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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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

To understand the transmissibility and spread of infectious diseases, epidemiologists turn to estimates of the instantaneous reproduction number. While many estimation approaches exist, their utility may be limited. Challenges of surveillance data collection, model assumptions that are unverifiable with data alone, and computationally inefficient frameworks are critical limitations for many existing approaches. We propose a discrete spline-based approach that solves a convex optimization problem-Poisson trend filtering-using the proximal Newton method. It produces a locally adaptive estimator for instantaneous reproduction number estimation with heterogeneous smoothness. Our methodology remains accurate even under some process misspecifications and is computationally efficient, even for large-scale data. The implementation is easily accessible in a lightweight R package rtestim., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble is the 2 nd most accurate model measured by WIS in 2021-22 and the 5 th most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Human learning varies greatly among individuals and is related to the microstructure of major white matter tracts in several learning domains, yet the impact of the existing microstructure of white matter tracts on future learning outcomes remains unclear. We employed a machine-learning model selection framework to evaluate whether existing microstructure might predict individual differences in learning a sensorimotor task, and further, if the mapping between tract microstructure and learning was selective for learning outcomes. We used diffusion tractography to measure the mean fractional anisotropy (FA) of white matter tracts in 60 adult participants who then practiced drawing a set of 40 unfamiliar symbols repeatedly using a digital writing tablet. We measured drawing learning as the slope of draw duration over the practice session and measured visual recognition learning for the symbols using an old/new 2-AFC task. Results demonstrated that tract microstructure selectively predicted learning outcomes, with left hemisphere pArc and SLF3 tracts predicting drawing learning and the left hemisphere MDLFspl predicting visual recognition learning. These results were replicated using repeat, held-out data and supported with complementary analyses. Results suggest that individual differences in the microstructure of human white matter tracts may be selectively related to future learning outcomes., (© 2024. The Author(s).)

Forecasting methodologies have always attracted a lot of attention and have become an especially hot topic since the beginning of the COVID-19 pandemic. In this paper we consider the problem of multi-period forecasting that aims to predict several horizons at once. We propose a novel approach that forces the prediction to be "smooth" across horizons and apply it to two tasks: point estimation via regression and interval prediction via quantile regression. This methodology was developed for real-time distributed COVID-19 forecasting. We illustrate the proposed technique with the CovidCast dataset as well as a small simulation example., Competing Interests: Conflict of Interest: None declared.

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., (Copyright © 2023 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Functional MRI (fMRI) data may be contaminated by artifacts arising from a myriad of sources, including subject head motion, respiration, heartbeat, scanner drift, and thermal noise. These artifacts cause deviations from common distributional assumptions, introduce spatial and temporal outliers, and reduce the signal-to-noise ratio of the data-all of which can have negative consequences for the accuracy and power of downstream statistical analysis. Scrubbing is a technique for excluding fMRI volumes thought to be contaminated by artifacts and generally comes in two flavors. Motion scrubbing based on subject head motion-derived measures is popular but suffers from a number of drawbacks, among them the need to choose a threshold, a lack of generalizability to multiband acquisitions, and high rates of censoring of individual volumes and entire subjects. Alternatively, data-driven scrubbing methods like DVARS are based on observed noise in the processed fMRI timeseries and may avoid some of these issues. Here we propose "projection scrubbing", a novel data-driven scrubbing method based on a statistical outlier detection framework and strategic dimension reduction, including independent component analysis (ICA), to isolate artifactual variation. We undertake a comprehensive comparison of motion scrubbing with data-driven projection scrubbing and DVARS. We argue that an appropriate metric for the success of scrubbing is maximal data retention subject to reasonable performance on typical benchmarks such as the validity, reliability, and identifiability of functional connectivity. We find that stringent motion scrubbing yields worsened validity, worsened reliability, and produced small improvements to fingerprinting. Meanwhile, data-driven scrubbing methods tend to yield greater improvements to fingerprinting while not generally worsening validity or reliability. Importantly, however, data-driven scrubbing excludes a fraction of the number of volumes or entire sessions compared to motion scrubbing. The ability of data-driven fMRI scrubbing to improve data retention without negatively impacting the quality of downstream analysis has major implications for sample sizes in population neuroscience research., (Copyright © 2023. Published by Elsevier Inc.)

