RESUMO
Neuroanatomists have long speculated that expanded primate brains contain an increased morphological diversity of inhibitory neurons (INs)1, and recent studies have identified primate-specific neuronal populations at the molecular level2. However, we know little about the developmental mechanisms that specify evolutionarily novel cell types in the brain. Here, we reconstruct gene expression trajectories specifying INs generated throughout the neurogenic period in macaques and mice by analysing the transcriptomes of 250,181 cells. We find that the initial classes of INs generated prenatally are largely conserved among mammals. Nonetheless, we identify two contrasting developmental mechanisms for specifying evolutionarily novel cell types during prenatal development. First, we show that recently identified primate-specific TAC3 striatal INs are specified by a unique transcriptional programme in progenitors followed by induction of a distinct suite of neuropeptides and neurotransmitter receptors in new-born neurons. Second, we find that multiple classes of transcriptionally conserved olfactory bulb (OB)-bound precursors are redirected to expanded primate white matter and striatum. These classes include a novel peristriatal class of striatum laureatum neurons that resemble dopaminergic periglomerular cells of the OB. We propose an evolutionary model in which conserved initial classes of neurons supplying the smaller primate OB are reused in the enlarged striatum and cortex. Together, our results provide a unified developmental taxonomy of initial classes of mammalian INs and reveal multiple developmental mechanisms for neural cell type evolution.
Assuntos
Evolução Biológica , Corpo Estriado , Desenvolvimento Embrionário , Macaca , Neurogênese , Neurônios , Bulbo Olfatório , Animais , Corpo Estriado/crescimento & desenvolvimento , Neurônios Dopaminérgicos , Feminino , Macaca/crescimento & desenvolvimento , Mamíferos , Camundongos , Neurogênese/fisiologia , Bulbo Olfatório/fisiologia , Gravidez , PrimatasRESUMO
An equitable approach by the American College of Medical Genetics and Genomics (ACMG) has recently recommended carrier screening for genes associated with moderate to severe autosomal recessive conditions with a carrier frequency of ≥1/200 in the Genome Aggregation Database exomes (gnomADv2.0.2). We analyzed carrier frequencies in gnomADv3.1.1 genomes representing diverse populations. ClinVar data on 35 996 pathogenic/likely pathogenic variants in 419 genes were used to estimate the gnomAD frequency of heterozygous carriers. We found that ninety-two genes had a carrier frequency of ≥1/200, of which 63 were shared between v3.1.1 and v2.0.2 and 29 were new in v3.1.1. Addition of new populations (Amish, Finnish and Middle Eastern) increased the number of new genes with a carrier frequency of ≥1/200 to 71. Changes in carrier frequencies were attributed to new gnomAD populations, different sample sizes, new ClinVar data, and technical differences between exomes and genomes. This study highlights the dynamic changes in carrier frequencies due to new datasets from diverse populations and provides updated carrier frequencies based on the combined data from 184 352 genomes and exomes in gnomAD. We recommend a periodic review for inclusion of new population data to update carrier screening panels in the future.
