Pulmonary Pathology Research Articles

Heterogeneity of Inflammatory Processes and Pathways Driving Chronic Obstructive Pulmonary Disease Pathology

Two symposia occurred during the European Respiratory Society (ERS) Congress 2024, highlighting the heterogeneity in chronic inflammatory pathways that underlie chronic obstructive pulmonary disease (COPD) pathophysiology. In 'A Breath of Fresh Air: A Greater Understanding of COPD With Type 2 Inflammation', Henrik Watz (Chair), German Center for Lung Research, Grosshansdorf, Germany, provided an overview of both the pathophysiology and the burden of disease of COPD. He discussed how exacerbations, which may be increased in those with evidence of Type 2 inflammation, contribute to the cycle of worsening COPD. Mona Bafadhel, King’s College London, UK, provided an examination of the mechanisms and biomarkers of Type 2 inflammation in COPD. Finally, Alberto Papi, University of Ferrara, Italy, summarised the latest research on biological treatments targeting Type 2 inflammation in COPD. The second symposium, 'Targeting interleukin-33 (IL-33) in COPD: Exploring New Frontiers for COPD Management', discussed inflammation in COPD, focusing on the central role of IL-33 as a mediator for both Type 2 and Type 1/Type 3 inflammation. Klaus Rabe (Chair), LungenClinic, Grosshansdorf, Germany, reviewed the structure and function of IL-33 and its initial processes that lead to downstream immune responses. Stephanie Christenson, University of California, San Francisco, USA, explored how genetic and environmental factors contribute to IL-33 activity in COPD pathology. Next, Paola Rogliani, University of Rome ‘Tor Vergata’, Italy, presented an examination of IL-33 inflammatory processes and evidence from COPD animal models illustrating the role of IL-33 in airway inflammation and lung function decline. Klaus Rabe concluded with an examination of IL-33 as a target for new COPD treatment approaches.

Pathomorphological Features of Lung Fibrosis in Individuals Occupationally Exposed to Alpha Radiation

The aim of this study was to search for the specific morphological features of radiation-induced lung fibrosis compared to pulmonary fibrosis of another origin, using biological specimens of lung tissue collected from workers internally exposed to alpha radiation. The morphological features of lung fibrosis were defined using biological specimens of lung tissue that had been collected during autopsy examinations from 56 workers diagnosed with plutonium-induced lung fibrosis during life, from 34 workers with lung fibrosis of another origin (due to chronic inflammatory lung diseases) and from 35 workers without clinical pulmonary pathology (controls). The total lung-absorbed dose of gamma radiation from external exposure did not significantly differ among the studied groups, and the total lung-absorbed dose of alpha radiation from internal exposure was significantly higher in workers with plutonium-induced lung fibrosis. To investigate the extracellular matrix components, mono- and polyclonal labeled antibodies against type I, IV, and V collagens were used. In addition, to evaluate the system of extracellular matrix metabolism regulation, the antibodies against matrix metalloproteinases MMP-2, MMP-9, tissue inhibitors of matrix metalloproteinases TIMP-1 and TIMP-2 were used. The study revealed qualitative and quantitative morphological peculiarities of plutonium-induced lung fibrosis compared to lung fibrosis of another origin. This allows us to conclude that plutonium-induced lung fibrosis is a specific type of lung fibrosis, which is characterized with specific location and architectonics of fibrosis foci within the lung, and with changes in levels of collagen, elastic and reticular fibers in the pulmonary stroma. The analysis demonstrated that hyperproduction of type V collagen plays a key role in the development of plutonium-induced lung fibrosis. In addition, the imbalance between the expression of MMPs and their inhibitors plays an important role in the development of lung fibrosis.

