Pulmonary fibrosis (PF) is a life-threatening disorder that severely disrupts normal lung architecture and function, resulting in severe respiratory failure and death. It has no definite treatment. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has protective potential in PF. However, the mechanisms underlying these effects require further elucidation. Therefore, this study aimed to evaluate the ameliorative effect of EMPA against bleomycin (BLM)-induced PF and the potential mechanisms. Twenty-four male Wister rats were randomly divided into four groups: control, BLM treated, EMPA treated, and EMPA+BLM treated. EMPA significantly improved the histopathological injuries illustrated by both hematoxylin and eosin and Masson’s trichrome-stained lung tissue sections, as confirmed by electron microscopic examination. It significantly reduced the lung index, hydroxyproline content, and transforming growth factor β1 levels in the BLM rat model. It had an anti-inflammatory effect, as evidenced by a decrease in the inflammatory cytokines’ tumor necrosis factor alpha and high mobility group box 1, inflammatory cell infiltration into the bronchoalveolar lavage fluid, and the CD68 immunoreaction. Furthermore, EMPA mitigated oxidative stress, DNA fragmentation, ferroptosis, and endoplasmic reticulum stress, as evidenced by the up-regulation of nuclear factor erythroid 2-related factor expression, heme oxygenase-1 activity, glutathione peroxidase 4 levels, and a decrease in C/EBP homologous protein levels. This protective potential could be explained on the basis of autophagy induction via up-regulating lung sestrin2 expression and the LC3 II immunoreaction observed in this study. Our findings indicated that EMPA protected against BLM-induced PF-associated cellular stress by enhancing autophagy and modulating sestrin2/adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase 1 signaling.

Background: There is a paucity of evidence on people with thoracic aortic aneurysm and dissection. We aimed to determine the prevalence of genetic variants and their associations with phenotypes. Methods: In this cross-sectional single-centre cohort study of consecutive patients who underwent endovascular or open-surgical repair of thoracic aortic aneurysm and dissection, genetic analysis was performed using four-stage Next Generation Sequencing, and findings were confirmed with Sanger sequencing. We collected personal and family history on comorbidities, clinical examination, anthropometrics, skeletal deformities, joint function, and ophthalmological measures. Cardiovascular risk and phenotype scores were calculated. Results: Ninety-five patients were eligible (mean age 54 ± 9 years, 70% males, 56% aortic dissection). One-fifth had a family history of aortic disease. Furthermore, 95% and 54% had a phenotype score of ≤5 and ≤2, respectively. There were no significant differences in the distribution of phenotype characteristics according to age, sex, aortic pathology, or performed invasive procedures. Genetic variants of uncertain significance were detected in 40% of patients, with classic mutations comprising 18% of all variants. We observed no significant association with cardiovascular and phenotype scores but with higher joint function scores (p = 0.015). Conclusion: Genetic variants are highly present in clinically relevant aortic pathologies. Variants appear to play a larger role than previously described. The different variants do not correlate with specific phenotypes, age, pathology, sex, or family history.

Objectives: Chronic Obstructive Pulmonary Disease (COPD) is one of the most common pulmonary diseases. The concomitant association of Obstructive Sleep Apnea (OSA) and COPD is known as the Overlap Syndrome (OS). This study aimed to identify markers for predicting OS, among routine laboratory tests, including differential blood counts. Methods: One hundred twenty-five patients with exacerbated COPD were enrolled in the study and screened for OSA using the Epworth Sleepiness Scale (ESS). Those with a positive ESS score underwent polysomnography (PSG) for confirmation. All patients were followed for 90 days to monitor for subsequent exacerbations. Results: Out of the 125 patients with exacerbated COPD, 25 were confirmed to have OSA. Those with OS had a significantly higher body mass index (BMI) ( p < 0.001). The monocyte to eosinophil ratio (MER) was significantly higher in the OS group, while the neutrophil to monocyte (NMR) ratio and platelets to monocyte (PMR) ratio were significantly lower. Younger age, male sex, and higher body mass index (BMI) were all associated with OS. During the 90-day follow-up period after hospital discharge, 60% of patients with OS were re-admitted due to acute exacerbations. The hazard ratio for a second exacerbation increased by two-fold for every one-unit increase MER. The MER demonstrated excellent utility in predicting a second exacerbation, with an area under the curve (AUC) of 83% and a p-value of .005. Conclusion: The monocyte to eosinophil ratio (MER) was independent predictors of OS among exacerbated COPD patients and had a very good prognostic utility for predicting the next exacerbation episodes. Long term follow up is recommended to evaluate the severity of exacerbations and the effect of complications of OS on the morbidity and mortality of these patients.

