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Background and purpose The natural pattern of bone healing in large bony defects following curettage alone as treatment of benign bone tumors around the knee is not well reported. We analyzed the outcome in 146 patients. Patients and methods 146 patients with over 18 months of follow-up who underwent curettage without bone substitute filling or bone grafting for a benign tumor in the distal femur or upper tibia were included. The mean diameter of the defects following curettage was 5.7 (1.3-11) cm and the estimated average volume was 63 (1-240) cm(3). The plain radiographs before and following curettage were reviewed to establish the size of the initial defect and the rate of reconstitution and infilling of the bone. The time to full weight bearing and any complications were recorded. Results There was a variable rate of infilling; some defects completely reconstituted to a normal appearance while some never filled in. In 88% of the cases, no further intervention after curettage was required and the mean time to full weight bearing was 6 weeks. The risk of subsequent fracture or the late development of osteoarthritis was strongly related to the size of the cyst at diagnosis, with cysts of > 60 cm(3) (about 5 cm in diameter) having a much higher incidence of complications. Interpretation This study demonstrates the natural healing ability of bone without any adjuvant filling. It could be used as a baseline for future studies using any sort of filling with autograft, allograft, or bone substitute. [ABSTRACT FROM AUTHOR]

Background: Prosthetic replacement following excision of a bone tumor can be complicated by infection because patients who undergo surgery for a neoplastic condition often are subjected to extensive soft-tissue dissection and long operating times and are immunosuppressed. The aim of this study was to investigate the rate of periprosthetic infection, identify possible predisposing factors, and assess treatment efficacy in such patients.Methods: Prosthetic reconstruction was performed in 1264 patients over a thirty-seven-year period in a single hospital by four surgeons. Twenty-four patients were excluded because of incomplete follow-up, leaving 1240 patients who had been followed for a mean of 5.8 years. Infection was identified in 136 patients (11.0%). The management and outcome of the infections in all of these patients were analyzed.Results: Coagulase-negative Staphylococcus was the most common organism isolated. Two-stage revision successfully treated the infection in 72% (forty-two) of the fifty-eight patients in whom it was performed. Local surgical debridement with or without antibiotic implants was successful in only 6% (four) of sixty-eight patients. Amputation to treat the infection was performed in fifty (37%) of the 136 patients. The factors that were associated with a significant risk of infection (p Conclusions: Patients treated with an orthopaedic procedure for an oncological condition have high infection rates. The treatment of infection in these patients is arduous and lengthy, with a substantial risk of amputation. [ABSTRACT FROM AUTHOR]

Introduction. The "two-week wait" was established as a potential means of diagnosing malignant tumours earlier. This paper investigated whether these clinics are leading to earlier diagnosis of malignant soft-tissue lumps. Method. We identified all referrals to our centre from a database over a 4-year period. Results. 2225 patients were referred to our unit for investigation of a soft-tissue mass. 576 (26%) were referred under the "two-week wait" criteria. 153 (27%) of which were found to have a malignant or borderline malignant diagnosis. 1649 patients were referred nonurgently. 855 (52%) of which were diagnosed with a malignant or borderline lesion. The average size at diagnosis was 9.4 cm with no difference in size between the different referral routes. Conclusion. There is little evidence that the two-week wait clinic is leading to earlier diagnosis of soft-tissue sarcomas with the majority still being referred nonurgently. [ABSTRACT FROM AUTHOR]

Temporal dynamics play a central role in models of emotion: "fear" is widely conceptualized as a phasic response to certain-and-imminent danger, whereas "anxiety" is a sustained response to uncertain-or-distal harm. Yet the underlying human neurobiology remains contentious. Leveraging an ethnoracially diverse sample, translationally relevant paradigm, and theory-driven modeling approach, we demonstrate that certain and uncertain threat recruit a shared threat-anticipation circuit. This cortico-subcortical circuit exhibits persistently elevated activation when anticipating uncertain-threat encounters and a transient burst of activation in the moments before certain encounters. For many scientists and clinicians, feelings are the defining feature of human fear and anxiety. Here we used an independently validated brain signature to covertly decode the momentary dynamics of anticipatory distress for the first time. Results mirrored the dynamics of neural activation. These observations provide fresh insights into the neurobiology of threat-elicited emotions and set the stage for more ambitious clinical and mechanistic research.

Neuroticism/negative emotionality (N/NE)-the tendency to experience anxiety, fear, and other negative emotions-is a fundamental dimension of temperament with profound consequences for health, wealth, and well-being. Elevated N/NE is associated with a panoply of adverse outcomes, from reduced socioeconomic attainment to psychiatric illness. Animal research suggests that N/NE reflects heightened reactivity to uncertain threat in the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce), but the relevance of these discoveries to humans has remained unclear. Here we used a novel combination of psychometric, psychophysiological, and neuroimaging approaches to test this hypothesis in an ethnoracially diverse, sex-balanced sample of 220 emerging adults selectively recruited to encompass a broad spectrum of N/NE. Cross-validated robust-regression analyses demonstrated that N/NE is preferentially associated with heightened BST activation during the uncertain anticipation of a genuinely distressing threat (aversive multimodal stimulation), whereas N/NE was unrelated to BST activation during certain-threat anticipation, Ce activation during either type of threat anticipation, or BST/Ce reactivity to threat-related faces. It is often assumed that different threat paradigms are interchangeable assays of individual differences in brain function, yet this has rarely been tested. Our results revealed negligible associations between BST/Ce reactivity to the anticipation of threat and the presentation of threat-related faces, indicating that the two tasks are nonfungible. These observations provide a framework for conceptualizing emotional traits and disorders; for guiding the design and interpretation of biobank and other neuroimaging studies of psychiatric risk, disease, and treatment; and for refining mechanistic research., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Social anxiety-which typically emerges in adolescence-lies on a continuum and, when extreme, can be devastating. Socially anxious individuals are prone to heightened fear, anxiety, and the avoidance of contexts associated with potential social scrutiny. Yet most neuroimaging research has focused on acute social threat. Much less attention has been devoted to understanding the neural systems recruited during the uncertain anticipation of potential encounters with social threat. Here we used a novel fMRI paradigm to probe the neural circuitry engaged during the anticipation and acute presentation of threatening faces and voices in a racially diverse sample of 66 adolescents selectively recruited to encompass a range of social anxiety and enriched for clinically significant levels of distress and impairment. Results demonstrated that adolescents with more severe social anxiety symptoms experience heightened distress when anticipating encounters with social threat, and reduced discrimination of uncertain social threat and safety in the bed nucleus of the stria terminalis (BST), a key division of the central extended amygdala (EAc). Although the EAc-including the BST and central nucleus of the amygdala-was robustly engaged by the acute presentation of threatening faces and voices, the degree of EAc engagement was unrelated to the severity of social anxiety. Together, these observations provide a neurobiologically grounded framework for conceptualizing adolescent social anxiety and set the stage for the kinds of prospective-longitudinal and mechanistic research that will be necessary to determine causation and, ultimately, to develop improved interventions for this often-debilitating illness.

Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years. 1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT). 2 IT is a moderately heritable trait 1 that can be measured in multiple species. 3 In humans, levels of IT can be quantified from the first year of life through direct behavioral observations or reports by caregivers or teachers. Similar approaches as well as self-report questionnaires on current and/or retrospective levels of IT 1 can be used later in life., (Copyright © 2022 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Negative affect is a fundamental dimension of human emotion. When extreme, it contributes to a variety of adverse outcomes, from physical and mental illness to divorce and premature death. Mechanistic work in animals and neuroimaging research in humans and monkeys have begun to reveal the broad contours of the neural circuits governing negative affect, but the relevance of these discoveries to everyday distress remains incompletely understood. Here, we used a combination of approaches-including neuroimaging assays of threat anticipation and emotional-face perception and more than 10,000 momentary assessments of emotional experience-to demonstrate that individuals who showed greater activation in a cingulo-opercular circuit during an anxiety-eliciting laboratory paradigm experienced lower levels of stressor-dependent distress in their daily lives ( n s = 202-208 university students). Extended amygdala activation was not significantly related to momentary negative affect. These observations provide a framework for understanding the neurobiology of negative affect in the laboratory and in the real world.

The central goal of clinical psychology is to reduce the suffering caused by mental health conditions. Anxiety, mood, psychosis, substance use, personality, and other mental disorders impose an immense burden on global public health and the economy. Tackling this burden will require the development and dissemination of intervention strategies that are more effective, sustainable, and equitable. Clinical psychology is uniquely poised to serve as a transdisciplinary hub for this work. But rising to this challengerequires an honest reckoning with the strengths and weaknesses of current training practices. Building on new data, we identify the most important challenges to training the next generation of clinical scientists. We provide specific recommendations for the full spectrum of stakeholders-from funders, accreditors, and universities to program directors, faculty, and students-with an emphasis on sustainable solutions that promote scientific rigor and discovery and enhance the mental health of clinical scientists and the public alike.

When extreme, anxiety-a state of distress and arousal prototypically evoked by uncertain danger-can be debilitating. Uncertain anticipation is a shared feature of situations that elicit signs and symptoms of anxiety across psychiatric disorders, species, and assays. Despite the profound significance of anxiety for human health and wellbeing, the neurobiology of uncertain-threat anticipation remains unsettled. Leveraging a paradigm adapted from animal research and optimized for fMRI signal decomposition, we examined the neural circuits engaged during the anticipation of temporally uncertain and certain threat in 99 men and women. Results revealed that the neural systems recruited by uncertain and certain threat anticipation are anatomically colocalized in frontocortical regions, extended amygdala, and periaqueductal gray. Comparison of the threat conditions demonstrated that this circuitry can be fractionated, with frontocortical regions showing relatively stronger engagement during the anticipation of uncertain threat, and the extended amygdala showing the reverse pattern. Although there is widespread agreement that the bed nucleus of the stria terminalis and dorsal amygdala-the two major subdivisions of the extended amygdala-play a critical role in orchestrating adaptive responses to potential danger, their precise contributions to human anxiety have remained contentious. Follow-up analyses demonstrated that these regions show statistically indistinguishable responses to temporally uncertain and certain threat anticipation. These observations provide a framework for conceptualizing anxiety and fear, for understanding the functional neuroanatomy of threat anticipation in humans, and for accelerating the development of more effective intervention strategies for pathological anxiety. SIGNIFICANCE STATEMENT Anxiety-an emotion prototypically associated with the anticipation of uncertain harm-has profound significance for public health, yet the underlying neurobiology remains unclear. Leveraging a novel neuroimaging paradigm in a relatively large sample, we identify a core circuit responsive to both uncertain and certain threat anticipation, and show that this circuitry can be fractionated into subdivisions with a bias for one kind of threat or the other. The extended amygdala occupies center stage in neuropsychiatric models of anxiety, but its functional architecture has remained contentious. Here we demonstrate that its major subdivisions show statistically indistinguishable responses to temporally uncertain and certain threat. Collectively, these observations indicate the need to revise how we think about the neurobiology of anxiety and fear., (Copyright © 2020 the authors.)

Groin pain can be caused by a myriad of pathologies. Abnormalities of the rectus femoris are a very rare cause of groin pain; calcific tendinopathy of the direct head is particularly so, with only two case reports in the literature. We report the first case of calcific tendinopathy of the direct head of the rectus femoris that was treated effectively with ultrasound-guided percutaneous irrigation of calcific tendinopathy (USPICT). The anatomy of the rectus femoris and the technique for US-PICT of the rectus femoris are also described.

