Comparative study of different extendable intramedullary rods combined with surgery in the treatment of congenital pseudarthrosis of the tibia.

BACKGROUND: When using traditional extensible intramedullary rods to treat congenital pseudarthrosis of the tibia (CPT), there were cases of re-fracture and internal fixation fracture. Therefore, the authors propose a research hypothesis that a thicker distal extensible intramedullary rod can better protect the tibia and reduce the incidence of refracture PURPOSE: To investigate the clinical efficacy of new and traditional extensible intramedullary rods in the treatment of CPT in children METHODS: From January 2017 to December 2021, the clinical data of 49 children with CPT who were treated with traditional extensible intramedullary rod combined surgery (group A) and new extensible intramedullary rod combined surgery (group B) in our hospital were collected. Inclusive criteria: ① Crawford type IV CPT children; ② The operation was performed by the same team. EXCLUSION CRITERIA: patients with multiple tibial angulation. During follow-up, the initial healing, proximal tibial valgus, tibial length, ankle valgus, refracture and intramedullary rod displacement of CPT children in the two groups were evaluated RESULTS: It was a retrospective investigation. In group A, 26 cases met the inclusion criteria, 24 cases achieved primary healing, with an primary healing rate of 92%, including 1 case of nonunion due to osteomyelitis complications after surgery, and 1 case of delayed healing, with an average healing time of 4.7 ± 0.8 months. 17 cases (68%) had unequal tibia length, with an average difference of 1.6 ± 0.8 cm. Ankle valgus occurred in 10 cases (40%) with an average of 14.4°±4.8°; Proximal tibial valgus occurred in 6 cases (24%) with an average of 7 °± 1.8 °. 20 cases (80%) had tip of the rod migration.10 cases (40%) had re-fracture; The average follow-up time was 2.4 ± 0.4 years. In group B, 22 patients achieved primary healing, and the primary healing rate was 95%, including 1 case with delayed healing. The average healing time was 4.7 ± 1.7months. 14 cases (61%) had unequal tibia length, with an average difference of 1 ± 0.5 cm. Ankle valgus occurred in 4 cases (17%) with an average of 12.3 °±4.9°; The proximal tibia valgus occurred in 9 cases (39%), with an average of 7.7 °±2.5 °. 14 cases (61%) had new type of intramedullary rod displacement. 3 cases (13%) had re-fracture; The average follow-up time was 2.3 ± 0.6years CONCLUSION: Compared with the traditional extended intramedullary rod combined operation, the new type of extended intramedullary rod combined operation has a lower incidence of re-fracture after CPT, but it still needs to be verified by large sample and multi-center research.

Visible-Light-Triggered Difluoroacetylation/Cyclization of Chromone-Tethered Alkenes Enabling Synthesis of Tetrahydroxanthones.

Hydroxanthones have attracted considerable attention due to their significance in organic and biological chemistry, yet their synthesis remains a great challenge. In this study, a series of chromone-tethered alkenes are designed, and a radical cyclization reaction of these chromone derivatives has been achieved under photoredox conditions. The reaction uses bromodifluoroacetamides or bromodifluoroacetates as coupling partners, affording a broad range of functionalized tetrahydroxanthone products with up to 85% yields. The reaction is triggered via the generation of difluoroacetate radicals or alkene radical cations with fac-Ir(ppy)3 or 2,3,5,6-tetrakis(carbazol-9-yl)-1,4-dicyanobenzene as a photocatalyst. This approach offers access to various tetrahydroxanthone derivatives from readily available starting materials and enriches the research content of heteroarene-tethered alkenes.

Copper-catalyzed multicomponent reaction of ß-trifluoromethyl ß-diazo esters enabling the synthesis of ß-trifluoromethyl N,N-diacyl-ß-amino esters.

