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.

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.

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.

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.

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.

Association Between the Development of Thrombosis and Worsening of Disease Severity in Patients With Moderate COVID-19 on Admission　- From the CLOT-COVID Study.

BACKGROUND: The worsening of coronavirus disease 2019 (COVID-19) severity is a critical issue in current clinical settings and may be associated with the development of thrombosis.Methods and Results: This study used patient data obtained in the CLOT-COVID study, a retrospective multicenter cohort study. The demographics of patients with moderate COVID-19 on admission with and without worsened severity during hospitalization were compared and predictors were identified. Of 927 patients with moderate COVID-19 on admission, 182 (19.6%) had worsened severity during hospitalization. Patients with worsening of severity were older, more likely to have hypertension, diabetes, heart disease, and active cancer, and more likely to use pharmacological thromboprophylaxis. Patients with worsening of severity had higher D-dimer levels on admission and were more likely to develop thrombosis and major bleeding during hospitalization than those without worsening. Increased age (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03, P=0.005), diabetes (OR: 1.63, 95% CI: 1.11-2.33, P=0.012), D-dimer levels >1.0 µg/mL on admission (OR: 2.10, 95% CI: 1.45-3.03, P<0.001), and thrombosis (OR: 6.28, 95% CI: 2.72-14.53, P<0.001) were independently associated with worsening of COVID-19 severity. CONCLUSIONS: Approximately 20% of patients with moderate COVID-19 had worsened severity during hospitalization. Increased age, diabetes, D-dimer levels >1.0 µg/mL on admission, and the development of thrombosis during hospitalization were significantly associated with worsened COVID-19 severity.

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.

Mortality-associated Risk Factors in Hospitalized COVID-19 Patients in Japan: Findings of the CLOT-COVID Study.

BACKGROUND: Reports of mortality-associated risk factors in patients with the novel coronavirus disease 2019 (COVID-19) are limited. METHODS: We evaluated the clinical features that were associated with mortality among patients who died during hospitalization (n = 158) and those who were alive at discharge (n = 2,736) from the large-scale, multicenter, retrospective, observational cohort CLOT-COVID study, which enrolled consecutively hospitalized COVID-19 patients from 16 centers in Japan from April to September 2021. Data from 2,894 hospitalized COVID-19 participants of the CLOT-COVID study were analyzed in this study. RESULTS: Patients who died were older (71.1 years vs 51.6 years, P < 0.001), had higher median D-dimer values on admission (1.7 µg/mL vs 0.8 µg/mL, P < 0.001), and had more comorbidities. On admission, the patients who died had more severe COVID-19 than did those who survived (mild: 16% vs 63%, moderate: 47% vs 31%, and severe: 37% vs 6.2%, P < 0.001). In patients who died, the incidence of thrombosis and major bleeding during hospitalization was significantly higher than that in those who survived (thrombosis: 8.2% vs 1.5%, P < 0.001; major bleeding: 12.7% vs 1.4%, P < 0.001). Multivariable logistic regression analysis revealed that age >70 years, high D-dimer values on admission, heart disease, active cancer, higher COVID-19 severity on admission, and development of major bleeding during hospitalization were independently associated with a higher mortality risk. CONCLUSION: This large-scale observational study in Japan identified several independent risk factors for mortality in hospitalized patients with COVID-19 that could facilitate appropriate risk stratification of patients with COVID-19.

Therapeutic-Dose vs. Prophylactic-Dose Anticoagulation Therapy for Critically Ill Patients With COVID-19 in a Practice-Based Observational Study.

BACKGROUND: The potential benefit of therapeutic-dose anticoagulation for critically ill patients with coronavirus disease 2019 (COVID-19) is still controversial.Methods and Results: In the CLOT-COVID study, 225 patients with severe COVID-19 on admission requiring mechanical ventilation or extracorporeal membrane oxygenation were divided into patients with therapeutic-dose anticoagulation (N=110) and those with prophylactic-dose anticoagulation (N=115). There was no significant difference in the incidence of thrombosis between the groups (9.1% vs. 7.8%, P=0.73). CONCLUSIONS: Among a cohort of critically ill patients with COVID-19, approximately half received therapeutic-dose anticoagulation, although it did not show a potential benefit compared with prophylactic-dose anticoagulation.

