of asymptomatic tracts was independently associated with later development of perianal fistulas or abscess that required treatment: 17.8% cumulative incidence at 37 months and an adjusted hazard ratio of 3.06 (95% CI, 1.01-9.27; P = .048). CONCLUSIONS: In a prospective study of patients with CD, we found that adding anal MRI evaluation to MRE resulted in early identification of patients at risk for perianal complications.

Cost-utility analysis of pralatrexate for relapsed or refractory peripheral T-cell lymphoma based on a case-matched historical control study along with single arm clinical trial.

BACKGROUND: Patients with relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) treated with pralatrexate have previously shown superior overall survival (OS) compared to those who underwent conventional chemotherapy (CC, 15.4 vs. 4.07 months). We conducted an economic evaluation of pralatrexate from a societal perspective in Korea based on data from the PROPEL phase II study. METHODS: Using a Markov model with a weekly cycle, we simulated the experience of patients with R/R PTCL receiving pralatrexate or CC for 15 years. The model consists of five health states; initial treatment, treatment pause, subsequent treatment, stem cell transplantation (SCT) success, and death. Comparative effectiveness was based on PROPEL phase II single-arm study and its matched historical control analysis. Costs included drug, drug administration, monitoring, adverse event management, and SCT costs. RESULTS: The incremental cost-effectiveness ratio of the base case was $39,153 per quality-adjusted life-year (QALY) gained. The results of one-way sensitivity analysis ranged from $33,949 to $51,846 per QALY gained, which remained within an implicit willingness-to-pay (WTP) threshold of anticancer drugs in Korea. CONCLUSIONS: Pralatrexate is a cost-effective intervention with improved OS and incremental costs within the WTP limit. Pralatrexate could function as a new therapeutic option for patients suffering from life-threatening R/R PTCL.