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Background: Pulmonary embolism (PE) and acute exacerbation of chronic obstructive pulmonary disease (COPD) have similar clinical symptoms, making PE diagnosis challenging. Previous studies have shown that the prevalence of PE among COPD patients admitted with worsening respiratory symptoms was not negligible, but that systematic search for PE did not provide a clinical benefit. Predictive factors for PE remain unknown., Objective: to identify predictive factors for PE among COPD patients with worsening respiratory symptoms., Methods: We conducted an individual participant data meta-analysis which included the patients from the prospective PEP cohort and those randomized to the intervention arm in the SLICE trial which included a systematic search for PE in COPD patients admitted for worsening respiratory symptoms. Univariable and multivariable analysis were used to assess factors associated with the diagnosis of PE during the initial management., Results: Among 1110 COPD patients, PE was diagnosed in 61 (5.49 %; 95 %CI 4.15 %-6.84 %). In univariable analysis, BNP (Brain natriuretic peptide) (odds ratio [OR] 1.02 per 100 ng/L increase, 95 %CI 1.01-1.04), prothrombin time (OR 0.78, 95 %CI 0.65-0.94), fibrinogen (OR 0.80, 95 %CI 0.64-0.98), atrial fibrillation (OR 4.74, 95 %CI 1.84-10.80), respiratory rate ≥30 min (OR 2.34, 95 %CI 1.13-4.6) and recent medical immobilization (OR 1.79, 95 %CI 0.99-3.13]) were associated with the risk of PE diagnosed during the initial management. In multivariable analysis, respiratory rate ≥30 (OR 2.77, 95 %CI 1.08-6.71) was a predictive factor for PE, as well as BNP (OR 1.02, 95 %CI 1.00-1.05) with an area under the curve =0.64, negative predictive value =0.15 (95 %CI 0.09-0.23), sensitivity =0.78 (95 %CI 0.74-0.82) and specificity =0.46 (95 %CI 0.29-0.63)., Conclusion: Among patients with COPD admitted for worsening respiratory symptoms, respiratory rate and BNP levels are predictor of PE, but with limited discriminatory power., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

The transcription of ribosomal RNA (rRNA) by RNA Polymerase I (Pol I) is the rate-limiting step in ribosome biogenesis and a major determinant of cellular growth rates. Unlike other eukaryotes, which express identical rRNA from large tandem arrays of dozens to hundreds of identical rRNA genes in every cell, the genome of the human malaria parasite Plasmodium falciparum contains only a handful single-copy 47S rRNA loci that differ substantially from one another in length, sequence, and expression in different cell types. We found that the growth of the malaria parasite was acutely sensitive to the Pol I inhibitors 9-hydroxyellipticine and BMH-21 and demonstrated that they greatly reduce the transcription of 47S rRNAs as well as the transcription of other non-coding RNA genes. This makes P. falciparum only the second known organism where RNA Polymerase I transcribes genes other than the 47S rRNAs. We found that the various types of Pol I-transcribed genes differed by more than two orders of magnitude in their susceptibility to these inhibitors and explored the implications of these findings for the regulation of rRNA in P. falciparum .

Background and Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic pulmonary hypertension leading to right heart failure and death. While pulmonary endarterectomy is the treatment of choice, some patients might benefit from medical therapy or balloon pulmonary angioplasty. Sex differences in outcomes of these therapies are not well characterized., Material and Methods: We conducted a systematic review and meta-analysis to investigate sex differences in outcomes of various therapies for CTEPH. We searched MEDLINE, PubMed, Embase, CINAHL and the Cochrane Library databases between January 1, 2010 and April 30, 2021, published in English. We pooled incidence estimates using random-effects meta-analyses. We evaluated heterogeneity using the I 2 statistic. We assessed publication bias using Begg's and Egger's tests. This study is registered in PROSPERO, CRD42021268504., Results: A total of 19 studies met the eligibility criteria, but only 3 trials provided separate outcomes for women and men. Two studies evaluated the efficacy of BPA, and one study evaluated the efficacy of riociguat (129 patients). Overall, 57.3% of patients were women and 62.6% were in functional class III. Mean time of follow-up was 55.5 (SD 26.1) weeks. Women showed a significantly better response in cardiac index (mean difference [MD], 0.10L/min/m 2 ; 95% confidence interval [CI], 0.04-0.16; I 2 =0%; P=0.001). Alternatively, the reduction of pulmonary vascular resistances was significantly higher for men than for women (MD, 161.17dynscm -5 ; 95% CI, 67.99-254.35; I 2 =0%; P=0.0007)., Conclusions: Women and men might show different hemodynamic responses to riociguat or BPA for CTEPH., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Transcription of ribosomal RNA (rRNA) by RNA Polymerase I (Pol I) is the rate-limiting step in ribosome biogenesis and a major determinant of cellular growth rates. Unlike virtually every other eukaryote, which express identical rRNA from large tandem arrays of dozens to hundreds of identical rRNA genes in every cell, the genome of the human malaria parasite Plasmodium falciparum contains only a handful single-copy 47S rRNA loci that differ substantially from one another in length, sequence and expression in different cell-types. We found that growth of malaria parasite was acutely sensitive to the Pol I inhibitors 9-hydroxyellipticine and BMH-21 and demonstrate that they greatly reduce the transcription of 47S rRNAs as well as transcription of other non-coding RNA genes. Surprisingly, we found that the various types of Pol I-transcribed genes differed by more than two orders of magnitude in their susceptibility to these inhibitors and explore the implications of these findings for regulation of rRNA in P. falciparum ., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest.

