Search

Elena Arellano-Orden,1,2 Carmen Calero,1,2 Cecilia López-Ramírez,1,2 Verónica Sánchez-López,1,2 José Luis López-Villalobos,1,2 María Abad Arranz,1,2 Ana Blanco-Orozco,1 Remedios Otero-Candelera,1,2 José Luis López-Campos1,21Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Seville, Spain; 2CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, SpainBackground: Previous studies have shown that the arterial wall is a potential source of inflammatory markers in COPD. Here, we sought to compare the expression of acute phase reactants (APRs) in COPD patients and controls both at the local (pulmonary arteries and lung parenchyma) and systemic (peripheral blood leukocytes and plasma) compartments.Methods: Consecutive patients undergoing elective surgery for suspected primary lung cancer were eligible for the study. Patients were categorized either as COPD or control group based on the spirometry results. Pulmonary arteries and lung parenchyma sections, peripheral blood leukocytes, and plasma samples were obtained from all participants. Gene expression levels of C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2, and SAA4) were evaluated in tissue samples and peripheral blood leukocytes by reverse transciption-PCR. Plasma CRP and SAA protein levels were measured by enzyme-linked immunosorbent assays. Proteins were evaluated in paraffin-embedded lung tissues by immunohistochemistry.Results: A total of 40 patients with COPD and 62 controls were enrolled. We did not find significant differences in the gene expression between COPD and control group. Both CRP and SAA were overexpressed in the lung parenchyma compared with pulmonary arteries and peripheral blood leukocytes. The expression of SAA was significantly higher in the lung parenchyma than in the pulmonary artery (2-fold higher for SAA1 and SAA4, P=0.015 and P

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. [ABSTRACT FROM AUTHOR]

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. [ABSTRACT FROM AUTHOR]

Background: Risk of VTE recurrence (VTEr) in patients with cancer-associated thrombosis (CAT) is high. Cancer-related risk factors for VTEr have been studied, but information about the importance of location of metastasis is scarce., Objectives: 1) Evaluate rate of VTEr in CAT patients according to location of metastasis, and 2) Identify variables associated to VTEr during long-term follow-up., Methods: A retrospective, single-center, non-interventional study of consecutives patients with CAT conducted between 2007 and 2022. Haematological neoplasms were excluded., Results: Among 1248 patients with CAT (age 64.1 ± 12.8 years; 48.2 % female) followed-up for 13.19 months (p25-75, 5.6-26.9) there were 141 VTEr. The rate of VTE recurrence in patients without and with metastasis were 4.72 per 100 patient-years (95%CI: 3.66-6) and 10.05 per 100 patient-years (95 % CI: 7.89-12.61), respectively. The metastases locations associated with VTEr, compared to those without metastasis, were lung (rate ratio [RR]: 2.21; 95 % CI: 1.42-3.43), liver (RR: 2.02; 95%CI: 1.26-3.24), pancreas (RR: 6.21; 95 % CI: 1.52-25.35), pleura (RR: 2.93; 95%CI: 1.58-5.41), bone (RR: 2.16; 95 % CI: 1.29-3.64) and adrenal (RR: 6.18; 95%CI: 2.97-12.86). Multivariate analysis of variables associated with VTEr beyond 12 months were male sex (hazard ratio [HR] 1.54, 95%CI: 1.08-2.19), ECOG performance status >1 (HR 1.74, 95%CI: 1.03-2.94), metastasis in 1-2 locations (HR 2.38, 95%CI: 1.68-3.37) and metastasis in >2 locations (HR 3.88, 95%CI: 1.68-8.98)., Conclusions: The rate of VTEr differs according to the location of metastasis. We identified variables related to VTEr during long-term follow-up which may help clinicians decide whether to continue anticoagulation., Competing Interests: Declaration of competing interest Dr. Jara-Palomares received grants from Leo Pharma and MSD, and personal fees from Daichii, Rovi, GlaxoSmithKline, and Actellion outside the submitted work. Dr. Carrier has received research funding from BMS, Pfizer, and Leo Pharma, and honoraria from Bayer, Pfizer, BMS, Servier, and Leo Pharma. No other conflicts of interest are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Pulmonary hypertension (PH) is a chronic and complex condition, requiring consistent management and education. The widespread use of smartphones has opened possibilities for mobile health apps to support both patients and health care professionals in monitoring and managing PH more effectively., Objective: This study aimed to identify and assess the quality of free smartphone apps for PH targeted at either patients or health care professionals., Methods: A systematic search was conducted on freely available apps for patients with PH and health care professionals, accessed from a Spanish IP address, on Android (Google Play) and iOS (App Store) platforms. Searches were performed in October 2022 and 2023. Apps were independently analyzed by two reviewers, focusing on general characteristics. Quality assessment was based on the Mobile Application Rating Scale (MARS) framework, and Mann-Whitney U tests compared mean MARS scores against specific variables., Results: In the overall study, 21 apps were identified. In the 2022 search, 19 apps were listed (9 iOS, 7 Android, 3 available on both platforms). In the subsequent 2023 search, 16 apps were identified (6 Android, 7 iOS, 3 available on both platforms). Of those identified in 2022, 14 remained available in 2023, with only 