The Role of Routine Pathologic Assessment After Pediatric Osteochondroma Excision.

BACKGROUND: Osteochondromas are benign osseous lesions often excised for pain, growth abnormalities, and aesthetic concerns. While characteristic clinical and radiographic features leave little diagnostic ambiguity in most cases of osteochondroma, pathologic analysis to confirm the diagnosis and screen for malignancy is routinely performed following surgical excision. The purpose of this study was to determine the clinical and economic value of routine pathologic analysis after osteochondroma excision in a pediatric population. METHODS: A retrospective review of clinical records from 2 pediatric orthopaedic hospitals (St. Louis Children's Hospital and Shriner's Hospital for Children, St. Louis) identified 426 osteochondroma lesions surgically resected from 201 patients. Patients with solitary and multiple lesions were included. Clinical, radiographic, and surgical data were recorded for each resection surgery. Pathologic reports were evaluated. Costs incurred for routine pathologic assessment was also noted. RESULTS: Totally, 132 patients were treated with surgical resection of a solitary osteochondroma lesion, while an additional 291 lesions were resected from 69 patients with multiple lesions. Average age at the time of surgical resection was 13.0 years (2.1 to 17.9). The most common anatomic locations of excised lesions included the distal femur (110, 25.8%), proximal tibia/fibula (95, 22.3%), and distal radius/ulna (58, 13.6%). All resected specimens were sent for pathologic analysis. The average size of the resected lesions was 19.9 mm 3 (0.02 to 385.0 mm 3 ). In all cases, the histologic diagnosis confirmed benign osteochondroma. The total charges of pathologic analysis including processing and interpretation fees was ∼$755.00 for each lesion assessed, for a total cohort charge of $321,630. CONCLUSION: We propose that in most cases of pediatric osteochondroma excision procedures, postoperative histologic analysis is not strictly indicated as it rarely, if ever, alters diagnosis or management. We suggest using a "gross only" analysis in these cases. However, we do believe that with preoperative diagnostic ambiguity, or if patients present with concerning features such as rapidly expansile lesions or cortical destruction, have axial skeleton or pelvic involvement, or enlarged cartilaginous caps, full histologic evaluation of the excised lesions will continue to be prudent. LEVEL OF EVIDENCE: Level IV-case series.

PROMIS Physical Function and Pain Interference Scores Correlate with the Lower Extremity Toronto Extremity Salvage Score.

