In pursuit of giants: I. The evolution of the dust-to-stellar mass ratio in distant dusty galaxies

The dust-to-stellar mass ratio (Mdust/M?) is a crucial, albeit poorly constrained, parameter for improving our understanding of the complex physical processes involved in the production of dust, metals, and stars in galaxy evolution. In this work, we explore trends of Mdust/M? with dierent physical parameters and using observations of 300 massive dusty star-forming galaxies detected with ALMA up to z 5. Additionally, we interpret our findings with dierent models of dusty galaxy formation. We find that Mdust/M? evolves with redshift, stellar mass, specific star formation rates, and integrated dust size, but that evolution is dierent for mainsequence galaxies than it is for starburst galaxies. In both galaxy populations, Mdust/M? increases until z 2, followed by a roughly flat trend towards higher redshifts, suggesting ecient dust growth in the distant universe. We confirm that the inverse relation between Mdust/M? and M? holds up to z 5 and can be interpreted as an evolutionary transition from early to late starburst phases. We demonstrate that the Mdust/M? in starbursts reflects the increase in molecular gas fraction with redshift and attains the highest values for sources with the most compact dusty star formation. State-of-the-art cosmological simulations that include self-consistent dust growth have the capacity to broadly reproduce the evolution of Mdust/M? in main-sequence galaxies, but underestimating it in starbursts. The latter is found to be linked to lower gas-phase metallicities and longer dust-growth timescales relative to observations. The results of phenomenological models based on the main-sequence and starburst dichotomy as well as analytical models that include recipes for rapid metal enrichment are consistent with our observations. Therefore, our results strongly suggest that high Mdust/M? is due to rapid dust grain growth in the metal-enriched interstellar medium. This work highlights the multi-fold benefits of using Mdust/M? as a diagnostic tool for: (1) disentangling main-sequence and starburst galaxies up to z 5; (2) probing the evolutionary phase of massive objects; and (3) refining the treatment of the dust life cycle in simulations

Outcomes during anticoagulation in patients with symptomatic vs. incidental splanchnic vein thrombosis

Introduction: Current guidelines recommend the use of anticoagulant therapy in patients with symptomatic splanchnic vein thrombosis (SVT) and suggest no routine anticoagulation in those with incidental SVT. Methods: We used the RIETE (Registro Informatizado Enfermedad Trombo Emb\uf3lica) registry to assess the rate and severity of symptomatic venous thromboembolism (VTE) recurrences and major bleeding events appearing during the course of anticoagulation in patients with symptomatic or incidental SVT. Results: In March 2017, 521 patients with SVT were recruited. Of them, 212 (41%) presented with symptomatic SVT and 309 had incidental SVT. Most (93%) patients received anticoagulant therapy (median, 147 days). During the course of anticoagulation, 20 patients developed symptomatic VTE recurrences (none died) and 26 had major bleeding (fatal bleeding, 5). On multivariable analysis, patients with incidental SVT had a non-significantly higher risk for symptomatic VTE recurrences (adjusted hazard ratio [HR]: 2.04; 95%CI: 0.71\u20135.88) and a similar risk for major bleeding (HR: 1.12; 95%CI: 0.47\u20132.63) than those with symptomatic SVT. Active cancer was associated with at increased risk for VTE recurrences (HR: 3.06; 95%CI: 1.14\u20138.17) and anaemia (HR: 4.11; 95%CI: 1.45\u201311.6) or abnormal prothrombin time (HR: 4.10; 95%CI: 1.68\u201310.1) were associated with at increased risk for major bleeding. Conclusions: The rates of recurrent SVT and major bleeding were similar between patients with incidental or symptomatic SVT. Because the severity of bleeding complications during anticoagulation may outweigh the severity of VTE recurrences in both groups, further studies should identify those SVT patients who benefit from anticoagulant therapy

Silent pulmonary embolism in patients with proximal deep vein thrombosis in the lower limbs

BACKGROUND: One in every three patients with deep vein thrombosis (DVT) in the lower limbs may have silent pulmonary embolism (PE), but its clinical relevance has not been thoroughly studied. METHODS: We used the RIETE Registry data to study patients with proximal DVT and no PE symptoms, but with a systematic search for PE. We compared the outcome of DVT patients with silent PE and those with no PE. RESULTS: Of 2375 patients with DVT, 842 (35%) had silent PE and 1533 had no PE. During the first 15 days of anticoagulation, patients presenting with silent PE had a higher incidence of symptomatic PE events than those with no PE (0.95% vs. 0.13%; P = 0.015), with a similar incidence of major bleeding (0.95% vs. 1.63%; P = 0.09). In patients with silent PE, the incidence of PE events during the first 15 days was equal to the incidence of major bleeding (eight events each), but in those with no PE the incidence of PE events was eight times lower (3 vs. 25 bleeding events). Multivariate analysis confirmed that DVT patients with silent PE had a higher incidence of symptomatic PE events during the first 15 days than those with no PE (odds ratio, 4.80; 95% CI, 1.27-18.1), with no differences in bleeding. CONCLUSIONS: DVT patients with silent PE at baseline had an increased incidence of symptomatic PE events during the first 15 days of anticoagulant therapy. This effect disappeared after 3 months of anticoagulation

