Exome Sequencing for the Diagnostics of Osteogenesis Imperfecta in Six Russian Patients.

Osteogenesis imperfecta (OI) is a group of inherited disorders of connective tissue that cause significant deformities and fragility in bones. Most cases of OI are associated with pathogenic variants in collagen type I genes and are characterized by pronounced polymorphisms in clinical manifestations and the absence of clear phenotype-genotype correlation. The objective of this study was to conduct a comprehensive molecular-genetic and clinical analysis to verify the diagnosis of OI in six Russian patients with genetic variants in the COL1A1 and COL1A2 genes. Clinical and laboratory data were obtained from six OI patients who were observed at the Medical Genetics Center in Saint Petersburg from 2016 to 2023. Next-generation sequencing on MGISEQ G400 (MGI, China) was used for DNA analysis. The GATK bioinformatic software (version 4.5.0.0) was used for variant calling and hard filtering. Genetic variants were verified by the direct automatic sequencing of PCR products using the ABI 3500X sequencer. We identified six genetic variants, as follows pathogenic c.3505G>A (p. Gly1169Ser), c.769G>A (p.Gly257Arg), VUS c.4123G>A (p.Ala1375Thr), and c.4114A>T (p.Asn1372Tyr) in COL1A1; and likely pathogenic c.2035G>A (p.Gly679Ser) and c.739-2A>T in COL1A2. In addition, clinical cases are presented due to the presence of the c.4114A>T variant in the COL1A2 gene. Molecular genetics is essential for determining different OI types due to the high similarity across various types of the disease and the failure of unambiguous diagnosis based on clinical manifestations alone. Considering the variable approaches to OI classification, an integrated strategy is required for optimal patient management.

Definitive internal fracture fixation followed by staged free flap coverage ("fix followed by flap" protocol) for open Gustilo type IIIB fractures.

BACKGROUND: Although the concept of the "fix and flap" approach, in which definitive fracture fixation and flap coverage are completed in a single procedure at the earliest opportunity may seem ideal for the treatment of Gustilo type IIIB open fractures, the individual circumstances of patients, such as polytrauma or multiple fracture cases may not allow for the immediate fracture fixation and flap coverage ("fix and flap" approach). In our hospital, patients with Gustilo type IIIB open fractures are treated with definitive internal fixation of the fracture followed by staged flap coverage ("fix followed by flap" protocol) when the "fix and flap" approach was not feasible due to the patient's condition or difficulty in coordinating surgery schedules. The "fix followed by flap" protocol provides benefits in terms of flexibility in adjusting the surgical timetable, simplifying the planning of flap coverage following fracture fixation, and minimizing individual surgical invasion. METHODS: We reviewed 10 cases of severe open fractures treated with the "fix followed by flap" protocol and evaluated their outcomes. All surgical procedures, including wound debridement, fracture fixation, and flap coverage, were performed by orthoplastic surgeons specializing in both fracture surgery and microsurgery including soft tissue reconstruction. RESULTS: All free flaps survived, and no partial necrosis was observed. None of the patients developed postoperative deep infection up to the last follow-up. Fracture union was achieved in all patients with or without autologous bone grafts. The median time for union was 9.4 months (range, 4-12 months). CONCLUSIONS: This study presents favorable outcomes of treatment for Gustilo type IIIB open fractures with fracture fixation followed by staged flap coverage ("fix followed by flap" protocol). Despite a delay in flap coverage, the consistency of treatment provided by orthoplastic surgeons may have contributed to the favorable outcomes in this study.

Are there specific clinical risk factors for the occurrence of multiple fractures? The FRISBEE study.

