Short Bones Research Articles

Hypophosphatemic rickets in an Italian multicentric cohort of 24 subjects: a clinical and molecular characterisation.

Rickets is a rare bone disorder due to altered calcium, vitamin D, and phosphorus metabolism, caused by nutritional deficiencies or, in 13% of cases, genetic origin. Few data are available on an Italian cohort of rickets. Twenty-four patients with confirmed low serum phosphorus levels and reduced renal tubular phosphate reabsorption were recruited from different tertiary care centres over the last 5 years. Biochemical, clinical, and anamnestic data were also collected. DNA was extracted and subjected to targeted next-generation sequencing. Twenty-four single-nucleotide variants were identified in the PHEX (eight pathogenic, five likely pathogenic, three variants of uncertain significance), CYP27B1 (two pathogenic, four likely pathogenic), and SLC34A3 (one pathogenic, one likely pathogenic) genes. Five large genomic deletions involving one or more PHEX exons were detected. Eight of 20 PHEX and both SLC34A3 variants were novel, and segregation analysis identified 11 familial and three de novo cases. Biochemical data confirmed high serum alkaline phosphatase and low 25-hydroxyvitamin D3 levels, whereas the main clinical manifestations were short stature (76.1%), bone deformities (85.7%), musculoskeletal pain (71.4%), and muscle weakness (55.5%). Our study provides clinical and genetic descriptions of rickets in a cohort of Italian patients. Moreover, we expanded the spectrum of mutations associated with the genetic forms of this disorder and suggested a high-throughput sequencing approach to provide a molecular diagnosis for adequate follow-up of patients.

A novel missense pathogenic variants of TMEM53 in an Iranian family with craniotubular dysplasia, Ikegawa type.

Craniotubular dysplasia, Ikegawa type (CTDI) is a rare autosomal recessive skeletal dysplasia characterized by hyperostosis of the calvaria and skull base, metadiaphyseal undermodeling of the long tubular bones, and mild shortening and diaphyseal broadening of the short tubular bones. Its causal gene is TMEM53. Six CTDI families have been reported; however, its clinical course and prognosis still remain to be determined. Here, we report two Iranian siblings carrying a novel homozygous missense variant of TMEM53. The affected individuals were referred for progressive severe visual loss of unknown cause. The patient had severe optic atrophy and optic canal narrowing. Radiographic evaluation suggested the diagnosis of CTDI, which was confirmed by the identification of TMEM53 variant (c.704G > T, p.R235L) co-segregating in the consanguineous family. The proband underwent trans-nasal endoscopic optic canal decompression and showed remarkable improvement in visual acuity and daily visual tasks. We recommend early comprehensive clinical and genetic evaluation followed by proper treatment to improve the prognosis of CTDI.

