Mapping transcriptomic vector fields of single cells.

Single-cell (sc)RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires kinetic models capable of unveiling governing regulatory functions. Here, we introduce an analytical framework dynamo (https://github.com/aristoteleo/dynamo-release), which infers absolute RNA velocity, reconstructs continuous vector fields that predict cell fates, employs differential geometry to extract underlying regulations, and ultimately predicts optimal reprogramming paths and perturbation outcomes. We highlight dynamo's power to overcome fundamental limitations of conventional splicing-based RNA velocity analyses to enable accurate velocity estimations on a metabolically labeled human hematopoiesis scRNA-seq dataset. Furthermore, differential geometry analyses reveal mechanisms driving early megakaryocyte appearance and elucidate asymmetrical regulation within the PU.1-GATA1 circuit. Leveraging the least-action-path method, dynamo accurately predicts drivers of numerous hematopoietic transitions. Finally, in silico perturbations predict cell-fate diversions induced by gene perturbations. Dynamo, thus, represents an important step in advancing quantitative and predictive theories of cell-state transitions.

Evolutionary Selection and Constraint on Human Knee Chondrocyte Regulation Impacts Osteoarthritis Risk.

During human evolution, the knee adapted to the biomechanical demands of bipedalism by altering chondrocyte developmental programs. This adaptive process was likely not without deleterious consequences to health. Today, osteoarthritis occurs in 250 million people, with risk variants enriched in non-coding sequences near chondrocyte genes, loci that likely became optimized during knee evolution. We explore this relationship by epigenetically profiling joint chondrocytes, revealing ancient selection and recent constraint and drift on knee regulatory elements, which also overlap osteoarthritis variants that contribute to disease heritability by tending to modify constrained functional sequence. We propose a model whereby genetic violations to regulatory constraint, tolerated during knee development, lead to adult pathology. In support, we discover a causal enhancer variant (rs6060369) present in billions of people at a risk locus (GDF5-UQCC1), showing how it impacts mouse knee-shape and osteoarthritis. Overall, our methods link an evolutionarily novel aspect of human anatomy to its pathogenesis.

Ageing hallmarks exhibit organ-specific temporal signatures.

Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Although major categories of ageing damage have been identified-such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function1-these deleterious processes interact with extraordinary complexity within and between organs, and a comprehensive, whole-organism analysis of ageing dynamics has been lacking. Here we performed bulk RNA sequencing of 17 organs and plasma proteomics at 10 ages across the lifespan of Mus musculus, and integrated these findings with data from the accompanying Tabula Muris Senis2-or 'Mouse Ageing Cell Atlas'-which follows on from the original Tabula Muris3. We reveal linear and nonlinear shifts in gene expression during ageing, with the associated genes clustered in consistent trajectory groups with coherent biological functions-including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Notably, these gene sets show similar expression across tissues, differing only in the amplitude and the age of onset of expression. Widespread activation of immune cells is especially pronounced, and is first detectable in white adipose depots during middle age. Single-cell RNA sequencing confirms the accumulation of T cells and B cells in adipose tissue-including plasma cells that express immunoglobulin J-which also accrue concurrently across diverse organs. Finally, we show how gene expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to the ageing of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of ageing, providing a foundation from which to track systemic sources of declining health at old age.

Compliant Clients: Catechols Exhibit Enhanced Solubility and Stability in Diverse Complex Coacervates.

Polyelectrolyte coacervates, with their greater-than-water density, low interfacial energy, shear thinning viscosity, and ability to undergo structural arrest, mediate the formation of diverse load-bearing macromolecular materials in living organisms as well as in industrial material fabrication. Coacervates, however, have other useful attributes that are challenging to study given the metastability of coacervate colloidal droplets and a lack of suitable analytical methods. We adopt solution electrochemistry and nuclear magnetic resonance measurements to obtain remarkable insights about coacervates as solvent media for low-molecular-weight catechols. When catechols are added to dispersions of coacervated polyelectrolytes, there are two significant consequences: (1) catechols preferentially partition up to 260-fold into the coacervate phase, and (2) coacervates stabilize catechol redox potentials by up to +200 mV relative to the equilibrium solution. The results suggest that the relationship between phase-separated polyelectrolytes and their client molecules is distinct from that existing in aqueous solution and has the potential for insulating many redox-unstable chemicals.

Effects of joint loading on the development of capital femoral epiphysis morphology.

