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Digital therapeutics are defined as “deliver evidence-based therapeutic interventions to patients which are driven by high-quality software programs to prevent, manage, or treat medical conditions.” Advances in information and communication technology, artificial intelligence, big data, and digital therapeutics are attracting attention in the healthcare market. Limited access to medical care due to the global epidemic of COVID-19 and the increasing demand for medical care from chronic disease patients owing to the aging of the population have facilitated the expansion of interest in digital health care. As the market size grows, there are currently more than 60 digital therapeutics that have been approved by US Food and Drug Administration, but digital therapeutics are still at an early stage in the market that is not fully established. In this article, we will briefly review the outline of digital therapeutics, the current landscape, future perspectives, and applications of digital therapeutics in the field of otolaryngology.
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BACKGROUND@#Biodegradable poly (l-lactic acid) (PLLA), a bio safe polymer with a large elastic modulus, is widely used in biodegradable medical devices. However, because of its poor mechanical properties, a PLLA strut must be made twice as thick as a metal strut for adequate blood vessel support. Therefore, the mechanical properties of a drug-eluting metal-based stents (MBS) and a bioresorbable vascular scaffolds (BVS) were evaluated and their safety and efficacy were examined via a long-term rabbit iliac artery model. @*METHODS@#The surface morphologies of the MBSs and BVSs were investigated via optical and scanning electron microscopy. An everolimus-eluting (EE) BVS or an EE-MBS was implanted into rabbit iliac arteries at a 1.1:1 stent-toartery ratio. Twelve months afterward, stented iliac arteries from each group were analyzed via X-ray angiography, optical coherence tomography (OCT), and histopathologic evaluation. @*RESULTS@#Surface morphology analysis of the EE coating on the MBS confirmed that it was uniform and very thin (4.7 lm). Comparison of the mechanical properties of the EE-MBS and EE-BVS showed that the latter outperformed the former in all aspects (radial force (2.75 vs. 0.162 N/mm), foreshortening (0.24% vs. 1.9%), flexibility (0.52 vs. 0.19 N), and recoil (3.2% vs. 6.3%). At all time points, the percent area restenosis was increased in the EE-BVS group compared to the EE-MBS group. The OCT and histopathological analyses indicate no significant changes in strut thickness. @*CONCLUSION@#BVSs with thinner struts and shorter resorption times should be developed. A comparable long-term safety/efficacy evaluation after complete absorption of BVSs should be conducted.
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When restoring with a dental digital system for implant-supported prosthesis, a double digital scanning technique is required: an intraoral scan of the three-dimensional implant location and intraoral scan after placement of temporary denture or provisional prosthesis. During the intraoral scan, the use of scan body as a stable landmark can improve the accuracy of digital impression and simplify laboratory process. In this case, a full-digital system was used to plan and fabricate a custom abutment, provisional prosthesis, and definitive prosthesis. After implant placement, the scan area of the intraoral scan body connected with implant and the intraoral scan body marked on the inside of temporary denture were superimposed. Out of the superimposed files, a custom abutment and provisional prosthesis were fabricated which match the vertical dimension of temporary denture, and definitive prosthesis was fabricated based on provisional prosthesis. We report this case because result has been functionally and esthetically satisfactory by using vertical dimension and central relation set during the fabrication of temporary denture to the definitive prosthesis.
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The most important aspect of the imaging role for indeterminate bile duct stricture is to make a differential diagnosis on whether the stricture is highly likely to be malignant or benign. Compared to benign stricture, malignant stricture is longer, thicker, and has indistinct outer border and irregularity of the lumen in contrastenhanced computed tomography and magnetic resonance (MR). Also, in the contrast-enhanced portal phase, malignant stricture has a stronger enhancement than the liver parenchyma. There are studies to differentiate between malignant and benign stricture in diffusion weighted image, a functional MR image, but there remains controversial. Sometimes, malignant biliary stricture may be caused by bile duct invasion of gallbladder cancer, pancreatic cancer, hepatocellular carcinoma, biliary metastasis, and lymphoma. Among the potential causes of indeterminate biliary stricture, the characteristics of multifocal biliary stricture mainly suggest benign sclerosing cholangitis, and various external compression factors that cause biliary stricture can be differentiated by radiologic imaging. There are causes of biliary dilatation without obstructive lesion, radiologic diagnosis can be made by considering various characteristics.