Incidence, risk factors, and clinical impact of major bleeding in hospitalized patients with COVID-19: a sub-analysis of the CLOT-COVID Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) causes extensive coagulopathy and a potential benefit of anticoagulation therapy has been documented for prevention of thromboembolic events. Bleeding events has also been reported as a notable complication; whereas, the incidence, risks, and clinical impact of bleeding remain unclear. METHOD: The CLOT-COVID Study was a nationwide, retrospective, multicenter cohort study on consecutive hospitalized patients with COVID-19 in Japan between April 2021 and September 2021. In this sub-analysis, we compared the characteristics of patients with and without major bleeding; moreover, we examined the risk factors for and clinical impact of bleeding events. RESULTS: Among 2882 patients with COVID-19, 57 (2.0%) had major bleeding. The incidence of major bleeding increased with COVID-19 severity as follows: 0.5%, 2.3%, and 12.3% in patients with mild, moderate, and severe COVID-19, respectively. COVID-19 severity, history of major bleeding, and anticoagulant type/dose were independently and additively associated with the bleeding incidence. Compared with patients without major bleeding, those with major bleeding exhibited a longer duration of hospitalization (9 [6-14] vs 28 [19-43] days, P < 0.001) and higher mortality during hospitalization (4.9% vs. 35.1%, P < 0.001). CONCLUSIONS: In the real-world clinical practice, the incidence of major bleeding was not uncommon, especially in patients with severe COVID-19. Independent risk factors for major bleeding included history of major bleeding, COVID-19 severity, and anticoagulant use, which could be associated with poor clinical outcomes including higher mortality. Precise recognition of the risks for bleeding may be helpful for an optimal use of anticoagulants and for better outcomes in patients with COVID-19.

The intraoperative hip range of motion in total hip arthroplasty predicts postoperative patient's satisfaction for cutting toenails and putting on sock.

BACKGROUND: Restricted hip range of motion (ROM) has been proposed as a useful diagnostic tool for osteoarthritis. The relations between the intraoperative hip ROM under anesthesia in total hip arthroplasty (THA) and recovery of clinical mobility outcomes were unclear. This study evaluated the association between the intraoperative hip ROM under anesthesia in THA and the postoperative recovery of clinical mobility, including cutting toenails and putting on socks after THA. METHODS: The study was performed as a prospective cohort study and included 93 hips in 85 patients who underwent primary anterior-based muscle-sparing THA in the supine position. The hip ROM was evaluated under anesthesia before skin incision and intraoperative stability test. The Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ) was evaluated. A questionnaire on whether and how patients could cut toenails and putting on socks was assessed. The relationship between hip ROM at intraoperative stability tests and JHEQ moving score, cutting toenails, and putting on socks scores were evaluated statistically. RESULTS: We observed a week positive correlation between intraoperative hip ROM and the total of JHEQ mobility score. A moderate positive correlation was observed between external rotation angle with flexion 90°and cutting toenails and putting on socks score oh JHEQ. 94.6% and 96.8% of the patients could cut their toenails and putting on socks by themselves after surgery. The optimum cutoff range for high patient satisfaction for putting on socks and cutting toenails was 110° for flexion and 35°-40° for the external rotation angle in the intraoperative stability test. CONCLUSION: Hip ROM during intraoperative stability testing, especially the external rotation angle can predict postoperative outcomes and patient satisfaction for cutting toenails and putting on socks. We suggested that the capsule or capsular ligament release around the hip was increased to provide sufficient ROM without compromising stability.

Clinical Implication of the Right Ventricular/Left Ventricular Diameter Ratio in Patients with Pulmonary Thromboembolism.