INTRODUCTION: The deleterious influence of increased mechanical forces on capital femoral epiphysis development is well established; however, the growth of the physis in the absence of such forces remains unclear. The hips of non-ambulatory cerebral palsy (CP) patients provide a weight-restricted (partial weightbearing) model which can elucidate the influence of decreased mechanical forces on the development of physis morphology, including features related to development of slipped capital femoral epiphysis (SCFE). Here we used 3D image analysis to compare the physis morphology of children with non-ambulatory CP, as a model for abnormal hip loading, with age-matched native hips. MATERIALS AND METHODS: CT images of 98 non-ambulatory CP hips (8-15 years) and 80 age-matched native control hips were used to measure height, width, and length of the tubercle, depth, width, and length of the metaphyseal fossa, and cupping height across different epiphyseal regions. The impact of age on morphology was assessed using Pearson correlations. Mixed linear model was used to compare the quantified morphological features between partial weightbearing hips and full weightbearing controls. RESULTS: In partial weightbearing hips, tubercle height and length along with fossa depth and length significantly decreased with age, while peripheral cupping height increased with age (r > 0.2, P < 0.04). Compared to normally loaded (full weightbearing) hips and across all age groups, partially weightbearing hips' epiphyseal tubercle height and length were smaller (P < .05), metaphyseal fossa depth was larger (P < .01), and posterior, inferior, and anterior peripheral cupping heights were smaller (P < .01). CONCLUSIONS: Smaller epiphyseal tubercle and peripheral cupping with greater metaphyseal fossa size in partial weightbearing hips suggests that the growing capital femoral epiphysis requires mechanical stimulus to adequately develop epiphyseal stabilizers. Deposit low prevalence and relevance of SCFE in CP, these findings highlight both the role of normal joint loading in proper physis development and how chronic abnormal loading may contribute to various pathomorphological changes of the proximal femur (i.e., capital femoral epiphysis).

What Are the Early Outcomes of True Reverse Periacetabular Osteotomy for Symptomatic Hip Overcoverage?

BACKGROUND: Acetabular overcoverage is associated with pincer-type femoroacetabular impingement (FAI). A subtype of acetabular overcoverage is caused by a deep acetabulum with a negatively tilted acetabular roof, in which acetabular reorientation may be a preferable alternative to rim trimming to uncover the femoral head. We introduced the true reverse periacetabular osteotomy (PAO) in 2003, which in contrast to an anteverting PAO, also flexes and abducts the acetabulum relative to the intact ilium to decrease anterior and lateral femoral head coverage and correct negative tilt of the acetabular roof. To our knowledge, the clinical results of the true reverse PAO have not been evaluated. QUESTIONS/PURPOSES: For a group of patients who underwent reverse PAO, (1) Do patients undergoing reverse PAO demonstrate short-term improvement in pain, function, and hip ROM, and decreased acetabular coverage, as defined by lateral and anterior center-edge angle and Tönnis angle? (2) Are there identifiable factors associated with success or adverse outcomes of reverse PAO as defined by reoperation, conversion to THA, or poor patient-reported outcome scores? (3) Are there identifiable factors associated with early complications? METHODS: Between 2003 and 2017, two surgeons carried out 49 reverse PAOs in 37 patients. Twenty-five patients had unilateral reverse PAO and 12 patients had staged, bilateral reverse PAOs. To ensure that each hip was an independent data point for statistical analysis, we chose to include in our series only the first hip in the patients who had bilateral reverse PAOs. During the study period, our general indications for this operation were symptomatic lateral and anterior acetabular overcoverage causing FAI that had failed to respond to previous conservative or surgical treatment. Thirty-seven hips in 37 patients with a median (range) age of 18 years (12 to 41; interquartile range 16 to 21) were included in this retrospective study at a minimum follow-up of 2 years (median 6 years; range 2 to 17). Thirty-four patients completed questionnaires, 24 patients had radiographic evaluation, and 23 patients received hip ROM clinical examination. However, seven patients had not been seen in more than 5 years. The clinical and radiographic parameters of all 37 hips that underwent reverse PAO in 37 patients from a longitudinally maintained institutional database were retrospectively studied preoperatively and postoperatively. Adverse outcomes were considered conversion to THA or a WOMAC pain score greater than 10 at least 2 years postoperatively. Patient-reported outcomes, radiographic measurements, and hip ROM were evaluated preoperatively and at most recent follow-up using a paired t-test or McNemar test, as appropriate. Linear regression analysis was used to assess for identifiable factors associated with clinical outcomes. Logistic regression analysis was used to assess for identifiable factors associated with adverse outcomes and surgical complications. All tests were two-sided, and p values less than 0.05 were considered significant. RESULTS: At a minimum of 2 years after reverse PAO, patients experienced improvement in WOMAC pain (-7 [95% CI -9 to -5]; p < 0.001), stiffness (-2 [95% CI -3 to -1]; p < 0.001), and function scores (-18 [95% CI -24 to -12]; p < 0.001) and modified Harris Hip Score (mHHS) (20 [95% CI 13 to 27]; p < 0.001). The mean postoperative hip ROM improved in internal rotation (8° [95% CI 2° to 14°]; p = 0.007). Acetabular coverage, as defined by lateral center-edge angle (LCEA), anterior center-edge angle (ACEA), and Tönnis angle, improved by -8° (95% CI -12° to -5°; p < 0.001) for LCEA, -12° (95% CI -15° to -9°; p < 0.001) for ACEA, and 9° (95% CI 6° to 13°; p < 0.001) for Tönnis angle. The postoperative severity of radiographic arthritis was associated with worse WOMAC function scores such that for each postoperative Tönnis grade, WOMAC function score increased by 12 points (95% CI 2 to 22; p = 0.03). A greater postoperative Tönnis grade was also correlated with worse mHHS, with an average decrease of 12 points (95% CI -20 to -4; p = 0.008) in mHHS for each additional Tönnis grade. Presence of a positive postoperative anterior impingement test was associated with a decrease in mHHS score at follow-up, with an average 23-point decrease in mHHS (95% CI -34 to -12; p = 0.001). Nineteen percent (7 of 37) of hips had surgery-related complications. Four hips experienced adverse outcomes at final follow-up, with two patients undergoing subsequent THA and two with a WOMAC pain score greater than 10. We found no factors associated with complications or adverse outcomes. CONCLUSION: The early clinical and radiographic results of true reverse PAO compare favorably to other surgical treatments for pincer FAI, suggesting that reverse PAO is a promising treatment for cases of pincer FAI caused by global acetabular overcoverage. However, it is a technically complex procedure that requires substantial training and preparation by a surgeon who is already familiar with standard PAO, and it must be carefully presented to patients with discussion of the potential risks and benefits. Future studies are needed to further refine the indications and to determine the long-term outcomes of reverse PAO. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Does the Capital Femoral Physis Bony MorphologyDiffer in Children with Symptomatic Cam-type Femoroacetabular Impingement.

