Exploratory rivaroxaban trial for isolated calf deep vein thrombosis with a risk factor of thrombosis extension: an open-label, multicenter, randomized controlled trial.

Background: Limited evidence exists regarding the incidence of recurrent venous thromboembolism (VTE) in patients diagnosed with isolated distal deep vein thrombosis (DVT) who are at risk of thrombosis extension whether they receive anticoagulation therapy or not. Objectives: The study aimed to investigate the incidence of recurrent VTE and the impact of rivaroxaban in this patient population. Methods: This open-label, exploratory, and randomized controlled trial was conducted at 7 centers in Japan between April 2019 and April 2022. Adult patients with isolated distal DVT at risk of thrombosis extension received either rivaroxaban combined with physical therapy or physical therapy alone for 90 days. Whole-leg ultrasound was performed at 14 and 90 days. We assessed a composite outcome of symptomatic or asymptomatic proximal DVT or symptomatic pulmonary embolism as the primary outcome until the end of the treatment period using an intention-to-treat analysis. Major bleeding was evaluated as a key secondary outcome. Results: Out of 90 enrolled patients, 3 were excluded due to withdrawal of consent; therefore, we analyzed 87 participants. The rivaroxaban group (n = 42) reported no primary outcomes (0%; 95% CI, 0.0%-8.4%), whereas the physical therapy group (n = 45) had 2 cases of symptomatic proximal DVT (4.4%; 95% CI, 0.5%-15.1%). Major bleeding events occurred in 4 patients in the rivaroxaban group (9.5%; 95% CI, 2.7%-22.6%), whereas no events occurred in the physical therapy group (0%; 95% CI, 0%-7.9%). Conclusion: Preliminary data suggest that rivaroxaban may reduce the risk of VTE recurrence among this patient subset, albeit with an increased incidence of bleeding events.

Risk of recurrent venous thromboembolism and major bleeding according to risk factor profiles in Asian patients: a subgroup analysis EINSTEIN-Extension and EINSTEIN-CHOICE.

BACKGROUND: Risks of recurrence and major bleeding with extended anticoagulation in Asian patients with venous thromboembolism (VTE) are similar to those in non-Asian patients but risks according to baseline risk factor profiles is not well documented. METHODS: Subgroup analysis of two randomized trials, which compared once-daily rivaroxaban (20 mg or 10 mg) with placebo or aspirin (100 mg) for extended treatment in Asian patients with VTE who had completed 6-12 months of anticoagulation. Index events were classified as unprovoked, provoked by major persistent risk factors, minor persistent risk factors, minor transient risk factors, or major transient risk factors. One-year cumulative risks of recurrent VTE were calculated for these risk factor profiles. RESULTS: 367 patients received rivaroxaban, 159 aspirin, and 48 placebo. For patients with unprovoked VTE, one-year cumulative incidences of recurrence in the 202 patients given rivaroxaban, the 89 given aspirin and the 28 given placebo were 1.6%, 5.8%, and 14.8%, respectively. For patients with VTE provoked by minor persistent risk factors, these incidences were 0% in the 74 patients given rivaroxaban, 9.3% in the 36 given aspirin, and 0% in the 12 given placebo. No recurrent VTE occurred in patients with VTE provoked by major persistent or transient risk factors or minor transient risk factors. Rivaroxaban was not associated with a significant increase in major bleeding. CONCLUSIONS: Rivaroxaban seems to be an effective and safe option for extended treatment in Asian patients, especially those presenting with unprovoked VTE. Subgroups of patients with provoked risk factors were too small to draw meaningful conclusions. TRIAL REGISTRATION: NCT00439725 and NCT02064439.

Diagnostic performance of fluoroscopic video analysis for pulmonary embolism: a prospective observational study.

