Immunophenotypes of anti-SARS-CoV-2 responses associated with fatal COVID-19.

Background: The relationship between anti-SARS-CoV-2 humoral immune response, pathogenic inflammation, lymphocytes and fatal COVID-19 is poorly understood. Methods: A longitudinal prospective cohort of hospitalised patients with COVID-19 (n=254) was followed up to 35 days after admission (median, 8 days). We measured early anti-SARS-CoV-2 S1 antibody IgG levels and dynamic (698 samples) of quantitative circulating T-, B- and natural killer lymphocyte subsets and serum interleukin-6 (IL-6) response. We used machine learning to identify patterns of the immune response and related these patterns to the primary outcome of 28-day mortality in analyses adjusted for clinical severity factors. Results: Overall, 45 (18%) patients died within 28 days after hospitalisation. We identified six clusters representing discrete anti-SARS-CoV-2 immunophenotypes. Clusters differed considerably in COVID-19 survival. Two clusters, the anti-S1-IgGlowestTlowestBlowestNKmodIL-6mod, and the anti-S1-IgGhighTlowBmodNKmodIL-6highest had a high risk of fatal COVID-19 (HR 3.36-21.69; 95% CI 1.51-163.61 and HR 8.39-10.79; 95% CI 1.20-82.67; p≤0.03, respectively). The anti-S1-IgGhighestTlowestBmodNKmodIL-6mod and anti-S1-IgGlowThighestBhighestNKhighestIL-6low cluster were associated with moderate risk of mortality. In contrast, two clusters the anti-S1-IgGhighThighBmodNKmodIL-6low and anti-S1-IgGhighestThighestBhighNKhighIL-6lowest clusters were characterised by a very low risk of mortality. Conclusions: By employing unsupervised machine learning we identified multiple anti-SARS-CoV-2 immune response clusters and observed major differences in COVID-19 mortality between these clusters. Two discrete immune pathways may lead to fatal COVID-19. One is driven by impaired or delayed antiviral humoral immunity, independently of hyper-inflammation, and the other may arise through excessive IL-6-mediated host inflammation response, independently of the protective humoral response. Those observations could be explored further for application in clinical practice.

Real-world outcomes, treatment patterns and T790M testing rates in non-small cell lung cancer patients treated with first-line first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors from the Slovenian cohort of the REFLECT study.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective treatments for EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC). However, routine clinical practice is different between countries/institutions. PATIENTS AND METHODS: The REFLECT study (NCT04031898) is a retrospective medical chart review that explored real-life treatment and outcomes of EGFRm NSCLC patients receiving first-line (1L) first-/second-generation (1G/2G) EGFR TKIs in 8 countries. This study included adult patients with documented advanced/metastatic EGFRm NSCLC with 1L 1G/2G EGFR TKIs initiated between Jan 2015 - Jun 2018. We reviewed data on clinical characteristics, treatments, EGFR/T790M testing patterns, and survival outcomes. Here, we report data from 120 medical charts in 3 study sites from Slovenia. RESULTS: The Slovenian cohort (median age 70 years, 74% females) received 37% erlotinib, 32% afatinib, 31% gefitinib. At the time of data collection, 94 (78%) discontinuations of 1L TKI, and 89 (74%) progression events on 1L treatment were reported. Among patients progressing on 1L, 73 (82%) were tested for T790M mutation yielding 50 (68%) positive results, and 62 (85%) received 2L treatment. 82% of patients received osimertinib. Attrition rate between 1L and 2L was 10%. The median (95% CI) real-world progression free survival on 1L EGFR TKIs was 15.6 (12.6, 19.2) months; median overall survival (95% CI) was 28.9 (25.0, 34.3) months. CONCLUSIONS: This real-world study provides valuable information about 1G/2G EGFR TKIs treatment outcomes and attrition rates in Slovenian EGFRm NSCLC patients. The reduced attrition rate and improved survival outcomes emphasize the importance of 1L treatment decision.

Decolorization and mineralization of reactive dyes, by the H2O2/UV process with electrochemically produced H2O2.

Decolorization of Reactive Red 238, Reactive Orange 16, Reactive Black 5 and Reactive Blue 4 was studied in the UV/H2O2 process with H2O2 being produced electrochemically. The experimental results show that decolorization increased considerably when switching on the electrochemical production of H2O2. Complete decolorization (>99%) was achieved for all dyes under the applied experimental conditions, partial mineralization (49-85%) was obtained, which depends on the type of dye. Reactive Red 238 was used to investigate operational parameters and it was found that decolorization was influenced by the applied electrical current of the electrochemical cell and flow rate. Decolorization and mineralization of Reactive Red 238 can be described by pseudo-first order kinetics. It was found that the initial concentration of Reactive Red 238 has a negative influence on the pseudo-first order reaction constant.