BACKGROUND: The epiphyseal tubercle, the corresponding metaphyseal fossa, and peripheral cupping are key stabilizers of the femoral head-neck junction. Abnormal development of these features in the setting of supraphysiologic physeal stress under high forces (for example, forces that occur during sports activity) may result in a cam morphology. Although most previous studies on cam-type femoroacetabular impingement (FAI) have mainly focused on overgrowth of the peripheral cupping, little is known about detailed morphologic changes of the epiphyseal and metaphyseal bony surfaces in patients with cam morphology. QUESTIONS/PURPOSES: (1) Does the CT-based bony morphology of the peripheral epiphyseal cupping differ between patients with a cam-type morphology and asymptomatic controls (individuals who did not have hip pain)? (2) Does the CT-based bony morphology of the epiphyseal tubercle differ between patients with a cam-type morphology and asymptomatic controls? (3) Does the CT-based bony morphology of the metaphyseal fossa differ between patients with a cam-type morphology and asymptomatic controls? METHODS: After obtaining institutional review board approval for this study, we retrospectively searched our institutional database for patients aged 8 to 15 years with a diagnosis of an idiopathic cam morphology who underwent a preoperative CT evaluation of the affected hip between 2005 and 2018 (n = 152). We excluded 96 patients with unavailable CT scans and 40 patients with prior joint diseases other than cam-type FAI. Our search resulted in 16 patients, including nine males. Six of 16 patients had a diagnosis of bilateral FAI, for whom we randomly selected one side for the analysis. Three-dimensional (3-D) models of the proximal femur were generated to quantify the size of the peripheral cupping (peripheral growth of the epiphysis around the metaphysis), epiphyseal tubercle (a beak-like prominence in the posterosuperior aspect of the epiphysis), and metaphyseal fossa (a groove on the metaphyseal surface corresponding to the epiphyseal tubercle). A general linear model was used to compare the quantified anatomic features between the FAI cohort and 80 asymptomatic hips (aged 8 to 15 years; 50% male) after adjusting for age and sex. A secondary analysis using the Wilcoxon matched-pairs signed rank test was performed to assess side-to-side differences in quantified morphological features in 10 patients with unilateral FAI. RESULTS: After adjusting for age and sex, we found that patients with FAI had larger peripheral cupping in the anterior, posterior, superior, and inferior regions than control patients who did not have hip symptoms or radiographic signs of FAI (by 1.3- to 1.7-fold; p < 0.01 for all comparisons). The epiphyseal tubercle height and length were smaller in patients with FAI than in controls (by 0.3- to 0.6-fold; p < 0.02 for all comparisons). There was no difference in tubercle width between the groups. Metaphyseal fossa depth, width, and length were larger in patients with FAI than in controls (by 1.8- to 2.3-fold; p < 0.001 for all comparisons). For patients with unilateral FAI, we saw similar peripheral cupping but smaller epiphyseal tubercle (height and length) along with larger metaphyseal fossa (depth) in the FAI side compared with the uninvolved contralateral side. CONCLUSION: Consistent with prior studies, we observed more peripheral cupping in patients with cam-type FAI than control patients without hip symptoms or radiographic signs of FAI. Interestingly, the epiphyseal tubercle height and length were smaller and the metaphyseal fossa was larger in hips with cam-type FAI, suggesting varying inner bone surface morphology of the growth plate. The docking mechanism between the epiphyseal tubercle and the metaphyseal fossa is important for epiphyseal stability, particularly at early ages when the peripheral cupping is not fully developed. An underdeveloped tubercle and a large fossa could be associated with a reduction in stability, while excessive peripheral cupping growth would be a factor related to improved physeal stability. This is further supported by observed side-to-side differences in tubercle and fossa morphology in patients with unilateral FAI. Further longitudinal studies would be worthwhile to study the causality and compensatory mechanisms related to epiphyseal and metaphyseal bony morphology in pathogenesis cam-type FAI. Such information will lay the foundation for developing imaging biomarkers to predict the risk of FAI or to monitor its progress, which are critical in clinical care planning. LEVEL OF EVIDENCE: Level III, prognostic study.