An efficient multicomponent reaction of newly designed ß-trifluoromethyl ß-diazo esters, acetonitrile, and carboxylic acids via an interrupted esterification process under copper-catalyzed conditions has been developed, which affords various unsymmetrical ß-trifluoromethyl N,N-diacyl-ß-amino esters in good to excellent yields. The reaction features mild conditions, a wide scope of ß-amino esters and carboxylic acids, and also applicability to large-scale synthesis, thus providing an efficient way for the synthesis of ß-trifluoromethyl ß-diacylamino esters. Furthermore, this reaction represents the first example of a Mumm rearrangement of ß-trifluoromethyl ß-diazo esters.

The Duration of Hardware Retention After Radiologic Union of Surgically Treated Femoral Neck Fractures in Children May Predict the Aggravation or Occurrence of Avascular Necrosis of the Femoral Head or Neck After Hardware Removal.

BACKGROUND: The incidence of aggravation or occurrence of avascular necrosis (AVN) following hardware removal in surgically treated pediatric femoral neck fractures who achieved radiologic consolidation is unknown. This study aimed to investigate the risk factors for this complication. METHODS: Seventy-one pediatric (mean age: 9.8±3.9 y) were retrospectively analyzed. Risk factors (age, sex, laterality, severity of initial displacement, type of fracture, time from trauma to reduction, reduction and fixation method, quality of reduction, time required to achieve radiologic union, duration of hardware retention, presence of AVN before hardware removal and follow-up time) were recorded. The severity of AVN was assessed based on radiographs with Ratliff's classification. RESULTS: Following hardware removal, the aggravation/occurrence of AVN was detected in 11 hips (15.5%). Among the 5 hips (7%) with aggravation of AVN, 1 (1.4%) with type II AVN and 3 (4.2%) with type III AVN exhibited aggravation of type I AVN, while the remaining hip (1.4%; type I) showed enlargement of the involved AVN area. Six hips (8.5%) developed AVN following hardware removal: 2 (2.8%) were classified as type I and 4 (5.6%) as type III. Receiver operating characteristic curve analysis indicated that hardware retention >7 months after union is associated with a decreased rate of aggravation or occurrence of AVN of the femoral neck or head following hardware removal. CONCLUSIONS: The incidence of aggravation or occurrence of AVN following hardware removal in surgically treated pediatric femoral neck fractures is 15.5%; hardware retention >7 months after radiologic union may reduce the risk of aggravation or occurrence of AVN of the femoral neck or head postimplant removal. LEVEL OF EVIDENCE: Level III.

Is there an alternative to the Delbet-Colonna classification? Introduction and reliability assessment of a new classification system for paediatric femoral neck fractures: preliminary results.

PURPOSE: The purpose of this study was to introduce a new classification system for paediatric femoral neck fractures (PFNFs) and to evaluate its reliability. METHODS: Two hundred and eight unilateral PFNFs (mean patient age: 9.0 ± 4.8 years) were included. Based on preoperative radiographs, the new classification system distinguished PFNFs without anterior or posterior translation (Type I), PFNFs with anterior (Type II) or posterior (Type III) translation, PFNFs with a comminuted medial or posterior column (Type IV), and subtrochanteric femoral fractures (SFFs; Type V). Radiographs were evaluated twice with an interval of two weeks by 19 raters with different specialties, experiences and geographical origins. The results were compared with a selection of 50 patient age-matched unilateral PFNFs and SFFs (mean patient age: 9.1 ± 4.9 years). These were graded twice by the same graders according to the Delbet-Colonna (D-C) classification. RESULTS: Four radiologists and 15 paediatric orthopaedic surgeons from Europe and Asia graded the radiographs. Fair agreement was found between radiologists (κ = 0.296 ± 0.01) and surgeons (κ = 0.3 ± 0.005) (P = 0.17), although more experienced surgeons performed better than less experienced ones; a similar fair assessment was found for raters from Europe (κ = 0.309 ± 0.021) and Asia (κ = 0.3 ± 0.006) and for type II, III and IV fractures; the κ value in the first evaluation (0.309) was similar to that in the second evaluation (0.298). The overall κ value of the D-C classification subtypes was significantly higher (0.599 ± 0.217) than that of the new classification, 0.326 ± 0.162 (t = 3.190 P = 0.005). CONCLUSIONS: The new classification system showed fair reliability relative to the D-C classification. The reliability of the new classification system was not affected by the specialty or geographic origin of the rater or the evaluation round, only by rater experience level. The concordance was worse for PFNFs with anterior or posterior translation or with a comminuted medial or posterior columns.