Effects of age on the risk of dying from pulmonary embolism or bleeding during treatment of deep vein thrombosis

BACKGROUND: The risk of patients dying of pulmonary embolism (PE) or bleeding during the treatment of deep vein thrombosis (DVT), and whether these risks are influenced by patient age, has not been thoroughly studied. METHODS: We used data from the Registro Informatizado de la Enfermedad TromboEmb\uf3lica (RIETE) to assess the risk of fatal PE and fatal bleeding in 16,199 patients with lower limb DVT (without symptomatic PE at the time of inclusion) during the 3 months after diagnosis, with patients categorized according to age. RESULTS: During the 3 months of anticoagulant treatment, there were 31 fatal PEs (0.19%) and 83 fatal hemorrhages (0.51%). During the first 7 days of therapy, the frequency of fatal PEs was similar to that of fatal bleeding (12 vs 14 deaths, respectively; odds ratio [OR], 0.86; 95% confidence interval [CI], 0.39-1.87). However, from days 8 to 90, the frequency of fatal bleeding was greater than that of fatal PE (69 vs 19 deaths; OR, 3.64; 95% CI, 2.22-6.20). The higher frequency of fatal bleeding compared with fatal PE from days 8 to 90 appeared to be confined to patients who were aged 65 60 years. Multivariate analysis showed that patient age was independently associated with an increased risk of death from bleeding during the first 3 months: every 10 years the OR increased by 1.37 (95% CI, 1.12-1.67). CONCLUSIONS: During the first week of treatment, the risk of fatal bleeding and fatal PE were similar. Then, particularly in patients who were aged 65 60 years, the risk of dying from bleeding exceeded the risk of dying from PE

Unsuspected pulmonary embolism in patients with cancer

BACKGROUND: The natural history of unsuspected pulmonary embolism (PE) in patients with cancer has not been thoroughly studied. METHODS: We used the RIETE Registry data to compare the clinical characteristics, treatment strategies and outcome in cancer patients with unsuspected PE and in those presenting with symptomatic, acute PE. RESULTS: Up to December 2011, 78 cancer patients with unsuspected PE and 1,994 with symptomatic PE had been enrolled. Patients with unsuspected PE more likely had colorectal cancer than those with symptomatic PE (28% vs. 13%), and less likely had prostate (3.8% vs. 10%) or hematologic (1.3% vs. 6.4%) cancer, or prior venous thromboembolism (3.8% vs. 12%). While the patients were receiving anticoagulant therapy, the incidence of PE recurrences (0% vs. 1.9%) or major bleeding (2.6% vs. 4.8%) were similar. After completion of anticoagulation, recurrent PE developed in 2.6% vs. 1.4% of patients, and major bleeding in 0% vs. 0.4%, respectively. CONCLUSIONS: Our findings suggest that the clinical characteristics and outcome in cancer patients with unsuspected PE are quite similar to those in patients with symptomatic PE

Outcomes in Neurosurgical Patients Who Develop Venous Thromboembolism: A Review of the RIETE Registry

OBJECTIVES: Registro Informatizado de Enfermedad TromboEmb\uf3lica (RIETE) database was used to investigate whether neurosurgical patients with venous thromboembolism (VTE) were more likely to die of bleeding or VTE and the influence of anticoagulation on these outcomes. METHODS: Clinical characteristics, treatment details, and 3-month outcomes were assessed in those who developed VTE after neurosurgery. RESULTS: Of 40 663 patients enrolled, 392 (0.96%) had VTE in less than 60 days after neurosurgery. Most patients in the cohort (89%) received initial therapy with low-molecular-weight heparin, (33% received subtherapeutic doses). In the first week, 10 (2.6%) patients died (8 with pulmonary embolism [PE], no bleeding deaths; P = .005). After the first week, 20 (5.1%) patients died (2 with fatal bleeding, none from PE). Overall, this cohort was more likely to develop a fatal PE than a fatal bleed (8 vs 2 deaths, P = .058). CONCLUSIONS: Neurosurgical patients developing VTE were more likely to die from PE than from bleeding in the first week, despite anticoagulation

Factors Associated with elevated Pulmonary Arterial Pressure Levels on the Echocardiographic Assessment in Patients with Prior Pulmonary Embolism