The Toronto Extremity Salvage Score (TESS) and the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) are both utilized to measure patient-reported outcomes in adults with musculoskeletal oncologic conditions. However, the relationship between them has not been studied. We sought to describe a link between Lower Extremity (LE) TESS and PROMIS Physical Function (PF) scores, as well as between LE TESS and Pain Interference (PI) scores, to develop a method for converting scores between TESS and PROMIS and to examine whether TESS and PROMIS captured differences in pain and function between clinically relevant subgroups in our population. Methods: Our study population consisted of 125 adult patients who underwent surgical treatment of a lower-extremity musculoskeletal tumor at a single sarcoma center between December 2015 and October 2018. The LE TESS questionnaire was administered to patients via paper and the PROMIS PF and PI were administered via iPad at a preoperative appointment. The relationship between LE TESS and PROMIS measures was analyzed with use of generalized linear modeling. Subgroup analyses were performed with a 2-tailed t test or 1-way analysis of variance. Results: PROMIS PF had a very strong positive correlation with LE TESS (r = 0.83) and was related through the following equation: PROMIS PF = 0.00294 × (LE TESS)2 + 22.6. PROMIS PI had a strong negative correlation with LE TESS (r = -0.77) and was related through the following equation: PROMIS PI = -0.00259 × (LE TESS)2 + 73.8. PROMIS PF and PI performed similarly to LE TESS across multiple patient subgroups and captured the expected differences between subgroups. Conclusions: LE TESS and PROMIS PF appeared to measure similar information in patients with an orthopaedic oncologic condition. Moreover, PROMIS PI scores were strongly correlated with functional disability as measured with the LE TESS. Understanding the relationship between TESS and PROMIS will allow the comparison and combination of data for both clinical and research purposes. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Preoperative and Postoperative Patient-Reported Outcome Measurement Information System Scores in Patients Treated for Benign Versus Malignant Soft Tissue Tumors.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) assesses multiple aspects of patient well-being but has not been thoroughly studied amongst orthopedic oncology patients. QUESTIONS/PURPOSES: How do preoperative/early postoperative PROMIS scores compare in patients with benign versus malignant soft tissue tumors (STTs) for (1) physical function, (2) pain interference, and (3) depression? Are the differences clinically relevant? What other patient/tumor factors impact PROMIS? METHODS: This retrospective cohort study included 314 STT patients who underwent resection of a benign (n = 187) or malignant (n = 127) STT over a period of 4.25 years at a single institution. PROMIS physical function, pain interference, and depression scores were collected preoperatively and at two and six weeks postoperatively. Scores for each time point were compared between groups and to preoperative baselines. Backward-stepwise linear mixed-effects models were produced to identify independent predictors of change in each PROMIS domain. The minimal clinically important difference (MCID) was 4 points. RESULTS: The malignant cohort, but not the benign cohort, demonstrated clinically relevant worsening of physical function postoperatively. Malignant diagnosis (△ = -4.4, p < 0.001) and lower extremity tumors (△ = -4.5, p < 0.001) were identified as clinically relevant, independent predictors of worse physical function at all time points. No predictors of clinically relevant changes in pain interference or depression scores, including malignancy, were identified. CONCLUSIONS: In STT patients, malignancy and lower extremity STT location are associated with clinically relevant worsening in physical function but do not significantly impact pain interference or depression in the early postoperative period. These findings may help establish the utility of PROMIS in an orthopedic oncology population.

Patients With Metastatic Disease Are at Highest Risk for Anxiety and Depression in an Orthopedic Oncology Patient Population.

PURPOSE: Patients with cancer are at risk for anxiety and depression; however, the patterns and predictors of symptoms in an orthopedic oncology population have not been studied. METHODS: We retrospectively reviewed Patient-Reported Outcomes Measurement Information System scores of all adult patients who underwent palliative surgery for metastatic cancer, resection of a sarcoma, or nononcologic total joint arthroplasty at a single institution from 2015 to 2020. Backward stepwise linear regression was used to determine risk factors for perioperative anxiety and depression. RESULTS: Postoperative anxiety and depression were more prevalent in patients with metastatic disease than localized cancer or nononcologic conditions (P < .001 and P < .001, respectively). Worse preoperative pain and function were associated with higher preoperative anxiety (ß = .321, P = .001; ß = -.236, P = .012, respectively) and depression (ß = .245, P = .009; ß = -.279, P = .003, respectively). Worse preoperative anxiety, preoperative depression, and postoperative pain were associated with higher postoperative anxiety (ß = .204, P = .012; ß = .260, P = .001; ß = .447, P < .001, respectively). Worse preoperative depression and postoperative pain also predicted higher postoperative depression (ß = .542, P < .001; ß = .325, P < .001, respectively). CONCLUSION: Anxiety and depression were most prevalent in patients with metastatic disease. Compared with total joint arthroplasty patients, patients with cancer less frequently experienced postoperative improvements in anxiety and depression. Worse preoperative pain and function were independently associated with greater preoperative anxiety and depression. Providers should maintain awareness of the relationship between mental and physical health to optimize outcomes.

Dedifferentiated chondrosarcoma with minimal or small dedifferentiated component.