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., (© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Motivation: Methods for the global measurement of transcript abundance such as microarrays and RNA-Seq generate datasets in which the number of measured features far exceeds the number of observations. Extracting biologically meaningful and experimentally tractable insights from such data therefore requires high-dimensional prediction. Existing sparse linear approaches to this challenge have been stunningly successful, but some important issues remain. These methods can fail to select the correct features, predict poorly relative to non-sparse alternatives or ignore any unknown grouping structures for the features., Results: We propose a method called SuffPCR that yields improved predictions in high-dimensional tasks including regression and classification, especially in the typical context of omics with correlated features. SuffPCR first estimates sparse principal components and then estimates a linear model on the recovered subspace. Because the estimated subspace is sparse in the features, the resulting predictions will depend on only a small subset of genes. SuffPCR works well on a variety of simulated and experimental transcriptomic data, performing nearly optimally when the model assumptions are satisfied. We also demonstrate near-optimal theoretical guarantees., Availability and Implementation: Code and raw data are freely available at https://github.com/dajmcdon/suffpcr. Package documentation may be viewed at https://dajmcdon.github.io/suffpcr., Contact: daniel@stat.ubc.ca., Supplementary Information: Supplementary data are available at Bioinformatics Advances online., (© The Author(s) 2022. Published by Oxford University Press.)

