Intratumoral Delivery of Paclitaxel in Solid Tumor from Biodegradable Hyaluronan Nanoparticle Formulations

In the current study, novel paclitaxel-loaded cross-linked hyaluronan nanoparticles were engineered for the local delivery of paclitaxel as a prototype drug for cancer therapy. The nanoparticles were prepared using a desolvation method with polymer cross-linking. In vitro cytotoxicity studies demonstrated that less than 75% of the MDA-MB-231 and ZR-75-1 breast cancer cells were viable after 2-day exposure to paclitaxel-loaded hyaluronan nanoparticles or free paclitaxel, regardless of the dose. These results suggest that hyaluronan nanoparticles maintain the pharmacological activity of paclitaxel and efficiently deliver it to the cells. Furthermore, in vivo administration of the drug-loaded nanoparticles via direct intratumoral injection to 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor in female rats was studied. The paclitaxel-loaded nanoparticles treated group showed effective inhibition of tumor growth in all treated rats. Interestingly, there was one case of complete remission of tumor nodule and two cases of persistent reduction of tumor size that was observed on subsequent days. In the case of free paclitaxel-treated group, the mean tumor volume increased almost linearly (R2 = 0.93) with time to a size that was 4.9-fold larger than the baseline volume at 57 days post-drug administration. Intratumoral administration of paclitaxel-loaded hyaluronan nanoparticles could be a promising treatment modality for solid mammary tumors

D-dimer levels and risk of recurrence following provoked venous thromboembolism: findings from the RIETE registry

BACKGROUND: Patients with venous thromboembolism (VTE) secondary to transient risk factors may develop VTE recurrences after discontinuing anticoagulation. Identifying at-risk patients could help to guide the duration of therapy. METHODS: We used the RIETE database to assess the prognostic value of d-dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. Transient risk factors were classified as major (postoperative) or minor (pregnancy, oestrogen use, immobilization or recent travel). RESULTS: In December 2018, 1655 VTE patients with transient risk factors (major 460, minor 1195) underwent d-dimer measurements after discontinuing anticoagulation. Amongst patients with major risk factors, the recurrence rate was 5.74 (95% CI: 3.19-9.57) events per 100 patient-years in those with raised d-dimer levels and 2.68 (95% CI: 1.45-4.56) in those with normal levels. Amongst patients with minor risk factors, the rates were 7.79 (95% CI: 5.71-10.4) and 3.34 (95% CI: 2.39-4.53), respectively. Patients with major risk factors and raised d-dimer levels (n = 171) had a nonsignificantly higher rate of recurrences (hazard ratio [HR]: 2.14; 95% CI: 0.96-4.79) than those with normal levels. Patients with minor risk factors and raised d-dimer levels (n = 382) had a higher rate of recurrences (HR: 2.34; 95% CI: 1.51-3.63) than those with normal levels. On multivariate analysis, raised d-dimers (HR: 1.74; 95% CI: 1.09-2.77) were associated with an increased risk for recurrences in patients with minor risk factors, not in those with major risk factors. CONCLUSIONS: Patients with raised d-dimer levels after discontinuing anticoagulant therapy for VTE provoked by a minor transient risk factor were at an increased risk for recurrences.status: publishe

D-dimer levels and risk of recurrence following provoked venous thromboembolism: findings from the RIETE registry

Background: Patients with venous thromboembolism (VTE) secondary to transient risk factors may develop VTE recurrences after discontinuing anticoagulation. Identifying at-risk patients could help to guide the duration of therapy. Methods: We used the RIETE database to assess the prognostic value of d-dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. Transient risk factors were classified as major (postoperative) or minor (pregnancy, oestrogen use, immobilization or recent travel). Results: In December 2018, 1655 VTE patients with transient risk factors (major 460, minor 1195) underwent d-dimer measurements after discontinuing anticoagulation. Amongst patients with major risk factors, the recurrence rate was 5.74 (95% CI: 3.19\u20139.57) events per 100 patient-years in those with raised d-dimer levels and 2.68 (95% CI: 1.45\u20134.56) in those with normal levels. Amongst patients with minor risk factors, the rates were 7.79 (95% CI: 5.71\u201310.4) and 3.34 (95% CI: 2.39\u20134.53), respectively. Patients with major risk factors and raised d-dimer levels (n = 171) had a nonsignificantly higher rate of recurrences (hazard ratio [HR]: 2.14; 95% CI: 0.96\u20134.79) than those with normal levels. Patients with minor risk factors and raised d-dimer levels (n = 382) had a higher rate of recurrences (HR: 2.34; 95% CI: 1.51\u20133.63) than those with normal levels. On multivariate analysis, raised d-dimers (HR: 1.74; 95% CI: 1.09\u20132.77) were associated with an increased risk for recurrences in patients with minor risk factors, not in those with major risk factors. Conclusions: Patients with raised d-dimer levels after discontinuing anticoagulant therapy for VTE provoked by a minor transient risk factor were at an increased risk for recurrences

Systolic blood pressure and mortality in acute symptomatic pulmonary embolism

BACKGROUND: The optimal cutoff for systolic blood pressure (SBP) level to define high-risk pulmonary embolism (PE) remains to be defined. METHODS: To evaluate the relationship between SBP levels on admission and mortality in patients with acute symptomatic PE, the current study included 39,257 consecutive patients with acute symptomatic PE from the RIETE registry between 2001 and 2018. Primary outcomes included all-cause and PE-specific 30-day mortality. Secondary outcomes included major bleeding and recurrent venous thromboembolism (VTE). RESULTS: There was a linear inverse relationship between admission SBP and 30-day all-cause and PE-related mortality that persisted after multivariable adjustment. Patients in the lower SBP strata had higher rates of all-cause death (reference: SBP 110-129 mmHg) (adjusted odds ratio [OR] 2.9; 95% confidence interval [CI], 2.0-4.2 for SBP 190 mmHg). Consistent findings were also observed for 30-day PE-related death. CONCLUSIONS: In patients with acute symptomatic PE, a low SBP portends an increased risk of all-cause and PE-related mortality. The highest mortality was observed in patients with SBP <70 mmHg.status: publishe