7 updated since 2022. In addition, 12 apps targeted patients or the general population, while 9 targeted health care professionals; none involved patients in the development or design. Conversely, 13 apps involving health care professionals were identified. There were 10 apps that received pharmaceutical industry funding. The primary goal for 81% (17/21) of the apps was to disseminate general information about PH. The overall mean MARS quality was acceptable in 2022 and 2023, with mean ratings of 3.1 (SD 0.6) and 3.3 (SD 0.5), respectively. The functionality category achieved the highest scores in both years, indicating ease of use and intuitive navigation. In contrast, the subjective quality domain consistently received the lowest ratings in the MARS assessment across both years. None of the apps underwent clinical testing themselves; however, 2 incorporated tools or algorithms derived from trials. The overall quality of iOS apps statistically outperformed that of Android apps in both years (P<.05). Furthermore, the involvement of health care professionals in app development was associated with enhanced quality, a trend observed in both years (P=.003 for both years)., Conclusions: This review of mobile health apps for PH reveals their emergent development stage, with generally acceptable quality but lacking refinement. It highlights the critical role of health care professionals in app development, as they contribute significantly to quality and reliability. Despite this, a notable stagnation in app quality and functionality improvement over 2 years points to a need for continuous innovation and clinical validation for effective clinical integration. This research advocates for future app developers to actively engage with health care professionals, integrate patient insights, and mandate rigorous clinical validation for PH management., (© Nerea Báez Gutiérrez, Héctor Rodríguez Ramallo, Elva María Mendoza-Zambrano, Berenice Brown Arreola, Bernardo Santos Ramos, Laila Abdel-kader Martín, Remedios Otero Candelera. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Background: Patients with cancer-associated thrombosis (CAT) face a heightened risk of clinically relevant bleeding (CRB). However, the relationship between these risks and the location of metastasis remains unclear., Methods: A single-center, non-interventional study of consecutive patients was conducted between 2007 and 2022, involving patients with CAT (n = 1,277). Our primary objectives were: 1) To estimate the rate of CRB based on metastasis location. 2) To assess the long-term risk of CRB., Results: Over a median follow-up of 14.2 months, 144 CRB were observed. The most frequent cancers were colon (19.2 %), lung (16.1 %), and breast (12.4 %). Fifty-two per-cent had metastases. Compared to patients without metastases, metastasis locations associated with CRB were lung metastases (rate 10.0 per 100 patients/year; 95 % confidence interval [CI] 6.6 to 14.6; risk ratio [RR]: 2; 95 % CI: 1.3-3.1), liver metastases (rate 10.1 per 100 patients/year; 95 % CI 6.5-14.9; RR: 2.0; 95 % CI: 1.3-3.2) and adenopathy metastases (rate 11.9 per 100 patients/year; 95 % CI 6.8-19.3; RR: 2.4; 95 % CI: 1.4-4.1). Multivariate analysis of variables associated to CRB at long term follow-up included ECOG > 1 (HR 3.0, 95 % CI 1.7-5.3), bladder cancer (HR 2.5, 95 % CI 1.3-4.8), prostate cancer (HR 2.2, 95 % CI 1.1-4.8) and lung metastases (HR 2.1, 95 % CI 1.3-3.6)., Conclusions: The bleeding rate seem differ depending on the location of metastasis. Additionally, lung metastasis was found to be associated with a long-term risk of CRB. These findings may justify the use of low dose of anticoagulation, although clinical trials need to demonstrate the efficacy and safety of this strategy., Competing Interests: Declaration of competing interest Dr. Jara-Palomares received grants from Leo Pharma, ROVI and MSD, and personal fees from Daichii, Rovi, and Johnson and Johnson outside the submitted work. No other conflicts of interest are declared., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background : The role of residual venous thrombosis (RVT) as a risk factor for recurrent venous thromboembolism (VTE) in patients with cancer-associated thrombosis (CAT) remains controversial. Methods : We conducted a cohort study on consecutive patients with CAT treated with tinzaparin recruited between 2007 and 2022. Primary outcome: RVT. Secondary outcomes: identification of variables associated with RVT and the role of RVT in VTE recurrences or clinically relevant bleeding (CRB). Results : Among 511 patients with CAT (age 64.1 years ± 13.4 years; 53.5% males) followed for 17.6 months (p25-75: 7.9-34), 35.8% (n = 183) presented RVT (at 6 months, 55.5%). Variables identified as being associated with RVT were ECOG performance status > 1, metastasis, and cancer location. Within 5 years, there were 57 CRB (11.2%; 95% CI: 8.6-14.2) and 67 VTE recurrences (13.1%, 95%CI: 10.3-16.4). Competing risk analysis identified that RVT at 6 months was associated with VTE recurrence within 5 years (sub-hazard ratio: 2.1; 95% CI: 1.2-3.7; p = 0.006), but not with CRB. Multivariate analysis confirmed that RVT at 6 months (HR: 2.1; 95% CI: 1.2-3.7) and metastases (HR: 1.7; 95% CI: 1.1-2.9) were associated with VTE recurrence within 5 years. Conclusions : RVT is high in patients with CAT. The presence of RVT at 6 months was associated with an increased risk of recurrent VTE over 5 years.