Assuntos
Exoma , Variação Genética , Genes Recessivos , Genômica , Heterozigoto , HumanosRESUMO
Peptide couplers (also known as amide bond-forming reagents or coupling reagents) are broadly used in organic chemical syntheses, especially in the pharmaceutical industry. Yet, occupational health hazards associated with this chemical class are largely unexplored, which is disconcerting given the intrinsic reactivity of these compounds. Several case studies involving occupational exposures reported adverse respiratory and dermal health effects, providing initial evidence of chemical sensitization. To address the paucity of toxicological data, a pharmaceutical cross-industry task force was formed to evaluate and assess the potential of these compounds to cause eye and dermal irritation as well as corrosivity and dermal sensitization. The goal of our work was to inform health and safety professionals as well as pharmaceutical and organic chemists of the occupational health hazards associated with this chemical class. To that end, 25 of the most commonly used peptide couplers and five hydrolysis products were selected for in vivo, in vitro, and in silico testing. Our findings confirmed that dermal sensitization is a concern for this chemical class with 21/25 peptide couplers testing positive for dermal sensitization and 15 of these being strong/extreme sensitizers. We also found that dermal corrosion and irritation (8/25) as well as eye irritation (9/25) were health hazards associated with peptide couplers and their hydrolysis products (4/5 were dermal irritants or corrosive and 4/5 were eye irritants). Resulting outcomes were synthesized to inform decision making in peptide coupler selection and enable data-driven hazard communication to workers. The latter includes harmonized hazard classifications, appropriate handling recommendations, and accurate safety data sheets, which support the industrial hygiene hierarchy of control strategies and risk assessment. Our study demonstrates the merits of an integrated, in vivo -in silico analysis, applied here to the skin sensitization endpoint using the Computer-Aided Discovery and REdesign (CADRE) and Derek Nexus programs. We show that experimental data can improve predictive models by filling existing data gaps while, concurrently, providing computational insights into key initiating events and elucidating the chemical structural features contributing to adverse health effects. This interactive, interdisciplinary approach is consistent with Green Chemistry principles that seek to improve the selection and design of less hazardous reagents in industrial processes and applications.
Assuntos
Irritantes , Saúde Ocupacional , Humanos , Peptídeos/farmacologia , Preparações Farmacêuticas , PeleRESUMO
Human pluripotent stem cells hold significant promise for regenerative medicine. However, long differentiation protocols and immature characteristics of stem cell-derived cell types remain challenges to the development of many therapeutic applications. In contrast to the slow differentiation of human stem cells in vitro that mirrors a nine-month gestation period, mouse stem cells develop according to a much faster three-week gestation timeline. Here, we tested if co-differentiation with mouse pluripotent stem cells could accelerate the differentiation speed of human embryonic stem cells. Following a six-week RNA-sequencing time course of neural differentiation, we identified 929 human genes that were upregulated earlier and 535 genes that exhibited earlier peaked expression profiles in chimeric cell cultures than in human cell cultures alone. Genes with accelerated upregulation were significantly enriched in Gene Ontology terms associated with neurogenesis, neuron differentiation and maturation, and synapse signaling. Moreover, chimeric mixed samples correlated with in utero human embryonic samples earlier than human cells alone, and acceleration was dose-dependent on human-mouse co-culture ratios. The altered gene expression patterns and developmental rates described in this report have implications for accelerating human stem cell differentiation and the use of interspecies chimeric embryos in developing human organs for transplantation.
Assuntos
Quimerismo , Células-Tronco Embrionárias Humanas , Neurogênese , Células-Tronco Pluripotentes , Animais , Células Cultivadas , Biologia Computacional , Células-Tronco Embrionárias Humanas/citologia , Células-Tronco Embrionárias Humanas/fisiologia , Humanos , Camundongos , Neurogênese/genética , Neurogênese/fisiologia , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/fisiologia , Especificidade da Espécie , Transcriptoma/genéticaRESUMO
BACKGROUND: Pediatric sports medicine is a new and rapidly growing subspecialty within orthopaedic surgery. However, there is very limited literature on the practice of pediatric sports medicine in North America. Therefore, the purpose of this study was to evaluate and describe the current practice patterns of orthopaedic surgeons specializing in pediatric sports medicine. METHODS: An online survey was distributed to orthopaedic surgeons specializing in pediatric sports medicine through the Pediatric Research in Sports Medicine Society. The purpose of the survey was to characterize (1) surgeon demographics, (2) the breakdown of different joint specialization, and (3) the specific procedures for joints that the surgeons specialize in. RESULTS: Responses from 55 orthopaedic surgeons were collected and analyzed. Most respondents considered pediatric sports medicine as the primary focus of their practice (89.1%, n=49/55). The number of fellowships completed was almost evenly split between either a single fellowship (52.7%, n=29/55) or 2 or more (47.3%, n=26/55). The most common combination of fellowships was pediatric orthopaedics and adult sports medicine (32.7%, n=18/55). Most survey respondents had been in practice for <10 years (69.0%, n=38/55) and were affiliated with an academic center (61.8%, n=34/55). On average, 77.5% of the patients treated were <18 years old. The knee joint was the most specialized joint, with 98.2% (n=54/55) respondents reporting that the knee joint constituted ≥25% of their practice. The knee joint constituted a mean of 52.1% of the respondents' overall practice, followed by the shoulder (15.2%), hip (13.9%), ankle (7.5%), elbow (7.1%), and wrist (4.2%). CONCLUSIONS: Pediatric sports medicine practices are variable and have distinct practice patterns in pediatric, orthopaedic, and adult sports practices. In the current study, most surgeons are less than 10 years into practice, affiliated with academic centers, and have typically completed either 1 or 2 fellowships after residency. Surgeons were most commonly specialized in the knee joint and cared for patients <18 years old. LEVEL OF EVIDENCE: Level of evidence IV.
