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There is still a scarcity of data on causes of long-term mortality in patients with venous thromboembolism (VTE).The COMMAND VTE Registry is a physician-initiated, retrospective, multicenter cohort study in which consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan were included between January 2010 and August 2014. We investigated detailed causes and risk factors for long-term mortality.During a median observation period of 1218 days, a total of 764 patients died, and the prevalence of active cancer was higher in patients who died than in patients alive (61 % versus 10 %, P 0.001). The cumulative incidences of cardiac death, pulmonary embolism (PE)-related death, bleeding death, cancer death, and non-cardiovascular non-cancer death were 2.2 %, 2.9 %, 2.0 %, 16.1 %, and 6.7 % at 5 years, respectively. The incidence of cancer death increased gradually, which was the most common cause of long-term death. Among patients without active cancer, the incidence of PE-related death increased rapidly and became a plateau beyond the acute phase, whereas the incidence of non-cardiovascular non-cancer death kept increasing, which became most common in the long term. The separate multivariable analysis among patient with and without active cancer identified independent risk factors of all-cause death including a few patient characteristics among patients with active cancer and several patient characteristics among patients without active cancer.Cancer was the most common cause of long-term mortality, while non-cardiovascular non-cancer death became most common among patients without active cancer.

Introduction: Autologous hematopoietic stem cell transplantation (ASCT) is a well-established treatment for patients with multiple myeloma (MM), and adequate stem cell collection must be assured before ASCT. However, prediction of poor mobilizers (PMs) is still difficult despite several risk factors for mobilization failure having been identified. Methods: We retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan who underwent stem cell collection between October 2006 and August 2020. A CD34+ cell collection of 6 cells/kg was defined as a mobilization failure. The primary endpoint was mobilization failure. The secondary endpoint was overall survival (OS). Odds ratios (ORs) and 95% confidence intervals (CIs) for mobilization failure were calculated using a logistic regression model. The cumulative incidence of mortality was estimated using the Kaplan-Meier method. Results: In the multivariate analysis, absolute monocyte count p = 0.009), platelet count p = 0.001) before mobilization, and time interval from diagnosis to stem cell harvest ≥180 days (adjusted OR 7.69, 95% CI: 1.61–36.87, p = 0.011) were risk factors for PMs. PM patients had poorer OS compared to patients with successful stem cell collection in the univariate analysis (log-rank test p = 0.027). The predicted probability of PMs was estimated by the multiple logistic regression model with a sensitivity of 84.6% and a specificity of 84.0%. Conclusion: Absolute monocyte count

Background There is a paucity of data on the long-term clinical outcomes according to the severity of pulmonary embolism (PE) at initial diagnosis. Methods The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic venous thromboembolism (VTE). After excluding 1312 patients without PE, the current study population consisted of 1715 patients with PE, who were divided into 3 groups according to the clinical severity; massive PE, sub-massive PE and low-risk PE. Results There were 179 patients (10%) with massive PE, 742 patients (43%) with sub-massive PE, and 794 patients (46%) with low-risk PE. By the landmark analysis at 3 months, the cumulative incidences of recurrent VTE were similar among the 3 groups both within and beyond 3 months (Massive PE: 2.9%, Sub-massive PE: 4.2%, and Low-risk PE: 3.3%, P = 0.61, and 4.3%, 8.8%, and 7.8% at 5 years, P = 0.47, respectively). After adjusting confounders, the risk of massive PE relative to low-risk PE for recurrent VTE beyond 3 months remained insignificant (adjusted HR 0.54, 95% CI: 0.13–1.51, P = 0.27). Patients with massive PE at initial diagnosis more often presented as severe recurrent PE events than those with sub-massive and low-risk PE. Conclusions In the current real-world large registry, the long-term risk of overall recurrent VTE in patients with massive PE at initial diagnosis did not significantly differ from those with sub-massive and low-risk PE beyond 3 months, although patients with massive PE at initial diagnosis more frequently developed recurrent VTE as PE with severe clinical presentation.

