Previous studies have reported the survival benefit after ruxolitinib treatment in patients with myelofibrosis (MF). However, population-based data of its efficacy are limited. We analyzed the effects of ruxolitinib in MF patients with data from the Korean National Health Insurance Database. In total, 1199 patients diagnosed with MF from January 2011 to December 2017 were identified, of which 731 were included in this study. Patients who received ruxolitinib (n = 224) were matched with those who did not receive the drug (n = 507) using the 1:1 greedy algorithm. Propensity scores were formulated using five variables: age, sex, previous history of arterial/venous thrombosis, and red blood cell (RBC) or platelet (PLT) transfusion dependence at the time of diagnosis. Cox regression analysis for overall survival (OS) revealed that ruxolitinib treatment (hazard ratio (HR), 0.67; p = 0.017) was significantly related to superior survival. In the multivariable analysis for OS, older age (HR, 1.07; p < 0.001), male sex (HR, 1.94; p = 0.021), and RBC (HR, 3.72; p < 0.001) or PLT (HR, 9.58; p = 0.001) transfusion dependence were significantly associated with poor survival, although type of MF did not significantly affect survival. Considering evidence supporting these results remains weak, further studies on the efficacy of ruxolitinib in other populations are needed.
Abstract Background This study assessed the mechanism of hematopoietic stem cell (HSC) mobilization using etoposide with granulocyte-colony stimulating factor (G-CSF) and determined how it differed from that using cyclophosphamide with G-CSF or G-CSF alone.Methods The study analyzed data from 173 non-Hodgkin’s lymphoma patients who underwent autologous peripheral blood stem cell transplantation (auto-PBSCT), in vitro experiments using HSCs and bone marrow stromal cells (BMSCs), and in vivo mouse model studies.Results The etoposide with G-CSF mobilization group showed the highest yield of CD34+ cells and the lowest change in white blood cell counts during mobilization. Etoposide triggered interleukin (IL)-8 secretion from BMSCs and caused long-term BMSC toxicity, which were not observed with cyclophosphamide treatment. The expansion of CD34+ cells cultured in BMSC-conditioned medium containing IL-8 was more remarkable than that without IL-8. The expression of CXCR2, mTOR, and cMYC in HSCs was gradually enhanced at 1, 6, and 24 h after IL-8 stimulation. In animal studies, the etoposide with G-CSF mobilization group presented stronger expression of IL-8-related cytokines and MMP9 and scantier expression of SDF-1 in the bone marrow, compared to the other groups not treated with etoposide.Conclusion Collectively, the unique mechanism of etoposide with G-CSF-mediated mobilization is associated with the secretion of IL-8 from BMSCs, causing the enhanced proliferation and mobilization of HSCs in the bone marrow, which was not observed in the mobilization using cyclophosphamide with G-CSF or G-CSF alone. Moreover, the long-term toxicity of etoposide to BMSC emphasizes the need for further studies to develop more efficient and safe chemo-mobilization strategies.
This study presents the most comprehensive machine-learning analysis for the predictors of blood transfusion, all-cause mortality, and hospitalization period in COVID-19 patients. Data came from Korea National Health Insurance claims data with 7943 COVID-19 patients diagnosed during November 2019−May 2020. The dependent variables were all-cause mortality and the hospitalization period, and their 28 independent variables were considered. Random forest variable importance (GINI) was introduced for identifying the main factors of the dependent variables and evaluating their associations with these predictors, including blood transfusion. Based on the results of this study, blood transfusion had a positive association with all-cause mortality. The proportions of red blood cell, platelet, fresh frozen plasma, and cryoprecipitate transfusions were significantly higher in those with death than in those without death (p-values < 0.01). Likewise, the top ten factors of all-cause mortality based on random forest variable importance were the Charlson Comorbidity Index (53.54), age (45.68), socioeconomic status (45.65), red blood cell transfusion (27.08), dementia (19.27), antiplatelet (16.81), gender (14.60), diabetes mellitus (13.00), liver disease (11.19) and platelet transfusion (10.11). The top ten predictors of the hospitalization period were the Charlson Comorbidity Index, socioeconomic status, dementia, age, gender, hemiplegia, antiplatelet, diabetes mellitus, liver disease, and cardiovascular disease. In conclusion, comorbidity, red blood cell transfusion, and platelet transfusion were the major factors of all-cause mortality based on machine learning analysis. The effective management of these predictors is needed in COVID-19 patients.