PURPOSE: Dynamic chest radiography using X-ray fluoroscopic video analysis has shown potential for the diagnosis of pulmonary embolism (PE), but its diagnostic performance remains uncertain. We aimed to evaluate the diagnostic performance of fluoroscopic video analysis for diagnosing PE. METHODS: A prospective single-center observational study was conducted between October 2020 and January 2022. Fifty consecutive adult patients, comprising definitive PE, pulmonary hypertension (PH), or suspected PH, were enrolled. The study population was classified into 23 PE and 27 non-PE cases by contrast-enhanced computed tomography, lung scintigraphy, right heart catheterization, and pulmonary angiography. Cineradiographic images of 10-second breath-holds were obtained and analyzed using a fluoroscopic video analysis workstation to generate pulmonary circulation images. Two blinded cardiologists qualitatively assessed the presence or absence of perfusion defects on the pulmonary circulation images. The diagnosis obtained from the fluoroscopic analysis was compared with the definitive diagnosis. The primary outcomes included sensitivity, specificity, positive and negative predictive values, and overall accuracy for diagnosing PE. RESULTS: Perfusion defects were observed in 21 of 23 PE patients and 13 of 27 non-PE patients. The diagnostic performance of fluoroscopic video analysis for diagnosing PE showed a sensitivity of 91%, specificity of 52%, positive predictive value of 62%, negative predictive value of 88%, and overall accuracy of 70%. CONCLUSIONS: The high sensitivity of the fluoroscopic video analysis suggests its potential usefulness in ruling out PE without the need for contrast media or radionuclide; however, its specificity and overall accuracy remain limited.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants for Japanese Patients With Venous Thromboembolism　- The Primary Results From the KUROSIO Study.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended as the first-choice anticoagulation therapy in the acute phase of venous thromboembolism (VTE). However, there is limited real-world data for Japanese VTE patients.Methods and Results: The KUROSIO study (UMIN000023747) was a prospective long-term observational study comprising 1,017 patients with concurrent acute symptomatic pulmonary thromboembolism and proximal deep vein thrombosis (DVT) or isolated calf DVT initially treated with DOACs. After excluding 24 patients, 993 (mean age, 66.3±15.1 years; 58.6% females) were analyzed. The incidences of recurrent symptomatic VTE and major bleeding for up to 52 weeks after diagnosis were 3.2% and 2.2%, respectively. Multivariate analyses revealed chemotherapy and anemia as significant risk factors associated with recurrent symptomatic VTE and major bleeding, respectively. CONCLUSIONS: The efficacy and safety of DOACs in Japanese patients with VTE were determined in this real-world observational study.

Prophylactic Anticoagulation and Thrombosis in Hospitalized Patients with Clinically Stable COVID-19 at Admission: From the Practice-Based Observational Study.

Objectives: The potential benefit of routine prophylactic anticoagulation for all hospitalized patients with clinically stable coronavirus disease 2019 (COVID-19) is still controversial. Method: The CLOT-COVID Study was a multicenter observational study enrolling 2894 consecutive hospitalized patients with COVID-19. The current study population consisted of 1738 hospitalized patients with mild COVID-19 at admission not requiring oxygen administration, who were divided into 2 groups: patients with prophylactic anticoagulation (n = 326) and those without (n = 1412). Results: Patients with prophylactic anticoagulation had more severe status of the worst severity of COVID-19 during hospitalization compared with those without (mild: 38% versus 82%, moderate: 55% versus 17%, and severe or death at discharge: 6.4% versus 0.7%, P <0.001). During hospitalization, 8 patients (0.5%) developed thrombosis, and the incidences of thrombosis were numerically higher in patients with more severe status of worst severity of COVID-19 during hospitalization (mild: 0.2%, moderate: 1.2%, and severe or death at discharge: 3.2%). Conclusions: Among hospitalized patients with clinically stable COVID-19 at admission, patients who did not worsen in COVID-19 severity after admission rarely developed thrombosis, although patients with worsening of COVID-19 severity after admission more often received prophylactic anticoagulation and might have a higher risk of thrombosis.

Minimal Influence on Muscle Strength and Patient Reported Outcome Measures by Conjoined Tendon Detachment in Anterolateral Muscle-Sparing Total Hip Arthroplasty.

