Citations

Abstract The amplified MYCN gene serves as an oncogenic driver in approximately 20% of high-risk pediatric neuroblastomas. Here we show that MYC itself is a potent transforming gene in a separate subset of high-risk neuroblastoma cases (~10%), based on (i) its upregulation by focal enhancer amplification or genomic rearrangements leading to enhancer hijacking, and (ii) its ability to transform neuroblastoma precursor cells in a transgenic animal model. The aberrant regulatory elements associated with oncogenic MYC activation include focally amplified distal enhancers or translocation of highly active enhancers from other genes to within topologically associating domains containing the MYC gene locus. The clinical outcome for patients with high levels of MYC expression is virtually identical to that of patients with amplification of the MYCN gene, a known high-risk feature of this disease. Together, these findings establish MYC as a bona fide oncogene in a clinically significant group of high-risk childhood neuroblastomas. Citation Format: Mark W. Zimmerman, Yu Liu, Shuning He, Adam D. Durbin, Brian J. Abraham, John Easton, Ying Shao, Beisi Xu, Shizhen Zhu, Xiaoling Zhang, Nina Weichert-Leahey, Richard A. Young, Jinghui Zhang, A. Thomas Look. MYC activation through enhancer hijacking or focal enhancer amplification drives a subset of high-risk pediatric neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr IA19.

Objectives. To assess whether there are shared exposures associated with Sjogren’s syndrome (SS), dry eye syndrome (DES), and B-cell non-Hodgkin lymphoma (B-NHL), in order to determine whether they are etiologically related. Methods. In a clinic-based case-control study, 702 participants (91 SS, 120 DES, 211 (age and sex frequency-matched) controls, and 280 B-NHL cases) were recruited and interviewed regarding exposures, medical history, and family history. Results. Female predominance was noted in SS (ratio 9.2 : 1). Eye dryness was severest in SS compared to DES and controls (P<0.001). Compared to controls, alcohol consumption was inversely associated with NHL, DES, and SS (odds ratio OR=0.47, 95% confidence interval (CI): 0.31-0.71; OR=0.54, 95% CI: 0.33-0.88; and OR=0.26, 95% CI: 0.14-0.49, respectively), while a previous history of infection requiring hospitalization was positively associated with all three conditions: NHL (OR=1.92; 95% CI: 1.23-2.99), DES (OR=3.29; 95% CI: 1.97-5.47), and SS (OR=4.74; 95% CI: 2.66-8.44). NHL patients were more likely to report first-degree relatives with hematologic cancer, while having first-degree relatives with an autoimmune disease (AID) was associated with SS (OR=5.25; 95% CI: 2.59-10.63) and DES (OR=3.55; 95% CI: 1.83-6.91) compared to controls. Conclusions. Some exposures are associated with all three conditions (such as an inverse association with alcohol consumption and a positive association with serious past infection), while a family history of AID appears to be shared by DES and SS, but not NHL subjects. Shared risk factors for all three conditions indicate possible mutual etiological pathways.

BACKGROUND: An increasing proportion of pediatric hospital days are attributed to technology-dependent children. The impact that a pediatric home care nursing (HCN) shortage has on increasing length of hospital stay and readmissions in this population is not well documented. METHODS: We conducted a 12-month multisite prospective study of children with medical complexity discharging with home health. We studied the following 2 cohorts: new patients discharging for the first time to home nursing and existing patients discharging from the hospital to previously established home nursing. A modified delay tool was used to categorize causes, delayed discharge (DD) days, and unplanned 90-day readmissions. RESULTS: DD occurred in 68.5% of 54 new patients and 9.2% of 131 existing patients. Lack of HCN was the most frequent cause of DD, increasing costs and directly accounting for an average length of stay increase of 53.9 days (range: 4–204) and 35.7 days (3–63) for new and existing patients, respectively. Of 1582 DDs, 1454 (91.9%) were directly attributed to lack of HCN availability. DD was associated with younger age and tracheostomy. Unplanned 90-day readmissions were due to medical setbacks (96.7% of cases) and occurred in 53.7% and 45.0% of new and existing patients, respectively. CONCLUSIONS: DD and related costs are primarily associated with shortage of HCN and predominantly affect patients new to HCN. Medical setbacks are the most common causes of unplanned 90-day readmissions. Increasing the availability of home care nurses or postacute care facilities could reduce costly hospital length of stay.

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.

