The article focuses on the specific design features of nonclinical studies (NCS) of in vivo gene therapy medicinal products which involve the administration of vectors with recombinant nucleic acids into the patient’s body for the correction of genetic disorders and treatment of oncological diseases. This work highlights the key aspects of conducting pharmacokinetic and toxicological studies, identified through the analysis of expert reports from global gene therapy medicinal products manufacturers. These aspects include dose selection and route of administration; identification of specific studies applicable to all in vivo gene therapy medicinal products and the justification of study lists for products using different types of vectors; as well as duration of studies and the selection of appropriate models to demonstrate product safety and to detect potential adverse effects associated with their use.

Objective : To demonstrate the advantages of using a modified aesthetic surgical approach in performing modified radical neck lymph node dissection and thyroidectomy in a patient diagnosed with papillary thyroid cancer. Case report : A clinical case of surgical treatment of a 47-year-old female patient who was admitted to the Scientific Research Institute – Ochapovsky Regional Clinical Hospital No. 1 with an confirmed diagnosis of papillary thyroid cancer, staged сT1N1bM0. The disease was detected during a medical examination of the population and confirmed by ultrasound and cytology results. An ultrasound examination revealed characteristic features of papillary thyroid cancer with the presence of metastases in the regional lymph nodes on the left and focal changes in both thyroid lobes (TI-RADS 3-5). Fine-needle aspiration biopsy of the thyroid nodules and cervical lymph nodes confirmed the diagnosis of papillary thyroid carcinoma with metastasis to the left cervical lymph node. Surgical intervention was performed to remove the primary tumor and regional metastases, including total thyroidectomy, central neck lymph node dissection, and a left-sided type III modified radical neck dissection through an incision along the midline cervical fold. The surgical approach provided optimal conditions for performing a radical procedure while enabling reconstruction of the soft tissue structure of the neck, minimizing cosmetic defects and preventing potential complications. Conclusion : Extensive surgical interventions in aesthetically significant areas performed through standard approaches may sometimes negatively affect long-term cosmetic and functional outcomes. The proposed surgical approach, integrating principles of oncology, plastic and reconstructive surgery, systematizes experience from these disciplines to develop the most effective therapeutic strategies for complex cases, in which improving quality of life is a primary objective.

The article presents a clinical case of a 65-year-old female patient with stage IV adenocarcinoma of the right lung harboring an EGFR-mutated (L858R). The key feature of this case is the sequential modification of targeted therapy: initial stabilization with osimertinib, transient progression with associate complications during Gefitinib therapy, and subsequent restoration of disease control following reintroduction of osimertinib. A comprehensive palliative care approach is described in detail, including repeated thoracenteses, long-term pleural drainage, and supportive therapy aimed at symptom control and maintenance of the patient’s functional status. This case highlights the importance of integrating palliative interventions into oncological practice from the early stages of treatment, as well as the advantages of original targeted agents in overcoming tumor resistance.

Unruptured cerebral aneurysms are detected in 3–5% of the adult population. Aneurysm rupture results in intracranial hemorrhage, with a mortality rate of approximately 45% and disability in about 30% of cases. Risk assessment scales for rupture of unruptured aneurysms (UCAS, ISUIA, PHASES, UIATS, ELAPSS) were developed to guide treatment strategy; however, their practical application has revealed a systematically underestimation of hemorrhage risk. In particular, a meta-analysis of more than 1,500 cases of aneurysmal hemorrhage demonstrated that 50–80% of the observed aneurysms had initially been classified as low risk, indicating significant limitations of current rupture risk assessment tools and highlighting the need for the development of dynamic models to predict hemorrhage probability that account for changes in clinical status and aneurysm morphology over time. The presented clinical case of middle cerebral artery aneurysm management illustrates the necessity to transform current approaches to determining treatment strategies for unruptured aneurysms.

