Factors influencing the prognosis of patients with acute cerebral infarction who received usual care: a multicenter prospective cohort study.

[Purpose] The prognostic factors for patients with acute stroke who received usual care (mobilization ≥48 h after admission) remain unclear. This study aimed to investigate the prognostic factors that predict functional outcomes using evaluations performed immediately after onset in patients with acute cerebral infarction who received usual care from admission until discharge. [Participants and Methods] Participants with acute cerebral infarction admitted to five acute care hospitals in Tokyo and Saitama, Japan and prescribed physical therapy were included. Participants information, functional evaluations, and progress were recorded during the first physical therapy session, mobilization, and discharge. Participants who received usual care were assigned to either the good- or poor-outcome group based on the Modified Rankin Scale at discharge. [Results] In total, 161 Participants receiving usual care (mobilization ≥48 h after admission) were included. Reinfarction and the First National Institutes of Health Stroke Scale score were identified as independent predictors of functional outcome at hospital discharge in participants who received usual care (median, 22.0 d). The cutoff NIHSS score was 4. [Conclusion] Our results provided evidence that the National Institutes of Health Stroke Scale score and reinfarction are useful predictors of functional outcomes in participants who received usual care.

Statins use and recurrent venous thromboembolism in the direct oral anticoagulant era: insight from the COMMAND VTE Registry-2.

Statins were reported to have a potential effect of primary prevention of venous thromboembolism (VTE), although that of secondary prevention remains uncertain. To investigate the association between statins use and recurrent VTE in the current era. The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive VTE patients among 31 centers in Japan between January 2015 and August 2020. We divided the entire cohort into 2 groups according to statins use at the time of discharge; the statins (N = 865) and no statins groups (N = 4332). The statins group was older (72.9 vs. 66.7 years, P < 0.001), and less often had active cancer (22.0% vs. 30.4%, P < 0.001). The cumulative incidence of discontinuation of anticoagulation was significantly lower in the statins group (60.3% vs. 52.6%, Log-rank P < 0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in the statins group (6.8% vs. 10.1%, Log-rank P = 0.01). Even after adjusting for the confounders, the lower risk of the statins group relative to the no statins group remained significant for recurrent VTE (HR 0.65, 95% CI 0.45-0.91, P = 0.01). The cumulative 5-year incidence of major bleeding was significantly lower in the statins group (12.2% vs. 14.1%, Log-rank P = 0.04), although, after adjusting for the confounders, the risk of the statins group relative to the no statins group turned to be insignificant (HR 0.77, 95% CI 0.59-1.00, P = 0.054). In this large real-world VTE registry, statins use was significantly associated with a lower risk for the recurrent VTE in the current era.

Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature.

Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

Direct oral anticoagulant-associated bleeding complications in patients with gastrointestinal cancer and venous thromboembolism.

BACKGROUND: Direct oral anticoagulants (DOACs) have become widely used for cancer-associated venous thromboembolism (VTE). However, DOAC-associated bleeding complications remain challenging, especially in patients with gastrointestinal (GI) cancer. This study aimed to compare the bleeding outcomes between patients with upper or lower GI cancers and those without GI cancer. METHODS: Using the COMMAND VTE Registry-2 database, which is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020, we identified 1149 active cancer patients with DOACs (upper GI cancer: N = 88; lower GI cancer: N = 114; non-GI cancer: N = 947). The primary outcome was major bleeding during anticoagulation therapy, which was evaluated in the competing risk regression model. RESULTS: The upper GI cancer group had a lower mean body weight, and most often had anemia. The cumulative 5-year incidence of major bleeding was higher in the upper GI cancer group (upper GI cancer: 22.4 %, lower GI cancer: 15.4 %, and non-GI cancer: 11.6 %, P = 0.015). The most frequent major bleeding site in the upper GI cancer group was the upper GI (53 %), followed by the lower GI (24 %). After adjusting for the confounders, the excess risk in upper GI cancer relative to non-GI cancer remained significant for major bleeding (adjusted subhazard ratio, 2.25; 95 %CI, 1.31-3.87, P = 0.003), but that in lower GI cancer was insignificant. CONCLUSIONS: Upper GI cancer, but not lower GI cancer, as compared to non-GI cancer was associated with a higher risk for major bleeding during anticoagulation therapy with DOACs. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000044816.

Comparison of bioactive substances in novel-developed freeze-dried platelet-rich plasma (PRP) and activated normal PRP, and investigation of bioactive substance levels after long-term storage.