Foetal Achondroplasia: Prenatal Diagnosis, Outcome and Perspectives

BackgroundAchondroplasia, due to a specific pathogenic variant in FGFR3, is the most common viable skeletal dysplasia and the diagnosis is mostly done in the prenatal period. Since 2021, the use of Vosoritide, a specific treatment for achondroplasia, validated in phase 3 placebo-controlled trials, has been recommended to significantly increase the height of children and infants. In the light of these new therapeutic prospects, a complete understanding of the pathophysiology of skeletal damages occurring from foetal life is required. ObjectivesTo describe foetal imaging and the antenatal and postnatal management of pregnancies complicated by a diagnosis of foetal achondroplasia. MethodsA retrospective and descriptive study, including all pregnant women with a prenatal diagnosis of achondroplasia, was conducted in the prenatal unit of Necker Hospital (Paris, France) between 2009 to 2022. Maternal and obstetric characteristics and foetal imaging (ultrasound and bone CT) were collected. Pregnancy outcomes, paediatric follow-up in the case of live births, and post-mortem examination (PME) data in the case of termination of pregnancy were reported. In addition, we have prospectively developed a specific research protocol using foetal brain MRI to assess the anatomy of the foramen magnum, following the same approach currently recommended in the postnatal period. Results29 cases of achondroplasia were included. Median gestational age at referral was 31+2 weeks’, about 1 week after the suspected diagnosis on routine ultrasound. Shortening of the femoral length and of all the other long bones, macrocephaly, facial abnormalities, increased metaphyseal-diaphyseal angle and tapering of the proximal femoral bone were the five most prevalent ultrasound signs. Foetal diagnosis was done by the identification of the foetal FGFR3 mutation and/or by CT scans (n=15) where specific abnormalities of the long bones, platyspondyly and abnormal profile have been described in 100% of cases. PME revealed: i) on external examinations (n=7) that all fetuses had very short long bones, moderate platyspondyly, small iliac wings with internal spines, macrocrania, and narrow thorax, ii) on internal examination (n=5) all had severe abnormalities in the growth plate and particularities in the temporal cortex and hippocampal region. One foetal MRI was performed at 33 weeks’ and revealed tight stenosis of the foramen magnum and compression of the spinal cord. Of the live-born infants for whom follow-up was known (n=6), 2/6 (including the case who had a foetal MRI) required neurosurgical intervention in the first few months of life for spinal cord compression due to severe stenosis of the foramen magnum. ConclusionA complete mapping of the skeletal features present in fetuses with achondroplasia is reported here, providing a better understanding of the pathophysiology of this condition. New tools such as foetal MRI, to assess the risk of postnatal severe neurological complications, could help improve the care pathway of the affected neonates.

Combined ADAMTS10 and ADAMTS17 inactivation exacerbates bone shortening and compromises extracellular matrix formation.

Weill-Marchesani syndrome (WMS) is characterized by severe short stature, short hands and feet (brachydactyly), joint contractures, tight skin, and heart valve, eye, and skin anomalies. Whereas recessive WMS is caused by mutations in ADAMTS10 , ADAMTS17 , or LTBP2 , dominant WMS is caused by mutations in FBN1 (encoding fibrillin-1). Since bone growth is driven by chondrocyte proliferation and hypertrophy in the growth plates, the genetics of WMS suggests that the affected ECM proteins act within the same pathway to regulate chondrocyte and growth plate function. Here, we investigated the role of the secreted ADAMTS proteases ADAMTS10 and ADAMTS17 in growth plate function and ECM formation. We generated Adamts10 ; Adamts17 double knockout (DKO) mice, which showed significant postnatal lethality compared to single Adamts10 or Adamts17 KO mice. Importantly, we observed severe bone shortening DKO mice, which correlated with a narrower hypertrophic zone in their growth plates. ADAMTS17 substrates identified by N-terminomics and yeast two-hybrid screening identified the ECM proteins fibronectin and collagen VI (COL6). However, validation experiments did not reveal direct proteolysis of either fibronectin or COL6 by ADAMTS17. We then investigated ECM formation in primary ADAMTS10- and ADAMTS17-deficient skin fibroblasts and observed compromised fibronectin deposition concomitant with aberrant intracellular accumulation of fibrillin-1. These findings support a role for ADAMTS17 in ECM protein secretion and assembly. Collectively, our data suggest that ADAMTS10 and ADAMTS17 regulate bone growth by regulating chondrocyte hypertrophy or hypertrophic chondrocyte turnover. Mechanistically, ADAMTS17 appears to be a critical regulator of ECM protein secretion or pericellular matrix assembly, whereas ADAMTS10 likely modulates ECM formation at later stages, possibly regulating the spatio-temporal deposition of fibrillin isoforms.

Comparison of the natural course of clinical and radiologic features in 13 patients with TRPV4-related skeletal dysplasias.

