1.Clinical Characteristics, Diagnosis, and Treatment of Thyroid Stimulating Hormone-Secreting Pituitary Neuroendocrine Tumor (TSH PitNET): A Single-Center Experience
Jung HEO ; Yeon-Lim SUH ; Se Hoon KIM ; Doo-Sik KONG ; Do-Hyun NAM ; Won-Jae LEE ; Sung Tae KIM ; Sang Duk HONG ; Sujin RYU ; You-Bin LEE ; Gyuri KIM ; Sang-Man JIN ; Jae Hyeon KIM ; Kyu Yeon HUR
Endocrinology and Metabolism 2024;39(2):387-396
Background:
Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity.
Methods:
A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared.
Results:
Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered.
Conclusion
The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.
2.The Modified S-GRAS Scoring System for Prognosis in Korean with Adrenocortical Carcinoma
Sun Kyung BAEK ; Seung Hun LEE ; Seung Shin PARK ; Chang Ho AHN ; Sung Hye KONG ; Won Woong KIM ; Yu-Mi LEE ; Su Jin KIM ; Dong Eun SONG ; Tae-Yon SUNG ; Kyu Eun LEE ; Jung Hee KIM ; Kyeong Cheon JUNG ; Jung-Min KOH
Endocrinology and Metabolism 2024;39(5):803-812
Background:
Adrenocortical carcinomas (ACCs) are rare tumors with aggressive but varied prognosis. Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score, based on clinical and pathological factors, was found to best stratify the prognosis of European ACC patients. This study assessed the prognostic performance of modified S-GRAS (mS-GRAS) scores including modified grade (mG) by integrating mitotic counts into the Ki67 index (original grade), in Korean ACC patients.
Methods:
Patients who underwent surgery for ACC between January 1996 and December 2022 at three medical centers in Korea were retrospectively analyzed. mS-GRAS scores were calculated based on tumor stage, mG (Ki67 index or mitotic counts), resection status, age, and symptoms. Patients were divided into four groups (0–1, 2–3, 4–5, and 6–9 points) based on total mS-GRAS score. The associations of each variable and mS-GRAS score with recurrence and survival were evaluated using Cox regression analysis, Harrell’s concordance index (C-index), and the Kaplan–Meier method.
Results:
Data on mS-GRAS components were available for 114 of the 153 patients who underwent surgery for ACC. These 114 patients had recurrence and death rates of 61.4% and 48.2%, respectively. mS-GRAS score was a significantly better predictor of recurrence (C-index=0.829) and death (C-index=0.747) than each component (P<0.05), except for resection status. mS-GRAS scores correlated with shorter progression-free survival (P=8.34E-24) and overall survival (P=2.72E-13).
Conclusion
mS-GRAS scores showed better prognostic performance than tumor stage and grade in Asian patients who underwent surgery for ACC.
3.Rehabilitation after Repair of Medial Meniscus Posterior Root Tears: A Systematic Review of the Literature
Jin Seong KIM ; Min Ki LEE ; Moon Young CHOI ; Doo Hwan KONG ; Jeong Ku HA ; Jin Goo KIM ; Kyu Sung CHUNG
Clinics in Orthopedic Surgery 2023;15(5):740-751
Background:
There is no consensus established on postoperative rehabilitation after medial meniscus posterior root tear (MMPRT) repair, including when and how physicians can apply range of motion (ROM) exercise, weight-bearing (WB), brace use, and return to sports (RTS). The purpose of this study was to systematically review the literature on postoperative rehabilitation characteristics of MMPRT repair regarding ROM, WB, brace use, and RTS.
Methods:
A literature search was performed using the Medline/PubMed, Cochrane Central Register of Controlled Trials, and Embase databases. The inclusion criteria were English language, human clinical studies, and studies describing rehabilitation protocols after MMPRT repair such as ROM, WB, brace use, and RTS. Abstracts, case reports, cohort studies, controlled laboratory studies, human cadaveric or animal studies, systematic reviews, and meta-analyses were excluded.
Results:
Thirteen studies were included. Of the 12 ROM studies, ROM was started immediately within 1 or 2 days after operation in 6 studies and after 2 to 3 weeks of knee immobilization in the rest. Of the 13 WB studies, partial weight-bearing was initiated 1 to 4 weeks after operation in 8 studies and 6 weeks in the rest. Of the 9 brace studies, patients were immobilized by a splint for 2 weeks in 3 studies, and in the rest, a brace with full extension was applied for 3 to 6 weeks after several days of splint application.Of the 7 RTS studies, RTS was allowed at 6 months in 6 studies and 5 to 7 months in 1 study.
