Borja Recalde-Zamacona’s research while affiliated with Fundación Jiménez Díaz and other places

Background and Methods Surgery remains the standard of care for non‐small cell lung cancer (NSCLC) but is applicable to ≤ 30% of patients. Pulsed Electric Fields (PEF) ablation uses short‐duration, high‐voltage electrical pulses to induce cell death without relying on thermal mechanisms. Safety findings are reported from a two‐arm, non‐randomized, study evaluating the use of PEF in patients with early‐stage NSCLC. Methods PEF energy was delivered bronchoscopically or percutaneously to 36 patients with suspected or confirmed early‐stage NSCLC approximately 20 days before resection; 8 control patients had biopsy only. The primary safety analysis was the device and/or procedure related serious adverse events (AEs) rate from PEF procedure through resection. Immunohistochemical evaluation of resected tissue was also assessed. Results PEF was delivered to all patients in the treatment group after biopsy of targeted tumor. No device or procedure‐related AE were observed. Histopathological assessment of resected tumors demonstrated a cellular depletion zone characterized by decrease or absence of tumor cellularity and a variable degree of inflammation. Tertiary lymphoid structures were observed within PEF‐treated tumors. Conclusions These clinical observations and histopathologic tissue alterations, indicate that PEF energy delivery is feasible and safe in NSCLC, with potential signals of immune system activation.

Introduction: Interventional pneumology plays a crucial role in the diagnosis of peripheral pulmonary lesions (PPLs), offering a minimally invasive approach with a low risk of complications. Iriscope® is a novel device that provides a direct and real-time image of PPLs. The objective of this study was to demonstrate the feasibility and impact of Iriscope® in diagnosing PPLs by analyzing its ability to directly visualize lesions and support accurate sampling during radial probe endobronchial ultrasound (rEBUS) and electromagnetic navigation bronchoscopy (ENB) combined with rEBUS. Methods: A single-center prospective study was conducted from December 2022 to October 2023 on patients with suspicious PPLs. The diagnostic approach involved either rEBUS alone or in combination with ENB. In all cases, an additional novel technique called Iriscope® (Lys Medical, Charleroi, Belgium) was also applied. Iriscope® findings of each lesion were evaluated individually by three expert interventional pulmonologists. Results: Seventy PPLs suspected of malignancy were included in the study. The PPLs underwent examination by ENB combined with rEBUS (55) or by rEBUS alone (15). Diagnosis was obtained in 68.6% (48/70) of cases. Iriscope® provided a direct, real-time view of 57.1% (40/70) of PPLs with a positive predictive value of 92.5% (37/40). This technique was able to visualize 72% (39/54) of malignant lesions, while only 6.1% (1/16) of benign lesions showed pathologic changes. The most common findings observed with Iriscope® were mucosal thickening and infiltration (92.5%), increased capillary vascularization (82%), pale or grayish mucosa (72.5%), obstruction with accumulation of secretions (50%), and cobblestone mucosa (15%). Conclusion: Iriscope® is a promising technique in the diagnostic process of PPLs, providing real-time pathologic imaging that facilitates accurate sampling. Further studies are needed to evaluate success rate of Iriscope-mediated repositioning and to establish predictive patterns for malignant or even benign diseases.

Background: Excessive inflammation is pathogenic in the pneumonitis associated with severe COVID-19. Neutrophils are among the most abundantly present leukocytes in the inflammatory infiltrates and may form neutrophil extracellular traps (NETs) under the local influence of cytokines. NETs constitute a defense mechanism against bacteria, but also have been shown to mediate tissue damage in a number of diseases. Research question: Could NETs and their tissue-damaging properties inherent to neutrophil-associated functions play a role in the respiratory failure seen in patients with severe COVID-19, and how does this relate to the SARS-CoV-2 viral loads, IL-8 (CXCL8) chemokine expression, and cytotoxic T-lymphocyte infiltrates? Study design and methods: Sixteen lung biopsy samples obtained immediately after death were analyzed methodically as exploratory and validation cohorts. NETs were analyzed quantitatively by multiplexed immunofluorescence and were correlated with local levels of IL-8 messenger RNA (mRNA) and the density of CD8+ T-cell infiltration. SARS-CoV-2 presence in tissue was quantified by reverse-transcriptase polymerase chain reaction and immunohistochemistry analysis. Results: NETs were found in the lung interstitium and surrounding the bronchiolar epithelium with interindividual and spatial heterogeneity. NET density did not correlate with SARS-CoV-2 tissue viral load. NETs were associated with local IL-8 mRNA levels. NETs also were detected in pulmonary thrombi and in only one of eight liver tissues. NET focal presence correlated negatively with CD8+ T-cell infiltration in the lungs. Interpretation: Abundant neutrophils undergoing NETosis are found in the lungs of patients with fatal COVID-19, but no correlation was found with viral loads. The strong association between NETs and IL-8 points to this chemokine as a potentially causative factor. The function of cytotoxic T-lymphocytes in the immune responses against SARS-CoV-2 may be interfered with by the presence of NETs.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) disease (COVID-19) is a novel threat that hampers life expectancy especially in obese individuals. Though this association is clinically relevant, the underlying mechanisms are not fully elucidated. SARS CoV2 enters host cells via the Angiotensin Converting Enzyme 2 receptor, that is also expressed in adipose tissue. Moreover, adipose tissue is also a source of many proinflammatory mediators and adipokines that might enhance the characteristic COVID-19 cytokine storm due to a chronic low-grade inflammatory preconditioning. Further obesity-dependent thoracic mechanical constraints may also incise negatively into the prognosis of obese subjects with COVID-19. This review summarizes the current body of knowledge on the obesity-dependent circumstances triggering an increased risk for COVID-19 severity, and their clinical relevance.

Background SARS‐CoV‐2, the COVID‐19 causative agent, has infected millions of people and killed over 1.6 million worldwide. A small percentage of cases persist with prolonged positive RT‐PCR on nasopharyngeal swabs. The aim of this study was to determine risk factors for prolonged viral shedding among patient’s basal clinical conditions. Methods We have evaluated all 513 patients attended in our hospital between March 1 and July 1. We have selected all 18 patients with prolonged viral shedding, and compared them with 36 sex‐matched randomly selected controls. Demographic, treatment and clinical data were systematically collected. Results Global median duration of viral clearance was 25.5 days (n=54; IQR, 22–39.3 days), 48.5 days in cases (IQR 38.7‐54.9 days) and 23 days in controls (IQR 20.2‐25.7), respectively. There were not observed differences in demographic, symptoms or treatment data between groups. Chronic rhino‐sinusitis and atopy were more common in patients with prolonged viral shedding (67%) compared with controls (11% and 25% respectively) (p<0.001 and p=0,003). The use of inhaled corticosteroids was also more frequent in case group (p=0.007). Multivariate analysis indicated that CRS (odds ratio [OR], 18.78; 95% confidence interval [95%CI],3.89 – 90.59; p<0.001) was independently associated with prolonged SARS‐CoV‐2 RNA shedding in URT samples, after adjusting for initial PCR Ct values. Conclusion We found that chronic rhino‐sinusitis and atopy might be associated with increased risk of prolonged viral shedding. If confirmed in prospective trials, this finding might have clinical implications for quarantine duration due to increased risk of pandemic spread.