Heterozygous TRPV4 mutations cause a group of skeletal dysplasias characterized by short stature, short trunk, and skeletal deformities. The aim of this study is to compare the natural history of clinical and radiologic features of patients with different TRPV4-related skeletal dysplasias. Thirteen patients with a mutation in TRPV4 were included in the study, and 11 were followed for a median of 6.5 years. The clinical phenotype of five patients was compatible with spondylometaphyseal dysplasia Kozlowski type, three each with metatropic dysplasia and brachyolmia type 3, and one each with spondyloepiphyseal dysplasia Maroteaux type and congenital distal spinal muscular atrophy. Short stature and bone pain when running, walking, and climbing stairs occurred in patients with spondylometaphyseal dysplasia Kozlowski type and metatropic dysplasia from the age of 5 years and worsened with increasing age. Kyphosis was more pronounced with increasing age in these two groups of patients, while severe scoliosis occurred in brachyolmia type 3. In the radiographs of patients with spondylometaphyseal dysplasia Kozlowski type and metatropic dysplasia, severe platyspondyly persisted into adulthood or puberty. The patients with spondylometaphyseal dysplasia Kozlowski type exhibited irregular proximal femora leading to destruction of the femoral head towards the end of puberty, whereas metatropic dysplasia showed marked irregularity and widening of the femoral neck. We also observed that metaphyseal dysplasia in long bones other than the proximal femur was so inconspicuous that it could be ignored in patients with spondylometaphyseal dysplasia Kozlowski type. Comparison of radiologic features that change with age in five different TRPV4-related skeletal dysplasias will be of great benefit in the management of this patient group.

Clinical, Radiographic, and Molecular Analysis of Patients with X-Linked Hypophosphatemic Rickets: Looking for Phenotype-Genotype Correlation.

X-linked hypophosphataemic rickets (XLH) represents the most frequent type of rickets from genetic origin, it is caused by mutations on the PHEX gene. The main clinical manifestations are short stature and bone deformities. Phenotype variation is observed at the intrafamily and interfamily level. The bases for this variation are not fully understood. The aim of this study was to investigate if there is a phenotype-genotype correlation in a cohort of patients with confirmed diagnosis of XLH. We recruited a total of 130 patients of Mexican Mestizo origin with confirmed molecular diagnosis of XLH; this is one of the largest cohorts reported. Radiographies for calculating the rickets severity score (RSS) were available from 50 patients. A total of 56 different pathogenic variants were found among the study population; from them, 31 variants have not been previously reported. We compared the RSS values between individuals considering clinical and biochemical characteristics such as age, height, sex, phosphorus, and alkaline phosphatase in serum; no significant differences were observed. Then, we compared the RSS considering if the variant was intronic or exonic and considering the presence of a truncated protein or not. None of the two comparisons showed significant differences. We did not find a genotype-phenotype correlation in the study population. Despite the knowledge regarding the genetic cause of XLH, the mechanisms driving the intrafamily and interfamily variability remain elusive. More analyses looking for the genotype-phenotype correlation are necessary in other populations, especially considering the discovery of new mutations in patients from different origin.

Endoplasmic reticulum stress causes long bone shortening in P4hbC402R/+ mice: A mouse model exhibiting significant features of cole-carpenter syndrome driven by P4HB mutations.

Cole-Carpenter syndrome (CCS) is a rare autosomal-dominant genetic disease characterized by craniosynostosis, ocular proptosis, hydrocephalus, distinctive facial features, and bone fragility. Previous cases of CCS are associated with genetic variations in P4HB, which encodes the protein disulfide isomerase (PDI), a key enzyme in protein folding. Patients with CCS caused by P4HB mutations often present with short stature, limb deformities, and abnormal epiphyseal plates. However, the underlying mechanisms are largely unknown. To investigate this, a mouse model expressing the P4hbC402R mutation (corresponding to P4HBC400R in humans) was generated. Although the mouse model did not exhibit craniofacial bone defects or brittle bone phenotypes, it did show significantly shortened long bones-a prominent characteristic of P4HB-induced CCS. This was due to impaired proliferation and delayed hypertrophy of growth plate chondrocytes. Mutant PDI was found to accumulate abnormally in the endoplasmic reticulum (ER), and in vitro experiments revealed defects in both the catalytic and chaperone activities of mutant PDI. In addition, we observed enhanced ER stress and activation of the PKR-like ER kinase (PERK) pathway in P4hbC402R/+ chondrocytes. Inhibition of ER stress mitigated PERK activation, alleviated defective chondrocyte proliferation and differentiation, thereby rescuing bone length. Taken together, enhanced ER stress and the activation of the PERK, potentially initiated by the malfunctioning of PDIC402R or its abnormal accumulation within the ER, or both, lead to compromised chondrocyte proliferation and differentiation in mice, and ultimately stunts mice growth. This provides new insights into the pathogenesis of P4HB-dominated CCS and offers potential therapeutic targets.

