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Clozapine (CLO) is a very effective antipsychotic, whose use is associated with dose-dependent risk of complications. Due to high interindividual variability in CLO metabolism, there is a need to identify factors affecting the blood concentrations of CLO and its active metabolite, norclozapine (NCLO). A total of 446 blood samples (collected from 233 women and 213 men, aged from 18 to 77 years) were included in this study and analyzed for CLO and NCLO concentrations. The patients were treated at a psychiatric hospital in Warsaw in the years 2016-2021. Serum CLO and NCLO concentrations were determined with high-performance liquid chromatography coupled to UV. The following factors were shown to increase serum CLO and NCLO levels: higher CLO dose ( < 0.001), female sex ( < 0.001), nonsmoker status ( < 0.001), the use of more than two additional psychotropic drugs (only in the case of CLO; = 0.046), concomitant use of beta-blockers (for CLO = 0.049; for NCLO < 0.001), and older age (for CLO < 0.001; for NCLO = 0.011). Despite the use of CLO at daily doses within the recommended range (200-450 mg), the evaluated serum CLO and NCLO levels were within the therapeutic ranges in only 37% and 75% of cases, respectively, with 5.6% of cases exceeding the CLO toxicity threshold. The use of CLO at recommended doses does not guarantee achieving therapeutic concentrations of CLO or NCLO. Women and nonsmokers were at the highest risk of having toxic CLO levels.

Due to its exceptional effectiveness, clozapine (CLO), whose metabolite is norclozapine (NCLO), is a drug of choice in the management of treatment-resistant schizophrenia. The purpose of this study was to assess the factors modifying the CLO/NCLO ratio (CNR). A total of 446 blood samples (233 of which were drawn from females and 213 from males, aged from 18 to 77 years) were analyzed in this study. The patients were treated at a psychiatric hospital in the period 2016-2021. Serum CLO and NCLO levels were determined with high-performance liquid chromatography coupled with a UV detector. The median CNR was 2.38 (minimum 0.30, maximum 14.36). Our analysis showed that neither sex (p= 0.135) nor smoking ( = 0.774) had any significant effect on the CNR. However, increased doses of CLO resulted in lower CNR values ( = 0.005). Concomitant use of other psychotropic drugs increased the CNR ( = 0.001). The results of our study indicate a need for personalized CLO treatment. Assessing the CNR may be useful in identifying CLO interaction with other psychotropic drugs.

IntroductionClozapine (CLO) remains the gold standard for the treatment of drug-resistant schizophrenia. It is commonly accepted that there is a linear relationship between CLO dose and blood concentration, although deviations from this pattern are frequently observed in clinical practice. The aim of the present naturalistic study was to further investigate this relationship using a real-world database of CLO therapeutic drug monitoring (TDM) samples, with a particular focus on: i) identifying cases of “unexpected” CLO levels during repeated within-subject blood sampling in the process of CLO dose adjustment and ii) assessing linearity of the cross-sectional, between-subject CLO dose-concentration relationship and identifying potential breakpoints.MethodsThe study was based on a single-center TDM database derived from routine monitoring of CLO concentration in psychiatric inpatients, supplemented with data from medical records. The database was reviewed independently by a laboratory medicine specialist and psychiatrist to identify individual cases of “unanticipated” dose-concentration relationships. The study also employed the Multivariate Adaptive Regression Splines (MARS) to detect non-linear relationships in the prediction of CLO levels, as determined by high-performance liquid chromatography. Analyses incorporated variables such as daily CLO dose, smoking status, age, sex, and co-medications.ResultsIndividual cases of “unanticipated” CLO concentrations supporting the partially non-linear within-subject dose-concentration relationship were unambiguously identified by both specialists. The MARS model revealed a breakdown in the between-subject CLO dose-concentration linear relationship identifying a hinge point around 400 mg/day, below which CLO concentrations were less dose-dependent. CLO dose and smoking were the most important predictive factors, but the model explained only about 25% of CLO concentration variability.ConclusionOur data suggest that the non-linear relationship between CLO concentration and its daily dose can be a real-life clinical problem with CLO doses of ∼400 mg/day as the provisional hinge point. Although preliminary, the present results warrant further investigations on non-linear aspects of CLO pharmacology, including “unexpected” CLO concentrations, toxicity, and lack of therapeutic activity.