Anticoagulation therapy is prescribed for the prevention of recurrence in patients with venous thromboembolism, which could be temporarily interrupted during invasive procedures. The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We identified patients who underwent invasive procedures during the entire follow-up period and evaluated periprocedural managements and clinical outcomes at 30 days after invasive procedures. During a median follow-up period of 1213 (IQR: 847–1764) days, 518 patients underwent invasive procedures with the cumulative incidences of 5.8% at 3 months, 11.1% at 1 year, and 24.0% at 5 years. Among 382 patients in high bleeding-risk category of invasive procedures, anticoagulation therapy had been discontinued already in 62 patients (16%) and interrupted temporarily in 288 patients (75%) during the invasive procedures with bridging anticoagulation therapy with heparin in 214 patients (56%). Among 80 patients in low bleeding-risk category, anticoagulation therapy had been already discontinued in 15 patients (19%) and interrupted temporarily in 31 patients (39%) during invasive procedure with bridging anticoagulation therapy with heparin in 17 patients (21%). At 30 days after the invasive procedures, 14 patients (2.7%) experienced recurrent VTE, while 28 patients (5.4%) had major bleeding. This study elucidated the real-world features of peri-procedural management and prognosis in patients with VTE who underwent invasive procedures during follow-up in the large multicenter VTE registry. The 30-day incidence rates of recurrent VTE and major bleeding events were 2.7% and 5.4%.

Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous group of hyperinflammatory statuses that are difficult to diagnose and can be life-threatening. Bone marrow (BM) hemophagocytosis is one of the diagnostic criteria according to HLH 2004 diagnostic criteria and HS score. Limited studies have focused on the prognostic factors of BM hemophagocytosis and its association with hematologic malignancies. We aimed to analyze the clinical significance of BM hemophagocytosis. Patients with BM hemophagocytosis, either by cytology or pathology, were enrolled at Taipei Veterans General Hospital from January 2002 to July 2021. Relevant clinical and laboratory data were extracted from medical records. Of 119 patients with BM hemophagocytosis, 57 were diagnosed with hematologic malignancies. The median age of the patients was 58, ranging from 21 to 90. Splenomegaly (adjusted odds ratio [aOR] 2.96; 95% confidence interval [CI] 1.13-7.79) was a risk factor for hematologic malignancies, while autoimmune disease (aOR 0.07; 95% CI 0.01-0.39) and increased D-dimer (aOR 0.25; 95% CI 0.07-0.92) were protective factors. Risk factors for mortality in patients with BM hemophagocytosis were hematologic malignancies (adjusted hazard ratio [aHR] 2.34; 95% CI 1.24-4.44), Eastern Cooperative Oncology Group score ≥3 (aHR 2.42; 95% CI 1.20-4.89) and thrombocytopenia (aHR 3.09; 95% CI 1.04-9.16). In conclusion, among patients with BM hemophagocytosis, splenomegaly was a predictor of hematologic malignancies. Patients with hematologic malignancies, poor performance status, or thrombocytopenia had a higher mortality risk. Further validation studies are warranted.

Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed to identify risk factors of VTE recurrence and major bleeding in intermediate-risk patients. The COMMAND VTE Registry is a multicenter registry enrolled consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97–14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56–7.50), while the independent risk factors for major bleeding were age ≥ 75 years (HR 2.04, 95% CI 1.36–3.07), men (HR 1.52, 95% CI 1.02–2.27), history of major bleeding (HR 3.48, 95% CI 1.82–6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04–6.37). Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. Unique identifier: UMIN000021132. COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm .

Autologous stem cell transplantation (ASCT) continues to be the standard treatment for transplant-eligible multiple myeloma (MM) patients. A portion of MM patients received ASCT in an isolation room with high-efficiency particulate air (HEPA) filtration. The effectiveness of the HEPA filtration on reducing treatment-related mortality (TRM) is controversial. We enrolled patients with newly diagnosed MM in Taiwan between 2000 and 2017. The primary endpoint of the study was TRM, which was defined as death within 100 days after ASCT. A total of 961 MM patients received ASCT. Of them, 480 patients (49.9%) received ASCT in an isolation room with HEPA filtration (HEPA group). The median overall survival from ASCT was 7.52 years for the HEPA group and 5.88 years for the remaining patients (non-HEPA group) (p = 0.370). The 100-day mortality rate was 1.5% and 1.0% for the HEPA and non-HEPA groups, respectively. In the multivariate analysis, the 100-day mortality had no difference between the HEPA and non-HEPA groups (adjusted hazard ratio 1.65, 95% CI 0.52–5.23). The median cost for ASCT inpatient care was $13,777.6 and $6527.6 for the HEPA and non-HEPA groups, respectively (p

