Purpose: The role of allogeneic stem cell transplantation (alloSCT) in multiple myeloma (MM) treatment remains controversial. We conducted a retrospective, multicenter, nationwide study in Korea to evaluate the outcomes of alloSCT in Asian patients with MM. Materials and Methods: Overall, 109 patients with MM who underwent alloSCT between 2003 and 2020 were included in this study. Data were collected from the Korean Multiple Myeloma Working Party Registry. Results: The overall response rate and stringent complete response plus complete response (CR) rates were 67.0 and 46.8%, respectively, after alloSCT. At a median follow-up of 32.5 months, the 3-year probability of progression-free survival (PFS) and overall survival (OS) rates were 69.3% and 71.8%, respectively. The 3-year probabilities of OS rates in the upfront alloSCT, tandem auto-alloSCT, and later alloSCT groups were 75.0%, 88.9%, and 61.1%, respectively. Patients who achieved CR before or after alloSCT had significantly longer OS (89.8 vs. 18 months and 89.8 vs. 15.2 months, respectively). Even though patients who did not achieve CR prior to alloSCT, those who achieve CR after alloSCT had improved PFS and OS compared to those who had no achievement of CR both prior and after alloSCT. Patients who underwent alloSCT with 1-2 prior treatment lines had improved PFS (22.4 vs. 4.5 months) and OS (45.6 vs. 15.3 months) compared to those with three or more prior treatment lines. Conclusion AlloSCT may be a promising therapeutic option especially for younger, chemosensitive patients with earlier implementation from relapse.

Purpose: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. Methods The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuumassisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years.Discussion: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients.

Background: The efficacy and safety of denosumab have been established in a phase 3, randomized, placebo-controlled trial in Korean postmenopausal women with osteoporosis. This postmarketing surveillance study was aimed to investigate the safety and effectiveness of denosumab in Korean real-world clinical practice. Methods: Patients with osteoporosis who had received denosumab per the Korean approved indications in the postmarketing setting between September 2014 and September 2019 were enrolled. The primary endpoint was the incidence of adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was the percent change from baseline in bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck. Results: Of the 3,221 patients enrolled, 3,185 were included in the safety analysis set; 2,973 (93.3%) were female, and the mean± standard deviation (SD) age was 68.9±9.9 years. The mean±SD study period was 350.0±71.4 days. AEs, fatal AEs, and ADRs occurred in 19.3%, 0.8%, and 1.6%, respectively. The most frequent AEs, occurring in >0.5% of patients, were dizziness (0.7%), arthralgia (0.7%), back pain (0.6%), and myalgia (0.6%). Hypocalcemia occurred in 0.3% of patients. There were no cases of osteonecrosis of the jaw and atypical femoral fracture. Mean±SD percent change from baseline in BMD of the lumbar spine, total hip, and femoral neck was 7.3%±23.6%, 3.6%±31.4%, and 3.2%±10.7%, respectively. Conclusion The safety and effectiveness of denosumab in Korean patients with osteoporosis in this study were comparable with those in the Korean randomized controlled trial, with no new safety findings.

Purpose: We aimed to investigate variations in the risk of low back pain (LBP), lower extremity muscle pain, and whole body fatigue according to differences in prolonged standing work hours in relation to risk factor exposure and rest frequency. Materials and Methods: From the fifth Korean Working Conditions Survey data collected in 2017, data for 32970 full-time workers who worked for more than 1 year at their present job were analyzed. We classified the workers according to exposure to fatigue or painful postures, carrying heavy objects, performance of repetitive movements that burden the musculoskeletal system, and how often they took a break. Relationships between time spent in a standing posture at work and risks of LBP, lower extremity muscle pain, and whole body fatigue were analyzed by multivariate logistic regression. Results: Of the full-time workers in the survey, 48.7% worked in a standing position for more than half of their total working hours. A higher odds ratio (OR) value for lower extremity muscle pain was observed in female not exposed to carrying heavy objects [OR: 3.551, 95% confidence interval (CI): 3.038–4.150] and not exposed to performing repetitive movements (OR: 3.555, 95% CI: 2.761–4.557). Conclusion Changes in work methodologies are needed to lower the number of hours spent in a prolonged standing posture at work, including being able to rest when workers want to do so, to reduce pain and fatigue.