What Is the Association Among Epiphyseal Rotation, Translation, and the Morphology of the Epiphysis and Metaphysis in Slipped Capital Femoral Epiphysis?

BACKGROUND: Contemporary studies have described the rotational mechanism in patients with slipped capital femoral epiphysis (SCFE). However, there have been limited patient imaging data and information to quantify the rotation. Determining whether the epiphysis is rotated or translated and measuring the epiphyseal displacement in all planes may facilitate planning for surgical reorientation of the epiphysis. QUESTIONS/PURPOSES: (1) How does epiphyseal rotation and translation differ among mild, moderate, and severe SCFE? (2) Is there a correlation between epiphyseal rotation and posterior or inferior translation in hips with SCFE? (3) Does epiphyseal rotation correlate with the size of the epiphyseal tubercle or the metaphyseal fossa or with epiphyseal cupping? METHODS: We identified 51 patients (55% boys [28 of 51]; mean age 13 ± 2 years) with stable SCFE who underwent preoperative CT of the pelvis before definitive treatment. Stable SCFE was selected because unstable SCFE would not allow for accurate assessment of rotation given the complete displacement of the femoral head in relation to the neck. The epiphysis and metaphysis were segmented and reconstructed in three-dimensions (3-D) for analysis in this retrospective study. One observer (a second-year orthopaedic resident) performed the image segmentation and measurements of epiphyseal rotation and translation relative to the metaphysis, epiphyseal tubercle, metaphyseal fossa, and the epiphysis extension onto the metaphysis defined as epiphyseal cupping. To assess the reliability of the measurements, a randomly selected subset of 15 hips was remeasured by the primary examiner and by the two experienced examiners independently. We used ANOVA to calculate the intraclass and interclass correlation coefficients (ICCs) for intraobserver and interobserver reliability of rotational and translational measurements. The ICC values for rotation were 0.91 (intraobserver) and 0.87 (interobserver) and the ICC values for translation were 0.92 (intraobserver) and 0.87 (intraobserver). After adjusting for age and sex, we compared the degree of rotation and translation among mild, moderate, and severe SCFE. Pearson correlation analysis was used to assess the associations between rotation and translation and between rotation and tubercle, fossa, and cupping measurements. RESULTS: Hips with severe SCFE had greater epiphyseal rotation than hips with mild SCFE (adjusted mean difference 21° [95% CI 11° to 31°]; p < 0.001) and hips with moderate SCFE (adjusted mean difference 13° [95% CI 3° to 23°]; p = 0.007). Epiphyseal rotation was positively correlated with posterior translation (r = 0.33 [95% CI 0.06 to 0.55]; p = 0.02) but not with inferior translation (r = 0.16 [95% CI -0.12 to 0.41]; p = 0.27). There was a positive correlation between rotation and metaphyseal fossa depth (r = 0.35 [95% CI 0.08 to 0.57]; p = 0.01), width (r = 0.41 [95% CI 0.15 to 0.61]; p = 0.003), and length (r = 0.56 [95% CI 0.38 to 0.75]; p < 0.001). CONCLUSION: This study supports a rotational mechanism for the pathogenesis of SCFE. Increased rotation is associated with more severe slips, posterior epiphyseal translation, and enlargement of the metaphyseal fossa. The rotational nature of the deformity, with the center of rotation at the epiphyseal tubercle, should be considered when planning in situ fixation and realignment surgery. Avoiding placing a screw through the epiphyseal tubercle-the pivot point of rotation- may increase the stability of the epiphysis. The realignment of the epiphysis through rotation rather than simple translation is recommended during the open subcapital realignment procedure. Enlargement of the metaphyseal fossa disrupts the interlocking mechanism with the tubercle and increases epiphyseal instability. Even in the setting of a stable SCFE, an increased fossa enlargement may indicate using two screws instead of one screw, given the severity of epiphyseal rotation and the risk of instability. Further biomechanical studies should investigate the number and position of in situ fixation screws in relation to the epiphyseal tubercle and metaphyseal fossa. LEVEL OF EVIDENCE: Level III, prognostic study.