This study showed additional clinical risk factors for the occurrence of multiple fractures with regards to a single fracture, with often higher hazard ratios. It would be important to include the risk of the occurrence of multiple fractures in future prediction models. PURPOSE: To identify clinical risk factors (CRFs) which would specifically increase the risk of multiple fractures. METHODS: Data of the 3560 postmenopausal women of the FRISBEE study were analysed. The CRFs and the fractures are collected annually. The cohort was divided into three groups: those who had no incident fracture, those who had a single incident fracture and those who had 2 two or more incident fractures (i.e. multiple fractures). Statistical analyses were performed using Cox proportional hazards models. RESULTS: Among the 3560 subjects (followed for 9.1 (7.2-10.6) years), 261 subjects had two or more validated fractures during follow-up (146 were major osteoporotic fractures (MOFs)), 628 had one fracture (435 MOFs), 2671 had no fracture (2979 had no MOF); 157 subjects had two or more central fractures, 389 had only one and 3014 had none. The risk factors for those with multiple fractures at any site were age, history of fracture, history of fall, total hip bone mineral density (BMD), spine BMD and rheumatoid arthritis. For those with multiple MOFs, significant CRFs were age, history of fracture, parental hip fracture, total hip BMD and rheumatoid arthritis. CONCLUSION: We found in a prospective cohort study that there were more CRFs and higher hazard ratios for the occurrence of multiple fractures than for a single fracture.

[Current developments in primary and secondary surgical treatment of midface and periorbital trauma]. / Aktuelle Entwicklungen in der chirurgischen Primär- und Sekundärversorgung von Mittelgesichts- und periorbitalen Traumata.

Fractures of the periorbita and the midface are among the most common bony facial injuries. Aesthetic and functional reconstruction is a challenge in clinical routine. This article illustrates recent developments in the primary and secondary surgical treatment of midface and periorbital trauma. Resorbable patches and films increase the anatomic reconstructive capacity and enable treatment of extensive orbital fractures. Orbital fractures with involvement of supporting key structures are advantageously reconstructed using patient-specific implants (PSI), which are fabricated by computer-assisted manufacturing techniques and positioned by intraoperative navigation. If late complications such as bulbar malposition and enophthalmos have occurred after the initial procedure, they can be addressed by overcorrective restoration of orbital volume. The use of PSI for initial fracture restoration of the midface is not yet established but may be useful in re-osteotomies of misconsolidated fragments. Extensive midface defects with significant soft tissue involvement can be reconstructed using microvascular grafts. Consecutive reconstructive procedures may include orthognathic surgery and local flap reconstruction. In summary, the integration and advancement of computer-assisted techniques now offers individualized reconstruction procedures, which may be a viable alternative to conventional implants and compression miniplates. Future developments may focus on the search for innovative biomaterials, which can be integrated into computer-aided design and manufacturing processes.

Multidisciplinary cooperative first aid model for the treatment of patients with pelvic and multiple fractures.

Objectives: To retrospectively evaluate a multidisciplinary cooperative first aid model for the treatment of patients with pelvic and multiple fractures in the emergency department. Methods: The records of patients with pelvic fractures complicated with multiple fractures treated in our hospital from February 2020 to April 2021 were selected, of which 34 patients received conventional trauma first aid mode control group) and 34 patients received multidisciplinary joint first aid mode (study group). We compared pelvic function (Majeed functional score) and fracture reduction outcomes, as well as serum inflammatory factor levels and complication rates after treatment between the two groups. Results: The Majeed score in the study group (90. 15 ± 6.83) was higher than that in the control group (75. 47 ± 5.35), and the differences were statistically significant(P<0.05). The value for combined excellent and good rates of fracture reduction in the study group (85.29%, 29/34) was significantly higher than that in the control group (58.82%, 20/34), and the difference was statistically significant(P<0.05). We found similar levels of TNF-a and IL-6 between the two groups at admission(P>0.05); however, the serum levels of TNF-a and IL-6 in the study group were lower than those in the control group on the fifth day after admission, and the difference was statistically significant (P<0.05 or P<0.01). The incidence of complications in the study group (17.64%, 6/34) was significantly lower than that in the control group (61.76%, 21/34), the difference was statistically significant(P<0.05). Conclusion: The multidisciplinary cooperative first aid model for the treatment of patients with pelvic and multiple fractures can effectively shorten the treatment time, increase the excellent functional rehabilitation rate, inhibit the release of inflammatory factors, and reduce the incidence of complications (such as infections), when compared to the conventional trauma emergency system.