Purpose: The conjoined external rotator tendon (CERT), composed of the tendons of the gemellus superior, obturator internus (OI), and gemellus inferior muscles, stabilizes the hip joint. The study investigates the clinical and radiological effects of the CERT release during anterolateral-supine approach (ALSA) total hip arthroplasty (THA). Methods: A cohort of 60 patients who underwent ALSA THA was examined. Pre- and post-operative muscle width, muscle strength, and radiological data were compared between the CERT-detached and preserved groups. In addition, Clinical assessments were performed using the Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire and the short-form 36 questionnaires. Results: 58.3% had CERT detached, resulting in radiological atrophy of the OI muscle. Despite this, hip flexion, extension, and abduction muscle strength significantly improved at 6 months post-surgery. The detached CERT did not substantially affect patient-reported outcome measures, including pain and daily activities, within the 6-month follow-up. Discussion: The study suggests that while CERT detachment can lead to muscle atrophy, it has a limited impact on muscle strength and patient-reported outcome measures, indicating the muscle's potential redundancy. Preserving the CERT might enhance stability and prevent atrophy but could increase the risk of complications. CERT release is recommended when femur exposure is inadequate.

Efficacy and Safety of Warfarin for the Treatment of Venous Thromboembolism　- A Multicenter Prospective Observational Cohort Study in Japan (AKAFUJI Study).

BACKGROUND: A large-scale prospective study of the efficacy and safety of warfarin for the treatment of venous thromboembolism (VTE) has not been conducted in Japan. Therefore, we conducted a real-world prospective multicenter observational cohort study (AKAFUJI Study; UMIN000014132) to investigate the efficacy and safety of warfarin for VTE.Methods and Results: Between May 2014 and March 2017, 352 patients (mean [±SD] age 67.7±14.8 years; 57% female) with acute symptomatic/asymptomatic VTE were enrolled; 284 were treated with warfarin. The cumulative incidence of recurrent symptomatic VTE was higher in patients without warfarin than in those treated with warfarin (8.7 vs. 2.2 per 100 person-years, respectively; P=0.018). The cumulative incidence of bleeding complications was not significantly different between the 2 groups. The mean prothrombin time-international normalized ratio (PT-INR) during warfarin on-treatment was <1.5 in 180 patients, 1.5-2.5 in 97 patients, and >2.5 in 6 patients. The incidence of bleeding complications was significantly higher in patients with PT-INR >2.5, whereas the incidence of recurrent VTE was not significantly different between the 3 PT-INR groups. The cumulative incidence of recurrent VTE and bleeding complications did not differ significantly among those in whom VTE was provoked by a transient risk factor, was unprovoked, or was associated with cancer. CONCLUSIONS: Warfarin therapy with an appropriate PT-INR according to Japanese guidelines is effective without increasing bleeding complications, regardless of patient characteristics.

Prognostication of Patients with Pulmonary Thromboembolism with and without Residual Deep Vein Thrombosis: A Subanalysis of the J'xactly Study.

Objectives: It is unclear whether patients with acute pulmonary thromboembolism (PE) with and without residual deep vein thrombosis (DVT) have different prognoses, and there is debate over whether inferior vena cava filters (IVCFs) should be used in conjunction with oral anticoagulants in patients with venous thromboembolism (VTE). Materials and Methods: The J'xactly involved 1,016 patients and was a multicenter, prospective, observational research. In this subanalysis, 419 patients with PE with or without residual DVT who received rivaroxaban with or without IVCFs between February 2016 and April 2018 in Japan were examined. Results: Of 419 patients with PE, 320 had residual DVT. There was no difference between the groups with and without DVT in terms of the percentage of patients who experienced symptomatic PE recurrence (2.8% [9/320] vs. 3.0% [3/99]) or who died from VTE-related complications (0.9% [3/320] vs. 1.0% [1/99]). The percentages of patients with symptomatic PE recurrence were 0% and 3.2%, and the percentages of patients who died from VTE-related causes were 0% and 1.1%, respectively, in the groups with (n=39) and without (n=281) IVCF, albeit not being statistically different. Conclusion: Patients with PE with and without residual DVT did not have a different incidence of symptomatic PE recurrence. These results require additional study to be confirmed.