The COVID-19 pandemic presented enormous data challenges in the United States. Policy makers, epidemiological modelers, and health researchers all require up-to-date data on the pandemic and relevant public behavior, ideally at fine spatial and temporal resolution. The COVIDcast API is our attempt to fill this need: Operational since April 2020, it provides open access to both traditional public health surveillance signals (cases, deaths, and hospitalizations) and many auxiliary indicators of COVID-19 activity, such as signals extracted from deidentified medical claims data, massive online surveys, cell phone mobility data, and internet search trends. These are available at a fine geographic resolution (mostly at the county level) and are updated daily. The COVIDcast API also tracks all revisions to historical data, allowing modelers to account for the frequent revisions and backfill that are common for many public health data sources. All of the data are available in a common format through the API and accompanying R and Python software packages. This paper describes the data sources and signals, and provides examples demonstrating that the auxiliary signals in the COVIDcast API present information relevant to tracking COVID activity, augmenting traditional public health reporting and empowering research and decision-making., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Short-term forecasts of traditional streams from public health reporting (such as cases, hospitalizations, and deaths) are a key input to public health decision-making during a pandemic. Since early 2020, our research group has worked with data partners to collect, curate, and make publicly available numerous real-time COVID-19 indicators, providing multiple views of pandemic activity in the United States. This paper studies the utility of five such indicators-derived from deidentified medical insurance claims, self-reported symptoms from online surveys, and COVID-related Google search activity-from a forecasting perspective. For each indicator, we ask whether its inclusion in an autoregressive (AR) model leads to improved predictive accuracy relative to the same model excluding it. Such an AR model, without external features, is already competitive with many top COVID-19 forecasting models in use today. Our analysis reveals that 1) inclusion of each of these five indicators improves on the overall predictive accuracy of the AR model; 2) predictive gains are in general most pronounced during times in which COVID cases are trending in "flat" or "down" directions; and 3) one indicator, based on Google searches, seems to be particularly helpful during "up" trends., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Heterogeneity in transcription initiation has important consequences for transcript stability and translation, and shifts in transcription start site (TSS) usage are prevalent in various developmental, metabolic, and disease contexts. Accordingly, numerous methods for global TSS profiling have been developed, including most recently Survey of TRanscription Initiation at Promoter Elements with high-throughput sequencing (STRIPE-seq), a method to profile transcription start sites (TSSs) on a genome-wide scale with significant cost and time savings compared to previous methods. In anticipation of more widespread adoption of STRIPE-seq and related methods for construction of promoter atlases and studies of differential gene expression, we built TSRexploreR, an R package for end-to-end analysis of TSS mapping data. TSRexploreR provides functions for TSS and transcription start region (TSR) detection, normalization, correlation, visualization, and differential TSS/TSR analyses. TSRexploreR is highly interoperable, accepting the data structures of TSS and TSR sets generated by several existing tools for processing and alignment of TSS mapping data, such as CAGEr for Cap Analysis of Gene Expression (CAGE) data. Lastly, TSRexploreR implements a novel approach for the detection of shifts in TSS distribution., (© The Author(s) 2021. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Background: Limited data exist regarding the prevalence of substance use disorders or utilization of mental health care during the COVID-19 pandemic. Our study aims to specifically identify trends in the utilization of behavioral health units (BHU) in those with substance use disorders (SUD)., Methods: Patient electronic health records (EHR) were analyzed from fourteen hospitals principally located in the US mid-Atlantic region. To compare SUD admissions before and after COVID-19 quarantine time periods, patient data from BHUs were collected from two time-periods: February 1st, 2019 to May 31st, 2019, and February 1st, 2020 to May 31st, 2020., Results: The number of SUD admissions to BHUs did not change from 2019 to 2020 but there was a statistically significant difference in the proportion of SUD patients admitted to BHUs (χ 2 = 83.47, p < .001, V = 0.06). We also detected a significant difference in the proportion of SUD severity between 2019 and 2020 with a small but significant overall decrease in the proportion of moderate/severe cases (χ 2 = 5.70, p < .001, V = 0.05) in SUD patients., Conclusion: Our data suggest that even during the times of a global pandemic when there is a decline in health care utilization in other settings, the need for inpatient substance use treatment should not be expected to decrease and increased use of telemedicine may be beneficial for this vulnerable population., Competing Interests: Conflicts of Interest The authors declare they have no conflicts of interest., (© 2020 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Sarcopenia, the age-associated loss of skeletal muscle mass and function, is coupled with declines in physical functioning leading to subsequent higher rates of disability, frailty, morbidity, and mortality. Aging and obesity independently contribute to muscle atrophy that is assumed to be a result of the activation of mutual physiological pathways. Understanding mechanisms contributing to the induction of skeletal muscle atrophy with aging and obesity is important for determining targets that may have pivotal roles in muscle loss in these conditions. We find that aging and obesity equally induce an anabolic resistance to acute skeletal muscle contraction as observed with decreases in anabolic signaling activation after contraction. Furthermore, treatment with the sphingosine-1-phosphate analog FTY720 for 4 wk increased lean mass and strength, and the anabolic signaling response to contraction was improved in obese but not older animals. To determine the role of chronic inflammation and different fatty acids on anabolic resistance in skeletal muscle cells, we overexpressed IKKβ with and without exposure to saturated fatty acid (SFA; palmitic acid), polyunsaturated fatty acid (eicosapentaenoic acid), and monounsaturated fatty acid (oleic acid). We found that IKKβ overexpression increased inflammation markers in muscle cells, and this chronic inflammation exacerbated anabolic resistance in response to SFA. Pretreatment with FTY720 reversed the inflammatory effects of palmitic acid in the muscle cells. Taken together, these data demonstrate chronic inflammation can induce anabolic resistance, SFA aggravates these effects, and FTY720 can reverse this by decreasing ceramide accumulation in skeletal muscle.

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 (SUV peak , SUV max , SUV max tumor /SUV mean 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.

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., (© 2019 The Authors.)

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.

Motivation: The discovery of relationships between gene expression measurements and phenotypic responses is hampered by both computational and statistical impediments. Conventional statistical methods are less than ideal because they either fail to select relevant genes, predict poorly, ignore the unknown interaction structure between genes, or are computationally intractable. Thus, the creation of new methods which can handle many expression measurements on relatively small numbers of patients while also uncovering gene-gene relationships and predicting well is desirable., Results: We develop a new technique for using the marginal relationship between gene expression measurements and patient survival outcomes to identify a small subset of genes which appear highly relevant for predicting survival, produce a low-dimensional embedding based on this small subset, and amplify this embedding with information from the remaining genes. We motivate our methodology by using gene expression measurements to predict survival time for patients with diffuse large B-cell lymphoma, illustrate the behavior of our methodology on carefully constructed synthetic examples, and test it on a number of other gene expression datasets. Our technique is computationally tractable, generally outperforms other methods, is extensible to other phenotypes, and also identifies different genes (relative to existing methods) for possible future study., Availability and Implementation: All of the code and data are available at http://mypage.iu.edu/∼dajmcdon/research/ ., Contact: dajmcdon@indiana.edu., Supplementary Information: Supplementary material is available at Bioinformatics online., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

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.

