Acceptability, Accuracy and Safety of Disposable Transnasal Capsule Endoscopy for Barrett’s Esophagus Screening

BACKGROUND & AIMS: Screening for Barrett's esophagus (BE) with conventional esophagogastroduodenoscopy (C-EGD) is expensive. We assessed the performance of a clinic-based, single use transnasal capsule endoscope (EG Scan II) for the detection of BE, compared to C-EGD as the reference standard. METHODS: We performed a prospective multicenter cohort study of patients with and without BE recruited from 3 referral centers (1 in the United States and 2 in the United Kingdom). Of 200 consenting participants, 178 (89%) completed both procedures (11% failed EG Scan due to the inability to intubate the nasopharynx). The mean age of participants was 57.9 years and 67% were male. The prevalence of BE was 53%. All subjects underwent the 2 procedures on the same day, performed by blinded endoscopists. Patients completed preference and validated tolerability (10-point visual analogue scale [VAS]) questionnaires within 14 days of the procedures. RESULTS: A higher proportion of patients preferred the EG Scan (54.2%) vs the C-EGD (16.7%) (P<.001) and the EG Scan had a higher VAS score (7.2) vs the C-EGD (6.4) (P=.0004). No serious adverse events occurred. The EG Scan identified any length BE with a sensitivity value of 0.90 (95% CI, 0.83-0.96) and a specificity value of 0.91 (95% CI, 0.82-0.96). The EG Scan identified long segment BE with a sensitivity value of 0.95 and short segment BE with a sensitivity values of 0.87. CONCLUSION: In a prospective study, we found the EG Scan to be safe and to detect BE with higher than 90% sensitivity and specificity. A higher proportion of patients preferred the EG Scan to C-EGD. This device might be used as a clinic-based tool to screen populations at risk for BE. ISRCTN registry identifier: 70595405; ClinicalTrials.gov no: NCT02066233

Metabolic Syndrome and Cardiovascular Disease after Hematopoietic Cell Transplantation: Screening and Preventive Practice Recommendations from the CIBMTR and EBMT

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all-cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with an estimated prevalence of MetS of 31% to 49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to review literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors

Application of the NaWaTech Safety and O&M Planning Approach Re-Use Oriented Wastewater Treatment Lines at the Ordnance Factory Ambajhari, Nagpur, India

Not only due to a lack of infrastructure such as treatment plants, but also because the majority of existing treatment plants are showing poor or very poor operating conditions and fail to meet their performance targets, India faces increas-ing water shortage and degradation of fresh water resources. The paper gives an overview on the methodology of a safety and O&M (operation and maintenance) planning approach developed and implemented for supporting sustainable long- term operation of wastewater treatment systems. The implementation of the meth-odology is shown for the pilot installation at Ordnance Factory Ambajhari, Nagpur, India. At this site, two treatment lines have been installed: Line 1 is designed for 100 m 3 /day and comprises anaerobic pre-treatment, a vertical upfl ow constructed wetland, followed by a disinfection step, line 2 designed for 8 m 3 /day is a 2-stage French Reed Bed system. The effl uent of the French Reed Bed system is used for irrigation of a Short Rotation Plantation. The safety and O&M planning approach was used to identify critical O&M tasks, develop site-specifi c trainings of operators as well as a basis to develop the O&M manual and materials for operators (such as check-lists, etc.)

Assessing the Value of Echocardiograms for Patients with Acute Myeloid Leukemia (AML) Receiving Anthracyclines

Abstract Background AML is a life-threatening disease that requires prompt administration of anthracycline-based induction chemotherapy, particularly in younger adults. Prior to treatment initiation, patients (pts) undergo routine echocardiography (echo) screening to assess cardiac ejection fraction (EF) as a measure of induction tolerability, despite American Society of Clinical Oncology and National Comprehensive Cancer Center guidelines which state that only pts with prior cardiac disease or exposure to cardiotoxic drugs or radiation therapy require such evaluation This is costly to the health-care system and may be unnecessary. In this study, we assess whether the use of echo prior to anthracycline-based therapy in AML has a major effect on pt outcomes. Methods We reviewed clinical data on AML pts treated with anthracycline-based induction chemotherapy regimens at our institution from 2002-2014. EF was obtained by 2D echo prior to induction chemotherapy initiation. Charlson comorbidity index was used to evaluate comorbidities prior to therapy. A cox proportional hazard model was used to analyze the impact of baseline echo on overall survival, with p-values <.05 denoting significance. Results: Of the 120 pts included, 60 (50%) were female. At diagnosis, median age was 57 years (range, 23-85), white blood cell count (WBC) 8.9 x 109/L (0.3-227), hemoglobin 9.1g/dL (4.7-13.8), platelets 85 x 103 (8-277), bone marrow blasts 48% (14-95%). Cytogenetic risk categories per CALGB 8461 criteria: 12 pts (10%) were favorable, 63 (53%) indeterminate, and 41 (34%) unfavorable. Charlson morbidity index was > 1 in 23 pts (19%) and 50 (38%) were current or former smokers. All pts received induction chemotherapy with either idarubicin (38%), daunorubicin (38%), or mitoxantrone (23%) combined with cytarabine (7+3). In 116 pts (97%), the baseline echo showed a left ventricular ejection fraction (LVEF) >50% (+/- 5). In the 4 remaining pts (3%), the EF was < 40%. In a multivariable analysis controlling for age, WBC, cytogenetic risk group, Charlson comorbidity index, and smoking exposure, LVEF was not associated with overall survival (HR 1.05 with 95% CI 0.99-1.12 and p=.09). Among the 4 pts with EF<40% (age 57-71 years), all received full dose anthracycline and only the 71-year-old patient experienced congestive heart failure during treatment. Six pts (5%) died during induction therapy (4 weeks) and none of these had an EF <40%. Conclusion Among AML pts who received anthracycline-based induction chemotherapy, results from echocardiography did not impact outcome in >99% in this cohort. It is not clear that echocardiography, particularly in younger pts, provides value, and may delay treatment initiation. Disclosures No relevant conflicts of interest to declare