Conclusions
This systematic review revealed conservative rehabilitation protocols were more widely adapted as ROM and WB were restricted at certain degrees during postoperative periods in most protocols analyzed. However, it is impossible to identify a consensus on rehabilitation protocols as the protocols analyzed in this review were distinct each other and heterogeneous. In the future, a well-designed comparative study among different rehabilitation protocols is essential to establish a consensus.
4.Does a Lower Limb Balance Test after Anterior Cruciate Ligament Reconstruction Have a Significant Correlation with Postoperative Clinical Score, Stability, and Functional Performance Test?
Jin Seong KIM ; Moon Young CHOI ; Doo Hwan KONG ; Jeong Ku HA ; Kyu Sung CHUNG
Clinics in Orthopedic Surgery 2023;15(3):402-409
Background:
Lower limb balance ability is reduced after anterior cruciate ligament reconstruction (ACLR). However, the recovery of balance based on functional test scores after ACLR is not known because the correlation between balance and clinical scores remains unclear. We aimed to analyze the correlation between lower limb balance assessed by functional test and clinical knee test scores after ACLR.
Methods:
We evaluated lower limb balance using the anterior-posterior stability index (APSI) of the Biodex Balance System (BBS).Patients underwent clinical tests to evaluate the knee, including the Tegner activity score, International Knee Documentation Committee (IKDC) subjective score, Lysholm score, and KT-2000 arthrometer measurement, hamstring per quadriceps muscle strength ratio at 60°/sec (HQ ratio), and functional performance tests (single-leg hop and single-leg vertical jump tests) 1 year after ACLR.We used a paired t-test to compare continuous preoperative and postoperative variables and Pearson’s correlation coefficient to determine the relationship between BBS-APSI and clinical scores.
Results:
Forty-eight patients (35 men and 13 women; mean age, 28.9 ± 8.3 years) were included. The follow-up period and BBSAPSI were 12.4 ± 2.0 months and 0.9 ± 0.4, respectively. Tegner activity score, IKDC subjective score, Lysholm score, and KT-2000 arthrometer measurement improved significantly postoperatively (p < 0.001). BBS-APSI was correlated with the Tegner activity score (r = –0.335, p = 0.020), IKDC subjective score (r = –0.301, p = 0.037), Lysholm score (r = –0.323, p = 0.025), single-leg hop test results (r = –0.300, p = 0.038), and single-leg vertical jump test results (r = –0.336, p = 0.019). There was no correlation between KT-2000 arthrometer measurement and HQ ratio.
Conclusions
BBS-APSI was correlated with functional performance test scores after ACLR, rendering the BBS-APSI as a useful assessment tool to evaluate postoperative functional recovery. Continuously improving balance after ACLR could be useful for functional recovery after surgery.
5.Busulfan, Melphalan, and Etoposide (BuME) Showed an Equivalent Effect to Busulfan, Cyclophosphamide, and Etoposide (BuCE) as Conditioning Therapy for Autologous Stem Cell Transplantation in Patients with Relapsed or High-Risk Non-Hodgkin’s Lymphoma: A Multicenter Randomized Phase II Study bythe Consortium for Improving Survival of Lymphoma (CISL)
Kyoung Ha KIM ; Jae Hoon LEE ; Mark LEE ; Hoon-Gu KIM ; Young Rok DO ; Yong PARK ; Sung Yong OH ; Ho-Jin SHIN ; Won Seog KIM ; Seong Kyu PARK ; Jee Hyun KONG ; Moo-Rim PARK ; Deok-Hwan YANG ; Jae-Yong KWAK ; Hye Jin KANG ; Yeung-Chul MUN ; Jong-Ho WON
Cancer Research and Treatment 2023;55(1):304-313
Purpose:
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin’s lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL.
Materials and Methods:
Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days –7, –6, and –5, etoposide (400 mg/m2 intravenously) on days –5 and –4, and melphalan (50 mg/m2/day intravenously) on days –3 and –2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days –7, –6, and –5, etoposide (400 mg/m2/day intravenously) on days –5 and –4, and cyclophosphamide (50 mg/kg/day intravenously) on days –3 and –2. The primary endpoint was 2-year progression-free survival (PFS).
Results:
Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation.
Conclusion
There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.
6.Development of a Spine X-Ray-Based Fracture Prediction Model Using a Deep Learning Algorithm
Sung Hye KONG ; Jae-Won LEE ; Byeong Uk BAE ; Jin Kyeong SUNG ; Kyu Hwan JUNG ; Jung Hee KIM ; Chan Soo SHIN
Endocrinology and Metabolism 2022;37(4):674-683
Background:
Since image-based fracture prediction models using deep learning are lacking, we aimed to develop an X-ray-based fracture prediction model using deep learning with longitudinal data.
