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Lung cancer is statistically the most common disorder both in Poland and in the world. It has poor prognosis and a high degree of mortality. According to WHO, it is the sixth cause of deaths among all diseases and the first one in cancer-related deaths. At the onset of the 21st century the molecular biology began exploring more closely metabolic pathways of a tumor and specific genetic mutations were recognized. This has led to the introduction of new molecules after many years of using standard chemotherapy. The first breaking point was development of tyrosine kinase inhibitors for patients with detected EGFR, EML4-ALK or ROS1 mutations. Another important group was immune checkpoint inhibitors, which pembrolizumab is one of representatives. It is a monoclonal antibody that blocks the PD-1/PD-L1 pathway. Under physiological conditions PD-1 plays an important role in regulating cytotoxic T cells activity. It is responsible for their activation, proliferation and secretion. The PD-1/PD-L1 interaction subsides immune responses and promotes self‐tolerance through suppressing T cells activity. It is considered to be a protection against autoimmune response. Studies on the tumor microenvironment have shown that tumor cells are able to use the above described mechanism to escape from the host immune surveillance by expressing PD‐L1, which negatively regulates immune responses by interacting with PD‐1 receptor on T cells. These reports prompted scientists to create monoclonal antibodies that block the PD-1/PD-L1 axis leading to the approval of several drugs that have proven effective in treating a wide variety of cancers, including non-small cell lung cancer (NSCLC). Pembrolizumab gained first FDA approval in 2016. Initially it covered second-line monotherapy treatment of PD-L1 positive advanced NSCLC. However, the approval has been quickly broadened to include patients with PD-L1 expression ≥50% in the first-line setting. Many outcomes of randomized controlled trials regarding the use of pembrolizumab yielded an expansion of its registration in almost every histological subtype of NSCLC. Immunotherapy with pembrolizumab shows a reasonable safety and tolerability profile. The most serious side effects include thyroid dysfunction, autoimmune pneumonia and skin problems. The more common side effects such as fatigue, nausea and diarrhea are mild and usually do not contribute to discontinuation of treatment.

Background. Properly managed immunosuppression in post-transplant therapy is a necessary for minimizing the risk of organ rejection. Aim of the study. Steady-state tacrolimus (TAC) trough concentration (Cssmin) analysis in the first month following heart or kidney transplantation. The intra-individual coefficient of variation (CV) was calculated, correlations with biochemical parameters were searched and recommendations/current guidelines for optimizing TAC dosing based on evidence-based medical databases (EBM) were presented. Material and methods. 24 patients aged 24-79 years (mean 47,1±13,9 years) were selected for retrospective analysis; 12 after heart transplant and 12 after kidney transplant. TAC dosing was the same in the patient groups and did not change during the analysis (first month); in heart recipients it was 2 mg/day and 1 mg/day in kidney recipients. Whole blood Cssmin TAC (steady state) was measured four times in all patients; the first in the 15th day of treatment, the second in 16-18, the third in 17-19, the fourth in 18-21. The QMS Tacrolimus immunoassay was used to analyze TAC concentration using the Indiko Plus automated chemistry analyzer. Results. The median Cssmin TAC value was 6,9-15,6 ng/mL after heart transplant and 8,7-16,0 ng/mL after kidney transplant. The CV range of patients after heart transplantation was 4-60%, while after kidney transplantation it was 8-40%. CV>30% (a higher risk of acute rejection) after heart transplant concerned 25% of patients and 15% after kidney transplant. The analysis of organ survival in heart and kidney recipients showed 83% and 100%, respectively, at an average of 2,7±0,5 and 3,25±2,5 years after transplantation. There were no significant correlations (p>0,05) between CV and selected biochemical parameters. Conclusion. CV>30% may indicate a large variability in the pharmacokinetics of TAC and thus, the need to optimize the dosage/physiological parameters affecting its concentration values. It seems necessary to improve the personalization of immunosuppressive therapy with TAC, taking into account individual parameters of extra- and intra-individual variability, in order to obtain better therapeutic results and avoid acute/chronic rejection, accelerated in time of organ transplant loss and/or the occurrence of additional side effects of TAC.

Subject of research Therapy drug monitoring under the control of valproic acid (VPA) is now a well-established tool for the treatment of epilepsy. The pharmacokinetic variability of VPA and inter-individual differences in epilepsy type/seizure severity depending on patients’ age determine serum concentration of this drug in an individual patient. The application of the "individual therapeutic concentration" may be a useful indicator taking into account the clinical condition of a patient. Aim. The aim was to compare values of stationary VPA concentrations in terms of dosing and clinical effect monitoring in different age of epileptic patients. Methods Thirty-three patients at age 20-70 years were divided into three groups: I 20-25 years (n = 15), II 26-39 years (n = 9), III 40-70 years (n = 9). Nine patients were treated with VPA in monotherapy, others received VPA with at least one antiepileptic drug (n = 24). Plasma VPA Cssmin were measured, at steady state, using the commercial CEDIA® Valproic Acid II Assay. Results VPA Cssmin values in groups I, II and III were within the therapeutic range: 93%, 56% and 30%; above it: 0%, 33% and 55% and below it: 6%, 22% and 0%, respectively. The percentage of patients with the least frequent seizure was highest in group I (60%) compared to II (54%) and III (44%). The highest frequency of seizures was in group III (25 seizures/week) compared to group I (6.5 seizures/week). The percentage of patients with 1 attack in 1-7 days was comparable in groups: I (13%), II (12%) and III (12%). On the other hand, the percentage of patients free from epileptic seizures (> 1 year) was the highest in group I (53%) compared to group II (44%) and III (22%). Conclusions The reasons for the obtained differences could be drug interactions, nutritional style and the lack of compliance. The unpredictable VPA dose-concentration-clinical effect supports the need to optimize the therapy and define "individual therapeutic concentration". Using it in practice along with patient’s individual indications and clinical condition allows to achieve seizure-free period with good tolerance or optimal seizure control with minimal VPA side-effects.