Dedifferentiated chondrosarcoma (DDCS) is an aggressive bone sarcoma characterized by low-intermediate grade cartilage component with abrupt transition to a high-grade non-chondrosarcomatous component. Generally, the dedifferentiated (DD) component is large. However, rare cases have minimal (<1 cm) or small (1-2 cm) areas of DD. We describe the clinicopathologic features of such tumors and evaluate the prognostic significance of this finding compared to cases with large DD (>2 cm). Available slides were re-reviewed for assessment of histologic features. The medical record was reviewed for imaging studies and clinical characteristics. Thirty-five cases were included. Six patients had minimal DD, four had small DD and 25 had large DD. None of the minimal DD showed definitive imaging evidence of DD. Two minimal DD (33%) locally recurred and 2 (33%) developed distant metastases. None of the small DD cases showed definitive imaging evidence of DD. None of the small DD locally recurred and at least 1 (25%) developed distant metastases. There was no significant difference in age, gender, pelvic site, tumor size >8 cm, tumor necrosis or undifferentiated pleomorphic sarcoma-like morphology between minimal or small DD compared to large DD, though osteosarcomatous differentiation was significantly more common in large DD. There was no significant difference in overall survival between minimal or small DD compared to large DD (p = 0.81 and p = 0.17, respectively), or in progression-free survival (p = 0.47 and 0.29, respectively), or metastasis-free survival (p = 0.06 and 0.62, respectively). DDCS with minimal or small DD show similar demographic distribution, anatomic localization and histologic features to large DD. DD in these cases is unlikely to be detected on imaging. Furthermore, at least a subset of these tumors is extremely aggressive despite the limited extent of DD. This highlights the need for thorough gross and histologic examination and sampling.

Patterns of Extrapulmonary Metastases in Sarcoma Surveillance.

Soft tissue sarcomas (STS) most commonly metastasize to the lungs. Current surveillance guidelines variably recommend abdominal and pelvic imaging, but there is little evidence to support this. We sought to determine the proportion of initial pulmonary versus extrapulmonary metastases, the time to development of each, and factors to identify patients that would benefit from abdominopelvic surveillance. We retrospectively reviewed 382 patients who underwent surgical treatment for STS at a single institution. Of the 33% (126/382) of patients who developed metastases, 72% (90/126) were pulmonary, 22% (28/126) were extrapulmonary, and 6% (8/126) developed both simultaneously. Initial extrapulmonary metastases occurred later (log rank p = 0.049), with median 11 months (IQR, 5 to 19) until pulmonary disease and 22 months (IQR, 6 to 45) until extrapulmonary disease. Pulmonary metastases were more common in patients with high grade tumors (p = 0.0201) and larger tumors (p < 0.0001). Our multivariate analysis did not identify any factors associated with initial extrapulmonary metastases. A substantial minority of initial metastases were extrapulmonary; these occurred later and over a broader time range than initial pulmonary metastases. Moreover, extrapulmonary metastases are more difficult to predict than pulmonary metastases, adding to the challenge of creating targeted surveillance protocols.

Does Advanced Imaging Have a Role in Detecting Local Recurrence of Soft-tissue Sarcoma?