Multiple simultaneous fractures are associated with higher all-cause mortality: results from a province-wide fracture liaison service.

Mortality rates in our fracture liaison service ranged from 2.7% at year 1 to 14.8% at year 5 post-screening. Presentation with multiple simultaneous fractures at screening was associated with higher risk of death. This finding indicates the need for increased focus on this high-risk group. PURPOSE: To examine all-cause mortality rates in a provincial fracture liaison service (FLS) and the association between the index fracture type, particularly multiple simultaneous fractures, and the risk of death at follow-up. METHODS: This cohort study includes fragility fracture patients aged 50+, enrolled in a provincial FLS in Ontario, Canada, between 2007 and 2010. All-cause mortality was assessed using administrative data. Multivariable Cox proportional hazards model was used to examine the risk of death 5 years after screening. RESULTS: Crude mortality rates for 6543 fragility fracture patients were 2.7% at year 1, 5.6% at year 2, and 14.8% at year 5 after screening. After adjusting for age and sex, and relative to distal radius fracture, patients with multiple (simultaneous) fractures at screening had a higher risk of dying (HR = 1.8, 95%CI 1.3-2.4), followed by those with a hip fracture (HR = 1.5, 95%CI 1.3-1.8), a proximal humerus fracture (HR = 1.4, 95%CI 1.2-1.7), and other single fractures (HR = 1.4, 95%CI 1.1-1.7). Having an index ankle fracture was not associated with the risk of death over a distal radius fracture. As compared to the 50-65 age group, patients 66 years and older had a higher risk of death (for 66-70 age group: HR = 2.5, 95%CI 1.9-3.3; for 71-80: HR = 4.3, 95%CI 3.5-5.4; and for 81+: HR = 10.6, 95%CI 8.7-13.0). Females had a lower risk of death (HR = 0.5, 95%CI 0.5-0.6) than males. CONCLUSIONS: Presenting with multiple fractures was an indicator of higher risk of death relative to a distal radius fracture. This finding indicates the need for increased focus on this high-risk group.

Traumatic multiple cervical spine injuries in a patient with osteopetrosis and its management.

STUDY DESIGN: Single case report. OBJECTIVE/PURPOSE: To report multiple level fractures of cervical spine in a patient with osteopetrosis and its management. Osteopetrosis is a rare inherited condition characterized by defective remodeling resulting in hard and brittle bones with diffuse osteosclerosis. Fractures of spine are rare as compared to the common long bone fractures. We report a case of traumatic multiple level fractures of cervical spine in osteopetrosis and its management which has rarely been reported in the literature before, if any. METHODS: 17-year-old boy presented with severe tenderness in neck and restricted range of motion following a trivial injury to the neck in swimming pool. The neurology was normal and he was diagnosed to have autosomal dominant osteopetrosis on evaluation. Imagining findings, clinical course and the method of treatment are discussed. RESULTS: Radiological evaluation revealed presence of multiple level fractures of cervical vertebrae with end plate sclerosis. Patient was managed with cervical skeletal traction in appropriate extension position for 6 weeks followed by hard cervical collar for another 6 weeks. Follow-up radiographs at 18 months and 2.5 years showed healed fractures with no residual instability or symptoms. CONCLUSION: The case report discusses rare occurrence of multiple level fractures of cervical spine following trivial injury to the neck in a patient with osteopetrosis and its treatment with conservative management.

Potential blindness in children of patients with hereditary bone disease.