목적: 초음파 검사 후 갑상선 결절 및 림프절 전이 유무 확인을 위해 시행하는 경부 CT(Thyroid with Neck) 검사에서 임상에서 사용하고 있는 고관전압 120 kVp 프로토콜과 CARE kV를 사용한 저관전압 70 kVp 프로토콜 간의 선량과 화질을 비교분석 하여 70 kVp 프로토콜의 선량감소 효과와 유용성에 관하여 알아보고자 한다. 대상 및 방법: 초음파 검사 후 갑상선 결절이 발견된 후 경부 CT 검사를 시행한 환자 64명을 대상으로 대조군(32명)은 관전압 120 kVp 프로토콜을 적용하였고, 실험군(32명)은 관전압 70kVp 프로토콜을 적용하였다. 영상의 정량적 평가는 총경동맥 (Common carotid artery: CCA), 속목정맥(internal jugular vein: I.J vein), 목빗근(Sternocleidomastoid muscle: S.C muscle) 그리고 백그라운드에 관심영역(region of interest; ROI)을 설정해 noise, 신호대 잡음비(signal to noise ratio; SNR), 대조도 대 잡음비 (contrast to noise ratio; CNR), CT HU(hounsfield unit)를 측정 비교하였다. 통계 분석은 PASW(PASW statistics, ver. 18.0, SPSS, Chicago, USA)을 이용하여 독립 표본 t-검정을 실시하였다. 정성적 평가는 경부 CT 판독 전문의 1명과 전공의 8명을 대상으로 Blind test 후 설문을 통하여 매우 그렇다(5점), 그렇다(4점), 보통이다(3점), 그렇지 않다(2점), 매우 그렇지 않다(1점) 로 평가 하였다. 선량 평가는 검사 후 Dose Report에 표시되는 DLP값을 이용하여 비교 분석 하였다. 결과: 정량적 평가 결과 HU 값은 대조군(A)과 실험군(B)의 총경동맥, 속목정맥, 목빗근이 유의한 차이가 있었다(CCA: (A) 188.22± 22.33 vs (B) 248.57±33.99, I.J vein: (A) 186.51±22.98 vs (B) 244.55±33.89, S.C muscle: (A) 73.52±6.78 vs (B) 69.39±5.89 p<0.05). 영상 noise는 실험군(B)에서 대조군(A)에 비해 유의하게 높았다(CCA: (A) 4.41±1.09 vs (B) 5.75±0.97, I.J vein: (A) 4.23±1.25 vs (B) 5.97±0.99, S.C muscle (A) 3.42±0.97 vs (B) 5.53±1.34 백그라운드: (A) 1.64±0.48 vs (B) 2.54±0.46 p<0.05). SNR은 대조군(A) 실험군(B)에서 총경동맥, 속목정맥은 유의한 차이가 없었으며, 목빗근은 유의한 차이가 있었다(CCA: (A) 45.02±11.73 vs (B) 44.41±9.66, p=0.821, I.J vein: (A) 47.61±14.251 vs (B) 44.03±47.61, p=0.233, S.C muscle (A) 21.95±5.79 vs (B) 16.84±2.59 p<0.05). CNR은 대조군(A)과 실험군(B)에서 유의한 차이가 없었다(CCA: (A) 75.65±25.87 vs (B) 72.86±19.74, p=0.629, I.J vein: (A) 74.46±25.78 vs (B) 71.14±18.80, p=0.558). 정성적 평가 결과 실험군 대조군 화질차이 인식(2.452±4.31)으로 매우 낮은 것으로 나타났고, 실험군 화질의 부족한 정도 인식(1.915±2.691), 실험군 판독 적합성 인식 (1.212 ±1.178)도 매우 낮은 것으로 나타났다. 선량 평가는 대조군(A)과 실험군(B)의 DLP 값이 유의한 차이가 있었다(DLP(A) 393.50±51.96 vs DLP(B) 98.69±30.58 p<0.05). 결론: 경부 CT(Thyroid with Neck) 검사시 기존에 사용하던 120 kVp 프로토콜과 CARE kV를 사용하여 관전압을 70 kVp 로설정한 프로토콜을 비교 분석하여 영상의 화질과 환자 선량 감소 효과에 대해 평가 하였다. 기존 고관전압 120kVp 프로토콜과 비교하여 저관전압 70 kVp 프로토콜은 적은 조영제의 사용량으로 갑상선 결절 및 림프절 전이 유무를 진단하는데 적합한 영상을 얻을 수 있으며, 환자 선량을 효과적으로 감소시킬 수 있어 갑상선 질환 환자들을 대상으로 매우 유용하리라 사료된다.Purpose: In order to investigate the dose reduction effect and the usefulness of the 70 kVp protocol by comparing the image quality between the high-voltage 120 kVp protocol, currently used in the clinical CT test of Cervical(Thyroid with Neck) which is implemented to confirm thyroid nodule and lymph node metastasis After ultrasound examination and the low-voltage 70 kVp using CARE kV. Material and methods: In 64 patients who underwent cervical(neck) CT after thyroid nodule was found by ultrasound examination, the control group (32 patients) applied the tube voltage 120 kVp protocol, whereas the experimental group(32 patients) applied the tube voltage 70 kVp protocol. Regarding the quantitative evaluation of the images, signal to noise ratio (SNR), contrast to noise ratio (CNR) and CT HU (Hounsfield Unit) were measured and compared by setting