Background The majority of acute pulmonary embolism (PE) is caused by thrombus developed from leg veins. However, impact of concomitant deep venous thrombosis (DVT) on clinical outcomes has not been fully evaluated in patients with acute PE. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic venous thromboembolism (VTE) in Japan. The current study population consisted of 655 acute PE patients who underwent lower extremities ultrasound examination at diagnosis for the assessment of concomitant DVT status. Results There were 424 patients with proximal DVT (64.7%), 162 patients with distal DVT (24.7%), and 69 patients with no DVT (10.5%). The cumulative 90-day incidence of all-cause death was higher in proximal DVT patients than in distal DVT and no DVT patients (7.9%, 2.5%, and 1.4%, p = 0.01). Regarding the causes of death, the cumulative 90-day incidence of PE-related death was low, and not significantly different across the 3 groups (1.4%, 0.6%, and 1.7%, p = 0.62). The most frequent cause of death was cancer in proximal and distal DVT patients. There were no significant differences in 90-day rates of recurrent VTE and major bleeding, regardless of the status of concomitant DVT (2.9%, 3.2%, and 2.2%, p = 0.79, and 1.5%, 4.4%, and 4.9%, p = 0.46, respectively). Conclusions Acute PE with proximal DVT at diagnosis was associated with a higher risk for short-term mortality than in patients without DVT, while the risk for short-term mortality was not significantly different between distal DVT patients and patients without DVT.

There is a paucity of data on the influence of low body weight on clinical outcomes in patients with acute venous thromboembolism (VTE).The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2778 patients with available body weight value, who were divided into 2 groups; 1705 patients with lower body weight (≤60 kg) and 1073 patients with higher body weight (60 kg).Patients with lower body weight were older (70.8 versus 60.9 years, P 0.001), and more often women (75% versus 38%, P 0.001), and more often had active cancer (27% versus 19%, P 0.001) than those with higher body weight. The cumulative 5-year incidence of recurrent VTE was not significantly different between the 2 groups (10.6% versus 10.7%, P = 0.51). The cumulative 5-year incidences of major bleeding and all-cause death were significantly higher in patients with lower body weight than in those with higher body weight (14.6% versus 9.6%, P 0.001, and 35.8% versus 19.8%, P 0.001, respectively). The excess adjusted risk of patients with lower body weight relative to those with higher body weight remained significant for major bleeding and all-cause death (HR 1.57, 95%CI: 1.16-2.12, P = 0.003, and HR 1.50, 95%CI: 1.24-1.81, P 0.001, respectively).In the current Japanese real-world registry, there were a high proportion of patients with low body weight, who had a higher risk for major bleeding and mortality without significant excess risk for recurrent VTE.

Multiple myeloma (MM), a clonal plasma cell malignancy, composes around 10% of hematologic malignancies. Though recent advances in treatment have dramatically improved MM survival, some aggressive courses of disease and dismal outcomes still exist. Low body weight, undernutrition, and cachexia are noted at MM diagnosis. We aim to evaluate the impact of low body mass index (BMI) and undernutrition in MM patients. We retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan between January 1, 2006 and October 31, 2018. Being underweight is defined as having a BMI of under 18.5 kg/m2. The patient’s baseline characteristics, including BMI, serum albumin level, and comorbidities, etc., were recorded. The primary endpoint of the study was all-cause mortality. A Cox regression model was used to estimate the risk factors of mortality. A total of 378 newly diagnosed MM patients were enrolled in this study. The median age of the patients was 69. Thirty patients (7.9%) were underweight at diagnosis. The median overall survival was 1.3 years (95% CI 0.3–5.7) and 5.0 years (95% CI 3.1–5.9) for patients with low BMI and for patients with normal or higher BMI, respectively. In the multivariate analysis, low BMI (95% CI 1.07–4.44), ECOG ≥2 (95% CI 1.02–2.89), hypoalbuminemia (95% CI 1.21–4.01), high LDH (95% CI 1.22–3.49), and light chain ratio > 100 (95% CI 1.06–2.77) were independent risk factors of mortality. MM patients who were underweight, with hypoalbuminemia, poor performance status, higher LDH, and light chain ratio > 100 were associated with poor overall survival.

There are uncertainties on the influence of the days of diagnosis in a week (weekends versus weekdays) on clinical outcomes in patients with acute venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT). The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 337 patients diagnosed on weekends and 2690 patients diagnosed on weekdays. We compared the clinical characteristics, management strategies and 30-day outcomes between the 2 groups. The patients diagnosed on weekends more often presented with PE (72% vs. 55%, P

Infection is associated with great morbidity and mortality in patients with multiple myeloma (MM), but evidence for invasive fungal infections (IFIs) is lacking. We aimed to investigate risk factors for IFI in MM patients and to determine its impact on patients’ survival. We retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan between January 2002 and October 2018. MM was diagnosed according to the International Myeloma Working Group criteria. IFI was defined according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. All risk factors of IFI in MM patients were estimated using Cox regression models in the univariate and multivariate analyses. Of the 623 patients recruited, 22 (3.5%) were diagnosed with proven or probable IFI. Light chain disease (adjusted hazard ratio [HR] 6.74, 95% confidence interval [CI] 2.10–21.66), hemoglobin less than 8 g/dl (adjusted HR 3.34, 95% CI 1.32–8.42), serum albumin