Multivariate analysis and chemometric characterisation of textile wastewater streams.

The aim of this work was to design a quick and reliable method for the evaluation and classification of wastewater streams into treatable and non-treatable effluents for reuse/recycling. Different chemometric methods were used for this purpose handling the enormous amount of data, and additionally to find any hidden information, which would increase our knowledge and improve the classification. The data obtained from the processes description, together with the analytical results of measured parameters' characterising the wastewater of a particular process, enabled us to build a fast-decision model for separating different textile wastewater outlets. Altogether 49 wastewater samples from the textile finishing company were analysed, and 19 different physical chemical measurements were performed for each of them. The resulting classification model was aimed at an automated decision about the choice of treatment technologies or a prediction about the reusability of wastewaters within any textile finishing or other company having similar characteristics of wastewater streams.

Body mass index and prognosis in patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Nutritional status, weight loss and cachexia have important prognostic implications in patients with chronic obstructive pulmonary disease (COPD). Body mass index (BMI) has been implicated in COPD risk assessment, but information is mostly limited to composite scores or to patients with stable disease. We aimed to analyse the association between BMI and mortality in acute exacerbation of COPD. METHODS: This retrospective survey included 968 patients hospitalized due to acute exacerbation of COPD at the University Clinic Golnik from February 2002 to June 2007. Vital status was ascertained with Central Population Registry, and database was censored on November 1, 2008. RESULTS: Median BMI was 25.08 kg/m(2) (interquartile range, 21.55-29.05 kg/m(2)) and 210 patients (22%) had BMI < 21 kg/m(2). During median follow-up of 3.26 years (1.79-4.76 years), 430 patients (44%) died. Lowest mortality was found for BMI 25.09-29.05 kg/m(2). When divided per BMI decile, mortality was lowest for BMI 25.09-26.56 kg/m(2) (33%). In univariate analysis, BMI per quartile and BMI per unit increase were predictive for all-cause mortality. In an adjusted model, BMI per 1 kg/m(2) unit increase was associated with 5% less chance of death (hazard ratio 0.95, 95% confidence interval 0.93-0.97). CONCLUSIONS: Low BMI < 21 kg/m(2) is frequent in patients hospitalized due to acute exacerbation of COPD. Higher BMI was independently predictive of better long-term survival. A better outcome in obese patients compared to normal weight is in contrast to primary prevention data but concurs with observations of an obesity paradox in other cardiovascular diseases.

Adherence to treatment guidelines and long-term survival in hospitalized patients with chronic obstructive pulmonary disease.

RATIONALE AND AIMS: Adherence to treatment guidelines in chronic obstructive pulmonary disease (COPD) has been shown to be less than optimal over the COPD continuum. This retrospective study aimed to assess the implementation of COPD guidelines and potential association with long-term mortality in patients with COPD. METHODS: All consecutive patient discharges in the period of February 2002-June 2007 from the University Clinic of Pulmonary and Allergic Diseases Golnik, Slovenia, were screened for a primary discharge diagnosis of COPD. RESULTS: Data on 1185 patients (mean age 70 ± 9 years, 72% men, 64% GOLD stage III/IV) were analysed. In the discharge letters 62% of patients had three or more drugs prescribed; 3% had no regular prescription. Most patients were discharged with short-acting (91%) and long-acting ß2-agonists (LABAs, 65%) and inhaled corticosteroids (61%), and 23% received long-term oxygen therapy. Prescription rates of LABAs, tiotropium and inhaled corticosteroids increased over the disease continuum (P < 0.001). In total, 48% of patients died during a median follow-up of 1149 days. Deceased patients had been less often treated with LABAs, inhaled corticosteroids and tiotropium. In multivariate Cox proportional-hazards analysis, advanced age, current smoking status, lower body mass index, longer hospital stay and cancer were associated with higher mortality (P < 0.05 for all), and inhaled corticosteroids predicted lower mortality (hazard ratio 0.72, 95% confidence interval 0.55-0.94). CONCLUSION: Implementation of guideline-recommended therapy was not optimal, particularly in patients who died during follow-up. The high long-term mortality calls for careful risk assessment and appropriate adherence to treatment guidelines.