The abscopal effect: a sense of DNA damage is in the air

Tumor metastasis is a singularly important determinant of survival in most cancers. Historically, radiation therapy (RT) directed at a primary tumor mass was associated infrequently with remission of metastasis outside the field of irradiation. This away-from-target or “abscopal effect” received fringe attention because of its rarity. With the advent of immunotherapy, there are now increasing reports of abscopal effects upon RT in combination with immune checkpoint inhibition. This sparked investigation into underlying mechanisms and clinical trials aimed at enhancement of this effect. While these studies clearly attribute the abscopal effect to an antitumor immune response, the initial molecular triggers for its onset and specificity remain enigmatic. Here, we propose that DNA damage–induced inflammation coupled with neoantigen generation is essential during this intriguing phenomenon of systemic tumor regression and discuss the implications of this model for treatment aimed at triggering the abscopal effect in metastatic cancer.     

A systematic review of injuries in gymnastics

Objectives: To identify all studies of gymnastics injuries and assess injury rates, types, locations, and causes.

Methods: Seven electronic and two grey literature databases were searched. Two reviewers independently assessed titles/abstracts, abstracted data, and calculated average rates weighted by study size.

Results: One study (n = 963) of three Olympic games (2008,2012,2016) provided injury rates for females of 86.4/1000gymnasts and males 79.9. For 29 databases one study of males (n = 64) provided a rate of 8.8 injuries/1000hours/AE (AE = athletic-exposure) and three of females varied rates (8.5, 9.4, and 91). Three studies for males (n = 153) provided a weighted average rate of 1.4 injuries/1000hours/training, and for females six studies (n = 476) 1.5 injuries. Four studies of males (n = 286) provided a weighted average of 678 injuries/1000gymnasts per year and eight studies of females (n = 1,764) a rate of 306. Of 19 surveys, eight provided rates for females (n = 1,463) of 596 injuries/gymnast per year and two for males (n = 40) a rate of 1,036. In the Olympics injuries were preponderately lower limb (63%) then trunk (23%) and upper limb (14%); injury type was sprains (35%) followed by tendinopathy/arthritis/impingements (17%), contusions (10%), and fractures (7%). Five database studies provided injury location data for 274 males: averages weighted by study size were upper extremity 42.8%, lower extremity 33.6%, torso/spine 11.8%, and head/neck 4.9% and 12 studies with 843 females provided average rates for lower extremity 51%, upper extremity 30.8%, torso/spine 13% and head/neck 0.8%. Official gymnastics organizations’ websites provide no readily available data about injury rates or methods of prevention.

Conclusions: Studies need to collect comprehensive data for injury rates by training/competitions, gender, age, injury location/type/cause. Studies could assess whether trainers and physiotherapists monitoring gymnasts closely for injury risk would reduce injuries. Studies including randomized controlled trials (RCTs) of interventions in training, videotaping and performance feedback to reduce injury rates would be helpful.     

Safe and Appropriate Use of Methadone in Hospice and Palliative Care: Expert Consensus White Paper

Methadone has several unique characteristics that make it an attractive option for pain relief in serious illness, but the safety of methadone has been called into question after reports of a disproportionate increase in opioid-induced deaths in recent years. The American Pain Society, College on Problems of Drug Dependence, and the Heart Rhythm Society collaborated to issue guidelines on best practices to maximize methadone safety and efficacy, but guidelines for the end-of-life scenario have not yet been developed. A panel of 15 interprofessional hospice and palliative care experts from the U.S. and Canada convened in February 2015 to evaluate the American Pain Society methadone recommendations for applicability in the hospice and palliative care setting. The goal was to develop guidelines for safe and effective management of methadone therapy in hospice and palliative care. This article represents the consensus opinion of the hospice and palliative care experts for methadone use at end of life, including guidance on appropriate candidates for methadone, detail in dosing, titration, and monitoring of patients' response to methadone therapy.