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1.
J Pediatr Orthop ; 44(3): e211-e217, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38145396

RESUMO

OBJECTIVE: Developmental dysplasia of the hip is prevalent and is associated with dysplasia of both the femoral head and acetabulum. There is a paucity of literature describing femoral head remodeling after surgical reduction of developmentally dislocated hips. The purpose of this study was to describe and quantify changes in femoral head sphericity after closed or open reduction for developmental dysplasia of the hip. METHODS: A retrospective cohort study was performed including patients with typical developmental hip dislocations who underwent closed or open reduction from 2009 to 2022 at a single institution and had immediate postoperative and average 3-week follow-up magnetic resonance imaging (MRI) scans. A subset of patients also had 3-year follow-up MRI scans. Patients with insufficient imaging or bony procedures at the time of reduction were excluded. We developed a technique to quantify femoral head "sphericity" by comparing differences in measured radii of the femoral head on axial and coronal plane MRI slices. We then calculated the variance of the radii for each plane and averaged these to calculate a combined variance. The variance was used to represent "sphericity," with a larger variance indicating a wider distribution of radii and thus a less spherical shape. RESULTS: A total of 74 patients (69 females) with 96 hips were included in this series. The median age of the child at the time of reduction was 8.7 months [interquartile range (IQR): 2.2]. Over half (58.3%) of the hips had a closed reduction, whereas the remaining were open reduced (41.7%). Immediately postoperatively, at the 3-week time point, and at the 3-year time point the median combined variance was 1.1 (IQR: 3.93), 0.51 (IQR: 1.32), and 0.31 (IQR: 0.50), respectively, indicating improved sphericity over time. CONCLUSIONS: Sphericity of the femoral head in developmental hip dislocations improves in both the immediate postoperative period, as well as the first few years after reduction. Further research is needed to evaluate the mechanism of remodeling, the ideal timing of reduction, and the relationship between femoral head and acetabular remodeling. LEVEL OF EVIDENCE: Level IV-case series, therapeutic study.


Assuntos
Displasia do Desenvolvimento do Quadril , Luxação Congênita de Quadril , Criança , Feminino , Humanos , Lactente , Luxação Congênita de Quadril/cirurgia , Estudos Retrospectivos , Cabeça do Fêmur/cirurgia , Acetábulo/cirurgia , Articulação do Quadril/cirurgia
2.
J Pediatr Orthop ; 44(2): e168-e173, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796167

RESUMO

INTRODUCTION: Social determinants of health have been shown to influence the health and outcomes of pediatric patients. Adolescent idiopathic scoliosis (AIS) may be particularly sensitive to such factors as early diagnosis and treatment can obviate the need for surgical intervention. The purpose of this study was to analyze the effect that social determinants of health have on the severity of AIS at presentation and at the time of surgery. METHODS: A retrospective review was conducted for consecutive patients who underwent posterior spinal fusion for AIS from 2020 to 2022. Demographic data was collected, while insurance status (private vs. public) and childhood opportunity index (COI) categories (LOW vs. HIGH) were used as a proxy for socioeconomic status. Curve magnitude at the initial presentation and at the latest preoperative visit were recorded with a threshold of 25 to 40 degrees considered within the bracing range. Univariate and multivariate analysis was done to compare differences between subgroups as appropriate. RESULTS: A total of 180 patients with mean initial and preoperative major curve angles of 48 and 60 degrees were included. Statistically significant differences in race and insurance types were appreciated, with the LOW COI group having a higher proportion of underrepresented minority and publicly insured patients than the HIGH COI group ( P <0.001). Patients within the LOW COI group presented with an initial curve that was, on average, 6 degrees more severe than those within the HIGH group ( P =0.009) and a preoperative curve that was 4 degrees larger than those within the HIGH group ( P =0.015). Similarly, only 13% of patients within the LOW COI group presented with curves within the bracing threshold, compared with 31% in the HIGH COI group ( P =0.009). CONCLUSION: Socioeconomic status plays a significant role in the severity of AIS. Specifically, patients with lower COI tend to present with curve magnitudes beyond what is responsive to nonsurgical treatment, leading to larger curves at the time of surgery. Future work should focus on addressing social inequalities to optimize the treatment and outcomes of AIS patients. LEVEL OF EVIDENCE: Level III- Retrospective Comparative Study.