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Objective@#Coronavirus disease 2019 (COVID-19) pandemic has been affecting the safety of hospital healthcare workers and the outcome of out-of-hospital cardiac arrest patients. This study aimed to analyze the influence of the changes inhospital infection control protocols (ICP) and cardiopulmonary resuscitation (CPR) environment on the treatment outcomes of out-of-hospital cardiac arrest patients. @*Methods@#The medical records of patients who visited the emergency room were retrospectively reviewed for the period from March 13, 2019 to March 13, 2021. Patient data were analyzed before and after March 13, 2020, when the “in-hospital CPR guidelines related to COVID-19 infection” was recommended by the Korean Society of Emergency Medicine. We performed a comparison and analysis of the first epinephrine administration time and the intubation time with other CPR-related factors in both groups. The in-hospital return of spontaneous circulation (ROSC) and the over 24-hour survival rate were defined as treatment outcomes. @*Results@#A total number of 453 patients were included in the study. After ICP, the in-hospital ROSC was increased (29.8% vs. 42.1%, P=0.006), whereas the over 24-hour survival rate was decreased (67.2% vs. 40.6%, P=0.001). The time intervals from the hospital visit to the first epinephrine administration—1.0 (0-1.0) vs. 1.0 (0-2.0), P=0.007—and tracheal intubation—1.0 (0-1.0) vs. 1.0 (1.0-2.8), P<0.001—were statistically significantly higher than those before ICP application. In our multivariable analysis, the ICP application and pre-hospital emergency medical service (EMS) response time were factors associated with the treatment outcome. @*Conclusion@#After the application of the ICP, both the first epinephrine administration time and the tracheal intubation time from the patient’s hospital visit were prolonged. The application of ICP and the delayed EMS response time were factors associated with the treatment outcome.
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Owing to the paucity of information on the clinical outcomes in female patients with acute myocardial infarction (AMI) in relation to the comorbid disease burden, we explored the differences in their clinical outcomes and identified predictive indicators.A total of 3,419 female AMI patients were stratified into two groups: Group A (those with zero or one comorbid diseases) (n=1,983) and Group B (those with two to five comorbid diseases) (n=1,436). Five comorbid conditions were considered: hypertension, diabetes mellitus, dyslipidemia, prior coronary artery disease, and prior cerebrovascular accidents. The primary outcome was major adverse cardiac and cerebrovascular events (MACCEs). The incidence of MACCEs was higher in Group B than in Group A in both the unadjusted and propensity score-matched data. Among the comorbid conditions, hypertension, diabetes mellitus, and prior coronary artery disease were found to be independently associated with an increased incidence of MACCEs. Higher comorbid disease burden was positively associated with adverse outcomes in the female population with AMI. Since both hypertension and diabetes mellitus are modifiable and independent predictors of adverse outcomes after AMI, it may be necessary to focus on the optimal management of blood pressure and glucose levels to improve cardiovascular outcomes.
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Lactase non-persistence (LNP), one of the causes of lactose intolerance, is related to lactase gene associated single nucleotide polymorphisms (SNPs). Since the frequency of LNP varies by ethnic group and country, the research to reveal the presence or absence of LNP for specific people has been conducted worldwide. However, in East Asia, the study of lactase gene associated SNPs have not been sufficiently examined so far using ancient human specimens from archaeological sites. In our study of Joseon period human remains (n=14), we successfully revealed genetic information of lactase gene associated SNPs (rs1679771596, rs41525747, rs4988236, rs4988235, rs41380347, rs869051967, rs145946881 and rs182549), further confirming that as for eight SNPs, the pre-modern Korean people had a lactase non-persistent genotype. Our report contributes to the establishment of LNP associated SNP analysis technique that can be useful in forthcoming studies on human bones and mummy samples from East Asian archaeological sites.
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Desmoid fibromatosis is a very slowly growing benign fibroblast tumor. Locally aggressive and non-metastasizing, it is a well-differentiated, unencapsulated monoclonal myofibroblastic proliferation that has a tendency for local invasion and recurrence. About 15% of all desmoidtype fibromatosis develops within the head and neck. The majority of head and neck desmoid tumor is located in the neck, but less frequently in the face, scalp, oral cavity, mandible, paranasal sinuses, orbit, ear and other structures. We report a very rare case in a 55-year-old female of a desmoid fibromatosis arising from the lateral nasal wall of anterior portion of uncinated process. We discuss the clinicopathologic features and successful treatment of nasal desmoid tumor with a literature review.