Introduction: In recent years, biotherapy in orthopedics has become widespread, and platelet-rich plasma (PRP) has been readily used to treat sports injuries and osteoarthritis. Production of freeze-dried PRP (PRP-FD) results in PRP that is in powder form, allowing it to be stored for long periods at room temperature. Using this technology, we have developed Valuable Platelet-Derived Factor Concentrate Freeze Dry (VFD). However, whether VFD contains sufficient levels of bioactive substances (BS) remains unknown and retains the same levels of BS during long-term storage. In this study, we examined whether VFD contains sufficient amounts of BS and whether they retain these BS levels during long-term storage. Methods: Peripheral blood was collected from 10 healthy men (mean ± SD: 46.5 ± 15 years old) and various BS, including transforming growth factor ß (TGF-ß), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), tissue inhibitors of metalloproteinases-1 (TIMP-1), interleukin-1 receptor antagonist (IL-1ra), matrix metallopeptidase-9 (MMP-9), and interleukin-6 (IL-6), were compared between VFD and normal PRP samples, including both leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP). VFD was prepared using two rounds of centrifugation. LP-PRP and LR-PRP were activated by freezing and thawing before measurement. To evaluate the effects of long-term storage, the BS of VFD purified from five professional football players was compared between baseline and 1 year after storage. Results: In terms of the growth factors, the TGF-ß and EGF levels were higher in LR-PRP than in VFD and LP-PRP (p < 0.05), while the bFGF levels were higher in VFD than in the LR-PRP and LP-PRP groups (p < 0.01). In terms of anti-inflammatory cytokines, the TIMP-1 level was lower in VFD than that in the other groups (p < 0.01), whereas the IL-1ra levels were higher in VFD than those in LP-PRP (p < 0.05) and lower than those in LR-PRP (p < 0.01). In terms of inflammatory enzymes and cytokines, the IL-1ra level was higher in VFD than that in LP-PRP (p < 0.05) and lower than that in LR-PRP (p < 0.01), whereas the IL-6 levels did not differ among the groups. Furthermore, the TGF-ß, bFGF, TIMP-1, and IL-1ra levels were 5.61 â†’ 3.38 (x103 pg/µL), 61.0 â†’ 63.0 (pg/µL), 3.4 â†’ 2.7 (x105 pg/µL), and 14.9 â†’ 14.5 (x103 pg/µL) at baseline and 1 year later, respectively. No significant differences in the BS levels were observed between baseline and 1 year after storage. Conclusions: The VFD samples prepared in this study exhibited higher levels of anti-inflammatory cytokines than LP-PRP and contained growth factor levels similar to LP-PRP and LR-PRP. In addition, the BS levels in VFD samples were maintained after one year of storage. These results suggest that VFD can be prepared and stored and may serve as a novel treatment strategy for sports injuries in high-risk groups, such as athletes.

Edoxaban, Rivaroxaban, or Apixaban for Cancer-Associated Venous Thromboembolism in the Real World: Insights from the COMMAND VTE Registry-2.

BACKGROUND: Real-world data on clinical characteristics and outcomes related to the use of different direct oral anticoagulants (DOACs) for cancer-associated venous thromboembolism (VTE) is lacking. METHODS: The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive patients with acute symptomatic VTE from 31 centers in Japan from January 2015 to August 2020. Our study population comprised 1,197 patients with active cancer who were divided into the edoxaban (N = 643, 54%), rivaroxaban (N = 297, 25%), and apixaban (N = 257, 22%) groups. RESULTS: The cumulative 5-year incidence of recurrent VTE (9.3, 10.2, and 8.5%, respectively, p = 0.82) and all-cause death (67.5, 66.8, and 63.8%, respectively, p = 0.22) did not differ among the groups. Despite adjusting for confounders, the risks of recurrent VTE and all-cause death did not differ significantly among the groups. The cumulative 5-year incidence of major and clinically relevant bleeding was significantly lower in the rivaroxaban group than those in the other groups (22.6, 14.0, and 22.8%, p = 0.04; and 37.6, 26.8, and 38.3%, p = 0.01, respectively). After adjusting for confounders, in the rivaroxaban group, the risk for major bleeding was numerically lower (hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.40-1.01) and that of clinically relevant all bleeding was significantly lower (HR: 0.67, 95% CI: 0.48-0.92) than those in the edoxaban group. CONCLUSION: The risks of recurrent VTE and all-cause death did not differ significantly among the different DOACs ; however, the risk of bleeding events could differ, with a potentially lower risk of bleeding with rivaroxaban.

