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Objectives. Defining precisely the normal range of HE4 protein is crucial for the proper interpretation of tumor marker results and for a more efficient diagnosis of ovarian malignancy. The aim of our study was to evaluate a reference limit of HE4 protein in a population to promote and facilitate the common use of HE4 protein assays. We also tried to identify potential association of HE4 levels with other conditions such as smoking, age, BMI, and creatinine levels. Methods. Blood samples were collected from 617 patients divided into three groups: healthy, pregnant, and with benign ovarian tumors. Serum HE4 concentrations were measured following a standard procedure. HE4 reference ranges for each group and association of HE4 levels with BMI, creatinine, and smoking were investigated. Results. HE4 reference limit for healthy patients equals 85 pmol/l, which becomes 73 pmol/l and 93 pmol/l for pre and postmenopausal subgroups, respectively. There is a statistically significant correlation between HE4 serum level and smoking (p=0.000001) and there is no correlation with creatinine. But if we take into account age and smoking, in multivariate analysis, there is a correlation. For pregnant, the upper limit values of normal HE4 levels are 55 pmol/l (median=40 pmol/l), 80 pmol/l (median=43 pmol/l), and 106 pmol/l (median=53 pmol/l) for the first, second, and third trimesters, respectively. Conclusions. HE4 protein value strongly depends on the patient’s age and smoking. The serum concentration of HE4 marker increases with the duration of pregnancy. Understanding the normal range of HE4 protein enables the correct interpretation of marker measurements. This may result in an earlier and more effective diagnosis of ovarian cancer.

Arterial hypertension is considered to be an inflammatory condition with low intensity. Therefore, an elevated concentration of inflammatory cytokines can be expected in patients with systemic arterial hypertension, including tumor necrosis factor (TNF). The study included a group of 96 persons aged 18 to 65 years: 76 patients with primary arterial hypertension and 20 healthy individuals (control group). Blood pressure was measured in all individuals using the office and ambulatory blood pressure monitoring (ABPM) measurement, blood was collected for laboratory tests [tumor necrosis factor (TNF), tumor necrosis factor receptor 1 (TNFR1)], and 24-hour urine collection was performed in which albuminuria and TNF concentration were assessed. Moreover, assessment of the intima-media thickness (IMT) in ultrasonography and left ventricular mass index (LVMI) in echocardiography were carried out. Statistically elevated TNF concentration in the blood serum ( P = .0001) and in the 24-hour urine collection ( P = .0087) was determined in patients with hypertension in comparison with the control group. The TNF and TNFR1 concentration in the serum and TNF in the 24-hour urine in the group of patients with arterial hypertension and organ damages and without such complications did not differ statistically significantly. We observed a positive and statistically significant correlation between TNFR1 concentration in the serum and TNF urine excretion in patients with hypertension ( r = 0.369, P < .05) Patients with arterial hypertension are characterized by higher TNF concentrations in blood serum and higher TNF excretion in 24-hour urine than healthy persons. TNF and TNFR1 concentration in blood serum and TNF excretion in 24-hour urine in patients with early organ damages due to arterial hypertension do not differ significantly from those parameters in patients with arterial hypertension without organ complications. There is a positive correlation between TNFR1 concentration in the serum and TNF urine excretion in patients with hypertension.

Multiple choice questions (MCQs) are commonly used for assessing students, but medical teachers may lack training in writing them. MCQs often have imperfections called item-writing flaws (IWFs) that can affect students’ results and impede objective evaluation of their knowledge. This study aimed to evaluate a guideline-based faculty development intervention on writing MCQs at Levels 1 and 2 of the Kirkpatrick Model. MCQs written by teachers prior and after the intervention were analyzed with the Shapiro–Wilk test, Student’s t-test, and Wilcoxon signed-rank test as appropriate. In addition, the phenomenological approach was chosen to describe experiences of 10 teachers in semi-structured in-depth interviews. Results showed satisfaction of teachers with the document. They found it helpful in writing MCQs and noticed the requirement for another guidelines. They appreciated it for its briefness and clarity. The statistical analysis of the quality of MCQs before and after the intervention showed that the document contributed to a statistically significant reduction of IWFs. To conclude, our results showed that a guideline document on writing MCQs may serve as a well-received and effective faculty development intervention. The document may be used as a flexible, time-saving, and just-in-time learning method, fitting needs of medical teachers.

While the use of statins in treating patients with atherosclerosis is an undisputed success, the questions regarding an optimal starting time for treatment and its strength remain open. We proposed in our earlier paper published in Int. J. Mol. Sci. (2019, 20) that the growth of intima-media thickness of the carotid artery follows an S-shape (i.e., logistic) curve. In our subsequent paper in PLoS ONE (2020, 15), we incorporated this feature into a logistic control-theoretic model of atherosclerosis progression and showed that some combinations of patient age and intima-media thickness are better suited than others to start treatment. In this study, we perform a new and comprehensive calibration of our logistic model using a recent clinical database. This allows us to propose a procedure for inferring an optimal age to start statin treatment for a particular group of patients. We argue that a decrease in the slope of the IMT logistic growth curve, induced by statin treatment, is most efficient where the curve is at its steepest, whereby the efficiency means lowering the future IMT levels. Using the procedure on an aggregate group of severely sick men, 38 years of age is observed to correlate with the steepest point of the logistic curve, and, thus, it is the preferred time to start statin treatment. We believe that detecting the logistic curve’s steepest fragment and commencing statin administration on that fragment are courses of action that agree with clinician intuition and may support decision-making processes.