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Biological Reviews of the Cambridge... Apr 2024The question of what the ancient life cycle of tetrapods was like forms a key component in understanding the origin of land vertebrates. The existence of distinct larval...
The question of what the ancient life cycle of tetrapods was like forms a key component in understanding the origin of land vertebrates. The existence of distinct larval forms, as exemplified by many lissamphibians, and their transformation into adults is an important aspect in this field. The temnospondyls, the largest clade of Palaeozoic-Mesozoic non-amniote tetrapods, covered a wide ecomorphological range from fully aquatic to terrestrial taxa. In various species, rich ontogenetic data have accumulated over the past 130 years, permitting the study of early phases of temnospondyl development. In temnospondyls, eight ontogenetic phases have been identified in which the skeleton formed. In branchiosaurids and the eryopiform Sclerocephalus, large parts of the ossification sequence are now known. Most taxa in which small specimens are preserved had aquatic larvae with external gills that superficially resemble larval salamanders. In the edopoids, dvinosaurs, and eryopiforms, the larvae developed slowly, with incompletely ossified axial and appendicular skeletons, but possessed a fast-developing dermal skull with strong teeth. Irrespective of adult terrestriality or a fully aquatic life, there was no drastic transformation during later ontogeny, but a slow and steady acquisition of adult features. In dissorophoids, the limbs developed at a much faster pace, whereas skull formation was slowed down, especially in the amphibamiforms, and culminating in the neotenic Branchiosauridae. In the zatracheid Acanthostomatops, slow but profound transformation led to a fully terrestrial adult. The basal dissorophoid Stegops retained rapid development of dermal skull bones and established a fully dentigerous, strongly ossified palate early. In Micromelerpeton, formation of the last skull bones was slightly delayed and metamorphosis remained a long and steady phase of morphological transformations. In amphibamiforms, metamorphosis became more drastic, with an increasing number of events packed into a short phase of ontogeny. This is exemplified by Apateon, Platyrhinops, and Amphibamus in which this condensation was maximised. We distinguish three different types of metamorphosis (morphological, ecological and drastic) that evolved cumulatively in early tetrapods and within temnospondyls.
PubMed: 38599802
DOI: 10.1111/brv.13084 -
Journal of Bone and Mineral Research :... Apr 2024Achondroplasia, the most common form of disproportionate short stature, is caused by gain-of-function point mutations in fibroblast growth factor receptor 3 (FGFR3)....
Achondroplasia, the most common form of disproportionate short stature, is caused by gain-of-function point mutations in fibroblast growth factor receptor 3 (FGFR3). Abnormally elevated activation of FGFR3 modulates chondrocyte proliferation and differentiation via multiple signaling pathways, such as the MAPK pathway. Using a mouse model mimicking achondroplasia (Fgfr3Y367C/+), we have previously shown that daily treatment with infigratinib (BGJ398), a selective and orally bioavailable FGFR1-3 inhibitor, at a dose of 2 mg/kg, significantly increased bone growth. In this study, we investigated the activity of infigratinib administered at substantially lower doses (0.2 and 0.5 mg/kg, given once daily) and using an intermittent dosing regimen (1 mg/kg every 3 days). Following a 15-day treatment period, these low dosages were sufficient to observe significant improvement of clinical hallmarks of achondroplasia such as growth of the axial and appendicular skeleton and skull development. Immunohistological labeling demonstrated the positive impact of infigratinib on chondrocyte differentiation in the cartilage growth plate and the cartilage end plate of the vertebrae. Macroscopic and microcomputed analyses showed enlargement of the foramen magnum area at the skull base, thus improving foramen magnum stenosis, a well-recognized complication in achondroplasia. No changes in FGF23 or phosphorus levels were observed, indicating that the treatment did not modify phosphate homeostasis. This proof-of-concept study demonstrates that infigratinib administered at low doses has the potential to be a safe and effective therapeutic option for children with achondroplasia.