Subclass phenotypes in patients with unprovoked venous thromboembolisms using a latent class analysis.

BACKGROUND: Patients with unprovoked venous thromboembolisms (VTEs) can be sub-classified based on the different phenotypes using a latent class analysis (LCA), which might be useful for selecting individual management strategies. METHODS: In the COMMAND VTE Registry-2 database enrolling 5197 VTE patients, the current derivation cohort consisted of 1556 patients with unprovoked VTEs. We conducted clustering with an LCA, and the patients were classified into subgroups with the highest probability. We compared the clinical characteristics and outcomes among the developed subgroups. RESULTS: This LCA model proposed 3 subgroups based on 8 clinically relevant variables, and classified 592, 813, and 151 patients as Class I, II, and III, respectively. Based on the clinical features, we named Class I the younger, Class II the older with a few comorbidities, and Class III the older with many comorbidities. The cumulative 3-year anticoagulation discontinuation rate was highest in the older with many comorbidities (Class III) (39.9 %, 36.1 %, and 48.4 %, P = 0.02). There was no significant difference in the cumulative 5-year incidence of recurrent VTEs among the 3 classes (12.8 %, 11.1 %, and 4.0 % P = 0.20), whereas the cumulative 5-year incidence of major bleeding was significantly higher in the older with many comorbidities (Class III) (7.8 %, 12.7 %, and 17.8 %, P = 0.04). CONCLUSION: The current LCA revealed that patients with unprovoked VTEs could be sub-classified into further phenotypes depending on the patient characteristics. Each subclass phenotype could have different clinical outcomes risks especially a bleeding risk, which could have a potential benefit when considering the individual anticoagulation strategies. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm COMMAND VTE Registry-2: Unique identifier, UMIN000044816 COMMAND VTE Registry: Unique identifier, UMIN000021132.

Fragility and long-term clinical outcomes in patients with venous thromboembolism receiving direct oral anticoagulants: From the COMMAND VTE REGISTRY-2.

INTRODUCTION: There is limited data on the safety of direct oral anticoagulants (DOACs) in fragile patients with venous thromboembolism (VTE). MATERIALS AND METHODS: We used the COMMAND VTE Registry-2 enrolling patients with acute symptomatic VTE. The study population consisted of 3928 patients receiving DOACs, who were divided into fragile (2136 patients) and non-fragile groups (1792 patients). Fragility was defined as patients of age ≥ 75 years, creatinine clearance level ≤ 50 ml/min, and/or body weight ≤ 50 kg. RESULTS: The fragile group significantly more often received reduced doses of DOACs compared to the non-fragile group (51 % and 19 %, P < 0.001). The cumulative 5-year incidence of major bleeding was numerically higher in the fragile group than the non-fragile group (15.0 % and 11.1 %, P = 0.052), even with no significant excess risk after adjusting for confounders (HR 1.03, 95%CI 0.81-1.31, P = 0.78). The cumulative 5-year incidence of clinically relevant bleeding was significantly higher in the fragile group than the non-fragile group (28.6 % and 19.6 %, P < 0.001), even after adjusting for confounders (HR 1.28, 95%CI 1.08-1.53, P = 0.005). There was no significant difference in cumulative 5-year incidence of recurrent VTE between the groups (9.6 % and 8.9 %, P = 0.68), which was consistent after adjusting for confounders (HR 1.13, 95%CI 0.84-1.51, P = 0.41). CONCLUSIONS: Among VTE patients receiving DOACs, fragile patients were associated with a numerically higher rate of major bleeding and a significantly increased risk of clinically relevant bleeding, but not an increased risk of recurrent VTE.

Sub-10-fs pulse generation from 10 nJ Yb-fiber laser with cascaded nonlinear pulse compression.

We demonstrate cascaded nonlinear pulse compression of a Yb-doped fiber laser. The system is based on two pulse compression stages with bare single-mode fiber (SMF) and ultra-high NA (UHNA) fibers combined with two pairs of chirped mirrors. The 10 nJ, 110 fs input pulses are compressed down to 9.1 fs at 90 MHz, revealing a broadband spectrum from 800 nm to 1350 nm. This technique provides a simple approach to sub-10-fs compact Yb-doped fiber lasers for a variety of applications.

Transition of management strategies and long-term outcomes in cancer-associated venous thromboembolism from the warfarin era to the direct oral anticoagulant era.

