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BackgroundThe mortality rate of acute coronary syndrome (ACS) remains high. Therefore, patients with ACS should undergo early risk stratification, for which various risk calculation tools are available. However, it remains uncertain whether the predictive performance varies over time between risk calculation tools for different target periods. This study aimed to compare the predictive performance of risk calculation tools in estimating short- and long-term mortality risks in patients with ACS, while considering different observation periods using time-dependent receiver operating characteristic (ROC) analysis.MethodsThis study included 404 consecutive patients with ACS who underwent coronary angiography at our hospital from March 2017 to January 2021. The ACTION and GRACE scores for short-term risk stratification purposes and CRUSADE scores for long-term risk stratification purposes were calculated for all participants. The participants were followed up for 36 months to assess mortality. Using time-dependent ROC analysis, we evaluated the area under the curve (AUC) of the ACTION, CRUSADE, and GRACE scores at 1, 6, 12, 24, and 36 months.ResultsSixty-six patients died during the observation periods. The AUCs at 1, 6, 12, 24, and 36 months of the ACTION score were 0.942, 0.925, 0.889, 0.856, and 0.832; those of the CRUSADE score were 0.881, 0.883, 0.862, 0.876, and 0.862; and those of the GRACE score 0.949, 0.928, 0.888, 0.875, and 0.860, respectively.ConclusionsThe ACTION and GRACE scores were excellent risk stratification tools for mortality in the short term. The prognostic performance of each risk score was almost similar in the long term, but the CRUSADE score might be a superior risk stratification tool in the longer term than 3 years.

Metabolic pathways are plastic and rapidly change in response to stress or perturbation. Current metabolic profiling techniques require lysis of many cells, complicating the tracking of metabolic changes over time after stress in rare cells such as hematopoietic stem cells (HSCs). Here, we aimed to identify the key metabolic enzymes that define differences in glycolytic metabolism between steady-state and stress conditions in murine HSCs and elucidate their regulatory mechanisms. Through quantitative 13C metabolic flux analysis of glucose metabolism using high-sensitivity glucose tracing and mathematical modeling, we found that HSCs activate the glycolytic rate-limiting enzyme phosphofructokinase (PFK) during proliferation and oxidative phosphorylation (OXPHOS) inhibition. Real-time measurement of ATP levels in single HSCs demonstrated that proliferative stress or OXPHOS inhibition led to accelerated glycolysis via increased activity of PFKFB3, the enzyme regulating an allosteric PFK activator, within seconds to meet ATP requirements. Furthermore, varying stresses differentially activated PFKFB3 via PRMT1-dependent methylation during proliferative stress and via AMPK-dependent phosphorylation during OXPHOS inhibition. Overexpression of Pfkfb3 induced HSC proliferation and promoted differentiated cell production, whereas inhibition or loss of Pfkfb3 suppressed them. This study reveals the flexible and multilayered regulation of HSC glycolytic metabolism to sustain hematopoiesis under stress and provides techniques to better understand the physiological metabolism of rare hematopoietic cells.

An 89-year-old man with a history of percutaneous coronary intervention using a sirolimus-eluting stent presented with recurrent in-stent occlusion. Pathological assessment of the neointima resected via directional coronary atherectomy revealed a double-layered thrombus. Clopidogrel resistance and limited antithrombotic regimen owing to high bleeding risk likely resulted in the in-stent thrombotic occlusion.

ALE-1, a micro-satellite created for the demonstration of artificial shooting stars, required orbital descent before mission execution due to safety aspects in orbit. ALE-1 utilized a drag sail called SDOM (Separable De-Orbit Mechanism) for a passive de-orbit maneuver, which was successfully completed, lowering the orbit from about 500 km down to about 400 km. This paper summarizes the detailed history of satellite operation and the results of the de-orbit maneuver demonstration during the past three years. Although the SDOM sail faced difficulty in keeping the desired deployed shape of the drag sail due to mechanical troubles, by letting the sail be a drag flag instead, it could still deliver a meaningful de-orbit performance to allow the satellite to successfully lower the orbit as planned. The de-orbit effect of the drag flag was evaluated using comparisons between orbit propagation simulations and the actual orbit transition flight data provided in the form of TLE (Two-Line Element) sets. Through this study, it is demonstrated that the SDOM can provide orbit transfer capabilities for satellites. Furthermore, the de-orbit performance of the drag flag can be evaluated, which could be an important reference for the future implementation of de-orbit devices to solve space debris problems.

