1.Current Concepts and Medical Management for Patients with Radiographic Axial Spondyloarthritis
Seung-Hoon BAEK ; Seungbae OH ; Bum-Jin SHIM ; Jeong Joon YOO ; Jung-Mo HWANG ; Tae-Young KIM ; Seung-Cheol SHIM
Hip & Pelvis 2024;36(4):234-249
Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL23/IL17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigenB27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.
2.Current Concepts and Medical Management for Patients with Radiographic Axial Spondyloarthritis
Seung-Hoon BAEK ; Seungbae OH ; Bum-Jin SHIM ; Jeong Joon YOO ; Jung-Mo HWANG ; Tae-Young KIM ; Seung-Cheol SHIM
Hip & Pelvis 2024;36(4):234-249
Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL23/IL17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigenB27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.
3.Current Concepts and Medical Management for Patients with Radiographic Axial Spondyloarthritis
Seung-Hoon BAEK ; Seungbae OH ; Bum-Jin SHIM ; Jeong Joon YOO ; Jung-Mo HWANG ; Tae-Young KIM ; Seung-Cheol SHIM
Hip & Pelvis 2024;36(4):234-249
Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL23/IL17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigenB27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.
4.Tissue-Engineered Bone Regeneration for Medium-to-Large Osteonecrosis of the Femoral Head in the Weight-Bearing Portion:An Observational Study
Eui-Kyun PARK ; Bum-Jin SHIM ; Suk-Young KIM ; Seung-Hoon BAEK ; Shin-Yoon KIM
Clinics in Orthopedic Surgery 2024;16(5):702-710
Background:
Stem cell therapy for the treatment of osteonecrosis of the femoral head (ONFH) showed promising outcomes. However, ONFH with a large lesion in the weight-bearing portion is a poor prognostic factor and still challenging issue to be solved. We aimed to evaluate the effect of tissue-engineered bone regeneration for this challenging condition to preserve the femoral head.
Methods:
A total of 7 patients (9 hips) with ONFH who received osteoblasts expanded ex vivo from bone marrow-derived mesenchymal stem cells (BMdMSCs) and calcium metaphosphate (CMP) as scaffolds from March 2002 to March 2004 were retrospectively reviewed. The median age was 27.0 years (interquartile range [IQR], 23.0–34.0 years), and the median follow-up period was 20.0 years (IQR, 11.0–20.0 years). After culture and expansion of stem cells, we performed core decompression with BMdMSC implantation at a median number of 10.1 ×107 (IQR, 9.9–10.9 ×107 ). To evaluate radiographic outcomes, the Association Research Circulation Osseous (ARCO) classifications, the Japanese Investigation Committee (JIC) classification, and modified Kerboul combined necrotic angle (mKCNA) were evaluated preoperatively and during follow-up. Clinical outcomes were evaluated by a visual analog scale (VAS) and Harris Hip Score (HHS).
Results:
The preoperative stage of ONFH was ARCO 2 in 5 hips and ARCO 3a in 4 hips. The ARCO staging was maintained in 3 hips of ARCO 2 and 4 hips of ARCO 3a. Two hips of ARCO 2 with radiographic progression underwent total hip arthroplasty. According to mKCNA, 2 hips showed medium lesions, and 7 hips showed large lesions. The size of necrotic lesion was decreased in 4 hips (2 were ARCO 2 and 2 were ARCO 3a). There were no significant changes in JIC classification in all hips (type C1: 3 hips and type C2: 6 hips) (p = 0.655). Clinically, there were no significant changes in the VAS and HHS between preoperative and last followup (p = 0.072 and p = 0.635, respectively).
Conclusions
Tissue engineering technique using osteoblasts expanded ex vivo from BMdMSC and CMP showed promising outcomes for the treatment of pre-collapsed and early-collapsed stage ONFH with medium-to-large size, mainly located in weightbearing areas.