The role of the right to left ventricular (RV/LV) diameter ratio in predicating long-term outcomes in patients with pulmonary thromboembolisms (PTEs) treated with direct oral anticoagulants is unclear.We investigated the association between the RV/LV diameter ratio and clinical outcomes in PTE patients under rivaroxaban from the data of a multicenter, prospective, observational study (J'xactly Study) in Japanese patients with acute venous thromboembolisms (VTEs) including deep vein thromboses, PTEs, or both. Of a total of 1,039 patients with an acute VTE (from December 2016 to April 2018), 429 were diagnosed with PTEs, however, the population in this study consists of 216 patients in whom the RV/LV diameter ratio measured on the axial CT or transthoracic echocardiogram was available.The RV/LV diameter ratio increased significantly with the severity of the PTE classification (nonmassive 0.79 [0.67-0.93], submassive 1.10 [0.83-1.31], massive 1.13 [0.94-1.19], arrest or collapse 1.38 [0.66-2.38], P < 0.001). During a median follow-up of 624 (550-690) days, a sum of the composite adverse events including recurrent VTEs, acute coronary syndrome, ischemic strokes, death from any cause, or major bleeding events occurred in 26 patients (12.0%, 7.58 events per 100 patient-years). Multivariate analysis revealed that an RV/LV diameter ratio ≥ 1.0 had no association with the incidence of composite adverse events (HR 1.34, 95% confidence interval 0.59-2.91, P = 0.48).In summary, in Japanese PTE patients under rivaroxaban, the RV/LV diameter ratio measured on the CT or transthoracic echocardiogram was associated with the PTE severity, but not with the clinical outcomes.

Association between Hip Center Position and Isokinetic Hip Muscle Performance after Anterolateral Muscle-Sparing Total Hip Arthroplasty.

Background and objectives: The superior placement of the acetabular cup induced the delayed recovery of abductor muscle moment after total hip arthroplasty (THA) with a conventional posterior approach. The anterior-based muscle-sparing (ABMS) THA effectively reduces soft tissue damage, including muscles. The influence of hip center position on anterior-based muscle-sparing (ABMS) total hip arthroplasty (THA) for post-operative hip muscle strength was unclear. We evaluate whether the hip center position affects the recovery of hip muscle strength after ABMS THA. Materials and Methods: The study was performed as a retrospective cohort study, and included 38 hips in 38 patients that underwent primary ABMS THA. Muscle strength was measured using isokinetic dynamometry before the operation, and at 6 and 12 months after surgery. The horizontal and vertical centers of rotation (H-COR and V-COR), vertical shift (V-shift), leg length, and global femoral offset were determined radiographically in reference to a previous report. Results: A weak negative correlation was observed between abduction muscle strength at 6 months and V-shift; a V-shift more than 15 mm demonstrated significantly decreased abductor muscle strength at 6 months. Conclusions: The superior placement of the hip center caused delayed recovery of abductor muscle strength in hips with anterolateral minimally invasive THA. There seems to exist no biomechanical reason why the same should not also be the case for the muscle-sparing approach.

Safety and Effectiveness of Apixaban in Japanese Patients With Venous Thromboembolism in Clinical Practice　- A Post-Marketing Surveillance.

BACKGROUND: A post-marketing surveillance study (STANDARD-VTE) evaluated the real-world safety and effectiveness of apixaban in Japanese patients prescribed for either the treatment of venous thromboembolism (VTE) or prevention of recurrent VTE.Methods and Results:Patients newly initiated on apixaban were followed up for 52 weeks or 28 days post-discontinuation. Subgroup analysis was performed on patients with and without active cancer, and on patients with provoked VTE and with unprovoked VTE. A total of 1,119 patients were enrolled. Of these, 43.1% were aged ≥75 years, 46.4% had body weight ≤60 kg, and 21.3% had active cancer; mean serum creatinine was 0.76 mg/dL. The incidence of adverse drug reactions (ADRs) was 8.85%, and that of severe ADRs was 3.22%. Incidence of any bleeding, major bleeding, and recurrent VTE was 6.70%, 3.40%, and 0.80%, respectively. In patients starting apixaban 10 mg twice daily, THE incidence of any bleeding and major bleeding was 7.72% and 3.86%, respectively. In patients with active cancer, THE incidence of any bleeding and major bleeding was 16.81% and 9.24%, respectively. CONCLUSIONS: No new safety signals of apixaban were identified in Japanese patients with VTE. In this study, the safety and effectiveness of apixaban in real-world practice was consistent with the results of the apixaban phase III trial.