Objective: The combination of endovenous therapies with stab avulsion or ultrasound guided foam sclerotherapy is widely performed. However, these conventional techniques tend to result in incomplete avulsions or persistent varicosities. Methods: One hundred and thirteen legs in 97 consecutive patients who underwent 1470 nm laser ablation for great saphenous varicose veins were enrolled. The foam sclerosing agent was injected via the sheath after endovenous laser ablation (EVLA). Patients were divided into two groups: EVLA only group (Control; n = 50) and EVLA and transluminal injection of foam sclerotherapy (TLFS) group (SCL; n = 63). Results: At three month follow up, reflux was abolished throughout all treated great saphenous veins (GSVs) when assessed with Duplex ultrasound. Thrombophlebitis was observed in two patients in the SCL group (p = .13). Additional second stage sclerotherapy was needed in the Control group (n = 33, 66%) vs. SCL group (n = 2, 3%; p < .0001). The venous clinical severity score (VCSS) was significantly improved in the SCL group (changes of VCSS, Control −3.3 ± 1.7 and SCL -4.4 ± 1.0; p < .0001). Univariable and multivariable analyses revealed that, among age, sex, Clinical-Etiology-Anatomy-Pathophysiology classification, linear endovenous energy density, and TLFS, TLFS was the only significant factor of improved VCSS (hazard ratio = −0.96; 95% confidence interval = −1.4 to −0.58; p < .0001). Conclusions: TLFS combined with EVLA may be an easy, safe, and effective procedure with acceptable complications vs. EVLA alone and reduces additional second stage interventions.

Recurrent varicose veins are considered to be caused by the recurrence of reflux but rarely may be secondary to other pathologies. A 39-year-old man complained of right lower leg skin pigmentation, pain and fatigue for several years. Duplex ultrasound revealed that the great saphenous vein diameter at the saphenofemoral junction level was 7.7 cm, and at the knee medial level was 14.4 cm. The reflux time at the proximal great saphenousvein level was 1.85 s. Endovenous laser ablation for dilated and refluxed great saphenous vein was performed. However, 1 year later, the symptoms recurred. Duplex ultrasound suspected abnormal arterial flow from the right superficial femoral artery to the recanalized segment of previously ablated great saphenous vein and anterior accessory saphenous vein. One month later, despite the successful re-endovenous laser ablation, the symptoms recurred. Computed tomography angiography showed three fistulous vessels from superficial femoral artery to anterior accessory saphenous vein. Combined treatments with endovenous laser ablation and coil embolization was performed. Ultimately, the fistulas were obliterated and the patient remained free of symptoms. Varicose veins due to the fistulas from superficial femoral artery are rare and difficult to diagnose but can be entirely treated with the percutaneous approach.

A 49-year-old woman diagnosed with chronic myeloid leukemia in the chronic phase was started on dasatinib treatment, after which she complained of myodesopsia. Nineteen months after diagnosis, the patient again complained of myodesopsia and developed bilateral optic neuritis. Cerebrospinal fluid analysis revealed an increase in blasts, although peripheral blood and bone marrow examination confirmed that the patient remained in a molecular response to tyrosine kinase inhibitor (TKI) therapy. The patient was diagnosed with an isolated central nervous system blast crisis, a rare occurrence with second-generation TKI therapy, and the initial presentation of myodesopsia represented a symptom of this condition. Keywords: Chronic myeloid leukemia, Tyrosine kinase inhibitor, Central nervous system, Blast crisis, Myodesopsia