MicroRNAs signatures, bioinformatics analysis of miRNAs, miRNA mimics and antagonists, and miRNA therapeutics in osteosarcoma.

MicroRNAs (miRNAs) involved in key signaling pathways and aggressive phenotypes of osteosarcoma (OS) was discussed, including PI3K/AKT/MTOR, MTOR AND RAF-1 signaling, tumor suppressor P53- linked miRNAs, NOTCH- related miRNAs, miRNA -15/16 cluster, apoptosis related miRNAs, invasion-metastasis-related miRNAs, and 14Q32-associated miRNAs cluster. Herrin, we discussed insights into the targeted therapies including miRNAs (i.e., tumor-suppressive miRNAs and oncomiRNAs). Using bioinformatics tools, the interaction network of all OS-associated miRNAs and their targets was also depicted.

What Is the Accuracy and Reliability of the Peritubercle Lucency Sign on Radiographs for Early Diagnosis of Slipped Capital Femoral Epiphysis Compared With MRI as the Gold Standard?

BACKGROUND: The diagnosis of slipped capital femoral epiphysis (SCFE) often is delayed. Although lack of clinical suspicion is the main cause of delayed diagnosis, typical radiographic changes may not be present during the initial phases of SCFE. The peritubercle lucency sign for follow-up of the contralateral hip in patients with unilateral SCFE may be beneficial in assisting the early diagnosis. However, the accuracy and reliability of this sign in patients with SCFE is unknown. QUESTIONS/PURPOSES: (1) What is the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the peritubercle lucency sign on radiographs for the early diagnosis of SCFE compared with MRI as the gold standard? (2) What are the interobserver and intraobserver reliabilities of the peritubercle lucency sign on radiographs? METHODS: Between 2000 and 2017, 71 patients underwent MRI for an evaluation of pre-slip or a minimally displaced SCFE. Sixty percent of hips (43 of 71) had confirmed SCFE or pre-slip based on the presence of hip pain and MRI changes, and these patients underwent in situ pinning. Three independent experienced observers reviewed MR images of the 71 hips and agreed on the presence of a juxtaphyseal bright-fluid signal suggesting bone marrow edema in these 43 hips with SCFE, and absence MRI changes in the remaining 28 hips. The same three experienced observers and two inexperienced observers, including a general radiologist and an orthopaedic surgery resident, blindly assessed the radiographs for the presence or absence of the peritubercle lucency sign, without information about the diagnosis. Diagnostic accuracy measures including sensitivity, specificity, PPV, and NPV were evaluated. Intraobserver and interobserver agreements were calculated using kappa statistics. RESULTS: The overall accuracy of the peritubercle lucency sign on radiographs was 94% (95% CI 91 to 96), sensitivity was 97% (95% CI 95 to 99), specificity was 89% (95% CI 90 to 96), PPV was 93% (95% CI 90 to 96), and NPV was 95% (95% CI 92 to 99). All accuracy parameters were greater than 85% for the five observers, regardless of experience level. Intraobserver agreement was perfect (kappa 1.0), and interobserver agreement was excellent for the peritubercle lucency sign on radiographs across the five observers (kappa 0.81 [95% CI 0.73 to 0.88]). The reliability was excellent for experienced observers (kappa 0.88 [95% CI 0.74 to 1.00]) and substantial for inexperienced observers (kappa 0.70 [95% CI 0.46 to 0.93]), although no difference was found with the numbers available (p = 0.18). CONCLUSIONS: The peritubercle lucency sign on radiographs is accurate and reliable for the early diagnosis of SCFE compared with MRI as the gold standard. Improving the early diagnosis of SCFE may be possible with increased awareness, high clinical suspicion, and a scrutinized evaluation of radiographs including an assessment of the peritubercle lucency sign. LEVEL OF EVIDENCE: Level III, diagnostic study.

Changes in Functional Meniscal Morphology During Skeletal Growth and Maturation.