Alopecia as a disease condition can be a symptom of other ailments, the body’s reaction to medications, hormonal changes, nutritional deficiencies, hygiene negligence, too intense or frequent cosmetic procedures, or it can constitute an independent disease syndrome. Depending on the individual genetic traits, alopecia may also be inherited. Usually, there is no one universal cause for this disease to occur. Properly conducted diagnosis of the problem and individually selected therapeutic substances can help to deal with this problem or at least delay hair loss associated with the physiological aging process. One of the treatments that are used to support the treatment or prevention of alopecia is needle mesotherapy. It is a local treatment that delivers healing substances having stimulating, regenerating, and nourishing effects directly to the skin or hair follicles. The medicinal substances administered during the needle mesotherapy treatment include peptides, biotin, minoxidil, d-panthenol, vitamins, and minerals, alone or in the form of mixtures, as well as platelet-rich plasma and stem cells. The effects of needle mesotherapy in alopecia are visible after a single treatment when hair loss stops. On the other hand, the thickening and regrowth of new hair are visible after a series of treatments. The full course of therapy depends on the type of alopecia, a patient’s condition, and its comorbidities. It usually consists of four to eight treatments performed at two-week intervals. In the case of alopecia, they are visible after two months, and to maintain the effect, a reminder treatment is recommended after six months. Not all people can undergo such a procedure. The main contraindications include: (1) pregnant and lactating women; (2) children and persons under the age of 18; (3) people who are allergic to any of the ingredients of the administered preparation; (4) people with skin lesions, skin diseases, active infections (bacterial, viral, fungal) or susceptibility to streptococcal infections (recurrent strep throat); (5) people taking drugs: immunosuppressants, anticoagulants, non-steroidal anti-inflammatory drugs, high doses of glucocorticosteroids; (6) patients with decompensated diabetes, neoplastic, mental, rheumatic diseases, or other autoimmune disorders. Needle mesotherapy is very popular in cosmetology and aesthetic medicine clinics. This innovative method is a proven and relatively safe procedure in the fight against various skin conditions, including alopecia. Keywords: excessive hair loss, alopecia, needle mesotherapy, platelet-rich plasma, biomimetic peptides, stem cells.

The anticonvulsant properties of valproic acid (VPA), a branched short-chain fatty acid, were serendipitously discovered in 1963. Since then, therapeutic roles of VPA have increased to include bipolar disorder and migraine prophylaxis, and have more recently been proposed in cancer, Alzheimer's disease, and HIV treatment. Overall, most patients with epilepsy are optimally treated with serum VPA concentrations of 50–100 mg/l. The unpredictable relationship between dose and VPA concentration supports the need to individualize and maintain therapy using therapeutic drug monitoring (TDM). TDM has been used as a tool to optimize treatment of epilepsy for almost 50 years, and while VPA evidence for its usefulness in improving clinical outcome is scarce, TDM continues to play a role in epilepsy management for reasons: (1)physiological changes due to aging, pregnancy, nutritional status, drug interactions, and comorbidities (ie, those involving liver and kidney function) can affect the pharmacokinetics of this drug; (2)treatment is prophylactic and seizures may occur at irregular intervals; (3)signs of toxicity may be insidious and difficult to interpret, especially if there is associated mental handicap or treatment with multiple antiepileptic drugs (AEDs). The chronic, sometimes lifelong therapy makes it particularly important to monitor treatment to reduce long-term adverse effects. These arguments for TDM are valid regardless of the AED involved. This article discusses the basic pharmacokinetic characteristics of conventional anti-epileptic drugs such as VPA. We summarized current clinical practice using TDM. We described the relationships between serum VPA concentration, clinical effect, and adverse drug reactions as well as the reference concentration range. It concluded that a therapeutic decision should not ultimately be based on serum VPA levels alone; other important factors should be considered including an interview with a patient and his medical history, clinical laboratory and pharmacogenetic data, and very importantly, the patient’s individual therapeutic concentration of VPA in serum.