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Objectives@#: In this study, we evaluate psychological stress, symptoms of anxiety and depressed mood and resilience which medical residents and interns perceived during COVID-19 event, then investigate the associations between stress and the symptoms and mediating effect of resilience on the associations. @*Methods@#: In this study, we made a self-reporting form to evaluate psychological stress with perceived stress scale (PSS), symptoms of anxiety and depressed mood with Hospital anxiety and depression scale (HAD), and resilience with Conner-Davidson Resilience Scale (CD-RISC). Medical residents and interns, who worked in a hospital during COVID-19 event, filled the self-reporting forms from july, 2020 to august, 2020. We conducted a Pearson correlation coefficient and a multiple regression to confirm association between psychological stress and symptoms of anxiety and depressed mood, then mediating effect of resilience. @*Results@#: The higher stress perceived, the more symptoms of anxiety and depressed mood were reported by medical residents and interns. The higher resilience is associated with lower stress and less symptoms of anxiety and depressed mood, which resilience is proven to mediate partially the association between stress and symptoms of depressed mood. @*Conclusions@#: This study shows that resilience has a partial mediating effects on the association between stress and psychological pathology especially depressed mood, given that medical residents and interns were under psychological distress during COVID-19 event. This suggests that resilience is the key for medical trainees to overcome the future crisis like COVID-19 event.
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Objectives@#：This study was conducted to investigate the effect of 1-year administration of second-generation antipsychotics (SGAs) on the platelet activity in patients with schizophrenia through a retrospective review of the medical records. @*Methods@#：The mean platelet component (MPC) value was used as an index of the platelet activity. The included subjects (N=24) were the patients who were confirmed to have taken SGAs continuously for one year after the first MPC measurement had been performed. The change of MPC was verified through a paired sample t-test. @*Results@#：The result revealed that the mean MPC value was significantly decreased from 26.5±1.4 g/dL to 25.6±1.8 g/dL after 1-year administration of SGAs from the time of the first MPC measurement. @*Conclusions@#：This study suggests that 1-year administration of SGAs may be related with increased platelet activity, and that close monitoring for risks such as cerebrovascular/cardiovascular or thromboembolic diseases may be necessary during SGAs treatment in clinical practice.
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A three-dimensional (3D) segmentation and model reconstruction is a specialized tool to reveal spatial interrelationship between multiple internal organs by generating images without overlapping structures. This technique can also be applicable to mummy studies, but related reports have so far been very rare. In this study, we applied 3D segmentation and model reconstruction to computed tomography images of a Korean mummy with congenital diaphragmatic hernia. As originally revealed by the autopsy in 2013, the current 3D reconstruction reveals that the mummy’s heart is shifted to the left due to the liver pushing up to thoracic cavity thorough diaphragmatic hernial defect. We can generate 3D images by calling up the data exclusively from mummy’s target organs, thus minimizing the confusion of diagnosis that could be caused by overlapping organs.
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Background/Aims@#Little is known about the clinical characteristics and treatment outcomes of ST-segment elevation myocardial infarction (STEMI) in Korea during the coronavirus disease 2019 (COVID-19) era. We aimed to evaluate the clinical characteristics and treatment outcomes of patients with STEMI in the COVID-19 era. @*Methods@#A total of 588 consecutive patients with STEMI who underwent primary percutaneous coronary intervention were included in this study. The patients were categorized into the COVID-19 (from January 20, 2020 to December 31, 2020) and control groups (from January 20, 2019 to December 31, 2019). @*Results@#The COVID-19 group showed pre-hospital and in-hospital delays than the control group. The control group underwent more thrombus aspiration and had a higher proportion of left main coronary artery diseases, while the COVID-19 group had a higher proportion of multivessel diseases with a marked increase in the number and total length of stents than the control group. As for the prescribed medications, the COVID-19 group was administered more beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins than the control group. The clinical outcomes were comparable between the groups, except for higher incidences of atrioventricular block and temporary pacemaker implantation in the COVID-19 group. @*Conclusions@#Reperfusion after STEMI treatment during the COVID-19 period was delayed; therefore, efforts should be made to improve on reperfusion.