High-risk pulmonary embolism (PE) refers to a large embolic burden causing right ventricular failure and hemodynamic instability. It accounts for approximately 5% of all cases of PE but contributes significantly to overall PE mortality. Systemic thrombolysis is the first-line revascularization therapy in high-risk PE. Surgical embolectomy or catheter-directed therapy is recommended in patients with an absolute contraindication to systemic thrombolysis. Extracorporeal membrane oxygenation (ECMO) provides respiratory and hemodynamic support for the most critically ill PE patients with refractory cardiogenic shock or cardiac arrest. The complex management of these individuals requires urgent yet coordinated multidisciplinary care. In light of existing evidence regarding the utility of ECMO in the management of high-risk PE patients, a number of possible indications for ECMO utilization have been suggested in the literature. Specifically, in patients with refractory cardiac arrest, resuscitated cardiac arrest, or refractory shock, including in cases of failed thrombolysis, venoarterial ECMO (VA-ECMO) should be considered, either as a bridge to percutaneous or surgical embolectomy or as a bridge to recovery after surgical embolectomy. We review here the current evidence on the use of ECMO as part of the management strategy for the highest-risk presentations of PE and summarize the latest data in this indication., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Right ventricle (RV) dysfunction increases the risk of death from pulmonary embolism (PE). C-reactive protein (CRP) might identify RV inflammation and dysfunction in patients with PE., Methods: This cohort study enrolled consecutive stable patients with acute PE between 2017 and 2023. We stratified patients by quartiles of CRP. We evaluated the association between CRP quartiles and the presence of RV dysfunction, and used multivariable models to assess for an association between CRP and the outcomes of all-cause and PE-specific mortality during the 30 days of follow-up after PE diagnosis., Results: The study included 633 stable patients with PE. Patients without RV dysfunction had significantly lower median (IQR) CRP levels compared with patients with RV dysfunction (n=509, 31.7 [10.0-76.4]mg/L vs n=124, 45.4 [16.0-111.4]mg/L; P=0.018). CRP showed a statistically significant positive association with the presence of RV dysfunction (P<0.01). On multivariable analysis, CRP level was not significantly associated with 30-day all-cause mortality (adjusted odds ratio [OR] per mg/L increment, 1.00; 95% CI, 1.00-1.01; P=0.095), but higher CRP was associated with significantly higher PE-related mortality (adjusted OR, 1.01; 95% CI, 1.00-1.01; P=0.026). Compared with patients in CRP quartile 1, patients in quartiles 2, 3, and 4 had a stepwise increase in the adjusted odds of 30-day all-cause death of 2.41 (P=0.148), 3.04 (P=0.062), and 3.15 (P=0.052), respectively., Conclusions: As an indicator of RV dysfunction, CRP may improve risk stratification algorithms for hemodynamically stable patients with acute symptomatic PE., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The effect of a pulmonary embolism response team (PERT) in the short-term prognosis of patients with acute symptomatic pulmonary embolism (PE) lacks clarity. We therefore aimed at evaluating the effect of a PERT team on short-term mortality among patients with acute PE., Methods: We retrospectively reviewed consecutive patients with acute symptomatic PE enrolled in a single-center registry between 2007 and 2022. We used propensity score matching to compare treatment effects for patients with similar predicted probabilities of receiving management by the PERT team. The primary outcome was all-cause mortality within 30 days following the diagnosis of PE. The secondary outcome was 30-day PE-related mortality., Results: Of the 2,902 eligible patients who had acute symptomatic PE, 223 (7.7%; 95% confidence interval [CI], 6.7%-8.7%) were managed by the PERT team. Two hundred and seven patients who were treated by the PERT were matched with 207 patients who were not. Matched pairs did not show a statistically significant lower all-cause (odds ratio [OR], 1.09; 95% CI, 0.63-1.89) or PE-related death (OR, 1.30; 95% CI, 0.47-3.62) for PERT management compared with no PERT management through 30 days after diagnosis of PE., Conclusions: Our results suggest that multidisciplinary care of patients with acute symptomatic PE by a PERT team is not associated with a significant reduction in short-term all-cause or PE-related mortality., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term sequel to pulmonary embolism (PE) whose incidence varies according to different published studies. We have carried out this study to determine its incidence within 2 years after index pulmonary embolism and to study limitations to an early diagnosis., Material and Methods: OSIRIS is a multicentre, longitudinal cohort study. Patients were followed for 3, 6, 12, and 24 months after pulmonary embolism using a structured three-step algorithm. A physician-centered questionnaire at least one positive response in a screening proceeded to the second step, transthoracic echocardiography. The third step consisted of ventilation/perfusion lung scintigraphy and right heart catheterisation. A transthoracic echocardiography was performed in patients without positive response in the screening questionnaire after 2 years. CTEPH diagnosis required haemodynamic confirmation by right heart catheterisation and mismatched perfusion defects on lung scintigraphy., Results: A total of 1191 patients were enrolled in 18 Spanish hospitals. Cumulative CTEPH incidence after 2-years PE was: 2.49 % (95 % CI: 1.68-3.56) and the incidence rate of CTEPH was 1.1 cases per 1000 person-months (95 % CI: 0.725; 1.60). The CTEPH algorithm presented a lack of adherence of 29 %; patient and physician preferences posed barriers to the triage algorithm The screening questionnaire, in patients who completed the follow-up, shows a specificity of 91.3 % (89.0-93.2 %) and negative predictive value of 99.4 % (98.4-99.8 %).., Conclusions: OSIRIS provides practiced clinical based data on the chronic thromboembolic pulmonary hypertension incidence and identified barriers to the implementation of a 3-step triage algorithm for its detection., Clinical Trial Registration: clinicaltrials.gov identifier: NCT03134898., Competing Interests: Declaration of competing interest Authors declared to have no conflicts., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Neurovascular coupling (NVC) is the ability to locally adjust vascular resistance as a function of neuronal activity. Recent experiments have illustrated that NVC is partially independent of metabolic signals. In addition, nitric oxide (NO) has been shown in some instances to provide an important mechanism in altering vascular resistance. An extension to the original model of NVC [1] has been developed to include the activation of both somatosensory neurons and GABAergic interneurons and to investigate the role of NO and the delicate balance of GABA and neuronal peptide enzymes (NPY) pathways. The numerical model is compared to murine experimental data that provides time-dependent profiles of oxy, de-oxy, and total-hemoglobin. The results indicate a delicate balance that exists between GABA and NPY when nNOS interneurons are activated mediated by NO. Whereas somatosensory neurons (producing potassium into the extracellular space) do not seem to be effected by the inhibition of NO. Further work will need to be done to investigate the role of NO when stimulation periods are increased substantially from the short pulses of 2 s as used in the above experiments., (Copyright © 2023 by ASME.)

Objectives: The aim of this study was to assess the performance of the National Early Warning Score 2 (NEWS2) in predicting a short-term complicated outcome in stable patients with acute symptomatic pulmonary embolism (PE). We also studied the ability of the NEWS2 score compared with the simplified Pulmonary Embolism Severity Index (sPESI) for identifying low-risk patients with acute PE., Methods: We performed a retrospective analysis of a prospective cohort composed of 848 patients with acute PE. The NEWS2 and the sPESI were calculated for each patient according to different clinical variables. We assessed the predictive accuracy of these scores for a 30-day complicated outcome using the C statistic, which was obtained by logistic regression models and ROC curves. We also assessed the test and performance characteristics of the low-risk versus high-risk categories of each prediction rule., Results: Overall, 63 out of 848 patients died (7.4%; 95% confidence interval, 5.7%-9.2%) during the first month of follow-up. Both scores showed a similarly poor predictive value for 30-day complicated outcome (C statistic, 0.68 and 0.62). The sPESI classified fewer patients as low-risk (36.9% versus 44.5%; P<0.01). Compared with the NEWS2 score, the sPESI showed significantly higher sensitivity (92.1% versus 66.7%) and a better negative predictive value (98.4% versus 94.4%)., Conclusion: Both scores provide similar information for stratifying the risk of a complicated outcome in stable patients with PE. The sPESI identified low-risk patients with PE better than the NEWS2 score., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: For patients with suspected pulmonary embolism (PE), age- or clinically-adjusted D-dimer threshold level can be used to define a negative test that safely excludes PE and reduces the use of imaging. However, the utility of this approach in patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbation is undefined., Methods: We ran an analysis of the patients hospitalized for COPD exacerbation and randomized to the intervention in the SLICE trial. Using the conventional strategy as the reference, we compared the proportion of patients with a negative D-dimer result, and the negative predictive value and sensitivity of three D-dimer threshold strategies for initial PE or subsequent diagnosis of venous thromboembolism (VTE): the age-adjusted strategy, the Wells-adjusted strategy, and the YEARS-adjusted strategy., Results: We included 368 patients. Using a conventional threshold, 182 (49.5%) patients had negative D-dimer values, of whom 1 (0.6%) had PE (sensitivity, 94.1%). The use of an age-adjusted threshold increased the number of patients in whom PE could be excluded from 182 to 233 patients (63.3%), and the proportion of false-negative findings increased from 0.5% to 1.7% (sensitivity, 76.5%). With the use of the Wells or YEARS strategies, 64.4% and 71.5% had negative values, and the proportion of false-negative findings was 2.5% (sensitivity, 64.7%) and 2.7% (sensitivity, 58.8%), respectively., Conclusions: In patients hospitalized for COPD exacerbation, compared with the conventional strategy, age- or clinically-adjusted strategies of D-dimer interpretation were associated with a larger proportion of patients in whom PE was ruled out with a higher failure rate., Trial Registration: ClinicalTrials.gov number: NCT02238639 ., (© 2022. The Author(s).)

Porous materials, such as zeolites and metal-organic frameworks (MOFs), and zeolitic-organic frameworks (ZIFs), are frequently considered for shape-selective separations, molecular storage, and catalysis applications, mainly due to their hollow structures. The amount and chemical nature of sorbate molecules that may (or may not) be fitted inside their cavities, and hence the bulk of their applications, depend on their internal structure, that is, on their surface areas, available volumes, and shapes of their porosities. However, experimentally, the access to such strucutral information is somewhat limited and computationally can be expensive to calculate for structures of more than 100 atoms. Moreover, the large number of known and hypothetical structures reported makes computational geometry-based techniques particularly attractive to identify the most suitable structures for a desired application. In this context, Delta Chem is both a method and a program designed to quickly analyze porous structures, relying solely on their Cartesian coordinates, and characterize the shapes of their cages using regular convex polyhedra. The program also provides a systematic approach to determine the positions of the centers of porosity and the atoms that contribute to form the internal surfaces of these materials, as well as other geometric features of the porosities such as volumes and surface areas. It also includes a routine to compute the irreducible volumes of the cages, i.e., minimal regions of the cavities that can be used to represent the hole porosity shape via symmetry operations. The capabilities of the program are tested on well-studied porous systems, namely, Buckminsterfullerene, MOF-5, HKUST-1, UiO-66, and ZIF-8. As highlighted through the fullerene, it can equally be used to characterize the cavities of hollow molecules. Our approach is compared against other widely used polyhedra-based approaches for porous materials. Our results show that Delta Chem is a novel and systematic way of characterizing routinely porous materials and hollow molecules. Besides potential applications to systematically simplify computational studies of shape-dependent properties, like shape-selective catalysis and adsorption, Delta Chem can be used in many studies to generate basic geometrical models.