Different Genomic Patterns in Patients with Primary Acute Myeloid Leukemia (AML) Compared to Secondary AML in Patients with Normal Karyotype

Abstract Background For decades, cytogenetic analysis has played an essential role in AML risk stratification. Among the 50% of AML patients (pts) with normal karyotype (NK), outcome can vary widely. More recently, whole genome sequencing (WGS) and whole exome sequencing (WES) have identified several recurrent mutations that play an important role in AML pathogenesis and impact outcome. Pts with secondary AML (sAML) have a particularly poor prognosis, are not as responsive to standard induction chemotherapy, and often are referred in first complete remission to hematopoietic stem cell transplantation. We hypothesized that different genomic patterns exist between primary AML (pAML) and sAML that can distinguish the two, and can alter treatment recommendations. To negate the impact of chromosomal abnormalities, we focused our analyses on pts with NK. Methods We performed WES and multi-amplicon targeted deep sequencing on samples from bone marrow and peripheral blood of pts diagnosed with sAML at our institution between 1/2003- 1/2013 and who had NK cytogenetics. We compared them to pts with NK primary AML (pAML) whose data were extracted from The Cancer Genome Atlas (TCGA). A panel of 62 gene mutations that has been described as recurrent mutations in myeloid malignancies was included. Mutations were considered individually and grouped based on their functional pathways: RNA splicing (SF3B1, U2AF1/2, SRSF2, ZRSR2), DNA methylation (TET2, DNMT3A, IDH1/2), chromatin modification (ASXL1, EZH2, MLL, SUZ12, KDM6A), transcription (RUNX1, CEBPA, NPM1, BCOR/BCORL1, SETBP1, ETV6), activating signaling (FLT3, JAK2), cohesion (STAG2, SMC3, RAD21), RAS superfamily (K/NRAS, NF1, PTPN11, CBL) and tumor suppressor genes (TP53, APC, WT1, PHF6). Using deep sequencing methodology for resequencing or targeted sequencing, variant allelic frequency (VAF) was measured for each mutation detected. VAF was adjusted by zygosity evaluated by SNP-array karyotyping. For confirmation of clonal architecture, serial sample sequencing and single colony PCR were applied. Differences were compared using Fisher-exact test and Mann-Whitney U test for categorical and continues variables respectively. Results: Of 143 pts included, 101 (71%) had pAML and 42 (29%) had sAML. Compared to pAML, sAML pts were older (59 vs 69 years, p <.001), and had lower white blood cell count (28 vs 3.5 X 109/L, p <.001). Median hemoglobin (10 vs 10) g/dl and platelet counts (57 vs 60) k/uL were similar between the two groups. With a median follow up of 26.4 months (mo, range, .93-95.4), median OS was shorter for sAML than for pAML (12.9 vs 16.2 mo, p= .03). Overall, the most common mutations were: NPM1 (35%), DNMT3A (27%), FLT3 (25%), RUNX1 (14%), IDH1 (12%), IDH2 (12%), STAG2 (12%), TET2 (11%), NRAS (8%), ASXL1 (8%), U2AF1 (8%), PTPN11 (7%), WT1 (6%), BCOR (5%), and PHF6 (5%). Mutations in SF3B1, U2AF1/2, BCOR/BCORL1, ETV6, ASXL1, JAK2, STAG2, and APC were more common in sAML compared to pAML, whereas mutations in DNMT3A, NPM1, CEBPA, and FLT3 were more common in pAML. Mutations in activated pathways in splicing machinery, transcription, chromatin modification, cohesion and RAS pathway were more prominent in sAML, while mutations in DNA methylation and signaling pathways occurred more frequently in pAML. Serial sample analyses at multiple time points demonstrated intra-tumor heterogeneity in most cases of sAML, which was supported by additional cross sectional analyses of VAF in multiple gene mutations in each case. These findings prompted us to evaluate secondary events in the cohort of pts whose sAML originated from an initial MDS stage, defined by ancestral mutations. Among genes frequently affected by mutations, TET2 and ASXL1 were identified as founder events, whereas STAG2, NRAS and PTPN11 were observed in subclonal sAML derived from founder MDS clones. In pAML, however, TET2 and ASXL1 mutations were found to be secondary lesions, while IDH1 and DNMT3A were identified as ancestral events. Conclusion Clear genomic variations exist between sAML and pAML that suggest differences in the pathophysiology of both diseases. Specific therapies should be directed to the activated pathways according to the unique clonal hierarchy in each AML subtype. Disclosures No relevant conflicts of interest to declare