Background: Currently, the primary laboratory profile of trace element status in individuals consuming alcohol and other psychoactive substances, as well as the main mechanisms and consequences of these changes, is well understood. It substantiates the need for further research development for assessing the potential to monitoring the development and progression of dependence syndrome and evaluating the effectiveness of therapy and rehabilitation.Objective: To characterize the features of the trace element composition of hair in patients with alcohol and psychostimulant dependence syndrome during the first three months of the rehabilitation period.Materials and methods: The study involved three groups of subjects, including a group of 30 healthy volunteers. The second group (n=35) consisted of patients with alcohol dependence syndrome, the third group (n=31) included patients with psychostimulant dependence syndrome. Biological samples were collected at two stages of the study: upon admission of patients to a medical and preventive institution for rehabilitation and 3 months after its start. The trace element composition in subjects’ hair was determined by inductively coupled plasma optical emission spectrometry.Results: At baseline, patients with alcohol dependence syndrome were characterized by a 2.0-fold decrease in calcium levels and a 2.7-fold increase in manganese levels in their hair. Three months after the start of rehabilitation, calcium levels increased to within the control range. Iron concentration increased 4.1-fold relative to baseline. Manganese levels remained elevated with a 3.6-fold increase. In patients with psychostimulant dependence syndrome, manganese levels were elevated 2.7-fold at baseline and 4.7-fold after three months. Distribution of the second group into subgroups made it possible to establish that in the abstinent subgroup from alcohol consumption, the baseline iron levels were 3.4 times higher, and zinc levels were 23% higher compared to the subgroup of individuals who experienced ethanol relapse.Conclusions: Patients with psychoactive substance dependence syndrome were characterized by high manganese concentrations, otherwise, the laboratory profile was similar to control values. A detailed analysis revealed that the onset of alcohol relapse was associated with reduced levels of iron and zinc in hair.

Background: Primary tracheal cancer is an extremely rare form of cancer. Of particular concern is the situation when such a primary tumor occurs at the site of a previously performed reconstructive surgery due to cicatricial stenosis of the trachea. This combination of factors significantly complicates the diagnosis and treatment of the disease, turning each such clinical case into a unique case of skin malignancy, previously used to replace a defect in the anterior wall of the trachea, requiring special attention from specialists.Materials and Methods: The subject of the study was a patient with primary tracheal cancer who underwent reconstructive plastic surgery about 30 years ago, including the use of a cervical skin flap to repair the anterior wall of the trachea in post-tracheostomy cicatricial granulation stenosis. At the time of detection of tumor restenosis, the patient was undergoing treatment for infiltrative tuberculosis of the upper lobe of the right lung. After a course of anti-tuberculosis drug treatment, cervicosternotomy, circular tracheal resection with the formation of an anastomosis with a skin pad, and cervical-mediastinal lymphadenectomy were performed. During the intraoperative revision performed after a transverse tracheotomy, a cauliflower-like tumor was identified, originating from the distal part of the cutaneous tracheal graft, which was formed approximately 30 years ago during the final stage of surgery for cicatricial tracheal stenosis. Morphological examination of the tissue sample revealed keratinizing squamous cell carcinoma of mucosa from the skin previously used for tracheal reconstruction. No metastases were found in the lymph nodes. The postoperative period was uneventful, with uninterrupted continuation of anti-tuberculosis therapy.Results: The clinical case demonstrates the potential for malignant transformation of skin tissue previously used in reconstructive surgery for cicatricial stenosis of the trachea, as well as confirming the possibility of radical surgery with complete tumor removal (R0).Conclusions: Malignant transformation of cutaneous tissue incorporated into the respiratory tract during reconstructive surgery is a possible but extremely rare complication of staged reconstructive surgery. This clinical case represents a unique phenomenon, highlighting the importance of oncological monitoring and long-term follow-up of patients who have undergone such reconstructions.

Background: Type 1 diastematomyelia is a rare congenital spinal anomaly in which the spinal cord is separated by an osseous septum into 2 hemicords. Pediatric patients often present with neurological disorders and spinal deformities, which significantly impair their quality of life. Conventional surgical treatment includes septal resection and osteoplastic laminotomy but is often accompanied by significant traumatization, risks of damage to neural structures, increased intraoperative blood loss, iatrogenic spinal instability, and postlaminectomy spinal deformity progression. Modern 3D technologies enable to improve the accuracy of surgery, ensuring gentler treatment of the posterior spinal structures.Objective: To compare the effectiveness and safety of an individualized navigation template for osteoplastic laminotomy with those of the traditional surgical approach in patients with type 1 diastematomyelia.Materials and methods: The retrospective study included 13 patients (age, 4-12 years) with type 1 diastematomyelia. In the main group (n=6), we used individualized 3D navigation templates, whereas the control group (n=7) underwent conventional laminotomy. The data (operation time, blood loss volume, C-reactive protein level, complications) were analyzed using Statistica (TIBCO Software Inc, USA). Quantitative values were compared using a t test, and P < .05 was considered statistically significant.Results: The application of the navigation template significantly reduced osteotomy duration and blood loss compared with the conventional method (P < .05). The C-reactive protein level on the first postoperative day did not differ significantly between the groups (P > .05), indicating a similar postoperative inflammatory response. One control patient had a neurological complication, which resolved within 3 months.Conclusions: An individualized navigation template for type 1 diastematomyelia increases the accuracy of bone resection and reduces the traumatic nature of the surgery. This approach holds promise for its widespread implementation in clinical practice, particularly in cases of complex congenital spinal anomalies.