BACKGROUND: There have been still limited data on the transition of management strategies and clinical outcomes after introduction of direct oral anticoagulant (DOAC) for cancer-associated venous thromboembolism (VTE) in the real-world clinical practice. METHODS: Using the 2 series of multicenter COMMAND VTE registries in Japan enrolling consecutive patients with acute symptomatic VTE, we compared 695 patients with cancer-associated VTE in the Registry-1 of the warfarin era and 1507 patients in the Registry-2 of the DOAC era. RESULTS: Regarding oral anticoagulation therapy, 576 patients (82.9 %) in the Registry-1 received warfarin, whereas 1119 patients (79.6 %) in the Registry-2 received DOACs. The cumulative 3-year incidence of discontinuation of anticoagulation was not significantly different between the 2 registries (56.7 % vs. 62.7 %, P = 0.11). The cumulative 5-year incidence of recurrent VTE was significantly lower in the Registry-2 than in the Registry-1 (17.7 % vs. 10.1 %, P < 0.001). The cumulative 5-year incidence of major bleeding was significantly lower in the Registry-2 than in the Registry-1 (26.6 % vs. 20.4 %, P = 0.045). The proportion of gastrointestinal bleeding numerically increased from the Registry-1 to the Registry-2 (46.7 % and 49.5 %), whereas that of intracranial bleeding numerically decreased from the Registry-1 to the Registry-2 (17.1 % and 14.1 %). CONCLUSIONS: In the current historical comparison of cancer-associated VTE between the 2 large real-world registries, there was a striking change in the treatment strategies with decreased risks of recurrent VTE and major bleeding in the DOAC era compared with those in the warfarin era, while there seemed to be unmet needs of DOAC-related gastrointestinal bleeding. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm UNIQUE IDENTIFIER: UMIN000044816.

Cancer-associated venous thromboembolism in the direct oral anticoagulants era: Insight from the COMMAND VTE Registry-2.

BACKGROUND: There is a paucity of data on real-world management strategies and clinical outcomes of cancer-associated venous thromboembolism (VTE) in the direct oral anticoagulants (DOACs) era. OBJECTIVES: To investigate the status of cancer-associated VTE in the DOAC era. METHODS: This multicenter, retrospective cohort study among 31 centers in Japan between 2015 and 2020 enrolled 5197 consecutive patients with acute symptomatic VTE, who were divided into 1507 patients (29 %) with active cancer and 3690 patients (71 %) without. RESULTS: The cumulative 3-year rate of anticoagulation discontinuation was significantly higher in patients with active cancer than in those without (62.7 % vs. 59.1 %, P < 0.001). The cumulative 5-year incidence of recurrent VTE was higher in patients with active cancer than in those without (10.1 % vs. 9.1 %, P = 0.01), however, after adjusting for the confounders and competing risk of mortality, the excess risk of the active cancer group relative to the no active cancer group was no longer significant (HR: 0.95, 95 % CI: 0.73-1.24). The cumulative 5-year incidence of major bleeding was much higher in the active cancer group (20.4 % vs. 11.6 %, P < 0.001). Even after adjusting for the confounders and competing risk of mortality, the risk of the active cancer group relative to the no active cancer group remained significant (HR: 1.36, 95 % CI: 1.11-1.66). CONCLUSIONS: The current large real-world registry revealed that the risk of major bleeding was still higher in patients with active cancer than in those without, leading to the frequent anticoagulation discontinuation, which has been still a huge challenge to overcome in the DOAC era.

Anomalous Hall Transport by Optically Injected Isospin Degree of Freedom in Dirac Semimetal Thin Film.

Chirality of massless fermions emerging in condensed matter is a key to understand their characteristic behavior as well as to exploit their functionality. However, the chiral nature of massless fermions in Dirac semimetals has remained elusive, due to equivalent occupation of carriers with the opposite chirality in thermal equilibrium. Here, we show that the isospin degree of freedom, which labels the chirality of massless carriers from a crystallographic point of view, can be injected by circularly polarized light. Terahertz Faraday rotation spectroscopy successfully detects the anomalous Hall conductivity by a light-induced isospin polarization in a three-dimensional Dirac semimetal, Cd3As2. Spectral analysis of the Hall conductivity reveals a long scattering time and a long decay time, which are characteristic of the isospin. The long-lived, robust, and reversible character of the isospin promises a potential application of Dirac semimetals in future information technology.