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.

The loss of skeletal muscle mass is observed in many pathophysiological conditions, including aging and obesity. The loss of muscle mass and function with aging is defined as sarcopenia and is characterized by a mismatch between skeletal muscle protein synthesis and breakdown. Characteristic metabolic features of both aging and obesity are increases in intramyocellular lipid (IMCL) content in muscle. IMCL accumulation may play a mechanistic role in the development of anabolic resistance and the progression of muscle atrophy in aging and obesity. In the present study, aged and high-fat fed mice were used to determine mechanisms leading to muscle loss. We hypothesized the accumulation of bioactive lipids in skeletal muscle, such as ceramide or diacylglycerols, leads to insulin resistance with aging and obesity and the inability to activate protein synthesis, contributing to skeletal muscle loss. We report a positive association between bioactive lipid accumulation and the loss of lean mass and muscle strength. Obese and aged animals had significantly higher storage of ceramide and diacylglycerol compared with young. Furthermore, there was an attenuated insulin response in components of the mTOR anabolic signaling pathway. We also observed differential increases in the expression of inflammatory cytokines and the phosphorylation of IκBα with aging and obesity. These data challenge the accepted role of increased inflammation in obesity-induced insulin resistance in skeletal muscle. Furthermore, we have now established IκBα with a novel function in aging-associated muscle loss that may be independent of its previously understood role as an NF-κB inhibitor.

A higher human immunodeficiency virus 1 (HIV-1) viral load at pleural sites infected with Mycobacterium tuberculosis (MTB) than in peripheral blood has been documented. However, the cellular source of productive HIV infection in HIV-1/MTB-coinfected pleural fluid mononuclear cells (PFMCs) remains unclear. In this study, we observed significant quantities of HIV-1 p24(+) lymphocytes in PFMCs, but not in peripheral blood mononuclear cells (PBMCs). HIV-1 p24(+) lymphocytes were mostly enriched in DN T cells. Intracellular CD4 expression was detectable in HIV-1 p24(+) DN T cells. HIV-1 p24(+) DN T cells showed lower surface expression of human leukocyte antigen (HLA)-ABC and tetherin than did HIV-1 p24(+) CD4 T cells. Upon in vitro infection of PFMC CD4 T cells from TB mono-infected subjects, Nef- and/or Vpu-deleted HIV mutants showed lower generation of HIV-1 p24(+) DN T cells than the wild-type virus. These data indicate that productively HIV-1-infected DN T cells, generated through down-modulation of surface CD4, likely by HIV-1 Nef and Vpu, are the predominant source of HIV-1 at pleural sites of HIV/MTB coinfection.

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., (© 2015 The Royal Australian and New Zealand College of Radiologists.)

Mycobacterium tuberculosis is an intracellular pathogen that infects lung macrophages and releases microbial factors that regulate host defense. M. tuberculosis lipoproteins and lipoglycans block phagosome maturation, inhibit class II MHC Ag presentation, and modulate TLR2-dependent cytokine production, but the mechanisms for their release during infection are poorly defined. Furthermore, these molecules are thought to be incorporated into host membranes and released from infected macrophages within exosomes, 40-150-nm extracellular vesicles that derive from multivesicular endosomes. However, our studies revealed that extracellular vesicles released from infected macrophages include two distinct, largely nonoverlapping populations: one containing host cell markers of exosomes (CD9, CD63) and the other containing M. tuberculosis molecules (lipoglycans, lipoproteins). These vesicle populations are similar in size but have distinct densities, as determined by separation on sucrose gradients. Release of lipoglycans and lipoproteins from infected macrophages was dependent on bacterial viability, implicating active bacterial mechanisms in their secretion. Consistent with recent reports of extracellular vesicle production by bacteria (including M. tuberculosis), we propose that bacterial membrane vesicles are secreted by M. tuberculosis within infected macrophages and subsequently are released into the extracellular environment. Furthermore, extracellular vesicles released from M. tuberculosis-infected cells activate TLR2 and induce cytokine responses by uninfected macrophages. We demonstrate that these activities derive from the bacterial membrane vesicles rather than exosomes. Our findings suggest that bacterial membrane vesicles are the primary means by which M. tuberculosis exports lipoglycans and lipoproteins to impair effector functions of infected macrophages and circulate bacterial components beyond the site of infection to regulate immune responses by uninfected cells., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Background: Chondroblastoma is a benign tumor classically located within the epiphysis of the long bones. The tumor is believed to arise from immature cells of the epiphyseal plate. Purely metaphyseal or diaphyseal chondroblastoma is exceedingly uncommon, occurring in approximately 2% of chondroblastoma cases. In all of these non-epiphyseal-based cases, the tumor has been intramedullary., Methods: We describe the histologic and imaging features of the first detailed description of a surface-based chondroblastoma., Results: The tumor was located in the anteromedial midshaft of the tibia in a 47-year-old male., Conclusion: We discuss the diagnostic considerations and possible etiology of chondroblastoma given this unusual location.