Assuntos
Cifose , Escoliose , Fusão Vertebral , Humanos , Adolescente , Criança , Escoliose/cirurgia , Estudos Retrospectivos , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Resultado do Tratamento
3.
J Pediatr Orthop ; 44(5): e400-e405, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38411144

RESUMO

BACKGROUND: Avascular necrosis (AVN) remains the most dreaded complication of unstable slipped capital femoral epiphysis (SCFE) treatment. Newer closed reduction techniques (with perfusion monitoring) have emerged as a technically straightforward means to address residual SCFE deformity while still minimizing the risk of osteonecrosis. However, limited data exists regarding the reliability of intraoperative epiphyseal perfusion monitoring to predict the development of AVN. The purpose of this study was to evaluate its reliability. METHODS: We retrospectively reviewed all patients with unstable SCFE who underwent closed or open reduction with epiphyseal perfusion monitoring using an intracranial pressure (ICP) probe from 2015 to 2023 at a single institution with a minimum 6-month radiographic follow-up. Demographic, clinical, and radiographic data were recorded, including duration of symptoms, type of reduction, capsulotomy performed, presence of a waveform on ICP monitoring after epiphyseal fixation, and development of AVN on follow-up radiographs. RESULTS: Our cohort included 33 hips (32 patients), of which 60.6% (n=20) were male. The average age was 12.5±1.8 years, with a median follow-up of 15.8 months. Eleven hips were treated with open reduction using the modified Dunn technique (10 hips) or anterior approach (1 hip), and 22 hips were treated with inadvertent (5 hips) or purposeful closed reduction using the Leadbetter technique (17 hips). Overall, 8 of the 33 hips in our series (24.2%) developed AVN, 6 of which (20%) had a pulsatile waveform on intraoperative epiphyseal perfusion monitoring. The overall rate of AVN after closed reductions was 31.8% (7 of 22 hips); the incidence of AVN after closed reduction with a detectable waveform was 30% (6 of 20 hips). There was no significant association between time to surgery ( P =0.416) or type of reduction ( P =0.218) and the incidence of AVN. CONCLUSIONS: In this series, intraoperative epiphyseal perfusion monitoring did not reliably predict the development of osteonecrosis. To our knowledge, this is the first study to report AVN after demonstrable intraoperative epiphyseal perfusion following closed reduction of unstable slips. LEVEL OF EVIDENCE: Level IV: case series-therapeutic study.


Assuntos
Necrose da Cabeça do Fêmur , Escorregamento das Epífises Proximais do Fêmur , Humanos , Masculino , Criança , Adolescente , Feminino , Escorregamento das Epífises Proximais do Fêmur/cirurgia , Estudos Retrospectivos , Reprodutibilidade dos Testes , Necrose da Cabeça do Fêmur/etiologia , Necrose da Cabeça do Fêmur/epidemiologia , Perfusão/efeitos adversos , Resultado do Tratamento
4.
J Pediatr Orthop ; 44(3): 151-156, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38062866

RESUMO

BACKGROUND: The aim of this study is to assess the rate of distal ulnar growth arrest following physeal fracture and to identify specific risk factors for premature physeal closure. METHODS: A retrospective review of patients with a distal ulnar physeal fracture was performed at a single United States children's hospital. Patients without 6-month follow-up were excluded. Patient demographics, injury characteristics, treatment, and outcomes were abstracted. Fractures were classified by the Salter-Harris (SH) system. All follow-up radiographs were reviewed for changes in ulnar variance or signs of premature physeal arrest. RESULTS: Fifty-six children with distal ulnar physeal fracture at a mean age of 10.7±3.3 years were included with a mean follow-up of 1.9 years. The most common fracture pattern was a SH II (52.7%), versus SH I (29.1%), SH III (9.1%), and SH IV (9.1%). Of displaced fractures (41.1%), the mean translation was 40.2±38.3% the and mean angulation was 24.8±20.9 degrees. Eleven fractures (19.6%) demonstrated radiographic signs of growth disturbance, including 3 patients (5.4%) with growth disturbance but continued longitudinal growth and 8 patients (14.3%) with complete growth arrest. The average ulnar variance was -3.4 mm. Three patients underwent subsequent surgical reconstruction including ulnar lengthening with an external fixator, distal ulna completion epiphysiodesis with distal radius epiphysiodesis, and ulnar corrective osteotomy. Patients with displaced fractures and SH III/IV fractures were more likely to develop a growth disturbance (34.8% vs. 3.2%, P =0.003; 50.0% vs. 11.1%, P =0.012, respectively). Children with less than 2 years of skeletal growth remaining at the time of injury had a higher risk of growth disturbance (46.2% vs. 9.5%, P =0.007). CONCLUSIONS: SH III and IV fractures are more common injury patterns in the distal ulna compared with the distal radius. Growth disturbance or growth arrest occurs in ~20% of distal ulnar physeal fractures. Displaced fractures, intra-articular fractures, fractures requiring open reduction, and older children are at increased risk of distal ulnar growth arrest and should be followed more closely. LEVEL OF EVIDENCE: Level IV--case series.