Physeal bar resection by modified arthroscopically assisted surgery in a closed osteocavity.

Background: Physeal bar resection has been used for partial growth arrest treatment for a decade while removing the bony bar minimally invasively and accurately is challenging. This research aims to illustrate a modified arthroscopically assisted surgery, by which all the procedure was under all-inside visualization, without the constant exchange between burring under fluoroscopy, followed by irrigation, suction, and arthroscopy of the canal. Methods: We retrospectively reviewed the patients who sustained physeal bar resection under direct all-inside visualization of the arthroscope during 2016-2021. Patients who underwent physeal bar resection with the aid of an arthroscope for identifying the physeal cartilage but not resecting and visualizing the physeal bar simultaneously were excluded from this study. Results: In total, nine patients with ten related joints were included in this study. All the patients were followed up for at least two years. The average following time was 28.5 ± 6.7 months. Eight patients with nine related joints had an improvement of angular deformity, averaging 8.3 ± 6.9 degrees, and one had a worsening of the angular deformity. All the patients had a leg length discrepancy improvement, while four patients still had LLD >1 cm. The surgery time was 3.1 ± 0.7 h. There were no postoperative fractures, infections, or intraoperative complications such as neurovascular injury. Conclusions: Using clamps to form a closed osteocavity could make physeal bar resection under all-inside arthroscopic visualization feasible, which is minimally invasive, accurate, and safe.

Circ_0000888 regulates osteogenic differentiation of periosteal mesenchymal stem cells in congenital pseudarthrosis of the tibia.

Congenital pseudarthrosis of the tibia (CPT) is a refractory condition characterized by the decreased osteogenic ability in tibial pseudarthrosis repair. Periosteal mesenchymal stem cells (PMSCs) are multipotent cells involved in bone formation regulation. However, the mechanisms underlying its role in CPT remain unclear. In this study, we observed downregulation of circ_0000888 and pleiotrophin (PTN), as well as upregulation of miR-338-3p in CPT derived PMSCs (CPT-dPMSCs). Our results demonstrated that circ_0000888 and PTN likely enhanced the viability, proliferation, and osteogenic ability of PMSCs, while miR-338-3p had the opposite effect. Further analysis confirmed the regulatory relationship circ_0000888 suppressed the activity of miR-338-3p and upregulated the expression of its downstream target PTN by binding to miR-338-3p, consequently promoting the viability and osteogenic differentiation ability of CPT-dPMSCs. Our findings unveil an unexpected link between circ_0000888/miR-338-3p/PTN in promoting osteogenic ability and indicate the potential pathogenic mechanisms of CPT.

Cascade Detrifluoroacetylation, C-S Bond Cleavage, and SN2' Reaction of α,α-Difluorinated Gem-Diols with MBH Esters.

A new SN2' reaction type of Morita-Baylis-Hillman (MBH) ester with sulfonyl anion, generated in situ via detrifluoroacetylation as a nucleophile is developed. Experimental results and DFT calculations disclose that the reaction proceeds via C-C bond cleavage to generate a PhSO2CF2 anion, C-S bond cleavage to generate a sulfonyl anion with the release of CF2 carbene, and an SN2' reaction with the MBH ester. The reaction features operational simplicity, wide substrate scope, high yields, and excellent stereoselectivity, which represents a new reaction mode of fluorinated gem-diols and also provides an efficient way to obtain ß,γ-unsaturated sulfones.

A Cu-promoted reaction of ß-keto trifluoromethyl amines enabling stereoselective synthesis of trifluoromethylated aziridines.

