Clinical Hematochemical Parameters in Differential Diagnosis between Pediatric SARS-CoV-2 and Influenza Virus Infection: An Automated Machine Learning Approach.

BACKGROUND: The influenza virus and the novel beta coronavirus (SARS-CoV-2) have similar transmission characteristics, and it is very difficult to distinguish them clinically. With the development of information technologies, novel opportunities have arisen for the application of intelligent software systems in disease diagnosis and patient triage. METHODS: A cross-sectional study was conducted on 268 infants: 133 infants with a SARS-CoV-2 infection and 135 infants with an influenza virus infection. In total, 10 hematochemical variables were used to construct an automated machine learning model. RESULTS: An accuracy range from 53.8% to 60.7% was obtained by applying support vector machine, random forest, k-nearest neighbors, logistic regression, and neural network models. Alternatively, an automated model convincingly outperformed other models with an accuracy of 98.4%. The proposed automated algorithm recommended a random tree model, a randomization-based ensemble method, as the most appropriate for the given dataset. CONCLUSIONS: The application of automated machine learning in clinical practice can contribute to more objective, accurate, and rapid diagnosis of SARS-CoV-2 and influenza virus infections in children.

Hemogram-based decision tree models for discriminating COVID-19 from RSV in infants.

OBJECTIVE: Decision trees are efficient and reliable decision-making algorithms, and medicine has reached its peak of interest in these methods during the current pandemic. Herein, we reported several decision tree algorithms for a rapid discrimination between coronavirus disease (COVID-19) and respiratory syncytial virus (RSV) infection in infants. METHODS: A cross-sectional study was conducted on 77 infants: 33 infants with novel betacoronavirus (SARS-CoV-2) infection and 44 infants with RSV infection. In total, 23 hemogram-based instances were used to construct the decision tree models via 10-fold cross-validation method. RESULTS: The Random forest model showed the highest accuracy (81.8%), while in terms of sensitivity (72.7%), specificity (88.6%), positive predictive value (82.8%), and negative predictive value (81.3%), the optimized forest model was the most superior one. CONCLUSION: Random forest and optimized forest models might have significant clinical applications, helping to speed up decision-making when SARS-CoV-2 and RSV are suspected, prior to molecular genome sequencing and/or antigen testing.

Prognostic Role of Monocyte Distribution Width, CRP, Procalcitonin and Lactate as Sepsis Biomarkers in Critically Ill COVID-19 Patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic and one group of patients has developed a severe form of COVID-19 pneumonia with an urgent need for hospitalization and intensive care unit (ICU) admission. The aim of our study was to evaluate the prognostic role of MDW, CRP, procalcitonin (PCT), and lactate in critically ill COVID-19 patients. The primary outcome of interest is the 28 day mortality of ICU patients with confirmed SARS-CoV-2 infection and sepsis (according to Sepsis 3 criteria with acute change in SOFA score ≥ 2 points). Patients were divided into two groups according to survival on the 28th day after admission to the ICU. Every group was divided into two subgroups (women and men). Nonparametric tests (Mann-Whitney) for variables age, PCT, lactate, and MDW were lower than alpha p < 0.05, so there was a significant difference between survived and deceased patients. The Chi-square test confirmed statistically significant higher values of MDW and lactate in the non-survivor group. We found a significant association between MDW, lactate, procalcitonin, and fatal outcome, higher values were reported in the deceased group.

Could platelet indices have diagnostic properties in children with COVID-19?

INTRODUCTION: Viral infections are often accompanied by reactive thrombocytosis, that is, increased activity of platelets, which is especially common in infants and children. OBJECTIVE: This study aimed to test the diagnostic properties of platelet indices, plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW), in children with beta corona virus 2 (SARS-CoV-2) infection. METHODS: The study included 232 patients below the age of 18 admitted to the coronavirus disease (COVID-19) isolation wards at the Institute for Child and Youth Health Care of Vojvodina. PCT, MPV and PDW values on the day of admission were recorded. In total, 245 controls were selected from those treated for SARS-CoV-2 negative respiratory infections. Descriptive and inferential statistical analyses were performed. RESULTS: MPV and PDW were found important as independent predictors for COVID-19 in children. Furthermore, the joint effect of MPV and PDW for predicting COVID-19 was confirmed. The parameters showed better sensitivity than specificity. CONCLUSION: Our study showed that PCT is not clinically significant, while MPV and PDW have diagnostic value in predicting COVID-19 in children. In perspective, these parameters could be implemented in the various learning algorithms in order to achieve earlier diagnosis and treatment.