Background: Although eltrombopag has recently been approved for treating AA, the effects of its clinical use remain unknown. Methods: We retrospectively analyzed 11 patients with AA, who had been treated with eltrombopag from August 2017 to May 2018. Results: Overall response rate was 55%. There was tri-lineage recovery in four patients and platelet recovery in two. The reactive time was within 8 weeks after treatment initiation. Stage at the initial assessment, the neutrophil-to-lymphocyte ratio and platelet counts were significantly different between the responders and non-responders. Conclusion: Eltrombopag is a promising agent for treating patients with any degree of AA. Keywords: Eltrombopag, Aplastic anemia, Neutrophil-to-lymphocyte ratio, Real-world setting

The survival of multiple myeloma patients has improved significantly over the last several decades. However, the median overall survival of these patients remains less than 5 years. In this report, we discuss 4 cases of multiple myeloma patients that showed long survival. Interestingly, these patients had severe organ damage at diagnosis, used only conventional agents, and did not always show deep response. Although current guidelines recommend novel agents to achieve deep response, the current cases suggest that some multiple myeloma patients may not need intensive treatment. Here, we discuss 4 cases of symptomatic but indolent transplant-ineligible myeloma.

Pure red cell aplasia (PRCA) is a rare disorder characterized by marked erythroid hypoplasia with maturation arrest in the bone marrow. Secondary acquired PRCA may be associated with hematologic disorders. A few case reports have described PRCA associated with multiple myeloma (MM). However, the clinical course and mechanism of PRCA associated with MM remain unknown. We herein report two cases of PRCA associated with MM in patients undergoing treatment with lenalidomide. Keywords: Pure red cell aplasia, Multiple myeloma, Lenalidomide

A 63-year-old man was diagnosed with a rare variant of acute promyelocytic leukemia (APL) with t(4;17)(q12; q21) that showed atypical morphological features and two different clinical symptoms. He was started on standard induction chemotherapy for acute myeloid leukemia, which decreased myeloblast numbers; however, APL-like blasts remained. He then received a salvage therapy that added all-trans retinoic acid (ATRA). After ATRA commenced, APL-like blasts disappeared and cytogenetic analysis became normal. However, myeloblasts subsequently increased, and he became resistant. In summary, this patient exhibited two different clinical courses of acute myeloid leukemia and APL.

Background: Neutrophil-to-lymphocyte ratio (NLR) has been recognized as a poor prognostic indicator in various solid tumors. Methods: We retrospectively analyzed 530 patients with de novo DLBCL who were diagnosed from April 2002 to November 2017. Results: The median age of patients was 69 (range, 20–95) years, and 59% were male. The optimal cutoff for NLR was 5.2. NLR (5.2) was not associated with overall and progression free survival. Conclusion: Our study failed to reveal the predictive value of NLR and demonstrated that the NCCN-IPI might be the most powerful predictor in DLBCL. Keywords: Neutrophil-to-lymphocyte ratio, Diffuse large B cell lymphoma, NCCN-IPI

Radiometric calibration utilizing the Moon as a reference source is termed as lunar calibration. It is a useful method for evaluating the performance of optical sensors onboard satellites orbiting the Earth. Lunar calibration provides sufficient radiometric calibration opportunities without requiring any special equipment, and is suitable for nano/microsatellites. This study applies lunar calibration to a multispectral sensor, Ocean Observation Camera (OOC), on board a microsatellite named Rapid International Scientific Experiment Satellite. Simulating the brightness of the Moon based on the RObotic Lunar Observatory and SELENE/Spectrum Profiler models, sensitivity degradation was proven to be negligible in any of the four spectral bands of the OOC with the sensor temperature correction. A bluing trend in the OOC’s sensor sensitivity was revealed, indicating a shorter observation wavelength shows larger irradiance. Comparing the top-of-atmosphere reflectance of Railroad Valley Playa with the Radiometric Calibration Network dataset revealed that the derived calibration parameter from the lunar calibration was valid for correcting the bluing trend in the visible range. Although the lunar and vicarious calibration parameters for the infrared band were unexpectedly inconsistent, lunar calibration could potentially contribute toward estimating the contaminated background radiance in the Earth observation images.

