Luis Hernández-Blasco

Background/Objectives: Obstructive sleep apnea (OSA) and pulmonary embolism (PE) share several risk factors, while emerging evidence suggests a potential pathophysiological link beyond these common determinants. We aimed to characterize the prevalence and severity of OSA in patients with acute PE and to investigate whether the apnea–hypopnea index (AHI) is independently associated with PE and its clinical course. Methods: In this prospective, single-center, case–control study, 128 consecutive patients with acute PE and 252 outpatient controls with other respiratory diseases underwent home respiratory polygraphy. In patients with PE, the sleep study was performed at least three months after the acute event. OSA was diagnosed and graded according to international consensus criteria. Logistic regression models were used to evaluate associations between AHI and PE, acute PE severity, chronic deep vein thrombosis (DVT), and venous thromboembolism (VTE) recurrence. Results: OSA was present in 55.5% of patients with PE, with severe OSA in 28.9%, compared with 42.1% and 13.9%, respectively, among controls (p = 0.013 and p = 0.001). Patients with PE had a higher AHI (21.21 ± 19.29 vs. 14.81 ± 14.26 events/h; p = 0.007) and oxygen desaturation index (19.86 ± 18.77 vs. 13.30 ± 13.79; p = 0.003). Each 10-events/h increase in AHI was independently associated with PE after adjustment for age, sex, BMI, and established VTE risk factors (OR 1.205, 95% CI 1.019–1.426; p = 0.029). AHI was not independently associated with intermediate–high/high-risk PE or chronic DVT. Among patients who discontinued anticoagulation, VTE recurrence was higher in those with OSA (36.0% vs. 13.3%; p = 0.049). Conclusions: OSA is highly prevalent and frequently severe in patients with acute PE. Increasing AHI is independently associated with the presence of PE, supporting a clinically relevant association between sleep-disordered breathing and thromboembolic disease. Because OSA was not systematically reassessed after documented resolution of PE, persistence of OSA independently of residual thromboembolic disease cannot be definitively established. Whether the observed association between OSA and recurrent VTE after anticoagulation withdrawal is confirmed in larger prospective studies remains to be determined.

Background/Objectives: Obstructive sleep apnea (OSA) and pulmonary embolism (PE) share several risk factors, while emerging evidence suggests a potential patho-physiological link beyond these common determinants. We aimed to characterize the prevalence and severity of OSA in patients with acute PE and to investigate whether the apnea-hypopnea index (AHI) is independently associated with PE and its clinical course. Methods: In this prospective, single-center, case–control study, 128 consecu-tive patients with acute PE and 252 outpatient controls with other respiratory diseases underwent home respiratory polygraphy. In patients with PE, the sleep study was per-formed at least three months after the acute event. OSA was diagnosed and graded according to international consensus criteria. Logistic regression models were used to evaluate associations between AHI and PE, acute PE severity, chronic deep vein thrombosis (DVT), and venous thromboembolism (VTE) recurrence. Results: OSA was present in 55.5% of patients with PE, with severe OSA in 28.9%, compared with 42.1% and 13.9%, respectively, among controls (p = 0.013 and p = 0.001). Patients with PE had a higher AHI (21.21 ± 19.29 vs. 14.81 ± 14.26 events/h; p = 0.007) and oxygen desatura-tion index (19.86 ± 18.77 vs. 13.30 ± 13.79; p = 0.003). Each 10-events/h increase in AHI was independently associated with PE after adjustment for age, sex, BMI, and estab-lished VTE risk factors (OR 1.205, 95% CI 1.019–1.426; p = 0.029). AHI was not inde-pendently associated with intermediate-high/high-risk PE or chronic DVT. Among pa-tients who discontinued anticoagulation, VTE recurrence was higher in those with OSA (36.0% vs. 13.3%; p = 0.049). Conclusions: OSA is highly prevalent and frequently severe in patients with acute PE. Increasing AHI is independently associated with the presence of PE, supporting a clinically relevant link between sleep-disordered breath-ing and thromboembolic disease. Whether OSA contributes to recurrent VTE after an-ticoagulation withdrawal requires confirmation in larger prospective studies.

Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC).

Background: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous com-pounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt published, we discarded the option of a systematic review (PRISMA Method). Instead we have done a description of therapies with these results and tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 pa-tients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflam-mation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs on the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in the Long-COVID. Even more, their combination with other therapies is also analyzed. Con-clusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may be-come an integral part of treatment strategies for severe COVID-19, particularly in ad-dressing immune-related lung injury and promoting recovery. However, a full patho-genic mechanism which may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequealae (PASC).