BACKGROUND: Factors associated with the detection of raised systolic pulmonary artery pressure (sPAP) levels in patients with a prior episode of pulmonary embolism (PE) are not well known. METHODS: We used the RIETE Registry database to identify factors associated with the finding of sPAP levels 6550 mm Hg on trans-thoracic echocardiography, in 557 patients with a prior episode of acute, symptomatic PE. RESULTS: Sixty-two patients (11.1%; 95% CI: 8.72-14.1) had sPAP levels 6550 mm Hg. These patients were more likely women, older, and more likely had chronic lung disease, heart failure, renal insufficiency or leg varicosities than those with PAP levels <50mm Hg. During the index PE event, they more likely had recent immobility, and more likely presented with hypoxemia, increased sPAP levels, atrial fibrillation, or right bundle branch block. On multivariate analysis, women aged 6570 years (hazard ratio [HR]: 2.0; 95% CI: 1.0-3.7), chronic heart or chronic lung disease (HR: 2.4; 95% CI: 1.3-4.4), atrial fibrillation at PE presentation (HR: 2.8; 95% CI: 1.3-6.1) or varicose veins (HR: 1.8; 95% CI: 1.0-3.3) were all associated with an increased risk to have raised sPAP levels. Chronic heart disease, varicose veins, and atrial fibrillation were independent predictors in women, while chronic heart disease, atrial fibrillation, a right bundle branch block or an S1Q3T3 pattern on the electrocardiogram were independent predictors in men. CONCLUSIONS: Women aged 6570 years more likely had raised sPAP levels than men after a PE episode. Additional variables influencing this risk seem to differ according to gender

D-dimer levels and 90-day outcome in patients with acute pulmonary embolism with or without cancer

BACKGROUND: The prognostic value of D-dimer testing in patients with acute pulmonary embolism (PE) has not been thoroughly studied. METHODS: We used the RIETE Registry data to assess the 90-day prognostic value of increased IL Test D-dimer levels at baseline in patients with PE, according to the presence or absence of cancer. RESULTS: As of May 2013, 3,283 patients with acute PE underwent D-dimer testing using IL Test D-dimer. Among 2,588 patients without cancer, those with D-dimer levels in the highest quartile had a higher rate of fatal PE (2.6% vs. 0.9%; p=0.002), fatal bleeding (1.1% vs. 0.3%; p=0.017) and all-cause death (9.1% vs. 4.4%; p<0.001) at 90 days compared with those with levels in the lowest quartiles. Among 695 patients with cancer, those with levels in the highest quartile had a similar rate of fatal PE or fatal bleeding but higher mortality (35% vs. 24%; p<0.01). On multivariate analysis, non-cancer patients with D-dimer levels in the highest quartile had an increased risk for fatal PE (odds ratio [OR]: 3.3; 95% CI: 1.6-6.6), fatal bleeding (OR: 4.3; 95% CI: 1.4-13.7) and all-cause death (OR: 2.1; 95% CI: 1.4-3.1) compared with patients with levels in the lowest quartiles. CONCLUSIONS: Non-cancer patients with acute PE and IL Test D-dimer levels in the highest quartile had an independently higher risk for fatal PE, fatal bleeding and all-cause death at 90 days than those with levels in the lowest quartiles. In patients with cancer, D-dimer levels failed to predict fatal PE or fatal bleeding

Platelet count and outcome in patients with acute venous thromboembolism

The relationship between platelet count and outcome in patients with acute venous thromboembolism (VTE) has not been consistently explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We categorised patients as having very low- (450,000/\ub5l) platelet count at baseline, and compared their three-month outcome. As of October 2012, 43,078 patients had been enrolled in RIETE: 21,319 presenting with pulmonary embolism and 21,759 with deep-vein thrombosis. In all, 502 patients (1.2%) had very low-; 5,472 (13%) low-; 28,386 (66%) normal-; 7,157 (17%) high-; and 1,561 (3.6%) very high platelet count. During the three-month study period, the recurrence rate was: 2.8%, 2.2%, 1.8%, 2.1% and 2.2%, respectively; the rate of major bleeding: 5.8%, 2.6%, 1.7%, 2.3% and 4.6%, respectively; the rate of fatal bleeding: 2.0%, 0.9%, 0.3%, 0.5% and 1.2%, respectively; and the mortality rate: 29%, 11%, 6.5%, 8.8% and 14%, respectively. On multivariate analysis, patients with very low-, low-, high- or very high platelet count had an increased risk for major bleeding (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.85-3.95; 1.43 [1.18-1.72]; 1.23 [1.03-1.47]; and 2.13 [1.65-2.75]) and fatal bleeding (OR: 3.70 [1.92-7.16], 2.10 [1.48-2.97], 1.29 [0.88-1.90] and 2.49 [1.49-4.15]) compared with those with normal count. In conclusion, we found a U-shaped relationship between platelet count and the three-month rate of major bleeding and fatal bleeding in patients with VTE