Objectives: Detecting occult cancer in patients with unprovoked venous thromboembolism (VTE) remains a significant challenge. Our objective was to investigate the potential predictive role of coagulation-related biomarkers in the diagnosis of occult malignancies., Methods: We conducted a nested case-control study with a 1-year prospective cohort of 214 patients with unprovoked VTE, with a focus on identifying occult cancer. At the time of VTE diagnosis, we measured various biomarkers, including soluble P-selectin (sP-selectin), dimerized plasmin fragment D (D-dimer), platelets, leukocytes, hemoglobin, total extracellular vesicles (EVs), EVs expressing tissue factor on their surface (TF+EVs), and EVs expressing P-selectin on their surface (Psel+EVs) in all participants., Results: We observed statistically significant increased levels of sP-selectin (P = .015) in patients with occult cancer. Despite an increase in Psel+EVs, TF+EVs, D-dimer, and platelets within this group, however, no significant differences were found. When sP-selectin exceeded 62 ng/mL and D-dimer surpassed 10,000 µg/L, the diagnosis of occult cancer demonstrated a specificity of up to 91% (95% CI, 79.9%-96.7%)., Conclusions: The combination of sP-selectin and D-dimer can be a valuable biomarker in detecting occult cancer in patients with unprovoked VTE. Further research is necessary to ascertain whether easily measurable biomarkers such as sP-selectin and D-dimer can effectively distinguish between patients who have VTE with and without hidden malignancies., (© American Society for Clinical Pathology, 2024.)

Background: The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain., Research Question: Does supplemental oxygen improve echocardiographic parameters in nonhypoxemic patients with intermediate-risk PE?, Study Design and Methods: This pilot trial randomly assigned nonhypoxemic patients with stable PE and echocardiographic right ventricle (RV) enlargement to receive anticoagulation plus supplemental oxygen for the first 48 h vs anticoagulation alone. The primary outcome was normal echocardiographic RV size 48 h after randomization. Secondary efficacy outcomes were the numerical change in the RV to left ventricle (LV) diameter ratio measured 48 h and 7 days after randomization with respect to the baseline ratio measured at inclusion., Results: The study was stopped prematurely because of the COVID-19 pandemic after recruiting 70 patients (mean ± SD age, 67.3 ± 16.1 years; 36 female [51.4%]) with primary outcome data. Forty-eight h after randomization, normalization of the RV size occurred in 14 of the 33 patients (42.4%) assigned to oxygen and in eight of the 37 patients (21.6%) assigned to ambient air (P = .08). In the oxygen group, the mean RV to LV ratio was reduced from 1.28 ± 0.28 at baseline to 1.01 ± 0.16 at 48 h (P < .001); in the ambient air group, mean RV to LV ratios were 1.21 ± 0.18 at baseline and 1.08 ± 0.19 at 48 h (P < .01). At 90 days, one major bleeding event and one death (both in the ambient air group) had occurred., Interpretation: In analyses limited by a small number of enrollees, compared with ambient air, supplemental oxygen did not significantly increase the proportion of patients with nonhypoxemic intermediate-risk PE whose RV to LV ratio normalized after 48 h of treatment. This pilot trial showed improvement in some ancillary efficacy outcomes and provides support for a definitive clinical outcomes trial., Trial Registry: ClinicalTrials.gov; No.: NCT04003116; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: L. J.-P. reports personal fees from Bayer Hispania, Actelion, Rovi, Pfizer, Menarini, and Leo Pharma, outside the submitted work. R. O.-C. has served as an advisor or consultant for Leo Pharma, Actelion, Bayer Hispania, and Sanofi; as a speaker or a member of a speakers’ bureau for Leo Pharma, Sanofi, and Rovi; and has received grants for clinical research from Leo Pharma and Bayer Hispania. P. R.-A. has served as an advisor or consultant for Leo Pharma, Pfizer, and Viatris; has served as a speaker or a member of a speakers’ bureau for Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, ROVI, and Viatris; and has received grants for clinical research from ROVI. M. M. has served as an advisor or consultant for Leo Pharma and Sanofi; has served as a speaker or a member of a speakers’ bureau for Bristol-Myers Squibb and Sanofi; and has received grants for clinical research from Sanofi and ROVI. B. B. 