BACKGROUND: Early detection of soft-tissue sarcoma recurrences may decrease the morbidity of reoperation and improve oncologic outcomes. The benefit of imaging compared with clinical surveillance for detecting local recurrences remains controversial, as prior studies have varied in terms of inclusion criteria, factors analyzed, and outcomes reported. QUESTIONS/PURPOSES: (1) What proportion of local recurrences were detected by surveillance imaging compared with clinical signs and symptoms? (2) Were local recurrences detected by imaging smaller than those detected by clinical surveillance? (3) Were relevant tumor, patient, or operative characteristics associated with clinically occult local recurrence? METHODS: Over a 20-year period ending in 2018, we treated 545 patients for soft-tissue sarcoma. During that period, we recommended that patients receive a surgical excision as well as radiation therapy based on current clinical guidelines. Of those we treated, 9% (51 of 545) were excluded for having a low-grade liposarcoma, and 4% (21 of 545) were excluded for being metastatic at the time of presentation. Of the remaining patients, 22% (107 of 473) were lost to follow-up before 2 years but were not known to have died. There were a remaining 366 patients for analysis in this retrospective study of electronic medical records from a single center. Patients routinely underwent advanced imaging and clinical follow-up at intervals based on currently available guidelines for sarcoma surveillance. We recommended that patients with high-grade sarcomas be followed every 3 months until 2 years, then every 6 months until 3 years, then annually thereafter. In contrast, we recommended that patients with low-grade sarcomas be followed every 6 months until 2 years, then annually thereafter. In addition, patients were encouraged to return for evaluation if they noted a new mass or other symptoms. In general, patients with high-grade sarcomas received postoperative radiation therapy unless they underwent amputation, while intermediate- and low-grade sarcomas were radiated according to clinical concern for local recurrence, as determined by the multidisciplinary sarcoma team. Seventeen percent (61 of 366) of patients developed or presented with a local recurrence. Of the local recurrences detected by surveillance imaging, 17 were detected by MRI, three were detected by position emission tomography, and one was detected by CT scan. The proportion of local recurrences first identified by advanced imaging versus clinical detection (physical examination, self-detection, or symptomatic presentation) were compared. Logistic regression with a Wald chi-square test was performed to evaluate if tumor, patient, or operative characteristics are associated with clinical versus imaging detection of local recurrences. RESULTS: A higher proportion of local recurrences were detected by clinical signs and symptoms than by routine imaging (66% (40 of 61) versus 34% (21 of 61), binomial proportion 0.66 [95% CI 0.55 to 0.77]; p = 0.007). With the numbers available, there was no difference in the tumor size detected by clinical signs and symptoms compared with surveillance imaging. The median (interquartile range) largest tumor dimension was 3.9 cm (2.5 to 7.8) for clinical surveillance versus 4.5 cm (2.7 to 6.2) for imaging surveillance (p = 0.98). We were unable to identify any associated factors, alone or in combination, with detection by physical exam, including patient age, tumor size, tumor depth, tumor location, operative closure type, or radiation status. Characteristics such as larger tumors, more superficial tumors, low BMI, the absence of a flap reconstruction or radiation treatment, were not associated with a greater likelihood of detection by physical examination. CONCLUSIONS: We found that although a high proportion of local recurrences were detected by clinical signs and symptoms, approximately one-third were detected by imaging. Although not all patients may benefit equally from routine imaging, we were unable to identify any patient, tumor, or operative characteristics to define a subgroup of patients that are more or less likely benefit from this surveillance technique. These findings support current surveillance guidelines that recommend the use of advanced imaging; however, other factors may also warrant consideration. Futher insight could be gained by studying surveillance imaging in terms of optimal frequency, cost-effectiveness, and psychosocial implications for patients. LEVEL OF EVIDENCE: Level III, diagnostic study.

Immunoglobulins in the treatment of COVID-19 infection: Proceed with caution!

The COVID-19 pandemic is one of the greatest infectious challenges in recent history. Presently, few treatment options exist and the availability of effective vaccines is at least one year away. There is an urgent need to find currently available, effective therapies in the treatment of patients with COVID-19 infection. In this review, we compare and contrast the use of intravenous immunoglobulin and hyperimmune globulin in the treatment of COVID-19 infection.

RIG-I and TLR4 responses and adverse outcomes in pediatric influenza-related critical illness.

BACKGROUND: Decreased TNF-α production in whole blood after ex vivo LPS stimulation indicates suppression of the Toll-like receptor (TLR)4 pathway. This is associated with increased mortality in pediatric influenza critical illness. Whether antiviral immune signaling pathways are also suppressed in these patients is unclear. OBJECTIVES: We sought to evaluate suppression of the TLR4 and the antiviral retinoic acid-inducible gene-I (RIG-I) pathways with clinical outcomes in children with severe influenza infection. METHODS: In this 24-center, prospective, observational cohort study of children with confirmed influenza infection, blood was collected within 72 hours of intensive care unit admission. Ex vivo whole blood stimulations were performed with matched controls using the viral ligand polyinosinic-polycytidylic acid-low-molecular-weight/LyoVec and LPS to evaluate IFN-α and TNF-α production capacities (RIG-I and TLR4 pathways, respectively). RESULTS: Suppression of either IFN-α or TNF-α production capacity was associated with longer duration of mechanical ventilation and hospitalization, and increased organ dysfunction. Children with suppression of both RIG-I and TLR4 pathways (n = 33 of 103 [32%]) were more likely to have prolonged (≥7 days) multiple-organ dysfunction syndrome (30.3% vs 8.6%; P = .004) or prolonged hypoxemic respiratory failure (39.4% vs 11.4%; P = .001) compared with those with single- or no pathway suppression. CONCLUSIONS: Suppression of both RIG-I and TLR4 signaling pathways, essential for respective antiviral and antibacterial responses, is common in previously immunocompetent children with influenza-related critical illness and is associated with bacterial coinfection and adverse outcomes. Prospective testing of both pathways may aid in risk-stratification and in immune monitoring.