Metatarsal Aneurysmal Bone Cysts Treated With En Bloc Resection and Reconstruction With Fibular Allograft.

Treatment of Primary metatarsal aneurysmal bone cyst (ABC) with curettage and bone grafting unfortunately has a high recurrence rate, particularly in short tubular bones. This study presents a 16-year experience treating ABCs in the bones of the foot at an orthopaedic oncology referral center. Treatment involved en bloc resection and reconstruction of the defect with fibular allograft in all cases. Retrospectively collected data were used to document the outcomes. This retrospective review includes patients with primary metatarsal ABC treated en bloc resection at a single center between 2004 and 2020. Information on the diagnosis, treatment, complications, and outcomes was collected from our database for all eligible patients. Radiologic healing was used as our primary outcome measure. The patient's function was assessed using the Toronto Extremity Salvage Score (TESS) and Musculoskeletal Tumor Society (MSTS) score. The study included 19 subjects (11 women, 8 men) with a mean age of 18 years (SD 11-35). The average resected length was 4.24 cm (3-6 cm). The mean follow-up time was 79.26 months (28-160 months). The mean TESS score and MSTS were 94.52 and 28.42, respectively. The average healing time was 10.2 weeks. No patient had local recurrence. Arthrodesis was performed in 3 patients because of joint involvement. Repeat surgery was performed for 2 patients, debridement for one because of infection and bone graft for another because of nonunion. One patient had experienced an allograft fracture. Based on the Enneking classification, our experience has shown that a reasonable surgical approach for primary active and invasive metatarsal ABC is en bloc resection and reconstruction with fibula allograft. This method has a low risk of recurrence and does not result in significant functional impairment.

Optimizing bone transport strategies: a pixel value ratio-based evaluation of regeneration rates in bifocal and trifocal techniques

BackgroundBone transport techniques are crucial for managing large bone defects, but the optimal approach for different defect lengths remains unclear. This study aimed to compare bone regeneration rates between short bifocal bone transport (SBBT), long bifocal bone transport (LBBT), and trifocal bone transport (TBT) using pixel value ratio (PVR) as an objective quantitative measure.MethodsThis retrospective study included 60 patients undergoing lower limb bone transport, divided into SBBT (n = 22, defects <6 cm), LBBT (n = 20, defects ≥6 cm), and TBT (n = 18, defects ≥6 cm) groups. PVR was measured at 4, 8, and 12 weeks postoperatively using standardized digital radiographs. Healing index (HI) and external fixation index (EFI) were calculated to assess treatment efficiency. Demographic data, surgical characteristics, and complications were also analyzed.ResultsTBT showed significantly higher PVR values compared to LBBT at all time points (4 weeks: 0.779 ± 0.036 vs. 0.719 ± 0.027, p < 0.001; 8 weeks: 0.822 ± 0.027 vs. 0.787 ± 0.025, p = 0.008; 12 weeks: 0.866 ± 0.024 vs. 0.835 ± 0.016, p = 0.023) and to SBBT at 4 and 8 weeks (p < 0.001 and p = 0.016, respectively). The TBT group demonstrated significantly lower HI and EFI compared to both SBBT and LBBT groups (p < 0.05), indicating faster healing and shorter treatment times. Although SBBT showed slightly higher PVR values than LBBT, the differences were not statistically significant.ConclusionTrifocal bone transport leads to faster bone regeneration and shorter treatment times compared to bifocal techniques, particularly for longer bone defects. The study demonstrates that defect length alone may not be the primary factor influencing regeneration rates in bifocal transport. PVR proves to be a reliable and cost-effective tool for assessing bone regeneration in different bone transport techniques, offering potential for guiding clinical decision-making. These findings suggest that trifocal transport should be considered as a preferred method for treating larger bone defects, especially when minimizing treatment time is crucial.