Mono- and bi-allelic mutations in the low-density lipoprotein receptor related protein 5 (LRP5) may cause osteopetrosis, autosomal dominant and recessive exudative vitreoretinopathy, juvenile osteoporosis, or persistent hyperplastic primary vitreous (PHPV). We report on a child affected with PHPV and carrying compound mutations. The father carried the splice mutation and suffered from severe bone fragility since childhood. The mother carried the missense mutation without any clinical manifestations. The genetic diagnosis of their child allowed for appropriate treatment in the father and for the detection of osteopenia in the mother. Mono- and bi-allelic mutations in LRP5 may cause osteopetrosis, autosomal dominant and recessive exudative vitreoretinopathy, juvenile osteoporosis, or PHPV. PHPV is a component of persistent fetal vasculature of the eye, characterized by highly variable expressivity and resulting in a wide spectrum of anterior and/or posterior congenital developmental defects, which may lead to blindness. We evaluated a family diagnosed with PHPV in their only child. The child presented photophobia during the first 3 weeks of life, followed by leukocoria at 2 months of age. Molecular resequencing of NDP, FZD4, and LRP5 was performed in the child and segregation of the observed mutations in the parents. At presentation, fundus examination of the child showed a retrolental mass in the right eye. Ultrasonography revealed retinal detachment in both eyes. Thorough familial analysis revealed that the father suffered from many fractures since childhood without specific fragility bone diagnosis, treatment, or management. The mother was asymptomatic. Molecular analysis in the proband identified two mutations: a c.[2091+2T>C] splice mutation and c.[1682C>T] missense mutation. We report the case of a child affected with PHPV and carrying compound heterozygous LRP5 mutations. This genetic diagnosis allowed the clinical diagnosis of the bone problem to be made in the father, resulting in better management of the family. It also enabled preventive treatment to be prescribed for the mother and accurate genetic counseling to be provided.

A homozygous B3GAT3 mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes.

Linkeropathies are a group of syndromes characterized by short stature, radio-ulnar synostosis, decreased bone density, congenital contractures and dislocations, joint laxity, broad digits, brachycephaly, small mouth, prominent eyes, short or webbed neck, congenital heart defects and mild developmental delay. Linkeropathies are due to enzymatic defects in the synthesis of the common linker region that joins the core proteins to their glycosaminoglycan (GAG) side chains. The enzyme glucuronyltransferase 1, encoded by B3GAT3, adds the last four saccharides comprising the linker region. Mutations in B3GAT3 have been reported in two unrelated families with the same homozygous mutation (c.830G>A, p.Arg277Gln). We report on a patient with a novel homozygous B3GAT3 (c.667G>A, p.Gly223Ser) mutation and a history of multiple fractures, blue sclerae, and glaucoma. Our patient was a 12-month-old boy born to consanguineous parents and, like previously reported patients, he had bilateral radio-ulnar synostosis, severe osteopenia, an increased gap between first and second toes, bilateral club feet, and atrial and ventricular septal defects. He had the additional features of bilateral glaucoma, hypertelorism, upturned nose with anteverted nares, a small chest, a diaphragmatic hernia, multiple fractures, arachnodactyly, overlapping fingers with ulnar deviation, lymphedema, hypotonia, hearing loss, and perinatal cerebral infarction with bilateral supra- and infratentorial subdural hematomas. We highlight the extended phenotypic range of B3GAT3 mutations and a provide comparative overview of the phenotypic features of the linkeropathies associated with mutations in XYLT1, B4GALT7, B3GALT6, and B3GAT3.

Risk Factors of Deep Vein Thrombosis in Adults with Acute Compartment Syndrome Following Lower Extremity Fractures.

This study aimed to identify the risk factors of deep vein thrombosis (DVT) in adults with acute compartment syndrome (ACS) following lower extremity fractures. We collected data on adults with ACS following lower extremity fractures in our hospital from November 2013 to January 2021. Patients were divided into the DVT group and the non-DVT group according to whether they had DVT or not. The demographics, comorbidities, and admission laboratory examinations were computed by univariate analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis. In our study, the rate of DVT (26 of 110) was 23.6%. Univariate analysis showed that numerous factors were associated with the formation of DVT. Logistic regression analysis showed that patients with multiple fractures (P = .015, OR = 5.688), patients with a history of hypertension (P = .011, OR = 16.673), and patients with a higher BMI (P = .008, OR = 1.950) and FDP (P = .013, OR = 1.031) were relevant predictors of DVT. ROC curve analysis indicated 24.73 kg/m2 and 28.33 µg/mL were the cutoff values of BMI and FDP to predict the DVT, respectively. Furthermore, the combination of BMI and FDP had the highest diagnostic accuracy. Our findings identified multiple fractures, BMI, and FDP as independent risk factors for DVT in patients with ACS following lower extremity fractures and determined the cutoff values of BMI and FDP, helping us individualize the assessment of the risk of DVT to manage early targeted interventions.