Assuntos
Procedimentos Ortopédicos , Cirurgiões Ortopédicos , Ortopedia , Medicina Esportiva , Adolescente , Criança , Bolsas de Estudo , Humanos , Procedimentos Ortopédicos/métodosRESUMO
BACKGROUND: Understanding differences between types of study design (SD) and level of evidence (LOE) are important when selecting research for presentation or publication and determining its potential clinical impact. The purpose of this study was to evaluate interobserver and intraobserver reliability when assigning LOE and SD as well as quantify the impact of a commonly used reference aid on these assessments. METHODS: Thirty-six accepted abstracts from the Pediatric Orthopaedic Society of North America (POSNA) 2021 annual meeting were selected for this study. Thirteen reviewers from the POSNA Evidence-Based Practice Committee were asked to determine LOE and SD for each abstract, first without any assistance or resources. Four weeks later, abstracts were reviewed again with the guidance of the Journal of Bone and Joint Surgery (JBJS) LOE chart, which is adapted from the Oxford Centre for Evidence-Based Medicine. Interobserver and intraobserver reliability were calculated using Fleiss' kappa statistic (k). χ2 analysis was used to compare the rate of SD-LOE mismatch between the first and second round of reviews. RESULTS: Interobserver reliability for LOE improved slightly from fair (k=0.28) to moderate (k=0.43) with use of the JBJS chart. There was better agreement with increasing LOE, with the most frequent disagreement between levels 3 and 4. Interobserver reliability for SD was fair for both rounds 1 (k=0.29) and 2 (k=0.37). Similar to LOE, there was better agreement with stronger SD. Intraobserver reliability was widely variable for both LOE and SD (k=0.10 to 0.92 for both). When matching a selected SD to its associated LOE, the overall rate of correct concordance was 82% in round 1 and 92% in round 2 (P<0.001). CONCLUSION: Interobserver reliability for LOE and SD was fair to moderate at best, even among experienced reviewers. Use of the JBJS/Oxford chart mildly improved agreement on LOE and resulted in less SD-LOE mismatch, but did not affect agreement on SD. LEVEL OF EVIDENCE: Level II.
Assuntos
Ortopedia , Projetos de Pesquisa , Criança , Medicina Baseada em Evidências , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Competency-based education (CBE) seeks to determine resident proficiency in the knowledge, skills, and behaviors required for independent patient care. Multiple assessment instruments evaluate technical skills or direct patient care in the clinic setting, but there are few reports incorporating both within an orthopedic specialty rotation. This study reports a residency program's comprehensive CBE initiative using formative assessments in the clinic and operating room during a sports medicine rotation. MATERIALS AND METHODS: The sports medicine rotation used validated formative assessments to evaluate resident performance during clinic encounters and program-defined surgical entrustable professional activities (EPAs). Junior resident (postgraduate year [PGY] 1-2) EPAs included basic knee/shoulder arthroscopic procedures. Senior resident (PYG 5) EPAs comprised anterior cruciate ligament reconstruction, biceps tenodesis, shoulder stabilization, and rotator cuff repair. Assessment scores were compared between individuals and PGY groups. RESULTS: Sixty-six clinical skills (CS) and 106 surgical skills assessments were conducted for 22 residents in one academic year. Surgical skills assessments demonstrated significant differences between each PGY group (P < 0.01). All PGY2 and PGY5 residents achieved independence on the evaluated EPAs. PGY5s earned higher scores in CS assessments than the other classes (P < 0.01). PGY2 residents scored higher than PGY1s in 7 of 9 CS domains. CS independence was achieved by 21 of 22 residents by the end of the rotation. CONCLUSIONS: The CBE program effectively quantified expected differences in resident performance by PGY for clinic and surgical assessments on a sports medicine rotation. Assessments built an environment where feedback was more structured and standardized, creating a culture to improve resident education.
