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The immune system has the ability to recognize and specifically reject tumors, and tumors only become clinically apparent once they have evaded immune destruction by creating an immunosuppressive tumor microenvironment. Radiotherapy (RT) can cause immunogenic tumor cell death resulting in cross-priming of tumor-specific T-cells, acting as an in situ tumor vaccine; however, RT alone rarely induces effective anti-tumor immunity resulting in systemic tumor rejection. Immunotherapy can complement RT to help overcome tumor-induced immune suppression, as demonstrated in pre-clinical tumor models. Here, we provide the rationale for combinations of different immunotherapies and RT, and review the pre-clinical and emerging clinical evidence for these combinations in the treatment of cancer.

The mortality rate for infants awaiting a heart transplant is 40% because of the extremely limited number of donor organs. Ventricular assist devices (VADs), a common bridge-to-transplant solution in adults, are becoming a viable option for pediatric patients. A major obstacle faced by VAD designers is thromboembolism. Previous studies have shown that the interrelated flow characteristics necessary for the prevention of thrombosis in a pulsatile VAD are a strong inlet jet, a late diastolic recirculating flow, and a wall shear rate greater than 500 s(-1). Particle image velocimetry was used to compare the flow fields in the chamber of the 12 cc Penn State pediatric pulsatile VAD using two mechanical heart valves: Bjork-Shiley monostrut (BSM) tilting disk valves and CarboMedics (CM) bileaflet valves. In conjunction with the flow evaluation, wall shear data were calculated and analyzed to help quantify wall washing. The major orifice inlet jet of the device containing BSM valves was more intense, which led to better recirculation and wall washing than the three jets produced by the CM valves. Regurgitation through the CM valve served as a significant hindrance to the development of the rotational flow.

(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014) was conducted. The medical subject heading (MeSH) terms used in the search included: "neurosurgery" OR "neurosurgical procedure," "brain neoplasms," "infarction" and "decompression," "carotid stenosis," "cerebral hemorrhage," and "spinal fusion." These studies were limited to RCTs, in humans, and in the English language. The Consolidated Standards for Reporting of Trials (CONSORT) and Jadad scales were used to assess the quality of RCT design and reporting. The standardized median times cited (median citations divided by years since publication) were used to assess impact. A pragmatic-explanatory continuum indicator summary-based scale was used to assess the design of the studies as primarily pragmatic or explanatory. results Sixty-one articles were identified, and the following subspecialties were the most common: vascular (23, 37%), followed by functional neurosurgery and neurooncology (both 13, 21%). The following nations were the primary leaders in RCTs: US (25 studies, 41%), Germany (8 studies, 13%), and the United Kingdom (7 studies, 11%). Median sample size was 100 (interquartile range [IQR] 41.5-279). The majority of the studies (40, 66%) had pragmatic objectives. The median number of times cited overall was 69 . The combined median CONSORT score was 36 (IQR 27.5-39). Blinding was most deficiently reported. Other areas with a relatively low quality of reporting were sample size calculation (34.2% of surgical, 38.5% of drug, and 20% of device studies), allocation concealment (28.9% of surgical, 23.1% of drug, and 50% of device studies), and protocol implementation (18.4% of surgical, 23% of drug, and 20% of device studies). The quality of reporting did not correlate with the study impact. All studies had a median Jadad score ≤ 3. Thirty-three pragmatic studies (83%) and 5 explanatory studies (25%) met the design objectives. All pragmatic studies based on drug and device trials met their objectives, while 74% of pragmatic surgical trials met their objectives. coNclusioNs The prevalence of neurosurgical RCTs is low. The quality of RCT design and reporting in neurosurgery is also low. Many study designs are not compatible with stated objectives. Pragmatic studies were more likely to meet design objectives. Given the role of RCTs as one of the highest levels of evidence, it is critical to improve on their methodology and reporting.

The objectives for the treatment of Wilms tumor in both the Children's Oncology Group (COG) and the International Society of Paediatric Oncology (SIOP) have focused on improving cure rates and minimizing toxicity by limiting the use of radiation and doxorubicin. Although the timing of surgery is different in COG (upfront surgery) and SIOP (upfront chemotherapy with delayed surgery), both are effective strategies and have the same survival. Fewer patients are treated with radiotherapy in the SIOP trials but with higher doses. The prognostic significance of biological markers such as 1q gain and clinical outcomes with novel radiation techniques such as intensity modulated radiation therapy will be determined in upcoming clinical trials. A closer collaboration between COG and SIOP could help promote research and improve the clinical outcomes of children with Wilms tumor.

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Background-A survey of overnight oximetry was conducted to estimate the prevalence of nocturnal hypoxaemia in patients with cryptogenic fibrosing alveolitis and to establish whether nocturnal hypoxaemia is related to quality of life. Methods-All patients with cryptogenic fibrosing alveolitis attending Nottingham City Hospital were invited to enter the study. Spirometric measurements and capillary blood gas tensions were obtained and overnight oxygen saturation was recorded at home. Quality of life was assessed using the Short Form-36, Chronic Respiratory Questionnaire, Hospital Anxiety Depression Scale, and Epworth Sleepiness Score questionnaires. Results-Sixty seven eligible patients were identified and 50 agreed to enter the study, although two were subsequently excluded because they already used oxygen overnight. In the remaining 48 the mean (SD) overnight oxygen saturation (SaO 2 ) was 92.5 (4.3)% and the median number of dips greater than 4% per hour was 2.3 (interquartile range 1.5-5.3). Daytime oxygen level predicted mean overnight SaO 2 (1.94%/kPa, 95% CI 1.22 to 2.66, p<0.001) but percentage predicted forced vital capacity (FVC) did not (0.018%/% predicted FVC, 95% CI -0.04 to 0.08, p=0.5). Nocturnal hypoxaemia was associated with decreased energy levels and impaired daytime social and physical functioning, and these eVects were independent of FVC. Conclusions-Nocturnal hypoxaemia is common in patients with cryptogenic fibrosing alveolitis and may have an impact on health related quality of life. (Thorax 2001;56:482-486)

Ventricular assist devices (VADs) have become a viable option for adult patients with end-stage heart failure during the bridge-to-transplant period and have recently shown promise in aiding in myocardial recovery. Because the number of available organs is insufficient, mechanical circulatory support systems such as VADs are also being developed for use in pediatric patients. During myocardial recovery, the system must be weaned from the patient to prepare for explant; for pulsatile devices, this often includes a reduction in flow rate, which can change the fluid dynamics of the device. These changes in flow need to be monitored because strong diastolic rotational flow, no areas of blood stasis, low blood residence time, and wall shear rates above 500 s, can help prevent thrombus deposition. Particle image velocimetry was used to observe the planar flow patterns and wall shear rates of the 12 cc Penn State Pneumatic Pediatric VAD (PVAD) at a normal operating condition and a reduced beat rate. At the reduced beat rate, the PVAD showed an earlier loss of rotational pattern, increased blood residence time, and an overall reduction in wall shear rate at the outer walls. Because this reduction in flow rate could lead to a possible increase in thrombus deposition, it may be necessary to look into other options for weaning a patient from the PVAD.