G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied receptors initiating the processes of desensitization and β-arrestin-dependent signaling. Interaction of GRKs with activated receptors serves to stimulate their kinase activity. The extreme N-terminal helix (αN), the kinase small lobe, and the active site tether (AST) of the AGC kinase domain have previously been implicated in mediating the allosteric activation. Expanded mutagenesis of the αN and AST allowed us to further assess the role of these two regions in kinase activation and receptor phosphorylation in vitro and in intact cells. We also developed a bioluminescence resonance energy transfer-based assay to monitor the recruitment of GRK2 to activated α(2A)-adrenergic receptors (α(2A)ARs) in living cells. The bioluminescence resonance energy transfer signal exhibited a biphasic response to norepinephrine concentration, suggesting that GRK2 is recruited to Gβγ and α(2A)AR with EC50 values of 15 nM and 8 μM, respectively. We show that mutations in αN (L4A, V7E, L8E, V11A, S12A, Y13A, and M17A) and AST (G475I, V477D, and I485A) regions impair or potentiate receptor phosphorylation and/or recruitment. We suggest that a surface of GRK2, including Leu(4), Val(7), Leu(8), Val(11), and Ser(12), directly interacts with receptors, whereas residues such as Asp(10), Tyr(13), Ala(16), Met(17), Gly(475), Val(477), and Ile(485) are more important for kinase domain closure and activation. Taken together with data on GRK1 and GRK6, our data suggest that all three GRK subfamilies make conserved interactions with G protein-coupled receptors, but there may be unique interactions that influence selectivity., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Unlabelled: CD4(+) and CD8(+) memory T cells with stem cell-like properties (T(SCM) cells) have been identified in mice, humans, and nonhuman primates and are being investigated for antitumor and antiviral vaccines and immunotherapies. Whether CD4(+) T(SCM) cells are infected by human immunodeficiency virus (HIV) was investigated by using a combination HIV reporter virus system in vitro and by direct staining for HIV p24 antigen ex vivo. A proportion of T(SCM) cells were found to express the HIV coreceptors CCR5 and CXCR4 and were infected by HIV both in vitro and in vivo. Analysis of viral outcome following fusion using the combination reporter virus system revealed that T(SCM) cells can become productively or latently infected, although the vast majority of T(SCM) cells are abortively infected. Knockdown of the HIV restriction factor SAMHD1 using Vpx-containing simian immunodeficiency virus (SIV) virion-like particles enhanced the productive infection of T(SCM) cells, indicating that SAMHD1 contributes to abortive infection in these cells. These results demonstrate that CD4(+) T(SCM) cells are targets for HIV infection, that they become productively or latently infected at low levels, and that SAMHD1 expression promotes abortive infection of this important memory cell subset., Importance: Here we demonstrate the susceptibility of CD4(+) memory stem cells (T(SCM) cells) to infection by HIV in vitro and in vivo, provide an in-depth analysis of coreceptor expression, demonstrate the infection of naïve and memory CD4(+) T cell subsets with both CCR5- and CXCR4-tropic HIV, and also perform outcome analysis to calculate the percentage of cells that are productively, latently, or abortively infected. Through these outcome studies, we determined that the vast majority of T(SCM) cells are abortively infected by HIV, and we demonstrate that knockdown of SAMHD1 significantly increases the frequency of infection of this CD4(+) T cell subset, indicating that SAMHD1 is an active restriction factor in T(SCM) cells.