Assuntos
Artroscopia/educação , Competência Clínica/estatística & dados numéricos , Educação Baseada em Competências/métodos , Internato e Residência/métodos , Medicina Esportiva/educação , Educação Baseada em Competências/estatística & dados numéricos , Currículo , Humanos , Internato e Residência/estatística & dados numéricos , Avaliação de Programas e Projetos de SaúdeRESUMO
This study assesses whether currently available acute oral toxicity (AOT) in silico models, provided by the widely employed Leadscope software, are fit-for-purpose for categorization and labelling of chemicals. As part of this study, a large data set of proprietary and marketed compounds from multiple companies (pharmaceutical, plant protection products, and other chemical industries) was assembled to assess the models' performance. The absolute percentage of correct or more conservative predictions, based on a comparison of experimental and predicted GHS categories, was approximately 95%, after excluding a small percentage of inconclusive (indeterminate or out of domain) predictions. Since the frequency distribution across the experimental categories is skewed towards low toxicity chemicals, a balanced assessment was also performed. Across all compounds which could be assigned to a well-defined experimental category, the average percentage of correct or more conservative predictions was around 80%. These results indicate the potential for reliable and broad application of these models across different industrial sectors. This manuscript describes the evaluation of these models, highlights the importance of an expert review, and provides guidance on the use of AOT models to fulfill testing requirements, GHS classification/labelling, and transportation needs.
Assuntos
Simulação por Computador , Citotoxinas/toxicidade , Colaboração Intersetorial , Rotulagem de Produtos/classificação , Rotulagem de Produtos/normas , Relação Quantitativa Estrutura-Atividade , Administração Oral , Alternativas aos Testes com Animais/classificação , Alternativas aos Testes com Animais/métodos , Alternativas aos Testes com Animais/normas , Animais , Indústria Química/classificação , Indústria Química/normas , Simulação por Computador/tendências , Citotoxinas/administração & dosagem , Citotoxinas/química , Bases de Dados Factuais , Indústria Farmacêutica/classificação , Indústria Farmacêutica/normas , HumanosRESUMO
Pluripotent stem cells retain the developmental timing of their species of origin in vitro, an observation that suggests the existence of a cell-intrinsic developmental clock, yet the nature and machinery of the clock remain a mystery. We hypothesize that one possible component may lie in species-specific differences in the kinetics of transcriptional responses to differentiation signals. Using a liquid-handling robot, mouse and human pluripotent stem cells were exposed to identical neural differentiation conditions and sampled for RNA-sequencing at high frequency, every 4 or 10 minutes, for the first 10 hours of differentiation to test for differences in transcriptomic response rates. The majority of initial transcriptional responses occurred within a rapid window in the first minutes of differentiation for both human and mouse stem cells. Despite similarly early onsets of gene expression changes, we observed shortened and condensed gene expression patterns in mouse pluripotent stem cells compared to protracted trends in human pluripotent stem cells. Moreover, the speed at which individual genes were upregulated, as measured by the slopes of gene expression changes over time, was significantly faster in mouse compared to human cells. These results suggest that downstream transcriptomic response kinetics to signaling cues are faster in mouse versus human cells, and may offer a partial account for the vast differences in developmental rates across species.