Sequencing of panfacial fracture surgery: a literature review and personal preference.

BACKGROUND: Treating panfacial fractures (PFFs) can be extremely difficult even for experienced surgeons. Although several authors have attempted to systemize the surgical approach, performing surgery by applying a unidirectional sequence is much more difficult in practice. The purpose of this study was to review the literature on PFF surgery sequence and to understand how different surgical specialists-plastic reconstructive surgery (PRS) and oral maxillofacial surgery (OMS)-chose sequence and review PFFs fixation sequence in clinical cases. METHODS: The PubMed and Google Scholar databases were scoured for publications published up until May 2020. Data extracted from the studies using standard templates included fracture part, fixation sequence, originating specialist, and the countries. Bibliographic details like author and year of publication were also extracted. Also, we reviewed the data for PFFs patients in the Trauma Registry System of Dankook University Hospital from 2011 to 2021. RESULTS: In total, 240 articles were identified. This study comprised 22 studies after screening and full-text analysis. Sixteen studies (12 OMS specialists and 4 PRS specialists) used a "bottom-top" approach, whereas three studies (1 OMS specialist and 2 PRS specialists) used a "top-bottom" method. However, three studies (only OMS specialists) reported on both sequences. In our hospital, there were a total of 124 patients with PFF who were treated during 2011 to 2021; 64 (51.6%) were in upper-middle parts, 52 (41.9%) were in mid-lower parts, and eight (6.5%) were in three parts. CONCLUSION: Bottom-top sequencing was mainly used in OMS specialists, and top-bottom sequencing was used at a similar rate by two specialists in literature review. In our experience, however, it was hard to consistently implement unidirectional sequence suggested by a literature review. We realigned the reliable and stable buttresses first with tailoring individually for each patient, rather than proceeding in the unidirectional sequence like bottom-top or top-bottom.

Preliminary study of the characteristics of rib fractures and their impact on pulmonary ventilatory function.

BACKGROUND: This study aimed to investigate the pulmonary ventilation function (PVF) according to different types of rib fractures and pain levels. METHODS: This was a retrospective study of patients with thoracic trauma admitted to our ward from May 1, 2015, to February 1, 2017. Vital capacity (VC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF) were measured on admission. A numerical rating scale (NRS) was used for pain assessment. RESULTS: A total of 118 (85 males and 33 females) were included. The location of rib fractures did not affect the PVF. When the number of rib fractures was ≥5, the PVF was lower than in those with ≤4 fractures (VC: 0.40 vs. 0.47, P = 0.009; FEV1: 0.37 vs. 0.44, P = 0.012; PEF: 0.17 vs. 0.20, P = 0.031). There were no difference in PVF values between rib fractures with multiple locations and those with non-multiple locations (VC: 0.41 vs. 0.43, P = 0.202; FEV1: 0.37 vs. 0.39, P = 0.692; PEF: 0.18 vs. 0.18, P = 0.684). When there were ≥ 5 breakpoints, the PVF parameters were lower than those with ≤4 breakpoints (VC: 0.40 vs. 0.50, P = 0.030; FEV1: 0.37 vs. 0.45, P = 0.022; PEF: 0.18 vs. 0.20, P = 0.013). When the NRS ≥ 7, the PVF values were lower than for those with NRS ≤ 6 (VC: 0.41 vs. 0.50, P = 0.003; FEV1: 0.37 vs. 0.47, P = 0.040; PEF: 0.18 vs. 0.20, P = 0.027). CONCLUSIONS: When the total number of fractured ribs is ≥5, there are ≥5 breakpoints, or NRS is ≥7, the VC, FEV1, and PEF are more affected. TRIAL REGISTRATION: The trial was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, and individual consent for this retrospectively registered analysis was waived.