Background: Little is known on how meniscal morphology develops during skeletal growth and maturation and its subsequent relationship with the corresponding bony anatomy. Hypotheses: (1) Meniscal dimensions and morphology would change by age during skeletal growth and maturation in different ways in boys compared with girls. (2) Morphological features of the medial and lateral menisci would correlate to medial and lateral femoral condyle curvatures. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Anatomic features of the medial and lateral menisci were measured on magnetic resonance imaging scans from 269 unique knees (age, 3-18 years; 51% female) with no prior history of injury, congenital or growth-related skeletal disorders, or bony deformities. Morphological shape-based measurements were normalized to tibial plateau width or determined as ratios of meniscal dimensions. The association between age and anatomy was analyzed with linear regression. Two-way analysis of variance with the Holm-Sídák post hoc method was used to compare anatomy between sexes in different age groups. Linear regression was used to evaluate the relationship between femoral condyle curvature radius and meniscal morphology in each compartment after adjusting for age and sex. Results: Meniscal length, width, horn distance, mean cross-sectional area (CSA), and mean height increased with age in both sexes (R2 > 0.1; P < .001). Age-related changes in meniscal morphology were seen in normalized length, width, horn distance, and mean height; width-to-length ratio; horn distance-to-length ratio (lateral meniscus only); normalized mean CSA (except lateral meniscus in girls); and mean tip angle (R2 > 0.04; P < .02). Sex-based differences were also found, with some morphological differences (normalized length and height) throughout development (P < .03) and size differences (length, width, and mean CSA) in later development (P < .01). After adjusting for age and sex, there were significant correlations between medial condyle curvature radius and normalized width, width-to-length ratio, horn distance, horn distance-to-length ratio, mean CSA, and mean height of the medial meniscus (P≤ .041) and between lateral condyle curvature radius and normalized length, mean height, and mean tip angle of the lateral meniscus (P≤ .004). Conclusion: Age-related changes in meniscal dimensions and morphology, most notably a nonuniform growth pattern in meniscal geometry, occurred during skeletal growth and maturation, with different trends in boys than in girls.

Hip Reconstruction In Situ with Screws and Cement (HiRISC) construct to treat large acetabular bone defects.

Aims: Large bone defects resulting from osteolysis, fractures, osteomyelitis, or metastases pose significant challenges in acetabular reconstruction for total hip arthroplasty. This study aimed to evaluate the survival and radiological outcomes of an acetabular reconstruction technique in patients at high risk of reconstruction failure (i.e. periprosthetic joint infection (PJI), poor bone stock, immunosuppressed patients), referred to as Hip Reconstruction In Situ with Screws and Cement (HiRISC). This involves a polyethylene liner embedded in cement-filled bone defects reinforced with screws and/or plates for enhanced fixation. Methods: A retrospective chart review of 59 consecutive acetabular reconstructions was performed by four surgeons in a single institution from 18 October 2018 to 5 January 2023. Cases were classified based on the Paprosky classification, excluding type 1 cases (n = 26) and including types 2 or 3 for analysis (n = 33). Radiological loosening was evaluated by an orthopaedic surgeon who was not the operating surgeon, by comparing the immediate postoperative radiographs with the ones at latest follow-up. Mean follow-up was 557 days (SD 441; 31 to 1,707). Results: Out of the 33 cases analyzed, six (18.2%) constructs required revision, with four revisions due to uncontrolled infection, one for dislocation, and one for aseptic loosening. Among the 27 non-revised constructs, only one showed wider radiolucencies compared to immediate postoperative radiographs, indicating potential loosening. Patients who underwent revision (n = 6) were significantly younger and had a higher BMI compared to those with non-revised constructs (p = 0.016 and p = 0.026, respectively). Sex, race, ethnicity, American Society of Anesthesiologists grade, infection status (patients with postoperative PJI diagnosis (septic) vs patients without such diagnosis (aseptic)), and mean follow-up did not significantly differ between revised and non-revised groups. Conclusion: The HiRISC technique may serve as a feasible short-term (about one to two years) alternative in patients with large acetabular defects, particularly in cases of PJI. Longer follow-up is necessary to establish the long-term survival of this technique.

Smaller epiphyseal tubercle in hips with slipped capital femoral epiphysis compared to the uninvolved contralateral hip.

Recent investigations suggest that physeal morphologic features have a major role in the capital femoral epiphysis stability and slipped capital femoral epiphysis (SCFE) pathology, with a smaller epiphyseal tubercle and larger peripheral cupping of the femoral epiphysis being present in hips with progressive SCFE compared to healthy controls. Yet, little is known on the causal versus remodeling nature of these associations. This study aimed to use preoperative magnetic resonance imaging (MRI) of patients with unilateral SCFE to perform a comparison of the morphology of the epiphyseal tubercle, metaphyseal fossa, and peripheral cupping in hips with SCFE versus the contralateral uninvolved hips. Preoperative MRIs from 22 unilateral SCFE patients were used to quantify the morphological features of the epiphyseal tubercle (height, width, and length), metaphyseal fossa (depth, width, and length), and peripheral cupping height in three dimension. The quantified anatomical features were compared between hips with SCFE and the contralateral uninvolved side across the whole cohort and within SCFE severity subgroups using paired t-test. We found significantly smaller epiphyseal tubercle heights (p < 0.001) across all severities of SCFE when compared to their uninvolved contralateral side. There was a marginally smaller metaphyseal fossa length (p = 0.05) in SCFE hips compared to their contralateral uninvolved hips, with mild SCFE hips specifically having smaller fossa and epiphyseal lengths (p < 0.05) than their contralateral uninvolved side. There were no side-to-side differences in any other features of the epiphyseal tubercle, metaphyseal fossa and peripheral cupping across all severities (p > 0.05). These findings suggest a potential causal role of epiphyseal tubercle in SCFE pathogenesis.