An efficient Cu(I) complex-promoted intramolecular cyclization reaction of ß-keto trifluoromethyl amines has been developed, providing access to a series of unprotected trifluoromethylated aziridines with good chemical yields and excellent stereoselectivity (trans : cis > 99 : 1). The reaction can be carried out under mild conditions and tolerates a wide range of substrates with diverse functional groups, representing a straightforward method for the preparation of trifluoromethylated aziridines from readily available starting materials.

Research on anterior minimally invasive approach in the treatment of children with developmental dysplasia of the hip.

OBJECTIVES: To investigate the clinical efficacy and safety of open reduction through anterior minimally invasive approach in the treatment of children with developmental dysplasia of the hip. METHOD: A total of 23 patients (25 hips) less than 2 years with developmental dysplasia of the hip treated by open reduction through anterior minimally invasive approach were treated in our hospital from August 2016 to March 2019. Through the anterior minimally invasive approach, we enter from the gap between sartorius muscle and tensor fasciae lata without cutting off rectus femoris muscle, which can effectively expose the joint capsule and reduce the damage to medial blood vessels and nerves. The operation time, incision length, intraoperative bleeding, hospital stay and surgical complications were observed. The progression of developmental dysplasia of the hip and avascular necrosis of the femoral head were evaluated by imaging examination. RESULT: All patients were performed with follow-up visit for an average of 22 months. The average incision length was 2.5 cm, the average operation time was 26 min, the average intraoperative bleeding was 12ml, and the average hospital stay was 4.9 days. All patients received concentric reduction immediately after operation, and no re-dislocation occurred. At the last follow-up visit, the acetabular index was (25.8 ± 6.4°). During the follow-up visit, X-ray showed avascular necrosis of the femoral head in 4 hips (16%). CONCLUSION: open reduction through anterior minimally invasive approach can achieve good clinical effect in the treatment of infantile developmental dysplasia of the hip.

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups.

A synthetic route to the bench-stable fluorinated masked carbene reagent diethyl 2-diazo-1,1,3,3,3-pentafluoropropylphosphonate, bearing a trifluoromethyl and a difluoromethyl group is reported for the first time. Its application in CuI-catalyzed cyclopropanation reactions with aromatic and aliphatic terminal alkenes under mild reaction conditions is demonstrated. In total, sixteen new cyclopropanes were synthesized in good to very good yields.

New Approved Drugs Appearing in the Pharmaceutical Market in 2022 Featuring Fragments of Tailor-Made Amino Acids and Fluorine.

The strategic fluorination of oxidatively vulnerable sites in bioactive compounds is a relatively recent, widely used approach allowing us to modulate the stability, bio-absorption, and overall efficiency of pharmaceutical drugs. On the other hand, natural and tailor-made amino acids are traditionally used as basic scaffolds for the development of bioactive molecules. The main goal of this review article is to emphasize these general trends featured in recently approved pharmaceutical drugs.

Synthesis of Aminoalkyl Sclareolide Derivatives and Antifungal Activity Studies.

Sclareolide was developed as an efficient C-nucleophilic reagent for an asymmetric Mannich addition reaction with a series of N-tert-butylsulfinyl aldimines. The Mannich reaction was carried out under mild conditions, affording the corresponding aminoalkyl sclareolide derivatives with up to 98% yield and 98:2:0:0 diastereoselectivity. Furthermore, the reaction could be performed on a gram scale without any reduction in yield and diastereoselectivity. Additionally, deprotection of the obtained Mannich addition products to give the target sclareolide derivatives bearing a free N-H group was demonstrated. In addition, target compounds 4-6 were subjected to an antifungal assay in vitro, which showed considerable antifungal activity against forest pathogenic fungi.

Electrochemical Annulation of Indole-Tethered Alkynes Enabling Synthesis of Exocyclic Alkenyl Tetrahydrocarbazoles.

An electrochemical sulfonylation-triggered cyclization reaction of indole-tethered terminal alkynes with sulfinates as sulfonyl sources has been developed, which affords exocyclic alkenyl tetrahydrocarbazoles in good chemical yields. This reaction features convenient operation and tolerates a wide scope of substrates with a variety of electronically and sterically diverse substituents. Furthermore, high E-stereoselectivity is observed for this reaction, which provides an efficient method for the preparation of functionalized tetrahydrocarbazole derivatives.

