Sequestration and Involucrum: Understanding Bone Necrosis and Revascularization in Pediatric Orthopedics.

Sequestration, a condition where a section of bone becomes necrotic due to a loss of vascularity or thrombosis, can be a challenging complication of osteomyelitis. This review explores the pathophysiology of sequestration, highlighting the role of the periosteum in forming involucrum and creeping substitution which facilitate revascularization and bone formation. The authors also discuss the induced membrane technique, a two-stage surgical procedure for cases of failed healing of sequestration. Future directions include the potential use of prophylactic anticoagulation and novel drugs targeting immunocoagulopathy, as well as the development of advanced imaging techniques and single-stage surgical procedures.

Navigating the Enigma of Pediatric Musculoskeletal Infections: A Race Against Time.

Musculoskeletal infection (MSKI) in children is a critical condition in pediatric orthopedics due to the potential for serious adverse outcomes, including multiorgan dysfunction syndrome, which can lead to death. The diagnosis and treatment of MSKI continue to evolve with advancements in infectious organisms, diagnostic technologies, and pharmacologic treatments. It is imperative for pediatric orthopedic surgeons and medical teams to remain up to date with the latest MSKI practices.

Symptom resolution following a repeat concussion within the same athlete.

INTRODUCTION: Repeat sport-related concussion (SRC) is anecdotally associated with prolonged recovery. Few studies have examined repeat concussion within the same athlete. We sought to explore differences in symptom burden and recovery outcomes in an individual athlete's initial and repeat SRC. METHODS: A retrospective within-subject cohort study of athletes aged 12-23 years diagnosed with two separate SRCs from 11/2017-10/2020 was conducted. Primary outcomes were initial symptom severity and time-to-symptom-resolution. Secondary outcomes included return-to-learn (RTL) and return-to-play (RTP) duration. RESULTS: Of 868 athletes seen, 47 athletes presented with repeat concussions. Median time between concussions was 244 days (IQR 136-395). Comparing initial to repeat concussion, no differences were observed in time-to-clinic (4.3 ± 7.3vs.3.7 ± 4.6 days, p = 0.56) or initial PCSS (26.2 ± 25.3 vs. 30.5 ± 24.1, p = 0.32). While a difference was observed in time-to-symptom resolution between initial/repeat concussion (21.2 ± 16.3 vs. 41.7 ± 86.0 days, p = 0.30), this did not reach statistical significance. No significant differences were observed in time-to-RTL (17.8 ± 60.6 vs. 6.0 ± 8.3 days, p = 0.26) and RTP (33.2 ± 44.1 vs. 29.4 ± 39.1 days, p = 0.75). Repeat concussion was not associated with symptom resolution on univariate (HR 1.64, 95% CI 0.96-2.78, p = 0.07) and multivariable (HR 0.85, 95% CI 0.49-1.46, p = 0.55) Cox regression. CONCLUSION: No significant differences in symptom duration and RTP/RTL were seen between initial/repeat concussion.

Sex Differences in Resource Allocation and Access to Care After Sport-Related Concussion.

CONTEXT: Following sport-related concussions (SRC), immediate access to a certified athletic trainer (ATC) is important to ensure proper treatment. However, resource allocation and coverage may differ between male/female youth sports. OBJECTIVE: We sought to compare resource allocation between male/female sports in the following areas: 1) rates of immediate on-field evaluation by an ATC at the time of injury, 2) time to general healthcare presentation, and 3) time to SRC clinic presentation. DESIGN: A retrospective cohort study. SETTING: Regional sports concussion center. PATIENTS: Athletes ages 14-19 who presented to a regional sports concussion center from 11/2017-04/2022 was conducted. MAIN OUTCOME MEASURES: The primary exposure of interest was sex (male/female). The primary outcome was immediate on-field evaluation by an ATC (yes/no). Secondary outcomes included time to general healthcare and SRC clinic presentation. Descriptive statistics, chisquared analyses, and linear regressions were performed. Covariates included age, history of prior concussions, and statistically significant demographics. RESULTS: A total of 832 patients with SRC were included (age 16.2±1.2, 66.5% male). Female athletes had lower rates of ADHD (X2=10.404, p=.001) and higher rates of anxiety/depression (X2=12.891, p< 0.001) compared to male athletes. Average time to presentation to general healthcare and SRC clinic did not differ between males/females, but ATC on-field evaluation occurred more in male (40.3%) than female (32.3%) athletes (X2=8.677, p=.013). Multivariable linear regression foun 24 d that ATC on-field evaluation was a significant predictor of time to general healthcare presentation (ß=-0.085, p=.015) but not SRC clinic presentation (ß=-0.055, p=.099). History of prior concussions was a significant predictor of time to initial healthcare contact (ß=0.083, p=.018). History of anxiety/depression (ß=0.136, p<.001) and initial evaluation by emergency department (ED)/urgent care (ß= 0.305, p<.001) were significant predictors of delayed time to SRC clinic presentation. CONCLUSIONS: Among 832 concussed youth athletes, female athletes were evaluated less frequently by an ATC immediately after injury. Furthermore, not being evaluated by an ATC on field was significantly associated with longer time to healthcare presentation. Future investigations should elucidate resource equity among male and female athletes.