Femoral Head Osteonecrosis: Computed Tomography Not Needed to Identify Collapse When Using the Association Research Circulation Osseous Staging System.

Background: The 2019 Revised Association Research Circulation Osseous (ARCO) Staging Criteria for Osteonecrosis of the Femoral Head (ONFH) only requires plain radiographs and magnetic resonance imaging (MRI) to diagnose and stage ONFH; however, the effectiveness of the 2019 ARCO criteria in the absence of computed tomography (CT) scans has not been investigated. Therefore, the purpose of this study was to evaluate whether CT scanning is a necessary modality for diagnosing/staging ONFH using the ARCO staging system. More specifically, do CT scans help differentiate pre- and post-collapse lesions more than MRI scans? Methods: A study was conducted on 228 ONFH patients diagnosed between January 1, 2008, and December 31, 2018, at a single academic medical center. CT and MRI scans were reviewed by the senior author and other contributors. The ONFH classification was compared between the 2 scans to determine if CT scans were able to further differentiate staging of collapsed lesions vs MRI scans. Results: A diagnosis of ONFH was made by MRI first in 57% (129/228) while 21% (48/228) used MRI and CT simultaneously. Only 22% (51/228) of cases were diagnosed by CT scans first. There were no cases where collapse was found by a CT scan that were not diagnosed by standard x-rays and/or MRIs. Conclusions: CT scans are not a useful adjunct for diagnosing or treating ONFH and are not necessary if MRI is ordered when using the Revised ARCO Staging System for ONFH diagnosis.

Trabecular metal augments in severe malignancy-associated acetabular bone loss.

INTRODUCTION: Acetabular reconstruction is a challenging problem in orthopaedic oncology, especially in extended defects (Paprosky Type 3A and Type 3B). In revision total hip arthroplasty (THA), 1 option is trabecular metal (TM) augments with a porous metal acetabular component. This study evaluated the use of TM augments in periacetabular malignant bone disease. METHODS: 15 patients were identified from our institutional database from 2000 to 2020 with either Paprosky Type 3A or Type 3B acetabular bone loss due to periacetabular malignancies that underwent at least 1 complex THA reconstruction with TM augments. Postoperative complications were documented, and clinical and radiographic outcomes were analysed. Radiological loosening or revision of the acetabular component were defined as endpoints. RESULTS: There were 7 primary and 8 metastatic cancer patients. 5 were Type 3A and 10 were Type 3B defects after tumour resection. The average follow-up time was 23.8 (range 1.5-47) months. 1 patient required revision for acetabular component loosening after 7 months from the initial implantation. An additional 4 patients required surgical intervention for infection, they had stable TM augments at latest follow-up. CONCLUSION: TM augments with a porous metal acetabular component may be an alternative to the traditional cemented constructs.

Opioid over-prescription after total joint arthroplasty: Findings from patient reported opioid consumption journals.

We sought to determine postoperative opioid consumption for opioid-naïve patients undergoing total knee and hip arthroplasty (THA and TKA) procedures via an observational cohort study, consisting of 55 patients who underwent either primary unilateral TKA (n = 28) or THA (n = 27). Patients were provided with a journal to track daily consumption of pain medicine. Patients were prescribed an average of 67 opioid pills post-operatively; however, they consumed an average of 31 pills (214 morphine equivalent doses - MED). TKA patients received (p = 0.01) and consumed (p = 0.005) higher amounts of opioids. On average, patients ceased opioid usage at 14 days post-operatively.

Establishing a recommended duration of blood glucose monitoring in nondiabetic patients following orthopaedic surgery.

Previous studies have demonstrated that blood glucose (BG) levels should be monitored for at least 1 week after orthopaedic surgery in diabetic patients, but no study has determined how long nondiabetic patients should be monitored. As postoperative elevations in BG have deleterious effects, determining a duration for monitoring the BG of nondiabetic patients after major orthopaedic surgery is needed to detect hyperglycemic events, create comprehensive protocols for nondiabetic orthopaedic patients, and reduce adverse outcomes. A retrospective study was conducted including consecutive patients who underwent a major orthopaedic surgery at a community hospital. A BG level of 150 mg/dl was the cutoff used to define hyperglycemia according to our institutional guidelines. A χ2 , analysis of variance, and subgroup analysis were performed separately. Greater than 67% of nondiabetic patients experienced a high BG level (>150 mg/dl) after surgery. We found that nondiabetic patients reached their postoperative maximum BG level at 20 h, which was sooner compared to diabetic patients. We discovered more than 92% of nondiabetic patients reached a maximum BG levels within the first 72 h of hospitalization, while the BG levels after this period were found to be within normal limits in greater than 87% of cases. We propose that BG management be instituted in nondiabetics from the preoperative period to 72 h after surgery, including patients who are same-day discharges. There may not be a need to continue inpatient BG monitoring beyond the first 72 h for nondiabetic hospitalized patients with extended hospitalizations.

