CRP Predicts the Need to Escalate Care After Initial Debridement for Musculoskeletal Infection.

BACKGROUND: Musculoskeletal infections (MSKIs) are a major cause of morbidity in the pediatric population and account for nearly 1 in every 10 consultations with a pediatric orthopaedic provider at a tertiary care center. To prevent or deescalate the risk of adverse medical and musculoskeletal outcomes, timely medical intervention in the form of antibiotics and potential surgical debridement is required. While there have been numerous studies indicating the value of laboratory testing during the initial workup of a child with MSKI, few studies to date have examined the utility of longitudinal assessment of laboratory measures in the acute setting to monitor the efficacy of antibiotic therapy and/or surgical intervention. The purpose of this investigation was to retrospectively determine whether measuring changes in the inflammatory response could indicate the need for escalated care. Specifically, this study examined the hypothesis that serial measurements of C-reactive protein (CRP), immediately preoperatively and 2 days after surgical debridement, could predict the need for medical (change in antibiotics) or surgical (additional debridement) escalation. METHODS: Retrospective review of pediatric patients undergoing operative debridement for the treatment of MSKI between September 2009 and December 2015 from whom laboratory data (CRP) was obtained preoperatively and at postoperative day (POD) 2. Patient demographics, the need for escalated care, and patient outcomes were evaluated. RESULTS: Across 135 pediatric patients, preoperative CRP values >90 mg/L and a positive change in CRP at POD2 effectively predicted the need for escalation of care after initial surgical debridement (Area under the Receiver Operator Curve: 0.883). For each 10-unit increase in preoperative CRP or postoperative change in CRP, there was a 21% or 22% increased risk of needing escalated care, respectively. Stratification by preoperative CRP >90 mg/L and change in CRP postoperatively likewise correlated with increased rates of disseminated disease, percent tissue culture positivity, length of stay, and rate of adverse outcomes. CONCLUSIONS: This study demonstrates the utility of serial CRP to assess the need for escalated care in patients being treated for MSKI. As serial CRP measurements become standard of practice in the acute setting, future prospective studies are needed to optimize the timing of CRP reassessment during inpatient hospitalization to prognosticate patient outcomes, weighing both improvements of patient care and clinical burden. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

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.

Financial and Clinical Ramifications of Introducing a Novel Pediatric Enhanced Recovery After Surgery Pathway for Pediatric Complex Hip Reconstructive Surgery.

BACKGROUND: Enhanced recovery after surgery pathways confer significant perioperative benefits to patients and are currently well described for adult patients undergoing a variety of surgical procedures. Robust data to support enhanced recovery pathway use in children are relatively lacking in the medical literature, though clinical benefits are reported in targeted pediatric surgical populations. Surgery for complex hip pathology in the adolescent patient is painful, often requiring prolonged courses of opioid analgesia. Postoperative opioid-related side effects may lead to prolonged recovery periods and suboptimal postoperative physical function. Excessive opioid use in the perioperative period is also a major risk factor for the development of opioid misuse in adolescents. Perioperative opioid reduction strategies in this vulnerable population will help to mitigate this risk. METHODS: A total of 85 adolescents undergoing complex hip reconstructive surgery were enrolled into an enhanced recovery after surgery pathway (October 2015 to December 2018) and were compared with 110 patients undergoing similar procedures in previous years (March 2010 to September 2015). The primary outcome was total perioperative opioid consumption. Secondary outcomes included hospital length of stay, postoperative nausea, intraoperative blood loss, and other perioperative outcomes. Total cost of care and specific charge sectors were also assessed. Segmented regression was used to assess the effects of pathway implementation on outcomes, adjusting for potential confounders, including the preimplementation trend over time. RESULTS: Before pathway implementation, there was a significant downward trend over time in average perioperative opioid consumption (-0.10 mg total morphine equivalents/90 days; 95% confidence interval [CI], -0.20 to 0.00) and several secondary perioperative outcomes. However, there was no evidence that pathway implementation by itself significantly altered the prepathway trend in perioperative opioid consumption (ie, the preceding trend continued). For postanesthesia care unit time, the downward trend leveled off significantly (pre: -5.25 min/90 d; 95% CI, -6.13 to -4.36; post: 1.04 min/90 d; 95% CI, -0.47 to 2.56; Change: 6.29; 95% CI, 4.53-8.06). Clinical, laboratory, pharmacy, operating room, and total charges were significantly associated with pathway implementation. There was no evidence that pathway implementation significantly altered the prepathway trend in other secondary outcomes. CONCLUSIONS: The impacts of our pediatric enhanced recovery pathway for adolescents undergoing complex hip reconstruction are consistent with the ongoing improvement in perioperative metrics at our institution but are difficult to distinguish from the impacts of other initiatives and evolving practice patterns in a pragmatic setting. The ERAS pathway helped codify and organize this new pattern of care, promoting multidisciplinary evidence-based care patterns and sustaining positive preexisting trends in financial and clinical metrics.