Background: Chronic inflammation plays a crucial role in developing various cardiovascular and metabolic disorders. Obstructive sleep apnea (OSA) is a unique condition characterized by the coexistence of cardiovascular and metabolic disturbances, where chronic inflammation may exacerbate disease progression and severity. This study investigated how different hematological inflammatory cells and mediators can serve as predictive indicators of severe OSA. Methods: In a retrospective cohort study, 150 patients suspected of having obstructive sleep apnea (OSA) underwent polysomnography (PSG) to confirm the diagnosis. Based on their apnea-hypopnea index (AHI), the patients were categorized into three groups: mild, moderate, and severe OSA. Blood samples were collected for the assessment of inflammatory blood cells and mediators at the time of diagnosis. Results: Among the 150 patients studied, 90 were diagnosed with OSA, and 43 had severe OSA, representing a prevalence rate of 47.7%. Patients with severe OSA were notably older and more likely to have diabetes mellitus and hypertension. After adjusting for age and sex, each one-unit increase in Systemic Inflammatory Response Index (SIRI), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels was associated with a doubling in the likelihood of having moderate and severe OSA (p < 0.05 for all). However, hypertension was linked to a 16-fold increase in the likelihood of moderate and severe OSA (p = 0.01). Conclusion: Our research indicates that comorbidity and inflammatory cells and markers (SIRI, CRP, and ESR) are significantly related to the severity of OSA.

Background: While tuberculosis (TB) remains a significant global health threat, data on mortality in critically ill TB patients and those with drug-resistant TB (DR-TB) is limited. This study explores hematological profiles of critically ill TB patients and those with DR-TB, investigating associations with in-hospital and short-term mortality. Methods: A longitudinal study of 269 patients with confirmed TB evaluated baseline blood cell counts and indices from medical records. We calculated in-hospital mortality and short-term prognosis, followed by analysis to identify predictors of mortality using hematological parameters. Results: One-third of TB patients were critically ill (35.32%) and required intensive care unit (ICU) admission, while 14.5% had DR-TB, more common in females and smokers. Critically ill patients were older and tended to be non-smokers. DR-TB patients exhibited elevated lymphocyte and monocyte counts but lower neutrophil count and blood indices. Critically ill DS-TB patients had lower hemoglobin (Hb) and platelet (PLT) but higher total leucocytes count (TLC) and mean platelet volume (MPV). In-hospital mortality rate was 29.37%, significantly higher in critically ill DS-TB patients (74.74%). In-hospital mortality was 14-fold higher in critically ill DS-TB patients, 11-fold higher in stable DR-TB patients, and 6-fold higher in patients with comorbidities. Decreased Hb, monocyte level, and neutrophil to lymphocyte ratio (NLR) were significantly associated with in-hospital mortality. Predictors of short-term mortality included critical illness and comorbidities. However, the effect of DR-TB on short-term mortality disappeared. Decreasing Hb and TLC, especially neutrophils were significantly linked to short-term mortality. The utility of Hb in discriminating in-hospital and short-term mortality was very good, with AUC values of 78% and 79%, respectively. Cutoff values of less than 10 mg/dL and 9.75 mg/dL showed sensitivity ranging from 71 to 80% and specificity ranging from 75 to 80%, respectively. Conclusion: This study provides valuable insights into patients with DR-TB and DS-TB with critically illness. We observed elevated lymphocyte and monocyte counts in DR-TB patients, as well as significant alterations in blood indices in critically ill patients. Importantly, the in-hospital mortality was notably higher in critically ill DS-TB patients, highlighting the importance of early recognition and aggressive management in this subgroup. Specifically, certain blood parameters such as hemoglobin, monocytes, neutrophils, and the NLR were associated with an increased risk of both in-hospital and short-term mortality. Furthermore, our findings underscore the prognostic significance of hematological parameters, particularly in resource-limited settings.

Background and objectives: Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition, often complicated by frequent exacerbations and increased mortality risk. COPD patients also had a higher risk for developing diabetes mellites. Recently, the studies showed promising utility of HbA1C in identifying patients at heightened risk of critical illnesses. This study evaluated the diagnostic and prognostic value of glycated hemoglobin (HbA1c) in predicting COPD exacerbation and short-term mortality. Methods: A prospective cohort study involved 184 COPD patients. Patients were categorized as either stable or experiencing an acute exacerbation. Demographic and laboratory data, including HbA1c levels, were collected. Results: HbA1c levels were significantly elevated in COPD patients experiencing exacerbations. Factors influencing HbA1c levels included lower oxygen saturation upon admission, use of home oxygen, lymphocyte count, CRP levels, diabetes, and ischemic heart disease (IHD). HbA1c emerged as a strong predictor of both COPD exacerbation and short-term mortality. In the unadjusted model, HbA1c was associated with an increased risk of exacerbation (OR = 1.59, p = 0.001) and remained significant after adjusting for other variables (OR = 2.25, p = 0.03). Similarly, HbA1c was a significant predictor of mortality in both the unadjusted (OR = 1.44, p = 0.001) and adjusted models (OR = 1.66, p = 0.001). Notably, the use of home oxygen was associated with a lower risk of both exacerbation and mortality. Other risk factors for exacerbation included lower oxygen saturation, male sex, IHD, and a history of previous exacerbations. The mortality rate was significantly higher in patients who had experienced recent exacerbations. Conclusion: Elevated HbA1c levels were consistently associated with a higher risk of adverse outcomes, even after adjusting for other significant factors. This highlights the importance of routine HbA1c monitoring in COPD management, particularly in patients with a history of exacerbations or comorbid conditions like diabetes and ischemic heart disease. Additionally, the protective effect of home oxygen therapy against exacerbations and mortality suggests it should be considered as a key component in the management strategy for high-risk COPD patients.