Plaster of Paris: Squeeze, But Not Too Hard!

Plaster of Paris (PoP) has been the predominant treatment option for most acute and chronic orthopedic conditions. Water immersion significantly decreases the PoP bandage strength. Moreover, concerns have been raised about the possibility of breaks in PoP splints and cast failures once solid. The current study was designed to account for the increase in weight associated with increased PoP layers. The authors hypothesized that by controlling for weight variation as layers increased, they could determine the number of layers of PoP bandage that truly results in optimal mechanical properties. They assessed whether adequate plaster weight control while increasing layers could improve the mechanical properties of the splint. [Orthopedics. 2022;45(1):e57-e61.].

Effect of the COVID-19 Pandemic on Rates of Ninety-Day Peri-Prosthetic Joint and Surgical Site Infections after Primary Total Joint Arthroplasty: A Multicenter, Retrospective Study.

Background: The impact of the coronavirus 2019 (COVID-19) pandemic on the rate of primary total joint arthroplasty (TJA) peri-prosthetic joint infection (PJI) and superficial surgical site infections (SSI) is currently unknown. The purpose of this multicenter study was to evaluate any changes in the rates of 90-day PJI or 30-day SSI, including trends in microbiology of the infections, during the COVID-19 pandemic compared to the three years prior. Patients and Methods: An Institutional Review Board-approved, multicenter, retrospective study was conducted with five participating academic institutions across two healthcare systems in the northeastern United States. Primary TJA patients from the years 2017-2019 were grouped as a pre-COVID-19 pandemic cohort and patients from the year 2020 were grouped as a COVID-19 pandemic cohort. Differences in patient demographics, PJI, SSI, and microbiology between the two cohorts were assessed. Results: A total of 14,844 TJAs in the pre-COVID-19 pandemic cohort and 5,453 TJAs in the COVID-19 pandemic cohort were evaluated. There were no substantial differences of the combined 90-day PJI and 30-day superficial SSI rates between the pre-COVID-19 pandemic cohort (0.35%) compared with the COVID-19 pandemic cohort (0.26%; p = 0.303). Conclusions: This study did not find any change in the rates of 90-day PJI or 30-day superficial SSI in patients undergoing primary TJA between a pre-COVID-19 pandemic and COVID-19 pandemic cohort. Larger national database studies may identify small but substantial differences in 90-day PJI and 30-day superficial SSI rates between these two time periods. Our data may support continued efforts to maintain high compliance with hand hygiene, use of personal protective equipment, and limited hospital visitation whenever possible.

One-Year Readmissions Following Total Joint Arthroplasty May Be Associated With Failure to Achieve the Minimal Clinically Important Difference of Patient-Reported Outcomes Measurement Information System Physical, Mental, and Physical-Short Form-10a.

The primary aims of our study were to determine if hospital readmissions within one year following primary total joint arthroplasty (TJA) and their relative timing influence patients' ability to achieve the two-year Patient-Reported Outcomes Measurement Information System (PROMIS) physical, PROMIS mental, and PROMIS Physical-Function-Short-Form-10a (SF-10a) minimal clinically important difference (MCID). This is a retrospective study conducted using data from a multi-institutional, arthroplasty registry. Only patients with paired patient-reported outcome measure (PROM) assessments (preoperatively and two years postoperatively) were included. Five separate readmission cohorts were formed: (1) any-cause readmission within one year, (2) any-cause readmission within 90 days, (3) non-index-surgery-related readmission within 90 days, (4) index-surgery-related readmission within one year, and (5) index-surgery-related readmission within 90 days. A propensity score match was used to match each of the patients to one of the 972 patients (1:1 basis) in the non-readmission group. The association between failure to achieve each of the three two-year MCIDs and Readmission status was analyzed using logistic regression. We found that all readmissions within one year and index-surgery-related readmissions within one year resulted in an increased risk of failure to achieve the two-year MCID across all three collected PROMs. Index surgery-related readmissions within 90 days (OR 3.24; 95% CI 1.05-11.05; p=0.048) sustained significantly different rates of two-year PROMIS physical MCID achievement compared to matched controls. Postoperative complications requiring readmission, particularly those related to the joint arthroplasty and those within 90 days of index surgery, significantly impact the ability to achieve the two-year MCID of PROMs.