Uijeongbu St. Mary's Hospital

Lee J.M., Choi K.H., Song Y.B., Lee J., Lee S., Lee S.Y., Kim S.M., Yun K.H., Cho J.Y., Kim C.J., Ahn H., Nam C., Yoon H., Park Y.H., Lee W.S., et. al.

Min S., Kim D.H., Joe D.J., Kim B.W., Jung Y.H., Lee J.H., Lee B., Doh I., An J., Youn Y., Joung B., Yoo C.D., Ahn H., Lee K.J.

AbstractWearable blood‐pressure sensors have recently attracted attention as healthcare devices for continuous non‐invasive arterial pressure (CNAP) monitoring. However, the accuracy of wearable blood‐pressure (BP) monitoring devices has been controversial due to the low signal quality of sensors, the absence of an accurate transfer function to convert the sensor signals into BP values, and the lack of clinical validation regarding measurement precision. Here, a wearable piezoelectric blood‐pressure sensor (WPBPS) is reported, which achieves a high normalized sensitivity (0.062 kPa−1), and fast response time (23 ms) for CNAP monitoring. The transfer function of a linear regression model is designed, offering a simple solution to convert the flexible piezoelectric sensor signals into BP values. In order to verify the measurement accuracy of WPBPS, clinical trials are performed on 35 subjects aged from 20 to 80 s after screening. The mean difference between the WPBPS and a commercial sphygmomanometer of 175 BP data pairs is −0.89 ± 6.19 and −0.32 ± 5.28 mmHg for systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively. By building a WPBPS‐embedded wristwatch, the potentially promising use of a convenient, portable, continuous BP monitoring system for cardiovascular disease diagnosis is demonstrated.

Kario K., Yokoi Y., Okamura K., Fujihara M., Ogoyama Y., Yamamoto E., Urata H., Cho J., Kim C., Choi S., Shinohara K., Mukai Y., Ikemoto T., Nakamura M., Seki S., et. al.

Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (−6.6 mmHg) and sham control (−6.5 mmHg) groups (difference: −0.1, 95% confidence interval −5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: –1.8 mmHg [p = 0.488] and −2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. NCT02918305 ( http://www.clinicaltrials.gov ).

Oh J., Oh B., Lee K., Chae J., Yun K.

Objective: Although distinctive structural abnormalities occur in patients with schizophrenia, detecting schizophrenia with MRI remains challenging. This study aimed to detect schizophrenia in structural MRI data sets using a trained deep learning algorithm. Method: Five public MRI data sets (BrainGluSchi, COBRE, MCICShare, NMorphCH and NUSDAST) from schizophrenia patients and normal subjects were used to train a deep convolutional neural network (a total of 873 structural MRI sets). Results: A deep learning algorithm trained with structural MR images detected schizophrenia in randomly selected images with a reliable performance (AUC of 0.96). It could also find MR images from schizophrenia patients in an untrained data set with an AUC of 0.71 to 0.90. The deep learning algorithm’s classification performance degraded to an AUC of 0.71 when a new data set with younger patients and a shorter duration of illness than the training data sets was presented. The brain regions contributing the most to the performance of the algorithm were the right temporal area, followed by the right parietal area. Semitrained clinical specialists hardly discriminated schizophrenia from healthy controls (AUC: 0.61) in the set of 100 randomly selected brain images. Conclusions: The deep learning algorithm showed good performance for detecting schizophrenia and identified relevant structural features from structural brain MRI data; it had an acceptable classification performance in a separate group of patients at an earlier stage of the disease. Deep learning can be used to delineate structural characteristics of schizophrenia and to provide supplementary information on the diagnosis in clinical settings.

Lee J.M., Kim H.K., Park K.H., Choo E.H., Kim C.J., Lee S.H., Kim M.C., Hong Y.J., Ahn S.G., Doh J., Lee S.Y., Park S.D., Lee H., Kang M.G., Koh J., et. al.