Between Heaven and Hell: Roman Kołakowski’s Poetry and His Translations of The Tiger Lillies Songs of The Tiger Lillies, a “punk cabaret” group from London, entered the Polish- speaking culture mostly through the translations by Roman Kołakowski. Translation formed just one of many fields of artistic activity of Kołakowski, who was also a poet, a songwriter, a performer, and a theatre director. There exists, however, a striking contrast between the style of the Kołakowski’s own oeuvre and his translation choices. His poetry is mostly religious, patriotic, marked by a solemn tone and elevated register, while The Tiger Lillies delight in ridicule, irony, and perversion, mocking religion in an almost blasphemous way. The paper is an attempt at analysing this contrast and searching for its assumed sources. The target texts are found to be marked by significant semantic and stylistic modifications when compared to the original songs. Amplification of religious tropes and of negative views on modern society is identified as the main form of the translator’s interventions. Based on the comparison of Kołakowski’s translations with his own poetry, it is posited that their ostensible discrepancy may be explained by perceiving the translations as a subsidiary field of artistic expression, where the translator pursues his interests in grimmer aspects of morality and society, expressing them in a form that would not be coherent with his own poetry. Consequently, Kołakowski’s translations of The Tiger Lillies’ songs are considered appropriations in a sense that the translational choices are directed by the translator’s own interests, ideological stance, and sensibilities, rather than by any attempted equivalence with the source texts. It is to be hoped that the paper will form an in itation to further investigations of translational agency in the field of song translation.

Songs of The Tiger Lillies, a “punk cabaret” group from London, entered the Polish- speaking culture mostly through the translations by Roman Kołakowski. Translation formed just one of many fields of artistic activity of Kołakowski, who was also a poet, a songwriter, a performer, and a theatre director. There exists, however, a striking contrast between the style of the Kołakowski’s own oeuvre and his translation choices. His poetry is mostly religious, patriotic, marked by a solemn tone and elevated register, while The Tiger Lillies delight in ridicule, irony, and perversion, mocking religion in an almost blasphemous way. The paper is an attempt at analysing this contrast and searching for its assumed sources. The target texts are found to be marked by significant semantic and stylistic modifications when compared to the original songs. Amplification of religious tropes and of negative views on modern society is identified as the main form of the translator’s interventions. Based on the comparison of Kołakowski’s translations with his own poetry, it is posited that their ostensible discrepancy may be explained by perceiving the translations as a subsidiary field of artistic expression, where the translator pursues his interests in grimmer aspects of morality and society, expressing them in a form that would not be coherent with his own poetry. Consequently, Kołakowski’s translations of The Tiger Lillies’ songs are considered appropriations in a sense that the translational choices are directed by the translator’s own interests, ideological stance, and sensibilities, rather than by any attempted equivalence with the source texts. It is to be hoped that the paper will form an in itation to further investigations of translational agency in the field of song translation.

Songs of The Tiger Lillies, a \"punk cabaret\" group from London, entered the Polish-speaking culture mostly through the translations by Roman Kołakowski. Translation formed just one of many fields of artistic activity of Kołakowski, who was also a poet, a songwriter, a performer, and a theatre director. There exists, however, a striking contrast between the style of the Kołakowski's own oeuvre and his translation choices. His poetry is mostly religious, patriotic, marked by a solemn tone and elevated register, while The Tiger Lillies delight in ridicule, irony, and perversion, mocking religion in an almost blasphemous way. The paper is an attempt at analysing this contrast and searching for its assumed sources. The target texts are found to be marked by significant semantic and stylistic modifications when compared to the original songs. Amplification of religious tropes and of negative views on modern society is identified as the main form of the translator's interventions. Based on the comparison of Kołakowski's translations with his own poetry, it is posited that their ostensible discrepancy may be explained by perceiving the translations as a subsidiary field of artistic expression, where the translator pursues his interests in grimmer aspects of morality and society, expressing them in a form that would not be coherent with his own poetry. Consequently, Kołakowski's translations of The Tiger Lillies' songs are considered appropriations in a sense that the translational choices are directed by the translator's own interests, ideological stance, and sensibilities, rather than by any attempted equivalence with the source texts. It is to be hoped that the paper will form an invitation to further investigations of translational agency in the field of song translation.

The aim of the study was to evaluate factors that may contribute to the persistence of positive, negative and other psychopathological symptoms of schizophrenia. All patients were treated in general psychiatric wards between January 2006 and December 2017. The initial study sample comprised of the medical reports of 600 patients. The main, specified inclusion criterion for the study was schizophrenia as a discharge diagnosis. Medical reports of 262 patients were excluded from the study due to no neuroimaging scans being available. The symptoms were categorised into three groups: positive, negative, and other psychopathological symptoms. The statistical analysis comprised modalities such as demographic data, clinical symptoms, as well as neuroimaging scans linking them to a potential impact of sustaining the mentioned groups of symptoms during the period of hospitalization. The analysis revealed that statistically significant risk factors of persistence of the three groups of symptoms are the elderly age, the increasing toll of hospitalizations, suicidal attempts in medical history, a family history of alcohol abuse, the presence of positive, negative and other psychopathological symptoms on admission to the hospital, as well as the absence of cavum septi pellucidi (CSP). The study showed that addiction to psychotropic drugs and a family history of schizophrenia were more frequent in patients with persistent CSP.