PubMed: 38590263
DOI: 10.1093/jbmr/zjae051 -
Journal of Orthopaedic Surgery and... Apr 2024The goal of this study is to propose a classification system with a common nomenclature for radiographic observations of periprosthetic bone changes following cTDR.
BACKGROUND
The goal of this study is to propose a classification system with a common nomenclature for radiographic observations of periprosthetic bone changes following cTDR.
METHODS
Aided by serial plain radiographs from recent cTDR cases (34 patients; 44 devices), a panel of experts assembled for the purpose of creating a classification system to aid in reproducibly and accurately identifying bony changes and assessing cTDR radiographic appearance. Subdividing the superior and inferior vertebral bodies into 3 equal sections, observed bone loss such as endplate rounding, cystic erosion adjacent to the endplate, and cystic erosion not adjacent to the endplate, is recorded. Determining if bone loss is progressive, based on serial radiographs, and estimating severity of bone loss (measured by the percentage of end plate involved) is recorded. Additional relevant bony changes and device observations include radiolucent lines, heterotopic ossification, vertebral body olisthesis, loss of core implant height, and presence of device migration, and subsidence.
RESULTS
Serial radiographs from 19 patients (25 devices) implanted with a variety of cTDR designs were assessed by 6 investigators including clinicians and scientists experienced in cTDR or appendicular skeleton joint replacement. The overall agreement of assessments ranged from 49.9% (95% bootstrap confidence interval 45.1-73.1%) to 94.7% (95% CI 86.9-100.0%). There was reasonable agreement on the presence or absence of bone loss or radiolucencies (range: 58.4% (95% CI 51.5-82.7%) to 94.7% (95% CI 86.9-100.0%), as well as in the progression of radiolucent lines (82.9% (95% CI 74.4-96.5%)).
CONCLUSIONS
The novel classification system proposed demonstrated good concordance among experienced investigators in this field and represents a useful advancement for improving reporting in cTDR studies.
Topics: Humans; Treatment Outcome; Diskectomy; Total Disc Replacement; Cervical Vertebrae; Neck; Intervertebral Disc Degeneration
PubMed: 38566203
DOI: 10.1186/s13018-024-04679-y -
Journal of Morphology Apr 2024The osteohistology of vertebrates provides a reliable source to deduce biological information, particularly regarding growth and development. Although osteohistological...
The osteohistology of vertebrates provides a reliable source to deduce biological information, particularly regarding growth and development. Although osteohistological studies in Neosuchia (Crocodyliformes, Mesoeucrocodylia) are relatively numerous, the number of species studied within the group is still small. Extant crocodilians are known to exhibit intraspecific variability linked to environmental conditions, habitat, feeding, and other intrapopulation factors. Here, we analyzed the osteohistology of the living South American Caiman latirostris throughout posthatching ontogeny. The histology of several appendicular bones of 13 different-sized captive and wild individuals were examined. Although some thin sections revealed the classic lamellar, parallel-fibered, or woven bone matrices, others showed a variation and a mix between the organization of the bone tissue. These histological differences are likely related to variability in the growth dynamics of caimans. In some bones of the juveniles studied, remnants of embryonic bone were observed. Osteohistological variation related to prevailing environmental conditions is documented. Furthermore, our results show ontogenetic variation in the type of bone tissues deposited throughout the development of C. latirostris. This study offers a broad framework for life history interpretations for C. latirostris and provides insight into the evolutionary history and ontogenetic growth of extinct crocodylian lineages.
Topics: Humans; Animals; Alligators and Crocodiles; Bone and Bones; Biological Evolution; Ecosystem; Growth and Development
PubMed: 38558429
DOI: 10.1002/jmor.21687 -
The American Journal of Case Reports Mar 2024BACKGROUND Erdheim-Chester disease (ECD) is a rare neoplasm of histiocytes that is characterized by prominent involvement of the long bones. Approximately 1500 cases...