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. D. J. has served as an advisor or consultant for Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, Pfizer, ROVI, and Sanofi; has served as a speaker or a member of a speakers’ bureau for Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, ROVI, and Sanofi; and has received grants for clinical research from Daiichi Sankyo, Sanofi, and ROVI. None declared (D. B., D. D., C. R., J. M., A. R., J. L. L., R. L., L. C., A. M.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Randomized controlled trials (RCTs) that conduct subgroup analyses have the potential to provide information on treatment decisions in specific groups of patients from heterogeneous populations. Although we understand several factors can modify the incidence of venous thromboembolism (VTE) and the benefit/risk ratio of anticoagulation treatments, further evidence is warranted to show the heterogeneity of treatment effects in different subgroups of patients., Aims: The primary purpose was to evaluate the appropriateness and interpretation of subgroup analysis performed on VTE RCTs reporting pharmacological interventions., Materials and Methods: A systematic review of RCTs published between January 2017 and January 2022 was conducted. Claims of subgroup effects were evaluated with predefined criteria. High-quality claims of subgroup effect were further analyzed and discussed., Results: Overall, 28 RCTs with a generally low bias risk were included. The purposes of the treatments included pharmacologic thromboprophylaxis (17), therapeutic dose anticoagulation (9), and catheter-directed pharmacologic thrombolysis (2). The evaluated subgroup analyses generally presented: a high number of subgroup analyses reported, a lack of prespecification, and a lack of usage of statistical tests for interaction. The authors reported 13 claims of subgroup effect; only two were considered potentially reliable to represent heterogeneity in the direction or magnitude of treatment effect., Conclusions: Subgroup analyses of VTE RCTs reporting pharmacologic interventions are generally methodologically poor. Most claims of subgroup effect did not meet critical criteria and lacked credibility. Clinicians in this field may proceed with scepticism when assessing claims of subgroup effects due to methodological concerns and misleading interpretations., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Clinical practice guidelines recommend that patients with incidental venous thromboembolism (VTE) receive the same anticoagulant therapy as those with symptomatic VTE. We aimed to compare the rate of complications between cancer patients with incidental and symptomatic VTE through a long-term follow-up cohort., Methods: We performed a post hoc analysis of prospective studies of cancer patients with VTE between 2008 and 2019, with the primary outcome of rates of recurrent VTE and clinically relevant bleeding (CRB) in incidental and symptomatic VTE groups., Results: In total, 796 patients were included, of which 42.8% had incidental VTE. No significant differences were noted in the rate of recurrent VTE (0.4 per 100 patients/month vs. 0.5 per 100 patients/month; p  = 0.313) and in the rate of CRB (0.6 per 100 patients/month vs. 0.5 per 100 patients/month; p  = 0.128) between patients with incidental VTE and symptomatic VTE, respectively. At six-month follow-ups, the cumulative incidence of CRB was significantly higher in patients with incidental VTE than that in those with symptomatic VTE (7.9% vs. 4.4%, respectively; OR: 1.8; 95% CI: 1.01-3.2)., Conclusion: Cancer patients with incidental VTE had similar rates of CRB and VTE recurrence in long-term follow-up compared with patients with symptomatic VTE. At six-month follow-ups, patients with incidental VTE had a higher cumulative incidence of CRB than those with symptomatic VTE., Competing Interests: LJ-P: Grants from Leo Pharma and MSD and personal fees from Daichii, Rovi, GlaxoSmithKline, and Actellion outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Barca-Hernando, Lopez-Ruz, Marin-Romero, Elias-Hernandez, Otero-Candelera and Jara-Palomares.)

