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AbstractBackgroundMost research on family impacts of paediatric chronic pain has been conducted with mothers, and therefore, little is known about fathers' adjustment. However, it is well established that caring for a child with chronic pain takes a toll on caregiver well‐being. Parents of children with chronic pain have been found to experience high levels of anxiety, depression, and parenting stress. As such, the goal of this study was to examine differences between mothers and fathers of youth with chronic pain, explore interaction effects between parent gender and child variables, and compare parents' scores to national norms.MethodsParticipants included 160 matched mothers and fathers of youth with chronic pain participating in an interdisciplinary pain rehabilitation programme. At admission, parents completed the Center for Epidemiological Studies–Depression scale and SF‐36 to assess depression and health‐related quality of life. T tests and analysis of variance were used to explore differences between mothers and fathers and population norms.ResultsMothers reported experiencing significantly poorer functioning than did fathers in the domains of emotional role interference, social functioning, and vitality. Differences remained significant when controlling for other psychosocial variables using multiple regression. Child gender and depression level were found to be significant predictors of parent mental health, with mothers' mental health more negatively influenced by child depression. Additionally, mothers' scores in mental health domains were significantly lower than population norms.ConclusionsThese findings highlight the importance of identifying the ways in which chronic pain in youth may affect parents differently in order to enhance caregiver support and interventions.

AbstractBackgroundOncological outcomes of locally advanced rectal cancer depend on the quality of surgical and oncological management. Enhanced recovery pathways (ERPs) have yet to be assessed for their oncological impact when used in combination with minimally invasive surgery. This study assessed outcomes with or without an ERP in patients with rectal cancer.MethodsThis was a retrospective analysis of all consecutive adult patients who underwent elective minimally invasive surgery for primary rectal adenocarcinoma with curative intent between February 2005 and April 2018. Both laparoscopic and robotic procedures were included. Short-term morbidity and overall survival were compared between patients treated according to the institutional ERP and those who received conventional care.ResultsA total of 600 patients underwent minimally invasive surgery, of whom 320 (53·3 per cent) were treated according to the ERP and 280 (46·7 per cent) received conventional care. ERP was associated with less overall morbidity (34·7 versus 54·3 per cent; P < 0·001). Patients in the ERP group had improved overall survival on univariable (91·4 versus 81·7 per cent at 5 years; hazard ratio (HR) 0·53, 95 per cent c.i. 0·28 to 0·99) but not multivariable (HR 0·78, 0·41 to 1·50) analysis. Multivariable analysis revealed age (HR 1·46, 1·17 to 1·82), male sex (HR 1·98, 1·05 to 3·70) and complications (HR 2·23, 1·30 to 3·83) as independent risk factors for compromised overall survival. Disease-free survival was comparable for patients who had ERP or conventional treatment (80·5 versus 84·6 per cent at 5 years respectively; P = 0·272).ConclusionTreatment within an ERP was associated with a lower morbidity risk that may have had a subtle impact on overall but not disease-specific survival.

TPS679 Background: AA has re-emerged as a promising anti-cancer agent based on recent knowledge of pharmacokinetics, discovery of unexpected mechanisms of action, and early phase trials with IV AA.(Shenoy et al, Cancer Cell 34: 2018, in press) We hypothesized that ccRCC would be particularly susceptible to anti-cancer effects of IV AA due to: a. TET dependent demethylation of the hypermethylated genome of ccRCC causing re-expression of tumor suppressors (Shenoy et al, AACR 2018 Targeting DNA methylation conf. A11; Hu et al, Clin Cancer Res 20:4349-60, 2014) b. H2O2 production causing intra-tumoral oxidative damage, hypothesized to be enhanced by high iron content in RCC microenvironment c. Intracellular accumulation of dehydroascorbic acid secondary to high HIF activity in ccRCC. Animal data and case reports support the hypothesis. Methods: Trial design: Patients (pts) with newly diagnosed metastatic/ unresectable ccRCC are randomized 1:1 to arm A (pazopanib 800 mg/d plus IV AA 1g/kg 3 times/week) or arm B (pazopanib 800 mg/d). Protocol treatment is for 10 cycles (unless PD, unacceptable AE, alternative therapy, or pt refusal), each cycle being 28 days. Primary endpoint is Treatment Failure-Free rate at 40 weeks (TFF40). Treatment Failure is defined as: Radiographic disease progression, off-protocol treatment due to AE, alternative therapy initiation (except metastasectomy post clinical benefit), or death. Secondary endpoints include OS, PFS, ORR and AE. Statistical methods: 82 eligible pts (41 in each in arm) will provide 81% power to detect a 19% increase of TFF40 from 45% in arm B to 64% in arm A assuming a one-sided type I error rate of 0.19 (EAST 6.4). Correlatives: Epigenetic mechanism: 5mC, 5hmC and H3K27me3 IHC, MeDIP/ hMeDIP seq, RNA seq. H2O2 mechanism: tumor microenvironment iron, tumor catalase IHC. Dehydroascorbic acid mechanism: HIF-1 alpha, HIF-2 alpha, GLUT-1 IHC. Key exclusion criteria: G6PD deficiency, renal disease (Cockcroft Gault CrCl < 55 ml/min). ClinicalTrials.gov Identifier: NCT03334409 Status: Open for accrual in 9/10 planned sites. Funding Source: Foundation. Clinical trial information: NCT03334409.