Rivaroxaban treatment for asymptomatic venous thromboembolism: insights from the J'xactly study.

BACKGROUND: An established treatment strategy for asymptomatic pulmonary embolism (PE) or deep vein thrombosis (DVT) remains uncertain in Japan; therefore, in this study, we clarify the characteristics and outcomes of symptomatic compared to asymptomatic patients with PE or DVT. METHODS: This prospective, multicenter sub-analysis of the J'xactly study in Japan included 1,016 patients (mean age, 68; 41% male) with venous thromboembolism (VTE) treated with rivaroxaban. RESULTS: Asymptomatic PE patients (47% of PE patients) were more likely to have active cancer and asymptomatic proximal DVT at lower severity than symptomatic PE patients, despite no differences in age, sex, or the proportion receiving intensive 30 mg/day-rivaroxaban. Patients with asymptomatic DVT (34% of DVT patients) were older, had higher rates of female sex, active cancer, and distal DVT, and received shorter, less intense rivaroxaban treatment. Incidences did not differ between asymptomatic and symptomatic PE patients for recurrent symptomatic VTE (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.22-1.62; P = 0.31) or major bleeding (HR, 0.68; 95% CI, 0.20-2.33; P = 0.58), nor between asymptomatic and symptomatic DVT patients for recurrent symptomatic VTE (HR, 0.56; 95% CI, 0.23-1.40; P = 0.21) and major bleeding (HR, 1.47; 95% CI, 0.54-3.97; P = 0.45). CONCLUSIONS: The real-world composite adverse event rate for treatment with rivaroxaban, as physician-adjusted for dose and duration, was similar for asymptomatic and symptomatic patients regardless of the presence of PE or DVT, suggesting a favorable safety profile for potential rivaroxaban treatment for asymptomatic VTE.

TiNbSn stems with gradient changes of Young's modulus and stiffness reduce stress shielding compared to the standard fit-and-fill stems.

BACKGROUND: The difference between Young's moduli of the femur and the stem causes stress shielding (SS). TiNbSn (TNS) stem has a low Young's modulus and strength with gradient functional properties during the change in elastic modulus with heat treatment. The aim of this study was to investigate the inhibitory effect of TNS stems on SS and their clinical outcomes compared to conventional stems. METHODS: This study was a clinical trial. Primary THA was performed using a TNS stem from April 2016 to September 2017 for patients in the TNS group. Unilateral THA was performed using a Ti6Al4V alloy stem from January 2007 to February 2011 for patients in the control group. The TNS and Ti6Al4V stems were matched in shape. Radiographs were obtained at the 1- and 3-year follow-ups. Two surgeons independently checked the SS grade and appearance of cortical hypertrophy (CH). The Japanese Orthopaedic Association (JOA) scores before and 1 year after surgery were assessed as clinical scores. RESULTS: None of the patients in the TNS group had grade 3 or 4 SS. In contrast, in the control group, 24% and 40% of patients had grade 3 and 4 SS at the 1- and 3-year follow-ups, respectively. The SS grade was lower in the TNS group than in the control group at the 1- and 3-year follow-ups (p < 0.001). The frequencies of CH in both groups were no significant difference at the 1- and 3-year follow-ups. The JOA scores of the TNS group significantly improved at 1 year after surgery and were comparable to control group. CONCLUSION: The TNS stem reduced SS at 1 and 3 years after THA compared to the proximal-engaging cementless stem, although the shapes of the stems matched. The TNS stem could reduce SS, stem loosening, and periprosthetic fractures. TRIAL REGISTRATION: Current Controlled Trials. ISRCTN21241251. https://www.isrctn.com/search?q=21241251 . The date of registration was October 26, 2021. Retrospectively registered.

Clinical Features Comparing Arterial Thrombosis and Venous Thromboembolism in Hospitalized Patients with COVID-19: Result from the CLOT-COVID Study.