Introduction: There is currently no validated score capable of classifying cancer-associated pulmonary embolism (PE) in its full spectrum of severity. This study has validated the EPIPHANY Index, a new tool to predict serious complications in cancer patients with suspected or unsuspected PE., Method: The PERSEO Study prospectively recruited individuals with PE and active cancer or receiving antineoplastic therapy from 22 Spanish hospitals. The estimation of the relative frequency θ of complications based on the EPIPHANY Index categories was made using the Bayesian alternative for the binomial test., Results: A total of 900 patients, who were diagnosed with PE between October 2017 and January 2020, were enrolled. The rate of serious complications at 15 days was 11.8%, 95% highest density interval [HDI], 9.8-14.1%. Of the EPIPHANY low-risk patients, 2.4% (95% HDI, 0.8-4.6%) had serious complications, as did 5.5% (95% HDI, 2.9-8.7%) of the moderate-risk participants and 21.0% (95% HDI, 17.0-24.0%) of those with high-risk episodes. The EPIPHANY Index was associated with overall survival (OS) in patients with different risk levels: median OS was 16.5, 14.4, and 4.4 months for those at low, intermediate, and high risk, respectively. Both the EPIPHANY Index and the Hestia criteria exhibited greater negative predictive value and a lower negative likelihood ratio than the remaining models. The incidence of bleeding at 6 months was 6.2% (95% HDI, 2.9-9.5%) in low/moderate-risk vs 12.7% (95% HDI, 10.1-15.4%) in high-risk (p-value = 0.037) episodes. Of the outpatients, serious complications at 15 days were recorded in 2.1% (95% HDI, 0.7-4.0%) of the cases with EPIPHANY low/intermediate-risk vs 5.3% (95% HDI, 1.7-11.8%) in high-risk cases., Conclusion: We have validated the EPIPHANY Index in patients with incidental or symptomatic cancer-related PE. This model can contribute to standardize decision-making in a scenario lacking quality evidence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sánchez-Cánovas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The clinical characteristics and outcomes of cancer patients with lower-limb isolated superficial vein thrombosis (SVT) have not been consistently evaluated., Methods: We used data in the RIETE registry to compare the clinical characteristics and 90-day outcomes for patients with: (1) active cancer and lower-limb SVT; (2) active cancer and lower-limb deep vein thrombosis (DVT); (3) lower-limb SVT without cancer. The primary outcomes included subsequent symptomatic SVT, DVT or pulmonary embolism (PE). Secondary outcomes were major bleeding and death., Results: From March 2015 to April 2021, there were 110 patients with cancer and SVT, 1695 with cancer and DVT, and 1030 with SVT but no cancer. Most patients in all subgroups (93%, 99% and 96%, respectively) received anticoagulants, while those with SVT received lower daily doses of low-molecular-weight heparin (114 ± 58, 163 ± 44, and 106 ± 50 IU/kg, respectively). During the first 90 days, 101 patients (3.6%) developed subsequent VTE (PE 47, DVT 41, SVT 13), whereas 72 (2.5%) had major bleeding and 282 (9.9%) died. Among the three groups, 90-day events were, respectively: VTE at rates of 7.3%, 4.0% and 2.4%; major bleeding at rates of 2.7%, 3.9% and 0.3%; mortality at rates of 8.2%, 16% and 0.3%. Between D90 and D180, only one SVT recurrence and one death occurred in SVT cancer patients. In multivariable analysis, cancer was associated with subsequent VTE (HR = 2.04; 1.15-3.62), while initial presentation as SVT or DVT were not associated with a different risk., Conclusions: The risk for subsequent VTE (including symptomatic SVT, DVT or PE) was similar in cancer patients with isolated SVT than in those with isolated DVT.

Background: Clinical guidelines suggest continuing anticoagulation therapy for >6 months for patients with active cancer and venous thromboembolism (VTE). However, data regarding the safety of its discontinuation are scarce., Objectives: To valuate the risk factors and the incidence of recurrent VTE 6 months after the discontinuation of anticoagulation therapy in patients with cancer-associated thrombosis (CAT)., Methods: We performed a retrospective study on consecutive patients with CAT recruited between 2008 and 2019. The primary and secondary outcomes were recurrent VTE at 6 and 12 months, respectively. Sensitivity analyses were conducted to investigate the possible heterogeneity of these effects., Results: A total of 311 patients were included, among whom 33.4% had metastases and 30.8% were still receiving oncological treatment after 6 months of anticoagulant therapy. At 6 and 12 months, the incidences of recurrent VTE were 6.1% (95% CI, 3.5-9.4%) and 8.7% (95% CI, 5.8-12.4%), respectively. Recurrent VTE was more frequent in patients with metastases at 6 (sub-distribution hazard ratio [SHR] 3.83; 95% CI, 1.54-9.52) and 12 months (SHR 5; 95% CI, 2.2-11.5). Patients with incidental VTE had fewer recurrent events at 6 (SHR 0.3; 95% CI, 0.1-0.8) and 12 months (SHR 0.3; 95% CI, 0.1-0.6) after discontinuing the anticoagulant therapy., Conclusion: The incidence of recurrent VTE at 6 and 12 months following the discontinuation of anticoagulant therapy is higher in patients with CAT. Patients with metastases were at an increased risk of recurrent VTE, whereas patients with incidental VTE were at a lower risk., (© 2023 The Author(s).)