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Laryngotracheal separation (LTS) is one of the treatment options for intractable aspiration. Here, we present two cases of LTS with successful prevention of intractable aspiration.The first case was a 60-year-old man with severe hypoxic brain damage caused by hydrogen sulfide (H2S) intoxication; he was admitted to our department for comprehensive rehabilitation. Frequent tracheal suction was required due to the excess secretion from saliva aspiration. Matters were complicated when he suffered frequent regurgitation and vomiting, which was followed by tracheal aspiration. In the second case, a 78-year-old man presented with a severe traumatic brain injury. He had experienced recurrent aspiration pneumonia, which was unresponsive to conventional therapy. In both cases, LTS was performed to prevent intractable aspiration pneumonia. Subsequent to the LTS procedure, videofluoroscopic swallowing study showed complete prevention of the aspiration in both patients. Moreover, tracheal secretion was reduced, and tracheal suction was no longer required. Post-surgery, there was no development of aspiration pneumonia during their hospital stays.
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Background/Aims@#Rapid percutaneous coronary intervention (PCI) is the cornerstone of treatment for ST-elevation myocardial infarction (STEMI). However, there have been conflicting results regarding the differences in clinical outcomes between on-hours and off-hours presentation in STEMI patients. We aimed to examine the difference in long-term outcomes between off-hours and on-hours PCI in patients with STEMI. @*Methods@#The characteristics and clinical outcomes of 5,364 STEMI patients between November 2011 and June 2015 from the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) registry were analyzed. Patients were divided into two groups: the off-hours group (weekdays from 6:01 PM to 7:59 AM, weekends, and legal holidays) and the on-hours group (weekdays from 8:00 AM to 6:00 PM). Major adverse cardiac and cerebrovascular events (MACCEs) were defined as a composite of allcause mortality, non-fatal myocardial infarction, any revascularization, cerebrovascular accident, and stent thrombosis. The primary endpoint was the occurrence of MACCEs, and all other clinical outcomes were analyzed. @*Results@#A total of 3,119 patients (58.1%) underwent primary PCI due to STEMI during off-hours and 2,245 patients (41.9%) during on-hours. At 36 months, the clinical outcomes of the off-hours group were similar to those of the on-hours group in both the unadjusted and propensity score weighting-adjusted analyses. @*Conclusions@#Our analysis revealed that the long-term outcomes in STEMI patients admitted to hospitals during off-hours were similar to outcomes of those admitted during on-hours.
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Background/Aims@#Acute myocardial infarction (AMI) is conventionally recognized as an urgent medical condition requiring timely and effective reperfusion therapy. However, the results of studies on the clinical outcomes in AMI according to hospital visit timings are inconclusive. To explore the difference in long-term outcomes between off- and on-hour percutaneous coronary interventions (PCI) in patients with AMI of Killip functional classification III–IV (Killip III–IV AMI). @*Methods@#Data on the characteristics and clinical outcomes of 1,751 patients with Killip III–IV AMI between November 2011 and June 2015 from the Korea Acute Myocardial Infarction Registry-National Institutes of Health registry were analyzed. All participants were allocated into two groups: off-hour (weekdays from 6:00 PM to 8:00 AM, weekends, and legal holidays) and on-hour (weekdays from 8:00 AM to 6:00 PM) groups. The incidence of major adverse cardiac and cerebrovascular events, defined as a composite of all-cause mortality, nonfatal myocardial infarction, any revascularization, cerebrovascular accident, and stent thrombosis, was the primary endpoint. @*Results@#Among the 1,751 patients, 572 (39.1%) underwent PCI during on-hours and 892 (60.9%) during off-hours. At the 3-year follow-up, no significant difference was found in the clinical outcomes between the two groups in both the unadjusted and propensity-score weighing-adjusted analyses. @*Conclusions@#The outcomes of patients with Killip III–IV AMI admitted during off- and on-hours were similar.
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Purpose@#Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC. @*Materials and Methods@#We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments. @*Results@#In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug. @*Conclusion@#This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.