Association between preoperative concurrent fibular pseudarthrosis and risk of postoperative ankle valgus in patients with congenital pseudarthrosis of the tibia.

BACKGROUND: This study evaluated the correlation of preoperative concurrent fibular pseudarthrosis with the risk of ankle valgus deformity in patients with congenital pseudarthrosis of the tibia (CPT) who underwent successful surgical treatment. METHOD: The children with CPT who were treated at our institution between 1 January 2013 and 31 December 2020 were retrospectively reviewed. The independent variable was preoperative concurrent fibular pseudarthrosis, and the dependent variable was postoperative ankle valgus. Multivariable logistic regression analysis was performed after adjusting for variables that might affect the risk of ankle valgus. Subgroup analyses with stratified multivariable logistic regression models were used to assess this association. RESULTS: Of the 319 children who underwent successful surgical treatment, 140 (43.89%) developed ankle valgus deformity. Moreover, 104 (50.24%) of 207 patients with preoperative concurrent fibular pseudarthrosis developed an ankle valgus deformity compared with 36 (32.14%) of 112 patients without preoperative concurrent fibular pseudarthrosis (p=0.002). After adjusting for sex, body mass index, fracture age, age of patient undergoing surgery, surgery method, type 1 neurofibromatosis (NF-1), limb-length discrepancy (LLD), CPT location and fibular cystic change, patients with concurrent fibular pseudarthrosis presented a higher risk of ankle valgus than those without concurrent fibular pseudarthrosis (OR 2.326, 95% CI 1.345 to 4.022). This risk further increased with CPT location at the distal one-third of the tibia (OR 2.195, 95% CI 1.154 to 4.175), age <3 years of patient undergoing surgery (OR 2.485, 95% CI 1.188 to 5.200), LLD <2 cm (OR 2.478, 95% CI 1.225 to 5.015) and occurrence of NF-1 disorder (OR 2.836, 95% CI 1.517 to 5.303). CONCLUSION: Our results indicate that patients with CPT and preoperative concurrent fibular pseudarthrosis have a significantly increased risk of ankle valgus compared with those without preoperative concurrent fibular pseudarthrosis, particularly in those with CPT location at the distal third, age <3 years at surgery, LLD <2 cm and NF-1 disorder.

Is physeal distraction osteogenesis a good choice to treat CPT patients with tibial shortening?

The purpose of this study was to evaluate the healing index and complications of distraction osteogenesis through the physis in children with Congenital pseudarthrosis of the tibia (CPT) using Ilizarov external fixation device. Nine children with CPT who underwent distraction osteogenesis through the physis surgery with an Ilizarov external fixation device between June 2018 and August 2020 were included in the study. The average follow-up time was 36.1 months. X-ray examination was performed 1 month after physis lengthening, and the callus quality was evaluated using the Li classification. Any complications and the quality of the callus after tibial lengthening were followed up. The average age at the time of operation was 9.4 years, and the average follow-up time was 36.1 months. The average lengthening length of children with CPT was 6.6 cm. The incidence of good callus morphology was 100%, and the healing index was 51.1 d/cm. The average fixation time of the external fixation device was 316 days. Needle tract infection occurred in one case, ankle stiffness occurred in one case, ankle plantar flexion 20° deformity occurred in one case, angular deformity of the tibial lengthening segment occurred in one case (7°) and limited movement of knee joint occurred in one case (0-20°-70°). The osteogenic quality of the patients of distraction osteogenesis through the physis with tibial shortening and small diameter of the proximal tibia is good, which provides a choice of operation for the children with CPT.

A modified pixel value ratio based on contralateral normal bone: a novel reliable indicator for distraction osteogenesis.