Antegrade nailing in femoral shaft fracture patients - comparison of outcomes of isolated fractures, multiple fractures and severely injured patients.

INTRODUCTION: Femoral shaft fractures in adults are high-energy fractures typically accompanied by additional fractures of the upper and lower extremities and brain, thoracic, or abdominal injuries. Intramedullary nailing enables early ambulation with a few complications, but rates of non-union remain high. Therefore, we aimed to compare bone union after femoral shaft fractures in adults (20-65 years old) depending on the injury severity and presence of multiple fractures. PATIENTS AND METHODS: This study retrospectively examined 178 patients (145 male and 33 female) who underwent intramedullary nailing for a femoral shaft fracture (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association 32 type) between January 2014 and December 2018 and were followed up for at least 1 year. Patients who underwent intramedullary nailing after the preliminary application of an external fixator were excluded. Patients were divided into groups with isolated femoral shaft fractures (IS group), an injury severity score of ≤14, and multiple fractures of the extremities and the pelvic bone (at least three locations), including a femoral shaft fracture (MU group), and severely injured (injury severity score ≥15) with femoral shaft fractures (SE group). Non-union rate by group and risk factors related to bone union and bone union rate according to time to full weight bearing were analyzed. RESULTS: In total, 29, 54, and 95 patients were assigned to the IS group, MU group, and SE group, respectively. Non-union was observed in two patients in the IS group (6.9%), six patients in the MU group (11.1%), and 11 patients in the SE group (11.6%). There were no significant differences in the bone union rate, according to multiple fractures (p=0.515) and injury severity score (p=0.561). Additionally, no differences in the bone union rate were observed according to the time to full weight bearing. Depending on open fracture (p=0.004) and fracture severity (p=0.011), the non-union rate showed a difference of up to four times or greater. CONCLUSIONS: When intramedullary nailing is performed to treat femoral shaft fractures, multiple fractures and severe trauma do not directly affect bone union. However, it should be noted that open fracture and greater fracture severity lead to higher chances of non-union.

Effect of Single Versus Multiple Fractures on Systemic Bone Loss in Mice.

Systemic bone loss after initial fracture contributes to an increased risk of secondary fracture. Clinical research has revealed an association between the risk of future fracture and the number or magnitude of prior fractures. However, the change in systemic bone mass after single versus multiple fractures is unknown. We used ipsilateral femur and tibia fractures as multiple fractures and a femur or tibia fracture as a single fracture to investigate the influence of single versus multiple fractures on systemic bone mass. Seventy-two adult male C57BL/6J mice underwent transverse osteotomies of the ipsilateral femur and/or tibia with subsequent internal fixation. The dynamic change of in vivo whole-body BMD was assessed at 4 days, 2 weeks, and 4 weeks after fracture. The microstructure of the L5 vertebral body and contralateral femur was assessed using micro-CT (µCT) and biomechanical tests (vertebral compression test and three-point bending test) at 2 and 4 weeks. Tartrate-resistant acid phosphatase (TRAP) staining, sequential fluorescence labeling, and systemic inflammatory cytokines were also quantified. A greater decrease in whole-body BMD was observed after multiple than single fractures. The trabecular bone volume fraction, trabecular number, and trabecular thickness of the L5 vertebral body were significantly reduced. There were no significant differences in cortical thickness, trabecular bone microstructure, or bone strength in the contralateral femur. At 4 days and 2 weeks, we observed significant increases in the serum levels of IL-6 and TNF-α. We also observed an increase in the osteoclast number of the L5 vertebral body at 4 days. These data indicate that systemic bone loss might increase with the number or severity of prior fractures, and the mechanism may be partly associated with an increased osteoclast number and a more severe inflammatory response. © 2020 American Society for Bone and Mineral Research (ASBMR).

