The sex gap in bladder cancer survival - a missing link in bladder cancer care?

The differences in bladder cancer outcomes between the sexes has again been highlighted. Uncommon among cancers, bladder cancer outcomes are notably worse for women than for men. Furthermore, bladder cancer is three to four times more common among men than among women. Factors that might explain these sex differences include understanding the importance of haematuria as a symptom of bladder cancer by both clinicians and patients, the resultant delays in diagnosis and referral of women with haematuria, and health-care access. Notably, these factors seem to have geographical variation and are not consistent across all health-care systems. Likewise, data relating to sex-specific treatment responses for patients with non-muscle-invasive or muscle-invasive bladder cancer are inconsistent. The influence of differences in the microbiome, bladder wall thickness and urine dwell times remain to be elucidated. The interplay of hormone signalling, gene expression, immunology and the tumour microenvironment remains complex but probably underpins the sexual dimorphism in disease incidence and stage and histology at presentation. The contribution of these biological phenomena to sex-specific outcome differences is probable, albeit potentially treatment-specific, and further understanding is required. Notwithstanding these aspects, we identify opportunities to harness biological differences to improve treatment outcomes, as well as areas of fundamental and translational research to pursue. At the level of policy and health-care delivery, improvements can be made across the domains of patient awareness, clinician education, referral pathways and guideline-based care. Together, we aim to highlight opportunities to close the sex gap in bladder cancer outcomes.

Robotic Resection of Left Atrial Myxoma With Cryoablation of Tumor Stalk.

The purpose of this report is to demonstrate robotic cryoablation of an atrial myxoma stalk as a method to prevent recurrence and preserve atrial tissue. A 38-year-old female patient was taken to the operating room, and an atrial myxoma abutting the left inferior pulmonary vein was resected robotically. This was followed by cryoablation of the tumor stalk instead of a full-thickness resection to prevent an extensive reconstruction. The operation resulted in the successful resection of an atrial myxoma with minimal length of stay. Follow-up at 3 months has shown no evidence of residual or recurrent tumor. Follow-up at 1 year is planned. Cryoablation of an atrial myxoma stalk, when resection would require complex reconstruction, is a useful tool in the armamentarium of a minimally invasive cardiac surgeon.

Activity and toxicity of intramuscular 1000 iu/m2 polyethylene glycol-E. coli L-asparaginase in the UKALL 2003 and UKALL 2011 clinical trials.

In successive UK clinical trials (UKALL 2003, UKALL 2011) for paediatric acute lymphoblastic leukaemia (ALL), polyethylene glycol-conjugated E. coli L-asparaginase (PEG-EcASNase) 1000 iu/m2 was administered intramuscularly with risk-stratified treatment. In induction, patients received two PEG-EcASNase doses, 14 days apart. Post-induction, non-high-risk patients (Regimens A, B) received 1-2 doses in delayed intensification (DI) while high-risk Regimen C patients received 6-10 PEG-EcASNase doses, including two in DI. Trial substudies monitored asparaginase (ASNase) activity, ASNase-related toxicity and ASNase-associated antibodies (total, 1112 patients). Median (interquartile range) trough plasma ASNase activity (14 ± 2 days post dose) following first and second induction doses and first DI dose was respectively 217 iu/l (144-307 iu/l), 265 iu/l (165-401 iu/l) and 292 iu/l (194-386 iu/l); 15% (138/910) samples showed subthreshold ASNase activity (<100 iu/l) at any trough time point. Older age was associated with lower (regression coefficient -9.5; p < 0.0001) and DI time point with higher ASNase activity (regression coefficient 29.9; p < 0.0001). Clinical hypersensitivity was observed in 3.8% (UKALL 2003) and 6% (UKALL 2011) of patients, and in 90% or more in Regimen C. A 7% (10/149) silent inactivation rate was observed in UKALL 2003. PEG-EcASNase schedule in UKALL paediatric trials is associated with low toxicity but wide interpatient variability. Therapeutic drug monitoring potentially permits optimisation through individualised asparaginase dosing.