5.Implantation of Culture-Expanded Bone Marrow Derived Mesenchymal Stromal Cells for Treatment of Osteonecrosis of the Femoral Head
Seong-Dae YOON ; Bum-Jin SHIM ; Seung-Hoon BAEK ; Shin-Yoon KIM
Tissue Engineering and Regenerative Medicine 2024;21(6):929-941
BACKGROUND:
Although core decompression (CD) with stem cell for the treatment of osteonecrosis of the femoral head (ONFH) showed promising results in many reports, the efficacy remains uncertain. We aimed to evaluate the efficacy of CD with culture-expanded autologous bone marrow-derived mesenchymal stem cell (BM-MSC) implantation in early stage ONFH.
METHODS:
A total of 18 patients (22 hips) with ONFH who underwent CD with culture-expanded BM-MSC implantation from September 2013 to July 2020 were retrospectively reviewed. The median age was 35.0 years [interquartile range (IQR), 28.5–42.0], and the median follow-up period was 4.0 years (IQR, 2.0–5.3). The median number of MSCs was 1.06 x 108 . To evaluate radiographic and clinical outcomes, Association Research Circulation Osseous (ARCO) classifications, Japanese Investigation Committee classification, combined necrotic angle (CNA) visual analogue scale (VAS) and Harris Hip Score (HHS) were checked at each follow-up.
RESULTS:
The preoperative stage of ONFH was ARCO 2 in 14 hips and ARCO 3a in 8 hips. The ARCO staging was maintained in 7 hips in ARCO 2 and 4 hips in ARCO 3a. The radiographic failure rate of ARCO 2 and 3a was 14.3 and 50%, respectively. Furthermore, CNA decreased to more than 20° in 6 hips (four were ARCO 2 and two were ARCO 3a).There was no significant difference in the VAS and HHS (P = 0.052 and P = 0.535, respectively). Total hip arthroplasty was performed in 4 hips.
CONCLUSION
CD with culture-expanded autologous BM-MSCs showed promising results for the treatment of early stage ONFH.
6.Breast Tissue Reconstruction Using Polycaprolactone Ball Scaffolds in a Partial Mastectomy Pig Model
Kyu-Sik SHIM ; Da Hye RYU ; Han-Saem JO ; Ki-Bum KIM ; Do-Hyun KIM ; Yong-Kyu PARK ; Min HEO ; Hee-Eun CHO ; Eul-Sik YOON ; Won Jai LEE ; Tai Suk ROH ; Seung Yong SONG ; Wooyeol BAEK
Tissue Engineering and Regenerative Medicine 2023;20(4):607-619
BACKGROUND:
Breast cancer patients suffer from lowered quality of life (QoL) after surgery. Breast conservancy surgery (BCS) such as partial mastectomy is being practiced and studied as an alternative to solve this problem. This study confirmed breast tissue reconstruction in a pig model by fabricating a 3-dimensional (3D) printed Polycaprolactone spherical scaffold (PCL ball) to fit the tissue resected after partial mastectomy.
METHODS:
A 3D printed Polycaprolactone spherical scaffold with a structure that can help adipose tissue regeneration was produced using computer-aided design (CAD). A physical property test was conducted for optimization. In order to enhance biocompatibility, collagen coating was applied and a comparative study was conducted for 3 months in a partial mastectomy pig model.
RESULTS:
In order to identify adipose tissue and fibroglandular tissue, which mainly constitute breast tissue, the degree of adipose tissue and collagen regeneration was confirmed in a pig model after 3 months. As a result, it was confirmed that a lot of adipose tissue was regenerated in the PCL ball, whereas more collagen was regenerated in the collagen-coated Polycaprolactone spherical scaffold (PCL–COL ball). In addition, as a result of confirming the expression levels of TNF-a and IL-6, it was confirmed that PCL ball showed higher levels than PCL–COL ball.
CONCLUSION
Through this study, we were able to confirm the regeneration of adipose tissue through a 3-dimensional structure in a pig model. Studies were conducted on medium and large-sized animal models for the final purpose of clinical use and reconstruction of human breast tissue, and the possibility was confirmed.