A recommended sampling strategy for genetic identification of Second World War victims in Slovenia

Skeletonized human remains from Second World War mass graves in Slovenia are a major challenge in genetic identification, and bones with a high DNA yield must be selected for successful identification. The goal of this study was to construct skeletal sampling strategy recommendations through comparison of the most appropriate groups of skeletal elements. Altogether, 566 bones and teeth from the same mass grave were compared, half analyzed in this study and half in previous studies performed by our group. After anthropological examination, mechanical and chemical cleaning was performed, followed by bone and tooth powdering. Total demineralization of 0.5 g of bone and tooth was followed by extraction and purification of DNA with a Biorobot EZ1 device (Qiagen). The qPCR PowerQuant kit (Promega) was used to measure the amount of DNA, and statistical analysis was performed. Skeletal elements were selected according to known better preservation of DNA in the human body, and they were arranged in seven groups: petrous bone, long bones (femur and tibia), torso bones (first rib and 12th vertebra), metacarpals, metatarsals, short and sesamoid bones (talus, navicular, medial cuneiform, cuboid, calcaneus, and patella), and teeth. Sampling strategy recommendations were constructed based on DNA quantity and quality results. The petrous bone group, metacarpal group, torso bone group, and short and sesamoid bone group produced the highest DNA yields. Accordingly, in addition to standard sampling of long bones (femurs and tibias) and teeth, those additional bone types should be collected for Slovenian Second World War victim identification.

Prenatal diagnosis of fetal skeletal anomalies via whole-exome sequencing in a tertiary referral center

The accurate prenatal diagnosis of skeletal anomaly (SKA) using prenatal imaging alone remains challenging. We aimed to investigate the efficacy of whole-exome sequencing (WES) in the prenatal molecular genetic diagnosis of skeletal system abnormalities, with or without additional ultrasound anomalies. All fetuses with SKA were subjected to sequential genetic tests, and after excluding fetal chromosomal abnormalities and clinically significant copy number variations (CNVs) consistent with the observed phenotype, the affected fetuses were further subjected to WES. The clinical features of fetal SKA were collected, and the results of molecular genetic testing and perinatal outcomes were analyzed. Following negative routine genetic test results of the 78 fetuses, trio-WES was conducted for 73 fetuses, and fetus-only WES (single WES) was performed for five fetuses due to parental refusal. Fetal skeletal system abnormalities in our cohort were subdivided into seven groups: 39 (50%) had short long bones, 14 (17.9%) had abnormal limb morphology, 4 (5.1%) had polydactyly, 4 (5.1%) had the absence of the radius tibia or tibiofibula, 5 (6.4%) had spine anomalies, 6 (7.7%) had strephenopodia, and 6 (7.7%) had multiple deformities. In total, we identified the molecular diagnoses for 32/78 fetuses with SKAs, and confirmed 41 pathogenic/likely pathogenic variants in 28 genes, including nine novel variants in our cohort. The overall diagnostic rate was 41% (32/78). Our findings demonstrate that WES can greatly improve the genetic diagnostic rate of fetal SKAs following routine genetic testing, which can comprehensively guide perinatal management and help assess the risk of recurrence in future pregnancies. Our data also provide a basis for the association between the SKA phenotype and related genotypes and expand the spectrum of fetal SKA phenotypes and related genes.

Ancient Species of the Genus <i>Dvinosaurus</i> (Temnospondyli, Dvinosauria) from the Permian Sundyr Tetrapod Assemblage of Eastern Europe

From the Sundyr-1 reference locality of the Sundyr faunal assemblage of Eastern Europe (Upper Permian, Upper Severodvinian Substage, Suchonica vladimiri Assemblage Zone), the oldest species of the genus Dvinosaurus Amalitzky, 1921 Dvinosaurus gubini sp. nov. The diagnostic criterions for the new species are its smaller size compared to other dvinosaurs, the narrowest skull, short and wide zygomatic bone, parasphenoid body with a more wide base of the cultriform process and a well ossified basisphenoid, a strongly curved dentary with a well-defined symphyseal crest extending downward from the labial side of the symphysis and, in a several cases, with a single symphyseal canine, a large angle (135–152°) between the clavicular plate and the dorsal process of the clavicle, narrow areas of the interclavicle for insertion of the clavicles, narrow entepicondylus of the humerus. The size, narrowness of the skull, the presence of a single symphyseal canine, and hypocentrum structure bring together a new form closer to the basal Dvinosauria, in particular, with ancestral Trimerorhachidae.