Borsboom et al. confuse biological approaches with extreme biological reductionism and common-cause models of psychopathology. In muddling these concepts, they mistakenly throw the baby out with the bathwater. Here, we highlight recent work underscoring the unique value of clinical and translational neuroscience approaches for understanding the nature and origins of psychopathology and for developing improved intervention strategies.

Aims: The aim of this paper was to investigate the prognostic factors for local recurrence in patients with pathological fracture through giant cell tumours of bone (GCTB)., Patients and Methods: A total of 107 patients presenting with fractures through GCTB treated at our institution (Royal Orthopaedic Hospital, Birmingham, United Kingdom) between 1995 and 2016 were retrospectively studied. Of these patients, 57 were female (53%) and 50 were male (47%).The mean age at diagnosis was 33 years (14 to 86). A univariate analysis was performed, followed by multivariate analysis to identify risk factors based on the treatment and clinical characteristics., Results: The initial surgical treatment was curettage with or without adjuvants in 55 patients (51%), en bloc resection with or without reconstruction in 45 patients (42%), and neoadjuvant denosumab, followed by resection (n = 3, 3%) or curettage (n = 4, 4%). The choice of treatment depended on tumour location, Campanacci tumour staging, intra-articular involvement, and fracture displacement. Neoadjuvant denosumab was used only in fractures through Campanacci stage 3 tumours. Local recurrence occurred in 28 patients (25%). Surgery more than six weeks after the fracture did not affect the risk of recurrence in any of the groups. In Campanacci stage 3 tumours not treated with denosumab, en bloc resection had lower local recurrences (13%), compared with curettage (39%). In tumours classified as Campanacci 2, intralesional curettage and en bloc resections had similar recurrence rates (21% and 24%, respectively). After univariate analysis, the type of surgical intervention, location, and the use of denosumab were independent factors predicting local recurrence. Further surgery was required 33% more often after intralesional curettage in comparison with resections (mean 1.59, 0 to 5 vs 1.06, 0 to 3 operations). All patients treated with denosumab followed by intralesional curettage developed local recurrence., Conclusion: In patients with pathological fractures through GCTB not treated with denosumab, en bloc resection offers lower risks of local recurrence in tumours classified as Campanacci stage 3. Curettage or resections are both similar options in terms of the risk of local recurrence for tumours classified as Campanacci stage 2. The benefits of denosumab followed by intralesional curettage in these patients still remains unclear.

Aims: The use of a noninvasive growing endoprosthesis in the management of primary bone tumours in children is well established. However, the efficacy of such a prosthesis in those requiring a revision procedure has yet to be established. The aim of this series was to present our results using extendable prostheses for the revision of previous endoprostheses., Patients and Methods: All patients who had a noninvasive growing endoprosthesis inserted at the time of a revision procedure were identified from our database. A total of 21 patients (seven female patients, 14 male) with a mean age of 20.4 years (10 to 41) at the time of revision were included. The indications for revision were mechanical failure, trauma or infection with a residual leg-length discrepancy. The mean follow-up was 70 months (17 to 128). The mean shortening prior to revision was 44 mm (10 to 100). Lengthening was performed in all but one patient with a mean lengthening of 51 mm (5 to 140)., Results: The mean residual leg length discrepancy at final follow-up of 15 mm (1 to 35). Two patients developed a deep periprosthetic infection, of whom one required amputation to eradicate the infection; the other required two-stage revision. Implant survival according to Henderson criteria was 86% at two years and 72% at five years. When considering revision for any cause (including revision of the growing prosthesis to a non-growing prosthesis), revision-free implant survival was 75% at two years, but reduced to 55% at five years., Conclusion: Our experience indicates that revision surgery using a noninvasive growing endoprosthesis is a successful option for improving leg length discrepancy and should be considered in patients with significant leg-length discrepancy requiring a revision procedure. Cite this article: Bone Joint J 2018;100-B:370-7.

The central extended amygdala (EAc)-including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)-plays a critical role in triggering fear and anxiety and is implicated in the development of a range of debilitating neuropsychiatric disorders. Although it is widely believed that these disorders reflect the coordinated activity of distributed neural circuits, the functional architecture of the EAc network and the degree to which the BST and the Ce show distinct patterns of functional connectivity is unclear. Here, we used a novel combination of imaging approaches to trace the connectivity of the BST and the Ce in 130 healthy, racially diverse, community-dwelling adults. Multiband imaging, high-precision registration techniques, and spatially unsmoothed data maximized anatomical specificity. Using newly developed seed regions, whole-brain regression analyses revealed robust functional connectivity between the BST and Ce via the sublenticular extended amygdala, the ribbon of subcortical gray matter encompassing the ventral amygdalofugal pathway. Both regions displayed coupling with the ventromedial prefrontal cortex (vmPFC), midcingulate cortex (MCC), insula, and anterior hippocampus. The BST showed stronger connectivity with the thalamus, striatum, periaqueductal gray, and several prefrontal territories. The only regions showing stronger functional connectivity with the Ce were neighboring regions of the dorsal amygdala, amygdalohippocampal area, and anterior hippocampus. These observations provide a baseline against which to compare a range of special populations, inform our understanding of the role of the EAc in normal and pathological fear and anxiety, and showcase image registration techniques that are likely to be useful for researchers working with "deidentified" neuroimaging data., (© 2017 Wiley Periodicals, Inc.)