Patient-Reported Outcomes Measurement Information System physical function correlates with Toronto Extremity Salvage Score in an orthopaedic oncology population.

BACKGROUND: The National Institute of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) uses computerised-adaptive testing to reduce survey burden and improve sensitivity. PROMIS is being used across medical and surgical disciplines but has not been studied in orthopaedic oncology. QUESTIONS/PURPOSES: The aim of the study was to compare PROMIS measures with upper extremity (UE) and lower extremity (LE) Toronto Extremity Salvage Score (TESS) by assessing the following: (1) responder burden, (2) correlation between scores and (3) floor/ceiling effects. PATIENTS AND METHODS: This cross-sectional trial analysed all 97 adult patients treated surgically for a bone or soft tissue tumour at a tertiary institution between November 2015 and March 2016. TESS (UE or LE) and PROMIS (Physical Function, Pain Interference and Depression) surveys were administered preoperatively. Pearson correlations between each PROMIS domain and TESS were calculated, as were floor/ceiling effects of each outcome measure. RESULTS: (1) Completion of three PROMIS questionnaires required a mean total of 16.8 (+/- 5.8 standard deviation) questions, compared with 31 and 32 questions for the LE and UE TESS questionnaires, respectively. (2) The PROMIS Physical Function scores demonstrated a strong positive correlation with the LE TESS (r = 0.84; 95% confidence interval [CI], 0.72-0.91; p < 0.001) and moderate positive correlation with the UE TESS (r = 0.64; 95% CI, 0.34-0.83; p = 0.055). The PROMIS Depression scores demonstrated a weak negative correlation with both the LE TESS (r = -0.38; 95% CI, -0.61 to -0.10; p = 0.010) and with UE TESS (r = -0.38; 95% CI, -0.67 to -0.01; p = 0.055). The PROMIS Pain Interference scores demonstrated a strong negative correlation with the LE TESS (r = -0.71; 95% CI, -0.83 to -0.52; p < 0.001) and a moderate negative correlation with the UE TESS (r = -0.62; 95% CI, -0.81 to -0.30; p = 0.001). (3) The UE TESS had a range of scores from 16 to 100 with a 27% ceiling effect and no floor effect, and the LE TESS had a range from 10 to 98 with no floor or ceiling effect. There was no floor or ceiling effect for any PROMIS measures. CONCLUSIONS: In an orthopaedic oncology population, the PROMIS Physical Function and Pain Interference scores correlate with the TESS and have the benefit of reduced survey burden and ceiling effect. The PROMIS Depression scores may provide additional information regarding patient outcomes not captured by the TESS. LEVEL OF EVIDENCE: Level III. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Patient reported outcome measures asses patients' symptoms, function and health-related quality of life and are designed to capture more clinical information than can be gathered by objective medial testing alone. As reimbursements and the understanding of patient outcomes are becoming tied to performance on PROMIS measures, it is an important step to establish how PROMIS measures correlate and compare to traditional legacy measures.

How Effective Are Noninvasive Tests for Diagnosing Malignant Peripheral Nerve Sheath Tumors in Patients with Neurofibromatosis Type 1? Diagnosing MPNST in NF1 Patients.