The transcription factor BBX regulates phosphate homeostasis through the modulation of FGF23

Fibroblast growth factor 23 (FGF23) plays an important role in phosphate homeostasis, and increased FGF23 levels result in hypophosphatemia; however, the molecular mechanism underlying increased FGF23 expression has not been fully elucidated. In this study, we found that mice lacking the bobby sox homolog (Bbx−/−) presented increased FGF23 expression and low phosphate levels in the serum and skeletal abnormalities such as a low bone mineral density (BMD) and bone volume (BV), as well as short and weak bones associated with low bone formation. Osteocyte-specific deletion of Bbx using Dmp-1-Cre resulted in similar skeletal abnormalities, elevated serum FGF23 levels, and reduced serum phosphate levels. In Bbx−/− mice, the expression of sodium phosphate cotransporter 2a (Npt2a) and Npt2c in the kidney and Npt2b in the small intestine, which are negatively regulated by FGF23, was downregulated, leading to phosphate excretion/wasting and malabsorption. An in vitro Fgf23 promoter analysis revealed that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced transactivation of the Fgf23 promoter was significantly inhibited by BBX overexpression, whereas it was increased following Bbx knockdown. Interestingly, 1,25(OH)2D3 induced an interaction of the 1,25(OH)2D3 receptor (VDR) with BBX and downregulated BBX protein levels. Cycloheximide (CHX) only partially downregulated BBX protein levels, indicating that 1,25(OH)2D3 regulates BBX protein stability. Furthermore, the ubiquitination of BBX followed by proteasomal degradation was required for the increase in Fgf23 expression induced by 1,25(OH)2D3. Collectively, our data demonstrate that BBX negatively regulates Fgf23 expression, and consequently, the ubiquitin-dependent proteasomal degradation of BBX is required for FGF23 expression, thereby regulating phosphate homeostasis and bone development in mice.

Familial osteochondrodysplastic and cardiomyopathic syndrome in Chianina cattle.

Skeletal dysplasia encompasses a heterogeneous group of genetic disorders characterized by an abnormal development of bones, joints, and cartilage. Two Chianina half-sibling calves from consanguineous mating with congenital skeletal malformations and cardiac abnormalities were identified. To characterize the disease phenotype, to evaluate its genetic cause, and to determine the prevalence of the deleterious alleles in the Chianina population. Two affected calves, their parents and 332 Chianina bulls. The affected animals underwent clinicopathological investigation. Whole-genome sequencing trio-approach and PCR-based assessment of the frequency of TDP-glucose 4,6-dehydratase (TGDS) and laminin subunit alpha 4 (LAMA4) alleles were performed. The cases presented with retarded growth, poor nutritional status associated with muscular atrophy and angular deformities of the hindlimbs. Radiologic examination identified generalized osteopenia and shortening of the limb long bones. Necropsy showed osteochondrodysplastic limbs and dilatation of the heart right ventricle. On histological examination, the physeal cartilages were characterized by multifocal mild to moderate loss of the normal columnar arrangement of chondrocytes. Osteopenia also was observed. Genetic analysis identified a missense variant in TGDS and a splice-site variant in LAMA4, both of which were homozygous in the 2 cases. Parents were heterozygous and allele frequency in the Chianina population for the TGDS variant was 5% and for the LAMA4 variant was 2%. Genetic findings identified 2 potentially pathogenic alleles in TGDS and LAMA4, but no clear mode of inheritance could be determined.