Transbronchial Lung Cryobiopsy in Idiopathic Pulmonary Fibrosis: A State of the Art Review.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease associated with significant morbidity and mortality. The diagnosis of IPF involves a combination of clinical history, radiological imaging and examination of histopathological samples in appropriate cases. Historically, transbronchial biopsy (TBB) has been used to obtain histological samples; however this lacks diagnostic accuracy. At present, surgical lung biopsy (SLB) is the gold standard technique for obtaining specimen samples; however this carries a significant mortality risk. Transbronchial lung cryobiopsy (TBLC) is a new technique that has been pioneered in the management of lung malignancy and offers a potential alternative to SLB. The technique employs a freezing probe, which is used to obtain lung tissue samples that are larger and better quality than traditional TBB samples. This affords TBLC an estimated diagnostic yield of 80% in interstitial lung disease. However, with limited evidence directly comparing TBLC to SLB, the diagnostic accuracy of the procedure has been uncertain. Common complications of TBLC include pneumothorax and bleeding. Mortality in TBLC is low compared with SLB, with exacerbation of IPF frequently reported as the cause. TBLC represents an exciting potential option in the diagnostic pathway in IPF; however its true value has yet to be determined.

Repetitive Transcranial Magnetic Stimulation: a Novel Approach for Treating Oropharyngeal Dysphagia.

In recent years, repetitive transcranial magnetic stimulation, a technique used to produce human central neurostimulation, has attracted increased interest and been applied experimentally in the treatment of dysphagia. This review presents a synopsis of the current research for the application of repetitive transcranial magnetic stimulation (rTMS) on dysphagia. Here, we review the mechanisms underlying the effects of rTMS and the results from studies on both healthy volunteers and dysphagic patients. The clinical studies on dysphagia have primarily focussed on dysphagia post-stroke. We discuss why it is difficult to draw conclusions for the efficacy of this neurostimulation technique, given the major differences between studies. The intention here is to stimulate potential research questions not yet investigated for the application of rTMS on dysphagic patients prior to their translation into clinical practice for dysphagia rehabilitation.

An investigation into the strength of the association and agreement levels between subjective and objective sleep duration in adolescents.

STUDY OBJECTIVES: The majority of adolescent sleep research has utilized self-reported sleep duration and some have based information on a solitary question. Whilst some have claimed to have validated sleep survey data with objective actigraphy measures in adolescents, the statistical approach applied only demonstrates the strength of the association between subjective and objective sleep duration data and does not reflect if these different methods actually agree. METHODS: Data were collected as part of the Midlands Adolescents Schools Sleep Education Study (MASSES). Adolescents (n=225) aged 11-13 years provided estimates for weekday, weekend and combined sleep duration based on self-reported survey data, a 7-day sleep diary, and wrist-worn actigraphy. RESULTS: We assessed the strength of the relationship as well as agreement levels between subjective and objectively determined sleep duration (weekday, weekend and combined). Subjective diary sleep duration was significantly correlated with actigraphy estimates for weekday and weekend sleep duration r=0.30, p ≤ 0.001 and r=0.31, p ≤ 0.001 respectively. Pitman's test demonstrated no significant difference in the variance between weekend sleep duration (r=0.09, p=0.16) and combined sleep duration (r=0.12, p=0.08) indicating acceptable agreement between actigraphy and sleep diary sleep duration only. Self-reported sleep duration estimates (weekday, weekend and combined) did not agree with actigraphy determined sleep duration. CONCLUSIONS: Sleep diaries are a cost-effective alternative to survey/questionnaire data. Self-reported measures of sleep duration in adolescents do not agree with actigraphy measures and should be avoided where possible. Previous adolescent sleep studies that have utilized self-reported survey data may not provide a complete representation of sleep on the outcome measure of interest.