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Although research conducted in East Asia has uncovered parasite eggs from ancient toilets or cesspits, data accumulated to date needs to be supplemented by more archaeoparasitological studies. We examined a total of 21 soil samples from a toilet-like structure at the Hwajisan site, a Baekje-period royal villa, in present-day Korea. At least 4 species of helminth eggs, i.e., Trichuris trichiura, Ascaris lumbricoides, Clonorchis sinensis, and Trichuris sp. (or Trichuris vulpis) were detected in 3 sediment samples of the structure that was likely a toilet used by Baekje nobles. The eggs of T. trichiura were found in all 3 samples (no. 1, 4, and 5); and A. lumbricoides eggs were detected in 2 samples (no. 4 and 5). C. sinensis and T. vulpis-like eggs were found in no. 5 sample. From the findings of this study, we can suppose that the soil-transmitted helminths were prevalent in ancient Korean people, including the nobles of Baekje Kingdom during the 5th to 7th century.
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Our previous research on coprolite specimens from the mummies of Joseon Dynasty (1392-1910 CE) has revealed various species of parasite eggs. Herein, we added 2 new helminthic cases of human remains from Joseon-period graves in the Republic of Korea (Korea). The organic materials precipitated on the hip bones of 2 half-mummied cases (Goryeong and Gwangmyeong cases) were collected, rehydrated, and examined by a microscope. In the sample from Goryeong-gun (gun=County), ova of Trichuris trichiura, Clonorchis sinensis, and Metagonimus spp. were detected, and eggs of T. trichiura and A. lumbricoides were found from the sample of Gwangmyeong-si (si=City). By adding this outcome to the existing data pool, we confirm our previous estimates of Joseon-period parasite infection rates. The overall rates of A. lumbricoides, T. trichiura, and C. sinensis decreased dramatically from Joseon to the modern period. In Goryeong mummy specimen, we also found Metagonimus spp. eggs that has rarely been detected in archaeological samples so far.
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Background/Aims@#High-sensitivity cardiac troponin (hs-TnT) assays detect very low levels of cardiac troponin. This study examined the interval change between initial and subsequent hs-TnT levels and evaluated its ability to predict significant coronary stenosis. @*Methods@#The study analyzed 163 patients who presented with acute coronary syndrome (ACS) and underwent coronary angiography (CAG) between April 2014 and May 2018. The 0 and 3-hour hs-TnT were checked. The patients were subdivided into positive (n = 32) and negative (n = 131) interval change groups. The presence of significant coronary artery stenosis on CAG in the two groups was compared. @*Results@#The positive interval change group was older and had higher 0 and 3-hour hs-TnT and blood glucose levels than the negative interval change group. Significant coronary stenosis was more common in the positive interval change group than in the negative interval change group (68.8% vs. 23.7%, p = 0.001). However, vasospasm was more common in the negative interval change group (6.3% vs. 31.3%, p = 0.003). The positive interval change group had higher rates of bifurcation lesions and received more percutaneous coronary intervention. In multivariate analysis, age, interval change of serial hs-TnT and diabetes mellitus were independent predictors of significant coronary artery stenosis. @*Conclusions@#This study identified a relationship between the serial change in cardiac biomarkers and the presence of significant coronary stenosis in patients with ACS. Serial hs-TnT change was associated with real angiographic stenosis in patients with ACS.
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Purpose@#The soluble form programmed death-ligand 1 (sPDL1) has immunosuppressive properties and is being studied as a candidate biomarker for immuno-oncology drug development. We measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC). @*Materials and Methods@#We prospectively enrolled 68 GC patients who were candidates for palliative standard first-line chemotherapy, and serially collected blood at baseline and after one cycle of chemotherapy, at the best response and after disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progressionfree survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off value of sPDL1 levels for survival analysis was found using C-statistics. @*Results@#The median baseline sPDL1 was 0.8 ng/mL (range, 0.06 to 6.06 ng/mL). The median OS and PFS were 14.9 months and 8.0 months, respectively. sPDL1 and NLR showed a weak positive correlation (Spearman’s rho=0.301, p=0.013). Patients with low levels of sPDL1 at diagnosis (< 1.92 ng/mL) showed a better OS and PFS than patients with a high sPDL1. The baseline sPDL1 before treatment was higher in the progressive disease group than in the stable disease and partial response groups. Patients whose sPDL1 increased after the first cycle of chemotherapy showed worse PFS and OS. Following disease progression, sPDL1 increased compared with the baseline. @*Conclusion@#sPDL1 at prechemotherapy confers a prognostic value for PFS and OS in GC patients under palliative first-line chemotherapy. Dynamics of sPDL1 during chemotherapy correlates with disease progression.