Identification of two novel genetic variants for Ellis-van Creveld syndrome from a Chinese family through whole exome sequencing

ObjectiveThis study conducted genetic testing and analysis on the fetal tissue of a terminated pregnancy to clarify the cause of the fetal abnormalities. MethodsA fetus with multiple malformations detected during mid-pregnancy was terminated. Trio whole exome sequencing (Trio-WES) was performed on the fetal tissue. The identified gene variants were verified from parents’ blood samples using Sanger sequencing. ResultsPrenatal ultrasound indicated that the fetus had an atrioventricular septal defect, thoracic narrowing, short and angulated long bones of the limbs, polydactyly of the hands, and right clubfoot. The high-throughput sequencing results showed that the fetus had a heterozygous splicing variant c.939+1G>A and a heterozygous frameshift deletion variant c.528delC (p. Ser177Alafs19) in the Ellis-van Creveld (EVC) gene. Sanger sequencing confirmed that the maternal variant c.939+1G>A and the paternal variant c.528delC (p. Ser177Alafs19) were the sources of the two EVC gene variants in the fetus. Combined with the genetic analysis and prenatal ultrasound findings, this family was diagnosed with Ellis-van Creveld syndrome. ConclusionTwo novel causative genetic variants for EVC syndrome were identified. The findings would expand the mutational spectrum of the EVC gene and demonstrate that whole-exome sequencing is a powerful tool for the clinical diagnosis of genetically heterogeneous diseases.

The primary stability of ultrashort residual proximal femur fixed with triangular fixation stem prosthesis: a comparative biomechanical study based on sawbones models.

Tumor resection near the proximal end of the femur and revision surgery of the distal femoral prosthesis may result in a very short bone segment remaining at the proximal end of the femur, known as ultrashort residual proximal femur (URPF). In this study, we propose a triangular fixation stem (TFS) prosthesis to improve the fixation of URPF. The aim of this research is to investigate the biomechanical properties of the TFS prosthesis and compare it with the conventional stem (CS) prosthesis through in vitro biomechanical experiments, providing preliminary biomechanical evidence for prosthetic fixation of URPF. A biomechanical study was conducted using Sawbones to explore initial stability. Twelve Sawbones were used to create a bone defect model, and prostheses were designed and fabricated to emulate TFS fixation and CS fixation structures. Axial compression and horizontal torsion experiments were performed on the fixed models using a mechanical testing machine, recording maximum displacement, maximum torque, and femoral strain conditions. Under an axial compressive load of 2800N, the overall displacement of the TFS group was 3.33 ± 0.58mm, which was significantly smaller than that of the CS group (4.03 ± 0.32mm, P = 0.029). The femoral samples of the TFS group demonstrated that the strain value alterations at the medial points 2, 3, 5, 6 and the lateral point 10 were conspicuously smaller than those of the conventional stem group (P < 0.05). Under torsional loads at levels of 1°, 3°, and 5°, the torques of the TFS group were 3.86 ± 0.69Nm, 3.90 ± 1.26Nm, and 4.39 ± 1.67Nm respectively, all of which were significantly greater than those of the CS group (1.82 ± 0.82Nm, P < 0.001; 2.05 ± 0.89Nm, P = 0.016; 1.96 ± 0.50Nm, P = 0.015 respectively). The TFS prosthesis improves fixation strength and reduces strain on the femur's proximal surface. Compared to CS fixation, it offers better resistance to compression and rotation, as well as improved initial stability.

Successful Anesthetic Management for Mandibular Neoplasm Resection in a Patient with Osteogenesis Imperfecta: A Case Report

Background: Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and deformities. Patients with mandibular neoplasms and suspected OI require careful anesthetic management to avoid complications. This case report describes the successful anesthetic management of a patient with a mandibular neoplasm and suspected OI. Case presentation: A 33-year-old man presented with a large mandibular tumor causing airway obstruction and difficulty eating. He had physical features suggestive of OI, including short stature, bone deformities, and abnormal tooth growth. Preoperative evaluation revealed a difficult airway due to the tumor and potential cervical spine instability. Anesthesia was induced with propofol and atracurium after securing the airway via ultrasound-guided tracheostomy under local anesthesia. The tumor was resected successfully, and the patient recovered without complications. Conclusion: Anesthetic management in patients with suspected OI and mandibular neoplasms requires careful planning and execution. A multidisciplinary approach, including preoperative evaluation, airway management strategies, and close postoperative monitoring, is crucial for successful outcomes.