Dasatinib is currently approved for clinical use as a first-line treatment agent for newly diagnosed chronic myeloid leukemia (CML). However, only a few clinical trials have been performed to evaluate dasatinibinduced PE following first-line therapy. We investigated the incidence and clinical features of dasatinib-induced PE following first-line therapy in Japanese CML patients of real world clinical practice settings. Among 22 patients, the median age of PEpositive patients was higher than that of PEnegative patients. Major molecular response was achieved in 75% of PE-positive patients and 50% of PE-negative patients. Most patients developed PE more than 1 year after treatment. Appearance of PE is associated with better clinical response during dasatinib treatment, however it is developed at any time. Elderly and high-risk patients tend to develop PE. The clinical features of dasatinib-induced PE following first-line therapy might be late onset and might not immediately follow the increasing of large granular lymphocyte.

Lenalidomide is an immunomodulating derivative of thalidomide, which shows anti-tumor activity against myeloma cells with immunomodulation including augmentation of T-cell and natural killer cell function. Continuous treatment with this agent shows better survival benefit in patients with multiple myeloma and combined lenalidomide with dexamethasone (LEN-DEX) is a standard treatment regimen. However, fatigue is a frequent symptom resulting from lenalidomide administration. This side-effect therefore reduces quality of life for elderly patients and, furthermore, is a reason for treatment discontinuation. Unfortunately, appropriate preventive countermeasures against lenalidomide-related fatigue have not been established. Ninjin'yoeito is a traditional Chinese medicine made from the extracts of 12 herbal plants, which positively affects immunity and inflammation. It is used to treat fatigue, decreased appetite, anemia, and general malaise associated with malignant tumors and chemotherapy. We have previously reported that ninjin'yoeito significantly improved patients' subjective fatigue symptoms treated with melphalan-prednisone for multiple myeloma. In the present study, we assessed the benefits of ninjin'yoeito as a supplementary treatment for patients with myeloma, and its effect on lenalidomide treatment regime compliance. We retrospectively analyzed 36 cases of newly diagnosed or relapsed/refractory multiple myeloma. The study included patients receiving LEN-DEX with onset of general fatigue after lenalidomide administration (13 and 23 patients with or without ninjin'yoeito, respectively). Frequency of subjective fatigue was significantly decreased in patients administered ninjin'yoeito, compared to those treated with LEN-DEX alone (92.3 and 47.8 % of patients with and without ninjin'yoeito, respectively; p = 0.008). In addition, combined use of ninjin'yoeito and LEN-DEX showed a trend toward reduced rates of treatment discontinuation (7.7 % and 34.8 % of patients with and without ninjin'yoeito, respectively; p = 0.076). Our results suggest that ninjin'yoeito is an effective method for treating subjective fatigue caused by lenalidomide and may have the potential to extend lenalidomide treatment duration.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication of organ transplantation. Progress has recently been made in the pathological classification of PTLD. However, the clinical course has not been clarified because of the rarity of this disease. We experienced a case of PTLD with a fulminant clinical course. The patient had been under longterm immunosuppressive treatment for aplastic anemia. He received related allogeneic hematopoietic stem cell transplantation. Soon after transplantation, he developed PTLD. According to the guidelines, we reduced immunosuppression. However, the disease course was so fulminant that there was no time for the patient to respond, and he died of multi-organ failure. There may be various clinical types of PTLD, which may include some fulminant cases. In such a case, it is not sufficient to reduce immunosuppression. The patient should be carefully observed and an appropriate individual treatment should be chosen.