Aims: The aim of this study was to analyse a group of patients with non-metastatic Ewing's sarcoma at presentation and identify prognostic factors affecting the development of local recurrence, in order to assess the role of radiotherapy., Patients and Methods: A retrospective review of all patients with a Ewing's sarcoma treated between 1980 and 2012 was carried out. Only those treated with chemotherapy followed by surgery and/or radiotherapy were included. Patients were grouped according to site (central or limb) for further analysis of the prognostic factors., Results: A total of 388 patients were included in the study. Of these, 60 (15%) developed local recurrence at a mean median of 27 months (sd 24, range 7 to 150) and the five-year local recurrence-free survival (5yrLRFS) was 83%. For central tumours, the size of the tumour and histological response to chemotherapy were found to be significant factors for local recurrence. For limb tumours, local recurrence was affected by intralesional and marginal resections, but not by the histological response to chemotherapy. Radiotherapy in those with a marginal resection reduced the risk of local recurrence (5yrLRFS: 96% versus 81%, p = 0.044)., Conclusion: Local recurrence significantly affects the overall survival in patients with a Ewing's sarcoma. For those with a tumour in a limb, radiotherapy reduced the risk of local recurrence, especially in those with a marginal margin of excision, but the effect in central tumours was less clear. Radiotherapy for those who have had a wide margin of resection does not reduce the risk of local recurrence, regardless of the histological response to chemotherapy. Cite this article: Bone Joint J 2018;100-B: 247-55., (©2018 The British Editorial Society of Bone & Joint Surgery.)

Aims: To investigate the impact of the method of treatment on the oncological outcomes in patients with epithelioid sarcomas managed at two international speciality sarcoma centres., Methods: The databases of two centres were used to identify patients treated for epithelioid sarcomas between 1985 and 2012. Patient, tumor, treatment and outcome data was collected., Results: There were 36 males and 18 females with a mean age of 38.3 years (range 9-79). Of 49 patients who were treated surgically, limb salvage surgery was carried out in 38 patients (78%) and limb amputation in 11 (22%). Of 49 total patients who underwent surgery for ES, 48 (98%) with ES had negative margin resection and 24 (49%) received (neo) adjuvant radiotherapy. Regional lymph node metastases developed in 5 (13%) patients. The five-year risk of local recurrence was 14%. The overall survival rate at five and ten years was 70% and 66% respectively. In multivariate analysis of patients with localized disease and negative margins, survival and risk of metastases was worse in those treated by amputation., Conclusion: This series has shown that although the rate of local recurrence is not influenced by the type of surgery, the risk of metastases is higher following amputation. This finding is likely due to patients with larger, deeper and more locally advanced tumors requiring amputation. However, we could not prove that immediate amputation was likely to affect overall survival., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The proximal tibia is one of the most challenging anatomic sites for extremity reconstructions after bone tumor resection. Because bone tumors are rare and large case series of reconstructions of the proximal tibia are lacking, we undertook this study to compare two major reconstructive approaches at two large sarcoma centers., Questions/purposes: The purpose of this study was to compare groups of patients treated with endoprosthetic replacement or osteoarticular allograft reconstruction for proximal tibia bone tumors in terms of (1) limb salvage reconstruction failures and risk of amputation of the limb; (2) causes of failure; and (3) functional results., Methods: Between 1990 and 2012, two oncologic centers treated 385 patients with proximal tibial resections and reconstruction. During that time, the general indications for those types of reconstruction were proximal tibia malignant tumors or bone destruction with articular surface damage or collapse. Patients who matched the inclusion criteria (age between 15 and 60 years old, diagnosis of a primary bone tumor of the proximal tibia treated with limb salvage surgery and reconstructed with endoprosthetic replacement or osteoarticular allograft) were included for analysis (n = 149). In those groups (endoprosthetic or allograft), of the patients not known to have reached an endpoint (death, reconstructive failure, or limb loss) before 2 years, 85% (88 of 104) and 100% (45 of 45) were available for followup at a minimum of 2 years. A total of 88 patients were included in the endoprosthetic group and 45 patients in the osteoarticular allograft group. Followup was at a mean of 9.5 (SD 6.72) years (range, 2-24 years) for patients with endoprosthetic reconstructions, and 7.4 (SD 5.94) years for patients treated with allografts (range, 2-21 years). The following variables were compared: limb salvage reconstruction failure rates, risk of limb amputation, type of failures according to the Henderson et al. classification, and functional results assessed by the Musculoskeletal Tumor Society system., Results: With the numbers available, after competitive risk analysis, the probability of failure for endoprosthetic replacement of the proximal tibia was 18% (95% confidence interval [CI], 10.75-27.46) at 5 years and 44% (95% CI, 31.67-55.62) at 10 years and for osteoarticular allograft reconstruction was 27% (95% CI, 14.73-40.16) at 5 years and 32% (95% CI, 18.65-46.18) at 10 years. There were no differences in terms of risk of failures at 5 years (p = 0.26) or 10 years (p = 0.20) between the two groups. Fifty-one of 88 patients (58%) with proximal tibia endoprostheses developed a reconstruction failure with mechanical causes being the most prevalent (32 of 51 patients [63%]). A total of 19 of 45 osteoarticular allograft reconstructions failed (42%) and nine of 19 (47%) of them were caused by early infection. Ten-year risk of amputation after failure for endoprosthetic reconstruction was 10% (95% CI, 5.13-18.12) and 11% (95% CI, 4.01-22.28) for osteoarticular allograft with no difference between the groups (p = 0.91). With the numbers available, there were no differences between the groups in terms of the mean Musculoskeletal Tumor Society score (26.58, SD 2.99, range, 19-30 versus 27.52, SD 1.91, range, 22-30; p = 0.13; 95% CI, -2,3 to 0.32). Mean extension lag was more severe in the endoprosthetic group than the osteoarticular allograft group: 13.56° (SD 18.73; range, 0°-80°) versus 2.41° (SD 5.76; range, 0°-30°; p < 0.001; 95% CI, 5.8-16.4)., Conclusions: Reconstruction of the proximal tibia with either endoprosthetic replacement or osteoarticular allograft appears to offer similar reconstruction failures rates. The primary cause of failure for allograft was infection and for endoprosthesis was mechanical complications. We believe that the treating surgeon should have both options available for treatment of patients with malignant or aggressive tumors of the proximal tibia. (S)he might consider an allograft in a younger patient to achieve better extensor mechanism function, whereas in an older patient or one with a poorer prognosis where return to function and ambulation quickly is desired, an endoprosthesis may be advantageous., Level of Evidence: Level III, therapeutic study.