Fetal Soft Marker in Obstetrics Ultrasound

Abstract Background Mid trimester scans in specific have become a standard part of antenatal care. Soft markers are reported to be present in approaching 11-14% of all second trimester ultrasound scanning Aim of the Work Detection of the soft markers and evaluating the benefit of each ultrasound soft marker and identify if there is a specific soft marker should be looked for standard on ultrasound scanning. Patients and Methods Routine 16-24 weeks of gestational scan had been performed at the outpatient clinic radiological department to detect all soft markers. Patients had been followed up and chromosomal karyotyping done for the new born to confirm the final diagnosis. Generally studied soft markers included fetal ventricomegaly, choroid plexus cysts, absent or hypo plastic nasal bone, thickened nuchal fold, intracardiac echogenic focus, short long bones, single umbilical artery, echogenic bowel and pyelectasis. Results As regards the validity of different soft markers in the detection of aneuploidy in this study we found that the existence of two soft markers or more had the highest sensitivity 66.7%, NVP 92.0%, inter cardiac echogenic foci had the highest specificity100 % &amp;= PPV 100%, NPV 87.2%, followed by large choroid plexus's cyst NVP 87.9%, Specificity 85.3%. Conclusion We establish a relation between ultrasonic soft markers and post natal aneuploidy. Maternal age ≥35.0 years had highest balanced characteristics of diagnosis, followed by having two or more signs &amp; positive history of consanguinity.

Lower extremity osseointegration — a review of the current experiences and expectations

Transcutaneous osseointegration for amputees (TOFA), an alternative approach to limb-loss rehabilitation, offers an enhanced quality of life and mobility, overcoming some challenges associated with amputation. This review presents evolution, surgical techniques, patient selection principles, and outcomes associated with TOFA. Notable points include the recognition that press-fit osseointegration techniques and implants achieve the quality of life and mobility improvements with a single surgical episode. Infection remains the most common adverse event, but uncommonly requires additional surgery, and rarely requires implant removal. Press-fit osseointegration has proven suitable for rehabilitating a broad range of patients with pelvic, transfemoral, or transtibial amputation performed to manage trauma, cancer, infection, chronic pain, and deformity. This technigue is safe for patients with vascular disease, diabetes mellitus, short residual bones, and osteoporotic residual bones. This article serves as a central resource for understanding the principles and techniques of osseointegration.

Bone-periosteal-muscle flap for ulnar lengthening in children with congenital radial club hand

Background. Congenital radial club hand is characterized by the underdevelopment of all forearm structures. Ulnar bone shortening ranges from 24.7% to 50.0% compared to the intact limb. The aim of the study was to evaluate the outcomes of ulnar lengthening by distraction osteogenesis in patients with congenital radial club hand type IV who underwent osteotomy with the formation of a bone-periosteal-muscle flap, and to compare these results with the treatment outcomes of the patients who had standard (oblique) ulnar osteotomy. Methods. The main group consisted of 20 patients who underwent osteotomy with the formation of a bone-periosteal-muscle flap during ulnar lengthening between 2019 and 2022. The control group included 19 patients (22 forearms) who underwent oblique ulnar osteotomy between 1998 and 2018. The following indicators were evaluated: length of the regenerate, distraction time, correction period, fixation index, osteosynthesis index, and complications. Results. A lengthening of 4.1 cm was achieved (30.7% of the initial ulnar bone length). The correction of angular deformity was 71.4%. Greater correction was achieved with osteotomy in the proximal ulna. In the subgroup with proximal segment osteotomy, the distraction and osteosynthesis indices were 25.6 and 25.7 days/cm, respectively. In the mid-third osteotomy group, these indices were 42.3 and 42.6 days/cm, respectively. Complications were limited to inflammatory phenomena in 30% of cases. All patients in the main group exhibited successful regenerate formation. Thus, the bone fragment with a periosteal-muscle pedicle serves as an additional source of osteogenesis during distraction. Conclusions. This study demonstrates the appropriateness of osteotomy with the formation of a bone-periosteal-muscle flap in children with congenital radial club hand. This technique allows for greater deformity correction, a shortened regenerate formation period, and a reduction in complications.