Citations

182 Background: The purpose of this study was to examine the associations of three different measures of anxiety and depression with patient reported distress (PRD) level and survival after radiotherapy (RT). Methods: 518 patients who underwent RT between 2012 and 2016 were included in this retrospective study. PRD was assessed at the time of RT using the NCCN thermometer and a 30 question survey of distress related items. PRD and clinical and demographic data was retrospectively collected and analyzed. The three measures this study focused on that assessed patient anxiety and depression involved asking patients about their level of concern regarding feeling down, regarding loss of interest, and regarding feeling nervous. Associations between baseline patient characteristics and survival after start of RT were evaluated using single variable Cox proportional hazards regression models. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. Associations of level of concern regarding patient anxiety/depression with survival after RT were evaluated using single variable and multivariable Cox proportional hazards regression models. Results: Overall, PRD level and concern regarding anxiety/depression were positively correlated (p < 0.001). Additionally, there was a significant association between level of concern regarding feeling down and palliative patients (p = 0.03). There was also a significant association between level of concern regarding loss of interest and palliative patients (p = 0.03), with level of concern highest for thorax, breast, and head and neck. There was also a significant different between level of concern regarding feeling nervous and gender (p = 0.05). There was not a significant difference between any of the three measures and survival after RT (all p ≥ 0.21). Conclusions: Anxiety and depression in patients receiving palliative and curative RT was associated with overall distress. Baseline screening of PRD may identify patients who would benefit from intervention to address the causes of their underlying anxiety and depression.

Objective Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions These data suggest several plausible genetic links between DLBCL and SLE.

AbstractLinear morphea of the limb primarily affects children, and extracutaneous manifestations are common. Orthopedic surgeons are often essential in the care of patients with linear morphea, yet there are few reports outlining specific orthopedic complications in this population. We sought to improve the understanding of orthopedic complications in linear morphea of the limb. Between 1999 and 2014, 51 children were evaluated for linear morphea of an extremity. Twenty‐six (51%) had documented orthopedic manifestations. Outcome measures included limb length discrepancy, angular malalignment, limb atrophy, and orthopedic surgical intervention. Joint contractures were most common, affecting 88% of patients, followed by limb atrophy, angular deformity, and limb length discrepancy; 14% required surgical intervention. Despite the use of systemic immunosuppressive therapy in many patients, approximately half of patients with linear morphea of an extremity have orthopedic disease. Early orthopedist involvement is crucial to improve limb alignment and preserve function.

Abstract Glioblastoma is the most frequent primary brain tumor in adults and a highly lethal malignancy with a median survival of about 15 months. The aggressive invasion of the surrounding normal brain makes complete surgical resection impossible, increases the resistance to radiation and chemotherapy, and assures tumor recurrence. Thus, there is an urgent need to develop innovative therapeutics to target the invasive tumor cells for improved treatment outcomes of this disease. Expression of TROY (TNFRSF19), a member of the tumor necrosis factor (TNF) receptor family, increases with increasing glial tumor grade and inversely correlates with patient survival. Increased expression of TROY stimulates glioblastoma cell invasion in vitro and in vivo and increases resistance to temozolomide and radiation therapy. Conversely, silencing TROY expression inhibits glioblastoma cell invasion, increases temozolomide sensitivity, and prolongs survival in an intracranial xenograft model. Here, a novel complex is identified between TROY and EGFR, which is mediated predominantly by the cysteine-rich CRD3 domain of TROY. Glioblastoma tumors with elevated TROY expression have a statistically positive correlation with increased EGFR expression. TROY expression significantly increases the capacity of EGF to stimulate glioblastoma cell invasion, whereas depletion of TROY expression blocks EGF stimulation of glioblastoma cell invasion. Mechanistically, TROY expression modulates EGFR signaling by facilitating EGFR activation and delaying EGFR receptor internalization. Moreover, the association of EGFR with TROY increases TROY-induced NF-κB activation. These findings substantiate a critical role for the TROY–EGFR complex in regulation of glioblastoma cell invasion. Implications: The TROY–EGFR signaling complex emerges as a potential therapeutic target to inhibit glioblastoma cell invasion. Mol Cancer Res; 16(2); 322–32. ©2017 AACR.

Highly specialized left ventricular assist device care is not readily available in many areas, potentially limiting access to therapy. This retrospective analysis examines the relationship of outcomes by patient distance from implanting left ventricular assist device center within the Mechanical Circulatory Support Research Network. Zip codes were used to calculate patient distance, with the primary outcome of interest being 3-year survival by distance from the surgical center. Secondary outcomes included 90-day survival and incident event rates for the following: gastrointestinal bleeding, infection, cerebral event, and pump thrombosis. Across the four centers, there were 1184 patients supported for a median of 486 days. Overall survival was 91 ± 0.8% at 90 days and 61 ± 1.9% at 3 years, with worse 3-year survival in those living >90 vs . ≤90 miles from the ventricular assist device implant center (55 ± 3.0% vs . 64 ± 2.5, p = 0.019). Patients living >90 miles from an implant center were older, more likely to be implanted for destination therapy support, had a prior sternotomy, and had worse renal function than those living closer ( p <0.05 for all). After adjusting for these factors, albumin and center of implant, the hazard ratio did not reach statistical significance (hazard ratio = 1.2; p = 0.14). Except for gastrointestinal bleeding, the event rates for the secondary outcomes were higher for those living closer to the implanting center. Protocols should be designed for more frequent follow-up and increased shared care opportunities to ensure optimal outcomes are achieved in distant patients.

The Institute of Medicine and US Food and Drug Administration (FDA) recognize that activating clinical trials in the United States is lengthy and inefficient. Downstream consequences include increased expense, suboptimal accrual, move of clinical trials overseas, and delayed availability of treatments for patients. An in‐tandem processing initiative is here highlighted that transformed the activation of clinical trials (TACT), reduced the activation time by 70%, and offers a paradigm for enhanced translational readiness.

SummaryDue to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country‐specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.

SummaryFactors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV‐related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high‐treatment rate will contribute to a reduction in total cases and HCV‐related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV‐related morbidity and mortality.