Background Although various prognostic models for primary central nervous system lymphoma (PCNSL) have been developed, there is no consensus regarding the optimal prognostic index. We aimed to evaluate potential prognostic factors and construct a novel predictive model for PCNSL patients. Methods We enrolled newly diagnosed PCNSL patients between 2003 and 2015. The primary endpoint was progression‐free survival (PFS), and the secondary endpoint was overall survival (OS). The prognostic factors identified using multivariate Cox proportional hazards models were used to develop a predictive model. We subsequently validated the prognostic model in an independent cohort. We also evaluated the validity of the existing scores: the International Extranodal Lymphoma Study Group (IELSG), the Nottingham/Barcelona (NB), and the Memorial Sloan‐Kettering Cancer Center models (MSKCC). Results We identified 101 patients with newly diagnosed PCNSL at our center. Multivariate analysis showed that age ≥80, deep brain lesions, and ECOG ≥2 were independent risk factors of PFS. Assigning one point for each factor, we constructed a novel prognostic model, the Taipei Score, with four distinct risk groups (0‐3 points). The performances of the Taipei Score in discriminating both PFS and OS in the training cohort were significant, and the score was validated in the external validation cohort. The IELSG, NB and MSKCC models had insufficient discriminative ability for either PFS or OS in both cohorts. Conclusion The Taipei Score is a simple model that discriminates PFS and OS for PCNSL patients. The score may offer disease risk stratification and facilitate clinical decision‐making., Age, performance status, and deep brain lesions were associated with primary central nervous system lymphoma (PCNSL) survival. The Taipei Score could offer disease risk stratification for PCNSL.

Background The simplified Pulmonary Embolism Severity Index (sPESI) score is a practical score for identification of patients with low-risk pulmonary embolism (PE), although it has not been applied in patients with active cancer. The current study aimed to evaluate the usefulness of the sPESI score in patients with PE and active cancer. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive patients with acute symptomatic VTE. The current study population consisted of 368 patients with PE and active cancer. The 30-day clinical outcomes were compared between patients with sPESI score = 1 and patients with sPESI scores ≥ 2. Results Overall, 37 patients (10%) died during the 30 days after diagnosis. The cumulative 30-day incidences of mortality, and PE-related death, were lower in patients with sPESI score = 1 than in patients with sPESI scores ≥ 2 (6.3% vs 13.1%; log-rank P = .03; and 0.7% vs 3.9%; log-rank P = .046). Among patients with sPESI score = 1, the predominant cause of death was cancer. There were no significant differences in the cumulative 30-day incidence of recurrent VTE and major bleeding between the two groups (3.9% vs 5.6%; log-rank P = .46; and 6.4% vs 4.5%; log-rank P = .45). Conclusions Among patients with PE and active cancer, patients with sPESI score = 1 had a lower 30-day mortality rate compared with patients with sPESI scores ≥ 2, and they showed very low PE-related mortality risk, although the overall mortality rate remained high because of cancer-related mortality. They also showed relatively high risks for recurrence and major bleeding, suggesting the need for careful follow-up. Trial Registry UMIN Clinical Trials Registry; No.: UMIN000021132; URL: http://www.umin.ac.jp/ctr/index.htm

Vitamin K antagonist (VKA) remains an essential option for venous thromboembolism (VTE), although direct oral anticoagulants have become available. However, there is a paucity of data on the optimal intensity and quality of control for VKA in Japanese.The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1938 patients who received VKA with prothrombin time-international normalized ratio (PT-INR) measurement5 times. The primary outcome measure was a composite of symptomatic VTE recurrence or major bleeding at 1 year. The presumed optimal quality of VKA therapy was defined as the combination of PT-INR range and time in therapeutic range (TTR) with the numerically lowest event rate.The group with TTR ≥70 % based on PT-INR range ≥1.5 and2.0 showed the lowest cumulative incidence rate. The cumulative 1-year incidence and the adjusted risk for the primary outcome measure were significantly lower in the optimal quality group than in the non-optimal quality group (5.2 % vs. 11.7 %, p = 0.001, and HR 0.49, 95%CI 0.28-0.81). Similarly, the cumulative 1-year incidences of a recurrent VTE, major bleeding, and all-cause death were significantly lower in the optimal quality group (recurrent VTE: 2.5 % vs. 6.0 %, p = 0.02; major bleeding: 2.8 % vs. 7.0 %, p = 0.008; and all-cause death: 2.8 % vs. 12.6 %, p 0.0001). The lower risk of the optimal quality group relative to non-optimal quality group for the clinical outcomes was consistent regardless of the etiology of VTE (active cancer, transient risk factor, and unprovoked).The current VTE registry showed the optimal intensity of VKA therapy was target PT-INR range ≥1.5 and2.0, which could support the current Japanese guideline recommendation, and the good quality of control for VKA therapy of TTR ≥70 % was independently associated with better outcomes.