7.Survival impact of adherence to tyrosine kinase inhibitor in chronic myeloid leukemia
Yundeok KIM ; Tae-Hwa GO ; Jaeyeon JANG ; Jii Bum LEE ; Seung Taek LIM ; Kwang Yong SHIM ; Jong In LEE ; Jee Hyun KONG
The Korean Journal of Internal Medicine 2021;36(6):1450-1458
Background/Aims:
Adherence to tyrosine kinase inhibitors (TKIs) has become a critical aspect of care in chronic myeloid leukemia (CML). We aimed to examine the association of TKI adherence with overall survival (OS) outcomes in Korean patients diagnosed with CML and treated with TKIs using data from the National Health Information Database.
Methods:
This study included 2,870 CML patients diagnosed between 2005 and 2013. Drug adherence was evaluated according to the medication possession ratio (MPR) and classified as high adherence (i.e., MPR ≥ 0.95 [upper 50%]), moderate adherence (i.e., MPR ≥ 0.68 and < 0.95 [middle 25%]), and low adherence (i.e., MPR < 0.68 [lower 25%]).
Results:
The median MPR was 0.95 (range, 0 to 4.67). Male sex (p = 0.003), age < 70 years (p < 0.001), high income (≥ 30%, p < 0.001), and maintaining frontline TKI (< 0.001) were associated with better adherence. Adherence to dasatinib was the lowest (vs. imatinib or nilotinib, p < 0.001). Compared with high MPR patients, those with moderate MPR (hazard ratio [HR], 4.90; 95% confidence interval [CI], 3.87 to 6.19; p < 0.001) and low MPR (HR, 11.6; 95% CI, 9.35 to 14.42; p < 0.001) had poorer OS.
Conclusions
Adherence to TKI treatment is an important factor predicting survival outcomes in Korean CML patients. Male sex, age < 70 years, high income, and maintaining frontline TKI are associated with high adherence to TKI. Thus, those without these characteristics should be closely monitored for treatment adherence.
8.Panel-Reactive and Donor-Specific Antibodies before Lung Transplantation can Affect Outcomes in Korean Patients Receiving Lung Transplantation
Sung Woo MOON ; Moo Suk PARK ; Jin Gu LEE ; Hyo Chae PAIK ; Young Tae KIM ; Hyun Joo LEE ; Samina PARK ; Sun Mi CHOI ; Do Hyung KIM ; Woo Hyun CHO ; Hye Ju YEO ; Seung-il PARK ; Se Hoon CHOI ; Sang-Bum HONG ; Tae Sun SHIM ; Kyung-Wook JO ; Kyeongman JEON ; Byeong-Ho JEONG ; Song Yee KIM ;
Yonsei Medical Journal 2020;61(7):606-613
Purpose:
Data on the distribution and impact of panel reactive antibodies (PRA) and donor specific antibodies (DSA) before lung transplantation in Asia, especially multi-center-based data, are limited. This study evaluated the prevalence of and effects of PRA and DSA levels before lung transplantations on outcomes in Korean patients using nationwide multicenter registry data.
Materials and Methods:
This study included 103 patients who received a lung transplant at five tertiary hospitals in South Korea between March 2015 and December 2017. Mortality, primary graft dysfunction (PGD), and bronchiolitis obliterans syndrome (BOS) were evaluated.
Results:
Sixteen patients had class I and/or class II PRAs exceeding 50%. Ten patients (9.7%) had DSAs with a mean fluorescence intensity (MFI) higher than 1000, six of whom had antibodies with a high MFI (≥2000). DSAs with high MFIs were more frequently observed in patients with high-grade PGD (≥2) than in those with no or low-grade (≤1) PGD. In the 47 patients who survived for longer than 9 months and were evaluated for BOS after the transplant, BOS was not related to DSA or PRA levels. One-year mortality was more strongly related to PRA class I exceeding 50% than that under 50% (0% vs. 16.7%, p=0.007).
Conclusion
Preoperative DSAs and PRAs are related to worse outcomes after lung transplantation. DSAs and PRAs should be considered when selecting lung transplant recipients, and recipients who have preoperative DSAs with high MFI values and high PRA levels should be monitored closely after lung transplantation.