The Heterogeneity of Pediatric Knee Infections: A Retrospective Analysis.

BACKGROUND: Musculoskeletal infection is a major cause of morbidity in the pediatric population. Despite the canonical teaching that an irritable joint and signs of infection likely represent an infected joint space, recent evidence in the pediatric hip has demonstrated that alternative diagnoses are equally or more likely and that combinations of pathologies are common. The knee is the second most commonly infected joint in children, yet there remains a paucity of available data regarding the epidemiology and workup of the infected pediatric knee. The authors hypothesize that there is heterogeneity of pathologies, including combinations of pathologies, that presents as a potentially infected knee in a child. The authors aim to show the utility of magnetic resonance imaging and epidemiologic and laboratory markers in the workup of these patients. METHODS: A retrospective review of all consults made to the pediatric orthopaedic surgery team at a single tertiary care center from September 2009 through December 2015 regarding a concern for potential knee infection was performed. Excluded from the study were patients with penetrating trauma, postoperative infection, open fracture, no C-reactive protein (CRP) within 24 hours of admission, sickle cell disease, an immunocompromised state, or chronic osteomyelitis. RESULTS: A total of 120 patients were analyzed in this study. There was marked variability in pathologies. Patients with isolated osteomyelitis or osteomyelitis+septic arthritis were older, had an increased admission CRP, were more likely to be infected with Staphylococcus aureus, required an increased duration of antibiotics, and had an increased incidence of musculoskeletal complications than patients with isolated septic arthritis. CONCLUSIONS: When considering a child with an irritable knee, a heterogeneity of potential underlying pathologies and combinations of pathologies are possible. Importantly, the age of the patient and CRP can guide a clinician when considering further workup. Older patients with a higher admission CRP value warrant an immediate magnetic resonance imaging, as they are likely to have osteomyelitis, which was associated with worse outcomes when compared with patients with isolated septic arthritis. LEVEL OF EVIDENCE: Level III-retrospective research study.

Surgical Margins in Musculoskeletal Sarcoma.

¼ Negative margin resection of musculoskeletal sarcomas is associated with reduced risk of local recurrence.¼ There is limited evidence to support an absolute margin width of soft tissue or bone that correlates with reduced risk of local recurrence.¼ Factors intrinsic to the tumor, including histologic subtype, grade, growth pattern and neurovascular involvement impact margin status and local recurrence, and should be considered when evaluating a patient's individual risk after positive margins.¼ Appropriate use of adjuvant therapy, critical analysis of preoperative advanced cross-sectional imaging, and the involvement of a multidisciplinary team are essential to obtain negative margins when resecting sarcomas.

Measures of Admission Immunocoagulopathy as an Indicator for In-Hospital Mortality in Patients with Necrotizing Fasciitis: A Retrospective Study.