Cold ischemia time alters cell-type specific senescence leading to loss of cellular integrity in mouse lungs

Purpose: Ischemia-reperfusion injury (IRI) is a major challenge in lung transplantation often causing graft dysfunction and chronic airway illnesses in recipients. To prevent potential transplant related complications, strict guidelines were put in place to choose viable donor lungs with minimal risk of IRI. These regulations deem most of the donor organs unfit for transplant which then are donated for research to understand the mechanisms of health and diseases in human. However, resected organs that are being transported undergo cold ischemia that can negatively affect the tissue architecture and other cellular functions under study. Thus, it is important to assess how cold ischemia time (CIT) affects the physiological mechanism. In this respect, we are interested in studying how CIT affects cellular senescence in normal aging and various pulmonary pathologies. We thus hypothesized that prolonged CIT exhibits cell-type specific changes in lung cellular senescence in mice. Methods: Lung lobes from C57BL/6J (n = 5–8) mice were harvested and stored in UW Belzer cold storage solution for 0, 4-, 9-, 12-, 24-, and 48-h CIT. Lung cellular senescence was determined using fluorescence (C12FdG) assay and co-immunolabelling was performed to identify changes in individual cell types. Results: We found a rapid decline in the overall lung cellular senescence after 4-h of CIT in our study. Co-immunolabelling revealed the endothelial cells to be most affected by cold ischemia, demonstrating significant decrease in the endothelial cell senescence immediately after harvest. Annexin V-PI staining further revealed a prominent increase in the number of necrotic cells at 4-h CIT, thus suggesting that most of the cells undergo cell death within a few hours of cold ischemic injury. Conclusions: We thus concluded that CIT significantly lowers the cellular senescence in lung tissues and must be considered as a confounding factor for mechanistic studies in the future.

Case Report: Aspirated Airway Foreign Body Mimicking Endobronchial Mass: A Diagnostic Challenge

Abstract Introduction/Objective Despite advancements in imaging modalities, identifying retained foreign bodies within the lung remains arduous. Detecting small foreign bodies is crucial as they can serve as a focal point for subsequent infections. Initial assessments may mimic malignancy. Herein, we present a case of a retained foreign body masquerading as an endobronchial mass, accompanied by unilateral pleural effusion and persistent hypoxia. Subsequent bronchoscopy showed a pearly white endobronchial mass partially obstructing the segmental bronchus at the posterior basal segment of the right lower lobe of lung with accompanying right pleural effusion and atelectasis. Methods/Case Report This is a 58-year-old male with history of hypertension, deep vein thrombosis, transient ischemic attack, and a recent motor vehicle accident with blunt chest trauma. He had a thoracic spinal cord transection with grade III blunt thoracic aortic injury, developed anasarca, hypoxia, right pleural fluid requiring multiple thoracentesis, and right sided hemothorax requiring massive transfusion protocol. Subsequent evaluations, including bronchoscopic transbronchial forceps biopsies and bronchial wash and pleural fluid cytologic examinations showed no malignant cells. Repeat bronchoscopy was concerning for enlarging mass and obstruction. Bronchoscopy almost 2 months after MVA revealed an endobronchial foreign body (tooth) lodged in the left lower lobe of lung posterior segment. Results (if a Case Study enter NA) N/A Conclusion While aspiration of foreign bodies into the tracheobronchial tree is not uncommon especially in children, foreign bodies, particularly teeth, are rare in adults. Bronchial foreign body aspiration may occur in trauma, with diagnosis typically relying on history and physical examination. Detection remains challenging despite imaging advancements, with implications including infection nidus formation. In our case, delayed diagnosis highlights the importance of considering unusual etiologies in persistent pulmonary pathology. Retrospective imaging analysis and CT findings suggested a foreign body, emphasizing the utility of imaging in suspected cases. Prompt surgical intervention is crucial to prevent complications such as recurrent infections.

