Thorax Foundation

Abstract INTRODUCTION. Actinomycosis is a rare infection, caused by Gram positive anaerobic and filamentous bacteria that usually colonize human mucosa. Infection is produced chronically in immunosuppressed or immunocompetent patients. We report the case of a 41 year old male presenting chronic cough, diagnosed with Atypical Pneumonia with histopathological compatibility with infection by Actinomyces Sp. CLINICAL CASE. A 41-year-old male from Toluca, Estado de México, attended an evaluation after 2 months of chronic cough, associated with dyspnea and yellow sputum. Known with gastroesophageal reflux disease, rhinitis and asthma on partial control with inhaled and systemic corticoids and bronchodilators. Before referral, he received empiric antibiotics with no response. Helicoidal CT was performed with multiple nodules, patchy condensates in the lower right lobe pulmonary and right hilar calcifications. A broncho alveolar lavage and transbronchial lung biopsies were performed which revealed respiratory mucosa with severe chronic and acute inflammation associated with infection caused by organisms that are morphologically compatible with Actinomyces Sp. The patient receives treatment for 4 weeks with intravenous ceftriaxone and was given to the patient subsequently treatment with oral amoxicillin for 6 month with resolution of the Pneumonia clinically and by image. The patient has been followed up with pulmonary function tests which improved with time and no recurrence of the infection was noted. The patient is currently asymptomatic, with no evidence of systemic inflammatory response and with good control of rhinitis and asthma.CONCLUSION: Infection by Actinomyces Sp. is rare, usually presenting as a chronic suppurative infection. Immunosuppression is a classic risk factor, but infection can happen in the immunocompetent. The imaging for actinomycosis is nonspecific. In the acute presentation, it can look like any other pneumonia. In chronic forms, it can present as a pulmonary mass or can cavitate. Epidemiology hasn't been established because of the low incidence of this disease.

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<bold>Background:</bold> Respiratory muscle and small airways function may be affected following hospitalisation due to SARS-COV-2 infection. <bold>Aim:</bold> To investigate the association between small airway function and respiratory muscle strength in individuals with long COVID-19 syndrome. <bold>Methods:</bold> Thirty-three patients [age (mean±SD): 53±11years and BMI: 28±5.5 Kg·m-2] were included in the analysis 149±90 days following hospital discharge. Routine lung function testing was performed. Respiratory muscle function was assessed by measuring maximum static inspiratory (PImax) and expiratory (PEmax) mouth pressure using a semi-rigid flanged mouthpiece fitted to a metallic stem incorporating a 3-way tap. Small airway function was evaluated by the single breath nitrogen washout test. <bold>Results:</bold> FEV₁ %pred was 100±19, TLC %pred was 94±27, and DLco %pred was 78±23%. None of the patients presented with obstructive ventilatory defect. PImax (68±32%) and PEmax (73±33%) were reduced in 19 and 22 patients respectively. Eight patients had tidal airway closure as their open capacity (OC) was less than their inspiratory capacity (IC) (OC-IC= -0.140±0.090 L). The slope of phase III (71±52%) was abnormal in 3 patients. Closing capacity (CC) (115±28%) was abnormal in 14 patients. PImax correlated with OC (r=0.532, p=0.002) and OC-IC (r=0.482, p=0.005), whilst PEmax correlated with OC (r=0.614, p=0.001) and CC/TLC (r=0.411, p=0.019). OC-IC was associated with Pimax %pred and Pemax %pred, (r=0.470, p=0.007) and (r=0.352, p=0.05), respectively. <bold>Conclusions:</bold> Respiratory muscle and small airway function are affected in a subgroup of patients with long covid-19 syndrome. Respiratory muscle strength is associated with small airways function.