Background: The length of hospital stay (LOS) for acute pulmonary embolism (PE) varies considerably. Whether the upfront use of a PE prognostic assessment and management pathway is effective in reducing the LOS remains unknown., Methods: We conducted a randomised controlled trial of adults hospitalised for acute PE: patients were assigned either to a prognostic assessment and management pathway involving risk stratification followed by predefined criteria for mobilisation and discharge (intervention group) or to usual care (control group). The primary end-point was LOS. The secondary end-points were the cost of prognostic tests and of hospitalisation, and 30-day clinical outcomes., Results: Of 500 patients who underwent randomisation, 498 were included in the modified intention-to-treat analysis. The median LOS was 4.0 days (interquartile range (IQR) 3.7-4.2 days) in the intervention group and 6.1 days (IQR 5.7-6.5 days) in the control group (p<0.001). The mean total cost of prognostic tests was EUR 174.76 in the intervention group, compared with EUR 233.12 in the control group (mean difference EUR -58.37, 95% CI EUR -84.34- to -32.40). The mean total hospitalisation cost per patient was EUR 2085.66 in the intervention group, compared with EUR 3232.97 in the control group (mean difference EUR -1147.31, 95% CI EUR -1414.97- to -879.65). No significant differences were observed in 30-day readmission (4.0% versus 4.8%), all-cause mortality (2.4% versus 2.0%) or PE-related mortality (0.8% versus 1.2%) rates., Conclusions: The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE., Competing Interests: Conflict of interest: D. Jiménez has served as an advisor or consultant for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, Pfizer, ROVI and Sanofi; served as a speaker or a member of a speakers’ bureau for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, ROVI and Sanofi; and has received grants for clinical research from Daiichi Sankyo, Sanofi and ROVI. Conflict of interest: C. Rodríguez has nothing to disclose. Conflict of interest: F. León has nothing to disclose. Conflict of interest: L. Jara-Palomares has served as an advisor or consultant for Actelion Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Leo Pharma, Menarini, Pfizer, GSK and ROVI. Conflict of interest: R. López-Reyes has nothing to disclose. Conflict of interest: P. Ruiz-Artacho has nothing to disclose. Conflict of interest: T. Elías has nothing to disclose. Conflict of interest: R. Otero has served as an advisor or consultant for Bayer HealthCare Pharmaceuticals, Leo Pharma, Janssen Pharmaceutical Companies, Merck Sharp & Dohme Corp, ROVI and Sanofi; and received grants for clinical research from Leo Pharma and Bayer Hispania SL. Conflict of interest: A. García-Ortega has nothing to disclose. Conflict of interest: A. Rivas-Guerrero has nothing to disclose. Conflict of interest: J. Abelaria has nothing to disclose. Conflict of interest: S. Jiménez has nothing to disclose. Conflict of interest: A. Muriel has nothing to disclose. Conflict of interest: R. Morillo has nothing to disclose. Conflict of interest: D. Barrios has nothing to disclose. Conflict of interest: R. Le Mao has nothing to disclose. Conflict of interest: R.D. Yusen has received research funding from Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Pfizer and Portola in the past 3 years; and has served as a consultant for Bayer HealthCare, Inc., Bristol-Myers Squibb, GlaxoSmithkline, Janssen, Johnson and Johnson, Ortho Pharmaceuticals, Organon, Pfizer, Portola, Sanofi and SCIOS in the past 3 years. Conflict of interest: B. Bikdeli reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of inferior vena cava filters. Conflict of interest: M. Monreal has served as an advisor or consultant for Bayer HealthCare Pharmaceuticals, Daiichi Sankyo, Leo Pharma and Sanofi; served as a speaker or a member of a speakers’ bureau for Bayer HealthCare Pharmaceuticals, Daiichi Sankyo, Leo Pharma and Sanofi; and received grants for clinical research from Sanofi and Bayer. Conflict of interest: J.L. Lobo has nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: The novel disease caused by the new coronavirus SARS-CoV-2 has caused an unprecedented global pandemic. Care providers of asthmatic children are increasingly con-cerned; as viral infections are one of the primary triggers of asthma flare-up. However, the effect of SARS-CoV-2 as well as the generated worldwide lockdown on asthmatic children is unknown., Objective: The aim of this study was to analyze the effects of pandemic SARS-CoV-2 in pediat-ric asthma control., Material and Methods: A retrospective, open, transversal study was performed at five ter-tiary hospitals. Recruited patients were aged <18 years and had physician-diagnosed asthma. Information regarding the 2019 and 2020 seasons were provided., Results: Data were collected from 107 children (age range: 3-18 years, mean age: 12 years). Well-controlled asthma was observed in 58 (54.2%) patients in 2020 versus 30 (28%) in 2019, and 15 (14%) patients had poorly controlled asthma in 2020 versus 28 (26.2%) in 2019. In 2020, a decrease in exacerbations caused by allergies to pollen, dust mites, molds, and through other causes not related to SARS-CoV-2 infection was observed. An increase in exacerbations was observed due to animal dander, stress, physical exercise, and SARSCoV-2 infection. Children had a reduced need for asthma-controlling medication, made fewer visits to healthcare providers and had lesser need of treatment with oral corticosteroids if compared with the same season of 2019., Conclusion: Pediatric asthma control improved, the need for controller medication declined, and fewer visits to healthcare providers were made during the pandemic if compared with the 2019 season., Competing Interests: The authors declare no potential conflicts of interest regarding research, authorship, and/or publication of this article.

Background: Oral immunotherapy is a frequent treatment for the management of food allergies, but adverse events (AE) are common. This study assessed the outcome of cow's milk oral immunotherapy (MOIT) in severe cow`s milk-allergic patients treated with omalizumab in a real-life setting., Methods: OmaBASE was a national, multicenter, open, and observational registry that collected clinical, immunologic, and treatment from patients with food allergy receiving omalizumab., Results: Data derived from 58 patients aged 10.3 years (IQR 6.3-13.2) and median milk-specific IgE 100 kU A /L at the start of omalizumab treatment. Most had experienced anaphylaxis by accidental exposures (70.7%) and had asthma (81.0%). Omalizumab in monotherapy induced tolerance to ≥6000 mg of cow's milk protein (CMP) to 34.8% of patients tested by oral food challenge. Omalizumab combined with MOIT conferred desensitization to ≥6000 mg of CMP to 83.0% of patients. Omalizumab withdrawal triggered more AE (P = .013) and anaphylaxis (P = .001) than no discontinuation. Anaphylaxis was observed in 36.4% of patients who discontinued omalizumab, and more in those with sudden (50.0%) rather than progressive (12.5%) discontinuation. At database closure, 40.5% of patients who had completed follow-up tolerated CMP without omalizumab (7.2% 1500-4500 mg; 33.3% ≥6000 mg)., Conclusion: Milk oral immunotherapy initiated under omalizumab allows the desensitization of subjects with severe cow's milk allergy even after omalizumab discontinuation. However, discontinuation of omalizumab can lead to severe AE and should be carefully monitored., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Case: A 19 year-old male patient presented with testicular dislocation after abdominopelvic trauma. During open reduction and internal fixation, consult to urology was placed after discovering the presence of the intra-abdominal testicle. The testicle was repositioned into the scrotum with orchiopexy, and pelvic fixation was completed with 1 sacroiliac percutaneous screw and pubic symphysis fixation. Postoperative recovery was uneventful, and the patient was discharged home on postoperative day 3., Conclusion: Testicular dislocation is an uncommon finding after blunt abdominopelvic trauma; hence, it may be overlooked. Prompt diagnosis of testicular dislocation given the need for operative management to preserve testicle viability is crucial., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B554)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Objective: To evaluate the utility of a modified (i.e., without the variable "Age >80 years") simplified Pulmonary Embolism Severity Index (sPESI) in elderly patients with acute symptomatic pulmonary embolism (PE), and to derive and validate a refined version of the sPESI for identification of elderly patients at low risk of adverse events., Methods: The study included normotensive patients aged >80 years with acute PE enrolled in the RIETE registry. We used multivariable logistic regression analysis to create a new risk score to predict 30-day all-cause mortality. We externally validated the new risk score in elderly patients from the COMMAND VTE registry., Results: Multivariable logistic regression identified four predictors for mortality: high-risk sPESI, immobilization, coexisting deep vein thrombosis (DVT), and plasma creatinine >2 mg/dL. In the RIETE derivation cohort, the new model classified fewer patients as low risk (4.0% [401/10,106]) compared to the modified sPESI (35% [3522/10,106]). Low-risk patients based on the new model had a lower 30-day mortality than those based on the modified sPESI (1.2% [95% CI, 0.4-2.9%] versus 4.7% [95% CI, 4.0-5.4%]). In the COMMAND VTE validation cohort, 1.5% (3/206) of patients were classified as having low risk of death according to the new model, and the overall 30-day mortality of this group was 0% (95% CI, 0-71%), compared to 5.9% (95% CI, 3.1-10.1%) in the high-risk group., Conclusions: For predicting short-term mortality among elderly patients with acute PE, this study suggests that the new model has a substantially higher sensitivity than the modified sPESI. A minority of these patients might benefit from safe outpatient therapy of their disease., (Copyright © 2021. Published by Elsevier B.V.)