Abstract Background and aims Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is challenging to live with, often accompanied by pervasive fatigue and pain, accompanied by decreased quality of life (QoL) as well as anxiety and/or depression. Associations between higher pain, lower QoL and higher anxiety and depression have been shown in patients with various chronic pain disorders. Few studies have however examined such associations in a sample of patients with ME/CFS. The aims of the current study were to examine the impact of pain levels and compare levels of pain, health related QoL, anxiety and depression between patients with ME/CFS and healthy controls. In addition, the study aimed and to examine these relationships within the patient group only. Methods This is a cross-sectional questionnaire based study comparing 87 well-diagnosed patients with ME/CFS with 94 healthy controls. The De Paul Symptom Questionnaire (DSQ), the Medical Outcomes Study Short-Form Surveys (SF-36) and the Hospital Anxiety and Depression Scale (HADS) were used to examine and compare pain, physical function, QoL, anxiety and depression in patients and healthy controls. Further the pain variables were divided into pain total, pain intensity and a pain frequency score for analyses of the above mentioned variables within the patient group only. Results Significantly higher levels of pain, anxiety and depression, and lower levels of QoL were found in the patient group compared with healthy controls. For the patient group alone, pain was significantly associated with lower QoL in terms of physical functioning, bodily pain, general health functioning, vitality and social functioning capacity. In this patient sample, only frequency of joint pain showed significant difference in psychological variables such as depression and anxiety – depression combined. Conclusions ME/CFS patients differ significantly from healthy controls in pain, health related QoL, anxiety and depression. Pain is significantly associated with reduced QoL and overall a lower level of functioning. The relation between pain and anxiety and depression appears less clear. Implications Pain is for many ME/CFS patients associated with reduced physical functioning and reduced QoL. A thorough pain assessment can therefore be essential for clinicians, and subsequent medical pain treatment combined with good pain coping skills may increase functioning level and QoL for these patients. The link between joint pain and psychological factors should also be focused in clinical practice in terms of mapping and counseling. Pain should be further examined to understand the importance it may have for functioning level as reduced function is a main criteria when diagnosing the patients.

AbstractEnhanced recovery protocols consist of a bundle of concepts including early feeding, opioid‐sparing multimodal pain management, and euvolemia, with the overarching goal of hastening postoperative recovery. Enhanced recovery after surgery has been shown to reduce hospital length of stay, reduce costs, and decrease perioperative opioid requirements in benign and oncologic gynecologic surgery. Interventions without supporting evidence of benefit, such as the use of mechanical bowel preparation, routine use of nasogastric tubes and surgical drains, caloric restriction, routine use of intravenous opioid analgesics, and over‐vigorous intravenous hydration should be discouraged to improve broader endpoints such as patient satisfaction and overall recovery. Successful implementation requires engagement from a multidisciplinary team including surgeons, anesthesiologists, nurses, and pharmacists.

4007 Background: NRG/RTOG 0848 is a 2-step study designed to determine whether erlotinib (E) added to gemcitabine (G) (randomized Ph II) &/or adjuvant radiation with concurrent 5-FU or capecitabine following 6 months of systemic chemotherapy (Ph III), improve survival in patients (pts) with resected pancreatic head adenocarcinoma. The erlotinib results are reported here. Methods: Eligible pts include those with resected pancreatic head adenocarcinoma, pathologic stage T1-T3, N0-1, M0; PS 0-1, & CA19-9 ≤ 180 IU/L. Pts in Arms 1 & 2 received G 1 gm/m2 weekly for 3 weeks in a 28-day cycle for 6 cycles. Pts in Arm 2 also received E 100 mg/day. The primary hypothesis for the E portion was that G+E would increase overall survival (OS) compared to G alone. With a 1-sided alpha of 0.15, 200 OS events provide 80%/90% power to detect a signal for an increase in median OS from 22 to 28.8/30.6 months (mos). OS was estimated by the Kaplan-Meier method & arms compared using the log rank test. The Cox proportional hazards model was used to analyze treatment effect. Results: 336 pts were randomized from 11/17/2009 to 2/28/2014, with 163 pts evaluable for G and 159 for G+E. Median age was 63 years (39-86). Most pts had pathologic T3 disease (78%) & CA19-9 ≤ 90 (93%). There are 32 pts (20%) with grade 4 adverse events (AEs) & 2 pts (1%) with grade 5 AEs on G and 27 (17%) & 3 (2%) on G+E arm, respectively. There are fewer grade ≥ 3 GI AEs on the G arm (22%) as compared to the G+E arm (28%), and 110 (69.2%) & 93 (59.6%) pts received at least 85% of planned G dose for the G & G+E arms, respectively. 58% of E pts received at least 85% of planned E dose. The median follow-up for alive pts is 42.5 mos (min-max: < 1-75). With 203 deaths, median & 3-yr OS (95% CI) are 29.9 mos (21.7-33.4) & 39% (30, 45) for G and 28.1 mos (20.7-30.9) & 39% (31, 47) for G+E; log-rank p = 0.62. The hazard ratio (95% CI) comparing OS of G+E to G is 1.04 (0.79- 1.38). Conclusions: The addition of adjuvant E to G did not provide a signal for increased OS in pts with resected pancreatic head cancer compared to G alone. Accrual to the trial is continuing to answer the Ph III radiation question. Clinical trial information: NCT01013649.