Methods:
This study included 1,595 participants aged 50 to 75 years with at least two lumbosacral radiographs without baseline fractures from 2010 to 2015 at Seoul National University Hospital. Positive and negative cases were defined according to whether vertebral fractures developed during follow-up. The cases were divided into training (n=1,416) and test (n=179) sets. A convolutional neural network (CNN)-based prediction algorithm, DeepSurv, was trained with images and baseline clinical information (age, sex, body mass index, glucocorticoid use, and secondary osteoporosis). The concordance index (C-index) was used to compare performance between DeepSurv and the Fracture Risk Assessment Tool (FRAX) and Cox proportional hazard (CoxPH) models.
Results:
Of the total participants, 1,188 (74.4%) were women, and the mean age was 60.5 years. During a mean follow-up period of 40.7 months, vertebral fractures occurred in 7.5% (120/1,595) of participants. In the test set, when DeepSurv learned with images and clinical features, it showed higher performance than FRAX and CoxPH in terms of C-index values (DeepSurv, 0.612; 95% confidence interval [CI], 0.571 to 0.653; FRAX, 0.547; CoxPH, 0.594; 95% CI, 0.552 to 0.555). Notably, the DeepSurv method without clinical features had a higher C-index (0.614; 95% CI, 0.572 to 0.656) than that of FRAX in women.
Conclusion
DeepSurv, a CNN-based prediction algorithm using baseline image and clinical information, outperformed the FRAX and CoxPH models in predicting osteoporotic fracture from spine radiographs in a longitudinal cohort.
7.Aqueous Humor Cytokine Levels and Choroidal Thicknesses of Patients with Age‐related Macular Degeneration and Pachychoroid Neovasculopathy
Jeong Han KONG ; Yong Dae KIM ; Sung Pyo PARK ; Yong‐Kyu KIM
Journal of the Korean Ophthalmological Society 2022;63(4):361-369
Purpose:
We sought correlations between the subfoveal choroidal thickness (SCT) and changes in the levels of aqueous humor cytokines before and after anti‐vascular endothelial growth factor (anti‐VEGF) treatment of patients with neovascular age‐related macular degeneration (nAMD) and pachychoroid neovasculopathy.
Methods:
We measured changes in the SCT and levels of aqueous humor cytokines (VEGF, soluble VEGF receptor‐2 [sVEGFR‐ 2], platelet‐derived growth factor [PDGF]‐AA, monocyte chemoattractant protein 1 [MCP‐1], interleukin [IL]‐6, and IL‐8) after anti‐ VEGF treatment of 11 eyes of 11 nAMD patients and nine eyes of nine pachychoroid neovasculopathy patients. The aqueous humor cytokine levels were compared between the two groups.
Results:
After anti‐VEGF treatment, the aqueous levels of VEGF and PDGF‐AA decreased significantly, whereas that of sVEGFR‐2 increased. The amount of change in sVEGFR‐2 concentration before and after anti‐VEGF treatment correlated with the SCT and its change after treatment. nAMD patients with relatively thin SCTs and smaller SCT changes after anti‐VEGF treatment showed greater increases in sVEGFR‐2 levels following treatment. We found significant correlations among the MCP‐1, IL‐6, and IL‐8 levels in the nAMD group, and between the sVEGFR‐2 and MCP‐1, and MCP‐1 and PDGF‐AA, levels in the pachychoroid neovasculopathy group.
Conclusions
Patients with nAMD exhibited significant increases in aqueous sVEGFR‐2 levels following anti‐VEGF treatment and significant correlations among the levels of the inflammatory cytokines MCP‐1, IL‐6, and IL‐8, suggesting that angiogenic factors and inflammatory cytokines may affect the pathophysiologies of the two diseases differently.
8.Effect of Denosumab on the Change of Osteoclast Precursors Compared to Zoledronate Treatment in Postmenopausal Women with Osteoporosis
Sung Hye KONG ; Jung Hee KIM ; Sang Wan KIM ; Ae Jin JEONG ; Song-Hee LEE ; Sang-Kyu YE ; Chan Soo SHIN
Journal of Bone Metabolism 2022;29(2):93-101
Background:
A rapid increase in bone turnover and bone loss has been observed in response to the discontinuation of denosumab. It led to an acute increase in the fracture risk, similar to that observed in the untreated patients. We aimed to investigate the effect of denosumab on osteoclast (OC) precursor cells compared to that of zoledronate.
Methods:
The study compared the effects of denosumab (60 mg/24-week) and zoledronate (5 mg/48-week) over 48 weeks in postmenopausal women with osteoporosis. From patients’ peripheral mononuclear cells, CD14+/CD11b+/vitronectin receptor (VNR)- and CD14+/CD11b+/VNR+ cells were isolated using fluorescent-activated cell sorting, representing early and late OC precursors, respectively. The primary endpoint was the changes in OC precursors after 48 weeks of treatment.