Dispositional negativity-the propensity to experience and express more frequent, intense, or enduring negative affect-is a fundamental dimension of childhood temperament and adult personality. Elevated levels of dispositional negativity can have profound consequences for health, wealth, and happiness, drawing the attention of clinicians, researchers, and policymakers. Here, we highlight recent advances in our understanding of the psychological and neurobiological processes linking stable individual differences in dispositional negativity to momentary emotional states. Self-report data suggest that 3 key pathways-increased stressor reactivity, tonic increases in negative affect, and increased stressor exposure-explain most of the heightened negative affect that characterizes individuals with a more negative disposition. Of these 3 pathways, tonically elevated, indiscriminate negative affect appears to be most central to daily life and most relevant to the development of psychopathology. New behavioral and biological data provide insights into the neural systems underlying these 3 pathways and motivate the hypothesis that seemingly "tonic" increases in negative affect may actually reflect increased reactivity to stressors that are remote, uncertain, or diffuse. Research focused on humans, monkeys, and rodents suggests that this indiscriminate negative affect reflects trait-like variation in the activity and connectivity of several key brain regions, including the central extended amygdala and parts of the prefrontal cortex. Collectively, these observations provide an integrative psychobiological framework for understanding the dynamic cascade of processes that bind emotional traits to emotional states and, ultimately, to emotional disorders and other kinds of adverse outcomes. (PsycINFO Database Record, Competing Interests: Authors declare no conflicts of interest., ((c) 2016 APA, all rights reserved).)

Aims: Extendible endoprostheses have been available for more than 30 years and have become more sophisticated with time. The latest generation is 'non-invasive' and can be lengthened with an external magnetic force. Early results have shown a worryingly high rate of complications such as infection. This study investigates the incidence of complications and the need for further surgery in a cohort of patients with a non-invasive growing endoprosthesis., Patients and Methods: Between 2003 and June 2014, 50 children (51 prostheses) had a non-invasive growing prosthesis implanted for a primary bone sarcoma. The minimum follow-up was 24 months for those who survived. Their mean age was 10.4 years (6 to 14). The incidence of complications and further surgery was documented., Results: The mean follow-up was 64 months (20 to 145). The overall survivorship of the patients was 84% at three years and 70% at five years. Revision-free survival was 81.7% at three years and 61.6% at five years with competing risk analysis. Deep infection occurred in 19.6% of implants at a mean of 12.5 months (0 to 55). Other complications were a failure of the lengthening mechanism in five prostheses (9.8%) and breakage of the implant in two (3.9%). Overall, there were 53 additional operations (0 to 5 per patient). A total of seven patients (14%) underwent amputation, three for local recurrence and four for infection. Their mean limb length discrepancy was 4.3 mm (0 to 25) and mean Musculoskeletal Tumor Society Score functional score was 26.5 (18 to 30) at the final follow-up., Conclusions: When compared with previously published early results, this mid-term series has shown continued good functional outcomes and compensation for leg-length discrepancy. Infection is still the most common complication: post-operative wound healing problems, central line infection and proximal tibial location are the main risk factors. Cite this article: Bone Joint J 2016;98-B:1697-1703., (©2016 The British Editorial Society of Bone & Joint Surgery.)

We are reporting our experience on patients with -pelvic Ewing's Sarcoma treated in our unit. We retrospectively reviewed a series of patients with non-metastatic pelvic Ewing's sarcoma treated between 1977 and 2009. Patients were classified into three groups according to the local treatment received : Group 1. radiotherapy-chemo ; Group 2. surgery-chemo and Group 3. radiotherapy-surgery-chemo. Recurrence free and overall survival rates were calculated using the Kaplan-Meier method. Influence of various factors (age at diagnosis, gender, tumour site and size, chemotherapy response, surgical margins and type of treatment) on survival was assessed with a logistic regression model. A total of 85 patients were treated with a mean follow-up of 65.8 months and mean -tumour volume of 435ml. The 5-year survival for all patients was 40.7% decreased to 36.2% at 10 years. A significant prognostic factor identified was chemotherapy response only. There was a trend for improved survival and local control rates for patients who had chemotherapy and surgery and the results were apparent for all tumours irrespective of size but not statistically significant. Currently, the optimal management of pelvic Ewing's sarcoma is contro-versial but our study shows a trend for improved -survival for patients treated with chemotherapy and surgery.

When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the neurocognitive mechanisms that confer increased risk have only recently begun to come into focus. Here we review recent work highlighting the importance of neural circuits centered on the amygdala. We begin by describing dispositional negativity, a core dimension of childhood temperament and adult personality and an important risk factor for the development of anxiety disorders and other kinds of stress-sensitive psychopathology. Converging lines of epidemiological, neurophysiological, and mechanistic evidence indicate that the amygdala supports stable individual differences in dispositional negativity across the lifespan and contributes to the etiology of anxiety disorders in adults and youth. Hyper-vigilance and attentional biases to threat are prominent features of the anxious phenotype and there is growing evidence that they contribute to the development of psychopathology. Anatomical studies show that the amygdala is a hub, poised to govern attention to threat via projections to sensory cortex and ascending neuromodulatory systems. Imaging and lesion studies demonstrate that the amygdala plays a key role in selecting and prioritizing the processing of threat-related cues. Collectively, these observations provide a neurobiologically-grounded framework for understanding the development and maintenance of anxiety disorders in adults and youth and set the stage for developing improved intervention strategies., Competing Interests: Authors declare no conflicts of interest.

