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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 : 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.

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

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: 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: Respiratory health is closely related to immune system function, and diet can also influence immune homeostasis. Diet, an important part of a healthy lifestyle, is also linked to respiratory health. We aimed to explore the relationship between different dietary patterns and the risk of chronic respiratory diseases (CRDs), including chronic bronchitis (CB), emphysema, and asthma. Method: A total of 23,042 adults from the United States were selected from the National Health and Nutrition Examination Survey (NHANES) dataset between 2007 and 2018. Diet quality was assessed using 2-day, 24-hour dietary recall data and quantified as the Healthy Eating Index-2020 (HEI-2020), the Dietary Inflammation Index (DII), the Mediterranean Dietary Index (MEDI), and the Dietary Approaches to Stop Hypertension Index (DASHI). Binary logistic regression models, restricted cubic splines (RCS), and the weighted quartile sum (WQS) models were used to assess the relationship between diet quality and the risk of CB, emphysema, and asthma. Results: In logistic regression analyses of the four dietary indices with the three chronic respiratory diseases, it was consistently observed that higher dietary quality scores were linked to a reduced risk of respiratory disease. These consistent trends were also evident in the assessments of the dose–response relationship between dietary quality score and the risk of respiratory disease. Furthermore, evaluations of the combined effects of dietary components across different dietary indices in the risk of chronic respiratory disease yielded results consistent with the logistic regression models. Notably, high-quality protein, minerals, and fiber-rich fruits and vegetables emerged as the food groups making the most significant contributions to health across different dietary indices. Conclusion: Low-quality diets, lacking in high-quality protein, minerals, and fruits and vegetables rich in dietary fiber, are associated with a higher risk of chronic respiratory disease, regardless of the dietary index used to measure diet quality. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic represents a global health phenomenon that will sadly remain part of our history. It had innumerable consequences for society and people's lives. With different mechanisms, COVID-19 has been pointed out as a factor in the pathophysiology of several secondary disorders or the deterioration of pre-existing conditions. Migraine is a frequent disorder that can be influenced by several conditions, including psychologically stressful conditions or infectious diseases. The purpose of the present study is to gain insight into the influence of COVID-19 on the clinical characteristics of patients with migraine. A self-administrable questionnaire has been developed, asking for migraine features before and after COVID-19 infection. One hundred and two patients who had been infected at least once were included. After COVID-19 infection, 54 reported the worsening of migraine, 45 noticed no variation, and 3 reported an improvement. After the infection, 21 patients changed preventive therapy due to the loss of efficacy of the previous one. The most effective treatments in this subpopulation were gene-related peptide monoclonal antibodies. The presented data confirm that the influence of COVID-19 is heterogeneous in patients with migraine, but new treatments may be effective in controlling the symptoms among those who report a worsening of the disease. [ABSTRACT FROM AUTHOR]

We report the case of a 28-year-old woman taking contraceptives diagnosed with pulmonary embolism with a mass in the right atrium demonstrated by trans-thoracic echocardiogram that was not recognized on a previous angio-CT. Initially, it was thought to be a thrombus, but trans-oesophageal echocardiography and cardiac MRI showed data suggestive of cardiac neoplasm. Pericardial effusion and adjacent myocardial wall thickening noted on trans-oesophageal echocardiography were reported as signs that supported the possibility of malignancy, although cardiac MRI did not show wall infiltration signs. On the contrary, it demonstrated enhancement, which excludes the thrombotic nature of the mass and supports the diagnosis of neoplasm. The patient underwent surgery and biopsy proved that the mass was a myxoma. While myxomas are the most common among primary cardiac tumors, its attachment to the atrium free wall, far from the inter-atrium septum, the bi-lobed shape and accompanying pericardial effusion were atypical.