Objectives: This study aimed to investigate the clinical features of arterial thrombosis and venous thromboembolism (VTE) in coronavirus disease 2019 (COVID-19). Methods: The CLOT-COVID Study was a retrospective, multicenter cohort study that enrolled 2,894 consecutively hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We compared the clinical features of arterial thrombosis and VTE. Results: Thrombosis was observed in 55 patients (1.9%) during hospitalization. Arterial thrombosis and VTE occurred in 12 (0.4%) and 36 (1.2%) patients, respectively. Among the 12 patients with arterial thrombosis, 9 (75%), 2 (17%), and 1 developed ischemic cerebral infarction, myocardial infarction, and acute limb ischemia, respectively, and there were five patients (42%) without comorbidities. Among 36 patients with VTE, 19 (53%) and 17 (47%) developed pulmonary embolism (PE) and deep vein thrombosis (DVT), respectively. PE was common in the early stages of hospitalization; whereas, DVT was common beyond the early stages of hospitalization. Conclusion: Among patients with COVID-19, arterial thrombosis was less common than VTE, although ischemic cerebral infarction seemed to be relatively common, and a certain number of patients developed arterial thrombosis even in the absence of known atherosclerosis risk factors.

Safety Profile and Effectiveness of Rivaroxaban for Patients With Venous Thromboembolism in Japan　- Results From Post-Marketing Surveillance (XASSENT).

BACKGROUND: The incidence of venous thromboembolism (VTE; pulmonary embolism [PE] and/or deep vein thrombosis [DVT]) in Japan is increasing, but relatively small numbers of patients from Japan have been included in studies investigating rivaroxaban (a direct factor Xa inhibitor) for the treatment of VTE and preventing its recurrence.Methods and Results: An open-label, prospective, observational study (XASSENT [NCT02558465]) investigated the safety profile and effectiveness of rivaroxaban for ≤2 years in the treatment of VTE and prevention of its recurrence in Japanese clinical practice. Primary outcomes were major bleeding and symptomatic recurrent VTE. Statistical analyses were exploratory and descriptive. Overall, 2,540 patients were enrolled (safety analysis population [SAP], n=2,387; effectiveness analysis population [EAP], n=2,386). In the SAP, >80% of patients received the approved rivaroxaban dose, the mean (standard deviation) age was 66.6 (15.0) years, ≈74% were >50 kg, and 43% had a creatinine clearance ≥80 mL/min. PE+DVT, PE only, and DVT only were reported in 42%, 8%, and 50% of patients, respectively, and active cancer in 17% of patients. Major bleeding was reported in 69 patients (2.89%; 3.60%/patient-year; SAP) and symptomatic PE/DVT recurrence in 26 patients (1.09%; 1.36%/patient-year; EAP) during the treatment period. CONCLUSIONS: XASSENT provided information on the expected proportions of bleeding and VTE recurrence during rivaroxaban treatment in Japanese clinical practice; no new concerns of safety or effectiveness were found.

Risk Factors and Impact on Outcomes of Thrombosis in Patients with COVID-19 in Japan: From the CLOT-COVID Study.

Objectives: The relationship between the thrombotic event and prognosis in patients with coronavirus disease 2019 (COVID-19) has not yet been fully investigated in Japan. Our study aimed to investigate the clinical outcomes and risk factors for thrombosis in hospitalized patients with COVID-19 in Japan. Materials and Methods: We compared the patient characteristics and clinical outcomes among patients with thrombosis (N=55) and those without thrombosis (N=2839) by using a large-scale data of CLOT-COVID study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800). Thrombosis included venous thromboembolism, ischemic stroke, myocardial infarction, and systemic arterial thromboembolism. Results: Higher rates of mortality and bleeding events were shown in hospitalized patients with COVID-19 with thrombosis compared to those without thrombosis (all-cause mortality, 23.6% vs. 5.1%, P<0.001; major bleeding, 23.6% vs. 1.6%, P<0.001). Multivariable analysis revealed that the independent risk factors of thrombosis were male sex, D-dimer level on admission>1.0 µg/mL, and moderate and severe COVID-19 status on admission. Conclusions: The development of thrombosis in hospitalized patients with COVID-19 was related to higher mortality and major bleeding, and several independent risk factors for thrombosis could help determine the patient-appropriate treatment for COVID-19.