Purpose: The aim of the study was to report overall survival, local recurrence and development of metastasis in a group of patients with femur chondrosarcoma that presented with or without a pathological fracture., Methods: A retrospective review was performed, and 182 patients (39 pathological fractures) that had been treated by oncologic surgery for femoral chondrosarcoma were included. The mean age of the series was 50 years (range, eight to 90) and 114 patients were male (63%). Mean follow-up was 113 months (range, three to 216). Cancer-specific overall survival, development of metastasis and local recurrence were analysed, grouping patients by grade (grade I / grade 2-3 / dedifferentiated)., Results: Disease-specific survival in the entire group of chondrosarcoma of the femur was 69% (CI95% 63-76) at 5 years. Five-year disease-specific survival in the fracture group was 49% lower than in the control group 75% (p = 0.0001). Survival of patients with grade 1 chondrosarcoma with fracture was significantly less than those without fracture (p = 0.02) but there was no difference in those with grade 2-3 (p = 0.49) and dedifferentiated tumours (p = 0.09). The local recurrence rate of the entire series was 27%. Only dedifferentiated chondrosarcomas with an associated pathological fracture had a significantly higher rate of local recurrence. There was no relationship between development of metastases and fracture., Conclusion: A pathological fracture of the femur has a negative prognostic influence in grade 1 chondrosarcoma and increases the risk of local recurrence in dedifferentiated femur chondrosarcomas.

Aims: To investigate whether the oncological outcomes of patients with osteosarcomas in the upper distal extremity are similar to other sites and assess if limb-salvage surgery is safe in this location., Methods: The centre database was used to identify all patients with osteosarcomas in the lower humerus and distally between 1985 and 2012. Patient, tumor, treatment and outcome data was collected., Results: Twenty-six patients were included in this study. There were 9 males and 17 females with a mean age of 33 years (9-90). Seventeen osteosarcomas were located in the forearm bones (65%), six in the distal humerus (23%), and three (12%) in the hand. The three most common sub-diagnoses were parosteal 7/21 (33%), fibroblastic 4/21 (19%) and osteoblastic osteosarcomas 3/21 (14%). 2 patients (8%) had Paget's disease and 19 patients (73%) had high-grade tumors. Local excision was carried out in 12 patients (48%), 4 patients underwent endoprosthetic replacement (16%) and 9 underwent amputation (36%). The overall risk of local recurrence was 4% in our series. The five-year overall survival rate was 67%, with low tumor grade and parosteal type of osteosarcoma being positive predictors of survival., Conclusion: This series has shown that patients with high-grade osteosarcomas of the upper distal extremities have a higher amputation risk than other limb sites but have favorable outcomes with limb-salvage surgery, comparable to other anatomical sites. Parosteal osteosarcomas in particular have a good prognosis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We conducted a case-control study to examine the merit of silver-coated tumour prostheses. We reviewed 85 patients with Agluna-treated (silver-coated) tumour implants treated between 2006 and 2011 and matched them with 85 control patients treated between 2001 and 2011 with identical, but uncoated, tumour prostheses. In all, 106 men and 64 women with a mean age of 42.2 years (18.4 to 90.4) were included in the study. There were 50 primary reconstructions (29.4%); 79 one-stage revisions (46.5%) and 41 two-stage revisions for infection (24.1%). The overall post-operative infection rate of the silver-coated group was 11.8% compared with 22.4% for the control group (p = 0.033, chi-square test). A total of seven of the ten infected prostheses in the silver-coated group were treated successfully with debridement, antibiotics, and implant retention compared with only six of the 19 patients (31.6%) in the control group (p = 0.048, chi-square test). Three patients in the silver-coated group (3.5%) and 13 controls (15.3%) had chronic periprosthetic infection (p = 0.009, chi-square test). The overall success rates in controlling infection by two-stage revision in the silver-coated group was 85% (17/20) compared with 57.1% (12/21) in the control group (p = 0.05, chi-square test). The Agluna-treated endoprostheses were associated with a lower rate of early periprosthetic infection. These silver-treated implants were particularly useful in two-stage revisions for infection and in those patients with incidental positive cultures at the time of implantation of the prosthesis. Debridement with antibiotic treatment and retention of the implant appeared to be more successful with silver-coated implants., (©2015 The British Editorial Society of Bone & Joint Surgery.)

A poor response to chemotherapy (≤ 90% necrosis) for osteosarcomas leads to poorer survival and an increased risk of local recurrence, particularly if there is a close margin of excision. We evaluated whether amputation confers any survival benefit over limb salvage surgery (LSS) with narrow margins in patients who respond poorly to chemotherapy. We only analysed patients with an osteosarcoma of the limb, a poor response to chemotherapy and close margins on LSS (marginal/intralesional) or primary amputation: 360 patients (36 LSS (intralesional margins), 197 LSS (marginal margins) and 127 amputations) were included. Local recurrence developed in 13 (36%) following LSS with intralesional margins, and 39 (20%) following LSS with marginal margins. There was no local recurrence in patients who underwent amputation. The five-year survival for all patients was 41% (95% confidence interval (CI) 35 to 46), but for those treated by LSS with marginal margins was 46.2% (95% CI 38 to 53), 36.3% (95% CI 27 to 45) for those treated by amputation, and 28% (95 CI 14 to 44) for those treated by LSS with intralesional margins. Patients who had LSS and then developed local recurrence as a first event had the same survival as those who had primary amputation without local recurrence. Prophylactic adjuvant radiotherapy was used in 40 patients but had no discernible effect in preventing local recurrence. Although amputation offered better local control, it conferred no clear survival benefit over LSS with marginal margins in these patients with a poor overall prognosis., (©2015 The British Editorial Society of Bone & Joint Surgery.)

