Pascual, Jorge M.

Abstract MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies show promise in decreasing mortality in acute respiratory distress syndrome (ARDS) and suggest benefits in treatment of COVID-19-related ARDS. We performed a meta-analysis of published trials assessing the efficacy and adverse events (AE) rates of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through November 3, 2021. Reports in all languages, including randomized clinical trials (RCTs), non-randomized interventional trials, and uncontrolled trials, were included. Random effects model was used to pool outcomes from RCTs and non-randomized interventional trials. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory, and imaging findings. A total of 736 patients were identified from 34 studies, which included 5 RCTs (n = 235), 7 non-randomized interventional trials (n = 370), and 22 uncontrolled comparative trials (n = 131). Patients aged on average 59.4 years and 32.2% were women. When compared with the control group, MSC cell therapy was associated with a reduction in all-cause mortality (RR = 0.54, 95% CI: 0.35-0.85, I 2 = 0.0%), reduction in SAEs (IRR = 0.36, 95% CI: 0.14-0.90, I 2 = 0.0%) and no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared with conventional care. Large-scale double-blinded, well-powered RCTs should be conducted to further explore these results.

AbstractBackgroundEndobronchial ultrasound transbronchial needle aspiration (EBUS‐TBNA) is a safe and minimally invasive procedure for evaluating hilar and mediastinal lymph nodes. The reported sensitivity and specificity of EBUS‐TBNA are 95% and 97%, respectively. A comparison of diagnostic sensitivity for lymph nodes suspected of lung cancer according to needle size in EBUS‐TBNA is needed.ObjectivesTo compare the diagnostic sensitivity of the 19‐G, 21‐G, 22‐G and 25‐G needles for lymph nodes suspected of non‐small cell lung cancer (NSCLC) using EBUS‐TBNA.MethodsA literature search from PubMed, EMBASE, LILACS, DOAJ and CENTRAL through October 2020 was performed by two reviewers. The extracted data were evaluated using STATA® and Open Meta Analyst software for meta‐analysis with a binary method model to compare sensitivity, specificity and summary receiver operating characteristic curve for each needle size.ResultsFourteen studies including 1296 participants were considered for the analysis. The overall sensitivity of EBUS‐TBNA was 88.2% (95% CI 84%, 91%) and 93% (95% CI 88%, 95%) for the 19‐G needle, 87.6% (95% CI 79.6%, 92.8%) for the 21‐G needle and 85% (95% CI 80%, 88%) for the 22‐G needle. The overall sensitivity of EBUS‐TBNA for diagnosing NSCLC was 88.3% (95% CI, 81%, 93%) and 92.9% (95% CI, 85%, 97%) for the 19‐G needle, 89.4% (95% CI 79.4%, 94.8%) for the 21‐G needle and 82.1% (95% CI 66%, 91%) for the 22‐G needle.ConclusionThe 19‐G, 21‐G and 22‐G needles present a similarly high diagnostic sensitivity in EBUS‐TBNA. The 19‐G needle provided better sample adequacy for molecular and immunohistochemical testing, improving diagnostic yield in this subgroup.

AbstractBronchoscopy in thrombocytopenic patients remains a controversial topic as traditionally varying platelet thresholds have been stablished as “safe,” ranging from 20,000 to 50,000. A lower threshold may be safe for a routine airway inspection with bronchoalveolar lavage but will be far from safe for more invasive interventions such as needle biopsy, transbronchial biopsy, or cryo‐biopsy. Currently, a minimal platelet threshold during robotic‐assisted bronchoscopy (RAB) has not been established. In addition, the absolute platelet number does not guarantee appropriate platelet function. The literature regarding the safety of bronchoscopy and its bleeding risk, considering broader and more functional tests such as thromboelastography (TEG), is also lacking. We present our RAB approach to safely sample lung nodules in a patient with thrombocytopenia. Our precautionary strategy for high‐risk bleeding cases during RAB utilizing TEG and parallel flexible bronchoscopy with segmental balloon occlusion may be an appropriate technique to minimize bleeding risk.

AbstractSevere cases of COVID-19 infection, often leading to death, have been associated with variants of acute respiratory distress syndrome (ARDS). Cell therapy with mesenchymal stromal cells (MSCs) is a potential treatment for COVID-19 ARDS based on preclinical and clinical studies supporting the concept that MSCs modulate the inflammatory and remodeling processes and restore alveolo-capillary barriers. The authors performed a systematic literature review and random-effects meta-analysis to determine the potential value of MSC therapy for treating COVID-19-infected patients with ARDS. Publications in all languages from 1990 to March 31, 2020 were reviewed, yielding 2691 studies, of which nine were included. MSCs were intravenously or intratracheally administered in 117 participants, who were followed for 14 days to 5 years. All MSCs were allogeneic from bone marrow, umbilical cord, menstrual blood, adipose tissue, or unreported sources. Combined mortality showed a favorable trend but did not reach statistical significance. No related serious adverse events were reported and mild adverse events resolved spontaneously. A trend was found of improved radiographic findings, pulmonary function (lung compliance, tidal volumes, PaO2/FiO2 ratio, alveolo-capillary injury), and inflammatory biomarker levels. No comparisons were made between MSCs of different sources.Significance statement The potential benefits of mesenchymal stromal cell (MSC) therapy for patients with COVID-19 acute respiratory distress syndrome support the rapid commencement of clinical trials, as well as the compassionate use of MSCs that already have documented safety profiles from FDA-approved studies.