Endotyping Eosinophilic Inflammation in COPD with ELAVL1, ZfP36 and HNRNPD mRNA Genes.

Background: Chronic obstructive pulmonary disease (COPD) is a common disease characterized by progressive airflow obstruction, influenced by genetic and environmental factors. Eosinophils have been implicated in COPD pathogenesis, prompting the categorization into eosinophilic and non-eosinophilic endotypes. This study explores the association between eosinophilic inflammation and mRNA expression of ELAVL1, ZfP36, and HNRNPD genes, which encode HuR, TTP and AUF-1 proteins, respectively. Additionally, it investigates the expression of IL-9 and IL-33 in COPD patients with distinct eosinophilic profiles. Understanding these molecular associations could offer insights into COPD heterogeneity and provide potential therapeutic targets. Methods: We investigated 50 COPD patients, of whom 21 had eosinophilic inflammation and 29 had non-eosinophilic inflammation. Epidemiological data, comorbidities, and pulmonary function tests were recorded. Peripheral blood mononuclear cells were isolated for mRNA analysis of ELAVL1, ZfP36, and HNRNPD genes and serum cytokines (IL-9, IL-33) were measured using ELISA kits. Results: The study comprised 50 participants, with 66% being male and a mean age of 68 years (SD: 8.9 years). Analysis of ELAVL1 gene expression revealed a 0.45-fold increase in non-eosinophilic and a 3.93-fold increase in eosinophilic inflammation (p = 0.11). For the ZfP36 gene, expression was 6.19-fold higher in non-eosinophilic and 119.4-fold higher in eosinophilic groups (p = 0.07). Similarly, HNRNPD gene expression was 0.23-fold higher in non-eosinophilic and 0.72-fold higher in eosinophilic inflammation (p = 0.06). Furthermore, serum levels of IL-9 showed no statistically significant difference between the eosinophilic and non-eosinophilic group (58.03 pg/mL vs. 52.55 pg/mL, p = 0.98). Additionally, there was no significant difference in IL-33 serum levels between COPD patients with eosinophilic inflammation and those with non-eosinophilic inflammation (39.61 pg/mL vs. 37.94 pg/mL, p = 0.72). Conclusions: The data suggest a notable trend, lacking statistical significance, towards higher mRNA expression for the ZfP36 and HNRNPD genes for COPD patients with eosinophilic inflammation compared to those with non-eosinophilic inflammation.

Patients Hospitalized for COVID-19 in the Periods of Delta and Omicron Variant Dominance in Greece: Determinants of Severity and Mortality.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been a pandemic since 2020, and depending on the SARS-CoV-2 mutation, different pandemic waves have been observed. The aim of this study was to compare the baseline characteristics of patients in two phases of the pandemic and evaluate possible predictors of mortality. METHODS: This is a retrospective multicenter observational study that included patients with COVID-19 in 4 different centers in Greece. Patients were divided into two groups depending on the period during which they were infected during the Delta and Omicron variant predominance. RESULTS: A total of 979 patients (433 Delta, 546 Omicron) were included in the study (median age 67 years (54, 81); 452 [46.2%] female). Compared to the Omicron period, the patients during the Delta period were younger (median age [IQR] 65 [51, 77] vs. 70 [55, 83] years, p < 0.001) and required a longer duration of hospitalization (8 [6, 13] vs. 7 [5, 12] days, p = 0.001), had higher procalcitonin levels (ng/mL): 0.08 [0.05, 0.17] vs. 0.06 [0.02, 0.16], p = 0.005, ferritin levels (ng/mL): 301 [159, 644] vs. 239 [128, 473], p = 0.002, C- reactive protein levels (mg/L): 40.4 [16.7, 98.5] vs. 31.8 [11.9, 81.7], p = 0.003, and lactate dehydrogenase levels (U/L): 277 [221, 375] vs. 255 [205, 329], p < 0.001. The Charlson Comorbidity Index was lower (3 [0, 5] vs. 4 [1, 6], p < 0.001), and the extent of disease on computed tomography (CT) was greater during the Delta wave (p < 0.001). No evidence of a difference in risk of death or admission to the intensive care unit was found between the two groups. Age, cardiovascular events, acute kidney injury during hospitalization, extent of disease on chest CT, D-dimer, and neutrophil/lymphocyte ratio values were identified as independent predictors of mortality for patients in the Delta period. Cardiovascular events and acute liver injury during hospitalization and the PaO2/FiO2 ratio on admission were identified as independent predictors of mortality for patients in the Omicron period. CONCLUSIONS: In the Omicron wave, patients were older with a higher number of comorbidities, but patients with the Delta variant had more severe disease and a longer duration of hospitalization.

The Role of Minocycline in the Treatment of Nosocomial Infections Caused by Multidrug, Extensively Drug and Pandrug Resistant Acinetobacter baumannii: A Systematic Review of Clinical Evidence.

Treatment options for multidrug resistant Acinetobacter baumannii strains (MDR-AB) are limited. Minocycline has been used alone or in combination in the treatment of infections associated with AB. A systematic review of the clinical use of minocycline in nosocomial infections associated with MDR-AB was performed according to the PRISMA-P guidelines. PubMed-Medline, Scopus and Web of Science TM databases were searched from their inception until March 2019. Additional Google Scholar free searches were performed. Out of 2990 articles, 10 clinical studies (9 retrospective case series and 1 prospective single center trial) met the eligibility criteria. In total, 223 out of 268 (83.2%) evaluated patients received a minocycline-based regimen; and 200 out of 218 (91.7%) patients with available data received minocycline as part of a combination antimicrobial regimen (most frequently colistin or carbapenems). Pneumonia was the most common infection type in the 268 cases (80.6% with 50.4% ventilator-associated pneumonia). The clinical and microbiological success rates following minocycline treatment were 72.6% and 60.2%, respectively. Mortality was 20.9% among 167 patients with relevant data. In this systematic review, minocycline demonstrated promising activity against MDR-AB isolates. This review sets the ground for further studies exploring the role of minocycline in the treatment of MDR-AB associated infections.