The aim of this study was to evaluate the functional and oncological outcome of extracorporeally irradiated autografts used to reconstruct the pelvis after a P1/2 internal hemipelvectomy. The study included 18 patients with a primary malignant bone tumour of the pelvis. There were 13 males and five females with a mean age of 24.8 years (8 to 62). Of these, seven had an osteogenic sarcoma, six a Ewing's sarcoma, and five a chondrosarcoma. At a mean follow-up of 51.6 months (4 to 185), nine patients had died with metastatic disease while nine were free from disease. Local recurrence occurred in three patients all of whom eventually died of their disease. Deep infection occurred in three patients and required removal of their graft in two while the third underwent a hindquarter amputation for extensive flap necrosis. The mean Musculoskeletal Tumor Society functional score of the 16 patients who could be followed-up for at least 12 months was 77% (50 to 90). Those 15 patients who completed the Toronto Extremity Salvage Score questionnaire had a mean score of 71% (53 to 85). Extracorporeal irradiation and re-implantation of bone is a valid method of reconstruction after an internal hemipelvectomy. It has an acceptable morbidity and a functional outcome that compares favourably with other available reconstructive techniques., (©2014 The British Editorial Society of Bone & Joint Surgery.)

Aims: The aim of this study was to clarify the clinical features and outcomes of diaphyseal osteosarcoma., Methods: Patients with newly-diagnosed high-grade osteosarcoma occurring in the long bone were eligible for this retrospective study. Clinicopathological information was collected from our database and compared with 36 diaphyseal, 405 proximal and 519 distal metaphyseal, and 14 whole bone osteosarcoma patients. Additionally, case-control study matching by age, gender, site, and metastatic status at diagnosis with 1:3 ratio of 36 diaphyseal to 108 metaphyseal osteosarcomas patients was also conducted., Results: Five-year overall survival and metastasis-free survival of the three groups including diaphyseal, metaphyseal, and whole bone osteosarcoma patients showed significant difference (P = .029 and P = .013, respectively), although there is no difference for the survivals between proximal and distal metaphyseal osteosarcoma patients. Case-control study showed that patients with diaphyseal osteosarcomas had a significantly larger tumour (mean 13.5 cm vs 10 cm, P = .026), and demonstrated higher pathologic fracture rate (28% vs 12%, P = .033), superior 5-year metastasis-free survival (74% vs 40%, P = .0068), and slightly better 5-year overall survival (68% vs 46%, P = .074). Prognostic factor analysis showed that a pathologic fracture significantly decreased the survival of the patients with diaphyseal osteosarcoma., Conclusions: The current study showed that diaphyseal osteosarcoma has distinct clinical features from metaphyseal osteosarcoma having an increased risk of pathologic fractures but with favorable survival outcome., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The prevalence of deformational plagiocephaly has risen dramatically in recent years, now affecting 15 percent or more of infants. Prior research using developmental scales suggests that these children may be at elevated risk for developmental delays. However, the low positive predictive value of such instruments in identifying long-term impairment, coupled with their poor reliability in infants, warrants the development of methods to more precisely measure brain function in craniofacial patients. Event-related potentials offer a direct measure of cortical activity that is highly applicable to young populations and has been implemented in other disorders to predict long-term cognitive functioning. The current study used event-related potentials to contrast neural correlates of auditory perception in infants with deformational plagiocephaly and typically developing children., Methods: Event-related potentials were recorded while 16 infants with deformational plagiocephaly and 18 nonaffected controls passively listened to speech sounds. Given prior research suggesting their association with subsequent functioning, analyses focused on the P150 and N450 event-related potential components., Results: Deformational plagiocephaly patients and normal controls showed comparable cortical responses to speech sounds at both auditory event-related potential components., Conclusions: Children with deformational plagiocephaly demonstrate neural responses to language that are consistent with normative expectations and comparable to those of typical children. These results indicate that head shape deformity secondary to supine sleep is not associated with impairments in auditory processing. The applicability of the current methods in early infancy suggests that electrophysiologic brain recordings represent a promising method of monitoring brain development in children with cranial disorders., Clinical Question/level of Evidence: Risk, II.

Background: Surgery remains the main treatment of bone metastases due to renal cell carcinoma (RCC). We reviewed 135 patients treated with resection and endoprosthetic replacement (EPR) and examined clinico-pathological factors predicting survival., Methods: Surgical and oncological outcomes were examined using a prospectively maintained database between 1976 and 2012. Survival rates were calculated by Kaplan-Meier method. Multivariate analyses were performed to investigate factors predictive of increased survival., Results: At diagnosis, 81 patients had synchronous RCC and bone metastases and the remaining developed metachronous metastases after primary treatment for RCC. The majority were solitary tumours (75%) and 77% had ≥ one concurrent visceral metastases. The median age at surgery was 61 years old (IQR 53-69). The median follow-up was 20 months (IQR 10-43) and the overall survival was 72% at one-year. This declined to 45% and 28% at three and five-years, respectively. After adjustments for prognostic factors, there was an increased risk of death in patients with multiple skeletal metastases (HR = 2), ≥one visceral metastases (HR = 3) and local recurrence (HR = 3) (all p ≤ 0.01). Ten patients required revision (7%) and the risk of revision was 4% at one-year and remained low at 8% from two years postoperatively., Conclusion: Patients with solitary bone lesions and no visceral metastases should be considered for bone resection and EPR. As survival beyond one-year can be expected in a majority of patients and the risk of further surgery after EPR is low, patients with multiple skeletal metastases and visceral metastases should also be considered., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The purpose of this study was to assess whether the use of a joint-sparing technique such as curettage and grafting was successful in eradicating giant cell tumours of the proximal femur, or whether an alternative strategy was more appropriate. Between 1974 and 2012, 24 patients with a giant cell tumour of the proximal femur were treated primarily at our hospital. Treatment was either joint sparing or joint replacing. Joint-sparing treatment was undertaken in ten patients by curettage with or without adjunctive bone graft. Joint replacement was by total hip replacement in nine patients and endoprosthetic replacement in five. All 11 patients who presented with a pathological fracture were treated by replacement. Local recurrence occurred in five patients (21%): two were treated by hip replacement, three by curettage and none with an endoprosthesis. Of the ten patients treated initially by curettage, six had a successful outcome without local recurrence and required no further surgery. Three eventually needed a hip replacement for local recurrence and one an endoprosthetic replacement for mechanical failure. Thus 18 patients had the affected joint replaced and only six (25%) retained their native joint. Overall, 60% of patients without a pathological fracture who were treated with curettage had a successful outcome.