Background: Rapid and accurate diagnosis of acute coronary syndrome (ACS) is critical to prevent the fatal complication accompanied with the delay of the treatment. However, the diagnosis of non-ST-segment elevation ACS (NSTE-ACS), especially shortly after the onset, is not straightforward because even high-sensitivity cardiac troponin (hs-cTn) is sometimes not elevated at that phase. We previously reported in a retrospective study that serum nardilysin is a potential biomarker for the early detection of NSTE-ACS. Here, we present the results of the Nardi-ACS study, a multicenter prospective study conducted at six centers in Japan to clarify the significance of nardilysin for the early detection of ACS. Methods and Results: We analyzed serum nardilysin and hs-cTnI (Architect; Abbott) in the sequential 2 independent cohorts; phase I primary cohort (435 patients with chest pain who consecutively visited to the emergency room (ER)) and phase II validation cohort (486 patients with a strong suspicion of ACS who underwent coronary angiography). The frequency of non-ACS, STEMI and NSTE-ACS was 64.4, 22.5, and 13.1 (%) in the phase I, and 14.0, 60.0, and 25.9 (%) in the phase II cohort, respectively. The cutoff value of serum nardilysin was set at 1350.9 pg/ml (mean +2SD) obtained in 246 healthy volunteers, while the cutoff of hs-cTnI was set at 52 pg/ml. The initial blood test in the phase I cohort revealed that nardilysin was significantly elevated in ACS patients, compared to non-ACS patients (p Conclusion: Nardilysin could be a potential biomarker for the early diagnosis of troponin-negative NSTE-ACS.

The composition of the Cr27Fe24Co18Ni26Nb5 high-entropy alloy was selected from the FCC phase in a CrFeCoNiNb alloy. The alloy was melted in an argon atmosphere arc-furnace, followed by annealing in an air furnace. The dendrites of the alloy were in the FCC phase, and the eutectic interdendrites of the alloy comprised HCP and FCC phases. The microstructures and hardness of this alloy were examined, the results indicated that this alloy was very stable. This microstructure and hardness of the alloy almost remained the same after annealing at 1000 °C for 24 h. The polarization behaviors of Cr27Fe24Co18Ni26Nb5 alloy in 1 N sulfuric acid and 1 N hydrochloric acid solutions were measured. Both the corrosion potential and the corrosion current density of the Cr27Fe24Co18Ni26Nb5 alloy increased with increasing test temperatures. The activation energies of the Cr27Fe24Co18Ni26Nb5 alloy in these two solutions were also calculated.

The present work studied the microstructures of Cr19Fe22Co21Ni25Mo13 alloy, and tested the polarization properties in deaerated 1M nitric acid and 1M hydrochloric solutions at different temperatures. The alloy was processed by an argon atmosphere arc-melting. Results indicated that the microstructure of Cr19Fe22Co21Ni25Mo13 alloy was a dendritic one. The dendrites of Cr19Fe22Co21Ni25Mo13 alloy were an FCC structure, and the interdendrites of Cr19Fe22Co21Ni25Mo13 alloy were a eutectic structure with two phases of FCC and simple cubic (SC). The Cr19Fe22Co21Ni25Mo13 alloy had better corrosion resistance compared with commercial 304 stainless steel in both deaerated 1M HNO3 and 1M HCl solutions. The corrosion types of Cr19Fe22Co21Ni25Mo13 alloy in both of 1M HNO3 and 1M HCl solutions were uniform corrosion.