Probing thermal dissipation dimensionality to laser ablation in the pulse duration range from 300 fs to 1 µs.

We propose a quantitative method to determine the thermal dissipation dimensionality to laser ablation. We derived an analytical expression for the melting condition due to a single pulse for arbitrary spot diameters and pulse durations, which explicitly contains the dimensionality of the thermal diffusion process. As a demonstration, we compared the analytical expression with multi-shot ablation thresholds measured over pulse durations of more than six orders of magnitude for copper. The result shows that the thermal dissipation processes dominate for pulse durations longer than 5 ps, while nonthermal processes begin to dominate for shorter pulse durations.

Association Between the Liver Fibrosis Markers and Scores, and Hemodynamic Congestion Assessed by Peripheral Venous Pressure in Patients With Acute Heart Failure.

Background Peripheral venous pressure (PVP) has been shown to be a reliable surrogate for right atrial pressure in assessing congestion in patients with heart failure (HF). Liver fibrosis markers and scores can be useful in assessing organ injury in patients with acute HF. This study aimed to investigate the association of liver fibrosis markers and scores with PVP in patients with acute HF. Methods and Results The 7S domain of the collagen type IV N-terminal propeptide (P4NP 7S), aspartate aminotransferase-to-platelet ratio index, fibrosis-4, and nonalcoholic fatty liver disease fibrosis score were determined along with PVP measurements before discharge in 229 patients with acute HF. The strongest correlation with PVP was found for P4NP 7S (Pearson r=0.40). Patients with high P4NP 7S levels (≥median [6.2 ng/mL]) had an increased risk of cardiovascular death or HF hospitalization (adjusted hazard ratio [HR], 1.80 [95% CI, 1.09-3.04], P=0.02). The concomitant high PVP (≥mean [8 mm Hg])/high P4NP 7S group, in contrast to the high PVP/low P4NP 7S or low PVP/high P4NP 7S group, had a significant risk relative to the low PVP/low P4NP 7S group for cardiovascular death or HF hospitalization (adjusted HR, 2.63 [95% CI, 1.43-5.05], P=0.002). A sustained elevation in PVP for 1 month postdischarge was associated with a persistent increase in P4NP 7S. Conclusions The study demonstrated the relationship between the liver fibrosis marker P4NP 7S and congestion. PVP and P4NP 7S could be useful for assessing congestion-related organ injury and predicting prognosis in patients with acute HF.

Application of the RIETE score to identify low-risk patients with pulmonary embolism: From the COMMAND VTE Registry.

BACKGROUND: The RIETE score could be specifically useful for identification of low-risk pulmonary embolism (PE) patients for home treatment. However, the external validation of the RIETE score has been limited. METHODS: The COMMAND VTE Registry is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). The current study population consisted of 1479 patients with acute PE, who were divided into 2 groups; RIETE scores of 0 (N = 260) and ≥ 1 (N = 1219). RESULTS: The cumulative 10-day and 30-day incidences of a composite endpoint of all-cause death, recurrent PE, or major bleeding were lower in patients with the RIETE score of 0 than in those with the RIETE score of ≥1 (10-day: 0.4 % vs. 6.7 %, P < 0.001, and 30-day: 0.4 % vs. 10.0 %, P < 0.001). The area under the receiver-operating characteristic curve (AUC) in the RIETE score for the 10-day composite endpoint showed numerically better predictive ability than that in the sPESI score (0.77 vs. 0.73, P = 0.07), and the AUC in the RIETE score for the 30-day composite endpoint showed significantly better predictive ability than that in the sPESI score (0.77 vs. 0.71, P = 0.003). CONCLUSIONS: The RIETE score was well validated in the current large real-world registry. The RIETE score of 0 could identify patients with reasonably low risks of the 10-day and 30-day composite endpoint of all-cause death, recurrent PE, or major bleeding.

Disentangling the Competing Mechanisms of Light-Induced Anomalous Hall Conductivity in Three-Dimensional Dirac Semimetal.

We experimentally elucidate the origin of the anomalous Hall conductivity in a three-dimensional Dirac semimetal, Cd_{3}As_{2}, driven by circularly polarized light. Using time-resolved terahertz Faraday rotation spectroscopy, we determine the transient Hall conductivity spectrum with special attention to its sign. Our results clearly show the dominance of direct photocurrent generation assisted by the terahertz electric field. The contribution from the Floquet-Weyl nodes is found to be minor when the driving light is in resonance with interband transitions. We develop a generally applicable classification of microscopic mechanisms of light-induced anomalous Hall conductivity.

