An advanced method of bone tissue reconstruction in patients with osteoregeneration disorders (experience with clinical application of scaffold technologies) [ПЕРСПЕКТИВНЫЙ МЕТОД ВОССТАНОВЛЕНИЯ КОСТНОЙ ТКАНИ У ПОСТРАДАВШИХ С ТЯЖЕЛЫМИ НАРУШЕНИЯМИ ОСТЕОРЕГЕНЕРАЦИИ (ОПЫТ КЛИНИЧЕСКОГО ПРИМЕНЕНИЯ СКАФФОЛД-ТЕХНОЛОГИЙ)]

Nonunion and defects of bone tissue are the same complex of comparable pathological processes − impairment of reparative osteoregeneration of the diaphysis of the long bone. With objective of recovery of bone tissue and improvement in extremity function, the original technique for replacement of a bone defect in combination with internal fixation was offered. Materials and methods. We studied 119 patients with non-unions and 19 wounded persons with a bone defect in the diaphysis of the long bone. In the main group of patients, the bone defect was plastered with autobone and collagen hydrogel. Internal osteosynthesis was performed. In the control group, the bone tissue defect was restored by the method of G.A. Ilizarov. The result of treatment was assessed clinically, radiographically and by testing. Results. In the main group of patients with non-unions (61 people), the post-resection bone defect was restored in the mid-physiological terms of the segment bone fusion (mean time – 107.41 ± 41.29 days), which was 1.5 times better than the similar result of the control group (58 patients) – on average 170.45 ± 7.30 days. In the main group of wounded with post-traumatic bone defect (9 people), restoration of the integrity of the bone tissue was completed on average after 267.57 ± 32.61 days, which was 1.4 times faster than in the control group (10 people). According to the test results in the main group, a good effect of treatment was obtained by 8-24 % more, than in the control group. Conclusion. Collagen hydrogel is an effective matrix for the construction of a tissue-engineered structure when replacing a bone defect. The proposed algorithm for the treatment of patients with severe disorders of reparative osteoregeneration allows restoring the integrity of the bone and obtaining excellent and good treatment results. © 2021 The Charity Fund of Clinical Center of Miners' Health Protection. All rights reserved

Aesthetic surgery of the lower limbs in current orthopedic practice

Introduction Correction of the shape of the lower extremities for aesthetic puposes has specific features that are associated with the role of the patient in the treatment process and assessment of results. An important element is the relationship between the appearance of the limb and changes in the axes of the skeleton. Aim of study Assessment of many-years of experience in orthopedic correction of the shape of the lower extremities for aesthetic purposes, discussion of possibilities, analysis of problems and search for possible ways to prevent them. Methods The material of the study was 123 patients who underwent aesthetic surgical correction in the period from 2005 to 2020. Their long-term results were followed in the period from 6 months to 11 years. In all cases, operations were performed simultaneously on both limbs. The total number of operations, thus, amounted to 246. The main indication for surgery was the so-called true O-shaped curvature (varus deformity) of the lower extremities. In all cases, the main elements of the operation were osteosynthesis with the Ilizarov apparatus and osteotomy of the tibia. Wires and half-pins were used as transosseous elements. To assess the main reference lines and angles (RLA), X-ray examination of the lower extremities was performed with the capture of the hip and ankle joints. Results and discussion Corrective manipulations in the group of patients led to a change in the position of the main RLA. Before treatment, MAD value was 15 ± 7 mm, after correction MAD = -2 ± 4 mm, before surgery MPTA = 85 ± 40, after correction MPTA = 91 ± 20. Subjective satisfaction was reported in 114 (92.7 %) cases. Subjectively unsatisfactory results were recorded in 4 (3.3 %) cases; objectively unsatisfactory results were detected in 5 (4.1 %) cases. Conclusions Aesthetic surgery of the lower extremities is a part of orthopedic practice and has its specific features due to the goal of realizing the patient's wishes about changing the appearance of the lower extremities indirectly by performing operations on the skeleton. Corrective surgery should be considered as a preventive intervention aimed at preventing the development of gonarthrosis in old age. The key to a good result is a careful selection of candidates for surgery and their compliance, along with a thorough explanation of the principles and features of correction. © 2021. Artemev A.A., Brizhan L.K., Davydov D.V., Bytdaev Z.M., Kashoob Á.M., Shipulin A.A., Gululyan G.G. All rights reserved

Evidence of CYP3A Allosterism In Vivo: Analysis of Interaction Between Fluconazole and Midazolam

The allosteric effect of fluconazole (effector) on the formation of 1’-hydroxymidazolam (1’-OH-MDZ) and 4-hydroxymidazolam (4-OH-MDZ) from the CYP3A4/5 substrate, midazolam (MDZ), was examined in healthy volunteers. Following pre-treatment of fluconazole, AUC(4-OH)/AUC(MDZ) increased 35–62%, while AUC(1’-OH)/AUC(MDZ) decreased 5–37%; AUC(1’-OH)/AUC(4-OH) ratio decreased 46–58% by fluconazole and had no association with CYP3A5 genotype. 1’-OH-MDZ formation in vitro was more susceptible than 4-OH-MDZ formation to inhibition by fluconazole. Fluconazole decreased the intrinsic formation clearance ratio of 1’-OH-MDZ/4-OH-MDZ to an extent that was quantitatively comparable to in vivo observations. The elimination clearance of midazolam metabolites appeared unaffected by fluconazole. This study demonstrated that fluconazole alters midazolam product formation both in vivo and in vitro in a manner consistent with an allosteric interaction. The 1'-OH-MDZ/4-OH-MDZ ratio may serve as a biomarker of such interactions between midazolam, CYP3A4/5 and other putative effectors