UK guidelines for the management of bone sarcomas

This document is an update of the British Sarcoma Group guidelines published in 2010. The aim is to provide a reference standard for the clinical care of patients in the UK with bone sarcomas. Recent recommendations by the European Society of Medical Oncology, The National Comprehensive Cancer Network and The National Institute for Health and Care Excellence have been incorporated, and the literature since 2010 reviewed. The standards represent a consensus amongst British Sarcoma Group members in 2015. It is acknowledged that these guidelines will need further updates as care evolves. The key recommendations are that bone pain or a palpable mass should always lead to further investigation and that patients with clinico-radiological findings suggestive of a primary bone tumour at any site in the skeleton should be referred to a specialist centre and managed by a fully accredited bone sarcoma multidisciplinary team. Treatment recommendations are provided for the major tumour types and for localised, metastatic and recurrent disease. Follow up schedules are suggested.     

The role of tryptophan metabolism in postpartum depression

The Postpartum depression (PPD) is the most common postpartum psychiatric disorder, afflicting approximately 10%–20% of new mothers. Clinical symptoms of the PPD include depressive disorder, agitation, insomnia, anxiety and confusion, resulting in an increase in suicidal tendencies, thereby having significant impacts on the puerpera, newborn and their family. A growing body of data indicate a role for alterations in tryptophan metabolism in the PPD. The metabolism of tryptophan produces an array of crucial factors that can differentially regulate key physiological processes linked to the PPD. Importantly, an increase in stress hormones and immune-inflammatory activity drives tryptophan to the production of neuroregulatory kynurenine pathway products and away from the serotonin and melatonin pathways. This links the PPD to other disorders of depressed mood, which are classically associated with decreased serotonin and melatonin, coupled to increases in kynurenine pathway products. Several kynurenine pathway products, such as kynurenic acid and quinolinic acid, can have neuroregulatory effects, with consequences pathological underpinnings of the PPD. The current article reviews the role of alterations in tryptophan metabolism in the PPD.     

Spinal fractures in patients with ankylosing spondylitis

The ankylosed spine is prone to fracture even after minor trauma due to its changed biomechanical properties. The two central features of ankylosing spondylitis (AS) that promote the pathological remodeling of the spine are inflammation and new bone formation. AS is also associated with osteoporosis that is attributed to an uncoupling of the bone formation and bone resorption processes. Therefore, bone resorption occurs and promotes weakening of the spine as well as increased risk of vertebral fractures which can be hugely different in terms of clinical relevance. Even in the presence of symptomatic clinical vertebral fractures, the diagnosis can be overruled by attributing the pain to disease activity. Furthermore, given the highly abnormal structure of the spine, vertebral fracture diagnosis can be difficult on the basis of radiography alone. CT can show the fractures in detail. Magnetic resonance imaging is considered the method of choice for the imaging of spinal cord injuries, and a reasonable option for exclusion of occult fractures undetected by CT. Since it is equally important for radiologists and clinicians to have a common knowledge base rather than a compartmentalized view, the aim of this review article was to provide the required clinical knowledge that radiologists need to know and the relevant radiological semiotics that clinicians require in diagnosing clinically significant injury to the ankylosed spine.     

Individualized prophylaxis for optimizing hemophilia care: can we apply this to both developed and developing nations?

Prophylaxis is considered optimal care for hemophilia patients to prevent bleeding and to preserve joint function thereby improving quality of life (QoL). The evidence for prophylaxis is irrefutable and is the standard of care in developed nations. Prophylaxis can be further individualized to improve outcomes and cost effectiveness. Individualization is best accomplished taking into account the bleeding phenotype, physical activity/lifestyle, joint status, and pharmacokinetic handling of specific clotting factor concentrates, all of which vary among individuals. Patient acceptance should also be considered. Assessment tools (e.g. joint status imaging and function studies/scores, QoL) for determining and monitoring risk factors and outcome, as well as population PK profiling have been developed to assist the individualization process. The determinants of optimal prophylaxis include (1) factor dose/dosing frequency, hence, cost/affordability (2) bleeding triggers (physical activity/lifestyle, chronic arthropathy and synovitis) and (3) bleeding rates. Altering one determinant results in adjustment of the other two. Thus, the trough level to protect from spontaneous bleeding can be increased in patients who have greater bleeding risks; and prophylaxis to achieve zero joint bleeds is achievable through optimal individualization. Prophylaxis in economically constrained nations is limited by the ill-affordability of clotting factor concentrates. However, at least 5 studies on children and adults from Thailand, China and India have shown superiority of low dose (~5–10 IU kg^?1 2-3× per week) prophylaxis over episodic treatment in terms of bleed reduction, and quality of life, with improved physical activity, independent functioning, school attendance and community participation. In these nations, the prophylaxis goals should be for improved QoL rather than “zero bleeds” and perfect joints. Prophylaxis can still be individualized to affordability. Higher protective trough level can be achieved by using smaller doses given more frequently without an increase in consumption/cost. The bleeding trigger can also be down-regulated by avoiding unnecessary injury, and by engaging in judicious strengthening exercises appropriate to the joint status to improve balance and joint stabilization. Central to the success of prophylaxis are clinics with comprehensive care that provide the necessary professional expertise, support, and counseling, to educate patients, families, and other healthcare professionals, and to support research for improved hemophilia care.     

Increasing Valid Profiles in Phallometric Assessment of Sex Offenders with Child Victims: Combining the Strengths of Audio Stimuli and Synthetic Characters

Penile plethysmography (PPG) is a measure of sexual interests that relies heavily on the stimuli it uses to generate valid results. Ethical considerations surrounding the use of real images in PPG have further limited the content admissible for these stimuli. To palliate this limitation, the current study aimed to combine audio and visual stimuli by incorporating computer-generated characters to create new stimuli capable of accurately classifying sex offenders with child victims, while also increasing the number of valid profiles. Three modalities (audio, visual, and audiovisual) were compared using two groups (15 sex offenders with child victims and 15 non-offenders). Both the new visual and audiovisual stimuli resulted in a 13% increase in the number of valid profiles at 2.5 mm, when compared to the standard audio stimuli. Furthermore, the new audiovisual stimuli generated a 34% increase in penile responses. All three modalities were able to discriminate between the two groups by their responses to the adult and child stimuli. Lastly, sexual interest indices for all three modalities could accurately classify participants in their appropriate groups, as demonstrated by ROC curve analysis (i.e., audio AUC = .81, 95% CI [.60, 1.00]; visual AUC = .84, 95% CI [.66, 1.00], and audiovisual AUC = .83, 95% CI [.63, 1.00]). Results suggest that computer-generated characters allow accurate discrimination of sex offenders with child victims and can be added to already validated stimuli to increase the number of valid profiles. The implications of audiovisual stimuli using computer-generated characters and their possible use in PPG evaluations are also discussed.