Developing Prediction Models for COVID-19 Outcomes: A Valuable Tool for Resource-Limited Hospitals.

Purpose: Coronavirus disease is a global pandemic with millions of confirmed cases and hundreds of thousands of deaths worldwide that continues to create a significant burden on the healthcare systems. The aim of this study was to determine the patient clinical and paraclinical profiles that associate with COVID-19 unfavourable outcome and generate a prediction model that could separate between high-risk and low-risk groups. Patients and Methods: The present study is a multivariate observational retrospective study. A total of 483 patients, residents of the municipality of Timișoara, the biggest city in the Western Region of Romania, were included in the study group that was further divided into 3 sub-groups in accordance with the disease severity form. Results: Increased age (cOR=1.09, 95% CI: 1.06-1.11, p<0.001), cardiovascular diseases (cOR=3.37, 95% CI: 1.96-6.08, p<0.001), renal disease (cOR=4.26, 95% CI: 2.13-8.52, p<0.001), and neurological disorder (cOR=5.46, 95% CI: 2.71-11.01, p<0.001) were all independently significantly correlated with an unfavourable outcome in the study group. The severe form increases the risk of an unfavourable outcome 19.59 times (95% CI: 11.57-34.10, p<0.001), while older age remains an independent risk factor even when disease severity is included in the statistical model. An unfavourable outcome was positively associated with increased values for the following paraclinical parameters: white blood count (WBC; cOR=1.10, 95% CI: 1.05-1.15, p<0.001), absolute neutrophil count (ANC; cOR=1.15, 95% CI: 1.09-1.21, p<0.001) and C-reactive protein (CRP; cOR=1.007, 95% CI: 1.004-1.009, p<0.001). The best prediction model including age, ANC and CRP achieved a receiver operating characteristic (ROC) curve with the area under the curve (AUC) = 0.845 (95% CI: 0.813-0.877, p<0.001); cut-off value = 0.12; sensitivity = 72.3%; specificity = 83.9%. Conclusion: This model and risk profiling may contribute to a more precise allocation of limited healthcare resources in a clinical setup and can guide the development of strategies for disease management.

Environmental Factors Influencing the Dynamics and Evolution of COVID-19: A Systematic Review on the Study of Short-Term Ozone Exposure.

The potential influence of environmental factors, particularly air pollutants such as ozone (O3), on the dynamics and progression of COVID-19 remains a significant concern. This study aimed to systematically review and analyze the current body of literature to assess the impact of short-term ozone exposure on COVID-19 transmission dynamics and disease evolution. A rigorous systematic review was conducted in March 2023, covering studies from January 2020 to January 2023 found in PubMed, Web of Science, and Scopus. We followed the PRISMA guidelines and PROSPERO criteria, focusing exclusively on the effects of short-term ozone exposure on COVID-19. The literature search was restricted to English-language journal articles, with the inclusion and exclusion criteria strictly adhered to. Out of 4674 identified studies, 18 fulfilled the inclusion criteria, conducted across eight countries. The findings showed a varied association between short-term ozone exposure and COVID-19 incidence, severity, and mortality. Some studies reported a higher association between ozone exposure and incidence in institutional settings (OR: 1.06, 95% CI: 1.00-1.13) compared to the general population (OR: 1.00, 95% CI: 0.98-1.03). The present research identified a positive association between ozone exposure and both total and active COVID-19 cases as well as related deaths (coefficient for cases: 0.214; for recoveries: 0.216; for active cases: 0.467; for deaths: 0.215). Other studies also found positive associations between ozone levels and COVID-19 cases and deaths, while fewer reports identified a negative association between ozone exposure and COVID-19 incidence (coefficient: -0.187) and mortality (coefficient: -0.215). Conversely, some studies found no significant association between ozone exposure and COVID-19, suggesting a complex and potentially region-specific relationship. The relationship between short-term ozone exposure and COVID-19 dynamics is complex and multifaceted, indicating both positive and negative associations. These variations are possibly due to demographic and regional factors. Further research is necessary to bridge current knowledge gaps, especially considering the potential influence of short-term O3 exposure on COVID-19 outcomes and the broader implications on public health policy and preventive strategies during pandemics.

Betulin complex in γ-cyclodextrin derivatives: properties and antineoplasic activities in in vitro and in vivo tumor models.

Given the present high incidence of melanoma and skin cancer, interest in potential drugs of plant origin has increased significantly. Pentacyclic lupane-type triterpenes are widely distributed in plants, offering numerous pharmacological benefits. Betulin is an important compound in the bark of Betula pendula Roth and has important therapeutic properties, including antitumor activities. Its biological effect is limited by its poor water solubility, which can be improved by cyclodextrin complexation. The best results have been obtained by using a novel cyclodextrin derivative, octakis-[6-deoxy-6-(2-sulfanyl ethanesulfonate)]-γ-CD. The complexes between betulin and the previously mentioned cyclodextrin were analyzed by scanning electron microscopy (SEM)and differential scanning calorimetry (DSC) and pharmacologically evaluated in vitro (MTT and immunocytochemistry tests) and in vivo in C57BL/6J mice. The solubility of betulin is improved by cyclodextrin complexation, which creates a stable complex that improves the in vitro and in vivo properties of the active compound.