Assuntos
Fraturas Múltiplas , Fraturas do Rádio , Fraturas Salter-Harris , Fraturas da Ulna , Criança , Humanos , Adolescente , Fraturas do Rádio/cirurgia , Incidência , Ulna/cirurgia , Rádio (Anatomia)/cirurgia , Lâmina de Crescimento , Fraturas da Ulna/terapia , Estudos Retrospectivos
5.
J Pediatr Orthop ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39279747

RESUMO

BACKGROUND: Patellofemoral instability (PFI) is a common problem with various anatomic risk factors identified, including patella alta as one of the most powerful predictors. Given that the medial patellofemoral ligament (MPFL) is the primary soft tissue stabilizer of the patella, a common procedure to treat recurrent patellar instability is MPFL reconstruction. The aim of this study is to examine the relationship between MPFL reconstruction and patellar height. We hypothesize that after reconstruction, patellar instability patients would have demonstrable reduction in patella height and patella alta correction. METHODS: Patient records were queried for patients who underwent MPFL reconstruction for recurrent patellar instability. Patient and operative demographics were collected. We measured Insall-Salvati ratio (ISR), Caton Deschamps index (CDI), and Blackburne-Peel ratio (BPR) in all patients at various time points. The height indices were compared across the preoperative, immediately postoperative, and 6-month time points in a pairwise fashion using paired-sample t-tests. Further subgroup analysis of patients (n=27) with elevated preoperative Caton Deschamps Index (defined as >1.3) was completed. RESULTS: The final cohort was 103 patients. There was a significant difference between pre- and postoperative ISR (P<0.001) and at 6-month follow up (P<0.001), between preoperative CDI and the 6-month follow-up (P<0.0010), and between the postoperative and preoperative CDI (P<0.001). There was also a difference between preoperative and postoperative BPR (P<0.001), as well as between the preoperative and 6-month follow-up BPR (P=0.002). Twenty-seven patients had an initial CDI greater than 1.3. Differences were observed between pre- and postoperative mean CDI (P=0.001) and at 6-month follow-up (P=0.006), between both postoperative and 6-month ISR (both P<0.001), and preoperative mean BPR and the postoperative (P=0.004) and 6-month mean BPR (P=0.027). CONCLUSIONS: Patients with pre-existing patella alta and recurrent patella dislocations who undergo isolated MPFL reconstruction have decreased patella alta at their 6-month follow-up as measured by ISR, CDI, and BPR. Patients without patella alta do not demonstrate statistically significant differences after their MPFL reconstruction. LEVEL OF EVIDENCE: III (retrospective comparative study).