Assuntos
Diferenciação Celular/genética , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , RNA-Seq/estatística & dados numéricos , Animais , Linhagem Celular , Biologia Computacional , Regulação da Expressão Gênica no Desenvolvimento , Células-Tronco Embrionárias Humanas/citologia , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Cinética , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Medicina Regenerativa , Especificidade da EspécieRESUMO
How species-specific developmental timing is controlled is largely unknown. By following human embryonic stem (ES) cell and mouse epiblast stem (EpiS) cell differentiation through detailed RNA-sequencing time courses, here we show that pluripotent stem cells closely retain in vivo species-specific developmental timing in vitro. In identical neural differentiation conditions in vitro, gene expression profiles are accelerated in mouse EpiS cells compared to human ES cells with relative rates of differentiation closely reflecting the rates of progression through the Carnegie stages in utero. Dynamic Time Warping analysis identified 3389 genes that were regulated more quickly in mouse EpiS cells and identified none that were regulated more quickly in human ES cells. Interestingly, we also find that human ES cells differentiated in teratomas maintain the same rate of differentiation observed in vitro in spite of being grown in a mouse host. These results suggest the existence of a cell autonomous, species-specific developmental clock that pluripotent stem cells maintain even out of context of an intact embryo.
Assuntos
Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Animais , Diferenciação Celular/genética , Linhagem Celular , Células-Tronco Embrionárias/citologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Camundongos SCID , Neurônios/citologia , Especificidade da Espécie , Teratoma/patologia , Fatores de TempoRESUMO
BACKGROUND: Anterior cruciate ligament (ACL) tears in children and adolescent patients are being diagnosed and treated at an ever-increasing rates. We performed a review of recent literature regarding care of children and adolescent athletes with an ACL injury. METHODS: PubMed database was searched for all papers related to treatment of children and adolescents with ACL injuries from October 1, 2012 to September 30, 2015, yielding 114 publications. RESULTS: A total of 59 papers were found to have contributed important new findings. Papers were selected based on new findings in the following categories: epidemiology, anatomy, risk factors, sex disparity, prevention, surgical outcomes, timing and associated pathologies, and rehabilitation and return to sport. CONCLUSIONS: Pediatric ACL injuries continue to rise and there are multiple surgical procedures that restore clinical function with good outcomes. Early surgical treatment is favored to prevent concomitant articular injuries. Early return to play can increase risk of reinjury and should be met with caution in this age group. Prevention strategies should be further studied and implemented in hopes of decreasing the incidence of this injury and the long-term potential damage. LEVEL OF EVIDENCE: Level 4-titerature review.
Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior , Traumatismos em Atletas/cirurgia , Adolescente , Lesões do Ligamento Cruzado Anterior/epidemiologia , Lesões do Ligamento Cruzado Anterior/patologia , Lesões do Ligamento Cruzado Anterior/prevenção & controle , Traumatismos em Atletas/epidemiologia , Traumatismos em Atletas/patologia , Traumatismos em Atletas/prevenção & controle , Criança , Humanos , Incidência , Volta ao Esporte , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: Developmental dysplasia of the hip (DDH), which encompasses a wide spectrum of disease from mild dysplasia to frank dislocation, is one of the most common developmental deformities of the lower extremities and one of the leading causes of future osteoarthritis and hip arthroplasty. Legg-Calvé-Perthes disease (LCPD) results from a vascular insult to the growing femoral epiphysis, which in turn can create permanent morphologic changes to the hip joint. Slipped capital femoral epiphysis (SCFE) occurs when the proximal femoral physis fails allowing the epiphysis to displace in relation to the metaphysis. Infections about the hip also create significant morbidity in the pediatric hip. METHODS: We searched the PubMed database for all studies related to DDH, LCPD, SCFE, and pediatric hip infections that were published between July 1, 2014 and August 31, 2017. The search was limited to English articles and yielded 839 papers. This project was initiated by the Pediatric Orthopaedic Society of North America Publications Committee and was reviewed and approved by the Pediatric Orthopaedic Society of North America Presidential Line. RESULTS: A total of 40 papers were selected for review based upon new and significant findings. Select historical manuscripts are also included to provide sufficient background information. CONCLUSIONS: DDH, LCPD, SCFE, and infections about the hip continue to be important topics in pediatric orthopaedics and areas of vital research. This manuscript reviews the most important recent literature on the diagnosis and treatment of these pediatric hip conditions. LEVEL OF EVIDENCE: Level V.