Maintaining the balance: the critical role of plasmin activity in orthopedic surgery injury response.

The musculoskeletal system plays vital roles in the body, facilitating movement, protecting vital structures, and regulating hematopoiesis and mineral metabolism. Injuries to this system are common and can cause chronic pain, loss of range of motion, and disability. The acute phase response (APR) is a complex process necessary for surviving and repairing injured musculoskeletal tissue. To conceptualize the APR, it is useful to divide it into 2 distinct phases, survival and repair. During the survival-APR, a "damage matrix" primarily composed of fibrin, via thrombin activity, is produced to contain the zone of injury. Once containment is achieved, the APR transitions to the repair phase, where reparative inflammatory cells use plasmin to systematically remove the damage matrix and replace it with new permanent matrices produced by differentiated mesenchymal stem cells. The timing of thrombin and plasmin activation during their respective APR phases is crucial for appropriate regulation of the damage matrix. This review focuses on evidence indicating that inappropriate exuberant activation of plasmin during the survival-APR can result in an overactive APR, leading to an "immunocoagulopathy" that may cause "immunothrombosis" and death. Conversely, preclinical data suggest that too little plasmin activity during the repair-APR may contribute to failed tissue repair, such as a fracture nonunion, and chronic inflammatory degenerative diseases like osteoporosis. Future clinical studies are required to affirm these findings. Therefore, the temporal-spatial functions of plasmin in response to musculoskeletal injury and its pharmacologic manipulation are intriguing new targets for improving orthopedic care.

Surgical Fixation Method in Lower Extremity Intercalary Allograft Reconstruction After Oncologic Resection: A Comparison of Plates and Nails.

INTRODUCTION: Fixation in intercalary allograft reconstruction includes plates and intramedullary nails. The purpose of this study was to examine rates of nonunion, fracture, the overall need for revision surgery, and allograft survival based on the surgical fixation method in lower extremity intercalary allografts. METHODS: A retrospective chart review was performed on 51 patients with intercalary allograft reconstruction in the lower extremity. Fixation methods compared were intramedullary fixation with nails (IMN) and extramedullary fixation with plates (EMP). Complications compared were nonunion, fracture, and wound complications. The alpha was set at 0.05 for statistical analysis. RESULTS: Nonunion incidence at all allograft-to-native bone junction sites was 21% (IMN) and 25% (EMP) ( P = 0.8). Fracture incidence was 24% (IMN) and 32% (EMP) ( P = 0.75). Median fracture-free allograft survival was 7.9 years (IMN) and 3.2 years (EMP) ( P = 0.04). Infection was seen in 18% (IMN) and 12% (EMP) ( P = 0.7). The overall need for revision surgery was 59% (IMN) and 71% (EMP) ( P = 0.53). Allograft survival at the final follow-up was 82% (IMN) and 65% (EMP) ( P = 0.33). When the EMP group was subdivided into single plate (SP) and multiple plate (MP) groups and compared with the IMN groups, fracture rates were 24% (IMN), 8% (SP), and 48% (MP) ( P = 0.04). Rates of revision surgery were 59% (IMN), 46% (SP), and 86% (MP) ( P = 0.04). Allograft survival at the final follow-up was 88% (IMN), 92% (SP), and 52% (MP) ( P = 0.05). DISCUSSION: Median fracture-free allograft survival was notably longer for the IMN group than the EMP group; otherwise, there were no notable differences between the intramedullary and extramedullary groups. When the EMP group was subdivided into the SP and MP groups, patients with MPs had higher rates of fracture, higher rates of revision surgery, and lower overall allograft survival. LEVEL OF EVIDENCE: III, Therapeutic Study, Retrospective Comparative Study.