FPR1 signaling aberrantly regulates S100A8/A9 production by CD14+FCN1hi macrophages and aggravates pulmonary pathology in severe COVID-19

Excessive alarmins S100A8/A9 escalate the inflammation and even exacerbate immune-driven thrombosis and multi-organ damage. However, the regulatory mechanisms of S100A8/A9 expression in infectious diseases remain unclear. In this study, high-dimensional transcriptomic data analyses revealed a high proportion of CD14+FCN1hi macrophages within the pulmonary niche post-severe SARS-CoV-2 infection. By constructing the S100-coexpression gene list and supervised module scoring, we found that CD14+FCN1hi macrophages presented the highest scores of alarmin S100, and possibly served as the trigger and amplifier of inflammation in severe COVID-19. These CD14+FCN1hi cells lacked the positive regulatory activity of transcription factor PPARγ, and lost their differentiation ability towards mature macrophages. Ex vivo experiments further validated that the epithelial cells with high ORF-3a expression promoted the expression and secretion of S100A8/A9 through ANXA1/SAA1-FPR1 signaling. S100A8/A9 heterodimers, as well as the co-localization of S100A8/A9 with microtubules, were both diminished by the FPR1 inhibitor. Phospho-kinase protein array indicated that STAT3 promoted transcription, and PLC-γ and ERK1/2 pathways were involved in the hetero-dimerization and unconventional secretion of S100A8/A9. Our study highlights the pivotal role of FPR1 signaling in the excessive production of S100A8/A9 and provides a promising target for the prevention and control of severe COVID-19 and post-acute COVID-19 sequelae.

The Thyroid Hormone Analog GC-1 Mitigates Acute Lung Injury by Inhibiting M1 Macrophage Polarization.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life-threatening condition with a high mortality rate of ≈40%. Thyroid hormones (THs) play crucial roles in maintaining homeostasis of the cellular microenvironment under stress. The previous studies confirmed that the clinical-stage TH analog GC-1 significantly alleviates pulmonary fibrosis by improving the function of mitochondria in epithelial cells. However, the effects of GC-1 on macrophages in lung injury and the related mechanisms remain unclear. This study evaluated the therapeutic effects of GC-1 in two murine models of lipopolysaccharide (LPS)- or hydrochloric acid (HCl)-induced ALI. Additionally, mouse alveolar macrophages (AMs) and human THP-1-derived macrophages are utilized to investigate the impact of GC-1 on macrophage polarization. GC-1 effectively reduces the inflammatory response and lung injury in ALI mice, as evidenced by neutrophil infiltration, cytokine levels, alveolar fluid clearance, and pulmonary pathology. Notably, GC-1 selectively inhibits M1 macrophage polarization, which may be achieved by impeding NF-κB signaling activation through the DNMT3b-PPARγ-NF-κB pathway in a TH receptor β1 (TRβ1)-dependent manner, consequently suppressing the polarization of macrophages toward the M1 phenotype and overproduction of inflammatory cytokines. Overall, these findings highlight the immunomodulatory property of GC-1 as an anti-inflammatory strategy for ALI/ARDS and inflammation-related diseases.

LungHist700: A dataset of histological images for deep learning in pulmonary pathology

Accurate detection and classification of lung malignancies are crucial for early diagnosis, treatment planning, and patient prognosis. Conventional histopathological analysis is time-consuming, limiting its clinical applicability. To address this, we present a dataset of 691 high-resolution (1200 × 1600 pixels) histopathological lung images, covering adenocarcinomas, squamous cell carcinomas, and normal tissues from 45 patients. These images are subdivided into three differentiation levels for both pathological types: well, moderately, and poorly differentiated, resulting in seven classes for classification. The dataset includes images at 20x and 40x magnification, reflecting real clinical diversity. We evaluated image classification using deep neural network and multiple instance learning approaches. Each method was used to classify images at 20x and 40x magnification into three superclasses. We achieved accuracies between 81% and 92%, depending on the method and resolution, demonstrating the dataset’s utility.

Use of artificial intelligence-powered ECG to differentiate between cardiac and pulmonary pathologies in patients with acute dyspnoea in the emergency department

BackgroundAcute dyspnoea is common in acute care settings. However, identifying the origin of dyspnoea in the emergency department (ED) is often challenging. We aimed to investigate whether our artificial intelligence...