BACKGROUND Erdheim-Chester disease (ECD) is a rare neoplasm of histiocytes that is characterized by prominent involvement of the long bones. Approximately 1500 cases have been reported since the disease was first described in 1930. The imaging appearance of ECD can be highly variable given the numerous systems it can affect. In this case report we discuss a patient whose ECD was occult on multiple imaging modalities. CASE REPORT We report the case of a 60-year-old woman who presented with sub-acute left knee and calf pain that led to an MRI. She was found to have innumerable marrow-replacing lesions in the axial and appendicular skeleton visualized on the initial MRI, as well as on an ¹⁸F-FDG PET/CT scan. The patient did not have extraosseous abnormal uptake on the PET/CT. Subsequently, a lesion from the left iliac bone was histologically confirmed as ECD on the basis of positive staining for CD68 and CD163 and negative staining for CD1a. Osseous lesions in ECD have a distinct imaging appearance and are typically detected by radiography and bone scintigraphy, among other modalities; however, the lesions in this case were unexpectedly absent from those studies. CONCLUSIONS If there is a high degree of suspicion for ECD, 18F-FDG PET/CT and/or MRI may be necessary for adequate visualization of bone lesions, given that those lesions can have an infiltrative nature that may be difficult to image with other anatomic imaging modalities. Use of 18F-FDG PET/CT and/or MRI may also lead to adequate guidance of confirmatory biopsy.
Topics: Female; Humans; Middle Aged; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Erdheim-Chester Disease; Magnetic Resonance Imaging; Tomography, X-Ray Computed
PubMed: 38553814
DOI: 10.12659/AJCR.941169 -
JBMR Plus Apr 2024Achondroplasia (ACH) is a skeletal dysplasia characterized by short-limbed short stature caused by the gain-of-function mutations in the fibroblast growth factor...
Achondroplasia (ACH) is a skeletal dysplasia characterized by short-limbed short stature caused by the gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Activated FGFR3, which is a negative regulator of bone elongation, impairs the growth of long bones and the spinal arch by inhibiting chondrocyte proliferation and differentiation. Most patients with ACH have spinal canal stenosis in addition to short stature. Meclozine has been found to inhibit FGFR3 via drug repurposing. A 10-d treatment with meclozine promoted long-bone growth in a mouse model of ACH ( mice). This study aimed to evaluate the effects of long-term meclozine administration on promoting bone growth and the spinal canal in mice. Meclozine (2 mg/kg/d) was orally administered to mice for 5 d per wk from the age of 7 d to 56 d. Meclozine (2 mg/kg/d) significantly reduced the rate of death or paralysis and improved the length of the body, cranium, and long bones in male and female mice. Micro-computed tomography analysis revealed that meclozine ameliorated kyphotic deformities and trabecular parameters, including BMD, bone volume/tissue volume, trabecular thickness, and trabecular number at distal femur of mice in both sexes. Histological analyses revealed that the hypertrophic zone in the growth plate was restored in mice following meclozine treatment, suggesting upregulation of endochondral ossification. Skeletal preparations demonstrated that meclozine restored the spinal canal diameter in mice in addition to improving the length of each bone. The 2 mg/kg/d dose of meclozine reduced the rate of spinal paralysis caused by spinal canal stenosis, maintained the growth plate structure, and recovered the bone quality and growth of axial and appendicular skeletons of mice in both sexes. Long-term meclozine administration has the potential to ameliorate spinal paralysis and bone growth in patients with ACH.
PubMed: 38544920
DOI: 10.1093/jbmrpl/ziae018 -
Journal of Human Evolution Apr 2024Biased skeletal part representation is a key element for making inferences about transport decisions, carcass procurement, and use patterns in anthropogenic...