We report a rare case of synchronous unprovoked upper extremity deep vein thrombosis (UEDVT) and pulmonary emboli (PE) with subsequent chronic thromboembolic pulmonary hypertension (CTEPH). A 23-year-old woman presented with ongoing exertional dyspnoea despite anticoagulation for bilateral PE and unprovoked subclavian vein UEDVT 5 years ago. 5 Ferrer Galvan M, Jara Palomares L, Caballero Eraso C, Lopez Villalobos JL, Elias Hernandez T, Otero Candelera R. Chronic thromboembolic pulmonary hypertension due to upper-extremity deep vein thrombosis caused by thoracic outlet syndrome. [Extracted from the article]

Objective: To explore the relationship between dietary flavonoids and bronchitis, emphysema and asthma. Method: A total of 11743 United States adults were extracted from the National Health and Nutrition Examination Survey (NHANES) in 2007–2008, 2009–2010 and 2017–2018. Of these, 47.7% were male and 52.3% female. Dietary flavonoid intake assessed using FDNNS and 24-hour dietary recall data. Inclusion of demographics (gender, age, education, family income), behavioral factors (BMI, smoking, drinking status, diet), chronic disease information (diabetes, hypertension) as covariates to eliminate confounding. Stepwise logistic regression was used to analyze the association between total dietary flavonoid intake and the risk of chronic respiratory disease. Weighted quantile sum regression (WQS) was used to analyze the association between 29 dietary flavonoids and the risk of chronic respiratory disease. Restricted cubic spline was used to analyze the dose-response relationship between dietary flavonoid intake and risk of chronic respiratory disease. Results: Stepwise logistic regression results showed that higher flavonoid intake in men was associated with a lower risk of CB and asthma (OR of CB: 0.55(0.31–0.97); OR of asthma: 0.72(0.52–0.99)), and WQS results showed a mixed health effect for total flavonoids and chronic respiratory tract in response to the 29 flavonoid fractions (OR of asthma: 0.97(0.94–0.99); OR of emphysema: 0.95(0.90–0.99)). Glycitein had the highest health contribution of 26.2% for emphysema; Eriodictyol had the highest health contribution of 32.13% for asthma, respectively. The RCS showed a dose-response relationship between flavonoids and respiratory tract health. The maximum dose for ingesting flavonoids to gain respiratory health benefits is 1500 mg/d. Conclusion: Higher dietary flavonoid intake was associated with lower chronic respiratory risk in adult U.S. men. Also 29 dietary flavonoid components have an overall health effect on respiratory health. Glycitein and Eriodictyol may have potential health effects on the respiratory system. 1500 mg/day may be the Tolerable Upper Intake Level of dietary flavonoids for respiratory health in U.S. adults. [ABSTRACT FROM AUTHOR]

Of all the numerous nanosized extracellular vesicles released by a cell, the endosomal-originated exosomes are increasingly recognized as potential therapeutics, owing to their inherent stability, low immunogenicity, and targeted delivery capabilities. This review critically evaluates the transformative potential of exosome-based modalities across pharmaceutical and precision medicine landscapes. Because of their precise targeted biomolecular cargo delivery, exosomes are posited as ideal candidates in drug delivery, enhancing regenerative medicine strategies, and advancing diagnostic technologies. Despite the significant market growth projections of exosome therapy, its utilization is encumbered by substantial scientific and regulatory challenges. These include the lack of universally accepted protocols for exosome isolation and the complexities associated with navigating the regulatory environment, particularly the guidelines set forth by the U.S. Food and Drug Administration (FDA). This review presents a comprehensive overview of current research trajectories aimed at addressing these impediments and discusses prospective advancements that could substantiate the clinical translation of exosomal therapies. By providing a comprehensive analysis of both the capabilities and hurdles inherent to exosome therapeutic applications, this article aims to inform and direct future research paradigms, thereby fostering the integration of exosomal systems into mainstream clinical practice. [ABSTRACT FROM AUTHOR]

Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing vulnerable populations, such as pregnant women and oncological patients. Our objective is to emphasize the critical significance of adopting an integrated approach for the early detection and appropriate management of long COVID. The incidence and severity of long COVID symptoms can have a significant impact on the quality of life of patients and the course of disease in the case of pre-existing pathologies. Particularly, in fragile and vulnerable patients, the presence of PASC is related to significantly worse survival, independent from pre-existing vulnerabilities and treatment. It is important try to achieve an early recognition and management. Various mechanisms are implicated, resulting in a wide range of clinical presentations. Understanding the specific mechanisms and risk factors involved in long COVID is crucial for tailoring effective interventions and support strategies. Management approaches involve comprehensive biopsychosocial assessments and treatment of symptoms and comorbidities, such as autonomic dysfunction, as well as multidisciplinary rehabilitation. The overall course of long COVID is one of gradual improvement, with recovery observed in the majority, though not all, of patients. As the research on long-COVID continues to evolve, ongoing studies are likely to shed more light on the intricate relationship between chronic diseases, such as oncological status, cardiovascular diseases, psychiatric disorders, and the persistent effects of SARS-CoV-2 infection. This information could guide healthcare providers, researchers, and policymakers in developing targeted interventions. [ABSTRACT FROM AUTHOR]

Pollution and climate change constitute a combined, grave and pervasive threat to humans and to the life‐support systems on which they depend. Evidence shows a strong association between pollution and climate change on cardiovascular and respiratory diseases, and pulmonary vascular disease (PVD) is no exception. An increasing number of studies has documented the impact of environmental pollution and extreme temperatures on pulmonary circulation and the right heart, on the severity and outcomes of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (PH), on the incidence of pulmonary embolism, and the prevalence and severity of diseases associated with PH. Furthermore, the downstream consequences of climate change impair health care systems' accessibility, which could pose unique obstacles in the case of PVD patients, who require a complex and sophisticated network of health interventions. Patients, caretakers and health care professionals should thus be included in the design of policies aimed at adaptation to and mitigation of current challenges, and prevention of further climate change. The purpose of this review is to summarize the available evidence concerning the impact of environmental pollution and climate change on the pulmonary circulation, and to propose measures at the individual, healthcare and community levels directed at protecting patients with PVD. [ABSTRACT FROM AUTHOR]

While ground-glass opacity, consolidation, and fibrosis in the lungs are some of the hallmarks of acute SAR-CoV-2 infection, it remains unclear whether these pulmonary radiological findings would resolve after acute symptoms have subsided. We conducted a systematic review and meta-analysis to evaluate chest computed tomography (CT) abnormalities stratified by COVID-19 disease severity and multiple timepoints post-infection. PubMed/MEDLINE was searched for relevant articles until 23 May 2023. Studies with COVID-19-recovered patients and follow-up chest CT at least 12 months post-infection were included. CT findings were evaluated at short-term (1–6 months) and long-term (12–24 months) follow-ups and by disease severity (severe and non-severe). A generalized linear mixed-effects model with random effects was used to estimate event rates for CT findings. A total of 2517 studies were identified, of which 43 met the inclusion (N = 8858 patients). Fibrotic-like changes had the highest event rate at short-term (0.44 [0.3–0.59]) and long-term (0.38 [0.23–0.56]) follow-ups. A meta-regression showed that over time the event rates decreased for any abnormality (β = −0.137, p = 0.002), ground-glass opacities (β = −0.169, p < 0.001), increased for honeycombing (β = 0.075, p = 0.03), and did not change for fibrotic-like changes, bronchiectasis, reticulation, and interlobular septal thickening (p > 0.05 for all). The severe subgroup had significantly higher rates of any abnormalities (p < 0.001), bronchiectasis (p = 0.02), fibrotic-like changes (p = 0.03), and reticulation (p < 0.001) at long-term follow-ups when compared to the non-severe subgroup. In conclusion, significant CT abnormalities remained up to 2 years post-COVID-19, especially in patients with severe disease. Long-lasting pulmonary abnormalities post-SARS-CoV-2 infection signal a future public health concern, necessitating extended monitoring, rehabilitation, survivor support, vaccination, and ongoing research for targeted therapies. [ABSTRACT FROM AUTHOR]