BACKGROUND: Distinguishing between benign and malignant peripheral nerve sheath tumors (MPNSTs) in neurofibromatosis 1 (NF1) patients prior to excision can be challenging. How can MPNST be most accurately diagnosed using clinical symptoms, magnetic resonance imaging (MRI) findings (tumor size, depth, and necrosis), positron emission tomography (PET) measures (SUVpeak, SUVmax, SUVmax tumor/SUVmean liver, and qualitative scale), and combinations of the above? Methods. All NF1 patients who underwent PET imaging at our institution (January 1, 2007-December 31, 2016) were included. Medical records were reviewed for clinical findings; MR images and PET images were interpreted by two fellowship-trained musculoskeletal and nuclear medicine radiologists, respectively. Receiver operating characteristic (ROC) curves were created for each PET measurement; the area under the curve (AUC) and thresholds for diagnosing malignancy were calculated. Logistic regression determined significant predictors of malignancy. RESULTS: Our population of 41 patients contained 34 benign and 36 malignant tumors. Clinical findings did not reliably predict MPNST. Tumor depth below fascia was highly sensitive; larger tumors were more likely to be malignant but without a useful cutoff for diagnosis. Necrosis on MRI was highly accurate and was the only significant variable in the regression model. PET measures were highly accurate, with AUCs comparable and cutoff points consistent with prior studies. A diagnostic algorithm was created using MRI and PET findings. CONCLUSIONS: MRI and PET were more effective at diagnosing MPNST than clinical features. We created an algorithm for preoperative evaluation of peripheral nerve sheath tumors in NF1 patients, for which additional validation will be indicated.

Influence of Adrenal Venous Sampling on Management in Patients with Primary Aldosteronism Independent of Lateralization on Cross-Sectional Imaging.

BACKGROUND: Patients with primary aldosteronism undergo imaging of the adrenal glands after confirmation of the disease. Adrenal venous sampling (AVS) is a useful adjunct to imaging, and advocates believe that AVS should be performed before surgical management. Others argue that patients with unilateral lesions on imaging do not require AVS. Although AVS accuracy has been established, few studies have evaluated how AVS alters management. Our study aimed to determine how AVS affected management of these patients. STUDY DESIGN: Patient data were collected retrospectively from the electronic medical records at a single institution. Patients aged 18 years or older who underwent AVS with successful adrenal vein cannulation from 2007 to 2016 were included. The laterality of AVS was compared with laterality of preprocedural imaging for each patient. The management plan before AVS was determined by laterality on preprocedural imaging. The primary outcomes were management of primary aldosteronism, change in management compared with the plan before AVS, and antihypertensive medication use after therapy. RESULTS: Seventy-four patients had successful adrenal venous cannulation. Thirty-three (44.6%) patients had AVS lateralization that was concordant with preprocedural imaging. Forty-one (55.4%) patients had AVS lateralization that was non-concordant with preprocedural imaging. There was a change in management in 29 (39.2%) patients. CONCLUSIONS: Adrenal venous sampling can delineate the source of aldosterone hypersecretion, and often this is not concordant with cross-sectional imaging. We found that many patients avoided a potentially non-curative operation due to AVS. Adrenal venous sampling frequently alters the management of aldosteronomas and should be highly considered in patients before surgical intervention.

Does Patellar Tendon Repair With Gastrocnemius Flap Augmentation Effectively Restore Active Extension After Proximal Tibial Sarcoma Resection?

