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THE PERSONALISED ASPECTS OF DEVELOPMENT OF INFLAMMATORY COMPLICATIONS IN FRACTURES OF BONES OF EXTREMITIES

Miromanov A.M., Trubitsin M.V., Mironova O.B., Miromanova N.A.

Chita State Medical Academy, Chita, Russia

Currently, pyoinflammatory complications after fractures of the extremities still present the complex and unresolved problem [1-4]. Multiple factors [4, 5, 6], including hereditary (genetic) ones [7, 8], play the significant role in development, course and outcome of the inflammatory process during traumatic disease. Development of complications after fractures leads to worsening moral and physical condition of a patient, as well as to significant economic costs for treatment. Therefore, searching the techniques of personalized prediction is a priority direction of the modern medicine [9].
Unfortunately, the domestic traumatology and orthopedics do not demonstrate sufficient findings of the genetic aspects of diseases and complications. It requires more proper examination, particularly, in bone injuries and pyoinflammatory complications. Investigations of the genes, which play the significant role for development of such complications in traumatic disease, are the perspective task, and its solution can give the new data about pathogenesis with appearance of possibilities for prediction of development and carrying out the necessary personalized preventive measures.
The objective of the study – to construct a mathematical forecasting model and to reveal the personified criteria of development of inflammatory complications in patients with fractures of the bones of the extremities on the basis of the revealed clinical, laboratory and tool indicators.

MATERIALS AND METHODS

The prospective (cohort, longitudinal) study included 163 patients at the age of 20–40with fractures of the extremities. The patients received the treatment in the Chita City Clinical Hospital No.1. The patients were distributed into the groups. The group 1 (n = 83) included the patients with uncomplicated course of the fractures of the long bones of the extremities (the wounds with primary tension, removal of sutures on the days 9–10 after surgery, absence ofcomplications within 1 year). The patients with the pyoinflammatory complications were included into the group 2 (n = 80). This group combined 2 subgroups: the subgroup 1 – the patients with purulence in the postsurgical wounds in the early period (the days 3–5, n = 31), the subgroup 2 (n = 49) –the patients with chronic traumatic osteomyelitis (wound healing with primary tension, but chronic traumatic osteomyelitis was diagnosed in the late postsurgical period, in 3 months after the surgery). The control group (n = 100) included the almost healthy patients at the age of 20–40.
The study corresponded to the ethical principles of World Medical Association Declaration of Helsinki (1964, 2011) and the Rules for Clinical Practice in the Russian Federation confirmed by the Order of Health Ministry of Russia, June 19, 2003, No.266.
The groups of the patients were created in concordance with the classification of fractures by Muller M.E. et al [10] (the table 1).

Table 1. Distribution of patients according to location and features of fractures (abs., %)

After comparison of the clinical, laboratory and instrumental parameters in the examined group we have not identified any statistically significant differences between the parameters in opened and closed fractures; as result, the groups were combined only according to the type of a complication.
Early inflammatory complications (the days 3-5 after surgery) were characterized by purulence in the line of a fracture complicated by periostitis, phlegmona and abscesses in the periosteal soft tissues. The diagnosis of chronic traumatic osteomyelitis was verified on the basis of the clinical data (local painfulness, hyperemia, swelling around the injury site, increasing body temperature, purulent discharge, fistula, trophic disorders in view of dark brown pigmentation of the skin and the scars etc.) and the X-ray picture (soft tissue edema, periosteal thickening or elevation and local osteoporosis, lamellated periosteal reaction, formation of cavities with sequesters and others) [11].
The patients with closed and opened fractures of the bones received the surgical treatment during the first two hours after hospital admission. Opened reposition and metal fixation (functional) were conducted for closed injuries. As for the patients with opened fractures, after primary surgical preparation of an opened fracture they received the fixation with the external fixing devices and draining. The conservative treatment was realized according to the actual guidelines [11, 12].
The results of the clinical, laboratory and instrumental examination (210 values) were estimated in the multivariable predictive regression model. The parameters were examined at the moment of hospital admission and on the days 2, 5, 10 and 90 after traumatic disease. The reviewed anamnestic and clinical data corresponded to the recommendations for diagnosis of fractures and complications [11, 12]. The laboratory results (the peripheral venous blood was the material for the examination): the value of lymphocytic and thrombocytic adhesion (LTA) and lymphocytic thrombocytic index (LTI); cytokines (IL1α, IL1β, TNFα, IL-4, IL-10, TGFα, TGF1β), the parameters of adenylic (ATP, ADP, AMP) and antiproteinase system (α₂-macroglobulin, α₁- antitrypsin); the values of the system POL-antioxidants (conjugated diene structures, ketodiens and conjugated trienes, TBA-active products, malondialdehyde, general antioxidant activity). The examination of the above-mentioned data was conducted with use of the standard techniques [13]. The point mutations were selected for the genetic tests: TNFα in the position 308 (G>A), IL-4 in the position 589 (C>T), IL-10 in the position 592, 819 (C>T) and 1082 (G>A). The amplification of the fragment of the examined genes was conducted in the thermal cycle (the model Re Bis – M111, Bis-N Ltd., Novosibirsk). The study was performed with using the standard sets of the primers from the scientific and industrial company Litekh-SNP (Moscow). Visualization of the amplified products was conducted with electrophoresis in 3 % agarose gel with ethidium bromide in transmitted ultraviolet light [14]. The instrumental techniques: laser doppler flowmetry (the values of microcirculatory bed); X-ray examination [12, 13].                      