Scutellaria baicalensis ameliorates allergic airway inflammation through agonism and transcriptional regulation of TAS2Rs

Ethnopharmacological relevanceScutellaria baicalensis Georgi (SCB, Huangqin) is a traditional medicinal plant used to treat fever and respiratory diseases. SCB has a good therapeutic effect on asthma and anti-inflammation in traditional clinic use. However, the molecular mechanism and targets of SCB in treating asthma are still unclear. Aim of the studyCombining transcriptomic analysis and in vitro experimental validation, this study aimed to reveal the molecular mechanism and targets of SCB in treating asthma. Materials and methodsThe anti-asthmatic effects of SCB and its active components, scutellarin and oroxylin A, were evaluated in ovalbumin (OVA)-induced rats by analysis of pulmonary function and pathology. The signaling pathways in rat pulmonary tissue were analyzed using transcriptomics and protein interaction network analysis. Calcium mobilization assay and molecular docking were utilized to discover the active compounds from SCB with agonism activity of type 2 taste receptors (TAS2Rs). The anti-asthmatic effect and transcriptional regulation of TAS2Rs regulated by SCB and its active components were analyzed in vitro. ResultsExtracts of SCB (ESB), scutellarin, and oroxylin A ameliorated airway function and inflammation in OVA-induced rats. The anti-asthma mechanism of ESB, scutellarin and oroxylin A was highly related to immune and taste transduction pathways based on transcriptomic analysis, especially the TAS2Rs signaling pathway. ESB was the direct agonist of TAS2R4 and TAS2R14 with EC50 of 209.1 and 217.2 μg/mL based on calcium mobilization assay, respectively. Baicalein was the main active component for TAS2R4 agonism activity, and scutellarin and oroxylin A had weak agonism activity of TAS2R4 and TAS2R14 through calcium mobilization assay and molecular docking. However, scutellarin and oroxylin A significantly upregulated the gene expression of Tas2r108 (the mouse ortholog of the TAS2R4) in lung tissue. ESB, scutellarin, and oroxylin A inhibited LPS-induced lactate dehydrogenase release and gene expression of TNF through transcriptional regulation of TAS2R4 and TAS2R14 on bronchial epithelial cells. ESB and oroxylin A ameliorated IgE-induced β-hexosaminidase release and gene expression of Il4 and Tnf and upregulated gene expression of Tas2r108. ConclusionThese results provided new insight into the anti-asthmatic mechanism of SCB and active components, scutellarin and oroxylin A, through agonism and transcriptional regulation of TAS2Rs to ameliorate allergic airway inflammation.

P1.06C.01 Evaluation of Small Pulmonary Pathology Specimen Management in the Province of Quebec, Canada

P1.06C.01 Evaluation of Small Pulmonary Pathology Specimen Management in the Province of Quebec, Canada

Clinical cases of aortic dissection with a “pneumonic mask”

The descriptions of two cases of aortic dissection with an atypical picture, erroneously regarded as a pulmonary pathology, are presented. A thorough analysis of the clinical picture and the timely use of imaging diagnostic methods made it possible to establish the correct diagnosis and select presented.

Pregnancy enhances antiviral immunity independent of type I IFN but dependent on IL-17-producing γδ+ T cells in the nasal mucosa.

Pregnancy is associated with profound changes in immunity. However, pregnancy-related respiratory immune adaptations in response to influenza infection and their impact on disease severity remain unclear. Here, we describe, in a preclinical model of mid-gestation pregnancy, a mechanism of enhanced host defense against influenza A virus (IAV) localized to the nasal cavity that limits viral replication and reduces the magnitude of intrapulmonary immune responses. Consequently, the pregnant mice show reduced pulmonary pathology and preserved airway function after IAV infection. The early restriction of viral replication is independent of type I interferon (IFN) but dependent on increased antimicrobial peptides (AMPs) driven by interleukin-17+ (IL-17+) γδ+ T cells within the nasal passages. This pathway of host defense against IAV infection in the upper airways during pregnancy restricts early viral infection and prevents virus dissemination into the lung supporting maternal fitness.