Predicting early versus late recovery from sport-related concussion using decision tree analysis.

OBJECTIVE: Accurately predicting early (≤ 14 days) versus typical (15-27 days) or delayed (≥ 28 days) recovery from sport-related concussion (SRC) may allow for improved resource utilization and precision in planning and carrying out rehabilitation. In this study, the authors sought to develop an algorithm that enables accurate differentiation of recovery periods and duration after SRC. The authors hypothesized that data regarding initial symptom burden as quantified by a Post-Concussion Symptom Scale (PCSS) score, time to presentation, and number of prior concussions would be the most useful for analyzing predictive factors for concussion recovery duration. METHODS: A retrospective case-control study was conducted to assess the primary outcome of days to clinical recovery following SRC in pediatric patients. Data from patients 12-18 years old presenting within 28 days of injury to an SRC clinic between November 11, 2017, and October 10, 2020, were analyzed. Patients with positive evidence of injury on head imaging or incomplete records were excluded. The primary outcome was duration of clinical recovery, grouped as early (≤ 14 days), typical (15-27 days), or delayed (≥ 28 days). Recovery was defined as follows: 1) symptom resolution or return to baseline, or 2) initiation of graduated return to play. CHAID (chi-square automatic interaction detection) analysis was used to optimize a decision tree based on 16 input factors, including age, sex, initial PCSS score, time to clinic presentation, number of prior concussions, and presence of defined symptom clusters. The cohort was randomized into training (70%) and test (30%) samples for algorithm validation. RESULTS: A total of 493 patients met the inclusion criteria (mean age 15.7 ± 1.5 years, 68.2% male, 70.0% White). The median time to presentation was 5 days (IQR 2-10 days). Most patients (52.3%) recovered within 14 days of injury, 21.5% recovered within 15-27 days, and 26.2% had a recovery period of 28 days or longer. The variables most predictive of recovery were initial PCSS score (cutoffs ≤ 6, 7-28, or ≥ 29), time to presentation (≤ 7 vs > 7 days), or prior concussions (0 vs ≥ 1). The model accurately discriminated between early versus typical or delayed recovery duration groupings (area under the curve 0.80, Youden index 0.44), and correctly classified > 90% of patients who recovered early. CONCLUSIONS: This novel three-factor predictive tool enabled accurate discrimination of early versus typical or delayed SRC recovery to better allocate resources, counsel patients, and make timely referrals.

Investigation of Factors Contributing to Racial Differences in Sport-Related Concussion Outcomes.

OBJECTIVE: Following sport-related concussion (SRC), early studies have demonstrated racial differences in time to clinical recovery; however, these differences have not been fully explained. We sought to further explore these associations by considering possible mediating/moderating factors. METHODS: Data from patients aged 12-18 years diagnosed with SRC from November 2017 to October 2020 were analyzed. Those missing key data, lost to follow-up, or missing race were excluded. The exposure of interest was race, dichotomized as Black/White. The primary outcome was time to clinical recovery (days from injury until the patient was either deemed recovered by an SRC provider or symptom score returned to baseline or zero.) RESULTS: A total of 389 (82%) White and 87 (18%) Black athletes with SRC were included. Black athletes more frequently reported no SRC history (83% vs. 67%, P = 0.006) and lower symptom burden at presentation (median total Post-Concussion Symptom Scale 11 vs. 23, P < 0.001) than White athletes. Black athletes achieved earlier clinical recovery (hazard ratio [HR] = 1.35, 95% CI 1.03-1.77, P = 0.030), which remained significant (HR = 1.32, 95% CI 1.002-1.73, P = 0.048) after adjusting for confounders associated with recovery but not race. A third model adding the initial Post-Concussion Symptom Scale score nullified the association between race/recovery (HR = 1.12, 95% CI 0.85-1.48, P = 0.410). Adding prior concussion history further reduced the association between race/recovery (HR = 1.01, 95% CI 0.77-1.34, P = 0.925). CONCLUSIONS: Overall, Black athletes initially presented with fewer concussion symptoms than White athletes, despite no difference in time to clinic. Black athletes achieved earlier clinical recovery following SRC, a difference explained by differences in initial symptom burden and self-reported concussion history. These crucial differences may stem from cultural/psychologic/organic factors.

Is the Number of National Database Research Studies in Musculoskeletal Sarcoma Increasing, and Are These Studies Reliable?