6.
J Pediatr Orthop ; 42(10): 614-620, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36017946

RESUMO

BACKGROUND: Despite recent policy efforts to increase price transparency, obtaining estimated prices for surgery remains difficult for most patients and families. PURPOSE: Assess availability and variability of cost and self-pay discounts for pediatric anterior cruciate ligament (ACL) reconstruction in the United States. METHODS: This was a prospective study using scripted telephone calls to obtain price estimates and self-pay discounts for pediatric ACL reconstruction. From July to August 2020, investigators called 102 hospitals, 51 "top-ranked" pediatric orthopaedic hospitals and 51 "non-top ranked" hospitals randomly selected, to impersonate the parent of an uninsured child with a torn ACL. Hospital, surgeon, and anesthesia price estimates, availability of a self-pay discount, and number of calls and days required to obtain price estimates were recorded for each hospital. Hospitals were compared on the basis of ranking, teaching status, and region. RESULTS: Only 31/102 (30.3%) hospitals provided a complete price estimate. Overall, 52.9% of top-ranked hospitals were unable to provide any price information versus 31.4% of non-top-ranked hospitals ( P =0.027). There was a 6.1-fold difference between the lowest and highest complete price estimates (mean estimate $29,590, SD $14,975). The mean complete price estimate for top-ranked hospitals was higher than for non-top-ranked hospitals ($34,901 vs. $25,207; P =0.07). The mean complete price estimate varied significantly across US region ( P =0.014), with the greatest mean complete price in the Northeast ($41,812). Altogether, 38.2% hospitals specified a self-pay discount, but only a fraction disclosed exact dollar or percentage discounts. The mean self-pay discount from top-ranked hospitals was larger than that of non-top-ranked hospitals ($18,305 vs. $9902; P =0.011). An average of 3.1 calls (range 1.0 to 12.0) over 5 days (range 1 to 23) were needed to obtain price estimates. CONCLUSION: Price estimates for pediatric sports medicine procedures can be challenging to obtain, even for the educated consumer. Top-ranked hospitals and hospitals in the Northeast region may charge more than their counterparts. In all areas, self-pay discounts can be substantial if they can be identified but they potentially create an information disadvantage for unaware patients needing to pay out-of-pocket. STUDY DESIGN: Economic; Level of Evidence II. WHAT IS KNOWN ABOUT THE SUBJECT: Previous studies have highlighted the importance of value-based health care decisions and deficits of price transparency in various fields including pediatric and orthopaedics procedures. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE: This study is the first to examine availability and variability of health care cost in pediatric sports medicine and the first to assess availability and magnitude of self-pay discounts, setting expectations for the uninsured patient incurring large out-of-pocket expenses.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Criança , Custos de Cuidados de Saúde , Hospitais Pediátricos , Humanos , Estudos Prospectivos , Estados Unidos
7.
Spine Deform ; 12(6): 1683-1687, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38977658

RESUMO

PURPOSE: The psychological effects of scoliosis bracing can be difficult, and thus clinicians sometimes recommend a brace holiday when the curve corrects to less than 25°. However, the clinical indications for taking a break from the brace before reaching maturity have yet to be described. We hypothesized there would be a relationship between brace holiday eligibility and degree of curve at presentation, change in curve magnitude while bracing, and level of bracing compliance. METHODS: A retrospective cohort study at a single institution was performed from 2016 to 2022. Objective brace compliance I-button data were collected on patients aged 3-9 years old. Patients with other etiologies besides idiopathic scoliosis before the age of 10 were excluded. Binary logistic regression was performed to determine the effect of significant variables on the likelihood of brace holiday. RESULTS: Fifty-six patients met inclusion criteria. Of these, 20 were able to get a brace holiday. Patients with higher brace compliance and larger in-brace curve correction were more likely to get a brace holiday (P = 0.015, 0.004). Patients with higher BMIs and larger curves at initial presentation were less likely to get a brace holiday (P = 0.002, 0.014). CONCLUSION: Compliant brace wearers with good in-brace correction are most likely to be eligible for a brace holiday. While some elements remain immutable, others are modifiable, such as bracing compliance. Understanding how outcomes differ between patients who do and do not take a brace holiday will be crucial to elucidating if the psychological benefit of taking a break from the brace can be justified.