There are two main processes that induce skin aging: extrinsic and intrinsic. Extrinsic aging is caused by environmental factors such as sun exposure, air pollution, smoking, and poor nutrition. Intrinsic aging reflects the genetic background especially in terms of cell viability and proliferation potential, and depends on time. It introduces unfavorable changes in the functioning of organs and in the external appearance of the body, especially visible on the skin. Wrinkles, discoloration and loss of facial contours can reduce the quality of everyday life and disrupt human social relationships. There are now a couple of theories of aging to explain this inevitable fact of being human like: genetic, Hayflick’s, mitochondrial, biochemical and protein impairments theories. Both surgical and non-surgical aesthetic procedures are used to maintain a beneficial appearance, rejuvenation and slow down skin aging. From year to year, public interest in the use of innovative anti-aging treatments increases, enabling the preservation of youthful appearance for a longer period than it results from the physiological life cycle. Non-surgical aesthetic treatments, delaying skin aging, activate natural mechanisms of cell renewal and accelerate their metabolism, stimulate the synthesis of fibroblasts to produce collagen, which is the main building element of the skin. The most effective treatments delaying skin aging currently include, among others lifting with polydioxane threads, skin regeneration with platelet rich plasma, microneedle and needle mesotherapy, plasmage lifting as well as dermabrasion and microdermabrasion treatments combined with chemical exfoliation. Professional and systematic stimulations of cells allow lengthening and restoring the beneficial appearance of the skin in all its layers. Treatments using polydioxane threads restore the distorted face oval and lift the skin around the eyes. The procedure using platelet-rich plasma activates cell growth factors, improving the regenerative processes of mature skin. A non-surgical face lift called plasmage, allows excess tissue to evaporate in order to reduce and eliminate wrinkles and drooping eyelids. Various types of mesotherapy and dermabrasion treatments affect the reconstruction of the skin structure, reduce fine wrinkles and stimulate fibroblasts to produce new collagen and elastic fibers.

Critically ill patients are at high risk of developing a life-threatening infection leading to severe shock and, as a consequence, multi-organ failure and even death. Optimal antimicrobial therapy, especially in the first 48 hours, is crucial to increasing patients' chances of survival. However, effective drug dosing is problematic because pathophysiological changes associated with the critical state of a disease affect their pharmacokinetic properties, mainly those drugs that are hydrophilic in nature. Concentrations of these drugs may be elevated in critically ill patients, mainly because of decreased renal clearance due to renal failure/damage. Conversely, antimicrobial concentrations may decrease due to increased volume of distribution and increased renal clearance, caused by the systemic inflammatory response syndrome, capillary leakage, reduced drug binding, intravenous fluids and inotropic drugs used. The frequency of simultaneous occurrence of numerous complications that may affect pharmacokinetic properties of drugs is excessively complicated by predicting their therapeutic concentrations. In general, situations where antimicrobial concentrations in serum of critically ill patients are too low dominate in clinical settings. And obtaining inappropriate plasma concentrations of patients is clinically important because it leads to ineffective eradication of pathogenic microorganisms and a lack of clinical improvement. In addition, too low drug levels trigger the development of multi-drug resistance, which is not only a medical but also a socio-economic problem. One of the major solutions to this problem seems to be the widespread use of plasma drug monitoring for individual adjustment of the dosage of antimicrobial drugs in a particular patient's clinical condition. However, despite the successful implementation of the beta-lactam antibiotic monitoring program in critically ill patients in Poland, several problems remain to be solved, such as insufficient documentation of the advantage of such a procedure and its clinical success, the lack of necessary technical preparation and specialist knowledge of medical staff in hospitals, which has an impact for the time of determining the concentration of antibacterial drugs in the patient plasma, even the possibility of monitoring drug concentration therapy does not solve the problem of obtaining the most optimal pharmacokinetic-pharmacodynamic indicators that determine the dosage selection. One solution, though not without its drawbacks, is to use population models to calculate the dosage of antimicrobial drugs. These models should take into account the state of mechanical ventilation, diagnostic category and glomerular filtration of the patient. However, also in such model preparation, there are problems such as the state of patients' kidney function, which may show large fluctuations and require frequent monitoring of creatinine, which is associated with additional work and time input, capillary leak affecting the value of distribution volume. The above pathophysiological changes significantly impede the development of appropriate models that would be adequate for use in optimization of the antimicrobial dosage in critically ill patients.

The purpose of this article is to present and analyse selected factors of income inequality associated with the labour market, socioeconomic conditions, tax systems, globalisation, freedom and financialisation in the post-socialist countries of Central and Eastern Europe and Central Asia from 1991 to 2019. Income inequality has significantly increased since the economic transition of the early 1990 s. The initial sharp increase in the Gini coefficient was partly expected due to institutional changes following the departure from the communist system, which kept inequality at a low level for ideologic reasons. However, the long-term development of income stratification depended on the approach taken by newly established institutions, external factors, and the preconditions of the transition. Research methods used in this study included cluster analysis employing Ward’s method, cross-sectional and panel regression, statistical analysis, and regression tree analysis with the CART algorithm. The results reveal the existence of several dominant trends in the development of income inequality and a link between the preconditions of economic transformation and the further evolution of the Gini coefficient. The study also identifies the most significant determinants and analyses their co-occurrence.