Assuntos
Artrite Infecciosa/cirurgia , Luxação Congênita de Quadril/cirurgia , Doença de Legg-Calve-Perthes/cirurgia , Escorregamento das Epífises Proximais do Fêmur/cirurgia , Artrite Infecciosa/microbiologia , Drenagem , Fêmur , Luxação Congênita de Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Humanos , Doença de Legg-Calve-Perthes/diagnóstico por imagem , América do Norte , Procedimentos Ortopédicos , Ortopedia , Osteoartrite , Escorregamento das Epífises Proximais do Fêmur/diagnóstico por imagem , Sociedades MédicasRESUMO
BACKGROUND: Multiple casting indices have been described to evaluate the adequacy of cast placement in pediatric distal forearm fractures. The aim of this study was to determine the intrarater and interrater reliability of the measurements of 5 common casting indices among members of an orthopaedic surgery residency program. The cast index, 3-point index, gap index, padding index, and Canterbury index were evaluated. METHODS: This was a single-center prospective cohort reliability study that included 12 members of an orthopaedic surgery residency. Participants were placed into 1 of 4 groups by level of training: physician assistants, junior residents, senior residents, and attending orthopaedic surgeons. Twelve radiographs of casted pediatric distal forearm fractures were measured by each participant on 2 separate occasions. Statistical analysis using the intraclass correlation coefficient was used to determine the intrarater and interrater reliability. RESULTS: The cast index was the only casting index to meet our criteria for good intrarater and interrater reliability. CONCLUSION: Continued use of the cast index as a tool to assess pediatric distal forearm cast application is supported by this study. LEVEL OF EVIDENCE: Level 2.
Assuntos
Moldes Cirúrgicos , Traumatismos do Antebraço/terapia , Fraturas Ósseas/terapia , Internato e Residência , Ortopedia/educação , Criança , Feminino , Traumatismos do Antebraço/diagnóstico por imagem , Fraturas Ósseas/diagnóstico por imagem , Humanos , Masculino , Variações Dependentes do Observador , Estudos Prospectivos , Radiografia , Reprodutibilidade dos TestesRESUMO
BACKGROUND: In a prior biomechanical study, 2-screw fixation of anatomically reduced slipped capital femoral epiphysis (SCFE) demonstrated marginally greater stability than single-screw fixation. However, the authors judged the benefits of a second screw to be minimal compared with the additional complication risk. A similar evaluation of fixation stability in unstable moderately displaced SCFE is performed. METHODS: SCFE model: Transverse periosteal incision and epiphyseal separation from the metaphysis by leveraging in 25-month-old porcine femurs. Four groups were evaluated: pinned (3.5 mm cortex screws; Synthes, Monument, CO) with no displacement (1 screw=group N1; 2 screws=group N2) or with moderate posterior-inferior displacement of 50% of the epiphyseal diameter (1 screw=group D1; 2 screws=group D2). Biomechanical testing: Cyclical shear forces (40 to 200 N, 1 Hz) were applied along the physeal plane. Maximum load increased by 100 N every 500 cycles until failure (epiphyseal translation greater than one third the epiphyseal diameter). Force cycles (the sum of the maximum cycle loads) and number of cycles to failure were reported. RESULTS: A sample from each D1 and D2 had fixation problems (D1, D2: n=4; N1, N2: n=5). One D1 failed through the femoral neck; all others failed through the epiphysis. The data showed nonsignificant trends of greater force cycles for nondisplaced over displaced (P=0.13) and for 2 screws over 1 (P=0.19). Number of cycles to failure showed similar trends, with no significant differences between nondisplaced and displaced (P=0.10) and screw number (P=0.13). Force cycles were significantly greater in the N2 group than in the D1 group. CONCLUSIONS: A trend toward higher force cycles to failure in nondisplaced and 2-screw groups was observed. Higher force cycles correspond to greater physeal stability and thus decreased risk for subsequent displacement. Within displacement groups, adding a second screw did not significantly increase stability. Reduction of displaced SCFE also did not significantly increase stability. Only the D1 and N2 groups were significantly different. CLINICAL RELEVANCE: Nondisplaced SCFE does not require 2 screws. In situ fixation of displaced SCFE might be optimized with 2 screws.