Recent studies have demonstrated that geographic location features collected using smartphones can be a powerful predictor for depression. While location information can be conveniently gathered by GPS, typical datasets suffer from significant periods of missing data due to various factors (e.g., phone power dynamics, limitations of GPS). A common approach is to remove the time periods with significant missing data before data analysis. In this paper, we develop an approach that fuses location data collected from two sources: GPS and WiFi association records, on smartphones, and evaluate its performance using a dataset collected from 79 college students. Our evaluation demonstrates that our data fusion approach leads to significantly more complete data. In addition, the features extracted from the more complete data present stronger correlation with self-report depression scores, and lead to depression prediction with much higher F 1 scores (up to 0.76 compared to 0.5 before data fusion). We further investigate the scenerio when including an additional data source, i.e., the data collected from a WiFi network infrastructure. Our results show that, while the additional data source leads to even more complete data, the resultant F 1 scores are similar to those when only using the location data (i.e., GPS and WiFi association records) from the phones.

Depression is a serious mental health problem. Recently, researchers have proposed novel approaches that use sensing data collected passively on smartphones for automatic depression screening. While these studies have explored several types of sensing data (e.g., location, activity, conversation), none of them has leveraged Internet traffic of smartphones, which can be collected with little energy consumption and the data is insensitive to phone hardware. In this paper, we explore using coarse-grained meta-data of Internet traffic on smartphones for depression screening. We develop techniques to identify Internet usage sessions (i.e., time periods when a user is online) and extract a novel set of features based on usage sessions from the Internet traffic meta-data. Our results demonstrate that Internet usage features can reflect the different behavioral characteristics between depressed and non-depressed participants, confirming findings in psychological sciences, which have relied on surveys or questionnaires instead of real Internet traffic as in our study. Furthermore, we develop machine learning based prediction models that use these features to predict depression. Our evaluation shows that Internet usage features can be used for effective depression prediction, leading to F 1 score as high as 0.80., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Purpose: In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use., Methods: Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription., Results: There are several protocols for systematizing the deprescribing process. The most widely used tool is the Medication Regimen Complexity Index, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication., Conclusions: The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.

Among patients with pulmonary embolism (PE), various permutations of normal or abnormal cardiac troponin results and normal or abnormal echocardiographic right ventricular function are encountered in clinical practice. We aimed to explore whether there is a true gradient of risk based on troponin and echocardiographic results. This study included normotensive patients with PE from the PROgnosTic valuE of CT scan in hemodynamically stable patients with acute symptomatic pulmonary embolism (PROTECT) study. Patients were categorized as having -Troponin/-Echo, -Troponin/+Echo, +Troponin/-Echo, and +Troponin/+Echo. The primary outcome was 30-day "complicated course," including death from any cause, hemodynamic collapse, or recurrent PE. Secondary outcomes included individual adverse event rates. Of the 834 patients who had echocardiographic and troponin results, 569 patients (68%) had -Troponin/-Echo, 126 patients (15%) had -Troponin/+Echo, 74 patients (8.9%) had +Troponin/-Echo, and 65 patients (7.8%) had +Troponin/+Echo. The incidence of 30-day complicated course was 4.6% in patients with -Troponin/-Echo, 11.9% in patients with -Troponin/+Echo, 13.5% in patients with +Troponin/-Echo, and 16.9% in patients with +Troponin/+Echo (P for trend <0.001). In the subgroup of patients with a high-risk sPESI (i.e., intermediate-risk according to the ESC guidelines) (n = 527), the incidence of 30-day complicated course was 14.9% in patients with -Troponin/+Echo, 18.5% in patients with +Troponin/-Echo, and 17.5% in patients with +Troponin/+Echo (P for trend <0.01). In patiens with PE, there seems to be a risk gradient based on troponin and echocardiographic results. This study did not detect a significant risk difference in those with +Troponin/-Echo compared with -Troponin/+Echo.

Limited information exists about the prevalence, management, and outcomes of intermediate-high risk patients with acute pulmonary embolism (PE). In a prospective cohort study, we evaluated consecutive patients with intermediate-high risk PE at a large, tertiary, academic medical center between January 1, 2015 and March 31, 2019. Adjudicated outcomes included PE-related mortality and a complicated course through 30 days after initiation of PE treatment. Repeat systolic blood pressure (SBP), heart rate (HR), brain natriuretic peptide (BNP), and cardiac troponin I (cTnI) measurements, and echocardiography were performed within 48 hours after diagnosis. Among 1,015 normotensive patients with acute PE, 97 (9.6%) had intermediate-high risk PE. A 30-day complicated course and 30-day PE-related mortality occurred in 23 (24%) and 7 patients (7.2%) with intermediate-high risk PE. Seventeen (18%) intermediate-high risk patients received reperfusion therapy. Within 48 hours after initiation of anticoagulation, normalization of SBP, HR, cTnI, BNP, and echocardiography occurred in 82, 86, 78, 72, and 33% of survivors with intermediate-high risk PE who did not receive immediate thrombolysis. A complicated course between day 2 and day 30 after PE diagnosis for the patients who normalized SBP, HR, cTnI, BNP, and echocardiography measured at 48 hours occurred in 2.9, 1.4, 4.5, 3.3, and 14.3%, respectively. Intermediate-high risk PE occurs in approximately one-tenth of patients with acute symptomatic PE, and is associated with high morbidity and mortality. Normalization of HR 48 hours after diagnosis might identify a group of patients with a very low risk of deterioration during the first month of follow-up., Competing Interests: Conflict of Interest None declared.

Objective: To determine the comorbidity and potential for drug-drug interactions (DDIs) among pangenotypic direct-acting-antivirals (pDAAs) and the concomitant medications associated with chronic hepatitis C (CHC) patients in routine clinical practice in Spain., Methods: Retrospective observational study. Included patients were ≥18 years, diagnosed with CHC, on antiviral treatment and required medical attention during 2017. Two groups were differentiated according to age ranges (<50 and ≥50 years). The variables collected were: age, gender, general/specific comorbidity, concomitant medication and potential DDIs (www.hep-druginteractions.org). The pDAAs analysed were: a) Sofosbuvir/Velpatasvir (SOF/VEL), b) Glecaprevir/Pibrentasvir (GLE/PIB) and c) Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX). Bivariate statistical analysis, P<.05., Results: 3,430 patients with a mean age of 56.9 years and 60.3% males were enrolled. The average Charlson index was 0.8. Age range distribution: 18-49 years (28.9%) and ≥50 years (71.1%). The average number of medications per patient/year was 3.1 (SD 2.6). The total percentage of potential DDIs was: 8.6% minor DDIs, 40.5% clinically significant DDIs and 10.0% contraindicated medication. These DDIs were greater in patients ≥50 years (8.6%, 43.8% and 12.4%, respectively, P<.001). For all ages, SOF/VEL showed a lower percentage of: minor interactions (1.3% vs. 6.6% and 5.9%, P<.001); clinically significant interactions (53.4%, vs. 77.4% and 66.3%, P<.001) and contraindicated medication (1.7% vs. 8.3% and 10.7%, P<.001) compared to GLE/PIB and SOF/VEL/VOX, respectively., Conclusions: Patients with CHC present high comorbidity and concomitant medication use, particularly elderly patients, thus implying a greater exposure to potential DDIs. Although the DDI rate was considerable with the three combinations analysed, SOF/VEL showed a lower number of clinically significant interactions., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

The analysis of the available databases related to HIV/AIDS confirms a paradigm shift in the patient's life expectancy: now HIV has become a chronic disease, so patients are aging. However, this advance is accompanied by a negative counterpart: due to the increase in the number of years of life gained, there is a prevalence of comorbidities greater than the general population and at an earlier age. Reducing the risk associated with all the comorbidities that the ageing patient with HIV/AIDS may develop, must now be a health objective; it must be added to the traditional objectives that until now were part of the strategy to reduce the impact of the HIV infection. In the specific case of women, it is also necessary to train peri and postmenopausal women to increase their skills and motivation to care for their health; It is also very important to examine the role that hormone replacement therapy can play in reducing their symptoms.