Biased skeletal part representation is a key element for making inferences about transport decisions, carcass procurement, and use patterns in anthropogenic accumulations. In the absence of destructive taphonomic processes, it is often assumed that the abundance of different anatomical portions represents selective transport and discard patterns of human groups. Because body parts may be transported for specific products such as meat, marrow or grease, a pattern that usually attracts attention in many archaeological sites is the low proportions of appendicular epiphyses. Here we present the case of faunal assemblages from the lower stratigraphic sequence of Qesem Cave, Israel, dated to ca. 430 to 300 ka. All bone accumulations are characterized by a biased skeletal profile including mainly long-limb bones and a virtual absence of epiphyses. The assemblages also show density-mediated attrition not linked to fossil-diagenetic processes, a targeted specific destruction to the most greasy articular ends and an almost total absence of carnivore intervention. Our goal here is to explore the processes that entail the destruction of appendicular epiphyses at Qesem Cave, as well as propose viable hypotheses to explain their underrepresentation on-site. Our results shed light on the domestic activities linked to the processing of bones at the site and support the importance of animal grease in the caloric intake of Middle Pleistocene humans.
Topics: Animals; Humans; Israel; Hominidae; Bone and Bones; Fossils; Caves; Archaeology
PubMed: 38518437
DOI: 10.1016/j.jhevol.2024.103509 -
Journal of Orthopaedic Trauma Jun 2024To determine if a multidisciplinary institutional protocol can optimize the time to antibiotic (Abx) administration for open fractures (openFx) and improve compliance...
OBJECTIVES
To determine if a multidisciplinary institutional protocol can optimize the time to antibiotic (Abx) administration for open fractures (openFx) and improve compliance with the administration of Abx prophylaxis during trauma activation.
DESIGN
Retrospective pre-post study design.
SETTING
Single Level II Trauma Center.
PATIENT SELECTION CRITERIA
All patients who triggered a trauma activation with suspected openFx and were treated according to the institutional single antibiotic regimen were eligible for inclusion. Patients were excluded if fractures did not involve the appendicular skeleton. Patients treated before implementation of a standardized institutional protocol where premixed IV bags of antibiotics were stocked in automated dispensing systems within ED trauma bays (January 2021-October 2022) were defined as the "pre" group and those treated following implementation the "post" group.
OUTCOME MEASURES AND COMPARISONS
The primary outcome was time from trauma bay arrival to antibiotic aministration, measured in minutes, with comparisons made between preprotocol and postprotocol implementation. Secondary outcomes for comparison included rates (%) of time to Abx <60 minutes, allergic reactions, acute kidney injury, ototoxicity, surgical site infection, multi-drug-resistant organisms identified in blood or biopsy cultures in cases requiring reoperation, and Clostridium difficile infection in the gastrointestinal system, confirmed by stool test results, within 30 days.
RESULTS
Twenty-four patients (mean age 39.5 ± 16.3 years) met the criteria after protocol implementation compared with 72 patients (mean age 34.3 ± 14.8 years) before implementation. Implementation of the institutional protocol resulted in a significant reduction in the time to Abx administration for openFx from 87.9 ± 104.6 minutes to 22.2 ± 12.8 minutes in the postprotocol group ( P < 0.001). In addition, only 53% in the preprotocol group received Abx within 60 minutes compared with 96% in postprotocol group ( P < 0.001). Post hoc power analysis revealed that the study was powered at 92% (effect size = 0.72) to detect a significant difference between the preprotocol and postprotocol groups.
CONCLUSION
This study provides evidence that a multidisciplinary institutional protocol for the administration of Abx prophylaxis can be an effective strategy for optimizing the time to Abx administration in cases of suspected openFx. This protocol may be implemented in other trauma centers to optimize time to Abx administration for openFx.
LEVEL OF EVIDENCE
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Topics: Humans; Fractures, Open; Retrospective Studies; Antibiotic Prophylaxis; Female; Male; Anti-Bacterial Agents; Trauma Centers; Adult; Middle Aged; Clinical Protocols; Guideline Adherence; Surgical Wound Infection; Time-to-Treatment
PubMed: 38478500
DOI: 10.1097/BOT.0000000000002805 -
Bone & Joint Open Mar 2024The aim of this study is to determine the predictors of overall survival (OS) and predictive factors of poor prognosis of conventional high-grade osteosarcoma of the...
AIMS
The aim of this study is to determine the predictors of overall survival (OS) and predictive factors of poor prognosis of conventional high-grade osteosarcoma of the limbs in a single-centre in South Africa.