Assuntos
Parafusos Ósseos , Teste de Materiais/métodos , Procedimentos Ortopédicos , Complicações Pós-Operatórias/prevenção & controle , Escorregamento das Epífises Proximais do Fêmur , Animais , Fenômenos Biomecânicos , Parafusos Ósseos/efeitos adversos , Parafusos Ósseos/normas , Fêmur/diagnóstico por imagem , Fêmur/patologia , Fêmur/cirurgia , Humanos , Modelos Anatômicos , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/métodos , Radiografia , Escorregamento das Epífises Proximais do Fêmur/diagnóstico por imagem , Escorregamento das Epífises Proximais do Fêmur/cirurgia , SuínosRESUMO
BACKGROUND: We encountered multiple cases in which the US appearance of ruptured appendicitis mimicked intussusception, resulting in diagnostic and therapeutic delay and multiple additional imaging studies. OBJECTIVE: To explore the clinical and imaging discriminatory features between the conditions. MATERIALS AND METHODS: Initial US images in six children (age 16 months to 8 years; 4 boys, 2 girls) were reviewed independently and by consensus by three pediatric radiologists. These findings were compared and correlated with the original reports and subsequent US, fluoroscopic, and CT images and reports. RESULTS: All initial US studies demonstrated a multiple-ring-like appearance (target sign, most apparent on transverse views) with diagnostic consensus supportive of intussusception. In three cases, US findings were somewhat discrepant with clinical concerns. Subsequently, four of the six children had contrast enemas; two were thought to have partial or complete intussusception reduction. Three had a repeat US examination, with recognition of the correct diagnosis. None of the US examinations demonstrated definite intralesional lymph nodes or mesenteric fat, but central echogenicity caused by debris/appendicolith was misinterpreted as fat. All showed perilesional hyperechogenicity that, in retrospect, represented inflamed fat "walling off" of the perforated appendix. There were four CTs, all of which demonstrated a double-ring appearance that correlated with the US target appearance, with inner and outer rings representing the dilated appendix and walled-off appendiceal rupture, respectively. All six children had surgical confirmation of perforated appendicitis. CONCLUSION: Contained perforated appendicitis can produce US findings closely mimicking intussusception. Clinical correlation and careful multiplanar evaluation should allow for sonographic suspicion of perforated appendicitis, which can be confirmed on CT if necessary.
Assuntos
Apendicite/diagnóstico por imagem , Erros de Diagnóstico/prevenção & controle , Intussuscepção/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia/métodosRESUMO
Periosteal sleeve fractures, or avulsions of cartilage and/or periosteum with or without an osseous fragment in skeletally immature individuals, are notoriously easy to miss and a high index of suspicion is necessary for accurate diagnosis and treatment. While periosteal sleeve avulsion fractures are classically reported in the patella, they have also been reported in the shoulder, clavicle, and elsewhere in the knee. However, no published reports exist for a periosteal sleeve avulsion fracture in the hand. This case details the first reported instance of such an injury involving a thumb metacarpal in a 3-year-old boy, treated with open reduction and percutaneous pinning of the thumb metacarpal.
RESUMO
ABSTRACT: In recent years, the medical field has recognized the pivotal role of diversity, equity, and inclusion (DEI) in enhancing patient care and addressing health-care disparities. Orthopaedic surgery has embraced these principles to create a more inclusive and representative workforce. A DEI symposium that was sponsored by the American Orthopaedic Association convened orthopaedic surgeons, researchers, educators, and stakeholders to discuss challenges and strategies for implementing DEI initiatives. The symposium emphasized the importance of equity, and fostered conversations on creating equal opportunities and resources. Speakers covered key topics, including establishing DEI divisions, metrics for success, DEI leadership, and available resources, and promoted excellence and innovation in orthopaedic surgery through a more diverse and inclusive approach.