Background and Objective: To determine the accuracy of clinical gestalt to identify patients with acute symptomatic pulmonary embolism (PE) at low-risk for short-term complications., Patients and Methods: This study included a total of 154 consecutive patients diagnosed with acute symptomatic PE in a tertiary university hospital. We compared the prognostic accuracy of the Pulmonary Embolism Severity Index (PESI), the simplified PESI (sPESI), and clinical gestalt of 1) 2senior physicians (one with and one without experience in the management of patients with PE), 2) a fourth-year resident of Pneumology, 3) a third-year resident of Pneumology, and 4) a second-year resident of Pneumology. The primary outcome was all-cause mortality during the first month after the diagnosis of PE., Results: Thirty-day all-cause mortality was 8.4% (13/154; 8.4%; 95% confidence interval [CI], 4.1-12.8%). The PESI and clinical gestalt classified more patients as low-risk, compared to the sPESI (36.4%, 31.3% y 28.6%, respectively). There were no deaths in the sPESI low-risk category (negative predictive value 100%). Prognostic accuracy increased with increasing experience (84.6 vs. 92.3%; P=.049)., Conclusions: The sPESI showed the best accuracy at correctly identifying low-risk patients with acute symptomatic PE. Clinical gestalt is not inferior to standardized clinical prediction rules to prognosticate patients with acute PE., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Background: Diagnostic guidelines for penicillin allergy in children recommend cumbersome protocols based partially on data from adults, which may be suboptimal for pediatric use., Objective: To assess the accuracy of tools for diagnosis of penicillin allergy in children., Methods: A prospective, multicenter study was conducted in children with reported adverse events related to penicillin, excluding severe reactions. All patients underwent a uniform diagnostic protocol that consisted of clinical history, skin tests, serum specific IgE (sIgE), and, regardless of these results, drug provocation tests (DPTs)., Results: A total of 732 children (mean age, 5.5 years; 51.2% males) completed the allergy workup, including DPTs. Amoxicillin triggered 96.9% of all reactions. None of the patients with an immediate index reaction (IR) developed a reaction on DPT. Penicillin allergy was confirmed in 35 children (4.8%): 6 immediate reactions (17%) and 29 nonimmediate reactions (83%) on the DPT. No severe reactions were recorded. The allergist diagnosis based on the clinical history was not associated with the DPT final outcome. In 30 of 33 allergic patients (91%), the results of all skin tests and sIgE tests were negative. A logistic regression model identified the following to be associated with penicillin allergy: a family history of drug allergy (odds ratio [OR], 3.03; 95% confidence interval [CI], 1.33-6.89; P = .008), an IR lasting more than 3 days vs 24 hours or less (OR, 8.96; 95% CI, 2.01-39.86; P = .004), and an IR treated with corticosteroids (OR, 2.68; 95% CI, 1.30-5.54; P = .007)., Conclusion: Conventional predictors of allergy to penicillin performed weakly. The authors propose straightforward penicillin provocation testing in controlled, experienced centers for the diagnosis of nonsevere penicillin allergy in children., (Copyright © 2018 American College of Allergy, Asthma 8 Immunology. Published by Elsevier Inc. All rights reserved.)

The impact of adherence to published guidelines on the outcomes of patients with acute pulmonary embolism (PE) has not been well defined by previous studies.In this prospective cohort study of patients admitted to a respiratory department (n=2096), we evaluated whether patients with PE had better outcomes if they were acutely managed according to international guidelines. Outcomes consisted of all-cause mortality, PE-related mortality, recurrent venous thromboembolism (VTE) and major bleeding events during the first month of follow-up after diagnosis.Overall, 408 patients (19% (95% CI 18-21%)) did not receive guideline-adherent PE management. Patients receiving non-adherent management were significantly more likely to experience all-cause mortality (adjusted odds ratio (OR) 2.39 (95% CI 1.57-3.61) or PE-related mortality (adjusted OR 5.02 (95% CI 2.42-10.42); p<0.001) during follow-up. Non-adherent management was also a significant independent predictor of recurrent VTE (OR 2.19 (95% CI 1.11-4.32); p=0.03) and major bleeding (OR 2.65 (95% CI 1.66-4.24); p<0.001). An external validation cohort of 34 380 patients with PE from the RIETE registry confirmed these findings.PE management that does not adhere to guidelines for indications related to anticoagulation, thrombolytics and inferior vena cava filters is associated with worse patient outcomes., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2018.)

Objectives: To identify the independent risk factors of primary non-adherence to chronic concomitant treatment in HIV-positive patients, and to measure primary and secondary non-adherence rates to chronic treatments, and secondary non-adherence to antiretroviral therapy and the prevalence of concomitant chronic diseases., Methods: We conducted a retrospective study that included HIV-infected patients with antiretroviral treatmentwho attended the pharmaceutical care office between January and December 2012. The dependent variable was primary non-adherence to concomitant prescription drugs for chronic diseases. To know the predictors of concomitant primary non-adherence, we performed a univariate analysis and a multivariate binary logistic regression model to identify the independent predictors of primary non-adherence to co-medication., Results: Out of 598 patients analysed, 333 patients had a new co-medication prescribed during the studied period. The number of comorbidities per patient was 2.3 and the patients were treated with an average of 3.4 drugs. The rates of primary and secondary non-adherence to co-medication were 8.4% and 44.4%, respectively. The co-occurrence of primary and secondary non-adherence was 24.9%. The number of comorbidities (p=0.001) and co-medications (p=0.001) was significantly higher in patients who had primary non-adherence to co-medication. Furthermore, there was a statistically significant relationship between primary non-adherence and patients treated with psychotropic drugs (p=0.03). The multivariate analysis showed the independent predictor of primary non-adherence to co-medication was the number of co-medications (p<0.001)., Conclusion: One-third of new concomitant medications prescribed to HIV-positive patients were never filled from the pharmacy. The number of co-medications was identified as a predictor of primary non-adherence to chronic concomitant treatment in HIV-infected population.

Background: We aimed to review the efficacy and safety of recanalisation procedures for the treatment of PE., Methods: We searched PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science and CINAHL databases from inception through 31 July 2015 and included randomised clinical trials that compared the effect of a recanalisation procedure versus each other or anticoagulant therapy in patients diagnosed with PE. We used network meta-analysis and multivariate random-effects meta-regression to estimate pooled differences between each intervention and meta-regression to assess the association between trial characteristics and the reported effects of recanalisation procedures versus anticoagulation., Results: For all-cause mortality, there were no significant differences in event rates between any of the recanalisation procedures and anticoagulant treatment (full-dose thrombolysis: OR 0.60; 95% CI0.36 to 1.01; low-dose thrombolysis: 0.47; 95% CI 0.14 to 1.59; and catheter-associated thrombolysis: 0.31; 95% CI 0.01 to 7.96). Full-dose thrombolysis increased the risk of major bleeding (2.00; 95% CI 1.06 to 3.78) compared with anticoagulation. Catheter-directed thrombolysis was associated with the lowest probability of dying (surface under the cumulative ranking curve (SUCRA), 0.67), followed by low-dose thrombolysis (SUCRA, 0.66) and full-dose thrombolysis (SUCRA, 0.55). Similarly, low-dose thrombolysis was associated with the lowest probability of major bleeding (SUCRA, 0.61), followed by catheter-directed thrombolysis (SUCRA, 0.54) and full-dose thrombolysis (SUCRA, 0.17). The results were similar in sensitivity analyses based on restricting only to studies in haemodynamically stable patients with PE., Conclusions: In the treatment of PE, recanalisation procedures do not seem to offer a clear advantage compared with standard anticoagulation. Low-dose thrombolysis was associated with the lowest probability of dying and bleeding., Trial Registration Number: PROSPERO CRD42015024670., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