Abstract Aims In patients with acute myocardial infarction (MI) and multivessel coronary artery disease, percutaneous coronary intervention (PCI) of non-infarct-related artery reduces death or MI. However, whether selective PCI guided by fractional flow reserve (FFR) is superior to routine PCI guided by angiography alone is unclear. The current trial sought to compare FFR-guided PCI with angiography-guided PCI for non-infarct-related artery lesions among patients with acute MI and multivessel disease. Methods and results Patients with acute MI and multivessel coronary artery disease who had undergone successful PCI of the infarct-related artery were randomly assigned to either FFR-guided PCI (FFR ≤0.80) or angiography-guided PCI (diameter stenosis of >50%) for non-infarct-related artery lesions. The primary end point was a composite of time to death, MI, or repeat revascularization. A total of 562 patients underwent randomization. Among them, 60.0% underwent immediate PCI for non-infarct-related artery lesions and 40.0% were treated by a staged procedure during the same hospitalization. PCI was performed for non-infarct-related artery in 64.1% in the FFR-guided PCI group and 97.1% in the angiography-guided PCI group, and resulted in significantly fewer stent used in the FFR-guided PCI group (2.2 ± 1.1 vs. 2.5 ± 0.9, P < 0.001). At a median follow-up of 3.5 years (interquartile range: 2.7–4.1 years), the primary end point occurred in 18 patients of 284 patients in the FFR-guided PCI group and in 40 of 278 patients in the angiography-guided PCI group (7.4% vs. 19.7%; hazard ratio, 0.43; 95% confidence interval, 0.25–0.75; P = 0.003). The death occurred in five patients (2.1%) in the FFR-guided PCI group and in 16 patients (8.5%) in the angiography-guided PCI group; MI in seven (2.5%) and 21 (8.9%), respectively; and unplanned revascularization in 10 (4.3%) and 16 (9.0%), respectively. Conclusion In patients with acute MI and multivessel coronary artery disease, a strategy of selective PCI using FFR-guided decision-making was superior to a strategy of routine PCI based on angiographic diameter stenosis for treatment of non-infarct-related artery lesions regarding the risk of death, MI, or repeat revascularization.

Jeon J., Noh H., Lee H., Park H., Ha Y., Park S.H., Lee H., Kim S., Kang H.C., Eyun S., Yang S., Kim Y.

ObjectivesRecently, necroptosis has attracted increasing attention in arthritis research; however, it remains unclear whether its regulation is involved in osteoarthritis (OA) pathogenesis. Since receptor-interacting protein kinase-3 (RIP3) plays a pivotal role in necroptosis and its dysregulation is involved in various pathological processes, we investigated the role of the RIP3 axis in OA pathogenesis.MethodsExperimental OA was induced in wild-type or Rip3 knockout mice by surgery to destabilise the medial meniscus (DMM) or the intra-articular injection of adenovirus carrying a target gene (Ad-Rip3 and Ad-Trim24 shRNA). RIP3 expression was examined in OA cartilage from human patients; Trim24, a negative regulator of RIP3, was identified by microarray and in silico analysis. Connectivity map (CMap) and in silico binding approaches were used to identify RIP3 inhibitors and to examine their direct regulation of RIP3 activation in OA pathogenesis.ResultsRIP3 expression was markedly higher in damaged cartilage from patients with OA than in undamaged cartilage. In the mouse model, adenoviral RIP3 overexpression accelerated cartilage disruption, whereas Rip3 depletion reduced DMM-induced OA pathogenesis. Additionally, TRIM24 knockdown upregulated RIP3 expression; its downregulation promoted OA pathogenesis in knee joint tissues. The CMap approach and in silico binding assay identified AZ-628 as a potent RIP3 inhibitor and demonstrated that it abolished RIP3-mediated OA pathogenesis by inhibiting RIP3 kinase activity.ConclusionsTRIM24-RIP3 axis perturbation promotes OA chronicity by activating RIP3 kinase, suggesting that the therapeutic manipulation of this pathway could provide new avenues for treating OA.

Na H.S., Park J., Cho K., Kwon J.Y., Choi J., Jhun J., Kim S.J., Park S., Cho M.

Osteoarthritis (OA), which is the most common degenerative joint disorder, has been considered a non-inflammatory disease with abnormal mechanics. Interleukin (IL)-17 is a pleiotropic cytokine involved in inflammatory diseases and their production is driven by the cytokine including IL-1 and IL-23. However, little is known about the mechanism of IL-17 in the development of OA. Here, we investigated the role of IL-17 in the pathogenesis of OA using monosodium iodoacetate (MIA)-injected IL-17 and IL-1 receptor antagonist (IL-1Ra) double-deficient mice. In MIA-injected IL-1RaKO mice, nociceptive properties, degree of cartilage damage, and the level of inflammatory factors in articular cartilage were increased compared to MIA-injected wild-type mice. Interestingly, the intestinal architecture was impaired in IL-1RaKO mice compared to wild-type mice and the damage was further exacerbated by MIA injection. Deficiency of IL-17 reduced nociceptive properties and cartilage destruction, as well as inflammation-related factors in MIA-injected IL-1RaKO mice compared to MIA-injected wild-type mice. Furthermore, IL-17-treated chondrocytes from OA patients showed enhanced expression of catabolic factors that are involved in the destruction of cartilage in OA. IL-17 accelerates the destruction of cartilage and small intestine via regulation of several inflammatory mediators in an OA murine model. These results suggest that IL-17 plays a critical role in the development of OA.