The lymphocyte crossmatch is currently the only cell‐based compatibility assay performed by histocompatibility laboratories for transplant purposes. While in many transplant programs the complement‐dependent cytotoxicity crossmatch (CDCXM) remains in use, when available, the flow cytometry crossmatch (FCXM) is the method of choice because of its superior sensitivity and specificity. Unfortunately, the maintenance and cost of a flow cytometer is a considerable limitation for small histocompatibility laboratories. Therefore, in this study, we evaluated the use of the Cellometer Vision CBA image cytometer (Nexcelom Bioscience LLC, Lawrence, Massachusetts) as an alternative instrument to perform the crossmatch assay. The 3‐color FCXM protocol was modified into two separate 2‐color panel image cytometry crossmatches (IXMs), one for T cells and one for B cells. After initial serum and cell incubation, a cocktail consisting of PE/Cy5‐conjugated anti‐human CD3 or CD19 and PE‐conjugated anti‐human IgG F(ab′)2was added to the T cell and B cell panels, respectively. The final cell preparation was added to a separate counting chamber. Images were captured using the Cellometer Vision CBA, an image cytometer designed for cell counting, size analysis and fluorescence intensity measurement. Thirty‐nine IXMs were performed and compared with the FCXM. We obtained a concordance sensitivity of 94.1% and 100% and specificity of 100% and 88.9% for T cells and B cells, respectively. The linearity of the system was verified using dilutions of a sample containing known donor‐specific anti‐HLA antibodies (DSA) against the target cells. This feasibility study demonstrates that the FCXM test could be easily adapted to the Cellometer Vision CBA image cytometer without compromising specificity and sensitivity. The low instrumentation cost, minimal maintenance, and simple operation allow for efficient implementation or transition from the FCXM to the IXM method.

OBJECTIVEThe role of CT perfusion (CTP) in the management of patients with acute ischemic stroke (AIS) remains a matter of debate. The primary aim of this study was to evaluate the correlation between the areas of infarction and penumbra on CTP scans and functional outcome in patients with AIS.METHODSThis was a retrospective review of 100 consecutively treated patients with acute anterior circulation ischemic stroke who underwent CT angiography (CTA) and CTP at admission between February 2011 and October 2014. On CTP, the volume of ischemic core and penumbra was measured using the Alberta Stroke Program Early CT Score (ASPECTS). CTA findings were also noted, including the site of occlusion and regional leptomeningeal collateral (rLMC) score. Functional outcome was defined by modified Rankin Scale (mRS) score obtained at discharge. Associations of CTP and CTA parameters with mRS scores at discharge were assessed using multivariable proportional odds logistic regression models.RESULTSThe median age was 67 years (range 19–95 years), and the median NIH Stroke Scale score was 16 (range 2–35). In a multivariable analysis adjusting for potential confounding variables, having an infarct on CTP scans in the following regions was associated with a worse mRS score at discharge: insula ribbon (p = 0.043), perisylvian fissure (p < 0.001), motor strip (p = 0.007), M2 (p < 0.001), and M5 (p = 0.023). A worse mRS score at discharge was more common in patients with a greater volume of infarct core (p = 0.024) and less common in patients with a greater rLMC score (p = 0.004).CONCLUSIONSThe results of this study provide evidence that several CTP parameters are independent predictors of functional outcome in patients with AIS and have potential to identify those patients most likely to benefit from reperfusion therapy in the treatment of AIS.