BACKGROUND: Large national databases have become a common source of information on patterns of cancer care in the United States, particularly for low-incidence diseases such as sarcoma. Although aggregating information from many hospitals can achieve statistical power, this may come at a cost when complex variables must be abstracted from the medical record. There is a current lack of understanding of the frequency of use of the Surveillance, Epidemiology, and End Results (SEER) database and the National Cancer Database (NCDB) over the last two decades in musculoskeletal sarcoma research and whether their use tends to produce papers with conflicting findings. QUESTIONS/PURPOSES: (1) Is the number of published studies using the SEER and NCDB databases in musculoskeletal sarcoma research increasing over time? (2) What are the author, journal, and content characteristics of these studies? (3) Do studies using the SEER and the NCDB databases for similar diagnoses and study questions report concordant or discordant key findings? (4) Are the administrative data reported by our institution to the SEER and the NCDB databases concordant with the data in our longitudinally maintained, physician-run orthopaedic oncology dataset? METHODS: To answer our first three questions, PubMed was searched from 2001 through 2020 for all studies using the SEER or the NCDB databases to evaluate sarcoma. Studies were excluded from the review if they did not use these databases or studied anatomic locations other than the extremities, nonretroperitoneal pelvis, trunk, chest wall, or spine. To answer our first question, the number of SEER and NCDB studies were counted by year. The publication rate over the 20-year span was assessed with simple linear regression modeling. The difference in the mean number of studies between 5-year intervals (2001-2005, 2006-2010, 2011-2015, 2016-2020) was also assessed with Student t-tests. To answer our second question, we recorded and summarized descriptive data regarding author, journal, and content for these studies. To answer our third question, we grouped all studies by diagnosis, and then identified studies that shared the same diagnosis and a similar major study question with at least one other study. We then categorized study questions (and their associated studies) as having concordant findings, discordant findings, or mixed findings. Proportions of studies with concordant, discordant, or mixed findings were compared. To answer our fourth question, a coding audit was performed assessing the concordance of nationally reported administrative data from our institution with data from our longitudinally maintained, physician-run orthopaedic oncology dataset in a series of patients during the past 3 years. Our orthopaedic oncology dataset is maintained on a weekly basis by the senior author who manually records data directly from the medical record and sarcoma tumor board consensus notes; this dataset served as the gold standard for data comparison. We compared date of birth, surgery date, margin status, tumor size, clinical stage, and adjuvant treatment. RESULTS: The number of musculoskeletal sarcoma studies using the SEER and the NCDB databases has steadily increased over time in a linear regression model (ß = 2.51; p < 0.001). The mean number of studies per year more than tripled during 2016-2020 compared with 2011-2015 (39 versus 13 studies; mean difference 26 ± 11; p = 0.03). Of the 299 studies in total, 56% (168 of 299) have been published since 2018. Nineteen institutions published more than five studies, and the most studies from one institution was 13. Orthopaedic surgeons authored 35% (104 of 299) of studies, and medical oncology journals published 44% (130 of 299). Of the 94 studies (31% of total [94 of 299]) that shared a major study question with at least one other study, 35% (33 of 94) reported discordant key findings, 29% (27 of 94) reported mixed key findings, and 44% (41 of 94) reported concordant key findings. Both concordant and discordant groups included papers on prognostic factors, demographic factors, and treatment strategies. When we compared nationally reported administrative data from our institution with our orthopaedic oncology dataset, we found clinically important discrepancies in adjuvant treatment (19% [15 of 77]), tumor size (21% [16 of 77]), surgery date (23% [18 of 77]), surgical margins (38% [29 of 77]), and clinical stage (77% [59 of 77]). CONCLUSION: Appropriate use of databases in musculoskeletal cancer research is essential to promote clear interpretation of findings, as almost two-thirds of studies we evaluated that asked similar study questions produced discordant or mixed key findings. Readers should be mindful of the differences in what each database seeks to convey because asking the same questions of different databases may result in different answers depending on what information each database captures. Likewise, differences in how studies determine which patients to include or exclude, how they handle missing data, and what they choose to emphasize may result in different messages getting drawn from large-database studies. Still, given the rarity and heterogeneity of sarcomas, these databases remain particularly useful in musculoskeletal cancer research for nationwide incidence estimations, risk factor/prognostic factor assessment, patient demographic and hospital-level variable assessment, patterns of care over time, and hypothesis generation for future prospective studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

Adjuvant Radiation after Primary Resection of Atypical Lipomatous Tumors of the Extremity Reduces Local Recurrence but Increases Complications: A Multicenter Evaluation.