Na H.S., Kwon J.Y., Lee S., Lee S.H., Lee A.R., Woo J.S., Jung K., Cho K., Choi J., Lee D.H., Min H., Park S., Kim S.J., Cho M.

Osteoarthritis (OA) is the most common degenerative arthritis associated with pain and cartilage destruction in the elderly; it is known to be involved in inflammation as well. A drug called celecoxib is commonly used in patients with osteoarthritis to control pain. Metformin is used to treat type 2 diabetes but also exhibits regulation of the autophagy pathway. The purpose of this study is to investigate whether metformin can treat monosodium iodoacetate (MIA)-induced OA in rats. Metformin was administered orally every day to rats with OA. Paw-withdrawal latency and threshold were used to assess pain severity. Cartilage damage and pain mediators in dorsal root ganglia were evaluated by histological analysis and a scoring system. Relative mRNA expression was measured by real-time PCR. Metformin reduced the progression of experimental OA and showed both antinociceptive properties and cartilage protection. The combined administration of metformin and celecoxib controlled cartilage damage more effectively than metformin alone. In chondrocytes from OA patients, metformin reduced catabolic factor gene expression and inflammatory cell death factor expression, increased LC3Ⅱb, p62, and LAMP1 expression, and induced an autophagy–lysosome fusion phenotype. We investigated if metformin treatment reduces cartilage damage and inflammatory cell death of chondrocytes. The results suggest the potential for the therapeutic use of metformin in OA patients based on its ability to suppress pain and protect cartilage.

Lee Y.J., Kim J.Y., Jeon S.H., Nam H., Jung J.H., Jeon M., Kim E., Bae S.J., Ahn J., Yoo T., Sun W.Y., Ahn S.G., Jeong J., Park S., Park W.C., et. al.

Despite being a standard treatment option in breast cancer, immune checkpoint inhibitors (ICIs) are only efficacious for a subset of patients. To gain a better understanding of the antitumor immune response in breast cancer, we examined the heterogeneity of CD8 + T cells in tumors, metastatic lymph nodes (mLNs), and peripheral blood from patients with early breast cancer ( n  = 131). Among tissue-resident memory CD8 + T (T RM ) cells, including virus- and tumor-specific CD8 + T cells, CD39 expression was observed in a tumor-specific and exhausted subpopulation in both tumors and mLNs. CD39 + T RM cells from tumors and mLNs exhibited a phenotypic similarity and clonally overlapped with each other. Moreover, tumor or mLN CD39 + T RM cells clonally overlapped with CD39 − T RM and non-T RM cells in the same compartment, implying a tissue-specific differentiation process. These inter-subpopulationally overlapping CD39 + T RM clonotypes were frequently detected among effector memory CD8 + T cells in peripheral blood, suggesting a systemic clonal overlap. CD39 + T RM cell enrichment was heterogeneous among molecular subtypes of breast cancer, which is associated with the different role of antitumor immune responses in each subtype. In vitro blockade of PD-1 and/or CTLA-4 effectively restored proliferation of CD39 + T RM cells and enhanced cytokine production by CD8 + T cells from tumors or mLNs, particularly in the presence of CD39 + T RM enrichment. This suggests that CD39 + T RM cells have a capacity for functional restoration upon ICI treatment. Thus, our study indicates that CD39 + T RM cells with a clonal overlap across compartments are key players in antitumor immunity in breast cancer.

Chang D., Park J., Baek G.H., Kim H.J., Bosco A., Hey H.W., Lee C.

There have not been well-designed survey studies investigating the impact of the coronavirus disease 2019 (COVID-19) pandemic on orthopaedic resident education. A 58-question, web-based survey was administered to orthopaedic residents in South Korea. A total of 229 orthopaedic residents from 43 hospitals completed the survey questionnaire. The average working time of 72.7 hours/week before the pandemic was decreased to 65.6 hours/week during the pandemic (p < 0.001). The time working in the operating room was significantly decreased during the pandemic, but not in the emergency centre and outpatient clinic. The education times for lecture and clinical case discussion were decreased during the pandemic (both, p < 0.001), respectively. While the use of traditional teaching methods was decreased, the use of online-based teaching methods was increased (p < 0.001). However, satisfaction level with online-based teaching methods was significantly lower compared with that of traditional teaching methods. The average working time exposed to the patients with COVID-19 was 9.7 hours/week. About 47.6% of orthopaedic residents experienced isolation or quarantine. The average score for quality of life, which was 68.9 out of 100 scores before the pandemic, decreased to 61.7 during the pandemic (p < 0.001). The most stressful factor for orthopaedic residents during the pandemic was family/relative health, followed by their own health and residency program. The COVID-19 pandemic had a significant impact on orthopaedic resident education in South Korea. Therefore, flexible and sustainable strategies are necessary to prepare for the future as well as the current pandemic situation.