Clinical Features of Venous Thromboembolism in Patients With Coronavirus Disease 2019 (COVID-19) in Japan　- A Case Series Study.

BACKGROUND: Suspicion that the coronavirus disease 2019 (COVID-19) caused venous thromboembolism (VTE).Methods and Results:We conducted a case series study of 5 VTE patients with COVID-19 in Japan. The median body mass index was 27.7 kg/m2, and all patients required mechanical ventilation during hospitalization. Patients were diagnosed as VTE in the intensive care unit (ICU), general ward, and outpatient ward. CONCLUSIONS: The current case series study revealed some clinical features of VTE patients with COVID-19 in Japan, including obese patients and those requiring mechanical ventilation during hospitalization, who should be followed closely for VTE, even after leaving the ICU.

Incidence and Clinical Features of Venous Thromboembolism in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) in Japan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) reportedly causes venous thromboembolism (VTE), but the status of this complication in Japan was unclear.Methods and Results:The VTE and COVID-19 in Japan Study is a retrospective, multicenter cohort study enrolling hospitalized patients with COVID-19 who were evaluated with contrast-enhanced computed tomography (CT) examination at 22 centers in Japan between March 2020 and October 2020. Among 1,236 patients with COVID-19, 45 (3.6%) were evaluated with contrast-enhanced CT examination. VTE events occurred in 10 patients (22.2%), and the incidence of VTE in mild, moderate, and severe COVID-19 was 0%, 11.8%, and 40.0%, respectively. COVID-19 patients with VTE showed a higher body weight (81.6 vs. 64.0 kg, P=0.005) and body mass index (26.9 vs. 23.2 kg/m2, P=0.04), and a higher proportion had a severe status for COVID-19 compared with those without. There was no significant difference in the proportion of patients alive at discharge between patients with and without VTE (80.0% vs. 88.6%, P=0.48). Among 8 pulmonary embolism (PE) patients, all were low-risk PE. CONCLUSIONS: Among a relatively small number of patients undergoing contrast-enhanced CT examination in Japanese real-world clinical practice, there were no VTE patients among those with mild COVID-19, but the incidence of VTE seemed to be relatively high among severe COVID-19 patients, although all PE events were low-risk without significant effect on mortality risk.

Mid-term results of a new femoral prosthesis using Ti-Nb-Sn alloy with low Young's modulus.

BACKGROUND: This study was performed to investigate the mid-term results of Ti-Nb-Sn (TNS) alloy stem with a low Young's modulus. METHODS: This study was a multicenter prospective cohort study. A total of 40 primary total hip arthroplasties performed between April 2016 and September 2017 was enrolled in this study. With the unique functional gradient properties by heating treatment, the strength of the proximal portion was enhanced, while the distal portion maintained a low Young's modulus. The surgeries were performed through the posterolateral approach using the TNS alloy stems. Radiographs were taken from immediately after surgeries until 3 years, and stress shielding and subsidence of the stems were evaluated. The incidences of the stem breakage were also assessed. Clinical assessments were performed using Japanese Orthopaedic Association (JOA) and Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) scores. RESULTS: Among the 40 enrolled patients, 36 patients were female and 4 were male. At 3 years after surgery, there were no radiologic signs of loosening, subsidence, or breakage of the stem. Stress shielding was observed in 26 hips (65%). Of 26 hips, 16 hips (40%) were grade 1 and 10 hips (25%) were grade 2. There was no advanced stress shielding. The JOA and JHEQ scores significantly improved compared with the preoperative scores. CONCLUSION: The current study using a new TNS alloy femoral stem showed good clinical outcomes at 3-year follow-up. Radiologically, there was no loosening or subsidence of the stem. The mild stress shielding was observed in 65% of patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21241251 . The date of registration was October 26, 2021. Retrospectively registered.