Duration of Initial Intensive Rivaroxaban Therapy for Patients With Venous Thromboembolism　- Subanalysis of the J'xactly Study.

Background: Rivaroxaban, a direct oral anticoagulant, is used as a first-line treatment to prevent venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). However, whether 21 days is optimal for the initial treatment duration has not been investigated. Methods and Results: In this subanalysis of the prospective multicenter observational J'xactly study, which included 1,039 Japanese patients with acute symptomatic/asymptomatic DVT/PE who were prescribed rivaroxaban, the VTE recurrence rate and incidence of bleeding complications were assessed in 667 patients who underwent intensive rivaroxaban treatment (15 mg, twice daily) for a short (1-8 days), intermediate (9-16), or standard (17-24) duration. The short treatment duration group showed a tendency for increased VTE recurrence/aggravation compared with the standard treatment duration group (6.10% vs. 2.60% per patient-year). The intermediate treatment duration group showed a higher incidence of bleeding events than the standard treatment duration group (9.34% vs. 2.16% per patient-year), without major differences in patient characteristics between the groups. Conclusions: In this subanalysis of the real-world observational J'xactly study of VTE treatment and prevention in Japanese patients with acute symptomatic/asymptomatic DVT/PE, the standard initial intensive rivaroxaban treatment duration (17-24 days) appeared to be safe and effective, providing important insights into the clinical outcomes of the initial rivaroxaban treatment duration in this population.

Prognostic Impact of Prehospital Simple Risk Index in Patients With ST-Elevation Myocardial Infarction.

BACKGROUND: The simple risk index recorded in the emergency room (ER-SRI), which is calculated using the formula (heart rate × [age / 10]2) / systolic blood pressure, was shown to be able to stratify the prognosis in ST-elevation myocardial infarction (STEMI) patients. However, the prognostic impact of the prehospital simple risk index (Pre-SRI) remains unknown.Methods and Results: This study enrolled 2,047 STEMI patients from the Mie Acute Coronary Syndrome (ACS) registry. Pre-SRI was calculated using prehospital data and ER-SRI was calculated using emergency room data. The primary endpoint was 30-day all-cause mortality. The cut-off values of Pre-SRI and ER-SRI for predicting 30-day mortality were 34.8 and 34.1, with accuracies of 0.816 and 0.826 based on receiver operating characteristic analyses (P<0.001 for both). There was no difference in the accuracy of the 2 indices. Multivariate Cox regression analysis demonstrated that a High Pre-SRI (≥34) was a significant independent predictor of 30-day mortality. With combined Pre-SRI and ER-SRI assessment, patients with High Pre-SRI/High ER-SRI showed significantly higher mortality than those with High Pre-SRI/Low ER-SRI, Low Pre-SRI/High ER-SRI, and Low Pre-SRI/Low ER-SRI (P<0.001). The addition of High Pre-SRI to High ER-SRI showed incremental prognostic value of the Pre-SRI. CONCLUSIONS: Pre-SRI can identify high-risk STEMI patients at an early stage and combined assessment with Pre-SRI and ER-SRI could be of incremental prognostic value for risk stratification in STEMI patients.

Relationship between baseline D-dimer and prognosis in Japanese patients with venous thromboembolism: Insights from the J'xactly study.