Clinical and immunological characteristics of post-covid patients with infectious immunopathology syndrome

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has caused global morbidity and high mortality worldwide. Today it is known that, despite recovery from COVID-19, confirmed by both laboratory and instrumental diagnostic methods, many patients, regardless of the severity of the disease, suffer from a significant deterioration in health and increased exacerbations of chronic diseases. During examinations by attending physicians, they note fatigue, an increase in cases of acute respiratory viral infections per year, an increase in relapses of skin diseases such as furunculosis, pyoderma, exacerbation of pulmonary pathologies, pathologies of the urinary tract of inflammatory origin, as well as chronic infectious diseases such as herpesvirus and human papillomavirus infections, which occur for the first time or are characterized by frequent relapses no less than six months after recovery from acute COVID-19. Such persistent post-infectious consequences are known as post-COVID syndrome. SARS-CoV-2 infection is accompanied by damage to both the acquired and innate immune systems. In previous work, we determined the role of B cells, cytotoxic T lymphocytes, natural killer cells and the regulatory properties of CD46, as well as its involvement in the processes of viral entry into the cell. In this study, we studied the relationship of immune disorders of these factors of innate and acquired immunity with the clinical manifestations of post-COVID infectious syndrome in this category of patients and the severity of lung damage in these patients during the acute period of COVID-19. The results of the study showed that in some patients more than six months after suffering from COVID-19, the following was revealed: in patients who had a coronavirus infection without lung damage, no violations of the innate and acquired parts of the immune system were detected. In addition, significant differences were identified between clinical manifestations of diseases with increasing cases of relapses or newly identified after clinical recovery from an acute COVID-19 infection, depending on the phenotype of immune status disorders.

Analysis of the course and outcomes of COVID-19 at different stages of the pandemic in hemodialysis patients

The purpose of this study was a comparative analysis of the characteristics of the course and outcomes of COVID-19 in HD patients at different stages of the pandemic, focusing on the of the use of immunomodulatory therapy.Materials and methods. The retrospective study included 897 HD patients with COVID-19 (mean age 60.7 years, M 58.5%) who were hospitalized at Moscow City Hospital № 52. Group 1 (n=720) consisted of patients infected between the end of March 2020 and April 2021, group 2 (n=177) included patients hospitalized in May-December 2021. Each of group was divided into 2 subgroups based on treatment approaches. Subgroup 1a (n=231) included patients of the initial period of the pandemic who did not receive adequate immunomodulatory therapy, while Subgroup 1b (n=489) included patients of the late stage, were treated with IL-6 receptor blockers and corticosteroids. In group 2, 108 patients in Subgroup 2a received similar therapy, while 69 patients in Subgroup 2b were treated with neutralizing monoclonal antibodies in the early stages of the disease.Results. Mortality rates in Group 1 and Group 2 was 20.1% and 14.7%, respectively (p<0.09). The incidence of unfavorable outcome was highest in Subgroup 1a and lowest in Subgroup 2b (31.2% vs 5.8%, p<0.01). Mortality in Subgroups 1b and 2a was comparable (14.9% and 20.4%), despite more severe initial lung damage according to CT data in Subgroup 2a. In these patients, immunomodulators was more frequently combined with therapeutic plasma exchange (TPE). Independent risk factors for an unfavorable outcome were the progression of pulmonary pathology, with the transformation of stages CT 1-2 to CT 3-4, and a high comorbidity index.Conclusions. The use of immunomodulatory drugs imprtoved the effectiveness of COVID-19 treatment in patients with CKD5D. In severe cases, the most favorable outcomes were achieved with a combination of immunobiological drugs, corticosteroids, and TPE. An even more significant reduction in mortality was observed following the introduction of neutralizing monoclonal antibodies into clinical practice. Independent predictors of unfavorable outcome of COVID-19 in HD patients were a high comorbidity index and the progression of CT 1-2 into CT 3-4.