METHODS
We performed a retrospective cross-sectional analysis to identify the prognostic factors that predict the OS of patients with histologically confirmed high-grade conventional osteosarcoma of the limbs over ten years. We employed the Cox proportional regression model and the Kaplan-Meier method for statistical analysis.
RESULTS
This study comprised 77 patients at a three-year minimum follow-up. The predictors of poor OS were: the median age of ≤ 19 years (hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.92 to 0.99; p = 0.021); median duration of symptoms ≥ five months (HR 0.91; 95% CI 0.83 to 0.99; p < 0.037); metastasis at diagnosis (i.e. Enneking stage III) (HR 3.33; 95% CI 1.81 to 6.00; p < 0.001); increased alkaline phosphatase (HR 3.28; 95% CI 1.33 to 8.11; p < 0.010); palliative treatment (HR 7.27; 95% CI 2.69 to 19.70); p < 0.001); and amputation (HR 3.71; 95% CI 1.12 to 12.25; p < 0.032). In contrast, definitive surgery (HR 0.11; 95% CI 0.03 to 0.38; p < 0.001) and curative treatment (HR 0.18; 95% CI 0.10 to 0.33; p < 0.001) were a protective factor. The Kaplan-Meier median survival time was 24 months, with OS of 57.1% at the three years. The projected five-year event-free survival was 10.3% and OS of 29.8% (HR 0.76; 95% CI 0.52 to 1.12; p = 0.128).
CONCLUSION
In this series of high-grade conventional osteosarcoma of the appendicular skeleton from South Africa, 58.4% (n = 45) had detectable metastases at presentation; hence, an impoverished OS of five years was 29.8%. Large-scale future research is needed to validate our results.
PubMed: 38471520
DOI: 10.1302/2633-1462.53.BJO-2023-0159.R1 -
Academic Radiology Mar 2024Aiming to offset image quality limitations in radiographs due to superimposition, this study investigates the diagnostic potential of appendicular skeleton tomosynthesis.
RATIONALE AND OBJECTIVES
Aiming to offset image quality limitations in radiographs due to superimposition, this study investigates the diagnostic potential of appendicular skeleton tomosynthesis.
MATERIALS AND METHODS
Eight cadaveric extremities (four hands and feet) were examined employing the prototypical tomosynthesis mode of a twin robotic X-ray scanner. 12 protocols with varying sweep angles (10, 20 vs. 40°), frame rates (13 vs. 26 fps), and tube voltages (60 vs. 80 kV) were compared to radiographs. Four radiologists separately evaluated cortical and trabecular bone visualization and fracture patterns. Interreader reliability was assessed based on the intraclass correlation coefficient (ICC).
RESULTS
Radiation dose in radiography was 0.59 ± 0.20 dGy * cm versus 0.11 ± 0.00 to 2.46 ± 0.17 dGy * cm for tomosynthesis. Cortical bone display was inferior for radiographs compared to 40° and 20° tomosynthesis. Best results were ascertained for the 80 kV/40°/26 fps protocol. Trabecular bone depiction was also superior in tomosynthesis (p ≤ 0.009) and best with the 80 kV/10°/26 fps setting. Interreader reliability was moderate for cortical bone display (ICC 0.521, 95% confidence interval 0.356-0.641) and good for trabecular bone (0.759, 0.697-0.810). Diagnostic accuracy for articular involvement and multifragment situations was higher in tomosynthesis (93.8-100%/92.2-100%) vs. radiography (85.9%/82.8%.). Diagnostic confidence was also better in tomosynthesis (p ≤ 0.003).
CONCLUSION
Compared to radiography, tomosynthesis allows for superior assessability of cortical and trabecular bone and fracture morphology, especially at high framerates. Operating on a multipurpose X-ray system, tomosynthesis of the appendicular skeleton can be performed without additional scanner hardware.
PubMed: 38448327
DOI: 10.1016/j.acra.2024.02.020