Floating elbow combining ipsilateral distal multiple segmental forearm fractures: A case report.

BACKGROUND: Floating elbow along with ipsilateral multiple segmental forearm fracture is a rare and high-energy injury, although elbow dislocation or fracture of the ulna and radius may occur separately. CASE SUMMARY: We report the case of a 37-year-old woman with open (IIIA) fracture of the right distal humerus with multiple shaft fractures of the ipsilateral radius and ulna with a history of falling from a height of almost 20 m from a balcony. After providing advanced trauma life support, damage control surgery was performed to debride the arm wound and temporarily stabilize the right upper limb with external fixators in the emergency operating room. Subsequently, one-stage internal fixation of multiple fractures was performed with normal values of biochemical indicators and reduction in limb swelling. The patient achieved good outcome at the 7 mo follow-up. CONCLUSION: One- or two-stage treatment must be performed according to the type of injury; we efficiently used the "damage control principle."

Fetal Fractures in an Infant with Maternal Ehlers-Danlos Syndrome, CCDC134 Pathogenic Mutation and a Negative Genetic Test for Osteogenesis Imperfecta.

Intrauterine fractures are a rare clinical finding caused by abnormal early-life osteogenesis. In this case report, we reported a male infant with twenty-three intrauterine/fetal fractures resembling osteogenesis imperfecta and tested negative for COL1A1 and COL1A2 mutations. The infant's mother had Ehlers-Danlos syndrome, hypermobility type. Whole-genome sequencing revealed that there were no pathologic mutations previously documented to be associated with intrauterine fracture. Genetic mutations reported to be associated with fragility fractures were identified. These include the pathogenic homozygous mutation in the CCDC134 gene. Other genetic variants that might be responsible for variable expressivity of the skeletal manifestation include the homozygous variants of the genes CCDC134, COL15A1 and ZFPM1, and the heterozygous variants of the genes MYH3, BCHE, AUTS2. This is the first reported case of in utero fractures, that was confirmed by X-ray after birth, in an infant who had no genetic evidence for osteogenesis imperfecta, had a homozygous pathogenic mutation of an osteogenesis gene and whose mother had Ehlers-Danlos syndrome hypermobility type. Therefore, we have identified a new genetic cause for in utero fractures. If after birth, this infant were found to have these fractures in various stages of healing with a negative genetic test for osteogenesis imperfecta he would have been misdiagnosed as due to nonaccidental trauma.

Effects of emergency treatment mode of damage-control orthopedics in pelvic fracture complicated with multiple fractures.

OBJECTIVE: This study aimed to observe the application effect of emergency treatment mode of damage-control orthopedics (DCO) in pelvic fracture complicated with multiple fractures. METHODS: Ninety-four patients with pelvic fracture complicated with multiple fractures in our hospital were recruited and divided into two groups according to the random number table method, with 47 cases in each group. Patients in the control group received traditional methods for emergency treatment (early complete treatment), and patients in the research group received DCO for emergency treatment (treatment performed in stages according to patient's physiological tolerance, with simplified initial surgery, followed by ICU resuscitation, and finally definitive surgery). The two groups were compared in terms of mortality, the incidence of acidosis and hypothermia three days after the first surgery, surgery-related indexes (time of the first surgery, blood transfusion volume, intraoperative blood loss, recovery time of temperature, and length of hospital stay), coagulation function indexes (activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT) and fibrinogen (FIB)), postoperative reduction of fracture, complication rate, and quality of life. RESULTS: The incidences of acidosis, hypothermia, and mortality three days after the first surgery in the research group were lower than those in the control group (P<0.05). Compared with the control group, the research group experienced shorter time of the first surgery, less intraoperative blood transfusion volume, less intraoperative blood loss, shorter recovery time of body temperature, and shorter length of hospital stay (P<0.05). Seven days after surgery, PT, TT and APTT decreased and FIB increased in both groups (P<0.05), PT, TT and APTT in the research group were lower than those in the control group (P<0.05), while FIB was higher (P<0.05). The good rate of reduction in the research group was higher than that in the control group (P=0.025). The incidence of complications in the research group was lower than that in the control group (P=0.049). Six months after surgery, the scores of physiological function (PF), body pain (BP), role physical (RP), emotional function (EF), social function (SF), vitality, and general health (GH) of the research group were higher than those of the control group (P<0.05), but there was no significant difference in mental health (MH) between the two groups (P>0.05). CONCLUSION: The emergency treatment mode of DCO is effective in pelvic fracture complicated with multiple fractures, which can effectively improve postoperative reduction of patients, improve the coagulation function, reduce complications, and improve the quality of life.