Assuntos
Braquetes , Cooperação do Paciente , Escoliose , Humanos , Escoliose/terapia , Escoliose/psicologia , Criança , Estudos Retrospectivos , Feminino , Masculino , Pré-Escolar , Férias e Feriados
8.
Orthop J Sports Med ; 12(9): 23259671241248433, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39351066

RESUMO

Background: Research at the intersection between social determinants of health (SDOH) and orthopaedics remains an area of active exploration, with recent literature demonstrating significant disparities in a wide array of orthopaedic outcomes in patients with different SDOH. Purpose/Hypothesis: The purpose of this study was to use a validated composite measure of SDOH mapped to census tracts (Child Opportunity Index [COI]) to explore disparities in functional outcomes after anterior cruciate ligament (ACL) reconstruction. It was hypothesized that patients with a lower COI score would have delayed surgical care and worse functional outcomes after ACL reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: Demographic, surgical, and functional outcomes data were extracted for all patients aged ≤18 years who underwent primary ACL reconstruction at our institution between 2009 and 2019. Strength deficits were calculated, and COI quintile scores were obtained. One-way analysis of variance, the chi-square test, and the Fisher exact test were used to compare variables of interest between the lower 2 quintiles (low group) and the upper 2 quintiles (high group). Results: Of the 1027 patients, 226 (22.0%) were in the low group, while 801 (78.0%) were in the high group. There was a significantly greater time from injury to surgery in the low group than in the high group (98.15 ± 102.65 vs 71.79 ± 101.88 days, respectively; P < .001). The low group had a significantly lower extension-flexion range of motion at 1- and 3-month follow-up (P = .03 and P = .02, respectively) but no difference at 6-month follow-up (P = .27). The low group attended fewer physical therapy visits than the high group (24.82 ± 10.55 vs 37.81 ± 18.07, respectively; P < .001). The low group had significant deficits in quadriceps strength at 3, 6, and 9 months at 180 deg/s (P = .03, P < .001, and P = .01, respectively) and at 6 months at 300 deg/s (P = .002). Conclusion: In this study, we found that the COI was associated with disparities in key clinical outcomes including time to surgery, postoperative range of motion, and postoperative strength.

9.
Sports Health ; : 19417381231198541, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37768038

RESUMO

BACKGROUND: A decrease in sport-related injuries was observed in 2020, which has been attributed to COVID-19 and recommendations to suspend organized sports. In adult populations, increased injury rates have been noted in athletes returning to play after an extended period of reduced play, attributable to deconditioning. There is growing literature surrounding concern over increased injury risk after return to sport after the COVID-19 shutdowns. HYPOTHESIS: Like adults, pediatric patients experience an increase in sport-related injuries after periods of "deconditioning," such as during the COVID-19 shutdown. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 4. METHODS: The Consumer Product Safety Commission's National Electronic Injury Surveillance System database was queried to identify 13- to 18-year-old patients who sustained a sprain/strain type injury in 2019 or 2021 to an extremity, and involved sporting equipment for basketball, baseball/softball, soccer, and football. The control group was established as patients who sustained injury in 2019, and the post-COVID-19 group was established as those in 2021. Quantity of injuries sustained in these 2 groups were compared and analyzed by subgroup. RESULTS: There was a significant difference in the total number of sport-related sprains/strains in 2019 versus 2021 (P = 0.01), with more injuries in 2019 (n = 151,067) than in 2021 (n = 104,041). There were more injuries in boys than in girls. Proportion of injuries by sports were similar in both time periods. There was a significant decrease in basketball-related injuries by 21% (P ≤ 0.01, relative risk ratio [rrr] = 0.7979) and a significant increase in football-related injuries by 14% (P = 0.01, rrr = 1.1404) and in soccer injuries by 14.2% (P = 0.03, rrr = 1.1422). CONCLUSION: There is significant heterogeneity in injury rates by sports, with no conclusive increase in injuries, contrary to expectations. CLINICAL RELEVANCE: This study suggests that the relationship between deconditioning and injury may be less clear in the child-athlete, and gives recommendations for return to sport after extended breaks. STRENGTH-OF-RECOMMENDATION TAXONOMY (SORT): Level 2c.