Background: D-dimer is a biomarker of fibrin production and degradation, and changes in D-dimer concentration suggest fibrin clot formation, which is associated with thromboembolism and hypercoagulable states. Thus, an elevated D-dimer concentration could be a useful prognostic predictor for patients with venous thromboembolism (VTE). Methods and results: In this subanalysis of the J'xactly study, a prospective multicenter study conducted in Japan, we examined the clinical outcomes of 949 patients with VTE stratified by baseline D-dimer concentration. The median D-dimer concentration was 7.6 µg/ml (low D-dimer group: <7.6 µg/ml [n = 473, 49.8%]; high D-dimer group: ≥7.6 µg/ml [n = 476, 50.2%]). The mean age of the patients was 68 years, and 386 patients (40.7%) were male. Compared with the low D-dimer group, the high D-dimer group had more frequent pulmonary embolism with or without deep vein thrombosis (DVT), proximal DVT, atrial fibrillation, or diabetes mellitus, and underwent intensive treatment with 30 mg/day rivaroxaban. The incidence of composite clinically relevant events (recurrence or exacerbation of symptomatic VTE, acute coronary syndrome [ACS], ischemic stroke, death from any cause, or major bleeding) was higher in the high D-dimer group than in the low D-dimer group (11.1% vs. 7.5% per patient-year; hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; p = 0.025). There was no significant difference between the high and low D-dimer groups in the incidence of VTE (2.8% vs. 2.5% per patient-year, respectively; p = 0.788), ACS (0.4% per patient-year vs. not observed, respectively; p = 0.078), or major bleeding (4.0% vs. 2.1% per patient-year, respectively; p = 0.087), but there was a significant difference in the incidence of ischemic stroke (1.0% per patient-year vs. not observed, respectively; p = 0.004). Conclusion: Elevated D-dimer concentration may be an important prognostic predictor in Japanese patients with VTE.Clinical Trial Registration: UMIN CTR, UMIN000025072 (https://www.umin.ac.jp/ctr/index.htm).

Influence of obesity on incidence of thrombosis and disease severity in patients with COVID-19: From the CLOT-COVID study.

BACKGROUND: The influence of obesity on the development of thrombosis and severity of coronavirus disease 2019 (COVID-19) remains unclear. METHOD: The CLOT-COVID study was a retrospective multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 between April 2021 and September 2021 among 16 centers in Japan. The present study consisted of 2690 patients aged over 18 years with available body mass index (BMI), who were divided into an obesity group (BMI ≥30) (N = 457) and a non-obesity group (BMI <30) (N = 2233). RESULTS: The obesity group showed more severe status of COVID-19 at admission compared with the non-obesity group. The incidence of thrombosis was not significantly different between the groups (obesity group: 2.6 % versus non-obesity group: 1.9 %, p = 0.39), while the incidence of a composite outcome of all-cause death, or requirement of mechanical ventilation or extracorporeal membrane oxygenation during hospitalization was significantly higher in the obesity group (20.1 % versus 15.0 %, p < 0.01). After adjusting confounders in the multivariable logistic regression model, the risk of obesity relative to non-obesity for thrombosis was not significant (adjusted OR, 1.39; 95 % CI, 0.68-2.84, p = 0.37), while the adjusted risk of obesity relative to non-obesity for the composite outcome was significant (adjusted OR, 1.85; 95 % CI, 1.39-2.47, p < 0.001). CONCLUSIONS: In the present large-scale observational study, obesity was not significantly associated with the development of thrombosis during hospitalization; however, it was associated with severity of COVID-19.

Significant Impact of Age on Mortality and Non-significant Impact of Age on Thrombosis and Major Bleeding in Patients with COVID-19: From the CLOT-COVID Study.

AIM: There is scarce data on the impact of age on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into five groups according to age strata; -19, 20-39, 40-59, 60-79, and 80- years. RESULTS: Most patients under 19 had mild COVID-19 on admission (99%), while older patients had more severe COVID-19. The incidence rates of clinical outcomes during hospitalization in patients aged ≤ 19, 20-39, 40-59, 60-79, and 80 ≥ years were 0.0%, 0.5%, 2.2%, 2.7%, and 1.5% for thrombosis; 0.0%, 1.2%, 1.5%, 3.4%, and 2.0% for major bleeding; and 0.0%, 0.4%, 2.0%, 12.1%, and 16.8% for all-cause death, respectively. In the stratified analysis according to COVID-19 severity on admission, the incidences of thrombosis were generally higher among patients with more severe status, although those were not significantly different among age strata in all sub-types of COVID-19 severity. However, the incidences of all-cause death were significantly higher with increasing age in all sub-types of COVID-19 severity. CONCLUSIONS: In the current large observational study of patients with COVID-19, the risk of mortality became markedly higher with increased age. However, the risks of thrombosis and major bleeding did not necessarily increase as age increases, which seemed to be consistent irrespective of COVID-19 severity on admission.