BACKGROUND: A rotational gastrocnemius flap is often used for soft tissue reconstruction after proximal tibia sarcoma resection. However, little is known about the frequency and severity of complications and the recovery of extensor function after this procedure. QUESTIONS/PURPOSES: After gastrocnemius flap reconstruction with split-thickness skin grafting (STSG) to augment the extensor mechanism repair after proximal tibial resection for sarcoma, we asked: (1) What ROM was achieved (including extensor lag and active flexion)? (2) How often did complications and reoperations occur and what caused them? METHODS: Between 1991 and 2014, one surgeon treated 26 patients with proximal tibial resections for primary bone sarcoma. Of these, 18 were reconstructed with the preferred approach: resecting the proximal tibia leaving the patellar tendon in continuity with the tibialis anterior fascia whenever possible (10), cementing a stemmed proximal tibial endoprosthesis, suturing the patellar tendon to the implant, rotating a medial (16) or lateral (two) gastrocnemius flap over the tendon and prosthesis to augment the repair, and covering the flap with STSG. Alternative methods were used when this was technically impossible (one patient), when there was no advantage to secondary soft tissue coverage (two patients), or when the limb could not be salvaged (five patients). Of the 18 treated with gastrocnemius flaps, two were lost to followup or died of disease before the 24-month minimum and excluded; the median followup of the remaining 16 was 6 years (mean, 9.9 years; range, 2.3-21.7 years); three patients died of disease, and four have not been seen within the last 5 years. We reviewed medical records for passive and active extension, maximum flexion achieved, and complications requiring reoperation. ROM in patients with successful limb salvage was graded as excellent (flexion ≥ 110° and no lag), good (flexion 90°-110° and lag ≤ 10°), fair (one function limited: either flexion < 90° or lag > 10°), or poor (both functions limited: flexion < 90° and lag > 10°). RESULTS: At latest followup, three patients had undergone amputation for deep infection. Of those remaining, median active flexion was 110° (mean, 104°; range, 60°-120°) and extensor lag was 0° (mean, 4°; range, 0°-10°). ROM was excellent in nine patients, good in three, fair in one, and poor in none. We observed 18 complications requiring reoperation in 12 patients, including deep infection (four), patellar tendon avulsion/attenuation (three), and flap necrosis (one). Survivorship free from revision or loss of the gastrocnemius flap was 74% (95% confidence interval [CI], 5.6-95.8) at 2, 5, and 10 years. Survivorship free from reoperation for any cause was 74% (95% CI, 52.0-96.0) at 2 years, 52% (95% CI, 25.8-77.8) at 5 years, and 35% (95% CI, 0-61.5) at 10 years using Kaplan-Meier analysis. CONCLUSIONS: Although most patients regained functional ROM including active extension, 12 required reoperation for complications including infection and early extensor mechanism failures. Despite the observed risks, we believe the gastrocnemius flap with STSG should be considered a suitable approach to provide active extension and soft tissue coverage given the paucity of good surgical options for extensor mechanism reconstruction in this challenging clinical setting. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Defective TLR9-driven STAT3 activation in B cells of patients with CVID.

B cell activation by Toll-like receptor 9 (TLR9) ligands is dependent on STAT3 and is important for optimal antibody responses to microbial antigens. B cells from patients with common variable immune deficiency (CVID) have impaired proliferation and differentiation in response to the TLR9 ligand CpG, despite normal levels of TLR9 expression. We demonstrate that CpG-driven STAT3 phosphorylation, but not activation of NFκB and p38, is selectively impaired in B cells from CVID patients. These results suggest that defective STAT3 activation contributes to the defective TLR9 and antibody response of B cells in CVID.

Primary Rosai-Dorfman disease of the femur.

We report a 19-year-old man with the rare occurrence of primary osseous Rosai-Dorfman disease (RDD). The patient presented with a painful, solitary, bone marrow-replacing lesion in the distal femur. A diagnosis of chronic osteomyelitis was initially made on tissue from a CT-guided needle biopsy of the lesion; however, the diagnosis of RDD was eventually made after histological and immunohistochemical analysis of material from a subsequent curettage. No lymphadenopathy or other sites of involvement were found on clinical evaluation and PET-CT. To our knowledge, this is the first report of solitary osseous RDD based on systemic staging with PET-CT. We review the clinical, imaging, and histological features of primary osseous RDD, including pitfalls in diagnosis.

Mechanical comparison of iliosacral reconstruction techniques after sarcoma resection.