10.
J Child Orthop ; 17(3): 259-267, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37288049

RESUMO

Purpose: Given that pediatric traumatic hip dislocations are relatively rare, the purpose of the current study is twofold: first, to contribute a significant cohort to the existing corpus, and second, to provide evidence toward the role that computed tomography and magnetic resonance imaging could play in identification and management of this type of injury. Methods: A retrospective review was conducted of all patients with traumatic hip dislocation who presented from 2012 to 2022 at a tertiary-level pediatric trauma center. Data regarding demographics, mechanism of injury, imaging, and treatment were tabulated. Outcomes of interest included immobilization length, concomitant injuries, imaging performed and findings, and rates of avascular necrosis, pain, and stiffness. Concomitant injuries were identified using imaging, clinical, and operative notes. Differences between categorical variables were compared using chi-square analysis or Fischer-exact testing, while continuous variables were compared using Student t tests or Wilcoxon rank sum tests when appropriate. Results: Thirty-four patients were identified. Postreduction, 28 patients had a cumulative 17 magnetic resonance imaging, 19 computed tomographies, and 1 intraoperative arthrogram. Of these, 16 patients had 19 injuries identified on advanced imaging that were missed on initial radiographs. Eleven of these patients went on to operative treatment. In eight of these, postreduction advanced imaging helped guide the decision for surgery. In four patients, magnetic resonance imaging was necessary to fully characterize injury to the posterior acetabular rim after initial identification on computed tomography. Magnetic resonance imaging was also used to rule out one computed tomography-diagnosed acetabular fracture. Conclusion: Magnetic resonance imaging is valuable to fully define associated rim and intra-articular injuries following initial treatment of pediatric traumatic hip dislocations. Level of evidence: Level IV diagnostic study.

11.
Clin Biomech (Bristol, Avon) ; 105: 105975, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37127006

RESUMO

BACKGROUND: We aimed to biomechanically evaluate the distal pronator quadratus and compare two locations of distal transection on the strength of the subsequent repair. METHODS: Eighteen fresh-frozen cadaveric specimens were dissected to the pronator quadratus muscle. Specimens were randomly allocated for transection of the pronator quadratus at the myotendinous junction (red group) or parallel to the myotendinous junction at the midsection of the distal tendinous zone (white group). For both groups, repair of the muscle was performed using two figure-of-8 sutures. The radius and ulna were positioned in 90° of wrist extension. The proximal muscular pronator quadratus was fixed in a cryo-clamp. Load-to-failure testing of the repair was performed at 1 mm/s with maximum amount of force applied to the pronator quadratus recorded for each specimen. FINDINGS: The pronator quadratus had a mean width, height, and area of 31.41 ± 5.74 mm, 53.79 ± 7.46 mm, and 1604.27 ± 429.20 mm2 respectively. The pronator quadratus distal tendinous zone had a mean width, height, and area of 29.71 ± 5.83 mm, 12.22 ± 2.79 mm, 282.94 ± 148.30 mm2 respectively. There was no significant difference between the two groups for pronator quadratus height, width, total area, or tendinous zone height, width, or total area. The average load to failure for the white group was significantly higher than that of the red group (29.46 ± 4.24 N vs. 13.78 N ± 6.66 N). INTERPRETATION: Incision and repair of the pronator quadratus in the distal tendinous region is stronger than incision and repair at the red myotendinous junction of the distal PQ.


Assuntos
Fraturas do Rádio , Fraturas do Punho , Humanos , Placas Ósseas , Cadáver , Antebraço , Fixação Interna de Fraturas , Músculo Esquelético/cirurgia , Fraturas do Rádio/cirurgia
12.
Dev Cell ; 58(10): 898-914.e7, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37071996

RESUMO

Cardiomyocyte differentiation continues throughout murine gestation and into the postnatal period, driven by temporally regulated expression changes in the transcriptome. The mechanisms that regulate these developmental changes remain incompletely defined. Here, we used cardiomyocyte-specific ChIP-seq of the activate enhancer marker P300 to identify 54,920 cardiomyocyte enhancers at seven stages of murine heart development. These data were matched to cardiomyocyte gene expression profiles at the same stages and to Hi-C and H3K27ac HiChIP chromatin conformation data at fetal, neonatal, and adult stages. Regions with dynamic P300 occupancy exhibited developmentally regulated enhancer activity, as measured by massively parallel reporter assays in cardiomyocytes in vivo, and identified key transcription factor-binding motifs. These dynamic enhancers interacted with temporal changes of the 3D genome architecture to specify developmentally regulated cardiomyocyte gene expressions. Our work provides a 3D genome-mediated enhancer activity landscape of murine cardiomyocyte development.