Increased serum IL-17 is an independent risk factor for severe asthma.

BACKGROUND: IL-17 expression was found to be associated with many inflammatory diseases in humans, such as rheumatoid arthritis, asthma, systemic lupus erythematosus and allograft rejection and many in vitro studies have indicated a proinflammatory function for IL-17. OBJECTIVE: Prognostic value of increased serum IL-17 in asthma patients. METHODS: Serum IL-17 (ELISA) was measured in 85 asthma patients (pts), mean age 46.99 +/- 14.1 years, 61% females, 23 mild persistent, 26 moderate persistent and 36 severe persistent asthma. Using multiple regression analysis (STATISTICA 7), increased serum IL-17 (>20 pg/ml) was tested as risk factor for severe asthma in comparison with "traditional" risk factors: smoke, NSAID intolerance, obesity, chronic rhinosinusitis, blood eosinophilia, FEV(1) at baseline < 50% predicted (low FEV(1)). RESULTS: Medium serum IL-17 values were 14.21 pg/ml in mild asthma, 12.22 pg/ml in moderate asthma and 24.72 pg/ml in severe asthma. IL-17 values > 20 pg/ml were encountered in 3(13%) mild asthma pts (p < 0.001 vs. severe asthma), 2(8%) moderate asthma pts. (p < 0.001 vs. severe asthma), and in 11(31%) severe asthma pts. For severe asthma multiple regression analysis revealed as independent risk factors IL-17 (p = 0.000290), NSAID intolerance (p = 0.000585) and low FEV(1) (p = 0.000059). CONCLUSIONS: IL-17 is increased in severe asthma compared to mild/moderate forms of the disease and values above 20 pg/ml are an independent risk factor for severe asthma.

Estrogen receptor alpha polymorphisms and the risk of malignancies.

Estrogens represent risk factors for endocrine-related cancers and play also an important role in the development and progression of other malignancies. In order to analyze the associations between estrogen receptor gene alpha polymorphisms and cancers susceptibility, we genotyped six single nucleotide polymorphisms (SNPs) in 163 Caucasian cancer patients--103 breast cancers and 60 other malignancies (colorectal, bladder, hepatocellular carcinoma and acute myeloid leukemia)--and 114 healthy controls using hybridization probes. We performed Armitage`s association trend-test to evaluate the risk. Linkage disequilibrium (LD) was assessed for each pair of markers. The genotypes CC and CT of rs3798577 were significantly associated with the cancers risk (p-trend breast = 4 × 10(-5); p-trend cancers = 1 × 10(-5)); in discrepancy with breast cancer where the C-allele represented the risk allele, for bladder, hepatocellular carcinomas and leukemia, the T allele seems to confer susceptibility. The minor G allele of rs1801132 was protective in our cases (p = 1 × 10(-4)); for rs2228480, the heterozygous frequency was higher for cancer groups (p = 0.03); the SNP pairs rs2228480&rs3798577 and rs2234693&rs9340799 were in low LD; the haplotypes T-A of rs2234693&rs9340799 and G-C of rs2228480&rs3798577 showed a trend to be higher represented in breast cancers; T allele of rs2234693 was higher expressed in breast, colon cancers and leukemia; rs2077647 was associated with colon (p = 0.008, C-risk allele) and bladder (p = 0.01, T-risk allele) cancers. We concluded that ESR1 polymorphisms may have distinct impact in carcinogenesis and further genotyping will establish whether these findings remain significant in larger cohorts.

Antinuclear antibodies in asthma patients- a special asthma phenotype?

Several studies reported the appearance of asthma and autoimmune conditions in the same patient, but the clinical significance of this association was not yet assessed. One hundred asthmatic patients were observed for one year evolution with death, severe exacerbations, intake of > 1000 micrograms of beclometasone or equivalent (high ICS) and FEV1 decline >100 ml, in relation with ANA (ELISA), sputum and blood eosinophilia (EO), NSAID intolerance, BMI >25, chronic rhinosinusitis, smoking status and FEV1 <30% predicted (low FEV1). After 1 year of observation, there were 5 deaths, 28 severe asthma exacerbations requiring hospitalisations, 24 cases requiring high inhaled corticosteroid intake, and 19 patients with fast FEV1 decline (>100 ml/year). Multiple regression analysis pointed out several different independent risk factors for severe asthma evolution: for death presence of ANA (P=0.037), NSAID intolerance (P<0.001) and low FEV1 (P=0.021); for evolution with severe exacerbations ANA (p=0.011), sputum EO (P<0.001), smoking (P=0.044) and NSAID intolerance (P=0.022); for high ICS intake ANA (P=0.036), sputum EO (P=0.026) and low FEV1 (P=0.006); for FEV1 decline >100 ml ANA (P=0.006), sputum EO (P=0.037), BMI>25 (P=0.046) and NSAID intolerance (P=0.017). The presence of ANA is an independent risk factor in asthma for evolution with death, severe exacerbations, high inhaled corticosteroid intake and FEV1 decline >100 ml.