Background Acute myeloid leukemia (AML) is a common hematologic neoplasm with high incidence and mortality in the elderly. Our aims were to explore risk factors for early mortality in elderly AML patients and develop a new prognostic score. Methods We enrolled newly diagnosed AML patients age 60 and above at Taipei Veterans General Hospital between July 2008 and May 2017. The primary endpoint was early mortality, defined as death within two months after AML diagnosis. A multivariate Cox proportional hazards model was used to build a risk‐scoring system incorporating significant risk factors for AML. Results The final cohort included 277 elderly AML patients. The median age was 74 (range 60‐96), and 61.7% were male. The two‐month mortality rate was 29.9%. Age ≥ 80 (adjusted HR 1.88), myocardial infarction (adjusted HR 1.87), ECOG ≥ 2 (adjusted HR 2.10), complex karyotype (adjusted HR 3.21), bone marrow blasts ≥ 70% (adjusted HR 1.88), WBC ≥ 100 × 109/L (adjusted HR 3.31), and estimated glomerular filtration rate (eGFR), Age ≥ 80, myocardial infarction, ECOG ≥ 2, complex karyotype, BM blasts ≥ 70%, WBC ≥ 100 × 109/L, and eGFR

The duration of anticoagulation therapy after venous thromboembolism (VTE) should be based on the balance between risks of recurrent VTE and bleeding. However, there is uncertainty about the impact of these events on subsequent mortality.We evaluated the association of recurrent VTE and major bleeding events with mortality among 3026 patients in the COMMAND VTE Registry. We estimated the risks of the recurrent VTE events and the major bleeding events for subsequent mortality by the time-updated multivariable Cox proportional hazard model.During the median follow-up period of 1218 days, 225 patients developed recurrent VTE events, 274 patients developed major bleeding events, and 763 patients died. The multivariable Cox proportional hazard model revealed that both the recurrent VTE and major bleeding events were strongly associated with subsequent mortality risk (recurrent VTE: HR 3.24, 95%CI 2.57-4.08, P 0.001; major bleeding: HR 3.53, 95%CI 2.88-4.31, P 0.001). Both the recurrent pulmonary embolism (PE) and recurrent deep vein thrombosis (DVT) events were associated with subsequent mortality risk (recurrent PE events: HR 4.42, 95%CI 3.28-5.95, P 0.001; recurrent DVT events: HR 2.42, 95%CI 1.75-3.36, P 0.001).In the real-world patients with VTE, both the recurrent VTE events and the major bleeding events were strongly associated with subsequent mortality risk with the comparable effect size. The recurrent PE and recurrent DVT events were also associated with increased risks for mortality, although the magnitude of the effect on mortality was numerically greater with the recurrent PE events than with the recurrent DVT events.

The relationship between D-dimer level at diagnosis and long-term clinical outcomes has not been fully evaluated in venous thromboembolism (VTE). The COMMAND VTE Registry is a multicenter registry enrolling consecutive acute symptomatic VTE patients in Japan. Patients with available D-dimer levels at diagnosis (N = 2852) were divided into 4 groups according to the D-dimer levels; Quartile 1 (0.0–4.9 µg/mL): N = 682, Quartile 2 (5.0–9.9 µg/mL) N = 694, Quartile 3 (10.0–19.9 µg/mL) N = 710, and Quartile 4 (≥ 20.0 µg/mL): N = 766. The cumulative incidence of all-cause death was higher in Quartile 4 throughout the entire follow-up period (19.9%, 24.9%, 28.8%, and 41.5% at 5-year, P

Background There are limited data assessing the risk for bleeding on anticoagulation therapy beyond the acute phase in patients with venous thromboembolism (VTE). The present study aimed to identify risk factors for major bleeding during prolonged anticoagulation therapy in VTE patients. Patients and Methods The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2,728 patients who received anticoagulation therapy beyond the acute phase, after excluding those patients with major bleeding events (n = 48), death (n = 66), or loss to follow-up (n = 32) during the initial parenteral anticoagulation period within 10 days after diagnosis, and those without anticoagulation therapy beyond 10 days after diagnosis (n = 153). Results During the median follow-up period of 555 days, major bleeding occurred in 189 patients (70 patients within 3 months; 119 patients beyond 3 months) with fatal bleeding in 24 patients (13%). The cumulative incidence of major bleeding was 2.7% at 3 months, 5.2% at 1 year, and 11.8% at 5 years. Active cancer (hazard ratio [HR], 3.06, 95% confidence interval [CI], 2.23–4.18), previous major bleeding (HR, 2.38, 95% CI, 1.51–3.59), anemia (HR, 1.75, 95% CI, 1.27–2.43), thrombocytopenia (HR, 2.11, 95% CI, 1.27–3.33), and age ≥75 years (HR, 1.64, 95% CI, 1.22–2.20) were independently associated with an increased risk for major bleeding by the multivariable Cox regression model. Conclusion Major bleeding events were not uncommon during prolonged anticoagulation therapy in real-world VTE patients. Active cancer, previous major bleeding, anemia, thrombocytopenia, and old age were the independent risk factors for major bleeding.