The Effect of Humidity on the Dissolution Kinetics and Tablet Properties of Immediate-Release Tablet Formulation Containing Lamotrigine.

This study aims to find the effects of high (75%) and low (30%) humidity conditions and its correlation with formulation composition on dissolution kinetics of lamotrigine (LMT) from prepared immediate-release tablets during one- and four-week periods. Two types of fillers microcrystalline cellulose (MCC) or anhydrous lactose (LAC), disintegrant sodium starch glycolate (NaSG, 0.5% or 4%), and lubricant magnesium stearate (MgST, 0.25% or 5%) were used. A three-factor two-stage complete factorial design (23) was used to assess the influence of the composition of the tested formulations. The tablets were produced by direct compression and characterized using a disintegration test, a resistance to crushing test, and dissolution tests (pH 1.2 and pH 6.8). Using Design Expert software, it was concluded that in addition to the effect of fillers on pH 6.8, NaSG has a significant impact after exposure to high and low humidity, as well as its interaction with LAC and MCC. In the dissolution medium pH 1.2, under conditions of high humidity, the content of MgST and NaSG and their interaction show a significant influence. The release rate of LMT was affected by humidity as well as type of excipients and their interactions.

Immortelle essential oil-based ointment improves wound healing in a diabetic rat model.

The phytochemical analysis of the investigated Immortelle essential oil revealed the presence of monoterpenes and sesquiterpenes as major components that might be efficient as a wound healing potential agent. The present study aimed to develop an ointment based on the Immortelle essential oil and investigate its wound healing effects on excision wounds in diabetic rats. The topical formulated Immortelle ointment was subjected to pharmaco-technical characterization. Thirty-two diabetic rats with the induced excision wound were used to evaluate in vivo wound healing effects of ointment. The animals were randomly divided into four groups untreated or topically treated with either a 1% silver sulfadiazine, the ointment base, or Immortelle ointment. The response to the treatment was assessed by macroscopic, biochemical and histopathological analysis. The ointment, compatible with the skin remained stable for 6 months. Topical application of the Immortelle ointment showed the highest wound contraction with the highest content of hydroxyproline in comparison to the all examined groups. The Immortelle ointment showed significant wound contraction from day 7 to day 21 as compared to other groups. On the day 21, there was an average of 99.32% wound contraction in the Immortelle group, whereas the mean wound contraction in the negative control and ointment base group was 71.36% and 81.26% respectively. The histopathological results validated the potential wound healing effect of Immortelle ointment with evident post-excision scar maturation and increased collagen fibers density. Our findings revealed that the Immortelle ointment approach might serve as a promising and innovative tool for wound healing.

Association Between the Inflammatory Biomarkers and Left Ventricular Systolic Dysfunction in Patients with Exacerbations of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Cardiovascular diseases are an important cause of morbidity and mortality in chronic obstructive pulmonary disease patients. The increased inflammatory biomarker levels predict exacerbations and are associated with cardiovascular diseases in stable chronic obstructive pulmonary disease patients but their role in the settings of acute chronic obstructive pulmonary disease exacerbations has not been determined. AIMS: To analyse the association between inflammatory biomarkers and heart failure and also to determine the predictors of mortality in patients with exacerbations of chronic obstructive pulmonary disease. STUDY DESIGN: Prospective observational study. METHODS: We analysed 194 patients admitted for acute exacerbation of chronic obstructive pulmonary disease at The Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia. In all patients, C-reactive protein, fibrinogen, N-terminal of the pro-hormone brain natriuretic peptide and white blood count were measured and transthoracic echocardiography was performed. RESULTS: There were 119 men (61.3%) and the median age was 69 years (interquartile range 62-74). Left ventricular systolic dysfunction (ejection fraction <50%) was present in 47 (24.2%) subjects. Patients with left ventricular systolic dysfunction had higher C-reactive protein levels (median 100 vs. 31 mg/L, p=0.001) and fibrinogen (median 5 vs. 4 g/L, p=<0.001) compared to those with preserved ejection fraction. The overall hospital mortality was 8.2% (16/178). The levels of C-reactive protein, fibrinogen, N-terminal pro-brain natriuretic peptide and ejection fraction predicted hospital mortality in univariate analysis. After adjusting for age, hypoxemia and C-reactive protein, ejection fraction remained significant predictors of hospital mortality (OR 3.89, 95% CI 1.05-15.8). CONCLUSION: Nearly a quarter of patients with the exacerbation of chronic obstructive pulmonary disease present with left ventricular systolic dysfunction which may be associated with mortality.