Hemangiomas of the articular synovium are rare and commonly associated with recurrent joint swelling and painful limitation of motion. The knee joint is the most commonly involved site, with most patients diagnosed in the second to third decade of life. Although over 200 cases have been reported in the English-language medical literature, only three have originated within the hip joint, all of which were in adult patients reported in the surgical literature. We describe a histologically proven synovial hemangioma of the hip joint in a pediatric patient that invaded the femur, acetabulum, and adjacent soft tissues, with a detailed discussion of the differential diagnosis based on the radiographic and magnetic resonance imaging (MRI) findings.

Tuberculosis (TB) is the leading cause of mortality among those infected with human immunodeficiency virus (HIV-1) worldwide. HIV-1 load and heterogeneity are increased both locally and systemically in active TB. Mycobacterium tuberculosis (MTB) infection supports HIV-1 replication through dysregulation of host cytokines, chemokines, and their receptors. However the possibility that mycobacterial molecules released from MTB infected macrophages directly interact with CD4(+) T cells triggering HIV-1 replication has not been fully explored. We studied the direct effect of different MTB molecules on HIV-1 replication (R5-tropic strain Bal) in anti-CD3- stimulated CD4(+) T cells from healthy donors in an antigen presenting cell (APC)-free system. PIM6, a major glycolipid of the mycobacterial cell wall, induced significant increases in the percent of HIV-1 infected T cells and the viral production in culture supernatants. In spite of structural relatedness, none of the other three major MTB cell wall glycolipids had significant impact on HIV-1 replication in T cells. Increased levels of IFN-γ in culture supernatants from cells treated with PIM6 indicate that HIV-1 replication is likely dependent on enhanced T cell activation. In HEK293 cells transfected with TLR2, PIM6 was the strongest TLR2 agonist among the cell wall associated glycolipids tested. PIM6 increased the percentage of HIV infected cells and viral particles in the supernatant in a T-cell-based reporter cell line (JLTRg-R5) transfected with TLR1 and TLR2 but not in the cells transfected with the empty vector (which lack TLR2 expression) confirming that PIM6-induced HIV-1 replication depends at least partially on TLR2 signaling.

Background: Acetabular component malposition is linked to higher bearing surface wear and component instability. Outcomes following total hip arthroplasty and surface replacement arthroplasty depend on multiple surgeon and patient-dependent factors. The purpose of this study was to examine the frequency in which acetabular components are placed within a predetermined target range., Methods: We evaluated postoperative anteroposterior pelvic radiographs for every consecutive primary total hip arthroplasty and surface replacement arthroplasty completed from 2004 to 2009 at a single institution. Acetabular component abduction and anteversion angles were determined using Martell Hip Analysis Suite software. We defined target ranges for abduction and anteversion for both total hip arthroplasty (30° to 55° and 5° to 35°, respectively) and surface replacement arthroplasty (30° to 50° and 5° to 25°, respectively). Surgeon and patient-related factors were analyzed for risk associated with placing the acetabular component outside the target range., Results: Of the 1549 total hip arthroplasties, 1435 components (93%) met our abduction target, 1472 (95%) met our anteversion target, and 1363 (88%) simultaneously met both targets. Of the 263 surface replacement arthroplasties, 233 components (89%) met our abduction target, 247 (94%) met our anteversion target, and 220 (84%) simultaneously met both targets. When previously published target ranges of abduction (30° to 45°) and anteversion (5° to 25°) angles were used, only 665 total hip replacements (43%) met the abduction target, 1325 (86%) met the anteversion target, and 584 (38%) simultaneously met both targets. Of the surface replacement arthroplasties, 181 (69%) met the abduction target, 247 (94%) met the anteversion target, and 172 (65%) simultaneously met both targets. Low-volume surgeons were 2.16 times more likely to miss target component position compared with high-volume surgeons (p = 0.002). The odds of missing the target increased by ≥ 0.2 for every 5 kg/m2 increase in body mass index. Minimally invasive approaches, diagnosis, years of surgical experience, femoral head size, and age of the patient did not affect component position., Conclusions: Increased odds of component malposition were found with lower-volume surgeons and higher body mass index. No other variables had a significant effect on component placement., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