BACKGROUND Differences in the clinical characteristics and outcomes of venous thromboembolisms (VTEs) based on different clinical situations surrounding the onset might be important for directing appropriate treatment strategies, but have not yet been appropriately evaluated. Methods and Results: The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTEs in Japan between January 2010 and August 2014. We divided the study population into 3 groups: Out-of-hospital onset (n=2,308), In-hospital onset with recent surgery (n=310), and In-hospital onset without recent surgery (n=374). Active cancer was most prevalent in the In-hospital onset without recent surgery group, and least in the Out-of-hospital onset group (Out-of-hospital onset group: 20%, In-hospital onset with recent surgery group: 26%, and In-hospital onset without recent surgery group: 38%, P

Anticoagulation therapy is prescribed for the prevention of recurrence in patients with venous thromboembolism, which could be temporarily interrupted during invasive procedures. The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We identified patients who underwent invasive procedures during the entire follow-up period and evaluated periprocedural managements and clinical outcomes at 30 days after invasive procedures. During a median follow-up period of 1213 (IQR: 847-1764) days, 518 patients underwent invasive procedures with the cumulative incidences of 5.8% at 3 months, 11.1% at 1 year, and 24.0% at 5 years. Among 382 patients in high bleeding-risk category of invasive procedures, anticoagulation therapy had been discontinued already in 62 patients (16%) and interrupted temporarily in 288 patients (75%) during the invasive procedures with bridging anticoagulation therapy with heparin in 214 patients (56%). Among 80 patients in low bleeding-risk category, anticoagulation therapy had been already discontinued in 15 patients (19%) and interrupted temporarily in 31 patients (39%) during invasive procedure with bridging anticoagulation therapy with heparin in 17 patients (21%). At 30 days after the invasive procedures, 14 patients (2.7%) experienced recurrent VTE, while 28 patients (5.4%) had major bleeding. This study elucidated the real-world features of peri-procedural management and prognosis in patients with VTE who underwent invasive procedures during follow-up in the large multicenter VTE registry. The 30-day incidence rates of recurrent VTE and major bleeding events were 2.7% and 5.4%.

BACKGROUND Patients with cancer-associated venous thromboembolism (VTE) are at high risk for recurrent VTE and are recommended to receive prolonged anticoagulation therapy if they are at a low risk for bleeding. However, there are no established risk factors for bleeding during anticoagulation therapy.Methods and Results:The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3,027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 592 cancer-associated VTE patients with anticoagulation therapy. We constructed a multivariable Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the potential risk factors for major bleeding. During a median follow-up period of 199 days, major bleeding occurred in 72 patients. The cumulative incidence of major bleeding was 5.8% at 3 months, 13.8% at 1 year, 17.5% at 2 years, and 28.1% at 5 years. The most frequent major bleeding site was gastrointestinal tract (47%). Terminal cancer (adjusted HR, 4.17; 95% CI, 2.22-7.85, P

Multiple myeloma (MM), a clonal plasma cell malignancy, composes around 10% of hematologic malignancies. Though recent advances in treatment have dramatically improved MM survival, some aggressive courses of disease and dismal outcomes still exist. Low body weight, undernutrition, and cachexia are noted at MM diagnosis. We aim to evaluate the impact of low body mass index (BMI) and undernutrition in MM patients.We retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan between January 1, 2006 and October 31, 2018. Being underweight is defined as having a BMI of under 18.5 kg/mA total of 378 newly diagnosed MM patients were enrolled in this study. The median age of the patients was 69. Thirty patients (7.9%) were underweight at diagnosis. The median overall survival was 1.3 years (95% CI 0.3-5.7) and 5.0 years (95% CI 3.1-5.9) for patients with low BMI and for patients with normal or higher BMI, respectively. In the multivariate analysis, low BMI (95% CI 1.07-4.44), ECOG ≥2 (95% CI 1.02-2.89), hypoalbuminemia (95% CI 1.21-4.01), high LDH (95% CI 1.22-3.49), and light chain ratio 100 (95% CI 1.06-2.77) were independent risk factors of mortality.MM patients who were underweight, with hypoalbuminemia, poor performance status, higher LDH, and light chain ratio 100 were associated with poor overall survival.