Confidence level in venipuncture and knowledge on causes of in vitro hemolysis among healthcare professionals.

INTRODUCTION: This study aimed to assess confidence level of healthcare professionals in venipuncture and their knowledge on the possible causes of in vitro hemolysis. MATERIALS AND METHODS: A sample of 94 healthcare professionals (nurses and laboratory technicians) participated in this survey study. A four-section questionnaire was used as a research instrument comprising general information for research participants, knowledge on possible causes of in vitro hemolysis due to type of material used and venipuncture technique and specimen handling, as well as assessment of healthcare professionals' confidence level in their own ability to perform first and last venipuncture. RESULTS: The average score on the knowledge test was higher in nurses' than in laboratory technicians (8.11±1.7, and 7.4±1.5, respectively). The difference in average scores was statistically significant (P=0.035) and Cohen's d in the range of 0.4 indicates that there is a moderate difference on the knowledge test among the health care workers. Only 11/94 of healthcare professionals recognized that blood sample collection from cannula and evacuated tube is method which contributes most to the occurrence of in vitro hemolysis, whereas most risk factors affecting occurrence of in vitro hemolysis during venipuncture were recognized. There were no significant differences in mean score on the knowledge test in relation to the confidence level in venipuncture (P=0.551). CONCLUSION: Confidence level at last venipuncture among both profiles of healthcare staff was very high, but they showed insufficient knowledge about possible factors affecting hemolysis due to materials used in venipuncture compared with factors due to venipuncture technique and handling of blood sample.

Interleukin-6 and procalcitonin as biomarkers in mortality prediction of hospitalized patients with community acquired pneumonia.

INTRODUCTION: Community acquired pneumonia (CAP) may present as life-threatening infection with uncertain progression and outcome of treatment. Primary aim of the trial was determination of the cut-off value of serum interleukin-6 (IL-6) and procalcitonin (PCT) above which, 30-day mortality in hospitalized patients with CAP, could be predicted with high sensitivity and specificity. We investigated correlation between serum levels of IL-6 and PCT at admission and available scoring systems of CAP (pneumonia severity index-PSI, modified early warning score-MEWS and (Confusion, Urea nitrogen, respiratory rate, Blood pressure, ≥65 years of age-CURB65). METHODS: This was prospective, non-randomized trial which included 101 patients with diagnosed CAP. PSI, MEWS and CURB65 were assessed on first day of hospitalization. IL-6 and PCT were also sampled on the first day of hospitalization. RESULTS: Based on ROC curve analysis (AUC ± SE = 0.934 ± 0.035; 95%CI(0.864-1.0); P = 0.000) hospitalized CAP patients with elevated IL-6 level have 93.4% higher risk level for lethal outcome. Cut-off value of 20.2 pg/ml IL-6 shows sensitivity of 84% and specificity of 87% in mortality prediction. ROC curve analysis confirmed significant role of procalcitonin as a mortality predictor in CAP patients (AUC ± SE = 0.667 ± 0.062; 95%CI(0.546-0.789); P = 0.012). Patients with elevated PCT level have 66.7% higher risk level for lethal outcome. As a predictor of mortality at the cut-off value of 2.56 ng/ml PCT shows sensitivity of 76% and specificity of 61.8%. CONCLUSIONS: Both IL-6 and PCI are significant for prediction of 30-day mortality in hospitalized patients with CAP. Serum levels of IL6 correlate with major CAP scoring systems.

Relation of functional characteristics and serum alpha-1-antitrypsin (AAT) concentration in patients with PiMM phenotype and chronic obstructive pulmonary disease (COPD).

INTRODUCTION: The relation of AAT phenotype and COPD still raises lots of controversy. In this study we aimed to investigate relation lung function characteristics, AAT serum level and COPD in smoking and non smoking population. PATIENTS AND METHODS: This was a prospective non-randomized study in which we evaluated 45 patients with severe (stage IV) COPD. In all patients we determined AAT phenotype, serum AAT levels and lung function tests. We correlated findings in relation to the smoking status. RESULTS: All patients were MM type homozygotes. Serum AAT concentrations were within the reference values, amounting to 1.66g/l in smokers and 1.80g/l in nonsmokers. There was no significant correlation between serum AAT concentrations and lung function parameters. We have observed the higher mean values of ITGV, RV, TLC and RV/TLC in smokers and a statistically significant difference only in ITGV. CONCLUSION: All of the investigated patients with severe COPD were MM type homozygotes with normal plasma level of AAT. There was no significant correlation between the phenotype and severity of COPD. We did not find significant relation of plasma AAT level and lung function impairment.