Aerosol of Enoximone/Hydroxypropyl-β-Cyclodextrin Inclusion Complex, Biopharmaceutical Evidence for ARDS Applicability.

Phosphodiesterase (PDE) inhibitors are gaining interest in the context of pulmonary pathologies. In particular, the PDE3 inhibitor enoximone (ENXM) has shown potential relative to the cure of asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS). Despite its administration via inhalation being planned for use against COVID-19 related ARDS (C-ARDS), presently, no inhalable medicine containing ENXM is available. This study aims to develop a new formulation suitable for pulmonary administration of ENXM. A solution for nebulization, based on the complex between ENXM and Hydroxypropyl-β-Cyclodextrin (HPβCD) (ENXM/HPβCD) is developed. The obtained solution is characterized in terms of aerodynamic distributions and biopharmaceutical features. The evaluation of the aerosol droplets indicates a good bronchi-lung distribution of the drug. Biological evaluations of the air-liquid interface (ALI) in an in vitro lung cell model demonstrates that ENXM/HPβCD is capable of a local direct effect, increasing intracellular cyclic adenosine monophosphate (cAMP) levels and protecting from oxidative stress. This study offers a promising advance in the optimization of enoximone delivery to the lungs.

Prenatal exposure to PM2.5 led to impaired respiratory function in adult mice

BackgroundPM2.5 is a complex mixture, with water-soluble inorganic ions (WSII), mainly NH4+, SO42−, and NO3−, constituting major components. Early-life PM2.5 exposure has been shown to induce adverse health consequence but it is difficult to determine whether such an effect occurs prenatally (preconception, gestational) or postnatally in human studies. MethodsFour groups of C57BL/6 J mice were assigned to four exposure conditions: PM2.5 NO3−, PM2.5 SO42−, PM2.5 NH4+ and clean air, and exposure started at 4 weeks old. At 8 weeks old, mice bred within group. The exposure continued during gestation. After delivery, both the maternal and F1 mice (offspring) were kept in clean air without exposure to PM2.5. Respiratory function and pulmonary pathology were assessed in offspring mice at 8 weeks of age. In parallel, placenta tissue was collected for transcriptome profiling and mechanistic investigation. ResultsF1 mice in PM2.5 NH4+, SO42- and NO3− groups had 32.2 % (p=6.0e-10), 30.3 % (p=3.8e-10) and 16.9 % (p=5.7e-8) lower peak expiratory flow (PEF) than the clean air group. Importantly, the exposure-induced lung function decline was greater in male than female offspring. Moreover, exposure to PM2.5 WSII before conception and during gestation was linked to increased airway wall thickness and elevated pulmonary neutrophil and macrophage counts in the offspring mice. At the molecular level, the exposure significantly disrupted gene expression in the placenta, affecting crucial functional pathways related to sex hormone response and inflammation. ConclusionsPM2.5 WSII exposure during preconception and gestational period alone without post-natal exposure substantially impacted offspring’s respiratory function as measured at adolescent age. Our results support the paradigm of fetal origin of environmentally associated chronic lung disease and highlight sex differences in susceptibility to air pollution exposure.

Feasibility of lung lobectomy through a transdiaphragmatic approach in dogs.

Different pulmonary pathologies may require a partial or total lung lobectomy as treatment. This study compared two techniques for performing a caudal pulmonary lobectomy: a traditional lateral thoracotomy (LT) and a novel transdiaphragmatic (TD) approach. TD and LT approaches were performed on each of 18 canine cadavers. The operator and order of intervention were randomised at the beginning of the study. To compare both techniques, surgical time, percentage of area of lobe removed, incision length and iatrogenic damage were recorded. The mean length of surgery for the TD approach (1155±232.8 seconds) was non-inferior to the LT approach (1126.8±180.6 seconds) (p=0.6131). The mean percentage of the area of caudal lobe that was successfully removed during the TD approach was 25.83±8.95% (range 10.55‒40.72%) of the lobe surface, while 100% of the caudal lobe was removed during the LT approach. There was no statistical difference in iatrogenic damage between the procedures. This is a non-inferiority ex vivo study carried out by three different surgeons, and no leak test was performed after lobectomies. Partial caudal lung lobectomy can be performed in dogs by the TD approach without greater iatrogenic damage or longer surgical duration than the traditional LT approach.