the common carotid artery (CCA), the internal jugular vein (IJ vein), the Sternocleidomastoid muscle (SC muscle), and the region of interest (ROI) and noise. Statistical analysis was implemented by independent sample t-test using PASW (PASW statistics, ver. 18.0, SPSS, Chicago, USA). Regarding the qualitative evaluation, the survey was conducted with criteria of highly agree (5point), agree (4points), average (3point), disagree(2points), strongly disagree(1point) after the blind test for one cervical(neck) CT reading specialist and eight residents. The dose assessment was implemented by comparing and analyzing DLP values shown in the Dose report after the test. Result: As a result of quantitative evaluation, HU value has significant difference between control group (A) and experimental group (B) in Common carotid artery, internal jugular vein and Sternocleidomastoid muscle (CCA: (A) 188.22±22.33 vs (B) 248.57±33.99, I.J vein: (A) 186.51±22.98 vs (B) 244.55±33.89, S.C muscle: (A) 73.52±6.78 vs (B) 69.39±5.89 p<0.05). Image noise was significantly higher in the experimental group (B) than in the control group (CCA: (A) 4.41±1.09 vs (B) 5.75±0.97, I.J vein: (A) 4.23±1.25 vs (B) 5.97±0.99, S.C muscle (A) 3.42±0.97 vs (B) 5.53±1.34 Background: (A) 1.64±0.48 vs (B) 2.54±0.46 p<0.05). SNR was not significantly different between the control group (A) and the experimental group (B)in common carotid artery and internal jugular vein, but had a significant difference in the sternocleidomastoid muscle. (CCA: (A) 45.02±11.73 vs (B) 44.41±9.66, p=0.821, I.J vein: (A) 47.61±14.251 vs (B) 44.03±47.61, p=0.233, S.C muscle (A) 21.95±5.79 vs (B) 16.84±2.59 p<0.05). CNR has no significant between control (A) and experimental group (B) (CCA: (A) 75.65±25.87 vs (B) 72.86±19.74, p=0.629, I.J vein: (A) 74.46±25.78 vs (B) 71.14±18.80, p=0.558). As a result of the qualitative evaluation, recognition of the image quality of the experimental group and the control group was very low (2.45±4.31). In the experimental group, the recognition of insufficiency about the image quality (1.915±2.691) and the recognition of the readability (1.212±1.178) were also very low. The dose assessment showed a significant difference in the DLP values between the control group (A) and the experimental group.(DLP(A) 393.50±51.96 vs DLP(B) 98.69±30.58 p<0.05). Conclusion: The image quality and the patient dose reduction effect were evaluated by comparing and analyzing the 120kVp protocol which was previously used upon CT test of Cervical(Thyroid with Neck) and the protocol which sets its tube voltage to 70kVp by using CARE kV. Compared to the conventional the high tube voltage protocol of 120kVp, the low tube voltage protocol of 70 kVp was able to obtain a suitable image for diagnosis of a thyroid nodule and lymph node metastasis with using a small amount of contrast medium and was able to reduce patient dose effectively. Therefore, the low tube voltage protocol is expected to be very useful for the patient with thyroid disease.