Non-small cell lung cancer (NSCLC) constitutes one of the deadliest and most common malignancies. The LKB1/STK11 tumour suppressor is mutated in ∼ 30% of NSCLCs, typically lung adenocarcinomas (LUAD). We implemented zebrafish and human lung organoids as synergistic platforms to pre-clinically screen for metabolic compounds selectively targeting LKB1-deficient tumours. Interestingly, two kinase inhibitors, Piceatannol and Tyrphostin 23, appeared to exert synthetic lethality with LKB1 mutations. Although LKB1 loss alone accelerates energy expenditure, unexpectedly we find that it additionally alters regulation of the key energy homeostasis maintenance player leptin (LEP), further increasing the energetic burden and exposing a vulnerable point; acquired sensitivity to the identified compounds. We show that compound treatment stabilises Hypoxia-inducible factor 1-alpha (HIF1A) by antagonising Von Hippel-Lindau (VHL)-mediated HIF1A ubiquitination, driving LEP hyperactivation. Importantly, we demonstrate that sensitivity to piceatannol/tyrphostin 23 epistatically relies on a HIF1A-LEP-Uncoupling Protein 2 (UCP2) signaling axis lowering cellular energy beyond survival, in already challenged LKB1-deficient cells. Thus, we uncover a pivotal metabolic vulnerability of LKB1-deficient tumours, which may be therapeutically exploited using our identified compounds as mitochondrial uncouplers.

Im Rahmen einer Videopräsentation möchten wir einen spannenden Fall einer 60-jährigen Patientin vorstellen, die aufgrund einer Schmetterling aussehender Läsion im hinteren Mediastinum, die sich in der Pleurahöhle mit einem Kontakt mit der Lunge beidseits ausgebreitet hat zur weiteren Diagnose und Behandlung überwiesen wurde. Die Entdeckung dieser Läsion erfolgte zufällig während einer CT-Untersuchung von Brust und Bauch, die aufgrund erhöhter CA 19-9-Werte in routinemäßigen Bluttests durchgeführt wurde. Trotz bereits zweier Biopsien (eine CT-gesteuerte und eine durch endoskopischen Ultraschall) zum Zeitpunkt der Überweisung blieb die histopathologische Untersuchung leider nicht eindeutig.

Einleitung Bei Patienten mit interstitieller Lungenerkrankung und fehlendem eindeutigen UIP-Muster in der CT sollte eine invasive Diagnostik zur Abklärung erwogen werden. In der vorliegenden Analyse wurden klinische Prädiktoren für das Vorliegen einer idiopathischen Lungenfibrose untersucht.

<b>Rationale:</b> Progressive pulmonary fibrosis (PPF) can occur in the context of many of fibrotic interstitial lung diseases (f-ILD). In later phases, common immune mechanisms that lead to self-perpetuating fibrosis might play a role. <b>Objective:</b> We investigated if the peripheral blood immunological profile may differ in PPF patients from non-progressive f-ILD (non-PPF), as well as in relation to their clinical severity. <b>Methods:</b> Flow cytometric staining was performed on whole blood from 33 patients with f-ILD at diagnosis (11 PPF, and 22 non-PPF patients). All patients were treated following international guidelines and followed up one year when they were categorized as stable or progressors based on worsening respiratory symptoms, radiological evidence of disease progression, and/or decline of either forced vital capacity (FVC) or predicted carbon monoxide diffusing capacity (DLCO). Baseline immune populations were compared across groups. <b>Results:</b> In the f-ILD cohort we found: 1) a significant negative correlation between baseline FVC and CD8+HLA-DR+T cells, and central memory CD4+T cells; 2) a significant negative correlation between both baseline FVC and DLCO and the percentage of T helper type 1 (Th1) cells and CD4+CD28-HLA-DR+T cells. Compared to non-PPF, patients with PPF showed: 1) higher percentage of NK-T like cells; 2) a significant negative correlation between baseline FVC and the percentage of CD8 T cells. <b>Conclusion:</b> the peripheral blood immunologic profiling of patients with f-ILD present common abnormalities, with an aged blood immune profile that is mainly associated with impaired lung function. Moreover, there is an increased cytotoxic immune response in PPF patients.