Background: Lung function throughout adulthood predicts morbidity and mortality even among adults without chronic respiratory disease. Diet quality may represent a modifiable risk factor for lung function impairment later in life. We investigated associations between nutritionally-rich plant-centered diet and lung function across early and middle adulthood from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Methods: Diet was assessed at baseline and years 7 and 20 of follow-up using the validated CARDIA diet history questionnaire. Plant-centered diet quality was scored using the validated A Priori Diet Quality Score (APDQS), which weights food groups to measure adherence to a nutritionally-rich plant-centered diet for 20 beneficially rated foods and 13 adversely rated foods. Scores were cumulatively averaged over follow-up and categorized into quintiles. The primary outcome was lung function decline, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), measured at years 0, 2, 5, 10, 20, and 30. We estimated the association of APDQS with annual pulmonary function changes and cross-sectional differences in a repeated measures regression model, adjusting for clinically relevant covariates. Results: The study included 3,787 Black and White men and women aged 18–30 in 1985–86 and followed for 30 years. In multivariable repeated measures regression models, individuals in the lowest APDQS quintile (poorest diet) had declines in FEV1 that were 1.6 ml/year greater than individuals in the highest quintile (35.0 vs. 33.4 ml/year, ß ± SE per 1 SD change APDQS 0.94 ± 0.36, p = 0.009). Additionally, declines in FVC were 2.4 ml/year greater in the lowest APDQS quintile than those in the highest quintile (37.0 vs 34.6 ml/year, ß ± SE per 1 SD change APDQS 1.71 ± 0.46, p < 0.001). The association was not different between never and ever smokers (pint = 0.07 for FVC and 0.32 for FEV1). In sensitivity analyses where current asthma diagnosis and cardiorespiratory fitness were further adjusted, results remained similar. Cross-sectional analysis at each exam year also showed significant differences in lung function according to diet after covariate adjustment. Conclusions: In this 30-year longitudinal cohort study, long-term adherence to a nutritionally-rich plant-centered diet was associated with cross-sectional differences in lung function as well as slower decline in lung function, highlighting diet quality as a potential treatable trait supporting long-term lung health. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of infection but also after hospitalization. This is the consequence of the various pathologies associated with long COVID-19, which are still being studied and researched. Lung fibrosis is an important complication after COVID-19, found in up to 71% of patients after discharge. Our research is based on scientific articles indexed in PubMed; in the selection process, we used the following keywords: "lung fibrosis", "fibrosis mediators", "fibrosis predictors", "COVID-19", "SARS-CoV-2 infection", and "long COVID-19". In this narrative review, we aimed to discuss the current understanding of the mechanisms of initiation and progression of post-COVID-19 lung fibrosis (PC-19-LF) and the risk factors for its occurrence. The pathogenesis of pulmonary fibrosis involves various mediators such as TGF-β, legumain, osteopontin, IL-4, IL-6, IL-13, IL-17, TNF-α, Gal-1, Gal-3, PDGF, and FGFR-1. The key cellular effectors involved in COVID-19 lung fibrosis are macrophages, epithelial alveolar cells, neutrophils, and fibroblasts. The main fibrosis pathways in SARS-CoV-2 infection include hypoxemia-induced fibrosis, macrophage-induced fibrosis, and viral-fibroblast interaction-induced fibrosis. [ABSTRACT FROM AUTHOR]