Background: Clinical guidelines indicate that in patients with cancer-associated thrombosis (CAT), anticoagulant treatment should be continued beyond 6 months as long as the cancer is active. We aimed to analyse the safety of low-molecular-weight heparin (LMWH) beyond 12 months in patients with CAT., Methods: We performed a post hoc analysis of consecutive CAT patients from October 2008 to December 2019. The primary outcome was the rate of clinically relevant bleeding (CRB), and we compared two periods (1-12 vs. 12-24 months). Hazard ratio (HR), competing risk analysis and sensitivity analyses were performed., Results: Of the 588 patients included, 30.1% (n = 177) received LMWH beyond 12 months. The rate of CRB in the first 12 months compared to the 12-24 month period was 3.2 per 100 patients/month (95% CI 2.5-4.1) vs. 0.9 per 100 patients/month (95% CI 0.4-1.5), (P < 0.0001). The competing risk analysis of CRB comparing both periods showed a lower sub-distribution hazard ratio (SHR) during the period 12-24 months (SHR: 0.5, 95% CI: 0.3-0.8, P < 0.001)., Conclusion: In patients with cancer-associated thrombosis under anticoagulant treatment with LMWH, the rate of clinically relevant bleeding and major bleeding were lower beyond 12 months., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Pulmonary hypertension (PH) treatment decisions are driven by the results of randomized controlled trials (RCTs). Subgroup analyses are often performed to assess whether the intervention effect will change due to the patient's characteristics, thus allowing for individualized decisions. This review aimed to evaluate the appropriateness and interpretation of subgroup analyses performed in PH-specific therapy RCTs published between 2000 and 2020. Claims of subgroup effects were evaluated with prespecified criteria. Overall, 30 RCTs were included. Subgroup analyses presented: a high number of subgroup analyses reported, lack of prespecification, and lack of interaction tests. The trial protocol was not available for most RCTs; significant differences were found in those articles that published the protocol. Authors reported 13 claims of subgroup effect, with 12 claims meeting four or fewer of Sun's criteria. Even when most RCTs were generally at low risk of bias and were published in high-impact journals, the credibility and general quality of subgroup analyses and subgroup claims were low due to methodological flaws. Clinicians should be skeptical of claims of subgroup effects and interpret subgroup analyses with caution, as due to their poor quality, these analyses may not serve as guidance for personalized care.

Background: Chronic obstructive pulmonary disease (COPD) is a condition resulting from a persistent inflammatory state in the airways even after smoking cessation. Intriguingly, the reasons behind this persistence of the inflammatory influx without smoking exposure have not been fully unraveled. We aimed to explore the hypothesis that systemic inflammation in COPD patients influences lung cell inflammatory response., Methods: We cultured human lung fibroblast and human airway epithelial cell lines with plasma from COPD patients (four emphysematous-COPD, four asthma-COPD overlap, four chronic bronchitis-COPD, and four bronchiectasis- COPD), and four smokers or ex-smokers without COPD as controls. Non-stimulated cells were used as controls. We measured Interleukine-8 (IL-8), C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) in plasma and culture supernatants by ELISA., Results: Cells stimulated with plasma from COPD patients and non-COPD smoker subjects produced higher CRP, IL- 8 and MMP-9 levels, an increase for COPD in CRP (p=0.029) in epithelial cells and IL-8 (p=0.039) in fibroblasts and decrease for MMP-9 (p=0.039) in fibroblasts, compared with non-stimulated cells. The response was higher in epithelial cells for IL-8 (p=0.003) and in fibroblasts for MMP-9 (p=0.063). The plasma from chronic bronchitis and bronchiectasis phenotypes induced higher IL-8 in fibroblasts., Conclusions: Plasma from COPD patients increases the inflammatory response in lung epithelial cells and lung fibroblasts, with a different response depending on the cell type and clinical phenotype., (©Copyright: the Author(s).)