To externally validate the prognostic impact of copeptin, either alone or integrated in risk stratification models, in pulmonary embolism (PE), we performed a post hoc analysis of 843 normotensive PE patients prospectively included in three European cohorts.Within the first 30 days, 21 patients (2.5%, 95% CI 1.5-3.8) had an adverse outcome and 12 (1.4%, 95% CI 0.7-2.5) died due to PE. Patients with copeptin ≥24 pmol·L -1 had a 6.3-fold increased risk for an adverse outcome (95% CI 2.6-15.5, p<0.001) and a 7.6-fold increased risk for PE-related death (95% CI 2.3-25.6, p=0.001). Risk classification according to the 2014 European Society of Cardiology (ESC) guideline algorithm identified 248 intermediate-high-risk patients (29.4%) with 5.6% (95% CI 3.1-9.3) at risk of adverse outcomes. A stepwise biomarker-based risk assessment strategy (based on high-sensitivity troponin T, N-terminal pro-brain natriuretic peptide and copeptin) identified 123 intermediate-high-risk patients (14.6%) with 8.9% (95% CI 4.5-15.4) at risk of adverse outcomes. The identification of patients at higher risk was even better when copeptin was measured on top of the 2014 ESC algorithm in intermediate-high-risk patients (adverse outcome OR 11.1, 95% CI 4.6-27.1, p<0.001; and PE-related death OR 13.5, 95% CI 4.2-43.6, p<0.001; highest risk group versus all other risk groups). This identified 85 patients (10.1%) with 12.9% (95% CI 6.6-22.0) at risk of adverse outcomes and 8.2% (95% CI 3.4-16.2) at risk of PE-related deaths.Copeptin improves risk stratification of normotensive PE patients, especially when identifying patients with an increased risk of an adverse outcome., Competing Interests: Conflict of interest: K. Hellenkamp reports grants from BRAHMS GmbH, part of Thermo Fisher Scientific, Hennigsdorf/Berlin, Germany, during the conduct of the study. Conflict of interest: P. Pruszczyk has nothing to disclose. Conflict of interest: D. Jiménez has nothing to disclose. Conflict of interest: A. Wyzgal has nothing to disclose. Conflict of interest: D. Barrios has nothing to disclose. Conflict of interest: M. Ciurzynski has nothing to disclose. Conflict of interest: R. Morillo has nothing to disclose. Conflict of interest: L. Hobohm reports grants from the German Federal Ministry of Education and Research (BMBF 01EO1503), during the conduct of the study. Conflict of interest: K. Keller reports grants from the German Federal Ministry of Education and Research (BMBF 01EO1503), during the conduct of the study. Conflict of interest: K. Kurnicka has nothing to disclose. Conflict of interest: M. Kostrubiec has nothing to disclose. Conflict of interest: R. Wachter reports grants from BRAHMS GmbH, part of Thermo Fisher Scientific, Hennigsdorf/Berlin, Germany, during the conduct of the study; personal fees and other from CVRx; grants, personal fees and other from Boehringer Ingelheim; personal fees and other from Bayer; personal fees and other from Servier; personal fees and other from Novartis; other from Johnson and Johnson; grants from European Union; grants from Bundesministerium für Bildung und Forschung; personal fees from Pfizer; and personal fees and other from Medtronic, outside the submitted work. Conflict of interest: G. Hasenfuß reports grants from BRAHMS GmbH, part of Thermo Fisher Scientific, Hennigsdorf/Berlin, Germany, during the conduct of the study; other from Servier, other from Impulse Dynamics, other from Novartis, other from AstraZeneca, other from Corvia, and other from Vifor Pharma, outside the submitted work. Conflict of interest: S. Konstantinides reports grants and personal fees from Bayer HealthCare, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Actelion, grants from Daiichi Sankyo, grants and personal fees from Pfizer-Bristol-Myers Squibb, and personal fees from MSD, outside the submitted work. Conflict of interest: M. Lankeit reports grants from German Federal Ministry of Education and Research (BMBF 01EO1503) and grants from BRAHMS GmbH, part of Thermo Fisher Scientific, Hennigsdorf/Berlin, Germany, during the conduct of the study; personal fees from Actelion, personal fees from Bayer, personal fees from Daiichi Sankyo, personal fees from MSD, and personal fees from Pfizer-Bristol-Myers Squibb, outside the submitted work., (Copyright ©ERS 2018.)

Background: In patients with acute pulmonary embolism (PE), studies have shown an association between coexisting deep vein thrombosis (DVT) and short-term prognosis. It is not known whether complete compression ultrasound testing (CCUS) improves the risk stratification of their disease beyond the recommended prognostic models., Methods: We included patients with normotensive acute symptomatic PE and prognosticated them with the European Society of Cardiology (ESC) risk model for PE. Subsequently, we determined the prognostic significance of coexisting DVT in patients with various ESC risk categories. The primary endpoint was a complicated course after the diagnosis of PE, defined as death from any cause, haemodynamic collapse, or adjudicated recurrent PE., Results: According to the ESC model, 37% of patients were low-risk, 56% were intermediate-low risk, and 6.7% were intermediate-high risk. CCUS demonstrated coexisting DVT in 375 (44%) patients. Among the 313 patients with low-risk PE, coexisting DVT (46%) did not show a significant increased risk of complicated course (2.8%; 95% confidence interval [CI], 0.8%-7.0%), compared with those without DVT (0.6%; 95% CI, 0%-3.2%), (P = 0.18). Of the 478 patients with intermediate-low risk PE, a complicated course was 14% and 6.8% for those with and without DVT, respectively (P = 0.01). Of the 57 patients that had intermediate-high risk PE, a complicated course occurred in 17% and 18% for those with and without DVT, respectively (P = 1.0)., Conclusions: In normotensive patients with PE, testing for coexisting DVT might improve risk stratification of patients at intermediate-low risk for short-term complications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