A case of right knee intra-articular synovial sarcoma in a 26-year-old man is reported. The patient had experienced 12 to 18 months of chronic posterior right knee pain with flexion contracture of the leg. Magnetic resonance imaging (MRI) examination demonstrated nonspecific characteristics of a well-circumscribed, homogeneous mass within the posterior lateral compartment of the knee joint. The mass was isointense and hyperintense to muscle on T1- and T2-weighted sequences respectively, and initially clinically diagnosed as a localized tenosynovial giant cell tumor. However, histological examination showed the lesion to be a synovial sarcoma arising from the synovium of the knee joint. Synovial sarcoma may have a nonspecific MR appearance, especially when less than 5 cm in size, often simulating a less aggressive process. Primary intra-articular origin may predispose to earlier presentation, and therefore, radiological evaluation of smaller masses. Nonspecific MR characteristics of small, intra-articular masses provide a diagnostic dilemma. Synovial sarcoma should be considered in the differential diagnosis when distinguishing MR characteristics of other common joint-centered entities are not present.

Background: Posterior pelvic ring reconstruction can be challenging and controversial. The choice regarding whether to reconstruct and how to reconstitute the pelvic ring is unclear. Many methods provide stability but often are technically difficult and require excessive dissection. DESCRIPTION OF SURGICAL TECHNIQUE: This unique reconstructive technique uses the anterior aspect of the iliac crest with its attached muscle pedicle to provide a biologic scaffold for healing. The construct is secured with pedicle screws into the posterior column and S1 vertebral body with a spinal rod locked in compression. No additional fixation is used proximally into the lumbar spine. The iliac crest remains attached to the gluteus medius, allowing potential abductor function., Methods: We retrospectively reviewed six patients who underwent iliosacral resection with this reconstruction. The mean age of the patients was 41 years. Complications were recorded. One patient died 6 months postoperatively. Musculoskeletal Tumor Society 1993 (MSTS '93) score and Toronto Extremity Salvage Score (TESS) were obtained at a minimum 1-year followup in five patients. Healing was assessed radiographically. The minimum followup was 6 months (median, 33 months; range, 6-53 months)., Results: The mean MSTS '93 score was 72% and mean TESS was 66. All posterior column graft sites healed. At last followup, four of the five surviving patients had a stable pseudarthrosis at the proximal sacral site. One patient had a local recurrence and experienced failure of instrumentation without collapse or rotation of the hemipelvis 3 years postoperatively., Conclusions: This technique provides a simple way to reconstruct the pelvic ring after iliosacral resection with clinical outcomes comparable to those for other methods. The method is a potential alternative for reconstruction of the posterior pelvic ring after resecting the ilium although reliable healing of the sacral site needs to be improved.

Background: As both cancer and major orthopaedic surgery are risk factors for venous thromboembolism, patients undergoing lower-extremity oncologic endoprosthetic arthroplasty for neoplastic processes are at substantial risk of the development of symptomatic venous thromboembolism. Therefore, the primary purpose of this study was to determine the incidence of symptomatic venous thromboembolism in patients undergoing lower-extremity oncologic endoprosthetic arthroplasty. Secondary purposes were to assess whether chemoprophylaxis influenced the incidence of venous thromboembolism, surgical complications, or the incidence of local sarcoma recurrence. We also sought to determine whether any known risk factors for venous thromboembolism could be identified in this patient population., Methods: We performed a retrospective comparative review of 423 patients who had undergone mega-endoprosthetic reconstruction following cancer resection. Univariate analysis was used to assess the association between chemoprophylaxis and the incidence of venous thromboembolism, to postulate the surgical complications associated with chemoprophylaxis, and to assess the rate of recurrence of local sarcoma as well the association between risk factors and venous thromboembolism., Results: Seventeen patients (4.0%) (95% confidence interval: 2.5% to 6.3%) had a venous thromboembolic event, ten with deep venous thrombosis and seven with nonfatal pulmonary embolism. Risk factors and chemoprophylactic regimens were not statistically associated with the occurrence of venous thromboembolism., Conclusions: The incidence of symptomatic venous thromboembolism in our group of cancer patients who underwent lower-extremity endoprosthetic arthroplasty was lower than anticipated. A significant difference was not identified between the use of any or no chemoprophylactic agent and the incidence of venous thromboembolism or complication rates. No risk factors were associated with the incidence of symptomatic venous thromboembolism.