Necrotizing fasciitis is a rapidly progressive infection with a high mortality rate. Pathogens evade the host containment and bactericidal mechanisms by hijacking the coagulation and inflammation signaling pathways, leading to their rapid dissemination, thrombosis, organ dysfunction, and death. This study examines the hypothesis that measures of immunocoagulopathy upon admission could aid in the identification of patients with necrotizing fasciitis at high risk for in-hospital mortality. Methods: Demographic data, infection characteristics, and laboratory values from 389 confirmed necrotizing fasciitis cases from a single institution were analyzed. A multivariable logistic regression model was built on admission immunocoagulopathy measures (absolute neutrophil, absolute lymphocyte, and platelet counts) and patient age to predict in-hospital mortality. Results: The overall in-hospital mortality rate was 19.8% for the 389 cases and 14.6% for the 261 cases with complete measures of immunocoagulopathy on admission. A multivariable logistic regression model indicated that platelet count was the most important predictor of mortality, followed by age and absolute neutrophil count. Greater age, higher neutrophil count, and lower platelet count led to significantly higher risk of mortality. The model discriminated well between survivors and non-survivors, with an overfitting-corrected C-index of 0.806. Conclusions: This study determined that measures of immunocoagulopathy and patient age at admission effectively prognosticated the in-hospital mortality risk of patients with necrotizing fasciitis. Given the accessibility of neutrophil-to-lymphocyte ratio and platelet count measurements determined from a simple complete blood-cell count with differential, future prospective studies examining the utility of these measures are warranted. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Head and Neck Necrotizing Fasciitis: Abbreviated SOFA Score Associated With Death and Infection Spread.

Objective: Describe features unique to head and neck (H&N) necrotizing fasciitis (NF) compared to other anatomic regions and specify a prognostic score associated with death and descending necrotizing mediastinitis (DNM). Study Design: Retrospective cohort. Setting: Tertiary care, level 1 trauma center. Methods: A single-institution database identified 399 confirmed cases of NF between 2006 and 2021, 33 of which involved the H&N. Patients with confirmed H&N NF were sorted into cohorts based on clinical outcomes, with the "poor" outcomes group defined by death and/or DNM. Results: Thirty-three patients with H&N NF were included. Compared to NF of other regions, patients with H&N NF had a significantly lower mortality rate (6.06% vs 20.8%, p = .041) and significantly lower rates of obesity (27.3% vs 63.7%, p < .001) and hypertension (42.4% vs 60.9%, p = .038). Within the H&N group, there were 2 deaths (6.06%) and 8 cases of DNM (24.2%). Diabetes was associated with poor outcomes (p = .047), as was an abbreviated sequential organ failure assessment score for necrotizing fasciitis (nfSOFA) of 2 or greater (p = .015). Conclusion: H&N NF is unique among other forms of NF, with a lower mortality rate and lower rates of obesity and hypertension in affected patients. Within the H&N cohort, worse outcomes were associated with diabetes as well as a nfSOFA score of 2 or greater. Timely surgical debridement alongside broad-spectrum antibiotics remains the mainstay of treatment for NF; however, this simple prognostic score may play a role during the early stages of care for patients with H&N NF.

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.

Quantitative Analysis of Growth Factors From Cancellous Bone Graft Collected With a Reamer-Irrigator-Aspirator System From Native Long Bones Versus Previously Reamed Long Bones.

OBJECTIVE: Collection of bone graft with the Reamer-Irrigator-Aspirator (RIA) system has become common practice across the field of orthopaedic surgery. While RIA bone graft is typically obtained from native long bones, grafting material can likewise be harvested from long bones that have previously undergone the placement and removal of an intramedullary nail, a process termed re-reamed RIA (RRR). The purpose of this study was to evaluate the total protein and growth factor concentrations present in native-RIA (NR) compared with RRR samples. METHODS: NR and RRR bone grafts were collected intraoperatively with the RIA system and processed to evaluate both the aqueous and the hard tissue components. Total protein concentration and specific growth factors were analyzed using standard bicinchoninic acid and multiplex assays, respectively. Analyte levels were then normalized to the total amount of protein detected. RESULTS: Total protein levels were comparable between NR and RRR samples for both the aqueous filtrate and the hard tissue samples. When normalized, while levels of bone morphogenic protein-2 and vascular endothelial growth factor were comparable in the hard tissue component, the aqueous filtrate from the RRR sample was found to have elevated levels of growth factors, with bone morphogenic protein-2 reaching statistical significance. CONCLUSIONS: This study demonstrates that ample protein is found within both NR and RRR samples, with comparable or elevated levels of osteogenic growth factors found within RRR samples. Future, larger, prospective studies will be required to evaluate the osteogenic potential and clinical efficacy of NR and RRR cancellous bone grafts to validate their equivalency.

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.