Intraoperative Epiphyseal Perfusion Monitoring Does Not Reliably Predict Osteonecrosis Following Treatment of Unstable SCFE.

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.

Femoral Head Remodeling After Surgical Reduction of Developmental Hip Dislocations.

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.

Location of distal pronator quadratus repair in distal radius fractures: A cadaveric biomechanical study.

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.

Dynamic changes in P300 enhancers and enhancer-promoter contacts control mouse cardiomyocyte maturation.

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.

Massively parallel in vivo CRISPR screening identifies RNF20/40 as epigenetic regulators of cardiomyocyte maturation.

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.