Balkan Medical Journal最新文献

Background: In the postacute phase of coronavirus disease-2019 (COVID-19), survivors may have persistent symptoms, lung function abnormalities, and sequelae lesions on thoracic computed tomography (CT). This new entity has been defined as post-COVID interstitial lung disease (ILD) or residual disease.

Aims: To evaluate the characteristics, risk factors and clinical significance of post-COVID ILD.

Study design: Multicenter cross-sectional analysis of data from a randomized clinical study.

Methods: In this study, patients with persistent respiratory symptoms 3 months after recovery from COVID-19 were evaluated by two pulmonologists and a radiologist. post-COVID ILD was defined as the presence of respiratory symptoms, hypoxemia, restrictive defect on lung function tests, and interstitial changes on follow-up high-resolution computed tomography (HRCT).

Results: At the three-month follow-up, 375 patients with post-COVID-19 syndrome were evaluated, and 262 patients were found to have post-COVID ILD. The most prevalent complaints were dyspnea (n = 238, 90.8%), exercise intolerance (n = 166, 63.4%), fatigue (n = 142, 54.2%), and cough (n = 136, 52%). The mean Medical Research Council dyspnea score was 2.1 ± 0.9, oxygen saturation was 92.2 ± 5.9%, and 6-minute walking distance was 360 ± 140 meters. The mean diffusing capacity of the lung for carbon monoxide was 58 ± 21, and the forced vital capacity was 70% ± 19%. Ground glass opacities and fibrotic bands were the most common findings on thoracic HRCT. Fibrosis-like lesions such as interlobular septal thickening and traction bronchiectasis were observed in 38.3% and 27.9% of the patients, respectively. No honeycomb cysts were observed. Active smoking [odds ratio (OR), 1.96; 95% confidence interval (CI), 1.44-2.67), intensive care unit admission during the acute phase (OR, 1.46; 95% CI, 1.1-1.95), need for high-flow nasal oxygen (OR, 1.55; 95% CI, 1.42-1.9) or non-invasive ventilation (OR, 1.31; 95% CI, 0.8-2.07), and elevated serum lactate dehydrogenase levels (OR, 1.23; 95% CI 1.18-1.28) were associated with the development of post-COVID ILD. At the 6-month follow-up, the respiratory symptoms and pulmonary functions had improved spontaneously without any specific treatment in 35 patients (13.4%). The radiological interstitial lesions had spontaneously regressed in 54 patients (20.6%).

Conclusion: The co-existence of respiratory symptoms, radiological parenchymal lesions, and pulmonary functional abnormalities which suggest a restrictive ventilatory defect should be defined as post-COVID-19 ILD. However, the term “fibrosis” should be used carefully. Active smoking, severe COVID-19, and elevated lactate dehydrogenase level are the main risk factors of this condition. These post-COVID functional and radiological changes could disappear over time in 20% of the patients.

Background: Zinc (Zn), an essential micronutrient, regulates and maintains neurological functions. However, both Zn deficiency and excess can cause oxidative stress and neurodegenerative diseases. As previously reported, immunoglobulin G (IgG) can modulate oxidative stress in various disorders.

Aims: To investigate whether IgG treatment can alleviate oxidative stress caused by Zn⁰ on microglia in vitro.

Study design: In vitro study.

Methods: The feasibility of Zn⁰ treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn⁰, either alone or with IgG supplementation, was determined with dihydrorhodamine 123 staining. Flow cytometry was employed to ascertain the intracellular protein levels of TRIM21, PINK, PARKIN, MFN2, Beclin-1, and active LC3B.

Methods: The feasibility of Zn⁰ treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn⁰, either alone or with IgG supplementation, was determined with dihydrorhodamine 123 staining. Flow cytometry was employed to ascertain the intracellular protein levels of TRIM21, PINK, PARKIN, MFN2, Beclin-1, and active LC3B. Results: In silico screening confirmed the association between Zn⁰ cytotoxicity and apoptosis. Furthermore, oxidative stress was identified as a critical mechanism that underlies Zn⁰ neurotoxicity. The in silico analysis revealed that Zn can interact with the constant region of the Ig heavy chain, suggesting a potential role for IgG in alleviating Zn⁰-induced cytotoxicity. Experimental findings supported this hypothesis, as IgG administration significantly reduced Zn⁰-induced mitochondrial stress in a dose-dependent manner. The upregulation of PINK1 levels by Zn⁰ exposure suggests that mitochondrial injury promotes mitophagy. Interestingly, Zn⁰ decreased TRIM21 levels, which is reversed by IgG administration.

Conclusion: These findings elucidate the cellular responses to Zn⁰ and highlight the potential use of intravenous immunoglobulin in mitigating the adverse effects of acute Zn⁰ exposure.

In recent decades, the prevalence of inborn errors of immunity has increased, necessitating the development of more effective treatment and care options for these highly morbid conditions. Due to these “experiments of nature,” the complicated nature of the immune system is being revealed. Based on the functional and molecular tests, targeted therapies are now being developed which offer a more effective approach and reduce damage. This study aimed to investigate a key cytokine of the cellular immune response, interferon‐gamma (IFN-γ), which is linked to Mendelian susceptibility to Mycobacterial disease, and its potential as a therapeutic option for IFN-γ deficiency.

Background: Allergen-specific immunotherapy, a unique inducer of tolerance, may result in T cell exhaution.

Aims: To investigate how the duration of house dust mite (HDM) subcutaneous immunotherapy (SCIT) affects the expression of major immune checkpoint (ICP) molecules on the surface of CD4⁺ T-helper and regulatory T (Treg) cells.

Study design: Cross-sectional study.

Methods: We enrolled 28 children with HDM-induced allergic rhinitis (AR) and six controls. The study participants were divided into six groups: one group each of patients in their first, second, and third years of HDM-SCIT; one group each comprising those in the first year following HDM-SCIT and those on pharmacotherapy; and the control group. The expression of ICPs on CD4⁺ T and Treg cells was determined using flow cytometry, and plasma levels of soluble ICPs were estimated by ELISA.

Results: Our results revealed a significant increase in the expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and lymphocyte activation gene 3 (LAG-3) on CD4⁺ T cells during the second and third years of SCIT, respectively. Additionally, a strong correlation was observed between the expression of CTLA-4 and T cell immunoglobulin and mucin domain containing molecule-3 in CD4⁺ T cells. Furthermore, we observed a significant correlation between the expressions of programmed cell death protein-1, CTLA-4, T cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Motif domain, and LAG-3 on both CD4⁺ T and Treg cells. A robust correlation was observed between the plasma levels of soluble ICPs.

Conclusion: HDM-SCIT induces CD4⁺ T cell exhaution, which may contribute to tolerance induction in children with AR.