Background: Radiation after resection of an atypical lipomatous tumor (ALT) is controversial. This study evaluates local control and complications after the first resection of ALTs of the extremity with or without adjuvant radiation. Methods: A dual institution, retrospective review of patients treated from 1995 to 2020 with first-time resection of an ALT in the extremity was performed. In total, 102 patients underwent adjuvant radiation (XRT group) and 68 patients were treated with surgery alone (no-XRT group). The median follow-up time was 4.6 years (interquartile range (IQR) 2.0-7.3 years). The median radiation dose was 60 Gy (IQR 55-66 Gy). Univariable and multivariable analyses evaluated the association of patient, tumor, and treatment variables with recurrence and complications. Kaplan-Meier analysis evaluated local recurrence-free survival (LRFS) and time to complication. Results: The overall incidence of local recurrence was 1% (1/102) in the XRT group and 24% (16/68) in the no-XRT group (p < 0.001). The median time-to-recurrence was 8.2 years (IQR 6.5-10.5 years). In the XRT and the no-XRT groups, 5-yr LRFS was 98% and 92% (p=0.21) and 10-yr LRFS was 98% and 41% (p < 0.001), respectively. The absence of radiation (HR = 23.63, 95% CI (3.09-180.48); p < 0.001) and R2 surgical resection margins (HR = 11.04, 95% CI (2.07-59.03); p < 0.001) incurred a 23-fold and 11-fold increased risk of local recurrence, respectively, while tumor size, depth, location, and neurovascular involvement were not found to be independent predictors of recurrence. The complication rate was 37% (38/102) in the XRT group and 10% (7/68) in the no-XRT group (p < 0.001). Eight patients (8/102, 8%) required surgical management for complication in the XRT group compared with two patients (2/68, 3%) in the no-XRT group (p=0.10). Higher radiation dose had a modest correlation with increased severity of complication (ρ=0.24; p=0.02). Conclusions: Adjuvant radiation after first-time resection of an ALT of the extremity was associated with a significantly reduced risk of local recurrence but a three-fold increase in complication rate. These data support a 10-year follow-up for these patients and inform a notable clinical trade-off if considering adjuvant radiation for this tumor with recurrent potential.

Use of acute cognitive symptom cluster to predict return-to-learn duration following a sport-related concussion.

OBJECTIVE: Adolescents sustaining sport-related concussion often experience difficulties with the return-to-learn (RTL) process. Whereas the initial symptom burden has predicted prolonged RTL, no studies have established a relationship between acute cognitive symptoms and RTL duration. The authors sought to evaluate the relationship between initial cognitive symptoms and RTL duration. METHODS: A retrospective single-institution cohort study of adolescent athletes aged 12-23 years who were evaluated within 5 days of a diagnosed sport-related concussion between November 2017 and October 2020 was conducted. Athletes missing cognitive symptom ratings and RTL data were excluded. The primary exposure variable was the Cognitive Symptom Ratio (CSR), defined as total cognitive symptom cluster score divided by total Post-Concussion Symptom Scale (PCSS) score from the initial clinic visit. Primary and secondary outcomes were time to RTL and total length of care, respectively. Multivariable Cox proportional hazards modeling was used to assess the effect of CSR on RTL duration. RESULTS: Of 653 athletes evaluated within 5 days of injury, 346 patients were included in the final cohort. Athletes reported a median initial PCSS score of 21 (interquartile range [IQR] 6-37) and a median cognitive symptom score of 4 (IQR 0-9). Most patients endorsed some degree of difficulty concentrating (n = 212, 61.3%). The median CSR was 0.18 (IQR 0.00-0.27). On multivariable regression analysis, a higher CSR was associated with prolonged RTL duration (HR 0.30, 95% CI 0.13-0.69, p = 0.004). When initial PCSS score was added to the model, the previously significant association between CSR and RTL was no longer significant (HR 0.67, 95% CI 0.29-1.59, p = 0.367). When dichotomized based on frequency distribution, a higher proportion of patients with low CSR achieved RTL by 7 days postinjury (82.2% vs 69.9%, p = 0.007), a difference not seen at 14 days (92.2% vs 87.3%, p = 0.133). CONCLUSIONS: An acute ratio of cognitive symptoms may predict patients at increased risk for prolonged RTL and those with normal PCSS scores who may experience difficulties once resuming school activities.