9.Infections in Lung Transplant Recipients during and after Prophylaxis
Moonsuk BAE ; Sang-Oh LEE ; Kyung-Wook JO ; Sehoon CHOI ; Jina LEE ; Eun Jin CHAE ; Kyung-Hyun DO ; Dae-Kee CHOI ; In-Cheol CHOI ; Sang-Bum HONG ; Tae Sun SHIM ; Hyeong Ryul KIM ; Dong Kwan KIM ; Seung-Il PARK
Infection and Chemotherapy 2020;52(4):600-610
Background:
The timeline of infections after lung transplantation has been changed with the introduction of new immunosuppressants and prophylaxis strategies. The study aimed to investigate the epidemiological characteristics of infectious diseases after lung transplantation in the current era.
Materials and Methods:
All patients who underwent lung or heart–lung transplantation at our institution between October 29, 2008 and April 3, 2019 were enrolled. We retrospectively reviewed the patients' medical records till April 2, 2020.
Results:
In total, 100 consecutive lung transplant recipients were enrolled. The median follow-up period was 28 months after lung transplantation. A total of 127 post–lung transplantation bacterial infections occurred. Catheter-related bloodstream infection (25/84, 29.8%) was the most common within 6 months and pneumonia (23/43, 53.5%) was the most common after 6 months. Most episodes (35/40, 87.5%) of respiratory viral infections occurred after 6 months, mainly as upper respiratory infections. The remaining episodes (5/40, 12.5%) mostly manifested as lower respiratory tract infections. Seventy cytomegalovirus infections observed in 43 patients were divided into 23 episodes occurring before and 47 episodes occurring after discontinuing prophylaxis. Of 10 episodes of cytomegalovirus disease, four occurred during prophylaxis and six occurred after prophylaxis.Of 23 episodes of post–lung transplantation fungal infection, 7 were aspergillosis and all occurred after the discontinuation of prophylaxis.
Conclusion
Lung transplant recipients experienced a high burden of infection even after 6 months, especially after the end of the prophylaxis period. Therefore, these patients should be continued to be monitored long-term for infectious disease.
10.Infections in Lung Transplant Recipients during and after Prophylaxis
Moonsuk BAE ; Sang-Oh LEE ; Kyung-Wook JO ; Sehoon CHOI ; Jina LEE ; Eun Jin CHAE ; Kyung-Hyun DO ; Dae-Kee CHOI ; In-Cheol CHOI ; Sang-Bum HONG ; Tae Sun SHIM ; Hyeong Ryul KIM ; Dong Kwan KIM ; Seung-Il PARK
Infection and Chemotherapy 2020;52(4):600-610
Background:
The timeline of infections after lung transplantation has been changed with the introduction of new immunosuppressants and prophylaxis strategies. The study aimed to investigate the epidemiological characteristics of infectious diseases after lung transplantation in the current era.
Materials and Methods:
All patients who underwent lung or heart–lung transplantation at our institution between October 29, 2008 and April 3, 2019 were enrolled. We retrospectively reviewed the patients' medical records till April 2, 2020.
Results:
In total, 100 consecutive lung transplant recipients were enrolled. The median follow-up period was 28 months after lung transplantation. A total of 127 post–lung transplantation bacterial infections occurred. Catheter-related bloodstream infection (25/84, 29.8%) was the most common within 6 months and pneumonia (23/43, 53.5%) was the most common after 6 months. Most episodes (35/40, 87.5%) of respiratory viral infections occurred after 6 months, mainly as upper respiratory infections. The remaining episodes (5/40, 12.5%) mostly manifested as lower respiratory tract infections. Seventy cytomegalovirus infections observed in 43 patients were divided into 23 episodes occurring before and 47 episodes occurring after discontinuing prophylaxis. Of 10 episodes of cytomegalovirus disease, four occurred during prophylaxis and six occurred after prophylaxis.Of 23 episodes of post–lung transplantation fungal infection, 7 were aspergillosis and all occurred after the discontinuation of prophylaxis.
Conclusion
Lung transplant recipients experienced a high burden of infection even after 6 months, especially after the end of the prophylaxis period. Therefore, these patients should be continued to be monitored long-term for infectious disease.

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