BACKGROUND: Reconstruction of iliosacral defects following oncologic resection is a difficult clinical problem associated with a high incidence of failure. Technical approaches to this problem are heterogeneous and evidence supporting specific techniques is sparse. Maximizing construct stability may improve union rates and functional outcomes. The purpose of this study is to compare construct stiffness, load to failure, and mechanism of failure between two methods of iliosacral reconstruction in an ex-vivo model to determine if either is mechanically superior. METHODS: Eight third-generation composite pelves reconstructed with a plate-and-screw technique were tested against seven pelves reconstructed with a minimal spinal instrumentation technique using axial loading in a double-leg stance model. FINDINGS: The pelves from the plate group demonstrated higher stiffness in the direction of applied load (102.9 vs. 66.8N/mm; p=0.010) and endured a significantly larger maximum force (1416 vs. 1059N; p=0.015) than the rod group prior to failure. Subjectively, the rod-reconstructed pelves were noted to be rotationally unconstrained while pivoting around their single point-of fixation in each segment leading to earlier failure. INTERPRETATION: Plate-reconstruction was mechanically superior to spinal instrumentation in the manner performed in this study. More than one point of fixation in each segment should be achieved to minimize the risk of rotational deformation.

Hematopoietic stem cell transplantation outcomes for 11 patients with dedicator of cytokinesis 8 deficiency.

BACKGROUND: Dedicator of cytokinesis 8 (DOCK8) deficiency can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Reports of outcomes are still limited. OBJECTIVE: We sought to analyze the results of HSCT in patients with DOCK8 deficiency and report whether approaches resulting in mixed chimerism result in clinically relevant immune reconstitution. METHODS: We performed a retrospective chart review of 11 patients with DOCK8 deficiency and measured DOCK8 expression and cytokine production. RESULTS: Of 11 patients, 7 received HSCT from related and 4 from unrelated donors; 9 patients received busulfan-based conditioning regimens. Survival was excellent (10 [91%] of 11 patients alive), including a patient who had undergone liver transplantation. Patients showed significant improvements in the frequency and severity of infections. Although eczema resolved in all, food allergies and high IgE levels persisted in some patients. Lymphopenia, eosinophilia, low numbers of naive CD8(+) T cells and switched memory B cells, and TH1/TH2 cytokine imbalance improved in most patients. Although the 8 matched related or unrelated donor recipients had full donor chimerism, all 3 recipients of mismatched unrelated donor HSCT had high levels of donor T-cell chimerism and low B-cell and myeloid cell chimerism (0% to 46%). Almost all switched memory B cells were of donor origin. All patients, including those with mixed chimerism, mounted robust antibody responses to vaccination. CONCLUSION: Allogeneic HSCT ameliorated the infectious and atopic symptoms of patients with DOCK8 deficiency. In patients with mixed chimerism, selective advantage for donor-derived T cells and switched memory B cells promoted restoration of cellular and humoral immunity and protection against opportunistic infection.

Malignant Transformation of a Giant Cell Tumor of Bone Treated with Denosumab: A Case Report.

CASE: Giant cell tumor (GCT) of bone was first described almost 200 years ago, but the optimal treatment continues to evolve. We present a patient with a pelvic GCT who was treated with embolization, 20 months of denosumab therapy, and resection. Histologically, the tumor consisted of degenerated GCT, bone, and fibrous tissue. After 7 months, the patient was found to have osteosarcoma at the site of the initial lesion as well as pulmonary metastases. CONCLUSION: The apparent malignant transformation of a GCT of bone treated initially with denosumab indicates that close follow-up is warranted.

Pulmonary artery catheter-induced perforation treated with coil embolization.

The past 40 years have taught us much about the use of pulmonary artery catheters and their complications. Pulmonary artery rupture carries high morbidity and mortality, and therefore a high index of suspicion and timely management are key to the survival of patients who suffer from this rare complication. While surgical therapy has been considered the mainstay of treatment, endovascular therapy is feasible when surgery is not possible or desirable, as demonstrated in our patient. It is unknown which approach is optimal.

Imaging evaluation of treated benign bone tumours.

A number of benign bone tumours can be treated with curettage and packing with either bone cement or graft. It is essential that the radiologist be familiar with both the normal and abnormal post-operative imaging appearance of these treated tumours. Through the use of numerous imaging examples, we aim to provide a pictorial review of the expected post-operative appearance of benign bone tumours treated with curettage and packing, as well as the imaging features of recurrence, the most common potential complication.