BACKGROUND: The traditional pixel value ratio (tPVR) is subject to disuse osteopenia of the adjacent bone in distraction osteogenesis (DO). Therefore, a modified PVR (mPVR) based on the contralateral normal bone was developed and validated to address this issue. METHODS: A total of 79 bone lengthening subjects were recruited in this retrospective study. The difference between the mPVR and tPVR of early callus was identified in the first three months after osteotomy. Moreover, we further investigated the relationship between mPVR and healing index (HI), lengthening index (LI) and external fixator index (EFI). Finally, the potential influencing factors for mPVR of the early callus were analyzed. RESULTS: The mPVR was significantly lower than the tPVR in the first three months after osteotomy, and the difference gradually increased. Interestingly, the mPVR of the early callus in the first two months was negatively correlated with the HI, LI and EFI. Moreover, the age, lengthening site, total bilirubin and mean hemoglobin content were associated with the mPVR of early callus during DO. CONCLUSION: The mPVR based on contralateral normal bone is a novel reliable indicator for DO, which may be helpful for the clinical management of DO. However, the findings of this study need to be confirmed further by larger prospective research.

Differential expression and effect analysis of lncRNA-mRNA in congenital pseudarthrosis of the tibia.

Background: To analyze the lncRNA-mRNA differential expression and co-expression network of periosteal stem cells (PSCs) from congenital pseudarthrosis of the tibia (CPT) and normal patients, and to explore the role of key lncRNAs. Methods: Differentially expressed lncRNAs and mRNAs in PSCs were obtained by sequencing, and biological functions of differentially expressed mRNAs were detected by gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway and protein -protein interaction (PPI) analysis. The co-expression network of lncRNA-mRNA was constructed by correlation analysis of differentially expressed lncRNAs and mRNAs, and the key lncRNAs were screened according to the connectivity degree. After that, the cis-regulated target genes of differential expressed lncRNAs and mRNAs were predicted. Results: A total of 194 differentially expressed lncRNAs were identified, including 73 upregulated and 121 downregulated genes. A total of 822 differentially expressed mRNAs were identified, including 311 upregulated and 511 downregulated genes. GO, KEGG and PPI enrichment analysis showed that the regulatory function of differentially expressed mRNAs were mainly gathered in skeletal system development and tissue morphogenesis. The co-expression network with 226 nodes and 3,390 edges was constructed based on correlation analysis. A total of 10 key lncRNAs, including FAM227B, POM121L9P, AF165147 and AC103702, were screened according to connectivity degree. Prediction of target genes indicated that FAM227B-FGF7 and AC103702-HOXB4/5/6 may play an important role in the pathogenesis of CPT. Conclusion: A total of 10 key lncRNAs, including FAM227B, POM121L9P, AF165147, and AC103702, occupy the core position in the co-expression network, suggesting that these lncRNAs and their target genes may play an important role in the pathogenesis of CPT.

Clinical study of a new type of telescopic rod for the treatment of congenital pseudarthrosis of the tibia in children.

The purpose of this study was to investigate the initial efficacy of a new telescopic rod in the treatment of congenital pseudarthrosis of tibia (CPT) in children. A new type of telescopic rod for children was designed and its clinical results were evaluated. There were nine cases of CPT on the right and six cases on the left; there were six females and nine males. The average age at operation was 35.5 months. There were 12 cases with neurofibromatosis type 1 and 4 cases with proximal tibial dysplasia. The initial healing of tibial pseudarthrosis, proximal tibial valgus deformity, tibial length, ankle valgus, ankle function, and intramedullary rod displacement were evaluated during follow-up. All 15 cases were followed up for an average of 18.2 months, 14 cases achieved initial healing, with an average healing time of 4.3 months. Ten cases had unequal lengths of the tibia, with an average of 0.9 cm. Proximal tibial valgus occurred in seven cases and ankle valgus occurred in one child. The average range of motion of the ankle joint was 23° and the average plantar flexion was 42°. The average extension of the new telescopic rod was 1.6 cm. The displacement of the telescopic rod occurred in seven cases, there was no epiphyseal plate tethering and re-fracture. The new children's telescopic rod has a reasonable design and can extend with the growth of tibia. There are no complications of epiphyseal plate tethering and re-fracture. It provides a new choice of intramedullary fixation for the treatment of CPT.