A Multicenter Prospective Observational Cohort Study to Investigate the Effectiveness and Safety of Rivaroxaban in Japanese Venous Thromboembolism Patients (The J'xactly Study).

BACKGROUND: There is insufficient real-world data on the current status of Japanese patients with venous thromboembolism (VTE) or its treatment and prevention with rivaroxaban.Methods and Results:In this multicenter, prospective, observational study conducted in Japan, 1,039 patients with acute symptomatic/asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) with or without DVT prescribed rivaroxaban were enrolled at 152 institutions and observed for a median of 21.3 months. Mean age was 68.0±14.7 years, mean body weight was 60.3±14.1 kg, 59.0% were females, and 19.0% had active cancer. Incidences of recurrence or aggravation of symptomatic VTE (primary effectiveness outcome) and major bleeding (principal safety outcome) were 2.6% and 2.9% per patient-year, respectively. These outcomes did not differ between patients with DVT and those with PE (primary effectiveness outcome: 2.6% vs. 2.5% per patient-year, P=0.810; principal safety outcome: 3.5% vs. 2.4% per patient-year, P=0.394). The incidence of composite clinically relevant events, including recurrence or aggravation of symptomatic VTE, acute coronary syndrome, ischemic stroke, all-cause death, or major bleeding events, was 9.2% per patient-year. Multivariate analysis revealed that male sex, being underweight, having active cancer, chronic heart and lung disease, and previous stroke were independent determinants for composite clinically relevant events. CONCLUSIONS: In Japanese clinical practice, a single-drug approach with rivaroxaban was demonstrated to be a valuable treatment for a broad range of VTE patients.

Selexipag for Chronic Thromboembolic Pulmonary Hypertension in Japanese Patients　- A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase II Study.

BACKGROUND: Selexipag is an oral prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. This study examined its efficacy and safety in Japanese patients with non-operated or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH).Methods and Results:This Phase II study was a randomized, double-blind, placebo-controlled parallel-group comparison. The primary endpoint was a change in pulmonary vascular resistance (PVR) from baseline to week 17. The main analysis involved a per-protocol set group of 28 subjects. The change in PVR (mean±SD) after 17 weeks of treatment in the selexipag group was -104±191 dyn·s/cm5, whereas that in the placebo group was 26±180 dyn·s/cm5. Thus, the treatment effect after 17 weeks of selexipag treatment was calculated as -130±189 dyn·s/cm5(P=0.1553). Although the primary endpoint was not met, for the group not concomitantly using a pulmonary vasodilator the PVR in the selexipag group was significantly decreased compared with placebo group (P=0.0364). The selexipag group also showed improvement in total pulmonary resistance and cardiac index. CONCLUSIONS: Selexipag treatment improved pulmonary hemodynamics in Japanese patients with CTEPH, but PVR did not show a significant difference between the selexipag and placebo groups. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111667]).

Acute Pulmonary Thromboembolism in a Patient with Nutcracker Syndrome and Antiphospholipid Syndrome.

Nutcracker syndrome (NCS), which is defined as compression of the left renal vein between the aorta and the superior mesenteric artery, is usually benign and self-limiting. Long-term renal venous retention increases the risk of renal vein thrombosis. However, NCS rarely develops into isolated thrombosis of the left renal vein; the reason for this process remains unknown. We describe a young man with antiphospholipid syndrome, who developed overt pulmonary thromboembolism due to an isolated thrombus in the left renal vein. Complicating antiphospholipid syndrome might trigger acute pulmonary thromboembolism (APTE) in patients with NCS. To the best of our knowledge, this is the first report of APTE arising due to isolated left renal vein thrombosis in patients with NCS.