Interleukin-2 (IL-2) and its α receptor in soluble form (sIL-2Rα) are considered biomarkers for cancers and immune-related diseases. Enzyme-linked immunosorbent assay is the most common method used to evaluate biomarkers in clinical practice; it is precise but time-consuming and involves complicated procedures. Here, we have developed a rapid yet accurate modality for cancer diagnosis that enables on-site evaluation of cancer markers, that is, IL-2 and sIL-2Rα, without complicated pretreatment of cancer patient-derived blood samples. Surface plasmon resonance and bioresponsive microgels conjugated with IL-2 receptors, that is, IL-2Rβ and IL-2Rγ, were utilized to measure IL-2 and sIL-2Rα levels via multivalent protein binding (MPB) between the ligands and their receptors. Our results showed that this novel method enables us to perform cancer diagnosis with a 1000-fold dilution of serum in 10 min. The advantage of MPB-based cancer diagnosis originates from its great selectivity for a target molecule and tolerance to a myriad of nonspecific substances in serum, which allows on-site clinical evaluation. Importantly, our finding implies that MPB-based cancer diagnosis provides a new paradigm not only for improving cancer treatment but also for evaluating a target molecule in unpurified and complex solutions such as blood.
Induced pluripotent stem cell (iPSC) technology has great promise in regenerative medicine and disease modeling. In this study, we show that human placenta-derived cell conditioned medium stimulates chemokine (C-X-C motif) receptor 2 (CXCR2) in human somatic cells ectopically expressing the pluripotency-associated transcription factors Oct4, Sox2, Klf4, and cMyc (OSKM), leading to mechanistic target of rapamycin (mTOR) activation. This causes an increase in endogenous cMYC levels and a decrease in autophagy, thereby enhancing the reprogramming efficiency of human somatic cells into iPSCs. These findings were reproduced when human somatic cells after OSKM transduction were cultured in a widely used reprogramming medium (mTeSR) supplemented with CXCR2 ligands interleukin-8 and growth-related oncogene α or an mTOR activator (MHY1485). To our knowledge, this is the first report demonstrating that mTOR activation in human somatic cells with ectopic OSKM expression significantly enhances the production of iPSCs. Our results support the development of convenient protocols for iPSC generation and further our understanding of somatic cell reprogramming.
Multiple myeloma (MM) progresses with abnormal monoclonal proliferation and accumulation of malignant plasma cells in the bone marrow. We established human induced pluripotent stem cells (iPSCs), KUMi005-A, from bone marrow samples of a patient with MM. This reprogrammed cell line has similar characteristics to human embryonic stem cells, such as proliferation properties and pluripotency. KUMi005-A iPSCs may be applicable in MM disease modeling and cell-based therapies.
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