Anticoagulation strategies and long-term recurrence in patients with venous thromboembolism in the era of direct oral anticoagulants.

BACKGROUND: There has been limited data on anticoagulation strategies and long-term recurrence in patients with venous thromboembolism (VTE) in the era of direct oral anticoagulant (DOAC). METHODS: The COMMAND VTE Registry-2 is a multicenter retrospective cohort study enrolling 5197 consecutive patients with acute symptomatic VTE between January 2015 and August 2020 among 31 centers in Japan. In this primary report, the entire cohort was divided into 5 groups; major transient risk factors (N = 475, 9.1%), minor transient risk factors (N = 788, 15%), unprovoked (N = 1913, 37%), non-malignant persistent risk factors (N = 514, 9.9%), and active cancer (N = 1507, 29%) groups. RESULTS: DOACs were administered in 79% of patients who received oral anticoagulants. Discontinuation of anticoagulant at 1 year was most frequent in the major transient risk factors group (57.2%, 46.3%, 29.1%, 32.0%, and 45.6%). The cumulative 5-year incidence of recurrent VTE was lowest in the major transient risk factors group (2.6%, 6.4%, 11.0%, 12.1%, and 10.1%, P < 0.001). The cumulative 5-year incidence of major bleeding was highest in the active cancer group (9.8%, 11.4%, 11.0%, 15.5%, and 20.4%, P < 0.001). After discontinuation of anticoagulation therapy, the cumulative 5-year incidence of recurrent VTE was highest in the unprovoked group (3.3%, 11.0%, 24.9%, 17.5%, and 11.8%, P < 0.001). CONCLUSIONS: In this large real-world VTE registry, anticoagulation strategies and long-term recurrence widely differed depending on the baseline characteristics. Detailed risk stratifications of recurrent VTE could be useful for decision-making of anticoagulation strategies, whereas the bleeding-risk assessment might be especially important in the era of DOAC. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000044816.

Application of first-generation high- and low-dose drug-coated balloons to the femoropopliteal artery disease: a sub-analysis of the POPCORN registry.

BACKGROUND: Drug-coated balloons (DCBs) have significantly changed endovascular therapy (EVT) for femoropopliteal artery (FPA) disease, in terms of the expansion of indications for EVT for symptomatic lower extremity arterial disease (LEAD). However, whether there is a difference in the performance among individual DCBs has not yet been fully discussed. The present sub-analysis of real-world data from a prospective trial of first-generation DCBs compared the clinical outcomes between high- and low-dose DCBs using propensity score matching methods. The primary endpoint was the restenosis-free and revascularization-free rates at 1 year. RESULTS: We compared 592 pairs matched for patient and lesion characteristics using propensity score matching among a total of 2,507 cases with first-generation DCBs (592 and 1,808 cases in the Lutonix low-dose and In.PACT Admiral high-dose DCB groups, respectively). There were no differences in patient/lesion characteristics, procedural success rates, or complications between the two groups. First-generation low-dose DCB had significantly lower patency (73.3% [95% confidence interval, 69.6%-77.3%] in the low-dose DCB group versus 86.2% [84.1%-88.3%] in the high-dose DCB group; P < 0.001) and revascularization-free (84.9% [81.9%-88.1%] versus 92.5% [90.8%-94.1%]; P < 0.001) rates. Chronic kidney disease on dialysis, cilostazol use, anticoagulant use, and severe calcification had a significant interaction effect in the association (all P < 0.05). CONCLUSIONS: EVT to FPA with first-generation DCBs had inferior low-dose patency outcomes as compared with high-dose outcomes in the present cohort. LEVEL OF EVIDENCE: Sub analysis of a prospective multicenter study.

Jitter correction for asynchronous optical sampling terahertz spectroscopy using free-running pulsed lasers.

We demonstrate a jitter correction method for asynchronous optical sampling (ASOPS) terahertz (THz) time-domain spectroscopy using two free-running oscillators. This method simultaneously records the THz waveform and a harmonic of the laser repetition rate difference, Δ f r, to monitor the jitter information for software jitter correction. By suppressing the residual jitter below 0.1 ps, the accumulation of the THz waveform is achieved without losing the measurement bandwidth. Our measurement of water vapor successfully resolves the absorption linewidths below 1 GHz, demonstrating a robust ASOPS with a flexible, simple, and compact setup without any feedback control or additional continuous-wave THz source.