The correlation between human T-cell leukemia virus type І (HTLV-І) infection and malignant neoplasms other than adult T-cell lymphoma (ATL) remains unknown. We analyzed the frequency of primary malignant neoplasm in HTLV-І-seropositive patients. From January 2006 to December 2016, 203 patients were diagnosed as HTLV-І-seropositive at Kansai Medical University Hospital. Among them, 32 developed a primary malignant neoplasm. Their median age was 64 years old, 63% of them were male, and 69% of them were HTLV-I carriers. This group had the following distribution of ATL subtypes: 31% smoldering type, 0% chronic type, 3% acute type, and 3% lymphoma type. Among them, 53% was hematology malignancy, and solid tumor was 47%. The most frequent type of hematological malignancy was T-cell lymphoma (23%), followed B-cell lymphoma (16%), and myelodysplastic syndromes (6%). The most frequent primary solid tumor locations were the lung (15%), followed by the colon (9%), prostate (6%), kidney (6%), cervix (2%), breast (2%), liver (2%), pancreas (2%), and oral cavity (2%). Our results suggest that HTLV-Іinfection is often associated with the development of other malignant neoplasms. Therefore, HTLV-І-positive patients should be made aware of their increased risk for the onset of a malignant neoplasm and undergo increased surveillance.

To evaluate the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI), we analyzed 284 patients treated with the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in our institution in Japan. Their 5-year overall survival (OS) by risk level was 80.7%, 74.8%, 55.4% and 67.5% (P=0.005); and their 5-year progression-free survival (PFS) was 76.8%, 78.6%, 63.7% and 58.3% (P=0.0722). The NCCN-IPI is a simple scale that uses conventional clinical factors, but did not reflect survival in our cohort. The NCCN-IPI may require further evaluation for different regions and ethnicities before adopting it for routine clinical use.

A 69-year-old man with chronic-phase chronic myeloid leukemia was initially treated with 100 mg dasatinib once a day. Despite a major molecular response within 9 months, he developed hemorrhagic colitis 32 months after starting dasatinib. Colonoscopy identified multiple hemorrhagic ulcers in the transverse colon. The pathological findings indicated cytomegalovirus infection. Dasatinib was stopped and he was started on ganciclovir. Three months later, colonoscopy confirmed the disappearance of the hemorrhagic ulcers. Dasatinib is a second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia. As a multi-kinase inhibitor that acts on SRC-family kinases, its broader off-target kinase-inhibitory activity may account for the adverse events of dasatinib. Although gastrointestinal bleeding is common in patients taking dasatinib, the combination of cytomegalovirus infection and hemorrhagic colitis in the absence of systemic immunodeficiency is rare. Based on this case of dasatinibinduced hemorrhagic colitis with cytomegalovirus infection, we describe a possible mechanism and effective treatment.

The acronym CRAB summarizes the most typical clinical manifestations of multiple myeloma, these being hypercalcemia, renal failure, anemia, and bone disease. CRAB can be used to distinguish between active, symptomatic multiple myeloma and monoclonal gammopathy of undermined significance or smoldering myeloma. The distinction is relevant not only for classification and diagnosis but also for therapy. CRAB factors influence the prognosis of multiple myeloma. However, it is unclear whether the presence of CRAB factors has an influence on the prognosis of myeloma treated with novel agents. In the current study, patients with hypercalcemia and bone disease showed a significantly worse prognosis, whereas anemia and renal failure showed no difference in survival. Novel agents used for treatment of patients with renal failure suggested a favorable outcome compared with conventional therapy. Bone disease was the most common factor and may have the strongest prognostic value in symptomatic myeloma patients using novel agents.

Spontaneous osteonecrosis of the knee (SPONK) usually involves a single condyle, most often the medial femoral condyle (MFC). Involvement of the medial tibial plateau (MTP) is less common, occurring in about 2% of knees with SPONK. Early onset SPONK on the ipsilateral side of the medial compartment is very rare, with, to our knowledge, only four cases reported to date. We describe a very rare case of SPONK with early simultaneous development in the MFC and MTP. Serial plain radiographs and magnetic resonance imaging showed that SPONK in both condyles followed a similar progressive course. The pathological findings in these lesions were similar to those observed in subchondral insufficiency fractures.

In this work, we collect Ramsey-type results concerning rainbow edge colorings of graphs.