Assuntos
Diversidade Cultural , Ortopedia , Humanos , Ortopedia/organização & administração , Estados Unidos , Disparidades em Assistência à Saúde , Sociedades Médicas , Inclusão Social , Congressos como Assunto , Liderança , Procedimentos OrtopédicosRESUMO
Background: Periacetabular osteotomy (PAO) is a well-established surgical treatment for hip dysplasia, but very few studies report the impact of peri-operative management strategies on early pain and function. The purpose of this study is to describe peri-operative management variability among a group of experienced surgeons and review the literature supporting these practice patterns. Methods: We surveyed 16 surgeons that perform PAO to document various aspects of peri-operative management at four stages: pre-operative, intra-operative, post-operative in the hospital, and at discharge. Our goal was to report current surgical pain management strategies, adjunct medications, type of anesthesia, deep venous thrombosis and heterotopic ossification prophylaxis strategies, initiation of physical therapy, and use of continuous passive motion (CPM). We reviewed current literature to identify studies supporting these perioperative strategies and identify knowledge gaps that would benefit from further investigation. Results: Of the 16 surgeons surveyed, 75% had been in practice greater than 10 years and most had not altered their post-operative protocol for more than 3 years. 15/16 surgeons felt that length of stay could be reduced at their institution with improved peri-operative pain management. 6/16 were considering or had already implemented outpatient PAO as a part of their practice. We found significant variability in the pain medications provided at all peri-operative stages. 14/16 utilized general anesthesia, and many utilized epidural or peripheral nerve blocks. 6/16 surgeons utilized surgical field block (also referred to as periarticular block). These surgeons advocated that surgical field block was an effective intervention with no/minimal complication risk. There is very little literature critically evaluating efficacy of these perioperative management strategies for PAO. Conclusion: There is significant practice variability in peri-operative management of PAO surgery. We report various strategies utilized by a group of experienced surgeons and review supporting literature. There are significant knowledge gaps in best surgical pain management strategies, adjunct medications, surgical field blocks, and use of CPM that need further investigation. Level of Evidence: IV.
Assuntos
Acetábulo , Osteotomia , Assistência Perioperatória , Padrões de Prática Médica , Humanos , Osteotomia/métodos , Acetábulo/cirurgia , Assistência Perioperatória/métodos , Padrões de Prática Médica/estatística & dados numéricos , Manejo da Dor/métodos , Luxação do Quadril/cirurgia , Dor Pós-OperatóriaRESUMO
Mammalian brains vary in size, structure, and function, but the extent to which evolutionarily novel cell types contribute to this variation remains unresolved1-4. Recent studies suggest there is a primate-specific population of striatal inhibitory interneurons, the TAC3 interneurons5. However, there has not yet been a detailed analysis of the spatial and phylogenetic distribution of this population. Here, we profile single cell gene expression in the developing pig (an ungulate) and ferret (a carnivore), representing 94 million years divergence from primates, and assign newborn inhibitory neurons to initial classes first specified during development6. We find that the initial class of TAC3 interneurons represents an ancestral striatal population that is also deployed towards the cortex in pig and ferret. In adult mouse, we uncover a rare population expressing Tac2, the ortholog of TAC3, in ventromedial striatum, prompting a reexamination of developing mouse striatal interneuron initial classes by targeted enrichment of their precursors. We conclude that the TAC3 interneuron initial class is conserved across Boreoeutherian mammals, with the mouse population representing Th striatal interneurons, a subset of which expresses Tac2. This study suggests that initial classes of telencephalic inhibitory neurons are largely conserved and that during evolution, neuronal types in the mammalian brain change through redistribution and fate refinement, rather than by derivation of novel precursors early in development.