Introduction: The prognosis of asthma has improved significantly since the availability of monoclonal antibodies (mAbs). However, there are no robust predictive markers of response to help clinicians select one of the multiple biologicals recommended in clinical practice guidelines. The aim of this study was to evaluate the utility of basophil reactivity, measured through the basophil activation test (BAT), as a marker of response to mAbs. Methods: We measured basophil reactivity, using anti-immunoglobulin E (anti-IgE) antibodies as a stimulus, in 72 consecutive patients with severe uncontrolled asthma before initiation of treatment with mAbs. Forty-nine patients received omalizumab, 28 received mepolizumab, and 23 received benralizumab at some point. The Spanish Asthma Management Guidelines (GEMA) informed clinical management throughout the study. We studied clinical characteristics, laboratory values, and measures of respiratory function and asthma control. Results: Basophil reactivity (at the highest anti-IgE dilution at which basophil activation was positive) was inversely associated with asthma control and response to any mAb. The patients with higher basophil reactivity (≥ 29% versus < 29%) had lower mAb complete response, more frequent mAb switches, and worse baseline lung function and Asthma Control Test (ACT) scores. The BAT was associated with poor response above the cut-off values of 10.5% for mepolizumab, 15.5% for omalizumab, and 28% for benralizumab. Conclusion: Patients with basophil reactivity greater than or equal to 29% were less likely to achieve full control of asthma when treated with omalizumab, mepolizumab, or benralizumab, independently of classic clinical or biological markers of type 2 asthma.

Background and Objectives: Different cellular and molecular processes are involved in the production of malignant and infectious pleural effusions. However, the underlying mechanisms responsible for these differences or their consequences remain incompletely understood. The objective of this study was to identify differences in gene expression in pleural exudates of malignant and infectious aetiology and establish the possible different biological processes involved in both situations. Materials and Methods: RNA transcriptomic analysis was performed on 46 pleural fluid samples obtained during diagnostic thoracocenteses from 46 patients. There were 35 exudates (19 malignant and 16 infectious effusions) and 11 transudates that were used as a reference control group. Differential gene expression analysis for both exudative groups was identified. An enrichment score using the Human Kegg Orthology database was used for establishing the biological processes associated with malignant and infectious pleural effusions. Results: When comparing malignant exudates with infectious effusions, 27 differentially expressed genes with statistical significance were identified. Network analysis showed ten different biological processes for malignant and for infectious pleural effusions. In malignant fluids, processes related to protein synthesis and processing predominate. In infectious exudates, biological processes in connection with ATP production prevail. Conclusions: This study demonstrates differentially expressed genes in malignant and infectious pleural effusions, which could have important implications in the search for diagnostic or prognostic biomarkers. In addition, for the first time, biological processes involved in these two causes of pleural exudates have been described.

Globally, a leg is amputated approximately every 30 seconds, with an estimated 85 percent of these amputations being attributed to complications arising from diabetic foot ulcers (DFU), as stated by the American Diabetes Association. Peripheral arterial disease (PAD) is a risk factor resulting in DFU and can, either independently or in conjunction with diabetes, lead to recurring, slow-healing ulcers and amputations. According to guidelines amputation is the recommended treatment for patients with no-option critical ischemia of the limb (CTLI). In this article we propose cell therapy as an alternative strategy for those patients. We also suggest the optimal time-frame for an effective therapy, such as implanting autologous mononuclear cells (MNCs), autologous and allogeneic mesenchymal stromal cells (MSC) as these treatments induce neuropathy relief, regeneration of the blood vessels and tissues, with accelerated ulcer healing, with no serious side effects, proving that advanced therapy medicinal product (ATMPs) application is safe and effective and, hence, can significantly prevent limb amputation.

The new radiological diagnostic criteria for diagnosing idiopathic pulmonary fibrosis (IPF) seek to optimize the indications for surgical lung biopsy (SLB). We applied the new criteria to a retrospective series of patients with interstitial lung disease (ILD) who underwent SLB in order to analyse the correlation between the radiological findings suggestive of another diagnosis (especially mosaic attenuation and its location with respect to fibrotic areas) and the usual interstitial pneumonia (UIP) pathologic diagnosis. Two thoracic radiologists reviewed the HRCT images of 83 patients with ILD and SLB, describing the radiological findings and patterns based on the new criteria. The association of each radiological finding with radiological patterns and histology was analysed. Mosaic attenuation is highly prevalent in both the UIP and non-UIP pathologic diagnosis and with similar frequency (80.0% vs. 78.6%). However, the presence of significant mosaic attenuation (≥ 3 lobes) only in non-fibrotic areas was observed in 60.7% of non-UIP pathologic diagnosis compared to 20.0% in UIP. This finding was associated with other diagnoses different from IPF, mostly connective tissue disease-associated interstitial lung disease (CTD-ILD) and hypersensitivity pneumonitis (HP). In our series of pathologically confirmed ILD, mosaic attenuation in non-fibrotic areas was a predictor of non-UIP pathologic diagnosis, and was associated with other diagnoses different from UIP, mostly CTD-ILD and HP. If confirmed in larger series, this finding could constitute a valuable tool for improving the interpretation of radiological patterns.