RESULTS AND DISCUSSION

The multivariate (stepwise with inclusion) regression analysis identified the high relationship between -589Т/T gene IL4 and development of the inflammatory complications in the patients in the early and late periods of injury. The accuracy of the analysis increased significantly after addition of the genotype -308А/А of the gene TNFα, whereas other values did not make any significant influence on the prognosis (the table 2).

Table 2. Predictive significance of parameters in development of early and late inflammatory complications in fractures of extremities

Note: n – number of observed cases; β – regression coefficient; Std. Err. of β – standard error β; В – free term (length); Std. Err. В – standard error В; p – level of statistical significance (reliable for при р < 0.05).

The coefficient (K) of correlation (multiple) was not registered on the level 0.983, determination K (R²) was 0.966, and the level of significance of the regression model was < 0.0000001. The genotype -589Т/T of the gene IL-4 was the most important predictive factor of the early (purulence) and late (osteomyelitis) inflammatory complications in fractures (56-fold increasing risk). The genotype -308А/А of the gene TNFα makes the significant influence on the diagnosis of the inflammatory process (44-fold increasing risk) (the table 2).
The received predictive model demonstrates the sufficiently high sensitivity and reliability (p < 0.0000001). This fact is confirmed by the high degree of correspondence to the empirical data (R²), the lineal dependence of the factors of influence and response, i.e. development of a complication (K), but also the considered parameters influencing on the complications (only two parameters were identified: corrected R² did not differ from the basic one) [15].
The importance of the molecular and genetic tests for diagnostics of various complications is doubtless for the modern medicine. So, our previous studies showed that A/A genotype of the gene TNFα (G-308А) could be used as the unfavorable predictive criterion in development of pyoinflammatory complications in the late postsurgical period, as well as for estimation of severity of their course, because the mutation carriers with the homozygote type showed more severe and long term course of the wound infection [14]. The similar findings were received after the examination of IL-4 (C 589T) polymorphism [16]. However the consideration of predictive significance of the criteria in the groups with both early and late inflammatory complications (traumatic osteomyelitis) in fractures and their inclusion into the multiple regression model identified two most significant values: the genotype -589Т/T of the gene IL-4 and the genotype -308А/А of the gene TNFα. It can indicate the high predictive significance of combination of carriage of these mutant genotypes.
The study of molecular and genetic aspects of the complications in pathology of the locomotor system is a perspective direction and it can promote future realization of the long term individual prognosis. Development and creation of “the genetic passport” will allow performing the measures for preventing development of a possible complication and decrease the risk of its course.

CONCLUSION

Identification of the genotype -589Т/Т of the gene IL-4 and the genotype -308A/A of the gene TNFα is the informative value of development of inflammatory complications in early and late periods of traumatic disease (including chronic traumatic osteomyelitis).

REFERENCES:

1. Kanakaris N, Gudipati S, Tosounidis T, Harwood P, Britten S, Giannoudis PV. The treatment of intramedullary osteomyelitis of the femur and tibia using the Reamer-Irrigator-Aspirator system and antibiotic cement rods. Bone Joint J. 2014; 96-B(6): 783-788
2. Conterno LO, Turchi MD. Antibiotics for treating chronic osteomyelitis in adults. Cochrane Database Syst. Rev. 2013; Sep 6; (9): CD004439. An access regimen: https://www.ncbi.nlm.nih.gov/pubmed/24014191 (reference date: 02.01.2017)
3. Giannoudis PV, Harwood PJ, Kontakis G., Allami M, Macdonald D, Kay SP et al. Long-term quality of life in trauma patients following the full spectrum of tibial injury (fasciotomy, closed fracture, grade IIIB/IIIC open fracture and amputation). Injury. 2009; (40): 213-219
4. Onoprienko GA, Buachidze OSh, Eremin AV, Savitskaya KI, Zubikov VS, Voloshin VP. Surgical treatment of patients with chronic purulent damage of bones and large joints of extremities. Surgery. 2005; (8): 29-35. Russian (Оноприенко Г.А., Буачидзе О.Ш., Еремин А.В., Савицкая К.И., Зубиков В.С., Волошин В.П. Хирургическое лечение больных с хроническим гнойным поражением костей и крупных суставов конечностей //Хирургия. 2005. № 8. С. 29-35)
5. Huang CC, Tsai KT, Weng SF, Lin HJ, Huang HS, Wang JJ et al. Chronic osteomyelitis increases long-term mortality risk in the elderly: a nationwide population-based cohort study. BMC Geriatr. 2016; (31): 16-72
6. Bonnevialle P. Operative treatment of early infection after internal fixation of limb fractures (exclusive of severe open fractures). Orthop. Traumatol. Surg. Res. 2017; Jan 2. pii: S1877-0568(16)30186-4. An access regimen: https://www.ncbi.nlm.nih.gov/pubmed/28057476 (reference date: 02.01.2017)
7. Osman AE, Mubasher M, ElSheikh NE, AlHarthi H., AlAlallah IA, Elbeshir AA et al. Investigation of polymorphisms in anti-inflammatory cytokine genes in hematogenous osteomyelitis. Genet. Mol. Res. 2015; (14): 16981-16986
8. Valle-Garay E, Montes AH, Corte JR, Meana A, Fierer J, Asensi V. tPA Alu (I/D) polymorphism associates with bacterial osteomyelitis. J. Infect. Dis. 2013; (208): 218-23
9. Mironov SP. A condition of orthopedic and traumatological service in the Russian Federation and the prospects of introduction of innovative technologies in traumatology and orthopedics. Herald of Traumatology and Orthopedics named after N.N. Рriorov. 2010; (4): 10-13. Russian (Миронов С.П. Состояние ортопедо-травматологической службы в Российской Федерации и перспективы внедрения инновационных технологий в травматологии и ортопедии // Вестник травматологии и ортопедии им. Н.Н. Приорова. 2010. № 4. С. 10-13)
10. Muller ME, Nazarian S, Koch P. The Comprehensive Classification of Fractures of Long Bones. Springer-Verlag Heidelberg-New York, 1996. 32 р.
11. Clinical surgery: national management: in 3 vol. Under the editorship of Savelyev VS, Kirienko AI. M.: GEOTAR-Media, 2008; Vol. 1: 864 p. Russian (Клиническая хирургия: национальное руководство: в 3 т. /под ред. В.С. Савельева, А.И. Кириенко. М.: ГЭОТАР-Медиа, 2008. Т. I. 864 с.)
12. Traumatology: the national manual. Uunder the editorship of Kotelnikov GP, Mironov SP. M.: GEOTAR-media, 2013. 944 p. Russian (Травматология: национальное руководство /под ред. Г.П. Котельникова, С.П. Миронова. М.: ГЭОТАР-Медиа, 2013. 944 с.)
13. Miromanov AM, Namokonov EV. Prognostic criteria of development of complications in fractures of bones of extremities. Chita: CSMA Publ., 2014; 175 p. Russian (Мироманов А.М., Намоконов Е.В. Прогностические критерии развития осложнений при переломах костей конечностей. Чита: РИЦ ЧГМА, 2014. 175 с.)
14. Miromanov AM, Mironova OB, Trubitsyn MV, Vitkovsky YuA. Polimorfizm of the gene of TNF-α (G-308A) in patients with pyoinflammatory complications with fractures of long bones of extremities in Zabaykalsky Kray. Zabaikalsky Medical Herald. 2013; (1): 41-45. An access regimen: http://chitgma.ru/zmv2 (Access date: May 20, 2013). Russian (Мироманов А.М., Миронова О.Б., Трубицын М.В., Витковский Ю.А. Полиморфизм гена TNF-α (G-308А) у больных с гнойно-воспалительными осложнениями при переломах длинных костей конечностей в Забайкальском крае //Забайкальский медицинский вестник. 2013. № 1. С. 41-45. Режим доступа: http://chitgma.ru/zmv2. Дата доступа: 20.05.2013)
15. Mikhalevich IM. Regression analysis (use in medical researches with application of Statistica): the manual for doctors. Irkutsk: ISMA Publ., 2012. 32 p. Russian (Михалевич И.М. Регрессионный анализ (использование в медицинских исследованиях с применением ППП Statistica) : пособие для врачей. Иркутск : РИО ГБОУ ДПО ИГМАПО, 2012. 32 с.)
16. Miromanov AM, Mironova OB, Uskov SA, Trubitsyn MV, Gusev KA. Polimorfizm of the gene of IL-4 in patients with the complicated course of fractures of long bones of extremities. Postgraduate Medical Student. 2013; (5.3): 434-440. Russian (Мироманов А.М., Миронова О.Б., Усков С.А., Трубицын М.В., Гусев К.А. Полиморфизм гена интерлейкина-4 у больных с осложненным течением переломов длинных костей конечностей //Врач-аспирант. 2013. № 5.3 (60). С. 434-440)

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