Damage control orthopaedics in polytraumatized patients- current concepts.

The principles of fracture management in patients with multiple injuries continue to be of crucial importance. Early treatment of unstable polytraumatized patients with head, chest, abdomen or pelvic injuries, with blood loss followed by immediate fracture fixation (Early Total Care -ETC) may be associated with secondary life threatening posttraumatic systemic inflammatory response syndrome (SIRS). Development of SIRS is typically a function of the type and severity of the initial injury (the "first hit"). Immediate Fracture fixation, using reamed nails or plates, in such unstable patients with multiple injuries is subsequently defined as the "second hit" and may be associated with development of acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF), with relatively high morbidity and mortality. The other alternative for long bone fracture fixation in unstable polytraumatized patients is based on immediate treatment of life threatening conditions related to the injuries, followed by the initial use of minimally invasive modular external frames for long bone fractures and is called Damage Control Orthopedics (DCO) and is widely accepted. In order to refine the DCO concept and to avoid an overuse of external fixation, the "Safe Definitive Surgery" (SDS) concept has been introduced, which is a dynamic synthesis of both strategies (ETC and DCO). The SDS strategy employs clinical parameters and includes repeated assessment of patients. The following paper is going to summarize historical backgrounds and recent concepts in treatment of polytraumatized patients.

Modern classification and molecular-genetic aspects of osteogenesis imperfecta.

Osteogenesis imperfecta (imperfect osteogenesis in the Russian literature) is the most common hereditary form of bone fragility, it is a genetically and clinically heterogeneous disease with a wide range of clinical severity, often leading to disability from early childhood. It is based on genetic disorders leading to a violation of the structure of bone tissue, which leads to frequent fractures, impaired growth and posture, with the development of characteristic disabling bone deformities and associated problems, including respiratory, neurological, cardiac, renal impairment, hearing loss. Osteogenesis imperfecta occurs in both men and women, the disease is inherited in both autosomal dominant and autosomal recessive types, there are sporadic cases of the disease due to de novo mutations, as well as X-linked forms. The term "osteogenesis imperfecta" was coined by W. Vrolick in the 1840s. The first classification of the disease was made in 1979 and has been repeatedly reviewed due to the identification of the molecular cause of the disease and the discovery of new mechanisms for the development of osteogenesis imperfecta. In the early 1980s, mutations in two genes of collagen type I (COL1A1 and COL1A2) were first associated with an autosomal dominant inheritance type of osteogenesis imperfecta. Since then, 18 more genes have been identified whose products are involved in the formation and mineralization of bone tissue. The degree of genetic heterogeneity of the disease has not yet been determined, researchers continue to identify new genes involved in its pathogenesis, the number of which has reached 20. In the last decade, it has become known that autosomal recessive, autosomal dominant and X-linked mutations in a wide range of genes, encoding proteins that are involved in the synthesis of type I collagen, its processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells, cause imperfect osteogenesis. A large number of causative genes complicated the classical classification of the disease and, due to new advances in the molecular basis of the disease, the classification of the disease is constantly being improved. In this review, we systematized and summarized information on the results of studies in the field of clinical and genetic aspects of osteogenesis imperfecta and reflected the current state of the classification criteria for diagnosing the disease.