On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Till now, it affected 452.4 million (Spain, 11.18 million) persons all over the world with a total of 6.04 million of deaths (Spain, 100,992). It is observed that 75% of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. It was shown that people with underlying chronic illnesses are more likely to get it and grow seriously ill. Individuals with COVID-19 who have a past medical history of cardiovascular disorder, cancer, obesity, chronic lung disease, diabetes, or neurological disease had the worst prognosis and are more likely to develop acute respiratory distress syndrome or pneumonia. COVID-19 can affect the respiratory system in a variety of ways and across a spectrum of levels of disease severity, depending on a person's immune system, age and comorbidities. Symptoms can range from mild, such as cough, shortness of breath and fever, to critical disease, including respiratory failure, shock and multi-organ system failure. So, COVID-19 infection can cause overall worsening of these previous respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, etc. This review aims to provide information on the impact of the COVID-19 disease on pre-existing lung comorbidities., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Over recent decades, a number of studies have revealed the possible role of different types of diets, as well as the nutritional elements they are made up of, in the pathogenesis of chronic obstructive pulmonary disease (COPD). To date, dietary factors have been identified to play a role in the prevention of COPD, with evidence from antioxidant nutrients, vitamins, and fiber intake. Additionally, certain dietary patterns such as the Mediterranean diet, together with other Western diets, provide evidence of the influence on COPD development, promoting lung health through nutritional approaches, and giving us an opportunity for intervention. The effect of diet on COPD is conveyed by 3 mechanisms: regulation of inflammation, oxidative stress, and carbon dioxide produced/oxygen intake. Current advances have begun to highlight the possible role of diet in modifying gene expression in certain individuals that predisposes them to COPD through epigenetic modifications. The relation between dietary intake and epigenetic factors has therefore outlined nutriepigenomics as a possible missing link in the relation between environmental exposure to smoke and the appearance of a subsequent chronic bronchial obstruction. This review summarizes the evidence regarding the influence of dietary patterns and nutrients and epigenetic regulatory mechanisms on COPD development and prevention with the aim of encouraging clinical research on the impact of dietary modifications on COPD-related clinical outcomes. This review highlights the importance of proposing and carrying out future studies focused on the modulating effects of certain nutrients on epigenetic changes in patients with specific COPD phenotypes (bronchiectasis, emphysema, asthma/COPD, chronic bronchitis), and their individual responses to cigarette smoking, environmental pollution, or other noxious particles. The objectives of these future studies must be directed to the development of novel therapeutic approaches and personalized management of COPD., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Anemia is a common condition in cancer patients and is associated with a wide variety of symptoms that impair quality of life (QoL). However, exactly how anemia affects QoL in cancer patients is unclear because of the inconsistencies in its definition in previous reports. We aimed to examine the clinical impact of anemia on the QoL of cancer patients using specific questionnaires. We performed a post-hoc analysis of a multicenter, prospective, case-control study. We included patients with cancer with (cases) or without (controls) anemia. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life questionnaire version 3.0 (EORTC QLQ-C30) and Euro QoL 5-dimension 3-level (EQ-5D-3L) questionnaire. Statistically significant and clinically relevant differences in the global health status were examined. From 2015 to 2018, 365 patients were included (90 cases and 275 controls). We found minimally important differences in global health status according to the EORTC QLQ-C30 questionnaire (case vs. controls: 45.6 vs. 58%, respectively; mean difference: -12.4, p < 0.001). Regarding symptoms, cancer patients with anemia had more pronounced symptoms in six out of nine scales in comparison with those without anemia. In conclusion, cancer patients with anemia had a worse QoL both clinically and statistically.

In symptomatic acute pulmonary embolism (PE), the presence of deep vein thrombosis (DVT) is a risk factor for 30- and 90-day mortality. In patients with cancer and incidental PE, the prognostic effect of concomitant incidental DVT is unknown. In this retrospective study, we examined the effect of incidental DVT on all-cause mortality in such patients. Adjusted Cox multivariate regression analysis was used for relevant covariates. From January 2010 to March 2018, we included 200 patients (mean age, 65.3 ± 12.4 years) who were followed up for 12.5 months (interquartile range 7.4-19.4 months). Of these patients, 62% had metastases, 31% had concomitant incidental DVT, and 40.1% ( n = 81) died during follow-up. All-cause mortality did not increase in patients with DVT (hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.43-2.75, p = 0.855). On multivariate analysis, weight (adjusted HR 0.96, 95% CI 0.92-0.99, p = 0.032), and metastasis (adjusted HR 10.26, 95% CI 2.35-44.9, p = 0.002) were predictors of all-cause mortality. In conclusion, low weight and presence of metastases were associated with all-cause mortality, while presence of concomitant DVT was unrelated to poorer survival.