A case of postpartum dermatomyositis with onset at three months: expanding the clinical spectrum

Introduction and importance: Dermatomyositis (DM) is an autoimmune disorder affecting all age groups, with a higher prevalence in women. Diagnosis typically occurs around age 40. Manifestation can be acute or chronic. Diagnosis relies on clinical, laboratory, EMG, and histopathological tests. Limited information exists regarding DM’s occurrence during pregnancy and its connection to pregnancy. Case presentation: A 31-year-old, 3-month postpartum female presented with features of proximal muscle weakness and generalized erythematous itchy rash. The weakness was associated with muscle tenderness. Laboratory evaluation and skin biopsy revealed features consistent with Dermatomyositis. Pulmonary pathology and occult tumors were investigated. Symptoms gradually improved on steroids and azathioprine. Clinical discussion: The relationship between dermatomyositis and pregnancy remains poorly understood, with only a few documented cases highlighting the impact of pregnancy on the development and progression of the disease. From the available literature, it is evident that postpartum dermatomyositis is uncommon yet significant, necessitating careful attention during pregnancy to enhance outcomes for both the mother and the unborn child. Conclusion: Our experience highlights a rare case of postpartum dermatomyositis, with symptoms emerging three months after childbirth, differing from documented cases. More research is needed to understand pregnancy’s role in dermatomyositis development and improve treatment for pregnant women with autoimmune skin diseases.

THE CHOICE OF ANESTHESIA METHOD FOR HYBRID ANGIOPLASTY. CLINICAL OBSERVATION

Many patients presenting for surgical revascularization of the lower extremities have progressive systemic atherosclerotic disease affecting not only the peripheral extremities, but also the coronary, cerebral, and renal vessels. Vascular patients are therefore considered high perioperative risk patients, making them a real challenge even for experienced anesthesiologists. This article analyzes a clinical case of hybrid angioplasty of lower extremity vessels in a patient with generalized atherosclerotic lesions under regional anesthesia with ultrasound navigation. Analysis of the clinical case and its analysis shows that regional anesthesia provides reliable protection against surgical stress with minimal impact on the body and should be used in patients with concomitant cardiac and pulmonary pathologies.

Identification of novel TTN gene variant in a patient exhibiting severe dilated cardiomyopathy co-occurring with acute fibrinoid organizing pneumonia.

Dilated cardiomyopathy (DCM) is often hereditary, with 20% to 40% of nonischemic cases showing familial linkage, yet genetic testing is underused. This report describes an unreported pathogenic nonsense variant in the Titin (TTN) gene (NM_001267550.2:c.92603G>A) in a 24-year-old man with severe DCM and acute fibrinoid organizing pneumonia, highlighting a unique cardiopulmonary pathology. We conducted detailed gross, histopathologic, immunophenotypic, and exome-based DNA sequencing analysis in the workup of this case. We also included the patient's clinical and radiologic findings in our study. With rapid clinical deterioration and complex comorbidities, including substance abuse and psychiatric conditions, which precluded transplantation, the patient's cardiac function progressively worsened. Autopsy findings included extreme cardiomegaly, biventricular hypertrophy, and acute and chronic pericarditis. Significant pulmonary pathology consistent with acute fibrinoid organizing pneumonia was also noted. Molecular testing confirmed a deleterious maternally inherited TTN variant that was absent in the sibling of the proband and the extant medical literature, highlighting its rarity and significance. This case contributes to the ongoing body of work on the impact of TTN variants on DCM. It suggests a potential link between genetic variants and complex cardiac injury patterns, emphasizing the need for further investigation into the interplay between cardiomyopathy and pulmonary pathology.