The literature on statistical learning for time series assumes the asymptotic independence or "mixing" of the data-generating process. These mixing assumptions are never tested, and there are no methods for estimating mixing rates from data. We give an estimator for the beta-mixing rate based on a single stationary sample path and show it is L1-risk consistent.

The purposes of this study were to determine the spectrum of femoral head damage in patients undergoing revision total hip arthroplasty and to determine the impact of that damage on polyethylene wear. One hundred eight consecutive modular metal femoral heads were retrieved at revision surgery. The mean roughness (Ra) value was 0.18 +/- 0.18 microm. The roughest femoral heads (mean Ra, 0.56 microm) were from retrievals correlated with mode 2 wear (recurrent dislocation and complete wear through of the polyethylene liner). Five million cycles of wear tests were performed using retrieved femoral heads against both new conventional and highly cross-linked polyethylene. The mean wear rate of conventional polyethylene was 15.9 +/- 4.3 mg and that of highly cross-linked polyethylene was 0.04 +/- 0.14 mg per 1 million cycles (P < .001). Highly cross-linked polyethylene was more resistant to wear than conventional polyethylene, even when mated against roughened femoral heads., (Elsevier Inc. All rights reserved.)

As part of an investigation to identify potential new viral reduction strategies, ultraviolet-C (UV-C) light was examined. Although this technology has been known for decades to possess excellent virus inactivation capabilities, UV-C light can also introduce significant unwanted damage to proteins. To study the effect on monoclonal antibodies, three different antibodies were subjected to varying levels of UV-C light using a novel dosing device from Bayer Technology Services GmbH. The range of fluencies (or doses) covered was between 0 and 300 J/m(2) at a wavelength of 254 nm. Product quality data generated from the processed pools showed only minimal damage done to the antibodies. Aggregate formation was low for two of the three antibodies tested. Acidic and basic variants increased for all three antibodies, with the basic species increasing more than the acidic species. Peptide maps made for the three sets of pools showed no damage to two of the three antibody backbones, whereas the third antibody had very low levels of methionine oxidation evident. Samples held at 2-8 degrees C for 33 days showed no increase in aggregates or charge variants, indicating that the proteins did not degrade and were not damaged further by reactive or catalytic species that may have been created on exposure to UV-C light. Overall, UV-C light was shown to induce very little damage to monoclonal antibodies at lower fluencies and appears to be a viable option for viral inactivation in biotechnology applications., ((c) 2009 American Institute of Chemical Engineers Biotechnol.)

A total of 290 consecutive patients who underwent total hip and total knee arthroplasty were prospectively entered into a clinical anticoagulation trial using a 10-day course of Lovenox with the American College of Chest Physicians-1A guidelines. Major complications occurred in 9% of patients; symptomatic deep vein thrombosis occurred in 9 (3.8%) patients, and nonfatal pulmonary embolism in 3 (1.3%) patients. Complications included 4.7% readmissions, 3.4% return to the operating room for wound incision and drainage, 5.1% prolonged hospitalization (wound drainage), and 3.4% injection site complications. Wound drainage of more than 7 days was predictive of readmission and wound reoperation. A body mass index of more than 35 was predictive of prolonged wound drainage. Return to the operating room for wound complications occurred 3x more frequently with the use of Lovenox than in our previous study using warfarin. Surgical site complications requiring readmission or reoperation should be considered "major" complications.

Two adult patients are described with multifocal osteolytic lesions radiologically simulating a vascular tumor. One patient had multiple bones involved. Histologically, the individual lesions had the features of the nidus of osteoid osteoma/osteoblastoma. A review of the English language medical literature yielded only one other reported case with similar features. The process is designated as osteoblastomatosis to indicate its bone-forming character, prominent osteoblast proliferation, and multiplicity. The cases are distinguished from multifocal/multicentric osteoid osteoma and osteoblastoma, and from benign and malignant vascular tumors.