Purpose: We aimed to investigate variations in the risk of low back pain (LBP), lower extremity muscle pain, and whole body fatigue according to differences in prolonged standing work hours in relation to risk factor exposure and rest frequency. Materials and Methods: From the fifth Korean Working Conditions Survey data collected in 2017, data for 32970 full-time workers who worked for more than 1 year at their present job were analyzed. We classified the workers according to exposure to fatigue or painful postures, carrying heavy objects, performance of repetitive movements that burden the musculoskeletal system, and how often they took a break. Relationships between time spent in a standing posture at work and risks of LBP, lower extremity muscle pain, and whole body fatigue were analyzed by multivariate logistic regression. Results: Of the full-time workers in the survey, 48.7% worked in a standing position for more than half of their total working hours. A higher odds ratio (OR) value for lower extremity muscle pain was observed in female not exposed to carrying heavy objects [OR: 3.551, 95% confidence interval (CI): 3.038–4.150] and not exposed to performing repetitive movements (OR: 3.555, 95% CI: 2.761–4.557). Conclusion Changes in work methodologies are needed to lower the number of hours spent in a prolonged standing posture at work, including being able to rest when workers want to do so, to reduce pain and fatigue.

PURPOSE: Metabolic syndrome (MetS) is a major public health problem related to increased risks of cardiovascular disease and type 2 diabetes. We investigated whether recommended levels of leisure time physical activity (LTPA) decrease the risk of MetS in a community-based prospective cohort study (Ansung and Ansan cohort).MATERIALS AND METHODS: A total of 3910 adults (1890 men, 2020 women) without MetS examined in 2001–2002 (baseline) were included in this study and followed up from 2013 to 2014. We measured LTPA energy expenditure using the standard metabolic equivalent value [metabolic equivalent of task (MET)-h/wk]. Individuals were categorized into five groups (physically inactive, 0.1 to <7.5, 7.5 to <15.0, 15.0 to <22.5, 22.5 to <40.0, and ≥40.0 MET-h/wk).RESULTS: The mean follow-up period was 11.8 years. Among the cohort, 482 men (25.5%) and 541 women (26.8%) were diagnosed with newly developed MetS. Multivariate logistic analysis revealed a 4.4% lower MetS risk among those performing two to three times the recommended minimum of 7.5 MET-h/wk [multivariate relative risk (RR), 0.956; 95% confidence interval (CI), 0.654–1.398] and a 21.9% lower risk among those performing three to four times the physical activity minimum (multivariate RR, 0.781; 95% CI, 0.574–1.063). This association was only significant in females performing three to four times the minimum (crude RR, 0.655; 95% CI, 0.432–0.994).CONCLUSION: We noted that physical activity at more than 2 times the recommended minimum prevents MetS. Healthcare professionals should encourage inactive adults to be physically active during their leisure time to take advantage of its health benefits.
Adult ; Cardiovascular Diseases ; Cohort Studies ; Delivery of Health Care ; Energy Metabolism ; Female ; Follow-Up Studies ; Gyeonggi-do ; Humans ; Insurance Benefits ; Korea ; Leisure Activities ; Male ; Metabolic Equivalent ; Motor Activity ; Prospective Studies ; Public Health

Background: The fatality rate of patients with coronavirus disease 2019 (COVID-19) varies among countries owing to demographics, patient comorbidities, surge capacity of healthcare systems, and the quality of medical care. We assessed the clinical outcomes of patients with COVID-19 during the first wave of the epidemic in Korea. Methods: Using a modified World Health Organization clinical record form, we obtained clinical data for 3,060 patients with COVID-19 treated at 55 hospitals in Korea. Disease severity scores were defined as: 1) no limitation of daily activities; 2) limitation of daily activities but no need for supplemental oxygen; 3) supplemental oxygen via nasal cannula; 4) supplemental oxygen via facial mask; 5) non-invasive mechanical ventilation; 6) invasive mechanical ventilation; 7) multi-organ failure or extracorporeal membrane oxygenation therapy; and 8) death. Recovery was defined as a severity score of 1 or 2, or discharge and release from isolation. Results: The median age of the patients was 43 years of age; 43.6% were male. The median time from illness onset to admission was 5 days. Of the patients with a disease severity score of 3–4 on admission, 65 (71.5%) of the 91 patients recovered, and 7 (7.7%) died due to illness by day 28. Of the patients with disease severity scores of 5–7, 7 (19.5%) of the 36 patients recovered, and 8 (22.2%) died due to illness by day 28. None of the 1,324 patients who were < 50 years of age died; in contrast, the fatality rate due to illness by day 28 was 0.5% (2/375), 0.9% (2/215), 5.8% (6/104), and 14.0% (7/50) for the patients aged 50–59, 60–69, 70–79, and ≥ 80 years of age, respectively. Conclusion In Korea, almost all patients of < 50 years of age with COVID-19 recovered without supplemental oxygen. In patients of ≥ 50 years of age, the fatality rate increased with age, reaching 14% in patients of ≥ 80 years of age.