Background: Overall survival of patients with primary CNS lymphoma (PCNSL) has improved since the introduction of immunochemotherapy. However, up to 10-15% of PCNSL patients still die shortly after diagnosis. In the present study, we aimed to investigate the risk factors of early mortality (death within 60 days after diagnosis) in patients with PCNSL. Methods: We included newly diagnosed PCNSL patients in a tertiary medical center in Taiwan between January 1, 2002 and May 31, 2018. Clinical risk factors were collected and compared between PCNSL patients who had and did not have early mortality. Results: A total of 133 consecutive patients with PCNSL were included in this study. Approximately 9.8% of the PCNSL patients had early mortality. In multivariate analysis, age ≥ 80 (adjusted hazard ratio [HR] 3.34, 95% confidence interval [CI] 1.01-11.04, p = 0.048) and involvement of the basal ganglia (adjusted HR 4.85, 95% CI 1.47-15.95, p = 0.009) were identified as independent risk factors of early mortality. Use of MTX-based chemotherapy served as an independent protective factor for early mortality (adjusted HR 0.19, 95% CI 0.05-0.67, p = 0.010). Infection and tumor-associated mass effect contributed most to early mortality. Conclusion: Early mortality is not uncommon in patients with PCNSL. Identification of patients with higher risk may help clinicians with initiating appropriate surveillance and management.

Introduction The external validation of the modified Ottawa score to predict the risk of recurrence in patients with cancer-associated venous thromboembolism (VTE) has not yet been firmly established. The present study aimed to evaluate the utility and limitations of the modified Ottawa score in the risk stratification of recurrent VTE in patients with cancer-associated VTE. Materials and methods The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 614 cancer-associated VTE patients, who were divided into 3 groups; High-risk group: 202 patients (33%) with a modified Ottawa score ≥ 1, Intermediate-risk group: 269 patients (44%) with a score = 0, and Low-risk group: 143 patients (23%) with a score ≤ −1. Results Recurrent VTE occurred in 39 patients on anticoagulation therapy within 6 months. The cumulative incidence of recurrent VTE substantially increased in the higher risk categories by the modified Ottawa score (high-risk group: 13.6% [95%CI, 8.9%–20.2%], intermediate-risk group: 5.9% [95%CI, 3.5%–9.8%], and low-risk group: 3.0% [95%CI, 1.1%–7.8%], P = .02). The discriminating power of the score was modest with a C-statistic of 0.63. Each score component of the score had a different impact on recurrent events with a variable effect size. Conclusions The risks of recurrence in patients with cancer-associated VTE substantially increased in the higher risk categories by using the modified Ottawa score, but the discriminating power of the score for recurrence was modest with a variable impact of each score component on recurrent events.

Background: The simplified pulmonary embolism severity index (sPESI) score has been reported to be useful in predicting 30-day mortality for patients with pulmonary embolism, which helps the identification of low-risk patients for early hospital discharge or home treatment. However, therapeutic decision-making should also be based on the risks of adverse events other than mortality. Methods: The COMMAND VTE Registry is a multicentre registry enrolling consecutive patients with acute symptomatic venous thromboembolism in Japan between January 2010 and August 2014, and the current study population consisted of 1715 patients with pulmonary embolism. We calculated the sPESI score for each patient, and compared 30-day rates of mortality, recurrent venous thromboembolism and major bleeding between sPESI scores of 0 and 1 or greater. Results: Patients with a sPESI score of 0 accounted for 383 (22%) patients, and 110 (6.4%) patients died within 30 days. The cumulative 30-day incidence of mortality was lower in patients with a sPESI score of 0 than those with a sPESI score of 1 or greater (0.5% vs. 8.1%, log rank PConclusions: In patients with a sPESI score of 0, the 30-day mortality, recurrent venous thromboembolism and major bleeding rates were reasonably low. The sPESI score could be useful to identify candidates for early hospital discharge or home treatment.

Transient ischemic attack (TIA) is a predictor for cerebral infarction (CI), and early diagnosis of TIA is extremely important for the prevention of CI. We set out to identify novel antibody biomarkers for TIA and CI, and detected matrix metalloproteinase 1 (MMP1), chromobox homolog 1 (CBX1), and chromobox homolog 5 (CBX5) as candidate antigens using serological identification of antigens by recombinant cDNA expression cloning (SEREX) and Western blotting to confirm the presence of serum antibodies against the antigens. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) revealed that serum antibody levels were significantly higher in patients with TIA or acute-phase CI (aCI) compared with healthy donors (P < 0.01). Spearman’s correlation analysis and multivariate logistic regression analysis demonstrated that levels of anti-MMP1, anti-CBX1, and anti-CBX5 antibodies were associated with age, cigarette-smoking habits, and blood pressure. Thus, serum levels of antibodies against MMP1, CBX1, and CBX5 could potentially serve as useful tools for diagnosing TIA and predicting the onset of aCI.