The number of cases of pancreatic cancers in 2019 in Poland was 3852 (approx. 2% of all cancers). The course of the disease is very fast, and the average survival time from the diagnosis is 6 months. Only <2% of patients live for 5 years from the diagnosis, 8% live for 2 years, and almost half live for only about 3 months. A family predisposition to pancreatic cancer occurs in about 10% of cases. Several oncogenes in which somatic changes lead to the development of tumours, including genes BRCA1/2 and PALB2, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1, are involved in pancreatic cancer. Between 4% and 10% of individuals with pancreatic cancer will have a mutation in one of these genes. Six percent of patients with pancreatic cancer have NTRK pathogenic fusion. The pathogenesis of pancreatic cancer can in many cases be characterised by homologous recombination deficiency (HRD)—cell inability to effectively repair DNA. It is estimated that from 24% to as many as 44% of pancreatic cancers show HRD. The most common cause of HRD are inactivating mutations in the genes regulating this DNA repair system, mainly BRCA1 and BRCA2, but also PALB2, RAD51C and several dozen others.

Background: Substance use is a growing problem worldwide, and there is a great need to develop national policies addressing prevention and treatment of substance-use disorders (SUD). However, the lack of a commonly used, valuable diagnostic tool to assess the symptoms of SUDs precludes comparison of the prevalence of drug-use problems as well as the efficacy of policy strategies applied in different countries. This study was conducted to validate one of the commonly used scales the Drug Use Disorders Identification Test (the DUDIT) for use in Polish condition. Objectives: The aims of this study were to test the reliability of the DUDIT in the Polish population, to confirm the comparative stability of the factor structure of the instrument, and to verify previously proposed DUDIT cutoff scoring. Methods: The group of drug users comprised 127 patients aged 19–40 years (mean age 30.37, SD 6.36) with a diagnosis of SUD, while the control group consisted of 533 students aged 19–25 years (mean age 20.72, SD 1.88). All participants completed the Polish version of the DUDIT. Internal consistency of the Polish version of the DUDIT was determined, and subsequently external validation was performed. Results: Analysis showed that the Polish version of the DUDIT was characterized by a good reliability based on Cronbach’s α, with a value of 0.92. The between-group comparison revealed a significant difference between the control group and substance-dependent patients corresponding to a large effect size (Cohen’s d = 3.27). The receiver-operating characteristic analysis, comparing the DUDIT score to the ICD-10 diagnosis of SUD, showed an optimal cutoff value of 7 points, with a sensitivity of 0.929 and a specificity of 0.974. Conclusion: These results constitute preliminary evidence that the Polish version of the DUDIT may be a valid and reliable screening tool for drug-use disorders in the Polish population.

Animal studies using tests and models have demonstrated that magnesium exerts an antidepressant effect. The literature contains few studies in humans involving attempts to augment antidepressant therapy with magnesium ions. The purpose of our study was to assess the efficacy and safety of antidepressant treatment, in combination with magnesium ions. A total of 37 participants with recurrent depressive disorder who developed a depressive episode were included in this study. As part of this double-blind study, treatment with the antidepressant fluoxetine was accompanied with either magnesium ions (120 mg/day as magnesium aspartate) or placebo. During an 8-week treatment period, each patient was monitored for any clinical abnormalities. Moreover, serum fluoxetine and magnesium levels were measured, and pharmaco-electroencephalography was performed. The fluoxetine + magnesium and fluoxetine + placebo groups showed no significant differences in either Hamilton Depression Rating Scale (HDRS) scores or serum magnesium levels at any stage of treatment. Multivariate statistical analysis of the whole investigated group showed that the following parameters increased the odds of effective treatment: lower baseline HDRS scores, female gender, smoking, and treatment augmentation with magnesium. The parameters that increased the odds of remission were lower baseline HDRS scores, shorter history of disease, the presence of antidepressant-induced changes in the pharmaco-EEG profile at 6 h after treatment, and the fact of receiving treatment augmented with magnesium ions. The limitation of this study is a small sample size.