BACKGROUND: Bendamustine may be a potential treatment option for patients with myeloma, but little is known about the utility of bendamustine as a salvage treatment, especially in Asian patients. METHODS: We performed a multicenter retrospective study of patients with relapsed or refractory myeloma who received bendamustine and prednisone. RESULTS: The records of 65 heavily pre-treated patients, who had undergone bortezomib and lenalidomide treatment (median number of previous treatments: 5), were analyzed. The median time from diagnosis to bendamustine treatment was 3.8 years, and the median patient age was 63 years (range, 38‒77 yr). The responses to the last treatment before bendamustine were refractory disease (N=52, 80%) or disease progression from partial response (N=13, 20%). Twenty-three patients responded to the treatment, with an overall response rate of 35% (23/65), and the median number of bendamustine treatment cycles was two (range, 1‒5 cycles). The median overall survival after bendamustine treatment was 5.5 months and the overall survival rate in responders to bendamustine was significantly better than that in non-responders (P=0.036). CONCLUSION: Bendamustine may be a potential salvage treatment to extend survival in a select group of heavily pre-treated patients with relapsed or refractory myeloma.
Asian Continental Ancestry Group ; Bendamustine Hydrochloride* ; Bortezomib ; Diagnosis ; Disease Progression ; Humans ; Multiple Myeloma* ; Prednisone ; Retrospective Studies* ; Salvage Therapy ; Survival Rate

CTHRC1 (collagen triple-helix repeat-containing 1), a protein secreted during the tissue-repair process, is highly expressed in several malignant tumors, including pancreatic cancer. We recently showed that CTHRC1 has an important role in the progression and metastasis of pancreatic cancer. Although CTHRC1 secretion affects tumor cells, how it promotes tumorigenesis in the context of the microenvironment is largely unknown. Here we identified a novel role of CTHRC1 as a potent endothelial activator that promotes angiogenesis by recruiting bone marrow-derived cells to the tumor microenvironment during tumorigenesis. Recombinant CTHRC1 (rCTHRC1) enhanced endothelial cell (EC) proliferation, migration and capillary-like tube formation, which was consistent with the observed increases in neovascularization in vivo. Moreover, rCTHRC1 upregulated angiopoietin-2 (Ang-2), a Tie2 receptor ligand, through ERK-dependent activation of AP-1 in ECs, resulting in recruitment of Tie2-expressing monocytes (TEMs) to CTHRC1-overexpressing tumor tissues. Treatment with a CTHRC1-neutralizing antibody-abrogated Ang-2 expression in the ECs in vitro. Moreover, administration of a CTHRC1-neutralizing antibody to a xenograft mouse model reduced the tumor burden and infiltration of TEMs in the tumor tissues, indicating that blocking the CTHRC1/Ang-2/TEM axis during angiogenesis inhibits tumorigenesis. Collectively, our findings support the hypothesis that CTHRC1 induction of the Ang-2/Tie2 axis mediates the recruitment of TEMs, which are important for tumorigenesis and can be targeted to achieve effective antitumor responses in pancreatic cancers.
Angiopoietin-2 ; Animals ; Carcinogenesis ; Endothelial Cells ; Heterografts ; In Vitro Techniques ; Mice ; Monocytes* ; Neoplasm Metastasis ; Pancreatic Neoplasms ; Receptor, TIE-2 ; Transcription Factor AP-1 ; Tumor Burden ; Tumor Microenvironment

OBJECTIVE: This study was conducted to assess the efficacy and safety of endovascular mechanical thrombectomy (EMT) for patients diagnosed with basilar artery (BA) occlusion. MATERIALS AND METHODS: We retrospectively analyzed clinical and imaging data of 16 patients diagnosed with BA occlusion who were treated with endovascular intervention from July 2012 to February 2013. Direct suction using the Penumbra system and thrombus retrieval by the Solitaire stent were the main endovascular techniques used to restore BA flow. The outcomes were evaluated based on rate of angiographic recanalization, rate of improvement of National Institutes of Health Stroke Scale (NIHSS) score, rate of modified Rankin Scale (mRS) at discharge and after 3 months, and rate of cerebral hemorrhagic complications. Successful recanalization was defined as achieving Thrombolysis In Cerebral Infarction (TICI) of II or III. RESULTS: Sixteen patients received thrombectomy. The mean age was 67.8 +/- 11 years and the mean NIHSS score was 12.3 +/- 8.2. Eight patients treated within 6 hours of symptom onset were grouped as A and the other 8 patients treated beyond 6 hours (range, 6-120) were grouped as B. Successful recanalization was met in six patients (75%) for group A and 7 (87.5%) for group B. Favorable outcome occurred in 4 patients (50%) for group A and 5 (62.5%) for group B. CONCLUSION: Our study supports the effectiveness and safety of endovascular mechanical thrombectomy in treating BA occlusion even 6 hours after symptom onset.
Basilar Artery ; Cerebral Infarction ; Endovascular Procedures ; Humans ; National Institutes of Health (U.S.) ; Retrospective Studies ; Stents ; Stroke ; Suction ; Thrombectomy ; Thrombosis