Results:
Among the 23 patients, 11 were assigned to the denosumab group and 12 to the zoledronate group (mean age, 69 years). After 48 weeks, the changes in OC precursors were similar between and within the groups. Serum C-terminal telopeptide of type I collagen levels were inversely correlated with OC precursor levels after denosumab treatment (r=-0.72, P<0.001). Lumbar spine, femur neck, and total hip bone mineral density (BMD) increased in both groups. Lumbar spine BMD increased more significantly in the denosumab group than in the zoledronate group.
Conclusions
Denosumab and zoledronate treatments induced similar changes in OC precursors. During denosumab treatment, old age and suppressed bone turnover were associated with increased OC precursor cell populations. Further validation studies with prospective designs are required.
9.An Increasing Trend in the Number of Anterior Cruciate Ligament Reconstruction in Korea: A Nationwide Epidemiologic Study
Kyu Sung CHUNG ; Jung Hoon KIM ; Doo Hwan KONG ; InKeun PARK ; Jin Goo KIM ; Jeong Ku HA
Clinics in Orthopedic Surgery 2022;14(2):220-226
Background:
Most epidemiologic studies of anterior cruciate ligament reconstruction (ACLR) to date have been conducted in Western populations, whereas no studies have been conducted in Asian populations. In this study, the incidence and trend of ACLR in Korea were investigated through an epidemiological big data analysis.
Methods:
The data were collected by the Health Insurance Review and Assessment Service from 2008 to 2016 in Korea. Patient records with the coding of cruciate ligament reconstruction were allocated, and ACLR patients were further refined by medical diagnosis coding. The total number and incidence of ACLR procedures per 100,000 person-years were investigated and more detailed analysis was conducted according to sex and age. Furthermore, concomitant surgical procedures performed during ACLR were investigated.
Results:
The total number and incidence of ACLR procedures rose from 10,248 and 21.8 to 14,500 and 29.1 between 2008 and 2016, respectively. The incidence of ACLR procedures increased by 33.5% over this 9-year period. Over this period, the total number and incidence increased from 8,543 and 36.4 to 11,534 and 46.4, respectively, in males and from 1,705 and 7.2 to 2,966 and 11.9, respectively, in females. ACLR was performed more frequently in males than in females; however, the increase rate was higher in females than males. ACLR was performed most frequently in patients in their 20s, followed by patients in their 30s, 40s, and 10s. The most frequent concomitant procedures performed during ACLR were meniscectomy (13.6% in 2008 and 9.8% in 2016) and meniscal repair (5.8% in 2008 and 8.8% in 2016).
Conclusions
The incidence of ACLR consistently rose between 2008 and 2016 in Korea. The current study will enhance our understanding of the epidemiology of ACLR, which is needed to devise cost-effective preventive measures.
10.National Trends of Meniscectomy and Meniscus Repair in Korea
Kyu Sung CHUNG ; Jeong Ku HA ; Yoon Seok KIM ; Jung Hoon KIM ; Ho Jong RA ; Doo Hwan KONG ; Pei Wei WANG ; Choong Hyeok CHOI ; Jin Goo KIM
Journal of Korean Medical Science 2019;34(32):e206-
BACKGROUND: Meniscus surgeries are frequently performed in orthopaedics. However, their current status is not well known in many countries, including Korea. This study aimed to investigate the national trends of meniscus surgery in Korea. METHODS: Information from the national database was acquired through the Korean Health Insurance Review and Assessment Service from 2010 to 2017. All cases coded as meniscectomy or meniscus repair were included. The total number and incidence of cases of meniscus surgery per 100,000 persons were determined, and the results were stratified by age and gender. The meniscus repair ratio for the total number of meniscus surgeries was evaluated. RESULTS: The total number and incidence of meniscectomy cases were 65,752 and 137, respectively, in 2010, which increased to 74,088 and 154, respectively, in 2017. The number of meniscectomies increased by 12.67% in 8 years. The total number and incidence of meniscus repair cases were 9,055 and 18, respectively, in 2010, which increased to 14,947 and 31 in 2017. The number of meniscus repairs increased by 65.04%. The meniscus repair ratio was 12.1% in 2010, which increased to 16.8% in 2017. The highest peak was noted for patients who underwent meniscus surgeries in their 50s and 60s. Meniscectomy was performed more frequently in women (57%) than in men (43%), whereas repair was performed more frequently in men (54%) than in women (46%) over the study period. CONCLUSION: The total number and incidence of meniscus surgeries increased from 2010 to 2017; the number and incidence of meniscus repair procedures increased more rapidly than those of meniscectomy, with the peak treatment age for both surgeries being in the 50s and 60s. The current study will contribute to understanding the epidemiology of meniscus surgery, its prevention, and cost-saving measures in Korea.
Epidemiology
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Female
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Humans
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Incidence
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Insurance, Health
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Korea
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Male

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