Background: The aim was to analyze the temporal relationship between short-term air pollution exposure and acute symptomatic unprovoked pulmonary embolism (PE)., Patients/methods: We performed a prospective, multicenter study in consecutive patients diagnosed with acute symptomatic unprovoked PE from February 2012 to January 2013. We analyzed demographic and clinical data, patients' addresses, meteorological and air pollutants data (PM 10 , SO 2 , CO, NO 2 , ozone emission data). We considered the number of days the patient had symptoms, and the study period constituted the previous 30 days. Likewise, the mean annual data of the reference season were calculated as well as the data of the 30-day study period corresponding to the same dates in the previous 3 years in order to obtain the monthly mean of the different pollutants for each period., Results: A total of 162 patients with acute symptomatic PE were recruited (43.2% unprovoked PE). The air pollutants could be determined in 50% of the patients with unprovoked PE, and a final analysis was performed in 35 patients. In the multiple comparison analysis to verify a possible correlation between the study period and the annual median, only NO 2 showed a statistically significant association (p = 0.009). When comparing the study period with the previous 3 years, only NO 2 maintained a statistically significant association for the 3 study periods., Conclusions: We found a relationship between short-term exposure to NO 2 and the presence of unprovoked PE., Competing Interests: Declaration of competing interest LJP reports personal fees from Bayer Hispania, Actelion, Rovi, PFIZER, Menarini, and Leo-Pharma, outside the submitted work. RO reports Grant support from Leo-Pharma and Bayer HealthCare-Fees for serving on advisory boards and giving lectures from Leo-Pharma, Rovi, Bayer HealthCare, MSD and Actelion. There is no other conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Scales for predicting venous thromboembolism (VTE) recurrence are useful for deciding the duration of the anticoagulant treatment. Although there are several scales, the most appropriate for our setting has not been identified. For this reason, we aimed to validate the DASH prediction score and the Vienna nomogram at 12 months., Methods: This was a retrospective study of unselected consecutive VTE patients seen between 2006 and 2014. We compared the ability of the DASH score and the Vienna nomogram to predict recurrences of VTE. The validation was performed by stratifying patients as low-risk or high-risk, according to each scale (discrimination) and comparing the observed recurrence with the expected rate (calibration)., Results: Of 353 patients evaluated, 195 were analyzed, with an average age of 53.5 ± 19 years. There were 21 recurrences in 1 year (10.8%, 95% CI: 6.8%-16%). According to the DASH score, 42% were classified as low risk, and the rate of VTE recurrence in this group was 4.9% (95% CI: 1.3%-12%) vs. the high-risk group that was 15% (95% CI: 9%-23%) (p <.05). According to the Vienna nomogram, 30% were classified as low risk, and the rate of VTE recurrence in the low risk group vs. the high risk group was 4.2% (95% CI:0.5%-14%) vs. 16.2% (95% CI: 9.9%-24.4%) (p <.05)., Conclusions: Our study validates the DASH score and the Vienna nomogram in our population. The DASH prediction score may be the most advisable, both because of its simplicity and its ability to identify more low-risk patients than the Vienna nomogram (42% vs. 30%)., (Copyright © 2019 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Optimal duration of anticoagulation for cancer-associated thrombosis (CAT) remains unclear. This study assessed D-dimer (DD) and high-sensitivity C-reactive protein (hs-CRP) levels after the withdrawal of anticoagulation treatment to predict the risk of venous thromboembolism (VTE) recurrence among patients with CAT., Methods: Prospective, multicentre study to evaluate CAT with ≥3 months of anticoagulation that was subsequently discontinued. Blood samples were taken when patients stopped the anticoagulation and 21 days later to determine the DD and hs-CRP levels. All patients were followed up for 6 months to detect VTE recurrence., Results: Between 2013 and 2015, 325 patients were evaluated and 114 patients were ultimately enrolled in the study. The mean age was 62 ± 14 years and nearly 40% had metastasis. Ten patients developed VTE recurrence within 6 months (8.8%, 95% confidence interval [CI]: 4.3-15.5%). The DD and hs-CRP levels after 21 days were associated with VTE recurrence. The subdistribution hazard ratios were 9.82 for hs-CRP (95% CI: 19-52) and 5.81 for DD (95% CI: 1.1-31.7)., Conclusions: This study identified that hs-CRP and DD were potential biomarkers of VTE recurrence after discontinuation of anticoagulation in CAT. A risk-adapted strategy could identify low-risk patients who may benefit from discontinuation of anticoagulation.

Background: Survivin is a well-known member of the inhibitor of apoptosis family, and has been related to increased tumour aggressivity, both in tissue and in pleural fluid., Objectives: In patients with malignant pleural effusion, we sought to investigate the changes in pleural fluid survivin concentrations induced by talc instillation into the pleural space. Those changes were also examined in relation to pleurodesis outcome and patient survival., Methods: We investigated 84 patients with malignant pleural effusion who underwent talc pleurodesis. Of them, 32 had breast cancer, 25 lung cancer and 27 had mesothelioma. Serial samples of pleural fluid were obtained before thoracoscopy (baseline) and 24 hours thereafter., Results: Survivin levels were successfully quantified in all pleural fluid samples, and they were significantly higher in samples obtained after thoracoscopic talc poudrage compared with baseline (P < .001). Patients with higher pleural fluid survivin levels at baseline had a significantly poorer pleurodesis outcome (P = .004). A 30 pg/mL cut-off for baseline survivin in pleural fluid predicted failure of pleurodesis with a 54% sensitivity and 79% specificity (P = .009). Moreover, median postpleurodesis survival of patients with baseline survivin levels ≥30 pg/mL was 4 months (range: 0.1-38), compared with 13 months (range: 0.1-259) in patients below that cut-off (P < .001)., Conclusion: Elevated pleural fluid survivin concentrations are useful to predict failure of pleurodesis and are associated with shorter survival in patients with malignant pleural effusion., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)