[Treatment effects of co-amoxiclav (Amoxiclav 2x) in acute exacerbation of severe chronic obstructive pulmonary disease: clinical evaluation].

INTRODUCTION: The exacerbation of chronic obstructive pulmonary disease is most often induced by an infection of bacterial origin in over 50% of the cases (or mixed bacterial and viral infection). This study was aimed at evaluating clinical effects of antibiotics co-amoxiclav. Amoxiicillin with clavulanic acid in the treatment of patients with severe chronic obstructive pulmonary disease exacerbation. MATERIAL AND METHODS: The investigation included 38 patients with severe chronic obstructive pulmonary disease exacerbation hospitalized at the Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica. The patients were randomly selected for the antibiotic treatment with Amoxiclav twice a day in 12 hour intervals. The clinical effects of the applied treatment were evaluated by analyzing certain laboratory findings, microbiological sputum findings and improvement of subjective symptoms. RESULTS: Of the examined subjects, 65% were males and 35% were females, their mean age being 66.4 +/- 8.86, and who were mostly smokers (73%). After the completion Of Applied antibiotic treatment, a significant reduction and normalization of all inflammation markers were recorded, as well as a significant improvement of the patients' subjective symptoms. The positive microbiological sputum findings (Haemophilus influenzae, Pseudomonas aeruginosa and Streptococcus pneumoniae) were recorded in 13.58% of the patients. The bacterial agent was eradicated on the third day of the applied treatment. The mean length of the treatment was 7.07 +/- 0.91 days, with no undesirable treatment side effects observed CONCLUSION The antibiotic therapy is justifiable as the initial treatment regimen of severe chronic obstructive pulmonary disease exacerbation and amoxicillin with clavulanic acid is reported as the first-line antibiotic drug in most pharmacotherapy guidelines.

Clinical trials in advanced stage lung cancer: a survey of patients' opinion about their treatment.

BACKGROUND: The major aim of this study was to investigate what patients with advanced stage lung cancer, enrolled in a clinical trial, thought about their treatment. We also wanted to investigate if there exist any characteristics that could influence patients' opinion about the clinical trial. PATIENTS AND METHODS: Over the period from June 2008 to June 2009, 59 eligible patients were enrolled in this study. The major inclusion criteria were: participation in a clinical trial, previously treated advanced stage lung cancer, and good performance status (ECOG 0-2). All patients were asked to answer a questionnaire designed to investigate their impressions about participation in a clinical trial. The questionnaire was deposited in a sealed box which was opened at the end of the study.We investigated a possible influence of age, gender, education, lung cancer stage, chemotherapy line and tumor type on the patients' opinion about some aspects of the clinical trial. RESULTS: The majority of the patients were aware they were participating in the clinical trial and a significant number of them were very satisfied with the treatment. Of the investigated factors, only the level of education had a statistically significant influence on some of the questions raised in the questionnaire. CONCLUSIONS: Patients participating in clinical trials are satisfied with their treatment, ready to proceed with it and would recommend it to other patients. It depends mainly on health professionals to maintain this level of confidence and justify their trust.

Characteristics of novel myeloid precursor cell line, PC-MDS, established from a bone marrow of the patient with therapy-related myelodysplastic syndrome.

We report on characteristics of the first human cell line, PC-MDS, derived from a bone marrow of a patient with therapy-related myelodysplastic syndrome (t-MDS) who had no overt post-MDS leukemia. Classic cytology analyses, immunophenotyping, cytogenetic and molecular genetic procedures were used for characterization of the cell line. PC-MDS cells are positive for the expression of CD13, CD15, CD30, CD33, and CD45 antigen. Positive cytochemical staining and immunophenotype analyses indicated that PC-MDS cells have some characteristics of the early myeloid precursor cell. The karyotype analysis of PC-MDS cell line revealed various numerical and structural changes including those typically associated with t-MDS: del(5)(q13)[7], der(5)t(5;11)(p11;q11)[13], -7[6], del(7)(q31)[2], +20[3], -20[4]. Evaluation of methylation status in a promoter region of p15, p16 and MGMT genes showed biallelic hypermethylation pattern of 5' promoter region only in MGMT gene. PC-MDS is the first t-MDS derived cell line, and based on its immunological, cytogenetic and molecular characterization could be a new tool in evaluation of complex biology of MDS and a model for methylation studies.