Purpose: We report on a group of patients with tumours in the Hoffa's fat pad (HFP), their clinical presentation, histological type and treatment, including two synovial sarcomas with their clinical follow-up, which have not been described previously in the literature., Methods: We performed a retrospective review of our prospectively collected database of 25 cases of HFP tumours with at least six months follow-up., Results: The gender, age at presentation (over and under 16 years of age), clinical features, history of trauma, treatment chosen, and complications were recorded. The mean age of the patients was 32 years (three to 47). Six patients were under 16 years old. Pain was the most common symptom, present in 92% (n = 23/25). The final diagnoses included 23 (92%) benign tumours and two (8%) malignant tumours. The most common benign tumour was pigmented villonodular synovitis (PVNS) (48% n = 12). The two malignant tumours were synovial sarcomas and both presented in patients under 16 years old., Conclusions: Hoffa's fat pad tumours are an uncommon and rarely diagnosed group of lesions that can be misinterpreted as any knee pathology. Although the majority of HFP tumours are benign, malignant tumours should be considered in the differential diagnosis for the paediatric population.

Aims: The treatment of pelvic soft tissue sarcomas (STS) presents one of the most challenging problems in musculoskeletal oncology because of the complex anatomy of the pelvis, late diagnosis and large tumor size. Our study was designed to determine the outcome and prognostic factors for survival and local recurrence in patients with pelvic STS located deep to the fascia and deemed suitable for curative surgical treatment., Patients and Methods: Ninety consecutive pelvic STS patients with at least 5-year possible follow-up from diagnosis were studied. Mean age at diagnosis was 54 years. Mean follow-up and tumor size were 69 months and 13 cm, respectively. Histological grades were grade 3 in 51, grade 2 in 22 and grade 1 in 17 patients. Tumor locations were extra-pelvic or outside pelvic brim (n=67), intra-pelvic or within pelvic brim (n=10), and combined or involving both outside and within pelvic brim (n=13)., Result: Surgical treatment was excision in 84 patients and hindquarter amputation in 6 patients. In 84 patients who underwent excision, surgical margin was wide in 21 patients, marginal in 33, and intralesional in 30. Radiotherapy was used for all high grade tumors. Disease-specific survival was 53.3% at 5 years. Local recurrence occurred in 23%. Development of local recurrence was related to surgical margin (p=0.03). Local recurrence, tumor histological grade and metastasis at diagnosis independently influenced disease-specific survival (p=0.0008, p<0.0001, p=0.02, respectively)., Conclusion: The patients with high grade tumors and positive surgical margins represent a particular group with high risk of local recurrence even with radiotherapy., (Copyright © 2012. Published by Elsevier Ltd.)

We evaluated the risk of late relapse and further outcome in patients with soft-tissue sarcomas who were alive and event-free more than five years after initial treatment. From our database we identified 1912 patients with these pathologies treated between 1980 and 2006. Of these 1912 patients, 603 were alive and event-free more than five years after initial treatment and we retrospectively reviewed them. The mean age of this group was 48 years (4 to 94) and 340 were men. The mean follow-up was 106 months (60 to 336). Of the original cohort, 582 (97%) were alive at final follow-up. The disease-specific survival was 96.4% (95% confidence interval (CI) 94.4 to 98.3) at ten years and 92.9% (95% CI 89 to 96.8) at 15 years. The rate of late relapse was 6.3% (38 of 603). The ten- and 15-year event-free rates were 93.2% (95% CI 90.8 to 95.7) and 86.1% (95% CI 80.2 to 92.1), respectively. Multivariate analysis showed that tumour size and tumour grade remained independent predictors of events. In spite of further treatment, 19 of the 38 patients died of sarcoma. The three- and five-year survival rates after the late relapse were 56.2% (95% CI 39.5 to 73.3) and 43.2% (95% CI 24.7 to 61.7), respectively, with a median survival time of 46 months. Patients with soft-tissue sarcoma, especially if large, require long-term follow-up, especially as they have moderate potential to have their disease controlled.

Purpose: We report the outcome of intercalary resection of the femoral diaphysis and extracorporeal irradiated autologous bone graft reconstruction, without the use of vascularized fibular graft., Methods: Six patients with Ewing sarcoma of the mid-shaft femur who were treated by limb sparing tumour resection and reconstruction with extracorporeal irradiated autologous bone graft with intramedullary cement between 2002 and 2010 were studied., Results: Mean age at the time of surgery was ten years (range, four-23). The length of resected femoral bone averaged 23 cm (15-32 cm). The ratio of bone resection length to total femoral length averaged 60 % (56-66 %). The patients had been followed up for between 16 and 79 months (mean, 41 months) at the time of the study. There was no infection nor fracture in this series. Primary union of the distal and proximal osteotomy sites was achieved in three patients. Delayed union of the proximal osteotomy site occurred in one patient that was successfully treated with iliac crest bone grafting. One patient developed non-union at the distal osteotomy site which failed to heal with bone grafting and was therefore converted to endoprosthetic replacement, and another patient was converted to rotationplasty at five months post-surgery because of contaminated margins. Function was excellent in all patients with surviving re-implanted bone. Local recurrence arose in one patient., Conclusion: Our experience suggests that cement augmentation of extracorporeal irradiated and re-implanted bone autografts offer a useful method of reconstructing large femoral diaphyseal bone defects after excision of primary malignant bone tumours.