For patients who have acute symptomatic pulmonary embolism (PE), risk of short-term death and adverse outcomes should drive the initial treatment decisions. Practice guidelines recommend that patients who have a high-risk of PE-related death and adverse outcomes, determined by the presence of haemodynamic instability (i.e., shock or hypotension), should receive systemically administered thrombolytic therapy. Intermediate-high risk patients might benefit from close observation, and some should undergo escalation of therapy beyond standard anticoagulation, particularly if haemodynamic deterioration occurs. Low-risk for adverse outcomes should lead to early hospital discharge or full treatment at home. Validated prognostic tools (i.e., clinical prognostic scoring systems, imaging studies, and cardiac laboratory biomarkers) assist with risk classification of patients who have acute symptomatic PE., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Current guidelines recommend low-molecular-weight-heparins (LMWH) monotherapy for 3 to 6 months as first-line treatment for cancer-associated venous thromboembolism (VTE). In clinical practice, enoxaparin and nadroparin are common agents used. However, differences in therapy adherence between these LMWHs have never been reported. Therefore, our aim was to compare adherence to enoxaparin and nadroparin in patients with cancer-associated VTE. Consecutive patients with active cancer and objectively confirmed VTE, treated at a Dutch or a Spanish hospital, were followed during LMWH therapy with a maximum of 180 days. Cumulative incidences of discontinuation of both LMWHs were estimated and compared according to the Kaplan-Meier method, applying a competing risk analysis to correct for mortality. A total of 366 patients were analyzed during LMWH treatment, of whom 284 patients (78%) were treated with enoxaparin and 82 (22%) with nadroparin. The cumulative incidence of discontinuation of enoxaparin and nadroparin treatment because of side effects was 30% (95% confidence interval [CI] 24-36) and 8.8% (95% CI 1.1-15), respectively. Competing risk analysis revealed a higher number of patients discontinuing enoxaparin due to side effects (adjusted hazard ratio [HR]: 2.8; 95% CI 1.06-7.2). Pain at the injection site was the most common reason of discontinuation in patients using enoxaparin, occurring in 32 patients, while it occurred in 1 patient using nadroparin (adjusted HR: 4.0; 95% CI 0.52-31). This analysis reveals that enoxaparin was associated with a higher risk of discontinuation because of side effects compared to nadroparin. However, given the nature of the patient groups, these findings should be followed by future studies., (Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Background: The inflammatory response associated with acute pulmonary embolism (PE) contributes to the development of right ventricular (RV) dysfunction. Nonsteroidal anti-inflammatory drugs (NSAIDs) may facilitate the reversal of PE-associated RV dysfunction., Methods: We randomly assigned normotensive patients who had acute PE associated with echocardiographic RV dysfunction and normal systemic blood pressure to receive intravenous (IV) diclofenac (two doses of 75mg in the first 24h after diagnosis) or IV placebo. All patients received standard anticoagulation with subcutaneous low-molecular-weight heparin (LMWH) and an oral vitamin K antagonist. RV dysfunction was defined by the presence of, at least, two of the following criteria: i) RV diastolic diameter>30mm in the parasternal window; ii) RV diameter>left ventricle diameter in the apical or subcostal space; iii) RV free wall hypokinesis; and iv) estimated pulmonary artery systolic pressure>30mmHg. Persistence of RV dysfunction at 48h and 7days after randomization were the primary and secondary efficacy outcomes, respectively. The primary safety outcome was major bleeding within 7days after randomization., Results: Of the 34 patients randomly assigned to diclofenac or placebo, the intention-to-treat analysis showed persistent RV dysfunction at 48h in 59% (95% confidence interval [CI], 33-82%) of the diclofenac group and in 76% (95% CI, 50-93%) of the placebo group (difference in risk [diclofenac minus standard anticoagulation], -17 percentage points; 95% CI, -47 to 17). Similar proportions (35%) of patients in the diclofenac and placebo groups had persistent RV dysfunction at 7days. Major bleeding occurred in none of patients in the diclofenac group and in 5.9% (95% CI, 0.2-29%) of patient in the placebo group., Conclusions: Due to slow recruitment, our study is inconclusive as to a potential benefit of diclofenac over placebo to reverse RV dysfunction in normotensive patients with acute PE., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01590342., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In normotensive patients with acute symptomatic pulmonary embolism (PE), the effect of undiagnosed obstructive sleep apnea (OSA) on cardiovascular (CV) outcomes lacks clarity. The Prognostic Significance of Obstructive Sleep Apnea in Patients With Acute Symptomatic Pulmonary Embolism (POPE) study is a multicenter, observational study designed to prospectively assess the prognostic significance of concomitant OSA in hemodynamically stable outpatients with acute symptomatic PE. Adult patients with acute stable PE are eligible. Recruited patients undergo an overnight sleep study using a level III portable diagnostic device within 7 days (and preferably within 48 hours) of diagnosis of PE. The sleep tracings are analyzed by a certified sleep technologist and audited by a sleep physician, both of whom are blinded to other study data. The patients are divided into 2 groups based on apnea-hypopnea index (AHI): OSA (AHI ≥15) and non-OSA (AHI <15) groups. The study uses a composite of PE-related death, CV death, clinical deterioration requiring an escalation of treatment, or nonfatal CV events (recurrent venous thromboembolism, acute myocardial infarction, or stroke) within 30 days after the diagnosis of PE as the primary outcome. The projected sample size of 225 patients will provide 80% power to test the hypothesis that OSA will increase the primary outcome from 7% in the non-OSA group to 20% in the OSA group, with α ≤0.05. The trial results will be important to understand the burden and CV effects of OSA in PE patients., (© 2017 Wiley Periodicals, Inc.)

Background: We sought to examine sex-related differences in the characteristics and outcome in patients presenting with acute symptomatic pulmonary embolism (PE)., Methods: We conducted a retrospective cohort study of 2,096 patients diagnosed with acute PE. The characteristics were recorded at presentation. Treatment was at the discretion of patients' physicians. The primary study outcome, all-cause mortality, and the secondary outcomes of PE-specific mortality, recurrent venous thromboembolism, and major bleeding were assessed during the first month of follow-up after PE diagnosis., Results: Overall, the women were older than the men and had significantly higher rates of immobilization. They had significantly lower rates of chronic obstructive pulmonary disease and cancer. Women had a higher prevalence of syncope and elevated brain natriuretic peptide levels. Thirty-day all-cause mortality was similar between women and men (7.1% versus 6.2%; P = 0.38). Male gender was not independently significantly associated with PE-related death (adjusted odds ratio [OR] 1.02; 95% CI, 0.50 to 2.07; P = 0.96). Restricting the analyses to haemodynamically stable patients (n = 2,021), female gender was an independent predictor of all-cause (adjusted OR 1.56; 95% CI, 1.07 to 2.28; P = 0.02) and PE-specific mortality (adjusted OR 1.85; 95% CI, 1.02 to 3.33; P = 0.04). Compared with men, women were 2.05 times more likely to experience a major bleed., Conclusions: Women and men with PE had different clinical characteristics, presentation, and outcomes. Women receiving anticoagulation have a significantly higher risk of major bleeding, suggesting the need for careful monitoring of anticoagulant intensity in women.

Objective: Clinical presentation and short-term prognosis of patients with travel-associated acute pulmonary embolism (PE) (i.e., economy class syndrome [ECS]) is not well understood., Methods: In this retrospective cohort study of patients with acute PE identified from a single center registry, we assessed the clinical presentation and the association between ECS and the outcomes of all-cause mortality, PE-related mortality, nonfatal venous thromboembolism and nonfatal major bleeding rates through 30days after initiation of PE treatment., Results: Of the 2,333 patients with acute symptomatic PE, 124 (5.3%; 95% confidence interval, 4.4-6.3%) had ECS. Patients with ECS were younger and had fewer comorbid diseases (recent bleeding, chronic obstructive pulmonary disease, congestive heart failure), but they presented with more signs of clinical severity (syncope [48% vs. 14%; P<.001], tachycardia [37% vs. 21%; P<.001], right ventricular dysfunction [31% vs. 19%; P<.01] and myocardial injury [57% vs. 28%; P<.001]) compared to those without ECS. Regression analyses showed a significantly lower risk of all-cause mortality for patients with ECS compared to patients without ECS (1.6% vs. 9.6%; P<.01). We did not detect a difference in PE-related mortality at 30days between those with and those without ECS (0.8% vs. 3.1%; P=.18)., Conclusions: PE patients with ECS are younger and have fewer comorbid diseases compared to those without ECS. Though they present with more signs of clinical severity, their short-term prognosis is excellent., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Rapid and accurate risk stratification is critical in determining the optimal treatment strategy for patients with acute pulmonary embolism (PE). Early identification of patients with normal blood pressure and a favorable prognosis ( low-risk PE ) might select a subset of patients for outpatient treatment, which is associated with reduced cost and improved patient satisfaction, and has been shown to be effective and safe. Alternatively, identification of normotensive patients deemed as having a high risk for PE-related adverse clinical events ( intermediate-high-risk PE ) might select a subset of patients for close observation and consideration of escalation of therapy. Clinical prognostic scores have been gaining importance in the classification of patients into these categories. They should be derived and validated following strict methodological standards, and their use in clinical practice should be encouraged., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The optimal approach to assess right ventricular (RV) function in patients with acute symptomatic pulmonary embolism (PE) lacks clarity., Methods: This study aimed to evaluate the optimal approach to assess RV function in normotensive patients with acute symptomatic PE. Outcomes assessed through 30-days after the diagnosis of PE included all-cause mortality and complicated course., Results: Eight hundred forty-eight patients were enrolled. Multidetector computed tomography (MDCT) and transthoracic echocardiography agreed on the presence or absence of RV overload in 449 (53%) patients. The combination of the simplified Pulmonary Embolism Severity Index (sPESI) and MDCT showed a negative predictive value for 30-day all-cause mortality of 100%. Of the 43% that had an sPESI of >0 points and MDCT RV enlargement, 41 (11.3%) experienced a complicated course that included 24 (6.6%) deaths. One hundred twenty-nine patients (15%) had an sPESI of >0 points, MDCT, and echocardiographic RV overload. Of these, 21 (16.3%) experienced a complicated course within the first 30days, and 10 (7.7%) of them died., Conclusions: Incorporation of echocardiographic RV overload to the sPESI and MDCT did not improve identification of low-risk PE patients, whereas it improved identification of those at intermediate-high risk for short-term complications., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: For patients diagnosed with acute pulmonary embolism (PE), the prognostic significance of concomitant right heart thrombi (RHT) lacks clarity., Methods: We performed a meta-analysis of studies that enrolled patients with acute PE to assess the prognostic value of echocardiography-detectable RHT for the primary outcome of short-term all-cause mortality and the secondary outcome of short-term PE-related mortality. Unrestricted searches were conducted of PubMed and Embase from 1980 through January 31, 2016, and used the terms "right heart thrombi," "pulmonary embolism," and "prognos.*" A random effects model was used to pool study results; Begg rank correlation method was used to evaluate for publication bias; and I 2 testing was used to assess for heterogeneity., Results: Six of 79 potentially relevant studies met the inclusion criteria (15,220 patients). Overall, 99 of 593 patients with echocardiography-detectable RHT died (16.7% [95% CI, 13.8-19.9]) compared with 639 of 14,627 without RHT (4.4% [95% CI, 4.0-4.7]). RHT had a significant association with short-term all-cause mortality in all patients (OR, 3.0 [95% CI, 2.2 to 4.1]; I 2  = 20%) and with PE-related death (three cohorts, 12,955 patients; OR: 4.8 [95% CI, 2.0-11.3; I 2  = 76%). Results were consistent for the prospective (two cohorts, 514 patients; OR, 4.8 [95% CI, 1.7-13.6]; I 2  = 56%) and the retrospective (four cohorts, 14,706 patients; OR, 2.8 [95% CI, 2.1 to 3.8]; I 2  = 0%) studies., Conclusions: In patients diagnosed with acute PE, concomitant RHT were significantly associated with an increased risk of death within 30 days of PE diagnosis., Trial Registry: PROSPERO registry; No.: CRD42016033960; URL: https://www.crd.york.ac.uk/prospero/., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Essentials Low-molecular-weight heparin (LMWH) injections for venous thromboembolism (VTE) may be burdensome. Patients with active cancer and confirmed VTE were included to evaluate LMWH continuation. The cumulative incidence of discontinuation was 21% after a median period of 90 days. One out of five patients discontinued LMWH injections because of side effects., Summary: Background Current guidelines recommend low-molecular-weight heparin (LMWH) monotherapy for 3-6 months as the first-line treatment for cancer-associated venous thromboembolism (VTE). However, although daily administration of LMWH injections over a course of several months may be burdensome, the number of patients who stop treatment because of LMWH side-effects is unknown. Objectives To evaluate the continuation rate and complications of daily LMWH injections in patients with cancer-associated VTE. Methods Consecutive patients with active cancer and objectively confirmed symptomatic proximal deep vein thrombosis and/or pulmonary embolism, treated at three Dutch hospitals and one Spanish hospital, were included to evaluate continuation LMWH therapy during LMWH treatment. Patients were excluded when they received other anticoagulants, were lost to follow-up, or experienced a venous catheter-associated thrombosis. Results A total of 372 patients were analyzed during LMWH treatment for a maximum of 180 days. The cumulative incidence of discontinuation was 21% (95% confidence interval [CI] 17-25) after a median period of 90 days (interquartile range 60-120 days). Only female sex was found to be significantly associated with premature LMWH discontinuation (odds ratio 1.6; 95% CI 1.03-2.5). Thirty patients (8.1%) developed recurrent VTE, 30 patients (8.3%) suffered a major bleed, and 106 patients (28%) died. Conclusion Our study reveals that one of five patients with cancer-associated VTE stopped LMWH injections because of side-effects. This finding provides relevant background information for current clinical trials investigating the efficacy and safety of direct oral anticoagulants as compared with LMWH., (© 2016 International Society on Thrombosis and Haemostasis.)