The concentration of cell-type specific extracellular vesicles (EVs) is a promising biomarker for various diseases. However, concentrations of EVs measured by optical techniques such as flow cytometry (FCM) or particle tracking analysis (PTA) in clinical practice are incomparable. To allow reliable and comparable concentration measurements suitable reference materials (RMs) and SI-traceable (SI—International system of units) methods are required. Hollow organosilica beads (HOBs) are promising RM candidates for concentration measurements of EVs based on light scattering, as the shape, low refractive index, and number concentration of HOBs are comparable to EVs of the respective size range that can be detected with current optical instrumentation. Here, we present traceable methods for measuring the particle size distribution of four HOB types in the size range between 200 and 500 nm by small-angle X-ray scattering (SAXS) and atomic force microscopy (AFM), as well as the number concentration by single-particle inductively coupled plasma mass spectrometry (spICP-MS). Based on the size and shape results, traceable reference values were obtained to additionally determine the refractive index of the shell of the HOB samples by FCM. Furthermore, the estimated refractive indexes of the HOBs plausibly agree with the refractive indexes of EVs of corresponding size. Due to their narrow size distribution and their similar shape, and low refractive index, all HOB samples studied are suitable RM candidates for calibration of the measured sample volume by optical methods within the photon wavelength range used, and thus for calibration of number concentration measurements of EVs in the size range indicated. This was confirmed as the number concentration values obtained by PTA and two independent flow cytometric measurements agreed with the concentration reference values obtained by two independent spICP-MS measurements within the calculated uncertainty limits. [ABSTRACT FROM AUTHOR]

Background and Objectives: Assessment of the prothrombotic, proinflammatory, and functional status of a cohort of COVID-19 patients at least two years after the acute infection to identify parameters with potential therapeutic and prognostic value. Materials and Methods: We conducted a retrospective, descriptive study that included 117 consecutive patients admitted to Iasi Pulmonary Rehabilitation Clinic for reassessment and a rehabilitation program at least two years after a COVID-19 infection. The cohort was divided into two groups based on the presence (n = 49) or absence (n = 68) of pulmonary fibrosis, documented through high-resolution computer tomography. Results: The cohort comprises 117 patients, 69.23% females, with a mean age of 65.74 ± 10.19 years and abnormal body mass index (31.42 ± 5.71 kg/m2). Patients with pulmonary fibrosis have significantly higher levels of C-reactive protein (CRP) (p < 0.05), WBC (7.45 ± 7.86/mm3 vs. 9.18 ± 17.24/mm3, p = 0.053), neutrophils (4.68 ± 7.88/mm3 vs. 9.07 ± 17.44/mm3, p < 0.05), mean platelet volume (MPV) (7.22 ± 0.93 vs. 10.25 ± 0.86 fL, p < 0.05), lactate dehydrogenase (p < 0.05), and D-dimers (p < 0.05), but not ferritin (p = 0.470), reflecting the chronic proinflammatory and prothrombotic status. Additionally, patients with associated pulmonary fibrosis had a higher mean heart rate (p < 0.05) and corrected QT interval (p < 0.05). D-dimers were strongly and negatively correlated with diffusion capacity corrected for hemoglobin (DLCO corr), and ROC analysis showed that the persistence of high D-dimers values is a predictor for low DLCO values (ROC analysis: area under the curve of 0.772, p < 0.001). The results of pulmonary function tests (spirometry, body plethysmography) and the 6-minute walk test demonstrated no significant difference between groups, without notable impairment within either group. Conclusions: Patients with COVID-19-related pulmonary fibrosis have a persistent long-term proinflammatory, prothrombotic status, despite the functional recovery. The persistence of elevated D-dimer levels could emerge as a predictive factor associated with impaired DLCO. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated great potential implications for the gut–lung axis in lung disease etiology and treatment. The gut environment can be influenced by diet, metabolites, microbiotal composition, primary diseases, and medical interventions. These changes modulate the functions of alveolar macrophages (AMs) to shape the pulmonary immune response, which greatly impacts lung health. The immune modulation of AMs is implicated in the pathogenesis of various lung diseases. However, the mechanism of the gut– lung axis in lung diseases has not yet been determined. This mini-review aimed to shed light on the critical nature of communication between the gut and AMs during the development of pulmonary infection, injury, allergy, and malignancy. A better understanding of their crosstalk may provide new insights into future therapeutic strategies targeting the gut–AM interaction. [ABSTRACT FROM AUTHOR]