Assuntos
Elementos Facilitadores Genéticos , Miócitos Cardíacos , Animais , Camundongos , Cromatina , Regiões Promotoras Genéticas , Transcriptoma
13.
Nat Commun ; 12(1): 4442, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290256

RESUMO

The forward genetic screen is a powerful, unbiased method to gain insights into biological processes, yet this approach has infrequently been used in vivo in mammals because of high resource demands. Here, we use in vivo somatic Cas9 mutagenesis to perform an in vivo forward genetic screen in mice to identify regulators of cardiomyocyte (CM) maturation, the coordinated changes in phenotype and gene expression that occur in neonatal CMs. We discover and validate a number of transcriptional regulators of this process. Among these are RNF20 and RNF40, which form a complex that monoubiquitinates H2B on lysine 120. Mechanistic studies indicate that this epigenetic mark controls dynamic changes in gene expression required for CM maturation. These insights into CM maturation will inform efforts in cardiac regenerative medicine. More broadly, our approach will enable unbiased forward genetics across mammalian organ systems.


Assuntos
Epigênese Genética , Miócitos Cardíacos/fisiologia , Ubiquitina-Proteína Ligases/metabolismo , Animais , Animais Recém-Nascidos , Sistemas CRISPR-Cas , Regulação da Expressão Gênica no Desenvolvimento , Histonas/metabolismo , Camundongos , Mutagênese , Miócitos Cardíacos/metabolismo , Fenótipo , Reprodutibilidade dos Testes , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
14.
Am J Sports Med ; 49(14): 3937-3944, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34723684

RESUMO

BACKGROUND: Current literature reports highly satisfactory short- and midterm clinical outcomes in patients with arthroscopic 270° labral tear repairs. However, data remain limited on long-term clinical outcomes and complication and redislocation rates in patients with traumatic shoulder instability involving anterior, inferior, and posterior labral injury. PURPOSE: To investigate, at a minimum follow-up of 10 years, the clinical outcomes, complications, and recurrent instability in patients with 270° labral tears involving the anterior, inferior, and posterior labrum treated with arthroscopic stabilization using suture anchors. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective outcomes study was completed for all patients with a minimum 10-year follow-up who underwent arthroscopic 270° labral tear repairs with suture anchors by a single surgeon. Outcome measures included pre- and postoperative Rowe score, American Shoulder and Elbow Surgeons (ASES) score, Simple Shoulder Test, visual analog scale for pain, and Single Assessment Numeric Evaluation (SANE). Western Ontario Shoulder Instability Index (WOSI) scores were collected postoperatively. Complication data were collected, including continued instability, subluxation or dislocation events, and revision surgery. Failure was defined as any cause of revision surgery. RESULTS: In total, 21 patients (mean ± SD age, 27.1 ± 9.6 years) with 270° labral repairs were contacted at a minimum 10-year follow-up. All outcome measures showed statistically significant improvements as compared with those preoperatively: Rowe (53.9 ± 11.4 to 88.7 ± 8.9; P = .005), ASES (72.9 ± 18.4 to 91.8 ± 10.8; P = .004), Simple Shoulder Test (8.7 ± 2.4 to 11.2 ± 1.0; P = .013), visual analog scale (2.5 ± 2.6 to 0.5 ± 1.1; P = .037), and SANE (24.0 ± 15.2 to 91.5 ± 8.3; P = .043). The mean postoperative WOSI score at minimum follow-up was 256.3 ± 220.6. Three patients had postoperative complications, including a traumatic subluxation, continued instability, and a traumatic dislocation, 2 of which required revision surgery (14.2% failure rate). CONCLUSION: Arthroscopic repairs of 270° labral tears involving the anterior, inferior, and posterior labrum have highly satisfactory clinical outcomes at 10 years, with complication and redislocation rates similar to those reported at 2 years. This suggests that repairs of extensile labral tears are effective in restoring and maintaining mechanical stability of the glenohumeral joint in the long term.


Assuntos
Instabilidade Articular , Lesões do Ombro , Articulação do Ombro , Adolescente , Adulto , Artroscopia , Humanos , Instabilidade Articular/cirurgia , Estudos Retrospectivos , Ombro , Articulação do Ombro/cirurgia , Resultado do Tratamento , Adulto Jovem
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