There is a lack of comprehensive data on the prevalence, predictors and prognostic significance of right heart thrombi (RHT) in pulmonary embolism.In this study of patients with pulmonary embolism from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry, we assessed the prevalence and predictors of RHT, and the association between the presence of RHT and the outcomes of all-cause mortality, pulmonary embolism-related mortality, recurrences, and major bleeding through 30 days after initiation of pulmonary embolism treatment.Of 12 441 patients with pulmonary embolism and baseline echocardiographic data, 2.6% had RHT. The following increased the risk of RHT: younger age, previous bleeding, congestive heart failure, cancer, syncope, systolic blood pressure <100 mmHg, and arterial oxyhaemoglobin saturation <90%. Patients with RHT were significantly more likely to die from any cause (adjusted OR 2.50 (95% CI 1.62-3.84); p<0.001) and from pulmonary embolism (adjusted OR 4.29 (95% CI 2.45-7.48); p<0.001) during follow-up. RHT was associated with an increased risk of recurrence during follow-up (1.8% versus 0.7%; p=0.04). Major bleeding was similar in patients with and without RHT.In patients presenting with pulmonary embolism, RHT is relatively infrequent. Patients with RHT had a worse outcome when compared with those without RHT., (Copyright ©ERS 2016.)

Background: A comprehensive evaluation of temporal trends in the treatment of patients who have DVT may assist with identification of modifiable factors that contribute to short-term outcomes., Methods: We assessed temporal trends in length of hospital stay and use of pharmacological and interventional therapies among 26,695 adults with DVT enrolled in the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2014. We also examined temporal trends in risk-adjusted rates of all-cause, pulmonary embolism-related, and bleeding-related death to 30 days after diagnosis., Results: The mean length of hospital stay decreased from 9.0 days in 2001 to 2005 to 7.6 days in 2010 to 2014 (P < .01). For initial DVT treatment, the use of low-molecular-weight heparin decreased from 98% to 90% (P < .01). Direct oral anticoagulants use increased from 0.5% in 2010 to 13.4% in 2014 (P < .001). Risk-adjusted rates of 30-day all-cause mortality decreased from 3.9% in 2001 to 2005 to 2.7% in 2010 to 2014 (adjusted rate ratio per year, 0.84; 95% CI, 0.74-0.96; P < .01). VTE-related mortality showed a nonstatistically significant downward trend (adjusted rate ratio per year, 0.70; 95% CI, 0.44-1.10; P = .13), whereas 30-day bleeding-related mortality significantly decreased from 0.5% in 2001 to 2005 to 0.1% in 2010-2014 (adjusted rate ratio per year, 0.55; 95% CI, 0.40-0.77; P < .01)., Conclusions: This international registry-based temporal analysis identified reductions in length of stay for adults hospitalized for DVT. The study also found a decreasing trend in adjusted rates of all-cause and bleeding-related mortality., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to compare the predictive value of two clinical prognostic models, the Spanish score and the simplified Pulmonary Embolism Severity Index (sPESI), in an independent cohort of patients diagnosed of acute symptomatic pulmonary embolism (PE)., Methods: We performed a retrospective analysis of a cohort composed of 1447patients with acute symptomatic PE. The Spanish score and the sPESI were calculated for each patient according to different clinical variables. We assessed the predictive accuracy of these scores for 30-day mortality, and a composite of non fatal recurrent venous thromboembolism and non fatal major bleeding, using Cstatistic, which was obtained by means of logistic regression and ROC curves., Results: Overall, 138 patients died (9.5%) during the first month of follow-up. Both scores showed an excellent predictive value for 30-day all-cause mortality (Cstatistic, 0.72 and 0.74), but the performance was poor for the secondary endpoint (Cstatistic, 0.60 and 0.59). The sPESI classified fewer patients as low risk (32% versus 62%; P<.001). Low-risk patients based on the sPESI had a lower 30-day mortality than those based on the Spanish score (1.1% versus 4.2%), while the 30-day rate of non fatal recurrent VTE or major bleeding was similar (2.2% versus 2.3%)., Conclusions: Both scores provide excellent information to stratify the risk of mortality in patients treated of PE. The usefulness of these models for nonfatal adverse events is questionable. The sPESI identified low-risk patients with PE better than the Spanish score., (Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.)

In recent years, both scientific and judicial sources have highlighted the need for more knowledge about minutiae variability, in order to improve their statistical application to fingerprint identification. In line with this trend toward improving our knowledge of this subject, the aim of the present study was to calculate the frequency with which 20 types of minutiae appeared in 2780 fingerprint impressions obtained from 278 individuals from two Argentinian population samples (100 individuals from Ramal and 178 from Puna-Quebrada). The different types of minutiae were located, identified, and quantified visually in two areas on the fingerprint, the inside and outside of a circle, the radius of which cut fifteen ridges perpendicularly, starting from the center cut of the axes defining the sectors. The non-equiprobability found in both population samples for the different minutiae types studied demonstrated that the evidential weight provided by these characteristics is not the same when applied in identification processes, whether used quantitatively (numerical standard) or qualitatively (holistic method). The results obtained for both populations were compared statistically with those published previously for a Spanish population sample, which had been collected using the same methodology. This comparison has enabled us to demonstrate, for the first time, the existence of significant differences between populations in minutiae frequencies, independently from the main pattern type., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: fewer than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV) therapy., Aims: thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells., Methods: we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC) patients, who had failed to respond to the (Peg-IFN/RBV), with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study)., Results: none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy., Conclusions: thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients.